PMID- 1493487 TI - "De-jargonizing" research communication. PMID- 1493488 TI - Intergenerational geriatric remotivation. AB - This piece of a larger study on intergenerational geriatric remotivation discusses influential program variables. Interviews, participant observation, and videotapes were used to study a program in the Southeast and a comparison program in the Midwest. The variables examined were frequency, longevity, and constancy of intergenerational contact, problem discovery and problem resolution procedures, physical environment, and activity structure. As practitioners contemplate establishing intergenerational programs, a number of issues regarding program structure need to be considered to ensure that outcomes match expectations. PMID- 1493489 TI - Cultural diversity in the nurse-client encounter. AB - This study examined encounters between nurses and clients who originate from diverse cultures to determine the perspectives of both the nurse and the client concerning the experience of their time spent together. Fifteen nurses and 15 clients were interviewed separately after their encounter, and their responses were compared. Three major themes emerged from the data: descriptions of mutual satisfaction with the encounter (mentioned most often), different or incongruent perceptions of the encounter, and mutual dissatisfaction with the encounter. Themes in the category of mutual satisfaction were markedly similar to the themes of caring described by previous research. Although there were expressions of language difficulties and lack of knowledge of cultural differences, these did not appear to inhibit the mutual caring that was described. PMID- 1493490 TI - A comparison of childbirth expectations in high-risk and low-risk pregnant women. AB - This study described and compared the childbirth expectations of high-risk and low-risk pregnant women and then examined the influence of anxiety, risk status, and childbirth preparation on these expectations. This descriptive correlational study employed a convenience sample of 75 high-risk nulliparas and 77 low-risk nulliparas. Results indicated that high-risk pregnant women had significantly less positive expectations for their childbirth experience than did low-risk pregnant women. In particular, high-risk pregnant women expected more medical intervention and more difficulty coping with pain during their labor and birth. For both groups of women, anxiety was negatively correlated with childbirth expectations, whereas childbirth preparation was positively correlated with childbirth expectations. PMID- 1493491 TI - Effects of intraoperative progress reports on anxiety of elective surgical patients' family members. AB - The purpose of this experimental study was to examine the effects of intraoperative progress reports on family members' state anxiety level (STAI S Anxiety), mean arterial pressure (MAP), and heart rate during elective surgical procedures. Family members of randomly selected surgical patients were eligible to participate. Control group family members (n = 50) received usual care. Family members in the experimental group (n = 50) received a 5- to 10-minute progress report protocol about halfway through a surgical procedure. Families' STAI S Anxiety scores, MAP, and heart rates were compared between the control and experimental groups using multivariate analysis of variance (MANOVA). Family members in the experimental group reported lower STAI S-Anxiety scores (p < .001), and had significantly lower MAP and heart rates than did the control group (p < .001). Progress reports appear to be a beneficial nursing intervention for reducing anxiety in family members during the intraoperative period. PMID- 1493492 TI - A comparative study of patients with chronic pain in India and the United States. AB - Pain is the most frequently reported symptom in the health care industry today. Chronic pain in the United States costs millions of dollars annually, and its financial impact is mounting. For individuals living in the United States, chronic pain affects nearly all normal activities and often leaves the person feeling helpless and hopeless. Literature supports the idea that chronic pain does not have the same debilitating effect in the Eastern cultures as it does in the Western cultures. Therefore, clients from both a Western and Eastern culture were studied. This qualitative research, based on grounded theory, sampled 20 persons from India and 20 from the United States. Focused, open-ended interviews were used as the major manner of gathering data. Although the condition of chronic pain was the same for each culture, there were significant differences regarding the phenomenon of chronic pain. This research indicates the need for health professionals to assess, implement a plan of care for, and evaluate patients' suffering and need for improved quality of life rather than focusing only on the elimination of pain. PMID- 1493493 TI - Home health care: delineation of research priorities and formation of a national network group. AB - The purposes of this national study were (a) to determine priority research questions in home health care nursing and (b) to develop a home health research network group. Collaborative brainstorming was used initially by an interdisciplinary research team to generate a list of research questions. The major content areas covered in the questionnaire were questions relating to home health care as a delivery system, patient classification, quality assurance, nursing diagnosis, and nursing professionalism. A survey of 450 practicing home health care nurses was completed. The questions were rated by the respondents on a scale of high, medium, or low research priority. The response rate was 52%, with home health nurses responding from 30 states. The results clearly indicated the top 10 research priorities for home health care nursing research. The formation of the home health care research network groups are also discussed. PMID- 1493495 TI - From QA to CQI and TQM. PMID- 1493494 TI - Recharge ... and keep on going. PMID- 1493496 TI - Designing a patient education system. PMID- 1493497 TI - Research. Starter library. PMID- 1493498 TI - Using learning contracts. PMID- 1493500 TI - Reaching the learner's learner. PMID- 1493499 TI - Streamlining orientation: 7 easy steps. PMID- 1493501 TI - High turnover? Try specialized SD. PMID- 1493502 TI - Stephen Brookfield on self-directed learning. PMID- 1493503 TI - Using educator expertise to enhance performance appraisal. PMID- 1493504 TI - [Free alveolar cells in experimental pulmonary emphysema. I. Statistical analysis of cellular composition and lung morphometry]. AB - The study was carried out on an experimental papain induced model of pulmonary emphysema. The authors assessed the cell populations sampled with lavage. Special emphasis was directed on alveolar macrophages and neutrophils. Extent of emphysema was analysed morphometrically. The authors demonstrated an influx of neutrophils 24 hours after papain was introduced intratracheally. This was followed by a swift decrease of the number of sampled neutrophils. Seven days latter the neutrophil count returned to normal. A significant increase of alveolar macrophages was seen on the seventh day. The increased macrophage count correlated with the extent of the pulmonary emphysema destruction. PMID- 1493505 TI - [Free alveolar cells in experimental pulmonary emphysema. II. Morphological studies of cells and analysis of their adhesive properties]. AB - Morphological analysis of cells sampled by lavage from alveoli was carried out. Analysis of their adherent properties on a nylon filter was also studied. Morphological analysis was carried out by light and scanning electron microscopy (SEM). The authors have demonstrated a correlation between adherence of the cells to the filter and morphological characteristics of the cells. SEM disclosed a very rich configuration of the cytoplasmatic membrane and/or formation of philopodia and pseudopodia. These results correlated with the extent of emphysemic pulmonary changes. Light microscopy showed a thin veil formed by the cell membrane in cells showing highest adherent properties. PMID- 1493506 TI - [Does the moment of birth influence future atopic respiratory diseases? I. Statistical analysis]. AB - In order to define the possible role of the time of birth on future presentation of atopic respiratory disorders an analysis of birth rates was studied according to time of birth in the following groups: 111 patients with pollinosis 145 patients non-seasonal allergic respiratory disorders, 117 patients with non atopic respiratory disorders and 291 healthy volunteers Clinical diagnosis of atopic respiratory disease was based on the presence of conjunctivitis and/or mucosal inflammation and/or bronchial asthma. Confirmation of atopic etiology of the disorders was based on results of skin prick tests with common allergens and/or of allergen specific IgE levels. It was demonstrated that patients with respiratory disorders are born most often in the second quarter of the year. Patients with non-seasonal allergic disorders were born usually in the second and third quarter of the year. Patients that were born in the first quarter of the year developed atopic disorders less frequently. PMID- 1493507 TI - [Spirographic predicted values for young men in Poland]. AB - Basing on results of VC and FEV1 measurements in 293 males of the age group 15-40 years using the regression calculations new predictive values were calculated. These values were compared with values published 27 years earlier by Nikodemowicz and Morris's normograms. The latter published the highest reference values, on which most computer programs are based on. The analysis demonstrated significantly higher predictive values compared to those of Nikodemowicz, and comparable with the Morris's normograms. It seems that the latter can be used for reference values in Poland. PMID- 1493508 TI - [Coexistence of asthma and certain symptoms of atopic dermatitis]. AB - The frequency of basic and minor features of atopic dermatitis were compared between 86 patients with coexistent asthma, and 269 without asthma. The coexistence of asthma caused a statistically significantly more frequent presence of one of the basic features: personal or family history of atopy and five minor features. The latter included: early age of onset, recurrent conjunctivitis, tendency toward cutaneous infections, elevated serum IgE and keratosis pilaris. PMID- 1493509 TI - [The role of radiophotography in tuberculosis control programs in Poland]. AB - The role of mass radiophotography in Poland in the years 1985-1898 is presented basing on routine data from Antituberculous Centers and Radiophotographic Units. Mass radiophotography detects approximately 30% of new registered pulmonary tuberculosis cases. In the analysed period the number of radiophotographic examinations systematically fell. Also the percentage of the population that was screened using this method decreased, as well as, although to a lesser state, the percentage of new detected cases of pulmonary tuberculosis. A significant decrease in usage of mass radiophotography equipment was also seen. The economical cost of such examination increased. The role and place of mass radiophotography in tuberculosis control programs in Poland is discussed by the authors. It seems that first contact physicians will have the most pronounced role in early diagnosis of pulmonary tuberculosis. Also more emphasis should be placed on bacteriological diagnosis of tuberculosis. PMID- 1493510 TI - [The problem of diagnosing bronchial asthma in epidemiologic studies]. PMID- 1493511 TI - [Foreign bodies in the bronchial tree]. AB - In the study tree cases of foreign bodies in bronchial tree were discussed to illustrate a proper way for their removal. According to time of their remaining in bronchial tree a foreign body may be removed immediately after aspiration or after special preparation with surgical and anesthetic assistance. Our studies documented the use of flexible fiberoptic bronchoscope in foreign body removal. PMID- 1493512 TI - [Asthma and pregnancy]. PMID- 1493513 TI - [Cellular analysis of bronchoalveolar lavage fluid (BAL) in patients with acute and chronic bronchitis (preliminary study)]. AB - Cell morphology of BAL- fluid and index bronchitis (by Thompson) were evaluated in 52 patients with acute and chronic bronchitis. A significant increase of index bronchitis and percentage of neutrophils in BAL were observed in acute and chronic bronchitis. There was no correlation between index bronchitis and cell in BAL- fluid. PMID- 1493514 TI - [Interferon as a bronchospastic factor in patients with bronchial asthma]. AB - Twenty three asthmatics were examined during the symptoms free period. Each subject inhaled aerolised human interferon alpha (Hu IFN-alpha, Le) in increasing doses 4000 and 8000 units. IFN inhalation provoked significant decline in FEV1 (by 9.9% after the 1st dose and 6.6% after the 2nd dose on average). This results indicate that inhaled interferon induces bronchospastic reactions in asthmatics. PMID- 1493515 TI - [Activity of glucose-6-phosphate dehydrogenase in erythrocytes in patients with atopic asthma and allergic rhinitis]. AB - A significant decrease of erythrocyte G-6-P dehydrogenase activity in patients with atopic asthma and allergic rhinitis was observed. In order to define the cause of this phenomenon the enzyme was isolated from the cells. The kinetic and molecular properties of the erythrocyte G-6-P dehydrogenase were studied. A change in the Michaelis constant for G-6-P dehydrogenase was seen in erythrocytes of both patient groups. The thermoresistance at 45 C was reduced significantly. These modified properties can imply a change in the dehydrogenase molecule, this is seen more significantly in the group with allergic rhinitis. PMID- 1493516 TI - [Studies on the possibility of desensitizing patients sensitive to plant pollens and house dust by an oral route]. AB - Oral hyposensitization was carried out in 26 patients with pollinosis and in 67 patients sensitive to house dust with all year symptoms of allergic disease of the skin, airways or conjunctivitis. The patients were hyposensitized with grass pollen extracts and house dust produced by Lab. Sevac. The pollen allergen was administered before the pollinating season, in increasing doses during 18 weeks. The following concentrations were used: 0.1 PNU, 1.0 PNU, 10 PNU, 100 PNU, and 1000 PNU. The house dust allergen was administered in the same manner, using the same concentrations and time during autumn and winter. In the group of patients with plant pollinosis 10 out of 26 did not experience any symptoms of the disease after hyposensitization. In 9 further patients the symptoms were milder. In the group of 44 patients with atopic dermatitis sensitive to house dust, a complete cure was seen in 62% of the patients. In further 25% milder symptoms were observed. In the group of 11 patients allergic to house dust and with the asthma prurigo syndrome, the respiratory and dermatologic symptoms resolved completely or diminished in 3 and 6 patients respectively. In the group of 7 patients with dermatitis and full year rhinitis, complete resolvement of symptoms was seen in 2 patients and diminished symptoms in 3 cases. In the group of 4 patients with conjunctivitis full resolvement of symptoms was observed in 3, while partial in 1. Only in 3 out of 93 treated subjects intolerance of this therapy was found.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1493517 TI - [Phenologic observations of the Rabka health resort in 1990]. AB - Important factors decisive of the health resort's climatic characteristics are the results of aero-phenologic studies. These results take in account the different pollinating seasons of various plants, grasses and weeds. Quantification and qualification of air pollination using the volume method with a Burkhard analytical device. Basing on results the authors have found increasing pollination string from March. At his time the main pollens come from birch, hazel, alder, weeping willow. The concentration of these pollens decrease in April, completely diminishing in May. Grass pollens increase in mid-May, peaking in June to early August. Pine pollens are found in May and June. A characteristic feature of the phenologic calendar is pollination of grass and pines in the same period (late May and June). The results of this are seen in children treated at the Mother and Child Institute Branch in Rabka, who demonstrate increased signs of pollinosis. The results of this study should modify treatment and change prophylaxis in children treated in Rabka. PMID- 1493518 TI - [Changes of alpha-amylase activity in serum and urine of patients with various histological types of lung cancer]. AB - Serum and urinary activity of alpha-amylase was assessed in different types and clinical stages of lung cancer. Significantly increased activity was seen in adenocarcinoma and in stage III of the disease. Following surgical removal of the tumor alpha-amylase decreased on the 7th day by 19% and on the 21st day by 26.8%. The activity of urinary alpha-amylase also decreased. The authors have determined the thermostable fraction of the alpha-amylase which may imply the source of the enzyme in the serum. PMID- 1493519 TI - [Foreign bodies in the bronchi of adult patients]. AB - 846 bronchoscopies were carried out in adults between 1.01.1988 and 31.01.1991. 11 of these were performed in order to remove endobronchial foreign bodies. In 5 cases the foreign bodies were located in the bronchi of the right lung. In 1 case the foreign body was localized in the left lung. All were removed bronchoscopically. The youngest patients had 54 years, the oldest 82. The author discussed the diagnosis and removal of endobronchial foreign bodies. No complications were observed. PMID- 1493520 TI - [Bronchiolitis obliterans with organizing pneumonia and bronchiolitis obliterans]. PMID- 1493521 TI - [Pulmonary lymphangiomyomatosis]. AB - A case of pulmonary lymphangiomyomatosis in a female during menopause is presented. Difficulties in correct histopathological assessment of lung biopsies were met. The diagnosis was made after diagnosis lymph seeping into the pleural cavity. The patient was initially treated with prednisolone, tamoxifen followed by methyl progesterone and after characterizing the patient's hormone profile with danazol. Lymph seeping to the right pleural cavity was treated with pleural drainage and diet limitations. Lymph exudate to the left pleural cavity was controlled with local cytotoxic therapy. After 7 years of therapy and 8 years since the initial symptoms the state of the patient has deteriorated although she can perform every day chores and does not require oxygen therapy. High resolution CT scan disclosed extensive pulmonary changes implying extensive progression of the disease. PMID- 1493522 TI - [Lactate acidosis in the course of status asthmaticus--case report]. AB - A case report of lactate acidosis in the course of status asthmaticus in a 34 year old female is presented. The lactate acidosis was due to increased anaerobic glycolysis in respiratory muscles caused by decreased oxygen recruitment and increased oxygen consumption by respiratory muscles. The authors discuss the clinical significance of lactate acidosis and proper treatment of status asthmaticus. PMID- 1493523 TI - [Allergic alveolitis]. PMID- 1493524 TI - [Perspectives of immunomodulation with peptides in treatment of atopic diseases]. PMID- 1493525 TI - [Treatment of choking and prolonged foreign body]. PMID- 1493526 TI - [Cellular bronchoalveolar lavage (BAL) components and pulmonary function in chronic extrinsic allergic alveolitis]. AB - Bronchoalveolar lavage (BAL) and pulmonary function tests were carried out in 22 patients with chronic, extrinsic allergic alveolitis. In all a marked decrease of diffusion capacity was observed. The mean DLCO values was 34% predicted value. In 94% of the patients compliance was lowered. More pronounced abnormalities of pulmonary function (decrease of TLC and DLCO) were found with low BAL lymphocyte counts and increased macrophages count. The duration of the disease correlated with the absolute lymphocyte BAL count (r = -0.43). The BAL differential can be an additional measure of severity, duration of the disease process in chronic, extrinsic allergic alveolitis. PMID- 1493527 TI - Treatment of portwine stains using the pulsed dye laser. AB - Five years of clinical experience of the treatment of portwine stains using the flashlamp-pumped dye laser is presented. The dye laser, when turned to a wavelength of 577 nanometres with a short pulsewidth of the order of 340 microseconds, may be used to target selectively the dilated vasculature constituting the lesion. Patients with ages ranging from 5-45 years were treated under general anaesthetic using a computer controlled scanning system developed by the authors. Several repeat treatments were found to be necessary. Results are presented ranging from total eradication of the lesion to marginal lightening only. No scarring of the treated sites was evident. PMID- 1493528 TI - Management of the soft tissues in open tibial fractures. AB - This paper reviews the treatment of 168 open tibial fractures referred to the Northern Ireland Plastic Surgery Service over a 15-year period. Flap reconstruction was carried out in 133 (79%) and split skin graft cover in 22 (13%). There were 18 amputations (11%). There was a high incidence of complications among early post-injury fasciocutaneous flaps and late free flaps. Twenty-five primary free flaps were transferred without complication. The current management of open tibial fractures in this Unit is described. PMID- 1493529 TI - Comparative analysis of tissue fluorescence as related to capillary perfusion in random pattern skin flaps. AB - In random pattern skin flaps of mice, tissue fluorescence measured by means of videodensitometry at 24 h after flap elevation significantly correlates with intravital microscopically measured functional vessel density and viability of skin tissue as assessed by transmission light and electron microscopy. The correlation was found reproducible in non-ischaemic flaps (r = 0.86) and flaps being rendered ischaemic for 6 h after elevation (r = 0.98), indicating that increased microvascular permeability as a result of ischaemia/reperfusion does neither affect tissue fluorescence nor the accuracy of the fluorescein dye test. In addition, tissue fluorescence at 24 h after flap elevation accurately predicts ultimate flap survival on the 7th postoperative day with a sensitivity of 0.89 and a specificity of 0.85. These results suggest that in non-ischaemic as well as in ischaemic random pattern skin flaps tissue fluorescence can be used for assessment of nutritive blood flow, viability of skin tissue and ultimate tissue survival in these flaps. PMID- 1493530 TI - Neurocutaneous island flaps in the hand: anatomical basis and preliminary results. AB - The neurocutaneous flap is an axial flap composed of one vein and one nerve, the arterial vascularisation of which is provided by the vascular plexus around and inside the nerve. The vascularisation of the radial and ulnar nerves on the dorsal aspect of the hand were studied in 20 fresh upper limbs. There is always a consistent arterial longitudinal plexus alongside the nerves, which links the cutaneous perforating arteries. On the basis of our anatomical findings, neurocutaneous island flaps with retrograde flow were raised on the hands of five patients and are reported on. PMID- 1493531 TI - Trimmed second toetip transfer for reconstruction of claw nail deformity of the fingers. AB - Claw nail deformities of the fingers have been repaired by many methods, but the results have been cosmetically unsatisfactory because of loss of the distal phalangeal bone and the short nail bed. We have employed a trimmed second toetip including the distal phalangeal bone and excluding the germinal matrix as a vascularised composite flap for two patients with claw nail deformity of the fingers. The advantages of this method are that the repaired nail regrows to normal size and has bilateral nail folds. We believe that, in comparison with other conventional local or island flaps, this composite flap is functionally and cosmetically ideal for the repair of claw nail deformities. PMID- 1493532 TI - Desmoplastic melanoma: a clinico-pathological review. AB - Desmoplastic Melanoma (DM) represents a rare histological variant of melanoma. It has been described in isolated case reports as a cutaneous tumour with a high incidence of local recurrence and nodal metastases, requiring early aggressive surgery. However, overall clinical experience of the tumour is limited. 13 patients with DMM seen over a 20 year period were reviewed. The mean age at presentation was 67 years (range 34-87), and 2/3 of the lesions were in the head and neck. Tumour thickness averaged 5.78 mm (Breslow). 7 patients developed recurrence, 4 as regional nodes, and 3 as skin nodules. Four of these patients developed disseminated disease, of whom 3 died. The mean time to first recurrence was 26 months and mean follow-up time in the review was 40 months (range 3-141 months). PMID- 1493533 TI - Hydration and occlusion treatment for hypertrophic scars and keloids. AB - In 31 patients with hypertrophic scars or keloids, a side by side test was carried out to check the efficacy of an occlusive dressing technique using cream which did not contain silicone oil, versus a simple application of vaseline, used as a control. In all cases, the cream treated areas of scar and keloid demonstrated a remarkable improvement over that of the vaseline treated area. These findings strongly suggest that the mechanisms of hydration and occlusion are the main basis of the therapeutic action of this method in treating hypertrophic scars and keloids. PMID- 1493534 TI - Simple line closure for macrostomia repair. AB - In repair of macrostomia, many authors have used a Z-plasty to prevent postoperative scar contracture. We found that the Z-plasty scar may be conspicuous when the patients open their mouths. Here we present a method of nearly straight line closure resulting in an inconspicuous scar even when the patients move their mouths. PMID- 1493535 TI - Warfarin-induced complete bilateral breast necrosis. AB - Plastic surgeons are routinely consulted about the care of extended cutaneous necrosis. We present an unusual case of complete bilateral breast necrosis and review of the literature of warfarin-induced necrosis to inform plastic surgeons of new advances in the physiopathology of this entity. Warfarin-induced necrosis seems to be produced by an imbalance between circulating clotting factors and blood anticoagulation factors. PMID- 1493536 TI - Reconstruction of adactyly for 4th and 5th toes: the study of foot pressure. AB - Analysis of foot pressures in cases of reconstructed adactyly of the lateral toes is presented. Two cases with adactyly of the 4th and 5th toes in which new toes were created by cross-knee tubed pedicle flap were chosen and foot pressures of both the operated foot and the contralateral normal foot were measured postoperatively. The results did not indicate any functional disturbance after this method of reconstruction. PMID- 1493537 TI - Tetanus following human bite. AB - We present an unusual case of tetanus which followed a human bite. The patient, a 43-year-old woman, developed tetanus within 4 days of sustaining a human bite. She died 6 days after admission despite aggressive management in the intensive care unit. PMID- 1493538 TI - The syringe plunger in intraoperative hand surgery radiography. PMID- 1493539 TI - Staged distant muscle flap transfer using a forearm carrier. PMID- 1493540 TI - Cancrum oris reconstruction. PMID- 1493541 TI - Different ability in PC12 clones to recover from MMC toxicity following NGF treatment. AB - PC12 cells were cloned, and from their ability to form neurite-like processes 3 clones were selected: NGF-highly sensitive clone (HS), -moderately sensitive clone (MS), and -insensitive clone (IS). These clones were tested for the presence of specific NGF receptors by measuring the binding of 125I-labeled NGF. All 3 clones were capable of binding NGF, but the HS clone had more NGF receptors than the MS and IS clones. The effects of methyl mercuric chloride (MMC) and/or nerve growth factor (NGF) on these clones were tested. The HS clone was a little more susceptible to MMC than the MS and IS clones. When NGF was added to the culture medium in addition to MMC, cell recovery was observed. The tendency toward recovery was more prominent in the HS clone than in the IS one. Recovery in the MS clone was intermediate. These results suggest that NGF treatment can contribute to functional recovery of PC12 cloned cells from the cytotoxic effects of MMC depending on their ability to react to NGF. PMID- 1493542 TI - Influence of trigeminal nasal afferents on bulbar respiratory neuronal activity. AB - This study examined the influence of nasal trigeminal afferents, the anterior ethmoidal nerve (AEN) and posterior nasal nerves (PNN) on the spike discharges of respiratory-related neurons recorded in the ventral respiratory group (VRG) (2.6 3.5 mm lateral to the midline, from 1 mm rostral to 3 mm caudal to the obex and at depth of 2-4 mm below the dorsal surface). Electrical stimulations to the AEN and PNN were administered to 10 pentobarbital anaesthetized cats and to 8 ketamine anaesthetized, vagotomized, curarized and ventilated cats. Single shock stimulations of either nerve evoked transient and total inhibition of inspiratory activities. Expiratory-related neurons of the VRG presented three patterns of activity in response to stimulation:excitation, inhibition or inhibition followed by excitation. More generally, expiratory units are activated with a short latency. In the course of repetitive stimulation of the AEN and PNN we observed a prolongation of the spontaneous inspiratory discharge which presented transient, short inhibition in response to each shock. Most expiratory units presented a short activation which was synchronous with the transient inhibition of inspiratory activities. When repetitive stimulation provoked a sneeze-like response, we observed a progressive increase in the duration of transient inspiratory inhibition first, associated with a progressive reinforcement of transient expiratory activation. Secondarily, just before the expiratory thrust, we noted a stronger inhibition of the inspiratory activity which preceded a high frequency (400 Hz) expiratory discharge. Nasal afferents exert a forceful excitatory effect on bulbospinal (BS) and non-bulbospinal-non-vagal (NBS-NV) expiratory cells of the VRG. The effects due to vagotomy and curarization are discussed. PMID- 1493543 TI - Thymopoietin, a thymic polypeptide, prevents nicotinic agonist-induced morphological changes in neonatal muscle cells in culture. AB - Thymopoietin, a polypeptide hormone isolated from thymus and involved in immune function, potently inhibited [125I]alpha-bungarotoxin binding to neonatal muscle cells in culture (IC50 = 3.8 nM) and blocked carbachol-stimulated 22Na uptake with an IC50 of 1.9 +/- 0.2 nM and 23 +/- 7 nM at a half-maximal and maximal concentration of carbachol, respectively. Studies were subsequently done to evaluate potential long-term functional consequences of this interaction of thymopoietin at the nicotinic receptor. Exposure (1-3 days) of neonatal muscle cells in culture to nicotine (3 x 10(-6) M) or carbachol (1 x 10(-6) M) resulted in a decline in myotube branching and a decrease in myotube length. Thymopoietin did not appreciably alter myotube morphology on its own; however, it prevented the effects of nicotine and carbachol on muscle cell morphology at concentrations (1-10 nM) which corresponded well to those with which thymopoietin interacted at the receptor. The action of alpha-bungarotoxin on the myotubes was very similar to that of thymopoietin. These studies suggest that the endogenously occurring polypeptide, thymopoietin, has the potential to modulate muscle cell morphology through an interaction at the nicotinic receptor. PMID- 1493544 TI - Mechanically evoked perioral reflexes in infants. AB - Mechanically evoked activity in the superior and inferior segments of the orbicularis oris muscle was sampled in several young infants using a specially designed position-servo linear motor and a pacifier instrumented with eight miniature EMG electrodes. Unilateral stimulation of lip vermilion resulted in short latency, bilateral activation of the upper and lower lip recording sites. The ontogenesis of facial reflex sensitivity to mechanical inputs is discussed in relation to the acquisition of motor skills, including speech and smiling. PMID- 1493545 TI - Cell swelling induced by medium hyposmolarity or isosmolar urea stimulates gonadotropin-releasing hormone secretion from perifused rat median eminence. AB - Medium hyposmolarity between 10 and 50% and isotonic urea between 22.5 and 90 mM induced a dose-dependent burst of gonadotropin-releasing hormone (GnRH) secretion from perifused median eminence tissue which was maximal at 2-3 min and returned to near baseline by 5 min in spite of continued exposure to the stimulus. If Ca(2+)-free medium was used, osmotic stimulation of secretion was increased or unchanged, but secretion induced by 30 mM K+ was markedly reduced. Our data indicate that cell swelling induced by medium hyposmolarity or permeant molecules stimulates GnRH secretion from median eminence cells or cell processes as it does secretion from normal endocrine cells containing hormone stored in intracellular vesicles. In both, Ca2+ influx is not required or has a negative modulating influence on cell swelling-induced secretion. PMID- 1493546 TI - Cortical norepinephrine release elicited in situ by N-methyl-D-aspartate (NMDA) receptor stimulation: a microdialysis study. AB - Norepinephrine (NE) release measured by microdialysis from probes positioned in the prefrontal cortex of anesthetized rats was increased when N-methyl-D aspartate (NMDA) was contained in the microdialysis medium. NE release increased by a factor of 3.6 compared to prior baseline levels when 1 mM NMDA was applied for 30 min. This increase was largely reversible, and when a second stimulation was applied using aconitine (0.3 mM, 30 min), which acts on voltage-sensitive sodium channels, a second evoked release of NE was observed, of a similar magnitude as that evoked by NMDA. Dizocilpine (300 nM), which blocks cation channels associated with NMDA receptors, prevented the NMDA-elicited NE increase but not the aconitine-elicited increase. PMID- 1493547 TI - Somatic afferent fibers which continuously discharge after being isolated from their receptors. AB - A previous study in our laboratory has shown that some afferent axons produce prolonged discharges after the axons have been completely isolated. We have attempted to identify the type of afferent fibers displaying such activity. Single unit activity was recorded from a filament dissected from the distal stump of the cut sural or plantar nerve of an anesthetized rat. After thorough identification of the receptor type, the nerve was cut at a site between the recording electrode and the receptive field, completely isolating the fiber being recorded. Unit activity was recorded up to 1 h after sectioning the nerve. Upon sectioning the nerve, most units showed brief injury discharges lasting only a few seconds. However, 21 of 70 units exhibited prolonged discharges lasting at least 30 min after having been isolated from their receptors. These 21 units included 8 slowly adapting type II cutaneous mechanoreceptors, 3 Pacinian corpuscles and 10 muscle spindle afferent units. These results suggest that prolonged injury discharges can be produced in the axons of the slowly adapting type II cutaneous mechanoreceptors, Pacinian corpuscles, and muscle spindle afferents. This phenomenon may have important clinical and experimental consequences. PMID- 1493548 TI - Human fetal myelinated organotypic cultures. AB - We have previously reported the establishment of organotypic cultures derived from human fetal brain tissue. Although these cultures permit the testing of multiple hypotheses about normal human neurodevelopment and neuropathologic conditions, they have the limitation of not being myelinated and therefore preclude the study of questions related to myelinogenesis and diseases of myelin. In the current communication, we describe recent developments that allow us to overcome this limitation and permit the establishment of a myelinated organotypic culture model. Sections of dorsal column dissected from the lumbar spinal cord of human fetuses ranging in age 21-23 weeks of gestation were placed in culture. The explants were maintained for up to 12 weeks during which time they were characterized and shown to express a number of CNS cell-type-specific markers including glial fibrillary acidic protein (astrocytes), nerve growth factor receptor and neurofilament protein (neurons), CD68 (microglia), and myelin basic protein, HNK-1 and galactocerebroside (oligodendrocytes). In addition, lectin histochemistry using Ricinus communis agglutinin-1 detected microglia and endothelial cells. Upon explantation, abundant myelin was seen by electron microscopy in the cultures. Although during the culture period there was degradation of myelin, there was also evidence of maintenance of intact myelin sheaths around small caliber axons and de novo myelin synthesis. This model system may permit the further use of human organotypic cultures to investigate issues related to neurodevelopment and to pathologic conditions including those relevant to dysmyelination and demyelination. PMID- 1493549 TI - Action of picolinic acid and structurally related pyridine carboxylic acids on quinolinic acid-induced cortical cholinergic damage. AB - Picolinic acid, a pyridine monocarboxylic acid derived from tryptophan metabolism by the kynurenine pathway, was shown to block cortical cholinergic neurotoxicity induced by quinolinic acid (QUIN), a pyridine dicarboxylic acid yielded by the same pathway. This study examined the specificity of the anti-toxic effect of picolinic acid by comparing its effect with several structurally related mono- and dicarboxylic acids, and by evaluating its potential to influence cholinergic neurotoxicity produced by kainic, ibotenic and quisqualic acid. Picolinic acid or related agents were injected alone or in combination with a fixed dose of QUIN into the right nucleus basalis magnocellularis (nbM) of rats anesthetized with halothane. Cholinergic neurotoxicity was assessed 7 days post injection by measuring choline acetyltransferase (ChAT) activity in the frontoparietal cortex on the injected and uninjected side. In picolinate experiments, the staining of nbM neurons by acetylcholinesterase (AChE) histochemistry was also examined. Focal injections of QUIN depleted cortical ChAT activity and staining of AChE in the nbM. Co-injection of picolinic acid with QUIN attenuated the decline in these two cholinergic neuron markers. Isonicotinate (4-pyridine monocarboxylate), but not nicotinate (3-pyridine monocarboxylate), significantly attenuated QUIN's effect on cortical ChAT activity. Among several dicarboxylic acids examined, only dipicolinate (2,6-pyridine dicarboxylate) showed activity. It produced a modest QUIN-like effect, but in co-injection experiments it attenuated the QUIN-induced decrease in cortical ChAT. When co-injected into the nbM with a neurotoxic dose of kainic, ibotenic or quisqualic acid which produced a neurotoxic response comparable to that of QUIN, picolinic acid attenuated kainic acid-induced neurotoxicity, but not ibotenate or quisqualate neurotoxicity.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1493550 TI - Potential use of DPCPX as probe for in vivo localization of brain A1 adenosine receptors. AB - The suitability of (3H)DPCPX (8-cyclopentyl-1,3-dipropylxanthine), a xanthine derivative, as an vivo probe for labelling adenosine A1 receptors was studied in rats. [3H]DPCPX (nM) penetrated largely into the brain (0.8% of the injected dose per gram of brain tissue 5 min after injection). Brain concentrations stayed at a plateau level from 5 to 15 min after the injection. The distribution in the different brain regions was heterogeneous with the highest amount of [3H]DPCPX in cerebellum and hippocampus and the lowest concentrations in hypothalamus and brain stem. Displacement (45-70% of total radioactivity) was obtained by the injection of 250 nM of cold DPCPX or cyclopentylxanthine, an analog of DPCPX. The ex vivo autoradiographic distribution of [3H]DPCPX was similar to the in vitro autoradiographic distribution of tritiated A1 adenosine receptor ligand as [3H]CHA. These results suggest the potential use of DPCPX for further in vivo investigation of A1 adenosine receptors with techniques such as positron emission tomography. PMID- 1493551 TI - Cell surface extensions associated with overexpression of Alzheimer beta/A4 amyloid. AB - Deposition of beta/A4 amyloid in Alzheimer disease (AD) brain parenchyma and vasculature occurs by mechanisms that are currently undefined. Similarly the potential consequences of amyloid accumulation for disrupting cellular integrity have not been addressed in detail. To investigate the possible significance of amyloid deposits for cellular viability, PC12 cells were permanently transfected with DNA coding for the beta/A4-C terminal region of the amyloid precursor protein. The DNA represented 97 amino acids of the amyloid precursor protein of which 40 amino acids were derived from the beta/A4 region. Transfected clonal cell lines and controls were examined at both the light and electron microscopic levels for morphological abnormalities. beta/A4 amyloid accumulated in the cell membrane where the peptide was located at cellular processes resembling blebs and microvilli. These specialized structures at the cell surface were over-abundant in transfected cells that overexpressed the beta/A4 peptide but not in controls. Membranous processes may be involved in the delivery of the beta/A4 peptide to the external surface of the cell of origin and release into the extracellular space. Similar surface features of cells in the AD brain, should they occur, may indicate a role for membrane-associated processes in the pathophysiology of the disorder. PMID- 1493552 TI - Serotonergic reinnervation of the hamster suprachiasmatic nucleus and intergeniculate leaflet without functional circadian rhythm recovery. AB - Intraventricular injections of the neurotoxin, 5,7-dihydroxytryptamine (DHT), were used to lesion hamster forebrain serotonin systems. The entrained circadian wheelrunning rhythm was studied for up to 20 weeks post-lesion as was the extent of reinnervation of nuclei regulating circadian rhythmicity. Reinnervation of the suprachiasmatic nucleus and intergeniculate leaflet by serotonergic fibers begins by 8 weeks and progresses to substantial, but not complete, levels by week 20. Four measures of the nocturnal activity phase of the circadian rhythm were rapidly modified by the lesions, but in contrast to the morphology, persisted unchanged during the entire 20 week test period. The circadian rhythm system of hamsters may be fundamentally different from other behavioral or neuroendocrine systems studied in rats with respect to its inability to recover from damage to its serotonergic innervation. Alternatively, the failure to demonstrate functional recovery may reflect a species difference or insufficient recovery time. PMID- 1493553 TI - Effects of different rates of drying cassava root on its toxicity to broiler chicks. AB - 1. The effects of drying cassava root at different rates on its composition and toxicity to broiler chicks were examined. Unpeeled roots from a high-cyanide cultivar of cassava were chipped and dried at 25 degrees C to a moisture content of below 100 g/kg over 24 h for fast-dried meal (FD) or 72 h for slow-dried meal (SD). The meals were incorporated at 250 and 500 g/kg into semi-synthetic diets which were fed to day-old broiler chicks as mash or pellets in separate experiments. 2. The two drying rates produced meals with similar concentrations of polyphenols, but different concentrations of cyanogens, the latter being 38 and 482 mg total cyanide/kg for SD and FD, respectively. The linamarin, acetonecyanohydrin or total cyanide content measurements of pelleted diets were highly correlated. 3. Growth rates of chicks fed on SD-based diets were significantly higher than those of chicks fed on FD-based diets. Compared with a control diet, weight gain of chicks fed on the 500 g FD/kg diet (containing 258 mg total cyanide/kg) was 77% lower, although performance also appeared to be reduced at 142 mg total cyanide/kg. 4. The ratio of water:food intake of chicks was higher in FD than in SD groups, and this was reflected in the high water content of excreta. There was increased bile excretion, the chloretic effect increasing with the cyanogen content of diet. Pancreas weights were lower in FD than in SD groups in experiment 1 (mash diets), but not in experiment 2 (pelleted diets), while there was a significant interaction between drying method and cassava inclusion rate on liver weight in experiment 2, but not in experiment 1. There were no effects on the mortality rate. 5. Pelleting of diets generated high temperatures, but did not significantly alter the cyanogen concentration or the growth of the chicks. 6. Thus, slower rates of drying cassava roots produce meals with lower cyanogen concentration that are, consequently, less toxic to broiler chicks. Cassava root meal of less than 40 mg total cyanide/kg can be fed to broiler chicks at 500 g/kg without any adverse effects. PMID- 1493554 TI - Plasma oestrogen and triglyceride concentrations and reproductive characteristics of broiler chickens after ten generations of selection at seven weeks of age for high or low plasma very low density lipoprotein concentration. AB - 1. Day old female chicks from two lines of broilers, selected for high or low plasma concentrations of very low density lipoproteins, were fed ad libitum or restricted until point of lay. All birds were fed ad libitum after laying an egg, and aspects of growth and reproduction were measured to 40 weeks of age. 2. Compared with lean line birds the growth rate of fat line females fed ad libitum declined from 16 weeks of age. 3. Mortality from apparently stress-related causes in ad libitum fed fat line females increased from 16 weeks of age and was 71% overall, compared with 26% in ad libitum fed lean line females. Mortality in the corresponding restricted birds was 20% and 7%, respectively. 4. Few fat line females fed ad libitum commenced lay and those which were restricted during rearing stopped laying after the initiation of ad libitum feeding. Egg productions in lean line birds fed ad libitum or restricted were similar. 5. Fat line females fed ad libitum had few yellow follicles and a high rate of atresia at first egg and between 37 and 39 weeks, as did restricted fat line birds between 37 and 39 weeks of age after being fed ad libitum. 6. Plasma concentrations of oestradiol-17 beta were 5-fold higher in fat compared with lean line females at 35 weeks of age. There was a similar large difference in concentrations of plasma triglyceride which reached 59 mg/ml in fat line females fed ad libitum. PMID- 1493555 TI - Biological chick procedure to determine fluoride availability in sepiolite. AB - 1. A modified fluoride (F) bioassay procedure based on the method of standard additions and using chicks was tested for the determination of F availability in sepiolite. Chicks were distributed between a control group fed on a basal diet and experimental groups fed on this diet supplemented with 100, 200 or 300 mg/kg F as sodium fluoride. A further group was fed on the basal diet plus 2 g/kg sepiolite. 2. Body weight gain and food consumption during a 60 or 90 d study were similar for all treatments. 3. Ileal digestibility of F from the basal diet or from the diet supplemented with 200 mg/kg F as sodium fluoride was higher (0.907) than for chicks fed on the sepiolite diet (0.152). 4. Increases in the F contents of tibia ash were linearly related to dietary F concentration as sodium fluoride. 5. F contents of tibiae from the sepiolite group (at 60 or 90 d of age) were plotted against tibia F concentrations from groups receiving additional sodium fluoride in the diet. A weighted regression was performed. The values obtained for the relative available F from sepiolite were 0.213 and 0.150, respectively, at 60 and 90 d of age. PMID- 1493556 TI - Occurrence of intraportally-infused urea-15N in the urine of domestic fowl. AB - 1. Measurements were made in situ to determine the occurrence of intraportally infused urea-15N in ureteral urine of the fowl. 2. Of the total amount of infused urea-15N, 15% was excreted intact into the urine (90% of urinary total 15N) whereas 9% remained unchanged in the blood (78% of blood non-protein-15N). 3. The proportions of non-protein-15N in the blood, liver and kidney were 12, 3 and 1%, respectively of the infused 15N. Protein-15N was 3% of that infused in blood and much less in liver and kidney. 4. About 1% of the infused 15N was observed in the urinary uric acid, and 3% of the infused 15N in non-protein N, other than urea, ammonia and glutamine amide N, of blood and liver. 5. No appreciable amounts of 15N were present in ammonia and glutamine amide N of blood, liver or kidney and in uric acid of liver or kidney. 6. The caecal contents contained about 1% of the infused 15N with 15% of this as ammonia-15N. 7. It is concluded that intraportal urea is mostly excreted unchanged into ureteral urine of the fowl. PMID- 1493557 TI - Effect of dietary protein content on episodic growth hormone secretion and on heat production of male broiler chickens. AB - 1. The effect of the crude protein content (200 and 150 g/kg) of isoenergetic diets on episodic growth hormone (GH) release and on heat production was investigated in male broiler chickens. 2. Decreasing the crude protein content of isoenergetic diets from 200 g/kg (HP diet) to 150 g/kg (LP diet) resulted in depressed body weight gain, impaired food conversion efficiency and increased abdominal fat deposition. 3. The pattern of growth hormone secretion was markedly affected by dietary treatment. Broiler chickens fed on the LP diet had higher overall mean, amplitude, baseline and peak frequency than the HP chickens. 4. The LP chickens produced more heat per unit of metabolic body weight than the HP chickens. 5. The hypothesis relating the pattern of GH secretion to protein conversion efficiency was corroborated. PMID- 1493558 TI - Non-invasive determination of heart rate in newly hatched chicks. AB - 1. Using a flexible piezoelectric probe, we detected non-invasively the cardiogenic precordial movements of domestic fowl chicks and measured heart rate (HR) daily over the first week after hatching (day 0) for comparison with previously measured embryonic HR. 2. HR of the hatchlings was much more variable than embryonic HR. The mean HR at a given age also varied among the 5 chicks measured. 3. The overall mean HR was 280 +/- 20 (SD, n = 5) bpm on day 0. This value was similar to the prepipping HR and lower than that of externally pipped embryos. It increased to 342 +/- 39 bpm 3 days later. PMID- 1493559 TI - Composition, cortical structure and mechanical properties of chicken tibiotarsi: effect of growth rate. AB - 1. Comparisons of tibial growth in slowly (X) and rapidly (F) growing chicks were carried out weekly until the birds weighed 500 g. 2. Bone volume and percentage of ash per dry weight increased with age and were similar at equal body weights between crossbreeds. In birds of the same age, the ratio of tibial dry weight to hydrated weight was greater in crossbreed X as compared with crossbreed F. Consequently, the tibial density and the mineral content per volume were higher, at equal body weights, in crossbreed X. 3. Cortical cross-sectional area was greater in crossbreed F at the different ages, but was similar in both crossbreeds at equal body weights. A peripheral active zone of greater porosity was predominantly characterised by radial fibrolamellar tissue in fast growing birds and covered a larger area in crossbreed F than in crossbreed X. 4. Biomechanical properties of the tibiotarsi were evaluated in a three-point flexure test. The area moment of inertia was equal at similar body weights in both crossbreeds, but the yield or maximal forces and stiffness of tibiotarsi were lower in the rapidly growing crossbreed F compared with crossbreed X. 5. It is concluded that an increased rate of growth is associated with a lower mineral density and higher porosity of the tibial cortices resulting in reduced bending resistance. PMID- 1493560 TI - Variation in egg yolk cholesterol concentration between and within breeds of the domestic fowl. AB - 1. The pattern of variation for egg yolk cholesterol concentration between 5 commercial egg layer lines and a cross of Gallus domesticus is described. 2. Yolk cholesterol concentration in the cross was lower than in the lines, and 6.7% lower than the midparent value. 3. It is proposed that the reduced yolk cholesterol concentration of the cross may be a consequence of heterosis, although sex-linkage and/or maternal effects cannot be discounted. 4. The difference between the cross and parental lines is consistent with a physiological relationship between yolk cholesterol concentration and rate of egg production, but not between yolk cholesterol concentration and yolk weight. PMID- 1493561 TI - Determination of pyrimethamine and sulphadimethoxine residues in eggs by high performance liquid chromatography. AB - 1. Laying hens were given food containing per kg diet: 1 mg pyrimethamine, 10 mg sulphadimethoxine (SDM) or 1 mg pyrimethamine with 10 mg SDM, for 14 days. Residues in the eggs were determined by high performance liquid chromatography. 2. Pyrimethamine was mainly found in yolk. Its concentration was slightly higher when it was given with SDM. 3. The concentrations of SDM in eggs were not different when it was given alone or in combination with pyrimethamine. 4. After withdrawal, pyrimethamine residues decreased below the detection limit (0.02 mg/kg) in the yolk after 11 to 12 d and in the albumen after 2 to 3 d. SDM in yolk fell below the detection limit (0.01 mg/kg) on day 7, whereas in albumen it was not detectable after 2 to 3 d. PMID- 1493562 TI - [The contribution of overseas health and medical services in food and nutrition]. AB - This article reminds the contribution of Health and Medical Services in overseas territories and other developing countries. Seconded to Health Services, Pasteur Institutes, other scientific research Organisations, and International Organisations (FAO, WHO), medical doctors and pharmacists, properly trained in nutrition, have studied under-nutrition and malnutrition, and their effects on the health of the populations and the economy of their countries. Later, in cooperation with all departments concerned, they have realised a number of applied programmes, aiming at a real improvement in the situation or even the eradication of nutritional deficiencies. However the article deals mainly with actions related to food production and distribution, from the establishment of a national food policy to agriculture planning and evaluation, including specific, applied nutrition programmes in agriculture development and supplementary feeding programmes. PMID- 1493563 TI - [Commemoration of the hundredth anniversary of the death of Jean-Antoine Villemin (1827-1892)]. PMID- 1493564 TI - [Pharmacokinetics and therapeutic monitoring of cyclosporine in liver transplant recipients]. AB - Cyclosporine (CsA) has played a major role in the development of organ transplantation. However, its use in the prevention of liver graft rejection is somewhat delicate because the liver plays an essential role in the intestinal absorption, metabolism and excretion of CsA. Interindividual differences in CsA pharmacokinetics are large, and clearance can vary by a factor of 40 in liver transplant recipients. During CsA therapy, the intact molecule is assayed in whole blood by means of specific technique. The margin between immunosuppressive and nephrotoxic concentration is poorly defined. The interpretation of blood concentrations must take into account the mode of administration, associated drug therapy, the time since grafting, and pathological episodes. The recommend trough concentrations are 150-200 ng/ml during the first three months. PMID- 1493566 TI - [Request presented by Madame Guerin-Lemerdy with a view to obtaining authorization to manufacture allergens prepared specially for an individual in the locales of SARL "Allerbio"]. PMID- 1493565 TI - [Primary hyperparathyroidism. Results of a French multicenter study]. AB - The "Association francaise de Chirurgie" asked to authors an update on primary hyperparathyroidism based on a retrospective multicentric study on 4883 patients operated on by 79 surgeons. Aim of this study was an update on clinic and biologic aspects, localizing studies, and therapeutic aspects with their results. There were 3418 females (70%) and 1465 males (30%) mean age 53 years (9 to 91 years): 3702 solitary adenomas (75.8%), 720 multiglandular lesions (14.7%) 92 multiple endocrine neoplasias (1.9%) and 86 carcinomas (1.8%). None lesion was found in 283 cases (5.8%). To day, diagnosis is most often made on fortuitous hypercalcemia. Localising studies showed sensibility less than 50%. Surgery was successful in 92.7%. Mortality occurred in 0.6%, hypoparathyroidism in 3.8%, laryngeal palsy in 1.5% and hematomas in 0.45%. In conclusion this study shows the changes regarding the diagnosis, the uselessness of localizing studies before first cervicotomy, and the good results of surgery. Autotransplantation and cryopreservation allow reducing of hypoparathyroidism. PMID- 1493567 TI - [Eulogy of Marc Bolgert (1904-1991)]. PMID- 1493568 TI - [Deficiencies, disabilities and handicaps: taking responsibility for the young maladjusted child]. AB - A handicap should not be confused with deficiency or incapacity. It is the resulting difference between an individual's competencies and the situation which is proposed to, or imposed to, him. Whatever the type of deficiency a child may have, and the subsequent incapacity, it is important to discern for therapy, the positive aspects of his personality as soon as possible in order to develop his chances for success and avoid set backs. Structures such as the Medical and Social Early Action Center (CAMSP), which we created in 1976 at the Medical Center in Versailles, allow personalized care. More than progress in reference to an often illusory norm, it is the search for talents, aptitudes and, in function of this, the acquisition of knowledge, which should be the educator's concern. An excess of legislation may unfortunately lead to the standardization of the means and goals. PMID- 1493569 TI - [Three bacterial species associated with Lyme borreliosis. CLinical and diagnostic implications]. AB - DNAs from various Borrelia associated with Lyme disease were reciprocally hybridized. This genomic taxonomy method showed that Lyme disease agent comprised three genomic species. Two species could be differentiated by phenotypic characters as major proteins molecular weights and monoclonal antibodies reactivity. Western-blot with sera from patients suffering from different clinical forms of Lyme disease: arthritis, meningoradiculitis and Acrodermatitis Chronicum Atrophicans showed that each of these evolutive forms was preferentially associated with one of the species, respectively: Borrelia burgdorferi sensu stricto, Borrelia garinii and Borrelia group VS 461. Furthermore, geographical repartition of these three species was heterogeneous. B. burgdorferi sensu stricto seems to be the only one present in the United States of America, whereas it coexists in Europe mainly with B. garinii in Western Europe and Borrelia group VS 461 in Northern Europe. PMID- 1493570 TI - [Is thyroid cancer a severe cancer? (Prognostic study of 800 surgically-treated cases of which 143 nodular differentiated cancers were followed-up for more than 20 years)]. AB - The prognosis of thyroid carcinoma has always been difficult to appreciate because this rather rare carcinoma is polymorph and subject to some very late recurrencies. For these reasons an acceptable prognostic evaluation is only possible with an important material and very long follow-up. From 800 patients operated by the author, 102 (13%) had an extra-capsular tumor, which means for all authors a very poor prognosis. Still two groups must be separated: the anaplastic extracapsular tumors (33/102) gave a very low life expectancy with 17% survival at 5 years and no patient surviving at 8 years. In contrast the differentiated extracapsular tumors, mainly papillary, gave an unexpected survival rate of 35% at 15 years. The more frequent nodular form of differentiated carcinoma (698/800 = 87%) has a much better prognosis, but his slow evolution needs a long follow-up observation. From 160 patients operated on before 1971, 143 (90%) could be all followed during 20 years or more. The over all survival rate at the 20th year is 83% with 76% of patients free of any recurrence. The analysis of several factors showed that the extension of the primitive operation (lobectomy or total thyroidectomy) does not influence the long term results. More reliable prognostic factors are the degree of histologic differentiation of the tumor, and the age of the patient. Finally, in spite of an excellent overall long-term prognosis, three very late recurrencies were observed in the group of 143 patients followed more than 20 years, respectively 21, 22 and 31 years after the first operation. This makes impossible the certitude of definitive cure of any thyroid cancer. PMID- 1493571 TI - [Ethical and social problems posed by organ transplantation]. AB - Organ transplantation more than a scientific fact is now a social fact. Since the first organ transplantations in France, forty years ago, medicine demonstrated its ability to perform the operation and to obtain (what was more difficult) the tolerance of the graft but medicine so far remains unable to give the material: organs. These organs are given by the donor's relatives when the kidney is concerned and when it is a donation from a living person. But such donation remain strictly limited in our country (less then 5% of the kidney transplantations) due to the risk of moral pressure and commercialization. More often and for the other organs (liver, heart, lung) a the donation is obtained after death, a special and dramatic death: the brain death. The nowadays spectacular results of organ transplantation 70 to 80% survival rate at 10 years with a complete rehabilitation gave a considerable increase on the demand. Unfortunately organ transplantation is the victim of its success, the number of donor's organ being insufficient to satisfy the needs. So in December 1990, 6,055 patients were on the waiting list and only 3,772 (56%) were transplanted. In December 1991, 6,334 patients were on the waiting list and may be only 4,000 could be transplanted. So the difference between the needs and the possibilities is increasing each year with for consequences, the death of 10% of the waiting patients and, for those who could be transplanted, a considerable increase in the waiting period responsible for slow deterioration of their status and less chances of success. The reason of the lack of organs is not due to the lack of brain deaths which are unfortunately too numerous, but to the impossibilities of organ retrieval due to: too advanced age or the presence of a transmissible disease of the donor, lack of medical means in some intensive care units, and family refusal. This refusal is easily understood and due to the very peculiar conditions in which the donation is required: the unexpected death of a loved parent and such a death with some life appearance. To avoid the increasing number of such refusal two actions are possible. One is the modification of the law. The French law is the Caillavet law which requires for organ retrieval, the written permission of the parents for a minor, or for an adult the absence of refusal expressed during his or her life.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1493572 TI - Modelling of the qualitative discrimination of odours in the first two layers of olfactory system by Jutten and Herault algorithm. AB - The olfactory system discriminates many different odours although membrane receptors, and neuroreceptors that bear them, are only broadly tuned to volatile molecules. We investigated how mixed and redundant information carried by neuroreceptors could be efficiently coded by output neurons in the second neuronal layer in the brain. We showed that a good discrimination is yielded if neuroreceptors that terminate on the same output neuron belong to several types, if these types are in different proportions for each output neuron, and if each output neuron exerts an action on all others so that their independence is maximized, according to the Jutten and Herault algorithm for separating linear mixtures of independent sources. The proposed model details the computations made by neurons and leads to a better understanding of several observed properties of the olfactory system, among which the inhibitory actions of local neurons of the second layer and the identifiability of insect glomeruli. PMID- 1493573 TI - Peptide binding to MHC class I proteins measured with a novel fluorescent technique. AB - An N-dansylated peptide derived from the Plasmodium berghei circumsporozoite protein (PbCS 253-260) bound in an allele-specific manner to a single-chain Kd molecule (SC-Kd), and its binding resulted in significant fluorescent enhancement. The binding kinetics of unlabelled peptides could be determined by pre-incubating dansylated PbCS with a concentrated suspension of SC-Kd, and then diluting this mixture in the presence of unmodified peptide. The time-dependence of the ensuing fluorescence decrease could be fitted to a single-exponential, which gave an association rate constant of 77 M-1s-1 for unlabelled PbCS. PMID- 1493574 TI - [Changes in heart genome expression in hypertensive diseases]. AB - Chronic increases in haemodynamic load modify the expression of cardiac genes, leading to cardiac hypertrophy and a new phenotype. As an example, changes in the expression of the genes encoding the main contractile proteins, the isomyosin heavy chains, have been associated with modifications of the physiological properties of cardiac muscle. The cellular and molecular mechanisms which either do or do not initiate and maintain these changes in cardiac genomic expression remain to be elucidated. Using in situ hybridization we show that mRNAs encoding a cellular form of fibronectin (c-FN), a protein of the basal membrane which is not or poorly expressed in adult rat heart, are reexpressed as a result of severe hypertension with a similar time course than the beta-heavy chain of myosin (beta MHC), also mostly expressed in fetal heart. The accumulation of the c-FN mRNAs was found in the wall of coronary arteries whilst that of the beta-MHC mRNAs occurred in the myocytes at the border zone of these arteries. Thus a high pressure in the arteries could be the trigger inducing the synthesis of factors which could, through a gradient, modulate the phenotype of both the smooth muscle cells of the media and the cardiocytes. Besides, using a model of cultured adult rat cardiocytes, we show that the differential expression of the MHC isoforms is dependent on the beta-adrenergic stimulation but that the regulation depends on the stage of development of the cells and differs for the alpha and beta MHC. These 2 complementary approaches for identifying the molecular mechanisms that control cardiac muscle growth should help for understanding cardiac adaptation triggered by haemodynamic overload, such as arterial hypertension as well as cardiac failure. PMID- 1493575 TI - [Platelets and aging]. AB - Platelets seem involved in pathogenesis of atherosclerosis and Alzheimer disease which frequency increases with population ageing. Platelet hyperactivation may contribute to atherosclerosis by release of factors, which increase fibroblast and smooth muscle cell proliferation and perhaps lipid deposition. Many studies evidenced an increased platelet activation with ageing concomitantly to an increase of some coagulation factors, and an impaired response of endothelial cells leading to a prethrombotic state and facilitating the occurrence of atherosclerosis. On the other hand, in Alzheimer disease, a deposit of amyloid beta protein responsible for vascular and neuronal damage was evidenced. Platelet activation is responsible for the release of an amyloid beta protein precursor (the protease nexin 2). An increased platelet activation as demonstrated with aging, may thus explained the increased occurrence of Alzheimer disease. PMID- 1493576 TI - [Platelet plasma membrane: characterization of the serotonin transporter]. AB - After treatment of human platelets by a sulfhydryl-dependent bacterial protein cytolysin, a glycoprotein was reproducibly purified by a one-step affinity chromatography using 6-fluorotryptamine as ligand and elution by serotonin (5 HT), cyanoimipramine, citalopram, or a Na(+)-free buffer. The purified fraction migrated on sodium dodecyl sulfate-polyacrylamide gel electrophoresis as a single band with an apparent molecular mass of 68 kDa. The purified glycoprotein bound the 5-HT uptake blockers 3H-paroxetine, 3H-cyanoimipramine, and 3H-citalopram with Kds similar to the ones observed for intact human platelets. No binding was detected with 3H-hydroxytetrabenazine, 3H-ouabain, 3H-gamma aminobutyric acid or 3H-BTCP, the respective markers of the granular monoamine transporter, the plasma membrane Na+, K(+)-ATPase, the gamma aminobutyric acid and dopamine carriers. The purified 68-kDa glycoprotein is therefore likely to correspond at least to the paroxetine and imipramine binding domains of the 5-HT transporter located at the human platelet plasma membrane. Finally a 68-kDa protein was purified in the same conditions from the human megakaryocytic cell line Dami and to a lesser extent from the human megakaryoblastic cell line MEG-01 but not from the human erythroleukaemic cell line HEL. PMID- 1493577 TI - [Demonstration of a protector effect of interleukin-1 against hematologic toxicity of azidothymidine (AZT)]. AB - 3'-azido-3'-deoxythymidine (Azidothymidine or AZT) has attained wide critical utility in the treatment of acquired immunodeficiency syndrome (AIDS). Unfortunately, treatment with AZT is associated with the development of severe hematopoietic toxicity. The AZT sensitivity of marrow progenitors was different with an IC 50 of 10(-8) M and 10(-6) M for respectively BFU-E and CFU-GM/GEMM. Data reported here show that recombinant human interleukin-1 alpha (IL-1 alpha), a pleiotropic cytokine, was demonstrated to be efficient to protect normal human as well as murine hematopoietic progenitors (CFU-GM, CFU-GEMM and BFU-E) from the toxic effect of AZT. The maximal effect was observed with 30 U/ml (Human cells) or 100 U/ml (murine cells) IL-1 alpha for BFU-E and CFU-GM/GEMM, with a marked effect at 1 U/ml. The results demonstrate that marrow progenitors respond differently to AZT and point out the potential efficacy of IL-1 alpha to enhance the proliferation of hematopoietic stem cells treated with growth factors (IL-3, erythropoietin) and to minimize the hematopoietic toxicity associated with AZT treatment. PMID- 1493578 TI - [Participation of cytokines and immune sera to the cytoadherence of erythrocytes infected by Plasmodium falciparum on the endothelial cells in culture]. AB - In vitro binding capacity of erythrocytes infected with P. falciparum and the modulation of cytoadherence on human endothelial cells by cytokines and sera from semi immune subjects in relation to cytoadherence were studied. Tumor necrosis factor and interleukin-3, alone or in combination with granulocyte macrophage colony stimulating factor, enhanced in vitro cytoadherence. Contrary to pooled immune sera, patients' sera obtained during acute or convalescent phase did not reverse nor inhibit in vitro cytoadherence. PMID- 1493579 TI - [Study of possible influence of mixed lymphocyte reaction on experimental models used in biological dosimetry]. AB - The study aimed to investigate whether "mixed lymphocyte reactions" could interfere with the results of experiments in which irradiated blood from one person is mixed with non-irradiated blood from another. This experimental model had been designed to simulate, in vitro, non-homogeneous in vivo exposure such as could occur after accidents with ionizing radiation. The results show that the experimental models gives valid results for donors with related blood characteristics. PMID- 1493580 TI - [Free radicals, lipid peroxidation and muscular ischemia]. AB - The role of oxygen free radicals in ischemia and reperfusion injury of skeletal muscle has not been well defined, partly because of the relative resistance of this tissue to normothermic ischemia. Under normal conditions small quantities of oxygen free radicals are produced but they are quenched by intracellular free radical scavenging enzymes (superoxide dismutase, catalase and glutathione peroxidase) or alpha-tocopherol. The increase in malondialdehyde suggests increased lipid peroxidation initiated by free radical reactions. Lipid peroxidation is potentially a very damaging process to the organized structure and function of membranes. The results of recent studies indicate that: a) oxygen free-radicals mediates, at least in part, the increased microvascular permeability produced by reoxygenation, b) free radical scavengers can reduce skeletal muscle necrosis occurring after prolonged ischemia. Additional evidence support the hypothesis of the interrelationship between ischemic tissue and inflammatory cells. So capillary plugging by granulocytes and oxygen free radical formation may contribute to the ischemic injury. PMID- 1493581 TI - [Malondialdehyde production and erythrocyte membrane resistance to free radicals, in function of adequate or inadequate protein intake, associated with different oils (sunflower, soybean, coconut, salmon)]. AB - Requirements in polyunsaturated fatty acids (PUFA) of series n-3 and n-6 may be amplified and their metabolism, transport, and utilization may be impaired in the long term, by protein depletion. The aim of this study was to evaluate, in young rats, malondialdehyde (MDA) production and erythrocyte membrane antioxidative defense, when they were fed balanced (20% casein) or depleted (2% casein) protein diet associated with various oils (sunflower, soybean, coconut or salmon). Over a short period (28 days), eight groups of 10 male Wistar rats were fed eight different diets: TOC (20% casein + 5% sunflower oil), TOd (2% casein + 5% soybean oil), SOC (20% casein + 5% soybean oil), SOd (2% casein + 5% soybean oil), COC (20% casein + 5% coconut oil), COd (2% casein + 5% coconut oil), SAC (20% casein + 5% salmon oil), SAd (2% casein + 5% salmon oil). Blood was removed, MDA was assessed in plasma (reaction with thiobarbituric acid). Washed erythrocytes were subjected to organic free radical generator (Kit KGRL 400 Spiral R.D., Couternon, 21560 France). The haemoglobin released was analysed by spectrophotometry. The total anti-radical defense status was expressed as the length of time to reach 50% hemolysis (T 50% in min). Plasma of deficient groups (2% casein) exhibited low concentrations of protein, particularly with coconut and salmon oils; phospholipid and total cholesterol, excepted with diet containing coconut oil; triacylglycerol; and VLDL. Malondialdehyde. In groups fed balanced protein diets, the lowest values were obtained with salmon and coconut oils. MDA contents of groups TOd, COd and SAd were higher than those of their respective control groups, but significantly only in group COd. Antiradical defense status. Total anti-radical defence status in erythrocytes was not modified in the short term by balanced or depleted protein diets which ever oil was used, despite deep changes in fatty acid composition of membrane phospholipids. In particular, phospholipid contents in eicosapentaenoic, docosahexaenoic acids were greatly enhanced by the consumption of salmon oil compared to the values obtained with coconut oil. PMID- 1493582 TI - Application of alkaline unwinding assay for detection of mutagen-induced DNA strand breaks. AB - The frequency of single-strand breaks in parental DNA and gaps in nascent DNA in various cells exposed to methyl methanesulfonate (MMS) or methylnitrosourea (MNU) was investigated by alkaline unwinding assay using two types of alkaline lysis conditions, 22 degrees C lysis versus 0 degrees C lysis. The DNA damage induced by MMS and MNU is considered to be characteristic of lesions produced in DNA by alkylating agents. The aim of our research project was to adjust this method to be able to detect the greatest number of DNA lesions induced by alkylating agents in parental DNA of different mammalian cells. In our experiments we used human cell lines EUE, GM637 and XP12, Chinese hamster V79 cells, and Syrian hamster embryo cells. The higher level of strand interruptions was detected under conditions of lysis of cells at 22 degrees C. Probably the level of strand interruptions found after the lysis of cells at 22 degrees C correlates with the increased number of disrupted alkali-labile sites of DNA. It is remarkable that the different lysis conditions did not influence the number of gaps detected in nascent DNA of alkylated cells. Comparing induction of breaks and gaps in radiolabelled strands of parental and daughter DNA under different lysis conditions, we succeeded in defining the optimum conditions for detection of alkali-labile sites of parental DNA. PMID- 1493583 TI - An evaluation of three pesticides: piritione, supercypermethrin and metolachlor in transformation bioassays of BHK21 and hamster embryo cells. AB - In a study of potential carcinogenicity of pesticides, Piritione, metolachlor (in the form of Dual and VUCHT 524) and Supercypermethrin (in the form of Supercypermethrin EC and Supercypermethrin TP) were assayed for induction of anchorage independent growth of BHK21 cells and morphological transformation of Syrian hamster embryo cells. The activity of these substances in both transformation assays was compared to the activity of the direct-acting ultimate carcinogen N-methyl-N-nitrosourea. In comparison to the very strong transforming activity of N-methyl-N-nitrosourea all pesticides tested with or without S9 fraction manifested a very weak, weak, medium or strong effect. The ability to induce anchorage independent growth was graded as follows: Dual < Supercypermethrin EC < Supercypermethrin TP < or = Piritione < VUCHT 524. Results of Syrian hamster embryo cell transformation assay were very similar to the BKH21 transformation assay. VUCHT 524 strongly induced transformation whereas Dual was inactive. Piritione and Supecypermethrin EC and Supercypermethrin TP elicited a slight but significant positive response. PMID- 1493584 TI - Attempts to use the HPRT-assay as an automated short-term monitor for an acute exposure to mutagens. AB - Attempts have been made to use the hypoxanthine-guanine-phospho-ribosyl transferase-assay as a method for automated screening of agent-induced phenotypic variants of human peripheral lymphocytes reflecting 6-thioguanine resistance and assumed to indicate genotoxic action. Different protocols of the hypoxanthine guanine-phospho-ribosyl-transferase-system were used in this study in order to investigate whether the system can be a candidate for a short-term test for a rapid and reliable identification of biological systems exposed to agents. The current protocols were based on: 1) fluoresceinated monoclonal antibodies against bromodeoxyuridine-DNA for labelling of 6-thioguanine-resistant human lymphocytes and direct flow-cytometric enumeration of bromodeoxyuridine-positive events and: 2) indirect flow-cytometric enrichment of 6-thioguanine-resistant cells labelled with 3H-thymidine followed by autoradiographic enumeration of positive events. Both the direct and the indirect enumeration method yielded similar results down to the range 10(-4) with respect to frequency of variants. For the less time consuming direct enumeration method the resolution was limited due to non specific binding of the antibody and false positives. It was, nevertheless, sufficient to score variants induced in vitro with the mutagens EMS, MMC and TT in the same range as e.g. that of cancer patients during and after chemotherapy or radiotherapy, or that of psoriasis patients during the after PUVA (8 methoxypsoralen and long range UV light)-therapy. We conclude that the direct enumeration protocol can be used for a rapid screening of so called outliers, but a more sensitive test, such as the more time-consuming enrichment protocol based on autoradiography, must be used in order to score variants in the range 10(-5) 10(-6). PMID- 1493585 TI - The hen's fertile egg screening test (HEST): a comparison between the acute toxicity for chick embryos and rodents of 20 drugs. AB - The possibilities of using developing chick embryos for evaluating drug activities and toxicities were studied by determining LD50 values for 20 drugs with 14 different pharmacological activities. Fifteen-day old chick embryos received drugs through the air cell and deaths were measured at 48 hr after the treatments. The LD50 values were determined and compared to the i.v., i.p., s.c. and p.o. values from mice listed in the Registry of Toxic Effects of Chemical Substance. The systemic toxicity of 15-day-old chick embryos to drugs were similar to those of mice with the following exceptions. The chick embryos seemed to be more sensitive than mice to antineoplastic or antibiotic agents such as actinomycin D and doxorubicin, whereas, LD50 values of cholinergic and cholinergic blocking drugs by this method were 10 to 20 fold of LD50 (i.v.) of mice. These observations are important for applying the hen's fertile screening test (HEST) to the determination of drug activities other than that of embryo toxicity or teratogenic activity. PMID- 1493586 TI - Testosterone metabolism in an in vitro skin model. AB - The metabolic activity of skin is important in penetration of topically applied compounds. Currently, animal or cadaver skin is used to evaluate the relationship between metabolism and penetration. In the present study, testosterone metabolism and penetration in a three-dimensional human skin model consisting of keratinocytes and fibroblasts derived from neonatal foreskins was characterized. Pieces of the model were placed on tissue culture inserts with HEPES-buffered medium on the dermal side. Penetration of [3H]testosterone was faster at 32 degrees C than 4 degrees C suggesting that metabolism affected penetration. To evaluate this metabolism, [3H]testosterone was applied to the stratum corneum side of the skin model. Radiolabeled metabolites released into the medium after incubation were separated by HPTLC and analyzed by autoradiography. This skin model metabolized [3H]testosterone to both more polar and non-polar compounds which were similar to metabolites of neonatal foreskins. The appearance of non polar compounds was earlier than the appearance of polar compounds. Both dermal fibroblasts and differentiated epidermal keratinocytes contributed to the metabolism of testosterone. Two testosterone metabolites, dihydrotestosterone and androstane-3, 17 diol, were reduced by addition of the cytochrome P-450 inhibitor metyrapone and were only produced by the keratinocytes. In conclusion, this model is a reproducible source of metabolically active skin and therefore a good alternative to animal or cadaver skin for evaluation of the contribution of metabolism to penetration. PMID- 1493587 TI - Cadmium-2-acetylaminofluorene interaction in isolated rat hepatocytes. AB - Cadmium (Cd) is a non-essential, highly toxic heavy metal and a ubiquitous environmental contaminant. Evidence exists that Cd can affect parameters which are of great importance in the response towards xenobiotics. However, there is a lack of information about the mechanisms that take place at the cellular and molecular levels upon dual exposure to Cd and other toxins. The purpose of the present work was therefore to examine the biochemical interactions between Cd and a well-known genotoxic hepatocarcinogen, 2-acetylaminofluorene (AAF) in isolated rat hepatocytes. The cells were incubated for 10 hr with a sub-cytotoxic concentration (0.22 microM) of 109Cd. This was followed by a 10 hr exposure to 1 microM [3H]AAF. Cellular distribution of Cd and 3H was determined. Sephadex G-75 elution profiles of the cytosol showed that Cd was almost entirely associated with the intermediate molecular weight (IMW) fractions containing metallothionein (MT) ( > 80%), and with high molecular weight proteins. In parallel, the highest proportion of 3H was found in the low molecular weight components. Further analysis of IMW fractions by DEAE A-25 anion-exchange chromatography revealed that, in addition to Cd, there was some 3H which coeluted along with MT-I and MT II isoforms, but preferentially with MT-I. Moreover, Cd pretreatment caused a 1.6 fold increase in MT level, as measured by the silver-saturation assay. Under these conditions, there was a 17% lower binding of 3H to the DNA. This reduced binding was neither accompanied by diminished AAF uptake nor by inhibition of cytochrome P-450 activity. Taken together, these results suggest that Cd exposure has a protective effect against the genotoxicity of AAF. MT, whose synthesis is induced, could play a role in the Cd-AAF interaction through scavenging of reactive metabolites. PMID- 1493588 TI - Regulation of intestinal glucose transport. AB - The small intestine is capable of adapting nutrient transport in response to numerous stimuli. This review examines several possible mechanisms involved in intestinal adaptation. In some cases, the enhancement of transport is nonspecific, that is, the absorption of many nutrients is affected. Usually, increased transport capacity in these instances can be attributed to an increase in intestinal surface area. Alternatively, some conditions induce specific regulation at the level of the enterocyte that affects the transport of a particular nutrient. Since the absorption of glucose from the intestine is so well characterized, it serves as a useful model for this type of intestinal adaptation. Four potential sites for the specific regulation of glucose transport have been described, and each is implicated in different situations. First, mechanisms at the brush-border membrane of the enterocyte are believed to be involved in the upregulation of glucose transport that occurs in streptozotocin induced diabetes mellitus and alterations in dietary carbohydrate levels. Also, factors that increase the sodium gradient across the enterocyte may increase the rate of glucose transport. It has been suggested that an increase in activity of the basolaterally located Na(+)-K+ ATPase could be responsible for this phenomena. The rapid increase in glucose uptake seen in hyperglycemia seems to be mediated by an increase in both the number and activity of glucose carriers located at the basolateral membrane. More recently, it was demonstrated that mechanisms at the basolateral membrane also play a role in the chronic increase in glucose transport observed when dietary carbohydrate levels are increased. Finally, alterations in tight-junction permeability enhance glucose absorption from the small intestine.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1493589 TI - Evidence for endothelium-dependent and endothelium-independent vasodilation in human skin flaps. AB - Acetylcholine (ACh) and nitroglycerin (NTG) were used as probes to study endothelium-dependent and endothelium-independent vascular relaxation in isolated perfused transverse paraumbilical human skin flaps. It was observed that ACh (10( 6) M) significantly (p < 0.05) decreased the vascular resistance and increased dermal capillary perfusion (assessed by surface fluorometry) in norepinephrine (NE, 10(-6) M) preconstricted skin flaps, despite the presence of a cyclooxygenase inhibitor (indomethacin, 3 x 10(-5) M) and a beta-adrenergic receptor antagonist (propranolol, 10(-6) M). The ability of ACh to induce vascular relaxation in NE-preconstricted skin flaps was lost after damaging the vascular endothelial lining with saponin perfusion (100 mg.L-1, 5 min). In contrast, NTG (10(-6) M) induced vascular relaxation to a similar extent before and after saponin treatment. In a separate study, ACh was seen to induce vascular relaxation in a concentration-dependent manner in skin flaps preconstricted with NE (10(-6) M). This vascular relaxation effect of ACh over the dose range of 10( 9)-10(-5) M was significantly (p < 0.01) inhibited in the presence of N omega nitro-L-arginine (10(-5) M), a nitric oxide (NO) synthesis inhibitor. These observations were taken to indicate the presence of endothelium-dependent and endothelium-independent vascular relaxation in human skin flaps and that the ACh induced endothelium-dependent relaxation is probably mediated by NO. The importance of impairment of endothelium-dependent relaxation in the pathogenesis of skin flap ischemia, and the potential use of topical nitrovasodilators or NO donors for prevention and (or) treatment of skin flap ischemia were also discussed. PMID- 1493590 TI - Abnormal magnesium metabolism in two rat models of genetic hypertension. AB - Magnesium concentrations in erythrocyte ghosts and arterial tissue of male, spontaneously hypertensive rats (SHR) were significantly less than in these tissues of male normotensive controls (Wistar-Kyoto; WKY) of the same age, which were also fed rat chow and tap water. The magnesium concentration in SHR erythrocyte ghosts was increased to the control value by incubating SHR erythrocytes with WKY blood plasma; SHR plasma did not affect the magnesium concentration in WKY erythrocyte ghosts. The magnesium concentrations in erythrocyte ghosts, aortas, and mesenteric arteries from female salt-sensitive (SS/JR) and salt-resistant (SR/JR) Dahl-derived rats, both maintained ad libitum on laboratory rat chow and either tap water or 0.9% NaCl, were not different but were significantly less than those of Sprague-Dawley rats considered as controls. While the ingestion of 0.9% NaCl had no effect on the magnesium concentrations measured in these animals, it caused the salt-sensitive rats to become severely hypertensive. It is evident from these observations that the decreased binding of magnesium to the plasma membrane of cells may be an inheritable metabolic defect that may be associated with the development of hypertension. However, in those instances of hypertension in which this defect occurs, it appears to be a contributing cause of the hypertension; by itself the defect is not a cause of hypertension. PMID- 1493591 TI - Effects of K+ on the twitch and tetanic contraction in the sartorius muscle of the frog, Rana pipiens. Implication for fatigue in vivo. AB - The effects of increasing the extracellular K+ concentration on the capacity to generate action potentials and to contract were tested on unfatigued muscle fibers isolated from frog sartorius muscle. The goal of this study was to investigate further the role of K+ in muscle fatigue by testing whether an increased extracellular K+ concentration in unfatigued muscle fibers causes a decrease in force similar to the decrease observed during fatigue. Resting and action potentials were measured with conventional microelectrodes. Twitch and tetanic force was elicited by field stimulation. At pHo (extracellular pH) 7.8 and 3 mmol K+.L-1 (control), the mean resting potential was -86.6 +/- 1.7 mV (mean +/- SEM) and the mean overshoot of the action potential was 5.6 +/- 2.5 mV. An increased K+ concentration from 3 to 8.0 mmol.L-1 depolarized the sarcolemma to -72.2 +/- 1.4 mV, abolished the overshoot as the peak potential during an action potential was -12.0 +/- 3.9 mV, potentiated the twitch force by 48.0 +/- 5.7%, but did not affect the tetanic force (maximum force) and the ability to maintain a constant force during the plateau phase of a tetanus. An increase to 10 mmol K+.L-1 depolarized the sarcolemma to -70.1 +/- 1.7 mV and caused large decreases in twitch (31.6 +/- 26.1%) and tetanic (74.6 +/- 12.1%) force. Between 3 and 9 mmol K+.L-1, the effects of K+ at pHo 7.2 (a pHo mimicking the change in interstitial pH during fatigue) and 6.4 (a pHo known to inhibit force recovery following fatigue) on resting and action potentials as well as on the twitch and tetanic force were similar to those at pHo 7.8. Above 9 mmol K+.L-1 significant differences were found in the effect of K+ between pHo 7.8 and 7.2 or 6.4. In general, the decrease in peak action potential and twitch and tetanic force occurred at higher K+ concentrations as the pHo was more acidic. The results obtained in this study do not support the hypothesis that an accumulation of K+ at the surface of the sarcolemma is sufficiently large to suppress force development during fatigue. The possibility that the K+ concentration in the T tubules reaches the critical K+ concentration necessary to cause a failure of the excitation-contraction coupling mechanism is discussed. PMID- 1493592 TI - Brush border membrane proteins in experimental Fanconi's syndrome induced by 4 pentenoate and maleate. AB - Fanconi's syndrome was investigated using brush border membrane (BBM) vesicles isolated from dog kidney. Sodium-dependent uptake of glucose, phosphate, and amino acids and protein phosphorylation were studied in BBM isolated from normal and from 4-pentenoate- and maleate-treated animals. The time course of D-glucose and phosphate uptake, in BBM vesicles, remained unchanged, indicating that both treatments had no effect on carrier properties, and that permeabilities to these substrates and to sodium were not modified. Furthermore, sodium-dependent transport of alanine, phenylalanine, proline, glycine, and glutamate into vesicles remained unaltered by either treatment. 4-Pentenoate treatment caused modifications of the phosphorylation pattern of BBM proteins: the phosphorylation of two proteins (61 and 74 kDa) was increased and that of two others (48 and 53 kDa) was decreased. Maleate treatment caused an increase in the phosphorylation for the same 61-kDa protein, which was also affected by 4-pentenoate treatment, suggesting that phosphorylation of this protein could be related to a mechanism involved in both 4-pentenoate- and maleate-induced Fanconi's syndrome. These changes were also observed in the presence of sodium fluoride and L bromotetramisole, indicating that the modification of phosphorylation was not due to a difference in phosphatase activities. These results suggest that Fanconi's syndrome induced by 4-pentenoate or maleate is not caused by an inhibition of BBM Na(+)-dependent transport systems. Our results also suggest that protein phosphorylation may play an important role in the molecular defect involved in Fanconi's syndrome. PMID- 1493593 TI - Influence of chronic nadolol treatment on blood pressure and vascular changes in spontaneously hypertensive rats. AB - Chronic treatment of spontaneously hypertensive rats (SHR) and Kyoto-Wistar normotensive rats (WKY) with nadolol was carried out from gestation until 28 weeks of age. Nadolol treatment caused some lowering of blood pressure but did not prevent the development of hypertension or cardiac hypertrophy in the SHR, in spite of significant beta-blockade. The lumen of large mesenteric arteries from control SHR was smaller than from WKY, and nadolol treatment increased the lumen size in the SHR. An increased number of smooth muscle cell layers present in the control SHR as compared with WKY was reduced slightly by nadolol treatment. However, the changes produced by nadolol did not reach the levels of control and treated WKY. In the aorta, the incidence of polyploid smooth muscle cells was higher in the SHR than the WKY in the control group. Nadolol treatment reduced the percentage of polyploid cells in both SHR and WKY, so that the difference between these two groups of animals was eliminated in the treated groups. The tissue level of norepinephrine in the plasma, heart, mesenteric arteries, and adrenal glands in the SHR and WKY was not affected by the treatment. We suggest that the ineffectiveness of nadolol in preventing hypertension development may be due to its lack of effect in preventing primary changes in the resistance arteries, and that the development of polyploidy of smooth muscle cells may be mediated by beta-receptors. PMID- 1493594 TI - Regulation of lipoprotein lipase activity in cardiac myocytes from control and diabetic rat hearts by plasma lipids. AB - The objective of this investigation was to test the hypothesis that the diabetes induced reduction in lipoprotein lipase activity in cardiac myocytes may be due to hypertriglyceridemia. Administration of 4-aminopyrazolopyrimidine (50 mg/kg) to control rats for 24 h reduced plasma triacylglycerol levels and increased the heparin-induced release of lipoprotein lipase into the incubation medium of cardiac myocytes. The acute (3-5 days) induction of diabetes by streptozotocin (100 mg/kg) produced hypertriglyceridemia and reduced heparin-releasable lipoprotein lipase activity in cardiac myocytes. Treatment of diabetic rats with 4-aminopyrazolopyrimidine resulted in a fall in plasma triacylglycerol content and increased heparin-releasable lipoprotein lipase activity. Administration of Triton WR-1339 also resulted in hypertriglyceridemia, but the heparin-induced release of lipoprotein lipase from control cardiac myocytes was not reduced in the absence of lipolysis of triacylglycerol-rich lipoproteins. Treatment with Triton WR-1339 did, however, increase the heparin-induced release of lipoprotein lipase from diabetic cardiac myocytes. Preparation of cardiac myocytes with 0.9 mM oleic acid resulted in a decrease in both total cellular and heparin releasable lipoprotein lipase activities. These results suggest that the diabetes induced reduction in heart lipoprotein lipase activity may, at least in part, be due to an inhibitory effect of free fatty acids, derived either from lipoprotein degradation or from adipose tissue lipolysis, on lipoprotein lipase activity in (and (or) release from) cardiac myocytes. PMID- 1493595 TI - Plasma atrial natriuretic factor and atrial wall stress in hypertensive and normotensive rabbits after pacing and volume expansion. AB - Atrial natriuretic factor (ANF) is present in high concentration in atria but in very low concentration in the ventricles. Under conditions of haemodynamic overload ventricular gene expression may become activated, but it is not clear if ventricular ANF can be released through a regulated or constitutive pathway. The purpose of this study was to determine whether basal and stimulated release of ANF are increased in perinephritic rabbits with mild hypertension. Six rabbits were rendered hypertensive by wrapping both kidneys in cellophane, and six sham operated rabbits were used as controls. Eight weeks after renal wrapping, mean arterial pressure was approximately 20 mmHg higher in the experimental group. After anaesthesia, the renal-wrapped group had a higher vascular resistance. Right and left atrial wall stress was measured using sonomicrometry. Volume expansion by 30% of blood volume, using donor blood, caused a small increase in right and left atrial diastolic and systolic wall stress but did not significantly increase plasma ANF. Pacing the heart at 6 Hz caused increases in systolic but not diastolic wall stress and caused a significant increase in plasma ANF; the increase was larger after volume expansion. There were no significant differences between the responses of the experimental and control groups. It is concluded that mild hypertension, in the rabbit, does not lead to changes in atrial wall stress or either basal or stimulated release of ANF. PMID- 1493596 TI - Effect of training and detraining on skeletal muscle glucose transporter (GLUT4) content in rats. AB - The aim of the present study was to examine the effects of treadmill exercise training and detraining on the skeletal muscle fiber type specific expression of the insulin-regulated glucose transporter protein (GLUT4) in rats. GLUT4 protein content was determined by Western and dot-blot analysis, using a polyclonal antibody raised against the carboxy-terminal peptide. Rats were sacrificed 24 h after the last training session. There were no significant changes in muscle GLUT4 after 1 day or 1 week of training. Six weeks of training increased GLUT4 protein content 1.4- to 1.7-fold (p < 0.05) over controls in the soleus and red vastus lateralis, whereas no significant change was evident in the white vastus lateralis muscle. GLUT4 protein content in both soleus and red vastus lateralis muscle returned to near control values after 7 days of detraining. Similar to GLUT4, citrate synthase activity showed no change after 1 day or 1 week of training, increased 1.8-fold over controls after 6 weeks of training, but returned to control values after 7 days detraining. These findings demonstrate that muscle GLUT4 protein is increased in rats with as little as 6 weeks of treadmill exercise training but that the adaptation is lost within 1 week of detraining. It is suggested that expression of the GLUT4 protein is coordinated with the well-documented adaptations in oxidative enzyme activity with endurance training and detraining. PMID- 1493597 TI - Sensory irritation response in mice to sulfur dust. AB - The potential of sulfur dust to produce sensory irritation was evaluated in mice. Male Swiss--Webster mice were exposed by head-only inhalation to 106, 263, or 451 mg/m3 sulfur dust aerosol at room temperature. Breathing frequency and patterns were monitored before, during, and after exposure to evaluate the animal's sensory irritation response to the test atmosphere. Group average breathing rates were decreased 7 and 17% below pretest values in mice exposed to 106 and 263 mg/m3, respectively; however, breathing patterns appeared normal, indicating that there was no sensory irritation. Mice exposed to 451 mg/m3 showed an increase in breathing frequency of 7%, with 1/4 mice displaying very slight signs of pulmonary (deep lung) irritation. Some of the mice in the low- and high-dose groups exhibited signs of slight eye irritation immediately after exposure, but all mice were normal 1 day later. On the basis of these findings, exposure to sulfur dust up to 451 mg/m3 did not produce any sensory or upper airway irritation in mice. PMID- 1493598 TI - All the right moves! Positioning the patient in the OR. PMID- 1493599 TI - So you want to work in the O.R.? PMID- 1493600 TI - Organizational neurotics. PMID- 1493601 TI - Early nasogastric tube removal after abdominal aortic surgery. PMID- 1493602 TI - Journeys and the joy of circles. PMID- 1493603 TI - The unsuspected allergy. PMID- 1493604 TI - Two-dimensional nuclear magnetic resonance studies of an intercalation complex between the novel semisynthetic anthracycline 3'-deamino-3'-(2-methoxy-4 morpholinyl)-doxorubicin and the hexanucleotide duplex d(CGTACG). AB - The complex of the hexanucleotide duplex d(CGTACG) and the antitumor drug 3'-(2 methoxy-4-morpholinyl)-doxorubicin was investigated by two-dimensional 1H nuclear magnetic resonance spectroscopy. After complete assignment of the non-exchanging DNA protons and nearly all drug protons, eight nuclear Overhauser enhancement interactions between drug and DNA were measured at short mixing times. A model was built which shows that the overall structure is very similar to the related daunomycin complex, with the new morpholinyl-substituent extending further into the minor groove of the DNA double helix. The structural information is used for the discussion of the possible formation of DNA-adducts by the new anticancer drug. PMID- 1493605 TI - Arsenic induces and enhances rat hepatic metallothionein production in vivo. AB - Metallothionein genes (MT) are inducible by a variety of agents, including heavy metals. We report the induction of MT expression by arsenite (As3+) in rat liver in vivo. As3+ (but not arsenate [As5+]) injection increased MT protein and MT-1 and MT-2 mRNA accumulation in liver only, but not in kidney or pancreas. In addition, As3+ enhanced zinc-induced MT protein accumulation in liver without any increase in MT mRNA levels. These data indicate that arsenic may increase MT expression either directly (by inducing MT mRNA accumulation), or indirectly by altering post-transcriptional events. This constitutes an unusual mechanism of enhancement of MT gene expression and appears to be mediated by processes not specifically associated with binding of arsenite to MT in vivo. PMID- 1493606 TI - Detection of tobacco smoke carcinogen-DNA adducts in cultured rat buccal mucosa cells following exposure to ethanol and total cigarette smoke condensate or chewing tobacco. AB - Formation of carcinogen-DNA adducts in rat oral epithelial cells after treatment with cigarette smoke condensate (CSC) or chewing tobacco in the presence of ethanol was investigated using the 32P-postlabeling procedure. Concomitant treatment of the cells with ethanol increased the relative adduct level over that found in cells treated with tobacco smoke condensate only. Treatment with chewing tobacco resulted in slightly higher adduct levels than in controls. Treatment of the cells with ethanol did not significantly increase the uptake of a polycyclic aromatic hydrocarbon, benzo[j]fluoranthene, however, high tar CSC alone or in combination with ethanol significantly increased the uptake of radiolabeled benzo[j]fluoranthene, suggesting that increased uptake of the carcinogens may be one of the synergistic mechanisms of alcohol in oral carcinogenesis. PMID- 1493607 TI - Study on the regioselectivity and mechanism of the aromatic hydroxylation of monofluoroanilines. AB - The in vitro and in vivo metabolism of monofluoroanilines was investigated. Special attention was focused on the regioselectivity of the aromatic hydroxylation by cytochromes P-450 and the mechanism by which this reaction might proceed. The results clearly demonstrate that the in vitro and in vivo regioselectivity of the aromatic hydroxylation by cytochromes P-450 is dependent on the fluoro-substituent pattern of the aromatic aniline-ring. Results from experiments with liver microsomes from differently pretreated rats demonstrate that the observed regioselectivity for the aromatic hydroxylation is not predominantly determined by the active site of the cytochromes P-450. To investigate the underlying reason for the observed regioselectivity, semi empirical molecular orbital calculations were performed. Outcomes of these calculations show that neither the frontier orbital densities of the LUMO/LUMO + 1 (lowest unoccupied molecular orbital) of the monofluoroanilines nor the spin densities in their NH. radicals can explain the observed regioselectivities. The frontier orbital densities of the HOMO/HOMO - 1 (highest occupied molecular orbital) of the monofluoroanilines however, qualitatively correlate with the regioselectivity of the aromatic hydroxylation. Based on these results it is concluded that the cytochrome P-450 dependent aromatic hydroxylation of monofluoroanilines does not proceed by hydrogen or electron abstraction from the aniline substrate to give an aniline-NH. radical. The results rather suggest that cytochrome P-450 catalyzed aromatic hydroxylation of monofluoroanilines proceeds by an electrophilic attack of the (FeO)3+ species of cytochrome P-450 on a specific carbon atom of the aromatic aniline-ring. PMID- 1493608 TI - HPLC separation of 32P-postlabelled DNA adducts formed from dibenz[a,h]anthracene in skin. AB - Mouse skin and human skin have been treated in vivo or in short-term organ culture with dibenz[a,h]anthracene (DB[a,h]A), the related 3,4- or 5,6-diols or the anti- or syn-3,4-diol 1,2-oxides. DNA hydrolysates have been 32P-postlabelled and the adducts present examined by HPLC using a phenyl-modified reverse phase column and, for comparison, by PEI-cellulose TLC and autoradiography. The adducts formed when the diol-epoxides were reacted with salmon sperm DNA were also examined. The results show that in mouse skin treated in vivo, the major adducts formed from DB[a,h]A and the 3,4-diol were the same and that two of them were more polar than those formed in skin or in DNA that had been treated with the related anti- or syn-diol epoxides. Human skin treated with DB[a,h]A in culture yielded an adduct profile that was qualitatively similar to the profiles obtained with mouse skin. PMID- 1493609 TI - A comparative binding of platinum anti-tumour compounds to plasma proteins in the rat (in vivo) and mouse (in vitro). AB - Plasma protein binding of 195mPt-labelled cisplatin, carboplatin and iproplatin has been studied in vivo in rat and in vitro in mouse, using both electrophoresis and trichloroacetic acid precipitation. After intravenous injection plasma clearance rates were biphasic for all 3 compounds, (t1/2 alpha, 13-17 min) but cisplatin was retained thereafter longer than the others. By 5 min, gel electrophoresis showed protein labelling with all 3 drugs but none involved low mol.wt. proteins (< 16 kDa). At 2 h a notable proportion of the protein bound platinum was associated with the latter components. There was a general resemblance between the distribution patterns of cisplatin and carboplatin whereas iproplatin showed a persistent retention of the label with time to higher mol. wt. proteins. From in vitro incubation with mouse plasma, rates of interaction respectively were cisplatin t1/2 alpha, 35 min, beta 8 h, carboplatin t1/2, 44 h and iproplatin t1/2, 104 h. By electrophoresis the protein bound fraction pattern (1 h) was again similar for cisplatin and carboplatin with virtually no binding to low mol. wt. proteins. After 24 h these were now involved to a high degree (40%). Iproplatin showed relatively marked binding to proteins of higher mol. wt. but no transfer with time to the low mol. wt. protein zone. A possible explanation is the need for in vivo metabolism for this compound as manifest in the rat. It is suggested that the significance of interaction with low mol. wt. proteins merits further investigation in relation to the antitumour and toxicological actions of these drugs. PMID- 1493610 TI - pH effects on the N-demethylation and formation of the cytochrome P-450 iron II nitrosoalkane complex for erythromycin derivatives. AB - The effects of pH on access to the cytochrome P-450 active site, N-demethylation and formation of the cytochrome P-450 Fe(II)-RNO metabolite complex for a series of erythromycin derivatives were examined. Studies were performed with dexamethasone-treated rat liver microsomes containing large amounts of cytochrome P-450 3A isozymes. In addition to factors such as hydrophobicity or hindrance around the dimethyl-amino function, the ionisation state of the N(CH3)2 group played an important role in the recognition and metabolism of the substrate by cytochrome P-450. Esterification of the desosamine in the beta position of the N(CH3)2 group leads to lower pKa values for the R--N+ H(CH3)2 <--> [R--N (CH3)2] + H+ equilibrium. At physiological pH, the amine group is mainly in the unprotonated form. Consequently, easier access to the protein active site and significant formation of cytochrome P-450 Fe(II)-RNO metabolite complex are observed for these derivatives. These results led us to interpret the formation of cytochrome P-450 Fe(II)-RNO metabolite complex as a series of multiple steps equilibria depending on the ionisation state of the N(CH3)2 group, the partition coefficient of the substrate between the microsomal layer and the aqueous media and a series of metabolic reactions leading partially to the final inhibitory nitrosoalkane-cytochrome P-450 Fe(II) complex. PMID- 1493611 TI - The regioselective binding of CHCl3 reactive intermediates to microsomal phospholipids. AB - Microsomal phospholipids (PL) are a good target for the reactive intermediates produced by either the oxidative or the reductive biotransformation of CHCl3 (Testai et al. (1990), Toxicol. Appl. Pharmacol. 104, 496-503). In order to preliminarily characterize the different PL with CHCl3 reactive intermediates, two common methods of PL breakdown have been exploited: the acid-catalyzed transmethylation and the enzymatic hydrolysis with phospholipase C. The results indicated that radioactivity derived from the adducts of PL with the oxidation metabolite, phosgene, partitioned preferentially in the aqueous phase (the ratio of aqueous to organic phase radioactivity contents was about 10); the opposite occurred (ratio about 0.1) when the PL adducts were produced by the reductive process metabolites (dichloromethyl radicals). Therefore, the two methods of PL adduct breakdown can be used to detect and quantitate selectively the two reactive intermediates of CHCl3 biotransformation. The use of phospholipase C, which specifically cleaves the bond between the glyceryl-oxygen and the phosphor atom of PL also gave some structural information. Indeed, the radioactivity partitioning in the aqueous phase after enzymatic hydrolysis of CHCl3 oxidation associated PL adducts, indicated the selective covalent binding of phosgene residues with the PL polar heads. The clear-cut different partition of radioactivity observed after hydrolysis of PL adducts with CHCl3 reduction intermediates, analogously indicated that dichloromethyl radicals were selectively bound to the PL fatty acyl chains. Using this method we could confirm that in in vitro experimental conditions resembling the physiological status of the liver, both metabolic pathways were concurrently active in hepatic microsomes of B6C3F1 mice. Extents of reactive metabolites similar to those found in B6C3F1 mouse liver microsomes, could be measured in Sprague-Dawley rat liver microsomes only after pretreatment of the animals with PB and incubation with higher CHCl3 concentrations. The toxicological implications of these findings are discussed. PMID- 1493612 TI - Effect of oxidative stress on receptors and signal transmission. AB - Reactive oxygen metabolites affect binding of ligands to membrane receptors and also coupling of receptors to G-proteins and effector enzymes. Peroxidation of membrane lipids may lead to a lowered receptor density and also will alter the viscosity of the plasma membrane, which affects receptor coupling. Reactive oxygen species may also interact with thiol/disulfide moieties on receptor proteins or on other factors in the receptor system, which is responsible for alterations in receptor binding or coupling. Moreover, lipid peroxidation is associated with the phospholipase A2 pathway, which might indirectly affect receptor function. Moreover, oxidative stress may lead to a disturbance in cellular Ca(2+)-homeostasis. This might be related to an effect on Ca(2+) mobilizing receptors, but there is also evidence for a decreased Ca(2+) sequestration by ATPases. In addition, peroxidation of membrane lipids increases membrane permeability to Ca2+. Finally, reactive oxygen species interfere with actions of nitric oxide, thus affecting another pharmacological messenger system. PMID- 1493613 TI - Thermal behavior and elastic properties of phospholipid bilayers under the effect of a synthetic flavonoid derivative, LEW-10. AB - We have investigated the effect on phospholipidic bilayers of LEW-10, a synthetic flavonoid, derivative of diosmin. Two optical techniques, Quasi-elastic Light Scattering (QLS) and Fourier Transform Infrared Spectroscopy (FT-IR) were used. The results show that in the presence of LEW-10, the phase transition of the bilayers is lowered and that the elastic modulus is decreased. The FT-IR results indicate interactions in the aqueous interface regions of the bilayers. We also discuss LEW-10 comparatively with another derivative, LEW-7/S1, whose effect has been previously studied. PMID- 1493614 TI - Modulation of bilayer structures derived from diacetylenic phosphocholines containing oxygen linker beta to diacetylene. AB - Phospholipids with diacetylenes present in the acyl chains form tubules and helices in aqueous dispersions. In order to modulate the morphology of bilayer structures and to understand the role of diacetylene in lipid-bilayer assembly, two diacetylenic phosphocholines, 1,2-bis(9,16-dioxa-hexacosa-11,13-diynoyl)-sn-3 phosph ocholine and 1,2-bis(15-oxa-pentacosa-10,12-diynoyl)-sn-3-phosphocholine, in which the diacetylene is linked to the acyl chain by an oxygen spacer have been synthesized. Lipid dispersions were characterized by calorimetric, film balance and microscopic techniques. Placement of oxygen spacer influences the morphology of the bilayer assemblies formed in aqueous solution. When both ends of the diacetylene were linked to the acyl chain by oxygen atoms, liposomes (diameters ranging from 0.3-3.4 microns) were observed by optical microscopy. Linking only the terminal portion of the acyl chain to the diacetylene with an oxygen atom resulted in a lipid which formed tubular microstructures as well as vesicles. Diameter of the tubular structures ranged from 0.4-4.7 microns. Transmission electron microscopic (TEM) analysis of replicas of a freeze fractured sample of the dispersion revealed that the tubular structures were hollow cylinders consisting of an aqueous core surrounded by a wall of lipid. PMID- 1493615 TI - Implications of a non-lamellar lipid phase for the tight junction stability. Part I: Influence of basic amino acids, pH and protamine on the bilayer-hexagonal II phase behaviour of PS-containing PE membranes. AB - Inverted lipid micelles have been proposed, among other biological functions, to constitute the structural basis of the so-called tight junctions, a special cell cell contact found in epithelia and endothelial, which act as a barrier for the paracellular solute passage. As a model system for the opening and closing of this gate, we investigated the formation of the inverted hexagonal phase (HII phase) in lipid bilayer systems consisting of egg phosphatidylethanolamine (egg PE) and mixed egg PE/bovine brain phosphatidylserine (BBPS) membranes. The formation of the HII phase was modulated by Ca2+ ions, pH, basic amino acids and protamine. The lamellar-HII phase transition temperature TH of pure egg PE membranes at pH 7.0 was lowered with increasing Ca2+ concentration. This effect was attenuated by the presence of 50 mM lysine methyl ester. In the mixed lipid system, this effect was also observed, but even more pronounced. However this effect could be compensated for by raising the Ca2+ concentration from 2 to 10 mM. This was not observed in the pure PE system. In the absence of Ca2+, lysine methyl ester and protamine lowered TH in both monocomponent and mixed lipid systems, whereas lysine caused the opposite effect. The pH-dependence of mixed lipid systems, which were investigated up to a BBPS content of 20 mol%, clearly shows that increasing PS content stabilizes the lamellar phase even at low pH. The results obtained with model membranes are discussed with respect to biological implications of the lamellar-HII phase transition for the modulation of tight junction stability. PMID- 1493617 TI - Training--an opportunity for change. PMID- 1493616 TI - Fusion of lipid bilayers: a model involving mechanistic connection to HII phase forming lipids. AB - A model for the molecular mechanism of the fusion of lipid bilayers is described. A crucial feature of this model and related to the lamellar-->hexagonal phase HII transition is a novel, hypothetical lipid conformation, tentatively referred to here as extended. During fusion this conformation could manifest itself in the contact site between two vesicles in close proximity and involves the extension of the acyl chains of a phospholipid molecule in opposite directions, i.e. embedded into the two opposing bilayers while maintaining the headgroup in the interface. Although evidence for the occurrence of the extended conformation for phospholipids is sparse this conformation appears to be compatible with currently available experimental data. Of importance also is that the extended conformation allows for the fusion of two bilayer membranes to proceed with minimal exposure of the lipid hydrocarbon chains to water. It can also account for other features of membrane fusion such as lipid mixing in the intermediate state without mixing of the vesicle contents as well as for the molecular basis of the action of fusogenic lipids. PMID- 1493618 TI - Functional endoscopic sinus surgery on a day case out-patient basis. AB - One hundred patients, aged 13-79 years, have undergone 195 endoscopic 'ethmoidectomies'. The operative method was entirely based upon the Messerklinger technique. In this study there were two main groups. (1) Patients with moderate to massive nasal/endonasal polyposis. (2) Patients with recurrent sinusitis. In the second group, the preoperative endoscopic findings were dominated by disease in the middle meatus and in the area of the anterior ethmoid, verified either by conventional hypocycloidal or computed tomography. Close to 90% of the patients were treated on an out-patient basis, under local anaesthesia. No serious peroperative complications (major bleeding, CSF leak, or visual problems) have been encountered. Thorough and meticulous post-operative care to avoid adhesions and renewed ostiomeatal obstruction, is felt to be important. The mean follow-up was 14 months. The post-operative results are encouraging, and correspond to larger European and American reports. The Messerklinger technique has proved to be suitable for smaller ENT departments, such as ours, especially as the patients can be treated on an out-patient basis using local/topical anaesthesia. PMID- 1493619 TI - Distribution of eosinophils in the nose in patients with perennial rhinitis. AB - The traditional method of classifying perennial rhinitis into eosinophilic and non-eosinophilic is by taking a single nasal smear from one nostril. In the light of personal experience it was felt that this method of sampling may be inadequate. The present study included 20 patients with perennial rhinitis undergoing nasal surgery. Serum total IgE levels were taken and those above 40 IU/ml had allergen specific IgE measured. Nasal smears and biopsies were taken from 5 sites on each side of the nose; middle and inferior turbinates and post nasal space. The smears significantly correlated with the biopsies (rs = 0.446, P < 0.001). The distribution of eosinophils between and within nasal cavities was found to differ. Representative sampling of the nose is important for accurate eosinophil expression. The definition of an eosinophil rich and poor nose requires greater clarification as it has great clinical relevance regarding management. PMID- 1493620 TI - An evaluation of auricular prosthesis using osseointegrated implants. AB - The purpose of this evaluation is to compare whether retention of auricular prostheses, through utilization of osseointegrated implants rather than by adhesive, provides any improvement in patient acceptance and prosthesis longevity. Forty-seven out of a total of 49 patients having facial prostheses, retained by means of Branemark fixtures, were surveyed. Ease of retention was noted in 91% of the patients. Satisfaction with the shape of the prosthesis, colour and ease of positioning was 100, 85 and 98% respectively. None of the patients experienced skin irritation under the prosthesis and 94% of them wore their prosthesis daily. Of the 13 patients with previous prosthesis experience, 92% stated improved retention and all of them found ease of positioning and wearing comfort had improved. Durability was better in 62%, unchanged in 23% and worse in 15% of these 13 patients. PMID- 1493621 TI - The latissimus dorsi flap in head and neck reconstructive surgery: a review of 121 procedures. AB - The results of a prospective study of 121 latissimus dorsi flaps performed during head and neck reconstructive surgery at the Royal Marsden Hospital are presented. Three-quarters of the flaps were pedicled and one-quarter were free. All the patients underwent surgery for malignant disease. The flap failure rate was 5%, other flap related complications occurred in 19% and the overall rate of complications was 26%. Previous radiotherapy, site of reconstruction, type of flap (free or pedicled) and age of the patient were not significant risk factors. Men were more likely to have a complication than women. PMID- 1493622 TI - Culture of human middle ear mucosal explants; mucin production. AB - Middle ear mucosal biopsies could be maintained in culture for up to 7 days, the longest time attempted in this study. Mucin biosynthesis and secretion were measured by incorporation of 14C-glucosamine. Three peaks of radioactivity were present when the dialysed medium was chromatographed. Peak I which accounted for about 10% of the total radioactivity had properties characteristic of mucin. The other two peaks were not characteristic of mucins. Labelled macromolecules excluded on Sepharose 2B were also present in the tissue. Autoradiography of the explants showed that the labelled glucosamine was concentrated in the epithelial layer. Morphometry demonstrated that 1-2% of the epithelial cell volume consisted of goblet cells. The proportionate incorporation of radioactivity into macromolecules increased with increasing epithelial cell volume. This system will allow assessment of factors implicated in the pathogenesis of otitis media with effusion and the study of the action of pharmacological agents on biosynthesis and secretion. PMID- 1493623 TI - Teflon injection for unilateral vocal cord paralysis and its effect on lung function. AB - We present a prospective analysis of the lung function of 22 patients with unilateral vocal cord paralysis before and after Teflon injection. In the majority of patients the vocal cord paralysis was caused by an underlying malignant condition. Full spirometric and flow-volume loop studies demonstrated an increase in airway resistance after Teflon injection which was not clinically evident. The improvement in symptom score for aspiration was greater than that for dysphonia. PMID- 1493624 TI - A phase II study of cisplatinum versus cisplatinum + nifedipine in end-stage carcinoma of the head and neck. AB - Forty patients with end-stage carcinoma of the head and neck were admitted to a randomized double blind trial with cisplatinum in one arm and cisplatinum + nifedipine in the other. Nifedipine, a calcium channel blocking drug, inhibits the effect of acquired multidrug resistance in animal models. In the present study the addition of this agent had no effect on either response rate or survival in end-stage carcinoma of the head and neck. It is concluded that adding nifedipine to cisplatinum serves no useful purpose in the treatment of end-stage carcinoma of the head and neck. PMID- 1493625 TI - The histopathology of mastoidectomy cavities, with particular reference to persistent disease leading to chronic otorrhoea. AB - Open cavity mastoidectomy remains the principal surgical treatment of middle ear cholesteatoma in the United Kingdom. A significant proportion of mastoid cavities are prone to intermittent or continuous discharge. In this study the histopathological features of material removed from 159 mastoid cavities at revision surgery were reviewed. Findings included squamous epithelium with acute and chronic inflammation, foreign body granuloma and aural polyps. Of particular note was the very infrequent finding of discharging cavities lined with respiratory epithelium, suggesting that retained mucosa in mastoid air cells is not a common cause of persistent otorrhoea. PMID- 1493626 TI - Higher surgical training in Otolaryngology. AB - The views of the membership of the Association of Otolaryngologists in Training (all current UK Senior Registrars and Consultants in their first year of post) were sought on topical aspects of Higher Surgical Training. 80 members (72.3%) participated. The main points to emerge were that the intercollegiate exam is unpopular. 66% feel it is neither well suited to the developing career structure nor a good assessor of trainees, 80% of Senior Registrars for whom the exam is voluntary say they will not sit it, 66% have doubts about the confidentiality of the Specialist Advisory Committee (SAC) interview and 73% felt the need for a separate faculty for Otolaryngology at the Royal College of Surgeons. PMID- 1493627 TI - The radio-opacity of fishbones. AB - Plain radiographs are often taken to localize fishbones which lodge in the pharynx. In this study a pig's neck was used to determine the radio-opacity of 14 different species of fishbones. Radiographs were taken with bones placed in up to four of the common sites of impaction and assessed on two occasions independently by two previously uninvolved ENT consultants. The visibility of the fishbones was scored. Inter and intra-observer agreement for species and site was determined. There was excellent interobserver agreement at both sessions for species (rs1 = 0.96, P < 0.0001, rs2 = 0.95, P < 0.0001) and site (rs1 = 0.98, P < 0.05, rs2 = 0.95, P congruent to 0.05). Intraobserver agreement for species of fish were similarly significant but not for site. The most opaque bones were cod, haddock, grey mullet and lemon sole. The site most often detected was the laryngopharynx and that most often missed was the tonsil. This study is clinically relevant because it is useful to know which species of fishbone are radio-opaque when clinical examination fails to reveal a foreign body and may clarify the decision to proceed to endoscopy. PMID- 1493628 TI - Post-tonsillectomy pain with diathermy and ligation techniques. A prospective randomized study in children and adults. AB - 150 patients (80 children and 70 adults) were entered into a prospective randomized study to compare the post-tonsillectomy pain of unipolar diathermy as opposed to ligation for haemostasis. In children, we found no difference in post operative pain between the diathermy and ligation techniques. However, in adults there was a significant difference, more post-operative pain occurring with diathermy. There was no significant difference in the incidence of secondary haemorrhage. PMID- 1493629 TI - Ingested foreign bodies: patient-guided localization is a useful clinical tool. AB - We prospectively studied the latest 60 patients who presented to the ENT Departments of St Mary's and St George's Hospitals with ingested foreign bodies. Localization of the foreign body by the patient was compared to the actual site of the foreign body at removal and graded accordingly. Localization was better the higher the object. When compared with objects above the cricopharyngeus muscle items impacted below this level were poorly localized (P < 0.0001) and lateralized (P < 0.0001). This suggests that for a patient who is able to lateralize a presumptive foreign body within the cervical region, then that object is likely to be above cricopharyngeus and on the side indicated. Further, it is likely to be visible on indirect laryngoscopy and amenable to removal in the casualty department. We hypothesize that the pharyngeal innervation by the vagus and glossopharyngeal nerves provides better sensation than in the oesophagus which is innervated less densely by the vagus and cervical sympathetic nerves. PMID- 1493630 TI - The relief of snoring by nasal surgery. AB - Patients with nasal obstruction may also complain of snoring. It is uncertain whether surgery which relieves the nasal obstruction will also relieve the snoring. We have reviewed 126 patients who complained of both nasal obstruction and snoring and who underwent nasal surgery. Snoring was completely relieved in 39 patients (31%), was less loud in a further 72 patients (57%), unchanged in 11 and louder in 4. It occurred on fewer nights post-operatively in 61, on the same number in 24 and more frequently in 2. Patients who had nasal polypectomy as part of their nasal surgery obtained the greatest snoring relief. This study suggests that when snoring and nasal obstruction coexist nasal surgery should be considered as the first line of surgical treatment. PMID- 1493631 TI - The morbidity from nasal splints in 105 patients. AB - The results of a randomized prospective trial investigating the morbidity from intranasal splints in 105 patients, were analysed. Intranasal splints are associated with considerable morbidity (significantly greater post-operative pain and a higher incidence of septal perforation and vestibulitis) and although they significantly reduce the likelihood of developing intranasal adhesions, a similar benefit can be obtained by careful nasal toilet at one week. PMID- 1493632 TI - Bacteria and endotoxin in middle ear fluid and the course of secretory otitis media. AB - To determine the influence of bacteria and bacterial products on the course of secretory otitis media (SOM) following ventilation tube insertion we examined 68 middle ear effusions from 57 children with SOM. Swabs were taken for bacteriological examination and the content of endotoxin was measured. The children were followed up for one year and relapse of SOM was recorded. Bacteria were present in 38% of effusions and endotoxin was detectable in 96%. Relapse occurred in 26% of the patients and was related to the presence of bacteria in the original effusion (P < 0.01). The concentration of endotoxin, however, did not correlate with the course of SOM. PMID- 1493633 TI - The use of intra-nasal splints: a consultant survey. AB - A questionnaire was sent to all United Kingdom consultants enquiring about their use of intra-nasal splints. 301 (70%) consultants replied. The commonest reason given for use of nasal splints was to try to prevent the formation of adhesions. Flat, pre-shaped silicone rubber splints were by far the most frequently used type. 64% used splints routinely for operations involving both walls of the nasal cavity. Just over one-third of respondents never or 'rarely' (less than 1 in 50 cases) used splints for procedures involving both walls of the nasal cavity. They reported an adhesion rate of 5.2% which was only 1.3% greater than that reported by those who always or 'sometimes' (at least 1 in 10 cases) used splints. Comments from some respondents and review of the literature suggests that early out-patient review with the use of nasal toilet is an effective alternative to using nasal splints in the prevention of intranasal adhesions. PMID- 1493634 TI - Neck dissection for non-squamous malignancy. AB - Of 1030 patients who underwent neck dissection (radical, modified or selective) in a 27-year period 103 had malignant neck nodes from a primary site in the head and neck with a histological diagnosis other than squamous carcinoma. There were 71 men and 32 women in this group with a mean age of 55 years. 28 patients had neck dissection as part of their initial treatment and 75 for later nodal recurrence. Five-year survival was 52% (40-63%). Survival was site dependent, best for thyroid tumours and worst for tumours of the major salivary glands (chi 1(2) = 6.52, P < 0.05). Histology significantly affected survival, best for papillary tumours and worst for melanoma and undifferentiated tumours (chi 1(2) = 3.85, P < 0.05). Survival was worse with advanced N stage but varied little with node level. The number of nodes invaded had a highly significant effect on survival (chi 4(2) = 23.94, P < 0.001), but extracapsular rupture had no effect. Advanced T stage at the time of surgery had a significant adverse effect on survival using univariate analysis, but this effect disappeared using multivariate analysis. In the 75 patients who had neck dissections for nodal recurrence the presence of a simultaneous recurrence at the primary site had no significant effect on survival. These patients had a better 5-year survival than patients having neck dissection for squamous disease, but the usual predictors of survival in squamous carcinoma do not always apply to non-squamous malignancy. PMID- 1493635 TI - The management of early hypopharyngeal cancer: primary radiotherapy and salvage surgery. AB - Carcinoma of the hypopharynx tends to present late and to occur in old age. Surgical treatment almost always involves a total laryngectomy as well as a major procedure to reconstruct the pharynx. Early tumours up to and including T3 tumours with no, or very early (nodes < 2 cm) nodal disease may be treated with radiotherapy with the option of salvage surgery if recurrence supervenes. In 106 previously untreated patients the 5-year recurrence rate was 50% and the 5-year survival rate was 41%. Sixty-nine patients were referred from other departments because of recurrent disease. The 5-year survival for those patients was 21%. The 5-year survival for those who developed a recurrence at the primary site was 23%. Seventy-eight patients had a resection and 42% suffered a major complication. Only 2 of the methods of reconstruction appear to be satisfactory: for disease confined to the neck free revascularized jejunal loop-repair is effective whereas for more extensive disease gastric transposition is recommended. Twenty-three per cent of patients developed neck node metastases and the 5-year survival rate for patients was 16%. Cox's regression showed that no host or tumour factors predicted survival. At 5 years, 46% of patients were alive with a larynx, 4% were alive without a larynx, 34% were dead of the original cancer and 16 were dead of other causes. PMID- 1493636 TI - Orbital infection secondary to sinusitis in children: diagnosis and management. AB - A series of 18 children with orbital infection secondary to sinusitis is described. The presenting symptoms were headache and periorbital swelling but it was found to be impossible to determine the stage of the orbital infection on clinical grounds. CT scanning can accurately identify the presence of a sub periosteal abscess but both axial and coronal sections may be needed to diagnose abscesses in the superomedial portion of the orbit. Cellulitis may be managed by antibiotic treatment alone, but if an abscess is present it should be drained immediately with a formal ethmoidectomy to decompress the orbit if there is any evidence of reduced visual acuity. PMID- 1493637 TI - Multiple primary malignant tumours in patients with head and neck cancer: the implications for follow-up. AB - The pattern of second primary cancer occurrence in 518 Scottish patients with head and neck cancer was determined by a retrospective study. The overall incidence of second cancers was 9% but the true incidence increased steadily in the years following initial diagnosis to reach a maximum of 21% at 11 years. After 4 years of follow-up patients were more likely to die from a second primary cancer than from the effects of the initial tumour. The Scottish cohort differed from previously reported, overseas, study groups in having a high incidence of second primary cancers in sites outside the upper aerodigestive tract. This potential demographic difference suggests a need for local audit prior to design and implementation of screening protocols for second primary cancers. PMID- 1493638 TI - The diagnosis and treatment of nasal lymphoma, an important cause of upper respiratory tract destruction. PMID- 1493639 TI - Myringoplasty under local anaesthesia: day case surgery. AB - Eleven patients underwent fat graft myringoplasty, using EMLA cream local anaesthetic, as day cases. 10 of them were followed up, and 3 months post operatively, 8/10 (80%) of the perforations were completely closed, with an average improvement of the hearing threshold of 11 dB. All the patients were satisfied with the procedure and it is concluded that fat graft myringoplasty under local anaesthesia as a day case is safe, simple, reliable and cost effective. It should be considered for closure of small perforations (30% or less) of the tympanic membrane. PMID- 1493640 TI - Detection of the Pro664-Leu mutation in the low-density lipoprotein receptor and its relation to lipoprotein(a) levels in patients with familial hypercholesterolemia of Dutch ancestry from The Netherlands and Canada. AB - From a large cohort of hyperlipidemic patients, who attended the Lipid Research Clinic in Amsterdam, The Netherlands and in Vancouver, Canada, 915 consecutive patients with familial hypercholesterolemia (FH) of Dutch descent, were selected. This group of FH patients was screened for the presence of a cytosine to thymidine nucleotide substitution in exon 14 of the LDL-receptor gene, in order to determine the frequency of this mutation in patients of Dutch descent and to investigate the relationship between the mutation and the level of lipoprotein(a). The mutation was detected in seven individuals. All patients with this mutation shared the same haplotype, which is suggestive of an ancient mutation. The index patients and a large kindred with this mutation were further analyzed at the biochemical and clinical level. Except for total and LDL cholesterol, there was no statistically significant difference in biochemical parameters between family members with and without FH. In contrast to previous reports, there was no difference in plasma levels of lipoprotein(a) between patients with the mutation in exon 14 and unaffected individuals. PMID- 1493641 TI - The Wolf-Hirschhorn syndrome in fetuses. AB - Wolf-Hirschhorn syndrome (WHS) with partial deletion of the short arm of chromosome 4 has been exceptionally diagnosed in fetuses. We report prenatal diagnosis of five cases of monosomy 4p. The fetuses were karyotyped for severe intrauterine growth retardation (IUGR) diagnosed on routine ultrasound (US). In addition, cleft-lip and palate and diaphragmatic hernia respectively were found in two cases. The quantity of amniotic fluid was normal in all cases. At autopsy, the fetuses showed the typical craniofacial dysmorphy but without microcephaly. Major renal hypoplasia was the only constant visceral anomaly. Midline fusion defects were observed in all the fetuses, ranging from minor abnormalities such as scalp defect, hypertelorism, pulmonary isomerism, common mesentery, hypospadias and sacral dimple, to cleft palate, corpus callosum agenesis, ventricular septal defect, and diaphragmatic hernia. On post-mortem X-rays, a delayed bone age was always observed. All the placentae were hypotrophic, and two exhibited vascular lesions, although there was no maternal hypertension. Chromosomal studies showed that the breakpoints were within the 4p16 band in three cases, the 4p15 band in one case, and the 4p14 band in one case. The deletion was de novo in four cases, and resulted from a paternal translocation in one case. This study emphasizes the importance of karyotyping all fetuses with IUGR, especially when the quantity of amniotic fluid is normal, and suggests the possibility of recognizing on US the particular phenotype of WHS in utero. PMID- 1493642 TI - Screening for the apolipoprotein B-100 arginine3500-->glutamine mutation in patients with type III hyperlipoproteinemia. AB - Forty-three patients with clinically and biochemically unequivocally defined type III hyperlipoproteinemia (HLP) were screened for the presence of the apolipoprotein (apo) B-100 arginine3500-->glutamine mutation. This receptor binding defective apolipoprotein B variant is the cause of familial defective apo B-100 (FDB), an autosomal dominantly inherited disease, which leads to increased plasma cholesterol levels and premature atherosclerosis. Neither patient expressed FDB. It is concluded that the gene defect responsible for FDB is not involved in the pathogenesis of type III HLP. PMID- 1493643 TI - Autosomal recessive gingival fibromatosis with distinctive facies. AB - Hereditary gingival fibromatosis is a rare condition occurring as an isolated anomaly or as part of a genetic syndrome. The isolated or syndromic disorders are usually inherited in an autosomal dominant manner, but an autosomal recessive form has been suggested. We report on male and female siblings who have gingival fibromatosis in association with specific facial dysmorphism. Their phenotype is depicted and described to document this hitherto unreported autosomal recessive gingival fibromatosis syndrome. PMID- 1493644 TI - Posterior scalp defects in Opitz syndrome. Another symptom related to a defect in midline development. AB - In this report, we describe the presence of a large, posterior scalp defect as another, hitherto nonreported symptom related to a defect in midline development in a 1-year-old boy with Opitz syndrome. PMID- 1493645 TI - Choanal atresia in two unrelated patients with the Coffin-Siris syndrome. PMID- 1493646 TI - Reevaluation of the origin of a marker chromosome in a patient with 47,XX,r(13)(p11q34), + mar by molecular cytogenetics. PMID- 1493647 TI - A Bedouin kindred with 19 piebalds in 5 generations. PMID- 1493648 TI - Staging of oesophageal carcinoma. PMID- 1493649 TI - The Simon nitinol inferior vena cava filter: preliminary experience in the UK. AB - The Simon nitinol filter is one of a new range of inferior vena cava filters designed for percutaneous placement. It employs a thermal memory alloy allowing it to be introduced in a straight form via a 9F sheath when cool but transforming instantly into its predetermined filter shape at body temperature. It was placed rapidly and successfully in six patients via a femoral approach and one patient via an antecubital vein. The only complication was an asymptomatic IVC obstruction in one patient. PMID- 1493650 TI - Thrombolysis of the occluded prosthetic graft with tissue-type plasminogen activator--technique, results and problems in 23 patients. AB - Over a 12 month period all patients but one presenting to our hospital with occluded prosthetic grafts were treated by thrombolysis using local pulsed administration of tissue-type plasminogen activator (t-PA). There were 30 interventions in 23 patients but in one patient no thrombolytic was given after aspiration of pus from the graft. Thrombolysis was attempted in the remaining 29 procedures. 22/29 (76%) of these procedures were performed by direct puncture and catheterization of the occluded graft and in a further six (21%) access was from a non-occluded femoral artery or graft. In one case the graft was accessed surgically. Supplementary angioplasties were performed in 15 cases (52%). Complications requiring surgery occurred in four (14%) with a further seven minor complications. There were no deaths. A lower rate of complications occurred in the grafts entered by direct puncture. Thrombolysis was achieved in all but one case taking an average of only 2.5 h but was only maintained beyond the end of the procedure in 21/29 (72%). An underlying cause for occlusion was identified and treated where possible, e.g. haematological or clotting abnormalities or inflow or outflow stenoses. There was a high rate of reocclusion but with repeat procedures when necessary patency was maintained in 10/22 patients (45%) on follow-up at 1 to 12 months. The best results were obtained with lysis of occluded femoro-femoral crossover grafts. PMID- 1493651 TI - Tuberculosis in HIV positive patients in South Africa: a comparative radiological study with HIV negative patients. AB - The radiological appearances of active tuberculosis in human immunodeficiency virus (HIV) positive patients was reviewed. A study group of 61 Black HIV positive patients and a control group of 50 Black HIV negative patients were analysed. The chest radiographs of the HIV seropositive group showed a significantly higher percentage of lymphadenopathy (50%), pleural effusions (38%) and miliary (8%) or interstitial patterns (11%), as compared with those in the seronegative group (8%, 20%, 0% and 4% respectively). Cavitation (38%) and atelectasis (31%) were less common in the seropositive group than in the seronegative group (82% in each category). Thus in an endemic TB environment an awareness of this difference in appearances will allow the radiologist to alert the referring clinician to the possibility of concomitant HIV seropositivity. PMID- 1493652 TI - Ultrasonography in traumatic splenic rupture. AB - Ultrasound (US) findings and their significance for the clinical outcome were studied in a series of 56 patients hospitalized with a diagnosis of splenic trauma. US was abnormal in 50 cases (89.3%) on admission, revealing intraperitoneal fluid in 41 (73.2%) and a splenic parenchymal injury and/or subcapsular haematoma in 35 (62.5%). US was abnormal in 24/25 patients undergoing urgent surgery, 23/26 undergoing successful non-surgical treatment and 2/5 patients undergoing delayed surgery within 1 to 3 days of a repeat US (abnormal in all five). The presence of intraperitoneal haemorrhage preoperatively was shown accurately by US in 29 cases (96.7%), and the splenic origin of the haemorrhage in 19 (63.3%). Repeat US was of most value for confirming the diagnosis by demonstrating splenic lesions not visible initially. The need for laparotomy could not be predicted on the basis of the US findings alone, however. PMID- 1493653 TI - Ultrasound diagnosis of testicular tumours presenting as epididymal disease. AB - A prospective study of 1494 new referrals for scrotal ultrasound was performed over a 5 year period. In 610 patients referred with a clear clinical diagnosis of epididymal disease, and no clinical suspicion of malignancy, ultrasound diagnosed unsuspected testicular tumours (seven malignant, one benign) in eight patients. In this series one case was counted as false negative for ultrasound diagnosis of tumour, as tumour was the differential diagnosis and not the primary diagnosis. No other patients diagnosed as having benign disease by ultrasound have subsequently been shown to have malignant disease. Sensitivity and specificity of ultrasound for the diagnosis of testicular malignancy in this series is 98% and 99.8% respectively. It is concluded that all patients with scrotal symptoms should be examined by ultrasound in order to achieve the maximal clinical benefit from the early diagnosis of testicular tumours. The implications of this are discussed. PMID- 1493654 TI - Longitudinal stress fracture of the tibia: two cases. AB - Stress fracture of the tibia occurs in individuals who subject their extremities to repeated trauma. They can arise in otherwise healthy bone that is subjected to excessive loads (as in the marathon runner) or in abnormal bone that is subjected to minor loads (as in osteoporosis). These fractures may be anywhere along the tibial shaft and tend to be either transverse or oblique in orientation. We report two cases of stress fracture that ran longitudinally in the distal one third of the tibia. Both patients were healthy and did not describe excessive physical activity prior to fracture. Both describe a repetitive twisting action prior to fracture. Computed tomography was diagnostic in both cases following abnormal bone scans and normal plain radiographs. This unusual pattern of fracture has been reported on only four occasions in five patients in the literature. PMID- 1493655 TI - Technical report: quantitative assessment of diaphragmatic movement--a reproducible method using ultrasound. PMID- 1493656 TI - Case report: percutaneous transluminal angioplasty of the inferior mesenteric artery in the treatment of chronic mesenteric ischaemia. AB - Percutaneous transluminal angioplasty (PTA) of the superior mesenteric artery (SMA) and coeliac axis (CA) is a well recognized form of treatment for patients with chronic intestinal ischaemia and carries a low morbidity and mortality. We report a case where PTA of the inferior mesenteric artery in the presence of occluded SMA and CA proved both feasible and highly effective in abolishing the patient's symptoms. PMID- 1493657 TI - Case report: pneumatosis intestinalis occurring in association with cryptosporidiosis and HIV infection. AB - We report a case of pneumatosis intestinalis (PI) occurring in association with cryptosporidiosis in a patient documented as being HIV-seropositive. Chest and abdominal radiographs taken 2 months previously were normal and the patient did not have any evidence of gastrointestinal infection at that time. The case was complicated by cyst rupture resulting in a pneumoretroperitoneum and pneumomediastinum. The association of pneumatosis and cryptosporidiosis has not been previously reported. PMID- 1493658 TI - Direct puncture venography. PMID- 1493659 TI - [The physiopathological aspects and new therapeutic approaches in cardiac circulatory failure]. AB - Pathophysiological mechanisms are reviewed concerning the onset and the perpetuation of the clinical features of congestive heart failure. This syndrome is a severe condition of poor prognosis and bad life quality which in the last decades has reached, in the western industrial countries, the highest levels of general mortality, mainly due to the high prevalence of hypertensive and ischaemic myocardiopathies in the last years. To the clinical features of heart failure mainly contributes a deregulation of the physiological compensatory mechanisms contemporarily and concurrently activated following the primary deficiency of the heart pump function. In physiological conditions, following the myogenic adapting mechanisms reflex mechanisms intervene, activated by intracardiac and aortic and carotid-sinus mechanoreceptors following the variations in intracardiac and intravascular pressure and generally evoking negative feed-back effects. In patients with heart failure arterial high pressure mechanoreceptors respond to the reduction in effective arterial pressure thus provoking a deactivation of the tonic inhibition on the sympathetic cardiovascular drive. This leads to an activation of peripheral and renal vasoconstrictor tone, to a raised medullary catecholamine incretion, to heart rate and inotropism stimulation, and to an increase in pituitary gland ADH production as well as to an activation of renin-angiotensin-aldosterone system (RAAS). Analogous vasoconstrictive, and sodium and water retentive effects can be elicited by endothelin produced by endothelial cells and found in high plasma levels in CHF. These excitatory effects, leading to a rise in systemic vascular resistance and to hydro-electrolytic retention with volume expansion, are not efficiently counteracted by the opposite effects triggered by cardiopulmonary vagally mediated mechanoreceptors activated by the raised cardiac filling pressure and leading to sympathetic nervous inhibition, peripheral and renal vasodilation, ADH and RAAS inhibition. Analogous effects should be provoked by the raised production, due to enhanced heart wall distension, of atrial natriuretic factor leading to vasodilation, natriuresis and diuresis. Reduced sensitivity of cardiopulmonary baroreceptors and lowered production of ANF due to structural cardiac changes could represent, according to most opinions, the main factors responsible for the prevailing sympathetic activation and hydro-saline retention in CHF. The activation of cardiopulmonary sympathetic positive-feed back afferents, could be also involved in the characteristic alteration of the vago-sympathetic balance in heart failure. The persistent reduction in heart pump function could lead to the instauration of vicious circles among the various regulatory systems and create an overcompensation condition.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1493660 TI - [Preclinical changes in left ventricular function in obesity. An angioscintigraphic study]. AB - Equilibrium pool scintigraphy was performed in 11 obese subjects (BMI 34 +/- 2) and in 14 normal control subjects. Temporal and spatial smoothing of the data was then performed followed by time-activity curve generation using a semiautomatic second derivative edge-detection algorithm. The increase in counts during the first third of diastole divided by the total change in number of counts during diastole was determined as the one-third filling fraction. This index of diastolic filling was significantly decreased in obese subjects as compared to the control group. These findings indicate that diastolic abnormalities may be an early finding in obesity-linked heart disease, occurring in the presence of normal systolic function (E.F. = 65 +/- 5%). PMID- 1493661 TI - [The clinical and hemodynamic effects of propionyl-L-carnitine in the treatment of congestive heart failure]. AB - In order to evaluate the clinical and hemodynamic effects of propionyl-L carnitine (PLC) a randomized, double-blind study versus placebo was performed in 50 patients of both sexes, between 48 and 69 years of age, affected by mild moderate congestive heart failure. All patients participating in said study were on digitalis and diuretic treatment. 25 of these belonged to the control group, while the other 25 were treated with an oral dose of 1 g b.i.d of propionyl-L carnitine. At the end of six months of treatment maximum exercise time on the treadmill increased 11.1% after 90 days and 16.4% after 180 in the group treated with PLC. From a hemodynamic standpoint, after 30, 90 and 180 days the ejection fraction increased by 7.3%, 10.7% and 12.1%. At the same time, moreover, the systemic vascular resistances were reduced by 14.9%, 20% and 20.6%. In the patients treated with placebo, however, the above-mentioned parameters showed no significant variation. Finally, no unexpected events or toxic effects were observed in any of the patients in either group. As a consequence of these results it is possible to affirm that propionyl-L-carnitine, due to its clinical and hemodynamic effects, represents a drug of notable therapeutic interest in patients with congestive heart failure, in whom it may be usefully combined with the usual pharmacological therapy. PMID- 1493662 TI - [The general theory of systems and the microcirculation]. PMID- 1493663 TI - [A comparison between intraurethral echography, computed tomography and magnetic resonance in the staging of bladder tumors]. AB - The purpose of our study was to assess the utility of CT and MRI in the staging of bladder carcinoma. The overall accuracy of MR is in the range of 66 to 85%. T2 weighted and post-Gadolinium T1 weighted images allow one to differentiate T1-T2 from T3a type of neoplasms. Perivesical fat invasion is well shown with T1w images while pelvic wall invasion is better seen on T2w--images. The overall accuracy of CT ranges from 64 to 92%. CT cannot distinguish stage T1 from stage T3a tumors CT is accurate for demonstrating perivesical fat invasion. In the assessment of lymph node metastases CT and MRI have low sensitivity but high accuracy. Trans-urethral sonography is more accurate than CT and MRI in the staging of parietal invasion and it permits the differentiation between T1, T2 and T3a stages even though the distinction between T2 and T3a type of tumors is not always possible. Trans-urethral sonography is not useful in assessing extravesical extension and lymph node metastases. In summary, trans-urethral sonography is the method of choice for evaluating parietal invasion. CT and MR are very accurate for evaluating perivesical fat invasion and are also quite accurate for evaluating lymph nodes. MRI is superior to CT in distinguishing tumors limited to superficial muscle from those that invade deep muscle. MRI can also be helpful in distinguishing the tumor from fibrosis and edema. PMID- 1493664 TI - [Intestinal volvulus in pregnancy]. AB - Intestinal occlusion is a rare pathologic event during pregnancy occurring mostly in the second and third trimenon when increased volume of the uterus and the consequent displacement of abdominal organs cause complications of pathologies which would otherwise escape notice, such as intestinal adhesions, to become manifest. Diagnosis is difficult for a number of reasons. Vomiting during the first trimenon and mild abdominal pain during the third are often neglected or considered to be part of the normal course of pregnancy; pain is sometimes referred to atypical sites due to the displacement of abdominal organs; in other cases, the high endorphin tonus is apt to reduce the customary defence reaction. All this should not cause time to be lost, and whenever intestinal occlusion is suspected all the necessary diagnostic procedures must at once be carried out and appropriate therapy must speedily be started so as to reduce the risk of mortality and morbidity for mother and fetus. Management of ileus in pregnancy is identical to that for the non pregnant woman, except for the need to empty the uterus in cases in which it prevents treatment or if the fetus has reached a sufficient degree of pulmonary maturity. The paper describes a case of ileal volvulus and revisits the literature analyzing the diagnostic and therapeutic options suggested. PMID- 1493665 TI - [Cardiac and renal sodium-modulating hormones in juvenile arterial hypertension. The physiopathological aspects and therapeutic results of a trial at the Policlinico Militare Celio in Rome]. AB - Sodium balance plays a primary role in blood pressure regulation. Atrial natriuretic peptide, a recently discovered natriuretic substance, seems to participate in renal sodium handling, but its behavior in essential hypertension has not been fully defined. In our study, to avoid the "contamination" of factors other than hypertension, we evaluated the plasma levels of atrial natriuretic peptide in young men at military draft age. Our main results showed that plasma atrial natriuretic peptide levels are higher in young hypertensives with low plasma renin activity and low urinary excretion of active kallikrein. The influence of a positive genetic background for essential hypertension on plasma atrial natriuretic peptide levels was also investigated. Our data showed slightly elevated levels of the atrial hormone in young normotensives with a family history of hypertension. PMID- 1493666 TI - [The efficacy and tolerance of heparin-calcium at low doses in postinfarct ischemic cardiopathy]. AB - The above study was undertaken in order to evaluate the efficacy and tolerability of low dose calcium heparin for postinfarct ischemic heart disease (CIPI). In particular, the incidence was checked of: cardiovascular death, reinfarction, angina pectoris, TIA or RIND, stroke, arterial thromboembolism, venous thromboses, heart failure, complex ventricular arrhythmias, silent myocardial ischemia. Eighty patients with CIPI were divided into two groups similar for age, sex, physical features, cardiovascular risk factors, site of infarction, length of hospitalization, complications during hospitalization, clinical and instrumental findings at discharge, concomitant pathology. Upon discharge, patients were randomized into group 1 for traditional treatment and group 2 which in addition received 12,000 U calcium heparin s.c. every 24 h. After 12 months, during which patients were submitted to periodical laboratory and instrumental (standard and dynamic ECG, echoG) evaluation, group 2 had significantly fewer cardiovascular events than group 1 both as to overall number of events and as to number of events per individual patient. Especially, silent myocardial ischemia and ventricular arrhythmias were less frequent in group 2 patients and these two events, especially if coincident, are known to have severe prognostic implications. The efficacy of low-dose calcium heparin must be attributed to the enhancement of physiological antithrombotic mechanisms with compensation of blood clotting disorders that are fairly frequent in CIPI patients. Long-term s.c. administration was well tolerated. PMID- 1493667 TI - [Atherosclerosis: the risk factors]. AB - A group of 196 outpatients among whom 112 non-insulin-dependent diabetics were divided into 4 subgroups according to whether they had vascular disorders or not. For statistical evaluation by means of correlation coefficient and chi-square test both risk factors (smoking, family history, arterial hypertension, BMI) and laboratory values (total and HDL cholesterol, triglycerides, fibrinogen, HbA1c, factor VIII, PF4, BTG) were taken into account. Our findings confirm the relevance of risk factors and the need for diabetic patients to be metabolically well balanced; PF4, BTG, and factor VII were normal in all patients which suggests that these are not suitable, as far as the present study is concerned, to be considered markers of vascular disorders. An interesting correlation was found between these factors and serum triglycerides, especially in the subgroup of diabetics with vascular disorders. An interesting finding was the increase of fibrinogen in subjects with vascular disorders especially in non-diabetics. PMID- 1493668 TI - [Ketanserin, an antagonist of 5-HT2 serotoninergic receptors and free-radical scavenger]. AB - The authors describe an original clinical method of auscultatory percussion which is easily performed and reliable for bedside evaluation of tissue Co Q10, tissue acidosis, endothelial damage, free radicals and microcirculatory functional reserve. They report data observed in 25 arteriosclerotic patients treated with ketanserin which show the drug to be an excellent scavenger of free radicals. PMID- 1493669 TI - [Captopril versus placebo in the prevention of hemicrania without aura. A randomized double-blind study]. AB - Endogenous opioids are known to be involved in the pathophysiology of idiopathic headache. In fact, decreased levels of enkephalin (E) or endorphin (BE) during headache attacks might be a marker of an altered pain-inhibiting system of central neurotransmission or could be secondary to alterations of brain circulation that often occur during the headache crisis. Recently, captopril (C) has been shown to be apt to restore the availability of endogenous opioids, to improve cerebral blood flow via the inhibition of both the cerebral and systemic renin-angiotensin system or of catecholamine release. It has also been reported to be able to restore the nociceptive-antinociceptive balance through an increase of serum kinin (K) or prostaglandin (Pr) levels. In the present study, the efficacy of C in reducing the frequency (F), duration (D), or severity (S) of headache paroxysm were investigated in a double blind trial vs. placebo (P). Twenty-six subjects (5 males and 21 females; mean age 37 +/- 11 years) suffering from idiopathic headache at least for one year have been allocated to treatment with C (25 mg three times/day) or P according to a double-blind randomized protocol for 4 months. The effects of C or P have been evaluated with Migraine Index Correct, related to changes in F, D or S of headache attacks. Our results indicate that C is effective in reducing F, D or S in subjects with idiopathic headache. PMID- 1493670 TI - [Median-term (4 months) treatment with glibenclamide + metformin substituting for glibenclamide + fenformin lowers the lacticemia levels in type-2 diabetics (NIDDM)]. AB - 60 NIDDM patients, mean age (68 +/- 3 years), BMI (25 +/- 5.1 kg/m2), fasting blood glucose (FG) (170 +/- 10 mg/dl), mean daily blood glucose (MDBG) (180 +/- 10 mg/dl), daily glycosuria (GLU) (15.6 +/- 9 g/24 hours), HbA1c (7.9 +/- 0.6%), basal (1.2 +/- 0.2 ng/ml) and stimulated (3.89 +/- 1.3 mg/ml) C peptide (CP) treated by ASS (7.5 +/- 75 mg), after a strict 4 months follow-up period, were assigned to G + M treatment (7.5 +/- 1.500 mg) during a 4 months period. During G+M treatment FG (171 +/- 13 at t0 to 165 +/- 11 mg/dl: p < 0.01 at t4) varied significantly. MDBG (180 +/- 10 at t0 to 175 +/- 12 mg/dl at t4:p < 0.05), GLU (16 +/- 9 at t0 to 11 + 6 g/24 hours at t4; p < 0.01), HbA1c (8.1 +/- 0.4 at t0 to 7.6 +/- 0.3% at t4; p < 0.01). Basal CP remained unchanged in G+M period and varied significantly during ASS period (1.3 +/- 0.3 ng/ml at t4; p < 0.01) and stimulated CP (unchanged during ASS) was reduced during G+M (4.19 +/- 0.4 to 4.04; p < 0.05). Highly significant variations were observed for LAC (28.4 +/- 2.1 at t0 to 14.9 +/- 0.6 mg/dl: p < 0.01 during G+M treatment). G+M therapy was found to be more effective and safer than ASS therapy in regard to glucose metabolism and lactate production in a selected group of NIDDM patients. PMID- 1493671 TI - [Computed tomography and magnetic resonance in the TNM staging of pulmonary carcinoma]. AB - On the basis of a review of the literature and of the authors' personal experience, the usefulness was evaluated of CT and MR for the staging of lung carcinoma. Neither method was found to be useful for diagnosis; as to staging, neither is capable to distinguish between simple adhesion and infiltration of adjacent structures by the tumor. As compared to CT, MR has the advantage of showing many layers and better contrast resolution but spatial resolution is poorer. MR was superior to CT for the study of hilar lesions (easily differentiated from vessels) and for those involving the upper pulmonary sulcus. The accuracy of evaluation of the N parameter was the same for both methods whereas for the M parameter RM was more accurate than CT. Considering the wide margins for technological improvement of MR, a more important role for this method compared to CT can be hypothesized. PMID- 1493672 TI - Therapeutic alternatives for postmenopausal osteoporosis. PMID- 1493673 TI - Rocky Mountain spotted (and spotless) fever. PMID- 1493674 TI - Constipation. PMID- 1493675 TI - Hormone replacement therapy for menopausal women. PMID- 1493676 TI - Influenza: update. PMID- 1493677 TI - Current method of management of rheumatoid arthritis. PMID- 1493678 TI - Sports-related injuries in children and young adults. PMID- 1493679 TI - Diabetes mellitus in the 1990's: can complications be prevented? PMID- 1493680 TI - Influence of area of application of allergen on sensitization in contact dermatitis. AB - There are at least 2 quantitative variables when applying allergens to obtain sensitization: the absolute amount of allergen and the surface concentration. This review analyzes the limited studies on surface concentration and determines surface area threshold levels for the allergens documented in the literature. PMID- 1493681 TI - Photosensitivity to piroxicam: absence of cross-reaction with tenoxicam. AB - We studied 2 groups of patients. One group of 10 patients had a photosensitive eruption to piroxicam. Another group of 24 patients had positive patch test reactions to thimerosal and thiosalicylic acid and had never taken piroxicam or tenoxicam. Patients were patch tested with thimerosal 0.1% pet., thiosalicylic acid 0.1% pet., salicylic acid 2.0% pet., piroxicam 1 and 5% pet. and tenoxicam 1 and 5% pet. Photopatch tests were also performed with piroxicam and tenoxicam. All 10 patients with photosensitivity to piroxicam had positive patch tests to thimerosal and thiosalicylic acid and 9 of them had positive photopatch tests to piroxicam. 20 out of 24 patients with positive patch tests to thiosalicylic acid also had positive photopatch tests to piroxicam. All the patients tested with salicyclic acid were negative. Out of the 29 patients with positive photopatch tests to piroxicam, none reacted to tenoxicam. In countries with a high incidence of contact sensitivity to thimerosal/thiosalicylic acid, the use of piroxicam should be avoided and replaced by tenoxicam, a drug without reported photosensitivity. PMID- 1493682 TI - Dithranol allergy: fact or fiction? AB - A case of a psoriatic patient allergic to dithranol and coal tar is described. It is suggested that dithranol 0.001% pet. is a suitable concentration to test for dithranol allergy, as higher concentrations may produce irritant reactions. The literature on dithranol allergy is reviewed and the frequent simultaneous reactions to dithranol and coal tar discussed. PMID- 1493683 TI - Changes in transepidermal water loss and cutaneous blood flow during the menstrual cycle. AB - This study quantified irritant susceptibility and blood vessel reactivity in normal women over the course of the menstrual cycle. Such alterations were studied by observing vasodilation from topical application of methyl nicotinate (MN) on the following days of the menstrual cycle: (i) the day of putative maximal estrogen secretion; (ii) the day of maximal progesterone secretion; (iii) the day of minimal estrogen/progesterone secretion. These responses were evidenced by changes in the following dose response characteristics: the initial response (IR), the peak response (PR) and the area under the curve (AUC). Baseline laser Doppler velocimetry (LDV) blood flow values and transepidermal water loss (TEWL) values on normal skin were also obtained. No significant differences existed for any of the dose-response characteristics (IR, PR, AUC) when the values for the 3 testing days were compared to one another. Significant differences did exist for baseline TEWL values when comparing the day of maximal estrogen secretion to the day of minimal estrogen/progesterone secretion. TEWL was higher on the day of minimal estrogen/progesterone secretion as compared to the day of maximal estrogen secretion on both back (p = 0.037) and forearm (p = 0.021) sites, suggesting that the skin barrier function is less complete on the days just prior to the onset of the menses as compared to the days just prior to ovulation. Significant differences in baseline blood flow also existed for the day of maximal estrogen secretion as compared to the day of maximal progesterone secretion, with higher baseline blood flow recorded on the day of maximal progesterone secretion on both the back (p = 0.021) and forearm (p = 0.009) sites. PMID- 1493684 TI - Permeation of chromium salts through human skin in vitro. AB - Chromium permeation studies were performed on full thickness human skin in diffusion cells. All samples were analysed for the total chromium content by graphite furnace Zeeman-corrected atomic absorption spectrometry. Some samples were analysed by an ion chromatographic method permitting the simultaneous determination of Cr(VI) and Cr(III) as well. The amounts of chromium found in all skin layers were significantly higher when potassium dichromate was applied to the skin compared with chromium chloride or chromium nitrate. Chromium could only be detected in the recipient phase after application of the dichromate solution. Chromium skin levels increased with increasing concentrations of applied chromium salts up to 0.034 M Cr. The amount of chromium in recipient phase and skin layers increased with increasing pH when the applied solution contained potassium dichromate. This was ascribed to a decreased skin barrier function of the skin. The amount of chromium found in all skin layers after application of chromium chloride decreased with increasing pH due to lower solubility of the salt. The % of chromium found in the recipient phase as chromium(VI) increased with increasing total chromium concentration indicating a limited reduction ability of the skin in vitro. PMID- 1493685 TI - Occupational dermatitis in the aircraft industry: 35 years of progress. AB - A comparison of the occupational dermatitis occurring in the same aircraft factory during 2 separate decades, 1955-1965 and 1981-1990, is presented. Subungual pulpitis is highly specific to this industry, because of the handling of resins and sealing agents. The number of cases dropped from 122 to 40, in accordance with progress in preventive medicine and technological changes in the factory. Irritant contact dermatitis nevertheless remained appreciable, while allergic contact dermatitis greatly decreased. PMID- 1493686 TI - In vitro evaluation of water and petrolatum as vehicles in chromate patch testing. PMID- 1493687 TI - Anaphylaxis due to a latex vaginal vibrator. PMID- 1493688 TI - Textile dye dermatitis. PMID- 1493689 TI - Cross-sensitization to mometasone furoate in patients with corticosteroid contact allergy. PMID- 1493690 TI - Structural specificity of carbamazepine-induced dermatitis. PMID- 1493691 TI - Results of patch testing in children. PMID- 1493692 TI - Occupational contact allergy to benzydamine hydrochloride. PMID- 1493693 TI - Contact hypersensitivity to azathioprine. PMID- 1493694 TI - Allergic contact dermatitis from nickel with unusual localization. PMID- 1493695 TI - Echographic evaluation of edema induced by patch test chambers. PMID- 1493696 TI - Allergic contact dermatitis from garlic. PMID- 1493697 TI - Contact dermatitis from natural latex. PMID- 1493698 TI - Contact dermatitis caused by allergy to ophthalmics: an update. PMID- 1493699 TI - Anaphylactic reaction to unexpected latex in a polychloroprene glove. PMID- 1493700 TI - 3 cases of contact dermatitis from alkylammonium amidobenzoate (Osmaron B). PMID- 1493701 TI - Allergic dermatitis due to oral ranitidine. PMID- 1493702 TI - Allergic contact dermatitis in a photographer. PMID- 1493703 TI - Occupational fibreglass dermatitis in Hong Kong. PMID- 1493704 TI - Airborne contact dermatitis from the woods Acacia melanoxylon and Entandophragma cylindricum. PMID- 1493705 TI - Consecutive patch testing with sodium sulfite in eczema patients. PMID- 1493706 TI - Allergic contact dermatitis from Kathon 893. PMID- 1493707 TI - Contact dermatitis due to henna, solvent red 1 and solvent red 3. A case report. PMID- 1493708 TI - Contact sensitivity to thiram in wooden shoes. PMID- 1493709 TI - Combined immediate and delayed hypersensitivity to mezlocillin. PMID- 1493710 TI - FDA requirements for nonclinical testing of contraceptive steroids. AB - Written guidelines for the preclinical testing of contraceptive steroids have not been revised since 1968 despite the fact that many important changes have been implemented by the FDA's Division of Metabolism and Endocrine Drug Products. This paper describes the new preclinical testing requirements and the rationale for their implementation. PMID- 1493711 TI - Acceptability of a new intravaginal barrier contraceptive device (Femcap). AB - A comprehensive questionnaire to assess acceptability was sent to 106 participants (and their partners) in a study on the safety and effectiveness of the Femcap. Participants were asked to rate their satisfaction with various aspects of the method, and were also asked about complaints such as vaginal infections, urinary tract infections, or other irritation. Eighty-one percent of the study sample either returned the mailed questionnaires or completed telephone interviews. Results were encouraging in that none of the study subjects or their partners reported any discomfort, trauma, or interference in sexual spontaneity with the cap. Vaginal irritation and infections were infrequently reported. The feature best liked by most participants was the absence of hormones associated with the method; the feature least liked was removal of the device. The Femcap may be an acceptable alternative to currently available barrier contraceptive devices. PMID- 1493712 TI - A comparison of open-end versus closed-end vasectomies: a report on 6220 cases. AB - This study was done to determine if there was a difference in results when both vas ends were closed or when the prostatic end was closed and the testicular end left open. The author performed 6220 vasectomies between June 1, 1972 and June 1, 1992. The first series consisted of 3081 vasectomies in which both ends of the vas deferens were closed. The second series consisted of 3139 vasectomies in which the testicular end of the vas deferens was left open while the prostatic end only was closed. No portion of the vas was excised. Congestive epididymitis was diagnosed in 6% of cases utilizing closed-end vasectomy and 2% of cases where the open-end vasectomy was performed. Open-end vasectomy is recommended because the incidence of congestive epididymitis is reduced. PMID- 1493713 TI - The immobilization of all spermatozoa in vitro by bitter lemon drink and the effect of alkaline pH. AB - This study investigated the effects of increase in temperature and in pH of Coca Cola, Afri-Cola, Pepsi-Cola and Krest bitter lemon drinks ("soft drinks") produced in Nigeria on the in vitro motility of spermatozoa. Semen was collected from 7 men, average age 28 years, of proven fertility, after 5 days' abstinence from sexual intercourse. The temperature and pH of the drinks were adjusted from 22 degrees C (room) to 37 degrees C, and pH 2.4 (acid) to 7.5 (alkaline), respectively. The mean % motility of spermatozoa in the adjusted and in the unadjusted drinks was compared for significant differences at the 1% level using the student's t-test. The results showed no significant differences in mean % motility in the drinks at 22 degrees C and at 37 degrees C. The mean % motility in all the drinks, except Coca-Cola, was significantly greater at alkaline than at acid pH; for Coca-Cola, motility was significantly greater at acid than alkaline pH. Of the drinks, Krest bitter lemon (unadjusted) immobilized all spermatozoa within 1 minute of addition. CONCLUSION: i) alkalinity decreases the spermicidal action of all drinks except Coca-Cola, and ii) Krest bitter lemon may achieve very high efficacy if used as post-coital douche, especially in the impoverished, densely populated Third World. PMID- 1493714 TI - Plasma prolactin in relation to menstrual cycle phase, oral contraceptive use, arousal time and smoking habits. AB - The study was designed to investigate if modern low dosage combined oral contraceptives were associated with changes in plasma prolactin levels in healthy nulliparous women aged 19-25. Plasma prolactin was not significantly correlated to oral contraceptive use, nor to smoking habits. Plasma prolactin was, however, significantly negatively correlated to time since awakening. A significant two way interaction on prolactin was also seen between smoking and present oral contraceptive use. In our material the mean values of plasma prolactin were higher in the follicular phase than in the luteal phase, although not significantly. PMID- 1493715 TI - Descriptive epidemiology of induced abortion in Italy 1979-1990. AB - Trends of induced abortions in Italy from 1979 to 1990 have been analysed in terms of overall age-standardised rates and ratios, and according to various characteristics of the women. Temporal trends were characterised by an increase of rates from 11.3/1,000 women aged 15-49 in 1979 to 16.5 in 1982 and then followed by a steady decrease to 11.1/1,000 in 1990. Ratios increased from 228/1,000 livebirths in 1979 to 389 in 1984 and then declined to 286 in 1990. Thus, the overall declines from the early 1980's to 1990 were 33% in rates and 26% in ratios. The same pattern was followed by rates and ratios in various age groups. The highest rates were observed in women aged 25-29 years (27.0/1,000 in 1982 and 17.9/1,000 in 1988) and 30-34 years (25.5/1,000 in 1982 and 19.0/1,000 in 1988), and the lowest ones were in women aged 45-49 (1.0/1,000 in 1982 and 0.8/1,000 in 1988). Ratios reached the highest values in 1984 in most age groups, particularly in women between 40 and 49 years and under 20 years. Ratios increased constantly with number of previous deliveries. At all levels of education, a decline in rates has been observed since 1982, but in the highest educational level, the decline started earlier and was more substantial. The decline in rates among more educated women from 1982 to 1987 was 36%, but it was only 9% among less educated ones. Scope for further preventive action is indicated by the differences according to education and by the slowing down of the decline in the more recent years. This preventive intervention should be focused particularly to women of lower educational level and to those with two or more births. PMID- 1493716 TI - Dihydrospirorenone (ZK30595): a novel synthetic progestagen--characterization of binding to different receptor proteins. AB - Dihydrospirorenone (6 beta, 7 beta, 15 beta, 16 beta-dimethylen-3-oxo-17a-pregn-4 en-21, 17-carbolacton) is a new type of progestin with no other agonistic activities, in particular no estrogenic, androgenic or glucocorticoid activity. Dihydrospirorenone is a potent aldosterone antagonist 8 times as potent as spironolactone and antiandrogenic (0.3 times cyproterone acetate). The aim of the present study is to make a broad characterization of dihydrospirorenone at the receptor level and to discuss the results in comparison to those of established progestins. Kinetic studies of 3H-dihydrospirorenone uptake show a rapid increase in the amount of specific binding during the first three hours. The dissociation of 3H-dihydrospirorenone from the cytoplasmic human uterine progesterone receptor, measured by displacement of labeled steroid with dextran-coated charcoal treatment at 4 degrees C at various times, showed a monophasic or one component, first order dissociation curve like progesterone. Sucrose density gradient centrifugation of the 3H-dihydrospirorenone-labeled myometrial cytosol showed that the dihydrospirorenone binding components sedimented in the 4S and 8S region which is typical for the progesterone receptor under low salt conditions. The high binding affinity of dihydrospirorenone to the binding sites of the mineralocorticoid receptor of rat kidney with an RBA value of 230% compared to aldosterone is remarkable. This reflects the strong antimineralocorticoid activity of this compound which was evaluated in adrenalectomized rats. Furthermore, competitive studies indicated that dihydrospirorenone also displays high affinity for the androgen and some affinity for the glucocorticoid receptors but no measurable affinity for the estrogen receptor. PMID- 1493717 TI - Return to fertility after removal of a levonorgestrel-releasing intrauterine device and Nova-T. AB - In a European randomized multicenter study, the efficacy and safety of an intrauterine contraceptive device releasing 20 microgram levonorgestrel/24 hours (LNG-IUD) have been evaluated and compared to the Nova-T. Because the LNG-IUD has a strongly suppressive effect on the endometrium and in some women affects ovarian function, the return to fertility after removal of the IUD was studied. Two-hundred-nine women (71 in the Nova-T and 138 in the LNG-IUD group), who had their IUDs removed because of planning pregnancy, were followed at least 24 months or until termination of pregnancy. For the Nova-T, the cumulative conception gross rate was 71.2/100 women after 12 months (79.7 after 24 months) and for the LNG-IUD 79.1 (86.6 after 24 months). The difference between the devices is not statistically significant, and in spite of the endometrial suppression during use of LNG-IUD, there is no delay of return to fertility and in both groups 96% of the pregnancies occurred during the first year after removal of the device. Eighty-four % of the pregnancies in the Nova-T group and eighty-six % in the LNG-IUD group ended in live births. The results suggest that the endometrium recovers quickly, normal ovulations are established and the fertility seems to be unaffected after use of an LNG-IUD. PMID- 1493718 TI - Muscle amino acid and protein metabolism in chronic renal failure. PMID- 1493719 TI - Metabolic and nutritional abnormalities in kidney disease. Proceedings of the Scientific Meeting of the European Study Group for the Conservative Management of Chronic Renal Failure. Trieste, Italy, September 5-7, 1991. PMID- 1493720 TI - Altered cellular host defence in malnutrition and uremia. PMID- 1493721 TI - Apolipoprotein B-containing lipoprotein particles in progressive renal insufficiency. PMID- 1493722 TI - Therapy of systemic hypertension in chronic renal failure. PMID- 1493723 TI - Angiotensin converting enzyme inhibitors and calcium antagonists in the progression of renal insufficiency. PMID- 1493724 TI - Mechanisms of progression of diabetic nephropathy. Conclusions based on clinical observations. PMID- 1493725 TI - Dietary compliance in the trial of the European Study Group. An interim analysis. European Study Group for the Conservative Management of Chronic Renal Failure. PMID- 1493726 TI - Dynamic evaluation of renal function in subjects with solitary kidneys. PMID- 1493727 TI - Dietary treatment of type I diabetic nephropathy with renal insufficiency. PMID- 1493728 TI - Role of essential amino acids and ketoanalogues in antagonizing uremic catabolism. PMID- 1493729 TI - Approaches to correcting protein malnutrition with modified peritoneal dialysis solutions. PMID- 1493730 TI - Factors affecting nitrogen balance in hemodialysis patients. PMID- 1493731 TI - Amelioration of cardiac function by L-carnitine administration in patients on haemodialysis. PMID- 1493732 TI - Effects of L-carnitine supplementation in the dialysate on serum lipoprotein composition of hemodialysis patients. PMID- 1493733 TI - Branched-chain amino acids and branched-chain ketoacids in uremia. PMID- 1493734 TI - Metabolic alterations in acute renal failure. PMID- 1493735 TI - Alterations in skeletal muscle ion and amino acid transport in chronic renal failure. PMID- 1493736 TI - Effects of erythropoietin administration on nutritional state and erythrocyte metabolism in maintenance hemodialysis patients. PMID- 1493737 TI - Water- and fat-soluble vitamin status in chronic renal insufficiency patients. PMID- 1493738 TI - Severity of anaemia influences pattern of amino acids and alpha-keto acids in haemodialysis patients. PMID- 1493739 TI - House dust mites. Introduction. PMID- 1493740 TI - Special issue: house dust mites. Dedicated to Professor Alex Fain M.D. PMID- 1493741 TI - Storage mites. AB - The interest in allergy to storage mites has increased over the past few years. Storage mites feed on a variety of substances and they can be found in many different products such as grain, flour, hay and straw, but also in house dust samples. The more common genera are Lepidoglyphus, Tyrophagus, Glycyphagus, Acarus and Blomia. Several species of storage mites have been shown to cause IgE mediated sensitization among rural workers, who to a varying extent develop asthma, rhinitis or conjunctivitis when exposed to barn dust. However, a number of studies have reported on sensitization to storage mites also among urban people, indicating that sensitization is not restricted to individuals with occupational exposure. Regarding the allergenic relationship between storage mites and house dust mites, there appears to be a limited allergenic cross reactivity between the two species. However, both species also possess their own unique allergens. Further research on identification and characterization of storage mite allergens and their cross-reactivity is required to understand the complexity of epitopes and allergens. PMID- 1493742 TI - A review of recent immunochemical studies of Blomia tropicalis and Euroglyphus maynei allergens. AB - Exposure to mites other than Dermatophagoides spp., particularly Blomia tropicalis and Euroglyphus maynei, has been increasingly recognized as a cause of asthma. Positive skin tests and serum IgE antibodies to B. tropicalis have been reported in asthmatic patients from several areas of the world, including Sao Paulo (Brazil), Hong Kong and Tampa (Florida, USA). Analysis of B. tropicalis extracts showed undetectable levels of the major Group I and Group II Dermatophagoides spp. allergens. Immunoabsorption experiments showed that most of the IgE antibodies to B. tropicalis (approximately 70%) reacted with species specific allergens. Murine monoclonal antibodies to B. tropicalis could present antigens that were recognized by human IgG antibodies. Sensitization to E. maynei has been reported in Europe, North and South America and Australia. Analysis of four different E. maynei extracts by ELISA and RIA showed that E. maynei produces an allergen that is antigenically related to Dermatophagoides Group I allergens. The amino acid sequence of this allergen (Eur m I) has recently been reported. Further identification and purification of B. tropicalis and E. maynei allergens is required to develop specific assays for measuring these allergens in dust samples. This will make it possible to investigate the relationship between exposure to B. tropicalis or E. maynei and the development of sensitization and allergic disease. PMID- 1493743 TI - Epidemiology of dust-mite-related disease. AB - For many years it has been suggested that allergens derived from the house dust mite played a major role in the pathogenesis of asthma, eczema and some cases of allergic rhinitis. Recently, house dust mite allergens have been purified and specific immunoassays developed with which exposure to house dust mites and their allergens can be more easily determined. Using these tools, epidemiological studies have provided confirmatory evidence that not only is house dust mite exposure associated with the majority of cases of asthma in children and young adults, but that it is causally related to the development of asthma. PMID- 1493744 TI - Water balance and humidity requirements of house dust mites. AB - The house dust mites, Dermatophagoides farinae, D. pteronyssinus and Euroglyphus maynei, are prevalent in homes in humid geographical areas throughout the world. These mites thrive in humid environments in human dwellings where there is no liquid water to drink. However, their bodies contain 70-75% water by weight, which must be maintained in order to reproduce. Their primary source of water is water vapor which is actively extracted from unsaturated air. At relative humidities above 65-70%, adequate amounts of water can be extracted from unsaturated air to compensate for that lost by all avenues. Active uptake is associated with ingestion of a hyperosmotic solution which is secreted by the supracoxal glands. Active mites do not survive longer than 6-11 days at RHs < or = 50%. They survive extended dry periods by forming a desiccation-resistant protonymphal stage which can survive for months at RHs below the critical humidity for active stages. Feeding rate and allergen production is directly influenced by RH. Mites feed, multiply, and produce more fecal matter at higher RHs than at lower ones. PMID- 1493745 TI - Molecular polymorphisms of house dust mite allergens. AB - Previous studies from this laboratory have described the primary amino acid sequences of the group I and group II allergens from Dermatophagoides pteronyssinus and D. farinae. This report concentrates on polymorphisms of allergens within a species. Firstly, four cDNA clones of Der fII produced by polymerase chain reaction have been sequenced and are compared to the sequences published previously by ourselves and others. Although the sequences come from different sources, Australia and Japan, the overriding conclusion is one of similarity, with only two possible non-conservative changes in the six sequences. The nucleotides were also very conserved including the 3' untranslated regions, although some non-coding differences could be found which may provide a genetic marker. Experiments are reported to help define the group III D. pteronyssinus allergens. Previous studies have characterised the group III of D. farinae as a Mr 29-kDa molecule which can be defined by monoclonal antibodies. A Mr 17-kDa molecule of D. pteronyssinus has been reported with an almost identical N terminal sequence. Here it is described that Der fIII isolated from different preparations of spent mite media by affinity chromatography have predominantly Mr 32-, 28- and 21-kDa forms which vary in degree from batch to batch. 83% of adults and 38% of children react with the preparation by radioimmune dot-blot. The difference between the children and adults is statistically significant and reactivity can be to at least the 32- and 28-kDa form. Antisera produced in mice against the Der fIII react to D. pteronyssinus mite extract by Western blotting primarily to a 32-kDa moiety, but also 28- and 21-kDa forms in some extracts. PMID- 1493747 TI - How relevant are house dust mite-fungal interactions in laboratory culture to the natural dust system? AB - Both house dust and house dust mites Dermatophagoides pteronyssinus contained a wider range of fungi than laboratory mite cultures. In total, nine species of fungi were isolated from D. pteronyssinus in house dust, and these included three xerophilic species (Eurotium amstelodami, Aspergillus penicillioides and Wallemia sebi) commonly found in laboratory cultures of D. pteronyssinus. It is concluded that mites do interact with a similar range of fungi in natural dust and in laboratory culture, but that the diversity of fungal species in the laboratory is reduced and the density of individual fungal species in culture exceeds that of house dust. In a second experiment, dust samples were incubated at room temperature with 75% relative humidity. The diversity of fungi invariably declined from up to 13 genera to the few species recorded in laboratory culture. This suggests that the dominance of xerophilic fungi in laboratory mite rearings is mediated primarily by low relative humidity, and the exclusion of air-borne spores. PMID- 1493746 TI - Allergen exposure and control. AB - Allergens produced by the house dust mites (family Pyroglyphidae) are probably the single most important allergens associated with asthma world wide. If exposure to these allergens in houses could be sufficiently reduced, then asthma symptoms may be markedly reduced and even prevented from being initiated. Only about half of the many attempts to reduce mite allergens in houses have shown any clinical benefit. One reason may be that exposure was not reduced enough--however exposure to mite allergens has never been measured in any trial. This review summarises previous allergen control trials and then provides an outline of allergen exposure, including the nature of exposure, the analytical methods available and the recognised risks of allergen exposure. This provides a perspective to evaluate the individual methods used to kill mites and to reduce exposure to the allergens. The object is to provide a framework to improve and develop allergen avoidance as an effective component of asthma management. PMID- 1493748 TI - The colonisation of new houses by house dust mites (Acari: Pyroglyphidae). AB - House dust mites, Dermatophagoides species (Acari: Pyroglyphidae), produce allergens, known for the provocation of asthma and other allergic reactions. To determine the time needed for complete colonisation of a new house by house dust mites, dust samples were collected from carpets of houses varying from 2 weeks to 2 years in age. In contrast to the expectation, no relation was found between age of the houses on the one hand and average levels of mite-allergens Der pI and Der pII and mite numbers on the other. However, presence of dogs appeared to be positively related to allergen levels. Furthermore, carpets in bedrooms appeared to contain more allergens than carpets in living-rooms. Finally, the age of the mattress was not related to allergen levels of bedroom floors. PMID- 1493750 TI - Socialized medicine in the U.S.A.? PMID- 1493749 TI - Ultrastructure of the reproductive system of the house dust mites Dermatophagoides farinae and D. pteronyssinus (Acari, Pyroglyphidae) with remarks on spermatogenesis and oogenesis. AB - Several parts of the reproductive system of both sexes of Dermatophagoides farinae and D. pteronyssinus are investigated and compared by light-, scanning electron-, and transmission electron microscopy. New techniques have been employed for scanning of the internal structures of these mites. The male reproductive system consists of unpaired testis, paired vasa deferentia, an accessory gland, ejaculatory duct, and copulatory organ. The female reproductive system consists of bursa copulatrix, ductus bursae, receptaculum seminis, paired ducti receptaculi, ovaries, oviducts, one chorion gland, ovipositor, and oviporus. Testis as well as ovaries are characterized by syncytia of nutritional function. The specifics of spermatogenesis are discussed in connection with sperm transfer. Similarities between the construction of the ovaries and oogenesis in astigmatic mites and telotrophic meroistic ovaries in insects are discussed. PMID- 1493751 TI - Cat-scratch disease diagnosis and treatment. PMID- 1493752 TI - Pediatric ear surgery. Part I: The external and middle ears. PMID- 1493753 TI - Pediatric ear surgery. Part II: The inner ear. PMID- 1493754 TI - New directions in early intervention: P.L. 99-457. AB - In conclusion, P.L. 99-457 has important implications for professionals who serve hearing-impaired infants and toddlers. The law challenges traditional, child focused intervention models, and requires professionals to develop programs that are responsive to families' needs. Professionals will need to become familiar with family systems theories, useful family assessment tools, and strategies for collaborative service delivery. Professionals are challenged to determine how enabling relationships can be built with family members. Empowerment of the family system could have far-reaching, positive consequences for the hearing impaired child. PMID- 1493755 TI - Perilymphatic fistula. PMID- 1493756 TI - Cerebrospinal fluid rhinorrhea. PMID- 1493757 TI - Spontaneous retraction pockets in chronic otitis media medical and surgical therapy. AB - Results of a series of 228 spontaneous retraction pockets in chronic otitis media are reported and a classification is proposed. Under medical therapy, 78 retraction pockets of stage I and II (out of 95) were followed for five years. Sixteen percent deteriorated into stage III and were operated on; the others stabilized or improved towards normal tympanic membrane (23%). Different methods of surgical therapy were used in 150 retraction pockets (all the stages III and many stages II). Even with silastic sheeting and strengthening of the tympanic membrane, a recurrent retraction pocket was observed in 24 cases (16%). Functional results were obviously better when the ossicular chain was rebuilt from an intact malleus to an intact stapes and either from an intact malleus to a mobile footplate or from the tympanic membrane to an intact stapes. Surgery of retraction pockets must be used not only to prevent cholesteatoma formation but also to prevent erosion of the stapes. PMID- 1493758 TI - The rotary door flap a breakthrough in laryngotracheal reconstruction. AB - The sternohyoid myocutaneous vascularized flap--the Rotary Door Flap (RDF),--is optimally oriented to serve in laryngotracheal reconstruction. It provides immediate highly vascularized lining and structural support to the augmented airway. Therefore it is one of the most versatile alternative methods available for surgical reconstruction of the stenosed larynx and trachea. This technique has been applied in 46 patients, of whom 14 were in the pediatric group. The features of the flap and the surgical technique are described. PMID- 1493759 TI - Transcanal tympanoplasty: dura versus temporalis fascia. PMID- 1493760 TI - Laser surgery of the larynx: the case for caution. AB - Laser surgery has been advocated for treatment of many laryngeal lesions. Although the CO2 laser has many advantages, its safe use requires special education of the surgeon and operating room team, and considerable surgical skill. Several dangers inherent in laser use for laryngeal surgery must be considered. These include vocal fold scarring secondary to thermal injury, loss of histopathologically important tissue through vaporization, airway fire and others. Laser-related complications must be considered whenever use of this instrument is contemplated. PMID- 1493761 TI - Orbital impalement by a gearshift knob: case report. AB - Penetrating trauma to the orbit may cause complex injuries involving the bone, globe, and brain. Successful treatment requires a strategic scheme for preoperative assessment and management and a multidisciplinary surgical approach. These principles are demonstrated by report of a motor vehicle accident in which the driver sustained orbital impalement by a gearshift knob. PMID- 1493762 TI - Frontal sinusitis with chronic epidural abscess: a case presentation. AB - The incidence of intracranial complications from acute frontal sinusitis has decreased with improved antimicrobial and surgical therapy. However, the physician must maintain a keen awareness and thoroughly investigate any possible signs of intracranial spread. This article discusses a case in which a chronic epidural abscess developed after inadequate therapy was rendered. It also reviews the presentation of and the factors leading to the development of intracranial complications. The treatment required is to eradicate the disease present and prevent future sinusitis. PMID- 1493763 TI - Estimation of hepatic hematopoiesis in second and third trimester singleton gestations using flow cytometric light scatter analysis of archival autopsy tissue. AB - The purpose of this investigation was to develop a simple, quantitative, reproducible and objective method for estimating fetal hepatic hematopoiesis using flow cytometric light scatter measurements and to use this methodology to determine standard values for singleton gestations. Percent hepatic hematopoiesis was estimated from autopsy tissue both flow cytometrically using forward angle and side light scatter characteristics and histologically (single observer) in 67 s and third trimester singleton gestations without evidence of infection, congenital malformation, chronic maternal or placental disorders, or growth retardation. Correlation of flow cytometric and histologic estimates was 0.70 with flow cytometric estimates showing less variability than histologic estimates, especially during the second trimester. Flow cytometric estimates of hepatic hematopoiesis were relatively constant at 50-70% between 16 and 27 weeks gestational age and decreased during the third trimester to a level of approximately 25-30% at term. These results confirm and quantitate the predicted decrease in hepatic hematopoiesis between the second and third trimesters of gestation as well as its persistence at term. In addition, they demonstrate that flow cytometric light scatter analysis is an objective, valid and simple method for estimating hepatic hematopoiesis in archival autopsy tissue and provides objective standard values for comparison with estimates in pathologic gestations. PMID- 1493764 TI - A 1-year follow-up of low birth weight infants with and without bronchopulmonary dysplasia: health, growth, clinical lung disease, cardiovascular and neurological sequelae. AB - A cohort of 86 low birth weight (LBW infants (< 1751 g) including 23 subjects with bronchopulmonary dysplasia (BPD) and 23 matched controls without BPD were checked up at corrected ages of 1, 2, 4, 6, 8 and 12 months. Thirty-six of the subjects were re-hospitalized, mostly because of infections, there being no significant difference in the number of hospitalizations between BPD cases and their controls. Delayed growth was frequent, but a catch-up growth was seen. Eighteen of the subjects (5 with BPD and 7 of controls) were of height below 2 SD at a corrected age of 12 months. Twenty-four (14 with BPD and 3 controls) had persistent respiratory symptoms during the follow-up period and 4 of the BPD subjects still had such symptoms at the age of 1 year. Hoarseness was more frequent in BPD cases than in the controls (8/1 cases). One subject with BPD had transient symptoms of cor pulmonale and 1 without BPD developed transient systemic hypertension. Nine subjects (4 with BPD and 2 controls) had a diagnosis of cerebral palsy at the age of 1 year. PMID- 1493765 TI - Current concepts in retinopathy of prematurity. AB - Significant advances regarding understanding the etiology and treatment of retinopathy of prematurity have occurred in the 50 years since its discovery. Nevertheless, there is still a great deal to be learned. In spite of major technological advances in neonatal care, retinopathy of prematurity is a multi factorial disease and probably cannot be completely prevented. Early intervention in the diagnosis and management of these infants has greatly improved their visual prognosis. Further studies may help pediatricians and neonatologists to understand and control associated risk factors. Ophthalmologists must continue to examine these patients early and follow them closely to control the associated treatable aspects of the disease, such as strabismus and amblyopia. PMID- 1493766 TI - Judging fetal growth from body proportions at birth. AB - Fetal growth velocity from 27 weeks until birth was calculated in 378 infants born after high risk pregnancies from at least three ultrasound measurements of estimated fetal weight and the weight at birth. Anthropometric measurements at birth (weight, head circumference, length, ponderal index and skinfolds), after correction for differences in gestational age, were significantly related to fetal growth velocity. The relation between fetal growth velocity and ponderal index was significant (correlation coefficient = 0.34, P < 0.001). However, the correlations between fetal growth velocity and each of the anthropometric measures disappeared when birth weight relative to gestational age was accounted for. This means that given the birth weight and the gestational age of a newborn infant, body proportions, e.g. ponderal index or skinfold thickness, do not contribute further to the judgment about fetal growth rate. PMID- 1493767 TI - The epidemiological characteristics of unexplained antepartum stillbirths. AB - All antepartum stillbirths weighing 1000 g or more born in Western Australia from 1980 to 1983 were categorised as 'unexplained' or 'explained' based on information from Perinatal Death Certificates. Using data from hospital and doctors' antenatal records a number of variables in each stillbirth category were compared by unconditional logistic regression. Significant differences were observed between the two groups in medical disorders and abnormalities of pregnancy, thus confirming our classification system. Compared with mothers of 'explained' antepartum stillbirths, mothers of unexplained antepartum stillbirths tended to have younger ages at delivery and had associated lower parity, more antenatal visits to the medical practitioner, fewer hospital admissions, a greater chance of having received care by a general practitioner than by a specialist obstetrician and were of more advanced gestation at the time of diagnosis. The results of this study indicate that the epidemiological characteristics of pregnancies resulting in unexplained antepartum stillbirths differ from those resulting in explained antepartum stillbirths. This suggests that unexplained antepartum stillbirths are not merely the result of inadequate obstetrical management but consist of a series of fetal disease states which are not currently amenable to detection. PMID- 1493768 TI - Comparison of enteral and intramuscular vitamin A supplementation in preterm infants. AB - Vitamin A deficiency associated with preterm delivery is not readily reversible using the recommended supplement of 1500 IU per day. It has been reported that 2000 IU of intramuscular vitamin A administered on alternate days for 28 days will correct the deficiency. The objective of this study was to compare this regime with the practice in our nursery of giving 5000 IU of vitamin A per day with the early introduction of feeds. The vitamin A status of ten preterm infants (mean gestation 30.5 weeks) who received intramuscular vitamin supplementation was compared with that of nine infants (mean gestation 30.7 weeks) given enteral vitamin A. Vitamin A status was evaluated on the 32nd day of life using plasma retinol and retinol-binding protein (RBP) concentrations and a modified relative dose response (RDR) test. Plasma retinol and RBP concentrations were similar in the two groups shortly after birth revealing vitamin A deficiency. By the 32nd day of life, plasma retinol and RBP concentrations had risen significantly in both groups and in 70% the modified RDR was normal. Differences between the groups were not observed irrespective of the method of vitamin A administration. None of the infants developed clinical or biochemical vitamin A toxicity. In most preterm infants who tolerate feeds, vitamin A deficiency can be corrected safely by supplementing the feeds with 5000 IU of vitamin A per day. PMID- 1493769 TI - The effects of hypoxanthine, xanthine oxidase and hyperoxia on the accumulation of bilirubin and albumin in young rat brain. AB - Hyperoxia has been suggested as a risk factor for kernicterus. The toxicity of hyperoxia may be mediated by free radicals. We investigated the effects of free radicals, formed by the hypoxanthine/xanthine oxidase system, with and without additional hyperoxia, on the accumulation of bilirubin and albumin in rat brain. Hypoxanthine was infused for 60 min into retrograde carotid catheters in awake, young, male SPRD rats. After 30 min the infusion was briefly interrupted to inject xanthine oxidase 1 U/kg through the same catheter. Group I (controls) received 0.9% NaCl in lieu of hypoxanthine/xanthine oxidase. Groups I and II breathed room air at all times, while group III breathed 90% O2. After 60 min all groups received a bolus dose of 125I-albumin through a peripheral venous catheter, followed by bilirubin 25 mg/kg for 5 min, then bilirubin 35 mg/kg for 55 min. There were no significant differences between the groups as regards serum bilirubin, serum albumin, brain bilirubin, or brain albumin. Neither during normoxic nor hyperoxic conditions did the hypoxanthine/xanthine oxidase system increase the accumulation of bilirubin or albumin in rat brain. PMID- 1493770 TI - The relationship between heart rate and eye movement in the human fetus at 38-40 weeks of gestation. AB - The purpose of this study was to compare two different methods for assessing fetal heart rate (FHR)--fetal eye movement (FEM) synchronization: (1) periods of high (HV) and low (LV) variability in the FHR and the presence (EM) and absence (NEM) of FEM were determined by visual inspection and the degree of association between FHR and FEM was assessed in terms of the fraction of study time for which no periods of LV-NEM and HV-EM could be identified; and (2) the maximum cross correlation coefficient (rmax) and the lag at rmax (Lmax) were determined by direct computer analysis of FHR and FEM data for each fetus. Twenty normal human fetuses between 38 and 40 weeks of gestation were examined for a total of 2051 min (mean 103 min, range 72-150 min). In general, the state HV-EM was observed approximately twice as often as was the state LV-NEM; neither of these two states could be identified during 12.4% of the study time. The coefficient rmax was calculated assuming a sliding 3-min moving window, using either the average FHR (mean 0.53, range 0.31-0.85) or the variability in the FHR (mean 0.52, range 0.18 0.77). No relationship was found between rmax and Lmax calculated using the mean FHR and the fraction of time for which no state could be identified (P = 0.995). When the cross-correlation analysis was performed using FHR variability, a statistically significant relationship was found between the periods of no coincidence (of states LV-NEM and HV-EM) and rmax and Lmax (r2 = 0.32; P = 0.04).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1493771 TI - A possible collicular component of the auditory evoked potential and its relationship to brainstem and cerebellar auditory potentials. AB - Auditory evoked potentials were recorded from the rat using skull screw electrodes inserted over the inferior colliculus and the cerebellum. In addition, brainstem auditory evoked potentials (BAEPs) were also recorded. The response recorded from over the inferior colliculus consisted of a slow positive potential with one of two possible peak latencies. The mean latency of the earlier potential was 5.6 ms and that of the later potential was 6.4 ms. A hypothetical generator for the first collicular potential is the termination of the lateral lemniscus in the ventrolateral inferior colliculus, while the later collicular potential could have its origins within the brachium of the inferior colliculus. None of the principal nor minor BAEP waves corresponded to either of the collicular responses. Nor did the trough of negativity between BAEP waves IV and V which is often thought to reflect activity generated within the midbrain. The potential recorded over the cerebellum also consisted of a slow positivity but with a slightly sharper contour than that of the collicular response. The mean latency of the cerebellar potential was 4.9 ms. As there was no temporal relationship between collicular and cerebellar potentials, the present study provided no support for the theory that cerebellar auditory potentials are artefactual and simply far field reflections of activity generated in the inferior colliculus. Judging by the timing of the BAEP waves, it is also concluded that the afferent volley most likely projects to the cerebellum via a collateral pathway branching off the caudal part of the lateral lemniscus. PMID- 1493772 TI - Electromyographic recording of the jaw reflex in Friedreich ataxia. AB - Jaw jerk was studied in 10 subjects with Friedreich ataxia, and 10 normal subjects for comparison. Electromyographic recording from the right masseter muscle showed a reflex response in all cases, in contrast to the absence of tendon reflexes in the four limbs for the ataxics. The mean latency of the jaw jerk was normal. These observations indicate that the jaw reflex arc is preserved, and that no damage to the trigeminal neuromuscular pathway exists for all the patients observed. PMID- 1493773 TI - Stretch reflex of quadriceps femoris in normal man: methodological considerations and normative data. AB - Short- and long-latency responses to stretching have been evoked in various muscles in the healthy subject. The quadriceps femoris, however, has never been investigated in this connection, despite its functional importance. We studied its stretch reflex in 17 healthy subjects with a torque motor to determine its morphological features in relation to the level of background EMG activity, the stretching velocity and duration and the instructions given to the subject. Two bursts of EMG activity were constantly evoked when the muscle was voluntarily activated. Response magnitude was proportional to the background activity and displacement velocity. Short stretching evoked only one EMG burst. These findings are similar to those from other muscles. Intra-individual variability was evaluated repeating the experiment in the same session without changing position of the electrodes, and then after two months. The long-latency response showed a good intra-individual reproducibility. PMID- 1493774 TI - Changes in P300 latency and amplitude in schizophrenic patients and healthy controls during the examination. AB - In 30 schizophrenic patients (sixteen of the paranoid subtype, 14 of the nonparanoid) and healthy controls (n = 30) event-related potentials were obtained with a somatosensory reaction-time (RT) version of the "oddball paradigm" by stimulating the right (first run) and the left (second run) median nerve. Variations of P300 amplitude and latency and of RT within the average (30 trials) were studied by fractionating off-line the original averages in three subaverages. After stimulation of the right median nerve oscillations on P300 amplitude and latency were observed. After stimulation of the left median nerve there was a trend toward a decrease of the P300 amplitude that reached significance at the electrode P3 for patients (p = 0.014) and at the electrode P4 for controls (p = 0.025). The P300 latency showed variations for patients and controls. The mean-RT was prolonged across the subaverages only for schizophrenics, reaching significance after stimulation of the right median nerve. Paranoid and nonparanoid schizophrenic patients showed similar results on P300 and RT parameters across the subaverages. These results are discussed in terms of the influence of motivation and task involvement on the P300 amplitude. These could be unspecific factors that account for the habituation of the P300 along the examination. PMID- 1493775 TI - Functional relationship between brain regions in schizophrenia evaluated with Pearson's correlation between event-related potentials. AB - As part of a study of the somatosensory P300 event-related potential (ERP) in paranoid and nonparanoid schizophrenic patients (8) Pearson's product-moment correlations between ERP waveforms were calculated to study the functional relationship between brain areas. ERP were recorded from F3, F4, P3 and P4; interhemispheric (F3 to F4; P3 to P4) and intrahemispheric (F3 to P3; F4 to P4) correlations were obtained. There was no significant difference among the paranoid and nonparanoid patients and healthy controls for both the interhemispheric and the intrahemispheric correlations. The lack of disruption of functional relationship between brain areas on the patients do not support the hypofrontality and the laterality hypothesis of schizophrenia. However, the use of neuroleptics by the patients, the study of the whole waveforms and not parts of them and the use of linked-ears reference could account for these negative results. PMID- 1493776 TI - The relation between motor evoked potential and clinical motor status in stroke patients. AB - Forty-one stroke patients and 41 normal controls of matched age, sex and body height were studied by magnetic stimulation of the motor cortex and lower cervical area. The cortical and cervical motor evoked potentials (MEPs) were detected from the abductor pollicis brevis muscle. The amplitudes and latencies of cortical MEPs, central conduction time (CCT), and interside difference of bilateral CCT (DCCT) in stroke patients showed significant difference in comparison with normal controls. The degree of motor weakness was statistically correlated with the severity of cortical MEP findings, but not with the deep tendon reflex and Babinski sign. The abnormal rate of cortical MEP was higher in patients with hemorrhage than in those with infarction. Six out of 17 patients with hemorrhage had prolonged CCT or DCCT, but only 3 out of 24 patients with infarction had the same findings. The cortical MEP findings in putaminal hemorrhage were more severe than in thalamic hemorrhage. In instances of infarction involving total middle cerebral artery territory (cortical and subcortical areas), the cortical MEP was absent in all cases (4/4). It was concluded that cortical MEP findings in stroke patients examined by magnetic stimulation showed good correlation both with the lesion radiologically and the motor deficit clinically. This is an acceptable method for quantitative evaluation of motor system function in stroke. PMID- 1493777 TI - Flexor reflex for assessment of common interneurone activity in spasticity. AB - The purpose of this investigation was to evaluate the alterations of flexor reflex parameters in spasticity and the possibilities to take advantage of them as a method for assessment of common interneurone activity. Clinical and electromyographical examinations were performed on 120 patients with spastic hemiparesis after stroke. The flexor reflex was obtained after supramaximal electrostimulation of the tibial nerve behind the ankle. The stimulus consisted of 50 msec train of 1 msec duration pulses given at 100 Hz. The reflex activity was recorded from the tibialis anterior muscle. As all patients were with hemiparesis the healthy side was used as a control. The patients were subdivided into four groups, each treated with different myorelaxants (Baclofen, Sirdalud, Myolastan and electroacupuncture). After about 25 days treatment the clinical and electromyographic examinations were repeated. The flexor reflex was recorded with two clearly distinguishable responses on the healthy, as well as on the spastic side. On the spastic side a reflex with prolonged latencies and durations, as well as with decreased amplitudes and thresholds of both reflex responses was found. On the spastic side the first reflex response had higher threshold than the second one, while on the healthy side it was vice versa. Moderate correlations were found between most of the reflex parameters. No correlations were found between the reflex parameters and the degree of spasticity. Only after Baclofen treatment all reflex parameters tended to normalized. After treatment with Myolastan, Sirdalud and electroacupuncture only the second response's duration shortened. In conclusion the flexor reflex is a sensitive method for assessment of altered common interneurone activity in spasticity.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1493778 TI - F-wave elicited during voluntary contraction as a monitor of upper motor neuron disorder. AB - Since electrophysiological techniques for assessment of upper motor neuron disorders have yet to be standardized, the potential of employing F-waves to monitor this condition was examined. Subjects were 32 normal adults, 54 patients with upper motor neuron disorder and 20 patients with lower motor neuron disorder. F-waves were recorded from the abductor digiti minimi muscle at rest and under weak voluntary contraction. F-wave amplitudes expressed as a percentage of maximum M-wave were 1.98 +/- 0.83% at rest and 3.73 +/- 1.25% during voluntary contraction in normal group, compared to 3.69 +/- 1.81% and 3.62 +/- 1.68% in the upper motor neuron disorder group, 2.08 +/- 1.45% and 3.52 +/- 1.83% in the lower motor neuron disorder group, respectively. Analysing individual data, 69% of patients with upper motor neuron disorder showed an F-wave at rest within normal limits (+/- 2.5 standard deviation from normal). Voluntary muscle contraction enlarged the F-wave amplitude in normal subjects and patients with lower motor neuron disorder, but the facilitation did not occur in patients with upper motor neuron disorder. Combining F-wave amplitudes at rest and during voluntary contraction revealed differences between the upper motor neuron disorder group and the normal and lower motor neuron disorder groups. It was therefore concluded that F-waves can be used as a monitor of upper motor neuron disorder. PMID- 1493779 TI - Passive long-latency event-related potentials in mental retardation. AB - Long-latency auditory event-related potentials (ERPs) were passively recorded in ten mental retardates and ten age-matched normal controls. Patients were mildly to moderately retarded and had epilepsy controlled with monotherapy, ERPs were recorded from CA-A1+A2, with 1000 and 3000 Hz tones in an "oddball" paradigm. Latency and amplitude of N1, N2, P2, and P3 components were compared in controls and retardates. All ten patients had reproducible AEPs, but these were attenuated in amplitude in four, although amplitudes did not differ significantly from controls. P3 was prolonged in latency in four patients, but patients and controls did not differ significantly. AEP latency and amplitude was not correlated with degree of retardation. These findings suggest that "cognitive" evoked potentials an be recorded passively in persons with impaired cognition, but are not correlated with intellectual ability and may not reflect specific cognitive functions. PMID- 1493780 TI - Reinforcing and punishing consequences of kindling. AB - The motivational consequences of kindling were examined in the conditioned place preference paradigm. In a distinctive environment, rats received stimulation of the amygdala that triggered afterdischarge (AD) alone or AD and generalized seizures. After 4 conditioning trials, preference for the conditioning environment or a control environment was measured. Amygdaloid ADs associated with nonconvulsive seizures (stage 0) produced a conditioned decrease in time spent in the initially preferred chamber by rats receiving stimulation there, and they produced a conditioned increase in time spent in the initially nonpreferred chamber by rats receiving stimulation there. These effects were not large, in that there was no overall mean shift from preference to avoidance, or vice versa; but they were reliable and significant. Similarly, stage 5 seizures produced a small and nonsignificant decrease in time spent in the conditioning chamber in which seizures were triggered. It appears that amygdaloid AD produces weak effects that are either reinforcing or punishing, depending on the behavioral baseline, and that generalized amygdaloid seizures are, at most, mildly punishing. PMID- 1493781 TI - Effects of valproate and E-2-en-valproate on functional and morphological parameters of rat liver. I. Biochemical, histopathological and pharmacokinetic studies. AB - E-2-en-Valproate (E-2-en-VPA; trans-2-en-VPA) and VPA were studied for potential hepatotoxicity in young male Sprague-Dawley rats. Both drugs were administered daily at 750 mg/kg i.p. (divided into three doses a day) for 7 consecutive days. Clinical chemistry parameters were studied before and after the period of treatment. Furthermore, the drug pharmacokinetics and metabolism were analyzed at onset and end of the prolonged administration. Treatment with VPA induced hyperammonemia and other alterations in liver function tests which were not observed after treatment with E-2-en-VPA, although plasma levels of both drugs were comparable. The pharmacokinetics of VPA and E-2-en-VPA in young rats were similar, but analysis of metabolites by gas chromatography-mass spectrometry indicated marked differences in the metabolite profile, e.g., a lack of the suspected hepatotoxic metabolite 4-en-VPA in plasma of rats treated with E-2-en VPA. Histopathological examination of liver sections showed that VPA and E-2-en VPA did not induce degenerative liver lesions or significant alterations in hepatic content and distribution of lipids and glycogen at the doses administered. Only one of the VPA treated rats showed fatty infiltration (microvesicular steatosis). The data demonstrate that, although E-2-en-VPA is more potent than VPA as an anticonvulsant in rats, it does not exert more potent hepatotoxic effects and does not alter ammonia metabolism. Thus the data substantiate previous experimental studies that E-2-en-VPA might be a valuable substitute for VPA. PMID- 1493782 TI - Lack of changes in seizure susceptibility during the estrous cycle in kindled rats. AB - The threshold and pattern of focal and generalized seizures in fully kindled rats during the estrous cycle were investigated. Two groups of rats were studied; one was kindled from stimulation of the basolateral amygdala, the other from stimulation of the anterior portion of the posterior piriform cortex. Determinations of the threshold for focal afterdischarges were either carried out in the morning (between 8 and 9 a.m.) or in the afternoon (between 2 and 3 p.m.). In all experiments, stable and reproducible afterdischarge thresholds were obtained during the different stages of the estrous cycle. The only significant alteration was a reduced seizure duration during metestrus and/or the first day of diestrus in amygdala kindled rats. The data indicate that the natural changes in sex hormone levels during the estrous cycle in rats do not affect seizure susceptibility, at least in the kindling model of epilepsy. PMID- 1493783 TI - Influence of electrical stimulus parameters on afterdischarge thresholds in the rat hippocampus. AB - The influence of electrical stimulus parameters on focal seizure production was studied. Stimulations and recordings were carried out with bipolar electrodes stereotactically positioned in the ventral hippocampus of kindled rats. After discharge thresholds were determined for stimulus trains with different combinations of train durations (0.5, 1, 2, 5, 10 s), intratrain frequencies (10, 20, 50, 60, 100 Hz), and pulse widths (0.5 and 1.0 ms). For a given combination of pulse width and intratrain frequency, thresholds decreased as train duration increased; the effect was profound with shorter durations but markedly attenuated with train durations > or = 5 s. For a particular train duration and pulse width, thresholds varied inversely with intratrain frequency; the degree of variation in the thresholds with frequency was greater the shorter the train. For the train durations studied, thresholds were lower with 1.0-ms pulses for intratrain frequencies > or = 20 Hz. However, for 10 Hz, the 0.5-ms pulses were more effective for 2-, 5- and 10-s trains. After discharge thresholds were found to also vary with the number of pulses in the stimulus trains. For stimuli with fewer pulses, thresholds were higher and showed marked variation with train duration, intratrain frequency, and pulse width. For stimuli with more pulses, thresholds fell to a lower limit and the influence of train duration was substantially lessened. This study provides a systematic examination of the influence of stimulus parameters on generation of focal seizures and should prove useful in designing and interpreting future experiments studying the neurobiology of seizures in the hippocampus and related structures and helpful in antiepileptic drug testing. PMID- 1493784 TI - Intravenous valproate: onset and duration of anticonvulsant activity against a series of electroconvulsions in comparison with diazepam and phenytoin. AB - A series of 5 generalized tonic-clonic seizures within 30 min was induced by repeated transauricular electrical stimulation in mice. In this model, the anticonvulsant potency of intravenous valproate was compared with diazepam and phenytoin. All 3 drugs proved capable of rapidly suppressing the seizures after intravenous bolus injection. Potent anticonvulsant activity of diazepam and valproate was already obtained after 30 s, while phenytoin's onset of action was somewhat slower. In contrast to diazepam, valproate and phenytoin suppressed the seizures at non-sedative doses. ED50s for blockade of generalized tonic-clonic seizures throughout the 30-min period of repeated electrical stimulation were 6.6 mg/kg for diazepam, 28 mg/kg for phenytoin and 212 mg/kg for valproate. Determination of valproate in plasma and brain demonstrated that the rapid onset of anticonvulsant action after intravenous bolus injection was related to rapid drug penetration into brain tissue. The data indicate that an intravenous formulation of valproate might be a useful alternative to phenytoin as a non sedative anticonvulsant for diazepam-resistant status epilepticus. PMID- 1493785 TI - Kainic acid-induced thalamic seizure in cats--a possible model of petit mal seizure. AB - Bipolar depth electrodes were implanted stereotaxically in the thalamus, hippocampus and midbrain reticular formation of cats. Cortical screw electrodes were placed over the bilateral sensorimotor cortex. A guide cannula with an inner injection cannula was inserted unilaterally into the posterolateral ventral nuclei (VPL) of the thalamus. Eight days after the procedures, kainic acid (2.0 micrograms) was injected unilaterally into the VPL via the injection cannula in freely moving animals and electro-clinical observations were made. About 1 h after the kainic acid injection, multiple spikes were observed in the VPL (injection site), which propagated to the subcortical structures. These seizures finally propagated bilaterally to the cortex about 2 h after the injection. About 3-4 h after the injection, small spike and wave complexes repeatedly appeared for a short period of time in cortical leads and cats exhibited behavioral arrest with unresponsiveness during the seizures. About 24 h after the injection, generalized small spike and wave complexes were observed intermittently in cortical and subcortical structures. They persisted for 4-5 s and were associated with behavioral arrest and staring. The results demonstrate that a unilateral microinjection of kainic acid into VPL induced petit mal-like seizure, and suggest that VPL plays an important role in the generation or transfer of spike and wave complexes. PMID- 1493786 TI - Plasma urea and ammonia in epileptic patients and their relatives. AB - The plasma levels of urea and ammonia were examined in patients with primary generalized epilepsy, patients with partial epilepsy and in the first-degree relatives of these subjects. The results show a significant decrease in plasma urea in both groups of patients and their first-degree relatives as compared to the non-epileptic controls. The plasma ammonia concentrations were significantly higher in both groups of patients and in the relatives of generalized epilepsy patients as compared to the controls. The observed changes in plasma urea and ammonia were found not to be due to the effect of anticonvulsant drugs. The data suggest that a metabolic defect in urea synthesis may constitute one of the genetic components in the multifactorial etiologies of primary generalized and partial epilepsies. PMID- 1493787 TI - Conventional and controlled release valproate in children with epilepsy: a cross over study comparing plasma levels and cognitive performances. AB - We studied plasma levels and behavioural effects of a newly developed controlled release formulation of valproate (VPA-CR) in children with epilepsy. Valproate plasma levels and performances in attention and vigilance tasks were monitored during a 12-h period (daytime), both during monotherapy of conventional valproate (VPA) and 4 weeks after switching to a similar dosage of VPA-CR taken once daily. There was no significant difference between the two formulations with respect to mean diurnal trough and peak valproate plasma levels, and to mean fluctuation. The significantly higher Cmax/Cmin ratio during VPA-CR seems mainly due to low valproate plasma levels early in the morning. Neuropsychological assessment showed no significant differences, either between patients and controls, or within patients and controls when comparing the results obtained on the VPA and VPA-CR day. During both VPA and VPA-CR treatment, no correlation was found between cognitive performance and valproate plasma levels. The advantage of VPA CR is that the once daily regimen may increase compliance and is more convenient for schoolchildren. PMID- 1493788 TI - Light chain ratios and concentrations of serum immunoglobulins in children with epilepsy. AB - Serum immunoglobulin G, A and M concentrations and their respective kappa/lambda (kappa/lambda) light chain ratios were studied in 26 children with epilepsy. Fifteen had cryptogenic West syndrome or Lennox-Gastaut syndrome and 11 had other forms of childhood epilepsy. The results were compared to the data of a reference group of healthy children. The mean serum IgG and IgM concentrations were respectively 2.2 g/l (P = 0.007) and 0.4 g/l (P = 0.016) higher in the 26 children with epilepsy compared to the reference group. The kappa/lambda ratios of total serum immunoglobulins, IgG and IgM were respectively 0.10 (P = 0.057), 0.20 (P = 0.001) and 0.14 (P = 0.005) lower in the children with epilepsy than in the reference group. IgA concentration and IgA kappa/lambda ratio were not affected. There were no significant differences between the kappa/lambda ratios of the West and Lennox-Gastaut epilepsy and the other types of childhood epilepsies. The results are further evidence of reciprocal interaction between the nervous system and the immune system in childhood epilepsy. PMID- 1493789 TI - Structure and function of peroxisomes in the mammalian kidney. PMID- 1493790 TI - Peroxisomes in digestive gland cells of the mussel Mytilus galloprovincialis Lmk. Biochemical, ultrastructural and immunocytochemical characterization. AB - The present study was undertaken because of the paucity of information on peroxisomes in molluscs and the increasing importance of these organisms as sensitive indicators of environmental pollution. Peroxisomes were identified by electron microscopy in all three main cell types of the digestive gland of the bivalve mollusc Mytilus galloprovincialis Lmk. They stained weakly with the alkaline diaminobenzidine reaction but showed distinct immunolabeling with an antibody against mammalian catalase by the postembedding protein A-gold procedure. In addition, mussel digestive gland peroxisomes were isolated by differential and metrizamide-density gradient centrifugation, and a 30-fold enrichment of catalase and a 20-fold enrichment of palmitoyl-CoA oxidase was obtained over the initial homogenate. By Western blotting, isolated peroxisomes crossreacted with antibodies to catalase and, furthermore, specific and prominent labeling of isolated peroxisomes was also demonstrated in thin sections incubated with anti-catalase antibodies. These observations establish that peroxisomes in molluscan digestive gland contain the peroxisomal marker enzymes catalase and acyl-CoA oxidase and that they can be labeled by cytochemical and immunocytochemical techniques. Further studies of alterations of molluscan peroxisomes by environmentally relevant xenobiotics are warranted. PMID- 1493791 TI - Brefeldin A inhibits the formation of constitutive secretory vesicles and immature secretory granules from the trans-Golgi network. AB - The effects of brefeldin A (BFA) on membrane traffic between the trans-Golgi network (TGN) and the plasma membrane were investigated in intact PC12 cells and in a cell-free system derived from PC12 cells. In intact cells, BFA caused a virtually complete block of constitutive secretion, as indicated by the lack of release from, and accumulation in, the cells of a [35S]sulfate-labeled heparan sulfate proteoglycan (hsPG). Pulse-chase experiments with [35S]sulfate followed by subcellular fractionation showed that this block was due to the inhibition of formation of constitutive secretory vesicles (CSVs) from the TGN. BFA did not block the depolarization-induced release of [35S]sulfate-labeled chromogranin B (CgB) and secretogranin II (SgII) from secretory granules formed prior to the addition of the drug, showing that BFA does not block secretory granule fusion with the plasma membrane. The presence of BFA did, however, prevent the appearance of [35S]sulfate-labeled CgB and SgII in secretory granules, indicating that the drug inhibits the formation of secretory granules from the TGN. Evidence for a direct block of vesicle formation by BFA was obtained using a cell-free system derived from [35S]sulfate-labeled PC12 cells. In this system, low concentrations of BFA (5 micrograms/ml) inhibited the formation of the hsPG containing CSVs and that of the SgII-containing secretory granules from the TGN to the same extent (50-60%) as, and in a non-additive manner with, the nonhydrolyzable GTP analogue GTP gamma S. Consistent with the inhibitory effects of BFA on vesicle formation from the TGN, BFA treatment of intact PC12 cells led to the hypersialylation of CgB, which presumably was due to the increased residence time of the protein in the TGN. In conclusion, our data are consistent with, and allow the generalization of, the concept that the BFA-induced block of anterograde membrane traffic results from the inhibition of vesicle formation from a donor compartment. PMID- 1493792 TI - Acidification slows the transport but does not influence the polarity of secretion of gp80 in the polarized epithelial cell MDCK. AB - Madin-Darby canine kidney (MDCK) cells stably transfected with a recombinant chicken lysozyme gene were used to examine the effect of cytoplasmic acidification on the secretion of the endogenous gp80 glycoprotein complex and lysozyme. The effect was examined by pulse-chase and immunofluorescence analysis. If filter-grown monolayers were incubated at pH 5.8 the secretion of gp80 was retarded, and the transport of lysozyme was completely inhibited. The immunofluorescence analysis revealed an enrichment of both proteins in the endoplasmic reticulum. The transport block was reversible for both proteins upon transferring the filter-grown monolayer back into medium at pH 7.4. PMID- 1493793 TI - NSP1 depletion in yeast affects nuclear pore formation and nuclear accumulation. AB - The essential yeast nuclear pore protein NSP1 was placed under the control of the regulatable GAL10 promoter. GAL::NSP1 cells grow normally in galactose medium, but arrest in growth upon glucose-induced repression of the GAL::nsp1 gene. During NSP1 depletion, nuclear accumulation of two reporter proteins Mat alpha 2 lacZ and PHO2-lacZ is inhibited, and the chimeric proteins appear in the cytoplasm of GAL::nsp1 cells. Furthermore, the nuclear pore density decreases within the nuclear membrane during early NSP1 depletion. Upon reinduction of the NSP1 gene after NSP1 depletion, NSP1 is targeted to the nuclear envelope, the nuclear pore density increases, and nuclear accumulation of reporter proteins is restored. PMID- 1493794 TI - Cytochemical characterization of two types of nuclear bodies in Cicer arietinum L. AB - The present study was carried out to characterize two distinct types of nuclear bodies, the nucleolus-associated bodies (NABs) and the satellites (SATs) using some specific staining, enzyme and immunogold labeling techniques in Cicer arietinum L. These bodies are of interest as the functional components of plant nucleus. DNA-specific staining and labeling with anti-DNA, a monoclonal antibody, were employed to verify the presence of DNA in NABs as well as in SATs. The enzyme-gold labeling technique was used to compare the relative amounts of RNase gold and protease-gold labeling over the NABs. In NABs, RNase-gold labeling was relatively low compared to the protease-gold labeling. Ag-NOR staining revealed a similar content of NOR-silver proteins in both NABs and granular zone of the nucleolus. The NABs do not contain any DNA as they show negative response to DNA specific stains and also when incubated with anti-DNA, only few gold particles are found over these structures. The SATs, on the other hand, react positively with DNA-specific stains, and high labeling is recorded with anti-DNA along with the dense chromatin masses. PMID- 1493795 TI - The effects of transforming growth factor-beta and serum on proteoglycan synthesis by tendon fibrocartilage. AB - The effects of transforming growth factor-beta (TGF-beta) and serum on proteoglycan synthesis by tissue explants from the fibrocartilaginous region of adult bovine tendon and by cells in culture from this region were assessed. The most characteristic effect of added TGF-beta on both explant tissue and cells in culture was enhanced synthesis of one small proteoglycan-biglycan. Lowered serum concentration diminished incorporation of Na2 35SO4 into proteoglycans. Added TGF beta (1 ng/ml) stimulated cell proliferation, increased overall proteoglycan synthesis, and increased the length of glycosaminoglycan chains on all secreted proteoglycans. The effect of TGF-beta on cells in culture was highly consistent whereas explants from different animals showed greater variability in the response. It was concluded that TGF-beta did not specifically promote or maintain the cartilaginous nature of this tissue because supplementing medium with TGF beta did not significantly alter the ratio of large/small proteoglycans synthesized by tissue explants. However, the observation of enhanced biglycan synthesis by TGF-beta suggests that TGF-beta could be involved in differentiation of regions of tendon subjected to compression, because compressed tendon contains both decorin and biglycan small proteoglycans whereas tensional tendon contains primarily decorin. Excess decorin added to cell culture medium did not affect the ability of TGF-beta to enhance synthesis of biglycan. PMID- 1493796 TI - Molecular characterization of vascular smooth muscle decorin: deduced core protein structure and regulation of gene expression. AB - Two overlapping clones containing sequences homologous to bovine, human and chicken decorin have been recovered from poly A+ RNA isolated from rat vascular smooth muscle cells (VSMC) using cDNA cloning and reverse transcription polymerase chain reaction (PCR) methodologies. Results of nucleotide sequence analysis performed on these clones demonstrated that they encode the complete mature rat decorin protein expressed by VSMC. Within the coding region, rat decorin exhibits 76% nucleotide sequence homology to human and bovine decorin, and 69% homologous to chicken decorin indicating a significant level of conservation among these species. This level of conservation among species was also maintained at the protein level with rat decorin being 77% homologous to its human, bovine and chicken homologues. As previously observed its human homologue, rat decorin, is made up of seven, tandem, leucine-rich repeat sequences. Furthermore, within the core of these repeats was the consensus protein sequence NKISK which has been proposed to be the fibronectin binding region of decorin (G. Schmidt et al., Biochem. J. 280, 411-414 (1991)). The vast majority of amino acid substitutions within rat decorin were of the conservative type. The highest frequency of amino acid substitutions were found to be localized within a hypervariable region located near the amino terminus of the decorin core protein. Unlike rat biglycan, rat decorin mRNA levels were found to increase significantly in density-arrested VSMC cultures. In contrast to rat biglycan gene expression, no quantitative differences in rat decorin mRNA levels were observed between proliferating VSMC and VSMC made quiescent through serum depletion. Finally, specific extracellular matrix (ECM) proteins were able to regulate the expression of decorin at the mRNA level in a slightly different manner than previously observed for biglycan. PMID- 1493797 TI - Molecular organization and antiproliferative domains of arterial tissue heparan sulfate. AB - Heparan sulfate isolated from mammalian arterial tissue inhibits the growth of homologous arterial smooth muscle cells when added to subconfluent cell cultures at a concentration of 50 to 100 micrograms/ml culture medium. Disintegration of the heparan sulfate molecule by hydrazinolysis that deacetylates N acetylglucosaminyl residues and by subsequent treatment with nitrous acid at pH 3.9 results in the formation of a mixture of oligosaccharides which was further resolved into sulfate-enriched oligosaccharides with antiproliferative activity in an in vitro bioassay system. A decasaccharide and dodeca/tetradecasaccharide fraction had a significantly higher antiproliferative effect on arterial smooth muscle cells than the native heparan sulfate molecule. The antiproliferative oligosaccharides have a sulfate content of 0.9 to 1.2 sulfate groups/disaccharide unit and consist of 60 to 70% monosulfated, disulfated, and trisulfated disaccharide units. Up to 32% of the sulfate groups were in 2-position of the uronic acid. In contrast, nitrous acid degradation of heparan sulfate at pH 1.5, which cleaves glycosidic linkages of N-sulfoglucosaminyl residues, results in the formation of sulfate-poor or sulfate-free oligosaccharides without antiproliferative potency. The results indicate that (a) heparan sulfate has a heterogeneous molecular organization where sulfate-rich domains are separated by sulfate-poor sequences and that (b) the antiproliferative activity of heparan sulfate resides in domains enriched with 2-O-sulfated uronic acid residues. PMID- 1493798 TI - Cell-associated proteoheparan sulfate mediates binding and uptake of thrombospondin in cultured porcine vascular endothelial cells. AB - [125I]Thrombospondin (TSP) binds to porcine endothelial cells in a specific, saturable and time-dependent fashion and is endocytosed by a receptor-mediated process. The N-terminal heparin-binding domain is necessary for the interaction with the cell surface. Binding and uptake is inhibited by heparin and to a much smaller extent by other vascular glycosaminoglycans. Chemical modification of lysine and arginine residues of TSP, but not treatment of the molecule with neuraminidase, resulted in a pronounced loss of binding at the cell surface. Treatment of cells with heparitinase but not with chondroitin ABC lyase caused inhibition of binding and uptake of TSP. Inhibition of sulfation of proteoglycans on the cell surface by chlorate leads to a dose and time-dependent inhibition of binding and degradation of TSP. In the presence of chlorate, newly synthesized TSP is not incorporated into the cell matrix but mainly released into the culture medium, whereas localization and incorporation of newly synthesized fibronectin is not altered. A cell surface proteoheparan sulfate was identified as TSP binding macromolecule by affinity chromatography. The data emphasize the role of heparan sulfate proteoglycan as a receptor-like molecule for the specific interaction with thrombospondin. PMID- 1493799 TI - Tissue-specific expression of type XIV collagen--a member of the FACIT class of collagens. AB - The collagens represent a highly diverse superfamily of extracellular matrix proteins that can be divided into several distinct families. One of the families, called FACIT (fibril-associated collagens with interrupted triple-helices) family, contains molecules that appear to be associated with cross-striated fibrils composed of members of the fibrillar collagen family. We have determined a portion of the primary structure of a recently discovered member of the FACIT family, chicken alpha 1(XIV) collagen, based on cloning and sequencing cDNAs. A synthetic oligopeptide from within the carboxy-terminal non-triple-helical domain of the alpha 1(XIV) chain has been used for generating specific polyclonal antibodies. The antiserum, PS1, recognizes a 220 kDa polypeptide in immunoblots of extracts of chicken skin, tendons, and cartilage. Sequencing of a tryptic peptide generated from purified, immunoreactive material, gives a sequence identical to that derived from cDNA sequencing, providing strong support for the type XIV-specificity of PS1. We have examined the expression of type XIV collagen in developing chick embryos by immunostaining of sections from 12-day-old embryos with PS1 and by Northern blot analysis of RNA from several tissues from both 12- and 17-day-old embryos. The results show that type XIV collagen is prevalent within relatively dense connective tissues such as dermis, tendons, perichondrium, perimysium, the stroma of lungs and liver, and blood vessels. PMID- 1493800 TI - Membrane-associated proteoglycans produced by Sertoli cells are not randomly distributed on the cell surface. AB - Sertoli cells in culture synthesize two membrane-associated proteoglycans (PGs) containing as glycosaminoglycan (GAG) moieties either chondroitin sulfate (CS) or CS and heparan sulfate (HS); the latter PG is, therefore, referred to as the mixed PG. To determine if these PGs are randomly distributed on the cell surface, Sertoli cell monolayers were treated with chondroitinase ABC, and then the remaining PGs were analyzed by DEAE-Sephacel chromatography. The results obtained with Sertoli cell monolayers show that the CS of the mixed PG is degraded by chondroitinase, while the CS-PG is not degraded. In contrast, chondroitinase treatment of Sertoli cells in suspension shows that both the mixed PG and the CS PG are degraded. From this, it is inferred that the mixed PG is apically oriented and the CS-PG is basolaterally oriented. Studies of the adhesion of germ cells to Sertoli cell monolayers give further support to the apical location of the mixed PG and suggest that its HS moiety is involved in the attachment of germ cells to Sertoli cells. PMID- 1493801 TI - Eosinophil cationic protein alters proteoglycan metabolism in human lung fibroblast cultures. AB - Eosinophil cationic protein (ECP), a highly basic protein secreted from eosinophilic granulocytes, has been shown to take part in the inflammatory reaction. The involvement of ECP in fibroblast activation was therefore investigated in cell culture. Production of proteoglycans, hyaluronan and collagen in the presence of ECP was measured after incorporation of radioactive precursors and separation into different proteoglycan classes using gel and ion exchange chromatography and hydrophobic interaction chromatography. Proteoglycan accumulation in the cell layer was increased two- to fivefold at an ECP concentration of 10 micrograms/ml. No effect on collagen, other proteins or hyaluronan was noted. Furthermore, no effect was observed on cell proliferation. The increased proteoglycan accumulation could be inhibited by addition of heparin or of antibodies to ECP. The effect could not be mimicked by the two basic peptides protamine and poly-L-lysine, speaking in favor of specificity. The increase in proteoglycan material was seen exclusively in the intracellular pool. No change of proteoglycans in the medium or the cell surface-associated pool was noted. The increase in the cell layer was accounted for by a two- to fivefold increase in free chains of heparan sulfate and dermatan sulfate. No change was seen in the proteoglycan pattern. No effect on proteoglycan synthesis or on endocytosis was noted. The increased accumulation of polysaccharide was caused by inhibited degradation of glycosaminoglycans. The half-lives of large and small heparan sulfate proteoglycans/glycosaminoglycans and dermatan sulfate proteoglycans/glycosaminoglycans in the cell layer are increased four- to sevenfold. We conclude that ECP inhibits proteoglycan degradation in fibroblasts, which indicates a role for the eosinophil in generation of fibrosis. PMID- 1493802 TI - Chicken gizzard 5'-nucleotidase functions as a binding protein for the laminin/nidogen complex. AB - Soluble and reconstituted 5'-nucleotidase were used in the binding assays to the laminin/nidogen complex. They both are shown to interact specifically and in a saturable manner with the laminin/nidogen complex using a solid-phase binding assay. Dissociation constants in the region of 10(-8) M were determined for the association of soluble and membrane-bound 5'-nucleotidase. Scatchard analysis of the binding data indicate a stoichiometry of about 2.7 of the homodimeric soluble 5'-nucleotidase to the laminin/nidogen complex. The association of 5' nucleotidase with laminin/nidogen occurs in the absence of divalent metal ions and does not require N-linked carbohydrate moieties of both laminin/nidogen and 5'-nucleotidase. 5'-Nucleotidase also associates with isolated laminin although with reduced affinity. No binding to isolated nidogen was observed. Peptides containing the RGD sequence did not influence the binding reaction. Monoclonal and polyclonal antibodies directed against 5'-nucleotidase and laminin specifically perturb the association of the reconstituted enzyme to laminin/nidogen. Sulfated polysaccharides such as heparinsulfate and dermatansulfate modulate the interaction of 5'-nucleotidase and laminin/nidogen in a complex biphasic manner and might also regulate the binding reaction in vivo. Immunohistochemistry shows a close spatial correlation of 5'-nucleotidase and laminin also in the epithelium of the small intestine pointing to an in vivo interaction of both glycoproteins. PMID- 1493803 TI - Detection of binding sites for biotinylated neoglycoproteins and heparin (endogenous lectins) during cerebellar ontogenesis in the rat: an ultrastructural study. AB - In a previous paper (Kuchler et al., Eur. J. Cell Biol. 52, 87-97 (1990)), endogenous carbohydrate-binding sites were studied at the optical level during rat cerebellar development on sections of fixed tissue using synthetic tools, biotinylated neoglycoproteins, in conjunction with subsequent avidin-peroxidase staining. It was shown that these tools were capable of revealing carbohydrate binding sites during development of the rat cerebellum. The staining pattern with the individual probes disclosed variable developmental regulation and consequently suggested that recognition processes during cerebellar development may include several types of carbohydrate determinants. However, studies at the light microscope could not give information on potential membrane-bound localization of carbohydrate-binding sites and therefore discern the possible involvement of these molecules in cell adhesion processes. Furthermore, nuclear staining was suggested at the optical level. In order to elucidate these points, we examined the localization of mannose-, fucose- and heparin-binding sites at the electron microscopic level. Ultrastructural studies demonstrate that these tools are very efficient in detecting intracellular carbohydrate-binding sites, but failed to detect most of them expressed at the cell surface when using immunocytochemical techniques for known receptors, probably because of the interaction of these carbohydrate-binding sites with endogenous membrane-bound ligands. The significance of the nuclear staining and of part of the nucleolus found with fucose-containing neoglycoprotein and of the nuclear staining found with heparin are discussed. PMID- 1493804 TI - Fibronectin shedding by Leishmania may influence the parasite-macrophage interaction. AB - Fibronectin (FN) is a large extracellular matrix protein involved in the endocytosis of several types of particles by different phagocytes. Here we investigated the role of FN in the entry and destruction of Leishmania amazonensis promastigotes (flagellated form) by murine resident peritoneal macrophages. We also studied the lateral mobility of this protein on the surface of the parasite cells using a immunogold technique. We compared the effects of addition and depletion of FN on infective and non-infective populations of Leishmania promastigotes. The invasion by the latter but not by the former, was increased by FN, and the uptake of these cells was more sensitive to FN depletion from the culture medium. We also observed enhanced killing of intracellular infective promastigotes upon FN addition to the macrophage cultures. Immunocytochemical localization of FN on the surface of the flagellates revealed that the parasite cells released bound FN by membrane shedding in a constitutive fashion. Therefore we conclude that FN removal by shedding may be part of a physiological mechanism by which the parasites evade intracellular destruction by host cells. PMID- 1493805 TI - Endocytosed transferrin in African trypanosomes is delivered to lysosomes and may not be recycled. AB - It has been shown in mammalian systems that the passage of transferrin-colloidal gold (Tf-Au) through the endocytic system is influenced by the size of the gold colloid (Neutra, M. R. et al., J. Histochem. Cytochem. 33, 1134-1144 (1985); Woods, J. W. et al., Eur. J. Cell Biol. 50, 132-143 (1989)). However, in both Trypanosoma brucei brucei and Trypanosoma congolense, widely varying sizes of Tf Au (Tf-Au5 and Tf-Au15) have been shown to proceed to lysosomes (Webster, P., Eur. J. Cell Biol. 49, 295-302 (1989); Webster, P., D. Grab, J. Cell Biol. 106, 279-288 (1988)). Using an affinity-purified anti-bovine transferrin IgG we have demonstrated that, in both T. brucei and T. congolense, native transferrin, like Tf-Au, is found in the flagellar pocket, coated vesicles, tubular structures, and lysosome-like organelles where it appears to be concentrated. The presence of Tf in the lysosomes was confirmed in colocalization experiments using T. congolense, where native bovine transferrin colocalized with a trypanosome lysosomal marker, a cysteine protease. The data suggest that, unlike the situation in mammalian cells where most transferrin is recycled to the cell surface, in African trypanosomes transferrin is routed into lysosomes and may not, therefore, be recycled. PMID- 1493806 TI - Microneme secretion in Coccidia: confocal laser scanning and electron microscope study of Sarcocystis muris in cell culture. AB - A monoclonal antibody (mcab) raised against a subcellular fraction of Sarcocystis muris cystozoites was used to localize microneme antigens before, during and after invasion of cultured cells. The mcab recognized a 20 and 22 kDa protein under reducing and non-reducing conditions on Western blots and localized an antigen in cystozoites in the apical part of the parasites. Confocal laser scanning microscopy of invading cystozoites revealed the secretion of a microneme antigen at the apical tip of the parasite. The secreted microneme antigen was attached to the host cell surface at the invasion site and spread along the surface of the infected cells. Electron microscopy using immunogold labeling showed that the microneme antigen was distributed in patches on the surface of infected cells and present on infected cells more than 60 min post-infection. The function of microneme antigens during parasite-host cell interactions is discussed. PMID- 1493807 TI - Functional and structural damage in Leishmania mexicana exposed to the cationic peptide dermaseptin. AB - The effect of dermaseptin (DS), a 34 amino acid residue cationic peptide isolated from Phyllomedusa sauvagii skin, has been studied on promastigotes of Leishmania mexicana growing in vitro. Within 5 min of incubation in the presence of DS, the flagellated parasites lost their motility. DS inhibited promastigote growth by 50% at a concentration of 3 microM and by 100% at 10 microM. Immunocytochemical, freeze fracture, label fracture and electron microscopic observations have shown that the amphipathic peptide generates perturbations of the lipid bilayer leading to altered permeability of the surface membrane and death of the parasite. PMID- 1493808 TI - Distribution of glutamylated alpha and beta-tubulin in mouse tissues using a specific monoclonal antibody, GT335. AB - A monoclonal antibody (GT335) directed against polyglutamylated tubulin was obtained by immunization with a synthetic peptide which mimics the structure of the polyglutamylated site of alpha-tubulin. This peptide corresponds to the C terminal sequence Glu441-Gly448 and was chemically modified by the addition of two glutamyl units at Glu445. The specificity of GT335 was assayed by direct and competitive enzyme-linked immunosorbent assay (ELISA) against tubulin and several synthetic peptides differing either by the structure of the added polyglutamyl chain or by their amino acid sequence. Further characterization was carried out by immunoblotting detection after one- or two-dimensional sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE). The epitope appears to be formed by at least two constituents: a basic motif of monoglutamylation which is retained in the polyglutamylated forms independent of their degree of glutamylation, and some elements of the polypeptide chain close to the site of glutamylation. Given the specificity of GT335 and the delineation of its epitope, our results indicate that, in addition to alpha and beta' (class III)-tubulin, other beta-tubulin isotypes are also glutamylated. This antibody has been used to analyze the cell and tissue distributions of glutamylated tubulin. In mouse brain extracts, GT335 reacts strongly with alpha-tubulin and, to a lesser extent, with beta' (class III) and beta-tubulin. The same reactivity is also observed with cultured neurons whereas astroglial cells exhibit only low levels of glutamylated tubulin. In non-nervous mouse tissues such as spleen, lung or testis, glutamylation was shown to involve only beta-tubulin, but at far lower levels than in brain. PMID- 1493809 TI - Binding between mammalian spermatid-ectoplasmic specialization complexes and microtubules. AB - Ectoplasmic specializations (ESs) are submembrane specializations that consist of Sertoli cell plasma membrane linked by an ordered array of actin filaments to a cisterna of endoplasmic recticulum (ESER). They are thought to function in the spermatid-Sertoli cell adhesion junction. Microtubules occur adjacent to the cytoplasmic face of the ESER and are oriented parallel to the long axis of the Sertoli cell, the direction of spermatid translocation during spermatogenesis. Our hypothesis that spermatid orientation and translocation in the seminiferous epithelium is microtubule dependent predicts that microtubules bind to ESs. To test for binding between microtubules and ESs, we have developed an in vitro assay in which spermatid-ES complexes were isolated from the seminiferous epithelium and incubated with bovine brain microtubules that were labeled with [3H]GTP and stabilized with taxol. Binding was determined by scintillation counts from gradient fractions enriched for spermatid-ES complexes and depleted of unbound microtubules by differential centrifugation. Our data indicate that microtubules bind to spermatid-ES complexes in a substrate concentration dependent manner and can be released with 5 mM GTP or 10 mM MgATP. Binding is competitively reduced with excess unlabeled microtubules and is inhibited by 100 microM vanadate and 2 mM N-ethylmaleimide (NEM). The amount of binding is unchanged by 10 microM vanadate, 2 mM erythro-(2-hydroxy-3-nonyl)adenine (EHNA) or 1 mM 5'-adenylylimidodiphosphate (AMP-PNP). Immunofluorescence and autoradiographic data confirm that labeled microtubules bind to ES locations on spermatid-ES complexes. These data are consistent with the hypothesis that spermatid translocation is a microtubule-based transport event. PMID- 1493811 TI - Interleukin-1 from baboon peripheral blood monocytes: altered response to endotoxin (lipopolysaccharide) and Staphylococcus aureus stimulation compared with human monocytes. AB - The baboon Papio ursinus does not elicit a febrile response upon injection with endotoxin, but fever is produced when injected with Staphylococcus aureus particles (Zurowsky, Y., H. Laburn, D. Mitchell, Can. J. Physiol. Pharmacol. 65, 1402-1407 (1987)). We address the question whether baboon peripheral blood monocytes produce interleukin-1 (IL-1) when stimulated with endotoxin or S. aureus particles in culture. Results show that little IL-1 biological activity was produced from endotoxin-stimulated baboon peripheral blood monocytes, compared with S. aureus-stimulated cells. Measurements of IL-1 beta by radioimmunoassay supported these data. This is contrary to data from human monocytes, which show greater sensitivity to endotoxin. Examination of IL-1 beta mRNA from endotoxin-stimulated and S. aureus-stimulated baboon monocytes, however, showed that more mRNA for IL-1 beta was present in endotoxin-stimulated monocytes than in cells stimulated with S. aureus. This illustrates the possibility that the production and/or the secretion of IL-1 beta is not as efficient in baboon monocytes as it is in human monocytes. PMID- 1493810 TI - Interleukin-1 is a motility factor for human breast carcinoma cells in vitro: additive effect with interleukin-6. AB - Interleukin-1 beta (Il-1 beta) and interleukin-1 alpha (Il-1 alpha) were shown to act as motility factors for the human breast carcinoma cell lines SK-BR-3 and ZR 75-1 in vitro. Both cytokines induced transition from the stationary to the motile phenotype (spreading). Il-1 beta stimulated translocation, shape change and random migration (chemokinesis) of SK-BR-3 cells as demonstrated by time lapse video recordings and by a modified Boyden chamber assay. Interleukin-6 (Il 6) stimulated spreading of the SK-BR-3 cells; an additive effect with Il-1 beta on spreading and fast plasma membrane movements was evidenced. In the SK-BR-3 cell line, the signal transduction of Il-1 beta and Il-6 differed, since only the effect of Il-6 on spreading was sensitive to pertussis toxin. Both Il-1 beta and Il-6 required protein synthesis to stimulate spreading, since cycloheximide inhibited the effect of the cytokines. Induction of an autocrine loop of Il-6 in the SK-BR-3 cells by Il-1 beta was unlikely, since after stimulation with Il-1 beta, no induction of Il-6 activity was measured, nor was inhibition of stimulated spreading seen in the presence of an antiserum against Il-6. Addition of Il-8 or of an antiserum against Il-8 did not affect spreading. We concluded that Il-1 and Il-6 could act as motility factors for human breast carcinoma cells, in both an independent and an additive way.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1493812 TI - Introduction and summary of principal conclusions to the first European workshop in aviation cardiology. PMID- 1493813 TI - The European aeronautical environment. PMID- 1493814 TI - Cardiomyopathy and aircrew fitness. PMID- 1493815 TI - Adult congenital heart disease with special reference to the data on long-term follow-up of patients surviving to adulthood with or without surgical correction. PMID- 1493816 TI - Mitral leaflet prolapse: aspects of fitness to fly. PMID- 1493817 TI - Medical-cause accidents in commercial aviation. PMID- 1493818 TI - Sino-atrial node dysfunction, atrioventricular block and intraventricular conduction disturbances. PMID- 1493819 TI - Implications of lone atrial fibrillation/flutter in the context of cardiovascular fitness to fly. PMID- 1493820 TI - Aviation and antiarrhythmic medication. PMID- 1493821 TI - Ventricular pre-excitation and professional aircrew licensing. PMID- 1493822 TI - Cardiovascular risk and risk factors in the context of aircrew certification. PMID- 1493823 TI - Cardiac pacing and aviation. AB - Certain applicants with stable disturbances of rhythm or conduction requiring cardiac pacing, in whom no other disqualifying condition is present, may be considered fit for medical certification restricted to multi-crew operations. The reliability of modern pacing systems appears adequate to permit restricted certification even in pacemaker dependent subjects except for certain models of pacemakers and leads known to be at increased risk of failure. These are to be avoided. There is little evidence to suggest that newer devices are any more reliable than their predecessors. Single and dual chamber systems appear to have similar reliability up to 4 years, after which time significant attrition of dual chamber devices occurs, principally due to battery depletion. All devices require increased scrutiny as they approach their end of life as predicted from longevity data and pacing characteristics. Unipolar and bipolar leads are of similar reliability, apart from a number of specific bipolar polyurethane leads which have been identified. Atrial leads, particularly those without active fixation, are less secure than ventricular leads and applicants who are dependent on atrial sensing or pacing should be denied certification. Bipolar leads are to be preferred due to the lower risk of myopotential and exogenous EMI. Sensor-driven adaptive-rate pacing systems using active sensors may have reduced longevity and require close scrutiny. Activity-sensing devices using piezoelectric crystal sensors may be subject to significant rate rises in rotary wing aircraft. The impracticality of restricted certification in helicopters will, in any event, preclude certification. Such devices would best be avoided in hovercraft (air cushioned vehicle) pilots. Only minor rate rises are likely in fixed-wing aircraft which are unlikely to be of significance. Anti-tachycardia devices and implanted defibrillators are inconsistent with any form of certification to fly. PMID- 1493824 TI - Cardiological aspects of aviation safety--the new European perspective. PMID- 1493825 TI - Epidemiology of hypertension in Europe. PMID- 1493826 TI - Definitions of hypertension in relation to risk; the role of ambulatory monitoring. PMID- 1493827 TI - Hypertension and the probability of an incapacitating event over a defined period: impact of treatment. AB - (1) The risks of coronary heart disease, cerebrovascular disease and all-cause mortality associated with increasing levels of pressure are graded and continuous from the lowest to the highest levels. (2) Data from several large prospective studies allow evaluation of individual risk based on blood pressure level but may require modification in the context of aircrew. (3) Because cardiovascular risk factors appear to interact and 'cluster' in hypertensives, a broadened approach to the evaluation of risk for the individual and the management of hypertension is necessary and appropriate. (4) Anti-hypertensive treatment has been shown in trials to reduce the incidence of stroke but appears much less effective at reducing coronary events. It may be that a management policy which involves an assessment of and intervention on all risk factors together, incorporating the use of anti-hypertensive drugs which do not have adverse metabolic effects will be more effective in this context. Evaluation of such a policy in a long-term morbidity and mortality trial is however urgently required. PMID- 1493828 TI - Strategies for the management of hypertension in aircrew. PMID- 1493829 TI - Lipid screening in aircrew: pros and cons. PMID- 1493830 TI - Coronary artery disease: a European perspective. PMID- 1493831 TI - What is the predictive value of exercise electrocardiography in the investigation of male aircrew aged 40-60 years old? PMID- 1493832 TI - The natural history of angiographically demonstrated coronary artery disease. PMID- 1493833 TI - Coronary angioplasty--long-term follow-up results and detection of restenosis: guidelines for aviation cardiology. A European view. PMID- 1493834 TI - Late results following coronary artery bypass grafting. AB - Coronary bypass surgery is well into its third decade. The randomized trials of saphenous vein grafting together with the various registries[57-60] have provided us with a wealth of information not only on the effects of surgery but also on the natural history of coronary heart disease itself. Numerous improvements have been introduced, the most notable being the use of the IMA as an arterial conduit. Thus the results of the randomized trials which significantly influence our clinical decisions may not accurately reflect what modern surgery can now offer, especially to the type of patient being operated upon in the 1970s. Nevertheless the decision about whom to operate on probably will not change, at least in terms of clinical variables affected by the coronary anatomy and left ventricular function. But there is every expectation that the long-term clinical results of surgery will be better since graft patency has already been shown to have improved as a result of anti-platelet therapy and, most of all, by the IMA. We will never have a randomized trial to prove this, but experience to date justifies this conclusion. The other great change that has occurred during the last decade is angioplasty and hopefully the randomized trials will put this technique in perspective. But practice has already changed and surgery for single vessel disease is now much less commonly performed given the greater appreciation of the good prognosis with which this lesion is associated and the ease with which angioplasty can alleviate the symptoms it causes.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1493835 TI - Relationship of left ventricular hypertrophy to risk of cardiovascular events, and its relevance to medical certification of aircrew. PMID- 1493836 TI - The relevance of residence time theory to pharmacokinetics. PMID- 1493837 TI - Effect of penicillin on the clinical course of streptococcal pharyngitis in general practice. AB - The aim of the study was to explore whether penicillin was superior to placebo in altering the clinical course of proven streptococcal pharyngitis. A randomised, parallel, double blind placebo controlled trial of 10 days duration was undertaken in 42 general practices in the Gent region (Flemish part of Belgium). Phenoxymethylpenicillin (adults 250 mg t.i.d. and children 125 mg t.i.d.) or placebo were administrated to 173 patients, aged 5 to 50 y, with acute sore throat and a positive culture for Group A beta-haemolytic streptococci. Penicillin and placebo tablets were identical. Patient compliance was monitored by assay of penicillin in urine (Sarcina lutea method). The primary outcome variable was sore throat as recorded by the physician on Day 3. The experiences of the patients themselves over the 10 day period were also assessed. Secondary outcome variables were other local and general symptoms and signs of streptococcal throat infection. In the penicillin group on Day 3, 23.2% of the patients still complained of sore throat versus 65.9% in the placebo group: difference 42.7% (C.I. 29.4%, 56.1%). This finding was confirmed by survival analysis of the symptom 'sore throat', as recorded by the patients. The physicians recorded on Day 3 a significant positive effect on another symptom (malaise: P < 0.04) and certain clinical signs (abnormal throat: P < 0.07; and redness of throat: P < 0.003). Penicillin had more adverse effects than placebo (P < 0.007). It also inhibited the rise in ASLO (P < 0.001). In this study in general practice, penicillin had a slight but definitive positive effect on the clinical evolution of streptococcal pharyngitis.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1493838 TI - 24-hour anti-ischaemic action with once daily nifedipine. Experience obtained with a fatty-alcohol matrix tablet in patients with coronary artery disease. AB - The ability of a fatty-alcohol matrix, slow-release tablet of nifedipine 60 mg to maintain a 24-hour anti-ischaemic action in the fixed dose of 60 mg once daily has been investigated in a randomised, placebo-controlled, double-blind trial. 12 normotensive patients with angiographically proven coronary artery disease (stenosis of at least one major vessel > or = 70%) were studied. The anti ischaemic response was assessed over a period of 4 days as changes in the exercise-induced ST-segment depression 6 h and 24 h post-dose, and ST-segment changes in 24-h ambulatory ECGs. A measurable anti-ischaemic response was observed in 8 of the 12 patients. Exercise-induced ST-segment depression 6 h after the administration of nifedipine was reduced by 30% compared to placebo, and there was still a measurable anti-ischaemic response 24-h post-dosing. Both responses were independent of changes in exercise blood pressure. In 7 patients with ischaemic episodes in the 24-h ECGs, nifedipine treatment had only a minor effect on the intensity and duration of ischaemia. It is concluded that a significant anti-ischaemic effect lasting 24 h could be demonstrated using effort induced ST-segment changes in patients with angiographically proven coronary heart disease, who were treated once daily with nifedipine 60 mg as a fatty alcohol slow release tablet. PMID- 1493839 TI - Salmeterol protects against hyperventilation-induced bronchoconstriction over 12 hours. AB - To study the dose-response relationship of salmeterol for protection against a naturally occurring stimulus, isocapnic hyperventilation tests of cold air were done in 16 asthmatic patients. The subjects inhaled either 50 micrograms salmeterol, salbutamol 200 micrograms, or placebo in a double-blind, randomised, cross-over study. The FEV1 was measured prior to medication and the provocative ventilation (PV20) required to induce a 20% fall in FEV1 was calculated by linear interpolation from ventilation-response curves obtained 0.5, 4, 8, and 12 h after medication. Following salbutamol, the mean FEV1 were 4.11, 3.89, 3.58, and 3.55 l, with a significant difference from placebo up to 4 h. Following salmeterol, mean FEV1 values were 3.95, 4.10, 3.93, and 3.88 l, with a significant difference from placebo up to 12 h. The mean PV20FEV1 after salbutamol was 78.8, 58.5, 52.7, and 48.4 l.min-1, the 0.5 h value being significantly different from placebo. After salmeterol, the mean PV20FEV1 values were 84.6, 82.5, 67.8, and 65.8 l.min 1, with a significant difference from placebo up to 12 h. We conclude that, besides its long-lasting bronchodilating effect, salmeterol protects against hyperventilation-induced bronchoconstriction for at least 12 h. PMID- 1493840 TI - The effects of acute and repeated doses of zolpidem on subjective sleep, psychomotor performance and cognitive function in elderly volunteers. AB - We gave 24 healthy elderly volunteers with a perceived sleep onset of at least 30 minutes zolpidem 5 mg, zolpidem 10 mg, or placebo for 7 days in a double-blind, three-way, crossover study. The morning after nocturnal dosing, psychomotor performance and cognitive ability were measured using tests which are sensitive to the residual effects of hypnotics and to the effects of drugs on various indicators of sleep quality. The tests were: Choice Reaction Time; Tracking; Critical Flicker Fusion Threshold; Memory Scanning; Word Recognition; the Leeds Sleep Evaluation Questionnaire and Line Analogue Rating Scales. Zolpidem produced a subjective improvement in sleep but did not impair performance the following day. Furthermore, during repeated administration, there was no tolerance to the effects of sleep latency and quality of sleep, nor adverse effects on task performance. PMID- 1493841 TI - The effects of temazepam and ethanol on human psychomotor performance. AB - We have studied the effects of temazepam, alone and in combination with ethanol, on psychomotor performance in six healthy men and women using a battery of five microcomputer-based tasks before and 30, 90, and 150 min after treatment. The tests were pursuit tracking, divided attention, two four-choice reaction time tests and tapping rate. The entire battery required 25 min. The subjects also reported their mood at each testing time using a computerized bipolar mood scales test. Temazepam (15 mg) plus ethanol (peak blood concentration of 11 mmol.l-1) significantly impaired divided attention, tracking, and reaction time over a 3 h period. There was significant impairment versus placebo for each drug alone on some of the tests. Plasma and urine concentrations of temazepam and temazepam glucuronide were measured, but there was no significant temporal correlation between impairment and drug or metabolite concentration in either plasma or urine. The subjects knew when they had taken ethanol, but could not discriminate temazepam from ethanol whether alone or in combination. The subjects rated their performance similarly after each of the four treatment conditions. The performance on the tracking, divided attention, and PAB reaction time tasks used in this study was impaired by a combination of temazepam and ethanol in doses which may not cause impairment when each is given alone. PMID- 1493842 TI - Prevalence of drug-treated diabetes mellitus in Belgium. Results of a study with the collaboration of a network of pharmacies. AB - Within the framework of a European concerted action on diabetes mellitus (EURODIAB SubArea C), an epidemiological study was established in Belgium in 1990 in order to estimate the prevalence of drug-treated diabetes mellitus. An assessment was made of the sales of insulin and oral antidiabetic drugs and the average daily dose used. A sample of people with diabetes, clients of 107 pharmacies, provided the data to establish average daily doses. Those pharmacies, spread over the 9 provinces of the country, represent 2% of all private pharmacies in Belgium. Over a 2 month period each pharmacist presented a questionnaire to each client receiving an antidiabetic drug. In 1990, 164 per 10,000 inhabitants were treated with antidiabetic drugs, which means that there were approximately 163,000 drug-treated diabetics in Belgium. At the time of the survey 65% of the diabetics in the sample were 60 years or older. Overall, 38% of drug-treated diabetics took insulin, and 30% of them took only human insulin. Treatment type varied by the province where the pharmacy was located. The provinces of Hainaut and Luxembourg-Namur had a higher percentage of diabetics on oral treatment. This is the first description in Belgium of the prevalence of drug-treated diabetes and of the pattern of prescribing of these drugs. PMID- 1493843 TI - Acetylator phenotypes of Jordanian diabetics. AB - The acetylator phenotype was determined in 31 insulin-dependent (IDDM) and 110 noninsulin-dependent (NIDDM) Jordanian diabetics, and was compared to that of 160 healthy volunteers of the same ethnic group. Dapsone was used as the test drug. The rapid acetylator phenotype was slightly less frequent in IDDM and slightly more frequent in NIDDM. Neither of the differences was significant. When acetylator status in the two types of diabetes mellitus was compared, there was a significant difference among the two groups. Patients with IDDM had a higher percentage of the slow acetylator phenotype when compared to NIDDM patients. The association between acetylator status and IDDM in Jordanians, which agrees with that reported for the Saudi Arabian population, is the reverse of what is found in European populations. The results demonstrate ethnic differences in acetylator status among IDDM patients. PMID- 1493844 TI - Heating and cooling of the nitroglycerin patch application area modify the plasma level of nitroglycerin. AB - 19 healthy volunteers wore a nitroglycerin patch releasing 10 mg per 24 h for 2 h. Subsequently, the skin area surrounding the patch was exposed to 15 min of local heating with an infrared bulb (Group A, n = 10), or local cooling with an ice-pack (Group B, n = 9). The patch was protected by an insulating shield (Styrofoam). After 10 min of heating, the median (Walsh) plasma nitroglycerin level increased from 3.1 to 7.6 nmol.l-1. Body temperature remained constant. After 15 min of cooling the median plasma level had dropped from 2.1 to 1.4 nmol.l-1. The results demonstrate that changes in skin temperature may cause extensive short-term changes in the bioavailability of nitroglycerin. Presumably, a subcutaneous or cutaneous reservoir builds up during transdermal treatment, and changes in regional cutaneous blood flow affect the rate of drainage from the reservoir into the systemic circulation. PMID- 1493845 TI - The sensitivity of human blood platelets to the aggregating agent ADP during different dietary sodium intakes in healthy men. AB - We have investigated the effect of varying sodium intake on the renin-angiotensin system, ADP-induced platelet aggregation in vitro, and blood 5-HT concentrations in 9 male volunteers. Systolic blood pressure was slightly reduced during a low sodium diet, whereas the diastolic pressure remained unchanged. Plasma renin activity and aldosterone concentration both fell significantly when sodium intake was increased; plasma angiotensin II concentration also fell, but not significantly. There was a significant fall in haematocrit after an increased sodium intake, but there was no change in the whole-blood platelet count after correcting for this. There were no significant changes in either total (i.e. PRP) or platelet 5-HT concentrations. The extent of platelet aggregation induced by 5 and 20 mumol.l-1 of ADP increased significantly when dietary sodium intake was increased. When compared with low or normal sodium intakes, lower concentrations of ADP were required to produce 50% of maximum aggregation after a high sodium intake. The 5-HT2 receptor antagonist ketanserin (1 mumol.l-1 in vitro) reduced the extent of aggregation induced by 5 mumol.l-1 ADP after the volunteers had taken a high sodium diet, whereas the angiotensin II receptor antagonist saralasin (1 nmol.l-1) increased the rate of aggregation after the low sodium diet. Thus, during a high sodium intake, human platelets become more sensitive to the aggregating agent ADP. It is possible that this effect is mediated via platelet 5-HT2 receptors, since ketanserin abolished the increase in salt-induced aggregation seen with 5 mumol.l-1 ADP. PMID- 1493846 TI - Failure of N-acetylcysteine to reduce low-density lipoprotein oxidizability in healthy subjects. AB - We have studied the effects of N-acetylcysteine, which is thought to have antioxidant properties, on the susceptibility of low-density lipoprotein to oxidation and on whole-blood glutathione concentrations in six healthy volunteers. N-acetylcysteine was given orally in a dosage of at 1.2 g per day for 4 weeks, followed by 2.4 g per day for a further two weeks. The susceptibility of low-density lipoprotein to in vitro Cu(2+)-oxidation was determined by continuously measuring the formation of conjugated dienes. Whole-blood concentrations of reduced and oxidized glutathione were also determined. N acetylcysteine had no effect on the susceptibility of LDL to oxidation. Concentrations of vitamin E in the serum and in low-density lipoprotein were not changed. Compared with controls the concentration of glutathione in N acetylcysteine treated subjects was reduced (-48%) and the concentration of oxidized glutathione was higher (+80%). The GSH/GSSG-ratio, a marker of oxidative stress was 83% lower. The results do not support the supposed antioxidative action of N-acetylcysteine. It seems more likely that N-acetylcysteine acts as a pro-oxidant in the dosage used. PMID- 1493847 TI - Influence of oral contraceptive agents on kidney function and protein metabolism. AB - The present study was an investigation of the effect of oral contraceptives on kidney function as well as a brief examination of protein metabolism, since glomerular filtration rate depends to a large extent on daily protein intake. 28 healthy women not taking contraceptives and 46 healthy women (aged 20-28 y) on one of three different types of oral contraceptive (combination preparations) were investigated [Minulet/Femovan, Marvelon, Diane]. In all groups on oral contraceptives the endogenous creatinine clearance was significantly increased. The potassium excretion rate was significantly elevated in the groups taking Marvelon and Diane, and the sodium excretion rate was significantly increased in those on Minulet/Femovan and Diane. In all groups on contraceptives the albumin excretion rate was numerically but not significantly elevated. No significant differences were found in the daily oral protein intake or the nitrogen excretion rate on comparing the groups taking contraceptives with the control group. However, the ratio nitrogen excretion rate/daily protein intake was significantly increased in those on Minulet/Femovan and Diane. The study has shown that besides their various effects on renal tubular function, oral contraceptives are able to increase the glomerular filtration rate, and certain types have a protein catabolic effect. PMID- 1493848 TI - Pharmacokinetics and effects of atrial natriuretic factor during hypothermic cardiopulmonary bypass. AB - The pharmacokinetics of a bolus dose of synthetic atrial natriuretic factor (ANF) 50 micrograms and its effects on urine output, blood pressure and plasma renin activity have been studied in 5 patients undergoing hypothermic cardiopulmonary bypass for cardiac surgery. The half-lives of the fast and slow components were 2.4 min and 14.2 min, respectively. The volume of the central compartment was 16.7 l and the volume of distribution at steady-state was 38.9 l. The total plasma clearance was 3.8 l.min-1. ANF significantly increased urine output and decreased blood pressure, but it did not affect plasma renin activity. PMID- 1493849 TI - Yohimbine pharmacokinetics and interaction with the sympathetic nervous system in normal volunteers. AB - The pharmacokinetics of yohimbine and its effects on sympathoadrenal function were studied in 13 young, healthy, male volunteers after an IV bolus dose of 0.25 or 0.5 mg.kg-1. Pharmacokinetic analysis showed that distribution was rapid, with a half life between 0.4 and 18 min, and the elimination half life ranged between 0.25 and 2.5 h. The volume of distribution (Vss) was 74 l, (range 26 to 127 l). Only 0.5 to 1% of unchanged yohimbine was found in the urine, indicating that the major part of the drug was eliminated by hepatic clearance. Total plasma clearance was 117 l.h-1, which exceeds the hepatic plasma flow. This means that yohimbine is a high extraction drug with considerable extra-hepatic metabolism. Fractional urine sampling revealed that 0.5-1% of unchanged yohimbine was excreted in urine in a biphasic manner. The data also suggested the existence of a slower elimination phase, with a half life of 13 h. The venous plasma concentration of noradrenaline (NA) increased 3-fold within 15 min after the yohimbine injection while plasma adrenaline (A) and neuropeptide Y-like immunoreactivity (NPY-LI) remained unchanged. The plasma concentration-effect relationship of the changes in circulating NA followed counter-clockwise hysteresis. The results show that the hyperadrenergic state elicited by therapeutic doses of the alpha 2-adrenergic autoreceptor antagonist, yohimbine, is due to an interaction with NA but not to release of A or NPY in man. PMID- 1493850 TI - Pharmacokinetics of temocapril hydrochloride, a novel angiotensin converting enzyme inhibitor, in renal insufficiency. AB - The pharmacokinetics of temocapril hydrochloride, a novel prodrug-type angiotensin-I converting enzyme (ACE) inhibitor, has been studied in patients with mild (Group II) to severe (Group III) renal insufficiency in comparison with subjects with normal renal function (Group I). The pharmacokinetic parameters of the active diacid metabolite, including Cmax, AUC and half-life (t1/2), showed only slight changes between the three groups: AUC (0-inaffinity) was significantly larger in Group III than Group I, and t1/2 tended to be prolonged in Group III, but the change was not significant. The urinary recovery of the diacid was significantly decreased in Group III. (Group I, 28.1%, Group II, 21.6%, Group III, 12.8%). Compared with other ACE inhibitors, which are mainly excreted through the kidney, the plasma concentration of the active diacid metabolite was hardly influenced by renal function. It was speculated that lowering of the dose of temocapril might be recommended only in patients with severe renal insufficiency. PMID- 1493851 TI - Single-dose and steady-state pharmacokinetics of sabeluzole in senile dementia of Alzheimer type patients. AB - The single- and repeated-dose pharmacokinetics of sabeluzole have been determined in six elderly patients with [senile] dementia of the Alzheimer type. After a single oral dose of 10 mg sabeluzole, the peak plasma concentration was attained at 1 to 4 h; it averaged 42 ng.ml-1. On repeated dosing (10 mg b.d.), steady state was virtually attained after 3 days of treatment. Steady-state mean trough and peak plasma concentrations fluctuated between 53 and 94 ng.ml-1. The mean terminal half-life after a single dose and at steady-state was of the order of 33 h. Sabeluzole was well tolerated and at the end of treatment, no systematic changes in blood haematology, biochemistry or urinalysis were seen. PMID- 1493852 TI - The pharmacokinetics of the beta 2-adrenoceptor agonist fenoterol in healthy women. AB - We have studied the pharmacokinetics of fenoterol in healthy women during and after a 3 h intravenous infusion of different doses within the therapeutic range for tocolysis (0.5 microgram.min-1, 1.0 micrograms.min-1, and 2.0 micrograms.min 1). A specific and sensitive radioimmunoassay was used for the determination of fenoterol. For compartmental analysis the plasma concentration time data were fitted with the TOPFIT program, assuming two exponentials. The total clearance of fenoterol increased with dose (1299 ml.min-1 at 0.5 microgram.min-1, 1483 ml.min 1 at 1.0 micrograms.min-1, and 1924 ml.min-1 at 2.0 micrograms.min-1), as did the apparent volume of distribution (from 49 l at the lowest to 85 l at the highest dose). In contrast, the apparent half-lives were not dose-dependent, with t1/2.lambda 1 4.8 min and t1/2.lambda z 52 min. PMID- 1493853 TI - Can transforming growth factor beta be useful as a protective agent for pluripotent hematopoietic progenitor cells? PMID- 1493854 TI - TGF-beta 3 protects normal human hematopoietic progenitor cells treated with 4 hydroperoxycyclophosphamide in vitro. AB - In this study we have investigated the ability of transforming growth factor-beta 3 (TGF-beta 3, 1000 pM) to protect hematopoietic bone marrow (BM) progenitor cells from the cytotoxic activity of 4-hydroperoxycyclophosphamide (4-HC, 100 microM) in vitro. Hematopoietic progenitors were purified by negative depletion of accessory and maturing cells or enriched by positive (CD 34+ cells) selection. For comparison the same treatment was tested on three different lymphoid cell lines CEM, SK-DHL-2, and LY-16. The experimental protocol was designed to mimic ex vivo purging conditions. Therefore, tumor cells and enriched hematopoietic precursors were mixed with irradiated BM cells. Our results demonstrated that preincubation of enriched progenitor cells with TGF-beta 3 for up to 72 h followed by 4-HC treatment resulted in an increased survival of colonies derived from granulocyte-macrophage (CFU-GM) and erythroid (BFU-E) colony-forming cells, whereas a substantially lower number of colonies was observed in the control group. Similar results were observed when BM cells were first treated with 4-HC followed by TGF-beta 3 incubation for 24 or 48 h. In contrast, TGF-beta 3 provided no protection to the 4-HC cytotoxicity toward the lymphoma and leukemia cell lines. Three to four log of tumor cell killing was induced by 4-HC in the presence or absence of preincubation with TGF-beta 3. These data suggest that TGF beta 3 is able to protect normal BM progenitors from the cytotoxic activity of an alkylating agent (4-HC) in vitro, whereas it does not offer any protection to lymphoma cell lines. These findings will have important implications for developing better purging conditions for autologous GM transplantation. PMID- 1493855 TI - Hematopoietic growth factors in anemia of Belgrade laboratory (b/b) rats. AB - In this study, the extent to which growth factor production and microenvironment might be responsible for defective erythropoiesis and granulopoiesis in anemic b/b rats is investigated. Radioimmunoassay-determined serum erythropoietin (Epo) levels are high in b/b rats and closely related to degree of anemia. The low number of erythroid progenitors in b/b rats despite a high Epo level suggested that the defective erythropoiesis could be due to a low level of burst-promoting activity (BPA). A pokeweed mitogen-stimulated medium (PWM-SCM) was prepared with b/b rat spleen cells and used in normal and anemic rat bone marrow and spleen cultures to determine BPA and other growth factor levels. No erythroid burst forming unit-derived colonies were found but granulocyte-macrophage colony forming units were counted in significant number, suggesting that the production of growth factors that supports the growth of granulopoietic progenitors is not significantly disturbed. Because BPA is produced mainly by T-lymphocytes, the low BPA level in b/b rat PWM-SCM raised the question of the functional capacity of T lymphocytes. Investigations showed a decrease in the proliferative activity of b/b rat spleen mitogen-activated T-lymphocytes to about 20% of controls as well as a decrease in interleukin-2 activity in b/b rat spleen cell supernatants. These results point to defective T-lymphocytes. A study of bone marrow fibroblastoid cell colonies (CFU-F) revealed significantly lower CFU-F counts in the b/b rats. This finding is indicative of a disturbed microenvironment, which could also to some extent be responsible for decreased growth factor production and depressed hematopoiesis in the b/b rat. PMID- 1493857 TI - Pluripotent hematopoietic stem cells of low and high density can repopulate W/Wv mice. AB - We have studied several features of pluripotent hematopoietic stem cells (PHSC) and day-12 spleen colony-forming units (CFU-S12) in murine bone marrow. C57BL/6J marrow cell suspensions were separated by elutriation and fractions were obtained at flow rates (FR) of 25 ml/min, 29/30 ml/min, 35 ml/min, and with the rotor off. All four fractions contained PHSC that could repopulate W/Wv mice, but significant numbers of CFU-S12 were found only in the three higher FR fractions. Cells in the FR29/30 fraction were shown to have almost three-fold more repopulating activity than fresh marrow in a competitive repopulation assay. The PHSC in fractions separated by elutriation were enriched by depleting cells expressing specific lineage markers with monoclonal antibodies and magnetic immunobeads. As few as 10(4) lineage negative (lin-) cells from FR35 or 10(5) lin -cells from FR25 conferred long-term multilineage repopulation in W/Wv mice, as demonstrated by Southern blot analysis of DNA from recipient thymus and bone marrow. We conclude that PHSC are heterogeneous for cell size and density and that the highest concentration of PHSC resides in the subset of intermediate density present in the FR29/30 fraction. PMID- 1493856 TI - Synthesis and deposition of glycosaminoglycans in the murine hemopoietic stromal line S17: modulators of the hemopoietic microenvironment. AB - The murine hemopoietic stromal cell line S17 can support either myelopoiesis or lymphopoiesis depending on the culture conditions (i.e., the presence of steroid or mercaptoethanol). The glycosaminoglycans are important components of the extracellular matrix, which influence hemopoietic cell proliferation. Accordingly, glycosaminoglycans have been compared under different growth conditions. Under myeloid conditions (with steroid) a higher proportion of the sulfated glycosaminoglycans was incorporated into the cell layer and the extracellular matrix was increased, whereas synthesis was reduced under lymphoid conditions (with mercaptoethanol). The inclusion of steroid or mercaptoethanol did not alter the nature of the heparan sulfate synthesized as shown by DEAE anion-exchange chromatography, cleavage with specific enzymes and resolution of the digestion products by gel electrophoresis (oligomapping), and glycosaminoglycan size. The major species of sulfated proteoglycan synthesized under the different growth conditions (200 and 110 kd for the culture supernatant and 110, 71, and 38 kd for the cell layer) were shown to be very similar by polyacrylamide gel electrophoresis. Although no qualitative difference was found biochemically between the major glycosaminoglycans/proteoglycans, scanning electron microscopy revealed major differences in the pattern of deposition of the glycosaminoglycans. Under myeloid conditions, a rich fibrous matrix covered the cell layer, whereas under lymphoid conditions glycosaminoglycan was sparsely deposited. The arrangement of the extracellular matrix may have important consequences for myelo- and lymphopoiesis. PMID- 1493858 TI - Constitutive expression of a megakaryocytic functional property by murine erythroleukemia (Friend) cells: the incorporation of serotonin. AB - Murine Friend-derived erythroleukemia cells (MEL) are generally believed to be unipotential progenitors inducible to terminal erythroid differentiation. However, we found that MEL can constitutively incorporate significant amounts of radiolabeled serotonin ([3H]5-HT). Because this process is typical of cells belonging to the megakaryocytic lineage, we investigated the significance and mechanisms of 5-HT incorporation in the MEL system. We observed that: 1) normal murine erythroid cells and erythroid progenitors do not incorporate [3H]5-HT, as well as normal murine myeloid cells and the human myeloid cell line HL-60; on the other hand, the human erythroleukemia cell lines K562 and HEL, which have been shown to constitutively express megakaryocytic features, were able to incorporate [3H]5-HT; 2) MEL incorporated 5-HT by an active and saturable mechanism, dependent on temperature and sodium concentration in the medium; and 3) 5-HT uptake was very rapid. Moreover, because about 65% of cell-associated radioactivity was no longer displaced by the cold substrate, we assumed it to represent "true" cytoplasmic internalization. Finally, 5-HT incorporation by MEL was inhibited by clomipramine, ouabain, and reserpine, which are known inhibitors of 5-HT uptake in platelets. The commitment of MEL to terminal erythroid differentiation by hexamethylene bisacetamide or dimethyl sulfoxide greatly reduced the capacity to incorporate [3H]5-HT. These results seem to suggest that the MEL system, although mainly erythroid as regards its differentiation capability, constitutively expresses features of the megakaryocytic lineage, possibly disclosed by the ability to incorporate 5-HT. This hypothesis was further supported by the findings that 30%-40% of uninduced MEL were labeled by a polyclonal antibody raised against murine platelets that selectively recognized megakaryocytes in murine bone marrow smears. PMID- 1493859 TI - The effect of AS101 on the reconstitution of T-cell reactivity following irradiation or cyclophosphamide treatment. AB - AS101 (ammonium trichloro[dioxyethylene-O-O']tellurate) is a new synthetic compound previously described by us as having immunomodulating properties and minimal toxicity. Phase II clinical trials are currently in progress with AS101 on cancer patients. AS101 has been recently found to have both radioprotective and chemoprotective effects on hemopoiesis of irradiated mice or mice treated with cyclophosphamide (CYP). In this study the effect of AS101 on the recovery of the immune system from sublethal irradiation or CYP treatment was assessed. Mice were injected once with AS101 24 h before being irradiated with 450 cGy or treated with 250 mg/kg body weight CYP. At various time points after treatment the functional capacity of the immune system was determined. It was found that AS101 could significantly reduce the decrease in the number of spleen cells and thymocytes, the decrease in the proliferation rate of these cells to the T-cell mitogen concanavalin A, and the decrease of interleukin 2 secretion by spleen cells. AS101 could initially protect these functions because they were increased over control levels immediately 24 h after treatment. AS101 was also shown to normalize the distribution of T-cell subsets that was impaired following both treatments. These results suggest an immunoregulatory role for AS101 in counteracting chemotherapy and radiation-induced immunological suppression as well as its usefulness as an adjunct treatment of cancer when used in combination with CYP or irradiation. PMID- 1493860 TI - Trigeminal excitation of dorsal neck motoneurones in the cat. AB - Excitation of dorsal neck motoneurones evoked by electrical stimulation of primary trigeminal afferents in the Gasserian ganglion has been investigated with intracellular recording from alpha-motoneurones in the cat. Single stimulation in the Gasserian ganglion ipsi- and contralateral to the recording side evoked excitatory postsynaptic potentials (EPSPs) in motoneurones innervating the lateral head flexor muscle splenius (SPL) and the head elevator muscles biventer cervicis and complexus (BCC). The gasserian EPSPs were composed of early and late components which gave the EPSPs a hump-like shape. A short train of stimuli, consisting of two to three volleys, evoked temporal facilitation of both the early and late EPSP components. The latencies of the gasserian EPSPs ranged from 1.6 to 3.6 ms in SPL motoneurones and from 1.6 to 5.8 ms among BCC motoneurones. A rather similar latency distribution between 1.6 and 2.4 ms was found for ipsi- and contralateral EPSPs in SPL and BCC motoneurones, which is compatible with a minimal disynaptic linkage between primary trigeminal afferents and neck motoneurones. Systematic transections of the ipsi- and contralateral trigeminal tracts were performed in the brain stem between 3 and 12 mm rostral to the level of obex. The results demonstrate that both the ipsi- and contralateral disynaptic and late gasserian EPSPs can be mediated via trigeminospinal neurones which take their origin in the nucleus trigeminalis spinalis oralis. Transection of the midline showed that the contralateral trigeminospinal neurones cross in the brain stem. Systematic tracking in and around the ipsilateral trigeminal nuclei demonstrated that the axons of ipsilateral trigeminospinal neurones descend just medial to and/or in the medial part of the nucleus. Spinal cord lesions revealed a location of the axons of the ipsilateral trigeminospinal neurones in the lateral and ventral funiculi. Interaction between the ipsi- and contralateral gasserian EPSPs showed complete summation of the disynaptic EPSP component, while the late components were occluded by about 45%. These results show that the disynaptic EPSPs are mediated by separate trigeminospinal neurones from the ipsi- and contralateral side, while about half of the late EPSPs are mediated by common neurones which receive strong bilateral excitation from commissural neurones in the trigeminal nuclei. Spatial facilitation was found in the late gasserian EPSP but not in the disynaptic gasserian EPSP by conditioning stimulation of cortico- and tectofugal fibres. Disynaptic pyramidal and tectal EPSPs, which are mediated by reticulospinal neurones, were facilitated by a single stimulation in the gasserian ganglion at an optimal interval of 2 ms.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1493861 TI - Anatomical pathways from the optic tectum to the spinal cord subserving orienting movements in the barn owl. AB - Electrical stimulation of the optic tectum in many vertebrate species elicits eye, head or body orienting movements in the direction of the receptive field location recorded at the site of stimulation; in the barn owl, tectal stimulation produces short latency saccadic head movements (du Lac and Knudsen 1990). However, the barn owl, like other avians, lacks a direct projection from the tectum to the spinal cord, implying that less direct connections underlie tectally mediated head movements. In order to determine the pathways by which the tectum gains access to spinal cord circuitry, we searched for overlap regions between tectal efferent projections and the locations of cells afferent to the spinal cord. Tectal efferent pathways and terminal fields were revealed by anterograde labeling using horseradish peroxidase (HRP) or tritiated amino acids injected into the optic tectum. Cells afferent to the spinal cord were identified by means of retrograde labeling using HRP, rhodamine, or rhodamine-coupled latex beads injected into the cervical spinal cord. A comparison of results from the anterograde and retrograde labeling experiments demonstrated several areas of overlap. All of the cell groups that both received heavy tectal input and contained a high proportion of cells projecting to the spinal cord were located in the medial half of the midbrain and rhombencephalic tegmentum, and included the red nucleus, the interstitial nucleus of Cajal, the medial reticular formation, the nucleus reticularis pontis giganto-cellularis, and the nucleus reticularis pontis oralis. All of these cell groups receive their tectal input from the medial efferent pathway, one of three major output pathways from the tectum. The other two output pathways (the rostral and the caudal) project to regions containing no more than a few scattered cells that are afferent to the spinal cord. Based on these data and on the functions of homologous cell groups in other vertebrates, we hypothesize that the medial efferent pathway and its brainstem target nuclei are primarily responsible for tectally mediated orienting head movements in the barn owl. PMID- 1493862 TI - Neural basis for eye velocity generation in the vestibular nuclei of alert monkeys during off-vertical axis rotation. AB - Activity of "vestibular only" (VO) and "vestibular plus saccade" (VPS) units was recorded in the rostral part of the medial vestibular nucleus and caudal part of the superior vestibular nucleus of alert rhesus monkeys. By estimating the "null axes" of recorded units (n = 79), the optimal plane of activation was approximately the mean plane of reciprocal semicircular canals, i.e., lateral canals, left anterior-right posterior (LARP) canals or right anterior-left posterior (RALP) canals. All units were excited by rotation in a direction that excited a corresponding ipsilateral semicircular canal. Thus, they all displayed a "type I" response. With the animal upright, there were rapid changes in firing rates of both VO and VPS units in response to steps of angular velocity about a vertical axis. The units were bidirectionally activated during vestibular nystagmus (VN), horizontal optokinetic nystagmus (OKN), optokinetic after nystagmus (OKAN) and off-vertical axis rotation (OVAR). The rising and falling time constants of the responses to rotation indicated that they were closely linked to velocity storage. There were differences between VPS and VO neurons in that activity of VO units followed the expected time course in response to a stimulus even during periods of drowsiness, when eye velocity was reduced. Firing rates of VPS units, on the other hand, were significantly reduced in the drowsy state. Lateral canal-related units had average firing rates that were linearly related to the bias or steady state level of horizontal eye velocity during OVAR over a range of +/- 60 deg/s. These units could be further divided into two classes according to whether they were modulated during OVAR. Non-modulated units (n = 5) were VO types and all modulated units (n = 5) were VPS types. There was no significant difference between the bias level sensitivities relative to eye velocity of the units with and without modulation (P > 0.05). The modulated units had no sustained change in firing rate in response to static head tilts and their phases relative to head position varied from unit to unit. The phase did not appear to be linked to the modulation of horizontal eye velocity during OVAR. The sensitivities of unit activity to eye velocity were similar during all stimulus modalities despite the different gains of eye velocity vs stimulus velocity during VN, OKN and OVAR. Therefore, VO and VPS units are likely to carry an eye velocity signal related to velocity storage.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1493863 TI - Effect of corticotectal tract lesions on relative motion selectivity in the monkey superior colliculus. AB - Many cells in the superficial layers of the monkey superior colliculus are sensitive to the relative motion between a small target moving through the classic receptive field and a textured, moving background pattern that fills the visual field beyond the classic receptive field. The cells respond well when motion of the target differs from that of the background, but their responses are suppressed when the target moves in phase with the background. To determine whether this relative motion sensitivity depends on input to the colliculus from visual cortex, we studied colliculus cells in immobilized, anesthetized monkeys after unilateral thermocoagulation, or anesthetic blockade, of the corticotectal tract at the level of the pulvinar. In the colliculus ipsilateral to the corticotectal tract lesions, relative motion sensitivity was significantly reduced when compared either with the colliculus in intact animals or with the colliculus contralateral to the lesion. However, a moving-background stimulus still had a modest suppressive effect compared with a stationary background ("background motion sensitivity"), as is the case for intact animals. Anesthetic blockade of the corticotectal tract had similar effects; relative motion sensitivity, but not background motion sensitivity, was lost following injection of mepivacaine or bupivacaine. Pulvinar cell loss alone, induced by kainic acid injection, had no effect on relative motion sensitivity in the colliculus. The corticotectal tract lesions, but not the anesthetic injections, also had minor effects on flash-evoked responses and spontaneous discharge rates; these effects may reflect a retrograde response of some tectopulvinar cells to injury of their axons by the corticotectal tract lesions. In the colliculus opposite the corticotectal tract lesion, relative motion sensitivity was similar to that in normal animals. However, responses in the presence of a moving background were enhanced, suggesting that removal of cortical input to one colliculus may disinhibit the contralateral colliculus, a phenomenon reminiscent of the Sprague effect in the cat. We conclude that while cortical input to the colliculus may contribute little to the classic receptive field properties of superficial-layer cells, it clearly does contribute to relative motion sensitivity. PMID- 1493864 TI - Local norepinephrine depletion and learning-related neuronal activity in cingulate cortex and anterior thalamus of rabbits. AB - Multi-unit neuronal activity was recorded in posterior cingulate cortex (area 29) and the anterior ventral (AV) thalamic nucleus during discriminative instrumental avoidance learning wherein a response (stepping in an activity wheel) to a 0.5-s tone (CS+) prevented a foot-shock 5 s after CS+ onset. Presentations of a different tone (CS-) on 50% of the conditioning trials in an irregular sequence with the CS+ did not predict shock and thus required no response. Two groups of rabbits received intracranial micro-injections of 6-hydroxydopamine (6-OHDA) to locally deplete the NE in area 29 or the AV nucleus. Vehicle was injected in the non-depleted area in each group and a third group received vehicle injections in both areas. Dopamine neurons in subjects that received 6-OHDA were protected by pre-treatment with GBR-12909. Neuronal data were collected during two pre training sessions in response to the tones only and when the tones and shock were presented unpaired. Thalamically depleted rabbits made more, and cortically depleted rabbits made fewer, avoidance responses than controls during the early stages of behavioral acquisition, and cortically depleted rabbits made fewer responses than controls and thalamically depleted rabbits during extinction testing administered after the completion of acquisition. One effect of NE depletion on neuronal activity was entirely local: elimination of neuronal sensitization effects (enhanced discharges elicited by tones during the unpaired tone-shock pre-training treatment relative to pre-training with tones only). Other neuronal effects of NE depletion were system-wide, i.e., they occurred whether the depletion was cortical or thalamic.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1493865 TI - Responses of cat ventroposterolateral thalamic neurons to vibrotactile stimulation of forelimb footpads. AB - Responses of neurons in the ventroposterolateral nucleus of the thalamus to vibration applied to the forelimb footpads were analyzed in anesthetized cats in order to describe the signalling properties of thalamic neurons that received input from the different classes of tactile afferents innervating the glabrous skin of the distal forelimb. Seventy-six thalamic neurons, the majority of which (60 of 76) were positively identified as thalamocortical projection neurons, were classified into two broad groups according to their responses to 1-s step indentations of the skin. A minority (24%) comprised neurons that had slowly adapting (SA) responses, whereas the remainder (76%), the dynamically sensitive neurons, had transient responses to the onset and offset phase of the step and were further classified according to their sensitivity to cutaneous vibrotactile stimuli into those activated by low-frequency vibration (rapidly adapting, RA, neurons) and those activated by high frequencies (Pacinian afferent, PC, neurons). Thalamic RA neurons displayed phaselocked responses to vibration at frequencies up to approximately 100 Hz, while PC neurons displayed phaselocked responses to vibration up to 400-500 Hz. Thalamic SA neurons varied in their responses to vibrotactile stimuli; half were most sensitive to vibration frequencies of 50 Hz or less, while the others responded over a broader range of frequencies. Although three major classes of footpad-related thalamic neurons were identified, there was evidence of convergent input to a small proportion of them. The study demonstrates that thalamic neurons have the capacity for responding to cutaneous vibration with phaselocked, patterned impulse trains, which would enable them to encode information about vibrotactile frequencies up to approximately 300 Hz. PMID- 1493867 TI - Somatosensory evoked potential correlates of psychophysical magnitude estimations for air-puff stimulation of the foot in man. AB - Short air-puff stimuli were applied to the sole of the right foot to obtain both psychophysical and neurophysiological responses. The detection threshold (So) was first determined, and six levels of stimulus intensity above threshold were adopted for magnitude estimation. Somatosensory evoked potentials (SEPs) were also recorded over the foot projection area (2 cm posterior to Cz) for the six stimulus intensities. Six components (N40, P45, N55, P70, N80 and P90) were recorded within 100 ms following stimulation. A power function with an exponent of 0.94 provided an adequate description of the magnitude estimation values as a function of stimulus intensity, as was verified by the high correlation coefficient (r = 0.87; P < 0.001). Similarly, stimulus-amplitude functions of P45 N55, N55-P70 and P70-N80 SEP components were well represented by power functions with exponents of 0.62, 0.63 and 0.78, respectively. The SEP latencies as a function of stimulus intensity had negative power functions. The latency functions of the P45 and N55 components had the largest negative power exponents (-0.17 and -0.15) and showed the highest negative correlations (r = -0.70 and 0.71, respectively) with the stimulus intensity. These results suggest that both the amplitude and the latency information encoded in the SEPs may contribute to the magnitude estimation of the stimulus. PMID- 1493866 TI - Projections from fetal neocortical transplants placed in the frontal neocortex of newborn rats. A Phaseolus vulgaris-leucoagglutinin tracing study. AB - Fetal rat neocortex grafted into lesion cavities made in the newborn rat neocortex can exchange multiple axonal connections with the host brain. Most previous studies demonstrating efferent transplant-to-host brain connections have used fluorescent retrograde tracers injected into the host brain (Castro et al. 1985, 1987; Floeter and Jones 1984; O'Leary and Stanfield 1989). Other studies have used anterograde axonal tracing with either tritium-labelled amino acids impregnating the transplant and its efferents (Floeter and Jones 1985) or horseradish peroxidase injected into the transplants (Chang et al. 1984, 1986). In the present study we used the anterograde axonal tracer Phaseolus vulgaris leucoagglutinin (PHA-L) to examine in detail the course and termination of the efferent neocortical graft fibers. Twenty-six newborn rats had the right frontal cortex forepaw area removed by vacuum aspiration, while anesthetized by hypothermia. A piece of fetal frontal cortex 14-16 embryonic days old (E14-16) was immediately thereafter placed in the lesion, and the recipient rats allowed to survive for 5-7 months. At this time the rats were reoperated under sodium pentobarbital (Nembutal) anesthesia and the transplants iontophoretically injected with PHA-L. Two weeks later the animals were again anesthetized, perfused, and processed for PHA-L immunocytochemistry and routine histology. Analysis of acetylcholinesterase- (AChE) and Nissl-stained sections showed graft survival in 19 of the 26 animals used in this study. When these 19 brains were processed for PHA-L immunocytochemistry, 5 of them were found with certainty to have the PHA-L injection confined to the transplant. Based on these cases PHA-L reactive fibers arising from labelled transplant neurons were traced into the ipsilateral host neocortex adjacent to the transplant and found to project through the subcortical white matter to the ipsilateral parietal neocortical area 1, and claustrum. Callosal fibers were traced to the contralateral frontal neocortical forelimb and parietal areas. Transplant fibers were also observed to descend through the caudate putamen in the dispersed fiber bundles of the internal capsule to distribute as terminal branches and varicose fibers within the mesencephalic periaqueductal gray, red nucleus, deep mesencephalic nucleus, and intermediate gray of the superior colliculus, as well as in the pontine gray. Similar fibers and terminations were present in the caudate putamen, the reticular, ventrobasal, centrolateral, posterior, and parafascicular thalamic nuclei.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1493868 TI - Three-dimensional drawings in isometric conditions: planar segmentation of force trajectory. AB - Normal human subjects grasped an isometric handle with an unrestrained, pronated hand. They were asked to exert forces continuously to draw lemniscates (figure eights) in specified or self-chosen planes and in the presence or absence of a three-dimensional visual feedback cursor and a visual template. In every condition, the mean plane orientation in the force space differed appreciably between the two loops of the figure, as described previously by Soechting and Terzuolo (1987a) for free drawing arm movements. These findings suggest that the planar segmentation of the motor trajectory is not a consequence of joint motion but arises from central constraints related to the production of motor trajectory in space. PMID- 1493869 TI - Category-related components in visual evoked potentials: photographs of faces, persons, flowers and tools as stimuli. AB - One hundred and sixty black-and-white photographs of faces, persons, tools and flowers constituted the four stimulus categories in the first experimental paradigm. In the second paradigm, 160 black-and-white photographs of persons in a neutral (side view), fighting, greeting and "depressed" postures were used. The same nine female and nine male students volunteered as subjects in both paradigms. EEG responses were recorded through the electrodes F3, F4, Cz, Oz, T5 and T6 and referenced to "linked" mastoid electrodes. Individually averaged EPs and grand averages of the EPs for all 18 subjects were computed as well as bipolar responses for selected pairs of electrodes. Category-related components in the evoked potentials (EPs) were found mainly in the recordings through the midline and the frontal electrodes. These category-specific differences were more prominent, however, in the bipolar recordings between these electrodes and the respective ipsilateral electrodes (T5 or T6) than in the monopolar recordings. Monopolar and bipolar EPs could be divided into those evoked by person stimuli and by non-person stimuli. Category-related differences were demonstrated by computing EP-difference curves related to pairs of stimulus categories. In addition to the statistical analysis of peak amplitudes and peak latencies of the individual curves, a "running" Wilcoxon test was applied and cross-correlation functions between the EPs evoked by different stimulus categories were computed. The "face-related" components of the EPs described in earlier studies could be confirmed. They were prominent in the waves peaking between 130 and 150 ms and between 200 and 230 ms and were stronger when faces rather than full-figure "neutral persons" were used as stimuli. No significant hemispheric differences could be found between any of the EPs. In the second paradigm, EEG responses evoked by person stimuli in a neutral, fighting, greeting or depressed posture exhibited only slight differences, if at all. The "person-responsive" components in the EPs evoked by the photographs of a neutral standing person (side view) were smaller between 120 and 200 ms than in the other three categories in which "expressive" persons were the stimuli. PMID- 1493870 TI - Identification and characterization of a Giardia lamblia group-specific gene. AB - Giardia lamblia consist of heterogeneous isolates that can be divided into at least three groups. Differential screening of a cDNA library with isolate specific antisera identified a gene which is expressed and found only in Group 3 isolates. This gene, GLORF-C4, is 597 bp in length and predicts a deduced protein of 198 amino acids that is characterized by a polyserine motif. Giardia can also be grouped by their ability to express certain variant-specific surface proteins (VSPs), expression of which is restricted among groups. In Southern blots, probes specific to two VSPs were used to characterize isolates. Failure to detect VSP genes correlated with inability to express the same VSP. Analysis of isolates with these new probes complements and confirms the groupings previously suggested using other criteria. These genetic differences should allow differentiation of isolates and permit the application of basic epidemiological techniques to determine the manner of spread and the presence of animal reservoirs. PMID- 1493871 TI - Experimental Plasmodium falciparum cerebral malaria in the squirrel monkey Saimiri sciureus. AB - Infection of the squirrel monkey, Saimiri sciureus, with several strains of Plasmodium falciparum leads in a proportion of animals to neurological symptoms with a fatal outcome. This first simian model for human cerebral malaria was studied with three strains of parasites, the uncloned Palo Alto(FUP-1) strain, the Palo AltoPLF3 clone MHB11, and the recently monkey-adapted P. falciparum strain IPC/RAY. Cerebral malaria could develop during primo infection of monkeys, whether the animals had been splenectomized or not. It did not occur in all animals and the appearance of neurological symptoms could not be predicted, as it was not related to the degree of parasitemia or duration of parasite infections. PMID- 1493872 TI - Plasmodium falciparum: chymotryptic-like proteolysis associated with a 101-kDa acidic-basic repeat antigen. AB - Malaria proteinases appear to function in the release of merozoites from infected erythrocytes and the invasion of merozoites into erythrocytes. Chymostatin, an inhibitor of chymotrypsin-like proteinases, inhibits malaria invasion and also inhibits apparent autoproteolysis of a 101-kDa acidic-basic repeat antigen (p101 ABRA) that is found in the vacuolar space surrounding merozoites in Plasmodium falciparum-infected erythrocytes. After purification by a monoclonal antibody (MAb 3D5), p101-ABRA degrades into smaller fragments in the absence of chymostatin. In this study fluorogenic proteinase substrates of the type peptidyl 7-amino-4-trifluoromethyl coumarin with phenylalanine or tyrosine linked to AFC were used to characterize chymotryptic-like activity associated with p101-ABRA. When p101-ABRA from the cell extract of P. falciparum-schizont-infected erythrocytes was affinity purified on MAb 3D5 beads, chymotryptic-like activity bound to the beads. Seventy-four percent to 96% of the activity detected using MeOSuc-KLF-AFC, Suc-LLVY-AFC, or SY-AFC at a pH optimum of 7.0 was removed from the extract and 6 to 33% was detected on the washed beads. Attempts to recover active enzyme eluted from the beads were not successful. Enzymes cleaving two other substrates (MeOSuc-AAPM-AFC and F-AFC) did not significantly bind to mAB 3D5 beads. Chymotryptic-like activity was also associated with p101-ABRA in fractions from sequential DEAE-Sephacel chromatography, Sephacryl S-200 chromatography, and nondenaturing polyacrylamide gel electrophoresis. PMID- 1493873 TI - The identification of a variant form of cystathionine beta-synthase in nematodes. AB - Characterization of the physical and catalytic properties of the enzyme responsible for nematode "activated L-serine sulfhydrase" activity (L-cysteine + R-SH-->cysteine thioether + H2S) has led to its identification as a novel, variant form (allelozyme) of cystathionine beta-synthase that is distinct from a mammalian-type synthase also present in nematodes. Additional work has demonstrated the ability of live Panagrellus redivivus to produce H2[35S] from exogenous L-[35S]cysteine and 2-mercaptoethanol, thus providing preliminary evidence for the in vivo operation of the activated L-serine sulfhydrase reaction in nematodes. PMID- 1493874 TI - Schistosoma mansoni: hycanthone/oxamniquine resistance is controlled by a single autosomal recessive gene. AB - Individual schistosomes of an hycanthone/oxamniquine-sensitive strain were crossed with individual schistosomes of the opposite sex and belonging either to the same sensitive population or to a different strain which exhibited high resistance to the two drugs. Schistosome crosses were performed by transfer of single worm pairs into the mesenteric veins of mice and the drug sensitivity/resistance of individual progeny worms was assessed using an in vitro test. Drug resistance behaved as an autosomal recessive trait, as shown by the results of the F1 and F2 generation and of the backcrosses. Drug-resistant worms appeared to be slightly less viable than their sensitive counterpart at all stages of the life cycle. The results are relevant for an interpretation of drug resistance and drug mechanisms and the approach used in this study may be applicable to different genetic markers in schistosomes. PMID- 1493875 TI - Leishmania tropica infection in hamsters and a review of the animal pathogenicity of this species. AB - Four strains of Leishmania tropica s. st. from Afghanistan were found to be constantly infective to the golden hamster (Mesocricetus auratus), whether inoculated as culture promastigotes from early passages or as amastigotes from the cutaneous lesions. In total, 66 amastigote passages were carried out over 6 passage generations. The footpad lesions were chronic and nonulcerative infiltrates; their evolution is described up to 15 months. No self-healing was observed. Balb/c mice and gerbils were not susceptible. Earlier studies on L. tropica s. st. in laboratory animals, principally by Soviet and French workers, are critically reviewed. This new experimental model of chronic cutaneous leishmaniasis is of special interest for studies on the immunology and chemotherapy of the disease. Some advantages over the commonly used L. major model are discussed. PMID- 1493876 TI - Leishmania major and Leishmania donovani: effect of LPG-containing and LPG deficient strains on monocyte chemotaxis and chemiluminescence. AB - Lipophosphoglycan (LPG) is a major glycolipid present on the membrane of Leishmania promastigotes and amastigotes. We have previously shown that preincubation of peripheral blood monocytes with purified LPG inhibits IL-1 production, chemotactic locomotion, and luminol-dependent chemiluminescence (LDCL). In the present study we tested the effect of LPG present on live parasites on monocyte activity. For this purpose, we used two mutant strains deficient in LPG and two LPG-containing strains. One pair was Leishmania major and the other Leishmania donovani. Monocytes in suspension were infected with the different parasite strains and tested for chemotactic locomotion and LDCL at different times between 1 and 72 hr after infection. In parallel, the percentage of infected monocytes was measured in stained cytospin preparations. The results obtained showed that at 1 hr of incubation only the LPG-containing strains inhibited chemotaxis, while the mutant strains showed a normal response. From 4 hr of incubation onwards, the mutant strains also inhibited monocyte chemotactic locomotion. LDCL was only slightly inhibited by the LPG-containing strains after 1 hr, because of a high level of spontaneous stimulation, probably due to phagocytosis. At 24 and 72 hr all strains inhibited LDCL. These results suggest that LPG is responsible for early inhibition of macrophage activity, but that other factors are responsible for inhibition at later stages of in vitro infection. The model described here might represent a useful tool to further analyze the mechanisms involved in immune evasion of Leishmania parasites. PMID- 1493877 TI - Plasmodium vinckei petteri: identification of the stages sensitive to arteether. AB - Antimalarial activity of arteether, a derivative of artemisinin (qinghaosu) against blood-induced infections of the highly synchronous Plasmodium vinckei petteri rodent species of malaria was evaluated in Swiss mice. A single subcurative dose of arteether of 2.2 mg/kg body weight was injected subcutaneously to mice, either during the prepatent period or during the patent infection, when different stages of the parasitic cycle were present in the blood. It was shown that rings and young trophozoites were the most susceptible stages to arteether. The drug had no effect on merozoites and little effect on mid-term trophozoites which is the stage most sensitive to chloroquine. The alcoholic solution (10% alcohol in sterile water) had an immediate effect while the oily solution (miglyol 840) was active between 3 and 21 hr after injection. PMID- 1493878 TI - Onchocerca volvulus: frequency of codon usage. PMID- 1493879 TI - Survey of sulphites determined in a variety of foods by the optimized Monier Williams method. AB - A survey of sulphite levels in a variety of foods including dried fruit, dried mashed potatoes, shrimp, canned mushrooms and fruit juices has been conducted. The levels found ranged from 0 ppm in orange juice to 3722 ppm as sulphur dioxide in dried fruit. The foods were analysed by the optimized Monier-Williams procedure. PMID- 1493880 TI - Potential weekly intake of artificial food colours by 3-14-year-old children in Brazil. AB - The Potential Weekly Intake (PWI) of artificial food colours by 3-14-year-old children living in the District of Barao Geraldo, Campinas, Sao Paulo, Brazil, was estimated on the basis of average consumption data of artificially coloured food and analytically determined colour concentration in foodstuffs ingested. Coloured food consumption data were obtained through dietary recall interviews and collection of the packages and/or labels of the coloured foods consumed during a two-week period. Colours found in the individual types of foods detected through the consumption survey were identified and determined by methods that included wool dyeing and polyamide column extractions, ascending paper chromatography and spectrophotometry. The results showed that all artificial colours used in the composition of 83 commercial food products, including jellies, juices, soft drinks, syrups and 57 different candies, were permitted for use in food in Brazil the year the survey was conducted (1986), in amounts below those prescribed by law. Statistical analysis performed to compare the PWI for different population groups demonstrated that young male children, especially from lower social classes, were most exposed to artificial colours. Comparison of the estimated potential intakes with the toxicologically Acceptable Daily Intake (ADI) showed that consumption of Amaranth, Sunset Yellow, Indigotine and Tartrazine by all children in the study represented approximately 24%, 3%, 0.05% and 0.4%, of the actual ADI values, respectively. PMID- 1493881 TI - Migration of polyisobutylene from polyethylene/polyisobutylene films into foods during domestic and microwave oven use. AB - Migration of polyisobutylene from polyethylene/polyisobutylene film into foods has been studied in domestic applications such as wrapping of foods and reheating in a microwave oven. The results of these migration studies were obtained by direct measurement using newly developed analytical methods utilizing nuclear magnetic resonance (NMR) and infra-red (IR) spectroscopy as well as predictively from assessment of loss of polyisobutylene from the film. Total levels of polyisobutylene migration into cheese were found to be 8-10 mg/kg, into cake 1-5 mg/kg, and into sandwiches ranged from < 1 to 4 mg/kg. Reheating foods covered with film in the microwave oven, gave migration levels ranging from < 0.01 mg/kg for contact with steam only, up to 0.5 mg/kg for severe splashing of food onto the film and 4 mg/kg for reheated pizza. Migration of polyisobutylene was shown to be skewed towards the low molecular weight fraction of the additive. In typical films, the molecular weight range of polyisobutylene was shown to be 300 6000 daltons (95% limits) centred on 1300 daltons, whereas the additive that had migrated into cheese was found to range from 130-2200 daltons, centred on 520 daltons. PMID- 1493882 TI - Isolation and determination of zearalenone in rice cultures using liquid chromatography with diode array detection. AB - A rapid method is described for the isolation and determination of zearalenone (ZEN) produced by Fusarium spp., in moist rice culture. Following a simple solvent extraction using acetonitrile:water, the crude extract was defatted with hexane and diluted with methanol. The extract solution containing ZEN was evaporated to dryness, the residue dissolved in acetonitrile and diluted with water. The solution was analysed by liquid chromatography using a UV-diode array detector. The UV spectra and chromatographic data generated from the standard ZEN was stored in a computer and used to identify the toxin in a crude mixture. The purity of the separated peak and the amount of toxin in the crude mixture was determined. The present technique is fast and allows the acquisition of UV spectral information and chromatographic data of ZEN in a single chromatographic operation. Recovery of zearalenone added to the rice was 76-94%. PMID- 1493883 TI - Factors affecting the results of T-2 mycotoxin ELISA assay. AB - Certain substances in the sample may increase or decrease the reaction between the enzyme and substrate in ELISA assays. During a survey of T-2 trichothecene in food and animal feed 75% of milled grain samples gave a higher O.D. value in competitive T-2 toxin ELISA than the negative control. In samples spiked with small quantities (10 micrograms/kg) of T-2 toxin this type of reaction resulted in underestimates of toxin content. However, the effect was weak and, owing to the high sensitivity of the assay, it did not result in false negative reactions. The low efficiency of the carrier solvent and natural peroxidases in food and feed were considered to be the cause of the inaccurate reactions. A few fermented and processed foodstuffs and feed gave positive results in the T-2 toxin ELISA assay, but verification of the results by gas chromatography (GC) showed that the reactions were false. Certain substances in the samples destroyed or decreased the enzyme activity. False positive reactions can be distinguished from correct ones by retesting the extracts in different dilutions. PMID- 1493884 TI - The cyanobacterium Oscillatoria erythraea--a potential source of toxin in the ciguatera food-chain. AB - A compound lethal to mice (i.p.) was extracted from samples of Oscillatoria erythraea, four species of mollusc and one species of molluscivorous teleost collected from the south-east coast of Queensland, Australia, during and shortly after O. erythraea blooms. The compound was chemically indistinguishable from ciguatoxin (CTX) on the basis of solvent extraction and partitioning and silicic acid chromatography. Residues derived from toxic samples elicited signs of intoxication, death and histopathological changes in mice, consistent with extracts of ciguatoxic material. Stick enzyme immunoassay tests and thin layer chromatography assessment of extracts indicated the presence of ciguatoxin-like polycyclic ether(s). O. erythraea is implicated as a potential elaborator of a CTX-like compound in the tropical marine biota. PMID- 1493885 TI - Lead intoxication in cattle: a case report. AB - During the autumn of 1989 a feed contamination induced a widespread lead intoxication of cattle in the northern provinces of The Netherlands (Groningen and Friesland). Over 300 farms were involved, affecting about 15,500 animals (mostly dairy cattle). For a period of one to four weeks these animals took up a thousand kg of lead. This resulted in lead levels in milk, livers, and kidneys above the regulatory safety limits. Due to the chelating therapy, which was rapidly applied by the local veterinarians, only about 30 animals died of an acute lead intoxication. A joint action of the governmental and private authorities prevented exposure of consumers to lead-contaminated animal products. Based on observations, measurements and literature data, predictions were made of the lead levels to be expected in animal products and the time needed for depletion of these levels. The appropriate animals were ear-tagged to ensure their identification, and the decline in time of the lead levels in milk and offals was conscientiously monitored. In the second week of 1990 the lead concentrations were decreased to levels well below the regulatory limits, and hence the tags were removed. The present paper reports our observations and conclusions, especially regarding treatment, predictions and outcome of this incident. PMID- 1493887 TI - [Fulminant hepatitis caused by wild germander]. PMID- 1493886 TI - Changes in cassava toxicity during processing into gari and ijapu--two fermented food products. AB - Grated cassava to which tap water was added at levels of 25%, 50% and 75% (v/w) was held at 30 degrees C, 40 degrees C or 50 degrees C and examined over a 6 h period for cyanide content, pH and titratable acidity (TTA). During the come-up time, i.e. the time between addition of water and attainment of desired holding temperature (between 14 and 47 min), reductions in bound cyanide of ca 54-85% occurred, depending on the level of added water and holding temperature. The corresponding losses for the control samples, to which no water was added, were ca 25-33%. The biggest reduction in the bound cyanide of > 99% (from 89.0 to 0.6 ppm) occurred in grated cassava with 75% added water held at 50 degrees C. There was little or no change in pH during the period of study. The reduction of processing time for certain cassava products based on separation into detoxication and flavour development/fermentation stages is discussed. PMID- 1493888 TI - [Liver abscess caused by Streptococcus milleri]. PMID- 1493889 TI - [Duodenal hematoma secondary to a hemostatic injection of adrenaline for hemorrhagic duodenal ulcer]. PMID- 1493890 TI - [Gastrin and colorectal cancer: cause or consequence?]. PMID- 1493891 TI - [Efficacy of paromomycin sulfate (Humagel) in an AIDS infected patient with intestinal cryptosporidiosis]. PMID- 1493892 TI - [Ischemic colitis after cocaine abuse]. PMID- 1493893 TI - [Acute hemorrhagic colitis after ingestion of amoxicillin]. PMID- 1493895 TI - [Hepatotoxicity: also, phytotherapy]. PMID- 1493894 TI - [Short and long-term effects of clonidine on sympathetic activity, hemodynamics and renal metabolism of water and sodium in patients with liver cirrhosis]. PMID- 1493896 TI - [Hepatitis observed during a treatment with a drug or tea containing Wild Germander. Evaluation of 26 cases reported to the Regional Centers of Pharmacovigilance]. AB - Twenty-six patients developed acute hepatitis after taking Germander, an herbal medicine used to facilitate weight loss. Hepatitis occurred within 9 weeks of treatment and was characterized by jaundice and a high level of aminotransferases. Recovery was obtained between 1.5 and 6 months after withdrawal. In 12 cases, readministration was followed by prompt recurrence of hepatitis. The causal relationship is probable but the mechanism remains unclear: there was no relationship with the daily intake and the duration of treatment; there are no toxicological data on Germander compounds; contamination by an unidentified product is possible but has not been demonstrated. It should be emphasized that readministration of Germander produced recurrence of the hepatitis whenever it was performed. As a result, the French Ministry of Health recently decided to prohibit national-wide all Germander containing medicinal products. PMID- 1493897 TI - [Hepatitis B virus vaccine. Evaluation and perspectives]. PMID- 1493898 TI - [Ultrasound endoscopy and digestive cancers]. PMID- 1493899 TI - [Barrett's esophagus, gastroesophageal acid reflux and duodenogastric reflux during the digestive and postprandial period]. AB - Pathologic gastroesophageal acid reflux appears to be involved in the pathogenicity of Barrett's esophagus. The possible pathogenic role of duodenogastric reflux, however, has been suggested by several studies. The aim of this prospective study was to assess the prevalence of acid or duodenogastric reflux in patients with Barrett's esophagus. Nine patients with histologically proven Barrett's esophagus (mean length: 7.7cm; range: 2-13 cm) were studied by esophageal manometry and 24 hour pHmetry. Duodenogastric reflux was measured in the interdigestive period by aspiration and during the postprandial period using an isotopic method. The results of these different investigations were compared with healthy volunteers (n = 20 to 27). Three patients had complicated Barrett's esophagus (Barrett's ulcer: n = 2, high-grade dysplasia: n = 1). The results of the different investigations showed that a) all patients had abnormal acid exposure and an esophageal motor dysfunction (decrease in lower esophageal sphincter pressure, amplitude and duration of contractions and increase in percentage of peristaltic dysfunction); b) none of the patients had any pathologic duodenogastric reflux neither in the interdigestive nor in the postprandial period. These results a) confirm the high prevalence of acid reflux in patients with Barrett's esophagus, b) show that bile or pancreatic secretions are not involved in the pathogenicity of Barrett's esophagus. PMID- 1493900 TI - [Medical behaviors and cancer of the exocrine pancreas]. AB - A French national enquiry examined 4,530 cases of cancer of the exocrine pancreas treated from 1982 to 1989. Ultrasonography was performed in 98% of cases. Other radiological or biological investigations varied from one department to another (P < 0.001). Of 769 patients seen in Gastroenterology departments, 47% (range: 0 to 72%) were operated on. Of 3,761 patients undergoing operation, surgical techniques differed significantly from one department to another (P < 0.001). Resections were performed in 21% (range: 2 to 45%) of cases. Causes of unresectability, choice of biliary bypass, indications for gastrojejunostomy, and use of splanchnicectomy varied from one surgical department to another (P < 0.01). Wide variance in therapeutic policies may be explained by differences in local indications or surgical expertise, giving support to the need for a consensus conference to discern the indications of the available therapeutic alternatives for cancer of the exocrine pancreas. PMID- 1493901 TI - [Changes in gastrointestinal mucins caused by attapulgite. Experimental study in rats]. AB - A histochemical study was carried out to evaluate the changes occurring in mucins secreted by the rat stomach and intestine following a 7 day-treatment with a cytoprotective clay: attapulgite. Staining of gastrointestinal sections was performed with periodic acid-Schiff reagent, alcian blue pH 2.5 and pH 1.0, and with lectin conjugated with horseradish peroxidase for detecting complex carbohydrates. When compared with controls, attapulgite induced an increase in carboxylic mucin content in the cells of the crypts associated with a decrease in sulphated mucins and in binding with soy bean agglutinin in surface epithelial cells in the fundic zone. In the antrum, staining with wheat germ agglutinin was decreased in the crypt cells while Ulex europaeus agglutinin affinity was increased in the glandular cells. The duodenum was characterized by increased binding with Ulex europaeus agglutinin in Brunner's glands. These results show that the polysaccharidic components of the gastrointestinal glycoproteins are modified by attapulgite, and this mechanism may be involved in its cytoprotective effects. PMID- 1493902 TI - [Transanorectal ultrasonography in the evaluation of extension and the monitoring of epidermoid cancers of the anus treated by radiation or chemotherapy]. AB - Twenty-five consecutive patients (5 men and 20 women) with squamous cell anal carcinoma were evaluated by transanorectal ultrasonography (TRUS). The patients were treated with radiotherapy alone (6 cases) or combined concomitant radiotherapy and chemotherapy (19 cases). The ultrasound findings were compared with clinical stage as assessed by digital examination and with pelvic computed tomography. Four tumors in clinical stage T2 showed evidence of external sphincter involvement at ultrasound (UT3) and one tumor in clinical stage T1 showed an invasion of the internal sphincter at ultrasound examination. Low echogenic, rounded structures, interpreted as enlarged lymph nodes, were identified in 8 cases at ultrasound but were not seen with computed tomography. Ultrasonograms were also obtained one month after the achieved end of radiation. Correct staging was by TRUS and CT in 92% and 72% of cases respectively. When combining clinical stage with TRUS, all tumors classified as T1-T2, UT1, UT2 had a complete response to radiotherapy with or without concomitant chemotherapy. TRUS could be a useful adjunct to digital palpation in initial staging and in follow-up after medical treatment of anal canal carcinoma. PMID- 1493903 TI - Isolation of a new restriction enzyme, ApaCI, an isoschizomer of BamHI produced by Acetobacter pasteurianus. AB - A new Type II restriction endonuclease ApaCI purified from Acetobacter pasteurianus is an isoschizomer of BamHI that cleaves at the nucleotide sequence 5'-G/GATCC-3' of double-stranded DNA. The single restriction activity present in this strain permits rapidly purified 30,000 units of cleavage activity from 10 g of freshly harvested cells. The resulting ApaCI preparation is free of contaminant nuclease activities that might interfere with in vitro manipulation of DNA. PMID- 1493904 TI - Permeability factor, cytotoxicity and serotyping of Pseudomonas aeruginosa strains. AB - We analyzed in detail the permeability and cytotoxic activity as well as the serotypes of 127 Pseudomonas aeruginosa strains. Sixty-seven strains were isolated from immunocompromised patients (51 from patients with tumors and 16 from patients after transplantation) and 60 strains were isolated from patient's ears. Culture filtrates of strains isolated from patients after transplantation were responsible for the highest part of permeability reactions corresponding to an intermediate toxin production (68.8%) (categories 2 and 3) and culture filtrates of strains isolated from patients with tumors caused the highest percentage of permeability reactions corresponding to a strong toxin production. Culture filtrates of strains isolated from ears of patients were responsible for the highest percentage of negative permeability reactions (15%). With positive permeability reaction size (categories 2-6) increased also the percentage of cytotoxicity as well as the intensity of morphological changes on Vero cells after 1 and 2 d. We did not observe any relationship between a particular permeability reaction category and the most frequent serotypes (O4, O6) or nontypable strains of the tested groups. PMID- 1493905 TI - The effect of an antigenic stimulation on proliferative response in athymic mice. AB - The proliferation activity of the main cellular categories of bone marrow after infusion of 3H-thymidine was studied in nu/nu and +/+ 1-month- and 3-month-old BALB/c mice in comparison with lymphoid cells in the spleen and mesenteric lymph nodes. The stem cell defect in nu/nu mouse bone marrow is compensated by an increased proliferation in myeloid series and in agranulocytes. The increase of proliferation activity among lymphoid cells in peripheral lymphoid organs was observed only in the 3-month-old mice with a delay in the nudes. PMID- 1493906 TI - Pesticidal activity of virginiamycins S1 and M1. AB - Virginiamycins S1 and M1, two major components of the antibacterial antibiotic complex produced by Streptomyces virginiae and used as an animal growth promoter in animal husbandry, exhibited a selective insecticidal activity against Leptinotarsa decemlineata comparable with the effect of the organophosphorus pesticide Metathion. An acaricidal effect of the two compounds on eggs of Tetranychus urticae was also observed. PMID- 1493907 TI - Age-related distribution of cells in cell cycle phases in dependence on specific rate of growth in chemostat cultures of Candida utilis. AB - Individual cells in chemostat cultures of Candida utilis (D = 0.05, 0.1, 0.2, 0.25, 0.3 and 35/h) were analyzed according to the number of bud scars and according to their position in the cell cycle. The distribution in the cell cycle phases depends both on the genealogical age and the specific rate of growth. PMID- 1493908 TI - Role of blast cell immunophenotyping for the diagnosis and prognosis of acute myeloid leukemia. AB - Bone marrow blast cell antigen expression from 86 patients with de novo acute myeloid leukemias (AML) was studied and correlated with FAB classification and clinical outcome. Among a panel of 14 monoclonal antibodies routinely used for the diagnosis of acute leukemias we studied the expression of six antibodies (CD13, CD15, VIM2, CD33, CD14, CD34) of the granulomonocytic lineage and found that some of them were useful for diagnosis and/or prognosis. For FAB subclassification of AML, the CD13 or VIM2 antigen expression was of no benefit. Monocytic leukemias (M4 + M5PD + M5WD) more frequently expressed CD34 antigen (28/31) than granulocytic (M1 + M2 + M3) subtypes (33/53) (P < 0.01). Finally, the most striking differences were found with CD14 antigen expression: CD14 antigen was more frequently expressed in M4 + M5 leukemias (21/31) than in M1 + M2 + M3 subtypes (12/33) (P < 0.01). The mean percentage of CD14 positive blast cells was accordingly higher in monocytic leukemias than in granulocytic leukemias and the difference was highly significant (P < 0.0001). The CD15 antigen was more frequently expressed in differentiated leukemias (M2 + M3 + M4 + M5WD) (35/44) than in poorly differentiated forms (M1 + M5PD) (17/37) (P < 0.001). The statistical difference was higher when the mean percentage of CD15 positive blast cells were compared (P < 0.0003). Moreover these latter percentages were different in M1 and M2 subtypes (P < 0.003). The blast cell expression of CD13, CD14, CD15 or CD33 was not predictive of the length of CR or survival. Moreover, our results support previously published findings suggesting a longer overall survival duration for patients whose leukemic cells do not express the CD34 antigen (P < 0.01). We also confirm that patients with the more differentiated subtypes of AML (CD13-, CD34+) tend to survive longer than patients with the less differentiated subtypes of AML (CD13-, CD34+) (P < 0.001). PMID- 1493909 TI - The management of acute myelogenous leukemia in the elderly: ten-year experience in 118 patients. AB - This retrospective study was undertaken to analyse the survival pattern of 118 consecutive, unselected patients with acute myelogenous leukemia (AML) aged between 60 and 82 years observed at a single centre over a 10-year period (1981 1991). Thirty-two per cent of cases had an antecedent hematological disorder (AHD), and 7 per cent had a secondary AML. Forty patients (39 per cent) were managed with palliative intent with short courses with oral hydroxyurea +/- 6 thioguanine. In contrast to 78 patients (61 per cent) selected for remission induction treatment, these were significantly older (P < 0.0001), had a greater incidence of AHD (P < 0.039) and of hypoplastic AML (P < 0.017), and an inferior amount of blast cells in the bone marrow (P < 0.003). Patients undergoing remission-induction chemotherapy were managed with DAT-like chemotherapy, high dose cytosine arabinoside (HD-ara-C), and mitoxantrone-based regimens. The complete response (CR) rate was 29 per cent. Response was higher with the two most intensive HD-araC and mitoxantrone-etoposide-araC programmes (P < 0.026), and correlated favourably with no AHD (P < 0.04) and lower blast cell count in the peripheral blood (P < 0.02). Overall survival of responders was longer than in palliation and nonresponder groups (P < 0.025 and P < 0.001, respectively). In the active treatment group, survival correlated with performance status (P < 0.005) and blast cell count (P < 0.05). Infection was the main cause of morbidity during active treatment, accounting for most induction failures (60 per cent), followed by haemorrhage (12 per cent) and resistant disease (12 per cent). These results from an unselected series represent an improvement over those obtained by us in previous years (1971-1980), and show that intensive treatment programmes are applicable to the elderly with AML and that prolonged disease-free survival is possible for some. Improving further CR rate and duration will depend equally on the optimization of supportive care measures and the introduction of more effective therapeutic modalities. PMID- 1493910 TI - Large cell lymphoma with initial presentation in the bone marrow. AB - This report describes 14 cases of large cell lymphoma with initial presentation as marrow involvement in the absence of peripheral lymphadenopathy. The disease affected mainly the middle-aged and elderly, with male predominance. Most patients presented with swinging fever and peripheral blood cytopenia. Reactive hemophagocytic syndrome was a common finding, causing significant morbidity and mortality. Peripheral lymphadenopathy was absent (by case selection), but involvement of the liver, spleen and paraaortic lymph nodes could be demonstrated in some cases. However, in some patients, the involvement was apparently restricted to the bone marrow. Involvement of the bone marrow was often subtle, and could be missed on causal examination. Immunohistochemical studies on eight cases showed that four exhibited a B-cell phenotype, three a T-cell phenotype and one a non-T non-B phenotype. The prognosis was poor, with survival being measured in days to weeks in most patients. PMID- 1493911 TI - A study of paternal age and sex ratio in sperm chromosome complements. AB - There is conflicting evidence as to whether the secondary sex ratio in humans decreases with paternal age. Such an age effect could be caused by an altered frequency in the production of X-chromosome and Y-chromosome-bearing sperm as a man ages. To study this possibility we analysed 9,225 sperm karyotypes from 143 men aged 21-55 years. Human pronuclear sperm chromosome complements were obtained after fusion with golden hamster oocytes. The percentage of X- and Y-chromosome complements was not significantly related to donor age. PMID- 1493912 TI - A haplotype-based 'haplotype relative risk' approach to detecting allelic associations. AB - A novel variation of the Haplotype Relative Risk (HRR) of Rubinstein et al. [Hum Immunol 1981;3:384] is proposed, in order to glean increased information about linkage disequilibrium or allelic associations by analyzing haplotype-based data rather than genotypic data. It is shown that statistical tests based on our design give much higher power than those based on the original HRR approach. Several additional nonparametric tests based on the same data are analyzed, and power is computed for each of them. Further, parametric likelihood methods are applied to testing linkage equilibrium, and estimating delta, the coefficient of linkage disequilibrium, from the same data. PMID- 1493913 TI - Genetic structures in the population of Veneto. AB - The genetic structures of the population residing in the provinces of Venice and Rovigo in the Veneto region at the north of the Po delta in Italy was studied in 1,210 individuals residing in 18 sampling areas, using the phenotype and gene frequencies of 7 red cell enzymes: acid phosphatase (ACP1), esterase D (ESD), glyoxalase I (GLOI), glutamic-pyruvic transaminase (GPT), 6-phosphogluconate dehydrogenase (6-PGD), phosphoglucomutase 1 (PGM1), and phosphoglycollate phosphatase (PGP). For the analysis of the distributions of phenotype and gene frequencies, standardized variance and kinship profiles were used. It was found that the genetic differentiation within each province is low, and that only two systems, GPT and PGP, are significantly different between the two provinces. The samples studied seem to belong to a mainly homogeneous population. PMID- 1493914 TI - Triple alpha-genes (alpha alpha alpha anti3.7) in a patient with sickle cell anaemia. AB - This paper reports the case of a 17-year-old male student from the Jaizan area in south-western Saudi Arabia who had sickle cell anaemia and possessed three alpha genes on one chromosome (alpha alpha alpha anti3.7) and two on the other. The clinical manifestations were severe, with frequent blood transfusion requirements and frequent episodes of painful crises, severe anaemia and tissue involvement. In comparison with age and sex-matched sickle cell anaemia patients with one alpha-gene deletion (-alpha/alpha alpha), or a normal alpha-gene arrangement (alpha alpha/alpha alpha), a more severe disease presentation was obvious in the propositus. It is suggested that with the surplus alpha-globin chains, more severe haematological and clinical abnormalities occur, these influence the phenotypic expression of sickle cell anaemia. However, more patients with this type of gene arrangement must be studied before a definite conclusion can be reached regarding the influence of excess alpha-globin chains on the presentation of sickle cell anaemia. PMID- 1493915 TI - Polymorphisms of alpha-1-acid (orosomucoid), alpha-2-HS-glycoproteins and alpha-1 B among the Parsis of India. AB - Genetic polymorphisms of plasma alpha 1-acid glycoprotein (oro-somucoid, ORM), alpha 2-HS-glycoprotein (A2HS) and alpha 1-B-glycoprotein (alpha 1B) were studied in a group of Parsis in Bombay, India. The frequencies of ORM1*1, ORM1*2 and ORM1*3 were found to be 0.636, 0.356 and 0.008, respectively. A2HS*1, A2HS*2 and A2HS*3 frequencies were 0.855, 0.135 and 0.010, while the frequencies of A1B*1 and A1B*2 were 0.881 and 0.119, respectively. The phenotype distribution at all three loci was at Hardy-Weinberg equilibrium. The ORM2 locus was monomorphic in the Parsis. PMID- 1493916 TI - Genetic polymorphisms of alpha-2-HS-glycoprotein, group-specific component and orosomucoid in the Han population, Chengdu, China. AB - The Han population in Chengdu, China, was investigated for genetic polymorphisms of alpha-2-HS-glycoprotein (A2HS), group-specific component (GC) and orosomucoid (ORM) using isoelectric focusing followed by immunofixation. The allele frequencies were: A2HS*1 = 0.6958,A2HS*2 = 0.3042, GC*1F = 0.4021, GC*1S = 0.3182, GC*2 = 0.2745, GC*1A = 0.0052, ORM1*F1 = 0.7028, ORM1*S = 0.2762, ORM1*F2 = 0.0210, ORM2*A = 0.9965, ORM2*Var = 0.0035. PMID- 1493917 TI - Alpha-1-antitrypsin (PI) subtypes in Russians and Poles. AB - alpha-1-antitrypsin (PI) subtypes were studied in Poles and Russians. The frequencies of the PI alleles were similar in the two populations, with the exception of the Z allele, whose frequency was significantly lower in Poles. The M3 allele frequency, which is highly heterogeneous in European populations, has medium frequencies in Poles and Russians. PMID- 1493918 TI - Polyclonal activation of B lymphocytes by lipopolysaccharide requires macrophage derived interleukin-1. AB - Lipopolysaccharide (LPS) is a potent murine polyclonal B-cell activator which induces cellular proliferation and IgM secretion. The precise role of activated macrophages in the induction of LPS-dependent, B-cell responses has been unclear. Although early reports concluded that the LPS effect occurs independently of other cell types, other studies have suggested that adherent macrophages exert either potentiating or inhibitory effects. In the present study, B-cell mitogenesis and IgM production were measured in primary spleen cell cultures after removing adherent cells by a variety of experimental procedures. B-cell activation by LPS was found to be strictly dependent on the presence of adherent macrophages. Antibody neutralization and cytokine reconstitution studies demonstrated that macrophage-derived interleukin- (IL-1) is a necessary co-factor for LPS-induced polyclonal activation. PMID- 1493919 TI - Comparative responses of human and rabbit interleukin-1 in vivo: effect of a recombinant interleukin-1 receptor antagonist. AB - The ability of recombinant human and rabbit interleukin-1 alpha (IL-1 alpha) in inducing inflammatory responses in rabbit skin were compared. Intradermal (i.d.) injections of recombinant human IL-1 alpha and recombinant rabbit IL-1 alpha induced intense accumulation of 111In-labelled neutrophils which was dependent on the dose of the cytokines administered. Both forms of IL-1 alpha induced very small levels of plasma protein leakage. Co-injection of the cytokines with the mRNA synthesis inhibitor actinomycin D (Act D) attenuated the number of neutrophils accumulating in response to both human and rabbit forms of IL-1 alpha. Local injection of a recombinant human IL-1 receptor antagonist (IL-1Ra) caused a dose-dependent inhibition of local inflammatory responses initiated by human and rabbit IL-1 alpha s well as rabbit IL-1 beta indicating the species cross-reactivity of the antagonist. IL-1Ra was selective for IL-1 in rabbit skin, as responses induced by C5ades Arg and formyl-methionyl-leucyl-phenylalanine (FMLP) were not inhibited. IL-1Ra significantly inhibited the IL-1-induced neutrophil accumulation only when co-injected with the cytokine. The local administration of the antagonist 30 min after rabbit IL-1 alpha failed to inhibit the inflammatory response. These results suggest that the in vivo events leading to the accumulation of neutrophils in response to IL-1 alpha are rapidly initiated. PMID- 1493920 TI - Interleukin-3-induced up-regulation of CR3 expression on human eosinophils is inhibited by dexamethasone. AB - Eosinophil function is regulated by several cytokines, including interleukin-3 (IL-3), IL-5 and granulocyte-macrophage colony-stimulating factor (GM-CSF). Culture of human eosinophils with IL-3 produced a marked, dose-dependent up regulation of CR3 expression. This was maximal after 1 day in culture and dependent on protein and RNA synthesis, as demonstrated by inhibition with cycloheximide and actinomycin D, respectively. IL-5 and GM-CSF had a similar effect on eosinophil complement receptor type 3 (CR3) expression, but the maximal response to IL-5 was always less than to IL-3 or GM-CSF. Dexamethasone inhibited the Il-3-induced up-regulation of CR3 expression in a dose-dependent manner, with an IC50 of 5 x 10(-8) M. This study demonstrates the effect of IL-3, IL-5 and GM CSF on eosinophil CR3 expression and confirms the capacity of eosinophils to modify their phenotype through de novo protein synthesis. This process could be inhibited by physiological concentrations of glucocorticoids, thus providing an additional mechanism for their mode of action in allergic disease. PMID- 1493921 TI - Inhibition of interleukin-5 gene expression by dexamethasone. AB - The effect of glucocorticoids on interleukin-5 (IL-5) gene expression was assessed in human peripheral blood mononuclear cells. IL-5 expression was stimulated by phytohaemagglutinin (PHA), IL-2, phorbol myristate acetate (PMA) or Ionomycin. A semi-quantitative assay for IL-5 gene expression was developed, based on RNA extraction and the polymerase chain reaction. IL-5 expression in response to PHA was profoundly inhibited by 10(-6) M dexamethasone, and significant inhibition was detected at doses of dexamethasone as low as 10(-9) M. When dexamethasone was added to the cells at the same time as PHA, the inhibitory effect could be detected as early as 3 hr. Dexamethasone at 10(-6) M also profoundly inhibited the IL-5 response to PMA and to IL-2, but the IL-5 response to Ionomycin was not significantly affected. These results suggest that dexamethasone may be capable of interfering with a pathway involving protein kinase C. There is increasing evidence that IL-5 may play a pathogenic role in asthma and other manifestations of acute hypersensitivity. The present findings indicate that inhibition of IL-5 expression may be one of the mechanisms whereby glucocorticoids exert their beneficial effects in diseases such as asthma. PMID- 1493922 TI - Characterization of platelet-activating factor synthesized by normal and granulocyte-macrophage colony-stimulating factor-primed human eosinophils. AB - Platelet-activating factor (PAF; 1-alkyl-2-acetyl-sn-glycero-3- phosphocholine) is a mediator involved in the pathogenesis of inflammatory diseases associated with tissue eosinophil infiltration. Previous studies utilizing bioassay or assaying enzymes associated with PAF biosynthesis have suggested that human eosinophils produce PAF. The present study has extended these initial studies by identifying and quantifying the different PAF molecular species and analogues synthesized by human eosinophils in response to A23187 and f-Met-Leu-Phe (FMLP). Gas chromatography-mass spectrometric analysis indicated that A23187-stimulated eosinophils produce at least three molecular species of PAF. The predominant species is 1-hexadecyl-2-acetyl-GPC (16:0) followed by 1-octadecyl-2-acetyl-GPC (18:0) and 1-octadecyl-2-acetyl-GPC (18:1). Eosinophils stimulated with FMLP produce approximately 100-fold smaller quantities of PAF relative to those produced in response to A23187 and only the 16:0 molecular species could be measured. A small percentage (comprising between 2 and 5%) of the 2-acetylated phospholipids produced by eosinophils was the 1-acyl analogue of PAF. Long-term (72 hr) incubation with granulocyte-macrophage colony-stimulating factor (GM-CSF) resulted in a three- to fourfold increase in PAF synthesis from eosinophils stimulated with FMLP, without changes in the profile of PAF molecular species or in the percentage of the 1-acyl analogue of PAF. These data indicate that human eosinophils can produce various molecular species of PAF and that this process can be quantitatively enhanced by GM-CSF. PMID- 1493923 TI - The distribution of immunoreactive interferon-gamma-containing cells in normal human tissues. AB - An immunohistochemical technique has been used to study the distribution of lymphocytes expressing interferon-gamma in normal adult tissues. The greatest concentrations of these cells were seen in mucosal sites exposed to a resident microflora. It is proposed that such organisms, by eliciting immune responses, provide the stimulus for the production of 'physiological' interferon-gamma. This in turn may act to preserve the 'tone' or readiness of the immune system. PMID- 1493924 TI - Signal-dependent pleiotropic regulation of lymphocyte proliferation and cytokine production by 1,25-dihydroxyvitamin D3: potent modulation of the hormonal effects by phorbol esters. AB - The influence of 1,25-dihydroxyvitamin D3 [1,25(OH)2D3] on the proliferation of lymphocytes and on the production of interleukin-6 (IL-6), interleukin-1 beta (IL 1 beta) and interferon-gamma (IFN-gamma) was examined in normal human peripheral blood mononuclear cells (PBMC) activated in vitro either by phytohaemagglutinin (PHA) or by the monoclonal antibody to the T-cell receptor OKT3, or by the combination of each of these two stimuli with phorbol myristate acetate (PMA). 1,25(OH)2D3 inhibited the proliferative response of PBMC to PHA; this effect, however, was abrogated by the addition of PMA (1.6 nM), and it was reversed from inhibition to stimulation by higher concentrations of the phorbol ester. In contrast to the PHA-activated cells, 1,25(OH)2D3 had no effect on the proliferative response of PBMC to OKT3. Further, 1,25(OH)2D3 inhibited the release of IL-6 in cultures of PHA-activated PBMC, whereas it stimulated IL-6 with the addition of PMA in these cultures. In contrast to the PHA-activated cells, 1,25(OH)2D3 increased IL-6 release in OKT3-activated cells. IL-1 beta production was not affected in either PHA- or OKT3-activated cells by the presence of the hormone, but it was stimulated by 1,25(OH)2D3 when PMA was used as a co-stimulus with either PHA or OKT3. Finally, 1,25(OH)2D3 inhibited IFN gamma in both PHA- and OKT3-activated cells, but these effects were attenuated in the presence of PMA. These findings demonstrate that the in vitro effects of 1,25(OH)2D3 on lymphocyte proliferation and cytokine production by PBMC are pleiotropic, and that such pleiotropism depends upon the mode of PBMC activation and presumably the signals that are generated in response to the specific agents used to activate these cells. PMID- 1493925 TI - Immunoregulatory properties of (+)-pentazocine and sigma ligands. AB - (+)-Pentazocine, phencyclidine, and other sigma ligands including 1,3-di-(o) tolylguanidine (DTG), (+)-1-propyl-3-(3-hydroxyphenyl) piperidine [(+)-PPP] and haloperidol were investigated for their potential immunoregulatory properties. High concentrations (10(-5) M) of DTG and haloperidol were found to suppress in vitro murine splenocyte natural killer activity while equivalent concentrations of (+)-pentazocine, (-)-pentazocine and (+)-PPP were without effect. In a reciprocal fashion, lower doses (10(-9) M) of DTG enhanced natural killer activity. Sigma ligands were also found to affect in vitro polyclonal immunoglobulin production following mitogen stimulation. Specifically, high concentrations (10(-6) M) of haloperidol significantly (P < 0.001) suppressed pokeweed mitogen (PWM)-stimulated IgG and IgM production, yet enhanced lipopolysaccharide (LPS)-stimulated IgM production by murine splenocytes. Lower concentrations (10(-8) to 10(-10) M) enhanced (two- to fourfold) PWM-induced IgM production and LPS-stimulated IgG and IgM production. At high concentrations (10( 6)), (+)-pentazocine suppressed (P < 0.01) LPS-induced polyclonal IgG and IgM but enhanced (P < 0.01) PWM-induced IgM production. Both DTG and (-)-pentazocine (10( 8) to 10(-10) M) significantly augmented (two- to threefold) LPS-stimulated murine splenocyte production of polyclonal IgM. Intracellularly, (-)-pentazocine (10(-9) M), haloperidol (10(-7) M), DTG (10(-7) M) and (+)-PPP (10(-5) to 10(-9) M) enhanced forskolin (10(-6) M)-induced cAMP production in splenic lymphocytes while (+)-pentazocine was without effect. Collectively, the data suggest functional and biologically relevant sigma receptors on cells of the immune system. PMID- 1493926 TI - Regulation of macrophage Fc receptor expression and phagocytosis by histidine rich glycoprotein. AB - Regulation of macrophage Fc receptor (Fc gamma R)-mediated phagocytic function by histidine-rich glycoprotein (HRG) was investigated. Pretreatment of oil-elicited inflammatory mouse peritoneal macrophages with HRG for 1-3 hr increased their Fc gamma R-mediated binding and phagocytosis of IgG-opsonized sheep erythrocyte conjugates (EA). A significant reduction of Fc gamma R-dependent EA binding and phagocytosis occurred after pretreatment of macrophages with HRG for more than 8 hr. These results indicate that HRG is capable of modulating Fc gamma R expression in a biphasic fashion, which directly affects the overall efficiency of phagocytosis. HRG differentially regulated the functions of Fc gamma R subclasses. For example, HRG reduced the efficiency of Fc gamma RII (Fc gamma 2b/gamma 1R)-dependent phagocytosis of erythrocytes conjugated with monoclonal IgG2b or IgG1 by macrophages pretreated with HRG for 24 hr. However, when similar studies were performed using erythrocytes coated with monoclonal IgG2a, HRG was less effective in inhibiting Fc gamma RI (Fc gamma 2aR)-dependent phagocytosis. As an HRG-binding glycosaminoglycan, heparin failed to block the regulatory function of HRG on macrophages. Similarly, interferon-gamma (IFN-gamma) was not capable of blocking the functional activity of HRG. These studies suggest that HRG regulates macrophage function via a novel pathway different from that of heparin or IFN-gamma. PMID- 1493927 TI - Constitutive endocytosis and recycling of major histocompatibility complex class II glycoproteins in human B-lymphoblastoid cells. AB - Cleavable cell surface radiolabelling reagents were used to measure the endocytosis and recycling of class II major histocompatibility complex (MHC) glycoproteins in human B-lymphoblastoid cells. It is shown that mature class II alpha beta dimers on the cell surface are constitutively endocytosed and that recycling can be demonstrated even from small endosomal pools. Endocytosis was blocked when cellular ATP levels were depleted or when clathrin polymerization was inhibited, implicating clathrin-coated pits in the endocytic process. Taken together with earlier studies, these results suggest that mature class II MHC molecules are constitutively endocytosed and recycled from acidic peripheral endosomes which may enhance their capacity to bind and present T cell epitopes which do not require processing. PMID- 1493928 TI - Delayed-type hypersensitivity responses regulate collagen deposition in the lung. AB - A previous report showed that hamsters immunized by epicutaneous application of 2,4,6-trinitrochloro-1-benzene (TNCB) were susceptible to the development of pulmonary interstitial fibrosis (PIF) if challenged in the lung with the water soluble form of this hapten 2,4,6-trinitrobenzene sulphonic acid (TNBS). In this study, we investigated the immunological mechanisms that contributed to increased collagen content in the lungs of hapten-immune hamsters after receiving a pulmonary challenge of the sensitizing hapten trinitrophenol (TNP). In order to evaluate the concept that delayed-type hypersensitivity (DTH) reaction modulated their response to TNP in the lung such that it eventuated into PIF, we compared the cutaneous DTH response (48 hr after challenge) with lung collagen deposition (14 days after challenge) in several lines (strains) of hamsters. The inbred LSH strain, was a high responder in the DTH assay to TNP and developed non-resolving PIF in the hapten-immune animals. This is called hapten-immune pulmonary interstitial fibrosis or HIPIF. We also observed that female LSH hamsters were more susceptible to HIPIF induced by TNP than males. On the other hand, age factors influenced DTH and PIF in random-bred LVG hamsters since young hamsters (3 months old) were low responders to TNP and did not develop PIF in the HIPIF model but matured LVG hamsters (retired breeders) possessed DTH reactivity to TNP and subsequently developed PIF. These results suggest that lung collagen deposition in hapten-immune hamster is regulated by T-lymphocyte-mediated immune inflammation (DTH) in the lung and both are dependent on the ability to develop a cutaneous DTH reaction to the hapten. The elucidation of possible mechanisms of DTH-mediated non-granulomatous, non-resolving PIF is important for understanding of the role of environmental chemicals similar in action to haptens in the mediation of skin and lung diseases. PMID- 1493929 TI - Ontogeny and development of extrathymic T cells in mouse liver. AB - We previously demonstrated that the liver may be a major site of extrathymic T cell differentiation in mice. In the present study, the ontogeny and subsequent development of such T cells in the liver and other organs were investigated. This study was possible because these T cells have T-cell receptors (TcR) of intermediate intensity (i.e. intermediate TcR cells) and constitutively express a high level of interleukin-2 receptor beta chain (IL-2R beta). Therefore the two colour staining for CD3 (or alpha beta TcR) and IL-2R beta identifies even a small proportion of intermediate TcR cells. The total numbers of mononuclear cells obtained from the liver, thymus and spleen varied from foetal to adult life. Especially in the liver, many haematopoietic cells were present in the parenchymal space at the foetal stage. There were no lymphocytes in the sinusoidal lumen at this period. In contrast, lymphocytes appeared in the hepatic sinusoids after birth and increased with ageing. Phenotypic analysis revealed that intermediate TcR cells appeared in the liver and spleen on Day 4 after birth. Bright TcR cells of thymic origin were also present in the peripheral organs on Day 4. Thereafter, intermediate TcR cells increased in the liver, whereas bright TcR cells increased in the periphery as a function of age. Similarly, thymectomized and congenitally athymic mice had mainly intermediate TcR cells in the liver and, to some extent, periphery. It is concluded that intermediate TcR cells, possibly of extrathymic origin, are generated only after birth and expand with ageing. PMID- 1493930 TI - Characterization of B-cell phenotypic changes during ileal and jejunal Peyer's patch development in sheep. AB - Changes in B-cell phenotype during development of ileal and jejunal Peyer's patches (PP) of sheep were investigated using flow cytometry and immunoperoxidase stained cryosections. On Day 104 of gestation (term at 150 days) B-cell clusters were identified in the lamina propria of the ileum. These clusters were composed of cells that expressed surface IgM (sIgM), lambda or kappa light chain, and BAQ44A, a B-cell differentiation molecule. No cells in the clusters stained for terminal deoxynucleotide transferase. On Day 132 gestation, a change was evident in the phenotype of ileal PP B cells. Most B cells expressed a reduced level of sIgM and 20% were BAQ44A-. The B cells in the dome region were BAQ44A+ but few BAQ44A+ cells were present in the follicles. At 6-8 weeks of age BAQ44A+ cells were restricted to the dome region of the ileal PP; flow cytometric analysis confirmed that 25% of B cells isolated from the dome/follicle complex were BAQ44A+. Thus, the primordial PP was populated with B cells that were phenotypically similar to circulating B cells (sIgMhigh, BAQ44A+). After 132 days gestation, the predominant B-cell phenotype in the ileal PP changed to sIgMlow and BAQ44A-. This phenotypic change could be the result of either early immigrant B-cell differentiation or subsequent colonization by sIgMlow BAQ44A- B cells. The phenotypic changes of ileal PP follicular B cells were not complete until after birth and different phenotypic changes were observed in follicles of the jejunal PP of young lambs. PMID- 1493931 TI - Quantitative analysis of antigen for the induction of tolerance in carcinoembryonic antigen transgenic mice. AB - In order to analyse the amounts of antigen in the thymus for the induction of tolerance, several carcinoembryonic antigen (CEA) transgenic lines were established which expressed human CEA antigen with different amounts. The chimeric KSN nude mice transplanted with the thymus of the B601 line (in which CEA mRNA and CEA protein could be detected in various tissues) to kidney capsule showed tolerance to human CEA. On the other hand, the chimeric KSN nude mice transplanted with the thymus of the B602 or BC60 line (in which neither CEA mRNA nor CEA protein could be detected by Northern blot analysis and flow cytometry analysis) or normal C57BL/6 (B6) did not develop the tolerance to human CEA. However, the chimeric KSN nude mice transplanted simultaneously with thymus of the B6 and spleen of the B601 line became tolerant to human CEA antigen. In the case of systemic immunization with cells which had CEA antigen, the B601 line was tolerant to human CEA. Surprisingly, the B602 and BC60 lines were also tolerant to CEA molecule. These results indicate that not only the antigen present in the thymus but also the antigen which flows from the peripheral organs to the thymus may be necessary for the induction of CEA tolerance. PMID- 1493932 TI - Class and subclass-associated specificity differences of anti-gliadin antibodies from mucosa and serum. AB - The class and subclass distribution of antibodies against gliadin in intestinal lavage fluid, saliva and serum was investigated in individuals with coeliac disease. Serum antibodies against gliadin were mainly or even exclusively of the IgA1 subclass. In intestinal lavage fluid and saliva, antibodies of both IgA1 and IgA2 subclasses were found. In patients with and without IgA deficiency, an IgG response was detected both in serum and intestinal lavage fluid with a predominance of IgG1 in selected patients. Specific IgG2, IgG3 and IgG4 antibodies were also detected in intestinal lavage fluid, while no specific IgG2, IgG3 or IgG4 antibodies were found in serum, suggesting a local production of specific IgG antibodies. In Western blot analysis, intestinal lavage fluid and serum IgA antibodies reacted against gliadin components with a MW between 33,000 and 42,000. Serum IgA1 antibodies directed against a gliadin component with a MW slightly higher than 42,000 were also observed. Specific IgG and IgM antibodies in both the secretion and serum against gliadin components with a MW between 33,000 and 42,000 were also detected. This study shows that mucosa-derived gliadin-specific IgA and IgG antibodies may be produced even when there is an absence of specific antibodies of the corresponding immunoglobulin subclass in serum. Furthermore, the specificity of serum and intestinal lavage fluid anti gliadin IgA1 antibodies may differ. PMID- 1493933 TI - Hydrocortisone inhibition of human interleukin-4. AB - Glucocorticoids are known to inhibit mitogen-induced proliferation of T cells by suppressing the production of interleukin-2 (IL-2). These hormones have also been shown to inhibit the production of other cytokines, namely IL-1 and interferon gamma (IFN-gamma). It is demonstrated here that hydrocortisone is able to inhibit mitogen-induced production of human IL-4, both at the secreted protein, as well as at the mRNA level. This effect may explain, in part, the immunosuppressive effects of glucocorticoids in the treatment of allergic disease. PMID- 1493934 TI - The concept of dose intensification in the treatment of neoplastic disease. AB - This paper summarizes different theoretical and clinical approaches contributing to the concept of dose intensification. According to this concept, the amount of antineoplastic drug delivered per time predominantly determines the clinical outcome in patients with neoplastic disease. With the availability of recombinant haemopoietic growth factors haematotoxic side effects might be reduced, making this concept more feasible for clinical use. However, more prospective randomized studies, in which dose-intensity is the only treatment variable, are needed to prove that dose intensification will lead to higher survival rates. PMID- 1493935 TI - Treatment of myelodysplastic syndromes (MDS) and high leukaemic risk with low dose cytosine arabinoside (LD-AraC) plus granulocyte-macrophage colony stimulating factor (rh GM-CSF). The EORTC Leukaemia Group. AB - Symptomatic patients with myelodysplastic syndromes (MDS) and 10-30% blasts in the bone marrow were treated with low-dose AraC (2 x 10 mg/m2 subcutaneously (sc) days 1-14) and GM-CSF (fully glycosylated, Sandoz/Schering-Plough, 2 x 150 micrograms protein/day sc) given either subsequently (days 15-21) or simultaneously (days 8-14 and one week rest). Evaluations were carried out after three courses (nine weeks); responding patients could be continued for two further cycles. Eighty-two patients with refractory anaemia and excess of blasts (RAEB), with (RAEBt) or without transformation, were evaluable: 45 RAEB and 37 RAEBt, mean age 64 years (range 17-80 years). A complete remission was achieved in 14 cases (17%), 11 had a good response (13%), and 12 a partial response (15%). Stable disease was found in 21 cases (26%). There were 12 cases of toxic death (15%), progression was noted in eight patients (10%), and death due to disease in three (4%). No difference existed between the two treatment arms with respect to response. Major adverse events during treatment were haemorrhage (25%), infections (23%), and fever with GM-CSF (21%). GM-CSF did not induce leukaemia nor contribute to haemorrhage induced by AraC, but gave rise to an overall response rate of 46% which is high and relatively durable as compared to other treatments in this disease. PMID- 1493936 TI - The side-effect profile of GM-CSF. AB - Granulocyte-macrophage colony-stimulating factor (GM-CSF), a pleiotropic molecule which displays a broad range of haematopoietic activities, has become available for clinical evaluation in various patient groups. It has been shown to be effective in preventing or reversing neutropenia. Adverse effects of GM-CSF, however, are dose related. Appropriate dose, route and schedules for GM-CSF in various clinical settings have recently been defined, the usual range being 5-10 micrograms/kg/day either by 4-6 h intravenous infusion or by subcutaneous injection. At such doses, adverse effects are predominantly mild-to-moderate in nature, occur in 20-30% of patients and usually comprise fever, myalgia, malaise, rash and injection site reaction. Early trials using very high doses of GM-CSF were often associated with marked adverse effects, which in rare cases proved severe (pericarditis and thrombosis). Similarly, a so-called "first-dose reaction", defined as a syndrome of hypoxia and hypotension after the initial but not subsequent doses of GM-CSF, was observed in certain predisposed patients following doses above 10 micrograms/kg/day. Subsequent trials have established that intravenous bolus or short infusions of GM-CSF are more likely to promote adverse effects. Certain patient groups, for example those with myelodysplastic syndrome, acute myeloid leukaemia, inflammatory disease, autoimmune thrombocytopenia or malfunctional immunological responsiveness, require careful clinical monitoring in order to avoid potential complications following the administration of GM-CSF. With the current appropriate administration and doses of GM-CSF, the benefit:risk ratio has been greatly improved. PMID- 1493938 TI - Granulocyte-macrophage colony-stimulation factor and infection. PMID- 1493937 TI - Microbial pathogenicity and host defense in burned patients--the role of inflammatory mediators. PMID- 1493939 TI - Granulocyte-macrophage colony-stimulating factor (GM-CSF): a variety of possible applications in clinical medicine. PMID- 1493941 TI - Granulocyte-macrophage colony-stimulating factor (GM-CSF): what role in bone marrow transplantation? AB - Infection during the period of bone marrow aplasia remains one of the major risks associated with high-dose chemotherapy and transplantation. Over the past several years, a number of investigators in Europe and North America have evaluated the use of GM-CSF in the setting of autologous bone marrow transplantation. These studies have almost all shown a hastening of myeloid engraftment. This, for the most part, has led to fewer serious infections and a decreased hospital stay for the GM-CSF treated patients. An overall survival advantage has not been noted. There has also not been any consistent multi-lineage effect. Future trials with combinations of sequentially used cytokines may lead to more rapid recovery of red blood cells and platelets in addition to granulocytes. PMID- 1493940 TI - The role of GM-CSF in infection. AB - GM-CSF is a hemopoietic growth factor with substantial effects on the proliferation of neutrophils, eosinophils and monocytes/macrophages. Its physiologic role in infection is still poorly understood. The gene for GM-CSF is constitutively transcribed in cells substantial for antiinfectious response. Various cells are activated and induced by TNF and IL-1 to synthesize GM-CSF. No systemic GM-CSF levels can be detected in patients with infection. It is likely that GM-CSF plays its physiological role in the immediate vicinity of the cells by which it is secreted. GM-CSF functionally activates neutrophils, monocytes/macrophages and eosinophils. It may augment T-cell proliferation and function. GM-CSF is effective in mice infected with Staphylococcus aureus or Salmonella typhimurium. Its effect in infectious disease in man should be explored. PMID- 1493943 TI - Depression as a mortality risk factor in hemodialysis patients. PMID- 1493942 TI - The acetate versus bicarbonate dialysis controversy. PMID- 1493944 TI - Increasing plasma phosphorus values by enriching with phosphorus the "acid concentrate" of a bicarbonate-buffered dialysate delivery system. AB - Each of seven hypophosphatemic hemodialysis patients was dialyzed with a phosphorus-enriched, bicarbonate-buffered dialysate. The latter was prepared by the introduction of sodium phosphate salts to the "acid concentrate" of a bicarbonate-buffered dialysate delivery system. The patients tolerated the procedure well and their hypophosphatemia improved. PMID- 1493945 TI - Effects of 1,25 (OH)2D3 treatment on lipid levels in uremic hemodialysis patients. AB - The aim of this study was to evaluate the effect of 1,25 (OH)2D3 treatment on lipid levels in uremic hemodialysis (HD) patients. Thirty-one HD patients who had never been treated with vitamin D nor related drugs and 12 healthy subjects with normal renal functions were studied. Uremic HD patients were randomly divided into two groups. Sixteen uremic HD patients were treated with oral calcitriol (0.5 micrograms/day) for 8 weeks. 13 uremic HD patients and 12 healthy subjects were given placebo. In all these cases before and after 8 weeks of treatments; serum total lipid, total cholesterol, HDL-cholesterol, LDL-cholesterol and triglyceride levels were determined. After calcitriol treatment, triglyceride levels were significantly decreased. But total lipid, cholesterol, HDL cholesterol and LDL-cholesterol levels did not significantly change. In the other two groups there were no significant changes. These results show that calcitriol treatment has a positive effect on triglyceride levels in uremic HD patients. This effect of mechanism of calcitriol treatment has not been known yet. But it could be due to regulation carbohydrates metabolism and normalization of parathormone (PTH) levels. PMID- 1493946 TI - Dietary protein loading and the oral adsorbent AST-120 in the progression of chronic renal failure in the rat. AB - Excess protein intake enhances the progression of renal failure. The oral carbonaceous adsorbent, AST-120, was found experimentally and clinically to retard the progression of renal failure. This study was designed to determine whether deterioration of renal function by dietary protein loading can be prevented or mitigated by this oral adsorbent. Rats with uremia induced by partial renal infarction were fed a normal or high-protein diet for 70 days with or without AST-120, in which the inorganic phosphate content was adjusted to the same level. The survival rate deteriorated with the high dietary protein, but was improved from 30% to 100% with AST-120. Dietary protein loading reduced renal function, based on creatinine clearance. AST-120 improved renal function and renal histopathology not only in the normal diet group but in the high-protein group as well. The progression of renal failure induced by protein loading is thus shown to be prevented by oral AST-120. The mechanism for its action remains to be clarified. PMID- 1493947 TI - Improvement of survival rate in patients with cardiogenic shock by using nonpulsatile and pulsatile ventricular assist device. AB - Between January 1988 and January 1992, 65 patients (pts) had a ventricle assist device (VAD) inserted in our clinic. In 24 pts a VAD was applied because of primarily unsuccessful weaning from cardiopulmonary bypass (Group A). In a further 24 pts (Group B) a VAD was installed for the therapy of refractive cardiogenic shock (CS) after initially successful cardiac surgery (n = 21) and after acute myocardial infarction (n = 3). Twelve pts were bridged to heart transplantation (Group C) and five had a VAD inserted for various other reasons (Group D). In 36 (55.4%) of the total 65 pts a nonpulsatile VAD (Biomedicus 540) was used: 10 in Group A; 20 in B, 3 in C and 3 in D. In 29 pts (44.6%) a pulsatile VAD (Abiomed BVS 5000) was used: 14 in Group A, 4 in B, 9 in C and 2 in D. Weaning rate and long-term survival rates were 50% and 46% respectively in Group A and 38% and 42% in Group B. Seven pts from Group C were transplanted and six are long-term survivors. Two pts (40%) in Group D were discharged from hospital. Major postoperative complications were bleeding (46%), thromboembolism (14%), multiple organ failure (11%), renal failure (11%), arterial embolism (4.6%), sepsis (3%). The results indicate that application of a VAD can be recommended in pts with postcardiotomy CS to allow recovery of cardiac function and in pts with irreversible ventricular damage as bridging to HTX. PMID- 1493948 TI - Extracellular matrix covered biomaterials for human endothelial cell growth. AB - The aim of this study is to optimize conditions for growing endothelial cells on vascular biomaterials. Bovine cornea endothelial cells (BCEC), stimulated by basic Fibroblast Growth Factor (bFGF) secrete an extracellular matrix (ECM) similar to the Descemet membrane produced in vivo by these cells. This ECM, obtained by removing BCEC with an hypotonic shock can be used as a substratum for other endothelial cell growth. Human endothelial cells (HEC) were purified from omentum that was digested with a solution of collagenase-dispase, then filtered through nylon meshes. The cells were further purified by centrifugation onto a Percoll gradient. A comparative study on the attachment and growth of HEC on various coatings (laminin, poly-L-lysine, fibronectin or ECM) indicates that ECM is the most performing substratum. The quality of this endothelium was confirmed by the presence of factor VIII, and MHC class I and the absence of class II antigens. PMID- 1493950 TI - Modelling the optimal control of cyclical leg movements induced by functional electrical stimulation. AB - An optimal control strategy for FES-induced cyclical leg movements in paraplegics is proposed. The control of the cyclical movement of a freely swinging leg is considered as an example. Quadriceps and the flexion withdrawal reflex are stimulated in order to generate a cyclical movement, of which the forward swing resembles the swing phase of gait. Optimal stimulation patterns are determined on the basis of an optimization criterion and a dynamic model of the system. The criterion is based on desired movement parameters and a minimal duration of the stimulation bursts. The movement parameters should ensure the generation of the desired cyclical movement: a desired hip angle range, sufficient foot clearance during the forward swing and knee extension at the beginning of the backward swing. Minimal duration of the stimulation bursts is assumed to yield minimal fatigue. A dynamic model, describing the dynamics of the neural system, the muscles and the leg, was constructed and its parameters identified on the basis of preliminary experiments and literature. Optimal timing of the quadriceps and flexion reflex stimulation bursts was determined by means of computer simulation. These simulations predicted that the flexion reflex should be stimulated in a short burst approximately 150 ms before the start of the forward swing. The quadriceps should be stimulated approximately starting 200 ms before the end of the forward swing in order to ensure knee extension at the beginning of the backward swing. The duration of one cycle of the movement was between 1300 and 1500 ms in these simulations. These results predict that the movement specified by the functional objectives can be realised using only two channels of stimulation. On the basis of the optimal timing, an adaptive control strategy can be designed, which varies the stimulation burst width when muscles fatigue. PMID- 1493949 TI - Peptidyl antithrombogenic agents for extracorporeal blood circulation. AB - The reduction of platelet aggregation and adhesion is essential for preventing thrombus formation during extracorporeal circulation. This report addresses some performances of peptidyl antithrombogenic agents which bind to the adhesive site of fibrinogen. This was based on the recent finding that the sequence of the binding domain of the platelet membrane receptor to fibrinogen was identified as TDVNGDGRHDL (one-letter amino acid code; Thr-Asp-Val-Asn-Gly-Asp-Gly-Arg-His-Asp Leu), entitled B12. The addition of B12 and shorter-chain analogue peptides dose dependently suppressed platelet aggregation and adhesion onto a fibrinogen-coated surface. The shorter the amino acid sequence, the less effective was inhibition. The inhibitory effect on platelet adhesion in vivo was significant under continuous infusion of B12. These inhibitory effects were compared with those by a receptor-binding RGD (Arg-Gly-Asp) peptide, which is the common active site to adhesive proteins. PMID- 1493951 TI - Therapeutic community treatment for personality disordered adults: changes in neurotic symptomatology on follow-up. AB - Personality disordered patients are important as they place high continuing demands on services and are often refractory to traditional treatments. Often personality disorders may co-exist with neurotic symptomatology, worsening prognosis of the latter. This paper reports change in neurotic symptomatology following intensive, long term, therapeutic community treatment for such patients. Sixty two subjects with personality disorder were followed up for eight months after discharge (response rate 65%). Results showed a highly significant reduction in symptomatic distress as measured by the SCL-90R questionnaire. Investigation of the reliability and clinical importance of the change in individual subjects demonstrated that 55% of subjects had improved reliably, and in 32% this change was also clinically significant, whilst only 6.5% of subjects had deteriorated reliably. PMID- 1493952 TI - Japanese Type A behavior pattern is associated with "typus melancholicus": a study from the sociocultural viewpoint. AB - An examination of the relationship between Type A behavior pattern (TABP) and "Typus Melancholicus" (TM) in 212 coronary heart disease (CHD) patients in Japan revealed that: CHD patients with TABP were significantly more likely to have a depression-prone personality, what Tellenbach calls "Typus Melancholicus"; this tendency was observed not only in CHD patients but also among healthy Type A subjects; and TM is positively correlated with Type A. The results of our studies from a comparative sociocultural viewpoint indicate that TM may be involved in Japanese TABP, suggesting the possibility that driving, self-sacrificing and obsessional traits are related to Type A behavior in a variety of different cultural contexts. PMID- 1493954 TI - Letters to the Rebbe. Millenium, messianism and medicine among the Lubavitch of Stamford Hill, London. AB - The Lubavitch are a group of Hasidic Jews living in Stamford Hill, London N16. After a description of their lifestyle and the importance of the Rebbe in the community, this paper examines their concepts of the body, health and healing based on Kabbalistic teachings. For this group healing involves both control of sickness and the correction of spiritual disorder associated with it: the Rebbe plays a key role in the latter. The paper ends by discussing the extent to which conversion of religious groups results in any form of healing. (See Glossary for translation of Jewish words.) PMID- 1493953 TI - Perceived self in educated employed and educated unemployed women. AB - The purpose of this study was to compare the perceived self-concept of employed and unemployed educated women. The study also examined the relationship of perceived self-concept with the type of employment and period of service of the employed women. The sample consisted of 150 employed and 150 unemployed educated married women residing in an urban area of Patna. The self-concept scale of Deo (1985) was used in the study. The findings showed that the perceived self of the employed women scored relatively higher in each of the five attributes of the perceived self; ie. Aesthetic, Emotional, Character, Intellectual and Social. It was concluded, from this study, that employment leads to a higher self-concept among educated women, which however varied with different types of employment. PMID- 1493955 TI - Nurses' views of parasuicide in a developing country. AB - This study examines the knowledge, beliefs, attitudes, intentions and experiences of nurses at various stages of their careers with regard to patients who have made suicide attempts. It focuses particularly on the relationship of traditional Shona beliefs about suicide and considers how they interact with western medical beliefs. A detailed questionnaire covering these elements was administered to three groups of nurses. They were sampled at either the beginning or end of their training or after approximately ten years experience. Knowledge of suicide was found to be poor and attitudes towards parasuicide were negative. Traditional beliefs were held strongly by all groups of nurses; western beliefs were strongest amongst experienced nurses. Practical implications of these attitudes and beliefs for training are considered. PMID- 1493956 TI - Opinions about and reactions to suicide, and the social acceptance of a suicidal classmate among Turkish high school students. AB - The present study investigated the opinions about suicide and reactions to a suicidal peer among 89 female and 78 male Turkish high school students. Females more than males believed that suicide should be discussed among friends. More males than females perceived suicidal persons to be mentally ill and to be punished in the other world. Females showed greater acceptance for a suicidal classmate than males. An attitude for openly discussing suicide was associated with higher acceptance of a suicidal classmate. Perceiving suicidal individuals to be mentally ill was associated with lower acceptance of a suicidal peer. PMID- 1493957 TI - Psychiatric morbidity of foreign students in Yugoslavia: a 25 year retrospective analysis. AB - Psychiatric morbidity of hospitalized foreign students in Yugoslavia was analyzed in a 25-year retrospective study and was compared to the psychiatric morbidity of a group of Yugoslav students hospitalized in the same psychiatric institutions, over the same time period. Results showed significantly higher rates of paranoid and depressive reactions amongst foreign students, and suggested correlation between their psychiatric morbidity and maladaptation to the new living conditions. PMID- 1493958 TI - Factors related to psychiatric hospitalisation for first contact patients. AB - In a consecutive series of 178 first contact patients hospitalisation was significantly related to greater distance travelled, low income, acute onset, short duration, past history of illness and history of substance abuse compared to those receiving outpatient disposition. Hospitalised manics and paranoid schizophrenics had higher BPRS scores while hospitalised non-paranoid schizophrenics had lower scores. There was a significant positive correlation between hospitalisation and BPRS items: grandiosity, excitement, elated mood, motor-hyperactivity and distractibility and negative correlation with somatic concern, anxiety, depressive mood and social incompetence. Stepwise multiple regression analysis found the combination of loss of functioning, social incompetence and grandiosity to best predict disposition decision. PMID- 1493959 TI - Non-attendances at a marital and sexual difficulties clinic: a controlled intervention study. AB - Clients referred to a marital and sexual difficulties clinic were given an information sheet and a questionnaire in a controlled study. This led to a significant reduction in non-attendance at the assessment interview (p < 0.01) and in a significantly higher number of clients attending for therapy (p < 0.05). PMID- 1493960 TI - Stealing in bulimia nervosa. AB - This clinical study examines the prevalence of stealing and the personal and behavioural factors which distinguish stealing and non-stealing behaviour in a population of 312 female normal-weight bulimics. Bulimic patients who stole had poorer early interpersonal relationships, earlier onset of sexual feelings with greater subsequent sexual activity and increased illicit drug use. The suggestion is made that stealing is a marker of severity. In addition, bulimics who stole appeared to exhibit more obsessional qualities with increased ritualisation. PMID- 1493961 TI - The impact of the economy on suicide and homicide rates in Japan and the United States. AB - A time series study of socioeconomic correlates of suicide and homicide in Japan and the USA from 1953 to 1982 revealed cross-national differences. Divorce rates were positively associated with rates of personal violence in the USA but negatively associated with these rates in Japan. Unemployment and female labor force participation also correlated differently with rates of personal violence in the two nations suggesting that different theories may be necessary to account for the variation in rates of personal violence in different societies. PMID- 1493962 TI - The interpersonal aspect of the decision making process in the psychiatric emergency room. PMID- 1493963 TI - [Current understanding of mucociliary transport]. AB - This review article deals with current understanding of mucociliary transport and its significance for clinical practice. The ultrastructure of cilia and principles of mucociliary clearance in the upper respiratory tract are outlined. Practicable diagnostic measures described are the saccharine test, vital cytological sampling of the nasal mucosa and electron microscopy for ultrastructural studies. Special pathologies such as the immotile cilia syndrome and mucoviscidosis are outlined in their relation to mucociliary transport. Recommendations are given as to how mucociliary transport might be influenced therapeutically. PMID- 1493964 TI - [Diagnostic aspects of isolated sphenoid sinusitis]. AB - The clinical occurrence of isolated sphenoid sinusitis is rare. Due to a long history and few initial symptoms, diagnosis of this potentially fatal infections can be difficult. Radiological aspects in 10 patients are presented (e.g. type and design of examination and whether inflammatory or destructive changes could be shown), as well as clinical aspects (cranial nerve palsy, concurrent inflammation, duration of disease and therapy). CT proved to be superior in diagnosing the extent of any bony changes, while MRI was more useful in detecting inflammation. PMID- 1493965 TI - [Holmium:YAG laser surgery. Possibilities for use in inflammatory paranasal sinus diseases]. AB - A pulsed Holmium: YAG laser (lambda = 2120 nm) was used during functional endoscopic endonasal surgery in ten patients with recurrent chronic inflammation of the paranasal sinuses. The Holmium: YAG laser energy was coupled to a 600 microns core diameter nylon fiber. Power settings of 950 mJ per 2.5 microseconds pulse at 5 pulses per second were used. Tissue responses to treatment were examined by light microscopy. The photoablative mechanism of the laser-tissue interaction led to bone and soft tissue ablation with only a minor thermal component in the target zone. In comparison with other laser types available clinically, there was no carbonization zone after use of the Holmium-YAG laser. The area of tissue damage produced was significantly smaller (370-520 microns only) and wound healing proceeded without complication. The physical settings of the laser equipment are described with regard to their significance in photoablation when using flexible light-conducting fibers. The possible role of the Holmium: YAG laser in clinical surgery is discussed on the basis of the present experience. PMID- 1493966 TI - [Decreased aspiration after extensive tumor surgical interventions in the area of the mouth cavity and pharynx by laryngeal suspension]. AB - Lateral laryngeal suspension in combination with a cricopharyngeal myotomy represents a simple technique for prevention and/or treatment of chronic aspiration in patients during or after surgery for head and neck cancer. At the Department of Otolaryngology/Head and Neck Surgery of the University of Heidelberg this technique has been employed with satisfying results in 6 patients with large carcinomas of the oral cavity and pharynx. Lateral laryngeal suspension was not able to prevent--or if used secondarily--to eliminate aspiration completely in all patients. However, none of our patients experienced aspiration of saliva postoperatively. All were able to use a speech canula and some could even be fed orally. PMID- 1493967 TI - [Immunohistochemical findings in otosclerotic lesions]. AB - Despite numerous scientific efforts, the etiology of otosclerosis still remains unknown. Pathogenically, there are several signs of a chronic inflammatory process of the bony otic capsule. In this study, we tried to characterize the components of chronic inflammation by immunohistochemical techniques. Within otosclerotic lesions a mixed cellular infiltrate can be observed, consisting of lymphocytes, macrophages and plasma cells. Macrophages which are capable of presenting antigen in association with major histocompatibility antigens (MHC) class I and class II to CD8(+)-, and CD4(+)-T cells, respectively, were found in otosclerotic lesions based on their expression of the MAC387 antigen. Furthermore, HLA-DR positive cells and complement C3 have been found in resorption lacunae of otosclerotic lesions. Several osteoblasts and chondrocytes in active otosclerotic lesions reveal a strong surface expression of beta-2 microglobulin, indicating an increased MHC class I antigen expression in active otosclerotic lesions. In agreement with recently published data we found that a large fraction of the lymphoid cells are antigen-primed T-cells expressing an alpha/beta T-cell receptor in association with CD3 molecules on their surfaces. CD4+ lymphocytes which functionally represent lymphokine-secreting cells are activated through the specific recognition of antigen, presented in context with MHC class II molecules such as HLA-DR. Therefore, the presence of MHC class II positive cells are crucial for the initiation of a local immune response. Thus, our observation of HLA-DR positive cells in otosclerotic lesions is of particular interest.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1493969 TI - [Evaluation of frequency selectivity from psychoacoustic tuning curves]. AB - Psychoacoustic tuning curves (PTC) can be regarded as filter curves, whereas their forms represent hair cell activity. Different influences--for example, noise, toxins, pharmacological causes and age--can change the PTC as a consequence of changed frequency selectivity without indication of deterioration in the audiogram. The objective of this investigation was to determine the visually perceivable change in the PTC as a quantifiable result. In so doing, the PTC was transformed into a hyperbola characterized by a parameter Q5. An example demonstrates the temporal change of Q5 under the influence of pharmacological drugs. PMID- 1493968 TI - [Correlation between electrically-induced stapedius reflex and discomfort threshold in cochlear implant patients]. AB - Electrically elicited stapedius reflex thresholds are an objective criteria for the fitting of speech processors in very young children. Reflex thresholds generally fit well within the upper third of a subject's individual dynamic range, the difference between electrical threshold of hearing, (T) and maximum comfort (C) levels and can be used to predict ultimate behavioral maximum comfort levels. In acoustically elicited stapedius reflexes a saturation of impedance amplitude can be registered at approximately 110 dB, which is 90% of the dynamic range. Assuming a similar relationship for the electrically elicited stapedius reflex there would be two values within the dynamic range which could be used for extrapolation of the threshold level. In the present study, the electrically elicited stapedius reflex was examined in 16 deaf patients who had received 22 channel Clark/NUCLEUS cochlear implants. Using an apical, a medial and a basal electrode pair, different stimulation positions within the cochlea were tested. The contralateral reflexes could be elicited in 11 patients (69%). A saturation of the reflex amplitude was recordable in 10 subjects, at least in one of the electrode pairs. The reflex saturation in all cases was located close to the uncomfortable loudness level within the subjects' dynamic ranges (at 95% dynamic). This finding is comparable to acoustic matter. As a result, these data together with reflex threshold data suggest a means for predicting to predict the threshold levels. PMID- 1493970 TI - [Long-term manifestations of laryngeal sarcoidosis]. AB - We report the medical history of a 19 year old female patient with isolated laryngeal sarcoidosis, who was followed for 12 years. It illustrates the typical course of the disease with remissions and relapses until the inflammation is "burnt out." Although the laryngoscopic findings of pale-red swollen supraglottic structures are pathognomonic, diagnosis is rarely assumed at first sight. Long term administration of cortisone in low dosage is the treatment of choice. Acute exacerbations with increasing airway obstruction may occur at any time, although in general a tracheotomy can be avoided because high-dose cortisone is highly effective. Over the years, the granulomatous character of the inflammation turns into a chronic non-specific one, while the laryngoscopic aspect hardly changed. Once the sarcoidosis is burnt out, the danger of an acute exacerbation diminishes. PMID- 1493971 TI - [Cervical lymph node metastasis as a primary manifestation of esthesioneuroblastoma]. AB - A 51-year-old male patient presented with right-sided swelling of the neck and a 2-year history of decreasing olfaction that had culminated in complete anosmia. CT and MRI showed a calcified ethmoid tumor and destruction of the lamina cribrosa extending into the anterior fossa and frontal lobes. Contrast material demonstrated marked enhancement on the CT and MRI. Bilateral angiography of the external and internal carotid arteries failed to show tumor vascularity typical for an esthesioneuroblastoma but rendered an olfactory meningioma unlikely. Histological findings of cervical lymph nodes removed during neck dissection showed infiltration by an esthesioneuroblastoma (Kadish C classification). Tumor calcifications in these neoplasms are generally well seen on CT and--while not specific--may suggest the diagnosis. CT and MRI are the most sensitive methods of demonstrating local tumor growth, metastasis and bone destruction. PMID- 1493972 TI - [Cicatricial mucous membrane pemphigoid with laryngeal involvement. Case report and review of the literature]. AB - Benign mucous membrane pemphigoid (BMMP) is characterized by immunoglobulin deposits along the basal zone of the skin and mucous membranes, leading to blistering erosions of the involved regions. We report the case history of a 72 year old woman, in whom a cicatricial, supraglottic stenosis caused increasing dyspnea. Through immunohistochemical analysis the diagnosis of BMMP was confirmed. Therapy with cyclophosphamide and steroids led to a remission. Clinical, diagnostic and therapeutic aspects of this laryngologic-dermatologic disease are presented and discussed in the context of the available literature. PMID- 1493973 TI - [Initial manifestation of localized myasthenia gravis as a differential diagnosis to foramen jugulare syndrome]. AB - The jugular foramen syndrome results in pareses of cranial nerves IX, X and XI and is usually caused by localized pathology of the skull base and/or brainstem through tumors or rheological disorders. As demonstrated in the case reported a systemic neurological illness such as myasthenia gravis should be considered if MRI, CT scan and DSA show no pathology. PMID- 1493974 TI - Giardia comes of age: progress in epidemiology, immunology and chemotherapy. PMID- 1493975 TI - Optimal dosage of beta-lactam antibiotics: time above the MIC and inoculum effect. PMID- 1493976 TI - Antimalarial drug resistance: the pace quickens. PMID- 1493977 TI - Biochemical basis of mupirocin resistance in strains of Staphylococcus aureus. AB - Twenty one strains of Staphylococcus aureus, of varying resistance to mupirocin, were examined in order to determine the mechanism of resistance to this antibiotic; six of these strains were mupirocin sensitive (MIC 0.12-1.0 mg/L) nine moderately resistant strains (MIC 8-256 mg/L) and six highly resistant strains (MIC > 2048 mg/L). Mupirocin showed a time-dependent inhibition of the target enzyme, isoleucyl-tRNA synthetase (IRS); incubation of the antibiotic with this enzyme before adding the substrates markedly increased inhibition in sensitive strains. The IRS I50 values (the antibiotic concentrations which cause a 50% decrease in enzyme activity) correlated well with the MIC values for each strain (P < 0.01). The mean I50 value for sensitive strains was 3.3 x 10(-2) mg/L, in moderately resistant strains it was 1.3 x 10(-1) mg/L and in highly resistant strains it was 7.5 mg/L. No degradation of mupirocin could be detected during extended incubation of the antibiotic with cell free extracts from four resistant S. aureus strains. We conclude that the production of a modified IRS enzyme is the major cause of mupirocin resistance in the strains studied. PMID- 1493978 TI - The influence of salt concentration on the detection of methicillin resistance in coagulase-negative staphylococci. AB - The detection of methicillin resistance by the breakpoint method was examined using three different media containing varying quantities of added salt and 4 mg/L methicillin or 1 mg/L oxacillin. Three hundred clinical isolates of eight species of coagulase-negative staphylococci were tested. In 68 strains methicillin resistance was expressed only at certain salt concentrations and four distinct susceptibility phenotypes were observed. A correlation between the susceptibility phenotype and the species of the isolate was found. Testing on Columbia agar (CA) containing 4 mg/L methicillin with 0% and 4% added salt was required to detect resistance in all 68 strains. Resistance was detected less frequently using Balanced Sensitivity Test (BST) agar or Diagnostic Sensitivity Test (DST) agar containing methicillin or CA, BST or DST agar containing oxacillin. Increased production of beta-lactamase was shown to be an unlikely cause of MR in these strains. Disc sensitivity tests were performed on the 68 strains using five different media. Columbia agar gave optimum results as the other media gave enhanced zones of inhibition for some isolates. Further tests were performed on CA containing varying salt concentrations using both oxacillin and methicillin discs. A close relationship between the staphylococcal species, and the influence of increasing salt concentration on zone size was found. Discrepancies were noted between results obtained by breakpoint and the results obtained with methicillin discs particularly with Staphylococcus simulans and some Staphylococcus epidermidis strains. Results obtained with oxacillin discs more closely correlated with those obtained by breakpoint, but only when disc tests were performed on media with low and high salt content. To identify methicillin resistance in strains of CNS by disc tests, the use of Columbia agar with 0% and 5% added salt and oxacillin discs is recommended. PMID- 1493979 TI - 2-Heptyl-4-hydroxyquinoline N-oxide, an antistaphylococcal agent produced by Pseudomonas aeruginosa. AB - Clinical isolates of Pseudomonas aeruginosa produce low molecular weight, hydrophobic substances which inhibit the growth of Staphylococcus aureus and other Gram-positive organisms. The active substances have been purified from a culture of P. aeruginosa and characterized as a mixture of 2-heptyl-4 hydroxyquinoline N-oxide and its homologues. The alkyl-hydroxyquinolines (derived through reduction of the N-oxide) were also produced by P. aeruginosa cultures but, in general, were less active against S. aureus. 2-Heptyl-4-hydroxyquinoline was identified in a sample of human bronchial secretions from a patient with cystic fibrosis who was heavily colonized with P. aeruginosa. Production of antibacterial alkyl-hydroxyquinoline N-oxides in human lung may explain the observation that the presence of P. aeruginosa in the sputum of patients with cystic fibrosis is correlated with the absence of S. aureus. PMID- 1493980 TI - Comparative in-vitro activities of newer cephalosporins cefclidin, cefepime, and cefpirome against ceftazidime- or imipenem-resistant Pseudomonas aeruginosa. AB - Three hundred and thirty-four recent clinical isolates of Pseudomonas aeruginosa were examined for susceptibility to cefclidin, cefepime, and cefpirome. Of these strains, 28.7% were resistant to ceftazidime, and 23.4% were resistant to imipenem. About half of those resistant to ceftazidime were also resistant to imipemem. Although 37.4% and 59.6% of the isolates were resistant to cefepime and cefpirome respectively, and most or all ceftazidime-resistant strains showed resistance to cefepime and cefpirome, only 3.9% were resistant to cefclidin. Ceftazidime-resistant, but cefclidin-susceptible, P. aeruginosa produced high levels of chromosomal cephalosporinases. Of the compounds tested, cefclidin showed the lowest affinity for these enzymes, suggesting that its high activity against P. aeruginosa resistant to several beta-lactams was mainly due to its high resistance to enzymatic hydrolysis. Thirteen strains resistant to cefclidin were also resistant to both cefepime and cefpirome, and eight and three of these strains were resistant to ceftazidime and imipenem, respectively. A penicillinase, which hydrolyzed cefclidin, was detected in the cefclidin resistant P. aeruginosa, which was similar to the OXA-1 beta-lactamase. PMID- 1493981 TI - The in-vitro bactericidal activities of combinations of antimicrobial agents against clinical isolates of Mycobacterium avium-intracellulare. AB - The in-vitro activities of five antimicrobial agents (rifabutin, clarithromycin, ethambutol, ciprofloxacin and amikacin), alone and in combination, were evaluated against 21 strains of Mycobacterium avium-intracellulare isolated from patients with AIDS. The combined activities of these agents were studied on solid medium by a full chequerboard method. Synergy was demonstrated most frequently (28-71% of isolates) with those combinations that included ethambutol. In killing curve experiments where double and triple combinations of agents were tested against two of the strains, 99% kill was achieved in seven days at concentrations well below those that are attainable in serum. However, an additive rather than a synergic effect was seen in most instances. Although ciprofloxacin alone had the greatest bactericidal activity against these two strains, its activity was antagonized in the presence of rifabutin; this antagonism became inapparent when a third agent was added. Demonstration of bactericidal activity in broth culture may be more relevant than the results of susceptibility testing on solid medium when choosing antimicrobial therapy for patients with this infection. PMID- 1493982 TI - High-level aminoglycoside resistance among enterococci and group A streptococci. AB - The occurrence of high-level aminoglycoside resistance (HLAmR) was determined for 73 enterococci and 54 group A streptococci by the high-load disc method, tube macrodilution and the polymerase chain reaction (PCR). The PCR method revealed the presence of genes coding for aminoglycoside-3'-O-phosphoryltransferase-III (APH(3')-III), aminoglycoside-6'-N-acetyltransferase/2''-O-phosphoryltransferase (AAC(6')/APH(2'')), or both, in 20.6%, 9.6% and 4.1% of the enterococci, respectively. The prevalence of HLAmR to at least one aminoglycoside among local enterococci was 37% (27/73). Only one of 54 Streptococcus pyogenes isolates produced APH(3')-III and exhibited high-level resistance to kanamycin and streptomycin. In general, the three methods yielded comparable results, with only three discrepancies among the 127 isolates examined. High-load disc screening and tube macrodilution proved to be practical, reliable and reproducible, and thus suitable for routine screening. Of 20 Enterococcus faecalis strains tested, all were penicillin-tolerant. Only one of seven penicillin-tolerant S. pyogenes strains was HLAmR. No association between the two forms of resistance was found. PMID- 1493983 TI - Prevalence of resistance to beta-lactam antibiotics in Escherichia coli isolated from blood from 1969-1991. AB - MICs of beta-lactam antibiotics were determined for blood culture isolates of Escherichia coli from patients in St. Thomas' Hospital, London between 1969 and 1991. There was correlation between MICs of carbenicillin and those of amoxycillin (Kendall's coefficient of rank correlation, tau = 0.67), mezlocillin (tau = 0.73), cephaloridine (tau = 0.64) and amoxycillin/clavulanic acid (tau = 0.72), but less correlation between MICs of carbenicillin and cefuroxime (tau = 0.31). During the two decades, the geometric mean MICs increased for carbenicillin (6.6-fold increase in mean MIC), mezlocillin (3.4-fold increase in mean MIC), cephaloridine (two-fold increase in mean MIC) and, to a smaller extent, amoxycillin/clavulanic acid (1.2-fold increase in mean MIC), but not for cefuroxime. These changes were the result of increases in the proportion of isolates that were resistant to carbenicillin and not of changes in the phenotype of carbenicillin-resistant isolates. PMID- 1493984 TI - Co-trimoxazole impairs colonization resistance in healthy volunteers. AB - The influence of co-trimoxazole on colonization resistance of the bowel was investigated in six healthy volunteers, by measuring the numbers of indigenous aerobic flora and of a co-trimoxazole resistant challenge strain of Klebsiella pneumoniae. Impairment of colonization resistance of the bowel was shown by a significant increase in the numbers of yeasts in the faeces of five of six volunteers, by a significant increase in the numbers of Gram-negative bacilli in the faeces of two of six volunteers, and by facilitation of colonization of the bowel by the challenge strain in all volunteers. Impairment of colonization resistance of the mouth was shown by the development of glossitis caused by Candida albicans in two volunteers, and by a significant increase in the numbers of yeasts in mouth washings from four volunteers. It is concluded that co trimoxazole impairs colonization resistance of the gastro-intestinal tract. PMID- 1493985 TI - Ecological effects of short-term ciprofloxacin treatment of travellers' diarrhoea. AB - Forty-two subjects travelling to Mexico for 11 days were enrolled in a randomized, double-blind, placebo-controlled trial comparing ciprofloxacin 250 mg twice daily for three days or placebo for treatment of travellers' diarrhoea. Seventeen (41%) subjects were randomized to treatment. By the last treatment day, all seven evaluable subjects in the ciprofloxacin group, and three of eight evaluable subjects in the placebo group were cured (P = 0.04). The mean time to cure was 26 h for ciprofloxacin and 60 h for placebo-treated patients (P = 0.03). Faecal specimen were collected pre-travel, after four days in Mexico, 48 h post travel and four weeks post-travel. Potentially pathogenic Escherichia coli strains carrying diarrhoeagenic virulence genes were detected by DNA hybridization tests, during or after travel, in 41% of treated and 31% of asymptomatic travellers. Travel, irrespective of diarrhoea and type of treatment, had a minor impact on the aerobic and anaerobic microflora. In travellers with ongoing diarrhoea, a suppression of the numbers of anaerobic bacteria was found, but the microflora was otherwise virtually unaffected. Significantly increased frequencies of E. coli resistant to ampicillin, doxycycline, chloramphenicol and co-trimoxazole were found during and after travel in all categories of travellers, though more frequently in subjects who experienced diarrhoea. The susceptibility of Bacteroides spp. remained unchanged. The sensitivity of E. coli to ciprofloxacin was not affected by travel, except in four ciprofloxacin-treated subjects who acquired multiresistant E. coli with ciprofloxacin MICs of > or = 0.125 mg/L post-travel. Bacteroides strains with MICs of > or = 64 mg/L were isolated post-travel from four ciprofloxacin-treated patients, and from one of the other 34 travellers not treated with ciprofloxacin. PMID- 1493986 TI - Randomized prospective study comparing two dosage regimens of ciprofloxacin for the treatment of typhoid fever. AB - Sixty-two patients with blood culture-proven typhoid fever were randomly assigned to receive either 500 or 750 mg of ciprofloxacin orally, twice daily for 7 days or for two days following defervescence, whichever was greater. Thirty-four and 28 patients received 500 mg and 750 mg respectively. Strains of Salmonella typhi resistant to ampicillin, chloramphenicol and co-trimoxazole were isolated from the blood of 27 patients (43.5%). No resistance to ciprofloxacin was encountered. Both regimens were equally effective; fever subsided in mean times of 4.9 +/- 1.7 days in the 500 mg group and 5.2 +/- 2.2 days in the 750 mg group (P = 0.54). All patients were cured, although one patient in the 750 mg group experienced a presumed relapse two months following completion of therapy. Ciprofloxacin administered for 7-10 days was adequate treatment for 57 of the 62 patients (92%); only five patients required therapy for more than 10 days. Patients with pretreatment symptoms of > or = 10 days duration defervesced in a mean of 5.7 +/- 2.3 days compared with 4.5 +/- 1.3 days (P = 0.01) for those with symptoms of shorter duration. We conclude that 500 mg of ciprofloxacin taken orally twice daily is adequate treatment for typhoid fever. PMID- 1493987 TI - Describing and comparing in-vitro antimicrobial activity by the box-plot technique. PMID- 1493988 TI - Bioassay for glycopeptides. PMID- 1493989 TI - Characterization of imipenem-resistant Pseudomonas aeruginosa strains from cystic fibrosis patients. PMID- 1493990 TI - Optimizing antimicrobial therapy. A method for antimicrobial drug use evaluation. PMID- 1493991 TI - Susceptibility of Streptococcus pneumoniae to five antibiotics. PMID- 1493992 TI - Septicaemia due to a new species of Rhodococcus that contaminated closed system packed red blood cells--cure with imipenem monotherapy. PMID- 1493993 TI - Superinfections by Escherichia coli resistant to fluoroquinolones in immunocompromised patients. PMID- 1493994 TI - Human skin disposition of cefpodoxime after oral administration of its proxetil ester. PMID- 1493995 TI - The treatment of a large outbreak of acute bacterial gastroenteritis with ciprofloxacin. PMID- 1493996 TI - Relationship between cariogenic events and salivary tests in boys and girls: oral examination. AB - For boys and girls several salivary tests have been correlated with the following early cariogenic processes developing simultaneously in dental enamel: initiation, regression, stabilization and progression. These events were observed clinically during three consecutive intervals. Only correlations, significant during at least two random intervals were discussed. The Snyder test determined at 24 hours was significantly positively correlated with most events confined to the enamel surfaces and only the Snyder test determined at 48 hours in stimulated saliva appeared to be significantly positively related with deeper processes such as progression. In addition, the mineral composition of Ca2+, P and Mg2+ in saliva was significantly related to cariogenic events in the enamel surfaces of girls, and its viscosity for boys. Finally, and most interesting from a clinical point of view, was the fact that caries progression was negatively related with P concentrations in both unstimulated and stimulated saliva for girls. For boys a negative correlation was found between caries progression and flow of stimulated saliva. PMID- 1493997 TI - The effects of NaF, alpha-C12DMEAHF and alpha-C12DMEAHCl on caries development in dentine in situ. AB - Using histological techniques it was possible to demonstrate that during in situ caries development in bovine dentine, the demineralization process preceded the emergence and changes in the organic matrices. In addition, these data demonstrated as that 0.006% F- given either as the quaternary ammonium compound or NaF completely prevented demineralization by acting primarily on the dentine mineral. Inhibition by the quaternary ammonium compound alone was incomplete probably through repression of acid production by micro-organisms normally resident in the saliva. PMID- 1493998 TI - [The adhesion of Actinobacillus actinomycetemcomitans to oral epithelial cells]. AB - Adherence is a major pathogenicity factor for many bacteria. The aim of this study was to measure the adherence potential of Actinobacillus actinomycetemcomitans (A.a.) for buccal epithelial cells (BEC). In the second part of the study, the inhibitory potential of saliva on adherence between A.a. and BEC was tested. Saliva specimens were obtained from three groups of subjects: a group of normal subjects (NS), a group of subject with localized juvenile periodontitis (LJPS) and a group of subjects with adult periodontitis (APS). Clinical strains of A.a. showed a major adherence potential for BEC (25.5 A.a./BEC). In contrast, reference strains of bacteria appeared to possess a much lower potential for adherence (12.6 A.a./BEC). Saliva samples taken from from the LJPS and APS group had a high inhibitory adherence potential, since in each of these groups a reduction of 60.9% and 66.7% respectively, was observed in the number of bacteria adhering to BEC. PMID- 1494000 TI - Applications of chromatography and electrophoresis in food science. PMID- 1493999 TI - Acid resistance of human enamel by brushing with and without abrasive dentifrice. AB - Daily brushing with and without abrasive dentifrice pieces of was performed on the ground surfaces of human enamel attached to resin plates which were exposed to the oral cavities of 4 subjects for 8 weeks. The difference in acid resistance between a pair of enamel pieces obtained from the same tooth was examined with atomic absorption spectrometry. After etching with a lactate buffer solution at pH 4.5, the amount of Ca dissolved from the enamel in each pair by brushing without dentifrice was significantly lower than that when brushing with an by abrasive paste. Under SEM, the brushing with paste caused prism structures to appear clearly on the enamel surface, while brushing without dentifrice caused a nonbacterial organic film, i.e., salivary pellicle, to cover the surface. These results indicate that the pellicle is protected by mineral deposits when brushing without dentifrice but brushing with an abrasive paste tears off the unmineralized pellicle. Brushing without dentifrice induces a stronger resistance to acid on the enamel surface. PMID- 1494001 TI - Chromatographic determination of vitamins in foods. AB - Chromatographic methods for the determination of water- and fat-soluble vitamins in foods are reviewed. For each vitamin, sample preparation, detection problems and chromatographic conditions are presented and discussed. High-performance liquid chromatography (HPLC) is becoming a standard method in vitamin assay, especially for routine work. HPLC systems can be automated using in-line solid phase extraction and column switchings, resulting in very sensitive methods, even when simple UV detection is employed. PMID- 1494002 TI - Advances in planar chromatography for the separation of food lipids. AB - A survey of the advances in planar chromatography for the separation of food lipids is presented. Techniques of planar chromatography [densitometry, preparative thin-layer chromatography (TLC) and TLC with flame ionization detection, etc.] together with applications from the areas of dairy, marine and plant lipids are discussed. Additives such as lecithins (emulsifying agents) are also considered. PMID- 1494003 TI - Chromatographic analysis of antibiotic materials in food. AB - The monitoring of food materials for antibiotic residues is an area of increasing concern and importance due to the potential impact on human health. Large-scale screening applications require methods that are rapid, accurate, provide low detection limits and are free from interference. The problem is further complicated by the wide range of chemical functionalities and modes of operation exhibited by the antibiotic materials of physiological significance in use today. As demonstrated, chromatographic methods provide many of the advantages necessary for screening applications. Judicious choice of sample preparation method, separation mode and detection strategy can provide significant immunity from problems associated with the food matrix. Gas chromatography can provide extremely high separation efficiencies, however, only a limited number of antibiotic compounds are inherently volatile enough for direct analysis by gas chromatography. Derivatization to enhance the volatility of the antibiotic is one approach to overcome this limitation. Among the methods available, reversed-phase high-performance liquid chromatography is used extensively for the analysis of many antibiotic systems as it does not require derivatization and it combines relatively high separation efficiencies with low detection limits. The diverse group of properties exhibited by the antibiotic materials in use today suggests that the choice of detection strategy is a key component in the successful development of an analysis technique. Derivatization of the antibiotic material is frequently used to add either a fluorogenic of chromogenic moiety to the antibiotic compound to enhance detection. Derivatization procedures suffer from several limitations which are problematic when making measurements in complicated food matrices. Among the different detection modes utilized for antibiotic analysis, polarimetric detection has the potential to provide extremely selective detection of most antibiotic materials, and this selective response can minimize many of the constraints placed upon the separation system by the sample matrix. Although many of the separation modes used for antibiotic analysis are well developed, separations based on capillary electrophoretic methods have much potential in the field of antibiotic analysis. Future investigations are needed to extend the generality of these techniques and expand their use into the field of food analysis. PMID- 1494004 TI - Chromatographic methods of analysis for penicillins in food-animal tissues and their significance in regulatory programs for residue reduction and avoidance. AB - Chromatographic methods for penicillin analysis in animal tissues play a significant role in the regulation of the use of these drugs in livestock production. Regulatory agencies rely on data generated from these methods to establish withdrawal times and to determine whether presumptive positive tissue samples from slaughtered animals intended for human consumption contain violative levels of penicillins to necessitate regulatory action. The need to develop sensitive, accurate, and reliable methods to support regulatory programs is examined together with emerging techniques that could be taken advantage of to improve the sensitivity and usefulness of current chromatographic methods for tomorrow's regulatory agency. PMID- 1494005 TI - Chromatographic methods for tetracycline analysis in foods. AB - The tetracyclines have served for decades as an important class of antibiotics in food animal health and production. As such, they have also been a source of concern for residue monitoring authorities around the world. In response to this concern a number of microbial inhibition, immunoassay and bacterial receptor methods have evolved for the detection of this class of compounds in various foods of animal origin. However, these methods often lack specificity and are subject to false positive and false negative results. For these reasons a number of chromatographic methods for the separation and determination of the tetracyclines isolated from foods have been developed that are capable of identifying and quantifying individual tetracycline drugs. We present here an overview of tetracycline analytical methods, including microbial inhibition, immunoassay and receptor technologies for detection, techniques for isolation from food matrices, and thin-layer chromatographic, high-performance liquid chromatographic, gas chromatographic and mass spectrometric procedures for determination of this class of compounds. A discussion of the variables involved in such methodology and a review of method criteria are offered. PMID- 1494006 TI - Thin-layer chromatography-flame ionization detection Iatroscan system. AB - The thin-layer chromatography-flame ionization detection (TLC-FID) Iatroscan system is a technique which is still being evolved. Quantification with the TLC FID system relies heavily on the accurate setting up and calibration of the instrument. An appreciation of the factors that influence the analysis can eliminate significant errors. At least a few of the numerous operating variables need to be fixed to obtain coherent results from different laboratories. Hydrogenation of the sample is recommended in order to improve quantification with the Iatroscan system. The improved reproducibility obtained with automatic sample spotters compared with manual spotting indicates that autosampling is highly advisable. PMID- 1494007 TI - Chromatographic analysis of cis/trans carotenoid isomers. AB - Cis/trans configurations of carotenoids are known to effect the biochemistry of carotenoids in certain situations. Methodology for separating carotenoid cis/trans isomers is of importance to nutritionists and food scientists because cis isomers of provitamin A carotenoids have lower provitamin A activities than the all-trans form. Traditional food processing and preservation methods, especially thermal treatments, induce the formation of cis isomeric forms. However, many challenges, are apparent for identifying and analyzing cis/trans isomers present in foods and other biological tissues. The development of current chromatographic methods for the separation of carotenoid cis/trans isomers is reviewed. For the separation of beta-carotene isomers, most procedures employ either Ca(OH)2 or Vydac C18 columns. In general, polymeric C18 columns allow for the detection of cis carotenes, while monomeric C18 columns provide for some separation of certain xanthophylls. The main cis isomers detected in foods are the 13-cis and 9-cis forms, although other forms have also been found (mainly 15 cis and various di-cis isomers). More studies involving the metabolism and physiological consequences of cis/trans isomers in the diet are needed. However, due to limitations in current techniques, further method development in the area of separation, detection and quantitation of cis/trans carotenoid isomers will be required. PMID- 1494008 TI - Chromatographic methods for the analysis of heterocyclic amine food mutagens/carcinogens. AB - A series of potent heterocyclic amines that are mutagenic and carcinogenic have been discovered that are formed in some heated foods, most notably, meats derived from muscle. Determining the heterocyclic amine content in foods and food products is required for toxicological research, industry quality control, and possibly in the future, regulatory control. The contents of food needs to be determined using reliable analytical techniques. Since heterocyclic amines are present in foods at ng/g levels, a variety of liquid-liquid or solid-phase purification techniques are required, followed by gas or high-performance liquid chromatography. Peak detection has been successful using UV, fluorescence, and mass spectrometric detection, and biological activity using the Ames/Salmonella test. The low levels present require that chromatographic efficiency, and both detector sensitivity and selectivity be optimized. The cartridge solid-phase extraction and high-performance liquid chromatography method have been used to measure the known food-derived heterocyclic amines for several types of food, and to the authors knowledge, this is the only method undergoing intralaboratory comparison and validation. Our analysis of the literature shows that chromatographic analysis of the heterocyclic amines by high-performance liquid chromatography or gas chromatography (with derivatization) is satisfactory for heterocyclic amine analysis in foods although the methods are just now being optimized for routine use. The biggest improvements in speed and accuracy will probably come from improved extraction methods as analysis of complex food samples for heterocyclic amines will always be a challenge. PMID- 1494009 TI - Chromatography of tea constituents. AB - Modern chromatographic techniques such as high-performance liquid chromatography are currently the most helpful approach to the routine analysis of and research of non-volatile tea constituents. Using these techniques some errors in the more classical analytical techniques could be detected. Unfortunately, some of these methods of analysis are still in widespread use, even as official methods. However, knowledge of especially the polyphenols in tea is still lacking, and for many of the minor polyphenols no chromatographic methods for the determination exist. PMID- 1494010 TI - Sample preparation for chromatographic analysis of food. AB - Sampling, homogenisation and sample preparation prior to chromatographic injection of food analytes are designed to enhance accuracy and precision. The reduction of inherent errors introduced by these steps requires the analyst's attention as a matter of course. Methods and examples of minimising errors in each step are reviewed. PMID- 1494011 TI - Analysis of organic micropollutants in the lipid fraction of foodstuffs. AB - An overview is given of current techniques for the analysis of organic micropollutants that accumulate in the fatty fraction of foodstuffs, such as pesticides, polychlorinated biphenyls, polycyclic aromatic hydrocarbons, polychlorinated dibenzodioxins and polychlorinated dibenzofurans. Isolation and clean-up are considered to be of great importance in the field of residue analysis. In general, problems are related to the low levels of the individual compounds at which they usually occur and the complexity of extraction and clean up procedures for isolating and separating analytes from matrix components and other contaminants. Therefore, special attention is focused on sample pretreatment and on coupled chromatographic techniques, showing developments towards multi-residue methods, miniaturization and automation of analytical procedures. Coupling of chromatographic techniques with spectroscopic techniques is also considered as an important tool for identification and confirmation purposes. PMID- 1494012 TI - Determination of aflatoxins in food products by chromatography. AB - Several chromatographic methods for the determination of aflatoxins in agricultural and food products are reviewed. During the past two decades, identification and determination of aflatoxins were done by thin-layer chromatography (TLC) because it was easy, fast and inexpensive. However, high performance liquid chromatography (HPLC) using fluorescence detection is now the method of choice for determining aflatoxins and is also growing in popularity for their identification. The reasons for selecting HPLC over TLC can be summarized as the ability to analyze for a wide variety of compounds, including compounds that are easily degraded by heat, light or air, the ease of adaptation to confirmatory procedures, the potential for automation and the dramatic improvement in instrumentation, including the development of increasingly sensitive fluorescence and electrochemical detectors and short, high-resolution, reversed-phase columns. PMID- 1494013 TI - Chromatographic methods for the determination of pesticides in foods. AB - Chromatography is the most important technique available to the analyst dealing with the determination of pesticide residues in food, feed and environmental samples. Numerous methods for pesticide residues in foods have been developed in the past few years, and this paper reviews some of the most important procedures. A great variety of chromatographic methods, such as solid-phase extractions, column chromatographic clean-up methods, thin-layer, gas, high-performance liquid and supercritical fluid chromatography, and their coupling with sensitive and selective detection methods are surveyed. PMID- 1494014 TI - Chromatographic separation of cholesterol in foods. AB - Based on the current literature and on experience gained in the laboratory, a simplified procedure using direct saponification (0.4 M potassium hydroxide in ethanol and heating at 60 degrees C for 1 h) is the most appropriate method for the determination of total cholesterol in foods. Extraction of the unsaponifiable matter with hexane is efficient and no extra clean-up is required before quantification. An internal standard, 5 alpha-cholestane or epicoprostanol, should be added to the sample prior to saponification and, together with reference standards, carried through the entire procedure to ensure accurate results. A significant improvement in cholesterol methodology has been achieved by decreasing the sample size and performing all the sample preparation steps in a single tube. The method has the advantages of elimination of an initial solvent extraction for total lipids and errors resulting from multiple extractions, transfers, filtration and wash steps after saponification. The resulting hexane extract, which contains a variety of sterols and fat soluble vitamins, requires an efficient capillary column for complete resolution of cholesterol from the other compounds present. The development of fused-silica capillary columns using cross-linked and bonded liquid phases has provided high thermal stability, inertness and separation efficiency and, together with automated cold on-column gas chromatographic injection systems, has resulted in reproducible cholesterol determinations in either underivatized or derivatized form. If free cholesterol and its esters need to be determined separately, they are initially extracted with other lipids with chloroform-methanol followed by their separation by column or thin-layer chromatography and subsequently analysed by gas or liquid chromatography. Although capillary gas chromatography offers superior efficiency in separation, the inherent benefits of liquid chromatography makes it a potential alternative. Isotope dilution mass spectrometry has been widely accepted as a reliable analytical method for highly accurate determination of cholesterol in serum and several definitive methods have been reported. The combination of capillary gas chromatography with mass spectrometry has become an excellent approach for the determination of cholesterol in complex mixtures of sterols and tocopherols, providing high resolution with positive identification. When used to determine cholesterol in multi-component foods, spectrophotometric methods have been documented to overestimate significantly the amount of cholesterol owing to the presence of other interfering substances. A re evaluation of food products should be undertaken using the more specific chromatographic methods to accumulate data that will more accurately reflect the true cholesterol content. PMID- 1494015 TI - Gas chromatography of fatty acids. AB - Lipids in foods contain a wide variety of fatty acids differing in chain length, degree of unsaturation, position and configuration of double bonds and the presence of special functional groups. Modern capillary gas chromatography offers excellent separation of fatty acids. Fused-silica capillary columns with stationary phases of medium polarity and non-polar methylsilicone stationary phases successfully separate most of the natural fatty acids. Special applications, such as the separation of complex cis-trans fatty acid mixtures and cyclic fatty acids, required particular chromatographic conditions, including the use of very long capillary columns or more polar stationary phases. The derivatization methods for the preparation of fatty acid esters also need to be optimized to obtain accurate quantitative results. This paper reviews the derivatization techniques, capillary columns and stationary phases commonly used in the gas chromatography of fatty acids in food. PMID- 1494016 TI - Drug residue analysis using immunoaffinity chromatography. AB - The background and applicability of immunoaffinity chromatographic separations and clean-up to drug residue analysis of agricultural commodities is discussed. The uses of antibody specificity for separation and concentration of drug residues are presented. Examples of immunoaffinity chromatography for the determination of residues of (1) nortestosterone and methyl testosterone in swine muscle, urine and bile; (2) chloramphenicol in swine tissue, eggs and milk; (3) clenbuterol in calf urine; (4) zeranol and beta-zearalanolin in calf urine: (5) diethylstilbestrol, dienestrol and hexestrol in calf urine are presented. Further, examples of the successful coupling of immunoaffinity separations with other chromatographic techniques such as gas chromatography and high-performance liquid chromatography are presented. PMID- 1494017 TI - High-performance liquid chromatographic methods for the determination of sulfonamides in tissue, milk and eggs. AB - In the last decade, significant research has been done to improve the existing high-performance liquid chromatographic (HPLC) methods and also towards developing simple, reliable and sensitive HPLC methods for sulfonamides in meat, milk and eggs. The replacement of solvent extraction with solid-phase extraction or matrix solid-phase dispersion techniques is a step forward. Significant improvements in sensitivity have been achieved. This review concentrates on HPLC methods for the determination of sulfonamides in foods of animal origin published after 1980. The existing methods are critically evaluated and suggestions for future research are made. PMID- 1494018 TI - Methods for the determination of sulphonamides in meat. AB - Sulphonamides, due to their important antibacterial effects, are widely used in veterinary practice and animal husbandry. Residues arising from administration without observing withdrawal time sufficiently are normally the parent compounds and the N4-acetyl derivatives, the latter being hydrolyzed to the parent compounds only during extraction under acidic conditions. It is therefore quite conceivable that many authors concentrate on determining these metabolites. In the past decade, we have witnessed a considerable increase in new analytical techniques dealing with the determination of sulphonamides. Among these procedures, especially the so-called multimethods using high-performance liquid chromatography--though sometimes including toilsome clean-up steps--can be mentioned. However, current approaches also utilize gas chromatography, gas chromatography-mass spectrometry, liquid chromatography-mass spectrometry, supercritical fluid chromatography-mass spectrometry, thin-layer chromatography and immunological methods. For most of these techniques, a strong trend towards lowering the level of detectability (down to the sub-ppb range) and improving accuracy and reproducibility can be established. PMID- 1494019 TI - Phycotoxins in seafood--toxicological and chromatographic aspects. AB - Two typical clinical types of algae-related seafood poisoning have attracted medical and scientific attention: paralytic shellfish poisoning (PSP) and diarrhetic shellfish poisoning (DSP). Therefore, it became necessary to establish methods for the evaluation of possible hazards caused by contamination of seafood with these phycotoxins. Bioassays with mice or rats are the common methods for the determination of the toxin content of seafood. However, biological tests are not completely satisfactory because of a lack of sensitivity and pronounced variations. Additionally, there is growing opposition against animal testing. Therefore, many efforts have been undertaken to determine phycotoxins by chromatographic methods. PSP determination is mainly based on high-performance liquid chromatographic (HPLC) separation by ion-pair chromatography followed by postcolumn oxidation of the underivatized toxins in alkaline solution and fluorescence detection. HPLC methods for the determination of the DSP toxins okadaic acid (OA) and dinophysistoxin-1 (DTX-1) are characterized by precolumn derivatization with 9-anthryldiazomethane (ADAM) and/or 4-bromomethyl-7 methoxycoumarin (Br-Mmc), followed by chromatographic separation of the DSP esters formed and fluorescence detection. The chromatographic methods discussed in this review allow the rapid, sensitive and non-ambiguous determination of individual species of the two most important phycotoxins in seafood, PSP and DSP. PMID- 1494020 TI - Application of ion chromatography to the determination of inorganic anions in foodstuffs. AB - A review on the applications of ion chromatography (IC) to the determination of inorganic anions in foodstuffs is presented. The anions were commonly determined in food, i.e., SO3(2-), NO3- and NO2-, and to a lesser extent Cl-, Br-, I-, SO4(2 ), IO3-, BrO3- and phosphate, are considered. In comparison with standard methods for the determination of anions in food products, chromatographic methods are rapid, sensitive and precise. They also have the advantage of determining several ions simultaneously. The separation may be achieved by conventional IC, by ion interaction chromatography or by ion exclusion chromatography. IC has also been applied to the determination of Br, I, N and S in foods after oxidation or combustion of samples and conversion into anionic forms. PMID- 1494021 TI - Electrophoresis and chromatography of wheat proteins: available methods, and procedures for statistical evaluation of the data. AB - Analysis of gluten proteins from the wheat grain endosperm has long challenged the analytical chemist. Several hundred unique polypeptides are present, many in large polymers. This complexity, plus useful relationships of composition to genotype and quality, encouraged development and application of electrophoresis and chromatography for gluten analysis. We review the methods of polyacrylamide gel electrophoresis, sodium dodecyl sulfate-polyacrylamide gel electrophoresis, isoelectric focusing and high-performance liquid chromatography available for study of wheat proteins. Singly and in combination, they provide rapid, reproducible, high-resolution separations based on size, charge, or surface hydrophobicity. As challenging and important as the analyses themselves, however, is interpretation of data. Subjective evaluation is sometimes possible, but statistical methods such as similarity scores, clustering, principal components, multiple linear regression, and partial least squares now are increasingly used for data analysis. We review the use of these procedures, and precautions necessary to avoid misinterpretation of data. Optimal evaluation of protein analytical data will enhance the value of such analyses in wheat breeding, marketing, and processing. PMID- 1494022 TI - Chromatographic and electrophoretic methods used for analysis of milk proteins. AB - Current knowledge of milk proteins and their behavior in dairy foods is based on early applications of chromatography and electrophoresis. Electrophoretic identification of the number and genetic variety of milk proteins inaugurated a research effort in which chromatographic techniques were successfully applied to the isolation of each milk protein, thus facilitating the characterization and further study of milk and dairy products. This review focuses on recent applications of chromatography for separations and analysis and on analytical applications of electrophoresis. PMID- 1494023 TI - The effect of teratogens on maternal corticosterone levels and cleft incidence in A/J mice. AB - It is unknown whether orofacial clefting, one consequence of teratogenic exposure, results from a direct interaction between the teratogen and the embryonic palate, or indirectly from maternal alterations caused by the teratogen. In the current study pregnant A/J mice were exposed to one of three cleft-inducing agents in order to examine the relationship between drug-induced clefting and the response of maternal plasma corticosterone to drug administration. The agents used, haloperidol (HAL), 2,4,5-trichlorophenoxyacetic acid (2,4,5-T), or phenytoin (PHT), were administered in teratogenic doses between 0800 and 0930 on gestational day 10 (GD 10). For corticosterone determinations, mice were dosed on GD 10, and blood was collected at 1, 4, 24, or 48 hr after dosing. For fetal evaluation of cleft lip and/or cleft palate, mice were dosed on GD 10 and killed on GD 18. Phenytoin was the most potent inducer of cleft lip and palate and induced a sustained elevation of plasma corticosterone in maternal animals. The other treatments, in order of decreasing potency to induce clefting and/or cause an elevation of corticosterone in plasma were 2,4,5 T > HAL > controls. Correlations between maternal corticosterone levels and clefting incidence were very high at all time points examined; total exposure (area under the curve) was also highly correlated. A linear relationship between drug-induced increases in maternal corticosterone levels and the incidence of clefting in A/J mice was evident. Based on these findings, we believe that increased maternal corticosterone levels may play a role in orofacial clefting in A/J mice. PMID- 1494024 TI - H-2 haplotype and heterochronic orofacial morphogenesis in congenic mice: consideration as a possible explanation for differential susceptibility to teratogenesis. AB - For over 40 years it has been known that genetically different inbred strains of mice have different degrees of susceptibility to corticosteroid-induced cleft palate. Gene(s) at or near the H-2 region on chromosome 17 have been implicated. One postulated explanation is that the strain difference in susceptibility is not related to differential corticosteroid action, but to differences in normal developmental pattern. Studies have demonstrated significant quantitative differences between inbred strains for a number of growth variables relative to palatal development. It is also known that there are genes at or near the H-2 complex that influence pre- and post-implantation development. Thus, we sought to determine the relationship in H-2 congenic mice between haplotype differences and variation in normal orofacial development. Morphometric analyses of the palatal region in serially sectioned E13 and E17 B10 and B10.A mice were completed. We were able to find some evidence for H-2 haplotype related phenotypic differences, but these differences are less than compelling as an explanation for haplotype dependent susceptibility differences. A more likely explanation is GR-mediated differential corticosteroid responsiveness and its consequent effects on palatal shelf growth. PMID- 1494025 TI - Perspectives on holoprosencephaly: Part II. Central nervous system, craniofacial anatomy, syndrome commentary, diagnostic approach, and experimental studies. AB - This paper presents an updated analytic review of the holoprosencephalic disorders. Central nervous system findings and craniofacial anatomy are discussed in depth. Associated anomalies and syndromes are updated with a syndrome commentary that attempts to separate durable syndromes from associated anomalies and spurious entities. The differential diagnosis of various conditions that may simulate the holoprosencephalic disorders is also discussed. Various experimental approaches to holoprosencephaly are reviewed, indicating that holoprosencephaly appears to be both etiologically and pathogenetically heterogeneous. PMID- 1494026 TI - Quaternary and subunit structure of Calliphora arylphorin as deduced from electron microscopy, electrophoresis, and sequence similarities with arthropod hemocyanin. AB - Arylphorin was purified from larvae of the blowfly Calliphora vicina and studied in its oligomeric form and after dissociation at pH 9.6 into native subunits. In accordance with earlier literature, it was electrophoretically shown to be a 500 kDa hexamer (1 x 6) consisting of 78 kDa polypeptides (= subunits). Electron micrographs of negatively stained hexamers show a characteristic curvilinear, equilateral triangle of 12 nm in diameter (top view) and a rectangle measuring 10 x 12 nm (side view). Alternatively, particles in the top view orientation exhibit a roughly circular shape 12 nm in diameter. Crossed immunoelectrophoresis revealed the presence of a major subunit type; the nature of a very minor and a third immunologically separated component remains unclear. A novel 2 x 6 arylphorin particle was detected and isolated. It comprises less than 10% of the total arylphorin material and shows a long, narrow interhexamer bridge in the electron microscope. An arylphorin dissociation intermediate identified as a trimer (1/2 x 6) was isolated; its possible quaternary structure is discussed on the basis of electron micrographs. The epitope of monoclonal antibody Ec-7 directed against tarantula (Eurypelma californicum) hemocyanin subunit d and also reactive to Calliphora arylphorin was traced to a highly conserved peptide of 27 amino acids localized in the center of the protein. The primary structure of Calliphora arylphorin as published in our preceding paper (Naumann and Scheller 1991) is compared in detail to the sequences of spider and spiny lobster hemocyanin. This revealed a basic framework of 103 strictly conserved amino acids. Isofunctional exchanges are proposed for another 76 positions. On the basis of these similarities, and the published three-dimensional model of spiny lobster hemocyanin, a detailed model of the quaternary structure of Calliphora arylphorin is presented. A second larval storage protein previously termed protein II was purified from Calliphora hemolymph. It was demonstrated to be a 500 kDa hexamer of 83 kDa subunits. In the electron microscope it shows a cubic view 9 nm in length with a large central hole and a rectangular view (9 x 10 nm) with a large central cavity. A morphologically very similar hemolymph protein was detected in Drosophila melanogaster larvae. From its structural appearance it is uncertain whether protein II belongs to the hemocyanin superfamily or not. PMID- 1494027 TI - Effects of corticosteroids on short-circuit current across the cecum of the domestic fowl, Gallus domesticus. AB - Both avian corticosteroid hormones, aldosterone and corticosterone, increased short-circuit current across the wall of the ceca of the domestic fowl (Gallus domesticus) in vitro. About 80% of this short-circuit current was inhibited by the Na-channel blocking drug amiloride. Corticosterone was about ten times less potent than aldosterone in increasing short-circuit current and it exerted a similar maximal effect. Cortisol (an endogenous corticosteroid hormone in mammals but not birds) was about ten times less potent than corticosterone and this difference appeared to reflect the presence of the 17 alpha-OH group in cortisol. Carbenoxolene, which inhibits 11 beta-hydroxysteroid dehydrogenase, increased the effect of corticosterone. This effect is consistent with inhibition of the metabolism of corticosterone to 11-dehydrocorticosterone. The latter was found to be about 100 times less potent than corticosterone. The effects of both aldosterone and corticosterone (also dexamethasone) were abolished by the mineralocorticoid receptor antagonist spironolactone. The results suggest that corticosterone has an effect similar to aldosterone but in vivo its action may be depressed by the activity of 11 beta-hydroxysteroid dehydrogenase. The sensitivity of the cecal preparations to corticosterone indicates that this hormone could contribute to the regulation of transcecal Na transport (absorption) in vivo. PMID- 1494028 TI - Body temperature and metabolic rate during natural hypothermia in endotherms. AB - During daily torpor and hibernation metabolic rate is reduced to a fraction of the euthermic metabolic rate. This reduction is commonly explained by temperature effects on biochemical reactions, as described by Q10 effects or Arrhenius plots. This study shows that the degree of metabolic suppression during hypothermia can alternatively be explained by active downregulation of metabolic rate and thermoregulatory control of heat production. Heat regulation is fully adequate to predict changes in metabolic rate, and Q10 effects are not required to explain the reduction of energy requirements during hibernation and torpor. PMID- 1494029 TI - Capacitance, short-circuit current and osmotic water flow across different regions of the isolated toad skin. AB - The amphibian antidiuretic hormone, arginine vasotocin, stimulated osmotic water flow across isolated skin from the pelvic but not the pectoral skin of the toad, Bufo woodhouseii. Changes in the apical membrane capacitance were not observed for either region of the skin following treatment with arginine vasotocin when there was an osmotic gradient across the tissue. In the absence of an osmotic pressure gradient, the apical membrane capacitance of the pelvic skin increased from 2.8 +/- 0.5 to 3.3 +/- 0.6 microF.cm-2 after treatment with 5 x 10(-8) M arginine vasotocin. Under these conditions, apical membrane capacitance of the pectoral skin was 1.8 +/- 0.1 microF.cm-2 and did not change significantly after arginine vasotocin treatment. The amiloride-sensitive short-circuit current across the pelvic skin was stimulated by arginine vasotocin as was the density of channels in the apical membrane as determined by fluctuation analysis. Values for channel density in the pelvic skin also correlated with apical membrane capacitance and increased from 90 to 273 channels per micron2 of estimated membrane area following arginine vasotocin treatment. In the pectoral skin the stimulation of short-circuit current following arginine vasotocin treatment was small and an increase in channel density could not be demonstrated. The current through single Na+ channels in both regions of the skin did not different either before or after arginine vasotocin treatment. PMID- 1494031 TI - The relative importance of photoperiod and temperature as cues for seasonal acclimation of thermoregulation in pouched mice (Saccostomus campestris: Cricetidae) from southern Africa. AB - The effect of short photoperiod and cold on metabolism and thermoregulation was investigated in pouched mice (Saccostomus campestris: Cricetidae) from three localities in southern Africa which experience contrasting climatic conditions. Mice were initially acclimated to long photoperiod (14L: 10D) at 25 degrees C, followed first by a decline in photoperiod (to 10L: 14D) and then by a fall in temperature (to 10 degrees C). Minimum observed metabolic rate (identical to basal metabolic rate) was unaffected by the decline in photoperiod but increased significantly following cold acclimation. Because minimal thermal conductance remained constant throughout the study the increase in minimum observed metabolic rate caused a decline in lower critical temperature to around 26 degrees C. In contrast to minimum observed metabolic rate, regulatory non-shivering thermogenesis improved significantly following the decline in both photoperiod and temperature. However, pouched mice from the warmest locality were significantly less responsive to photoperiod than those from the other two localities whose survival might depend upon their ability to accurately predict seasonal changes in temperature. Neither photoperiod nor temperature had any effect on body mass, yet pouched mice from the most arid locality, where food supply might be unpredictable, were significantly smaller and had lower total energy requirements than those from areas experiencing higher annual rainfall. These results indicate that S. campestris displays considerable geographical variation in energy requirements together with differences in the use of photoperiod as an anticipatory cue for predicting the onset of winter. These differences appear to be related to the availability of energy and the relative severity of climatic conditions in each locality. PMID- 1494030 TI - Ventilatory accommodation of changing oxygen demand in sciurid rodents. AB - Ventilation was measured across a range of O2 consumption rates in four sciurid rodents: Tamias minimus (47 g), Spermophilus lateralis (189 g), S. beecheyi (531 g), and Marmota flaviventris juveniles (1054 g) and adults (2989 g). Maximum thermogenic oxygen consumption was measured for all but adult M. flaviventris. Aerobic scopes (maximum/minimum O2 consumption rates) were 4.6, 3.8, 5.4, and 4.8 in T. minimus, S. lateralis, S. beecheyi, and juvenile M. flaviventris, respectively. Aerobic scope was at least 4.1 in adult M. flaviventris. Ventilatory accommodation of changing O2 consumption rate was qualitatively similar in the four species, with the bulk of accommodation resulting from changes in minute volume. Nevertheless, there were significant differences in the relative importance of frequency, tidal volume, and O2 extraction in accommodation. In all species, frequency and minute volume were strongly correlated to O2 consumption rate. Tidal volume was significantly correlated to O2 consumption rate in T. minimus and S. beecheyi, but not in the other species. Oxygen extraction was not significantly correlated to O2 consumption rate in any species. Analysis of factorial ventilation changes across a standardized 3.8-fold change in O2 consumption rate revealed significant differences among species in frequency and O2 extraction, but not in tidal or minute volume. When compared to a generalized allometry for mammalian resting ventilation, the four sciurid species had consistently lower respiration frequency and higher O2 extraction than predicted, perhaps because the sciurid measurements were made on unrestrained animals. There was no indication that ventilation constrained maximum O2 consumption rate. PMID- 1494032 TI - A non-organic and non-enzymatic extraction method gives higher yields of genomic DNA from whole-blood samples than do nine other methods tested. AB - We compared ten methods for extraction of DNA from whole blood. Nine methods require incubation with either enzymes or treatment of organic solvents or both. The 'Rapid Method' (RM) (Method 10) avoids the use of organic solvents (phenol/chloroform) and eliminates completely the use of proteinase K. Thus, the time and cost of DNA extraction are reduced significantly. This is accomplished by salting out and precipitation of the cellular proteins in saturated sodium chloride. This method takes less than an hour to completion, without compromising the yield or the quality of DNA. Using RM, we can make DNA from 0.1 ml of whole blood and as little as 0.5 ml of blood yields DNA sufficient to run a few Southern blots. The RM can also be applied to packed cells. The DNA is free of RNA, protein and degrading enzymes. The uncut DNA runs as a typical slow migrating, high-molecular-weight and undegraded species in an agarose gel. The DNA is suitable for digestion by various restriction endonucleases. This procedure works equally well with fresh blood samples and with those that are stored at 4 degrees C and -70 degrees C. To our knowledge the RM reported here is the safest, fastest and most quantitative and economical method for preparation of DNA from whole blood and cells. PMID- 1494033 TI - Measurement of pH to quantify urease activity. AB - The rate of change of pH caused by the hydrolysis of urea was measured for urease solutions of 18 different concentrations. Concentrations were converted into an activity, A (measured in IU/cm3), by using a titrimetric method to assay the urease sample. For activities in the range 0.6-38 IU/cm3, A was related to the initial rate of change of pH, (dpH/dt)0, (measured in s-1) by the empirical relationship: A = 549(dpH/dt)0-1423(dpH/dt)2(0). Values of (dpH/dt)0 were sensitive to changes in the urease activity of about 0.6 IU/cm3. PMID- 1494034 TI - HPLC analysis of hexosamine phosphates in biological samples. AB - Galactosamine is quickly metabolized to galactosamine 1-phosphate in rats treated with this compound. An HPLC method to quantify hexosamine phosphates in biological samples is described, modified from the o-phthaldialdehyde amino acid analysis procedure. o-Phthaldialdehyde derivatives of hexosamines and hexosamine phosphates can be eluted from a reverse-phase column at different retention times, with a total analysis time of 30 min and without overlapping with free amino acids at physiological concentrations. The standard curves are linear between 1 and 40 nmol. This simple method is more selective and sensitive than previous enzymatic analyses of hexosamine phosphorylation. PMID- 1494035 TI - Microdetermination of G6PD isoenzyme activity in human erythrocytes by thin-layer PAG-IEF. AB - An improved method of microdetermination of G6PD isoenzyme activity in human erythrocytes was developed by modification of previously reported procedures. The volume of blood samples was reduced from 2 ml to 20 microliters. After hemolysis in 2% Triton X-100 and 0.1% beta-mercaptoethanol, the samples were subjected to centrifugation and thin-layer isoelectric focusing in polyacrylamide gel (PAG IEF). By comparison with the original method, excellent resolution was obtained by this more rapid and simple procedure. PMID- 1494036 TI - Separation of (R)- and (S)-naproxen using micellar chromatography and an alpha 1 acid-glycoprotein column: application for chiral monitoring in human liver microsomes by coupled-column chromatography. AB - A column-switching system for fast determination of (R)- and (S)-naproxen in liver microsomes has been developed. The centrifuged sample was injected directly onto a pre-column with octadecylcoated silica. The retained analytes were then directed to an alpha 1-AGP column using a mobile phase composed of phosphate buffer (pH 6.5), dimethylocytylamine (30 mM) and the nonionic surfactant, Tween 20 (40 g/l). The method gave high absolute recoveries and good repeatabilities: 99.6% (1.7% relative standard deviation) and 94.9% (2.4% R.S.D.) for the (R)- and (S)-naproxen, respectively. The use of a surfactant in combination with an aliphatic amine in the mobile phase involves reduced retention times with retained enantioselectivity. Furthermore, the presence of the surfactant makes it possible to inject biological samples directly into the chromatographic system. PMID- 1494038 TI - [The ultrastructure of accumulated mitochondria in injuries of demyelinated axons]. AB - The authors ligated the nervus lienalis of the cat, and observed the subsequent accumulation of mitochondria in nonmyelinated axons in close vicinity proximal and distal to the ligature. In enlarged axons they found groups of mostly homogen population of mitochondria with specific morphologic signs. Concerning the mitochondrial ultrastructure authors arranged the mitochondria to three classes and five subclasses. The authors discuss the aim and function of mitochondrial accumulation in the injured nonmyelinated axon. Different directions of mitochondrial group's motion in axons was hypothetically assumed. PMID- 1494037 TI - Coupling of antibody-binding fragments to solid-phase supports: site-directed binding of F(ab')2 fragments. AB - A method to covalently bind antibody fragments, via their carboxyl termini to solid supports, is presented. The strategy involves: (1) reversibly blocking all the accessible carboxyl groups on the antibody molecule with phenylhydrazine, (2) exposing the carboxyl termini of the fragment by enzymatic digestion with pepsin and (3) subsequently coupling the fragment to an appropriate support. Experiments with an anti-bovine serum albumin monoclonal antibody and C-14 phenylhydrazine revealed that the blocking step was nearly completely reversible with a dilute solution of FeCl3. Radioiodinated blocked F(ab')2 fragments were then coupled to an amino-functionalized Sepharose 4B column, and characterized as to their coupling capacity (mass of protein coupled/ml of bead), and antigen-binding activity. The coupling capacity of the blocked fragments was found to be 12%, half the coupling efficiency of unmodified radioiodinated F(ab')2. The antigen binding capacity (mol antigen bound per mol antibody coupled) for the blocked F(ab')2, on the other hand, was found to be 1.9, which was approx. 3.5-times greater than for the unmodified F(ab')2. Comparisons with other conventional coupling techniques were also made. These preliminary studies suggest that this technique can provide one with the means to obtain more uniform and active populations of immobilized antibody fragments. PMID- 1494039 TI - Insulin-like immunoreactivity persists in the spinal cord of streptozotocin induced diabetic rats. AB - In both saline-injected control and streptozotocin-induced diabetic rats, insulin like immunoreactivity was localized in the cervical, thoracic, lumbar and sacral segments of the spinal cord. This insulin-like immunoreactivity was consistently localized in the neurons and dendrites from control rats as well as from diabetic rats ranging from 1 month to 12 months after diabetes induction. In the neuronal cell bodies, the reaction product was predominantly localized in the cell nucleus and the proximal and distal dendrites. In the labelled cell nucleus, the reaction product was scattered throughout the cell cytoplasm and nucleoplasm, but not within the nucleolus. The inner and outer nuclear membranes were also labelled. In labelled dendrites, the reaction product was closely associated with the parallel arrays of neurotubules, plasma membranes and synaptic densities. Most of the labelled distal dendrites were postsynaptic to unlabelled axon terminals. A labelled dendrite often formed the central element of a synaptic glomerulus with several unlabelled axon terminals. It is hereby hypothesized that some of the neurons in the spinal cord of the diabetic rat are capable of synthesizing insulin-like substance(s), which appears to be involved in neurotransmission and neuromodulation. PMID- 1494040 TI - Primary olfactory terminations in the forebrain of amphibia: a comparative study with soybean agglutinin. AB - Ambystoma and Xenopus were used to investigate olfactory terminations in the forebrain by exploiting the selective binding of soybean agglutinin to primary olfactory projections. Lectin binding and tridimensional reconstruction provided new information on the distribution of olfactory glomeruli and on regional and interspecific differences. Ambystoma showed an uniform labelling of all olfactory terminations, which were localized in the rostro-lateral forebrain without obvious segregation of different terminal fields, except at dorsal levels. On the contrary, the binding pattern of Xenopus confirmed the existence of three sets of primary olfactory neurons characterized by clear differences in lectin binding. Selective soybean agglutinin binding and a detailed tridimensional reconstruction provided evidence for the existence of a set of neuronal projections, described for the first time, which terminate in a discrete bilateral region of the forebrain localized below the main olfactory bulb. The presence of three different sets of primary olfactory neurons, the experimental potentials and the possible functional significance of SBA binding sites are discussed. PMID- 1494041 TI - Axonal and non-axonal immunolocalization of cytosolic aspartate aminotransferase (cAATase), GABA and glutamic acid decarboxylase (GAD) in the rat cochlear nucleus. AB - The localization of both cAATase activity, by histoenzymological method, and the immunoreactivity against cAATase, were investigated in the cochlear nucleus of rats. The immunohistochemical determination of cAATase was carried out using the PAP method, with an antiserum obtained from rabbits immunized with porcine cAATase. It was also studied both the immunolocalization of GABA-like and GAD like substances. Our observations, with light microscope, revealed weak cAATase activity in the small neurons, and a more intense one in the fibers surrounding neuronal bodies. The large neurons presented a very weakly activity within their neuronal bodies and dendrites, but it was strongly found in granulations that surround the perikaryon and dendrites. cAATase immunoreactivity presents the same distribution as the enzymological activity. In the same way, we have investigated the pattern of distribution of both GABA- and GAD-like substances. Immunolocalization of these substances was similar to that found for cAATase. In the control sections incubated with Gostatin (0.05 mM), cAATase activity was absent. The immunoreactivity was also negative in every immunohistochemical control sections. These facts suggest that aspartate could intervene as a co neurotransmitter or neuromodulator in the rat cochlear nucleus, and that axonic endings could contain cAATase, GABA and GAD. It was also found immunoreactivity against cAATase, GABA and GAD, in neuronal bodies, dendrites and glial processes, in close association with capillary wall. These observations have led us to suggest the possible co-localization and co-release of both GABA and aspartate from synaptic and non-synaptic sites in the cochlear nucleus. PMID- 1494042 TI - Ultrastructural and immunocytochemical studies of macrophages in an excitotoxin induced lesion in the rat brain. AB - An epidural application of kainic acid (KA) over the cerebral cortex in rat resulted in an extensive lesion in the ipsilateral cerebral cortex. This procedure elicited an accumulation of a large number of macrophages at the site of lesion covering a period of 4 weeks beginning 4 days after the KA application. The macrophages in the centre of lesion were characterized by abundant cytoplasm containing a variable number of lysosomes and phagosomes. Neurons at the same site were depleted during the period examined. They underwent degeneration following the KA treatment. With the monoclonal antibodies OX-42, OX-18 and OX-6, intense immunoreactivity was observed in these cells at the light and electron microscopic levels. Besides these antibodies, the cells were stained positively with the isolectin Griffonia simplicifolia (GSAI-B4). At the periphery of the lesion, many cells bearing the external morphology of microglia were also intensely stained with the GSAI-B4 and the monoclonal antibodies. It was concluded from this study that neuronal degeneration, caused by the excitotoxin KA, induced the accumulation of macrophages which exhibited CR3 receptors (marked by OX-42), MHC I antigen (marked by OX-18) and MHC Ia (marked by OX-6). The expression of these surface antigens may be related to their active phagocytic activity. The reaction with GSAI-B4 indicates the presence of specific lectin receptors on the macrophages which would serve a similar function. The present lectin histochemistry and immunohistochemical studies suggest that macrophages in the centre of the KA-induced lesion were derived from infiltrated monocytes while those at the periphery originated from the activation of local microglial cells. PMID- 1494043 TI - Parvalbumin in the medial septum/diagonal band complex of the African green monkey Cercopithecus aethiops. AB - The distribution of the calcium-binding protein Parvalbumin (PV), a marker for a subpopulation of GABAergic neurons, was studied in the septal complex of the African green monkey, Cercopithecus aethiops. PV-immunoreactive neurons were found in relatively small numbers in the medial septum and in large numbers in the nucleus of the diagonal band (BROCA). They were extremely rare in the dorsal and intermediate parts of the lateral septum. PV-immunoreactive neurons in the medial septum and the nucleus of the diagonal band were mostly fusiform when located close to the midline and round to polygonal in more lateral locations. Some perikarya of immunopositive as well as immunonegative cells were covered with immunostained boutons whereas others were not. Our present descriptive data suggest that there are no principal differences in PV-containing neurons in the septal region between non-human primates and rodents which have been analyzed in great detail in previous studies. PMID- 1494044 TI - [Quantitative analysis of lamina III pyramidal neurons in the parietal cortex of newborns]. AB - The stage of neuronal development in the parietal (postcentral) cortex of human newborns was studied quantitatively in postmortem cases of different gestational (37th or 40th week) and postnatal age (2 hours or 3 weeks). In GOLGI-impregnated tissue obtained by autopsy, layer III pyramidal neurons were investigated. Comparatively, data were collected about dendrite parameters such as dendritic branching, length and spine density. The spine distribution (number and density) at the apical main dendrite, the apical tuft dendrites and in single basal dendritic fields as well, typically for the human layer III pyramidal neuron at the end of the gestational period, is described. Dendritic parameters from basal dendritic fields were compared in the three cases investigated (37th week with 2 hours or with 19 days of survival; 40th week of gestation with 2 days of survival). The large increase in spine number and density, especially in the second and higher orders of dendritic branching was obvious in the 19 days old infant brain. Special pathological aspects of the cases influencing the neuronal development are discussed. By means of a computerized method, quantitative data characterizing the human lamina III pyramidal neuron at the end of gestation are provided. PMID- 1494045 TI - Development of the visual system of the chick--a review. AB - This article reviews recent and earlier findings that yield the present knowledge about the embryonic development of retina, tectum, and the retinotectal projection in the chick. Data and concepts dealing with cell proliferation, migration, and differentiation, the processes underlying the generation of cytoarchitecture in the nervous system are discussed for the avian visual system. Emphasis is also laid on the presentation of hypotheses and experiments about directed axonal growth along the visual pathway and concerning the mechanisms responsible for the establishment of specific connections between retinal ganglion cells and their central targets. Among the results, the following topics deserve special attention: 1) Investigations of morphogenetic factors in vitro, and the application of recombinant retroviruses in vivo to study cell lineages rendered new insights into the processes of cell determination and differentiation. The evolving picture in this progressing field is discussed. At present, however, the research of retinal and tectal histogenesis is still largely in the state of morphological description. 2) Both systems, retina and optic tectum, develop independently from each other but in corresponding spatio temporal patterns, which provide that ingrowing retinal axons encounter receptive target tissue at appropriate locations at the time when connections are due to be formed. 3) Possible mechanisms of directed fibre growth are being elucidated by increasing efforts in research devoted to cell surface molecules, neurotrophic, and inhibitory substances, and their receptors. The axons of the primary visual pathway seem to be guided by local cues on glial endfeet and perhaps in the extracellular matrix, but so far, instructive molecules to which functional significance can be assigned have eluded discovery. 4) The question, how the retinotopic projection upon the tectum is created during development, remains still unsolved, although most results point to modified forms of the chemoaffinity hypothesis for its explanation. Sequential maturation and growth, selective fasciculation of orderly entering axons, recognition of positional tectal markers, and functionally controlled refinement may together contribute to the correct retinotectal projection. PMID- 1494046 TI - Physicians, prophets, freedom, and justice. PMID- 1494047 TI - ECG of the month. One-sided affair. Complete right bundle branch block. PMID- 1494048 TI - Laryngeal papillomatosis. AB - The papilloma is one of the most common benign neoplasms of the larynx. Laryngeal papillomatosis is a disease of widespread papilloma formation that most commonly affects the larynx but may involve multiple areas of the aerodigestive tract. Typically, onset of disease during childhood is associated with much more aggressive disease. The etiology of this disease is the human papillomavirus. Diagnosis is often delayed because the symptoms mimic a variety of other diseases. Laryngeal papillomatosis can also be extremely frustrating to treat since the lesions are most often recurrent and aggressive. This article reviews laryngeal papillomatosis, its differential diagnosis, presentation, and classifications as well as its treatment past, present, and future. PMID- 1494049 TI - Socrates, Shakespeare, Sherlock Holmes and the history of medicine. PMID- 1494050 TI - Trauma care in Louisiana: problems and possibilities. AB - Trauma is a major national health problem and is the leading cause of death for Americans under the age of 44. Data about the impact of trauma in Louisiana is lacking and there are currently no statewide initiatives for improving trauma care. Louisiana State University Medical Center Hospital in Shreveport (LSUMCH) has recently been licensed and designated by the state as a "primary trauma center." Additionally, the city of Shreveport has enacted a trauma system which preferentially transports major trauma victims to LSUMCH. This is the only such center and system in the state. Based on this experience, it is suggested that development of a network of trauma centers utilizing the resources of the main state teaching hospitals may be a feasible means to upgrade and enhance trauma care in the state. PMID- 1494051 TI - The use of nonsteroidal anti-inflammatory medications: a therapeutic dilemma. AB - Nonsteroidal anti-inflammatory drugs are the mainstay of therapy for musculoskeletal disorders. Despite being effective for many people they may have serious side effects and their use should be carefully considered in some groups of patients. This article reviews basic information about nonsteroidals including usage, side effects, groups at high risk, and suggestions for decreasing toxicities. PMID- 1494052 TI - Atraumatic severe streptococcal axillary cellulitis. AB - Axillary streptococcal cellulitis is rare but has been known to clinicians for years. Usually associated with trauma, it may, however, occur in previously healthy individuals who for unknown reasons can be slowly responsive to appropriate antibiotics. PMID- 1494053 TI - Treatment of urinary incontinence in the elderly. AB - Urinary incontinence affects millions of American men and women. Treatment consists of drug therapy, exercises, mechanical devices, surgery, and injection therapy. This article reviews the advantages and disadvantages of all treatment modalities for this common medical problem. PMID- 1494054 TI - Raynaud's features in childhood. Clinical, immunological and capillaroscopic study. AB - Raynaud's phenomenon, uncommon in childhood, often heralds connective tissue disorder. Since microvascular abnormalities can be detected at an early stage of the connective tissue disease, especially in scleroderma, a specific diagnosis can be made in patients presenting with Raynaud's phenomenon alone or Raynaud's phenomenon associated with symptoms suggestive of connective tissue disease. Raynaud's phenomenon was studied in 11 consecutive children, 10 girls and 1 boy, ages 6 to 15. One child had a definite diagnosis of cutaneous polyarteritis nodosa. In 6 others connective tissue disease was suspected: 4 had arthritis, 2 has telangiectasia, leg ulcers and antinuclear antibodies. Of the remaining 4, one had hemiplegia and 3 Raynaud's phenomenon only. Oscillometry of the radial artery was reduced in 7 of 9. Decreased capillary resistance was found in 2 of 6, while abrupt thinning in conjunctival vessels was seen in 3 of 7. On nailfold capillaroscopy, reduced vascularity was noted in 5 of 11, dilated capillaries in 4 of 11, tortuousity in 2 of 11, capillary thinning in 1 of 11, capillary spasm in 1 of 11 and normal pattern in 3 of 11. Two patients presenting with Raynaud's phenomenon were found to have "scleroderma-like pattern" on nailfold capillaroscopy. One of them died 2 years later of cardiopulmonary sclerosis, and another developed esophageal stricture and Barrett's esophagus. Neither has sclerodermatous skin. In childhood Raynaud's phenomenon, nailfold capillaroscopy is a non-invasive examination enabling early diagnosis of "systemic scleroderma sine scleroderma". PMID- 1494055 TI - [Prospective etiologic study of 128 patients with ambulatory dep vein thrombosis]. AB - Etiology of deep vein thrombosis in ambulant patients (DVTA = TVPA in text) varies: cancer, blood disease, infectious focus, dysimmunity syndrome, dysglobulinemia, extrinsic compression, metabolic disorder, anomaly of hemostasis. A prospective study was carried out between June 1988 and September 1989 by angiologists in 5 regions of France to evaluate the diagnostic rentability of an epidemiologic survey and to determine possible distinctive characters of DVTA. The survey was comprised of a questionnaire, a full clinical examination and screening tests: chest x-ray, abdominopelvic ultrasound imaging, a-uro/gynecologic examination, full blood count, serum iron, ferritin, uric acid, triglycerides, cholesterol, protein electrophoresis, antinuclear antibodies, circulating anticoagulant, hemostasis factors and liver function tests. The study included 128 patients, mean age 60 +/- 16 years with a DVTA developing without a previous immobilization. The usual predominance in the left leg was not observed. The etiology was identified in 33 cases, including 20 (15.6%) as a result of the screening tests: anomalies of hemostasis (8), blood diseases (3), dysimmunity syndromes (4), extrinsic compression (3), cancer metastasis (1) and hypertriglyceridemia in a diabetic (1). The screening procedure was of no greater value in the absence of a triggering or predisposing factor, on the contrary. An anomaly of hemostasis was detected more frequently in the presence of local or regional triggering factors in the men (4 out of 4) and in the women on the pill (4 out of 4). The number of cancers discovered following screening (2%) was smaller than that expected according to the literature (10%).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1494056 TI - [Is it possible to cure various disorders of stability or vertigo by surgical correction of tight stenosis of a supra-aortic artery?]. AB - While the efficacy of vertebral arteries revascularisation on the symptoms of vertebrobasilar insufficiency (VBI = IVB in text) is well established, the effect of correction of stenosis of vessels other than the vertebral arteries on stability disorders and vertigo do not appear to have been studied to any extent. Furthermore, vertigo is not considered as specific to VBI. A retrospective study was therefore carried out to determine the outcome in 33 patients with static disorders or vertigo operated upon for a severe stenosis of a brachiocephalic trunk, a carotid artery or a subclavian artery, with or without associated stenosis of a vertebral artery which in all cases had been neglected. Two patients (6%) died during the early stages of this series. Mean duration of follow up was a little longer than 5 years. One month post-operation 61% of the survivors were asymptomatic, all the others reported marked improvement in their symptoms and all had resumed their social life. At a later stage two patients had a clinical relapse associated with new arterial stenosis. Findings in this small series suggest that it is possible to cure or improve patients with stability disorders or vertigo by the surgical correction of a severe stenosis of a supra aortic artery other than a vertebral artery. PMID- 1494057 TI - [Ambulatory and hemodynamic treatment of venous insufficiency (CHIVA cure)]. AB - Contrasting with the destructive methods of treating varicose veins, the CHIVA cure (Cure Conservatrice et Hemodynamique de l'Insuffisance Veineuse en Ambulatoire) technique is a conservative and hemodynamic approach of this problem. Based on coherent physiological principles, it proposes rigorous analysis followed by effective correction of the hemodynamic disorders, resulting in lasting benefits on the esthetic, functional and tropic changes associated with varicose veins. The results of the CHIVA technique in several french and european-centers, including over 10,000 procedures performed between 1987 and 1991, confirm the value of the method first described by the author in 1988. They confirm the necessity of respecting the strategic and tactical rules of this new approach and the need for specific theorical and practical training. PMID- 1494058 TI - [Ambulatory and hemodynamic treatment of varicose veins (CHIVA cure). Revolution or regression]. AB - Ambulatory Hemodynamic Treatment of Varicose veins (CHIVA), owing to duplex scan, is a come back to forgotten method of cutting and ligation of superficial veins which have for a long time given the proof of inefficiency. This method ignores the fundamental problems of venous insufficiency. The long dated superiority of this technic about venous preservation compared with other methods is not demonstrated. The analysis of recurrent varicose veins after surgical treatment shows that the main cause is an inadequate operative technique associated with the evolution of the basic wall failure. CHIVA-cure, starting from the opposite opinion is doing un unbelievable come back to staged ligation expecting better results. The high rate of superficial venous thrombosis and complementary acts on the residual varicose veins, only one year after the primitive surgery, don't augur well of the future. PMID- 1494059 TI - [Influence of arterial hypertension on diabetic retinopathy]. AB - In the industrialized countries, diabetic retinopathy represents the most frequent cause of blindness during the period of active life. It occurs as two distinct clinical entities: non proliferating retinopathy characterized by dilatation of the retinal capillary bed and alterations in their vascular wall responsible for an increase in permeability, and proliferating retinopathy characterized by the appearance of pre-retinal neovessels secondary to the presence of vast zones of retinal ischemia. Numerous risk factors are implicated in the development of diabetic retinopathy: the primordial factor is the optimal equilibration of blood glucose levels. The primum movens of these diabetic lesions could be intoxication of the pericipets and endothelial cells of the retinal capillaries by an accumulation of sorbitol and fructose in this region. Additionally, the hyperglycemia suppresses the functioning of the retinal blood flow feed back system. An increase in systemic blood pressure will therefore be transmitted directly to the damaged capillary bed. In type II diabetes (NID), worsening of the diabetic retinopathy correlates with elevation of the systolic blood pressure. In type I diabetes (ID), worsening of the diabetic retinopathy correlates with an elevated diastolic blood pressure. A diastolic pressure of less than 74 mm Hg is a statistically significant protective factor against the worsening of type I diabetic retinopathy. PMID- 1494060 TI - [Arterial hypertension and diabetic nephropathy]. AB - A high incidence of renal lesions is observed in patients with insulin-dependent diabetes. In the early stages of the disease glomerular capillary hemodynamics is altered with, in particular, glomerular hyperfiltration related to several factors: enhanced glomerular capillary flow rate, capillary hypertension and increased filtration area. These hemodynamic changes could affect development of the glomerular microangiopathy: the final outcome of this is the glomerulosclerosis associated with a progressively worsening and ineluctable chronic renal insufficiency. Hypertension, frequent in the early stages, is practically constant when the neuropathy stage has been reached; it is well established that hypertension accelerates the development of glomerular lesions and the progression of the renal impairment. Experimental and clinical studies have clearly demonstrated that antihypertensive treatment slows down the degradation of renal function. All antihypertensive drugs appear to be effective, but converting enzyme inhibitors, by their effects on renal hemodynamics, could play a particular role in the prophylactic treatment of diabetic nephropathy. Determination of urinary excretion of albumin (microalbuminuria), the global evidence of the onset of a nephropathy is useful for the follow up of the renal disease, allows follow up of the renal lesion and evaluation of the efficacy of treatment. PMID- 1494061 TI - [Compression of the left renal artery by the diaphragm]. AB - Investigation of hypertension in a 21 year old man detected the presence of stenosis of the left renal artery. The arteriographic appearance of this stenosis, associated with the presence of stenosis of the celiac trunk of identical morphology, was suggestive of extrinsic pressure by the diaphragm and excluded endoluminal dilatation. Section of the left diaphragmatic crus released the renal artery and celiac trunk with complete recovery from the hypertension. PMID- 1494062 TI - [Thrombosis, immunology and drugs]. AB - Diagnosis of thrombopenia due to heparin in sometimes false. We present a case with venous thrombosis in whom the suspicion of thrombopenia induced by heparin finally proved to be a quinidine induced lupus. Related to this observation we emphasise the importance of immunological investigation in patient with venous thrombosis. PMID- 1494063 TI - [Mountain frostbite. A new approach to early prognosis. A study of 1,267 cases]. AB - Regarding an important series of mountain frostbite (1,267 cas), the authors try to explain the physiopathological mechanism. They expose the different methods that make possible nowadays an early prognosis. They set forth the treatment that seems still limited to save what can be spared; and this is valid for severe frostbite, the only ones to put problems. The quick warming up is the keystone of the treatment. PMID- 1494064 TI - [Lipid balance in an arteritic patient and therapeutic implications]. AB - The pathogenesis of atherosclerosis remains hypothetical, the current vogue of a lipidic origin being now only a working hypothesis. The management of an arteritic patient (for a treating clinician) is that of a case of global atherosclerosis. Screening for lipids: 1) is here of only moderate interest in the close scrutiny of currently recognized risk factors, and 2) should include initially a simple study of total plasma cholesterol (TC) and triglycerides (TG) on two occasions at one month's interval in a reliable laboratory. Therapeutic implications are a function of a global analysis of the patient and not just the values for even sophisticated assays of circulating lipids. PMID- 1494065 TI - [Theoretical and practical bases of compression]. AB - The pressure applied by rigid or elastic compression of the skin surface of a limb is exerted as a function of two parameters. Pressure applied by an elastic tissue acts according to Laplace's law, varying with the tension of the elastic tissue and the radius of the curve of the area compressed. A rigid dressing acts solely by alternating working and resting pressures. Superficial pressure is transmitted to the extra- and intra-fascial compartments through the intermediary of an increase in tissue pressure. This pressure extension acts on all the compressible structures of the limb. It reduces the caliber of the veins in all compartments, and therefore the total venous blood volume of the limb, and increases the rate of circulatory return. The venous pressure adapts itself to the pressure of the dressing. The action on the vessel wall is seen as an increase in fibrinolytic activity and the proliferation of contractile myocytes. Its principal effect, however, is on vascular-tissue integrity: it diminishes interstitial edema and compacts the connective tissue fibrils, decongests the capillary endothelium and reduces the pericapillary sleeve of mucopolysaccharides. But it increases basal membrane thickness. Too high a pressure provokes collapse of the lymphangions. The rheologic action of the compression results in a decrease in blood viscosity. The effect of the compression is to induce local reabsorption of venous edema, while lymphatic edema is displaced towards the root of the limb to a zone where it may be reabsorbed. All these phenomena are reversible on removal of the compression treatment. PMID- 1494066 TI - Health services research. PMID- 1494067 TI - International efforts to measure health expectancy. PMID- 1494069 TI - Leukaemia clusters in Great Britain. 1. Space-time interactions. AB - STUDY OBJECTIVE: The aim was to test a large set of childhood leukaemia and lymphoma registrations for the presence of clusters in space and in time. DESIGN: The study was a space-time cluster analysis. SETTING: England, Wales and Scotland. PATIENTS: All registrations for leukaemia and lymphoma between 1966 and 1983 in children aged 0 to 14 years were examined. The records included date and age of registration, sex, diagnosis, and the map reference of the postcode of residence. Of the 9411 registrations, 8888 were suitable for inclusion. MAIN RESULTS: There was a statistically significant excess of case pairs occurring jointly within 0.5 km and 60 d of each other: 68 pairs compared with 50.0 expected. The excess was detectable in central England, in the north of England and Scotland, but not in the south west of England. It was concentrated within the age band 4 to 7 years and among the lymphatic leukaemias. Several potential artefacts were considered and excluded, but the possibility remained that clustered detections might be triggered by haematological examinations undertaken for some communicable disease. CONCLUSIONS: There was strong evidence of joint spatial-temporal clustering, with an excess of pairs separated by very short time and distance intervals. The causes are probably biological rather than artefactual, but further work will be necessary in order to exclude the latter. PMID- 1494068 TI - Body mass index and duration of breast feeding: a survival analysis during the first six months of life. AB - STUDY OBJECTIVE: The aim was to determine whether excess weight in lactating women is associated with earlier cessation of breastfeeding. DESIGN: The study was to prospective cohort analysis using a community sample of women. SETTING: Geelong the regional centre of the Barwon Region of Victoria, Australia, in 1984 85. SUBJECTS: All women who were breast feeding and whose first infant was born between 1 May 1984 and 30 April 1985 were asked to participate. Of these, 739 women participated, a response rate of 81%. MAIN RESULTS: Smoking, mother's age and occupation, the time the infant was first put to the breast, and mother's body mass index at one month postpartum all exerted statistically significant independent effects on the duration of breast feeding, assessed using Cox's proportional hazards regression modelling. The strongest effects were for smoking, with an adjusted relative risk for cessation of breast feeding of 2.5 (95% CI 1.9 to 3.1) for 10 cigarettes per day v no smoking, and maternal age, with relative risk of 2.2 (95% CI 1.5 to 3.1) for a 20 year old mother relative to a 30 year old. The relative risk for women with a body mass index above 26 was 1.5 (95% CI 1.1 to 2.0). CONCLUSIONS: Excess weight at one month postpartum, as determined by a body mass index above the normal range, was found to be an independent risk factor for early cessation of breast feeding and together with smoking, maternal age, occupation, and the time the infant is first put to the breast can be used to identify, early in the postpartum period, those women most likely to benefit from counselling in order to breast feed their infants successfully. PMID- 1494070 TI - Leukaemia clusters in Great Britain. 2. Geographical concentrations. AB - STUDY OBJECTIVE: The aim was to test a large set of childhood leukaemia and lymphoma registrations for the presence of short radius spacial clusters. DESIGN: The study was a geographical cluster analysis. SETTING: England, Wales and Scotland. PATIENTS: All registrations for leukaemia and lymphoma between 1966 and 1983 in children aged 0 to 14 years were examined. The records included date and age of registration, sex, diagnosis, and the map reference of the postcode of residence. Of the 9411 registrations, 8888 were suitable for inclusion. MAIN RESULTS: There was a significant excess of case pair addresses separated by < 0.5 km. There was also a significant excess of pairs sharing the same postcode. Both findings were based upon comparison with random pairs of postcodes drawn from the Central Postcode Directory. Examination for clustering at this very short range was based upon a clear prior hypothesis derived from the results of a study of space-time interaction, reported in a companion paper. CONCLUSIONS: It is postulated that the space-time interaction and the geographical concentrations shown here result from a common epidemic process. The epidemiology of this disease is characterised by short range geographical concentrations, with temporal non-homogeneity superimposed. The findings exclude certain artefacts which remained unresolved in the space-time interaction study. The distributions almost certainly reflect biological processes, and the most probable explanation is in terms of an infective process. PMID- 1494071 TI - Effect of subject age on costs of screening for colorectal cancer. AB - STUDY OBJECTIVE: The aim was to estimate costs and yields of faecal occult blood screening and rescreening for colorectal cancer, for differing age cohorts. DESIGN: Cost and clinical data were used as the basis for modelling the expected costs, and cost savings, resulting from the treatment of screen detected cancers, as compared with cancers detected by symptomatic presentation. SETTING: Data were derived from the MRC screening trial currently in progress in Nottingham. PARTICIPANTS: Approximately 140,000 subjects, age 50-79 years, were randomly allocated to a test (screened) and a control (unscreened) group. MAIN RESULTS: The net costs of detecting and treating a cancer following colorectal screening fall as the age of the target population increases, owing principally to the increasing incidence of the disease with age. Generally, the marginal detection and treatment costs falls for all age groups with the first screening round, but rises considerably with the second. If allowance is made for cancers prevented as a result of early detection and excision of adenomas, the costs of screening are substantially reduced for all age groups. CONCLUSIONS: Assuming a cost per QALY (quality adjusted life year gained) equivalent to that derived for the breast cancer screening programme, and a QALY gain from colorectal screening of one year, three screens, each separated by two years, appear economically justified for populations aged 60 years and above. Expected gains from cancer prevention make two screens justifiable for those between 45 and 59 years of age. PMID- 1494072 TI - A new approach to estimating AIDS incubation times: results in homosexual infected men. AB - STUDY OBJECTIVE: The aim was to develop a new approach for estimating the incubation period of acquired immunodeficiency syndrome (AIDS), based on age distributions. DESIGN: Incubation period was expressed as the difference between age at time of diagnosis and age at time of contamination. Assuming independence between age at time of infection and incubation period, the age distribution of newly diagnosed AIDS cases is thus the convolution product between the distributions of the age of freshly infected patients and of the incubation times. AIDS incubation time can therefore be estimated from the age distribution of newly HIV infected subjects and newly diagnosed AIDS cases. SUBJECTS: Subjects were 2220 AIDS cases diagnosed until 1987, reported to the Ministry of Health, France, and 172 subjects discovered to be HIV-1 seropositive during a blood donation in Paris between August 1985 and July 1988. In both groups, the only known risk factor was homosexuality. MAIN RESULTS: The estimated median incubation time was 9.9 years (90% CI 9.0-10.9 years). Confidence intervals were narrow, even when taking into account the uncertainty in serodetection delay (90% CI 6.7-13.5 years). CONCLUSIONS: The incubation estimate is as accurate as previous estimates based on other models. This technique could therefore be applied to other risk groups. PMID- 1494073 TI - Cost-benefit analysis of a nationwide neonatal inoculation programme against hepatitis B in an area of intermediate endemicity. AB - STUDY OBJECTIVE: The aim was to estimate the costs and benefits of a nationwide neonatal vaccination campaign against hepatitis B in Israel for the 1990-2034 period. DESIGN: Using morbidity, mortality, utilisation, and cost data from Israeli and international sources, a spreadsheet model was constructed to carry out the cost-benefit analysis. SETTING: The entire State of Israel, an area of intermediate endemicity. PARTICIPANTS: The population of Israel from 1990-2034. MAIN RESULTS: A policy of immunising all Israeli neonates would, for a cost of $13.8 million, reduce the number of cases of hepatitis B during the 1990-2035 period in the cohort from 359,000 to 166,000 and save the nation around $21.5 million in health resources alone, $16.6 million in averted work absences, and a further $0.6 million in averted premature mortality costs. Even when the savings to the health services ($0.6 million) arising from the reduction in hepatocellular carcinoma are excluded, the direct benefit to cost ratio is 1.51/1, still in excess of unity. CONCLUSIONS: The decision to adopt a nationwide neonatal inoculation policy, starting in January 1992, appears to be not only medically but also economically justifiable. PMID- 1494074 TI - Parity as a correlate of adult female urinary incontinence prevalence. AB - STUDY OBJECTIVE: The aim was to investigate the possible association between parity, as indicated by the number of childbirths, and prevalence of urinary incontinence in an adult female population sample. DESIGN AND SETTING: A sample of 3114 women aged 30-59 years was selected at random from the population of Aarhus, Denmark, and mailed a self administered questionnaire on urinary incontinence and, among other things, parity. PARTICIPANTS: A total of 2631 questionnaires was returned (85%) with a slight but significant decrease in respondency by age. MAIN RESULTS: The 1987 urinary incontinence period prevalence was 17%. Seventy eight percent were parous, and 24% had had three or more childbirths. In women aged 30-44 years, the prevalence of urinary incontinence was found to be associated with parity and, in women aged 45 years and more, with three or more childbirths. In parous women 30-44 years of age, the prevalence of urinary incontinence increased with age at least childbirth and, in women aged 45 years and over, it increased with increasing parity but decreased with increasing age at first childbirth. In parous women, no association was found with time since last childbirth. Among clinical types of urinary incontinence, stress incontinence consistently showed the strongest associations with indicators of parity. In women aged 30-44 years, nearly two thirds of the 1987 prevalence of stress incontinence could be attributed to parity. CONCLUSIONS: These findings support the hypothesis that pregnancy and childbirth are potent causes of female urinary incontinence, so that they exert considerable impact on the level of population urinary incontinence prevalence. In the individual woman, the effect seems to be cumulative and long lasting but fades with age. PMID- 1494075 TI - Mortality among female manual workers. AB - STUDY OBJECTIVE: The aim was to determine whether female manual workers have higher mortality than other women. DESIGN: This was a retrospective cohort study in which mortality was compared with that of the general female population. Main outcome measures were standardised mortality ratio (SMR) and 95% confidence intervals (CI). SETTING: Reykjavik region. PARTICIPANTS: Participants were 18,878 women, the cumulated members of a pension fund for manual workers between 1970 and 1986. MAIN RESULTS: A healthy worker effect was observed in the total cohort. The study was then restricted to those who had contributed to the pension fund any time after reaching 20 years of age, and a 10 year latency period was instituted. When analysing subcohorts by duration of employment the standardised mortality ratios for all causes of death and all cancers increased with longer employment time up to 10 years. However, the ratios were low in the group with over 10 years of employment. Those who began contributing to the fund in 1977 or later had higher mortality than those who began earlier. There was an excess of lung and bladder cancer in the total cohort and in all the subcohorts except in the group with over 10 years' employment. Mortality from accidents and suicides was in excess in all the groups. CONCLUSIONS: Mortality is high among some groups of female manual workers. A deficit was found among those with the longest employment. Differences in mortality have widened in recent years. An excess of suicides shows that women in this group have, for some reason, less will to live than other women. PMID- 1494076 TI - Effects of economic change on male morbidity in neighbouring industrial and rural municipalities in northern Sweden. AB - STUDY OBJECTIVE: The aim was to investigate the health effects of economic changes in a rural and industrial community. DESIGN: This was a historical cohort study with retrospective information on exposure and information on health outcome from a mailed questionnaire (response rate 82.5%). SETTING: An industrial and a rural community in northern Sweden. PARTICIPANTS: Participants included all men born in a rural community and a random sample of men born in a neighbouring industrial community 1915-1924 and alive in 1984 (N = 1989). MAIN RESULTS: Morbidity was higher in the cohort born in the rural municipality in which more profound changes in the socioeconomic structure had occurred. Even when taking such factors as childhood deprivation, migration, socioeconomic status, early retirement, unemployment, and single living into consideration, most of the differences in morbidity in the two municipalities still remained. However, the changes in employment conditions alone do not appear to explain the differences in morbidity that were found. CONCLUSION: The higher morbidity in the rural community indicates a health effect of the profound economic changes in that community but this difference cannot be explained by crude indicators of exposure to migration, unemployment, and other indicators of economic change. PMID- 1494077 TI - Regional differences in mental health in Great Britain. AB - STUDY OBJECTIVE: The aim was to study the pattern and magnitude of regional differences in psychiatric morbidity and compare these with regional differences in all cause mortality. DESIGN: The study was a secondary analysis of data from a cross sectional survey. The main outcome was the prevalence of psychiatric morbidity. This was assessed using the general health questionnaire, a self administered measure of neurotic symptoms. SETTING: England, Wales and Scotland. PARTICIPANTS: 9003 adults were selected from the electoral register. MAIN RESULTS: The prevalence of psychiatric morbidity was 31% with a statistically significant difference between the regions (p = 0.006). All four northern regions of England had a higher prevalence of psychiatric morbidity than the four southern regions. These differences were comparable in size to the regional differences in all cause mortality. Scotland had low psychiatric morbidity but high all cause mortality while Greater London had high psychiatric morbidity but low mortality. Regional variation in psychiatric morbidity was less marked within social classes I and II and among those living in urban areas. CONCLUSIONS: Psychiatric morbidity is common and is an important public health problem. Regions with relatively high psychiatric morbidity did not always have relatively high mortality. Knowledge of the causes of these regional differences could ultimately lead to preventive action and be important when distributing health service resources. PMID- 1494078 TI - Quality of life in the first 100 days after suspected acute myocardial infarction -a suitable trial endpoint? AB - STUDY OBJECTIVE: The aim was to determine the loss of quality of life following admission to hospital with suspected myocardial infarction. DESIGN: The study involved a cohort of admissions, with interview and follow up for 100 days. Main outcome measures were the quality of life prior to admission and at each stage of convalescence, estimated using the Rosser-Kind matrix: the calculated number of quality adjusted days during a 100 d follow up period. SETTING: The study took place in a teaching hospital in Scotland. PATIENTS: 206 patients were admitted with suspected acute myocardial infarction. Infarction was confirmed in 160 (Q wave infarcts 100, non-Q-wave infarcts 60), and unconfirmed in 46. MAIN RESULTS: The quality of life scores before the suspected heart attack were similar for patients whose final diagnosis was Q wave infarction, non-Q-wave infarction, or non-infarction. Of the 160 patients with confirmed infarction, only 54 (34%) had regained their previous quality of life scores at the end of 100 days, compared with 26 of 46 (57%) patients with unconfirmed infarction (p < 0.01). The mean numbers of quality adjusted days lost to patients with Q wave infarction, non-Q wave infarction, and non-infarction were 17.0, 12.4, and 5.9 respectively (infarction v non-infarction, p < 0.0001). Measurements of both quantity and quality of life contributed to these results. CONCLUSIONS: The number of quality adjusted days lost after acute myocardial infarction is a practicable measurement that is relevant to patients' lives. It might be suitable as an outcome measure for clinical trials of thrombolytic therapy. PMID- 1494080 TI - External validation, repeat determination, and precision of risk estimation in misclassified exposure data in epidemiology. AB - STUDY OBJECTIVE: The aim was to quantify the difference in precision of risk estimates in epidemiology between the situations where misclassification of exposure is corrected for by external validation and where it is corrected for by internal repeat measurement. Precision was measured in terms of the expected width of the 95% confidence interval on the odds ratio. DESIGN: In a hypothetical case-control study, first with 100 cases and 100 controls, then with 100 cases and 1000 controls (the latter to approximate the cohort study situation), expected estimated odds ratios and confidence intervals were calculated based on postulated underlying true odds ratios and misclassification error rates. The sizes of the confidence intervals using the two design strategies were compared, based on the same number of subjects receiving internal repeat measurements as were used in the external validation study. MAIN RESULTS: Confidence intervals obtained using internal repeat measurement were considerably narrower than those using external validation. Both methods yielded approximately correct point estimates. CONCLUSIONS: In terms of precision, it is preferable to correct for misclassification using internal repeat measurement rather than external validation. PMID- 1494079 TI - Baseline characteristics are not sufficient indicators of non-response bias follow up studies. AB - STUDY OBJECTIVE: The aim was to examine whether baseline characteristics from a cross sectional survey provided sufficient information regarding non-response bias in a follow up study when compared with information on hospital admissions in the intervening years. DESIGN: This was an 11 year follow up study of a cohort selected in 1974 with register information on hospital admissions during follow up. SETTING: The study was based on a sample of cement workers from a particular Portland cement factory with suitable controls from other occupations. PARTICIPANTS: A total of 1404 men participated in the first survey in 1974, including a questionnaire and lung function tests. In 1985 1070 men were alive and of these, 928 men (87%) responded to a postal questionnaire. MAIN RESULTS: Non-responders in 1985 did not differ markedly from responders when smoking habits, respiratory symptoms, and lung function were examined in 1974. During follow up, non-responders had twice as high rates of hospital admission due to respiratory diseases as responders. These differences remained present after adjusting for minor differences in age and smoking habits. CONCLUSIONS: Equal distributions of baseline characteristics among responders and non-responders in a follow up study do not preclude non-response bias. PMID- 1494081 TI - Standard assessment scales for elderly people. Recommendations of the Royal College of Physicians of London and the British Geriatrics Society. PMID- 1494082 TI - Predicting mortality from cervical cancer. PMID- 1494083 TI - Solving problems. PMID- 1494084 TI - Nursing diagnosis and obstetric, gynecologic, and neonatal nursing: breastfeeding as an example. AB - Nursing diagnosis is steadily gaining acceptance as the tool to use to communicate nursing's contribution to health care. Historically, however, obstetric, gynecologic, and neonatal (OGN) nurses have had difficulty applying the primarily problem-based diagnoses to a primarily well population. Two nursing diagnoses addressing breastfeeding have been accepted by the North American Nursing Diagnosis Association. The development and use of these diagnoses are discussed in this article. In addition, OGN nurses are challenged to develop other diagnoses that work within the OGN specialties. PMID- 1494085 TI - Pregnancy after perinatal loss: parental reactions and nursing interventions. AB - This article summarizes the recent literature on pregnancy after perinatal loss and suggests nursing practice strategies that can be used to assist parents experiencing such a pregnancy. It discusses problems with current theories, models of grief and mourning, and some common myths and applies Peretz's model of types of loss to a pregnancy loss. It describes, too, factors that influence parental response to grief and attachment and nursing interventions that may be appropriate when providing care during a pregnancy that follows perinatal loss. PMID- 1494086 TI - Helping infertile couples explore the option of adoption. AB - Adoption often is considered an ideal option for infertile couples. This article presents topics health-care professionals should address when discussing adoption with infertile couples and delineates interventions for anticipatory guidance once they decide to adopt. PMID- 1494087 TI - Moral decision making in neonatal intensive care. AB - OBJECTIVE: To gain information about the perspective that neonatal intensive-care unit nurses use to make moral decisions. DESIGN: Descriptive. SETTING: Neonatal intensive-care unit of a large teaching hospital in the midwestern United States. PARTICIPANTS: Convenience sample of 26 female nurses working in a neonatal intensive-care unit. METHOD: Audiotaped, semistructured interviews and demographic questionnaires. RESULTS: The results indicated that most (65%) of the nurses used the care perspective to make moral decisions. A small number (12%) used the justice perspective, and the remaining nurses (23%) used a combined care and justice perspective. CONCLUSIONS: Both the care and justice perspectives were found to be important for understanding how nurses make moral decisions. PMID- 1494089 TI - Social networks and help-seeking experiences of pregnant teens. AB - OBJECTIVE: To describe low-income pregnant teens' perceptions of their social network characteristics and their prenatal help-seeking experiences. DESIGN: Descriptive, cross sectional. SETTING: Prenatal clinic of an urban hospital (n = 29) and two other sites (n = 2). PARTICIPANTS: Thirty-one unmarried, low-income, pregnant teenage girls. MAIN OUTCOME MEASURES: Social network characteristics, including social support; relationships between social network characteristics and demographic variables; and help-seeking characteristics. RESULTS: Length of pregnancy was negatively correlated with network size (-.45, p = .011), emotional support (-.40, p = .026), tangible support (-.38, p = .033), and prenatal support (-.41, p = .022). Compared with older teens (18-19 years old), younger teens (16 17 years old) perceived their families, relatives, or both as providing a larger proportion of their total support (t(28) = 2.64, p = .014) and prenatal support (t(25.55) = 2.93, p = .007), and friends as providing a smaller proportion of their total support. Types of help most often needed were emotional and financial. The resource most used was the teen's mother, followed by the father of the unborn child. Barriers to help were most often the unavailability of someone on whom the teen relied and financial inadequacies. CONCLUSIONS: The perception of less support as pregnancy progresses may indicate a gap between needs and resources. Differences in younger and older teens' support sources and the focus of help seeking on emotional and financial support have implications for nursing care. PMID- 1494088 TI - Prenatal prediction of small- and large-for-gestational age neonates. AB - OBJECTIVE: To test the predictive accuracy of five fundal height growth curves in the identification of twin gestations and small-, appropriate-, and large-for gestational age neonates. DESIGN: Retrospective review of prenatal records. SETTING: Perinatal clinic at a tertiary-care center. PARTICIPANTS: Five hundred seven medically indigent women. MEASURES: Fundal height measurements were tested against the limits of normal for each week of gestation on five fundal height curves. Neonates were classified as small-, appropriate-, or large-for gestational age (based on weight for gestational age), except for twin gestations, which were classified as twins. RESULTS: The accuracy of the predictions depended on which curve was used and what criteria were used to classify fundal height measurements as abnormal. Small-for-gestational age neonates (n = 40) were correctly predicted in 27.5-70% of the cases, large-for gestational age neonates (n = 74) in 36.5-98.6% of the cases, and all four twin gestations. CONCLUSIONS: Clinicians should test the accuracy of any fundal height curve before using it in practice. PMID- 1494090 TI - The use of antibiotic-impregnated polymethylmethacrylate beads to prevent the evolution of localized infection. AB - The effect of antibiotic bead chains on the evolution of infection cannot be studied entirely in man due to the ethical problems of obtaining valid controls. Therefore, a model of musculoskeletal injury was devised in rabbits by making a paraspinal wound, fracturing a spinous process, and contaminating the wound with 1 x 10(4) colony-forming units/ml of Staphylococcus aureus. These contaminated wounds were treated with tobramycin-containing polymethylmethacrylate (PMMA) beads. Control rabbits were either treated with PMMA beads that did not contain antibiotic, treated with IM tobramycin, or left untreated. At 5 days, six of eight animals treated with antibiotic-impregnated beads had no recoverable organisms. Six of eight rabbits receiving IM tobramycin had wound infections, and five of five in whom non-antibiotic-containing beads had been implanted had significant wound infections, with one of the five dying of sepsis on the 3rd day of the experiment. The clinical course of infected controls was the same as the course of those animals receiving IM antibiotics and the same as those in whom beads without antibiotics were implanted. That is, the rabbits had grossly infected wounds and the organisms recovered were of the same type as those implanted. This research shows a highly statistically significant effect of tobramycin-containing antibiotic beads in retarding the evolution of an experimental Staphylococcus infection in rabbits. PMID- 1494091 TI - Comparison of closed reduction and percutaneous pinning versus open reduction and percutaneous pinning in displaced supracondylar fractures of the humerus in children. AB - A retrospective review of 29 children with displaced supracondylar humerus fractures was performed. Fifteen patients treated with closed reduction and percutaneous pinning and 14 patients treated with open reduction and percutaneous pinning were evaluated at a minimum of 18 months (range 18-80 months). Results were graded according to the criteria of Flynn et al. (Flynn JC, Matthews JG, Benoit RL: Blind pinning of displaced supracondylar fractures of the humerus in children. J Bone Joint Surg [Am] 56:263-272, 1974) using both cosmetic and functional evaluations. Excellent or good results were obtained in 14 of the 15 fractures treated with closed reduction and percutaneous pinning and in 12 of the 14 fractures treated with open reduction and percutaneous pinning. The three fair cosmetic results were associated with inadequate reduction and residual medial angulation. Ten to 15 degrees of motion loss occurred in three older patients. One patient in each group had a minor pintract infection. There were no cases of iatrogenic nerve injury or myositis ossificans. The treatment goal in displaced supracondylar humerus fractures in children is anatomic reduction. If an anatomic reduction cannot be achieved with closed reduction, open reduction is indicated. This can be done without an increased risk of complications. PMID- 1494092 TI - Closed reduction of mallet fractures using extension-block Kirschner wire. AB - Fourteen cases of mallet fingers with a displaced large fracture fragment and/or a subluxated distal phalanx were treated by closed reduction using extension block Kirschner wire. The follow-up evaluations took place after a mean of 9 months. The results according to Crawford's criteria were eight excellent, four good, one fair, and one poor. This technique is simple, is easier than other techniques for reduction of mallet fractures, and is associated with a low morbidity. PMID- 1494093 TI - The vertical axis fracture: a report on three cases. AB - We report on three cases of a rare fracture of the posterior body of C2. This is a variant of the classic traumatic spondylolisthesis and appears to respond to conservative management. PMID- 1494094 TI - Computed tomography-guided fixation of unstable posterior pelvic ring disruptions. AB - Open reduction and internal fixation (ORIF), the current treatment of choice of posterior pelvic ring disruptions with instability, has significant disadvantages. These include relatively "blind" placement of the fixation screws, infection, exsanguinating hemorrhage, and high wound complication rates. We feel fluoroscopy does not offer significant clarity in defining the posterior structure. Advantages of computed tomography (CT)-guided sacral fixation are direct visualization of the course of the screws and absence of significant wound complications. This technique provides superior visualization of the nerve roots and sacral canal compared to fluoroscopic methods. Thirteen patients (10 unilateral and 3 bilateral) with unstable but reducible sacral fractures or sacroiliac joint (SIJ) disruptions underwent CT-guided posterior pelvic ring fixation using a cannulated screw system. Skeletal traction was required intraoperatively in one case by a traction-counteraction pulley system in the CT scanner. All other reductions were performed by preoperative skeletal traction or manually by the surgeons after anesthesia in the scanner or after push-pull films demonstrated instability. The guide pin, using depth and angulation measurements derived from the scout CT scans, was positioned across the fracture or SIJ. Following CT confirmation of the position of the pin, the screw tract was drilled and the cannulated screw was placed into position. Radiographic and clinical follow-up observation (7-24 months) showed healing with no significant complications in all 13 patients. Computed tomography-guided sacral fixation is a safe alternative to ORIF in selected patients with reducible unstable pelvic fractures. PMID- 1494095 TI - Heterotopic ossification and other perioperative complications of acetabular fractures. AB - Thirty-eight operatively treated fractures of the acetabulum were evaluated retrospectively for perioperative complications. Functionally significant heterotopic ossification (Brooker class III or IV) developed in 23% of those patients who did not receive adequate prophylactic irradiation or indomethacin. Irradiation and indomethacin were effective in the prevention of severe heterotopic ossification. The development of severe heterotopic ossification (class III or IV) was associated with increased time from injury to operation. We conclude that prophylaxis against heterotopic ossification is warranted to decrease the incidence of this potentially preventable complication in patients who incur significant time delays prior to surgery. Other significant complications included avascular necrosis (26%), infection (13%), and neural injury (16%). Avascular necrosis developed in one patient who did not have a documented dislocation. PMID- 1494096 TI - Chronically unreduced traumatic anterior dislocation of the hip: a report of four cases. AB - Four cases of unreduced (2-11 months postinjury) anterior hip dislocation are reported. One public dislocation 2 months postinjury was treated by open reduction with a fair result. A unique case of iliac dislocation 11 months postinjury, overlooked due to an associated femoral shaft fracture, was treated by valgus/derotation osteotomy. Two obturator dislocations 7.5 and 9.5 months postinjury were treated by a subcapital osteotomy and displacement of the femoral neck into the acetabulum (modified excision arthroplasty). Both of these patients had fairly stable, painless, and mobile hips at 2.1 and 2.8 years follow-up. By our method, subsequent total hip arthroplasty remains a viable option, in contrast to the previously described method of trochanteric osteotomy, whereby the proximal femoral anatomy is distorted. PMID- 1494097 TI - Operative management of displaced femoral head fractures: case-matched comparison of anterior versus posterior approaches for Pipkin I and Pipkin II fractures. AB - Because of the controversy surrounding the selection of the surgical approach for the operative management of femoral head fractures, we retrospectively reviewed the combined experience with femoral head fractures at two major trauma centers. Forty-three femoral head fractures in 41 patients were identified. Twenty-six of the 43 fractures were Pipkin types I and II, and were managed operatively. Of the 26 patients, 12 with > 2 years of follow-up were managed with posterior surgical approaches and 12 with anterior surgical approaches. These patients were assessed with respect to operative time, estimated blood loss and function, and the radiographs for reduction, avascular necrosis, and heterotopic ossification. There was a significant decrease in operative time, estimated blood loss, and improved visualization and fixation with the anterior approach; however, there was a significant increase in functionally significant heterotopic ossification. The functional results in the two groups were identical; 67% good and excellent in each. There were no cases of avascular necrosis of the femoral head associated with an anterior approach. Because of the greater ease of access to the fracture, the anterior approach is recommended when operative reduction of a displaced Pipkin type I or II is indicated, but newer methods of minimizing heterotopic ossification must be developed. PMID- 1494098 TI - Femur fractures in alpine skiers. AB - From the years 1982 to 1989, 377 patients with alpine skiing-related injuries were admitted to St. Anthony's Hospital (a level one regional trauma center). Fifty femur fractures were recorded in 48 patients: 29 femoral shaft fractures (2 open), 15 hip fractures, and 6 supracondylar fractures (2 open). In the femoral shaft fracture group, the predominant fracture pattern was a short, transverse, comminuted fracture, illustrating the high kinetic energy of the accident. In this group, 11 patients returned to skiing, 7 of whom had hardware in place. Of the 10 Garden femoral neck fractures, 4 progressed to avascular necrosis. Three patients required press-fit total hip arthroplasties. Only 4 of these 10 patients returned to skiing. Median injury severity scores were 9.1 in 345 patients (94%), suggesting isolated trauma. Collisions with trees or poles accounted for 32% (15 patients) of all injuries. Follow-up data on return to skiing was available on 43 patients and of these 19 (44%) returned to skiing. PMID- 1494099 TI - Intramedullary nailing of the femoral shaft: a prospective, randomized study. AB - We conducted a prospective, randomized study on 84 consecutive patients with 88 acute, traumatic femoral shaft fractures using 32 Grosse-Kempf nails, 29 Russell Taylor nails, and 27 Synthes nails. Although total operative times and proximal and distal locking times were similar for the three groups, the procedure was faster with the Grosse-Kempf nail. Three proximal fractures could not be locked with the Synthes nail. At first follow-up, we found no significant difference in terms of pain, limp, range of motion, or time to union; however, we removed fewer Synthes nails to resolve patient complaints of pain. Three delayed unions were attributed to fracture distraction. We conclude that all three nails are suitable for the treatment of almost all femoral shaft fractures. A careful analysis of intraoperative technique and instrumentation indicates that all three nails can be used safely and easily once experience is gained. Clinical outcome is similar regardless of the nail chosen. PMID- 1494100 TI - Stabilization of pediatric diaphyseal femur fractures with flexible intramedullary nails (a technique paper). AB - The indications for surgical stabilization of a pediatric diaphyseal femur fracture are expanding. Children with multiple system injuries, a head injury, and/or multiple fractures have fewer local and distant complications if the femur fracture is treated operatively. Other indications include a pathological fracture in osteoporotic bone, a fracture in a child with a preexisting condition that prevents the application of a spica cast, a child older than 10 years of age, or a child less than 10 years of age who cannot be kept adequately aligned using conventional (traction/casting) methods of fracture management. Here we describe a technique of stabilizing pediatric diaphyseal femur fractures using flexible intramedullary nails (Ender). This technique can be used in children of all ages and with all patterns of diaphyseal fractures. PMID- 1494101 TI - Removal of intramedullary rods after femoral shaft fracture. AB - We are reporting a retrospective review of the removal of 60 intramedullary rods in 58 patients. All fractures had healed at the time of rod extraction. The implant was removed from 34 asymptomatic patients (36 femurs). Twenty-four patients (24 femurs) had preoperative symptoms attributed to the femoral rod. Fourteen patients had symptoms about the greater trochanter preoperatively, five patients had symptoms referable to the knee, and five had infections about the femoral implant. Problems encountered included broken rods in five femurs, one of which was not apparent on preoperative radiographs. There were six patients (six femurs) who required further hospital care for postoperative hematomas. The development of a significant hematoma was not related to the location of the fracture, the presence of interlocking devices requiring removal, the length of time since injury, the performance of this procedure as an inpatient or outpatient, or the presence or absence of a functional drain. Of the 10 patients (10 femurs) who had proximal heterotopic ossification Brooker stage 2 or greater, wound hematomas developed in four patients (40%). There were no refractures. Although there may be an indication for rod removal, we do not recommend the procedure in asymptomatic patients. PMID- 1494102 TI - Tension band fixation of medial malleolus fractures. AB - A prospective study on tension band fixation of medial malleolus fractures was performed on 30 consecutive patients with 31 fractures from October 1987 until December 1990. All patients had at least a displaced medial malleolus fracture unreduced by closed methods. The fractures were classified into small, medium and large using a modified Lauge-Hansen classification. There were no nonunions or movements of wires postoperatively and only two patients had subjective complaints with reference to the wires that required hardware removal. There was one 2-mm malreduction and one patient with a wound slough and subsequent osteomyelitis. One fragment had 2 mm of displacement after fixation but went on to union. A biomechanical study was undertaken to compare fixation of the medial malleolus with K wires alone, K wires plus a tension band, and two cancellous screws. The tension band fixation provided the greatest resistance to pronation forces: for times stiffer than the two screws and 62% of the intact specimen. Tension band fixation of the medial malleolus is a biomechanically strong and clinically acceptable method of treatment for displaced medial malleolus fractures. This method of fixation may be especially useful for small fragments and in osteoporotic bone. PMID- 1494103 TI - Compartment syndrome of the lower limb caused by a tourniquet: a report of two cases. AB - Two patients sustained a severe compartment syndrome of the lower limb after surgery under bloodless field for 1 h 25 min and 43 min and with a tourniquet pressure of 350 and 450 mm Hg, respectively. In both cases fasciotomies were performed as an emergency procedure shortly after the initial operation. Renal failure was avoided but functional deficiencies, peroneal weakness, and restricted movements of the ankle resulted in both cases. We conclude that when using a tourniquet, any pre- and postoperative swelling or stiffness of the muscles in the operation area should be noted, even if the recommended time or pressure limits are not exceeded. Immediate fasciotomies of the affected compartments should be considered if the diagnosis is suspected. PMID- 1494104 TI - In vitro and ex vivo Ca-antagonistic effect of 2-methoxyethyl(E)-3-phenyl-2 propen-1-yl(+/-)-1,4-dihydro-2,6-dimethyl- 4-(3- nitrophenyl)pyridine-3,5 dicarboxylate (FRC-8653), a new dihydropyridine derivative. AB - The characteristics of calcium antagonism and vascular effect of 2 methoxyethyl(E)-3-phenyl-2-propen-1-yl(+/-)-1,4-dihydro-2,6-dime thyl-4-(3- nitrophenyl)pyridine-3,5-dicarboxylate (FRC-8653) were investigated. FRC-8653 inhibited an increase in intracellular free calcium concentration during membrane depolarization in PC12 cells. FRC-8653 also inhibited the specific binding of 3H nitrendipine to cardiac membranes, in a similar manner to nifedipine and nicardipine. FRC-8653 inhibited KCl- and CaCl-induced contractions in isolated rabbit aorta, but failed to affect norepinephrine-induced contraction. The vasorelaxing effect of FRC-8653 in rabbit aorta developed more slowly than those of nifedipine and nicardipine. In ex vivo experiment, the inhibitory effect of orally administered FRC-8653 against KCl-contraction in rat aorta lasted longer than that of nifedipine. These findings suggest that FRC-8653 dilates blood vessels by blocking calcium influx via dihydropyridine-sensitive, voltage dependent calcium channels and that the vascular effects are slow in development and long in duration. PMID- 1494105 TI - Influence of para substituent of phenol on phospholipid dependence of uridine diphosphate-glucuronyltransferase. AB - The influence of para substituent of phenol on the property of phospholipid dependence of uridine diphosphate-glucuronyltransferase (UDPGT) was studied using hepatic microsomes of the rats. para Substituents used were p-ethyl, p-tert-butyl and p-phenyl. Glucuronidations of phenol and its derivatives were inhibited with each other. When phospholipids of the microsomes were removed with phospholipase A2, Vmax and Km decreased in the order phenol, p-ethylphenol, p-tert-butylphenol, p-phenylphenol, indicating that this change by delipidation increased with van der Waals volume (Vw) of para substituent. Arrhenius plots of glucuronidation for phenol and p-ethylphenol exhibited a change in slope, responding to thermotropic property of the membrane labelled with 1,6-diphenyl-1,3,5-hexatriene (DPH). In contrast, p-tert-butyl and p-phenyl substituents showed linear Arrhenius plots. The activation energy (Ea) for glucuronidation of p-phenylphenol was increased by delipidation, whereas Ea of other substrates did not show any remarkable change. PMID- 1494106 TI - An enzyme immunoassay for cell proliferation using monoclonal antibodies directed against a cell proliferation-associated antigen. AB - An enzyme immunoassay (EIA) for assessment of cell activation and proliferation was developed by the use of monoclonal antibodies (MoAb) directed against a ubiquitous growth-associated antigen, gp125. Test cells distributed in a microtest plate were labeled with anti-rat gp125 MoAb, B3, for rat cells or anti human gp125 MoAb, HBJ127, for human cells and subsequently with rabbit anti-mouse immunoglobulins. The cell-bound antibody was assessed by a colorimetric enzyme assay using horse-radish peroxidase-modified protein A and 2,2'-azinobis(3 ethylbenzthiazoline sulfonic acid). To terminate the reaction and to make the reaction mixture transparent, sodium dodecyl sulfate (SDS) was added to the mixture. The intensity of the developed color was measured by use of a multiwell scanning spectrometer. The titration curves obtained by the EIA for cells were practically similar to those obtained by the conventional 3H-thymidine (Tdr) uptake method, and the appropriate cell number to be used for the assay was indicated to be 3 to 50 x 10(3) cells per well. This method was applicable not only for quantitation of cell number of growing cells but also for measuring mitogenic responses of lymphocytes as revealed by the data obtained from Con A stimulation of lymphocytes. These results indicate that this new EIA method using anti-gp125 antibodies is useful for quantitative assays of cell growth and cell activation in the research fields of oncology and immunology. PMID- 1494107 TI - Hypocholesterolemic effect of ursodeoxycholylcysteic acid in hamsters fed a high cholesterol diet. AB - We studied the effect of feeding ursodeoxycholylcysteic acid, the cysteic acid conjugated analog of ursodeoxycholyltaurine, on serum and liver cholesterol levels and on intestinal absorption of cholesterol and bile salts in hamsters. Addition of ursodeoxycholylcysteic acid to the cholesterol-enriched diet reduced the elevation of serum and liver cholesterol levels caused by feeding cholesterol. However, supplementation with ursodeoxycholylcysteic acid to the standard diet did not show any significant change in serum and liver cholesterol levels. Administration of ursodeoxycholylcysteic acid caused a decrease in dietary cholesterol absorption but did not interfere with the ileal transport of endogenous bile salts. Hence the hypocholesterolemic activity of dietary ursodeoxycholylcysteic acid is thought to be the effect on intestinal absorption of cholesterol but not to be the interruption of the enterohepatic circulation of bile salts. PMID- 1494108 TI - Study of interaction of pranoprofen with human serum albumin: binding properties of enantiomers and metabolite. AB - The interaction of pranoprofen, pranoprofen glucuronide and pranoprofen methylester with human serum albumin (HSA), was investigated by equilibrium dialysis and spectroscopic techniques. The binding affinities of pranoprofen glucuronide and pranoprofen methylester to HSA were found to be almost the same, although they were remarkably small as compared to that of the parent compound, pranoprofen. Pranoprofen and pranoprofen methylester showed stereoselective affinities to HSA. It was found from the competitive displacement experiments using the fluorescent probes that the specific binding site for pranoprofen was site II, the diazepam site, and that the binding sites of pranoprofen glucuronide and pranoprofen methylester were site I, the warfarin site. In addition, from the binding data with modified HSA, it seemed that tyrosine-411 was specifically involved in the pranoprofen binding. The absorption spectral changes which accompanied the binding of pranoprofen and pranoprofen methylester to HSA or detergents implied that the HSA binding site of pranoprofen consisted of a cationic site on the surface of the albumin molecule with a hydrophobic region to accommodate the aromatic ring and that the binding site for pranoprofen methylester seemed to occupy a wide hydrophobic area. These limited data indicated differences in the location and microenvironments of binding sites for pranoprofen and its glucuronide on the HSA molecule. PMID- 1494109 TI - [Dielectric analysis of the rat thyroid gland by modeling the follicle as a key structure]. AB - To correlate the dielectric behavior of the thyroid gland with its follicle structure, I examined the admittance properties of isolated rat thyroid hemilobes over the frequency range from 100 Hz up to 500 MHz. Rats were divided into three groups: control, thyroxine (T4) administered, and goitrogen (propylthiouracil, PTU) administered. In control glands, observed dielectric dispersions with a permittivity increment (delta epsilon) of 60,000 were of the beta-type having two separate characteristic frequencies (fc1 and fc2) around 12 kHz and 3 MHz. In T4- or PTU-treated thyroid, both delta epsilon and fc1 departed from those of control, resulting in the following sequences: For delta epsilon, T4 < control < PTU, and for fc1, PTU < control < T4. These contrasting results were then correlated with morphological features involved. Histomorphometry revealed apparent differences in follicular size distribution between the three groups of tissue. Based on a model analysis using curve fitting technique, I estimated the electrical conductivity of colloid to be about 2 mS/cm, a value 6-fold smaller than that of blood plasma. Another conclusion worthy of note is that the gross dielectric behavior of the thyroid gland can be interpreted only by taking the follicular structure into account. PMID- 1494111 TI - Compression resistance of four interocclusal recording materials. AB - Elastomeric impression materials are popular for making interocclusal records to mount casts on dental articulators. The resistance of these materials to compressive forces is critical, because any deformation during the recording or mounting process could result in inaccurate articulation of casts and faulty fabrication of restorations. This investigation compared the deformation of designated thicknesses (2 mm, 5 mm, 10 mm, and 20 mm) for four elastomeric interocclusal recording materials (Blu-Mousse, Stat BR, Ramitec, and Regisil) when subjected to a 25 N compressive load. Compressive distortions of clinical significance were recorded for all of the materials with various thicknesses. The Blu-Mousse vinyl polysiloxane registration material exhibited the greatest resistance to compression for the designated thicknesses, and these resistance values were significantly lower than those of the other recording materials with thicknesses of 5, 10, and 20 mm (alpha < 0.05). PMID- 1494110 TI - Use of dental implants in the treatment of patients with scleroderma: a clinical report. PMID- 1494112 TI - Stresses induced by different loadings around weak abutments. AB - Stresses and deflections of abutments induced by various loadings were analyzed with a two-dimensional finite element model. The biomechanic system consisted of the mandibular posterior three-unit fixed partial denture (FPD). Four different loading types were analyzed: (1) a distributed force of 600 N; (2) concentrated nonaxial and (3) axial 300 N forces at the marginal ridge of the molar; and (4) a concentrated vertical 300 N force at the center of the pontic. All computations were conducted for three different alveolar bone levels. The premolar exerted a greater pressure during occlusal loadings (except axially) on the alveolar bone than the molar. According to the stresses induced in the alveolar bone, the most critical loading was the distributed force. With diminishing periodontal support, stresses elevated in the biomechanic system and critical increases were noted for the concentrated nonaxial load on the molar. PMID- 1494113 TI - Use of luting agents with an implant system: Part II. AB - The purposes of this study were to determine the amount of die space necessary to reduce seating discrepancies of castings cemented onto implant abutments and to determine the effect that this space created for the luting-agent has on crown retention. Noble metal castings were made with 0.000 inch, 0.001 inch, 0.002 inch, and 0.003 inch spacing for premanufactured titanium implant abutments. The castings were cemented onto the abutments with three permanent luting agents. Seating discrepancies of each casting/abutment combination were measured, and the castings were pulled from the abutments by use of tensile force. The results of this study indicate that the use of die spacing decreased seating discrepancies and increased retentive values under the test conditions. PMID- 1494114 TI - Sealing effectiveness of light-cured glass ionomer cement liners. AB - Glass ionomer materials have been used as liners or bases beneath restorations, but light-cured varieties have recently been introduced. Microleakage at the restoration/tooth interface in cervical cavities was used to test the adhesion to dentin of two new light-cured glass ionomer cement lining materials, XR-Ionomer and Fuji Lining LC. Wedge-shaped cervical cavities were prepared on extracted teeth with a gingival cavosurface margin involving dentin, and the specimens were assigned randomly to three groups. The experimental groups were restored with two light-cured glass ionomer cements, the controls were restored with a chemically cured glass ionomer cement; and marginal leakage was assessed by dye penetration. The two light-cured glass ionomer cements displayed some adhesion to dentin in class V test cavities, but there was no significant difference between the two materials. PMID- 1494115 TI - Retention properties of a split-shaft threaded post: cut at different apical lengths. AB - The retention of the post to the root of an endodontically treated tooth is critical for a successful restoration. Modification of the post length to accommodate a specific clinical situation is common. This study compared the retention of No. 1 and No. 2 Flexi-Post restorations shortened apically from 1 to 5 mm with that reported for full-length control No. 1 and No. 2 Flexi-Post dowels. The experimental material was divided into 10 groups with 10 samples in each group. Retentive values were recorded in pounds with a universal testing machine. Analysis of variance with a Tukey-Student range, multiple-comparison test showed no statistical differences from apical reductions of 1, 2, 3, and 5 mm including the full-length control Flexi-Post No. 1 system. With 4 mm of apical shortening statistically greater retention was recorded. No statistical differences resulted with apical reductions of 1 to 4 mm or with the full-length control Flexi-Post No. 2 system, but 5 mm of apical shortening caused significantly less retention. PMID- 1494116 TI - The resistance to tensile, compression, and torsional forces provided by four post systems. AB - This study measured the force required to displace four different endodontic posts (an experimental, Para-Post, Flexi-Post, and V Lock) when tensile, torsion, or compressive forces were applied. Extracted mandibular premolars were decoronated at the cementoenamel junction, the roots were divided into groups of similar size, and the pulpal tissue was removed. The canals were enlarged, cleaned, and filled with gutta percha. Post preparations were made, and the posts were cut and cemented into the post spaces with resin cement. The roots were notched with a separating disc and lowered into a metal tube filled with acrylic resin. Two Minim pins were placed into the coronal dentin paralleling the post. Composite resin cores were made around the coronal 4 mm of the posts and the two pins for 10 specimens from each group. The specimens were placed into a standardized fixture and a load applied until failure. The tensile load required to pull the experimental post and resin was significantly less than the load required to remove the threaded posts. Flexi-Posts provided the greatest resistance to torsion and tensile loading. The compressive load required to fracture the core over the V-Lock post was significantly greater than the other post systems. PMID- 1494117 TI - Comparison of the shear bond strength of a titanium composite resin material with dentinal bonding agents versus glass ionomer cements. AB - This study compared the in vitro shear bond strength of an autopolymerizing composite resin system (CR) (Ti-Core) with two third-generation dentinal bonding agents (DBA) (Tenure and Scotchbond 2) to glass ionomer cements (GIC) (Ketac Silver, GC Miracle Mix, and Ketac-Cem). The experiment was divided in five groups. The shear bond strengths were evaluated on a universal testing apparatus at three different intervals; 15 minutes, 24 hours, and 7 days. Statistically, (two-way analysis of variance), the shear bond strengths from the greatest to least were: Ti-Core CR with Tenure DBA > Ti-Core CR with Scotchbond 2 DBA > Ketac Silver GIC, GC Miracle Mix GIC > Ketac-Cem GIC. There were no differences in shear bond strengths according to time, and no interactions between groups and time. The shear bond strengths for Tenure DBA with Ti-Core CR were two and a half to three times greater than the silver-filled glass ionomers, Ketac-Silver GIC and GC Miracle Mix GIC. Tenure DBA with Ti-Core CR also had consistently greater shear bond strengths than Scotchbond 2 DBA with Ti-Core CR, and this trend is in agreement with similar research. PMID- 1494118 TI - Retentive properties of threaded split-shaft posts with titanium-reinforced composite cement. AB - The retention of posts in tooth roots is vital to the success of the restoration. This study compared the retention of posts of various sizes and diameters cemented with a titanium-reinforced composite cement with that of posts previously reported cemented with zinc phosphate cement. Four groups made up of 10 samples each were used and retention values were compared using a universal testing machine. Two-way analysis of variance and the Newman-Keuls multiple range comparison test were performed. Larger diameter posts cemented with titanium cement had better retention than similar posts cemented with zinc phosphate cement. The statistical increase in retention for the larger size posts is probably the result of the deeper channels (threads) in the dentin and the higher cohesive strength for the titanium-reinforced composite resin. PMID- 1494119 TI - Endodontic dowel retention with resinous cements. AB - This study compared the capability of three composite resin cements to sustain a standard endodontic dowel. All of the systems incorporated some form of smear layer removal on the dentin of the endodontic channel. One system that used a methyl ethyl ketone drying agent provided inadequate clinical resistance to dislodgment of 5.4 DaN. A second cementing system that used only smear layer removal resisted loads at 54.7 DaN. The third cementing regimen that included a surface-initiated dentinal adhesive and smear layer removal recorded retention of 77.4 DaN. This study supported the concept that passively cemented dowels with composite resin can be as effective as actively seated dowels. PMID- 1494120 TI - Masticatory function in patients with extensive fixed cantilever prostheses. AB - Eleven patients with complete maxillary dentures and 12-unit fixed partial dentures that included the mandibular canines were studied before and during specific intervals after prosthodontic treatment. Established methods for evaluation of oral function were used and the last examination was performed 30 months after treatment. All patients reported that their masticatory function had been substantially improved and there were no symptoms of dysfunction in the masticatory system. Masticatory efficiency improved after the prosthodontic treatment because both the number of cycles before the initial swallow and the total number of strokes including the time for completed mastication diminished after treatment. The occlusal force elevated after the prosthodontic treatment. Although great individual variations were recorded for all occasions and force levels, forces recorded on the extensions of the cantilever were similar to those on the canine regions. PMID- 1494121 TI - The tooth-removable partial denture interface. AB - During the metal finishing phase of removable partial denture construction, metal is removed from all aspects of the casting. The amount removed from areas designed to contact prepared surfaces of abutments is critical to the resulting fit of the partial. Castings were evaluated before and during finishing procedures to measure metal loss at the tooth-removable partial denture interface. Finishing and fitting techniques for controlling the loss of metal are presented. PMID- 1494122 TI - The effect of reducing the number of clasps on removable partial denture retention. AB - Retention to a master model of 10 nominally identical chrome-cobalt removable partial denture castings with standardized bilateral molar and premolar clasps engaging 0.25 mm (0.01 inch) undercuts and 10 castings with clasps engaging 0.5 mm (0.02 inch) undercuts was measured on an Instron testing machine. The retention of each framework was remeasured as the clasps were removed in one of two sequences. Differences between frameworks, number of clasps, and depth of undercuts were all significant. The order of removal of the clasps was not statistically significant. In a separate experiment the position of the dislodging force was found to be significant. It was concluded that the dislodging force was dependent on (1) the fit of the framework, (2) the depth of the undercut, (3) the number of clasps, and (4) its point of application. PMID- 1494123 TI - Reinforcement of complete denture bases with continuous high performance polyethylene fibers. AB - Clinical literature details the causes for deformation and failure of acrylic resin complete denture bases. These findings are used to select patterns of high performance polyethylene fiber reinforcement that would best use the properties of the material and improve the mechanical behavior of the prostheses. A technique is described for making reinforced maxillary and mandibular bases with the fibers placed as suggested by the analysis. Microscopic observations of cross sections of reinforced bases revealed good fiber/resin integration and polish. PMID- 1494124 TI - A technique for fabrication of interim midfacial prostheses. AB - The interim midfacial prosthesis uses a rigid backing support with flexible margins and can be made with most types of commercially available medical grade silicone elastomers. The technique may be modified for fabrication of definitive midfacial prostheses. The disadvantage of the technique is that an extra step is required to make a duplicate master cast, and a vacuum adaptor is needed. PMID- 1494125 TI - Mechanical behavior of three maxillofacial prosthetic adhesive systems: a pilot project. AB - The use of maxillofacial prosthetic adhesives remains controversial. A new machine for mechanical testing of adhesives was developed. This machine was used for in vivo testing of three adhesive systems to determine the adhesive joint strength of bonding silicone facial prosthetic elastomer to facial skin. Tensile, torsion, and combined tensile-torsion tests were carried out on two human subjects. The three adhesives tested were PSA1, Pros-Aide, and Dow Corning 355. All adhesives were applied according to the manufacturers' instructions. A 900 gm bonding load was applied for 20 seconds. The experimental design made use of two subjects, and the entire experiment was repeated on each subject. One test site on the cheek was used. Adhesive types were compared by means of the Student Newman-Keuls method. Within the limitations of the design of this pilot study, the results showed that Dow Corning 355 adhesive was statistically significantly stronger than the other two adhesives evaluated by means of tensile and combined tensile-torsional tests. Although the results of the present pilot project are of interest, extrapolation to definitive conclusions of a clinical nature should be avoided. PMID- 1494126 TI - A study of 589 consecutive implants supporting complete fixed prostheses. Part II: Prosthetic aspects. AB - In 91 consecutive edentulous patients, 103 jaws were treated with complete fixed prostheses supported by Branemark Implants (n = 589). As a result of fixture loss in each of two patients (two jaws), an overdenture instead of a fixed prosthesis was installed. For one patient (two jaws), data were not available after abutment connection. At the end of the seventh year, the cumulative failure rates for the remaining 99 prostheses reached 4.9% for mandibles and 10.1% for maxillae. After loading, 12 fixtures showed signs of nonintegration, but only one patient had to revert to complete dentures. Neither the fixture location nor the cantilever length revealed a significant difference in marginal bone loss around the supporting fixtures. Patients with fixture-supported fixed prostheses in both jaws showed significantly more marginal bone loss than did those with only one fixed prosthesis opposed by either natural dentition (50%) or a complete denture (50%). Component complications were limited to fixture fracture (3/564), abutment screw fracture (5/564), and gold screw fracture (7/564). The predictability of Branemark implants in the treatment of completely edentulous jaws is confirmed. PMID- 1494128 TI - Effect of altered occlusal guidance on lateral border movement of the mandible. AB - The purpose of this study was to evaluate the effects of a change in the lateral anterior guidance pathway on the lateral border movement pathway of mandible. The results showed that altered occlusal guidance reproducibly and reversibly changed (increased) the lateral border movement area in two subjects who had unilaterally restricted lateral border movements. PMID- 1494127 TI - Occlusal adjustment therapy for craniomandibular disorders: a clinical assessment by a double-blind method. AB - Fifty-one patients with craniomandibular disorders were divided in two groups. One group underwent mock occlusal adjustment, the other was treated with adjustments to remove significant slides and non-working side interferences. Both groups received identical counseling. The results show that there was no significant difference in the improvements on the signs and symptoms obtained by real or mock adjustments after the first treatment session. PMID- 1494129 TI - The informed consent treatment report. AB - A brief history of informed consent and introduction of the "Informed Consent Treatment Report" (ICTR) is presented. The ICTR is a document developed in 1984 that combines the requirements of informed consent and the elements of good treatment planning and presentation to achieved improved patient and practice management. An outline of the parts and sections of the ICTR is included as a guide for preparing an informed consent and treatment planning document. PMID- 1494130 TI - Developing a workable infection control policy for the dental laboratory. AB - An enforced infection control policy in a laboratory will reduce occupational exposure to blood-borne pathogens and other infectious diseases and protect the dental laboratory personnel from exposure to infective disease. An outline of a workable laboratory infection control policy based on "Occupational Exposure to Bloodborne Pathogens" requirements is presented. PMID- 1494131 TI - Index to reposition the metal framework accurately on the altered cast. AB - The relieved portion of a master cast below the major connector of a cast removable partial denture framework can be filled with dental stone to act as a third point of reference when the framework is reseated in an altered cast procedure. With this simple procedure, an index is formed that will allow accurate repositioning of the metal framework on the altered cast. PMID- 1494132 TI - Replace axis-orbital pointer with level pointer in facebow transfer. PMID- 1494133 TI - No muss, no fuss irreversible hydrocolloid impressions. PMID- 1494134 TI - Polyvinyl siloxane as a disclosing medium. PMID- 1494135 TI - Implant denture modification with light-activated denture resin. PMID- 1494136 TI - Edentulous position of the temporomandibular joint. PMID- 1494137 TI - Common principle of guidance by echolocation and vision. AB - 1. Using echolocation, bats move as gracefully as birds through the cluttered environment, suggesting common principles of optic and acoustic guidance. We tested the idea by analysing braking control of bats (Macroderma gigas) flying through a narrow aperture with eyes covered and uncovered. 2. Though braking control would seem to require rapid detection of distance and velocity and computation of deceleration, simpler control is possible using the tau function of any sensory variable S that is a power function of distance to aperture. Tau function of S is tau (S) = S/S (the dot means time derivative). Controlled braking is achievable by keeping tau (S) constant. 3. Previous experiments indicated the tau (S) constant procedure is followed by humans and birds in visually controlling braking. Analysis of the bats' flight trajectories indicated they too followed the braking procedure using echolocation. 4. The tau function of echo-delay or of echo-intensity or of angle subtended by directions of echoes from two points on the approach surface could be used to control braking. Aperture size was modulated during flight on some trials in an attempt to test between these possibilities, but the results were inconclusive. PMID- 1494138 TI - Processing of frequency-modulated stimuli in the chick auditory cortex analogue: evidence for topographic representations and possible mechanisms of rate and directional sensitivity. AB - Responses of units in the auditory forebrain (field L/hyperstriatum ventrale complex) of awake domestic chicks were studied to frequency-modulated (FM) signals and isointensity tone bursts, presented to the ear contralateral to the recording sites. FM signals, linear frequency sweeps in the range of 50 Hz to 10.25 kHz, differed in the rate of change of frequency (RCF) and in the direction of modulation. The majority of RCF response functions obtained could be classified as predominantly ascending and bell shaped. Best rates of change of frequency (BRCFs), assigned to these functions, covered a range of nearly 3 orders of magnitude. BRCFs of the same units for upward (positive BRCFs) and for downward modulations (negative BRCFs) were correlated. The lowest BRCF encountered among all units for a given isointensity ON-response bandwidth (delta FON) increased as a function of delta FON. delta FON was derived from the responses to tone bursts of various frequencies at 70 dB SPL. As delta FON tended to increase with the best frequency (BF) of units the lowest BRCF encountered among all units for a given BF also increased as a function of BF. Positive and negative BRCFs of a unit were also correlated with the slopes of onset latency frequency relationships below and above BF, respectively. FM responses were optimal, when the frequency-specific latency differences at a given unit were compensated by the direction and rate of frequency change in the signal. FM directional sensitivity varied with BF. Most units with BFs below about 2 kHz preferred upward modulations, while those with BFs above 2 kHz preferred downward modulations. Directional preference and sensitivity correlated with asymmetric distributions of inhibitory sidebands around BF, as derived from the analysis of OFF-responses.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1494139 TI - Eye movements and brainstem neuronal responses evoked by cerebellar and vestibular stimulation in chicks. AB - The vestibulo-ocular reflex undergoes adaptive changes that require inputs from the cerebellar flocculus onto brainstem vestibular neurons. As a step toward developing an in vitro preparation in chicks for studying the synaptic basis of those changes, we have elucidated the organization of the pathways through which the flocculus influences vestibulo-ocular movements. Electrical stimulation of the vestibular ampulla evoked brief, contralaterally directed movements in both eyes. Although single current pulses to the flocculus elicited no response, conjunctive stimulation of the flocculus and the vestibular apparatus significantly reduced the vestibularly-evoked movement. Trains of current pulses applied to the flocculus and ampulla evoked eye movements directed toward and away from the side of stimulation, respectively. Recordings from the brainstem revealed neurons that were activated by ipsilateral vestibular stimulation and inhibited by ipsilateral floccular stimulation. Our sample included neurons in the lateral vestibular nucleus, the ventrolateral portion of the medial vestibular nucleus, and the superior vestibular nucleus. Similarities between these findings and those of similar studies in mammals indicate that the chick will provide a good model system for cellular studies of adaptive changes in the vestibulo-ocular reflex. PMID- 1494140 TI - Effects of lesion of the inferior olivary complex by 3-acetylpyridine on learning and memory in the rat. AB - DA/HAN-strained male rats (pigmented rats) were submitted to two experimental tasks consisting of spatial learning (water-escape) and a passive avoidance conditioning. Both these tasks were performed by different animals. In order to destroy the inferior olivary complex, the animals were injected with 3 acetylpyridine either 9 days prior to the initial learning session or 24 h after completion of the learning task. They were retested (retrieval test) 10 days after the initial learning was achieved. Learning and retention were compared to those noted in control rats. Administration of 3-acetylpyridine before the initial learning did not prevent the spatial learning but the scores were greatly altered and the number of trials needed to reach the fixed learning criterion was much greater than in controls. However, 10 days later the animals had memorized their initial experience. Injection of 3-acetylpyridine after the initial learning session impaired memory: the animals had completely forgotten their initial learning. It can therefore be concluded that lesion of the afferent climbing fibres to the cerebellar cortex alters learning and retention of a spatial task. Such a lesion does not interfere with learning and retention of a passive avoidance conditioning, since in this condition the experimental animals injected with 3-acetylpyridine either before or after the initial learning behave similarly to controls. The effects of the inferior olivary complex lesion are obviously different according to the task to be learnt, suggesting that these two tasks do not require the integrity of the same nervous structures. PMID- 1494141 TI - Development of brainstem auditory pathway in mallard duck embryos and hatchlings. AB - The development of the brainstem auditory evoked potential (BAEP) was studied in mallard duck (Anas platyrhynchos) embryos and hatchlings from 5-6 days before hatching through two days after hatching in response to tone pips of different frequencies. BAEPs showed a different time of onset and a different rate of development for low, middle, and high frequencies. Although auditory sensitivity in the mid-frequency range (1.0, 1.5, 2.0, and 3.0 kHz) appeared 1-2 days later than in the low-frequency range, development of the BAEPs in the mid-frequency range was almost complete by hatching. In contrast, the development of auditory sensitivity in the low- and high-frequency ranges continued to develop after hatching. Accelerated development of BAEPs to middle frequencies during the embryonic period and to high frequencies after hatching was correlated with the ducklings' exposure to their own mid-frequency and high-frequency vocalizations before and after hatching, respectively. PMID- 1494142 TI - Pilot study results: the psychiatric RN case manager. AB - 1. It is important to examine client and staff satisfaction with the RN case management (RNCM) model to enhance the quality of care in psychiatric settings. 2. Ninety-two percent of clients surveyed ranked the RNCM care as "excellent" or "above average." Clients valued most the humanistic role of the RNCM and repeatedly commented on the importance of the nurse being caring, genuine, and supportive. 3. RNCMs expressed high satisfaction with their role, which they described as collaborative with the psychiatrist, yet also professional and independent. Psychiatrists expressed a high degree of confidence that clients were receiving excellent care by competent nurse professionals. PMID- 1494143 TI - Daily light exposure among psychiatric inpatients. AB - 1. The light environment is a key element in the restoration and maintenance of health. 2. People need exposure to bright light (greater than 2,000 lux) to synchronize their circadian rhythms. 3. The affective state of people is related to their light exposure. 4. Bright light among psychiatric inpatients is low. Interventions to increase light exposure in therapeutic environments and individual care plans are recommended. PMID- 1494144 TI - The use of antidepressants with elderly patients. AB - If we are to prevent treatment failures, we should eliminate the schism between psychosocial and biological treatments. Most depressed patients require both psychosocial and biological treatments. The patient who responds to biological treatment but does not make appropriate corrections regarding current environmental factors is at an increased risk for relapse. A strong support system can have an important preventive effect without the risks involved in long term medication maintenance therapy. After a correct diagnosis of a major depressive disorder is made in elderly patients, the dosage of antidepressants should only be about half of the standard adult dose. Preference should be given to those antidepressants with a therapeutic profile appropriate to each particular patient. The antidepressant should have few side effects. Although antidepressant drugs are effective in treating depression, their demonstrable efficacy is surprisingly limited. Because of suicide risk and physical illnesses, older patients are more likely to require electroconvulsive therapy than younger patients. The presence of somatic delusion is a good predictor of positive response. Newer antidepressants have not been proven more effective than the older agents, such as imipramine or amitriptyline, in treating mild or severe depressions. However, they have fewer or varied side effects and therefore they are better tolerated by elderly patients (Figure 6). The consideration of side effects is a major determinant in choosing an antidepressant for a specific elderly patient. Research into the effectiveness of antidepressants has been limited by the existence of heterogeneous groups of depression and by the different therapeutic responses.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1494145 TI - The mental health of African-American and Caucasian-American women who are homeless. AB - 1. Nurses can use research findings to educate other health professionals about homeless subcultures with attention to specific cultural and socioeconomic needs, as well as to develop interventions for homeless women. 2. Minority women are more susceptible to homelessness as they experience increased poverty levels and are often single mothers. Of all minority women, African-American women are the most vulnerable to physical and psychological illness. 3. In this study, 75% of the subjects had scores on a psychological assessment test that indicated they needed additional psychological testing. PMID- 1494146 TI - Early detection of water intoxication. AB - 1. It has been estimated that between 3% and 6% of patients in psychiatric treatment settings are affected by water intoxication. Water intoxication with consequent hyponatremia can result in disturbing clinical conditions. 2. Early detection is an important factor because of the insidious nature and rapid development of this syndrome. 3. A risk analysis for the early detection of this serious condition has been developed. It is easily administered and effective in categorizing a patient's level of risk. PMID- 1494147 TI - What differences exist between inpatient and outpatient settings for the assessment and intervention for water intoxication? Do interventions differ for special populations, such as the homeless or children? PMID- 1494148 TI - 'Til death do us part: intimacy and sexuality in the marriages of Alzheimer's patients. AB - 1. Alzheimer's disease (AD) is likely to have a significant effect on sexual behavior, but both patient and partner will still have sexual feelings and needs. 2. Research has shown that a high proportion of men with AD develop erection problems, but causes of their erection difficulties are not understood. 3. Research has shown that inappropriate sexual behavior in AD patients is uncommon, although it can be very troubling to the family and health-care provider if it occurs. 4. More professionals need to be trained to discuss sexual issues openly and sensitively with AD patients and partners and to offer useful clinical suggestions. PMID- 1494149 TI - Establishing therapeutic alliance across cultural barriers. AB - 1. The therapeutic alliance is a mutually defined helping relationship that encompasses mutual respect and acceptance of ethnocultural variance, predicated upon empathic rapport. 2. Sensitivity to two psycholinguistic phenomena may help establish a transcultural relationship: the detachment effect (limited expression of affect and reduced access to developmental events between languages) and code switching (a complete or partial change of language or dialect within a single utterance or conversation). 3. Issues related to differing sociocultural expectations of nurses and clients will be increasingly encountered as ease of travel combines with economic and political unrest to produce increasing numbers of displaced persons. PMID- 1494150 TI - Nursing care challenges: homosexual psychiatric patients. AB - 1. Stereotypes of homosexual behavior may negatively affect the nursing care for homosexual patients. Nurses must closely examine their attitudes toward homosexuals. To be able to provide quality care to homosexual patients, nurses must feel comfortable and fully aware of their own attitudes toward sexuality and homosexuality. 2. Nurses stand in a unique position to foster acceptance of homosexuality by assuming the advocacy role and addressing the stereotypes regarding homosexuality for both individual clients and the community. 3. Nurses need to provide an atmosphere of acceptance for homosexual patients by creating an environment where sexuality can be discussed in nonthreatening ways. PMID- 1494151 TI - A target weight procedure for disordered water balance in long-term care facilities. AB - 1. Water intoxication is a severe complication of disordered water balance. Hyponatremia precedes water intoxication and can be identified through abnormal diurnal weight variation. 2. The St. Louis Target Weight Procedure (STWP) is a nonintrusive method that includes a client's baseline weight, frequent weights throughout the day, a target weight of 5% above the baseline weight, and restricted fluids if the target weight is exceeded. 3. The STWP was positively related to an increase in urine concentration; thus it is successful in restoring normal fluid balance. PMID- 1494152 TI - The psychiatric technician: trespasser or welcomed ally? AB - 1. The increasing shortage of nurses, higher patient acuity levels, and greater demands placed on nursing to meet standards of care have contributed to the use of psychiatric technicians to alleviate the burden on nursing and ensure the delivery of quality patient care. 2. Psychiatric technicians provide care for a select group of patients under the supervision of the primary nurse. The patients assigned to psychiatric technicians require minimal direct nursing intervention. 3. Psychiatric technicians reported increased self-confidence and self-esteem; the nurses were able to perform more professional nursing activities, increasing their job satisfaction and promoting staff retention; and the patients received high-quality care. PMID- 1494153 TI - Adherence and accuracy. Self-medication during inpatient psychiatric treatment. AB - 1. The goals of the Medication Education and Self-Administration Program were to develop a way to assess inpatient self-medication accuracy; create a comprehensive intervention that would address individual characteristics that may produce nonadherence; and evaluate the effectiveness of the intervention. 2. The majority of program participants demonstrated significant errors within days when given the opportunity to administer their own medications, suggesting that participants' in-hospital self-administration may be an accurate predictor of postdischarge performance. 3. Even in cases where training failed to influence self-administered performance, program participation provided valuable information that guided subsequent treatment decisions and programmatic refinements. PMID- 1494154 TI - Dysfunctional grieving. AB - Dysfunctional grieving represents a failure to follow the predictable course of normal grieving to resolution (Lindemann, 1944). When the process deviates from the norm, the individual becomes overwhelmed and resorts to maladaptive coping. The process implies movement toward assimilation to or accommodation of the loss, resulting in progression toward social, psychological, and medical morbidity. Nurses will better assess the needs of the client with adequate information about the client's recent losses and perception of those losses. Such an assessment, in conjunction with an understanding of the signs, symptoms, and predisposing factors of complicated bereavement, will enable the nurse to develop a plan of effective intervention. Both case examples illustrate unresolved grief. In Case Example 1, the patient denied the importance of the relationship, which became masked with displaced anger and therefore delayed the grieving process. In Case Example 2, the patient's attempts at grieving over the loss of her son were complicated by her long-standing struggle with her husband's infidelity at the time of her pregnancy. The revelation of secondary loss is common in dysfunctional grieving. Resolution of grief encompasses not only accommodation to object loss, but also change in the pathological behaviors incorporated into the patient's self-image as a result of the loss (Lazare, 1979). The maladaptive operations employed by these patients to preserve self-image were discarded as the grief resolved. The focus of therapy included the loss of those behaviors as they were relinquished to prevent the patient from experiencing further anxiety and sense of loss (Zisook, 1987).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1494155 TI - Language, medicine and diplomacy. PMID- 1494156 TI - Enterostomy feeding for patients with stroke and bulbar palsy. PMID- 1494157 TI - The role of surgery in the management of pulmonary metastasis. PMID- 1494159 TI - Utilization of the Helicopter Emergency Medical Service. PMID- 1494158 TI - Endogenous candida endophthalmitis. PMID- 1494160 TI - An evaluation of the Royal Air Force helicopter search and rescue services in Britain with reference to Royal Air Force Valley 1980-1989. AB - The Royal Air Force (RAF) operates a helicopter Search and Rescue (SAR) service in the United Kingdom and territorial waters; it also provides a similar service in several locations abroad. A 10-year retrospective study of the SAR helicopter service operating from the RAF base at Valley on the island of Anglesey in North Wales is presented, with national SAR statistics over a similar period provided for comparison. Analysis of records kept by SAR aircrew at RAF Valley shows that their assistance had been requested on 1490 occasions during the 10-year period studied; most of these requests were the result of incidents involving holidaymakers, particularly in the mountains or along the coast. The results illustrate the versatility and life-saving potential of a highly skilled and motivated service able to work in adverse weather and dangerous locations. In the light of current debate, the value of aeromedical evacuation of seriously ill patients using helicopters is discussed. PMID- 1494161 TI - Secondary patient transfer by air: an audit of 3 years' experience of the Royal Air Force in the world-wide transport of critically ill patients. PMID- 1494162 TI - Treatment of leg ulcers. AB - A system of treatment of venous leg ulcers by leg elevation, dry gauze dressings and inelastic bandage boots is compared with regimens in which a series of elastic bandage boots are applied to squeeze oedema from swollen ulcerated legs. PMID- 1494163 TI - Public health implications of bovine somatotropin use in dairying: discussion paper. PMID- 1494164 TI - The role of the fifth digit in music: discussion paper. AB - The increasing digital skill made manifest in the development of instrumental music is reviewed and supports the hypothesis that the fifth digit was belatedly used even when a suitable instrument had already become established. With notable exceptions, such as the harp, it appears that progressive improvements in instrument design was influenced by the need to utilize the fifth digits. Its greater use was accomplished in overlapping stages of increasing dexterity, of which the highest is exemplified by the left hand of the violinist. The apparent evolutional background of these observations is discussed. It is proposed that man has an inherent atavistic tendency to ignore the fifth digit and this view agrees with its neglect in gesture and sign language. PMID- 1494165 TI - Allergic bronchopulmonary aspergillosis: a review. PMID- 1494166 TI - Pancytopenia related to azathioprine--an enzyme deficiency caused by a common genetic polymorphism: a review. PMID- 1494167 TI - A case of appendico-vesical fistula. PMID- 1494168 TI - Recurrent neck abscess caused by a fourth pharyngeal pouch sinus. PMID- 1494169 TI - Surgical voice restoration after laryngopharyngectomy with free radial forearm flap repair using a Blom-Singer prosthesis. PMID- 1494170 TI - Action myoclonus after cerebral hypoxia: treatment with clonazepam. PMID- 1494171 TI - Continuous catheter drainage of Streptococcus pneumoniae pericardial effusion. PMID- 1494172 TI - Progressive chronic pulmonary aspergillosis: a diagnostic and therapeutic challenge. PMID- 1494173 TI - Medico-legal value of postmortem assay of potassium concentration in vitreous humour. PMID- 1494174 TI - Parietal abdominal pain. PMID- 1494175 TI - General practitioners' use of non-steroidal anti-inflammatory drugs in Tayside and Fife regions. PMID- 1494176 TI - Mitral valve prolapse, keratoconus and Down's syndrome. PMID- 1494177 TI - Age changes in teeth. PMID- 1494178 TI - Real-life performance considerations of four pediatric multi-channel cochlear implant recipients. AB - Most pediatric cochlear implant programs support a team approach for post-implant services. However, individuals directly involved in the care of these children often have differing opinions on the child's performance. We describe our experience with four children, aged 3 to 10 at the time of implantation, who have used the Nucleus 22-channel cochlear implant device for at least nine months. A questionnaire, focusing on the individual's observations of the child's speech and hearing performance in their particular setting (i.e., clinic, home, school), was completed by the child's parent(s), therapist and classroom teacher. Overall, performance in structured settings (i.e., testing and therapy sessions) was not in agreement with performance in unstructured settings (i.e., classroom and home environments). The results suggest that different individuals interacting with the same child in different environments often have differing perceptions of the child's performance. Based on the information obtained on the four cases, we discuss factors to consider in assessing the real-life performance of pediatric cochlear implant recipients. PMID- 1494179 TI - Down syndrome: an otolaryngologic perspective. AB - The otolaryngologic manifestations of Down syndrome often masquerade as common and seemingly trivial conditions. Behind this facade lies a broad spectrum of disease which can detract from an inherently diminished level of function and jeopardize survival. This paper examines the pertinent associations between Down syndrome and various pathological entities related to the head and neck. Evaluation of current therapeutic modalities reinforces the need for early diagnosis and treatment so that the potential of this patient group is fulfilled. PMID- 1494180 TI - Practical aspects of managing non-malignant lumps of the neck. AB - The etiologies of pediatric neck masses are legion. Optimal management depends upon making the correct diagnosis. A detailed history to ascertain the duration of the illness, presence of systemic symptoms, animal exposures, tuberculous contacts, medications ingested, recent trauma, dental work or upper respiratory infection (URI), as well as a travel history, may yield important clues to establishing the diagnosis. The work-up for neck masses must be individualized based upon history and physical examination. Common diagnostic studies often obtained are listed in Table 1, and will be further clarified as individual diagnoses are discussed. PMID- 1494181 TI - Failed tracheotomy decannulation in children. AB - Airway lesions preventing tracheotomy decannulation may not always be readily apparent or may be underestimated by the inexperienced observer. Examples of tracheal keloid, tracheomalacia due to vascular compression, vocal cord dislocation and fixation and subglottic webbing with emphasis on the need for meticulous endoscopy are demonstrated. PMID- 1494182 TI - Practical aspects of pediatric tracheotomy care. AB - Infants and children who manifest respiratory distress secondary to congenital or acquired abnormalities of the airway pose a unique problem that frequently requires a tracheotomy to control the patient's airway. These tracheotomies often are required for extended periods of time. Skilled care and astute observation are essential for the care of these patients while in hospital and at home. Although many of the care concerns relate to nursing and social issues, the otolaryngologist must maintain an active role in the medical management and co ordination of discharge. This paper provides the otolaryngologist with an outline of the hospital care required for the pediatric tracheotomy patient. Additionally, it offers the otolaryngologist a model program for discharge planning and follow-up for the pediatric tracheotomy patient in the community. PMID- 1494183 TI - Evaluation and management of the drooling patient. AB - Drooling, or sialorrhea, may appear to be a most mundane problem but in fact can be a condition with a wide spectrum of etiologies. Unhappily, drooling also may lead to several unfortunate medical and psychosocial outcomes for the affected patient. The senior author (WSC) has had a 13 year interest in the treatment of drooling patients. This paper is essentially a distillation of the experience gained in managing these patients. Since 1979 he has participated in a team (which includes an otolaryngologist, a dentist and a speech pathologist) that attends these patients and makes recommendations in a consensus fashion. This team concept, as well as historical and physiologic background material, will be discussed below. PMID- 1494184 TI - Subglottic hemangioma: a practical approach. AB - A specific entity known as a subglottic hemangioma may present in a six to 12 week-old baby with gradual onset of a two-way stridor. A cough may be present. The voice and feeding may be normal, until severe airway obstruction occurs. A barium swallow with fluoroscopy should be performed by a radiologist or technician experienced with babies to rule out other lesions such as a vascular ring. Direct examination is then performed using a 3.0 mm Storz-Hopkins bronchoscope under general anesthetic as a method of choice. Other methods are discussed. Ideal treatment is probably best undertaken in a large center, using a carbon dioxide laser through a subglottiscope again under general anesthesia with the child breathing spontaneously. Airway support may be necessary at any stage. Alternative treatments are discussed. PMID- 1494185 TI - Salivary gland disease in infancy and childhood: non-malignant lesions. AB - The differential diagnosis for benign lesions of the salivary glands in infancy and childhood can be somewhat overwhelming, especially in light of their infrequent occurrence in a general otolaryngologic practice. The purpose of this review is to discuss these conditions under the headings of inflammatory conditions, immunologic disorders, granulomatous disease, trauma, cysts, systemic disorders and benign neoplasms. Basic techniques of diagnosis and treatment as they apply to children will be outlined. PMID- 1494186 TI - Practical aspects of managing the child with apnea. AB - Sleep apnea is a common problem in children and probably more common than currently realized. Apnea in children may be central, obstructive or mixed. Otolaryngologists are called upon to diagnose and treat obstructive apnea. The most common cause of obstructive apnea in children is adenotonsillar hyperplasia, and several conditions predispose children to sleep apnea. The most severe, and occasionally only, signs occur during sleep. The majority of children can be diagnosed by a careful history from parents or caretakers. However, sleep sonography, pulse oximetry and polysomnography may be needed to assist in diagnosis. The treatment of apnea in children may include medications, but the most common procedure employed to resolve obstructive apnea in children is adenotonsillectomy. PMID- 1494187 TI - Differential bacteriology in adenoid disease. AB - In order to define the differential bacteriology in adenoid disease, adenoids were obtained from 10 children with adenoid hypertrophy and 29 children with chronic adenoiditis. The patients' ages ranged from 18 months to 13 years. After removal of the adenoids, the surface organisms were destroyed by alcohol and flame disinfection. One gram of tissue was sampled for aerobic and anaerobic culture. There was an average of 4.8 isolates per specimen, with 4.2 aerobes and 0.6 anaerobes. The most common isolates were: Haemophilus influenzae (84%), diphtheroids (66%), non-pathogenic Neisseria species (66%), alpha-hemolytic streptococci (64%) and non-hemolytic streptococci (59%). Anaerobes were present in 56% of all cases. The distribution of organisms was similar, regardless of clinical diagnosis. Only eight (21%) of the 39 cases had 'significant' (> or = 10(5) organisms/gm) colony counts. Our study detected no difference in either organism distribution or in total colony counts in chronic adenoiditis vs. adenoid hypertrophy. PMID- 1494188 TI - Paroxysmal sneezing in children: two new cases. AB - Paroxysmal sneezing is an uncommon condition primarily affecting adolescents. Most of the reported cases were thought to be psychogenic, and only two were felt to be due to nasal sensitivity. This paper reports two adolescents with paroxysmal sneezing, neither of whom had apparent psychologic or emotional problems. In one child the sneezing continued during sleep. The other child was successfully treated with topical nasal anesthesia. Both children were felt to have nasal sensitivity as the etiology of their paroxysmal sneezing. The evaluation of the patient with paroxysmal sneezing requires a thorough history and physical examination. One must not assume that every case of paroxysmal sneezing is of psychogenic origin. Topical nasal anesthesia should be tried for control of intractable paroxysmal sneezing. PMID- 1494189 TI - The effect of peritonsillar infiltration on intra-operative blood loss in children. AB - Infiltration of the peritonsillar space in one group of patients with lidocaine 0.5% containing epinephrine (Group I) and with normal saline in another (Group II) did reduce the intra-operative blood loss significantly compared to the control group (Group III) who did not get any injections. The benefits of reducing intra-operative blood loss in children is discussed. PMID- 1494190 TI - Fibrosarcoma of the infratemporal fossa in childhood: a challenging problem. AB - Fibrosarcoma in childhood is a rare disease. An interesting new case involving the infratemporal fossa in a three-year-old girl is reported. The literature, the symptomatology and the diagnostic features are reviewed. The difficult management decisions and the thorny problem of reconstruction of head and neck malignancies in growing children are discussed. Suggestions are made for management of similar cases. PMID- 1494191 TI - Fourth branchial cleft cyst. AB - Remnants of the fourth branchial arch are uncommon clinical entities. They may present in either the neck or chest in association with aortic arch development. They are encountered more frequently in younger individuals as an asymptomatic left-sided neck mass, recurrent neck abscess or suppurative thyroiditis. In view of the rarity of this lesion, we thought it worthwhile to present the case of a 25-year-old female with a diagnosed fourth branchial cleft cyst in her left lower neck. The embryology and management of these cases is discussed. PMID- 1494192 TI - Pediatric laryngeal granular cell tumor. AB - Granular cell tumor of the larynx is an uncommon, benign tumor which has rarely been described in the pediatric population. Fewer than 10 cases in children under the age of 10 years have been reported. This paper describes two pediatric patients: An eight-year-old boy with a seven-year history of hoarseness due to an anterior subglottic tumor, and an 11-year-old boy with a one-year history of hoarseness due to a left true vocal cord tumor. Subglottic involvement by laryngeal granular cell tumor is rare in adults, but has been seen in half of the reported cases in the pediatric population. The clinical course of granular cell tumor and its pathology are reviewed. PMID- 1494193 TI - Bone scanning in masked mastoiditis. PMID- 1494194 TI - The hazards of button batteries in the nose. AB - Foreign bodies in the nose are commonly encountered in ORL practice. Miniature button battery impaction in the nose has rarely been reported. Seven such cases have been encountered, each suffering complications directly attributable to the button battery. The complications included septal burns in five patients leading to septal perforation in one child, one case of severe nasal bleeding and one case of necrosis of the lateral nasal wall. The site of maximal damage corresponded with the negative pole of the battery in every case. The possible explanation for this and mechanisms of cellular injury are proposed. This paper underlines the potential hazards of button batteries as foreign bodies in the nose and emphasizes the need for rapid removal and long-term follow-up of these patients. PMID- 1494195 TI - New scoring system for prediction of ovarian malignancy based on transvaginal color Doppler sonography. AB - The goal of this prospective study was to develop a new scoring system using transvaginal color and pulsed Doppler characterization of ovarian lesions. Transvaginal color Doppler sonography was performed on 812 women, among whom 174 adnexal masses were found and analyzed. Ovarian lesions were assessed by means of morphological and color Doppler scoring systems. Tumors were characterized ultrasonically as benign or suspected of being malignant. Scoring system results were correlated with histopathological findings. Among our study group, 38 malignant and 136 benign ovarian tumors were found and verified. The color Doppler scoring system was very useful in distinguishing benign from malignant masses, with a sensitivity of 97.3% and a specificity of 100%, compared with the morphological scoring system's sensitivity of 92.1% and specificity of 94.8%. We also evaluated a combination of both scoring systems. We believe that new color Doppler scoring system maximizes the ability to discriminate between benign and malignant entities. PMID- 1494196 TI - Intrarenal Doppler: characteristics of aging kidneys. AB - The normal range of Doppler findings in native kidneys has not been studied extensively. This study correlates changes in Doppler resistive index (RI) with age in patients without renal risk factors or renal disease. Young and old patients demonstrated the highest RI values (age < 1, mean RI = 0.73; age > 59, RI = 0.68), and patients in the 20-39 year age group showed the lowest values (RI = 0.59). The mean RI for all ages was 0.63. The cause of this variability is unknown. We suggest that age-related changes in Doppler values should be considered in the interpretation of renal Doppler measurements. PMID- 1494197 TI - Spontaneous improvement of intrathoracic masses diagnosed in utero. AB - The diagnosis and pregnancy outcome for 14 fetuses with sonographically detected chest masses were reviewed retrospectively. Six lesions became smaller or less apparent during gestation or resolved between antenatal and perinatal imaging studies; these included all three types of cystic adenomatoid malformation (CAM), as well as one case of pulmonary sequestration (PS). This information is extremely important in counseling patients in the second trimester who are considering termination of pregnancy. The poor prognosis traditionally assigned to type II and type III CAM needs changing to reflect the phenomenon of improvement with excellent long-term outcomes. Sonographic indicators of poor outcome were polyhydramnios, hydrops or marked cardiac deviation. PMID- 1494198 TI - Fetal stomach measurements: not reproducible by the same observer. AB - We hypothesized that because fetal stomach filling and emptying is a dynamic process, measurements of the stomach dimensions might not be reproducible. Serial measurements 20 minutes apart were made of the stomach in 146 fetuses at 14 to 41 weeks of gestation. In 88 of these fetuses, the biparietal diameter also was measured to provide a standard for comparison. The mean percentage change between each of the paired measurements was 16.6% to 43.1% for the different stomach dimensions, compared with only 2% for the biparietal diameter (P < 0.001). We suggest that caution be excised in the diagnostic use of stomach measurements owing to their dynamically changing nature. PMID- 1494199 TI - Sonographic approach to diagnosing pulmonary consolidation. AB - Thirty-nine consecutive patients with consolidated lung confirmed radiologically underwent sonography, and their sonograms were compared with results for 100 healthy subjects. The hyperechoic line of normal aerated lung and its air artifacts showed respiratory motions ("gliding sign," n = 100). Patients with pneumonia demonstrated distinct sonographic patterns. Strong linear echoes with characteristic air artifacts (air bronchogram) and anechoic tubular structures (fluid bronchogram) were visualized in 36 of 39 patients (92.30%). The superficial lung showed a homogeneous hypoechoic band termed "superficial fluid alveolograms" (n = 39) with respiratory motions in 35 of 39 patients. We conclude that sonography can evaluate pulmonary consolidation and may provide additional roentgenographic information, especially when fluid bronchograms are visualized. PMID- 1494200 TI - Ultrasonographic prenatal diagnosis of upper respiratory tract atresia. PMID- 1494201 TI - Echogenic colonic meconium in the third trimester: a normal sonographic finding. PMID- 1494202 TI - Aspiration of bilateral perinephric urinomas and vesicoamniotic shunt placement in fetal bladder outlet obstruction. PMID- 1494203 TI - Meconium thorax: prenatal sonographic diagnosis. PMID- 1494204 TI - Improved growth and disease activity after intermittent administration of a defined formula diet in children with Crohn's disease. AB - Growth failure is the most common extraintestinal manifestation of Crohn's disease in childhood, occurring in up to 50% to 88% of affected patients. Previous studies have shown malnutrition to be the most likely cause of the decrease in height and weight velocities in these children. The purpose of this study was to determine the effect of an intermittent defined formula diet on growth and disease activity in children with Crohn's disease and growth failure. Six Tanner stage I-II patients, mean age 13.6 years with height less than the 5th percentile or height velocity less than the 3rd percentile were enrolled in a 1 year prospective study. An isotonic, hydrolyzed whey, medium-chain triglyceride formula was given by nocturnal nasogastric infusion at a caloric equivalent of 50th percentile for age, as the exclusive nutrient source 1 out of 4 months during a 1-year period. A 2-week exclusion diet and a 2-week low-residue diet followed the defined formula diet before resuming the regular diet for 2 months. Patients served as their individual control based on observations of at least 1 year before the study. Height and weight velocity significantly increased. Prednisone intake significantly decreased, and significant improvement was seen in disease activity, albumin, and somatomedin C. The results indicate that an intermittent defined formula diet can improve growth failure and significantly decrease disease activity in children with Crohn's disease. PMID- 1494205 TI - Ornithine alpha-ketoglutarate and glutamine supplementation during refeeding of food-deprived rats. AB - The aim of this study was to compare the efficiency of ornithine alpha ketoglutarate (OKG) and glutamine supplementation in an experimental model of denutrition that provides well-characterized disturbances of amino acid patterns. Male Wistar rats (187 +/- 11 g; five in each group) were starved for 3 days and then refed for 7 days with an oral diet (192 kcal kg-1.day-1 and 2.25 g of nitrogen kg-1.day-1), supplemented with 0.19 g of nitrogen kg-1.day-1 in the form of OKG, glutamine, or casein (control group). Food deprivation induced a fall in most tissue amino acids, with the notable exception of muscle leucine and liver glutamate, which increased by 43% (p < .01), and 11% (p < .05), respectively. The main effect of OKG was seen in the viscera, with a normalization of most amino acid pools (including proline and branched-chain amino acids) in the small bowel and liver. The main effect of glutamine was observed in the muscle, with a normalization of the glutamine and leucine pools. We conclude that, in this model and with the doses used, OKG and glutamine act in different target tissues, ie, splanchnic areas and muscle, respectively. PMID- 1494206 TI - Substrate efficacy in early nutrition support of critically ill multiple trauma victims. AB - The metabolic consequences of excessive nutrition support in patients have been increasingly recognized in recent years. Time-dependent optimal nutrition support is desired for an early and uncomplicated recovery after severe injury or illness. Metabolic effects of adding balanced amino acids to glucose infusion during total parenteral nutrition were investigated in 18 patients after major trauma (injury severity score 32 +/- 2). Two studies were conducted on each subject, one in the early "flow" phase of injury (40-60 hours postinjury) in the basal state without any dietary intake and then after 4 to 6 days of intravenous nutrition provided solely as glucose (24 +/- 2 kcal/kg per day, 80% resting energy expenditure, n = 8) or isocaloric glucose (28 +/- 3 kcal/kg per day) with amino acids (275 +/- 28 mg of nitrogen per kilogram per day, n = 10). Whole-body fuel substrate kinetics were studied for energy metabolism (indirect calorimetry), protein kinetics (primed-constant infusion of 15N glycine), and lipid mobilization (two-stage infusion of 10% glycerol). Injury-induced hypoaminoacidemia was equally modulated whether the glucose-based nutrition had amino acids or not. The negative nitrogen balance is reduced similarly in both groups. Protein breakdown rate is significantly (p = .025) decreased in both groups and it is more so (30% vs 18%) in patients receiving total parenteral nutrition. Intravenous nutrition could not stimulate protein synthesis. Whole body lipolysis rate as well as net fat oxidation rate are suppressed more when glucose alone is given, and this also results in less reesterification. Provision of intravenous glucose alone, not to exceed the resting energy expenditure, seems to be superior to isocaloric glucose with amino acids during this early catabolic flow phase of injury because the injured body could not assimilate this exogenous amino acid. PMID- 1494207 TI - Effect of excess xylitol on nitrogen and glucose metabolism in parenterally fed rats. AB - The objectives of this study were to investigate the effects of an excess of xylitol on nitrogen balance and glucose metabolism in parenterally fed rats. Female Sprague-Dawley rats (200-250 g, n = 17) were catheterized for total parenteral nutrition and then randomized into two groups based on subsequent diet. The two diets used were isonitrogenous (1.5 g of nitrogen per kilogram per day) and isocaloric, with half the calories (125 kcal/kg per day) being derived from lipid (125 kcal/kg per day) and the other half from either glucose or xylitol (125 kcal/kg per day). The rats were fed a half-strength total parenteral nutrition diet for the day after surgery and a full-strength total parenteral nutrition diet for the following 4 days. Urines were collected daily for the determination of nitrogen balance. On day 5, the rats were given a 7- to 8-hour infusion of 6.6-d2 glucose (6 mg/h and 2-d1 glucose (12 mg/h). At the conclusion of the isotope infusion period, the rats were killed and blood was collected. Urine output was increased by 22% per day in the xylitol-treated rats, and they excreted 46.5 mmol of xylitol per liter per kilogram per day (7.1 g/kg per day, approximately 22.7% of dose). The xylitol group lost weight, had poorer nitrogen balance (341 +/- 31 vs 83 +/- 29 mg/kg per day [mean +/- standard error of the mean], p < .05), and developed fatty livers. Analysis of the liver fat distribution pattern indicated that the source of the excess hepatic lipid was dietary fat.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1494208 TI - Continuous compared with intermittent tube feeding in the elderly. AB - The methods of continuous (C) and intermittent (I) nasogastric tube feedings in 60 patients, 54 men and 6 women, with a mean age of 72 +/- 9 years were compared in terms of number of complications, staff time used, and caloric intake. Patients were randomly assigned between these two methods and followed for 7 days. Diarrhea, aspiration pneumonia, clogged tubes, and self-extubation were observed in both groups. Diarrhea was significantly more frequent (96% of 30 patients) in the I group than the C group (66% of 30 patients) (p < .008). Furthermore, diarrhea was more prolonged (4 days or more) in 64% of 30 patients in the I group than the C group (4 days or more) in 58% of 30 patients (p < .02). However, clogged tubes occurred 3 times more often in the C group (p < .01). Self extubation and aspiration pneumonia tend to be more frequent in the I group but the difference was not significant. The average time used by staff nurses in the maintenance of NGT feedings was not significantly longer in the I group (48.45 +/ 11 min/patient per day) than the C group (46.46 +/- 11 min/patient per day). In the C group the mean calories recommended were 2248 +/- 36 kcal/day but the actual caloric intake was only 1465 +/- 281 kcal/day, a deficiency of 783 +/- 291 kcal/day. The recommended calorie count for the I group was 2021 +/- 5 kcal/day but the amount delivered was only 1226 +/- 254 kcal/day, which resulted in a deficit of 795 +/- 259 kcal/day.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1494209 TI - Polymyxin B reduces total parenteral nutrition-associated hepatic steatosis by its antibacterial activity and by blocking deleterious effects of lipopolysaccharide. AB - Overgrowth of Gram-negative bacteria as a result of total parenteral nutrition (TPN) and bowel rest could be responsible for the release of a variety of hepatotoxic substances such as endotoxin or tumor necrosis factor (TNF) and the ensuing TPN-associated liver function derangements. Polymyxin B is an effective antimicrobial agent as well as a blocking agent for endotoxin (lipopolysaccharide) activity and TNF production. In the present study we compared the oral and intravenous effects of polymyxin in rats receiving TPN in an attempt to define these two possible mechanisms of action of polymyxin on TPN associated hepatic steatosis. Both oral, as well as intravenous polymyxin B, significantly reduced total hepatic fat and triglyceride accumulation in TPN rats, more so in the intravenous group exhibiting close to control levels. Both polymyxin-treated groups exhibited significantly lower Gram-negative bacterial counts in the cecum, with the oral group exhibiting a lower count than the IV group. The spontaneous production of TNF by peritoneal macrophages was markedly increased in rats receiving TPN and very close to being undetected in both groups receiving TPN and polymyxin. We believe polymyxin B protects the liver during TPN by both its antimicrobial effect which prevents overgrowth of gut Gram-negative bacteria and the subsequent translocation of endotoxin, and by its specific antilipopolysaccharide activity which, in the present study, completely abolished hepatic steatosis and TNF production during TPN. PMID- 1494210 TI - Effect of a single oat bran cereal breakfast on serum cholesterol, lipoproteins, and apolipoproteins in patients with hyperlipoproteinemia type IIa. AB - Serum cholesterol-lowering effects of oat bran-enriched diets have been indicated in several studies in which oat bran was given several times a day. Concomitant changes in the daily diet, ie, a diminished energy intake or changes in the composition of fats in the diet, also have been reported and used to explain the hypocholesterolemic effect of oats. The present study was designed to replace only the conventional continental breakfast by a single oat bran cereal muesli containing 60 g of oat bran and to measure the effects of this dietetic modification on serum lipids in 13 patients with hypercholesterolemia type IIa. Compared with a 3-week baseline period, total serum cholesterol (7.38 +/- 0.35 mmol/L, mean +/- SEM) was reduced by 10.9, 8.4, and 9.7% in the first, second, and third week of oat bran ingestion (p < .01). High-density lipoprotein and low density lipoprotein cholesterol as well as apolipoprotein A1 decreased to the same extent (8 to 11%; p < .05) during the oat bran period, whereas a pronounced reduction of 25.8% was seen for apolipoprotein B100 (p < .01), which is a major component of low-density lipoprotein. Dietary data obtained by 3-day food records at baseline, oat bran, and follow-up period did not show any differences between the study periods except for dietary fiber, which was increased from 21.9 g/day to 42.4 g/day (p < .002) during the test period because of the daily oat bran intake.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1494211 TI - Effects of different lipid sources in total parenteral nutrition on whole body protein kinetics and tumor growth. AB - This study examined the short-term effects of three total parenteral nutrition solutions, each containing a different lipid source, on host and tumor protein metabolism in a rat cancer model. Each diet contained 220 kcal/kg per day, including 2 g of nitrogen/kg per day and 50% of nonprotein calories as either a structured lipid of medium-chain triglycerides and fish oil, a physical mix of medium-chain triglycerides and fish oil, or Liposyn II, a long-chain triglyceride. A 3-day intravenous feeding infusion began on day 7 after tumor implantation. Tumor growth rate, nitrogen balance, energy expenditure, and plasma albumin, glucose, and free fatty acids were measured, and whole body protein kinetics and fractional synthetic rates in liver, muscle, and tumor tissues were assessed using a constant infusion of 14C-leucine. The results revealed that tumor growth rate was slowed in structured lipid-fed animals (p = .06, one-way analysis of variance) with significant increases in rates of tumor protein synthesis and tumor protein breakdown (p < .001, one-way analysis of variance). Although muscle fractional synthetic rates were significantly decreased in tumor bearing animals (p < .05, two-way analysis of variance), the rates in structured lipid-fed animals were restored. Nitrogen balance improved significantly in structured lipid-fed animals. The results demonstrate that the source of lipid in total parenteral nutrition solutions can influence tumor and host protein metabolism, and that a structured lipid composed of medium-chain triglycerides and fish oil seems to improve protein metabolism in host tissue without stimulating tumor growth. PMID- 1494212 TI - Microbial contamination of enteral feeding tubes occurring during nutritional treatment. AB - Enteral nutrition is an effective treatment for catabolic patients with normal intestinal absorption. However, tube-fed patients are at risk from superinfection. Our study is the first to evaluate in vivo the microbial contamination of solutions staying in the nasogastric tube of cancer patients receiving nutritional preparations. After daily feeding, the tube was rinsed with nonsterile tap water. Tap water staying overnight in the tube was considered as tube-rinsing solution. Microbial burden of nutritional preparations was determined on the fifth day of enteral nutrition, from opening the first container and throughout feeding. The next day, a sample of the tube-rinsing solution was cultured. All bacterial species were identified and antibiotic susceptibility pattern was assessed. Thirty-one cancer patients were included, 12 on the hospital's preparations and 19 on commercial feeding. Seven of the hospital--and none of the commercial--preparations were contaminated. Among the 48 samples collected during feeding, 16 were contaminated, including 10 hospital and 6 commercial preparations. All the 31 tube-rinsing solutions were contaminated and 102 strains cultured. Their median concentration was 10(6) colony-forming units/mL (range 10-10(10)). The strains were 48 Enterobacteriaceae, 20 group D streptococci, 9 Candida albicans, 9 Pseudomonas aeruginosa, and 16 others. Multiple antibiotic resistance was present in 12 of the 102 strains. Lower resistance was present in 33. The predominant microorganism of the tube-rinsing solution caused a bacterial colonization for three febrile patients. In conclusion, the feeding tube is an important reservoir for multiple antibiotic-resistant bacteria. PMID- 1494213 TI - Acute phosphate intoxication in seven infants under parenteral nutrition. AB - After major surgery, seven infants aged 4 to 29 weeks, under parenteral nutrition, received monosodium phosphate (4.2 to 14.3 mEq/kg body weight) instead of prescribed calcium gluconate. The wrong solution was perfused during 16 hours. At the 15th hour, blood samples showed hyperphosphatemia in all (8.0 to 14.4 mg/100 mL) and hypocalcemia in four infants (6.1 to 8.0 mg/100 mL), but all were asymptomatic. Under a perfusion of glucose in water, calcemia and phosphatemia returned to normal within 24 hours. In a review of the pediatric literature, we found 11 subjects with symptomatic acute phosphate intoxication, who also presented with hypocalcemia and hyperphosphatemia. The differences were that they received high bolus doses of phosphate orally or rectally and showed symptomatic features. Normalization of the calcemia occurred only when hyperphosphatemia was corrected throughout intravenous hydration. PMID- 1494214 TI - The role of protein and calorie restriction in outcome from Salmonella infection in mice. AB - We studied the separate effects of protein and calorie restriction in mice challenged with Salmonella typhimurium, an intracellular pathogen eliminated by cell-mediated immunity. Female A/J mice (n = 73) were placed on one of eight solid diets for 3 weeks. Animals were weighed at the beginning and the end of the feeding period. Diets were adjusted by two factors. The total amount of protein in the diet was 1%, 5%, 20%, or 40% by weight. The diets were fed to half the mice in quantities of 3 g and to the other half at 1.5 g per mouse per day. At the end of 3 weeks, mice were injected intraperitoneally with bacteria and mortality was observed for 2 weeks. Mortality was related to protein intake and was significantly higher in the 1% and 5% groups (chi 2: p = .0021). However, mortality was lower in the calorie-restricted groups (chi 2: p = .0242). Although caloric intake did not affect cell-mediated immunity, the response to 2,4 dinitrofluorobenzene was greater in the low protein groups. Lymphoproliferative responses in the mixed lymphocyte response were not affected by either caloric or protein intake. Lymphoproliferative responses to both lipopolysaccharide and phytohemagglutinin were affected by dietary protein but not by caloric intake; proliferative responses were higher in the low-protein groups. We conclude that protein restriction can increase mortality in this model. On the other hand, short-term calorie restriction can improve survival. PMID- 1494215 TI - Variability of the Harris-Benedict equation in recently published textbooks. AB - The Harris-Benedict equation, as cited in a selection of textbooks of medicine, surgery, and nutrition, was compared with the original monograph published by the Carnegie Foundation. A significant amount of variation was found in published versions of this equation. Of 24 published versions, eight were sufficiently variant to produce errors of 7% to 55% in calculations of nutrition requirements. The error is usually in the constant term for one of the two Harris-Benedict equations. Either the constant term for men is increased to a value approximately the same as for women, or the constant term for women is reduced to be approximately equal to that for men. The primary reason appears to be the lack of availability in medical libraries of the original Carnegie Foundation publication by Harris and Benedict. PMID- 1494217 TI - Placement of a duodenal feeding tube via gastrostoma with fiberoptic bronchoscope. AB - We report a case of esophageal disruption that required a duodenal feeding tube. Because of collapse of the gastric outlet secondary to severe emaciation, several attempts to place a tube into the duodenum via gastrostoma had ended in failure. We finally were able to accomplish it with the aid of a fiberoptic bronchoscope and a Swan-Ganz catheter. The procedure is described and discussed. PMID- 1494216 TI - How amino acids get into cells: mechanisms, models, menus, and mediators. AB - The bloodstream provides a readily available pool of amino acids, which can be taken up by all cells of the body to support the myriad of biochemical reactions that are essential for life. The transport of amino acids into the cytoplasm occurs via functionally and biochemically distinct amino acid transport systems that have been defined on the basis of their amino acid selectivities and physico chemical properties. Each system presumably relates to a discrete putative membrane-bound transporter protein that resides within the cell membrane and functions to translocate the amino acid from the extracellular environment into the cytoplasm. Many of these transporters require sodium for maximal activity. The sodium-dependent model presented is consistent with "preferred random" kinetics, with sodium binding preferentially before the amino acid. The transporter acts as an enzyme that catalyzes the movement of its bound amino acid (and sodium) into the cell. In this review, the authors provide a conceptual view of the mechanism of carrier-mediated amino acid transport as well as an overview of the various models that can be used in the laboratory to study this process. In addition, the known agencies that accomplish transport and their regulation by nutrition, hormones, and other mediators of critical illness are discussed. PMID- 1494218 TI - Prevention of catheter-related sepsis during parenteral nutrition: effect of a new connection device. AB - A prospective study was carried out to determine the clinical effect of a newly devised catheter connection method (I system) and piggyback access system. Previous studies have demonstrated that the I system avoided bacterial contamination in vitro during tubing change that Luer-Lock connectors did not. The purpose of this study was to investigate the ability of this device coupled with a new closed-system piggyback technique for multipurpose access to reduce catheter-related sepsis in clinical practice. Two hundred and thirty patients receiving total parenteral nutrition were divided into two groups. Group I (n = 106) used the I system connector and group L (n = 124) used a Luer-Lock connector. Catheters in both groups were used for multipurpose access for infusion and blood sampling. In group L, a three-way stopcock and/or pig-gyback system was used for multiple access. In group I, a newly designed closed-system piggyback was used. The incidence of catheter-related sepsis was significantly lower in group I (1.89%/catheter) than in group L (12.10%/catheter) (p < .01, chi 2 analysis), and the average duration of use of each catheter was significantly longer in group I than in Group L (p < .01 by generalized Wilcoxon test). The results of this clinical study suggest that the newly designed connection method and piggyback access system are able to reduce catheter-related sepsis. PMID- 1494219 TI - The effect of tumor bulk on the metabolic response to cancer. PMID- 1494220 TI - Clinical comparison of tolerance to elemental or polymeric enteral feedings in the postoperative patient. PMID- 1494221 TI - Clinical and metabolic efficacy of glutamine-supplemented parenteral nutrition after bone marrow transplantation. A randomized, double-blind, controlled study. PMID- 1494222 TI - Fat elimination in acute renal failure: long-chain vs medium-chain triglycerides. PMID- 1494223 TI - Evaluation of the predictive performance of nutritional indicators by ROC curve analysis. PMID- 1494224 TI - Estimating energy expenditure. PMID- 1494225 TI - More on risk factors for central venous catheter-related vascular erosions. PMID- 1494226 TI - Urokinase infusion for thrombosed catheters. PMID- 1494227 TI - [Antimicrobial activities of ceftazidime on fresh clinical isolates]. AB - Antimicrobial activity of ceftazidime (CAZ) was compared with those of other cephem antibiotics against clinically isolated strains sent to us by medical institutions throughout Japan in 1989 and 1991. Those strains separated and identified from samples collected from patients with various infections were also examined, and the following results were obtained. 1. The results suggested that, compared with reports of studies conducted with clinical isolates in early 1980's, MIC90 of CAZ in 1991 were markedly higher against Staphylococcus spp., Streptococcus pneumoniae, Escherichia coli, Enterobacter spp., Serratia marcescens, Proteus vulgaris, Morganella morganii, and Pseudomonas aeruginosa. Also, among other bacteria such as Providencia rettgeri, Providencia stuartii, Xanthomonas maltophilia, and Bacteroides fragilis group, strains resistant to CAZ were observed in high proportions. However, large time-course changes were not observed in microbial activities of CAZ on Streptococcus pyogenes, Klebsiella spp, Proteus mirabilis, Pseudomonas cepacia, Acinetobacter calcoaceticus, Haemophilus influenzae and Anaerobic GPC (Gram-positive cocci). 2. Among the strains used in the study, methicillin-resistant Staphylococcus aureus (MRSA), Benzylpenicillin (PCG)-insensitive S. pneumoniae (PISP), cephamycin and oxime type cephem-resistant Gram-negative bacilli of Enterobacteriaceae and new quinolone-resistant organisms were observed in high proportions. It appears therefore, that CAZ failed to exert sufficient antimicrobial activities to these strains because of combination of resistance in these strains. 3. Antimicrobial activities of CAZ on recent clinical isolates showed problems as mentioned above. However, it was also demonstrated that CAZ maintained effective antimicrobial activities against most of the clinical isolates which could be causative organisms of infectious diseases in the clinical practice. When it is additionally taken into account that CAZ is one of those limited drugs with activity against P. aeruginosa, and it has excellent permeability through outer membrane, it is concluded that CAZ still is one of the clinically useful cephem drugs in 1990's. PMID- 1494228 TI - [Antimicrobial activity of cefetamet against clinically isolated microbial strains collected from urban RTI patients]. AB - The authors studied antimicrobial activities of cefetamet (CFMT) and other leading oral antimicrobials of beta-lactam class against clinically isolated strains from urban respiratory tract infection (RTI) patients from January to March, 1992. 1. CFMT showed potent antimicrobial activities against "3 primary pathogens" of RTIs i.e., Streptococcus pyogenes, Streptococcus pneumoniae, and Haemophilus influenzae, but the drug had a slightly higher MIC than those of a few oxime-type cephems already on the market. 2. CFMT was as stable as cefixime to beta-lactamase, generated by Moraxella subgenus Branhamella catarrhalis, which reduces the antimicrobial activity of cephems. 3. Blood concentrations of CFMT after administering cefetamet pivoxil (CFMT-PI), an oral form of the drug, exceeded the MIC80 against the "3 primary pathogens" as well as M. (B) catarrhalis and Klebsiella pneumoniae, for a duration of approximately 9 and 11 hours, respectively, after single doses of 250 and 500 mg. This suggests that CFMT could remain above the MICs for a sufficient time period with twice daily dosages of normal dose levels. 4. It is concluded that CFMT-PI will be useful for treating urban RTIs. PMID- 1494229 TI - [Therapeutic effects of cefuzonam against severe infections in patients with hematopoietic disorders. Hanshin Infection Study Group]. AB - Cefuzonam (CZON) was used to treat severe infections in 151 patients with hematopoietic disorders, and its efficacy and safety were assessed. The drug was given in doses of 2.0 to 6.0 g a day, divided into 2 or 3, intravenously by injection or infusion. The clinical effects were excellent in 34 cases, good in 40 cases, fair in 5 cases, and poor in 57 cases. Therefore, the results were excellent or good in 54.4% of the patients treated. The efficacy rates were 43.8 and 35.9% for groups of patients whose neutrophil counts were 500/microliters or less and 100/microliters or less, respectively. It was excellent or good in 70.6% of patients in whom causative agents were identified, and in 66.7 and 80.0% of patients infected with Gram-negative and -positive bacilli, respectively. The efficacy rate for patients infected with unidentified agents was 52.1%. The rate for patients who had received other antibiotics previously was 41.5%. The rate for patients having received only one antibiotic for the preceding treatment was 50.0%. Six (3.9%) of the treated patients experienced adverse effects including changes in laboratory test results observed in 4. PMID- 1494230 TI - [Pharmacokinetics of cefprozil in infant and adult beagle dogs]. AB - The Pharmacokinetics of cefprozil was studied upon oral administration of 25 mg/kg to fasted infant and adult Beagle dogs. When the pharmacokinetic parameters between infant and adult dogs were compared, the mean peak concentration (Cmax) in infant dogs (21.2 micrograms/ml) was significantly (P < 0.01) lower than that of adult dogs (27.8 micrograms/ml). But significant differences were not found in the areas under the concentration-time curve (AUC, in infant dogs: 121 micrograms.hr/ml, in adult dogs: 130 micrograms.hr/ml), half-lives (T 1/2, in infant dogs: 4.7 hours, in adult dogs: 4.7 hours) or urinary recovery rates (UR, in infant dogs: 36.3%, in adult dogs: 34.7%) between the 2 groups. These results suggest the distribution volumes of infant dogs are larger than those of adult dogs, and the absorption rates of infant dogs are slower than those of adult dogs, whereas the absorption quantities are similar. PMID- 1494231 TI - [The influence of cefprozil on intestinal bacterial flora]. AB - Cefprozil (CFPZ, BMY-28100), a new oral cephalosporin antibiotic, was studied for its effect on the intestinal bacterial flora in pediatric patients. The subjects were children admitted for infections (2 males and 2 females, 9 months to 6 years 3 months old, weighed 4.3 to 19.0 kg). CFPZ granule was orally administered at a dose between 10.0 to 11.6 mg/kg, 3 doses daily, over 4 to 14 days. The feces from these children were collected before, during and after administration, and bacteria were identified and counted. CFPZ concentration, beta-lactamase activity were also assayed. Bacterial flora in feces during CFPZ administration showed some variance, but no significant change was observed in main aerobes and anaerobes. And in no case, glucose nonfermentative Gram-negative bacilli or fungi were found dominant. beta-Lactamase activity was positive in the feces in all cases. CFPZ concentrations were not detectable in feces before, during and after administration. The above results suggest that CFPZ is a drug with little influence on the intestinal bacterial flora in children. PMID- 1494232 TI - [Pharmacokinetic study on oral antibiotics in pediatrics. III. A pharmacokinetic study on cefprozil in pediatrics]. AB - The absorption and excretion were studied in the field of pediatrics, and pharmacokinetic analyses were performed. 1. Influence of food: Cefprozil (CFPZ, BMY-28100) was given to 6 school children in a before and after meal cross over design. With before meal administration, Tmax was 1.11 +/- 0.08 hours, Cmax was 5.08 +/- 0.27 micrograms/ml, T 1/2 was 0.77 +/- 0.09 hour, and urinary recovery rate (0-8 hours) was 55.2 +/- 4.7%. With after meal administration, these values were 1.31 +/- 0.04 hours, 3.98 +/- 0.38 micrograms/ml, 0.72 +/- 0.03 hour and 46.3 +/- 9.0%, respectively. A shorter Tmax value was, obtained higher Cmax and more or less higher urinary recovery rate when the drug was administered before meal, hence the food was considered to influence the absorption of the drug. 2. Dose effect: CFPZ was given on empty stomach to 6 school children in doses of 7.5 mg/kg and 15.0 mg/kg in the cross over design. With the lower dose Cmax was 6.19 +/- 0.36 micrograms/ml and AUC was 14.90 +/- 1.02 micrograms.hr/ml, and with the higher dose they were 12.38 +/- 1.29 micrograms/ml and 28.56 +/- 1.79 micrograms.hr/ml. Dose effects appeared to exist for CFPZ. A higher urinary recovery rate was obtained at the dosage of 7.5 mg/kg (82.1 +/- 6.4%) compared to the dosage of 15.0 mg/kg (51.1 +/- 7.1%). 3. Influence of age: CFPZ was given on empty stomach to 17 school children, 19 younger children and 5 infants. Tmax were 1.07 +/- 0.09, 1.06 +/- 0.07, and 1.40 +/- 0.09 hours, respectively for the 3 groups, hence significantly longer Tmax was observed in infants. Cmax were higher in older children and they were 5.62 +/- 0.38, 4.72 +/- 0.53 and 4.05 +/- 0.33 micrograms/ml, in the 3 age groups, respectively. T 1/2 were 0.73 +/- 0.04, 0.78 +/- 0.09 and 0.98 +/- 0.12 hour, respectively, it was longer in infants. The AUCs were not different among the 3 groups, but different urinary recovery rates were obtained with higher recovery in school children, with values of 64.1 +/- 4.3, 44.3 +/- 3.8 and 51.6 +/- 3.3%, respectively. PMID- 1494233 TI - [Clinical evaluation of a new oral cephem, cefprozil in children]. AB - Cefprozil (CFPZ, BMY-28100) was evaluated for its efficacy, safety and pharmacokinetics in children. CFPZ was effective against streptococcal pharyngitis, pneumococcal lower respiratory tract infections, staphylococcal skin infections and Escherichia coli urinary tract infections, but was less effective against lower respiratory tract infections and otitis media due to Haemophilus influenzae. No adverse reactions were encountered in 46 cases treated with CFPZ. With a premeal administration of 7.5 mg/kg, the Cmax was approximately 3.2 micrograms/ml and the T 1/2 beta was 1.4 hours. From the present study, CFPZ appears to be safe and effective against community-acquired childhood infections. PMID- 1494234 TI - [Clinical studies on cefprozil granules in pediatrics]. AB - Cefprozil (CFPZ, BMY-28100) granules was administered to a group of pediatric patients. The new oral cephalosporin, CFPZ, was evaluated clinically in 42 pediatric patients, and a pharmacokinetic study was performed in 6 patients. Serum and urinary concentrations of CFPZ were determined in 6 patients who were given single dose of 7.5 or 15.0 mg/kg. Serum concentrations were determined at 1, 2, 3, 4 and 6 hours after dosing. Urinary concentrations were measured for periods of 0-6 hours after dosing. With oral administrations of 7.5 mg/kg and 15.0 mg/kg, peak serum concentrations were 2.13 micrograms/ml and 6.22 micrograms/ml, respectively, at 2 hours, and biological half-lives were 1.06 hours and 1.36 hours, respectively. Urinary recovery rates were 44.8% and 56.1%. The clinical evaluation was conducted in 41 patients including 16 patients with acute tonsillitis, 8 patients with lacunar tonsillitis, 4 patients with scarlet fever, 3 patients with acute bronchitis, 1 patient each with pertussis, furuncle, impetigo and lymphadenitis, and 6 patients with urinary tract infections. The ages of the patients were 10 month to 11 years 1 month, and they were treated with CFPZ at doses ranging 9.0-45.0 mg/kg daily for 3-14 days, the overall clinical efficacy rate was 92.7%. An eradication rate of 79.2% was achieved for 28 strains of 8 species identified in the patients. No side effects were observed. Abnormal laboratory test results obtained were eosinophilia in 2 patients. PMID- 1494235 TI - [Laboratory and clinical studies on cefprozil granules in pediatrics]. AB - Fundamental and clinical effects of cefprozil (CFPZ, BMY-28100) granules, a new oral cephalosporin antibiotic, in pediatric field were investigated. The result obtained were summarized as follows. 1. CFPZ (10% granules) was given to 1 child in a single dose of 7.5 mg/kg. The peak serum concentration of CFPZ was 4.51 micrograms/ml at 2 hours after administration. Half-life and AUC values were 0.98 hour and 20.7 micrograms.hr/ml. The mean peak urinary concentrations of CFPZ and 6 hours recovery rates were over 200 micrograms/ml at 2-6 hours and 27.6%, respectively. 2. Clinical efficacy of CFPZ was investigated in a total of 41 children, including 14 with upper respiratory tract infections, 6 with acute bronchitis and pneumonia, 2 with acute otitis media, 3 with skin and soft tissue infections and 16 with urinary tract infections. The clinical efficacy rate was 95.1%. The bacteriological eradication rate was 84.6%. 3. Two patients showed abnormal laboratory test results. One had elevations of both GOT and GPT, and another had eosinophilia which were attributed to this antibiotic as side effects. PMID- 1494236 TI - [Clinical study on cefprozil in pediatrics]. AB - Clinical efficacy and safety of cefprozil (CFPZ, BMY-28100), a newly developed oral cephalosporin, were studied in our pediatric department. Clinical effectiveness, bacteriological effectiveness and side effects were studied in 116 pediatric patients with ages ranging 4 months to 11 years. CFPZ was given 4.6 14.1 mg/kg daily in 3 times for 3-10 days. Clinical efficacies were evaluated in 112 patients, and the therapeutic effectiveness were excellent in 1 and good in 6 for 7 patients with acute pharyngitis, excellent in 24 and good in 26 for acute purulent tonsillitis, excellent in 3, good in 8 and fair in 1 for acute bronchitis, excellent in 21, good in 7, fair in 1 and poor in 1 for acute pneumonia, excellent in 1 acute purulent parotitis, excellent in 2 and good in 7 for acute UTI, good in 1 impetigo, fair in 1 periproctal abscess and good in 1 acute enteritis. The effectiveness rate was 96.4%. Bacteriologically, 4 strains of Staphylococcus aureus (beta-lactamase producing strains), 1 strain of Staphylococcus epidermidis (beta-lactamase producing strain), 2 strains of Streptococcus pneumoniae, 2 strains of Streptococcus agalactiae, 4 strains of beta-Streptococcus, 1 strain of Klebsiella pneumoniae (beta-lactamase producing strain) and 1 strain of Salmonella C2 were all disappeared, and of 22 strains of Streptococcus pyogenes, 20 strains were disappeared, 1 was decreased and 1 was unknown, of 5 strains of Escherichia coli (3 beta-lactamase producing strains), 4 were disappeared and 1 was decreased, of 29 strains of Haemophilus influenzae (14 beta-lactamase producing strains), 14 were disappeared, 11 were decreased, 3 persisted and 1 was unknown and of 2 strains of Haemophilus parainfluenzae (1 beta-lactamase producing strain), 1 was disappeared and 1 persisted. The bacteriological eradication rates for Gram-positive bacteria and Gram-negative bacteria were 97.1% and 56.8%, respectively, and the drug was especially effective against Gram-positive bacteria. No side effects nor refusal of ingestion were observed. As abnormalities in laboratory test results, 3 cases of elevation of eosinophil counts and 1 of elevation of platelet counts were observed. In conclusion, CFPZ was considered to be a safe and highly effective antibiotic in pediatric infections. PMID- 1494237 TI - [Laboratory and clinical studies on cefprozil in the field of pediatrics]. AB - Laboratory and clinical studies on cefprozil (CFPZ, BMY-28100), a new cephem antibiotic, were carried out in the field of pediatrics. The results obtained are summarized as follows: 1. Serum concentrations, urinary concentrations and urinary recovery rates of CFPZ were determined upon oral administration of CFPZ after meal at doses of 4 mg/kg granules in a case, 7.5 mg/kg granules in 2 cases and 15 mg/kg granules in one. Peak serum levels of CFPZ were obtained at an hour in 3 cases and at 2 hours in 1 case after administration of the drug with a range of 2.7-8.6 micrograms/ml with half-lives of 0.69-0.95 hours. Urinary recovery rates in the first 6 hours after administration ranged from 59.4-71.3%. 2. MICs of CFPZ against 36 clinical isolates (Staphylococcus aureus 4 strains, Streptococcus pneumoniae 5, Streptococcus pyogenes 5, Escherichia coli 5, Haemophilus influenzae 12, Haemophilus parainfluenzae 4, and Branhamella catarrhalis 1) were compared with those of cefaclor (CCL) and ampicillin (ABPC). The antibacterial activity of CFPZ was superior to those of CCL against Gram positive cocci, and to those of ABPC against E. coli, and was equal to those of CCL and inferior to those of ABPC against H. influenzae. 3. Thirty-seven pediatric patients with acute infectious diseases (pharyngitis/tonsillitis 17, bronchitis 7, pneumonia 3, skin and soft tissue infection 2, and urinary tract infection 8) were treated with CFPZ at daily doses of 10-47 mg/kg t.i.d. as a rule. The efficacy rates were 100% clinically and 56% bacteriologically. 4. Side effects or abnormal laboratory test values were not observed except for an increased platelet count in 1 case and elevated GOT, GPT values in 2 cases. PMID- 1494238 TI - [Pharmacokinetic, bacteriological and clinical studies on cefprozil in pediatric patients]. AB - Cefprozil (CFPZ, BMY-28100), a new oral cephem antibiotic, was studied for its antibacterial activities, absorption and excretion upon administration. Its clinical efficacies were also studied in pediatric patients with infections. A study on antibacterial activities of CFPZ against 11 clinical isolates including 6 species found that its activities against Staphylococcus aureus, alpha hemolytic Streptococcus, Escherichia coli and Haemophilus influenzae were equal or superior to those of CCL. When CFPZ was given to patients orally at 15 mg/kg, maximum serum concentration was obtained between 1 to 2 hours after administration and urinary excretion rate in the first 6 hours was 33.8 +/- 17.6%. Clinical evaluation was done in a total of 25 patients with various infections. Responses were excellent in 15 cases and good in 10 cases, hence the efficacy rate was 100%. As side effect, soft stool was found in 1 case, and eosinophilia in 2 cases and elevation of GOT and GPT in 1 case were found as abnormal laboratory test results, but none of them was serious. It appears that CFPZ is an effective and safe antibiotic in the field of pediatrics. PMID- 1494239 TI - [Laboratory and clinical studies of cefprozil in pediatric field]. AB - Laboratory and clinical studies were done on cefprozil (CFPZ, BMY-28100). The results are summarized as follows. CFPZ was administered through the oral route to 2 children at a single dose of 7.5 mg/kg. After administration, peak serum levels of CFPZ obtained in the 2 cases were 6.71 micrograms/ml at 1 hour and 6.45 micrograms/ml at 2 hours, respectively and half-lives were 1.28 hours and 0.92 hour, respectively. The urinary excretion rates of CFPZ were 58.9% and 59.4%, respectively. Treatment with CFPZ was made in 37 cases of pediatric bacterial infections: 1 case of pharyngitis, 16 cases of tonsillitis, 16 cases of scarlet fever, 3 cases of impetigo, 1 case of UTI. Results obtained were excellent in 24 cases, good in 13 cases. No significant side effects due to the drug were observed, except 1 case of loose stool, 3 cases of eosinophilia, and 1 case each of elevated GOT and GPT. PMID- 1494240 TI - [Overall clinical evaluation of cefprozil against infections in pediatric fields. Pediatric Study Group for Cefprozil]. AB - Cefprozil (CFPZ, BMY-28100) granule preparation was studied for pharmacokinetic, bacteriological and clinical aspects in the pediatric infections. The results obtained are summarized as follows: 1. Serum concentrations and urinary excretion. The pharmacokinetics of CFPZ in pediatrics was investigated by single oral administration of fine granules at doses of 4.0, 7.5 and 15.0 mg/kg. Peak blood levels of CFPZ were 3.06, 4.62 and 9.65 micrograms/ml, respectively, at 1.00-1.30 hours after each dose and AUCs were 7.44, 12.50 and 27.01 micrograms.hr/ml, respectively. These data showed that Cmax and AUC depended on dose levels. T 1/2 (beta) at these dose levels were 1.03, 0.94 and 1.01 hours, respectively. There were no differences related to dose. Urinary recovery rates in the first 6 hours after administration were 51.5-57.1%. The pharmacokinetics of CFPZ before or after meals were also investigated at a dose of 7.5 mg/kg. Peak blood levels were 4.88 micrograms/ml at 1.17 hours after administration in the fasting state, and 4.30 micrograms/ml at 1.54 hours after administration in the non-fasting state. Delay of Tmax and slight decrease of Cmax were observed in the non-fasting state, but T 1/2 and AUC were 0.91 hour and 12.96 micrograms.hr/ml, respectively, in the non-fasting state, and were similar to those in the fasting state, 0.93 hour and 12.82 micrograms.hr/ml, respectively. Urinary recovery rates in the first 6 hours after administration were 63.8% in the fasting state and 50.7% in the non-fasting state. 2. Clinical results. Clinical efficacies of CFPZ granules in various infectious diseases were studied in 804 cases. Twenty nine cases, mostly viral or mycoplasmal infections, were excluded from the statistical analysis. The clinical efficacy rate in 527 cases with causative bacteria isolated was 97.2%; and in 248 cases from whom no significant isolate had been obtained was 96.0%. The clinical efficacy rate in 475 cases with monobacterial infections (proven by culture of isolates) was 97.3%, and that in 52 case with polybacterial infections was 96.2%. Haemophilus influenzae was isolated mostly from acute respiratory infections. In 88 cases from whom H. influenzae was isolated, clinical efficacy rate was 95.5%. In cases from whom H. influenzae was found concomitant by with Staphylococcus aureus, Streptococcus pyogenes or Streptococcus pneumoniae, the clinical efficacy rates were also high. The bacteriological eradication rate in cases with 582 strains was 83.3%; the eradication rate for Gram-positive organisms was 95.8%; and for Gram-negative organisms, it was 64.2%.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1494241 TI - [Changes in DNA synthesis in lymphocytes induced by carbachol via muscarinic acetylcholine receptor in relation to aging and Alzheimer's disease in females]. AB - To investigate whether cellular DNA synthesis in lymphocytes can be induced by carbachol, we studied the effect of carbachol in cultures of peripheral lymphocytes. Three age groups of healthy female adults were examined: 40-49 (N = 10), 51-59 (N = 8), and 61-69 years old (N = 8). Moreover, we studied lymphocytes from 14 female patients (47-69 years old) with probable Alzheimer's disease. Lymphocytes were incubated for 72 hrs at 37 degrees C, with or without 5 mM carbachol. The effects of carbachol on the initiation of DNA synthesis in lymphocytes were determined by 24 hr-pulse-labeling with [3H]-thymidine ([3H] dT). Stimulation indexes (S.I.) were defined as the ratios of DNA synthesis induced with or without carbachol. In 37 out of 40 subjects, carbachol elicited an increase in [3H]-dT incorporation. Furthermore, carbachol induction of DNA synthesis was blocked by muscarinic antagonist, atropine. These data show that carbachol induces DNA synthesis in peripheral lymphocytes are well as the central nervous system, indicating that the proliferation is mediated by the muscarinic acetylcholine receptor. For healthy controls (age range 40-69 years old, N = 26), a negative correlation (r = -0.505, p < 0.01) was found between age and S.I. The regression equation was: Y = -0.575X + 142.1 where, X and Y designate the age of individuals and S.I., respectively. However, there were significant differences (p < 0.05) with S.I. between age groups 40-49 and 61-69 years old. For patients with Alzheimer's disease, no correlation was obtained between age and S.I.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1494242 TI - [The relationship between dietary ascorbic acid intake and serum lipid concentration in the aged]. AB - The aim of this study was to investigate the relationship between dietary ascorbic acid intake and serum lipid concentration in the aged. The amount of dairy food intake for three consecutive days were measured and the serum levels of total-cholesterol (TC), triglyceride (TG), HDL-cholesterol (HDLC) were determined 279 subjects (135 males and 135 females), 65 years and over living in one community. The LDL-cholesterol (LDLC) was calculated by (TC-HDLC)-TG x 0.2. Dietary ascorbic acid intake showed no significantly difference between males and females, but had a significantly positive correlation with HDLC, the intake of carbohydrates and protein and total fat. However it had a significantly negative correlation with LDLC and LDLC/HDLC. Multiple regression analysis showed that dietary ascorbic acid intake had a statistically significant relationship with HDLC, LDLC and LDLC/HDLC. Since HDLC, which is known to be an anti-atherogenic, was related to increase in the dietary ascorbic acid intake, and LDLC, which is known to be an atherogenic, was related to its decrease, it was suggested that dietary ascorbic acid intake might have an important effect on the genesis and prevention of atherogenic diseases. PMID- 1494243 TI - [Changes in blood pressure and pulse rate during visit to a doctor's office]. AB - Changes in blood pressure (BP) and pulse rate were measured during visits to a doctor's office by means of an non-invasive ambulatory BP monitoring device in 47 elderly hypertensive patients (mean age 73.0 years). Systolic BP increased from 140.5/85.4 mmHg to 157.9/85.7 mmHg immediately after entering the doctor's office and tended to return to the previous level at 5 minutes after entering although diastolic BP did not change during the visit. Pulse rate also increased slightly, but significantly on entering the office. The difference in BP between 25 minute before and just after entering an office was +17.4 mmHg in systolic. -0.1 mmHg in diastolic. If an increment in systolic BP more than 10 mmHg was defined as positive for white coat effect, they were observed in 59.6%. The frequency of white coat hypertension was 46.7% in the age of sixties, 65.2% in seventies and 66.7% in eighties but there was no significant difference among 3 groups. There was a tendency for white coat hypertensions to be more frequent in men compared than in women (p = 0.07). PMID- 1494245 TI - [Psychosomatic state of centenarians]. AB - A survey to investigate the psychiatric and physical characteristics of centenarians was conducted from 1987 to 1989 in the Tokyo metropolitan area with a team of psychiatrists and psychologists using a semi-structured interview form. In that 3-three period, out of 509 centenarians living in Tokyo, 294 persons and their caregivers (57.8%) including the 65 institutionalized centenarians were examined. Two hundred and fifteen centenarians were not able to be interviewed due to various reasons. Out of 294 centenarians, 76 persons (25.9%) were interviewed by telephone. Also out of these, 176 (59.8%) were living with their son's or daughter's family. Ten male centenarians (12.8%) were living with their wives, while no female was living with a spouse. Five men and four women were living alone. There was a marked difference of education in years between both sexes. Mean years of education were 10.2 in the male and 5.5 in the female. According to the Clinical Dementia Rating, 31.6% out of 218 centenarians interviewed were not demented and those with dementia were even distribution of mild, moderate and severe dementia. There were marked differences according to sex, similar to that found in ADL. Of 63 males, 46.0% were not demented, whereas 25.8% of 155 females were not demented. Only 3.2% of males were severely demented, but in females 27.1% showed severe dementia. HDS scores decreased in relation to the advance in severity of dementia. Approximately 27% of the cases had no previous physical histories; 21.8% for the male and 29.2% for the female.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1494244 TI - [Cerebral infarctions in elderly patients with anemia]. AB - The authors investigated the cause of cerebral infarctions in elderly patients with anemia. Among 411 patients with acute cerebral infarctions, eight patients showed anemia (Hb < 10 g/dl) at the time of stroke. Only 2 patients had strokes during hospitalization were aware of their anemias before stroke. They were classified into two groups. One was the sudden onset group (4 patients) of whom 3 had malignant tumors, and 2 showed disseminated intravascular coagulations (DIC). There were no patients with atrial fibrillation or cardiac disease. All patients showed cortical infarction, and two died soon after stroke. Autopsy revealed verruca formation of the mitral valve in one patient and thrombus in the right ventricle in another. We thought that non-bacterial thrombotic endocarditis (NBTE) was the major cause of cerebral infarctions in this group. The other group consisted of 4 cases of thrombotic stroke. Their neurological symptoms appeared to be progressive. They also showed cortical infarctions except for one case of pontine infarction. Severe stenosis of the cerebral arteries was revealed by angiography in two patients and by autopsy in one. We concluded that cerebral infarctions in elderly patients with anemia can be important signs of underlying malignant tumors in sudden onset strokes or cases of severe cerebral artery stenosis with thrombotic strokes. PMID- 1494246 TI - [Clinical characteristic of elderly patients with insulin-dependent diabetes mellitus]. AB - The number of elderly patients with insulin-dependent diabetes mellitus (IDDM) is increasing because of the prolongation of life due to the improvement of diabetic control. For better management of elderly patients with IDDM, we investigated the clinical and genetic characteristic of older patients with IDDM in comparison with younger patients. The subjects studied consisted of 19 patients with IDDM treated at the Department of Geriatric Medicine, Osaka University Hospital. Among the 19 subjects, 7 patients (37%) were more than 50 years old, including 3 patients (16%) more than 65 years old. The clinical and genetic characteristics of these 7 patients (older patients group) were compared with those of 12 patients (younger patient group) whose age was less than 50 years old. The age at onset of IDDM was significantly higher in older patient group (46 +/- 13 years old; mean +/- SD) than in younger patient group (34 +/- 6 years old). There was no significant difference in the duration of IDDM between older and younger patients (13 +/- 6 and 12 +/- 8 years, respectively). There were no significant differences in daily insulin dose, glycemic control (fasting plasma glucose and HbA1c levels) and glycemic stability as measured by the standard deviation of 10 measured fasting plasma glucose levels between the two groups. The frequency of diabetic retinopathy and neuropathy in the older patients was slightly, but not significantly, higher than that in younger patients. The frequency of diabetic nephropathy was similar in both groups.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1494247 TI - [Role of neutrophil and T cell functions in host defense mechanisms of the elderly]. AB - We studied neutrophil functions (phagocytosis, intracellular killing and chemotaxis with or without recombinant human granulocyte-macrophage colony stimulating factor (rhGM-CSF) and T cell functions (lymphocyte proliferation and production of GM-CSF in response to phytohemagglutin (PHA)) to clarify host defense mechanisms in the elderly. There was no significant difference in phagocytic activity of neutrophils between the elderly and control young adults. rhGM-CSF enhanced phagocytosis by neutrophils, and a similar degree of enhancement was obtained in both groups. Killing activity of neutrophils evaluated by the new Nitroblue tetrazolium reduction test in the elderly was significantly lower than that in young adults (p < 0.001), however, pretreatment of neutrophils with rhGM-CSF resulted in an increase of killing activity in the elderly, raising their response to a level comparable to that of young adults pretreated with rhGM-CSF. There was no significant difference between the elderly and young adults in chemotaxis of neutrophils. rhGM-CSF alone did not prime chemotaxis, but primed chemotaxis in response to chemoattractant (N-formyl methionyl-leucyl-phenylalanin) in both individuals. Lymphocyte proliferation and production of GM-CSF in response to PHA in the elderly were significantly lower than those in the young adults (p < 0.001, p < 0.05, respectively). These results indicated that impaired T cell functions may contribute, at least in part, to susceptibility to bacterial infection in the elderly. PMID- 1494248 TI - [The relationship between fecal kinetics and body temperature in elderly people]. AB - The relationship between fecal kinetics and body temperature was examined in elderly people. The subjects consisted of 34 hospitalized patients over 65 years of age (11 males aged 66-82 years, with a mean age of 70.3 years; and 23 females aged 65-84 years, with a mean age of 72.1 years). Then mean age of all subjects was 71.5 years. The subjects were divided into two groups: the non-constipation (NCP) group (patients who had been evacuating at least once daily) and the constipation (CP) group (patients who had not evacuated for 3 days or more). In the CP group, we analyzed the lowest and highest body temperature during two consecutive days (the day of evacuation and the previous day) and the lowest body temperature during another two days (the day of evacuation and the following day). In the NCP group, 3 consecutive days were selected at random for analyzing the lowest body temperature on the first day, the highest body temperature on the second day and the lowest body temperature on the third day. In the CP group, the body temperature before evacuation was 37.3 degrees C or more in 6 of the 28 patients (21.4%). In the NCP group, the highest body temperature before evacuation averaged 36.39 degrees C and the lowest body temperature after evacuation averaged 36.0 degrees C, with a temperature difference of 0.39 degrees C between the pre- and post-evacuation periods.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1494249 TI - [Prediction of nocturnal desaturation in elderly patients with chronic respiratory disease]. AB - Previous reports suggest that nocturnal disorders of sleep and breathing have increased prevalence among the elderly, and episodic nocturnal oxygen desaturation (NOD) has an increased incidence in patients with chronic respiratory disease. Current Japanese criteria for home low flow oxygen therapy (LFOT), recommend LFOT for patients with daytime PaO2 < 55 torr or with daytime PaO2 < or = 60 torr who have significant NOD. Strict adherence to these LFOT criteria requries full overnight monitoring of arterial oxygen saturation (SaO2) in all patients with daytime PaO2 < or = 60 torr. Since widespread nocturnal oximetry involves significant expenditure of time and resources, it is important among patients with chronic respiratory diseases to predict those who will have significant NOD. The aim of the present study was to formulate criteria for identification of patients who are most likely to demonstrate significant NOD based upon daytime respiratory function data. Subjects included 34 elderly patients with daytime PaO2 > or = 55 torr, who had stable severe chronic respiratory disease (15 chronic emphysema, 6 chronic bronchitis, 12 post tuberculosis, and 1 kyphoscoliosis). Study data included medical history, assessment of dyspnea by Hugh-Jones classification, and measurement of daytime, awake arterial blood gases and spirometry. Each subject underwent full overnight oximetry monitoring. The percentage of total sleep time recorded with SaO2 < or = 85% was noted (DST85), and NOD was defined as DST85 > or = 1%. Of the 34 patients, 11 were identified as NOD, and 23 as non-NOD patients. Duration and severity of dyspnea were not different between NOD and non-NOD patients.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1494250 TI - [Two cases of adult onset of Still's disease in the elderly]. AB - Two cases of adult onset of Still's disease is in a 83-year-old and a 61-year-old women. Both cases complained of high fever, arthralgia, sore throat and maculae. Examinations on admission revealed leukocytosis and negative antinuclear antibody. Administration of prednisolone resulted in improvement of the clinical symptoms and laboratory data. In general, the onset of this disease is usually in early adulthood, but in these two cases the onset was at an advanced age. These results suggest that Still's disease of adult onset should be included in the differential diagnosis of fever of unknown origin, if the patient is elderly. In the treatment of the disease, proper attention to side effects of prednisolone and complications can be important. PMID- 1494251 TI - [Improvement of respiratory function with weight reduction in obese elderly]. AB - The patient was a 74-year-old woman who had been obese since age 18. Her obesity was refractory to dietary manipulation. She had been suffering from increasing dyspnea for several months and eventually could not even move. She was admitted to a hospital and diagnosed as having heart failure. Although her cardiac function recovered with medical treatment, her symptoms did not improve. The patient was then sent to our hospital. On admission, her height and weight were 149 cm and 81.9 kg, respectively, yielding a body mass index (BMI) of 36.6 kg/m2. Arterial blood gas analysis in room air revealed hypoxemia and an apnea index of 27 per hour. She was given a daily 500-1000 kcal diet. After four months of treatment, her weight decreased to 65 kg with a BMI of 29.3 kg/m2. Weight reduction together with the usage of progesterone-derivatives resulted in marked improvement of sleep apnea. The apnea index decreased to 3/h and arterial blood gas values normalized. This patient seemed to have suffered from both obesity hypoventilation syndrome and sleep apnea syndrome. Improvement of respiratory function was achieved through relief of airway obstruction and weight reduction, with activation of the respiratory center due to progesterone treatment. PMID- 1494253 TI - [A new payment model is necessary]. PMID- 1494252 TI - [Elderly non-Hodgkin's lymphoma presenting with pulmonary squamous cell carcinoma as a complication of chemotherapy for malignant lymphoma]. AB - The authors report a case of pulmonary squamous cell carcinoma which occurred after chemotherapy of non-Hodgkin's lymphoma (NHL). A 76-year-old man, who was admitted to our department because of swelling of cervical lymph nodes, was diagnosed as having NHL (follicular mixed cell lymphoma). He was treated with 11 courses of CHOP therapy. Thereafter, chemotherapy including ifosfamide was carried out for approximately three years. In June, 1991, he was readmitted to our department because of swelling and pain in his left thigh and an abnormal shadow on chest X-ray. Chest CT demonstrated a cavitated shadow (about 5 cm in diameter) with an irregular margin in right S1, which was suggested to be lung cancer or pulmonary infiltration of malignant lymphoma. Bronchoscopy, which was carried out on July 12, showed bloody sputa from the right B1 ramus and markedly reddened mucosa at the orifice of the right upper bronchus. Sputum cytology revealed no malignancy. ACVP-16 chemotherapy including ara-C, CBDCA and VP-16 was initiated on July 14 because of enlarged superficial lymph nodes. On July 18, he fell out of bed and fractured his left femur. He also suffered from respiratory failure. He died of pulmonary haemorrhage on July 26. Autopsy revealed pulmonary squamous cell carcinoma. The occurrence of pulmonary squamous cell carcinoma is rare after the chemotherapy of malignant lymphoma. PMID- 1494254 TI - [Rude force--the most painful of all possibilities]. PMID- 1494255 TI - [Continuing education within the Grisons section of the Swiss Nursing Association in cultivation of relationships and the creation of milieu. "Everything starts with relationships"]. PMID- 1494256 TI - [How to act in case of a death. The craft of nursing]. PMID- 1494257 TI - [They are saving--not only in the Canton Berne--enough!]. PMID- 1494258 TI - [On the Federal vote from December 6, 1992: for and against joining the European Economic Community]. PMID- 1494259 TI - [My work place. "How can I help you?"]. PMID- 1494261 TI - [A rapidly expanding technique. Manual lymph drainage]. PMID- 1494260 TI - [The Ericsonian approach to pain control. Pain is my business]. PMID- 1494262 TI - [A psychiatric patient answers her nurse. When will we achieve a more human psychiatry?. Interview by Ria Frick]. PMID- 1494263 TI - [Profession: nurse]. PMID- 1494264 TI - [Running as a therapeutic instrument (Part 1). Running towards health]. PMID- 1494265 TI - Oral motor control, posturing, and myofunctional variables in 8-year-olds. AB - One hundred thirty-three rural second graders were evaluated for diadochokinetic abilities and myofunctional variables. Single-syllable diadochokinetic rates were significantly correlated with open-mouth resting postures. Slow trisyllable diadochokinetic rates were significantly correlated with a dentalized resting tongue posture and dentalized swallow patterns. The implications of these relationships are discussed. PMID- 1494266 TI - Glottal gap configurations in two age groups of women. AB - The purpose of this study was to gather data on glottal gap configurations in two age groups of women. Using videostroboscopy, glottal closure patterns of 20 women (10 young, 10 elderly) were observed across nine pitch/loudness conditions. While both young and elderly speakers displayed a high incidence of glottal gaps, the two groups differed markedly in the configuration of the gaps observed and in the phonatory conditions under which gaps were observed. Young speakers demonstrated posterior chink and incomplete closure significantly more frequently than elderly women, although rarely demonstrating anterior gap or spindle configuration. In contrast, anterior gap was the single most common type of gap in the elderly, with spindle also occurring significantly more frequently. Individual elderly speakers, overall, changed glottic configuration more frequently across phonatory conditions than did young speakers. Some individual elderly speakers tended to vary glottic configuration consistently with pitch level changes. PMID- 1494267 TI - Gradations in a pattern of neuromuscular activity associated with stuttering. AB - EMGs were recorded from muscles of the lip, jaw, and neck during conversational speech of 17 stuttering subjects. Averaged power spectra and coherence between pairs of EMGs were computed. Results indicate that tremorlike oscillations in the range of 5-15 Hz and high amplitudes of EMGs occupy a common continuum of motor patterns that may occur in stuttering. In subjects whose results fell at the strong end of this continuum, stuttered speech was distinguished by widely distributed, high-amplitude oscillations and relatively high coherence at the frequency of oscillation. At the other extreme, neither oscillatory activity nor amplitude was greater for stuttered speech; in fact stuttered and fluent speech were often associated with approximately equal EMG amplitude. These results suggest that there is not a single set of physiological events that uniformly characterize stuttering in all individuals; rather, events such as the occurrence of high-amplitude oscillations occur at different strengths in different individuals. PMID- 1494268 TI - Disfluencies in the conversations of young children who stutter: some answers about questions. AB - Parents of children who stutter are often advised to reduce the number of questions they ask their children. Implicit in this advice is the assumption that children who stutter will be more disfluent when answering questions. This study assessed parent-child conversational speech for 8 parent-child pairs to determine the relative amounts of disfluency in the child's responses to questions versus making assertions. Length and complexity of the children's utterances and the frequency of the parents' requests by level of demand were also evaluated. Results suggested that the responses made by the children to their parents' requests were significantly less likely to contain disfluencies than were their assertions. Also, longer and more complex utterances were more likely to contain disfluencies, regardless of their designation as assertions or responses. Parents were shown to favor request types of lower levels of demand in conversations. Requests posed with greater levels of demand were somewhat more likely to yield disfluent responses than were those at a lower demand level. PMID- 1494270 TI - Speech breathing in senescent and younger women during oral reading. AB - Breathing patterns in 20-30-year-old and 60-70-year-old women were recorded noninvasively during various nonspeech and oral reading tasks. On the nonspeech tasks, the only significant difference between groups was a smaller mean vital capacity for the older women. On oral reading, the older women had significantly greater means for absolute and relative inhalatory volumes, relative inhalatory airflow rates, absolute and relative volumes during nonphonatory exhalations, and relative exhalatory volumes. No significant mean differences between groups were found on absolute inhalatory airflow rates, absolute exhalatory volumes during speech, and absolute and relative exhalatory airflow rates. In both age groups, increases in sentence length were associated with significantly increased inhalatory and exhalatory volumes but mean airflow rates were not significantly affected by sentence length. Some differential effects of reading context on only the older group seemed to represent additional demands placed on their respiratory systems for speech breathing. PMID- 1494269 TI - Tongue strength and endurance: relation to highly skilled movements. AB - Tongue strength and endurance (fatigue) were examined in subjects who have acquired high skill levels with their tongues (supranormal) and in subjects who use the tongue normally. The supranormal groups were trumpet players and high school debaters who were able to speak intelligibly at rates much faster than normal. Hand strength and fatigue were also assessed. Maximal strength was measured by recording how much pressure an individual could exert on an air filled bulb. Endurance was measured by determining how long subjects could sustain 50% of their maximal pressure. Results showed that maximal strength of the tongue and hand did not differentiate the supranormal subjects from the normal subjects. Hand endurance did not differentiate the subjects either. However, the supranormal groups had significantly longer tongue endurance times than did the normal subjects. PMID- 1494271 TI - Speaking rates, response time latencies, and interrupting behaviors of young stutterers, nonstutterers, and their mothers. AB - The purpose of this study was to investigate the speaking rates, interrupting behaviors, and response time latencies (RTL) produced by stuttering and nonstuttering children and their mothers, and the relationship these three paralinguistic behaviors have to children's speech disfluencies. Subjects were 13 boys who stutter (mean age = 4:0) and their mothers and 13 nonstuttering boys (mean age = 4:0) and their mothers. No significant differences were found between the two groups of children or between the two groups of mothers for any of the three paralinguistic behaviors with the exception that the mothers of nonstuttering children exhibited significantly (p < 0.01) faster rates of speech than either group of children. A strong positive correlation (r = .84) was found between stuttering children's scores on the Stuttering Severity Instrument (Riley, 1980) and the durations of the overlapping portions of their mothers' interruptions (i.e., their simultalk). Findings of this study are taken to support a facilitative demands-capacities model of conversational interaction in which mothers adjust the demands of their speaking models in response to their children's demonstrated capacities for fluent speech production. PMID- 1494272 TI - A questionable consistency: response to Fitch (1990) PMID- 1494273 TI - Attitudes toward nonspeaking individuals who use communication boards. PMID- 1494274 TI - Modifications in sign under conditions of impeded visibility. AB - This study investigated the effects of reduced visibility on the distance of signing hands from the bodies of adult signers who are deaf and on their rates of sign production. Subjects were videotaped as they signed with partners in each of three experimental conditions: unimpeded, moderately impeded, and severely impeded visibility. Visual impedance was created by placing screens between signing partners. The distance of a hand from the body, in terms of lateral, vertical, and forward-depth dimensions, was determined from digitized measurements of single video frames randomly selected from those in which the subject was actively signing. Sign rate was calculated as the number of signs produced in a given segment of time. Signs produced in the severely impeded visibility condition were found to be made at a slower rate and with a mean hand position further forward and vertically higher than signs produced in the unimpeded visibility condition. PMID- 1494276 TI - Evaluating memory wallets in conversations with persons with dementia. AB - The use of memory wallets to self-prompt factual information during prompted conversations with familiar partners was evaluated for 9 subjects with dementia. Memory wallets contained 30 pictures and sentences about familiar persons, places, and events that each participant had difficulty remembering. The amount of training by caregivers was the one component of the intervention package that varied among the nine attempts to replicate condition effects observed on introduction of the wallets. All subjects learned to use the memory wallets to improve their conversations by making more accurate factual statements. Even when caregiver training was not provided to 3 subjects, condition effects were still demonstrated, with only 1 subject requiring a brief orientation to his wallet. Long-term maintenance of condition effects was demonstrated for 3 subjects up to 30 months' postintervention. These results support the clinical utility of a memory wallet intervention package for persons with dementia and provide preliminary evidence that often little more than preparing memory wallets and providing a brief orientation are required to facilitate their use in improving conversations with familiar conversational partners. PMID- 1494275 TI - Communicative gestures in children with delayed onset of oral expressive vocabulary. AB - Use of communicative gestures in a group of children with delayed onset of expressive oral vocabulary (late talkers) was compared with such use among normal language-matched controls and age-matched controls. Analyses revealed that late talkers used significantly more communicative gestures and for a greater variety of communicative functions than did language-matched controls. However, a 1-year follow-up revealed that 4 of the late talkers remained delayed (truly delayed late talkers) and 6 caught up (late bloomers). Reanalyses of Year 1 data based on these follow-up outcomes demonstrated that only late bloomers used more communicative gestures than did language-matched controls. Truly delayed late talkers did not differ from language-matched controls either for number of gestures, type of gestures (symbolic vs. nonsymbolic), or number of different functions for which gestures were used. Late bloomers also used more communicative gestures than did age-matched controls, suggesting that they (the late bloomers) were using gestures to compensate for their small oral expressive vocabulary. Results are discussed in the context of early predictors of risk for language impairment and relationships between language and cognition. PMID- 1494277 TI - The effects of auditory and visual interference on speech and sign. AB - Hearing adults produced signed and spoken monologues under conditions of quiet or 80 dB SPL of noise and with their vision unobstructed or obstructed. Their signs were videotaped and a random sample of 24 frames was analyzed in each condition through a computer program that determined the overall distance of the hand from a marker placed on the signer's torso. Vocal intensity was digitized from the tape recordings and analyzed by computer for 1 min of continuous speech in each condition. The visual obstruction had no effect either on the distance of the signs or on the vocal intensity of their speech. The subjects increased vocal intensity by about 55% when the noise was introduced (the usual Lombard effect), but the noise had no effect on the distance of the signs. Sign performance was not influenced by visual feedback, and sign and speech were independent communication systems, even in bilingual speaking and signing subjects. PMID- 1494279 TI - Then as an indicator of deictic discontinuity in adults' oral descriptions of a film. AB - An analysis of film descriptions of 20 normal-language adults revealed the adults' selective and systematic use of the word then. Then served to indicate an upcoming shift in discourse deixis. It occurred in clauses that told of a shift to a different discourse frame (conversation vs. story world of the film), to a new scene location, to a different character, and a shift in who was doing the viewing. The regularity in the use of then is taken to be evidence that speakers conceptualize their descriptions as being located in a variety of related frames, all having to do with the perspective taken on the current talk. A conceptual model underlying the speakers' use of then would need to include distinctions between the conversational and story world, the various scenes in the objective world of the story, and various subjective views that different observers can have when experiencing the described events. The results are taken as support for viewing discourse discontinuity as an important factor in discourse analysis. PMID- 1494278 TI - Effects of speech output type, message length, and reauditorization on perceptions of the communicative competence of an adult AAC user. AB - The effects of speech output type, aided message length, and partner reauditorization on naive observers' perceptions of the communicative competence of an adult augmentative and alternative communication (AAC) system user were examined. Subjects consisted of 48 naive adults with minimal exposure to nonspeaking persons. Eight scripted videotaped conversational conditions involving an AAC user and a normal-speaking partner were employed in the manipulation of the three independent variables. A balanced incomplete block design was used. Following each viewing, subjects completed a questionnaire designed to assess the communicative competence of the AAC user. Results indicated a significant main effect for aided message length only. Ratings of the AAC user were higher in conditions with phrases than in conditions with single word messages. Of interest was the finding that the use of digitized versus synthesized speech output had no effect on observer ratings. Clinical implications are discussed. PMID- 1494280 TI - Speech perception and production skills of students with impaired hearing from oral and total communication education settings. AB - This study examined the degree to which students with profoundly impaired hearing who had been educated in oral and total communication (TC) environments developed auditory and speech skills. The sample consisted of 227 16- and 17-year-old students with profoundly impaired hearing: 127 from TC programs (63 with normal hearing parents and 64 with deaf parents) and 100 from oral programs. Subject groups were matched in terms of age, unaided residual hearing, and IQ. On average, students from oral programs acquired more intelligible speech and made significantly better use of their limited residual hearing than did the TC students. This finding held for all TC students--those with deaf parents as well as those with normal-hearing parents. Although results of this study indicate that auditory and speech production skills are comparatively well developed in students who have consistently used spoken language throughout the day as the primary means of communicating, other factors associated with this oral sample, such as early amplification, consistent hearing aid use, early education, and parental support, may also be necessary for the development of good spoken language skills. PMID- 1494281 TI - Aging and the binaural advantage in reverberation and noise. AB - The consonant identification ability of younger normal-hearing adults and older adults with little or no peripheral hearing loss was assessed using monaural and binaural presentation in four listening conditions: quiet, noise, reverberation, and reverberation + noise. Performance was examined in terms of identification accuracy and amount of binaural advantage. Results suggest that the small amount of hearing loss in the older subjects limited their perception of distorted consonants. Neither age nor peripheral hearing loss was related strongly to the amount of benefit obtained from binaural presentation. PMID- 1494282 TI - Sustained benefits of hearing aids. AB - This study was designed to evaluate long-term benefits of hearing aids in elderly individuals with hearing loss. A primary care cohort of 192 elderly, hearing impaired veterans (mean age 72 +/- 6, 97% White, 94% retired) were assessed at baseline and at 4, 8, and 12 months after hearing aid fitting. Drop-out rates at 4, 8, and 12 months were 5%, 13%, and 16%, respectively. Outcome assessments included several quality-of-life scales: Hearing Handicap Inventory in the Elderly (HHIE), Quantified Denver Scale of Communication Function (QDS), Geriatric Depression Scale (GDS), and the Short Portable Mental Status Questionnaire (SPMSQ). All quality-of-life areas improved significantly from baseline to 4-month post-hearing aid fittings (p < 0.05). Social and emotional (HHIE), communication (QDS), and depression (GDS) benefits were sustained at 8 and 12 months, whereas cognitive changes (SPMSQ) reverted to baseline at 12 months. We conclude that hearing aids provide sustained benefits for at least a year in these elderly individuals with hearing impairment. PMID- 1494283 TI - Contributions of the fundamental, resolved harmonics, and unresolved harmonics in tone-phoneme identification. AB - Researchers describe Mandarin Chinese tone phonemes by their fundamental frequency (Fo) contours. However, tone phonemes are also comprised of higher harmonics that also may cue tone phonemes. We measured identification thresholds of acoustically filtered tone phonemes and found that higher harmonics, including resolved harmonics above the Fo and unresolved harmonics, cued tone phonemes. Resolved harmonics cued tone phonemes at lower intensity levels suggesting they are more practical tone-phoneme cues in everyday speech. The clear implication is that researchers should use the Fo only as a benchmark when describing tone phoneme contours, recognizing that higher harmonics also cue tone phonemes. These results also help explain why tone-language speakers can identify tone phonemes over a telephone that attenuates selective frequencies, and suggests that hearing impaired tone-language speakers may still identify tone phonemes when their hearing loss attenuates selective frequencies. PMID- 1494284 TI - Modulation detection, modulation masking, and speech understanding in noise in the elderly. AB - Temporal processing of suprathreshold sounds was examined in a group of young normal-hearing subjects (mean age of 26.0 years), and in three groups of older subjects (mean ages of 54.3, 64.8, and 72.2 years) with normal hearing or mild sensorineural hearing loss. Three experiments were performed. In the first experiment (modulation detection), subjects were asked to detect sinusoidal amplitude modulation (SAM) of a broadband noise, for modulation frequencies ranging from 2-1024 Hz. In the second experiment (modulation masking), the task was to detect a SAM signal (modulation frequency of 8 Hz) in the presence of a 100%-modulated SAM masker. Masker modulation frequency ranged from 2-64 Hz. In the final experiment, speech understanding was measured as a function of signal to-noise ratio in both an unmodulated background noise and in a SAM background noise that had a modulation frequency of 8 Hz and a modulation depth of 100%. Except for a very modest correlation between age and modulation detection sensitivity at low modulation frequencies, there were no significant effects of age once the effect of hearing loss was taken into account. The results of the experiments suggest, however, that subjects with even a mild sensorineural hearing loss may have difficulty with a modulation masking task, and may not understand speech as well as normal-hearing subjects do in a modulated noise background. PMID- 1494285 TI - Operant response in infants as a function of time interval following signal onset. AB - This study investigated the hypothesis that estimates of infant auditory threshold are lowered by extending the duration of individual test trials such that infants have more time to detect and respond to the acoustic signal. Forty 8 and 12-month-old infants were evaluated with an operant procedure to determine response latencies at four near-threshold levels. Resulting data were used to estimate the effect of trial duration on threshold by calculating the response performance that occurred at several intervals following signal onset. Findings indicate that most detection responses occurred in the initial 4 sec of the test trial, and use of an 8-sec trial interval yielded little gain in performance. The data reflect an insignificant shift (< 5.0 dB) in threshold as a function of extended trial intervals. PMID- 1494286 TI - Hepatocyte function in a hollow fiber bioreactor: a potential bioartificial liver. AB - We have developed a novel hepatocyte loaded hollow fiber bioreactor as a potential bioartificial liver. Freshly harvested rat hepatocytes were entrapped in a three-dimensional gel matrix within hollow fibers in a perfused bioreactor. Gel entrapment allowed cells to be cultured at high density while maintaining tissue-specific function. Hepatocyte function was evaluated in 10 bioreactors, each containing approximately 5 x 10(7) cells. Oxygen consumption averaged 0.32 pmole/cell/hr, albumin appearance averaged 0.60 pg/cell/hr, and lidocaine clearance (a measure of the P-450 activity) averaged 0.74 pg/cell/hr. Function persisted for the 7 days of the study. Electron microscopy at 7 days showed the distinctive ultrastructure of viable, differentiated hepatocytes: bile canaliculi, intercellular junctions, peroxisomes, abundant mitochondria, and glycogen granules. Maintenance of tissue specific function and ultrastructure suggests that this bioreactor configuration has potential as a device to support patients in liver failure, as well as to study hepatocytes in vitro. PMID- 1494287 TI - Inhibition of intimal hyperplasia by photodynamic therapy using photofrin. AB - Photodynamic therapy using photofrin and light energy inhibits human myofibroblast proliferation in cell culture. The purpose of this study is to evaluate its influence on intimal hyperplasia in vivo. Twenty New Zealand White rabbits underwent a standardized intimal injury to both common carotid arteries with a 2 Fr balloon catheter. One week later, half of the animals received photofrin (5 mg/kg) intravenously. The remaining 10 rabbits received no photofrin. Two days later, all neck incisions were reopened and a 1-cm segment of each of the 40 carotid arteries was exposed for 5 min to 80 mW of 630 nm light energy from a continuous wave tunable dye laser (fluence = 7.6 J/cm2). All vessels were harvested 5 weeks post-laser treatment following in vivo fixation with formalin. From each artery, separate cross-sections taken from both the lasered and non-lasered regions of each vessel were mounted and stained for histologic evaluation. Analyzed segments were then divided into four different treatment groups: group I segments consisted of arterial cross-sections which were taken from vessel regions that were injured but received neither photofrin nor laser treatment (group I, n = 20); group II segments also did not receive photofrin but were exposed to light energy (group II, n = 20); group III segments received photofrin but no light energy (group III, n = 20); and cross-sections in group IV were taken from those segments which received both photofrin and laser treatment. Using planimetry, the ratio of the area of intimal hyperplasia (IH) to the area enclosed by the internal elastic lamina (IEL) was measured for each specimen (IH/IEL).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1494288 TI - In vivo microscopy of rat skeletal muscle after ischemia using labelled neutrophils (PMN). AB - Neutrophils (PMN) have been implicated as mediators of the "no-reflow" phenomenon seen in skeletal muscle during reperfusion after ischemia. In order to evaluate the PMN contribution to the changes seen in the microcirculation of skeletal muscle after ischemia, we evaluated PMN velocity using in vivo microscopy in a rat model. After the induction of anesthesia, the right iliac and femoral arteries were isolated. The right anterior tibialis muscle was exposed in situ, covered with a plexiglass disc, and perfused with Kreb's solution. Fluorescein labeled bovine albumin was given intravenously, which identified the capillaries under microscopic magnification as viewed on the video screen. Acridine orange was then administered intravenously, which selectively fluoresced the PMN. The right iliac and femoral arteries were clamped for ischemia intervals of 5, 10, 15, 20, 25, and 30 min. Acridine orange was given immediately after the arteries were unclamped, after 30 min of reperfusion and after 60 min of reperfusion. PMN velocity was determined by the distance traveled by the PMN over time using the videotape and frame-by-frame review. Results demonstrated no change in PMN velocity (mm/sec) after 5 min of ischemia. After 10, 15, and 20 min of ischemia, PMN velocity initially slowed and then recovered, which was not statistically significant. After 25 min of ischemia, PMN velocity decreased significantly, which persisted (P < 0.05 compared to 5-min ischemia by ANOVA). No flow was seen after 30 min of ischemia.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1494289 TI - Selective lipoxygenase inhibitor reduces bile acid-induced gastric mucosal injury. AB - Leukotriene receptor blockade attenuates topical bile acid-induced gastric mucosal injury, suggesting that peptidyl-leukotrienes may be mediators of this injury. The purpose of this study was to test the hypothesis that a selective 5 lipoxygenase inhibitor protects against bile acid-induced gastric epithelial injury in the rat. Prior to injury with 10 and 20 mM acidified taurocholate (pH 1.2), rat stomachs were pretreated with either vehicle or WY50295K (selective 5 lipoxygenase inhibitor, 20 mg/kg). Injury was assessed by measuring net transmucosal hydrogen ion flux, luminal appearance of DNA, and gross mucosal injury. Topical 5-lipoxygenase inhibitor significantly reduced luminal H+ ion loss, surface epithelial cell loss (as measured by luminal accumulation of DNA), and gross mucosal injury in bile acid-injured stomachs compared to controls. This study lends further support to the hypothesis that leukotrienes may be mediators of bile acid-induced gastric mucosal injury. PMID- 1494291 TI - Collateral blood flow from skeletal muscle to normal myocardium. AB - Collateral blood vessels from skeletal muscle to myocardium might supplement intramyocardial collaterals during periods of acute myocardial ischemia. This study was conducted to verify the existence of such collaterals and to measure their contribution to collateral flow. In 12 male goats, the innate coronary collateral system to a moderate size myocardial risk area was defined with colored microspheres, and a latissimus dorsi pedicle flap was then apposed to the heart. After 3 weeks, skeletal muscle to myocardial collaterals were characterized by (a) creation of vascular casts (three animals); (b) estimation of skeletal muscle to myocardial collateral blood flow (three animals); and, (c) measurement of total collateral blood flow to the risk area (innate plus skeletal muscle to myocardial collateral flow). Under a dissecting microscope the vascular casts revealed direct communications from the skeletal muscle which penetrated deeply into the myocardium. With the coronary artery to the risk area open, the estimated myocardial collateral blood flow derived from the muscle flap was 0.01, 0.02, and 0.04 ml/min. With the coronary artery to the risk area closed, there was no significant increase in total coronary collateral blood flow. Although the quantity of blood flow delivered by skeletal muscle collaterals was small, this study demonstrates that clearly identified collateral blood vessels form between skeletal muscle and myocardium in a cardiomyoplasty model. This raises the possibility that, under conditions more favorable to their development, extramyocardial collaterals from skeletal muscle might be exploited to augment the intramyocardial collateral system. PMID- 1494290 TI - Systemic and local toxicity in the rat of methyl tert-butyl ether: a gallstone dissolution agent. AB - Methyl tert-butyl ether (MTBE) is an organic solvent that has been used to dissolve gallstones via a percutaneous transhepatic catheter into the gallbladder. To test whether MTBE might cause serious tissue injury if accidentally infused outside the gallbladder, the effect of MTBE (0.2 ml/kg) injected into the hepatic parenchyma, or administered intravenously or intraperitoneally, was examined in the rat. The toxicity of isopropyl acetate (IPA), an organic solvent with a similar chemical structure, was examined similarly. Intracaval injection of MTBE caused the highest mortality (100%). Mortality was less (59%) after intrahepatic injection and still less (17%) after peripheral vein injection. Most animals died instantaneously from cardiorespiratory arrest. Almost all animals that were injected with MTBE intrahepatically or intravenously showed localized areas of congestion, hemorrhage, and interstitial edema in the lungs. These changes were more severe in rats which survived for 24 hr than in those which died sooner. In those rats receiving intrahepatic injections, most rats which survived for 24 hr had liver necrosis at the site of injection. Intraperitoneal injection of MTBE produced 100% survival with only 1/5 rats showing a mild pulmonary injury at autopsy. IPA had toxic effects similar to those evoked by MTBE. To test whether tumor necrosis factor was involved in organ injury, serum levels were measured; they remained unchanged. These experiments indicate that two organic solvents, MTBE and IPA, are cytotoxic to local tissues and cause severe, and often fatal, lung damage when infused into a central vein. Less toxicity occurred if solvents were given into a peripheral or portal vein or intraperitoneally.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1494292 TI - The role of myoneural and luminal continuity in the coordination of canine gastroduodenal patterns of motility. AB - Our aim was to determine the role of intrinsic myoneural and enteric luminal continuity in the coordination of gastric and duodenal motility patterns. Three groups of dogs were prepared: five dogs with an intact gastrointestinal tract served as a Control group; four dogs had transection and reanastomosis of the duodenum 0.5 cm distal to the pylorus (Pyloric Transection group); and seven dogs had identical proximal duodenal transection, but with oversewing of duodenum and pylorojejunostomy to a Roux-en-Y limb (Roux-en-Y group). In the Control and Pyloric Transection groups, the gastric and intestinal MMCs were similar in appearance, the cycle durations (x +/- SEM) were not different (134 +/- 19 vs 111 +/- 26 min, respectively; P > 0.05), and the times between the start of gastric and duodenal Phase III (gastroduodenal latency) were similar (6 +/- 1 vs 10 +/- 3 min; P > 0.05). In the Roux-en-Y group, MMCs also occurred in six of seven dogs but tended to have a longer cycle duration (176 +/- 19 min) and a more variable gastroduodenal latency (23 +/- 15 min). Plasma motilin concentration, measured only in the Roux-en-Y group, was greater during Phase III in the stomach and duodenum than during Phases I or II (P < 0.05). Feeding inhibited the gastric and duodenal MMCs in all groups, but the duodenal MMC returned earlier in the Roux-en Y group. The Roux-en-Y jejunal limb exhibited a postprandial pattern in only seven of 14 studies.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1494293 TI - Effects of homodimeric isoforms of platelet-derived growth factor (PDGF-AA and PDGF-BB) on wound healing in rat. AB - Platelet-derived growth factor (PDGF) has been suggested to have a significant role in wound healing. The present work was aimed at studying the effects of PDGF AA and PDGF-BB homodimers on developing granulation tissue in rats. Subcutaneously implanted hollow cylindrical cellulose sponges were used as an inductive matrix for the ingrowth of granulation tissue. Fifty microliters of solutions containing 0, 5, 50, or 500 ng of PDGF-AA or PDGF-BB homodimers was injected daily into the sponges; 7 days after implantation the granulation tissue in the sponge cylinders was analyzed. Five hundred nanograms of PDGF-BB stimulated significantly the accumulation of collagen, indicated by the elevated hydroxyproline content of the sponge (+34%, P < 0.001). Similarly, the amounts of RNA-ribose, nitrogen, hexosamines, and uronic acids were significantly higher, reflecting a PDGF-BB-induced increase in the accumulation of RNA, protein, and glycosaminoglycans. Analyses of wound fluid showed no essential changes in the composition of different cell types after PDGF-BB-treatment. The PDGF-AA treatment increased significantly the mean amount of RNA but there were no significant changes in other parameters. In vitro both PDGF-AA and PDGF-BB increased significantly the number of rat granulation tissue derived fibroblasts in culture at concentrations of 10 and 30 ng/ml. This proliferative effect resulted in a lowered level of protein synthesis per cell. To conclude, PDGF-BB accelerates granulation tissue formation both in vitro and in vivo, whereas PDGF AA is effective in vitro but it is clearly less effective in vivo. PMID- 1494294 TI - Regulatory effects of interleukin-4 on tumor-infiltrating lymphocytes derived from human renal cell carcinoma. AB - We have studied the effects of interleukin-4 (IL-4) on the expansion, proliferation, phenotype, and antitumor activity of tumor-infiltrating lymphocytes (TIL) derived from human renal cell carcinoma. Cultures were obtained from three primary renal tumors and one group of tumor-invaded, regional lymph nodes. IL-4 induced a significant increase in lymphocyte expansion and proliferation, but the response was dependent on the concurrent dose of IL-2 in culture. Increased growth activity was only observed in those cultures receiving low doses (20 U/ml) of IL-2 (average increase of fold expansion of 6.5, P < 0.01) with no changes in growth activity in the high dose (1000 U/ml) cultures. The combination of low dose IL-2 and IL-4 (200 U/ml) promoted lymphocyte growth significantly better than high dose IL-2 alone, the current standard growth regimen for in vitro expansion of TIL. TIL grown in the presence of IL-4 significantly reduced the level of non-specific, non-major histocompatibility complex-restricted antitumor activity (P < 0.01 for allogeneic renal, nonrenal, and NK-sensitive K562 cells), while exhibiting no effect on the level of autologous killing. This is in contrast to previous findings of significant enhancement of autologous antitumor activity using IL-4 on tumor-specific, melanoma-derived TIL. We also evaluated the effects of irradiated autologous tumor stimulation (TIL:tumor ratio, 10:1) on TIL cultures. Addition of autologous tumor cells increased expansion and proliferation of all cultures regardless of concurrent lymphokines present in the culture media (average increase fold expansion of 2.21, P < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1494295 TI - Acute effects of a nucleoside analog dideoxyinosine (DDI) on the pancreas. AB - Dideoxyinosine (DDI, Videx) is a recently developed nucleoside analog with activity against the human immunodeficiency virus. A significant number of patients with AIDS or AIDS-related complex treated with DDI have developed acute pancreatitis. This study was performed to investigate the acute effects of DDI on the pancreas utilizing an isolated ex vivo perfused canine pancreas preparation. Control preparations remained normal throughout a 4-hr perfusion period. The addition of 12.5 mg of DDI to the perfusate (ca. 100 mumol/liter) did not induce any changes in the preparation. The addition of 62.5 mg of DDI to the perfusate (ca. 500 mumol/liter) did not induce changes in the gross appearance, weight gain, or amylase activity. However, the arterial pressure and the oxygen consumption of the preparation decreased significantly after the administration of DDI. The amount of zymogen in the acinar cells also decreased, as evaluated by electron microscopy. Protein secretion increased temporarily, probably as a result of acinar cell emptying (increased secretion without new synthesis). Water and bicarbonate secretion were also increased during the fourth perfusion hour. PMID- 1494296 TI - Relation between arterial hypoxemia and plasma eicosanoids in neonates with congenital diaphragmatic hernia. AB - Pulmonary hypertension is a major source of morbidity and mortality in infants born with congenital diaphragmatic hernia (CDH). Increased pulmonary vascular resistance leads to right-to-left shunting, which is evident as decreases in the PaO2 measured in postductal arterial blood. Thromboxane A2 (TXA2), a vasoconstrictor, and prostacyclin (prostaglandin I2, PGI2), a vasodilator, have been studied as possible mediators of pulmonary hypertension in certain conditions of the newborn, including congenital diaphragmatic hernia (CDH). The goal of our study was to determine the association of TXA2 and PGI2 levels with hypoxemia in infants born with CDH. Eleven newborn infants with severe respiratory insufficiency (birth weight 2.0-4.1 kg; gestational age 32-42 weeks) were studied 0-5 days after surgical repair of CDH. Umbilical artery samples were collected for arterial blood gas determinations and radioimmunoassay of thromboxane B2 (TXB2) and 6-keto prostaglandin F1 alpha (6-keto-PGF1 alpha), stable metabolites of TXA2 and PGI2, respectively. Postductal arterial hypoxemia (reflected by a low a-A ratio, the ratio of oxygen tension in arterial blood to that in the alveolus) was associated with increases in TXB2 (r = -0.71, P = 0.004) and 6-keto-PGF1 (r = -0.65, P = 0.017). The a-A ratio also correlated inversely with TXB2/6-keto-PGF1 alpha (r = -0.50, P = 0.01), suggesting an increased influence of the vasoconstrictor TXA2.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1494297 TI - Effects of splenectomy and splenic artery ligation on the portal pressure in portal hypertensive rats. AB - Immediate, short-, and long-term effects of splenectomy and splenic artery ligation on the portal pressure were studied in animal models experimentally created by partial portal vein ligation. The portal pressure of these animals would usually elevate immediately after partial ligation of the portal vein from a normal level of 6.0 +/- 0.5 to 14.8 +/- 1.3 mm Hg (P < 0.005), which could be maintained at least for 6 months. The portal pressure measured at 2 weeks, 4 weeks, and 6 months after portal vein ligation was 14.0 +/- 2.7, 15.2 +/- 2.7, and 12.7 +/- 2.0 mm Hg, respectively (P < 0.005, as compared with the normal). When splenectomy was performed on these animals at 2 weeks after partial portal vein ligation, the pressure dropped immediately but only transiently from 14.0 +/ 2.7 to 11.0 +/- 3.0 mm Hg, and bounced back to the presplenectomy level in 20 sec. After an additional 2 weeks, the portal pressure in these splenectomized rats was usually at 15.2 +/- 4.2 mm Hg, which was indistinguishable from that of rats whose portal vein was ligated but the spleen was not removed. Six months after splenectomy, however, the portal hypertensive rats had a portal pressure of 17.1 +/- 6.4 mm Hg, which was significantly higher than that of the controls. Splenic artery ligation, on the other hand, did not result in any immediate decrease in portal pressure (14.0 +/- 2.7 mm Hg vs 14.6 +/- 1.4 mm Hg; P > 0.1).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1494298 TI - Improvement of flow through arterial stenoses by drag reducing agents. AB - The potential of drag reducing polymers (DRP) to selectively improve blood flow through clinically significant arterial stenoses was investigated. An artificial stenosis of the left common iliac artery in dogs decreased left femoral artery pressure by 25%. High-molecular-weight polyacrylamide (PA) or polyethylene oxide (PEO) were infused at a slow constant rate while we measured left and right common iliac artery blood flows and left and right femoral artery and vein pressures. As DRP were infused, left iliac artery flow (QL) increased early and then decreased to baseline values as flow began to increase in the right iliac artery. The peak increase in QL was 24 +/- 9% for PA and 46 +/- 19% for PEO and occurred before right iliac artery flow (QR) increased. As additional polymer was infused, QR increased to a maximum of 41 +/- 12 and 131 +/- 40% with PA and PEO, respectively. Femoral artery pressures and hindlimb resistances tended to decrease in both limbs but the only significant differences occurred in the right (nonstenosed) side when QR was elevated. This study provides the first evidence that low concentrations of DRP might be capable of improving blood flow through stenotic blood vessels without altering flow in normal vessels. Although DRP might represent a new class of compounds that could be utilized in the treatment of cardiovascular diseases, the degree of variation in individual responses is a concern, the exact mechanism of action is unclear, and information on pharmacodynamics is lacking. PMID- 1494299 TI - Effects of intracerebroventricular endothelin-1 on CNS and cerebral hypoxia/ischemia and their modification by cinnarizine. AB - The central effects of endothelin-1 (ET-1) and their modification by the calcium entry blocker cinnarizine have been investigated using CNS and hypoxia/ischemia tests. CNS tests comprised behavior, horizontal and vertical motor activity and hot plate test. Hypoxia/ischemia tests used were hypobaric hypoxia and complete ischemia by decapitation. ET-1 was injected intracerebroventricularly (i.c.v.) in a volume of 0.01 ml at doses of 1.25, 2.5 and 5 pmol/mouse 15 min before the tests. Cinnarizine (10 mg/kg, i.p.) was administered 60 min prior to ET-1. The i.c.v. ET-1 at all the doses used decreased horizontal and vertical motor activity and produced barrel-rolling. Survival/gasping time of mice subjected to hypoxia/ischemia increased dose-dependently. ET-1 showed an antinociceptive effect. Cinnarizine attenuated the appearance of barrel-rolling, did not antagonize disturbances in motor activity and reversed the antinociceptive effect of ET-1. In hypobaric hypoxia and decapitation cinnarizine antagonized the effects of 5 pmol/mouse ET-1 and potentiated that of 1.25 pmol/mouse. The pharmacological modification of the ET-1 effects by cinnarizine strongly suggests that the CNS actions of ET-1 might be due to multiple mechanisms triggered by an increased influx of extracellular Ca2+ into the brain cells. PMID- 1494300 TI - Effect of CDP-choline on learning and memory processes in rodents. AB - The effects of cytidine (5') diphosphocholine (CDP-choline) on learning and memory were studied using conditioned reflex methods for passive avoidance and active avoidance with punishment reinforcement (step-through, step-down, shuttle box and maze), for active avoidance with alimentary reinforcement (staircase maze), and the Morris water maze. The majority of experiments involved comparative studies of the nootropic drugs meclofenoxate and/or piracetam. CDP choline was administered orally, in some of the experiments also intraperitoneally, at doses of 10-500 mg/kg body weight once or twice daily for 5 or 7 days. In separate cases only single doses were administered. Trainings started one hour after the last dose of the drugs. Retention tests were given 3 h, 24 h, 7 days or 10 days after training. The results obtained with the different methods document CDP-choline's ability to improve learning and memory in rats and mice. No essential differences in the effects of CDP-choline were established upon oral and intraperitoneal administration of the drug. The learning- and memory-facilitating effects of CDP-choline were similar to those of meclofenoxate and piracetam. The results of the present study permit us to define CDP-choline as a substance capable of improving cognitive levels. PMID- 1494302 TI - Inhibition of human brain and RBC acetylcholinesterase (AChE) by heptylphysostigmine (HPTL). AB - Heptylphysostigmine (HPTL), a derivative of the AChE inhibitor physostigmine (PHY), is under investigation as a therapeutic agent in Alzheimer's disease. HPTL is active against human RBC AChE both in vitro and in vivo. Activity of HPTL against human brain has not been documented. We have developed an in vitro assay system using particulate membrane fractions which permits comparison of inhibition and recovery kinetics of human RBC (primarily globular dimer) and brain (primarily globular tetramer) membrane-bound forms. Under these conditions the HPTLIC50 is similar for the two forms. RBC AChE inhibition spontaneously reverses in 24 h, as occurs in vivo. In striking contrast, activity of inhibited brain enzyme does not recover on overnight incubation. DDVP-induced inhibition, but not HPTL inhibition, can be reversed by the oxime 2-PAM. Some recovery of HPTL inhibition, but not to the level seen with RBC AChE, occurs on addition of heat-stable fractions from serum or CSF. Brain enzyme recovers rapidly from PHY in this system. Responses of brain and RBC AChE to HPTL indicate that these forms are functionally as well as structurally distinct. Since brain inhibition apparently does not spontaneously reverse like RBC inhibition, peripheral measurements of patient responses should be assessed with caution during treatment with HPTL. PMID- 1494301 TI - Modulation of memory retrieval by pre-testing vasopressin: involvement of a central cholinergic nicotinic mechanism. AB - Lysine vasopressin (LVP, 0.003-1.0 mcg/kg, s.c.) and the central acting nicotinic cholinergic agonist nicotine (N, 1.0-30.0 mcg/kg, s.c.) enhanced, whereas the vasopressin receptor antagonist 1-beta-mercapto-beta, beta cyclopentamethylenepropionic acid-2-(O-methyl)tyrosine, arginine vasopressin (AAVP, 0.01-0.3 mcg/kg, s.c.) impaired retention test performance on a one-trial step-through inhibitory avoidance task when injected into male Swiss mice 20 min before the retention test. Tests were done 48 h following training. In all cases, the effects on retention test performance were dose-dependent. Neither LVP, N nor AAVP when given prior to testing modified latencies to step-through of mice that had not received a footshock during training. These findings suggest that LVP, N and AAVP influence memory retrieval processes. The effect of LVP on memory retrieval was antagonized by the simultaneous administration of AAVP (0.01 mcg/kg, s.c.) or mecamilamine (5 mg/kg, s.c.), but not by hexamethonium (5 mg/kg, s.c.), atropine (0.5 mg/kg, s.c.) or methylatropine (0.5 mg/kq, s.c.). On the contrary, the effect of N was only prevented by mecamilamine (5 mg/kg, s.c.). These results suggest a modulatory role of vasopressin on the activity of central cholinergic nicotinic mechanisms which are critical for memory retrieval. PMID- 1494303 TI - Internally standardized simultaneous assay of verapamil and N-demethyl-verapamil enantiomers in human plasma by means of high performance liquid chromatography. AB - A high performance liquid chromatographic method with internal analog standardization for the simultaneous assay of the verapamil and N-demethyl verapamil enantiomers in human plasma after administration of racemic verapamil is described. The method comprises extraction from alkalinized plasma into an n hexane/2-propanol phase (95:5), separation of the optical antipodes on a chiral phase (Daicel OJ) and quantification by means of fluorescence detection. A detection limit of about 6 pmol was determined for all four enantiomers. Under routine conditions the limit of quantification (variation coefficient < 10%) was about 8 pmol for the (R)- and (S)-enantiomers. The determination method for verapamil and N-demethyl-verapamil enantiomers is not impaired by their known metabolites. The suitability of the method for clinical pharmacology studies is demonstrated with samples obtained from healthy subjects. First results of comparative kinetics studies in humans and various animal species show marked species-dependency with prevailing (R)-enantiomer levels in humans and dogs, and the opposite in rats. PMID- 1494304 TI - Comparisons of different animal skins with human skin in drug percutaneous penetration studies. AB - The in vitro penetration of theophylline, sodium diclofenac and benzoic acid through artificial cellulose membrane and eight animal skins was investigated. The intact animal skins including stratum corneum (SC) and viable epidermis were taken from frog, snake with or without scales, nude mice, Sprague-Dawley rat, porcine and human prepuce and thigh skin. The results indicated that the penetration was fastest through cellulose membrane and frog skin and slowest through human prepuce and thigh skin. The snake skin with scales slowed down the penetration rate more significantly than the scaled skin. Benzoic acid was the fastest penetrant through all animal skins. The permeable behaviors of sodium diclofenac through SC and intact skin of snake, porcine and human were compared. In porcine, sodium diclofenac penetrated through SC at a rate 33 times higher than through intact skin, but in snake and human skin, the rate through SC was only 2.2 and 1.6 times higher than through intact ones. This implies that both viable epidermis and SC were the major rate limiting barriers in drug penetration. DSC thermograms and IR spectra showed that the SC of snake, porcine and human thigh were very similar in structure and components. The study suggests that snake skin, porcine skin and human prepuce skin could replace the human skin in in vitro drug penetration experiments. PMID- 1494305 TI - Pharmacokinetics of epirubicin emulsion and solution in rabbits after intrahepato arterial and intravenous injection. AB - The study reports pharmacokinetic findings on the disposition of a formulated emulsion of epirubicin in rabbits as compared to plain epirubicin solution after intrahepato-arterial and intravenous administration. The dose of epirubicin used was 1 mg/kg body weight. Blood samples were collected at several time points up to 6 h after administration. Serum concentrations of epirubicin were measured by liquid chromatography with fluorometric detection. The area under serum concentration-time curve (AUC infinity 0) is smallest after intrahepato injection of epirubicin emulsion. This, together with the highest apparent volume of distribution (Vss) suggest a possible targetting effect. Although the mean residence times are similar, intrahepato injection of emulsion apparently has the largest clearance. Difference in bioavailability in the general circulation between the 2 routes of administration also suggests a certain degree of liver first-pass metabolism of the drug. In view of these findings, further investigation and assessment are worthwhile for future application in human subjects. PMID- 1494306 TI - [Treatment of sleeping disease caused by trypanosoma brucei gambiense with alpha difluoromethylornithine (DFMO) in a rural hospital in Zaire]. AB - The authors report the results of 32 patients with sleeping sickness due to Trypanosoma brucei gambiense treated with DFMO (DL-alpha difluoromethylornithine), an inhibitor of polyamine biosynthesis. Between those patients, there were 5 new cases, 1 reinfection, and 26 cases with a primary, a secondary resistance or a relapse. 26 cases got DFMO only per os, but six others received first DFMO for two weeks by the intravenous way, followed by three weeks of DFMO per os. The secondary effects were never very severe and never prompted a definitive discontinuation of treatment. 12 cases were followed for a period of 24 months, 16 for a period between 1 and 18 months and 4 patients died during the study (3 during treatment and one 8 months afterwards), but we don't think that DFMO was the cause of death. Out of the 12 cases followed for two years, 11 were in perfect health at the end of this period (one case can be considered as a secondary resistance to DFMO, but it could have been a reinfection as well). For the 16 cases followed for a period less than two years, we found a very fast disappearance of trypanosomes from body fluids, immediately after the beginning of treatment, and a significant amelioration of clinical signs. After this study, the authors estimate that DFMO given orally provides as good results as DFMO given in a combined therapy. But the oral way seems much easier to administer and much cheaper in rural areas.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1494307 TI - [Angkor. The mystery of the dead city and Anopheles dirus]. AB - The desertion of Angkor, which during more than five centuries was the center of a glorious civilization, has long been a matter of mystery and conjecture. The discovery of the vectorial capacity of the jungle mosquito Anopheles dirus, its epidemiological importance in the emergence and spread of multidrug resistance in Plasmodium falciparum malaria, the wiping out of large populations after transfer or deportation of non-immune Khmers into forest areas can now easily explain the desertion of Angkor. In 1431, Angkor Thom, the capital of the Khmer kingdom surrendered to the Thai conquerors. Soon afterwards, the young king left the city in search of a new capital. As a result of the population decrease large surfaces of rice fields were abandoned and reinvaded by the jungle, the typical biotope of Anopheles dirus. Severe epidemics of Plasmodium falciparum then occurred in the non-immune population with very high mortality decreasing again the number of workers and, thus, creating a vicious circle resulting in the progressive but complete desertion of Angkor. PMID- 1494308 TI - [Darrier-Ferrand's dermatofibroma on the forehead. Wide cranial-cutaneous exeresis followed by scalp plastic surgery]. AB - The authors report on a case of Darier-Ferrand's dermatofibroma on forehead. It was a very uncommon localization. They stress on the specific treatment applied: forehead cranioectomy and scalp plasty, made compulsory after several exercises and their reappearances. PMID- 1494309 TI - [Extra-pulmonary thoracic hydatid cyst (Pneumology and radiology services of the Military Hospital of Tunis)]. AB - The authors report, in a retrospective study 11 cases of thoracic extra-pulmonary hydatic cyst observed during 4 years of pneumopathology practice. They stress the rarity of this localization and the variability of the clinical data. Chest X-Ray was found no specific whereas, computed tomography led often to the right diagnosis and helped in some cases a puncture of the hydatic cyst. PMID- 1494310 TI - [Envenomation by Echis Carinatus in Africa: clinical study and evolution. Indications for antivenins]. AB - In North Cameroon, venom inoculations by Echis Carinatus are frequent and severe and thus pose a serious problem at Public Health Services. 48 bites without antivenomous serum injection have been considered in Garoua, Benoue valley North Cameroon. Without antivenomous serum light inoculations heal spontaneous by in a couple of days about 20% of the average clinical forms are evoluting insidiously to severe globulolysis. The great majority of severe inoculations lead to dreadful hemorrhagic threatening the life of patients. New borns and infants are particularly exposed, it is not advisable to inject systematically antivenomous serum. But it has to be considered as compulsory in the three following clinical situations before 11 years of age, venom inoculation often brings about fast aggravation, mainly in new borns, after 11 years and at adult age, when clinical signs are of great concern, when hemoglobinometry indicates less than 9 gr/100 ml after 48 hours of evolution in youngs and adults, but without any symptom of severity. PMID- 1494311 TI - [Prevalence of Delta hepatitis in health workers in Dakar (Senegal)]. AB - 708 hospital workers in University Teaching Hospital of Dakar were tested to HBs antigen; among them 128 were positive and tested to Delta antibody, by ELISA Abbott kit. Seven (7) men and one woman were positive. However, the positivity of Delta antibody is neither linked to sex, nor to age of subjects. 87% of the Delta antibody carriers were found among the trainees, and 50% of them studied in the Odonto-Stomatology Institute. PMID- 1494312 TI - [Epidemiology of human urban schistosomiasis in Bamako in Mali (the case of the "populous" quarter of Bankoni)]. AB - From may 1989 to january 1990, we have studied parasitologic index in snails population, stools and urines examination in children (1-15 years) in one of the greatest "spontaneous" quarter of Bamako. 584 stools samples and 563 urines were tested. 4.717 snails were captured during six months. From all these data, we conclude that in Bankoni S. haematobium is mesoendemic (36.6%) and S. mansoni hypoendemic (3.4%). B. truncatus is the most important host for urogenital schistosomiasis. The two seasonal revers (Tienkole and Bankoni) are unfavourable to B. pfeifferi's production. B. globosus and B. forskalii are not frequent in this suburban area. This investigation, shows that a selective mass treatment with praziquantel is the better public health care strategy in Bankoni quarter. PMID- 1494314 TI - [Duodenal tuberculosis: a case report]. AB - The authors relate the case of a duodenal tuberculosis shown by a pyloro-duodenal stenosis. They emphasize the absence of specific clinical, radiological endoscopic and histological manifestations. Laparotomy is in most cases necessary. The diagnosis is therefore affirmed out of the findings of peritoneal granulations or the extemporaneous anatomo-pathological investigation of lymphatic nodules. PMID- 1494313 TI - [Cryptococcosis caused by Cryptococcus neoformans var. Gattii. A case associated with acquired immunodeficiency syndrome (AIDS) in Kinshasa, Zaire]. AB - Since the introduction of AIDS, the biovar neoformans of Cryptococcus neoformans has replaced the biovar gattii as the predominant agent of cryptococcal meningitis in Kinshasa and in other tropical areas. That this is not an absolute rule is demonstrated by the present case of a HIV-positive patient, observed at the Kinshasa University Hospital, with cryptococcal meningitis due to the biovar gattii. Only four cases of this association have been published before. The authors conclude that both biovars are capable of infecting HIV-positive patients but that the apparent decline of the biovar gattii is related to the rarity of its natural reservoir in the urban environment, where the AIDS epidemic is concentrated. PMID- 1494315 TI - [Cure of an enormous eventration by abdominoplasty. Technical note. A case report]. AB - The secondary eventrations after delivery are the prime cause of women's eventrations. These eventrations are enormous in Africa because the post-partum women do not make active movements to develop again the abdominal strap. In Europa or North America the treatment would make use of prosthetic materials but in Africa the climatic and working conditions do not take the utilization of such method. The authors purpose a cure allied aponevroplasty according to JUDD technique with abdominoplasty. The result is satisfactory and durable. PMID- 1494317 TI - Is chronic low self-esteem the cause of eating disorders? AB - Low self-esteem occurs commonly in patients with an eating disorder, a term which includes patients with both anorexia nervosa and bulimia nervosa. In this hypothesis it is proposed that chronic low self-esteem is a necessary prerequisite to the development of an eating disorder, and that chronic low self esteem is the final common pathway through which the multiple aetiological factors involved in the causation of eating disorders act. Thus, eating disorders can best be viewed as a 'symptom' of chronic low self-esteem. This hypothesis is able to account for the recent increase in the incidence of eating disorders, and the increased incidence of depression in eating disordered patients. Suggestions for research to test this hypothesis are made. PMID- 1494316 TI - [Bacteremia caused by non-typhoid Salmonellas during an infection by the human immunodeficiency virus (HIV) in the African adult]. AB - Infection caused by non-typhous Salmonellae during the course of HIV infection is known since 1983. The authors report on 103 bacteremiae of this type found in one year. Diagnosis has been based on hemocultures. 86 patients out of 103 were HIV+. All of them were febrile. 67 suffered from digestive disorders, 33 with diarrhoea. Splenomegalia was noted in 16 cases and consciousness troubles in 13 cases. At the admission, 8 complications were observed. Other infections were associated in 86 cases particularly in HIV+ patients evolutive tuberculosis (38 cases), candidosis of oropharynx (32 cases), neuromeningeal crytococcosis (13 cases), pneumocystosis (3 cases), Kaposi's sarcoma was discovered in 3 cases. The salmonellae isolated were in the 54 cases where characterization was made: Salmonella typhi murium in 44 cases and Salmonella enteridis in 10 cases. Classical cure (chloramphenicol) was effective in 85% of the treated patients. 28 positive hemocultures out of 103 isolated non-typhous Salmonellae were sampled later than the 72th hour after admission. This fact poses the problem of nosocomial infections in hospital departments in Black Africa, where HIV+ patients represent 52% of the admissions. Non-typhous Salmonellae would be part of the definition of African AIDS concerning patients with HIV test positive. PMID- 1494318 TI - Extra-pyramidal symptoms in Alzheimer's disease: a hypothesis. AB - Recent studies have shown that compensatory processes have an important role in counteracting the neurodegenerative changes underlining Alzheimer's disease (AD), much like their well known role in Parkinson's disease (PD). In the light of these reports, we review the findings of the positive correlation existing between the appearance of extra-pyramidal symptoms and an increased rate of progression in AD patients. We propose that this correlated symptomatology arises from the wasting of globally shared compensatory resources, manifested both in an increasing inability to compensate for persisting sub-clinical nigral lesions, and in enhanced AD deterioration rate. Our hypothesis gains support from various clinical reports and by the neural modeling of synaptic changes in AD. PMID- 1494319 TI - A localized absence of interleukin-4 triggers periodontal disease activity: a novel hypothesis. AB - Pathogenic bacteria constitute the primary extrinsic agent in the etiology of Adult periodontitis. In addition to direct toxic effects, bacteria induce destructive immunologic and other inflammatory reactions in the host, leading to the observed pathologic alteration in the tissue. The risk to develop periodontal disease is not equal for all individuals, suggesting host factors are important in determining an individuals disease susceptibility. Regulation of immune response is important in maintaining the equilibrium between periodontal health and disease. We hypothesize that, in the case of Adult periodontitis, a localized lack of the regulatory cytokine interleukin-4 (IL-4) in the gingival tissues predisposes susceptible individuals to progress from gingivitis to periodontitis. PMID- 1494320 TI - Metabolism of the malignant cell, in vivo, is anaerobic and significantly plays a factor in the pathway to carcinogenesis. AB - The malignant cell, in vivo, metabolizes and respires anaerobically. For a good many years scientists have been aware of anaerobia being present in malignant growths. The prevailing opinion is that the malignant cell is able to remain viable in an anaerobic medium. This assumption is incorrect and is actually misleading. My investigative studies indicates that the malignant cell metabolizes and respires intracellularly so that the consequence of such a physiology is anaerobic and the basis for such anaerobia is a metabolic phenomenon. There is a reason for this anaerobiosis. Studies demonstrated the fact that there are present within the malignant cell and in the immediate area bacterial spores arising from one of several varieties of plant bacteria. And with an adequate circulating flow of blood, by the animal (human) host, to that particular site, provides the metabolites, enzymes, and the exchange of gases to enhance this abnormal physiopathological anaerobiosis. It is this intracellular anaerobic metabolism within an animal cell that becomes the basis for its malignant transformation. PMID- 1494321 TI - Risk factors for coronary heart disease: synthesis of a new hypothesis through adaptation. AB - A risk factor is a characteristic which is associated with a greater than average probability of developing coronary disease. Raised serum cholesterol and hypertension are two such factors. Intervention studies conducted to confirm the risk factor hypothesis have shown that reduction of serum cholesterol and essential hypertension may be associated with a small decreased CHD incidence, however there were almost as many deaths due to coronary disease in the intervention groups as in the control groups. These findings suggest that our approach to risk factor intervention may be a misguided attempt which needs modification. It is possible that the major risk factors develop in an attempt of our body to adapt to environmental factors such as increased intake of salt, saturated fat and cholesterol, physical inactivity, increased intake of calories and obesity and stress. Smoking may be the result of social changes. Since the body has to modify its metabolic mechanism depending upon the factor to which it adapts, development of hyperlipidemia and hypertension may be protective mechanisms of the body which it has developed while fighting against environmental factors. Reduction of major risk factors by drug therapy may mean that we are trying to prevent the body, fighting environmental factors. Thus our approach to control of the major risk factors should be to treat the causative environmental factors or alter the lifestyle.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1494322 TI - Ginger (Zingiber officinale) in rheumatism and musculoskeletal disorders. AB - One of the features of inflammation is increased oxygenation of arachidonic acid which is metabolized by two enzymic pathways--the cyclooxygenase (CO) and the 5 lipoxygenase (5-LO)--leading to the production of prostaglandins and leukotrienes respectively. Amongst the CO products, PGE2 and amongst the 5-LO products, LTB4 are considered important mediators of inflammation. More than 200 potential drugs ranging from non-steroidal anti-inflammatory drugs, corticosteroids, gold salts, disease modifying anti-rheumatic drugs, methotrexate, cyclosporine are being tested. None of the drugs has been found safe; all are known to produce from mild to serious side-effects. Ginger is described in Ayurvedic and Tibb systems of medicine to be useful in inflammation and rheumatism. In all 56 patients (28 with rheumatoid arthritis, 18 with osteoarthritis and 10 with muscular discomfort) used powdered ginger against their afflictions. Amongst the arthritis patients more than three-quarters experienced, to varying degrees, relief in pain and swelling. All the patients with muscular discomfort experienced relief in pain. None of the patients reported adverse effects during the period of ginger consumption which ranged from 3 months to 2.5 years. It is suggested that at least one of the mechanisms by which ginger shows its ameliorative effects could be related to inhibition of prostaglandin and leukotriene biosynthesis, i.e. it works as a dual inhibitor of eicosanoid biosynthesis. PMID- 1494323 TI - Cytokines play a central role in the pathogenesis of systemic lupus erythematosus. AB - Excessive production of pathogenic autoantibodies is one of the hallmarks of systemic lupus erythematosus (SLE). The mechanisms that underlie this excessive production are still unclear. Although there is considerable evidence to suggest that both T cells and B cells play an important role in the etiology of SLE, convincing abnormalities at the T cell receptor or immunoglobulin gene loci have not been demonstrated. In this regard, because cytokines play such a pivotal role in the inflammatory response, a defect in the immunoregulation of B cells by cytokines should be considered as possible contender in disease etiology. The hypothesis that is proposed here is that multiple defects mediated by cytokines are present in individuals with lupus and that both cytokine production and the response of B cells to cytokines may be defective. These abnormalities could then be a central factor in the etiology of systemic lupus erythematosus. PMID- 1494325 TI - The detachment cascade during metastasis. AB - The cause of detachment of tumour cells during metastasis is still one of the most intriguing questions of tumour propagation. A hypothesis is suggested herein for lysis of extracellular matrix that could ultimately lead to the detachment and spreading of malignant cells. According to this theory a certain optimal estrogen level initiates a series of enzymatic activations that culminate in detachment and spreading of tumour cells. PMID- 1494324 TI - Evidence for Randall's plaques to be the origin of primary renal stones. AB - Lithofibrin, a non-protein organic component of renal calculi was found in renal papillas with the aid of stereo microscopy under UV illumination. Scanning electron microscopy revealed fibers of which one had a clump containing calcium on the top. The findings support the theory of Randall, that the origin of primary renal calculi is to be found in the kidney, not in the urine. PMID- 1494326 TI - Helicobacter (aka Campylobacter) pylori as the major causal factor in chronic hypochlorhydria. AB - Helicobacter (formerly known as Campylobacter) pylori, a recently discovered gastrointestinal bacterial pathogen, has been shown to be etiologic for Type B or antral gastritis, and usually has chronic active pathological changes associated with its presence. Acute Helicobacter infection in most cases induces reduced stomach acid secretion which usually returns to normal levels of secretion after a few months. Yet Helicobacter gastritis has never been known to spontaneously remit after it has been established, and there is evidence suggesting that it often progresses to cause atrophic changes in the gastric mucosa. Since chronic gastritis has been shown in past studies to lead to chronic persistent hypochlorhydria from atrophic damage to secretory tissue, and Helicobacter has been shown to cause most chronic gastritis, the reasonable conclusion is that Helicobacter infection is etiologic for most chronic persistent hypochlorhydria. The apparent exception of the hyperchlorhydria in duodenal ulcer disease associated with Helicobacter infection is explained. The possible clinical relevance of hypochlorhydria will be the subject of a subsequent paper. PMID- 1494327 TI - The clinical importance of hypochlorhydria (a consequence of chronic Helicobacter infection): its possible etiological role in mineral and amino acid malabsorption, depression, and other syndromes. AB - In a previous paper evidence was presented to show that Helicobacter-induced chronic gastritis is the probable cause of most chronic hypochlorhydria. In this article evidence is presented for the clinical relevance of reduced stomach acid secretion. Reduced mineral absorption is fairly well documented and has sound theoretical support from basic chemistry. Impaired digestion of protein has been suggested by a few studies. Small intestinal bacterial overgrowth in hypochlorhydria probably leads to putrefactive breakdown of the metobolically useful products of protein digestion, thereby reducing their availability for certain essential pathways. The possible lowering of tryptophan, tyrosine, and phenylalanine in the blood may be a precipitating factor in depression in hypochlorhydric patients. In reduced or absent stomach acid secretion a constellation of gastrointestinal symptoms has been consistently observed and reported by clinicians in the past, and treatment of the hypochlorhydria with hydrochloric acid or its substitutes has often been observed to be effective in reducing these symptoms. PMID- 1494328 TI - Therapeutic gain with hyperfractionation in prophylactic cranial irradiation of children with acute lymphoblastic leukemia. AB - IQ deterioration after prophylactic cranial irradiation is a dreaded complication for children with acute lymphoblastic leukemia. Alternate treatment schemes are needed that achieve comparable tumor control, but avoid such long-term complication. To this end, a hyperfractionated treatment scheme is proposed. Using two different radiobiological models, we analyze the doses required to achieve equivalent disease control while reducing the severity of late sequelae. Analysis based on the linear-quadratic and surviving fractions models clearly indicates a therapeutic gain with hyperfractionation. PMID- 1494329 TI - Evaluation of suppression of growth hormone levels following a 75g oral glucose tolerance test. AB - Growth hormone (GH) levels were measured after a 75g oral glucose load (OGTT) in normal adults, patients with impaired glucose tolerance (IGT), insulin-dependent diabetes mellitus (IDDM) and acromegaly. Nadir GH levels at 2-hour post-OGTT in normal subjects ranged from 0.4 to 8.4 mIU/L, the 95% confidence interval being 0.4-4.4 mIU/L. In IGT and IDDM subjects basal fasting GH levels were not significantly different from normal and did not alter during OGTT. The high fasting GH level measured in one each of the IGT and IDDM patients was suppressible at 1-hour after glucose intake. In contrast, acromegalic patients had elevated fasting GH levels (11.8-178 mIU/L) although in 3 patients, the levels were mildly elevated and overlapped with normal. OGTT failed or only partially suppressed GH secretion in all acromegalics. Therefore, elevated fasting GH levels are not diagnostic and OGTT is required for accurate diagnosis and assessment of treatment of acromegalic patients. PMID- 1494330 TI - Breakpoint cluster region (BCR) gene rearrangement studies in chronic myeloid and acute lymphoblastic leukemias. AB - Deoxyribonucleic acid (DNA) of twenty chronic myeloid leukemia (CML) and thirty acute lymphoblastic leukemia (ALL) patients were analysed by Southern hybridization. The DNA was digested with BglII and hybridized with a 4.5-kilobase (kb) ph1/bcr-3 DNA probe. All the 20 CML patients showed gene rearrangement within a 5.8-kb segment (the major breakpoint cluster region, M-bcr) of the breakpoint cluster region (bcr) gene of chromosome 22, indicating the presence of the Philadelphia chromosome. M-bcr rearrangement at the bcr gene of chromosome twenty-two was not detected in all the thirty ALL patients (nine adults and twenty-one children) and two normal controls. PMID- 1494331 TI - The clinical significance of the branching pattern of the facial nerve in Malaysian subjects. AB - Fine dissection was carried out in 79 facial halves from formalin fixed Malaysian adult cadavers of various races, to trace the extracranial part of the facial nerve and its peripheral branches. The facial nerve trunk, after leaving the stylomastoid foramen was located at a depth of 1 to 2 cm from the skin in the vagino-mastoid angle. It bifurcates at the posterior border of the ramus of the mandible and in 3.8% trifurcation was found. Mean distance of bifurcation from the angle of the mandible was 28.06 mm and 81.0% were within the range of 21 to 35 mm. The branching patterns were classified into six types, and the frequency of occurrence was type I 11.39%, type II 15.9%, type III 34.18%, type IV 18.98%, type V 7.59% and type VI 12.67%. Type I, a classical text book pattern was found to be one of the least common patterns. There is no significant difference in percentage of each type between the present study and that of Koreans, though some differences with Caucasians were noted in three uncommon types. The frontal branch could be outlined between the two diverging lines from the earlobe to the lateral ends of the eyebrow and the highest frontal crease. Posterior to the facial artery, the mandibular branch was seen passing below the inferior border of the mandible in 20%; anterior to the artery, this nerve divides into one to four branches. In almost all the cases, branches to the mentalis and the depressor labii inferioris muscles and infrequently branches to the depressor angular oris were seen below the inferior border of the mandible.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1494332 TI - A report of the first 20 cases using a simple external fixator. AB - The results of treatment using a locally-designed external fixator in 20 patients are presented. Open fractures were the main indications for external fixation. Pin tract infection occurred in 8 patients. Only 2 patients had unstable fixation which required removal of the device. One third of patients developed malunion exceeding 15 degrees and two thirds had joint stiffness after conversion to plaster cast. This external fixator is adequate in the treatment of most open fractures of the tibia. However, improved techniques of pin insertion and cast application upon removal of the external fixator may help to reduce the incidence of pin tract infections and malunion. PMID- 1494333 TI - Oral pefloxacin in the treatment of CAPD peritonitis. AB - Continuous ambulatory peritoneal dialysis (CAPD), a widely used replacement therapy for end stage renal failure, is frequently complicated by bacterial peritonitis. The infecting organisms are mainly staphylococci and gram negative aerobes. Pefloxacin is a fluorinated quinolone with good in-vitro activity against these pathogens. The objective of this open non comparative study is to determine the effectiveness and safety of oral pefloxacin mesylate as a single first line antimicrobial treatment of CAPD peritonitis. 28 episodes of CAPD peritonitis were treated with a stat dose of pefloxacin 800 mg. followed by 400 mg. 12 hourly for about 15-18 days. A pefloxacin sensitive organism was isolated in 17 episodes. 11 episodes were culture negative. Treatment results showed a cure in seventeen (60.7%), no treatment response in seven (25%), and relapses in four (14.2%). Side effects encountered were not serious except for one incident of a generalized seizure. We conclude that oral pefloxacin is convenient, safe and effective enough as a single first line antimicrobial treatment for CAPD peritonitis. PMID- 1494334 TI - A survey of breast feeding practices in infants seen in general practice. AB - This is a study of infant feeding practices of 126 mothers. Seventy-seven mothers or 61.1% practised breast feeding. The typical breast feeding mother was more likely to be a Malay, with lower family income and residing in the rural area. The educational status of the mother was not an important factor in influencing her to breast feed. Health education on breast feeding should be intensified in schools to reinforce the implementation of the Malaysian Code of Ethics for Infant Formula Products. PMID- 1494335 TI - Malignant lymphoma of nasal septum--a case report. AB - Malignant lymphoma of nasal septum is uncommon. It presents a problem in diagnosis to both otorhinolaryngologist and pathologist. This case report is about one such patient in whom the local disease has been controlled with the treatment of radiotherapy alone. However it is suggested that combined treatment of radiotherapy and cytotoxic therapy might improve the survival rate. PMID- 1494336 TI - The clinical use of leucocyte--depleting filters in the multiply transfused patients--a case report. PMID- 1494337 TI - Acute appendicitis presenting as melaena. PMID- 1494338 TI - Role of PORIM in nutritional research. PMID- 1494339 TI - An appraisal of the nutritional and health aspects of palm oil. PMID- 1494340 TI - Thalassaemia and haemoglobinopathies in Brunei Darussalam. AB - One thousand consecutive Brunei Darussalam patients referred with low Hb, and/or low MCV and MCH (Hb < 12.5g/dl, MCV < 76fl, MCH < 27pg) were studied in the laboratory for underlying haemoglobinopathies. 30.0% of such patients were proved to have either beta-thalassaemia trait, beta-thalassaemia major, Hb AE, Hb EE, Hb E beta-thalassaemia or Hb H disease. In some, the haemoglobin abnormality was not identified precisely. Alpha-thalassaemia was suspected in an additional 4.3% of cases but confirmation study by globin-chain synthesis was not available. Beta thalassaemia trait which was the predominant disorder was equally distributed among the three major race groups of Brunei Darussalam. Hb E was found exclusive among the Malay population. Hb H disease appeared as more common among the Chinese or the Malays (p > 0.05). This study reveals that thalassaemia and haemoglobinopathies are prevalent in Brunei Darussalam. PMID- 1494341 TI - Design of a novel system for the construction of vectors for Agrobacterium mediated plant transformation. AB - The loxP-Cre site-specific recombination system of phage P1 was used to develop a novel strategy to construct cointegrate vectors for Agrobacterium-mediated plant transformation. A pTi disarmed helper plasmid (pAL1166) was constructed by replacing the oncogenic T-DNA by a loxP sequence and a spectinomycin resistance marker in the octopine-type pTiB6 plasmid. The cre gene was cloned into an unstable incP plasmid. A third plasmid, which did not replicate in Agrobacterium and contained another loxP sequence together with a kanamycin resistance marker, was used to test the system. Electroporation of this third plasmid into an Agrobacterium strain harbouring both pAL1166 and the Cre-encoding plasmid resulted in kanamycin-resistant cells containing a cointegrate between pAL1166 and the incoming plasmid. Cointegration occurred by Cre-mediated recombination at the loxP sites, and the cointegrate was stabilized in the Agrobacterium cells by the loss of the Cre-encoding plasmid shortly after the recombination event had taken place. PMID- 1494342 TI - A dominant selectable marker that is meiotically stable in Neurospora crassa: the amdS gene of Aspergillus nidulans. AB - When Neurospora crassa is transformed using a Neurospora gene as the selectable marker, the vegetatively stable transformants obtained cannot be used successfully in a cross because the selectable marker will be inactivated by the process of RIP (repeat-induced point mutation). Introduction of the acetamidase encoding gene amdS of Aspergillus nidulans into N. crassa by transformation yielded transformants that would grow in minimal medium containing acetamide as a sole nitrogen source. In mitotically stable transformants containing a single copy of the amdS gene, the capacity to utilize acetamide as a sole nitrogen source was maintained in the progeny of a sexual cross. Therefore, the A. nidulans amdS gene is an appropriate dominant selectable marker for use in transformation analyses with N. crassa in which sexual crosses will be subsequently performed. PMID- 1494344 TI - Cloning, nucleotide sequence and characterization of the gene encoding the Erwinia chrysanthemi B374 PrtA metalloprotease: a third metalloprotease secreted via a C-terminal secretion signal. AB - Erwinia chrysanthemi, a phytopathogenic enterobacterium, secretes three proteases (PrtA, PrtB and PrtC) into the extracellular medium. The gene encoding the 50 kDa protease, prtA, was subcloned from a recombinant cosmid carrying a fragment of the E. chrysanthemi B374 chromosome. prtA was shown to be located immediately 3' to the structural genes for the other two extracellular proteases. The amino acid sequence of PrtA, as predicted from the prtA nucleotide sequence, showed a high level of homology with a family of metalloproteases that are all secreted via a signal peptide-independent pathway, including PrtB and PrtC of E. chrysanthemi B374, PrtC of E. chrysanthemi EC16, PrtSM of Serratia marcescens and AprA of Pseudomonas aeruginosa. PrtA secretion requires the E. chrysanthemi protease secretion factors PrtD, PrtE and PrtF. The secretion signal of PrtA is near to the carboxy-terminal end of the protein, as was previously shown to be the case for PrtB and PrtSM and for Escherichia coli alpha-hemolysin. The C-termini of these four proteins do not show extensive primary sequence homology, but PrtA, PrtB and PrtSM each have a potential amphipathic alpha-helix located close to the C-terminus. PMID- 1494343 TI - Nucleotide sequence analysis and comparison of the lexA genes from Salmonella typhimurium, Erwinia carotovora, Pseudomonas aeruginosa and Pseudomonas putida. AB - The complete nucleotide sequences of the lexA genes from Salmonella typhimurium, Erwinia carotovora, Pseudomonas aeruginosa and Pseudomonas putida were determined; the DNA sequences of the lexA genes from these bacteria were 86%, 76%, 61% and 59% similar, respectively, to the Escherichia coli K12 gene. The predicted amino acid sequences of the S. typhimurium, E. carotovora and P. putida LexA proteins are 202 residues long whereas that of P. aeruginosa is 204. Two putative LexA repressor binding sites were localized upstream of each of the heterologous genes, the distance between them being 5 bp in S. typhimurium and E. carotovora, as in the lexA gene of E. coli, and 3 bp in P. putida and P. aeruginosa. The first lexA site present in the lexA operator of all five bacteria is very well conserved. However, the second lexA box is considerably more variable. The Ala-84--Gly-85 bond, at which the LexA repressor of E. coli is cleaved during the induction of the SOS response, is also found in the LexA proteins of S. typhimurium and E. carotovora. Likewise, the amino acids Ser-119 and Lys-156 are present in all of these three LexA repressors. These residues also exist in the LexA proteins of P. putida and P. aeruginosa, but they are displaced by 4 and 6 residues, respectively. Furthermore, the structure and sequence of the DNA-binding domain of the LexA repressor of E. coli are highly conserved in the S. typhimurium, E. carotovora, P. aeruginosa and P. putida LexA proteins. PMID- 1494345 TI - STE50, a novel gene required for activation of conjugation at an early step in mating in Saccharomyces cerevisiae. AB - A new gene, STE50, which plays an essential role in cell differentiation in Saccharomyces cerevisiae was detected and analysed. STE50 expression is not cell type-specific and its expression in MATa and MAT alpha cells is unaffected by pheromones. When present on a high copy number plasmid, STE50 causes supersensitivity to alpha-pheromone, and increases the level of alpha-pheromone induced transcription of FUS1 in haploid a cells. Mutants bearing either of the two gene disruptions, ste50-1 or ste50-2, are sterile and have a modulated sensitivity to alpha-pheromone. The overexpression of STE4 (G beta) in wild-type cells elicits a constitutive growth arrest signal, however this phenotype is suppressed by a C-terminal truncation mutation in STE50 (ste50-2). In contrast, the constitutive activation of the pheromone response pathway caused by disruption of GPA1 (G alpha) is not suppressed in ste50-2 mutants. The ste50-2 mutation partially suppresses the desensitisation defect of the sst2-1 mutation, and the resulting ste50-2 sst2-1 mutants restore fertility. Our results indicate that the ste50-2 mutant may have a defect in adaptation (hyperadaptation), and suggest a possible interaction of STE50-2 with the G alpha subunit of the G protein. PMID- 1494346 TI - The REV3 gene of Saccharomyces cerevisiae is transcriptionally regulated more like a repair gene than one encoding a DNA polymerase. AB - We measured the relative steady-state levels of the mRNA transcribed from the Saccharomyces cerevisiae REV3 gene in cells at different stages of the mitotic and meiotic cycles, and after UV irradiation. This gene is thought to encode a DNA polymerase concerned only with a specific recovery function, the replication on mutagen-damaged templates that produces damaged-induced mutations. In keeping with this proposed function, the REV3 gene showed no evidence of the periodic transcription at the G1/S boundary of the mitotic and meiotic cycle that occurs with genes encoding replication enzymes. However, levels of REV3 mRNA were much increased in late meiotic cells, like those of transcripts of some other DNA repair-related genes. Steady-state levels of REV3 transcript were increased only slightly in response to UV irradiation. PMID- 1494347 TI - Regulatory elements for expression of the alkA gene in response to alkylating agents. AB - Expression of the alkA gene in Escherichia coli is controlled by Ada protein, which binds to a specific region of the alkA promoter and enhances further binding of RNA polymerase holoenzyme to the complex. To determine the sequence recognized by the Ada protein, we introduced various base substitutions into the promoter region of alkA and examined their effects on expression of the gene, both in vivo and in vitro. Base changes within the sequence AAAGCAAA, located between positions -41 and -34 from the transcription initiation site, greatly decreased the frequencies of initiation of transcription. In footprinting experiments, the region containing this sequence was protected by the Ada protein and base changes within this sequence led to failure of binding of Ada protein to the promoter. It is likely that the Ada protein recognizes the AAAGCAAA sequence in the alkA promoter and binds to the region containing the sequence, thereby allowing ready access of RNA polymerase to the promoter. There are considerable differences between the mechanisms of action of Ada protein on the promoters of alkA and ada, even though the expression of both genes is positively regulated by Ada protein. PMID- 1494348 TI - The nad4L gene is encoded between exon c of nad5 and orf25 in the Arabidopsis mitochondrial genome. AB - In the Arabidopsis thaliana mitochondrial genome the gene coding for subunit 4L of NADH dehydrogenase (nad4L) is located between exon c of the nad5 open reading frame and orf25. The physical proximity of these genes further supports the trans splicing model for assembly of the nad5 mRNA. Some transcripts comprise the nad4L open reading frame cotranscribed with nad5 exon c and orf25, while other mRNAs contain only nad4L and orf25. Both open reading frames for nad4L and orf25 are edited in several positions with different frequencies. PMID- 1494349 TI - Organization and nature of fortimicin A (astromicin) biosynthetic genes studied using a cosmid library of Micromonospora olivasterospora DNA. AB - The cloning of five DNA segments carrying at least seven genes (fms1, fms3, fms4, fms5, fms7, fms11, and fms12) that participate in fortimicin A (astromicin) biosynthesis was described previously. These DNA fragments were used to screen a cosmid library of genomic DNA in order to examine if these biosynthetic genes are clustered in Micromonospora olivasterospora. One cosmid clone (pGLM990) was obtained, which hybridized to all the probes. Complementation analysis, using mutants blocked at various steps and chimeric plasmids subcloned from pGLM990, showed that three additional genes (fms8, fms10, and fms13) are present in pGLM990. A gene conferring self-resistance to the antibiotic, which was independently cloned in Streptomyces lividans, using the plasmid vector pIJ702 was also found to be linked to the cluster of biosynthetic genes. Thus, at least ten biosynthetic genes and a self-defense gene are clustered in a chromosomal region of about 27 kb in M. olivasterospora. Interestingly, the fms8 gene which participates in the dehydroxylation step of fortimicin A biosynthesis was found to have homology with a neomycin resistance gene nmrA from the neomycin-producing Micromonospora sp. MK50. Studies using a cell-free extract of the fms8 mutant and its parent strain showed that the enzyme encoded by fms8 phosphorylates a biosynthetic precursor, fortimicin KK1, in the presence of ATP. Thus the dehydroxylation reaction is suggested to occur via the phosphorylation of the target hydroxyl group. DNA regions homologous to fms genes were found in Micromonospora sp. SF-2098 and Dactylosporangium matsuzakiense, both producers of fortimicin group antibiotics. PMID- 1494350 TI - N-formimidoyl fortimicin A synthase, a unique oxidase involved in fortimicin A biosynthesis: purification, characterization and gene cloning. AB - Micromonospora olivasterospora, a fortimicin A (FTM A, astromicin) producer, was found to carry an enzyme that converts FTM A to N-formimidoyl FTM A (FI-FTM A). This enzyme (FI-FTMase) was purified to homogeneity and shown to be a flavin adenine dinucleotide (FAD) enzyme. Tracer experiments proved that the formimidoyl group was derived from C-2 of glycine via oxidation of the amino acid in the presence of FTM A and oxygen. The gene encoding this enzyme, fms 14, was cloned using a 26-mer oligonucleotide probe, designed according to the N-terminal amino acid sequence of purified FI-FTMase, from a cosmid clone pGLM990, which has been shown to contain a cluster of FTM A biosynthetic genes. The nucleotide sequence, and biochemical and genetic analysis revealed that FI-FTMase is composed of four identical subunits of mol. wt. 52,000, and contains at least one FAD per subunit. DNA regions homologous to fms14 were found in two other producers of the fortimicin group of antibiotics, Dactylosporangium matsuzakiense ATCC31570 and Micromonospora sp. SF-2098. PMID- 1494351 TI - Intramolecular homologous recombination in Bacillus subtilis 168. AB - Plasmid resolution from a phage::plasmid chimera was used to measure directly intramolecular recombination in Bacillus subtilis. The system is based on a sigma replicating plasmid (pC194) cloned into a dispensable region of the lytic bacteriophage SPP1. The plasmid, which confers chloramphenicol resistance, is resolved when SPP1::pC194 phages infect B. subtilis cells, provided the chimera carries a functional, intact copy of the plasmid repH gene. Intramolecular homologous recombination was independent of the RecA and RecL-RecR functions, but dependent on RecF, RecB, RecG, RecP, RecH and AddAB functions. These results are consistent with the hypothesis that B. subtilis has multiple pathways for genetic recombination and allow us to tentatively place the recB and recG genes into a new epistatic group epsilon. PMID- 1494352 TI - Downstream activating sequence within the coding region of a yeast gene: specific binding in vitro of RAP1 protein. AB - Using a gel retardation assay, a protein factor that specifically interacts with a 33 bp intragenic sequence of the highly expressed and glucose-inducible SRP1 gene of Saccharomyces cerevisiae has been detected. This binding site is located in a transcribed region and within the open reading frame (positions +710 to +743 relative to the first base of the initiation codon). A mutant strain carrying a deletion of this binding site showed a dramatic decrease in steady-state levels of SRP1 transcripts. This decline is not the result of a decrease in mRNA stability, since expression of hybrid genes in which the SRP1 promoter was replaced by the heterologous CYC1 promoter was not affected by the binding site deletion. These findings suggest that the 33 bp sequence contains a cis-acting downstream activating element which is involved in the transcriptional activation of the SRP1 promoter. Sequence comparisons showed similarities between a site located within the 33 bp sequence and the high-affinity consensus binding site of the RAP1/GRF1 (also named TUF) factor and methylation interference experiments confirmed that this site was involved in the protein-DNA interaction. Both the results of competition experiments with upstream activating sequences of ribosomal protein genes (UASrpg), which are targets for RAP1 binding, and determination of the apparent molecular weight of the affinity-purified DNA binding protein indicated that RAP1 factor recognized the SRP1 33 bp element. The 33 bp sequence was found to be unable to provide UAS activity when placed upstream of the TATA box and transcription start site. PMID- 1494353 TI - Cloning and DNA sequence analysis of the mercury resistance genes of Streptomyces lividans. AB - A broad-spectrum mercury resistance locus (mer) from a spontaneous chloramphenicol-sensitive (Cms), arginine auxotrophic (Arg-) mutant of Streptomyces lividans 1326 was isolated on a 6 kb DNA fragment by shotgun cloning into the mercury-sensitive derivative S. lividans TK64 using the vector pIJ702. The mer genes form part of a very large amplifiable DNA sequence present in S. lividans 1326. This element was amplified to about 20 copies per chromosome in the Cms Arg- mutant and was missing from strains like S. lividans TK64, cured for the plasmid SLP3. DNA sequence analysis of a 5 kb region encompassing the whole region required for broad-spectrum mercury resistance revealed six open reading frames (ORFs) transcribed in opposite directions from a common intercistronic region. The protein sequences predicted from the two ORFs transcribed in one direction showed a high degree of similarity to mercuric reductase and organomercurial lyase from other gram-negative and gram-positive sources. Few, if any, similarities were found between the predicted polypeptide sequences of the other four ORFs and other known proteins. PMID- 1494356 TI - Antagonisms of potential concern in the clinical use of antifungal imidazoles and related azole-type drugs. PMID- 1494354 TI - Differential repair and recombination of psoralen damaged plasmid DNA in Saccharomyces cerevisiae. AB - Psoralen photoreaction with DNA produces interstrand crosslinks, which require the activity of excision and recombinational pathways for repair. Yeast replicating plasmids, carrying the HIS3, TRP1, and URA3 genes, were photoreacted with psoralen in vitro and transfected into Saccharomyces cerevisiae cells. Repair was assayed as the relative transformation efficiency. A recombination deficient rad52 strain was the least efficient in the repair of psoralen-damaged plasmids; excision repair-deficient rad1 and rad3 strains had repair efficiencies intermediate between those of rad52 and RAD cells. The level of repair also depended on the conditions of transformant selection; repair was more efficient in medium lacking tryptophan than in medium from which either histidine or uracil was omitted. The plasmid repair differential between these selective media was greatest in rad1 cells, and depended on RAD52. Plasmid-chromosome recombination was stimulated by psoralen damage, and required RAD52 function. Chromosome to plasmid gene conversion was seen most frequently at the HIS3 locus. In RAD and rad3 cells, the majority of the conversions were associated with plasmid integration, while in rad1 cells most were non-crossover events. Plasmid to chromosome gene conversion was observed most frequently at the TRP1 locus, and was accompanied by plasmid loss. PMID- 1494355 TI - NADPH: protochlorophyllide oxidoreductases in white pine (Pinus strobus) and loblolly pine (P. taeda). Evidence for light and developmental regulation of expression and conservation in gene organization and protein structure between angiosperms and gymnosperms. AB - NADPH: protochlorophyllide oxidoreductase (pchlide reductase, EC 1.6.99.1) catalyzes the light-dependent reduction of protochlorophyllide in higher plants. Cloned cDNAs encoding two distinct pchlide reductases were isolated from a lambda gt11 library constructed from poly(A)+ RNA prepared from the cotyledons of dark grown white pine (Pinus strobus) seedlings and a nuclear gene (lpcr) analogous to one of these cDNAs has been characterized from loblolly pine (P. taeda). The pine gene encodes an approximately 43 kDa precursor polypeptide consisting of a 334 amino acid mature protein and a 66-amino acid transit peptide. The deduced primary structures for the pine proteins are highly homologous to those reported from monocots and dicots. The coding portion of the pine lpcr gene is interrupted by four introns. The placement of these introns within the pine lpcr gene is identical to that observed in pea (Pisum sativum), suggesting conservation in gene organization between dicot and gymnosperm species. Western blot analysis using polyclonal antiserum against oat pchlide reductase detected in extracts of dark-grown pine cotyledons a single immunoreactive protein, which declined in abundance during a 48 h period of illumination with white light. Cotyledons of dark-grown seedlings were also found to accumulate high levels of pchlide reductase mRNA; however, little or no change in the steady-state levels of mRNA encoding pchlide reductase was observed in these tissues following illumination. Stem tissue of dark-grown seedlings did not contain significant levels of pchlide reductase mRNA, whereas stems of light-grown plants of the same age accumulated substantial amounts of the message. These results suggest that light and the developmental age of the tissue affect regulation of lpcr expression in pine. PMID- 1494357 TI - Comparative studies on the postantifungal effect produced by the synergistic interaction of flucytosine and amphotericin B on Candida albicans. AB - A turbidometric method was used to measure Candida albicans yeast cell growth and to quantitate the postantifungal effect (PAFE) after exposure to various concentrations of flucytosine and amphotericin B, alone and in combination, for 2 hr at 30 degrees C. The drug concentrations used in the PAFE assays were determined by initial MIC and FIC (fractional inhibitory concentration) evaluations. The PAFE was calculated by the difference in time (hr) required for growth of the control and test cultures to reach the 0.5 absorbance level following removal of the drug by dilution. A synergistic PAFE was evidenced with combinations of the two drugs at concentrations below their individual MICs. Combinations of flucytosine (0.012 to 0.049 micrograms ml-1) and amphotericin B (0.195 to 0.39 micrograms ml-1) produced PAFEs ranging from 6.3 to 21.8 hr. These PAFEs persisted from 0.3 to 14.7 hr longer than those achieved when each of the two agents was assayed separately. PMID- 1494359 TI - Extensive dermatophytoses caused by Trichophyton mentagrophytes and Microsporum canis in a patient with AIDS. AB - Retrospective studies have shown the occurrence of episodes of deep or superficial fungal infections in 58 to 81% of HIV/AIDS patients as a result of impairment of cell immunity. We describe a case of disseminated cutaneous dermatophytoses caused by Trichophyton mentagrophytes and Microsporum canis in a patients with AIDS. Diagnostic and therapeutic problems in relation to this unusual presentation are emphasized as well as the importance of an early mycologic diagnosis to prescribe antifungal therapy. PMID- 1494358 TI - Isolation of dermatophytes from clinically normal sites in patients with tinea cruris. AB - Sixty patients clinically suspected of tinea cruris were studied by collecting skin scrapings from the site of their lesions and six clinically normal sites including the thighs, scrotum, crural clefts, natal cleft and the web between their 4th and 5th toes. Dermatophytes were detected in scrapings in 46 (77%) and by culture in 36 (60%) patients from lesions. Trichophyton rubrum was isolated from 32 and Epidermophyton floccosum from 4 patients. Dermatophytes were also isolated with maximum isolation from the scrotum, crural clefts and the natal cleft in that order. Thus, when tinea cruris is treated with topical antifungal agents they should be applied also to the potential carriage sites to prevent recurrence. PMID- 1494360 TI - Antifungal activity of allylamines on Epidermophyton floccosum: scanning electron microscopy study. AB - The action of allylamine antifungal agents on Epidermophyton floccosum was studied using scanning electron microscopy. After 7 days of culture on Sabouraud dextrose agar, Epidermophyton floccosum samples were brought in contact with concentrations of 0.2 and 2 micrograms ml-1 and 0.01 and 0.1 micrograms ml-1 of naftifine and terbinafine, respectively. Lesions observed after 24 h, 3 and 7 days of contact were mainly on the structure and rigidity of the mycelial and macroconidial wall. They were characterized by hyphal ballooning and twisting and by apical bulbous bulges. Deterioration of macroconidia was characterized by wall exfoliation. The intensity of the deterioration depended on the dose and only slightly on the length of time that the sample and the antifungal drug were in contact. PMID- 1494361 TI - Tremorgenic mycotoxins produced by strains of Penicillium spp. isolated from toxic Poa huecu parodi. AB - Seventeen strains of Penicillium spp. have been isolated from Poa huecu Parodi from the Zapala zone, exhibiting toxicity to sheet. The following strains have been identified: P. crustosum, cyclopium, notatum, palitans, puberulum, verrucosum, viridicatum and Penicillium spp. The toxigenic capacity of the strains was studied after growing them under suitable conditions. Toxins produced were analysed by thin layer chromatography (TLC). Penitrem A (PA) and Penitrem B (PB) neurotoxins were identified and quantitated in twelve strains; verruculogen (VERR) and fumitremorgen B (FTB) being present in one of them. The effect of these mycotoxins was studied in mice. Neurological symptoms characteristic of the intoxication by tremorgenic toxins and similar to those observed in sheep suffering from 'huecu's disease' were observed. The possible role of these toxins as causative agents of 'huecu's disease' is discussed. PMID- 1494362 TI - Cytotoxicity of Fusarium species mycotoxins and culture filtrates of Fusarium species isolated from the medicinal plant Tribulus terrestris to mammalian cells. AB - Ayurvedic medicine, which uses decoctions made of medicinal plants, is used to cure diseases in many Asian countries including Sri Lanka. Although proper storage facilities for medicinal plants are unavailable in Sri Lanka, neither the potential for growth of toxigenic fungi nor their ability to produce mycotoxins in stored medicinal plants has been investigated. We isolated three Fusarium species, F. culmorum, F. acuminatum and F. graminearum from the medicinal plant Tribulus terrestris. Culture extracts of the 3 Fusarium spp. were cytotoxic to mammalian cell lines BHK-21 and HEP-2. Three toxic metabolites produced by Fusarium spp; T-2 toxin, zearalenone, and diacetoxyscirpenol were also cytotoxic to the mammalian cell lines. The 3 Fusarium spp. grown on rice media produced zearalenone. Plant material destined for medicinal use should be stored under suitable conditions to prevent growth of naturally occurring toxigenic fungi prior to its use. PMID- 1494363 TI - Leprosy vaccine: India questions Venezuelan data. PMID- 1494364 TI - Sacred cows make the best burgers. PMID- 1494365 TI - An interview with Bernadine P. Healy. Interview by Carmella A. Bocchino. AB - In April 1991, Dr. Bernadine P. Healy was appointed director of the National Institutes of Health--the largest biomedical research organization in the world. In assuming this position, Dr. Healy became the nation's premier woman in science and broadened the opportunities for women in an arena traditionally dominated by men. She has aggressively tackled the research agenda for NIH and assured the inclusion of women's health issues. Using her leadership, Dr. Healy has redefined the director's role, broadened women's visibility in science, and defended the extensive Women's Health Initiative and the Administration's stand on fetal tissue research. PMID- 1494366 TI - The impact of leadership upon productivity. AB - Shifting from management to leadership behaviors increases productivity. Five specific behaviors, but particularly the ability to be an excellent role-model, are vital in enhancing and supporting productivity. PMID- 1494367 TI - Assessment of attitudes toward cost-containment needs. PMID- 1494368 TI - Cost reductions Part 2: an organizational culture perspective. AB - Part One of this series described how an Operations Improvement process, computer simulation, and a focus on the dollars per patient day or unit of service ($PPD) can enhance a hospital's cost-reduction efforts. Part Two will address the organizational culture issues that can hamper or support nursing's cost-reduction efforts. PMID- 1494369 TI - Economic awareness of registered nurses employed in hospitals. AB - The basic knowledge and beliefs of RNs in three hospitals in the midwest are described. Nurses lack basic knowledge of how economics affect their practice, yet desire to learn more about economic issues related to nursing practice and health care. PMID- 1494371 TI - Blaming the victim. PMID- 1494370 TI - Ethical concerns regarding cardiac retransplantation. AB - Health care professionals face many ethical dilemmas regarding cardiac transplantation and retransplantation. A thorough understanding of ethical theories and careful examination of each case encourages decisions reflective of the values of the health care team. PMID- 1494372 TI - Bioethical issues in the use of technology. PMID- 1494373 TI - Creating a healing environment: the nurse manager's challenge. AB - Environments can create positive attitudes or they can induce negative feelings. The nurse manager's responsibility is to understand how different environmental designs can reduce patient and staff anxiety and stress. The patient care unit should support staff and patients and provide a caring, healing environment. Chapman makes the important point to "Do everything you can think of to take better care of your employees so that your employees in turn will take better care of patients" (1990, p. 19). Happy, cared-for staff will take excellent care of patients and create a healing environment. PMID- 1494374 TI - Specialty beds: taking the $$ pressure off. PMID- 1494375 TI - Transition ... a time for change. PMID- 1494376 TI - [Reciprocal inhibition of human motor neurons at different firing rates]. AB - Reciprocal inhibition (RI) has been studied for its effect on repetitive firing of single motoneurons in the extensor carpi ulnaris and soleus muscles of healthy subjects. The peristimulus time histograms (PSTHs) were plotted for different mean firing frequency of motoneurons. Changes in the interspike interval duration were analyzed. It was shown that the "effectiveness" of reciprocal volleys (as it was previously shown for other types of inhibition) depended on the firing rate of a motoneurons. It was found out that RI duration derived from the PSTH, duration of the "effective part" of the interspike interval, rate of the interspike interval lengthening depended on the motoneuron firing frequency. It was also found that the inhibitory effect of the motoneuron firing was pronounced mostly at its low-frequency range. The dependence of "effectiveness" of an inhibitory volley on the moment of its arrival within the interspike interval was analyzed as well. PMID- 1494377 TI - [Cytophotometric and electrophysiologic analysis of the role of the celiac plexus in maintaining temperature homeostasis in cold stress in rats]. AB - The role of the celiac plexus in maintaining temperature homeostasis in rats during cold stress was studied histochemically, ultrastructurally, and electrophysiologically. Inhibition on efferent impulses in preganglionic (splanchnic) nerves and facilitation in postganglionic (superior mesenteric) nerves during a short-term cold exposure leading to slight hypothermia were found. In cold-exposed animals after the celiac plexus decentralization, the neurons showed an increase in the fluorescence intensity and activity of energy metabolism enzymes, hyperplasia of fine structures responsible for protein synthesis and energy supply of cells. It is suggested that during cold stress when efferent impulse flow in preganglionic nerves markedly decreases, the celiac plexus becomes a regulatory centre for autonomic functions involved in the maintenance of temperature homeostasis. PMID- 1494378 TI - [Vascular and autonomic disorders of the spinal cord in dystopia of the spinal motor segment]. AB - Microcirculation disorders may cause functional deviation in gray matter cells of the spinal cord. One of the setting moments of the disorders is the subluxation of a vertebra as a result of the disturbance in carrying ability of the spinal disc in case of spinal osteochondrosis. In this position the soft tissues of the spinal motional well innervated segment are stretched, which induces irritation in the segmental part of the spinal cord including vegetative nervous structures. Subluxation of a vertebra causes changes in the structures and in the microcirculation vessels which grow simultaneously and this permits supposing their interrelation. PMID- 1494379 TI - [Evaluation of the cat brain activation using ECoG on the cat striate cortex]. AB - The striate cortex electrocorticogram has been analyzed in 12 cats in following states: at rest with the eyes closed and with the eyes opened; after light electrical stimulation of ears; somnolence; eye opening after somnolence+; barbituric sleep. The behaviour of cats was controlled and the state of emotional excitability was determined. Spectral and periodometric analysis of ECoG has revealed state-dependent differences of cats in power spectra from 2 frequency ranges (2.8-5.0 Hz and 13.8-20.8 Hz). It is suggested that the ratio of ECoG power spectra in these frequency ranges can be used to evaluate the brain activation of cats. PMID- 1494380 TI - [Effect of exogenous acetylcholine on potassium currents of motor nerve endings in the frog]. AB - Mechanisms of the exogenic acetylcholine (ACh) effect on ionic currents of nerve endings (NE) were investigated by extracellular recording of NE at the cutaneous pectoris muscle of frog. It was found that ACh in concentrations 0.1-0.6 mmol/l increased the third phase of the nerve ending response, while in concentrations 0.7-2.0 mmol/l-decreased it. Tubocurarine and atropine did not alter the ACh effect. It has been also revealed that growth of the third phase of NE response, induced by ACh, occurs in the presence of calcium channel blockers and disappears under the influence of 4-aminopyridine and tetraethylammonium. In calcium-free solution or when the calcium current is blocked the suppressive effect of ACh disappears. The mechanisms of exogenic and endogenic ACh effects on the potential sensitive and calcium-activated potassium NE currents are discussed. PMID- 1494381 TI - [Strychnine-induced changes of the membrane and postsynaptic potentials in neocortical neurons]. AB - Intracellular responses of neurons of the suprasylvian gyrus to the intracortical stimulation (ICS) before and after superficial application of strychnine were investigated in experiments on immobilized and unanaesthetized cats. The normal cortex neurons reacted to ICS by monosynaptic EPSPs followed by IPSPs. Strychnine application triggered the epileptiform activity and appearance in neurons of paroxysmal depolarization shifts of the membrane potential (MP) which were replaced by hyperpolarization potentials. An increase and summation of the latter elicited the MP enlargement and either reduction or suppression of background spike activity. Intracellular injections of EGTA blocking the membrane calcium dependent potassium conductivity (gK(Ca)) have eliminated the hyperpolarization potentials. Development of epileptiform activity was accompanied by depression of IPSPs and increase of the monosynaptic EPSPs. The contribution of gK(Ca) and of postsynaptic inhibition to the epileptogenesis is discussed. PMID- 1494383 TI - [Role of structures of the ventrolateral medulla oblongata in the regulation of cardiovascular activity]. AB - The review presents information on morphology, afferent and efferent connections of the ventrolateral medulla, mediator characteristics of neurons within the rostral and caudal parts of the ventrolateral division of the medulla, functional organization of the structures involved in the cardiovascular control. PMID- 1494382 TI - [Neurophysiologic changes and bound calcium dynamics during the elaboration of associative learning in Helix lucorum]. AB - Neurophysiological effects and dynamics of bound calcium (Ca-b) in command neurons of defense behavior (LP11 and RP11) during food aversion conditioning were studied in snail Helix lucorum. It was found that during associative learning both conditioned reaction and nonspecific facilitation of sensory responses were determined in neurons. The nonspecific facilitation of sensory responses was similar to that found during sensitization development in neurons. However, conditioned response appeared 30 min later than long-term sensitization development. Specific dynamics of the Ca-b level in neurons was obtained after three and more conditioning. The dynamics of the Ca-b level correlated with neurophysiological effects and differed from those measured during sensitization development. It is suggested that molecular mechanisms underlying associative learning and sensitization are different in a command neuron of defense behavior in the snail. PMID- 1494384 TI - [Mechanisms of suprasegmental correction of the work of generators of cyclic motor reactions]. PMID- 1494385 TI - [The intra-carotid amobarbital test--indications--procedure--results]. AB - In presurgical assessment of epilepsy, the intracarotid amobarbital procedure (IAP) is used for the detection of functional asymmetries of the cerebral hemispheres with respect to cognitive functions. The IAP permits a precise and reliable determination of patterns of language dominance, although analysis of the lateralization of specific memory functions is constrained by methodological problems. In addition, the IAP yields information on the lateralization of other cognitive functions such as attention, consciousness, and emotion. It may also serve as a means of delineating the primary epileptic focus. Furthermore, the IAP may also be helpful in the assessment of non-epileptic patients prior to elective operations in brain regions relevant to cognition. PMID- 1494387 TI - [Prospective follow-up of neuropsychological deficits after cervicocephalic acceleration trauma]. AB - 30 patients with acute cervico-cephalic syndrome following whiplash injury (neck and head pain, vegetative symptoms and subjective complaints of impaired mental functions) without neurological deficits were investigated in a prospective follow-up of 3 months with neuropsychological examination in the acute phase (x = 5.7 days) and again 6 and 12 weeks after the accident. Attention, concentration, cognition and verbal and visual memory functions were quantified by neuropsychological tests, and changes over the observation period were analysed. In the acute phase all neuropsychological functions were below the individual's normal level. Deficits in attention and concentration recovered within the first 6 weeks. Further recovery within the following 6 weeks were observed in visual memory, imagination and analytic capacity. The capability of verbal memory and abstraction, cognitive selectivity and information processing speed was impaired for a longer time and first recovered after 12 weeks. In conclusion, intraindividual neuropsychological deficits following whiplash injury can be quantified and monitored to show the time course of recovery. Thus in clinical and forensic practice the diagnosis of a pseudoneurasthenic or even "neurotic" syndrome in acute whiplash injury should be made with caution. PMID- 1494386 TI - [Cystic abnormalities of the brain: stereotaxic diagnosis and therapy]. AB - We present the stereotactic treatment and evaluation of 33 patients with congenital cysts of the brain (6 cavum septi pellucidi/cavum vergae cysts, 5 suprasellar cysts, 3 intraventricular cysts, 4 cysts of the interhemispheric fissure, 4 cysts of the cerebral convexity, 5 supracollicular cysts, 3 cysts in the cisterna ambiens, 2 temporomedial cysts and 1 cyst in the pontomesencephalic junction). The patients were seen during an 8-year period (1984-1992) and had a mean follow-up time of 27 months. In 23 patients with cysts in or near the cerebral midline or at the cerebral convexity, a stereotactic ventriculocystostomy resulted in clinical improvement with diminished cyst size. Another 8 patients with relatively small cysts profited from stereotactic aspiration of the cyst contents. Three complications (bleeding, aseptic meningitis, catheter infection) remained without sequelae. The stereotactic procedure is the treatment of choice for these lesions because of the low operative risk, its minimal invasiveness and the possibility of distinguishing primary congenital cysts from other pseudocystic lesions. In well-chosen cases the carefully planned stereotactic internal derivation of the cysts in the ventricular system led to a long-lasting beneficial effect. Open craniotomy or shunting procedures can be avoided for most cases of congenital intracranial cysts. PMID- 1494388 TI - [The status of afebrile infantile convulsions within the epilepsy spectrum--a follow-up of 55 patients]. AB - In an earlier study we observed 411 patients with cerebral convulsions, 118 of whom had the first convulsion during the 1 year of life. Among these 118 children we found 76 with afebrile convulsions. In this study we present the development and outcome in 55 patients with afebrile convulsions in the 1 year of life which could be observed for some years, most of them up to the present. In 25 infants the fits started in the newborn period, and in 30 infants after the 1 month; they were divided into groups with and without risk factors in the history. Benign neonatal convulsions were found in about one-third of children, with a good prognosis. These convulsions are divided into a dominantly inherited but rarely observed form and idiopathic benign neonatal convulsions. In contrast, among the newborns with risk factors in the history we found only half with a positive development. The results in the 30 infants with convulsions after the 1 month were similar with respect to risk factors in the history of risks. The 15 infants without risks had a good prognosis. Only 3 patients had oligoepilepsy. However, in the 15 patients with risks only 3 developed normally, 6 had no fits, but were neurologically or mentally handicapped, and 7 had fits and disability. We believe that afebrile convulsions without risk factors after the 1 month could be considered a late manifestation of benign newborn convulsions.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1494389 TI - [Multiple sclerosis and subcortical arteriosclerotic encephalopathy as clinical differential diagnosis]. PMID- 1494390 TI - [Computerized tomography markers of morphologically confirmed hemorrhagic brain infarct]. AB - Radiological differentiation between hemorrhagic infarction and intracerebral hemorrhage is important for patient management. To ascertain CT features of hemorrhagic infarction, we studied the findings in 19 cases with autopsy-proven hemorrhagic infarction. Most cases had multiple, mainly cortically located, small hyperdensities. However, some presented with a single hyperdensity, deeply located, that could be mistaken for primary intracerebral hematoma. Hemorrhagic infarctions usually present as multiple, small hyperdensities within a hypodense area compatible with an arterial territory. The shape can be round, slitlike, curvilinear, or spotted. Most often the hyperdensities are located cortically; however, some larger, deeply located hyperdensities may falsely suggest primary intracerebral hematoma. Some guidelines for a more reliable radiological separation between hemorrhagic infarctions and intracerebral hematomas are suggested. PMID- 1494391 TI - [Repeated treatment of subtotal vertebrobasilar stenosis with tissue plasminogen activator (tPA)]. AB - We report on the successful repeated treatment of a patient with rapidly progressive severe brain-stem stroke by application of I.V. tissue plasminogen activator (tPA). This treatment twice led to a prompt remission of severe brain stem symptoms, although a permanent therapeutic success could not be achieved. Unfortunately, the patient died a few days later from pneumonia and sepsis. Necropsy revealed bilateral partial brain-stem infarctions and a subtotal stenosis of the vertebrobasilar junction with superimposed fresh thrombus. The clinically dramatic response to tPA indicates that this type of treatment is potentially successful in high-grade subtotal basal cerebral artery stenosis with progressive stroke symptoms. In particular, application of tPA should be considered if stroke progression cannot stopped by therapeutic heprinization. A prospective randomized oligocentric study is advocated. PMID- 1494392 TI - [Transcranial Doppler contrast study--an ideal method for detection of paradoxical cerebral embolism?]. AB - Cerebral paradoxical embolizations can easily be detected by transcranial Doppler investigations using intravenous echo contrast medium. In some cases of TIA or stroke without vascular or cardiac disease, this method will reveal a right-to left vascular shunting (e.g. by a patent foramen ovale). However, demonstrating a leakage through the atrial septum does not necessarily reveal the source of an embolus or the cause of the stroke. Thus the question of prolonged antithrombotic therapy must be decided in each individual case. PMID- 1494393 TI - [Multiple meningiomas in different compartments of the cerebrospinal axis]. AB - Multiple meningeomas in the absence of Recklinghausen's disease are rare and usually occur in a single compartment of the neuroaxis. Multiple meningeomas in different neuroaxial compartments are an even rarer condition, only a few cases having been reported. We describe four cases, each with two meningeomas in different compartments of the neuroaxis. Their peculiarity consists in the fact that the different tumours developed at different times and locations in the supratentorial and spinal regions. The radiological and operative findings are described. The possibility of dissemination via the cerebrospinal fluid or blood or of a multifocal origin or genetic predisposition is discussed. PMID- 1494394 TI - [15+/-deoxyspergualin, hope for patients with multiple sclerosis?]. PMID- 1494395 TI - [Current therapy of multiple sclerosis--high-dose intravenous therapy with corticosteroids]. PMID- 1494396 TI - [What is multisystem atrophy? Comments to the contribution by B. Ziegler, W. Tonjes, W. Trabert and H. Kolles. Cerebral multisystem atrophy in a patient with depressive-hallucinatory syndrome]. PMID- 1494397 TI - Pancreas transplantation: from experiment to therapy. PMID- 1494398 TI - Simultaneous pancreas and kidney transplantation: a feasible procedure in selected patients. AB - We analyzed the overall results of 24 simultaneous pancreas and kidney transplantations (SPK), performed in our hospital between April 1986 and June 1990. All patients had type I diabetes mellitus and end-stage renal failure. We used bladder drainage of the pancreatic exocrine secretions through a duodenocystostomy. The blood vessels of both grafts were anastomosed to the iliac vessels. The immunosuppressive management was triple-therapy with cyclosporin, azathioprine and prednisone. All organs were transplanted without matching donors and recipients for HLA. At the time of transplantation, mean recipient age was 37 yr; the average duration of diabetes was 22 yr. After disappointing results in the first 4 patients, the pancreas was placed intraperitoneally instead of extraperitoneally and the antibiotic drug regimen was altered. In the second group (n = 20), patient survival was 100%; 1-yr pancreas and kidney graft survival were 65 and 62%, respectively. Duration of hospitalization and pancreas and kidney graft loss were positively correlated with the number of rejection episodes. After 1 yr of follow-up, the mean creatinine clearance was 62 ml/min and the mean HbA1c was 5.5%. Blood glucose levels and oral glucose tolerance tests were also normal. We conclude that patient and graft survival after SPK are satisfactory, although rejection-related morbidity is still a major problem. PMID- 1494399 TI - Lowering of plasma glucose concentration in septic cancer-bearing patients: metabolic significance. AB - Previous work has indicated that 40-50% of glucose intake is oxidized in normal humans with protein-sparing effect. In contrast, the catabolic stressed patient is hyperglycaemic with decreased glucose oxidation and protein wasting. This study evaluated whether the plasma glucose concentration alone would be a reliable indicator of efficient glucose utilization and protein sparing in the critically ill septic cancer patients receiving glucose infusions. Glucose turnover, glucose concentration, nitrogen excretion, oxygen consumption, and glucose oxidation were measured in 8 septic cancer-bearing patients during a glucose infusion of 4.0 mg/kg/min followed by the infusion of insulin with the same glucose load. During glucose infusion without insulin the glucose concentration was 11.8 +/- 1.4 mmol/l, glucose oxidation 10 +/- 5% of glucose tissue uptake, and nitrogen excretion 9.0 +/- 1.3 mg/kg/h. During the euglycaemic clamp the glucose concentration was 3.8 +/- 0.2 mmol/l, glucose oxidation increased to 45 +/- 6% of glucose tissue uptake (p < 0.001), and nitrogen excretion dropped to 6.8 +/- 1.2 mg/kg/h (p < 0.001). The glucose concentration was greater than 10 mmol/l in 4 patients and between 6.9 and 9.3 mmol/l in 4 patients after glucose infusion alone. Despite this difference in initial glucose concentration, normalization of plasma glucose to less than 5 mmol/l with insulin resulted in the same decrease in nitrogen excretion and improvement in glucose oxidation. We conclude that, independent of the initial glucose concentration, maintenance of euglycaemia with insulin appears to be a good indicator of efficient glucose utilization and protein sparing in septic cancer-bearing patients receiving glucose as the primary mode of nutritional support. PMID- 1494400 TI - Peritoneal tuberculosis in two young immigrants with fever of unknown origin. AB - Two patients with long-standing fever and weight loss underwent extensive diagnostic procedures before peritoneal tuberculosis was diagnosed by explorative laparatomy. By that time they had developed signs of intestinal obstruction. Both recovered after treatment, but one developed serious neurological complications, which could not be explained. Peritoneal tuberculosis is a manifestation of tuberculosis that is often difficult to diagnose. It should be borne in mind when diagnosing patients with fever of unknown origin, especially if they are originally from countries with a high prevalence of tuberculosis. PMID- 1494402 TI - Growth hormone: secretion and administration in catabolic adult patients, with emphasis on the critically ill patient. AB - Critical illness, surgery and hypocaloric feeding are accompanied by a high rate of total body nitrogen loss. Loss of body protein, occurring despite adequate nutrition, results in increased incidence of infection, poor wound healing, skeletal muscle weakness and increased mortality. Growth hormone (GH) administration together with nutritional support attenuates protein catabolism. This review focuses on normal GH physiology and the administration of GH in adult catabolic patients. PMID- 1494401 TI - Kikuchi's lymphadenitis: report of a Yersinia enterocolitica-associated case and an overview of aetiology and clinical outcome. AB - Kikuchi's lymphadenitis (KL; histiocytic necrotizing lymphadenitis without granulocytic infiltration) is a generally benign, febrile disorder of unknown aetiology with distinct histological features. To date, a minority of cases reported have been associated with infectious agents. A typical pathological case of KL is described where involvement of Yersinia enterocolitica was shown by an indirect immunofluorescent assay applied to lymphatic tissue. The case is discussed with emphasis on recent insight into the course and aetiology of KL. PMID- 1494403 TI - A newly discovered function of the erythrocyte: transport of immune complexes to the liver. PMID- 1494404 TI - Some skeletal dimensions of males with isolated gonadotrophin deficiency. AB - This is a retrospective study of stature and bone age before and during androgen substitution for hypogonadotrophic hypogonadism in 25 males. Before androgen treatment, stature tends to be low for chronological age but normal for bone age. Treatment results in normal final height. Growth in length of metacarpal bone II (MC II), measured on hand radiographs, mimics growth in height. From measurements of total bone width of MC II and combined cortical thickness of MC II, the cortical area (indicating bone mass) and the relative cortical area (indicating bone density) were calculated. Bone mass was well within the limits of a published control series, both before and during androgen treatment. Bone density, however, was, without exception, below the P50 for controls prior to androgen treatment, and increased only slightly during treatment. It is concluded that prepuberal deficiency of androgen, possibly in early infancy, causes a permanent defect in bone density which is only marginally corrected by later androgen treatment. PMID- 1494405 TI - Infection with Dengue virus. AB - We report a male Caucasian, with a Dengue virus infection imported from Thailand to The Netherlands. General characteristics of the disease are presented and the supposed pathogenetic mechanisms of the disease are discussed. PMID- 1494406 TI - Dialysis associated mucormycosis and desferrioxamine treatment: a case report with review of the role of oxygen radicals. AB - A hemodialysis patient with pulmonary and cerebral mucormycosis is reported. Recently the occurrence of this infection in dialysis patients has been associated with desferrioxamine (DFO) treatment. A causal relation seems likely, but has not been proved. Several pathogenetic mechanisms are discussed, in particular the influence of DFO on host neutrophil defenses through a decreased oxygen radical production. PMID- 1494407 TI - Mineralocorticoid excess due to precursors only in a patient with adrenal cortical carcinoma. AB - A patient with carcinoma of the adrenal cortex presented with mineralocorticoid excess due to hypersecretion of deoxycorticosterone, which is exceedingly rare. Backache was the only symptom and an unexplained hypokalaemia was the only sign. Because of the abnormal synthesis of steroid precursors in these tumours a urinary steroid profile may be helpful as a diagnostic tool in such cases. PMID- 1494408 TI - Alternative stress methods for the diagnosis of coronary artery disease. AB - Bicycle exercise and treadmill exercise are the commonest devices used in the evaluation of coronary artery disease. However, not all patients are capable of performing a maximal exercise test due to orthopaedic, vascular or pulmonary disease, poor physical condition and motivation. Alternative tests as a reliable substitute for the more conventional methods have been proposed, such as right atrial pacing, arm ergometry, handgrip test, cold pressure test, and inotropic stimulation. In particular, pharmacological stress testing with dipyridamole (and recently with adenosine and dobutamine) in combination with radionuclide techniques has gained much interest. This review will consider the usefulness and role of alternative stress testing to provoke myocardial ischaemia, with emphasis on pharmacological stress testing in conjunction with thallium-201 myocardial perfusion scintigraphy. PMID- 1494409 TI - Polycythaemia vera. PMID- 1494410 TI - Arachnoid cysts of the middle cranial fossa. AB - In 18 cases of temporal arachnoid cysts the etiology, clinical and radiographic findings, surgical treatment, and outcome are reviewed. Cysts of the middle cranial fossa are susceptible to trauma, which may cause bleeding either into the cyst or into the subdural space. CT or MRI scans are diagnostic in arachnoid cysts. In cases of intracranial mass lesion with displacement of the midline structures and increasing ICP, osteoplastic craniotomy is performed and the medial wall of the cyst is resected down to the tentorial notch, with opening into the basal cisterns. There were no operative or postoperative complications in 18 consecutive cases. However, one boy required a cystoperitoneal shunt 3 months later as a result of hydrocephalus following subdural hematoma and two other patients were also subsequently shunted. Asymptomatic arachnoid cysts are discussed with the respect to brain function and potential risks. PMID- 1494411 TI - [Autonomic nervous system disorders in 230 cases of basilar impression and Arnold Chiari deformity]. AB - Within the period of 1971 to 1989 we operated on 230 cases of craniocervical malformations characterised by 189 cases of basilar impression associated with Arnold-chiari malformation, 28 cases of isolated basilar impression and 13 cases of Arnold-Chiari malformation. Autonomic disturbance was observed in 136 (59.1%) cases: sexual disorders like reduced potency and impotency were observed in 86 (60.9%) out of 141 male patients, urinary symptoms in 39 (17%) patients; and other autonomic features like dyspnea, anhidrosis, hyperhidrosis, Claude Bernard Horner syndrome and constipation in 41 (17.8%) patients. PMID- 1494412 TI - Basilar impression and Arnold-Chiari malformation. Surgical findings in 209 cases. AB - The surgical findings observed in a series of 209 consecutive patients with craniovertebral anomaly are presented. The high prevalence of basilar impression in the Northeast of Brazil is noteworthy. There were 28 (13.3%) patients with basilar impression alone, 10 (4.7%) cases of pure Arnold-Chiari malformation and in 171 (81.8%) cases the basilar impression was associated with Arnold-Chiari malformation. This study reflects our surgical experience of the pathology in a 17-year period (1971-1987). It reflects also the peculiarities of neurosurgical practice in an undeveloped region of this Country. The literature is extensively reviewed. PMID- 1494413 TI - [Initial experiences with a new cerebrospinal fluid collection system]. AB - Due to clinical requirements and to improve the handling of CSF drainage set we developed a new concept, consisting of an arrangement of constructions, which are already available. Besides other advantages, the set provides an ICP monitoring, a pump device and a protection of the air filter of the collecting tank for safer transport. Opening the system for the performance of diagnostic or therapeutic manoeuvres can therefore be avoided. This new equipment has been tested in 28 patients having a ventricular or lumbar CSF drainage with good results and has been quickly accepted by the medical staff. The construction is described in detail. PMID- 1494414 TI - Supratentorial arachnoidal cyst with intracystic and subdural haematoma. AB - A case of a arachnoidal cyst with intracystic bleeding and subdural haematoma is reported. The association of an arachnoidal cyst in the middle cranial fossa with a subdural haematoma or intracystic bleeding is emphasised. The diagnosis of such lesions, the nature of the pathology and therapy are discussed. PMID- 1494415 TI - Von Hippel-Lindau disease: analysis of two families. AB - In this report we present two families with von Hippel-Lindau syndrome. We operated on haemangioblastomas in two members, one from each, in our clinic. In the first family we saw 17 lesions in 9 members. Although in the first family carcinoma of the kidney was often observed, in the second family retinal haemangioma was found to be predominant, namely, in eight out of nine patients. In both families there were 11 patients with retinal haemangioma; of these, 9 patients were blind (82%). In 6 patients with retinal haemangioblastoma blindness was unilateral and bilateral only in one. All the patients with renal carcinoma were male and died young. In one of our patients with renal carcinoma we found metastatic lesions in the distal and proximal parts of the femur, vertebral arch, cranium and the thoracic wall. In these two families 23 members had 32 lesions, from which eleven were retinal haemangiomas (3 + 8), nine haemangioblastomas of CNS (5 + 4), one a renal cyst (0 + 1), eight renal carcinomas (7 + 1), two pancreatic cysts (1 + 1) and one liver cyst (0 + 1). PMID- 1494416 TI - [Chronic subdural hematoma as a cause for blindness]. AB - The uncommon complication of bilateral blindness resulting from a decompressive neurosurgical procedure is presented by the case of a 51-year old patient suffering from a traumatic chronic subdural haematoma. A breakdown of the altered vasoregulation of the optic nerves due to papilledema at the time of intracranial pressure drop is supposed to be the etiological background of optic atrophy and consequent amaurosis. The causal relationship of accident trauma and blindness in the presented case is pointed out. PMID- 1494417 TI - Advances at the cutting edge. PMID- 1494419 TI - Must I take filthy money? PMID- 1494418 TI - The theatre of war. Interview by Kathy Stodart. PMID- 1494420 TI - Mental health. New Act signals changes. PMID- 1494421 TI - Mental health. Unit copes with new law. PMID- 1494422 TI - Men in uniform. PMID- 1494423 TI - Pushing nursing. Interview by Teresa O'Connor. PMID- 1494425 TI - Health law: defining misadventure. PMID- 1494424 TI - Work test on glutaraldehyde. PMID- 1494426 TI - Incorporating digitized video: how do you begin? PMID- 1494427 TI - Using IVD for independent nursing skill development. PMID- 1494428 TI - Digitized video: today and tomorrow. PMID- 1494430 TI - Novelty, suppression, and editorial boards. PMID- 1494429 TI - Senge's, The Fifth Discipline, suggests solutions for nurse educators. PMID- 1494431 TI - Glaucoma associated with epithelial downgrowth controlled with Molteno tube shunts. AB - We report two histopathologically proven cases of epithelial downgrowth in which the secondary glaucoma was controlled by a double-plate Molteno tube shunt and useful vision restored with a penetrating keratoplasty. The combination of a tube shunt and penetrating keratoplasty may be indicated to maintain useful vision in advanced cases of epithelial downgrowth associated with secondary glaucoma. PMID- 1494432 TI - THC:YAG laser sclerostomy: the resident experience. AB - Retrospective review of 14 consecutive THC:YAG laser sclerostomies done without the use of anti-metabolites revealed a uniform closure of the filtering bleb within 6 months of follow up. Also, the sclerostomy site was closed by iris or fibrous tissue. Based on these findings, I recommend that the present THC:YAG laser sclerostomy protocol be altered to allow for antimetabolite usage, prevention and treatment of iris prolapse, and control of intraocular inflammation. PMID- 1494433 TI - Anterior chamber tube shunt to an encircling band (Schocket procedure) in the treatment of refractory glaucoma. AB - We reviewed a series of 42 eyes in patients with refractory glaucoma who had undergone a Schocket procedure. The mean follow up was 17.5 months; the minimal follow up, 8 months. The success rate was 81%, with "success" defined as either (1) an intraocular pressure less than 21 and greater than 5 mm Hg, with a pressure reduction of at least 10%, and less or no medication; or (2) a pressure reduction of at least 30%, with no change of medication. When eyes with a loss of more then one Snellen line of visual acuity were interpreted as failures, the success rate dropped to 61%. Forty percent of all cases required revision. In four cases, the shunt had to be removed (three cases due to hypotony and one secondary to conjunctival erosion). These results are in the range of those obtained by other investigators using this technique or other tube-shunt procedures. PMID- 1494434 TI - Intraocular lens insertion during vitrectomy. AB - Vitrectomy was performed in 10 patients in combination with posterior chamber intraocular lens (IOL) insertion. Indications for vitrectomy included traumatically dislocated cataract, choroidal hemorrhage, epiretinal membrane, lens involving intraocular foreign body, vitreous hemorrhage, and extruded anterior chamber IOL. Postoperative visual acuity improved in each case. The main advantages of simultaneous IOL insertion, in selected cases, are reduced cost and inconvenience, and more rapid visual rehabilitation. PMID- 1494436 TI - The wedge punctoplasty for treatment of punctal stenosis. AB - We describe a new instrument, the Reiss punctal punch, which is specifically designed to performa "wedge" punctoplasty. The Reiss punctal punch was used alone to treat three eyelids of three patients, and in conjunction with horizontal tightening of the eyelid to treat 35 eyelids of 18 patients with symptomatic epiphora related to punctal ectropion with secondary punctal stenosis. After a mean follow up of 12 months, 36/38 (95%) of the eyelids demonstrated a patent punctum, and symptomatic relief was achieved in 35/38 (92%) of the eyes. PMID- 1494435 TI - Evaluation of silicone gel as a long-term vitreous substitute in non-human primates. AB - Two preparations of silicone gels were evaluated as long-term vitreous substitutes in the vitrectomized and lensectomized eyes of primates. Both preparations were injected in liquid form and polymerized in the vitreous cavity. There was no toxic effect on the ocular structures up to 13 months after implantation. Fundus examination and fluorescein angiography were possible through the less rigid gel, whereas the preparation with higher rigidity consistently appeared cloudy. PMID- 1494437 TI - YAG laser demonstration of the anatomy of the lens nucleus. AB - I used YAG laser energy to demonstrate the position and surface of the core of the lens nucleus and to prove the existence of the radial structure of the lens nucleus. Not only does hydrodissection of the epinuclear layers from the nuclear core demonstrate the existence of an anatomical substrate, but also radial fracturing of the nucleus both in phacoemulsification and planned extracapsular surgery can make use of these anatomical features to achieve smaller incisions and thereby smaller wounds. PMID- 1494438 TI - Cyclodialysis cleft following holmium laser sclerostomy, treated by argon laser photocoagulation. AB - I report, to my knowledge for the first time, a case of inadvertent cyclodialysis cleft formation as a complication of holmium laser sclerostomy. Argon laser photocoagulation was used successfully to repair the cleft. PMID- 1494439 TI - Ohmmeter-guided nasolacrimal intubation. AB - Retrieval of steel probes via the inferior meatus of the nose in monocanalicular and bicanalicular nasolacrimal intubation can be a tricky maneuver, possibly complicated by bleeding from lacerated soft tissue around the inferior turbinate. Using a low-voltage device (essentially, an ohmmeter) to assure contact between the retrieval hook and the distal end of the steel probe greatly facilitates the procedure. PMID- 1494440 TI - Treatment of scleromalacia perforans with dura mater grafting. AB - We describe, to our knowledge for the first time in the English literature, the successful use of cadaveric dura mater in reinforcing the sclera in a rheumatoid arthritis patient with scleromalacia perforans. PMID- 1494441 TI - Lack of toxicity of intravitreally administered interferon alpha-2a. AB - We investigated the toxicity of single doses of intravitreally administered interferon alpha-2a in albino rabbits. Following injection of interferon in doses of 40,000, 80,000, 160,000, 320,000, and 640,000 IU/0.1 mL, no significant histologic changes were detected by light and electron microscopy. Photopic and scotopic electroretinography showed no alteration of retinal function. PMID- 1494442 TI - A superior and inferior orbital rim-based exophthalmometer (orbitometer). AB - In exophthalmometry when the lateral orbital rim is used as the instrument's fixation base, any alteration in the rim will render serial measurements inaccurate. The exophthalmometer we describe (technically, an "orbitometer") uses the superior and inferior orbital rim areas as a base of reference, making it particularly useful in lateral orbitotomy procedures. This instrument can be aligned at the midpupil horizontally and vertically with a vertical fixation bar. In addition, a vertical bar gradient scale allows measurement of hypoophthalmos and hyperophthalmos. PMID- 1494443 TI - A new endoscope for ophthalmic microsurgery. AB - We present an endoscope designed for ophthalmic microsurgery. The handpiece contains a charge-coupled device, a solid-state imager (250,000 pixels), and a probe (either 0.89 or 1.5 mm in diameter), including the light guide. The light source is a halogen lamp. The clear views the instrument provides of the ciliary sulcus and ciliary body behind the iris make it useful in secondary posterior chamber intraocular lens implantation using the ciliary sulcus suturing technique, and in endolaser photocoagulation of the ciliary body in end-stage glaucoma. It also is useful in performing vitrectomy in cases in which visualization is difficult because of corneal opacification or fluid-gas exchange. PMID- 1494444 TI - Anterior capsulotomy in the pseudophakic eye. PMID- 1494445 TI - Iridotomy in eyes with pigmentary glaucoma. PMID- 1494447 TI - Associations between microbial species in dental root canal infections. AB - The existence of commensal or antagonistic relationships between microorganisms in the root canals of teeth with apical periodontitis was investigated. Samples were taken from 65 infected human root canals and were analysed according to species, frequency of occurrence and proportion of the total isolated flora. The most frequent species were Fusobacterium nucleatum, Prevotella intermedia, Peptostreptococcus micros, Peptostreptococcus anaerobius, Eubacterium alactolyticum, Eubacterium lentum and Wolinella recta. An odds ratio system was used to calculate positive or negative associations between the isolated bacteria. Strong positive associations were found between F. nucleatum and P. micros, Porphyromonas endodontalis, Selenomonas sputigena and W. recta. There was also a positive association between P. intermedia and P. micros, P. anaerobius and the eubacteria. In general, species of streptococci, Propionibacterium propionica, Capnocytophaga ochracea and Veillonella parvula showed no or negative associations with the other bacteria. The results are consistent with the concept of a special and selective environment occurring in the root canal that is due, in part, to the cooperative as well as antagonistic nature of the relationships between bacteria in the root canal. PMID- 1494446 TI - "Consent" vs "choice" in surgical decision-making. PMID- 1494448 TI - The age-dependence of bacterial presence on oral epithelial surfaces in vivo. AB - Epithelial cells obtained by gentle scraping with a brush tip from the gingival margin of d 11 or 51, adjacent labial mucosa and buccal mucosa of children, adolescents and adults were stained with acridine orange and examined under a fluorescence microscope. The amount of bacteria appearing on the epithelial cells was assessed and the form of the adhered bacteria was evaluated. An age-related descending trend (negative Pearson's r in all sites) could be seen in the number of colonized cells (> 50 bacteria present) in gingival, labial and buccal areas. Adolescents and adults had significantly fewer epithelial cells with colonization of bacteria in the labial and buccal areas compared with children under 6 years. Only cocciformed bacteria were seen associated with the epithelial cells. By studying bacterial adhesion according to methods outlined in the present study, it should be possible to more closely investigate the bacteria-host relationships as they appear in nature. PMID- 1494449 TI - Periodontal pathogens in the shallow pockets of immigrants from developing countries. AB - The aim of this study was to examine the distribution of typical periodontitis associated microorganisms in refugees arriving from non-industrialized countries, and to relate the presence of these organisms to the periodontal condition of the subjects. Thirty males between 35-44 years of age were surveyed. Dental plaque, calculus, gingivitis, loss of attachment, and probing depths were recorded for all surfaces. A total of 90 microbiological samples were taken with paper points from mesial sites of teeth 16, 36 and 41. Microbiological test sites were grouped by probing depths and loss of attachment. Only 16.8% of all surfaces had probing depths > 3 mm, although 90.7% of surfaces had loss of attachment > 1 mm. Twenty one sites with obvious periodontal destruction (PD > 3 mm, LA > 2 mm) showed the greatest recovery of Porphyromonas gingivalis (66.7%). However, 51 sites with minimal periodontal disease (PD < or = 3 mm, LA < 2 mm) and with no gingival recession also showed a relatively high detection frequency of P. gingivalis (34.1%). Twenty-four of these samples came from 12 patients with no pockets > 5 mm and with less than 10% of all sites yielding pockets > 3 mm. The detection frequencies of Prevotella intermedia (91.6%), Bacteroides forsythus (25.0%), Wolinella spp. (33.3%) and Actinobacillus actinomycetemcomitans (50.0%) were similar in these sites compared with periodontitis sites. Morphologically distinct isolates, from 19 individuals positive for A. actinomycetemcomitans, were serotyped by indirect immunofluorescence.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1494450 TI - Relationship between oral gram-negative anaerobic bacteria in saliva of the mother and the colonization of her edentulous infant. AB - Various gram-negative anaerobic bacterial species can be detected in the oral flora of edentulous infants. However, knowledge of the initial infection source is still scarce. Thirty Caucasian mothers (mean age 30 years) and their edentulous infants (mean age 3 months) were examined for the possible similarity of the oral gram-negative anaerobic flora. Paraffin-stimulated saliva was collected from the mothers. A pooled swab sample from mucosal surfaces and unstimulated saliva were collected from the infants. The samples were inoculated on nonselective and selective media and cultured aerobically and anaerobically. All of the 30 mothers harbored Fusobacterium nucleatum and 29 mothers Prevotella melaninogenica in their saliva. The salivary levels of P. melaninogenica, F. nucleatum, nonpigmented Prevotella spp., Prevotella intermedia and Prevotella loescheii exceeded 10(4) CFU/ml in about half of the 30 mothers. At this maternal salivary level, the infants' colonization frequency of P. melaninogenica and F. nucleatum was doubled. A positive correlation between maternal salivary concentration and infant's colonization was found for P. melaninogenica. No positive association was found with nonpigmented Prevotella spp., P. intermedia and P. loescheii. It can be speculated that maternal saliva may act as a source of some gram-negative anaerobes in the oral microflora of edentulous infants as early as before tooth eruption. PMID- 1494451 TI - Frequency and stability of mono- or poly-infection by Actinobacillus actinomycetemcomitans serotypes a, b, c, d or e. AB - The aims of the study were to determine the prevalence of simultaneously multiple Actinobacillus actinomycetemcomitans serotypes in one individual, stability of infection by the same serotype and the occurrence of previously not described serotypes of A. actinomycetemcomitans. The serotypes of 515 clinical isolates of A. actinomycetemcomitans from 91 Finnish, Caucasian subjects, including 321 follow-up samples from 51 subjects, were determined with immunodiffusion assay. Most subjects (n = 86, 95%) were infected with one serotype only; 466 (91%) isolates from 80 subjects belonged to serotype a (25% of isolates/25 subjects), b (25% of isolates/27 subjects) or c (41% of isolates/30 subjects). Fifteen isolates from 4 subjects reacted with the antiserum raised against previously untypable clinical strain IDH 781 (serotype d) and 18 isolates from 5 subjects with the antiserum raised against strain IDH 1705 or IDH 3096 (serotype e). Sixteen (3%) isolates from 5 subjects remained untypable. The same infecting A. actinomycetemcomitans serotype(s) persisted for the 1-6 years of follow-up. In conclusion, the study indicates a rare simultaneous occurrence of multiple oral A. actinomycetemcomitans serotypes, the stability of infection by the same serotype(s) and the existence of serotypes of A. actinomycetemcomitans not previously described. PMID- 1494452 TI - Coaggregation studies of the Eubacterium species. AB - Eubacterium species are gram-positive anaerobic rods that are frequently isolated from subgingival plaque of periodontal pockets. Five Eubacterium species were tested for their ability to coaggregate with 33 oral bacterial strains. Using visual and turbidimetric assays, coaggregation was observed among Eubacterium brachy, Eubacterium nodatum, Eubacterium alactolyticum and Eubacterium limosum strains only when tested with Fusobacterium nucleatum strains; Eubacterium saburreum displayed only weak coaggregation ability. Coaggregation between F. nucleatum and the Eubacterium species was observed over a wide range of concentrations of each organism. The F. nucleatum strains contained a heat labile and the Eubacterium species a heat stabile coaggregation receptor. Arginine, histidine, lysine and glycine inhibited the coaggregation between F. nucleatum and the Eubacterium species. Sugars and other amino acids tested did not inhibit the observed coaggregation. Rabbit anti-F. nucleatum serum completely inhibited coaggregation, but anti-E. brachy serum and normal rabbit serum did not. As these anaerobic microorganisms are frequently isolated from the same oral lesions, the surface interactions observed may be important in the pathogenesis of these polymicrobic infections. PMID- 1494453 TI - Characterization of shared antigens of Fusobacterium nucleatum and Fusobacterium necrophorum. AB - Fusobacterium nucleatum and Fusobacterium necrophorum are gram-negative, non spore-forming anaerobic rods, frequently isolated from the normal flora and diseased lesions of the human oral cavity, gastrointestinal and genitourinary tracts. F. necrophorum is also known to be an animal pathogen. Studies were undertaken with rabbit anti-F. nucleatum sera and with human adult periodontitis (AP) sera that demonstrated the sharing of antigens between the two species. Immunodiffusion and immunoelectrophoresis studies of Fusobacterium species with rabbit anti-F. nucleatum sera demonstrated the presence of shared antigen(s) between F. nucleatum and F. necrophorum. Adsorption studies of AP sera in an enzyme-linked immunosorbent assay demonstrated the presence of antibodies reacting with the shared antigens of the two species. Immunoblot (IB) analysis of a soluble protein preparation of the two species of Fusobacterium, when allowed to react with rabbit anti-F. nucleatum 10197 serum, demonstrated 53 kDa and 30 kDa bands present in members of the two species. Further, IB analysis of protein preparations of the two species with AP sera indicated the presence of antibodies reacting with the shared 53 kDa band and in some cases the 30 kDa band. During serological testing with antisera or host immune studies with human sera to these species, the presence of shared antigens must be considered. PMID- 1494455 TI - Acid production by streptococci growing at low pH in a chemostat under anaerobic conditions. AB - Streptococcus mutans and other oral streptococci were grown in continuous culture under strictly anaerobic conditions. When the cultural pH was kept at 7.0, the main acid products were formate and acetate, as reported previously. However, more lactate was produced at pH values of 5.5 or 6.0, with a concomitant decrease in formate and acetate production. This change in fermentation products could partly be ascribed to a change in intracellular pH and difference in the pH optima between pyruvate formate-lyase (PFL) and lactate dehydrogenase (LDH). At extracellular pH values of 7.0 and 5.5, the intracellular pH values of S. mutans NCIB 11723 were 7.5 and 6.6, respectively. The pH optima of PFL and LDH were 7.8 and 5.5-6.3, respectively. The cells had also a larger amount of LDH during growth at pH 5.5 than at pH 7.0. PMID- 1494454 TI - The breakdown and utilization of peptides by strains of Fusobacterium nucleatum. AB - It has been claimed that most strains of Fusobacterium nucleatum require peptides rather than free amino acids for growth. In contrast, we have shown that, under continuous culture conditions, all strains tested grow in a chemically defined medium (CDM). The purposes of this study were to determine whether resting cells of F. nucleatum could attack unsubstituted peptides and whether growing cells could utilize a peptide fraction prepared from a commercial peptone. Resting cells cleaved all 19 peptides, containing 3-6 residues, and the 4 key energy yielding amino acids--Glu, His, Ser and Lys--were rapidly taken up. A hydrophilic Casitone fraction, rich in Glu, promoted growth and peptides < 1 kDa were rapidly utilized. The cleaved residues metabolized were those previously shown to limit growth in CDM: Glu, Ser, His and Lys. The endopeptidase activities of Porphyromonas gingivalis would provide the necessary peptides for the growth of F. nucleatum, which may partly explain why these two organisms frequently coexist in periodontally diseased sites. PMID- 1494456 TI - Reduced nicotinamide adenine dinucleotide oxidase involvement in defense against oxygen toxicity of Streptococcus mutans. AB - The growth inhibition of the Streptococcus mutans group, including Streptococcus mutans, Streptococcus cricetus, Streptococcus rattus and Streptococcus sobrinus, on glucose by oxygen and the properties of reduced nicotinamide adenine dinucleotide (NADH) oxidase induced by oxygen, using a representative oxygen tolerant strain, were examined. The growth response to oxygen varied among strains and correlated with the level of NADH oxidase activity in the cell extract. The induced synthesis of NADH oxidase as well as superoxide dismutase was affected by oxygen tension and energy sources. The induced NADH oxidase involved at least two types, major H2O-forming NADH oxidase and minor H2O2 forming NADH oxidase activity. In the presence of a scavenger of H2O2, pyruvate, the growth inhibition by oxygen in an oxygen-sensitive strain (GS5) was protected but not in another oxygen-sensitive strain (MT8148). The high level of induced H2O-forming NADH oxidase activity protected against oxygen toxicity. PMID- 1494458 TI - Feminism, relativism, and the philosophy of science: an overview. PMID- 1494457 TI - Inhibition of Candida albicans by the Peroxidase/SCN-/H2O2 system. AB - Effects of the salivary peroxidase (SPO) system on the growth, glucose uptake and metabolic activities of oral bacteria are well documented but the effects on oral fungi are virtually unknown. Therefore, the viability of Candida albicans (ATCC 28366) exposed to the peroxidase/SCN-/H2O2 system was studied in sterilized saliva, in phosphate-buffered saline (PBS) and in potassium chloride. The growth of C. albicans in glucose-supplemented saliva was faster at pH 5.5 than at pH 7. The addition of the complete SPO (or lactoperoxidase) system to either sterilized saliva, KCl (50 microM) or PBS at pH 5.5 inhibited dose-dependently the viability of C. albicans in KCl, but no inhibition was found in PBS or saliva. Maximal inhibition was achieved in 2 h and with > 320 microM of peroxidase-generated HOSCN/OSCN-. However, physiological salivary concentrations of phosphate (> or = 1.0 mM) and PBS blocked the antifungal effect of HOSCN/OSCN-. The relative proportions of SCN- and H2O2 were critical to the antifungal effects. With 0.2 mM KSCN, a complete loss of viability was achieved, though the HOSCN/OSCN- concentrations did not exceed 100 microM. It is concluded that C. albicans is sensitive to HOSCN/OSCN- but salivary concentrations of phosphate block the antifungal effect of the peroxidase systems. PMID- 1494459 TI - Is woman born or made? Female gender identity and women's health. PMID- 1494460 TI - Language and the reification of nursing care. PMID- 1494461 TI - The drive for professionalism in nursing: a reflection of classism and racism. PMID- 1494462 TI - A critical analysis of professionalism in nursing. PMID- 1494463 TI - Perceptions and feelings of nurses about horizontal violence as an expression of oppressed group behavior. PMID- 1494464 TI - Identity politics, essentialism, and constructions of "home" in nursing. PMID- 1494465 TI - Race, racism, and health: examining the "natural" facts. PMID- 1494466 TI - Eve's legacy: an analysis of family caregiving from a feminist perspective. PMID- 1494467 TI - A feminist critique of Jean Watson's theory of caring. PMID- 1494468 TI - Being there: who do you bring to practice? PMID- 1494469 TI - Evaluation research within the human caring framework. PMID- 1494470 TI - The impact of nurse caring on patient outcomes. PMID- 1494471 TI - The experience of caring in the acute care setting: patient and nurse perspectives. PMID- 1494472 TI - Trust as a caring construct with the critically ill: a beginning exploration. PMID- 1494473 TI - Mothers and drugs: two possibilities for caring. PMID- 1494474 TI - Caring: being manifested as ordinariness in nursing. PMID- 1494475 TI - Nursing: the caring practice "being there". PMID- 1494476 TI - The process of inflicting pain in nursing: caring relationship or torture? PMID- 1494477 TI - A caring presence: Confederate nursing practice. PMID- 1494478 TI - The historical conflict between caring and professionalization: a dilemma for nursing. PMID- 1494479 TI - Exploring the aesthetic meaning of presence in nursing practice. PMID- 1494480 TI - The magic of caring. PMID- 1494481 TI - The spiritual connection: nurses' perceptions of the experience of caring. PMID- 1494482 TI - Being there: an analysis of the concept of presence. PMID- 1494483 TI - The caring nursing environment. PMID- 1494484 TI - Reflections on the promotion of caring with head nurses. PMID- 1494485 TI - Characterization of two platelet aggregation inhibitor-like polypeptides from viper venom. AB - Two polypeptides, eristocophins I and II, have been characterized from leaf-nosed viper (Eristocophis macmahoni) venom. They contain 10 half-Cys residues of a total of 61/62 residues, have 72% residue identity, and exhibit similarities to platelet aggregation inhibitors and segments of adhesive proteins. Eristocophin I contains the sequence Arg-Gly-Asp, known to inhibit fibrinogen interaction with the platelet receptor. Eristocophin II has Met instead of Arg in this sequence, and an adjacent Trp-Asn-Asp segment. The latter is also typical of adhesive proteins, thus linking two potentially functional segments in one molecule. Exchanges are maximal in these segments, suggesting that the polypeptides exhibit functional divergence with isoform differences in important regions. PMID- 1494486 TI - Isolation and quantitation of several new peptides from the canine neurotensin/neuromedin N precursor. AB - Using antisera towards the bioactive peptides, neurotensin and neuromedin N, as well as towards the N-terminal and C-terminal regions of their shared 170-residue precursor, peptides representing various portions of the precursor were isolated from extracts of canine ileum. In total, seven peptides were isolated, two of which had not been previously identified. One was the C-terminal tail of the precursor (Gly-Ser-Tyr-Tyr-Tyr) and the other was the tail peptide extended N terminally to include neurotensin (Glp-Leu-Tyr-Glu-Asn-Lys-Pro-Arg-Arg-Pro-Tyr Ile-Leu-Lys-Arg-Gly-Ser-Tyr -Tyr- Tyr). By comparing the measured concentrations for each of the identified peptides, it was established that processing at the three Lys-Arg cleavage sites within the precursor did not occur to the same extent. Cleavage at the N-terminus of neuromedin N was approximately 10% complete, that between neurotensin and the tail was approximately 90% complete, and that between neuromedin N and neurotensin was approximately 95% complete. Three immunoreactive proteins were also identified by immunochemical and chromatographic analyses: N-terminally extended neuromedin N (125 residues), N terminally extended neurotensin (140 residues), and the entire 147-residue precursor. It was concluded that neurotensin, tail and large molecular neuromedin N were the primary products of processing for this precursor in canine ileum, while minor products included neuromedin N, neurotensin tail, and large molecular neurotensin. PMID- 1494487 TI - A sensitive and specific two-site, sandwich-amplified enzyme immunoassay for neuropeptide Y. AB - The development of a new enzyme immunoassay for neuropeptide Y (NPY) is reported. Two monoclonal antibodies directed against distinct epitopes of NPY are used, one as a capture antibody (NPY02) and the other one as an indicator antibody (NPY05), this latter antibody being labeled with alkaline phosphatase. The assay calibration curve was performed over concentrations of 1 to 250 pM in a NPY-free plasma. The intra-assay coefficient of variation (CV) ranged from 0.025 to 11.9%, whereas the interassay CV was comprised between 5 and 12%. The limit of detection of this assay was 1 pM (100 amol/well). Neuropeptide Y levels are related to sampling conditions; basal concentrations of NPY with low SEM are found when less than 1.2 ml of blood is taken in EDTA tubes, the sample is centrifuged at 4 degrees C, and immediately frozen. Unanesthetized spontaneously hypertensive rats exhibited higher NPY plasma concentrations than normotensive Wistar-Kyoto controls (53 +/- 7 pM and 25 +/- 2 pM, respectively, mean +/- SEM, p < 0.01). Plasma NPY levels are similar in 16- and 36-week-old animals. In conclusion, this technique makes it possible to assay a large number of samples within 24 h without requiring radioactivity. PMID- 1494488 TI - Effects of thermal peptides on retention of footshock avoidance training in mice. AB - Some hydrophobic polypeptides known as thermal proteins have been found to have neurotrophic effects. Thermal proteins were synthesized from aspartic acid, glutamic acid, proline, and tryptophan. Two hydrophobic and one nonhydrophobic polymers were injected intracerebroventricularly into brains of mice after partial training on footshock avoidance run in a T-maze. When retention was tested 1 week later, the hydrophobic polymers enhanced retention while the nonhydrophobic polymer did not. Thermal proteins exhibiting hydrophobicity and having neurotrophic effects may aid in altering synaptic connections by facilitating cell recognition. PMID- 1494489 TI - Oxytocin in obsessive compulsive disorder. AB - A double-blind, placebo-controlled study with syntocinon (oxytocin) was carried out in 12 patients, nine females and three males with obsessive compulsive disorder (OCD). Patients were treated by intranasal administration of oxytocin spray (18 IU per day) or placebo. No reductions in the number of obsessions or compulsive behaviors were observed in either treatment group. To evaluate whether a higher dosage would exert more beneficial effects, two additional patients were treated with a threefold higher dosage of oxytocin using an open design. In one patient a slight reduction in the number of checking rituals was observed, whereas in the other patient virtually no effect was observed. The results of this study do not support the hypothesis that oxytocin might be a potential anticompulsive agent. PMID- 1494490 TI - Calcium-dependent pro-cholecystokinin V-9-M immunoreactive peptide release from rat brain slices and CCK-secreting rat medullary thyroid carcinoma cells in culture. AB - The release of peptides immunoreactive for a synthetic peptide (V-9-M) contained in the amino-terminal of pro-CCK was examined. The potassium-evoked release of V 9-M immunoreactive peptides from rat cerebral cortical slices in vitro was calcium dependent. Cholecystokinin-secreting rat medullary thyroid carcinoma cells also secreted significant quantities of these peptides. Sephadex column chromatography of the release media from slices and cells showed two V-9-M immunoreactive peptides, one larger and one smaller than V-9-M itself. Previous behavioral studies have suggested that V-9-M has a distinct neuropharmacological profile. These results demonstrate that V-9-M-like peptides are released along with CCK-8 and are consistent with the hypothesis that V-9-M-like peptides may be neurotransmitters or neuromodulators or may be involved in the sorting or transport of CCK-8. PMID- 1494491 TI - The role of cholecystokinin (CCK8) on glucose production and elimination, and on plasma insulin and glucose in rats. AB - The effects of the gastrointestinal hormone and neurotransmitter cholecystokinin (CCK8) are complex, since it exhibits both an insulinotropic and a glucagonotropic effect. We investigated CCK8 in vivo with respect to glucose fluxes (production and elimination) at both low (6 mM) and high plasma glucose levels (9 mM) using the primed constant D-[3-3H]glucose infusion technique. In the presence of high glucose levels there was a dose-dependent increase in glucose elimination by CCK8. No effect of CCK8 on glucose production at a high glucose infusion rate (500 mg/kg per h) was observed in contrast to a low glucose infusion rate (100 mg/kg per h); plasma glucagon levels were elevated. All effects on glucose production and elimination were specific, since they were abolished by the CCK receptor antagonist L-364,718. In summary, glucose elimination was slightly increased by CCK8 at low glucose levels but increased to a greater extent at high glucose levels; glucose production was increased by CCK8 only at low glucose levels. Thus, CCK is a regulator of glucose homeostasis. PMID- 1494492 TI - Peripheral insulin administration attenuates the increase in neuropeptide Y concentrations in the hypothalamic arcuate nucleus of fasted rats. AB - Fasting increases neuropeptide Y (NPY) concentrations in the arcuate nucleus (ARC), its site of synthesis, and in other regions of the rat hypothalamus. Neuropeptide Y is a potent central orexigenic agent and may therefore stimulate appetite during fasting. We tested the hypothesis that low plasma insulin levels stimulate ARC levels of NPY in fasted rats. Compared with freely fed controls (n = 8), rats fasted for 72 h (n = 8) showed significantly lower plasma insulin levels (28.9 +/- 1.6 vs. 52.6 +/- 5.7 pmol/l; p < 0.001) and higher ARC NPY concentrations (14.2 +/- 1.8 vs. 8.4 +/- 2.2 fmol/micrograms protein; p < 0.001). Fasted rats treated with subcutaneous insulin (5 U/kg/day; n = 10), which nearly normalized plasma insulin (46.6 +/- 2.8 pmol/l), showed intermediate ARC NPY levels (11.2 +/- 1.4 fmol/micrograms protein; p < 0.01 vs. controls and untreated fasted rats). Insulin administered peripherally, therefore, attenuates fasting induced NPY increases in the ARC, supporting the hypothesis that hypoinsulinemia stimulates hypothalamic NPY. PMID- 1494493 TI - D-amino acid and alanine scans of the bioactive portion of porcine motilin. AB - A recent systematic study of porcine motilin fragments has clearly shown that biological activity resides in the amino-terminal end. The amino-terminal tetradecapeptide retains more than 90% of the potency of the full molecule. We now examined the effect of replacement of residues 1 through 11 by either their D isomer or by alanine in [Leu13]pMOT(1-14). Peptides were synthesized using Fmoc solid phase methodology, purified by HPLC, and assayed for their ability to displace bound motilin (rabbit antral smooth muscle homogenate) and to induce contractions (isolated rabbit duodenal segments). The negative logarithm of the concentration displacing 50% of the tracer (pIC50), or producing 50% of the maximal contractile response (pEC50), was determined. All compounds were still full agonists. A reduction in potency of more than two log units was seen for the compounds in which residues 1 (Phe), 4 (Ile), and 7 (Tyr) were replaced by Ala and residues 3 (Pro), 4 (Ile), and 6 (Thr) by their D-isomer. The largest drop was noted for the analogs substituted at position 4. For all compounds there was an almost perfect correlation between the pIC50 and the pEC50 values (r = 0.96), although the pEC50 was consistently smaller. These results show that the biological activity of motilin is mainly determined by the first seven residues. The pharmacophore consists of the aromatic rings from Phe1 and Tyr7 and the aliphatic side chains from Val2 and Ile4. Pro3, Phe5, and Thr6 may stabilize the bioactive conformation. PMID- 1494494 TI - Large and prolonged in vivo response of pancreatic secretion to phenylethylamide and phenylethylester derivatives of Boc-[Nle28-Nle31]CCK(26-33) in the rat. AB - Supramaximal doses of cholecystokinin (CCK) induce in vitro submaximal biological responses (i.e., smaller by 50% than the response to a maximal dose of CCK), desensitization and residual stimulation, and in vivo secretory inhibition and edematous pancreatitis. It has been reported previously that supramaximal doses of Boc-[Nle28-Nle31]CCK(27-32)/- phenylethylester (JMV 180) do not produce these effects. The aim of this study was to analyze the in vivo response of pancreatic secretion of the rat to a wide dose range of Boc-[Nle28-Nle31]CCK(26-33) (JMV118), an analog of CCK8 with the same activity spectrum as CCK8, to JMV180 and to Boc-[Nle28-Nle31]CCK(27-32)-phenylethylamide (JMV170). The three peptides were administered as intravenous infusions and as bolus intravenous injections. In the case of infusions, the same maximal effect was observed with all three peptides. It was obtained with 22.5 pmol/kg.min of JMV118; JMV180 and JMV170 were about 700 times less potent. In the case of bolus injections, the maximal response to JMV118 was observed with 450 pmol/kg, and the response peaked 10-15 min after the injection. Higher doses of JMV118 induced a secretory peak that was smaller and delayed relative to the moment of injection. JMV180 and JMV170 were about 500 times less potent: the maximal response was observed with 218700 pmol/kg and peaked 10-15 min after the injection. Larger doses of JMV180 and JMV170 produced neither supramaximal inhibition nor a delayed peak response, but induced a sustained stimulation of pancreatic secretion that could last more than 3 h after the injection.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1494495 TI - Pituitary adenylate cyclase activating polypeptide (PACAP) reduces food intake in mice. AB - Pituitary adenylate cyclase activating peptide (PACAP) is a peptide that is present in the hypothalamus and other areas of the rat brain. This study demonstrates that PACAP reduces food intake after intracerebroventricular injection in food-deprived mice. Behavioral analysis suggests that this decrease in food intake is, in part, compensated for by an increase in other behaviors. Pituitary adenylate cyclase activating peptide also was demonstrated to antagonize increased food intake resulting from administration of neuropeptide Y. Thus, PACAP joins a growing list of neuropeptides involved in the central regulation of food intake. PMID- 1494496 TI - The effect of N-terminal substitutions on the biological activity of MSH fragments. AB - In order to study the role of N-terminal substitutions of peptide sequences related to the active site of alpha-melanotropin, [Glp5]alpha-MSH(5-10), [Glp5,D Phe7]alpha-MSH(5-10), [Sar5,D-Phe7]alpha-MSH(5-10), [Nle4,D-Phe7]alpha-MSH(4-10), [N-carbamoyl]alpha-MSH(5-10), and formyl and acetyl derivatives of alpha-MSH(5 10), [Gly5]alpha-MSH(5-10) and [Gly5,D-Phe7]alpha-MSH(5-10), were synthesized in solution. The N-terminal acylations enhance by 2 to 10 times the melanin dispersing activity of the unsubstituted sequences. Alkylation of the N-terminus does not change the biological activity of the parent peptide, suggesting the necessity of a carbonyl group for increasing the hormonal effect. PMID- 1494497 TI - The effect of corticotropin-releasing factor (CRF) on autonomic and behavioral responses during shock-prod burying test in rats. AB - When administered intracerebroventricularly (ICV) in rats, corticotropin releasing factor (CRF) possesses arousing and anxiogenic properties, which may be found reflected in autonomic and behavioral activation. As these responses are dependent on dose and situation, ICV-injected CRF may affect behavioral responses to a defined stimulus in a different fashion than autonomic concomitants. Two experiments were conducted in order to test this hypothesis. In both experiments, rats were treated ICV with CRF or an artificial cerebrospinal fluid (aCSF) 5 min prior to a 15-min exposure to an electrified prod (shock-prod burying test, SPB test) in their home cages. In the first experiment, 0.3 ng CRF injected ICV in unhandled rats significantly reduced the prod-burying response to electric shock, in favor of immobility, whereas following 300 ng CRF ICV, the predominant behavioral response was grooming behavior. In contrast, habituated rats, implanted with telemetric devices to measure heart rate, core temperature, and gross activity in the second experiment, showed a significant increase of burying behavior after 0.3 ng CRF ICV, in comparison to vehicle-treated controls. However, simultaneous cardiac acceleration was of the same magnitude and duration in both groups. In addition, whereas similar rises in CT were observed in both groups during the SPB test, CRF-treated rats showed more marked rise in core temperature during the first 15 min of the posttest period. At the 24-h retention test, rats belonging to the CRF group showed burying behavior and HR responses, in onset, magnitude, and duration similar to day 1, whereas extinction of the burying response and tachycardia was found in controls. Changes in CT, although less marked, showed the same pattern as on day 1 in both groups. These results show a differential effect of central CRF on behavioral and autonomic activation induced by a well-defined stressful stimulus. The response to CRF seems to be not only situation related, but also dependent on the pretest experience of the animal. PMID- 1494498 TI - Rainbow trout (Oncorhynchus mykiss) neuropeptide Y. AB - Neuropeptide Y (NPY) has been isolated from brain extracts of the rainbow trout (Oncorhynchus mykiss) and subjected to structural analyses. Plasma desorption mass spectroscopy estimated the molecular mass of the purified peptide as 4303.9 Da. Automated Edman degradation unequivocally established the sequence of a 36 amino acid residue peptide as: Tyr-Pro-Pro-Lys-Pro-Glu-Asn-Pro-Gly-Glu-Asp-Ala Pro-Pro-Glu-Glu-Leu-Ala- Lys- Tyr-Tyr-Thr-Ala-Leu-Arg-His-Tyr-Ile-Asn-Leu-Ile-Thr Arg-Gln-Arg-Tyr. The molecular mass calculated from this sequence (4304 Da) is consistent with that obtained by mass spectroscopy. The presence of a C-terminal amide was established by radioimmunoassay. Rainbow trout NPY is identical in primary structure to coho salmon (Oncorhynchus kisutch) pancreatic polypeptide (PP). These data may indicate that, in this group of salmonid fishes, a single member of the NPY/PP peptide family is expressed in both neurons and peripheral endocrine cells. PMID- 1494499 TI - Microvascular effects of atrial natriuretic peptide in rat cremaster. AB - Experiments utilized the open cremaster preparation to test the hypothesis that atrial natriuretic peptide (ANP)-induced volume changes result from microvascular resistance alterations. Atrial natriuretic peptide (25, 100, and 500 ng/kg/min, IV) or vehicle was infused into anesthetized rats. At the two highest ANP infusion rates, mean arterial pressure was significantly reduced from 104 +/- 3 (control) to 87 +/- 2 and 77 +/- 2 mmHg, respectively. Hematocrit was 41.0 +/- 0.8 and 45.6 +/- 0.9% (p < 0.05) at the end of vehicle and ANP infusions, respectively. Despite these effects of ANP, there were no significant arteriolar or venular diameter alterations. Thirty microM nitroprusside significantly dilated all vessel segments except large venules. These observations suggest that resistance alterations in the skeletal muscle microvasculature are not the cause of ANP-induced fluid movement. PMID- 1494500 TI - Decreased behavioral effects of daily intracerebroventricular bombesin. AB - Intracerebroventricular (ICV) bombesin increases grooming and decreases food intake in rats. We examined tolerance to these effects by administering a daily injection of either saline or 25 ng bombesin to rats for 8 days via lateral ventricular cannulas. Food intake and grooming were monitored. After 8 days bombesin no longer increased grooming or decreased food intake in bombesin treated rats, but did increase grooming and decrease food intake in saline treated rats. This development of behavioral tolerance conflicts with previous reports using larger doses and demonstrates that repeated small doses of ICV bombesin produce different effects from larger doses. PMID- 1494502 TI - Immunosuppressive activity of antamanide and some of its analogues. AB - In connection with our discovery of a strong immunosuppressive activity of cyclolinopeptide A (CLA), we investigated immunosuppressive properties of antamanide and a number of its analogues, including symmetrical antamanide, and compared them with the activities of cyclosporin A and CLA. The peptides were investigated by using plaque forming cell (PFC), graft-versus-host (GvH), delayed type hypersensitivity (DTH), and autologous rosette formation cell (ARFC) tests. Antamanide and symmetrical antamanide exhibit an immunosuppressive activity lower than CLA. Linear antamanide fragments are also active. At higher concentrations of the latter peptides, toxic effects occur. PMID- 1494501 TI - Characterization of endozepine-related peptides in the central nervous system and in peripheral tissues of the rat. AB - Endozepines represent a novel family of regulatory peptides that have been isolated by their ability to displace benzodiazepines from their binding sites. All endozepines derive from an 86 amino acid precursor polypeptide called diazepam binding inhibitor (DBI), which generates, through proteolytic cleavage, several biologically active endozepines. The aim of the present study was to compare the molecular forms of endozepines present in different regions of the rat brain and in various peripheral organs using an antiserum raised against the central (biologically active) region of DBI. Combination of HPLC analysis and RIA detection revealed the existence of two major forms (peaks I and II) of endozepine-immunoreactive peptides. The retention times of the two peaks (36 and 39 min, respectively) were identical in all tissues or organs tested. Western blotting analysis of cerebral cortex extracts confirmed the existence of two immunoreactive species with apparent molecular weights 4000 and 6000 Da, which respectively correspond to peaks I and II. Tryptic digestion of peaks I and II generated a single immunoreactive peptide that coeluted with the synthetic octadecaneuropeptide ODN [DBI(33-50)]. These results show that, in different parts of the brain and in various peripheral organs, DBI is rapidly processed to generate two peptides of apparent molecular weight of 4000 and 6000 Da, which both possess the biologically active determinant of endozepines. PMID- 1494503 TI - CGRP immunoreactivity and NADPH-diaphorase in afferent nerves of the rat penis. AB - Calcitonin gene-related peptide (CGRP)-immunoreactive afferent nerve fibers are abundant in the rat penis. In addition, NADPH-diaphorase, which stains for nitric oxide synthase, has been localized within both autonomic and sensory dorsal root ganglia (DRG) and may be part of an important biochemical pathway involved in penile tumescence. The purpose of this study was: 1) to examine the circuitry of afferent nerves that are CGRP immunoreactive from the L6 DRG, 2) to examine the possibility that there are NADPH-diaphorase-positive afferent fibers from the L6 DRG to the rat penis, and 3) to examine the localization and colocalization of CGRP and NADPH-diaphorase within L6 DRG afferent perikarya. Calcitonin gene related peptide immunostaining in the penis was eliminated following a bilateral transection of the pudendal nerves, but was unchanged following a bilateral transection of the pelvic splanchnic or hypogastric nerves. The NADPH-diaphorase staining was not altered by any of the nerve transections. Injection of the retrograde axonal tracer fluorogold (FG) into the dorsum penis labeled perikarya in the L6 DRG. Although the majority of FG-labeled perikarya contained neither CGRP nor NADPH-diaphorase, small subpopulations of perikarya contained either CGRP immunoreactivity, NADPH-diaphorase, or both. A unilateral pudendal nerve transection virtually eliminated (> 99%) FG labeling in the ipsilateral L6 DRG. These data suggest that NADPH-diaphorase and CGRP are present, either together or separately, within a subpopulation of penile afferent perikarya. In addition, CGRP-immunoreactive afferent nerve fibers reach the penis primarily via the pudendal nerves. Finally, NADPH-diaphorase-positive penile afferents may be another important source of nitric oxide (NO) for penile tumescence. PMID- 1494505 TI - Permeability of the blood-brain barrier to peptides: an approach to the development of therapeutically useful analogs. AB - Peptides have been shown in both in vivo and in vitro systems to cross the blood brain barrier (BBB) and so affect function on the side contralateral to their origin. Some peptides cross primarily by transmembrane diffusion, a nonsaturable mechanism largely dependent on the lipid solubility of the peptide. Other peptides are transported by saturable systems across the BBB. These transport systems can be in the CNS to blood direction, as in the cases of Tyr-MIF-1 and methionine enkephalin, in the blood to CNS direction, as in the case of peptide T, or bidirectional, as in the case of LHRH. Other factors that also affect the amount of peptide crossing the BBB include binding in blood, volume of distribution, enzymatic resistance, and half-time disappearance from the blood. An in vitro model of the BBB has been characterized and used to confirm that peptides can cross the BBB. Results with the model agree with those obtained in vivo and have been used to study the permeability of the BBB to peptides, the effect of peptides on BBB integrity, the cellular pathway peptides and proteins use to cross the BBB, and the ability of the BBB to degrade peptides. The in vivo and in vitro methods have been used together to develop halogenated enkephalin analogs that are enzymatically resistant, cross the BBB readily to accumulate in areas of the brain rich in opiate receptors, and are powerful analgesics.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1494504 TI - Endogenous opiates: 1991. AB - This paper is the fourteenth installment of our annual review of research concerning the opiate system. It includes papers published during 1991 involving the behavioral, nonanalgesic, effects of the endogenous opiate peptides. The specific topics this year include stress; tolerance and dependence; eating; drinking; gastrointestinal and renal function; mental illness and mood; learning, memory, and reward; cardiovascular responses; respiration and thermoregulation; seizures and other neurological disorders; electrical-related activity; general activity and locomotion; sex, pregnancy, and development; immunological responses; and other behaviors. PMID- 1494506 TI - Management of hydatid disease of the liver. PMID- 1494508 TI - Pyrexia of unknown origin: changing spectrum of diseases in two consecutive series. AB - Comparison was made of the aetiology and methods of diagnosis in two series of patients meeting the classic criteria of pyrexia of unknown origin during 1968 1981 and during 1982-1989 seen in the Department of Internal Medicine at La Paz University Hospital, Madrid, Spain. There was a statistically significant decrease in the percentage of infections and an increase in neoplasms and connective tissue disorders in the second series. The percentage of patients diagnosed by laparatomy was similar in both series but the diagnosis yield at laparotomy was greater in the second period. Pyrexia of unknown origin continues to be a condition which can defy clinical expertise in in spite of advances in diagnostic techniques. PMID- 1494507 TI - An update on nitrate tolerance: can it be avoided? PMID- 1494509 TI - The effect of hemiplegia on blood pressure measurement in the elderly. AB - The blood pressure in both arms of 103 unselected hemiplegic patients was measured using a random-zero sphygmomanometer. Although for the whole sample the mean blood pressure in the paretic and unaffected arm was similar, a significant difference was found when the patients were subdivided according to the tone of the arm. The blood pressure was higher in paretic arms of patients with a spastic stroke and lower in the affected arm if the tone was flaccid. No other characteristics were associated with significant blood pressure differences, so that the findings appear to be directly related to changes in muscle tone. After a stroke the blood pressure should always be measured in the unaffected arm because changes in tone make measurements unreliable. PMID- 1494510 TI - Mycobacteria as a cause of infective exacerbation in bronchiectasis. AB - In 91 patients with bronchiectasis seen over 6 years, a positive mycobacterial culture was obtained in 12 cases (13%). The organisms isolated were Mycobacterium tuberculosis in nine cases, Mycobacterium avium in two cases and Mycobacterium tuberculosis and chelonei were obtained on separate occasions in one case. Computed tomography and/or bronchography showed that the bronchiectatic changes commonly involved the lower lobes and to a lesser extent, the middle and lingula lobes. In none of these 12 cases was tuberculosis strongly suspected on clinical or radiological grounds. We conclude that mycobacterial infections are common in patients with bronchiectasis and sputum should be cultured for mycobacteria periodically in these patients. In doubtful cases, bronchoscopy may be helpful to obtain a positive mycobacterial culture. PMID- 1494511 TI - The differing predictive values of oestrogen receptor assays for large breast cancers. AB - Thirty elderly patients with T3 or T4 breast cancer underwent a wedge biopsy for radioligand-binding assay (RLA) of oestrogen receptor (ER) activity. A second, separate group of 21 elderly patients with T3 and T4 breast cancers underwent fine needle aspiration biopsy (FNA) for immunocytochemical assay of ER (ER-ICA). All the women received tamoxifen as primary treatment and response was assessed by UICC criteria. Tumour ER concentration by RLA was correlated with both response (Spearman's R = + 0.52) and time to progression (R = + 0.76). Nine patients with receptor-rich tumours (> 100 fmol/mg protein) failed to show a response. However, the percentage of cells staining for ER by ER-ICA assay was much more strongly related to the likelihood of response (R = + 0.89); no patient with < 20% cells staining responded. Wedge biopsy and the biochemical determination of ER activity is of limited value in predicting the likely response to tamoxifen; ER-ICA assays on such tumours may be more informative. PMID- 1494512 TI - What are the benefits of routine breast cancer follow-up? AB - The value of follow-up after potentially curative treatment of breast cancer remains controversial. Recurrence-free women (n = 402) attending a breast clinic over a 3 month period were studied. The women attended 423 appointments, 412 of which were routine. Eleven were requested by the patient or general practitioner (interval appointments). All 11 interval and 19 of the routine appointments resulted in investigations for possible recurrence. Three (27%) interval appointments and four (1%) routine appointments resulted in the diagnosis of a recurrence (P < 10(-5). The attitudes of 285 patients to follow-up were investigated by questionnaire. Two hundred and twenty-three (78%) questionnaires were completed. Regular follow-up in the breast clinic was preferred to attendance only when symptomatic by 190 (85%) women and 169 (76%) preferred regular breast clinic visits to general practitioner follow-up. Most women (n = 174) (81%) said they felt reassured and less anxious having attended the breast clinic. Routine follow-up after potentially curative treatment of breast cancer is inefficient in the detection of recurrence. It is, however, highly rated for providing reassurance and reducing anxiety. Reassurance rather than detection of recurrence may be the most important function of the breast cancer follow-up clinic. PMID- 1494513 TI - Endogenous sex hormones and bone mineral density among community-based postmenopausal women. AB - In order to describe the relationships between endogenous sex hormones and bone mineral density in healthy postmenopausal women, we carried out a cross-sectional study of 90 community-based women, all at least one year since their last menstrual period (mean 9.6 +/- 4.9 years, range 1-22) and with a serum oestradiol level less than 100 pmol/l. None was currently using hormone replacement therapy. Serum oestradiol, testosterone, sex hormone binding globulin, dehydroepiandrosterone sulphate, and androstenedione were measured using standard techniques. Free oestradiol and testosterone indices were derived as the ratio of total hormone to sex hormone binding globulin, respectively. Total body, spine and hip bone mineral density (g/cm2) were measured by dual energy X-ray absorptiometry. Significant positive correlations were found between the free oestradiol and testosterone indices and bone mineral density at all sites. These relationships remained significant for the free oestradiol index after adjustment for age and body mass index. By stepwise multiple regression analysis, the free oestradiol index was an independent predictor of total body, spine and hip bone mineral density, accounting for 4-17% of the variance. These findings suggest an independent positive relationship between endogenous free oestradiol and total body, spine and hip bone mass even in the late postmenopause. PMID- 1494515 TI - Family therapy. AB - The discipline of family therapy, one of the psychotherapies, is defined and illustrated clinically in this article using case material. References are provided which allow further reading about family systems medicine. PMID- 1494514 TI - Crohn's disease in Bangladeshis and Europeans in Britain: an epidemiological comparison in Tower Hamlets. AB - The incidence of Crohn's disease in a defined Bangladeshi community was assessed in a retrospective, epidemiological study in the London Borough of Tower Hamlets from 1972 to 1989. The borough population of 164,000 includes over 28,000 Bangladeshis. Potential cases were identified from hospital pathology and medical records. There were 99 cases of Crohn's disease during the study period, of which five were Bangladeshi. The mean standardized incidence in Bangladeshis was 1.2/10(5)/year in the 1970s and 2.3/10(5)/year in the 1980s compared with 3.8/10(5)/year and 4.1/10(5)/year in Europeans, and 4.6/10(5)/year and 5.4/10(5)/year in West Indians, respectively. None of the changes with time was statistically significant. There were no cases amongst Hindus. The relative risk to Europeans, compared to Bangladeshis, was 2.5 during the 1970s and 2.0 in the 1980s. The difference between European incidence and that of other ethnic groups was not statistically significant; however, the number of Bangladeshi cases was small (five), and diminishes the power of the study. The apparent similarity of the incidences of Crohn's disease in Bangladeshis and Europeans contrasts with findings in other South Asians. Further investigations of the differences in incidence of Crohn's disease in South Asians is needed. PMID- 1494516 TI - Further evidence for differential regulation of follicle-stimulating hormone (FSH) and luteinizing hormone (LH): increased FSH and decreased LH levels in a patient with familial pure gonadal dysgenesis. AB - There is experimental evidence that a portion of follicle-stimulating hormone (FSH) secretion is independent of hypothalamic influences. A 29 year old woman with familial pure gonadal dysgenesis developed myelodysplastic syndrome. Endocrine investigations showed discrepancy between serum FSH and luteinizing hormone (LH) levels. FSH levels remained elevated while LH levels decreased. The FSH to LH ratio was 10 (normal 2-2.5). The fall in LH is likely to be due to factor(s) involved directly and specifically in LH synthesis and release. Exogenous LH releasing hormone administration as well as hormonal replacement treatment increased LH levels. The FSH to LH ratio decreased to 7. This case supports the hypothesis of differential regulation of FSH and LH, and that FSH secretion is at least partly autonomous. PMID- 1494517 TI - Splenic rupture following splenic vein thrombosis in a man with protein S deficiency. AB - We present a case of spontaneous splenic rupture in a man with splenic vein thrombosis. The splenic vein thrombosis appears to have been caused by protein S deficiency. We are not aware of this having been described before. PMID- 1494518 TI - Streptococcus bovis endocarditis as a presenting manifestation of idiopathic ulcerative colitis. AB - Streptococcus bovis bacteraemia and endocarditis have been associated with several gastrointestinal diseases, mainly malignant or potentially malignant tumours, and less commonly non-malignant gastrointestinal disorders. We describe a 73 year old man in whom Streptococcus bovis endocarditis developed, and was the presenting manifestation of undiagnosed quiescent ulcerative colitis. Such an association has not been described previously. PMID- 1494519 TI - Carnitine deficiency associated with long-term pivampicillin treatment: the effect of a replacement therapy regime. AB - A 51 year old female developed a skeletal muscle myopathy after 3 months of pivampicillin therapy. Pivampicillin can cause carnitine deficiency due to the pivalic acid side group. Plasma carnitine content and the patients symptoms failed to improve significantly on discontinuing the drug. Oral carnitine replacement therapy was administered for 6 weeks but the patient's plasma carnitine levels responded only slowly to this treatment. It is suggested that pivampicillin inhibits uptake of carnitine from the gut and may either directly or indirectly depress endogenous carnitine synthesis. In such cases a more aggressive carnitine replacement regime is indicated and pivampicillin should be avoided in patients requiring long-term antibiotic administration. PMID- 1494520 TI - Hepatic and pulmonary complications of herbal medicines. PMID- 1494521 TI - Addisonian crisis presenting with a normal short tetracosactrin stimulation test. PMID- 1494522 TI - Percutaneous endoscopic gastrostomy in elderly patients. PMID- 1494523 TI - The broken heart: noninvasive measurement of cardiac autonomic tone. PMID- 1494525 TI - Complications associated with percutaneous needle biopsy of the liver when one, two or three specimens are taken. AB - The diagnostic yield of blind percutaneous liver biopsy is improved when two or three specimens are taken during the procedure by redirecting the needle through a single entry-site, without exposing the patient to a greater risk of complications provided that standard precautions are taken. This study was designed to obtain further data on the safety of this procedure at King Edward VIII Hospital, Durban. During the period 1984-1990 (inclusive) a total of 2,646 biopsies were carried out: a single specimen was obtained in 834 patients, two specimens in 983 patients and three in 829 patients. Complications directly attributable to the procedure occurred in 24 patients who had one specimen, 20 who had two, and 19 who had three specimens taken during the biopsy. A single specimen had been obtained from three of the eight patients who had died, two specimens had been taken from another patient, and three specimens were obtained from the other four patients, i.e. patients in whom two or three specimens were taken did not have a higher incidence of pain, symptomatic hypotension, biliary peritonitis or death than those in whom one specimen was taken. Accordingly, when blind percutaneous needle biopsy of the liver is carried out, two specimens should be obtained by redirecting the needle through a single entry site as this improves the diagnostic yield without increasing complications. The morbidity and mortality associated with liver biopsy in this hospital is, however, high. Good technique, careful monitoring of patients after biopsy and prompt and aggressive resuscitation are essential if the mortality rate is to be reduced. PMID- 1494524 TI - Prediction of mortality in patients in acute medical wards using basic laboratory and anthropometric data. AB - The value of anthropometric and biochemical indices in predicting short-term mortality among patients in general medical wards was assessed in 294 patients admitted consecutively to a district hospital over a one month period. Using a stepwise logistic regression model and supported by the linear discriminant analysis method, mortality within 3 months could be predicted with sensitivity of 83% and specificity of 84% using the following variables: sex, functional ability, urea, total protein, alkaline phosphatase and albumin-adjusted calcium. Addition of anthropometric values and biochemical nutritional indices did little to improve the accuracy of the prediction, contrary to previous findings among surgical patients and elderly residents of long-term care institutions. PMID- 1494526 TI - Intratesticular epidermoid cyst. PMID- 1494527 TI - Late onset epilepsy in undiagnosed tuberous sclerosis. AB - A 67 year old woman first developed left-sided sensorimotor seizures postoperatively in association with infection and mild hyponatraemia. She was found to have previously unrecognized tuberous sclerosis, with gross pathognomic features: periungual fibromata, facial angiofibromata, calcified subependymal nodules, cortical tubers and multiple renal angiomyolipomata. Her son who was epileptic was also found to have other mild features of tuberous sclerosis as a result. As far as we are aware our patient is the oldest for the first presentation of tuberous sclerosis. PMID- 1494528 TI - Amoebic psoas and liver abscesses. AB - A 28 year old woman with a history of a dysenteric illness and documented Campylobacter infection presented with amoebic psoas and liver abscesses. A review of the literature of the last 20 years did not yield any reports of an amoebic psoas abscess. PMID- 1494529 TI - Strongyloides stercoralis hyperinfection in a patient with angioimmunoblastic lymphadenopathy. AB - A 29 year old Bengali male patient on chemotherapy for angioimmunoblastic lymphadenopathy developed Strongyloides hyperinfection syndrome 3 months after being treated with a single 3 day course of thiabendazole. His complicated hospitalization and successful management are described. Prevention of this potentially fatal disease in immunocompromised patients by early diagnosis and proper management of intestinal strongyloidiasis is emphasized. PMID- 1494531 TI - Is there a place for research in surgical training? PMID- 1494530 TI - Familial Conn's syndrome. AB - We describe the occurrence of primary hyperaldosteronism in two sisters. Although this is only the second published report of familial Conn's syndrome, it does have implications for the relatives of patients with Conn's syndrome and these are discussed. PMID- 1494532 TI - Attitudes of senior registrars in geriatric medicine to research. PMID- 1494533 TI - Fluid leak from an iliac crest in a biopsy site. PMID- 1494534 TI - Cholestatic jaundice associated with danazol therapy. PMID- 1494535 TI - Giant-cell arteritis of the ovarian arteries with associated temporal arteritis. PMID- 1494536 TI - Nocardia brasiliensis meningitis. PMID- 1494537 TI - A cis-acting element involved in mouse tyrosinase gene expression and partial purification of its binding protein. AB - The tyrosinase gene is specifically expressed in melanocytes. Understanding the molecular basis of tissue-specific expression of the tyrosinase gene will greatly explain the mechanisms controlling pigmentation. We report a nucleotide sequence, TGATGTATTC, located -236 base pairs upstream of the transcription start site, that enhances tyrosinase gene expression in mouse melanoma cells. The sequence is referred to as the tyrosinase element-1 (TE-1). TE-1 was protected from DNase I cleavage by pigment cell nuclear extracts but was not protected by non-pigment cell nuclear extract. Partial purification of TE-1 binding protein (TEBP-1) was performed from the B16 mouse melanoma cell nuclear extract using biotin-cellulose affinity chromatography. The affinity-purified fraction exhibited binding to the DNA fragment containing TE-1, and to a synthetic oligomer representing TE-1. UV cross-linking indicated that the size of TEBP-1 is approximately 49 kD. TE-1 also directed enhanced CAT activity in the B16 melanoma cells but not in non-pigment cells. These data indicate that TE-1 may be an enhancer element that is responsible for pigment cell specific expression of the tyrosinase gene. PMID- 1494538 TI - Isolation and characterization of a chicken tyrosinase cDNA. AB - Complementary DNA clones coding for chicken tyrosinase were isolated from retinal pigmented epithelium of chicken embryo. Sequence analysis shows that one of the cDNA clones consisting of 1,997 nucleotides has an open reading frame coding for 529 amino acids. The deduced protein has nine N-glycosylation sites and a transmembrane region. A sequence comparison of the deduced chicken tyrosinase with the mouse and human homologues revealed that amino acid sequences are conserved for the entire polypeptides. Seventy-two percent and 73% of amino acids in the chicken sequence are identical to that of the mouse and human tyrosinases, respectively. Histidines neighboring the postulated copper-binding sites and the cysteines are well conserved. RNA blotting analysis showed that a major transcript of 2.5 kb is detected in retinal pigmented epithelium of a 9-day-old chicken embryo. PMID- 1494539 TI - Cystic hygroma and congenital diaphragmatic hernia: early prenatal sonographic evaluation of Fryns' syndrome. AB - We report a case of cystic hygroma and diffuse lymphangiectasia detected by sonogram at 12 weeks' gestation. Fetal karyotype was normal. At 20 weeks' gestation, herniation of the bowel into the chest was noted. At delivery, the infant was diagnosed as having Fryns' syndrome. This is the first reported case of Fryns' syndrome presenting with cystic hygroma. PMID- 1494540 TI - Prenatal diagnosis of Chediak-Higashi syndrome. AB - We report the first prenatal diagnosis of an affected fetus with Chediak-Higashi syndrome (CHS). Diagnosis was accomplished via fetal blood sampling at 17 menstrual weeks and was confirmed after birth. Retrospective measurement of the largest acid phosphatase-positive lysosomes in cultured amniotic fluid cells and chorionic villus cells showed that in CHS these lysosomes are significantly larger than those in normal cells. This method may be used for prenatal diagnosis of CHS by amniocentesis and chorionic villus sampling (CVS). PMID- 1494541 TI - Screening for fetal Down syndrome with maternal serum hCG and oestriol: a prospective study. AB - We report the preliminary results of a prospective study aimed at evaluating the effectiveness of Down syndrome (DS) screening using second-trimester measurement of maternal serum human chorionic gonadotrophin (hCG) and unconjugated oestriol (uE3) together with maternal age. Reference values for hCG, uE3, and the hCG/uE3 ratio in normal pregnancies were established from more than 3000 normal gestations and found to follow a log-normal statistical distribution. Risk evaluation was made using reference values for affected pregnancies from retrospective studies. Screening of 10,000 women under 38 years resulted in 412 amniocenteses and the prenatal diagnosis of six cases of DS, whereas four cases remained undetected until term. In a parallel study, diagnostic amniocentesis was performed in women over 38 years and in women with a previous affected child, and an evaluation of the risk of fetal DS based on serum hCG and uE3 levels was made in all cases. Fourteen cases of DS were detected. Median values for hCG and uE3 in the 24 affected pregnancies were close to the 90th and tenth centiles of the normal reference values, respectively, and thus are in good agreement with the values reported by others in retrospective studies. PMID- 1494542 TI - Rare non-mosaic trisomies in chorionic villus tissue not confirmed at amniocentesis. AB - This paper reports eight cases of non-mosaic, rare, and typically lethal trisomies diagnosed in chorionic villi and not confirmed by amniocentesis. Four cases were 47,XX,+16; two cases were 47,XX,+2; one was 47,XX,+12; and one was 47,XY,+7. There have been no known complications in any of these gestations. These eight cases were found in a series of approximately 12,000 samples processed in our laboratory (0.07 per cent). We conclude that (1) rare non-mosaic trisomy not reflecting the fetal condition is an occasional source of diagnostic ambiguity in chorionic villus sampling; and (2) when encountered, a follow-up amniocentesis should be recommended to the patient to confirm or rule out the abnormality. We propose the term 'confined placental abnormality' to describe non mosaic trisomies and other related abnormalities found only in chorionic tissue. PMID- 1494543 TI - A simple electrophoretic procedure for fetal diagnosis of beta-thalassaemia due to short deletions. AB - This study describes three couples at risk for homozygous beta-thalassaemia in which one of the partners carried a short deletion beta-thalassaemia defect. Detection of short deletions in trophoblast DNA was accomplished by the very simple procedure of non-denaturing polyacrylamide gel electrophoresis. This method may be applied to detect beta-thalassaemia mutations due to deletion or addition of more than two nucleotides. PMID- 1494544 TI - Prenatal identification of a 45,X/46,Xder(Y) mosaicism and confirmation by high resolution cytogenetics and fluorescence in situ hybridization. AB - A 45,X/46,Xder(Y) mosaicism detected prenatally was shown to have a rare Y inversion-duplication or Y/Y translocation which can only be identified by a combination of high resolution cytogenetics and fluorescence in situ hybridization. The present data indicate the usefulness and importance of chromosome-specific probes in the identification and characterization of chromosome rearrangements. PMID- 1494545 TI - Prenatal diagnosis of giant cystic hygroma: prognosis, counselling, and management; case presentation and review of the recent literature. AB - Cystic hygromas have historically been associated with a grim prognosis when discovered during prenatal sonographic study of the fetus. This same grim prognosis is not observed by the paediatric surgeon who evaluates the neonate or paediatric patient. We present a fetal patient with a massive anterior cystic hygroma discovered in the third trimester prior to 30 weeks. This case and a review of the literature suggest tailoring the prognosis by category when counselling patients: (1) first trimester, normal karyotype--good; (2) first trimester, abnormal karyotype--poor; (3) second trimester and early third--poor to guarded; and (4) mid to late third trimester--good. PMID- 1494546 TI - Analysis of chromosome 21 copy number in uncultured amniocytes by fluorescence in situ hybridization using a cosmid contig. AB - A comparison of the use of chromosome 21-specific libraries, DOP-PCR 21 paints, yeast artificial chromosome (YAC) clones, single cosmids, and a 21q cosmid contig as probes for the detection of the copy number of chromosome 21 in interphase cells by fluorescence in situ hybridization shows that the cosmid contig is a satisfactory probe for interphase analysis of chromosome 21. The contig cCMP21.a, which is 55 kb in length, is highly chromosome 21-specific and produces intense, compact signals in a high proportion of interphase cells. A retrospective blind analysis of coded uncultured amniotic fluid samples correctly detected four trisomy 21 cases out of 49 samples. PMID- 1494547 TI - Prenatal diagnosis of monosomy 18 and ring chromosome 18 mosaicism. AB - The case of monosomy 18/ring chromosome 18 mosaicism which was detected prenatally by amniocentesis is presented. The pregnancy was terminated in week 18. Autopsy showed complex malformation of the fetus consisting of cebocephaly, hypotelorism, microphthalmia, severe defects of brain development, and arrest of placental maturation. PMID- 1494548 TI - Normal karyotype in cultured chorionic villus cells, but mosaicism in amniotic and fetal cells. AB - A case with a normal male karyotype in cultured chorionic villus cells, but 46,XY/45,X/46,X,i(Yq) mosaicism in amniotic and fetal tissue is reported. The fetus was a phenotypic male. Pathological examination revealed discrete features, which might indicate a syndrome, and histological examination showed large, bright cells in the tubules of the testes. Possible explanations for discordance between the karyotype of embryonic and extraembryonic tissue are discussed. PMID- 1494549 TI - Neonatal alloimmune thrombocytopenia due to anti-P1A1 (anti-HPA-1a): importance of paternal and fetal platelet typing for assessment of fetal risk. AB - Neonatal alloimmune thrombocytopenia (NAIT), which usually involves sensitization to P1A1 (HPA-1a), may have devastating complications for the fetus. These may be prevented by antenatal treatment of severe cases with either maternally administered high-dose gamma-globulin and/or repeated intrauterine platelet transfusions. Determination of the paternal platelet phenotype is useful for counseling parents who have had one or more affected pregnancies. This report of an unaffected pregnancy in a woman with a history of previous pregnancies complicated by NAIT illustrates the role of paternal and fetal platelet phenotyping in managing existing pregnancies at risk of NAIT. PMID- 1494550 TI - Chromosomal abnormalities associated with a single umbilical artery. AB - A single umbilical artery was seen in 10 out of 117 cytogenetically abnormal pregnancies. The abnormal karyotypes found to be associated with a single umbilical artery were trisomy 18 (n = 5), monosomy X (n = 2), triploidy (n = 1), sex chromosome (47,XYY; n = 1) and translocation (46t(X,5)(q13p15);n = 1). With the exception of the translocation case, all cases with a single umbilical artery had anatomical defects which were detectable ultrasonographically. This suggests that a single umbilical artery alone is not an indication for prenatal fetal karyotyping. PMID- 1494551 TI - First-trimester prenatal exclusion of PIBIDS syndrome with normal DNA excision repair on chorionic villus cells. PMID- 1494552 TI - Use of fluorescence in situ hybridization to detect trisomy 18 in the direct preparation of a chorionic villus biopsy. PMID- 1494553 TI - Prenatal diagnosis of second-trimester congenital varicella syndrome. PMID- 1494554 TI - Prenatal diagnosis of Roberts syndrome. PMID- 1494555 TI - [Psoriasis: therapeutic perspectives]. PMID- 1494556 TI - [Diagnosis of lymphatic metastases in pelvic urologic tumors. Value of puncture biopsy]. AB - In 119 patients with pelvic urogenital tumours the diagnosis of lymph node metastasis was made by lymphography-guided fine needle biopsy. The results of this technique, performed without anaesthesia and devoid of morbidity, could be interpreted in 88 percent of the cases. In the search for micro- and macroscopically invaded lymph nodes fine needle biopsy had a sensitivity of 66 percent, a specificity of 100 percent, a positive predictive value of 100 percent and a negative predictive value of 92.3 percent. In cases with macroscopically invaded nodes its sensitivity was 82.3 percent. PMID- 1494557 TI - [Isolation of Toxoplasma gondii by cellular culture in HIV infected patients]. AB - Nine hundred and eight biological samples obtained from HIV-infected patients were examined for Toxoplasma gondii by a tissue culture method. Sixty-two isolations of Toxoplasma gondii were made in 43 patients. Fourteen isolations were made from tissue biopsies (brain 4, striated muscle 2, liver 1), bone marrow aspirates (4 cases), pericardial or pleural effusions (3 cases) and vitreous body (1). In 6 cases, a parasitic dissemination was evidenced by the demonstration of Toxoplasma in blood or other tissues or body fluids. Toxoplasma organisms were demonstrated in the bronchoalveolar lavage fluid of 19 patients; this was associated with a parasitaemia in 6 of the 10 patients whose blood sample was cultured at the same time. Among 273 blood samples cultured, 29 were positive for Toxoplasma (24 patients); all patients with parasitaemia had clinical symptoms, but only 8 of them had clinical or radiological symptoms suggestive of a cerebral localization; this suggests that the presence of a parasitaemia is fairly indicative of an extra cerebral localization of toxoplasmosis. In 11 patients, blood was examined after treatment was initiated; in 8 patients parasitaemia was undetectable at the first examination after treatment (1 to 15 days after initiation of therapy), whereas in 3 patients sampled 1, 4 or 6 days respectively after treatment a persistent parasitaemia could be demonstrated. These results clearly show that the tissue culture method is efficient and sensitive to provide an early evidence of infection (4 days), and may prove useful to evaluate therapeutic effectiveness. PMID- 1494558 TI - [Appendectomy, a risk factor for ectopic pregnancy]. AB - As part of a case-control study of ectopic pregnancy, we evaluated the potential etiological role of appendectomy. Previous appendectomy was associated with an increased risk of ectopic pregnancy (adjusted Odds-ratio: 2.2; 95 percent CI: 1.5 3.2). Ruptured appendix did not appear to be more strongly associated with an increased risk of ectopic pregnancy than unruptured appendix. Such confounding factors as absence of pathological diagnosis of appendicitis and relationship between age of appendectomy and age of first sexual intercourse are discussed. This study provides an additional argument in favor of laparoscopy in childbearing age to diagnose appendicitis and salpingitis. PMID- 1494559 TI - [Hermaphroditism and male pseudohermaphroditism]. AB - In the human embryo, sex is all in the genes. Later on, the male and female sexual characters, which are products of the expression of all individual genomes, differentiate men from women. In this paper, the embryogenesis and morphology of true hermaphroditism and male pseudo-hermaphroditism are studied. These are intersexual states determined by errors in genital programme transmission. A relationship is established between the biochemical identification of substances secreted by the testis and the evolution of sexual characters. The genesis of sexual abnormalities according to the stage when the testicular deficit appears is envisaged. The clinical, anatomical, histological and biochemical aspects of these intersexual states are described. PMID- 1494560 TI - [Primary hepatic actinomycosis, a tumor of diagnostic difficulties]. PMID- 1494561 TI - [Celiosurgery and CO2 laser: value of a system with infraguide transmission]. PMID- 1494562 TI - [Transmission of HIV infection in Madagascar. Risk factors of contamination]. PMID- 1494563 TI - [Avoidable perinatal mortality. Attempted evaluation and significance]. PMID- 1494564 TI - [Epididymal dirofilariasis mimicking testicular torsion in an adolescent]. PMID- 1494565 TI - [Somatostatin analogues in the treatment of paraneoplastic hypercorticism]. PMID- 1494566 TI - [Acute hemolysis after early pneumococcal revaccination in a patient splenectomized for autoimmune hemolytic anemia]. PMID- 1494567 TI - [Vitiligo-thrombocytopenic purpura association: a developing multiple autoimmune syndrome]. PMID- 1494568 TI - [Enzymatic reactions in biotechnology (48th Bach lecture)]. AB - The paper is the 48th Bach Lecture presented under the same title. It covers the biochemical mechanisms of the biogenesis of microbial biosynthetic products, role of acetyl-CoA, function of the succinate-glycine cycle, reactions of the hexose monophosphate pathway of carbon metabolism. The reversible action of hydrolases in enzymatic catalysis and degradation of xenobiotics are discussed. The data on redox reactions are pooled. Such modern biotechnological processes as epoxidation, synthesis of acrylamide and some monomers involved in chemical syntheses of polymers, synthesis of oligosaccharide and fluorine-containing amino acids are considered. Promising commercial applications of biocatalysis are discussed. PMID- 1494570 TI - [Various aspects of regulating the synthesis of ergot alkaloids]. AB - The regulation of ergot alkaloid (EA) biosynthesis both at the genetic level and at the level of physiological realization is discussed. The genes involved in EA synthesis are shown to be under rigorous metabolic control. Circumstantial evidence links the initiation of the EA metabolism to changes in some parameters viz morphological feature, concentrations of enzymes and their substrates, contents of nutrients, and external stress. PMID- 1494569 TI - [Methods of detecting and determining nitrogen-containing mycotoxins]. AB - The influence of various nitrogen functional groups used for extraction cleanup and determination of N-containing mycotoxins (NM) in feeds and foodstuffs have been considered. TLC and LC are the most common techniques for detection and determination of nitrogen-containing mycotoxins. Gas chromatography has been used for determination (with or without derivatization) of several nitrogen-containing mycotoxins and/or their degradation products. Immunochemical techniques, in particular ELISA are available for only a very limited number of NM (e.g. ochratoxin A). Numerous methods for determination of ochratoxin A in feeds, grains, animal products and other foodstuffs have been developed. Methods for which recoveries have been carried out on spiked samples are also available for several other NM. PMID- 1494571 TI - [Biosynthesis of ergot alkaloids. Some new results on an old problem (Review)]. AB - The biosynthetic pathway leading from L-tryptophan, mevalonic acid and methionine to the tetracyclic ergoline ring system of the ergot alkaloids in Claviceps species is reviewed. This pathway entails many mechanistically intriguing features. Recent studies are also discussed which reveal the stereochemical course of the isoprenylation of tryptophan and of the N-methylation of dimethylallyltryptophan (DMAT) and which shed some light on the likely steps leading from the open-chain precursors, N-methyl-DMAT to the tricyclic intermediate, chanoclavine-1. Finally, some plans are outlined to probe the evolutionary relationship of ergot alkaloid biosynthesis in fungi to that in higher plants of the family Convolvulaceae. PMID- 1494572 TI - [Nitrogen-containing mycotoxins: tremor-causing mycotoxins]. PMID- 1494573 TI - [Penicillium-species fungi--producers of ochratoxin A in grain]. AB - The occurrence of ochratoxin A and ochratoxigenic fungi in the commercial batches of various domestic grains (wheat, rye, barley, corn and rice) has been studied. Penicillium cyclopium, P. viridicatum and P. chrysogenum isolated from grain synthesized on a sucrose-yeast medium predominantly patulin, penicillic and kojic acids. Only 4.4% of the fungal isolates were able to synthesize ochratoxin A. The concentration of the mycotoxin accumulated by the fungi was less than 500 micrograms/kg. 230 samples of wheat and 502 samples of corn were examined. The analysis showed that ochratoxin A was present in 0.9% and 0.1% of samples tested, respectively. The mycotoxin accumulated in grain mainly during its spontaneous heating and was concentrated in mold-damaged kernels. PMID- 1494574 TI - [Fumonisins--new metabolites of Fusarium moniliforme--as contaminants of corn]. AB - Strains of the Fusarium moniliforme fungi, widely distributed contaminants of maize are shown to be highly toxic and carcinogenic and cause various animal and human diseases. The effect of temperature and incubation period on the production of fumonisins by F. moniliforme have been studied. The overall maximum yield of fumonisins was 17.5 g/kg maize. A high-performance liquid chromatographic method for the quantitative determination of fumonisins is proposed. The structural analysis of their tetramethylethers was performed by the mass-spectrometry method. It has been established that fumonisins are causative factors in the toxicity of horse leukoencephalomalacia. The possible role of fumonisins in the etiology of oesophageal cancer is discussed. PMID- 1494576 TI - [A bioluminescence method of determining the activity of NAD-dependent hydrogenase]. AB - An analytical multienzyme system composed of NAD-dependent hydrogenase of Alcaligenes eutrophus, and reductase and luciferase from luminous bacteria was studied. The rate of luminescence increase of this system was found to be proportional to hydrogenase activity. The apparent Michaelis constants for NAD and hydrogen were determined (5 and 40 microM, respectively). The pH optimum is 7.5-9.0. Over the NAD concentration range from 20 to 100 microM, the rate of luminescence increase changed by less than 10%. At higher concentrations of NAD a monotonous decreasing of the rate of luminescence increase was observed. The proposed multienzyme system can be used for measuring the hydrogenase activity and hydrogen concentration. The high sensitivity to hydrogen (0.1 nmol in sample) and to hydrogenase (0.5 mU) and specificity of the system enable its application in the development of a biosensor for rapid detection of hydrogen in a medium. PMID- 1494575 TI - [Hepatotoxicity of cyclochlorotine--a cyclic peptide produced by Penicillium islandicum]. AB - Toxicological investigations of "Yellow Rice" which have been contaminated with various Penicillium species have shown that Penicillium islandicum apart from well-known hepatotoxic mycotoxin, lyteoskyrin synthesizes cyclochlorotine (chloropeptide, CP), which is also hepatotoxic. Isolation of chloropeptide and its chemical characteristics, acute toxicity and biochemical alterations, tissue distribution and excretion, deformation of hepatic cells, and interaction with cytoskeleton filaments are described. It is shown that the hepatotoxicity of CP is inactivated by dehalogenation of CP by the cytochrome P-450 system. PMID- 1494577 TI - [New developments and knowledge in research of respiratory sounds]. PMID- 1494578 TI - [Pleural diseases in magnetic resonance tomography (MRT)]. AB - MR images of 48 patients with histologically confirmed benign and malignant diseases of the pleura were retrospectively compared with CT and bioptically/surgically obtained findings. In 47/48 patients pathological changes of the pleura were visualized by increased signal intensities on T2-weighted and contrast enhanced T1-weighted MR images. This lead to a slightly improved sensitivity compared to CT, where pathological pleura findings were confirmed in 45/48 patients. MRI was able to identify 24/28 confirmed pleural effusions, whereas CT was successful in 26/28 patients. In two cases effusions not identified on CT were visible on T2-weighted MRI. 4 pleural effusions were missed with MRI.. On CT images differentiation of pleural changes vs effusions or adjacent lesions of lung parenchyma was successful in 20/28 and in 17/23 cases, respectively. Contrast enhanced T1-weighted images achieved the highest diagnostic accuracy with 22/28 and 20/23 cases, respectively. Signal intensities on MRI were unsuitable as sole criterion for the differentiation of benign and malignant diseases of the pleura. Contour and pattern of spreading of pleural changes were helpful in differential diagnosis. Nodular changes, thickening of more than 10 mm and mediastinal, circumferential and entire hemithoracic affection of the pleura were suggestive for malignant pleural disease. Infiltration of the diaphragm and the chest wall were most indicative for malignancy; here MRI (2/2 resp. 18/19 cases) was superior to CT (0/2 resp. 14/19 cases). CT was superior in the detection of pleural calcifications and osseous destruction.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1494579 TI - [Expression of TNF-alpha in alveolar macrophages after stimulation with quartz dust, welding fume dust and asbestos fibers]. AB - Alveolar macrophages have a potential for expressing and excreting many factors that are immunologically active and active on cytokines (monokines and lymphokines) and are thus indirectly involved in the genesis of pulmonary fibroses. One of these factors is the tumour necrosis factor alpha (TNF alpha). In the study presented here, the expression of TNF alpha-mRNA was investigated in macrophages stimulated in vitro with quartz dust, dust from cinders of welding furnaces, and asbestos, using non-radioactive in situ hybridization. There was a marked dependence of the expression of this cytokine on both time and stimulation. Macrophages stimulated by quartz dust showed the highest rate of expression compared with controls and other related stimuli. In addition, all stimuli yielded an expression that was elevated for a short period only and reached its peak after four hours. The results permit the conclusion that various professionally inhaled dusts possess different risk potentials in respect of lung damage mediated by macrophages and do not behave uniformly. PMID- 1494580 TI - [The value of physical therapy with VRP 1-Desitin ("Flutter")]. AB - Preliminary examinations with an innovative device for physiotherapy, VRP 1 Desitin ("Flutter"), in patients suffering from chronic mucus retention and bronchial collapse gave encouraging results. Therefore, we tried to confirm these findings and to evaluate the use of this new physiotherapy. It is based on oscillations of air in the respiratory tract during expiration (rate about 2 to 32 Hertz) diminishing adhesiveness of bronchial mucus and bronchial collapse. Pressure and flow changing depend on the position of mouth-piece and effort of breathing. In order to establish the efficiency of the VRP 1 a comparing investigation was initiated. 20 patients with cystic fibrosis, aged 7 to 28 years, performed physiotherapy with VRP 1 and autogenic drainage (AD), respectively, in a randomized order one after another, each physiotherapy taking twenty minutes. The expectorated sputum was weighed by means of a precision balance. Mean values during VRP 1 treatment were 5.0 g (range 0 to 12.0 g), during AD 4.8 g (range 0 to 11.7 g). There was no statistical difference (p < 0.05). The results were not influenced by the order of physiotherapy. CONCLUSIONS: VRP 1 physiotherapy is as effective as AD with respect to sputum elimination. In opposite to other methods not requiring a helping person it is simple to teach and to learn. It may be performed by young children (> or = 3 years) and adults, also in combination with inhalation. Thus, VRP 1 appears to be a real enrichment in physiotherapy. PMID- 1494581 TI - [Spontaneous lung torsion after acute pleuropneumonia]. AB - We report on a case of spontaneous torsion of the right lung in a 59 years old woman which occurred after an acute pneumonia followed by chronic empyema and progressive dyspnea with marked respiratory disability. Despite extensive diagnostic procedures including bronchoscopy and bronchography the true diagnosis could be established only by thoracotomy performed in order to cure the chronic empyema. The abnormal hilar rigidity by preexisting calcified sarcoidosis of the lymph-nodes is suggested to be a major risk factor for developing lung torsion as it has been emphasized in a few similar reports from the literature. Surgical reposition of the displaced lung is the most effective treatment and can save and restitute lung structure and function even in patients with prolonged course and delayed diagnosis. PMID- 1494582 TI - [Primary pulmonary nodular amyloidosis and multiple emphysematous bullae in Sjogren syndrome]. AB - The authors report on a very rare case of an isolated primary nodular pulmonary amyloidosis with multiple emphysematous bullae in Sjogren's syndrome. The circular foci present in both lungs in disseminated form were immunohistochemically speaking amyloid deposits of the AL-lambda type. There were no pointers to other organ manifestations or monoclonal immunoglobulins in the serum and/or urine. PMID- 1494583 TI - [Evaluation of a request for information in a sample of health workers at the Mantova U.S.S.L.47]. PMID- 1494584 TI - [Evaluation of the quality of nursing assistance: an experiment in Galles del Sud]. PMID- 1494585 TI - [Project for the evaluation of the quality of nursing assistance]. PMID- 1494586 TI - [An Italian nurse obtains a nursing doctorate in Sweden. A PhD thesis in Public Health at the Nordic School of Public Health in Goteborg, Sweden, 1992]. PMID- 1494587 TI - [Law of government authority for the explanation and revision of disciplines in the field of health, public employment, social security and domestic finances]. PMID- 1494588 TI - [Another sketch for reform legislation in the health, nursing and technical professions and rehabilitation]. PMID- 1494589 TI - [A project of permanent information through the introduction of a nursing portfolio on a specific subject]. PMID- 1494590 TI - Antidepressants--do they decrease or increase suicidality? AB - Based on an intensive review of the literature, the question was analyzed as to whether antidepressants have an influence on suicidality and whether there are specific differences between certain subgroups of antidepressants. In general, antidepressants reduce suicidal ideations in depressive patients. A faster onset of this kind of action in serotonin-reuptake inhibitors is not yet completely proved. The hypothesis, described by clinicians, of a specific suicidality increasing risk being associated with a certain group of antidepressants (e.g., antidepressants with a drive-enhancing, non-sedating clinical profile, drugs with a certain biochemical mode of action) has hitherto not been confirmed in control group studies. An unspecific induction of suicidality, observable also under other psychoactive drugs, appears to be quite rare and occurs only under predisposing conditions, such as personality disorders and comedication with other drugs. PMID- 1494592 TI - The dexamethasone suppression test as an indicator of suicide: a meta-analysis. PMID- 1494591 TI - Brofaromine in panic disorder: a pilot study with a new reversible inhibitor of monoamine oxidase-A. AB - The therapeutic efficacy of brofaromine--a new reversible and short acting MAO-A inhibitor--was evaluated in 14 inpatients with a panic disorder. In an open trial, the patients were treated with placebo during the first week and with 150 mg brofaromine per day during the following four weeks. In all patients a distinct improvement in both anxiety and depressive symptoms was observed under the active drug. Treatment outcome was the same in patients with and without a concomitant major depressive episode. No side-effects of any note were reported. Our findings suggest that the MAO-A inhibitor brofaromine is an effective drug in the treatment of anxiety disorders. PMID- 1494593 TI - Therapeutic drug monitoring of psychotropics: report of a consensus conference. PMID- 1494594 TI - Haloperidol and lorazepam combined: clinical effects and drug plasma levels in the treatment of acute schizophrenic psychosis. AB - In 61 acute schizophrenic patients the effects of haloperidol (HPL) and lorazepam combined vs. HPL alone and the interaction between these drugs were evaluated. Patients were assigned to groups randomly. The study design was open. Study duration was 28 days. Psychopathology was evaluated on the basis of BPRS scores. Extrapyramidal side-effects were rated according to Simpson and Angus (1970). Pharmacological parameters included serum levels of lorazepam, HPL, and reduced HPL. Mean daily lorazepam dosage was 0.05 mg/kg, mean HPL dosage 0.5 mg/kg. None of the patients treated with lorazepam and HPL achieved better BPRS total or subscores, nor did their condition improve faster than in patients treated with HPL alone. A significant linear relationship between lorazepam serum levels and oral dosage was found, but none between lorazepam serum levels and BPRS total score, subscore reduction, or extrapyramidal side-effects. The authors conclude that beneficial effects of lorazepam in the treatment of acute psychosis are scant and may not justify the risks incurred with routine comedication of lorazepam. PMID- 1494595 TI - Electroconvulsive therapy in a geriatric patient with multiple bone fractures and generalized plasmocytoma. AB - Electroconvulsive therapy (ECT) is a highly effective treatment for patients with severe major depressive disorder. ECT can safely be administered even to medically ill, high-risk patients; we report on the complete remission of depressive psychopathology following five unilateral ECT treatments in a suicidal geriatric patient with concurrent prior venous thrombosis, coronary heart disease, multiple myeloma, glaucoma, bilateral petrous bone fractures, and a femoral neck fracture. Most medical complications during ECT can be managed with interdisciplinary cooperation. PMID- 1494596 TI - Antidepressant-associated mania. PMID- 1494597 TI - [Character formation and interactions]. AB - This paper details the impact of constitution endowment, e.g. temperament and interaction with the parents, e.g. transaction on character development. Adult and child analytic material are used to illustrate this process. PMID- 1494598 TI - [A psychoanalytic model at the "Menninger Clinic"]. AB - This paper describes the psychiatric treatment of adolescents on one of the long term inpatient units of the Children's Hospital at Menninger in Topeka, Kansas. The conceptual framework for this treatment is psychoanalytic. Dr. Stamm's paper describes how hospital's "holding environment" (Winnicott, 1965) and the individual and family therapy converge to facilitate emotional growth and change. Central to psychoanalytic hospital treatment is an understanding of transference/countertransference with each adolescent. PMID- 1494599 TI - [Tourette's syndrome: psychopathology of development in a model of neuropsychiatric dysfunction in children]. AB - The complex neuropsychiatric disorder described by Gilles de la Tourette is a childhood onset, generally lifelong condition diagnosed on the basis of multiple, everchanging motor and vocal tics. Genetic evidence indicates that the vulnerability to Tourette's Syndrome (TS) is transmitted as an autosomal dominant genetic trait. This vulnerability has a broad range of expression, from full blown TS to chronic multiple tics; an alternate manifestation may be obsessive compulsive disorder. There is also a broad range of severity, from quite mild to incapacitating. No specific neuroanatomical or neurochemical basis has yet been discovered, but the basal ganglia and dopaminergic systems have been implicated. Children and adults with TS experience the intrusion into consciousness of unwanted and disturbing sensations, thoughts and desires; they repeatedly experience the need, arising from an "alien" force within themselves, to produce sounds and actions which they try to resist but to which they eventually capitulate. Their symptoms elicit strong responses from family and others, as well as themselves. Psychoanalytically guided, clinical study can help illuminate the inner world of individuals with TS and define the pathways between biological vulnerability and clinical expression. Treatment often requires a combination of approaches, including guidance, psychotherapy and, in a minority of cases, the careful use of medication. Over the past decade, TS has served as a model developmental disorder for studying the interactions between biological vulnerability and environmental responses in the emergence of a clinical disorder and in the shaping of a child's character. During the next years, further advances in the study of TS should help clarify basic issues in the transmission of constitutional vulnerability and suggest approaches to prevention and early intervention. PMID- 1494600 TI - [Reflections of a child psychiatrist on the diagnosis and hospitalization in psychiatry of adults: an experience of David Rosenhan]. AB - In the 1970s, David Rosenhan and seven other persons were hospitalized in twelve different psychiatric hospitals, pretending having heard voices uttering such words as void, hollow, thud. They were immediately hospitalized with a diagnosis of schizophrenia and, for one of them, of bipolar condition. Right after entering hospital, they reversed to normal behavior. None of them had a psychiatric history. Nevertheless, they were released after a time lapse of 7 to 52 days with a mean of 19 days. Release diagnosis was the same as the admission with the adjunct "in remission". D. Rosenhan points out the contextual and incertain aspect of the diagnosis and underlines the fact that it is apparently impossible to consider as being normal a person who has been admitted to a psychiatric hospital. Psychiatric labels stick to the skin. D. Rosenhan describes the pervasive boredom in a psychiatric hospital and the general set which leads to de personalization. C. Chiland gives some precisions on what lead D. Rosenhan to undertake such an "experiment". She analyzes the reactions of the American psychiatric community which felt attacked in it's knowledge to the point of entirely rejecting the message. Indeed the criticism concerned the contextual aspect of diagnosis in the framework of the Gestaltpsychology and called to a necessary awareness of what is experienced by a hospitalized patient. Instead of seeking solutions to ward off the negative effects of the psychiatric hospital, effects that are inherent to any total institution, the community has rejected Rosenhan's experiment as being based on faking. Should a child psychiatrist feel securely innocent? The danger of labelling does exist for the children and their parents. Although a one-way choice in the dynamic contradiction between segregation and integration is not possible, one nevertheless has to remain vigilant regarding the institutions, even in day-care ones, so as to avoid imprisoning the child in rejection or stagnation attitudes. PMID- 1494601 TI - [Training in motor skills and psychopathology. Climbing with psychotic children]. AB - The author investigates learning skills in psychotic and borderline children through the physical activity of climbing. Motor skills are considered as an interaction between the subject and his/her environment. Motor learning skills have been studied throughout 6 training sessions in rock-climbing. Etho-clinical methods of investigation allow to assess behaviors and the meaning given by the subject to different forms of action. The author emphasizes here the pleasure/anxiety dimensions of this activity. Results show remarkable learning skills in these children. Significant increase in motor activity and in the height reached point to an obvious integrity of the mechanisms necessary to motor acquisitions. These results are closely linked with the characteristics of rock climbing, a sport involving clinging behaviors and leading to a mastering of the primary anxiety of loosing support. PMID- 1494602 TI - [Disease models and models of handicap in psychiatry]. AB - Throughout psychiatric history, the handicap model has been referred to a mineral image as opposed to the vegetal image of disease. The structural model, after Freud, seeks to overcome the opposition between disease and handicap. Present day disregard for this model, especially in the United States, stems from economical and ideological reasons. The come-back of a psychopathology of "faculties" linked to the notion of deficiency and reinforced by fascination with computers, also represents the need of humankind to believe in an incorruptible soul. PMID- 1494603 TI - [Psychosis, mental handicap, motor handicap]. AB - Child mental disorders have to be considered both in terms of morbid process and handicap, the two aspects entertaining a dialectical relationship. The authors support this opinion through a nationwide epidemiological study of mental deficiency and by a long term follow-up case. PMID- 1494604 TI - Collagenase activity in oral submucous fibrosis. AB - Oral submucous fibrosis (OSF) is characterized by an abnormal accumulation of collagen fiber in oral submucosa. OSF is a collagen disease and is also regarded as a precancerous lesion. In the previous study, we discovered that the collagen content in oral mucosa of OSF is statistically higher than in normal mucosa. This research examined the relationship between the fibrosis and collagenase activity. Collagenase activity was determined by using soluble 14C-glycine-labeled collagen (9813 cpm/200 micrograms/tube) as a substrate in a solution incubated for 30 hours at 35 degrees C. The results showed that the collagenase activity of the OSF was much lower than that of normal oral mucosa (65.23 +/- 19.49 units/g tissue in normal mucosa vs. 29.48 +/- 5.69 units/g tissue in OSF). Furthermore, the cleavage pattern revealed by SDS-Polyacrylamid gel electrophoresis (SDS-PAGE) confirmed that the partially purified OSF collagenase was likely to be typical mammalian collagenase, with a molecular weight of about 68.0 kDa. PMID- 1494605 TI - Menadione-induced cardiotoxicity is associated with alteration in intracellular Ca2+ homeostasis. AB - Cardiotoxicity of menadione was elucidated in neonatal rat cardiomyocytes. When incubated with menadione, contraction of myocytes initially slowed down and eventually stopped. Later blebs appeared on the cell surface, leading to cell degeneration. During the time of diminished cellular contraction, a large portion of endogenous ATP was depleted whilst intracellular Ca2+ levels were increased. However, if menadione was washed out prior to termination of contraction, the myocytes survived and most of the cells resumed regular contraction. Preincubation of the cells with diltiazem (a Ca2+ antagonist), or fura-2 acetoxymethyl ester (a chelate for Ca2+), or antipain (a proteinase inhibitor) suppressed menadione's ability for cellular damage. These results indicate that menadione is toxic to cardiomyocytes, and that the increase of intracellular Ca2+ is related to the mechanism of cardiotoxicity of menadione. PMID- 1494606 TI - Biochemical comparisons of matrix proteins extracted from healthy human alveolar bone, dentin and cementum. AB - Matrix proteins of bone, dentin and cementum have been shown to play a role in bone induction during the mineralization process, and in regulating the activities of several types of mesenchymal cells. Whether these biological functions are mediated through the same mechanism or whether there is specific modulation in each biological process is still open to speculation. The purpose of this pilot investigation was to compare the non-collagenous proteins among these tissues. Bone and teeth, obtained from clinically healthy subjects, were sectioned into 1 mm thick pieces. With the aid of a dissecting microscope, cementum and dentin were separated and collected. Tissue specimens were extracted sequentially in three steps by solutions containing 0.5 M acetic acid, 4 M Guanidine/0.5 M EDTA, and 250 units/ml bacterial collagenase, respectively. Proteins extracted were dialyzed, lyophilized and then further analyzed by both 10% SDS-PAGE (1-D) and two-dimensional (2-D) SDS-PAGE. Comparison showed that the three extraction buffers had relatively different extraction capacities within and among each tissue. The components extracted by acetic acid and Guanidine/EDTA were similar, but seemed different from that extracted by bacterial collagenase as shown by 10% SDS-PAGE. Two-dimensional SDS-PAGE further characterized numerous distinct protein spots from bone (MW of 61, 55, 40, 35, 34, 33 kD and eleven distinct spots which showed MW between 10 and 29 kD, pI range of 5.6-6.4), dentin (MW of 59, 54, 35, 28, 25, 24, 21 kD), and cementum (MW of 71, 64-65, 58, 55, 52, 50, 47, 43, 40, 31, 19 kD).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1494607 TI - Effects of working side interference on nocturnal bruxers. AB - The present study aimed to test the effects of experimentally placed working side interference on nocturnal bruxers with regard to the health and chewing motor behaviors of the masticatory system. Thirteen asymptomatic nocturnal bruxers, nine males and four females, aged 18-31 years old, were selected according to the including criteria. A metal overlay was fabricated and bonded on the tips and lingual inclines of buccal cusps of the upper second premolar and first molar of the habitual chewing side. It discluded the eccentric contacts without disturbing the centric occlusion. A light emitting diode system was used to record the chewing motor behaviors before (W0), immediately after (W1), one day after (W2), one week after (W3), and one month after (W4) placement of the working side interference. The healthy states of masticatory muscles and TMJs were examined at each session. The results showed: 1. High overlay debonding rate (60%). Among five subjects who were observed over 25 days, 80% showed grinding facets, and 40% showed grade I mobility on the overlay opposing teeth. None of the subjects complained of muscle or joint pain in the one month follow-up period. 2. The chewing movements shifted toward the non-interfered side with narrowed and vertical chews after placement of overlays. Two major responded chewing patterns were found according to the results of statistical analysis. 3. Sixty-nine per cent of the subjects showed higher mean closing velocity than the mean opening velocity at the W0 session.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1494608 TI - F. Hegelmaier: on memory for the length of a line. AB - A very early student project undertaken by Friedrich Hegelmaier (1833-1906), published in German in 1852, is republished in English translation. Slight though the experimental work is, it nevertheless occupies a unique place in the history of experimental psychology. It is the source whence Fechner had the method of constant stimuli, a method that continued in use as the preferred psychophysical method, substantially in the form described here, for more than a century. The experiment is arguably the first experiment in the modern sense of a systematic preplanned body of observations and has the glaring faults that one would expect in a very first experiment. Finally, Hegelmaier suggests the use of two simultaneous tasks as a means to investigate human performance, a full hundred years before that idea was realized in practice. If only he had continued in experimental psychology! PMID- 1494609 TI - Motion aftereffects with rotating ellipses. AB - The perceptual outcome and the motion-aftereffect duration generated by the rotation on the frontal plane of an ellipse with a bar depend on whether the bar is placed along the major or the minor axis. When the bar is placed along the minor axis, a stereokinetic transformation occurs, and the pattern looks like a tilting ring with a perpendicular bar moving rigidly with it. Placing the bar along the major axis prevents the stereokinetic transformation: subjects report deformations and relative motion of the bar with respect to the ellipse. We found that motion aftereffects last longer when the bar is placed along the minor rather than along the major axis. A series of experiments was carried out to investigate whether differences in aftereffect duration are related to the stereokinetic transformation. Results seem to suggest that they are not. PMID- 1494610 TI - Apparent distance reduction with moving stimuli (Tandem Effect): evidence for an attention-shifting model. AB - When two vertical rods move through a horizontal window in close succession, the Tandem Effect can be observed. It consists of a spatial illusion (distance between the rods looking smaller than it actually is) and a temporal illusion (under certain conditions both rods are seen simultaneously in the window, though the first rod has left the window before the second rod enters it). We report six experiments that explored the distance-reduction illusion and tested an attentional model of the effect. It assumes that attention is initially focused on the first rod and then shifted to the second, when it enters the window. The percept of the pair of rods is integrated from the first rod's position at the beginning, and the second rod's position at the end, of the focus shift. Consequently their subjective distance will be smaller than their physical distance by the distance that they travel during the focus shift. Experiments 1 and 2 established the Tandem Effect as an empirical phenomenon and showed that its size depends on stimulus parameters such as window size and movement speed. Experiments 3-5 tested specific predictions from the attentional model. Experiment 6 examined a further illusion, the Frohlich Effect, and showed that it can be subsumed under the model. The experiments produced some unexpected effects and some predictions from the model were only partly confirmed. It is shown that the main findings can be combined into two quantitative functions that describe the course of focusing. One implication is that visual attention does not "move" from one object to another; rather all attention shifts originate in the fovea. We discuss several alternative interpretations of our data and show that they are less satisfactory than the attentional model. PMID- 1494611 TI - A good-continuation model of some occlusion phenomena. AB - Occlusion phenomena raise two questions: (1) When will an occluding and a partly occluded object be seen, as opposed to several nonoverlapping objects? (2) What is seen behind the occluding object? Available theories give no satisfactory description of occlusion data. In our view, this situation is at least partially due to the fact that patterns used in occlusion studies are always regular, whereas it is almost unknown which regularities are actually perceived in occlusion patterns. We have therefore collected a complete set of data for a restricted domain of patterns with minimal regularity. Starting from these data, we have developed a model of the perceptual organization of this class of patterns and tested it in a second experiment. The model is a specification of the Gestalt law of good continuation. It assumes that there is a tendency to describe a pattern by the smallest possible number of contour elements and with the smallest possible changes of direction within and between necessary contour elements. The results fit in well with the predictions of the model. It is further demonstrated that the model also describes the preferred interpretations of many regular patterns, published in other studies. PMID- 1494612 TI - A critical discussion of Kellman and Shipley's (1991) theory of occlusion phenomena. AB - Kellman and Shipley (1991) recently advanced a new theory to explain the perception of partly occluded objects and illusory figures. The theory is a formalization of the Gestalt law of good continuation. In this paper we describe their account of occlusion when the contour of the occluder is completely specified by a display. Next, we outline some critical objections and present a number of counterexamples. Finally, we compare their theory with Wouterlood and Boselie's (in this issue) model of occlusion phenomena, which might also be considered as a formalization of the law of good continuation. PMID- 1494614 TI - [Single case analytic evaluation of inpatient psychotherapy in a patient with ulcerative colitis]. AB - This study outlines a practicable empirical method for the process-accompanying evaluation of the in-patient treatment-process. On the example of an integrative conceptualized psychoanalytic oriented therapy model for psychosomatic patients the treatment-process of a patient with ulcerative colitis is studied. PMID- 1494613 TI - [Functional stomach and intestinal complaints in young adults: incidence, follow up, personality and psychosocial factors]. AB - The prevalence rates and the course of functional gastrointestinal disorders in addition to psychopathology and psychosocial factors which are assumed to be associated with functional disorders were longitudinally investigated in an epidemiological cohort study of young adults aged 21-30 from the Canton of Zurich (Switzerland), by means of four interviews. Case definition was based on operational criteria concerning frequency and duration of symptoms reported by the subjects. One-year prevalence rates of (functional) stomach complaints and intestinal complaints were found to vary between 8.7 and 12.7 percent, and 9.1 and 11.1 percent, respectively, depending an the year of the interview. Subjects with stomach complaints scored higher on depression, anxiety and hostility (Hopkins Symptom Check List, Freiburger Personlichkeitsinventar) then the controls. These associations were less strong among subjects with intestinal complaints. In addition, both complaints were found to be associated with scores on a life events measure, with distress from the social network, and with lack of social support. PMID- 1494615 TI - [Participation refusal by probands in an epidemiologic long-term study- sociodemographic, clinical and psychometric findings]. AB - Usually little is known about probands who participated in an epidemiological longitudinal field survey but refused participation in follow-up investigations. For reasons of data protection and on account of the fact that investigative instruments used in longterm field surveys or panel studies are more focused on well defined issues (opinions, attitudes, assessment of behaviors) and less on personality variables, differentiated statements on probands who explicitly refused cooperation can hardly be made. In our epidemiological longitudinal field study on prevalence and course of psychogenic disorders we have a different situation. Within the limits of our study we had the unique opportunity to gain far-reaching information on probands who refused to participate in preceding investigations in regard to sociodemographic, psychometric and clinical variables. The clientele of refusers we present in our paper mainly comprises elderly, married, rather obsessive-compulsive structured, lower-class females. According to our data interactive aspects are equally responsible for reduced cooperativeness. The significance of our findings for the planning and carrying out of epidemiological longitudinal field surveys is discussed. PMID- 1494616 TI - [Psychosomatic medicine between natural science and psychological science- tertium non datur?]. AB - Psyche and soma are open to scientific-causal analysis for biomedicine as well as for social-empirical studies. Both are furthermore accessible to the ideographic discourse of subjective meanings and intentional acts. The German language marks this difference with the terms of "Korper" (body) and "Leib" (embodied soul- spirited body). The Bieri-trilemma demonstrates the resulting epistemological calamity. Neither the so-called behavioral medicine as variation of an ontologic methodological materialism nor pure phenomenology of the sick subject lead the way out of such inconsistencies. Attempts of systemtheoretical mediation usually only prove their poor reviewing of traditional discussion. This paper outlines some of the currently interesting positions towards the so-called body-soul problem in the field of psychosomatic medicine, at the same time warning against hasty expectations. We discuss the intentional-biographic approach, the biomedical approach (including the simultaneity correlation (Schultz-Hencke) as well as the brain-soul-correlationism (Kurthen and Linke). As our result we maintain the complementarity of a double discourse for psychosomatic medicine, namely the complementarity of hermeneutic analysis of meaningful processes and of bio-psycho-social casualties. The complementary discourse levels occasionally find their counterparts on an intersubjective-objective time-space-axis. For this we suggest the concept of socialempiric and biomedical markers. Attempts of mediation, be it from systemic-emergence-theoretical or from hermeneutic perspective of interaction forms and their interaction engrams corresponding to their central nervous substratum, turn out to be mystifications of actual incompatibilities, namely of the inevitably double discourse. For this the theory of absolute processes (W. Sellars) promises mediation, but so far no more.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1494617 TI - [Emotional helplessness--a risk factor for somatic diseases]. AB - The purpose of this paper is to summarize some findings concerning the relationship between an inability to cope with emotions. Typ A behavior and somatic diseases. Based on those findings it was suggested that different concepts of behavioral medicine may share the similar psychological basis, and an inability to cope with emotions might be a very important characteristic to link those behavioral manifestations. PMID- 1494618 TI - [Psychological symptoms after immigration: a comparison of various groups of immigrants in Berlin]. AB - In a postal questionnaire we examined three samples of persons seven and a half months after their migration to Berlin: 1. 512 people having left East Germany, 2. 90 Germans who had left Poland, and 3. 283 people who lived in western parts of Germany before. The present study was to investigate social integration and psychic complaints in these groups. In general, all groups reported increased frequencies of unspecific symptoms like inner restlessness, irritability, nervousness, rumination, and sleeplessness. In people from the GDR symptoms decreased significantly during the first seven months after migration. Symptoms of people who had come from western parts of Germany increased within this period. Generally the course of symptoms was more favorable, when people found a satisfactory job. PMID- 1494619 TI - [Hospital care versus home nursing: on the quality of life of terminal tumor patients]. AB - The present study investigated quality of life in 41 terminally ill cancer patients. Twenty-one of them received hospital care, 20 home-bound hospice care. These groups were comparable with respect to the patients' physical condition. The following variables were chosen as indicators of quality of life: perceived social support and social distress, coping with illness, perceived positive environmental factors, perceived control over daily activities and caring routines, contentedness with medical care and nursing, physical well-being. Assessment was made by means of a semi-structured interview. The data indicate that the home-bound care was superior with respect to the following variables: perceived positive environmental factors, perceived control over daily activities and caring routines, and contentedness with nursing. No differences between groups were found for any of the other variables. PMID- 1494620 TI - [The psychodynamic aspects of suicidal behavior]. AB - The psychodynamic basis of suicidal behavior is investigated from the standpoint of the psychology of drive, ego, object relations, and self. Each of these four perspectives helps us understand the different aspects of suicidal behavior, the psychodynamics of which cannot be formulated in terms of a unique generally valid and all encompassing concept. The high degree of aggressive potential, the ocnophile personality and the pronounced narcissistic vulnerability appear as central conceptions regarding suicidal behavior. PMID- 1494621 TI - [Meditative stress coping program with psychosomatic patients]. AB - A stress management training for ambulant psychosomatic patients has been developed. Essential parts of the intervention are meditative body relaxation (Kum Nye) and meditative cognitive restructuring. The training has been applied to psychosomatic patients with various kinds of diagnosis in a total of 14 group sessions. The following indicators of therapy success have been assessed: Positive and negative self-communication, positive and negative emotionality, depression, bodily complaints, number of days with bodily complaints and 12 coping scales. Results are reported in agglomerated single case judgements. In the intervention group 55% of the participants showed improvements vs. 14% in the waiting-list-control group. The significant results are appraised as clinically not fully satisfying; possible improvements of the intervention are discussed. Hints to a contraindication with abdominal complaints are given. PMID- 1494622 TI - [Lay etiologic theories and coping with illness in severe physical diseases. An empirical comparative study of female myocardial infarct, cancer, dialysis and multiple sclerosis patients]. AB - In a multicenter approach 451 female patients, suffering from severe somatic diseases, were investigated on strains, disease-related attributions, coping and quality of life. Four diagnostic groups were involved, myocardial infarction (MI), Cancer (CA), end-stage renal disease (ESRD), and multiple sclerosis (MS). With respect to coping with the onset of illness or the diagnosis, all four groups accordingly reported placing trust in the doctors, compliance-related strategies, fighting spirit and information seeking as most markedly applied coping modes. But in each group a different predominant causal attribution of the disease was found, heredity in the MS-, pollution in the cancer, stress in the MI and iatrogenic factors in the ESRD-group. The main influencing factors on the future course of the disease accordingly in all groups were "progress of medicine" and internal cognitive and behavioral factors. After statistical control of age, education, and duration of illness only the score "depressive coping" discriminated between the groups (MS-patients with highest, MI-patients with lowest scores). With respect to life satisfaction, MI- and cancer patients together formed a cluster with higher and ESRD- and MS-patients one with lower satisfaction. Cancer- and MS-patients considered fighting spirit as "most helpful" coping mode, while MI-patients favoured placing trust in the doctors and information seeking. Religion was found as second or third helpful coping mode. PMID- 1494623 TI - [Psychodynamic aspects of coping with illness in stroke--experiences with a psychotherapy group]. AB - The authors describe their experience of a group--psychotherapy with stroke patients during the phase of inpatient neurological rehabilitation. The process of coping in stroke patients shows similarities with grief reactions following the loss of important objects. But it is usually complicated by the fact that the physical injury is experienced as a narcissistic trauma resulting in low self- esteem and in feelings of anger and despair. Psychotherapeutic interventions can help to deal with such negative affects and should facilitate a mourning process, which is inevitable if adaptation to a life with a physical handicap should succeed. PMID- 1494624 TI - [Stages of grief in coping with diabetes?]. AB - Forms of coping with diabetes were determined on the basis of self-ratings of emotions (depressive, sad, angry, anxious) and responses on a 30-item "stages of grief" questionnaire by 52 inpatients aged between 25 and 50 (diabetes duration 1 to 35 years) at the beginning of a 12 day diabetes education program. Psychometric qualities of the instruments were evaluated. To test empirically the notion of grief stages in coping with diabetes, the frequency of emphasis on one or more emotional areas or stages of grief was determined and tested to ascertain whether various conditions occurred more frequently than was expected by chance. Results indicated that shortly after diabetes manifestation scores on protest and depression with respect to diabetes were elevated. The majority of cases could not be assigned to a single emotion or stage of grief but displayed negative emotional reactions in different content areas simultaneously. Consequently the concept of grief stages for coping with diabetes as well as recommendations based on this concept are questioned. PMID- 1494625 TI - [Affective-cognitive coping with attacks and illness behavior in patients with bronchial asthma]. AB - The purpose of this study was to investigate attack-related cognitive coping styles in 80 patients with bronchial asthma and to relate them to outcome parameters of illness behaviour. All patients had participated in a 5-day-lasting asthma treatment and teaching programme (ATTP). Outcome variables to be predicted were: The number of days in hospital due to asthma during the year following the training programme and the patients' adherence to the recommendations of the programme one year later. Independent predictor variables were: pre-training attack frequency, hospitalization due to asthma, medication intensity, pulmonary function, asthma symptom anxiety, trait anxiety and attack-related cognitive coping styles. Multiple regression analyses show the importance of a "minimizing/self-confident" coping style in predicting days in hospital, while a "diverting" style predicts best a poor management of attacks in patients on oral steroids. PMID- 1494626 TI - [The Giessen Symptom Questionnaire for children and adolescents]. AB - The Giessen Subjective Complaints List for children (GSCL-C) a questionnaire on physical complaints in self-image form, was developed out of the adult GSCL. The questionnaire contains items from the areas; general wellbeing, vegetative complaints, pains, emotionality and children's complaints. The subject is asked to estimate the degree of distress caused by each complaint (never/rarely/sometimes/often/always). Factor analysis based on a sample of 1047 schoolchildren aged 9 to 15 revealed five complaint complexes containing seven items each, which were subsequently grouped into the following scales: (1) Exhaustion, (2) Gastric Complaints, (3) Pains in Limbs, (4) Circulatory Problems, (5) Cold Symptoms. The sum of the five scales makes up the sixth scale score, overall distress. Besides describing the development of the instrument and its scales, sex- and age-related norms are given and the assessment criteria explained. Procedure and areas of application are also discussed. PMID- 1494627 TI - [Therapeutic factors in psychoanalytic-interactional and depth psychology founded group therapy: an empirical study]. AB - Depth psychology based and psychoanalytic-interactional group therapy were compared with respect to their therapeutic factors. The comparison was performed in patient groups by using a questionnaire asking for the occurrence and helpfulness of specific behaviour of the therapist and of experiences in the group. About 200 questionnaires for each method were analyzed. It could be shown that (1) discrimination between the methods was more marked concerning therapist's behaviour than experiences with the other group members, (2) that the obtained unspecific factors correspond to results in the literature on group and individual therapy and (3) that those items about the therapists behaviour claimed to be specific for each method did not discriminate these methods in the expected direction. PMID- 1494628 TI - [Differential indications for ambulatory group therapy of obesity--exemplified by "interdisciplinary therapy of obesity"]. AB - The article deals with reflections about the differential indication for out patient group therapy treatment of patients suffering from a considerable overweight by the example of the "Interdisciplinary therapy of obesity". First the conception of the "Interdisciplinary therapy of obesity" is presented. Within the context of evaluation of the therapy program, especially the results of a long-term follow-up study and the special conditions for severely obese people are dealt with. Empirical results and clinical experiences build the foundations to work out differential indication criteria like therapy motivation, degree of overweight and degree of psychological strain. On this basis modifications of the therapy program are suggested in the form of three different kinds of treatment, taking into account the clinically different groups of obese people. PMID- 1494629 TI - [Affective experience in the group process and therapeutic outcome]. AB - In this investigation is reported about measurement of affective behavior and feelings during the process of group psychotherapy. Therefore a cluster analysis of 4 parameters about 5 group sessions and 9 members and the group as a whole was made. The hypothesia were that effective feelings concern the group as a whole, that they were changing during the process and that they concern the individual process. It could be shown that in common there was a connection between individual process of affective behavior and outcome. Questions which came from differences of these results concerned the problem of characterizing exactly what going on related changing of attitudes and in which manner we can understand outcome. PMID- 1494630 TI - [Therapy dropouts in closed groups]. AB - Drop-outs in group psychotherapy are an everyday clinical problem. A premature quitting by one patient may have great consequences, especially in closed groups, not only for the drop-out but also for the remaining group members. Compared to the clinical relevance, empirical research on the conditions leading to a premature termination is quite meagre. Empirical basis of the study presented here are 58 groups with a total of 445 patients with a variety of symptoms and personality structures. All groups started with a 3 month inpatient period and were continued as a closed outpatient group for about 2 years. 110 patients (24.7%) left the group at least 3 months before the agreed end of the group. Empirical research on conditions leading to the premature drop-out is based on three perspectives: 1. patient-oriented: The values of certain patient variables e.g. symptoms, personality structure, socio-economic status etc. are considered as potential predictors. 2. institution-oriented: Here group characteristics are considered as the pool of potential predictors: e.g. group size, decisions made under time pressure, cotherapy etc. 3. group-oriented: The values of patient variables for one patient in relation to other group members (e.g. "isolated position") is considered here. From each perspective we were able to find potential relevant predictors. PMID- 1494631 TI - [Promoting research in the area of psychosomatic medicine]. PMID- 1494632 TI - [Psychoanalytically oriented group therapy with psychogenic pain patients. A contribution to the treatment method]. AB - Psychoanalytically oriented therapies are widespread in the treatment of chronic pain patients in Germany but there are still few evaluation studies especially for long-term therapies. Derived from the therapy process of a homogenous pain group and its evaluation modifications from the usual psychoanalytical group therapy method necessary for pain patients are outlined. PMID- 1494633 TI - [Therapeutic factors of inpatient analytic group psychotherapy]. AB - Several change mechanisms, their interrelationship, and their relation to outcome as well as to long-term follow-ups have been investigated in an inpatient group therapy. Eight of initially ten patients finished a long-term group in an inpatient setting for severe neurotics and personality disorders. Successful patients were able to change significant behavior characteristics, to develop a higher cohesiveness towards the group and especially to use aspects of family reenactment in order to change internalized significant object representations. The results indicate that important changes occur early during the treatment. The contributing change mechanisms and their interdependency are described and discussed in detail. PMID- 1494634 TI - [Phases in the rehabilitation of male and female bone marrow transplant patients]. AB - Teamwork is essential when investigating the long-term adoption of such medical intervention that are highly demanding on patients, physicians and nursing staff. Bone marrow transplantation represent such an intervention for a series of well defined hematological diseases. The contribution demonstrates the multiple perspective approach of the Ulm team. A case report illustrates the multiplicity of clinical issues. The state of research allows the sketching of a process model on rehabilitation. PMID- 1494635 TI - [Psychosomatic determinants of graphospasm]. AB - As there is a variety of psychic and somatic variables in its genesis, the writer's cramp could be a syndrome of different subtypes. Therefore 62 former psychotherapy-patients with writer's cramp were examined according to a design of several dimensions in order to find out if there were any subtypes. The parts of the examination were exploration, structural interview, neurological examination, psychological examination of the personality, examination of some electrolytes in serum and radiograph of neck spinal column. Different multivariate statistical methods isolated two subtypes of patients with writer's cramp. The first group comprises patients with fine and/or big dysfunctions of motor activity, the symptoms are independent of psychic factors or of psychotherapy. The second group is characterized of a monosymtomatic writer's cramp, of a neurosis and of remissions of motoric symptoms following psychotherapy. The examination shows that fine and/or big dysfunctions of motor activity which often co-occur the writer's cramp are important criteria for differential diagnosis and indications. PMID- 1494636 TI - [Effectiveness of psychosocial management of cancer patients--a critical review of empirical studies (status: December 1990)]. AB - 41 empirical studies evaluating psychosocial care of cancer patients, published between 1975 and 1990 are presented. Only those studies were selected that examined adult patients and controlled the effects of psychotherapeutic interventions. 35 studies reported significant effects on coping, mood states or quality of life. 6 articles were inquiries into the efficiency of intervention on time of survival, 3 measured the impact on the immune system. PMID- 1494637 TI - [Preliminary comments on existential analytic psychosomatic medicine]. AB - Existential analysis as a personal and meaning orientated psychotherapy describes a person in the performance of its existence. The anthropological and therapeutic concept of the existential analysis are presented in essential points (intentionality, self-transcendence, will to meaning, ability of self-detachment, corporability and responsibility) as a way of approach and interpretation. Psychosomatic illness is understood as a mode of personal existence. The integral "gestalt" of a person in its subjectivity, biography and corporality is reflected on with regard to its abilities and revealing of individual possibilities of meaning. The under determination of psychosomatic phenomena shows itself as an expression of a person's relative freedom to decide about its own development. PMID- 1494638 TI - [The benign chronic pain syndrome. Diagnostic subgroups, screening parameters, biographical disposition]. AB - The concept that all pain must have an organic cause if not the pain is not real, is still very common in medical practice. For chronic pain this leads to big costs by repeated technical examinations and often even to iatrogenic injury to the patient as a result of diagnostic or therapeutic interventions. Psychogenic pain patients are particularly afflicted by this process of chronification. The results of a study investigating 151 chronic patients show, that psychogenic pain patients (PP, n = 75) are significantly different from those whose pain was caused by organic factors (OP, n = 35) regarding their development in childhood and adolescence (in the sense of a marked emotional deprivation). Including additional parameters raised by a structured interview (SBAS) and the trait-score of the STAI an identification of PS is possible with high sensitivity and specificity (about 95 percent). By the aid of the maturity of defence mechanisms three taxonomic subgroups in PP can be differentiated (type A, B, C). Between these types there are significant differences regarding illness behaviour (e.g. medication abuse, "doctor shopping") and responsiveness to a psychological pain interpretation. The results confirm the necessity of a differentiation of chronic pain patients as to the etiology and pathogenesis and furnish even the physician without psychosomatic education with diagnostic criteria relatively simple to raise. By these criteria a prevention of chronification in a lot of pain patients is possible. Derived from the results a pathogenic model for psychogenic pain is developed. PMID- 1494639 TI - [Familial and pain-related markers from the viewpoint of chronic pain patients and their partners]. AB - Based on a general family model Saile and Schmitz (1991) developed the Pain related inventory of family adaptability and cohesion (SIFAK), which assesses three aspects of family life related to chronic pain: adaptability in dealing with chronic pain, pain related enmeshment and pain related disengagement and alienation. 40 patients with chronic low back pain and their spouses completed a revised version of the SIFAK and measures of pain intensity, pain related disability and marital satisfaction. Patients and spouses agreed more on marital satisfaction than on pain related variables. In multiple regression analyses marital satisfaction and pain related disability--each in the view of patients and spouses--were predicted by pain and family related variables. Implications for future research (other data sources, other measurement methods) and for psychological treatment of chronic pain are discussed. PMID- 1494640 TI - [Early risk factors in schizoid, neurotic and healthy probands]. AB - The following results were obtained on comparing the genesis of schizoid, neurotic and healthy subjects: 1. The schizoid patients examined by us had experienced a greater total risk-associated stress during childhood and adolescence than the comparative groups. 2. Special risk-associated stress is due to: a) a stress-burdened family atmosphere (laden with conflicts within the family and burdened with diseases), b) stress originating from the mother (risks of old age and diseases), c) stress originating from siblings (large number of siblings, smaller age intervals, etc.), d) stress originating from the parents' low standard of education. 3. Schizoids can be separated from healthy subjects on the basis of the childhood risks assessed above. 4. Schizoids cannot be separated from the group of neurotics by the characteristics listed here. These are not schizoid specific risks but factors of general stress. 5. Marked sex-specific peculiarities were seen. a) These point to a higher degree of diagnostic separation between schizoid and neurotic men than between schizoid and neurotic women. b) Schizoid women cannot be distinguished from neurotic women on the basis of the criteria of genesis covered by our study. c) Schizoid men are easily separated from the two other groups of men. This is mainly due to a genesis of an instability of reference. This, therefore, appears as a genuine schizoid risk. PMID- 1494641 TI - [Developmental structures in children with perinatal risk factors]. AB - This longitudinal study focuses on the improvement of understanding the development of infants with perinatal complications. 38 infants with perinatal complications requiring intensive care for at least two weeks and their parents were examined shortly after birth and up to the age of 3 years. A number of biological and psychosocial data were collected. By means of cluster analysis based on data collected from children and families during the first three month three groups were obtained. After three years, children differed significantly in many developmental areas according to this grouping. A second cluster analysis based on three years follow-up data yielded four clusters which were characteristically related to the original ones. The results are discussed using a transactional perspective. PMID- 1494642 TI - [Individual immunological parameters in clean-up team members and patients with sequelae of acute radiation sickness 5 years after the effects of the Chernobyl accident]. AB - A study was made of deviations, beyond 1 sigma and 1.5 sigma of a mean value (M) of a donor group, in individual immunological parameters (for instance, the number of CD5+, CD2+, CD4+, CD8+, CD25+ and B-cells; alpha 1-thymosin concentration; and autoantibody titers to antigens of epithelial reticulum cell cytoplasm) in patients suffered acute radiation sickness (ARS) and liquidators of Chernobyl NPP accident. The radiation damage to the immune system was reliably detected in the affected subjects examined: they exhibited a decrease in the alpha 1-thymosin level below M = -1.5 sigma and in absolute B cellularity below M = -1 sigma; and increase in the number of CD25+ cells and in the level of serum autoantibodies to antigens of thymus epithelial reticulum cell cytoplasm. When several parameters selected were examined simultaneously the frequency of recording the deviations in merely one of them markedly increased. PMID- 1494643 TI - [Expression of ORIGIN-like sequence in mammalian cells]. AB - There are some genes whose expression increases in non-proliferating hepatocytes after whole-body X-irradiation. We suppose that some of them participate in cell division regulation. To verify our postulate we have studied expression of autonomously replicating sequence pDARC1 in normal, irradiated and dividing rat hepatocytes. We have succeeded earlier in cloning the autonomously replicating sequence pDARC1 and have shown that it could be transcribed in X-irradiated hepatocytes. Here we report on the results of analysis of this sequence expression in dividing mammalian cells. Hybridization with the pDARC1 sequence reveals 4.0 kb mRNA in non-proliferating rat hepatocytes after X-irradiation: this mRNA is absent in normal hepatocytes. Induction of 4.0 kb mRNA is a function of radiation dose; 4.0 kb mRNA content is maximum 6-24 h following whole-body 6 Gy X-irradiation. The 4.0 kb mRNA is also found in dividing rat hepatocytes during the pre-replicative period. PMID- 1494644 TI - [Identification of a multihit model for nonhomogeneous cell population]. AB - A generalized multihit-multitarget model for a nonhomogeneous, with respect to radiosensitivity, population of irradiated cells is presented. The least squares and the maximum likelihood estimation of the model parameters is given. The estimates quality is evaluated by the computer-based study. The results obtained show the possibility of the parametric identification of cell radiosensitivity distribution according to the "dose-response" data. PMID- 1494645 TI - [Characteristics of the effect of irradiation at different dose rates on survival, death kinetics and response of critical systems of the C57Bl/6 mice]. AB - A comparison was made of the biological effect on mice of irradiation at different dose rates (70, 5.5 and 1.5 cGy/min) with equally effective, with respect to lethality, doses, or with physically equal doses within the range from 1/4 of LD50/30 to LD99-95/30. Equally effective, with respect to lethality, doses caused similar changes in the intestinal epithelium and in the haemopoietic system. The death rate kinetics was identical with doses of LD80-95/30 within the dose-rate range under study. The equally effective doses caused injuries, different in degrees, to critical systems, including CFUs. PMID- 1494646 TI - [Effects of single gamma-irradiation on the activity of ornithine decarboxylase in the thymus and pulmonary tissue]. AB - In studying the dose (0.1-6 Gy) and time (2 h to 180 days) dependence of ornithine decarboxylase activity, it was found that deviations from the control were more pronounced in the thymus than in the pulmonary tissue. The radiation effect was a function of dose and time after irradiation. A nonmonotonous type of the dose-response curve was observed 7 days after irradiation: the radiation effect with a low dose (0.1 Gy) was opposite to that with sublethal doses (1-6 Gy). PMID- 1494647 TI - [Effects of irradiation on fatty acid structure of membrane lipids of the sarcoplasmic reticulum]. AB - It has been shown that single local X-irradiation (0.21 C/kg) of the rabbit hind limb in the early period of acute radiation injury (1 and 14 h) causes a decrease in saturation of sarcoplasmic reticulum membrane lipids. It is mainly connected with a decreased saturation of the total fraction of phosphatidyl serine, phosphatidyl inositol and phosphatidyl choline. The above changes can increase permeability of the sarcoplasmic reticulum membranes for Ca(2+)-ion after X irradiation. PMID- 1494648 TI - [Isoenzyme spectrum of lactate dehydrogenase, malate dehydrogenase, esterase and acid phosphatase of rat brain cells at different times after external 1 Gy gamma irradiation]. AB - The influence of external single gamma-irradiation with a dose of 1 Gy on the isoenzyme composition of lactate dehydrogenase, malate dehydrogenase, esterase and acid phosphatase in the cytoplasm of rat brain cells has been investigated. Irradiation was shown to cause differently directed changes in the ratio of the isoenzymes under study at different times after exposure. The isoenzyme spectrum of lactate dehydrogenase and malate dehydrogenase was shown to be normalized on day 30 after irradiation, whereas the isoform composition of esterase and acid phosphatase was not stabilized at that time. PMID- 1494649 TI - [Early changes in intracellular ATP concentration after 5 Gy irradiation by routine regimen and regimen modified by low doses (0.1+4.9 Gy)]. AB - Comparative studies were made of immediate (within the first minutes) changes in intracellular ATP concentration after irradiation by different regimens. ATP concentration in cells at a stationary phase of growth increased immediately after irradiation with a dose of 5 Gy, reaching its maximum within 30-40 min. Irradiation with the same total dose, by the regimen of 0.1 + 4.9 Gy at a 3 minute interval between the doses, did not cause alterations in the ATP content in cells. It is concluded that the absence of the increase in the parameter under study (ATP) after irradiation by the latter regimen indicates that preirradiation at a dose of 0.1 Gy inhibits the adequate development of an early response to irradiation with a dose of 4.9 Gy. PMID- 1494650 TI - [The mechanism of action of low doses of gamma radiation connected with the development of human cell resistance to mutagens]. AB - The human fibroblasts were gamma-irradiated with low doses (0.07-0.21 Gy). After a short time interval (3 h), a study was made of the postirradiation viability of cells (by the trypan blue dye exclusion method); post-N-methyl-N'-nitro nitrosoguanidine-DNA synthesis (by 3H-thymidine incorporation immediately after the mutagen treatment) and postirradiation induction of DNA single-strand breaks (by alkaline elution of cells lysed on the membrane filters). The preirradiation of cells with low doses of gamma-rays was shown to render the cells resistance to induction of DNA breaks by the following exposure to gamma-radiation. The survival rate increased; DNA synthesis was resistant to alkylation damage in these cells, as compared to nonirradiated cells. PMID- 1494651 TI - [Effects of chronic gamma irradiation on the activity of adenylate cyclase in rat lung tissue]. AB - Different phase changes were observed in adenylate cyclase (AC) activity of pulmonary tissue plasma membranes under chronic gamma-irradiation of rats at a dose-rate of 12.9 cGy/day. Comparison of AC basal activity with the data reported earlier on changes in ornithine decarboxylase activity under similar radiation conditions showed unidirectional changes which indicated that cAMP-dependent processes were possibly involved in radiation modification of ornithine decarboxylase. PMID- 1494652 TI - [Does ionizing radiation induce an adaptive response in mouse L5178Y lymphoma cells?]. AB - Growth kinetics of LY-S and LY-R cells (radiosensitive and radioresistant sublines of murine lymphoma L5178Y) has been investigated after beta-irradiation at cumulative doses of 1.5 to 20 cGy and dose rates of 0.8-10 mGy/h. It has been found that after 48 h culture in a complete medium the number of cells differed 5 times, whereas after X- and gamma-irradiation, Do values differed 1.62 times. Using the growth rate as the end point in evaluating the combined effect of beta irradiation (10 cGy) and subsequent X-irradiation with lethal doses, we observed an increased relative cell number, in comparison to that after X-irradiation alone (an "adaptive response", using this criterion), in LY-S cells irradiated with a dose of 2 Gy. In contrast, when reproductive death of LY-S and LY-R cells the end-point analyzed, the lethal effect of consecutive beta- and X-irradiation in LY-S cells was higher than that expected for X-radiation alone (the synergistic effect). PMID- 1494653 TI - [Radiosensitivity of cells-precursors of hemopoietic stroma (CFU-F) in the rat bone marrow under the effect of 60Co gamma irradiation in various conditions]. AB - Conditions have been developed for cloning cells-precursors of rat bone marrow haemopoietic stroma, that form in culture dense and sparse fibroblast colonies (CFU-F) at a plating efficiency of 10(-4). Radiosensitivity of rat bone marrow CFU-F, with 60Co-gamma-irradiation in vitro, is characterized by the values of Do and n of 1.87 Gy and 1.4 respectively for all clones; 0.65 Gy and 6.7 for dense clones, and 4.27 Gy and 1.0 for sparse clones. This confirms the observed heterogeneity of CFU-F population consisting of highly radiosensitive and radioresistant subpopulations. The parameters of rat bone marrow CFU-F are nearly the same with irradiation both in vivo and in vitro; with in situ irradiation, the oxygen effect comes into play in a radiosensitive subpopulation of CFU-F; the OER values are 1.6, 2.6 and 0.9 for all, dense and sparse clones respectively. PMID- 1494655 TI - [Postradiation recovery of hemopoietic and stromal precursor cells in mice preinjected with prodigiozan]. AB - Injection of prodigiozan to mice 24 h before irradiation caused, by the time of the radiation effect, a decrease in the number of haemopoietic cells-precursors (CFUs and CFU-HM) in the bone marrow and an increase in the functional activity of stromal cell-precursors--the haemopoietic microenvironment of transfer units (HMTU); in the spleen, the number of CFUs decreased, but the number of CFU-HM increased considerably. During the postirradiation period, the haemopoietic and stromal precursors were damaged to a lesser extent, and CFUs, CFU-HM and HMTU recovered more readily in prodigiozan-protected animals than in unprotected mice; the HMTU restoration preceded the increase in CFUs and CFU-HM levels. PMID- 1494654 TI - [Incidence of the development of 90Sr-induced osteosarcomas depending on the age of the animals]. AB - In experiments with albino male rats, a study was made of the influence of age on the incidence of osteosarcomas induced by 90Sr. It was shown that the incidence of tumors decreases exponentially with age. PMID- 1494656 TI - [Changes in the sensitivity of mice to the action of gamma irradiation by Viscum album L. polysaccharides]. AB - The influence of water-soluble polysaccharides of Viscum album L. on the survival of mice subjected to whole-body gamma-irradiation has been investigated. Polysaccharides were shown to exert a radioprotective effect which was a function of both the radiation dose and the drug dose and time of its injection. The maximum radioprotective efficacy of polysaccharides was observed after their injection 15 min before irradiation. A single intraperitoneal administration of polysaccharides (25 mg/kg) before irradiation with LD50/30 and LD100/10-12 increased the 60-day survival rate up to 95% and 27% respectively. The postirradiation injection of polysaccharides prevented death of 80% of mice given LD50 and increased the average life expectancy of animals irradiated with absolutely lethal doses. PMID- 1494657 TI - [Effects of dalargin on reparative processes in skin and muscle wounds of irradiated animals]. PMID- 1494658 TI - [Comparative analysis of mechanisms of the modification of microorganism viability under the effect of UHF heating and hyperthermia]. AB - In experiments with models of isogenic Escherichia coli strains, a comparative study was made of the effect of SHF of electromagnetic field and hyperthermia. The survival rate of bacteria was determined and, simultaneously, injuries to genetic supramolecular structures were registered through measuring the anomalous time dependence of cell lysate viscosity. The combined effects of the mixture of these factors with H2O2 microconcentrations were studied. The differences observed in their realization were attributed to the different mechanisms of action of these factors on the repair enzyme systems of the studied cells. It has been found that the effect of microwaves on microorganisms causes much severer damages to DNA that hyperthermia does. PMID- 1494659 TI - [Effects of a medium pH on the ability of Chinese hamster cells to repair radiation injuries]. AB - In experiments with Chinese hamster cells at exponential and stationary growth phases, it has been shown that the postirradiation incubation of irradiated cells in a medium with low pH (up to 6.0) promotes the recovery of cells from potentially lethal damages; it has also been found that the recovery from sublethal radiation damages does not depend on the medium pH. The long-term incubation of nonirradiated cells with low pHc causes death of part of cells. PMID- 1494660 TI - [Effects of fungal mycelium extracts on 137Cs accumulation in human embryo cells]. AB - The method is proposed for primary evaluation of the ability of drugs of various genesis to affect the accumulation of radionuclides in cells. Extracts of mycelium of wood-rotting Basidiomycetes were shown to prevent 137Cs accumulation in cultures of human embryo fibroblast. PMID- 1494661 TI - [Choice of quantitative characteristics of a radiation modifier affinity and the range of its pharmacological action (minireview)]. AB - On the basis of the literature the necessity of using not only DMF and maximal protective or sensitizing effects, but also the affinity and the range of the pharmacological action of radiation modifiers is argued. The affinity is worth while to expressed as ED50 (the dose that produces a half of the maximal effect), and the range of the pharmacological action as a therapeutic index K = LD50/ED50. PMID- 1494662 TI - Failure to monitor FHR: catastrophic results. PMID- 1494663 TI - "No independent recollection": blockbuster damages. Case in point: Atkins v. Lee (603 So. 2d 937-AL [1992]). PMID- 1494664 TI - MT: Conviction of sex assaults: revocation of expired license upheld. MI: Physician referral to acupuncturist: nurse's illegal practice of medicine. PMID- 1494665 TI - Plastic cup on i.v. site: nurse-expert testimony. Case in point: Morris v. Children's Hospital Medical Center (596 N.E. 2d 1110-OH [1992]). PMID- 1494666 TI - [A rightful tribute to a precursor in bioimaging: Christian Andreas Doppler]. PMID- 1494668 TI - [Angiography with magnetic resonance]. PMID- 1494667 TI - [Characterization of benign focal hepatic lesions with magnetic resonance]. PMID- 1494669 TI - [Vascular radiology and physics of fluids]. AB - In the cardiovascular system, morphology and functionality are closely related. The observation that atherosclerotic lesions appear with different incidence in the various sites and prefer bifurcations, suggested that vascular architecture might be an important pathogenic factor. Vascular geometry deals with the evaluation of the "form" element from a theoretical point of a view, pointing out the angles and diameters which can make the arterial system physiologically more efficient. The key element of the system is the bifurcation: depending on whether bifurcations are considered as a single entity or as a whole, either "local" or "global" geometry is employed. The morphology of the bifurcation directly affects blood flow patterns, influencing both blood flow velocity and wall shear stress. Experimental studies evidenced that high blood flow velocities and low wall shear stress have, respectively, a preventive or favorable role in atheroma development. By observing these altered flow sites, the areas which are most likely to develop atherosclerotic damage have been detected in the various bifurcations; the areas correspond to angiographic and autoptic findings. Based on their experience, the authors discuss the contribution that the different imaging techniques can give to the study of vascular geometry. PMID- 1494670 TI - [Computerized tomography and conventional radiography in the diagnosis of destructive spondyloarthropathy. Our experience with 30 patients undergoing periodic hemodialysis]. AB - Thirty patients of both sexes (15 males and 15 females) with chronic renal failure who had under gone hemodialysis for 2-184 months (mean 45.1 months) were examined with conventional radiographs of the cervical spine and thin-layer CT of C4-C5-C6 to evaluate the radiographic patterns of destructive spondyloarthropathy. The radiographic patterns obtained with conventional and CT exams were compared with one another and with clinical (carpal tunnel syndrome) and biochemical data (alkaline phosphatase, parathormon, Ca, P, Ca/P, Al, beta 2 microglobulin). DSA (erosion and narrowing of the intervertebral space, collapse of the vertebral body and erosion of the vertebral plates) was recognized in 7 patients with conventional radiographs and in 11 patients with CT thanks to greater CT capabilities to recognize minimal osteolytic lesions of the vertebral body. All the patients with destructive spondyloarthropathy had personal and hemodialysis age higher than those without destructive spondyloarthropathy: 59.3 vs 57.7 years; 49 vs 39 months. Parathormon and alkaline phosphatase were increased while beta 2-microglobulin was normal. Only 2 patients with DSA had carpal tunnel syndrome. In conclusion, CT is a valuable technique for the diagnosis of destructive spondyloarthropathy but it must be performed only after conventional radiographs of the cervical spine or in the presence of clinical signs of destructive spondyloarthropathy (parathormon and beta 2-microglobulin increased, long-term hemodialysis). PMID- 1494671 TI - [Bone mineral content measurement: reflections on the equipment]. AB - Metabolic bone disorders are extremely interesting from an epidemiological, clinical and social point of view. In particular, some of them are important for they are typical of elderly people--i.e., the portion of population which is on the increase due to the lengthening of the average life. On the other hand, thanks to the current intervention techniques, the number of chronic nephropathics (in whom metabolic bone conditions may develop) has markedly increased. Therefore, sufficiently reliable methods are needed to allow the thorough evaluation of bone mineral components. Unfortunately, these methods are only of quantitative value because they are unable to discriminate the statuses of the two essential bone components--i.e., cortex and spongiosa--; we all know that bone mineral loss can currently be quantified only when amounting to < 20% of the total value, due to the addition of the mineral contents of the two components. In this paper the authors briefly report on the noninvasive techniques currently in use for the measurement of bone mineral components, especially relative to their physical bases, the knowledge of which is essential for a correct evaluation. The authors accurately reviewed the literature data relative to the various techniques and compared the results obtained by the different authors. Thus, no personal experience is reported, since this paper is aimed at being considered as a reference mark for the reader to be helped in the choice of the equipment suiting him most. However, as to preventing metabolic osteopathies, quantitative methods cannot yield absolute data, which addresses the current research to densitometry by means of the Compton method. The latter may finally lead to the development of operative equipment allowing not only the separate measurement of cortical and spongiose values, but also the qualitative evaluation of bone status--i.e., not limited to mineral loss but including also the determination of the protein, fat and water components. PMID- 1494672 TI - [Dual-energy X-ray absorptiometry of the vertebrae: determining which vertebrae should be scanned]. AB - This study was aimed at verifying whether bone mineral density (BMD) and its loss with aging are different in the lumbar vertebrae and whether the region of interest--which is usually limited to the L2-L4 segment--may be extended to L1 L4. BMD was measured by means of dual-energy X-ray absorptiometry (Hologic QDR 1000) in 74 women, aged 37 to 78 years, not affected with any disease or subjected to any treatment known to interfere with bone metabolism. The relationship between age and BMD was expressed by the following equations for L1, L2, L3: BMD-L1 = 1181.68-7.85 x age, BDM-L2 = 1251.57-7.70 x age, BMD-L3 = 1231.66-6.57 x age, as shown by linear regression analysis. The behavior of the bone density of L4 with age appeared to be different and could not be described by linear regression curves and was therefore not comparable with that of the other vertebrae. BMD was different in the four lumbar vertebrae as shown by: a) the diversity of the intercept of the regression lines describing age-bone density relationships (F = 7.7, p < 0.001); b) the bone density of L1 being lower than the mean bone density of the L2-L4 region (p < 0.005); c) the bone density of L4 being higher than the mean bone density of the L1-L3 region (p < 0.001). In order to evaluate the effect of senile degenerative changes of the vertebrae on the relevant bone density, two groups of women were considered, according to age- i.e., pre- or iuxtamenopausal and late postmenopausal. It appeared that the BMD of L1 was always more correlated to the bone density of L2 and L3 than the BMD of L4. Our results suggest that L1 is homogeneous to the L2-L3 region, relative to both bone density and its loss with aging. Therefore, L1 should be included in the region of interest during the examination. Even though the bone mineral content of L4 and its loss with aging seem to be different, our results do not allow the exclusion of L4 from the scanned area. PMID- 1494673 TI - [Platyspondylisis+ in beta-thalassemia major]. AB - Platyspondylia was observed in 14 patients affected with thalassemia major (7 males and 7 females, age range: 10-18 years) who received an intensive transfusion regimen combined with continuous chelation therapy (desferrioxamine: 50-80 mg/kg daily). Height/width ratio was decreased at all the investigated tracts--i.e., cervical and/or dorsal and/or lumbar spine. The range of height/width ratio values was 0.41-0.55 at the 5th cervical body, 0.33-0.53 at the 8th dorsal body, 0.43-0.56 at the 12th dorsal body and 0.47-0.62 at the 2nd lumbar body. The flattening of the vertebral bodies seems to be due to the depletion of hematopoetic tissue determined by the high transfusion regimen. The reduced intramedullary pressure is thought to counteract neither weight-bearing nor other biological stresses, which might ultimately provoke the thinning of vertebral bodies. PMID- 1494674 TI - [Comparative study of echography and conventional radiology in the evaluation of the Insall-Salvati index]. AB - For the study of painful patello-femoral syndromes, the authors suggest the use of US for the evaluation of the so-called Insall-Salvati ratio--i.e., length of patellar ligament/patellar length--whose alteration is suggestive of vertical patello-femoral malalignement (patella alta and patella infera). Ten normal volunteers (20 knees) were examined by means of both US and conventional radiology, and the Insall-Salvati ratio was calculated for each knee. US and radiologic measurements were statistically compared by the correlation coefficient method: the result was 0.802. US measurements were repeated twice with 0.778 interobserver variability according to the Spearman correlation index. Based on their results, the authors conclude that, in the evaluation of the Insall-Salvati ratio, the diagnostic accuracy of US is almost the same as that of conventional radiology; the former method may even be preferred for it is a simple, quick and repeatable technique not needing ionizing radiations. PMID- 1494675 TI - [Echography in the study of lipomas of superficial soft tissues]. AB - High-resolution sonography (US) was used to evaluate 47 superficial soft tissue lipomas. Forty-one lesions were found in subcutaneous tissues and 6 in superficial muscles. The lipomas were classified by location, shape, echotexture, homogeneity and US beam attenuation values. Moreover, 21 lipomas underwent histology and histologic patterns were correlated with echogenicity. Most lesions were elongated and their greatest diameter was parallel to the skin. Eighty-four percent exhibited well-defined margins. Twenty-six percent of the lipomas were hypoechoic, 24% were isoechoic, 34% hyperechoic and 16% exhibited a mixed pattern. In 27% of cases, a hypoechoic capsule was present. Superficial soft tissue lipomas exhibit unsteady echotexture: most of them are hyperechoic. The correlation between echotexture and histology showed that no typical and steady patterns can be identified, since lipomas vary from a histologic point of view. The clinical diagnosis of superficial lipomas is based on clinical history and the palpation of a well-defined, mobile and soft superficial mass. When palpation is not diagnostic, US can be used to rule out a cyst. An elongated isoechoic or hyperechoic mass in the subcutaneous tissue should suggest a lipoma, whereas a hypoechoic mass is associated with a broader range of differential diagnoses, including malignant tumors. However, malignant masses are not likely to have an elongated or flattened shape. Even though tissue characterization is less specific with US than with CT and MRI, the former method is quick, easy and less expensive and, thanks to high-frequency transducers, is also well-suited to diagnose soft tissue lipomas. PMID- 1494676 TI - [Pulmonary tuberculosis and other mycobacterial infections in patients with AIDS]. AB - Nowadays, the acquired immune deficiency syndrome (AIDS) is most certainly the major cause of the increased incidence of tuberculosis (TBC). A total of 138 patients (pts) with AIDS were referred to the Department of Infectious Diseases of the Hospital of Pisa, 1990-1991; 14 of them (10.1%) presented pulmonary TBC. In our study, we analyzed the chest films of the latter group of patients. Based on the X-ray patterns, the findings were classified as follows: hilar lymph nodes were observed in 4 pts (28.6%), isolated lymph nodes in 2 cases; associated with parenchymal involvement in 2 pts; acute alveolar TBC was seen in 4 cases (28.6%), with escavations in 3/4 (21.4%). Linear and reticular TBC were found in 4 pts (28.6%), and miliary interstitial involvement in 1 case (7%), extrapulmonary adenopathy in 4 pts (28.6%). In 4 pts (28.6%) chest X-ray findings were negative. All pts underwent serial chest X-rays in the course of therapy. HRCT was performed in 6 patients: our results are in agreement with those reported in literature. Thus, we can conclude that the major diagnostic findings in our series were: frequent isolated involvement of hilar lymph nodes, as observed in primary TBC; the infiltrates are most frequently located in the middle and basal lobes; escavations are uncommon; pleural effusion is unusual; in some pts chest X ray findings may be negative. PMID- 1494677 TI - [High-resolution computerized tomography. Staging of lobular lesions in cystic fibrosis]. AB - Forty-four patients affected with cystic fibrosis (CF) were examined by means of high-resolution Computed Tomography (HRCT) of the chest; the sensitivity of this technique was evaluated in identifying small pulmonary structure alterations, and its role outlined. In all cases, HRCT scans allowed early lobular shape anomalies to be detected and secondary pulmonary lobular lesions to be correlated with disease evolution. A classification for lobular lesions was proposed: Stage I - Thickening of the bronchovascular bundle and/or intralobular septa and/or middle interstitial compartment. Unessential changes in lobular ventilation. Preservation of lobular shape. Stage II - Intralobular emphysema. Acinar filling with normal ventilation (A) or diffuse hypoventilation of the lobule (B). Preservation of lobular shape. Stage III - Lobular consolidations. Preservation of lobular shape. Stage IV - Patch distribution of lesions characterized by derangement of lobular structures. Changes in normal lobular shape. The identification of these lesions confirms HRCT as the most sensitive technique for the early visualization and localization of signs of CF bronchopneumonopathy. A broader experience coming from the systematic use of HRCT in chronic inflammatory lung diseases would increase our knowledge of pathogenetic processes and allow therapeutic perspectives to be improved. PMID- 1494678 TI - [Magnetic resonance imaging of the esophagus with lumen opacification using a specific contrast agent]. AB - A new contrast agent has been developed for the opacification of the esophageal lumen in Magnetic Resonance (MR) Imaging. The contrast agent consists of an emulsion of low-density and high-viscosity barium paste employed for the CT study of the esophagus (E.Z.E.M., Westbury, USA) and a small amount of Gadolinium-DTPA (Magnevist, Schering, Germany), diluted in 3 ml of saline solution. In vitro evaluation of the contrast solution showed high-signal intensity on T1-weighted SE sequences. The study was subsequently performed on 5 healthy volunteers and 30 subjects with clinical indication for MR Imaging of the chest. The complete opacification of the esophagus was obtained in 12 of the 16 patients (75%) who presented no pathological involvement of the esophagus. The esophageal lumen was completely opacified in 8 patients with esophageal carcinoma and in 1 case of esophageal leiomyoma. In the cases with esophageal carcinoma, lumen opacification allowed the evaluation of tumor growth (concentric or eccentric), a more detailed definition of tumor extent, with assessment of neoplastic wall thickening, and the evaluation of the possible infiltration of adjacent organs. Lumen opacification was obtained in 8 of 10 patients (80%) affected with other chest conditions secondarily involving the esophagus. In these cases, lumen opacification helped to localize the esophagus and to evaluate its involvement by adjacent tumors. PMID- 1494679 TI - [Oral contrast media in the study of the esophagus with magnetic resonance. Proposal of a new preparation]. AB - The major problem in MRI of the esophagus is the lack of a reliable oral contrast agent. To determine the value of Gd-DTPA as an oral contrast medium for the esophagus as a part of phase III clinical trial, 17 patients (10 esophageal neoplasms, 4 neoplasms of the pharyngo-laryngeal tract, 3 Zenker's diverticula) underwent MRI. The oral contrast medium is proposed in a new preparation: 5 cc of oral Gd-DTPA were emulsionated with 30 g of a low-density barium paste for esophageal CT (3% p/v). High signal intensity in the esophageal lumen was observed in all patients and in all sequences. In neoplastic lesions, the c.m. improved the definition of both the level of stenosis and the longitudinal extent of the lesion. In diverticula, the real and the false lumen could be demonstrated. In one patient the exam could not be completed. No adverse reactions were observed. PMID- 1494680 TI - [Ultrasonic diagnosis of gastroduodenal perforation]. AB - Ultrasonography (US) is routinely used as a diagnostic approach in the surgical acute abdomen, even though its major limitation is the demonstration of the hollow viscus. In the present paper, the results obtained with US in 12 cases of gastric or duodenal perforations are reported. The diagnosis, of gastroduodenal perforation was correctly made in 58% of cases by means of US; in 91.7% of cases, at least one US finding correlable with gastroduodenal perforation was observed. Even though US exhibits poorer diagnostic sensitivity than conventional radiology, it can be considered a valuable diagnostic tool in the early diagnosis of gastroduodenal perforation especially when radiographic findings are negative. PMID- 1494681 TI - [Role of echography in the differential diagnosis of accessory lobulations and small capsular traumatic fissures of the spleen]. AB - Emergency US in patients with abdominal trauma has become a routine diagnostic exam thanks to both its high reliability and its short acquisition time. US allows the overall evaluation of the patient, relative to both the localization of even very small fluid collections and the evaluation of traumatic changes in parenchymatous abdominal organs, especially the spleen which is often injured. Twelve patients were selected of all the cases submitted to emergency abdominal US between February 1989 and March 1992. All the cases with evident traumatic lesions of the spleen were excluded. In 10 cases US demonstrated interrupted splenic parenchyma, which was highlighted by intraperitoneal fluid collections; the interruption of splenic parenchyma is also evidenced by a thin hyperechoic capsular line with no changes in the echopattern of deep parenchyma. Surgery in 6 patients--4 of them as an emergency for hemoperitoneum and 2 operated subsequently--and US monitoring in the extant cases confirmed the diagnosis of simple accessory splenic lobulations. On the contrary, in 2 patients hospitalized in emergency, US showed no evident traumatic splenic alterations but only interruption of the hyperechoic capsular line with low hypoechogenicity in the splenic parenchyma below and a small fluid collection next to the lower splenic pole. Splenectomy confirmed a limited marginal tear of about 1.5 cm. The misdiagnosis of traumatic tears can be avoided if congenital splenic lobulation- evidenced by hemoperitoneum--is considered. US must also be employed to demonstrate minimal alterations in the hyperechoic capsular line of the spleen, in order to point out possible small tears and, if necessary, to suggest the need for clinical monitoring. PMID- 1494682 TI - [Role of echo-Doppler in the screening of renal artery stenosis in children with kidney transplants]. AB - Renal artery stenosis (RAS) in renal transplanted pediatric patients is a long term complication. The clinical suspicion must be considered when patients exhibit signs of impaired renal function or refractory hypertension, not associated with other complications of renal transplantation -i.e., acute or chronic rejection, glomerulonephritis, cyclosporine toxicity. The intermediate step between clinical suspicion and angiography is represented by Doppler US. The authors report their experience with Doppler US in the screening of RAS in a pediatric series of transplanted patients. The incidence of RAS in our series (54 transplanted kidneys, 46 of them included in the study) was 4.3%. A severe stenosis was demonstrated by both Doppler US and angiography in 2 patients, with 100% Doppler sensitivity. In both stenoses, Doppler US showed high systolic peaks (blood flow velocity > or = 2.5 m/s) and post-stenotic turbulence. Thanks to its high sensitivity, Doppler US is considered to be very useful in the screening of vascular complications in renal transplanted children. PMID- 1494683 TI - [Renal artery stenosis. Doppler color study before and after angioplasty]. AB - Doppler flowmetry can be successfully employed to assess arterial patency after percutaneous transluminal angioplasty (PTA). The aim of this study was to assess color Doppler sensitivity in detecting renal artery stenosis prior to percutaneous angioplasty (PTRA) and vessel patency after it. Eleven patients (7 males and 4 females) affected with renal artery stenosis, unilateral in 9 cases and bilaterally in 2, underwent color-Doppler evaluation 1 day before and 7 days after PTRA. The operator was unaware of dilatation results. A total of 13 stenoses were treated. The qualitative and quantitative parameters we employed were: a) broadening of the spectrum, b) peak systolic frequency > 4000 Hz, c) stenosis index > 50%. Before PTRA, mean systolic peak at the stenosis was 7978 (range 4050-12500 Hz), while stenosis index was 71.9% (range 48-89%). After PTRA complete recovery was observed in 5 cases, no improvement in 1 and incomplete recovery in 7. Doppler results were in agreement with those of angiography in 6/13 while partial agreement only was seen in 7/13. Our results, although obtained in a small and highly selected group of patients, would seem to support the value of color-Doppler for the follow-up of patients after PTRA. PMID- 1494684 TI - [Color-Doppler echography of the testis. Study technique and vascular anatomy]. AB - Color-Doppler sonography has recently made it possible to image scrotal vascularity non-invasively. This study was undertaken to determine the normal color-Doppler appearance and distribution of scrotal vessels and to define the technical principles of the examination. Color-Doppler imaging was effective in detecting both funicolar and testicular vessels. Among these, capsular (25/25), trans-testicular (10/25), centripetal and recurrent (25/25) arteries were easily identified. Waveforms analysis allowed to differentiate veins from arteries within testis and to distinguish (8/10) supratesticular (high impedance pattern with absent diastolic flow) from intratesticular arteries (low impedance pattern with high levels of diastolic flow). The optimal color depiction of scrotal vascularity needed the appropriate selection of several imaging parameters to increase detection of low-velocity, low-volume flows within the small testicular vessels. Such parameters included: PRF (ranging 1500 to 600 Hz), wall filters (ranging 25 to 50 Hz), color gain (maximized for optimal sensitivity while avoiding excessive color noise), color vs. echo priority (ranging 70 to 90%) and color persistence (adjusted to high values). In conclusion, color-Doppler imaging is capable of reliably showing the normal anatomy of testicular vessels. It could make a reliable substitute for scintigraphy and continuous wave Doppler in diagnosing scrotal conditions that alter blood flow. PMID- 1494685 TI - [Primary sarcoidosis of the breast: description of a case]. PMID- 1494686 TI - [Hodgkin's lymphoma localized in the lung parenchyma only. Considerations on a clinical case]. PMID- 1494687 TI - [Fibromuscular dysplasia of the internal carotid artery: percutaneous angioplasty]. PMID- 1494688 TI - [Radical therapy of pseudoaneurysm of the femoral artery with compression guided by color-Doppler]. PMID- 1494689 TI - [Imaging of adventitial cystic diseases of the popliteal artery. Description of 2 cases]. PMID- 1494690 TI - [Usefulness of ultrasonography in the diagnosis of fluid calculi of the urinary tract. Presentation of 4 cases]. PMID- 1494691 TI - [Extragonadal borderline serous cystadenoma of the peritoneum. Description of a case]. PMID- 1494692 TI - [Agenesis of the kidney, the seminal vesicle, and the homolateral vas deferens. Description of 2 cases]. PMID- 1494693 TI - [Bilateral post-traumatic dislocation of the testis. Description of a case]. PMID- 1494694 TI - [Experimental study of primary fixation of screw-ring acetabular components. Role of initial screw-cutting]. AB - Three types of screw-ring acetabular components were implanted to determine the characteristics of their holding power and to study the influence of screw cutting. The acetabular components were screwed into vinyl polychloride foam. Their resistance was measured. The optimal value of the locking screw couple and the value of the couple beyond the one at which the acetabular component loosened were determined. One of acetabular components was screwed in with and also without preliminary screw-cutting. Its resistance to wrenching was measured in both situations. The resistance curve at wrenching was characteristic of each screw-ring acetabular component. The resistance to wrenching was significantly higher (p < 0.01) for a given acetabular component if it was screwed into a largely open block of foam at its bottom. The screw-cutting allowed for a significantly higher resistance to wrenching (p > 0.05). It allowed for the screwing in with the least effort and for a better perception of the tightening. Knowledge of the comportment of screw-ring acetabular components once installed, usage of preliminary screw-cutting and recourse to a dynametric key are the means of improving the installation of screw-ring acetabular components. PMID- 1494695 TI - [Surgical treatment of spondylolisthesis with mild displacement by pedicular fixation and posterolateral fusion in adults]. AB - Thirty-two consecutive adults with low-grade spondylolisthesis treated by stabilisation with the AO Internal Fixator and posterolateral fusion have been retrospectively reviewed with a mean follow-up time of 4 years (range, 24 to 71 months). There were 17 grade I and 15 grade II spondylolisthesis. Eight patients had degenerative and 24 patients had isthmic spondylolisthesis. An unisegmental fusion was performed in 4 cases, a bisegmental fusion in 25 cases and 3 patients had a multisegmental fusion. There was one deep infection and one nerve root compromise (3 per 100). Satisfactory results were achieved in 84 per 100 of the patients. There was non-union. This study suggests that transpedicular fixation and posterolateral fusion significantly enhances the rate of solid union to an extent which outweighs the risk of neurological complications due to the screw insertion. Fusion in situ in patients with low-grade spondylolisthesis is recommended as well as nerve root revision for all adults with concomitant radioculopathy. However, this review does not specifically support the use of the AO-internal fixator, but rather that of transpedicular fixation in general. PMID- 1494696 TI - [Plexus nerve blocks for postoperative analgesia after orthopedic surgery of the lower limbs]. AB - In our institution, plexus nerves blocks have been performed in seventy patients after lower limb surgery. The technique is considered as simple and reliable. The administration of a 0.375 per cent bupivacaine epinephrine containing solution allows to obtain analgesia longer than 15 hours in 45 p. 100 of the patients, devoided of side effects. Lower limb plexus nerves blocks appear as an efficient technique for postoperative analgesia following orthopaedic surgery. PMID- 1494697 TI - [Atlanto-axial instability in children with trisomy 21: atlanto-axial (C1-C2) or occipito-axial (O-C2) arthrodesis?]. AB - A retrospective study involving seven cases of operated atlantoaxial (C1-C2) instability in patients with Down Syndrome prompted the authors to raise the following question: which kind of arthrodesis is to be performed for these patients? The possibility of an occipito-atlantal (O-C1) instability, is in fact relatively frequent in this condition, as the authors have observed themselves and in a literature survey; this is an argument for performing an occipito-axial (O-C2) arthrodesis. The difficulties met to reduce the C1-C2 luxation, the frequent pseudarthroses (3 cases in our series) and a tetraplegia following a re operation for non-union are as many other arguments to perform a O-C2 arthrodesis rather than a C1-C2 arthrodesis. PMID- 1494698 TI - [Rupture of the pectoralis major muscle: diagnosis and treatment. Apropos of 3 cases]. AB - Rupture of pectoralis major tendon is a rare lesion, often undiagnosed. We present 2 cases of complete rupture and one case of partial rupture. The 2 complete ruptures were treated surgically with, at follow up, a normally strong, painless shoulder and improved esthetics. The partial rupture remained nearly asymptomatic after conservative treatment. We recommend surgical repair of pectoralis major rupture, a lesion that remains symptomatic in the long term. Surgery should be done early, late repairs being technically more difficult and esthetic result less convincing. PMID- 1494699 TI - [Lipoma responsible for tarsal tunnel syndrome. Apropos of 2 cases]. AB - Two cases of tarsal tunnel syndrome caused by lipoma are reported. Both patients had ankle pain that radiated to the sole for years. On physical examination, localized swelling behind medial malleolus was found. Tinel's sign was provoked by gentle percussion on the posterior tibial nerve and its branches. Electrophysiological study showed fibrillation in foot intrinsic muscles or prolongation of motor and sensory latency of plantar nerves. Computed tomography of the tarsal tunnel demonstrated areas of low density indicating masses of high lipid content. Exploration of tarsal tunnel revealed compression of the medial plantar nerve by a lipoma. After excision of the lipoma, both patients had complete relief of ankle and foot pain. Computed tomography is helpful in delineating the nature and extent of lipoma within the tarsal tunnel. PMID- 1494700 TI - [Necessary hip disarticulation in extended echinococcosis of the femur]. AB - The authors have studied one case of pathological fracture of the femoral shaft related to hydatid disease. The diagnosis was based on the presence of whitish vesicles at the surgical procedure. Despite extensive, curettage and a number of other surgical procedures, infected drainage was persisting. The outcome was poor and a hip disarticulation had to be done. PMID- 1494701 TI - [Mathematical modelling of open-wedge tibial osteotomy and correction tables]. AB - This study analyzes mathematically the orientation of the superior tibial epiphysis in frontal and sagittal planes for knees with genu varum arthrosis. The assessment of the opening is determined mathematically for the osteotomies; this leads to the establishment of tables which can be used in practise during upper tibial osteotomies. PMID- 1494702 TI - [Lateral approach of the knee with tibial tubercle osteotomy for prosthetic surgery]. AB - The authors describe a lateral approach to the knee associated with a tibial tubercle osteotomy and a plasty using the fat pad to provide a complete closure of the wound. This lateral approach has been performed successfully in 98 cases, with only 3 skin necrosis. It offers a large exposure of the joint, facilitates placement of tibial component trial fit, and allows the self centering of the quadriceps patellar-tendon mechanism at the end of the intervention. The lateral approach disputable in case of genu varum is recommended in all cases of genu valgum or important deformities. PMID- 1494703 TI - [Changes in the heart rhythm and slow-release beta-2 agonist therapy (peroral) in asthmatic patients. A Holter study]. AB - Slow-release formulations of salbutamol, used in asthmatic patients, may have few effects on cardiac rhythm. This study was designed to compare incidence and type of cardiac arrhythmias in a group of ten patients with stable bronchial asthma before and after 6 weeks treatment with a slow-release formulation of salbutamol. After a baseline spirometric and electrocardiographic evaluation, patients received placebo for a two-weeks period. At the end of this period patients repeated spirometry and carried out a 24-hour-ambulatory-E-Holter-monitoring. Subsequently, patients received for 6 weeks a treatment with a slow-release formulation of oral salbutamol. At the end of this period patients repeated spirometry, a 24-hour-ambulatory-EG-Holter-monitoring and potassium serum levels were controlled. We concluded from our study that, in patients with moderate bronchial asthma the treatment with an oral formulation of slow-release salbutamol may carry out a significant and durable bronchodilator effect, without causing important cardiac arrhythmias. PMID- 1494704 TI - Salivary testosterone as an index of antiandrogen therapy in hirsutism. AB - The purpose of this study is to examine whether salivary testosterone (ST) in hirsute women treated with antiandrogen therapy can be considered a good parameter for the evaluation of clinical response. Twenty-three hirsute women, four with polycystic ovarian disease and 19 with idiopathic hirsutism were treated with cyproterone acetate and ethynyl-oestradiol with levonorgestrel in a reverse sequential regime for three months. Basal ST from hirsute women was 0.18 +/- 0.11 nmol/L (normal values 0.03-0.17) and a decrease to 0.11 +/- 0.06 was observed in the first month of treatment, to 0.1 +/- 0.059 after two months and to 0.11 +/- 0.06 after three months, all of them significantly different from basal values (p < 0.05). We found a relationship between ST decrease and the clinical response to antiandrogen therapy. On the basis of these results we suggest that ST values could be a good index for the follow-up of antiandrogen therapy in hirsute women. PMID- 1494705 TI - [Disability in rheumatoid arthritis: the predictive value of age and depression]. AB - Fifty rheumatoid patients were given the Health Assessment Questionnaire (HAQ) and the Arthritis Impact Measurement Scales (AIMS) in order to determine the contribution of clinical and demographic variables to the overall disability. Among the clinical variables, pain intensity and depression were carefully assessed along with the classic morning stiffness and the joint count and tenderness/Ritchie's index. Two main findings arose: age contributed on its own to the overall disability, while disease duration had no significant effects; joint count and tenderness (Ritchie's index) correlated in a highly significant manner with depression as derived from the AIMS subscale and the Zung Depression Inventory (ZDI). ZDI items were separated into a "somatic factor" and a "dysphoric factor", showing a clear-cut influence of the somatic factor on the disability score. Our results suggest that age of the patient, pain intensity and a depressive mood related to physical impairment are chief predictive factor of the overall disability in rheumatoid arthritis. PMID- 1494706 TI - [An in-vivo and in-vitro study of phagocyte migration in patients with AIDS]. AB - Polymorphonuclear leukocytes (PMN), are considered the first line of host defense. The PMN defects were related with an increase susceptibility to infections. We studied the neutrophil chemotactic function in 20 patients suffering from AIDS. The results of in vivo study demonstrated the decrease of chemotactic activity at 6 hour (p < 0.001) in the patients respect to control. The data of in vitro studies confirmed the granulocyte chemotactic defects, statistically significant, in the patients compared to the control subjects, when we used all chemotactic factors. These results showing the profound immune disturbances characteristic of the disease can favour infective susceptibility and complicate follow-up of AIDS. PMID- 1494707 TI - [Pulmonary embolism. A case report of right atrial thromboembolism treated by thrombolysis]. AB - This case report describes a 40-years-old man affected by fracture of leg and pulmonary embolism. Two-dimensional echocardiography showed a large right atrial migrant thromboembolus prolapsing into tricuspid valve during diastole. The patient was treated with rt-PA through right atrial venous catheter and underwent to serial echocardiographic examinations. The rt-PA determined the dissolution of the thrombo-embolus at the 2nd hour of infusion. It is concluded that early two dimensional echocardiography might be a very helpful technique to diagnose and follow-up therapy of pulmonary embolism. PMID- 1494708 TI - [Platelet hyperaggregation induced by an antiplatelet monoclonal antibody in a female patient with essential thrombocythemia of childhood]. AB - Essential thrombocythemia (ET) is a chronic myeloproliferative disease, rarely observed in pediatric age, characterized by a persistently increased platelet count. Abnormalities of platelet function observed in ET patients may be, at least in part, responsible for the thrombohemorrhagic complications. The authors report about a pediatric patient affected by ET, showing an abnormal platelet response following stimulation by anti-platelet monoclonal antibody. Such finding may be attributable to a structural abnormality of the platelet fibrinogen receptor or to post-receptor alterations. PMID- 1494709 TI - [The general practitioner and clinical records: a survey of the knowledge of users of a software package]. AB - The FATMA project--subproject 6, Line of Research 2--aims at implementing a new computerized information network for general practitioners using the same kind of software and homogeneously located throughout Italy. Thus, patients' case form data can be collected for public health purposes. After a study of literature in order to check whether other countries had implemented similar projects and what they consisted of, a survey based on a computerized questionnaire was carried out on a group of g.p.s. who had already received a software for the management of their clinical and professional activities from Janssen Informedica. This survey aimed at judging some aspects of users in order to select potential monitors of the information network who would test a new software. The analysis regards both g.p.s' social and professional data and the use of a computer package with reference to the quality and quantity of the clinical data they input. 2,010 questionnaires were filled in all their parts and mailed back to Informedica. It came out that g.p.s. believe more and more they can improve the organization and management of their work by using a software equipped with routines and easy access procedures so that clinical data, diagnostic reports and treatment can be collected, placed on files and updated. Thus, a new software should be developed. While meeting g.p.s' needs, it must overcome the limits of packages now available concerning the possibility of carrying out epidemiological studies. The software can become a tool to collect clinical data of patients, diseases and diagnostic procedures through standard protocols directly from g.p.s records. PMID- 1494710 TI - [Paget's disease: the prospects with ipriflavone]. AB - Paget's disease is a bone disorder characterized by high rates of bone remodelling. We have evaluated the efficacy of the new drug, ipriflavone, which has a double effect on the inhibition of bone reabsorption and on the activation of bone neodeposition. We studied 20 patients with active Paget's disease: 10 have been treated with 600 mg/die and 10 with 1200 mg/die of ipriflavone, for six months. In pharmacological wash-out, we have measured alkaline phosphatase, plasmatic BGP, the urinary hydroxyproline/creatinine ratio and the urinary calcium (Nordin Test). These valuations have been repeated after three and six months from the beginning of the administration of the drug. We have verified a propitious and speedy effect on pain, independent of dosage, and efficacy of treatment in function of bone turn-over parameter changes, by using no parametric statistical tests. In all subjects favourable effects have been found after three months treatment with 1200 mg/die. These have shown a greater efficacy than the lower dosage. After six months treatment we have not found significant differences as regards the efficacy of both dosages. These results may suggest to start therapy with higher initial doses and to carry-on with lower supporting doses. It's necessary to investigate further confirmation regarding the consolidation and perseverance of obtained favourable results, even after interruption of the treatment. PMID- 1494711 TI - [The diet therapy of rheumatic diseases]. AB - In the last decade the possible role of dietary therapy in the treatment of different rheumatic diseases has undergone serious reconsideration. Elimination diets may be useful in a subgroup of patients with rheumatoid arthritis, in whom food antigens probably play an important role in the onset and perpetuation of the inflammatory process. In mixed cryoglobulinemia a low-antigen-diet might reduce the amount of macromolecular food antigens which cross the mucosal barrier of the gut and cause either an immune response and/or compete with the immune complexes in the mononuclear phagocytic system. Supplementing the diet with essential fatty acids (omega-3 and/or omega-6) may inhibit the production of some of the mediators of inflammation, such as leukotriene-B4 and interleukin-1. However, currently employed doses often result in only modest or moderate clinical improvement. Controlled studies in a larger number of patients and with differentiated treatment protocols are needed to establish to what extent dietary therapy may improve the course of different rheumatic diseases, and to determine whether this therapy might be used in association with or even substitute for other well recognized treatments. PMID- 1494712 TI - [Isosporiasis and sarcocystosis. The current findings]. AB - A review on infections by Isospora belli and Sarcocystis spp. both in healthy and in AIDS patients is done on the basis of literature and personal data. In this view a special focus is made on isospora belli infection in AIDS because of its high recurrence after successful attack therapy. Consequently the most recent protocols for maintenance and attack therapy in these patients are reported. At the end, concerning ultrastructural pathology, the features of some Isospora belli developing stages are described by means of electron microscopy on duodenal biopsy specimens from a patient. PMID- 1494713 TI - [Vancomycin at the very lowest infusion rate and red man's syndrome]. PMID- 1494714 TI - The nutrition of elderly people. Report of the Working Group on the Nutrition of Elderly People of the Committee on Medical Aspects of Food Policy. PMID- 1494715 TI - Effects of cardiac oscillations on acinar gas mixing during pulmonary edema. AB - We used a previously reported technique (Mackenzie et al., J. Appl. Physiol. 68: 2013-2018, 1990) to measure the effects of severe pulmonary edema on acinar cardiogenic gas mixing in anesthetized dogs. We also tested how increases in lung volume affected gas mixing in healthy lungs and during pulmonary edema. Cardiogenic gas mixing was evaluated by measurement of the rate of washout of xenon133 injected into an occluded pulmonary artery during apnea. The rate constant of xenon133 washout was 0.40 min-1 (+/- 0.06 SE) in the healthy lung at functional residual capacity. It decreased (P < 0.05) to 0.08 min-1 (+/- 0.03) when lung volume was raised 500 ml. Pulmonary edema was induced by injection of oleic acid (0.06 mg.kg-1) into the right atrium over a 4-min period; clinical signs of severe pulmonary edema were present after 90 min. The rate constant for xenon133 washout (0.07 +/- 0.03 min-1) was less than in the healthy lung (P < 0.05), and was not changed after lung volume was increased (P > 0.05). We conclude that, in the presence of severe pulmonary edema: (1) acinar resistance is increased and/or magnitude of cardiogenic oscillations is decreased; and (2) salutary effects of increased lung volume are not due to enhancement of cardiogenic gas mixing. PMID- 1494716 TI - Collateral ventilation and the sloping alveolar plateaus of He and SF6: a model study. AB - In case of intralobular airway obstructions in dog lungs and in human lungs, ventilation of the regions distal to the obstructions appears to be surprisingly effective. In general, this is attributed to collateral ventilation which takes place between obstructed and adjacent, non-obstructed air spaces. In this paper we investigate the contribution of collateral ventilation to the distribution of gases in the lung and to the slopes of the alveolar plateaus (S) of the expirograms of He and SF6. To that end, we have simulated single-breath washout experiments with a mathematical lung model in which a fraction of the total acinar space was obstructed. The obstructed part was collaterally ventilated via the non-obstructed part by convection where both parts distended and retracted isotropically during the breathing maneuver. Collateral diffusion was assumed to be negligible during inspiration and expiration, but was taken into account for periods of post-inspiratory apnea (tA). With 20% of the total acinar space obstructed and tA = 0 sec, S(He) = 3.3%.L-1 and SSF6 = 4.7%.L-1. For both gases S increased with increasing degree of airway obstruction, and decreased with increasing tA and with increasing degree of collateral diffusion. For all simulated maneuvers the alveolar plateau was rectilinearly shaped. We conclude that in case of airway obstructions collateral ventilation may substantially contribute to the slope of the alveolar plateaus of the expirograms of He and SF6. PMID- 1494717 TI - Vagally mediated modification of inspiratory activity by changes in airway pressure. AB - The impact of varying the end-expiratory transpulmonary pressure (PE'tp) on phrenic (Phr) and parasternal intercostal (IC) activity early in inspiration was studied in 12 spontaneously breathing, anaesthetized cats. PE'tp was varied in a stepwise fashion by rapidly changing the tracheal pressure (Ptr) from ambient pressure to a pressure in the range between -1.2 and +1.2 kPa relative to ambient pressure, and vice versa. The amplitudes of integrated Phr and IC activity were determined in each breath at three particular points in time (t), corresponding to 0.1, 0.2 and 0.3 sec after the onset of Phr activity, respectively. For all three values of t, Phr and IC activity increased with a decrease in Ptr and decreased with an increase in Ptr. The relationships between Phr activity and PE'tp and between IC activity and PE'tp could be described satisfactorily by mono exponential functions. An increase in PE'tp of 0.1 kPa resulted in a decrease in Phr activity of 16%, 13% and 12% for the 3 aforementioned values of t, respectively. For IC activity the corresponding values were 42%, 42% and 36%, respectively. After bilateral vagotomy no changes in Phr activity in response to changes in Ptr were observed any more, whereas the changes in IC activity had decreased to about one tenth of the corresponding values obtained before vagotomy. Apparently, extra-vagal mechanisms contribute for a small part to the effect of changes in PE'tp on IC activity. Our results indicate that relatively small changes in PE'tp may have a large impact on central inspiratory output. PMID- 1494718 TI - Dual responses of carotid chemosensory afferents to dopamine in the newborn kitten. AB - The effects of dopamine and of dopamine D2 receptor blocker haloperidol on the activity of carotid chemoreceptors were studied in 24 anesthetized, paralyzed and artificially ventilated newborn kittens aged 0-17 days. Single or few fiber preparations of chemoreceptors were made from one carotid sinus nerve. The responses of the chemosensory afferents to intravenous injections of dopamine (5 50 micrograms.kg-1) were studied in kittens breathing air and 8% O2 in N2. The effects of haloperidol on the chemosensory activity in air or 100% O2 and on the chemosensory response to hypoxia were studied. Dopamine inhibited the chemosensory discharge in 25/44 studies in normoxia. Of the 9 studies performed in hypoxia, dopamine was excitatory in 5 or had no effect in 4 (P < 0.05 vs normoxia). Inhibition of the chemosensory discharge was observed in 24/37 studies performed in kittens aged more than 3 days and was predominantly excitatory in 6/7 studies in kittens aged 0-3 days (P < 0.01). One minute after haloperidol, the chemosensory discharge had increased significantly in all experiments. The biphasic pattern of chemosensory response to hypoxia (Marchal et al., Respir. Physiol. 87: 183-193, 1992) was not changed by haloperidol. The steady-state chemosensory activity was significantly increased after haloperidol, respectively from 3.9 +/- 0.7 impulses.sec-1 to 9.8 +/- 1.2 impulses.sec-1 in air, and from 13.1 +/- 1.4 impulses.sec-1 to 17.8 +/- 2.4 impulses.sec-1 in hypoxia (mean +/- SEM, P < 0.03). It is concluded that the dopaminergic mechanisms are active in the carotid body of the kitten, and the observed responses to dopamine and haloperidol are qualitatively similar to those reported in the adult cat. PMID- 1494719 TI - Response of roosters to resistive loads at constant chemical drive to breathe. AB - This study investigated the role of mechanoreceptors in the respiratory responses to resistive loading in roosters. Adult roosters were unidirectionally ventilated (maintaining a constant chemical drive to breathe). Electrical circuits assessed the respiratory muscle pressure (Pmus) and controlled the relationship between Pmus and the respiratory volume changes. Respiratory volume changes similar to those achieved by flow-resistive unloading or loading were produced by the circuits, imposing a 'virtual' resistance (Rv). When Rv was doubled (decreased rate of volume change, n = 6), tidal volume (VT, measured by whole body plethysmography) decreased significantly (28%), while thoracic volume (VRIP, measured by respiratory inductance plethysmography) did not change. When RV was quadrupled (n = 4) VT and VRIP decreased significantly (53% and 24%, respectively). Changing RV to one half the normal value (n = 5) did not affect these parameters. Inspiratory time and Pmus were not significantly altered at any RV. It is concluded that, at constant chemical drive, mechanoreceptors play a minimal role in maintaining tidal volume during impeded breathing in roosters. Comparative differences which may explain these results are discussed. PMID- 1494720 TI - Effects of exercise modality on patterns of ventilation and respiratory timing. AB - Ventilatory patterns and respiratory timing were measured in 14 subjects during cycling (CYC) and treadmill exercise (TM) at similar leg frequencies (fLEG) to determine if mode of exercise affects patterns of ventilation and respiratory timing. Measurements of breathing frequency (fR), tidal volume (VT), expired ventilation (VE), and inspiratory (TI) and expiratory (TE) time were obtained at fLEG of 50, 70, and 90 rev.min-1 (rpm) for CYC and at similar incremental fLEG (strides.min-1; spm) during TM achieved by increasing belt speed at 0% grade. CYC exercise intensity was approximately 50% VO2,max at all fLEG, whereas VO2 increased progressively with TM. fR increased significantly (P < 0.001) with increasing fLEG of TM (20.5 +/- 4.6, 25.4 +/- 5.8, and 36.3 +/- 7.6 breaths.min 1; mean +/- SD), but during CYC fR changed significantly (P < 0.05) only between fLEG of 70 and 90 rpm (25.0 +/- 5.9 vs 28.5 +/- 6.9 breaths.min-1). Both average breath TI and TE obtained by grouping into incremental ranges of fR decreased significantly (P < 0.05) with increasing fR up to 36 breaths.min-1 and the relationships of TI and TE to fR, TI to TE, and central inspiratory drive (VT/TI) to VE were the same for CYC and TM. Group average fR and fLEG were synchronized during TM, but individual subjects did not exhibit a high degree of entrainment. This study shows respiratory timing patterns to be independent of mode of exercise over the range of fR observed when describing patterns by grouping into incremental ranges of fR. PMID- 1494721 TI - Fatigue-induced changes in diaphragmatic afferents and cortical activity in the cat. AB - The rationale for the present study was to test the hypothesis that changes in phrenic sensory activity during diaphragmatic fatigue may modify the transmission of phrenic afferent action potentials to the cortex and also the spontaneous EEG activity. This was performed in anesthetized cats. Diaphragmatic fatigue was produced by intermittent direct muscle stimulation for a 30 min period. Diaphragmatic metaboreceptors (tonically active afferents) and mechanoreceptors (phasic phrenic activity) were identified by their activation by intraarterial lactic acid injection or their discharge in phase with diaphragmatic contraction, respectively. Cortical phrenic evoked potentials (CPEPs) and spontaneous EEG activity were recorded from the left sensorimotor area. Diaphragmatic failure was shown from the 10th minute of stimulation. Then, the activity of tonic phrenic afferents increased markedly whereas, in parallel, the phasic discharge of mechanoreceptors decreased progressively. This was associated with progressive lengthening in onset and peak latencies of CPEPs. The main EEG changes (visual and fast Fourier transform analysis) were characterized by a transient increased energy in the delta frequency band during the first minutes of the fatigue run, followed by decreased energy in the theta frequency band after 11-25 min of stimulation. Denervation of the diaphragm suppressed the EEG changes during the fatigue run. The present observations suggest that the cortical integration of sensory information from the diaphragm may be altered during fatigue. PMID- 1494722 TI - Tissue PO2 and growth rate in early chick embryos. AB - We determined dry mass, frequency distribution of tissue PO2 and microvascular density of head and trunk of early chick embryos between day 4 and day 6 of incubation. During this period the percentage of the dry mass of the head on total dry mass increased from 31% to 48% indicating that the head grows faster than the trunk. Tissue PO2 values ranged between zero and arterial PO2. About half of the numbers were less than 5 Torr. Mean tissue PO2 was significantly higher in the head than in the trunk. This was paralleled by a significantly higher microvascular density in the head. The high frequency of low tissue PO2 values found at each day at all measuring sites suggests that the embryonic tissue of both head and trunk extracts as much oxygen from the capillary blood as possible. Consequently, growth rate strongly depends on oxygen availability. Since the arterial PO2 is the same in the head and in the trunk (Meuer and Baumann, 1988), the diversity of tissue PO2 and growth rate found in this study is probably caused by differences in the structure of the microvascular bed resulting in variations of tissue blood perfusion, capillary transit time and diffusion distance. PMID- 1494723 TI - Responsiveness to histamine in human sensitized airway smooth muscle. AB - Passive sensitization of human isolated airway smooth muscle increases contractile responses to histamine. We looked to see whether this increase was due to an alteration in the relative role of histamine H1 and H2 receptors. Human bronchial spiral strips obtained at thoracotomy were passively sensitized by incubation in serum from atopic asthmatic patients to Dermatophagoides pteronyssinus and control strips were incubated in serum from healthy non allergic non-atopic subjects. We also studied spiral strips dissected from two spontaneously sensitized human lung specimens. Cumulative concentration-response curves (CCRC) to Ca2+ (10(-5) -3 x 10(-2) M) were constructed either in the presence of 10(-5) M histamine alone or in that of the combination histamine and the H2 antagonist cimetidine (10(-5) M). Unlike in the absence of histamine, Ca2+ CCRC in the presence of histamine alone were significantly shifted to the left in the passively sensitized tissues (mean EC50: 5.7 x 10(-4) M) compared to control ones (mean EC50: 9.3 x 10(-4) M, n = 6, P < 0.05). Addition of cimetidine to histamine did not alter the Ca2+ CCRC either in the control or in passively or spontaneously sensitized airway smooth muscle. These results suggest that (i) passive sensitization increases contractile response to Ca2+ of human bronchial smooth muscle in the presence of histamine; (ii) this increase is not due to a difference in the H1- vs H2-mediated response; and (iii) H2-mediated effects do not play a significant role in spontaneously sensitized human lung as both in the non-sensitized and passively sensitized lung. PMID- 1494724 TI - [Neurological, dermatological and biological manifestations of porphyria variegata. A study of 3 families of Italian origin in Marseilles area]. AB - Three kindreds of Italian descent with variegate porphyria are described. These families are now living in Marseilles and surrounding regions. The first kindred originating from Torre del Greco, near Naples, is living in Arles. This family includes two propositi who experienced an acute attack with visceral and neuropsychiatric manifestations. The family's survey was carried out by measuring protoporphyrogen oxidase (PO) activity in lymphocytes (normal values = 4.8 +/- 1.2). Seven of the 20 subjects tested, beside the two propositi, were found to be asymptomatic carriers (PO < 3.6). The first index patient, a 41-year old man, was first observed at the age of 31 with acute and psychiatric manifestations after rifampicin treatment; the cutaneous symptoms appeared one year later. For the second propositus, a woman presenting with abdominal and psychiatric manifestations, the age of onset was 38 years; the acute attack had no recognizable cause; she had mild skin lesions and initially was incorrectly diagnosed as intermittent acute porphyria; the diagnosis of variegate porphyria was only established at the age of 50 years. The second family, originating from la Spezia and Vernazza, is living in Marseilles. The propositus, a 50-year old man, developed cutaneous symptoms at the age of 30. A diagnosis of porphyria cutanea tarda was initially made. The first and unique acute attack with abdominal and neurological manifestations recurred at the age of 41. The diagnosis of variegate porphyria was established on laboratory data. Physical stress was probably the cause of the acute attack. Beside the propositus, out of 9 subjects tested 6 were asymptomatic carriers.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1494725 TI - [Cerebrotendinous xanthomatosis. 2 cases with magnetic resonance imaging]. AB - A 40-year-old woman presented with bilateral juvenile cataract, tendinous xanthomas, intellectual deterioration, spastic tetraparesis, proprioceptive deficit and parkinsonian syndrome. A younger sister's clinical picture differed by the absence of xanthomas and the presence of a cerebellar syndrome. The diagnosis of cerebrotendinous xanthomatosis was confirmed by a high concentration of plasma cholestanol and by urinary chromatography. Magnetic resonance imaging displayed some abnormalities in the hemispheric and cerebellar white matter. Under chenodesoxycholic therapy the biological abnormalities decreased while the clinical disturbances were unchanged. PMID- 1494726 TI - [Rademaker and Garcin syndrome associated with pallidal calcifications]. AB - We report gait abnormalities with exaggerated support against gravity in a 76 year-old woman. This exaggeration, and its demonstration by ankle dorsiflexion in supine position, was first described by Rademaker and Garcin (1933) as probably resulting from cerebellar and brainstem lesions. In the present case, quantitative analysis of locomotion showed a strong reduction in both stride duration and stride length. There was an increased variability between two consecutive locomotor cycles and a large increase in both stance duration and relative double-support duration. Electromyography clearly showed leg hypertension following ankle dorsiflexion, contrasting with normal leg mobility in the supine patient. This suggested that reflexive antigravity support abnormalities could explain this pattern of locomotor disabilities, differentiating them from other kinds of "marche a petits pas". The present case was associated with bilateral pallidal calcifications, suggesting an involvement of the basal ganglia in support reaction against gravity and in control of adequate postural muscle tone necessary for locomotion. PMID- 1494727 TI - [Cerebrovascular disorders in young adults in Saudi Arabia. A study of 136 cases]. AB - We report our experience of stroke in 136 young adults aged from 18 to 45 years seen in the Eastern Province of Saudi Arabia over a 10-year period. They constituted 25% of all our stroke cases. Thirty-eight percent were Saudi nationals and 62% expatriates. Males largely outnumbered females. The frequency of cerebral infarction (54%) was not very different from that of intracranial hemorrhage (45%). Atherosclerosis and embolism of cardiac origin were the major causes of infarction. The main causes of intracranial bleeding were arterial aneurysms, arteriovenous malformations and hypertension. However, the causes of 29% of ischemic strokes and 44% of hemorrhagic ones remained undetermined. Interethnic comparison of the causes showed that hemorrhages were significantly more frequent in Far East immigrants. Sixty five percent of cerebral infarctions in Asiatic patients remained of undetermined origin. The local variant of sickle cell gene did not seem to play a major role in the pathogenesis of stroke in the Saudi young adult. These data are commented and compared with similar reported data. The influence of the demographic structures of the Saudi population and immigrants communities is analyzed. PMID- 1494728 TI - [Carotid artery obstruction caused by vagal paraganglioma]. AB - A 72 year-old-man presented with right hemiparesis and global aphasia related to a large infarct in the left middle cerebral artery territory. A left carotid angiography revealed internal carotid artery occlusion and vascular blush just below the base of the skull. The blush was supplied by branches from the external carotid artery. Cervical CT-scan showed a large tumor centered by the left internal carotid artery. At cervical surgery, the internal carotid artery was compressed and infiltrated by the tumoral process: a benign paraganglioma. The site below the base of the skull and the connection between tumor and vagal nerve suggested a vagal paraganglioma. To our knowledge, this is the first case of cerebral infarction and internal carotid artery occlusion revealing a vagal paraganglioma. PMID- 1494729 TI - [Facio-linguo-masticatory diplegia and epilepsy. Cortical dysplasia]. AB - Neuronal migration anomalies are caused by insults occurring during the third to fifth gestational months when neuroblasts migrate from the germinal zone to the cortical plate. They lead to several cerebral malformations such as macrogyria, identified nowadays by MRI. We describe a case of bilateral parieto-rolandic macrogyria responsible for a bi-opercular syndrome resulting in a facio-linguo masticatory diplegia associated with mental retardation and severe epilepsy. PMID- 1494730 TI - [Left prerolandic infarction with initial epilepsy. Development of chronic hallucination psychosis]. AB - A 34-year-old woman had three tonico-clonic seizures and aphasia revealing a left prerolandic infarct. Three weeks later, she began to develop psychiatric symptoms leading to the diagnosis of chronic hallucination psychosis. These symptoms were probably related to epilepsy and their cause was compatible with the diagnosis of interictal psychosis. It has been suggested that kindling of the mesolimbic system could account for psychosis in epilepsy. In our case, however, the sort time interval between the onset of epilepsy and the appearance of psychosis is not in favour of this mechanism. PMID- 1494731 TI - [Systematized cavernous angiomatosis with multiple cerebral and cutaneous localizations]. AB - A 45 year-old woman with no history of familial disease presented with multiple cutaneous and cerebral cavernous angiomas. The diagnosis rested on biopsy for cutaneous angiomas and on MRI for cerebral angiomas. The clinical manifestations of cerebral angiomas were headaches and a cerebellar syndrome, the latter most probably due to progressive growth of cerebellar angiomas. Systematized cavernous angiomatosis is characterized by multiple angiomas of the brain and other viscera and is considered to be a phacomatosis. PMID- 1494732 TI - [Unilateral scapulohumeral amyotrophy. Contribution of imaging]. AB - A case of right scapulohumeral muscular atrophy stable after a 6 month progressive course is reported. Cervical metrizamide CT and MRI showed a flattened right cervical spinal cord regarded as a segmental atrophy. The case could belong to the Kaeser type of sporadic chronic spinal amyotrophy, or perhaps corresponds to a benign focal amyotrophy. PMID- 1494733 TI - [Acute renal failure complicating carbamazepine hypersensitivity]. AB - A case of acute renal failure occurring during treatment with carbamazepine is reported. The clinical signs and biological abnormalities strongly supported the diagnosis of acute interstitial nephritis of immunoallergic origin. The outcome was favourable after drug withdrawal. We review the cases of carbamazepine induced acute renal failure. PMID- 1494734 TI - [Prognosis of transient ischemic accidents disclosing infarction]. AB - In a prospective study, thirty six out of 175 consecutive patients (21%) with transient ischemic attack (TIA), had cerebral infarction on CT-scan. This group of patients differed from the group without cerebral infarction by a higher age, a longer duration of neurological deficit, a greater frequency of neurological history, vertebro-basilar TIAs, cephalagia and, cardiac arrhythmia, and by a higher 2-year mortality rate. Due to their difference in etiological factors and prognosis, TIAs with cerebral infarction on CT-scan should be differentiated from those without cerebral infarction. PMID- 1494735 TI - [A case at Salpetriere hospital November 1990. Parkinson syndrome with poor response to dopa therapy in a 64 year-old man]. PMID- 1494736 TI - [Investigation of phosphorus calcium metabolism after oral phosphorus supplementation]. AB - Effects of oral administration of phosphorus on phosphorus and calcium parameters and on bone metabolism hormones were investigated in two studies: in the first, 12 young female adults and 8 females over 50 years of age took a single oral load dose of 780 mg elemental phosphorus, whereas in the second study assays were performed 5 and 15 days after initiation of twice-daily phosphorus supplements in 19 young adults, 14 subjects above 50 years of age who were free of osteoporosis, and 12 patients with osteoporosis also over 50 years of age. The phosphorus load was associated with an increase in intact parathyroid hormone levels (iPTH 1-84), which was more marked in subjects above 50 years of age than in younger adults. On the 15th day of phosphorus supplementation, there was no significant increase in baseline iPTH and no change in baseline dihydroxyvitamin D or osteocalcin levels; during the Nordin tests, the fractional calcium excretion index (CaU/CrU) and the fractional hydroxyproline excretion index (OH Pro/CrU) remained unchanged. In contrast, the phosphorus load was followed by a decrease in the maximum phosphorus reabsorption threshold (TMP/DFG), which was more marked on the 5th day than on the 15th day; a slight fall in serum phosphorus levels was also seen on the 15th day. These findings suggest that phosphorus supplementation should be intermittent rather than continuous. Analysis of subjects aged 50 to 69 years failed to disclose any significant differences between patients with and without osteoporosis. PMID- 1494737 TI - Correlation between knee roentgenogram changes and clinical symptoms in osteoarthritis. AB - The main purpose of this study was to analyze the relationship between clinical symptoms and roentgenographic changes in patients with incipient osteoarthritis of the knees (OA). One hundred and sixty-two patients (126 women, 36 men, mean age 59 years) with established osteoarthritis of the knee were examined. Patients performed subjective self-assessment using Lequesne's questionnaire (index of severity for OA of the knee) and had frontal and lateral roentgenograms of both knees. Validity of the indices as reflections of individual symptoms was documented. A statistically significant correlation was found between clinical and patient indices (r = 0.327, p < 0.0001) as well as a very weak correlation between the clinical and roentgenogram indices (r = 0.196, p = 0.286). However, there was no correlation between the patient index and roentgenogram index (r = 0.065, p = 0.47). For the assessment of severity and progression of the disease, items reflecting acute irritation (swelling, effusion, increased joint temperature, pain during passive motion) were more reliable than items reflecting chronicity (muscular atrophy, decreased range of motion, crepitus). This study confirmed that Lequesne's questionnaire is a suitable tool for assessing subjective symptoms as well as for generating a condensed measure of disease severity. In addition, sclerosis, narrowing and osteophytes were proved to be important features characterizing the OA process. PMID- 1494738 TI - [Severe hypocalcemia complicating outbreaks of renal failure in 2 uremic patients]. AB - Hypocalcemia has many causes of which several often occur in combination in intensive care unit patients. Two cases (a 78-year-old male and a 63-year-old female) of severe hypocalcemia (corrected serum calcium 1.2 mmol/l in both cases) in patients hospitalized for acute decompensation of chronic renal failure are reported herein. Both subjects had a history of chronic hypocalcemia due to vitamin-calcium deficiencies and chronic renal failure. The lack of adverse clinical consequences of the low serum calcium levels can be explained by the fact that both patients also had severe metabolic acidosis, a disorder which increased the ionized fraction of total serum calcium. Serum calcium returned to normal slowly and gradually despite parenteral administration of large amounts of calcium and vitamin D or vitamin D derivatives. PMID- 1494739 TI - [Sciatic radiculalgia with muscular hypertrophy]. AB - A 52-year-old male developed hypertrophy of the right calf after several bouts of right lumbar pain with sciatica. Electromyography disclosed evidence of demyelination in the territories of the right S1 and S2 roots. Microscopic studies showed both atrophic muscle fibers scattered among fibers of normal caliber and a large number of hypertrophic fibers. Post-sciatica hypertrophy of the calf is a true muscle hypertrophy with muscle weakness. Electromyography may show unusual tracings with repeated complex bursts or continuous activity of motor units. Muscle enzyme levels may be elevated. The size of hypertrophied fibers varies across cases. The cause of the muscle fiber hypertrophy may be either stretching due to the action of antagonists or unusual electrical activity. PMID- 1494740 TI - [Rheumatoid aortic insufficiencies: severity of the prognosis]. AB - Rheumatoid aortic incompetence is infrequent, with only 43 cases published in the literature. Seven additional patients (5 females and 2 males) with rheumatoid arthritis (RA) and aortic incompetence are reported herein. All seven patients had seropositive RA with severe joint disease and extraarticular manifestations (nodules, cutaneous vasculitis, multiple neuritis). Development of aortic incompetence was unrelated to age or duration of RA. The aortic disease was diagnosed upon the development of sudden heart failure (pulmonary edema) in three patients and during a routine evaluation in the other four. The course was extremely severe with a fatal outcome in five patients, of whom the youngest was only 24. Only one patient had valve replacement surgery; however, this patient died 8 days after the procedure. Mean survival in the seven patients was 20 months (range 7-56) from diagnosis and 11 months (range 1-28) from the first manifestation of heart failure. Histologic studies done in the only patient who had surgery demonstrated a rheumatoid granuloma in the pericardium and lymphocytic infiltrates in the pericardium and aortic valve. PMID- 1494741 TI - [Chronic sarcoidosis-polyarthritis with infantile onset. Persistent synovial granulomas under corticotherapy]. AB - The case of a patient who developed sarcoidosis with chronic joint symptoms at the age of four and still has active disease twenty years later despite three years of corticosteroid therapy is reported. During the course of the disease, specific histologic features of sarcoidosis were evidenced twice in synovial specimens, twice in skin biopsy specimens, and once in bronchial tissue. Deformations and joint lesions developed in the hands and feet. The combination of arthritis, skin lesions, and uveitis occurs both in juvenile-onset sarcoidosis and in chronic juvenile joint diseases, raising significant diagnostic problems which can be solved by histologic studies of synovial or skin biopsy specimens. PMID- 1494742 TI - [Bone condensation and enterocolitis: SAPHO syndrome. Apropos of a case]. AB - A new case of SAPHO syndrome with lesions confined to the spine and concomitant enterocolitis reported. Only eight cases of this rare combination have been published to date. Bone involvement consisted in sclerosis of vertebral bodies of T10 and T11, raggedness of the vertebral plateaux from T7 to T10, and thick syndesmophytes bridging the vertebrae from T7 to T11. Erythrocyte sedimentation rate was 108 in one hour. Systemic corticosteroids were given after failure of nonsteroidal antiinflammatory agents and recurrence of iritis. Pain resolved promptly and the erythrocyte sedimentation rate returned to normal. This case is unusual both because this combination of diseases is rare and because virtually complete resolution of vertebral sclerosis was noted after one year of corticosteroid therapy. Possible relationships between the SAPHO syndrome and the group of spondylarthropathies are suggested and discussed. PMID- 1494743 TI - [Effects of methotrexate on leukotriene and derivated lipoxygenase synthesis in polynuclear neutrophils in rheumatoid polyarthritis]. AB - Methotrexate (MTX) has been proved to be effective in rheumatoid arthritis (RA). The mechanism of action of MTX in this disease remains unelucidated but may involve inhibition of the enzyme 5-lipoxygenase. Arachidonic acid metabolites were studied in eight patients with active RA immediately prior to and 24 hours after the first intramuscular injection of 10 mg MTX. None of the patients were taking corticosteroids. Nonsteroidal antiinflammatory drugs were withdrawn four days before the study. Reverse phase high-performance liquid chromatography was used to quantitate metabolites produced by 5-lipoxygenase (5-LO) and 12-LO in plasma (full spectrum of blood cells) and purified neutrophils (PN) after stimulation with calcium ionophore A 21387 (50 microM for 30 minutes and 5 microM for 5 minutes, respectively). LTB4 production by PNs was significantly decreased (-32%, p < 0.01) 24 hours after MTX administration. A moderate (-17%), nonsignificant (NS) fall in LTB4 omega-oxidation products (wP) was seen. Production of 5-HETE was also slightly decreased (-15%, NS). Findings in plasma were comparable, with a significant decrease in total LTB4 (-29.8%, p < 0.01) and moderate falls in wP (-18.8%, NS) and in 5-HETE production (-17%, NS). Production of 12-HETE was unchanged. These findings suggest that MTX in a single dose is responsible for a decrease in the synthesis of LTB4 and 5-LO products in neutrophils and other blood cells in RA patients but does not affect 12-LO activity. PMID- 1494744 TI - [Cervical pain revealing Hodgkin's disease. Apropos of a case]. PMID- 1494745 TI - Swedish Association of Urology. Proceedings of the Annual Meetings. Stockholm, November 30-December 1, 1989 and December 6-7, 1990. Abstracts. PMID- 1494746 TI - Swedish Association of Urology. Proceedings of the Annual Meeting. Stockholm, November 28-29, 1991. Abstracts. PMID- 1494747 TI - [Zinc. Elements of the aquatic environment III. Data on water, sediment, organisms and ecotoxicology]. PMID- 1494748 TI - [The value of epidemiologic studies of ski injuries]. AB - The Garmisch-Partenkirchen experience--15,513 skiing injuries between 1972 and 1990--was compared to the results of an inquiry into the skiing injuries among 565 persons of the medical profession, that were active skiers over an average of 18 years. The parameter injuries per 1000 skiing days was calculated from the outpatient clinic data as well as from all skiing injuries that had happened in the interview group and those that required surgical treatment. The mean value of 2.7 injuries/1000 skiing days--corrected for the number of patients--from the literature and the clinical data with 2.1 is comparable to the 1.8 injuries/1000 skiing days (injuries that required surgical treatment) but stands sharply against the 4.2 arising from the total number of injuries in the inquiry group.- Thus, every epidemiological study clearly underestimates the actual rate of skiing injuries. This fact may be defined as the "bypass-effect". The comparison between clinical setting and inquiry allowed for a quantification: Depending on the type of injury and the study design, a true prevalence of skiing injuries that is between 10% and 200% higher than the published data has to be expected.- Descriptive, not controlled epidemiologic studies on skiing injuries are justified and give valid trends on which therapeutic and prophylactic measures can be based--but exclusively under the following prerequisite conditions: 1. a standardized study protocol; 2. an observation. PMID- 1494749 TI - [The spine--a problem area in high performance artistic gymnastics. A retrospective analysis of 24 former artistic gymnasts of the German A team]. AB - 24 former female artistic gymnasts of the German national team were examined for spinal deformities after the end of their athletic career. In 3 cases we found osseous lesions of the spine without neurological complications. However, emphasis was on spinal changes due to stress. During their athletic career 15 gymnasts complained of low back pain which persisted in 7 of them after finishing their athletic activities. The lumbar radiographs revealed bilateral spondylolysis at L5 in 6, unilateral spondylolysis in 1, spondylolisthesis at L5/S1 in 3, degenerative changes of the intervertebral joints in 5, retrolisthesis at L5/S1 in 2, and scoliosis in 6 cases. PMID- 1494750 TI - [Structure of the palmar plate of the proximal interphalangeal joint with reference to the typical injury pattern in hyperextension trauma of the finger. A morphometric, densitometry and histologic study]. AB - The palmar plates of the PIP of the fingers are examined in 43 hands. Apart from macroscopic morphometric studies special attention is paid to the density of bone in the areas of insertion, measured with the help of a computerized image analysing system. Especially the distal area of insertion in the basis of the medial phalanx shows a low density of bone. The consequent low adaptation to stress explains clinical findings, describing most frequent osseous ruptures of the palmar plates in case of hyperextension injuries to the fingers. The fibrous structure of the palmar plate is studied in histological sections. A palmar layer of transversally running collagenous fibres, as well as a medial layer of diagonally and a dorsal layer of longitudinally running fibres can be differentiated. The distal area of the palmar plate mostly consists of transversal, the proximal area of longitudinal collagenous fibres. Therefore a hyperextension stress, hitting the fibres in a right angle distally, cannot be neutralized sufficiently. This result is closely linked to clinical observations describing mostly distal ruptures of the palmar plate in spite of its proximal region being of weaker structure. PMID- 1494751 TI - [Diagnosis and treatment of ligament injury of the thumb base joint. Results within the scope of follow-up]. AB - Distortions and ruptures of the ulnar collateral ligament of the metacarpophalangeal joint of the thumb represent 6% of hand injuries in alpine skiing and 8% in ski-skating. 155 patients who had been treated for ligamentous rupture (88), for osseous rupture with dislocation of the fragment (42) and for osseous rupture without any dislocation (25) wer reviewed: in 106 patients with conservative treatment 64 had stable joints and 42 showed a ligamentous instability. After surgical treatment in 49 patients 44 had ligamentous stability; 5 joints (10%) showed a radial instability. Summarizing the results we found instability after conservative treatment in 40%, but only in 10% of surgically treated patients. Recommendations for the treatment of this frequent hand injury are given. PMID- 1494752 TI - [Importance of the subchondral space for development of chondromalacia patellae- morphologic study of joint cartilage of the rabbit patella after experimental ischemia]. AB - The aetiology of chondromalacia patellae and especially the importance of the subchondral space have not been clarified to date. However, clinical findings yielded pointers to a connection between degenerative changes of the articular cartilage and an influence exercised by the subchondral space. In our experiments we performed an operative ischaemia of the patella with interruption of the vascular inflow and outflow on 40 adult rabbits for exactly defined times (2 weeks, 6 weeks, 3 months, 6 months). The examinations were carried out using the plastination method, histology, transmission electron microscopy, and scanning electron microscopy. Marked changes can be seen from the third month onwards: disappearance of the tidemark, degeneration of the cartilaginous cells (formation of clusters) and onset of trachomatous keratitis. These degenerative changes progress further in the animals of 6 months of age. The results indicate that metaplasia of the tidemark plays a significant part in the pathogenesis of degenerative changes of the cartilage. Hence, chondromalacia patellae can be caused by subchondral vascularisation disorders.--This is, therefore, a new concept for the aetiopathogenesis of chondromalacia patellae, a disease pattern that is of great importance in sports orthopaedics. PMID- 1494753 TI - [Securing the syndesmosis suture by syndesmosis hook in extreme stress caused by long-distance running. A case report]. AB - The elastic fixation of the distal tibiofibulary syndesmosis by means of Engelbrecht's hook allows weight bearing and free dorsal flexion. The example of an 40-year-old long distance runner (and surgeon) shows that this system can endure extreme stress: during the 9 months until the metal was removed, he took part in 14 contests with excellent results. He ran at least 100 km per week, together more than 3700 and classical marathons, 100 km runs and mountain marathons. When the metal was removed there was no sign of metallotic changes of the tissue at the interface between hook and plate. PMID- 1494754 TI - [What is the proper position for the back dressing?]. PMID- 1494755 TI - [Medical report and recommendations]. PMID- 1494756 TI - [Trends in sport-medical care (also) in large athletic events. Team management or medical magic]. PMID- 1494757 TI - [Barcelona from the Swiss viewpoint]. PMID- 1494758 TI - [Team physician of the national basketball team at the 1992 Olympics]. PMID- 1494759 TI - [The 1992 Olympics]. PMID- 1494760 TI - Detection and quantification of pulmonary emphysema by computed tomography: a window of opportunity. PMID- 1494761 TI - Diagnosis of Pneumocystis carinii pneumonia in HIV antibody positive patients by simple outpatient assessments. AB - BACKGROUND: As increasing numbers of patients with immunosuppression induced by the human immunodeficiency virus (HIV) present with respiratory symptoms it is important to differentiate Pneumocystis carinii pneumonia from other chest diseases rapidly and start treatment early. The management of pneumocystis pneumonia could be improved if clinicians could diagnose this condition confidently on the basis of simple clinical assessments. METHODS: Three hundred and eighteen patients with evidence of immunosuppression due to HIV infection and suspected pneumocystis pneumonia were investigated. A clinical history was taken and arterial blood gas analysis, chest radiography, oximetry during exercise, and sputum induction or bronchoscopy (or both) were performed. RESULTS: Pneumocystis pneumonia was confirmed microscopically from induced sputum or bronchoalveolar lavage fluid in 154 patients; 118 had other chest disease. The remaining 46 patients had no definitive diagnosis. The best single independent predictors of a diagnosis of pneumocystis pneumonia were exercise induced oxygen desaturation and obvious interstitial infiltrates on the chest radiograph (odds ratios of 4.88 and 5.44 respectively). The symptom triad of exertional dyspnoea, cough, and fevers; the absence of pneumocystis pneumonia prophylaxis; and resting arterial hypoxaemia were less predictive (odds ratio 2.07, 3.72, and 0.69). An algorithm was developed that gave a positive predictive value for confirmed pneumocystis pneumonia of 95% and also identified those patients with a very small chance of having pneumocystis pneumonia (negative predictive value 85%). CONCLUSIONS: The diagnosis of an initial episode of pneumocystis pneumonia can be confidently made in a large proportion of immunosuppressed patients with respiratory symptoms on the basis of clinical symptoms, the absence of prophylaxis, chest radiographic appearances, and oxygen desaturation during exercise as shown by oximetry. Using these simple features clinicians can rapidly assign patients to the appropriate type of management at presentation. PMID- 1494762 TI - Bioelectric properties of cystic fibrosis airways obtained at heart-lung transplantation. AB - BACKGROUND: The basic defect in cystic fibrosis centres on abnormal ion transport in affected tissues such as the respiratory tract. Heart-lung transplantation provides a limited supply of native lower airways from these patients. The feasibility of in vitro studies of bioelectric properties and ion fluxes in lower airways, obtained at heart-lung transplantation from patients with cystic fibrosis, has been assessed. Comparison was made with airways from patients without cystic fibrosis. METHODS AND RESULTS: Tissue segments were mounted in Ussing chambers under open circuit conditions. The basal potential difference in tissues from nine patients with cystic fibrosis was -3.6 mV (SE 0.3 mV), not different from tissues from 12 patients without cystic fibrosis of -3.6 mV (0.5 mV). Amiloride (10 microM) caused a significantly greater fall in potential difference in bronchi from patients with cystic fibrosis (83.5% (SE 2.9%)) than in those from controls (55.1% (7.1%)). Isoprenaline (100 microM) produced no significant change in bioelectric properties in non-cystic fibrosis tissues, but induced a 26.2% (6.3%) increase in potential difference in cystic fibrosis airways. The latter response was reduced by amiloride pretreatment. Mucosal chloride substituted Krebs-Henseleit solution caused no change in bioelectric properties in cystic fibrosis airways. Sodium substituted Krebs solution produced a substantial fall in potential difference similar in magnitude to that seen after amiloride. Isotropic flux measurements showed no significant differences between non-cystic fibrosis and cystic fibrosis airways. No net movement of Na+ or Cl- was detected under open circuit conditions in either group. CONCLUSIONS: Cystic fibrosis bronchi obtained at heart-lung transplantation provide a viable source of tissue for in vitro studies of bioelectric properties. The increased response to amiloride characteristic of the upper airways in cystic fibrosis is retained in these tissues, as is the reduced chloride conductance. Although no differences in isotopic fluxes were seen between non-cystic fibrosis and cystic fibrosis tissues, heavily infected airways from patients with cystic fibrosis may not be suitable for ion flux measurements. PMID- 1494763 TI - Notification of tuberculosis: how many cases are never reported? AB - BACKGROUND: Notification of tuberculosis is essential for local contact tracing and for assessing the national incidence of tuberculosis. The accuracy of notification figures is uncertain. This study examined the notification rates of all patients diagnosed as having tuberculosis at two hospitals in the East End of London over five years. METHODS: In a retrospective survey of all patients aged 16 years or more presenting with tuberculosis to the London Chest Hospital or the Royal London Hospital from 1 January 1985 to 31 December 1989, cases of tuberculosis were identified from microbiology and histology records, statutory notifications, necropsy reports, coroners' records, hospital activity data, and death certificates. Clinical data were obtained from case notes and notification was determined from the local authority notification lists. RESULTS: Six hundred and nine adult patients with tuberculosis were identified. Notes were available for 580 cases (95%), of which 426 (73%) had been notified. The proportion of cases notified varied according to the specialty of the clinician in charge of the patient at diagnosis. Patients with a past history of tuberculosis and those who died within one year were less likely to have had their tuberculosis notified. Age, race, and lack of microbial or histological confirmation of diagnosis did not influence the proportion of cases notified. One hundred and eighty five patients had smear positive sputum, but 25 of these cases (14%) were not notified. Eighty five patients who had presented with pulmonary tuberculosis did not have their disease notified; 20 (24%) had smear positive sputum. CONCLUSIONS: Many cases of tuberculosis are not notified (27%). Fourteen per cent of all sputum smear positive cases of tuberculosis were not notified, and these patients are a considerable public health risk. The true incidence of tuberculosis in the area studied is at least one third higher than current notification figures suggest. PMID- 1494764 TI - Development of a shuttle walking test of disability in patients with chronic airways obstruction. AB - BACKGROUND: The aim was to develop a standardised and externally paced field walking test, incorporating an incremental and progressive structure, to assess functional capacity in patients with chronic airways obstruction. METHODS: The usefulness of two different shuttle walking test protocols was examined in two separate groups of patients. The initial 10 level protocol (group A, n = 10) and a subsequent, modified, 12 level protocol (group B, n = 10) differed in the number of increments and in the speeds of walking. Patients performed three shuttle walking tests one week apart. Then the performance of patients (group C, n = 15) in the six minute walking test was compared with that in the second (modified) shuttle walking test protocol. Heart rate was recorded during all the exercise tests with a short range telemetry device. RESULTS: The 12 level modified protocol provided a measure of functional capacity in patients with a wide range of disability and was reproducible after just one practice walk; the mean difference between trial 2 v 3 was -2.0 (95% CI -21.9 to 17.9) m. There was a significant relation between the distance walked in the six minute walking test and the shuttle walking test (rho = 0.68) but the six minute walking test appeared to overestimate the extent of disability in some patients. The shuttle test provoked a graded cardiovascular response not evident in the six minute test. Moreover, the maximal heart rates attained were significantly higher for the shuttle walking test than for the six minute test. CONCLUSIONS: The shuttle walking test constitutes a standardised incremental field walking test that provokes a symptom limited maximal performance. It provides an objective measurement of disability and allows direct comparison of patients' performance. PMID- 1494765 TI - Effect of aminophylline on brain tissue oxygenation in patients with chronic obstructive lung disease. AB - BACKGROUND: It is known that theophylline reduces cerebral blood flow in humans. To quantitatively assess the possible adverse effect of theophylline on brain tissue oxygen tension (PO2) due to decreased cerebral blood flow, two sets of experiments were conducted in mildly hypoxaemic patients with chronic obstructive lung disease. METHODS: Firstly, internal jugular venous PO2 (PjO2) was measured simultaneously with arterial and mixed venous blood PO2 (PaO2 and PvO2) during right heart catheterisation in 10 subjects (mean PaO2 73 mm Hg; conversion factor: 10 mm Hg = 1.33 kPa)) before and after intravenous infusion of aminophylline (6 mg/kg). The PjO2 and PvO2 were considered to reflect the average tissue PO2 for the brain and for the whole body respectively. Secondly, the relation between PaO2 and PjO2 over a wide range, with the PaCO2 similar to that in the first study, was investigated in a different group of 12 subjects by stepwise changes in inspiratory gas composition. RESULTS: The mean PjO2 decreased by as much as 6 mm Hg 15 minutes after an infusion of aminophylline, whereas PaO2 stayed at the same level and PvO2 showed only a small decrease. The low PjO2 value of 29 (SD 6) mm Hg with aminophylline in the first study was similar to the PjO2 value of 30 (2) mm Hg obtained during severe hypoxia (PaO2 45 mm Hg) in the second study. The coefficient of oxygen delivery for the brain decreased by 29% with aminophylline treatment, but did not change significantly during severe hypoxic challenge. CONCLUSIONS: These data suggest that an infusion of aminophylline lowers brain tissue PO2 appreciably when given to mildly hypoxaemic patients with chronic obstructive lung disease. PMID- 1494766 TI - Lung function abnormalities in repaired oesophageal atresia and tracheo oesophageal fistula. AB - BACKGROUND: Respiratory complications are common after neonatal repair of oesophageal atresia and tracheo-oesophageal fistula. The prevalence of lung function abnormalities and the relation between gastrointestinal complications and lung function has not been studied in a large number of patients. METHODS: Lung volumes and flow-volume loops were measured in 155 patients without spinal curvature aged 6-37 years who had undergone surgery for oesophageal atresia and tracheo-oesophageal fistula. RESULTS: Sixty four of the 155 patients had evidence of mild lower airways disease, with values for FEV1 more than two standardised scores below the predicted value in 39 (25%) and above 2 standardised scores for the residual volume (RV)/total lung capacity (TLC) ratio in 64 (41%). Restrictive lung disease (TLC more than 2 standardised scores below predicted) was present in 28 (18%). Severe lung function abnormalities were present in under 10% of the 155. Half the subjects had some evidence of extra-thoracic tracheal obstruction, with a high ratio of expiratory to inspiratory flow for peak flow in 76 (50%) and at 50% of vital capacity in 59 (38%). Patients with radiological gastro oesophageal reflux in early childhood had more airways obstruction and smaller lung volumes. Patients with current gastrointestinal symptoms were similar in their lung function to symptom free patients. CONCLUSIONS: Minor lung function abnormalities are common in patients after repair of oesophageal atresia. Early diagnosis and management of gastro-oesophageal reflux may help to minimise these lung function abnormalities. PMID- 1494768 TI - Alveolar atypical hyperplasia in association with primary pulmonary adenocarcinoma: a clinicopathological study of 10 cases. AB - BACKGROUND: A distinctive cytologically atypical lesion has been found in patients with primary adenocarcinoma of the lung. The aim of this study was to characterise the lesion and assess its role in tumour pathogenesis. METHODS: Lung parenchyma from 175 consecutive resection specimens for primary pulmonary adenocarcinoma were examined. Foci of atypical hyperplasia were identified. Cell proliferation state and expression of S100 and carcinoembryonic antigens were evaluated by immunohistochemistry. Clinical data on cigarette smoking and occupational exposure to carcinogens were abstracted from inpatient case notes. RESULTS: Ten cases (5.7%) with these distinctive cytologically atypical lesions were identified. The lesions showed immunohistochemical evidence of increased cell proliferation and focal carcinoembryonic antigen expression. The associated adenocarcinomas were of peripheral (parenchymal) type. There was an association with cigarette smoking and two of the 10 patients had synchronous carcinomas elsewhere in the lung. CONCLUSION: The clinical and pathological associations of these lesions suggest that they may be important in the histogenesis of primary pulmonary adenocarcinoma. PMID- 1494767 TI - Interstitial pulmonary fibrosis with and without associated collagen vascular disease: results of a two year follow up. AB - BACKGROUND: Interstitial pulmonary fibrosis is a disease with a highly variable clinical course. To ascertain if an inadequate selection of patients might explain part of this variability, two different groups of patients with interstitial pulmonary fibrosis, those with the "lone" form of the disease (LIPF) and those with associated collagen vascular disorders (AIPF), were studied separately. METHODS: Twenty consecutive patients (nine with LIPF and 11 with AIPF) were included. Their clinical and radiographic findings and results of pulmonary function tests, gallium-67 lung scanning, and cellular analysis of bronchoalveolar lavage fluid were compared at diagnosis. Moreover, the evolution of LIPF and AIPF was contrasted after a follow up of two years, both groups having received a similar treatment regimen of corticosteroids. RESULTS: At enrollment, patients with LIPF and AIPF were of similar age, and had similar symptoms and derangement of lung function, but patients with LIPF presented with finger clubbing, more obvious radiographic abnormalities, and a greater percentage of eosinophils in bronchoalveolar lavage fluid. Two years later, patients with LIPF had significantly decreased FVC, FEV1, TLC, TLCO, and PaO2. By contrast, lung function remained unaltered in patients with AIPF. Similarly, when the percentage change from entry to the study was compared, patients with LIPF showed a significant decrease in FVC, FEV1, and PaO2. CONCLUSIONS: Unlike the patients with AIPF, those with LIPF showed a deterioration in lung function and developed further restrictive impairment and poorer gas exchange. This has implications in their clinical management. PMID- 1494769 TI - Immune responses to colophony, an agent causing occupational asthma. AB - BACKGROUND: Inhalation of fumes from heated colophony (pine resin) is a recognised cause of occupational asthma, although the mechanisms by which colophony produces symptoms are unclear and specific immune responses to colophony have not been reported in sensitised workers. A study was carried out to determine whether colophony is antigenic. METHODS: The immune responses to colophony were studied in C57BL/6 mice and Dunkin Hartley guinea pigs after intraperitoneal injection of colophony conjugated to bovine serum albumin (BSA) or human IgG by a mixed anhydride procedure. Colophony and dinitrofluorobenzene were also compared in an assay of dermal sensitisation. RESULTS: Mice immunised with the colophony conjugates produced antibodies which recognised conjugates of both BSA and human IgG irrespective of which had been used as the immunogen. Solutions of unconjugated colophony inhibited the binding of antibodies to the BSA-colophony and BSA-abietic acid conjugates, confirming that the antibodies recognised one or more components in the colophony. Portuguese colophony also abrogated the antigen binding of serum from guinea pigs immunised with the BSA colophony conjugate. Spleen cells from immunised mice proliferated in the presence of the conjugates. Although there was some cross reactivity in these responses, it was not as marked as in the antibody assays. Unconjugated colophony failed to induce an immune response when injected intraperitoneally with adjuvant. Skin sensitisation could not be induced in mice by topical application, or by subcutaneous or intradermal injection of unconjugated colophony. CONCLUSIONS: Colophony components have the potential to act as haptens and an immune component could be involved in the pathogenesis of occupational asthma in workers exposed to colophony. Colophony is not readily immunogenic unless conjugated ex vivo to proteins. PMID- 1494771 TI - Use of jet mixing devices with an oxygen concentrator. AB - Jet mixing devices ("Venturi" devices) can be used in conjunction with domiciliary oxygen concentrators and provide delivered oxygen concentrations similar to those obtained with medical oxygen, though with the devices delivering higher concentrations (above 30% oxygen) the total flow is substantially reduced. A jet mixing device driven by a domiciliary concentrator would be valuable in various circumstances, especially in developing countries and also for infants and for patients with upper respiratory tract infections who are breathing through the mouth. PMID- 1494770 TI - Sex differences in hypokalaemic and electrocardiographic effects of inhaled terbutaline. AB - BACKGROUND: Gender differences in the chronotropic effects of infused isoprenaline have previously been described. The aim of the present study was to investigate possible gender differences in hypokalaemic, chronotropic, and electrocardiographic effects of inhaled terbutaline. METHODS: Twenty healthy volunteers (10 female) were recruited (mean age 24 years for women (F) and 22 years for men (M). Subjects were given either inhaled terbutaline 5 mg or placebo in single blind, randomised crossover fashion and the following measurements were made for four hours after inhalation: (a) serum potassium concentration; (b) heart rate; (c) electrocardiographic sequelae (T wave amplitude, Q-Tc interval). The effects of terbutaline on serum potassium was chosen as the primary end point for detecting a 0.3 mmol/l difference between sexes, with a beta error of 0.2 and alpha set at 0.05. RESULTS: The hypokalaemic effects of terbutaline were significantly greater in women, the potassium results (means and 95% CI) being as follows: lowest potassium concentration--F 3.12 (2.96-3.28) mmol/l v M 3.65 (3.49 3.81) mmol/l; percentage change from baseline at one hour--F 15.4% (11.5-19.3%) v M 8.5% (4.6-12.3%); average potassium concentration during the four hours--F 3.39 (3.33-3.46) mmol/l v M 3.78 (3.72-3.85) mmol/l. There was no significant regression between body weight and the potassium response to terbutaline. There were also significant sex differences for T wave, Q-Tc, and heart rate response. The percentage fall in T wave amplitude 30 minutes after terbutaline was: F 44.6% (32.1-57.0%) v M 22.4% (9.9-34.8%). CONCLUSIONS: Women are more sensitive to the hypokalaemic, chronotropic, and electrocardiographic sequelae of inhaled terbutaline. PMID- 1494773 TI - Preoperative laser therapy in a patient with resectable bronchogenic carcinoma and severe coronary artery disease. AB - A 67 year old man with severe coronary artery disease was found to have a resectable bronchogenic carcinoma. Myocardial revascularisation and lung resection were considered to be unduly hazardous as either separate or combined operations. Preoperative laser therapy, however, enabled the two procedures to be performed in greater safety in the most appropriate sequence. PMID- 1494774 TI - Multiple cystic pulmonary hamartomas. AB - A patient with multiple cystic hamartomas presented with a pneumothorax and later developed a cystic myxomatous vaginal polyp. This and three of the cysts were resected. She remains well 13 years later. Multiple cystic hamartomas are uncommon and may be misdiagnosed as pulmonary metastases. PMID- 1494775 TI - Pneumothorax secondary to septic pulmonary emboli in tricuspid endocarditis. AB - Two cases of pneumothorax secondary to pulmonary septic infarctions occurred in the course of tricuspid endocarditis in intravenous drug misusers. This unusual complication must be considered in patients with right sided endocarditis who develop pleuritic chest pain, haemoptysis, or breathlessness. PMID- 1494776 TI - Congenital bronchial atresia with regional emphysema associated with pectus excavatum. AB - Two cases of congenital bronchial atresia with pectus excavatum are reported. Costosternal retraction during the efforts to overcome the airway obstruction due to encroachment on normal lung tissue by the hyperinflated segments may play a part in causing pectus excavatum. PMID- 1494772 TI - New perspectives on basic mechanisms in lung disease. 1. Lung injury, inflammatory mediators, and fibroblast activation in fibrosing alveolitis. AB - It is over 25 years since Scadding first defined the term fibrosing alveolitis. It has since been established that complex mechanisms underlie its pathogenesis, including epithelial and endothelial injury, vascular leakage, production of inflammatory cells and their mediators, and fibroblast activation. Only through a detailed knowledge of how these cellular and molecular events are interlinked will we learn how to combat this disease, which is notoriously resistant to present treatments. So far the only therapeutic advances have been refinements in immunosuppression, and even these treatments are frequently disappointing. We believe that future advances in treatment will come from the development of agents that protect endothelial and epithelial cells from further injury and agents that can inhibit release of inflammatory mediators. A better knowledge of the mechanisms of collagen gene activation and the biochemical pathways of collagen production may also allow the identification of vulnerable sites at which new treatments may be directed. A combined approach to modifying appropriate parts of both the inflammatory component and the fibroblast/collagen component should provide a new stimulus to research. Further epidemiological studies are also needed to identify the environmental causes of lung injury that initiate the cascade of events leading to interstitial fibrosis. PMID- 1494777 TI - Inhaled corticosteroids: benefits and risks. PMID- 1494778 TI - Recent developments in the management of the pulmonary complications of HIV disease. PMID- 1494779 TI - Lymphocyte and lymphocyte subset numbers in blood and bronchoalveolar lavage and pleural fluid in various forms of human pulmonary tuberculosis. PMID- 1494780 TI - Barcelona's asthma epidemics. PMID- 1494781 TI - Randomised clinical trial of chest drainage systems. PMID- 1494782 TI - Variability of inspired oxygen concentration with nasal cannulas. PMID- 1494784 TI - Methodological problems relating to the evaluation of anti-rejection treatments. AB - The evaluation of anti-rejection treatments raises a variety of methodological problems depending on the clinical phase of development. The first administrations in man are carried out in order to study the profile of a drug and are sometimes performed in healthy volunteers, but more frequently in transplanted patients. It is then necessary to select and evaluate the assessment criteria which will be used in comparative studies to demonstrate the efficacy and safety of the new treatments compared with reference drugs. Factors responsible for variation may be related to the nature of the organ transplanted, the clinical condition of the donor and host and their immune compatibilities. Associated treatments and the multidisciplinary environment in which an organ transplant takes place should also be taken into consideration. After registration, knowledge about the new anti-rejection drug continues in order to identify the optimum conditions for its use, its true therapeutic efficacy and to determine possible new indications. PMID- 1494783 TI - The use of the nose to study the inflammatory response of the respiratory tract. PMID- 1494785 TI - [Hepatic allograft rejection. Diagnostic and therapeutic aspects]. AB - Rejection is still a major problem in liver transplantation: 50-70% of patients present at least one acute episode, while 5-15% develop chronic rejection. Acute rejection is suggested by clinical signs and abnormal laboratory test results, but only histological signs on biopsy specimens are adequately specific. The three most frequent elementary lesions are a portal infiltrate, bile duct alterations and endothelial inflammation. Several systems have been forwarded to classify the degree of rejection. Chronic rejection is characterized by a progressive reduction in the number of interlobular bile ducts. It does not respond to available immunosuppressive drugs and thus requires retransplantation. Prophylactic immunosuppression is usually based on the triple-drug combination cyclosporine/azathioprine/corticosteroids. The orthoclone OKT3 and FK506 have recently been proposed for prophylactic use in this setting. Treatment of liver graft recipients with cyclosporine carries a number of specific disadvantages, particularly with regard to gastrointestinal interactions (delayed intestinal absorption in patients with cholestasis, bile derivation, diarrhea or receiving cholestyramine; possibility of a sharp increase in blood cyclosporine levels when the Kehr drain is clamped), and drug interactions (cyclosporine metabolization of CP450-IIIA accounts for most such interactions). The results of radioimmunoassay and TDx must be interpreted with care, and HPLC remains the reference technique in borderline cases. Cyclosporine is hepatotoxic in about 20% of cases, generally giving rise to cholestasis. This toxicity is dose-dependent and therefore diminishes when the dosage is reduced. Most groups initially treat rejection with corticosteroids. The response to treatment is generally evaluated in terms of liver function tests.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1494786 TI - [Rejection reaction. Elements of diagnosis, monitoring, therapeutic attitude in the case of kidney]. AB - Allograft rejection reaction must be integrated in the broader sense of alloreactivity, i.e. involving a huge T cell repertoire with a high number of alloreactive precursors. This reaction is modulated by the particular immunological state induced by chronic renal insufficiency, by haemodialysis and by the primary kidney disease. The imperfect effect of current immunosuppressive drugs is illustrated by a sizeable proportion of grafts undergoing a chronic rejection process where many growth factors are involved. It has to be noted that allostimulating cells are different from target cells. At present, the therapeutical rejection involves corticosteroids and serotherapy, but it is hoped that new immunosuppressive drugs will increase the efficacy of the rejection crisis treatment. PMID- 1494787 TI - [Acute cardiac graft rejection after orthotopic cardiac transplantation. Elements of diagnosis and monitoring, therapeutic attitude]. AB - The diagnosis of acute rejection in heart allograft recipients receiving cyclosporine is still an important challenge. The poor diagnostic value of clinical signs and the ECG means that regular endomyocardial biopsies must be performed. Despite their diagnostic value during the first year after transplantation, endomyocardial biopsies are less sensitive there after and currently suffer from the lack of a universally accepted histological classification. Doppler echocardiography can be used for routine surveillance and has proven reliable for the diagnosis of acute rejection with various clinical presentations when used in conjunction with endomyocardial biopsies. Immunohistological examination of myocardial specimens can further increase the sensitivity of histological diagnosis. Similarly, immunoscintigraphy with indium 111-labelled antimyosin antibodies is of value for the prediction of acute rejection after the first year. Therapeutic approaches have been standardized, but must still be tailored to the individual patient according to the severity of the rejection and the presence of associated infection and/or metabolic disturbances. PMID- 1494788 TI - Monoclonal antibodies in human organ transplantation and auto-immune diseases. AB - The usefulness of monoclonal antibodies (mAbs) in the transplantation field has become evident over the last couple of years. Different mAbs have been used as a prophylactic treatment after transplantation, in a therapeutic way against acute organ rejection and new diagnostic tools to predict clinical rejection immerge. One can even hope that with humanised mAbs or human mAbs obtained by repertoire cloning the formation of human anti-mouse antibodies will be solved although on the one hand this appeared not to be a big problem and on the other hand anti idiotypic antibodies can still be expected. However, the most puzzling question is how the mAbs modulates the immuno-response and this not only in organ rejection but also in auto-immune diseases. Only one out of many CD25 mAbs with seemingly similar epitope recognition can be used in therapeutical treatment of acute Graft versus Host Disease. The same mAb is not, however, very efficient in the prophylactic treatment of kidney transplantation without association of suboptimal doses of cyclosporin A. Another example is a CD4 mAb which is efficient in the treatment of polyarthritis with no side effects but which provokes transient but clear side effects when used in psoriasis or multiple sclerosis patients. A second CD4 mAb with high inhibitory activity in several bioassays compared to the first CD4 mAb has no beneficial effect at all on polyarthritis. Also the question why there is a percentage of "no response" patients among apparently identical "good response" patients remains unanswered. However it becomes clear from these experiences that: 1) mAbs recognizing a similar epitope and being of the same isotype will not automatically have the same effect in therapy. 2) side effects may be depending of the disease treated. 3) the activities of mAbs in bioassays and even animal models very often do not reflect the in vivo situation in human. 4) efficiency of the treatment with mAbs can be increased by a better understanding of the mode of action and increased efficiency can be expected by association of several mAb or mAb with drugs for the "no response" patients and should be the next step in the therapeutical use of mAbs. PMID- 1494789 TI - [Modalities of therapeutic follow-up of cyclosporine]. AB - The therapeutic use of cyclosporine (CsA) requires total blood levels to be monitored with a specific assay, since this drug is nephrotoxic, has a narrow therapeutic index, shows wide intra- and inter-individual differences in its pharmacokinetic behaviour and can interact with other drugs. The parameter generally measured is the residual blood concentration at equilibrium; levels are occasionally again measured four or six hours after CsA administration. Patients are monitored every two days during the first two weeks following organ transplantation, a frequency which gradually declines to monthly determinations at four to six months in the absence of complications. The therapeutic range of blood CsA concentrations is still poorly defined. In renal, liver, heart and bone marrow transplantation most authors recommend concentrations of 100-250 ng/ml for the first three months when renal function is satisfactory. Ways of administration (i.e. continuous infusion or dividing up of the daily dose) must be taken into consideration to assess values of blood concentration of CsA. PMID- 1494790 TI - [Lymphocytic molecules implicated in rosette phenomenon. Differential effect of antilymphocyte serum on T (CD2+E2+) and B (CD2-E2+) lymphocytes]. AB - The molecule E2 is present on T lymphocytes and thymocytes and is implicated in rosette phenomenon most probably via interaction with CD2. The discrepancy observed between rosette levels and lymphocyte phenotypes in the follow-up of kidney-transplanted patients treated with antilymphocyte globulins (ALG), methylprednisolone and azathioprine leaded us to study the effect of ALG on E2 molecule. PMID- 1494791 TI - [Justification of the therapeutic follow-up of cyclosporine]. PMID- 1494792 TI - [Circulating forms of cyclosporin A]. AB - The major circulating blood fraction of cyclosporin is localized in red blood cells. It is 58% for blood levels of less than 1,000 ng/ml. Beyond this concentration, a fall of this percentage is noticed which is related to a saturation phenomenon which occurs in its binding on an intracytosol protein, cyclophilin. Other fractions are distributed in the following manner: 27.5% on lipoproteins, 5% on albumin, 4% on polymorphonuclears, 5% on lymphocytes and 0.5% in the free state. There are various binding sites in the lymphocyte: in the membrane, cytosol on cyclophilin, and on the nucleus. The manner of binding on various plasma proteins, blood cells and platelets results in manifold pharmacological, pharmacokinetical, and toxicological results which are discussed here. PMID- 1494793 TI - [Methods of cyclosporine determination in biological media]. AB - Cyclosporine is an immunosuppressive medicine widely used in all grafts and organ transplantations. Its pharmacokinetic characteristics, especially its intensive metabolism, result in great variability potential between and within patients justifying blood levels' determination in patients treated with this drug. If the biological medium (whole blood) selection is of the utmost importance regarding the quality of the result and its validity, the accuracy of the result compared to the blood levels of the drug will depend on the selection of the determination technic involved. At present, various analytical methodologics are available: the immunological technics involving radioactive or non-radioactive tracers, and HPLC (High Performance Liquid Chromatography) technic. The latter requires good chromatography experience; it takes more time to be implemented due prior extraction of cyclosporine from the biological media. This extraction can be effected with organic solvents or by column chromatography: these various technics will be discussed and compared. This methodology enables one to determine metabolite concentrations. Regarding immunological technics, multiclonal or monoclonal antibodies are available for technics involving fluorescence polarization. However, for radioactive tracings and enzymic tracers, only one specific antibody is available. It is important to take into account the specificity of these antibodies relative to the various metabolites regarding results interpretation, their crossing rate being altered in accordance with antibodies and related pathologies. The validity of these technics will be discussed in words of accuracy and exactitude. The laboratory arrangement, the feasability and cost of the technic are also factors to be taken into consideration. At present selection tends towards to most specific technics. PMID- 1494794 TI - [Critical analysis of the immunosuppressive activity and of the toxicity of cyclosporine metabolites]. AB - Cyclosporin A (CyA) is intensively metabolized by the hepatic cytochrome P450 III monooxygenases A systems in the human liver. Among about twenty metabolites, only twelve of which have been identified, and found in the blood of treated patients. The major metabolic pathways are hydroxylation and N-demethylation of the various amino-acids of the parent compound. Quantitatively, and although there are some differences depending on whether one refers to the residual concentration or to the Area Under Curve (AUC), major metabolites are always, in decreasing significance, M17, M1, M18, and M21. Metabolite/CyA ratio is subjected to numerous variations from one patient to another which can be explained by pharmacogenetics, but can also be affected by the type of graft, the hepatic performance status, and related treatments. Be that as it may, it is metabolites 17 and 1 which are especially present in the blood in large quantities. In fact, if one considers the relative percentage of metabolites in comparison with CyA, expressed in blood AUC, values of 79, 39, 21 and 15% are noticed for M17, M1, M18, and M21, respectively. These percentage become 170, 65, 16 and 10% if one refers to residual concentration. In the aggregate, these results may be extrapolated to the tissues and it has been shown that, excepting the liver which contains high M17 concentrations, metabolites overall appear in equal or lower levels than CyA. They are widely diffused throughout the tissues and the highest levels are found in the liver and kidneys, then in fats and pancreata.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1494795 TI - [Therapeutic follow-up of cyclosporine. Main factors involved in the interpretation of results]. AB - The therapeutic drug monitoring of cyclosporine (CsA) requires not only correct methodological conditions but also taking into consideration of numerous other factors involved in the value of blood drug concentrations. Main factors concern: the clinical state of patients. Liver function and bile flow act predominantly on drug clearance; the choice of monitoring parameters and of sampling time. Comparison was done of information given respectively by area under the curve and different sampling times. Usually blood concentration is monitored with trough level plus eventually another concentration measured 4-6 h after drug administration; the time-table. Blood concentrations are measured at steady-state period. Bioavailability of CsA increases in the immediate postoperative period after transplantation; ways of CsA administration. Trough level is influenced by dividing up of the daily dose. In case of continuous i.v. infusion mean blood concentration, but not trough concentration, is measured; drug interactions. Several drugs modify blood concentrations of CsA. Others induce an additive nephrotoxicity or immunosuppressive effect. Recommended blood trough concentrations vary with clinical indications, experience and therapeutic habits of each transplant center. Currently recommended values (CsA whole blood concentration determined by specific method) are 150-250 ng/ml in renal, heart, liver and bone marrow grafts, during the 3 months after transplantation, with good renal function. Concentrations are often higher for lung transplantation. PMID- 1494796 TI - [Cyclosporine. Obscure sides of cardiac and pulmonary transplantations]. AB - Cyclosporine therapy after heart and lung transplantation implies a number of specific aspects such as: kidney deficiency associated to heart failure, which delays its use as for cardiac transplantation; intestinal absorption disturbances that could be linked to the cystic fibrosis disease for lung transplantation. For both types of transplantation, local efficiency could indicate an interesting, but still unexplored therapeutic effect. Finally, it seems that the immunosuppressive effect could be linked to important pharmacological effect on calcium and could explain the specific aspects of rejection of patients under cyclosporine. PMID- 1494797 TI - [Therapeutic follow-up of cyclosporine: specific problems in kidney, liver, bone marrow grafts and in the treatment of autoimmune diseases]. AB - In transplantation, the advantage of therapeutical follow-up of immunosuppressive treatment involving cyclosporine is generally recognized, even though the ideal therapeutic index has as yet not been perfectly defined. Cyclosporine blood level determination is merely one factor among many others in therapeutical success, but if replaced in its context, can provide valuable and relevant information. A certain number of rules exist regarding the use, and pharmacological surveillance, of cyclosporine in all patients treated with this medicine. These rules take into consideration the patients immunological responsivity, the length of time since transplantation, the position of cyclosporine in immunosuppressive treatment, related pathologies and medicines. However, it is of special interest to consider a few points according to the nature of the indication. In kidney transplantation, and nephrotoxicity, determination of cyclosporine blood level will help differential diagnosis between an immunological origin (graft rejection) and an iatrogenic origin; in liver transplantation the consideration of metabolite determination, and study of metabolite ratio, will enable the gathering of information on performance status and toxicity hazards. In some cases, the necessity to administer intravenous cyclosporine, and the special weakness of some patients as in bone marrow transplantation, treatment surveillance patterns will be altered. Finally in spite of our lack of background information, the use of cyclosporine in autoimmune diseases has shown that principles of treatment and surveillance differed from one pathology to another, this being increased in some cases (juvenile diabetes), or occasional and even non-essential (psoriasis). PMID- 1494798 TI - [Critical analysis of drug interactions with cyclosporine. Evaluation of interactions with cyclosporine]. AB - Cyclosporine A is a potent immunosuppressive agent, widely used in organ transplantation, in bone marrow transplantation and in the treatment of some autoimmune diseases. Changes of its absorption, a metabolism mainly processed by the liver and a concentration-related nephrotoxicity lead to the need of a careful drug monitoring, allowing to obtain blood levels that must be low and nevertheless sufficiently efficient. Cyclosporin A may additionally yield some numerous drug interactions. Those with potentially serious issue must be mandatory avoided and distinguished from those less severe that only have to be followed up. The strategy differs according to the nature of the interaction (i.e. pharmacokinetic/pharmacodynamic): the posology will have either to be adjusted or the risk/benefit ratio will have to be taken into account to decide any change in the dosage regimen. PMID- 1494799 TI - [Monitoring of clinical trials and interim analysis. 1. Monitoring committee]. AB - In order to fulfil the ethical principles linked to the protection of patients randomized in a controlled clinical trial, monitoring procedures need to be set up. In this context, a committee of experts, called the data monitoring committee is in charge of reviewing regularly unblinded data to assess the quality and the relevance of the trial, to evaluate the evidence of an emerging treatment difference and to control the rate of occurrence of serious adverse events. After each meeting, the monitoring committee reports to the steering committee its recommendation to continue or to stop the trial prematurely. Protocol modifications might be proposed as well. Illustrated with several examples, this article reviews different situations a monitoring committee might have to tackle with. PMID- 1494800 TI - [Monitoring of clinical trials and interim analysis. 2. Statistic methods]. AB - Although the decision to continue or to stop prematurely a clinical trial is not solely based on statistical tests, they bring useful objective arguments to the data monitoring board. However, the multiple use of statistical tests leads to increase the risk of false positive conclusions in favor of one of the treatments, and several methods have been developed to address this problem. This article presents the four major strategies that are being used for monitoring clinical trials, as well as the rationale for planning and using such statistical monitoring procedures. PMID- 1494801 TI - Clinical usefulness of estrogen receptor immunocytochemistry in human breast cancer. AB - We assessed the reliability of the immunocytochemical assay of estrogen receptor (ER-ICA) as a marker of clinical outcome. Relapse-free interval (RFI) and overall survival (OS) according to ER-ICA status were retrospectively evaluated on a series of 210 patients who had undergone surgery for primary breast cancer between January 1985 and December 1988. ER assay by the dextran-coated charcoal method (DCC) was also performed in 189 tumors. A significant positive correlation was found between the DCC and ER-ICA assays, with an overall agreement of 79%. ER ICA status showed a prognostic predictive power with respect to OS and RFI in the whole series of patients and in the subset of node-positive patients. It was also a marker of outcome with respect to OS in the subsets of node-negative patients and patients with tumors < or = 2 cm in diameter. Moreover, the predictive value of the ER-ICA assay was higher than that of the DCC assay in the present study. These findings emphasize the clinical usefulness of the ER-ICA assay as a measure for prognosis. PMID- 1494802 TI - Quality control for colposcopy in the Florence screening program for cervical cancer. AB - The authors report on the quality control for colposcopy adopted in the Florence District screening program. The sensitivity of colposcopy was determined on all cases of CIN III recorded in the local cancer registry in a four-year period. However although this showed that a centralized colposcopic clinic employing a limited number of expert operators is superior to the performance of colposcopy in private practice, such a parameter was impractical for further routine quality control since differences among operators were too small and statistically insignificant. Other parameters for quality control were chosen, namely a) the rate of colposcopically directed biopsies performed, b) the detection rate of CIN II or more severe lesions, and c) the positive predictive value of a directed biopsy for CIN II or more severe lesions. Analysis of these indicators after stratification by cytologic report allows the identification of those operators who need additional training and provides useful information for colposcopists to optimize their diagnostic and operative criteria. PMID- 1494803 TI - The effect of cytological screening on cervical neoplasia in the Italian province of Varese. AB - In the Varese province (409,142 female inhabitants in 1981), which has been covered by a cancer registry since 1976, cytologic screening for cervical cancer began in the early sixties in the municipality of Busto Arsizio (41,818 female inhabitants in 1981) and subsequently spread to the rest of the province. The distribution by age of cytologic smears and of detected in situ cancer reveals a more frequent attitude to be screened for women aged between 25 and 54 years. Overall, the incidence rate (world standardized) for invasive cancer in the province decreased from 10.3/100,000 women-year in the period 1976-81 to 7.5/100,000 in 1982-87. In Busto Arsizio a survey of the hospital archives has been carried out to identify the cases of cervical cancer diagnosed from 1966 to 1985: in this 20-year period, the incidence of cervical cancer decreased markedly, but only in those ages frequently screened. In the rest of the province, for the first period of cancer registration (1976-81), the incidence was significantly higher than in Busto Arsizio, especially for ages 35-64. Subsequently, between 1982-87, the cervical cancer incidence was low in both areas. For the period 1976-87, no difference for carcinoma in situ registration rates was observed between the two populations studied. Actually by 1976, when the Lombardy Cander Registry began its activity, the screening was diffuse throughout the province. These observations are consistent with the preventive effect of screening activity. PMID- 1494804 TI - Altered fractionation schedules in radiotherapy of head and neck cancer. A review. AB - The authors review the main contributions of international literature to show the current status in clinical trials on unconventional fractionations of the dose in radiotherapy of head and neck cancers. Several clinical (but only a few randomized) trials have been conducted over the last 15 years using hyperfractionated (HF), accelerated (AF) or mixed (HF-AF) schedules. HF schedules have obtained promising results in terms of local control in comparison with conventional fractionation (CF) of the dose. Improvement in survival was also obtained by the random trials of Pinto and Sanchiz, whereas in EORTC trial no. 22791, the improvement in survival rate was only marginal. A significant increase in local control and, less frequently, in survival has been claimed in several studies using HF-AF. Such data still need to be confirmed by a random study, since EORTC trial 22811 showed superimposable results in comparison with CF. Selection of the most suitable cases for altered fractionation schemes is also being studied in ongoing trials of the EORTC (22851) and RTOG (90-03). As regards acute reactions during and after altered fractionation, they are more severe than after CF. Only pure HF with a dose intensity approximately comparable to CF seems to produce similar acute reactions. Several factors have been found to influence the severity of acute mucosal reactions: interfraction interval, overall treatment time, total dose, and field size. As regards late damage, genuine HF schemes seem to cause roughly equivalent late damage in comparison to CF, whereas high-dose intensity schedules have a higher rate of complications. Interfraction interval, overall treatment time, total dose, fraction size and field size can influence the risk of late sequelae. Before altered fractionations can be considered standard therapy, more data are needed, which should be provided by multicentric randomized trials, some of which are already in progress. PMID- 1494805 TI - Accelerated hyperfractionation of radiotherapy for rapidly growing inoperable breast cancer unresponsive to chemotherapy. AB - Eleven patients with rapidly growing inoperable breast carcinoma were treated with a thrice-a-day fractionation of 1.2 Gy per fraction (5-h intervals, 15 fractions per week). Nine of them had been considered as non-responders to previous aggressive multidrug chemotherapy. A split of 2 weeks was inserted after 54 Gy, and radiation fields were then restricted to the clinical positive area up to a total tumor dose of 90 Gy. Nine of 11 patients completed their treatment, and 7 of them were considered as complete responders. Acute toxicity was surprisingly low (grade I-II). Four patients surviving 12-18 months after radiotherapy did not relapse and did not present any late complications. A favorably improved quality of life was obtained for all 9 patients. PMID- 1494807 TI - Phase I study of FUDR continuous infusion with circadian variability in advanced cancer patients. AB - A phase I study of floxuridine circadian infusion was performed in 14 patients with advanced solid tumors (9 colonic, 1 gastric, 4 renal). The starting dose was 0.15 mg/kg/day for 14 days followed by a 14-day therapy-free interval. Sixty eight percent of the daily dose was infused between 3pm and 9pm. The dose was increased by 0.025 mg/kg/day for each successive course. Eighty-one cycles of therapy were given for a total of 1134 days of treatment. The mean dose intensity was 0.868 mg/kg/day for the entire group. The highest dose achieved (maximum tolerated dose) was 0.325 mg/kg/day. The most frequent toxicity was diarrhea (4.9% of all courses) and nausea-vomiting (3.7% of all courses). These side effects were of a low grade and all were resolved without hospitalization. Our results suggest the circadian modulation of floxuridine infusion. PMID- 1494806 TI - Weekly first-line chemotherapy of metastatic breast cancer with cyclophosphamide and epirubicin. AB - Forty-six patients with metastatic breast cancer who had not received previous chemotherapy for advanced disease entered a phase II trial of weekly chemotherapy with cyclophosphamide (250 mg/m2) + epirubicin (25 mg/m2) for 16 weeks. The overall response rate was 61% (95% confidence limits, 47-75%), with 10 complete and 17 partial responses. Toxicity was mild and confined to nausea and vomiting and asymptomatic neutropenia (except in 2 cases). Sixty-three per cent of patients had no side effects. Weekly cyclophosphamide + epirubicin is an active and nontoxic regimen for patients with metastatic breast cancer who have had no prior anthracycline-containing adjuvant chemotherapy. PMID- 1494808 TI - Favorable response of metastatic adrenocortical carcinoma to etoposide, adriamycin and cisplatin (EAP) chemotherapy. Report of two cases. AB - The usefulness of non-specific chemotherapy for advanced adrenocortical carcinoma (ACC) is controversial. We report on 2 young female patients (25 and 19 yr) who presented with a clinical picture of Cushing's syndrome due to histologically confirmed ACC. The first patient underwent radical surgery, but after a disease free interval of 6 months a local recurrence was apparent. She was reoperated and treated with 6 courses of cisplatin and etoposide chemotherapy. Mitotane (8 g daily) was begun, but 2 months later debulking surgery was again performed. A second-line chemotherapy with the etoposide, adriamycin, cisplatin (EAP) scheme attained a partial remission lasting 7 months, then metastatic spread to the brain led to death of the patient. The survival time was 30 months. The second patient underwent radical surgery and adjuvant mitotane (4 g daily), but multiple lung and mediastinal metastases were diagnosed after an interval of 29 months. Chemotherapy with the EAP regimen (6 courses) without interrupting mitotane attained a partial remission lasting 21+ months. We suggest that the EAP scheme is active in advanced ACC and that its association with mitotane is feasible. PMID- 1494809 TI - Weekly doxorubicin chemotherapy for breast cancer in pregnancy. A case report. AB - The simultaneous occurrence of breast cancer and pregnancy is rare. Little data are available about cytostatic treatment in patients with breast cancer during pregnancy. We report on a 31-year-old woman with a 28-week pregnancy and a T3 N+ Mx breast cancer treated with weekly doxorubicin chemotherapy. This was a well tolerated treatment without toxicity or complications for the mother. A partial response of the tumor was observed after 4 treatment courses. A normal baby was delivered. Doxorubicin and its metabolites were not detected in amniotic fluid collected through amniocentesis. Macroscopic and pathologic examinations of the placenta were normal. Although larger experiences are needed, weekly doxorubicin seems to yield satisfactory results without additional risks of fetal distress or malformations when given in women during the second and third trimester of pregnancy. PMID- 1494810 TI - A case of malignant phyllodes tumor with muscular and fatty differentiations. AB - A 50-year-old female underwent surgical removal of a mammary phyllodes tumor, whose peculiar histologic feature was the coexistence of areas of liposarcoma and leiomyosarcoma. The morphologic differential diagnosis is briefly discussed. PMID- 1494811 TI - Hypertriglyceridemia during long-term interferon-alpha therapy: efficacy of diet and gemfibrosil treatment. A case report. AB - Interferon-alpha might increase triglyceride serum levels through the enhancement of hepatic lipogenesis and/or inhibition of the peripheral lipoprotein lipase. Hypertriglyceridemia during interferon-alpha therapy has been only recently described, mostly in patients with previous abnormalities of lipid metabolism. The authors report here a case of a 65-year-old male bearing advanced colon carcinoma who developed hypertriglyceridemia during long-term interferon-alpha treatment in association with 5 fluorouracil administration. Hypertriglyceridemia was maintained within acceptable levels, without adjusting the treatment plan, by an appropriate diet and gemfibrosil administration. PMID- 1494812 TI - Acute myelocytic leukemia and chronic myelomonocytic leukemia simultaneously with resectable breast cancer: a report of two cases. AB - This report describes 2 patients who developed acute myelocytic leukemia (AML) type M2 and chronic myelomonocytic leukemia (CMML) of the FAB classification, respectively 2 months and 2 weeks after diagnosis of operable breast cancer. The patient with AML showed pancytopenia 2 months before the diagnosis of AML, had a normal karyotype, and showed a good response to chemotherapy. The patient with CMML had a normal karyotype, and she was treated with hydroxyurea and supportive therapy. The 2 patients had no previous exposure to irradiation or cytotoxic therapy. These cases show that breast cancer and either leukemia or myelodysplastic syndrome may be associated even without previous irradiation or combination chemotherapy. PMID- 1494813 TI - Members. American Ophthalmological Society. PMID- 1494814 TI - Glaucoma in the Marfan syndrome. PMID- 1494815 TI - The classification of amblyopia on the basis of visual and oculomotor performance. PMID- 1494816 TI - Histopathology of the ICE syndrome. PMID- 1494817 TI - Management of late bleb leaks following glaucoma filtering surgery. PMID- 1494819 TI - Outcome of treatment for bilateral congenital cataracts. PMID- 1494818 TI - Ocular complications associated with cardiac transplantation. PMID- 1494820 TI - Progression and regression of partial corneal involvement in the iridocorneal endothelial syndrome. AB - We have observed three women with partial corneal involvement in the ICE syndrome for over 10 years. During this time, the peripheral anterior synechiae progressed in all three, with glaucoma developing in one patient. In two patients, the abnormal endothelial cells spread to cover the entire posterior corneal surface; in the third, they disappeared entirely (ie, "the ICE melted"). The endothelial permeability to fluorescein remained abnormally low only in the two eyes with diffusely abnormal endothelium, increasing to normal in the third eye as the abnormal endothelium disappeared. The permeability in that eye had been abnormally low only in the superior half of the cornea, where the abnormal endothelium was. As the abnormal endothelium regressed, it was replaced by normal endothelium with a normal cell density similar to that of the opposite, uninvolved eye. Thus, over a 10-year period the partial endothelial involvement associated with the ICE syndrome progressed substantially in two patients and regressed dramatically in a third. PMID- 1494822 TI - The study of malformations "by the company they keep". AB - Our study of individuals with thalidomide embryopathy reaffirms many of the principles of clinical teratology concerning sensitivity of developing structures and specificity of action. It also highlights important features of ocular teratology that differ from those of other organ systems. Because malformations of the eye and associated structures do not significantly threaten the survival of the embryo, fetus, or neonate, any variation in prevalence in older individuals is not due to the nature of the ocular malformation but may be significantly modified by "the company they keep," the systemic malformations occurring at the same time as the original insult, whether it be an environmental, a genetic, or a local disturbance. Additionally, the presence of clusters of malformations caused by a teratogen at a specific time supports the concept of a common pathogenic mechanism and provides suggested avenues for further research into the cause of these malformations. PMID- 1494821 TI - Initial experience with a new method of laser transscleral cyclophotocoagulation for ciliary ablation in severe glaucoma. PMID- 1494823 TI - Compensatory epithelial hyperplasia in human corneal disease. PMID- 1494825 TI - Indirect ophthalmoscope laser treatment as supplement to 125I plaque therapy for choroidal melanoma. PMID- 1494824 TI - Excimer laser photorefractive keratectomy in high myopia: a multicenter study. PMID- 1494826 TI - Aspergillus endophthalmitis: a clinical and experimental study. PMID- 1494827 TI - The blepharogram in Horner's syndrome. PMID- 1494828 TI - Botulinum alignment for congenital esotropia. AB - This is the first report of a group of patients with congenital esotropia examined for motor and sensory evidence of binocularity a minimum of 3 years after alignment by botulinum. Evidence for binocularity was clearly present in approximately one half of the patients. Lag time to satisfactory alignment was at least 1 month (average, 5 months) following the initial botulinum injection. The results must be considered preliminary. However, when these results are compared with those of patients with congenital esotropia aligned by incisional surgery by age 2 years and examined with the same testing devices by this same investigator, botulinum alignment appears to be less effective than surgical alignment in establishing evidence for binocularity (P < 0.005). PMID- 1494829 TI - The four-meter confrontation visual field test. AB - The 4-m confrontation visual field test has been successfully used at the Mayo Clinic for many years in addition to the standard 0.5-m confrontation visual field test. The 4-m confrontation visual field test is a test of macular function and can identify small central or paracentral scotomas that the examiner may not find when the patient is tested only at 0.5 m. Also, macular sparing in homonymous hemianopias and quadrantanopias may be identified with the 4-m confrontation visual field test. We recommend use of this confrontation visual field test, in addition to the standard 0.5-m confrontation visual field test, on appropriately selected patients to obtain the most information possible by confrontation visual field tests. PMID- 1494830 TI - Color Doppler imaging identifies four syndromes of the retrobulbar circulation in patients with amaurosis fugax and central retinal artery occlusions. PMID- 1494832 TI - The ocular manifestations of sickle-cell disease: a prevalence and natural history study. AB - Prophylactic photocoagulation may have a role in the treatment of proliferative sickle retinopathy in selected patients with SC disease, but none of the studies reported to date have established that such treatment of these eyes improves the long-term visual outcome as compared with the natural history as documented in this study. The similar visual outcomes in the eyes reviewed in this natural history study as compared with those that have been treated with photocoagulation should not be unexpected, because there is greater predilection for spontaneous involution or autoinfarction of the neovascular tissue in SC disease as opposed to the neovascularization that develops in other retinal vascular disease. A controlled, multicenter clinical trial designed to study those eyes at greatest risk should be considered. Such a trial should specify patient age (15 to 30 years), hemoglobin type (SC disease), and a minimum threshold of active proliferative disease (60 degrees or greater). Such criteria have been suggested by others. By comparing the outcome of eligible eyes randomly assigned to treatment or observation and followed for an extended period, it will be possible to learn whether laser photocoagulation offers a better prognosis than the natural history of proliferative sickle retinopathy. There is no question that in some eyes with proliferative sickle retinopathy, nonclearing vitreous hemorrhage and/or retinal detachment will develop. Clear definition of the risk factors leading to these advanced stages, however, is lacking, and the value of treatment is uncertain. PMID- 1494833 TI - Experimental postoperative endophthalmitis. AB - Various inocula of vancomycin-sensitive E faecalis (EF01), S aureus (SA02), S epidermidis (SE03), and B cereus (BC04), were intravitreally inoculated into an aphakic rabbit model with and without vancomycin, with or without vitrectomy. A summation average of the clinical response mean scores of various inocula (10(3), 10(5), 10(7) cfu) in the absence of therapy ranked these etiologic agents in the order of severity as SE03 (1.4), BC04 (1.8), EF01 (2.3), and SA02 (2.8). These favorably compared with the histopathology cavitary/noncavitary mean scores in increasing order of severity: SE03 (1.7/0.6), BC04 (1.7/0.9), EF01 (2.4/1.1), and SA02 (2.5/1.5), compared with control eyes (1.1/0.4). If the inoculum was increased to 10(7) cfu, SE03 (2.4/0.9) and BC04 (2.8/2.0) could equate EF01 and SA02. Treatment with 1 mg of vancomycin, with or without vitrectomy, did not significantly alter the overall inflammatory response to these four endophthalmitis isolates. No treatment was necessary to achieve > 99.9% killing effect by 72 hours when testing BC04, while any of the treatment modalities during 72 hours achieved 99.9% killing effect when testing SE03. No treatment modality achieved a 99.9% killing effect when testing EF01 or SA02. No single in vitro result could predict the in vivo microbiologic behavior of this model. Further research is needed to better understand the role of antiinflammatory agents, multiple drug therapy, and multiple-injection single-drug therapy with or without vitrectomy, and their impact on the inflammatory response in the aphakic model, to better treat endophthalmitis and thus improve visual prognosis. PMID- 1494834 TI - Retinopathy in a population-based study. PMID- 1494831 TI - Linkage analysis of Norrie disease with X-chromosomal ornithine aminotransferase. PMID- 1494838 TI - Transamerica occidental executive address. PMID- 1494837 TI - State of the association address. PMID- 1494839 TI - Principles of insurance and actuarial science. PMID- 1494840 TI - Medical Information Bureau report. PMID- 1494841 TI - The Academy of Life Underwriting. PMID- 1494836 TI - Occult glove perforation during ophthalmic surgery. AB - We examined the latex surgical gloves used by 56 primary surgeons in 454 ophthalmic surgical procedures performed over a 7-month period. Of five techniques used to detect pinholes, air inflation with water submersion and compression was found to be the most sensitive, yielding a 6.80% prevalence in control glove pairs and a 21.8% prevalence in postoperative study glove pairs, for a 15.0% incidence of surgically induced perforations (P = 0.000459). The lowest postoperative perforation rate was 11.4% for cataract and intraocular lens surgery, and the highest was 41.7% for oculoplastic procedures. Factors that correlated significantly with the presence of glove perforations as determined by multiple logistic regression analysis were oculoplastic and pediatric ophthalmology and strabismus surgical procedures, surgeon's status as a fellow in training, operating time, and glove size. The thumb and index finger of the nondominant hand contained the largest numbers of pinholes. These data suggest strategies for reducing the risk of cross-infection during ophthalmic surgery. PMID- 1494842 TI - Risk selection in the 1990s. PMID- 1494843 TI - Long-term care underwriting. PMID- 1494844 TI - The current status of liver transplantation. PMID- 1494835 TI - Laser photocoagulation for corneal stromal vascularization. PMID- 1494845 TI - Lung transplantation. PMID- 1494846 TI - Comments on economic issues impacting organ transplantation. PMID- 1494847 TI - Donor organ shortage. PMID- 1494848 TI - Future directions in transplantation research. PMID- 1494849 TI - Clinical use of tumor markers. PMID- 1494850 TI - Potential for tumor markers as screening tools for early cancer diagnosis. PMID- 1494851 TI - Preliminary experience with tumor markers. PMID- 1494852 TI - Work and retirement: new slant for the 90s. PMID- 1494853 TI - Rehabilitation and insurance relationships. AB - The ultimate goal of the health care process is to restore an individual to a maximal level of function within the constraints of the existing pathology. It is unfortunate, however, that this potential is often underestimated so that the individual is deprived of reintegration in society. Rehabilitation is the unfinished business of medicine. Reasonable goals need to be identified and clear cost benefit projections need to be established regarding any intervention. To decrease an individual's dependency means that the lifetime cost of care of the individual decreases dramatically. Physical independence and cognitive competency reestablish for the patient optimal levels of health care that need to be facilitated, and involve integrated, innovative insurance liaisons to assure achieving this goal. PMID- 1494854 TI - Health access America: the growing ferment. PMID- 1494855 TI - The status and treatment of rheumatic disease and its impact on mortality. PMID- 1494856 TI - Reference interval and critical difference for canine serum fructosamine concentration. AB - The purposes of the study were to obtain a reference interval and to calculate the critical difference between two analytical results for canine serum fructosamine concentration. To obtain a reference interval, the serum fructosamine concentration was measured in blood samples from 29 adult dogs after a 15-h fasting period. To calculate the critical difference, blood samples from 20 apparently clinically healthy dogs were collected once weekly for five consecutive weeks, and the total variance of the analytical results was divided into the component of variance between dogs (S2inter), the component of variance for weeks within dogs (S2intra) and the component of variance for measurements (S2anal), using nested analysis of variance. The critical difference was then calculated from S2intra and S2anal. The main conclusions are in summary: The reference interval for canine serum fructosamine concentration is 258.6-343.8 mumol/L, and the critical difference between two consecutive measurements on a week-to-week basis is 32.4 mumol/L. The critical difference may be used as a guideline to indicate potentially important changes in the serum fructosamine concentration, though the analytical results should not be assessed by the critical differences alone, but should also be compared to the corresponding reference intervals. PMID- 1494857 TI - Gastrointestinal helminths and lungworms of French dairy goats: prevalence and geographical distribution in Poitou-Charentes. AB - A study was conducted on 81 dairy-goat farms in western France. Faecal samples were collected once and 31 culled goats were necropsied in order to assess their gastrointestinal and respiratory helminth species, their prevalences and the intensities of infection as well as their geographical distribution in six subregions of the surveyed area. Fifteen species of helminth were recovered. The most frequent were Muellerius capillaris, Trichostrongylus colubriformis and Teladorsagia circumcincta with a prevalence more than 90%. The two latter species represented respectively 50.9% and 30.2% of the total worm burden of the digestive tract. Other prevalent species were Haemonchus contortus, Strongyloides papillosus, Trichuris spp., Moniezia spp. and Dicrocoelium lanceolatum. The occurrence of Dicrocoelium lanceolatum was related to the presence of calcareous or alkaline soils and restricted to the south of the surveyed area. No area at particular risk was defined for the other helminth infections, probably because of the relative homogeneity in climatic and topographic conditions of the six agricultural regions. PMID- 1494858 TI - Parenchymal injury and biliary obstruction in relation to photosensitization in sporidesmin-intoxicated lambs. AB - The hepatic changes were compared in lambs photosensitized or not photosensitized after exposure to sporidesmin. Injury to both the parenchyma and the biliary system was more severe in the photosensitized than in the non-photosensitized lambs. The activities of gamma-glutamyltransferase and glutamate dehydrogenase, and the total, conjugated and unconjugated bilirubin concentrations were significantly higher in sera from the photosensitized than from the non photosensitized lambs. Hepatic glycogen levels were decreased in both the photosensitized and the non-photosensitized lambs, but were significantly lower in the former. Hence it is possible that lesions in hepatocytes contribute to retention of phylloerythrin and so to photosensitization. PMID- 1494859 TI - The vascular responses of the isolated perfused bovine external ear to exogenous histamine and 5-HT (serotonin). AB - The responses of the vasculature of isolated, non-sensitized, bovine external ears to histamine and serotonin (5-HT) were evaluated while they were being perfused with Krebs-Henseleit solution. Histamine (10(-5) mol/L to 5 x 10(-3) mol/L) and 5-hydroxytryptamine (5-HT) (10(-9) mol/L to 10(-2) mol/L) caused increased vascular resistance. Mepyramine (10(-7) mol/L), cimetidine (10(-5) mol/L) and atropine (10(-6) mol/L) inhibited the responses to histamine. The responses to 5-HT were inhibited by methysergide (10(-9) mol/L) and potentiated by morphine (10(-5) mol/L). These results suggest the presence of H1 and H2 histamine, and 5-HT receptors in bovine auricular vessels, all of which cause net vasoconstriction. PMID- 1494860 TI - The influence of age on the pharmacokinetics of aditoprim in pigs after intravenous and oral administration. AB - Some pharmacokinetic parameters of aditoprim were determined in 3- and 6-month old pigs. After intravenous administration of 5 mg/kg body weight, the mean total body clearance of the older pigs was smaller than that of the younger pigs. This difference was not reflected in the elimination half-life. After oral administration of 5 mg/kg body weight, the mean absorption rate constant was smaller and the mean absorption half-life was longer in the older pigs. The age related changes in the pharmacokinetics of aditoprim were not sufficiently pronounced to suggest the necessity of modifying the oral dosage regimen in pigs of this age range. The favourable pharmacokinetics of aditoprim in pigs (large apparent volume of distribution, long elimination half-life and high bioavailability) may permit introduction of this drug into swine practice, after safety and residue depletion studies. PMID- 1494861 TI - The effect of protein binding on ivermectin uptake by bovine brain microvessel endothelial cells. AB - The effect of albumin binding on ivermectin uptake and transfer across the endothelial component of the blood-brain barrier (BBB) was determined with an in vitro model comprised of bovine brain microvessel endothelial cell (BMEC) monolayers. Cellular uptake of ivermectin was limited in the absence of albumin and 90% inhibited in the presence of 10% albumin. Cell membrane association of ivermectin, as followed by fluorescent probe labelling, was observed only at high (micromolar) concentrations of the drug. Membrane association was about 75% inhibited in the presence of albumin. Similarly, transfer across BMEC monolayers was restricted, equivalent to that of BBB impermeant markers. Unlike the uptake studies, however, albumin had little effect on the transfer of ivermectin across BMEC monolayers. These results support recent in vivo findings on the distribution of ivermectin into the brain and suggest that ivermectin has only a limited affinity for the endothelial component of the normal BBB. PMID- 1494862 TI - Food intake and rumen motility in dwarf goats. Effects of some serotonin receptor agonists and antagonists. AB - The serotonergic regulation of feeding behaviour has not so far been studied in ruminants. Therefore, the effects of some serotonin (5-HT) receptor agonists and antagonists on food intake and forestomach motility were studied in dwarf goats. Goats ate less food when treated intravenously (IV) with the 5-HT precursor 5-HTP (25 micrograms, 50 micrograms or 100 micrograms kg-1 min-1 over 15 min) than when they were treated with 5-HT (which does not pass the blood-brain barrier) or with saline. Accordingly, IV dexfenfluramine infusions (50 micrograms or 100 micrograms kg-1 min-1 over 15 min), which induces release of brain 5-HT, also led to dose-related reductions in food intake. In contrast, no anorectic effects were observed after IV infusions with the selective 5-HT reuptake inhibitor fluoxetine (100 micrograms kg-1 min-1 over 15 min), the selective 5-HT1A agonist 8-OH-DPAT (0.5 micrograms kg-1 min-1 over 15 min), or eltoprazine (4 or 8 micrograms kg-1 min-1 over 15 min), a mixed 5-HT1A/5HT1B receptor agonist. None of the 5-HT antagonists tested gave any increase in food consumption in this model. Interestingly, the non-selective 5-HT receptor antagonist methysergide (360 micrograms/kg IV) reduced food intake. This effect was most noticeable at 3 h after injection. The 5-HT3 receptor antagonist ondansetron (IV 10 micrograms kg-1 min-1 over 15 min) and the peripheral 5-HT2 receptor antagonist xylamidine (IV 100 micrograms kg-1 min-1 over 10 min) failed to modify food intake. These results provide evidence for central serotonergic involvement in the control of feeding. However, this control system differs markedly in goats and rodents. Dexfenfluramine, 5-HTP and eltoprazine administered at similar dose rates to those used in the food intake experiments induced some clinical signs including inhibition of forestomach contractions. These results, together with our earlier in vivo and in vitro observations, suggest that the inhibitory effects of serotonin receptor agonists on forestomach contractions are due to interactions with both peripheral and central serotonergic receptors. The change in smooth muscle tension, which leads to a change in the signals transmitted via vagal afferents to the central nervous system, appears not to modify feeding behaviour in dwarf goats. PMID- 1494864 TI - A modified filter paper technique for serosurveillance of Newcastle disease. PMID- 1494865 TI - [The dilemma of syndrome X]. AB - The term X syndrome involves several dilemmas. The terminological dilemma is that this term is used to describe microvascular angina pectoris, as well as Reaven's metabolic-hormonal syndrome and our 5H syndrome [association of hyperinsulinism with arterial hypertension, hyperlipoproteinaemia, hyperglycaemia (NIDDM) and hirsutism]. It is probable that the coronary X syndrome is frequently conditioned by the hormonal-metabolic X syndrome. The pathogenetic dilemma is that it is not clear why in microvascular angina pectoris the coronary circulation does not possess an adequate reserve for vasodilatation during exercise or in response to some pharmacological stimuli. This could condition hyperinsulinism in hypertonic subjects with NIDDM with an early disorder of paracrine endothelial relaxation mechanisms (EDRF-NO), with a predominance of vasoconstrictor mechanisms (endothelin-1). In Reaven's syndrome X it is not clear whether insulin resistance of the postreceptor type is a primary inborn phenomenon which is compensated by insulin hypersecretion or whether it is a secondary phenomenon, which develops ex post and by which the target tissues defend themselves against an excessive effect of insulin (e.g. down regulation receptors) in primary disorders of its secretion. PMID- 1494863 TI - Technical and methodological requirements for reliable haemodynamic measurements in the unsedated calf. AB - The purpose of this study was (1) to evaluate the technical and methodological problems associated with invasive haemodynamic measurements in unsedated cattle; (2) to assess the reproducibility of such measurements both within and between days; and (3) to compare the values with those previously reported. Twenty-one healthy calves, aged from 5.5 to 12 months, were studied. The central venous, the right ventricular, the pulmonary arterial, the pulmonary capillary wedge and the systemic arterial pressures were obtained by means of fluid-filled catheters, and the cardiac output was measured by the thermodilution technique. The heart rate, the stroke volume, the pulmonary and systemic vascular resistances and the pulmonary and systemic ventricular workloads were calculated. An adverse reaction, consisting of severe pulmonary hypertension, tachycardia, tachypnoea and transient weakness, occurred in 7 calves during the catheterization procedures. Such a reaction might be due to a local reflex induced by stimulation of mechano-receptors by the catheter tip. It should be avoided by reducing the manipulation of the catheter as much as possible and by inflating the tip of the balloon when moving it forwards. A comparison of the vascular pressures with those previously reported was difficult because of methodological or technical limitations, such as, for instance, a lack of standardization of the baseline. The reproducibility of the haemodynamic measurements obtained was satisfactory, in contrast to previous studies performed in conscious animals. This was attributed to our animals being better trained to the experimental conditions and emphasizes the importance of reducing mental stress in obtaining reliable haemodynamic measurements in unsedated and potentially uncooperative animals. PMID- 1494866 TI - [Long-term effect of drug therapy in supraventricular dysrhythmia evaluated by diagnostic esophageal cardiac pacing]. AB - The authors investigated the long-term therapeutic effect in 33 patients after a medicamentous reversal of recent atrial fibrillation and 18 patients after reversal of an attack of supraventricular tachycardia (SVT). None of the patients had signs of cardiac failure. A change to sinus rhythm was achieved in the group with atrial fibrillation by digoxin with verapamil, in the group with SVT by verapamil. Treatment was then adjusted, based on testing by means of diagnostic oesophageal pacing. The basic drug for long-term use in atrial fibrillation was digoxin either as monotherapy or in combination; the majority of patients with SVT had verapamil treatment. At the end of the period 24.5 +/- 8.4 (12-36) months after the reversal in the group with atrial fibrillation 8 (25.8%) had permanent atrial fibrillation or different therapy on account of atrial fibrillation; short term attacks of palpitation were recorded during the investigation period in 16 (51.6%), and the remaining 7 patients (22.6%) had no complaints. In the group with SVT none of the patients was hospitalized on account of persisting dysrhythmia and it was not necessary to alter treatment. Testing treatment of supraventricular dysrhythmias by means of diagnostic oesophageal pacing is of prognostic importance and the authors consider it the method of choice. PMID- 1494867 TI - [Directed sympathetic denervation of the heart--an actual therapeutic method or myth?]. AB - Aimed sympathetic denervation of the heart, i. e. bilateral removal of the stellate ganglion Th 1-Th 3 was used in Czechoslovakia since 1981 in eight patients who were followed up for prolonged periods. The patients were operated on account of angina at rest which caused deterioration of the quality of their lives. In case of extensive affection of the coronary arteries surgical treatment was not feasible and pharmacological treatment did not bring relief. At the time of a five-year check up 7 patients survived. All patients reported relief and their efficiency during ergometry improved. Four of the patients worked for several years. The authors discuss whether the above treatment is still justified. PMID- 1494868 TI - [Hyperinsulinism and the coronary syndrome]. AB - In one third of patients who suffered an infarction NIDDM and arterial hypertension are present. In the absolute majority of patients with IHD, as apparent from the IRI and C-peptide response after a glucose load, hyperinsulinism is present. The blood sugar response can have the character of diabetes or of impaired glucose tolerance, the curve may be very flat or normal while the IRI and C-peptide response are excessive. Hyperinsulinism has a hypersecretory origin as suggested by the concurrently elevated C-peptide level but also reduced insulin utilization in the liver and peripheral target organs. Hyperinsulinism is thus a regular associated phenomenon of IHD and is a special risk factor independent on hyperglycaemia and associates with the other main risk factors of IHD such as arterial hypertension, HPLP (android obesity), hyperglycaemia (NIDDM) and hirsutism as a manifestation of a hyperandrogenic state in the female organism with the syndrome of polycystic ovaries. Hyperinsulinism plays an indirect role in the pathogenesis of coronary syndrome via the main risk factors (5H syndrome--hyperinsulinism, hypertension, HPLP, hyperglycaemia, hirsutism) and also directly by its action on endothelial paracrine mechanism of the coronary circulation where in the early stage vasoconstrictor factors predominate (endothelin-1, PGF2-alpha) over physiological vasodilatating factors (EDRF-NO, PGE2, PGI2) and this leads then to functional spasms. It seems that also the coronary X syndrome develops very frequently on the background of the hormonal metabolic X syndrome or the 5H syndrome. PMID- 1494869 TI - [24-hour effect and tolerance for perindopril (Prestarium) in mild and moderate essential hypertension]. AB - A multicentre investigation of antihypertensive treatment by perindopril was conducted in three centres of Czechoslovakia. The investigation comprised 51 patients with mild to moderate essential hypertension (diastolic pressure 95-115 mmHg) who were taking perindopril for a period of three months, the initial dose being 4 mg (1 tablet per day). If the blood pressure did not drop to normal levels (dBP < 90 mmHg), the dose was increased to 8 mg after 1 month and if after 2 months of treatment the blood pressure did not reach normal levels, a thiazide diuretic was added. The antihypertensive effectiveness was assessed 24 hours after ingestion of the drug. The blood pressure declined significantly already after the first month of monotherapy with perindopril. It declined then significantly up to the end of the 3rd month of treatment. The systolic blood pressure declined by 9.4 mmHg after the first month of monotherapy with perindopril and by 15.9 mmHg after 3 months of treatment. The diastolic blood pressure declined by 8.1 mmHg after one month of monotherapy and by 12.4 mmHg at the end of three-month treatment. The clinical and biological tolerance was excellent and only one patient discontinued treatment for reasons not related to the administered drug. Twenty-four hour monitoring of the blood pressure also proved the favourable effect of perindopril. PMID- 1494870 TI - [Gestational diabetes mellitus and disorders of glucose tolerance in pregnant women with essential hypertension]. AB - The authors revealed during dispensarization of pregnant women suffering from essential hypertension that the disease is relatively frequently associated with some metabolic disorders, i. e. obesity, gestational diabetes or impaired glucose tolerance. They draw attention to a similarity with Reaven's syndrome in non pregnant women. The authors recommend to screen for diabetes all obese pregnant women and those with hypertension to detect an impaired glucose metabolism and prevent foetopathies in neonates of thus affected mothers. The authors consider obesity one of the subsidiary criteria in the differential diagnosis of essential hypertension and preeclampsia. PMID- 1494872 TI - [Prenatal preparation--a part of the care of young female diabetic patients]. AB - In the Second Gynaecological and Obstetric Clinic in Brno there has been for more than 15 years a specialized department for treatment of diabetes during pregnancy. The department monitors and treats pregnant diabetics from approximately two thirds of the former South Moravian region, i.e. patients with diabetes assessed before pregnancy as well as those where an impaired carbohydrate metabolism was detected during pregnancy. The authors submit an account of the organization of team work in their out-patient department. PMID- 1494871 TI - [The effect of self-monitoring on perinatal outcome in insulin therapy of diabetic women during pregnancy]. AB - The authors compare perinatal results in insulin treated diabetic women who were followed up in the out-patient department of the Second Gynaecological and Obstetric Clinic of the Masaryk University in Brno. In 1980-1984 148 pregnant diabetic women were followed up and in 1985-1991 when self-monitoring has become part of comprehensive treatment of pregnant diabetics in our department, 279 women were followed up. The patients were monitored during pregnancy by a diabetologist and gynaecologist. Other members of the team are a paediatrician, geneticist, psychologist, dietitian, and educational nurse. As to laboratory parameters, short-term and long-term compensation of diabetes were monitored. Systematic preconception preparation of diabetic patients, with an attempt to achieve normal blood sugar levels and genetic examination of both partners from part of comprehensive care. The results achieved in our department revealed a statistically significant decline of the incidence of foetopathies in neonates at the 5% level of significance and a decline of hypoglycaemia in foetuses at the 0.1% level. PMID- 1494873 TI - [Ablation of the accessory bundle of Kent using radiofrequency current in a 17 year-old boy with type A Wolff-Parkinson-White syndrome]. AB - The authors describe the in Czechoslovakia so far not used therapeutic catheterization ablation method of the accessory atrioventricular pathway in patients with tachycardia with the Wolff-Parkinson-White syndrome. They performed successful ablation of the accessory bundle of Kent located by electrophysiological examination behind the left atrium and left ventricle in a 17-year-old boy with WPW Syndrome type A. They severed the accessory pathway by radiofrequency current using a catheter inserted from a retrograde approach into the left ventricle beneath the mitral valve. After ablation the boy suffers no longer from tachycardia, the ECG tracing in devoid of preventricular preexcitation, although he has no medicamentous treatment. PMID- 1494874 TI - [Subphrenic abscess--a complication of intensive cytostatic treatment in acute leukemia]. AB - The authors describe the slow development of an abscess in the left subphrenic space in a patient with acute myeloid leukaemia. The patient suffered several months before the diagnosis was established from pain in the left subcostal region and was on account of this pain examined repeatedly by clinical methods and sonography. During the last sonographic examination in this area a hypoechogenic formation was detected. The diagnosis was than established more accurately by computer tomography by visualization of the abscess cavity. The case-history and relatively thick wall of the cavity suggested a long-term process. The abscess cavity was evacuated surgically, however, the patient suffered a relapse later and died from septicaemia. In the discussion the authors analyze the problem of development of metastatic abscesses in leukopenic patients, early diagnosis and treatment. PMID- 1494875 TI - [A new concept of atherogenesis: the role of oxygen radicals]. AB - The author discusses a new concept of atherogenesis which is based on older hypotheses (lipid infiltration hypothesis), theory of impaired endothelial barrier, role of immunological and thrombocytic factors) and supplements it by new findings on the role of oxygen radicals in the development of atherosclerosis. The atherogenity of native low density lipoproteins (LDL) is enhanced substantially by their post-secretory changes caused by the action of free oxygen radicals on unsaturated fatty acids in the outer layer of LDL particles. The development of lipid peroxides on the surface of LDL leads to a changed orientation of the metabolism of LDL particles: oxidized LDL are not bound to classical LDL receptors in the liver but to so-called scavenger receptors in monocytes and macrophages. Lipid accumulation in monocytes, not controlled by feedback mechanisms, leads to formation of foam cells which are the basis of atheromatous plaques. This process can be influenced by antioxidants which block the formation of lipid peroxides. The new concept is particularly important for the population of Czechoslovakia and other formerly totalitarian countries where deterioration of the environment occurred and concurrently also adverse dietary changes (high fat, sucrose and spirit intake, low vegetable and fruit consumption). It is probable that an increased intake of antioxidants (ascorbic acid, carotenes, tocopherols, bioflavonoids, selenium etc.) would, along with other corrective provisions, suppress the steep increase of cardiovascular diseases. PMID- 1494876 TI - [Insulin resistance as a risk factor in atherosclerosis]. AB - Clinical complications of atherosclerosis are the main cause of mortality in the most advanced countries. Epidemiological data supported by extensive perspective investigations suggest the role of hyperinsulinaemia as an independent risk factor in the development of atherosclerosis. The authors summarize the trends in research of insulin resistance, its possible diagnostic and treatment. PMID- 1494877 TI - [Therapy of developed atherosclerosis]. AB - Atherosclerosis is a reversible process and is an excessive response to damage of the vascular wall. It comprises a number of cellular processes and humoral modulations/regulations the pathogenesis of which is intensively studied. The reversibility of atherosclerosis changes fundamentally the approach to its prevention and therapy, and the effectiveness of anti-aggregation and antihyperlipaemic therapy has been proved. Other preventive and therapeutic procedures are intensively studied. PMID- 1494878 TI - [New pathogenic findings on the mechanism of heart failure and their importance in therapy]. AB - Activation of the neuroendocrine system participates in a decisive way in the pathogenesis of cardiac insufficiency. The authors draw attention to the basic therapeutic impact of the phenomenon of so-called "down-regulation" of myocardial beta-adrenoreceptors which takes place during chronic cardiac insufficiency, contrary to acute cardiac failure. The authors deal from the pathogenetic aspect with different groups of positive inotropic substances used in the treatment of cardiac insufficiency with special attention to digoxin and cardiac glycosides. They evaluate the effect of digoxin as a neurohumoral modulator in acute and chronic cardiac insufficiency. Its potential asset is the positive modulation of excessive neuroendocrine activation and the favourable effect on cardiopulmonary baroreflexes. The authors explain also why at present among positive inotropic substances in the treatment of cardiac insufficiency only cardiac glycosides are indicated. They mention the theoretical possibility to extend the indication of digoxin to retard the progressive deterioration of cardiac function in asymptomatic dysfunction of the left ventricle caused by the neurohumoral modulating effect of digoxin. PMID- 1494879 TI - [Pathogenesis and fundamentals of treatment in acute myocardial infarct]. AB - Recent findings which extend and render more accurate factors which influence the genesis and course of experimental and clinical acute myocardial infarction change in a significant way the treatment and management of patients with acute infarction. The authors discuss the basic factors and complex of interactions which play the most important part in the pathophysiology of acute infarction. They pay attention also to other factors which can influence in a significant way the course of acute infarction and the patient's prognosis (residual thrombosis, rethrombosis, extension, expansion of the infarction and remodelling of the left ventricle). In recent years it has become obvious that the most important determinants of the final extent of acute infarction is the duration and site of occlusion of the coronary artery, its recurrence and degree (magnitude), the condition of the collateral circulation and the consumption and requirements of the myocardium with respect to oxygen during the time of occlusion. The contemporary reperfusion-thrombotic era of treatment of acute myocardial infarction and management of the patient is based on logical multifactorial and to a certain extent preventive, active or aggressive approach and omission of all even potentially harmful approaches. All therapeutic operations (incl. invasive and radical ones) must be consistent with contemporary pathogenetic findings. They should be implemented before possible reinfarction, sudden cardiac death or treatment which has only little effect on heart failure which may be associated also with undesirable expansion of the infarction and remodelling of the left ventricle after acute myocardial infarction. Recent pathophysiological findings and the development of treatment of myocardial infarction are a challenge for cardiologists of the nineties to make use of these important findings in the treatment of patients with myocardial infarction and to ensure for them optimal treatment and management. PMID- 1494880 TI - They take nursing one step further. Nurse practitioners focus on prevention, health promotion. PMID- 1494881 TI - 21 years of Xenobiotica. PMID- 1494882 TI - Ester hydrolysis and conjugation reactions in intact skin and skin homogenate, and by liver esterase of rabbits. AB - 1. Procaine, 2-chloroprocaine, ethyl aminobenzoate and methyl salicylate were added at various concentrations to liver esterase, supernatant of skin homogenate, or single-pass perfused ears of rabbits. 2. Vmax of product formation by purified liver esterase correlated with the rank order of the distribution coefficients (n-octanol/buffer) of the substrates and ranged between 11 and 1100 pmol/min per micrograms protein. Km values were between 20 and 50 microM. 3. No correlation was observed when the apparent enzyme kinetics, calculated by non linear adaptation, were compared with each other after substrate administration to skin, arterial influx, or incubation with skin homogenate. 4. An acid labile conjugate of ethyl 4-aminobenzoate was found, mainly during arterial perfusion and in supernatant of skin homogenate, after administration of ethyl 4 aminobenzoate. 5. Acetamidobenzoic acid was observed in quantities of about 10% of the free 4-aminobenzoic acid during dermal or arterial application of procaine. This metabolite was not found with ethyl 4-aminobenzoate. 6. The results from isolated rabbit ear perfusion differ quantitatively and qualitatively with those obtained from supernatant of skin homogenate or purified liver esterase. PMID- 1494884 TI - Biotransformation of tri-substituted methoxyamphetamines by Cunninghamella echinulata. AB - 1. Four trimethoxyamphetamine analogues were incubated with the filamentous fungus Cunninghamella echinulata. 2. 2,4,5-Trimethoxyamphetamine and 2,5 dimethoxy-4-ethoxyamphetamine were poorly metabolized by C. echinulata ATCC 9244 and C. echinulata var. elegans ATCC 9245. 2,5-Dimethoxy-4-(n)-propoxyamphetamine was mainly metabolized through N-acetylation and O-dealkylation with minor amounts of several aliphatic hydroxylation metabolites formed. 2,5-Dimethoxy-4 methylthioamphetamine was extensively metabolized to the corresponding sulphoxide. 3. 2,5-Dimethoxy-4-methylthioamphetamine metabolism was inhibited by ethanol and quinidine. Sparteine did not inhibit the formation of the sulphoxide and may have shunted the substrate through alternate metabolic pathways. 4. Incubation conditions can affect the rate and extent of fungal biotransformation of 2,5-dimethoxy-4-methylthioamphetamine, and influence dextrose utilization, ammonia formation and pH. PMID- 1494883 TI - Metabolism of methapyrilene by Fischer-344 rat and B6C3F1 mouse hepatocytes. AB - 1. Suspension cultures of freshly isolated F344 rat and B6C3F1 mouse hepatocytes were compared for their ability to transform various concentrations of methapyrilene (MP). 2. MP metabolites were isolated and purified by h.p.l.c., and were identified by comparing their chromatographic and mass spectral properties with those of authentic standards. 3. Both rat and mouse hepatocytes transformed MP to tentatively identified 2-thiophenecarboxylic acid (I), and definitively identified mono-N-desmethyl methapyrilene glucuronide (II), methapyrilene glucuronide (III), methapyrilene N-oxide (V), and mono-N-desmethyl methapyrilene (VII). PMID- 1494885 TI - N-benzylimidazole-mediated changes in hepatic drug-metabolizing enzyme activities in Ah-responsive and Ah-non-responsive mice. AB - 1. The inductive effect of N-benzylimidazole (NBI) on hepatic microsomal and cytosolic drug-metabolizing enzyme activities in aryl hydrocarbon (Ah)-responsive C57BL/6N (B6) and Ah-non-responsive DBA/2N (D2) mouse strains was determined and compared with that caused by beta-naphthoflavone (BNF). 2. Relative Ah responsiveness of the two strains was confirmed by measurement of BNF-induced ethoxyresorufin deethylase (EROD) activity and ELISA immunoquantification. BNF markedly induced EROD activity only in the Ah-responsive B6 mouse strain (65-fold increase). 3. NBI (150 mg/kg per day for 3 days) increased cytochrome P450 concentration similarly in both strains (40 and 60% in B6 and D2 strains, respectively). Compared with BNF treatment of the B6 strain, increases in EROD activity following NBI treatment were only minor. In addition, EROD activity increases were greater in the Ah-nonresponsive D2 strain (300%) than in the Ah responsive B6 strain (100%) suggesting the possibility of an induction mechanism different from that of recognized Ah receptor agonists. 4. Induction of UDP glucuronosyltransferase activity (p-nitrophenol acceptor) by BNF was greater in the Ah-responsive B6 strain than in the Ah-non-responsive D2 strain. NBI failed to induce this activity in either strain. 5. Induction of glutathione S transferase activity towards 1-chloro-2,4-dinitrobenzene following NBI treatment occurred to the same extent (25% increase) as that seen following BNF treatment, in the Ah-responsive B6 strain. Neither xenobiotic affected this activity in the Ah-non-responsive D2 strain. 6. Although NBI is a major inducer, possessing Ah like inducing properties in rat, it caused only minor changes in murine drug metabolizing enzymes.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1494886 TI - Rat liver microsomal metabolism of 2-halogenated 4-methylanilines. AB - 1. Rat liver microsomal metabolism of 2-fluoro-, 2-chloro- and 2-bromo-4 methylaniline was investigated using h.p.l.c. Metabolites identified include products from side-chain C-hydroxylation (benzyl alcohols and benzaldehydes) and N-hydroxylation (hydroxylamines and nitroso derivatives). Aromatic ring hydroxylation was not a major reaction pathway. 2. A new type of microsomal metabolite was detected which was identified as a secondary amine, i.e. a halogenated N-(4'-aminobenzyl)-4-methylaniline. 3. In addition to these products azoxy, azo and hydrazo derivatives were formed. 4. Benzyl alcohols and halogenated N-(4'-aminobenzyl)-4-methylanilines were the major microsomal metabolites for all three 2-halogenated 4-methylanilines. 5. Quantification of the metabolite patterns demonstrated an influence of the type of halogen substituent on the rate of microsomal metabolism. The rate of side-chain C hydroxylation increases in the order 2-fluoro-4-methylaniline < 2-chloro-4 methylaniline < 2-bromo-4-methylaniline. 6. The rate of N-hydroxylation increases from 2-bromo-4-methylaniline < 2-fluoro-4-methylaniline < 2-chloro-4 methylaniline. That 2-chloro-4-methylaniline is N-hydroxylated to a larger extent is in accordance with its greater mutagenicity, twice that of 2-bromo-4 methylaniline. PMID- 1494887 TI - Effect of peroxisome proliferators on glutathione-dependent sulphobromophthalein excretion. AB - 1. The effect of pretreatment of rats with the peroxisome proliferator 2,4,5 trichlorophenoxyacetic acid (2,4,5-T) on sulphobromophthalein excretion from the isolated perfused rat liver has been investigated and compared with the effect of clofibrate which is also a peroxisome proliferator. 2. Rats fed 2,4,5-T at a dose of 0.25% in the diet showed a decrease in food intake, compared with controls and clofibrate-fed rats. 3. Treatment with either 2,4,5-T or clofibrate was associated with significant inhibition of the biliary excretion of unchanged, conjugated, and total sulphobromophthalein from perfused rat liver, compared with diet-matched controls. 4. There was a decrease in bile flow in the clofibrate treated group, but not in the 2,4,5-T-treated group. 5. The results of the present study confirm previous studies that have shown an association between peroxisome proliferation treatment and inhibition of glutathione S-transferase mediated sulphobromophthalein excretion. PMID- 1494888 TI - Modulation of sulphobromophthalein excretion by ethacrynic acid. AB - 1. Ethacrynic acid (EA), a phenoxyacetic acid diuretic, has similar effects to tienilic acid (TA) on rat liver glutathione S-transferase (GST) activity in vitro, using either 1-chloro-2,4-dinitrobenzene or sulphobromophthalein (BSP) as a substrate. EA inhibits the basic rat liver GST, with inhibition being greater with GST containing subunits 3 and 4 than with those containing subunits 1 and 2. 2. In vitro inhibitors of GST can inhibit biliary excretion of BSP in a perfused liver. 3. A single bolus dose of EA had no effect on BSP excretion from the isolated perfused rat liver, and this is most likely due to the rapid disappearance of EA from the perfusion media. Experiments using perfused rat liver indicated that a sustained high concentration of EA in the perfusion media has an inhibitory effect on the excretion of both unchanged and conjugated BSP. 4. A decrease in BSP excretion may not be an indicator of liver damage, but a consequence of GST inhibition. PMID- 1494889 TI - Induction of rat hepatic mixed-function oxidases by acetone and other physiological ketones: their role in diabetes-induced changes in cytochrome P450 proteins. AB - 1. To evaluate the role of ketone bodies in diabetes-induced changes in hepatic cytochrome P450 composition, rats were treated with acetone, 3-hydroxybutyrate or 1,3-butanediol. 2. Treatment with acetone enhanced the rat hepatic O dealkylations of ethoxyresorufin and methoxyresorufin, and the hydroxylation of p nitrophenol, but had no effect on lauric acid hydroxylation and ethylmorphine N demethylation. Neither 3-hydroxybutyrate nor 1,3-butanediol modulated the metabolism of the above substrates. 3. Immunoblot analysis of hepatic microsomal proteins revealed that treatment with acetone increased the apoprotein levels of P4501A2, P4502B1/2 and P4502E1. 4. It is concluded that acetone is responsible, at least partly, for the diabetes-induced increase in hepatic microsomal P4501A2, P4502B1/2 and P4502E1 proteins but does not mediate the increases in the P4503A1 and P4504A1 proteins. On the basis of work from our own and other laboratories a mechanism for the diabetes-induced changes in hepatic cytochrome P450 proteins is proposed. PMID- 1494890 TI - Xenobiotic-metabolizing enzyme activities in hybrid cell lines established by fusion of primary rat liver parenchymal cells with hepatoma cells. AB - 1. The activities of xenobiotic-metabolizing enzymes were determined in hybrid cell lines (hepatocytoma, HPCT) which have been established by fusion of liver parenchymal cells from adult rat (PC) with cells from a Reuber hepatoma cell line (FAO). 2. Cytochrome P450 was not measurable spectrophotometrically in FAO and HPCT. P450-dependent conversion of testosterone was below the detection limit in FAO and only marginally present in HPCT. 3. Microsomal and cytosolic epoxide hydrolase, glutathione S-transferase and phenol sulphotranserase were low or even below detection limit in FAO. These enzyme activities were significantly higher in HPCT and correspond to about 1-10% the activities measured in PC. 4. 1 Naphthol UPD-glucuronosyl transferase activity was about 20% in FAO and about 100% in HPCT compared to PC. 5. Metabolic conversion of benzo[a]pyrene was low in FAO, high in PC, and intermediate in HPCT. The presented data, however, do not allow the conclusion whether this intermediate rate is catalyzed by similar P450 isoenzymes as in PC. 6. Due to the easily measurable phase II-metabolizing enzyme activities HPCT may, however, be useful for in vitro enzyme induction or repression studies. PMID- 1494891 TI - Identification of urinary metabolites of human subjects acutely poisoned by p chloronitrobenzene. AB - 1. Urinary metabolites from human subjects acutely poisoned with p-chloro nitrobenzene (p-CNB) were identified by g.l.c.-mass spectrometry. 2. Eight substances, namely, a very large amount of N-acetyl-S-(4-nitrophenyl)-L-cysteine, relatively large quantities of p-chloroaniline, 2-chloro-5-nitrophenol and p chloroformanilide produced by pyrolysis of a substance originating from p-CNB, small amounts of 2-amino-5-chlorophenol and 2,4-dichloroaniline, and traces of p chloroacetanilide and 4-chloro-2-hydroxyacetanilide, were detected in urine samples. 3. All of the absorbed p-CNB was metabolized prior to excretion, as the parent compound was not found in urine. 4. N-Acetylated metabolites of p chloroaniline and 2-amino-5-chlorophenol, resulting from p-CNB by metabolism, were found in only one of eight individuals indicating that this pathway is weak or may be absent in some humans. 5. A scheme for the pattern of metabolic pathways of p-CNB is proposed, and chlorination was considered to be a possible novel metabolic pathway. PMID- 1494892 TI - Can humanities be taught? PMID- 1494893 TI - Should humanities be taught? PMID- 1494894 TI - Patienthood. AB - The experience of being a patient is valuable in learning how to become a humane physician. The behavior of students and house officers is modeled on their attending and senior residents. Interactions with patients will be more likely to resemble the example of senior physicians than any theoretical or ideal example, no matter how well taught. PMID- 1494895 TI - The iliac passion. AB - "The Iliac Passion" traces a return from the new but busy and rapidly growing discipline of "bioethics" to its source in "fundamental philosophical inquiry." The dilemma between bioethics and medicine is examined in two ways. First, the philosophical concept of the "big question" is presented. If we ask of life or of human experience "What does it all mean?", the "it" needs to be defined, and what I propose to do is to "take on" the "it." In Part Two, the task of combining the medical-technical objectifying mode of thinking about patients, necessary to treat them effectively, with the ability to understand and sympathize with their pain and distress, is illustrated by means of a personal story or parable. PMID- 1494896 TI - Restoring the patient's voice: the case of Gilda Radner. AB - In the past few years, the medical case report has been studied as a document that evidences the way the patient and, by extension, the experiential and subjective aspects of an illness tend to be marginalized in contemporary medical theory and practice. First-person narratives about illness, our popular "pathographies," may in part represent our attempt as a culture to respond to this problem of "the vanishing patient." A rich source of information about patient experience, pathographies can be useful to us in locating specific issues in the medical enterprise that need understanding and perhaps require correction. Gilda Radner's It's Always Something demonstrates how two important issues--both neglected in the conventional medical history--powerfully affect the medical enterprise: the hopes, expectations, and wishes of the experiencing patient, and the perceived attitudes and demeanor of the patient's physicians. The restoration of patient and physician to the "history" is important not only because it reminds us of the personal dimension of the medical enterprise, but also because it alerts us to problems of attitude and action that bear directly on diagnosis, course of treatment, and the therapeutic transaction. PMID- 1494897 TI - Humanities and medicine (a slightly dissident view). AB - Programs for humanities and medicine are growing in a number of medical schools in the U.S.A. Proponents of the programs, which are intended to bring together humanists, scientists, physicians, and others, believe that broadening the background of physicians will put a more human face on the practice of medicine, despite its increasingly technological nature. There is little to support this premise, and its successes and failures are not measurable. There are reasons to support the programs, however, but they have more to do with what physicians like and want to do than with what is therapeutic for them. PMID- 1494898 TI - Extracellular intermediates of glucose metabolism: fluxes of endogenous lactate and alanine through extracellular pools in embryonic sympathetic ganglia. AB - The flux rates of lactate and alanine in and out of the cells of an intact tissue, which cannot be measured directly because some of the released materials are reabsorbed, were determined by computer analysis of uptakes and outputs by the whole tissue in the presence of various concentrations of these substances. The outputs of labeled lactate and alanine from [U-14C]glucose and the uptakes of [U-14C]lactate and [U-14C]alanine were measured on intact sympathetic ganglia excised from 15-day-old chicken embryos. The volume and time constant of the extracellular space were measured using labeled lactate, alanine, and sucrose. Models, which mathematically described the cellular uptakes and outputs as functions of the extracellular concentrations, were used to predict the exchanges that would be observed on the whole tissue, and their parameters were adjusted for best fit to the actual observations. The fitted models were then used to calculate the fluxes in and out of the cells and the concentrations in the extracellular space. The following results were obtained: (1) Cellular uptakes of lactate and alanine were both well described by familiar Michaelis-Menten kinetics. (2) The cellular output of [14C]-lactate from [14C]glucose declined with increase in the extracellular lactate concentration, whereas the cellular output of [14C]alanine from [14C]glucose rose with the extracellular alanine concentration. (3) Half-saturation values for cellular uptake, determined from the fitted equations, were 0.45 mM for lactate and 1.17 mM for alanine, both several-fold lower than less relevant estimates for the whole tissue made directly from the uptake observations. (4) As much as 45% of the carbon in the glucose consumed was released into the extracellular space as lactate and alanine, but much of this was reabsorbed. Implications for brain metabolism are discussed. PMID- 1494899 TI - Cerebral cortex ammonia and glutamine metabolism during liver insufficiency induced hyperammonemia in the rat. AB - Hyperammonemia has been suggested to induce enhanced cerebral cortex ammonia uptake, subsequent glutamine synthesis and accumulation, and finally net glutamine release into the blood stream, but this has never been confirmed in liver insufficiency models. Therefore, cerebral cortex ammonia- and glutamine related metabolism was studied during liver insufficiency-induced hyperammonemia by measuring plasma flow and venous-arterial concentration differences of ammonia and amino acids across the cerebral cortex (enabling estimation of net metabolite exchange), 1 day after portacaval shunting and 2, 4, and 6 h after hepatic artery ligation (or in controls). The intra-organ effects were investigated by measuring cerebral cortex tissue ammonia and amino acids 6 h after liver ischemia induction or in controls. Arterial ammonia and glutamine increased in portacaval-shunted rats versus controls, and further increased during liver ischemia. Cerebral cortex net ammonia uptake, observed in portacaval-shunted rats, increased progressively during liver ischemia, but net glutamine release was only observed after 6 h of liver ischemia. Cerebral cortex tissue glutamine, gamma-aminobutyric acid, most other amino acids, and ammonia levels were increased during liver ischemia. Glutamate was equally decreased in portacaval-shunted and liver ischemia rats. The observed net cerebral cortex ammonia uptake, cerebral cortex tissue ammonia and glutamine accumulation, and finally glutamine release into the blood suggest that the rat cerebral cortex initially contributes to net ammonia removal from the blood during liver insufficiency-induced hyperammonemia by augmenting tissue glutamine and ammonia pools, and later by net glutamine release into the blood. The changes in cerebral cortex glutamate and gamma-aminobutyric acid could be related to altered ammonia metabolism. PMID- 1494901 TI - Unsaturated fatty acids esterified in 2-acyl-l-lysophosphatidylcholine bound to albumin are more efficiently taken up by the young rat brain than the unesterified form. AB - The aim of the present study was to investigate whether unsaturated 2-acyl lysophosphatidylcholine bound to plasma albumin is a relevant delivery form of unsaturated fatty acids to the developing brain. Twenty-day-old rats were perfused for 30 s with labeled palmitic, oleic, linoleic, and arachidonic acids in either their unesterified form or esterified in 2-acyl-lysophosphatidylcholine labeled on the choline and fatty acid moieties. Both forms were bound to albumin. Incorporation in brain lipid classes was followed within 1 h. The brain uptake of the unesterified fatty acids reached a plateau at 5-15 min and was maximal for arachidonic acid (0.45% of the perfused dose). The brain uptake of palmitoyl lysophosphatidylcholine was similar to that of palmitic acid, whereas that of other lysophosphatidylcholines increased with the degree of unsaturation (rate and maximal uptake) and was six- to 10-fold higher than that of the corresponding unesterified fatty acid. 2-Acyl-lysophosphatidylcholines were taken up without prior hydrolysis and reacylated into doubly labeled phosphatidylcholine, which was the most labeled lipid class, whereas lipid distribution of the unesterified fatty acid was more diversified. Partial hydrolysis of 2-acyl lysophosphatidylcholine occurred in the brain tissue, and redistribution of the fatty acyl moiety into other phospholipid classes was also observed and was the highest for arachidonic acid. In this case, the percentage of esterification of this fatty acid in phosphatidylinositol (expressed as a percentage of the total lipid fraction) was relatively lower than that observed when the unesterified form was used.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1494900 TI - Is the vulnerability of neurons in the substantia nigra of patients with Parkinson's disease related to their neuromelanin content? AB - The contribution of neuromelanin (NM) to the pathogenesis of Parkinson's disease (PD) has long been suspected. In particular, a correlation has been reported between the estimated cell loss in the mesencephalic dopaminergic cell groups and the percentage of NM-pigmented neurons in these cell groups. To test whether the amount of pigment per cell is a critical factor or whether the presence of NM within a neuron is sufficient to account for the degeneration of dopaminergic neurons, the NM content was measured in each neuron from representative sections throughout the ventral mesencephalon of four controls subjects and four patients with PD. Intraneuronal NM was quantified by a densitometric method, using known amounts of synthetic melanin as standards. In control brains, the distribution of melanized neurons in the nigral complex showed a high proportion of lightly melanized neurons in the ventral tegmental area and the pars alpha and gamma of the substantia nigra (SN), whereas heavily melanized neurons were mostly located in the pars beta and lateralis of the SN. An inverse relationship was observed between the percentage of surviving neurons in PD compared with controls and the amount of NM they contain, suggesting that the vulnerability of the dopaminergic neurons is related to their NM content. Factors other than NM may be involved in the differential vulnerability of catecholaminergic neurons in PD. In particular, the constant topography of the cell loss suggests that cell position within the nigral complex is a key factor. PMID- 1494902 TI - A novel correlation between the levels of beta-amyloid protein precursor and tau transcripts in the aged human brain. AB - beta-Amyloid protein precursor (APP) and tau are implicated in the pathogenesis of Alzheimer's disease. We quantified the levels of APP and tau transcripts in the three cortical regions of 38 aged human brains obtained from consecutive autopsied patients. The level of APP mRNA was directly proportional to that of tau mRNA to a remarkable extent, suggesting coordinate expression of the APP and tau genes, whereas much weaker correlations were noted among mRNAs encoding other neuronal proteins. From the previous data on the differential expression of APP and tau mRNAs, the levels of APP-751 and -695 mRNAs were calculated and found to be proportional to those of four-repeat and three-repeat tau mRNAs, respectively, whereas that of APP-770 mRNA was rather constant. These results suggest that the mRNA concentrations of APP isoforms are linked to those of tau isoforms in the aged human brain. PMID- 1494903 TI - Chronic administration of lithium or other antidepressants increases levels of DARPP-32 in rat frontal cortex. AB - We studied the chronic actions of lithium on rat brain by investigating its effects on cyclic AMP-dependent protein phosphorylation by use of a back phosphorylation procedure. We identified one heavily regulated phosphoprotein in frontal cortex as the 32-kDa dopamine- and cyclic AMP-regulated phosphoprotein (DARPP-32). Immunoblot experiments demonstrated that chronic lithium regulation of DARPP-32 back-phosphorylation is associated with equivalent increases in levels of DARPP-32 immunoreactivity. Lithium regulation of DARPP-32 immunoreactivity required chronic drug administration and was not observed in several other brain regions examined. Moreover, chronic administration of the antidepressant imipramine or tranylcypromine produced a similar increase in levels of DARPP-32 in frontal cortex, whereas other types of psychotropic drugs, including haloperidol, morphine, and cocaine, did not influence DARPP-32 levels. Increased levels of DARPP-32 could reflect a common functional effect on frontal cortex of long-term exposure to lithium and some other antidepressant medications, an effect possibly related to the clinical actions of these drugs. PMID- 1494904 TI - Iron-melanin complex in substantia nigra of parkinsonian brains: an x-ray microanalysis. AB - Using energy-dispersive x-ray analysis on an electron microscope working in the scanning transmission electron microscopy mode equipped with a microanalysis system, we studied the subcellular distribution of trace elements in neuromelanin containing neurons of the substantia nigra zona compacta (SNZC) of three cases of idiopathic Parkinson's disease (PD) [one with Alzheimer's disease (AD)] and of three controls, in Lewy bodies of SNZC, and in synthetic dopamine-melanin chemically charged or uncharged with Fe. Weak but significant Fe peaks similar to those of a synthetic melanin-Fe3+ complex were seen only in intraneuronal highly electron-dense neuromelanin granules of SNZC cells of PD brains, with the highest levels in a case of PD plus AD, whereas a synthetic melanin-Fe2+ complex showed much lower iron peaks, indicating that neuromelanin has higher affinity for Fe3+ than for Fe2+. No detectable Fe was seen in nonmelanized cytoplasm of SNZC neurons and in the adjacent neuropil in both PD and controls, in Lewy bodies in SNZC neurons in PD, and in synthetic dopamine-melanin uncharged with iron. These findings, demonstrating for the first time a neuromelanin-iron complex in dopaminergic SNZC neurons in PD, support the assumption that an iron-melanin interaction contributes significantly to dopaminergic neurodegeneration in PD and PD plus AD. PMID- 1494905 TI - Gene expression of aromatic L-amino acid decarboxylase in cultured rat glial cells. AB - Northern blot hybridization was performed to detect aromatic L-amino acid decarboxylase (AADC) mRNA in primary cultures of astrocytes and C6 glioma cells. The cDNA probe for rat AADC was generated by reverse transcription from rat adrenal gland total RNA and was amplified by the polymerase chain reaction method. AADC mRNA from cultured astrocytes and C6 glioma cells was present as a single band, 2.2 kbp in size, that comigrated with the RNA from rat kidney. Western immunoblot showed a single protein band at 52 kDa for AADC enzyme protein. These findings demonstrate that AADC is expressed in rat glial cells. PMID- 1494906 TI - Quantitation of rat dopamine transporter mRNA: effects of cocaine treatment and withdrawal. AB - Dopamine transporter mRNA levels in the rat substantia nigra were quantified using a sensitive nuclease protection assay with a highly homologous human dopamine transporter cDNA clone. The same probe was also used to visualize dopamine transporter mRNA in the substantia nigra by in situ hybridization. Repeated cocaine administration (15 mg/kg, twice a day for 6.5 days) resulted in a greater than 40% decrease in nigral dopamine transporter mRNA levels. In contrast, dopamine transporter mRNA levels were unchanged after either acute treatment (4 h before death) or repeated cocaine treatment followed by a 72-h withdrawal period. Thus, blockade of the dopamine transporter by repeated cocaine administration may result in the down-regulation of dopamine transporter gene expression in dopamine neurons. PMID- 1494907 TI - Interleukin 1 and tumor necrosis factor-alpha stimulate the production of colony stimulating factor 1 by murine astrocytes. AB - Astrocytes have the ability to secrete colony-stimulating factor 1 (CSF-1), a growth factor known to stimulate the proliferation of brain macrophages. We have studied the effect of cytokines such as interleukin 1 (IL-1), tumor necrosis factor-alpha (TNF alpha), and interleukin 6 (IL-6) on the production of CSF-1 by cultured primary astrocytes and an astrocytic cell line derived from embryonic mouse brain. We observed that both TNF alpha and IL-1 increased CSF-1 mRNA and protein levels in the astrocytic cultures. In contrast, IL-6 was ineffective. The CSF-1 mRNA levels were strongly reduced by incubating immortalized astrocytic cells with staurosporine, a protein kinase C inhibitor, both in the absence and in the presence of cytokines. Conversely, 12-O-tetradecanoylphorbol 13-acetate, a protein kinase C activator, increased CSF-1 mRNA levels. These results suggest a mechanism whereby mononuclear phagocytes could favor their own recruitment in the CNS by producing cytokines. PMID- 1494908 TI - Homeostatic role for gamma-aminobutyric acid in the brain. PMID- 1494909 TI - Genetic aspects of dopamine receptor binding in the mouse and rat brain: an overview. PMID- 1494910 TI - Characterization of soluble neural cell adhesion molecule in rat brain, CSF, and plasma. AB - The polypeptide composition and glycosylation of soluble isoforms of neural cell adhesion molecule (NCAM) in developing rat brain, CSF, and plasma were characterized. Soluble NCAM in rat brain consisted of several glycosylated isoforms. The degree of glycosylation was developmentally regulated. After desialylation, four polypeptides of M(r) values of approximately 190,000 (s1), 135,000 (s2), 115,000 (s3), and 110,000 (s4) were observed. Polypeptides s1, s2, and s3 were also present in CSF, whereas only s3 and s4 were observed in plasma. Treatment of soluble brain NCAM with N-glycosidase F, which removes N-linked carbohydrates, produced polypeptides of M(r) values of approximately 190,000, 125,000, and 108,000-97,000. The monoclonal antibody OB11, which recognizes an epitope on the cytoplasmic part of transmembrane forms of NCAM, did not react with any of the soluble isoforms. Purified soluble NCAM, consisting mainly of s3, contained an N-terminal sequence identical to that of membrane-associated NCAM. Gel filtration of s3 indicated that it was present as a dimer under the chosen conditions. NCAM-expressing glioma cells adhered specifically to immobilized soluble NCAM. This implies that functionally significant soluble forms of NCAM are present in the extracellular fluid. PMID- 1494912 TI - Determination of regional rates of cerebral protein synthesis adjusted for regional differences in recycling of leucine derived from protein degradation into the precursor pool in conscious adult rats. AB - The quantitative autoradiographic L-[1-14C]leucine method for the determination of regional rates of cerebral protein synthesis in vivo takes into account recycling of unlabeled leucine derived from protein degradation into the precursor pool for protein synthesis. We have evaluated the degree of recycling by measuring the ratio of the apparent steady-state leucine specific activity in the precursor amino acid pool (tRNA-bound leucine) to that in the arterial plasma. In the whole brain of the conscious rat this ratio (lambda WB) equals 0.58. The equivalent ratio for leucine in the acid-soluble pool in whole brain (psi WB) is 0.49. A first-degree polynomial equation for lambda WB as a function of psi WB was fitted from paired determinations. To determine the degree of recycling in local regions of the brain, we have measured in individual brain regions (i) psi i and calculated lambda i assuming that the fitted equation also applies to these localized regions. Our results indicate that the degree of recycling into the precursor pool does vary regionally; lambda i in the individual regions varies from 0.62 in the hypoglossal nucleus to 0.50 in the globus pallidus. Local rates of protein synthesis were then determined by the autoradiographic technique with regional corrections for recycling of unlabeled leucine. Rates of leucine incorporation into protein averaged 6.1 nmol/g of tissue/min in the brain as a whole, with the rates in gray matter about twice those in white matter. PMID- 1494911 TI - Characterization of nicotinic receptor-mediated [3H]dopamine release from synaptosomes prepared from mouse striatum. AB - This study establishes that presynaptic nicotinic receptors modulate dopamine release in the mouse striatum. Nicotinic agonists elicit a dose-dependent increase in the release of [3H]dopamine from synaptosomes prepared from mouse striatum. At low concentrations, this release is Ca2+ dependent, whereas at higher concentrations Ca(2+)-independent, mecamylamine-insensitive release was also observed. The Ca(2+)-dependent nicotine-evoked release was not blocked by alpha-bungarotoxin but was effectively blocked by neuronal bungarotoxin as well as several other nicotinic receptor antagonists. The relationship between potency for stimulation of release for agonists and potency for inhibition of release for antagonists was compared to the affinity of these compounds for the [3H]nicotine binding site. The overall correlation between release and binding potency was not high, but the drugs may be classified into separate groups, each of which has a high correlation with binding. This finding suggests either that more than one nicotinic receptor regulates dopamine release or that not all agonists interact with the same receptor in an identical fashion. PMID- 1494913 TI - Cleavage of bovine brain microtubule-associated protein-2 by human immunodeficiency virus proteinase. AB - The high-molecular-weight dendritic cytoskeletal protein known as microtubule associated protein (MAP)-2 displays the capacity to stimulate tubulin polymerization and to associate with microtubules. Serine proteases cleave MAP-2 into a C-terminal M(r) 28,000-35,000 microtubule-binding fragment and a larger N terminal M(r) 240,000 projection-arm region. We now show that human immunodeficiency virus (HIV) proteinase also progressively degrades purified MAP 2 in vitro. This proteolysis reaction is characterized by transient accumulation of at least six intermediates, and most abundant of these is an M(r) 72,000 species that retains the ability to associate with taxol-stabilized microtubules. Treatment of this M(r) 72,000 species with thrombin releases the same M(r) 28,000 component as that derived from thrombin action on intact high-molecular-weight MAP-2, indicating that the viral aspartoproteinase action preferentially occurs further toward the N-terminus. The association of the M(r) 72,000 component with microtubules can be disrupted by the presence of a 21-amino acid peptide analogue of the second repeated sequence in the MAP-2 microtubule-binding region. We also studied HIV proteinase action on MAP-2 in the presence of tubulin and other MAPs that recycle with tubulin, and contrary to other published studies we found no effect of such treatment on microtubule self-assembly behavior. Cleavage of isolated MAP-2 by the HIV enzyme at high salt concentrations, followed by desalting and addition of tubulin, also resulted in microtubule assembly, albeit with slightly reduced efficiency. PMID- 1494914 TI - Endogenous noradrenaline and dopamine in nerve terminals of the hippocampus: differences in levels and release kinetics. AB - The presence and release of endogenous catecholamines in rat and guinea pig hippocampal nerve terminals was studied by fluorimetric HPLC analysis. In isolated nerve terminals (synaptosomes) the levels and breakdown of endogenous catecholamines were determined and the release process was characterized with respect to its kinetics and Ca2+ and ATP dependence. Endogenous noradrenaline and dopamine, but not adrenaline, were detected in isolated hippocampal nerve terminals. For dopamine both the levels and the amounts released were more than 100-fold lower than those for noradrenaline. In suspension, released endogenous catecholamines were rapidly broken down. This could effectively be blocked by monoamine oxidase inhibitors, Ca(2+)-free conditions, and glutathione. The release of both noradrenaline and dopamine was highly Ca2+ and ATP dependent. Marked differences were observed in the kinetics of release between the two catecholamines. Noradrenaline showed an initial burst of release within 10 s after K+ depolarization. The release of noradrenaline was terminated after approximately 3 min of K+ depolarization. In contrast, dopamine release was more gradual, without an initial burst and without clear termination of release within 5 min. It is concluded that both catecholamines are present in nerve terminals in the rat hippocampus and that their release from (isolated) nerve terminals is exocytotic. The characteristics of noradrenaline release show several similarities with those of other classical transmitters, whereas dopamine release characteristics resemble those of neuropeptide release in the hippocampus but not those of dopamine release in other brain areas. It is hypothesized that in the hippocampus dopamine is released from large, dense-cored vesicles, probably colocalized with neuropeptides. PMID- 1494915 TI - Microdetermination of 2-deoxyglucose and 2-deoxyglucose 6-phosphate to determine glucose utilization rates in single neurons and small CNS regions after injecting nontracer amounts of 2-deoxyglucose. AB - A nontracer amount (0.25 mmol/kg of body weight) of 2-deoxyglucose (DG) was intravenously injected into rats, which were frozen 2 and 4 min later in liquid nitrogen. Freeze-dried samples of CNS regions and cell bodies of spinal motor neurons were prepared, and the concentrations of glucose, glucose 6-phosphate, DG, and DG 6-phosphate (DG6P) in them were microassayed after 3,000-1,500,000 fold amplification using an enzymatic amplification reaction, NADP cycling. Based on the time course of glucose, DG, and DG6P concentrations in arterial plasma and the anterior horn of the spinal cord, the Sokoloff-type rate equations for DG and DG6P concentrations were mathematically solved, and the resultant DG and DG6P concentration functions were fitted to the data points using the nonlinear least squares fitting SALS package program. This fitting provided four rate constants for the functions and supported the theoretical basis for our calculations of glucose utilization rate (GUR) when DG was administered in nontracer amounts. The GUR was highest in the spinal motor neurons and lowest in the white matter of the cerebellum. Neuron-rich structures, such as the cerebellar molecular and granular layers and the anterior horn of the spinal cord, had higher GUR values than the white matter of the cerebellum and spinal cord. PMID- 1494916 TI - Effects of hypoxia on choline exchange among organs. AB - Cerebral blood flow (CBF) and the arteriovenous (A-V) difference for choline (Ch) across brain, lung, splanchnic territory, liver, kidney, and lower limb were studied in anesthetized, mechanically ventilated rats subjected to 10-20-min periods of hypoxia induced by lowering the inspired O2 concentration to 13%. A large, time-dependent increase in arterial blood Ch concentration occurred during hypoxia. This phenomenon coincided with a net rate of uptake of Ch by the brain during hypoxia (0.81 +/- 0.24 nmol/min, n = 10; p less than 0.05), which contrasted with a net rate of loss of Ch by this organ during the control period that preceded hypoxia (-0.20 +/- 0.08 nmol/min, n = 10; p less than 0.05). During hypoxia, lungs and splanchnic territory showed negative A-V differences for Ch levels (net Ch loss), whereas brain, liver, kidney, and lower limb showed positive A-V differences for Ch levels (net Ch uptake). Ch output from lungs was already detected at 5 min within the period of hypoxia and reversed rapidly after restoration of normal oxygenation. On the other hand, Ch output from the splanchnic territory became evident only 10 min after commencement of hypoxia and outlasted this experimental condition. It is concluded that extracerebral production of Ch during hypocapnic hypoxia raises the arterial concentration of this molecule and, by reversing the gradient across cerebral capillaries, prevents the cerebral loss of Ch in this condition. PMID- 1494917 TI - Cytokine regulation of nerve growth factor-mediated cholinergic neurotrophic activity synthesized by astrocytes and fibroblasts. AB - The neurotrophic activity of astrocytes and fibroblasts and its regulation by various cytokines were investigated. Astrocyte conditioned medium (ACM) enhanced the survival of neurons and the proliferation of astrocytes in embryonic cortical cultures grown in serum-free defined medium. However, these results were not affected by acidic fibroblast growth factor, interleukin-1 beta (IL-1 beta), tumor necrosis factor-alpha (TNF alpha), and transforming growth factor-beta 1. In contrast, ACM induced choline acetyltransferase expression in septal cholinergic neurons via nerve growth factor (NGF)-dependent and -independent mechanisms. However, neither acidic nor basic fibroblast growth factor is involved in this biological activity in ACM. The cytokines listed above mainly stimulate NGF-mediated cholinergic neurotrophic activity in ACM. A combination of IL-1 beta and TNF alpha significantly enhanced choline acetyltransferase activity in septal neurons co-cultured with astrocytes, and this effect was found to be mediated by NGF produced by activated astrocytes. Effects of astrocytes on GABAergic neurons were also examined. ACM was found to increase glutamate decarboxylase activity in neuronal cultures from septum in the presence of Ara-C. However, the cytokines did not enhance this activity in ACM. Moreover, a combination of IL-1 beta and TNF alpha had no effect on glutamate decarboxylase activity in septal neurons co-cultured with astrocytes. In a final set of experiments, cholinergic neurotrophic activity in skin-derived fibroblast conditioned medium (FCM) was examined. FCM was found to possess biological activity similar to that of ACM on septal neurons grown in serum-free defined medium with Ara-C. The cytokines also enhanced NGF-mediated cholinergic neurotrophic activity in FCM. Astrocytes and fibroblasts were found to possess NGF-type and non-NGF-type cholinergic neurotrophic activity, and various cytokines were found to regulate the NGF-type cholinergic neurotrophic activity in both types of cells. NGF produced by astrocytes and fibroblasts that are activated by cytokines is likely to be important for development and regeneration of NGF-sensitive neurons in the central and peripheral nervous systems. PMID- 1494918 TI - Effect of nitroprusside (nitric oxide) on endogenous dopamine release from rat striatal slices. AB - It is becoming apparent that the synthesis of nitric oxide (NO) from L-arginine not only explains endothelium-dependent vascular relaxation, but is a widespread mechanism for the regulation of cell function and communication. We examined the role of NO on the endogenous dopamine (DA) release from rat striatum. Nitroprusside, in the concentration range of 3-100 microM, induced a dose dependent increase in the endogenous DA release from rat striatal slices. The maximal response was 330% over the baseline release. A higher concentration of nitroprusside (300 microM) produced an inhibitory effect on the spontaneous release of DA. L-Arginine (10 and 100 microM), a substrate in the NO-forming enzyme system, also produced an elevation of DA release. L-Arginine-induced DA release was attenuated by NG-monomethyl-L-arginine, an inhibitor of NO synthase. NADPH (1 microM), a cofactor of NO synthase, enhanced L-arginine-induced DA release. These results suggest a possible involvement of NO in the DA release process in rat striatum. PMID- 1494919 TI - Ouabain-sensitive choline transport system in capillaries isolated from bovine brain. AB - In physiological conditions, there is a net transport of choline from brain to blood, despite the fact that the choline concentration is higher in plasma than in CSF. Because of the blood-brain barrier characteristics, such passage against the concentration gradient takes place necessarily through endothelial cells. To get a better understanding of this phenomenon, [3H]choline uptake properties have been analyzed in capillaries isolated from bovine brain. [3H]Choline uptake was linear with time for up to 1 h. Nonlinear regression analysis of the uptake rates at different substrate concentrations gave the best fit to a system of two components, one of which was saturable (Km = 17.8 +/- 4.8 microM; Vmax = 11.3 +/- 3.4 pmol/min/mg of protein) and the other of which was nonsaturable at concentrations up to 200 microM. The [3H]choline transport was significantly reduced in the absence of sodium and after incubation with 10(-4) M ouabain for 30 min. Ouabain also inhibited choline uptake in purified cerebral endothelial cells, but not in the endothelium isolated from bovine aorta. Accordingly, cerebral endothelial cells were able to concentrate [3H]choline, with this effect being abolished by ouabain, whereas in aortic endothelial cells the [3H]choline intracellular concentration was never higher than that of the incubation medium. These results suggest that the blood-brain barrier endothelium is specifically provided with an energy-dependent choline transport system, which may explain the choline efflux from the brain and the maintenance of a low choline concentration in the cerebral extracellular space. PMID- 1494920 TI - Dihydroxyphenylalanine and dopamine are released from portal vein together with noradrenaline and dihydroxyphenylglycol during nerve stimulation. AB - The overflows of 3,4-dihydroxyphenylalanine, dopamine, noradrenaline, and 3,4 dihydroxyphenylglycol in canine portal vein superfused in vitro were studied before, during, and after depolarization of sympathetic nerve endings. The four compounds were separated from superfusate and from tissue on Sep-Pak C-18 cartridges and quantified by HPLC with electrochemical detection. Physiological and biochemical methods were used to show that the compound released was most probably 3,4-dihydroxyphenylalanine; the identity of the other endogenous compounds has been established previously. Release of 3,4-dihydroxyphenylalanine was calcium and frequency dependent, inhibited by a-m-L-p-tyrosine (an inhibitor of tyrosine hydroxylase) and augmented by 3-hydroxybenzylhydrazine (an inhibitor of aromatic amino acid decarboxylase). The overflows of dopamine, noradrenaline, and 3,4-dihydroxyphenylglycol from the vein were calcium and frequency dependent. It was estimated that under control conditions, approximately 80% of the total 3,4-dihydroxyphenylalanine that was synthesized was directed to catecholamine biosynthesis, approximately 8% overflowed from the vein, and approximately 14% remained unchanged within the tissue. It is concluded that 3,4 dihydroxyphenylalanine and dopamine are released together with noradrenaline and 3,4-dihydroxyphenylglycol from portal vein upon nerve depolarization. PMID- 1494921 TI - Effects of [Sar1]angiotensin II on proenkephalin gene expression and secretion of [Met5]enkephalin in bovine adrenal medullary chromaffin cells. AB - We have studied the effect of [Sar1]angiotensin II [S1-AII; a degradation resistant analogue of angiotensin II (AII) on the release of [Met5]enkephalin (ME) and proenkephalin A (proENK) gene expression. Short-term (15-min to 1-h) stimulation of bovine adrenal medullary chromaffin (BAMC) cells with S1-AII at concentrations from 0.1 to 100 nM had no significant effect on secretion of ME, whereas high concentrations of S1-AII (3 to 100 microM) produced a concentration dependent increase in the concentration of ME in the incubation media. In contrast, long-term (3- to 24-h) stimulation with low concentrations (0.1 nM-1 microM) of S1-AII increased the secretion of ME in a concentration-dependent manner (EC50 = 1 nM). The intracellular level of ME was not changed by long-term treatment with S1-AII (100 nM). In addition to increased ME secretion, long-term (24-h) stimulation with S1-AII increased the expression of proENK mRNA in a concentration-dependent manner (EC50 = 4 nM). Losartan (2-n-butyl-4 chloro-5 hydroxymethyl-1-[(2'-(1 H-tetrazol-5-yl)biphenyl-4-yl)- methyl]imidazole potassium salt, a type 1 AII receptor antagonist) inhibited these effects, whereas PD123319 (50 microM, a type 2 AII receptor antagonist) was inactive. Our results suggest that AII in BAMC cells exerts a major effect on the long-term regulation of expression of proENK mRNA and secretion of ME. These effects appear to be mediated by type 1-like AII receptors. PMID- 1494922 TI - Local blood-brain barrier in the newborn rabbit: postnatal changes in alpha aminoisobutyric acid transfer within medulla, cortex, and selected brain areas. AB - Postnatal changes in local permeability of the blood-brain barrier to an inert neutral amino acid (alpha-[14C]-aminoisobutyric acid) were investigated in 25 rabbits. The local transfer constant (K) for this tracer was measured with quantitative autoradiographic techniques at postnatal ages of 1, 3, 8, and 17 days, and adult. In adults, the amino acid penetrated the blood-brain barrier poorly in most regions examined (K less than 1 microliter.g-1.min-1) except within and in proximity to structures with a relatively leaky blood-brain barrier such as area postrema and choroid plexus. The rate of tracer entry into "impermeable" regions was seven- to 10-fold greater in 1-day-old rabbits than adults and not dependent on active transport. In young animals, there was a pronounced regional variation in K with the lowest values occurring in white matter and the highest in gray matter such as cerebral cortex, posterior thalamus, and hippocampus. During postnatal development, K decreased (p less than 0.01) with most regions having values near those of adults by 17 days of age. The results indicate that the blood-brain barrier of the newborn rabbit is relatively leaky to a small hydrophilic nonelectrolyte with a distribution that is heterogeneous regionally. Irrespective of age, such blood-borne substances can accumulate in certain brain areas considered to have impermeable vessels (e.g., nucleus tractus solitarii). PMID- 1494923 TI - On the shoulders of progress. PMID- 1494925 TI - Can people hear the pitch change on a variable-pitch pulse oximeter? AB - The introduction of the variable-pitch feature on pulse oximeters in 1983 by the Nellcor Corporation (Hayward, CA) allowed users to rapidly detect changes in oxygen saturation by listening for changes in the pitch of the tones emitted by the pulse oximeter. A few individuals have reported that they have been unable to detect a change in pitch when oxygen saturation changes. To these individuals, the variable-pitch feature of these pulse oximeters has not been beneficial. Using the pitches from one manufacturer of oximeters, we created a computer program to simulate the pitches that accompanied various oxygen saturations. The pitches were recorded onto a tape player and played for 75 volunteer subjects unfamiliar with the pitches of a variable-pitch pulse oximeter. Of our sample, 67% were able to detect a single change in pitch corresponding to a 1% fall in oxygen saturation, and 11% of the population could not detect a change in pitch until there was a change in pitch with every beat. We suggested four alternative designs that may prove beneficial to this group of individuals. PMID- 1494924 TI - Radial artery cannulation: a comparison of 15.2- and 4.45-cm catheters. AB - Eighty-nine patients were studied prospectively to compare the incidence of postdecannulation arterial thrombosis and ischemic complications associated with percutaneous insertion of two different radial artery catheters. Patients scheduled for peripheral vascular surgery were randomized to receive a 15.2-cm (6 in, Argon Medical Corp.) or 4.45-cm (1.75 in, Arrow International, Inc.) 20 gauge, Teflon catheter. Extremity blood flow was evaluated prior to cannulation and again after decannulation with the modified Allen's test, pulse-volume plethysmography, and Doppler ultrasound. The incidence of postdecannulation radial artery occlusion for 15.2-cm catheters was significantly less than for 4.45-cm catheters (4 of 45 cases versus 11 of 44 cases, p = 0.05). No case of temporary or permanent ischemic injury occurred. Radial artery transfixion (16 of 45 cases versus 5 of 44 cases, p = 0.01) and hematoma formation (5 of 45 cases versus 0 of 44 cases, p = 0.02) occurred more frequently during insertion of 15.2 cm catheters than 4.45-cm catheters. The number of arterial punctures during catheter insertion and the duration of cannulation were similar for both groups. Of the 8 patients with positive modified Allen's test who underwent radial artery cannulation, one suffered arterial occlusion. Radial artery cannulation with a 15.2-cm catheter was associated with a lower incidence of postdecannulation radial artery thrombosis than cannulation with the 4.45-cm catheter. Radial artery cannulation with longer catheters (greater than 5.0 cm) appears to be a safe practice. PMID- 1494927 TI - Pulmonary artery catheter monitoring during single-lung ventilation in dogs. AB - The effect of pulmonary artery (PA) catheter insertion on cardiac output measurements and the effect of single-lung ventilation on data derived from catheters placed in both the right and left pulmonary arteries were examined in 17 anesthetized mongrel dogs. Serial tricarboncyanine dye measurements of cardiac output were taken at baseline and after insertion of each of two PA catheters, one catheter in each lung, to detect possible changes in cardiac output due to instrumentation. In the second part of the study, single-lung ventilation was achieved through a Kottmeier double-lumen tube. Right and left paired values of thermodilution cardiac output, PA systolic pressure, and PA PO2 were compared during ventilation of both lungs, during right lung ventilation, during return to ventilation of both lungs, and during left lung ventilation. Mean dye-dilution cardiac outputs were not significantly different after one or two catheters were inserted. Paired right and left values were similar for thermodilution cardiac output, PA PO2, and pulmonary systolic pressure, regardless of ventilation conditions. Even during single-lung ventilation, data obtained from PA catheters in the ipsilateral and contralateral lung were equivalent in supine dogs. PMID- 1494926 TI - Educational computer simulation of malignant hyperthermia. AB - An educational graphic simulator was developed to provide an interactive learning environment to practice the diagnosis and treatment of malignant hyperthermia. The program incorporates a set of dynamically interacting models to present the physiologic changes associated with malignant hyperthermia and the simulated patient's response to management. Cardiovascular, respiratory, and temperature changes are presented through a graphic display of the operating room monitors. Mouse-driven input is used to manage the airway, control ventilation, manage cardiovascular and rhythm disturbances, and control fluids, electrolytes, and temperature. Medications, including dantrolene, antidysrhythmics, diuretics, and sodium bicarbonate, can be administered. Four simulated patients with different presentations of malignant hyperthermia are included to illustrate variations in the syndrome. Two of these patients are described in detail. PMID- 1494929 TI - Use of end-tidal PCO2 and transcutaneous PCO2 as noninvasive measurement of arterial PCO2 in extubated patients recovering from general anesthesia. AB - This study was designed to assess the accuracy of end-tidal PCO2 and transcutaneous PCO2 as measurements of arterial PCO2 in extubated, spontaneously breathing patients recovering from general anesthesia. In 30 patients, measurement of arterial transcutaneous, and end-tidal PCO2 were taken simultaneously with body temperature approximately every 15 minutes over a 2-hour period. Arterial PCO2 values were corrected for body temperature. Values for PaCO2 were compared with those for PETCO2 and PsCO2 by linear regression analysis and by calculation of bias +/- precision. Thirty-six percent of the capnogram tracings obtained did not develop a plateau phase. We found poor correlation between end-tidal and arterial PCO2 regardless of the shape of the capnogram tracing, as well as poor correlation between transcutaneous and arterial PCO2. Although the measurements of bias and precision of noninvasive PCO2 monitors in this population are comparable to studies in other populations, we advise caution in relying on the routine use of PETCO2 or PsCO2 for the noninvasive assessment of respiratory depression in extubated, spontaneously breathing patients recovering from general anesthesia. PMID- 1494928 TI - Correlated, simultaneous, multiple-wavelength optical monitoring in vivo of localized cerebrocortical NADH and brain microvessel hemoglobin oxygen saturation. AB - Current forms of brain monitoring, such as electroencephalography (EEG), have had limited clinical utility. The EEG records spontaneous cerebrocortical activity and thus is an indirect indicator of metabolic demand and, to a lesser extent, an indicator of mismatch of supply versus demand. Ischemia modulates EEG activity in ways that can usually be detected, but EEG patterns can be similarly modulated by many other factors, including temperature and pharmacologic manipulation. This in vivo study in physiologically monitored animals evaluated the use of correlated optical spectroscopy, performed with an instrument having a fiberoptic light guide bundle in contact with the cerebral cortex, for the simultaneous monitoring of cerebrovascular oxygen availability and intracellular oxygen delivery. A highly specific monitor of cerebral intracellular oxygen supply, the cerebrocortical intramitochondrial NADH redox state, was monitored in vivo with a fluorescence technique. Absorption spectroscopy was used concurrently to monitor hemoglobin content (blood volume) and oxygen saturation in the microcirculation. Correlated changes in optical signals from cerebrocortical NADH and hemoglobin were studied in a swine model (n = 7) of nitrogen hypoxia. Measurements were made at four wavelengths with a time-division, multiplexed fluorometer/reflectometer. Because the NADH fluorescence signal at 450 nm is affected by local changes in blood volume, a "corrected" fluorescence signal is usually calculated. In previous studies, where only two wave lengths have been measured, attempts at correction were based on reflectance at the excitation wavelength (366 nm). We compared estimators of changes in microcirculatory blood volume using reflection at two wavelengths: 366 nm and 585 nm, the wavelengths for maximum and isobestic absorption. The results of the studies were as follows: (1) during transient hypoxia, NADH and local hemoglobin saturation signals changed in concert with arterial pulse oximetry, with changes in NADH lagging behind changes in saturation by an average of 5.3 seconds; (2) after hypocapnic ventilation to a mean PaCO2 of 20.2 +/- 0.8 mm Hg, NADH increased by 11.5 +/- 8.7% (as compared with maximal change during anoxia), local hemoglobin saturation decreased by 7.7 +/- 6.4%, and local blood volume decreased by 12.5 +/- 13%, while arterial SpO2 was unchanged; (3) our two measures of local blood volume were closely correlated during carbon dioxide perturbations, but poorly correlated during hypoxic perturbation; and (4) NADH fluorescence provided a more rapid, sensitive indicator of oxygen deprivation than did the EEG. During transient hypoxia, EEG changes occurred 57.4 +/- 10.4 seconds after the onset of decline in local hemoglobin saturation, after NADH had completed 50% of its maximal increase. PMID- 1494930 TI - Inconsistencies in the correlation between loss of brain stem auditory evoked response waves and postoperative deafness. AB - This case underscores the difficulty of predicting postoperative hearing status from brain stem auditory evoked response (BAER) monitoring when wave I is preserved and all later waves are lost. During an operation involving the base of the skull, sudden and irreversible loss of all BAER waves beyond wave I occurred unilaterally. Wave I was preserved, with reduced amplitude and minimal latency shift. There was no permanent postoperative hearing sensitivity loss or speech discrimination loss. PMID- 1494931 TI - Capnography does not reliably detect double-lumen endotracheal tube malplacement. AB - Two patients are described in whom double-lumen endotracheal tube malplacement and its ventilatory consequences were not detected by infrared capnography. Problems were suspected on auscultation, and the malplacement was diagnosed by means of bronchospirometry. We conclude that bronchospirometry helps detect problems with endotracheal intubation. PMID- 1494932 TI - STA distinguished lecture. Can technology education during medical school make better doctors? PMID- 1494933 TI - Is portable capnometry useful during transport of the critically ill? PMID- 1494934 TI - A new solution to the problem of maintaining the proper air-fluid level in fluid warmer bubble traps. PMID- 1494935 TI - Continuous monitoring of the flow-volume loops and compliance during anesthesia. PMID- 1494936 TI - Closed-loop control of arterial pressure during cardiac surgery. PMID- 1494937 TI - The role of simulation in the design of control systems. PMID- 1494938 TI - Decline of vasopressin immunoreactivity and mRNA levels in the bed nucleus of the stria terminalis following castration. AB - Vasopressinergic (VP) neurons in the bed nucleus of the stria terminalis (BNST) of the rat are regulated by gonadal steroids. Gonadectomy causes the projections of the BNST to lose their VP immunoreactivity gradually over a period lasting more than 2 months. Here we have compared the rate of decline of VP mRNA and VP immunoreactivity in the BNST of adult male rats following castration. In experiment 1, the peak number of VP-immunoreactive cells and the level of VP gene expression were compared in sham-operated controls and at 1, 3, or 8 weeks postcastration. The number of VP-immunoreactive cells was not decreased at 1 week postcastration but was significantly reduced (p less than 0.0001) at 3 and 8 weeks postcastration. VP gene expression declined more rapidly, and both the total number of labeled cells (p less than 0.0001) and the average number of grains per cell (p less than 0.01) were significantly reduced by 1 week postcastration. No VP-expressing cells were detectable at 3 or 8 weeks. The difference in the rate of decline in the number of cells labeled by the two techniques following castration did not appear to be due to colchicine pretreatment. In experiment 2, VP mRNA in the BNST was compared in sham-operated controls or at 1, 3, or 7 d postcastration. A significant decrease (p less than 0.01) in the average number of grains per cell was detectable by just 1 d following castration, and the number of labeled cells was significantly reduced (p less than 0.001) by 3 d postcastration.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1494939 TI - Synaptic interactions between GABA-immunoreactive profiles and the terminals of functionally defined myelinated nociceptors in the monkey and cat spinal cord. AB - This study analyzes the synaptic interactions between the central terminals of A delta high threshold mechanoreceptors (A delta HTMs) and GABA-immunoreactive profiles. A delta HTM primary afferents from three monkeys and one cat were electrophysiologically identified and intracellularly labeled with HRP, and their terminal arborizations in laminae I and II of the sacrocaudal spinal cord were studied at the ultrastructural level. GABA-immunoreactive profiles in relation to A delta HTM terminals were demonstrated using postembedding colloidal gold techniques. Monkey A delta HTM terminals (n = 131) usually constituted the central element of synaptic glomeruli; they established large asymmetric synaptic contacts with 1-13 dendrites (modal value 2-4) and were surrounded by 0-6 peripheral axon terminals (modal value 2-3). The large majority (around 85%) of the peripheral axon terminals were GABA immunoreactive. They were found presynaptic to the A delta HTM terminal and/or to dendrites postsynaptic to the primary afferent terminal. Furthermore, all peripheral axon terminals found presynaptic to the A delta HTM terminals showed GABA immunoreactivity. Within a single A delta HTM fiber, this synaptic arrangement was found in 20-60% of its boutons. In addition, 28% of the postsynaptic dendritic profiles displayed weak GABA immunoreactivity. Some of them contained vesicles; however, only in a few cases did we observe synapses between a GABA-immunoreactive vesicle-containing dendrite and a dendritic profile postsynaptic to an A delta HTM terminal. Similar synaptology and interactions with GABA-immunoreactive profiles were displayed by the terminals of the single cat A delta HTM fiber studied. Our data support the hypothesis that GABA-containing neurons use both presynaptic and/or postsynaptic mechanisms to exert a powerful control, presumably inhibitory, over the transmission of nociceptive information between A delta HTM afferents and second order neurons in monkey and cat spinal cord. Our results also imply that GABA may be released within the synaptic glomeruli formed by A delta HTM terminals either by local dendrites or by axon terminals. We discuss the possibility that these GABAergic synapses can be driven by inputs from both primary afferents and/or descending systems to modulate the transmission of nociceptive sensory information. PMID- 1494941 TI - Segregation of presynaptic inputs on an identified target neuron in vitro: structural remodeling visualized over time. AB - Sensory cells of Aplysia form chemical synapses with the motor cell L7 in culture. Under certain conditions, sensory cells will also form electrical connections with each other. Sites of chemical synaptic interaction between the sensory cells and L7 are located at varicosities along sensory cell processes that overlie the main axons of L7, since these structures have been shown ultrastructurally to contain active zones. Previous studies have suggested that the distribution of sensory cell varicosities can be restricted to exclusive regions of the motor cell by the presence of other sensory cells. We wished to investigate (1) how this segregated pattern is generated over time and (2) whether electrical coupling between sensory cells has an effect on this segregated pattern. Using fluorescent dye injection and low-light video microscopy, we visualized the distribution of varicosities for each of two sensory cells growing on L7. In cases in which sensory cells are not electrically coupled, the varicosities from these two cells are spatially segregated on the target after 4 d in culture but not after 2 d in culture. Examination of the varicosity distribution of the same sensory cells on the second and third day of growth indicated both an increased rate in the elimination of varicosities from previously occupied areas and a restriction of varicosity formation in new areas of the target when a second sensory cell is present. For sensory cells that are electrically coupled, varicosities from these cells were not spatially segregated on the target even after 4 d in culture. These observations in vitro suggest that segregation of synaptic inputs by Aplysia sensory cells, which show little spontaneous activity of action potentials, can emerge over time via a process that includes both the elimination of existing sensory varicosities and the restriction of new varicosity formation. Our results also suggest that electrical connections between presynaptic cells can disrupt the segregation of their varicosities on a target, resulting in significant changes in the developing connectivity. PMID- 1494940 TI - Neurophysiological correlates of hand preference in primary motor cortex of adult squirrel monkeys. AB - Variability in the functional topography of area 4 was examined in adult squirrel monkeys. Conventional intracortical microstimulation techniques were used to derive detailed maps (250 microns interpenetration distances) of distal forelimb movement representations in both hemispheres of six monkeys. Spatial features of these representational maps were then compared to the hand preferred by the individual animals during a motor task requiring skilled digit use. Beyond a few broad generalizations common to all area 4 motor maps, the local mosaic-like topography of individual distal forelimb representations was highly idiosyncratic. Using statistical procedures to determine the independent contributions of individual, side, and movement category to the total variation in motor maps, the results demonstrate statistically significant variation in representational topography among individuals as well as between hemispheres of the same individuals. In the dominant hemisphere (i.e., the hemisphere opposite the preferred hand), the distal forelimb representations generally were greater in number and larger in total area, and displayed a longer total boundary length and a greater index of spatial complexity. Because of the direct relationship between interhemispheric asymmetry and behavioral asymmetry, these studies suggest that a large source of variability found in the topography of motor maps in this and other studies derives from differences in the way particular movements and/or movement combinations are performed by individual animals. PMID- 1494942 TI - Divalent-selective voltage-independent calcium channels in Lymnaea neurons: permeation properties and inhibition by intracellular magnesium. AB - Calcium channels are tightly regulated. Voltage-gated calcium channels open only in response to depolarization, while voltage-independent calcium channels usually open only in response to specific intracellular or extracellular ligands. Voltage independent calcium channels have been described in several invertebrate neurons. One difficulty in understanding the function of the neuronal channels is that their regulators are unknown. They open rarely in intact cells but are activated by formation of a cell-free patch, suggesting that some intracellular inhibitor usually keeps them closed. This article provides evidence that intracellular Mg2+ is one important regulator of the voltage-independent calcium channel (HP channel) in neurons of the pond snail Lymnaea stagnalis. Mg2+ (1 mM) rapidly and reversibly inhibited activity of this calcium channel when applied to the intracellular side of cell-free membrane patches. The primary effect of the Mg2+ was to promote long closings of the channel. The mechanism of the intracellular Mg2+ inhibition is distinct from open channel block, a phenomenon seen in a variety of cation channels. Open channel block can also be seen in the HP channels, but only at very positive membrane potentials. Some of the permeability and selectivity characteristics of these channels were also examined. The channels are permeable to Mg2+ and Ca2+ as well as Ba2+. Outward currents carried by monovalent cations can be observed only at very positive membrane potentials, indicating high selectivity for divalent over monovalent cations. The single channel current-voltage relationship is markedly nonlinear, becoming quite shallow near the reversal potential, and hence is qualitatively similar to that seen in many voltage-activated calcium channels. PMID- 1494943 TI - Heat shock protein expression in vulnerable cells of the rat hippocampus as an indicator of excitation-induced neuronal stress. AB - The inducible 72 kDa heat shock protein (HSP72) has been shown to be protective in non-neuronal cells and neurons in culture, but its function and the control of its expression in the CNS are poorly understood. Although HSP72 is induced in neurons in vivo by neurotoxic compounds that produce seizures and neuronal damage, it is unknown if its expression is a specific response to excitation per se or to "stressful" or potentially injurious excitation, or if it is a marker or mediator of irreversible injury. We have attempted to identify the nature of the stimulus for HSP72 expression by utilizing focal electrical stimulation that can either excite or destroy postsynaptic cells, depending on the duration of afferent stimulation. Previous studies have demonstrated that intermittent stimulation of the main hippocampal afferent pathway for 24 hr evokes synchronous discharges in dentate granule cells but does not injure them. However, the same stimulation irreversibly destroys three of the four cell populations innervated by the granule cells. The three vulnerable populations are the dentate hilar mossy cells, the somatostatin/neuropeptide Y (NPY)-immunoreactive hilar neurons, and the CA3c pyramidal cells. The fourth and relatively resistant population is the GABA-immunoreactive dentate basket cells. In this study, we have localized HSP72 expression immunocytochemically in the hippocampal dentate gyrus in response to nontoxic durations of potentially neurotoxic afferent stimulation.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1494944 TI - Identification and developmental expression of a novel low molecular weight neuronal intermediate filament protein expressed in Xenopus laevis. AB - Xenopus laevis is a valuable model system for the study of vertebrate neuroembryogenesis. However, very few well-characterized nervous system-specific molecular markers are available for studies in this organism. We screened a X. laevis adult brain cDNA library using a cDNA probe for mouse low molecular weight neurofilament protein (NF-L) in order to identify neuron-specific intermediate filament proteins. Clones for two distinct neuron-specific intermediate filament proteins were isolated and sequenced. One of these encoded for a Xenopus NF-L (XNF-L) and the other for a novel neuron-specific Xenopus intermediate filament protein (XNIF) that was present earlier and more abundantly than XNF-L during development. XNIF contained a central rod domain with multiple sequence features characteristic of IF proteins. The XNF-L was very similar to mouse NF-L, with a 77% sequence identity in the rod domain and the presence of a polyglutamic acid region in the tail domain, characteristic of type IV neurofilament proteins. In contrast, XNIF showed only 60% identity to mouse NF-L in the rod domain and lacked the glutamic acid-rich sequence in the tail domain. XNIF also had a very low (approximately 38%) sequence identity in the head and tail domains as compared to NF-L and other neurofilament proteins (45% identity to the head domain of alpha-internexin). In the adult frog, XNIF mRNA is detected by Northern blots only within the nervous system and by in situ hybridization histochemistry exclusively in neurons, particularly in the medullary reticular system and spinal cord. Antisera raised against the unique tail region of XNIF detected a single distinct 60 kDa band in Western blots of nervous system cytoskeletal preparations, and this XNIF immunoreactivity was concentrated in axons in the PNS and in small perikarya in the dorsal root ganglion. In contrast, NF-L immunoreactivity was principally in the large perikarya in the dorsal root ganglion. In development, XNIF mRNA appears more abundant than XNF-L mRNA in all premetamorphic stages examined. XNIF mRNA is first detectable at stage 24 (26 hr), whereas stable expression of XNF-L is at stage 35/36 (50 hr). XNIF immunoreactivity is detectable within the cement gland, within many neuronal cell bodies and axon tracts within the developing nervous system, and within all cellular layers of the developing retina. The availability of these two distinct neuron-specific intermediate filament proteins, with different temporal and spatial expression patterns, should provide new markers as well as targets for functional perturbation in the developing X. laevis nervous system. PMID- 1494945 TI - Formation of specific afferent connections in organotypic slice cultures from rat visual cortex cocultured with lateral geniculate nucleus. AB - The development of the cerebral cortex involves the specification of intrinsic circuitry and extrinsic connections, the pattern of inputs and outputs. To investigate the development of a major afferent input to the cortex, we studied the formation of thalamocortical connections in an organotypic culture system. Slices from the lateral thalamus of young rats were cocultured with slices from the visual cortex. Thalamocortical projections in vitro were examined anatomically with fluorescent dyes and physiologically with electrophysiological and optical recording techniques. Axons emerged from thalamic explants radially in all directions. The outgrowth of thalamic fibers and the course of the axonal trajectories were not influenced by the presence of the cocultured cortex. Only those thalamic axons that happened to grow toward the cortical slices invaded their target tissue. Thalamocortical projection cell in vitro had the characteristic morphology of thalamic relay neurons. Cells with the morphology of interneurons were present in thalamic explants, but these neurons did not project to the cocultured cortex. Thalamocortical axons in vitro terminated in their appropriate cortical target layer, formed axonal arbors, and made functional synaptic contacts. Such specific connections between thalamic neurons and their cortical target cells were established regardless of whether thalamocortical axons invaded the cortex from the white matter side or from the pial surface. These results suggest that thalamic projection neurons have an innate mechanism that allows them to recognize their cortical target cells. Thus, intrinsic factors play a significant role in the laminar specification of cortical connections during development. PMID- 1494946 TI - Phosphorylation of DARPP-32 and protein phosphatase inhibitor-1 in rat choroid plexus: regulation by factors other than dopamine. AB - The molecular mechanisms underlying regulation of fluid production by secretory epithelia such as the choroid plexus are poorly understood. Two cAMP-regulated inhibitors of protein phosphatase-1, inhibitor-1 (I1) and a dopamine- and cAMP regulated phosphoprotein, M(r) = 32,000 (DARPP-32), are enriched in the choroid plexus. We show here that these two phosphoproteins are colocalized in choroid plexus epithelial cells. We have developed a novel method for studying the phosphorylation state of DARPP-32 and I1 in intact cells, using a phosphorylation state-specific monoclonal antibody. Several drugs and hormones that are known to alter fluid secretion and that increase cAMP levels (forskolin, isoproterenol, vasoactive intestinal peptide) or cGMP levels (atrial natriuretic peptide) or that may use additional second messenger pathways (5-HT), increase the phosphorylation of I1 and DARPP-32 in rat choroid plexus. In contrast, dopamine does not alter cAMP and cGMP levels, or I1 and DARPP-32 phosphorylation. Our results indicate that DARPP-32, known to be regulated by dopamine in a number of tissues, can be phosphorylated in response to non-dopaminergic factors, including hormones acting through non-cAMP-dependent pathways. Our results also raise the possibility that inhibition of phosphatase-1, as a result of I1 and DARPP-32 phosphorylation, might be part of a final common pathway in the action of several factors that are known or thought to alter cerebrospinal fluid production. PMID- 1494947 TI - Synaptic pharmacology of the superior olivary complex studied in mouse brain slice. AB - The synaptic pharmacology of the lateral superior olive (LSO) and medial nucleus of the trapezoid body (MNTB) was examined in a brain slice preparation of the mouse superior olivary complex (SOC). Physiological responses in SOC were elicited by electrical stimulation of the trapezoid body ipsilateral or contralateral to the recording site, and bilateral interactions were investigated by combined ipsilateral and contralateral stimulation. Pharmacological effects were tested by bath application of amino acid agonists and antagonists. Neurons in MNTB were excited by contralateral stimulation and unaffected by ipsilateral stimulation. Excitatory amino acid (EAA) agonists--kainic acid (KA), quisqualic acid (QA), or L-glutamate--caused spontaneous firing at low concentrations and eliminated responses at higher concentrations in MNTB. The EAA agonist NMDA had relatively little effect at comparable concentrations. Stimulus-elicited responses were blocked by non-NMDA antagonists 6-cyano-7-nitroquinoxaline-2,3 dione (CNQX) and 6,7-dinitro-quinoxaline-2,3-dione (DNQX) and by the nonspecific EAA antagonist kynurenic acid, but were unaffected by the NMDA antagonist D,L-2 amino-5-phosphonovaleric acid (APV). LSO neurons were typically excited by ipsilateral stimulation and inhibited by contralateral stimulation. In LSO, KA, QA, and L-glutamate caused spontaneous firing at low concentrations and eliminated responses at higher concentrations, and NMDA had relatively little effect. Excitatory responses in the vast majority of LSO neurons were blocked by CNQX, DNQX, or kynurenic acid. Some responses were also blocked by APV. LSO neurons were affected by glycine, and contralateral inhibition in LSO was completely blocked by strychnine. NMDA also blocked inhibition in LSO. These results indicate that excitation of both MNTB and LSO neurons is mediated primarily by an EAA neurotransmitter through non-NMDA receptors and that contralateral inhibition of LSO cells is mediated through strychnine-dependent glycine receptors. NMDA receptors may play a role in binaural processing by modulating contralateral inhibitory input to LSO. PMID- 1494948 TI - Comparative migration and development of astroglial and oligodendroglial cell populations from a brain xenograft. AB - In previous studies of brain transplantation, the fate of the implanted glial cells has been investigated separately; that is, the interest has been focused either on the astroglia or on the oligodendroglia. However, the two populations of implanted glial cells may interact with each other, for example by secreting species-specific factors or by inducing reactions by the host. We have used two different models of brain transplantation: one that allows the identification of the implanted astrocytes, and another that allows the identification of the implanted oligodendroglia. The present model is a combination of both; it consists of the grafting of embryonic rabbit brain fragments into the brains of neonatal Shiverer mice. The myelin made by the implanted oligodendrocytes is identified by anti-myelin basic protein immunohistochemistry. The implanted astrocytes are identified by a monoclonal antibody that combines with rabbit but not with mouse glial fibrillary acidic protein. This study shows that although they use the same major routes of migration, both populations of glial cells tend to move differently. They demonstrate areas of common settlement but also areas where only one population of implanted glia is present. From the site of implantation in the dorsal striatum, the major routes of migration are the corpus callosum, the white matter fascicles in the striatum, and the internal capsule. After a delay of 6 weeks, no significant prevalence of one population of implanted glial cells over the other was observed. PMID- 1494949 TI - Polysialic acid is required for optimal growth of axons on a neuronal substrate. AB - Formation of axonal pathways involves a variety of molecules that influence cell cell interactions. The polysialic acid (PSA) moiety of the neural cell adhesion molecule (NCAM) is present on neuronal surfaces during process outgrowth. Our studies reveal that the removal of PSA causes a decrease in the rate of elongation of retinal cell processes on a substrate of neuronal membranes derived from chick tectum. This effect was partially reversed by antibodies against the L1 adhesion molecule, but not by antibodies against NCAM, N-cadherin, or beta 1 integrins. This predominant effect of PSA on L1 was also observed in short-term, cell-cell adhesion assays, suggesting that PSA promotes optimal outgrowth on neuronal substrates by limiting the consequences of L1-mediated adhesion. PMID- 1494950 TI - Differential imaging of ocular dominance and orientation selectivity in monkey striate cortex. AB - Differential images of ocular dominance, acquired by comparing responses to the two eyes, reveal dark and light bands where cortical cells are dominated by the right and left eyes. These include most (but not all) histochemically stained cytochrome oxidase blobs in their centers. Differential images of orientation, acquired by comparing responses to orthogonal orientations, reveal dark and light bands that are reminiscent of the "orientation columns" reported earlier, on the basis of 2-deoxyglucose (2DG) autoradiograms (Hubel et al., 1978). However, they are shorter and more fragmented because they do not include regions lacking selectivity for orientation. Even though these "bands" derive from orientation selective areas, comparisons with differential images of other orientations reveal that regions along their centers prefer different orientations. Hence, the orientation preferences inferred from "bands" in single differential images, or single 2DG autoradiograms, are not necessarily incorrect. Interactions between ocular dominance and orientation were investigated by comparing differential images of orientation obtained with binocular and monocular stimulation, as well as by comparing differential images of ocular dominance obtained with different orientations. In both cases, the elicited interactions were minimal, indicating a remarkable and unexpected independence that subsequent experiments revealed arises, at least in part, from a lateral segregation of regions most selective for one eye and regions most selective for one orientation, in the centers and edges of ocular dominance columns. Since this can also be viewed as a lateral correlation between binocularity and orientation selectivity, it fits with the simultaneous emergence of these properties in layers receiving input from layer 4c, and suggests that each of these properties requires the other. PMID- 1494951 TI - Regulation of neuronal growth cone filopodia by intracellular calcium. AB - Filopodia have been regarded as the sensory extensions of neuronal growth cones. As such, filopodia assay distant environments and are important for directing growth cones toward their targets. Since the territory encountered by a growth cone depends on the area spanned by the filopodia, changes in filopodial length or number result in the "exploration" of different-sized regions of the environment. The present study tests the potential regulatory role of intracellular calcium levels ([Ca2+]i) on filopodial morphology in identified neurons from the snail Helisoma. Experimentally evoked changes in [Ca2+]i were measured with the fluorescent calcium indicator fura-2 and directly correlated with growth cone filopodial morphology. A rise in [Ca2+]i caused two distinct, concentration-dependent effects separable by their different time courses: within the first 10 min, filopodia underwent significant elongation, while the second phase was characterized by a massive loss of filopodia. Both of these behaviors were increased in a calcium-dependent fashion. The magnitude of both filopodial elongation and filopodial loss correlated well with the transient peak values of [Ca2+]i reached during a given experimental treatment (r less than or equal to 0.98). In addition to the direct effect of the initial transient rise in [Ca2+]i, there is evidence for a form of adaptation of filopodial behavior to sustained calcium levels. A transient change in [Ca2+]i of as little as 30-50 nM reliably altered filopodial morphology. These results indicate that even small changes in intrinsic calcium homeostatic properties or extrinsic signals that alter intracellular calcium levels can act as regulators of the size of the environment sampled by an elongating growth cone. PMID- 1494952 TI - Sulforhodamine labeling of neural circuits engaged in motor pattern generation in the in vitro turtle brainstem-cerebellum. AB - A fluorescent molecular probe was used in combination with a novel in vitro preparation to study spatial patterns of neural activity associated with motor pattern generation. The in vitro brainstem-cerebellum preparation takes advantage of the turtle's unusual resistance to anoxia to preserve the entire neural network that connects the cerebellum, red nucleus, and reticular formation. This preparation was bathed in a 0.01% solution of sulforhodamine while it was activated unilaterally by electrical stimulation of the dorsal quadrant of the spinal cord for 1 hr. Sulforhodamine is a small, sulfonated, highly charged fluorescent molecule that is taken up by endocytosis. To examine its distribution in the cerebellum and brainstem, coronal sections were prepared and viewed under epifluorescence illumination. Distinctive spatial patterns of labeling were associated with unilateral electrical stimulation of the in vitro network, suggesting that dye uptake was activity dependent. Blockade of uptake with altered magnesium and calcium concentrations indicated that single spike discharge evoked ortho- or antidromically was insufficient to induce dye uptake. Instead, sulforhodamine staining correlated with the presence of burst discharge that was recorded extracellularly from the red nucleus. Blockade of burst discharge with excitatory amino acid receptor antagonists prevented dye uptake in the red nucleus, the lateral cerebellar nucleus, and other structures that are known to be interconnected by recurrent anatomical pathways. These results suggest that sulforhodamine is internalized by intensely active neurons. The spatial distributions of label support the hypothesis that burst discharges in the turtle red nucleus are mediated by excitatory amino acid neurotransmitters and sustained by recurrent excitation in cerebellorubral synaptic pathways. Positive feedback in these recurrent pathways may provide an important driving force for the generation of motor programs that control limb movements. PMID- 1494953 TI - A comparison of the interaural time sensitivity of neurons in the inferior colliculus and thalamus of the unanesthetized rabbit. AB - The localization of low-frequency sounds (less than 3 kHz) along the azimuth involves comparing the ongoing difference in the time of arrival of a sound at the two ears. Information about interaural time differences (ITDs) is derived from an initial comparison performed in the superior olivary complex. However, little is known about which aspects of this information are transformed as it ascends the brainstem. To address this issue, we compared the ITD sensitivity of neurons in the inferior colliculus (IC) and auditory thalamus, successive stations in the auditory pathway. We found ITD sensitivity in the IC and thalamus to be similar in several respects. At both levels, the large majority of neurons responded maximally to ITDs within the range that a rabbit would normally encounter (+/- 300 microseconds) and preferred ipsilateral delays, delays that would be created by sounds in the contralateral sound field. The range of frequencies over which ITD sensitivity was expressed was also similar in the midbrain and thalamus. Several differences were also apparent. In comparison to IC neurons, neurons in the thalamus responded over more restricted ranges of ITD, responded at lower rates, and, in response to monaural stimulation, showed an increased influence of inhibition. Finally, a greater proportion of thalamic units had characteristic delays corresponding to intermediate discharge rates. The preservation of a bias for ipsilateral delays from IC to thalamus suggests that a representation of contralateral azimuths is present at both levels. Similarities between the two levels suggest that information about ITDs is faithfully transmitted from midbrain to thalamus. Differences in ITD sensitivity, such as the sharper tuning for ITDs, suggest that the thalamus is not a simple relay. Enhanced sensitivity to ITDs should translate to better-defined azimuthal receptive fields, and therefore may be a step toward achieving an optimal representation of azimuth within the auditory pathway. PMID- 1494954 TI - Induction of motor neuron sprouting in vivo by ciliary neurotrophic factor and basic fibroblast growth factor. AB - Ciliary neurotrophic factor (CNTF) and basic fibroblast growth factor (bFGF) were tested for effects on sprouting by motor neurons innervating the adult mouse gluteus muscle. Factors were delivered by subcutaneous injection directly over the surface of the superior gluteus muscle once daily for 7 d and then end plates and axons were visualized by combined silver and cholinesterase staining. CNTF (500 ng daily) induced sprouting both from end plates and from the subset of nodes of Ranvier that are closest to the end plate. The effect of CNTF was potentiated twofold by coadministration of bFGF at doses of 2-20 ng daily, whereas treatment with bFGF alone failed to induce sprouting from either end plates or nodes of Ranvier. The sprouting stimulus delivered by the factors showed limited penetrance into the muscle and restricted lateral spread from the injection site. PMID- 1494955 TI - Dynamics of terminal arbor formation and target approach of retinotectal axons in living zebrafish embryos: a time-lapse study of single axons. AB - In a variety of species, developing retinal axons branch initially more widely in their visual target centers and only gradually restrict their terminal arbors to smaller and defined territories. Retinotectal axons in fish, however, appeared to grow in a directed manner and to arborize only at their retinotopic target sites. To visualize the dynamics of retinal axon growth and arbor formation in fish, time-lapse recordings were made of individual retinal ganglion cell axons in the tectum in live zebrafish embryos. Axons were labeled with the fluorescent carbocyanine dyes Dil or DiO inserted as crystals into defined regions of the retina, viewed with 40x and 100x objectives with an SIT camera, and recorded, with exposure times of 200 msec at 30 or 60 sec intervals, over time periods of up to 13 hr. (1) Growth cones advanced rapidly, but the advance was punctuated by periods of rest. During the rest periods, the growth cones broadened and developed filopodia, but during extension they were more streamlined. (2) Growth cones traveled unerringly into the direction of their retinotopic targets without branching en route. At their target and only there, the axons began to form terminal arborizations, a process that involved the emission and retraction of numerous short side branches. The area that was permanently occupied or touched by transient branches of the terminal arbor--"the exploration field"--was small and almost circular and covered not more than 5.3% of the entire tectal surface area, but represented up to six times the size of the arbor at any one time. These findings are consistent with the idea that retinal axons are guided to their retinotopic target sites by sets of positional markers, with a graded distribution over the axes of the tectum. PMID- 1494956 TI - Habenula and thalamus cell transplants mediate different specific patterns of innervation in the interpeduncular nucleus. AB - Innervation of specific peptidergic and cholinergic compartments of the interpeduncular nucleus (IPN) was investigated using embryonic cell suspension transplants immunoreactive for substance P (SP) and ChAT. In both neonatal and adult host rats, the IPN was first denervated of its normal SP and cholinergic input from the medial habenula by bilateral lesions of the fasciculi retroflexi (FR). In adult hosts, transplants of embryonic habenular cells placed near the denervated IPN mediated a return of the normal pattern of SP staining restricted to habenula-target subnuclei, plus an increase in staining intensity of SP cells intrinsic to the IPN. There was no recovery of ChAT staining. A similar pattern of SP staining resulted following habenular transplants into neonatal hosts, but in addition there was a partial recovery of normal ChAT staining in cholinergic subnuclei and anomalous ChAT staining in normally peptidergic subnuclei. Control transplants of embryonic thalamus cells placed into adult hosts produced a surprising pattern of ChAT staining in the IPN identical to that seen with habenula transplants placed into neonatal hosts; the adult IPN was thus able to support reinnervation mediated by an aberrant cholinergic source while being refractory to its normal habenular cholinergic afferents. This pattern of results implies regulation by the IPN of habenular SP and cholinergic innervation, and some interaction between the maturing normal cholinergic afferents and their targets that is missing when these afferent sources are abnormal. PMID- 1494957 TI - Habenula and thalamus cell transplants restore normal sleep behaviors disrupted by denervation of the interpeduncular nucleus. AB - The preceding companion study (Eckenrode et al., 1992) showed that cell suspension transplants of fetal habenula cells placed near the interpeduncular nucleus (IPN) following lesions of the fasciculus retroflexus (FR) restore the normal pattern of substance P (SP) staining in habenular target subnuclei of the IPN in both perinatal and adult hosts, and restore ChAT staining in the IPN of perinatal hosts. Similarly placed transplants of fetal thalamus cells only restore ChAT staining in the IPN of adult hosts. In this study, we examined the functional significance of these restored staining patterns. We used a behavioral measure of the integrity of REM-stage and non-REM-stage sleep, the "flower pot" test, and assayed (1) normal adult rats, (2) FR-lesioned control animals (neonatal or adult operates), (3) animals receiving FR lesions and transplants of fetal habenula cells (perinatal or adult hosts), and (4) animals receiving FR lesions and transplants of fetal thalamus cells (adult hosts). FR lesions decrease markedly the muscle atonia component of REM sleep and reduce duration of sleep episodes. Transplants that restore SP staining in the IPN (habenular transplants into either perinatal or adult lesion hosts) restore normal frequency of REM atonia; transplants that restore ChAT staining (habenular transplants into perinatal hosts or thalamic transplants into adult hosts) restore normal duration of sleep episodes. The number of SP-immunoreactive cells in the transplants predicts recovery of REM atonia, and the number of ChAT cells in habenular (but not thalamic) transplants predicts restoration of sleep duration.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1494958 TI - Chronic low-level exposure to benzene. PMID- 1494959 TI - Finger systolic blood pressure measurements after finger cooling. Using the laser Doppler method for assessing vibration-induced white finger. AB - Finger systolic blood pressure (FSBP) measurements after finger and body cooling using a strain-gauge plethysmograph is a useful objective test for diagnosing Raynaud's phenomenon (RP). Body cooling, however, is uncomfortable to subjects. In this study, the measurements of FSBP after finger cooling without body cooling, using Digitmatic DM2000 (Medimatic) combined with laser-Doppler flowmetry (ALF2100 Advance), were performed in 99 vibration-exposed men (40 men without RP, 39 men with mild RP, and 20 men with severe RP) and 13 healthy controls. This method is relatively useful for assessing the severity of vibration-induced white finger (VWF). PMID- 1494960 TI - Activation of blood platelets in workers exposed to organic solvents. AB - Organic solvents probably exert their clinical effects through distortion of cellular membrane structure and function. Blood platelets represent an easily available membrane system. This study describes an evaluation of mean platelet volume (MPV) and total platelet count (TPC) in a group of workers exposed to a mixture of organic solvents in paint factories. We have found a correlation between decreased MPV and present exposure. The reduction was reversed within an exposure-free interval of 3 weeks. The intracellular adenosine triphosphate/adenosine diphosphate (ATP/ADP) ratio was significantly increased in exposed workers, compatible with dense granule secretion. A quantitative study of the phosphoinositide cycle in the platelets revealed an increased concentration of the phosphatidic acid, indicating an increased turnover. These findings are consistent with a solvent-induced activation of circulating platelets. PMID- 1494961 TI - Workplace smoking restrictions, occupational status, and reduced cigarette consumption. AB - Reductions in workday cigarette consumption among indoor workers subject to different levels of smoking restriction were examined using representative population data for both blue-collar and white-collar workers. Regardless of whether workplace smoking bans were total or applied only to the usual work station, reported workday cigarette consumption was reduced by approximately five cigarettes per day compared with leisure-day consumption. This was in contrast to there being no difference between workday and leisure-day consumption among those who had no ban on smoking at their usual work station. This pattern of findings applied to all occupational-status groups, after controlling for sex and number of cigarettes smoked on a leisure day. These results are discussed with reference to potential public-health benefits and to implications for reduced retail sales of cigarettes. PMID- 1494962 TI - Persistent brominated and chlorinated dioxin blood levels in a chemist. 35 years after dioxin exposure. AB - This is the first report on occupational health hazards to dioxin chemists associated with laboratory exposure to 2,3,7,8-tetrabromodibenzodioxin (TBrDD), and further characterizes the human response to 2,3,7,8 tetrachlorodibenzodioxin (TCDD). In this case study the chemist was exposed on two separate occasions. In March 1956, after synthesizing 10 g of TBrDD, the chemist suffered from mild and transient chloracne of the neck and wrists; in September 1956, after synthesizing 16 g of TCDD, he suffered severe chloracne of the entire body, headaches, backache, and leg pain on exertion. His measured 2,3,7,8-TBrDD in 1991 was 625 parts per trillion (ppt) in whole blood lipid, 35 years after initial exposure and 18 ppt TCDD, an elevated level in comparison with the mean 2,3,7,8-TCDD level of 5 ppt in the US population. This is the first reported detection of a brominated dioxin in human tissue. The total halogenated dioxin body burden in September 1956 is estimated to have been between 13,005 ppt and 146,726 ppt. This amount can be considered to be, at least in this person, a strong chloracnegenic dose, and a dose causing human nervous system and muscular or circulatory system responses. This uptake demonstrates an occupational hazard to chemists and chemical workers, and the usefulness of human tissue dioxin measurements to document absorption. PMID- 1494963 TI - Mental health, constraints, and organization of work as interactive variables. A study of word processing secretaries. AB - The effect of a work constraint is specific to the type of work organization. This article deals with the effects of different types of work organization on the mental health of secretaries. The advantage of choosing secretarial work as a research subject lies in the fact that we can identify three distinct types of work organization: (1) a secretary working directly for someone (the "paired" secretary-boss), (2) the "pool," geared toward keyboard input with no specific pairing of secretaries and authors, and (3) the departmental "team," a hybrid of the two preceding types, characterized by the presence of several secretaries, each one assigned to several authors. A study was conducted on the health problems reported by secretaries in the Quebec civil service. Data available from a Sante Quebec study, carried out at the same time, allowed us to constitute a general population reference group of secretaries and other working women. The findings indicate that secretaries in the general population are no more at risk than are other similar working women, but that secretaries in the provincial civil service are at risk. Regression analysis shows that the same traditional constraints do not affect secretaries in the same way regardless of whether they are members of pair, pool, or team organizations. This suggests that the context of work organization is an interactive or a "specifying variable" of the effect of work constraints on the secretaries' mental health. PMID- 1494964 TI - The impact of legislation on self-reported safety belt use in a working population. AB - To assess the impact of safety belt laws, we compared self-reported use of safety belts among employed residents of states with primary, secondary, and no laws in a group of 17,830 volunteer health profile participants. Failure to wear safety belts at least 80% of the time was reported by 22% of subjects covered by primary laws, 23% of those covered by secondary laws, and 39% of those not covered by any law. PMID- 1494965 TI - Latent period for malignant mesothelioma of occupational origin. AB - To estimate the minimal latent period for malignant mesothelioma of occupational origin, we reviewed 21 articles that documented latent periods for malignant mesothelioma, totaling 1690 cases. Of these, 1105 (65%) cases fulfilled the strict histologic and exposure criteria and were included in this analysis. Of these mesotheliomas, 99% had a latent period more than 15 years; 96% had a latent period of at least 20 years; and the observed probability of an occupational exposure within a decade of the first exposure was zero. The estimated median latent period was at least 32 years after the initial exposure. These epidemiologic conclusions are important in determining the source of a specific case of the disease, understanding the natural history of the disease, determining liability, and in aiding in the diagnosis of malignant mesotheliomas of occupational origin. PMID- 1494966 TI - Mental and psychosomatic work injuries in Sweden. AB - In Sweden, persons who incur illness or injury at work or on the way to or from work may claim indemnity under a work injuries insurance scheme. A new law in 1977 included mental and psychosomatic illnesses. Looking into the records of reported work injuries in Gothenburg 10 years later, we found 67 cases diagnosed as mental or psychosomatic illnesses. One third of these were accepted as work injuries. The cited harmful influence mostly referred to mental and/or physical strain from work itself. Traumatic incidents, maltreatment by the employer, and persecution also were accepted as harmful influences. Comparison with an earlier study revealed that although the rate of approbation for mental and psychosomatic work-related illnesses (about 30%) is much lower than for all work-related illnesses (about 90%), there has been a considerable increase over the years. PMID- 1494967 TI - Use of medical insurance claims for surveillance of occupational disease. An analysis of cumulative trauma in the auto industry. AB - Medical insurance claims, linked with work histories for a large automotive manufacturer over a 3-year period, identified large numbers of cases of potentially work-related diseases, including 30,600 episodes of probable cumulative trauma disorders (CTD). CTD incidence rates were calculated within five plants, and high-risk areas identified, however, unknown differences in medical insurance coverage by exposure group limited interpretation. Case-control analyses, with controls also identified by insurance claims, addressed coverage and produced age-adjusted and sex-adjusted estimates of risks. All five plants had departments with statistically significant, elevated risks for one or more of the diagnoses carpal tunnel syndrome, CTD of other upper extremities, rotator cuff syndrome, CTD of the neck and of the lower back. Medical insurance claim data linked with work history provide the basis for practical and comprehensive surveillance for CTD and potentially a variety of other occupational diseases. PMID- 1494968 TI - Primary care: in rural America and your own backyard. PMID- 1494969 TI - Nurses' role in preventing birth defects in offspring of women with phenylketonuria. AB - Most women who began nutrition support as neonates for a diagnosis of phenylketonuria, an inherited defect in phenylalanine metabolism, are of normal intelligence, no longer require a restricted diet, and wish to have children of their own. Phenylketonuria that is untreated when a woman conceives and during gestation results in poor reproductive outcomes. Treatment with and careful monitoring of a phenylalanine-restricted diet can improve reproductive outcome. Nurses have the primary responsibility in locating women of childbearing age with phenylketonuria; developing strategies to improve palatability of the diet, thereby enhancing compliance; providing ongoing monitoring and support of the mother-child dyad; and counseling couples at risk. PMID- 1494970 TI - Improving access to and use of prenatal care. AB - Inadequate prenatal care is one of the most perplexing problems in obstetrics. Many women do not seek prenatal care early, and some obtain no prenatal care. The history of prenatal care, the impact of inadequate prenatal care, and the many factors involved in access to and use of prenatal care are discussed. Nursing implications aimed at exploring ways of reducing these factors are examined. PMID- 1494971 TI - Maternity blues and postpartum depression. AB - OBJECTIVE: To investigate the relationship between maternity blues and postpartum depression in mothers discharged early from the hospital and those discharged after the customary length of hospital stay. DESIGN: A descriptive correlation design. SETTING: 550-bed community and teaching hospital in the midwestern United States. PARTICIPANTS: 49 privately paying, primiparous, American-born women, 18 years of age or older, with uncomplicated pregnancies and vaginal deliveries of healthy neonates weighing 2,600-4,000 g. MEASURES: Stein Maternity Blues Scale and Beck Depression Inventory were used to collect data. RESULTS: No significant differences found between the two groups of mothers; significant relationships found between maternity blues at 1 week after delivery and postpartum depression at 6 and 12 weeks after delivery. CONCLUSIONS: Early discharge appears to pose no threat to psychologic well-being. Primiparas experiencing more severe maternity blues are at increased risk for postpartum depression. PMID- 1494972 TI - Biofeedback-assisted relaxation to reduce stress in labor. AB - OBJECTIVE: To test the feasibility and effectiveness of incorporating biofeedback assisted relaxation techniques into routine instruction in Lamaze classes. DESIGN: A quasi-experimental design (static groups comparison) was used. SETTING: Lamaze classes. PARTICIPANTS: A convenience sample of 33 subjects recruited from 12 Lamaze classes. MEASURES: Duration of first-stage labor, amount of sedation and analgesia during first-stage labor, number of complications, and 1- and 5 minute Apgar scores of the neonates. RESULTS: The experimental subjects reported greater stress during labor than did the control subjects. CONCLUSIONS: Although the supplementary instruction in reducing stress seemed to promote relaxation during the prenatal classes, it did not reduce distress during labor and delivery because no mothers attempted to use the technique at that time. PMID- 1494973 TI - Intrapartum care of a woman with aortic aneurysms. AB - Advances in technology and complex care have enabled women with various health problems to become and remain pregnant. Consequently, health-care practitioners are seeing an increasing number of pregnant women who have aortic aneurysms. This case study describes the culturally sensitive intrapartum care of a Middle Eastern woman with ascending and descending aortic aneurysms. PMID- 1494974 TI - After hysterectomy. PMID- 1494975 TI - Reanalysis of lambda max variations in the Stiles-Burch 10 degrees color-matching functions. AB - Individual differences in the color matches made by normal observers can be attributed in part to small interobserver variations in the spectral peaks (lambda max) of the cone sensitivities. I compared two different analyses of these lambda max variations that were both based on the Stiles-Burch 10 degrees color-matching functions [Opt. Acta 6, 1 (1959)]: one that suggested that the lambda max values for individual cone classes fall into discrete subgroups [J. Neitz and G. H. Jacobs, in Colour Vision Deficiencies IX, B. Drum and G. Verriest, eds. (Kluwer Academic, Dordrecht, The Netherlands, 1989)] and one that failed to find discrete clustering [J. Opt. Soc. Am. A 5, 1722 (1988)]. I conclude that there is not strong evidence for discrete lambda max variations in the Stiles-Burch matches. PMID- 1494976 TI - Effect of carrageenan-induced inflammation on the induction of hepatic microsomal enzymes by phenobarbital and benzo[a]pyrene in male rats. AB - The inhibitory effect of carrageenan-induced inflammation was examined by utilizing rats treated with inducers of this drug metabolizing system. Animals were given sodium phenobarbital (PB, 80 mg/kg, i.p., 24 h prior to death), or benzo[a]pyrene (BP, 40 mg/kg, i.p., 24 h prior to death) as inducers. Some animals were also given carrageenan 24 h prior to death. Non-induced male rats exhibited significant decreases in hepatic 9000 x g supernatant (S-9) cytochrome P-450 and aminopyrine (AM) N-demethylase, benzphetamine (BenzP) N-demethylase and meperidine (MP) N-demethylase activity following carrageenan treatment. Carrageenan also depressed the induction of hepatic S-9 cytochrome P-450 content caused by PB treatment, and suppressed the induction of AM, BenzP, MP, arylhydrocarbon and 7-ethoxycoumarine metabolism by PB treatment. Cytochrome P 450 levels and related biotransformation activity which are elevated by BP treatment were not decreased by the injection of BP and carrageenan simultaneously to male rats. Non-induced, PB-treated and BP-treated female rats did not show inhibited carrageenan-induced reduction in hemoprotein content or inhibition of AM-N-demethylase, BenzP N-demethylase and aniline hydroxylase activities. These results demonstrate the selective nature of the inhibitory effects of carrageenan-induced inflammation upon drug metabolism in the rats. PMID- 1494977 TI - Biochemical studies on oral toxicity of ricin. IV. A fate of orally administered ricin in rats. AB - After oral administration of ricin in rats, its distribution in the gastrointestinal tract, body fluids and principal organs was determined by an enzyme immunoassay, and the immunoreactive ricin detected was identified by gel filtration followed by sodium dodecyl sulfate polyacrylamide gel electrophoresis, protein blotting and the immunobinding method. When ricin D (10 mg/kg rat) was given orally to a rat, which dose is equivalent to 1/3 LD50, about 75% of the ricin was found in the stomach and small intestine within 2 h, and most of it was transferred to the large intestine after 24 h. It was also demonstrated by an in vitro toxicity test of immunoreactive ricin in the blood and lymph obtained from the intoxicated rats that a part of the ricin was absorbed from the small intestine into the tissues and organs via the circulatory systems (lymphatic and blood vessels) as the active ricin. The participation of the blood vessels was greater in the absorption of ricin from the gastrointestinal tract than that of the lymphatic system. Ricin, after absorption, was detected in liver and spleen and ricin found in the liver was predominantly in the form of intact ricin, although an undetectable amount of ricin in other organs cannot be eliminated. These results infer that a small fraction of orally-given ricin was transferred to the circulating system and was responsible for rat's death as in the case of i.p. administration. PMID- 1494978 TI - Pharmacokinetic analysis of amitriptyline and its demethylated metabolite in serum and brain of rats after acute and chronic oral administration of amitriptyline. AB - The compartmental model analysis by use of simultaneous curve fitting was carried out to ascertain the pharmacokinetic relationship between amitriptyline (AMT) and nortriptyline (NRT) in the serum and brain after acute or chronic oral administration of AMT. The estimated F value, a fraction of dose reached at systemic circulation, and the MD value, a fraction metabolized to NRT, were 0.044 and 0.020, respectively, after acute administration, indicating first-pass metabolism of AMT. The estimated parameters kin and kout, the transfer rate constants to and from the brain, showed no marked difference between AMT and NRT. These findings indicate equivalent ability of AMT and NRT to penetrate into the brain. The area under the concentration curve (AUC) values of AMT and NRT in the serum increased 1.4 and 8.2 times, respectively, with the increase of NRT being greater after chronic administration. The MD value was increased from 0.020 to 0.096, whereas the estimated F value showed no marked change. These results indicate the enhanced first-pass metabolism. The estimated transfer rate constants kin and kout of AMT were close to those of NRT. In addition, the transfer rate constants after chronic administration were similar to those after acute administration, indicating no marked change in penetration into the brain by multiple dosing. PMID- 1494979 TI - Distribution of quinidine in rats with carbon tetrachloride-intoxicated hepatic disease. AB - The disposition of quinidine was investigated in rats with experimental hepatic disease caused by an intraperitoneal injection of CCl4. The plasma disappearance of quinidine after a 12.5 mg/kg i.v. bolus injection was analyzed by a two compartment open model in both control and CCl4-intoxicated rats. In the CCl4 intoxicated rats, plasma total body clearance (CLtot), elimination rate constant of the central compartment (kel) and the volume of distribution (Vdss) of quinidine were decreased by 73, 51 and 36%, respectively, compared to those in the control rats. At a steady state of quinidine plasma concentration of 1 micrograms/ml, tissue-to-plasma partition coefficient (Kp,vivo) of the drug in the lung, spleen, heart, kidney and liver in the CCl4-intoxicated rats were decreased ranging from 32 to 42% compared to those in the control rats. The plasma free fraction of quinidine in the intoxicated rats was decreased by 34% of that in the control rats. Neither tissue binding of quinidien in vitro, nor plasma pH was altered in the intoxicated rats. Thus, the decrease in Vdss and Kp,vivo for quinidine in the intoxicated rats seems likely to be due to an increase in plasma protein binding of the drug. Metabolic activity in the liver, the hepatic extraction ratio for quinidine, and the hepatic blood flow in the CCl4-intoxicated rats were decreased by 84, 57 and 47%, respectively, compared to those in the control rats. The decrease in CLtot and kel in the intoxicated rats is considered to be attributed to both the reduction of liver functions and the increase in the plasma protein binding of the drug. PMID- 1494980 TI - Suppression by high glucose concentration of insulin receptor up-regulation in diaphragm and flexor digitorum brevis muscles from diabetic KK-CAy and streptozotocin-diabetic mice. AB - The specific binding of insulin to diaphragm and flexor digitorum brevis (FDB) muscles isolated from diabetic KK-CAy and streptozotocin (STZ)-diabetic ddY mice was investigated under high glucose concentration in vitro. For high-affinity insulin receptor under 2.8 mM glucose, amounts of the receptor and values of dissociation constant (Kd) were greater in both diabetic muscles than in the corresponding normal control muscles, respectively. High glucose concentration up to 16.7 mM reduced both the up-regulation of the receptor and the decrease in the affinity by the diabetic state. These studies strongly suggest that high glucose level in the diabetic state in vivo may suppress the up-regulation of high affinity insulin receptor in both models of diabetic mice. PMID- 1494981 TI - Accumulation of propranolol in cultured rat fibroblasts. AB - In order to clarify the involvement of phosphatidylserine (PhS) in the cellular accumulation of propranolol, we have characterized the binding of 3H-propranolol to cultured rat fibroblasts and to liposomes containing PhS. The properties of propranolol binding to the cells and liposomes were analyzed by means of a Scatchard plot. The cells contained at least two classes of propranolol binding sites, one site of high affinity/low capacity and the second site of lower affinity/higher capacity, while the liposomes contained only one class of binding site. The values of the association constant (K) and number of binding sites (n), given on a PhS basis for the propranolol binding site in the liposomes, were both very close to those of corresponding binding parameters for the high affinity/low capacity binding site in the cells. Cell death, caused by various toxic reagents, resulted in a marked decrease in propranolol accumulation in the cells. Kinetic analysis of the drug binding to dead cells showed one binding site with binding parameters comparable to those of the low affinity/high capacity binding site in the intact cells. Polar cations, methylamine and NH4Cl, completely inhibited propranolol binding to the liposomes. On the other hand, these cations partially inhibited propranolol accumulation in intact cells and failed to inhibit the drug binding to dead cells. These results suggest that PhS in cytomembranes represents the high affinity/low capacity propranolol binding site in cultured rat fibroblasts. PMID- 1494982 TI - Integration of the big five and circumplex approaches to trait structure. AB - To integrate the 5-dimensional simple-structure and circumplex models of personality, the Abridged Big Five Dimensional Circumplex (AB5C) taxonomy of personality traits was developed, consisting of the 10 circumplexes that can be formed by pitting each of the Big Five factors against one another. The model maps facets of the Big Five dimensions as blends of 2 factors. An application to data consisting of 636 self-ratings and peer ratings on 540 personality trait adjectives yielded 34 well-defined facets out of a possible 45. The AB5C solution is compared with simple-structure and lower dimensional circumplex solutions, and its integrative and corrective potential are discussed, as well as its limitations. PMID- 1494983 TI - Affect intensity and cardiac arousal. AB - Relationships between affect intensity and basal, evoked, and perceived cardiac arousal were investigated in 3 experiments. Affect intensity was assessed using Larsen and Diener's (1987) Affect Intensity Measure (AIM). Cardiac arousal was evoked with exercise in the 1st study and with mental arithmetic in the 2nd and 3rd. Perceived cardiac arousal was measured under optimal conditions using a standard heartbeat discrimination procedure. Women as a group scored higher on the AIM. Affect intensity was unrelated to basal or evoked cardiac arousal and was negatively related to perceived cardiac arousal in all 3 studies. Data suggest that affect intensity, although unrelated to actual physiological arousal, is negatively related to the accuracy with which individuals perceive their own arousal. Results are discussed within the context of an expanded arousal-regulation model (Blascovich, 1990). PMID- 1494984 TI - Self-fulfilling effects of stigmatizing information on children's social interactions. AB - The stigmatizing effects of negative expectancies were examined in observations of interactions between children with and without a behavior problem. Ss were 68 pairs of unacquainted boys in Grades 3-6. In each dyad, a normal boy was either told that his partner had a behavior problem or given no expectancy; this expectancy manipulation was crossed with the partner's actual diagnostic status with respect to hyperactivity. The perceivers' expectancy that their partner had a behavior problem as well as the actual diagnostic status of the target adversely affected the boys' interactions. Behavioral data suggest how the expectancies were communicated to the target. The processes underlying interpersonal expectancy effects and the ways in which a childhood stigma can act as a self-fulfilling prophecy are discussed. PMID- 1494985 TI - Possible self-complexity and affective reactions to goal-relevant evaluation. AB - The complexity of people's self-concept appears to be inversely related to the intensity of their reactions to evaluative feedback about present goals and abilities (Linville, 1985, 1987). The idea that the complexity of individuals' possible self-concept similarly mediates reactions to feedback regarding future goals was investigated. Two preliminary studies suggested that complexity of the actual self only explains 20% to 30% of the variance in possible self-complexity. Three studies were conducted. Support was found for the idea that possible self complexity mediates affective reactions to evaluative feedback about future goals and actual self-complexity mediates affective reactions to evaluative feedback about present goals. The findings underscore the independent roles of the organization of actual and possible self-concepts in affective processes. PMID- 1494986 TI - Emotional disclosure about traumas and its relation to health: effects of previous disclosure and trauma severity. AB - This study sought to replicate previous findings that disclosing traumas improves physical health and to compare the effects of revealing previously disclosed versus undisclosed traumas. According to inhibition theory, reporting about undisclosed traumas should produce greater health benefits. Sixty healthy undergraduates wrote about undisclosed traumas, previously disclosed traumas, or trivial events. Contrary to expectations, there were no significant between groups differences on longer term health utilization and physical symptom measures. However, Ss who disclosed more severe traumas reported fewer physical symptoms in the months following the study, compared with low-severity trauma Ss, and tended to report fewer symptoms than control Ss. Results suggest that health benefits occur when severe traumas are disclosed, regardless of whether previous disclosure has occurred. PMID- 1494987 TI - Evidence for genetic influences on personality from self-reports and informant ratings. AB - Self-report data on Extraversion (E) and Neuroticism (N), together with ratings by the co-twin, were obtained from a sample of 826 adult female twin pairs ascertained through a population-based twin register. Data were analyzed using a model that allowed for the contributions to personality ratings of the rater's personality (rater bias) as well as of the personality of the person being rated. For E, but not for N, significant rater bias was found, with extraverted respondents tending to underestimate, and introverted respondents tending to overestimate, the Extraversion of their co-twins. Good agreement between self reports and ratings by the respondent's co-twin was found for both E and N. Substantial genetic influences were found for both personality traits, confirming findings from genetic studies of personality that have relief only on self reports of respondents. PMID- 1494989 TI - Believing in yourself. PMID- 1494988 TI - [A multichannel telemetry system for autonomic neural signals, blood flow velocity, blood pressure, and ECG measurements]. AB - A radio multichannel telemetry system has been developed for use with chronically instrumented, unrestrained, small animals. The system can simultaneously record autonomic neural signals, blood flow velocity, blood pressure, and ECG. The system is time-multiplexed and pulse width modulation (PWM)/FM device, which employs two sampling frequencies. The system is designed with 10 standard low power integrated circuits, a 3 terminal voltage regulator, and a transistor. The size is 53 x 42 x 20 mm, and the weight, including two batteries is 40 grams. The system is powered by two lithium cells, which provide 60 hours of continuous operation. PMID- 1494990 TI - Ketorolac: a new parenteral nonsteroidal anti-inflammatory drug for postoperative pain management. AB - Providing adequate pain control with minimal side effects in inpatient and ambulatory settings is a continuous challenge to the PACU nurse. Ketorolac tromethamine (Toradol, Syntex, Palo Alto, CA) is a new parenteral nonsteroidal anti-inflammatory drug (NSAID) approved for use in the United States. Ketorolac is useful in the management of short term, moderate to severe postoperative pain. It is used by itself or as an adjunct to traditional opioid analgesics. Ketorolac, like other NSAIDs, has analgesic, anti-inflammatory, and antipyretic properties. Unlike morphine or meperidine, ketorolac does not bind to opioid receptors and is not a centrally acting agent. Administered intramuscularly, peak plasma levels are reached in 45 to 50 minutes. It is administered as a 30- or 60 mg intramuscular (IM) loading dose followed by 15- or 30-mg doses IM every 6 hours, with a maximum first-day dose of 150 mg and 120 mg on subsequent days up to a recommended maximum of 5 days. The lower dose range is recommended for elderly patients, patients weighing less than 50 kg, and patients with impaired kidney function. Initial studies show that use of ketorolac decreases the overall amount of opioid analgesia needed for postoperative pain control. To date, reported occurrence of side effects is low. A case study presents a healthy ambulatory surgical patient admitted for inguinal hernia repair using epidural anesthesia. Use of ketorolac has shown initial favorable results. More research is needed to further define its role and side effects in postoperative pain management. PMID- 1494991 TI - The effects of television viewing on preoperative anxiety. AB - Previous studies have looked at the relationship between preoperative anxiety and postoperative course. However, few studies have looked at methods to decrease preoperative anxiety. To investigate preoperative anxiety and possible anxiety reduction strategies, the investigators devised a clinical study to examine the effects of television viewing on preoperative anxiety. The study compared patients who were not able to watch television in the preoperative setting with those who were. The investigators hypothesized that television viewing in the preoperative setting would decrease preoperative anxiety. A purposive sampling method was chosen so that the study population could be selected using certain criteria. The sample consisted of adult patients 18 to 77 years old who were admitted to the preoperative area at least 2 hours before surgery. A total of 76 subjects participated in the study. However, due to incomplete data on seven of the questionnaires, 7 of the subjects were rejected. Of the remaining 69 subjects, 39 had no television access and the remaining 30 did. Statistical comparisons of the two groups suggest that there was a significant difference in the anxiety levels of the two groups. As hoped, the hypothesis was proven correct: Those subjects who watched television in the preoperative area had significantly lower levels of anxiety than those who did not. PMID- 1494992 TI - Is it a contact hour, a continuing education recognition point, or a continuing education unit? AB - Based on the content of this article, the reader should be able to: (1) differentiate between a contact hour, a continuing education recognition point, and a continuing education unit; (2) identify states that require mandatory continuing education for relicensure; and (3) define certification. PMID- 1494993 TI - When paradigms shift. AB - Paradigms are models that define boundaries and expected behavior. The health care paradigm is changing, and this shift from the old to the new model presents a real challenge to each manager who is trying to maintain a productive, cohesive staff. PMID- 1494994 TI - Responding to change in the decade of dilemma. AB - Virtually every politician seeking public office has proposed a national health care plan. Attempts to reduce the cost of health care have been less than successful. Indeed, cooperative action in dealing with health care problems is unlikely during this election year and probably for some time to come. In the following article the author shares some observations and predictions about the political, economic, social, and educational factors that will influence nursing practice in the 1990s, the decade of dilemma. PMID- 1494995 TI - Creating life strategies. PMID- 1494996 TI - Educating patients about missed medication doses. AB - 1. Missed-dose management, or the handling of a forgotten or omitted dose, is a necessary self-care skill for persistently and severely mentally ill patients. 2. A missed dose should generally be taken as soon as it is remembered, and doses should not be doubled. 3. Individual drug-specific instructions about missed-dose management are available for antipsychotics, antidyskinetics, and lithium. 4. Teaching patients about missed-dose management as well as the use of reminders to minimize missed doses are important nursing activities. PMID- 1494997 TI - A new nursing medium: computer networks for group intervention. AB - The PLWAs and the caregivers of persons with AD were similar in their adaptation to this new technology as a communication medium with nurses. Both groups availed themselves of the resources, both technological and personal, on the computer network. Although different in demographics, they also were similar in their ability to form and work in a traditional group structure. Nurses have historically intervened with groups, and this article demonstrates that nurses can intervene on a computer network with groups. Yalom's therapeutic factors exist in both non-face-to-face groups and traditional groups. The benefits of this technology to nurses are numerous: they can access clients in an efficient yet supportive manner; they can respond to multiple levels of need in multiple clients; and they can attend to emotional as well as more concrete needs of clients. The benefits to clients are also numerous: they can use the system at a time, frequency, and duration of their choice; they have the opportunity to be supported in self-care efforts versus being in a more dependent role; and they can engage in a normalization of their experiences. Computer networks can enhance nursing's ability to intervene with clients experiencing clinical problems. PMID- 1494998 TI - Therapeutic listening: developing the concept. AB - 1. Therapeutic listening is an art that all nurses, especially psychiatric nurses, must possess to be effective. Listening has been listed as the most effective therapeutic technique available. 2. Therapeutic listening is an interpersonal confirmation process, involving all the senses, in which the therapist attends with empathy to the client's verbal and nonverbal messages to facilitate the understanding, synthesis, and interpretation of the client's situation. 3. The therapeutic listening process includes maintaining eye contact; an attending posture; staying within conversational distance; responding with facial expressions, touch, gestures, and encouraging words; asking relevant questions; and interpreting and summarizing key points using specific words spoken by the client. PMID- 1495000 TI - The patient's perspective: prosumers. PMID- 1494999 TI - Pulling together: building a community debriefing team. AB - 1. Research shows that many emergency workers are affected physically and emotionally by critical incident stress. 2. Debriefings conducted by trained team members are an effective method to mitigate the impact of critical incident stress. A debriefing is a structured, time-limited group intervention. 3. Cooperation among community agencies is essential for the development and effective functioning of a critical incident stress debriefing team. 4. Several teams in Illinois have organized to form a Critical Incident Stress Debriefing Network. The Illinois network is part of an international organization composed of critical incident stress debriefing providers. PMID- 1495002 TI - What therapeutic and protective measures, as well as legal actions, can staff take when they are attacked by patients? PMID- 1495001 TI - Teaching hospitalized patients with serious, persistent mental illness. AB - 1. Although patient teaching is an important nursing function, minimal research was found related to education of patients with schizophrenia. Teaching psychiatric patients about illness, treatment, and rehabilitation has not received the same attention in psychiatric nursing as it has in other nursing specialties. 2. Eighty percent of the patients who participated in patient education classes would recommend the program to others. Treatment teams reported that some patients asked more questions about their treatment and became more active in ward groups following the classes. 3. The use of nurses as patient educators facilitates professional nursing practice and effectively ensures that patients' general physical health and psychiatric education needs are systematically addressed. PMID- 1495003 TI - Confidence builders: a self-esteem group at an inpatient psychiatric hospital. AB - 1. Many people with mental illness experience low self-esteem. They tend to minimize their own positive attributes, strengths, and abilities, making it difficult to accept positive feedback. 2. As an alternative to the one-to-one relationship, the Self-Esteem Group provides a situation in which self-esteem can be increased through constructive social interactions, trust, and support from group members. 3. Structured exercises, which encourage sharing and development of positive aspects of self, were completed by group members during each session. These exercises made it easier for group members to focus ideas, feelings, and experiences related to the topic for discussion. PMID- 1495004 TI - Effects of hyperthermia induced by microwave irradiation on brain development in mice. AB - Pregnant mice were exposed to 2.45 GHz of microwave radiation for 15 or 20 min on day 13 of gestation. The highest maternal core temperature during the exposure did not exceed 42.5 degrees C. Pregnant females also were immersed in hot water at 42 degrees C for 15 min to compare thermal effects on brain development. Animals were killed 9 hours after treatment, and the pyknotic cells in the ventricular zone of telencephalon were counted. The respective incidences of these cells in the groups exposed to microwaves for 15 and 20 min were 1.83% and 3.06%. Microwave radiation for 20 min had an effect that was comparable to that of immersion in 42 degrees C hot water for 15 min. In addition, some animals were examined on day 18 of gestation, and some of their offspring were examined at 6 weeks of age in an examination of long-term effects. Brain weight for the group exposed to microwaves for 20 min was significantly lower than for the control group, and the numerical density of the neurons in the cerebrum was higher. We concluded that microwave radiation at the dose tested mainly has a thermal effect. PMID- 1495005 TI - Rapid decrease in brain enkephalin content after low-dose whole-body X irradiation of the rat. AB - Methionine-enkephalin (ME) contents in the hypothalamus and other rat brain structures were measured immediately after 10 or 20 cGy whole-body X-irradiation. The ME contents of homogenates of the striatum, hypothalamus, midbrain + thalamus, hindbrain and pituitary were assayed radioimmunologically with 125I. The contents of all the structures, except the pituitary, decreased significantly after 20 cGy irradiation. The reduction in the hypothalamus was transient, ME content gradually recovering with time. These results suggest that the central nervous system of mammals is one of the most radiosensitive organs as judged by changes in stress-induced mediators such as ME. PMID- 1495006 TI - 3'-Spiro nucleosides, a new class of specific human immunodeficiency virus type 1 inhibitors: synthesis and antiviral activity of [2'-5'-bis-O-(tert butyldimethylsilyl)-beta-D-xylo- and -ribofuranose]-3'-spiro-5"-[4"-amino-1",2" oxathiole 2",2"-dioxide] (TSAO) pyrimidine nucleosides. AB - A series of 3'-spiro nucleosides have been synthesized and evaluated as anti-HIV 1 agents. Reaction of O-mesylcyanohydrins of furanos-3'-ulosyl nucleosides with base afforded [1-[2',5'-bis-O- (tert-butyldimethylsilyl)-beta-D-xylo- and ribofuranosyl]]-3'-spiro-5"- [4"-amino-1",2"-oxathiole 2",2"-dioxide] derivatives of thymine, uracil and 4-N-acetylcytosine 11 and 12. Desilylation of 11 and 12 gave the full deprotected 3'-spiro xylo- and ribofuranosyl nucleosides 13 and 14 or the partially 5'-O-deprotected-3'-spiro beta-D-xylo- and -ribo-nucleosides 15 and 16, or 2'-O-deprotected-3'-spiro beta-D-ribo-nucleoside 17. 2'-Deoxygenation of 17 afforded 2'-deoxy-3'-spiro beta-D-erythro-pentofuranosyl derivative 18. These 3'-spiro derivatives were evaluated for their anti-HIV-1 activity. All 3' spiro nucleosides having a xylo configuration did not show any anti-HIV-1 activity. 3'-Spiro ribo-nucleosides with none or only one silyl group at C-2' or C-5' or the 2'-deoxy derivative were also inactive at subtoxic concentrations. However, 3'-spiro ribo-nucleosides having two silyl groups at C-2' and C-5' were potent and selective inhibitors of HIV-1. None of the nucleoside analogues that showed anti-HIV-1 activity proved inhibitory to the replication of HIV-2 or SIV. PMID- 1495007 TI - Potential prodrug derivatives of 2',3'-didehydro-2',3'-dideoxynucleosides. Preparations and antiviral activities. AB - The preparations and antiviral activities of a series (4-17) of potential prodrug forms of the antivirals 2',3'-didehydro-2',3'-dideoxyadenosine (D4A) and 2',3' didehydro-2',3'-dideoxycytosine (D4C) are reported. The 5'-phenyl- and 5' methylphosphonates (4, 6, 8, and 10) and their phosphonothionate congeners (5, 7, 9, and 11), with the exception of 10, were inactive in vitro against HIV-1 and HIV-2. However, the 5'-phenyl, 5'-methyl, and 5'-(3'-thymidyl) phosphate diesters (12-17) demonstrated inhibition of the cytopathic effect of HIV-1 and HIV-2 (EC50 approximately 1-60 microM) and cytotoxicities (CC50 approximately 35-200 microM) at concentration levels comparable to those of their parent compounds, D4A and D4C. This strongly suggests that the diesters are hydrolyzed to the nucleosides D4A and D4C and/or their 5'-monophosphates. The facile hydrolysis of 12 and 13 to these products was demonstrated in a medium containing 10% fetal calf serum. The molecules can serve as ready prodrug sources of the free nucleosides and their 5' monophosphates. Evidently, the phosphonates and phosphonothionates are not similarly cleaved, nor are they phosphorylated to form antivirally active or cytotoxic products. The importance of intracellular formation of these products in the activation of 12-17 is less clear. Potential prodrugs 4-17 are all stable in aqueous solution for hours with the exception of 14. Conjugates 4-17 showed no activity against a series of DNA and RNA viruses. PMID- 1495008 TI - HIV-1 neutralization and tumor cell proliferation inhibition in vitro by simplified analogues of pyrido[4,3,2-mn]thiazolo[5,4-b]acridine marine alkaloids. AB - The antiviral/antitumor marine alkaloid dercitin was used as a lead compound to design analogues with anti-HIV and tumor inhibitory activities. Deletion of structural features contributing to cytotoxicity led to analogues with lowered T lymphocyte toxicity profiles. One compound, 5, induced complete protection against HIV-1 infectivity in vitro at 12.5 micrograms/mL (38 microM) without T cell toxicity up to 400 micrograms/mL. Compound 4 and 5 also inhibited the binding of HIV-1 to H-9 lymphocytes. These compounds may exert antiviral activity by a unique dual extracellular and intracellular mode of action--both preventing viral attachment to lymphocytes as well as intercalating with viral nucleic acid. Analogues with higher cytotoxicity such as 2 which retain the thiazole ring of the natural product proved effective in completely inhibiting the cell proliferation of breast, colon, and lung tumor cell lines at 1.5 microM concentration compared to a 70 microM dose level of 5-fluorouracil. A means of molecular separation of antiviral activity from cytotoxicity was thus achieved, and putative pharmacophores for antiviral and antitumor actions of the prototype molecule dercitin have been deduced. The 2-thio-9-acridinone derivatives 4 and 5 represent a new structural type exhibiting activity against HIV in vitro, serving as chemical leads in the design of anti-AIDS agents, while thiazolo[5,4 b]acridines such as 2 provide leads in the drug design of new antitumor agents. PMID- 1495009 TI - Quinoline antifolate thymidylate synthase inhibitors: variation of the C2- and C4 substituents. AB - Modifications to the bicyclic ring system of the potent thymidylate synthase (TS) inhibitor N-[4-[N-[(2-amino-3,4-dihydro-4-oxo-6- quinazolinyl)methyl]-N-prop-2 ynylamino]benzoyl]-L-glutamic acid (1, CB3717) have led to the synthesis of a series of quinoline antifolates bearing a variety of substituents at the C2 and C4 positions. In general the synthetic route involved the coupling of the appropriate diethyl N-[4-(prop-2-ynylamino)benzoyl]-L-glutamate with a disubstituted 6-(bromomethyl)quinoline followed by deprotection using mild alkali. The compounds were tested as inhibitors of partially purified L1210 TS. As a measure of cytotoxicity, the compounds were tested for their inhibition of the growth of L1210 cells in culture. Good enzyme inhibition and cytotoxicity were found for compounds containing chloro, amino, or methyl substituents at the C2 position with chloro or bromo substituents at C4. The effect on enzyme inhibition of varying the N10 substituent of 2h was similar to that observed in the quinazolinone-containing antifolates, indicating that the quinoline compounds may be interacting with the enzyme in a similar way to the quinazolinones. Also, the introduction of a 2'-fluoro substituent into the benzoyl ring of several of the quinoline antifolates led to an increase in both TS inhibition and the inhibition of L1210 cell growth. These data demonstrate that the N3-H of the pyrimidine ring of the quinazolinone antifolates is not required for binding to TS if appropriate substituents are placed at the C2 and C4 positions of the bicyclic ring system. PMID- 1495010 TI - Inhibitors of human renin with C-termini derived from amides and esters of alpha mercaptoalkanoic acids. AB - New transition-state analogues bearing C-termini derived from alpha mercaptoalkanoic acids, esters, and amides were prepared and evaluated as inhibitors of human renin. Addition of alpha-mercaptoalkanoate esters to a chiral Boc-amino epoxide intermediate led ultimately to the target [(2R,3S)-3-(BocPheHis amino)-4-cyclohexyl-2-hydroxy-1-butyl]thio derivatives. The corresponding sulfoxide and sulfone analogues were also investigated. Some of these derivatives, including one with a stable BocPhe replacement, were relatively potent inhibitors of human plasma renin, having IC50 values below 10 nM. When selected compounds were administered intravenously to sodium-deficient rhesus monkeys (Macaca mulatta) at 0.06-1 mg/kg, they reduced plasma renin activity by 87-94%. However, the accompanying drop in blood pressure was of short duration. PMID- 1495011 TI - New potent mitomycin derivatives: synthesis and antitumor activity of 7,7 (ethylenedioxy)mitomycins. AB - A series of 6,7-dihydro-7,7-(ethylenedioxy)mitomycins was synthesized and evaluated for antitumor and anticellular activities. These compounds were prepared by basic treatment of 7-methoxymitomycins with ethylene glycol, and were structurally novel mitomycin derivatives containing a masked quinone moiety. 5,6 Enol or 6-chloro derivatives of 6,7-dihydro-7,7-(ethylenedioxy)mitomycins were also prepared and the (allyloxy)carbonyl group at the aziridine nitrogen has proved to be an efficient protecting group in chemical modification of mitomycins. Most of these mitomycin derivatives displayed potent antitumor activity against P388 leukemia in mice and anticellular activity against HeLa S3 cells. PMID- 1495012 TI - Synthesis and anticonvulsant activity of enaminones. AB - A new series of novel enaminones has been synthesized from cyclic beta-dicarbonyl precursors which were condensed with morpholine, pyrrolidine, phenethylamine, hydrazines, substituted benzyl amines, and substituted anilines. These compounds were subsequently evaluated for anticonvulsant activity in a variety of anticonvulsant models by the National Institute of Neurological and Communicative Disorders and Stroke and in our laboratory. Several of these compounds exhibited potent anticonvulsant activity with a remarkable lack of neurotoxicity. The most active analog, methyl 4-[(p-chlorophenyl)amino]-6-methyl-2-oxo-cyclohex-3-en-1 oate++ + (27), was protective in the maximal electroshock (MES) seizure test in the rat with an oral ED50 of 5.8 mg/kg with no toxicity noted at doses up to 380 mg/kg, thus providing a protective index (TD50/ED50) of greater than 65.5. A similar protective index for 27 was noted upon intraperitoneal (ip) administration in mice. The anticonvulsant effect of 27 occurred within 15 min of administration and the compound remained active beyond 4 h. Compound 27 was also active in the rat corneal kindled model. The application of Free-Wilson analysis to structure-activity correlation in this series is discussed. PMID- 1495013 TI - N-methylated analogs of Ac[Nle28,31]CCK(26-33): synthesis, activity, and receptor selectivity. AB - A series of singularly N-methylated analogs of Ac[Nle28,31]CCK(26-33) were synthesized by the solid-phase methodology, and their biological activity was tested in three different in vitro bioassays. The bioassays employed were the guinea pig gallbladder (GPGB), stomach (GPS), and ileum (GPI). All N-methyl analogs were agonists in all three bioassays. N-Methylation at either N- or C terminals did not affect potency and selectivity, whereas N-methylation of internal residues [Nle28,(N-Me)Nle31]- and [Nle28,31,(N-Me)Trp30]CCK(26-33) in the sequence resulted in analogs which were 10-fold less potent than Ac[Nle28,31]CCK(26-33) in all three preparations. Different rank orders of potencies observed for [Nle28,31,Sar29]- and [Nle28,31,(N-Me)Asp32]CCK(26-33) analogs correspond to increased selectivity to either GPGB or GPS, respectively. We propose that systematic N-methylation of single amide bonds in a bioactive peptide should be conducted as an additional routine to probe structure-activity relationships. PMID- 1495014 TI - Stereoisomers of ketoconazole: preparation and biological activity. AB - The four stereoisomers of the antifungal agent ketoconazole (1) were prepared and evaluated for their selectivity in inhibiting a number of cytochrome P-450 enzymes. Large differences in selectivity among the isomers were observed for inhibition of the cytochromes P-450 involved in steroid biosynthesis, whereas little differences was observed for inhibition of those associated with hepatic drug metabolism. The cis-(2S,4R) isomer 2 was the most effective against rat lanosterol 14 alpha-demethylase, (2S,4R)-2 greater than (2R,4S)-4 much greater than (2R,4R)-3 = (2S,4S)-5, and progesterone 17 alpha,20-lyase, (2S,4R)-2 much greater than (2S,4S)-5 greater than (2R,4R)-3 = (2R,4S)-4, whereas the cis (2R,4S) isomer 4 was more effective against cholesterol 7 alpha-hydroxylase, (2R,4S)-4 greater than (2S,4S)-5 greater than (2R,4R)-3, greater than (2S,4R)-2, and the trans-(2S,4S) isomer 5 was the most effective against aromatase, (2S,4R) 5 much greater than (2R,4R)-3 = (2R,4S)-4 greater than (2S,4R)-2. The cis-(2S,4R) and trans-(2R,4R) isomers 2 and 3 are equipotent in inhibiting corticoid 11 beta hydroxylase and much more effective than their antipodes. Little selectivity was observed for inhibition of cholesterol side chain cleavage or xenobiotic hydroxylase. These data indicate that the affinity of azoles for cytochrome P-450 enzymes involved in steroid synthesis is highly dependent on the stereochemistry of the entire molecule, whereas binding to drug metabolizing enzymes is a less selective process. PMID- 1495015 TI - Preparation and structure-activity relationships of simplified analogues of the antifungal agent cilofungin: a total synthesis approach. AB - The echinocandins are a well-known class of lipopeptides characterized by their potent antifungal activity against Candida species. The mechanism of action of the echinocandins is generally thought to be the inhibition of beta-1,3-glucan synthesis, an important structural component in the cell wall of Candida species. Extensive structure-activity studies on the fatty acid side chain of echinocandin B (1) led to the preparation of the clinical candidate cilofungin (4). However, little is known about the cyclic peptide. We now report the preparation, by solid phase synthesis, of a series of simplified analogs of cilofungin in which the unusual amino acids found in the echinocandins were replaced with more readily accessible natural amino acids. The solid-phase approach to the total synthesis of these analogs allowed us to conveniently explore structural modifications that could not be accomplished by chemical modification of the natural product. The simplest analog 5 showed no biological activity. Structural complexity was then returned to the system in a systematic fashion so as to reapproach the original cilofungin structure. Antifungal activity and the inhibition of beta-1,3-glucan synthesis were monitored at each step of the process, thereby revealing the basic structure-activity relationships of the amino acids and the minimal structural requirements for biological activity in the echinocandin ring system. The results suggests that the 3-hydroxy-4-methylproline residue enhances activity but the L homotyrosine residue is crucial for both antifungal activity and the inhibition of beta-1,3-glucan synthesis. PMID- 1495016 TI - 2-Substituted 1-azabicycloalkanes, a new class of non-opiate antinociceptive agents. AB - 2-Substituted 1-azabicycloalkanes (3- and 5-aryloctahydroindolizines 2 and 11, 3 cyclohexyloctahydroindolizine 12, 4-aryloctahydroquinolizines 13, and 3 arylhexahydropyrrolizines 14) constitute a new class of non-opiate antinociceptive agents. These compounds demonstrated activity in the mouse abdominal constriction test and many were active in the mouse tail-flick test. trans-3-(2-Bromophenyl)octahydroindolizine (2a) did not bind to the opiate receptor nor did it affect arachidonate metabolism. 3-Aryloctahydroindolizines were prepared by catalytic hydrogenation of 1-aryl-3-(2-pyridinyl)-2-propen-1 ones. The X-ray crystal structure of (-)-2a was determined and absolute stereochemistry assigned as 3-R,8a-R. PMID- 1495017 TI - New antiinflammatory agents. 2. 5-Phenyl-3H-imidazo[4,5-c][1,8]naphthyridin-4(5H) ones: a new class of nonsteroidal antiinflammatory agents with potent activity like glucocorticoids. AB - We previously described new antiinflammatory agents, 4-hydroxy-2-oxo-1-phenyl-1H 1,8-naphthyridine-3-carboxamides 1. Further modification of the compounds bearing 1-phenyl-1,8-naphthyridin-2-one as a mother skeleton led to 5-phenylimidazo[4,5 c][1,8]naphthyridin-4(5H)-one derivatives 2 and 3. Regioselective synthesis of these compounds bearing a substituent at the 1- or 3-position was conducted according to the method shown in Schemes I and II. In this series of compounds, antiinflammatory activities were greatly influenced by the position and nature of substituents on imidazole. 3-Alkyl or 3-benzyl substitution result in the potent activity, but 1-substitution did not. Minor modification of the benzyl group reduced or eliminated the activity. Detailed examination of structure-activity relationships led to 3-benzyl-5-phenyl-3H-imidazo[4,5-c][1,8]naphthyridin-4(5H) one (22), which exhibited potent oral antiinflammatory activities in carrageenan , zymosan-, and reversed passive Arthus reaction-induced rat paw edemas (ED40 = 5.3, 0.37 mg/kg, ED50 = 0.47 mg/kg, respectively). This broad activity of 22 was like that of glucocorticoids. Compound 22 did not affect activities of CO and 5 LO enzymes and receptor binding of various ligands. As one of the mechanisms of action, induction of release of glucocorticoids was postulated. These results suggest that 22 represents a novel class of antiinflammatory agents. PMID- 1495018 TI - Quenched molecular dynamics simulations of tuftsin and proposed cyclic analogues. AB - We have used high-temperature quenched molecular dynamics calculations to investigate the conformational properties of tuftsin (Thr-Lys-Pro-Arg) in solution. Conformers obtained after quenching of the dynamical structures were sorted into families depending on their relative energies and backbone conformations. By examination of these families, several cyclic analogues of tuftsin were proposed and examined theoretically by further quenched dynamics simulations. Two of the four proposed analogues were found to adopt essentially identical conformations to that of linear tuftsin. It is suggested that these two derivatives (cyclo[Thr-Lys-Pro-Arg-Gly] and cyclo[Thr-Lys-Pro-Arg-Asp]) may be biologically active, and that the introduction of cyclic conformational constraints should help to reduce the entropic penalty to peptide binding. PMID- 1495019 TI - Nucleosides and nucleotides. 112. 2-(1-Hexyn-1-yl)adenosine-5'-uronamides: a new entry of selective A2 adenosine receptor agonists with potent antihypertensive activity. AB - Chemical modifications of the potent A2 adenosine receptor agonist 2-(1-hexyn-1 yl)adenosine (7, 2-HA) at the 5'-position have been carried out to find more potent and selective A2 agonists. These analogues were evaluated for adenosine A1 and A2 receptor binding affinity in rat brain tissues and antihypertensive effects in spontaneously hypertensive rats (SHR). Among the series of compounds, 2-(1-hexyn-1-yl)adenosine-5'-N-cyclopropyluronamide (16d) had the most potent affinity to the A2 receptor with a Ki of 2.6 nM, which is essentially the same as that of the parent agonist, 2-HA. However, the most selective agonist for the A2 receptor was 2-(1-hexyn-1-yl)adenosine-5'-N-methyluronamide (16b) with a Ki of 11 nM and a 162-fold selectivity. The N-alkyl substituents of 5'-uronamide derivatives did not seem to potentiate the A2 binding affinity but drastically reduced the A1 affinity compared with the parent 2-HA. Therefore, the A1/A2 selectivity was consequently increased. Other 5'-deoxy-5'-substituted derivatives of 2-HA such as the chloro (20), carboxamide (27, 28), sulfonamide (29), urea (30), and thiourea (22) analogues were also prepared. Among these nucleosides, no active compounds with potent or selective affinities to both receptors were found except 20. Although glycosyl conformations and sugar-puckering of these nucleosides were studied by 1H NMR spectroscopy, there were no positive correlations between active and inactive agonists. 2-(1-Hexyn-1-yl)adenosine-5' uronamide (16a) and 16d had a potent hypotensive effect at ED30 values of 0.18 and 0.17 micrograms/kg, respectively, upon iv administration to anesthetized SHR. PMID- 1495021 TI - Use of affinity capillary electrophoresis to measure binding constants of ligands to proteins. PMID- 1495020 TI - Probing the molecular basis of resistance to pyrimethamine by site-directed mutagenesis. PMID- 1495022 TI - Alkyl and aryl neoalkanamides: highly effective insect repellents. AB - Alkyl and aryl neoalkanamides with a total carbon number between 11 and 14, or within a molecular weight range between 185 and 227, were highly effective repellents of male German cockroaches, Blattella germanica (L.). Comparison with known repellents showed that members of this unique family of secondary amides are among the most effective and long-lasting repellents of cockroaches examined to date. In assays with females and nymphs of the German cockroach, male American cockroaches, Periplaneta americana (L.), and carpenter ant workers, Camponotus pennsylvanicus (De Geer) methyl neodecanamide, propyl neodecanamide, and methyl neotridecanamide were found highly repellent. Because of their broad spectrum of activity, longevity, and safety, these compounds, along with several other members of this family, have important applications as repellents of nuisance pests and of arthropods of public health importance. PMID- 1495023 TI - Mechanical control of greenhead flies (Diptera: Tabanidae) in a marsh environment. AB - The effectiveness of New Jersey box traps for the control of adult greenhead flies, Tabanus nigrovittatus, Macquart, T. conterminus Walker, was assessed at Wallops Island, Va. Trap shape and placement were tested. Shallow (0.45 m high) traps caught significantly fewer flies than cubic (0.60 m high) traps. Traps located in the inner two of four layers of traps caught fewer flies than traps in the outer layers. PMID- 1495024 TI - Carbon dioxide released from human skin: effect of temperature and insect repellents. AB - Measurement with an infrared analyzer of CO2 given off by the hands of human volunteers under laboratory conditions showed that they continuously produced CO2 at the rate of 1.0-1.8 ml/h. Increased production of CO2 was observed with increase in temperature for all subjects. Treatment of subjects with three insect repellents or ethanol resulted in a short-term drop in CO2 production, after which it returned to pretreatment levels. Olfactometer studies showed no correlation between the amount of CO2 produced by hands and the attractancy of the subjects to host-seeking female Ae. aegypti (L.). The supplemental addition of five times the amount of CO2 given off by the hands did not affect attractancy of subjects to mosquitoes. The amount of CO2 released by hands is negligible compared to ambient levels of 300 ppm, and it is unlikely to be attractive at this level of release by itself. PMID- 1495025 TI - Laboratory observations on mating and leklike aggregations in Lutzomyia longipalpis (Diptera: Psychodidae). AB - The mating behavior of the sand fly, Lutzomyia longipalpis, was studied under laboratory conditions. Male sand flies landed on the bodies of anesthetized mice, where they exhibited leklike displays such as wing fanning, parading, and aggression. Lek behavior was more frequent in older males, and dominance hierarchies were established. Male sand flies at leks copulated more frequently than male sand flies at other locations in the cage. Females mated by older males produced more eggs than did females mated by younger males; however, there was no difference in the number of larvae produced. PMID- 1495026 TI - Seasonal abundance of Lutzomyia shannoni (Diptera: Psychodidae) on Ossabaw Island, Georgia. AB - Population dynamics of Lutzomyia shannoni were monitored from April 1986 through December 1987 on Ossabaw Island, Ga. Most (99%) of the 19,788 adult sand flies were collected in light traps supplemented with dry ice; less than or equal to 1% were aspirated from diurnal resting sites. Adult sand flies first appeared in April and were followed by peaks of abundance during May 1986, and May and July 1987. Numbers of adults captured fell rapidly in October and November 1986 and in September and October 1987. No specimens were collected in December 1986 or in March, November, and December 1987. Light trap catch was affected positively by mean nightly air temperature and negatively by rainfall 14 d before collection, but not by wind speed or moon phase. Vesicular stomatitis viral activity, as measured by antibodies in feral and domestic swine, roughly corresponded to the seasonal appearance of adult L. shannoni during 1986 and 1987. Significantly more adults (72%) were collected in light traps at ground level (0.5m) than at heights of 4 and 8m. Most resting adults were collected from dark, moist tree holes and cavities of various hardwoods. PMID- 1495027 TI - Differential selection of malathion resistance in Anopheles culicifacies A and B (Diptera: Culicidae) in Haryana State, India. AB - In November 1989, for the first time after the introduction of malathion spray in 1982, increased densities of Anopheles culicifacies Giles s.l. were observed in Chhatera and Barota, two villages in Halalpur block in Sonepat District, Haryana State, India. In bioassay tests against the diagnostic dose of malathion (5% for 1 h), 41-47% of mosquitoes survived. An culicifacies populations in this area comprise two sibling species, A and B. Differential malathion resistance was observed; in species A it was 2-9% and in species B 62-66%. Likewise, species A was found to be more susceptible to DDT than was species B. The possible use of DDT spray to delay the onset of malathion resistance is discussed. PMID- 1495028 TI - Method to estimate relative transmission efficiencies of Anopheles species (Diptera: Culicidae) in human malaria transmission. AB - A mathematical expression was derived to estimate the relative malaria transmission efficiency of an anopheline species with respect to a standard well characterized species for which all vector parameters can be sufficiently determined. The method is particularly useful in situations where multiple anopheline species contribute to human malaria transmission and requires the estimation of the man-biting rate, the sporozoite rate, and the human malaria incidence. Under stable conditions of vector abundance, the average sporozoite rate in a species during a transmission season would by itself reflect its relative transmission efficiency. This "efficiency" then was used to calculate the "effective human-biting rate"; i.e., the human-biting rate of that species if it were to have ecological properties identical to those of the standard species. The standard well-characterized species then could be used with the effective human-biting rate of all species to quantify transmission, thus overcoming the need to measure vector parameters for all anopheline species contributing to transmission. An expression also was derived to calculate the relative contribution made by each species to malaria transmission. The usefulness of this method was illustrated using entomological and epidemiological data from Kataragama, Sri Lanka. PMID- 1495029 TI - Malaria transmission and vector biology on Sainte Marie Island, Madagascar. AB - A 17-mo longitudinal malaria survey (November 1988-March 1990) was carried out on Sainte Marie Island, an area on the east coast of Madagascar which is frequently visited by tourists. During 706 man-nights of capture, 46,401 mosquitoes belonging to 32 species were caught. Sporozoite rates were determined by ELISA and incriminated Anopheles gambiae Giles s.s., An. funestus Giles, and An. mascarensis De Meillon as vectors of malaria. An. gambiae, the main vector, was highly anthropophilic but largely exophilic. Transmission by this species occurred mainly from November to April; the overall circumsporozoite antigen positivity rate was 1.7%, with a maximum of 3.2% in March-April. The nightly peak of transmission occurred between midnight and 0400 hours. The annual inoculation rate was calculated to be 100 infective bites per human, of which 92 were of Plasmodium falciparum. An. funestus played a minor role in transmission. An. mascarensis, an anopheline endemic to Madagascar, was incriminated for the first time, as a malaria vector. The sporozoite rate in this species varied from 0.4 to 0.9% as shown by both ELISA and salivary gland dissections. Parasite indices in humans up to 20 yr of age fluctuated during the year from 64 to 80%. Bed nets are recommended for malaria protection for the local population and tourists. PMID- 1495030 TI - Diel patterns of cat flea (Siphonaptera: Pulicidae) egg and fecal deposition. AB - The quantity of eggs and feces deposited by replicate populations of cat fleas, Ctenocephalides felis (Bouche), from domestic house cats. Felis catus, were recorded at 1-h intervals over a 24-h period, in a photoperiod of 12:12 (L:D) (photophase, 0600-1800 hours [EST]). Egg production averaged 23.96 +/- 0.83 eggs per female per day and was greatest from 2400 to 0300 hours and lowest from 0700 to 0900 hours and from 1700 to 1900 hours. Daily fecal deposition was 0.77 +/- 0.03 mg feces per flea and did not vary significantly among hours. Flea eggs and adult feces were dropped continuously from infested cats, but significantly more eggs were shed at times of day when cats normally rest. More feces are concentrated in the small areas where cats rest than over the large areas they roam. Consequently, eggs and feces would not be deposited uniformly throughout the hosts home range, resulting in a clumped distribution of larval development sites at host resting areas. PMID- 1495031 TI - Sulfluramid resistance and vapor toxicity in field-collected German cockroaches (Dictyoptera: Blattellidae). AB - The toxicities of Raid Max Roach Bait (sulfluramid) and COMBAT Roach Control System (hydramethylnon) to susceptible and field-collected German cockroaches were examined. In all field-collected strains, a variable fraction of the population exhibited tolerance to Raid Max. In some strains, few males were killed in the first 5 d of exposure to Raid Max and some lived for up to 123 d when provided Raid Max only. Field-collected males that were given access to Raid Max for only 3 h following a 45-h starvation exhibited a 22-fold delay in mortality of 50% of the population compared with males that were continuously exposed to Raid Max. Males exposed to COMBAT for 3 h exhibited a similar pattern of mortality as males continuously exposed to this bait. Field-collected males provided COMBAT with or without rat chow exhibited identical patterns of mortality. However, males that were offered Raid Max along with rat chow exhibited significantly delayed mortality compared with males given Raid Max alone. A direct comparison of 1% hydramethylnon and sulfluramid, the active ingredients in COMBAT and Raid Max, respectively, in rat chow showed that physiological resistance to sulfluramid was involved; field-collected males consumed both baits equally on the first day, but whereas 100% of the males that were fed hydramethylnon-containing chow died within 5 d, only one of 25 males fed sulfluramid-baited rat chow died during this period, and males continued to consume large amounts of food. This suggested that, in the presence of alternate foods, the effective dose of sulfluramid was diminished, resulting in reduced mortality in males fed Raid Max. These results suggest that relatively high levels of resistance to sulfluramid are pervasive in field populations of the German cockroach. Experiments in which cockroaches were exposed to vapors of Raid Max or sulfluramid without direct contact showed that both acted as fumigants. The Raid Max bait remained lethal without direct contact for at least 170 d of continuous aeration in a fume hood. A headspace analysis revealed that sulfluramid was present in airborne collections of both technical sulfluramid and the Raid Max bait. PMID- 1495032 TI - Prevalence of Lyme borreliosis spirochetes in ixodid ticks of Japan, with special reference to a new potential vector, Ixodes ovatus (Acari: Ixodidae). AB - To determine the vectors of Lyme borreliosis in Japan, the ixodid ticks taken in Hokkaido, Fukushima, Nagano, Ehime, and Kochi Prefectures were examined individually for spirochetal infections by culturing their midgut tissues in BSK medium. The cultivable spirochetes identified as Borrelia burgdorferi were detected in Ixodes persulcatus Schulze adults (15.5% of 634), nymph (6.7% of 15) and Ixodes ovatus Neumann adult (9.6% of 188) from Hokkaido, I. ovatus adults (25.5% of 47) from Fukushima, and I. persulcatus adults (21.7% of 143) and I. ovatus adults (27.1% of 85) from Nagano. However, 72 Haemaphysalis spp. from Ehime and Kochi were free from spirochetal infection. I. persulcatus is a vector of Lyme borreliosis in the Far East, but in Japan, I. ovatus may also transmit the spirochetes to human and feral animals. PMID- 1495033 TI - Spectrophotometric method of quantifying adult cat flea (Siphonaptera: Pulicidae) feces. AB - Cat flea, Ctenocephalides felis felis (Bouche), feces are an essential part of larval nutrition under natural conditions. The mass values of adult flea feces can be measured by dissolving samples of flea feces in Drabkin's reagent, filtering, centrifuging, and measuring absorbance spectrophotometrically at 540 nm. Either flea feces or air-dried host blood can be used to generate the standard curve used to convert absorbance (optical density) values into mass values. Debris collected from flea-infested house cats averaged 23.02 mg debris per cat per h with an average of 10.41 mg flea feces per cat per h. Flea feces deposited in the environment serve as potential larval food. Adult flea feces comprised an average of 44.28% of the debris deposited from infested domestic house cats in this study. PMID- 1495034 TI - Trans-beta-farnesene as a feeding stimulant for the sand fly Lutzomyia longipalpis (Diptera: Psychodidae). AB - The aphid alarm pheromone, trans-beta-farnesene (TBF), was found to stimulate feeding in both male and female Lutzomyia longipalpis Lutz & Neiva. Four other structurally related compounds (farnesol; 808 farnesene; trans, trans-farnesyl acetate; farnesyl methyl ether) were slightly less stimulating to these insects. The effect of TBF varied with sand fly age and the concentration of the chemical used. In contrast, TBF did not stimulate feeding in either sex of four other sand fly species (L. shannoni Dyar, Phlebotomus papatasi (Scopoli), P. argentipes Annandale & Brunetti, P. perniciosus Newstead). TBF might be useful in enhancing L. longipalpis field collections or in developing a poison bait for the control of this species. PMID- 1495035 TI - Relationship between selected bacteria and the growth of immature house flies, Musca domestica, in an axenic test system. AB - To investigate the relationship between immature (maggot) house flies, Musca domestica, and bacteria, we compared the development of sterile first-instar maggots in each of 10 pure blood agar cultures of bacteria with growth on sterile blood agar (negative control) and on standard house fly rearing medium (positive control). Nine species of bacteria representing gram-negative and gram-positive rods, coccoid, and micrococcoid cell types supported house fly growth on blood agar. One bacterium, a strain of Bacillus cereus, inhibited maggot growth. The percent pupation for maggots that developed in the presence of eight of nine bacteria (range, 41-69%), was significantly greater than in sterile blood agar (0 5%), and did not differ significantly from maggot growth in the rearing medium (50-90%). Average pupal weight for maggots that developed on blood agar with bacteria ranged from 19 to 21 mg, a reflection of favorable growth conditions. Average pupal weight in the presence of three bacteria (19.9, 19.4, and 19.4 mg) was significantly less than respective pupal weights in house fly rearing medium (24.0, 22.3, and 22.1 mg), but there was no difference in average pupal weight with six bacteria and the house fly rearing medium. These findings illustrate that bacteria or their metabolic products are essential as nutrients for house fly maggot growth in blood agar; a wide variety of adventitious bacteria can contribute to the suitability of an organic substrate for maggot growth; and a naturally occurring isolate of B. cereus limits house fly maggot growth in blood agar, a relationship that has not been reported previously. PMID- 1495036 TI - Predation of Mansonia (Diptera: Culicidae) by native mosquitofish in southern Florida. AB - In experimental tanks and wading pools, the mosquitofish Gambusia holbrooki reduced densities of Mansonia larvae which, because of their attachment to the roots of aquatic plants, have been regarded previously as relatively impervious to predation. Exoskeletal remains of larval Mansonia were recovered from 43.5% of stomachs dissected from G. holbrooki, but not from Heterandria formosa (least killifish) collected from two undisturbed ponds covered with water lettuce (Pistia stratiotes L.). After 24 h in aquaria exposed to ambient light, predation by G. holbrooki reduced densities of Mansonia on water lettuce to one-third that of controls but in the dark, no significant differences were observed. In reduced light, densities of second- and fourth-instar Mansonia were reduced significantly after 1 wk of exposure to G. holbrooki. Video recordings of predation in aquaria revealed that G. holbrooki glean water lettuce roots to locate attached Mansonia and also capture free-swimming, dislodged larvae. PMID- 1495037 TI - Influence of photoperiod on egg production of cat fleas (Siphonaptera: Pulicidae) infesting cats. AB - Photoperiod affected the production of cat flea eggs by cats infested with cat flea, Ctenocephalides felis (Bouche). Cat flea eggs have a smooth chorion and do not adhere to the host. About 60% of fluorescing eggs placed in the pelage were recovered in collecting trays underneath the host in 2 h. An average of 87.7 eggs per cat was laid during the last 8 h of the scotophase compared with 49.9 and 59.1 eggs during the other 8-h periods. Significant variation in the number of eggs collected daily existed among the six cats. The activity budgets were similar for all the cats with the maximum sleep period during the photophase. The possible adaptive advantages of synchronizing egg production with photoperiod are discussed. PMID- 1495038 TI - Computer simulation of Babesia bovis (Babes) and B. bigemina (Smith & Kilborne) transmission by Boophilus cattle ticks (Acari: Ixodidae). AB - A computer model was developed to simulate the processes involved in transmission of the cattle fever parasites Babesia bovis (Babes) and Babesia bigemina (Smith & Kilborne) between cattle and Boophilus ticks. The model of Babesia transmission was combined with a dynamic life history model for population dynamics of the tick vectors, Boophilus microplus (Canestrini) and B. annulatus (Say). Epidemiological parameters and relationships in the model include the reduction in fecundity of infected ticks, rate of transovarial transmission, effect of cattle type and inoculation rate on infectivity of cattle, variation of infected cattle recovery rate with age of infection, inoculation rate, and species of parasite. Some parameters in the model were fitted by iterative simulations to produce realistic rates of Babesia infection in larval ticks. Comparisons of simulated and reported epidemiological data from one location in Australia indicated a reasonable level of validity for the model. Theoretical tick density thresholds for maintenance of Babesia in cattle and for inoculation of greater than or equal to 99.5% calves were determined by iterative simulations at 10 locations with B. microplus and six locations with B. annulatus. The model and transmission thresholds can serve as the basis for further simulation studies on strategies for control or eradication of babesiosis. PMID- 1495039 TI - Spatial analysis of the distribution of Ixodes dammini (Acari: Ixodidae) on white tailed deer in Ogle County, Illinois. AB - The pattern of infestations of Ixodes dammini on white-tailed deer in Ogle County in Illinois was studied through examinations of hunted deer from 1988 to 1990. The Illinois Geographic Information System mapped the spatial distribution of tick infestations on deer and related it to a known endemic focus for I. dammini and Borrelia burgdorferi (Castle Rock State Park), and to a major waterway (Rock River). Second-order neighborhood analysis was used to analyze the spatial distribution of deer around Castle Rock State Park. More than 25% of deer were infested. All deer were clustered around CRSP, but the clustering resulted mostly from clustering of infested deer around CRSP. CRSP is apparently the only important source of tick infestations in Ogle County. Clustering of infested deer did not change during the 3-yr study period. The dispersion pattern of ticks on deer was aggregated, with twice and three times as many ticks collected from bucks as from does and from fawns, respectively. More male ticks than female ticks were collected from infested deer. Of 59 ticks removed from harvested deer in 1990, 5.1% tested positive for B. burgdorferi. PMID- 1495040 TI - Laboratory and field evaluation of five repellents against the black flies Prosimulium mixtum and P. fuscum (Diptera: Simuliidae). AB - Deet (N,N-diethyl-3-methyl-benzamide), the lactone CIC-4 ([2-hydroxy-methyl cyclohexyl] acetic acid lactone), the USDA Proprietary Chemicals AI3-37220 (1- [3 cyclohexen-1-ylcarbonyl]-2-methylpiperidine) and ++[3-35765 (1-[3-cyclohexen-1 ylcarbonyl] piperidine), and the U.S. military extended duration repellent formulation (EDRF) of deet were evaluated for repellency in the laboratory and field against the black flies Prosimulium mixtum and P. fuscum. CIC-4, AI3-37220, and AI3-35765 were as effective as deet at repelling P. mixtum and P. fuscum in laboratory and field experiments. Only the EDRF provided significantly longer protection than the deet standard against these black flies in the field. PMID- 1495041 TI - Autogeny in three species of Triatominae: Rhodnius prolixus, Triatoma rubrovaria, and Triatoma infestans (Hemiptera: Reduviidae). AB - Autogeny, the capacity of a female to lay eggs without having ingested any blood meal in the adult stage, was studied in three species of Triatominae: Triatoma infestans, Triatoma rubrovaria, and Rhodnius prolixus. When nymphs of T. rubrovaria and R. prolixus were fed chicken blood, autogeny occurred frequently, even with only one meal. In T. infestans autogeny was frequent as well, but demanded at least two nymphal blood meals. Total number of autogenic eggs was positively correlated with the body weight of the adult female. We conclude, therefore, that autogeny is common in Triatominae. PMID- 1495042 TI - Aedes aegypti (Diptera: Culicidae) vision: spectral sensitivity and other perceptual parameters of the female eye. AB - From measurements of the mean ommatidial diameter (17.2 microns) and mean interommatidial angle (6.2 degrees) of the eye of female Ae. aegypti (L.), a minimum resolvable angle of 12.3 degrees and an eye parameter of 1.6 microns were calculated. The eye had relatively poor acuity but high overall sensitivity to light. Electroretinographs revealed spectral sensitivity ranging from ultraviolet (323 nm) to orange-red (621 nm), with sensitivity peaks in the ultraviolet (lambda max323-345 nm) and green (lambda max523 nm) wavelengths. The retina is capable of some wavelength discrimination. PMID- 1495043 TI - First report of Ixodes (Ixodes) minor Neumann (Acari: Ixodidae) from South Carolina. AB - Previous reports from the literature have indicated the northernmost range of extension of Ixodes minor Neumann to be southern Georgia with the greatest number of collections having been made in the coastal regions of that state. An unpublished record in the U.S. National Tick Collection indicated that I. minor had been collected as far north as South Island, Georgetown County, S.C., as early as 1933. I. minor was collected on three separate occasions in Charleston County, S.C., between October 1990 and February 1991, thus verifying the northern extension of this tick's range and the probable existence of a stable population on the coast of South Carolina. The roof rat (Rattus rattus) is reported for the first time serving as a host for I. minor. PMID- 1495044 TI - Description of six new species of the genus Leptotrombidium from Mindanao Island and notes on the medically important genera of chiggers (Acari: Trombiculidae) of the Philippine Islands. AB - In the Philippine Islands, the genus Leptotrombidium currently consists of members of the subgenera Leptotrombidium and Trombiculindus. The following species are described as new: L. (L.) macacaphilus, L. (L.) longimedian, L. (L.) mindanensis, L. (L.) urogale, L. (L.) oculascutum, L. (T.) roseannleilaniae. The distribution of, and comments on, the known vectors of Rickettsia tsutsugamushi, L. (L.) deliense and L. (L.) fletcheri and the previously reported L. (L.) sandfordi, are given. Information on species of the potential scrub itch genera Blankaartia, Eutrombicula, and Schoengastia and a key to the genera and species of medically important trombiculids is provided. PMID- 1495045 TI - Effect of egg mass age on subsequent oviposition by Simulium reptans (Diptera: Simuliidae). AB - The frequency distribution of Simulium reptans L. egg deposition on artificial substrates with different egg mass age characteristics showed there was a preference for substrates with 1-d-old egg masses present. The reason for this preference is not known, but it may involve an oviposition pheromone. PMID- 1495046 TI - Seasonal distribution and habitat selection by Aedes albopictus and Ae. riversi (Diptera: Culicidae) in northern Kyushu, Japan. AB - Temporal and spatial distribution of adult and larval Aedes albopictus (Skuse) and Aedes riversi Bohart & Ingram were studied on a small island and coastal area of northern Kyushu, Japan. Adults of Ae. albopictus attracted to human bait were distributed uniformly in an evergreen forest, a citrus orchard surrounded by forest, and an area disturbed by humans, whereas Ae. riversi was confined to evergreen forest and its adjacent area. Adults of both species occurred from May through October. Although Ae. riversi outnumbered Ae. albopictus early in the season, Ae. albopictus were much more abundant than Ae. riversi later in the season, with maximum abundance in July-September. Larval Ae. riversi occurred primarily in tree holes but also were found in bamboo stumps and artificial containers in forests. Despite the abundance of adult Ae. albopictus in the forest, larvae occurred in tree holes less frequently than Ae. riversi; it more frequently exploited bamboo stumps, stone vases, and discarded tires outside the forest. PMID- 1495047 TI - Tick (Acari: Ixodidae) attachment cement and salivary gland cells contain similar immunoreactive polypeptides. AB - A specific antiserum (12C) raised to a 90-kDa immunogenic component of salivary glands of the tick Rhipicephalus appendiculatus recognized similar 90-kDa polypeptides from salivary glands of the American dog tick, Dermacentor variabilis, and the lone star tick, Amblyomma americanum, as well as 70-kDa polypeptides in the cement of D. variabilis, A. americanum, and R. sanguineus (brown dog tick). The reduction in size of the polypeptide for these ticks suggests that it is modified in some way during or after secretion. Immunostaining of salivary glands of unfed- and partially-fed female D. variabilis localized an immunoreactive protein in the d- and e-cells of the type III acini. The quantity of label in granules of glands from unfed ticks was visibly greater than in the granules of glands from partially fed ticks, suggesting that this component is secreted within the first 2 d of feeding. Collectively, these data support the conclusion that a 90-kDa polypeptide of saliva is conserved among ixodid tick genera and is a component of the attachment cement. PMID- 1495048 TI - Feeding efficiency of larval Hyalomma truncatum (Acari: Ixodidae) on hosts previously exposed to ticks. AB - The effect of guinea pig response to feeding larval Hyalomma truncatum Koch ticks was studied by measuring the percentage of ticks engorging and molting, their engorged weight, and hemoglobin content. Four guinea pigs were infested with 100, 200, 400, and 1,000 larvae, respectively, on three occasions at 21-d intervals, followed by a fourth infestation with 500 larvae. During the second, third, and fourth infestations, significantly fewer ticks engorged on each guinea pig than during the first infestation. The greatest reduction in percentage molting occurred during the fourth infestation on the animal with successive exposure to 400 larvae; only 24% of the ticks that fed molted. Ticks with the lowest mean weight and hemoglobin content also engorged on this animal during the fourth infestation. Guinea pigs exposed to 200 and 400 H. truncatum larvae elicited the greatest change in feeding efficiency during the fourth infestation. However, these hosts had no effect on a single subsequent fifth infestation with Amblyomma cajennense (F.) nymphs, as greater than 95% successfully engorged. PMID- 1495049 TI - Rates of Borrelia burgdorferi infection in Ixodes dammini (Acari: Ixodidae) in southwestern Wisconsin. AB - Ixodes dammini Spielman, Clifford, Piesman & Corwin collected from a study site in southwestern Wisconsin were examined for Borrelia burgdorferi infection. Adult spirochete infection rates varied seasonally (38.1%, spring 1990; 60.3%, fall 1990; 41.2%, spring 1991) and were similar to or higher than rates reported in various studies from the northeastern United States. Statistical comparison of seasonal infection rates indicated a significant difference between the fall 1990 adult population and the subsequent overwintered population of the same cohort (spring 1991). Additionally, a significant decrease in the intensity of spirochete infection was observed in the overwintered adult sample. PMID- 1495050 TI - In vitro assay for the biosynthesis and metabolism of juvenile hormone by exposed corpora allata of Aedes aegypti (Diptera: Culicidae). AB - A technique has been developed to study JH III biosynthesis in vitro by removing the head and thorax of Aedes aegypti (L.) and exposing the corpora allata (CA). Exposed CA were incubated with [12-3H]methyl farnesoate, and the newly synthesized JH III and JH III metabolites were followed using C18 reversed-phase, high-performance liquid chromatography (HPLC) and preparative gas chromatography. The rate of synthesis of [12-3H]JH III by exposed CA from newly emerged adult Ae. aegypti was 23 fmol/CA/h. The rate of synthesis of [12-3H]JH III decreased 4-fold 3 d after adult eclosion and increased to 23 fmol/CA/h 5 h after the blood meal. Exposed CA of blood-fed and sugar-fed Ae. aegypti were also incubated with L [methyl-3H]methionine, and the rate of synthesis of JH III was studied. The rate of JH III biosynthesis increased immediately after the blood meal as was found with [12-3H]methyl farnesoate. The potential application of methyl farnesoate in monitoring the de novo synthesis of JH III in mosquitoes in vitro and in vivo is discussed. PMID- 1495051 TI - Sting morphology and frequency of sting autotomy among medically important vespids (Hymenoptera: Vespidae) and the honey bee (Hymenoptera: Apidae). AB - Data from clinical sting challenge investigations indicate that certain species of yellowjackets experience sting apparatus autotomy with surprisingly high frequency. However, a retrospective survey of vespid collectors strongly supports the supposition that the frequency of yellowjacket sting autotomy seen in clinical situations is not representative of the frequency experienced under field conditions. Examination by electron microscopy of the sting apparatuses of several vespid species and that of Apis mellifera L., the honey bee, revealed previously unreported structural variations between apid and vespid aculei which likely contribute to differences in sting autotomy rates observed between the honey bee and the social wasps. Specifically, when the lancets of a vespid aculeus are in a retracted position, the width of the smooth-edged stylet extends beyond the barbed edges of the lancets, forming a protective sheath. By contrast, all honey bee aculei possess stylets of insufficient width to shroud the barbs of retracted lancets, thus allowing the barbs to be completely exposed. Additionally, the dorsal surface of all vespid stylets are smooth in contrast to the dorsal surface of honey bee stylets, which support from one to three rows of paired barbs. The exposure of barbs on retracted honey bee lancets and the presence of additional barbs on the dorsal tip of the stylet would make withdrawal of a honey bee aculeus from a victim's flesh more difficult than withdrawal of a vespid aculeus, in which the barbs of retracted lancets are shielded and no dorsal barbs are present. PMID- 1495052 TI - Multiple transmission of Plasmodium gallinaceum (Eucoccida: Plasmodiidae) during serial probing by Aedes aegypti (Diptera: Culicidae) on several hosts. AB - Mosquitoes salivate before ingesting blood, and sporozoites are transmitted during this phase of feeding. In the laboratory, malaria-infected Aedes aegypti were allowed to probe on a series of three chicks during a 5-min period. Probing on each host was interrupted after 10 s. Our results demonstrate that up to three hosts can be serially infected with avian malaria during a 5-min period. PMID- 1495053 TI - Effects of temperature and humidity on ovipositional biology and egg development of the tropical horse tick, Dermacentor (Anocentor) nitens. AB - The ovipositional biology and egg development of the tropical horse tick, Dermacentor (Anocentor) nitens (Neumann), was observed at four temperatures (20, 25, 30, and 35 degrees C) and relative humidities (40, 61, 75, and 91% RH). Relative humidity had little effect on length of preoviposition and oviposition periods. With increased rearing temperatures, there was a decrease in both preoviposition and oviposition periods. Oviposition rate increased with temperature and was not affected by relative humidity. Instantaneous rates of oviposition were calculated for each temperature by fitting the data to the logistic growth function. High percentage egg hatch was observed in low saturation deficit environments, and decreased when saturation deficit was increased. PMID- 1495054 TI - Laboratory and field trials of permethrin-treated cotton used as nesting material to control fleas (Insecta: Siphonaptera) on cricetid rodents. AB - Upholstery cotton treated with four different concentrations (0.25-2.0%) (2,500 20,000 ppm) of an aqueous permethrin solution, used as nesting material by white mice, was laboratory-tested against the potential plague vectors Oropsylla montana (Baker), Thrassis bacchi (Rothschild), and Orchopeas howardi (Baker) and found highly effective (P less than 0.001) for 1 yr. Similarly treated cotton gauze was tested under ambient and 75% RH and was found to be highly effective (P less than 0.001) in both environments for 1 yr. A separate test determined that the LD50 of permethrin-treated cotton was less than 10 ppm. Cotton tested with 0.5% permethrin and distributed under field conditions to cricetid rodents for use as nesting material was found to be highly effective (P less than 0.001 as a pulicide for greater than 4 mo when tested during winter in Larimer County, Colo. Permethrin-treated cotton was less successful in controlling fleas on cricetid rodents during the summer months in a New Mexico hyperendemic plague area. PMID- 1495055 TI - Cyclical transmission of Plasmodium berghei (Coccidiida: plasmodiidae) by Anopheles omorii (Diptera: Culicidae). AB - Anopheles omorii, a tree-hole breeding anopheline collected in Japan, transmitted a rodent malaria, Plasmodium berghei ANKA strain, in the laboratory. Mice with 0.2-15% parasitemia, 0.01-1.5% gametocytemia, and 0.001-0.5% exflagellations were used as infective hosts. Oocyst numbers ranged from 2 to 171 (mean 44) on the midgut 8-16 d after the blood meal. Several to hundreds of sporozoites were detected in the salivary glands 14 d after feeding. The mosquitoes were infective to mice from 13 to 40 d after feeding. An. omorii occurs naturally at temperatures less than 25 degrees C and therefore is a suitable laboratory vector for the cyclic transmission of P. berghei, a malaria parasite that completes sporogony at 18-21 degrees C. PMID- 1495056 TI - Ammonia as an attractant for adult Hybomitra lasiophthalma (Diptera: Tabanidae). AB - Ammonia and carbon dioxide were evaluated as attractants in canopy traps for Hybomitra lasiophthalma (Macquart). Ammonia-baited traps collected 2.5 times as many flies as did unbaited traps (33.27 versus 12.93 per trap per day). Over 45 times as many flies were captured in carbon dioxide-baited traps as in unbaited traps (1,630.64 versus 35.82 per trap per day). Both ammonia and carbon dioxide are effective attractants for H. lasiophthalma. PMID- 1495057 TI - Occurrence of Ornithodoros kelleyi (Acari: Argasidae) in Kentucky. AB - A new distribution record is established for the tick Ornithodoros kelleyi Cooley & Kohls for Kentucky. Collections of this tick were associated with bat roosting sites in attics of houses. Scanning electron microscopy was used as an aid in distinguishing various taxonomic characteristics and morphological structures of O. kelleyi. PMID- 1495058 TI - Tick sweep: modification of the tick drag-flag method for sampling nymphs of the deer tick (Acari: Ixodidae). AB - We describe a version of the standard tick drag-flag modified for use in close growing and tangled vegetation, as well as under ornamental shrubbery and fallen branches. Two major features of the sweep are: (1) it allows the user to remain upright with the flag parallel to the ground, thus sampling effectively beneath low and fallen branches and around shrubs, as well as capturing host-seeking ticks in advance of the operator; and (2) the use of a flannel rubberized laminate fabric (crib sheet) for the flag that is snag-proof and highly durable in dense and thorny vegetation. In simultaneous 100-m samples, the sweep was as effective as the 1-m standard tick drag for capturing nymphs of the deer tick, Ixodes dammini Spielman, Clifford, Piesman & Corwin, where understory vegetation was sparse, but was twice as effective in dense vegetation, capturing significantly more I. dammini nymphs. The sweep also captured nymphs of the American dog tick, Dermacentor variabilis (Say); rabbit tick, Haemaphysalis leporispalustris (Packard); and lone star tick, Amblyomma americanum (L.). PMID- 1495060 TI - Sensitivity of a ribosomal RNA gene probe for identification of life stages of Anopheles arabiensis and An. gambiae (Diptera: Culicidae) using three storage methods. AB - Individual larvae, pupae, female adults, and adult body parts of Anopheles arabiensis Patton and An. gambiae Giles were stored for 1 mo either in isopropanol at room temperature, over a desiccant at room temperature, or at -70 degrees C. DNA was extracted, digested with EcoR1 restriction enzyme, subjected to electrophoresis in agarose gel, transferred to filters, then hybridized to a 32P-labeled rDNA probe. There was no difference among storage treatments in the proportion of correctly identified samples. First instars were not identifiable. Pupae and female adults were more likely to be identified than earlier life history stages. Nonetheless, the probe identified greater than 75% of second instars, 94% of third instars, and 74% of fourth instars. There were no differences between the species in the proportion of identifiable samples for any life history stage. PMID- 1495059 TI - Simultaneous field comparison of evening temporal distributions of nectar and blood feeding by Aedes vexans and Ae. trivittatus (Diptera: Culicidae) in Ohio. AB - Nectar- and blood-feeding time distributions of Aedes vexans (Meigen) and Aedes trivittatus (Coquillett) were determined from collections of mosquitoes attempting to feed on flowers and human bait during six nights in an Ohio field. Distributions of nectar and blood feeding were different in Ae. vexans on three of five nights when analyses were possible, and they were different in pooled Ae. trivittatus data. Higher proportions of blood feeders appeared in earlier time intervals, but both nectar and blood feeding had broadly overlapping peaks and distributions. These results suggest that the nectar- and blood-feeding rhythms are probably in phase in Ae. vexans females, and that possibly the earlier onset of blood feeding reflects a strategy taking advantage of blood when it is available. Male Ae. vexans had later peak nectar-feeding times than females. Nectar feeding in males may be delayed by mating activity early in the activity period. PMID- 1495061 TI - Volatile effects of insect growth regulators against the German cockroach (Dictyoptera: Blattellidae). AB - Third-instar German cockroach nymphs were held to maturity in continuous proximity to test surfaces treated with hydroprene and fenoxycarb, which they were unable to contact directly. Surfaces tested were unfinished plywood, fiberboard, vinyl tile (absorbent surfaces), glass, stainless steel, ceramic tile, and formica (nonabsorbent surfaces). Number of oothecae, percent egg hatch, and survival did not differ between any fenoxycarb treatment and the untreated controls, but there was significant wing twisting (76-94%) for all nonabsorbent surfaces. Number of oothecae was significantly lower and percent wing twisting was significantly higher for all hydroprene-treated surfaces with respect to the untreated controls, although survival was not affected. These effects were less pronounced for the nonabsorbent surfaces. These results indicate that hydroprene, but not fenoxycarb, has significant biological activity through volatile action when applied at current label rates. This activity is likely to have important consequences for control, especially for "crack and crevice" applications in confined spaces. PMID- 1495062 TI - Ornithodoros (Alectorobius) capensis Neumann (Acari: Ixodoidea: Argasidae), a parasite of seabirds, established along the southeastern seacoast of the United States. AB - Ornithodoros (Alectorobius) capensis Neumann, an ectoparasite of seabirds found circumglobally in the tropics and subtropics, has become established along the southeastern seacoast of the United States. The tick has been found feeding primarily on brown pelicans, Pelecanus occidentalis, but also has been found on the laughing gull, Larus atricilla, and the American oystercatcher, Haematopus palliatus. We report here the presence of O. (A.) capensis from New Hanover and Brunswick counties (near the mouth of the Cape Fear River) in North Carolina, to the Charleston Harbor area of South Carolina and thence south to Cumberland Island (a barrier island) in Camden County, Georgia, just north of the Florida state line. PMID- 1495063 TI - Effects of heat shock on the survival of transgenic Anopheles gambiae (Diptera: Culicidae) under antibiotic selection. AB - A gene for neomycin resistance linked to a Drosophila hsp 70 heat shock promoter was introduced into the germ line of Anopheles gambiae Giles. Effects of heat shock at 37 and 41 degrees C on the subsequent survival of the transgenic mosquito subjected to selection by the antibiotic G418 were studied. Heat shock did not enhance the survival of untransformed mosquitoes but greatly increased the survival of the transgenic mosquitoes. Survival after heat shock at 41 degrees C was greater than after heat shock at 37 degrees C. PMID- 1495064 TI - Release of Mesocyclops aspericornis (Copepoda) for control of larval Aedes polynesiensis (Diptera: Culicidae) in land crab burrows on an atoll of French Polynesia. AB - On Tereia Island, Rangiroa Atoll, 14,321 land crab burrows were treated with the copepod Mesocyclops aspericornis from January to June 1986, to control larvae of Aedes polynesiensis marks. In October 1987, the entire island of Tereia was retreated (17,300 burrows), and the neighboring island, Voisin, was left untreated as a control. From 5 to 15 mo after treatment, burrows with M. aspericornis contained an average of 2 Ae. polynesiensis immatures compared with 97 immatures from untreated burrows. Long-term larval control was successful in low-lying areas where burrows remained wet or were reflooded. Although there may have been other contributing factors, the major reason for lack of persistence of M. aspericornis in burrows over the entire island appeared to be poor resistance to desiccation. From all treated burrows in October 1987, M. aspericornis subsequently was found in 89.5, 39.1, and 24.1% of burrows sampled 5, 8, and 15 mo after treatment, respectively. The broad-scale results for Tereia indicated that there was no reduction of adult biting indices when compared with Voisin. Mark-release experiments on four occasions indicated that Ae. polynesiensis had a limited flight range and that the probability for interisland movement was low. PMID- 1495065 TI - Malaria transmission by Anopheles subpictus (Diptera: Culicidae) in a new irrigation project in Sri Lanka. AB - Indoor resting Anopheles subpictus in a new irrigation scheme in Sri Lanka were investigated during 1989-1990 for malaria infection by dissection and ELISA, and human feeding rates by ELISA analysis of blood meals. Indoor resting abundance was 22.3 females per house per 15-min catch in April-June 1989, 2.2 in November December 1989, and 7.5 in April-June 1990. ELISA-based malaria infection rates (Plasmodium vivax and P. falciparum combined) were 1.4% during April-June and 3.2% during November-December 1989, and 12.5% during April-June 1990. Dissection and ELISA confirmed the presence of oocysts and sporozoites of P. falciparum in 1990. Human blood was detected in 4.3, 0.8, and 5.2% of analyzed meals, respectively, during the three sampling periods. Estimates of the entomological inoculation rate (EIR) ranged from 0.00006 to 0.005 in different samples and vectorial capacity (VC) was 0.0005 for the 1990 sample. Thus, An. subpictus is incriminated as a vector of human malaria in Sri Lanka. PMID- 1495066 TI - Ecology of mosquitoes and St. Louis encephalitis virus in the Los Angeles Basin of California, 1987-1990. AB - St. Louis encephalitis (SLE) virus has become established in the Los Angeles Basin of California, where it most likely is maintained by horizontal transmission among Culex tarsalis Coquillet and passerine birds in park-riparian habitat. Viral transmission also was detected at low levels in residential habitat by the infrequent seroconversion of sentinel chickens. SLE virus activity was documented in all months except March and April. Cx. tarsalis was incriminated as the primary vector, based on elevated field infection rates (0.17 infected females per 1,000 tested), population abundance concomitant in time and space with increased SLE virus activity, vector competence, and vectorial capacity. Culex stigmatosoma Dyar also may be important in the horizontal maintenance of SLE virus because this species was an efficient laboratory vector, fed frequently on passeriform birds, and had field infection rates (0.15 females per 1,000) comparable with Cx. tarsalis. However, difficulty in trapping adult females precluded the assessment of Cx. stigmatosoma because abundance may have been underestimated and comparatively few females were tested for virus. Although Cx. quinquefasciatus Say was the most abundant species in residential habitats (greater than 85% of total catch at CO2 traps) where it occasionally fed on humans (0.6% of total tested), this species was considered to be of secondary importance because field infection rates were low (0.03 females per 1,000) and few females became infected and transmitted SLE virus in laboratory vector competence experiments. Although Culex erythrothorax Dyar fed on humans in marsh habitat (5% of total tested), this species infrequently fed on birds (12%) and was refractory to SLE virus infection in vector competence experiments; therefore, it was not considered a vector of SLE virus. Future SLE virus surveillance and mosquito control programs should be directed toward Cx. tarsalis populations. PMID- 1495067 TI - Laboratory evaluation of Brazilian Mesocyclops (Copepoda: Cyclopidae) for mosquito control. AB - In laboratory tests, four different strains of Mesocyclops aspericornis (Daday) collected in or near Fortaleza, Brazil, showed potential as biological control agents of Aedes aegypti (L.) mosquito larvae but were not as effective against Anopheles or Culex. In contrast, the larger M. longisetus (Thiebaud), collected at Fortaleza, killed 100% of Ae. aegypti and Anopheles farauti (Laveran) (No. 1) at larval densities of 200/liter and Culex quinquefasciatus (Say) at 25/liter. In cage simulations with Ae. aegypti and Mesocyclops, both copepod species eliminated all immatures in earthenware pots by week 3. Owing to the lack of replacement, all Ae. aegypti adults subsequently died by week 8 or 9. Although both M. longisetus and M. aspericornis showed maximum reproductive potential at 25 degrees C, breeding occurred from 20 to 35 degrees C. Based on these laboratory evaluations, M. longisetus has been selected for field trials in rural villages in Ceara to control Ae. aegypti. PMID- 1495068 TI - Oviposition habits of Simulium kawamurae (Diptera: Simuliidae), with reference to seasonal changes in body size and fecundity. AB - Oviposition habits and seasonal changes in wing length, head width, and number of ovarioles of Simulium kawamurae Matsumura were investigated in Kyushu Island, Japan. Gravid flies swarmed over turbulent water and laid eggs on rock surfaces in the splash zone. Large, irregular egg masses often resulted from the mass oviposition by many females within the same small area. Oviposition occurred at dusk during spring-summer, shifting to earlier periods during autumn-winter. Fecundity increased linearly as a function of body size (i.e., both with the cube of wing length and of head width, showing a better fit with the latter). Spring flies had a larger mean body size and fecundity than both summer and autumn flies. Winter flies had wings as long as spring flies, but their head widths and fecundity were comparable to summer-autumn individuals. This indicated seasonal variation in the relative proportion of body structures. PMID- 1495069 TI - Development and evaluation of dot-immunobinding assay for detection of scrub typhus infection in Leptotrombidium fletcheri (Acari: Trombiculidae). AB - A dot-immunobinding assay (DIBA) was compared with a direct fluorescent antibody technique (DFAT) for the detection of Rickettsia tsutsugamushi infection in Leptotrombidium fletcheri (Womersley & Heaslip). Laboratory colonies of infected and noninfected chiggers were examined. The relative proportions of positive, negative, and indeterminate results were significantly different between DIBA and DFAT for infected but not for noninfected chiggers. DIBA was more sensitive and had a better negative predictive value and a lower false negative percentage than DFAT. It was concluded that DIBA is a suitable alternative to DFAT for detecting scrub typhus infection in chiggers. PMID- 1495070 TI - Infectivity of entomopathogenic nematodes (Steinernematidae and Heterorhabditidae) to female ticks of Boophilus annulatus (Arachnida: Ixodidae). AB - Exposing Boophilus annulatus (Say) to different concentrations of Steinernema carpocapsae (Filipjev) infective juveniles in petri dishes (50-10,000 nematodes per dish) resulted in high mortality (greater than 90%) at nematode concentrations as low as 500 nematodes per dish within 8 d. At a concentration of 10,000 nematodes per dish, 100% of the ticks died within 2 d after infestation. After exposure to 500 nematodes per dish, complete mortality was achieved with the Heterorhabditis bacteriophora strain 'HP88' within 4 d. During the same period, only 15 and 40% mortality were recorded with the 'Mexican' and 'All' strains of S. carpocapsae, respectively. In a lethal dose analysis, S. carpocapsae strain 'DT' was the most infective strain with the lowest LD50 and LD90 values (15 and 165 infective juveniles per tick, respectively). The 'All' strain of S. carpocapsae was the least infective of the four strains tested, with LD50 and LD90 values of 372 and 9,251 infective juveniles/tick, respectively. Optimal temperature for tick control by the nematodes was between 22 and 26 degrees C. Mortality rate was reduced at 18 and 30 degrees C. The susceptibility of fully engorged ticks was not influenced by the weight of the replete females. Nematode infection did not have an adverse effect on egg laying by surviving ticks. PMID- 1495071 TI - In vivo and in vitro biosynthesis and metabolism of methyl farnesoate, juvenile hormone III, and juvenile hormone III acid in the mosquito Aedes aegypti. AB - Biosynthesis and metabolism of juvenile hormone (JH) III in vivo and in vitro were studied in female Aedes aegypti (L.). [12-3H]Methyl farnesoate was used to follow the synthesis and [12-3H]-(10R)-JH III to study metabolism. The rate of biosynthesis of [12-3H]JH III in vivo after adult eclosion increased from 9 fmol/h per female at 1 h to 22 fmol/h per female at day 6. The rate of biosynthesis by exposed corpora allata (CA) in vitro was 23 fmol/h per CA during the 1st d after adult eclosion, then dropped to 4.8 fmol/h per CA on day 3, then increased again to a constant level of synthesis (12 fmol/h per CA) at days 4-6. Immediately after blood feeding, the rate of synthesis of [12-3H]JH III in vivo and in vitro increased to 27 fmol/h per female and to 23 fmol/h per CA, respectively. The rate of synthesis then decreased in vivo to 12 fmol/h per female at 4 h and in vitro to 6 fmol/h per CA 10 h after the blood meal. After this decrease, the rate of synthesis of [12-3H]JH III increased again reaching a peak of 25 fmol/h per female at 48-96 h in vivo and 12 fmol/h per CA at 72 h in vitro. These results indicated that the CA of sugar-fed and blood-fed female A. aegypti synthesized JH III in vivo and in vitro from [12-3H]methyl farnesoate. When [12-3H]-(10R)-JH III metabolism was followed in vivo in female A. aegypti, the ratio between JH III diol acid:JH III acid:JH III diol was 17:4:1, indicating that JH III was first hydrolyzed by JH III esterase to the acid form, then hydrated to the diol acid by JH III epoxide hydrase. Females treated with [12 3H]JH III acid converted 46% of the JH III acid in 60 min to the diol acid. These results indicated that the enzyme epoxide hydrase acted on JH III acid 17 times faster than JH III. PMID- 1495072 TI - Isolation of Borrelia burgdorferi (Spirochaetales: Spirochaetaceae) from Ixodes scapularis and Dermacentor albipictus ticks (Acari: Ixodidae) in Oklahoma. AB - Borrelia burgdorferi was isolated from Ixodes scapularis Say and Dermacentor albipictus Packard that were removed as partially fed adults from white-tailed deer, Odocoileus virginianus Zimmermann, in Oklahoma. Isolation in media was accomplished only after homogenates of pooled field-collected ticks were inoculated into laboratory-reared Peromyscus leucopus and reisolated from the urinary bladder into BSK II media. Both isolates were confirmed by western blot analysis and reactivity with monoclonal antibody H5332. These are the first reported isolates of B. burgdorferi from Oklahoma from these two tick species and are the first isolates from ticks from the south-central United States that were infective for laboratory-reared P. leucopus. PMID- 1495073 TI - Field evaluation of two formulations of cyfluthrin for control of Ixodes dammini and Amblyomma americanum (Acari: Ixodidae). AB - Liquid or granular cyfluthrin was applied in the spring and fall to different test plots at a rate of 0.41 (AI) kg/ha to control Ixodes dammini Spielman, Clifford, Piesman & Corwin and Amblyomma americanum (L.). Spring application of liquid cyfluthrin showed the most significant decreases of both species. I. dammini nymphs were reduced 97% at 10 d, 100% at 2 mo, and 100% at 1 yr; and A. americanum adults and nymphs were reduced 91-93% at 10 d and 100% at 2 mo posttreatment. Granular cyfluthrin applied in the spring gave 97 and 87% control of nymphal I. dammini 10 d and 2 mo posttreatment, respectively. PMID- 1495074 TI - Effect of the repellent deet on the antennal chemoreceptors for oviposition in Aedes aegypti (Diptera: Culicidae). AB - The insect repellent, N,N-diethyl-m-toluamide (deet), interferes with detection of the host attractant, lactic acid (LA), by LA-excited neurons on the antennae of female Aedes aegypti (L.) mosquitoes. In the current laboratory behavioral experiment, the attraction of gravid female mosquitoes to a source of ethyl propionate, an oviposition attractant, was reduced by a factor of two when deet was present. Similarly, when deet was presented together with ethyl propionate in electrophysiological experiments, sensitivity of the neural response to ethyl propionate was depressed in a transient, dose-dependent manner that could account for the reduction in behavioral attraction of gravid females to ethyl propionate. Electrophysiologically, the sensitivity of oviposition attractant receptors to ethyl propionate on gravid females was not different from that on nongravid host seeking females. The similarity between the depression of sensitivity of the oviposition attractant-sensitive neurons induced by deet and that observed in the host attractant-sensitive neurons suggest a common mode of action of deet on peripheral chemoreceptor neurons that mediate these behaviors. PMID- 1495075 TI - Experimental transmission of African swine fever virus by the soft tick Ornithodoros (Pavlovskyella) marocanus (Acari: Ixodoidea: Argasidae). AB - A total of 1,600 Ornithodoros (Pavlovskyella) marcocanus larvae were fed on a pig with a viremia of 10(7.4) HAd50/ml of African swine fever virus (ASFV). Infected larvae were sampled daily for 15 d, and nymphs were sampled at least once per instar until they became adults. Initial titers of 10(4.48) HAd50 per larva declined to 10(4.04) within 2 d. Larval titers reached a maximum of 10(6.0) HAd50 per larva 10 d after the infective blood meal. Nymphs of each instar were fed on a susceptible pig and in each case transmitted ASFV by bite. Virus titers for first to fourth instars ranged from 10(4.61) to 10(3.34) HAd50 per nymph. Transstadial survival occurred in subsequent first, second, third, and fourth instars with an 89% survival rate over 250 d. Approximately 30% of adult ticks that were infected as larvae remained infected and transmitted ASFV to susceptible pigs 588 d later. In addition, ASFV was recovered from the same adult ticks 655 d after the infective blood meal. PMID- 1495076 TI - Persistence of Anaplasma marginale (Rickettsiales: Anaplasmataceae) in male Dermacentor andersoni (Acari: Ixodidae) transferred successively from infected to susceptible calves. AB - The persistence of Anaplasma marginale Theiler in male Dermacentor andersoni Stiles ticks exposed to the organism as adults was studied as the ticks were successively transferred to five susceptible calves. All calves fed upon by these ticks rapidly developed clinical anaplasmosis; incubation periods of infection ranged from 19 to 26 d and did not change significantly with successive feedings. Development of A. marginale in tick midgut and salivary glands was followed daily during tick feeding (total, 35 d) with light microscopy and DNA hybridization. With microscopy, A. marginale colonies persisted in midgut cells throughout the experiment. Large colonies were observed in gut muscle cells on days 8 through 35 and were the predominant infected cell type during this part of feeding. Colonies were seen in salivary gland acini from day 2 throughout the 35-d experiment. The DNA probe confirmed the presence of Anaplasma DNA in midgut and salivary glands throughout the experiment. Quantitative estimates of infection intensity in tissues of individual ticks approximated 10(7) initial body equivalents, confirming heavy infections. A marginale in midgut tissues decreased with feeding time, whereas the estimated number of organisms in salivary glands remained constant. These data demonstrate that D. andersoni males are efficient vectors of A. marginale and may be potential reservoirs of infection for ruminants for extended periods. PMID- 1495077 TI - Cluster of tick-borne infections at Fort Chaffee, Arkansas: Rickettsiae and Borrelia burgdorferi in ixodid ticks. AB - Human intrusion into pristine habitats increases the likelihood of acquiring infectious agents from potentially infective ticks. As part of a larger human serological investigation into tick-borne illnesses, 3,000 ixodid ticks were collected during May, August, and November 1990 at Fort Chaffee, Arkansas. Ticks were examined to determine whether they harbor rickettsiae, ehrlichiae, and Borrelia burgdorferi, and to assess relationship to human exposure to tick-borne infections at Fort Chaffee, Ark. The overall tick infection rates with SFG rickettsiae, B. burgdorferi, and ehrlichiae were 4.8, 0.1, and 0.3%, respectively. PMID- 1495078 TI - Attempted transmission of Borrelia burgdorferi (Spirochaetales: Spirochaetaceae) (JDI strain) by Ixodes scapularis (Acari: Ixodidae), Dermacentor variabilis, and Amblyomma americanum. AB - Laboratory-reared Ixodes scapularis Say, Amblyomma americanum (L.), and Dermacentor variabilis (Say) were fed on New Zealand white rabbits experimentally infected with Borrelia burgdorferi (JDI strain). At repletion, spirochetes could be detected by dark-field microscopy only in I. scapularis. Acquisition rates were 18 and 21%. When previously exposed nymphs of each species were fed on susceptible rabbits, I. scapularis was the only tick of the three species that transmitted B. burgdorferi. When a single rabbit was experimentally infected with B. burgdorferi and infested at 7-d intervals with I. scapularis, A. americanum, D. variabilis, and a second time with I. scapularis, B. burgdorferi was detected again only in cultures from the two groups of I. scapularis. When molted nymphs from each tick species were allowed to feed on susceptible rabbits, spirochetes again were isolated only at necropsy from the rabbits on which the two groups of I. scapularis fed. PMID- 1495079 TI - Age structure of horn fly (Diptera: Muscidae) populations estimated by pterin concentrations. AB - Pterins accumulate in the head capsules of horn flies, Haematobia irritans irritans (L.), as a linear function of time and temperature. Pterin concentrations were used to estimate chronological ages and to establish correlations between chronological age and ovarian development and reproductive success in 12 horn fly populations in 1988 and 1989. Male ages were estimated spectrofluorometrically. There were statistically significant differences between years in population age structure measured by pterins. Survival rates estimated from pterin concentration distributions were consistent with a one-parameter exponential model with constant survival rate. Mean daily survival rates were 0.81 for females and 0.84 for males in 1988 and 0.66 and 0.75 in 1989. Mean lifetime egg production was approximately 26 eggs per female in 1988 and 8 in 1989. Female reproductive success was close to the maximum possible, i.e., there were no net delays in oviposition. Analysis of gonotrophic age distributions provided survival estimates that suggested an increasing risk of mortality with age or age-related biases in sampling. PMID- 1495080 TI - Test for assortative mating between Boophilus microplus and Boophilus annulatus (Acari: Ixodidae). AB - The closely related cattle ticks, Boophilus microplus (Canestrini) and B. annulatus (Say), were tested for possible assortative mating under conditions designed to mimic those in the field. Patterns in the numbers of the four possible types of matings were generally indicative of a preference for conspecific mates in both species. There were significantly more conspecific and fewer interspecific matings than would be predicted from the observed frequencies of males and females among the two species had they mated at random. PMID- 1495081 TI - Autogeny in the neotropical sand fly Lutzomyia lichyi (Diptera: Psychodidae) from Colombia. AB - Host-seeking females of the anthropophilic sand fly, Lutzomyia lichyi (Floch & Abonnenc), collected in Valle, Colombia, were invariably parous. All progeny of these insects reared in the laboratory were autogenous for the first ovarian cycle, producing fertile eggs without a blood meal. The importance of autogeny in Leishmania transmission is discussed briefly. PMID- 1495082 TI - Evidence of seasonal eggs in Anopheles punctipennis (Diptera: Culicidae). AB - Anopheles punctipennis (Say), collected in October from resting sites in Illinois, deposited two morphologically distinct types of egg batches. One type was similar to the seasonal "winter" egg of Anopheles walkeri Theobald, with an extensive exochorion that covered all except the tip of the egg. Laboratory rearing of isofemale lines, under two different light-dark and temperature cycles, demonstrated that both types of eggs were intraspecific variants. F1 females from all "winter" egg batches deposited only normal eggs when reared under a 12:12 (L:D) cycle and at 25 degrees C. Most An. punctipennis reared under a 8:16 (L:D) cycle with variable temperature exhibited gonotrophic dissociation or accumulated fat body. PMID- 1495083 TI - Susceptibility of Periplaneta brunnea (Dictyoptera: Blattidae) to the nematode Steinernema carpocapsae (Rhabditida: Steinernematidae). AB - Brown cockroaches, Periplaneta brunnea Burmeister, were exposed to increasing population densities of the entomogenous nematode, Steinernema carpocapsae (Weiser), All Strains. A total of 160 adult cockroaches were used, 40 for each of four treatments: 0, 3,000, 30,000, and 300,000 infective juveniles added to 50 cm3 of sand. Population densities of 30,000 and 300,000 infective juveniles per 50 cm3 sand were the most effective treatments, killing 55% of the P. brunnea. The highest population density of nematodes, 300,000 infective juveniles per 50 cm3 sand, killed 93% of the P. brunnea, and produced a more rapid mortality when compared with other population densities. PMID- 1495084 TI - New host of Ixodes dentatus (Acari: Ixodidae), and first record in Tennessee. AB - Two specimens of Ixodes dentatus Marx were found in southwestern Tennessee in Shelby County during a 14-mo tick survey. This was the first record for this tick in Tennessee. An adult female was found on a dry ice trap and one larva was found on a live-trapped Peromyscus leucopus, the first time this tick has been reported from P. leucopus. This may be another combination of vector and host in the ecology and transmission of B. burgdorferi in the wild. PMID- 1495085 TI - Third-year evaluation of host-targeted permethrin for the control of Ixodes dammini (Acari: Ixodidae) in southeastern Connecticut. AB - The impact of commercially available permethrin-treated cotton balls targeted at Ixodes dammini Spielman, Clifford, Piesman & Corwin on white-footed mice, Peromyscus leucopus, was evaluated for a third year at five residential sites in south-central Connecticut. Each site had been treated twice each year from 1989 through 1991 with sufficient product to treat 0.4 ha of mouse habitat, and results were compared with five untreated sites. There were no significant differences in the number of host-seeking nymphs or adults of I. dammini, the vector of the Lyme disease spirochete, Borrelia burgdorferi, in 1991 between the treated and untreated sites. The rate of infection in host-seeking nymphs by B. burgdorferi at the treated sites (15.3% of 600) was comparable with that at the untreated sites (16.5% of 454). Only 16.3% of 86 P. leucopus captured at the treated sites were infested with I. dammini subadults compared with 66.9% of 118 from the mice at the untreated sites. The impact of permethrin-treated cotton during the third year of treatment was similar to that observed for the first 2 yr and did not reduce the risk of exposure to spirochete-infected, host-seeking nymphs and adults of I. dammini. PMID- 1495088 TI - Intracellular ion concentrations in the isolated frog skin epithelium: evidence for different types of mitochondria-rich cells. AB - Intracellular ion concentrations were determined in split skins of Rana pipiens using the technique of electron microprobe analysis. Under control conditions, principal cells and mitochondria-rich cells (MR cells) had a similar intracellular ion composition, only the Cl concentration in MR cells was significantly lower. Inhibition of transepithelial Na transport by low concentrations of ouabain (2 x 10(-6) M, inner bath) resulted in a Na concentration increase of principal cells from 10.9 to 54.3 mmol/kg wet wt. The increase was completely abolished by simultaneous application of amiloride (10( 4) M, outer bath). Amiloride alone resulted in a significant decrease of the Na concentration to 6.1 mmol/kg. w.w. Among MR cells, two different groups of cells could be distinguished; cells that showed a Na increase after ouabain which was even larger than that in principal cells and cells that did not respond to ouabain. In about half of all ouabain-sensitive MR cells the Na increase could be prevented by amiloride. According to these results, a subpopulation of MR cells displays the transport characteristics expected for a transepithelial Na transport compartment, an apical amiloride-sensitive Na influx and a basal ouabain-inhibitable Na efflux. Given the small number of cells, however, it is unlikely that this subtype of MR cells contributes significantly to the overall rate of transepithelial Na transport. PMID- 1495087 TI - Stretch activation of the Aplysia S-channel. AB - The S-channel, a receptor-mediated K+ channel of Aplysia sensory neurons which functions in neuromodulation, bears a strong resemblance to the ubiquitous stretch-activated channels of snail neurons. Snail neuron stretch channels are stretch sensitive only in the patch, not at the macroscopic level, a situation which leaves open the question of their physiological role. If S-channels resemble snail stretch channels because both belong to the same general class of channels, the S-channel, too, should display stretch sensitivity in the patch. We show, using single-channel recording, that the S-channel can be activated by stretch. Furthermore, we show that Aplysia neurons in general have stretch activated K+ channels. We suggest that the stretch-sensitive K+ channels of molluscan neurons and other preparations (e.g., Drosophila muscle, snail heart) are S-like channels, i.e., receptor-mediated channels which adventitiously exhibit mechanosensitivity in the patch. PMID- 1495086 TI - Possible mechanism of ciliary stimulation by extracellular ATP: involvement of calcium-dependent potassium channels and exogenous Ca2+. AB - Ciliary motility was examined optically in tissue cultures from frog palate epithelium and frog's esophagus as a function of extracellular concentration of adenosine 5'-triphosphate (ATP) and related compounds. The addition of micromolar concentration of ATP caused a strong enhancement of frequency and wave velocity in the direction of the effective stroke. Since adenosine 5'-[beta,gamma imido] triphosphate (AMP-PNP), a nonhydrolyzable analog of ATP, produces the same effects, ATP hydrolysis is not required. The overall potency is ATP approximately equal to AMP-PNP greater than ADP much greater than adenosine greater than AMP. It is suggested that both the phosphate and the base moieties are involved in ATP binding. The enhancement of ciliary activity by extracellular ATP is dependent on the presence of extracellular Ca2+, which can be replaced by extracellular Mg2+. The effect of a number of potent inhibitors of the voltage-gated calcium channels on the stimulation of ciliary activity by ATP were examined. No effect was detected in the concentration range within which these agents are specific. On the other hand, quinidine, a potent inhibitor of K+ (calcium-dependent) channels, inhibits the effect of ATP. The following model is suggested: exogenous ATP interacts with a membrane receptor in the presence of Ca2+, a cascade of events occurs which mobilizes intracellular calcium, thereby increasing the cytosolic free Ca2+ concentration which consequently opens the calcium-activated K+ channels, which then leads to a change in membrane potential. The ciliary response to these changes is the enhancement of ciliary activity. PMID- 1495089 TI - The application of electron spectroscopic imaging for quantification of the area fractions of calcium-containing precipitates in nervous tissue. AB - Energy-filtering transmission electron microscopy has been applied to the quantification of area fractions of calcium-containing cytochemical reaction products in central nervous tissue and the retina of fish. The method of electron spectroscopic imaging using electrons with an energy loss of 250 eV produces images with a very high, structure-sensitive contrast. This is a suitable imaging condition for the reliable detection of reaction products and structural details in unstained ultrathin sections. The images were recorded with a sensitive TV camera and evaluated with the integrated digital image-analysis system of the Zeiss CEM 902 energy-filtering electron microscope. An empirical procedure was developed which objectively detects reaction products and calculates characteristic values, taking into account different staining intensities. This new and sensitive method enabled an assessment to be made of the influence of temperature and light adaptation on cytochemically detectable calcium in nervous tissue of fish. Higher amounts of calcium-containing reaction product were detected in synaptic clefts of the optic tectum in warm-adapted fish than in cold adapted fish. In synaptic vesicles of photoreceptor cells in the fish retina, higher amounts of reaction product were found in dark-adapted fish than in light adapted fish. PMID- 1495090 TI - Localization of Ca(2+)-stores and tissue compartments with a Ca(2+)-binding capacity in the organ of Corti of the guinea-pig by electron energy-loss spectroscopy. AB - The addition of 10 mM CaCl2 to glutaraldehyde fixative leads to the formation of small electron-dense deposits in the organ of Corti of the guinea-pig. These precipitates are mainly attached to cell membranes in contact with different extracellular lymphatic fluids. A higher number of precipitates is localized in the acellular parts of tectorial and basilar membrane. Electron energy-loss spectroscopy (EELS) was used to determine the elemental composition of the deposits formed. The spectra showed a prominent signal at the Ca2+ L2,3 ionization edge. Oxygen could also be detected in all the precipitates analysed. EELS analysis of mitochondria of the inner and outer hair cells after conventional fixation (glutaraldehyde followed by post-fixation in OsO4) revealed a small but significant calcium signal. PMID- 1495091 TI - The use of parallel EEL spectral imaging and elemental mapping in the rapid assessment of anti-cancer drug localization. AB - Both electron spectroscopic imaging (ESI) and electron energy-loss spectroscopy (EELS) have great potential for use in several areas of cancer research. In biologically targeted radiotherapy, cytotoxic drug therapy and boron neutron capture therapy the effectiveness of many drugs is often critically dependent upon the intracellular localization of the agent employed. We describe the use of parallel EEL spectral imaging to assess the penetration and location of the iodine-containing drug meta-iodobenzyl guanidine, of potential value in targeted radiotherapy, and for the rapid detection of boron within borate-adsorbed polystyrene beads, of potential value in boron neutron capture therapy. We also describe elemental mapping of boron following low-temperature embedding. These results show how the techniques could be applied to many forms of cancer research by discussing the validity and limitations of the techniques experimentally. We also provide an outline of other areas in this field which could benefit from the future application of ESI and EELS. PMID- 1495092 TI - The electron energy-loss spectroscopic analysis of inhaled smoke particles. AB - This paper details the use of electron spectroscopic imaging in the elemental analysis of smoke particles inhaled by smoke-death victims. The results show that these particles have a varied structure and composition. Because of this, these particles may play a far more significant role in smoke inhalation injuries than has previous been recognized. PMID- 1495093 TI - Zero-loss energy-filtered imaging of frozen-hydrated proteins: model calculations and implications for future developments. AB - Energy-filtered transmission electron microscopes operating in zero-loss mode are used increasingly to study biological material in frozen-hydrated conditions. The contrast enhancement and improved structural resolution obtainable by this method have been studied using Monte-Carlo model calculations for the scattering processes occurring in such samples. Three models representing typical situations have been analysed, each normalized to minimal beam damage. It is shown that for proteins in thin layers of ice an optimal signal-to-noise ratio is achieved in the 80-120-keV electron energy range. For proteins which have to be embedded in thicker ice layers, a considerably higher acceleration voltage is required. In particular, electron energies above 200 keV would be desirable for electron diffraction work on microcrystals. PMID- 1495094 TI - Electron spectroscopic study (ESI, EELS) of Nanoplast-embedded mammalian lung. AB - The potential of Nanoplast melamine resin embedding for the study of mammalian lung parenchyma was examined by means of electron spectroscopic imaging (ESI) and electron energy-loss spectroscopy (EELS). Samples were either fixed with glutaraldehyde-paraformaldehyde or glutaraldehyde-tannic acid, or were directly transferred to the embedding medium without prior fixation. Organic dehydrants, as well as fixatives containing heavy metals and stains, were omitted. A very high level of ultrastructural detail of chromatin, ribosomes, mitochondria and plasma membranes was achieved by ESI from the Nanoplast-embedded samples. The most prominent gain in ultrastructural detail was achieved when moving from an energy loss just below the L2,3 edge of phosphorus at 132 eV to an energy loss just beyond this edge. This reflects the prominent P L2,3 edge observed by EELS of Nanoplast-embedded samples in comparison with conventionally processed samples. Thus, taking into account possible sectioning artefacts, excellent heterochromatin images which rely on the phosphorus distribution can be obtained from Nanoplast-embedded samples by computer-assisted analysis of electron spectroscopic images. In this respect glutaraldehyde-paraformaldehyde fixation is preferable to glutaraldehyde-tannic acid fixation because the presence of silicon, revealed by EELS, in tannic-acid-fixed samples may introduce artefacts in phosphorus distribution images obtained by the three-window method because of the close proximity of the L2,3 edges of silicon and phosphorus. PMID- 1495096 TI - Address of the president. PMID- 1495095 TI - Laser applications in the lower genital tract. PMID- 1495097 TI - Medical ethics and medical technology. PMID- 1495098 TI - Retinoids and cancer therapy. PMID- 1495099 TI - "High-priority" trials: where are they now? PMID- 1495100 TI - Speed kills--but what about radar guns? PMID- 1495101 TI - Cancer incidence among Danish Thorotrast-exposed patients. AB - BACKGROUND: Studies of groups of patients given injections of the alpha-emitting x-ray contrast medium Thorotrast may provide information on human alpha-ray carcinogenesis. PURPOSE: We re-established a formerly identified cohort of neurological patients receiving injections of Thorotrast for cerebral arteriography and assessed their incidence of cancer. METHODS: Using the national population register, the Danish Cancer Registry, and other registers, we determined the incidence of cancer among Thorotrast-injected patients. Incidence ratios were standardized to the general population and computed for different cancer sites. RESULTS: The cumulative risk for cancer at all sites (excluding brain tumors where the standardized incidence ratio [SIR] was 28) reached 86% 50 years after Thorotrast injection. SIR was greatly elevated at all sites except the brain and CNS (3.3, 95% confidence interval = 3.0-3.7), mainly because of liver cancers (SIR = 126) as well as leukemia (SIR = 10) for which a relationship was found between the time since injection and the estimated dose (but not the age at injection). Other sites with significantly increased risks of cancer included the gallbladder and extrahepatic bile ducts (SIR = 14), peritoneum (SIR = 8.6), sites of multiple myeloma (SIR = 4.6), metastatic sites (SIR = 12), and unspecified sites (SIR = 11). Cancers of the lung and breast also occurred in significant excess, but no relationship between SIR and volume of injected Thorotrast or time since injection was observed. Cancer risk was increased at most other sites, although this increase was not statistically significant. CONCLUSION: Alpha radiation may account for the increased risk of tumors of the liver, gallbladder, and peritoneum as well as leukemia and multiple myeloma, whereas confounding factors most probably contribute to the increased risks at other sites. PMID- 1495102 TI - Quetelet's index and risk of colon cancer in college alumni. AB - BACKGROUND: While previous studies suggest that overweight, middle-aged men may face increased risk of colon cancer, it is unclear whether their weights as young adults influence this risk. It is also unknown whether their level of physical activity affects their risk of developing colon cancer. PURPOSE: To determine the relationship between being overweight in middle-age or young adulthood and colon cancer risk, we prospectively studied alumni of Harvard University. We also investigated whether being overweight influences risk differently for men with different levels of physical activity. METHODS: In 1962 or 1966 (1962/1966), alumni completed questionnaires on weight, height, other sociodemographic characteristics, and medical history. We obtained information on weight and height at college entry from university archives. Alumni (n = 17,595) were followed from 1962/1966 to 1988 for colon cancer occurrence, ascertained from follow-up questionnaires in 1977 and 1988 and death certificates. RESULTS: Between 1962/1966 and 1988, 302 cases of colon cancer were diagnosed. Colon cancer risk increased with higher levels of Quetelet's index (weight [kg]/height [m]2) in 1962/1966. Relative risk per unit increase, adjusted for age, physical activity, and parental history of cancer, was 1.08 (95% confidence interval [CI], 1.04-1.13). Quetelet's index at college entry did not predict risk as well (adjusted relative risk per unit increase, 1.05; 95% CI, 1.00-1.10). The heaviest fifth of alumni during both college time and in 1962/1966 had almost two and one half times the risk of the lightest fifth of alumni (adjusted relative risk, 2.40; 95% CI, 1.40-4.13). When alumni were classified according to activity level in 1962/1966, higher levels of Quetelet's index were significantly associated with colon cancer risk only among those who were less active. CONCLUSIONS: Overweight during middle-age or young adulthood is associated with higher colon cancer risk; in overweight, physically active men, however, the risk of colon cancer may not be increased. PMID- 1495103 TI - Dose-dependent pharmacokinetics of all-trans-retinoic acid. AB - BACKGROUND: Orally administered all-trans-retinoic acid (all-trans-RA) can induce remission in a high proportion of patients with acute promyelocytic leukemia. PURPOSE: To further define the drug's pharmacokinetics, a study of intravenous all-trans-RA was performed in rhesus monkeys. METHODS: A total of nine monkeys received intravenous bolus injections of all-trans-RA. Three different doses (20, 50, and 100 mg/m2) were each tested in three monkeys. Blood samples for determination of all-trans-RA concentration were obtained prior to drug administration and at 5, 10, 15, 30, 45, 60, 75, 90, 120, 150, 180, 240, 360, and 480 minutes after drug administration. RESULTS: Plasma disappearance of all-trans RA was characterized by three distinct phases: a brief, initial exponential decline, followed by a relative plateau in the disappearance curve (the duration of which was dose dependent), and finally a terminal exponential decay. This profile is consistent with a capacity-limited (saturable) elimination process. The first-order (terminal) half-life for all-trans-RA averaged 19 minutes, and the mean clearances were 77, 52, and 59 mL/min for the 20-, 50-, and 100-mg/m2 dose groups, respectively. The mean +/- SD Michaelis constant (Km) for the capacity-limited process was 3.2 +/- 1.9 microM. CONCLUSIONS: Peak plasma concentrations following oral administration of 45 mg/m2 all-trans-RA in humans approach the Km for the capacity-limited process; thus, the dose-dependent pharmacokinetics of all-trans-RA described here may occur within the clinically used dosage range. PMID- 1495104 TI - Association between brain tumors and menopausal status. AB - BACKGROUND: Several lines of evidence have implicated female hormones in the etiology of human brain tumors, meningiomas in particular. PURPOSE: To investigate the relationship between brain tumor development and the hormonal changes manifested during pregnancy and menopause, we analyzed data from female participants in a population-based case-control study of adult brain tumors. This study was conducted in 1987-1988 in the Rhein-Neckar-Odenwald area of the Federal Republic of Germany. METHODS: The study population consisted of 127 women with meningiomas, gliomas, and acoustic neuromas (case patients) and 233 control women who were selected from the general population and frequency-matched by age to the case patients. Information on parity, menopausal status, and previous gynecologic surgeries was obtained through a standardized questionnaire. Case patients and control subjects were compared with the use of the unconditional maximum likelihood estimation of the parameters in a logistic regression model. RESULTS: Our results were not statistically significant; nevertheless, they revealed some interesting trends. No association was found between parity and the development of any of the three histological subtypes of brain tumor (relative risk [RR] = 1.31; 95% confidence interval [CI] = 0.51-2.07). Menopausal women had a greatly reduced risk of developing meningiomas (RR = 0.58; 95% CI = 0.18-1.90), and this effect was most pronounced when menopause had been surgically induced by bilateral oophorectomy (RR = 0.12; 95% CI = 0.01-1.30). Menopausal women had a greater risk of developing gliomas or acoustic neuromas (RR = 1.77; 95% CI = 0.67 4.68), except when menopause was surgically induced, in which case the risk was reduced (RR = 0.33; 95% CI = 0.04-3.09). Oophorectomy after menopause did not appear to influence risk. CONCLUSIONS: Since the onset of menopause is accompanied by cessation of estrogen production, our results support the notion that female hormones play a role in the development of brain tumors. PMID- 1495105 TI - Growth control of human colon cancer cells by vitamin D and calcium in vitro. PMID- 1495106 TI - Body dimension differences in men with or without prostate cancer. PMID- 1495107 TI - Choices. PMID- 1495108 TI - Stat bite. PMID- 1495109 TI - Re: "Author of Canadian breast cancer study retracts warnings". PMID- 1495110 TI - Managed health care: a critical analysis. PMID- 1495111 TI - Risk factors for coronary heart disease in a black population. AB - A matched case control study using population-based controls was done over a 2 year period in an urban, public hospital setting. The object of the study was to determine if the established risk factors for coronary heart disease- hypertension, diabetes mellitus, hypercholesterolemia, cigarette smoking, low socioeconomic status (as reflected by occupational class and educational level), marital status, and obesity were associated with coronary heart disease in a black population. The established risk factors were found to be significant in this patient population, as was obesity. Being divorced or separated was a risk factor for women but not for men. PMID- 1495112 TI - Ethnic differences in patient requests for pregnancy testing. AB - This study identifies a black-white difference in pregnancy test requests and in factors predicting such requests among 324 women tested at an academic family practice in 1986. Data were obtained from encounter sheets filled out by clinicians at the time tests were ordered. Analysis of variance revealed that blacks requested fewer pregnancy tests than whites, and that this finding remained significant (P less than .01) after controlling for the effects of gestational status and other clinical and sociodemographic factors. Blacks were less likely to be married or possess health insurance, but more likely to have been pregnant before. Logistic regressions indicated that factors predicting test requests differed by ethnicity, with symptoms and age predicting test requests among whites, and pregnancy the only significant predictor among blacks. Explanations consistent with these findings include possible ethnic differences in reactions to symptoms and economic factors. Further refinement of these hypotheses and consideration of other alternatives will advance understanding of ethnicity as a factor in test-requesting behavior, and enable clinicians to communicate with and care for black women more effectively. PMID- 1495113 TI - Adolescent drug and alcohol usage: a comparison of urban and suburban pediatric practices. AB - Few pediatric practice-based drug and alcohol surveys have been conducted with adolescent patients. This study reports on similarities and differences in adolescent drug and alcohol use between urban (95% black) pediatric practices and a suburban (89% white) pediatric practice. While there were greater similarities between patient substance use and reported problems than differences, a number of significant differences emerged. White suburban youth were heavier users of tobacco products, alcohol, and inhalants, and experienced more difficulties with blackouts, family conflict, school absence, suicidal ideation, and loss of peer relationships. Other racial/ethnic and practice site differences are discussed. This study highlights characteristics of youth drug abuse in the private pediatric practice setting and implications for the pediatrician in caring for adolescents. PMID- 1495114 TI - Environmental health concerns of the Persian Gulf War. AB - Environmental health concerns in the Persian Gulf are peculiar to the geography of the region. Prevention of heat and solar injury deserves primary consideration, but cold injury also may occur in the desert. Immunizations are recommended against a number of diseases, while malarial chemoprophylaxis is necessary in Iraq and Kuwait. In addition to malaria, other parasitic diseases deserve consideration. Diarrheal diseases, diseases from the desert dust, and products of infected desert animals are of concern. Additional natural hazards are venomous bites from scorpions and desert snakes. Finally, threats of enemy action necessitated protection from nuclear biological and chemical weapons and LASER eye/skin injury. Unexploded ordinance will constitute a continuing hazard into the future. PMID- 1495115 TI - Light hazards in the operating room. AB - The use of high-intensity illumination devices is routine for many ophthalmic diagnostic and therapeutic procedures. However, the exposure of patients to high level photic energy may be damaging even in the absence of visible abnormalities. Devices such as the operating microscope, indirect ophthalmoscope, and endoilluminator are capable of irradiances sufficient to cause retinal damage and should be used with a degree of restraint that reflects a recognition of their potential for phototoxicity. PMID- 1495116 TI - Recurrent intentional injury. AB - Recurrent intentional injury (RII) is a phenomenon that is often noted by those who treat the injured. The authors have observed two groups of assault-related injured patients at the District of Columbia General Hospital Level I urban trauma center to determine the magnitude of this phenomenon in the patient population, to examine the characteristics of such a group of patients, and to identify the risk factors that predispose to repeated assault-related injuries. In a retrospective group of 232 patients admitted over a 4-year period who had sustained penetrating abdominal trauma there were 76 (33%) patients who had been previously treated at our center for assault-related injury. A prospective study of 78 consecutive assault-related injured patients admitted during a 4-month period revealed that 35 patients (45%) had a history of previous hospitalization for injuries as a result of assault. Within the male group (72 patients) 49% exhibited RII. When comparing this group of patients with those patients who had no previous injuries secondary to assault, there was a significantly higher rate of unemployment for the RII group and no difference in educational level. Also, the RII group incurred significantly higher hospital charges when compared to the group of patients who had their first of such injuries ($9673 versus $6973). Efforts to reduce unemployment should be included in preventive strategies if the high incidence of assault-related injury is to be decreased. PMID- 1495117 TI - Driving 'Miss Clarabelle': to a medical education and beyond. The Eighth Annual Ernest Y. Williams, MD, Clinical Scholars of Distinction Awards. PMID- 1495118 TI - Localized pulmonary disease due to Trichosporon beigelii. AB - A case of pulmonary infection caused by Trichosporon beigelii is reported. The infection occurred in a neutropenic patient with acute lymphoblastic leukemia. His chest radiograph showed a 6-cm pulmonary infiltrate in the right midzone and an apical infiltrate on the left. Repeated cultures of bronchoalveolar lavage grew budding yeast that was identified as T beigelii on the basis of morphological, cultural, and biochemical characteristics. He responded to amphotericin-B therapy. Systemic infections caused by this yeast are rare and its causal relationship in localized lung disease has been reported only seven times previously. PMID- 1495119 TI - Antigens involved in the human antibody response to natural infections with Leptospira interrogans serovar copenhageni. AB - Serum samples from patients with leptospirosis were screened by the microscopic agglutination test (MAT), ELISA and by immunoblotting. The latter two tests were performed with L. interrogans serovar copenhageni isolated from human blood culture. Immunoblotting with patients' sera revealed antibodies recognizing several leptospiral components in the molecular weight range 14.5-105 kDa of both IgM and IgG response. All patients' serum samples presented IgM antibodies reacting with a diffuse band of mol. wt of 14.8-22 kDa proteinase-K resistant and most reacted with bands of 26.5-28.7, 38-39 and 43-43.5 kDa. The IgG response appeared to be at variance. Examination of sequential serum samples obtained over a 4-8-month period revealed little change in the profile of antigen recognized after the 40th day of infection. Sera from healthy individuals presented IgM antibodies reacting with several leptospiral antigens, but lacked response against those of diffuse band of 14.8-22 kDa. PMID- 1495120 TI - Study of evoked potentials in human African trypanosomiasis. AB - Human African trypanosomiasis or sleeping sickness has a stage of neurological involvement characterized by the onset of diffuse meningoencephalitis with sleep disturbances and decreased wakefulness. The pathogenesis of this disease is not well understood. We studied auditory, visual, sensory, and motor evoked potentials in 16 patients with trypanosomiasis in the early stage of meningoencephalitis. In all patients, the brain-stem auditory evoked response (BAER) and the pattern-reversal visual evoked response (PVER) were normal. On the other hand, abnormalities of the somatosensory evoked response (SSER) or the motor evoked response (MER) were found in only five cases; however, their relationship to the illness could not be definitely confirmed. The study results indicate that the evaluated pathways were essentially intact, in particular at the level of the brain-stem in the early stage of the disease. Sleep disturbances and decreased wakefulness noted at this stage were thus linked more closely to functional involvement at the level of the sleep centres than to any detectable specific anatomic lesion. PMID- 1495122 TI - Critical analysis of an epidemetrons model for the assessment of bancroftian filariasis endemicity in some areas in Egypt. AB - This study attempted a trial fit of observed epidemiological data in Egypt using the Sasa-WHO-Southgate epidemetrons model to quantify the endemicity and risk of transmission of filariasis. The geometric and arithmetic means (GM, AM) were tried in addition to the recommended four epidemetrons of the model, prevalence rate (PR); median microfilaria density (MfD50); and linear regression coefficients (a and b). Data were based on microfilaria counts in 20 mm3 finger prick night blood samples from all individuals 6 years of age and older of both sexes in a cluster of eight filaria-endemic villages. The study results showed that the model fits satisfactorily in each individual village but major discrepancies occurred when comparisons were made between the villages. PR was closely but by no means perfectly correlated with MfD50, was more closely correlated with GM but less with AM, and showed a rather weak negative correlation with each of a and b by linear regression and by rank order. A possible explanation for these discrepancies is that in areas of recent importation or increase of transmission of filariasis and in areas of great population mobility, observed microfilaria prevalences and microfilaria intensities will not conform to the PR, MfD50, a and b epidemetrons recommended by Sasa (1967), WHO (1967) and Southgate (1974) as descriptive epidemetrons of microfilaraemia. Further studies are warranted. PMID- 1495121 TI - Efficacies of chloroquine, pyrimethamine/sulphadoxine and pyrimethamine/sulphalene against P. falciparum in northeastern Nigeria. AB - The clinical and parasitologic efficacies of oral chloroquine phosphate, pyrimethamine/sulphadoxine and pyrimethamine/sulphalene in treating Plasmodium falciparum malaria were assessed in selected sites of northeastern Nigeria (Zone D of the Primary Health Care (PHC) Programme) using a 14-day standard in-vivo protocol during 1988-1990. Of a total of 2056 children under 5 years screened for infection, for chloroquine trials, 1189 (57.8%) were positive for Plasmodium infection. One hundred and seventy (14.3%) of these positive children were enrolled into the study. Clinically, the drug demonstrated high performance in clearing symptoms of infection. However, varying degrees of parasitologic failure, ranging from delayed clearance through recrudescence to asymptomatic Type-II resistance, were encountered. For tests with pyrimethamine/sulphadoxine and pyrimethamine/sulphalene, 517 and 253 children, respectively, were screened. The corresponding infection rates were 71.6% (370 children) and 71.5% (181 children), with 59 and 34 enrollments. Both drugs were highly effective, clinically and parasitologically. These findings and their implications for the success of the PHC programme for malaria control are discussed. PMID- 1495123 TI - Detection of Brucella melitensis and Brucella abortus by DNA amplification. AB - Suitable reaction conditions and oligonucleotide primers were sought for the detection of Brucella melitensis and Brucella abortus by the polymerase chain reaction. Primers were chosen from within the coding sequence of a gene encoding a 31 kDa B. abortus antigen. The test was shown to be sensitive, and specificity was demonstrated using DNA derived from a panel of Gram-negative pathogens. There was no detectable difference between B. melitensis and B. abortus in the sensitivity of the reaction or in the size of the amplification product. The technique should be applicable in the diagnosis of brucellosis. PMID- 1495124 TI - Disseminated histoplasmosis presenting with ileal perforation in a renal transplant recipient. AB - A renal transplant patient presented with ileal perforation due to histoplasmosis 3 years after transplantation. Mesenteric lymph nodes and lungs were also affected by the disease. She was successfully treated with amphotericin B followed by ketoconazole. PMID- 1495125 TI - Rhinosporidiosis in Pondicherry. AB - One hundred and thirty-nine cases of rhinosporidiosis diagnosed histopathologically over a period of 4 years were analysed. Nasal rhinosporidiosis is common among males who bathe in stagnant ponds while ocular rhinosporidiosis is common among urban females. There is a seasonal variation in the incidence of nasal and ocular rhinosporidiosis. PMID- 1495126 TI - Multidrug resistant enteric fever. AB - Multidrug resistant typhoid fever (MDRT) is becoming an alarming public health problem in and around Pondicherry, South India. A retrospective review of the multidrug resistant typhoid fever cases admitted to the paediatrics ward of JIPMER Hospital, Pondicherry (India) during 1990 is presented. Prolonged pyrexia, chills and rigors, toxaemia, and tender hepatomegaly often more than 3 cm below the costal margin (often without splenomegaly) were striking features of MDRT cases. The incidence of complications was also greater. Positive blood cultures were observed even after weeks of antibiotic therapy, indicating persistent bacteraemia; resistance was almost always observed for multiple drugs (two or more). The fluoroquinolone group of drugs such as ciprofloxacin have been found to be the best for MDRT in terms of rapid response and cost effectiveness. Cefotaxime has moderate efficacy. PMID- 1495127 TI - Diagnostic value of the Widal test for typhoid fever in Singapore. AB - A study was conducted to assess the diagnostic value of the Widal test in patients with bacteraemic typhoid fever. The Widal test was carried out on 25 bacteriologically proven cases of typhoid fever and 50 patients with non-typhoid fever. All the patients with non-typhoid fever had an O agglutinin titre of less than 1:40, while 82% had an H agglutinin titre of less than 1:40. In the patients with typhoid fever, 56% had an O agglutinin titre of greater than or equal to 1:40 and 72% had an H agglutinin titre of greater than or equal to 1:40. Typhoid patients with titres greater than or equal to 1:40 for O and H antigens of Salmonella typhi were significantly different (P less than 0.01) from those with non-typhoid fever. The O agglutinin was highly specific (100%) in the diagnosis of the disease. The study shows that a single Widal test is useful in the diagnosis of typhoid fever in Singapore. PMID- 1495128 TI - An outbreak of salmonellosis following consumption of monkey meat. AB - An outbreak of salmonellosis due to consumption of monkey meat is reported among nine patients of whom one died. S. enteritidis phage type 8 was cultured from the stools of four patients. The spread of salmonellosis due to the consumption of monkey meat has not been reported before. PMID- 1495129 TI - Hospital admissions due to adverse reactions to Chinese herbal medicines. AB - Chinese herbal medicines (CHM) are commonly used in Hong Kong. To determine the importance of adverse reactions to CHM as a cause of medical admissions in Hong Kong, all 1701 patients admitted to two general medical wards at the Prince of Wales Hospital over an eight-month period were prospectively studied. In only three patients (0.2%) was the admission attributed to the adverse effects of CHM. These were life-threatening in two cases ('dazao'-induced angio-neurotic oedema and liquorice-induced hypokalaemic periodic paralysis). Despite this low incidence of adverse reactions, in communities where CHM are commonly used, it is important that there is a continuing effort to collect new information on the safety of these compounds. PMID- 1495130 TI - Sonoelasticity of organs: shear waves ring a bell. AB - Sonoelasticity is the use of ultrasonography to visualize, in real time, the hardness of stiffness of tissues and organs by depicting the tissue's motion in response to an applied vibration source. The applied vibration source is usually of low amplitude and low frequency (less than 0.1 mm displacement and less than 2000 Hz). Under these conditions, the natural vibration response of tissues and whole organs is revealed as a standing wave pattern determined by the low frequency elastic constants of the tissues and their boundary conditions, factors that are not related to the ultrasonic echogenicity. As a result, hard or dense isoechoic tumors that are undetectable by conventional ultrasonography often can be visualized in sonoelasticity imaging by virtue of their altered vibration response. In this report, we demonstrate the appearance of organs such as the breast, liver, and kidney during real-time, in vivo sonoelasticity imaging. The results show that the shape and location of vibration patterns are dependent on the tissues and vibration frequencies; thus, information about the basic elastic properties of tissues should be obtainable. PMID- 1495131 TI - Effect of mode conversion on ultrasonic heating at tissue interfaces. AB - A number of investigators have observed localized heating by ultrasound beams near impedance discontinuities within tissues. It has been suggested that mode conversion to shear waves at impedance discontinuities and subsequent absorption of these waves in a very small distance was the explanation for this heating. A mathematical model for mode conversion at a plane interface between two viscoelastic media is presented. Longitudinal and shear properties are used to calculate the amount of mode conversion that occurs at muscle-air and muscle-bone interfaces. Shear waves in bone are found to be an important source of heating, but shear waves in the muscle provide a negligible effect on heating at the interface. PMID- 1495132 TI - Nucleation and evolution of ultrasonic cavitation in a rotating exposure chamber. AB - The nucleation and progression of ultrasonic cavitation in a rotating exposure chamber were investigated by observing hemolysis of a 0.5% suspension of erythrocytes. Bursts of 1.6 MHz ultrasound beams of 11 W/cm2 spatial peak intensity were synchronized with the rotation to aim the bursts down the axis of a cylindrical chamber. Cavitational hemolysis always occurred in fresh phosphate buffered saline (PBS) solution, but cavitation incidence declined to 38% in 4 day old PBS. The amount of hemolysis for 11 ms or 44 ms bursts with 60 rpm rotation increased in proportion to the number of bursts. Hemolysis was found above a minimum burst duration of 5.5 to 8.3 ms in the normal 2 cm chamber. This did not appear to change for 1 cm or 4 cm chamber lengths, but it did change to about 2.2 ms and about 44 ms for over- and undersaturated gas conditions, respectively. Off times associated with rotation speeds of 15 to 30 rpm reduced the effectiveness of the cavitation, and addition of fixed cells at only 0.01% to 0.02% greatly reduced the hemolysis. For this ultrasonic exposure system, several thousand bubbles, possibly generated from as few as one cavitation nucleus, move across the chamber at up to 10 m/s, each lysing a few hundred cells, and then are cycled back to the front of the chamber by the rotation to reinitiate the cavitation on the next burst. PMID- 1495133 TI - Ultrasonically induced in vitro cell lysis: node-antinode interactions. AB - An attempt was made to discriminate between two hypotheses (standing wave, bubble recycling) of the mechanism of ultrasonically induced cell lysis in a rotating tube. A tube containing an aqueous suspension of P-388 cells was moved back and forth (+/- 3 or +/- 7 mm) during insonation (1 MHz, 5 W/cm2, continuous wave, 5 min). Cell lysis (approximately 20%) occurred. As a positive control, some tubes were also partially or completely rotated during insonation; considerable cell lysis (approximately 60%) occurred. The results are interpreted to suggest that both hypotheses are simultaneously useful in explaining the observed effect of cell lysis in a rotating tube. PMID- 1495134 TI - Gallstone movement during lithotripsy: mechanisms and effects on fragmentation. AB - We sought to examine the mechanisms of gallstone movement and its effect on gallstone fragmentation in vitro. Two experiments were performed in four specially constructed phantoms that allowed decreasing degrees of movement during the application of shock waves. Shock waves caused displacement of the stone from the focus, but the stone and its fragments were returned to the focus by streaming movements in the coupling liquid when the volume of surrounding fluid was small. Streaming movements were ineffective in large volumes. Restraining movements of the gallstone did not improve the results of fragmentation. We conclude that radiation force and the streaming motion of the surrounding liquid account for movements of the stone and fragments during lithotripsy. Lithotripsy is more effective when smaller volumes are used because streaming brings fragments back to the focus of the lithotripter. Total immobilization of the stone in the focus of the lithotripter, however, offers no benefit, probably because it inhibits rotational movement of the stone. PMID- 1495135 TI - Scientifically based safety criteria for ultrasonography. AB - One of the major contributions of E. L. Carstensen to medical ultrasonography lies in the research studies by him and his colleagues on biophysical mechanisms for biological effects. These studies have done much to provide a basis for predicting conditions under which ultrasound will affect living systems. The scientific information that now exists makes possible an improved approach to decisions on safety for diagnostic ultrasonography. In particular, estimates of the maximum temperature produced in a sonographic examination provide an index that can be used to ensure safety from thermal hazards. PMID- 1495136 TI - The envelope that tissue imposes on achievable ultrasonic imaging. AB - Ultrasonic images are imperfect because practical imaging systems have limited spatial, contrast, and temporal resolutions. The envelope within which an ultrasonic imaging system operates is imposed by the physical and biological properties of the imaged tissue. The relevant properties are speed, attenuation, inhomogeneity, nonlinearity, scattering, motion, and the induction of biological damage. The system designer begins by choosing the overall dimensions of the tissue structures to be imaged and the imaging rate. Then, optimization of system design allows the imaging performance to coincide with the envelope imposed by the characteristics of the tissue. PMID- 1495137 TI - Thermodynamic method of B/A analysis of liposome suspensions: prediction via single relaxation theory. AB - The enhanced ultrasonic nonlinear B/A measurements (via thermodynamic method) from liposome systems first reported by Zhang and coworkers are analyzed through relaxation theory. The enhanced ultrasonic absorption and sound velocity dispersion due to lipid structural relaxation are theoretically shown to accurately predict the enhanced B/A findings reported by Zhang and coworkers. PMID- 1495138 TI - The effect of body heating and cooling on the ankle and toe systolic pressures in arterial disease. AB - Although changes in body temperature alter limb blood flow, little information exists on the effect of body heating and cooling on systolic pressures in limbs with arterial disease. Ten patients with stable claudication were studied. Mean ankle systolic pressure index during body cooling (0.79 +/- 0.04) exceeded (p less than 0.01) both the value during routine test (0.69 +/- 0.03) and during heating (0.65 +/- 0.04). The individual, paired difference in ankle systolic pressure index between cooling and heating exceeded 0.15 in seven limbs and between cooling and routine test in five. Mean toe systolic pressure index during heating, but not during cooling, was lower than during routine test (p less than 0.01). There was no significant difference in the mean toe systolic pressure index between heating and cooling. However, compared with heating, toe systolic pressure index increased with cooling in 12 limbs and decreased in eight, including three with loss of measurable pressure. The paired difference in toe systolic pressure index between cooling and heating exceeded 0.15 in 10 limbs and between cooling and routine test in eight; whereas between heating and routine test the paired difference was within 0.15 in all but three limbs. The results indicate that changes in body temperature have significant effects on distal pressures in arterial disease. Preliminary warming in routine tests should improve reproducibility. PMID- 1495139 TI - Photoplethysmography: a valuable noninvasive tool in the assessment of venous dysfunction? AB - We have investigated the photoplethysmography findings in 152 patients admitted to the Middlesex Hospital Vascular Laboratory with suspected lower limb venous disease, and we compared the results obtained with patient grouping using clinical criteria and the presence of reflux on color duplex scanning. All photoplethysmography traces were normalized with use of computer software to enable direct comparison between the traces. The parameters investigated were the 95% and 50% refilling times and the initial gradient of the refilling curve. Receiver operating characteristic curves were constructed to determine which parameter was the most useful predictor of disease and to identify which value within each observation gave the greatest sensitivity and specificity. We found a large overlap between interquartile values for all three parameters, with limbs grouped both clinically and by duplex scanning, making differentiation between normal and abnormal limbs difficult on the basis of photoplethysmography traces alone. We found that a 95% refilling time of less than 15 seconds indicated venous dysfunction with the greatest sensitivity and specificity and suggest that this value is most useful. Photoplethysmography readings are reproducible, noninvasive, and correlate well with the presence of clinical disease, and photoplethysmography remains useful in the assessment of venous dysfunction. PMID- 1495140 TI - Vascular laboratory utilization and payment: report of the Ad Hoc Committee of the Western Vascular Society. PMID- 1495141 TI - Silent myocardial ischemia monitoring predicts late as well as perioperative cardiac events in patients undergoing vascular surgery. AB - In a previous study we have shown that perioperative monitoring for silent myocardial ischemia can noninvasively identify those patients undergoing peripheral vascular surgery who are at significantly increased risk for perioperative myocardial infarction. In the present study a group of 385 patients undergoing peripheral vascular surgery was studied long-term as well as short term to determine whether perioperative monitoring for silent ischemia can identify those patients who are at significantly increased risk of late cardiac death or late cardiac complications as well as those patients at increased risk of perioperative myocardial infarction. All patients were monitored before, during, and after operation and were divided into two groups on the basis of results of monitoring: patients whose total duration of silent ischemia as a percentage of the total duration of perioperative monitoring was 1% or greater (group I, n = 120) and those for whom this value was less than 1% (group II, n = 265). Among patients in group I 13.3% (16 of 120) suffered a perioperative myocardial infarction in contrast to only 1.1% (3 of 265) patients in group II (p less than 0.001). Multivariate logistic regression analysis of preoperative and perioperative characteristics showed that the presence of a total perioperative percent time ischemic 1% or greater and age were the only significant predictors of perioperative myocardial infarction.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1495143 TI - Epidemiology of carotid endarterectomies among Medicare beneficiaries. AB - Extensive debates exist in the literature on the indications, effectiveness, and risks of carotid endarterectomy. However, no investigations analyze the procedure's epidemiology. Medicare paid for essentially all carotid endarterectomies on patients over 65 years old, more than two thirds of all such surgery. Accordingly, we identified all 1985 to 1989 Medicare bills for ICD-9-CM code 38.12. This report found an average annual decrease of 6.4% in the frequency of carotid endarterectomies. Higher proportions and incidence rates occurred among 65- to 79-year-old people, men, and whites. Larger, urban, and nonprofit hospitals performed the procedure more often. The number of hospitals performing this procedure has increased over time. Mortality rates within 30 days decreased from 3.0% of procedures in 1985 to 2.5% in 1989. Higher than average death rates occurred among older, male, and black patients, and in low volume hospitals. Clinical trials undertaken in large, urban, teaching, high-volume institutions reported only 1% deaths. The institutions actually performing carotid endarterectomies differ from the clinical trials in their demography and perioperative mortality rates. This difference in community practice may limit the applicability of the clinical trials. PMID- 1495142 TI - Elastin content, cross-links, and mRNA in normal and aneurysmal human aorta. AB - Although elastin depletion is thought to be an etiologic factor in abdominal aortic aneurysm, little is known about its transcription and posttranslational modification in normal and diseased human aorta. Our objectives were to quantify total elastin and elastin cross-links (desmosine/isodesmosine [DID]) and to determine if elastin mRNA was detectable in the disease-prone infrarenal aorta from patients with abdominal aortic aneurysm and a comparative group with no aneurysmal diseases. After preliminary extraction and thermolysin digestion, content of DID and the elastin tetrapeptide, valine-alanine-proline-glycine (VAPG), were determined by high-performance liquid chromatography. Tissue mRNA was studied by Northern blot analysis. Mean values (+/- SE) were compared by Student's t test. The proportion of insoluble elastin was markedly decreased in abdominal aortic aneurysm tissue (1.3% +/- 0.04% vs 12% +/- -2.8%; p less than 0.001). There was no difference in the small percentage of elastin solubilized during extraction in abdominal aortic aneurysm (5.3% +/- 1%) and no aneurysmal disease (6.0% +/- 1.2%; p = 0.71) tissues. The DID concentration of insoluble elastin was not different for abdominal aortic aneurysm and no aneurysmal disease tissue (0.18% +/- 0.07 vs 0.18 +/- 0.05 nm DID/nm VAPG; p = 0.97). On the basis of VAPG content, only 26% +/- 4% of the sodium hydroxide insoluble residue from abdominal aortic aneurysm was elastin; the predominate protein(s) was high in polar amino acids. Elastin mRNA was detectable in all tissues.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1495144 TI - Long-term results of infrainguinal revascularization with polytetrafluoroethylene: a ten-year experience. AB - Two hundred fifty-eight patients underwent 322 infrainguinal revascularizations with use of polytetrafluoroethylene (PTFE) between 1978 and 1988. The indication was limb salvage in 190 (59%) reconstructions. Two hundred nineteen (68%) were above-knee, and 75 (23%) were below-knee femoropopliteal bypasses. Twenty-eight (8.6%) were femoral-infrapopliteal bypasses, all done for limb salvage. Follow-up ranged from 24 to 144 months (mean, 66 months). The perioperative mortality rate (1 to 30 days) was 3.4% (9 patients), with no significant difference according to indication (2.9% vs 3.7%). Actuarial primary patency at 8 years for the entire series of femoropopliteal bypasses was 53% (above knee 53%; below knee 39%; p less than 0.05), and improved with additional procedures for a secondary patency of 72%. Femoropopliteal bypasses done for severe claudication had an 8-year actuarial primary patency of 63%, compared with 38% for limb salvage (p less than 0.02). Actuarial limb salvage in the latter group at 8 years was 66%. Femoral infrapopliteal reconstructions with PTFE had a significantly lower primary patency at 3 years (22%, with a 37% limb salvage). Sixty-four percent of the failures for all reconstructions (N = 111) occurred within 12 months, with remarkable stabilization of patency curves beyond that interval. This experience represents the largest reported series of PTFE reconstruction with longest follow up to date and may serve as a basis for comparison of other conduits. These results suggest an important role for PTFE in femoropopliteal revascularization and a limited role of this prosthetic conduit in femoral-infrapopliteal arterial reconstructions. PMID- 1495145 TI - A comparative analysis of transcutaneous oximetry (tcPO2) during oxygen inhalation and leg dependency in severe peripheral arterial occlusive disease. AB - Transcutaneous oximetry (tcPO2) performed during either oxygen inhalation or leg dependency was intra-individually compared in 64 patients suffering from a peripheral arterial occlusive disease, with and without critical limb ischemia. Among the 81 extremities investigated, 29 had a moderate peripheral arterial occlusive disease (6 in stage I, 23 in stage II) and 52 were initially affected by rest pain or ulceration (stage III/IV). Thirty-seven legs out of the latter improved under conservative treatment. In the remaining 15 limbs, vascular surgery or an amputation became necessary. The tcPO2 was measured at the forefoot with the patient in supine and sitting positions while breathing room air and in the supine position while inhaling 100% oxygen. In limbs with a tcPO2 below 15 mm Hg of patients in the supine position breathing room air, leg dependency generally provoked larger tcPO2 increases than oxygen inhalation. This difference between oxygen inhalation while supine and room air breathing leg dependency tcPO2 values exhibited an approximately linear correlation with the resting tcPO2. Responses of tcPO2 to leg dependency and oxygen inhalation seemed to reflect different mechanisms, that is, microvascular flow redistribution and supine perfusion reserve, respectively. The best discrimination of critical limb ischemia was observed for the tcPO2 of patients breathing room air while in the supine position, which was not surpassed by either the oxygen inhalation or the leg dependency test. Satisfactory results were achieved by combining limits for, first, supine (10 mm Hg) and sitting (45 mm Hg) tcPO2, as well as, second, ankle arterial pressure (60 mm Hg) and supine tcPO2 (10 mm Hg). PMID- 1495146 TI - Prevention of smooth muscle cell phenotypic modulation in vein grafts: a histomorphometric study. AB - This is a prospective study of the relationship between graft preparation technique and the subsequent morphologic fate of vein grafts. Paired vein grafts (optimal vs injury prepared) were placed in a canine model and removed over time. Vein grafts intentionally injured by warm saline storage demonstrated endothelial and smooth muscle cell damage. In the acute postimplantation period, platelet adhesion and white cell infiltration of the graft were present. By 7 days, the endothelium had "healed", but the underlying smooth muscle cells had modulated and were of the transitional or synthetic phenotype. This persisted at 30 days, but by 60 days the graft wall had remodeled to a contractile smooth muscle cell phenotype. Changes in the extracellular matrix were greatest at 30 days corresponding to changes in the smooth muscle cell phenotype. None of these injurious responses were noted in optimally prepared, papaverine treated vein grafts. The combined intima and media (lumen to adventitial edge) was measured at baseline and at graft excision with use of digitized graphic techniques. The intimal/medial thickness of injured vein graft walls was always greater than that of pair-matched optimally treated vein grafts (p less than 0.01 analysis of variance). Optimal preparation of vein grafts is effective in minimizing endothelial and smooth muscle cell injury at the time of arterial reconstruction. This preservation of endothelial and smooth muscle cell integrity prevents subsequent morphologic changes associated with the "arterialization response". PMID- 1495147 TI - Effect of prostaglandin I2 analogue TRK-100 on the suppression of intimal fibrous proliferation. AB - This study investigated the effect of prostaglandin I2 analogue (TRK-100) on the healing of arterial anastomoses. The infrarenal abdominal aorta was divided and reanastomosed immediately in rabbits. A control group of rabbits were fed commercial rabbit food (ORC 4); a cholesterol group of rabbits were fed a diet with 1% cholesterol added to ORC 4; and a TRK group of rabbits received the same diet as the cholesterol group, but TRK-100 was given subcutaneously at a dose of 0.3 mg (TRK-I group) or 1.0 mg (TRK-II group) every other day. After 3 months a blood sample was taken for biochemical analysis, and the abdominal aorta was harvested for histologic examination. The serum lipid and thromboxane B2 concentrations and the thromboxane B2/6-keto prostaglandin F1 alpha ratio in the TRK groups were significantly lower than in the cholesterol group. The proliferative connective tissue did not cover the anastomotic suture line in either the control or the TRK groups. However, the suture line was covered completely by connective tissue in the cholesterol group. Intimal thickness in the cholesterol group was greater than in either the control or the TRK-II group (p less than 0.01 and p less than 0.05, respectively). These data suggest that TRK-100 may suppress intimal fibrous proliferation at anastomotic suture lines by a mechanism affecting the thromboxane B2/6-keto prostaglandin F1 alpha ratio. PMID- 1495148 TI - Intraoperative arteriography and carotid surgery. AB - To minimize morbidity in carotid surgery we have adopted the practice of routine operative arteriography. In our total experience of 692 carotid artery reconstructions done since 1979 no arteriography was used for the first 157 procedures. The combined morbidity and mortality rate in this group was 4.5% (4 strokes and 3 deaths as a result of stroke). After 157 carotid operations we used intraoperative arteriography on all cases, and the neurologic morbidity and mortality rate for this part of the series was 1.3% (6 strokes and 1 fatal cerebral hemorrhage). One death was due to myocardial infarction. The difference in ischemic neurologic sequellae between these two groups was statistically significant by chi-square analysis (p less than 0.01). Although the difference in these two cohorts could be related to the "learning curve" effect, it is unlikely that this is the only reason for the difference. Intraoperative arteriography has demonstrated unsuspected stenoses, occlusions, flaps, and kinks. There was also a statistically significant difference (p less than 0.01) in the number of reoperations for recurrent stenosis: 3.8% in the first group and 0.8% in the second group. No complications were thought to be directly associated with the arteriogram. Since the development of better digital imaging systems for the operating suite, this technique is much more easily used than when it was first described. PMID- 1495149 TI - The ischemic window: a method for the objective quantitation of the training effect in exercise therapy for intermittent claudication. AB - Twenty-two patients with intermittent claudication were prospectively enrolled in a 12-week program of supervised, graded treadmill exercise therapy. Severity and distribution of arterial occlusive disease were ascertained by noninvasive determination of segmental lower extremity blood pressures and waveforms. No attempt was made to modify risk factors for atherosclerotic occlusive disease. The exercise-induced reduction of the ankle pressure and its recovery were recorded over time, and the area under this curve, the "ischemic window," represents the severity of the ischemic deficit. Absolute systolic ankle pressure, ankle-brachial index, maximum walking time, claudication pain time, and the ischemic window were measured before and after exercise training in all subjects. Maximum walking time and claudication pain time increased 659% and 846%, respectively, among the 19 patients completing the 12-week program (p = 0.001; p = 0.0002). These patients underwent a mean reduction of 58.7% in the ischemic window after a standardized workload (p less than 0.05), and this correlated with the degree of symptomatic improvement. Absolute ankle pressure and ankle-brachial index were unchanged after exercise training. This study confirms the utility of supervised exercise therapy in the treatment of intermittent claudication. The ischemic window is a useful method for quantifying the ischemic deficit produced by exercise and provides a reproducible means of documenting functional improvement in patients undergoing exercise training. PMID- 1495150 TI - A prospective randomized evaluator-blinded trial of two potential wound healing agents for the treatment of venous stasis ulcers. AB - Chronic wounds such as venous stasis ulcers have become a socioeconomic problem. Even with successful initial management, the recurrence rate approaches 70%. With the advent of new wound healing agents, nonoperative attempts to heal these wounds appear indicated. This study reports a prospective randomized evaluator blinded trial comparing two potential wound healing agents to an inert vehicle placebo. Eighty-six evaluable patients completed the trial. Silver sulfadiazine 1% in a cream proved to statistically reduce the ulcer size compared with a biologically active tripeptide copper complex 0.4% cream formulation or the placebo. There was no difference between the latter two treatments. Silver sulfadiazine has been shown to allow keratinocyte replication and to have antiinflammatory properties. In this trial its antibacterial action was not used since all ulcers had comparable bacterial levels (less than or equal to 10(5)/gm of tissue) before treatment. These results suggest that the silver sulfadiazine cream used in this study may facilitate healing in wounds healing largely by the process of epithelialization. PMID- 1495151 TI - Transjugular intrahepatic portosystemic shunts: preliminary results in 25 patients. AB - A retrospective study of transjugular intrahepatic shunts performed between June 1990 and June 1991 is reported. Twelve patients were actively bleeding at the time of the procedure; 12 other patients had had one to five bleeding episodes within the previous 2 weeks, and one patient had massive ascites from Budd-Chiari syndrome. Most patients had severe liver disease: 21 Child's class C, three Child's class B, and one Child's class A. Transjugular intrahepatic shunting was technically successful in all cases. Portal vein pressures were reduced on average from 36 +/- 7 cm H2O to 22 +/- 6 cm H2O. Variceal bleeding ceased after transjugular intrahepatic shunting in all patients who were actively bleeding. Five patients died (30-day mortality, 20%), and eight patients subsequently underwent elective liver transplantation. The transjugular intrahepatic shunts in the 12 other patients have remained patent an average of 5.5 months. Shunt occlusion occurred in three patients at 21, 24, and 102 days, respectively. All three occlusions were successfully reopened with percutaneous techniques, yielding a primary shunt patency of 88% and secondary shunt patency of 100%. Complications included new onset encephalopathy in one patient, which cleared with medical therapy and transient renal failure in one patient. These preliminary data suggest that transjugular intrahepatic shunting is a safe and effective therapy for the short-term treatment of patients with variceal hemorrhage, particularly in patients with severe liver disease awaiting transplantation. The long-term benefit of transjugular intrahepatic shunting awaits further follow-up. PMID- 1495152 TI - Acute aortic occlusion as a result of extrinsic compression from peritoneal encapsulation. AB - Acute aortic occlusion frequently occurs with catastrophic visceral, spinal, or lower extremity ischemia and is most often caused by embolic or thrombotic events in older individuals with known cardiovascular disorders. This case describes the rapid development of the clinical signs of acute aortic occlusion in a young and completely healthy individual. Aortic occlusion was produced by extrinsic compression of the juxtarenal aorta from a closed-loop small intestinal obstruction contained within a peritoneal encapsulation, an extremely rare intraabdominal developmental anomaly. PMID- 1495153 TI - Perforation of a vein valve leaflet: a mechanism for incomplete valve incision during in situ bypass. AB - The modified Mills retrograde valvulotome has been our preferred instrument for valve incision for in situ saphenous vein bypass. In one case during completion angioscopy the valvulotome was identified to have perforated a posterior valve leaflet and left the leaflet intact. This intact leaflet was identified and incised under direct vision. Valve leaflet perforation by the valvulotome tip is proposed as one possible mechanism for incomplete valve lysis. PMID- 1495154 TI - Septic emboli from a radial artery catheter with local manifestations of subacute bacterial endocarditis. AB - Septic emboli, giving rise to physical signs similar to those of subacute bacterial endocarditis, are extremely rare complications of radial artery catheterization. A case is reported with splinter hemorrhages and Janeway lesions, resulting from an infected radial artery catheter. Five other cases with these signs are collected from among 21 patients with localized septic complications described in the literature. The duration of radial artery catheterization was 4 days or longer in all cases, and Staphylococcus aureus was the offending agent in all. We conclude that arterial lines should be removed as early as possible, and in any case they should be pulled out at the earliest sign of a local complication. In the presence of signs of local infection, antistaphylococcal treatment should be given until results of cultures are available. PMID- 1495155 TI - Distribution of valvular incompetence in patients with venous stasis ulceration. PMID- 1495156 TI - Real-time color duplex scanning after sclerotherapy of the greater saphenous vein. PMID- 1495157 TI - Clinical significance of late potentials in patients after intracardiac operation for congenital heart disease. AB - The aim of this study was to evaluate the late potentials (LPs) in postoperative patients with congenital heart disease (CHD) and to study the association with the clinical characteristics in the postoperative patients with LPs. Signal averaged electrocardiogram (SA-ECG) was recorded in 119 postoperative patients aged 4 to 23 years and compared with those in age matched 49 healthy volunteers with and without right bundle branch block. Based on control data, criterias of LP were defined and altered in the presence of bundle branch block. Abnormal SA ECGs were not detected in the patients with non-cyanotic CHD. However, abnormal and borderline SA-ECGs were recognized in 5 (12%) of 42 patients after intracardiac operation for tetralogy of Fallot and 3 (30%) of 9 patients after Rastelli's operation. The patients with abnormal and borderline SA-ECGs were significantly older at the time of operation, and had more frequent ventricular arrhythmias (7/8: 3/111, p less than 0.01) and depression of the ST-T segment on ECG (7/8: 11/111, p less than 0.01), compared with the normal SA-ECG group. Abnormal SA-ECGs including those of borderline patients were 50% sensitive and 96% specific for documented ventricular arrhythmias. However, there was no association between abnormalities of SA-ECGs and cardiomegaly on chest X-ray or left ventricular ejection fraction on echocardiogram. These results indicate that prolonged exposure to hypoxia may be the main cause of the primary role in the development of LPs. And late surgical intervention may result in histological background for the development of LPs. PMID- 1495158 TI - Sequential appearance of fibronectin, collagen and elastin during fatty streak initiation and maturation in hypercholesterolemic fat-fed rabbits. AB - To elucidate whether tissue fibronectin increases in the early stages of atherogenesis induced by hypercholesterolemia without mechanical trauma, we investigated sequential changes in the distribution of tissue fibronectin during fatty streak initiation and maturation in the aortas of hypercholesterolemic fat fed rabbits. The presence of fibronectin was examined on immunoperoxidase stained tissue specimens with the aid of a microscope-photometric technique. Twenty male albino rabbits were used. Cholesterol supplemented chow (1%) was given for 4 weeks (n = 6), 8 (n = 5) or 14 weeks (n = 5). A membrane-like layer positive for fibronectin was observed along the endothelium in the normal aorta. After 4 weeks of the cholesterol-feeding, fatty streaks were initiated in the intima, where fibronectin was more densely accumulated than the normal intima. After 8 weeks of the cholesterol-feeding, fatty streaks were expanding, associated with the dense staining for fibronectin. After 14 weeks, fibronectin was still concentrated in the endothelial layer and also in the superficial areas of the thickened intima, but decreased in the deep areas of the thickened intima where collagen and elastin appeared as bundles. The photometric data of fibronectin supported these visual observations. Thus, fibronectin appeared early and disappeared later in the intima during the process of fatty streak initiation and maturation. These findings suggest that in hypercholesterolemia without mechanical endothelial injury, fibronectin may play an important role in an early process of atherogenesis. PMID- 1495159 TI - Augmented contractile response to endothelin and blunted endothelium-dependent relaxation in post-ischemic reperfused coronary arteries. AB - To elucidate the pathogenesis of the post-ischemic vascular injury in reperfused coronary arteries, the left anterior descending coronary artery (LAD) was occluded for 30 min or 60 min in 26 dogs. After 120 min of reperfusion, vascular strips were prepared from LAD and the left circumflex coronary artery (LCX) as control, and suspended in organ chambers containing Krebs-Henseleit solution and vascular reactivity was evaluated pharmacologically. In a separate experiment, LCX-strips from 12 dogs were subjected ex vivo to blood cell-free simulated ischemia by the substitution of perfusate to hypoxic, low pH and high K+ for 60 min and the following 60 min of reoxygenation. Vascular responses to various agents were compared prior to and after simulated ischemia. Vascular injury was also investigated histologically with electron microscopy. As the results; significantly blunted endothelium-dependent relaxations to acetylcholine (10(-6) M) and Ca-ionophore (A-23187: 10(-6) M) in LAD-strips compared to LCX were noticed (43.7 +/- 4.8 vs 61.6 +/- 7.3%, 22.7 +/- 5.2 vs 47.9 +/- 8.4% in % relaxation, respectively). Augmented contractile response selective to endothelin was also observed in reperfused vessels (LAD) compared to control vessels (10(-9) M: 105.4 +/- 19.5 vs 42.4 +/- 12.3% of 20 mM-KCl induced contraction, p less than 0.01). Electron microscopy revealed partial detachment and blebbing of endothelial cells in reperfused coronary arteries. Similar changes were also observed in the simulated ischemia and reoxygenation study, but the augmented response to endothelin was seen only when polymorphonuclear leukocytes (PMN) activated with phorbol myristate acetate were added. Our results suggest that endothelial injury does not essentially depend on PMN, but PMN promote augmented response to endothelin. These changes indicate that enhanced spasmogeneity is present in reperfused arteries, which may contribute to post-infarction angina and prolonged myocardial dysfunction after reperfusion. PMID- 1495161 TI - An orange-shaped aortic root aneurysm in aortitis syndrome with severe aortic regurgitation. AB - A 57-year-old man, who had undergone aorto-coronary bypass surgery 4 years before when the shape of the ascending aorta had been normal, had a unique orange-shaped aortic root aneurysm associated with severe aortic regurgitation and congestive heart failure. Replacement of the aneurysm and the aortic valve was successfully carried out, and histopathological examination revealed that the aneurysm was caused by aortitis syndrome. PMID- 1495160 TI - Acute myocardial infarction in a young adult as possible sequela of Kawasaki disease--a case report of successful intracoronary thrombolytic therapy and histological study of an aneurysm. AB - Emergency coronary angiography in a 28-year-old male suffering an acute anteroseptal myocardial infarction revealed complete obstruction of the left anterior descending artery in association with multiple aneurysms of the 3 major coronary arteries. Successful intracoronary thrombolytic treatment with urokinase infusion directly into the infarct-related artery was performed 2 h after the onset. Follow-up left ventriculogram showed preservation of left ventricular wall motion. Fifty days after the infarction, he underwent aorto-coronary bypass surgery. Histological examination of the biopsy specimen obtained from the aneurysm of the distal portion of the right coronary artery revealed that the 3 layer architecture of the arterial wall had been completely lost. The wall was replaced by fibrotic tissue, with slight mononuclear cell infiltration around the small vessels, but no acute inflammatory reaction or atheromatous change was seen. In spite of the presence of the coronary risk factors of hypertension and hyperlipidemia, angiography revealed no evidence of atherosclerosis of systemic arteries. It is suggested that the coronary aneurysms in this case are possible sequelae of Kawasaki disease in childhood. PMID- 1495162 TI - Myocardial energetics and cardiac function of preserved rat heart. AB - We studied mitochondrial function in relation to ATP production and its relationship with myocardial oxygen consumption (VO2) and total mechanical energy using isolated rat hearts after 8, 12, and 24 h of hypothermic preservation. In isovolumic contraction, ventricular contractility and total mechanical energy were respectively assessed by the end-systolic elastance (Ees) and pressure volume area (PVA). Ees significantly decreased after hypothermic ischemia, although the difference was not significant between 8 and 12 h. In contrast, VO2 measured at each left ventricular volume increased after hypothermic ischemia. PVA and VO2 were found to stay in linear correlation after prolonged hypothermic ischemia, although VO2 at null PVA and VO2 to PVA ratios significantly increased after hypothermic ischemia, especially after 12-h ischemia. Mitochondrial oxidative phosphorylation significantly decreased after hypothermic ischemia for longer than 12 h. These results indicate that mitochondrial oxidative phosphorylation was impaired due to long time hypothermic ischemia especially after 12-h ischemia. We conclude that energy uncoupling between VO2 and PVA in hypothermically preserved heart is attributable to disturbed mitochondrial oxidative phosphorylation and that 8 h is a critical point for efficient conversion of energy from VO2 into PVA in rat heart. PMID- 1495163 TI - Left ventricular contractility and energetic cost in disease models--an approach from the pressure-volume diagram. AB - Left ventricular contractility and the energetic cost of contraction were assessed in various disease models in experimental animals utilizing frameworks of Emax (left ventricular contractility index) and pressure-volume area (PVA, a measure of total left ventricular mechanical energy expenditure) derived from the pressure-volume (P-V) diagram. Under various contractile conditions, PVA linearly correlates with myocardial oxygen consumption per beat (VO2) in a load independent manner. The reciprocal of the slope of the linear VO2-PVA relation indicates "contractile efficiency" (the energy transduction efficiency from oxygen to total mechanical energy). It was similar between dog and rabbit hearts (about 40%) and was not significantly affected by enhanced contractility with calcium, epinephrine, or cardiac cooling, or by depressed contractility with propranolol, decreased coronary perfusion pressure, or stunned myocardium. However, in thyrotoxic rabbit hearts contractile efficiency was significantly depressed compared to normal hearts. On the other hand, the VO2 intercept of the VO2-PVA relation (PVA-independent VO2), which reflects VO2 for non-mechanical activities such as excitation-contraction coupling and basal metabolism, positively correlates with Emax. Therefore, the ratio of an increase in PVA independent VO2 to an increase in Emax indicates "oxygen cost of contractility". Oxygen cost of contractility was higher in stunned myocardium than in normal hearts, suggesting that the energy cost of calcium handling is elevated in stunned myocardium. Thus, using the frameworks of Emax and PVA, we can interconnect cardiac mechanics and energetics. Further, using the concepts of contractile efficiency and oxygen cost of contractility, we can approach the pathogenesis of variously altered contractile conditions. PMID- 1495164 TI - A contractility index independent of myocardial length. PMID- 1495165 TI - Ventricular-load optimization in patients with heart failure. AB - The effects of unloading or inotropic agent in 22 patients with dilated cardiomyopathy were assessed in terms of optimal coupling between the ventricle and arterial system. In 13 patients (group A), lower body negative pressure (LBNP) was applied to reduce preload and nitroprusside was used to decrease afterload. In 9 patients (group B), dobutamine was used to enhance inotropic state. In all patients, the direct arterial pressure was simultaneously recorded with left ventricular echocardiogram as the pressure was elevated by phenylephrine. The left ventricular contractile properties were defined by the slope (Ees) of the end-systolic pressure-volume relation. The arterial system properties were expressed by the slope (Ea) of the end-systolic pressure-stroke volume relation. When the Ea/Ees ratio ranged from 0.5 to 1.0, both external work and mechanical efficiency are nearly maximized. In group A, baseline ventricular load coupling was characterized by an increase in the Ea/Ees ratio (1.96 +/- 1.08) where the heart could maximize neither external work nor mechanical efficiency. Ea/Ees significantly fell to 1.45 +/- 0.77 with nitroprusside, while increasing to 2.37 +/- 1.17 during LBNP. In group B, Ea/Ees was decreased from 1.43 +/- to 0.82 +/- 0.47 with dobutamine. It is concluded that reduction in afterload rather than preload, or augmentation of contractility could restore optimal ventricular-load coupling in patients with severe cardiac dysfunction. PMID- 1495166 TI - Assessment of left ventricular function using a conductance catheter in the human heart. AB - To validate the usefulness of the conductance catheter in the clinical setting, we first studied the accuracy of human left ventricular (LV) volume measured by conductance catheter in comparison with LV volume measured by biplane angiography in 19 patients with heart disease. Secondly, we made a comparison of end-systolic pressure volume relation (ESPVR) and preload recruitable stroke work (PRSW) relation in 60 patients with heart disease. Thirdly, we studied the myocardial oxygen consumption (VO2)-pressure volume area (PVA) relation to assess contractile efficiency in 22 patients with heart disease. There was a good correlation between the corrected conductance volume (Vcc) and the angiographic volume (V angio) (Vcc = 0.94 Vangio + 5.4, r = 0.94, P less than 0.001). Two relations, ESPVR and PRSW, were well described by straight lines with high correlation coefficients. However, PRSW was a more linear contractile index than ESPVR. The reciprocal of the slope of the VO2-PVA relation was approximately 40% in the control contractile state. We conclude that the conductance catheter accurately measures LV volumes and facilitates the assessment of ESPVR, PRSW and contractile efficiency in human LV. PMID- 1495167 TI - Ventricular contractility evaluated by mechanical perturbation of the myocardium- experimental and clinical approach adopting small amplitude vibration input. AB - Small amplitude mechanical vibration has been reported to depress the function of the isolated left ventricle in an amplitude dependent manner. We examined, 1) contractility and preload dependency of the magnitude of functional depression (VID) by applying 50 Hz, 2 mm amplitude vibration to the epicardium of the canine left ventricle and 2) whether VID is present in the failing human ventricle. The magnitude of VID was independent of preload in the physiological range of LV volume showing peak LV pressure greater than 75 mmHg, and VID was correlated with Emax at each inotropic state. In the in-situ condition, VID appeared only in the failing condition with a sensitive increase at a mild level of heart failure. In a study during routine cardiac catheterization (n = 27), the presence of VID has been demonstrated in the human ventricle (n = 18). The magnitude of VID was correlated with ejection fraction (EF) as, VID in peak LV pressure (mmHg) = 80.6 110 x EF, r = 0.84, p less than 0.01 in patients with EF less than or equal to 0.7 (n = 14). Therefore, we concluded that VID could be a clinical tool for evaluation of mild heart failure. PMID- 1495168 TI - Contributors of characteristic mitral flow velocity pattern in congestive heart failure--from clinical observations back to experimental validations. AB - Mitral flow velocity pattern in patients with left ventricular (LV) diastolic dysfunction usually includes decreased peak early diastolic filling velocity (E), slowed deceleration of the early diastolic filling wave and increased peak filling velocity at atrial contraction (A). However, the abnormal mitral flow velocity pattern can be normalized in the presence of concomitant congestive heart failure. In such cases E can be equal to or even higher than normal, its deceleration is normal or faster than normal value, and A can be normal or lower than normal value. Clinical observations in patients with severe heart failure showed that the mitral flow velocity pattern changes with vasodilating therapy, reflecting the changes in the left atrial (LA) to LV pressure difference rather than those in the absolute LA pressure or LV pressure alone. This was validated in the canine study in which levels of LV dysfunction were made by the injection of microspheres into the left coronary artery to study the interrelation among the mitral flow velocity pattern and LA and LV pressures. In this experiment, the changes in the mitral flow velocity pattern could not be explained by the changes in LA or LV pressure alone but was better explained by the changes in the LA to LV pressure difference. Not only LA-LV crossover pressure but also LA compliance seem to be important as determinants of LA pressure level in diastole. In addition to LV relaxation rate, incompleteness of relaxation, elastic recoil and LV passive elastic properties, extracardiac constraint is also considered to be an important determinant of the level of the LV diastolic pressure and hence of the mitral flow velocity pattern at least in the presence of congestive heart failure. Thus, mitral flow velocity pattern is determined by the interaction of LA and LV pressures, both of which are affected by chamber properties as well as loading conditions. PMID- 1495169 TI - Dynamic determinants of left ventricular early diastolic filling in old myocardial infarction. AB - The determinants of left ventricular early diastolic filling were assessed in 15 patients with old myocardial infarction. The left atrial pressure (LAP) and left ventricular pressure (LVP) were simultaneously measured by a Millar's multisensor micromanometer with the pusled Doppler mitral inflow velocity at baseline and during angiotensin infusion (20 ng/kg/min). Cardiac output was measured by a thermodilution method. LV peak systolic pressure and end-diastolic pressure were significantly (p less than 0.001) increased during angiotensin infusion from 137 +/- 19 to 170 +/- 21 mmHg and from 13.3 +/- 5.9 to 20.4 +/- 6.2 mmHg, respectively. Cardiac index was significantly decreased during angiotensin infusion. Heart rate, diastolic time, and peak positive dP/dt were unchanged. Although the LA-LV peak pressure gradient[(LAP-LVP) max] was unchanged (from 2.8 +/- 1.0 to 3.0 +/- 1.4 mmHg), the pressure gradient interval (the interval between the first and second points of transmitral pressure crossover) was significantly (p less than 0.001) decreased from 154 +/- 38 to 117 +/- 26 msec during angiotensin infusion. Peak early diastolic mitral inflow velocity (peak E) and the time-velocity integral of E wave (Ei) were significantly decreased during angiotensin infusion from 51 +/- 10 to 45 +/- 11 cm/sec (p less than 0.002) and from 7.47 +/- 1.96 to 5.70 +/- 1.66 cm (p less than 0.001), respectively.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1495170 TI - Prediction of surgical result of valve replacement for chronic isolated mitral regurgitation--the significance of preoperative estimation of postoperative left ventricular afterload. AB - Left ventricular (LV) afterload increases after mitral valve replacement, thus it would be useful to estimate postoperative LV afterload before surgery. We tested the usefulness of an index, wall stress, obtained from preoperative end-diastolic LV dimensions and diastolic blood pressure which would represent LV afterload after surgery. The data were compared with surgical mortality and morbidity. The wall stress ranged from 98 to 220 kdynes/cm2 and was 202 or higher in 3 patients who died. Five patients had wall stress above 200 kdynes/cm2. Among these, intra aortic balloon pumping (IABP) was used in 4, and 3 died. Prolonged catecholamine support for greater than 10 days was given to all of the 4 patients, including two who died 14 and 23 days after surgery. Among 38 patients who had wall stress less than 200 kdynes/cm2, none died, IABP was performed in 3 patients, and prolonged catecholamine infusion was required in 5 patients. The incidence of mortality and morbidity were significantly higher in the high stress than in the low stress group (Chi-square analysis). Left ventricular end-diastolic index was larger in the high stress than in the low stress group (p less than 0.05). The mass/end-diastolic volume ratio was smaller in the high stress group than in the low stress group (P less than 0.05). In conclusion, this new index, predictive wall stress, is useful in selecting patients who would have high mortality and morbidity. PMID- 1495171 TI - [Adrenal catecholamine releases during hypotension with continuous administration of calcium entry blockers and nitroglycerin]. AB - We investigated the effect of nicardipine and diltiazem on adrenal catecholamine releases, and compared it with the effect of nitroglycerin in dogs. A 35% reduction in mean arterial pressure was achieved and maintained for 45 minutes. The dogs were observed until 60 minutes after the discontinuation of drug infusions. Adrenal catecholamine releases increased during hypotension with continuous administration of nicardipine, diltiazem and nitroglycerin, but they showed no significant differences between each drug. There was no more increase in adrenal catecholamine releases in spite of additional nicardipine administration. These results suggest that Ca2+ antagonist such as nicardipine directly inhibits the catecholamine releases from the adrenal glands. PMID- 1495172 TI - [Differences of regional blood flow after stellate ganglion block with local anesthetic and that after stellate ganglion resection using ultrasonic Doppler flowmeter]. AB - Ten mongrel dogs were divided into two groups; stellate ganglion block (SGB, n = 5) group and stellate ganglion resection (SGR, n = 5) group. Anesthesia was induced with pentobarbital 25 mg.kg-1. The animals were mechanically ventilated to maintain a constant PaCO2 (35-40 mmHg). Left common carotid arterial flow (CCAF), left external carotid arterial flow (ECAF), left vertebral arterial flow (VAF) and left brachial arterial flow (BAF) were measured using an ultrasonic transit time flowmeter. Internal carotid arterial flow (ICAF) was calculated by subtracting ECAF from CCAF. After thoracotomy, the first SGB with 0.5% mepivacaine 1.5 ml or SGR was performed. Ninety minutes after the first SGB, the second SGB was performed. The data were taken for 180 minutes after the first SGB or SGR. In SGB, CCAF and BAF increased significantly for the duration of action of local anesthetic. But VAF and ICAF increased significantly for a short time after the block. In SGR, CCAF, BAF and ICAF increased significantly during the experiment. But VAF showed a transitory increase immediately after the resection. The authors conclude that sympathetic ganglion block with local anesthetic should be performed repeatedly when increase of blood flow in blood vessels with strong autoregulation from the brain is anticipated. PMID- 1495174 TI - [The effect of epidural analgesia on respiratory muscles]. AB - The effect of epidural analgesia on respiratory functions and muscular power was studied in patients. The subjects had no abnormality of cardiopulmonary system, and were classified into two groups; the adult group whose ages were 21 to 59, and the aged group, 60 to 72. Either 1% or 2% mepivacaine for epidural anesthesia was used to obtain the analgesic level up to Th4 and Th7 in adult group, and Th4 in aged group. The analgesic level was assessed by the pin-prick method. Vital capacity, forced vital capacity, forced expiratory volume 1 second, peak expiratory flow rate, maximal mid-expiratory flow rato, maximal inspiratory pressure and maximal expiratory pressure decreased significantly after epidural anesthesia in all patients whose analgesic levels were up to Th4. In all patients, the change of maximal expiratory pressure was larger than that of maximal inspiratory pressure after epidural analgesia. The patients whose analgesic levels were up to Th7 by 1% mepivacaine in adult group, showed a significant increase of maximal inspiratory pressure. It is concluded that epidural anesthesia diminishes respiratory functions and respiratory muscular power associated with a higher level of analgesia. PMID- 1495173 TI - [Anesthesia and postoperative stroke in patients with previous cerebrovascular disease]. AB - A retrospective study was performed to determine the incidence of perioperative stroke in patients with previous history of cerebrovascular disease (CVD). One hundred and seventy eight out of 20048 patients who underwent anesthesia and surgery during the period of 1985 to 1989 had history of prior CVD. Of them, 137 patients were managed with general anesthesia and 41 with regional anesthesia. Factors analyzed were interval between the prior CVD and the operation, intraoperative hemodynamic changes, perioperative changes in the hematocrit and urinary output, and postoperative neurological complications. Postoperative neurological complications occurred in 31 of the patients given general anesthesia (delayed awakening in 26, dementia syndrome in 6 and deterioration of paralysis in 1), whereas only one patient developed dementia syndrome postoperatively in those given regional anesthesia. None of the patients developed a postoperative stroke. There was no direct relationship between the factors analyzed and the incidence of postoperative neurological complications. Further studies are needed to identify more precisely factors contributing to the occurrence of cerebrovascular complication in a high risk patients. PMID- 1495175 TI - [Effects of prostaglandin E1 and epidural block on circulatory, hepatic and renal functions during anesthesia for major upper abdominal surgeries]. AB - The effects of low dose (0.02 microgram.kg-1.min-1) prostaglandin E1 (PGE1), epidural block (EP) or combination of PGE1 and EP (PGE1 + EP) under general anesthesia on circulatory, hepatic and renal functions were studied in 31 patients undergoing major upper abdominal surgeries without hepatic or renal dysfunction preoperatively. Mean arterial pressure decreased by 10% in PGE1 and EP groups, while 20% in PGE1 + EP group. Cardiac output decreased significantly in EP group, increased in PGE1 group and was unaltered in PGE1 + EP group during anesthesia and the operation. The arterial ketone body ratio as a hepatic function test increased following the administration of PGE1 or epidural block. Urine output, osmotic clearance and free water clearance were higher in PGE1 + EP group during the operation. These results suggest that the combination of low dose PGE1 and epidural block maintain cardiac output and organ blood flow during anesthesia and surgery in spite of a greater decrease in arterial blood pressure. PMID- 1495176 TI - [Comparison of continuous epidural fentanyl and morphine for postoperative pain management after upper abdominal surgery]. AB - Fentanyl and morphine were administered epidurally to the patients after upper abdominal surgery for postoperative pain management. One hundred and ninety patients were divided into 3 groups; F group: bolus and continuous administration of fentanyl, M group: bolus and continuous administration of morphine, FM group: bolus of fentanyl and morphine and continuous administration of morphine. Pain scores of 1, 2, 3, 4, 8, 12 hours after administration and of the next morning were examined and side effects were recorded. Pain scores at 1 and 2 hours in F and FM group were significantly lower than those in M group. There were no significant differences in the scores among 3 groups from 3 hours to the next morning. The incidence of itching in F group was significantly less than in other groups. Respiratory depression (less than respiratory rate 8.min-1) occurred in 2 cases in M and FM group, but no case in F group. FM group had no advantage compared with F group. We conclude that continuous epidural infusion of fentanyl is more useful than morphine for postoperative pain management after upper abdominal surgery. PMID- 1495177 TI - [Amnesic effect of oral midazolam as premedication in children]. AB - We evaluated the sedative and amnesic effects of oral midazolam as premedication in children. Sixteen children, aged 4-12 yr, undergoing elective minor surgery were divided into 2 groups. One group received midazolam 0.5 mg.kg-1 with atropine 0.03 mg.kg-1 orally. The other control group received only atropine 0.03 mg.kg-1. There was no significant difference in the sedative scale at induction between the 2 groups. Doll-recall was used to assess the amnesic effects. In the midazolam group, 75% of the children forgot dolls they had seen on entering the operating room. Midazolam produced significant anterograde amnesia but no retrograde amnesia. This result suggests that children who received midazolam as premedication forget unpleasant memories at induction and their postoperative emotional responses are least influenced by their memories. We conclude that oral midazolam 0.5 mg.kg-1 is an effective preanesthetic medication in children. PMID- 1495178 TI - [Epidural midazolam with bupivacaine--optimal dose for postoperative pain relief]. AB - Optimal dose of epidural midazolam with bupivacaine for postoperative pain relief was investigated. Forty seven patients for upper abdominal surgery were divided into 5 groups. Each group had either 0.25% bupivacaine 6 ml (control group), 0.25% bupivacaine 6 ml + midazolam 0.025 mg.kg-1 (0.025 group), 0.05 mg.kg-1 (0.05 group), 0.075 mg.kg-1 (0.075 group), or 0.1 mg.kg-1 (0.1 group) administered epidurally for complaint of first postoperative pain. Blood pressure (BP), heart rate (HR), respiratory rate (RR) and sedation score (SS) were monitored for 120 minutes, and the time interval for next analgesics (TNA) was checked. In each group, BP fell down 10 minutes after injection, HR was unchanged, and RR (except for 0.1 group) decreased, compared with the preinjection level. There was no difference between control group and others in BP, HR and RR. But 3 cases in 0.075 group and 4 cases in 0.1 group needed chin lift with a pillow under the shoulder for slight airway obstruction. The most optimal SS was obtained in 0.05 group. TNA was significantly longer in 0.025 and 0.05 groups than in the control group. It was concluded that the optimal dose of epidural midazolam with 0.25% bupivacaine 6 ml was 0.05 mg.kg-1 for postoperative pain relief after an upper abdominal surgery. PMID- 1495179 TI - [Effects of hypothermia with cardiopulmonary bypass on posterior tibial nerve somatosensory evoked potentials in man]. AB - Somatosensory evoked potential after posterior tibial nerve stimulation (PTN SEP), as well as nasopharyngeal, bladder and plantar temperature were recorded in ten patients during cardiac surgery with hypothermic cardiopulmonary bypass. There was a best negative correlation between latencies (P27, P40 and the interpeak latency between P40 and P27 (P40-P27)) and nasopharyngeal temperature, but no correlation was found between latencies and plantar temperature during cooling and rewarming (27-37 degrees C) with cardiopulmonary bypass. No correlation was found between changes in amplitude and temperature. The slope of linear regression line of latencies versus nasopharyngeal temperature was -1.05 msec.degrees C-1 for P27 (r = -0.93), -1.47 msec.degrees C-1 for P40 (r = -0.95) and -0.43 msec.degrees C-1 for P40-P27 (r = -0.78). This study suggests that nasopharyngeal temperature measurement is required to aid the interpretation of PTN-SEP changes during hypothermia. PMID- 1495180 TI - [The influence of infusion volume on hemodynamics during experimental laparotomy]. AB - The influence of infusion volume on hemodynamics was studied in adult mongrel dogs undergoing laparotomy. Study 1: Total blood volume (TBV) was measured in 5 dogs undergoing laparotomy without fluid administration for 180 min. TBV before surgery was 71.2 +/- 10.7 ml.kg-1 and remarkably decreased to 59.9 +/- 11.5 ml.kg 1, at a rate of 3.8 ml.kg-1.h-1. Study 2: 21 dogs were divided into 3 groups. Group C had restricted fluids during the study. Group I had infusion of lactated Ringer's solution (LR) at a rate of 10 ml.kg-1.min-1 and Group II at a rate of 20 ml.kg-1.min-1 for 180 min. In group C, mAP and HR were unchanged but CVP, cardiac output, renal blood flow (RBF) and skin blood flow decreased after laparotomy. On the other hand, CVP and RBF were maintained until 180 min in Group I. In Group II, though the hemodynamic parameters were well maintained and urine output was maximal, Ht, Na, concentration and especially plasma colloid osmotic pressure (Pcop) decreased. These results suggest that administration of LR at a rate of 20 ml.kg-1.min-1 is rational to prevent the decrease of TBV and to maintain the peripheral circulation during the surgical procedure, but it may decrease Pcop. PMID- 1495181 TI - [The effects of 20% saline solution on the circulatory dynamics during the hemorrhagic shock state]. AB - This experiment was performed to study the effects of administration of 20% saline solution 1.5 ml.kg-1 on the circulatory dynamics during the hemorrhagic shock state. Administration of 20% saline solution 1.5 ml.kg-1 during the hemorrhagic shock produced twofold increase of the mean arterial blood pressure for one hour, 2.5 fold increase of the cardiac output, increasing tendency in the mean pulmonary arterial pressure, central venous pressure, and the heart rate, accompanied by decrease in total peripheral resistance and the pulmonary blood vessel resistance. There were no improvements in acidosis and hematocrit. These data suggest that the circulatory improvements after the administration of 20% saline solution depend on an increase in cardiac output as the result of improvements in both pre- and after-load, but not of plasma volume expansion. The results also suggest that the administration of 20% saline solution 1.5 ml.kg-1 is useful for an emergency case with acute circulatory insufficiency or for emergency resuscitation. PMID- 1495182 TI - [Perioperative renal functions in patients with chronic renal disease]. AB - Renal function was studied in patients with compensated renal failure and in those with slight renal disorder during and after operations focusing on several aggravating factors. After perioperative episodes of hypovolemia, bleeding and shock, the levels of urine beta 2 microglobulin and FENa were elevated, showing the abnormal renal tubule functions. Elevation of NAG and the decrease of Ccr were observed, showing the organic damage on the renal tubular cell and the influence on GFR. These aggravating factors should be eliminated to prevent the irreversible renal changes. PMID- 1495183 TI - [Thrombelastography as a bedside monitor of coagulation and fibrinolysis during surgery--a report of three cases]. AB - Three patients with abnormal hemostasis during surgery were reported. They were monitored by thrombelastography (TEG). The first case was a 48 year old male who underwent extravivo hepatectomy. TEG showed hypo-coagulability during anhepatic phase. After reperfusion to the liver, the coagulability determined by TEG returned to a normal pattern. The second patient was a 32 year old female who underwent laparotomy to stop bleeding for cervico-vaginal laceration after delivery. The patient had been in severe hemorrhagic shock, and massive blood transfusion and fluid administration were performed. TEG showed remarkable hypocoagulability probably due to blood dilution and consumption coagulopathy. When TEG returned to a normal pattern after administration of fresh frozen plasma and fresh whole blood, the abnormal bleeding stopped. The third patient was a 48 year old male who underwent resection of metastatic brain tumor. He had hepatocellular carcinoma and liver cirrhosis. During surgery, abnormal bleeding was seen at surgical field, when TEG revealed remarkable hyper-fibrinolysis. After antifibrinolytic therapy coupled with replacement therapy, TEG returned to a normal pattern and the abnormal bleeding ceased. We conclude that TEG is a useful bed side monitor for the diagnosis of coagulopathy and hyper-fibrinolysis during surgery. PMID- 1495185 TI - [A disposable tracheal spray device for patients in whom it is difficult to indwell a urinary catheter]. AB - A disposable tracheal spray device was utilized for 20 patients in whom it was difficult to indwell a urinary catheter in the past 4 years. Among them, 18 patients were successfully inserted with a Foley catheter after sufficient lubrication of whole urinary tract with lidocaine using this device. In one patient for gastrectomy, it was not possible to insert because of obstruction of the urinary tract at the prostate. Another patient showed abnormal urinary tract with normal urination. There were no major complications by this manipulation. It was concluded that this application could provide useful informations about the urinary tract in the patients with difficulty for insertion of the urinary catheter, and it provides sufficient lubrication for the indwelling. PMID- 1495184 TI - [Perioperative management for type A acute aortic dissection]. AB - Twenty nine cases of type A acute aortic dissection were subjected to a retrospective study concerning perioperative management. Two keys pointed out for the management were as follow; (1) An optimal control of blood pressure is the most important measure to avoid advance of aortic dissection or rupture of dissecting aneurysm. Both pericardiac tamponade and aortic valve insufficiency should be taken care of from their onset, since they are often complicated after aortic dissections and their onset is fatal. (2) Separated brain perfusion and profound hypothermia with total circulatory arrest might involve a high risk of inducing postoperative brain damage and mortality, especially for old patients. PMID- 1495186 TI - [Anesthetic management of a neonate with esophageal atresia with double tracheoesophageal fistulae]. AB - We reported the anesthetic management of a 1-day-old female neonate (2,110 gm) with esophageal atresia combined with double tracheoesophageal fistulae, which is classified as Gross type D. Though Gross type C was suspected preoperatively, the proximal fistula was found coincidentally during the preparation of the upper pouch. Because, for one thing, the origin of the proximal fistula was close to the end of the upper pouch (1cm), and for another, the distance between the both fistulae was short (1cm). As for the proximal fistula, it was 2 mm in diameter, and it was easily sealed with the side of the endotracheal tube. No other respiratory managements were needed except frequent suctionings of copious intratracheal secretions. On the other hand, the distal fistula, 10 mm in diameter, caused hypercapnea due to hypoventilation before gastrostomy. It was so big that it is easily intubated. This type of tracheoesophageal fistula is extraordinarily rare and its proximal fistula is difficult to find before, during, and even after operation. The missing of the proximal fistula often provokes severe respiratory infections and furthermore, sepsis postoperatively. It is concluded that in all the cases of tracheoesophageal fistula, the existence of the proximal fistula should be considered without fail and managed accordingly. To diagnose correctly, the use of preoperative bronchofiberscopy is also recommended. PMID- 1495187 TI - [Anesthesia for cesarean section in a patient with Ebstein's anomaly]. AB - A 30-year-old woman with Ebstein's anomaly was scheduled for Cesarean section at 38 week gestation because of latent fetal distress. After arterial and central venous catheters were inserted, general anesthesia was started. Anesthesia was induced smoothly and rapidly through intravenous route. Following induction, her hemodynamics was stable until post-operative period. The baby weighed 1564g and had an Apgar score of 8 at 1 minute. A patient with Ebstein's anomaly during pregnancy and anesthesia has potential for a variety of hemodynamic disturbances. This case illustrates the importance of careful attention to the preoperative findings and the perioperative hemodynamic parameters. PMID- 1495188 TI - [The anesthetic management for adrenalectomy of a patient with Cushing's syndrome in pregnancy]. AB - The anesthetic management for left adrenalectomy of a pregnant patient with Cushing's syndrome caused by adrenal adenoma during pregnancy was reported. At 21 week gestation, anesthesia was induced with modified NLA and maintained with nitrous oxide-enflurane-oxygen combined with continuous lumbar epidural anesthesia. Postoperatively, she was delivered a normal, 1990 g infant at 37 week gestation. The present case is believed to be the first reported case of general anesthesia in detail for adrenalectomy in a patient with Cushing's syndrome during pregnancy. The anesthetic management including choice of anesthetics, anesthetic method, intraoperative monitoring, influence of catecholamine, and fetal as well as maternal complication was reviewed from literatures. PMID- 1495189 TI - [Use of diltiazem in the anesthetic management of epinephrine predominant pheochromocytoma]. AB - This report describes a case of epinephrine predominant pheochromocytoma successfully managed intraoperatively with an infusion of diltiazem. A 50-yr-old woman with a 10-yr history of diabetes mellitus was admitted to the hospital because of thirst and general fatigue. A cystic left adrenal tumor was found on computed tomographic scan. Although resting plasma catecholamine levels were normal, plasma norepinephrine and epinephrine levels obtained from the left adrenal vein were 1.6 ng.ml-1 (normal, 0.04-0.35) and 6.2 ng.ml-1 (normal, less than 0.12), respectively. Diltiazem was administered i. v. at a rate of 3 micrograms.kg-1.min-1 before induction of anesthesia. Anesthesia was induced with enflurane 2-3% and nitrous oxide in oxygen, followed by tracheal intubation facilitated with vecuronium. Anesthesia was maintained with enflurane 1-3% and nitrous oxide in oxygen. Paralysis was maintained with vecuronium. Hypertension during the manipulation of the tumor was controlled by increasing the inspired concentration of enflurane or by increasing the infusion rate of diltiazem to 5 micrograms.kg-1.min-1. There was no tachyarrhythmia. The infusion of diltiazem was continued until the draining vein from the tumor had been ligated. Hypotension, after removal of the tumor, was treated by the rapid infusion of fluid. Plasma norepinephrine and epinephrine levels during tumor manipulation were 1.18 ng.ml-1 and 6.57 ng.ml-1, respectively. PMID- 1495190 TI - [The factors that influence intraoperative blood loss during total hip replacement]. AB - Fifty cases of total hip replacement performed by one surgeon were reviewed to compare the effects of epidural and general anesthesia. The blood pressure in patients under epidural anesthesia was significantly lower (P less than 0.001; t test). There was a highly significant correlation between the operation time and the intraoperative blood loss (P less than 0.005, r = 0.67). A significant correlation was noted between the blood pressure and the minute loss of blood (P less than 0.01, r = 0.43). It is concluded that epidural anesthesia is to be recommended rather than general anesthesia in patients undergoing total hip replacement. PMID- 1495191 TI - [Acute pulmonary edema in five patients undergoing sevoflurane anesthesia]. AB - Four adults and a child undergoing surgery with sevoflurane anesthesia developed acute pulmonary edema immediately after anesthesia. Prior to development of pulmonary edema all patients exhibited severe arterial hypertension and tachycardia. Their episodes of circulatory changes were, we believed, caused by the local injection of epinephrine for hemostasis in 2 patients (9 y.o. child, 45 y.o. man) and the intrusion of painful surgical stimuli in one patient (67 y.o. man). Circulatory changes in these three patients were treated by increasing the inspired sevoflurane concentration. We, however, speculate that the increase in inspired sevoflurane decreased the cardiac output and that the resulting increase in pulmonary wedge and capillary pressures was caused by an abrupt increase of arterial blood pressure, followed by a rapid increase in afterload due to cardiac suppression from the high concentration of sevoflurane. In 2 patients (74 y.o. man, 61 y.o. woman) arterial hypertension occurred during endotracheal extubation after sevoflurane anesthesia. Because of fast uptake and elimination of sevoflurane due to a low blood/gas partition coefficient, a fast awakening in the latter 2 patients, may be responsible for the abrupt increase in arterial blood pressure. In conclusion, it should be noted that pulmonary edema may be involved when severe circulatory changes occur in a patient undergoing sevoflurane anesthesia. PMID- 1495192 TI - [Coronary artery spasm during coronary artery bypass surgery]. AB - We report two cases of coronary artery spasm during coronary artery bypass surgery. As one of the complications during cardiac surgeries, coronary vasoconstriction occurs mainly after coming off cardiopulmonary bypass. The factors responsible for the spasm include high endogenous catecholamine levels due to inadequate anesthesia and hypothermia, exogenous catecholamines for circulatory support, various chemical mediators and combination of these factors. Coronary artery spasm was suspected strongly because of sudden ischemic change in electrocardiography and simultaneous aggravation of circulatory parameters, which improved immediately after direct injection of coronary vasodilators into vein graft. This method, popular in coronary angiography and catheterization, is effective for release of coronary-artery spasm observed particularly after cardiopulmonary bypass. Then mechanical circulatory assist is readily available to treat possible systemic side effect of the vasodilators. PMID- 1495193 TI - [Synergistic action of cefodizime with other antimicrobial agents on clinically isolated microorganisms. II. Synergistic action with sisomicin]. AB - Cefodizime (CDZM) possesses a broad antimicrobial spectrum and a relatively long half life in the blood. In addition, it shows excellent therapeutic efficacies in the treatment of infections in leukopenic animal models, hence it is expected that CDZM may have good efficacies against various infections in immunocompromised hosts. In the meantime, sisomicin (SISO) not only has strong antibacterial activities against Gram-negative rods (GNR), but has relatively low nephrotoxicity and ototoxicity. Thus, we examined antibacterial effectiveness of the combination of CDZM and SISO against clinical isolates in vitro. 1. Antibacterial effects of CDZM+SISO combination were examined using SISO susceptible strains of Escherichia coli, Citrobacter freundii, Klebsiella pneumoniae, Enterobacter cloacae, Serratia marcescens, Proteus vulgaris, Morganella morganii and Pseudomonas aeruginosa. Observations that the combination of the 2 drugs showed FIC indices between less than 0.5-less than 1.0 against most of these strains at SISO concentrations of 1 MIC or sub MIC levels strongly suggested the presence of a synergistic action between the 2 drugs against SISO susceptible strains of GNR. 2. Of the strains tested, 10% of C. freundii, 6.7% of E. cloacae, 63.3% of S. marcescens, 23.3% of P. vulgaris and 18.0% of P. aeruginosa were found to be resistant to SISO, and little synergistic effect of the 2 drugs was observed against these strains. 3. As the synergistic effect of the 2 drugs against GNR was observed against SISO susceptible strains including those which were resistant to CDZM, but not against those strains which were resistant to SISO, it seems reasonable to conclude that the appearance of the synergistic effect between the 2 drugs depends on the activity of SISO. PMID- 1495194 TI - [Pharmacokinetic studies on oral antibiotics in pediatrics. V. A pharmacokinetic study on cefdinir in pediatrics]. AB - A pharmacokinetic study was performed on cefdinir (CFDN, FK482) 5% fine granules for pediatric use, and pharmacokinetic parameters were calculated. 1. Twenty school children were administered orally a dose level of 3 mg/kg of CFDN fine granules either at 30 minutes before meal (14 children) or 30 minutes after meal (6 children). Plasma concentrations and urinary recovery rates of CFDN were measured. Tmax, Cmax, T 1/2 and urinary recovery rate (0-8 hours) following the administration before meal were 2.00 +/- 0.00 hours, 1.14 +/- 0.11 micrograms/ml, 1.63 +/- 0.14 hours and 23.68 +/- 2.92%, respectively, Tmax, Cmax, T1/2 and urinary recovery rate following the administration after meal were 3.67 +/- 0.33 hours, 0.71 +/- 0.06 micrograms/ml, 2.18 +/- 0.16 hours and 21.76 +/- 2.36%, respectively. Earlier Tmax and higher Cmax were observed when the drug was administered before meal than when administered after meal. There was no statistically significant difference between the 2 groups in urinary recovery rates. However, statistically significant difference was found between the 2 groups when the cross-over technique was used in 6 school children. Nineteen younger children (before meal) and 6 younger children (after meal) were administered with the drug in the same way, and several parameters were measured. Tmax, Cmax, T1/2 and urinary recovery rate following the administration before meal were 2.11 +/- 0.11 hours, 0.98 +/- 0.14 micrograms/ml, 1.71 +/- 0.23 hours and 23.60 +/- 1.72%, respectively, Tmax, Cmax, T1/2 and urinary recovery rate following the administration after meal were 3.33 +/- 0.42 hours, 0.47 +/- 0.14 micrograms/ml, 2.35 +/- 0.27 hours and 12.24 +/- 2.02%, respectively. Earlier Tmax, higher Cmax and higher urinary recovery rate were observed when the drug was administered before meal than when administered after meal. Seven infants (before meal) and 8 infants (after meal) were administered with the drug in the same way, and several parameters were measured. Tmax, Cmax, and T1/2 following the administration before meal were 4.00 +/- 0.62 hours, 0.61 +/- 0.13 micrograms/ml and 3.14 +/- 0.62 hours, respectively, Tmax, Cmax and T 1/2 following the administration after meal were 3.75 +/- 0.25 hours, 0.79 +/- 0.13 micrograms/ml and 2.44 +/- 0.42 hours, respectively. These was no statistically significant difference between the 2 groups. 2. Twenty one school children were administered orally with CFDN fine granules at 30 minutes before meal ata dose level of either 3 mg/kg (14 children) or 6 mg/kg (7 children). Plasma concentrations and urinary recovery rate of CFDN were measured.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1495195 TI - [The influence of cefdinir on the intestinal bacterial flora]. AB - The influence of cefdinir (CFDN), a new oral cephalosporin, on the intestinal bacterial flora was studied in tetra-contaminated mice and in pediatric patients. CFDN in fine granules was administered at a dose of 10 mg/kg once a day for 5 consecutive days to mice contaminated with 4 different species of organism: Escherichia coli, Enterococcus faecalis, Bacteroides fragilis and Bifidobacterium breve. No remarkable changes were observed in the fecal viable cell counts except that decreases in E. coli counts were observed on the day 3 to 5 after starting administration. The subjects in pediatric study were 7 children with infections, 3 boys and 4 girls, with their ages from 6 months to 12 years 7 months. Their body weights ranged from 5.5 to 29.2 kg. CFDN fine granules was administered at each dose of 3.0 mg/kg to 3.7 mg/kg, 3 times a day for 4 to 14 days. During the administration of CFDN, some variations were observed in the pattern of changes in the fecal bacterial flora between subjects. Although Enterobacteriaceae and total counts of anaerobes were markedly decreased in 2 cases, total counts of aerobes were unchanged in the 2 cases, whereas main aerobes and anaerobes except enterococci hardly varied in the other cases. There was no case in which glucose non-fermenting Gram-negative rods and fungi became predominant species continually. Although Clostridium difficile and C. difficile D-1 antigens were detected in 1 and 4 cases, respectively, no relationship was found between the number of C. difficile and the characteristics of the feces. With regard to the drug sensitivities of bacteria isolated from feces before and after administration of CFDN, higher levels of resistance were found in some bacteria such as Enterococcus and Bacteroides during or after administration than before administration. CFDN was detected in fecal samples from 2 cases during administration with concentrations ranging between 0.99-254 micrograms/g. High value of CFDN was found in a case with low beta-lactamase activity in feces, in which marked decrease of Enterobacteriaceae and total counts of anaerobes was observed. The above results suggest that CFDN is considered to be a drug with relatively small influence on the intestinal bacterial flora. But as high concentrations of drugs were detected in feces under some circumstances, our attention will be required. Particular care is also required for the occurrence of diarrhea and microbial replacement during continuous, long-term administration of the drug. PMID- 1495196 TI - [Bacteriological, pharmacokinetic and clinical studies of 5% and 10% granules of cefdinir in the pediatric field]. AB - Bacteriological, pharmacokinetic and clinical studies on cefdinir (CFDN, FK482), a new oral cephalosporin, 5% and 10% granules, were performed in the field of pediatrics. The results are summarized below. 1. Antibacterial activities Antibacterial activities of CFDN against Staphylococcus aureus, Streptococcus pyogenes, Streptococcus pneumoniae, Haemophilus influenzae, Branhamella catarrhalis, Escherichia coli and Klebsiella pneumoniae were studied in comparison with those of cefaclor (CCL), cefixime (CFIX) and amoxicillin (AMPC). MIC80's of CFDN against S. aureus, S. pneumoniae, S. pyogenes, H. influenzae, B. catarrhalis, K. pneumoniae and E. coli were 0.78, 0.20, less than or equal to 0.025, 0.39, 0.10, 0.20 and 0.10 micrograms/ml, respectively. These results show that CFDN has high antibacterial activities against these organisms. MIC80's of CFDN against Gram-positive bacteria were similar to those of AMPC, and was lower than those of CCL and CFIX. As for antibacterial activities against Gram-negative bacteria (GNB), the MIC80 of CFIX against H. influenzae was 0.05 micrograms/ml, which was slightly lower than that of CFDN. THe MIC80's of CFDN against other GNB were similar to those of CFIX. 2. Absorption and excretion Blood concentrations and urinary excretion rates of CFDN 5% and 10% granules and 100 mg capsule were determined. The data on CFDN 10% granules were similar to those on CFDN 5% granules. At a dose of 3 mg/kg, peak blood concentrations (Cmax's) of CFDN ranged from 0.20 to 2.12 micrograms/ml with 5% granules and from 0.50 to 1.15 micrograms/ml with 10% granules at 2 to 3 hours after dosing. At a dose of 6 mg/kg, peak concentrations were 0.66-2.06 micrograms/ml and 0.70-1.52 micrograms/ml with 5% granules and with 10% granules, respectively. At 8 hours after dosing, blood concentrations were 0.04-0.54 micrograms/ml at 3 mg/kg and 0.06-0.27 micrograms/ml at 6 mg/kg. Blood half-lives were 1.33-4.36 hours at 3 mg/kg and 1.14-3.27 hours at 6 mg/kg. AUC's were 1.7-11.0 micrograms.hr/ml with 3 mg/kg and 2.4-8.7 micrograms.hr/ml with 6 mg/kg. With administration of single 100 mg capsule, Cmax's, blood concentrations after 8 hours, T1/2's and AUC's were 0.79-1.88 micrograms/ml, 0.20 micrograms/ml, 1.54-2.72 hours, and 5.2 micrograms.hr/ml, respectively. Urinary recovery rates in the first 8 hours ranged from 6.85 to 39.2% with 3 mg/kg and 6.08-25.5% with 6 mg/kg.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1495197 TI - [Pharmacokinetics and clinical effects of cefdinir 10% fine granules in pediatrics]. AB - Cefdinir (CFDN), a newly developed oral cephalosporin in a 10% fine granular form, was administered to 8 children and concentrations of the drug in plasma and urine and urinary recovery rates of the drug were determined. The subjects were divided into 2 groups of 4 children each; one group received 3 mg/kg of CFDN at 1 hour before meal (in the fasting state), and the other, at 30 minutes after meal. To study clinical and bacteriological effects of this drug, a mean dose of 4.8 mg/kg t.i.d. was administered for 8 days on the average to 9 children with various infections; tonsillitis (3 cases), acute bronchitis (1), pneumonia (1), acute purulent otitis media (1), urinary tract infection (2), and impetigo (1). MICs were determined for 6 drugs including CFDN, cefaclor, cefixime (CFIX), methicillin, cloxacillin, amoxicillin (AMPC) against 4 strains freshly isolated from children receiving CFDN. An inoculum size of 10(6) cfu/ml was used in the MIC-determinations. Adverse reactions and abnormal laboratory findings attributable to this drug were also examined in these children. The results obtained are summarized as follows. 1. Mean plasma peak levels of CFDN were observed at 2 hours after administration in the before-meal group and 4 or 5 hours after administration in the after-meal group mean peak values of 0.88 and 0.50 micrograms/ml, respectively. Mean half-lives were 1.61 hours in the before meal group and 2.54 hours in the after-meal group, and mean AUCs were 4.24 in the former and 3.59 micrograms.hr/ml in the latter. 2. Mean urinary peak concentrations of CFDN were observed during 2-4 hours after dosing in the before meal group and during 6-8 hours in the after-meal group with values of 93.3 and 44.8 micrograms/ml, respectively, in cases for which plasma concentrations of drugs were determined. Mean urinary recovery rates during the first 8 hours after administration in the before- and after-meal groups were 16.6 and 13.4%, respectively. 3. Good clinical effects were obtained with an efficacy rate of 100% in 9 patients with 6 diseases due to bacterial infections. 4. Good bacteriological effects were also obtained against 2 strains of Streptococcus pyogenes, 2 strains of Escherichia coli and 1 strain of Haemophilus influenzae with an eradication rate of 100%. In 3 cases of these and another case (normal flora), strains present before the study were replaced by other strains.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1495198 TI - [Microwave therapy for diseases of the genitourinary organs]. AB - Microwave energy had become a valuable component in the electromagnetic spectrum. Because of its unique energy source, the microwave radiation can penetrate several centimeters into biologic tissue. The energy is absorbed and converted into heat within the tissue. Clinical applications of microwave irradiation fall into two categories; thermotherapy and hyperthermia. Microwave therapy has generated great interest in the field of urology because of its safety, efficiency, and its simplicity as a surgical tool. This review analyses the fundamentals of the science of microwave energy as a therapy and presents an in depth discussion of its theoretical principles, unique characteristics, appropriateness of application, and its potentiality as a long-term modality for the treatment of urologically-related diseases. PMID- 1495199 TI - [The limits of recovery in hydronephrosis. An experimental pathological study]. AB - The object of this experimental study is to elucidate the limits of recovery in hydronephrosis. Hydronephrosis in the rabbit kidney was made by left ureteric ligation for 1, 2, 3 and 4 weeks, followed by relief of obstruction with uretero ureteric anastomosis. Two and 4 weeks after relief, histopathological examination was performed. In proportion to the obstructive period, both proximal tubule and thin portion of Henle's loop showed atrophy of epithelial cells, multi-laminar thickening of basement membranes, and splitting between epithelium and basement membranes. The interstitium showed edema and subsequent fibrosis. These damages were thought to be due to severe ischemia, which such tubules did not recover and even showed more advanced damages after relief. On the other hand, thick portion of Henle's loop, distal tubule and collecting duct showed advanced compression atrophy and dilated lumen, while no severe ischemic damage was demonstrated. Therefore, after relief, they showed recovery, and, even in the case of no recovery, they showed no advanced damages. In hydronephrosis, severe ischemic damages brought about a loss of the ability of recovery. PMID- 1495200 TI - [Growth inhibitory effect of a new anticancer antibiotics, kazusamycin A, on human transitional cancer cell lines in vitro]. AB - Kazusamycin A (KZMA) is a new anticancer antibiotic, which has been proven to have strong anticancer effect and several characteristic features different from currently available anticancer antibiotics. However, there has as yet been no report which had concerned itself with the effect of KZMA on urological cancer. This study was undertaken to determine the inhibitory effects of KZMA on transitional cancer cells in vitro, the augmentation of the inhibitory effect by combining thermal treatment and the effect of KZMA upon DNA distribution. Human transitional cancer cells, KU-1, and T-24 were used as targets. Fifty % inhibitory concentration of KZMA was determined after these cells were exposed to graded concentrations of KZMA for 2 to 48 hours, and to the concentration of KZMA for 2 hours at the temperature of 42 degrees C. Viable cells were counted by dye exclusion assay (DEA) and by tetrazolium-based colorimetric assay (MTT-assay) exposure. KZMA inhibited the growth of the three transitional cancer cells strongly and this inhibitory effect appeared to be depend upon the exposure time and the concentration of KZMA. IC50s after 2-hour exposure at the temperature of 42 degrees C was shown to be decreased to 23 to 87% of that at the temperature of 37 degrees, indicating an augmentation of the inhibitory effect of KZMA by combining thermal treatment. MGH-U1 was the most sensitive to the combination of KZMA and hyperthermia. The cell cycle analysis showed that KZMA had G2-arresting and M-retarding effects, which were different compared with currently available anticancer antibiotics.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1495201 TI - [Histopathological study of metallothionein in bladder cancer and renal cell carcinoma]. AB - Metallothionein (MT) is a low molecular-metal binding protein with multiple biological functions. Recently, MT has been implicated as a factor involved in resistance to anticancer drugs, which presumably inactivates anticancer drugs, including cisplatin, and doxorubicin. In this report, we investigated the relationship of MT expression with the clinical features in bladder cancer and renal cell carcinoma. In 35 cases of bladder cancer, 10 cases of renal cell carcinoma and 3 cases of normal mucosa of bladder, the expression of MT was immunohistologically examined by avidinebiotin-peroxidase (ABC) staining of paraffin-embedded tissue specimens with anti-MT antibody. Intense MT expression was noted in all cases of normal mucosa of bladder. MT was detected in 10 of 35 cases of bladder cancer, with the incidence of MT expression being significantly higher increases with lower pathological tumor grade. MT was detected in 8 of 10 cases of renal cell carcinoma, and all of the their normal renal tubules showed more intense staining. A number of hypotheses can be proposed from these observations. First, our observation of decreased MT expression in poorly differentiated carcinomas, which are the more proliferating tumors, this suggests correlation of MT expression with proliferative status of cancer. Second, the higher incidence of MT expression in renal cell carcinoma than in bladder cancer may suggest that it is a factor responsible for the lower efficacy of chemo therapy in renal cell carcinoma than in bladder cancer. PMID- 1495202 TI - [Immunological study of induction of metallothionein in bladder cancers]. AB - Metallothionein (MT) in tumor cell has been indicated as one of the factors involved in the mechanism of resistance to anticancer drugs. The relationship between expression of MT and chemotherapy with anticancer drugs was studied with bladder cancer culture cell lines and tissue samples from clinical cases. In drug resistance cell lines, MT expression was studied by immunohistological staining of the avidin -biotin peroxidase complex (ABC) method, and by the radioimmunoassay (RIA) method, using an anti-MT antibody. As for tissue samples from clinical cases, 114 paraffin embedded samples of 29 cases before and after chemotherapy were subjected to immunohistological staining of MT. Human-bladder cancer cell lines with resistance to anticancer drugs (C1-7/CDDP, T-24/ADM) showed increased of expression of MT compared to each parental cell lines (C1-7, T-24), suggesting relationship of resistance to anticancer drugs and MT expression. In the clinical cases, those with continuous administration such as intra-vesicle chemotherapy or oral administration chemotherapy showed greater incidence of positive staining of MT expression in comparison with cases with fewer administrations, such as intra-arterial infusion therapy or intravenous administration chemotherapy. These results demonstrated that repetitive and continuous administration of anticancer drugs cause increase of MT in bladder cancer cell, which may be a possible mechanism of acquired resistance to anticancer drugs. PMID- 1495203 TI - [Recurrence following surgery for primary renal pelvic and ureter cancer- clinicopathologic analysis of distant metastasis]. AB - A retrospective analysis of 59 patients with renal pelvic and ureter cancer (56 transitional cell carcinomas, 2 squamous cell carcinomas, and 1 adenocarcinoma), which were treated surgically, was performed in relation to postoperative recurrence, particularly distant metastasis. Of the 59 cases, postoperative recurrences developed as distant metastasis in 9 cases (15.3%), as bladder cancer in 19 cases (32.2%) and as contralateral renal pelvic and ureter cancer (bilateral metachronous cancer) in 3 cases (5.1%). Three of the 9 cases with the development of distant metastasis were squamous cell carcinoma or adenocarcinoma, and the others transitional cell carcinoma. All the metastases occurred within 2 years. In cases with transitional cell carcinoma, nonpapillary tumor, grade 3, high stage (pT3 and pT4), positive vascular invasion and IFN beta or gamma had a significant influence on the rate of distant metastasis. On the other hand, location, diversity and previous or coexistent bladder cancer did not seem to be related to the frequency of the development of distant metastasis. Thus, tumor aggressiveness was the only predictive valuable of the development of distant metastasis after surgery for renal pelvic and ureter cancer. PMID- 1495204 TI - [An approach to stoma-less continent urinary diversion by uretero-ileoceco proctostomy (ileocecorectal bladder)]. AB - The current practice of continent urinary diversion still places the patients under the restraint of the stoma and intermittent catheterization. To overcome these problems, we developed a new technique of urinary diversion of which continent is controlled by the anal sphincter. The isolated ileocecal segment is intussuscepted and interposed between the ureters and the rectum. The conjoined ureters are anastomosed to the stump of the ileal limb, and the antimesenteric portion of the cecal limb is joined to the anterior wall of the rectum. The surgical procedure is simpler than that of the continent reservoirs currently employed. The intussuscepted ileocecal segment prevents fecal reflux to the upper urinary tract and may also inhibit carcinogenesis at the uretero-intestinal junction. Additionally, the rectal capacity is augmented by the side to side anastomosis between the cecal limb and the rectum. Our preliminary experience in 10 cases were satisfactory with respect to voiding function, antireflux mechanism of the intussuscepted ileocecal segment and quality of life. The results will justify further trials with this stomaless continent urinary diversion for those in whom the urethra cannot be used. PMID- 1495205 TI - [Results in treatment of urinary incontinence in the elderly]. AB - The diagnosis and treatment of urinary incontinence in the elderly out-clinic patients were reviewed. Sixty-three patients (24 males and 39 females) over 60 years old, who consulted our clinic complaining urinary incontinence, were subjected to the present study. The patients' ages ranged from 60 to 91, with the mean age of 72.9 years old. The types of the incontinence were urge in 44 cases (69.8%), stress in 10 (15.9%), outflow in 5 (7.9%) and mixture of urge and stress in 4 (6.4%). Urge incontinence resulted from unstable bladder in 63.6% and from neurogenic bladder (overactive detrusor) in 36.4%. Cerebrovascular diseases were the most common cause of the neurogenic bladder. Fifty-four patients (85.7%) were out-patients and 9 (14.3%) were hospitalized for other diseases. Thirteen patients (20.6%) with dementia were included. Diagnosis was made on the basis of a detailed questionnaire, physical examination and voiding chart, and confirmed by urodynamic study. Treatment was positively made by means of drug therapy, operation, clean intermittent catheterization and/or behavior training. As results, incontinence disappeared in 52.4% (frequency of incontinence/day: 5.0 +/ 2.6 times/day to 0), was fairly improved in 30.2% (5.1 +/- 2.3 to 1.2 +/- 0.8), was slightly improved in 7.9% (3.4 +/- 1.4 to 2.4 +/- 1.4) and unchanged in 9.5% (8.2 +/- 2.3 to 8.3 +/- 2.2). Severe neurogenic bladder (overactive), dementia and physical disability were proposed to be important factors responsible for treatment failure. Aggressive therapy should be tried to treat the urinary incontinence in the elderly, since favourable results can be expected in most of the cases. PMID- 1495206 TI - [A case of urinary retention due to tuberculous pyometra]. AB - A rare case of urinary retention due to tuberculous pyometra is presented. A 70 year-old woman visited our hospital complaining of dysuria and pollakisuria on January 26, 1990. In spite of medication of cholinergic agents, urinary retention developed on April 6, 1990. Cystoscopy revealed elevation of the urethra and bladder neck. Physical examinations disclosed a child-head-sized tumor in the lower abdomen, which persisted following catheterization. Excretory urogram showed a large retrovesical mass. Chain urethrocystogram revealed anterior dislocation of the bladder neck and the proximal portion of the urethra. CT scan and MRI demonstrated a fluid-filled pelvic mass, which positioned above the vagina and compressed the urinary bladder anteriorly. Total hysterectomy was performed on August 6, 1990. Pathological diagnosis was tuberculous endometritis. Urinary symptoms disappeared immediately after the operation. Postoperative chain urethrocystography revealed complete cure of the dislocation of the bladder neck and urethra. We collected 34 cases of urinary retention due to gynecological disease in Japan, and 110 cases in English literature. Among the frequent diseases were retroverted gravid uterus, prolapse uteri, uterine leiomyomas, ovarian cyst, imperforated hymen and vaginal atresia. The mechanisms of urinary retention in gynecological disease are discussed. No case of urinary retention due to tuberculous pyometra was found in the literature. PMID- 1495208 TI - Concern about paramedics' role in the emergency department. PMID- 1495209 TI - Flumazenil useful in reversing effects of benzodiazepines. PMID- 1495207 TI - [The effectiveness of anal submucosal injection of methotrexate for relapsed prostatic cancer--a case report]. AB - The case is a 77-year-old man who was first examined in August 1980 (at age 67). Prostatic biopsy revealed a poorly-differentiated adenocarcinoma, and clinically, diagnosis was made as stage B. Castration and DES administration were carried out. Subsequent chemotherapy with BLM, MMC, and 5-FU led to CR. A periodical check-up in September 1985 detected a pelvic lymph node metastasis, which was, however, completely remitted by radiotherapy and chemotherapy. In April 1990, local relapse was noted in the left lobe of the prostate. Biopsy revealed a poorly-differentiated adenocarcinoma. Three courses of intravenous administration of CDDP, THP, and VP-16 caused no change. From August 1990 on, anal submucosal injection of MTX was started. 20 mg of MTX administration once a week, for consecutive 5 weeks, followed by 4-week interruption on ambulatory basis formed one course. The tumor was distinctly reduced following one course, disappeared (MRI) following two courses and showed only a few viable cells (biopsy) following four courses. We consider that the present method is a hopeful new therapeutic approach. PMID- 1495210 TI - More on Desert Storm. PMID- 1495211 TI - Sepsis. PMID- 1495212 TI - A 39-year-old nurse with accidental discharge of an epinephrine autoinjector into the left index finger. PMID- 1495214 TI - Decreasing the wait for emergency department patients: an expanded triage nurse role. PMID- 1495213 TI - A 40-year-old woman with an air bag-mediated injury. PMID- 1495215 TI - Darnall Army Community Hospital's response to the Killeen massacre. PMID- 1495216 TI - Recognition of panic disorder in the emergency department. PMID- 1495217 TI - First aid and emergency care at a major-league baseball stadium. PMID- 1495218 TI - Breast cancer: one nurse's inside story. PMID- 1495219 TI - Getting the most from pulse oximetry. PMID- 1495220 TI - Emergency services nursing flow sheet. PMID- 1495221 TI - Emergency department use of facsimile and automatic teller machines. PMID- 1495222 TI - ED gridlock and diversion. Law and the emergency nurse. PMID- 1495223 TI - Children with chickenpox: emergency department care and teaching. PMID- 1495224 TI - Patterns of sharp force injury. PMID- 1495225 TI - A 15-year-old girl with abdominal pain, vomiting, tachycardia, and tachypnea. PMID- 1495226 TI - A look at our new emergency department--St. Luke's Hospitals-Meritcare, Fargo, North Dakota. PMID- 1495227 TI - See you around sometime. PMID- 1495228 TI - [Glucose transport in different physiological situations (development, nutrition, exercise)]. PMID- 1495229 TI - [Risk factors for atherosclerosis in non-insulin-dependent diabetes]. PMID- 1495230 TI - [External and implantable insulin pumps and other techniques in insulin therapy]. PMID- 1495231 TI - [Screening of pre-diabetes type I: Why? How? Whom?]. PMID- 1495232 TI - [Screening of pre-diabetes type I: possibilities and limits]. PMID- 1495233 TI - [Screening of type I diabetes in children]. PMID- 1495234 TI - [Transport and transporters of glucose in different animal models of insulin resistance]. PMID- 1495235 TI - [Investigation of insulin secretion in pre-diabetes type I]. PMID- 1495236 TI - [Prevalence and predictive value of islet cell autoantibodies and anti-glutamic acid decarboxylase in a family study in Lyons]. PMID- 1495237 TI - [HLA 1992 and insulin-dependent diabetes]. PMID- 1495238 TI - [Clinical biochemistry of alcohol and its metabolic and hepatic effects]. PMID- 1495239 TI - [Effects of alcohol drinking in the diabetic in a fasting and fed state: drug interactions]. PMID- 1495240 TI - [Postprandial hypoglycemia and alcohol drinking]. PMID- 1495241 TI - [Is alcohol a risk factor for diabetes or does hyperglycemia predict "alcoholic death"? Analysis of causes of death in the Prospective Parisian Study]. PMID- 1495242 TI - [Autoregulation of carbohydrate recovery in the muscle]. PMID- 1495243 TI - [Psychobiology of the appetite]. PMID- 1495244 TI - [Genetics, dietary management and nutritional adaptations]. PMID- 1495245 TI - [From pharmacology to neurobiology in dietary behavior]. PMID- 1495246 TI - [Sensory qualities of food and their effects]. PMID- 1495247 TI - [Clinical analysis of eating disorders: therapeutic implications]. PMID- 1495248 TI - [Apollinaire Bouchardat Prize 1992. Pancreatic islets transplantation in man: history of one therapeutic strategy]. PMID- 1495249 TI - [Maurice Derot Prize 1992. Insulin dependent diabetes in 1992: should we review our nosological and clinical attitude?]. PMID- 1495250 TI - [Lipid anomalies in NIDDM and insulin resistance. Role of metformin]. PMID- 1495251 TI - [Regulation of cellular transport of glucose and its perturbations in diabetes]. PMID- 1495252 TI - [Role of the glut 2 transporters in the pathogenesis of type II diabetes]. PMID- 1495253 TI - [Gastric motility and sugar diabetes]. PMID- 1495255 TI - Ethics: where to begin? PMID- 1495254 TI - [Physiopathology of diabetes in famine]. PMID- 1495256 TI - Impaired nursing performance: ethical issues. PMID- 1495257 TI - Five years of risk management in Kansas: an overview. PMID- 1495258 TI - The Nursing Community Ethics Project: an ethics education opportunity for Kansas nurses. PMID- 1495259 TI - The gift of sight. PMID- 1495260 TI - AIDS in Kansas. PMID- 1495261 TI - [A new vaccination schedule]. AB - In July 1991 a new vaccination strategy has been recommended. Two alterations are involved; the general recommendation of the pertussis immunization and a second MMR vaccination. Comments are given on BCG-, pertussis-, MMR- and HIB vaccinations. The continued existence or the new foundation respectively of medical advisory boards on immunization problems in all states of the Federal Republic of Germany are strongly recommended. PMID- 1495262 TI - [Current therapy of febrile convulsions]. AB - The author gives a review on clinical features and therapeutic aspects of febrile seizures. The treatment with different anticonvulsants is described. Differentiation between simple and complicated febrile convulsions seem to be useful for therapeutic management. PMID- 1495263 TI - [Kinetics of vaccine antibodies to tetanus toxoid, diphtheria toxoid, measles virus, poliomyelitis virus and pneumococci after allogenic and autologous bone marrow transplantation and booster immunization. 1: The kinetics of vaccine antibodies to tetanus toxoid after allogenic and autologous bone marrow transplantation]. AB - Today BMT belongs to the established methods of treatment in haematology and oncology. Because of the constant increase of healthy long-term survivors after BMT the problem of immunological reconstitution and eventual possible late effects gets more and more importance. One problem, which til now has been few attention paid to, is that of the protection by vaccination after BMT. We report on the kinetics of the tetanus-antitoxin in 20 patients after allogeneic or autologous BMT and demonstrate the influence of a graft-versus-host disease and its therapy on the antibody kinetics. In the group of allogeneic transplanted children without a GvHD the tetanus-antitoxin titers felt below their detection range after a time of about 8 months whereas in the group with GvHD this effect already occurred after nearly 4 months. The autologous transplanted patients have a positive antibody level til the time of 20 months after BMT. As a consequence of the lost protection by vaccination after BMT follows the necessity of revaccinations respectively of boostering after immunological reconstitution. PMID- 1495264 TI - [Fatal course of B-streptococcal infection in early infancy]. AB - We report on a fatal case of "late onset" -sepsis by B-streptococcus in a seven weeks olk suckling. B-Streptococcus is considered to be a typical strain of early stage neonatal sepsis that is connected with foudroyant progress and high letality. As in our case the outcome is decisively determined by early diagnosis and timely beginning therapy for the strain can still be controlled effectively. Misjodging early symptoms of the infection may lead to fateful progression even after the neonatal period. PMID- 1495265 TI - [Cold agglutinin syndrome after rubella infection]. AB - Cold agglutinins are antibodies against erytrocyte membrane antigens, and are produced primarily or secondarily. We report on the case of a 5 year old girl who developed cold agglutinin disease 3 days after an attack of German measles. Following exposure to cold, appeared blue-red cutaneous manifestations of the fingers, hands cheeks and nose. The clinical manifestations cleared up without any specific therapy. The occurrence of cold agglutinins after German measles is rare. The case report is discussed within the context of reports in the literature. PMID- 1495267 TI - [Physician and public health physician rights briefly examined. I: Medical society--public health commission]. PMID- 1495266 TI - [Effect of air pollutants on the health of the Annaberg district population with special reference to acute respiratory tract diseases]. AB - From 1978 to 1988 in the district of Annaberg (Saxony, state frontier to Czechoslovakia) investigations were accomplished to assess the state of health in people living there. The southern part of the district rises to a crest (Saxon Ore Mountain). It is influenced by air pollution from Northern Bohemia. The incidence of acute infections of the upper airways showed a remarkable dependence on the degree of air pollution in the age groups up to 18 years, especially in the group of infants. In the polluted area (high overload) the morbidity of infants was 7-fold in relation to the unpolluted area of the district. In the polluted area when temperature was lower than -5 degrees C the incidence of acute respiratory infections in infants closely correlated (r = 0.90) with the concentration of SO2 in ambient air. In the town Annaberg (urban air pollution) the frequency of absence of children from school caused by acute respiratory infections was elvated in relation to the rural parts of the district, but there were no differences among these rural parts. In the polluted area the severe stages of cardiorespiratory diseases were passed through with evident acceleration. In healthy adults living there the mean values for immunoglobulins of class A and class M tended to be elevated, and in school children the antibody titers against influenza A and B were increased. PMID- 1495268 TI - Epidemiological and clinical study of autistic children in Yogyakarta, Indonesia. AB - This epidemiological study of autistic children was carried out in Yogyakarta, Indonesia. The approaches considered included the analysis of cross-sectional data on non-verbal intelligence, social maturity behavior or adaptive skills test by using statistical or sampling controls. The 5,120 children studied were all Javanese. Doctors, nurses of Public Health Centers and school teachers assisted in assessing the above subjects. The Bryson's screening scale for evaluating autistic children was used. A total of 66 children who scored above 16 were identified. Final diagnosis was done by means of CARS. Six children, who lived within Yogyakarta Municipality, were identified. The prevalence rate of autism within the birth cohort who were born between June 1984 and May 1991 was 12 per 10,000. Observations of the social interactions of 6 autistic and 6 normal children of equivalent mental age were carried out during a free play situation and reunion situation with mother and a stranger. A comparison of the two groups during social interaction made it clear that the autistic children showed more attachment, directed more social-interaction and more physical contact toward their mothers than to strangers during the reunion situation. PMID- 1495269 TI - A comparison of the bone mineral density of the vertebral bodies and the hip in elderly females with hip fractures. Assessment using dual photon absorptiometry. AB - The influence of decreasing bone mineral density with age and the occurrence of hip fractures in elderly females was investigated. Normal hips were studied in 287 healthy women whose ages ranged from 20 to 90 years old. The normal hip in 61 patients who had all suffered a femoral neck or intertrochanteric hip fracture, and were over 60 years old, were also studied and compared. The bone mineral density (BMD) of the lumbar vertebrae and the hip was measured with dual beam photon absorptiometry, for all patients. There was no correlation between the bone mineral density of the lumbar vertebral bodies, and the bone mineral density of the proximal femur. The peak bone mass in e lumbar vertebrae was seen in the thirties, but the peak bone mass in the hip was seen in the twenties. Bone mineral density in the lumbar vertebrae and in the hip was decreased in the patients who had sustained a hip fracture when compared to the control patients. The bone mineral density in the proximal femur was significantly reduced in patients who had sustained a hip fracture, especially in the region of Ward's triangle. These findings suggested that decreased bone mass in the hip at Ward's triangle may be correlated with the occurrence of hip fractures. PMID- 1495270 TI - The stimulatory GDP/GTP exchange protein for ras p21-related small GTP-binding proteins. AB - We have purified a novel type of regulatory protein for smg p21s, designated as smg p21 GDP dissociation stimulator (GDS), to near homogeneity from bovine brain cytosol. Moreover, we have isolated the cDNA of this protein from a bovine brain cDNA library, determined the complete nucleotide and deduced amino acid sequences, and characterized the kinetic properties. The cDNA of smg p21 GDS has an open reading frame encoding a protein of 558 amino acids with a calculated M(r) value of 61,066, similar to the M(r) value of 53,000 estimated for the purified smg p21 GDS by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and sucrose density gradient ultracentrifugation. smg p21 GDS stimulates the dissociation of [3H]GDP from and also stimulates the binding of [35S]guanosine 5' (3-O-thio)triphosphate (GTP gamma S) to smg p21s. These actions of smg p21 GDS were specific for smg p21s and inactive for other ras p21/ras p21-related small G proteins including c-Ha-ras p21 and smg p25A. Neither smg p21 GDS stimulate the GTPase activity of smg p21s nor by itself showed [35S]GTP gamma S-binding or GTPase activity. These results indicate that bovine brain contains regulatory proteins for smg p21s that stimulate the GDP/GTP exchange reaction of smg p21s in addition to smg p21 GAP. It is likely that the conversion from the GDP-bound inactive form of smg p21s to the GTP-bound active form is regulated by smg p21 GDS and that its reverse reaction is regulated by smg p21 GAP. PMID- 1495271 TI - An analysis of vitreous tamponade effect in encircling surgery by means of finite element method. AB - The vitreous tamponade effect in encircling surgery was investigated by means of a finite element method. We performed the simulated encircling surgery on a computer program, which could have alternative band positions, i.e. anterior or posterior band position. Computed results revealed that the band position has a great influence on the vitreous stress distribution, and that the anterior band position is more advantageous than the posterior band position with regard to the vitreous tamponade effect. To our knowledge, this is the first numerical experiment to demonstrate the advantage of the anterior band position in encircling surgery. PMID- 1495272 TI - Effect and limitation of intra-aortic balloon pumping following valve replacement surgery. AB - To evaluate the effect and the limitation of intra-aortic balloon pumping (IABP) in patients with severe left ventricular failure (LVF) following valve replacement surgery, we assessed the results of 282 patients who underwent such surgery. Among 25 patients in whom IABP was used after valve replacement, 17 patients could be weaned from IABP, and 14 of them achieved long-term survival. The durations of IABP support for patients who were weaned from IABP were shortened and were mostly within 48 hours, whereas those in patients not weaned from IABP tended to be prolonged. Among 25 IABP patients, 8 had definite causes of LVF such as perioperative myocardial infarction, but the other 17 patients experienced LVF despite uneventful operation. In the latter group of patients, preoperatively depressed left ventricular function was observed in 10 patients. In the former group of patients, the duration of IABP was much longer, and the weaning rate, as well as survival rate, was significantly poorer. On the other hand, in the latter-group patients, the duration of IABP was shortened and the survival rate was excellent. In conclusion, IABP support for patients with postoperative LVF of unknown causes, which might include patients with preoperatively depressed left ventricular function, was sufficiently effective, whereas no significant effect of IABP was noted for patients experiencing LVF after definite and serious perioperative complications. PMID- 1495273 TI - [Environment and nursing (II). Management of the hospital environment]. PMID- 1495274 TI - [Nursing management for the hazards of immobility--cardiovascular system, respiratory system, metabolism and nutrition]. PMID- 1495275 TI - [Nursing management for the hazards of immobility--musculoskeletal system, bowel and urinary elimination]. PMID- 1495276 TI - [Effects of immobility: psychosocial aspects & its management]. PMID- 1495277 TI - [Make room for laughter]. PMID- 1495278 TI - [Nursing study on rehabilitation of spinal cord injury client at home]. PMID- 1495279 TI - [A study of the effectiveness of the bereavement program of Severance Hospice]. AB - Grief that is not acknowledged and worked through may manifest itself in some emotional, mental or physical problem. In recent years much as been learned about coping with grief which the hospice program can utilize to help family members cope with their grief. This study was carried out to determine the helpfulness of the bereavement care of Severance Hospice and to learn more about the grief response of the bereaved. The tools used to collect data were an assessment form used in the bereavement program and the Grief Experience Inventory developed by Sanders and revised and translated by the researcher. Data was obtained from bereaved family members (54 for the final grief assessment and 39 for the grief response assessment) receiving bereavement follow-up, from July 1989 to March 1991. Results of the study were as follows: 1. Final Grief Assessment Regarding the resolution of their grief the majority of the bereaved accepted the reality of the death of their family member, while slightly more than three-quarters were able to express their feelings toward their loss. A large majority had returned to activities of daily living well or fairly well and had reinvested their energy in a person other than the deceased. In addition, the physical condition of the majority was good or fairly good. A majority of the bereaved considered the bereavement care to be helpful and almost three-quarters were not considered to be in need of more follow-up. 2. Grief Response Assessment Age was found to have a moderately positive correlation to appetite disturbance (r = .41, P less than .01) and loss of vigor (r = .37, P less than .01) A moderately positive correlation was found between the number of contacts and sleep disturbance (r = 2.38, P less than .01) Significant differences were found between men and women in regard to guilt (t = 2.38, P less than .05), social isolation (t = 2.44, P less than .05) and depersonalization (t = 2.07, P less than .05) with men having the more intense grief. Significant differences were found in the grief responses of somatization (F = 5.82, P less than .001), physical symptoms (F = 5.87, P less than .001), appetite disturbance (F = 4.40, P less than .01), despair (3.79, P less than .01), anger (Fp2.83, P less than .05), social isolation (F = 3.61, P less than .05), guilt (F = 3.62, P less than .05) and depersonalization (F = 2.58, P less than .05).(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1495280 TI - [Environment and nursing (II). Management of school environment in Korea]. PMID- 1495282 TI - [Childbirth education]. PMID- 1495281 TI - [A study on Korean concepts of relaxation]. AB - Relaxation technique is an independent nursing intervention used in various stressful situations. The concept of relaxation must be explored for the meaning given by the people in their traditional thought and philosophy. Korean relaxation technique, wanting to become culturally acceptable and effective, is learning to recognize and develop Korean concepts, experiences, and musics of relaxation. This study was aimed at discovering Korean concepts, experiences and musics of relaxation and contributing the development of the relaxation technique for Korean people. The subjects were 59 nursing students, 39 hospitalized patients, 61 housewives, 21 rural residents and 16 researchers. Data were collected from September 4th to October 24th, 1991 by interviews or questionnaires. The data analysis was done by qualitative research method, and validity assured by conformation of the concept and category by 2 nursing scientists who had written a Master's thesis on the relaxation technique. The results of the study were summarized as follows; 1. The meaning of the relaxation concept; From 298 statements, 107 concepts were extracted and then 5 categories "Physical domain", "Psychological domain", "Complex domain", "Situation", and "environment" were organized. 'Don't have discomforts, 'don't have muscle tension', 'don't have energy (him in Korean)', 'don't have activities' subcategories were included in "Physical domain". 'Don't have anxiety', 'feel good', 'emotional stability', 'don't have wordly thoughts', 'feel one's brain muddled', 'loss of desire' subcategories were included in "physical domain" 'Comfort body and mind', 'don't have tension of body and mind', 'be sagged' 'liveliness of thoughts' subcategories were included in "Complex domain". 'Rest', 'sleep', 'others' subcategories were included in "Situation domain". And 'quite environment' & 'comfortable environment' subcategories were included in "Environmental domain". 2. The experiences of the relaxation; From 151 statements, 59 experiences were extracted. And then 9 categories--at rest after physical activities, after problem solving, fancy, bathing in the bed, situation, rest, particular time, others--were organized. 3. The musics of the relaxation; From 229 statements, 108 musics were extracted, and the 9 categories--Western classical music, semi classical music, Korean song, Korean popular classical music, song, western popular song, hymn, characteristics of music, others--were organized. In conclusion, There are some differences between Korean concepts, experiences and musics of relaxation and western concepts, experiences and musics of relaxation. PMID- 1495283 TI - Cardiac transplantation after prolonged graft preservation with the University of Wisconsin solution. AB - We tested the ability of University of Wisconsin solution to extend hypothermic preservation of the nonperfused heart during orthotopic baboon allotransplantation. Seven baboons received hearts after cardioplegia and storage (4 degrees C) with University of Wisconsin solution, with a preservation time of 14.2 +/- 1.6 hours. One animal died as a result of a technical error. Six survivors were immunosuppressed for 45 days and then put to death. Preservation did not alter heart weight or histologic features according to light and electron microscopy. Animals were weaned from bypass and returned to their cages without intravenous support within 3.9 +/- 0.8 hours. Weekly biopsies, electrocardiograms, enzyme analyses, echocardiograms, and right heart catheterizations demonstrated excellent cardiac function. University of Wisconsin solution can extend hypothermic cardiac preservation and has no deleterious effects on long-term myocardial function (up to 45 days). This study validates the rationale for human trials with preservation and storage in University of Wisconsin solution toward the goal of improving and prolonging donor heart preservation. PMID- 1495284 TI - Superior qualities of University of Wisconsin solution for ex vivo preservation of the pig heart. AB - The components of the University of Wisconsin solution have the potential to enhance and extend heart preservation. We have evaluated University of Wisconsin solution by comparing it with St. Thomas' Hospital cardioplegic solution in the isolated pig heart subjected to 8 hours of ischemia at 4 degrees C (n = 6 in each). The hearts were perfused ex vivo with enriched autologous blood for the control and the postpreservation assessments. Morphologic, metabolic, and functional evaluations were performed. Left and right ventricular function as assessed by the slope values of systolic and diastolic pressure-volume relationships of isovolumically contracting isolated heart was better preserved by University of Wisconsin solution (percent reduction: left ventricular systolic, 52.4% +/- 5.5% versus 17.7% +/- 6.7% [p less than 0.001]; right ventricular systolic, 125.6% +/- 46.4% versus 65.5% +/- 31.4% [p less than 0.05]; right ventricular diastolic, 112.3% +/- 48.7% versus 40.2% +/- 31.3% [p less than 0.02] after St. Thomas' Hospital and University of Wisconsin preservation, respectively). Postischemic recovery of left ventricular rate of rise of pressure and myocardial oxygen consumption were significantly improved after University of Wisconsin preservation (percent reduction, rate of rise of pressure: St. Thomas' Hospital 39.3% +/- 8.1%; University of Wisconsin 18.1% +/- 4.6%; percent reduction, myocardial oxygen consumption St. Thomas' Hospital 55.1% +/- 6.9%, University of Wisconsin 24.8% +/- 6.7%; p less than 0.001). Microvascular functional integrity as assessed by coronary vascular resistance was well maintained throughout the postischemic period and was similar to the preischemic control value in the University of Wisconsin group. By contrast, a significant increase was found at the beginning of postpreservation reperfusion, with a progressive rise thereafter in the St. Thomas' Hospital group (p less than 0.001). Preservation of myocardial adenosine triphosphate was improved and energy charge was unchanged after 8 hours of ischemia and reperfusion in the University of Wisconsin-preserved hearts compared with the St. Thomas' Hospital-preserved hearts (p less than 0.01). Electron microscopic examination revealed substantially better preservation of the contractile apparatus after preservation with University of Wisconsin solution. Myocytes from hearts receiving University of Wisconsin solution, unlike those given St. Thomas' Hospital solution, showed relaxed myofibrils with prominent I-bands. We conclude that University of Wisconsin solution has the potential to improve the preservation of the heart and possibly prolong the ischemic period in clinical cardiac transplantation. PMID- 1495285 TI - The determinants of elevated total plasma cholesterol levels in cardiac transplant recipients administered low dose cyclosporine for immunosuppression. AB - Elevated total plasma cholesterol level is a frequent finding after cardiac transplantation. To identify risk factors for the development of hypercholesterolemic states, we applied multivariate statistics in a logistic and linear manner. Six-month posttransplantation levels of total plasma cholesterol in 57 adult heart recipients were available for analysis. Maintenance immunosuppression was carried out with either cyclosporine and azathioprine or both agents plus low-dose steroids. Total plasma cholesterol levels were dichotomized for the logistic analysis (1) by the age- and sex-matched 75th and 90th percentiles of a reference population according to National Institutes of Health treatment guidelines and (2) by the cut point 250 mg/dl. Twelve potential risk factors were evaluated as covariates: recipient age, body weight after 6 months, body weight gain over 6 months, body mass index after 6 months, body mass index gain over 6 months, current cyclosporine dosage, trough level of cyclosporine in whole blood according to high-performance liquid chromatography after 6 months, cumulative cyclosporine dosage over 6 months, serum bilirubin, type of original cardiac disease, maintenance steroids, and steroid bolus treatment. Multivariate logistic regression yielded the type of original cardiac disease as a significant predictor of posttransplantation hypercholesterolemia exceeding the 90th percentile (p = 0.019) and of hypercholesterolemia exceeding 250 mg/dl (p = 0.032). Maintenance steroids were identified as a second significant cofactor (p = 0.069) for total plasma cholesterol levels exceeding 250 mg/dl. Multiple linear regression again revealed the type of original cardiac disease and maintenance steroids as significant predictors by p values of 0.005 and 0.013, respectively. Patients with coronary artery disease as the original cardiac pathology and low-dose maintenance steroids had the greatest risk for the development of elevated total plasma cholesterol levels after cardiac transplantation. However, the overall predictive quality of the linear model was limited (multiple r value 0.43), which indicates that other variables besides the tested ones attributed to elevated total plasma cholesterol levels. These results confirm the adverse role of maintenance steroids on posttransplantation hypercholesterolemia and demonstrate the type of original cardiac disease as the most important risk factor. They suggest that abnormalities of lipoprotein metabolism and dietary factors continue to affect total plasma cholesterol levels after cardiac transplantation. PMID- 1495286 TI - Hemodynamic evaluation of heterotopic heart transplantation. AB - To assess the relative contribution of native and donor hearts to total circulatory performance after heterotopic transplantation, we used cardiac catheterization to examine 10 patients. Left and right ventricular filling pressures significantly decreased by 41% and 36%, respectively, cardiac index increased by 25%, and pulmonary arteriolar resistance was reduced by 61%. Patients were subdivided into two groups according to the presence of one (group I) or two (group II) peaks on the aortic pressure curve. In group I, the donor left ventricle assumed total left ventricular work and 80% of right ventricular work. Because the native left ventricle could not generate enough pressure to open the aortic valve, its entire stroke volume was ejected into the common left atrium. In addition, in all four patients a native aortic regurgitation occurred in diastole and systole. In contrast, in group II, native left ventricular systolic pressure always exceeded aortic diastolic pressure. The donor left ventricle contributed 68% to systemic blood flow and the donor right ventricle 51% to pulmonary blood flow. Mild native aortic regurgitation was demonstrated in two patients only. Native left ventricular function deteriorated postoperatively in all patients (ejection fraction decreased from 0.22 +/- 0.09 to 0.14 +/- 0.08), but this deterioration was more marked in group I. Postoperative depression of native left ventricular function could not be ascribed to progression of coronary artery disease but was mainly due to reduced preload (competitive filling) and increased afterload. Thus in group I patients with more severe preoperative left ventricular dysfunction, the donor heart behaved like a total biventricular assist device. In contrast, in group II patients the donor heart acted like a partial biventricular assist device. PMID- 1495287 TI - Pharmacologic interventions for prevention of spinal cord injury caused by aortic crossclamping. AB - The efficacy of pharmacologic agents for prevention and control of oxygen-derived free radical damage in ischemia-reperfusion injury of the spinal cord was assessed in a swine model of thoracic and thoracoabdominal aortic crossclamping. Animals were exposed to 30 minutes of ischemia that induced lethal, irreversible injury and paraplegia. The experimental groups were as follows: group A (n = 7), control group, receiving no pharmacologic intervention; group B (n = 7), deferoxamine 50 mg/kg/day administered intravenously over 3 to 4 hours before ischemia; group C (n = 7), allopurinol pretreatment 50 mg/kg/day for 3 days; and group D (n = 7), superoxide dismutase 60,000 units administered with 50,000 units before removal of the aortic crossclamp and 10,000 units over 10 minutes of reperfusion. Proximal hypertension was controlled with sodium nitroprusside and volume depletion. The methods of assessment were neurologic by a modified Tarlov criteria and blood flow by radiolabeled microspheres. Results of blood flow assessment confirmed a true ischemic episode of 30 minutes for all animals in all groups. The blood flow fell significantly during ischemia (p less than 0.01) and a hyperemic response was evident in the early reperfusion period. All animals in control group A were paraplegic. The group B (deferoxamine) results were superior; 85% had grade III function on a modified Tarlov scale, with animals in the group standing and even walking with difficulty. Only one animal in this group had good movements of hind limbs but was unable to stand or walk. Neurologic recovery was limited in the allopurinol group (group C), with 85% showing slight neurologic recovery with limited movement of the hind limbs. The animals in the superoxide dismutase group (group D) all had good recovery, with strong motor response of hind limbs, but were not able to stand. In summary, the results of this experimental protocol confirmed the possible role of oxygen derived free radicals in the pathophysiology of spinal cord injury, induced by aortic crossclamping. Moreover, it proved that ischemia-reperfusion injury could be altered by pharmacologic interventions. PMID- 1495289 TI - Changes in plasma free thyroid hormones during cardiopulmonary bypass do not indicate triiodothyronine substitution. AB - Concentrations of free and bound thyroid hormone in plasma during cardiopulmonary bypass were determined in 10 patients. Ages ranged from 50 to 76 years (median 61 years). Apart from thyroxine and triiodothyronine, a number of other variables that might contribute to an altered thyroid state or binding of thyroxine and triiodothyronine to plasma proteins were measured (thyroid stimulating hormone, reverse triiodothyronine, albumin, nonesterified fatty acids, and cortisol). At the end of the observation, total triiodothyronine and total thyroxine concentrations were 86% and 70% (mean) of initial levels, respectively, and reverse triiodothyronine and albumin concentrations were both 74%. On the contrary, free triiodothyronine and free thyroxine levels rose to a maximum of 137% and 203% (mean), but normalized after heparin neutralization (86% and 102%). Thyroid-stimulating hormone concentration declined insignificantly during cardiopulmonary bypass, reaching a minimum at the time when body temperature was maximally depressed (74%), and then it normalized (101%). Plasma cortisol level did not rise above normal limits despite the major stress stimulus. In conclusion, total triiodothyronine and total T4 concentration in plasma of patients undergoing cardiac operations is lowered, while the exchangeable pool concentrations (plasma free triiodothyronine and free thyroxine) are elevated during bypass but return to control levels at the end of the operation. If serum changes truly reflect intracellular events, it does not seem likely that the myocardial cell is depleted of thyroid hormones after cardiopulmonary bypass, as recently claimed by others. This finding does not, however, exclude the possibility that a pharmacologic dose of triiodothyronine may be convenient for improvement of cardiac performance. PMID- 1495288 TI - Correlation of motor-evoked potential response to ischemic spinal cord damage. AB - The prevalence of morbidity is a major deterrent to the success of aortic aneurysm replacement operations. We have developed a model of spinal cord ischemia, based on the amplitude reduction of the motor-evoked potential, which produces approximately a 90% prevalence of paraplegia. Regional blood flow was studied with the use of radioactive microspheres, and results showed that there was a significant decrease in flow to the lumbar cord (85% reduction) during aortic occlusion, followed by a twofold to threefold hyperemia that persisted for 24 hours. Histopathologic examination of the cord revealed that the greater portion of microgliosis, spongiosis, and neuronal damage was confined to the gray matter of the cord, and its severity increased as one progressed caudally. The somatosensory-evoked potential disappeared before the motor-evoked potential L-2 signal in all dogs, with a mean disappearance time of 10.9 +/- 5.6 minutes, compared with 21 +/- 6.6 minutes for the motor-evoked potential. Both the sensory evoked potential and the motor-evoked potential cord signal were present 24 hours later in all dogs tested. The peripheral nerve motor-evoked potential disappeared within 1 minute of cord ischemia, was not present 24 hours later, and hence appears to be too sensitive to use as an indicator of spinal cord damage. Plotting spinal cord motor-evoked potential amplitude reduction versus both histopathologic damage and regional blood flow revealed a positive correlation between motor-evoked potential amplitude reduction, decreased cord perfusion, and increased histopathologic damage. In addition, it may be possible to make inferences about the neurologic status of a subject based on the magnitude and time-course of the motor-evoked potential's amplitude reduction and wave morphology. PMID- 1495290 TI - The effect of augmented atrial hypothermia on atrial refractory period, conduction, and atrial flutter/fibrillation in the canine heart. AB - The purpose of this study was to test the assumption that the cause for postoperative atrial flutter/fibrillation after cardiopulmonary bypass is inadequate atrial myocardial protection. Dogs were subjected to cardioplegic arrest for 60 minutes without augmented atrial hypothermia (seven dogs, control group) or augmented atrial hypothermia with topical atrial cooling (seven dogs, study group). Twenty-five electrodes (15 on the right atrium and 10 on the left atrium) were fixed on the atria to measure effective refractory period and conduction time. Data were taken before bypass, immediately after bypass, and 2 hours after bypass. During cardioplegic arrest the mean temperatures measured in the atria were significantly lower (p less than 0.001) in the study group (13.5 degrees +/- 7.0 degrees C) than in the control group (23.7 degrees +/- 3.2 degrees C). There was no significant change in the mean effective refractory period after bypass in the control or study groups or in the prevalence of inducibility of atrial flutter/fibrillation by extrastimulation (3/7 dogs in the control group and 2/7 in the study group). During right atrial pacing, total conduction times were significantly longer (p less than 0.025 at cycle lengths of 300 and 350 msec) in the control group (74 +/- 5 msec and 75 +/- 7 msec, respectively) than in the study group (65 +/- 9 msec and 64 +/- 8 msec, respectively) immediately after bypass. Two hours after bypass, however, there were no significant differences under the same conditions between the two groups. There were no significant differences in conduction during left atrial pacing after bypass. Comparing those atria that were inducible with those not inducible demonstrated a significantly increased dispersion of effective refractory period (90 +/- 23 msec versus 74 +/- 18 msec, p less than 0.05) and increased conduction time in the inducible group. We concluded that augmented atrial hypothermia during cardioplegic arrest had no effect on the inducibility of fibrillation, had no effect on repolarization, and had only a small effect on conduction, which resolved within 2 hours after bypass. However, the study demonstrates that when the atria are inducible the substrates are an increased dispersion of refractoriness and a prolongation of conduction time. PMID- 1495291 TI - Comparison of two transfusion strategies after elective operations for myocardial revascularization. AB - We performed a prospective, randomized trial of two different strategies for postoperative packed red blood cell replacement in 39 autologous blood donors undergoing elective myocardial revascularization. The "liberal" group received blood to achieve a hematocrit value of 32%, and the "conservative" group received transfusions for a hematocrit value less than 25%. Although the groups had significantly different mean hematocrit values from the fourth postoperative hour (28.7% versus 31.2%) through the fifth postoperative day (28.4% versus 31.3%), there were no significant differences in fluid requirement, hemodynamic parameters, or hospital complications. Significantly fewer units of packed cells were required in the conservatively transfused group (20 units/20 patients) compared with the liberally transfused group (37 units/18 patients) (p = 0.012). Exercise tests were performed on the fifth and sixth postoperative days, with a transfusion being given to the conservative group between tests. Although a significant improvement in exercise endurance occurred in the conservative group receiving a transfusion (p = 0.008), no significant difference in duration or degree of exercise was demonstrated between the two groups on either day. In comparing these two groups of profoundly anemic patients, we identified no adverse consequence associated with the greater degree of hemodilution and could identify no correlation between hematocrit value and exercise capacity. We conclude that although the limits of hemodilution are still poorly defined, postoperative blood transfusion in revascularized patients should be guided by clinical indications and not by specific hematocrit values. PMID- 1495292 TI - Continuous thermodilution cardiac output measurement in sheep. AB - A technique has been developed to continuously measure cardiac output by means of the principles of thermodilution. Pulmonary artery catheters were modified by placing a 10 cm filament near the usual injectate port. Small amounts of heat were infused according to a randomly repeating binary on-off sequence. The distal blood temperature was recorded and cross-correlated with the heat waveform to produce a dilution curve and calculate cardiac output. The technique was compared with bolus thermodilution in seven sheep. Cardiac output ranged from 1.5 to 13.2 L/min, and heart rate varied from 59 to 180 beats/min. The linear regression between the data obtained by the two methods is represented by the equation y = 1.00x + 0.13; the correlation coefficient, R, is 0.97, and the p value is less than 0.0001. PMID- 1495293 TI - Transesophageal echocardiography in hypotensive patients after cardiac operations. Comparison with hemodynamic parameters. AB - Because it is sometimes difficult to determine the cause of hypotension in patients after cardiac operations, we assessed the value of transesophageal echocardiography in this respect, and we studied 60 consecutive patients who had hypotension despite positive inotropic medication and, in some patients, mechanical support. Echocardiographic diagnoses were compared with diagnoses based on hemodynamic parameters. Follow-up examinations were completed in all patients to confirm the final diagnoses. Echocardiographic signs of hypovolemia were present in 14 patients, tamponade in six, left ventricular failure in 16, right ventricular failure in 11, and biventricular failure in eight. Echocardiographic examination proved to be inconclusive in five patients. Comparison with hemodynamic parameters showed agreement on diagnoses (hypovolemia versus tamponade versus cardiac failure) in 30 patients (50%). Echocardiography correctly identified two patients with tamponade and six with hypovolemia; these conditions were not suspected by standard hemodynamic data; in five patients unnecessary reoperation was prevented, although hemodynamic values were suggestive of tamponade. Echocardiography also identified subcategories of patients at high risk of death (those with signs of right ventricular and biventricular failure). These findings suggest that transesophageal echocardiography performed on patients after cardiac operations, at the bedside in the intensive care unit, can readily elucidate the cause of hypotension in the large majority of patients and is a valuable adjunct to hemodynamic evaluation in patient management. Furthermore, it appears to be possible to identify subcategories of high-risk patients, based on these echocardiographic findings. PMID- 1495294 TI - The effect of calcium on pulmonary vascular resistance and right ventricular function. AB - Calcium chloride is frequently administered to patients immediately after separation from cardiopulmonary bypass to improve the contractile state of the myocardium. Animal studies suggest that calcium chloride may produce increases in pulmonary vascular resistance, which can precipitate right ventricular failure. In an attempt to determine the effect of calcium chloride administration after cardiopulmonary bypass on right ventricular function, this study was designed to evaluate patients with normal and elevated pulmonary vascular resistance. Fifty patients scheduled for elective cardiac surgery were prospectively studied for changes in ionized calcium levels before and after bypass. The impact of calcium administration on right ventricular function was assessed by a pulmonary artery catheter modified for the measurement of right ventricular ejection fraction. In all patients the level of ionized calcium decreased during bypass from a mean of 4.91 to 4.29 mg.dl-1. However, the infusion of calcium chloride (10 mg.kg-1) after bypass resulted in increasing the ionized calcium levels to prebypass levels. Administration of calcium chloride after bypass to patients with normal right ventricular function resulted in a transient increase in both cardiac output and right ventricular ejection fraction without any change in pulmonary vascular resistance. Eight patients with both elevated pulmonary vascular resistance and depressed right ventricular function were evaluated to determine the effect of calcium chloride after bypass on pulmonary vascular resistance and right ventricular ejection fraction. Administration of calcium chloride (10 mg.dl 1) to these patients did not result in any significant increase in pulmonary vascular resistance or depression of right ventricular performance. More important, in these patients, right ventricular ejection fraction and cardiac output were significantly increased after calcium chloride administration. In summary, the results of this study fail to demonstrate any increase in pulmonary vascular resistance or deterioration of right ventricular function with the administration of calcium chloride (10 mg.kg-1) after bypass in patients with elevated pulmonary vascular resistance. PMID- 1495296 TI - Transient hypocalcemic reperfusion does not improve postischemic recovery in the rat heart after preservation with St. Thomas' Hospital cardioplegic solution. AB - We used the isolated perfused working rat heart to investigate the effects of transient hypocalcemic reperfusion after cardioplegic arrest with the St. Thomas' Hospital cardioplegic solution and 25 minutes of global normothermic (37 degrees C) ischemia. Hearts were reperfused (Langendorff mode) transiently (20 minutes) with solutions containing various concentrations of calcium; this was followed by 30 minutes of reperfusion with standard (1.4 mmol/L, the physiologic concentration) calcium buffer (10 minutes in the Langendorff mode and 20 minutes in the working mode). Recovery of cardiac output in control hearts (calcium concentration 1.4 mmol/L throughout) was 51.7% +/- 4.6%; in hearts transiently reperfused with hypocalcemic buffer (0.25, 0.5, 0.75, or 1.0 mmol/L) the recoveries of cardiac output were 49.3% +/- 6.4%, 52.2% +/- 7.2%, 58.7% +/- 3.2%, and 47.2 +/- 4.7%, respectively (all not significant), whereas recovery was only 14.7% +/- 2.8% (p less than 0.05) in hearts transiently reperfused with calcium 0.1 mmol/L. Creatine kinase leakage was significantly (p less than 0.05) greater in the group reperfused with calcium 0.1 mmol/L, but it did not vary significantly between the other groups. Tissue high-energy phosphate content was similar and in the normal range in all groups except for the group reperfused with calcium 0.1 mmol/L. In further experiments, the duration of hypocalcemic (0.5 mmol/L) reperfusion was varied (0, 5, 10, 15, 20, or 30 minutes). No significant differences in recovery of cardiac output were observed (58.2% +/- 5.0%, 52.3% +/- 5.7%, 52.0% +/- 8.2%, 61.2% +/- 5.0%, 62.2% +/- 4.3%, and 66.2% +/- 3.2%, respectively). In additional studies, the standard calcium concentration (1.4 mmol/L) used before and after ischemia was replaced by hypercalcemic solution (2.5 mmol/L). Despite this, transient (10 minutes) hypocalcemic (0.5 mmol/L) reperfusion did not improve recovery. Finally, studies were undertaken with a longer duration of ischemia (40 minutes), and although recovery of cardiac output in the hypocalcemic group (0.5 mmol/L for 10 minutes) tended to be higher than in the control group (29.7% +/- 4.8% versus 18.5% +/- 4.9%, respectively), statistical significance was not achieved. We conclude that in these studies transient hypocalcemic reperfusion did not afford any additional protection over and above that afforded by cardioplegia alone. PMID- 1495295 TI - The effect of intramyocardial pH on functional recovery in neonatal hearts receiving St. Thomas' Hospital cardioplegic solution during global ischemia. AB - The experiments in the present study were designed to address two issues: Is it possible to manipulate intramyocardial pH in neonatal hearts with different buffers in cardioplegic solution and, if so, do differences in intramyocardial pH during ischemia influence functional recovery? Isolated working hearts from 7- to 10-day-old rabbits underwent 60 minutes of cardioplegic arrest at 37 degrees C with cardioplegic washouts at the onset of ischemia and at 30 minutes. Hearts were reperfused with oxygenated physiologic saline solution (pH = 7.4), returned to the working mode for 30 minutes, and hemodynamic measurements were obtained to compare with baseline values. Intramyocardial pH was held constant during the ischemic interval by infusing cardioplegic solution containing different buffers: histidine (pK 6.0 at 37 degrees C), bicarbonate (pK 6.4), or tromethamine (pK 8.1). The intramyocardial pH was measured continuously with a Khuri glass electrode system (Vascular Technology, Inc., North Chelmsford, Mass.). Cardioplegic solutions buffered to pH values of 6.0 (histidine), 7.4 (bicarbonate), and 8.0 (tromethamine) were associated with ischemic intramyocardial pH values of 6.3 +/- 0.03, 7.02 +/- 0.05, and 7.88 +/- 0.06, respectively. Functional recovery was best in the acidic (histidine) and worst in the basic (tromethamine) groups. Recoveries of developed pressure, the rate of rise of pressure over time, and aortic flow were significantly better for each parameter in the bicarbonate-treated compared with the tromethamine-treated hearts (p less than 0.005). Recovery in the histidine group, however, was superior to that in both the bicarbonate-treated and the tromethamine-treated hearts (p less than 0.005). Regression analysis demonstrated that a significant inverse relationship existed between functional recovery and intramyocardial pH, supporting the conclusions that intramyocardial pH is an important determinant of functional recovery in the neonatal heart and that acidic conditions during normothermic ischemia optimize preservation of myocardial function. PMID- 1495297 TI - Altered effects of vasopressin on the coronary circulation after ischemia. AB - Ischemia and reperfusion alter the reactivity of large coronary arteries, but the effect of ischemia and reperfusion on the coronary microcirculation has been less well defined. Elevated circulating levels of vasopressin are associated with cardiopulmonary bypass and numerous other clinical states in which vascular ischemia and reperfusion may occur. We examined the effects of ischemia with and without reperfusion on the responses to vasopressin of both large coronary arteries and coronary arterial microvessels. Studies were performed on vessels from control dogs (n = 8), dogs undergoing 1 hour of ischemia only (n = 8), and dogs undergoing 1 hour of ischemia followed with 1 hour of reperfusion (n = 9). Rings of proximal obtuse marginal coronary arteries distal to the site of circumflex coronary artery occlusion were studied in isolated organ chambers. Coronary microvessels (110 to 220 microns in diameter) were studied in a pressurized (20 mm Hg), no-flow state with a microvessel imaging apparatus and electronic dimension analyzer. Microvessels were preconstricted with the thromboxane A2 analog U46619. Responses of large vessel rings were studied in the nonpreconstricted state and after preconstriction with prostaglandin F2 alpha. Large vessel response to vasopressin was minimal and not altered by ischemia with or without reperfusion. In contrast, ischemia markedly affected the coronary microvascular response to vasopressin (10 to 1000 microU/ml). Control coronary microvessels constricted minimally to vasopressin (4% +/- 2% of the baseline diameter), while microvessels after either ischemia alone or ischemia followed by reperfusion constricted 22% +/- 5% and 21% +/- 3%, respectively (p less than 0.05 versus control for both). Hemoglobin, which inactivates the endothelium-derived relaxing factor, augmented microvascular constrictions to vasopressin in all groups to a similar extent. Relaxations to the endothelium-independent agent nitroglycerin were not altered by ischemia. Constrictions of the coronary microcirculation to vasopressin in conditions such as cardiopulmonary bypass or myocardial ischemia, in which circulating levels of vasopressin are increased, may predispose to persistent myocardial ischemia in the perioperative setting. PMID- 1495298 TI - Myocardial oxygen consumption of fibrillating ventricle in hypothermia. Successful account by new mechanical indexes--equivalent pressure-volume area and equivalent heart rate. AB - We studied the effects of cardiac hypothermia on myocardial oxygen consumption of a fibrillating ventricle and evaluated whether myocardial oxygen consumption of a fibrillating ventricle in hypothermia can be accounted for by new mechanical indexes: equivalent pressure-volume area and equivalent heart rate in the isolated cross-circulated canine heart preparation. Equivalent pressure-volume area is the area that is surrounded by a horizontal pressure-volume line at the pressure of a fibrillating ventricle and the end-systolic and end-diastolic pressure-volume relations in the beating state in the pressure-volume diagram. Equivalent pressure-volume area is an analog of the pressure-volume area of a beating heart and has been proposed to be a measure of the total mechanical energy of a fibrillating ventricle. Equivalent heart rate was calculated from myocardial oxygen consumption per minute in both beating and fibrillating states under unloaded conditions as an estimate of the frequency of contractions of individual myocytes on the assumption that individual myocytes during ventricular fibrillation have the same contractility as that in the beating state. We estimated myocardial oxygen consumption per minute of the fibrillating ventricle at various ventricular volumes as a function of both equivalent pressure-volume area and equivalent heart rate. The myocardial oxygen consumption-equivalent pressure-volume area relation during ventricular fibrillation in hypothermia was highly linear, with a correlation coefficient of 0.90 (mean). The relation between estimated and directly measured myocardial oxygen consumption values of a fibrillating ventricle in hypothermia was highly linear (r = 0.98), and the regression line (y = 0.80x + 0.48) was close to the identity line in the working range. Therefore we conclude that equivalent pressure-volume area is the primary determinant of myocardial oxygen consumption during ventricular fibrillation in hypothermia, and myocardial oxygen consumption of a fibrillating ventricle in hypothermia can be accounted for by the combination of equivalent pressure-volume area and equivalent heart rate as in normothermia. PMID- 1495299 TI - Congenital respiratory-esophageal fistula in the adult. Report of nine cases and review of the literature. AB - Congenital tracheoesophageal or bronchoesophageal fistulas, if not associated with esophageal atresia, may not appear initially until adult life. Nine such cases (two tracheoesophageal and seven bronchoesophageal) are reported. The chief presenting symptoms were recurrent bouts of coughing, after drinking, and hemoptysis. In the majority of cases the duration of symptoms exceeded 15 years. The diagnosis was confirmed in seven patients by esophagography, in one patient by bronchoscopy, and in one patient the fistula was discovered incidentally during thoracotomy. The esophageal opening of the fistula was in the lower third in seven patients and in the middle third in two. Bronchoesophageal fistulas communicated with a segmental bronchus in four patients and with a main or lobar bronchus in three. Treatment involved excision of the fistula (five patients) or division and suturing (four patients). Postoperative follow-up revealed no long term sequelae except persistent chronic respiratory failure in one patient. The respiratory failure had developed before treatment of the fistula. The analysis of this series and a review of the literature underline the high index of suspicion required in all cases of chronic cough and lung suppuration, to diagnose this benign condition before life-threatening complications occur. PMID- 1495300 TI - Usefulness of perioperative pulsed Doppler flowmetry in predicting postoperative local ischemic complications after ileocolic esophagoplasty. AB - Regional ischemia may induce cervical anastomosis leakage or stenosis or graft necrosis after esophageal reconstruction by retrosternal interposition of an ileocolic graft. These complications may be related to systemic or local hemodynamic alterations. This study was designed to evaluate the relationship between immediate postoperative arterial blood supply to the graft, arterial patency monitored by angiography, and clinical outcome. Eight patients (mean age 30 +/- 4 years; standard deviation) were studied. Miniaturized Doppler implantable microprobes were sutured to the single artery supplying the graft and connected to an 8 MHz pulsed Doppler flowmeter. Systemic hemodynamic parameters and mesenteric hemodynamic data were collected 3 hours after the end of the surgical procedure. These data were compared with the angiogram of the right superior colic artery supplying the graft, systematically performed on the fifteenth postoperative day, and with the clinical course of follow-up for 3 months. Five patients (group 1) had excellent clinical and angiographic results. Mean mesenteric blood flow in these patients was 51 +/- 49 ml.min-1 (+/- standard deviation, ranging from 9 to 122). Three patients (group 2) had a poor clinical outcome. One had early complete graft necrosis and the two others had leakage of the cervical anastomosis with poor distal arterial vascularization of the graft on the angiogram. Mean mesenteric blood flow was nul in the first patient and, respectively, 24 and 28 ml.min-1 in the two others. Cardiac output and mean arterial pressure were in the same range for all patients. Phasic velocity shape analysis revealed that the three group 2 patients had an end-systolic or end diastolic reverse flow pattern that was not observed in the five group 1 patients, which suggested a submaximal increase in downstream vascular resistance. This reverse flow pattern seems to be a good predictor of ischemia related complications. We conclude that perioperative pulsed Doppler blood flow monitoring in an ileocolic graft may be useful for the diagnosis and prevention of ischemic complications. PMID- 1495301 TI - Quality of life three years or more after esophagectomy for cancer. AB - The quality of life and alimentary comfort of 17 patients with esophageal cancer who were disease free more than 3 years after an esophageal resection were evaluated by analyzing responses to a follow-up questionnaire. Fourteen patients had subtotal esophagectomy and gastric pull-up to the neck. Three patients underwent a total esophagopharyngolaryngectomy, the digestive continuity being restored by means of an isoperistaltic colon segment interposed between the base of the tongue and the stomach. Current body weight, when compared with that existing postoperatively, was increased in 13 patients and unchanged in four. The number of meals per day was an average of 2.8, but 12 patients took additional snacks between main meals (2.3 as a mean). The major long-term complaints were a sensation of early fullness during eating in 11 patients, dysphagia in three, diarrhea in two, cough-induced vomiting in two, and postprandial sweating in two. Ratings given by self-evaluation of current alimentary comfort in comparison with that predating the initial esophageal symptoms ranged from 3 of 10 to 10 of 10 (mean 7.1/10). Thirteen patients led active lives, seven at home and six employed outside the home. The present survey suggests that most disease-free patients may obtain a satisfactory quality of life after esophagectomy and gastric or colonic pull-up; long-term alimentary comfort is conditioned mainly by the small capacity of the esophageal substitute. PMID- 1495302 TI - Anastomotic complications after esophagectomy for cancer. A comparison of neck and chest anastomoses. AB - Leakage, tumor recurrence, and stricture formation at the anastomosis are serious problems after esophagectomy for cancer of the esophagus or cardia. Because the prevalence of these postoperative complications may be affected by whether an anastomosis is made in the neck or in the chest, a comparison was made between anastomoses made at these two sites. During a period of some 7 years, we studied prospectively 411 patients who underwent resection for cancer of the esophagus or cardia and, after immediate reconstruction, had an anastomosis made in the neck or chest. The anastomotic leak rate for the neck anastomosis group was 4.3% and for the chest anastomosis group, 3.7% (p = not significant). The difference between leak rates of anastomoses fashioned by hand-sewn (5.0%) or stapled (3.0%) techniques was also not significant. The median upper resection margins in the neck and chest anastomosis groups were 4.5 cm and 3.5 cm, respectively. The corresponding rates of anastomotic tumor recurrence were 6.1% and 8.1% (p = not significant). The prevalence of benign stricture formation was significantly higher in the chest anastomosis group (19.2%) than in the neck anastomosis group (9.0%) (p = 0.002). This difference was a reflection of a significantly increased prevalence of stricture formation when an anastomosis was made by the stapler technique than with the hand-sewn method, and whereas most of the anastomoses in the neck were hand sewn (90%) the majority of those in the chest were stapled (80%). There were thus no statistically significant differences between the sites in terms of anastomotic leak and tumor recurrence rates, and the higher stricture rate in the chest anastomosis group was the result of more stapled anastomoses. PMID- 1495303 TI - Results of surgical treatment for roentgenographically occult bronchogenic squamous cell carcinoma. AB - Ninety-four patients with roentgenographically occult bronchogenic squamous cell carcinoma had surgical resection. Fifty-three reported having no symptoms. In 83 carcinoma was detected by cytologic examination of the sputum during lung cancer screening. The carcinomas were located in segmental bronchi (34 cases), subsegmental bronchi (19 cases), divisional bronchi (17 cases), and subsubsegmental or more peripheral bronchi (15 cases). The number of cases classified by TNM staging were 16 Tis N0 M0, 72 T1 N0 M0, 4 T1 N1 M0, and 2 T2 N1 M0. Extrabronchial invasion of the resected carcinoma was observed in 17 lesions (16 cases). Five of six patients with lymph node metastasis in the resected specimens had carcinoma with extrabronchial invasion. Multiple primary lung cancers were observed in nine patients at the time of operation and in seven subsequently. Four of seven patients with subsequent primary lung cancer had surgical resection, and no recurrence was observed after the second operation. There were two deaths from lung cancer: One was caused by subsequent primary lung cancer and the other by mediastinal lymph node metastasis. In the 75 patients with intrabronchial cancer invasion and without lymph node metastasis who had complete resection, there was no local recurrence or metastasis of cancer. The 5 year survivals were 80.4% (death from all causes) and 93.5% (death from lung cancer). Although subsequent primary lung cancer is troublesome, operation is a reliable treatment for occult bronchogenic squamous cell carcinoma. PMID- 1495305 TI - Tumor emboli from lung neoplasms involving the pulmonary vein. AB - Systemic tumor embolization during pulmonary resection for lung neoplasms is an uncommon but potentially catastrophic complication. In recent months, two patients undergoing pulmonary resection for bronchogenic carcinoma were found at operation to have tumor extending into a pulmonary vein. Both patients had systemic tumor embolization, one with a fatal outcome because of occlusion of the superior mesenteric artery. The possibility of systemic tumor embolization should be considered in patients with large, central tumors and particularly those that abut the pulmonary veins. The implications of such pulmonary vein involvement is reviewed, and an algorithm for postoperative evaluation and management of these patients is presented. PMID- 1495304 TI - Accuracy of computed tomographic scan and surgical assessment for staging of bronchial carcinoma. A prospective study. AB - There is an increasing demand for accurate preoperative and intraoperative staging of bronchial carcinoma with respect to neoadjuvant therapy protocols and parenchyma-sparing operations. This study prospectively evaluated accuracy of computed tomographic scan and surgical assessment for staging of bronchial carcinoma in 108 consecutive patients. The stage of the primary tumor (T stage) was correctly determined in 85% of the patients, and surgical evaluation correctly determined the T stage in 92%. Invasion of major mediastinal structures posed a major problem for computed tomographic scan. On a node-by-node basis, computed tomographic scan predicted involvement of lymph nodes in 81% (sensitivity 29%, specificity 93%, positive predictive value 49%, negative predictive value 85%). The surgeon correctly determined the lymph node status in 69% of lymph nodes (sensitivity 90%, specificity 63%, positive predictive value 39%, negative predictive value 96%). On a patient-by-patient basis, computed tomographic scan correctly predicted the nodal status in 58% of patients. Accuracy of computed tomographic scan and surgical assessment in determination of the lymph node status strongly depended on tumor type and lymph node region (hilar or mediastinal region) studied. This was partly due to the fact that adenocarcinomas exhibited a high proportion of tumor-positive normal-sized lymph nodes, whereas squamous cell carcinomas showed a high proportion of enlarged tumor-free lymph nodes. In conclusion, computed tomographic scan and surgical assessment are sufficiently accurate for determination of the tumor stage but are insufficient in determining the nodal status. PMID- 1495306 TI - Growth of the hypoplastic aortic arch after simple coarctation resection and end to-end anastomosis. AB - Surgical treatment of a hypoplastic aortic arch associated with an aortic coarctation is controversial. The controversy concerns the claimed need to surgically enlarge the diameter of the hypoplastic arch, in addition to resection and end-to-end anastomosis. The purpose of this prospective study is to determine the fate of the hypoplastic aortic arch after resection of the aortic coarctation and end-to-end anastomosis. Between July 1, 1988, and January 1, 1990, 15 consecutive infants less than 3 months of age with an aortic coarctation were evaluated echocardiographically. A Z-value was calculated, being the number of standard deviations the aortic arch differs from the expected value, derived from a control group. Eight of these 15 infants had a hypoplastic aortic arch with a mean Z-value of -7.14 +/- 1.39. The other seven infants had a "normal" aortic arch with a mean Z-value of -1.85 +/- 1.08. All 15 infants underwent simple coarctation resection and end-to-end anastomosis. Six months after operation the mean Z-value increased significantly in those with a hypoplastic arch to -1.08 +/ 0.69 (p less than 0.0001) and in those with a "normal" aortic arch to 0.106 +/- 0.99 (p = 0.004). No infant died in our series (0%; CL 0% to 12%) and a recoarctation developed once (12.5%; CL 2% to 36%). Therefore we believe that simple resection and end-to-end anastomosis is the operation of choice for aortic coarctation associated with a hypoplastic aortic arch despite the presence of a ventricular septal defect and that enlargement of the hypoplastic aortic arch is not necessary. PMID- 1495307 TI - Morphology of the ventriculoaortic junction in critical aortic stenosis. Implications for hemodynamic function and clinical management. AB - The clinical presentation of infants with critical aortic stenosis, as well as the results of surgical treatment, differs from obstruction of the left ventricular outflow tract in older children. To investigate a possible anatomic basis for this situation, we performed a detailed morphometric study of 21 hearts from infants who had critical aortic stenosis and 11 normal hearts from infants less than 3 months of age. In each of the hearts with critical aortic stenosis, only one commissure extended to the sinutubular ridge. The other two commissures were represented by folds in the aortic wall that suspended the leaflet below the level of the sinutubular junction. The leaflet thus had a free edge shorter than the circumference of the sinus, in contrast with the normal valve, in which leaflets always were longer than the circumference of their supporting sinus. Analysis of the fibrous triangles on the ventricular aspect of abnormal valves showed a symmetric three-sinus arrangement. In all but one specimen, however, only the triangle related to the mitral valve was fully developed. Although incision of both rudimentary commissures to the aortic wall should achieve some relief of obstruction, these morphologic features strongly mitigate against surgical restoration of normal function or growth in aortic valves having the morphology observed in this series of hearts. PMID- 1495308 TI - Complete repair of total anomalous pulmonary venous connection in infancy. AB - From 1983 to 1990, 20 infants underwent complete repair of isolated total anomalous pulmonary venous connection. Twelve were male; ages ranged from 1 day to 240 days (mean 32 days). The abnormal anatomic connection was supracardiac in nine, cardiac in four, mixed in five, and infradiaphragmatic in two. In seven patients the pulmonary venous drainage was obstructed. Corrective operations were performed 2.4 days after admission; after medical stabilization, seven patients underwent emergency operations, including extracorporeal membrane oxygenation in one. All operations were performed with the use of circulatory arrest (mean 33 minutes) and cardiopulmonary bypass (mean 54 minutes). There was one hospital death, which occurred in a premature infant (1.5 kg) who had supracardiac drainage. No preoperative risk factors correlated with a poor surgical outcome. Pulmonary hypertensive episodes were expectantly managed after the operation with 100% oxygen, sedation, and hyperventilation. Postoperative arrhythmias occurred predominantly in patients with intracardiac drainage. All survivors (mean follow up of 42 months) are in sinus rhythm, receiving no medications, and are growing and developing normally. Surgical correction of total anomalous pulmonary venous connection in infancy can be performed at low risk with good results after aggressive preoperative stabilization and postoperative management. PMID- 1495309 TI - Left main coronary trunk compression by dilated main pulmonary artery in atrial septal defect. Report of three cases. AB - Narrowing of the left main coronary trunk, which was compressed by the dilated pulmonary artery, was associated with atrial septal defect in three adults. One of them had severe pulmonary hypertension. Coronary angiograms revealed localized narrowing of the left main coronary trunk, and the left main coronary trunk had a concave shape. No stenosis of other coronary arteries was observed. In all patients the atrial septal defect was closed with a polytetrafluoroethylene patch. In the patient with 75% narrowing of the left main coronary trunk, aorta coronary bypass was performed; it was not performed in the two with 50% narrowing. In two survivors postoperative coronary angiograms showed that the narrowing of the left main coronary trunk improved or disappeared. These results suggest that markedly dilated pulmonary arteries easily compress the left main coronary trunk and cause narrowing, which improves after atrial septal defect closure. PMID- 1495310 TI - Responses of human gastroepiploic arteries to vasoactive substances: comparison with responses of internal mammary arteries and saphenous veins. AB - We examined the responses of human gastroepiploic arteries to histamine, serotonin, and norepinephrine, comparing those of internal mammary arteries and saphenous veins. Fresh specimens of the vessels were obtained intraoperatively from 21 patients. The vessels were suspended in organ chambers to record isometric tensions. With gastroepiploic arteries, histamine induced relaxations in the endothelial rings (85% +/- 7%) but failed to induce any contractions or relaxations in the rings without endothelium. The relaxations were prevented by methylene blue or hemoglobin and the H1-histaminergic receptor antagonist chlorpheniramine. With internal mammary artery rings with endothelium, histamine at a low concentration (10(-8) to 10(-5.5) mol/L) induced relaxations (53% +/- 12%) but evoked contractions at a higher concentration (10(-5) to 10(-4.5) mol/L). With saphenous veins, histamine caused only contractions. Serotonin induced markedly greater contractions in saphenous veins than in either artery. The endothelium inhibited the maximal contraction in response to serotonin in both arteries but not in veins. With the gastroepiploic artery, the responses to norepinephrine and serotonin were similar to those of the internal mammary artery. Histamine induces endothelium-dependent relaxations only, and histaminergic receptors that induce contractions may be absent on vascular smooth muscle cells. These vasoactive properties may contribute to the high patency as a coronary graft. PMID- 1495311 TI - Similar endothelium-dependent relaxation, but enhanced contractility, of the right gastroepiploic artery as compared with the internal mammary artery. AB - The right gastroepiploic artery is an alternative coronary bypass graft. The excellent graft function of the internal mammary artery has been related to its physiologic properties, particularly to endothelial function. Isolated artery rings were suspended in organ chambers for recording of isometric tension. Norepinephrine and potassium chloride evoked threefold greater contractions in the gastroepiploic artery than in the mammary artery (p less than 0.01 to 0.05), whereas the sensitivity to the catecholamine was comparable. Acetylcholine induced endothelium-dependent relaxations, but the sensitivity (pD2: 6.7 +/- 0.3) and maximal relaxation (81% +/- 9%) were slightly less in the gastroepiploic artery than in the mammary artery (pD2: 7.6 +/- 0.2; 100% +/- 0%; p less than 0.05). Histamine induced endothelium-dependent relaxations with a similar sensitivity (pD2: 7.5 +/- 0.3 and 7.2 +/- 0.1), whereas the maximal relaxation was slightly enhanced in the gastroepiploic artery. The relaxation to the nitric oxide donor SIN-1 was identical in the two arteries. Thus the right gastroepiploic artery exhibits better contractility than the internal mammary artery but comparable endothelium-dependent and endothelium-independent relaxations. The good endothelial function of the gastroepiploic artery might be important for graft function and patency, whereas the enhanced contractility may facilitate vasospasm, especially in the presence of high circulating levels of catecholamines. PMID- 1495312 TI - Overcoming perioperative spasm of the internal mammary artery: which is the best vasodilator? AB - After mobilization, vasospasm often reduces flow through the internal mammary artery. An established method of relaxing the artery and increasing flow is to wrap it in a papaverine-soaked swab. To our knowledge the ability of other topical vasodilators to overcome spasm of the internal mammary artery has not been studied clinically. In 50 patients in whom the left mammary artery was used for myocardial revascularization, we have investigated the effect of five agents on internal mammary artery free flow. The agents investigated were normal saline, papaverine, nifedipine, glyceryl trinitrate, and sodium nitroprusside. Under controlled hemodynamic conditions, free flow was measured before any pharmacologic intervention and a median of 18.5 minutes after the pedicle had been sprayed with one of the five agents. Normal saline produced a small increase in flow from a median of 23 ml/min (range 17 to 88) to 38 ml/min (20 to 84) (not significant), whereas a significant increase occurred with papaverine, from 25 (16 to 78) to 43 ml/min (34 to 112) (p less than 0.01). Nifedipine and glyceryl trinitrate raised free flow by almost threefold, from 23 (14 to 66) to 71 ml/min (45 to 118) and from 23 (14 to 58) to 62 ml/min (46 to 126), respectively (both p less than 0.001). Sodium nitroprusside, however, with an increase in flow from 26 (10 to 58) to 108 ml/min (46 to 196), 250% over control, proved to be more effective than nifedipine and glyceryl trinitrate (p less than 0.05). We therefore recommend the topical use of sodium nitroprusside to relieve perioperative spasm of the internal mammary artery. PMID- 1495313 TI - Clamping of the atherosclerotic ascending aorta during coronary artery bypass operations. Its cost in strokes. AB - In 632 consecutive primary operations for coronary bypass grafting, the effect of instrumentation of the ascending aorta on the prevalence of stroke was evaluated. There were five surgical pathology groups: group A: soft aorta with no palpable disease, 463 patients; group B: distinctly palpable aorta with focal atheromas necessitating minor surgical modifications, 132 patients; group C, unclampable aorta (no plane for crossclamping the aorta without compression of atheromas was present), 16 patients; group D, untouchable aorta, in which the entire ascending aortic wall was involved by atheromatosis (these aortas were not touched), 14 patients; group E, aneurysmal aorta with soft walls, 7 patients. There were four strokes (0.63%), all related to instrumentations of the aorta. There were no cerebrovascular accidents in patients in whom precautions were taken. Of all risk factors studied, age was the only predictive one for major atheromatosis of the aorta (chi 2 test, p less than 0.001). Of the 30 patients in groups C and D, only one was younger than 60 years. PMID- 1495314 TI - Carcinoid disease of the heart. Surgical management of ten patients. AB - Between 1982 and 1989, 10 patients with carcinoid heart disease underwent tricuspid valve replacement with a mechanical prosthesis at our institution. Pulmonary valvectomy was performed in nine patients and pulmonary valve replacement with a pulmonary homograft was performed in one. Two patients had carcinoid tumor metastatic to the heart, involving the right atrium in one case and both ventricles in the other. One patient had concomitant coronary artery bypass with the saphenous vein, and one patient had a quadruple valve replacement for histologically proved carcinoid disease of all four valves. The 30-day mortality was 10% and the late mortality was 30%. The remaining six patients were alive 4, 4, 4, 7, 24, and 46 months postoperatively. A review of the English literature identified 28 additional patients who underwent tricuspid valve replacement for carcinoid heart disease. There was no significant difference in the survival of patients with a bioprosthesis versus a mechanical valve in the tricuspid position. The 4-year survival for the 38 patients undergoing tricuspid valve replacement for carcinoid heart disease was 48% +/- 13%. Symptomatic patients who have carcinoid heart disease and whose metastatic malignant disease is not an imminent threat to life should be offered valve replacement. Operating soon after the onset of increasing cardiac symptoms, before the often rapid deterioration in right ventricular failure, optimizes the benefits. PMID- 1495315 TI - Cardiac operations during active endocarditis. AB - Between December 1982 and March 1990, 65 patients with active infective endocarditis underwent cardiac operations. Their mean age was 28.6 years (range 1 to 65 years). The most common infecting organisms were staphylococcus (33.8%), streptococcus (18.5%), and brucella (16.9%); 11 patients (16.9%) had cultures negative for infection. A rheumatic, native valve, most commonly the aortic, was involved in 40 patients, a prosthetic valve (with the mitral most common) in 18 patients, and in seven patients the infection involved a congenitally abnormal valve. Aortic root abscess developed in 21.5% of patients. In 30 patients operation was performed within 3 days of the start of intravenous antibiotic therapy, usually within 3 days of admission (group A); this resulted in fewer preoperative complications and a significantly lower postoperative complication rate than in those 35 patients who underwent operations more than 3 days after starting antibiotic therapy (group B). Preoperative embolic phenomena occurred in eight (12.3%) of the 31 patients who had large, mobile vegetations (2/16 [12.5%] in group A and 6/15 [40%] in group B). Overall there was no reinfection. No postoperative paravalvular leaks developed in group A. Nine patients died in the hospital (13.8%) (four in group A and five in group B); in all patients the infecting organism was staphylococcal or fungal. There was one late death. Early operation should always be considered in active infective endocarditis, especially when a prosthetic valve is involved or the infecting organism is staphylococcal or fungal. The disclosure of moderate to large vegetations by two dimensional echocardiography is an indication for operation. PMID- 1495316 TI - Treatment of tachyarrhythmias in a patient with the long QT syndrome by autotransplantation of the heart and sinus node-triggered atrial pacing. AB - The case history of a 37-year-old woman with the long QT syndrome and drug refractory paroxysmal ventricular tachyarrhythmias is reported. She was resuscitated eight times between 1980 and 1987. The duration of these attacks increased from a few minutes to 8 hours and the interval between them decreased from 2 years to 4 weeks. An autotransplantation was performed of the anatomically and hemodynamically normal heart. She has had normal QT intervals and has been free of tachyarrhythmias since the operation in June 1987. Because of a slow escape low atrial rhythm, she was treated with a dual-chamber pacemaker programmed in the VDD mode with a coupling interval of 15 msec. The pacemaker wires were connected to the nontransplanted atrial cuff ("atrial" wire) and the transplanted atrium ("ventricular" wire). The hemodynamic effect of the resultant sinus node-driven low atrial pacing was restoration of normal values. This is the first report of successful autotransplantation of the heart for ventricular tachyarrhythmias caused by the long QT syndrome. PMID- 1495317 TI - Limitations and pitfalls in the assessment of prosthetic valves with Doppler ultrasonography. AB - Normal Doppler-derived data for new prosthetic designs are currently gathered after marketing. Therefore the cardiologist needing to assess a new valve may need to equate Doppler results with data gathered invasively during premarket testing. This invites error because catheterization and Doppler ultrasonography are not always directly comparable. This review discusses difficulties in defining normal prosthetic function and problems arising from the comparison of catheter and Doppler data. It concludes that (1) the hemodynamic formulas in current use have limitations when applied to normally functioning prosthetic valves, (2) patterns of normal regurgitation differ widely between different valve designs and may occasionally resemble paraprosthetic leaks, (3) there is a good case for reporting only raw Doppler data rather than derived pressure drop or effective orifice area, (4) a new prosthetic design should be tested in vivo with Doppler ultrasonography before marketing, and (5) nonprosthetic factors affecting Doppler data and flow information should always be given. PMID- 1495318 TI - Aortic valve infection. Risk factors for death and recurrent endocarditis after aortic valve replacement. AB - Patients (n = 195) undergoing aortic valve replacement (n = 209) for native or prosthetic valve endocarditis were studied to determine risk factors for death and recurrent endocarditis and also to determine the valve type least likely to be associated with recurrent endocarditis. Ten-year survival was 60%, the highest risk of dying occurring within the first 3 postoperative months. Risk factors for death in this early phase included increased urea concentration, higher New York Heart Association functional class, prosthetic valve endocarditis, infection status (lower in patients with healed endocarditis), longer duration of cardiopulmonary bypass, and nonuse of an allograft valve. In the late phase (beyond 3 months), risk factors included age at operation and Staphylococcus aureus infection (only in New York Heart Association functional class V). Ten years after aortic valve replacement, 79% of valves were free of recurrent endocarditis. The highest risk of recurrence was in the first 4 months. Longer duration of cardiopulmonary bypass was a weak risk factor for recurrent endocarditis in the early phase, and in the late phase risk factors were S. aureus infection (only in New York Heart Association functional classes III, IV, and V) and the use of now discontinued biologic valves. Allograft aortic valve replacement was shown to be associated with a low and constant risk of recurrent endocarditis, whereas other valve types were associated with a high early risk. The allograft valve should be the preferred replacement device for aortic root infection. PMID- 1495319 TI - Transesophageal color flow Doppler imaging for aortic insufficiency in patients having cardiac operations. AB - Transesophageal color flow Doppler findings were studied in 30 patients with aortic insufficiency who had cardiac operations. Measurements were expressed as ratios of corresponding left ventricular outflow tract dimensions. Regurgitant jet proximal width ratio was significantly related to jet area ratio (r = 0.92) and correlated poorly with the degree of jet penetration into the left ventricular cavity (r = 0.32). The vectors of the regurgitant jets were variable. Nine patients had undergone aortography. Regurgitant jet proximal width and area ratios were significantly related to angiographic grade (r = 0.88 and 0.87, respectively) in these patients. We concluded that the esophagus offers a satisfactory transducer orientation for color flow Doppler assessment of aortic insufficiency. PMID- 1495320 TI - Invited letter concerning: Changes in plasma-free thyroid hormones during cardiopulmonary bypass. PMID- 1495321 TI - The ALCAPA: what's in a name? PMID- 1495322 TI - Surgical closure of the defect in Fallot's tetralogy with the use of an aneurysm like membranous flap. PMID- 1495323 TI - Intraoperative placement of endovascular stents. PMID- 1495324 TI - Retrograde cerebral perfusion against massive air embolism during cardiopulmonary bypass. PMID- 1495325 TI - Myocardial protection or cerebral protection: a potential conflict. PMID- 1495326 TI - Underestimation of mitral regurgitation under general anesthesia. PMID- 1495327 TI - Complex cardiac wounds. PMID- 1495328 TI - Treatment of neurasthenia with electric plum-blossom needle therapy and observations of body surface reactions. PMID- 1495329 TI - Treatment of peripheral facial paralysis by scalp acupuncture--a report of 100 cases. PMID- 1495330 TI - 47 cases of migraine treated with acupuncture. PMID- 1495331 TI - Treatment of acute abdomen by electro-acupuncture--a report of 245 cases. PMID- 1495332 TI - A report of 22 cases of temporomandibular joint dysfunction syndrome treated with acupuncture and laser radiation. PMID- 1495333 TI - 100 cases of acute lumbar sprain treated with acupuncture at zhibian (UB 54). PMID- 1495334 TI - Acupuncture treatment of infantile diarrhea: a report of 1050 cases. PMID- 1495335 TI - Observations on the efficacy in treating scleritis by plum-blossom needle. PMID- 1495336 TI - Hypotensive effect of ototherapy in relation to symptomatic and dispositional types of patients. PMID- 1495337 TI - Effect of acupuncture on carbohydrate metabolism in patients with simple obesity. PMID- 1495338 TI - Acupuncture at otoacupoint heart for treatment of vascular hypertension. AB - The immediate, short-term and long-term depressor effects, the immediate effects on cardiac functions in grade II and grade III vascular hypertension, and the effects on angiotensin II in grade III vascular hypertension by acupuncture at otoacupoint Heart were studied in 30 cases of vascular hypertensive patients. The immediate depressor effect of acupuncture at otoacupoint Stomach was also recorded for comparison. It was found that acupuncture at otoacupoint Heart produced marked immediate depressor effect, and the short-term effective rate was 100%, the long-term effective rate was 63.3%, as well as evident immediate effects on cardiac functional activities in grade II and grade III hypertension and marked effects on angiotensin II in grade III hypertension. Acupuncture at otoacupoint Stomach produced no depressor effect on vascular hypertension. PMID- 1495339 TI - Effects of atropine on the changes of pain threshold and contents of leucine enkephalin and catecholamines of the brain in rats induced by EA. AB - After rats received electroacupuncture (EA), leucine-enkephalin (LEK) content in striatum and dopamine (DA) concentration in both brain stem and diencephalon markedly increased, and noradrenaline (NA) level in telencephalon definitely decreased with an obvious elevation of pain threshold. However, a previous intraperitoneal injection of atropine, a blocker of muscarinic receptor, not only partially blocked the analgesic effect of EA, but also changed the effects of EA on LEK, NA and DA contents of the brain. The results indicate that cholinergic system plays an important role in electroacupuncture analgesia (EAA), which may be fulfilled partially through the central LEK and catecholamine (CA) systems. PMID- 1495340 TI - Treatment of optic atrophy with acupuncture. PMID- 1495341 TI - Traditional Chinese methods of health preservation. PMID- 1495343 TI - A perspective of the clinical research on traditional Chinese medicine in the treatment of cardiovascular diseases in the 1990s. PMID- 1495342 TI - Clinical application of point-through-point acupuncture. PMID- 1495344 TI - Clinical observations on the anti-rejection effect of Chinese drugs in homografting of pancreatic islets. PMID- 1495345 TI - Electroacupuncture treatment of presenile and senile depressive state. PMID- 1495346 TI - Suspended moxibustion of ignited moxa roll in treating coronary heart disease: a clinical observation of 138 cases. PMID- 1495347 TI - Esthesioneuroblastoma: the UCLA experience 1970-1990. AB - A retrospective review was conducted of all esthesioneuroblastoma cases treated at UCLA Medical Center from 1970 through 1990. Patients were staged according to the staging systems of Kadish, et al., Biller, et al., and a new staging system proposed by the authors. Of 26 patients treated, 74% were alive at 5 years and 60% were alive at 10 years. Combined treatment with surgery and radiation is advocated since a recurrence-free status was achieved in 92% of the patients, compared with 14% for surgery alone and 40% for radiation alone. A craniofacial resection was performed in 7 patients, all of whom have remained disease free. Negative prognostic factors included: age over 50 years at presentation, female sex, tumor recurrence, and metastasis. The proposed new staging system predicted disease-free status better than the other staging systems. PMID- 1495348 TI - Thin malignant melanomas of the head and neck. AB - Historically, Breslow classified thin melanomas as invasive lesions less than 0.76 mm in depth with rare instances of recurrence and mortality. From 1970 to 1990, 87 patients with thin head and neck melanoma were treated at Duke Medical Center. A computer-aided retrospective analysis was performed. Recurrence occurred in 30% of these patients; however, of the 66 patients seen at this institution prior to recurrence, only 8% recurred. Recurrence significantly shortened survival. Compared to an overall 84% 5-year survival, there was less than a 50% 5-year survival after recurrence. For thin melanomas, thickness did not affect survival. There was no difference in survival between thin melanomas and those ranging from 0.76 to 1.5 mm. A multivariate analysis was performed. The data suggest that thin melanomas of the head and neck may recur at a higher rate than previously reported and in addition, that they can be lethal. PMID- 1495349 TI - Ornithine decarboxylase activity in tumor and normal tissue of head and neck cancer patients. AB - Tumorigenesis requires increased biosynthesis of polyamines and elevated levels of ornithine decarboxylase, which is the rate-limiting enzyme in the polyamine synthesis pathway. Previous animal studies have noted a marked increase in ornithine decarboxylase after exposure to tumorigenic stimuli and that pretreatment with vitamins A and E provides protection against the carcinogenic action. However, studies of ornithine decarboxylase activity in human oral cavity carcinoma have not been as specific. The goal of this study was to determine whether a specific difference in ornithine decarboxylase activity occurs in tumor versus adjacent normal tissue in head and neck squamous cell carcinoma patients. Ornithine decarboxylase activity was measured in 30 consecutive head and neck cancer patients undergoing surgical therapy. Ornithine decarboxylase levels were found to be significantly elevated in tumor tissue samples when compared to adjacent normal mucosa samples (P less than .004). This finding confirms the previous findings noted in animal models and implies that the protective effects of vitamins A and E will extend to human head and neck cancers. PMID- 1495350 TI - Laryngeal chondrosarcomas: a clinicopathologic study of 11 cases, including two "dedifferentiated" chondrosarcomas. AB - Laryngeal chondrosarcomas are uncommon, and those that contain a distinct, nonchondroid, high-grade spindle cell sarcoma (the so-called "dedifferentiated" chondrosarcoma or chondrosarcoma with additional malignant mesenchymal component [CAMMC]) are extremely rare. Laryngeal CAMMC merit special attention, as CAMMC in other sites portends a poor prognosis. Eleven patients with laryngeal chondrosarcomas are reported on; 2 of these patients had CAMMC. On follow-up, 3 of the 11 patients had recurrences. The first had recurrence 4 and 11 years after tumor enucleation; that patient died disease free 2 years after salvage total laryngectomy. The second had recurrence 2 years after partial laryngectomy and was lost to follow-up after salvage total laryngectomy. The last patient recurred 13 years after partial laryngectomy and underwent salvage total laryngectomy; that patient was one of the two who developed CAMMC, and he also developed stomal recurrence of the "dedifferentiated" component 3 years after total laryngectomy. The other 8 patients are disease free after partial laryngectomy (6) or total laryngectomy (2) 10 months to 12 years later (mean: 51 months). This includes the 1 other patient with CAMMC, who is disease free 60 months after total laryngectomy. Laryngeal CAMMC has been shown, in at least one of the two patients, to be associated with a poor outcome. Patients with recurrent laryngeal chondrosarcomas do not have a poorer outcome after salvage total laryngectomy. The authors advocate partial laryngectomy if technically feasible. PMID- 1495352 TI - Gross morphologic and functional effects of postoperative radiation on free jejunal autografts. AB - Twenty adult mongrel dogs underwent free jejunal transplants to the neck; 10 either died of or had to be sacrificed as a result of postoperative complications, 5 received a 55-Gy-equivalent dose of radiation after 3 weeks, and 5 were followed as controls. Serial manometric and endoscopic evaluations were performed over a 9-month period. Progressive deterioration of the quality and amplitude of peristalsis of the jejunal autografts was observed only in the radiated group. In addition, all dogs in the radiated group developed severe jejunal circumferential constriction and stricture formation. These delayed effects of irradiation on revascularized jejunal autografts should be considered in planning the method of pharyngoesophageal reconstruction as well as the timing of adjuvant radiotherapy. PMID- 1495351 TI - Biodistribution of rhodamine-123 in nude mice heterotransplanted with human squamous cell carcinomas. AB - Rhodamine-123 uptake and release was determined in nu/nu mice heterotransplanted with P3 human squamous carcinomas to assess its value as an in vivo laser photosensitizer for treatment of solid tumors. Following intraperitoneal injection of Rh-123 (1 micrograms/g of body weight), mice were killed at 2, 4, 6 and 24 hours, and 3 and 7 days postinjection. The peak concentrations of Rh-123 per milligram of tissue measured by fluorescence spectrophotometry was distributed as follows: kidneys greater than spleen greater than intestine greater than stomach greater than liver greater than tumor greater than skin greater than skeletal muscles greater than lung greater than heart greater than blood greater than brain. No preferential uptake or retention of Rh-123 by tumors was observed. However, a longer retention with higher concentrations of the dye was seen in normal skin as opposed to P3 tumors from 4 hours to 7 days postinjection with Rh-123. The elimination of Rh-123 was rapid, with the dye falling to less than 2% of peak concentration at 7 days postinjection. Knowledge of Rh-123 biodistribution in tumors and other tissues suggests that optimal timing after injection of this dye may allow selective photodiagnosis and photodynamic therapy of tumors with the argon laser. PMID- 1495353 TI - Postoperative radiation therapy for cervical lymph node metastases from an occult squamous cell carcinoma. AB - One hundred thirteen patients with cervical metastases from a squamous cell carcinoma and no evidence of the primary tumor were treated for cure by surgery and routine large-field postoperative irradiation. Patients were staged according to the 1987 American Joint Committee on Cancer (AJCC) classification. There were 24 N1, 54 N2, 29 N3, and 6 Nx lesions. One hundred four patients underwent cervical lymph node dissection and 9 had adenectomy. All patients received postoperative external beam therapy to the entire naso-oro-pharyngo-larynx and all cervical lymphatics. The overall nodal failure rate was 13.7%. Nodal failure was significantly correlated with N staging (P = .01) and with the number of histologically involved nodes (P = .05). NOdal failure was 21% when nodes were initially fixed versus 7.5% when they were not (P = .07) and 18% when there was extracapsular spread versus 4.3% when the capsule was intact (P = .11). Eleven patients (9.7%) developed a subsequent primary lesion. In 3 patients (2.6%), this primary was located in the previously irradiated area and, in 2 cases, under the anterior block of lateral fields. Metastases occurred in 18 patients (16%). The five-year overall survival rate was 38%. Survival was correlated with N staging (P less than .02), nodal fixation (P = .05), extracapsular spread (P = .01) and loosely with the number of histologically involved nodes (P = .08). On the contrary, histological differentiation did not influence the local control rate, nor the development of metastases or subsequent primary lesions. Large-field prophylactic radiation therapy appears to be effective in preventing the emergence of initially occult primary lesions. However, control of disease in the neck and survival remain disappointing in patients with advanced nodal disease, even after combined surgery and radiation therapy. PMID- 1495354 TI - Neoplastic infiltration of laryngeal cartilages: histocytochemical study. AB - The relationship between cartilage and invading neoplastic cells was studied in 32 cases of laryngeal cancer by histological and cytochemical methods. Cartilage invasion was present in 12 cases, 10 of which were in proximity or in contact with areas of calcification and ossification. It was significantly correlated only to tobacco consumption (P less than .05) and, in regard to glottic tumors, to tumor diameter greater than 3 cm (P less than .01). Histologically, neoplastic invasion in cartilage was massive in 2 cases, occurred in areas of ossification in 4, between cartilage and bone in 4, and in epiglottic cartilage in 2. In 3 of the cases with bone invasion, there was also new bone formation. Hyaline cartilage and bone resorption was due to tartrate-resistant acid phosphatase (TRAP)-positive giant cells; in epiglottic cartilage only mononuclear cells were present, some of which were TRAP-positive. These results show that neoplastic cells can promote not only resorption and formation of bone, but also resorption of cartilage, which is considered resistant to neoplastic invasion. The different types of resorbing cells in contact with hyaline cartilage and bone in laryngeal cancer, and elastic cartilage in epiglottic cancer, suggest that the structure of the tissue being resorbed can influence the type of resorbing cells. PMID- 1495355 TI - T1 squamous cell carcinoma of the arytenoid. AB - Twenty-two cases of early squamous cell carcinoma of the arytenoid cartilage staged as T1 according to the 1983 American Joint Committee for Cancer Staging Classification system were reviewed. Eighteen percent of the patients showed no symptoms. In the remaining 82%, the main presenting symptom was pain in the form of sore throat, odynophagia, or otalgia. Radiotherapy and partial laryngeal surgery were the options retained for the treatment of the larynx. A "watch and wait" policy or preventive treatment of the ipsilateral jugulocarotid lymph nodes were the treatment options retained for the neck. Significant differences were noted in terms of local and nodal recurrence between the two programs. Results indicate that partial laryngeal surgery with total arytenoidectomy and preventive treatment of the neck appear to be advisable for this particular type of primary lesion. PMID- 1495356 TI - Results of endoscopic sinus surgery for the treatment of inverted papillomas. AB - Fifty-one patients suffering from inverted papillomas of the nose and paranasal sinuses were reexamined in a retrospective study. Thirty-five had undergone surgery by an intranasal endoscopic approach and 16 had undergone surgery by an extranasal approach. The recurrence rate following endoscopic interventions was 17% (6/35), as compared to 19% (3/16) after extranasal operations. Endoscopic surgery proved to be successful even in the treatment of large lesions affecting the posterior ethmoidal sinus, the nasofrontal duct, or the sphenoidal sinus. Its indication thus no longer needs to be restricted to limited lesions of the anterior nasal cavity. Patients with inverted papillomas will benefit from this surgical technique which remains minimally invasive and thus retains the paranasal bony framework, preserves unaffected mucosa capable of recovery, and prevents damage to the patients' cosmetic features. PMID- 1495357 TI - Effectiveness of salvage neck dissection for advanced regional metastases when induction chemotherapy and radiation are used for organ preservation. AB - The recently completed VA Cooperative Study (CSP #268) of induction chemotherapy (cisplatin/5-FU) and definitive radiation (6600 to 7600 cGy) for organ preservation in advanced (stage III or IV) laryngeal cancer demonstrated that, although larynx preservation could be achieved in 64% of randomized preservation could be achieved in 64% of randomized patients, overall survival rates were not improved over conventional treatment (surgery/postoperative radiation). Of 166 patients randomized to induction chemotherapy, 46 had N2 or N3 disease and were analyzed to determine the effectiveness of the organ preservation treatment strategy on control of neck disease and survival. The clinical response of neck metastases to induction chemotherapy was significantly associated with subsequent salvage neck dissection (P = .008). The overall death rate was increased (P = .014) and survival time decreased in patients with less than a complete response in the neck after chemotherapy (P = .15). This was related primarily to failure to control the disease in the neck. The overall survival of patients achieving a complete response in the neck was improved over the randomized group of N2 or N3 patients treated with primary surgery. The findings suggest that response of neck nodes should be assessed independently of primary tumor response in trials of organ preservation strategies using induction chemotherapy, and that failure to achieve a clinical complete response in the neck warrants planned early salvage neck dissection in order to achieve improved overall survival. PMID- 1495358 TI - Zenker's diverticulotomy using the KTP/532 laser. AB - Multiple forms of surgical treatment exist for Zenker's diverticulum. Appropriate treatment needs to be tailored based on the needs of the patient and the resources and skills of the surgeon. We have reviewed the available surgical options and presented a series of 10 patients treated with a new technique, the KTP/532 laser diverticulotomy. The diverticulotomy is particularly well-suited to the debilitated patient who cannot tolerate a prolonged operation or a prolonged postoperative recovery. The results of the technique are comparable with those of other forms of diverticulotomy, and it is concluded that the KTP/532 laser is a simple, safe, and effective form of surgical treatment with exciting potential for future use. PMID- 1495359 TI - Transnasal septal displacement approach for secondary transsphenoidal pituitary surgery. PMID- 1495360 TI - Percutaneous tracheotomy. PMID- 1495361 TI - Percutaneous tracheotomy. PMID- 1495362 TI - Improving teaching Valsalva's maneuver. PMID- 1495363 TI - Transurethral incision of the prostate using the holmium:YAG laser. AB - Transurethral incisions of the prostate were made endoscopically in 5 dogs under a fluid medium using a holmium:YAG (Ho:YAG) laser operating at a wavelength of 2.1 microns and with delivery of 1.0 J/pulse in 15 Hz (15 W). Histopathologic examination of tissues collected immediately after surgery revealed irregular crevices outlined by a narrow zone of coagulative necrosis. Ulcerated fissures persisted at 5 and 7 days with the initial stages of epithelial regeneration partially re-epithelializing the ulcerated surfaces. A modest inflammatory response characterized by edema, hemorrhage, and a mixed inflammatory cell infiltrate was also associated with the laser incision sites at 5 and 7 days. Three weeks postlasing, the ulcerated surfaces of the fissures were completely re epithelialized. At 5 weeks only a slight indentation persisted at the incision sites with minimal changes in the subjacent submucosa and prostatic glandular architecture. Although the results of these investigations are preliminary, we believe that the Ho:YAG laser warrants further clinical evaluation for treating patients with benign prostatic hyperplasia (BPH), urethral strictures, bladder neck contractures, and constrictions of the upper urinary tracts. PMID- 1495364 TI - Neodymium:YAG laser treatment of bladder neck contracture following prostatectomy. AB - A total of 21 patients with postprostatectomy bladder neck contracture underwent treatment with Nd:YAG laser irradiation. A new 800-microns hemispherical optical quarz fiber was used in contact technique to produce linear incisions in the scarred tissue. Within 11.2 months, median of follow-up, there was improvement in the obstructive voiding symptoms in all the patients. Two patients who had still mild contracture in the first follow-up cystoscopy were managed successfully with a second treatment. Endoscopic application of laser energy in the contact mode enables the immediate vaporization and disintegration of the fibrous area and secondary reepithelization of the bladder neck without scarring. PMID- 1495365 TI - Erb:YAG and Hol:YAG laser ablation of meniscus and intervertebral discs. AB - Erb:YAG and Hol:YAG laser ablation rates of fibrocartilage and nucleus pulposus were measured in vitro simulating clinical conditions. After ablation macroscopic and microscopic appearance of the ablation site was investigated. Hol:YAG and Erb:YAG laser mean ablation rates increased almost linearly with rising energies, showing higher total ablation rates for the Hol:YAG laser due to its higher achievable energy density. At comparable energy densities the Erb:YAG laser appears to be more effective with respect to the corresponding ablation rates. Consequently, the ablational threshold proved to be lower for the Erb:YAG laser. Whereas during Hol:YAG laser ablation, some smoke formation and considerable tissue shrinking occurred, these effects could not be observed during Erb:YAG laser ablation. Consequently macroscopic and microscopic inspection showed some thermal damage after Hol:YAG and only minimal alterations after Erb:YAG laser ablation. Adjacent thermal damage was determined and proved to be lower for the Erb:YAG laser. In our opinion the characteristics of each laser system provide certain advantages for special clinical indications. PMID- 1495366 TI - Holmium-laser synovectomy of immune synovitis in rabbits. AB - Holmium-laser synovectomy was carried out to remove allergically inflamed synovial membranes in rabbit knee joints. The healing process was then investigated at different periods. Left knee joints of 12 rabbits were exposed to Ho:YAG-laser radiation at a wavelength of 2.1 microns, pulse energy of 600 mJ, pulse length of 1 ms, and repetition rate of 3 Hz. Twelve others were treated conventionally and 12 served as controls. After 1 day, 1 week, and 1 and 3 months, respectively, 3 animals from each group were sacrificed and the synovialis grossly and microscopically examined. Coagulation necrosis, inflammation, and edema resulted following laser therapy. After 1 week, the synovial layer consisted of a scarlike formation of fibers and within 1 month, its surface appeared smooth. The mechanical abrasion caused hemorrhage and necrosis. Fibrosis developed in the capsular layers, and after 3 months, the surface appeared coarse and villous. Based on these preliminary findings, holmium laser synovectomy may offer an alternative method to existing therapeutic techniques. PMID- 1495367 TI - Photoacoustic injury and bone healing following 193nm excimer laser ablation. AB - The argon-fluoride excimer laser was investigated as a cutting-ablating tool for bone surgery. A total of 52 rats were divided into two experimental groups and two control groups. In one experimental group cortical bone defects were made; in another experimental group defects penetrating into the medullary space were performed. In the two control groups similar defects were achieved using water cooled carbide burs. The rats were sacrificed on each of the 3, 7, 10, 20, 30, and 40 postoperative day. The cortical bone, the medullary space, and the extrabony tissue were examined by means of light microscopy. In both experimental groups, bone damage, represented by osteocyte destruction, extended to 1,050 1,450 microns ahead from the irradiated site, and bone healing was very much impaired. In the control groups no histological changes could be identified and bone healing appeared to be within normal limits. We believe this extensive bone damage, following 193 nm irradiation, to be a result of photoacoustic waves propagating in the bone following each pulse. In view of our results we feel that excimer lasers presently in use are not suitable for bone surgery. This problem of photoacoustic damage can be overcome in one of two ways: by designing a CW excimer laser or by reducing the pulse width to the picosecond regime. PMID- 1495368 TI - Feasibility of skin deepithelialization using the contact neodymium-yttrium aluminum-garnet laser. AB - In a manner similar to laserbrasion, the carbon dioxide (CO2) laser has a proven role for expediting skin deepithelialization, which is an essential component of many reconstructive procedures. However, the contact Neodymium-Yttrium-Aluminum Garnet (Nd:YAG) laser has many additional attributes such as tactile feedback and less plume that theoretically offer an advantage over the CO2 laser for this adjunctive maneuver. In rat experimental models and clinical applications, removal of the epidermis necessary for skin deepithelialization may indeed be achieved using a rounded probe for vaporization with the contact Nd:YAG laser. Unfortunately, the length of time necessary for skin deepithelialization with the Nd:YAG laser exceeded even conventional methods, such that this role with the present technology, although possible, is inefficient and impractical. PMID- 1495369 TI - Effects of coaxial CO2/Nd:YAG irradiation on periodontal wound healing. AB - This study evaluated a coaxial CO2/Nd:YAG laser used during periodontal surgery in mongrel dogs for the purpose of ablating the osseous portions of root surfaces to increase reattachment of soft tissue. Periodontal defects were produced with ligatures of orthodontic wire and elastics. The left mandibular osseous root surfaces were irradiated with a defocused, CW laser beam [power density (PD) = 42.46 W/cm2, energy density (ED) = 424.63 J/cm2]. The left maxillary osseous root surfaces were treated with a beam at twice the energy density [PD = 84.93 W/cm2, ED = 849.3 J/cm2]. The mandibular right quadrant received conventional surgery and the maxillary right quadrant served as the untreated control. Fourteen days after treatment, facial/lingual attached gingivae were scored for soft tissue adherence to bone. Laser irradiation at low ED did not improve soft tissue attachment when compared to conventional treatment. Higher ED irradiation produced significantly less attachment and increased tissue necrosis. PMID- 1495370 TI - Microprocessor-controlled Nd:YAG laser for hyperthermia induction in the RIF-1 tumor. AB - Near-infrared radiation from a Nd:YAG laser at 1,064 nm was used interstitially or superficially to induce hyperthermia in RIF-1 tumors in C3H male mice. A single 600-microns quartz fiber with a 0.5-cm cylindrical diffusor or a weakly diverging microlens at its distal end was used to deliver laser energy to tumors in the hind leg (mean volume = 100 mm3). Two thermocouples were inserted into each tumor. One thermocouple controlled a microprocessor-driven hyperthermia program (maximum output of 3.5 Watts) to maintain the desired temperature. Tumors were exposed to various temperature-time combinations (42-45 degrees C/30 min). Our initial results indicated that excellent temperature control to within 0.2 degrees C of the desired temperature at the feedback thermocouple was achievable during both superficial and interstitial heat treatments. Temperatures at the second thermocouple, however, were found to be lower by as much as 2.3 degrees C (using the cylindrical diffusor) or higher by up to 4.6 degrees C (using the microlens) when compared to the feedback thermocouple temperature. Several correlations were seen between total dose, tumor growth delay, percent skin necrosis, and temperature at the second thermocouple after several superficial and interstitial treatments. Statistically significant improvements in tumor growth delay (at 42 and 45 degrees C) and increased percent skin necrosis at all temperatures were observed after superficial versus interstitial treatment. PMID- 1495371 TI - Interstitial photoradiation injury of normal brain. AB - The effect on normal brain of continuous interstitial laser irradiation at 630 nm through an implanted cylindrical-shape, diffusion-tipped optical fiber was studied in the rat. Brain water content in the laser irradiation area (LIA) and Evans blue (EB) dye content in selected areas of the brain were measured for different laser power outputs from 0 to 250 mW after 5 minutes of photoradiation. The degree and nature of tissue damage was examined histologically and correlated with the laser power level. There is significant brain damage, blood brain barrier (BBB) disruption, and brain edema in LIA for laser power outputs in excess of 100 mW from the diffusion tip (p less than 0.001). Brain edema in the LIA is strongly correlated with BBB disruption indicated by the presence of EB. Histologically, the cortical surface was more susceptible than deeper white matter regions to interstitial laser irradiation. Possible indirect mechanisms of brain injury from interstitial laser irradiation are discussed. PMID- 1495372 TI - Therapeutic effect of Ga-Al-As diode laser irradiation on experimentally induced inflammation in rats. AB - We produced experimental inflammation models in rats by carrageenin and studied the effect of Ga-Al-As diode laser irradiation (780 nm, continuous wave, 31.8 j/sec/cm2, spot size of 0.2 mm) on inflamed regions compared with those of indomethacin, a potent anti-inflammatory agent. We found that a low-power infrared laser has an anti-inflammatory effect on carrageenin inflammation. A low power laser inhibits: (1) the increase of vascular permeability during the occurrence of an acute inflammation in the carrageenin-air-pouch model, (2) edema in the acute stage in the carrageenin-paw-edema model, and (3) the granuloma formation in the carrageenin-granuloma model after receiving laser irradiation once daily. In all cases, irradiation for less than 10 min was sufficient to inhibit the inflammation by 20-30%. The inhibitory effect of laser irradiation was not comparable to that of indomethacin (4 mg/kg, i.o.) in the air-pouch model and the paw-edema model, whereas laser irradiation was more potent than that of daily administration of indomethacin (1 mg/kg, i.o.) in the granuloma model. In future studies of the mechanism of laser effect, it should be noted that irradiating a rat twice, before and after the provocation of inflammation, was essential in order to achieve an effective inhibition of paw-edema. PMID- 1495373 TI - Dye-mediated bactericidal effect of He-Ne laser irradiation on oral microorganisms. AB - Little attention has been given to the bactericidal effect of laser irradiation, particularly using low-power energy lasers. It has been demonstrated that He-Ne laser light has an inhibitory action on dental plaque. The purpose of this study was to investigate the bactericidal effect of He-Ne laser irradiation on cariogenic microorganisms. The bactericidal effect was determined by the formation of a growth-inhibitory zone or by the counting of viable bacterial colonies. Streptococcus sobrinus AHT that is a Gram-positive microorganism was sensitive to He-Ne laser light, but Escherichia coli, a Gram-negative microorganism, was resistant. The effect of several dyes necessary to instigate a bactericidal action was also examined. A growth-inhibitory zone was observed using 10 kinds of blue, purple, or green dyes, which were mainly phenylmethane dyes. The leakage of potassium from S. sobrinus AHT following laser irradiation was determined using an atomic absorption spectrophotometer. The leakage began to increase following irradiation for 2 min, and reached a plateau following irradiation for 30-60 min. Moreover, to examine some changes in the dye itself following laser irradiation in the absence of bacteria, ultraviolet-visible absorption spectra and 1H NMR spectra were recorded. In this study, it was indicated that the bactericidal effect on cariogenic bacteria by He-Ne laser irradiation was efficient only in the presence of specific dyes. It is suggested that this laser may be suitable for clinical applications in preventive dentistry. PMID- 1495374 TI - Role of immersion refractometry for investigating laser-induced effects in cells. AB - The broad background of scattered light observed in spectra of cell suspensions is reduced by factors of up to 20 by immersion refractometry allowing for improved spectroscopic determination of the absorption properties of cells in the 325-820 nm range. Refractive-index matched spectra of E. coli C1a exhibit a set of resonant features near 422, 561, and 582 nm. Exposure wavelengths are chosen based on this spectrum and cell viability is investigated in E. coli suspensions exposed to 350, 400, 422, 440, and 700 nm radiation delivered in nanosecond pulses with total doses from 500 millijoules to 60 Joules. We observe a loss in cell viability for doses greater than 1 Joule at 422 nm and for all doses at other wavelengths; exposures of less than 1 Joule at 422 nm enhance growth. Excluding exposures at wavelengths within the resonant feature, longer wavelengths are less effective at reducing the viability of E. coli C1a. This indicates the occurrence of at least two absorption processes. PMID- 1495375 TI - Forearm flap in orthopaedic and hand surgery. AB - This study was undertaken in order to evaluate the usefulness of the forearm flap in reconstruction of severe injuries of the upper and lower extremities. A total of 34 patients with extensive skin defects of the upper and lower extremities were treated using radial forearm flaps during the last 4 years. Twenty-four patients had lower extremity injuries, while the remaining ten had upper extremity reconstruction. In two patients, the radial forearm flap was used as an island flap in retrograde direction for coverage of skin defects of the dorsum of the hand. In two patients, the palmaris longus tendon was included in the flap to reconstruct the extensor tendon of the index finger. In one patient, it was used as an innervated flap to cover a skin neurotrophic defect of the sole of the foot. None of the patients had the bony portion of the radius included. Of the 34 flaps, 29 survived. Of the remaining 5, 3 failed totally and 2 partially. The 2 partially failed flaps required reoperation and revision of the venous anastomosis, which was found to be occluded. The patients, eight women and twenty six men, were examined and questioned regarding the cosmetic appearance of the donor site. The final cosmetic appearance was acceptable to all patients. We conclude that the radial forearm flap is a useful, easily elevated flap, suitable for skin defects of upper and lower extremities. Major advantages of the flap are its ability to be used as an island flap and that the surgery can be performed under axillary block anaesthesia. PMID- 1495376 TI - Results after repair of traumatic arterial damage in the forearm. AB - Eighty-three patients, with 96 instances of radial or ulnar arterial damage, were treated over a four-year period using microsurgical techniques. Thirty-one patients, with 43 arterial repairs, were available for evaluation. In the 14 patients with a single arterial repair, 4 resulted in thrombosis (71.5% success rate). When both arteries required repair, our success rate was 75.9%, with 7 thromboses. The overall success rate was 74.5%. We attribute the high patency rate to strict microsurgical technique, the repair of the vessels in the early stages after trauma, and the use of vein grafts after complete resection of the damaged portion of the vessel. PMID- 1495377 TI - Clinical analysis and evaluation of the function of replanted and revascularized parts of the upper limb. AB - During the past four years, we have attempted to replant and revascularize 57 hands and fingers in 43 patients. The total success rate was 81%. Replantation of hands severed cleanly (guillotine type) and those with slight local crush injuries had the highest success rate. As for hand function, amputations at zones III and IV with end-to-end suturing of the tendons and nerves presented the highest degree of function when evaluated objectively and subjectively. All patients presented a high degree of satisfaction with the outcome of the operation. PMID- 1495378 TI - Free vascularized fibular graft: a versatile graft for reconstruction of large skeletal defects and revascularization of necrotic bone. AB - The microvascular transfer of a fibular graft that was initially introduced for the treatment of massive bone loss in the appendicular skeleton has more recently found another useful application in the management of the osteonecrosis of the femoral head. Since 1989, we have successfully used the free vascularized fibula in two patients with segmental bone loss, one in the forearm and the other in the distal femur. We have also attempted revascularization of the femoral head in fifteen patients (eighteen hips) with osteonecrosis. Although our follow-up is short, the results have been encouraging and this method is now the treatment of choice in the early stages of the disease. PMID- 1495379 TI - Use of free flaps in the aesthetic reconstruction of face and neck deformities. AB - Three cases of face and neck deformities, reconstructed with free flaps in order to obtain better aesthetic results, are presented here. Nasal tip, cartilage, and soft tissue defects as well as facial burn contractures were reconstructed with a free radial forearm flap, latissimus dorsi myocutaneous flap, and groin flap, respectively. Case specifics are discussed. PMID- 1495381 TI - Experimental evaluation of the length of microvenous grafts under normal tension. AB - Four groups of microvenous grafts of 2, 4, 6, and 10 cm were used to determine whether length under normal tension affects patency rates in bridging arterial defects. Tension was evaluated by allowing the grafts to assume their normal orientation and length by filling them with blood, under physiological pressure, after the completion of the proximal anastomosis. The length was estimated through the normal range of motion such that the graft would not be too loose and/or tortuous following final anastomosis. The patency rates in the four length groups of this study ranged between 80% and 83%, with no statistical difference between groups. No statistically significant correlation was found between graft length and patency rate. It was concluded that the length of venous autografts does not affect patency. PMID- 1495380 TI - Post-discectomy perineural fibrosis: comparison of conventional versus microsurgical techniques. AB - The lumbar spines of twenty-one dogs were used as an experimental model. The animals were divided into three groups. In the first group, selective damage to the perimeningeal blood vessels was induced and the resultant hematoma was left untouched in the spinal canal. In the second group, the posterior longitudinal ligament was incised, and in the third group, the posterior longitudinal ligament was incised and damage induced to the perimeningeal blood vessels. The pathology examination revealed: (1) the hematoma itself did not lead to the formation of perineural fibrosis, (2) the incision of the posterior longitudinal ligament led to the formation of a limited amount of fibrosis, and (3) the coexistence of hematoma and incision of the posterior longitudinal ligament led to the formation of extensive perineural fibrosis. When discs are removed using microsurgical techniques, it is possible to avoid the formation of the postoperative hematoma and consequently to eliminate the perineural fibrosis. PMID- 1495382 TI - Hemodynamic and histological differences in end-to-side anastomoses. AB - An end-to-side anastomosis is often a necessity in replantation surgery. This study examines the effects of elliptical versus slit arteriotomy and the angle of anastomosis on vessel patency and aneurysm formation. Forty male rats were divided into four groups of ten rats each. The right and left common iliac arteries were selected as a model. The results showed no significant statistical difference in patency rates among our four experimental groups. The end-to-side anastomotic technique of choice uses the elliptical arteriotomy placed at a 90 degrees angle. It provides good visualization and easy suture placement. PMID- 1495383 TI - Cutaneous trunci myocutaneous flap: a new and reliable model for muscle free flap research in the rat. AB - This paper deals with the first myocutaneous flap in the rat. It is located just caudal to the axilla and consists of the insertion of the cutaneous trunci muscle with overlying subcuticular fat and skin and is supplied by the lateral thoracic vessels. It exhibits an all-or-none survival pattern. Because the skin can serve as a marker for muscle viability, we believe that this flap has great potential in future free muscle research. PMID- 1495384 TI - Free flap transfer of the cutaneous maximus muscle in the rat: comparison to the latissimus dorsi muscle flap. AB - A new rat model of free muscle flap transfer is presented. Microvascular transplantation of the cutaneous maximus muscle flap is performed at the groin site, with anastomosis of the axillary vessels to the appropriate femoral vessels. This muscle flap has many useful attributes for experimental manipulation. It has a high success rate following transplantation, the anatomy is consistent, the dissection is straightforward, the length of pedicle is relatively long (10 mm), the vessels for repair are of sufficient size (1.0-1.35 mm diameter), and the microsurgical procedure can be performed in a relatively short period. The donor site deficit causes minimal impairment to animal mobility, and no evidence of limb ischemia is noted after ligation of the axillary vessels. The cutaneous area adjacent to the muscle is perfused by muscular perforators supplied by the flap pedicle; thus a skin island may be used to monitor the flap or to create a composite myocutaneous transfer. The cutaneous maximus muscle has mixed muscle types and anatomic dimensions similar to those of the latissimus dorsi muscle, and it provides ample tissue for pharmacological and biochemical studies, yet it presents easier dissection and microanastomoses than the latissimus flap, with more potential for versatility in application. The advantages of this muscle flap make it a very useful experimental model for flap transfer research. PMID- 1495385 TI - Prefabrication of free flaps using the omentum in rats. AB - The omentum used as a vascular carrier is a new experimental model for prefabrication of free flaps in the rat. A 2.5 x 4 cm patch of omentum with gastroepiploic vessels and its rich vascular arcades was transferred under a bipedicled 2.5 x 6 cm right abdominal panniculocutaneous flap. At subsequent time intervals (postoperative days 0, 3, 5, 7, and 14), the skin pedicles were divided and the skin flap was raised as a composite island flap vascularized only by the underlying omental patch. The composite flap was then sutured back in place. Prefabricated flaps examined postoperatively demonstrated a dye fluorescence index (DFI) of 4.60% +/- 2.82% and 1.67% +/- 4.08% flap survival (FS) in the day 0 group; in the day 3 group, 9.83% +/- 1.47% of DFI and 15.00% +/- 10.35% of FS; in the day 5 group, 28.39% +/- 5.25% of DFI and 86.0% +/- 12.74% of FS (P less than 0.05); in the day 7 group, 38.19% +/- 7.52% of DFI and 98.13% +/- 3.72% of FS (P less than 0.05); and, in the day 14 group, 49.55% +/- 6.70% of DFI and 100% of FS (P less than 0.05). India-ink injection and histologic examination confirmed revascularization of the overlying skin by day 5. PMID- 1495386 TI - Amino acid sequences of several Bacillus subtilis proteins modified by apparent guanylylation. AB - Bacillus subtilis cell extracts, prepared at different times during growth, contained several proteins that were apparently guanylylated in vitro with [alpha 32P]-GTP. Four of the proteins were partially purified and the N-terminal amino acid sequences (13 to 20 residues) were determined. One sequence had 84% identity to Bacillus stearothermophilus triosephosphate isomerase, two were 100% identical to the predicted sequences of the B. subtilis ptsI and ptsH genes while no identity was found for the fourth sequence. This apparent guanylylation occurred with proteins involved in glucose metabolism, although the significance is unknown. PMID- 1495387 TI - Co-ordinate expression of virulence genes during swarm-cell differentiation and population migration of Proteus mirabilis. AB - The uropathogenic Gram-negative bacterium Proteus mirabilis exhibits a form of multicellular behaviour termed swarming, which involves cyclical differentiation of typical vegetative cells into filamentous, multinucleate, hyperflagellate swarm cells capable of rapid and co-ordinated population migration across surfaces. We observed that differentiation into swarm cells was accompanied by substantial increases in the activities of intracellular urease and extracellular haemolysin and metalloprotease, which are believed to be central to the pathogenicity of P. mirabilis. In addition, the ability of P. mirabilis to invade human urothelial cells in vitro was primarily a characteristic of differentiated swarm cells, not vegetative cells. These virulence factor activities fell back as the cells underwent cyclical reversion to the vegetative form (consolidation), in parallel with the diagnostic modulation of flagellin levels on the cell surface. Control cellular alkaline phosphatase activities did not increase during differentiation or consolidation. Non-flagellated, nonmotile transposon insertion mutants were unable to invade urothelial cells and they generated only low-level activities of haemolysin, urease and protease (0-10% of wild type). Motile mutants unable to differentiate into swarm cells were comparably reduced in their haemolytic, ureolytic and invasive phenotypes and generated threefold less protease activity. Mutants that were able to form swarm cells but exhibited various aberrant patterns of swarming migration produced wild-type activities of haemolysin, urease and protease, but their ability to enter urothelial cells was three- to 10-fold lower.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1495388 TI - The role of the pro-sequence in the processing and secretion of the thermolysin like neutral protease from Bacillus cereus. AB - The Bacillus cereus cnp gene coding for the thermolysin-like neutral protease (TNP) has been cloned, sequenced, and expressed in Bacillus subtilis. The protease is first produced as a pre-pro-protein (M(r) = 61,000); the pro-peptide is approximately two-thirds of the size of the mature protein. The pro-sequence has been compared with those of six other TNPs, and significant homologies have been found. Additionally, the TNP pro-sequences are shown to be homologous to the pro-sequence of Pseudomonas aeruginosa elastase. A mutant has been constructed from cnp, in which 23 amino acids upstream from the pro-protein processing site have been deleted. This region has no homologous analogue in any of the other TNP pro-sequences. The deletion results in a delay of six to eight hours in detection of active protease in the growth medium, as well as a 75% decrease in maximum protease production. N-terminal analysis of the mutant mature protein demonstrates that the processing site is unaltered by the pro-sequence deletion. The deletion must, therefore, modulate the kinetics of processing and/or secretion of the pro-protein. PMID- 1495389 TI - icsB: a Shigella flexneri virulence gene necessary for the lysis of protrusions during intercellular spread. AB - Shigella flexneri causes bacillary dysentery by invading epithelial cells of the colonic mucosa. We have characterized the icsB gene which is located on the virulence plasmid pWR100. After inactivation of icsB, the mutant strain remained invasive, but formed abnormally small plaques on HeLa cell monolayers, colonized only the peripheral cells of Caco-2 islets, and was unable to provoke a keratoconjunctivitis in guinea-pigs. Examination of infected HeLa cells showed that the icsB mutant was able to lyse the phagocytic vacuole and to form protrusions at the surface of infected cells, but, unlike the wild type, remained trapped in protrusions surrounded by two membranes. These results indicate that IcsB is involved in the lysis of the protrusions, a step necessary for intercellular spread. PMID- 1495390 TI - Activator-independent formation of a closed complex between sigma 54-holoenzyme and nifH and nifU promoters of Klebsiella pneumoniae. AB - The alternative sigma factor sigma 54 is required for transcription of nitrogen fixation genes in Klebsiella pneumoniae and other diazotrophs. The nif genes, and other E sigma 54-dependent genes whose products are necessary for a wide range of processes, are postively regulated. A unifying model that is well supported by studies on nif and other nitrogen-regulated (ntr) genes includes the central tenet that sigma 54 confers upon core RNA polymerase the ability to recognize and bind specific promoter sequences, but not the ability to isomerize to the open complex without assistance from the appropriate activator protein. Direct physical evidence for formation of an activator-independent complex between E sigma 54 and the NifA-dependent K. pneumoniae nifH and nifU promoters has, to date, been lacking. Using purified components we have now demonstrated formation of the closed complex at these promoters, indicating that it is an intermediate along the pathway to open complex formation. The closed complex was not detected when conserved features of the promoter were altered by mutation, nor was its stability increased when integration host factor protein was bound adjacent to the E sigma 54 recognition sequence. PMID- 1495391 TI - A Salmonella dublin virulence plasmid locus that affects bacterial growth under nutrient-limited conditions. AB - This paper reports the characterization of a new locus, vagC/vagD, on the virulence plasmid of Salmonella dublin. Strain G19, harbouring a TnA insertion in vagC, exhibited reduced virulence although vagC was outside the 8 kb essential virulence region. G19 was also unable to grow on minimal-medium containing various sole carbon/energy sources, unlike the wild-type and plasmid-cured strains. Sequencing of the locus revealed the presence of two ORFs (vagC and vagD) which overlapped by one nucleotide. The VagC polypeptide (12 kDa) was observed using minicell expression. Results indicated that vagD was responsible for the phenotypic differences observed between the wild type and G19, and that vagC modulated the activity of vagD. Furthermore, microscopic analysis of G19 cells harvested from minimal-medium plates showed that a high proportion of cells were elongated, which suggested that vagC and vagD might be involved in coordination of plasmid replication with cell division. We propose that vagD, under certain environmental conditions, acts to prevent cell division until plasmid replication is complete, thus aiding plasmid maintenance. vagC and vagD are absent from the related virulence plasmid of Salmonella typhimurium. PMID- 1495392 TI - In vivo characterization of tus gene expression in Escherichia coli. AB - The tus gene encodes a DNA-binding protein (Tus) that inhibits replication forks at specific block-sites within the terminus region of the Escherichia coli chromosome. One of these block-sites, TerB, is adjacent to the tus gene. Using primer extension and a promoter fusion to characterize in vivo expression, we have demonstrated that the tus transcription start site is within TerB, and that Tus protein autoregulates expression at this weak promoter. We have also demonstrated that a minority of tus transcripts are initiated from an upstream region that contains two additional open reading frames. This readthrough transcription into tus is reduced in the presence of Tus protein. PMID- 1495393 TI - An Aspergillus fumigatus alkaline protease mutant constructed by gene disruption is deficient in extracellular elastase activity. AB - Invasive pulmonary aspergillosis, usually caused by Aspergillus fumigatus, is a life-threatening condition of immunosuppressed patients. We have created a mutant strain of this fungus that lacks an extracellular alkaline protease (AFAlp). This was accomplished by transformation of A. fumigatus with a plasmid containing a selectable marker for hygromycin B resistance, and a 504 bp segment of the AFAlp gene, obtained by polymerase-chain-reaction-based amplification of A. fumigatus genomic DNA. Approximately 25% of transformants resulted from disruption of the AFAlp gene. SDS-polyacrylamide gel electrophoresis of proteins from the culture filtrate of a strain carrying the AFAlp gene disruption showed that it lacked a major protein of 33 kDa. Furthermore, in contrast to the culture filtrate from wild-type cells, the mutant had undetectable activity on azocollagen and elastin Congo red, over a broad pH range. This shows that AFAlp accounts for most, if not all, of the extracellular elastinolytic activity of A. fumigatus, and that the mutant strain will be useful in assessing the role of AFAlp in pathogenicity. PMID- 1495394 TI - Phylogeny of LCR-1 and OXA-5 with class A and class D beta-lactamases. AB - The nucleotide sequences of blaLCR-1 and blaOXA-5 beta-lactamase genes have been determined. Polypeptide products of 260 and 267 amino acids with estimated molecular masses of 27 120 Da and 27,387 Da were obtained for the mature form of LCR-1 and OXA-5 proteins. A progressive alignment was used to evaluate the extent of identity between LCR-1 and OXA-5 with 29 other beta-lactamase amino acid sequences. The data showed that both belong to class D. We identified amino acids conserved in 24 positions for class A beta-lactamases and in 28 positions for five class D enzymes. The structural similarities between class A and class D beta-lactamases are more extensive than indicated by earlier biochemical studies with overall 16% identity between both classes. From the alignment, dendograms were constructed with a distance-matrix and parsimony methods which defined three major groups of proteins subdivided into clusters giving insight on beta lactamase phylogeny and evolution. PMID- 1495395 TI - Memory and cognition applied. PMID- 1495396 TI - Prompt comprehension in UNIX command production. AB - We hypothesize that a cognitive analysis based on the construction-integration theory of comprehension (Kintsch, 1988) can predict what is difficult about generating complex composite commands in the UNIX operating system. We provide empirical support for assumptions of the Doane, Kintsch, and Polson (1989, 1990) construction-integration model for generating complex commands in UNIX. We asked users whose UNIX experience varied to produce complex UNIX commands, and then provided help prompts whenever the commands that they produced were erroneous. The help prompts were designed to assist subjects with respect to both the knowledge and the memory processes that our UNIX modeling efforts have suggested are lacking in less expert users. It appears that experts respond to different prompts than do novices. Expert performance is helped by the presentation of abstract information, whereas novice and intermediate performance is modified by presentation of concrete information. Second, while presentation of specific prompts helps less expert subjects, they do not provide sufficient information to obtain correct performance. Our analyses suggest that information about the ordering of commands is required to help the less expert with both knowledge and memory load problems in a manner consistent with skill acquisition theories. PMID- 1495398 TI - Memory recall in a process control system: a measure of expertise and display effectiveness. AB - Previous research has shown that memory-recall performance is correlated with domain expertise. In this study, a process control system was selected as a vehicle for conducting research on memory recall. The primary purposes of the present work were to determine if the classic expertise effects originally obtained in chess generalize to this novel domain and to evaluate the validity of memory recall as a measure of display effectiveness. Experts and novices viewed dynamic event sequences showing the behavior of a thermal-hydraulic system with two different displays, one that only contained information about the physical components in the system (P) and another that also contained information about higher order functional variables (P+F). There were three types of trials: normal, where the system was operating correctly; fault, where a single fault was introduced; and random, where the system's behavior did not obey physical laws. On each trial, subjects were asked to recall the final state of the system and to diagnose the system state. The P+F display resulted in superior diagnosis performance compared with the P display. With regard to memory, there was some evidence of an interaction between trial type and expertise, with experts outperforming novices but primarily on meaningful trials. In addition, memory for the subset of variables most critical to diagnosis was better with the P+F display than with the P display, thereby indicating that memory recall can be a sensitive measure of display effectiveness. The results also clarify a theoretical problem that has existed for some time in the literature, namely, the conditions under which expertise advantages are to be expected in memory-recall tasks. Collectively, these findings point to the potential benefits of adopting an applied context as a test bed for basic research issues. PMID- 1495397 TI - The correlation of feature identification and category judgments in diagnostic radiology. AB - Expert and novice radiologists were given films accompanied by clinical histories that supported a diagnosis either of bronchiolitis or of normal. To provide a plausible task context, some films were radiologically unambiguous and were accompanied by histories consistent with them. For a set of radiologically difficult films from confirmed normal or bronchiolitis patients, fictitious normal or abnormal histories were counterbalanced with the films. The clinical histories affected ratings both of diagnosis and of features present on the difficult films. Thus, uncertainty about individual features evidently was affected by history, and features did not act as an independent source of information. The dependence of feature calls on an overall judgment was also suggested by intra-observer agreement in another study in which an explicit diagnosis was not requested. It is unclear whether the history increased discrimination between normal and abnormal films, or indiscriminately added evidence for or against the disease. Factors are discussed that make it appropriate for feature identification to be partially dependent on category identification. PMID- 1495399 TI - Importance of the kind of cue for judgments of learning (JOL) and the delayed-JOL effect. AB - The delayed-JOL effect is the finding in which judgments of learning (JOLs) are more accurate at predicting eventual recall when they are made a short time after study rather than immediately after study. The present research replicated this effect and found that the kind of cue that is used for JOLs is critical. In particular, following the study of stimulus-response paired associates, there is an extremely robust delayed-JOL effect when the cue for JOLs is the stimulus alone (every one of 45 subjects showed the effect); however, there is little, if any, delayed-JOL effect when the cue for JOLs is the stimulus-response pair. This finding has important implications for education: To have the greatest accuracy at predicting eventual recall, a person should make JOLs not immediately after study but, instead, shortly after study (i.e., delayed JOLs) with the cue for JOLs being the stimulus alone. The theoretical mechanisms for the delayed-JOL effect are currently unknown, but some speculations are offered. PMID- 1495400 TI - The methodology of testing naive beliefs in the physics classroom. AB - Many undergraduates harbor a variety of misbeliefs about physical objects in motion--for instance, that a bomb will fall straight down when dropped from a moving airplane. The evidence that these misbeliefs are resistant to correction by college-level physics courses, however, has often been based on methodologies that lack adequate internal validity. We used a quasi-experimental "before and after" design to assess the impact of two college physics courses, and we examined selection-bias, test-retest, and task-format factors directly. Initial accuracy and significant improvements due to instruction varied considerably by problem category and subject group; thus, in several ways, the results refute the general conclusion that conventional physics instruction does little to correct students' misbeliefs. We conclude by advocating the quasi-experimental approach for studies of naive beliefs in physics as well as for other situations in which the impact of classroom instruction is of interest. PMID- 1495401 TI - Information selection and use in hypothesis testing: what is a good question, and what is a good answer? AB - The process of hypothesis testing entails both information selection (asking questions) and information use (drawing inferences from the answers to those questions). We demonstrate that although subjects may be sensitive to diagnosticity in choosing which questions to ask, they are insufficiently sensitive to the fact that different answers to the same question can have very different diagnosticities. This can lead subjects to overestimate or underestimate the information in the answers they receive. This phenomenon is demonstrated in two experiments using different kinds of inferences (category membership of individuals and composition of sampled populations). In combination with certain information-gathering tendencies, demonstrated in a third experiment, insensitivity to answer diagnosticity can contribute to a tendency toward preservation of the initial hypothesis. Results such as these illustrate the importance of viewing hypothesis-testing behavior as an interactive, multistage process that includes selecting questions, interpreting data, and drawing inferences. PMID- 1495402 TI - The role of availability in the estimation of national populations. AB - In two parallel experiments, conducted 17 months apart, we examined the relations among population estimates, availability, and media coverage of the 100 countries with populations of 4 million or more. The results were consistent with the main hypothesis, that availability influences population estimates. Specifically, we found that (1) rated knowledge of each country (our measure of availability) was strongly correlated with estimated population for that country; (2) rated knowledge was more strongly correlated with estimated population than were other plausible predictors, such as land area; (3) a strong partial correlation between rated knowledge and estimated population remained even after true population and true land area were partialed out; and (4) longitudinal changes in rated knowledge predicted longitudinal changes in estimated population. Also as hypothesized, media coverage was positively related to availability and to population estimates. Further, we found that population estimates, rated knowledge, and amount of media coverage that each country received were very stable over the year-and-a-half period. These results led us to consider when availability is most likely to be relied upon heavily in quantitative estimation and how it may be integrated with other knowledge to derive quantitative estimates. PMID- 1495403 TI - Working-memory mediation of adult age differences in integrative reasoning. AB - Three research methods were used to investigate the hypothesized mediational influence of working memory on age-related differences in integrative reasoning. Results from all three procedures were consistent with the hypothesis because (1) statistical control of an index of working memory attenuated the age differences in reasoning accuracy, (2) young adults were more accurate than older adults in a measure reflecting the preservation of information during processing, and (3) young adults performing the task with a concurrent memory load exhibited a qualitative pattern of performance similar to that of older adults performing the task without a concurrent memory load. PMID- 1495404 TI - The effect of foregrounding on readers' use of predictive inferences. AB - This research extends previous attempts to determine whether subjects make predictive inferences during comprehension. For example, when subjects read a passage about someone falling out of a 14th-story window, do they infer that the person is dead? Previous research in which lexical decision, word naming, and recognition tasks have been used for detecting predictive inferences has had mixed results. In experiment 1, a word-stem completion task was used to test for predictive inferences. The word stems were formed from target inferences that followed either priming or control passages. The data revealed that predictive inferences are generated only about concepts that are foregrounded in the passages. In Experiments 2 and 3, lexical decision and naming were used to test for predictive inferences. The lexical decision data replicated the word-stem completion data. A control experiment ruled out a simple context-checking explanation for the lexical decision results. The naming data indicated that this tasks was not sensitive to elaborative inference generation. The results show that readers make predictive inferences, but do so selectively. PMID- 1495405 TI - Caricature and face recognition. AB - Although caricatures are often gross distortions of faces, they frequently appear to be super-portraits capable of eliciting recognition better than veridical depictions. This may occur because faces are encoded as distinctive feature deviations from a prototype. The exaggeration of these deviations in a caricature may enhance recognition because it emphasizes the features of the face that are encoded. In two experiments, we tested the superportrait hypothesis and the encoding-by-caricature hypothesis. In the first experiment, caricatures were recognized better than faces, and true caricatures of previously seen faces were recognized better than the faces from which the caricatures had been developed. In the second experiment, faces and their caricatures were tachistoscopically presented in a sequential same/different reaction time task. Subjects were slower to distinguish the stimuli when the face preceded its caricature, indicating that caricatures are more similar to the encoded representation of a face than are stimuli in which the distinctive features are deemphasized. PMID- 1495407 TI - Verbal recoding of visual stimuli impairs mental image transformations. AB - Two experiments were carried out to test the hypothesis that verbal recoding of visual stimuli in short-term memory influences long-term memory encoding and impairs subsequent mental image operations. Easy and difficult-to-name stimuli were used. When rotated 90 degrees counterclockwise, each stimulus revealed a new pattern consisting of two capital letters joined together. In both experiments, subjects first learned a short series of stimuli and were then asked to rotate mental images of the stimuli in order to detect the hidden letters. In Experiment 1, articulatory suppression was used to prevent subjects from subvocal rehearsal when learning the stimuli, whereas in Experiment 2, verbal labels were presented with each stimulus during learning to encourage a reliance on the verbal code. As predicted, performance in the imagery task was significantly improved by suppression when the stimuli were easy to name (Experiment 1) but was severely disrupted by labeling when the stimuli were difficult to name (Experiment 2). We concluded that verbal recoding of stimuli in short-term memory during learning disrupts the ability to generate veridical mental images from long-term memory. PMID- 1495408 TI - The biosynthesis of phospholipids. PMID- 1495406 TI - Nonverbal priming in amnesia. AB - In this experiment, we examined whether a group of well-characterized amnesic patients would exhibit normal priming for novel nonverbal materials after a single exposure. Both amnesic patients and normal control subjects studied line figures and were then given a priming test in which they were asked to reproduce both old (studied) and new (unstudied) figures after a brief exposure. The measure of priming was the number of old patterns drawn correctly relative to the number of new patterns drawn correctly. Both subject groups reproduced more old patterns than new patterns, and the effect was similar in the two groups. In contrast, amnesic patients were significantly impaired on a recognition memory test for the items that had been presented. This study contributes to recent evidence that implicit memory can support the rapid acquisition of novel verbal and nonverbal information. Perceptual priming for such material is independent of the structures damaged in amnesia. PMID- 1495409 TI - Biosynthesis of bis(monoacylglycero)phosphate in liver and macrophage lysosomes. PMID- 1495410 TI - 2-acylglycerophosphoethanolamine acyltransferase/acyl-[acyl-carrier- protein] synthetase from Escherichia coli. PMID- 1495411 TI - Strategies for generating phospholipid synthesis mutants in yeast. PMID- 1495412 TI - Phosphatidate phosphatase from yeast mitochondria. PMID- 1495413 TI - Strategies for isolating somatic cell mutants defective in lipid biosynthesis. PMID- 1495414 TI - Serine-ethanolamine base-exchange enzyme from rat brain. PMID- 1495415 TI - Phosphatidylserine decarboxylase from Escherichia coli. PMID- 1495416 TI - Phosphatidylserine decarboxylase from rat liver. PMID- 1495417 TI - Phosphatidylethanolamine N-methyltransferase from rat liver. PMID- 1495418 TI - Alkyldihydroxyacetonephosphate synthase. PMID- 1495419 TI - Alkyldihydroxyacetonephosphate synthase from guinea pig liver peroxisomes. PMID- 1495420 TI - Plasmanylethanolamine delta 1-desaturase. PMID- 1495421 TI - 1-alkyl-2-lyso-sn-glycero-3-phosphocholine acetyltransferase. PMID- 1495422 TI - Acyl/alkyldihydroxyacetone phosphate reductase from guinea pig liver peroxisomes. PMID- 1495423 TI - Enzymes of ceramide biosynthesis. PMID- 1495424 TI - Use of N-([1-14C]hexanoyl)-D-erythro-sphingolipids to assay sphingolipid metabolism. AB - An advantage of using N-([1-14C]hexanoyl)sphingolipids to assay sphingolipid metabolism is their ability to rapidly and spontaneously transfer into biological membranes without destroying membrane integrity. This property allows analysis of the activity of enzymes of sphingolipid metabolism under conditions in which the rate of product formation is not limited by availability of substrate, as is often the case with naturally occurring lipids whose rates of spontaneous transfer are extremely slow. Thus, the use of N-([1-14C]hexanoyl)sphingolipids provides an alternative means for studying sphingolipid metabolism in vitro. PMID- 1495425 TI - UDP-N-acetylglucosamine 3-O-acyltransferase from Escherichia coli. PMID- 1495426 TI - Lipid A disaccharide synthase from Escherichia coli. PMID- 1495427 TI - 3-deoxy-D-manno-octulosonate transferase and late acyltransferases of lipopolysaccharide biosynthesis. PMID- 1495428 TI - Eukaryotic lipopolysaccharide deacylating enzyme. PMID- 1495429 TI - Transfer activity and acyl-chain specificity of phosphatidylcholine transfer protein by fluorescence assays. PMID- 1495430 TI - Phosphatidylinositol transfer proteins from higher eukaryotes. PMID- 1495431 TI - Phospholipid transfer proteins from yeast. PMID- 1495432 TI - Phospholipid transfer proteins from higher plants. PMID- 1495433 TI - Phosphatidylserine synthesis and transport to mitochondria in permeabilized animal cells. PMID- 1495434 TI - Subcellular distribution of nonspecific lipid transfer protein from rat tissues. PMID- 1495435 TI - Glycerophosphate acyltransferase from Escherichia coli. PMID- 1495436 TI - Glycerophosphate acyltransferase from liver. PMID- 1495437 TI - Strategies for generating and utilizing phospholipid synthesis mutants in Escherichia coli. PMID- 1495438 TI - Coenzyme A-independent acyltransferase. PMID- 1495439 TI - Lysophosphatidylcholine acyltransferase. PMID- 1495440 TI - 1-alkyl- and 1-alkenylglycerophosphocholine acyltransferases. PMID- 1495441 TI - Dihydroxyacetone phosphate acyltransferase. PMID- 1495442 TI - Diacylglycerol acyltransferase and monoacylglycerol acyltransferase from liver and intestine. PMID- 1495443 TI - [Defined daily dose--a suitable measure of therapy costs?]. PMID- 1495444 TI - [Non-steroidal anti-inflammatory drugs--more than prostaglandin synthesis inhibitors!]. PMID- 1495445 TI - [Therapy and prevention of migraine. Revised recommendations of the German Migraine and Headache Society]. PMID- 1495446 TI - [New bacterial resistance mechanisms]. PMID- 1495447 TI - [Interactions between calcium and fluoride?]. PMID- 1495448 TI - Bone marrow transplants for malignant diseases. PMID- 1495449 TI - [Beta-2-microglobulin in hyperthyroidism]. AB - The aims of the study were to clarify the cause of increased serum beta 2 microglobulin as a marker of thyroid hyperfunction. Serum beta 2-microglobulin was measured in 31 untreated hyperthyroid patients, all of them with normal renal function. Twenty-one subjects were affected by diffuse toxic goiter and 10 by toxic adenoma. Serum free thyroid hormones, TSH, anti-thyroglobulin and anti microsomal antigen autoantibodies were determined, too. Thyroid hormone and creatinine levels did not differed between both sets of patients. beta 2 microglobulin was higher than normal in 90% of cases with diffuse toxic goiter and in 70% of those with toxic adenoma (p less than 0.05), but mean beta 2 microglobulin concentrations didn't differ between the two groups. No difference was found in beta 2-microglobulin levels in diffuse toxic goiter group according to the presence or absence of autoantibodies. beta 2-Microglobulin and thyroid hormones were not correlated in either diffuse toxic goiter and toxic adenoma groups. These data confirm the high prevalence of elevated beta 2-microglobulin concentrations in hyperthyroidism. As renal function was normal, this rise is due to beta 2-microglobulin overproduction. This increased production is a hormone mediated effect, even if lymphocyte activation may contribute in diffuse toxic goiter. beta 2-microglobulin is not correlated with thyroid hormone concentrations so that at present it isn't a useful marker of hyperthyroidism severity for practical purposes. PMID- 1495450 TI - [Effect of treatment with biosynthetic GH on thyroid function in patients with an isolated deficiency of GH]. AB - The use of GH treatment in subjects with a GH deficiency has led to contrasting results concerning its impact to develop thyroid hyperfunction, whereas many others have underlined the possible onset of hypothyroidism. A number of studies have been carried out over short periods in subjects with multiple tropin deficiencies, in healthy adults or adults with GH deficiencies, in healthy adults or adults with GH deficiencies. The aim of the present study was to assess the effect of prolonged treatment with biosynthetic GH on thyroid function in children with an isolated idiopathic GH deficiency. The study included 8 children (mean age 10.4 +/- 0.8 years) with GH deficiencies treated with biosynthetic GH and 8 children with familial retarded stature of a similar age (mean age 10.3 +/- 0.7 years) who represented the control group. Serum levels of T3, T4, FT3, FT4 and TSH were measured at the start of the study and after one year of continuous GH treatment in subjects with GH deficiency; the same tests were performed in the control group on recruitment and after one year's observation without therapy. T4 and FT4 levels diminished, but not significantly, whereas there was a significant increase in plasma levels of T3 and FT3 (p less than 0.01); TSH values were significantly reduced in the treated group (p = 0.025). No significant variations in thyroid parameters were found in the control group. These data support the hypothesis of an increased peripheral conversion of T4 into T3 due to GH therapy; in conclusion, however, no significant variation in thyroid function was observed following GH replacement therapy, even if prolonged, in subjects with an idiopathic isolated GH deficiency. PMID- 1495452 TI - [Profile of thyroid hormones in aging: evaluation of a hospitalized elderly population]. AB - The aim of the study is to evaluate thyroid serum levels in a geriatric community to confirm the presence of a low T3 syndrome during normal ageing. The authors consider 413 subjects (125 male and 288 female) admitted to our Geriatric Division. The group affected by thyroid and extrathyroid disease (such us malnutrition, diabetes mellitus, renal failure, etc.) was withdrawn. In the selected patients (271) was operated a statistical evaluation to correlate the hormonal parameters (T3, T4, TSH, FT3, FT4) with age and sex. According to international literature, we confirm a progressive T4 and FT4 reduction (p less than 0.05) during ageing, both in male and in female. These data range within normal values. On the contrary, TSH shows no modifications with age and sex. Unlike all other parameters, T3 presents a more evident decrement with age, confirming a low T3 syndrome. PMID- 1495451 TI - [Correlation between hormonal and metabolic profiles in women with polycystic ovary syndrome]. AB - To investigate the sex hormone status of women with polycystic ovary syndrome (PCO) and to relate this to serum levels of glucose, insulin, lipids and lipoproteins, 90 women with PCO (30 obese: BMI greater than 30 kg/m2; 30 overweight: BMI greater than 25- less than 30 kg/m2; 30 non obese: BMI less than 25 kg/m2) and 60 normal ovulatory women (20 obese; 20 overweight; 20 non obese) were studied. The women with PCO had significantly increased LH, FSH and androgen levels and significantly decreased SHBG levels compared to the normal women. Obese women with PCO had higher concentrations of fasting glucose, fasting insulin, incremental glucose area, incremental insulin area and lipid than overweight and non obese women with PCO and overweight and non obese control subjects, but were similar in obese normal women. There were decreases in high density lipoproteins levels in both the obese groups (obese PCO and obese control women). Lipid and lipoprotein concentrations did not differ in the obese, overweight and non obese PCO women compared to the normal groups while HDL cholesterol were decreased in obese PCO and obese control women. The correlations between hormone, glucose, insulin, lipid and lipoprotein levels were different among the six groups. Non obese PCO women had: inverse correlations between free testosterone and incremental glucose area (r = -0.5128, P = 0.03); positive correlations between SHBG and alpha-lipoproteins (r = 0.9159, P = 0.001). Non obese normal women had: positive correlations between fasting insulin and total testosterone (r = 0.5272, P = 0.043) and between SHBG and beta-lipoproteins (r = 0.7445, P = 0.014) and LDL cholesterol (r = 0.7360, P = 0.010).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1495453 TI - [Clinical evaluation of desmopressin (DDAVP) in diabetes insipidus: solution vs tablets]. AB - Efficacy and tolerability of perorally administered desmopressin were evaluated in 12 adult patients suffering from central diabetes insipidus. According to the results of the study desmopressin should be administered at a higher dosage than 300 micrograms/die to obtain the same antidiuretic effect as with the intranasal administration. No significant changes in body weight, arterial pressure and blood chemistry parameters have been detected over the whole administration period and only some slight side-effects occurred. Oral desmopressin may be considered as an effective alternative to traditional intranasal administration and it may significantly improve patients' compliance. PMID- 1495454 TI - [Effect of octreotide on blood glucose levels in poorly compensated insulin dependent diabetics on insulin treatment]. AB - The metabolic effects of a long-acting somatostatin analogue, octreotide, in type I diabetic patients on conventional insulin therapy have been evaluated. Octreotide has been administered by subcutaneous continuous infusion employing a minipump; in 10 patients the infusion was performed from 08.00 a.m. to 08.00 p.m. and in 7 patients from 08.00 p.m. to 08.00 a.m. In both groups the drug dose was 50 mcg/12h and before starting the infusion an additional dose of 12.5 mg was rapidly injected s.c. In a third group of 8 patients octreotide was administered at a dosage of 50 mcg by subcutaneous injections at 07.00 a.m.; 3.00 p.m.; 11.00 p.m. A significant reduction of glucose levels was obtained in all patients and the results observed by minipump or by multiple injections were superimposable. It is to note that the daily drug dose employed by minipump was smaller. The evaluation of octreotide usefulness, in addition to conventional insulin therapy, in the management of type I diabetic patients, needs further extensive studies. PMID- 1495455 TI - Medical school of the '90s. Opening doors to diversity, opportunity. PMID- 1495456 TI - Nurtured toward excellence. Medical school grads reflect on their training. PMID- 1495457 TI - The politics of HealthRight. Piecing it together. PMID- 1495458 TI - A physician's ethical and legal obligations to treat HIV-infected patients. The MMA Committee on Ethics and Medical-Legal Affairs. PMID- 1495459 TI - HealthRight's mandate for change. PMID- 1495460 TI - The Medicare/Medicaid anti-kickback provisions. Enforcement implications of the Hanlester network decisions. PMID- 1495461 TI - DDI more effective than AZT. PMID- 1495462 TI - State passes AIDS reporting bill. PMID- 1495463 TI - CLIA should classify WBC count as 'waived'. PMID- 1495464 TI - Chylothorax in the neonate: a case study. PMID- 1495465 TI - Detecting and preventing infant hearing loss. PMID- 1495466 TI - The critical path: an evaluation of the applicability of nursing case management in the NICU. PMID- 1495467 TI - Notes from work in Poland with a perinatal education program. PMID- 1495468 TI - Transition from hospital to home. Part II. PMID- 1495469 TI - Pulmonary interstitial emphysema: a review. PMID- 1495471 TI - Sampling neonatal populations. PMID- 1495470 TI - Introduction to the neonatal radiology column. PMID- 1495472 TI - Missouri State Medical Association. 1992-1993 membership directory. PMID- 1495474 TI - Characterization of the Aspergillus niger pelB gene: structure and regulation of expression. AB - The nucleotide sequence of pelB, a member of the Aspergillus niger pectin lyase multigene family, has been determined. The pelB gene product, PLB, shares 65% amino acid identity with pectin lyase A (PLA) and 60% with pectin lyase D (PLD). Although growth of pelB multicopy transformants on pectin-containing media results in elevated pelB mRNA levels, pectin lyase B (PLB) is barely detectable. This is probably due to degradation of PLB by acid proteases, since multicopy transformants grown on pectin medium with a high concentration of phosphate, leading to a less rapid decline in pH, secrete detectable amounts of PLB. To produce PLB in high amounts under conditions where few other extracellular enzymes are present, we tried two strategies. Firstly, heterologous expression of the pelB gene in A. nidulans, and secondly, expression of the pelB gene under control of the constitutive A. niger pki promoter. PMID- 1495473 TI - Gene conversion in the Escherichia coli RecF pathway: a successive half crossing over model. AB - Gene conversion--apparently non-reciprocal transfer of sequence information between homologous DNA sequences--has been reported in various organisms. Frequent association of gene conversion with reciprocal exchange (crossing-over) of the flanking sequences in meiosis has formed the basis of the current view that gene conversion reflects events at the site of interaction during homologous recombination. In order to analyze mechanisms of gene conversion and homologous recombination in an Escherichia coli strain with an active RecF pathway (recBC sbcBC), we first established in cells of this strain a plasmid carrying two mutant neo genes, each deleted for a different gene segment, in inverted orientation. We then selected kanamycin-resistant plasmids that had reconstituted an intact neo+ gene by homologous recombination. We found that all the neo+ plasmids from these clones belonged to the gene-conversion type in the sense that they carried one neo+ gene and retained one of the mutant neo genes. This apparent gene conversion was, however, only very rarely accompanied by apparent crossing-over of the flanking sequences. This is in contrast to the case in a rec+ strain or in a strain with an active RecE pathway (recBC sbcA). Our further analyses, especially comparisons with apparent gene conversion in the rec+ strain, led us to propose a mechanism for this biased gene conversion. This "successive half crossing-over model" proposes that the elementary recombinational process is half crossing-over in the sense that it generates only one recombinant DNA duplex molecule, and leaves one or two free end(s), out of two parental DNA duplexes. The resulting free end is, the model assumes, recombinogenic and frequently engages in a second round of half crossing-over with the recombinant duplex. The products resulting from such interaction involving two molecules of the plasmid would be classified as belonging to the gene-conversion type without crossing-over. We constructed a dimeric molecule that mimics the intermediate form hypothesized in this model and introduced it into cells. Biased gene conversion products were obtained in this reconstruction experiment. The half crossing-over mechanism can also explain formation of huge linear multimers of bacterial plasmids, the nature of transcribable recombination products in bacterial conjugation, chromosomal gene conversion not accompanied by flanking exchange (like that in yeast mating-type switching), and antigenic variation in microorganisms. PMID- 1495475 TI - Genetic structure, isolation and characterization of a Bacillus licheniformis cell wall hydrolase. AB - A DNA fragment containing the gene for a cell wall hydrolase of Bacillus licheniformis was cloned into Escherichia coli. Sequencing of the fragment showed the presence of an open reading frame which encodes a polypeptide of 253 amino acids with a molecular mass of 27,513. The gene was designated as cwlM, for cell wall lysis. The deduced amino acid sequence indicated that there is a repeated sequence consisting of 33 amino acid residues in the C-terminal region. Deletion of the C-terminal region did not lead to any loss of cell wall lytic activity. The gene product purified from E. coli cells harboring a cwlM-bearing plasmid exhibited a M(r) value of 29 kDa on SDS-polyacrylamide gels, and characterization of the specific substrate bond cleaved by CWLM indicated that the enzyme is an N acetylmuramoyl-L-alanine amidase (EC 3.5.1.28). The enzyme hydrolyzed the cell wall of Micrococcus luteus more efficiently than those of B. licheniformis and B. subtilis, but the truncated CWLM (lacking the C-terminal region) had lost this preference. CWLM prepared from B. subtilis cells harboring a plasmid containing cwlM had a similar M(r) value to that from E. coli. Amino acid sequence homologies between CWLM and other amidases, and their protein structures are discussed. PMID- 1495476 TI - Regulatory sequences for expressing genes in oomycete fungi. AB - Promoter and terminator sequences from a range of species were tested for activity in the oomycetes, a group of lower fungi that bear an uncertain taxonomic affinity to other organisms and in which little is known of the sequences required for transcription. Transient assays, using the reporter gene beta-glucuronidase (GUS), were used to examine the function of these promoters and terminators in the plant pathogens Phytophthora infestans and P. megasperma f. sp. glycinea, and in the saprophytic water mold, Achlya ambisexualis. Oomycete promoters, isolated from the ham34 and hsp70 genes of Bremia lactucae and the actin gene of P. megasperma f. sp. glycinea, resulted in high levels of GUS accumulation in each of the three oomycetes. In contrast, little or no activity was detected when promoters from higher fungi (four ascomycetes and one basidiomycete), plants, and animals were tested. The terminator from the ham34 gene resulted in much higher levels of GUS accumulation than did others, although an oomycete terminator was not absolutely required for expression. Transcript mapping of RNA from stable transformants confirmed accurate initiation from the B. lactucae hsp70 promoter and termination within 3' ham34 sequences in P. infestans. Our results indicate that the transcriptional machinery of the oomycetes differs significantly from that of the higher fungi, but that enough conservation exists within the class to allow vectors developed from one oomycete species to be used for others. PMID- 1495477 TI - Cloning and nucleotide sequence determination of twelve mutant dnaA genes of Escherichia coli. AB - Plasmids carrying different regions of the wild-type dnaA gene were used for marker rescue analysis of the temperature sensitivity of twelve strains carrying dnaA mutations. The different dnaA(Ts) mutations could be unambiguously located within specific regions of the dnaA gene. The mutant dnaA genes were cloned on pBR322-derived plasmids and on nucleotide sequencing by dideoxy chain termination the respective mutations were determined using M13 clones carrying the relevant parts of the mutant dnaA gene. Several of the mutant dnaA genes were found to have two mutations. The dnaA5, dnaA46, dnaA601, dnaA602, dnaA604, and dnaA606 genes all had identical mutations corresponding to an amino acid change from alanine to valine at amino acid 184 in the DnaA protein, close to the proposed ATP binding site, but all carried one further mutation giving rise to an amino acid substitution. The dnaA508 gene also had two mutations, whereas dnaA167, dnaA203, dnaA204, dnaA205, and dnaA211 each had only one. The pairs dnaA601/602, dnaA604/606, and dnaA203/204 were each found to have identical mutations. Plasmids carrying the different dnaA mutant genes intact were introduced into the respective dnaA mutant strains. Surprisingly, these homopolyploid mutant strains were found to be temperature resistant in most cases, indicating that a high intracellular concentration of the mutant DnaA protein can compensate for the decreased activity of the protein. PMID- 1495478 TI - New tools for mitochondrial genetics of Chlamydomonas reinhardtii: manganese mutagenesis and cytoduction. AB - A novel and efficient genetic procedure is described for generating mitochondrial mutants of the green alga Chlamydomonas reinhardtii. The development of a mutagenesis procedure using manganese cations and the application of cytoduction techniques resulted in a combined approach for the generation and analysis of mitochondrial mutants. Although mitochondrial mutations are inherited in sexual crosses from the minus mating type parent, the cytoduction technique can be used to transfer mitochondrial mutations into recipient strains with different genetic backgrounds, irrespective of their mating type. Cytoduction allows the transfer of mitochondrial markers from diploid to haploid cells also, which is of great benefit since diploid cells do not germinate in C. reinhardtii. We report here the isolation and characterisation of eight mutants, which are resistant to the antibiotics myxothiazol and mucidin. The mutants all have point mutations in the mitochondrial gene for apocytochrome b. Using in vitro-amplified cytb gene fragments as probes for direct DNA sequencing, three different types of single base pair substitutions were revealed in all mutants tested. In particular, amino acid substitutions in the mutant apocytochrome b polypeptide have been identified at residues 129, 132 and 137, which have been implicated in forming part of an antibiotic-binding niche. The amino acid substitution at position 132 has not been so far described for mutant apocytochrome b in any other organism, prokaryotic or eukaryotic. The genetic approach presented here confirms C. reinhardtii as a model system that is unique among plant cells. PMID- 1495479 TI - A topological model for the haemolysin translocator protein HlyD. AB - A topological model for HlyD is proposed that is based on results obtained with gene fusions of lacZ and phoA to hlyD. Active HlyD-LacZ fusion proteins were only generated when lacZ was fused to hlyD within the first 180 bp (60 amino acids). HlyD-PhoA proteins exhibiting alkaline phosphatase (AP) activity were obtained when phoA was inserted into hlyD between nucleotides 262 (behind amino acid position 87) and 1405 (behind amino acid position 468, only 10 amino acids away from the C-terminus of HlyD). Active insertions of phoA into the middle region of hlyD were not observed on in vivo transposition but such fusions exhibiting AP activity could be constructed by in vitro techniques. A fusion protein that carried the PhoA part close to the C-terminal end of HlyD proved to be the most stable HlyD-PhoA fusion protein. In contrast to the other, rather unstable, HlyD PhoA+ fusions, no proteolytic degradation product of this HlyD-PhoA protein was observed and nearly all the alkaline phosphatase activity was membrane bound. Protease accessibility and cell fractionation experiments indicated that the alkaline phosphatase moiety of this fusion protein was located in the periplasm as for all other HlyD-PhoA+ proteins. These data and computer-assisted predictions suggest a topological model for HlyD with the N-terminal 60 amino acids located in the cytoplasm, a single transmembrane segment from amino acids 60 to 80 and a large periplasmic region extending from amino acid 80 to the C terminus.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1495480 TI - NPK1, a nonessential protein kinase gene in Saccharomyces cerevisiae with similarity to Aspergillus nidulans nimA. AB - A new protein kinase gene [called NPK1 (for nonessential protein kinase)] has been found on chromosome I of Saccharomyces cerevisiae between CDC15 and ADE1. The 435 amino acid/48 kDa gene product is very similar to known protein kinases. It is most closely related to the nimA protein of Aspergillus nidulans, displaying 45.9% identity and 63.5% similarity in the protein kinase domain. A 1.4 kb transcript of the NPK1 gene was detected. Disruption of the NPK1 gene impedes neither growth on glucose or a variety of other carbon sources, nor mating or sporulation. PMID- 1495481 TI - The role of promoter elements of a ribosomal protein gene in Saccharomyces cerevisiae under various physiological conditions. AB - Previous work in our laboratory has shown that the 5' nontranscribed promoter region of the gene for ribosomal protein (rp) S16A-1 of Saccharomyces cerevisiae, when fused to a lacZ gene, is necessary and sufficient to cause an increase in expression of the heterologous lacZ gene fusion product after cells have been shifted from a glycerol to glucose carbon source. This increase in expression is characteristic of that observed with the native rp gene. We have sought to define more precisely those areas of the promoter that may be involved in the differential expression/regulation of RPS16A-1 when host cells are subjected to a variety of nutritional environments. It has already been demonstrated by others that the promoter regions of most rp genes contain at least one consensus element, designated UASrpg, which is necessary for the transcriptional activation and maintenance of expression of the gene during steady-state growth in rich media. Our main experimental approach has been to create a series of 5' end deletions in the promoter region of RPS16A-1. The individual truncated promoter fragments were then ligated to a lacZ fusion reporter construct. By assaying the cells for production of beta-galactosidase and determining the abundance of lacZ mRNA, we have been able to determined the extent of fusion product expression. We assayed cells under three physiological conditions: steady-state growth in glucose, steady-state growth in glycerol and during sporulation. We report four main findings of our work. PMID- 1495482 TI - Structure of the genes encoding Hordeum vulgare (1----3,1----4)-beta-glucanase isoenzymes I and II and functional analysis of their promoters in barley aleurone protoplasts. AB - Barley (1----3,1----4)-beta-glucanase isoenzyme II is synthesized in the aleurone cells during germination and secreted into the endosperm for hydrolysis of the cell walls. Its synthesis is stimulated by gibberellic acid (GA3) and repressed by abscisic acid. The gene for isoenzyme I is expressed in the aleurone, scutellum and prominently in young leaves. Close functional relatedness between the two enzymes is attested by 92% identity at the level of the amino acid sequence. The structural genes for the two enzymes each contain a large intron of 2505 bp and 2952 bp, respectively, in the codon for amino acid 25 of the 28 residue signal peptide. During evolution, homologous regions of the two introns have changed position and orientation. Furthermore, a large palindromic sequence of 327 bp in the 5' end of the intron is present only in the gene for isoenzyme II. In transient expression assays using barley aleurone protoplasts and chloramphenicol acetyl transferase as reporter the promoter of the isoenzyme I gene showed no response to GA3. However, removal of a unique 151 bp region extending from positions -402 to -552 upstream of the TATA box permitted low levels of GA3-induced expression of the reporter gene, suggesting a silencer function for this domain. High levels of GA3-responsive expression were obtained in aleurone protoplasts using the promoter of the gene encoding isoenzyme II. Truncation of this promoter revealed that sequences located within 253 bp upstream from the TATA box are sufficient to direct GA3-stimulated expression. Using the homologous barley aleurone protoplast transfection assay, it was possible to reproduce the in vivo expression characteristics of the genes for the barley (1----3,1----4)-beta-glucanase isoenzymes I and II with reporter gene constructs. PMID- 1495483 TI - A molecular marker to select for freezing tolerance in Gramineae. AB - We isolated, and expressed in Escherichia coli, a gene (Wcs120) that is strongly induced during cold acclimation of wheat. The gene product was purified and used to produce antibodies. Immunoblotting experiments with the anti-WCS120 antibody identified several cold-induced proteins named FTMs for Freezing Tolerance Markers since they are associated with the development of freezing tolerance. This protein family was found to be coordinately regulated specifically by low temperature, highly hydrophilic, stable to boiling, and to have a pI above 6.5. The accumulation kinetics during the acclimation period indicated a positive correlation with the capacity of each genotype to develop freezing tolerance. Accumulation of the proteins was higher in the freezing-tolerant genotype than in the less tolerant one. In addition, their accumulation was more pronounced in the crown and leaf tissues compared with roots, confirming a relationship to the capacity of the different tissues to develop freezing tolerance. Analysis of different species (eight monocots and four dicots) indicated that this protein family is specific for freezing-tolerant cereals. The antibody did not cross react with any of the non-cereal species examined. The anti-FTMs antibody represents a potential tool for breeders to select for freezing tolerance traits in the Gramineae. PMID- 1495484 TI - Directed excision of a transgene from the plant genome. AB - The effectiveness of loxP-Cre directed excision of a transgene was examined using phenotypic and molecular analyses. Two methods of combining the elements of this system, re-transformation and cross pollination, were found to produce different degrees of excision in the resulting plants. Two linked traits, beta glucuronidase (GUS) and a gene encoding sulfonylurea-resistant acetolactate synthase (ALSr), were integrated into the genome of tobacco and Arabidopsis. The ALSr gene, bounded by loxP sites, was used as the selectable marker for transformation. The directed loss of the ALSr gene through Cre-mediated excision was demonstrated by the loss of resistance to sulfonylurea herbicides and by Southern blot analysis. The beta-glucuronidase gene remained active. The excision efficiency varied in F1 progeny of different lox and Cre parents and was correlated with the Cre parent. Many of the lox x Cre F1 progeny were chimeric and some F2 progeny retained resistance to sulfonylureas. Re-transformation of lox/ALS/lox/GUS tobacco plants with cre led to much higher efficiency of excision. Lines of tobacco transformants carrying the GUS gene but producing only sulfonylurea-sensitive progeny were obtained using both approaches for introducing cre. Similarly, Arabidopsis lines with GUS activity but no sulfonylurea resistance were generated using cross pollinations. PMID- 1495485 TI - Individual variability in the translational regulation of ribosomal protein synthesis in Xenopus laevis. AB - Ribosomal protein synthesis is regulated by controlling the fraction of mRNA associated with polysomes. It is known that this value changes in different developmental stages during Xenopus embryogenesis or, more generally, with changing cell growth conditions. We present here an analysis of the proportion of mRNA loaded on polysomes, carried out with probes for five different ribosomal proteins on several batches of Xenopus embryos obtained from different individuals. The results obtained indicate the existence of probe-dependent and individual differences, which reflect genetic variations in the cis- and trans acting regulatory elements responsible for translational regulation. The fraction of ribosomal protein mRNA loaded onto polysomes can be used as an index of an individual's capacity for ribosome production. PMID- 1495486 TI - Recombinant repair of diverged DNAs: a study of homoeologous chromosomes and mammalian YACs in yeast. AB - Recombinational repair is the means by which DNA double-strand breaks (DSBs) are repaired in yeast. DNA divergence between chromosomes was shown previously to inhibit repair in diploid G1 cells, resulting in chromosome loss at low nonlethal doses of ionizing radiation. Furthermore, 15-20% divergence prevents meiotic recombination between individual pairs of Saccharomyces cerevisiae and S. carlsbergensis chromosomes in an otherwise S. cerevisiae background. Based on analysis of the efficiency of DSB-induced chromosome loss and direct genetic detection of intragenic recombination, we conclude that limited DSB recombinational repair can occur between homoeologous chromosomes. There is no difference in loss between a repair-proficient Pms+ strain and a mismatch repair mutant, pms1. Since DSB recombinational repair is tolerant of diverged DNAs, this type of repair could lead to novel genes and altered chromosomes. The sensitivity to DSB-induced loss of 11 individual yeast artificial chromosomes (YACs) containing mouse or human (chromosome 21 or HeLa) DNA was determined. Recombinational repair between a pair of homologous HeLa YACs appears as efficient as that between homologous yeast chromosomes in that there is no loss at low radiation doses. Single YACs exhibited considerable variation in response, although the response for individual YACs was highly reproducible. Based on the results with the yeast homoeologous chromosomes, we propose that the potential exists for intra- YAC recombinational repair between diverged repeat DNA and that the extent of repair is dependent upon the amount of repeat DNA and the degree of divergence. The sensitivity of YACs containing mammalian DNA to ionizing radiation-induced loss may thus be an indicator of the extent of repeat DNA. PMID- 1495487 TI - Cloning and sequencing of the melB gene encoding the melibiose permease of Salmonella typhimurium LT2. AB - The nucleotide sequence of the melB gene coding for the Na+ (Li+)/melibiose symporter of Salmonella typhimurium LT2 was determined, and its amino acid sequence was deduced. It consists of 1428 bp, corresponding to a protein of 476 amino acid residues (calculated molecular weight 52,800). The amino acid sequence is homologous to that of the melibiose permease of Escherichia coli K12, with 85% identical residues. All, except one, of the amino acid residues that have been reported to be important for cation or substrate recognition in the melibiose permease of E. coli are conserved in the melibiose permease of S. typhimurium. In addition, part of the sequence resembles the lactose permease of Streptococcus thermophilus, the animal glucose transporter (GLUT1), the plasmid-coded raffinose permease (RafB), and the NADH-ubiquinone oxidoreductase chain 4 (Nuo4) of Aspergillus amstelodami. PMID- 1495488 TI - Expression of pehA-bla gene fusions in Erwinia carotovora subsp. carotovora and isolation of regulatory mutants affecting polygalacturonase production. AB - In vitro gene fusions were constructed between the polygalacturonase-encoding pehA gene of the Erwinia carotovora subsp. carotovora (Ecc) strain SCC3193 and the bla gene of pBR322. The gene fusions obtained (75-2, 75-5 and 75-6) encoded hybrid proteins with the entire signal peptide and 70, 260 or 327 amino acids (aa) of the mature 376 aa PehA protein, respectively, fused to the mature part of the periplasmic beta-lactamase. All three hybrid proteins remained cell-bound in Ecc. High-level expression of the longer fusions 75-5 and 75-6 in Ecc led to reduced growth and viability of the cells. This phenotype was utilized to select for spontaneous extragenic mutations restoring normal cell growth. Two classes of regulatory mutants were obtained by this selection. First, mutants impaired in the production of several exoenzymes, including polygalacturonase, were found. These were phenotypically similar to the previously characterized Exp- mutants. Secondly, mutants specifically impaired in the production of polygalacturonase (designated PehR-), but producing and secreting wild-type levels of pectate lyase and cellulase, were obtained. The PehR- mutations were shown to affect transcriptional activation of the pehA gene. Furthermore, the PehR- as well as PehA- mutants exhibited a reduced virulence phenotype suggesting that polygalacturonase is a virulence factor in Ecc. PMID- 1495489 TI - A flower-specific cDNA encoding a novel thionin in tobacco. AB - We isolated a flower-specific cDNA, FST (flower-specific thionin), which encodes a novel thionin from tobacco. Thionins are basic and cysteine (Cys)-rich, low molecular weight proteins found in many plants. They are believed to play a role in plant defense against pathogens. The central domain of the FST protein shares homology with three gamma-thionins. Like other thionin precursors, the FST protein has an N-terminal domain characteristic of a signal peptide and an acidic C-terminal domain. FST mRNA accumulates specifically in developing flowers and its level drops as flowers mature. Transcripts are present in petals, stamens and pistil but are not detectable in sepals. In situ hybridization revealed that FST mRNA is most abundant in the epidermal cells along the adaxial surface of petals, and in the surface cell layers of the carpel and anther walls. If the FST protein indeed has a protective role in flowers, this pattern of spatial distribution of FST mRNA would appear to maximize this effect on the two internal reproductive whorls. A possible biological role for FST is discussed. PMID- 1495490 TI - Expression of the gene encoding the PR-like protein PRms in germinating maize embryos. AB - The PRms protein is a pathogenesis-related (PR)-like protein whose mRNA accumulates during germination of maize seeds. Expression of the PRms gene is induced after infection of maize seeds with the fungus Fusarium moniliforme. To further our investigations on the expression of the PRms gene we examined the accumulation of PRms mRNA in different tissues of maize seedlings infected with F. moniliforme and studied the effect of fungal elicitors, the mycotoxin moniliformin, the hormone gibberellic acid, and specific chemical agents. Our results indicate that fungal infection, and treatment either with fungal elicitors or with moniliformin, a mycotoxin produced by F. moniliforme, increase the steady-state level of PRms mRNA. PRms mRNA accumulation is also stimulated by the application of the hormone gibberellic acid or by treatment with silver nitrate, whereas acetylsalicylic acid has no effect. In situ RNA hybridization in isolated germinating embryo sections demonstrates that the PRms gene is expressed in the scutellum, particularly in a group of inner cells, and in the epithelium lying at the interface of the scutellum and the endosperm. The pattern of expression of the PRms gene closely resembles that found for hydrolytic enzymes, being confined to the scutellum and the aleurone layer of the germinating maize seed. Our results suggest that the PRms protein has a function during the normal process of seed germination that has become adapted to serve among the defence mechanisms induced in response to pathogens during maize seed germination. PMID- 1495491 TI - Structural requirements for high affinity ligand binding by estrogen receptors: a comparative analysis of truncated and full length estrogen receptors expressed in bacteria, yeast, and mammalian cells. AB - In order to better understand the structural requirements for effective high affinity binding of estrogens and antiestrogens by the human estrogen receptor (ER), a comparative study was undertaken in which we examined: 1) native ER from the MCF-7 ER-positive human breast cancer cell line; 2) full length ER expressed in yeast; 3) the ER hormone binding domain (amino acid residues 302-595) expressed in yeast; 4) a bacterially expressed protein A fusion product encoding a truncated ER (amino acid residues 240-595); and 5) a synthetic peptide encompassing amino acids 510-551 of the ER. The binding parameters studied included affinity, kinetics, structural specificity for ligands, and stability. Full length ER expressed in yeast was very similar to the MCF-7 ER in its affinity [dissociation constant (Kd), 0.35 +/- 0.05 nM], dissociation rate (t1/2, 3-4 h at 25 C), and structural specificity for both reversible and covalently attaching affinity ligands. While the truncated ER expressed in yeast was similar to MCF-7 ER in its specificity of ligand binding, it showed a slightly reduced affinity for estradiol (Kd, 1.00 +/- 0.17 nM). The bacterially expressed ER also had a lower affinity for estradiol (Kd, 1.49 +/- 0.16 nM), which may be due in part to an increase in the dissociation rate (t1/2, 0.5 h at 25 C). The attachment of covalent affinity ligands and structural specificity for a variety of reversible ligands was comparable in the bacterially expressed ER to that observed for the receptors expressed in MCF-7 cells and yeast.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1495492 TI - Structure of a receptor-binding fragment from human luteinizing hormone beta subunit determined by [1H]- and [15N]nuclear magnetic resonance spectroscopy. AB - The structure of the glycoprotein hormones (LH, CG, FSH, and TSH) and their mechanism of receptor recognition are problems of long-standing interest and speculation. Here we describe the two-dimensional [1H]nuclear magnetic resonance ([1H]NMR) analysis of a linear peptide model for the intercysteine sequence (38 57) from the beta-subunit of human (h) LH. This sequence contains functional determinants for receptor binding and postreceptor activation and is predicted by computer-based modeling to fold as a compact minidomain containing a central amphipathic helix. To test this prediction, an Arg-extended disulfide-free (38 57) analog of enhanced solubility was prepared for complementary circular dichroic and two-dimensional NMR studies. The linear peptide retains ovarian membrane receptor-binding activity. Although the peptide is not highly structured in aqueous solution, circular-dichroic analysis shows partial alpha-helix formation in a lipophilic medium (50% trifluoroethanol). Complete sequential assignment is obtained in 50% trifluoroethanol based on homonuclear and [15N]edited heteronuclear NMR methods. alpha-Helix-related (i,i + 3) connectivities are observed by nuclear-Overhauser effect spectroscopy that define an amphipathic alpha-helical segment (residues 41-48). Additional long range nuclear-Overhauser effects are observed in the C-terminal region that are consistent with beta-turns involving one or more proline residues; these may serve to reverse the direction of the peptide chain. A nuclear-Overhauser effect contact is identified between residues 38 and 55 at opposite ends of the linear sequence, suggesting that a loop configuration is significantly populated in this solvent system. These results, taken together, characterize elements of ordered structure in the 38-57 peptide, which appear to be distinguishing features of hLH (and the homologous region of hCG). We propose that the structure of this peptide provides a model for the structure of the corresponding region of native hLH in the hormone-receptor complex. PMID- 1495493 TI - Identification of the thyroid hormone-responsive messenger RNA spot 11 as apolipoprotein-A1 messenger RNA and effects of the hormone on the promoter. AB - The induction of rat hepatic mRNA S11 by L-T3 (T3) is a useful model for studying the mechanisms of thyroid hormone action. Although numerous reports have examined the response of mRNA S11 to various physiological and hormonal manipulations, the role of S11 protein in cellular metabolism remains unknown. In this study we show that mRNA S11 is abundantly expressed and regulated by T3 only in liver and small intestine. High levels of the mRNA are present at birth, but drop sharply between 30-60 days of age. These and other features of the S11 gene product were similar to those of rat apolipoprotein-A1 (Apo-A1). The sequence of S11 cDNA was identical to a portion of the Apo-A1 mRNA, thus confirming identity of the S11 mRNA. To examine whether DNA sequences immediately adjacent to the transcription start site mediate the effects of thyroid hormone, we measured the activity of an Apo-A1 gene fragment, U-1 (-474 to -7) using a transient transfection assay. The activity of the full-length U-1 DNA in HuH-7 hepatoma cells was 2- to 2.5-fold higher in the presence of thyroid hormone. This finding closely matched previous results using the in vitro nuclear run-on assay. Internal deletion of a motif that resembles a thyroid hormone response element from U-1 DNA not only abolished the induction by T3, but suppressed promoter activity by 3- to 4-fold in response to the hormone.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1495494 TI - Glucocorticoid regulation of c-myc promoter utilization in P1798 T-lymphoma cells. AB - Glucocorticoids rapidly inhibit the expression of c-myc mRNA in P1798 lymphoma cells. Statistically significant decreases can be observed within 5-10 min after the addition of glucocorticoids. Although transcription of c-myc decreases within a few hours after dexamethasone is added to P1798 cell cultures, nuclear run-on transcription cannot be used to demonstrate that the very early changes in mRNA abundance reflect corresponding changes in transcriptional activity. An RNase protection assay has been used to measure the abundance and rates of turnover of the two major c-myc transcripts arising from the P1 and P2 initiation sites. The relative rates of synthesis of the c-myc mRNAs (i.e. transcription) can be calculated from such data. The abundance of the P2 transcript exceeds that of P1 mRNA by 3- to 4-fold in midlog phase cells. The turnover rates of the two c-myc mRNAs are essentially identical (0.02 min-1), indicating that the P2 promoter is 3-4 times stronger than P1. This was confirmed by measuring the relative transcriptional activities of templates containing the individual c-myc promoters in P1798 extracts in vitro. The expression of P1 and P2 mRNAs decreases at different rates in glucocorticoid-treated cells. A 50% decrease in the abundance of P1 mRNA occurs within 1 h after the addition of dexamethasone. Expression of P2 mRNA is reduced by 50% within 4 h. However, the turnover rates of the major c myc transcripts do not change in glucocorticoid-treated cells. The t1/2 values of P1 and P2 mRNAs are about 25-30 min and not different from the turnover rates measured in control cells.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1495495 TI - Apolipoprotein-E messenger RNA in rat ovary is expressed in theca and interstitial cells and presumptive macrophage, but not in granulosa cells. AB - Apolipoprotein-E (apoE) is a constituent of various lipoproteins and is a ligand for cellular lipoprotein receptors. Unlike most apolipoproteins, apoE is synthesized in peripheral tissues, including those engaged in steroidogenesis. ApoE expression in adrenal cells inhibits cholesterol utilization for steroid synthesis and blocks signal transduction via the protein kinase-A pathway. In cultured ovarian thecal/interstitial cells, exogenous apoE has been shown to inhibit LH-induced androgen synthesis. These findings support a role for apoE as an autocrine or paracrine factor involved in regulating steroidogenesis. In the present study in situ hybridization was used to identify cell types that express apoE mRNA in ovaries from rats with a 4-day estrous cycle, from pregnant rats, from immature rats treated with PMSG to stimulate follicular development, and from PMSG-treated rats that were subsequently administered hCG to stimulate ovulation and luteinization. ApoE mRNA was localized to theca and interstitial cells of follicles in animals at all stages of the estrous cycle as well as in immature rats treated with PMSG. ApoE mRNA was not detected in oocytes, cumulus cells, or granulosa cells. High levels of apoE mRNA also were expressed by localized clusters of presumptive macrophages in atretic follicles and degenerating corpora lutea. This complex pattern of expression may indicate that apoE has multiple functions in the rat ovary. ApoE made by theca and interstitial cells may act locally as an autocrine factor to regulate androgen production. ApoE made in atretic follicles and regressing corpora lutea may serve to facilitate local transport and reutilization of lipid released as these structures degenerate. PMID- 1495496 TI - Molecular characterization of the human immunoglobulin V lambda I germline gene repertoire. AB - To advance our understanding of the human immunoglobulin V lambda germline gene contribution to normal as well as autoimmune responses, we have isolated and sequenced six germline genes of the V lambda I subgroup. These genes can be divided into three sub-subgroups on the basis of greater than or equal to 93% nucleotide sequence homology and greater than or equal to 88% deduced amino acid sequence similarity. Examination of all cDNA and protein sequences available for expressed V lambda I genes supports the assignment of these three sub-subgroups. Sequence comparisons also suggest that germline gene members of two of these sub subgroups, I-a and I-b, are preferentially utilized in the expressed V lambda I repertoire. This finding may be at least partially attributable to regulatory sequence abnormalities apparent in two of the other V lambda I germline genes (Humlv101 and Humlv104) which may interfere with their expression. PMID- 1495497 TI - New cyclosporin A analogue: synthesis and immunosuppressive activity. AB - A synthetic analogue of cyclosporine A, in which an unusual amino acid (4R)-N methyl-4-butenyl-4-methyl-L-threonine (MeBmt) is replaced with L-threonine (Thr), was synthesized by the solid phase method. Its activity in the humoral response to sheep red blood cells in vitro and in vivo in mice was practically the same as that of cyclosporine A used as a standard, whereas the analogue studied exerted a significantly stronger effect in the delayed type hypersensitivity to sheep red blood cells in mice. PMID- 1495498 TI - Immunodominant structures of human growth hormone identified by homolog-scanning mutagenesis. AB - Homolog-scanning mutagenesis has been reported to be useful in elucidating the antigenic epitopes recognized by monoclonal antibodies and hGH binding to its receptor. However, little is known about which structures are recognized as immunodominant by murine serum antibodies. Therefore, the previously published series of hGH homologs and additional mutants of human placental lactogen (hPL), porcine growth hormone (pGH), and human prolactin (hPRL) were examined for their interaction with murine serum derived anti-hGH antibodies. As compared to wild type hGH, nine of the nineteen segment substituted mutants tested showed a significant reduction in binding to anti-hGH sera. These disruptive substitutions mapped to 5 regions on a structural model of hGH: the length of helix 1 (residues 11-33), the loop between the first disulfide bond and helix 2 (residues 54-74), the beginning of helix 3 (residues 109-112), the carboxyl half of helix 4 (residues 167-182), and the final carboxyl terminus segment of the molecule (residues 184-191). In terms of the current structural model, three of the five immunodominant regions (the loop between residues 54-74, central portion of helix 4 to the carboxyl terminus and part of the amino terminus region of helix 1) closely overlaps the hGH receptor binding epitopes. PMID- 1495499 TI - Influenza basic polymerase 2 peptides are recognized by influenza nucleoprotein specific cytotoxic T lymphocytes. AB - Cytotoxic T lymphocytes (CTL) play an important role in limiting viral infections and in eradicating virus from host tissues. Recent progress in understanding the processing and presentation of viral antigens to CTL indicates that the CTL antigen receptor recognizes peptides derived from viral proteins that are bound to an antigen binding groove present in class I major histocompatibility complex (MHC) molecules. In understanding CTL anti-viral responses and in creating vaccines designed to elicit CTL responses, it is critical to identify the portions of viral proteins that bind class I molecules and are recognized by T cell receptors. Previous findings have indicated that a significant portion of the CTL response of H-2d mice to influenza virus is specific for one of the viral polymerases (PB2). To identify the region of PB2 naturally processed and presented by influenza virus-infected mouse cells to CTL, 31 PB2 peptides of 9-16 residues in length were chosen and chemically synthesized. Two peptides, PB2, residues 146-159 and 187-195, were found to sensitize histocompatible target cells for recognition by influenza virus-specific CTL. When CTL were generated to individual viral proteins using influenza-vaccinia recombinant viruses, we found, to our surprise, that PB2-specific CTL failed to recognize cells sensitized with PB2 peptides 146-159 and 187-195. Further analysis showed that these PB2 peptides were, in fact, recognized by nucleoprotein (NP)-specific CTL generated by NP-vac virus priming and influenza A virus stimulation, or NP peptide stimulation in vitro of NP-vac or influenza A-primed CTL. These results demonstrate that while screening peptide libraries one cannot assume that positive peptides necessarily identify the viral protein to which the CTL response is directed. PMID- 1495500 TI - Possible use of similar framework region amino acid sequences between human and mouse immunoglobulins for humanizing mouse antibodies. AB - We have previously noted that a specific amino acid sequence could form the second framework region of human, mouse and rabbit immunoglobulin light chains, suggesting that this sequence has been preserved for 80 million years. Through divergent evolution, each species has acquired a different set of framework region sequences; however, these sets still share a few similar or identical amino acid sequences. In the present study, we have identified such sequences for all four framework regions between human and mouse immunoglobulin light and heavy chains. They may be useful in humanizing or reshaping mouse or rat antibodies for therapeutic applications in human patients. PMID- 1495502 TI - Nucleotide sequence of a nurse shark immunoglobulin heavy chain cDNA clone. PMID- 1495501 TI - The heterogeneity of bovine IgG2--V. Differences in the primary structure of bovine IgG2 allotypes. AB - The partial amino acid sequences of the gamma chains of the bovine IgG2a(A1) and IgG2a(A2) allotypes were determined. Sequence differences were found in the CH1 domain, the hinge region, and the CH3 domain. The hinge regions displayed only 71.4% similarity and all of the differences were of a radical nature. The A2 hinge has isoleucine instead of serine at 229, histidine for asparagine at 235, proline for histidine at 238, and cysteine instead of proline in position 234; the latter has the potential for forming an additional interheavy chain disulphide bridge. The occurrence of such a bridge could explain the presence of a pepsin fragment consisting of the hinge region and the Fc. A corresponding fragment is not obtained with the A1 allotype. Both allotypes have a shortened hinge region and a truncated CH2 domain. This feature is characteristic of all reported sequences of IgG2 proteins but not IgG1 in cattle and the goat. This structural feature may be important in subclass-specific recognition by Fc gamma receptors in ruminants. A surprising discovery was the occurrence of five substitutions in the CH3 domain of the IgG2a(A2) in comparison with the A1, which are shared with the CH3 of IgG1. These permit the occurrence of isoallotypic determinants and can explain the difficulty encountered in preparing A2-specific antisera during which adsorption with IgG1 is a routine procedure. The primary sequence data we report confirm the presence of major structural differences between the A allotypes of cattle that was suggested by previous work. The sequence of the A1 allotype most closely agrees with the two IgG2 sequences deduced from their nucleotide sequences whereas the sequence differences in the hinge and C-terminal CH3 make IgG2a(A2) unique. The structural differences between allotypes could have major consequences for such biological activities as phagocytosis, transepithelial transport, lymphocyte and complement activation. PMID- 1495503 TI - AAEM minimonograph #39: digital filtering: basic concepts and application to evoked potentials. AB - Filtering of evoked potentials has been performed in clinical laboratories using both analog and digital methods. Analog methods introduce distortion caused by nonlinear phase shift which may be quite severe. Digital methods, while avoiding distortion caused by phase shift, reveal evoked potential components which may or may not correspond to distinct singular neuroanatomic generators or homogeneous neuroanatomic systems. Thus, components identified with zero phase shift digital filters at restricted bandpass must be compared with components seen in open bandpass recordings. In some specific circumstances, high-pass filtering of short latency somatosensory-evoked potentials may distinguish slow asynchronous synaptic activity from fast and synchronous synaptic, lemniscal, or axonal activity. PMID- 1495504 TI - Lumbosacral nerve root stimulation comparing electrical with surface magnetic coil techniques. AB - Stimulation of lumbosacral nerve roots using a monopolar needle electrode was compared with magnetic stimulation using a 7-cm diameter surface coil. Compound muscle action potentials were recorded from the tibialis anterior (TA) and flexor hallucis brevis (FHB) muscles. Although the mean latency of CMAPs did not differ using the two techniques, amplitudes were considerably larger using a needle. Mean amplitudes were 66% (TA) and 64% (FHB) of the direct M response obtained by distal, supramaximal stimulation compared with mean values using maximal magnetic coil stimulation of 36% (TA) and 25% (FHB). Minimum F-wave latencies from FHB were used to estimate the site of nerve root stimulation using both techniques. Although there was a large amount of variability in the data from individual subjects, the results suggested that, on the average, both forms of stimulation act proximal to the intervertebral foramen. We conclude that a needle electrode is a more suitable technique for stimulating lumbosacral nerve roots. PMID- 1495505 TI - Severe acute axonal form of Guillain-Barre syndrome associated with IgG anti-GD1a antibodies. AB - We report cases of 2 patients with pure motor Guillain-Barre syndrome of explosive onset who required mechanical ventilation for more than 2 months. Their electrophysiologic findings and poor clinical recoveries suggested severe axonal degeneration involving the motor nerves. Enzyme-linked immunosorbent assay and thin-layer chromatogram-immunostaining showed the sera of both patients had high IgG antibody titer against GD1a ganglioside. Their titers decreased with the clinical course of the illness. GD1a as well as GM1, appears to be the target pathogenic antigen in motor axon disorders. Elevated IgG anti-GD1a antibody titer may prove useful for predicting severe GBS. PMID- 1495506 TI - The relative diagnostic sensitivity of different F-wave parameters in various polyneuropathies. AB - We studied F-wave minimum latency, persistence, and chronodispersion in the median and ulnar nerves of 70 controls and 75 patients with various polyneuropathies. Prolonged minimum latency was the most frequent F-wave abnormality in all groups of patients with polyneuropathy. The finding of decreased persistence or absence of F-responses was comparable in sensitivity to prolonged minimum latency in Guillain-Barre syndrome (GBS) and chronic inflammatory demyelinating polyneuropathy (CIDP), whereas chronodispersion had a comparable sensitivity only in CIDP. Decreased persistence of obtained F responses, and the absence of F-responses in nerves with low compound muscle action potential amplitudes, were nonspecific findings. F-wave studies often provide useful additional information in the evaluation of patients suspected of having a polyneuropathy. In patients with axonal polyneuropathies, we found that F-wave studies are significantly more sensitive than standard motor conduction studies in identifying physiological abnormalities of motor axons. Furthermore, in a patient with an acquired polyneuropathy, the finding of markedly prolonged minimum latency, or the absence of F-responses in nerves with normal CMAP amplitude, is highly specific for the presence of demyelination. PMID- 1495507 TI - Satellite cells in innervated and denervated muscles treated with clenbuterol. AB - The sympathomimetic agent, clenbuterol, induces a muscle-specific hypertrophy in both normal and catabolic muscle. Drug-induced hypertrophy is not generally associated with an increase in DNA content, thus the role of satellite cells in the response of soleus muscles from weanling rats is questioned. Following simultaneous sciatic section and administration of clenbuterol, responses are similar in innervated and denervated muscles after 4 days. Increased protein accretion in treated muscles is associated with evidence of satellite cell activation, but with little evidence of division. It is speculated that satellite cell production of growth factors may play an important role in the hypertrophic action of clenbuterol, and the clinical implications of the findings are discussed. PMID- 1495508 TI - Autonomic surface potential analysis: assessment of reproducibility and sensitivity. AB - There has been recent interest in measuring sympathetic sudomotor function by autonomic surface potential analysis. The purpose of the present study was to assess factors affecting the reproducibility of the test. We determined the within-day and between-day reproducibility in 24 healthy volunteers. We used an increasing rather than a constant electrical stimulus to minimize habituation. The amplitudes were still highly variable (an average within-day coefficient of variation in the soles of 35%). Habituation did not, however, affect the latencies of the responses, which were much more reproducible (an average within day coefficient of variation in the soles of 8%). Studies of between-day reproducibility revealed that the mean amplitudes were lower on day 2 vs. day 1 (0.706 +/- 0.10 vs. 0.85 +/- 0.10 mV in the soles, P less than 0.01) but the mean latencies were similar on the different testing days (2.09 +/- .04 seconds for the soles on day 1 vs. 2.16 +/- .05 seconds on day 2). We also assessed the sensitivity of surface potential analysis and report the results of testing 35 patients with far advanced autonomic neuropathy. PMID- 1495509 TI - Effects of phenytoin in two myotonic horses with hyperkalemic periodic paralysis. AB - The effects of phenytoin treatment were evaluated in 2 myotonic horses with hyperkalemic periodic paralysis (HPP). Phenytoin treatment abolished the clinical signs of muscle fasciculations following oral potassium challenge and decreased or abolished repetitive firing and myotonic discharges found on electromyographic examination. In both horses, an abnormally low threshold for calcium-induced calcium release was measured in heavy sarcoplasmic reticulum fractions from skeletal muscle, and this threshold increased with phenytoin treatment. Results suggest phenytoin is useful in modifying disordered ion regulation in the sarcolemma and sarcoplasmic reticulum of skeletal muscle in equine hyperkalemic periodic paralysis. PMID- 1495510 TI - Obstetrical lumbosacral plexus injury. AB - Injuries to the lumbosacral plexus during labor and delivery have been reported in the literature for years, but have lacked electrophysiologic testing to substantiate the location of the nerve injury. We report 2 cases with comprehensive electrophysiologic testing which localizes the site of this obstetrical paralysis to the lumbosacral trunk (L4-5) and S-1 root where they join and pass over the pelvic rim. The paralysis may be mild or severe. Small maternal size, a large fetus, midforceps rotation, and fetal malposition may place the mother at risk for this nerve injury. PMID- 1495511 TI - Increasing the proliferative capacity of muscular dystrophy myoblasts. AB - Temperature-sensitive immortalized neural cells may be utilized to produce genetically engineered neural transplants. We have used a similar approach with mdx myoblasts. Control and mdx myoblasts were immortalized with a recombinant retrovirus that effects the expression of a temperature-sensitive simian virus 40 large T antigen. The resultant cells divide indefinitely at 34 degrees C, but differentiate at 38 degrees C, both morphologically and immunocytochemically. Polymerase chain reaction analysis of RNA confirmed the presence of the dystrophin point mutation in the mdx cells and its absence in the control cells. A similar approach may be useful for the proliferation, modification, and reimplantation of autologous cells from patients with degenerative and dystrophic disorders such as Duchenne muscular dystrophy. PMID- 1495512 TI - Far-field potentials in circular volumes: the effect of different volume sizes and intercompartmental openings. AB - Preliminary investigations of circular volume conductors suggested that far-field potential magnitude declines progressively slower with increasing radial distance from a current source and follows a cosine function with angular displacement of the recording electrode from the electrical generator's axis. Using circular volumes of 6 differing radii, the mathematical relationship between angle, radii, and far-field potential amplitude is determined. Previous theoretical relationships of amplitude versus dipolar spacing, current, and distance from a dipole generator in a bounded volume conducting medium are verified for the near field. Far-field potentials in circular volumes are found to become constant at radii greater than 75% of the bounded volume's radius. Additionally, an adjoining volume conductor acts simply as a passive fluid-filled electrode (wick electrode) to the circular volume containing the generator until the intercompartmental opening to the circular volume exceeds 20% of its circumference. This finding was clinically supported by recording similar P9 somatosensory-evoked far-field potentials generated caudal to the foramen magnum from various portions of the cranium, whose connections to the torso, foramen magnum, and neck, average 6.2% and 17.8%, respectively. Finally, 3 circular volume conductors were connected in series by channels less than 20% of the volume conductor's circumference. Both adjoining circular volumes were equipotential to the far-field potential present at the boundary of the first circular volume containing the dipole generator. This observation supports the clinical finding of far-field potential transmission through multiple human bodies in conductive contact. PMID- 1495513 TI - Twin peaks, or the histographic analysis revisited. PMID- 1495514 TI - Electrophysiological mapping of the segmental anatomy of the muscles of the lower extremity. PMID- 1495515 TI - Idiopathic thrombocytopenic purpura and autoimmune thyroiditis in a patient with myasthenia gravis. PMID- 1495516 TI - MUAP analysis using Bayes classifier. PMID- 1495517 TI - Serotype of Campylobacter jejuni, HLA, and the Guillain-Barre syndrome. PMID- 1495518 TI - Twitch tension and mechanical delay latency in isolated skeletal muscle: effects of subcontracture potassium depolarization. PMID- 1495519 TI - In vitro glucose uptake by fast and slow skeletal muscles in dystrophic mice. PMID- 1495520 TI - Effects of the early administration of enalapril on mortality in patients with acute myocardial infarction. Results of the Cooperative New Scandinavian Enalapril Survival Study II (CONSENSUS II) AB - BACKGROUND: Long-term administration of angiotensin-converting--enzyme (ACE) inhibitors has been shown to improve survival in patients with symptomatic left ventricular failure and to attenuate left ventricular dilatation in patients with myocardial infarction. We studied whether mortality could be reduced during the 6 months after an acute myocardial infarction with use of the ACE inhibitor enalapril. METHODS: At 103 Scandinavian centers patients with acute myocardial infarctions and blood pressure above 100/60 mm Hg were randomly assigned to treatment with either enalapril or placebo, in addition to conventional therapy. Therapy was initiated with an intravenous infusion of enalapril (enalaprilat) within 24 hours after the onset of chest pain, followed by administration of oral enalapril. RESULTS: Of the 6090 patients enrolled, 3046 were assigned to placebo and 3044 to enalapril. The life-table mortality rates in the two groups at one and six months were not significantly different (6.3 and 10.2 percent in the placebo group vs. 7.2 and 11.0 percent in the enalapril group, P = 0.26). The relative risk of death in the enalapril group was 1.10 (95 percent confidence interval, 0.93 to 1.29). Death due to progressive heart failure occurred in 104 patients (3.4 percent) in the placebo group and 132 (4.3 percent) in the enalapril group (P = 0.06). Therapy had to be changed because of worsening heart failure in 30 percent of the placebo group and 27 percent of the enalapril group (P less than 0.006). Early hypotension (systolic pressure less than 90 mm Hg or diastolic pressure less than 50 mm Hg) occurred in 12 percent of the enalapril group and 3 percent of the placebo group (P less than 0.001). CONCLUSIONS: Enalapril therapy started within 24 hours of the onset of acute myocardial infarction does not improve survival during the 180 days after infarction. PMID- 1495521 TI - Neurocysticercosis in an Orthodox Jewish community in New York City. AB - BACKGROUND AND METHODS: From June 1990 through July 1991, intracerebral infection with the larval stage of the pork tapeworm Taenia solium was diagnosed in four unrelated persons in an Orthodox Jewish community in New York City. None of the patients had eaten pork, and only one had traveled to a country in which T. solium infection was endemic. We investigated this outbreak, screened serum samples from family members and household contacts for antibodies to cysticercosis, and examined stool specimens from household employees for eggs of taenia species. RESULTS: The four patients had recurrent seizures and brain lesions that were radiologically consistent with the presence of cysticerci. The diagnosis was confirmed in two patients by a brain biopsy, and in two by immunoblot assays for cysticercus antibodies. Of 17 immediate family members screened serologically, 7 from two families had cysticercus antibodies. Magnetic resonance imaging of the brain showed cystic lesions in two of the seropositive family members, one of whom had had a seizure. Examinations of six domestic employees from all four households revealed an active infection with taenia species in one and a positive serologic test in another. Since these women had recently emigrated from Latin American countries where T. solium infection is endemic, they were the most likely sources of infection in the members of these households. CONCLUSIONS: A diagnosis of neurocysticercosis should be considered in patients with seizures and radiologic evidence of cystic brain lesions, even in those who do not eat pork and who have not traveled to a country in which T. solium infection is endemic. Recent emigrants from countries in which T. solium infection is endemic should be screened for tapeworm infection in their stools before they are employed as housekeepers or food handlers. PMID- 1495522 TI - The course of seizures after treatment for cerebral cysticercosis. AB - BACKGROUND: Worldwide, cerebral cysticercosis is one of the most common causes of seizure disorders. Modern cysticidal drugs can usually eliminate the parasite from the brain, but there have been doubts as to whether such treatment improves the seizure disorder. METHODS: We studied 240 patients with seizures and cysticercosis of the brain parenchyma. Of these patients, 118 received cysticidal therapy (albendazole, praziquantel, or both) for lesions without inflammation on imaging studies (group 1); 49 patients with similar lesions either were not offered or refused cysticidal medication (group 2). Another 58 patients with inflammation around cysts (making spontaneous resolution more likely) also did not receive cysticidal medication (group 3), whereas cysticerci were removed surgically in 15 patients (group 4). The 240 patients were followed for a mean (+/- SE) of 92 +/- 7 months. RESULTS: In the patients treated with cysticidal medications, there was an 82 percent reduction in the mean number of brain cysts (from 5.0 to 0.9) and a 95 percent reduction in the mean frequency of seizures (from 11.3 to 0.6 per year; P less than 0.001). After three years of follow-up, 64 patients in group 1 (54 percent) were seizure-free. By contrast, the untreated patients (group 2) averaged 10.9 seizures per year; none were seizure-free. Among those with inflamed cysts (group 3), there was a 74 percent reduction in the frequency of seizures (from 7.5 to 2.7 per year), and 18 patients (31 percent) became seizure-free. After surgical treatment (group 4), there was an 87 percent reduction in the frequency of seizures (from 12.8 to 1.7 per year), and six patients (40 percent) became seizure-free. CONCLUSIONS: After medical treatment of neurocysticercosis, there is usually remission or marked improvement in the associated seizure disorder. PMID- 1495523 TI - Brief report: idiotypic IgA nephropathy in patients with human immunodeficiency virus infection. PMID- 1495524 TI - Carbohydrate metabolism in non-insulin-dependent diabetes mellitus. PMID- 1495525 TI - Case records of the Massachusetts General Hospital. Weekly clinicopathological exercises. Normal reference laboratory values. PMID- 1495526 TI - The prevention of heart failure--a new agenda. PMID- 1495527 TI - Tapeworm infection--the long and the short of it. PMID- 1495529 TI - Treating depression and anxiety in primary care. PMID- 1495530 TI - Treating depression and anxiety in primary care. PMID- 1495528 TI - HIV-associated nephropathies. PMID- 1495532 TI - Treating depression and anxiety in primary care. PMID- 1495531 TI - Treating depression and anxiety in primary care. PMID- 1495533 TI - Hypertension in pregnancy. PMID- 1495534 TI - Treating depression and anxiety in primary care. PMID- 1495535 TI - Hypertension in pregnancy. PMID- 1495536 TI - Hypertension in pregnancy. PMID- 1495537 TI - Erythropoietin therapy for uremic pruritus. PMID- 1495538 TI - Erythropoietin therapy for uremic pruritus. PMID- 1495539 TI - Central venous catheters and sepsis in patients with quadriplegia. PMID- 1495540 TI - Anaphylactic shock after retreatment with OKT3 monoclonal antibody. PMID- 1495541 TI - Health care in Eurasia. PMID- 1495542 TI - Clinical problem-solving: when to let go. PMID- 1495544 TI - High time for the circuses to stop. PMID- 1495545 TI - Managing Rio's treaties. PMID- 1495543 TI - The American health care system. Managed care. PMID- 1495546 TI - African National Congress drafts blueprint for South African science. PMID- 1495547 TI - NSF opens up long-range plan to public comments. PMID- 1495549 TI - Korea begins funding projects to catch up with rest of world. PMID- 1495548 TI - NSF unmoved by politics of relocation. PMID- 1495550 TI - Bovine growth hormone meets new safety concerns. PMID- 1495551 TI - University scientists to be investigated for conflicts of interest. PMID- 1495552 TI - US government asked to fund more industrial research. PMID- 1495553 TI - Frustrated by regulatory delays at FDA, biotech companies warm to user fees. PMID- 1495554 TI - Leeds inquiry. PMID- 1495555 TI - NIH patent rights. PMID- 1495556 TI - Defining consciousness. PMID- 1495557 TI - Frontiers future. PMID- 1495558 TI - Transcription. The tell-tail trigger. PMID- 1495559 TI - Coley's vaccine and TNF therapy. PMID- 1495560 TI - Human general transcription factor IIH phosphorylates the C-terminal domain of RNA polymerase II. AB - Phosphorylation of the carboxy-terminal domain of the largest subunit of RNA polymerase II is believed to control the transition from transcription initiation to elongation. The general transcription factor IIH (TFIIH) contains a kinase activity capable of phosphorylating this domain. Factors that promote the association of RNA polymerase II with the preinitiation complex stimulate this activity. The transcription factor IIE, which is required for the stable association of TFIIH with the preinitiation complex, affects the processivity of TFIIH kinase. PMID- 1495561 TI - Optical imaging of epileptiform and functional activity in human cerebral cortex. AB - Optical imaging of animal somatosensory, olfactory and visual cortices has revealed maps of functional activity. In non-human primates, high-resolution maps of the visual cortex have been obtained using only an intrinsic reflection signal. Although the time course of the signal is slower than membrane potential changes, the maximum optical changes correspond to the maximal neuronal activity. The intrinsic optical signal may represent the flow of ionic currents, oxygen delivery, changes in blood volume, potassium accumulation or glial swelling. Here we use similar techniques to obtain maps from human cortex during stimulation evoked epileptiform afterdischarges and cognitively evoked functional activity. Optical changes increased in magnitude as the intensity and duration of the afterdischarges increased. In areas surrounding the afterdischarge activity, optical changes were in the opposite direction and possibly represent an inhibitory surround. Large optical changes were found in the sensory cortex during tongue movement and in Broca's and Wernicke's language areas during naming exercises. The adaptation of high-resolution optical imaging for use on human cortex provides a new technique for investigation of the organization of the sensory and motor cortices, language, and other cognitive processes. PMID- 1495562 TI - Nitric oxide release from a single cell measured in situ by a porphyrinic-based microsensor. AB - Nitric oxide is an important bioregulatory molecule, being responsible, for example, for activity of endothelium-derived relaxing factor (EDRF). Acute hypertension, diabetes, ischaemia and atherosclerosis are associated with abnormalities of EDRF. Nitric oxide is thought to be a retrograde messenger in the central nervous system. The technology is not yet available for rapid detection of NO released by a single cell in the presence of oxygen and/or nitrite, so the release, distribution and reactivity of endogenous NO in biological systems cannot be analysed. Here we describe a porphyrinic microsensor that we have developed and applied to monitoring NO release in a microsystem. We selectively measured in situ the NO released from a single cell with a response time of less than 10 ms. The microsensor consists of p-type semiconducting polymeric porphyrin and a cationic exchanger (Nafion) deposited on a thermally sharpened carbon fibre with a tip diameter of approximately 0.5 microns. The microsensor, which can be operated in either the amperometric or voltammetric mode, is characterized by a linear response up to 300 microM and a detection limit of 10 nM. Nitric oxide at the level of 10(-20) mols can be detected in a single cell. PMID- 1495563 TI - [Invagination: the importance of early diagnosis]. PMID- 1495564 TI - [Educational inspection of medicine and health sciences; a glimpse of the final report]. PMID- 1495566 TI - [Prevention of congenital toxoplasmosis]. PMID- 1495565 TI - [Moclobemide (Aurorix), the first MAO-A-inhibitor: really something new?]. PMID- 1495567 TI - [Saliva as an alternative for blood in the isolation of HIV antibodies]. PMID- 1495568 TI - [Variation in serum cholesterol level in the same person: what is the true value and when is it called a significant change?]. AB - The blood cholesterol level is not constant over time. Changing values may be found when rechecking high values, especially in patients on a diet or receiving medication. Repeated measurements are necessary. It will then be possible to estimate the 'true mean value'. This is the theoretical average of a large number of measurements taken from one person. The study concentrated on the intra individual variation of the serum cholesterol and the consequences for screening and follow-up. For this purpose, during a period of four weeks, cholesterol levels were measured 12 times in 33 men aged 25-40. The mean coefficient of variation was 5.7%, with wide differences between participants, ranging from 2.9% to 9.8%. The position of the 'true mean value' was estimated (with 90% confidence), after I resp. 3 determinations. These findings have consequences for the classification of subjects in the different risk categories as defined in the Dutch Cholesterol Consensus. It is also possible to determine if, after a period of intervention, there is a significant decline in the cholesterol level. Roughly, a decline of 10-12% indicates a significant difference. PMID- 1495569 TI - [Effect of short-term use of omega-3-type polyunsaturated fatty acids in subjects with hypertriglyceridemia]. AB - OBJECTIVE: To study the effect of omega-3 polyunsaturated fatty acid supplementation on lipid profile in hypertriglyceridaemic patients. SETTING: General practice. DESIGN: Prospective, double blind study of 12 weeks' duration. PATIENTS AND METHODS: Eight patients received fish oil (1800 mg C20: 5 omega-3 eicosapentaenoic acid (EPA) and 1200 mg C22:6 omega-3 docosahexaenoic acid (DHA). Nine patients received corn oil (3000 mg C18: 2 omega-6 linoleic acid daily). RESULTS: Lipid profile analysis showed a decrease in triglyceride levels after fish oil supplementation. An unexpected and unexplained finding was the rise in total cholesterol and LDH cholesterol with corn oil supplementation. CONCLUSION: Fish oil causes a decrease in triglyceride levels in hypertriglyceridaemic patients. PMID- 1495571 TI - [Simple ligation better than invagination of the appendix stump; a prospective randomized study]. PMID- 1495570 TI - [Functioning of an Exercise electrocardiographic service for family physicians; a report of 498 patients]. AB - OBJECTIVE: In Rotterdam GPs have the possibility of requesting an exertion ECG for their patients from the Foundation Thrombosis Service and Physicians' Laboratory. A follow-up study was carried out in order to gain insight into the functioning of this service. PATIENTS AND METHODS: Over a period of three months, 266 GPs referred 498 patients to the service for an exertion ECG. The GPs received an enquiry form with questions on the referral and the functioning of the service. The patients were followed up for two weeks in connection with any (cardiovascular) events and with the management by the GP. An ECG was regarded as positive if the ST showed a depression greater than or equal to 1.5 mm. RESULTS: None of the patients died during the period of the investigation. Of the patients with positive and with negative ECGs, 41% and 37%, respectively, had no more complaints, 40% and 28% the same complaints, and 3% and 0.5% more complaints. Of the patients with a negative ECG (n = 439), 3.9% were referred to a cardiologist. If no ECG had been made, this proportion would have been 39%. CONCLUSION: The Foundation Thrombosis Service and Physicians' Laboratory Rotterdam provides an essential contribution to GPs' decision making concerning referral of patients with vague cardiac complaints to a cardiologist. PMID- 1495572 TI - [Oncogenes, tumor suppressor genes and the medical genetics of cancer]. PMID- 1495573 TI - Annual meeting of the World Federation of Neurology--Research Group on Neuroepidemiology. San Diego, California, May 4, 1992. Abstracts. PMID- 1495574 TI - Vascular dementia: a clinical and death certificate study. AB - We compared the extent of documentation of the diagnoses, vascular dementia and stroke, on inpatient (hospital) medical records and death certificates among 23 multi-infarct dementia index cases and 14 multi-infarct controls without cognitive dysfunction who were enrolled in a hospital-based case-control study and were followed longitudinally. Both the inpatient medical records and the death certificates markedly under-diagnosed vascular dementia when compared to the case-control study diagnosis. Furthermore, the diagnosis of stroke was grossly underdiagnosed on the death certificates. In lieu of the lack of medical record and death certificate documentation of vascular dementia, studies that utilize such information may be in considerable error. Clarification of the criteria for the diagnosis of vascular dementia and greater physician and public awareness of vascular dementia are needed. PMID- 1495575 TI - Diurnal and seasonal variations in the occurrence of stroke: a community-based study. AB - Several hospital-based studies suggest a circadian rhythm for stroke, with a peak of onset in the morning. To verify whether these results could be confirmed in a community-based study, we used data from the SEPIVAC, a community-based stroke register in Umbria, Italy. Cerebral infarctions (48%), primary intracerebral hemorrhages (54%), subarachnoid hemorrhages (53%) and 'not known' strokes (51%) were all more common between 6 a.m. and noon, and this peak was still present when strokes recognized on awakening were evenly redistributed over the sleep period. Looking at the subgroups of cerebral infarction, lacunar syndromes were more common during sleep. Cerebral infarctions were more frequent during winter, and primary intracerebral hemorrhages during autumn. PMID- 1495576 TI - Mortality rates for Parkinson's disease and parkinsonism in Italy (1969-1987). AB - The mortality rates (MRs) for Parkinson's disease (PD) and parkinsonism were analyzed for the period 1969-1987 in Italy, considering the population aged greater than or equal to 25. MRs were then age-adjusted taking the 1981 Italian population as standard. We found an increase in MRs for PD during the period studied. The Italian average annual age-adjusted MR was 5.73, ranging from 4.76 (1969) to 6.81 (1985). Moreover we noticed some interesting differences in the geographic distribution of MRs between the five big areas Italy was divided into. We also found that, while the MR for the ages 65-79 years was quite constant in the period studied, there was a marked increase in the MR for ages greater than 79 years from 1980 onwards. The geographic differences we found in MRs deserve to be analyzed in further epidemiological studies. PMID- 1495578 TI - HLA determinants in familial multiple sclerosis. AB - HLA-A, -B, -C, -DR, -DQ antigens were studied in 11 multiplex MS families, 11 single-case MS families and 100 healthy subjects. The HLA DR4 was the most frequent antigen in all MS patients (p = 0.015). When the antigenic frequency in index familial cases was compared with that in single cases, the DR4 antigen was found to be more frequent (p = 0.01) in familial cases only. Furthermore, when the DR4 antigen was excluded from the analysis, we observed an increase in DR2 (p = 0.11) only in the familial MS cases. These results can be compatible with a multifactorial hypothesis according to which the HLA genes have an important role in MS susceptibility in familial cases. PMID- 1495577 TI - A large-scale study of epilepsy in Ecuador: methodological aspects. AB - The methodology is presented of a large-scale study of epilepsy carried out in a highland area in northern Ecuador, South America, covering a population of 72,121 people; The study was carried out in two phases, the first, a cross-sectional phase, consisted of a house-to-house survey of all persons in this population, screening for epileptic seizures using a specially designed questionnaire. Possible cases identified in screening were assessed in a cascade diagnostic procedure applied by general doctors and neurologists. Its objectives were: to establish a comprehensive epidemiological profile of epileptic seizures; to describe the clinical phenomenology of this condition in the community; to validate methods for diagnosis and classification of epileptic seizures by a non specialised team; and to ascertain the community's knowledge, attitudes and practices regarding epilepsy. A sample was selected in this phase in order to study the social aspects of epilepsy in this community. The second phase, which was longitudinal, assessed the ability of non-specialist care in the treatment of epilepsy. It consisted of a prospective clinical trial of antiepileptic therapy in untreated patients using two standard anti-epileptic drugs. Patients were followed for 12 months by a multidisciplinary team consisting of a primary health worker, rural doctor, neurologist, anthropologist, and psychologist. Standardised, reproducible instruments and methods were used. This study was carried out through co-operation between the medical profession, political agencies and the pharmaceutical industry, at an international level. We consider this a model for further large-scale studies of this type. PMID- 1495579 TI - Multiple sclerosis in the Faroe Islands and the lack of protection by exposure in infancy. AB - Using data from 32 patients with symptom onset between 1943 and 1973, we described the occurrence of clinical neurologic multiple sclerosis (CNMS) in the Faroe Islands as then constituting three epidemics. We concluded that CNMS is the rare late result of infection with the primary MS affection (PMSA), a state requiring some 2 years of exposure for acquisition by Faroese. Our theses are that PMSA was first transmitted during World War II by affected by asymptomatic British troops to Faroese aged 11-45; that this (F1) cohort of affected asymptomatic Faroese under age 27 in 1945 transmitted PMSA to the next (F2) cohort of Faroese comprising those attaining age 11 each year from 1945 until F1 input ceased; that the F2 cohort similarly transmitted PMSA to the third (F3) cohort of Faroese. Cases of CNMS defining epidemics I-III were members of the respective F1-F3 cohorts. Within the F4 cohort of Faroese there is now a fourth epidemic of CNMS, with 7 patients with symptom onset between 1984 and 1989. Intermittency of the year of birth for CNMS cases is thus a reflection of membership in these separate population cohorts, and does not indicate 'protection' in infancy or childhood. There is no evidence for an extra-Faroese source of MS after the first epidemic. No model of acute infection with short transmissibility fits the data. PMID- 1495580 TI - [Transanal endoscopic microsurgery: technique and clinical results]. AB - A new system has been developed for transanal endoscopic microsurgery (TEM), which allows all the conventional surgical techniques within the rectal cavity. The main indication is the removal of sessile adenomas. "Early rectal carcinomas" are also suitable for local excision. We perform local excision of advanced cancer only in cases where a contraindication exists to perform radical surgery or when the patients is unwilling to undergo demolitive surgery. The system has been employed at our Surgical Department on 206 patients in 223 cases. In 192 cases (87.7%) only one local excision was carried out due to sufficient excision as confirmed by histology (including patients with early "low risk" cancer). the postoperative course of 208 cases (93.3%) was free from any complications. The recurrence rate of adenomas amounted to 5.2%. This technique is particularly applicable for elderly, high risk patients and those with broad based adenomas so that anterior resection, abdominoperineal resection or other invasive operations can be avoided. PMID- 1495581 TI - [Abdominal visceral lesions in patients with multiple trauma]. AB - The paper describes a series of 385 cases of multiple injuries which were treated between 1987 and 1991 at the Emergency Unit of the Fatebenefratelli Hospital in Milan. Special attention was paid to abdominal trauma and visceral injuries in terms of both diagnosis and treatment. PMID- 1495582 TI - [Subdiaphragmatic aortic clamping in abdominal hemorrhagic emergencies]. AB - The paper describes a technique of subdiaphragmatic aortic clamping as a provisional method to stop blood flow in abdominal hemorrhage emergencies. The numerous indications for the method and satisfactory results obtained by its use are described. PMID- 1495583 TI - [Thymostimulin immunoprophylaxis in elective abdominal surgery]. AB - The Authors report their experience of 121 patients who had undergone an elective abdominal operation and who had been previously considered under an immunological point of view and classified as anergic. The Authors have found a notable reduction of postoperative infection incidence in the 61 anergic operated patients who have been treated with Thymostimulin; they conclude by underlining the importance of careful consideration and eventual correction of immunological alterations of the patients of the patients who must undergo an operation. PMID- 1495584 TI - [Antibiotic prophylaxis in surgery. Results of a 4-year personal case series]. AB - A prospective study of surgical infections in our Department of Surgery in the years 1986-1989 is reported. 2719 patients entered the study: they represent the total number of patients operated in the above said period (628 urgent and 2091 elective operations). As suggested in 1964 by Altmeier, surgical procedures were classified in four groups according to the potential risk of intraoperative contamination. For every septic complication observed pertinent cultures were performed and responsible pathogens identified. We present our protocol of antibacterial prophylaxis which distinguishes antibiotics given as "ultra short term", "short term", "antibiotic prophylaxis". The results obtained and particularly the total number of infections (3.9%), and the percentage of infections in group 3 (4.6%) and in group 4 (23.1%) procedures validate the usefulness of antibiotic prophylaxis in these patients. In group 1 and group 2 patients the usefulness of antibiotic prophylaxis seems very doubtful. PMID- 1495585 TI - [Mirizzi's syndrome type II: a diagnostic and therapeutic problem]. AB - The paper reports a case of cholestatic icterus caused by a large calculus in the infundibulum of the gallbladder with a cholecysto-choledochal fistula and hepato choledochal block (Mirizzi's type II syndrome). The diagnostic iter complicated the evolution, raising questions regarding the therapeutic strategy. PMID- 1495586 TI - [Porcelain gallbladder. Case reports]. AB - The Authors report some observations on gallbladder calcification with the presentation of two clinical cases. The pathologic anatomy and the clinical aspects of this infrequent affection are described. The Authors underline the importance of surgical treatment, considering the frequency of carcinoma in porcelain gallbladder. PMID- 1495587 TI - [Leiomyoma of the small intestine. Case report]. AB - The paper reports the case of a 53-year-old man admitted to hospital with melena. The initial diagnosis was bleeding duodenal ulcer; after 8 weeks of therapy the duodenal ulcer was completely healed, but renewed intestinal bleeding occurred three months later. Angiography of the upper mesenteric artery revealed a clear tumour form. A tumour of the small intestine the size of a fist was found during surgery. An ileal resection was performed. Histopathological tests confirmed the diagnosis of leiomyoma of the small intestine. PMID- 1495589 TI - [Mayer-Rokitansky syndrome. Case report]. AB - Uterine anomalies associated with congenital renal agenesis and skeletal abnormalities represent an uncommon pathology that often presents important diagnostic problems. A case of Mayer-Rokitansky syndrome is reported. The embryologic, clinical, pathologic and therapeutic implications of this disease are briefly discussed. PMID- 1495588 TI - [A rare case of breast ectopy associated with partial agenesis of osteo-muscular structures of the thoracic wall. Proposal of an original reparative technique]. AB - The Authors report a case of chest wall malformation characterized by costal defect (6th and 7th ribs), hypoplasia of the serratus and pectoralis major muscles, left mammary ectopy and mucoviscidosis. The case is reported because of the very singular malformative association and the originality of the reparative procedure. Appearance has been improved and a good shape and breast projection achieved. PMID- 1495590 TI - [Verneuil's suppurative hidradenitis. A case report]. AB - The Authors reports a case of Verneuil's disease in a perineal location. They focus on etiopathogenetic aspects and problems of differential diagnosis, before reviewing the various therapeutic options. Surgery is the only effective therapy and takes the form of an extensive excision of the cutaneous zone affected with 2nd intention recovery, or a dermoepidermal auto-graft. A long follow-up is important to monitor the possible recurrence of lesions generally due to the incomplete removal of the area affected by the process. PMID- 1495591 TI - [Peripheral neoplastic embolism. A rare pathology]. AB - The paper reports case of tumour embolus which was brought to the Authors' attention. Proposals for treating for this rare pathology are outlined following a review of the literature. PMID- 1495592 TI - [Role of loco-regional anesthesia in the surgical treatment of atheromatous lesions of the carotid bifurcation]. AB - The Authors report a case of carotid bifurcation endarterectomy under loco regional anesthesia. Despite a stump pressure of 44 mmHg, considered by the most of the Authors, the borderline value for carotid endarterectomy without shunt, the patient had a cerebral ischemic attack after 30 seconds of carotid clamping. So, the local anesthesia represents a valid alternative in order to detect an intolerance to clamping and underlines the importance of cerebral protection in this kind of surgical approach. PMID- 1495593 TI - Living on borrowed time. PMID- 1495594 TI - Practice tip. PMID- 1495595 TI - A practical, step-by-step approach to stress management for women. AB - Stress is a significant threat to the physical and emotional health of contemporary American women. Primary health care providers are an excellent resource for women in need of education about the seriousness of stress. Clinicians can work with women to prevent unnecessary exposure to stressors and to help them learn adaptive coping skills. This article offers a practical, step by-step approach to stress management for women. Assessment processes, planning concepts and relevant intervention strategies are discussed. PMID- 1495596 TI - Recognizing and managing mycobacterial diseases in clients with AIDS. AB - Mycobacterial diseases are common in people infected with human immunodeficiency virus. Mycobacterium tuberculosis (MTB) and Mycobacterium avium intracellulare (MAI), the specific pathogens most frequently involved, cause pulmonary tuberculosis and disseminated MAI infections. Pulmonary tuberculosis incidence was on the decline from 1950 to 1985, but since 1985 has been on the rise worldwide. Prior to the onset of AIDS, MAI infections were rare in humans. However, disseminated MAI seems to be associated with the terminal stage of AIDS. The symptomatology of MTB and MAI infections is similar, yet diagnosis and treatment vary. Pulmonary TB can be treated effectively with chemotherapy and isolation to prevent transmission. Because MAI infection is not a communicable disease, isolation is not necessary. Effective treatment for disseminated MAI remains under investigation; currently, a regimen of four to five drugs is recommended. There are however, significant side effects associated with this therapy. Because the number of AIDS patients is increasing, it is imperative for clinicians to understand the mycobacterial diseases and how best to manage them. PMID- 1495597 TI - Efficacy of transdermal nicotine patches for nicotine replacement and smoking cessation. PMID- 1495598 TI - Newborn's pain apparent during circumcision. PMID- 1495599 TI - Roles defined by mindset and context. PMID- 1495600 TI - Consider chiropractic management of thoracic outlet syndrome. PMID- 1495601 TI - Marketing yourself in an interview. PMID- 1495602 TI - A wedding to remember. PMID- 1495603 TI - A.A.C.N. recommendations. Addressing H.I.V. and hepatitis B. PMID- 1495604 TI - Documenting telephone orders. PMID- 1495605 TI - Taking a closer look at needle sticks. PMID- 1495606 TI - Recognizing epiglottitis. PMID- 1495607 TI - Understanding adverse drug reactions. PMID- 1495608 TI - Close-up on clavicle fracture. PMID- 1495609 TI - The last days of Helen Banks. PMID- 1495610 TI - Planting seeds of hope. PMID- 1495611 TI - The nurses I'll never forget. PMID- 1495612 TI - Does the gender gap affect your pain-control decisions? PMID- 1495614 TI - 10 tips for easing the pain of intramuscular injections. PMID- 1495613 TI - Getting to know the real Becky. PMID- 1495615 TI - Practical ways to survive a lawsuit. PMID- 1495616 TI - What's new in prehospital care. PMID- 1495617 TI - Using transesophageal echocardiography to assess the heart. PMID- 1495618 TI - Dylan's lesson. PMID- 1495619 TI - Myths & facts ... about pediatric patients. PMID- 1495620 TI - Administering blood therapy safely. PMID- 1495622 TI - [To denounce or not a colleague: a conflict of values]. PMID- 1495621 TI - One of the family. PMID- 1495623 TI - [Health assisted by computer]. PMID- 1495624 TI - [On the road to expertise]. PMID- 1495625 TI - Some answers and even more. PMID- 1495626 TI - [Sexual misconduct in nursing care]. PMID- 1495627 TI - [Tobacco usage among nurses]. PMID- 1495628 TI - [The family interview. A directable experience]. PMID- 1495629 TI - [When the hospital moves to the home]. PMID- 1495630 TI - Self-assertiveness at work. PMID- 1495631 TI - [Intervention plans. A philosophy to share]. PMID- 1495632 TI - Fractures of the mandible: role of the general dentist. AB - Mandibular fractures are the second most common facial fracture, the majority being the result of interpersonal violence, road traffic accidents, or sports injuries. Although most of these patients attend a hospital, it is not uncommon for patients with these injuries to present first to the general dentist, perhaps complaining of a loose tooth or abnormal bite. A careful history should be taken from the patient in order to identify the possibility of other injuries. Mandibular fractures are rarely life-threatening, although airway difficulties can arise. A systematic approach to diagnosis is essential if fractures are not to be missed, including radiological assessment in two planes at right angles. The initial treatment consists of airway management, control of fracture segments, and pharmacologic management. Most fractures have been traditionally managed by the use of intermaxillary fixation; however, increasing use is being made of open reduction and internal fixation techniques. Occasionally, general dentists are involved in the post-operative care of the patient following definitive management. PMID- 1495634 TI - The copy denture technique. AB - The copy denture technique facilitates the replication of the good feature of existing dentures. Assessment of the existing dentures provides essential information for diagnosis and treatment planning. Copy templates are made which exhibit those features of the existing dentures which are satisfactory and are to be reproduced in the new dentures, while facilitating controlled and predictable modification of undesirable features. All impressions and occlusal registrations are obtained with the aid of the templates which then provide stable trial bases. The patient may adapt to the new dentures quicker because of the reproduction of familiar features. PMID- 1495633 TI - Dentures, prosthetic treatment needs, and mucosal health in an institutionalised elderly population. AB - A survey of 359 elderly residents of rest homes and geriatric hospitals in the Manawatu and Horowhenua regions showed that 80.5 percent were fully edentulous. Full upper and lower dentures were worn by 64 percent of the total sample, and 31 percent of the dentate group wore one or more partial dentures. Prosthetic treatment needs were dominated by full dentures: 18 percent of upper dentures and 26 percent of lower dentures were considered to need replacement. A further 24 percent of full lower dentures required relining. Only 7 percent of the dentures were named. One third of the subjects had mucosal lesions, the most common lesions being angular cheilitis (present in 18 percent of subjects), traumatic ulcers (14 percent), atrophic glossitis (12 percent), and leukoplakia (present in 8 percent of subjects). No malignant lesions were found. PMID- 1495635 TI - Zygomatic bone fractures complicated by retrobulbar haemorrhage. AB - The two patients described in this report demonstrate retrobulbar haemorrhage as a complication of zygomatic bone fracture. Successful treatment of this rare but very serious complication involves urgent consultation with an ophthalmology service, and immediate medical and surgical management. It is extremely important to check the vision of patients with zygomatic bone fracture, before and after surgery, and consideration should be given to obtaining an ophthalmology opinion for all fractures involving the orbit. A simple examination, which every dentist should be able to perform, should include inspection of the eye, a test of visual acuity, testing eye movements, testing visual fields, reaction of the pupils, and an examination for proptosis. PMID- 1495636 TI - Infiltration analgesia of primary mandibular molars. PMID- 1495637 TI - Oral problems in children with malignancy. PMID- 1495638 TI - Antimicrobial therapy and periodontal disease. PMID- 1495639 TI - Prophylaxis for patients with artificial joints? PMID- 1495640 TI - Medications and dental care. PMID- 1495641 TI - Sorbitol--safe for teeth. PMID- 1495642 TI - A Kiwi solution. PMID- 1495644 TI - Postgraduate education. PMID- 1495643 TI - The DMF index. PMID- 1495646 TI - AIDS in New Zealand. PMID- 1495645 TI - Trends in dental health. PMID- 1495648 TI - Health funding changes and comprehensive services for the elderly. PMID- 1495647 TI - Selenium status of Christchurch infants and the effect of diet. AB - OBJECT: New Zealanders, because of a soil deficiency, have a low intake of selenium. To determine the impact of this on the infant population in Christchurch. METHODS: we have measured red cell and plasma selenium and the selenoenzyme, glutathione peroxidase, in 70 infants less than 12 months old and related these to age and diet. RESULTS: the infant population as a whole had mean plasma levels of selenium and glutathione peroxidase of 33 micrograms/L and 97 U/L compared with adult values of 74 micrograms/L and 150 U/L. Infant red cell levels of 0.30 mu g selenium and 9.0 U glutathione peroxidase per g haemoglobin were similar to those in adults. The selenium status of most breast fed infants after birth remained similar to that of cord blood. Mean plasma selenium and glutathione peroxidase levels in formula fed infants were about half those of breast fed infants, and their red cell selenium was also significantly lower. These did not increase until solids were introduced into the diet. The status of the infants reflected their diet, with the concentration of selenium in formulae being 3.9-5.2 micrograms/mL compared with a mean of 13.4 micrograms/mL in breast milk. CONCLUSIONS: since infants in more replete selenium areas show a gradual rise in blood selenium parameters after birth, this study suggests that formula fed and some breast fed infants in Christchurch receive an inadequate selenium intake. Consideration should be given to supplementing infant formulae and perhaps also the diet of pregnant and/or breast feeding mothers. PMID- 1495649 TI - Audit of prioritisation for coronary revascularisation procedures: implications for rationing. AB - OBJECTIVE: to audit prioritisation of patients awaiting coronary revascularisation. DESIGN: the case records of 92 Christchurch patients referred for coronary artery bypass surgery (CABG) or percutaneous transluminal angioplasty (PTCA) from January to April 1990 were reviewed. The actual waiting time was compared with a nominally optimal waiting time, determined from an urgency rating score based primarily on severity of angina and coronary anatomy. RESULTS: of 56 patients referred for CABG, 47 had left main or multivessel disease including proximal stenosis of the left anterior descending artery. Fifty had Canadian class III or IV angina and 18 had impaired left ventricular function. At the time of review (January 1991), 16 had not yet had an operation. The mean waiting time was at least 163 (SD 116) days. Only nine (16%) had CABG within the maximum optimal time. Thirty-six patients had PTCA within eight months, mean waiting time 80 (53) days. These patients had less severe disease, but similar severity of angina. Nineteen (53%) had their procedure within the optimal period. CONCLUSION: waiting times for coronary revascularisation are excessive, even for high risk patients. Prospective monitoring of the waiting list using a standardised urgency rating score is likely to provide useful information on the dynamics of the waiting list for coronary revascularisation. Furthermore, the effects of further rationing of services can be analysed. PMID- 1495650 TI - Outpatient clinic nonarrivals and cancellations. AB - OBJECTIVES: outpatient clinics account for much of the work and expenditure in public hospitals. Many hospitals are trying to improve clinic efficiency. This research was conducted to assess the extent and characteristics of outpatient nonarrivals and cancellations at Dunedin Hospital, and to make suggestions for improvements. METHODS: data on 37,271 appointments scheduled during six months of 1990 were obtained. Nonarrivals and cancellations were examined in relation to characteristics of the patient, clinic and appointment. RESULTS: a large proportion (21.2%) of the appointments were not completed, comprising 8.3% nonarrivals, 7.5% patient cancellations, and 5.4% clinic cancellations or reschedulings. Nonarrivals were related to characteristics of the patient; including age, sex, ethnic group, and marital status. The proportions of nonarrivals and cancellations varied among different clinics. For new appointments, longer waiting times from referral were related to nonarrivals and patient cancellations. CONCLUSIONS: outpatient nonarrivals and cancellations pose a large problem at Dunedin Hospital. They could be reduced if some clinics provided more information for patients, arranged better cover for consultant absences, minimised clerical errors, decreased waiting times for new referrals, and used patient reminders. PMID- 1495651 TI - Motor vehicle road crashes during the fourteenth and fifteenth years of life. AB - From a sample of 848 teenagers, 50 individuals reported a total of 52 motor vehicle road crash events: 42 involved a car, six a motorcycle, and four a bus, over a two year period. Males and females were equally represented in each type of crash. Twenty-one of the car crashes, four of the motorcycle crashes and three of the bus crashes involved injury. The injuries sustained in the motorcycle crashes were predominantly to the extremities and in the other crashes they were mainly to the head or face. On average drivers less than 25 years of age had more passengers in their cars and were involved in more nighttime crashes. A seat belt was worn in only 18 (44%) of the car crashes. A motorcycle helmet was worn in four of the six motorcycle crashes. Six (15%) crashes were reported to have involved alcohol. The main areas of risk associated with motor vehicle road crashes involving teenagers and young adults have been addressed by legislation or the graduated drivers' licensing system. An evaluation of these measures is required to establish whether they are effective. PMID- 1495652 TI - Myasthenia gravis presenting as respiratory failure. PMID- 1495653 TI - The effect of the increased prescription charges on the collection of asthma drugs. PMID- 1495654 TI - Fish oil in the treatment of hypertension. PMID- 1495655 TI - Subsidising rural practice. PMID- 1495656 TI - Bed sharing as a risk factor for sudden infant death (cot death) PMID- 1495657 TI - Nontoxigenic strains of diphtheria. PMID- 1495658 TI - HIV antibodies in used syringes. PMID- 1495659 TI - How well are we protecting our children? An immunisation coverage survey in Hawke's Bay. AB - AIMS: In July 1991, an immunisation coverage survey was conducted to assess the proportion of two year old children who have been vaccinated in the Hawke's Bay. METHODS: Parents from a representative sample of 100 households with children between the ages of two and four years of age were interviewed regarding household characteristics and parental attitudes towards immunisation. Immunisation histories were abstracted from each child's Health and Development Record Book or, if this was not available or was incomplete, from records retained by the general practitioner(s) responsible for administering immunisations to the child. RESULTS: Coverage levels among two year olds exceeded 85% for all postneonatal vaccinations scheduled for the first year of life; however, levels among two year olds were lower than 85% for all vaccinations scheduled to be received after the first birthday. Overall, only 61% (95% confidence interval (CI) = 50.7, 70.6) of the children were fully vaccinated by the age of two years. Children living in a household where the principal source of income was from benefits were almost 60% less likely to have been fully immunised at two years of age (odds ratio (OR) = 0.42, 95% CI = 0.18, 0.97), as were Maori children (OR = 0.43, 95% CI = 0.18, 1.06). CONCLUSIONS: These results emphasise the need for enhanced education about the importance of completing the full series of recommended vaccinations and of on-time vaccination, as well as for checking childrens' vaccination histories at every contact with the healthcare system and, where necessary, administering past-due immunisations. PMID- 1495660 TI - The 1991 measles epidemic: how effective is the vaccine? AB - AIM: To estimate measles vaccine efficacy in the field in New Zealand, during the 1991 measles epidemic. METHODS: Notifications in the Wellington Area Health Board region from the first 21 weeks of the 1991 measles epidemic (1444 cases) were analysed to estimate vaccine efficacy. Estimates of 70% and 80% immunisation coverage were used in this analysis for the age groups of 1-4 years, 5-9 years, 10-14 years, and 15-19 years. RESULTS: A trend was demonstrated, suggesting a reduction in vaccine efficacy (VE) for the two older age groups at 70% coverage (1-4 years 69% VE, 5-9y 68%, 10-14y 46%, 15-19y 47%) and 80% coverage (1-4y 82%, 5-9y 81%, 10-14y 69%, 15-19y 69%). Potential sources of bias are highlighted and their impact on the vaccine efficacy estimates discussed. CONCLUSIONS: There are multiple sources of bias that exist. If New Zealand is to improve and monitor the quality of its vaccination programmes, good quality information is required, which may include the need for immunisation registers, or ongoing case control studies in certain circumstances. PMID- 1495661 TI - Beneficial effect of simvastatin in patients with drug resistant familial hypercholesterolaemia. AB - AIMS: To investigate the effects of simvastatin in patients with heterozygous familial hypercholesterolaemia refractory or intolerant to routine drug therapy. METHOD: Eighteen patients were given increasing doses of 10, 20 and 40 mg simvastatin for eight week periods, followed by a control period on their former drug therapy in a prospective, crossover clinical study. RESULTS: Mean total and low density lipoprotein cholesterol (SEM) were significantly lower on 40 mg simvastatin alone than at the end of the control period (7.3 (0.3) mmol/L vs 10.7 (0.4) and 5.1 (0.3) vs 7.8 (0.5) respectively; p less than 0.01). Apo-B was also significantly lower on 40 mg simvastatin (p less than 0.01). CONCLUSION: Simvastatin offers effective cholesterol lowering for patients with drug resistant familial hypercholesterolaemia. PMID- 1495663 TI - Foodhandling practices of Dunedin caterers: a cause for concern. AB - AIM: Foodhandling practices in the Dunedin catering industry were assessed to determine if they were correct, preventing the transmission of foodborne disease to the public. METHOD: A random sample of 300 foodservice outlets was selected. Information was collected during personal interviews with managers using a prepared questionnaire. Potentially dangerous practices were further analysed and summed to identify "at risk" operations. RESULTS: Response rate was 71%. Thirty six percent of restaurants, 27% of takeaway bars and 25% of deli-bars and butchers could have been considered at risk operations. Few managers had any formal training in preparing and serving food, and less than 20% of managers and personnel had any food hygiene training. CONCLUSIONS: Current legislation and its enforcement is unable to adequately address incorrect food handling practices. It is recommended that revisions of the law emphasise the importance of correct practices and their enforcement. Food hygiene training should become compulsory for all who work in the catering industry. PMID- 1495662 TI - Benzodiazepine use in general practice--is it a problem? AB - AIMS: The aim of this study was to describe benzodiazepine use in a general practice. METHODS: A prevalence study in an Auckland general practice was undertaken to describe the benzodiazepines prescribed, patterns of use and compliance. An associated case control study compared benzodiazepine users and nonusers. RESULTS: The age standardised prevalence rate of benzodiazepine use in this Auckland general practice was 3.4% for patients over 20 years of age. The benzodiazepine users described were predominantly elderly (70% over 60 years of age) and female (62.5%). They had significantly more medical and psychiatric complaints than matched controls. Triazolam and diazepam accounted for 60.9% of the benzodiazepines prescribed. Over one-third of the patients using benzodiazepines were concurrently prescribed other psychotropic medications, primarily tricyclic antidepressants. CONCLUSION: This rate suggests an overall decline in benzodiazepine use since previous studies. Benzodiazepines continue to be prescribed predominantly in the elderly, a group at considerable risk from side effects. Doctors should continue to inform their patients about the side effects of benzodiazepines, the risks of dependence and difficulties of withdrawal. PMID- 1495664 TI - Smokefree medical students. PMID- 1495665 TI - The management of rheumatoid arthritis of recent onset. PMID- 1495666 TI - Look before you leap--your health and the public health. State or market? PMID- 1495667 TI - Screening for noninsulin dependent diabetes mellitus. PMID- 1495668 TI - Annual practising certificate. PMID- 1495669 TI - Baseline risk for asthma deaths. PMID- 1495670 TI - Bed sharing or lung fluid as a cause of cot death? PMID- 1495671 TI - Cervical screening. PMID- 1495672 TI - Cancer inquiry at National Women's Hospital. PMID- 1495673 TI - NSAIDs and peptic ulcer. PMID- 1495674 TI - Prescription charges and drug utilisation. PMID- 1495675 TI - Sexually transmitted diseases 1991. PMID- 1495676 TI - Imaging the adrenal cortex: why and wherefore? PMID- 1495677 TI - The stability of 99Tcm directly labelled to an Fab' antibody via stannous ion and mercaptoethanol reduction. AB - The anti-CEA FO23C5 F(ab')2 antibody was directly radiolabelled with 99mTcm by two methods (stannous ion and mercaptoethanol reduction) and compared in vitro and in vivo for label stability. By both methods, reduction of the F(ab')2 fragment produced primarily Fab' fragments. By both methods, the label was stable to 99Tcm-pertechnetate formation in vitro. Analysis by high performance liquid chromatography (HPLC) of serum, urine, kidney and liver homogenates from mice injected with 99Tcm-antibodies by both methods consistently showed a prominent radiolabelled peak with an estimated molecular weight of about 300 daltons. An identical peak was observed in the analysis of patient samples in a related investigation from this laboratory. Cysteine was radiolabelled with reduced 99Tcm and analysed by HPLC and thin layer chromatography (TLC); one of the 99Tcm cysteine species so produced showed the same chromatographic behaviour as that of the 300 dalton species. In conclusion, the FO23C5 and other antibodies are stably labelled with 99Tcm via either stannous ion or mercaptoethanol reduction. In mice and in patients, the labelled proteins are either catabolized or, more likely, the 99Tcm label is transchelated such that the label is present on several low molecular weight species, the most prominent of which is postulated to be 99Tcm cysteine. PMID- 1495678 TI - A pharmacological guide to medicines which interfere with the biodistribution of radiolabelled meta-iodobenzylguanidine (MIBG). AB - Radiolabelled meta-iodobenzylguanidine (MIBG) is widely used in the diagnosis, follow-up and treatment of patients with tumours of neural crest origin. Some commonly prescribed and readily available over-the-counter medicines interfere with the uptake and biodistribution of this radiopharmaceutical. This may lead to poor concentration of radiolabelled MIBG within the target organs and tissues. The clinical implications are a potentially inaccurate assessment of tumour burden during diagnostic studies and a suboptimal radiation dose when MIBG is employed for targetted radiotherapy. In order to avoid false negative results a comprehensive list of prescribed and over-the-counter medicines that have the potential to inhibit uptake of MIBG has been compiled. It is hoped that this will help nuclear medicine physicians to avoid this pitfall. PMID- 1495679 TI - Single photon emission computed tomography using 99Tcm-HMPAO in Alzheimer's disease. AB - Brain single photon emission computed tomography (SPET) using 99mTcm hexamethylpropyleneamine oxime (HMPAO) was performed in 37 patients satisfying the standard clinical criteria of Alzheimer's disease (AD), correlating results with patient's age of onset, duration of illness, severity of dementia, neuropsychological impairment, computed tomography (CT) and EEG findings. All patients had abnormal SPET: 23 were bilaterally symmetric, 10 were bilaterally asymmetric and four showed unilateral low regional cerebral perfusion. Low perfusion in bilateral parietal regions was the most consistent finding and was present alone or with other abnormal regions in 31 patients (84%). The only significant clinical correlation was found between asymmetric SPET changes and onset of disease before the age of 65 years. Fifty per cent of patients with presenile onset, but only 19% with senile onset had asymmetric low regional cerebral perfusion. Fifteen of the 36 patients had normal brain CT scans, and 9 of 31 patients receiving EEG examination had normal results. Although clinical evaluation is the most valuable diagnostic tool, brain SPET is a sensitive test for physiological investigation in AD. PMID- 1495680 TI - Assessment of tissue viability in frostbite by 99Tcm-HDP scintigraphy: an experimental study in New Zealand white rabbits. AB - Since the appearance of superficial tissue is often an unreliable indicator of deep tissue viability in cases of frostbite, radionuclide scintigraphy with 99Tcm disodium oxidronate (HDP) was used to assess changes in tissue viability after experimental freezing and thawing of the rabbit ear. One shaved ear, left or right, of each of eight New Zealand white rabbits was frozen with a glass bottle (diameter of bottom 2 cm) filled with liquid nitrogen (-180 degrees C) for 5 min under Ketalar-Rompun anesthesia, the other ear serving as a control. Radionuclide scintigraphy was performed by giving a bolus intravenous injection of 130-170 MBq (3.5-4.5 mCi) 99Tcm-HDP. Radionuclide imaging was used to follow the development of the demarcation line. Scintigraphy was performed 2 h after frostbite and then after 24 h, 48 h, 1 week and 3 weeks. The frostbitten area seemed macroscopically to be warm and swollen immediately after the induction of frostbite. Scintigraphy showed the frostbitten area to be much warmer than the surrounding tissue for the first week and it was not until after that the first cold spots appeared in the middle of the frostbitten area. The necrotic and vital tissue could easily be distinguished after 3 weeks. PMID- 1495681 TI - The effect of intracavernosal haemodilution on the radionuclide quantification of penile vascular changes during pharmacologically induced penile erections. AB - Radionuclide phallography was performed using 99Tcm-labelled red blood cells in conjunction with pharmacologically induced penile erections. The radioactivity content of aliquots of systemic venous blood taken from the antecubital vein was compared with aliquots of blood withdrawn from the penile cavernosa 20 min after an intracavernosal injection of 10 micrograms prostaglandin E1. The cavernosal samples showed significantly lower counts per unit of blood compared to the systemic venous blood indicating a comparatively lower concentration of tagged red blood cells. On haematological analysis, a significant difference in the haematocrit of the two samples was also established. The fall in the cavernosal haematocrit was found to result from dilution of the cavernosal blood pool by the injected volume of the drug since larger volumes of injection produced a greater fall in the haematocrit. Restriction of the cavernosal venous outflow in response to the injection of the vasoactive drug causes sequestration of the diluted blood in the cavernosal compartment. This factor might affect the quantification of penile blood volume using radiotracer methods. PMID- 1495682 TI - Difference in inhaled aerosol deposition patterns in the lungs due to three different sized aerosols. AB - Deposition patterns of inhaled aerosol in the lungs were studied in five normal subjects and 20 patients with lung disease by inhaling radioaerosols with three different particle size distributions. These aerosols were generated from BARC, UltraVent, and Mistogen-EN-142. Particle size distributions generated by these three nebulizers were 0.84, 1.04 and 1.93 microns in activity median aerodynamic diameter (AMAD) with its geometric standard deviation (sigma g) of 1.73, 1.71 and 1.52, respectively. Deposition patterns of inhaled aerosols were compared qualitatively and quantitatively by studying six different parameters: alveolar deposition ratio (ALDR), Xmax, Xmean, standard deviation (S.D.), skewness and kurtosis of the radioactive distribution in the lungs following inhalation. It has been found that aerosol deposition patterns varied with particle size. The unevenness of aerosol deposition, Xmax, Xmean and the number of 'hot spots' became more prominent with the increase in particle size, whereas values of ALDR and S.D. decreased as particle size increased. Knowing these deposition characteristics would facilitate a judicious application of aerosol inhalation to medical use. PMID- 1495683 TI - Assessment of an attenuation correction for SPET by means of PET images. AB - The attenuation correction for single photon emission computed tomography (SPET) data developed by Luig et al. was tested with positron emission tomography (PET) data. Since the PET attenuation correction is very precise, it may be used as a reliable measure of the functionality of the SPET correction. It was found that, in the case of homogeneous attenuation and activity distribution, the results of Luig's correction are equivalent to those obtained with the PET correction. Inhomogeneous distributions of activity are corrected satisfactorily as long as the absorption of the medium is sufficiently homogeneous. Inhomogeneous absorption, however, leads to inadequate correction. In the case of sections through the lung, Luig's method might 'correct' the data in the wrong direction. PMID- 1495684 TI - 123I excretion in breast milk--additional data. PMID- 1495685 TI - Radionuclides in the investigation of peripheral vascular disease. PMID- 1495686 TI - A randomized comparison of secondary closure and secondary intention in patients with superficial wound dehiscence. AB - OBJECTIVE: To determine whether secondary closure or secondary intention results differ with respect to time for complete healing and number of postoperative visits in patients with superficial wound dehiscence. METHODS: A randomized trial involved 33 obstetric and gynecologic patients at the University of Mississippi Medical Center who experienced superficial wound dehiscence. Subjects were assigned to secondary-closure or secondary-intention groups. The two groups were similar in age, absolute body weight, percent ideal body weight, length of the primary surgical procedure, estimated blood loss at the primary surgical procedure, portion of the would that opened, preoperative hemoglobin concentration, and preoperative hematocrit. RESULTS: Patients randomized to secondary closure required a mean (+/- standard deviation) of 17.6 +/- 7.2 days from dehiscence to complete healing, whereas those assigned to secondary intention required 61.2 +/- 35.8 days (P less than .001). The secondary-closure group required a mean of 2.0 +/- 0.7 postoperative visits, compared with 8.4 +/- 6.2 visits in the secondary-intention group (P less than .001). CONCLUSION: Secondary closure of superficial wound dehiscence is superior to healing by secondary intention. PMID- 1495687 TI - Hysteroscopic endometrial ablation using the rollerball electrode. AB - OBJECTIVE: To assess the efficacy of hysteroscopic endometrial ablation with the rollerball resectoscope. METHODS: From April 1989 to March 1991, 64 women underwent hysteroscopic endometrial ablation using electrosurgery. Telephone follow-up was obtained for 61 patients at least 6 months after the procedure. The majority of patients requested endometrial ablation because of irregular heavy menses, and two patients presented with postmenopausal bleeding. All patients had preoperative endometrial sampling that demonstrated benign endometrial histology. Five women had previous endometrial ablation with the Nd:YAG laser, with persistent bleeding. Eight patients had endometrial polyps and six had submucous fibroids that were resected at the time of hysteroscopic ablation. RESULTS: The average operative time was 31.6 minutes, and an average of 304 mL of distending medium was absorbed during the procedure. Complications included one uterine perforation in a patient who had a previous Nd:YAG ablation, and one epidural anesthetic complication. At follow-up, 18 women (29.5%) reported amenorrhea, 16 (26.2%) reported spotting, 21 (34.4%) reported decreased menstrual flow, four (6.6%) had no change, and two (3.3%) noted increased flow. Subjectively, 49 patients (80.3%) reported a satisfactory outcome. Of the 12 who were not satisfied, seven underwent a repeat ablation with satisfactory results, four chose hysterectomy, and one elected not to have further therapy. CONCLUSION: Endometrial ablation with the rollerball electrode is a safe, excellent method of management in women with excessive menstrual flow and provides a cost-effective, minimally invasive alternative to hysterectomy. PMID- 1495688 TI - Quantitative and qualitative effects of douche preparations on vaginal microflora. AB - OBJECTIVE: To determine the effect of douching on the quantitative and qualitative makeup of the vaginal microflora. METHODS: We first evaluated the effect of douching with a solution of physiologic saline to determine the effect of washing the vaginal surface. Two douche preparations, one containing 0.04% acetic acid and one containing 0.30% povidone-iodine, were evaluated subsequently to determine whether any effects occurred in addition to those noted with saline. Duplicate vaginal swab samples were obtained at predetermined intervals from ten healthy volunteers for three sampling cycles before and after use of the douche preparations for various periods of time. Samples were analyzed for total facultative and obligately anaerobic bacterial populations. RESULTS: The use of a douche preparation containing acetic acid caused a transient reduction of the total bacterial counts, with most of the change attributable to the effect of washing the surface of the vaginal vault as noted with physiologic saline. In contrast, the povidone-iodine preparation caused a significant reduction in total counts compared with those obtained after use of a physiologic saline solution by the same subjects (P = .02). Little change in the qualitative makeup of the vaginal microflora occurred. CONCLUSION: The use of povidone-iodine douches decreases the numbers of the dominant bacterial species beyond those expected with other douches. In some individuals, such changes may allow rapid proliferation of potential pathogens during this altered state, increasing the risk of associated infections. PMID- 1495689 TI - Treatment of premenstrual syndrome with fluoxetine: a double-blind, placebo controlled, crossover study. AB - OBJECTIVE: Although its etiology is unknown, it has been hypothesized that premenstrual syndrome (PMS) is linked to a deficiency of central serotoninergic activity. In the present study, we evaluated the effect of fluoxetine, a specific serotonin uptake inhibitor, on PMS symptoms. METHODS: Following extensive screening, including several psychological inventories, eight women with severe persistent PMS participated in a 6-month double-blind, placebo-controlled, crossover study which included three months each of daily fluoxetine 20 mg or placebo, administered in a randomized order. Symptoms were evaluated using the Calendar of Premenstrual Experiences and other psychometric measures. RESULTS: Compared with placebo, treatment with fluoxetine was associated with an improvement in PMS symptoms as judged by highly significant decreases in behavioral (P less than .005), physical (P less than .05), and total (P less than .005) Calendar of Premenstrual Experiences scores; Beck Depression Inventory scores (P less than .005); Profile of Mood States subscales scores including depression (P less than .005), tension (P less than .005), and anger (P less than .01); and State-Trait Anxiety Inventory scores. The use of fluoxetine was associated with a greater mean reduction in behavioral (75%) than in physical scores (40%), with a mean decrease in total Calendar of Premenstrual Experiences scores of 62%, which rendered these scores similar to follicular phase values. Thus, the luteal phase symptomatology of PMS was effectively abolished. At this dose, no significant side effects or complications were noted during treatment. CONCLUSION: Fluoxetine appears to be a highly effective, well-tolerated treatment for the psychological and physical symptoms accompanying severe PMS. PMID- 1495690 TI - Chorionic villus sampling: transabdominal versus transcervical approach in more than 4000 cases. AB - OBJECTIVE: To address the evolving trends in the choice of transabdominal or transcervical chorionic villus sampling (CVS) at a teaching hospital and to evaluate the influence of gestational age on the approach chosen. METHODS: We analyzed our CVS data base, which contained information from 1986-1991. The proportions of transabdominal and transcervical CVS were tabulated for each year. In addition, the distribution of the CVS approaches over the various gestational ages was examined. RESULTS: During the study period, 4290 CVS procedures were performed. The rate of the transabdominal technique was stable at about 15% per year except for the first 2 years, when essentially all procedures were transcervical. Use of transabdominal CVS increased with advancing gestational age, from 3.6% at less than 10 weeks' gestation to 97.6% at greater than 14 weeks (chi 2 = 120, P less than .001; r = 0.791). CONCLUSIONS: The choice between the transabdominal and transcervical approach to CVS largely reflects the route emphasized during the physician's training. When choice is based strictly on technical limitations due to placental position, the overall transabdominal CVS rate is approximately 15%. A shift from transcervical to transabdominal CVS occurs with increasing gestational age as the placenta gains bulk and moves away from the cervix. After 14 weeks' gestation, most procedures are performed transabdominally. PMID- 1495691 TI - Accelerated cardiac growth and abnormal cardiac flow in fetuses of type I diabetic mothers. AB - OBJECTIVES: To determine the growth patterns of the fetal heart and the development of cardiac function during gestation in fetuses of diabetic mothers, and to compare these findings with those of normal fetuses. METHODS: Serial M mode and Doppler echocardiographic recordings were made at 4-week intervals in 14 fetuses of well-controlled type I insulin-dependent diabetic mothers and in ten control fetuses at 20-36 weeks' gestation. The following variables were measured: interventricular septal thickness, left ventricular wall thickness, right ventricular wall thickness, ratio between the peak velocities during early passive ventricular filling and active atrial filling at the level of the atrioventricular valves, peak velocities, and time to peak velocity at the level of the ascending aorta and pulmonary artery. RESULTS: In both groups of fetuses, all of the indices increased linearly with gestation. However, fetuses of diabetic mothers showed significant differences in the slope and intercept values for the function describing the growth of the interventricular septum (P less than or equal to .001) and the right and left ventricular wall thicknesses (P less than or equal to .01), resulting in accelerated cardiac growth. The function describing the development of the ratios between early and active ventricular filling showed differences in slope and intercept values at the level of both the mitral (P less than or equal to .001) and tricuspid valves (P less than or equal to .001), resulting in a lower rate of increase during diabetic pregnancy when compared with control fetuses. Significantly higher intercept values were found in the functions describing the increase of peak velocities in the aorta and pulmonary artery in fetuses of diabetic mothers (P less than or equal to .01), whereas the slopes were similar to those of control fetuses. No differences were found in the time to peak values between the groups of fetuses. No relationships were found between the echocardiographic results and the metabolic control of pregnancy or fetal characteristics. CONCLUSIONS: This study suggests that strict maternal diabetes control does not exclude accelerated fetal cardiac growth and abnormal development of cardiac function. PMID- 1495692 TI - Umbilical artery velocimetry in predicting perinatal outcome with intrapartum fetal distress. AB - The aim of this study was to see whether umbilical artery Doppler velocimetry predicts intrapartum fetal distress evidenced by poor perinatal outcome. Umbilical velocimetry was performed on 102 parturients with a presumptive diagnosis of fetal distress based on fetal heart rate (FHR) patterns. A mean systolic-diastolic ratio (S/D) of 3 or more after 30 weeks' gestation was considered abnormal. Poor perinatal outcome was defined by any of the following: small for gestational age, low Apgar score, acidosis, meconium below the vocal cords, prolonged neonatal hospital stay, neonatal intensive care unit admission, and neonatal morbidity. Eighty-two patients had normal S/Ds and 20 had abnormal ratios. Eighteen neonates (90%) in the abnormal-SD group had at least one adverse outcome, compared with only 13 (15.8%) of those with a normal S/D, a statistically significant difference (P less than .001). Umbilical artery S/D used as a screening tool to detect poor perinatal outcome had a sensitivity of 65 100%, specificity of 83-92%, positive predictive value of 20-81%, negative predictive value of 91-100%, and a kappa index of 0.24-0.63. These findings suggest that umbilical artery Doppler velocimetry may be useful as an adjunct in the assessment of intrapartum FHR patterns suggesting fetal distress. PMID- 1495693 TI - Natural history of the minimally abnormal Papanicolaou smear. AB - OBJECTIVE: We sought to determine the natural history of the cytologic and colposcopic changes in patients with minimal abnormalities on their Papanicolaou smears (atypical squamous cells of undetermined significance or low-grade squamous intraepithelial lesion [SIL]). METHODS: Between November 1988 and November 1990, 632 women with abnormal Papanicolaou smears as listed above were evaluated at Los Angeles County-Olive View Medical Center. Each had review of cytology, repeat Papanicolaou smear, and colposcopy of the lower genital tract. We excluded those who were pregnant or had findings demonstrative of moderate dysplasia or worse, or had a cervical biopsy for any other indication. Women with symptomatic vaginal discharge were treated and remained in the study. Subjects were followed every 3 months with repeat Papanicolaou smear and colposcopy for a minimum of 9 months. If at any time the Papanicolaou smear or colposcopy was consistent with moderate dysplasia or worse, directed biopsies and endocervical curettage were performed, and treatment was given accordingly. Two hundred ninety four patients fulfilled all inclusion criteria and had adequate follow-up data. RESULTS: Nine months after enrollment, 42 of 91 women (46.2%) with atypical squamous cells had persistent changes, none had progression, and 49 (53.8%) had regression to normal. In those with low-grade SIL, 37 of 203 cases (18.2%) persisted, seven (3.4%) progressed, and 159 (78.3%) regressed by 9 months. Patients in the first group were more likely to have persistence of the cytologic abnormalities than were those in the second (P less than .01). Only the latter group progressed to high-grade dysplasia during the 9-month study interval. CONCLUSION: The majority of women with confirmed minimal cytologic changes on Papanicolaou smear will have complete colposcopic and cytologic regression over a short interval. PMID- 1495694 TI - Strategies for improving the specificity of screening for ovarian cancer with tumor-associated antigens CA 125, CA 15-3, and TAG 72.3. AB - OBJECTIVE: To assess different strategies for improving the specificity of screening for ovarian cancer with tumor-associated antigens, including concomitant measurement of multiple tumor markers and serial measurement of CA 125. METHODS: A combination of CA 125, CA 15-3, and TAG 72.3 was evaluated in serum samples from 217 of 1010 apparently healthy postmenopausal women who had participated in a study of screening for ovarian cancer and who had a serum CA 125 level of 20 U/mL or greater. In addition, serial serum CA 125 levels were determined in 30 women with an initially elevated CA 125 level (30 U/mL or more) and 30 women with a CA 125 level less than 30 U/mL. RESULTS: The specificity of CA 125 at upper limits of 30 and 50 U/mL was increased from 97.0 and 99.5%, respectively, to 98.9 and 99.9% when a positive test was defined as an elevated serum CA 125 level in combination with either a CA 15-3 greater than 30 U/mL or a TAG 72.3 greater than 10 U/mL. Definition of a positive result as a serum CA 125 level greater than 50 U/mL at the initial test and greater than 30 U/mL at 3 month follow-up achieved a specificity of 99.6%. CONCLUSION: Levels of specificity suitable for screening asymptomatic postmenopausal women can be achieved using tumor-associated antigens measured serially or in combination. Further studies are required to determine the sensitivity of these strategies for preclinical ovarian cancer. PMID- 1495695 TI - The relationship between breast cancer survival and prior postmenopausal estrogen use. AB - The growth of breast cancer may be mediated by endogenous or exogenous sex steroid hormones, particularly estrogen. However, neither contraceptive nor noncontraceptive estrogen use has been associated definitively with an increased risk of developing breast cancer. In this study, we addressed a corollary question: If a postmenopausal woman develops carcinoma of the breast, is her survival affected by previous use of replacement estrogen? Two hundred fifty-six postmenopausal women with breast cancer entered our Tumor Registry between 1972 1981, inclusive. Of these, 174 took no replacement estrogen before the diagnosis (never-users), 21 had used estrogen previously (past users), and 61 were taking estrogen at the time of diagnosis (current users). Survival analysis revealed a median survival of less than 84 months after diagnosis for never- and past users and greater than 143 months for current users, but these differences were not significant when controlled for stage of disease at diagnosis. We conclude that prior postmenopausal estrogen replacement therapy does not compromise survival in women who subsequently develop carcinoma of the breast. PMID- 1495696 TI - Interleukin-1 inhibits growth of normal human endometrial stromal cells. AB - OBJECTIVE: To understand growth regulation of the endometrium by studying the effect of interleukin-1 beta (IL-1) on human endometrial stromal cell proliferation in vitro. METHODS: Endometrial stromal cells from human endometrium were separated and purified and placed in culture. Fresh and first- and sixth passage cells were incubated with IL-1 (0.025, 0.25, and 2.5 ng/mL) for 24, 48, and 72 hours, respectively. Proliferation as a function of DNA synthesis was assessed by measuring 3H-thymidine incorporation. Experiments were then repeated in the presence of indomethacin to determine whether IL-1 effects were dependent upon prostaglandin synthesis. We evaluated overall growth by adding IL-1 to cell cultures of sixth-passage stromal cells every 3 days and by performing cell count studies. RESULTS: Interleukin-1 beta significantly inhibited 3H-thymidine uptake in freshly explanted endometrial stromal cells at all doses in a dose-dependent manner; a 44% inhibition was seen at 2.5 ng/mL IL-1 after 72 hours of incubation. In first- and sixth-passage cells, 3H-thymidine uptake was inhibited only at intermediate and high doses of IL-1. Cell count studies showed that sixth-passage cells were significantly inhibited by IL-1 after 23 days of growth (22%; P less than .01). Adding indomethacin did not affect inhibition of growth. CONCLUSION: Interleukin-1 beta inhibits growth of normal human endometrial stromal cells in vitro and does not appear to be mediated by arachidonic acid metabolites. This inhibition of growth may be important for maintenance of a normal endometrial phenotype. PMID- 1495697 TI - Immunohistochemical localization of inhibin/activin subunits in human placenta. AB - OBJECTIVE: To examine the cellular localization of each inhibin subunit in human placenta throughout pregnancy. METHOD: Placental tissues were collected and fixed in Bouin's solution, and studied with the immunohistochemical technique avidin biotin-peroxidase complex. RESULTS: There was immunohistochemical staining with antisera against each inhibin subunit in the syncytiotrophoblast, but not in the cytotrophoblast. In the first-trimester placenta, positive immunostaining for alpha- and beta A-subunits was clearly observed in the syncytial layer of villi, whereas staining for beta B-subunit was faint. In the second-trimester placenta, the relative intensities of staining for alpha- and beta A-subunits were similar to those in the first-trimester placenta, and enhanced positive immunostaining with beta B-subunit antiserum was observed. The relative amount of immunostainable alpha-subunit declined within the syncytiotrophoblast of the third-trimester placenta, whereas levels of immunostainable beta-subunits were unchanged. CONCLUSIONS: Inhibin subunits may be produced in the syncytiotrophoblast throughout pregnancy, and activin as well as inhibin may be synthesized in the syncytiotrophoblast of the term placenta. PMID- 1495699 TI - Risks associated with pregnancy in spinal cord-injured women. AB - We reviewed the experience with pregnancy in spinal cord-injured women at the University of Washington over the past 10 years. During that time, 11 women with spinal cord injury had 13 pregnancies. Infant outcome was uniformly good. No major obstetric complication occurred. The mothers experienced medical problems including urinary tract infection in ten and pyelonephritis in three. Autonomic hyperreflexia occurred in three of five subjects with lesions at or above the sixth thoracic vertebra. Pregnancy in the spinal cord-injured patient involves medical risk for the mother, but with careful management, an excellent outcome for both mother and infant may be anticipated. PMID- 1495698 TI - Quadruplet pregnancy: contemporary management and outcome. AB - Quadruplets are occurring more frequently as assisted-reproduction techniques improve fertility in couples previously unable to conceive. Ten quadruplet pregnancies cared for in one perinatal practice over 5 years had excellent outcome. The mean gestational age at delivery was 32.5 weeks, compared with approximately 30 weeks in the literature. There were no perinatal deaths and no long-term morbidity. Our patients were compared with a series of 57 consecutive patients with quadruplet pregnancies monitored by a home monitoring system. Parity of 1 or more appeared to improve outcome. Pregnancy-induced hypertension occurred in nine of our pregnancies and necessitated delivery in seven instances. Fetal distress was responsible for two deliveries and uncontrollable preterm labor for only one. Key points in our management protocol include prophylactic use of low-dose aspirin, home contraction monitoring, use of terbutaline pump tocolysis, and bed rest at home starting at 16 weeks. PMID- 1495700 TI - Pregnancy outcome following exposure to angiotensin-converting enzyme inhibitors. AB - OBJECTIVE: Case reports of suspected adverse pregnancy outcomes associated with prenatal exposure to angiotensin-converting enzyme inhibitors, particularly oligohydramnios, prolonged neonatal anuria, and defects of ossification of the skull dome, prompted us to examine pregnancy outcome in a large cohort of pregnant women for whom complete drug exposure information was known. METHODS: We studied the prescribed drug exposure histories and pregnancy outcomes of all women aged 15-44 years enrolled in Tennessee Medicaid who delivered a live-born or stillborn infant between January 1, 1983 and December 31, 1988. RESULTS: Of the 106,813 women enrolled in Tennessee Medicaid who delivered either a live-born or stillborn infant during the study period, 19 were exposed to an angiotensin converting enzyme inhibitor during pregnancy. All 19 women delivered live infants. Among the 19 newborns, one preterm infant had prolonged anuria necessitating dialysis and a second preterm infant had microcephaly and a large occipital encephalocele. CONCLUSIONS: These outcomes represent a systematic follow-up of all angiotensin-converting enzyme inhibitor-exposed pregnancies. Despite the small number of exposures, there were two outcomes previously linked to prenatal use of these drugs, suggesting that the absolute risk may be high. In light of these findings and the case reports of others, it is prudent to avoid the use of angiotensin-converting enzyme inhibitors in pregnancy. PMID- 1495701 TI - Antenatal treatment of fetal alloimmune thrombocytopenia. AB - OBJECTIVE: To review our experience with, and to evaluate the efficacy of, antenatal pharmacologic treatment of pregnancies complicated by alloimmune thrombocytopenia. METHODS: We reviewed the records of six pregnancies complicated by alloimmune thrombocytopenia recently cared for at the University of Iowa Fetal Diagnosis and Treatment Unit. All patients had a history consistent with alloimmune thrombocytopenia in a previous gestation. All fetuses had thrombocytopenia on funipuncture at 20-32 weeks' gestation, and all patients and fetuses demonstrated a platelet antigen incompatibility. Three women initially received weekly gamma globulin infusions, two received gamma globulin and dexamethasone, and one had no initial treatment but was given gamma globulin and dexamethasone at 32 weeks' gestation. Repeat funipuncture was performed at 3.5- to 7-week intervals, and therapeutic modifications were made as necessary. RESULTS: In five cases, the last funipuncture before delivery documented platelet counts adequate for vaginal delivery. One woman, who received gamma globulin alone with good initial response, was delivered by cesarean for a platelet count of 25,000/microL at 39 weeks. Following delivery, all infants were thoroughly evaluated, and none had evidence of intracranial hemorrhage or other alloimmune thrombocytopenia-associated morbidity. All had normal platelet counts at discharge from the hospital. CONCLUSIONS: Our experience confirms the efficacy of gamma globulin treatment, but indicates that not all fetuses will respond to it alone. Serial funipunctures are essential to evaluate patient response and allow appropriate therapeutic modifications. Randomized studies are needed to determine the optimal antenatal pharmacologic therapy for this disease. PMID- 1495702 TI - A comparison of pre-discharge survival and morbidity in singleton and twin very low birth weight infants. AB - The perinatal mortality rate of twins is four to 11 times higher than that of singletons, and twins are widely reported to have more morbidity than singletons, mainly because of a higher preterm birth rate. However, it is not clear that live born preterm birth rate. However, it is not clear that live-born preterm twins suffer greater morbidity than comparable singletons. In fact, twins have been reported to develop pulmonary maturity earlier than singletons, which might result in decreased morbidity relative to comparable preterm singletons. We conducted this retrospective review of 496 consecutive singleton and 104 twin infants weighing 500-1499 g and born alive at 24-31 weeks' gestation to determine whether pre-discharge survival and morbidity in very low birth weight (VLBW) twin infants were greater than those of comparable singletons. The mean (+/- standard deviation) gestational age of the singletons was 27.5 +/- 2.0 weeks and of the twins 27.6 +/- 2.0 weeks. There were no differences in mean gestational age, gestational age distribution, mean birth weight, birth weight distribution, gender, or maternal race between the two groups. The pre-discharge survival rate for twins (77%) was not significantly different than that of singletons (82%). There were no differences between twins and singletons in the incidences of neonatal respiratory distress syndrome (63 versus 71%), pulmonary interstitial emphysema (14 versus 16%), patent ductus arteriosus (28 versus 29%), necrotizing enterocolitis (3 versus 5%), intraventricular hemorrhage (11 versus 16%), and retinopathy of prematurity (11 versus 18%). The incidence of bronchopulmonary dysplasia was significantly less in twins (27 versus 46%; P = .001).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1495703 TI - Prostaglandin D2 production by term human decidua: cellular origins defined using flow cytometry. AB - OBJECTIVE: To measure prostaglandin (PG) D2 output by human decidua at term and to identify the cell population(s) responsible for its production. METHODS: Decidual cell suspensions were prepared enzymatically and the cells were labeled with either of two monoclonal antibodies: F10/89/4, which recognizes the leukocyte common antigen (CD45), or L243, which labels HLA-DR and is specific for macrophages in this tissue. Cells were sorted on a Coulter EPICS 541 flow cytometer. Prostaglandin levels were measured by radioimmunoassay. RESULTS: Human decidua is an important intrauterine source of PGD2 at term. Twenty-nine percent (median) of decidual cells were CD45-positive and 12% were HLA-DR-positive; sorted cell populations were 95% pure. Prostaglandin D2 output (fmol/10(6) cells per 3 hours) by bone marrow-derived (CD45-positive) cells was significantly higher than that by non-bone marrow-derived cells: median 63 (range 35-67) versus 20 (13-21), respectively; HLA-DR-positive cells (macrophages) had the highest PGD2 production rate (186, range 97-288 fmol/10(6) cells per 3 hours). Under basal conditions, PGD2 production by unsorted term decidual cells was not influenced by labor. CONCLUSION: Bone marrow-derived cells (macrophages) are the major source of decidual PGD2 at term. Further studies are required to investigate the possible role of PG production by human decidual macrophages in the mechanism of term and/or preterm labor. PMID- 1495704 TI - Unscheduled hospital admission following ambulatory gynecologic surgery. AB - OBJECTIVE: To identify causes of unscheduled admission following ambulatory gynecologic surgery. METHODS: We compared each patient admitted on an unscheduled basis with two patients who did not require admission. Thirty demographic and clinical factors were evaluated by univariate analysis. Significant factors (P less than .05) were then analyzed using multivariate stepwise logistic regression. RESULTS: During a 4-year period, 90 patients required unscheduled admission. This represented 3.64% of 2470 patients who underwent ambulatory gynecologic surgery. Factors associated with admission by multivariate analysis included: 1) previous abdominal surgery, 2) significant medical illnesses, 3) preoperative hemoglobin concentration, 4) general anesthesia, 5) procedure length, and 6) blood loss. Sensitivity was 60.0%, specificity was 90.6%, and the overall correct rate of prediction was 80.4%. Postoperative emesis, the most common reason for unscheduled admissions, occurred in 23.4% of patients. CONCLUSIONS: Previous abdominal surgery and significant medical illnesses are factors that cannot be altered preoperatively. The need for general anesthesia, procedure length, and blood loss are functions of the procedure and cannot be easily modified. Postoperative emesis may warrant further investigation. Successful antiemetic therapy may reduce unscheduled admissions. PMID- 1495705 TI - Fetal fibronectin: a method for detecting the presence of amniotic fluid. AB - OBJECTIVE: To determine whether fetal fibronectin is a sensitive test for the detection of amniotic fluid (AF) in women with rupture of the membranes. METHODS: In a multicenter clinical trial, pooling, ferning, and nitrazine tests were compared with fetal fibronectin in 339 women at term (study group) with a clinical history of rupture of the membranes and in 67 women at term receiving routine prenatal care (controls). Ruptured membranes was diagnosed if any two of the standard tests were positive. Fetal fibronectin in the cervicovaginal secretions was determined using a qualitative enzyme-linked immunosorbent assay test. Fetal fibronectin was considered positive at 50 ng/mL. RESULTS: The sensitivity of fetal fibronectin in the women with ruptured membranes was 98.2%. No controls had ruptured membranes based on standard test results, but 13 women had fetal fibronectin present. The mean (+/- standard error) interval between sampling and delivery was significantly less in the women positive for fetal fibronectin (169.3 +/- 45.8 hours) than in those with no detectable fetal fibronectin (333.4 +/- 29.0 hours). CONCLUSION: Fetal fibronectin is a sensitive test for detection of AF in the vagina and compares favorably to standard tests. Its low specificity suggests that the assay may detect an alteration in membrane integrity. In addition, in patients without rupture of the membranes, the interval between sampling and delivery is significantly shorter if fetal fibronectin is present. We speculate that the presence of fetal fibronectin in cervicovaginal secretions may be a marker for impending labor in gravidas without gross rupture of the membranes. PMID- 1495706 TI - The association of menstrual cycle, pregnancy, and menopause with recurrent oral aphthous stomatitis: a review and critique. AB - OBJECTIVE: To examine critically the postulated associations between recurrent aphthous stomatitis and the menstrual cycle, pregnancy, and menopause, and to determine why such associations had been accepted previously in the absence of convincing evidence. DATA SOURCES: We used MEDLINE data base searches in 1988 and 1991 to identify all articles since 1966 referring to estrogen, progesterone, menstruation, menstrual cycle, menopause, or pregnancy, and to aphthous stomatitis. Similar searches were carried out in the Index to Dental Literature for the period 1942-1991, and in MEDLINE on CD-ROM in 1991. Articles uncovered were examined for further appropriate references in the 50-year period 1942-1991. We excluded letters, abstracts, and articles in journals that are not peer reviewed. METHODS OF STUDY SELECTION: We discovered one retrospective study on aphthous ulceration and ovarian hormones, eight prospective studies, three uncontrolled trials on the use of hormones in aphthous stomatitis, one controlled trial, and four review papers. DATA EXTRACTION AND SYNTHESIS: Each paper was carefully read, in translation where necessary, and opinions and findings were critically examined for source, authenticity, and statistical analysis. Each paper was also examined critically in terms of its review and acceptance of previous papers. The papers were too diverse in nature to permit a structured criticism. CONCLUSIONS: No associations have been established between aphthous stomatitis and the premenstrual period, pregnancy, or menopause. No properly designed study has shown a therapeutic effect of ovarian hormones on aphthous stomatitis. Reasons for this lack and the need for large-scale studies are identified. PMID- 1495708 TI - Functional ovarian cysts in relation to the use of monophasic and triphasic oral contraceptives. PMID- 1495707 TI - Perinatal transmission of human immunodeficiency virus-1 infection and maternal immunization strategies for prevention. AB - OBJECTIVES: To review the current understanding of the epidemiologic and pathogenetic features of human immunodeficiency virus-1 (HIV-1) infection in pregnancy and perinatal HIV infection, and to explore immunization strategies for preventing maternal-infant transmission of HIV. DATA SOURCES: MEDLINE data base and reference lists of articles were used to identify relevant papers. Reports from conferences were noted if the data had not yet been published. METHODS OF STUDY SELECTION: We reviewed all English-language papers pertaining to maternal or fetal infection with HIV, immunology of HIV infection, immunization of pregnant women, or immunization against HIV. DATA EXTRACTION AND SYNTHESIS: Human immunodeficiency virus infection of women is increasing, and vertical transmission of HIV to children is a growing problem. There is evidence for intrauterine, intrapartum, and immediate postpartum transmission, but it is thought that the majority of transmissions occur peripartum by a minor subset of the maternal HIV-1 strains. Diagnostic advances include measurement of HIV specific immunoglobulin A (IgA) and improved systems for polymerase chain reaction and virus isolation from potentially infected infants. Clinical and immunologic correlates of transmission remain uncertain. CONCLUSIONS: The epidemiology of transmission must be determined in more diverse populations. The timing and pathogenesis of HIV transmission from infected mother to fetus require better description, and improved diagnostic tools are needed. Immunologic and mechanical determinants that prevent transmission in the majority of cases need to be identified more precisely. Clinical trials to evaluate active immunization of HIV-infected pregnant women with candidate AIDS vaccines will potentially help answer many of these questions. PMID- 1495709 TI - Prospective risk of stillbirth. PMID- 1495710 TI - Routine hysterectomy for large asymptomatic uterine leiomyomata: a reappraisal. PMID- 1495711 TI - Routine hysterectomy for large asymptomatic uterine leiomyomata: a reappraisal. PMID- 1495712 TI - Adenosine in the treatment of maternal paroxysmal supraventricular tachycardia. AB - Paroxysmal supraventricular tachycardia is the most common sustained cardiac arrhythmia in pregnant women. Because nearly 50% of these supraventricular tachyarrhythmias fail to respond to vagal maneuvers, other therapies are used, including electrocardioversion and pharmacologic agents. Propranolol, verapamil, and adenosine have Food and Drug Administration-approved labeling for acute termination of supraventricular tachycardia. Verapamil has been the most commonly used agent in the general population but it has several shortcomings, such as its potential to cause or exacerbate systemic hypotension, congestive heart failure, bradyarrhythmias, and ventricular fibrillation. In addition, verapamil readily crosses the placenta and has been shown to cause fetal bradycardia, heart block, depression of contractility, and hypotension. Adenosine has several advantages over verapamil, including rapid onset, brevity of side effects, theoretical safety, and probable lack of placental transfer. Adenosine ultimately may prove to be the preferred agent for termination of paroxysmal supraventricular tachycardia in the gravid woman. PMID- 1495713 TI - Termination of supraventricular tachycardia with intravenous adenosine in a pregnant woman with Wolff-Parkinson-White syndrome. AB - BACKGROUND: Pregnancy is associated with an increased frequency of arrhythmias in women with Wolff-Parkinson-White syndrome. We describe the use of intravenous (IV) adenosine for the acute termination of a narrow complex tachycardia in a pregnant patient with this syndrome. CASE: A 26-year-old woman with known Wolff Parkinson-White syndrome presented with dizziness, palpitations, and a narrow complex supraventricular tachycardia. We used IV adenosine to convert the arrhythmia to a normal sinus rhythm. During labor, the patient again developed a narrow complex supraventricular tachycardia, and fetal monitoring revealed recurrent deep variable decelerations. Intravenous adenosine resulted in conversion to sinus rhythm and restoration of the fetal heart rate to normal. Cesarean delivery produced a healthy male infant. CONCLUSIONS: Adenosine is effective in rapidly terminating maternal narrow complex tachyarrhythmias before and during delivery in women with Wolff-Parkinson-White syndrome. It can also treat fetal bradycardia resulting from the maternal arrhythmia. PMID- 1495714 TI - Hypoplastic pulmonary artery: an unusual entity mimicking pulmonary embolism during pregnancy. AB - Hypoplastic pulmonary artery is an unusual congenital malformation. We describe a case of hypoplastic pulmonary artery diagnosed during the third trimester of pregnancy. The clinical and radiologic features mimicked pulmonary embolism, including hemoptysis, chest pain, pleural effusion, mild hypoxemia, and a suggestive ventilation-perfusion scan. Accurate differentiation of this entity from pulmonary embolism is necessary to obviate the need for prolonged anticoagulation. PMID- 1495715 TI - Erythropoietin in pregnancies complicated by severe anemia of renal failure. AB - BACKGROUND: Recombinant human erythropoietin has been approved for treatment of the anemia of renal failure since 1989, yet data regarding the safety and efficacy of this drug in pregnancy are limited. We used recombinant human erythropoietin to treat the anemia of renal disease in three pregnant women. CASES: Nadir hematocrit values before initiation of erythropoietin were 19-23%. Erythropoietin, 50-160 U/kg/week subcutaneously, was begun at 14-26 weeks' gestation. Initially, the rise in hematocrit averaged 0.6-2% each week, with peak values of 26.7-32%. Iron supplementation was given simultaneously. Maternal and neonatal outcomes were favorable despite the development of preeclampsia or worsening renal function requiring early delivery. CONCLUSION: In this small series, erythropoietin begun during the second trimester in a dose of about 100 U/kg/week, in conjunction with orally administered iron, appeared to be effective in treating the anemia of renal failure during pregnancy. Additional experience is needed to evaluate the safety of this medication during pregnancy. PMID- 1495716 TI - Acute uric acid nephropathy in pregnancy. AB - BACKGROUND: Although uric acid clearance increases during gestation, uric acid nephropathy is a rare cause of acute renal failure in the pregnant woman. CASE: A 38-year-old woman experienced acute renal failure due to acute uric acid nephropathy at 30 weeks' gestation. The diagnosis was based on extreme hyperuricemia and an elevated uric acid-creatinine ratio. Treatment with forced diuresis, urine alkalinization, and mannitol infusion resulted in a prompt and complete recovery of renal function. The woman ultimately gave birth to a healthy child. CONCLUSION: Acute uric acid nephropathy during pregnancy responds to conventional medical therapy. PMID- 1495717 TI - Post-miscarriage thyroid dysfunction. AB - BACKGROUND: Thyroid dysfunction is a common postpartum event affecting as many as 16.7% of women. The purpose of this paper was to report the first known case of post-miscarriage thyroid dysfunction. CASE: A 32-year-old woman with a 9-year history of infertility underwent in vitro fertilization. After two spontaneous miscarriages, she delivered a full-term healthy child. Spontaneous menses did not return following delivery, and hormonal evaluation revealed severe postpartum thyroid disease associated with hyperprolactinemia. Retrospective analysis of frozen sera revealed thyroid dysfunction and hyperprolactinemia after the first miscarriage, even though the gestation lasted only 47 days. CONCLUSION: The present case of thyroid dysfunction following a first-trimester miscarriage raises issues concerning the immunology of pregnancy and thyroid dysfunction after pregnancy. The incidence of post-miscarriage thyroid dysfunction and severe postpartum thyroid disease resulting in amenorrhea requires further study. PMID- 1495718 TI - Successful pregnancy outcome in a patient with congenital biliary atresia. AB - Congenital biliary atresia is one of the most common congenital anomalies of the biliary tree. Without surgical correction, two-thirds of all cases of extrahepatic biliary atresia are fatal within 18 months. Historically, the preferred surgical procedure to correct this anomaly has been the Kasai procedure. Surgical treatment of congenital biliary atresia is associated with substantial perioperative morbidity and mortality, as well as long-term sequelae. Portal hypertension and hypersplenism can complicate the course of up to 50% of patients who survive for more than 2 years. Not surprisingly, few of these patients reach adulthood. We report the case of a woman with congenital biliary atresia surgically corrected with the Kasai operation who subsequently reached adulthood and became pregnant. Despite a prenatal course complicated by portal hypertension, bleeding esophageal varices, and hypersplenism, the woman delivered a healthy infant at 36.5 weeks' gestation. PMID- 1495719 TI - Axillary vein thrombosis during pregnancy: a case report. AB - A 32-year-old multiparous woman had progressive swelling of the right arm at 32 weeks' gestation, accompanied by cyanosis and a preserved radial pulse. Phlebography demonstrated a 5-cm thrombus in the axillary vein. No known etiologic factors were found. Intravenous heparin administration resulted in rapid resolution of the clinical findings. Subcutaneous heparin 10,000 U/day was administered for secondary prophylaxis until cesarean at 39 weeks, during which a full dose was administered without complications. Axillary vein thrombosis during pregnancy may be diagnosed by either phlebography or duplex scanning, and preferably should be treated by heparin. Thrombolytic therapy is justified mainly for life-threatening complications such as pulmonary embolism. PMID- 1495720 TI - Fetal stroke associated with elevated maternal anticardiolipin antibodies. AB - Middle cerebral artery infarction explains some cases of congenital hemiparesis with or without neonatal stroke. The etiology of the stroke is often obscure. We describe two infants with imaging evidence of middle cerebral artery infarction whose mothers had elevated anticardiolipin antibody levels after delivery. We speculate that these antibodies may have been responsible for intrauterine thromboembolic stroke. PMID- 1495721 TI - Acute iron intoxication in pregnancy: case report and review of the literature. AB - Limited reports exist regarding acute iron intoxication during pregnancy. The maternal and fetal effects of accidental or deliberate ingestion of large amounts of iron may be catastrophic. A case report of acute iron intoxication, management strategies, and a review of the literature are presented. The cornerstones of effective therapy are aggressive management with emesis induction or gastric lavage, bicarbonate instillation, vigorous intravenous hydration, and chelation therapy with deferoxamine. PMID- 1495722 TI - An unusual complication in a gravida with factor IX deficiency: case report with review of the literature. AB - Factor IX deficiency (hemophilia B, Christmas disease) is an X-linked recessive coagulation disorder. It occurs in one out of every 25,000-30,000 male births and requires even rarer genetic circumstances for phenotypic expression in females. We report the occurrence of a large, late-trimester subchorionic hematoma in a gravida with factor IX deficiency and with laboratory evidence of consumptive coagulopathy during treatment. The patient was managed conservatively and had a successful outcome at term. The only four reported cases of antepartum management of factor IX deficiency in the English literature are reviewed. PMID- 1495723 TI - Antepartum diagnosis of placenta previa percreta by magnetic resonance imaging. AB - BACKGROUND: Placenta previa percreta is a rare but highly morbid condition usually diagnosed intraoperatively. Placental manipulation results in severe bleeding. Magnetic resonance imaging (MRI) might allow antepartum diagnosis of this condition. CASE: A multiparous woman with five previous abdominal deliveries had complete placenta previa diagnosed at 16 weeks' gestation. Bleeding ensured at 29 weeks and she was managed with bed rest. Before planned abdominal delivery, MRI was performed and placenta percreta was diagnosed, which allowed her physician to avoid placental manipulation. Hysterectomy was accomplished with an estimated blood loss of only 2000 mL. CONCLUSION: Antepartum diagnosis of placenta previa percreta by MRI altered the usual diagnostic and surgical approach, diminishing blood loss and morbidity. PMID- 1495724 TI - Transvaginal color Doppler sonography in the prenatal diagnosis of placenta accreta. AB - In a case of placenta accreta diagnosed antepartum, the sonographic findings included absence of the normal retroplacental clear space and presence of multiple dilated blood vessels beneath the placenta. Transvaginal color Doppler sonography was particularly useful in identifying these features. PMID- 1495725 TI - Delivery through the maternal bladder during trial of labor. AB - BACKGROUND: The safety of trial of labor after cesarean has been documented by numerous studies. Large series have demonstrated that in a properly chosen setting, 75% of women can achieve vaginal delivery without undue risk to the mother or fetus. In a small percentage of cases, trial of labor deviates from the expected outcome. CASES: Two infants were delivered through the maternal bladder, one after uterine dehiscence and the other after vaginal rupture at trial of labor. CONCLUSION: Standard and unique complications are reported with trial of labor. Because these complications occur infrequently, they should not discourage an attempt at vaginal delivery after cesarean. PMID- 1495726 TI - Abdominal rescue after failed cephalic replacement. AB - BACKGROUND: Since the introduction of cephalic replacement for shoulder dystocia, the management of failures has not been addressed. The purpose of this report is to describe abdominal hysterotomy as an alternative approach to the resolution of shoulder dystocia. CASE: A 21-year-old woman, gravida 1, experienced severe shoulder dystocia following partial delivery of a 4320-g infant. Classical maneuvers as well as cephalic replacement were unsuccessful before and after general anesthesia. A low transverse hysterotomy permitted manual rotation of the anterior shoulder to the oblique diameter and further descent of the posterior shoulder. Delivery of the posterior arm was then completed without difficulty. CONCLUSION: Persistent failed cephalic replacement, especially after general anesthesia, can be successfully resolved with a hysterotomy using a low transverse uterine incision. PMID- 1495727 TI - First-trimester diagnosed cervico-isthmic pregnancy resulting in term delivery. AB - A 30-year-old multiparous woman at 5.5 weeks' gestation was diagnosed by ultrasound to have a cervical pregnancy. She refused termination because of religious beliefs. After expectant management until 38 weeks' gestation, she delivered a viable infant by cesarean, followed by immediate hysterectomy. Pathologic examination verified cervico-isthmic implantation as well as placenta percreta. PMID- 1495728 TI - Methotrexate pneumonitis in nonsurgical treatment of ectopic pregnancy. AB - We describe a case of pneumonitis following local administration of methotrexate for nonsurgical termination of an ectopic pregnancy. The signs and symptoms were similar to those seen with systemic use of the drug for other ailments. We believe that methotrexate represents a relatively effective alternative to surgery in patients with early unruptured tubal pregnancy, but suggest that it be used with caution in view of possible systemic toxicity. PMID- 1495729 TI - Criminal prosecution for prenatal injury. PMID- 1495730 TI - Umbilical artery aneurysm: prenatal diagnosis and management. AB - BACKGROUND: An umbilical artery aneurysm is an extremely rare lesion. The purpose of this report is to describe the prenatal sonographic characteristics of such a lesion and potential obstetric complications. CASE: A 26-year-old woman, gravida 2, para 1, at 30 weeks' gestation was referred for an ultrasound examination because of "an abnormality of the umbilical cord." An ellipsoid cystic lesion was noted in a single umbilical artery. Doppler and color flow Doppler examinations demonstrated nonpulsatile and turbulent blood flow within the lesion, consistent with a diagnosis of umbilical artery aneurysm. The aneurysm increased in size over time with a progressive decrease in amniotic fluid volume. Despite reassuring bi-weekly antenatal testing and planned delivery by 36 weeks' gestation, the fetus died in utero, probably because of acute umbilical venous compression by the aneurysm. Autopsy confirmed the presence of a large calcified aneurysm of a single umbilical artery. Dissection of the aneurysm demonstrated anatomical patency of the entire artery. The umbilical vein was histologically normal, as were sections of the artery. CONCLUSION: Although extremely rare, an umbilical artery aneurysm is a potentially lethal anomaly. We recommend delivery as soon as fetal lung maturity is assured when this diagnosis is made prenatally. PMID- 1495732 TI - The perinatal management of severe laryngeal stenosis. AB - BACKGROUND: Conditions that completely occlude the fetal larynx are rare. We describe the perinatal course of an infant with severe congenital subglottic stenosis, for whom the prenatal recognition of airway occlusion led to enhanced neonatal management. CASE: Serial ultrasound examinations from 23-37 weeks' gestation led to the diagnosis of upper airway obstruction in the fetus of a 29 year-old woman. Significant findings included fetal ascites, echogenic enlarged lungs, and a dilated fluid-filled trachea. The infant was delivered in a level III hospital with a neonatologist and anesthesiologist in attendance. The cord was not clamped until a tracheostomy was secured. CONCLUSION: Upper-airway obstruction can be diagnosed prenatally by the presence of secondary manifestations. Infant survival may depend on foreknowledge of the pathology and prompt, directed efforts at bypassing the airway obstruction. PMID- 1495731 TI - Fetal ascitic fluid: a new source of lymphocytes for rapid chromosomal analysis. AB - BACKGROUND: The cells found in ascites can be processed like amniotic fluid for fetal karyotyping. We have characterized these cells and used them for a rapid cytogenetic result. CASES: Three patients presented with massive fetal ascites detected by sonography. Samples of ascitic fluid were obtained at fetal paracentesis. Cells from the fluid were cultured using standard methods for fetal blood, and were compared with fetal blood lymphocytes and amniocytes. The length of time in culture, chromosome morphology, and mitotic index of ascitic fluid cells were equivalent to those of fetal blood. In the third case, we performed immunophenotyping on the ascitic fluid cells. CONCLUSION: Ascitic fluid contains lymphocytes that permit rapid chromosomal analysis within 96 hours. PMID- 1495733 TI - Hysteroscopic resection of fibroid with thermal injury to sigmoid. AB - BACKGROUND: Hysteroscopy is being used increasingly, especially as a means of performing uterine surgery. Uterine perforation is the most frequent complication of hysteroscopy. CASE: A 31-year-old woman sustained uterine perforation with a resectoscope during hysteroscopic resection of a pedunculated myoma. The perforation was identified laparoscopically, but laparotomy was necessary to assess the pelvic viscera fully. Perforation of the sigmoid was discovered and the defect was repaired primarily. CONCLUSION: Laparoscopy may be insufficient to evaluate fully the possible sequelae of uterine perforation. Penetrating thermal injury to the colon can be managed successfully with primary repair. PMID- 1495734 TI - Ureteroscopy: a new asset in the management of postoperative ureterovaginal fistulas. AB - Iatrogenic ureteral injury, an uncommon entity, is primarily caused by complications of gynecologic surgery. This report describes a case of ureterovaginal fistula discovered 13 days after a vaginal hysterectomy. Ureteroscopy was performed, with passage of an indwelling ureteral stent for 6 weeks. The patient immediately became continent of urine and the fistula healed, thus avoiding the need for further surgery. PMID- 1495735 TI - Enterobius vermicularis salpingitis: a distant episode from precipitating appendicitis. AB - Chronic pelvic inflammatory disease is a common gynecologic diagnosis in women with chronic pelvic pain. When standard antimicrobial therapy does not improve the clinical status, uncommon diagnoses such as Enterobius vermicularis should be considered. In this case, E vermicularis presented as acute and chronic salpingitis in a patient who had had E vermicularis-related appendicitis 5 years earlier. PMID- 1495736 TI - Percutaneous catheter drainage of tubo-ovarian abscesses. AB - We present the successful treatment of tubo-ovarian abscesses in three young patients by continuous percutaneous drainage, inserted under the guidance of real time ultrasonography using only local anesthesia. Each patient had been diagnosed laparoscopically as suffering from acute pelvic inflammatory disease, but had formed abscesses despite extensive broad-spectrum antibiotic therapy. One case involved a complication of the ovum pick-up procedure; the woman had tubo-ovarian abscesses with infected hematomas. Because the abscesses were localized anteriorly in the lower abdomen and did not reach the pouch of Douglas, they could not be drained through a posterior colpotomy. Ultrasound guidance allowed us to drain all the areas of the multioculated abscesses. We suggest that percutaneous abscess drainage be the initial treatment of choice for tubo-ovarian abscesses before laparotomy is considered. PMID- 1495737 TI - Serous carcinoma of the peritoneum after oophorectomy. AB - BACKGROUND: Prophylactic oophorectomy in premenopausal women has been recommended to prevent ovarian cancer. However, serous carcinoma of the peritoneum, which is indistinguishable from ovarian carcinoma, can occur after oophorectomy. CASES: Two cases are reported of serous carcinoma of the peritoneum after oophorectomy. Presentation, management, and outcome are similar to those for ovarian carcinoma. CONCLUSION: More data are needed to quantify the risk of carcinoma after oophorectomy. Such knowledge may change the risk-benefit calculations of recommending prophylactic oophorectomy to premenopausal women at a certain age, and must be discussed with the patient who is considering prophylactic oophorectomy with or without other planned surgery. PMID- 1495738 TI - Giant ovarian leiomyoma associated with ascites and polymyositis. AB - BACKGROUND: Primary ovarian leiomyoma is rare. Most cases are asymptomatic; this benign neoplasm is usually found incidentally on routine pelvic examination, at surgery, or at autopsy. CASE: We present what we believe to be the first case of ovarian leiomyoma associated with ascites and polymyositis, both of which resolved after oophorectomy. This case emphasizes the important fact that preoperative evaluation may be inaccurate. CONCLUSION: Excision of a pelvic mass with histologic evaluation remains the only reliable way to establish a diagnosis. PMID- 1495739 TI - Meigs syndrome with elevated serum CA 125. AB - Elevation of serum CA 125 levels is associated with malignant serous ovarian carcinomas and has been described in one patient with Meigs syndrome. We present two additional cases of Meigs syndrome with significant elevations in serum CA 125 and report the results of immunohistochemical staining for CA 125. CA 125 expression was localized to the omentum and peritoneal surfaces rather than the fibroma. We suggest that expression of CA 125 and accumulation of ascites in these two patients may have resulted from some common peritoneal process. PMID- 1495740 TI - Intestinal invasion by a dysgerminoma in a patient with Swyer syndrome. AB - An unusual case is presented of advanced dysgerminoma in a patient with Swyer syndrome, 46,XY pure gonadal dysgenesis. Unexpected regional invasion necessitated bowel resection, total abdominal hysterectomy, and bilateral salpingogonadectomy for a complete en bloc excision of the primary tumor mass and the dysgenetic gonads. This report illustrates the possible need for extensive operative resection in patients with Swyer syndrome. PMID- 1495741 TI - Pseudomyxoma peritoneii: treatment with the argon beam coagulator. AB - The argon beam coagulator facilitates tumor debulking of peritoneal carcinomatosis. A patient with pseudomyxoma peritoneii originating from the left ovary with multiple peritoneal and omental implants was treated with the argon beam coagulator, enabling ablation of all gross disease. PMID- 1495742 TI - Accumulation of cis-diamminedichloroplatinum (II) and its analogues in sensitive and resistant human ovarian carcinoma cells. AB - Human ovarian carcinoma cell line (NOS2), established from a patient with serous cystadenocarcinoma of the ovary, has been exposed to a stepwise increase in cis diamminedichloroplatinum (II) (CDDP) concentration to produce a CDDP-resistant cell line NOS2CR) as an experimental model for resistance to CDDP. NOS2CR cells showed a 7-fold resistance to CDDP and a lesser degree of cross-resistance to diammine (1,1-cyclobutanedicarboxylato)-platinum (II) (CBDCA) and (-)-(R)-2 aminomethylpyrrolidine (1,1-cyclobutanedicarboxylato) platinum (II) (DWA2114R). In the absence of CDDP, cross-resistance to DWA2114R was reduced to the original level by 2 months, although 83% resistance to CDDP remained up to 6 months. To investigate CDDP-resistant mechanisms, alterations in the intracellular accumulation of CDDP and analogues were assayed by atomic absorption. In both NOS2 and NOS2CR cells, accumulation of CDDP increased linearly with time and was concentration-dependent. NOS2CR cells demonstrated 71, 52 and 12% reduction in accumulation of CDDP, CBDCA, and DWA2114R, respectively. These reductions did not seem to be due to P-glycoprotein, because expression of multidrug-resistant 1 gene was not detected in either NOS2 or NOS2CR cells. These studies indicate that the mechanisms of resistance to CDDP and analogues in NOS2CR cells are related in the main to reduced intracellular accumulation of drugs. DWA2114R might be helpful to treat CDDP-resistant and recurrent tumors which were treated by CDDP. PMID- 1495743 TI - Pain killing with calcitonin nasal spray in patients with malignant tumors. AB - The physiological role of calcitonin is the preservation of osseal integrity by reducing the osteoclast activity. On the other hand, this 32 amino acid peptide acts as an analgetic drug in cancer caused by osteolytic metastases. In previous studies using injection form the pain killing activity was observed in 65% of the patients. As medical assistance is required for this treatment form, it was decided to compare the pain reducing activity of nasal spray with the ampule form. It was found that 300 MRC units of nasal spray equalled 100 MRC units injection. The pain killing activity was observed in 53.8% of the patients. The reduction in quantity of other analgetics used daily was 48.5%. The average decrease of the pain duration (in h) was 42.5%. The pain intensity measured by visual analogue scale dropped to 2.13 from 3.00. The results are similar to the analgetic effect observed in the injection form. Taking this into consideration, calcitonin nasal spray is highly recommended instead of ampules. PMID- 1495744 TI - Mitomycin C and 5-fluorouracil salvage chemotherapy in platinum-resistant ovarian carcinoma. AB - Twenty-four patients with progressing or recurrent ovarian carcinoma, all pretreated with cisplatin, were evaluated for response and toxicity to mitomycin C (MMC) and 5-fluorouracil (5-FU) chemotherapy. Eligible patients had histologically proven intra-abdominal disease (67% clinically measurable; 33% nonmeasurable), and 67% of them had progressed on prior platinum-based chemotherapy. WHO response criteria were adopted in patients with measurable disease while those with nonmeasurable lesions were considered as responding in case of nonevident disease and CA-125 values less than 35 U/dl for at least 6 months. All patients received at least 2 treatment courses (median 6, range 2 10), and 5 patients (21%) could be considered as responding: 4/8 (50%) with nonmeasurable and 1/16 (6%) with measurable disease. The overall median survival was 12 months, range 7-30+ (median follow-up: 29.5 months, range 28-30). Progression-free survival was significantly different in responders (15 months) versus nonresponders (3 months) (p = 0.0001). Toxicity was mainly represented by myelosuppression (grade I 29%; II 8% and III 4%). MMC and 5-FU did not show significant activity against large tumor burden, while a relatively good activity was detected in patients with minimal disease. The limited toxicity and possible schedule modifications have to be taken into account for further investigation on selected patients. PMID- 1495745 TI - Development and validation of prognostic models in metastatic breast cancer: a GOCS study. AB - The significance of several prognostic factors and the magnitude of their influence on response rate and survival were assessed by means of uni- and multivariate analyses in 362 patients with stage IV (UICC) breast carcinoma receiving combination chemotherapy as first systemic treatment over an 8-year period. Univariate analyses identified performance status and prior adjuvant radiotherapy as predictors of objective regression (OR), whereas the performance status, prior chemotherapy and radiotherapy (adjuvants), white blood cells count, SGOT and SGPT levels, and metastatic pattern were significantly correlated to survival. In multivariate analyses favorable characteristics associated to OR were prior adjuvant radiotherapy, no prior chemotherapy and postmenopausal status. Regarding survival, the performance status and visceral involvement were selected by the Cox model. The predictive accuracy of the logistic and the proportional hazards models was retrospectively tested in the training sample, and prospectively in a new population of 126 patients also receiving combined chemotherapy as first treatment for metastatic breast cancer. A certain overfitting to data in the training sample was observed with the regression model for response. However, the discriminative ability of the Cox model for survival was clearly confirmed. PMID- 1495746 TI - Immunohistochemical detection of estrogen receptors on paraffin sections of normal, hyperplatic and carcinomatous endometrium. AB - The present study is the first dealing with the demonstration of estrogen receptors (ER) in up to 8-year-old paraffin blocks of endometrial curettage samples routinely fixed in 10% formalin. The Mab ER-ICA was used in a modified peroxidase-antiperoxidase method after pretreatment of paraffin sections with pronase. Eleven cases with proliferative, 11 cases with secretory endometrium, 20 cases with adenocystic, 21 with adenomatous hyperplasia and 27 endometrial adenocarcinomas were tested. The two main parameters, namely the percentage of ER positive cells and the intensity of the immunostaining, were higher in the proliferative phase followed in a declining sequence by adenocystic hyperplasia, adenomatous hyperplasia, adenocarcinomas and the secretory phase of endometrium. Interestingly, the intensity of the immunostaining showed a positive relationship to the percentage of ER-positive cells (r = 0.93, p less than 0.001). It seems that the immunohistochemical demonstration of ER in paraffin sections of uterine specimens is an easy and reliable method for the mapping of the heterogeneous expression of ER and their comparative study with the well preserved histopathological features even in old archival paraffin-embedded material. PMID- 1495747 TI - Pattern of growth factor, proto-oncogene and carcinoembryonic antigen gene expression in human colorectal carcinoma cell lines. AB - The aim of the present study was to examine whether the expression of growth factor genes, proto-oncogenes and carcinoembryonic antigen (CEA) gene in human colorectal cancer cell lines was related to their clinicobiological behavior. A significant variability among cell lines was detected for both insulin-like growth factor II and transforming growth factor beta gene message. Detectable levels of c-myc, Her-2, c-myb, K-ras and EGF receptor mRNA were found in most cell lines, whereas only 1/11 and 2/11 cell lines were positive for N-myc and c sis message, respectively. N-myc expression was limited to a cell line originated from a tumor with neuroendocrine features, while high levels of K-ras message were found only in a cell line derived from a radioresistant tumor. CEA mRNA levels correlated well with the concentration of antigen in each cell line. On the basis of these results, our findings demonstrated that human colorectal cancer cell lines show heterogeneous expression of growth factor and CEA genes and proto-oncogenes; however, with the exception of K-ras, N-myc and CEA, other correlations between gene expression and the clinicobiological characteristics of these cell lines could not be demonstrated. PMID- 1495748 TI - Effects of a preoperative therapy with interleukin-2 on surgery-induced lymphocytopenia in cancer patients. AB - It is known that major surgery may determine immunosuppression. This side effect might have a prognostic significance particularly in cancer patients, in whom the decrease in host defenses during the postoperative period could promote the proliferation of possible micrometastases. Since antitumor immune response is an IL-2-dependent phenomenon, a study was started to evaluate the effects of a preoperative injection of IL-2 on surgery-induced immune changes in cancer patients. The study included 12 colon cancer patients, treated subcutaneously with IL-2 at a dose of 9 x 10(6) IU/m2 twice daily for 3 consecutive days before surgery. Patients underwent surgery within 36 h from IL-2 interruption. The results were compared to those found in a control group of 18 colon cancer patients. Mean number of lymphocytes, T lymphocytes and NK cells significantly decreased after surgery in control patients; on the contrary, no postoperative decrease in immune cells was seen in IL-2 group. No anesthesiologic or surgical complication was seen in patients pretreated with IL-2 before surgery. This preliminary study would suggest that a preoperative therapy with IL-2 is an effective and well tolerated medical approach to neutralize surgery-induced immunosuppression in cancer patients. PMID- 1495749 TI - Intratumoral heterogeneity in DNA ploidy of bladder carcinomas. AB - In order to investigate whether DNA ploidy in a single area of a tumor could be representative of the entire tumor, flow-cytometric DNA analysis was performed for multiple samples (an average of 7 samples) obtained from the same tumor in 9 cases of transitional cell carcinoma of the urinary bladder. The incidence of DNA aneuploidy was 88.9% (8 out of 9 cases) and, furthermore, in 7 of these, intratumoral regional heterogeneity in DNA ploidy was evident. With high frequency, bladder carcinoma consisted of heterogeneous cell populations with different ploidy. There were 2 cases in which the tumor consisted of mixed subpopulations of diploid and aneuploid clones which were located in different parts of the same tumor. In such cases, an aneuploid line could not have been detected in a single specimen from the tumors. PMID- 1495750 TI - Studies of actinomycin D induced B23-translocation in P388D1 cells implanted in DBA/2 mice. AB - Nucleophosmin/B23 is a nucleolar phosphoprotein which redistributes from nucleoli to nucleoplasm (B23-translocation) when cells are exposed to certain anticancer drugs, particularly intercalators. The B23-translocation assay has been demonstrated in cell culture to correlate with drug effects and to detect drug resistant cells. We now report the effect of actinomycin D on B23-translocation in P388D1 cells implanted in DBA/2 mice. B23-translocation was observed in cells after actinomycin D treatment in a dosage- and time-dependent manner. Translocation could be observed within 30 min after drug treatment. Complete B23 translocation with at least 1-day duration was achieved by a single injection of 0.25 mg/kg. Reduced dosages produced partial B23-translocation with shorter durations. These results indicate that B23-translocation may be useful in monitoring drug effects in animals. PMID- 1495751 TI - Cytotoxicity of mitomycin C and carboquone combined with hyperthermia against hypoxic tumor cells in vitro. AB - Enhancement of the cytotoxicity of mitomycin C (MMC) and carboquone (CQ) by hypoxia at elevated temperature was examined using the SDI test of mouse Sarcoma 180 and Ehrlich cells and clonogenic assay of HeLa cells. When Sarcoma 180 and Ehrlich cells were incubated at 43 degrees C for 2-10 h, the hyperthermic effect was enhanced by hypoxia. The succinate dehydrogenase activity of the cells was reduced by hyperthermia to a greater extent in the presence of hypoxia (O2:5%) than under conditions of aeration (O2:20%). When the cells were exposed to various concentrations of MMC and CQ, under hypoxia, activity of the drugs was enhanced compared to the findings under conditions of aeration. The enhancement was prominent in case of drugs and hyperthermia combined. Clonogenicity of hypoxic HeLa cells was also reduced to a greater extent with this combination than in case of aerated cells. We tentatively speculate that hyperthermo chemotherapy using MMC and CQ has a potential to attack selectively hypoxic cells present in a solid tumor. PMID- 1495752 TI - Etoposide microcrystals suspended in oil: a new dosage form to peritoneal carcinomatosis in mice. AB - Etoposide microcrystals suspended in oil (ETOP-OIL) were examined for their therapeutic effects on peritoneal carcinomatosis in mice. Two days after intraperitoneal inoculation with 10(5) P388 leukemia cells/mouse to CDF1 male mice, etoposide at 10-80 mg/kg was administered intraperitoneally in bolus in the form of ETOP-OIL or in the aqueous solution form. In every dose, the survival curve of the mice given ETOP-OIL was statistically significantly improved in spite of its small lethal toxicity, as compared with those given the identical dose of etoposide aqueous solution. PMID- 1495753 TI - Chemopreventive action of selenium on methylcholanthrene-induced carcinogenesis in the uterine cervix of mouse. AB - The placement of cotton thread impregnated with beeswax containing methylcholanthrene (MCA, approximately 600 micrograms) inside the canal of the uterine cervix of virgin, adult mice results in the emergence of precancerous and cancerous lesions in the cervical epithelium. Employing this experimental carcinogenesis model system, the present study evaluates the chemopreventive action of selenium on the incidences of precancerous and cancerous lesions in the cervical epithelium. When selenium was administered through drinking water at the dose level of 1 ppm for 1 week before and 12 weeks following carcinogen thread insertion, the cervical carcinoma incidence, as compared to that in control mice (72%), was 37%. This decline in the incidence of carcinoma was significant (p less than 0.05). The incidences of hyperplasia and dysplasia show a decreasing trend with selenium treatment in MCA-thread-inserted animals. PMID- 1495754 TI - Effects of switching from a high-fat diet to a low-fat diet on tumor proliferation and cell kinetics of 7,12-dimethylbenz(a)anthracene-induced mammary carcinoma in rats. AB - We investigated the stimulatory effect of a high-fat diet on tumorigenesis, tumor proliferation and cell kinetics of 7,12-dimethylbenz(a)anthracene-induced mammary carcinomas in Sprague-Dawley rats, and sought to determine whether switching the animals from a high-fat diet to a low-fat diet would suppress tumor proliferation and cell kinetics. The high-fat diet significantly stimulated tumorigenesis, tumor proliferation and cell kinetics. After the animals were switched from the high-fat diet to the low-fat diet, however, tumor growth decreased, the BrdUrd labeling indices of tumors significantly decreased, and the potential doubling times of tumors significantly increased. Therefore, switching from a high-fat diet to a low-fat diet may improve the prognosis of breast cancer. PMID- 1495755 TI - Induction of neoplasms in Egyptian toads Bufo regularis by oil of chenopodium. AB - Feeding the Egyptian toad Bufo regularis with oil of the chenopodium plant induced hepatocellular carcinomas in 23% of the animals, and metastases of the primary liver tumors appeared in the kidneys of 6 toads. The earliest evidence of tumors appeared after 3 months of treatment. The average latent period of tumor induction was 3.6 +/- 0.4 months. It is speculated that oil of chenopodium may be one of the constituents of Chenopodium ambrosoides which is responsible for tumor induction in the toads B. regularis. PMID- 1495756 TI - [The detection and characteristics of substances with fibroblast growth factor properties in the cells of loach embryos]. AB - The substances extracted and partially purified from embryos of the loach (Misgurnus fossilis L.) at the late blastula stage are shown to possess properties characteristic of the fibroblast growth factor (FGF): 1) they bind with Heparin-Sepharose; 2) induce DNA synthesis in mouse NIH-3T3 and Swiss-3T3 fibroblast cell lines and in the primary culture of human embryonic fibroblasts; 3) have an apparent molecular weight of 15-16 kDa (according to SDS electrophoresis); and 4) show positive reaction with antibodies against bovine basic FGF. PMID- 1495757 TI - [The structural changes in chromatin at different levels of its organization during aging]. AB - The data about changes in the molecular organization of the cell nucleus during aging are reviewed. Changes in DNA primary and secondary structure include deletions of some sequences, changes in base methylation pattern and the increasing number of DNA breaks. Conditions underlying poor reproducibility of the results obtained in corresponding experiments are discussed. Changes observed in the nucleosomal and supranucleosomal chromatin structure reflect either its increasing compactization or the loss the nucleosomal structure during aging. The data about the increased DNA superhelicity and topoisomerase activity in aging organisms contradict the accepted views about age-related decrease in chromatin activity. It is suggested that the gene activity in aging organisms is specifically altered rather than generally decreased. The data are presented about the ways of preventing or reverting the age-related changes in chromatin structure. PMID- 1495758 TI - [The development of the thoracic duct lymphangions in the prenatal period of human ontogeny]. AB - This paper concerns structural and functional organization of the human lymphatic system during the prenatal period. For the first time the data is presented on the development of thoracic duct based on the concept of lymphangion as a structural and functional unit of a lymphatic vessel. The formation of the duct is considered in connection with structural changes of its wall and variants of duct roots fusion. The following stages are distinguished in the development of the thoracic duct: valval segment stage, protolymphangion, and lymphangion. PMID- 1495759 TI - [The effect of carbohydrate metabolic changes during pregnancy on the capacity of liver mitochondria in rat progeny to oxidize the lipid intermediate]. AB - Respiration rate, respiration control and ADP of liver mitochondria were studies in one-, ten-, and twenty-day-old rats born of females who had received subcutaneous insulin injections (0.25 U/100 g body weight) on days 5-7, 11-13 and 19-21 of pregnancy or glucose (1 g/100 g body weight, in the morning before feeding). Caprylate, an intermediate of the lipid metabolism, was used as the substrate for oxidation. In the control, caprylate oxidation in one-day old rats occurred at a low rate without providing for synthesis of ATP from ADP and phosphate. Insulin administration and alimentary hyperglycemia in females on days 5-7 of pregnancy had no significant effect on respiration rate of liver mitochondria in progeny of all ages tested. Administration of the above preparations on days 11-13 and 19-21 of pregnancy improved caprylate oxidation in mitochondria of the newborn rats. In other series the difference between experiments and the control was insignificant. Metabolic changes in the newborns are shown to be related to hyperinsulinemia in pregnant females. PMID- 1495760 TI - Preferential looking--clinical lessons. AB - Preferential looking-based tests of acuity have been available for over a decade. The authors discuss their use in clinical practice, particularly in three groups in whom acuity could not be quantified by traditional means: normal infants, and young children who are either mentally retarded, or who have visual disorders. Preferential looking (PL) testing has increased our understanding of the natural history of visual pathway disorders and has revealed certain patterns of acuity development. Early acuity development may be normal, delayed, or stationary, while in later infancy and childhood the following abnormal patterns have been identified: asymptotic, parallel, catch-up, or regressing. While this information has introduced a degree of complexity hitherto unknown which, if misunderstood, can lead to test misinterpretation, it offers the clinician invaluable information to improve patient care, and may also offer clues to the fundamental mechanisms of visual development. PMID- 1495761 TI - Update of sporadic microphthalmos and coloboma. Non-inherited anomalies. AB - The majority of patients with microphthalmos and colobomas have genetic disorders. This is a survey of non-inherited, sporadic microphthalmos. Such cases may occur in the Goldenhar, CHARGE and VATER associations; it may also be due to teratological agents, for instance maternal ingestion of drugs, maternal infection, fever or irradiation. In these cases it is possible that neural crest cell development is abnormal. Some drugs, for instance retinoic acid are regulators of Hox genes which control an ordered sequence of differentiation; coloboma or microphthalmos may appear if deregulation occurs. Large choristomas of the anterior segment of the eye may be associated with microphthalmos or anophthalmos. Encephaloceles or orbital tumours may deform the growing eye and are another cause of non-inherited microphthalmos. PMID- 1495762 TI - Autosomal dominant congenital miosis with megalocornea. AB - A family with AD congenital miosis is presented. The ocular symptoms were: megalocornea, iris translucency, microcoria with poor pupillary dilatation and goniodysgenesis with anterior insertion of the iris. This observation confirms that in congenital miosis abnormal development of the whole anterior eye segment may occur. The patients have an increased risk to develop glaucoma. If retinoscopy is impossible due to pin-point pupils, ultrasonic biometry to determine the axial length is recommended. An optical iridectomy could improve visual performance at low illumination; the complaints of photophobia, which are related to the iris translucency, persist. PMID- 1495763 TI - Peters' anomaly and combination with other malformations (series of 16 patients). AB - A series of 15 patients with Peters' anomaly observed from 1987-1991 and a patient showing Wolf-Hirschhorn syndrome were studied retrospectively. Combined ocular anomalies were: microphthalmos (9x), myopia (4x), aniridia (2x), cataract (2x). Five of the patients had combined general anomalies: mental retardation, deafness, cardiac malformation (ASD II), and luxatio coxae. In two of them chromosomal anomalies were found: 4p minus syndrome, mosaic trisomy 9. After comparison of these data with those known from the literature the author confirms that Peters' anomaly is a morphologic finding rather than a distinct entity. Treatment depends on individual histopathologic findings and on the psychophysical development of the child. PMID- 1495765 TI - Special issue in honour of Barrie Jay. PMID- 1495764 TI - Peters' anomaly. The spectrum of associated ocular and systemic malformations. AB - The cases of Peters' anomaly seen over the past decade, at Hospital Ste-Justine in Montreal, are reviewed. Associated ocular anomalies were observed in 50% of cases while 60% of patients presented with associated systemic defects. It is clear, from these patients and those reported in the literature, that Peters' anomaly can be an isolated condition, or part of distinct syndromes: the Krause Kivlin syndrome or the Peters'-plus syndrome. The authors emphasize the importance for the ophthalmologist to recognize these possibilities if proper management is to be provided. PMID- 1495766 TI - Mapping the eye diseases. AB - In this review the authors first give an overview of the general strategies of mapping which differ whether the biochemical (molecular) defect of the disease is known or not. The main problems besides mapping are concerned for the first category with the correlation between mutation and phenotype and for the second, with heterogeneity, genetic vs phenotypic. Finally, tables are displayed of eye diseases or diseases with eye involvement (metabolic or not) which have been currently mapped, as well as candidate genes actually or putatively involved in visual transduction. PMID- 1495767 TI - Horner's law. The first step in the history of the understanding of X-linked disorders. AB - Earlier reports on colour blindness are descriptions which almost always mention the familial occurrence. Horner's publications (1876), however, gave the first scientific analysis of the hereditary transmission of Daltonism. Since this genealogic study was published only in a local bulletin of the City of Zurich it seemed necessary to give a translation of the most important part of the article. 'Horner's law' says that colour-blind fathers have colour-normal daughters; and these colour-normal daughters are the mothers of colour-blind sons. In his first pedigree Horner demonstrates that colour-blindness is transmitted from the grandfather to the grandson. A second pedigree, however, shows the possibility that the transmission is also possible via female carriers through more than one generation. The similarity with the inheritance of haemophilia, published by Lossen (Heidelberg), was mentioned by Horner. In the further progress of genetic research the chromosomes were visualized, at first in tumour-cells 1881, in cells of human tissue. The final point in this development was the description of sex chromosomes, which made the interpretation of Horner's law possible by Wilson (1911), i.e., the localization of the pathologic gene of Daltonism on the X chromosome. PMID- 1495768 TI - Investigation of disease mechanisms in retinitis pigmentosa. PMID- 1495769 TI - Retinal angioma and juvenile sex-linked retinoschisis. AB - A 13-year-old boy presented with juvenile X-linked retinoschisis and in the right fundus a typical retinal angioma situated at the temporal site of the macula. A maternal uncle and a maternal grand uncle were known to be also affected by juvenile retinoschisis. Family history was negative for retinal angiomatosis. Extensive internal, neurologic and radiologic examinations did not reveal associated neurologic or visceral involvement in the affected child. The association of a retinal angioma and juvenile X-linked retinoschisis is most probably fortuitous. PMID- 1495770 TI - A practical approach to albino diagnosis. VEP misrouting across the age span. AB - In addition to the genetic heterogeneity in albinism, widespread clinical heterogeneity frequently impedes albino detection and differential diagnosis. Further, several auxiliary ocular and/or cutaneous manifestations of this inherited error of pigmentary metabolism are neither pre-requisite nor specific to the albino condition. However, one feature that is specific to albinism regardless of genotype or phenotype is a unique pattern of abnormal visual pathway organization. With an appropriate test paradigm, the albino visual pathway can be revealed by the non-invasive recording of the visual evoked potential (VEP) distribution across the occiput which shows contralateral hemispheric asymmetry following full field monocular stimulation. As described in this report, the VEP albino misrouting detection test has been refined to yield extraordinarily high sensitivity and selectivity across the age span from the neonate to the elderly. As the VEP profile undergoes maturational changes, these changes have been taken into account in the development of an albino age-range VEP test recipe which includes the pattern onset paradigm for older albinos and a luminance flash paradigm for the albino infant. The age appropriate optic pathway misrouting test provides reliable albino detection and definitive differential diagnosis. Further, as the albino VEP signature of contralateral asymmetry is also age specific, the VEP misrouting test can be extended to the objective assessment of visual pathway maturation. PMID- 1495771 TI - Aspects of albinism. AB - Genetic, clinical and electrophysiological aspects of albinism are described. Emphasis is placed on electrophysiological features which help to distinguish albinism from other clinical conditions, and on stimulating and recording factors which can affect the clarity of VEP results. PMID- 1495772 TI - Risk factors for postoperative endophthalmitis. PMID- 1495773 TI - Risk factors for postoperative endophthalmitis. PMID- 1495774 TI - Risk factors for postoperative endophthalmitis. PMID- 1495775 TI - Risk factors for postoperative endophthalmitis. PMID- 1495776 TI - Federal health care hoops and confused providers. PMID- 1495777 TI - Vision in the "good" eye of children treated for unilateral congenital cataract. AB - PURPOSE: The authors examined linear acuity and contrast sensitivity in the "good" (fellow) eye of children treated for unilateral congenital cataract to determine (1) whether there were subtle deficits like those described for the good eye of patients with strabismic amblyopia and (2) whether any deficits were related to the degree to which the good eye had been patched. METHODS: The authors tested patients treated for unilateral congenital cataract who had a well documented history of patching. The good eye was physically normal with minimal refractive error. The measures were linear acuity at far (n = 15) and contrast sensitivity (n = 9). RESULTS: Compared with age-matched control subjects, the good eyes of patients had subtle deficits in linear acuity and in contrast sensitivity at high spatial frequencies. These deficits occurred even in eyes that had received minimal patching, and their severity was not related systematically to the duration of patching, which varied widely across the group. CONCLUSION: The visual sensitivity of the good eye of children treated for unilateral congenital cataract is, on average, slightly reduced, even in cases of minimal patching. Consequently, any deficits discovered after aggressive patching may not have been caused by occlusion amblyopia. PMID- 1495778 TI - Surgical treatment of subluxated lenses in children. AB - BACKGROUND: Surgical removal of subluxated lenses had traditionally been discouraged because of concerns about poor surgical results and unacceptably high complication rates. METHODS: The authors reviewed the surgical results of 29 eyes in 15 consecutive patients who were operated on for subluxated lenses. RESULTS: Best-corrected visual acuity improved in all 29 eyes and was limited only by amblyopia. There were no significant complications in follow-up ranging from 5 months to 12 years. CONCLUSION: Modern surgical techniques using vitrectomy instruments allow the vitreous to be handled more effectively and have led to improved results and lower complication rates. Surgery for subluxated lenses can be done effectively and safely when indicated. PMID- 1495779 TI - Head nodding is compensatory in spasmus nutans. AB - BACKGROUND: Spasmus nutans is defined as asymmetric nystagmus with associated head nodding in childhood. It is not clear whether head nodding is a compensatory mechanism to control the nystagmus or an involuntary movement of pathologic origin. METHODS: The authors analyzed the relation between head and eye movements by simultaneous eye and head movement recordings of 35 patients with spasmus nutans. RESULTS: In 21 of these patients, the fine, fast, dissociated nystagmus changed during head nodding to larger and slower symmetric eye movements with both eyes oscillating at the same amplitude in phase and 180 degrees out of phase to the head movements, corresponding to a normal compensatory vestibulo-ocular reflex. CONCLUSION: These findings indicate that head nodding is compensatory in spasmus nutans. PMID- 1495780 TI - Tendon laxity in superior oblique palsy. AB - BACKGROUND: Some congenital superior oblique palsies are known to be due to anomalous or lax superior oblique tendons. This prospective study of 24 patients with a diagnosis of superior oblique palsy was performed to determine the prevalence and significance of anatomic tendon anomaly or laxity as diagnosed by traction testing of the superior oblique tendon. METHODS: Traction testing was performed on 24 consecutive superior oblique palsy patients to determine the relative laxity of the tendons. RESULTS: All 14 patients who were believed to have congenital palsy by history and clinical examination were found to have lax tendons. No patient with acquired unilateral palsy showed similar tendon laxity. CONCLUSION: These findings have significant implications regarding the diagnosis and possible cause of congenital superior oblique palsy as well as implications for surgical management. PMID- 1495781 TI - Ophthalmologic assessment of young patients with Alport syndrome. AB - BACKGROUND: Alport syndrome is an X-linked disease affecting basement membrane collagen. It is characterized by nephritis associated with high-tone sensorineural hearing impairment and ophthalmic signs. Although ocular changes have been described in adults, few data exist regarding the incidence of abnormal ocular features in adolescence and childhood. METHODS: Fifteen male and five female patients with Alport syndrome underwent ophthalmologic, audiologic, and nephrologic assessments. All patients studied had hematuria and a positive family history of Alport syndrome. Thirteen patients had a renal biopsy that showed characteristic electron microscopic changes of the disease. Eleven patients had high-tone sensorineural impairment. Electrophysiologic investigations performed included electroretinography, visual-evoked potentials, and electro-oculography. RESULTS: Two patients had early signs of anterior lenticonus, three had flecks in the retina, and two patients also had posterior subcapsular cataracts. None of the patients had significant electrophysiologic abnormalities. CONCLUSION: These findings indicate that ocular changes are uncommon and subtle in young patients with Alport syndrome, and suggest that the signs increase in frequency and severity with age. PMID- 1495782 TI - Contrast and glare sensitivity. Association with the type and severity of the cataract. AB - PURPOSE: Contrast and glare sensitivity tests are now being used as adjuncts to visual acuity in the assessment of visual function. Limited data are available on the associations of the former tests with cataract type and severity. The aim of the study is to assess these associations using standardized techniques. METHODS: Contrast sensitivity tests (using the Pelli-Robson chart) and glare sensitivity tests (using the Vistech MCT 8000) were done on 128 patients with cataracts and no other ocular disease and on 29 control volunteers. The cataracts were graded using the Lens Opacities Classification System II (LOCS II). Data from the left eyes were analyzed using logistic regression models. RESULTS: Contrast sensitivity loss was associated with cataract severity for cortical (P less than 0.0001) and posterior subcapsular (P = 0.0001) cataracts and with decreased visual acuity (P = 0.0001). Night and day glare sensitivity were each associated only with increased severity of posterior subcapsular cataracts (P less than or equal to 0.003) and with decreased visual acuity (P less than 0.001). Additional analyses showed that contrast and glare sensitivity were similar in eyes with no cataracts and early cataracts. CONCLUSION: These results suggest that the Pelli Robson Chart and the Vistech MCT 8000 are good techniques for evaluating visual function in moderate to advanced cataracts. However, for early cataracts, other techniques need to be explored to assess visual function loss. PMID- 1495783 TI - Quantitative analysis of wound healing after cylindrical and spherical excimer laser ablations. AB - PURPOSE: Superficial corneal ablation using the 193 nm excimer laser for the correction of myopia and astigmatism produces histologic changes in the corneal profile that can be quantitatively analyzed. METHODS: Using the excimer laser, spherical and cylindrical corneal ablations were performed on rabbit eyes at depths of 2, 4, 6, and 8 diopters. After 12 weeks, the corneas were examined histologically using a dichlorotriazinyl aminofluorescein stain for collagen, and the results were quantified using a digital video image analysis system. RESULTS: Epithelial thickness and thickness of new collagen were positively correlated with the depth of ablation after spherical ablations. With astigmatic ablations, epithelial thickness and new collagen production were correlated with ablation depth in one axis only. CONCLUSION: These results suggest that during cylindrical corneal ablations with the excimer laser, radially asymmetrical stromal ablations produce quantitatively asymmetrical wound healing. PMID- 1495784 TI - Risk analysis in the development of pterygia. AB - PURPOSE: No detailed analysis of risk factors in the development of pterygia has been previously performed. In this report, the authors identify and quantify these risk factors. METHODS: In a case-control study, 278 patients treated in a Brisbane hospital for primary pterygium between 1973 and 1978 were compared with a similar number of people without pterygium who were matched for age, race, and sex, using information from a standard questionnaire completed during a personal interview. RESULTS: Risk of pterygium was increased among patients who, in their third decade of life, worked outdoors in an environment with high surface reflectance of ultraviolet light compared with those who worked indoors. The elevation of risk was raised several hundred-fold among those subjects who worked mainly on sand compared with those who worked indoors when results were adjusted for associated risk factors. When risk was measured among subjects who worked in an environment that was mainly concrete, risk was increased almost 20-fold. Those subjects who spent their first 5 years of life at latitudes less than 30 degrees had almost 40 times the risk of pterygium than those living at latitudes greater than 40 degrees; spending the majority of times outdoors in these earliest years was associated with a 20-fold increase in risk of developing pterygium. There was a strong protective element in the wearing of regular glasses, sunglasses, or a hat. CONCLUSIONS: There is a strong suggestion of a causal relationship between ultraviolet light exposure and the development of pterygia during the early years of life and the cumulative exposure over the next 2 to 3 decades in occupations in which there is a high component of reflected ultraviolet light. PMID- 1495785 TI - Oral acyclovir for herpes zoster ophthalmicus. AB - BACKGROUND: Reports on the natural history of herpes zoster ophthalmicus stress its high morbidity related to vicious scars on eyelids, ocular complications, and post-herpetic neuralgia. Early treatment with oral acyclovir is effective, but the optimal duration of treatment has not been defined. METHODS: The authors performed a bicentric, prospective, randomized, double-masked study of 86 patients with acute herpes zoster ophthalmicus, within 72 hours of skin eruption, who received oral acyclovir (800 mg 5 times daily), either for 7 days (plus 7 days oral placebo) or for 14 days. All patients concomitantly received ophthalmic 3% acyclovir ointment; follow-up was at least 6 months. RESULTS: Statistical analyses of subjective symptoms, skin lesions, and ocular complications showed no significant differences between the groups, suggesting that a 7-day course of treatment was sufficient. Drug tolerance was good. Pooled data from both groups corroborated earlier reports that prompt treatment with oral acyclovir reduces the severity of the skin eruption, the incidence and severity of late ocular manifestations, and the intensity of postherpetic neuralgia. At 6 months, late ocular inflammatory complications were seen in 29.1% of our 86 patients, versus 50% to 71% of untreated patients described by others. Only 13% of our patients experienced post-herpetic neuralgia, which in no case required the use of analgesics. CONCLUSION: The authors believe it is not useful to prolong treatment with 800 mg of oral acyclovir 5 times daily for more than 7 days in herpes zoster ophthalmicus. This study confirms the efficacy of oral acyclovir not only against skin lesions and ocular complications, but also against postherpetic neuralgia in herpes zoster ophthalmicus. PMID- 1495786 TI - Panstromal Schnyder's corneal dystrophy. Ultrastructural and histochemical studies. AB - BACKGROUND: A large cohort comprising four kindreds of patients with Schnyder's dystrophy has been identified in central Massachusetts. All patients were Swede Finn with ancestry from the southwest Finnish coast on the Bay of Bothnia. METHODS: Of 60 members of this cohort examined by one of the authors (JSW), 18 had evidence of Schnyder's dystrophy. One female with Schnyder's dystrophy from each of three kindreds underwent penetrating keratoplasty for decreased visual acuity. We examined 4 corneal buttons from these unrelated women, aged 47, 63, and 72 years. RESULTS: The fluorescent probe filipin revealed that the majority of the lipid deposits were rich in unesterified cholesterol. Electron microscopy demonstrated abnormal accumulation of lipid and dissolved cholesterol in the epithelium, Bowman's layer, and throughout the stroma. Examination of the kindreds reflected the variable expression of crystals, which were present only in two patients, the 47-year-old and 63-year-old women. CONCLUSION: Ultrastructural and histochemical studies showed the panstromal localization of lipid in Schnyder's corneal dystrophy in three patients with Schnyder's dystrophy who underwent penetrating keratoplasty. PMID- 1495787 TI - Ocular surface alteration after long-term treatment with an antiglaucomatous drug. AB - BACKGROUND: This study was undertaken to see whether long-term locally applied ocular medications produced any alterations in the ocular surface, and, in particular, whether it caused damage to the mucus layer of the tear film. METHODS: The authors studied the ocular surface of 40 control subjects (group 1), 21 patients (group 2) chronically treated with a commercial preparation of 0.5% timolol maleate, and 20 previously untreated glaucomatous patients (group 3) in need of treatment with the same drug. Parameters studied were Schirmer's test, lacrimal meniscus height, break-up time, fluorescein and rose Bengal stains, conjunctival impression cytology, mucus staining, and the ferning test. RESULTS: Patients in groups 2 and 3 showed a significant decrease (P less than 0.001) in the number of normal Schirmer's and break-up time tests. All had positive vital stains. Results showed a significant decrease (P less than 0.001) in goblet-cell density, mucus granules, and reticular sheets, and an increase (P less than 0.001) in pathologic crystallization patterns. CONCLUSION: These results demonstrate that chronic application of a commercial preparation of timolol maleate damaged the ocular surface, especially the mucus layer of the tear film. PMID- 1495788 TI - Contact transscleral Nd:YAG laser cyclophotocoagulation. Midterm results. AB - BACKGROUND: Early reports of both contact and noncontact transscleral Nd:YAG laser cyclophotocoagulation have been encouraging; however, recent evidence indicates a significant incidence of hypotony, visual loss, and phthisis with the noncontact technique with more than 6 months of follow-up. The authors sought to determine the intermediate term effects of contact transscleral Nd:YAG laser cyclophotocoagulation (CYC). METHODS: The authors followed 116 eyes of 114 patients for a minimum of 1 year after treatment of advanced glaucoma with CYC. RESULTS: The mean preoperative intraocular pressure (IOP) of 35.0 +/- 1.0 mmHg decreased to 18.6 +/- 1.1 mmHg (P less than 0.0001) during the average follow-up of 19.0 +/- 0.6 months (range, 12 to 36 months). Intraocular pressure control of 3 to 25 mmHg was achieved in 72%, 3 to 22 mmHg in 65%, and 3 to 19 mmHg in 56% of eyes. Retreatment was required in 31 of the 116 eyes (27%). Intraocular pressure decreased to less than 3 mmHg in 9 eyes and to 0 mmHg in 6 of these 9 eyes. Nineteen eyes, all with initial visual acuity of counting fingers or worse, progressed to no light perception; 17 of 36 eyes (47%) with visual acuity of 20/200 or better lost 2 or more Snellen lines. CONCLUSION: Midterm results of CYC continue to be encouraging but are tempered by a nearly 10% incidence of hypotony or phthisis and the progression of visual loss. PMID- 1495789 TI - Effects of jogging exercise on patients with the pigmentary dispersion syndrome and pigmentary glaucoma. AB - BACKGROUND: Exercise-induced anterior chamber pigment dispersion with intraocular pressure (IOP) elevation has been reported in patients with the pigmentary dispersion syndrome. Marked pigment dispersion with or without elevation of IOP could predispose these patients to visual field loss. The authors designed this study to evaluate the effects of jogging exercise on anterior chamber pigment and IOP in a group of patients with the pigmentary dispersion syndrome or pigmentary glaucoma. METHODS: Fourteen subjects with the pigmentary dispersion syndrome, 10 subjects with pigmentary glaucoma, and 10 control subjects underwent a 45-minute protocol of jogging exercise. Anterior chamber pigment was graded and IOP was measured before and up to 3 hours after completion of the exercise protocol. RESULTS: Eyes of experimental subjects were significantly more likely to develop exercise-induced pigment dispersion than were eyes of control subjects. In experimental subjects, eyes treated with pilocarpine at the time of the study were significantly less likely to develop exercise-induced pigment dispersion than eyes not treated with pilocarpine. In two experimental subjects, pre exercise treatment with pilocarpine appeared to inhibit exercise-induced pigment dispersion. CONCLUSIONS: The authors do not believe that all patients with the pigmentary dispersion syndrome or pigmentary glaucoma need to avoid exercise. However, for patients with these disorders who regularly engage in jogging or more strenuous or more jarring types of exercise, they suggest an evaluation before and after the type of exercise in question. If marked exercise-induced pigment dispersion occurs, pilocarpine therapy may be an alternative to avoidance of the exercise. PMID- 1495791 TI - Neuroretinal rim area measurements by configuration and by pallor in ocular hypertension and glaucoma. AB - PURPOSE: The purpose of this study is to examine the differences between measurements of neuroretinal rim area of the optic disc defined by configuration and by pallor. METHODS: One hundred seventy-one patients were studied (59 with glaucoma, 96 ocular hypertensive patients, and 16 controls). The magnification corrected neuroretinal rim area was measured from black-and-white stereoscopic paper prints. The central area of pallor was measured using computer-assisted image analysis techniques. The percentage of central area of pallor was converted into mm2, and an estimate of neuroretinal rim area defined by color was calculated. RESULTS: The correlation between the measurements of neuroretinal rim area by configuration and by pallor was statistically highly significant (r = 0.89, P less than 0.0001). No consistent differences between measurements were found in different diagnostic groups, or in different stages or types of glaucomatous optic disc abnormality. The correlation of changes of both measurements during a 9-year follow-up period also was statistically significant (r = 0.68, P less than 0.001). CONCLUSION: In clinical routine measurements of the neuroretinal rim area, using both configuration and pallor definition does not seem to add to the information. PMID- 1495790 TI - Changes in reversal of cupping in experimental glaucoma. Longitudinal study. AB - BACKGROUND: The authors prospectively and longitudinally studied changes in optic disc topography during spontaneous reduction of intraocular pressure (IOP) in five monkeys with experimental glaucoma, using a computerized image analyzing system (Topcon IMAGEnet). METHODS: Glaucomatous optic neuropathy was produced in one eye of each animal by repeated argon laser photocoagulation of the trabecular meshwork. The duration of follow-up was 12 months. After laser treatment, IOP fluctuated and tended to increase. Spontaneous reduction in IOP was frequently observed during follow-up. Changes in optic disc parameters (vertical and horizontal cup-to-disc ratios, rim area/disc area, cup volume/disc area) that accompanied a given magnitude of spontaneous reduction in IOP at the early stage of glaucoma (first 4 months of follow-up) were compared with those at the later stage of glaucoma (last 4 months of follow-up). RESULTS: All optic disc parameters improved significantly during IOP reduction at each stage of glaucoma. Although there was no significant difference between the two stages in the magnitude of IOP reduction, the extent of improvement in each disc parameter was significantly less in the later stage than in the early stage. In both stages, reversal of cupping occurred symmetrically in the vertical and horizontal dimensions. Expansion of the cup occurred symmetrically in the early stage, but this was predominantly vertical in the later stage. CONCLUSION: These results suggest that the extent of cupping reversal after IOP reduction may decrease with progressive glaucomatous damage in primate glaucoma. PMID- 1495792 TI - Epibulbar molluscum contagiosum in acquired immune deficiency syndrome. Case report and review of the literature. AB - BACKGROUND: While molluscum contagiosum of the eyelid skin is commonly complicated by conjunctivitis, primary involvement of the conjunctiva or cornea by molluscum lesions is exceedingly rare. The authors studied a 34-year-old man with acquired immune deficiency syndrome (AIDS) in whom multiple molluscum lesions of the lids and a single nodule of the limbus developed. METHODS: The nodular lesion was excised from the limbus and processed for histologic examination by light microscopy. Pertinent literature concerning epibulbar molluscum contagiosum was reviewed. RESULTS: Histopathology of the excised lesion showed molluscum bodies within the acanthotic, hyperkeratotic conjunctival epithelium with surrounding chronic, nongranulomatous inflammation. Only 10 previous cases of conjunctival or corneal primary lesions have been reported, half of which showed associated cutaneous involvement. Lesions tended to be single, noninflamed, dome-shaped, and umbilicated, often with a yellowish central core. Patients were otherwise well and ranged in age from 3 to 55 years. Simple excision was effective in eradicating the lesions. CONCLUSION: Primary epibulbar molluscum contagiosum is rare. Although cutaneous molluscum is common in AIDS, this report is the first to document conjunctival molluscum in a patient with AIDS. PMID- 1495793 TI - Treatment of ocular adnexal Kaposi's sarcoma in acquired immune deficiency syndrome. AB - PURPOSE: To determine the most effective, safe, and cost-efficient treatment for ocular adnexal Kaposi's sarcoma in the acquired immune deficiency syndrome. METHODS: Eighty-two patients with ocular adnexal Kaposi's sarcoma related to the acquired immune deficiency syndrome were examined, and 25 were selected to participate in a 3-year study that treated the ocular lesions based on stage of development and location. RESULTS: Of 14 patients with bulbar conjunctival Kaposi's sarcoma treated with surgical excision, 2 stage III lesions recurred during a follow-up that ranged from 8 to 31 months; no stage I or stage II lesion recurred. Of 7 patients with eyelid Kaposi's sarcoma treated with cryotherapy, 2 stage III lesions recurred during a follow-up that ranged from 9 to 24 months; no stage I or stage II lesion recurred. Four patients with stage III Kaposi's sarcoma of the bulbar conjunctiva were treated with fluorescein angiography-based surgical excision. None of these lesions recurred during a follow-up that ranged from 4 to 8 months. CONCLUSION: A treatment regimen for ocular adnexal Kaposi's sarcoma related to the acquired immune deficiency syndrome based on tumor stage and location, using cryotherapy and surgical excision with or without fluorescein angiography, is effective, safe, and cost-efficient. PMID- 1495794 TI - Repair of telecanthus by anterior fixation of cantilevered miniplates. AB - BACKGROUND: The accepted surgical method for telecanthus repair is transnasal wiring. This procedure requires a stable posterior lacrimal crest on the affected side and surgical manipulation of the wires as they exit the contralateral side. A method for repairing telecanthus that obviates these prerequisites is presented. Indications for use of this technique and comparison to transnasal wiring is discussed. METHODS: A Y-shaped titanium rigid orbital plating system ("miniplate") was used to surgically correct traumatic telecanthus in five patients, two in the acute setting and three in late reconstruction. The miniplate was cantilevered from the lateral aspect of the nose and directed posteriorly into the orbit. This provided a stable fixation point for the medial canthal tendon. RESULTS: Marked resolution of the telecanthus was noted in four patients. No post-operative complications have been encountered to date. CONCLUSIONS: Miniplate fixation was used successfully to repair unilateral traumatic telecanthus. Miniplate fixation of the medial canthal tendon should be considered in unilateral cases of traumatic telecanthus and in cases where poor bony support for transnasal wires is evident. PMID- 1495795 TI - Tricompartment model of the lacrimal pump mechanism. AB - BACKGROUND: The role of the lacrimal sac in the lacrimal pump mechanism is controversial. METHODS: Movements of the lateral wall of the lacrimal sac with blinking were videotaped through an endoscope in eight patients after dacryocystorhinostomy. In addition, movements of an air bubble at the opening of the nasolacrimal duct with blinking were studied in three patients with an incompetent valve of Hasner. RESULTS: The superior half of the lateral wall of the lacrimal sac moved laterally with lid closure and medially with lid opening. The inferior half of the lateral wall of the lacrimal sac moved medially with lid closure and laterally with lid opening. In patients with an incompetent valve of Hasner, the air bubble at the opening of the nasolacrimal duct bulged into the nose with lid closure and retracted into the nasolacrimal duct with lid opening. CONCLUSIONS: A tricompartment model of the lacrimal pump is presented that incorporates these findings. With lid closure, the orbicularis muscle contracts, compressing the canaliculi and pulling the superior half of the lateral wall of the lacrimal sac laterally. This creates a lower pressure in the superior sac, allowing tears to be propelled from the canaliculi into the sac. At the same time, the inferior half of the lateral sac wall moves medially, creating a positive pressure in the inferior sac and nasolacrimal duct, thus forcing tears down the duct into the nose. With lid opening, the orbicularis muscle relaxes, allowing the canaliculi to open and the superior half of the lateral sac wall to move medially. The resulting negative intracanalicular pressure allows tears to flow from the lacrimal lake into the canaliculi, and the higher pressure in the superior sac closes the valve of Rosenmueller and forces tears from the superior to inferior sac and proximal nasolacrimal duct. At the same time, the inferior half of the lateral sac wall moves laterally, resulting in a negative pressure in the inferior sac and nasolacrimal duct. PMID- 1495796 TI - Diagnosis of cavernous sinus arteriovenous fistula by measurement of ocular pulse amplitude. AB - BACKGROUND: The ocular pulse amplitude (OPA), the difference between the maximum and minimum intraocular pressure (IOP) during the cardiac cycle, has been reported to be elevated in the eye ipsilateral to a cavernous sinus arteriovenous fistula. METHODS: The OPA was measured with a pneumotonometer in three groups of patients. Patients in group 1 had no orbital disease (n = 50), patients in group 2 had either unilateral or asymmetric orbital disease (n = 30), and patients in group 3 had angiographically proven cavernous sinus arteriovenous fistulas (n = 15). RESULTS: Patients in group 3 had a higher OPA than patients in either group 1 (P less than 0.001) or group 2 (P less than 0.001). The difference in OPA between an individual's eyes (delta OPA) also was higher in patients with cavernous sinus arteriovenous fistulas than in patients without fistulas (P less than 0.0001). CONCLUSION: A delta OPA of more than 1.6 mmHg was 100% sensitive and 93% specific in identifying patients with cavernous sinus arteriovenous fistulas. There was no difference in delta OPA between direct and dural cavernous sinus arteriovenous fistulas. Successful transvascular embolization of the cavernous sinus arteriovenous fistula normalized the delta OPA by reducing the OPA on the affected side. PMID- 1495798 TI - Transforming growth factor-beta 2 for the treatment of full-thickness macular holes. A prospective randomized study. AB - BACKGROUND: Full-thickness macular holes generally cause a significant reduction in visual acuity, due in part to a rim of surrounding neurosensory retinal detachment and retinal thickening. Recent studies have suggested that flattening of this narrow rim of neurosensory detachment can result in improved visual acuity. However, the ability to flatten the neurosensory detachment is limited using current surgical techniques. METHODS: Transforming growth factor-beta 2 (TGF-beta 2) is a recently discovered potent stimulator of wound healing. The authors, therefore, performed a prospective randomized study of 60 patients to determine if the local application of TGF-beta 2 to the edge of the macular hole can reproducibly induce flattening of the surrounding neurosensory detachment. The results of a study designed to determine the effect of a pars plana vitrectomy, fluid-gas exchange, and intravitreal instillation of TGF-beta 2 in eyes with a full-thickness macular hole and reduced visual acuity are reported. RESULTS: After treatment, visual acuity improved 2 lines or more in 5 of 11 eyes treated with 70 ng, in 4 of 12 eyes treated with 330 ng, and in 10 of 11 eyes treated with 1330 ng of TGF-beta 2. In some eyes, hyaluronic acid was added. In these cases, visual acuity improved 2 lines or more in 0 of 9 eyes treated with 70 ng TGF-beta 2, in 2 of 8 eyes treated with 330 ng, and in 4 of 9 eyes treated with 1330 ng. CONCLUSION: Logistic regression analysis demonstrated a statistically significant beneficial effect of TGF-beta 2 on visual improvement (P = 0.003). PMID- 1495797 TI - Retinal manifestations of ocular lymphoma (reticulum cell sarcoma). AB - BACKGROUND: Diagnosis and treatment of ocular large cell lymphoma may lessen visual loss and prolong life. Although reports in the literature have described retinal infiltrates in eyes with large cell lymphoma, they have focused on the more prominent vitreous and subretinal pigment epithelial findings. Eyes with retinal infiltrates and hemorrhagic retinal necrosis are usually believed to harbor a microbial infection. The authors describe 5 patients, aged 57 to 85 years, with ocular lymphoma in whom the most prominent initial findings were in the retina. METHOD: Patients presented with findings suggestive of an infectious retinal necrosis. When the initial therapy failed, investigators performed a vitreous biopsy. Two patients had a concomitant retinal biopsy. Radiation therapy was given to four patients. RESULTS: All five patients had vitreous cells. Three patients had prominent perivascular exudate. Four patients had grayish-white retinal infiltrates, and three patients had associated retinal hemorrhage. Three patients had subretinal small white spots. An edematous thickened retina developed in three patients, and hemorrhagic retinal necrosis developed in three patients. The initial diagnosis was believed to be acute retinal necrosis (ARN) in three patients, toxoplasmosis in one patient, and frosted branch angiitis in one patient. Vitreous biopsy was positive in two patients but negative in three patients. In two of these three patients, the diagnosis was established by retinal biopsy. CONCLUSION: Ocular lymphoma should be considered in the differential diagnosis of retinal vasculitis or necrotizing retinitis in a middle aged or older patient. Retinal biopsy may be helpful in establishing the diagnosis. PMID- 1495799 TI - A survey of intraocular silicone oil use in the United States. AB - PURPOSE: This survey was conducted to determine the pattern of usage of intravitreal silicone oil in the United States. METHODS: A questionnaire was sent to 542 members of the Retina and Vitreous Societies in December 1990, and again 6 weeks later in an attempt to improve the response rate. RESULTS: Two hundred eighty-seven questionnaires (53%) were returned. Ninety-eight percent of the respondents perform vitreous surgery, and 61% of them use silicone oil. This survey determined the degree of participation in Food and Drug Administration (FDA)- and institutional review board-approved protocols and the most common indications for use of silicone oil. Ninety-six percent of the respondents indicated that the use of silicone oil represented an acceptable standard of care. CONCLUSION: Silicone oil is widely used in the United States despite its lack of FDA approval. PMID- 1495800 TI - The future of patient input into medical decision making. PMID- 1495801 TI - How to start a direct patient care team. AB - Many American hospitals are embracing the philosophies of continuous quality improvement (CQI) or total quality management (TQM). To date, case studies in the literature have largely dealt with administrative processes. However, CQI can also improve direct patient care (clinical) processes using direct patient care teams. The establishment of such teams has been an elusive task at many organizations, largely because of the traditional paradigm of the appropriate relationship between provider and patient. However, similarities between direct patient care teams and other cross-functional teams far exceed differences. Using case studies from two teams (HIV and chest pain) at HCA West Paces Ferry Hospital and Southeastern Health Services, this article suggests ways facilitators can help providers examine, redesign, and improve direct patient care processes. PMID- 1495802 TI - Advancing the epidemiology of injury and methods of quality control: ACEs as an outcomes-based system for quality improvement. AB - Accelerated-compensation events (ACEs) are classes of avoidable medical injuries. Originally, these classes were used in tort reform to speed payment for avoidable injuries. However, ACEs also have potential as tools to monitor and improve the quality of health care. ACEs are developed by physicians, based on medical decision making. Rather than simply identify an adverse outcome, they link that outcome to clinical processes. Therefore, ACEs can help identify the critical elements of care that would result in desirable outcomes. Also, ACEs are discerning: they identify only events of which the vast majority are preventable. In one project, ACEs have been developed for obstetrics/gynecology, general surgery, and orthopedic surgery, using a three-phase process of sifting data and honing definitions. Future plans include improving these ACEs, statistically evaluating them, and testing them for utility in quality monitoring and improvement. PMID- 1495803 TI - [Childhood accidents]. AB - A survey of accidents in a period of one year in County Vas, Hungary was performed. The injury of children in the age-group of 0-14 was found in case 5841 i.e. in 22.5% of the total number of the injured. The incidence was 101/1000 head of puerile population. The rate of accidents appeared to be low in early childhood while it showed a significant increase in the school age. The home accidents accounted for the most of the accidents especially in the early childhood. Over the age of 7 the school and sport/playground accidents exceeded. The roads were involved as a high risk factor for each of the age groups. The high (21.5%) rate of fractures indicates severity of the injuries although the number of the most severe injuries remained low. The accident conditions of County Vas are at an advantage compared with international data meanwhile the high rate of accidents in the school age group calls for prevention and educational work. PMID- 1495804 TI - [Experience with surgical treatment of osteosarcoma]. AB - The authors treated 79 patients with osteosarcoma by surgery and chemotherapy 1975 through 1991. The appearance, localization and differential diagnosis are discussed. Attention is called to the doctor's delay. The effective pre- and postoperative chemotherapy decreased the incidence of the lung metastases and increased the survival rate (71% 3 years overall survival and 41% 5 years survival) and made the limb-sparing surgery possible. The development of the reconstructive surgical technique and new designs of tumor endoprostheses enabled us to perform limb-sparing surgery in more than one third of the cases at the same survival chance. The limb-sparing means a decisive change in the quality of the rehabilitation of the osteosarcoma patients. PMID- 1495805 TI - [Why is the Doppler pressure gradient higher than the one measured by catheter?]. AB - Hemodynamic assessment of aorto-iliac occlusive disease is necessary for successful arterial reconstruction of the legs. Various methods have been proposed and the "pull-through" intra-arterial pressure measurement method is accepted as the best standard. The pressure readings, however, seemed to depend on the intraluminal position of the catheter. To explain these observations and make a comparison between the Doppler method and the "pull-through" method, we have studied center-line velocity changes at the stenosis throat by Doppler ultrasound, and axial and lateral pressure gradients using pressure transducers, mounted 10 mm and 40 mm downstream of short (4 mm) and long (40 mm) axisymmetric sharp-edged model stenoses having cross sectional reduced areas of 64%, 84%, 91%, and 96%. Axial manometric pressures measured 10 mm after the throat of 84% stenosis were more than twice as high as the lateral pressures. There was no significant difference between axial and lateral pressures measured 40 mm downstream from throat. This pressure distribution has important clinical relevance. Mean and peak pressure gradients for both the Doppler method and manometric measurements were compared. Measurements with Doppler method and manometric measurements, indicated that mean pressure gradients (r = 0.98; SEE = +/- -2.4 mmHg) correlate better than peak pressure gradients (r = 0.90; SEE = +/- 16.5 mmHg). Doppler gradients were higher than manometer gradients. Overestimation was 13% for mean pressure gradients, and ranging from 10% to 150% for peak pressure gradients. Explanation for the difference between mean Doppler and catheter gradient may be the pressure recovery occurring in the relaminarized poststenotic regions. PMID- 1495806 TI - [SPECT follow-up of cerebral blood circulation after stroke]. AB - rCBF SPECT investigations with 99mTc-HMPAO were performed in 22 completed ischemic stroke patients on average 2.5, 16.8 and 38.0 days after stroke onset. As control group, 12 neurologically healthy volunteers were examined with the same method. The overall sensitivity of the rCBF SPECT method in the detection of cerebral blood flow abnormalities was 91%, with a specificity of 83% and an accuracy of 88%. The rCBF study was highly effective, particularly in the acute phase of the disease. Regional increased tracer uptake or a false normal 99mTc HMPAO distribution due to the developing hyperemia mostly complicated the rCBF image interpretations in the subacute period. In the chronic phase, the spatial resolution of the SPECT system limited the detection of the continuously retracted stroke lesions. PMID- 1495808 TI - Annual meeting of the American Academy of Otolaryngology-Head and Neck Surgery Foundation, Inc. Washington, D.C., September 13-17, 1992. Official program and abstracts. PMID- 1495807 TI - [Rhabdomyolysis in a medical student induced by body-building exercise (rhabdomyolysis following acute muscular exertion)]. AB - A medical student sportsman had been admitted to the hospital because of weakness and painful swelling of the muscle as well as dark urine appearing after carrying out an excessive body-building performance. On the basis of indirect evidences pigmenturia "per exclusionem" was a manifestation of urinary myoglobin excretion. The development of an "acute exertional rhabdomyolysis" was confirmed by the increased serum enzyme levels and myoglobinuria. The outcome of the illness was fortunate, as acute renal failure could be avoided. On the basis of survey of the literature it can be stated, that this presumably frequently occurring, but rarely recognized disease may have importance from clinical, sporting medicine and pathophysiological point of view. PMID- 1495809 TI - Clinical pharmacology of migraine. PMID- 1495810 TI - [Migraine according to the International Headache Society]. AB - The classification of headache and facial pain established by the International Headache Society (IHS) in 1988 is a useful tool for general practitioners, specialists and scientists. This classification provides a detailed description of the diagnostic criteria for the different forms of migraine headache, ranging from common migraine with or without an aura to less frequent or atypical forms such as migraine without headache or periodic syndromes of childhood. PMID- 1495811 TI - Migraine--disease or syndrome? AB - Migraine is a common condition with, usually, stereotyped symptomatology, suggesting that it is a specific disease entity (a morbus sui generis). However, occasionally a migraine sufferer will exhibit atypical manifestations of the condition; also, some specific diseases such as systemic lupus erythematosus and arteriovenous malformations, may exactly mimic the symptoms of migraine. These latter considerations raise the possibility that migraine is a syndrome rather than a disease. The recent delineation of the trigeminovascular system allows a conception of migraine as being neither disease nor syndrome, but rather a constitutional predisposition of the neurovascular system to react excessively to internal or external stimuli by a pattern of hyperactivity of the brain and of the trigeminovascular apparatus. Activation of the trigeminovascular system, whether by neural impulses from the brain or humoral factors in the circulation, results in vascular headaches, while associated activity in the brain may produce such typically migrainous symptomatology as prodrome and aura, and nonspecific symptoms such as nausea, vomiting and dizziness. In this model specific diseases may gain access to the trigeminovascular apparatus, detonating it to produce vascular headaches and neurological symptomatology which may more or less exactly mimic migraine. PMID- 1495812 TI - Migraine and heredity. AB - Since the time of Liveing and Gowers in the nineteenth century, migraine has been thought to be inherited, although family history has been widely studied, nearly all the reports are not scientifically based and studies on twins have never shown 100% concordance in monozygotic (MZ) pairs, indicating that migraine cannot be inherited by a single gene. Furthermore, the criteria for a polygenic trait are not fulfilled by migraine patients. The only two syndromes with a strong genetic basis of inheritance are familial hemiplegic migraine and migraine occurring in Mitochondrial Encephalomyopathy with Lactic Acidosis and Stroke-like episodes (MELAS). It is the predisposition to headache that is likely to be inherited; this is supported by the induction of migraine-like headaches with either m-chlorophenyl-piperazine (m-CPP) or nitroglycerin in normal subjects with a positive family history for migraine. PMID- 1495813 TI - [Electrophysiologic investigations in migraine]. AB - This article is a critical review of standard electroencephalography (EEG), brain mapping, evoked potential, and electromyography (EMG) studies carried out in various forms of migraine during and between attacks. With the exception of contingent negative variation, the exteroceptive silent period of the temporalis muscle, and possibly fast activity in response to visual stimuli, which are useful for the differential diagnosis of functional headache, the main value of electrophysiologic studies is to provide insight into the pathophysiology of the disease. Results of the different methods consistently indicate that the brain of migraine patients is characterized by hypersensitivity to some forms of stimuli between attacks and by, often focal, hypoactivity during attacks. PMID- 1495814 TI - [Platelets and migraine]. AB - Platelet function studies in migraine patients have evidenced a number of anomalies (hyperreactivity and serotonin metabolism disorders) that have been suggested as causative factors in migraine attacks. However, a review of the literature shows that these disorders are inconsistent and are probably consequences rather than causes of the headache, although they may contribute to the pathophysiology of the attack. From a broader perspective, the demonstration of platelet dysfunction in migraine raises questions as to the source of these disorders (secondary to plasma factors or due to platelet anomalies) and their significance (do they have any link with transient ischemic attacks or central serotonin neurotransmission dysfunction?). PMID- 1495815 TI - Cerebral blood flow in migraine with aura. AB - Pathognomonic changes in regional cerebral blood flow (rCBF) have gradually been described during the last decade. They support spreading cortical depression as the mechanism underlying the migraine aura but are not the direct cause of pain since they are absent in migraine without aura and are present in migraine aura without pain. Dilatation of intra- and extracranial arteries, on the other hand, takes place in both forms of migraine and seem closely associated to the pain. Dilatation and perivascular nociceptor sensitization may, very likely, be caused by neuropeptides and monoamines released from perivascular nerves and/or mast cells. PMID- 1495816 TI - [Cerebral blood flow in migraine without aura]. AB - For several years, cerebral blood flow (CBF) studies have been fueling the controversy surrounding the pathophysiology of migraine headache. The earliest studies focused mainly on migraine with aura (MA+) and provided evidence in support of the classical hemodynamic theory: a decrease in blood flow during the aura is followed by reactive vasodilation during the headache phase. Studies in migraine without aura (MA-), although less numerous, consistently demonstrated an increase in CBF during the attack. Olesen et al., gave rise to a heated debate by suggesting that hemodynamic manifestations are different in MA+ and MA-; in their view, CBF remains unchanged in MA-, whereas MA+ is associated with a wave of posterior blood flow deficiency which slowly spreads forwards in a manner reminiscent of experimental spreading depression; they interpret this hemodynamic pattern as evidence that the attack is mainly caused by a neural mechanism rather than a vascular spasm. This concept of MA- with no hemodynamic changes suggests that the pathophysiology of MA- may be completely different from that of MA+. However, most studies using stationary detectors or single photon emission computerized tomography (SPECT) with Xenon 133 or HMPAO as the tracer have demonstrated increased CBF during migraine attacks. The increase was not correlated with the side of the pain suggesting that vasodilatation is not the only cause of the pain. Current data do not seem to support the view that MA- and MA+ are different pathophysiologic entities; whether the mechanism of the attack is neural or vascular cannot be determined on the basis of CBF data.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1495817 TI - Spreading depression and migraine. AB - Cortical spreading depression (CSD) is a slowly-moving suppression of electrical activity that travels across the cortex at a rate of 2-5 min-1. CSD is transient, and accompanied by a severe disruption of ion homeostasis, depolarization of nerve cells and enhanced energy metabolism. The slow march of migraine prodromes has many features in common with CSD. On this background it has been suggested that CSD is a mechanism of migraine. Recently, the notion has gained renewed credibility with the demonstration of unique abnormalities of brain blood flow, energy metabolism and magnetoencephalography during migraine attacks which have been replicated point-by-point in the animal model during CSD. Simultaneously, a series of experiments have indicated that CSD is closely linked to activity of the N-methyl-D-aspartate (NMDA)-subtype of the glutamate-receptor. It is suggested, that N-methyl-D-aspartate-antagonism could be the next bid of a rational migraine therapy. PMID- 1495818 TI - [Neuro-imaging studies in migraine]. AB - Neuroimaging studies in migraine patients are useful for three important reasons. 1) Brain imaging techniques and primarily CT-scan should be used in every patient with atypical or complicated migraine to rule out a vascular malformation or brain tumor; 2) angiography, which was extensively used in the 1960's and 1970's, discloses a number of arterial anomalies including spasm or occlusion, of unclear pathogenic significance; 3) T2-weighted magnetic resonance images in migraine often show increased signals generated by the white matter; this finding is as yet poorly understood but is undoubtedly related to factors very different from those seen in elderly patients or patients with vascular risk factors. PMID- 1495819 TI - [Positron emission tomography and migraine]. AB - Positron emission tomography (PET) is a brain imaging technique that allows in vivo studies of numerous physiological parameters. There have been few PET studies in migraine patients. Cerebral blood flow changes with no variations in brain oxygen consumption have been reported in patients with prolonged neurologic manifestations during migraine attacks. Parenteral administration of reserpine during migraine headache has been followed by a fall in the overall cerebral uptake of glucose. The small sample sizes and a number of methodologic problems complicate the interpretation of these results. Recent technical advances and the development of new PET tracers can be expected to provide further insight into the pathophysiology of migraine. Today cerebral cortex 5 HT2 serotonin receptors can be studied in migraine patients with PET. PMID- 1495820 TI - NMR spectroscopic and magnetoencephalographic studies in migraine with aura: support for the spreading depression hypothesis. AB - The authors propose that patients who suffer from migraine with aura have a susceptibility to spontaneous neuronal discharges and subsequent spreading depression. This is based upon a state of central neuronal excitability involving the excitatory neurotransmitter glutamate, in combination with supersensitivity of the N-methyl-D-aspartate (NMDA) receptor. This hypersusceptibility is supported by increased turnover of high-energy phosphates, low intracellular Mg2+ and large amplitude depolarizing waves on magnetoencephalography (MEG). PMID- 1495821 TI - [Methodology of clinical trials in migraine: a rating system]. AB - Several problems confront trials of drugs for migraine: no clinical or biological markers for objective diagnosis are available, severity of the attack cannot be readily evaluated, the placebo effect is significant, and both compliance with therapy and patient follow-up may be difficult to ensure. No statistical method is capable of solving these problems and it is the clinicians' role to minimize them by consistent efforts at establishing good communication with their patients during the trial. Because of these significant intrinsic difficulties, trials of drugs for migraine require especially stringent data collection and analysis protocols in order to minimize the risk of errors which exist in any drug trial. The protocol used have not always been satisfactory with this respect. A rating system for helping non-specialists to evaluate the reliability of migraine drug trials is proposed. PMID- 1495822 TI - Migraine triggers: practice and theory. AB - The basis of our belief in migraine triggering factors is questioned. To avoid creating migraine-mythology, it is proposed that a trigger for migraine must also cause headache in non-migrainous subjects. This headache-migraine parallelism is examined and if correct, casts doubt on migraine precipitation by cheese, chocolate or allergy. A further weakness of "dietary migraine" is pointed out because the quantity of the trigger consumed, or the time interval between ingestion and the onset of attacks, are rarely mentioned, let alone studied. A difficulty in assessing migraine precipitants is that two factors may act in unison, e.g. stress and not eating. Further an external factor may provoke an attack only if the migraine "milieu interiur" is set appropriately, for example the hormonal state in a woman's menstrual cycle. The value of studying migraine precipitants is two-fold: (1) it provides a means of counselling patients to avoid or reduce these factors, thereby diminishing frequency and severity of attacks; (2) a comprehensive migraine pathogenetic theory must incorporate how and where precipitants act. It is concluded that analysis of triggering mechanisms lends support to the concept that migraine is a primary neurological disturbance with secondary vascular manifestations. PMID- 1495823 TI - [Migraine and non-steroidal anti-inflammatory agents]. AB - Controlled studies of nonsteroidal antiinflammatory drugs (NSAIDs) for the management of migraine attacks or for the prophylactic long-term treatment of migraine are reviewed herein. A large number of NSAIDs have been tested against a placebo or reference drug, including aspirin, indomethacin, mefenamic acid, tolfenamic acid, flufenamic acid, ibuprofen, flurbiprofen, fenoprofen, naproxen and sodium naproxen, diclofenac and lornoxicam. For the treatment of acute attacks, published studies found that the NSAIDs were significantly more effective than the placebo and at least as effective as the reference drugs. Adverse effects were absent or mild in this indication. Studies of NSAIDs as prophylactic treatment of migraine attacks are less numerous but also point to the value of this approach. However, long-term use of NSAIDs is associated with side-effects, mainly involving the gastrointestinal tract. PMID- 1495824 TI - [Alteration of bacteria induced by subinhibitory concentrations of cefixime: consequences on bactericidal activity of human polynuclear neutrophils]. AB - Subinhibitory concentrations of most parenteral cephalosporins have been reported to alter bacterial infectivity and, in particular, to increase the susceptibility of altered bacteria to the killing effects of polymorphonuclear neutrophils (PMN). Few data on this issue are available for oral cephalosporins. This study investigated the effects of sub-MIC concentrations of the new oral cephalosporin cefixime on two bacterial targets, i.e., S. aureus 209P (MIC 20 mg/l) and E. coli K12 (MIC 0.15 mg/l). After overnight incubation (18 hours) with 10 or 5 mg/l cefixime, susceptibility of S. aureus to the killing effects of PMNs was increased two-fold as compared with control organisms and susceptibility to the O2-independent PMN bactericidal system (PMN extract) was also increased. In contrast, the susceptibility of E. coli to PMN and to cell-free bactericidal systems was identical for cefixime-exposed strains (0.1 and 0.05 mg/l) and for unexposed controls. However, cefixime-exposed E. coli were filamentous, suggesting that bactericidal efficacy in terms of the bacterial mass eliminated was enhanced in exposed strains. These data show that low levels of cefixime are capable of producing major alterations in susceptible and resistant bacteria and of increasing their susceptibility to PMN. These effects may be relevant in vivo, in particular when low concentrations of antibiotics persist over long periods in infected sites. PMID- 1495825 TI - [Pseudomonas aeruginosa and imipenem: correlation between membrane protein D2 and resistance in fifteen strains isolated from patients with mucoviscidosis]. AB - A characteristic feature of imipenem-resistant strains of Pseudomonas aeruginosa is loss or decreased expression of the outer membrane protein (OMP) D2, whose molecular weight is 45 to 49 kDa. D2 was studied in 15 strains of P. aeruginosa with intermediate susceptibility or resistance to imipenem recovered from the sputum of 15 patients with cystic fibrosis. The OMP was extracted using Sarkosyl and separated by SDS-PAGE electrophoresis. Electrophoresis patterns were compared to those of reference strains 3B and 3C which are resistant and susceptible to imipenem, respectively. Expression of D2 was normal in three strains, weak or very weak in 11 strains and absent in one strain. For 12 strains, the alteration of the D2 protein was consistent with previous reports. However, the finding of normal D2 production in three strains is unusual and suggests the possible presence of another mechanism of resistance. PMID- 1495826 TI - [Effect of the administration of cefixime on aerobic fecal flora in children]. AB - The ecological effect of cefixime on aerobic fecal flora was evaluated in 6 children aged 2 to 5 years given oral cefixime (8 mg/kg/day in two divided doses) for five days. Serial dilutions of stools recovered at baseline (D0), 2 and 5 days after initiation of therapy (D2 and D5) and two days after completion of therapy (DC + 2) were cultured on selective media. Colonies of Enterobacteriaceae, group D streptococci, staphylococci, and Candida were counted. A moderate but significant (p less than 0.01) decrease in the Enterobacteriaceae count was seen, with a fall from 8 log 10 (4.8 to 9.4) on D0 to 6.4 (3.6-9) on D2, 6 (4.6-7.2) on D5 and 4.7 (2-8.2) on DC + 2. No cefixime resistant Entrobacteriaceae or Pseudomonas strains were evidenced. A slight, non significant decrease in group D streptococci counts was found, with values of 7.1, 7.1, 5.8, and 8.3 log 10 at the successive time points. All children exhibited fecal staphylococcal strains which were all coagulase-negative and which did not undergo noticeable quantitative changes (mean successive values were 2.5, 1.8, 3.5, and 3.8 log 10). Candida were found in four children and also changed little over time (mean successive values: 2, 1.7, 2, and 2.6 log 10). In sum, oral administration of cefixime was associated with a modest decrease in the number of Enterobacteriaceae, with no development of resistance to cefixime. PMID- 1495827 TI - [Bacteriostatic and bactericidal activities of cyclines, macrolides and fluoroquinolones against Chlamydia trachomatis]. AB - The in vitro activity of minocycline, doxycycline, erythromycin, roxithromycin, spiramycin, pefloxacin, and ofloxacin against ten C. trachomatis strains recovered from human genital tract specimens was evaluated. Mac Coy cell monolayers in 24-microwell plates were used. The C. trachomatis inoculum was 10(4) IFU/well. Appropriate dilutions of antibiotic were added and inclusions were detected by immunofluorescence using monoclonal antibodies. MICs were determined after 48 hours of exposure to each antimicrobial. The MIC90 for cyclines was 0.2 mg/l. Among tested macrolides, roxithromycin had a lower MIC than erythromycin (0.2 versus 0.4 mg/l) whereas spiramycin inhibited growth only in a concentration of 2 mg/l. Ofloxacin showed better activity than pefloxacin. Bactericidal activity was evaluated by determining two parameters: MBC1 (without transfer to new cells) measured the ability of a C. trachomatis particle to persist in a latent form within cells exposed to an antibiotic and to grow again following removal of the antibiotic, whereas MBC2 (with transfer to new cells) reflected infectivity of the bacteria after 48 hours exposure to the antimicrobial. None of the tested antibiotics was bactericidal according to both parameters. The ability of C. trachomatis to remain within antibiotic-exposed cells in a latent form was clearly demonstrated by the high MBC1 values. This feature may explain why recurrences are common in clinical practice. PMID- 1495829 TI - [Antibiotic sensitivity of forty-four strains of group EF4 bacteria: study of minimum inhibitory concentrations using the agar dilution method]. AB - EF4 bacteria are found in animal saliva and may contaminate bite wounds. Minimum inhibitory concentrations of 36 antimicrobials against 44 EF4 strains were determined using dilution in Mueller-Hinton agar. EF4 bacteria were susceptible to aminopenicillins, carboxypenicillins, ureidopenicillins, third-generation cephalosporins, fluoroquinolones, rifampicin, and trimethoprime-sulfamethoxazole. Susceptibility was intermediate for penicillin G, low for macrolides and variable for aminoglycosides. EF4 bacteria were resistant to lincomycin and trimethoprime. Routine prophylactic treatment of bite-induced Pasteurella infections using an aminopenicillin or a cycline also protects against EF4 infection of the wound. PMID- 1495828 TI - [In vitro kinetics of the activity of fusidic acid and fluoroquinolones combinations against staphylococci according to methicillin-resistance phenotype. Implications for the treatment of osteoarticular infections]. AB - The kinetics of the effect of fusidic acid and of two fluoropiperazinyl quinolones (ofloxacin and pefloxacin), used alone or in combination, on ten methicillin-susceptible or methicillin-resistant strains of staphylococci were studied. Little or no bactericidal effects were seen with fusidic acid. With ofloxacin and pefloxacin, the bactericidal effect was delayed and occurred only with high concentrations. Used in combination, fusidic acid and the fluoroquinolones exhibited no synergistic effects and occasionally antagonized each other in vitro. The methicillin-resistance phenotype of organisms had no influence on results. PMID- 1495830 TI - [In vitro sensitivity to antibiotics of genital mycoplasmas isolated in Toulouse. Study of new molecules (macrolides and quinolones)]. AB - The minimal metabolism-inhibiting concentrations (MMC) of 11 antibiotics were determined for 40 strains each of M. hominis and U. urealyticum using a terminal color change broth method. All strains were recovered in 1990. Resistance to tetracycline (MMC greater than 8 mg/l) was found for 12.5% of strains of M. hominis and U. urealyticum, as compared with 5% in 1985. Rokitamycin was the most active macrolide against M. hominis (MMC 90: 0.06 mg/l). U. urealyticum strains were susceptible to all the macrolides tested, with the greatest activities being seen for rokitamycin and clarithromycin (MMC 90: 0.06 mg/l and 0.12 mg/l respectively). Sparfloxacin was the most active quinolone against both species. Human clinical trials designed to evaluate these new molecules for the treatment of mycoplasmal and ureaplasmal genital infections are warranted. PMID- 1495831 TI - [Bacteriostatic activity and killing curves of eight antibiotics against seven strains of penicillin G-resistant pneumococci]. AB - Increasing resistance to multiple antimicrobial agents including penicillins is a current problem with Streptococcus pneumoniae. Seven cases of severe infection due to penicillin G-resistant pneumococci were seen in two teaching hospitals in Paris (France) during the first half of 1991; six of the strains were recovered from pulmonary secretions (protected brush specimens) and one from cerebrospinal fluid (CSF). The bacteriostatic activity and killing curves of eight antimicrobials against these seven strains were studied. Antimicrobial agents tested included penicillin G (PEN), amoxicillin (AMX), cefotaxime (CTX), imipenem (IPM), rifampin (RIF), vancomycin (VAN), fosfomycin (FOS), and erythromycin (ERO). MICs were determined using the agar dilution method. Killing curves were obtained using a liquid medium inoculated with 10(5) to 10(6) CFU/ml and subjected to continuous agitation; survivors were counted at baseline and after 1, 3 and 5 hours incubation. MICs of each antimicrobial (mg/l) for the seven strains were in the following ranges: PEN: 0.5-2, AMX: 0.5-2; CTX: 0.125-1; IPM: 0.03-0.25; RIF: 0.12-0.25; VAN: 0.25-1; FOS: 16; ERO: 0.06 greater than 4. Overall, bactericidal activity was greatest with vancomycin, followed by imipenem, then amoxicillin. The cefotaxime-fosfomycin combination proved synergistic and exhibited bactericidal activity (2MIC + 2MIC) for three of the seven strains. This study demonstrated the value of the cefotaxime-fosfomycin combination. Both these antimicrobials seem appropriate for the treatment of meningitis caused by penicillin G-resistant pneumococci provided their dosage is adjusted to achieve adequate drug levels in the cerebrospinal fluid. PMID- 1495832 TI - [In vitro evaluation of the activity of butoconazole against Trichomonas vaginalis]. AB - An in vitro study was carried out on ten first clinical isolates of Trichomonas vaginalis. Increasing levels of butaconazole were added to 150 microliters of a dilution in Roiron medium adjusted to 50,000 Trichomonas/ml. Results were read after 1, 2, 6 and 24 hours aerobic incubation at 37 degrees C. Minimum lethal concentration was 93 micrograms/microliters after one hour, 23 micrograms/microliter after six hours and 12 micrograms/microliters after 24 hours. These findings warrant in vivo studies of butoconazole against Trichomonas. This drug, which has already been proved effective in fungal infections, may prove very useful since concomitant infection of the genital tract by Trichomonas and Candida is common. PMID- 1495833 TI - [Comparative study of two systems for the determination of the sensitivity of yeasts to antifungal agents]. AB - One hundred yeast strains (including 60 Candida albicans) were tested in two laboratories using two different antifungal susceptibility test kits, ATB Fungus and Mycostandard. Tests were carried out under everyday work conditions. Four antifungal agents were compared: amphotericin B, flucytosine, miconazole, and ketoconazole. Results were discrepant in 19.2% (77/400) of cases. Following retesting of discordant cases with both kits, the agreement rate for strain characterization was 95.5%. Few discrepancies were seen with flucytosine. Conflicting results obtained with amphotericin B were due to poor reproducibility of Mycostandard results, especially for species other than C. albicans. In contrast, reproducibility of the ATB Fungus kit was inadequate for miconazole. The rate of discrepant results was greatest for ketoconazole. Intermediate susceptibility was seen more often with ATB Fungus for C. albicans and with Mycostandard for C. glabrata and C. krusei. The lack of reproducibility under routine working conditions should lead gallery manufacturers to strive to achieve clearer readings. PMID- 1495834 TI - [In vitro evaluation of the sensitivity to fluconazole of different species of yeasts isolated in pathology]. AB - In a previous study, the authors developed a technique for evaluating the in vitro susceptibility (or resistance) of Candida albicans to fluconazole, using casitone broth and agar. Photometric readings of growth in liquid media proved more accurate for evaluating antifungal activity and consistently agreed with clinical findings in all studied cases. This method was consequently extended from C. albicans to other yeasts recovered from high-risk patients (C. glabrata, C. famata, C. tropicalis, C. krusei, C. pseudotropicalis, C. parapsilosis, etc...). High resolution antifungal assay medium (broth and agar) and casitone medium (broth and agar) with or without agitation (Autobac System) were used to study the activity of fluconazole against approximately one hundred yeast strains. MICs above 3.12 micrograms/ml were found for several strains, particularly belonging to the C. glabrata and C. krusei species. These values are equal to or greater than serum levels achieved during treatment with fluconazole, a fact which raises practical questions concerning fluconazole therapy and may explain the failure of fluconazole to eradicate yeasts in some patients. PMID- 1495835 TI - [Emulsion of amphotericin B in Intralipid 20%: in vitro and in vivo efficacy]. AB - Toxic effects limit the use of amphotericin B (AmB) for the treatment of systemic Candida infections. In vitro and in vivo toxicity can be substantially reduced by mixing AmB with a lipid emulsion used for parenteral nutrition, intralipid 20% (IL). This study was designed to evaluate the potential effects of IL on the activity of Amphotericin B against Candida. A clinical strain of Candida albicans was used. AmB deoxycholate (Fungizone) was reconstituted in a 5% glucoce solution (AmB-G5), in 3 mg/ml IL (AmB-IL3) or in 1.5 mg/ml IL (AmB-IL 1.5). Minimum inhibitory concentrations and minimum lethal concentrations were 0.4 mg/l and 2.5 mg/l, respectively, with AmB-G5, 0.1 mg/l and 1 mg/l with AmB-IL3, and 0.24 mg/l and 1 mg/l with AmB-IL 1.5. In vitro killing curves with 0.1 mg/l, 0.25 mg/l, and 2.5 mg/l AmB were determined with the following results: 1) with 0.1 and 0.25 mg/l AmB, fungicidal activity was seen with AmB-IL3 and AmB-IL 1.5 but not with AmB-G5; 2) with 2.5 mg/l AmB, fungicidal activity was less marked with AmB-G5 ( 1.7 log CFU/ml after 24 hours) than with AmB-IL3 and AmB-IL1.5 (-4.3 log CFU/ml and -4.2 log CFU/ml, respectively, after 24 hours; p less than 0.05). In rabbits given a single intravenous injection of 4 mg/kg AmB, analysis of infected subcutaneous fibrin clots detected measurable concentrations of AmB beyond the 24th-36th hour, with levels of 0.5 mg/l for AmB-G5 and 1 mg/l for the two AmB-IL preparations over a period of three days.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1495836 TI - [Treatment and secondary prophylaxis with fluconazole for oropharyngeal candidiasis in HIV-positive patients. A mycological analysis of failures]. AB - This prospective study evaluated the in vitro susceptibility of Candida albicans isolates recovered from the oral cavity of AIDS/ARC patients before and during long-term therapy with fluconazole. Thirty adults (15 with ARC and 15 with AIDS) with a first episode of thrush candidiasis were given oral fluconazole (Triflucan 50 mg; one capsule daily) for at least three months. Fungal susceptibility testing was performed before treatment, after one month, and at last follow-up (range 3.5-12 months; mean 5.7 months). MICs were determined using the agar dilution method with casitone (Difco 259-01) as the test medium at pH 7.2-7.4. There were two initial clinical failures (one with high MICs before and under treatment and one with an intermediate MIC initially and a rise in MIC under fluconazole). Four patients developed a clinical relapse with no change in MICs (which were low or intermediate). In six patients, clinical symptoms resolved but carriage of C. albicans persisted (low MICs). In 18 patients, clinical resolution with eradication of C. albicans was achieved. These data suggest that (1) clinical failures may be associated with in vitro resistance; (2) relapses under fluconazole maintenance therapy may develop in patients with advanced HIV disease despite the lack of change in the susceptibility of strains. PMID- 1495837 TI - [Comparison of the activity against Streptococcus mutans of a chlorhexidine-based antiseptic as a suspension or as a biofilm]. AB - When bacteria colonize a surface they form a biofilm whose susceptibility to anti microbials is different from that of the same bacterial species forming a homogeneous suspension in a liquid. This study investigated colonization of an inert solid phase (Tygon) with Streptococcus mutans ATCC 25,175--one of the strains involved in the initiation of cariogenic dental plaque--in a continuous flow of fresh medium sufficiently diluted so as to preclude growth of suspended bacteria. Only those bacteria which adhered to the solid phase grew, forming a biofilm. The antiseptic activity of Eludril (0.1% chlorhexidine) on this biofilm under dynamic (flowing medium) and static (stagnant medium) conditions was studied by comparison with the same strain in a suspension (in compliance with the AFNOR NF T 72-150 norm) and in a confluent culture on a filtering membrane. The biofilm was less susceptible under dynamic than under static conditions; under both conditions, the biofilm was less susceptible than the suspension. According to this model, the concentration of antiseptic recommended by the manufacturer according to studies using AFNOR norm NF T 72-150 (bacteria in a suspension) may be inadequate for bacteria adhering to tooth surfaces or gingival mucosa. PMID- 1495838 TI - [Kinetics of bactericidal and sporicidal effects of a disinfectant against bacteria isolated from hospital units]. AB - The bactericidal and sporicidal activities of a peracetic acid disinfectant commonly used in hospitals (Acetoper 200) was studied using three bacterial species recovered in water from hemodialysis machines and humidifiers, i.e., Pseudomonas aeruginosa, Serratia liquefaciens, and Bacillus subtilis (spores). The method used was derived from AFNOR norms NF T 72-151 and NF T 72-231. For each strain, three concentrations of disinfectant were tested. Counts were performed every five minutes for one hour to evaluate killing kinetics. For both Gram-negative organisms, survival curves were biphasic, whereas B. subtilis counts decreased logarithmically. Both concentration and time influenced the 5 log10 decrease in counts. With S. liquefaciens and B. subtilis (spores), the 5 log10 decrease was not reached with low levels of disinfectant. In every case, the D value decreased substantially with increasing levels of disinfectant. PMID- 1495839 TI - [Study of intraocular diffusion of ofloxacin in humans and rabbits]. AB - The diffusion of ofloxacin in infected and healthy human and rabbit eyes was investigated. In the human study, cataract surgery patients were given intravenous ofloxacin either as a single 200 or 400 mg dose or as two 400 mg infusions 12 hours apart. Samples of aqueous humor and plasma were collected between 1 and 12 hours after the end of the infusion. Levels in the anterior chamber increased with the dose; peak levels, which occurred after three hours, were 0.33 mg/l after 200 mg and 1.24 mg/l after two 200 mg doses given 12 hours apart. In the rabbit study, 16 hours after experimental infection of the left eye by injection of S. epidermidis into the vitreous, animals were given an intraperitoneal injection of 20 or 50 mg/kg ofloxacin. Dosages in the various ocular tissues showed that penetration into the eye varied with race (albinos greater than pigmented) and dose. Intraocular ofloxacin levels, including in the vitreous, increased two fold when the eye was infected; however, penetration into the sclera, choroid, and retina was comparable in infected and noninfected eyes. These findings in humans and animals suggest that ofloxacin in a dose of a least 400 mg is a useful agent for the treatment of prophylaxis of ocular infections. PMID- 1495840 TI - [Diffusion of piperacillin in the eye]. AB - Intraocular diffusion of piperacillin was studied in 42 patients scheduled for cataract surgery (n = 35) or vitrectomy (n = 7). Piperacillin was administered intravenously (4 g/injection). Thirty-four patients were given a single dose and 8 were given two doses 12 hours apart. Peak piperacillin levels in the aqueous (7.3 mg/l) occurred one hour after the injection; levels in the vitreous were low (less than 0.6 mg/l). Intraocular diffusion of piperacillin was also studied in rabbits with an experimental Staphylococcus epidermidis infection of one eye; the other eye served as the control. In pigmented rabbits (6 Fauve de Bourgogne animals), increased diffusion and decreased elimination of piperacillin were seen in the aqueous, iris and cornea of the infected eyes, as compared with uninfected control eyes. In albino rabbits (6 New Zealand animals), results were less conclusive, with a difference between the infected and healthy eyes appearing only during the second hour following the injection. The good diffusion of piperacillin in the aqueous, especially in infected eyes (at least in rabbits), suggests that this drug may be useful for the treatment of ocular infections provided it is initiated early and given in combination with another antimicrobial exhibiting good intraocular diffusion. PMID- 1495841 TI - [Biliary excretion and hepatic disposal of cefixime: experimental and clinical study]. AB - Cefixime is a new oral cephalosporin with in vitro activity similar to that of third-generation cephalosporins. Renal excretion accounts for only 40% of systemic clearance of cefixime, suggesting that biliary excretion of the drug may be significant. This study was designed to determine to what extent nonrenal clearance of cefixime is due to biliary excretion of the parent compound. In an isolated perfused rabbit liver model, biliary excretion of cefixime was very low, with only 0.28 +/- 0.15% of a single 10 mg dose injected in the system being recovered in the bile after three hours perfusion. The liver biotransformation rate for cefixime was found to be 16.2%. These results are in striking contrast with those obtained in human studies. Cefixime levels in duodenal juice aspirates collected over four hours following an intravenous injection of 200 mg cefixime in six healthy volunteers were at least fivefold concomitant serum levels. Studies of bile collected by external biliary drainage during 24 hours following an oral dose of 200 mg cefixime in ten cholecystectomized patients showed that the Cmax was 56.9 +/- 70 mg/l, i.e., 25-fold the serum Cmax (2.3 +/- 0.85 mg/l). The bile AUC/serum AUC ratio was 20.4 +/- 20.3. Mean bile level of cefixime was still as high as 4.3 +/- 3.7 mg/l 20 hours after dosing. The amount of cefixime excreted in the bile over 24 hours was 10.0 +/- 12.3 mg i.e., 5% of the dose administered. Twenty-four hour renal excretion of cefixime was 53.3 +/- 26.2 mg.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1495842 TI - [Pulmonary and bronchial kinetics of cefuroxime after a single 500 mg intramuscular injection]. AB - Thirty-two patients (28 males; mean age 56 +/- 10 years) who were undergoing bronchopulmonary exeresis surgery were included in this study of the pulmonary (pulm), bronchial (br), and plasma (pl) kinetics of cefuroxime after a single 500 mg intramuscular injection. Twenty-nine bronchial specimens and 38 pulmonary and plasma specimens were taken on average at the following times after the cefuroxime injection: 1 h, 2 h, 3 h, 4 h, 6 h, 8 h, and 10 h. Cefuroxime was assayed using HPLC on ground tissues, with a correction for contamination by blood. Peak concentrations (C) were found after one hour (Cpl = 11.6 +/- 0.8 micrograms/ml; Cpulm = 7.3 +/- 3.3 micrograms/g; Cbr = 3.7 +/- 1.5 micrograms/g) with the following residual values after 8 hours: Cpl = 0.94 +/- 1.04 micrograms/ml, Cpulm = 0.49 +/- 0.45 micrograms/g, Cbr = 0.15 +/- 0.07 micrograms/g (means +/- 1 SD). Elimination kinetics were monoexponential and similar in plasma, lung tissue and bronchial tissue (elimination half-lives: 1.74 h, 1.66 h, and 1.56 h, respectively), suggesting that all three elements belong to the same pharmacokinetic compartment. Mean intrapolated area-under-the-curve values (AUC) were 33.58 micrograms.ml-1.h (plasma), 20.08 micrograms.g-1.h (lung), and 10.22 micrograms/g-1.h (bronchus). The AUCpulm/AUCpl and AUCbr/AUCpl ratios were 0.60 and 0.30, respectively, in agreement with mean values of tissue level/simultaneous plasma level ratios (lung: 0.59; bronchus: 0.33). PMID- 1495844 TI - [Resistance to antibiotics of vibrio cholerae strains isolated in Angola]. AB - Among 87 strains of Vibrio choleare (78 Ogawa serotype and 9 Inaba serotype strains) isolated in Angola in 1987-1990, 86% exhibited multiple resistance to antimicrobials. Eighty-four to 86% of strains were resistant to ampicillin with beta-lactamase production (MIC greater than or equal to 512 mg/l), streptomycin (MIC greater than or equal to 64 mg/l), spectinomycin (MIC greater than or equal to 1,024 mg/l), and trimethoprime-sulfisoxazole (MIC greater than 1,024 mg/l). Seventy-four per cent of strains were resistant to kanamycin (MIC = 512 mg/l), 26% to chloramphenicol (MIC = 32 mg/l), 10% to tetracycline (MIC = 16 mg/l), and 10% to gentamycin (MIC greater than or equal to 32 mg/l). Transfer to E. coli K12 was associated with a substantial increase in expression of resistance to tetracycline and chloramphenicol (CAT type I), with MICs in the 128-512 mg/l range. Transfer rates to E. coli K12 of plasmids for the various resistance phenotypes were 10(-6)/10(-8). The size of the isolated plasmids was 100 Md in diameter and belonged to the incompatibility group inc 6-C. PMID- 1495843 TI - [Detection of extended-spectrum beta-lactamases by the rapid ATB E technique. Value of the API V2.1.1 expert system]. AB - Twenty-two extended-spectrum betalactamase-producing strains of enterobacteriaceae recovered in the authors' hospital were tested using the Rapid ATB E coupled with the API V2.1.1. expert system. The expert system detected 90.9% of ESBL-producing strains. Two strains producing a SHV2 and a CTX1, respectively, escaped detection by the expert system despite concomitant resistance to aminoglycosides. PMID- 1495845 TI - [Spread in hospital units of a Pseudomonas aeruginosa phenotype producing a beta lactamase highly inducible by clavulanic acid in vitro]. AB - Pseudomonas aeruginosa strains belonging to the serogroup O:11 exhibiting susceptibility to ticarcillin (TIC) and resistance to the ticarcillin-clavulanic acid (CA) combination were found in 19 inpatients over a 14 month period. Mean inhibition diameters obtained using the agar diffusion method were 21.75 mm around the TIC disks (75 micrograms) and 15.96 mm around the TIC+CA disks (75 + 10 micrograms). With control PaO:11 strains, these diameters were 25.27 and 25 mm, respectively. MIC for ticarcillin determined using the checkerboard method rose to 64 mg with CA levels of 16 mg/l or more. CA exhibited dose-dependent antagonism on TIC killing curves when TIC levels approximated the MIC; this effect was no longer present with higher TIC levels. In the crude bacterial extract, a betalactamase of the cephalosporinase type was detected in the absence of induction and increased threefold after exposure to cefoxitin (100 mg/l) and fourfold after exposure to CA (5 mg/l). All these PaO:11 strains exhibited the same antimicrobial resistance phenotype with decreased susceptibility to ureidopenicillins and resistance to aminoglycosides and fluoroquinolones. The induction of a chromosome-encoded cephalosporinase by CA proved useful as an epidemiologic marker. Nosocomial spread of this phenotype was likely the result of selection due to use of antimicrobials. PMID- 1495846 TI - [Resistance to antibiotic treatment produced in a model of experimental Pseudomonas aeruginosa peritonitis]. AB - A mouse model of experimental Pseudomonas aeruginosa peritonitis was used to evaluate the emergence of resistant mutants during antimicrobial therapy. Mice were infected intraperitoneally with a large inoculum (10(8) CFU + 125 mg talcum) of one of eight strains of Pseudomonas aeruginosa and treated for eight hours with imipenem (IPM) (2 mg/kg/60 min), ciprofloxacin (CIP) (5 mg/kg/45 min), ceftazidime (CAZ) (2 mg/kg/45 min), and amikacin (AN) (2 mg/kg/45 min), alone or in combination. Dosages were selected to achieve and maintain for 8 hours intraperitoneal concentrations similar to those seen in human bronchial secretions. Emergence of resistant strains occurred in 88% of mice after IPM, 29% after CIP, and 31% after CAZ. MICs for resistant strains were increased 8-fold to 512-fold above baseline. Given in combination, IPM and CIP use was followed with lower rates of resistance to each drug (6% and 2% respectively) than use of each antimicrobial alone (p less than 0.001). Combination with amikacin reduced resistance rates for all the antimicrobials studied. No resistant strains occurred with the CIP-CAZ combination. Under the experimental conditions used, the CIP-CAZ combination provided the best results, although the difference with the CIP-IPM combination was not statistically significant. PMID- 1495847 TI - [Epidemiology of Chlamydia trachomatis using analysis of gene encoding of the major outer membrane protein]. AB - One hundred and eight clinical strains and 24 reference strains of C. trachomatis were typed using differential restriction mapping of omp1, the gene which encodes the major outer membrane protein. The gene was obtained by polymerase chain reaction (PCR). This molecular typing method correlated well with serological typing. Eighty-four per cent of clinical strains were typed using the enzyme AluI alone. Heterogeneity was looked for among the most common serovars (E, F, and D; 62%, 17%, and 9%, respectively). Analysis of the PCR-amplified fourth variable domain of omp1 using denaturing gradient gel electrophoresis followed by direct sequencing of the variants disclosed substantial heterogeneity within the D serovar. Conversely, serovars E and F were homogeneous, with however a single variant strain of serovar E. PMID- 1495848 TI - [Characterization of Alcaligenes species using analysis of esterase electrophoretic polymorphism and analysis of antibiotic resistance profiles]. AB - The species of an Alcaligenes bacterial strain may be difficult to determine on the basis of conventional phenotype features. Esterase pattern analysis using acrylamide-agar gel electrophoresis and determination of the antimicrobial resistance profile (agar diffusion method) were performed for A. faecalis (34 strains). A. denitrificans subsp xylosoxydans (16 strains) and A. piechaudi (5 strains). The Cistat program (D2 Software) was used for statistical representation of results. The homogeneous, species-specific esterase patterns ensured correct assignment of each strain to one of the three species. Antimicrobial susceptibility was greatest for A. faecalis which was susceptible to both cephalosporins of all generations and aminoglycosides. A. xylosoxydans was the species with the greatest resistance to antimicrobials. A. piechaudii exhibited intermediate susceptibility. PMID- 1495849 TI - [Peripheral blood cells secreting specific antibodies after oral stimulation with a ribosomal vaccine]. AB - This investigation was designed to investigate mechanisms underlying oral immunization in humans after ingestion of the ribosomal vaccine D53. Immunofluorescence and ELISA (Enzyme-Linked ImmunoSorbent Assay) spot techniques were used for peripheral blood studies. The first part of the investigation was a double-blind placebo-controlled study of 12 healthy volunteers; counts of cells containing immunoglobulins and cells producing specific antibodies were higher in the individuals given the oral ribosomal vaccine than in the placebo-treated controls. In the second part of the investigation, analysis of the kinetics of apparition of the immunoglobulin-containing and specific antibody-producing cells suggested prompt stimulation of Peyer patch B lymphocytes following ingestion of the vaccine. Lastly, a study of 5 children given the vaccine on a long-term basis demonstrated increased counts of both above-described cell types after one month treatment. PMID- 1495850 TI - [Approach to the study of suicide in the essays of Enrico Morselli (1879) and in the successive hypotheses of Durkheim and Freud]. AB - Scientific investigations on suicide began at the beginning of the XIX century. The aim of such investigations was the evaluation of the epidemiological and statistical distribution of the phenomenon in order to set up preventive intervention, as well as the establishment of the psychological and psychopathological characteristics of the subjects choosing this solution to their life. E. Morselli's work on the matter (1879) can be considered the main Italian contribution to the discussion that was troubling and antagonizing the most competent authors in all the civil world from the half a century and it was regarded in due consideration by his contemporaries too. The second author taken into consideration is E. Durkheim, whose monograph issued twenty years later presents elements having such originality and accuracy that they represent even today a constant reference for the suicide studies. S. Freud, on his side, did never write any monograph on this matter, but fundamental observations on the self-suppression psychodynamic interpretation can be found in his works. PMID- 1495851 TI - Malignant primitive neuroepithelial tumour of soft tissues mimicking a cellular ependymoma. AB - A malignant small blue-cell soft tissue tumour in a 13 year-old girl is reported. By light microscopy the tumour showed prominent pseudo-rosettes suggesting peripheral neuroepithelial tumour (PNET) with ependymal differentiation or extraspinal cellular ependymoma. Ultrastructural and immunocytochemical findings helped in excluding an ependymal neoplasm (low-grade malignancy) and supported the diagnosis of malignant primitive PNET mimicking a cellular ependymoma (high grade malignancy). PMID- 1495852 TI - [Human dirofilariasis: discovery of a gravid female of Dirofilaria repens in a subcutaneous nodule]. AB - A case of human subcutaneous dirofilariasis occurred in a 53 years old woman from Scafati (Salerno province). It was localized in the left submammary region. The patient was operated 16 years ago for a papillary carcinoma of the thyroid. For this reason a metastasis was clinically suspected. The histological examination revealed the presence of a granulomatous nodule formed around a Dirofilaria repens gravid female in the subcutaneous tissue. The presence of microfilariae in the uterus of the nematode would suggest that also a mature male was present at the same time in the patient, although it was not possible to localise it. Haematic eosinophilia was observed. PMID- 1495853 TI - Cardiopulmonary response to exercise in anorexia nervosa. AB - Malnutrition is associated with a number of systemic diseases that are often accompanied by severe exercise limitation. Anorexia nervosa (AN) is a disease characterized by malnutrition due to psychological factors rather than systemic disease. Diminished exercise capacity in AN has been attributed to a loss of muscle mass, dysfunction of remaining muscle, and impaired cardiovascular responses. In order to evaluate the role of malnutrition in the cardiopulmonary response to exercise, nine adolescent girls with AN were evaluated during progressive and steady-state exercise testing using a cycle ergometer. Nutritional status was assessed by body mass percentile (BMP) and percent ideal weight (PIWT). Cardiac output was measured by the indirect (CO2 rebreathing) Fick method. Maximum work capacity (Wmax) was expressed as a percent of predicted for sex and height, and cardiac output as a percent of predicted for oxygen consumption. To ensure that the laboratory values were comparable to the predicted values, a control group consisting of ten adolescents was studied concurrently. Wmax was below the 95% confidence interval in six of nine of the AN group (mean +/- SD: 70 +/- 22% predicted), whereas two of ten controls were below and one above this interval (112 +/- 37%). Wmax correlated with nutritional status (BMP: r = 0.75; P less than 0.001; PIWT: r = 0.8, P less than 0.001). Ventilatory responses for CO2 production at steady state and for Wmax were appropriate in both groups. Cardiac output was appropriate in both the controls (103 +/- 12%) and the AN group (104 +/- 14%).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1495854 TI - High-frequency jet ventilation and surfactant treatment of newborns with severe respiratory failure. AB - Twenty-eight newborn infants (birthweight, 2.4 +/- 1.1 kg; gestational age, 34.6 +/- 6.1 weeks) with respiratory distress syndrome (RDS), meconium aspiration syndrome, or pneumonia who deteriorated in spite of optimal conventional mechanical ventilation (CMV) and exogenous surfactant therapy were treated with high-frequency jet ventilation (HFJV) and continued surfactant therapy. For enrollment, infants had to have a limited response to surfactant therapy and conventional ventilation, and meet clinical criteria that confirmed clinical deterioration and severity of illness. Study infants had received exogenous calf lung surfactant extract (CLSE) and conventional ventilation prior to the start of HFJV at 46.3 +/- 8.2 hours of age. Patients initially responded to HFJV alone with significant improvement in several respiratory variables, but deteriorated subsequently and receive additional doses of exogenous surfactant on HFJV. Exogenous surfactant and HFJV resulted in significant and sustained improvement in several respiratory variables. Only ten patients deteriorated to meet criteria for a second surfactant dose on HFJV, and two patients received a third dose. Twenty-five of the 28 patients studied survived (89%). No patients received extracorporeal membrane oxygenation or were discharged home on oxygen. The results of this pilot study suggest that the combination of HFJV and exogenous surfactant replacement may be effective in treating infants with more severe respiratory failure, and indicate the need for more extensive controlled investigations. PMID- 1495855 TI - Cardiorespiratory effects of changing inspiratory to expiratory ratio during high frequency oscillation in an animal model of respiratory failure. AB - To examine the effects of varying inspiratory/expiratory ratio (I/E) on cardiorespiratory function during high-frequency oscillation (HFO), 11 saline lavaged rabbits were ventilated at I/E = 1:2, 1:1.5, 1.5:1, and 2:1 in a paired comparison to a baseline of I/E = 1:1. HFO was delivered by a SensorMedics model 3100 oscillator at a frequency of 10 Hz. Pressure amplitude and proximal mean airway pressure (PPaw) were held constant as I/E was varied from baseline to the experimental I/E. During each paired observation, PaO2, PaCO2, cardiac output, blood pressure, and distal mean airway pressure (DPaw) were measured. We found that as I/E was increased or decreased from 1:1, no significant changes in PaO2, PaCO2, blood pressure, or cardiac output occurred. We conclude that in this model, varying I/E has no significant effect on oxygenation, ventilation, or cardiovascular function. PMID- 1495856 TI - A bench test evaluation of a neonatal closed tracheal suction system. AB - We tested the hypothesis that a possible mechanism for reduced hypoxia during suctioning with closed tracheal suction systems (CTSS) is the provision of uninterrupted gas delivery and the maintenance of airway pressures. This was accomplished by using a neonatal ventilator and test lung model to permit the insertion of a CTSS (with and without suction applied), measurements of inspiratory and end-expiratory airway pressures proximal and distal to the endotracheal tube (ETT) and measurements of inspired and expired tidal volumes (sampled distal to the ETT). An 8 Fr CTSS was evaluated with 4.5, 4.0, and 3.5 mm ETT, and a 6 Fr CTSS with a 3.5, 3.0, and 2.5 mm ETT. We found that catheter placement without suction caused no changes in proximal airway pressures but distal peak inspiratory pressures decreased as the relationship between suction catheter size and ETT lumen increased, while distal end-expiratory pressures were unchanged. Similarly, distal tidal volumes progressively decreased as the size of the suction catheter occupied more of the ETT lumen. During suctioning with the 6 Fr catheter, proximal airway pressures were virtually unchanged; however, as ETT size decreased, distal airway pressures also decreased. The application of suction only modestly augmented the substantial decrement in measured tidal volumes when compared to catheter insertion alone. For the 8 Fr catheter, suction markedly reduced both proximal and distal airway pressures and tidal volumes. We conclude that the use of the CTSS tested in this neonatal ventilator/test lung model does not preserve continuity of volume or pressure delivery during suction procedures; therefore these cannot be the sole explanation for the reported reduction in suction related hypoxia. PMID- 1495857 TI - Progressive cyanosis in a child with hereditary hemorrhagic telangiectasia (Osler Weber-Rendu disease). PMID- 1495858 TI - On birthweight and compliance of the respiratory system as predictors of outcome in infants with respiratory failure. PMID- 1495859 TI - Airway responsiveness: new concepts and concerns. PMID- 1495860 TI - Dissociation of symptom scores and bronchial hyperreactivity: study in asthmatic children on long-term treatment with inhaled beclomethasone dipropionate. AB - The aim of the study was to evaluate the effects of inhaled steroids (IS) on the improvement of clinical asthma symptoms and on the decrease in bronchial hyperreactivity (BHR). Twenty-four children with severe asthma were given 1,000 micrograms beclomethasone dipropionate (BDP) daily and compared with ten asthmatic control children. The study included the evaluation of daily clinical score, of exercise induced asthma, of bronchial obstruction (forced expiratory volume in 1 sec, FEV1), and of BHR at months 0, 1, 2-3, and 4-5 (M0, M1, M2-3, and M4-5). BHR was assessed by standardized inhaled carbachol provocation measuring plethysmographic specific airway resistance (SRaw). The carbachol dose causing a 40% decrease in specific conductance (SGaw) was determined (PD40 SGaw). Clinical scores decreased at M1 (P less than 0.01) and throughout the study. FEV1 increased at M1 (P less than 0.05), M2-3 (P less than 0.01), and M4-5 (P less than 0.05) compared to M0. PD40 SGaw only increased significantly at M1 and M2-3. No individual correlation was found between clinical scores and PD40 SGaw at any testing, or between the decrease of clinical scores and the decrease of BHR. We conclude that bronchoconstrictive challenge tests do not adequately assess the clinical efficacy of IS. In clinical practice non-specific BHR should be preferentially measured for diagnosing atypical forms of asthma. PMID- 1495861 TI - The effects of airway hyperresponsiveness, wheezing, and atopy on longitudinal pulmonary function in children: a 6-year follow-up study. AB - We examined growth of spirometric lung function in 696 children of European ancestry who were followed from ages 9 to 15 years and stratified according to their degree of responsiveness to methacholine inhalation challenge, atopic status, and respiratory symptoms. Subjects were participants in the longitudinal Multidisciplinary Health and Development Study in Dunedin, New Zealand. Forced expired volume in 1 second (FEV1), and vital capacity (VC) were measured at 9, 11, 13, and 15 years of age, concurrently with assessment of airway responsiveness determined by the concentration of methacholine causing a 20% fall in FEV1 (PC20 FEV1). Atopic status was assessed at age 13 by skin-prick testing to 11 allergens. In children demonstrating airway hyperresponsiveness, FEV1 increased with age at a slower rate, and the FEV1/VC ratio had a faster rate of decline through childhood, compared to non-responsive children. Subjects with positive skin tests to house dust mite and cat dander also had lower mean FEV1/VC ratios than the control group. Any reported wheezing was associated with slower growth of FEV1 and VC in males. We conclude that in New Zealand children with airway responsiveness and/or atopy to house dust mite or cat growth of spirometric lung function is impaired. PMID- 1495862 TI - Elastase alpha 1-proteinase inhibitor and lactoferrin concentrations in endotracheal aspirates of ventilated newborns. AB - Bacterial colonization of the tracheo-bronchial tree is common and an established risk factor for infection in ventilated newborns. Elastase, a highly active proteinase, and lactoferrin, an iron-binding protein and potential modulator of the inflammatory process, are both major constituents of either azurophilic or primary granules of neutrophilic granulocytes, released by activation of these cells during the inflammatory response. Since both elastase, complexed with its major inhibitor alpha 1-proteinase inhibitor (E alpha 1-Pl), and lactoferrin (Lf) are indicators of granulocyte activation during bacterial infection, they may indicate infectious inflammation at the tracheobronchial site. To study whether these substances in a single suction probe may serve this purpose, we obtained 82 tracheo-bronchial aspirates routinely from 16 ventilated newborns with a median gestational age of 31.5 (range, 25-39) weeks for laboratory analysis and bacterial cultures. Systemic inflammatory response by differential white blood cell count and C-reactive protein (CRP) was monitored simultaneously. The median E alpha 1-Pl level was significantly elevated in culture-positive aspirates (1,005 micrograms/L; range, less than 30-29,240 micrograms/L) in contrast to culture-negative samples (158 micrograms/L; range, less than 30-1,408 micrograms/L). In addition to a diagnostic sensitivity of 77%, E alpha 1-Pl offered a high specificity of 88%, a positive predictive value of 97%, and a negative predictive value of 73%. In contrast, median Lf concentration (10.6; range, 0.3-58.3 mg/L vs. 11.7; range, 1.6-158 mg/L) showed no correlation with culture results. Of the culture-positive aspirates 36% corresponded with systemic signs of an acute inflammatory response, such as elevated I/T-ratio and CRP.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1495863 TI - Pediatric asthma deaths in Victoria: the mild are at risk. AB - Previous reviews of pediatric asthma mortality have mostly been from hospital based clinic populations and suggest that only those with severe asthma are most at risk. This report summarizes an investigation, by interviewer-administered questionnaire, into the circumstances surrounding the death in all patients aged 20 years or less who died from asthma in the State of Victoria over a 3 year period from May 1, 1986. During this period, 51 deaths due to asthma were reported. Thirty-three percent of these were judged to have a history of trivial or mild asthma, and 32% had no previous hospital admission for asthma. However, 36% were judged to have had severe asthma, 43% were taking regular inhaled beclomethasone or sodium cromoglycate, and 10% were taking regular oral steroids. Twenty-two percent had a previous admission to an ICU. Death occurred outside hospital in 40 (78%) subjects. In the final attack 63% had sudden onset and collapse within minutes, 12% were found dead, and 25% had acute progression of an established attack. The investigators assessed 39% of the deaths to have had potentially preventable elements. The preventable factors included: inadequate assessment or therapy of prior asthma (68%), poor compliance with therapy (53%), and delay in seeking help (47%). The majority of subjects in this survey could not be classified as "high risk." Therefore, clinicians should ensure that all young patients with asthma are aware of optimal maintenance management, can recognize deteriorating asthma, and follow a clear individualized crisis plan. PMID- 1495864 TI - Challenging, visionary, innovative. PMID- 1495865 TI - Women and AIDS: sociopolitical issues. AB - HIV infection and AIDS in women will continue without adequate diagnosis and treatment as long as women are not treated as full partners in society. Until issues related to women and their place in society are considered within the sociopolitical context, women who are at risk for HIV infection, those infected with the HIV virus, and those with AIDS will continue to receive inadequate attention. The National Center for Nursing's National Action Agenda, Nursing and the HIV Epidemic, provides some direction for addressing these issues and those that relate to practice, education, research, and health policy. It is incumbent on nurse researchers to conduct research related to the critical issues associated with HIV infection and AIDS in women, disseminate the findings of that research, and use those findings to inform and move health policy in this area forward. It is equally important to understand the issues that affect women- ethnic considerations, sexual practices, IV drug use--within the context or present political climate of our society. That climate allowed an NIH study that could identify risky sexual behaviors of adolescent and adult subjects who consent to participate in such a study to be called to a halt--not because of concerns about the study design or the scientific rigor of the study, but because of an elected official's fear that asking such questions will encourage these behaviors and his personal belief that such issues should not be discussed in polite society. These issues must be brought forward, acknowledged, and discussed if they are to be dealt with effectively. Otherwise, the relentless course of AIDS will continue.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1495866 TI - Nursing leadership in health policy decision making. PMID- 1495867 TI - Vernice Doris Ferguson: portrait in leadership. PMID- 1495868 TI - Empowering for professional, political, and health policy involvement. PMID- 1495869 TI - A framework for the transition from nursing records to a nursing information system. AB - The future of patient record keeping is being developed now. Critical aspects are in place with the development of computer communication standards for health care. The Institute of Medicine's report on the computerized patient record has galvanized many in the health care field to rethink their methods of record keeping. Nurses need to examine the history of the nursing record and look toward the development of a comprehensive nursing information system. Nurses, along with the other disciplines, must examine what they want the system of the future to encompass. A suggested framework for the information system has four major nursing components: (1) data storage component, (2) transaction log, (3) nursing decision support systems, and (4) an engine to link and combine the first three components and to present a consistent easy-to-use interface to the nurse. Done properly, this approach will reduce the amount of time nurses spend charting, add dimension to their notation, and increase the efficiency of data usage for clinical practice. The nursing information system must allow information availability in a manner that accentuates quality practice while releasing the nurse from time-consuming record keeping. These goals are possible to meet, but only if nurses plan for the design now, before it becomes a fait accompli. PMID- 1495870 TI - Factors affecting the use of nursing diagnosis. PMID- 1495872 TI - Experience the spectrum of oncology nursing. Third Annual Fall Institute, Oncology Nursing Society. Minneapolis, Minnesota, October 16-18, 1992. Program. PMID- 1495873 TI - Lipid metabolism in type II diabetes. AB - Hypertension, dyslipidemia, insulin resistance, and hyperinsulinemia- acknowledged risk factors for coronary artery disease--are all more common in persons with non-insulin-dependent diabetes than in nondiabetic persons. The interrelationships of these risk factors are becoming increasingly recognized. This article discusses the dyslipidemias commonly seen in type II diabetes and describes their relationship to glucose metabolism. PMID- 1495871 TI - Intervention studies in nursing: is the effect due to the independent variable? PMID- 1495874 TI - Office management of common anorectal problems. AB - Common anorectal problems can often be treated in the office setting. Hemorrhoids are usually relieved with use of bulk laxatives or stool softeners; if this fails, coagulation or rubber band ligation may be effective. Surgical therapy is still preferred for third- and fourth-degree hemorrhoids. Perirectal and perianal abscesses are treated by drainage, but in up to 30% of cases a fistula occurs following treatment. Surgical evaluation is appropriate when a fistula is suspected. Acute anal fissures often heal with conservative management; sphincterotomy may be needed for chronic fissures. Anal warts tend to recur and require several treatment sessions with use of ablative techniques. PMID- 1495875 TI - Relief from situational insomnia. Pharmacologic and other options. AB - Although most adults in the United States experience insomnia from time to time, many minimize the problem and fail to seek treatment. This occurs despite accumulating evidence that lack of sleep can seriously impair work performance, reflex response, cognitive abilities, and sense of well-being. Physicians should routinely inquire into a patient's sleep habits and be attuned to complaints of insomnia. A good working partnership between physician and patient may prevent complications of insomnia (eg, overconcern with the condition, demoralization, misuse of drugs and alcohol, disturbances of the circadian sleep-wake cycle), which might otherwise perpetuate and exacerbate the problem. Patients with situational insomnia can usually be treated by their primary care physician, who can offer thoughtful approaches to nonpharmacologic and pharmacologic treatment. In cases of chronic insomnia, referral to a sleep specialist or other authority may be advisable. PMID- 1495876 TI - The focused physical examination. Should checkups be tailor-made? AB - The "complete physical examination" taught in medical schools is not always the best approach to clinical assessment of asymptomatic adults. The authors of this article review the controversy surrounding the utility of routine physical examination, advocating evolution in medical practice from use of the complete physical examination toward the focused physical examination. PMID- 1495877 TI - Sudden death during exercise. A cruel turn of events. AB - The causes of sudden death in exercisers age 35 and younger are generally not preventable because they are typically structural and difficult to detect. The best a physician can do is be alert to important information in the family and patient history and to the occasional sign or symptom that may warrant further evaluation. For the over-35 exerciser, screening tests may be appropriate, especially if the person is just beginning an exercise program, although this remains an area of controversy. The screening tests available are far from perfect. If exercise testing is performed, the asymptomatic patient must be apprised of the possibility of a false-positive result and the consequences and attendant risks of overdiagnosis or additional testing (coronary angiography). Physicians should be alert to suspicious symptoms in physically active patients, but they should avoid the tendency to have these patients stop their exercise program. Instead, after appropriate diagnostic testing, they should advise a modified exercise program that is safely within the limits of the disease process involved. It is important to realize that physical activity can be a preventer of cardiac disease but also a provoker of sudden death. Even so, the benefits of regular exercise clearly outweigh the risk. PMID- 1495878 TI - Nephrotic syndrome in adults. A diagnostic and management challenge. AB - The adult with nephrotic syndrome presents diagnostic and treatment challenges for the primary care physician. Early consultation with a nephrologist is advisable to assist in choosing between empirical therapy or renal biopsy to identify the specific causative lesion. Some patients respond to treatment of either the specific disorder or the underlying cause. All patients should be afforded specific therapy, where available, and nonspecific therapy to minimize the severity of the nephrosis and attenuate the incidence and severity of complications. Although the cause of most disorders resulting in nephrotic syndrome remains unclear, active research into the syndrome's pathogenesis and treatment options should prove fruitful. PMID- 1495879 TI - The good and the bad about 11 healthcare plans. PMID- 1495880 TI - How to avert impending stroke. AB - Patients "lucky" enough to have a nondisabling transient ischemic attack as a warning sign of impending stroke deserve the best possible prophylactic treatment in an attempt to avert that catastrophe. Dr Edmeads provides a step-by-step discussion of diagnostic studies and therapeutic regimens that help avoid stroke in middle-aged and older patients who are at risk. PMID- 1495881 TI - Respiratory infections in children. What helps and what doesn't? AB - Respiratory disorders are common in children. Upper respiratory infection is particularly common in children who receive day care or group care. Frequently used methods of treating the common cold (eg, heated vapor, over-the-counter antihistamines and decongestants) have not been proven objectively to be beneficial in young children. Sinusitis is usually diagnosed through history taking (eg, complaints of more than 9 days of non-improving nasal congestion and/or cough), but radiographs may be necessary. Antibiotics effective against specific causative agents are the treatment of choice. Data do not support routine use of myringotomy to treat acute otitis media, but combined with tube placement, this method is useful for recurrent infection. Antibiotic prophylaxis may help prevent recurrent episodes of acute otitis media. Before tonsillectomy is considered for pharyngitis, a history of recurrent episodes must be documented. Epiglottitis, although increasingly rare, should still be considered when certain specific clinical signs are present. PMID- 1495882 TI - Amenorrhea and chronic anovulation. Finding and addressing the underlying cause. AB - Amenorrhea is a common problem with a complex etiology. However, the same diagnostic approach can be used in evaluation of all amenorrheic patients. Complete history taking and physical examination are important for determining the presence of congenital abnormalities and chronic conditions. Pregnancy is the most common cause of amenorrhea and should be ruled out in initial laboratory evaluation. Progesterone can then be given to assess endogenous estrogen production and the functioning of the uterus and vagina. Response to this hormone suggests the presence of ovarian, hypothalamic, or pituitary dysfunction, which can be confirmed with further testing. Lack of response to progesterone indicates hypoestrogenism or obstruction of the outflow tract. An estrogen-progesterone challenge helps differentiate these conditions. Chronic anovulation is the second most common cause of amenorrhea. Treatment of chronic anovulation is important to prevent the effects of unopposed estrogen stimulation of the endometrium and to reduce the risk of endometrial adenocarcinoma. PMID- 1495883 TI - Antiatherosclerotic effects of calcium channel blockers. AB - Hypertension is a constellation of abnormalities, including metabolic disorders. The current approach to treatment of hypertension should not be dictated solely by measures to lower blood pressure. It must also take into consideration the effect of antihypertensive drug treatment on the development of atherosclerosis and many other important factors. Evidence from rabbit models and cell cultures indicates that calcium channel blockers are antiatherogenic through a variety of mechanisms. In addition to preserving endothelial function, these agents inhibit the following: Platelet aggregation Migration of monocytes and smooth-muscle cells into the intima Incorporation of low-density lipoprotein cholesterol into these cells Matrix formation Calcium overload in atherosclerotic lesions However, additional studies are needed to delineate the antiatherogenic effects of these and other antihypertensive agents. PMID- 1495884 TI - Flexible sigmoidoscopy. PMID- 1495885 TI - Rational use of sulfonylureas. AB - The clinical use of sulfonylureas described in this article is both rational and effective for diabetic patients. Sulfonylureas are not used (1) in patients with insulin-dependent (type I) diabetes, because they are completely ineffective or (2) in patients with non-insulin-dependent (type II) diabetes who respond satisfactorily to diet, because they are unnecessary. In a patient with type II diabetes who has few or no symptoms but does not respond satisfactorily to diet, a sulfonylurea is introduced at a low dose, with gradual increases until a satisfactory response occurs, thus avoiding hypoglycemia. When symptoms of type II diabetes are marked, initiation of therapy with maximum doses of a sulfonylurea quickly distinguishes patients who need insulin therapy from those who have a good chance of responding to an oral drug. Abuse of sulfonylureas occurs when patients who could benefit from diet alone are treated with the drugs unnecessarily or, more often, when patients with poorly controlled disease continue to take maximum doses of the drugs. The usual situation is one in which the patient refuses insulin therapy or the physician does not suggest starting it. In other cases, the poorly controlled patient may be allowed to continue with a combination of a sulfonylurea and an ineffective dose of insulin. In this circumstance, the oral drug should be discontinued and insulin doses increased until control is more satisfactory. Because evidence is so compelling that near euglycemia has a beneficial effect on diabetic retinopathy, nephropathy, and neuropathy, physicians really do patients a disservice by misusing sulfonylureas. PMID- 1495886 TI - Combining insulin and sulfonylurea. A therapeutic option for type II diabetes. AB - Non-insulin-dependent (type II) diabetes mellitus is a progressive disease that requires sequential therapy to achieve optimal control. When diet and sulfonylurea fail to maintain glycemic control, the addition of a single daily injection of insulin may be indicated. The best candidates for this combined therapy are patients with typical adult-onset disease that has been present less than 10 to 15 years. PMID- 1495887 TI - Polyalkylcyanoacrylate nanoparticles as polymeric carriers for antisense oligonucleotides. AB - Adsorption of oligothymidylates on polyisobutyl- or polyisohexylcyanoacrylate nanoparticles was achieved in the presence of hydrophobic cations such as tetraphenylphosphonium chloride or quaternary ammonium salts. Results suggested that oligonucleotide adsorption on the nanoparticles was mediated by the formation of ion pairs between the negatively charged phosphate groups of the nucleic acid chain and the hydrophobic cations. The adsorption efficiency of oligonucleotide-cation complexes on nanoparticles was found to be highly dependent upon several parameters: oligonucleotide chain length, nature of the cyanoacrylic monomer, hydrophobicity of cations used as ion-pairing agents, and ionic concentration of the medium. Carrier capacity of polyisohexylcyanoacrylate nanoparticles for oligothymidylates (16 nucleotides) complexed with cetyltrimetylammonium bromide in the presence of 0.15 M NaCl was determined to be 5 mumol/g polymer. The in vitro protection of oligothymidylates adsorbed to nanoparticles against degradation by a 3'-exonuclease (snake venom phosphodiesterase) was also demonstrated. These results showed that nanoparticles can be considered as convenient carriers for the protection and delivery of oligonucleotides to cells in culture and for future applications in vivo. PMID- 1495888 TI - Correlation of in vitro release rate and in vivo absorption characteristics of four chlorpheniramine maleate extended-release formulations. AB - An in vitro/in vivo correlation was established for four formulations of chlorpheniramine maleate (histamine, H1-blocker) extended-release tablets exhibiting different in vitro release rate characteristics. In vitro release rate data were obtained for 12 individual tablets of each formulation using the USP Apparatus 2, paddle stirrer at 50 rpm in 1000 ml of distilled water at 37.0 +/- 0.5 degrees C. Inspection of the individual and mean release rate data indicated that the in vitro release rate of chlorpheniramine maleate was consistent with the intended design of the four extended-release formulations. The in vivo bioavailability and pharmacokinetics of these formulations were evaluated in 24 healthy subjects under fasting conditions. Wagner Nelson analyses of the in vivo data revealed extended release absorption profiles for all four formulations. Linear regression analyses of the mean percentage of dose absorbed versus the mean in vitro release resulted in a statistically significant correlation (r2 greater than 0.98, P less than 0.001) for each formulation. Qualitative rank order correlations were observed among all combinations of in vitro and in vivo parameters. These data support a Level A correlation between the in vitro release rate profiles and the in vivo absorption for chlorpheniramine maleate determined under fasting conditions. PMID- 1495889 TI - Pharmacokinetic and pharmacodynamic comparison of immediate-release and sustained release adinazolam mesylate tablets after single- and multiple-dose administration. AB - The effect of adinazolam release rate on psychomotor performance and sedation was assessed by administering 40 mg adinazolam mesylate immediate-release (CT) tablets, 60 mg sustained-release (SR) tablets, and placebo in a double-blind crossover study in 15 healthy male subjects. A separate panel of 16 subjects received the above single doses and multiple-dose regimens of 40 mg CT tablets every 8 hr and 60 mg SR tablets every 12 hr according to a crossover design. Psychomotor performance was assessed by digit symbol substitution test, card sorting tasks, and sedation ratings. Following single-dose administration, dose corrected adinazolam and N-desmethyladinazolam (NDMAD) AUC values were equivalent for SR and CT tablets. Peak adinazolam and NDMAD levels were lower and occurred later for the SR tablets. Decrements in card sorting were 50 and 3% at 1 hr and 17 and 20% at 6 hr for the CT and SR tablets, respectively. Maximal sedation scores were lower for the SR tablets compared to the CT. Dose-corrected AUC was comparable between single and multiple doses for both adinazolam and NDMAD; no differences were observed in 24-hr AUC at steady-state between CT and SR tablets. Fluctuation ratios were reduced for both adinazolam and NDMAD following SR tablets. Psychomotor and sedative effects were attenuated upon multiple dosing. Thus, the reduction in peak plasma NDMAD following SR tablet administration results in a lesser sedation and psychomotor impairment on acute administration, and tolerance to these effects occurs on multiple dosing. PMID- 1495890 TI - The pharmacokinetics of trilostane and ketotrilostane in an interconverting system in the rat. AB - The pharmacokinetics of trilostane and one of its metabolites ketotrilostane are described and characterized in the rat following the separate intravenous administration of trilostane and ketotrilostane. It was noted during these studies that the parent compound and its metabolite undergo metabolic interconversion-trilostane producing ketotrilostane and ketotrilostane generating trilostane. This result means that trilostane is conserved in the body by interconversion--being metabolized to ketotrilostane and then subsequently back to the "parent" drug, trilostane. PMID- 1495891 TI - Saturable tissue binding and imirestat pharmacokinetics in rats. AB - To investigate the hypothesis that the pharmacokinetics of imirestat, an aldose reductase inhibitor, are influenced by saturable binding to tissues, three experiments were done. (1) The nature of the dose dependence was characterized in rats. Two groups of nine adult male Sprague-Dawley rats received iv 14C-imirestat at doses of 2 or 8 mg/kg. Serial blood samples were obtained over 15 days. Volume of distribution at steady-state was significantly different between the high- and the low-dose groups (0.744 +/- 0.103 l and 1.10 +/- 0.228 L, respectively). Clearance was independent of dose over this fourfold range (approximately 15 ml/hr). (2) The effect of either statil or AL3152, both aldose reductase inhibitors and potential competitors for aldose reductase binding, on the pharmacokinetics of a single 0.2-mg/kg iv dose of imirestat was assessed. A 2.4 mg/kg loading dose of statil was administered and a constant-rate infusion (56 micrograms/hr/kg) was begun 16 hr before imirestat. A 2-mg/kg loading dose of AL3152 and a constant-rate infusion (115 micrograms/kg/hr) were also administered 16 hr before imirestat. The infusions were maintained throughout the study. AL3152 administration decreased the imirestat steady-state volume of distribution by a mean of 63%. Statil administration decreased it by a mean of 39%. (3) The dosing regimen of the second study was repeated and, at two sampling times, nine tissues and plasma were obtained from four rats per sampling time for determination of imirestat tissue-to-plasma concentration ratio. The tissue/plasma imirestat concentration ratio in the adrenals 24 hr after imirestat administration was 56.9 +/- 20.0 in the imirestat group, 17.7 +/- 1.27 in the statil-coadministered group, and 12.3 +/- 2.59 in the AL3152-coadministered group.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1495892 TI - The in situ acetylation of an immobilized human serum albumin chiral stationary phase for high-performance liquid chromatography in the examination of drug protein binding phenomena. AB - The in situ modification of an immobilized human serum albumin (HSA) high performance liquid chromatographic chiral stationary phase by p-nitrophenyl acetate is reported. This procedure, which is thought to affect primarily a single reactive tyrosine residue within the protein structure, influenced the chromatographic retention and enantioselectivity factors of a wide range of solutes. For certain solutes, increases in both capacity factor and chiral resolution were observed. Ultrafiltration studies on representative test solutes using free HSA, treated in a similar manner to the immobilized protein, gave similar results as the chromatographic observations, indicating that the latter effects are not artifactual results of immobilization. The effect of the modification of HSA on the binding behavior of drugs reportedly sharing the site predominantly affected by the derivatization, namely, the indole-benzodiazepine binding site, varied greatly. This observation suggests that the affected binding area is not a single, tightly structurally defined site. PMID- 1495893 TI - An air-gap enzyme electrode: development and applications. AB - A novel air-gap enzyme electrode was developed by amalgamating the principles controlling ion-selective electrodes, enzyme kinetics, and diffusion of molecules across membranes. Commercially available ammonia and carbon dioxide gas-sensing electrodes were modified to measure the respective gases over a head-space. A plexiglass cell was designed and fabricated to house the modified electrodes. The air-gap electrodes exhibited superior sensitivity and response characteristics compared to the original membrane electrodes. The plexiglass cell was divided into two compartments by virtue of a selectively permeable membrane. Enzymatic reactions were conducted in the cell to determine quantitatively the concentration of the substrate. L-Phenylalanine ammonia lyase was used to determine L-phenylalanine with the ammonia electrode and L-glutamate decarboxylase was utilized for the determination of L-glutamic acid by the carbon dioxide electrode. Near-Nernstian slopes were obtained for the response of the enzyme electrodes. In addition to the good reproducibility, the method provided unique ability to reuse the same enzyme solution for several determinations of various concentrations of the analyte. The performance of the two compartment cell and air-gap enzyme electrode was found to be superior in comparison to conventional enzyme electrodes. PMID- 1495894 TI - Stereoselective enzymatic hydrolysis of various ester prodrugs of ibuprofen and flurbiprofen in human plasma. AB - The hydrolysis kinetics of various alkyl, glycolamide, aminoethyl, and 2-(1 imidazolyl)ethyl esters of ibuprofen and flurbiprofen in 80% human plasma were investigated using a direct high-performance liquid chromatographic assay for the enantiomers of these acids. In each case, the R-isomer ester was found to undergo faster plasma-catalyzed hydrolysis than the corresponding S-isomer. The difference in the hydrolysis rates between the enantiomeric forms ranged from a factor of 1.4 for the N,N-diethylglycolamide ester of ibuprofen to a factor of 50 and 25 for the 2-(1-imidazolyl)ethyl ester of ibuprofen and flurbiprofen, respectively. Therefore, enantioselective differences in plasma-catalyzed ester prodrug hydrolysis must be taken into account when evaluating prodrugs of racemic mixtures of chiral drugs. PMID- 1495895 TI - The in vitro enzymic labilities of chemically distinct phosphomonoester prodrugs. AB - The kinetics of decomposition of phosphomonoesters of hydroxymethyl-5,5 diphenylhydantoin (1), estrone (2), 17 beta-testosterone (3), 1-phenylvinyl alcohol (4), and 17 alpha-testosterone (5) were studied in rat whole blood at 25 and/or 37 degrees C. As the acidity of the leaving hydroxyl group of the phosphomonoester increased, there was a tendency for the rate of hydrolysis to increase, except for the anomalous behavior of 4, which was consistent with its relative rate of hydrolysis in aqueous solutions (1). In addition, the kinetics of hydrolysis of 1-5 and p-nitrophenyl phosphate (p-NPP) were studied in the presence of isolated alkaline phosphatases from a variety of sources. The initial rate of production of 17 alpha- and 17 beta-testosterone from their respective phosphate esters (5 and 3), in the presence of human placental alkaline phosphatase, revealed that 3 was hydrolyzed 5.3-fold more rapidly than 5. This difference in reactivity might have been the result of differences in the stereochemical and/or steric nature of the two isomers. For p-NPP, 1, 2, and 4, the kcat and kcat/Km values determined in the presence of the various alkaline phosphatases showed little variation, whereas for 3, the catalytic constants, kcat and kcat/Km, were found to be dramatically less than those found for p-NPP, 1, 2, and 4.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1495896 TI - Amino acid side-chain contributions to free energy of transfer of tripeptides from water to octanol. AB - The location of amino acids in soluble or membrane proteins is related to the hydrophobicity of the side chains. Amino acid hydrophobicity values are based upon the thermodynamics of transfer from an aqueous to a nonaqueous environment. However, for certain hydrophilic residues uncertainty exists on the appropriate hydrophobicity values. We have measured the octanol-water partition coefficients (Po/w) of tripeptides of the sequence N-14C-acetyl-Ala-X-Ala-NH-tButyl (AcAlaXAlaNHtButyl), where the central residue X was either Gly, Ala, Phe, Trp, Pro, His, Asp, or Glu. The Po/w for the tripeptides agreed reasonably well with values calculated by the fragment method of D. J. Abraham and A. J. Leo (Proteins Struct. Func. Gen. 2, 130-152, 1987). The log Po/w of the uncharged form was 1.6, 2.7, and 2.5 greater than the log Po/w of the ionized form for the His, Asp, and Glu peptide, respectively. The new data on the pH dependence of the ionizable side chains, His, Asp, and Glu, should result in better prediction of the partition coefficient of peptides as a function of pH. The thermodynamic parameters were determined from the temperature dependence of partitioning. In the temperature range studied (2 to 65 degrees C) the transfer of tripeptides from water to octanol was entropy governed except for the ionized peptides. A heat capacity term was necessary to account for the transfer of tripeptides containing non polar residues. The heat capacity change for transfer from water into octanol was -45, -73, -81, and -88 cal/mol K for Ala, Phe, Trp, and Pro peptides, respectively. Peptides containing Gly, His (pH 7.2), and the uncharged forms of Asp, Glu, and His did not show a significant change in heat capacity. The side-chain contribution of the central residue X (delta Gx) to the free energy of transfer was obtained from the difference between the free energy of transfer of the peptide containing the central residue X and the Gly peptide; delta Gx = delta G(AcAlaXAlaNHtButyl) - delta G(AcAlaGlyAlaNHtButyl). The relative order of hydrophobicity of the side chains correlated well with previous studies. However, a significant difference was found for the absolute hydrophobicity between the present study and experimental data on N-acetyl amino acid amide derivatives (J. Fauchere and V. Pliska, Eur. J. Med. Chem. 18(4), 369 375, 1983).(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1495897 TI - Nebulization of liposomes. III. The effects of operating conditions and local environment. AB - Multilamellar liposomes (MLV) of saturated phosphatidylcholine and dipalmitoyl phosphatidylglycerol (DPPG) (9:1 mole ratio) containing 5,6-carboxyfluorescein (CF) were prepared and extruded through 1.0-micron polycarbonate membranes. Diluted aqueous dispersions were aerosolized for a total of 80 min using a Collison nebulizer under a variety of conditions. The effects of air pressure, temperature, buffer osmotic strength, and pH on nebulized liposome dispersions were studied. Changes in air pressure produced large changes in the percentage release of CF and ranged from 1.3% (4 psig) to 88.2% (50 psig) after 80 min of nebulization. The temperature of the nebulizer dispersions dropped during experiments. The extent of the temperature drop varied according to the air pressure used and ranged from 5 degrees C (4 psig) to 11 degrees C (greater than or equal to 30 psig). The temperature of dispersions caused no increase in CF release until the gel-to-liquid crystalline transition temperature was exceeded (54.6 degrees C), whereupon a 20% increase in leakage was observed after 80 min of nebulization. Aerosol mass output was relatively unaffected by the starting temperature of experiments when conducted within the ambient temperature range. Leakage from the liposomes was increased in hypotonic solution but decreased in hypertonic solutions. At a buffer pH of 2.85 the percentage leakage of CF was increased approximately 18% compared to that at pH 7.2 and pH 10.75. Results show that the stability of liposomes composed of saturated phosphatidylcholine and DPPG (9:1 mole ratio) is affected by the operating and environmental conditions under which aerosolization takes place, with air pressure having the greatest effect. PMID- 1495898 TI - Infrared imaging of pharmaceutical materials undergoing compaction. AB - The goal of this study was to use infrared thermography as a new technique to investigate the heat released during compaction and consolidation of pharmaceutical powders and granules. Real-time temperature measurements without physical contact with tablets were provided by a highly sensitive (+/- 0.1 degrees C at 30 degrees C) infrared camera (Agema Infrared Systems, Model 470 with CM-SOFT software). High-resolution images were captured at the takeoff point, i.e., less than 1 sec after compaction, stored on floppy disks, and then analyzed on a regular PC equipped with a VGA color monitor. Thermal surface profiles of tablets were obtained with high geometric and temperature resolution. Reproducibility of the camera readouts was better than 3%. The model granulation used was a direct compression blend of microcrystalline cellulose, spray-dried lactose, and magnesium stearate. This blend was compressed using an instrumented Korsch PH106 rotary press fitted with 1 station of 19.1 x 7.9-mm (0.750 x 0.312 in.) capsule-shaped tools. The effects of compaction force (6-20 kN), rate (130- to 360-msec contact time), and lubricant level (0.5 and 1.0%) on postcompaction temperature rise, caused by heat released during compaction, were investigated. The presence and location of nonhomogeneous heat distribution were assessed as well. Results have shown that the heat released during compaction increases with compaction force. Tablet surface temperatures of 33.8 +/- 0.7 degrees C were observed at 20 kN compaction force in contrast to 29.5 +/- 0.3 degrees C at 6.7 kN.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1495900 TI - Phagocytosis of nanoparticles by human immunodeficiency virus (HIV)-infected macrophages: a possibility for antiviral drug targeting. AB - Human monocytes/macrophages (MO/MAC) were isolated from peripheral blood and cultivated on hydrophobic Teflon membranes. This culture system is suitable for HIV infection of MO/MAC in vitro. After transfer into 24-well plates the mature macrophages (infected or uninfected) were used for measurements of phagocytosis. The uptake of different, radioactively labeled nanoparticles (NP) made of polyalkylcyanoacrylate, polymethylmethacrylate (PMMA), and human serum albumin (HSA) by the macrophages was determined. In addition, the influence on phagocytosis of size and composition, concentration, and surface of the NP was studied. Further, macrophages of different state of activation were tested. NP made of polyhexylcyanoacrylate (PHCA) or human serum albumin with a diameter of about 200 nm were found most useful for targeting antiviral substances such as azidotymidine to macrophages. Cells infected in vitro with HIV-1D117/III, a monocytotropic HIV isolate from a perinatally infected child, possessed an even higher phagocytotic activity than noninfected cells. Macrophages isolated from HIV-infected patients also showed good incorporation of NP. Thus, the concept of a specific targeting of antiviral substances to macrophages in HIV-infected individuals appears quite promising. PMID- 1495899 TI - Aminopeptidase activity in the jejunal and ileal Peyer's patches of the albino rabbit. AB - The objectives of this study were (a) to compare the aminopeptidase activity in the Peyer's patches of the jejunum and ileum of the albino rabbit against that in the adjacent patch-free segments and (b) to determine the relative sensitivities of the aminopeptidase activity in the Peyer's and non-Peyer's patches to aminopeptidase inhibitors and penetration enhancers. The results indicated that the Peyer's patches were about equal in aminopeptidase activity in the jejunum and in the ileum but were only 20-30% as rich in aminopeptidase activity as their neighboring patch-free areas. Compared to non-Peyer's patches, the aminopeptidase activity in the Peyer's patches was not as sensitive to the inhibitory effect of amastatin. It was, however, much more sensitive to the inhibitory effect of puromycin and p-chloromercuribenzoate and was somewhat more sensitive to the inhibitory effect of Na deoxycholate, Na glycocholate, and polyoxyethylene-9 lauryl ether. Therefore, based on substrate preferences and on the relative sensitivity of aminopeptidase activity to inhibition by aminopeptidase inhibitors and penetration enhancers, the relative proportions of various aminopeptidases in the Peyer's patches and in the non-Peyer's patches are likely different. PMID- 1495901 TI - Bioadhesion by means of specific binding of tomato lectin. AB - The possibility of developing bioadhesive drug delivery systems on the basis of molecules which selectively bind to the small intestinal epithelium by specific, receptor-mediated mechanisms was investigated using a lectin isolated from tomato fruits (Lycopersicum esculentum). The tomato lectin (TL) was found to bind specifically onto both isolated, fixed pig enterocytes and monolayers of human Caco-2 cell cultures with a similar affinity. TL-coated polystyrene microspheres (0.98 micron) also showed specific binding to enterocytes in vitro. Lectin binding was found to be favored at neutral pH and to be reduced in an acidic environment. Crude pig gastric mucin, however showed a marked cross-reactivity in vitro, indicating that lectin binding to the cell surface in vivo might be inhibited by mucus. PMID- 1495902 TI - Influence of supersaturation on the pharmacodynamic effect of bupranolol after dermal administration using microemulsions as vehicle. AB - Transdermal absorption of drugs is limited by the stratum corneum, which serves as a diffusion barrier. This barrier might be overcome by enhancing the thermodynamic activity of the drug vehicle. Thermodynamic activity is particularly high in supersaturated systems because it is directly correlated with the degree of saturation. Since supersaturated systems are not stable, they were formed in situ by application of water-free microemulsion bases. These water free microemulsion bases saturated with the drug were applied to New Zealand albino rabbits with an occlusive patch. Occlusion leads to water uptake from the skin due to hydratation and changes the microemulsion base into a microemulsion. The microemulsion will become supersaturated as a result of decreasing solubility of the drug with increasing water content. The pharmacodynamic effect of the model drug bupranolol in vivo was investigated over a 10-hr time period. The in vitro solubility of bupranolol was examined with respect to the water content. The solubility vs water content curves were compared to the effect vs time curves. The microemulsions and their individual components were studied, and the effect vs time curves were inversely correlated with the solubility vs water content curves. PMID- 1495904 TI - Physicochemical properties of the novel heteropolyanion antiviral hexapotassium alpha-vanado-11-tungstoborate (DuP 925). AB - Hexapotassium-alpha-vanado-11-tungstoborate (DuP 925) is a yellow irregular shaped crystalline powder. The DSC thermogram indicates that decomposition begins to occur above 250 degrees C. The compound exhibits a volatile loss of 3.7% by thermogravimetric analysis. The drug substance adsorbs water reaching a 7.1% volatile loss after 3 weeks at 85% relative humidity. The solubility of DuP 925 in water is high (1.6 g/ml at pH 4.8). Changes in pH have a negligible effect on the solubility with values of 1.3 g/ml in 0.1 N HCl and 1.4 g/ml in 0.1 N NaOH. The solubility is minimally affected by changes in sodium ion concentration. The compound ion pairs with tetrabutyl-ammonium ions at 1:2 and 1:6 ratios, with the 1:6 ion pair having an affinity over six orders of magnitude greater than that of the 1:2 ion pair. The degradation of DuP 925 in solution follows apparent first order kinetics over the pH range of 0.6 to 12.6 at 80 degrees C. Citrate, EDTA, and phosphate buffers are catalytic at the pH minimum, with citrate and EDTA being stronger catalysts than phosphate. Acetate buffers appear to have negligible catalytic effects at pH 4 to 5. The degradation proceeds through the formation of the symmetrical dodecatungstoborate [BW12O40]-5. In acid, the dodecatungstoborate is stable, while in base it degrades further. Increasing the ionic strength has a catalytic effect on the degradation of DuP 925, while changes in the initial concentration of DuP 925 have a negligible effect on the stability. The pH-rate profile indicates a pH minimum of approximately 3. PMID- 1495903 TI - Sonophoresis. I. The use of high-frequency ultrasound to enhance transdermal drug delivery. AB - Previous attempts to use ultrasound (less than or equal to 1-MHz frequency and 1 to 3-W/cm2 intensity) to enhance transdermal drug delivery (so-called sonophoresis) have produced inconsistent results. Theoretical analysis of ultrasound propagation in tissue predicts that higher-frequency ultrasound (greater than 1 MHz) will increase the concentration of energy deposition in the stratum corneum (SC) (typically, the rate-limiting barrier to percutaneous penetration). This hypothesis was tested by comparing the passive transdermal delivery of salicylic acid with that under the influence of ultrasound at 2-, 10 , and 16-MHz frequency; measurements were performed in vivo in hairless guinea pigs. Total drug absorbed was quantified by determining the amount of salicylic acid (1) present in SC tape strips and (2) eliminated in urine. Sonophoresis for 20 min at 2 MHz caused no significant increase in salicylic acid delivery over passive diffusion; treatment with ultrasound at 10 and 16 MHz, on the other hand, significantly elevated salicylic acid transport, by 4-fold and 2.5-fold, respectively. Kinetic analysis of the sonophoretic data at 10 and 16 MHz also revealed that the diffusion lag time associated with transdermal drug delivery (TDD) was reduced. A shorter period (5 min) of sonophoresis again resulted in enhanced TDD (relative to the corresponding control) at the higher frequencies; the delivered dose, and the level of enhancement, however, were lower than those after the 20-min treatment.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1495905 TI - 1H-nuclear magnetic resonance (NMR) studies on the inclusion complex of prostaglandin E1 (PGE1) with alpha-cyclodextrin. AB - Prostaglandin E1 is currently marketed as a freeze-dried injectable inclusion complex with alpha-cyclodextrin for the treatment of peripheral arterial diseases. alpha-Cyclodextrin is used as a stabilizing agent and to improve the dissolution characteristics of prostaglandin E1. Upon dilution with the infusion medium, the inclusion complex dissociates almost completely as shown by NMR chemical shift measurements of the complexed and uncomplexed prostaglandin E1. Nuclear Overhauser effect (NOE) measurements of the interacting atoms of alpha cyclodextrin and prostaglandin E1 provide insight into the structure of the complex. PMID- 1495906 TI - A flexible automated dissolution testing system for use with either USP apparatus 1 or USP apparatus 2. PMID- 1495907 TI - Determination of dissociation constants of selected cyclodextrin-benzaldehyde inclusion complexes using pulse polarography. PMID- 1495908 TI - [The significance of the surfactant system for preventing infection]. PMID- 1495909 TI - [Pulmonary function tests after pneumocystis carinii pneumonia in HIV infected patients]. AB - Significant impairment of lung volumes and gas exchange in HIV-infected patients with acute Pneumocystis carinii pneumonia (PCP) has been reported, whereas little is known about lung function compromise following successful therapy. In 9 patients with acute PCP and 9 patients 1-5 month after PCP lung function testing including spirometry, diffusing capacity for carbon monoxide and exercise blood gas analysis were performed serially at monthly intervals. The results were summarized in a total score. The mean period of follow-up for each patient was 7.2 +/- 2 months. A decrease in lung volumes (FEV1 67 +/- 14.2% pred.norm., VC 72.7 +/- 11.9% pred.norm.) and gas exchange (CO-transfer factor 53.2 +/- 18.5% pred.norm., CO-transfer coefficient 67.8 +/- 14.2 pred. norm.) was observed in all 9 patients with acute PCP. Post-PCP lung volumes normalized within 1 month, whereas disorders in gas exchange persisted for 1-3 months. The total score normalized in 16/18 patients. One of the remaining patients with persisting functional impairment had chronic obstructive airway disease, whereas in the other dysfunction was even observed prior to PCP and no diagnosis could be obtained. 2-6 months following acute disease a second period of decreased lung function occurred in 6 pts. In 3 of the 6 there were no clinical signs of infection (rebronchoscopy refused), in 1 patient infection with cytomegalovirus was suspected. In the other 2 patients a relapse of PCP was diagnosed by bronchoscopy. CONCLUSIONS: Acute PCP compromises lung mechanics and gas exchange. During recovery deficits in gas exchange persist longer than diminished lung volumes.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1495910 TI - [Results of CT-controlled puncture of the thorax]. AB - Results of 56 CT-guided biopsies in 45 patients are presented. Aspiration biopsies (n = 23) had a usable result in 75% of the cases; cutting biopsies (n = 33) in 80%. The main complication was the pneumothorax with 9%; in one patient the procedure caused a haemoptoe. PMID- 1495911 TI - [The "sarcoidosis-lymphoma syndrome"--a lymphocyte dysregulation?]. AB - Sarcoidosis and malignant lymphoma can occur in the same patient; sarcoidosis appears first, the malignant lymphoma follows later. The case histories of three patients illustrate what Brinker first coined as the "sarcoidosis-lymphoma syndrome". In two patients a pulmonary sarcoidosis stage I was diagnosed over 30 years respectively 4 years prior to the histological diagnosis of highly malignant Non-Hodgkin lymphoma. The third patient suffered from generalized sarcoidosis with splenomegaly, , granulomatous hepatitis and interstitial lung disease, in addition to which a lymphoproliferative syndrome was diagnosed. Comparing the pathogenesis of malignant lymphoma and sarcoidosis, parallels such as T-cell dysfunction, which probably facilitates malignant transformation of B cells, become apparent. In both diseases the transforming gene could be the Ebstein-Barr virus. PMID- 1495912 TI - [Thoracic endometriosis--2 case reports and review of the literature]. AB - Thoracic endometriosis is characterised by recurring pulmonary symptoms in association with the menstrual period. Pleural endometriosis manifests itself as recurring pneumothorax or hematothorax while pulmonary endometriosis is characterized by hemoptysis. The pathogenetic mechanism is not completely understood but it appears that hematogenous and lymphangitic embolization of endometrial tissue may play a significant part in parenchymal and pleural endometriosis respectively. Clinical symptoms begin with ovulation. Hemoptysis is explained by sloughing off of decidual tissue and an increased capillary fragility during menstruation. Rupture of pleurally based alveoli in the vicinity of endometrial tissue or necrosis of the diaphragm at the side of diaphragmatic endometrial implants might be causative for the development of a pneumothorax. Therapy of both forms of thoracic endometriosis consists in hormonal suppression but in some cases surgical intervention might become necessary. PMID- 1495913 TI - [Invasive aspergillosis in cavitary lung sarcoidosis]. AB - Pulmonary sarcoidosis is a granulomatous disorder of unknown origin with a favorable outcome in most patients. However in about 5-10% progressive fibrosis is observed and may lead to further complications. We report on a 49 year-old woman with sarcoidosis with fibrotic changes and cavities in both upper lobes, who developed an upper lobe infiltration resistant to antibiotic treatment. Histologic examination of bronchial biopsy specimen revealed invasive aspergillosis. Therapy with Amphotericin B and Flucytosin was followed by marked clinical and radiological improvement. PMID- 1495914 TI - Ultrastructure of the developing protonephridial system of the cercaria of Philophthalmus sp. (Trematoda, Digenea). AB - The fully developed flame bulb of Philopthalmus exhibits the structure characteristic of Trematoda and Monogenea: external and internal ribs forming a weir, external and internal leptotriches, and two longitudinal cytoplasmic cords connected by a septate junction. The proximal canal has a septate junction and surface lamellae. In developing cercariae, perikarya of terminal and proximal canal cells are close together, and sheet-like outgrowths of the terminal cell are externally surrounded by cytoplasm of the proximal canal cell containing a septate junction. Internal outgrowths and external cytoplasm are connected by many "membranes", i.e. desmosome-like structures. Internal sheets break up into internal ribs, and the external cytoplasm breaks up into external ribs, external and internal ribs connected by the filtration "membrane". The developing distal excretory duct possesses a septate junction and many branching and looping lamellae. A comparison of Philopthalmus with the cestode Austramphilina elongata, the only other platyhelminth species in which the development of the protonephridia has been studied at the ultra-structural level, revealed that the two species differ in the presence and absence, respectively, of a septate junction in the flame bulb at an early stage of development. PMID- 1495915 TI - Comparative investigations of the morphology and chemical composition of the eggshells of Acanthocephala. III. Eoacanthocephala. AB - Eggshells of the eoacanthocephalans Neoechinorhynchus rutili (Neoechinorhynchidae) and Paratenuisentis ambiguus (Tenuisentidae) were investigated for their fine structure and their chemical composition. The acanthor larvae of P. ambiguus are surrounded by four eggshells (E1-E4) separated by electron-lucent interstices (G1-G4). This resembles the stratification of the eggshells of archiacanthocephalans and palaeacanthocephalans. However, an additional outer envelope (E0) exists in N. rutili. In mature eggs of this species, the broad interstice between E0 and E1 is densely packed with polysaccharides, but the other interstices also showed an intense Thiery label. In both species, E2 along with its outer protuberances contains keratin, as does E2 in archiacanthocephalans and palaecanthocephalans, whereas E4 does not contain chitin, which contrasts with findings in the eggs of the two other classes of acanthocephalans. The results are discussed with respect to the classification of the Acanthocephala and to their transmission to the intermediate hosts. PMID- 1495916 TI - Worm burden and leukocyte response in Angiostrongylus malaysiensis-infected rats: the influence of testosterone. AB - Gonadectomized male albino rats aged 7 weeks were given 1.5 mg/kg testosterone propionate daily and inoculated with 50 third-stage larvae of Angiostrongylus malaysiensis. The treatment significantly increased the number of larvae and adult worms recovered from the brain and pulmonary arteries, respectively, and the rats exhibited smaller thymus glands. The total numbers of leukocytes, monocytes, neutrophils, and especially eosinophils increased significantly post infection, but the counts were higher in the untreated infected controls. Presumably, immunosuppressive effects of testosterone may at least partly be responsible for the higher loads of A. malaysiensis worms found in male rats as compared with females in the field. PMID- 1495917 TI - Light and scanning electron microscopy studies on the effects of the enantiomers of praziquantel and its main metabolite on Schistosoma mansoni in vitro. AB - In the present study, the effects of the enantiomers of the anthelmintic drug praziquantel (PZQ) and its main metabolite trans-4-hydroxy-praziquantel (TRANS) on pairs of Schistosoma mansoni worms were examined in vitro. Highly purified enantiomers (optical purity, greater than 99.9% for PZQ and 99.0% for TRANS) were used. Paired worms were incubated for 4 h in RPMI medium containing 0.01, 0.02, 0.075, 0.1, 2.5, 10, and 100 micrograms PZQ or TRANS enantiomers/ml, respectively, before being transferred to drug-free medium for another 20 h. PZQ is used as a racemate in the therapy, and its effect is attributed to the R(-) enantiomer. R(-)-PZQ and R(-)-TRANS proved to be at least 10(5) times more effective than the respective S(+)enantiomers, causing tegumental damage and surface blebbing on S. mansoni. As judged from the effective doses in 50% of the worms (ED50 values); R(-)-PZQ and R(-)-TRANS showed nearly the same efficacy against adult S. mansoni. Male worms reacted more sensitively than did females. As determined by scanning electron microscopy, alterations in lethally damaged worms depended on the drug used, even following incubation at the lowest concentration tested (0.01 microgram/ml). Worms exposed to R(-)-TRANS were elongated, whereas treatment with R(-)-PZQ led to contractions and twisted parasites. Both compounds caused excessive surface blebbing along the dorsal side of the worms' tegument. PMID- 1495918 TI - Ultrastructural detection in vitro of WGA-, RCA I-, and Con A-binding sites involved in the invasion of heart muscle cells by Trypanosoma cruzi. AB - The presence of carbohydrate residues in the plasma membrane of normal and Trypanosoma cruzi-infected heart muscle cells was investigated cytochemically using ruthenium red, lanthanum nitrate, periodic acid Schiff/thiocarbohydrazide/silver, and gold- and ferritin-lectin complexes. The study combined conventional electron microscopy with the new analytical technique of electron spectroscopic imaging (ESI). Galactosyl, mannosyl, and sialyl residues were detected in regions of host-cell plasma membrane that undergo interiorization together with the parasite. Lectin-binding sites were sometimes found to show a punctate or patchy distribution in the endocytic vacuole membrane. These findings suggest the that glycoconjugates cytochemically detected in the host-cell plasma membrane participate in the invasion of heart muscle cells by T. cruzi. PMID- 1495919 TI - Anaplasma marginale: failure of sera from immune cattle to confer protection in passive-transfer experiments. AB - High levels of immunity to Anaplasma marginale were induced in cattle either by vaccination using sonically disrupted A. marginale-infected erythrocytes or by repeated infection with different strains of the rickettsia. In both instances, high levels of anti-A. marginale antibody were detected in the sera of the immune cattle by immunoblotting. Serum from one animal that had been made immune by repeated infection was transferred intravenously to A. marginale-susceptible calves (three non-splenectomised and two splenectomised) undergoing initial A. marginale infection at serum doses of 2-10 ml/kg. Neither the course nor the outcome of infection as indicated by the parasite levels attained or the level of anaemia induced was altered in the calves that received the immune serum relative to the course or outcome of infection in control calves (two non-splenectomised and two splenectomised) that received serum from an two splenectomised) that received serum from an A. marginale-naive donor animal. In a similar experiment, a pool of sera from four steers that had been vaccinated with sonically disrupted A. marginale initial bodies was transfused into two intact A. marginale susceptible calves during the early stage of A. marginale infection at a dose of 10 ml/kg. No difference was observed in the course or outcome of infection in these calves relative to the course or outcome of infection in the two non splenectomised calves that were transfused with non-immune serum.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1495921 TI - Growth of Babesia bigemina parasites in suspension cultures for vaccine production. AB - An Australian Babesia bigemina vaccine strain was maintained in suspension culture for 40 days. Parasite growth was compared using two tissue-culture flask sizes (25 and 75 cm2), four gas mixes (2%, 2.5%, 3% and 3.5% O2; 5% CO2; and the balance N2) and four packed blood cell (PCV) volumes (7%, 9%, 13% and 18%). The best continuous parasite yields were obtained from suspension cultures in 75-cm2 flasks at a PCV of 13% and gas mixtures of 2%-3% O2, 5% CO2 and the balance N2. Parasite yields per millilitre of culture medium were 3 times those obtained in microaerophilous stationary-phase cultures. The method has thus far been used for 6 months to produce the Australian requirements for live B. bigemina vaccine. PMID- 1495920 TI - Labeling and initial characterization of polar lipids in cultures of Plasmodium falciparum. AB - The present report describes the radioactive labeling of polar lipids in in vitro cultures of Plasmodium falciparum as well as their extraction with organic solvents and their partial characterization by chemical and enzymatic methods. All substances detected could be cleaved by alkali, suggesting that they were esters rather than sphingolipids or compounds containing alkyl groups. Dolichol cycle intermediates were not detected. Phosphatidylinositol, phosphatidylethanolamine, and phosphatidylcholine were labeled by fatty acids and inositol or ethanolamine, respectively, confirming their de novo synthesis by the parasite. Metabolic labeling with glucosamine and cleavage by phosphatidylinositol-specific phospholipase C provided evidence of the formation of N-acetyl-glucosaminyl-phosphatidylinositol, an obligate precursor in the biosynthesis of glycosylphosphatidylinositol membrane anchors of proteins. PMID- 1495922 TI - Immunoprotection in mice susceptible to waning memory against the pre erythrocytic stages of malaria after validated immunisation with irradiated sporozoites of Plasmodium berghei. AB - The induction of immunity by irradiated sporozoites has been a bench-mark of immunological protection against the malaria parasite. Herein we confirm that different mouse strains exhibit different susceptibilities to sporozoite-induced infection of Plasmodium berghei. We note, however, that after hepatic schizogony, early parasite growth in the blood demonstrates no strain preference between C57BL/6 and BALB/c mice. Sporozoite-susceptible C57BL/6 mice, although initially protected by irradiated sporozoite immunisation against a challenge of 10(3) live sporozoites, progressively lose this protection; a challenge with fewer sporozoites 2 months later elicits a blood infection. BALB/c mice treated in parallel remain protected. Analysis of the kinetics of blood parasitaemia (a measure of hepatic schizont burden) with waning protection shows clearly that immunocompetence remains, as indicated by a reduction in the effective exo erythrocytic schizont load. This immunocompetence can be shown to be absolutely protective, given an appropriately low dose of viable infective sporozoites. We discuss the testable proposition that this elicitation of protective memory is a consequence either of 'unsaturated' threshold levels of recirculating immunoeffector CD8+ cells or of CD4 cell activation by nonviable sporozoites. PMID- 1495923 TI - Analysis of pathogenicity by restriction-endonuclease digestion of amplified genomic DNA of Entamoeba histolytica isolated in Pernambuco, Brazil. AB - The pathogenicity of 47 strains of Entamoeba histolytica isolated in Pernambuco, Brazil, was examined using the polymerase chain reaction (PCR) followed by restriction-endonuclease digestion. Electrophoretic patterns of PCR products digested with HinfI revealed that all strains were nonpathogenic. The results were entirely in accord with phenotypic properties such as isoenzyme patterns and the failure to bind a pathogenic-isolate-specific monoclonal antibody. When the sensitivity of PCR was examined, amplified products could be detected from template DNA equivalent to five trophozoites. These observations indicate that PCR amplification of genomic DNA and subsequent restriction-enzyme digestion is a useful strategy for obtaining a sensitive and accurate diagnosis. The present study also demonstrates that nonpathogenic strains of E. histolytica predominate in northeastern Brazil. PMID- 1495924 TI - High osmotic pressure enables fine ultrastructural and cytochemical studies on Pneumocystis carinii. I. Epon embedding. AB - High osmotic pressure was used to preserve the ultrastructure of rabbit-, SCID mouse-, and rat-derived Pneumocystis carinii organisms from osmotic stress during fixation. Organelles and cytosol were well preserved within the tonicity range of 850-1,300 mosmol. Under these experimental conditions, we determined that the endoplasmic reticulum was well developed in all parasite stages and could observe the Golgi complex, autophagic vacuoles, dense bodies, type II endoplasmic saccules, and the recently described outer surface membrane, which was found in all parasite stages. The biological implications of these findings are discussed. PMID- 1495925 TI - Early enhanced growth of the digestive gland of Biomphalaria glabrata infected with Schistosoma mansoni: side effect or parasite manipulation? AB - We carried out a comparative study of the dynamics of the sporocyst population and the growth rate of the host habitat (digestive and genital gland) within the Schistosoma mansoni/Biomphalaria glabrata system during monomiracidial infections. The volume of the digestive gland increased sharply during the first 2 weeks of infection and then decreased at 2-4 weeks post-infection during the exponential growth phase of the sporocyst infrapopulation. The effects of the parasite on the development of the host's genital gland resulted in a slowing of the growth of the ovotestis. These interactions, related to the demographic processes involved in the intramolluscal development of the parasite population, were interpreted in relation to the spatial and energy constraints imposed by the developmental needs of both the parasite and the host. PMID- 1495926 TI - Long-term conservation of Muellerius capillaris (Nematoda, Protostrongylidae) first-stage larvae: cryopreservation versus storage at -20 degrees C. PMID- 1495927 TI - A survey of Blastocystis in reptiles. AB - A total of 28 species of reptiles were investigated for Blastocystis using light microscopy and in vitro culture in biphasic egg slant medium. Blastocystis species were detected in 8 (28.6%) of these 28 species in 3 tortoises (Geochelone elephantopus, G. elegans and G. carbonaria), 3 snakes (Boiga dendrophilla, Python reticulatus and Elaphe radiata), 1 crocodile (Crocodylus porosus) and 1 iguana lizard (Cyclura cornuta). The reptilian Blastocystis appeared to be morphologically similar to B. hominis. PMID- 1495928 TI - The correlation of Ki67 growth factor and ERICA in breast cancer. AB - Estrogen receptor (ER) status is an accepted prognostic indicator for breast cancer when measured by either the biochemical or immunohistochemical (ERICA) methods. Moreover, ERICA was found to be a better predictor of survival in human breast cancer than the biochemical assay for ER. The antibody to Ki67 recognizes the growth fraction of proliferating cells. We examined 100 primary breast cancers to investigate the relationship between ER status as measured by ERICA and Ki67 reactivity. Of the 56 ERICA positive cases, 47 (84%) were Ki67 negative whereas 30 of the 44 ERICA negative tumors were Ki67 positive (68%). There was evidence of a significant inverse relationship between ERICA and the growth fraction (77% of cases, p less than 0.001). In addition, a cluster of ERICA positive Ki67-positive tumors that were larger and occurred in older patients was identified as a subset that might require aggressive therapy. Our results suggest that Ki67 may be an important additional criterion for predicting the biological behaviour of breast cancers. PMID- 1495929 TI - The nested variant of transitional cell carcinoma: a neoplasm resembling proliferation of Brunn's nests. AB - This report describes four cases in which a malignant transitional cell neoplasm initially manifested as small nests and abortive tubules infiltrating the lamina propria. Many of the tumor cells were only slightly atypical but careful examination revealed at least some significantly anaplastic cells in every case, the degree of cellular atypia tending to parallel the depth of invasion. Despite the initial impression of a benign lesion resembling a proliferation of Brunn's nests, these carcinomas tended to be persistent and aggressive. PMID- 1495930 TI - Coronary artery embolism with special reference to invasive procedures as the source. AB - Since 1978, there have been sporadic reports of coronary artery embolism caused by cardiac catheterization, percutaneous transluminal coronary angioplasty, and other invasive procedures. To determine whether coronary artery embolism has increased with the wider application of such procedures, we searched for patients with coronary artery emboli among the autopsy cases with suspected acute myocardial infarction at the National Cardiovascular Center from 1977 to 1990. Of the 28 patients with emboli, 10% of the total autopsy cases of myocardial infarction was confirmed in 18. Infarction was diagnosed clinically in only six of these patients and directly caused the death of 11 of the 18 patients. In contrast to previous reports, where a minority of coronary emboli were caused by instrumentation, 14/28 patients in our series had coronary embolism due to invasive procedures, including eight patients with atheromatous emboli. half of the myocardial infarcts caused by embolism were hemorrhagic. Thus, coronary emboli are not so rare as once thought, and they may increase further with the progress of invasive diagnostic and surgical interventions. The possibility of coronary embolism thus needs to be kept in mind by all clinicians in the cardiovascular fields. PMID- 1495931 TI - Crescentic glomerulonephritis related to hepatitis B virus. AB - Crescentic glomerulonephritis was diagnosed in two chronic hepatitis B surface antigen carriers. In all three biopsies performed, hepatitis B e antigen was found in glomerular capillary tufts. The first patient presented with nephrotic syndrome and acute renal failure. The glomerular pathology revealed crescentic glomerulonephritis with endocapillary proliferation, and she recovered spontaneously with normal renal function over the following 6 mo despite a persistent hepatitis B surface antigenemia. The other patient presented with nephrotic syndrome and normal renal function. Hepatitis B virus-related membranous nephropathy was diagnosed on the first biopsy, and he did well on symptomatic treatment for 20 mo. The nephrotic syndrome recurred and subsequently he developed acute renal failure a month following interferon treatment. The repeated biopsy revealed a crescentic glomerulonephritis that was associated with mixed membranous and membranoproliferative glomerulopathies. This patient responded to immunosuppression and plasma exchange with residual impairment of renal function. He has been stable after 18 mo follow-up. PMID- 1495932 TI - CA 19-9 expression in subacute (de Quervain's) thyroiditis: an immunohistochemical study. AB - Carcinoma antigen 19-9 (CA 19-9) and carcinoembryonic antigen (CEA) expression was immunohistochemically investigated in 48 cases of subacute granulomatous (de Quervain's) thyroiditis, two of focal lymphocytic thyroiditis, three of Hashimoto's thyroiditis, two of Graves' disease, and seven follicular adenomas, 27 follicular carcinomas, and eight papillary carcinomas of the thyroid. CA 19-9 expression was found in all cases of subacute thyroiditis, lymphocytic thyroiditis, and papillary carcinomas examined and in approximately 50% of follicular adenomas and carcinomas. The strongest CA 19-9 staining was demonstrated in late stage subacute thyroiditis and in papillary carcinomas with marked sclerosis. Occasionally CA 19-9 expression was present in seemingly normal thyroid parenchyma adjacent to the thyroid lesions investigated. CEA was found in the center of the granulomatous lesions in acute stage subacute thyroiditis. All neoplasms were CEA negative. CA 19-9 and CEA could be demonstrated occasionally in multinucleated giant cells of subacute thyroiditis, which may suggest that these giant cells are of either histiocytic or follicular cell origin. Immunohistochemical investigation with antibodies against CA 19-9 and CEA may help to histomorphologically define subacute granulomatous thyroiditis. PMID- 1495933 TI - Histochemical reactivities of lectins and surfactant apoprotein in pulmonary adenocarcinomas and their metastases. AB - In an attempt to better understand the biologic behavior of neoplastic cell metastasis, a histochemical study with the use of six different lectins and a monoclonal antibody against human pulmonary surfactant apoprotein (PE-10) was carried out on primary adenocarcinomas of the lungs and their regional (usually lymphatic to lymph nodes or contralateral lung) and distant (usually hematogenous to extrathoracic organs) metastatic lesions of 54 postmortem cases. Primary pulmonary adenocarcinomas were classified further into acinar, papillary, and solid types according to WHO histological typing. Acinar type primary adenocarcinoma of the lungs showed significantly higher (p less than 0.05) binding reactions to Ricinus communis-I (RCA-I) and Ulex europaeus-I (UEA-I) lectins than solid type adenocarcinoma. With six different lectins, concordantly positive reactions between primary pulmonary adenocarcinomas and their lymphatic and hematogenous metastases were seen in 67% or more cases, and with soybean agglutinin (SBA) and UEA-I the concordance rates between primary and lymphatic metastases (lymph nodes and contralateral lungs, respectively) were significantly higher (p less than 0.05) than those between primary and hematogenous metastases. With PE-10 immunohistochemistry, concordantly positive reactions between primary and metastases were low, especially in cases of distant hematogenous metastases (25%), but the statistical significance of differences was missed by narrow margins. With alcian blue PAS-stain, concordantly positive reactions of mucin production between primary adenocarcinomas and both lymphatic and hematogenous metastases were high (92%), but there was no evidence of correlation between lectin bindings and alcian blue-PAS reactions to either primary or metastatic lesions of pulmonary adenocarcinomas. PMID- 1495934 TI - Localization of basic fibroblast growth factor and vascular endothelial growth factor in human glial neoplasms. AB - Fibroblast growth factors (FGFs) are widely recognized as a family of molecules that can influence cell proliferation and tissue neovascularization. Although the basic form of FGF (bFGF) has been found to enhance the growth of primary cell cultures made from human glial tumors, its exact role in vivo has been unclear. Likewise, vascular endothelial growth factor (VEGF) is a newly discovered addition to the growing list of angiogenic factors but, unlike bFGF, VEGF has a unique specificity for endothelial cells and possesses the properties required for secretion. In this study, we localized both basic FGF and VEGF in human gliomas to assess their possible role in the pathogenesis of these neoplasms. Retrospective analysis was performed using glial neoplasms that were fixed in 10% neutral buffered formalin and embedded in paraffin. The immunocytochemical procedures were performed using specific polyclonal antibodies raised against the amino terminus of bFGF and VEGF, respectively. Immunoreactive (IR) basic FGF was localized in normal, reactive, and neoplastic astrocytes as well as selected populations of normal neurons. IR VEGF, in contrast, was present primarily in neurons of normal brain, but was also found in both reactive and neoplastic astrocytes. In adjacent 4-microns tissue sections, strong immunoreactivity for VEGF and bFGF was found within the same populations of cells. In areas of endothelial proliferation, the strongest immunoreactivity for both growth factors was found within large anaplastic astrocytes that surrounded abnormal blood vessels. Our data support the hypothesis that VEGF may complement the actions of basic FGF in glial neoplasia. PMID- 1495935 TI - Detection of metastatic neuroblastoma in bone marrow biopsy specimens with an antibody to neuron-specific enolase. AB - To verify the practical utility of immunohistochemical analysis of bone marrow biopsy specimens in patients with neuroblastoma, we compared the results of routine histologic examination of 68 specimens with the results of immunohistochemical detection of tumor cells using an antibody to neuron-specific enolase (NSE). A commercially available polyclonal antibody to this enolase isoform consistently reacted with the neoplastic cells in biopsy specimens with histologic features diagnostic of (24 specimens) or suspicious for (one specimen) metastatic neuroblastoma. Immunohistochemical double-staining techniques documented that the NSE-positive neoplastic cells also reacted with antibodies to chromogranin and synaptophysin. Notably, anti-NSE detected small foci of metastatic neuroblastoma in two of 43 biopsy specimens that showed no evidence of metastatic tumor in the initial histologic sections. Rare NSE-reactive hematopoietic cells were present in approximately a third of the specimens with and those without neuroblastoma and were easily distinguished from metastatic tumor by morphologic examination. We conclude that this antibody to NSE consistently detects neuroblastoma cells in routinely processed bone marrow specimens, including small foci of tumor cells not evident in initial histologic sections. PMID- 1495936 TI - Neuroendocrine cells in colonic tumors. PMID- 1495937 TI - DNA quantitation by image analysis of paraffin-embedded colorectal adenocarcinomas and its prognostic value. AB - DNA content was measured by image analysis in a retrospective study of formalin fixed paraffin-embedded colorectal carcinomas from 213 patients who were followed up for at least 5 yr. DNA histograms were classified as diploid, aneuploid, or tetraploid. Diploid tumors comprised 29% of all cases, aneuploid 50%, and tetraploid 21%. Aneuploid tumors were found more often in patients with advanced disease and in carcinomas arising in the rectum. Pathologic stage, histologic grade, and ploidy were individually related to survival and recurrence. However, after stage stratification, histologic grade was no longer a significant prognostic factor. In patients without regional or distant metastases (Dukes' Stage A and Stage B), patients with aneuploid tumors had a statistically worse prognosis than patients with diploid or tetraploid tumors (P less than 0.01). The prognostic value of ploidy in this group of patients was maintained only in tumors arising in the distal colon and rectum (P less than 0.04). In patients with regional or distant metastases, DNA content did not provide additional prognostic information. In conclusion, DNA quantitation can be evaluated reliably by image analysis of archival material and can provide valuable prognostic information, especially in patients with Dukes' Stage A and Stage B disease. It may prove useful in guiding adjuvant therapy in these patients. PMID- 1495938 TI - Asymmetry in melanocytic lesions: a morphometric analysis. AB - The purpose of this study was to establish a morphometric technique that would approximate the subjective histological criteria of asymmetry in the diagnosis of malignant melanoma. The dermal and epidermal outlines of 52 consecutive malignant melanomas and 56 consecutive melanocytic nevi were digitized and analyzed for morphometric parameters of size, coordinates, and shape. The two parameters that showed the most significant discriminatory functions were the differences in the center of masses of the epidermal and dermal components in the horizontal dimension and the length of the longest segment in the lesion. PMID- 1495939 TI - High-grade squamous intraepithelial lesions and invasive carcinoma following the report of three negative Papanicolaou smears: screening failures or rapid progression? AB - The cytologic smears and histopathologic specimens of 18 patients developing cervical intraepithelial neoplasia 3 (CIN3) and two developing invasive squamous carcinoma following the report of at least three negative Papanicolaou tests were studied. A median number of 9.5 smears per patient procured over a median interval of 93.5 mo were reviewed. Twenty-eight (22.7%) of 123 reportedly negative smears revealed a squamous intraepithelial lesion (SIL), 17 (13.8%) were unsatisfactory, 14 (11.4%) lacked an endocervical component, and 37 (30.1%) were classified as atypical squamous cells of undetermined significance (ASQUS) on reexamination. Fourteen (50%) of 28 smears originally misclassified as negative contained fewer than 100 SIL cells and five (17.8%) were severely inflamed. One patient whose smears were misclassified as negative had an atrophic cervix, one had SIL cells primarily in thick sheets, and two had small CIN3 cells resembling squamous metaplasia. Six patients (30%) had a single false negative smear, seven (35%) had multiple false negative smears, seven (35%) had two or more unsatisfactory smears reported as negative, seven had at least two smears lacking an endocervical component, and six had at least two smears taken during pregnancy. Thirteen patients had abnormal smears classified as ASQUS or high grade SIL (HSIL) but never had a specimen showing only a low-grade SIL (LSIL). This study demonstrates that early signs of SIL may be difficult to recognize cytologically and that poor quality specimens and inadequate sampling may contribute to false negative diagnoses.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1495940 TI - Mast cell granules within endothelial cells: a possible signal in the inflammatory process? AB - Mast cell-endothelial cell interactions have long been suspected to be important in inflammation. The detail of the pathways of communication have yet to be elucidated. In this report we describe, for the first time, mast cell granules within endothelial cells of colonic capillaries in a patient with florid colitis, as well as rats with experimentally induced mast cell degranulation. We postulate that this phenomenon may occur more generally during immunologically mediated inflammatory cell degranulation, and may be one mechanism of communication to endothelium. PMID- 1495941 TI - Correspondence re: Kent Bottles, Mary J. Reznicek, Elizabeth A. Holly, David K. Ahn, Lester J. Layfield and Michael B. Cohen. Cytologic criteria used to diagnose adenocarcinoma in pleural effusions. Mod Pathol 4:677, 1991. PMID- 1495942 TI - Immunohistochemical characterization of ovarian borderline tumors of intestinal and mullerian types. AB - A panel of monoclonal antibodies (MAbs) including MOv2, MOv8, anti-CA 19-9, and anti-carcinoembryonic antigen (CEA), and a polyclonal antibody against CEA, was applied to three types of ovarian borderline tumors. The tumors included 19 intestinal-type mucinous borderline tumors (IMBTs), 22 endocervical-like mucinous borderline tumors (EMBTs), and 23 mixed-epithelial borderline tumors (MEBTs); the latter two tumors are of mullerian type. Statistically significant differences in the percentage of positive IMBTs compared to the mullerian tumors were seen for anti-CEA and MOv8; strikingly different staining patterns were also seen. IMBTs were more often and more diffusely CEA-positive than were the mullerian tumors; within the mullerian tumors, only one type of cell, the indifferent eosinophilic cell, was consistently CEA positive. The MAbs MOv2, MOv8, and anti-CA 19-9 showed more extensive positivity in the mullerian tumors than in the IMBTs. This study highlights the differences in cell types between IMBTs and these two types of mullerian borderline tumors. PMID- 1495943 TI - Monoclonal gammopathy of undetermined significance: a morphologic and immunophenotypic study of the bone marrow. AB - A monoclonal paraprotein in the serum or urine raises the possibility of myeloma. However, in a significant proportion of individuals with serum paraproteins, particularly those with low levels of paraprotein, clinical and routine bone marrow evaluation is not diagnostic of an underlying neoplasm. The purpose of this study was to define the pathologic basis for monoclonal gammopathy in patients whose bone marrow biopsies showed no evidence of myeloma. We used immunofluorescence microscopy and flow cytometry of cell suspensions prepared from aspirated marrow, as well as immunohistochemistry of core biopsies, to perform immunopathologic evaluations of the bone marrow from 26 such patients. Eighteen patients with myeloma and seven without a serum paraprotein or evidence of myeloma were similarly studied. The data indicate that 17 of the 26 patients with monoclonal paraproteins whose routine bone marrow biopsies were normal or nondiagnostic had, in fact, a dispersed monotypic plasma cell population of concordant immunoglobulin heavy and light chain type in the bone marrow demonstrable by at least one of the three analytic methods. Among these, immunofluorescence microscopy of isolated bone marrow mononuclear cells was the most sensitive assay. Immunophenotypic evaluation of the bone marrow is useful for documenting and quantifying a monoclonal plasma cell population in patients with monoclonal gammopathy of undetermined significance. PMID- 1495944 TI - The appendix in inflammatory bowel disease in children. AB - The morphologic characteristics of the colon in ulcerative colitis and Crohn's disease are well established, but specific appendiceal pathology is less clearly defined. In addition, the frequency of appendiceal involvement in children with inflammatory bowel disease has also not been delineated. We have determined the prevalence of appendiceal involvement in 41 children with inflammatory bowel disease (24 with Crohn's disease and 17 with ulcerative colitis) who required colonic resection and have defined the histopathologic characteristics of the appendix in these diseases. All appendices were abnormal. Specific changes of Crohn's disease or ulcerative colitis were observed respectively in 50% and 56% of the appendices in our patient population. Nonspecific changes only such as fibrous obliteration, serosal fibrosis and lymphoid and/or neuronal hyperplasia were noted in the remaining appendices. The severity of ileocolonic and appendiceal inflammation was similar in about two thirds of the patients with either type of inflammatory bowel disease. PMID- 1495945 TI - Computer-assisted image interpretation: use of a neural network to differentiate tubular carcinoma from sclerosing adenosis. AB - Measurement of nuclear and glandular size and shape features was carried out on 18 cases of sclerosing adenosis and 18 cases of tubular carcinoma. Modified Bonferroni analysis showed that glandular surface density and the coefficient of variation of luminal form factor were significant in discriminating between these two lesions. These two histologic features, together with the diagnosis, were used to train a neural network implementing a backpropagation algorithm. Following training, the network correctly classified 33 of the 36 cases in the training set (92%). Furthermore, the network correctly classified 19 of 19 cases in a test set consisting of cases that were not used to train the network. These results suggest that neural networks may be useful to assist in the differential diagnosis of histologically similar lesions. PMID- 1495946 TI - Genomic alterations in sarcomas: a histologic correlative study with use of oncogene panels. AB - Amplification and rearrangement of cellular proto-oncogenes are two of the several possible genetic alterations implicated in carcinogenesis and tumor progression. Although morphologically similar tumors may be heterogeneous at the level of the genome, some tumor types have shown relatively frequent and consistent abnormalities of specific oncogenes. In order to determine the frequency of oncogene amplification and rearrangement in several types of human sarcomas and to determine if histologically similar tumors have common genetic alterations, we analyzed 26 primary sarcomas by Southern hybridization. The oncogene probes utilized were N- and H-ras, sis, EGF-R (erb-B-1), neu (erb-B-2), fos, N- and c-myc, mos, and yes. The tumors studied included: five rhabdomyosarcomas (one alveolar, four embryonal), six malignant fibrous histiocytomas, six leiomyosarcomas, four liposarcomas, two Ewing's sarcomas, one osteosarcoma, and two fibrosarcomas. Oncogene abnormalities were identified in three tumors. One rhabdomyosarcoma showed 12-fold amplification and concurrent rearrangement of sis. This particular tumor also revealed rearrangement of H-ras and 15-fold amplification of c-myc. A second rhabdomyosarcoma revealed rearrangement of neu. A liposarcoma had a sis rearrangement. These findings suggest that many sarcomas show no common structural oncogene abnormalities. The presence of differing oncogene alterations within the rhabdomyosarcoma group indicates genetic heterogeneity among histologically similar sarcomas. The finding of a sis rearrangement in both a liposarcoma and a rhabdomyosarcoma, however, may suggest common oncogenesis among different tumor types. PMID- 1495947 TI - CEA immunoreactivity in metastatic malignant melanoma. AB - Immunohistochemical techniques may aid in the diagnosis of poorly differentiated metastatic tumors. Anti-carcinoembryonic antigen (CEA) antibodies have been used in the identification of epithelial neoplasms. However, recent unpublished data report CEA reactivity in malignant melanoma and melanoma cell lines. We studied 28 cases of known metastatic malignant melanoma with an antibody panel for CEA (polyclonal and monoclonal), AE1:3, S-100, and HMB-45. Reactivity for CEA (polyclonal) was seen in 15 of 28 (53%) cases: nine exhibited strong diffuse positivity, five moderate focal positivity, and one globular cytoplasmic staining. Focal reactivity for cytokeratin (AE1:3) was seen in three of 28 cases. HMB-45 staining was present in 23 of 28 (82%, including strong positivity in the cytokeratin-reactive cases). Staining for S-100 protein was strong in all cases. No staining was seen for CEA (monoclonal). CEA immunoreactivity is seen in a significant number of metastatic malignant melanoma cases. This may be due to CEA expression by tumor cells, or crossreactivity of the polyclonal antibody with substances such as nonspecific crossreacting antigen (NCA) that share antigenic sites with CEA. These findings emphasize the need for care in interpreting immunohistochemical results. Immunohistochemical evaluation of CEA should not be made alone, but only as part of a diagnostic antibody panel. PMID- 1495948 TI - The relationships among tumor-infiltrating lymphocytes, histopathologic findings, and long-term clinical follow-up in renal cell carcinoma. AB - The relative abundance of tumor-infiltrating mononuclear cells (TIM) was retrospectively evaluated by immunohistology in nephrectomy specimens from 24 cases of human renal cell carcinoma (RCC). The extent of T-lymphocyte (T-cell) and B-lymphocyte (B-cell) infiltration of the tumors was graded semiquantitatively (0 to 4) in each case. Results of this analysis were correlated with clinical evidence of recurrent RCC, histologic evidence of venous invasion, tumor necrosis, and histologic cell type. Clinical follow-up demonstrated the presence of recurrent tumors in four of the 24 cases (17%), and these cases correlated with higher stage and pathologic grade tumors, as well as significantly increased TIM. Venous invasional and tumor necrosis correlated directly with tumor size, pathologic grade, and extent of TIM. Venous invasion was also associated with advanced stage. The group of cases with mixed or granular histologic cell type was associated with advanced stage, high pathologic grade, and increased T-cell infiltration compared to the clear-cell group of tumors. Overall, the pathologic grade demonstrated the highest correlation coefficients with clinical and TNM stage, but also correlated directly with the extent of T-cell infiltration of the tumor. These results confirm previous findings demonstrating a correlation in RCC between increased T-cell infiltration and both high clinical stage and pathologic grade. In addition, increased T-cell infiltration was found to correlate with tumor recurrence, indicating that such infiltration, along with high pathologic grade, is another indicator of poor prognosis in RCC. PMID- 1495949 TI - Papillary serous adenocarcinoma of the uterine cervix: a report of three cases. AB - Three cases of primary papillary serous adenocarcinoma of the uterine cervix, the first described in detail at this site, are reported. Two women, 32 and 33 years of age, presented with postcoital spotting. The third patient, a 69-year-old asymptomatic woman, had abnormal cells on a routine cervical Papanicolaou smear. There was no evidence of extracervical spread on physical examination in any of the cases, but computed tomographic scan of the abdomen revealed retroperitoneal lymphadenopathy in one patient. Two patients, one treated by preoperative radiation and cervicectomy and the other by radical hysterectomy and postoperative radiation, are alive and well 5 years later. The third patient underwent cone biopsy and is currently completing chemotherapy to be followed by radiation therapy. On gross examination, the tumors were indistinguishable from typical endocervical adenocarcinoma. Microscopic examination revealed high-grade papillary serous adenocarcinoma in each case; in one tumor, there was a minor admixed component of low-grade villoglandular papillary adenocarcinoma. Although none of the tumors was deeply invasive, pelvic nodal metastases were present in two cases. There was no evidence of endometrial, tubal, ovarian, or peritoneal tumor in any case. Papillary serous carcinomas should be distinguished from other papillary carcinomas of the cervix, particularly the recently described low-grade papillary villoglandular adenocarcinoma, a variant of endocervical adenocarcinoma with a good prognosis. PMID- 1495950 TI - Amyloid plaque: morphology, evolution, and etiology. PMID- 1495951 TI - The copper-peroxide-silver method: a highly sensitive procedure for the demonstration of Alzheimer's disease lesions and for signal intensification in immunocytochemistry. AB - Ammoniacal silver solutions give striking impregnation of Alzheimer's disease (AD) lesions if sections are pretreated with copper sulfate and hydrogen peroxide. In contrast to most silver impregnation methods, no staining of normal neurites is obtained, and senile plaques (SPs), neurofibrillary tangles (NFTs), and neuropil threads (NTs) are strongly stained in black against a clear background. A sodium acetate wash interposed between the copper sulfate and hydrogen peroxide resulted in suppression of the staining of amyloid lesions. This variant of the basic procedure (CPS-II method), maintains the capacity of the latter (CPS-I method) to strongly impregnate NFTs and NTs. In addition, it clearly delineates the dystrophic neurites of SPs obscured by the strong argyrophilia of the amyloid deposits seen in CPS-I stains. NTs are strongly impregnated with both CPS-I and CPS-II methods and are unmasked from normal neurites, which remain unstained. The staining can be abolished by pretreatment with formic acid and erased with a brief wash in sulfochromic acid. Destained sections can be restained with either method or with immunoperoxidase procedures. CPS staining of previously immunostained tissues produces marked intensification of the diaminobenzidine reaction product. In AD brains, the immunostaining is markedly enhanced and selective when the silver procedure is preceded by formic acid treatment. The selectivity and high sensitivity of the procedure may be useful as a diagnostic tool and of value to study the biogenesis and natural evolution of the brain lesions of AD.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1495952 TI - Alkaptonuria and renal failure: a case report and review of the literature. AB - In alkaptonuric ochronosis, the absence of homogentisic acid oxidase results in the accumulation of homogentisic acid in the body. Associated renal failure is rare and usually occurs in the later stages of the disease. We report a 19-yr-old girl who presented initially with severe renal failure, without family or past history of illness. There was no significant proteinuria or hematuria. No clinical evidence of pigmentation such as skin and subcutaneous cartilages was noted. However, pigment deposits were identified in the renal biopsy specimens obtained within a week after admission and another after a month. Two months later the peritoneal dialysis fluid and skin progressively darkened, suggesting ochronosis. This was confirmed by the detection of homogentisic acid in the serum and urine. The patient expired in renal failure. Renal biopsy tissues showed diffuse chronic tubulo-interstitial disease characterized by widespread tubular atrophy, interstitial fibrosis, and a moderate degree of inflammation. Many tubular cells contained brown, coarsely granular ochronotic pigment (OP) and a few pigment casts were in the lumina. Similar deposits were also in the interstitium and within histiocytes. Ultrastructural studies of the glomeruli revealed small sparse OP deposits in the visceral and parietal epithelial cells, mesangial cells, and rare extracellular and basement membrane deposits. The tubulointerstitial changes were varied: atrophy and dilatation of tubules, varying degrees of lysosomal OP and degeneration of tubular cells, casts containing OP with crystalline material, histiocytes distended with OP, and free interstitial pigment deposition.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1495953 TI - Correspondence re: A. B. Ackerman, R. Sood, and M. Koenig, Primary acquired melanosis of the conjunctiva is melanoma in situ. Mod Pathol 4:253, 1991. PMID- 1495954 TI - Correspondence re: G. A. Herrera, W. W. Johnson, V. G. Lockard, and B. L. Walker, Soft tissue myofibroblastoma. Mod Pathol 4:571, 1991. PMID- 1495955 TI - Redesigning the DNA-binding specificity of a zinc finger protein: a data base guided approach. PMID- 1495956 TI - NADPH-dependent beta-oxidation of unsaturated fatty acids with double bonds extending from odd-numbered carbon atoms. AB - The mitochondrial metabolism of 5-enoyl-CoAs, which are formed during the beta oxidation of unsaturated fatty acids with double bonds extending from odd numbered carbon atoms, was studied with mitochondrial extracts and purified enzymes of beta-oxidation. Metabolites were identified spectrophotometrically and by high performance liquid chromatography. 5-cis-Octenoyl-CoA, a putative metabolite of linolenic acid, was efficiently dehydrogenated by medium-chain acyl CoA dehydrogenase (EC 1.3.99.3) to 2-trans-5-cis-octadienoyl-CoA, which was isomerized to 3,5-octadienoyl-CoA either by mitochondrial delta 3,delta 2-enoyl CoA isomerase (EC 5.3.3.8) or by peroxisomal trifunctional enzyme. Further isomerization of 3,5-octadienoyl-CoA to 2-trans-4-trans-octadienoyl-CoA in the presence of soluble extracts of either rat liver or rat heart mitochondria was observed and attributed to a delta 3,5,delta 2,4-dienoyl-CoA isomerase. Qualitatively similar results were obtained with 2-trans-5-trans-octadienoyl-CoA formed by dehydrogenation of 5-trans-octenoyl-CoA. 2-trans-4-trans-Octadienoyl CoA was a substrate for NADPH-dependent 2,4-dienoyl-CoA reductase (EC 1.3.1.34). A soluble extract of rat liver mitochondria catalyzed the isomerization of 2 trans-5-cis-octadienoyl-CoA to 2-trans-4-trans-octadienoyl-CoA, which upon addition of NADPH, NAD+, and CoA was chain-shortened to hexanoyl-CoA, butyryl CoA, and acetyl-CoA. Thus we conclude that odd-numbered double bonds, like even numbered double bonds, can be reductively removed during the beta-oxidation of polyunsaturated fatty acids. PMID- 1495957 TI - Conservation of the prohormone convertase gene family in metazoa: analysis of cDNAs encoding a PC3-like protein from hydra. AB - A subclass of proteolytic enzymes that correctly cleave precursor proteins at paired basic residues and are structurally related to the bacterial subtilisins has recently been identified. In yeast, a single membrane-bound proteolytic processing enzyme encoded by the kex2 gene has been found, whereas in higher vertebrates cDNAs encoding four distinct enzymes (PC2, PC3, furin, and PACE 4) have been identified. Like kex2, furin (also known as PACE) contains a hydrophobic transmembrane domain, but PC2, PC3, and PACE 4 lack this feature. All five enzymes exhibit striking similarities in their catalytic domains, and this suggests that they have arisen from a common ancestral subtilisin-like gene. We report here the identification of cDNAs encoding a protein that is similar in structure to PC3 from a simple metazoan, Hydra vulgaris (formerly Hydra attenuata). cDNAs encoding two isoforms of this PC3-like enzyme were obtained that differ only in their carboxyl-terminal sequences, probably due to alternative splicing of a common pre-mRNA. Neither form contains a transmembrane domain. Predicted amino acid sequence comparisons revealed that the hydra PC3 like enzyme is 55.4% and 56.7% identical in the catalytic domain to mouse PC3 and human furin, respectively. RNA blot analyses revealed that the PC3-like RNA is expressed predominantly in the hydra body column and not in the head region, although the hydra head contains a high density of nerve cells, which synthesize a variety of neuropeptides. For this reason, we suspect that another proprotein cleavage enzyme isoform may be expressed in head nerve cells. The isolation of a PC3-like cDNA from hydra is consistent with the presence of neuroendocrine cells and indicates that the PC/furin gene family has been well conserved in all metazoa. A simplified nomenclature for the group of mammalian processing proteases is proposed. PMID- 1495958 TI - Evolution of the major histocompatibility complex: isolation of class II A cDNA clones from the cartilaginous fish. AB - Along with the T-cell receptor and immunoglobulin, the major histocompatibility complex (MHC) plays a key role in mounting immune responses to foreign antigen. To gain insights into the evolution of the MHC, class II A cDNA clones were isolated from nurse sharks, a member of the class of cartilaginous fish. Two closely related cDNA clones, which might encode allelic products, were identified; of the three amino acid substitutions found in the alpha 1 domain, two were located at positions postulated to interact with processed peptides. The deduced nurse shark MHC class II alpha chains showed conspicuous structural similarity to their mammalian counterparts. Isolation of cDNA clones encoding typical MHC class II alpha chains was unexpected since no direct evidence for T cell-mediated immune responses has been obtained in the cartilaginous fish. The cartilaginous fish is phylogenetically the most primitive class of vertebrates from which any MHC gene has been isolated. PMID- 1495959 TI - gp330 associates with a 44-kDa protein in the rat kidney to form the Heymann nephritis antigenic complex. AB - Using antibodies isolated from glomeruli of nephritic rats we have previously identified a 330-kDa cell surface glycoprotein (gp330) as a major pathogenic antigen of Heymann nephritis (HN), an experimental model of human membranous glomerulonephritis. Recently, we have isolated a cDNA clone, C14, encoding a polypeptide that contains a pathogenic epitope of HN responsible for the initiation of the disease. Subsequently, another protein, alpha 2-macroglobulin receptor-associated protein (alpha 2-MRAP), which is a subunit of the receptor for human alpha 2-macroglobulin/low density lipoprotein receptor-related protein (LRP), was shown to possess a high degree of sequence homology to the C14 protein (C14p). In this report, we have investigated the relationship between gp330, C14p, and alpha 2-MRAP. Immunoprecipitation studies demonstrate that gp330 forms a heterodimeric association with a 44-kDa polypeptide that is stable to detergent extraction and long-term centrifugation. Further, immunoblotting analysis on the purified complex indicates that the 44-kDa associated protein shares immunological identity to C14p and alpha 2-MRAP. In addition, antibodies eluted from glomeruli of HN rats and antibodies to a C14 fusion protein immunoprecipitated gp330 and the 44-kDa protein, demonstrating that the epitopes responsible for the initial events of HN are accessible within the complex. Based on these data, three models are proposed to explain how pathogenic epitopes in the gp330-44-kDa, HN antigenic complex may be presented at the cell surface and initiate the onset of HN. PMID- 1495960 TI - Fluorescence-activated sorting of totipotent embryonic stem cells expressing developmentally regulated lacZ fusion genes. AB - Murine embryonic stem (ES) cells were infected with a retrovirus promoter trap vector, and clones expressing lacZ fusion genes (LacZ+) were isolated by fluorescence-activated cell sorting (FACS). Of 12 fusion genes tested, 1 was repressed when ES cells were allowed to differentiate in vitro. Two of three lacZ fusion genes tested were passed into the germ line, indicating that FACS does not significantly affect stem cell totipotency. The pattern of lacZ expression observed in vivo was consistent with that seen in vitro. Both fusion genes were expressed in preimplantation blastulas. However, a fusion gene whose expression was unaffected by in vitro differentiation was ubiquitously expressed in day-10 embryos, while the other, which showed regulated expression in vitro, was restricted to cells located along the posterior neural fold, the optic chiasm, and within the fourth ventricle. These results demonstrate the utility of using promoter trap vectors in conjunction with fluorescence sorting to disrupt developmentally regulated genes in mice. PMID- 1495962 TI - Coregulation of purine and histidine biosynthesis by the transcriptional activators BAS1 and BAS2. AB - We have found cross-pathway regulation between purine and histidine biosynthesis in yeast. The transcription factors BAS1 and BAS2/PHO2, which are also regulators of the histidine pathway, participate in the regulation of the purine biosynthetic pathway. Analysis of four genes of the purine pathway (ADE1, ADE2, ADE5,7, and ADE8) shows that their expression is repressed by adenine. The maximal basal and induced expression of these purine genes requires the presence of both BAS1 and BAS2. The factor BAS1 has been shown to bind at a site containing the TGACTC hexanucleotide motif in the ADE2 and ADE5,7 promoters. This motif is required for both basal and induced activation of the ADE2 gene by BAS1 and BAS2. PMID- 1495961 TI - At least three promoters direct expression of the mouse glucocorticoid receptor gene. AB - We have characterized the gene for the mouse glucocorticoid receptor. The gene spans approximately 110 kilobases, and glucocorticoid receptor transcripts are assembled from nine exons. Expression of the gene is controlled by at least three promoters, resulting in glucocorticoid receptor transcripts with different 5' nontranslated exons. One promoter is cell-specific, found to be active only in T lymphocytes. The other two promoters are active to various degrees in all cell lines and tissues so far analyzed and are located in a CpG island. The promoter activities are accompanied by DNase I hypersensitivity sites in chromatin. In contrast to a conservation of exon-intron structure, differences in promoter organization suggest a divergence between the evolution of regulatory and coding regions among members of the steroid receptor super-family. PMID- 1495963 TI - Detection of DNA domains in Drosophila, human, and plant chromosomes possessing mainly 50- to 150-kilobase stretches of DNA. AB - We have used pulsed-field gel electrophoresis of undigested DNA prepared by cell lysis in agarose with proteinase K detergent treatment and found a resolvable DNA fraction, denoted forum DNA (f-DNA). By changing the pulsed-field gel pulse length from 25 to 4500 sec, to obtain optimal separation in different ranges, we have found f-DNA to occupy a rather broad zone from 2 megabases to 10 kilobases (kb), but mainly at a range between 50 and 150 kb. f-DNA seems to appear as a result of nonrandom spontaneous degradation during cell treatment. The terminal regions of f-DNA segments have been cloned by using a jumping library. The molecular analysis of unique DNA sequence from an anonymous Drosophila DNA segment led to the conclusion that f-DNA appears as a result of nonrandom chromosomal DNA cleavage within sensitive regions that occupy a few kilobases. This conclusion was confirmed by detection of rather discrete hybridization bands on pulsed-field gel Southern blots in a region of good separation of undigested f DNA after hybridization with different unique and repetitive probes. We propose that f-DNA segments may correspond to some regular higher-order structures in the eukaryotic chromosomes. PMID- 1495964 TI - Attenuation of sensory receptor signaling by covalent modification. AB - The Tar receptor is a transmembrane protein that regulates bacterial chemotaxis in response to changes in the level of aspartic acid in the medium. The extracellular portion of the protein can bind aspartate, and the cytoplasmic portion modulates CheA kinase activity. The receptor can either activate or inhibit the kinase. The cytoplasmic portion of the receptor can be modified by carboxymethylation of specific glutamic acid residues. To test the effects of differential methylation on receptor function, we prepared membranes from cells that have specifically modified forms of the receptor and tested the relative ability of each of these forms to activate or inhibit CheA kinase. Completely demethylated receptor was a potent inhibitor and poor activator of the kinase, while the fully modified receptor was an excellent activator but an inefficient inhibitor. Partially modified receptor could act both as an effective inhibitor and as an activator. Reversible modification provides a mechanism that allows the cell to accumulate a population of receptor molecules capable of generating a wide range of signaling intensities. PMID- 1495965 TI - The crtE gene in Erwinia herbicola encodes geranylgeranyl diphosphate synthase. AB - A cluster of genes essential for the biosynthesis of carotenoids in Erwinia herbicola has been isolated and characterized [Armstrong, G.A., Alberti, M. & Hearst, J. E. (1990) Proc. Natl. Acad. Sci. USA 87, 9975-9979]. Related gene clusters are found in other carotenoid-producing bacteria. Two of these genes, crtB and crtE, have been assigned to enzymes responsible for conversion of geranylgeranyl diphosphate (GGPP) to prephytoene diphosphate and prephytoene diphosphate to phytoene, respectively. We isolated crtE from the Er. herbicola cluster by PCR amplification and cloned the coding region into the Escherichia coli expression vector pARC306N. Es. coli JM101 was transformed with the expression plasmid, and transformants were assayed for GGPP synthase and phytoene synthase activity. Extracts from JM101/pSM145 accumulated [14C]GGPP when incubated with [14C]isopentenyl diphosphate and farnesyl diphosphate, whereas similar incubations with [3H]GGPP did not yield prephytoene diphosphate or phytoene. Thus, crtE encodes GGPP synthase. PMID- 1495967 TI - Copper deficiency reversibly impairs DNA synthesis in activated T lymphocytes by limiting interleukin 2 activity. AB - The essentiality of adequate copper (Cu) nutriture for normal T-cell function in laboratory and domestic animals is well established. However, specific biochemical roles of Cu in the maturation and activation of T cells have not been defined. Previous work showed that when cultures of splenic mononuclear cells (MNCs) from Cu-deficient rats were exposed to T-cell mitogens, DNA synthesis was markedly reduced despite normal up-regulation of interleukin 2 (IL-2) receptors, transferrin receptors, and class II major histocompatibility complex molecules. In the present study, IL-2 activity in PHA-treated cultures of MNCs from Cu deficient rats was 40-50% that of controls as determined by bioassay. Addition of rat IL-2 to phytohemagglutinin-treated cultures of MNCs from Cu-deficient rats increased blastogenic activity to control levels, demonstrating that Cu deficiency does not inhibit transition of quiescent cells to the competence phase of the activation process. Moreover, supplementation of MNC cultures from Cu deficient rats with physiological levels of Cu enhanced IL-2 activity and DNA synthesis in response to phytohemagglutinin. These data indicate that IL-2 activity in cultures of activated splenic T lymphocytes from Cu-deficient rats is insufficient for optimal blastogenesis. PMID- 1495966 TI - Clonal evolution of a follicular lymphoma: evidence for antigen selection. AB - The potential role antigens play in growth stimulation or in clonal selection of follicular lymphomas is unknown. To study this issue, we sequenced the immunoglobulin heavy chain variable region genes expressed by a follicular lymphoma from multiple biopsy specimens and also cloned and sequenced the corresponding germ-line variable gene from this patient. Comparison to the germ line gene revealed numerous nucleotide substitutions in all of the lymphoma variable gene sequences. Some of the substitutions may have occurred in the nonmalignant precursor B cell that gave rise to this lymphoma because they were shared among all of the variable genes, but many of the mutations accumulated as the malignant clone expanded. The mutations were distributed in such a way that strongly suggested the majority of tumor cells had been positively selected through their antigen receptor. This was especially evident for the mutations that developed late in the clonal evolution of this lymphoma. These findings indicate that antigen stimulation may be involved in the growth of follicular lymphoma tumors. PMID- 1495968 TI - Entropic stabilization of a mutant human lysozyme induced by calcium binding. AB - The stabilization mechanism of the mutant human lysozyme with a calcium binding site (D86/92) was investigated by using calorimetric approaches. By differential scanning calorimetry, the enthalpy change (delta H) in the unfolding of holo D86/92 was found to be 6.8 kcal/mol smaller than that of the wild-type and apo D86/92 lysozymes at 85 degrees C. However, the unfolding Gibbs energy change (delta G) of the holo mutant was 3.3 kcal/mol greater than the apo type at 85 degrees C, indicating a significant decrease of entropy (T delta S = 10.1 kcal/mol) in the presence of Ca2+. Subsequently, the Ca2+ binding process in the folded state of the mutant was analyzed by using titration isothermal calorimetry. The binding enthalpy change was estimated to be 4.5 kcal/mol, and delta G was -8.1 kcal/mol at 85 degrees C, which indicates that the binding was caused by a large increase in entropy (T delta S = 12.6 kcal/mol). From these analyses, the unfolded holo mutant was determined to bind Ca2+ with a binding delta G of -4.8 kcal/mol (delta H = -2.6 kcal/mol, T delta S = 2.2 kcal/mol) at 85 degrees C. Therefore, the major cause of stabilization of holo-D86/92 is the decrease in entropy of the peptide chain due to Ca2+ binding to the unfolded protein. PMID- 1495969 TI - A hybrid plant RNA virus made by transferring the noncapsid movement protein from a rod-shaped to an icosahedral virus is competent for systemic infection. AB - For many plant RNA viruses, multiple viral gene products, including noncapsid movement proteins and capsid proteins, contribute to the spread of infection within plants. The extent to which these factors interact to support infection spread is not known, but, for movement protein mutants of certain viruses, the inability of coinoculated "helper" viruses to complement defective movement has suggested a possible requirement for coadaptation between noncapsid movement proteins and other virus factors. To test directly for required coadaptation, the 3a movement protein gene of cowpea chlorotic mottle virus, an icosahedral bromovirus, was replaced with the nonhomologous 30-kDa movement protein gene of sunn-hemp mosaic virus, a rod-shaped, cowpea-adapted tobamovirus. The resulting hybrid virus is competent for systemic infection of cowpea, with systemic infection dependent upon expression of the 30-kDa gene. In view of the dramatic differences between cowpea chlorotic mottle virus and sunn-hemp mosaic virus in genetic organization and particle morphology, the ability of the hybrid to systemically infect cowpea implies that the tobamovirus 30-kDa movement protein functions independently of sequence-specific interactions with other viral components or sequences. Similarly, the required contribution of bromovirus capsid protein to infection movement appears to be independent of specific interaction with the natural 3a movement protein. In addition to other implications concerning movement protein and coat protein function, the results are consistent with the possibility that two or more distinguishable transfer processes may be involved in crossing different tissue barriers to achieve full systemic spread of infection. PMID- 1495970 TI - Song presentation induces gene expression in the songbird forebrain. AB - We investigated the participation of genomic regulatory events in the response of the songbird brain to a natural auditory stimulus of known physiological and behavioral relevance, birdsong. Using in situ hybridization, we detected a rapid increase in forebrain mRNA levels of an immediate-early gene encoding a transcriptional regulator (ZENK; also known as zif-268, egr-1, NGFI-A, or Krox 24) following presentation of tape-recorded songs to canaries (Serinus canaria) and zebra finches (Taeniopygia guttata). ZENK induction is most marked in a forebrain region believed to participate in auditory processing and is greatest when birds hear the song of their own species. A significantly lower level of induction occurs when birds hear the song of a different species and no induction is seen after exposure to tone bursts. Cellular analysis indicates that the level of induction reflects the proportion of neurons recruited to express the gene. These results suggest a role for genomic responses in neural processes linked to song pattern recognition, discrimination, or the formation of auditory associations. PMID- 1495971 TI - Carbonic anhydrase IV on brain capillary endothelial cells: a marker associated with the blood-brain barrier. AB - Carbonic anhydrase (CA) activity plays an important role in controlling cerebrospinal fluid production and also influences neuroexcitation and susceptibility to seizures. Until recently, CA II was the only CA demonstrated in brain. Its distribution is limited to the epithelial cells of the choroid plexus and to the myelin-forming cells, the oligodendrocytes. In this report, we present immunoblots, using an antibody raised to CA IV from rat lung, that show that CA IV is also present in rat and mouse brain. Results of immunohistochemistry and immunoelectron microscopy on sections from rat and mouse brain are presented that show the distribution of CA IV to be quite distinct from that of CA II. CA IV is expressed on and is limited to the luminal surface of endothelial cells of cerebral capillaries. These results establish CA IV as a cytochemical marker associated with the blood-brain barrier and suggest an important role for CA IV in CO2 and HCO3- homeostasis in brain. PMID- 1495972 TI - Yeast glycoprotein biosynthesis: MNT1 encodes an alpha-1,2-mannosyltransferase involved in O-glycosylation. AB - The Saccharomyces cerevisiae MNT1 gene encodes a Golgi mannosyltransferase. Gene disruption of the MNT1 locus leads to a greater than 90% reduction of specific alpha-1,2-mannosyltransferase activity with alpha-methylmannoside as acceptor. Null mutants of MNT1 are viable, have no apparent growth defect, and are blocked in the elongation of protein O-linked mannobiose. Structural analysis of the N linked outer chain isolated from an mnn1 mnn10 mnt1 strain revealed no alteration in carbohydrate structure compared to the parental mnn1 mnn10 strain. The MNT1 gene is identical to KRE2, and mutations in the gene render cells resistant to the killer toxin K1 of S. cerevisiae, which suggests a role for O-mannosylated proteins in the resistance mechanism. In addition, MNT1 is part of a multigene family whose members are presumed to be yeast Golgi mannosyltransferases. PMID- 1495973 TI - Evolution of the mouse t haplotype: recent and worldwide introgression to Mus musculus. AB - Mouse t haplotypes are variants of chromosome 17, consisting of four inversions. Despite the homozygous lethality and pleiotropic effect on embryonic development, sperm production, and recombination, they have widely spread in natural populations of the house mouse (10-40% in frequency) because of the meiotic drive advantage. We sequenced 14 Tcp-1 (t-complex polypeptide 1) genes from four t haplotypes, nine wild mice, and a rat as a reference. From a comparison of intron sequences of 610 base pairs, we dated the origin of t haplotypes to 2.9 +/- 0.7 million years ago, which predates the splitting of Mus musculus subspecies (approximately 1 million years ago). However, the Tcp-1 intron sequences of t haplotypes from different M. musculus subspecies from various parts of the world show no divergence, indicating the recent introgression (no earlier than 0.8 million years ago) of a single ancestral type. Nucleotide changes in coding regions are also consistent with this conclusion. Hence, polymorphisms among t haplotypes including lethality factors have accumulated during this short time period independently in each M. musculus subspecies. PMID- 1495974 TI - pokkuri, a Drosophila gene encoding an E-26-specific (Ets) domain protein, prevents overproduction of the R7 photoreceptor. AB - Studies on sevenless and bride of sevenless genes have revealed that the R8 cell plays a key role in the fate of the R7 photoreceptor cell, presenting on its surface an inductive cue to which R7 responds. sev-independent induction of R7 cells has been reported in the seven-up mutation, which appears to transform R1 and R6 cells to R7 cells. We have induced recessive mutations in a gene pokkuri (pok; pokkuri is a Japanese word that means "dropping dead") that lead to overproduction of R7 cells with rather minor effects on outer photoreceptors and R8 cells. Pok protein may function as a transcription factor, as the predicted amino acid sequence contains a region similar to the consensus established for the E-26-specific (Ets) domain. PMID- 1495975 TI - Tissue- and site-specific DNA recombination in transgenic mice. AB - We have developed a method of specifically modifying the mammalian genome in vivo. This procedure comprises heritable tissue-specific and site-specific DNA recombination as a function of recombinase expression in transgenic mice. Transgenes encoding the bacteriophage P1 Cre recombinase and the loxP-flanked beta-galactosidase gene were used to generate transgenic mice. Genomic DNA from doubly transgenic mice exhibited tissue-specific DNA recombination as a result of Cre expression. Further characterization revealed that this process was highly efficient at distinct chromosomal integration sites. These studies also imply that Cre-mediated recombination provides a heritable marker for mitoses following the loss of Cre expression. This transgene-recombination system permits unique approaches to in vivo studies of gene function within experimentally defined spatial and temporal boundaries. PMID- 1495976 TI - Mutations induced by methylene blue plus light in single-stranded M13mp2. AB - Reactive oxygen species are generated by a variety of cellular processes. These endogenously generated, reactive intermediates produce a multiplicity of DNA alterations and mutations and have been implicated in the pathogenesis of several human diseases. We report here that treatment of single-stranded M13mp2 bacteriophage DNA with methylene blue and white light generates increased levels of 8-hydroxydeoxyguanosine and that mutagenesis is both highly specific and dependent on the SOS response. Lesions produced block the progression of DNA synthesis one base preceding template guanines. In SOS-induced Escherichia coli, 97% of all methylene blue-induced mutations in the lacZ alpha gene of M13mp2 DNA are single-base substitutions opposite template guanines. The most frequent mutations are G----C transversions. The G----T transversions expected from the presence of 8-hydroxydeoxyguanosine in the template strand occur, but at a lower frequency. Sequence data together with SOS dependency and the presence of replication blockage demonstrate that while 8-hydroxydeoxyguanosine may serve as an important marker to monitor oxygen-induced DNA damage in humans, it does not account for either the observed blockage to replication or the mutagenesis by methylene blue plus light in SOS-induced E. coli. Instead, an as yet unidentified lesion generated by active oxygen species is a more potent mutagenic event. PMID- 1495977 TI - Secretion of a soluble, chimeric gamma delta T-cell receptor-immunoglobulin heterodimer. AB - Soluble derivatives of T-cell antigen receptors (TCRs) should prove invaluable for studying the interaction of these receptors with antigens and major histocompatibility complex molecules, for structural studies, and for the identification of unknown ligands. We have engineered chimeric proteins, containing the extracellular domains of the mouse V gamma 1.1-C gamma 4 and V delta 6.2-C delta (V, variable; C, constant) TCR chains fused to the hinge region, CH2 (H, heavy), and CH3 domains of human IgG1 heavy chain, and expressed them by transient transfection in COS cells. We show here that TCR gamma-IgH and TCR delta-IgH chimeric chains are produced intracellularly in significant amounts, that the two chains can assemble correctly to form disulfide-linked, glycosylated heterodimers, and that a selective mechanism allows secretion of correctly paired receptor chains into the medium. Identity of the chimeric secreted TCR gamma delta-IgH heterodimer was confirmed by immunoblot analysis using V gamma 1-specific anti-peptide antiserum and immunoprecipitation analysis using the monoclonal antibody UC7, which is shown to be specific for the TCR delta chain. In addition, the soluble TCR gamma delta-IgH heterodimer can be immunoprecipitated with the anti-clonotypic monoclonal antibody F10/56, which suggests that the fusion protein likely has a structural conformation similar to that of the native TCR. The COS cell expression system may prove useful for the production of additional TCR-IgH fusion proteins. PMID- 1495978 TI - Aminoguanidine inhibits oxidative modification of low density lipoprotein protein and the subsequent increase in uptake by macrophage scavenger receptors. AB - Aminoguanidine decreases the formation of advanced glycosylation end products that occurs during chronic hyperglycemia. Presumably this occurs because early glycosylation products preferentially bind to aminoguanidine rather than to lysine groups of adjacent proteins. Because oxidative modification of low density lipoprotein (LDL) also involves derivatization of lysine residues of apolipoprotein (apo) B by reactive aldehydes formed during the decomposition of oxidized fatty acids, we postulated that aminoguanidine might also inhibit the oxidatively induced modification of LDL protein. To test this hypothesis we oxidized LDL by incubation with Cu2+ or with endothelial cells in the absence or presence of aminoguanidine. Aminoguanidine prevented apo B lysine modification, as measured by fluorescence spectroscopy, and inhibited in a dose-dependent manner the oxidatively induced increase in subsequent macrophage uptake. At concentrations that inhibited apo B modification (5-10 mM), aminoguanidine increased the lag time in diene conjugation but did not affect the plateau value reached. These data indicate that aminoguanidine inhibits oxidative modification of LDL protein in large part by binding reactive aldehydes formed during lipid peroxidation and preventing their subsequent conjugation to apo B. Thus, aminoguanidine (and related compounds) may be of dual benefit in inhibiting atherosclerosis, both by inhibiting formation of advanced glycosylation end products and by inhibiting the modification of LDL apo B that makes it a ligand for scavenger receptors. PMID- 1495979 TI - The two-step conversion of big endothelin 1 to endothelin 1 and degradation of endothelin 1 by subcellular fractions from human polymorphonuclear leukocytes. AB - The metabolism of big endothelin 1 (bET) and endothelin 1 (ET-1) by subcellular fractions from human polymorphonuclear leukocytes (PMNs) was investigated by bioassay and reversed-phase high-performance liquid chromatography. More than 80% of endothelin-converting activity was recovered from the cytosolic fraction, which in addition to ET-1 generated other peptides from bET. The processing of bET to all its metabolites including ET-1 was prevented by the serine protease inhibitor 3,4-dichloroisocoumarin (DCI; 50 microM) or the elastase inhibitor ONO 5046 (100 microM) but not by phenylmethylsulfonyl fluoride (PMSF; 143 microM), another serine protease inhibitor. Paradoxically, human leukocyte elastase, despite generating a bET fragmentation pattern similar to that of PMN cytosol, produced very little ET-1. However, subsequent treatment of the elastase-derived metabolites of bET with PMN cytosol in the presence of ONO-5046 dramatically increased the amount of ET-1 formed. The generation of ET-1 following this intervention was inhibited by DCI. The PMN membrane preparation degraded ET-1 to a major metabolite, similar to that produced from ET-1 by elastase, and several minor products, paralleled by a loss of its smooth muscle contracting activity. The degradation of ET-1 by PMN microsomes was prevented by DCI, PMSF, or ONO 5046. Our results suggest that an elastase-initiated serine protease cascade is responsible for the sequential conversion of bET to ET-1 by the PMN cytosol. Elastase also partly accounts for the ET-metabolizing properties of PMN microsomes. PMID- 1495980 TI - Quantitative effects of antihydrophobic agents on binding constants and solubilities in water. AB - The effects of urea and of guanidinium chloride on binding constants in water for 6-(4-tert-butylanilino)-naphthalene-2-sulfonate and of bis(p-tert-butylphenyl) phosphate binding to beta-cyclodextrin and to N,N'-bis(6-beta-cyclo dextrinyl)imidazolium ion have been determined. Their effects on the water solubility of p-tert-butylbenzyl alcohol and p-methylbenzyl alcohol have also been examined. Quantitative correlations show that the effects of these additives, which diminish hydrophobic effects, are similar for release of a tert butylphenyl group from a cyclodextrin cavity into water or for solubilizing such a group from a second phase. The effects of these agents on the binding constants for double-ended substrates binding to the bis(cyclodextrin) host are much larger than for a simple substrate binding to monomeric cyclodextrin, consistent with additivity of free-energy perturbations. Ethanol also decreases binding in these systems, and increases solubilities, but the quantitative correlations are less straightforward. PMID- 1495981 TI - Evidence for a Ras-dependent extracellular signal-regulated protein kinase (ERK) cascade. AB - The small GTP-binding protein Ras appears to be required for transformation and differentiation induced by tyrosine kinases. The Ras requirement may be limited to a few tyrosine kinase-regulated signaling pathways or may be universal for all tyrosine kinase actions. Because both Ras and the microtubule-associated protein 2 kinases ERK1 and ERK2 have been implicated in events that lead to neurite outgrowth, we explored the possibility that Ras and ERKs may lie on the same signaling pathway. Utilizing PC-12 rat adrenal pheochromocytoma cell lines that contain a dominant inhibitory Ras mutant (S17N-Ras(H)), we found that Ras was required for stimulation of the ERK cascade by nerve growth factor but apparently not by the heterotrimeric G protein activator AlF4-. Within this cascade, Ras appears to be upstream of an ERK activator, raising the intriguing possibility that Ras may directly regulate a serine/threonine protein kinase. PMID- 1495982 TI - Identification and isolation of the polyferredoxin from Methanobacterium thermoautotrophicum strain delta H. AB - Sequencing the genes encoding the methyl viologen-reducing hydrogenase, cloned from Methanobacterium thermoautotrophicum strain delta H and Methanothermus fervidus, revealed the presence of tightly linked genes, designated mvhB, which were predicted to encode proteins containing six tandemly arranged bacterial ferrodoxin-like domains. A lacZ-mvhB gene fusion has been constructed and expressed in Escherichia coli. Rabbit antibodies raised against the fusion polypeptide purified from E. coli have been used to identify and isolate the polyferrodoxin from Mb. thermoautotrophicum strain delta H. The polyferredoxin accumulates in cells of the methanogen during exponential growth but decreases rapidly on entry into stationary phase. It is not processed into monoferredoxins and is located primarily in the soluble fraction of cell lysates of Mb. thermoautotrophicum. Metronidazole reduction by crude extracts of Mb. thermoautotrophicum strain delta H cells, dependent on the presence of hydrogen and the heterodisulfide CoM-S-S-HTP [formed from the two coenzymes 2 mercaptoethanesulfonic acid (coenzyme M, HS-CoM) and N-(7 mercaptoheptanoyl)threonine O3-phosphate (HS-HTP)], was not inhibited by the antibodies raised against the LacZ-MvhB fusion polypeptide. PMID- 1495983 TI - Meiosis-specific protein selectively associated with sex chromosomes of rat pachytene spermatocytes. AB - During the first meiotic prophase of mammalian spermatogenesis, the sex chromosomes X and Y show a characteristic allocyclic behavior with respect to the autosomes. This is particularly evident during pachytene stage when sex chromosomes form the so-called sex vesicle. This structure is characterized by the condensed state of chromatin, transcriptional inactivity, and the limited extension of chromosome pairing, which is usually restricted to a short segment of sex chromosome axial elements. The molecular basis and functional significance of sex vesicle formation during mammalian spermatogenesis remain obscure. Here we report on the identification of a meiosis-specific sex vesicle protein we called XY40. Immunocytochemical localization on rat testis cryosections with a XY40 specific monoclonal antibody revealed that the labeling is confined to the axial elements of sex chromosomes. Biochemical characterization showed that protein XY40 (40 kDa; pI 5.7-5.8) can be extracted from rat pachytene spermatocytes and recovered in particles of 9.5 S with a native molecular mass of approximately 152 kDa. We speculate that protein XY40 may be involved in the allocyclic behavior of sex chromosomes during male meiotic prophase. PMID- 1495984 TI - Matrix-attachment regions can impart position-independent regulation of a tissue specific gene in transgenic mice. AB - Matrix-attachment regions (MARs) may function as domain boundaries and partition chromosomes into independently regulated units. We have tested whether MAR sequences from the chicken lysozyme locus, the so-called A-elements, can confer position-independent regulation to a whey acidic protein (WAP) transgene in mammary tissue of mice. In the absence of MARs, expression of WAP transgenes was observed in 50% of the lines, and regulation during pregnancy, during lactation, and upon hormonal induction did not mimic that of the endogenous WAP gene and varied with the integration site. In contrast, all 11 lines in which WAP transgenes were juxtaposed to MAR elements showed expression. Accurate position independent hormonal and developmental regulation was seen in four out of the five lines analyzed. These results indicate that MARs can establish independent genetic domains in transgenic mice. PMID- 1495985 TI - Gravitational symmetry breaking in microtubular dissipative structures. AB - Reduction-diffusion theories can account for both morphogenesis and the sensitivity of biological systems to weak fields. They predict that gravity can cause the symmetry breaking that is necessary for pattern formation. Microtubules play an important role in organizing the cell, and recent studies hae shown that they can form in vitro dissipative structures. We have found that these structures show patterns of microtubular orientation that are gravity dependent and that the gravitational field causes symmetry breaking. This behavior, which cannot be explained by convection, is in accordance with the theory of dissipative structures. These results suggest that microtubular dissipative structures may play an important role both in morphogenesis and in accounting for the sensitivity of biological systems to weak fields. They aso provide another explanation for biological gravitropism. PMID- 1495986 TI - Ethidium bromide provides a simple tool for identifying genuine DNA-independent protein associations. AB - DNA-dependent and DNA-independent associations of DNA-binding proteins are important in transcriptional regulation. The analysis of DNA-independent associations frequently relies on assaying protein interaction in the absence of target DNA sequences. We have found that contaminating DNA in protein preparations can stabilize DNA-dependent associations that may appear DNA independent. Three cellular proteins of 70, 85, and 110 kDa coimmunoprecipitated with the octamer motif-binding protein Oct-2 because of the presence of contaminating DNA in the cell extracts. In addition, heterodimer formation between Oct-1 (or Oct-2) and Pit-1 during protein-affinity chromatography was stabilized by the contaminating DNA. In both instances, these DNA-dependent protein associations were selectively inhibited by ethidium bromide in the precipitation reaction without any evident effect on DNA-independent protein associations. Thus, ethidium bromide may serve as a simple and general indicator of DNA-dependent and DNA-independent protein associations. PMID- 1495988 TI - "Rogue" lymphocytes among Ukrainians not exposed to radioactive fall-out from the Chernobyl accident: the possible role of this phenomenon in oncogenesis, teratogenesis, and mutagenesis. AB - Cultured lymphocytes exhibiting extreme cytogenetic damage (rogue cells) were observed in preparations from 8 of 24 individuals sampled in Krasilovka, a Ukrainian village receiving little or no increased radiation after the Chernobyl disaster, but were not observed in an additional 24 persons from two Russian towns in the more contaminated area. This observation cements the worldwide occurrence of these cells. The present data plus a review of the literature establish that rogue cells appear in brief bursts simultaneously in certain individuals of discrete populations. We suggest that the pattern is consistent with the action of a viral trigger that acts directly or indirectly--the latter possibly through the activation of latent chromosomal retroposons. If this phenomenon occurs in other tissues, it may have important implications for oncogenesis, teratogenesis, mutagenesis, and evolution. PMID- 1495987 TI - Genetic and molecular analysis of recessive alleles at the pink-eyed dilution (p) locus of the mouse. AB - Recessive mutant alleles at the pink-eyed dilution (p) locus on mouse chromosome 7 reduce pigmentation of both the coat and eyes. Here we describe the properties and complementation interactions of 10 p alleles, including 6 not previously reported. Several alleles that cause additional phenotypes affecting development, reproduction, and behavior were shown to be deletions by using DNA probes derived from the p region. An alignment of functional and marker-defined units is proposed, giving a linear complementation map that orders at least four functional loci. The characterization of a nested set of deletions around p will facilitate detailed molecular analyses of the genes and developmental functions associated with this part of the mouse genome. PMID- 1495989 TI - Quantitation of immunoglobulin mu-gamma 1 heavy chain switch region recombination by a digestion-circularization polymerase chain reaction method. AB - B lymphocytes expressing surface IgM with or without IgD may switch to the expression of other isotypes (IgG, IgA, or IgE) in the course of immune responses. Analyses of genomic DNA from cloned myelomas and hybridomas have shown that the isotype switch is accompanied by a rearrangement characterized by deletion of DNA between the switch (S) region of the mu gene and that associated with the new isotype, resulting in the formation of a composite S region. Measurement of this deletional rearrangement has been difficult in populations of normal B cells but would be useful for investigating the mechanism of the rearrangement and determining whether deletional rearrangement is responsible for all instances of class switching. We have developed a sensitive assay for deletional rearrangement that we designate the digestion-circularization polymerase chain reaction (PCR). In this assay, genomic DNA is digested with a restriction enzyme that recognizes sites that flank the recombined composite S region. The digested DNA is then ligated at low concentrations to favor the formation of circles. The ligation joins the 5' and 3' ends of each restriction fragment, making it possible to amplify by PCR across the ligated restriction site by using appropriate primers. From DNA that has undergone deletional rearrangement, a single-sized PCR product is produced and can be quantitated. We demonstrate here that the digestion-circularization PCR assay can detect S mu-S gamma 1 rearrangements in B cells cultured with lipopolysaccharide and interleukin 4. The assay is sensitive enough to quantitate switched cells constituting only 1-2% of the population. PMID- 1495990 TI - Importance of growth hormone for the induction of hepatic low density lipoprotein receptors. AB - This investigation was undertaken to determine the possible role of growth hormone (GH) in the hormonal regulation of hepatic low density lipoprotein (LDL) receptor expression. Treatment of normal rats with estrogen (ethynylestradiol, 5 mg/kg per day) increased the number of hepatic LDL receptors, and the LDL receptor mRNA levels were increased 2.4-fold. However, when hypophysectomized rats were treated with estrogen, the hepatic LDL receptor number and the mRNA levels only increased slightly. Treatment with GH was important to restore the induction of hepatic LDL receptors in hypophysectomized estrogen-treated rats. Further, the hypocholesterolemic effect of estrogen was abolished in hypophysectomized rats, and GH reversed this effect. To assess the effect of GH in humans, hepatic LDL receptor binding activity was determined in liver biopsy specimens from gallstone patients pretreated with GH (12 international units/day) prior to operation. GH administration induced hepatic LDL receptors approximately 2-fold, and this was accompanied by a 25% decrease in serum cholesterol. The LDL receptor stimulation caused by GH treatment was of similar magnitude as that observed upon 3 weeks of treatment with an established hypolipidemic drug (pravastatin or simvastatin). The data show that GH has an important role in the regulation of hepatic LDL receptors and suggest that GH secretion may be important for the control of plasma LDL levels in humans. PMID- 1495991 TI - Binding of transition metals by apolipoprotein A-I-containing plasma lipoproteins: inhibition of oxidation of low density lipoproteins. AB - We have found transition metals tightly bound to apolipoprotein A-I-containing lipoproteins [Lp(A-I)] isolated by selected affinity immunosorption from human serum. Prominent among the metal ions detected were iron and copper. By immunoblotting the proteins of Lp(A-I), we detected both transferrin and ceruloplasmin. The transferrin-containing Lp(A-I) particles, isolated by selected affinity immunosorption against transferrin, were larger (mean diameter of 14.2 nm) and had a higher protein content than most high density lipoproteins (HDL). Ultracentrifugally isolated HDL were found to contain much less transferrin, whereas transferrin was found associated with apolipoprotein A-I from the greater than 1.21-g/ml ultracentrifugal fraction. This suggests that the complex is not recovered in the classic HDL density interval because of its very high density. HDL inhibit copper-catalyzed oxidation of low density lipoproteins (LDL) in vitro. We have found that immunoisolated Lp(A-I) are an order of magnitude more effective in inhibiting the oxidation of LDL than ultracentrifugally isolated HDL, on the basis of protein mass. When the Lp(A-I) particles containing transferrin and ceruloplasmin were removed from the bulk of Lp(A-I), inhibition of the in vitro oxidation of LDL was significantly decreased. PMID- 1495992 TI - Increased type 1 plasminogen activator inhibitor gene expression in atherosclerotic human arteries. AB - Decreased fibrinolytic capacity has been suggested to accelerate the process of arterial atherogenesis by facilitating thrombosis and fibrin deposition within developing atherosclerotic lesions. Type 1 plasminogen activator inhibitor (PAI 1) is the primary inhibitor of tissue-type plasminogen activator and has been found to be increased in a number of clinical conditions generally defined as prothrombotic. To investigate the potential role of this inhibitor in atherosclerosis, we examined the expression of PAI-1 mRNA in segments of 11 severely diseased and 5 relatively normal human arteries obtained from 16 different patients undergoing reconstructive surgery for aortic occlusive or aneurysmal disease. Densitometric scanning of RNA (Northern) blot autoradiograms revealed significantly increased levels of PAI-1 mRNA in severely atherosclerotic vessels (mean densitometric value, 1.7 +/- 0.28 SEM) compared with normal or mildly affected arteries (mean densitometric value, 0.63 +/- 0.09 SEM; P less than 0.05). In most instances, the level of PAI-1 mRNA was correlated with the degree of atherosclerosis. Analysis of adjacent tissue sections from the same patients by in situ hybridization demonstrated an abundance of PAI-1 mRNA positive cells within the thickened intima of atherosclerotic arteries, mainly around the base of the plaque. PAI-1 mRNA could also be detected in cells scattered within the necrotic material and in endothelial cells of adventitial vessels. In contrast to these results, PAI-1 mRNA was visualized primarily within luminal endothelial cells of normal-appearing aortic tissue. Our data provide initial evidence for the increased expression of PAI-1 mRNA in severely atherosclerotic human arteries and suggest a role for PAI-1 in the progression of human atherosclerotic disease. PMID- 1495993 TI - Inhibition of thymocyte apoptosis and negative antigenic selection in bcl-2 transgenic mice. AB - The bcl-2 gene, which is overexpressed in human follicular B-cell lymphomas, has been found to extend cellular lifespan through inhibition of apoptosis, or programmed cell death. However, the physiological role of the Bcl-2 protein in lymphocyte development is unclear. We have established a transgenic mouse line that expresses high levels of the Bcl-2 protein in both cortical and medullary thymocytes, disrupting the normal pattern of expression of this gene. We found that in these mice, immature thymocytes became resistant to apoptosis mediated by corticosteroids and calcium ionophores. Untreated thymocytes also exhibited a survival advantage in suspension cultures compared with controls. In addition, overexpression of bcl-2 enabled a proportion of thymocytes and peripheral T cells to escape the process of clonal deletion, which normally eliminates self-reactive T cells during thymocyte maturation. These findings implicate the Bcl-2 protein in regulating the lifespan of maturing thymocytes and in the antigenic-selection process. PMID- 1495994 TI - The budding yeast HRR25 gene product is a casein kinase I isoform. AB - The Saccharomyces cerevisiae HRR25 gene was identified as a regulator of DNA strand-break repair. HRR25 encodes a protein kinase that is closely related to bovine casein kinase I (CKI). CKI is a ubiquitous multipotential protein kinase. Rabbit polyclonal antibodies that recognize and immunoprecipitate Hrr25p have been generated and an immune complex protein kinase assay has been developed. The reaction depends upon HRR25 and shows that Hrr25p uses casein as a substrate. The identity between Hrr25p and bovine CKI suggests that Hrr25p is a yeast isoform of the CKI family and that CKIs may play a role in regulating DNA metabolism. PMID- 1495995 TI - Phycocyanin alpha-subunit phycocyanobilin lyase. AB - Phycobiliproteins, unlike other light-harvesting proteins involved in photosynthesis, bear covalently attached chromophores. The bilin chromophores are attached through thioether bonds to cysteine residues. The cyanobacterium Synechococcus sp. PCC 7002 has eight distinct bilin attachment sites on seven polypeptides, all of which carry the same chromophore, phycocyanobilin. When two genes in the phycocyanin operon of this organism, cpcE and cpcF, are inactivated by insertion, together or separately, the surprising result is elimination of correct bilin attachment at only one site, that on the alpha subunit of phycocyanin. We have overproduced CpcE and CpcF in Escherichia coli. In vitro, these proteins catalyze the attachment of phycocyanobilin to the alpha subunit of apophycocyanin at the appropriate site, alpha-Cys-84, to form the correct adduct. CpcE and CpcF also efficiently catalyze the reverse reaction, in which the bilin from holo-alpha subunit is transferred either to the apo-alpha subunit of the same C-phycocyanin or to the apo-alpha subunit of a heterologous C-phycocyanin. The forward and reverse reactions each require both CpcE and CpcF and are specific for the alpha-Cys-84 position. Phycocyanobilin is the immediate precursor of the protein-bound bilin. PMID- 1495996 TI - Evidence that MutY and MutM combine to prevent mutations by an oxidatively damaged form of guanine in DNA. AB - It has been previously shown both in vivo and in vitro that DNA synthesis past an oxidatively damaged form of guanine, 7,8-dihydro-8-oxoguanine (8-oxoG), can result in the misincorporation of adenine (A) opposite the 8-oxodG. In this study we show that MutY glycosylase is active on a site-specific, oxidatively damaged A/8-oxoG mispair and that it removes the undamaged adenine from this mispair. Strains that lack active MutY protein have elevated rates of G.C----T.A transversions. We find that the mutator phenotype of a mutY strain can be fully complemented by overexpressing MutM protein (Fpg protein) from a plasmid clone. The MutM protein removes 8-oxoG lesions from DNA. In addition, we have isolated a strain with a chromosomal mutation that suppresses the mutY phenotype and found that this suppressor also overexpresses MutM. Finally, a mutY mutM double mutant has a 25- to 75-fold higher mutation rate than either mutator alone. The data strongly suggest that MutY is part of an intricate repair system directed against 8-oxoG lesions in nucleic acids and that the primary function of MutY in vivo is the removal of adenines that are misincorporated opposite 8-oxoG lesions during DNA synthesis. PMID- 1495997 TI - Inhibition of leukemia cell proliferation by receptor-mediated uptake of c-myb antisense oligodeoxynucleotides. AB - Exposure of human leukemia HL-60 cells to an oligodeoxynucleotide complementary to an 18-base sequence (codons 2-7) of c-myb-encoded mRNA has previously been shown to result in inhibition of cell proliferation. Because HL-60 cells express high levels of transferrin receptor we adapted a DNA delivery system based on receptor-mediated endocytosis to introduce myb oligomers complexed with a transferrin-polylysine conjugate into those cells. A DNA.RNA duplex resistant to S1 nuclease digestion was detected as early as 12 hr after culture of HL-60 cells in the presence of the myb antisense/transferrin-polylysine complex. Exposure of HL-60 cells to the myb antisense/transferrin-polylysine complex resulted in rapid and profound inhibition of proliferation and loss of cell viability much more pronounced than that occurring in cells exposed to free myb antisense oligodeoxynucleotides. The transferrin-polylysine/myb sense complex or the transferrin-polylysine conjugate alone had no effect on HL-60 cell proliferation and viability. These findings indicate that myb synthetic oligodeoxynucleotides enter efficiently into HL-60 by transferrin receptor-mediated endocytosis and exert a profound biological effect. Such a delivery system could exploit other ligand-receptor interactions for the selective delivery of oncogene-targeted antisense oligodeoxynucleotides. PMID- 1495998 TI - Similarity of spontaneous germinal and in vitro somatic cell mutation rates in humans: implications for carcinogenesis and for the role of exogenous factors in "spontaneous" germinal mutagenesis. AB - The rate of spontaneous mutation resulting in electrophoretic variants per cell generation in a human lymphoblastoid cell line, on the basis of experiments described in this paper, is found to be 7.2 x 10(-8) per locus. A review of similar data on electrophoretic variants resulting from spontaneous mutation in the human germ line leads to an estimate of 3.3 x 10(-8) per locus per cell generation. It is argued that the similarity of these two estimates, despite an average cell generation time of 18.5 hr for the cultured somatic cells but about 26 days in the germ line, suggests that spontaneous mutation involving nucleotide substitutions is much more dependent on cell generation than on time. This finding permits the inference that environmental (exogenous) variables make a relatively small contribution to the rate of this type of human germinal spontaneous mutation. While in vitro somatic-cell mutation rates, such as derived in this study, provide a basis for modeling the contribution of nucleotide substitutions in multihit/clonal theories of carcinogenesis, it is also argued that the complex of events involved in carcinogenesis, including chromosomal rearrangements and mitotic recombination, could have very different individual probabilities. Estimates for the rates of these other types of mutation are needed to provide a better understanding of the manner in which multiple mutations accumulate in malignant cells. PMID- 1495999 TI - Molecular basis of the membrane-anchored and two soluble isoforms of the human interleukin 5 receptor alpha subunit. AB - By use of a 3' extension PCR strategy, cDNA clones were isolated spanning the transmembrane region and a complete cytoplasmic domain of the human interleukin 5 receptor alpha subunit (hIL5R alpha). These cDNAs differ from previously isolated clones encoding a soluble hIL5R alpha form by a sequence switch at position 1243. When expressed in COS-1 cells, only low-affinity binding of 125I-labeled human interleukin 5 was observed. Coexpression of the hIL5R beta chain led to a 2-fold increase in binding affinity. In addition, this same cloning strategy allowed us to identify a putative second soluble isoform of hIL5R alpha. Genomic data revealed that the two soluble variants arise from either a "normal" splicing event or from the absence of splicing, whereas synthesis of the membrane-anchored form requires alternative splicing. PMID- 1496000 TI - Glutaredoxin homolog encoded by vaccinia virus is a virion-associated enzyme with thioltransferase and dehydroascorbate reductase activities. AB - Glutaredoxins (GRXs), also known as thioltransferases, use glutathione as a cofactor for reduction of disulfides in prokaryotes and eukaryotes. We demonstrate that the vaccinia virus O2L open reading frame encodes a functional GRX, as predicted by Johnson et al. [Johnson, G. P., Goebel, S. J., Perkus, M. E., Davis, S. W., Winslow, J. P. & Paoletti, E. (1991) Virology 181, 378-381] from sequence homology. The 12-kDa protein product of the O2L open reading frame was synthesized after viral DNA replication, coincident with a major increase in cytoplasmic glutathione-dependent thioltransferase activity. The protein was associated with purified vaccinia virions and was not released by treatment with a nonionic detergent unless dithiothreitol was added. The virion-derived protein, as well as a recombinant form expressed in Escherichia coli, exhibited thioltransferase and dehydroascorbate reductase activities indicative of a functional GRX. The postreplicative synthesis of vaccinia virus GRX and its association with virions suggest that the enzyme may have novel roles in the virus growth cycle. PMID- 1496001 TI - Metal substitutions at the diiron sites of hemerythrin and myohemerythrin: contributions of divalent metals to stability of a four-helix bundle protein. AB - A general method is described for substitution of Mn(II) and Co(II) into the diiron sites of hemerythrin and myohemerythrin. Characterizations of these metal substituted proteins show that their structures closely resemble those of the native proteins. In particular, the four-helix bundle structure appears to be maintained. The apomyohemerythrin retains most of the native helix content but is considerably less stable to denaturation than are the metal-containing proteins. The relative affinities of M(II) for apohemerythrin--namely, Co greater than Fe greater than Mn--parallel the stabilities of the M2myohemerythrins to denaturation by guanidinium chloride. These results indicate that for myohemerythrin (i) the majority of the helical structure found in the native protein does not require incorporation of M(II) and (ii) stabilization of the native structure relative to the fully unfolded structure appears to be due predominantly to M(II)-protein interactions, at least for M = Fe and Co. Incorporation of M(II) also generates unfolding cooperativity in myohemerythrin. This cooperativity can be attributed to interhelical interactions, which are prevented in the apoprotein by solvation of the seven metal ligand residues. The results are consistent with a minimal model for folding/unfolding of myohemerythrin and hemerythrin subunits consisting of the sequential equilibria, N in equilibrium with I in equilibrium with D, between native, intermediate, and fully unfolded states, respectively. The properties of apomyohemerythrin make it a candidate for the intermediate state, I. PMID- 1496002 TI - Diversity among tight junctions in rat kidney: glomerular slit diaphragms and endothelial junctions express only one isoform of the tight junction protein ZO 1. AB - ZO-1 is a 225-kDa peripheral membrane protein present in all tight junctions. It was recently shown to consist of two isoforms that differ in the presence of an internal 80-amino acid domain termed motif-alpha. To obtain information on their distribution and potential functional significance we have localized the two isoforms in rat kidney by using antibodies that recognize either both ZO-1 isoforms or the larger, motif-alpha-containing isoform. By immunofluorescence, staining with both antibodies was demonstrated at all tight junctions of tubular epithelial cells and the epithelial cells of Bowman's capsule. In contrast, the motif-alpha-containing isoform was absent from the slit diaphragms of the glomerular epithelium and the tight junctions of glomerular and peritubular capillary endothelial cells. This restricted isoform expression was confirmed by immunoblot analysis comparing proteins from purified glomeruli with those from kidney cortex or medulla. Thus, while both isoforms are expressed in typical epithelial tight junctions, only a single isoform, lacking motif-alpha, is expressed in the highly specialized slit diaphragms, where the intercellular spaces are normally open, and in endothelial junctions, which are readily opened by physiologic signals. The differential expression of ZO-1 isoforms in structurally and functionally distinct junctions in the kidney suggests that they may contribute to defining the variable functional properties, in particular the lability of these intercellular junctions. PMID- 1496003 TI - dOct2, a Drosophila Oct transcription factor that functions in yeast. AB - Oct factors are members of the POU family of transcription factors that are shown to play important roles during development in mammals. Here we report the cDNA cloning and expression of a Drosophila Oct transcription factor. Whole mount in situ hybridization experiments revealed that the spatial expression patterns of this gene during embryonic development have not yet been observed for any other gene. In early embryogenesis, its transcripts are transiently expressed as a wide uniform band from 20% to 40% of the egg length, very similar to that of gap genes. This pattern progressively resolves into a series of narrower stripes followed by expression in 14 stripes. Subsequently, transcripts from this gene are expressed in the central nervous system and the brain. When expressed in the yeast Saccharomyces cerevisiae, this Drosophila factor functions as a strong, octamer-dependent activator of transcription. Our data strongly suggest possible functions for the Oct factor in pattern formation in Drosophila that might transcend the boundaries of genetically defined segmentation genes. PMID- 1496004 TI - A family of erythrocyte binding proteins of malaria parasites. AB - Malaria erythrocyte binding proteins use the Duffy blood group antigen (Plasmodium vivax and Plasmodium knowlesi) and sialic acid (Plasmodium falciparum) on the erythrocyte surface as receptors. We had previously cloned the one P. vivax gene, the one P. falciparum gene, and part of one of the three P. knowlesi genes encoding these erythrocyte binding proteins and described the homology between the P. knowlesi and P. vivax genes. We have completed the cloning and sequencing of the three P. knowlesi genes and identified introns in the P. vivax and P. falciparum genes that correct the previously published deduced amino acid sequences. All have similar structures, with one or two exons encoding the signal sequence and the erythrocyte binding domain, an exon encoding the transmembrane domain, and two exons encoding the cytoplasmic domain with the exception of the P. knowlesi beta gene. The regions of amino acid sequence homology among all the genes are the 5' and 3' cysteine-rich regions of the erythrocyte binding domain. On the basis of gene structure and amino acid homology, we propose that the Duffy binding proteins and the sialic acid binding protein are members of a gene family. The level of conservation (approximately 70%) of the deduced amino acid sequences in the 5' cysteine-rich region between the P. vivax protein and the three P. knowlesi proteins is as great as between the three P. knowlesi proteins themselves; the P. knowlesi beta protein just 3' to this cysteine-rich region is homologous to the P. vivax protein but not to the other P. knowlesi proteins. Conservation of amino acid sequences among these organisms, separated in evolution, may indicate the regions where the adhesin function resides. PMID- 1496005 TI - Disruption of circadian regulation by brain grafts that overexpress Alzheimer beta/A4 amyloid. AB - Alzheimer disease patients exhibit irregularities in the patterns of normally circadian (daily) rhythms. Alzheimer-type pathology has been reported in the hypothalamus and in the suprachiasmatic nuclei, the putative site of the circadian oscillator. We examined the relationship between the neuropathology of Alzheimer disease, as modeled by an animal system, and circadian dysregulation by grafting genetically transformed cells that overexpress beta/A4 amyloid into the suprachiasmatic nuclei of adult rats. Grafts of beta/A4-positive cells, but not of control cells, significantly altered the pattern of activity of implanted rats. Although experimental conditions included light-dark cycles that normally tend to drive rats to 24-h rhythms, animals with grafts of beta/A4-positive cells showed abnormally high levels of activity during the light phase in addition to a disrupted circadian pattern. Periodogram analysis demonstrated significant rhythms outside of a circadian range. The body temperature rhythm of these animals was also weak 6 weeks after grafting; however, unlike activity patterns, body temperature regained a circadian period by 8 weeks after cell implantation. These data indicate that disruption of circadian activity is a behavioral measure of the consequences of beta/A4 accumulation in brain implants. PMID- 1496006 TI - Potentiation of DNA adduct formation in HL-60 cells by combinations of benzene metabolites. AB - Using P1 nuclease enhanced 32P postlabeling, we investigated DNA adduct formation in HL-60 promyelocytic leukemia cells treated with the benzene metabolites hydroquinone, catechol, and 1,2,4-benzenetriol. Comparison of the slopes of the dose-response curves showed that hydroquinone was 7-9 times more effective than 1,2,4,-benzenetriol and catechol at inducing DNA adducts. Comparison of hydroquinone with catechol showed a good correlation between adduct formation and cytotoxicity. Similar comparisons of hydroquinone and 1,2,4,-benzenetriol suggest that cellular processes in addition to DNA adduct formation contributed to cytotoxicity. In cells treated with the combination of hydroquinone and either catechol or 1,2,4,-benzenetriol, DNA adduct formation was 3-6 times greater than the sum of adduct formation produced by single-agent treatments. Treatment with hydroquinone and 1,2,4,-benzenetriol produced DNA adducts not detected after treatment with either metabolite alone. The synergistic interaction of benzene metabolites in the production of DNA adducts may play an important role in the genotoxic effects of benzene in vivo. PMID- 1496007 TI - Relation between the convergence temperatures Th* and Ts* in protein unfolding. AB - A challenge in understanding the thermodynamics of protein unfolding is to explain the 1979 puzzle posed by Privalov. Why do values of the specific enthalpy and specific entropy of unfolding both converge to common values at approximately the same temperature (Th* approximately equal to Ts*) when extrapolated linearly versus temperature? In 1986, a liquid hydrocarbon model gave an explanation for convergence of the specific entropies at Ts*: it happens because the contribution of the hydrophobic effect to the entropy of unfolding goes to zero at Ts*. The reason for convergence of the specific enthalpies at Th* and for the equality Th* approximately equal to Ts* has remained, however, a matter for speculation; recently, some explanations have been given that are based on models for polar interactions in protein folding. We show here that the relation Th* approximately equal to Ts* can be derived straightforwardly without making any assumptions either about polar interactions or about splitting the hydrophobic interaction into two terms--one for the "hydrophobic hydration" and the other for the residual effect, as suggested recently. Thus, the liquid hydrocarbon model explains both halves of Privalov's puzzle. A similar conclusion has been reached independently by A. Doig and D. H. Williams (personal communication). It has been proposed recently that a correction should be made for the relative sizes of a hydrocarbon solute and water when computing the thermodynamic properties of the hydrophobic interaction from a solvent transfer experiment. This correction affects the temperature at which the entropy of transfer equals zero, and it is important to evaluate its effect on the convergence temperature Ts*. We show that making the size correction does not change the conclusion, reached earlier, that the liquid hydrocarbon model explains the convergence of the specific entropies of protein unfolding. PMID- 1496008 TI - Marked reduction of high density lipoprotein cholesterol in mice genetically modified to lack apolipoprotein A-I. AB - Atherosclerosis is a major cause of morbidity and mortality in developed countries. In humans the risk of atherosclerosis is inversely correlated with plasma levels of high density lipoprotein (HDL). As a step in determining whether the experimental reduction of plasma HDL level will increase susceptibility to atherosclerosis, we have used gene targeting in embryonic stem cells to produce mice lacking apolipoprotein A-I, the major protein component of HDL particles. Mice homozygous for the disrupted gene have no plasma apolipoprotein A-I detectable by double immunodiffusion; their total plasma cholesterol and HDL cholesterol levels after overnight fasting are reduced to about one-third and one fifth of normal levels, and they are grossly deficient in alpha-migrating HDL particles. PMID- 1496009 TI - Structural requirements for RNA editing in hepatitis delta virus: evidence for a uridine-to-cytidine editing mechanism. AB - Hepatitis delta virus (HDV) nucleotide 1012 is edited from uridine to cytidine in 10-40% of the RNA genomes during replication. This editing event is an important control point in the HDV life cycle because it results in both the packaging of viral RNA and the inhibition of HDV replication. We find that the editing event is highly specific for both the sequences neighboring nucleotide 1012 and the base-paired context of position 1012 within the unbranched rod structure of HDV RNA. Prior studies identified the base transition at nucleotide 1012 but were unable to distinguish between editing of the genomic versus the antigenomic strands [Luo, G. X., Chao, M., Hsieh, S. Y., Sureau, C., Nishikura, K. & Taylor, J. (1990) J. Virol. 64, 1021-1027]. In this study, comparisons of mutations that differentiate between base pairing in genomic and antigenomic RNAs indicate that the genomic strand of HDV is the actual editing substrate. We conclude that the virus uses a uridine to cytidine editing mechanism, which is provided by the host cell. PMID- 1496010 TI - Structure of a human monoclonal antibody Fab fragment against gp41 of human immunodeficiency virus type 1. AB - The three-dimensional structure of a human monoclonal antibody (Fab), which binds specifically to a major epitope of the transmembrane protein gp41 of the human immunodeficiency virus type 1, has been determined by crystallographic methods to a resolution of 2.7 A. It has been previously determined that this antibody recognizes the epitope SGKLICTTAVPWNAS, belongs to the subclass IgG1 (kappa), and exhibits antibody-dependent cellular cytotoxicity. The quaternary structure of the Fab is in an extended conformation with an elbow bend angle between the constant and variable domains of 175 degrees. Structurally, four of the hypervariable loops can be classified according to previously recognized canonical structures. The third hypervariable loops of the heavy (H3) and light chain (L3) are structurally distinct. Hypervariable loop H3, residues 102H-109H, is unusually extended from the surface. The complementarity-determining region forms a hydrophobic binding pocket that is created primarily from hypervariable loops L3, H3, and H2. PMID- 1496011 TI - The 3' untranslated region of localized maternal messages contains a conserved motif involved in mRNA localization. AB - Messenger RNA (mRNA) localization is emerging as a means of regulating gene expression. This process is operational in fly and frog development, where a subset of maternally inherited RNAs are asymmetrically distributed and thought to impart axial polarity to the embryo. Since most maternal mRNAs are uniformly distributed, an apparatus must exist to recognize and specifically transport these rare localized species. Here I report the identification of a nine nucleotide motif, YUGUUYCUG, common to the 3' untranslated regions of four sequenced messages of this class: Drosophila bicoid and nanos mRNAs and Xenopus An2 and Vg1 mRNAs. To test the role of this nonamer sequence in the localization process, a Drosophila transient assay has been established. The assay reveals that bicoid mRNA specifically lacking this nonamer is partially mislocalized. In contrast, nonamer deletion is inconsequential to message stability. The existence of specific and general mRNA localization signals is proposed and it is suggested that this conserved motif belongs to the latter category. PMID- 1496012 TI - Classical conditioning and protein kinase C activation regulate the same single potassium channel in Hermissenda crassicornis photoreceptors. AB - The patch-clamp technique was used to study the effects of classical conditioning and protein kinase C (PKC) activation on K+ channels of identified neurons in the snail Hermissenda crassicornis. Here we present evidence that classical conditioning and PKC activation similarly modify the same K+ channel. K+ channels were recorded in cells from animals with different training experience. The 64-pS K+ channel appeared with significantly lower frequency in the conditioned group compared to the frequencies in control animals (naive and unpaired). In addition, when present, the 64-pS channel exhibited a lower percentage of open time and an increased interval between opening bursts in cells from conditioned animals. The 42-pS K+ channel was observed with about the same frequency in all three groups, and its percentage of open time was invariant, regardless of the animal's experience. Incubation of the photoreceptor with the PKC activator phorbol 12,13 dibutyrate (PDBu) led to a profound decrease in the percentage of open time of the 64-pS K+ channel, from 35.7% in the control group to 2.5% in the PDBu-treated group. The inactive phorbol 4 alpha-phorbol 12-myristate 13-acetate had no effect. The use of the PKC inhibitor H-7 significantly blocked the phorbol effect. Inside-out patches obtained from phorbol preincubated cells likewise showed the same effect of PDBu on K+ channels, but the effect was not observed when phorbol was added after the cell-free patches were obtained from nontreated cells. By contrast, the percentage of open time of the 42-pS K+ channel remained unchanged after phorbol treatment. PMID- 1496013 TI - Sexual orientation and the size of the anterior commissure in the human brain. AB - The anterior commissure, a fiber tract that is larger in its midsagittal area in women than in men, was examined in 90 postmortem brains from homosexual men, heterosexual men, and heterosexual women. The midsagittal plane of the anterior commissure in homosexual men was 18% larger than in heterosexual women and 34% larger than in heterosexual men. This anatomical difference, which correlates with gender and sexual orientation, may, in part, underlie differences in cognitive function and cerebral lateralization among homosexual men, heterosexual men, and heterosexual women. Moreover, this finding of a difference in a structure not known to be related to reproductive functions supports the hypothesis that factors operating early in development differentiate sexually dimorphic structures and functions of the brain, including the anterior commissure and sexual orientation, in a global fashion. PMID- 1496014 TI - Conformation for a beta-cyclodextrin monosubstituted with a cyclic dipeptide. AB - The structural characterization of a beta-cyclodextrin monosubstituted with the peptide cyclo(L-His-L-Leu) is reported. This work provides an x-ray example of a covalently bound group that folds in such a way that the terminal apolar side chain is retained in the hydrophobic interior of the cone-shaped cyclodextrin cavity. 6-Deoxy-6-cyclo(L-histidyl-L-leucyl)-beta-cyclodextrin crystallizes in the space group P1 with cell dimensions a = 14.728(8) A, b = 15.084(7) A, c = 18.182(10) A, alpha = 94.36(6) degrees, beta = 95.81(5) degrees, gamma = 116.08(9) degrees; overall isotropic agreement R = 10.6% for 5703 observed reflections (Fo greater than 3 sigma). The molecular structure consists of two independent molecules with the formula C54H86N4O36.7.25H2O. Each molecule assumes a "sleeping swan"-like overall shape with the hydrophobic leucine side chain inserted inside the cavity of the macrocycle. The two independent units give rise to a head-to-tail dimer linked by hydrogen bonds occurring between primary and secondary hydroxyl groups of the two monomers. The packing of the dimers produces cavities containing water molecules. There are infinite hydrophilic channels running in the crystal, which is similar to what is found in the structures of cyclic peptides. PMID- 1496016 TI - Distinct processes mediate glycoprotein and glycopeptide export from the endoplasmic reticulum in Saccharomyces cerevisiae. AB - Protein and peptide export from the Saccharomyces cerevisiae endoplasmic reticulum was examined in vitro using the secretory protein pro-alpha-factor and a synthetic tripeptide containing the acceptor site for N-linked glycosylation as substrates. The release of both glycosylated pro-alpha-factor and glycotripeptide from the endoplasmic reticulum was dependent on cytosol, temperature, and ATP. Antibodies against two proteins essential for the formation of transport vesicles, Sec23p and p105, inhibited glyco-pro-alpha-factor exit from the endoplasmic reticulum but did not affect the release of the glycosylated tripeptide. Furthermore, in contrast to pro-alpha-factor, the exported glycopeptide was not associated with a membrane fraction and did not acquire Golgi-specific alpha(1-6)-linked mannose residues. We conclude that the glycosylated tripeptide leaves the yeast endoplasmic reticulum by a route different from the secretory pathway, possibly through an ATP-driven pump. PMID- 1496015 TI - Dynamic NMR spectral analysis and protein folding: identification of a highly populated folding intermediate of rat intestinal fatty acid-binding protein by 19F NMR. AB - The folding of intestinal fatty-acid binding protein has been monitored by 19F NMR after incorporation of 6-fluorotryptophan into the protein. The two resonances resulting from the two tryptophans of this protein showed different dependencies on denaturant concentration. One of the resonances was in slow chemical exchange between two resonance frequencies, native and completely unfolded. The changes for this resonance occurred over a denaturant concentration range identical to that monitored by circular dichroism or fluorescence during unfolding. The other resonance continued to show changes at concentrations of denaturant well above that needed to complete the unfolding transition as monitored by optical techniques. Site directed mutagenesis showed that tryptophan 82 was the residue responsible for the unexpected behavior. We conclude, based on complete line-shape analysis, that there are significant concentrations of one or more intermediates in equilibrium with the native and unfolded forms. The structure of the intermediate(s) is more similar to the completely unfolded form of the protein than to the native structure, since little if any secondary structure is present. Further, these structure(s) persist at high denaturant concentrations and may represent local initiating sites in the folding of this beta-sheet protein. PMID- 1496017 TI - Steroid 21-hydroxylase deficiency: three additional mutated alleles and establishment of phenotype-genotype relationships of common mutations. AB - Lesions in the gene encoding steroid 21-hydroxylase [steroid hydrogen-donor: oxygen oxidoreductase (21-hydroxylating), EC 1.14.99.10] result in defective adrenal steroid synthesis; the severe forms are known as congenital adrenal hyperplasia. To facilitate complete characterization of mutations in this region of tandemly repeated genes, we have developed selective PCR amplification and direct sequencing of full-length nonpseudogene steroid 21-hydroxylase genes. This technique identifies known mutations, characterizes or excludes unknown mutations, and determines the gene-copy number. Three additional defective alleles were found. A Gly-292----Ser mutation and a frameshift mutation at Arg 484 (GG----C) were identified in patients with severe steroid 21-hydroxylase deficiency. An allele with three additional sequence variations--C----T at 4 bases upstream of translation initiation, Pro-106----Leu, and Pro-454----Ser- were identified in two siblings with late-onset deficiency. Pro-454 is conserved in four species, indicating its importance for normal enzyme function. Functional consequences of individual alleles have been determined in vivo by studying individuals with only one steroid 21-hydroxylase gene. Detailed analyses of clinical data revealed that genotyping could predict the clinical course of the disease. The locations of disease-causing mutations on different haplotypes of the steroid 21-hydroxylase gene region are described. PMID- 1496018 TI - Brefeldin A affects early events but does not affect late events along the exocytic pathway in pancreatic acinar cells. AB - Brefeldin A (BFA) blocks protein export from the endoplasmic reticulum (ER) to Golgi complex and causes dismantling of the Golgi complex with relocation of resident Golgi proteins to the ER in some cultured cells. It is not known whether later steps in the secretory process are affected. We previously have shown that in BFA-treated rat pancreatic lobules, there is no detectable relocation of Golgi proteins to the ER and, although Golgi cisternae are rapidly dismantled, clusters of small smooth vesicles consisting of both bona fide Golgi remnants and associated vesicular carriers persist even with prolonged BFA exposure. We now report the effects of BFA on transport of proteins through the secretory pathway in exocrine pancreatic cells; we pulse-labeled pancreatic lobules with [35S]methionine and then chased for various times before adding BFA. When BFA was added at pulse, treated lobules released less than 10% of radioactive protein in comparison with controls, regardless of whether or not the lobule cultures were stimulated with carbamoylcholine. However, when lobules were pulsed and then chased for 30, 45, or 60 min before BFA addition, the amount of labeled protein released was comparable in both BFA-treated and untreated cultures. Furthermore, the kinetics and amounts of basal and carbamoylcholine-stimulated release of unlabeled alpha-amylase from storage in zymogen granules were similar in both control and BFA-treated lobules. Therefore, in the rat pancreas, BFA blocks ER to Golgi transport but does not affect later stages along the secretory pathway, including intra-Golgi transport, exit from the Golgi complex, formation and concentration of secretory granules, and exocytosis. PMID- 1496019 TI - Phorbol ester-induced amino-terminal phosphorylation of human JUN but not JUNB regulates transcriptional activation. AB - Phorbol ester tumor promoters activate gene transcription by regulating both the synthesis and posttranslational modification of the activator protein 1 (AP-1) transcription factor, c-Jun and JunB are components of the mammalian AP-1 complex. Here we demonstrate that in U-937 human leukemic cells, phorbol esters stimulate the phosphorylation of the amino terminus of human c-Jun (JUN) but not human JunB (JUNB). Mutational analysis indicates that serine-63 and -73, which reside within the putative regulatory domain of JUN, are required for both constitutive and phorbol 12-myristate 13-acetate-inducible N-terminal JUN phosphorylation. To determine the functional role of this N-terminal phosphorylation, we prepared several chimeric proteins containing the N-terminal 84 amino acids (positions 5-89) of human JUN or murine JUNB fused to the yeast GAL4 DNA-binding domain. This region was found to be sufficient for the phorbol ester-inducible transcriptional activity of JUN, but not JUNB. This induction was abolished by the mutation of serine-63 and -73 to leucine residues. Thus, we propose that phorbol esters enhance the trans-activation potential of JUN, but not JUNB, by the phosphorylation of the N-terminal regulatory domain of JUN. PMID- 1496020 TI - Delineation of putative mechanisms involved in antibody-mediated clearance of rabies virus from the central nervous system. AB - The in vitro biological activities of several rabies virus-neutralizing monoclonal antibodies (mAbs) were compared with their ability to prevent a lethal rabies virus encephalomyelitis. The protective activity of a particular mAb in vivo did not correlate with its virus-neutralizing activity in vitro; rather it was related to the mAb's ability to inhibit virus spread from cell to cell and to restrict rabies virus RNA transcription. Since treatment of rabies virus-infected cells with virus-neutralizing mAbs results in an endocytosis of the antibody, we hypothesize that an antibody may exert its inhibitory activity even after uptake by the cell. Post-exposure treatment of rats with a mAb that inhibited both virus spread and virus RNA transcription in vitro resulted in viral clearance from the central nervous system and protected the animals against a lethal rabies virus infection. PMID- 1496021 TI - Synthetic neural modeling applied to a real-world artifact. AB - We describe the general design, operating principles, and performance of a neurally organized, multiply adaptive device (NOMAD) under control of a nervous system simulated in a computer. The complete system, Darwin IV, is the latest in a series of models based on the theory of neuronal group selection, which postulates that adaptive behavior is the result of selection in somatic time among synaptic populations. The simulated brain of Darwin IV includes visual and motor areas that are connected with NOMAD by telemetry. Under suitable conditions, Darwin IV can be trained to track a light moving in a random path. After such training, it can approach colored blocks and collect them to a home position. Following a series of contacts with such blocks, value signals received through a "snout" that senses conductivity allow it to sort these blocks on the basis of differences in color associated with differences in their conductivity. Darwin IV represents a new approach to synthetic neural modeling (SNM), a technique in which large-scale computer simulations are employed to analyze the interactions among the nervous system, the phenotype, and the environment of a designed organism as behavior develops. Darwin IV retains the advantages of SNM while avoiding the difficulties and pitfalls of attempting to simulate a rich environment in addition to a brain. PMID- 1496023 TI - Recommended terminology for venous thrombosis. PMID- 1496022 TI - Activation of p70s6k is associated with phosphorylation of four clustered sites displaying Ser/Thr-Pro motifs. AB - Partial amino acid sequences were obtained from 22 internal tryptic peptides of rat liver p70s6k (M(r) 70,000 ribosomal protein S6 kinase), 3 of which were found to contain phosphorylated residues. To determine whether these sites were associated with p70s6k activation, the kinase was labeled to high specific activity with 32P(i) in Swiss mouse 3T3 cells. By sequential cleavage with CNBr and endoproteinase Lys-C followed by two-dimensional tryptic peptide analysis, it could be shown that all of the sites were located in a small endoproteinase Lys-C peptide of M(r) 2400. Analysis of the p70s6k protein sequence revealed a single candidate that could represent this peptide. Three tryptic peptides derived from the endoproteinase Lys-C fragment were chosen by a newly described computer program as the most likely candidates to contain the in vivo sites of phosphorylation. Synthetic peptides based on these sequences were phosphorylated either chemically or enzymatically and found to comigrate by two-dimensional thin layer electrophoresis/chromatography with the four major in vivo labeled tryptic phosphopeptides. Three of the phosphorylation sites in these peptides were equivalent to those sequenced in the rat liver p70s6k. In addition, all four sites display the motif Ser/Thr-Pro, typical of cell cycle-regulated sites, and are clustered in a putative autoinhibitory domain of the enzyme. PMID- 1496024 TI - [Ultrastructural characteristics of the venous endothelium in primary varices of the legs]. AB - The author establishes by using TEM a considerable variability of endothelial cell ultrastructure in primary varicose veins. Endothelial cells of varicose veins differ from these in normal ones by deformation of configuration of the cells and of their nucleus accompanied by alterations in other cellular organelles. These changes express the stimulation of the endothelial cell aiming their adaptation to hemodynamic changes ABD combine with destructive intracellular changes as well. Probably, adaptation capacities of endothelial cells are restricted to definite limits in which they can change themselves. Beyond these limits endothelial cells can not compensate and undergo degenerative alterations. The author discusses the possible functional changes of the venous endothelium related to substance transport in the venous wall, to lipid accumulation in the endothelium and to thrombus formation. PMID- 1496025 TI - [Does heat therapy still have a role in phlebology?]. PMID- 1496026 TI - [Clinical criteria of chronic severe venous insufficiency]. PMID- 1496027 TI - [Surgical treatment of post-thrombotic cellulitis. A new method]. AB - The author suggests an original and novel method for the surgical treatment of post-thrombotic hypodermatitis, which involves, in association with the elimination of all long reflux vessels, the incision of the skin along the healthy edge of hypodermatitis. This is followed, after the elimination of short reflux vessels from the sub-fascial compartment, by the taking of pieces of sub fascial aponeurosis which ensure drainage of the hypodermis. After one year, 7 of 12 patients were apparently totally cured. After 2 years, only 2 patients still had slight signs of hypodermatitis. At the present time, patients are followed up with elastic compression of moderate intensity. PMID- 1496028 TI - [Parvovarice, a new compression method]. PMID- 1496029 TI - [Venous pain, 30 years after the 1st International Congress of Phlebology in Chambery]. AB - In 1960, the first International Conference of Phlebology, organised at Chambery by Jean Marmasse under the egis of R. Tournay included only three subjects in its programme, one of which was: "venous pain". What is the status of venous pain thirty years on? Can we compare our current concepts with work from past years? Have we advanced in knowledge and in its clinical and therapeutic applications? All these questions are even more worthy of consideration bearing in mind world wide increased interest in Phlebology and its even richer future. The Chambery Conference established a clear pattern with: two basic reports: "pain due to essential varicose veins and to trophic disorders" (C. Huriez, F. Desmons, M. Thoreux) and "pain in phlebitis" (R. Fontaine); three analytical and differential reports "pain due to interlinked arterial and venous disorders" (F. Piulachs), "pain in the lower limbs due to interlinked gynecological and venous disorders" (A. Bret, R. Legros) and "pain due to the association of osteoarticular and rheumatic disorders or of neuralgia in venous disease patients" (J. Forestier); and nine other studies, the following being worthy of particular attention: a very interesting report by R. Tournay: "Pain in venous disorders of the lower limbs related to their treatment"; and two papers: "pain of "cellulite" type and the metameric disposition of the lower limbs in relation to functional disorders of the ovary" (S. Bourgeois), and "exercise pain and rest pain in varicose vein sufferers" (J. Marmasse); three German reports (F. Jaeger, F. Maid-Fischer and D. Gross) on the pathogenesis and mechanisms of venous pain; and the report of M. Comel "epiesthesia and histoangeological correlations". Since that time, venous pain has no longer figured in the same format on the programme of any international conference, nor at meetings of the French Society of Phlebology. Progress has thus occurred insidiously... Mention may be made of the following with regard to essential varicose veins: some progress in knowledge of cramps, phlebalgia and venous paresthesiae; attribution to venous syndromes of "restless legs", which have been such a source of intrigue for the past hundred years, and interest in inflammatory pain of the superficial venous system and of subcutaneous cellular tissue in relation with venous insufficiency, as well as ulcer pain. However, it is in the area of acute deep venous thrombosis that everything has been disrupted. Firstly, with the established certainty that the clinical picture leads to errors in more than 50 p. cent of cases, both by excess and default.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1496030 TI - [The relation between venous stasis and the occurrence of pain]. AB - Venous stasis is a situation encountered commonly in varicose disorders. The potential implications of this decrease in oxygen levels in terms of the status of the cells of the vein were assessed. When endothelial cells are subjected to hypoxia, there is stimulation of the cells which shows itself as increased synthesis of prostaglandins and of PAF (Platelet Activating Factor). The synthesis of these typical mediators of inflammation results from activation by the calcium of phospholipase A2 which releases the arachidonic acid of phospholipids and this increase in intracellular calcium results itself from a fall in efficacy of calcium pumps due to the fall in ATP caused by hypoxia. Thus the fall in oxygen leads to the production of mediators of inflammation which activate leucocytes and result in local micro-inflammation which can be very rapidly eliminated if the circulation is restored but which can also cause irreversible damage to the vein by changes in venous tissue due to activated leucocytes which release proteases and free radicals after having penetrated the intima of the vein. These processes offer an explanation for the histological changes seen in varicose veins and the onset of localised pain during the development of such disease. PMID- 1496031 TI - [Inflammation and subcutaneous calcification of venous origins]. AB - There have been few descriptions up to now of calcifications in chronic venous insufficiency, other than in cases where venous insufficiency is complicated be severe trophic disorders and in particular ulcers. It was therefore felt to be of interest to assess the presence of calcifications in venous insufficiency without trophic disorders. This study was based upon 40 cases recruited in the phlebology out-patient clinic of the Notre Dame de Bon Secours Hospital. Calcifications of the lower limbs were found in 7 patients, either by palpation, routine X-rays or ultrasonography. The etiopathogenic mechanisms of this occurrence not having been elucidated, a number of hypotheses are put forward on the basis of acquired data concerning: the process of formation of ectopic calcifications, changes in subcutaneous tissue, the ultimate consequences of venous stasis and of raised venous pressure, due essentially to anoxia and inflammation. One hypothesis can thus be put forward: that of inflammation. The release of cells and mediators of inflammation, the production of free radicals, causing damage to the cells of connective tissue and to the organic framework (collagen fibres) and changes in the chemical environment could combine to result in the formation of calcifications in subcutaneous tissue. However, inflammation has not been proven to be the primary etiological factor. PMID- 1496032 TI - [Painful manifestations of the sequelae of phlebitis]. AB - Pain may be absent from the various manifestations making up a post-phlebitis syndrome but when it is present it varies considerably from one patient to another. Thus the very common feeling of heaviness, generally not painful, may be perceived as being painful by certain patients either because of the particular severity of the feeling or because of a low pain threshold in certain cases. Since no method for the objective measurement of pain exists, the assessment of this symptom and of its severity remains highly subjective, most often based upon statements by the patients. However, in practice a distinction can be drawn between the following: Pain related to venous stasis: a simple feeling of heaviness most often but which, in certain patients, may take on a painful connotation. Among such "stasis" pains, particular mention must be made of venous intermittent claudication, a progressive feeling of calf tension during walking which becomes increasingly painful and finally forces the sufferer to stop. This symptom is generally linked to the obstruction of a large collecting vein. Pain accompanying a leg ulcer usually results from secondary infection. Mention may be made of the role of inflammatory lesions developing around the trophic problem and which may encompass nerves, in particular the internal saphenous nerve. Although classical, causalgia type pain is certainly rarer. Demyelinisation of peripheral nerves has been suggested as being at its origin. Once again, the role of inflammatory processes linked to secondary infection appears to be notable. The treatment of pain in a post-phlebitis patient must take the greatest possible account of the pathophysiology of the post-phlebitis syndrome responsible: disinfection of a leg ulcer, treatment of venous stasis by elastic support, or by surgery or sclerosing injections. Sympathectomy has been suggested in causalgia type pain. In fact, this operation has scarcely any indications in post-phlebitis syndrome. PMID- 1496033 TI - [Pain in venous thrombosis of the leg]. AB - According to D. Reinharez, pain and edema are the commonest presenting symptoms in phlebology. Pain is one of the most classical symptoms of an ordinary deep venous thrombosis, a valuable feature when present, in the form of deep tension, heaviness, swelling and a feeling of dead weight. It is often absent or slight. It may consist merely of a dull cramp, or of an "undefinable" (C. Bourde) odd, heavy leg. It generally affects the calf but may involve the sole of the foot, the heel, the thigh, the groin or even the true pelvis. This feeling, although "imprecise and variable" (P. Wallois, P. Griton) is highly suggestive. It increases on standing and walking in the form of unilateral uncomfortable tension, heaviness or painful swelling, which maybe a source of worry or even anxiety to the patient. Tenderness on palpation of venous tracts and their stretching is more suggestive. In the opinion of M. Duruble, Neuhof's sign (feeling of tender fullness of the calf) is more reliable than Homans' sign (pain in the calf caused by passive dorsiflexion of the foot, with the lower limb in extension) which essentially stretches only the posterior tibial venous system. The value of Sigg's sign (pain in the popliteal fossa on passive extension of the knee) is controversial. Far more rare is phlegmasia coerulea dolens or Gregoire's blue leg, complicating phlegmasia alba dolens or of sudden onset, with initial very severe or even "intolerable" pain (J.J. Pinot) in Scarpa's triangle, rapidly spreading to the limb. In varicose phlebitis (M. Perrin) or superficial thrombophlebitis or varico-phlebitis (A.A. Ramelet) or superficial venitis (J.P. Henriet), pain most often consists of moderate burning tension overlying the thrombosed vein(s), increased by palpation and mobilisation. Sometimes severe initially, it is exacerbated by the slightest touch. In total, pain, regardless of its characteristics, its site and/or its severity, is one of the most constant clinical features of venous thrombosis. It is a warning sign for the clinician and should lead to emergency request for non-invasive investigations (Doppler Echo) which will enable confirmation or elimination of the diagnosis. PMID- 1496034 TI - [Painful hypertonia of the calves. The role of the level of arousal apropos of 25 new cases]. AB - Role of the level of alertness. Based upon 25 new cases. The author, after referring to the leg muscle bed syndrome associated with exercise, reports the frequency of painful spasticity of the calves, occurring initially at rest and in particular at night in the form of a restless legs syndrome, then secondarily during the day with varying degrees of persistence at rest and during exercise. This problem frequently has a lateral dominance and appears to be induced by self maintained functional muscular spasticity of the gastrocnemii and soleus, explained by a study. It is frequently attributed to a venous etiology. This study based upon 25 cases enabled definition of the diagnosis and showed the probable links between EMG hyperactivity and a high level of alertness indicative of a predisposing situation. PMID- 1496035 TI - [Clinical characteristics of pain in chronic venous insufficiency]. AB - Since the report of the 1st International Conference of Phlebology at Chambery, devoted to venous pain, the subject has scarcely attracted attention apart from the meeting of the Benelux Society of Phlebology devoted to "pain in the legs". Pain due to superficial venous insufficiency has scarcely changed in nature for 30 years and remains one of the major presenting symptoms in phlebology. Acute or chronic, punctate or diffuse, modifications in this functional symptomatology have been accentuated, or have varied in their aspects under the influence of certain fashions or certain habits of modern life, i.e.: sedentary behaviour, underfloor heating, the use of oral contraceptives or of menopausal hormone replacement therapy. However, the distribution of the various aspects of venous pain remains in the same proportions as those described by the authors cited previously. While the etiological diagnosis must essentially eliminate all other causes: arterial, neurological, muscular, articular, it is essential not to neglect deep venous insufficiency of the gemellar veins, often responsible for a wide range of symptomatology and still all too often neglected. The pathogenesis of this pain not only involves the concept of pain receptors but also the appearance of algogenic metabolites at the site of the microcirculatory unit, to which endothelial cells are particularly sensitive during stasis. In fact, pain is the expression of disorders concerning local exchanges, whether thermal, pressure, metabolic or hemorheological. It is the alarm bell of venous insufficiency and merits the attention of the phebologist who must thus undertake active treatment before problems become irreversible. PMID- 1496036 TI - [Interpeak components of event-related potentials--comparison between normal and schizophrenic groups]. AB - Event-related potentials (ERPs) during a two-tone discrimination task were recorded in 85 normal subjects and 110 schizophrenic subjects. We divided ERPs into 4 interpeak components. We named them A, A', B and B'. A is the component from the stimulus point to n100 peak. A' is the one from n100 peak to p200 peak. B is the one from p200 peak to n200 peak. B' is the one from n200 peak to p300 peak. Their latency was named Al, A'l, Bl, and B'l respectively. Their amplitude was also named Aa, A'a, Ba and B'a respectively. Bl and A'l of the schizophrenic group were both significantly longer than those of the normal group. B'a of the schizophrenic group was significantly smaller than that of the normal group. Interrelations between interpeak components of the normal group were examined statistically. Regarding latency, a significant negative correlation was seen between Al and A'l, and also between Bl and B'l. Regarding amplitude, a significant positive one was seen between Aa and A'a, and also between Ba and B'a. Interrelations between Al and A'l, Bl and B'l, Aa and A'a, and Ba and B'a of the schizophrenic group were the same as those of the normal group. These negative correlations in latency suggest that n100 peaks and n200 peaks have 'jitter'. A combination of interpeak components is supposed to reflect a higher function of the brain. There was a significant negative correlation between (A + A')l and (B + B')l in the normal group, but there was not a significant one between them in the schizophrenic group. The schizophrenic group is supposed to have a certain abnormality in a higher function of the brain. Our result suggests that we may possibly be able to associate an abnormal focus around p200 peak with some symptoms and signs of schizophrenia. PMID- 1496037 TI - [A clinical study on the therapeutic significance of classifying total amnesia]. AB - Eight cases of total amnesia were reported. In common to all the cases, there were the definite histories of characteristic situations charged with depressive and isolated mood, although their modes of social adjustment appeared relatively good respectively. Four of the eight cases presented the clinical course of total amnesia as Yamada et al. had previously pointed out. The other four developed total amnesia in peculiar progress and presented rather involved clinical courses. Examining the clinical courses and psychodynamics, the author has suggested that total amnesia would be able to classify two types, such as "simple course type" and "unstable course type". The important difference between two types is as follows. "Simple course type": There were pressing situations after series of actual pending problems such as debts, troubles with a lover and mismanagement in business. Onset of them were reactive under these environmental situations. They presented calm and stable features during partial amnestic period. As the family relations and the actual environments were improved better, they recalled more parts of their personal histories without any difficulty. "Unstable course type": In these cases, the intrapsychic weakness were more important factors than the actual environmental problems. Unlike "simple course type", whenever they recalled some parts of their personal histories, they presented unstable fluctuating features with confusion. Therefore, they needed intensive therapeutic intervention and concern. Generally speaking, total amnesia can be considered not only as defense for the actual conflicts with a repression mechanism but also as "psychologic suicide" which Abeles et al. have mentioned. In addition, emotionally confused evolution in this type may be regarded as exposure of the intrapsychic weakness itself. By the way, the close relationship between total amnesia and suicide has been mentioned in some papers. In this type of total amnesia, attempted suicides were actually seen. So the author has stressed that the risk of suicide should be impressed in the treatment of total amnesia. Among the previously reported cases of total amnesia, in which the clinical courses can be read, 27 cases are "simple course type" and 22 cases are "unstable course type" according to the author's knowledge. And the number of total amnesia has been increasing with the times. So in future, total amnesia may increase in number. The author has emphasized the therapeutic significance of classifying total amnesia. It is useful for the treatment of total amnesia to recognize "unstable course type", in order to foresee the unstable clinical course.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1496038 TI - [The efficacy of day care in preventing the readmission of chronic schizophrenic patients]. AB - Prolongation of outpatient treatment period assessed on the basis of outpatient survival rate (SR), etc., was used to evaluate the efficacy of day care (DC) in preventing the readmission of 95 chronic schizophrenic patients with a history of multiple admissions. Before using DC, SR gradually decreased as time since discharge passed, and after 300 weeks had fallen to 26%. After the introduction of DC, on the other hand, although SR decreased up to 230 weeks, from 230 weeks SR is found to plateau so that by 300 weeks it was 51%. In other words, not only was a lower readmission rate observed at the end of 300 weeks after the introduction of DC than before, but it became clear that about 230 weeks (approximately 4.5 years) had become a turning point with respect to prognosis. In addition, the mean duration of outpatient treatment was significantly longer beginning 175 weeks after discharge, after the introduction of DC than before (at 175 weeks, p less than 0.05; at 200 weeks, p less than 0.01, Wilcoxon test). The above demonstrate a readmission preventing effect and an outpatient treatment period prolonging effect of DC. Next, whole 95 patients were divided into a response group and a no-response group depending on whether their outpatient treatment period had been prolonged by DC. The prescribed doses of psychotropic drugs, which were represented by equivalent doses of chlorpromazine and haloperidol, were compared during the outpatient treatment period before and after the introduction of DC in the subjects in the response group, however, at least the possibility that increasing doses of psychotropic drugs as maintenance therapy agents was involved in prolonging the outpatient treatment period was ruled out. Moreover, the 47 patients who were readmitted within 300 weeks after the introduction of DC were divided into a response group and a no-response group, and when the proportions of patients who had to be readmitted during DC were compared, there were more in the no-response group (p less than 0.05, chi 2 test). Many of the cases requiring readmission during DC were intractable, and since there were many such patients in the no-response group, it appeared that the likelihood of belonging to the no-response group meant the simultaneous likelihood of being intractable during DC. Furthermore, when we checked the percentage of the number of DC users among patients who came to the outpatient clinic without being admitted, it was found to plateau at 30% around 170 weeks after discharge.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1496039 TI - [Some examination and requests for "principles of the mental health care" submitted by the United Nations Commissions on Human Rights]. AB - I do appreciate the "PRINCIPLES FOR THE PROTECTION OF PERSONS WITH MENTAL ILLNESS AND FOR THE IMPROVEMENT OF MENTAL HEALTH CARE" dated 5 February 1991 submitted by the Commission on Human Rights. To make it even more explicit, however, the following paragraphs should be added to two of the Principles: 1. As for Principle 11. 13, the requirement of informed consent by a personal representative should be prescribed in the case of a major medical or surgical procedure for an incompetent patient, in addition to the approval by an independent review body concerning such therapy, for the sake of consistency with Principle 11. 7 with regard to the right of privacy. 2. As for Principle 11. 15, the following three paragraphs should or may be added which have also been prescribed in "Principles for the Human Experiments" by the Japanese Society of Psychiatry and Neurology (1973), for the sake of consistency with Principle 11.7 with regard to the right of privacy and Principle 11.4 providing for the special protection of an incompetent patient: 2. 1 The requirement of informed consent by his/her personal representative should be prescribed in a case of clinical trials or experimental treatment for an incompetent patient. 2. 2 Intrusive and irreversible clinical trials and experimental treatment should never be carried out on a patient who is an involuntary patient in a mental health facility and they may be carried out on any other patient only where an independent external body has satisfied itself that there is genuine informed consent of the patient. 2. 3 It may be better to add the following paragraph: "clinical trials and experimental treatment shall never be carried out on an incompetent patient which are not necessary for the therapy of his/her disease or which are possible on a normal healthy person or a mentally ill patient having the ability to give informed consent." PMID- 1496040 TI - [The present state of mental health services in the Tohoku district. II. Some changes after the enforcement of the Mental Health Act]. PMID- 1496041 TI - [Emergencies in child clinical practice? The question of therapeutic analytic consultations]. AB - The author analyses three analytically oriented interviews of a ten year old girl who presented a severe school phobia. These interpretation-oriented consultations helped to partly untangle the intricacies between fantasy life, childhood history and some present events in family life. Thus the symptoms could recede immediately after the consultations. Through this both frequent and illustrative case report, the author discusses the metapsychological and technical aspects concerning the legitimacy and relevance of therapeutic analytically-oriented consultations. This consultation modality can avoid the massive increase of the symptoms and of the attached secondary benefits. It enables us to take into account a certain amount of emergency in child clinical practice. PMID- 1496042 TI - [A guide for the evaluation of adult-infant dialogue (GEDAN)]. AB - The guide presented in this article has evolved on the basis of the observation of early interactions, at two different levels: microanalytic, on one hand, and macrodescriptive, on the other hand. The sample included 48 dyads from 16 clinical and non-clinical families. Elaborated within a systems approach, this guide considers both the dyadic unit and the individual contributions of the partners; likewise it includes subjective as well as objective data. The procedure involves distinct steps and results in the diagnosis of interaction according to three modes: consensual, conflictual and paradoxical. The instrument itself, the data concerning its validation through microanalysis as well as the instructions are described for the trained observer-reader. PMID- 1496043 TI - [Some questions for Egle and Moses Laufer]. PMID- 1496044 TI - [Sexual abuse of underage children: incest and extra-familial abuse]. AB - After defining the concept of sexual abuse and its limitations, the author demonstrates how the confrontation with sexual abuse may provoke counter transferential movements in staff members and spoil the quality of help programs. The author then outlines the pathogenesis of the concept and describes clinical signs, acute or chronic, presented by the abused child. He then discusses the diagnostic process according to diverse disclosure situations (by the child him/herself, parent-witness, etc.). Reliability of the revelations are then discussed. Two important parts of this paper deal with intervention methods: first, the crisis intervention, focused on collecting information, support to the suffering persons, active protection of the child and possible collaboration with judiciary authorities; cure intervention: social help to the family, speech groups, role of punishment, etc. PMID- 1496045 TI - [Reflections on the notion of the "central masturbation fantasy" of adolescence]. PMID- 1496046 TI - [Psychic trauma in catastrophes. Views and reviews]. AB - A review of literature on the subject reveals a great diversity of views but can nevertheless serve as a guideline for concrete interventions. A recent survey of the psychological state of the traumatised armenian population serves as a background for the theorisation of the trauma. Under the shock, the splitting of the ego and of the primitive self leads to a contradictory symptomatology. The ego level is mainly caracterised by repetition whereas the reactivation of the primitive self leads to avoidance of contact. Confusional states result from the gap between these two instances. Priority is given to group therapy when the ego fails to play its part. When the ego is reestablished, but must face certain losses, among which the loss of its own continuity, individual therapy is at place. Understanding the psychic trauma leads to a model of change. PMID- 1496047 TI - [Radiating masturbation fantasy]. PMID- 1496048 TI - [Psychoanalysis of adolescents: some reflections based on the works of E. and M. Laufer]. PMID- 1496049 TI - [The role of microrhythms and macrorhythms in the emergence of thought in the infant]. AB - Cathexis of time and even more of waiting is considered critical for the development of thought, as S. Freud himself often pointed out. The author discusses the means available to the infant for growing out of the hallucinatory perceptual system and coming to a representational activity which implies a capacity to tolerate the frustration provoked by the waiting. Two distinct interactive processes play a role in the appearance of thought: on one part the macrorythms of repetition involving the interaction partners, mainly in their care-giving activities; on the other part the microrythms with their discontinued rhythms, unsatisfied waiting involving the partners in short sequences, mainly in play activities. The author tentatively demonstrates on the basis of clinical examples and various sources that these seemingly opposed moments give a structure to a unique element of the dyad: the interactive rythm. Rythm is a condition of the capacity to wait and thus of the capacity to think. PMID- 1496050 TI - [The central masturbation fantasy]. PMID- 1496051 TI - [In pursuit of an object]. AB - The author proposes an extension of the transitional phenomenon concept. Beginning with Winnicott's well known description, the author reviews the successive transformations of transitional space, first materialized and then increasingly "intrapsychic" and which persists in the individual all life long in various forms. Transformations go from the gross blanket to a more figurative little bear, then to play activities, creative drawing of the child, and finally to hypotheses and theories. This progressive hold on the object involves the mediation of transitional space--first found then created--and is instrumented through age-specific different means: concrete handling; certain characteristics of baby-talk such as voice intonation, use of the past tense before playing and the conditional in playing; redundancies, parentheses and abstractions. In the course of this paper, the author gives his personal view on the subtle differences between figuration and representation, and on the relationship between abstraction and aesthetical feeling. PMID- 1496052 TI - Multivantaged assessment of depression in schizophrenia. AB - While it is recognized that depression frequently can occur together with fundamental symptoms of schizophrenia, estimates of the prevalence of schizophrenia-related depression have been very variable. This variability may be due in part to the difficulty in clearly separating depressive symptoms from negative symptoms. A more valid method of assessing depression might combine evaluations from multiple vantage points. This study, which involved 26 hospitalized schizophrenic patients, tested the proposition that complete assessment of depression requires three separate sources of input: self-rating (subjective mood state), clinician rating (affective state), and observer rating (behavioral manifestations). In the present study, patients were evaluated on self-rating instruments for mood states, clinician-rated scales including the Hamilton Rating Scale for Depression, and observer-rated scales. These vantage points, though overlapping in some respects, were found to provide independent information on the experience of depression in schizophrenia. Clinician-rated and observer-rated assessments tended to correlate significantly, while self-rated subjective reports were discordant, thus complementing the assessments from the other two vantage points. PMID- 1496053 TI - Subsyndromes in chronic schizophrenia: do their psychopathological characteristics correspond to cerebral alterations? AB - This article examines the relationship between psychopathological subsyndromes in schizophrenia and cerebral alterations. A factor analysis of the psychopathological characteristics of 50 DSM-III schizophrenic patients revealed four subsyndromes. On the basis of these subsyndromes, four corresponding clusters of patients--remitted, chronic delusional, chronic asthenic, and chronic disorganized--were identified. These clusters were then compared with respect to negative symptoms, treatment response, neurological soft signs (NSS), and computed tomographic findings, such as the ventricle-brain ratio (VBR), using a discriminant analysis. The first discriminant function consisted of negative symptoms and significantly differentiated the remitted cluster from the three chronic clusters. Within the chronic clusters, the disorganized cluster was clearly identified by the second discriminant function (VBR and NSS). The third function (width of the interhemispheric fissure) provided only a tentative differentiation between the chronic delusional cluster and the chronic asthenic cluster. Although the subsyndromes of chronic schizophrenia share negative symptoms as a common feature, they appear to differ somewhat with regard to their morphological sites. These findings indicate that negative symptoms may arise from different psychopathological states and corroborate the existence of three subsyndromes in chronic schizophrenia. PMID- 1496054 TI - Disruption of social circadian rhythms in major depression: a preliminary report. AB - While dysregulations of physiological circadian rhythms are common findings in depression and have been posited to be involved in the mediation of depressive episodes, only recently has the role of social circadian rhythms in the pathogenesis of depression been a focus of interest. The Social Rhythm Metric (SRM), designed to describe the regularity of a human subject's social circadian rhythms, was used in this study to compare the social rhythms of depressed patients with those of normal controls and to determine the relationship between SRM scores and depression severity. Depressed patients' SRM scores were significantly lower than those of normal controls. The SRM negatively correlated with scores on the Hamilton Rating Scale for Depression. Overall social activity was negatively correlated with a Hamilton item, social activity impairment. The results of this preliminary study support the hypothesis that social zeitgebers are disrupted in major depression. PMID- 1496055 TI - Facial emotion discrimination: I. Task construction and behavioral findings in normal subjects. AB - Facial discrimination tasks (age, happy-neutral, and sad-neutral) were developed to address the need for activation tasks that engage emotional processing and can be used during physiologic neuroimaging ("neurobehavioral probes"). The stimuli pictured professional actors and actresses who had been screened for asymmetric features. In experiment I, same-sex stimuli were used to examine the performance of normal subjects (24 men, 15 women) on the three tasks. Performance was better during the emotion-discrimination tasks than during the age-discrimination task, and males had higher sensitivity scores for the detection of sad emotion. However, experiment II showed that the sex of the stimulus interacts with the sex of the subject. Compared with female subjects, male subjects (n = 10) were selectively less sensitive to sad emotion in female faces. Female subjects (n = 10) were more sensitive overall to emotional expression in male faces than in female faces. Thus, men and women differed in performance depending on the sex of the facial stimulus. PMID- 1496057 TI - Facial emotion discrimination: III. Behavioral findings in schizophrenia. AB - Emotional discrimination was studied in patients with schizophrenia (n = 20) and matched controls. Performance of the emotion-discrimination tasks in the schizophrenic patients was impaired, relative to their performance of an age discrimination task. Performance patterns in the patient group could also be reliably distinguished from those of normal controls. The impairment was associated with the severity of both emotional and nonemotional symptoms specific to schizophrenia, but not with the severity of nonspecific symptoms. The deficit associated with schizophrenia is more marked than that reported for depression (Gur et al., 1992), particularly for the emotion-discrimination tasks, and showed no difference between "happy" discrimination and "sad" discrimination. The main difficulty in patients with schizophrenia is the assignment of emotional valence to neutral faces. The magnitude of the deficit underscores the salience of emotional impairment in schizophrenia, and its relation to cognitive dysfunction in this disorder merits further scrutiny. PMID- 1496056 TI - Facial emotion discrimination: II. Behavioral findings in depression. AB - The facial discrimination tasks described in part I (Erwin et al., 1992) were administered to a sample of 14 patients with depression and 14 normal controls matched for sex (12 women, 2 men) and balanced for age and sociodemographic characteristics. Patients performed more poorly on measures of sensitivity for happy discrimination and specificity for sad discrimination, and had a higher negative bias across tasks. Severity of negative affect was correlated with poorer performance for patients. The results suggest that depression is associated with an impaired ability to recognize facial displays of emotion. PMID- 1496058 TI - Obsessive-compulsive characteristics in patients with idiopathic spasmodic torticollis. AB - To explore suggested relationships between involuntary motor disorders and obsessive-compulsive disorder (OCD), we evaluated obsessive-compulsive characteristics in patients with idiopathic spasmodic torticollis (IST). Twenty two patients with IST had significantly higher scores than 29 age- and sex matched healthy controls on the Yale-Brown Obsessive-Compulsive Scale and the obsessionality subscale of the Symptom Checklist-90-Revised. The IST patients also had higher (though not significantly so) scores on the Maudsley Obsessive Compulsive Inventory. Their Beck Depression Inventory scores were likewise higher than those of controls. These results provide additional support for the theory of a link between basal ganglia disorders and psychiatric disorders. PMID- 1496059 TI - Neurocognitive impairment in dramatic personalities: histrionic, narcissistic, borderline, and antisocial disorders. AB - Thirty-seven patients with personalities in the dramatic cluster (DSM-III-R histrionic, narcissistic, borderline, and antisocial) and 40 controls matched for age and gender were evaluated on 16 neurocognitive variables. The evaluation screened for deficits in functions of attention, memory, language, abstraction, and behavior planning/sequencing. Analysis of variance revealed significant deficits in neurocognitive performance among patients with dramatic personalities, particularly in subtests requiring multi-step, multi-element associative operations. PMID- 1496060 TI - Borna disease virus: possible causal agent in psychiatric and neurological disorders in two families. PMID- 1496061 TI - Introduction: D. W. Winnicott's cultural space. PMID- 1496062 TI - Religious thinking as transitional conceptualization. PMID- 1496063 TI - Loss and creativity: notes on Winnicott and nineteenth-century American poets. PMID- 1496064 TI - Recycling. PMID- 1496065 TI - Knowledge in transition: toward a Winnicottian epistemology. PMID- 1496066 TI - The fetish, transitional objects, and illusion. PMID- 1496067 TI - Conductor or director? Transitional space in psychotherapy and in the theater. PMID- 1496068 TI - The fire that never goes out. PMID- 1496069 TI - A psychoanalytic weltanschauung. PMID- 1496070 TI - Psychologists' views of a patient's religiousness. AB - 500 psychologists were mailed clinical vignettes and a questionnaire regarding a prospective patient seeking to adopt a child. The vignettes were equivalent except for a paragraph stating the patient's religious beliefs. Analysis showed that neither statements of religiousness nor stability of belief was shown to influence the clinicians' judgements on whether adoption should occur, the probability that they would recommend therapy, or estimate of the patient's adaptive functioning. Psychologists with 13 to 19 years of experience were more likely to recommend therapy than more or less experienced groups, although this finding was not related to religiousness. PMID- 1496071 TI - Use of direct coping resources in dealing with jealousy. AB - The relationship between combined person and relational variables and use of direct coping behaviors was investigated among 185 undergraduates who currently had dating partners. Individuals with high scores on these sets of variables used significantly more direct coping behaviors than did those with low or intermediate scores. PMID- 1496072 TI - Drug use among university undergraduate students. AB - A sample of 457 undergraduate university students were surveyed to assess their current use of illicit drugs. Such information is to be used as a baseline to examine the effectiveness of drug prevention programs designed for this population. Marijuana was the most common illicit drug used among these students, and men were significantly more likely to report use. Age differences were noted; older students (age greater than or equal to 22 yr.) were more likely to report drug use than those students under 22 years of age. The age differences suggest that there may be a shift away from drug use among the younger students. The low over-all rate of drug use may make difficult the evaluation of prevention programs. PMID- 1496073 TI - Positive associations between anticipatory anxiety and needle pain for subjective but not for physiological measures of anxiety. AB - So far, the association between anxiety and pain has not been studied with measures tapping a physiological dimension of anxiety. Therefore, during a blood extraction procedure, we recorded subjective anxiety, electrodermal activity, heart rate, and intensity of pain. Subjects were 15 patients with panic disorder and 24 healthy subjects. Positive associations between subjective anxiety and pain were found in each group. The physiological activity preceding the venipuncture, however, was not significantly related to the intensity of the pain. PMID- 1496074 TI - Changes in learning-style preferences: a reply to Ruble and Stout. AB - This note is a reply to Ruble and Stout's 1992 critique of our 1991 study of changes in learning style over time. While some of their comments have merit, the remaining conclusions are that the dimension scores on the Learning Styles Inventory exhibit considerable stability over time and should be analyzed when assessing changes in learning style. PMID- 1496075 TI - Effects of group membership on perception of risk for AIDS. AB - The role of social identity as a moderator for perception of risk for AIDS has not been examined. The purpose of this study was to examine perception of risk for AIDS as a function of membership in an identified risk group. 34 subjects who were homosexual, 58 intravenous drug users (IV), and 34 college students rated a 21-item list of behaviors for perception of AIDS risk. The findings indicate that the IV drug-use group significantly underestimated five risk behaviors, four of which are high probability behaviors of IV drug-users and two of which are exclusively IV drug-use behaviors. The homosexual group significantly underestimated four risk behaviors, all of which are primarily characteristic of that group. The college group was generally more accurate in assessing risk than either of the other two groups. These findings support the hypothesis that membership in a perceived risk group is related to differential perceptual bias associated with the need for positive social identity for one's group. PMID- 1496076 TI - Hostility and guilt among Native American students. AB - Buss and Durkee's Hostility-Guilt Inventory was given to 23 white and 23 Native American college students. The Native American subjects scored significantly higher on the Resentment Hostility subscale while the white students scored higher on the Indirect Hostility and Guilt subscales. Implications for research are discussed. PMID- 1496077 TI - Effects of type of instruction on solution of psychological self-help problems. AB - Information in self-help books is typically presented in one of three formats: didactic information, examples, or practice problems. The present study examined the effects of information format on the solution of personal problems. Four test problems were given to 200 subjects recruited from introductory psychology classes. Each of ten groups received a different type of information immediately prior to solving each test problem. Three of the groups received information in Didactic (D), Example (E), and Practice Problem (P) formats, respectively, while a control group received no information (NI). Six other groups (DD, DE, DP, EE, EP, and PP) received combinations of two sets of information prior to each test problem. The letters that designate each of these groups represent the formats in which the two sets of information were presented. A Ryan-Einot-Gabriel-Welsch multiple-range analysis indicated that groups EE, DP, EP, and DE obtained significantly higher scores than NI. Examples were effective as instructional material when presented with other information and when presented in pairs. Practice problems were effective when combined with other types of information but not when presented with other practice problems. PMID- 1496078 TI - Self-defeating behavior, depression, and suicidal preoccupation. AB - Scores on a measure of self-defeating personality were associated with depression and suicidal preoccupation in a sample of 58 college students. PMID- 1496079 TI - Antecedents of narcissism and psychological reactance as indicated by college students' retrospective reports of their parents' behaviors. AB - 49 men and 120 women responded to the Narcissism Personality Inventory, the Hong Psychological Reactance Scale, and a questionnaire regarding parental practices. Men reported that their fathers used spanking more heavily than did women, while women reported more than did men that their mothers provided encouragement toward independence. As compared to mothers on these reports, fathers were less likely to be described as "fair," to use praise, money as rewards, or "grounding," and to have interest in their children's activities, but more likely to be described as "strict." Men (but not women) reported that their fathers had been more likely to administer spankings than were their mothers. Persons who were more narcissistic tended to score higher in reactance and had fathers who used monetary rewards more and encouraged independence to a greater extent. These results are contrary to those expected from Kernberg's and Kohut's views linking narcissism to less nurturance by parents. Higher psychological reactance scores correlated with less praise, more scolding, and more verbal abuse from both parents. Psychological reactance scores also correlated with more spanking by fathers and with their being described as being less fair. These results suggest that punitive disciplinary styles are not related to narcissism but are to psychological reactance. PMID- 1496080 TI - Unemployment and suicide in Northern Ireland. AB - For Northern Ireland, yearly mean percentages of unemployment and suicide rates (per 100,000 population) for specific age groups and by sex were compared over a 19-year period. Significant results were obtained for only two age groups of males (15-24 yr. and 45-54 yr.) and none for females. PMID- 1496081 TI - Attitudes towards health, health behaviour, and personality factors among school students very high on empathy. AB - It was hypothesized that school students very high on empathy would have better self-esteem, behave in a healthier manner, and also have more positive attitudes towards health behaviour than the least empathetic ones. Students were from a comprehensive school, from gymnasium, and from vocational school (Ns = 4268, 2205 girls, 2063 boys, aged 14 to 20 yr.). A modified Mehrabian and Epstein Empathy Scale and the Sensitivity scale were given. The Battle Self-esteem Scale, Form AD measured self-esteem and the Osborn and Harris Scale assertiveness. As a narcissism measure we used the modified Emmons Narcissism Scale. Scores were divided into quartiles. The most empathetic students were compared with the least empathetic ones; the former were more assertive, less narcissistic, less self focussed, and more sensitive. They had more positive attitudes towards health behaviour: they smoked less and used less alcohol than the least empathetic ones. A holistic empathetic trend is seen in thoughts and in behaviour, which works against narcissism. These results confirm that humans need education on empathy in schools to promote mental growth and health behaviour. PMID- 1496083 TI - Predicting behavior of high and low self-monitors: an application of the theory of planned behavior. AB - Using Ajzen's theory of planned behavior, behavior intentions, attitudes, subjective norms, and perceived behavioral control were assessed for 24 high and for 29 low self-monitors. In addition, behavior (attendance at class lectures) was unobtrusively recorded. Intentions were best predicted by attitudes of the low and by subjective norms of the high self-monitoring groups. Low self monitors' overt behavior was predicted by intentions, and high self-monitors' behavior by the interaction of intention x perceived behavioral control. PMID- 1496082 TI - Psychosocial characteristics of persons convicted of driving while intoxicated. AB - Psychosocial and sociodemographic characteristics were obtained on a sample of 498 Missouri DWI offenders. The information included problems associated with alcohol use, past treatment, arrest data, stressful life events, depression, and substance abuse. Descriptive results are discussed in terms of theoretical and practical implications. PMID- 1496084 TI - A comparison of mental health of multiple sclerosis patients with silver/mercury dental fillings and those with fillings removed. AB - In this study was compared the mental health status of 47 multiple sclerosis patients with silver/mercury tooth fillings (amalgams) to that of 50 patients with their fillings removed. On the Beck Depression Inventory the multiple sclerosis subjects with amalgams suffered significantly more depression while their scores on the State-Trait Anger Expression Inventory indicated the former group also exhibited significantly more anger. On the SCL-90 Revised, subjects with amalgam fillings had significantly more symptoms of depression, hostility, psychotism, and were more obsessive-compulsive than the patients with such fillings removed. On a questionnaire containing 18 mental health symptoms multiple sclerosis subjects with amalgam fillings reported a history of 43% more symptoms than those without amalgam fillings over the past 12 months. These data suggested that the poorer mental health status exhibited by multiple sclerosis subjects with dental amalgam fillings may be associated with mercury toxicity from the amalgam. PMID- 1496085 TI - Jenkins Type A scores in the relation of stress and premenstrual symptoms. AB - To evaluate the manner in which the Type A scores are associated with the relationship between stress and premenstrual symptoms, 102 college women were administered the College Life Experiences Survey, the Jenkins Activity Survey, and the Premenstrual Assessment Form. An hierarchical regression analysis supported the direct effects hypothesis and indicated that the Type A scores are associated with more reported menstrual symptoms at all levels of stress. PMID- 1496086 TI - Factor analysis of the Rudie-McGaughran Essential-Reactive questionnaire for VA alcoholic men. AB - In this study factor analysis was used to estimate the validity of the Rudie McGaughran Essential-Reactive questionnaire. Answers of VA alcoholic men were tape-recorded and scored using the Rudie and McGaughran criteria. Only 2 factors, economic dependence and gastrointestinal symptoms, were validated using factor analysis. Five of the remaining six factors evaluated dimensions of dependence unique to the Essential alcoholic men. PMID- 1496088 TI - Hiring practices in dental education: comparison of top-and lower-ranked schools. AB - The ten top-ranked dental schools, as indicated in The Gourman Report, had hired significantly more faculty members from among their own graduates (Mdn=42.5%) than had ten randomly selected lower-ranked dental schools (Mdn=19.6%). However, the proportions of faculty members hired by the ten top-ranked dental schools from graduates of the top-ranked schools other than their own (Mdn=15.9%) were nearly identical to the proportions of faculty members hired by the lower-ranked schools from graduates of the ten top-ranked schools (Mdn=17.2%). Both top-ranked and lower-ranked schools showed wide variations in their tendencies to hire faculty from top-ranked schools. Some variables that might account for these variations in hiring practices are noted. PMID- 1496087 TI - Alcohol effects on behavioral thermoregulation with microwave radiation. AB - Ethanol may play an active role in modifying "set point" levels in conjunction with behavioral thermoregulation. A geometric series of doses of ethanol solutions was administered (ip) prior to fixed-interval 2-min. schedules of microwave reinforcement in rats tested in a cold environment. Four Sprague-Dawley rats were conditioned to regulate their thermal environment with 5-sec. exposures of MW reinforcement. Friedman's nonparametric test showed significant differences between ethanol doses, and Sign tests showed that moderate and high doses of ethanol suppressed operant behavior reinforced by MW radiation. Interactions between changes in "set-point" and discriminative properties of ethanol are discussed. PMID- 1496089 TI - Attitudes of teenagers who know someone with AIDS. AB - 68 students who reported knowing a person with AIDS were matched with 68 students who did not know anyone with AIDS. Those who knew a person with AIDS showed less anxiety about interacting with someone with AIDS. PMID- 1496090 TI - Multidimensional health locus of control as partial predictor of serum phosphorus in chronic hemodialysis. AB - The Multidimensional Health Locus of Control Scale was administered to 137 chronic hemodialysis outpatients in a survey designed to examine the relationship of these scores to serum phosphorus, a laboratory indicator of dietary compliance in end-stage renal disease. In a multiple regression analysis, scores on the Powerful Others Locus of Control subscale accounted for 8.9% of the variance in serum phosphorus. Discussion includes a tentative explanation of the findings and limitations of the design. PMID- 1496091 TI - Exploration of the relationship between choral singing and successful aging. AB - This paper describes a retirement village community chorus of 49 with the goal of understanding the place of choral activities in the lives of these older people. Group musical activity provides a link to previous satisfying experiences and serves as a preventive measure against alienation. However, the nature of the activity may be consistent with a willingness to give up some inner directedness. Additional research is recommended since the present design with a comparison group of 49 non-choral members did not allow separation of effects of selection from those of activity. PMID- 1496092 TI - Locus of control orientation of obese adolescent girls and children of alcoholics in outpatient treatment. AB - Obese adolescents and children of alcoholics have been reported to exhibit an external locus of control orientation. Due to the perceived loss of control over personal eating behavior versus limited control over environmental circumstances, it was believed that obese adolescent girls would show greater externality than children of alcoholics. Rotter's I-E Scale was administered to 19 moderately obese adolescent girls and 10 girls who were children of alcoholics in outpatient treatment. While both groups scored within the external range of control orientation, there was no statistically significant difference between the samples. Contrary to prediction, obese adolescent girls and adolescents from alcoholic environments have similar world views on control orientation. PMID- 1496093 TI - Combat and social support as variables in perceived symptomatology of combat related posttraumatic stress disorder. AB - This study used an analog approach to the perceptions of tour of duty, combat and noncombat, and levels of social support, high and low. Their influence was assessed in the symptomatology of Posttraumatic Stress Disorder. 80 subjects were randomly assigned to read one of four vignettes depicting levels of combat and social support as main effects. Results were congruent with recent research indicating significant main effects for combat and social support in the symptomatology of Posttraumatic Stress Disorder. PMID- 1496094 TI - Validity of the 16 PF-E experimental norms for adults with mental retardation. AB - Validity of the Sixteen Personality Factor Questionnaire Form E (16 PF-E) experimental norms for adults with mental retardation was evaluated by comparing 16 PF-E responses of mentally retarded adults with staff ratings. Three primary scales (i.e., A, C, and G) received tenuous support. No support was found for the remaining 13 primary scales. PMID- 1496095 TI - Effects of age on ranking for reduction in work force. AB - A laboratory experiment tested the hypothesis that age and written descriptions of performance affected simulated evaluations for reduction in work force. 56 supervisors and managers attending night school reviewed written descriptions of seven individuals' performance. Seven different ages ranging from 25 to 63 years were paired with each individual's performance in a within-subject Latin square design. Each subject rated seven simulated individuals on 10 attributes and made recommendations in the form of comparative rankings for a simulated reduction in force. Chronological age effects on performance rankings were not found. Statistically removing rating components (work performance and sociability) from rankings using an analysis of covariance also yielded no age-related bias but did indicate that the subjects were able to distinguish among performance descriptions. These findings are discussed in relation to the Age Discrimination in Employment Act. PMID- 1496096 TI - Additional evidence on age-related differences in Machiavellianism in an adult sample. PMID- 1496097 TI - Effects of purpose of appraisal on discriminability and accuracy of ratings. AB - Here we evaluate, replicate, and extend 1982 research by Zedeck and Cascio on the relationship between purpose and characteristics of rating. We propose and test an alternative explanation for the Zedeck and Cascio conclusion that discriminability in ratings is affected by their purpose. Results provide partial support for both explanations. Using a measure of rating accuracy as the criterion, no significant effect of purpose is obtained. PMID- 1496098 TI - A graduate seminar on problems in professional psychology. PMID- 1496099 TI - Interpersonal behavior and the structure of dreaming. AB - A three-dimensional model of adult dreaming styles shows a close correspondence with other models representing frameworks of waking experience and interpersonal behavior. These close parallels support the ubiquity of the factors identified by Robert F. Bales in his integrative new field theory and may help to bring the study of dream function more clearly into the realm of personality and social psychology. PMID- 1496100 TI - Reliability and validity of the Adolescent Family Life Satisfaction Index. AB - The purpose of this study was to develop and evaluate the Adolescent Family Life Satisfaction Index. The self-report questionnaire was tested for internal consistency reliability. Tests for construct validity, concurrent validity, and internal consistency reliability provided support for the use of the over-all Adolescent Family Life Satisfaction Index, Parental Subscale, and Sibling Subscale for the measurement of adolescents' reports of satisfaction with family life. PMID- 1496101 TI - Affective control efficacy and cognitive control efficacy: a comment. PMID- 1496102 TI - [Clinical aspects of the consequences of the Chernobyl AES accident]. PMID- 1496103 TI - [An attempt at a polythetic classification of a group of clean up team workers after the Chernobyl AES accident]. AB - Using the complex statistics methods with due regard for the time lapsed from the moment of exposure to ionizing radiation, multifactors of the accident and the number of studies, the manifestations of the radiation effect (within the dose range from 0.1 to 0.5 Gy) on certain functional systems in a group of Chernobyl A.P.S. accident liquidators. PMID- 1496104 TI - [Determination of autoantibodies to antigens of thymic epithelial cells of clean up team workers and patients who survived acute radiation sickness at distant periods after irradiation]. AB - A group of patients, suffering from sequelae of acute radiation sickness (ARS), and liquidators was studied 5 years after exposure to a complex of factors resulting from the Chernobyl A.P.S. disaster. Studied were: the antibody titres to antigens of the cytoplasm of thymus epithelial reticulum cells and to Hassall's corpuscles the levels of serum immunoglobulins M, G, A; and the content of serum alpha 1-thymosin. Patients with ARS sequelae and liquidators showed a high level and incidence of autoantibodies to antigens of cytoplasm of thymus epithelial reticulum cells and to Hassall's corpuscles. There were no significant differences between the antibody levels in the blood of patients with ARS sequelae and liquidators. The antibodies were found to belong to IgM class; there was a correlation between the serum IgM titres and the rate of the indirect immunofluorescence reaction with autoantibodies to antigens of the cytoplasm of the thymus epithelial reticulum cells. To identify autoantibodies cryostat sections of human and mouse, (CBA x C57BL/6) F1, thymus as well as the epithelial and stromal cell culture of mouse thymus can equally be used. PMID- 1496105 TI - [Several indices of the peripheral immune system in clean up team workers and patients who survived acute radiation disease 5 years after effects of the radiation accident factors]. AB - A group of liquidators and patients survived acute radiation sickness (ARS) was studied five years after the effect of radiation factors resulted from the Chernobyl A.P.S. disaster. Studied were the number of T-lymphocytes (SD2+, SD3+, SD5+), subpopulations SD16+ and SD25+, the content of SD16+ and SD25+ lymphocytes and B-cells, as well as the levels of serum IgM, A, G; determined was the concentration of serum alpha 1-thymosin. A decrease was noted in the number of T cells of the examined patients, with respect to all markers studied: the number of SD4+ cells was found decreased in patients with ARS sequelae and normal in liquidators. The decrease in serum alpha 1-thymosin was a function of dose. Dynamics of changes in the T-cells of the examinees may reflect the new trends in the radiation response of T-lymphocytes which were not directly related to initial damages to the latter. The injury to the stroma of the thymus and especially to its epithelial cells may be the basis for later postirradiation damages to the immune system. The decrease in the concentration of alpha 1 thymosin in the blood serum of the examinee is the manifestation of the thymus hypofunction. In liquidators and patients with the ARS sequelae the number of SD25+ cells increased markedly indicating the existence of the source of endogenous cell activation. The content of B-lymphocytes in all studied groups of patients was reduced which may serve as a criterion of chronic stress. PMID- 1496106 TI - [Radionuclide transfer by migratory birds]. AB - Evaluation of the zoogenic transfer of radionuclides from the 30-km zone around the Chernobyl NPP was necessary because of the enormous heavily polluted territory and mighty flow of migratory birds who tended to large rivers, the Dnieper and Pripyat. The integral estimate of the transferred amount was obtained as a product of three variables: the transfer factor (0.0077 m2/kg for 137Cs; 0.0107 m2/kg for 90Sr), the density of birds (0.002 kg/m2, at the mass of migrants about 5000 t per year), and the total fund of radionuclides throughout the territory. The upper estimated limit of the annual transfer rate was 5.5 Ci (2E + 11 Bq) for 137 Cs and 1.8 Ci (6.7E + 10 Bq) for 90 Sr. Restrictions of hunting are recommended within the northern part of the Kiev reservoir. PMID- 1496107 TI - [Features of pine seedling growth under the effects of radiation]. AB - The growth of Pinus sylvestris seedlings was delayed and polystem occurrence increased with chronic irradiation (a cumulative dose of external gamma-radiation was 6-8 Gy in 1986 and 0.7 Gy in 1990). The apical meristem activity was inhibited and central stem and main root died off under the effect of the radiation doses applied resulting in the development of plants of a specific floating form. PMID- 1496108 TI - [Comparative radiation sensitivity of monkeys, Macaca rhesus and Macaca fascicularis]. PMID- 1496109 TI - [Osmotic homeostasis and radiosensitivity of NKLy lymphosarcoma cells]. AB - In experiments with cells of ascites NKLy lymphoma differing in ploidy and position in the cell cycle, a study was made of the radiosensitivity, osmotic homeostasis peculiarities and thermoradiation changes in potassium content. It was shown that the resistance of osmotic homeostasis of NKLy cells to thermoradiation correlated with their radioresistance and was maximally displayed in cells at the stage of DNA synthesis. PMID- 1496110 TI - [Concept of the effect of low doses of ionizing radiation on cells and its possible use in the interpretation of medical-biological consequences]. AB - A concept is proposed where the events induced by low doses of ionizing radiation with low linear energy transfer have different script than those induced by high doses. Its essence consist in the existence of a small fraction (subpopulation) in clonal heterogeneous population whose cells are determined for a specific programmed response induced by a number of action that are potentially able (at high doses) to decrease the survival of the given population. The function of the postulated cell is a deliberate sacrifice necessary for formation of evolutionary reserve. A mechanism of this response is based on an autogeneration of wide-scale genome rearrangements in cells and is not connected with direct influence of genetically hazardous agents on DNA. This leads to arising of a number of genetic variants (evolutionary reserve cells). Selection among them enhancing survival of the population may in the same time lead to harmful consequences for the organism (if there are malfunctions of the immune system). Medical-biological consequences of the effect of low doses are associated with the appearance of such clones and biologically active products secreted from the exposed cells. Mechanisms responsible for the above phenomena are discussed. PMID- 1496111 TI - [Changes in the activity of 5'-nucleotidase and protein kinase of the hepatic plasma membrane depending on the dose rate in x-ray irradiation of rats]. AB - In studying the effect of X-irradiation of rats with a dose of 4 Gy at different dose rates (96 and 4.6 cGy/min) the authors have revealed an increase in 5' nucleotidase activity at a high dose rate (the first 24 h following irradiation) and a decrease in protein-kinase activity at a low dose rate (on days 3 and 7). The preinjection of alpha-tocopherol prevents the changes observed. PMID- 1496112 TI - [Effects of gamma irradiation on biosynthesis of nuclear matrix proteins of the liver in pregnant rats and their embryos]. AB - A study was made of the incorporation of 35S-methionine into nuclear matrix proteins of hepatic cells of pregnant rats and their embryos subjected to single gamma-irradiation (60Co, 1 and 2 Gy, 0.0233 Gy/s) on days 3, 13 and 17 of pregnancy and embryogenesis. On day 21 of pregnancy and embryogenesis a decrease in the rate of incorporation of 35S-methionine into nuclear matrix proteins was shown to be a function of radiation dose and time of pregnancy and embryogenesis on the moment of exposure. PMID- 1496113 TI - [Activity of antioxidant system enzymes and lipid peroxidation product content in the liver and thymus of rats in the early stages of irradiation]. AB - The activity of enzymes of the antioxidation system and the content of some lipid peroxidation products in the liver and thymus of irradiated (0.21 C/kg) rats have been investigated. Glutathione reductase and glutathione transferase activity in the liver and thymus of rats decreased during the first 24 h after irradiation. There was a phase change in the catalase activity during the initial postirradiation period. The content of malonic dialdehyde increased immediately after irradiation and somewhat decreased during the first 24 h. In 24 h, there observed a radiation-induced increase in the diene conjugate content in the liver and thymus of rats, against the background of low activity of such antioxidation system enzymes as glutathione transferase, glutathione reductase and catalase. PMID- 1496114 TI - [Effectiveness of correcting radiation injuries of the thymic endocrine function by T-activin in conditions of reduced postradiation hypercorticism reaction]. AB - T-activin administered to rats after exposure to whole-body 1.5 Gy neutron- and 6 Gy X-radiation increases considerably the thymosin-like serum activity, accelerates cellularity restoration in the thymus and spleen, but does not influence the survival rate. Ionol administered prior to X-irradiation reduces the postirradiation hypercorticism reaction and the indirect effect of radiation on lymphoid organs which it is responsible for. The combined injection of ionol and T-activin increases the thymosin-like serum activity and spleen cellularity to the highest possible level and increases the survival rate of rats from 24 to 64 per cent and the lifespan up to 6 days. PMID- 1496115 TI - [Redistribution of alimentary vitamin E in tissues of irradiated rats]. AB - The data are presented in this paper concerning the content of lipopigments, vitamin E and malondialdehyde (MDA) in the brain and liver of rats. Excess vitamin E delivered with food was shown to be bound in tissues into complex with MDA. It is suggested that it is a labile form that reserves vitamin E. Irradiation of rats caused impairment of these complex and release of vitamin E, as well as a decrease in the lipopigment fluorescence and increase in the MDA content. PMID- 1496117 TI - [Neurological symptomatology in cats irradiated under hypoxia conditions and tissue basophils of the skin]. PMID- 1496116 TI - [State of cellular immunity effectors of the lung after inhalation of 239Pu polymer nitrate]. AB - Wistar rats, who inhaled 239Pu (IV) at a dose that did not reduce the average life expectancy (the initial level in the lung was 0.77 kBq) did not exhibit any essential changes in the quality and functional activity of the alveolar macrophages. Revealed were the injuries to cells of bifurcation lymph nodes, the severity of which was a function of dose absorbed in the lung. PMID- 1496118 TI - Nutrition and magnesium absorption: a review. AB - This paper reviews the evidence that certain dietary components can affect intestinal absorption of magnesium. Increased intakes of protein and fructose improve apparent magnesium absorption (magnesium intake minus fecal excretion) in humans, whereas a lowering effect occurs with consumption of cellulose and phytate. Although dietary concentrations of lactose, fat, calcium and phosphate have clear effects on magnesium absorption in experiments with rats, the impact of these nutrients on magnesium absorption in humans remains unsettled. Mechanisms underlying the effects of dietary components on magnesium absorption in humans are generally poorly understood. A change in magnesium absorption not necessarily results in a change in magnesium retention. When consuming practical diets, the fall of apparent magnesium absorption caused by phytate and cellulose is generally compensated by increased magnesium intake due to high magnesium concentrations in phytate- and cellulose-rich products. Furthermore, to maintain homeostasis, urinary magnesium excretion will be raised after stimulation of apparent magnesium absorption and it will be lowered after impairment of apparent magnesium absorption. Thus, the effects of dietary components on magnesium absorption probably are critically important only at low intakes of magnesium. At low magnesium intakes, differences in magnesium absorption may be expected to influence magnesium retention and thus can either induce or abolish magnesium deficiency. PMID- 1496119 TI - Women's workload and its impact on their health and nutritional status. AB - This paper highlights various issues in relation to the workload of women in developing countries and its impact on health and nutritional status. The determining factors in women's workload and work-time and the methods employed for assessment are described. The drawbacks of the methods used and the resulting inconsistencies in the data are reviewed. How women are subjected to different health stresses owing to their productive and reproductive roles has been examined under three categories of work: economic, domestic and agricultural. The interaction of women's workload and health is complex and multifactorial owing to variations in the environment and socio-economic conditions within developing countries. There is a critical need to re-examine the assumptions existing about women's workload in programmes aimed at reducing work-time and workload of women in developing countries. PMID- 1496120 TI - Host-microflora correlations in infant nutrition. AB - The intestinal microflora represents an enormous cell mass and has a high metabolic capacity. The symbiotic efficacy of these microbes in humans is still a matter of discussion. Of particular interest, from a biogenetic point of view, are potential symbiotic relations between the bifidobacterial microflora and the breast-fed infant. Our group has conducted studies related to this topic; they were aimed at determining the dimension of microbial assimilation by the host. Our studies with 15N-labeled bifidobacteria have shown that the bifidobacterial microflora is capable of upgrading nonessential nitrogen such as urea nitrogen for the synthesis of microbial protein. Oral single pulse labelings with 15N labeled bifidobacteria were absorbed to approximately 90% and retained in the infant's protein pool to approximately 70%. These findings demonstrate the high intensity of the substrate flow from the microflora to the host. This might become important under conditions of marginal food protein intake or during periods of accelerated growth. PMID- 1496121 TI - Selective changes in mouse behavioral development after prenatal benzodiazepine exposure: a progress report. AB - 1. Animal studies of the effects of early exposure to CNS agents devoid of a major teratogenic potential must assess possible deviations from normal behavioral development in both a stage-specific and a behavior-specific fashion; several experiments on prenatal benzodiazepine (BDZ) exposure are reviewed, illustrating such an assessment strategy and discussing caveats on experimental designs and statistical analysis. 2. The offspring of mouse dams treated in late pregnancy with oxazepam (15 mg/kg p.o. twice daily on days 12-16) show a mild and reversible impairment in somatic and neurobehavioral development which is unlikely to be responsible for a series of other more specific changes. 3. The treatment produces a selective reduction of locomotor activity and amphetamine hyperactivity at the end of the second postnatal week, as well as a selective impairment of active avoidance at the young adult stage, in the absence of similar changes in scopolamine hyperactivity and passive avoidance. 4. The treatment also prevents the appearance at 28 days of morphine hyperactivity and of rebound hyperactivity after muscimol depression, without modifying the developmental profile of pain reactivity and of morphine and muscimol analgesia. 5. Young adult females previously exposed to oxazepam in utero show a marked enhancement of maternal aggression towards male intruders; mother-pup interactions are also modified, leading either to reduced or to exaggerated maternal care as a function of fostering procedures. 6. Overall, several effects of prenatal BDZ exposure appear to be amenable to modifications in monoaminergic system functions and/or to an accelerated development of GABAergic mechanisms; some of the changes in social and parental interactions, however, point to subtle modifications in the balance between different components of the fear-defensive repertoire, possibly due to an altered stimulus reactivity by mechanisms which are still poorly understood. PMID- 1496122 TI - Do biochemical factors play a part in postnatal depression? AB - 1. There are major changes in progesterone, oestrogen, cortisol and beta endorphin level associated with parturition, and as all these can be psychoactive it is likely that they contribute to the mood changes that can occur at this time. However evidence for their involvement is, at present, indirect. 2. Postnatal depression itself appears to be a heterogeneous condition with different times of onset, and it is probable that various biological and social factors play a role to a differing degree in different individuals. 3. About half of postnatal depression appears to arise in the first two weeks after childbirth. Some cases follow a period of early euphoria. 4. A different subgroup is associated with thyroid dysfunction, which peaks two to five months postpartum. 5. The tyramine test does not predict vulnerability to postnatal depression. 6. It is suggested that in future research the time course of onset of the depression, and the nature of the mood changes that occur in the first postpartum week, are investigated as possibly relevant variables. PMID- 1496123 TI - Neuroendocrine markers of serotonin responsivity in depression. AB - 1. Studies of the biochemical mechanism of action of antidepressant drugs show that virtually all drugs, regardless of acute biochemical effects, result in the down regulation of CNS beta-1 adrenergic, serotonin-2 (5HT2), and perhaps 5HT1A receptors in rats in a time course which parallels the onset of antidepressant action in patients with major depressive disorder. 2. Recently, neuroendocrine techniques have been described which allow the study of 5HT receptor subtypes in man. These include fenfluramine-induced changes in ACTH, cortisol and prolactin secretion (perhaps for 5HT2 receptors) and ipsapirone-induced changes in ACTH and cortisol (for 5HT1A receptors). 3. Depressed subjects treated with antidepressants down regulate these markers of both 5HT2 and 5HT1A receptors in a time course consistent with their recovery from depression. 4. Studies in progress are attempting to demonstrate links between these receptor changes and clinical antidepressant responses. PMID- 1496124 TI - Efficacy and tolerability of flupenthixol decanoate in the treatment of depression and psychosomatic disorders: a multicenter trial in general practice. AB - 1. A number of controlled as well as uncontrolled studies indicate that flupenthixol in a low-dose regimen is effective in treating syndromes with depression, anxiety, and psychosomatic disorders. 2. In view of the low compliance rates among patients suffering from depressive syndromes, the author evaluated the efficacy and tolerability of flupenthixol decanoate i.m. in an unselected collective of such patients treated in general practices. 3. Flupenthixol decanoate i.m. induced remission in 25% of patients suffering from chronic pain, in 29% of patients with psychosomatic disorders. Patients with depression and anxiety remitted in 27% of the cases. Therapeutic benefit was seen in more than 90% of the patients. 4. The best results were observed in patients 1) who had not been treated with psychotropic drugs before, 2) whose disease had a duration of less than one year, 3) who were under 40 years of age, and 4) who were treated with a dose lower than 0.5 ml (10 mg flupenthixol decanoate). PMID- 1496125 TI - Valproate treatment of mania. AB - 1. Acute as well as prophylactic effects of the anticonvulsant valproate are described in patients with mania and bipolar affective psychoses. 2. In a long term evaluation of valproate prophylaxis ranging up to 14 years, an average improvement of the phase chart of 12 patients was observed by a factor of 12. 3. The mode of action of this effect appears to be related to the GABAergic properties of the compound. PMID- 1496126 TI - Neuropsychological indicators of the vulnerability to schizophrenia. AB - Schizophrenia is associated with enduring deficits in neuropsychological functioning. It is widely undecided if the various aspects of neuropsychological impairment are a consequence of the disorder or if they are also present premorbidly and in populations at increased risk for schizophrenia (vulnerability markers). Neuropsychological deficits in healthy relatives of schizophrenic patients who are at an elevated risk for schizophrenia and who did not yet pass the period of risk would indicate that these deficits are vulnerability markers. This hypothesis was tested for three neuropsychological paradigms which have been proven to distinguish schizophrenic patients from controls. 33 siblings of drug free schizophrenic probands revealed deficits has compared to 33 matched healthy controls in a blurred single target version of the Continuous Performance Test and in a multiple item version of the Span of Apprehension Test but not so in less difficult versions of both tests or in the time needed to react to stimuli with shifting modality. PMID- 1496127 TI - Actions of oxaprotiline in the rat hippocampal slice. AB - 1. Recordings were obtained from transverse slices of rat hippocampus, which were placed in a perfusion chamber and superfused with oxygenated artificial cerebrospinal fluid. 2. The effects of 10 microM (+)- or (-)-oxaprotiline applied by the bath were examined on the population spike, postsynaptic excitability in low Ca2+-high Mg2+ medium, the epileptiform discharge in Mg2+-free medium and long-term potentiation (LTP). Only the last paradigm (LTP) was significantly enhanced by (+)-oxaprotiline. 3. In rats chronically injected with (+) oxaprotiline, neither LTP nor the actions of a variety of neurotransmitters in low Ca2+-high Mg2+ medium were significantly altered. 4. Intracellular recordings showed a small depolarization (3.5 +/- 1.6 mV) in response to 10 microM (+)- or ( )-oxaprotiline. Neither input resistance nor inward rectification, long-lasting afterhyperpolarization or accommodation were significantly altered. 5. Acute application, but not chronic treatment with (+)-oxaprotiline affects long-term potentiation in the hippocampal slice, presumably due to an effect on gabaergic inhibition. PMID- 1496128 TI - Chronic clozapine treatment down-regulates serotonin 5-HT-1c receptors in rat brain. AB - 1. The effects of chronic treatment with the atypical antipsychotic, clozapine, and classical antipsychotic, haloperidol, on serotonergic 5-HT-1c and dopamine D2 receptors in rat brain were studied with radioligand binding methods. 2. Two weeks' treatment with clozapine did not alter striatal D2 receptor characteristics measured with 3H-spiperone, but caused a 54% down-regulation of 3H-mesulergine binding to 5-HT-1c receptors in choroid plexus. 3. In contrast, two weeks' treatment with a classical neuroleptic, haloperidol increased significantly D2 receptor number in striatum, but had no effect on 5-HT-1c receptor binding. 4. In conclusion, alterations of 5-HT-1c receptor characteristics after chronic clozapine treatment may represent a mechanism that contributes to the unique clinical profile of this antipsychotic drug. PMID- 1496129 TI - Effect of lithium on rod photoreceptor rhodopsin-coupled G-protein (transducin). AB - 1. Lithium was known to inhibit both adrenergic and cholinergic agonist-induced activation of G-proteins in cerebral cortex. 2. Doly et al (1989) observed that lithium reduced the b-wave of the electroretinogram and suggested that the effect was due to inhibition of G-protein in photoreceptor cells. 3. This study was undertaken to test this hypothesis directly on photoreceptor cell membranes. Rod disk membranes containing the visual transduction machinery were isolated in the dark and the effect of lithium was tested on (a) activation by bright light of G protein-mediated cyclic GMP hydrolysis, (b) light sensitivity of the activation, (c) the lifetime of the light-activated receptor, and (d) light activation of GTP gamma-S binding to the membranes. 4. None of these processes were affected by lithium. It is therefore concluded that the effects of lithium on the b-wave of the electroretinogram should be due to influences on G-proteins in other parts of the retina. PMID- 1496130 TI - Brain neuropeptides: changes by treatment with the convulsants pentylenetetrazole and bicuculline. AB - 1. The effects of chemically induced convulsions, clinically similar to those elicited by electroconvulsive treatment (ECT), on brain regional distribution of neuropeptide Y-, neurokinin A-, substance P- and neurotensin-like immunoreactivities were studied in the rat. 2. Pentylenetetrazole (PTZ) and bicuculline (BIC) were used to induce grand mal seizures. Rats were divided into three groups receiving one of the following treatments: Saline, PTZ (45 mg/kg) or BIC (1.5 mg/kg). 3. After sacrifice by focused microwave irradiation, brains were dissected, peptides extracted and measured by specific radioimmunoassays. 4. Repeated grand mal convulsions induced by PTZ, in similarity to ECT, markedly increased NPY-LI concentrations in frontal cortex and hippocampus. In contrast to ECT, no changes in NKA- or SP-LI levels were seen. NT-LI was lowered in striatum. 5. Bicuculline effects were more circumscribed: some animals developed grand mal and died while convulsing (peptides not measured), others did not develop generalized seizures and were sacrificed after the fourth treatment. 6. The results demonstrate a similar effect of PTZ and ECT on regional NPY-LI concentrations and raise the possibility that grand mal, regardless of etiology, is necessary for effects on peptides. PMID- 1496131 TI - Accommodating our nurses ... a question of quality. PMID- 1496132 TI - Selected public hospitals trial: the 38-hour week. PMID- 1496133 TI - Nursing informatics: how does it affect nursing practice? PMID- 1496134 TI - Humanising the shiftwork systems. PMID- 1496135 TI - Choice between delayed reinforcers in an adjusting-delay schedule: the effects of absolute reinforcer size and deprivation level. AB - Choice between two reinforcers differing in magnitude and delay was investigated in rats using an adjusting-delay discrete-trials schedule in which the two reinforcers were associated with two levers (A and B). The delay to Reinforcer A (the smaller reinforcer) was always 2 sec, whereas the delay to Reinforcer B was varied in accordance with the distribution of choices in successive blocks of trials. In Experiment 1, the mean delay to the large reinforcer during the last 5 of 60 training sessions was greater when the rats were maintained at 80% than when they were maintained at 90% of their free-feeding body weights. In Experiment 2, the delay to the larger reinforcer was greater when the two reinforcers consisted of one and two 45-mg food pellets than when they consisted of three and six pellets. The results are consistent with a model of "self control" which posits hyperbolic relations between reinforcer value and reinforcer magnitude, and between reinforcer value and delay of reinforcement. PMID- 1496136 TI - Successive negative contrast in one-way avoidance learning in rats. AB - In three experiments, successive negative contrast was examined in one-way avoidance learning. Reward magnitude in first (pre-shift) and second (post-shift) phases was manipulated by time spent in the safe compartment. Experiment 1 demonstrated that when time in the danger compartment was held constant, a group shifted from a large reward--30 sec spent in the safe compartment--to a small reward--1 sec--showed poor performance and longer response latency than a group conditioned with the small reward in both phases. Experiment 2 replicated this effect with a less intense shock and also demonstrated that a group shifted from large to small reward performed more poorly than a group exposed to large reward- 30 sec--in both phases. Finally, Experiment 3 showed that changes in intertrial interval, defined as total time spent in the safe compartment and the danger compartment before the onset of the warning signal, were not responsible for this contrast effect. These results suggest that time spent in a safe place can act as appetitive incentive during one-way avoidance learning. PMID- 1496137 TI - Delayed-matching-to-sample by marsh tits and great tits. AB - The ability of two species of tits to remember the location and/or features of an object was tested in a delayed-matching-to-sample procedure. Three values of retention interval between presentation of the sample stimulus and the choice--30 sec, 5 min, and 15 min--were used. Both species performed at above-chance level at all retention intervals, and there was no significant decline in accuracy with increasing interval. A pool of 100 stimulus objects was used, but the results of control trials indicated that the birds responded primarily to location rather than stimulus features of the object itself. Although the food-storing marsh tit tended to perform at a higher level than the non-storing great tit, the only significant difference between the species was in the first 50 trials of the first treatment, when the birds were acquiring the task. The results are discussed in relation to the hypothesized special memory capacity of food-storing birds. PMID- 1496138 TI - Reciprocal overshadowing between intra-maze and extra-maze cues. AB - In three experiments, rats learned a maze discrimination where the location of food was defined either by reference to extra-maze cues alone, or by both extra- and intra-maze cues. Experiment 1 confirmed earlier results in showing that the presence of intra-maze cues failed to overshadow learning about extra-maze cues, in spite of the former's apparently greater salience. Experiment 2, however, suggested that this result was an artefactual consequence of differences between groups in the proportion of reinforced and unreinforced trials during the course of discriminative training. In Experiment 3, the discrimination was taught by a series of reinforced and unreinforced placement trials, and a significant overshadowing effect was observed. Intra-maze and extra-maze cues seem to compete for association with reinforcement in exactly the same way as any other cues. PMID- 1496139 TI - The role of instrumental responses in memory retrieval in a T-maze. AB - Retrieval of the memory of non-reward on a rewarded trial was investigated here employing rats in a T-maze. A forced choice procedure was used. The daily rewarded (R) and non-rewarded (N) trials always occurred in a fixed order, two R, four N, and finally two R, i.e. the series was R1-R2-N1-N2-N3-N4-R3-R4. In an original acquisition phase. Trial N4 of the series having occurred in a particular spatial alternative, e.g. left, it was followed by R3 either in the same alternative, Groups C and T, or in the opposite alternative, Group R. Group T, unlike Groups C and R, received a relatively long intertrial interval between N4 and R3. In a shift phase, groups were treated as in original acquisition except that the long intertrial interval (Group T) and the change in response (Group R) now occurred between R3 and R4 rather than N4 and R3. The major finding in original acquisition was slower running by Groups T and R than by Group C on Trials N2, N3, and N4. In shift, differences between the groups disappeared. These findings are consistent with the hypothesis that response-produced cues contribute to memory retrieval. PMID- 1496140 TI - Inherent radiosensitivity and split-dose recovery in plateau-phase cultures of 10 human tumour cell lines. AB - The radiation response of 10 human tumour cell lines, eight of them established in our Institute, was analysed. Single dose acute survival curves were constructed and fitted with the linear-quadratic (LQ) model. The mean inactivation dose (D) was also calculated, together with D(o) and n. In order to measure both split-dose recovery and delayed plating recovery of plateau-phase cells, confluent cultures were subjected to two doses of 2 Gy 24 h apart, and plated 24 h later, simulating clinical fractionation. Survival of these cells (S2 x 2) was compared to that following 4 Gy given to cells plated at low density and an overall recovery factor (RF) was derived, including both types of recovery. S2 x 2 and RF were compared to the intrinsic radiosensitivity parameters. The three melanoma cell lines differed in radiation response, and the three squamous cell carcinoma cell lines were rather radioresistant. The neuroblastoma cell line was highly sensitive, yet it expressed the highest beta and the highest RF. Using a non-parametric correlation test, S2 x 2 was found to be related to D, whereas RF was not related to the radiosensitivity parameters. However, the two cell lines with the lowest D and the lowest S2 expressed the highest RF. These results suggest that radiosensitive cell lines may have a considerable capacity to recover if confluent cultures are exposed to fractionated irradiation. The overall recovery factor (RF) used here is proposed as a useful measure of cellular recovery. PMID- 1496141 TI - Low dose preoperative radiotherapy for carcinoma of the oesophagus: results of a randomized clinical trial. AB - One-hundred-and-seventy-six patients with potentially operable squamous cell carcinoma or adenocarcinoma of the middle or lower thirds of the oesophagus were randomly assigned to preoperative radiotherapy or surgery alone. Patients assigned to the radiotherapy arm received 20 Gy in 10 treatments over 2 weeks, using parallel opposed 4 MV beams. The preoperative radiotherapy was not associated with any significant acute morbidity or any increase in operative complications. The median survival of the overall group of 176 patients was 8 months, and the 5-year survival was 13%. There was no significant difference in the survival of the 90 patients who received preoperative radiotherapy and the 86 who were managed by surgery alone. Proportional hazards analysis identified lymph node involvement, high tumour grade and male sex as significant adverse prognostic features, but the treatment option assigned had no prognostic significance. It was concluded that low dose preoperative radiotherapy offered no advantage over surgery alone. PMID- 1496142 TI - Digiplot: a PC programme for drawing tumour volumes for radiation therapy treatment planning using computed tomography images. AB - Computed tomography (CT) provides explicit information for tumour localisation. However, CT data are displayed in the transverse plane, whereas on the Radiotherapy Simulation films, radiation portals are commonly directed into anteroposterior and lateral planes. Using present day radiotherapy planning computers, it is possible to read in the CT data to determine the tumour volume in anterior/posterior and lateral directions and to perform dosimetry calculations. In cases where the digital computer data cannot be used directly by the radiotherapy planning computer, (for example, owing to compatibility problems) the radiation oncologist must transfer information about tumour location from the CT hard copy images to the longitudinal planes of the simulation film by hand. This manual data transfer can now also be performed using the new personal computer programme, Digiplot, which we have developed and is described below. The application of Digiplot to the head and neck area has shown that it complies with the accuracy requirements laid down by the radiation oncologist. The clinical impact of Digiplot was tested on ten patients with a brain tumour. In two cases, Digiplot detected errors which had not been observed using the conservative (manual) method. PMID- 1496143 TI - Thalassemic osteoarthropathy treated by radiotherapy. PMID- 1496144 TI - Rapid repopulation in radiotherapy: a debate on mechanism. PMID- 1496145 TI - Parotid gland function following radiotherapy. PMID- 1496146 TI - Three-dimensional dose mapping from gamma knife treatment using a dosimeter gel and MR-imaging. AB - A new method has been investigated for the mapping of dose distributions in three dimensions delivered by the Leksell gamma knife. The irradiation unit is used to selectively treat small volumes in the brain with single high doses of ionising radiation--a treatment procedure known as radiosurgery. The dosimetry method investigated utilises a dosimeter gel consisting of ferrous sulphate solution and agarose which is, prior to irradiation, loaded into a cavity in a spherical phantom. Chemical changes induced in the gel by the radiation are measured by means of an MR-scanner. This imaging method permits rapid evaluation of the dose distribution in an irradiated volume. It thus offers a potential verification of individual radiation intracranial target treatment regimes as well as quality assurance measurements, assuming that the precision and accuracy of the dose mapping are adequate. The dose and its distribution registered by the gel dosimeter, in this initial experiment, are in good agreement with corresponding computed data obtained with the KULA treatment planning system of the gamma knife. The gel has thus the potential of being an attractive alternative dose mapping method to those used at present in radiosurgery, i.e. radiographic film and small ionisation chambers. The precision of the dosimeter gel is, however, not yet sufficient high to be used as a basic dosimetry system for the gamma knife. PMID- 1496148 TI - Radiation therapy of stage I breast cancer: analysis of treatment technique accuracy using three-dimensional treatment planning tools. AB - This paper presents the routine implementation of a method for use of three dimensional (3-D) treatment planning for breast cancer patients with node negative disease, treated with breast conserving surgery. The patients were positioned on a device which fitted a CT aperture with a diameter of 70 cm. A patient reference system was defined by the mamillary plane and the sternum midline. Eight to twelve CT images per patient were taken. The target volume was defined in several CT slices. The treatment planning was made with a 3-D treatment planning system; the treatment technique was isocentric with tangential fields. The patient position was the same at the CT scanner and during the treatment. Four to six portal films per field per patient were routinely taken. The reproducibility of the set-up was investigated on 20 consecutive patients: the treatment-to-treatment variation results were related to the margin of the target. The comparison between treatment planning and portal films gave information about the isocenter displacement. No large discrepancy between measurements on simulator film and on portal films was found. Based on the presented results the described treatment technique has been introduced as part of a routine clinical practice at our institution. PMID- 1496147 TI - Incompletely resected advanced squamous cell carcinoma of the head and neck: the effectiveness of adjuvant vs. salvage radiotherapy. AB - Between 1982 and 1988, 441 patients were treated at the Medical College of Virginia for AJC Stage III and IV squamous cell carcinoma of the head and neck. We report here on 84 patients whose tumors were incompletely resected based on histopathological margins of 1 mm or less. Of these 84 patients, 49 were treated with surgery alone and 35 received immediate postoperative irradiation to doses of 50-70 Gy. The two patient groups are comparable with respect to stage of disease, age, male/female and racial ratios. This retrospective analysis, based on follow-up of 24-110 months, gives actuarial locoregional tumor control and survival data. The local control and disease-free survival rates in the combined modality group are significantly superior at the p = 0.0006 and p = 0.0003 levels, respectively, relative to the group treated with surgery alone. Patients in the combined modality group also experienced a significantly improved adjusted and overall survival, p = 0.005 and p = 0.01, respectively. The administration of postoperative irradiation was not associated with an increased rate of complications. The benefit of radiotherapy on survival was only seen when given as postoperative treatment but was lost in patients treated for salvage after tumor recurrence. PMID- 1496149 TI - Effects of position and mattress overlay on sacral and heel pressures in a clinical population. AB - A comparison of pressure reducing properties of alternating air, static air, and water mattress overlays was conducted with 57 patients in a surgical intensive care unit. Sacral and heel pressures in both recumbent and semi-Fowler's positions were tested for each surface using a repeated measures design. Mean pressures for the alternating air mattress were significantly higher than pressures with other surfaces, regardless of position or site. There were significant main effects for position and site, with higher pressures in the semi Fowler's position and at the sacral site. A significant interaction between surface, site, and position was found. Pressure sores developed in eight patients, but the incidence was not significantly different across groups. A pressure measuring device constructed from available clinical materials proved to be both sensitive and reliable. The findings suggest alternating air overlays should be avoided, and that positioning and periodic position change to reduce sacral pressures for patients requiring prolonged upper body elevation is important. PMID- 1496150 TI - Preadmission self-instruction effects on postadmission and postoperative indicators in CABG patients: partial replication and extension. AB - Fifty adult coronary artery bypass graft surgery patients were randomly assigned to preadmission self-instruction or posthospital admission instruction of therapeutic exercises (e.g., coughing). Self-instructed subjects reported higher positive mood scores, performed correctly significantly more exercise behaviors, and required less teaching time following hospital admission. Postoperatively, no group differences were found on mood states, physical activity, analgesic use, or length of hospital stay. Both groups, however, tended to use less pain medication than that reported by other researchers and experience shorter hospital stays than that assigned under the Diagnostic Related Groups prescription. PMID- 1496151 TI - The stress response of mothers and fathers of preterm infants. AB - Differences in neonatal intensive care unit (NICU) environmental stress, uncertainty, and anxiety of 23 mothers and fathers (couples) whose premature infants were hospitalized in an NICU were explored. Alterations in the parental role were found to be stressful for both mothers and fathers, with mothers reporting significantly greater stress in this area than did fathers. Stress and uncertainty decreased significantly over time. Mothers and fathers did not differ in level of anxiety. Findings suggest that both mothers and fathers are distressed by the admission of a premature to an NICU; however, mothers may be more distressed by certain aspects of the experience. PMID- 1496152 TI - The organizational environments and services of VNAs and hospital-based home health care agencies. AB - Visiting Nurse Associations (VNAs) and hospital-based home health care agencies (HBHHAs) were used to explore the impact of organizational environments on agency services. Disproportionate stratified random sampling, based on type and region of agency, was used to select the agencies. Seventy-three percent (120 HBHHAs and 156 VNAs) responded to the mail survey. Differences were found in the environments of the two types of agencies in funding and referral sources, amount of competition, accreditation by external bodies, and involvement in professional organizations. In terms of services, HBHHAs provided more types of high-tech services and were more likely to use external arrangements to provide services than VNAs. The organizational environment did have an impact on agency services. Medicare funding and referral sources, as environmental factors, had an impact on agency services. PMID- 1496153 TI - Perceived risk of infection and attitudes toward risk groups: determinants of nurses' behavioral intentions regarding AIDS patients. AB - The relationship of perceived occupational risk of AIDS and attitudes toward AIDS risk groups to behavioral intentions regarding the care of AIDS patients was examined among nurses (N = 496) residing in a selected area of New Jersey, a state with a relatively high number of reported AIDS cases. Hierarchical multiple regression analyses on anonymous mail survey responses revealed that, controlling for AIDS knowledge and years of education, nurses who perceived that caring for AIDS patients increased their risk of HIV infection scored higher on an index of intentions to avoid AIDS patient care. In addition, nurses who expressed more negative attitudes toward intravenous drug users or homosexuals were more likely to report similar intentions to avoid AIDS patient care. The implications of these findings for efforts to increase nurses' ability and willingness to provide quality care to persons with AIDS are discussed. PMID- 1496154 TI - Divergent productive thinking factors and accuracy of nursing diagnoses. AB - Theories of diagnosis in nursing (Carnevali, 1983; Gordon, 1982) and a model of intelligence (Guilford, 1979) were integrated to provide a theoretical basis for this study. In contrast to previous studies, accuracy of nursing diagnoses was measured as a continuous variable. It was hypothesized that three factors of divergent productive thinking, fluency, flexibility, and elaboration, would correlate positively with accuracy of nursing diagnoses. The sample consisted of 86 female nurses, graduates of generic baccalaureate programs with 1 to 5 years experience, who met the criterion of knowledge. Three written case studies (CS1, CS2, CS3) served as the criterion for accuracy. With CS1, none of the hypotheses were supported. With CS2, the three hypotheses were supported (p less than .05) and 10% of the variance was explained by one factor, fluency (p less than .01). With CS3, elaboration and accuracy were correlated (p less than .05). The findings provide beginning support for inclusion of exercises for divergent thinking in nursing education and practice. PMID- 1496155 TI - Focus on psychometrics. Aggregating family data. AB - Instruments to collect data about families are often administered to all or some individuals within the family. Researchers may wish to use these individual scores to describe the family. The purpose of this article is to describe the special issues with aggregation of data when only a small number of family members are used as respondents. A refinement of the definition of aggregation for family researchers is proposed to assist researchers to focus on specific issues when data are to reflect subgroups within the family. A few examples of changes in findings are reported to illustrate the effects of different aggregation schemes when two members of the family are used as respondents. PMID- 1496156 TI - Re: Definitions of grief. PMID- 1496157 TI - An update from Dr. Benoliel. PMID- 1496159 TI - Sjogren's syndrome. PMID- 1496158 TI - Sjogren's syndrome: historical overview and clinical spectrum of disease. AB - Sjogren's syndrome is a chronic autoimmune and inflammatory disease characterized by lymphocyte proliferation that progressively destroys exocrine glands. The lymphocytes can infiltrate other and more vital organs and may at times become malignant. Another name for this disease is autoimmune exocrinopathy. It was first described over 100 years ago both as a benign syndrome of oral and ocular dryness and also as a lymphoid malignancy. Thus, Sjogren's syndrome is related to the autoimmune rheumatic diseases, as well as to lymphoid B-cell malignancies. PMID- 1496160 TI - The immunogenetics of Sjogren's syndrome. AB - The fact that patients with SS, either primary or associated with another connective tissue disease, show a striking tendency toward familial aggregation of SS, other autoimmune disease and autoantibodies suggest a role for genetic factors in the pathogenesis of this disease. What these factors are is as yet not known; however, it is clear that autoantibodies found in high frequency in SS, specifically anti-Ro and anti-La, are associated with HLA class II alleles, found at the HLA-DQA1 and DQB1 loci, which have in common the presence of specific amino acid residues that are found in the second hypervariable region of the first (outermost) domain. Additional roles for T-lymphocyte receptor and immunoglobulin genes are also suggested. Family studies, however, indicate the presence of an additional autosomal dominant gene(s), not linked to HLA or immunoglobulin heavy or light chain genes, in predisposition to SS. Identification of this additional genetic factor(s) should provide important clues in the pathogenesis of SS. PMID- 1496161 TI - Antinuclear antibodies in Sjogren's syndrome. AB - The definition and characterization of the reactivity of ANA in patients with SS are greatly improved with the current advances in cellular and molecular biology. Based on the characteristic autoantibody profiles in different systemic rheumatic diseases and the nature of the defined autoantigens, it has been proposed that the polyclonal autoimmune response is induced and maintained through an antigen driven mechanism. The autoantigens are presented in the cell as components of large particles or structures composed of protein-protein or RNA-protein complexes; however, the role of these autoantibodies in the etiology and immunopathogenesis of SS remains to be determined. PMID- 1496162 TI - Salivary and oral components of Sjogren's syndrome. AB - The intraoral symptoms and signs of SS are not specific to SS, being shared with other conditions in which salivary function is diminished. The decrease in saliva causes chronic oral discomfort and functional problems and predisposes patients to dental caries and oral candidiasis. Many methods have been used to assess SGs in SS objectively, but at present a labial salivary gland biopsy specimen showing focal lymphocytic sialadenitis provides the best diagnostic criterion for the salivary component of SS, in terms of its disease specificity, convenience, availability, and low risk. The treatment of xerostomia in patients with SS consists of (1) preventing new and recurrent dental caries by frequent and regular application of topical fluoride, careful dental supervision, and avoidance of sucrose and other metabolizable carbohydrates between meals; (2) reducing oral symptoms by diagnosing and treating oral candidiasis (repeatedly if necessary); and (3) attempting to replace lost saliva by stimulating salivary secretion with physiologic sialogogues or pilocarpine, or if adequate amounts of saliva cannot be stimulated, using some form of saliva substitute, especially for patients wearing complete dentures. PMID- 1496163 TI - Ocular manifestations of Sjogren's syndrome: keratoconjunctivitis sicca. AB - As part of the triad of Sjogren's syndrome (SS), keratoconjunctivitis sicca (KCS) can be found in virtually all SS patients. This term emphasizes not only the reduced tear production but also the pathologic changes in the epithelial cells of the ocular surface. The symptoms of dry eye may vary from one patient to another depending on the severity of dryness, the ability of the diminished tear film to moisten the ocular surface, and the patient's tolerance for ocular discomfort. Treatment of the dry eyes is remarkably effective, and most patients benefit from moisturizing eyedrops to replace their own deficient tears. Major issues include the pathogenesis of decreased tear flow and ocular surface disturbances, as well as the roles of wound healing agents and anti-inflammatory medications in KCS therapy. PMID- 1496164 TI - Cutaneous manifestations of Sjogren's syndrome. AB - The major mucous membrane and cutaneous manifestation of Sjogren's syndrome (SS) is xerosis. Severe dryness of the eyes, mouth, nasal passage, and vagina produce many annoying symptoms, including photophobia, burning and itching of the eyes, alterations in taste and smell, recurring nonallergic bacterial sinusitis rhinitis, and dysparunia. SS patients frequently complain of dryness of lips and soreness and a burning sensation of the tongue and oral mucosa. SS patients also complain of dryness of their hair and note a decrease in luster, and severe dryness of the skin is frequently accompanied by pruritus. PMID- 1496165 TI - Pulmonary and gastrointestinal manifestations of Sjogren's syndrome. AB - The respiratory system is frequently involved in primary SS but this involvement is rarely clinically significant. Its manifestations are secondary to desiccation of the tracheobronchial tree and lymphocytic infiltration of the lung parenchyma. The desiccation of the tracheobronchial tree gives rise to the most important clinical manifestation, dry cough (xerotrachea), but is rarely a cause of infection and obstructive airways disease. The lymphocytic infiltration of the lung parenchyma starts as lymphocytic alveolitis in a very large number of SS patients but rarely evolves into frank lymphocytic interstitial pneumonitis and fibrosis. Even more rare is the evolution of pseudolymphoma into malignant lymphoma. Pleurisy with or without effusion is not a frequent manifestation of primary SS. It occurs often in secondary SS and is due to the underlying rheumatic disorder. In general, secondary SS rarely has significant pulmonary manifestations other than those of the disorder it accompanies. The manifestations from the gastrointestinal system in patients with SS include mucosal dryness, accelerated dental decay, and enlargement of the major salivary glands, as well as dysphagia, nausea, epigastric pain, and dyspepsia. The dysphagia is probably secondary to esophageal dysfunction, and the gastric symptoms might be attributable to chronic atrophic gastritis. Whether the small bowel is affected in SS patients is not clear. Pancreatic involvement usually is being expressed as subclinical acute or chronic pancreatitis. Finally, the liver could be involved in SS patients, and some studies indicate that the pathogenic process responsible for the hepatic damage and for the salivary gland destruction could be similar. PMID- 1496166 TI - Central nervous system disease in Sjogren's syndrome. New insights into immunopathogenesis. AB - Although peripheral nervous system disease is a well-established complication of primary Sjogren's syndrome (SS), until relatively recently little attention has been focused on the central nervous system (CNS) complications of this disorder. The observations discussed in this article pertain to patients with primary SS in whom the presence of a second connective tissue disorder and other etiologies for neurologic disease have been rigorously excluded. In this article, the growing clinical spectrum of CNS manifestations, neurodiagnostic techniques, serologic analyses, and immunogenetic markers associated with this disorder are reviewed. PMID- 1496167 TI - Comparison of diagnosis and treatment of Sjogren's syndrome in Japan and United States. AB - Today, as with western countries, diagnosis and treatment of Sjogren's syndrome (SS) patients in Japan are carried out by a team effort. The clinical manifestations of Japanese SS patients are quite similar also. There are, however, several minor modifications in the diagnosis and treatment of SS patients in Japan, which are presented in this article. PMID- 1496169 TI - Treatment of the patient with Sjogren's syndrome. AB - SS is a systemic autoimmune disease characterized by lymphocytic infiltrations of lacrimal and salivary glands. Extraglandular organs including skin, nerve, lung, and kidney may be involved. At the present time, there remains a great deal of confusion regarding the precise definition of SS. As a result, both patients and clinicians frequently have a difficult time in making a specific diagnosis and instituting a specific plan of therapy. Regardless of the diagnostic label, all patients with significant eye and mouth dryness should receive conservative therapy of tear replacement and intensive oral hygiene. Based on the presence or absence of clinical or laboratory features of systemic autoimmunity, additional therapies may prove beneficial in controlling the symptoms and progression of SS. PMID- 1496168 TI - Diffuse infiltrative lymphocytosis syndrome: a disorder occurring in human immunodeficiency virus-1 infection that may present as a sicca syndrome. AB - Certain adults and children infected with the human immunodeficiency virus(HIV)-1 developed a disorder termed diffuse infiltrative lymphocytosis syndrome (DILS) that, although having certain similarities to classic Sjogren's syndrome, manifests distinctive clinical, serologic, immunologic, and immunogenetic characteristics. DILS is characterized by circulating CD8 lymphocytosis and apparently antigen-driven CD8 T-cell infiltration of salivary and lacrimal gland, pulmonary, renal, gastrointestinal, and breast tissues. The disproportionately greater degree of salivary gland enlargement and extraglandular disease, as well as the low frequency of autoantibodies and differing HLA associations, serve to distinguish DILS from classic Sjogren's syndrome. PMID- 1496170 TI - [25 years of the Journal of the School of Nursing of the Universidade de Sao Paulo: "a silver anniversary in a golden anniversary"]. PMID- 1496171 TI - [General qualifying exams: a report of experience at the doctorate level]. AB - This is a report of experience obtained on the occasion of General Qualifying Exams taken by candidates to the Doctoral degree in the Graduate Program of the School of Nursing at Sao Paulo and Ribeirao Preto, of the University of Sao Paulo. Documents concerning legal rules were consulted, along with relevant literature that permitted us to obtain in-depth information about the research lines, methods and activities used by nursing researcher, as a way of facilitating the collection of information about authors. We trust that this experience will help clarify the subject for colleagues who intend to take these exams. PMID- 1496172 TI - [An instrument for the nursing consultation of patients with arterial hypertension under outpatient treatment]. AB - The purpose of this article is to emphasize the nurse's role toward persons with arterial hypertension. Therefore it's introduced an application form that is used for nursing consultation to outpatients. PMID- 1496173 TI - [The universe of the entering freshman: a prospect of multiple challenges]. PMID- 1496174 TI - [The nursing consultation in geriatrics: the topics to be addressed in the physical examination--II]. AB - The author approaches physical exam in elderly and other items that are essential to nurses consultation. This article completes the topic Nurses consultation on Geriatrics--part I. PMID- 1496175 TI - [A descriptive study of the defining characteristics of nursing diagnosis: sexual dysfunction]. AB - The defining characteristics of the nursing diagnosis "Sexual Dysfunction" were gathered from NAAM assessment records. From this population 96 records with the defining characteristics of Sexual Dysfunction were selected. The 9 defining characteristics proposed by The North American Nursing Diagnosis Association were used as a framework for the data collection tool. The 3 most frequently defining characteristics were absence of sexual desire (71.9%), vaginal discharge (64.5%), and pain (44.8%). The authors concluded that 6 defining characteristics have not appeared; absence of sexual desire and vaginal discharge can be considered as minor characteristics. The authors recommend the implementation of other studies to clarify the subjective defining characteristics. PMID- 1496176 TI - [Occupational stress in the nurse of a central supply unit]. AB - The goals of this study were to characterize the central supply nurses to verify the nursing activities that are involved in occupational stress, and to lessen the stressors. Eight nurses comprised the sample; they were 25 to 30 years old, worked in the unit less than 5 years and they were satisfied with their job. The administrative area were the most mentioned stressor. The recognition and valorization of central supply area is an important aspect to diminish the nurses stress. PMID- 1496177 TI - [Leininger's transcultural theory]. AB - The authors make a short review of the development of Transcultural Nursing, present several major concepts and definitions as well as some major assumptions of this theory. Some considerations are made on the "Sunrise" Theoretical Conceptual Model of Transcultural Care Diversity and Universality, developed and used by Leininger since 1965 to the present. PMID- 1496178 TI - [Changes in the profile of the student in the School of Nursing of the Universidade de Sao Paulo in the 15 years from 1973 to 1988]. PMID- 1496179 TI - [The social and health policies in Brazil: a historical approach]. AB - The author makes an historical approach of the brazilian social and health policies, trying to co-relate them to the changes of the mode of production of each historical cycle. She intends to clarify that social policies represent the state "administration" of conflicts between classes and that health policies express social inequalities, showed in a different access to health utilities. PMID- 1496180 TI - [Transfusion risks and alternatives to transfusion]. AB - The emergence of the acquired immunodeficiency syndrome (AIDS) has fueled concerns of both physicians and their patients about safety of blood transfusions. Although AIDS has generated the most fear, the risk today is extremely remote (1/60.000 units of blood). The risk of transmitting infectious disease by homologous transfusion is decreasing, as more donor screening and testing measures are implemented. The blood supply is safer that at any time, but small transfusion risks exist. The most common problems associated with transfusions are temporary: one in 100-300 recipients will experience fever or rash. The biggest problem is a mismatch of the well-known ABO blood groups and once in every 100-400.000 transfusions the hemolytic reaction is fatal. Viral hepatitis is another serious and important risk. At present hepatitis seems to strike between 1 and 3 percent of transfusion recipients. Most, if not all, of transfusion-associated hepatitis cases are caused by hepatitis C virus. Cytomegalovirus can cause primary infection, reactivation or reinfection by transfusion. Immunosuppressed patients are more likely to develop more severe disease. Epstein-Barr virus does not seem to cause significant post-transfusion disease. Bacterial or protozoal infections are an infrequently encountered adverse effect of transfusion. However, some clinical cases document the potential hazard of blood components as a vector for bacteria or protozoa. Homologous blood transfusion down-regulates some immune functions. Host defences against malignancy and infection may in some instances be severely compromised by transfusions of homologous blood.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1496181 TI - [Usefulness and limitations of vaccination against influenza]. AB - Influenza viruses have caused major epidemics of respiratory disease and a high mortality in patients with advanced age and in those with underlying health conditions. It has been estimated in the USA that, during a moderate epidemic of influenza, there is an excess of 170,000 hospitalizations and approximately 20,000 to 40,000 influenza-associated deaths per years. Costs may exceed 1 billion dollars per year. Influenza viruses have been difficult to control because of a large animal reservoir and of the frequent change of the virus antigenic structure by major (shift) and minor (drift) variations. Current killed trivalent vaccines are made of two influenza A subtypes plus influenza B virus. Because of the antigenic variation, vaccine composition needs to be changed almost every year in order to contain the strains most likely to be effective. There are two types of vaccines--"whole" and "split". The latter has been treated to reduce pyrogenic components and is particularly indicated in children. Vaccine efficacy varies according to how closely the immunizing strains resemble the circulating wild strain. It also depends on the viral strains which had appeared in the preceding years (herd immunity), on the number of the doses administered and on the interval between the vaccination and the natural challenge. The antibody response to vaccine is short-lived. It is greatest in normal adults and lowest in aged and in immunosuppressed patients. Vaccination reduces clinical infections by 70-80% in children and adults, but only by 30% in elderly patients living in institutions.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1496182 TI - Herpes simplex pneumonia in a heart transplant recipient. AB - An unusual case of Herpes simplex virus (HSV) pneumonia in a heart transplant recipient receiving chronic immunosuppressive therapy is reported. This infection presented an indolent course manifested by a chronic left pulmonary infiltrate unresponsive to antibiotic therapy and mild hypoxemia. Death eventually occurred as a consequence of an other infectious complication of the postoperative period. The HSV etiology of the necrotizing pneumonia observed at autopsy was established on the basis of histologic findings. PMID- 1496183 TI - Serum albumin and others parameters in intravenous drug users HIV-infected. AB - In 37 intravenous drug users (IVDUs) in the first stages of HIV-infection (17 in stage II and 20 in stage III according to CDC), compared with 32 IVDUs HIV negatives, we found a significant decrease in circulating leucocytes (p less than 0.01), lymphocytes (p less than 0.005), platelets (p less than 0.005), serum albumin (p less than 0.005), and C3 (p less than 0.02) and significant increase in serum gammaglobulins (p less than 0.0005) and IgG (p less than 0.0005). On the other hand no difference was observed in hemoglobin and in IgA levels; nevertheless an inverse relationship between serum IgA and CD4+ lymphocytes was present in HIV-positive (HIV+) patients (r = -0.34; p = 0.04). This observation agrees with that is observed in the advanced stages of HIV-infection, which presents an increase in IgA serum levels. In these stages this fact could be due to a decrease of secretory IgA, with a deficient barrier effect; the consequent recirculation of intestinal antigens should enhance the antibody production, as well as serum IgA. In the IVDUs HIV-infected a reverse correlation between albumin serum levels and the length of HIV-positivity (r = -0.44; p = 0.008) and a direct correlation between albumin serum levels and circulating CD4+ lymphocytes (r = 0.37; p = 0.05) were present. There was no direct linear relationship between albumin serum levels and creatinine, on the contrary to what was observed in the control group. The decrease of albumin levels could have a prognostic value as in other clinical conditions, in which it is associated with a higher mortality risk. Many factors could act to decrease albumin levels, but the most important one is perhaps the malnutrition of HIV-infected patients that can also be present in the first stages of infection, negatively influencing the associated immunodeficiency. PMID- 1496185 TI - [Iproniazid-induced acute hepatitis]. AB - Many drugs can cause an acute liver damage. The patient history is the guideline for diagnosis. Iproniazid, a monoamine-oxidase inhibitor not for sale in Italy, can frequently cause severe acute hepatitis. A case of acute iproniazid-induced, hepatitis in which the course was favourable, is reported. PMID- 1496184 TI - [Presence and significance of anticardiolipin antibodies in infectious diseases]. AB - IgG and IgM anti-cardiolipin antibodies were measured, by an ELISA technique, in the sera of patients with B hepatitis (28), infectious mononucleosis (10), chicken pox (12), HIV infection (20), acquired toxoplasmosis (41) and other infectious diseases [HBsAg+ chronic hepatitis (5), brucellosis (6), herpes zoster (4), boutonneuse fever (3), viral pneumonitis (4), rheumatic fever (2)]. Increased levels of anti-cardiolipin antibodies (aCL), at least in one immunoglobulin class, were detected in 37 out of 135 patients [27.4%; range: 7.3% (in the patients with toxoplasmosis) -80% (in the patients with HIV infection)]. Low or medium titer aCL were present in 28 patients, high titer in 9 (6 with HIV infection, 2 with chicken pox and I with lymphoadenopathic toxoplasmosis). None of the manifestations associated with aCL was present in the aCL-positive patients. Finally, positivity for aCL didn't seem to modify the clinical picture and the prognosis of the infectious disease. PMID- 1496186 TI - [Imported malaria among immigrants in Italy, 1988-1990]. PMID- 1496187 TI - [Use of 99mTc-HMPAO SPECT in the study of AIDS-correlated dementia]. AB - AIDS dementia complex is a well-defined neurological manifestation of the HIV infection. Its anatomo-pathological pattern is cerebral atrophy, grey and white matter abnormalities and vascular changes, and the main symptom is progressive dementia. SPECT with Tc 99m HMPAO has proved to be an useful tool in studying Alzheimer and multi-infarct dementia, and its use has been recently proposed in AIDS-dementia. We studied with Tc 99m HMPAO 57 Pts (11 HIV+, 26 ARC, 17 AIDS) and control group of 7 drug-addicted seronegative Pts. We found positive results in 45% SPECT, 18% CT, 0% neurological tests of dementia in HIV+ phase, versus 52%, 41, 20% in ARC phase and 94%, 88% and 76% in AIDS phase, while all control Pts were negative. Control group is too small to exclude with all possibility of doubt cerebral blood flow impairment caused by drug damage but nevertheless we think that SPECT examination with 99 mTc HMPAO has an important role in assessing CBF changes in earlier stages of AIDS disease. These changes are probably forerunners of definitive cerebral damage and may be important markers of the advancement of disease. PMID- 1496189 TI - Assessing response bias in random-digit dialling surveys: the telephone-prefix method. AB - Knowledge of the characteristics of survey non-respondents is important to determine generalizability to the population of interest. In a recent random digit dialling survey of health behaviours only 73 per cent of the households contacted provided any information about household composition, and only 74 per cent of those actually completed the extended interview, for an overall response rate of 54 per cent. To identify possible biases we grouped all attempted phone numbers by their prefix, and looked for the association between the response rate for that prefix and other summary variables known about the prefix. A simulation study showed that the method can identify non-response biases if certain assumptions are correct. The analysis suggested that our survey data under represent older people and those with a college education. We found no significant biases in health behaviours, possibly because the basic assumptions did not hold. This method may assist in identification of non-response bias in other studies. PMID- 1496188 TI - [Monitoring of several hematological parameters of the erythroid series in patients with HIV infection treated with zidovudine]. AB - Haematologic toxicity is the most common adverse effect related to long-term administration of zidovudine (AZT). We evaluated the kinetics of modifications of some haematologic parameters of erythroid series in 65 patients with HIV infection treated with AZT for a mean duration of 7.6 +/- 4.7 months (13 of them with a previous diagnosis of AIDS, 34 with ARC, 18 asymptomatic or with LAS/PGL), in order to correlate the observation and the evolution of these laboratory changes with the onset of severe anaemia. The development of macrocytosis occurs in a large majority of AZT-treated subjects, in spite of folate and vitamin B12 supplementation; the monitoring of erythrocytes distribution according to cellular volume and cellular haemoglobin concentration makes it possible to early recognize the occurrence of modification in erythropoiesis. There is no correlation between an elevated mean corpuscular volume and the development of severe anaemia (Hb less than or equal to 9 g/dl) in an individual patient; a fall in the reticulocyte count appears to be the earliest peripheral blood sign of the development of bone marrow toxicity. PMID- 1496190 TI - Discriminant analysis when all variables are ordered. AB - Determination of the equation that relates an ordered dependent variable to ordered independent variables is sought. One solution, non-parametric discriminant analysis (NPD), involves obtaining the best monotonic step function by means of a computer search procedure. Although one can use alternative selection criteria in obtaining the equation, the illustrative examples use absolute distance. This paper compares the prediction procedures obtained from NPD with those from linear discriminant analysis, linear regression (with and without transformed variables), and logistic regression. We show that NPD is analogous to regression tree analysis with incorporation of ordered variables and monotonicity. We use various prediction functions to predict the example data, the data using the leave-one-out technique, and a verification set. Consistently, non-parametric discriminant analysis performs as good as or better than the tested alternatives. PMID- 1496191 TI - Analysis of variance for repeated measures. Data: a generalized estimating equations approach. AB - Various techniques are available for the analysis of repeated measures data, and the appropriate choice depends on distributional assumptions and study design features. A correct analysis must account for potential dependence between repeated observations on the same subject. Liang and Zeger proposed a more unified approach to the analysis of repeated measures data based on the application of generalized estimating equations. We examine the application of these methods to several types of data in which one estimates the mean response directly for each combination of discrete covariates, and uses an identity link. Computations for fitting this type of model are exceptionally simple. Numerical examples suggest that the proposed approach yields estimation and hypothesis testing results consistent with more specialized methods. PMID- 1496192 TI - Analysis strategies for serial multivariate ultrasonographic data that are incomplete. AB - Ultrasonographic measurement of intima-media thickness in the carotid artery has emerged as an important non-invasive means of assessing atherosclerosis, and has served to define primary outcome measures related to progression of arterial lesions in several large clinical trials and epidemiologic studies. It is characteristic that measurements often cannot be obtained from all sites during repeated examinations. This leads to incomplete multivariate serial data, for which the set and number of visualized sites may vary across time. We have contrasted several conditional and unconditional maximum likelihood analytical approaches, and have evaluated these with a simulation experiment based on characteristics of ultrasound measurements collected during the course of the Asymptomatic Carotid Artery Plaque Study. We examined analyses based on unweighted and generalized least squares regression in which we estimated cross sectional summary statistics using raw means, unconditional maximum likelihood estimates and full maximum likelihood estimates. Since the genesis of missing data is not fully clear, and since the approaches we examined are based, to some degree, on the assumption that data are missing at random, we also examined the relative impact of deviations from such an assumption on each of the approaches considered. We found that maximum likelihood based approaches increased the expected efficiency of the analysis of serial ultrasound data over ignoring missing data by up to 21 per cent. PMID- 1496193 TI - Comparisons between a new drug and active and placebo controls in an efficacy clinical trial. AB - D'Agostino and Heeren (DH) discussed the multiple comparison issues that arise in evaluating both sensitivity and efficacy in over-the-counter drug trials. We propose a general definition of sensitivity that includes DH's definition as a special case. We also propose a test for sensitivity that coincides with the MIN test of Laska and Meisner at one extreme but has the advantage of identifying specific drugs satisfying the sensitivity criterion when some fail to do so. We suggest that the test of Dunnett as well as an extension of it may be useful for the efficacy comparisons. PMID- 1496194 TI - A method of designing clinical trials for combination drugs. AB - Many pharmaceutical companies are now exploring combination drug therapies as an alternative to monotherapy. Consequently, it is of interest to investigate the simultaneous dose response relationship of two active drugs to select the lowest effective combination. In this paper, we propose a method for designing clinical trials for drug combinations that seems to offer several advantages over the 4 x 3 or even larger factorial studies that have been used to date. In addition, our proposed method provides a convenient formula for calculating the required sample size. PMID- 1496195 TI - Organization and analysis of safety data using a multivariate approach. AB - The collection of safety data is an important part of clinical trials. These safety data are often described and reported in great detail with expenditure of substantial effort and energy. Because of the wide variety of data that require scrutiny from the safety perspective, however, statistical comparisons of the safety profiles of different treatments often lack focus and structure and result in situations where the comparisons for each individual item lack power and thus are inconclusive. In this paper, we propose to organize the safety data into a more manageable form by consolidating them into a number of K classes characterized by body systems and determined in conjunction with the underlying disease as well as the treatments involved. Within each class, we propose assignment to each patient of an overall intensity grade based on all relevant information. The consolidation of the safety data as proposed provides an informative summary for the safety profile of each treatment. The analysis of such organized data concentrates on comparison of the mean intensity grades for different treatments within the K classes simultaneously with use of scores that reflect the acceptability of the various intensity levels to an individual. Furthermore, we demonstrate that the proposed multivariate comparison has much higher power than the univariate one to detect differences in certain cases. We provide examples to illustrate the proposed procedure. PMID- 1496196 TI - Comparing sample size formulae for trials with unbalanced allocation using the logrank test. AB - This paper compares the sample size formulae given by Schoenfeld, Freedman, Hsieh and Shuster for unbalanced designs. Freedman's formula predicts the highest power for the logrank test when the sample size ratio of the two groups equals the reciprocal of the hazard ratio. The other three formulae predict highest powers when sample sizes in the two groups are equal. Results of Monte Carlo simulations performed for the power of the logrank test with various sample size ratios show that the power curve of the logrank test is almost flat between a sample size ratio of one and a sample size ratio close to the reciprocal of the hazard ratio. An equal sample-size allocation may not maximize the power of the logrank test. Monte Carlo simulations also show that, under an exponential model, when the sample size ratio is toward the reciprocal of the hazard ratio, Freedman's formula predicts more accurate powers. Schoenfeld's formula, however, seems best for predicting powers with equal sample size. PMID- 1496197 TI - Sixteen S-squared over D-squared: a relation for crude sample size estimates. AB - I suggest for memorization an equation for calculating approximate sample size requirements intended only for a specific set of values (80 per cent power for a two-tailed alpha = 0.05 test) which seems to occur often in biopharmaceutical research. After presenting the formula in terms of variance estimate s2 and effect size d, I derive a few alternative forms and then discuss the accuracy of the approximation and other properties as well as examples of its use. PMID- 1496198 TI - Sample sizes for proportional hazards survival studies with arbitrary patient entry and loss to follow-up distributions. AB - In proportional hazards survival studies, power depends on the observed number of deaths, d*. For a given choice of survival, loss, and patient entry distributions, sample sizes can be determined by equating d* to the expected number of deaths. Approximating the survival and loss distributions with piecewise exponential distributions, and patient entry with a piecewise linear distribution, significantly reduces the computational overhead, and the expected number of deaths can be evaluated routinely. The merits of this approach are illustrated by a clinical trial of chemotherapy for large bowel cancer. PMID- 1496199 TI - The use of cusums and other techniques in modelling continuous covariates in logistic regression. AB - The assessment of continuous covariates singly as possible predictors in a multivariable logistic regression model is an important first step in the analysis. An approach to plotting which uses a cusum (cumulative sum) of the binary response variable is described. Extreme-deviation statistics associated with the cusum may be used to detect monotonic and non-monotonic trends. Probability plots of the covariate in the two groups defined by the response variable may help to determine the appropriate scale (transformation) of the covariate and to anticipate possible problems with the logistic fit. The ratio of the variances in the response/non-response groups is informative about the need for a quadratic term in the logistic model. Smoothed scatterplots of the response are valuable in displaying the observed and fitted values. The techniques are illustrated with two data sets. PMID- 1496200 TI - Empirical Bayes versus fully Bayesian analysis of geographical variation in disease risk. AB - This paper reviews methods for mapping geographical variation in disease incidence and mortality. Recent results in Bayesian hierarchical modelling of relative risk are discussed. Two approaches to relative risk estimation, along with the related computational procedures, are described and compared. The first is an empirical Bayes approach that uses a technique of penalized log-likelihood maximization; the second approach is fully Bayesian, and uses an innovative stochastic simulation technique called the Gibbs sampler. We chose to map geographical variation in breast cancer and Hodgkin's disease mortality as observed in all the health care districts of Sardinia, to illustrate relevant problems, methods and techniques. PMID- 1496201 TI - [What is your diagnosis? Acute massive retention of the stomach in bulimia]. PMID- 1496202 TI - [Current pathogenetic principles in peptic ulcer]. AB - New concepts in the pathophysiology of peptic ulcers must acknowledge 1. the close association of ulcers and Helicobacter pylori infection, 2. the protective role of endogenous prostaglandins, 3. the scarcity of new data on the importance of acidity (though presence of gastric acid remains indispensible for ulcer development). The different pathophysiologically relevant factors closely interact with each other. However, many not of actual concepts are still experimental and--apart from Helicobacter pylori--have not yet led to new therapeutical approaches. PMID- 1496203 TI - [Therapeutic possibilities in therapy-resistant ulcers--surgical aspects]. AB - Indications for surgery and choice of procedure in complicated or chronic gastroduodenal ulcer refractory to conservative treatment are presented. Operations in emergency states are undisputed although they carry a tenfold higher mortality rate than elective procedures. Therefore in spite of effective pharmacotherapy groups at risk have to be identified by interdisciplinary therapeutic concepts in order to enable elective operation on time. Next to patient and ulcer data the efficacy of various procedures has to be considered. The standardized operative techniques and their associated respective rates of complications and recurrence are compared with those of pharmacotherapy. PMID- 1496204 TI - [Acute ulcer hemorrhage: when to operate--when to wait?]. AB - The identification of prognostic factors in patients with bleeding peptic ulcer is an essential step for improving the outcome. Since recurrence of bleeding is associated with increased mortality, we therefore developed a new treatment policy based on prognostic information identified at emergency endoscopy. Patients with actively bleeding lesions or visible vessel and high risk of recurrent bleeding were operated upon within 6 h (duodenal ulcer) or 24 h (gastric ulcer) even after successful endoscopic control of bleeding. All other patients with oozing type of bleeding or with signs of recent bleeding during emergency endoscopy were primarily treated in a conservative manner. By using this strategy in a prospective trial the overall mortality rate could be markedly reduced from 14 to 5%. PMID- 1496205 TI - [Therapeutic strategy in malignant polyps of the gastrointestinal tract]. AB - Malignant polyps in the stomach are identical with early gastric carcinoma type I and IIa. Even if carcinomatous growth is restricted to the mucosa lymph node, metastases may occur; therefore, local measures like polypectomy or surgical excision are exceptional. Malignant gastric polyps should be treated according to classical tumour surgery. Things are different in malignant colonic polyps, i.e. adenomas with a carcinoma invading the submucosa. Unless one is dealing with a dedifferentiated carcinoma or invasion of lymph or blood vessels is seen a few millimetre of security are sufficient to save the patient from radical surgery. PMID- 1496206 TI - [Chemotherapy in solid tumors of the gastrointestinal tract?]. AB - Chemotherapy in disseminated stages of gastro-intestinal tumor only causes remission rates of 20 to 40% in a reproducible manner. Treatment is clearly palliative and does not influence median time of survival in these patients. In limited stages of esophageal or gastric cancer remission rates above 50% are achieved. However there is no evidence that chemotherapy in addition to surgery improves treatment results. Based on prospectively randomized studies, for stage III colon carcinoma adjuvant chemotherapy using Fluorouracil and Levamisole is recommended. In resected carcinoma of rectum the adjuvant combination of chemotherapy and radiation improves local control of the tumor as well as survival of the patients. This modality of treatment is recommended. PMID- 1496207 TI - [Tumor markers in the diagnosis and therapy of intestinal neoplasms]. AB - Tumor-markers should only be used, if they could alter the management of the patient. Screening for hepatocellular cancer in patients with chronic liver disease and monitoring cancer therapy are established methods. In the future, benign and malignant diseases of the pancreas will become easier to differentiate by the determination of subgroups of Lewis A-antigens. During follow-up after curative surgery, markers are of limited value. Immunoscintigraphy is already in use, whereas therapy with monoclonal antibodies still remains investigational. PMID- 1496208 TI - Prospects in children's neurology in the decade of the brain. PMID- 1496209 TI - [The human face, the most beautiful of scenery]. PMID- 1496210 TI - [Cerebrovascular diseases, 1991]. PMID- 1496211 TI - [Standard electroencephalography mapping in 1992]. PMID- 1496212 TI - [Current concepts in the treatment of status epilepticus]. PMID- 1496213 TI - [Neuroimmunology in Lausanne]. PMID- 1496214 TI - [Current therapeutic possibilities in neurology]. PMID- 1496215 TI - [Movement apraxia]. PMID- 1496216 TI - [Therapeutic approach to the nephrotic syndrome in children]. PMID- 1496218 TI - Locoregional disease control and breast conservation in early breast cancer. PMID- 1496217 TI - [Traumatology of the cervical spine at the general practitioner's office]. PMID- 1496219 TI - The biological significance of locoregional recurrence following breast conserving therapy. AB - Although locoregional recurrence of breast cancer following mastectomy is usually a harbinger of systemic failure, patients experiencing locoregional disease recurrence after breast-conservation therapy enjoy a better prognosis. Tumor recrudescences after a breast-preserving surgical procedure represent both residual tumor and new primary breast carcinomas. Patient prognosis is dependent on the biological characteristics of both the original and recurrent neoplasms. At present, the best predictor of patient outcome is the extent of disease at the times of treatment. While many studies report no statistically significant adverse impact of locoregional recurrence on survival, small sample sizes may obscure such an effect. PMID- 1496220 TI - Multicentricity in early breast cancer. AB - Breast preservation has focused attention on the extent and distribution of cancer in the breast. Recent studies suggest that there is spread from the primary tumor rather than a random distribution of cancer throughout the breast. As a result the term multicentric has largely been replaced by multifocal. Evidence that there is a geographic relationship of secondary deposits to the primary lesions opens the way to wide excision as definative treatment for selected patients with both invasive and in situ breast cancer. PMID- 1496221 TI - Pathologic features related to local recurrence following lumpectomy and irradiation. AB - Breast conservation (lumpectomy and irradiation) has grown increasingly popular as a primary therapy for breast cancer. For the majority of patients whose breast cancers are now being detected at T1N0, both the expected cosmetic result and the survival are excellent. For this reason the possibility of local recurrences in the breast has a disproportionally larger impact on treatment planning for these patients. Although the majority of local recurrences occur in the vicinity of the primary tumor site within the initial 5 years of irradiation, local recurrences can be expected to occur well into the second decade as follow-up is continued. The majority of these late recurrences will not be in the immediate vicinity of the prior excision but represent de novo breast cancers developing in a multicentric fashion in other quadrants. Factors which influence recurrence per se include the size, grade, and stage (nodal status) of the tumor. Such factors influence local, locoregional, and distant metastases. A number of pathologic factors appear to affect only local recurrences. These, including positive margins, gross multicentricity, extensive intraductal carcinoma, and invasive lobular carcinoma, all share a common feature of a greater likelihood of local residual tumor burden. The increased risk of local recurrences related to positive surgical margins and extensive intraductal carcinoma can largely be eliminated by increasing the volume of tissue excised or the radiation dose. In summary, there are no absolute contraindications based on pathologic features of the tumor or the state of the resection margins which should preclude consideration of breast conservation for an individual patient. PMID- 1496222 TI - The pathologist's examination of the "lumpectomy"--the pathologists' view of surgical margins. AB - Despite the widespread conservative management of breast cancer, the pathologists' examination of these specimens is far from uniform. Pathologists sample margins differently, and even disagree on what constitutes a positive margin. This variability in the pathologic examination of the lumpectomy creates tremendous problems in analyzing the existing literature on the importance of positive margins. Herein is a discussion of the available data on the significance of margin assessment. We furthermore suggest a practical approach to examining margins with an emphasis on a functional orientation of the specimen with respect to the nipple. Only by adopting a uniform system of margin assessment can we begin to critically evaluate the importance of positive margins in segmental resections of the breast. PMID- 1496223 TI - Breast-conserving surgery: how much is enough? AB - Breast-conserving operations for the treatment of small, apparently localized invasive breast cancer are now accepted by most surgeons. Still controversial are (1) the size of the primary tumor selected for breast conservation treatment, (2) how much breast tissue must be removed to provide an "adequate" margin to achieve local control, and (3) whether the entire breast needs to be treated by radiation therapy in all patients after adequate partial mastectomy. The results of breast conserving operations at the Cleveland Clinic are presented and the case for selected, individualized therapy utilizing partial mastectomy without radiation therapy for selected patients with small invasive cancers is made. PMID- 1496224 TI - Radiotherapy after breast-conservation surgery: how much is enough? AB - The National Surgical Adjuvant Breast Project (NSABP) clinical trials have demonstrated that breast conservation surgery (lumpectomy), axillary dissection, and breast irradiation for women with Stage I and II invasive breast carcinoma provide disease-free survival and overall survival rates equivalent to modified radical mastectomy. Breast irradiation following lumpectomy decreases the incidence of in-breast tumor recurrence compared to lumpectomy alone. The addition of adjuvant systemic therapy appears to further decrease the incidence of in-breast tumor recurrence. Irradiation of the internal mammary and supraclavicular nodal regions is not indicated for patients with Stage I and II carcinoma. Similarly, irradiation of the axilla after axillary dissection is not indicated. PMID- 1496225 TI - Radiation therapy and breast preservation: past achievements, current results, and future prospects. AB - In this overview the historical development of breast-conserving therapy is sketched briefly from its origins in the second and third decades of this century, and current radiotherapeutic techniques are described. All randomized trials thus far conducted using modern radiotherapy indicate that total mastectomy provides no survival advantage compared with breast-conserving techniques. In patients suitable for such treatment, macroscopically complete local tumor excision followed by appropriate radiotherapy will lead to 90-96% local control in the breast at 5 years, and 81-93% at 10 years. It is likely that the strategy of reserving total mastectomy for treatment of intramammary failures will result in ultimate local control of disease on the chest wall which is superior to that provided by primary total mastectomy. Future prospects include the use of primary chemotherapeutic approaches for larger tumors, extending the possibilities of breast conservation to a majority of patients with tumors classically considered unsuitable for lumpectomy. In this context an increase in the use of radiotherapy in the primary treatment of breast cancer is anticipated. PMID- 1496226 TI - Breast tumor recurrence following lumpectomy with and without breast irradiation: an overview of recent NSABP findings. AB - The latest findings from the NSABP B-06 trial on ipsilateral breast tumor recurrence (IBTR) continue to demonstrate that through 9 years of follow-up more patients treated with radiation remained IBTR free as compared to those receiving no radiation (P less than 0.001), regardless of age, nodal status, or tumor size. There is no significant difference in distant disease-free survival (DDFS) or survival between the two lumpectomy groups despite the highly significant difference in their probability of remaining IBTR free. A recent analysis shows that when a patient is diagnosed with an IBTR, the risk of distant metastatic disease increases, indicating that an IBTR is a marker for, not a cause of, distant metastatic disease. An IBTR indicates a greater risk for distant disease when the primary tumor was removed. Mastectomy or breast irradiation following lumpectomy eliminates or reduces the opportunity for identifying a marker of risk for distant disease, thus emphasizing the importance of an IBTR beyond the need for its removal. Since an IBTR is associated with a relative risk of 3.41 for the development of distant metastatic disease, systemic therapy subsequent to an IBTR should be considered. Evidence presented from recent NSABP studies indicates the value of systemic therapy for lowering the incidence of IBTR following lumpectomy and breast irradiation. PMID- 1496227 TI - Ipsilateral breast tumor recurrence and survival following lumpectomy and irradiation: pathological findings from NSABP protocol B-06. AB - Ipsilateral breast tumor recurrence (IBTR) occurred in 42 of 488 (9%) pathologically evaluable patients enrolled in NSABP protocol B-06 with a mean potential follow-up of 103 months (range 68-161 months) following treatment for Stage I and II invasive breast cancer by lumpectomy and local breast irradiation (LXRT). IBTR were observed at or close to the same quadrant as the index cancers and their histologic types and nuclear grades were similar if not identical in 95 and 93%, respectively. This information confirms our earlier findings which indicated that multicentricity is of little or no clinical significance in the treatment of breast cancer by LXRT; breast cancers rarely if ever change their biologic potential once clinically detected; and lastly, most if not all IBTR represent residual cancer. Cox regression analyses revealed only a patient age less than 35 years to be significantly related to IBTR. No relationship between IBTR and so-called extensive intraductal component (EIC) or 31 other pathologic features of the index cancers was found. Overall survival was significantly related to nodal status (P = 0.01), nuclear grade (P = less than 0.001) histologic tumor type (P = 0.01) and IBTR (P = less than 0.001). This latter was considered as an indicator rather than instigator of distant disease and reduced survival since the latter is no different in patients treated by LXRT, lumpectomy alone after which IBTR is much more frequent, or mastectomy, which precludes its expression. We conclude that there are as yet no viable markers which would contraindicate treating patients with breast cancer by LXRT. PMID- 1496228 TI - Breast-conserving surgery and selective adjuvant radiation therapy for stage I and II breast cancer. AB - In this report we update our experience with selective adjuvant radiotherapy (XRT) following breast-conserving surgery (BCS) for early breast cancer. Of 150 evaluable private breast cancer patients treated by BCS since 1975, 83 were offered the option of foregoing adjuvant XRT because their primary disease met four pathological criteria: primary tumor less than or equal to 2.5 cm; adequate resection margins; no intramammary vascular, lymphatic, or perineural invasion by tumor; and minimal or no associated in situ cancer. Of the 67 patients who chose not to have XRT, four have developed local (breast) tumour recurrence at 80 months' median follow-up (5-year local recurrence rate 6.4% by Kaplan-Meier analysis). These findings are discussed in light of other series in which patients were carefully selected for BCS without XRT, and the observations of large randomized trials and unselected series of patients. We conclude that adjuvant XRT is not always necessary following BCS. The most valuable contribution of XRT to breast-conserving therapy is that a much larger proportion of breast cancer patients can be considered for conservative locoregional surgery than would otherwise be reasonable. PMID- 1496229 TI - [Impact of the Free Trade Agreement on the clinical laboratory and Mexican medicine (2)]. PMID- 1496230 TI - [Prevalence of asthma. Survey of a school population in Villahermosa, Tabasco, Mexico]. AB - In the state of Tabasco, Mexico, there apparently exists a great demand for medical care in children with asthma, yet the exact number of children with this illness is unknown. This motivated us to survey the parents of 5,625 school children with ages ranging from 6 to 12 years old (2,386 girls and 2,789 boys) living in the city of Villahermosa, Tabasco. The study included 11% of the school children in the vicinity. The survey showed that 22.3% of the population of school children refer chronic or repetitive respiratory symptoms; 8.7% referred a diagnosis of asthma; 6.8% bronchitis; 2.3% asthmatic form bronchitis; and 3.9% symptoms suggestive of repeated bronchial obstruction. PMID- 1496232 TI - [Immunotherapy of type 1 diabetes]. AB - Insulin-dependent diabetes mellitus is the late consequence of a chronic autoimmune disease directed to the B islet cell, that begins long before the hyperglycemic state. Experimental evidence suggests a central pathogenic role for autoreactive T lymphocytes. Immunointervention studies, particularly those using cyclosporin, have shown that it is possible to stop B cell destruction, even at the late stage of overt diabetes. New therapeutic approaches will be focused on the use of specific agents such as monoclonal antibodies and immunotoxins, and on earlier interventions allowed by the detection of genetic and immunological markers of prediabetes. PMID- 1496231 TI - [Allergenic flora in the valley of Mexico. Relation with food sensitivity of vegetable origin (4)]. PMID- 1496233 TI - [Screening and prevention of type 1 diabetes]. AB - Insulin-dependent diabetes mellitus is preceded by a prodromal phase during which insulin-secreting cells are progressively destroyed by immunological factors. Among genetically predisposed and high risk subjects, this phase of prediabetes can be identified by detection of immunological and metabolic markers. For these prediabetic subjects, specific immunomodulators, without adverse effect, will be available. PMID- 1496234 TI - [Administration of insulin in type 1 diabetes]. AB - Insulin therapy by subcutaneous injection is not satisfactory: it rarely brings down glycaemia to its normal level, exposes to the risk of hypoglycaemia and hyperinsulinism, is difficult to endure for a long period and requires full patient's involvement. Improvements are being achieved in the route of insulin administration (intraperitoneal and nasal routes), the type of insulin (analogues) and the material used to administer the hormone (insulin pens and implantable pumps). PMID- 1496235 TI - [Islets of Langerhans grafts and pancreas transplantation]. AB - In theory, transplantation of the islets of Langerhans is the method of choice for the treatment of insulin-dependent diabetes. In actual fact, medical teams who have been working on this subject for about two decades have met with the problem of islet isolation, and for the time being this treatment cannot be considered effective. Pancreas transplantation gives satisfactory results in diabetics with renal impairment when it is coupled with kidney transplantation. However, it cannot yet be applied to all diabetics as its results are mediocre when performed alone, and it requires chronic immunosuppression. Pancreas transplantation not only increases the quality of life but also has the advantage of acting on degenerative complications: it may improve diabetic nephropathy, retinopathy and neuropathy. The results obtained are getting better year after year, and they are now close to those observed with other organ transplantations. PMID- 1496236 TI - [Oral and dietary treatments of type 2 diabetes]. AB - Non insulin-dependent diabetes mellitus requires a metabolic and vascular treatment in order to prevent macroangiopathy. Personal diet management, which is similar in diabetic and non diabetic comparable patients, is the basis of therapy. Any significant result cannot be expected without its observance. Sulfonylurea and biguanide drugs can enhance diet action and must be prescribed secondarily according to the level of hyperglycaemia. Blood pressure and lipid control is as important as glycaemic normalization. Early diet management of obese people should be the best approach to prevent type II diabetes. PMID- 1496237 TI - [Insulin in type 2 diabetes. Why, when, how?]. AB - Non insulin-dependent diabetes is often associated with obesity and always with some degree of insulin resistance. First choice treatment consists of appropriate and sometimes hypocaloric diet and oral hypoglycemic agents. Using insulin becomes mandatory in patients with associated pathology or at risk of metabolic imbalance. Insulin administration must be discussed in each individual case when it aims at a long-term improvement of blood glucose control, taking into account the lack of consensus on this point and the potential drawbacks of insulin therapy, notably weight increase and risk of hypoglycaemia. PMID- 1496238 TI - [Diabetes in elderly subjects]. AB - Problems raised by diabetes in subjects above 65 years of age are of three kinds: diagnostic, therapeutic and social. Passed the age of 40, there is a regular physiological increase of glycaemia, and this must be taken into account to diagnose diabetes and to set the threshold for therapeutic intervention. The treatment of elderly people has its specific imperatives, due to feeding habits and age-related changes in hepatic and renal functions. The presence of complications, sometimes multiple, explains that the patient often takes several drugs, which increases the risk of interaction between these drugs and oral antidiabetics. The therapeutic objectives must be adjusted to these imperatives, and neither the diabetic... nor his doctor must be afraid of insulin. The social status of elderly patients must not be neglected: the help of private nurses and the training in diabetology of the patient's entourage often permit to postpone the date of institutionalization. PMID- 1496239 TI - [Treatments of diabetes in children]. AB - The treatment of children with type I insulin dependent diabetes mellitus has been improved by the combination of multi-daily self blood glucose monitoring and insulin injections. Specific aspects of therapy in neonatal diabetes, as well as in infants, are discussed. Non insulin dependent diabetes is rarely observed in pediatric ages and is generally treated with simple diet control. PMID- 1496240 TI - [Diabetes education]. AB - Diabetes is a chronic disease requiring a compelling and permanent treatment which has repercussions on the patient's daily activities, tempo of life, feeding habits and physical exercises. This treatment also carries a risk of acute metabolic complications dreaded by the patient, the main one being hypoglycaemia. These constraints and fears have important effects on the patient's state of mind and must be taken into consideration by all those who look after him. For a strict and global handling of the diabetics' medical problems, it has been found necessary to institute an educational approach aimed at informing the patient, teaching him practical actions, facilitating his autonomy and reducing his anxiety and isolation. This approach is called diabetes education. It requires special training, as well as time and means, and must be subjected to evaluation. It is now well established that diabetes education is able to reduce the constraints of the disease, the frequency of metabolic accidents and the cost of diabetes. It is usually developed in hospital structures, but it also concerns private diabetologists and other medical helpers. This should convince the State authorities to recognize this teaching activity as a genuine therapeutic activity. PMID- 1496241 TI - [Keratoprosthesis. Artificial cornea]. PMID- 1496242 TI - [Angiography by magnetic resonance. Increased indications in neuroradiology]. PMID- 1496243 TI - [Medico-legal activity in a hospital setting. A hospital specialty in itself]. PMID- 1496244 TI - [History of hemodialysis in acute uremia]. PMID- 1496245 TI - [Hypoglycemia. Diagnostic orientation and treatment]. PMID- 1496246 TI - [Digestive hemorrhages. Diagnostic orientation and emergency treatment]. PMID- 1496247 TI - [Hyperhydration. Etiology, physiopathology, diagnosis, principles of treatment]. PMID- 1496248 TI - [Non-steroidal anti-inflammatory agents. Principles and rules of their utilization]. PMID- 1496249 TI - [Epilepsy in children and in adults. Etiology, diagnosis, development, prognosis, principles of the treatment]. PMID- 1496250 TI - [Myocardial infarction. Physiopathology, diagnosis, development and prognosis, treatment]. PMID- 1496251 TI - [Visual field abnormality. Diagnostic orientation]. PMID- 1496252 TI - [Leukocyturia-bacteriuria. Diagnostic orientation]. PMID- 1496253 TI - Study on the prevalence of eccentric and concentric atherosclerotic plaques in various segments of the coronary arterial tree, in unselected and selected Bucharest population samples. AB - A study was carried out on the prevalence and distribution of eccentric and concentric atherosclerotic plaques in the coronary arterial tree of 916 unselected apparently healthy subjects who died from accidents and of 150 selected patients who died from coronary heart disease. The results show that the percentages of eccentric and concentric plaques vary with age, sex, anatomical branching pattern and cause of death; there are also differences between major coronary arteries and main branch vessels. In addition to eccentric and concentric plaques, we revealed the existence of mixed (both eccentric and concentric) plaques, mainly located at branch points. PMID- 1496254 TI - [The determination of ventricular late potentials by temporospatial spectral analysis in post-myocardial infarct patients]. PMID- 1496255 TI - [Tuberculosis and mycobacterioses in HIV infection]. PMID- 1496257 TI - Incidence and evolutive tendency of intestinal metaplasia in chronic gastritis. AB - The histologic examination of 556 gastric biopsies performed in patients with chronic gastritis, revealed the presence of intestinal metaplasia in 81 cases (14.5%). This was correlated with the evolutive stage of gastritis, the maximum incidence being observed in the case of gastric atrophy (24.7%). The iterative examination of the patients with intestinal metaplasia, allowed the determination of its evolutive tendency. After an average period of 5 years, the occurrence of gastric malignoma was observed in 5 cases (6.3%) thus confirming the oncogenic risk of intestinal metaplasia and justifying the careful "surveillance" of these cases. PMID- 1496256 TI - Transesophageal determination of SNRT and SACT in paroxysmal supraventricular tachyarrhythmias. AB - The paper tested the hypothesis that supraventricular tachyarrhythmias (SVT) could represent the first clinical manifestation of the sick sinus syndrome (SSS). Absolute sinus node recovery time (SNRT) and sinoatrial conduction time (SACT) were determined through transesophageal approach in 16 patients with paroxysmal SVT, but without bradycardic episodes between crises. The values considered normal were: SNRTa less than or equal to less than or equal to 1500 ms; SNRTc less than or equal to 525 ms; SACT less than or equal to 150 ms. SNRTa, SNRTc and SACT were normal in all subjects (SNRTa: 1077 ms; SNRTc: 400 ms; SACT: 111 ms) and suggest the absence of a notable sinusal disfunction in these patients. We concluded that SVT unassociated with bradycardia do not usually represent a manifestation of SSS. Consequently the administration of sinusal depressant drugs in such patients could be permitted without restrictions. PMID- 1496258 TI - Comparative study of the variations of the phagocytic capacity of polymorphonuclear leukocytes and of total plasma antioxidants in patients with pneumoconioses and lung cancer. AB - A comparative, preliminary study of the phagocytic capacity of polymorphonuclear leukocytes, and of the total plasma antioxidants was carried out in a group of workers professionally exposed to mineral dusts and in a group of patients with lung cancer. Both groups exhibited advanced respiratory failure stages II and III. The phagocytic capacity of polymorphonuclear leukocytes was found significantly increased in workers with pneumoconioses and moderately increased in patients with lung cancer. On the other hand, the peroxides and total plasma antioxidants exhibited great individual variations. Thus in lung cancer it was observed that peroxides had a tendency to decrease and antioxidants to increase. The individual study of the variations of these three parameters might be able to differentiate the reversible from the irreversible stages of the respiratory changes. PMID- 1496259 TI - Changes of circulating immune complexes in the serum and CSF of patients with multiple sclerosis. AB - The level of circulating immune complexes (CIC) was studied before and after treatment in a group of 86 patients with multiple sclerosis (MS) (36 males and 50 females) ranging in age between 20 and 30 years and in 32 controls. CIC determinations were performed both in the serum and in the CSF, using the method of precipitation in polyethylene glycol (PEG). In 61.62% of the patients the mean serum CIC values (82.44 ODU; p = 0.01) exceeded those found in the controls (60.1 ODU) while the CSF mean CIC values (21.63 ODU; p = 0.05) exceeded those in the controls in 59.30% of the patients (12.8 ODU). The prevalence of patients with CIC values exceeding the control values presented variations according to the clinical stage of disease. Thus in the acute stage 83.33% of the patients presented the highest mean serum CIC values (110.5 ODU; p = 0.05) and 100% of the patients presented the highest mean CSF CIC values (27.9 ODU). After treatment it was observed that the prevalence of patients with high CIC values decreased. In conclusion it was observed that there is a correlation between the prevalence of patients with increased CIC values in the serum and CSF, and the clinical stage and treatment administered. This observation suggests that CIC determinations both in the serum and in the CSF may constitute an immunologic marker in MS. PMID- 1496260 TI - The variations of the serum IgD and of the circulant immune complexes in diabetic patients. AB - The levels of serum IgD and of the circulating immune complexes (CIC) were determined in 168 diabetic patients, of whom 78 with type 1, 59 with type 2 and 31 with the so-called "intermediary" type of the disease, in comparison with 124 non-diabetic subjects for IgD and 100 for CIC. The results revealed very low IgD titres (less than 1 mg%, considered undetectable) in almost 3/4 of the cases; values over 1 mg% were recorded mostly in the cases of type 1, followed by those of "intermediary" and of type 2 diabetes. The mean CIC values of 67.13 +/- 36.53 optic density units (O.D.U.) were significantly higher than in the non-diabetic controls. Certain differences with respect to age, diabetes type, duration of the disease and of the insulin therapy were also recorded. The data are interpreted with caution, further investigations being necessary to the assertion of definite conclusions. PMID- 1496261 TI - The in vitro action of a succussed substance on the proliferative response of human lymphocytes stimulated with phytohemagglutinin. AB - Human peripheral blood lymphocytes from healthy controls, immunodepressed patients presenting chronic bacterial infections or neoplasias and from allergic patients were stimulated in vitro with phytohemagglutinin (PHA) in culture medium supplemented or not with 1 x 10(-7), 1 x 10(-15) or 1 x 10(-30) succussed dilutions or bee venom or phosphorus in tridistilled water. The most significant inhibition due to DNA incorporation was noted in lymphocytes from allergic patients cultivated in media supplemented with 1 x 10(-30) succussed substance dilution in the presence of PHA. The cells from immunodepressed patients did not show a significant inhibition at 1 x 10(-30) dilution. Hypothetically, we try to explain these findings as the expression of the changes induced by the succussed solution on the water molecule which in turn, influences the chemical structure of the cellular membrane and implicitly, its functions. PMID- 1496262 TI - Heterozygous protein C deficiency and coumarin necrosis of the skin. AB - An obese female patient aged 47 with a personal and familial history of recurrent venous thrombosis, who developed a coumarin-induced skin necrosis is presented. Laboratory investigations, performed three months after the acute event and in absence of coumarin therapy, emphasized a decreased anticoagulant activity of her plasma protein C (50% of the normal). These results as well as the high incidence of thrombotic disease in her relatives point to a familial heterozygous protein C deficiency. The antithrombotic role of the protein C system and the mechanism of coumarin induced necrosis of the skin are briefly discussed. PMID- 1496263 TI - The changes of peroxides and total antioxidants in the plasma of patients who received 131I therapeutically. AB - Fifty patients with thyroid cancer were studied during administration of high doses of 131I (5-50 mCi). Peroxides, total antioxidants and free sulphydryl groups were measured in the blood samples obtained before and after administration of radioactive iodine. After the administration of iodine, significant increases of peroxides and free SH groups were observed, as well as the decrease of total antioxidants. These biochemical changes were in agreement with significant decreases of blood platelets and lymphocytes. The data obtained brought forward again the much debated problem of peroxidation and antioxidants in cancer, since comparatively, the patients with other localizations of tumors presented decreases of peroxides and variable amounts of antioxidants. The influence of iodine and thyroid hormones is discussed, with reference to a previous paper in which high levels of peroxides had been found both in hyper- and in hypothyroidism but with different mechanisms. The biochemical changes observed in the patients treated with radioactive iodine confirmed the involvement of peroxides in the consequences of internal irradiation. PMID- 1496264 TI - Circulating immune complexes and the complements system in lupus nephropathy. AB - From a group of 75 patients with systemic lupus erythematosus (SLE), 30 patients with lupus nephropathy presenting concomitant changes of the CIC level, of the complement system (C3 and C1q factors) and proteinuria were chosen for the study. In these 30 patients, no statistically significant correlation was observed between CIC level and the value of serum complement. Low serum complement was observed in 89% of the cases while low complement values associated with increases of the CIC level were observed only in 57.8% of the cases. From the values of the C3 and C1 complement factors it results that in 76.6% of the cases of lupus nephropathy the activation of complement was achieved in the classical way. The value of proteinuria presented no significant correlation with any of the parameters investigated. The serum immunogram presented varied aspects and the components of the CIC structure revealed a great diversity of this structure. PMID- 1496265 TI - Echographic diagnosis of cardiac involvement in systemic lupus erythematosus and systemic scleroderma. AB - The great frequency and severity of cardiac involvement in collagen diseases have proved to be an important diagnostic, prognostic and therapeutic problem. In the last few years the value of echographic examination in the estimation of the pathologic cardiac changes in the course of systemic lupus erythematosus (SLE) and of systemic scleroderma (SS) has considerably increased making the object of numerous studies. In this paper the results obtained in some of these studies are estimated comparatively. PMID- 1496266 TI - [The characterization of focal hepatic lesions by color-coded Doppler echography. A preliminary test]. PMID- 1496267 TI - [Ventricular late potentials studied by high-amplitude electrocardiography in relation to the length of the QT interval]. PMID- 1496268 TI - Comparative value of arm and leg exercise testing. AB - Arm exercise test (AET) is described as an alternative to the classical leg exercise test (LET). The value of these two types of exercise was studied in a group of 32 patients aged 34 to 65 years. The patients performed LET for several reasons and, after 24 hrs, AET under the same conditions. The effort level reached under LET was always greater than that achieved under AET and the calculated functional aerobic impairment (FAI) was 50% greater during AET thus supporting the idea that AET cannot be used instead of LET in determining the functional capacity (NYHA) of cardiac patients. However, AET remains useful for the determination of the occupational working capacity in certain occupational categories. The double product (DP) (or index tension time (ITT) calculated after AET represented 85% of the calculated value after LET. The results proved that MVO2 is similar for both LET and AET, but in the latter at lower levels of exercise (VO2). The LET-DP was greater than the AET-DP in 66.5% of our cases, thus suggesting that AET should be reserved for situations in which LET cannot be performed. This is also supported by the presence of ST depression during AET in only 66% of the 18 subjects with ST depression during LET and in five of the six patients without ST depression, DP-AET was lower than DP-LET. PMID- 1496269 TI - [Parathyroid-related protein (PTH-rP): from humoral hypercalcemia to physiological hormone]. PMID- 1496270 TI - [Fracture of the upper extremity of the femur in elderly women: respective role of fall and bone demineralization]. AB - Fractures of the proximal femur in elderly individuals are becoming increasingly common in the industrialized world and represent a heavy burden in both socioeconomic and human terms. Two factors are key to the pathophysiology of these fractures: falls and decreased bone strength due to osteoporosis. Femoral and vertebral bone density was measured in 40 elderly women (83 +/- 5 years) who experienced a fall; in those who developed a femoral fracture as a result of the fall, femoral bone density was lower by 12 to 21% (z score: -0.7 to -1.04) than in those with no fracture, after adjustment for age, height and weight. Femoral neck and trochanteric area measurements had the best predictive value (area under the RoC curve: 75% +/- 8%). These was no difference by anatomic fracture type (neck or trochanter). Patients with pertrochanteric fractures had lower vertebral bone densities than controls. These findings, together with recent prospective data, demonstrate that in addition to falls, bone loss (osteoporosis) promotes the occurrence of fractures of the proximal femur in elderly patients. This has important practical implications for the detection and prevention of these fractures. PMID- 1496271 TI - [Bone density in differentiated cancer of the thyroid gland treated by hormone suppressive therapy. Study based on 51 cases]. AB - The effect of L-Thyroxine suppressive therapy (207.3 +/- 46.1 mcg/d) on lumbar spine bone density (BMD) was assessed in 51 patients thyroidectomized for carcinoma since 1 to 19 years (mean = 6 +/- 5.4 years); the bone densities of these patients were compared with those of 51 age sex weight-matched control subjects. Trabecular bone density was evaluated by single energy quantitative tomography. The vertebral BMD was not significantly different between the patients receiving suppressive doses of L-T4 and the control group (162.8 +/- 40.4 vs 162.7 +/- 39.8 mg/cm3). We found no relationship between the duration of L-Thyroxine therapy and BMD. Thus, doses of L-T4 sufficient for suppressing plasma thyroid stimulating hormone but no high enough for causing biochemical thyrotoxicosis have no harmful effect on trabecular bone mineral density. PMID- 1496272 TI - [Erythromelalgia in adults. Apropos of 16 cases]. AB - The authors report sixteen consecutive cases of erythromelalgia, an infrequent disease in which local heat, redness, and pain develop in the hands and/or feet in recurrent attacks. The disease was essential in nine patients; in the remaining seven, the cause was a myeloproliferative syndrome (polycythemia vera in 3 cases and thrombocythemia in 1 case) or a drug (bromocriptine, nicardipine, and nifedipine, one case each). Acetylsalicylic acid was effective in only six of the nine essential cases. Intravascular platelet activation and aggregation with plugging of the arterioles has been suggested as the mechanism of erythromelalgia in patients with myeloproliferative disorders. Other, as yet unelucidated pathophysiologic events underlie the juvenile-onset forms, which usually fail to respond to acetylsalicylic acid. PMID- 1496273 TI - [Report of the General Secretary on the activities in 1991 (presented January 1992)]. PMID- 1496274 TI - [Mode of action of non-narcotic analgesics]. AB - According to Lim's experiments, non-narcotic analgesics are usually considered as "peripherally" acting drugs. Conversely, most of these compounds were shown to easily cross the blood-brain barrier, and hence partly produce their effects by a central mechanism. The relative contribution of each site of action may vary from one drug to another. Aspirin-like drugs may act by inhibiting arachidonate cyclooxygenase in both the damaged tissues and the central nervous system. Finally, these drugs appear to be either selective, or dose-dependent, or nonspecific inhibitors of prostaglandin-synthetases. PMID- 1496275 TI - [Post-traumatic osteoid osteoma. Apropos of 2 cases and review of the literature]. AB - Two cases of osteoid osteoma which became clinically apparent after a prolonged silent period are reported. One was located in the tibia in a 30-year-old female and the other in the femur in a 26-year-old male. Both developed after a surgical procedure, at the site of the operation; one was located on the track of an internal fixation screw. Diagnosis was delayed despite the suggestive timing of the pain; isotopic scanning, CT scan and angiography provided suggestive data and diagnosis was confirmed by histologic studies. A review of the literature found 13 other cases meeting the following criteria: initial trauma, silent period, suggestive pain, discovery of an osteoid osteoma at the site of the trauma, and recovery following surgical treatment. The role of the trauma is discussed. PMID- 1496276 TI - [Pseudo-eventration: unusual complication of vertebral osteoporotic compression]. AB - A new case of neurological complication of an osteoporotic vertebral fracture is reported. Authors emphasize electromyography which explained the clinical presentation of pseudo-evisceration by showing an injury of the 12th spinal nerve. To their knowledge, this kind of complication was never reported before, but they think that the development of electromyographic practice would allow to find many others cases. Authors emphasize MRI which gives strong argument for osteoporotic nature of a vertebral fracture and could avoid having recourse to vertebral biopsy. PMID- 1496277 TI - [Rhabdomyolysis due to simvastin. Apropos of a case with review of the literature]. AB - A new case of simvastatin-induced acute rhabdomyolysis with heart failure after initiation of treatment with fusidic acid is reported. In most reported instances, statin treatment was initially well tolerated with muscle toxicity developing only after addition of another drug. The mechanism of this muscle toxicity is unelucidated but involvement of a decrease in tissue Co enzyme Q is strongly suspected. PMID- 1496278 TI - [Efficiency of cyclophosphamide bolus in Still's disease in adults. A case]. AB - The value of monthly intravenous injections of cyclophosphamide in adults with steroid-dependent Still's disease is documented by the report of a case. In the short term and perhaps also in the long term, this regimen reduces the amount of prednisone needed. PMID- 1496279 TI - [Systemic urticaria, sclerosing osteopathy, monoclonal gammopathy (Schnitzler syndrome). Apropos of a case]. AB - A 65 years old man has been suffering from the upper limbs and legs for 2 years. Bone pain was associated with a non pruritic chronic urticaria and fever. Bone scintigraphy showed lesions of the lower limbs. X rays showed only one sclerotic bone lesion. Immunoelectrophoretic analysis showed an IgM kappa monoclonal gammapathy. Bone marrow aspirate and bone marrow biopsy were normal. The association of chronic urticaria, bone pain and macroglobulinemia has been first reported by L. Schnitzler. Seventeen other cases have been reported in the literature. The pathogenesis of the syndrome is unknown although anti-interleukin 1 alpha autoantibodies were found in several cases (8 out of 13). PMID- 1496281 TI - [Peri-ungueal capillaroscopy. A new simple inexpensive method]. PMID- 1496280 TI - [Gougerot-Sjogren syndrome associated with dysthyroidism. Development of histological lesions in the salivary glands following treatment for dysthyroidism]. PMID- 1496282 TI - [Does the histodynamic aspect of common osteoporosis depend of geographic factors?]. PMID- 1496283 TI - [Extensive algodystrophy of lower limbs associated with bronchial cancer]. PMID- 1496284 TI - [Tendon rupture and fluoro-quinolones: an undesirable effect of drug selection]. PMID- 1496285 TI - [Alcaptonuric rheumatism. A case followed for thirteen years]. PMID- 1496286 TI - Continent Urinary Reconstruction. Proceedings and abstracts of 1st International Meeting. Lund, Sweden, June 10-12, 1992. PMID- 1496287 TI - Bladder substitutes made of crossfolded ileum. PMID- 1496288 TI - Bladder replacement by colon. PMID- 1496289 TI - Total vesicourethral replacement in the female--the case for artificial sphincter around bowel. PMID- 1496290 TI - Total pelvic exenteration with simultaneous bowel and urinary reconstruction. PMID- 1496291 TI - The prosthetic bladder--perhaps the technology has arrived. PMID- 1496292 TI - Indications for and evaluation of patients for enterocystoplasty. PMID- 1496293 TI - Techniques and complications of substitution and augmentation cystoplasties. AB - Techniques of achieving a docile lower urinary tract and continence mechanisms using bowel segments have improved unmeasurably over the last decade. The medium term complications are well documented. The long term problems of chronic infection are being addressed but it remains to be seen whether tumour formation occurs eventually in some patients and whether renal function is better preserved by a continent reconstruction rather than a surface diversion. PMID- 1496294 TI - Thoughts on urinary undiversion. PMID- 1496295 TI - Lower urinary reconstruction in patients with severely impaired renal function. AB - With the current techniques available for reconstruction no patient should be transplanted into a surface diversion. Although rigorous follow-up of patients with vesicourethral dysfunction should prevent renal failure occurring, such patients continue to appear. Both groups require reconstruction before transplantation preferably before end stage renal failure is reached since healing is better and the problems of the dry bladder reconstruction avoided. The results from this multidisciplinary group have been rewarding. PMID- 1496296 TI - Continent urinary reconstruction and reproductive function. PMID- 1496297 TI - Current trends and possible future developments in continent urinary reconstruction. PMID- 1496298 TI - Surgery, cancer and quality of life: ethical aspects. PMID- 1496299 TI - Intestinal motility and its disorders. PMID- 1496300 TI - Metabolic effects caused by exclusion of intestinal segments. PMID- 1496301 TI - Morphologic changes of intestinal mucosa in contact with urine. PMID- 1496302 TI - Electrolyte abnormalities as a consequence of urinary intestinal diversion. PMID- 1496303 TI - Electrolyte transport in gastric mucosa in contact with urine. PMID- 1496304 TI - Dynamic characteristics of intact and detubularized bowel segments for continent urinary reconstruction. PMID- 1496305 TI - Bladder replacement using ileocaecal tract with taeniomyotomies of the caecal segment to reduce intraluminal pressure. PMID- 1496306 TI - Bacterial adherence and mucosal inflammation in the bowel and the urinary tract. PMID- 1496307 TI - Kidney function in bladder substitution. PMID- 1496308 TI - Problem of secondary malignancy after urinary diversion and enterocystoplasty. PMID- 1496309 TI - Indications and contraindications for continent urinary diversion. PMID- 1496310 TI - Intussuscepted ileal nipple valve--early experience. PMID- 1496311 TI - Intussuscepted ileal nipple valve--development and present status. PMID- 1496312 TI - Hydraulic valve for continence and antireflux. A 17-year experience of 210 cases. AB - The hydraulic ileal valve ensures urinary continence and can be employed in many different reservoirs. The valve is constructed by isolating a 14 cm long intestinal loop with its mesentery. The isolated ileal segment is then folded inward on itself throughout its length. This hydraulic valve was used in the construction of 210 continent urostomies--ileocaecal reservoir in 184 cases (including 8 detubularized), ileal reservoir in 15, sigmoid in three, rectum and transverse colon one each, and bladder (continent cystostomy) in six cases. The indications for continent urostomy included bladder tumour (45.5% of cases), complex vesicovaginal fistula (31%), neurogenic bladder (11%) and bladder exstrophy (7%). Continence was immediately achieved in 155 patients (75%), rising to 91.5% after valve repair. The mean postoperative follow-up was 56 (range 3 205) months. PMID- 1496313 TI - The plicated or tapered ileal outlet--"Indiana pouch". PMID- 1496314 TI - Appendix as continent urinary reservoir outlet. AB - The submucosally embedded in situ appendix offers an ideal continence mechanism in patients with ileocaecal urinary reservoir. Ninety-two patients who underwent this procedure at three urology centres (48 patients in Mainz, 20 in Wuppertal Barmen and 24 in Marburg) are reviewed. The appendicocutaneous stoma was placed in the lower right abdominal quadrant in 12 patients (most of whom previously had bladder exstrophy) and into an umbilical or, in some exstrophy cases, a neoumbilical tunnel in 80 patients. Urodynamic investigations of the submucosally embedded appendix showed maximum closure pressure greater than 80 cm H2O. PMID- 1496315 TI - The appendix as a continent conduit. PMID- 1496316 TI - The Kock pouch for continent urinary reconstruction focusing on the afferent segment and the reservoir. PMID- 1496317 TI - The Mainz pouch. PMID- 1496318 TI - The right colonic segment as reservoir for urine. PMID- 1496319 TI - Continent urinary diversion in childhood: European experience. PMID- 1496320 TI - Continent urinary diversion in children: the American experience. PMID- 1496321 TI - Ureterosigmoidostomy: past, present and future. PMID- 1496322 TI - The modified rectal bladder: a bladder substitute controlled by the anal sphincter. PMID- 1496323 TI - The valved S-shaped rectosigmoid pouch for urinary diversion. PMID- 1496324 TI - The risk of urethral recurrence after radical cystectomy. PMID- 1496325 TI - Continence mechanisms following orthotopic bladder substitution. PMID- 1496326 TI - Surgical technique for cystoprostatectomy prior to bladder substitution. PMID- 1496327 TI - The ileal neobladder: development and long-term experience, Camey I and II. PMID- 1496328 TI - Condom use due to the risk of AIDS. Trends in the general population of Sweden. AB - This study examines the use of condoms due to the risk of AIDS in the general population of Sweden during 1986-1989. The study is based on annual mail surveys (1986-1989) of random population samples aged 16-44 years - 4000 individuals in each sample. The response rate was 71%. The study indicates that the use of condoms increased significantly during the first years of the study period, particularly among 18-24-year-olds. Roughly the same tendency was observed regarding the perception of personal risk related to HIV infection. In 1988 a positive connection was established between condom use and personal risk perception. Between 1988 and 1989 (as the public interest in the AIDS issue declined) no further increase in condom use was observed but rather a tendency of reversal towards previous levels. Having several sexual partners was not significantly associated with a more frequent use of condoms, nor was the occurrence of casual sexual contacts. In most of the casual sexual contacts reported condoms were not used. PMID- 1496329 TI - Waiting time to pregnancy and pregnancy outcome among Danish workers in the textile, clothing, and footwear industries. AB - The relationship between time from planned to achieved pregnancy and pregnancy outcome has been studied in a group of 18,658 workers in the textile, clothing and footwear industries. Information on pregnancy outcome and delay in conception in the period 1979-84 was collected by self administered questionnaires in 1985. The response rate was 70.3%. During the study period there had been 5,171 live births and 708 spontaneous abortions. Information on delay in conception was collected in broad categories. The data were analysed by means of a newly developed statistical parametric model in order to collect all possible information from the highly grouped data. Median waiting time before a pregnancy which ended in spontaneous abortion was 1.68 times longer than median waiting time before a pregnancy leading to a live birth. There seems to be a correlation between the length of the waiting time and abortion. PMID- 1496330 TI - Nurses' attitudes towards shiftwork and quality of life. AB - The repercussions on the social and family life of shiftworkers are important. The objectives of this work are to compare the attitudes to permanent and rotating shiftwork, and the impact of shiftwork on social and family life. A cross-sectional epidemiological study was carried out in 606 female and 367 male nurses chosen at random from public hospitals in the Valencian region. Information was gathered by means of a questionnaire, and descriptive analysis was carried out. It can be concluded that workers on rotating shifts who are dissatisfied with their working hours give incompatibility with social and family life as the main reason. Furthermore, working nights (permanently or rotating) disturbs harmony between working hours and days off of the spouse. PMID- 1496331 TI - Feasibility of a 2-km walking test for fitness assessment in a population study. AB - A simple 2-km Walking Test has been developed for determining the cardiorespiratory fitness of healthy adults. In the present study the following aspects of the feasibility of this test for population assessment were investigated: participation willingness, the percentage of test qualified subjects, the percentage of acceptable test performances and the resources needed for field test administration. A representative sample was drawn from the 27 to 65-year-old population in a rural municipality in northeastern Finland. Subjects were recruited on the basis of the results of health questionnaires and interviews. One fourth of the volunteers were excluded from the test because of health problems. The 2-km walking tests were administered outdoors in the municipality center. More than 50% of the subjects successfully completed two consecutive walking tests. This study indicated that the 2-km Walking Test is a feasible alternative as a measure of cardiovascular fitness for large population groups and could potentially be used in exercise related health promotion programmes. PMID- 1496332 TI - Suicide among young people aged 10-29 in Sweden. AB - This study analyses the incidence of suicide among children and young people aged between 10 and 29 in Sweden, during the period 1974-1986. The study comprises 4,624 individuals whose deaths were the outcome of verified, E950-E959 (n = 3,511) and undetermined, E980-E989 (n = 1,113) suicides. Regression analysis of different age groups separately and all age groups combined shows that the frequency of suicide among children and young people in Sweden did not increase in this period. Nonetheless, mortality figures are high, especially for boys and young men aged 15-29. The maximum suicide-mortality rate (43.2 per 10,000) is noted for young men aged 25-29 in 1984. The male-female ratio with respect to deaths from suicide is 2.5 for the entire group, the smallest difference being in the 15-19 age group (1.7) and the largest in the 25-29 age group (2.8). Methods of committing suicide vary between the sexes and the various age groups. Boys and young men use violent methods more often, and this situation has remained stable throughout the 13-year period. Girls use non-violent methods to a greater extent, but young women aged 18-29 use violent and non-violent methods to almost the same extent. During the 13-year period studied, a change took place in the girls' and young women's choice of methods towards more violent methods in the 1980s compared with the 1970s. Regardless of sex, there are significantly (p less than 0.001) fewer married and more divorced people among those committing suicide compared with corresponding age groups in the overall population. PMID- 1496333 TI - Heritability of defects of far vision in young adults--a twin study. AB - A questionnaire to study defects in far vision in the Finnish Twin Cohort Study was sent to 600 twin pairs of 30 and 31 years of age divided equally by gender and zygosity. An excess in female prevalence of defects in far vision was observed (p less than 0.001). Validation of the questionnaire method to assess negative spherical equivalent of refraction was performed by asking the twins to send their last prescription for glasses. Accuracy of the questionnaire method to detect in far vision was tested using a subsample of cases where actual refraction obtained from the prescription for glasses was available. This actual refraction value was compared with the individuals answers to the questions of far vision. Of the subjects 5.5% were false negatives and 1.8% of the individuals were false positives. In 152 pairs one or both twins had a defect in far vision. Under a threshold liability model, the proportion of total (phenotypic) variance in liability attributable to additive genetic effects was 0.91 in this twin data, while no evidence for effects due to dominance was found. PMID- 1496334 TI - Diseases and symptoms as predictors of hospital care in an aged population. A prospective register-based study. AB - The association between diseases and symptoms and general hospital care was studied in a geographically defined population of 1040 persons aged 65 years or over (90% of the eligible non-institutionalized elderly). In eight years, 25% of the subjects used over 60 hospital bed-days. In age-controlled analyses high use of hospital care was predicted by chronic urinary infections and in women also by chronic bronchitis, diabetes mellitus and heart failure. Among men, the risk of high use of hospital care was greatest in those reporting chronic urinary infection (risk ratio 1.9), and among women in those reporting chronic bronchitis (2.1) and diabetes (2.0). As far as symptoms were concerned, the highest risks of hospital care were found in men reporting tremor (risk ratio 1.6) and depressive symptoms (1.5); and in women reporting memory disturbances and dizziness (risk ratios 1.9 and 1.7, respectively). High use of care was predicted by six symptoms in men and seven in women. Reported symptoms proved to be better predictors of high use of hospital care than reported diagnoses. PMID- 1496335 TI - Reliability of hospital discharge diagnoses of acute myocardial infarction. PMID- 1496336 TI - Alcohol consumption in a Danish cohort during 11 years. AB - A cohort living in Copenhagen County, originally consisting of 1198 persons, 577 men and 621 women, 40-years of age in 1976, was reexamined in 1981, and again in 1987. Of the original cohort 1052 (88%) participated in 1976, 992 (84%) in 1981, and 965 (85%) in 1987. The purpose of this study was to describe changes in alcohol consumption in the cohort, with the view of identifying subgroups, who have changed their alcohol consumption behaviour to a certain extent. Alcohol consumption was measured by the same questionnaire all three times as to the level of consumption and frequency. Alcohol consumption peaked in 1981 (45-year olds) with 10.4 drinks on average a week. Men increased their consumption by 8% and women by 37%. There was an overall downward tendency in the consumption frequency among men, whereas the opposite was the case among women. The two groups are converging toward a weekly consumption frequency. It seems now that women are leading the change toward a greater wine consumption in relative and absolute terms. It is therefore concluded that female consumption should be considered as a target in future preventive programmes. PMID- 1496337 TI - Intravenous drug abuse in young men: risk factors assessed in a longitudinal perspective. AB - The role of family background as well as behavioural and psychological factors as risk factors for intravenous drug abuse was analysed in a longitudinal study of 8168 Swedish men conscripted for military service in 1969-70. Information about risk factors was obtained from a survey of all Swedish conscripts. Records on intravenous drug abuse, during a followup ending in 1986, were obtained from a survey of intravenous drug abusers among persons brought to the Central police arrest in Stockholm. Strong predictors of intravenous drug abuse were contact with the police of juvenile authorities (RR = 22.3 95% CI 15.1-33.0), high alcohol consumption (RR = 9.2 95% CI 6.7-12.7) and psychiatric diagnosis at conscription (RR = 6.0 95% CI 4.5-8.1) and low social class (RR = 3.6 95% CI 2.2 5.9). In multivariate analyses, these factors and indicators of deviant behaviour still carried significantly increased relative risk for intravenous drug abuse, although several of them are interrelated. Low emotional control, nervousness, sleeping problems and other nervous problems were associated with an increased relative risk in univariate but not in multivariate analyses. PMID- 1496338 TI - [Various molecular mechanisms involved in the pathogenesis of type II diabetes and their potential therapeutic importance]. AB - The pancreatic beta cell presents functional abnormalities in the early stages of development of non-insulin dependent diabetes mellitus (NIDDM). The disappearance of the first phase of insulin secretion induced by a glucose load is a early marker of NIDDM. This abnormality could be secondary to the low expression of the pancreatic glucose transporter GLUT2. Together with the glucokinase enzyme, GLUT2 is responsible for proper beta cell sensing of the extracellular glucose levels. In NIDDM, the GLUT2 mRNA levels are low, a fact which suggests a transcriptional defect of the GLUT2 gene. The first phase of glucose-induced insulin secretion by the beta pancreatic cell can be partly restored by the administration of a peptide discovered by a molecular approach, the glucagon-like peptide 1 (GLP-1). The gene encoding for the glucagon is expressed in a cell-specific manner in the A cells of the pancreatic islet and the L cells of the intestinal tract. The maturation process of the propeptide encoded by the glucagon gene is different in the two cells: the glucagon is the main hormone produced by the A cells whereas the glucagon-like peptide 1 (GLP-1) is the major peptide synthesized by the L cells of the intestine. GLP-1 is an incretin hormone and is at present the most potent insulinotropic peptide. The first results of the administration of GLP-1 to normal volunteers and diabetic patients are promising and may be a new therapeutic approach to treating diabetic patients. PMID- 1496339 TI - [Role of thrombolysis in the treatment of cardiogenic shock following myocardial infarct]. AB - Of a total of 329 consecutive patients treated by thrombolysis with recombinant tissue-type plasminogen activator following myocardial infarction, 13 (4%) were in cardiogenic shock at the time of admission to hospital, and 4 others (1.2%) developed cardiogenic shock during their hospital stay. Overall hospital mortality for shock was high at 88% (15 of 17 patients), and shock was responsible for 57.6% (15 of 26) of all hospital deaths. Although several studies have shown that thrombolysis reduces the likelihood of cardiogenic shock developing after admission, our data confirm that it does not constitute effective treatment of established shock. More aggressive approaches, using thrombolysis together with angioplasty and mechanical ventricular assist devices, need to be evaluated. PMID- 1496340 TI - [Bone mineral density of the lumbar spine, the femoral neck and femoral diaphysis in a Genevan population sample]. AB - Bone mineral density (BMD) was measured by dual photon absorptiometry in the lumbar spine, femoral neck and midfemoral shaft in 209 women and 165 men aged 20 to 98 years recruited among the Geneva population. The prevalence of various factors (life style, calcium intake, body weight) which may be associated with a higher risk of osteoporosis was evaluated. Between the different skeletal sites, BMD was closely correlated. Nevertheless, BMD at one site failed to accurately predict BMD of another site. In each age class, BMD was dispersed over a wide range. Women and men had similar lumbar spine BMD. In women, BMD decreased after the fifth decade by 1.3, 1.0 and 2.6% year in the lumbar spine and femoral neck and shaft, respectively. Daily calcium intake from dairy products was 430 g and 750 g in women and men, respectively. Femoral shaft BMD was positively correlated with calcium intake. These BMD values obtained in a sample of the normal Geneva population should be of major help for the diagnosis of osteoporosis. PMID- 1496341 TI - [Severe herpes simplex encephalitis: course 15 years following decompressive craniotomy]. AB - Decompressive craniotomy with brain biopsy was carried out in two patients with herpes simplex virus encephalitis (HSE). In both cases the indication for surgery was based on the clinical picture of coma with rapidly progressive hemiparesis and on the computer tomographic finding of a large space-occupying lesion of in the temporal lobe accompanied by brain stem compression not controllable by medication. Both patients were treated with a standard dosage of vidarabine (Ara A 15 mg/kg/24 h) and corticosteroids after the operation. The improvement attained by surgery was very impressive in both cases. The massive neurological deficits (which also included subtotal aphasia in one case) regressed to a minimum in the following weeks. Both patients were followed up at yearly intervals for 15 years. They are now 36 and 76 years of age, both in a very satisfactory condition. Our observations show that decompressive craniotomy with duraplasty may be the crucial therapeutic measure in HSE with brainstem compression not controllable by medication. PMID- 1496342 TI - [Pathophysiology, prevention and therapy of altitude pulmonary edema]. AB - Alveolar hypoxia and resulting tissue hypoxia initiates the pathophysiological sequence of high altitude pulmonary edema (HAPE). Very rapid ascent to high altitude without prior acclimatization results in HAPE, even in subjects with excellent tolerance to high altitude. Upon acute altitude exposure, HAPE susceptible individuals react with increased secretion of norepinephrine, epinephrine, renin, angiotensin, aldosterone and atrial natriuretic peptide. In response to exercise at high altitude, subjects developing acute mountain sickness and HAPE secrete more aldosterone and antidiuretic hormone than subjects who remain well. This results in sodium and water retention, reduction of urine output, increase in body weight and development of peripheral edemas. The hypoxic pulmonary vascular response is enhanced in HAPE-susceptible subjects, thus favouring the development of severe pulmonary hypertension on exposure to high altitude. It has been postulated that uneven pulmonary vasoconstriction enhances filtration pressure in non-vasoconstricted lung areas, leading to interstitial and alveolar edema. The high protein content of the edema fluid in HAPE characterizes this edema as a permeability edema. The prophylactic administration of nifedipine prevents the exaggerated pulmonary hypertension of HAPE-susceptible subjects upon rapid ascent to 4559 m and thus prevents HAPE in most cases. This finding illustrates the crucial role of hypoxic pulmonary hypertension in the development of HAPE. The causal treatment of HAPE is descent, evacuation and administration of oxygen. Treatment of HAPE patients with nifedipine results in a reduction of pulmonary artery pressure, clinical improvement, increased oxygenation, decrease of the alveolar arterial oxygen gradient and progressive clearing of pulmonary edema on chest x-ray. Thus nifedipine offers a pharmacological tool for the treatment of HAPE. PMID- 1496343 TI - [Identification of alcoholism and therapeutic proposals: a study in a general hospital]. AB - Alcoholism is a frequent condition in patients admitted to general hospitals. The rate of identification of patients suspected to be alcoholic, the therapeutic measures proposed to such patients and their destination at hospital discharge were among the issues studied in the general wards of a department of internal medicine of an hospital in the French-speaking region of Switzerland. The Michigan Alcoholism Screening Test (MAST) was utilized systematically among all patients aged 20-75 years who where admitted consecutively to the department. Two cohorts matched for age and sex were thus formed: 102 alcoholics (MAST greater than or equal to 8) and 102 non-alcoholics (MAST less than or equal to 4). A diagnosis of alcoholism or of a syndrome of alcohol dependence was found in only 50% of all exit reports of the alcoholic cohort, whereas alcohol-related problems were identified on a verbal basis by the attending physician in 89% of cases. Therapeutic measures were proposed to 69% of female alcoholics and to 43% of male alcoholics, more frequently among patients with the highest MAST scores. In addition, at hospital discharge, alcoholic patients were more likely to be sent to a destination other than their place of residence than were the non-alcoholic patients. This study illustrates the low rate of identification and subsequent treatment of alcoholism among hospitalized patients. It also suggests that hospital stays should be used more frequently to increase the systematic identification of alcohol problems, increase awareness of alcoholism and provide information to both patients and those caring for them. PMID- 1496344 TI - [Bacillary angiomatosis: apropos of a case]. AB - We report a case of bacillary angiomatosis (BA), a recently described opportunistic infection, in a 30-year-old patient with Aids who was referred for a purplish vascular nodule on the forehead, of one-month duration, surrounded by similar smaller papules. For the previous 4 months he had suffered from progressive cachexia with fever, chills, night sweats, arthralgias and bone pain for which no infectious or malignant cause had been discovered after an extensive medical work-up. Histological examination of the skin lesions using Warthin Starry staining revealed lobular vascular proliferation and protuberant endothelial cells with clumps of small bacilli. These findings were confirmed by electron microscopy. We believe that this is the first case of BA diagnosed in Switzerland and discuss the skin lesions, systemic symptoms and evolution under antibiotic treatment. PMID- 1496345 TI - [Spondylitis due to Citrobacter diversus. Case report and review of Citrobacter diversus infections]. AB - Citrobacter diversus (C.d.) is an unusual human pathogen. Its pathogenic potency is small or nil, and in most cases it is isolated in combination with other organisms. Most isolates are of indeterminate clinical significance. Occasionally C.d. may cause opportunistic infections, especially in subjects with primary or secondary conditions of poor host defense, immunosuppressed patients or neonates. We report a case of C.d. vertebral osteomyelitis following C.d. pneumonia. The osteomyelitis was cured by surgery and chemotherapy. This case is interesting since it involves an otherwise healthy subject with no underlying disease. C.d. was isolated in blood during the episode of pneumonia and in bone four weeks later. No other case of Citrobacter diversus vertebral osteomyelitis has hitherto been described. PMID- 1496346 TI - [Neurogenic pain syndrome]. AB - Several pathophysiologic mechanisms are known which induce neuropathic pain in presence of peripheral nerve damage. They help to explain the clinical features of neuropathic pain syndromes and why causal and symptomatic treatments can be effective. However, careful analysis of every pain syndrome is necessary in order to select the type of pain management required. PMID- 1496347 TI - [Europe, what is that?]. PMID- 1496348 TI - [The status of the dentition in 2 Swiss population groups before the introduction of refined sugar]. AB - Caries and parodontitis have been one of the most spread diseases of mankind. In an archaeological study, 53 graves of Bernese patricians were exhumed. 22 skulls of adults with 392 teeth were examined. They lived between the 16th and the 18th century in the community of Worb BE. In some cases identification could be accomplished by comparison of oil paintings with skulls, using a computerized technique. The aim of this study was to evaluate the prevalence of caries, the loss of periodontal bone, the amount of calculus and of abrasion. To compare the dental situation with another population segment sex- and age-matched dates were used. This second population segment lived between the 12th and 18th century and belonged to a lower social class than the patricians from Worb. The comparison of these two groups showed significant differences only in the abrasion pattern. We conclude that the social class did not significantly influence most of the parameters studied here. The different abrasion pattern could be due to different dietary habits. PMID- 1496349 TI - [Experimental studies on the systemic toxicity of dental alloys free of precious metals]. AB - The systemic toxicity of five non-precious dental alloys was evaluated by help of an animal study. The pulverized dental alloys, filled in gelatine capsules, were orally administered to laboratory rats using a special esophageal application device. For each alloy examined randomized groups of ten experimental animals and ten control animals were used. For a period of seven days the experimental animals received daily 1000 mg alloy powder per kilogram body-weight. The animals of the control groups received daily empty gelatine capsules (placebo application). After two weeks all animals were killed and autopsies of the animals were performed. Histopathologic examinations of the lungs, kidneys, liver, small intestine and large intestine of all animals were done. With statistic significance (p less than 0.001) rats whom nickel-chromium alloys were administered orally showed serious pathologic reactions more frequently than placebo-treated control animals. Nickel-chromium alloys containing beryllium and/or gallium caused the strongest organic lesions. In contrary to this a dental cobalt-chromium alloy showed a very low systemic toxicity. The results of the study underline that preclinical toxicity testing of dental alloys is necessary in order to avoid systemic toxic lesions in man. PMID- 1496350 TI - [Oral fibromas and fibrosis. The clinical picture, histology and differential diagnosis]. PMID- 1496351 TI - [The representative of the Societe Suisse d'Odonto-Stomatologie for the questions of European integration]. PMID- 1496352 TI - ["We must resist far too strong encroachments of the state". Interview by Kurt Venner]. PMID- 1496353 TI - [Target group-specific prevention]. PMID- 1496354 TI - Free radicals and their scavenging in stroke. PMID- 1496355 TI - Home parenteral nutrition: an appraisal. PMID- 1496356 TI - Adult polycystic kidney disease: diagnosis presentation and genetic implications. PMID- 1496357 TI - Initial experience of an emergency helicopter transport service in the Outer Hebrides. AB - The outcome of patients transported by coastguard helicopter to the Lewis Hospital, Stornoway was studied for the first 30 months of the service. Although undoubtedly life-saving in some cases, some patients were transferred for trivial reasons. Feedback between the hospital and ships' captains and owners may reduce possible abuse of this service. Most patients were uplifted entirely appropriately. PMID- 1496358 TI - Surgical correction of congenital heart defects in adults. AB - From April 1987 to April 1991, 30 patients over the age of 15 years underwent surgery for congenital heart defects in the adult department of the Professorial Unit of Cardiothoracic Surgery, Royal Infirmary of Edinburgh. Eighteen were females (60%) and 12 were males (40%). Ages ranged from 15 to 68 years (mean 38.1). Six patients 20% had undergone previous cardiac surgery. Operative and hospital mortality was zero. Major postoperative complications occurred in three patients. In the follow-up period between three months and four years, there has been one late death. The spectrum of patients with congenital heart defects over the age of 15 was reviewed. The relatively late presentation of these defects and the indications for operating in adult life are discussed. PMID- 1496359 TI - Co-ordinating geriatric and general medical services; experience of a geriatric assessment ward in the Royal Infirmary of Edinburgh. AB - The paper describes the work of an assessment unit setup to provide a service for frail elderly patients admitted to general medical units at the Royal Infirmary of Edinburgh during the period of April 1989 to March 1990. Patients were selected on the basis of diagnosis, mental and physical function, age and social background and transferred to the assessment ward within 24 hours of admission to a medical ward. Most of the 376 patients admitted to the ward had a high level of multiple pathology and physical incapacity and a third had an acute confusional state. The mean length of stay was 19.4 days. There was a 13% mortality with 71% of survivors returning to their own homes. Review of mobility and self care capacity of the group revealed a striking increase in function during their stay in the ward. Factors increasing the likelihood of discharge included having a spouse, receiving support at home, having a low initial dependence rating. Adverse factors included having cerebrovascular disease, having dementia and initial maintenance of urine and faeces. PMID- 1496360 TI - Alcoholism, hyponatraemia and central neurological damage: more than pontine myelinolysis? AB - Three patients with alcoholism and severe hyponatraemia are described. Permanent neurological damage occurred in each case with cerebral, cerebellar or pontine damage from infarction or haemorrhage following correction of the biochemical disturbance. No patient developed Central Pontine Myelinolysis (CPM), the condition usually associated with profound hyponatraemia and its correction. PMID- 1496361 TI - A case of spontaneous hypothermia. AB - It is important to recognise any condition, however rare, which can be cured. We report a case of chronic hypothermia and its dramatic response to treatment. PMID- 1496362 TI - A matter of principle; the vital spirit. PMID- 1496363 TI - Conflict of interest policy. PMID- 1496364 TI - AIDS epicenter. PMID- 1496365 TI - Human SIV infections suspected. PMID- 1496366 TI - Bad news on second-hand smoke. PMID- 1496367 TI - Frustrated EMBL chief resigns. PMID- 1496368 TI - An NSF survey rattles some nerves. PMID- 1496369 TI - Forcing the evolution of an RNA enzyme in the test tube. PMID- 1496370 TI - Adhesion protein studies provide new clue to metastasis. PMID- 1496371 TI - Living dangerously after an AIDS test. PMID- 1496372 TI - Confusion on the cutting edge. PMID- 1496373 TI - When does intellectual passion become conflict of interest? PMID- 1496374 TI - NSF deals with conflicts every day. PMID- 1496375 TI - The logic of cell division in the life cycle of yeast. PMID- 1496376 TI - Directed evolution of an RNA enzyme. AB - An in vitro evolution procedure was used to obtain RNA enzymes with a particular catalytic function. A population of 10(13) variants of the Tetrahymena ribozyme, a group I ribozyme that catalyzes sequence-specific cleavage of RNA via a phosphoester transfer mechanism, was generated. This enzyme has a limited ability to cleave DNA under conditions of high temperature or high MgCl2 concentration, or both. A selection constraint was imposed on the population of ribozyme variants such that only those individuals that carried out DNA cleavage under physiologic conditions were amplified to produce "progeny" ribozymes. Mutations were introduced during amplification to maintain heterogeneity in the population. This process was repeated for ten successive generations, resulting in enhanced (100 times) DNA cleavage activity. PMID- 1496377 TI - The location of bound lipid in the lipovitellin complex. AB - The location of the bound lipid in the soluble lipoprotein lipovitellin has been determined by neutron crystallographic techniques. With the use of the contrast variation method, whereby the crystals are soaked in different H2O-D2O mixtures, the lipid has been found to occupy a large cavity in the protein whose structure had previously been determined by x-ray crystallography. The lipid appears to be bound in the form of a bilayer with the major protein-lipid interactions being hydrophobic and with the lipid headgroups projecting into the bulk solvent and into a solvent-filled space in the cavity. PMID- 1496378 TI - Vacuolar chitinases of tobacco: a new class of hydroxyproline-containing proteins. AB - The fungicidal type I chitinases contribute to the defense response of plants against pathogens. Two tobacco chitinases represent a different class of hydroxyproline-containing proteins. Hydroxyproline-rich proteins are predominantly extracellular, structural glycoproteins proteins that lack enzymatic activity and contain many hydroxyproline residues. In contrast, type I chitinases are vacuolar enzymes. They are not glycosylated and contain a small number of hydroxyproline residues restricted to a single, short peptide sequence. PMID- 1496379 TI - Neuronal domains in developing neocortex. AB - The mammalian neocortex consists of a mosaic of columnar units whose development is poorly understood. Optical recordings of brain slices labeled with the fluorescent calcium indicator fura-2 revealed that the neonatal rat cortex was partitioned into distinct domains of spontaneously coactive neurons. In tangential slices, these domains were 50 to 120 micrometers in diameter; in coronal slices they spanned several cortical layers and resembled columns found in the adult cortex. In developing somatosensory cortex, domains were smaller than, and distinct from, the barrels, which represent sensory input from a single vibrissa. The neurons within each domain were coupled by gap junctions. Thus, nonsynaptic communication during cortical development defines discrete multicellular patterns that could presage adult functional architecture. PMID- 1496380 TI - Mechanistic aspects of signaling through Ras in NIH 3T3 cells. AB - Serum and growth factors can increase the proportion of Ras in the active guanosine triphosphate (GTP)-bound form. Growth factors might stimulate guanine nucleotide exchange or decrease the activity of the guanosine triphosphatase activating proteins GAP and neurofibromin (NF1). In NIH 3T3 cells that overexpress the mutant Ras protein His116, which releases bound guanine nucleotide at a constitutively high rate and retains sensitivity to GAP and NF1, the proportion of GTP bound to the His116 protein was not altered by serum or platelet-derived growth factor. However, these mitogens increased the proportion of Ras in the GTP-bound form in cells that overexpressed control Ras proteins with a normal intrinsic rate of guanine nucleotide release. The amount of GTP bound His116 or control Ras proteins was higher in cells at low density than in cells at high density, which have more GAP-like activity. The lower proportion of GTP-bound Ras in NIH 3T3 cells at high density may result from increased GAP-like activity. By contrast, serum and platelet-derived growth factors appear to stimulate guanine nucleotide exchange. PMID- 1496381 TI - Specialized role for a murine class I-b MHC molecule in prokaryotic host defenses. AB - Although nonclassical (class I-b) gene products represent the majority of murine major histocompatibility complex (MHC) genes, the role of these relatively nonpolymorphic molecules remains uncertain. Recently, one such protein, H-2M3 (formerly designated Hmt), was shown to bind and specifically present N formylated peptides to cytotoxic T lymphocytes. Because N-formylation is characteristic of prokaryotic proteins, this MHC molecule may be especially adapted for a role in the mammalian defense against bacterial attack. The current studies demonstrate that an MHC molecule, indistinguishable from H-2M3, presents antigens derived from the intracellular pathogen Listeria monocytogenes to Listeria-specific CD8+ cells. PMID- 1496382 TI - A protein kinase substrate identified by the two-hybrid system. AB - A genetic method, the two-hybrid system, was used to identify four genes encoding proteins that interact with the SNF1 protein kinase from yeast. One of the genes, SIP1, was independently isolated as a multicopy suppressor of defects caused by reduced SNF1 kinase activity, and genetic evidence supports its function in the SNF1 pathway. The SIP1 protein co-immunoprecipitated with SNF1 and was phosphorylated in vitro. Thus, the two-hybrid system, which is applicable to any cloned gene, can be used to detect physical interactions between protein kinases and functionally related substrate proteins. PMID- 1496384 TI - Coppola looking for an AIDS "cure". PMID- 1496383 TI - Participation in normal immune responses of a metastasis-inducing splice variant of CD44. AB - A variant of the glycoprotein CD44 (CD44v) that shares sequences with variants causally involved in metastasis formation is transiently expressed on B and T lymphocytes and macrophages after antigenic stimulation and in the postnatal period. Antibodies to the variant hinder in vivo activation of both B and T cells. The observation that a protein domain that is expressed on CD44 and required for the lymphatic spread of tumor cells can catalyze an essential step in the process of lymphocyte activation supports the idea that metastasizing tumor cells mimic lymphocyte behavior. PMID- 1496385 TI - Science in court: a culture clash. PMID- 1496387 TI - Superconducting Super Collider. Senate issues a stay of execution. PMID- 1496386 TI - Gain for space station; pain for NSF. PMID- 1496388 TI - Myoblast therapy. PMID- 1496389 TI - Researchers call for time out on cell-transplant research. PMID- 1496390 TI - NIH to size up growth hormone trials. PMID- 1496391 TI - NIH wrestles with furor over conference. PMID- 1496393 TI - HHS starts audit of grant fund use. PMID- 1496392 TI - Contracting practices at EPA labs go under the microscope. PMID- 1496394 TI - Uganda to host AIDS vaccine therapy trials. PMID- 1496395 TI - DNA shows unexplained patterns writ large. PMID- 1496396 TI - Stagnation in the decline of the world population growth rate during the 1980s. AB - The world human population growth rate after World War II passed through three phases: the rise in the 1950s and 1960s, the fall (though still at a positive level) in the 1970s, and the plateau in the 1980s. The rise was produced by the global decline in death rates, the fall was mainly due to the reduction of fertility in a number of developing countries, and the stagnation of growth rate decline was attributable to three major factors. First, substantial fertility declines started around 1970 and stalled around 1980 in both China and India. Second, the age structure of population changed in favor of higher birth rates. Third, although fertility started to decline significantly around 1970 mainly in East Asia, Southeast Asia, and Latin America, few countries have begun fertility declines since then. Many countries in sub-Saharan Africa and South Asia have not started substantial fertility reductions, deepening the gap between developing countries that are moving to lower fertility levels and those that are left behind. PMID- 1496397 TI - Uranium bioaccumulation by a Citrobacter sp. as a result of enzymically mediated growth of polycrystalline HUO2PO4. AB - A Citrobacter sp. accumulates heavy deposits of metal phosphate, derived from an enzymically liberated phosphate ligand. The cells are not subject to saturation constraints and can accumulate several times their own weight of precipitated metal. This high capacity is attributable to biomineralization; uranyl phosphate accumulates as polycrystalline HUO2PO4 at the cell surface. The precipitated metal is indistinguishable from crystalline HUO2PO4.4H2O grown by chemical methods. PMID- 1496398 TI - Evidence from 18S ribosomal RNA sequences that lampreys and hagfishes form a natural group. AB - Lampreys and hagfishes (cyclostomes) traditionally were considered to be a natural (monophyletic) group. Recently, the consensus of opinion, based largely on morphological analyses, has shifted to a view that lampreys are more closely related to jawed vertebrates (gnathostomes) than to hagfishes. Phylogenetic comparisons of 18S ribosomal RNA sequences from two hagfishes, two lampreys, a tunicate, a lancelet, and a number of gnathostomes support the monophyly of the cyclostomes. These data force a reassessment of several features of early vertebrate evolution. PMID- 1496399 TI - Immunosuppression in vivo by a soluble form of the CTLA-4 T cell activation molecule. AB - In vitro, when the B7 molecule on the surface of antigen-presenting cells binds to the T cell surface molecules CD28 and CTLA-4, a costimulatory signal for T cell activation is generated. CTLA4Ig is a soluble form of the extracellular domain of CTLA-4 and binds B7 with high avidity. CTLA4Ig treatment in vivo suppressed T cell-dependent antibody responses to sheep erythrocytes or keyhole limpet hemocyanin. Large doses of CTLA4Ig suppressed responses to a second immunization. Thus, costimulation by B7 is important for humoral immune responses in vivo, and interference with costimulation may be useful for treatment of antibody-mediated autoimmune disease. PMID- 1496400 TI - Hypovirulence of chestnut blight fungus conferred by an infectious viral cDNA. AB - Strains of the chestnut blight fungus Cryphonectria parasitica that contain viral double-stranded RNAs often exhibit reduced virulence. Such hypovirulent strains act as biocontrol agents by virtue of their ability to convert virulent strains to hypovirulence after anastomosis. Transformation of virulent C. parasitica strains with a full-length complementary DNA copy of a hypovirulence-associated viral RNA conferred the complete hypovirulence phenotype. Cytoplasmic double stranded RNA was resurrected from the chromosomally integrated complementary DNA copy and was able to convert compatible virulent strains to hypovirulence. These results establish viral double-stranded RNA as the casual agent of hypovirulence and demonstrate the feasibility of engineering hypovirulent fungal strains. PMID- 1496403 TI - Case of the season. Solitary neurofibroma with comminuted pathological fracture of C6. PMID- 1496401 TI - Interferon-dependent tyrosine phosphorylation of a latent cytoplasmic transcription factor. AB - The interferon-alpha (IFN-alpha)-stimulated gene factor 3 (ISGF3), a transcriptional activator, contains three proteins, termed ISGF3 alpha proteins, that reside in the cell cytoplasm until they are activated in response to IFN alpha. Treatment of cells with IFN-alpha caused these three proteins to be phosphorylated on tyrosine and to translocate to the cell nucleus where they stimulate transcription through binding to IFN-alpha-stimulated response elements in DNA. IFN-gamma, which activates transcription through a different receptor and different DNA binding sites, also caused tyrosine phosphorylation of one of these proteins. The ISGF3 alpha proteins may be substrates for one or more kinases activated by ligand binding to the cell surface and may link occupation of a specific polypeptide receptor with activation of transcription of a set of specific genes. PMID- 1496402 TI - Activation of transcription factors by interferon-alpha in a cell-free system. AB - The signal transduction mechanisms of interferons (IFNs) remain unclear partly because no effect of IFN has been reproducible in a cell-free system. IFN-alpha rapidly induces the transcription of a set of early response genes, and a multicomponent transcriptional activator, interferon stimulated gene factor 3 (ISGF3), is activated within minutes after binding of IFN-alpha to its receptor. A system was developed in which IFN-alpha activated ISGF3 in homogenates of HeLa cells. Subcellular fractionation revealed that incubation of a plasma membrane enriched fraction with IFN-alpha was sufficient to activate the regulatory subcomponent of ISGF3. PMID- 1496404 TI - Abdominal computed tomography in blunt trauma. PMID- 1496405 TI - Imaging in acute thoracic trauma. PMID- 1496406 TI - Diagnostic and therapeutic angiography in the trauma patient. PMID- 1496407 TI - [The words of the Pope on the ethics of treating pain in terminal patients]. PMID- 1496408 TI - [The ethics of the doctor-patient relationships]. PMID- 1496409 TI - [Aged persons: the present and future]. PMID- 1496410 TI - Structured ambiguity and the definition of psychiatric illness: adjustment disorder among medical inpatients. AB - Adjustment disorder is one of the most common psychiatric diagnoses given to patients hospitalized for medical and surgical problems. This article argues that the diagnosis, in this context, often serves strategic, non-clinical ends for consultation-liaison psychiatrists, who must negotiate their interstitial position through an essentially ambiguous diagnosis. In these cases, 'adjustment disorder' emerges from and reproduces tensions between such cultural dichotomies as mind/body and social/individual that marginalize psychiatry in medical settings. PMID- 1496411 TI - Toward a cultural history of the personality disorders. AB - Psychiatric categories in general, and the personality disorders in particular, remain problematic and contested. This is no where more clearly evident than in the case of the 'antisocial' and 'histrionic' personality disorders. In part, the problem is related to the observation of differences in gender distribution. Men are more likely to be diagnosed 'antisocial' than women, and women are more likely to be diagnosed 'histrionic' than men. Confusion results partly from the suspicion that these categories may be culturally conditioned and therefore spurious as medical labels true in some 'absolute' sense. This paper argues that the antisocial and histrionic disorders have cultural histories, representing (in extreme form) values strongly congruent with familiar cultural stereotypes: the 'independent' male and the 'dependent' female. The process by which these values were delegated to men and women is examined, and then shown to be at least partly determinative of later developments in the formation of psychiatric categories. PMID- 1496412 TI - The social construction of premenstrual syndrome. AB - In 1931 a physician coined the term Premenstrual Tension, thereby commencing an extensive biomedical inquiry into the relationship between women's menstrual cycle and the occurrence of physical, emotional and behavioral changes. However, despite 58 years of scientific research, fundamental questions remain unanswered. For example, there is still no consensus on the definition of PMS. This, in turn, has led to disagreement among researchers about which medical specialty is best suited for diagnosing and treating PMS. Is PMS a disease whose pathology is best understood by physicians in reproductive medicine or in psychiatry? This paper argues that the inconclusiveness surrounding PMS is symptomatic of the persistence of cultural beliefs in the production (and reproduction) of medical knowledge. The roots of these cultural beliefs and their 'naturalness' in the context of Western ideas about reason, rationality and women are explored in the first section. The second section discusses the ubiquity of these same cultural beliefs in contemporary scientific research of PMS and in the controversy surrounding the proposed psychiatric diagnostic category of Late Luteal Phase Dysphoric Disorder (LLPDD). Finally, a new, anthropologically and sociologically informed approach to understanding the phenomenon of PMS is suggested. PMID- 1496413 TI - Psychiatry as social ordering: anorexia nervosa, a paradigm. AB - From a psychiatric perspective, anorexia nervosa (hereafter referred to as 'anorexia') is an enigmatic illness. This paper attempts to explain why this is so, describing anorexia as a western cultural phenomenon whose psychiatric explanations and treatments actually participate in the sociocultural processes that inform this syndrome. Anorexia reveals a form of contemporary control over the female body, and psychiatry, as a western discipline, institutionalizes a mind-over-body (objective) ideology that is part of this project. Various psychiatric theories of anorectic etiology and their corresponding methods of treatment are analyzed in this light, and a general framework for understanding the discipline of psychiatry as a mode of social control is offered. PMID- 1496414 TI - Adolescence as a culture-bound syndrome. AB - In keeping with an expanded definition of culture-bound syndromes, this paper argues that adolescence in American society has been 'medicalized' into a full blown symptom complex or pathologic condition. Culture-bound syndromes in highly differentiated societies such as the U.S., may be taxonomically sorted by distinctive cultural identity system domains of age, gender, family, vocation and ethnicity. PMID- 1496415 TI - DSM-III-R and religion. AB - The interpretation of religion in DSM-III-R contains considerable negative bias and contributes to unfair stereotypes of religious persons. Particularly new religious movements and religious conversion are unfairly interpreted under the DSM-III-R heading, 'Dissociative Disorder Not Otherwise Specified'. It is suggested that a more balanced and respectful interpretation of religion is needed in DSM-III-R, since psychiatry through its official nomenclature should not contribute to social intolerance of religious nonconformity. PMID- 1496416 TI - The role of culture in a theory of psychiatric illness. AB - A medical theory of phenomena thought of as psychiatric would rely on concepts and seek explanations that pertain to the concerns of biomedicine. A social theory of the psychiatric needs concepts and seeks explanations that pertain to concerns of the social and cultural sciences. Some of the requirements of such a social theory are reviewed with an emphasis on why and how the concept of culture is important. The Western medical bias of psychiatric illness needs to be faced as well as the problem of cultural relativism. The paper discusses the heuristic usefulness of a concept of human behavioral breakdowns. The many ways in which culture influences knowledge and practice of biomedical psychiatry are examined critically. The scope of a social theory of the psychiatric is also outlined. PMID- 1496417 TI - Isolation and characterization of radiation-reduced hybrids containing portions of the proximal long arm of the human X chromosome: identification of hybrids containing the Menkes' disease locus. AB - The proximal long arm of the human X chromosome (Xcen----Xq13) encompasses an estimated 23 megabases of DNA and contains numerous identified genetic loci. In order to generate a highly enriched source of DNA from this region, radiation reduced human-hamster hybrids were constructed and screened to identify those that contained at least part of proximal Xq. Eight such hybrids were identified and characterized by Southern blot and fluorescence in situ hybridization analyses to determine more precisely the human DNA complement in each. One hybrid contains the entire proximal long arm and will be useful for mapping Xcen----Xq13 in its entirety and for localizing genes within this region. Another hybrid contains a smaller portion of the proximal long arm that includes the region reported to contain the gene for Menkes' disease. PMID- 1496419 TI - Human chromosome 19 contains the neurotrophin-5 gene locus and three related genes that may encode novel acidic neurotrophins. AB - Differentiation, survival, and function of the vertebrate neurons are controlled by multiple, target-derived neurotrophic factors. The best characterized mammalian neurotrophic factors are four structurally related 13 to 14 kDa basic proteins, collectively known as neurotrophins. Here we describe the identification of a gene cluster localized on human chromosome 19 that contains neurotrophin-5 (NT-5) and that may encode three additional acidic members of this protein family. The three novel partial open reading frames (ORFs), designated neurotrophin-6-alpha (NT6-alpha), NT6-beta and NT6-gamma, are 95% identical to each other and 75% identical to NT5. The putative mature N-terminal portion of NT6 ORFs does not contain a typical dibasic cleavage site and lacks two out of six cysteines that are conserved among the neutrophins. The unique structures of NT6-alpha, -beta, and -gamma suggest that if the NT6 open reading frames indeed code for functional proteins, these proteins may display novel functions and may act through a distinct class of receptors. In the human, both NTF5 and NTF6 gene loci were mapped to chromosome 19 by Southern analysis of somatic cell hybrid panels. In mouse, the NT5 gene (Ntf-5) was assigned to chromosome 7 and no sequences representing NT6 homologs were identified. PMID- 1496418 TI - At least two distinct epigenetic mechanisms are correlated with high-frequency "switching" for APRT phenotypic expression in mouse embryonal carcinoma stem cells. AB - A series of clones displaying high frequency "switching" phenotypes for expression of the adenine phosphoribosyltransferase (aprt) gene were previously isolated from the P19 mouse embryonal carcinoma stem cell line. Most clones contained only one aprt allele. We report here the characterization of each of these clones with regards to enzymatic activity, mRNA steady state levels, DNA methylation, and chromatin conformation. When clones were selected for resistance to the purine analog 2,6-diaminopurine, which requires markedly reduced levels of APRT enzymatic activity, two distinct classes were observed. The first class was associated with reduced or undetectable levels of aprt mRNA, hypermethylation of the 5' CpG island, and a closed chromatin conformation within this region. When clones of this class were selected for reacquisition of APRT enzymatic activity they were found to have increased mRNA levels, a hypomethylated CpG island, and an open chromatin conformation. In contrast, the second class of clones displayed wild-type levels of mRNA, CpG island hypomethylation, and an open chromatin conformation regardless of whether they were selected for the presence or absence of APRT enzymatic activity. The implications of these results for general mechanisms of epigenetic change in somatic cells and the possibility that expression of the mouse aprt gene may be developmentally regulated are discussed. PMID- 1496420 TI - Circulating human or canine factor IX from retrovirally transduced primary myoblasts and established myoblast cell lines grafted into murine skeletal muscle. AB - We have used retroviral vectors to introduce human or canine factor IX cDNAs into cultured primary murine and canine myoblasts and into the established murine myoblast cell line C2C12. In all cases, the stably infected cells produced biologically active factor IX in culture and secreted detectable amounts into the culture medium both before and after differentiation of the cells into myotubes. Myoblasts and differentiated myotubes are therefore capable of performing all the posttranslational modifications of the coagulation factor required for biological activity. We have grafted the genetically modified myoblasts into skeletal muscles of nude mice and have detected stable levels of circulating human factor IX for up to two months after grafting. We propose that grafting genetically modified primary myoblasts or established myoblast cell lines into skeletal muscle may represent a useful approach to gene therapy for a variety of genetic diseases, including intrinsic muscle disease and defects in circulating proteins as in the hemophilias. PMID- 1496421 TI - Directed isolation of human genes that escape X inactivation. AB - Existing methodologies have been combined to produce a directed approach to the isolation of human genes that escape X inactivation. A mouse-human somatic cell hybrid line was established that has an inactive X as its only human chromosome, and nuclear RNA from this cell line was used to construct a cDNA library. Transcribed human sequences were isolated by screening the library with labeled human DNA. The corresponding genomic sequences were isolated in phage or cosmid clones, and exons were identified by detection of transcripts on northern blots. By these means three human loci have been identified that contain genes expressed from an inactive X chromosome. Fluorescence in situ hybridization has been used to map these genes to Xp21.1-22.1, Xp22.1-22.2, and terminal Xp/Yp. One of the three genes (XE45) corresponds to the ZFX gene, while the other two genes (XE7 and XE59) represent novel cloned sequences. Physical and genetic evidence indicate that XE7 is a newly identified pseudoautosomal gene. PMID- 1496422 TI - Generation and characterization of a human chromosome 9 cosmid library. AB - A cosmid library has been constructed from the hamster-human hybrid cell line PK 87-9, which contains chromosome 9 as its sole known human component. Ten thousand colonies were produced, of which approximately 200, or 2%, contain human material. Fifty of these 200 were regionally mapped by an Alu-primed PCR product hybridization procedure. These cosmids were localized to all regions of chromosome 9, but were especially concentrated in the distal portion of 9q. The map location derived by the Alu-primed PCR product hybridization procedure was compared to the map location derived by fluorescent in situ hybridization. Assignment of chromosomal location by the two methods was correspondent in all but a few cases. The presumptive presence of HTF islands was investigated for 130 cosmids by digestion with the restriction enzyme NotI. Twenty percent of cosmids contained at least one NotI site. A number of simple sequence repeat polymorphisms identified from the cosmid set were characterized and will provide a link between the genetic and physical maps for this chromosome. PMID- 1496424 TI - Unusual occupational diseases. PMID- 1496423 TI - Construction and characterization of radiation hybrids for chromosome 9, and their use in mapping cosmid probes on the chromosome. AB - Radiation hybrids were produced from a monochromosomal microcell hybrid (PK87-9) which contains only human chromosome 9 with an inserted marker on 9p. Doses of radiation ranging from 1000 to 8000 rads were used to produce a series of hybrids with different size fragments of human chromosome 9. The inserted dominant selectable marker was used to select for hybrids that preferentially maintain fragments of 9p. A panel of 53 radiation hybrids were characterized for 17 chromosome 9 markers. In addition, 17 hybrids were analyzed by fluorescent in situ hybridization (FISH). Hybrids were produced with breaks on both 9p and 9q, many of which appear to contain a single fragment of human chromosome 9. These hybrid cell lines were used to regionally localize 31 cosmids isolated from a chromosome 9 cosmid library. Six cosmids were mapped to intervals on 9p, six cosmids mapped to the centromeric region of the chromosome, and 19 mapped to 9q. PMID- 1496425 TI - Diseases of unusual occupations: an historical perspective. AB - A compilation of conditions deemed unusual from previous eras serves to highlight now obsolete jobs and remind that even relatively prevalent occupational disorders of today will be viewed retrospectively as strange in the proximate future. Discussed are coal miners' nystagmus, scrotal cancer in chimney sweeps, phossy jaw, hatters' shakes, painters' colic, potters' rot, chauffeurs' knee, glanders, caisson disease, and others. PMID- 1496426 TI - Unusual occupationally related disorders of the lung: case reports and a literature review. AB - Diseases of the lung are among the work-related conditions most widely recognized among nonspecialists and the lay public. Five pulmonary conditions for which occupational or environmental exposures are not typically emphasized are reviewed here in their clinical-pathologic context. These are diffuse alveolar hemorrhage, lipoid pneumonitis, granulomatous lung disease, pulmonary alveolar proteinosis, and pulmonary vascular disease. PMID- 1496427 TI - Unusual occupational rheumatologic and musculoskeletal disorders. AB - Musculoskeletal disorders are among the most common clinical occupational problems, but occupational rheumatologic diseases are among the rarest. The identification of one or more cases of unusual diseases or epidemiologically unusual presentations must alert the clinician to the possibility of group exposure and risk and emphasizes the need to explore these using the model of "sentinel health event." Cumulative trauma disorders, including thoracic outlet syndrome and reflex sympathetic dystrophy syndrome, and occupational rheumatologic disorders of other etiology (Raynaud's phenomenon, scleroderma, fluorosis, osteomalacia, aseptic necrosis, and Caplan's syndrome) are reviewed. PMID- 1496428 TI - Unusual occupational gastrointestinal and hepatic disorders. AB - Acute centrolobular necrosis, cancers related to occupational chemical exposures, and infectious hepatitis are widely recognized, but other occupational and environmental diseases of the gastrointestinal tract are underemphasized by comparison. This review explores the associations between workplace exposures and steatosis, increased liver microsomal activity, cholestatic liver injury, portal fibrosis and hepatic sclerosis, granulomatous liver disease, porphyria cutanea tarda, peptic ulcer disease, pancreatitis, gastroenteritis, celiac disease, and pneumatosis cystoides intestinalis. PMID- 1496429 TI - Renal diseases of occupational origin. AB - Environmental toxicants, including those from industrial sources, represent potentially preventable causes of chronic kidney disease. The etiology of chronic renal failure of recognized occupational origin (other than malignancies) is reviewed, including that for heavy metals, organic solvents, beryllium, and silicon. PMID- 1496430 TI - Cardiotoxicity in the workplace. AB - A number of chemicals have been implicated in the causation of cardiovascular disease, although often in individual patients causality for any specific toxic exposure is difficult to establish. This review discusses toxic cardiovascular disease from specific toxins from the perspective of the types of injury and details epidemiology, mechanisms of toxicity, and clinical features. Discussed are carbon disulfide, carbon monoxide, organic nitrates, halogenated hydrocarbons, lead, cobalt, arsenic/arsine, and cadmium and antimony. PMID- 1496432 TI - Occupational and environmental causes of parkinsonism. AB - Occupational causes of parkinsonism have usually been identified by direct temporal association of an exposure with disease symptoms, although recently a latent period between exposure and disease causation is being investigated. This review presents the definition of parkinsonism as contrasted with Parkinson's disease, notes the general concepts important to the consideration of toxic effects on the central nervous system, and addresses each group of agents known to cause parkinsonism, including common sources of exposure, clinical course, and proposed mechanisms of toxicity. Agents discussed include manganese, carbon disulfide, organic solvents, carbon monoxide, and MTPT and similar agents. PMID- 1496431 TI - Endocrine disorders of occupational and environmental origin. AB - Many compounds used and produced in industry are potentially toxic to the endocrine system. The importance of medical surveillance in the workplace is emphasized in light of the increasing numbers of women in industry and the associated potential reproductive risks. Endocrine-toxic compounds also can gain wider access to entire communities through designed release to the environment (as with pesticides), accident, or disposal of toxic waste. The mechanisms of various industrial toxins in causing disease of the thyroid, testes and ovary, and pancreas are reviewed. PMID- 1496433 TI - Occupational and environmental disorders of the special senses. AB - Occupational hazards to vision, hearing, balance, olfaction, and taste typically constitute a small fraction of specialty medical practices in ophthalmology and otolaryngology. With the possible exception of noise-related hearing loss and VDT eye hazards, the scientific literature regarding these hazards tends to be scattered and variably accessible to occupational medicine practitioners. It is hoped that the current review will heighten the appreciation of these hazards among both generalists and specialists, and will encourage future documentation and reporting of this interesting group of disorders. PMID- 1496434 TI - Occupational health effects of nonionizing radiation. AB - Nonionizing radiation includes electromagnetic energy distributed as near ultraviolet and visible light, infrared radiation, microwaves, radio frequencies, and very low frequency and extremely low frequency alternating electric and magnetic fields, and almost every member of modern society is exposed to it in some form. Usually the intensity of exposure is low in the general population but can be greatly increased in the workplace. The forms of nonionizing radiation are described and their physical characteristics, occupational sources, biologic effects, and exposure criteria are delineated. PMID- 1496435 TI - Unusual occupational toxins. AB - Occupational and environmental medicine affords encounters with many unusual toxins, ranging from exotic metals to rocket fuels. Twelve of the most unusual industrial toxins are reviewed here and their clinical manifestations and treatments explored: acetonitrile, acrylonitrile, boron hydrides, dimethylaminopropionitrile, dimethylformamide, hydrazines, methyl isocyanate, 2 nitropropane, phosphine, Stalinon, tellurium, and vanadium. PMID- 1496436 TI - Surgical recanalization of occluded peripheral arteries. AB - This article, reflecting on the surgical recanalization of occluded peripheral arteries, has exposed the very essence of vascular surgery. Only the pioneering cardiac anomalies repaired by Gross (patent duct arteriosus, 1938), Blalock and Taussig (tetralogy of Fallot, 1944), and Crafoord and Nylin (coarctation, 1945) and the legendary aortic grafting operations of Oudot (occlusion, 1950) and Dubost and coworkers (aneurysm, 1951) are not a part of this article. The contributions to surgical recanalization of the occluded peripheral arteries are numerous. Some are well conceived, and others are innovative. Perhaps the most significant technique of all, endarterectomy itself, began purely as a serendipitous event. The startling impact of dos Santos' revolutionaly "disobliteration" was realized at once. Intimal injury during the operation did not cause inevitable thrombosis, as historically taught. Thus, all vascular interventions, either endarterectomy, graft repair, or the newer endovascular techniques discussed in this issue, would not have been developed without the understanding of the tolerance of the human intima to injury. Thromboendarterectomy, the basis of surgical recanalization of occluded arteries, unlocked the mystery of arterial rethrombosis after intervention. Recognizing these crucial facts, it will have a lasting place in the expanded discipline of vascular disease and its treatment. Dos Santos, the European founder of endarterectomy, and Wylie, the American pioneer and proponent of endarterectomy, were great friends in life (Fig. 4) and would certainly be pleased to see the further development of technology aimed at the treatment of atherosclerotic obstruction of the peripheral arteries. PMID- 1496437 TI - Political issues in endovascular surgery. AB - "Political issues" may determine the relative progress if not the ultimate success and acceptance of endovascular surgery as much as its intrinsic merits. These issues include turf battles, commercialization of newly developing technologies, unethical advertising, and self-serving reporting practices in presenting clinical results. Acceptable indications, methods of evaluating results, standardized reporting practices, appropriate "gold standards" for comparison, and controlled trials (without premature release) are recommended, as well as an emphasis on the future need for proper training and credentialing and quality assurance programs. PMID- 1496438 TI - Angiography of the lower extremity in atherosclerotic vascular disease. Current techniques. AB - With the vast array of technology available, detailed diagnostic information is now routinely obtained in patients with peripheral vascular disorders. In addition, percutaneous intervention and advanced surgical techniques now safely permit the patient to return to an active life, and in advanced vascular disease, the extremity can be salvaged when previously the only option was amputation. We feel strongly that the maximum amount of information about the arterial system should be obtained throughout the patient's management. In addition, these complex procedures require considerable experience and judgment, and our practice of ongoing communication with the vascular surgery staff during both the diagnostic and the therapeutic phases of the patient's treatment has been extremely beneficial. PMID- 1496439 TI - Angioscopy. AB - Endoscopy of the vascular system has evolved over recent years from an experimental procedure to a sophisticated diagnostic and therapeutic technique for surgical or percutaneous interventions of the peripheral vascular system. Particularly in procedures involving remote instrumentation of arteries, the angioscope provides a method of controlled guidance and a monitor of the effects of the various instruments on the vessel wall and allows immediate assessment of results. Angioscopic examination reveals the extent of intimal injury after angioplasty, in situ vein preparation, trauma, and thrombectomy and gives insights into the mechanisms and effects of endovascular devices. PMID- 1496440 TI - Intravascular ultrasonography. AB - Intravascular ultrasonography is developing rapidly as a method for defining the transmural anatomy of vascular structures, with diagnostic and therapeutic applications. The ultrasound technology not only has unique diagnostic capabilities by defining the distribution and character of lesions, but also provides accurate control information regarding efficacy of angioplasty methods. An exciting recent development is the three-dimensional reconstruction of two dimensional images which permits global examination of luminal and transmural vessel morphology. This technology may enable improved guidance of intraluminal devices to enhance lesion removal without damaging adjacent normal wall structure and appropriate device selection by differentiating specific plaque characteristics. PMID- 1496441 TI - Laser angioplasty. AB - Laser energy has the potential for selective ablation of atherosclerotic plaque through minimally invasive means. As currently practiced, laser angioplasty requires the adjunct of balloon angioplasty in most cases and has limited application compared with more conventional methods of revascularization. However, new advances in guidance systems, delivery devices, and laser sources may allow realization of the full benefit of this technology at some point in the future. PMID- 1496442 TI - Status of peripheral atherectomy. AB - So far, all atherectomy devices have failed to reduce the restenosis rate of standard balloon angioplasty. Despite actual removal, debulking, and even polishing of the atherosclerotic intima, the arterial wall trauma invariably incites intimal hyperplasia. Until the problem of restenosis can be solved, atherectomy will be limited to those instances when balloon angioplasty is ineffective or contraindicated. Each device has its own peculiarities. We prefer to use the Simpson catheter for eccentric lesions in the iliofemoral or femoropopliteal regions, the Auth Rotablator for short lesions in the infrageniculate vessels, and the TEC for longer lesions in the femoropopliteal regions. Adjunctive balloon angioplasty may or may not be required. Ahn and Moore have illustrated specific clinical strategies for peripheral atherectomy. PMID- 1496443 TI - Thrombolytic therapy. AB - Thrombolytic therapy may be used as either sole treatment or an adjunct to surgery in both arterial and venous disease. The age of the clot, particularly with venous thrombosis, determines the probability of successful lysis, with recent clot being highly susceptible to lytic therapy. The technique of thrombolysis is also an important determinant of the outcome, with high doses delivered directly into the clot over short time periods associated with the highest success and the lowest complication rates. Because systemic therapy increases the risk of bleeding from a remote site, techniques to concentrate the lytic agent within the clot, such as intraoperative high-dose and isolated-limb therapy, may achieve a higher success with a lower complication rate. Newer agents, which are clot specific, will be available for lytic therapy and should result in even higher success rates while minimizing systemic complications. PMID- 1496444 TI - Intravascular stents. Status of development and clinical application. AB - A variety of intravascular stents are currently under investigation and in various stages of achieving governmental approval for clinical application. The Palmaz balloon-expandable stent has recently been approved for use in the iliac arteries based on specific indications for application. Stents are generally described according to their method of deployment and are either balloon expandable or self-expanding. Clinical application has been proved in the iliac arteries, where the use of stents has greatly enhanced the treatment of patients with total occlusions, complex dissections, and restenoses. Additionally, there is promise that stents will enhance the percutaneous treatment of renal artery ostial lesions, infrainguinal arterial lesions, and strictures in large veins. Clearly, the increasing application of intravascular stents has ushered in a new era of percutaneous intervention. PMID- 1496445 TI - Endovascular grafting for the treatment of abdominal aortic aneurysms. AB - Endovascular repair of an aortic aneurysm will allow aneurysm exclusion using a graft passed inside the aorta either percutaneously or from a small groin incision. Morbidity and mortality associated with this procedure should be decreased considerably. The first grafting systems currently being developed will be appropriate for repair of aneurysms of the abdominal and descending thoracic aorta that can be repaired using tube grafts. Several research groups have shown that endovascular grafting of the aorta can be accomplished successfully. PMID- 1496446 TI - Endovascular therapy of venous thromboembolic disease. AB - This article discusses the background and status of inferior vena caval filtration and transvenous catheter techniques for pulmonary embolectomy in the management of venous thromboembolic disease. PMID- 1496447 TI - [The hyperfractionated radiotherapy of tumors in the head-neck area]. AB - This paper provides a survey on investigations that deal with the effects of hyperfractionation. The influence of relevant parameters on treatment results is explained. Furthermore, clinically practicable hyperfractionated treatment schedules for therapy of head and neck tumours are proposed. Clinical and experimental reports reveal that with hyperfractionation two strategies can be realised: 1. Late normal tissue reactions can be reduced without changing total dose. In this case local tumour control rate remains unchanged. 2. To enhance tumour control rates a higher total dose can be administered, if late reactions were dose limiting in the reference schedule. In this case a reduced dose per fraction and an appropriately increased total dose will leave late reactions unchanged. Applying two fractions per day the dose per fraction should not exceed 1.4 Gy. Otherwise severe acute reactions could require treatment interruption. A time interval of at least six hours between fractions reduces the risk of acute and late reactions considerably. PMID- 1496448 TI - Radiation therapy of para-aortic lymph nodes in gynaecologic cancers: techniques, results and complications. AB - From 1965 to 1986 the para-aortic lymph nodes of 141 patients with gynaecologic cancers were irradiated directly after initial treatment of the primary site was completed. Another 32 patients only received para-aortic radiation treatment when para-aortic metastases became clinically apparent some time later. Radiation therapy was performed using a biaxial-four-segmental-rotating-field-technique. Crude survival of the group with initial para-aortic radiation treatment is far better than of the second group. Only five cases of severe complications due to para-aortic treatment were reported. In order to analyze the reason for such a low number of complications, CT-treatment planning for a typical patient was performed for different methods as they have been described in the literature, also referring to treatment data such as success, total dose and dose distribution, thus influencing the complication rate. Obviously, the biaxial-four segmental-rotating-field-technique is a method allowing to deposit a certain dose into the target volume without considerably damaging tissues in the vicinity. PMID- 1496449 TI - [The importance of axillary diagnosis in breast cancer from the viewpoint of radiotherapists. The results of a retrospective study of 671 patients]. AB - We reviewed the clinical evolution and survival of 671 post mastectomy breast cancer patients. 561 patients underwent a postoperative radiotherapy, whereas 110 did not. After grouping for N0 and N+, the median number of examined axillary lymph nodes in the not irradiated group was for N0 status three and for the N+ status eight axillary lymph nodes. In the latter group the median number of the involved axillary nodes was three. In the post mastectomy irradiated N0 group the median number of examined axillary nodes was five, whereas in the N+ group the corresponding number was seven. The median number of involved nodes was two. The majority of the N0 patients who were not postoperatively irradiated were referred to our clinic with a local recurrence. The study shows that axillary staging of the N0 group was not performed corresponding to the today's accepted oncological norms for the minimum number of axillary nodes to be examined to determine a "true" N0 axillary status. Thus, it was not a surprise to find out, for N0 patients, a dependency of the survival rate on the number of examined axillary nodes. Patients with more than nine examined nodes showed better survival rates than patients with less than five examined nodes (p less than 0.05). The irradiation of the axilla is obligatory in case of incomplete axillary dissection (less than ten negative examined nodes from level I and II and less than 18 nodes for a positive axillary dissection). The irradiation of the axilla is not indicated after a complete axillary clearance. PMID- 1496450 TI - Determination of virtual SSDs for electron beams from a dual energy linear accelerator. AB - Electron beams from an accelerator appear to originate from a point away from the vacuum window designated as virtual source. Virtual source to isocenter distances are determined experimentally by measurements in a polystyrene phantom with inverse square law method. Corrections required for percentage depth dose are also determined. Results of our study are compared with that of other investigators. PMID- 1496451 TI - Chromosome aberrations induced in human lymphocytes by U-235 fission neutrons. Part II: Evaluation of the effect of the induced Na-24 activity on the chromosomal aberration yield. AB - Blood samples were spiked with Na-24 to study the separate effect of this nuclide on the incidence of chromosomal aberrations in neutron irradiated blood samples. A delay of 96 h was allowed before cultivation, so the results of chromosomal aberration analysis could be compared with the results obtained by direct irradiation of blood samples with U-235 fission neutrons [7]. The absorbed dose was calculated using a simple conservative model. From the results obtained we can conclude that Na-24 alone was not the reason for the difference in the incidence of chromosomal aberrations between blood samples cultivated immediately after "in vitro" irradiation by U-235 fission neutrons and samples which were cultivated after 96 h storage. PMID- 1496452 TI - [Acute and chronic disorders in gastric emptying after the x-ray irradiation of the rat stomach and their therapeutic modification]. AB - After localized 300 kV X-irradiation of the rat stomach the stomach emptying time of a liquid and a solid test meal was examined with a non-invasive radiological method. In the acute period one to three weeks after irradiation with single doses between 10.7 and 21.3 Gy we observed a faster emptying of the liquid and a delayed emptying of the solid test meal. The faster emptying of the liquid test meal was treated successfully with atropine. In the chronic period we observed a delayed emptying of the liquid and of the solid test meal. These emptying disorders were treated partially successfully with the parasympathomimeticum carbachol and they were treated completely successfully with the dopamine antagonist metoclopramide. PMID- 1496453 TI - [Plasma-membrane fluidity studies of murine neuroblastoma and malignant melanoma cells under irradiation]. AB - Murine neuroblastoma (C-1300 NMB) and malignant melanoma (B16) cells were radiated in presence of radiopharmaceutics. Sensibilization was carried out with BSO and protection with TMX. Changes in fluidity of the plasma membrane, in cellular GSH contents and cell cycle were observed. After radiation fluidity of the plasma membrane is increased, whereas intracellular GSH decreased. These changes were intensified by BSO and reduced by TMX. Fluidity of the plasma membrane correlates with intracellular GSH and also with cell cycle. It is suggested that changes in plasma membrane fluidity can be used as an additional parameter for the determination of sensitivity towards radiation. PMID- 1496454 TI - Megavoltage grid total body irradiation of C3Hf/SED mice. AB - The effect of a grid on whole-body megavoltage radiation tolerance in C3Hf/SED mice was studied. Adult mice were irradiated beneath a 50% megavoltage grid. LD50 (50% lethality) values were measured at ten and 30 days. LD50/30 day increased by a factor of 1.5 for mice receiving both single and two fraction irradiation beneath the grid. LD50/ten day increased by factors of 1.1 to 1.2 for single, two, and five fraction irradiation beneath the grid. PMID- 1496455 TI - Radioprotection of spleen by a combination of 5-hydroxy-L-tryptophan and 2 aminoethylisothiuronium bromide hydrobromide in lethally irradiated rats. AB - Radioprotective efficiency of the combination of 5-hydroxy-L-tryptophan (5-HTP, 100 mg/kg) with 2-aminoethylisothiuronium bromide hydrobromide (AET, 20 mg/kg) in protecting splenic tissue following 8 Gy whole-body gamma radiation (WBGR) has been studied in adult male Sprague Dawley rats. Loss in splenic weight, splenic cells and DNA was observed following & Gy WBGR, which was modified significantly in 5-HTP+AET (ip) pretreated group. The study further showed that pre-treatment with this formulation led to an increased superoxide dismutase (SOD) activity and a decrease in lactate/pyruvate ratio in the cytosol fraction of the spleen. PMID- 1496456 TI - Caries experience in teenagers related to changes in a dental health programme. AB - Comparisons were made of the number of approximal DF-surfaces radiographically recorded at the ages of 13 and 16 years between two groups of children, born in 1964 and 1971, respectively. The aim of the study was to examine if the differences in caries prevalence could be related to the effects of the changes in the dental health programme with time in Goteborg, Sweden. The caries prevalence at 16 years of age was significantly lower in the 1971 group. This was mainly due to a decrease in the number of fillings and caries lesions in girls. However, no statistically significant differences were found between the groups with regard to the mesial surfaces of the first permanent molars. In comparisons between the 20 per cent of children of both sexes with most caries, the 1971 group presented significantly lower DF-values at 16 years of age. The children in the 1971 group had a lower age at the start of organized dental care, had had more topical fluoride applications and, especially the girls, had probably used fluoride dentifrices more frequently. These factors, taken singly as well as in combination, are presumed to have contributed to the lower caries prevalence in the 1971 group. PMID- 1496457 TI - The castability of unalloyed titanium in three different casting machines. AB - The general demand for a variety of fine detail work made of titanium has resulted in the development of equipment/systems for the casting of this metal. Dental casting machines suitable for the casting of titanium are now also available. The aim of the present study was therefore to evaluate the possibility of precision casting of dental crown restorations of unalloyed titanium. The three kinds of casting equipment currently used in Sweden were tested by evaluating the crown edge diameter of 10 titanium crowns processed by each one of the titanium casting machines. The results revealed that clinically acceptable margins can be obtained but also that further improvements in processing have to be achieved before titanium casting can be considered as uncomplicated as the casting of traditional dental gold alloys. PMID- 1496458 TI - Base plate wax, dimensional stability and sorption of active components following treatment with disinfectant solutions. AB - The influence of seven disinfectants on the dimensional stability of a base plate wax, Tenax, was studied. Two methods for treatment were tested - immersion for one hour and spraying respectively. After spraying no significant influence on the wax could be established and after immersion four of the seven disinfectants, including Cidex and K-644, likewise had no significant influence on the dimensional stability. The wax specimens did not show any significant weight increase (less than one per cent) after immersion for four days but in four disinfectant solutions the surface properties of the wax specimens had changed showing that active components of the disinfectants were absorbed into or adsorbed on the wax surface. PMID- 1496459 TI - Amalgam, composite resin and glass ionomer cement in Class II restorations in primary molars--a three year clinical evaluation. AB - Amalgam (ANA 2000), composite resin (Occlusin), and glass ionomer cement (ChemFil) were compared in conventional Class II restorations in second primary molars. Twenty-five restorations of each material were placed by two dentists in 50 patients. The restorations were evaluated during a three year period using the USPHS criteria. Great differences could be found between the materials. The failure rate (USPHS ratings Charlie) was after three years 8 per cent for the amalgam, 16 per cent for the composite resin and 60 per cent for the glass ionomer cement restorations. PMID- 1496460 TI - Glass ionomer cement used as surgical dressing after radical surgical exposure of impacted teeth. AB - GPA cement was tested as an alternative to conventional surgical dressings in connection with radical surgical exposure of teeth. The material comprised 29 patients (mean age 14 4/12 years) with 35 impacted maxillary canines in palatinal position. Soft tissue and bone covering one fifth to one quarter of the tooth crown were removed. The enamel was cleaned with physiological saline and dried with gauze pads. Ketac-Fil was applied using the ESPE Aplicap system. Application stopped when the level of intact mucosa was reached. At control after 1-2 weeks (35 teeth) all packs were in place. Healing conditions were normal and soft tissue regrowth was not seen. At control after 1-6 months (23 teeth) 10 dressings were in place. Surrounding mucosa was healthy regardless of the presence of absence of pack. Soft tissue regrowth was not seen. 6-16 months postoperatively (12 teeth) all packs except 1 had been lost. Soft tissue regrowth in combination with eruption failure was seen in 2 patients. In these cases the packs had been lost soon after the first control, i.e. before healing had been completed. The results indicate that GPA cement can be recommended as an alternative to conventional surgical dressings in connection with radical surgical exposure of teeth. PMID- 1496461 TI - Pulpal response to restoration of deep cavities with high-copper amalgam. AB - The effect on the pulp of a high-copper amalgam was studied in buccal cavities in 16 pairs of human premolars, 32 teeth, restored with ANA 2000. To minimize the risk of bacterial contamination, the cavities were treated with a cleanser, Tubulicid, and the outer portion of the filling was replaced by zinc oxide eugenol cement (ZOE), i.e. surface-sealing. In one cavity in each pair, the control, a thin lining was used. The teeth were extracted after 5-13 days, sectioned, stained with hematoxylin-eosin or Brown and Brenn and evaluated for the degree of pulpal inflammation and presence of bacteria. The results showed that regardless of whether lining was used or not, no inflammation or only a very few inflammatory cells were found in the 21 teeth in which the thickness of the remaining dentin varied from 0.15 mm to 0.5 mm, except for one pair showing slight to moderate inflammation. However, in this pair bacterial growth were found on the cavity walls. No other teeth showed bacterial growth. In the remaining eleven teeth the thickness of the remaining dentin was less than 0.08 mm, including five pulpal exposures. Slight to severe inflammation occurred in eight of these teeth. ANA 2000 per se did not seem to irritate the pulp except in very deep cavities or on direct exposures. The reason for this reaction is not known, but it might be attributable to the zinc content of the amalgam. PMID- 1496463 TI - [Executive Board. Cooperation about working environment. Continued tight budget management. One for all]. PMID- 1496462 TI - [Nursing under Nazism. A revolt]. PMID- 1496465 TI - [Unemployment insurance--every 5th nurse receives money from the unemployment insurance]. PMID- 1496464 TI - [History: searching in cellars and depots]. PMID- 1496467 TI - [The good work--a tour de force]. PMID- 1496466 TI - [Unemployment insurance--new rules about compensation from unemployment insurance]. PMID- 1496468 TI - [Nursing under Nazism. They beat patients to death]. PMID- 1496469 TI - [Nursing under Nazism. They broke away]. PMID- 1496470 TI - [Clinical development--super nurses]. PMID- 1496471 TI - [History--health care's part of history]. PMID- 1496472 TI - [UNICEF--children's New World order]. PMID- 1496473 TI - [Into the heat]. PMID- 1496474 TI - [Drug information: garlic is healthy--but the jungle of preparations is dense]. PMID- 1496475 TI - [Florence Nightingale--"barracks" were a residence]. PMID- 1496476 TI - [Nursing care--thoughtfulness a commodity in short supply]. PMID- 1496478 TI - [Patient information--an inspiring catalog]. PMID- 1496477 TI - [Nicaragua--from knowledge to action]. PMID- 1496479 TI - [Private hospital--close to ideal]. PMID- 1496480 TI - [Private hospital--key word: planning]. PMID- 1496481 TI - Agenda on AIDS. PMID- 1496482 TI - Information must be provided prior to vaccine administration. PMID- 1496483 TI - The breaks of the game. Sports medicine in Texas. PMID- 1496484 TI - AIDS: to test or not to test. PMID- 1496485 TI - More bills filed to correct GPCI problems. PMID- 1496486 TI - TMA delegates act on tax credits, drunken driving, other legislative issues. PMID- 1496487 TI - TMA house grapples with CME, licensure issues. PMID- 1496488 TI - Improvements in Medicaid program make it easier to participate. PMID- 1496489 TI - TMA persists in struggle to ease 'regulatory overload'. PMID- 1496490 TI - An outpatient-focused program for childhood diabetes: design, implementation, and effectiveness. AB - Treatment of childhood diabetes mellitus has undergone many recent changes, one of which is an increasing focus on outpatient management. In mid-1988, the pediatric diabetes clinic at Texas Children's Hospital began adopting an outpatient-focused treatment program using a care team. This report reviews our experience during this transition. Between 1987 and 1990, the percentage of new onset patients who were never admitted to the hospital increased from 0 to 38%. Length of stay for new-onset patients who are admitted has declined. The shift in program focus has also led to decreased diabetes-related readmissions and length of stay per readmission. Estimated total patient cost savings exceed $100,000 per year for new-onset patients alone. Our results regarding patient care and cost effectiveness agree with reports from other such diabetes treatment programs and support greater acceptance and use of this outpatient-focused approach. PMID- 1496491 TI - "Educating" the person with diabetes in an ambulatory setting. PMID- 1496492 TI - Even inert chemicals in pesticides can cause harm. PMID- 1496493 TI - Medicaid improvements worth notice. PMID- 1496494 TI - Byssinosis--a form of occupational asthma? PMID- 1496495 TI - Inhaled corticosteroids: benefits and risks. PMID- 1496496 TI - Poorly perceived asthma. PMID- 1496497 TI - Reduced subjective awareness of bronchoconstriction provoked by methacholine in elderly asthmatic and normal subjects as measured on a simple awareness scale. AB - BACKGROUND: Asthma death rates are rising, with the greatest rise and highest death rates in old age. A reduced cardiovascular response in the elderly may lead to the underestimation by physicians of the severity of acute asthma attacks. This would be compounded if elderly patients had reduced awareness of bronchoconstriction. METHODS: Methacholine provoked bronchoconstriction was compared in 34 elderly (17 asthmatic, 17 normal; age 60-83, mean 68 years) and 33 young subjects (16 asthmatic, 17 normal; 20-46, mean 30 years). None were smokers. All underwent inhaled methacholine challenge by the Newcastle dosimeter method, monitored by maximal expiratory flow-volume loops (MEFVL). The endpoints were a 35% fall in forced expiratory flow at 50% vital capacity or cumulative inhalation of 6.4 mg methacholine. The one second forced expiratory volume (FEV1) was derived from MEFVL. After challenge and before bronchodilatation subjects graded awareness of respiratory discomfort from 1 (no symptoms) to 4 (pronounced symptoms needing immediate treatment). RESULTS: Despite a greater fall in FEV1 in elderly asthmatic patients (mean (SE) 27.4% (2.2%)) than in young asthmatic patients (21.5% (1.7%)) elderly patients were less aware of bronchoconstriction (awareness score 2.00 (SE 0.15) than young patients (3.06 (0.11)). Similar differences in awareness score were seen between elderly normal subjects (1.53 (0.17)) and young normal subjects (2.76 (0.22)), despite no difference in degree of bronchoconstriction. CONCLUSIONS: Reduced awareness of moderate acute bronchoconstriction in old age may delay self referral in acute asthma and contribute to higher asthma mortality in the elderly. PMID- 1496498 TI - Bone density in asthmatic patients taking high dose inhaled beclomethasone dipropionate and intermittent systemic corticosteroids. AB - BACKGROUND: Asthmatic patients taking low to moderate doses of inhaled topical corticosteroids have been shown to have lower bone density than those taking bronchodilators only. There is little information on bone density in asthmatic patients taking high dose inhaled corticosteroids. METHODS: Bone mass was studied in three age matched groups of asthmatic patients. These comprised: 17 asthmatic patients who had never taken inhaled or systemic corticosteroids (group 1); 20 patients who had taken beclomethasone diproprionate in a dosage of 1000-2000 micrograms daily for at least a year, who had also received courses of systemic corticosteroids in the past (group 2); and 20 patients who were taking both high dose inhaled corticosteroids and regular low dose prednisolone, at a median dose of 7 mg daily (group 3). Vertebral bone density was measured by quantitative computed tomography. Biochemical indices of bone formation and resorption were also measured. RESULTS: Mean bone density in group 2 (127.5(22.6) mg/ml) was similar to that in group 3 (114.5 (36.0) mg/ml). Bone density was significantly lower in both of these groups than in group 1 (160.4 (27.4) mg/ml). There were no significant differences between groups for any of the markers of bone formation and resorption. CONCLUSIONS: Asthmatic patients receiving high dose inhaled beclomethasone and intermittent courses of systemic corticosteroids have reduced vertebral bone density. The bone loss is similar in degree to that seen in patients taking high dose inhaled topical corticosteroids and continuous low dose systemic corticosteroids. PMID- 1496499 TI - Bone turnover during short course prednisolone treatment in patients with chronic obstructive airways disease. AB - BACKGROUND: Although osteoporosis is a well known side effect of long term prednisolone, the effects of a short course are less clear. Biochemical markers of bone turnover were therefore studied in 10 men with chronic obstructive airways disease who required assessment of "steroid reversibility" (mean age 65 years, mean FEV1 1.2 1). METHOD: Patients received, single blind, two weeks of placebo, four weeks of prednisolone 20 mg/day, and then two further weeks of placebo. RESULTS: The mean (SD) fasting urinary hydroxyproline:creatinine ratio, a marker of bone resorption, increased by 65% with prednisolone (from 8.9 (5.7) to 14.7 (8.5) mumol/mmol) and returned to baseline after placebo. Serum alkaline phosphatase, a marker of net bone formation, fell after prednisolone by 28% (from 113 (41) to 81 (30) IU/1). Substantial changes occurred after only two weeks of prednisolone. Serum osteocalcin, calcium, and phosphate concentrations did not change significantly. CONCLUSIONS: Short courses of prednisolone increased bone resorption and inhibited bone formation after two and four weeks. PMID- 1496500 TI - Can lung function measurements be used to predict which patients will be at risk of developing interstitial pneumonitis after bone marrow transplantation? AB - BACKGROUND: Lung function often deteriorates after bone marrow transplantation for haematological malignancies. Whether pulmonary function measurements are useful for monitoring patients' progress after transplantation and for alerting clinicians to the development of pneumonitis is uncertain. METHODS: Serial pulmonary function measurements were made in 39 patients with a haematological malignancy, and the values from 18 recipients of T cell depleted allogeneic (n = 17) or autologous (n = 1) bone marrow transplants who developed interstitial pneumonitis were compared retrospectively with values from 21 recipients of allogeneic (n = 17) or autologous (n = 4) transplants who did not develop pneumonitis. Lung function was measured at the onset of a further 18 episodes of pneumonitis. RESULTS: Measurements made before transplantation showed no difference in forced expiratory volume in one second (FEV1), transfer factor for carbon monoxide (TLCO), or total lung capacity between the two groups, but the forced vital capacity (FVC) was slightly higher in those who developed pneumonitis (mean (SD)% predicted 104 (12)) than in those who did not (93 (17%)). Six weeks and three months after transplantation all pulmonary function measurements had fallen slightly in both groups but TLCO had fallen considerably more in those who later developed pneumonitis, being 71% (SD 11%) and 77% (7%) of pretransplant values in patients who later developed pneumonitis compared with 109% (38%) and 96% (26%) in those who did not. All lung function measurements were significantly lower at the onset of pneumonitis than three months after transplantation, even in patients with no abnormal signs and a normal chest radiograph. CONCLUSIONS: Serial measurements of gas transfer before and after bone marrow transplantation may be useful for predicting which patients will be at risk of developing pneumonitis and may help to diagnose pneumonitis in breathless patients with no abnormal signs. PMID- 1496501 TI - Extrapulmonary sites of Pseudomonas aeruginosa in adults with cystic fibrosis. AB - BACKGROUND: Pseudomonas aeruginosa infection is seldom eradicated in patients with cystic fibrosis despite intensive antipseudomonal treatment. Upper airway sites of infection may contribute to perpetuation of lower airways infection. This study was designed to find out which extrapulmonary sites are infected and whether the strains at these sites are identical to those in the lungs. METHODS: Sputum and upper airway samples from 42 patients were cultured for P aeruginosa and stool samples from 20 patients were also tested. Nineteen isolates from sputum and extrapulmonary sites from four patients were genotyped with the pCM tox probe. RESULTS: P aeruginosa was isolated from the sputum of 36 patients, 34 of whom had infection in the upper airways. Six of the 20 patients tested were positive for P aeruginosa in the stool. The nasopharynx was colonised in 30 patients, the oropharynx in 29, the middle meatus in 13, the external nares in six, and the inferior turbinate in four. Three of four patients tested had the same strain of P aeruginosa (a different one in each individual) in the sputum and the upper airways, and in two of the three the stool isolate was a different strain. CONCLUSION: Most adults with cystic fibrosis and P aeruginosa pulmonary infection have upper airway reservoirs of the organism and strains from these sites are identical to those in the lungs. PMID- 1496502 TI - Interpretation of bronchodilator response in patients with obstructive airways disease. The Dutch Chronic Non-Specific Lung Disease (CNSLD) Study Group. AB - BACKGROUND: There is no agreement on how a bronchodilator response should be expressed. Ideally, the index used should be able to distinguish asthma from chronic obstructive lung disease and be independent of initial FEV1. METHODS: Two hundred and seventy four adults (aged 18-60 years) outpatients with obstructive airways disease were studied. Patients were divided into syndrome groups on the basis of a standardised history: asthma (n = 99), asthmatic bronchitis (n = 88), and chronic obstructive lung disease (n = 51); 36 subjects could not be attributed to any subgroup. FEV1 was measured before and 20 minutes after inhalation of 1000 micrograms terbutaline. Different expressions of bronchodilator response (delta FEV1) were compared with respect to their dependence on initial FEV1 and their efficacy in separating subjects with asthma from those with chronic obstructive lung disease. delta FEV1 was expressed as a percentage of initial FEV1 (delta FEV1%init), absolute value (delta FEV1[1]), percentage of predicted FEV1 (delta FEV1%pred), standardised residual (delta SR FEV1), and percentage of maximal possible increase (delta FEV1%[pred-init]). RESULTS: delta FEV1%init was more dependent on initial FEV1 (p = -0.405) than delta FEV1[1] (r = -0.145), delta FEV1%pred (r = -0.166), and delta SR-FEV1 (r = 0.127). delta FEV1%[pred-init] reached infinity when initial FEV1 approached predicted levels. delta FEV1%pred had a higher likelihood ratio (1.71) for separating patients with asthma from those with chronic obstructive lung disease than other expressions of bronchodilator response. Asthmatic patients had larger mean bronchodilator responses than patients in other subgroups; this difference was largest for delta SR-FEV1 (F = 9.19) and delta FEV1%pred (F = 9.03); it was much smaller for delta FEV1%init (F = 5.89). Despite significant differences in mean response, there was a large overlap of individual responses between diagnostic subgroups. The bronchodilator response was continuously and unimodally distributed for all expressions. CONCLUSIONS: delta FEV1%pred appears to be the most useful method of expressing bronchodilator response, both for clinical and for research purposes. Reversibility of airways obstruction in response to a bronchodilator is a continuous variable and not a dichotomous triat. Any cut off level of a "positive" bronchodilator response is therefore arbitrary. PMID- 1496503 TI - Intra-alveolar macrophage numbers in current smokers and non-smokers: a morphometric study of tissue sections. AB - BACKGROUND: The alveolar macrophage is believed to be important in the defence of the lung and possibly in the pathogenesis of lung disease. Cell counts in bronchoalveolar lavage fluid have suggested that smokers have an increased number of alveolar macrophages but have not enabled the number to be related to a measure of lung structure. METHODS: The number of alveolar macrophages was counted in histological sections from lung resection specimens from a group of smokers and non-smokers. The results were related to a measurement of lung structure obtained by means of an automated morphometric technique and expressed in terms of units of lung volume or of lung surface area. RESULTS: The smokers had a significantly increased number of alveolar macrophages per unit lung volume and per unit surface area, through the relative increase was less than has appeared from bronchoalveolar lavage studies. When smokers and non-smokers with similar lung structure were compared the smokers had more alveolar macrophages, indicating that smoking and not loss of lung structure is responsible for the increase. CONCLUSIONS: Smokers had more alveolar macrophages than non-smokers when the number was expressed quantitatively with respect to the underlying architecture. Changes in cell populations postulated to be important in the pathogenesis of disease within the lung should be related to lung architecture because this may vary considerably between individuals. PMID- 1496504 TI - A mask to modify inspired air temperature and humidity and its effect on exercise induced asthma. AB - BACKGROUND: Heat and moisture loss from the respiratory tract during exercise are important triggers of exercise induced asthma. METHODS: A new heat and moisture exchange mask has been developed which both recovers exhaled heat and water and has a sufficiently low resistance for use during exercise. The effect of the mask on inspired air temperature was studied in four normal subjects. Eight asthmatic subjects performed identical exercise protocols on three separate days, breathing room air through a conventional mouthpiece, a dummy mask, and the new heat and moisture exchange mask. Seven different asthmatic subjects exercised while breathing cold air at -13 degrees C through a dummy or active mask. RESULTS: All subjects found the new mask comfortable to wear. The mean inspired temperature when the mask was used rose to 32.5 (1.4) degrees C when normal subjects breathed room air at 24 degrees C and to 19.1 (2.7) degrees C when they inhaled subfreezing air at -13 degrees C. The heat and moisture exchange mask significantly reduced the median fall in forced expiratory volume in one second (FEV1) after exercise to 13% (range 0-49%) when asthmatic subjects breathed room air compared with 33% (10-65%) with the dummy mask and 28% (21-70%) with the mouthpiece. The fall in FEV1 when the asthmatic subjects breathed cold air was 10% (0-26%) with the heat and moisture exchange mask compared with 22% (13-51%) with the dummy mask. CONCLUSION: Use of a heat and moisture exchange mask can raise the inspired temperature and humidity and ameliorate the severity of exercise induced asthma. The mask may be of practical value in non-contact sport or for people working in subzero temperatures. PMID- 1496505 TI - Effect of carbohydrate rich versus fat rich loads on gas exchange and walking performance in patients with chronic obstructive lung disease. AB - BACKGROUND: High calorie intakes, especially as carbohydrate, increase carbon dioxide production (VCO2) and may precipitate respiratory failure in patients with severe pulmonary disease. Energy obtained from fat results in less carbon dioxide and thus may permit a reduced level of alveolar ventilation for any given arterial blood carbon dioxide tension (PaCO2). METHODS: Ten patients with stable severe chronic obstructive lung disease underwent a six minute walk before and 45 minutes after taking 920 kcal of a fat rich drink, an isocalorific amount of a carbohydrate rich drink, and an equal volume of a non-calorific control liquid on three separate days, in a double blind randomised crossover study. Borg scores of the perceived effort to breathe were measured at the beginning and end of each six minute walk. Minute ventilation (VE2), VCO2, oxygen consumption (VO2), respiratory quotient (RQ), arterial blood gas tensions, and lung function were measured before and 30 minutes after each test drink. RESULTS: Baseline measurements were similar on all three test days and the non-calorific control drink resulted in no changes in any of the measured variables. The carbohydrate rich drink resulted in significantly greater increases in VE, VCO2, VO2, RQ, PaCO2, and Borg score and a greater fall in the distance walked in six minutes than the fat rich drink (mean fall after carbohydrate rich drink 17 m v 3 m after fat rich drink and the non-calorific control). The increase in VCO2 correlated significantly with the decrease in six minute walking distance and the increase in Borg score after the carbohydrate rich drink. The only significant change after the fat rich drink when compared with the non-calorific control was an increase in VCO2. CONCLUSIONS: Comparatively small changes in the carbohydrate and fat constitution of meals can have a significant effect on VCO2, exercise tolerance, and breathlessness in patients with chronic obstructive lung disease. PMID- 1496506 TI - Ultrasound guided percutaneous cutting biopsy for the diagnosis of pulmonary consolidations of unknown aetiology. AB - BACKGROUND: Ultrasound has been used to guide percutaneous aspiration biopsy of thoracic tumours with high diagnostic yield. This study assessed the diagnostic value of ultrasound guided percutaneous cutting biopsy for pulmonary consolidation of unknown aetiology. METHODS: Thirty patients with undiagnosed lobar or segmental consolidation underwent ultrasound guided percutaneous needle aspiration and large bore cutting biopsy. The needle aspirates and biopsy specimens were sent for cytological, microbiological, and histopathological examination. RESULTS: Percutaneous needle aspiration provided a diagnosis in nine of 30 patients (30%), whereas cutting biopsy obtained a satisfactory specimen for histological diagnosis in 28 patients (93%) and provided a definite aetiological diagnosis in 17 patients (57%). The combination of needle aspiration with Trucut biopsy provided a diagnostic rate of 63%. The underlying diagnoses were fungal pneumonia (five patients), tuberculosis (five), bacterial pneumonia (one), bronchioloalveolar carcinoma (three), lymphoma (two), adenocarcinoma (one), vasculitis (one), acute pneumonia of unknown aetiology (one), and chronic non specific pneumonia (nine). Two patients, who had necrotic tissue only in the biopsy specimen, were found at thoracotomy to have an adenocarcinoma and aspergillosis. Two patients had complications from the technique, a small pneumothorax in one and a small haemoptysis in another. CONCLUSIONS: Ultrasound guided percutaneous cutting biopsy is a valuable method for diagnosing pulmonary consolidation of unknown aetiology. The diagnostic yield is high and the procedure appears to be relatively safe. PMID- 1496507 TI - Randomised clinical trial of chest drainage systems. AB - BACKGROUND: Problems in the management of thoracic trauma have stimulated the search for an alternative to underwater seals for drainage of the pleural cavity. A chest drainage bag incorporating a one way flutter valve has been compared with underwater seal drains in a randomised clinical trial. METHODS: During June December 1989 119 patients undergoing elective thoracotomy were randomised to receive postoperative chest drainage by drainage bags (56 patients, 87 drains) or by underwater seal drains (63 patients, 98 drains). Daily drainage volumes, the requirement for pleural suction, mobility, and complications were recorded prospectively. RESULTS: There was no significant difference between the two groups in the mean volume drained, the requirements for pleural suction, or the occurrence of complications. Patients with drainage bags were fully mobile 23 hours (95% confidence interval 0-47 hours) earlier than the others. CONCLUSIONS: When used after elective thoracotomy drainage bags are safe and effective and permit earlier mobility than underwater seal drains. PMID- 1496509 TI - Medium dose rate endobronchial radiotherapy with caesium-137. PMID- 1496510 TI - Cocaine induced eosinophilic lung disease. AB - A patient developed fever, bronchoconstriction, hypoxaemia, pulmonary infiltrates, and serum and bronchoalveolar lavage fluid eosinophilia on two occasions after inhaling crack cocaine. Transbronchial biopsy specimens showed normal lung parenchyma but a dense eosinophilic infiltrate within the bronchial wall. Both episodes resolved promptly after treatment with corticosteroids. Eosinophilic lung disease may be a steroid responsive complication of crack cocaine abuse. PMID- 1496508 TI - Nosocomial pneumonia in the intensive care unit: mechanisms and significance. PMID- 1496511 TI - Retroperitoneal silicosis mimicking pancreatic carcinoma in an Alpine miner with chronic lung silicosis. AB - A miner, known to have had lung silicosis for 30 years, was investigated for abdominal pain. A retroperitoneal mass was found, in which histological examination showed an inflammatory reaction to silica. PMID- 1496512 TI - Aeromonas hydrophila fulminant pneumonia in a fit young man. AB - A previously healthy 24 year old athletic man became ill suddenly with pneumonia the day after swimming in the sea. Despite intensive support measures in the intensive care unit he died three hours after admission and 21 hours after his first symptom. Necropsy showed bilateral haemorrhagic necrotising pneumonia. Aeromonas hydrophila was isolated from a blood culture taken at admission and from the lungs at necropsy. The infection may have come from contaminated sea water. PMID- 1496513 TI - A 10 year follow up of 180 adults with bronchial asthma: factors important for the decline in lung function. PMID- 1496514 TI - Achilles tendon rupture: an underrated complication of corticosteroid treatment. PMID- 1496515 TI - [The clinical case. Cystoid (type A) in the medial condyle of the bony femur on both sides]. PMID- 1496516 TI - [The legal status of homeopathic medicines. Quality requirements, registration and permit procedures]. AB - Homeopathic medicaments which are ready for application have to be approved or registered before they can be made available. This procedure is regulated by the "Arzneimittelgesetz (AMG)", a law regulating licensing and registration of medicaments. The commission in charge of the registration and licensing of homeopathic medicaments is the "Aufbereitungskommission D" of the German "Bundesgesundheitsamt (BGA)", the Board of Public Health. Application forms are dealt with on the basis of controlled and non-controlled clinical studies, application observations, and case studies, as well as specialized literature. The commission is trying to do justice to the particular features of the special field of homeopathy. PMID- 1496517 TI - [Estrogen antagonists in the dog]. PMID- 1496518 TI - [Necessary care of newborn lambs using ovine colostrum. 2. Duration of administration]. AB - Sheep colostrum, pooled from 0-12 h milkings, was fed to 38 newborn lambs for either 6, 12, 18 or 24 hrs after birth. The influence of the duration of feeding periods on the transintestinal passage of immunoglobulins, the growth performance, the loss rate and the onset of immunoglobulin synthesis were investigated by monitoring the serum concentrations of IgG1, IgG2, IgM and IgA during months 1 through 9 of life. Feeding of 3 portions of 100 ml at 2 h intervals resulted in lower serum levels of Ig's than the extension of the feeding to 12 x 100 ml every second hour. There was, however, no difference in the onset of endogenous Ig production between both groups. Growth performance and the loss rate were also identical. PMID- 1496519 TI - [The selenium content in the blood of newborn sheep and goats--equally contributing to the effect of supplemental oral selenium as a prophylaxis]. AB - The article is based on the analysis of selenium concentration in blood plasma of 9 goats and their kids (n = 17), from two different places, as well as of 12 sheep and their lambs (n = 19) from several flocks. The selenium concentration was measured using ASS. In addition, the activity of CK was determined enzymatically. There was a low plasma selenium level in lambs and goat kids immediately post-natal depending on the selenium state of the mothers. After application of vitamin E and selenium to a group of lambs their selenium levels increased remarkably over 24 hours. Ten days later the average selenium concentration in the plasma of those animals that had been treated was three times as high as that of the control group. It was shown that the absorption of vitamin E and selenium when given orally to newborn lambs is comparable with the absorption after parenteral application, and that a significant increase of the plasma selenium level is attainable by oral application. PMID- 1496520 TI - [Symptoms and course of a parakeratosis outbreak in a boar raising facility]. AB - A case of parakeratosis in pigs due to secondary zinc deficiency (zinc/calcium ratio 0.4 g/100 g; 68.7 mg zinc, 17.1 g calcium per kg food) is reported. Morbidity and symptoms were much more marked in growing boars than in female animals of the same age. In sows the disorder appeared ten days after the first symptoms were seen in the boars. Adult breeding pigs developed no signs of parakeratosis. PMID- 1496521 TI - [Light and electron microscopic studies of Eperythrozoon suis]. AB - A light and electron microscopic study was carried out on pigs experimentally infected with Eperythrozoon (E.) suis during the acute and chronic phase of infection. During the acute phase Eperythrozoon organisms can be recognised by light microscopy as bright to dark orange points or circles. In contrast, in the chronically infected pigs E. suis appear as bright yellow or green small dots on the edge of the erythrocytes or in the plasma. By scanning electron microscopy, immature, juvenile and mature forms of E. suis could be seen on the same erythrocyte during the acute phase. In chronically infected pigs ring-shaped, rounded resting-stage forms, measuring about 1 micron in diameter, can be observed. PMID- 1496522 TI - [Skin and plumage changes in domestic birds. II. Plumage changes]. AB - The study describes plumage modifications and specific feather malformations, as related to the domestication process of different poultry species. The modifications include naked necks, leg feathering, frizzle feathering, silky feathering, fat quills, and feather abnormalities caused by behavioural hypertrophies. Most of these plumage modifications correspond to the breed standard for exhibition poultry fancy. However, they impair the normal function of these animals. The negative influences comprise disorders in social behaviour, loss of typical plumage functions and disabilities of normal mobility, as well as genetic defects and pathogenic predispositions. PMID- 1496523 TI - [Two rare lens abnormalities in horses]. AB - Coloboma and ectopia of the crystalline lens are rarely encountered or diagnosed congenital defects of the equine eye. The clinical and ophthalmoscopic features of a congenital coloboma of the lens in a 3 year old Hanoverian stallion and of an ectopic lens in a 6-month old Hanoverian filly are described and depicted. In the stallion, the lens coloboma was associated with a partial coloboma of the zonules, and in the filly, the ectopic lens was small and spherical (microphakia, spherophakia) and associated with syneresis of and small floaters in the vitreous. Although it cannot be excluded that the ectopic position of the lens may have originated from prenatal uveitis, it was classified as congenital in this case. In both eyes, there were no other clinically detectable congenital defects. PMID- 1496524 TI - [Weak viability syndrome in newborn foals. Retrospective studies of the etiological clarification and chance for recovery]. AB - This review of therapeutic results involved 115 foals with delayed viability syndrome (DVS). The foals were up to four days old. It could be shown that prognosis quoad vitam depended very much on the severity of illness, which could be determined primarily by the foals' ability to stand (SA) and secondly by the presence of the suckling reflex (SR). Those foals that were (still) able to stand -while the suckling reflex was/was not present (anymore) (SA+, SR+; SA+, SR-)- had good prospects of recovery regardless of the causal disease. The chances for survival were significantly poorer if the foals were unable to stand--even if the suckling reflex was still present and especially if it was not present (anymore) (SA-, SR+; SA-, SR-). Glucose and IgG levels were measured following hospitalization and proved to be excellent prognostic indicators, no matter what the causal disease. DVS can vary in severity, but symptoms are rather non specific. Non-infectious causes for DVS were--at a ratio of approximately 3 to 1- significantly more common than primarily infectious causes. The latter--except for diarrhoea--carried a very poor prognosis. PMID- 1496525 TI - [Multiple myeloma/plasmacytoma in a young dog]. AB - A multiple myeloma in an unusually young Cairn terrier (13 months, female) is described. Radiographically, pelvic tumor masses and characteristic systemic osteolysis were found at the end of the 4 week disease course. Therapeutic attempts were hopeless at this stage of the disease, but a form of chemotherapy is recommended. PMID- 1496526 TI - [Fauna and incidence of endoparasites in kittens and their mothers from different husbandry situations in south Germany]. AB - In this epidemiological study 100 litters of Southern Germany were investigated. 70 litters were kept on farms and 30 litters originated from mother cats kept indoors. At least 9 species were detected in litters from farms, 77.1% of these litters were infected with T. cati, 1.4% with hookworms, 10% with Capillaria, 10% with H. taeniaeformis, 67.1% with I. felis, 48.6% with I. rivolta, 17.1% with Toxoplasma/Hammondia, 4.3% with C. parvum and 1.4% with Giardia. In litters kept indoors only 5 species were established. 3.3% were infected with T. cati, 46.6% with I. felis, 33.3% with I. rivolta, 6.6% with Giardia and 3.3% with C. parvum. Analogous differences as regards to the keeping conditions existed also for the mother cats. PMID- 1496527 TI - [The therapy of chronic diseases of the respiratory tract in dogs and cats]. AB - Chronic conditions of the respiratory system are a diagnostic as well as a therapeutic challenge to the veterinarian. In the majority of cases the protective structures, e.g. the vibrating epithelium, have already been irreversibly damaged, so that therapy can only relieve the trouble, but not lead to a full recovery. Prior to initiating a long-term therapy that requires a lot of patience from the veterinarian as well as the owner, it is therefore crucial to carry out a thorough diagnostic procedure. This is a review of the pathophysiological basis and the resulting diagnostic consequences of chronic diseases of the respiratory system. A few selected cases are discussed and recommendations for medical treatment are given. PMID- 1496528 TI - [Reptiles as patients in veterinary practice]. AB - Important diseases of reptiles are described with references to the diagnostic material and patients of the Institute of Zoology and Hydrobiology between 1984 and 1990. The commonest causes of mortality were pneumonia, parasites and poor husbandry. Problems associated with the increasing popularity of reptiles as pets, and appropriate treatments are discussed. PMID- 1496529 TI - [Use of the Reflotron system for the determination of creatine kinase (CK) in the blood of swine, sheep, cattle, horses and dogs]. AB - The Reflotron-CK test was evaluated with blood samples of healthy and diseased pigs, sheep, cattle, horses and dogs in relation to the standard CK-NAC test (UV method). The precision within the series on the day of blood sampling was better than VK = 7.5% (coefficient of variation) with both methods. The day to day precision was estimated by using deep frozen plasma and was in the same order of magnitude with the Reflotron-CK and the UV-method (CV less than 10%). While fresh whole blood of sheep, cattle, horses and dogs respectively should be applied directly onto the dry reagent carrier with the Reflotron-pipette (32 microliters), the blood samples of pigs must be diluted (200 microliters 0.9% NaCl-solution and 32 microliters blood, factor 7.25) before determination with Reflotron-CK. In the five species mentioned the correlation between Reflotron-CK and CK values obtained with the standard UV-method was satisfactory (r greater than 0.96). Systemic deviations of the Reflotron-CK values should be corrected by calculation formulae, given in the paper. PMID- 1496530 TI - Optimal timing of administration of a free radical scavenger in lung preservation. AB - The optimal timing of administration of free radical scavengers in lung preservation has yet to be determined. In previous studies, the oxygen free radical scavenger dimethylthiourea (DMTU) has improved pulmonary function when added to Eurocollins flush solution at the time of lung harvest and infused at the time of lung reimplantation. To determine when DMTU must be administered in order to preserve lung function most effectively, 16 dogs underwent lung allotransplantation. Donor lungs were flushed with modified Eurocollins solution (50 ml/kg) and stored for 12 hr at 4 degrees C. DMTU was either added to the flush solution (5 g) or infused (20 g over 2 hr) at the time of reimplantation. Investigators were blinded to the time of DMTU administration. The contralateral pulmonary artery was ligated after a 1-hr stabilization period. Measurements were recorded for 8 hr while keeping FiO2 constant at 40%. The flush group demonstrated significantly improved survival and oxygenation compared with the infusion group. The mortality rate was 50% in the infusion treatment group, while no deaths occurred in the flush animals. Lung function is adequately preserved after 12-hr storage when DMTU is administered in the flush solution at the time of harvest. It would appear that oxygen free radical scavengers must be present in lung tissue during storage in order to be effective. PMID- 1496531 TI - Evidence of metabolic activity of adult and fetal rat hepatocytes transplanted into solid supports. AB - This study was undertaken to assess the metabolic effect of fetal and adult hepatocyte transplantation in the Gunn rat, genetically incapable of bilirubin conjugation. A comparison was made between fetal and adult hepatocytes transplanted into the spleen, and those injected into polytetrafluoroethylene (PTFE) solid supports that had previously been implanted intraperitoneally. Between 4 and 12 weeks after intrasplenic transplantation of adult liver cells, serum bilirubin was significantly decreased when compared with control animals (39.6 +/- 5.6%; P less than 0.01 vs. controls). Intrasplenic transplantation of fetal hepatocytes resulted in a maximal decrease of 33.2 +/- 9.1% at 8 weeks postoperatively (P less than 0.02 vs. controls). Similar declines of serum bilirubin levels were found after transplantation of adult or fetal liver cells into the solid supports. At 12 weeks after transplantation, bilirubin conjugates were detectable in the bile of all animals that underwent intrasplenic hepatocyte transplantation and in 60% of those that underwent the solid support procedure, whereas none could be detected in control animals. Histological evidence of surviving cells was obtained in all but one animal at 12 weeks, and confirmed at 12 months postoperatively. It is concluded that the PTFE solid support technique offers an attractive alternative to the intrasplenic route, and that both fetal and adult hepatocytes, transplanted in either way still exert their conjugating activity after 12 weeks. PMID- 1496532 TI - Prolonged survival of rat hepatic allografts after total-body irradiation of the donors. AB - The effect of total-body irradiation of the donor on hepatic allograft survival was studied in the rat, with ACI(RT1a) as the donor and LEW(RT1(1)) as the recipient. LEW recipients of ACI liver transplants experienced severe acute rejection, with a mean survival of only 10.2 +/- 0.3 days. The doses of irradiation were 450, 750, and 1000 rads administered 24 hr prior to harvesting or subsequent transplantation. TBI with a dose of 750 rads significantly prolonged the survival of the hepatic allograft to 30.3 +/- 1.7 days, without concomitant immunosuppression. However, neither 450 rads nor 1000 rads of TBI resulted in successful suppression of graft rejection. TBI appeared to have a beneficial effect on hepatic allograft survival and to have no deleterious effect on isograft survival, suggesting a possible modulation of the immunogenicity of the donor organ. Although the cause of this beneficial effect is not clear, TBI with a dose of 750 rads 24 hr prior to organ harvest seems to be optimal to eliminate-antigen presenting cells in the donor organs. PMID- 1496533 TI - Peripheral tolerance of an allograft in adult rats--characterization by low interleukin-2 and interferon-gamma mRNA levels and by strong accumulation of major histocompatibility complex transcripts in the graft. AB - Congenic LEW.1W(RT1.u) heart grafts in LEW.1A(RT1.a) recipient rats are rejected in 15 +/- 6 days. Tolerance (greater than 100 days) can be induced by pretransplant donor-specific blood transfusion. In this case, the graft is not rejected, although it is infiltrated by mononuclear cells specifically cytotoxic, in vitro, against allogeneic donor splenocytes. We studied the expression of MHC class I and class II antigens, IFN-gamma, and IL-2 mRNA in the rejected and tolerated grafts by Northern blotting and in situ hybridization. Our data show that both class I and class II mRNA accumulate in both types of graft, and that class I mRNA accumulation occurs more rapidly in the tolerated grafts. IFN-gamma and IL-2 mRNA accumulate to lower levels and with delayed kinetics in the tolerated grafts compared with the rejected ones, suggesting a role for these lymphokines in the mechanism of rejection/tolerance in this model. This hypothesis is also supported by the observation that IFN-gamma treatment abrogates the induction of tolerance in the recipients receiving pretransplant donor blood transfusion. Furthermore, we observed an uncoupling of the accumulation of IFN-gamma mRNA and of MHC class I and class II mRNA. Our data confirm that the mechanisms of tolerance in this model depend, in part, on alterations of the IL-2/IL-2R pathway of lymphocyte activation but also clearly indicate a decrease of IFN-gamma mRNA accumulation, suggesting that the defect involves several activation molecules. PMID- 1496534 TI - Effects of cyclosporine and corticosteroids on bile secretion in the rat. AB - In order to study their effects on the bile secretion, cyclosporine and methylprednisolone were injected intravenously into rats at a dose of 10 mg/kg b.w. for 30 min. Methylprednisolone had no effect on bile secretion. Cyclosporine led to transient intrahepatic cholestasis characterized by decreased bile flow as well as a decrease of bile salts and cholesterol in bile. Phospholipid levels were not affected. Liver biopsy showed no particular anomaly. These findings suggest that the observed cholestatic reaction may be due to impairment of the metabolism of cholesterol into bile salts or of the conjugation of bile salts rather than to disturbances in bile secretion. After liver transplantation in humans, cholestasis associated with acute rejection or nonspecific cholestasis cannot be attributed directly to the effect of cyclosporine. Cholestasis can be offset by administering taurocholate at a dose of 10 mumol/min/kg b.w. in order to maintain bile salt and phospholipid levels high enough to ensure proper "vectorization" of cholesterol to bile. PMID- 1496535 TI - The effect of donor age on graft survival in pediatric cadaver renal transplant recipients--a report of the North American Pediatric Renal Transplant Cooperative Study. AB - Data from the North American Pediatric Renal Transplant Cooperative Study were analyzed to determine the effect of donor age on graft survival for pediatric recipients of cadaver donor renal transplants. Between January 1, 1987, and November 16, 1990, 787 cadaver donor renal transplants in children less than 18 years of age were registered in the study. The ages of the donors were less than or equal to 5 years in 203 transplants, between 6 and 9 years in 87, between 10 and 39 in 389, and greater than or equal to 40 years in 108. The risk of graft loss was related to donor age by a proportional hazards analysis. The ideal donor age was 20-25 years. The risk of graft loss was increased by both young and old donor age. The risk of graft loss from a neonate donor was 2.7-fold that of the ideal donor, and the risk from a 50-year-old donor was 1.8-fold that of the ideal donor. The relationship between donor age and graft survival was not affected by the age of the recipient. Cold storage time had an added impact on graft survival: grafts with cold storage time greater than 24 hr were 1.5 times more likely to fail than grafts with shorter cold storage time for all donor ages. Analysis of the causes of graft failure revealed that 9.9% of grafts from donors less than or equal to 5 years of age were lost due to vascular thrombosis, primary nonfunction, and other technical causes, compared with 4.6% in 6-9, 4.4% in 10-39, and 2.8% in greater than or equal to 40-year-old donors. We conclude that kidneys from both young and old donors are at increased risk for graft loss, and this increased risk is seen in all recipient age groups. Many of the losses from the young donors--but not older donors--may be due to technical causes. Knowledge of these risks can be used to develop strategies for optimal utilization of kidneys from young and old donors. PMID- 1496536 TI - Mitogen responses of lymphocytes from lung transplant recipients--correlation with rejection and infection. AB - Proliferative responses to nonspecific mitogens were analyzed for 119 bronchoalveolar lavages and 108 concurrent peripheral blood samples from 35 lung transplant patients. The patients were classified at each time as normal, rejecting, or infected on the basis of trans-bronchial biopsy, culture results, clinical signs, and pulmonary function. During rejection episodes the bronchoalveolar lavage responses to concanavalin A and phytohemagglutinin were significantly increased (P less than 0.004 and P less than 0.006, respectively). The differences were less pronounced when rejection occurred within 30 days after bolus immunosuppressive therapy, either as immunoprophylaxis or as treatment for a previous rejection episode, and were not significantly different from normal. Differences in response during rejection were limited to the graft; analysis of circulating T cells was not helpful (P = NS). In contrast, markedly depressed responses to Con A and PHA were seen during infection. Significant differences were observed both in the graft (P less than 0.007) and in circulating lymphocytes (P less than 0.02), suggesting that global depression of mitogen response is associated with immunocompromise. Sequential analysis of 6 patients showed that individual changes in mitogen response paralleled those seen in the population (P less than 0.046, normal vs. rejection and P less than 0.043 normal). These findings suggest that mitogen assays of bronchoalveolar lavage lymphocytes and, to a lesser extent, PBL, are clinically useful in assessing intragraft immunocompetence and in distinguishing rejection from infection in lung transplant patients. PMID- 1496537 TI - Positive crossmatches against mandatorily shared kidneys. AB - From October 1987 through February 1990 approximately 8.5% (29/341) of all donor kidneys shipped under the UNOS Mandatory Sharing Policy were denied to 27 intended recipients due to a positive final crossmatch [XM(+)]. The intended recipients included 18.5% hispanics and 7.4% blacks compared to 2.4% and 1.6%, respectively, for XM(-) recipients (1-3). Further, more were highly sensitized with 81% having a current PRA greater than 10% and 56% with a peak PRA greater than 80% compared to 65% and 14%, respectively, for XM(-) recipients. More importantly, 19/27 (70%) of the recipient candidates may have had irrelevant positive XMs. The XM(+) patients were classified into five categories defined by: I) autoantibodies; II) transfusions in the 2 weeks prior to the availability of the donor; III) the XM technique; IV) highly sensitized regraft candidates with current and peak PRAs greater than 85% and V) antibody to unreported MHC antigens. Of these, 70% may have been denied a transplant due to IgM autoantibodies or the use of XM techniques lacking extensive evaluation. The authors propose that all XM(+) mandatorily-shared kidneys be examined for IgM autoantibody and that kidneys not be denied to potential recipients due to IgM autoantibody. In addition, to minimize exclusions based on positive B-cell XMs, it is proposed that mandatorily-shared kidneys be shared on the basis of the DR subtypes, insofar as is currently practical. PMID- 1496538 TI - The effects of dietary supplementation with fish oil on renal function and the course of early postoperative rejection episodes in cyclosporine-treated renal transplant recipients. AB - In a randomized prospective coconut oil (daily 6g[63% C8:0 and 36% C10:0] [EPA-] [n = 48])-controlled trial, we investigated the effect of a one-month dietary supplementation with daily 6 g fish oil (30% C20:5 omega-3 and 20% C22:6 omega-3 as their methyl esthers [EPA+] [n = 40]) on the incidence and course of early postoperative rejection in 88 first cadaveric, cyclosporine-treated renal transplant recipients. At one month there were no differences in renal function and incidence of rejection episodes. When analyzed separately for rejection (re+) or nonrejection (re-), the rejecting and fish oil-treated patients showed a significant better recovery of renal function after a histologically confirmed rejection episode, creatinine clearance being 43 ml/min/1.73m2 in the EPA+re+group versus 27 ml/min/1.73 m2 in the EPA-re+group (P less than 0.05), and serum creatinine being 183 and 283 mumol/l (P less than 0.05), respectively. The prerejection renal function and the decline of renal function during the rejection episode did not differ significantly between the EPA+re+ and the EPA re+ groups. The nonrejecting fish oil-treated patients showed no better renal function than the nonrejecting coconut oil-treated patients. However, cyclosporine trough levels were significantly higher in the fish oil-treated group (EPA+re- 251 versus EPA-re- 200 ng/ml [P less than 0.05]). From these results we conclude that dietary supplements with fish oil favorably influence renal function in the recovery phase following a rejection episode in cyclosporine-treated renal transplant recipients. We further conclude that one month after grafting there is no difference in the incidence of rejection episodes between the fish- and coconut oil-treated patients. The same holds true for renal function in the absence of rejection, and for the decline in renal function during a rejection episode. PMID- 1496539 TI - The introduction of microvascular surgery to hepatic artery reconstruction in living-donor liver transplantation--its surgical advantages compared with conventional procedures. AB - Microvascular surgery for the reconstruction of the graft artery has been used since the 8th case in our series of 14 liver transplantations using living related donors, and the clinical results have been compared between the first seven cases (the Loupe group) and the last seven cases (the Micro group). Seven arteries in 7 grafts were reconstructed with the use of loupe magnification in the Loupe group, while 8 arteries in 7 grafts were anastomosed with microscopic techniques in the Micro group. Statistically, there was no difference between the two groups in general background, including age, body weight and primary disease of the recipient, and in medical and surgical factors possibly relating to postoperative thrombosis of the hepatic artery. In two cases in the Loupe group, one or two additional reconstructions were necessary to obtain sufficient blood flow, while 8 arteries were anastomosed in the Micro group without any arterial complication in the postoperative period. There was no difference in time required for completing the arterial reconstruction (45.1 +/- 18.1 min in the Loupe versus 44.4 +/- 6.9 min in the Micro [mean +/- SEM]). Postoperative ultrasonic Doppler duplex study demonstrated a temporary decrease in the arterial flow in 2 cases of the Loupe group, and partial thrombosis of the artery was suspected. Additionally there were two episodes of hepatic artery thrombosis in 1 case of the Loupe group, in which emergent revision for thrombectomy and reanastomosis was performed at the first episode. This illustrated the higher incidence of arterial complications in the Loupe group compared with the Micro group (4 episodes/7 arteries in the Loupe versus 0/8 arteries in the Micro, P less than 0.05). In the present series there were no graft failures or arterial complications in the three deaths in the series. The clinical improvements achieved by microvascular surgery in living-donor liver transplantation suggest an alternative technical strategy for dealing with problematic arterial reconstruction in adult liver transplantation. PMID- 1496540 TI - The association of IgA deficiency but not IgG or IgM deficiency with a reduced patient and graft survival following liver transplantation. AB - Recipients of solid organ allografts require lifelong immunosuppression in order to prevent graft rejection and to maintain graft function. In general, such immunosuppression greatly impairs the cellular immune system, as this level of the immune system is principally responsible for self and non-self recognition. The consequences of allograft transplantation in terms of patient and graft survival when transplants are given to individuals who have a preexisting humoral immune deficiency characterized by a deficiency of the serum levels of one or more of the major Ig classes have not yet been reported. From February 1, 1981 through December 31, 1990, a total of 43 adult patients with a deficiency of 1 or more Ig classes received a ABO-matched liver allograft at this institution. This sample represents 2.5% of a total of 1684 adults transplanted during this interval. These 43 liver graft recipients could be divided into 3 major groups based upon the presence of an IgG, IgM, or IgA deficiency. IgG deficiencies were defined as levels less than 50 mg/dl. Patient and graft survival for the IgA deficient group was significantly reduced (P less than 0.04 and P less than 0.009, respectively) compared with both the IgG- and IgM-deficient groups. The latter two groups did not differ from controls without an Ig deficiency for these same two endpoints. The major causes of death in the IgA-deficient group were sepsis and opportunistic infection. A third of the deaths in the IgA-deficient group occurred in the perioperative period (first 30 days) while greater than 50% of the deaths occurred within the first 3 months, and all deaths occurred before the first year. Based upon these data, the following conclusions can be made: (1) serum IgA deficiency but not IgG or IgM deficiency is associated with an increased post-OLTx death and graft loss rate; (2) the majority of these deaths are due to sepsis or an opportunistic infection; and (3) most of the deaths occur early. These data suggest that recognition of a deficiency of IgA prior to organ grafting necessitates meticulous attention to the prevention of infection in the immediate perioperative period if patient and graft survival of these patients is to be improved. PMID- 1496541 TI - Intragraft immune events after human liver transplantation. Correlation with clinical signs of acute rejection and influence of immunosuppression. AB - Evaluation of graft morphology is regarded as a cornerstone for diagnosis of acute liver graft rejection. Here we have studied the clinical relevance of biopsy findings obtained either by aspiration cytology or by histology in the first month after human liver transplantation, and have assessed the influence of immunosuppressive induction treatment on the incidence of morphological and clinical rejection. Results of 865 aspiration biopsies (TAC) and 155 core biopsies in 141 patients were correlated with the retrospective clinical diagnosis concerning the presence or absence of acute rejection. This analysis demonstrated that there are almost no false negative findings either in cytology or in histology (less than 0.1% of negative biopsies). In contrast, with both methods a large number of positive biopsy results were obtained that were without clinical correlate ("false positive" biopsies; 46% and 41% of positive cytologies and histologies, respectively). The rates of clinical and morphological acute rejections were differently influenced by the type of immunosuppressive induction protocol used. The incidence of clinical rejection was particularly low with a quadruple drug regimen when cyclosporine therapy was started immediately after transplantation (29% vs. 62% when introduction of cyclosporine was delayed for 2 5 days). Morphological rejections were similarly frequent with immediate and delayed introduction of cyclosporine at 2 mg/kg during quadruple therapy (65-75%) and were only reduced with initial high dose cyclosporine treatment (5 mg/kg) (35%). Antirejection treatment was not required in patients with morphological evidence of rejection but without clinical symptoms. The study demonstrates that cytology and histology are similarly reliable for exclusion and similarly unreliable for diagnosis of clinical acute rejection. The clinical relevance of positive biopsy findings is strongly influenced by the basic immunosuppressive treatment. Certain types of induction treatment can obviously alter the alloresponse in a way that no graft damage occurs despite the presence of marked intragraft immune activation. "False-positive" biopsy findings, therefore, seem to represent a qualitatively modified and self-limited type of intragraft alloresponse that is without clinical consequences ("incomplete" or "subclinical" rejection). PMID- 1496542 TI - Binding of phycoerythrin-conjugated interleukin-6 to in vitro-activated human peripheral blood mononuclear cells--effect of immunosuppressive agents and of a calcium channel blocker. AB - We studied the effect of cyclosporine A, prednisolone, and the Ca2+ channel blocker verapamil on interleukin-6 binding to mitogen-activated peripheral blood mononuclear cells, using a flow cytometric technique and phycoerythrin-conjugated IL-6. All mitogenic stimuli up-regulated IL-6 binding to a variable degree. PHA alone or in combination with PMA was the most effective stimulant in up regulating IL-6 binding in all the experiments performed. The main changes in IL 6 binding were seen in the large cell cluster, which consisted mainly of lymphoblasts. PHA and PHA/PMA, however, also up-regulated the mean fluorescence intensity on the small cell cluster, which consisted mainly of quiescent lymphocytes. The overall effect of the three pharmacological agents on mitogen-up regulated IL-6 binding was minimal; most significant were a down-regulation by all three agents of IL-6 binding by small lymphocytes in PHA/PMA cultures, a down regulation of IL-6 binding by CsA in PHA/PMA-induced large PBMC, and an up regulation by verapamil of PMA-induced IL-6 binding in large PBMC. Measurements of IL-2 binding and of IL-6 production in the same cultures showed a different pattern than that seen with IL-6 binding, as well as different CsA, prednisolone, and verapamil action. In conclusion, by using a new flow cytometric technique providing information both about the quantity of bound cytokine and about the proportion of IL-6-binding cells, we have demonstrated that IL-6 receptor expression in vitro by PBMC can be up-regulated by the use of stimulants differing in the signal transduction pathways they activate. In addition, by using different pharmacological agents and stimuli to dissect different activation pathways of the in vitro immune response, we conclude that IL-6R generation is regulated differently from IL-6 production. Furthermore, since CsA and prednisolone are known inhibitors of in vitro IL-2 production, our results indicate that IL-6R generation does not rely exclusively on the presence of IL-2. PMID- 1496543 TI - The role of fibroblasts in dermal vascularization and remodeling of reconstructed human skin after transplantation onto the nude mouse. AB - The vascularization and the dermal remodeling of two different types of human skin reconstructed "in vitro" and grafted onto the nude mouse were studied. They were composed of human keratinocytes grown either on a human acellular deepidermized dermis (DED), or on a lattice composed of human fibroblasts embedded in bovine type I collagen, a living dermal equivalent (LDE). At different stages after grafting, the transplants were harvested and processed for an immunohistological study with species-specific and non-species-specific antibodies. At one month after grafting, the two types of grafted dermis contained blood vessels whose vascular basement membranes were labeled with a mouse-specific anti-type IV collagen antibody. With an antibody specific for human type IV collagen, a constant labeling of the vascular basement membrane was only observed in the LDE containing fibroblasts. In the DED, a constant association of the mouse endothelial cells with human type IV collagen was observed at early stages after grafting. At later stages, the human type IV collagen progressively disappeared. On the other hand, the dermal-epidermal junction underneath the human epidermis contained human type IV collagen in the two types of reconstructed skin. Labeling with the species-specific antibodies directed against human or murine type I collagen showed that the ratio murine type I collagen versus human type I collagen increased with time, suggesting that the DED is progressively invaded by mouse fibroblasts that produce the mouse collagen. On the other hand, in the LDE, the preexisting bovine type I collagen became progressively undetectable while both human type I collagen and elastic fibers were deposited by numerous human fibroblasts. Mouse type I collagen was not detected. Altogether, these observations made by grafting human skin reconstructed "in vitro" onto the nude mouse should be interesting for evaluating the usefulness of grafting a dermal substrate together with the epidermal sheet in the treatment of burns. PMID- 1496545 TI - Increased islet allograft survival after extended culture by a mechanism other than depletion of donor APCs. Lack of correlation between the elimination of donor MHC class II-positive accessory cells and increased transplantability. AB - Neonatal rat islets derived by nonenzymic (in vitro) isolation procedures from the Fischer-344 (F-344, Rt1lv1) strain have been shown to be freely transplantable across complete MHC barriers without the use of any form of immunosuppression. However, islets obtained by in vitro isolation from some donor strains, such as the ACI, retain a degree of immunogenicity upon transplantation. This study examined the immunogenic nature of these neonatal ACI islets, and correlated this with the presence of a residual population of MHC class II positive antigen presenting cells within the islets. In addition, further reduction of immunogenicity of isolated neonatal ACI islets by extension of the culture period was examined. Islets were obtained from neonatal ACI donors by culture-isolation and placed in secondary culture for either 2 days (10 day total culture period, standard culture) or 42 days (50 day total culture period, extended culture). Standard-culture ACI islets were rejected 33% to 100% of the time in five different recipient strains (depending on recipient strain). Compared with control grafts of fresh pancreatic fragments, rejection rates were significantly lower in two strain combinations (ACI to BUF, P = 0.044 and ACI to F-344, P = 0.028), and for all recipient strains combined (P less than 0.001). Extended-culture ACI islets survived significantly longer in all five recipient strains tested (ACI to BN, P = 0.024; ACI to BUF, P = 0.005; ACI to LEW, P = 0.004; ACI to F-344, P = 0.008 and ACI to WF, P = 0.024) and for all strains combined (P less than 0.001). No MHC class II-positive cells were detected upon examination of sectioned neonatal ACI islets using peroxidase immunocytochemistry (OX-6 antigen) in either the standard-culture or extended-culture groups. These results suggest that the increased survival of grafts of extended culture ACI islets is due to a mechanism other than the elimination of class II-positive APCs from the islets. Although possible down-regulation of MHC class II expression on residual APCs during the culture process may make identification of these cells difficult, alternative mechanisms such as the down-regulation of MHC class I antigen, resulting in the reduction of available donor target, or the existence of an accessory cell that is not constitutively MHC class II-positive, may be responsible for this increased graft survival. PMID- 1496544 TI - Cytokine gene expression in rejecting cardiac allografts. AB - Heart transplantation is now a viable therapeutic option for patients with certain end-stage cardiac diseases. However, episodes of rejection, opportunistic infection, and life-threatening side effects of generalized immunosuppression remain very real problems for these patients. A better understanding of the molecular mechanisms underlying rejection may provide the basis for the development of more specific, less toxic immunosuppressive therapies. While cytokines have long been implicated in the pathogenesis of rejection, the precise role of each cytokine in this process has yet to be defined. We report here the application of the polymerase chain reaction (PCR) to the detection of cytokine mRNA in biopsies obtained from heterotopic abdominal cardiac allografts in cynomolgus monkeys. With the exception of IL-6 and IL-8, cytokine transcripts were undetectable in samples obtained from the donor heart pretransplant. In contrast, IFN-gamma transcripts were detected in all transplants two days after surgery before evidence of rejection was demonstrable by histopathologic analysis. IL-1 beta, IL-2, and IL-6 transcripts were detected when minimal rejection was noted. At later times, IL-1 alpha, IL-1 beta, IL-2, IL-6, IL-8, TNF beta, and IFN-gamma transcripts were detectable. Further characterization of the spectrum of cytokines expressed at various stages of rejection may lead to insights into the biology of transplant rejection and to the development of more specific and potent reagents to diagnose and/or treat rejection. PMID- 1496546 TI - B-B10 (anti-CD25)-saporin immunotoxin--a possible tool in graft-versus-host disease treatment. AB - An immunotoxin containing the B-B10 MoAb, directed against the CD25 determinant, and the ribosome-inactivating protein saporin, inhibits 3H-TdR incorporation in phytohemagglutin, allogeneic-stimulated lymphocytes (primary and secondary mixed lymphocyte reaction), and in an alloreactive T cell clone. A lower degree of inhibition was obtained with the B-B10 MoAb, which is known to inhibit IL-2 activity, as well as with the unconjugated compounds. These results suggest that the in vivo administration of the conjugate might be a more effective tool in the treatment of patients affected by graft-versus-host disease than B-B10 alone, by inducing an efficient killing of allogeneic-reacting T lymphocytes. PMID- 1496548 TI - Are calcium channel blockers protective against first-dose reactions to OKT3? PMID- 1496550 TI - A technique for successful transplantation of organs from non-heartbeating cadaver donors. PMID- 1496549 TI - Liver transplantation for cirrhosis following jejuno-ileal bypass--regional cytokine differences associated with pathological changes in the transplant liver. PMID- 1496547 TI - Transplantation effects of a unique major histocompatibility complex class I mutation. AB - This study describes a novel MHC class I mouse mutant that was discovered because of loss of reactivity of its cells to monoclonal antibodies. The mutation occurred in the H-2Ks molecule and is the first in vivo mutation described that has a single altered amino acid residue (amino acid 107) distant from the regions considered to be peptide or TCR contacts. Nevertheless, skin grafts from the mutant to the parent are rejected by CD8+ T-cells. In the reciprocal direction, the mutant shows partial tolerance to parental skin grafts, suggesting that the mutant is inefficient in selecting alloreactive T-cells specific for the wild type Ks molecule. PMID- 1496551 TI - Long-term small-bowel graft survival induced by a spontaneously tolerated liver allograft in inbred rat strains. PMID- 1496552 TI - Modification of rat skin allograft rejection by inhibition of thromboxane synthesis. PMID- 1496553 TI - Telomere positional effects and the regulation of cellular senescence. AB - Normal cells have a limited capacity to proliferate but the molecular clock that regulates the onset of cellular senescence remains unidentified. The ends of chromosomes--telomeres--have been shown to shorten progressively with age in normal cells. Here, we present a working model of how telomeric shortening may induce programmed changes in the regulation of cellular proliferation. PMID- 1496554 TI - Genetic testing in the workplace: a view from the USA. AB - Progress in human genetics, accelerated by the Human Genome Project, is leading to a rapid proliferation in the number of genetic tests. Although they have their benefits, genetic tests have in the past been used by various societal institutions, including employers, to discriminate against and stigmatize individuals. In the light of the increase in the number of tests and some current reports of discrimination in employment, a variety of legal and regulatory measures have been proposed to prevent genetic discrimination in the workplace. PMID- 1496555 TI - Patterning of the Drosophila nervous system: the achaete-scute gene complex. AB - The genes of the achaete-scute complex (AS-C) confer on cells the ability to become neural precursors. Their expression is restricted to groups of cells, the proneural clusters, which occupy specific positions within the embryo neural anlagen and the larva imaginal discs. Neuroblasts or sensory organ mother cells are born within these clusters. Thus, the patterns of expression of the AS-C genes help to define the topology of the nervous system. PMID- 1496556 TI - Developmental choices in mating-type interconversion in fission yeast. AB - Fission yeast cells follow a specific pattern of mating (cell) type switching in single cell pedigrees. Asymmetric cell divisions producing sisters of different developmental fates result from inheritance of specific parental DNA strands according to the classical model of semiconservative replication and segregation. PMID- 1496557 TI - Models of plant-pathogen coevolution. AB - Plant populations are often genetically polymorphic for resistance to pathogens. The effectiveness of this resistance is limited because the pathogens are, in turn, polymorphic for virulence genes that can evade plant resistance. Theoretical models and intriguing preliminary data suggest that these plant pathogen polymorphisms are maintained by continual cycles of coevolution within populations, combined with occasional immigration of new virulence and resistance genes from distant populations. PMID- 1496558 TI - Immunosuppression for organ grafting. PMID- 1496560 TI - Tissue typing and organ transplantation: proposal for establishment of an HLA network system for bone marrow transplantation in Asia. PMID- 1496559 TI - Prospects for synergistic immunosuppressive drug therapy in the coming decade. AB - The major clinical strategy during the past three decades has been to discover a single drug that achieves immunosuppression with minimal toxic side effects. Regimens to optimize CyA immunosuppressive therapy have been limited by marked interindividual variations in drug pharmacokinetics and pharmacodynamics that cause simple drug administration routines to produce variable clinical outcomes. The approach presented herein seeks to employ multiple immunosuppressive agents that act synergistically to inhibit alloactivation. Using the rigorous median effect analysis, synergistic interactions have been discerned both using in vitro systems, as well as in vivo transplant situations. CyA has a profoundly synergistic interaction with RAPA, and a moderately synergistic effect with QCA. The next decade presents important opportunities to determine whether these immunologic effects are beclouded by synergistic drug toxicities. Studies of this type may allow us to achieve a uniformly effective, yet well-tolerated, immunosuppressive regimens in the future. PMID- 1496561 TI - Some problems with organ preservation. PMID- 1496562 TI - Development of malignancy following renal transplantation in Australia and New Zealand. PMID- 1496564 TI - Heart transplantation in Thailand. PMID- 1496563 TI - Early pitfalls in renal transplantation. PMID- 1496566 TI - Pancreas transplantation--1991. PMID- 1496565 TI - Developments in segmental and living related liver transplantation. PMID- 1496567 TI - Diversity in mRNA encoding soluble form MHC class I-like molecules in human tissues. PMID- 1496568 TI - The establishment of two monoclonal antibodies that recognize canine MHC class II antigens. PMID- 1496569 TI - Beneficial effect of sharing six-antigen-matched cadaver kidneys in the United States. PMID- 1496570 TI - Is HLA-DRw6 antigen matching necessary in living donor renal transplant? PMID- 1496571 TI - Clinical experience in Rh-incompatible kidney transplantation. PMID- 1496572 TI - Living unrelated donor renal transplantation. PMID- 1496573 TI - Profile of an Asian "opting-out" system--the institutional and legal arrangements in Singapore. PMID- 1496574 TI - Use of elderly living related donors in renal transplantation. PMID- 1496575 TI - Development of a reliable method for procurement of warm ischemic kidneys from non-heart-beating donors. PMID- 1496576 TI - A new method to harvest multiple organs from non-heart-beating donors by use of a percutaneous cardiopulmonary support machine. PMID- 1496577 TI - Salvage of warm ischemic pancreas from non-heart-beating donors by a core-cooling method with cardiopulmonary bypass. PMID- 1496578 TI - Anatomical study of the left renal vein and its draining veins, as encountered during living donor nephrectomy. PMID- 1496579 TI - The gift of life from prisoners sentenced to death: preliminary report. PMID- 1496580 TI - Opting-out law: a model for Asia--the Singapore experience. PMID- 1496581 TI - A new splitting technique for simultaneous transplantation of liver, pancreas, duodenum, and spleen in pigs. PMID- 1496582 TI - Renal transplantation using ileal conduit. PMID- 1496583 TI - Experimental tooth germ transplantation--study on circulatory recovery in the grafts. PMID- 1496584 TI - Effects of prostaglandin E1 on transplanted kidneys in dogs by laser Doppler blood perfusion monitor. PMID- 1496585 TI - Preservation of cadaveric kidney allografts. PMID- 1496586 TI - Protective effect of superoxide dismutase and allopurinol on oxygen free radical induced damage to the kidney. PMID- 1496587 TI - Effects of prostaglandin E1 on rat cardiac allografts with cyclosporine. PMID- 1496588 TI - The effect of cyclosporine on warm ischemic kidneys in rats. PMID- 1496589 TI - The effect of lipo-prostaglandin E1 on canine femoral arterial allografts. PMID- 1496590 TI - Immunosuppressive effect of bactobolamine. PMID- 1496591 TI - Pulse therapy for rejection with deoxyspergualin in renal recipients: a multicenter controlled study. PMID- 1496592 TI - Experience gained from the administration of 15-deoxyspergualin for recurrent graft rejection in kidney transplant recipients. PMID- 1496593 TI - Improvement of renal function in transplanted kidneys with a new immunosuppressive drug, 15-deoxyspergualin: treatment of chronic rejection. PMID- 1496594 TI - Studies of immunosuppression with quadruple regimen treatment (cyclosporine, mizoribine, prednisolone, and antilymphocyte globulin) in cadaveric and living related donor renal allotransplantation. PMID- 1496595 TI - Correlation of cyclosporine-induced nephropathy with renal microsomal cytochrome P-450: the preventive effect of verapamil. PMID- 1496596 TI - Differential diagnosis of kidney transplant rejection and cyclosporine nephrotoxicity by urine cytology. PMID- 1496597 TI - Cyclosporine-induced hyperuricemia after renal transplant: clinical characteristics and mechanisms. PMID- 1496598 TI - Cyclosporine-induced gingival overgrowth. PMID- 1496599 TI - Site-specific immunosuppression for corneal graft survival in the rat. PMID- 1496600 TI - Prolongation of rat renal allograft survival by the synergistic effects of azathioprine and cholera toxin. PMID- 1496601 TI - A gamma-lactone immunosuppressant inhibits the generation of macrophage killer cells and prolongs skin allograft survival in the rat. PMID- 1496602 TI - A new fluorochromasia assay for sensitivity of lymphocytes to immunosuppressants. PMID- 1496603 TI - Delay of acute rejection of canine pancreatic allograft by ex vivo perfusion with anti-class II monoclonal antibody. PMID- 1496604 TI - Five-year results of thoracic duct drainage in living related donor kidney transplantation. PMID- 1496605 TI - Cadaveric kidney transplantation from donors with prolonged warm ischemia time. PMID- 1496606 TI - Superior renal allograft survival among Asian recipients. PMID- 1496607 TI - Graft survivals greater than 15 years in renal transplant recipients. PMID- 1496608 TI - Quality of life of ESRD patients: development of a tool and comparison between transplant and dialysis patients. PMID- 1496609 TI - Impact of early graft function on the long-term outcome of living donor kidney transplants. PMID- 1496610 TI - Long-term follow-up of living related donors at a single center in Taiwan. PMID- 1496611 TI - Analysis of prognostic factors affecting renal allograft survival. PMID- 1496612 TI - Single-center experience of 600 living donor renal transplants: univariate analysis of risk factors influencing allograft outcome. PMID- 1496613 TI - Immunology of renal transplantation in Singapore: the cyclosporine era. PMID- 1496614 TI - Two hundred and thirty cases of kidney transplantation: single-center experience in Taiwan. PMID- 1496615 TI - Outcome of kidney transplantation from non-heart-beating donors: comparison with heart-beating donors. PMID- 1496616 TI - A living-related donor kidney transplant functioning for 20 years: a case report. PMID- 1496617 TI - Surgical complications in kidney transplantation: experience in 100 kidney transplants at Ramathibodi Hospital. PMID- 1496618 TI - Staged vascular access for hemodialysis in end-stage renal disease patients. PMID- 1496619 TI - Interleukin-6 in bile as a marker of allograft rejection following liver transplantation in man. PMID- 1496620 TI - Significance of a positive crossmatch on outcome in human liver transplantation. PMID- 1496621 TI - Abatement of secondary amenorrhea in Wilson's disease following liver transplantation. PMID- 1496622 TI - Partial liver transplantation from living related donors. AB - Living related liver transplantation was performed in five cases between June 1989 and July 1991 at Shinshu University Hospital. All of the donors were fathers of the patients and blood type was identical in each case. All of them were discharged from the hospital 2 weeks after hepatectomy without any complications. They started to work 2 months after surgery. Four recipients are surviving but one died. Three are enjoying daily life 17 months after LT in case 1, 5 months after LT in case 4, and 4 months after LT in case 5. Case 2 is still in the hospital 14 months after LT. Advantages of LRLT we noted were (1) cases can be performed totally electively and allow full preparation for the family and the transplant team, (2) primary graft nonfunction has not been observed to date, and (3) 38 patients received the chance of liver transplantation in their own country, which under current legislation would not otherwise have been possible. Disadvantages of LRLT were (1) partial hepatectomy was performed in healthy persons, and (2) retransplantation is difficult. PMID- 1496623 TI - Experience in anesthesia for liver transplantation. PMID- 1496624 TI - Fulminant hepatic failure and liver transplantation. PMID- 1496625 TI - Acquired hemolytic anemia after ABO-unmatched liver transplantation. PMID- 1496626 TI - Liver transplantation: the Chang Gung experience. PMID- 1496627 TI - Biliary complications following orthotopic liver transplantation. PMID- 1496628 TI - Disappearance of Kayser-Fleischer rings following liver transplantation. AB - 1. Four cases of Kayser-Fleischer rings of Wilson's disease were observed to disappear after liver transplantation. 2. The disappearance of Kayser-Fleischer rings was in reverse order from that in which they appear. 3. The duration of disappearance was variable. 4. The density of Kayser-Fleischer rings correlated with the duration of clinical symptoms. PMID- 1496629 TI - Respiratory changes and pulmonary complications following orthotopic liver transplantation. AB - In conclusion, we observed a worsening of LIS post-OLT, especially on the fourth postoperative day. The drop in this score implies a complicated course accompanied by a high mortality rate and increased medical expenses. Among the four components, oxygenation index and chest roentgenography score play an important and practical role. Measuring the AaD(O2) has its clinical merit, while the PEEP score and compliance of the respiratory system are of limited usefulness in this setting. The pleural effusions developed after OLT showed a trend towards increasing in amount until the sixth day and then gradually decreasing, except those cases with complications. PMID- 1496630 TI - Effects of terminal cardioplegia with leukocyte-depleted blood on myocardial adenosine triphosphate in heart grafts preserved for 24 hours. PMID- 1496631 TI - Impaired mechanical efficiency after 24-hour preservation of canine hearts. PMID- 1496632 TI - Rejection prophylaxis with antilymphocyte globulin for cardiac transplantation in Oriental recipients. PMID- 1496634 TI - The role of natural killer cells in heart-lung transplanted mice. PMID- 1496633 TI - Usefulness of cytokines in early detection of canine lung allograft rejection. PMID- 1496635 TI - Changes of mucosal immunologic function in graft-vs-host reaction after small bowel transplantation. PMID- 1496636 TI - Comparative evaluation of systemic vs portal venous drainage in long-term surviving rats with orthotopic small bowel transplantation. PMID- 1496637 TI - Inhibition of natural killer (NK) cell prevents graft-vs-host-disease after small bowel transplantation in rats. PMID- 1496638 TI - A simple technique for small bowel transplantation in rodents. PMID- 1496639 TI - Transplantation of purified cryopreserved canine islet allograft. PMID- 1496640 TI - Optimizing cooling rates for cryopreservation of isolated pancreatic islets. PMID- 1496641 TI - Marked prolongation of islet xenograft survival (hamster to mouse) by microencapsulation and administration of 15-deoxyspergualin. PMID- 1496642 TI - The development of fetal porcine islet cells as xenografts: preliminary observations. PMID- 1496643 TI - Long-term survival and proliferation of spheroidal aggregate cultured hepatocytes transplanted into the rat spleen. PMID- 1496644 TI - Successful reinduction of remission with low-dose Ara-C in a patient with myelodysplastic syndrome relapsed after allogeneic bone marrow transplantation: restoration of donor hematopoiesis detected by amplification of minisatellite genes. PMID- 1496645 TI - Bone marrow transplantation for malignant histiocytosis. PMID- 1496646 TI - Allogeneic bone marrow transplantation in the treatment of leukemia: emphasis on graft-vs-host disease and veno-occlusive disease in a Taiwan Chinese series. PMID- 1496648 TI - Autologous bone marrow transplantation for plasma cell leukemia: report of a case. PMID- 1496647 TI - Toxicity of high-dose busulfan and cyclophosphamide as a preparative regimen for bone marrow transplantation. PMID- 1496649 TI - High-dose chemotherapy with support by autologous bone marrow and GM-CSF in the treatment of advanced ovarian cancer: preliminary report of a new strategy. PMID- 1496650 TI - A case report of living-related kidney transplantation between hepatitis B antigen carriers. PMID- 1496651 TI - Renal transplantation is not contraindicated in hepatitis B surface antigen positive patients. PMID- 1496652 TI - Analysis of urine cytology by flow cytometry in renal transplantation. PMID- 1496653 TI - Urinary active T-rosette-forming cells in the diagnosis of acute allograft rejection after cadaveric kidney transplantation. PMID- 1496654 TI - Urinary tissue type plasminogen activator and plasminogen activator inhibitor in renal transplant patients. PMID- 1496655 TI - Fine needle aspiration biopsy of human renal transplants. PMID- 1496656 TI - A Candida antigen detection system for fungus infection in renal transplant patients. PMID- 1496657 TI - Improved survival of renal allograft recipients with Pneumocystis carinii pneumonia by early diagnosis and treatment. PMID- 1496658 TI - Clinical study of infectious disease in renal transplant recipients. PMID- 1496659 TI - Effects of sex steroid hormones, estradiol and testosterone on the survival time of skin allografts in rats treated with total body irradiation. PMID- 1496660 TI - Kidney transplantation in diabetic patients. PMID- 1496661 TI - Usefulness of protein-restricted diet and recombinant human erythropoietin in patients with chronic rejection of a transplanted kidney. PMID- 1496662 TI - Female gonadal function after renal transplantation. PMID- 1496663 TI - Clinical and experimental studies of acute pancreatitis after renal transplantation. PMID- 1496664 TI - Clinical characteristics and possible risk factors in postrenal transplant diabetes mellitus. PMID- 1496665 TI - Hypertension following successful renal transplantation. PMID- 1496666 TI - Lipid disorders in renal transplant recipients. PMID- 1496668 TI - Lymphoma in cyclosporine-treated renal transplant recipients. PMID- 1496667 TI - A statistical study of cancer incidence in renal transplant patients. PMID- 1496669 TI - Protective effects of a PAF antagonist against liver injury induced by warm ischemia or cold preservation. PMID- 1496670 TI - Twenty-four-hour preservation of beagle livers with University of Wisconsin solution. PMID- 1496671 TI - Experimental orthotopic liver transplantation using TOM-2H solution, in which the major anion is gluconate: a preliminary report. PMID- 1496672 TI - Transplantation unresponsiveness induced by liver allografts in mouse strains with various histocompatibility disparities. PMID- 1496673 TI - An analysis of the xenogeneic response in an isolated liver perfusion circuit. PMID- 1496674 TI - Living donor segmental liver transplantation in dogs. PMID- 1496675 TI - Usefulness of monitoring the ICG retention rate as an early indicator of allograft function in liver transplantation. PMID- 1496676 TI - Ischemic liver injury induced by calcium released from mitochondria. PMID- 1496677 TI - Changes of thromboxane B2 level in experimental orthotopic liver transplantation in swines--the effect of warm ischemia and thromboxane A2 synthetase inhibition. PMID- 1496678 TI - Hepatic protein synthesis rate of biopsied liver tissue in the assessment of preservation solutions. PMID- 1496679 TI - Effect of short-term administration of deoxyspergualin in rat allogeneic renal transplantation. PMID- 1496680 TI - Influence of cyclosporine on glucose tolerance in rats. PMID- 1496681 TI - Prolonged survival of cardiac allografts and xenografts in rat-to-rat and hamster to-rat transplantation by treatment with deoxyspergualin. PMID- 1496682 TI - Downregulation of the immune system: where can we interfere? PMID- 1496683 TI - Selective suppression of T-cell activation by administration of MHC class II binding peptides. PMID- 1496684 TI - The continuing search for new immunomodulators. PMID- 1496685 TI - Toxicologic evaluation of the new cyclosporin derivative, SDZ IMM 125, in a comparative, subchronic toxicity study in rats. PMID- 1496686 TI - Molecular mechanism of immunosuppressive agents. PMID- 1496687 TI - Cyclosporine and its analogue SDZ IMM 125 mediate very similar effects on T-cell activation--a comparative analysis in vitro. PMID- 1496688 TI - Xenotransplantation: a view of issues. PMID- 1496689 TI - Clinical experience with sandimmune (cyclosporine) in autoimmune diseases. PMID- 1496690 TI - Cyclosporins past, present, and future. PMID- 1496691 TI - Clinical development of cyclosporine. PMID- 1496692 TI - Selectivity still has its price: personal experiences with cyclosporine over the last 10 years. PMID- 1496693 TI - Kidney transplantation in the cyclosporine era--the Munich experience. PMID- 1496694 TI - Immunophilin structure: a template for immunosuppressive drug design? PMID- 1496695 TI - Cyclosporine in heart transplantation. PMID- 1496696 TI - Past, present and future in liver transplantation immunosuppression. PMID- 1496697 TI - Cyclosporine in bone marrow transplantation. PMID- 1496698 TI - Factors leading to improved outcome following pancreas transplantation--the influence of immunosuppression and HLA matching. AB - The results of pancreas transplantation continue to improve and do not appear to have plateaued worldwide. In the United States, pancreas graft survival rates are now similar or better than those for other organ transplants, particularly when the pancreas is transplanted simultaneously with a kidney. Since 1987, more than three fourths of uremic recipients of simultaneous pancreas and kidney grafts are insulin independent and dialysis-free more than 1 year after transplantation. Although there is room for improvement in the results of solitary pancreas transplants, more than half of these patients are insulin independent at 1 year. A successful pancreas transplant results in near normalization of glucose metabolism and lowers glycosylated hemoglobin to normal levels. While a successful pancreas transplant may not elevate all diabetic patients to the level of health and function of the general population, pancreas transplant recipients report a significantly better quality of life than do those patients who remain diabetic. As the success rate of pancreas transplantation continues to improve, this treatment should be considered as a means for restoring a normal glucose level in type I diabetic patients before the development of advanced, disabling complications of the disease. Our recommendation for an approach to minimizing the antirejection response and maximizing graft survival rates in pancreas transplant recipients is to use quadruple immunosuppressive therapy with the induction doses higher than those employed for other organ transplant recipients. For SPK recipients, the allocation of organs should follow the scheme used for that of a kidney alone.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1496699 TI - Parasitological, clinical and haematological response of children with Plasmodium falciparum to 4-aminoquinolines and to pyrimethamine-sulfadoxine with quinine in western Kenya. AB - Children with Plasmodium falciparum infections in Western Province, Kenya, were studied in 1987 for their parasitological, clinical and haematological response to chloroquine, to amodiaquine and to pyrimethamine-sulfadoxine plus quinine. Ninety-eight children under 5 years of age were treated in 1 of 2 hospitals. Of the 56 patients treated with chloroquine base 25 mg/kg, 91% had resistant infections, with 36% having no significant decrease in parasitaemia (RIII resistance); however, 69% responded clinically within a week. Of the 27 patients treated with amodiaquine base 25 mg/kg, 67% had resistant infections, with 7% RIII resistant; 81% responded clinically. The parasites cleared in all 15 children given pyrimethamine-sulfadoxine plus 3 days of quinine. Only when parasites cleared did patients have improved haemoglobins and haematocrits. This study shows that parasitaemia in children hospitalized in western Kenya responds poorly to 4-aminoquinolines, although the patients improve clinically, at least during the first 7 days. Young children may need to clear parasites to avoid the risk of severe anemia and the need for blood transfusions. PMID- 1496700 TI - Three cases of human Sarcocystis infection with a review of human muscular sarcocystosis in Malaysia. AB - Three cases of muscular sarcocystosis from West Malaysia are reported. The morphological features of the parasites from these three cases are similar to the eight cases previously reported from this country. A review of this total of eleven cases of muscular sarcocystosis showed that they were all incidental findings, where man acted as intermediate hosts of as yet unknown Sarcocystis spp. These cases of muscular sarcocystosis were probably zoonotic in origin and associated with close contact with definitive hosts (both domestic and wild animals) thus permitting the contamination of food and drink with sporocysts shed by these definitive hosts. These infections were probably acquired locally as most of the subjects were born in Malaysia and none had ever left the country to stay elsewhere. Eight of the eleven cases reported were associated with malignancies, especially of the tongue and nasopharynx. PMID- 1496701 TI - Visceral larva migrans in seven members of one family in Trinidad. AB - The occurrence of the first seven cases of visceral larva migrans in Trinidad and Tobago is described. All cases occurred in children of the same family. The ELISA test was used to confirm the clinical diagnosis. PMID- 1496702 TI - Result of treatment in children with tuberculosis. Evaluation of indications for and results of treatment in a 5 years cohort of children treated for tuberculosis in Turiani Hospital Tanzania. AB - Between January 1983 and January 1988 a total of 146 children started tuberculosis (TB) treatment in Turiani Hospital, Tanzania. During the treatment period 16 children died and another 16 were transferred out. From the remaining 114 children, 84 could be traced and were visited at home. Out of this group 85% were found to be in good clinical condition, whereas 7% had a moderate condition and 1% were seriously ill. Tuberculin sensitivity testing has been carried out in 53 children from the follow-up group. The indications for treatment and the results of the follow-up study are discussed. PMID- 1496703 TI - Prevalence of hepatitis B surface antigen (HBsAg) in blood donors from Bombay. AB - Analysis of serum samples from 3104 blood donors from Bombay screened for hepatitis B surface antigen (HBsAg) by ELISA. HBsAg was detected in 4.7% of the subjects. Relatives showed a significantly higher prevalence of HBsAg than volunteer donors. There was no significant association between HBsAg positivity and a particular blood group. PMID- 1496704 TI - Glycosylated haemoglobin HbA1c and HbS1c in non-diabetic Nigerians. AB - Normal glycosylated haemoglobin levels were determined by the Bio-Rad Haemoglobin A1c by Column Assay, in a large series of non-diabetic Nigerians. Subjects having normal haemoglobin genotype (HbAA) and the common haemoglobinopathies, namely heterozygous sickle cell trait (HbAS) and homozygous sickle-cell anaemia (HbSS) were studied. The group mean uncorrected %HbS1c levels in the HbSS subjects were significantly higher than %HbA1c levels in the HbAA (p less than 0.02) and HbAS (p less than 0.001). However, after correction for HbS and HbF the sickle-cell trait group had a %HbA1c value significantly higher than the %HbS1c value in the HbSS subjects (p less than 0.001). Since the haemoglobinopathies influence the glycosylated haemoglobin results, hence its interpretation, the need to correct observed results for the presence of abnormal haemoglobin has been emphasised. Only then would the application of a glycosylated haemoglobin test be truely meaningful in the management of diabetic patients with the 'S' haemoglobin. PMID- 1496705 TI - Obstructed duodenal ulcer syndrome. Observations from Kano, Northern Nigeria. AB - 23 patients with obstructed duodenal ulcer syndrome presented in a government hospital in Kano, Northern Nigeria within a 14 months period. One presented in acute obstruction while the remaining twenty two were chronic cases. Only one patient sought medical attention before the onset of symptoms of obstruction. These figures suggest that obstructed duodenal ulcer syndrome is fairly common in Kano and that most patients with uncomplicated duodenal ulcer there do not seek proper medical attention. Duodenal ulcer is therefore probably not as uncommon there as current literature suggests. PMID- 1496706 TI - Causes of blindness in children in the blind schools of Ethiopia. AB - A total of 721 children in the six schools for the blind in Ethiopia were studied. In 1988-1989 histories were taken to ascertain the predisposing factors and ophthalmological examinations and records were used to determine the causes of blindness. Ninety-five per cent of those examined had bilateral blindness, 12% did not know how they had become blind and, of those who provided information on how they became blind, 21% knew that they were born blind, 30% implicated measles as being responsible, and 13% implicated 'mitch' which is an Amharic term used to describe a very wide range of nonspecific and vague illnesses of which measles probably constitutes a significant proportion. Seventy per cent of the blindness was due to either corneal opacity or phthisis bulbi. Of those with non-congenital bilateral corneal opacity or phthisis bulbi, 40% were preceded by measles and 17% by mitch. A study of 66 adults in the handicraft and skill-training centres attached to the blind schools indicated that the principal predisposing factors of blindness were mitch (30%), smallpox (15%), cataract (12%), and traditional eye medicine (11%). Seventy percent had corneal scars of phthisis bulbi and 14% cataract. PMID- 1496707 TI - A new EPI strategy to reach high risk urban children in Bangladesh: urban volunteers. AB - Many community based outreach programs in low income countries utilize illiterate women to provide health services. However, illiteracy may present special problems in immunization or other programs requiring extensive record-keeping and follow-up. In a trial involving twenty-nine volunteers from urban slum communities in Dhaka, Bangladesh, a community-based referral and record-keeping system for use by semi-literate and illiterate volunteers in immunization outreach activities was evaluated over a thirteen month period. The women were uniformly, regardless of literacy, able to use the system to effectively refer and follow-up clients. Although volunteer performance as measured by numbers of referrals was below initial targets, completion rates were high; 87% of children and 96% of women referred completed the full series of immunizations. By facilitating active community participation, the system provides a feasible approach to reducing the high drop-out rates currently associated with immunization programs. PMID- 1496708 TI - Young coconut water for home rehydration in children with mild gastroenteritis. AB - Coconut water was evaluated as a home glucose electrolyte solution for well nourished children with mild diarrhoea. We describe the chemical composition of coconut water by type and age of coconut (Cocos nucifera). Our results suggest that young coconut water can be used, together with early refeeding, as a home glucose electrolyte oral rehydration solution in the early stages of mild diarrhoeal disease, despite not having a balanced electrolyte composition. However, it should not be used in patients with severe cholera, or in patients who are dehydrated and/or in whom renal function is impaired. PMID- 1496709 TI - The sixth case of lagochilascariasis minor in Surinam. AB - The sixth case of lagochilascariasis minor in Surinam is reported in a 13-year old boy. He had abscesses on the right and left side of the neck, with fistulae out of which eggs, larvae and adult worms were expelled. Treatment with thiabendazole and levamisole were ineffective. Finally he was cured after prolonged treatment with albendazole. This is probably the 63rd case of lagochilascariasis minor in the world, but there is a possibility that infection with this rare nematode is underreported. PMID- 1496710 TI - Fatal lipoid pneumonia in an infant complicated by Mycobacterium fortuitum infection. AB - We report a fatal case of lipoid pneumonia in a two and one half month old Saudi female caused by aspiration of animal fat, ghee and complicated by Mycobacterium fortuitum infection. It highlights the need to look for M. fortuitum in lipoid pneumonia and suggests the prevention of the condition through health education. PMID- 1496711 TI - Combined intrauterine and extrauterine gestation with a general surgical presentation. AB - A case is presented of a combined intrauterine and extrauterine gestation. The diagnosis of the ectopic pregnancy was made intraoperatively with a pre-operative diagnosis of a simple intestinal obstruction, while the intrauterine pregnancy was diagnosed after a spontaneous abortion. A family history of twinning associated with a surgical evidence of chronic inflammatory disease is thought to be the cause. PMID- 1496712 TI - Hysterical paralysis as a complication of snake bite. AB - Until recently, hysteria was believed to be uncommon amongst the indigenous inhabitants of tropical Africa. Though snake bites are common, there has not been any previous report of hysterical manifestations following snake bite. We report a case of hysterical paralysis in a nulliparous Nigerian female, with comments on its diagnostic and prognostic implications in an ethnic community. PMID- 1496713 TI - Pregnancies too young, too old, too many and too frequent in Nigeria; prevalence and the effect on birthweight and perinatal mortality. AB - Among 2,865 consecutive singleton deliveries at Ilorin, Nigeria, high-risk pregnancies classified as too young, 206 (7.2%); too old, 74 (2.6%); too many, 234 (8.2%): too frequent, 216 (7.5%); and two or more variables 283, (9.8%) accounted for a total of 1013 (33.9%) deliveries. Low birth weight infants are significantly more among high-risk infants, 89 (8.8%), when compared to control infants, 87 (4.7%) (p less than 0.001). Similarly, the relative risk for perinatal mortality was 2.8 to 6.8 times higher among the high-risk pregnancies. A comprehensive programme offering family planning, education and economic opportunities is advocated for prevention. PMID- 1496714 TI - The use and efficacy of Azadirachta indica ADR ('Neem') and Curcuma longa ('Turmeric') in scabies. A pilot study. AB - In the Ayurvedha and Sidha system of medicine (Indian system of medicine) Azadirachta indica ADR ('Neem') and Curcuma longa ('Turmeric') has been used for healing chronic ulcers and scabies. The 'Neem' and 'Turmeric' was used as a paste for the treatment of scabies in 814 people. In 97% of cases cure was obtained within 3 to 15 days of treatment. We find that this is a very cheap, easily available, effective and acceptable mode of treatment for the villagers in the developing countries. We have noticed no toxic or adverse reaction so far. However, further research is needed. PMID- 1496715 TI - Chloroquine resistance of Plasmodium falciparum in Bukumbi, Tanzania. An in vivo study. AB - The sensitivity of Plasmodium falciparum to chloroquine was studied in 42 children in Bukumbi, Tanzania. The standard WHO in vivo test was used, and chloroquine phosphate 25 mg base/kg was administered in divided doses over three days. From the 42 patients 13 (31%) were sensitive to chloroquine and 29 (69%) had not cleared their parasites on day 7. From the resistant cases, 1 showed RI resistance (early recrudescence), 6 showed RII resistance and 18 cases showed RIII resistance. Four were resistant, not further specified. This high degree of resistance might indicate that chloroquine, without control of the intake and uptake, is no longer the drug of choice for this area. PMID- 1496716 TI - Schistosomiasis in the Yemen Arab Republic. Prevalence of Schistosoma mansoni and S. haematobium infection among schoolchildren in the central highlands and their relation to altitude. AB - A study was carried out in March/April 1988 to determine the prevalence of Schistosoma haematobium and S. mansoni among schoolchildren in the Jebal ash Sharq District, Dhamar Governorate, Yemen Arab Republic. The average percentage of schoolchildren infected with schistosomies (one or both species) was 34.5%. The prevalence of S. mansoni was found to be 22.6% and S. haematobium was present in 16.8% of the urine samples. A negative correlation was found between prevalence and altitude. PMID- 1496717 TI - The white cell count in typhoid fever. AB - Leucopenia with neutropenia and a relative lymphocytosis are believed to be common findings in patients with typhoid fever. This paper reviews 191 adult patients with typhoid. The total and differential leucocyte counts done on admission were analysed. In this study leucopenia was found in only 24.6% of patients. Whilst complications occurred at any white cell count, the prevalence of complications increased significantly to 70% in patients with a white cell count above 8 x 10(9)/l. Neutropenia was found in 25% of patients, and none of the patients had an absolute lymphocytosis, whereas 75.8% of patients had true lymphopenia. PMID- 1496718 TI - Leprosy among university and high school students in Benin City, Nigeria. A eight years review. AB - 36 cases of leprosy were seen among University and High School students in the Skin Clinic of the University of Benin Teaching Hospital during an 8 years period (1982-1989). The male to female ratio was 2 to 1. Borderline tuberculoid and tuberculoid leprosy were the commonest form of presentation, seen in 66.6% of all cases. Borderline lepromatous and lepromatous leprosy were seen in 22% while indeterminate in 11% of cases. There has been a gradual reduction of new cases from a peak of about 8 cases in 1983 to one in 1989. Most patients complied with treatment and were able to continue their education with little or no hinderance. PMID- 1496719 TI - Prolonged undiagnosed fever in northern India. AB - A prospective study for five years along with a retrospective analysis of all patients admitted over 10 years with the diagnosis of prolonged undiagnosed fever was carried out in a referral hospital of North India to determine the specific disorders responsible for it. One hundred and fifty patients (80 prospective and 70 retrospective) were included in the study. Infections, especially tuberculosis, was the most dominant cause (50%), followed by lymphoreticular and haematological disorders (21.32%), collagen vascular disorders and neoplasms (8.67%) each. Miscellaneous causes were responsible in 6.67% and in 4.67% the cause of fever remained undiagnosed. PMID- 1496720 TI - Anti-thrombin III deficiency in Nigerian children with sickle cell disease. Possible role in the cerebral syndrome. AB - A prospective study of Nigerian children with sickle cell disease was undertaken to determine serum levels of antithrombin III (AT-III) and compare these with normal controls. Mean serum AT-III was significantly lower in patients than in controls (14.51 +/- 4.84 mg/dl and 17.75 +/- 5.92 mg/dl) respectively. Seven of the 49 sickle cell patients had AT-III levels below 50% of normal values. Mean platelet counts were significantly higher in sicklers than in normal controls. AT III deficiency may predispose to thrombotic complications in children with sickle cell disease. PMID- 1496721 TI - The pathological basis of chronic renal failure in Nigerians. An autopsy study. AB - With the aim of determining the relative prevalence of the diseases underlying chronic renal failure (CRF) in a large homogeneous black tropical population, the autopsy records of the Obafemi Awolowo University Teaching Hospital over a four year period were studied. Out of a total of 702 cases coming to autopsy during this period, 66 (9.4%) died as a result of CRF. The highest number of cases of CRF fell within the 31-40 year age group with a male/female ratio of 1.28:1. Chronic glomerulonephritis was responsible for 40.9% of cases, malignant nephrosclerosis 16.6%, benign nephrosclerosis 7.6% while endstage renal disease (ESRD) was responsible for 15.4%. A miscellaneous group of diseases was responsible for 19.7%, about half of which was due to chronic pyelonephritis. Rarer causes of CRF were diabetic nephropathy, multiple myeloma, systemic lupus erythematosus and analgesic nephropathy. PMID- 1496722 TI - Haematological nutrition of schoolchildren in the far northwestern cape. AB - The prevalence of anaemia and deficiencies of iron, folate and vitamin B12 were investigated in primary schoolchildren of mixed ethnic origin living in four towns in a remote semi-desert area of southern Africa, the Richtersveld. Anaemia was uncommon (6.3%); iron and vitamin B12 deficiencies were not observed. Sub normal erythrocyte folate concentrations were present in 14.5%, but significant folate deficiency was rare (less than 2%). There were negligible differences in the haematological parameters of the children in the four towns, even though children living in Kuboes received milk at school and children at Dryfsandt a lunch of milk, brown bread and margarine. The results support the general observation that schoolchildren are not a risk group for nutritional anaemia. PMID- 1496723 TI - Evaluation of community health services utilization. A case study from Columbia. AB - In a PHC project in Choco, Columbia, Community Health Workers (CHWs) were trained in curative care of some simple diseases. Consultations were registered in a village-based monitoring system. Of registered cases, about 60% was treated by CHWs and 15% referred by them. Episodes were underregistered. A cross-sectional survey was carried out in 6 villages, among 890 persons. The CHW was consulted in 6.5% of the cases in which a consultation had been made. This low percentage of consulting the CHW is explained by the lack of perception of all diagnosed morbidity. Reasons for low consultation rates were found in a household survey. Suggestions on improvement of the utilization of CHW services are presented. PMID- 1496724 TI - Post-operative transfusion malaria. AB - Two Saudi patients who underwent cardiac surgery, developed fever after being discharged from hospital. Both received blood transfusion during operation. The cause of fever was found to be due to malaria acquired from the transfused blood. As no single measure could prevent transfusion malaria, clinical awareness of the condition should lead to early diagnosis and management of such cases. PMID- 1496725 TI - A case of fatal gastrointestinal strongyloidiasis in an otherwise healthy Nigerian, masquerading as gastric outlet obstruction. AB - A 46-year old man who presented with signs and symptoms suggestive of gastric outlet obstruction from carcinoma or cicatrisation of chronic duodenal ulcer is presented. The radiologic as well as laboratory findings confirmed strongyloidiasis. The lesion which has been associated with immunodeficient patients was found in an otherwise healthy patient. It is for this reason and the need to heighten the awareness of practising doctors to the salient radiologic features, that this report is presented. PMID- 1496726 TI - Tracheal papilloma presenting as asthma in a child. AB - This report describes a child with a tracheal papilloma who was initially diagnosed and treated as having asthma. The case illustrates that all wheezing in children should not be attributed to asthma. PMID- 1496727 TI - Multifocal Salmonella splenic abscess in a HIV-infected patient. AB - A case of spleen abscess complicating Salmonella bacteremia in a HIV-infected patient is reported for the first time. Chronic pancreatitis and the infection of a pre-existing pseudocyst of the pancreas tail might have been the predisposing factor. Infection developed before other AIDS criteria were evident in the patient. Splenectomy plus antibiotic therapy was required to eradicate the process. Salmonella enteritidis was cultured from two suppurated lesions of the excised organ. PMID- 1496728 TI - Giant hemangioma of the liver. An observation from Samoa Islands. AB - Hemangioma of the liver is a benign tumor of vascular origin. Most of them are less than 2-3 cm in diameter and remain asymptomatic. Although hemangioma is the most frequent benign tumor of the liver large symptomatic hemangiomas, so-called 'giant' hemangiomas, are rare. In this paper a case of 'giant' hepatic hemangioma measuring 15 cm in diameter, seen in a middle aged Samoan woman, is presented. Clinical, pathological and therapeutical features are discussed. PMID- 1496729 TI - The treatment of adult hyperglycaemia in an African rural hospital. AB - This paper describes the treatment of adult diabetic ketoacidosis in an African rural hospital in which there were only rudimentary diagnostic facilities. It is intended to be a practical guide to doctors working under similar conditions. It also deals with some of the pathophysiological mechanisms underlying diabetic ketoacidosis but emphasises the use of clinical skills in patient assessment and management. PMID- 1496730 TI - Can mothers safely prepare labon-gur salt-sugar solution after demonstration in a diarrhoeal hospital? AB - Home-based salt-sugar solution (SSS) prepared with labon (locally produced sea salt) and gur (unrefined brown sugar) has been recommended as a cheap, locally available and a simple tool to prevent and treat diarrhoeal dehydration. Preparation of labon-gur SSS is demonstrated to the patients and the attendants at ICDDR, Bangladesh. To evaluate performances, 150 mothers were asked to measure labon and gur by finger pinch and first method and 100 mothers measured half a seer of water to prepare labon-gur SSS, shortly after the demonstration sessions. 4.0% of the samples exceeded the upper safety limit while 1.3% exceeded the upper danger limit for salt and 98.7% samples of gur were within safe and effective range. Mothers' performances were not different with regard to their educational status and prior practice at home. 80% knew about the solution before coming to the hospital and 45% had utilized this knowledge. Our study suggests that demonstration of home-based SSS in a diarrhoeal hospital may positively affect health education and that health personnel should actively participate in increasing health awareness. PMID- 1496731 TI - Evaluation of 5.1-[NANP]19, a recombinant Plasmodium falciparum vaccine candidate, in adults. AB - In a randomized single-blind study, 13 healthy adult volunteers were subcutaneously immunized with 2 or 3 single 50 or 400 micrograms doses of a Plasmodium falciparum recombinant vaccine candidate designated 5.1-[NANP]19. The vaccine caused transitory reactions at the injection site. Eight (62%) volunteers had a greater than or equal to 4-fold increase of antibody titer against sporozoites in immunofluorescence assay, all 13 seroconverted in IgG enzyme linked immunosorbent assay against [NANP]50 antigen, and in 6 (46%) a lymphocyte proliferation index greater than or equal to 3 against 5.1 antigen was observed. Seven volunteers were challenged with mosquitoes infected with P. falciparum. All developed detectable parasitemia after 7 to 12 days and all received drug therapy within 24 hours. One volunteer with a cellular response to 5.1 had two negative in vitro parasite cultures before treatment, despite overt parasitemia. He was the only challenged volunteer who remained free of malaria symptoms. PMID- 1496732 TI - Malaria parasite density and body temperature in children under 10 years of age in Calabar, Nigeria. AB - 1,188 children under 10 years of age who attended the children's Emergency Clinic were examined from January to December 1988. Their axillary temperatures were recorded and thick and thin blood smears made to determine the malaria prevalence rate and the parasite density. The results show a high prevalence rate (44.8%) for malaria and this was stable throughout the year. The number of subjects with parasite densities of 100,000/mm3 and over, increased progressively with increase in body temperature such that 74.9% of the parasitemic subjects had high grade temperatures of 38 degrees C and over, while only 11.8% had moderate temperatures of 37.5-37.9 degrees C. The ratio of parasitemic afebrile to parasitemic febrile patients was in the order of 1:6, suggesting that parasitaemia is usually accompanied by fever. There was a steady rise in temperature with parasite density up to 39.5 degrees C, when further increase in parasite density apparently caused no further rise in temperature, suggesting a self-protective efficient feed back mechanism. PMID- 1496733 TI - [Acute delusional psychoses and the new classifications]. PMID- 1496734 TI - [Psychosomatic approach in a self-induced dermatitis]. PMID- 1496735 TI - [Echocardiographic study of the distribution of myocardial hypertrophy in primary hypertrophic cardiomyopathies]. PMID- 1496736 TI - [Syndrome of anorectal mucous prolapse]. PMID- 1496737 TI - [The optic disc in mass screening of chronic open-angle glaucoma]. PMID- 1496738 TI - [Infection profile of the hospitalized diabetic patient: 135 cases]. PMID- 1496739 TI - [Prognosis of purulent meningitis in the infant and young child]. PMID- 1496740 TI - [Lipid evaluation of coronary patients before and after physical rehabilitation]. PMID- 1496741 TI - [ Lipids--lipoproteins--apolipoproteins--risk markers in atherosclerosis]. PMID- 1496742 TI - [Congenital adrenal hyperplasia by deficiency of 11 beta hydroxylase]. PMID- 1496743 TI - [Liver transplantation]. PMID- 1496744 TI - [Evaluation of a decade of puva therapy in Tunis]. PMID- 1496745 TI - [Cerebral computed tomographic scanning in 43 cases of tuberculous meningitis]. PMID- 1496746 TI - [Results of protein profile in glomerulopathies]. PMID- 1496747 TI - [High resolution cytogenetic techniques or microcytogenetics]. PMID- 1496748 TI - [Psychiatric emergencies at the University Hospital Center of Monastir]. PMID- 1496749 TI - [P.O.E.M.S. syndrome, a Tunisian case]. PMID- 1496750 TI - [A diagnostic trap: pulmonary sequestration, value of the computed tomographic scan]. PMID- 1496751 TI - [Hyperactivation of the mononuclear phagocyte system and typhoid fever]. PMID- 1496752 TI - Platelet count in deep saturation diving. AB - Platelet counts were measured in 10 divers during the course of 4 experimental deep dives (450 and 600 m) and different anticoagulants were tested. The use of sodium citrate as an anticoagulant was associated with artifactual thrombocytopenia, whereas ethylenediaminetetraacetic acid proved to be satisfactory. During one of the dives (450 m) the use of fluorocarbon to remove excess dissolved inert gas before decompression of the samples was systematically tested. Mean platelet count decreased from 272,600 +/- 29,400 mm-3 (mean +/- SD) on Day 7 (450 m) to 177,700 +/- 26,400 mm-3 on Day 12 (360 m). Platelet count had recovered to 209,900 +/- 20,700 mm-3 at the time of surfacing. Mean hematocrit (expressed in percent) increased from 44.7 +/- 2.2 predive to 59.4 +/- 2.0 on Day 7 (450 m) to 40.9 +/- 2.8 at the time of surfacing. These changes were statistically significant (P less than 0.05). Platelet counts on samples that had been degassed with fluorocarbon were not different from samples that had been decompressed without degassing. PMID- 1496753 TI - Renal responses during a dry saturation dive to 450 msw. AB - Four subjects were compressed to a simulated depth of 450 msw (46 bar) for 37 days in the main research chamber of the German underwater simulator diving facility at the GKSS Research Center, Geesthacht. The ambient gas was trimix. Urine was collected at 0700, 1300, and 1900 h each day for analysis of Na+, K+, volume, osmolality, and creatinine. Urine, antidiuretic hormone (ADH), and aldosterone were analyzed separately. Daily fluid, Na+, and K+ intake were analyzed throughout the dive. The aim of the investigation was to confirm the existence of a diuresis and natriuresis which had been observed in earlier saturation dives to 31 atm abs using He-O2. A significant diuresis was observed during compression despite a decrease in fluid intake. After compression the diuresis decreased somewhat but remained significantly above precompression control levels during the entire hyperbaric exposure. No significant change in fluid intake was observed. Daily Na+ and K+ excretion increased significantly during compression, which was accompanied by a significant increase in nocturnal excretion of Na+ and K+. Daily intake of Na+ and K+ decreased throughout the dive. Daily urine ADH decreased immediately upon compression and was associated with a parallel decrease in urine osmolality. In contrast, urinary aldosterone excretion exhibited no change during the dive despite the increase in Na+ and K+ excretion and decrease in Na+ intake. PMID- 1496754 TI - [44th meeting of the German Society for Urology. Munich, 9-12 September 1992. Abstracts]. PMID- 1496755 TI - Evaluation of an atrophic rhinitis vaccine under controlled conditions. AB - A vaccine containing inactivated cultures of Bordetella bronchiseptica, toxigenic Pasteurella multocida type D and dermonecrotic P multocida type D toxoid in an oil-in-water adjuvant was given to seven sows, with seven others acting as controls. Half the piglets in each litter were exposed intranasally when four days old to B bronchiseptica and when eight days old to toxigenic P multocida type D. There was considerably less sneezing in the litters of the vaccinated sows and when the piglets were 10 weeks old, only 18 per cent had deformed snouts compared with 74 per cent in the litters of the control sows. The average liveweight gain of the piglets born to vaccinated sows was significantly better (P less than 0.05) between two and 10 weeks of age than that of the piglets born to unvaccinated sows, although there were no significant lower respiratory tract lesions in either group. The conchal atrophy scores were significantly lower (P less than 0.001) in the piglets from the vaccinated sows and were negatively correlated (r = -0.37) with increasing liveweight gain. In the liters of the vaccinated sows, P multocida was not isolated from the nasal passages of the in contact piglets and from only 7 per cent of those deliberately exposed compared with 65 per cent and 79 per cent, respectively, in the litters of the control sows. P multocida was isolated post mortem from the tonsils of 23 per cent of the piglets of vaccinated sows and from 87 per cent of those from unvaccinated sows. PMID- 1496756 TI - Enterococcus hirae in septicaemia of psittacine birds. PMID- 1496757 TI - A 49, XO sterile murrah buffalo (Bubalus bubalis). PMID- 1496758 TI - Clinical teaching. PMID- 1496759 TI - Clinical teaching. PMID- 1496760 TI - Docking of dogs. PMID- 1496761 TI - Docking of dogs. PMID- 1496762 TI - Outbreak of lameness in cattle. PMID- 1496763 TI - Resistance to avermectins and milbemycins. PMID- 1496764 TI - Distemper vaccination in ferrets. PMID- 1496765 TI - Cystostomy in a cat with urethral trauma. PMID- 1496766 TI - Economic realism and practice fees. PMID- 1496767 TI - Vaginal prolapse in ewes. PMID- 1496768 TI - Causes of mortality and parasites and incidental lesions in dolphins and whales from British waters. AB - Detailed post mortem examinations were carried out on 18 dolphins and whales found dead on the coast of the United Kingdom. The commonest causes of death were pneumonia and entanglement in fishing gear. Of the non-fatal conditions, parasitoses of various organs were common and there was a wide variety of other conditions. In total 124 diseases and other lesions were found, giving an average of 6.9 conditions per animal. PMID- 1496769 TI - Treatment and control of sheep scab (Psoroptes ovis) with ivermectin under field conditions in South Africa. AB - Four trials including 11,266 sheep were conducted in South Africa to evaluate the efficacy of the systemic parasiticide ivermectin against field outbreaks of sheep scab (Psoroptes ovis) when two doses of approximately 200 micrograms/kg were administered subcutaneously seven days apart (days 0 and 7). As sheep scab is a notifiable disease in South Africa, it was not possible to include an untreated control group. The prevalence of clinically affected animals in the four treated flocks varied from 0.4 per cent to 99 per cent before the two treatments. After the treatments, there were no signs of active clinical infection in any of the sheep between days 28 and 30, or at subsequent examinations. P ovis mites were recovered from scrapings from 114 of 127 indicator sheep before the treatment but no mites were recovered from them between days 28 and 30 or 42 and 58 after the treatments. PMID- 1496770 TI - Thoracic spinal calcinosis circumscripta causing cord compression in two German shepherd dog littermates. AB - Two young German shepherd dog littermates had progressive, painless, hindlimb ataxia. In both dogs plain radiography of the vertebral column revealed a solitary mineralised lesion on the dorsal laminae between the dorsal spines of the second and third thoracic vertebrae, and myelography with iopamidol demonstrated cord compression at the level of the lesions. The first dog died 18 hours after the myelography. A dorsal laminectomy performed in the second dog resulted in neurological improvement. A histopathological examination confirmed that both lesions were calcinosis circumscripta. The cause of the death of the first dog was meningitis. PMID- 1496771 TI - Electron microscopy and pedigree study in an Ayrshire bull with tail-stump sperm defects. PMID- 1496772 TI - Morbillivirus infection in a striped dolphin (Stenella coeruleoalba) from the coast of Italy. PMID- 1496773 TI - Docking of dogs. PMID- 1496774 TI - Use of Xylocaine pump spray in cats. PMID- 1496775 TI - Verotoxigenic Escherichia coli 0.157 in Scottish calves. PMID- 1496776 TI - Ivermectin in ovine parasite control. PMID- 1496777 TI - Calf exports and Salmonella typhimurium incidents in UK calves. PMID- 1496778 TI - Preliminary development of a live drug-controlled vaccine against bovine babesiosis using the Mongolian gerbil, Meriones unguiculatus. AB - This study investigated the practicality and potential of the gerbil, Meriones unguiculatus, as a source of live Babesia divergens vaccine and also as a model for the use of the vaccine in cattle. A series of experiments with gerbils concerning vaccine infectivity, immunogenicity and safety were carried out. It was concluded that the use of RPMI medium/40% foetal calf serum as a diluent improved vaccine infectivity, but that the parasitaemia of the blood obtained from donor gerbils had little or no effect. The immunostimulants levamisole and killed Corynebacterium parvum improved vaccine immunogenicity and it was also shown that the subcutaneous route of infection resulted in the greatest host response. Control of vaccine virulence with drugs was only possible when drugs with prophylactic properties, such as imidocarb and long-acting oxytetracycline, were used. More studies are required on all these topics, particularly with regard to their applicability to cattle, and also concerning the possible attenuation of the parasite by manipulation in the gerbil host. PMID- 1496779 TI - A specific DNA probe which identifies Babesia bovis in whole blood. AB - A genomic library of Babesia bovis DNA from the Mexican strain M was constructed in plasmid pUN121 and cloned in Escherichia coli. Several recombinants which hybridized strongly to radioactively labeled B. bovis genomic DNA in an in situ screening were selected and further analyzed for those which specifically hybridized to B. bovis DNA. It was found that pMU-B1 had the highest sensitivity, detecting 25 pg of purified B. bovis DNA, and 300 parasites in 10 microliters of whole infected blood, or 0.00025% parasitemia. pMU-B1 contained a 6.0 kb B. bovis DNA insert which did not cross-hybridize to Babesia bigemina, Trypanosoma evansi, Plasmodium falciparum, Anaplasma marginale, Boophilus microplus and cow DNA. In the Southern blot analysis of genomic DNA, pMU-B1 could differentiate between two B. bovis geographic isolates, Mexican strain M and Thai isolate TS4. Thus, the pMU-B1 probe will be useful in the diagnosis of Babesia infection in cattle and ticks, and in the differentiation of B. bovis strains. PMID- 1496780 TI - The epidemiology of toxoplasmosis on Iowa swine farms with an emphasis on the roles of free-living mammals. AB - Multiparous sows from 19 central Iowa swine farms were tested for antibodies against Toxoplasma gondii by the modified direct agglutination test. Antibody titers of 1:32 or greater were considered positive. Rodents, domestic cats, opossums (Didelphis virginiana), raccoons (Procyon lotor) and striped skunks (Mephitis mephitis) were live-trapped on each farm and similarly tested for antibodies. The overall prevalence of T. gondii antibodies in the species tested was 39/273 (14.3%) swine, 31/74 (41.9%) cats, 2/588 (0.3%) house mice (Mus musculus), 0/21 mice of the genus Peromyscus, 0/9 Norway rats (Rattus norvegicus), 1/34 (2.9%) opossums, 4/14 (28.6%) raccoons and 2/7 (28.6%) striped skunks. The overall prevalence was significantly greater in adult cats versus juvenile cats, adult male cats versus adult female cats, and adult raccoons versus juvenile raccoons. The prevalence of T. gondii antibodies in sows was compared with the prevalence in each non-swine species on a farm basis in order to identify existing associations. The prevalence in sows (and each of the non swine species) was also analyzed on a farm basis for association with farm characteristics or swine management practices, including the degree of confinement of swine, population size and average parity of breeding female swine, estimated cat population size, and estimated mouse and rat abundance. Average titers of seropositive animals were compared on a species basis. The prevalence in sows which were totally and continuously confined was lower than that in sows which were not totally and continuously confined. The prevalence in sows from farms with an average parity of less than 2.0 was significantly lower than that in sows from farms with an average parity of 2.0 or greater. These results suggested that the prevalence of T. gondii antibodies in swine increased with age and that prevalence in swine could be reduced through total confinement. No associations could be established between prevalence in sows and prevalence in non-swine species or other farm characteristics/swine management practices. However, the high prevalence of T. gondii antibodies in cats suggested that fecal contamination of the environment by cats may be the most significant source of toxoplasmosis for swine. The extremely low prevalence of T. gondii antibodies in house mice suggested that this species was not an important source of T. gondii for swine in Iowa. PMID- 1496781 TI - Relationships between trypanosome infection measured by antigen detection enzyme immunoassays, anaemia and growth in trypanotolerant N'Dama cattle. AB - Relationships were evaluated between trypanosome infection as measured by antigen detection enzyme immunoassays (antigen ELISA), anaemia as determined by average packed red cell volume (PCV), and animal performance as assessed by daily weight gain in 99 N'Dama cattle in Gabon exposed to natural tsetse challenge at 11.5 months of age and recorded 14 times over a 13 week period. Approximately half the animals were found to be infected for an average of five of the 14 times that they were examined: 38% with Trypanosoma congolense, 13% with Trypanosoma vivax and 49% with a mixed infection. Trypanosoma congolense infections had significant deleterious effects on animal growth, while T. vivax infections did not. Animals found on several occasions to be infected with T. congolense had significantly lower PCV values than those demonstrated to be infected on fewer occasions. No relationship was found between mean optical density (OD) values in antigen ELISA and PCV values. Animals capable of maintaining PCV values, even when antigen ELISA positive on a high number of occasions, grew at the same rate as uninfected animals. Animals that could not maintain PCV values when infected had poorer growth. Antigen ELISA has the potential to increase the efficiency of selection of trypanotolerant N'Dama cattle under tsetse challenge in the field, in three main ways. (1) Accurate identification of trypanosome species, especially in mixed species infections, clarifies relations between infection, anaemia and animal performance. (2) Detection of animals antigenaemic without patent parasitaemia could allow individuals with superior ability to control trypanosome infection to be identified. (3) More accurate measurement of the proportion of time an animal is infected allows more accurate evaluation of its anaemia control capability. PMID- 1496782 TI - Immunisation of cattle against theileriosis in Nakuru District of Kenya by infection and treatment and the introduction of unconventional tick control. AB - One hundred and one cross European-Boran cattle (50 cows and 51 calves), on a farm in Nakuru District, Kenya, were immunised against theileriosis using Theileria parva lawrencei and Theileria parva parva stocks from another district of Kenya. The stabilates used were T.p.lawrencei (Mara III) used at 10(-1.7) dilution and T.p.parva (Kilae) used at 10(-1.0) dilution. The stabilates were combined and inoculated simultaneously with a short-acting formulation of oxytetracycline hydrochloride given intramuscularly at 10 mg kg-1 body weight and was repeated on Day 4 after inoculation of the stabilate. Most of the theileriosis challenge on the farm was thought to be derived directly from the African buffalo (Syncerus caffer). Nine percent of the cattle had significant indirect fluorescent antibody (IFA) titres before the immunisation and 99% after immunisation. The immunised cattle were exposed to tick-borne disease challenge on the farm by withdrawal of acaricide cover. The immunised cattle were divided into five groups plus two susceptible control cows and two calves for each group. Cattle in four of the groups had acaricidal ear tags, each group having a different type, applied to both ears and the fifth group remained untagged. The animals remained without conventional acaricide application for 134 days. Ten out of 20 (50%) non-immunised control cattle became T.p.lawrencei reactors which only one out of 97 (1%) of the immunised cattle reacted. A frequent complication noted was mild infections due to unidentified Theileria sp. which required expert differentiation from T.parva infections. An additional group of ten steers whose tick load was removed by hand at weekly intervals was introduced 79 days after exposure; these had no tick control and four became T.p.lawrencei reactors. Of 12 calves born during the exposure period and without tick control, four became theilerial reactors and one died. The application of acaricidal tags however, reduced tick infestation levels considerably compared with untagged controls but did not prevent transmission of theileriosis with the possible exception of tags on Group 4. A number of transient low grade fevers were noted and attributed to Theileria sp., Ehrlichia bovis, Ehrlichia (Cytoecetes) ondiri and Borrelia theileri infections, none of which were fatal. One immunised animal died of acute dual infection of Babesia bigemina and Borrelia theileri after acaricide control by spraying was re-introduced but no Anaplasma infections were detected. An analysis of the economic effects of immunisation was made. PMID- 1496783 TI - Epizootiology of fascioliasis in Montana. AB - During 1989-1990, the United States Department of Agriculture (USDA) meat inspection records were used to determine the distribution and incidence of liver flukes (Fasciola hepatica and Fascioloides magna) in Montana cattle. Of the cows and bulls slaughtered in USDA-inspected packing plants during a 12 month time period, 17.24% had livers that were condemned because of liver flukes. This was a 12% increase over USDA liver condemnations reported for 1973. Infected animals have been reported from 26 counties in Montana, mostly located in the south central and western half of the state. Forty-nine percent of the 2.4 million cattle in Montana are raised in these counties. Lymnaeid snail species that may serve as intermediate hosts for Fasciola hepatica were found in most of the counties where liver flukes were reported. The principal vectors believed to be responsible for the transmission of Fasciola hepatica in Montana are species of the genus Fossaria. Stagnicola montanensis and Lymnaea stagnalis, which may serve as intermediate hosts for this parasite have also been collected. A known intermediate host for Fascioloides magna, Stagnicola caperata, was also found in several locations. PMID- 1496784 TI - Sudden death of calves by experimental infection with Strongyloides papillosus. I. Parasitological observations. AB - Recently, an unknown disease, 'sudden death', in calves has been found in Japanese beef production farms. A previous study conducted by Taira and Ura indicated that sudden death can be effected in calves by hyperinfection of Strongyloides papillosus (SPL) and that the disease is possibly caused by SPL infection. In the present work, an experimental infection of SPL in calves was conducted to confirm the field occurrence. Fifteen Holstein Friesian calves, ranging from 45.5 to 85.6 kg in body weight, were divided into six groups. Calves of Groups A, B, C, D, E and F were infected once at the rate of 100,000, 320,000, 1,000,000, 3,200,000, 10,000,000 and 32,000,000 SPL larvae per 100 kg of body weight, respectively. Five calves were assigned to Group B, while two calves were assigned to the other groups. After showing no premonitory signs, sudden death of ten calves took place. The survival time of these calves was 27.4 and 16.8 days (Group B), 14.8 and 14.8 days (Group C), 13.3 and 14.2 days (Group D), 11.0 and 11.1 days (Group E) and 11.6 and 10.8 days (Group F). Three calves of Group B did not exhibit sudden death. The results of this study demonstrate that strongyloidiasis was the cause of sudden death. PMID- 1496785 TI - Evaluation of ivermectin against experimental infections of Haemonchus contortus and Trichostrongylus colubriformis in goats. AB - Fourteen nematode parasite-naive kids were given a mixed larval inoculum (approximately 17,250 infective larvae) via stomach tube. Twenty-two days after infection, the kids were randomly assigned to control and treatment groups of seven animals each. Mean eggs per gram for control and treatment groups were 4304 and 5315, respectively. Kids in the treatment group were given ivermectin (0.2 mg kg-1) administered by subcutaneous injection. At necropsy, the mean numbers of Haemonchus contortus and Trichostrongylus colubriformis for control and treatment groups were 2259 and 0, and 3033 and 773, respectively. This reduction was significant (P less than 0.05) for both species, resulting in an efficacy of 100.0% and 74.5%, respectively. The lower efficacy against T. colubriformis may be a sign of resistance, a reduced effectiveness due to route of administration, or a higher dose may be required with subcutaneous administration, as has been observed previously. PMID- 1496786 TI - Renal involvement in mice experimentally infected with Toxocara canis embryonated eggs. AB - Histological examination of kidneys from mice experimentally infected with Toxocara canis embryonated eggs demonstrated the presence of a segmental or diffuse mesangioproliferative glomerulonephritis. Immunohistochemical studies established that renal alterations were associated with glomerular deposits of IgG, IgM and third component of complement (C3). These findings suggest that an immunomediated mechanism might possibly be involved in the genesis of kidney damage observed in mice infected with T. canis embryonated eggs. PMID- 1496787 TI - A new anthelmintic assay using rats infected with Trichostrongylus colubriformis. AB - A new anthelmintic assay is described which uses immunosuppressed (60 ppm hydrocortisone acetate in diet) rats infected with the nematode Trichostrongylus colubriformis. Immunosuppressed rats were infected with 1500 T. colubriformis larvae, treated either orally or subcutaneously on Day 14 post-infection and necropsied 4 days after treatment. The worm counts in immunosuppressed control animals averaged 775 worms per rat. A range of benzimidazoles, levamisole hydrochloride, morantel tartrate, 22,23-dihydroavermectin B1a and alpha milbemycin have been evaluated in the assay. The ED95 values obtained indicate that rats infected with T. colubriformis provide a highly predictive model for assaying the activity of experimental drugs in vivo prior to studies in ruminants. PMID- 1496788 TI - Epidemiological study of parasite infection in a cow-calf beef herd in Quebec. AB - The patterns of gastrointestinal and pulmonary nematode infections in a previously untreated Aberdeen Angus cow-calf herd were observed between May 1988 and December 1990. The cow-calf herd and replacement heifers were on separate pastures. The relatively high mean faecal egg counts of cows and heifers at the time of turnout were mainly owing to the maturation of hypobiotic worms. The strongyle egg counts of calves began to rise soon after turnout onto pasture and reached peak levels at the end of the grazing season. The number of infective larvae on pasture was highest during September/October. Ostertagia, Cooperia and Nematodirus were the most prevalent genera found at necropsy and on pasture. Larvae of these nematodes were able to overwinter on pasture and Ostertagia larvae, additionally, were able to overwinter in the host as arrested early fourth stage larvae. The high egg output of cows at the time of turnout may serve as a source of infection for their calves and be responsible for the late-season rise in pasture larval counts. PMID- 1496789 TI - The effect of ivermectin treatment against inhibited early third stage, late third stage and fourth stage larvae and adult stages of the cyathostomes in Shetland ponies and spontaneous expulsion of these helminths. AB - A controlled and critical test on the efficacy of ivermectin against larval and adult stages of the cyathostomes was carried out in six yearling castrated male Shetland ponies. The ponies grazed together as one group from 3 May to 4 October 1990, after which they were housed. Three ponies were treated with ivermectin on 29 October while the others served as controls. The shedding of helminths in the faeces was followed in all ponies until necropsy on 14 November. Comparison of worm counts of both groups before and after necropsy showed no evidence for an effect of ivermectin against inhibited early third stage larvae (EL3) and mucosal late third stage (LL3) and fourth stage larvae (L4). However, a high, but not 100%, efficacy was observed against adults and lumenal L4. A remarkable observation was the high incidence of spontaneous expulsion of L4 and adult populations of some species in two of the untreated ponies. PMID- 1496790 TI - Observations on the New World screwworm fly in Libya and the risk of its entrance into Egypt. AB - Data on traumatic myiasis caused by Cochliomyia hominivorax in Libya were reported from August 1988 until February 1989. A total of 468 cases of screwworm myiasis were recorded in seven species of livestock and 229 humans, mainly children, were also found to be infested. Cattle and sheep were the most common hosts in livestock. In cattle, the principal infestation site was the umbilicus of neonates; in sheep, it was mainly the fatty tail. Animal myiasis reached its peak in October and November, but disappeared abruptly in winter on the onset of cold weather. Screwworm distribution was confined to the northwest of Libya. The potential dispersion of the fly from this area and the possibility of infestation of other countries, particularly Egypt, are discussed. Food and Agriculture Organization (FAO) efforts to confront the New World screwworm problem in Africa are mentioned. PMID- 1496791 TI - Fasciola hepatica: comparison of flukes from Korea and the United States by isoelectric focusing banding patterns of whole-body protein. AB - Comparisons were made between the flukes from Chonnam, Korea and Oregon, USA by isoelectric focusing (IEF) of whole-body protein. Adult Fasciola hepatica were recovered from bile ducts of Korean native cattle. Whole-body protein of the flukes was subjected to IEF, and the banding patterns of the fluke protein were compared with those of North American F. hepatica recovered from experimentally infected calves. The overall banding pattern of F. hepatica from Korea was essentially identical to that of F. hepatica from the United States. These results provide further support for the usefulness of this technique in differentiating Fasciola species in other geographical areas. PMID- 1496792 TI - Transformation of Theileria parva derived from African buffalo (Syncerus caffer) by tick passage in cattle and its use in infection and treatment immunization. AB - A sporozoite stabilate (St. 199) of Theileria parva was obtained by feeding nymphal Rhipicephalus appendiculatus on an African buffalo (Syncerus caffer) and was used to immunize cattle by the infection and treatment method. Nymphal ticks were applied to one of the steers 90 days later and it was shown that the resultant adult tick had become infected. Using tick/cattle passage, two passage lines of T. parva were established. By the fifth tick/cattle passage, the parasite stocks had changed their behaviour to that of T. parva derived from cattle as the parasite produced relatively high schizont parasitosis and piroplasm parasitaemia in cattle, and had become highly infective to ticks. At various passage levels the parasite populations were characterized by behaviour and by monoclonal antibodies against T. parva schizonts using infected cell culture isolates from cattle during acute infections. The monoclonal antibody profile showed little evidence of antigen change of the parasite during passage through cattle, which was confirmed in a two-way cross-immunity experiment using sporozoite stabilate derived from ticks obtained from the buffalo and fourth passage in cattle. The implication of these results, particularly in relationship to immunization of cattle against T. parva derived from buffalo, is discussed. PMID- 1496793 TI - Ascaris suum--vaccination of mice with liposome encapsulated antigen. AB - Vaccination with liposome encapsulated adult crude antigen with and without coencapsulated immunomodulator (levamisole) in a mice/larval Ascaris suum model provided protection against a challenge infection (2000 eggs) in mice immunised by immobilised antigen. The best results (88.9% protection) were obtained with a combination of two doses of liposome entrapped antigen with leamisole. Vaccination with liposome vaccine without modulator was slightly less effective (78.7% protection). A single dose of vaccine was ineffective (14.3% protection). Application of the soluble antigen without any adjuvants led to the enhancement of worm yield in lungs and liver. PMID- 1496794 TI - Acquired immune response of cattle exposed to buffalo fly (Haematobia irritans exigua). AB - Naturally acquired immunity to buffalo fly (Haematobia irritans exigua) infestation was examined in cattle. Animals exposed to flies had serum antibodies to buffalo fly antigens at levels that correlated with the intensity of exposure. Two weeks of intense exposure to buffalo fly induced an increase in peripheral blood eosinophil numbers and a concomitant rise in serum antibody levels in exposed animals. Antigens specific for antibody induced by natural exposure were identified using antisera from exposed cattle to probe Western blots of whole fly homogenate separated using SDS-PAGE. Similar immunoreactive bands were found with buffalo fly saliva. Immunoreactive proteins were partially purified from whole fly homogenates by anion-exchange chromatography. Fractions eluted from columns were screened using Western blots probed with serum from exposed animals. Exposed animals showed immediate hypersensitivity to partially purified antigens and to buffalo fly saliva. Flies which fed on exposed animals with high serum levels of antibody to fly antigens did not show greater mortality than flies fed on unexposed animals. PMID- 1496795 TI - Concurrent Hepatozoon canis and Toxoplasma gondii infections in a dog. AB - A female 1-year-old dog died suddenly and was submitted for necropsy. Numerous grey-tan-colored nodules were seen in the lungs, brain and lymph nodes. Microscopically, the predominant lesion was necrosis associated with numerous Toxoplasma gondii tachyzoites. The parasites reacted positively with anti-T. gondii serum in an immunohistochemical test. Schizonts of Hepatozoon canis were seen in sections of lymph nodes and the spleen. PMID- 1496796 TI - Clinical neosporosis in a 4-week-old Hereford calf. AB - Most reports of neosporosis associated with abortion in cattle are in dairy cattle and infected calves do not survive beyond 7 days of age. This paper reports neosporosis in a 4-week-old Hereford calf. The calf was full term and appeared clinically normal at birth. At 2 weeks of age, the calf had weakened and was unable to nurse unassisted. The calf was killed at 4 weeks because of paralysis. The primary lesions were in the brain and were associated with Neospora caninum tachyzoites. The diagnosis was confirmed by immunohistochemical staining with anti-Neospora rabbit serum. PMID- 1496797 TI - Biometrical observations on different strains of Trypanosoma evansi. AB - Biometrical studies on buffalo, bovine and canine strains of Trypanosoma evansi isolated from species in Madras, India, were carried out. The buffalo, bovine and canine trypanosomes varied significantly in total length and width. The buffalo strain had a greater free flagellum, total length and width compared with the canine strain. PMID- 1496798 TI - Theileria infection in camels (Camelus dromedarius) in Egypt. PMID- 1496799 TI - Further evaluation of the use of buparvaquone in the infection and treatment method of immunizing cattle against Theileria parva derived from African buffalo (Syncerus caffer). AB - Three experiments were undertaken to determine the efficacy of different doses of buparvaquone in the infection and treatment immunization of cattle against Theileria parva derived from African buffalo (Syncerus caffer). Two of these experiments also compared buparvaquone with standard doses of long- and short acting formulations of oxytetracycline. In addition, different dilutions of stabilates were used in the experiments. In the first experiment, a 10(-1.0) dilution of stabilate was used to infect groups of cattle treated with buparvaquone at doses of between 5 and 0.625 mg kg-1 body weight (bwt) on Day 0 after infection. All control cattle developed severe theileriosis and none of the treatment regimes (including those utilizing long-acting oxytetracycline) prevented the development of theileriosis. Treatment with buparvaquone at 2.5 mg kg-1 bwt or oxytetracycline gave the most satisfactory results. In the second experiment when the sporozoite dose was reduced to 10(-2.0) dilution, buparvaquone treatment at 5 and 2.5 mg kg-1 bwt and short- and long-acting formulations of oxytetracycline reduced reactions greatly. While all the oxytetracycline treated animals produced a serological response and were immune to a 50-fold higher challenge with the immunizing stabilate, several animals in the buparvaquone groups did not show a serological response and were not immune to challenge. In the third experiment, groups of cattle were infected with 10( 1.2), 10(-1.4) and 10(-1.6) dilutions of stabilate and were treated with 2.5 mg kg-1 bwt of buparvaquone. No animals developed severe theileriosis and all seroconverted. On homologous challenge, however, two out of 14 cattle showed severe reactions. It was concluded that further work on immunization using buparvaquone treatment at 2.5 mg kg-1 bwt and 10(-1.6) dilution of the stabilate would have to be carried out before such a system could be used in the field. PMID- 1496800 TI - Pathogenesis of intestinal cryptosporidiosis in conventional and gnotobiotic piglets. AB - The pathogenesis of intestinal cryptosporidiosis was studied in 52 conventionally reared and 20 gnotobiotically reared piglets by inoculation with different doses of Cryptosporidium parvum oocysts. The prepatent period of C. parvum in both groups of animals were variable, depending on the number of oocysts administered. The patent period of C. parvum in conventionally reared piglets was 8 or 9 days; in gnotobiotic piglets cryptosporidia were found in feces until Day post infection (DPI) 16, when the last piglet was necropsied. Cryptosporidiosis in conventionally reared piglets is a self-limited diarrheal disease associated with morphological changes within the intestine. The most severe lesion was seen in the posterior jejunum and ileum from DPI 3 to DPI 7, and consisted of villous atrophy, crypt hyperplasia and inflammatory infiltration in the lamina propria. In gnotobiotic piglets cryptosporidia induced severe enterocolitis which occurred at least until DPI 16. The characteristics of enteric lesions were similar to those found in conventionally reared piglets. Intestinal cryptosporidiosis in both groups of animals shifted in the course of infection in the caudal direction and terminated in the large intestine. Examination by scanning electron microscope showed that infected absorptive cells had thicker and longer microvilli than those on non-infected cells; neighboring non-infected cells were hypertrophic, bulbously protuberant with minute microvilli with no distinct intercellular borders. Numerous cryptosporidia in the heterotopic glandular epithelium in the submucosa of cecum and colon on DPI 9 and 10 were found. No differences in the location and degree of cryptosporidial infection between colostrum-fed and colostrum-deprived conventionally reared piglets were found. Sow's colostrum does not appear to protect piglets from C. parvum infection. The role of intestinal microflora in the pathogenesis of cryptosporidiosis in piglets is discussed. PMID- 1496801 TI - Camel (Camelus dromedarius) and sheep (Ovis aries) meat as a source of dog infection with some coccidian parasites. AB - Experimental infection of dogs with camel (Camelus dromedarius) meat resulted in infection of the dogs with Isospora canis, Hammondia heydorni and Sarcocystis cameli. The dogs fed sheep (Ovis aries) meat passed oocysts of Isospora canis, Isospora ohioensis and sporocyts of Sarcocystis spp. Extraintestinal stages were detected in the intestinal lymph node of a rabbit killed 4 days following inoculation with Isospora ohioensis oocysts. Dogs fed the rabbit (killed 4 days after inoculation with I. ohioensis) passed I. ohioensis oocysts in their faeces 8 days post-infection. PMID- 1496802 TI - Investigations of breakdowns in protection provided by living Babesia bovis vaccine. AB - Field investigations of protection afforded by live Babesia bovis vaccine in Australia revealed that a ninefold increase in vaccine failures occurred in the period from 1985 to 1990. Laboratory trials using 189 experimental cattle were conducted to evaluate the protection afforded by the Babesia bovis strain used in the commercial vaccine during this time. Four isolates from clinical cases of babesiosis in vaccinated cattle were assessed. The results showed that the strain used in the vaccine during the 5 year period was poorly protective against three isolates while a recently isolated and prepared vaccine strain was strongly protective. Circumstantial evidence is provided that indicates the vaccine failures were due to change in the field populations of Babesia bovis, rather than change in the strain used in the vaccine. Implications of the results for the future of Babesia bovis vaccines are discussed. PMID- 1496804 TI - Autoradiographic quantification of the efficacy of niridazole in mice infected with 75Se-labelled cercariae of Schistosoma mansoni. AB - The effects of the anti-schistosomal drug, niridazole, on the migration of Schistosoma mansoni larvae, biosynthetically radioisotope-labelled with 75[Se] selenomethionine, was evaluated by autoradiography of compressed tissues of mice treated daily from Days 6 to 10 post-infection with 200 mg kg-1 niridazole. The results were compared with the migration of schistosomula in untreated controls. The distribution of schistosomula was altered in niridazole-treated mice, where there was a delayed migration from the lungs relative to the controls and significantly fewer schistosomula in total appeared to reach the liver. The total percentage of schistosomula detected as autoradiographic foci was significantly lower in treated mice than in the untreated controls. Niridazole-treated mice were free of any foci 10 days after the last treatment and no adult worms were recovered on perfusion of the hepatic portal system relative to control mice from which 5.8% of the infective cercariae were recovered as adult worms at Day 42 post-infection. PMID- 1496803 TI - Prevalence of antibodies to Toxoplasma gondii and Trichinella spiralis in 509 pigs from 31 farms in Oahu, Hawaii. AB - Serum samples from 509 pigs from 31 farms in Oahu, Hawaii were examined for antibodies to Toxoplasma gondii using the agglutination test in dilutions of 1:25, 1:50, and 1:500 and for Trichinella spiralis using the enzyme-linked immunosorbent assay. Toxoplasma gondii antibodies were found in 48.5% of pigs. Antibody titers were: 5.1% positive at 1:25 dilution, 28.6% positive at 1:50 dilution and 14.7% positive at 1:500 dilution. The prevalence of Toxoplasma gondii antibodies in garbage-fed pigs (67.3% of 199 pigs) was higher than in grain-fed pigs (33.8% of 180 pigs). Antibodies to Trichinella spiralis were found on seven of 31 farms. On five of these farms only a single serum was positive for Trichinella spiralis antibodies. The two remaining farms each had three positive sera (three of ten and three of 25 pigs tested); both of these farms fed garbage to pigs. PMID- 1496805 TI - An association of faecal egg counts and prolactin concentrations in sera of periparturient Angora goats. AB - Faecal egg counts and serum prolactin concentrations in 13 pregnant and five non pregnant Angora goats were monitored over a period of 20 weeks. The mean weekly egg counts of pregnant goats were significantly higher (P less than 0.01) than those of non-pregnant goats. In pregnant goats the mean egg counts in the 6 week post-partum period were significantly higher (P less than 0.01) than those of 6 weeks prepartum. The mean prolactin concentration of pregnant goats during the 6 week post-partum period was significantly higher (P less than 0.01) than that of 6 weeks pre-partum. During the 6 to 3 weeks before parturition, the prolactin values generally remained low (below 100 ng ml-1). The rise in prolactin concentration started between 3 weeks and 1 week before parturition. Only in pregnant goats was there a positive linear regression between prolactin levels and faecal egg counts. PMID- 1496806 TI - Antioxidant system of Litomosoides carinii and Setaria cervi: effect of a macrofilaricidal agent. AB - Filarial parasites, Litomosoides carinii and Setaria cervi, showed great susceptibility to the oxidants generated in vitro by the xanthine/xanthine oxidase system. In order to counteract such injurious effects, both the filariids possessed an active antioxidant enzymes system. Superoxide dismutase, catalase and glutathione peroxidase were detected in appreciable amounts but glutathione reductase and glucose-6-phosphate dehydrogenase in very low quantities. The former three enzymes were also found to be released by the parasites into the ambient medium. The released enzymes may be responsible for scavenging the host generated oxidants present in the immediate surroundings of the parasites and thereby enabling them to live comfortably in the host. This Institute-based antifilarial agent namely Compound 82/437 which is 2,2'-dicarbomethoxylamino-5,5' dibenzimidazolylketone, markedly inhibited catalase and glutathione peroxidase of both L. carinii and S. cervi. The compound, therefore, appears to render the filariids prone to H2O2 toxicity leading to penultimate damage. PMID- 1496807 TI - Restriction enzyme maps for equine adenovirus 1 genome. AB - Physical maps were constructed for the genome of equine adenovirus 1 (EAV1) using the restriction enzymes; DraI, EcoRV, NotI and SfiI. The total size of the EAV1 genome was 34.4 kb estimated by comparison with known DNA standards and the polarity of the fragment order, with respect to the left and right molecular ends, was determined by hybridization with known regions of the human adenovirus 2 (HAV2) genome. PMID- 1496808 TI - Serotype specificity of immunological assays for the capsular polymer of Actinobacillus pleuropneumoniae serotypes 1 and 9. AB - The cross-reactivity of the purified polysaccharides of Actinobacillus pleuropneumoniae serotypes 1 and 9 were examined using a variety of highly sensitive assays, such as radioimmunoassay, latex agglutination, enzyme-linked immunosorbent assay (ELISA), and immunoblotting. In addition, conventional immunodiffusion was included for comparison. Latex agglutination, utilizing affinity-purified IgG to capsule, was also used to serotype whole cells. Agglutination or precipitation tests (radioimmunoassay, latex agglutination, and immunodiffusion) indicated no cross-reactivity between the capsules of serotypes 1 and 9, and no cross-reactivity between whole cells by latex agglutination. Assays that required binding of the capsule to a solid support (ELISA and immunoblotting) did demonstrate cross-reactions between serotypes 1 and 9 capsules, although reactions with the heterologous serotype were weaker than with the homologous serotype. The cross-reactivity could not be attributed solely to nonspecific factors because similar cross-reactivity did not occur with serotype 5 or 7 capsules by any assay. Reactivity of antisera with homologous or heterologous capsule was reduced, but not completely eliminated, by adsorption with washed, live bacteria of the heterologous serotype. Thus, the assay, as well as the antigen or specificity of the antibody reagent used, may influence the results of A. pleuropneumoniae serotyping or serological tests. PMID- 1496809 TI - Occurrence of V-factor (NAD) independent strains of Haemophilus paragallinarum. AB - Strains of Bisgaard taxon 31, isolated from chickens in South Africa suffering from a respiratory disease with clinical symptoms and gross lesions similar to infectious coryza, showed great phenotypical similarities with Haemophilus paragallinarum infection except for NAD requirement, beta-galactosidase activity and maltose fermentation. Deoxyribonucleic acid-deoxyribonucleic acid hybridization confirmed a high level of genetic relatedness (DNA binding value, 89%) with Haemophilus paragallinarum. Guanine + cytosine content and genome size data also support the classification of taxon 31 strains within the species Haemophilus paragallinarum. PMID- 1496810 TI - Factors affecting endotoxin release from the cell surface of avian strains of Pasteurella multocida. AB - Two avian strains of Pasteurella multocida, a vaccine strain and a virulent field isolate, were investigated to determine their propensity to release endotoxin from the cell surface. Both organisms released comparable amounts of endotoxin when plasma complement proteins were present, however the virulent strain did so without the loss of viability that occurred in the vaccine strain. Blocking complement activity decreased the ability of plasma to elicit endotoxin release from the bacteria. When the cells were treated with divalent metal chelators such as trans-1, 2-diaminocyclohexane-N,N,N1,N1-tetraacetic acid (CDTA), more endotoxin was released from the vaccine strain than from the virulent isolate. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) of purified lipopolysaccharide (LPS) from both strains revealed virtually identical patterns. Both had patterns considered typical of rough LPS. Challenge studies in 8 weeks old turkeys showed that the field strain induced endotoxemia of longer duration than the vaccine strain and produced greater mortality. PMID- 1496811 TI - Salmonella cytotonic and cytolytic factors: their detection in Chinese hamster ovary cells and antigenic relatedness. AB - Thirty nine strains of Salmonella belonging to 14 different serotypes were screened for the production of cytotonic and cytolytic factors by assayed Chinese hamster ovary (CHO) cells. The cell-free culture supernatants (CFCS) of 32 isolates caused elongation and increase in size of CHO cells while the CFCSs completely lysed the cells. The cytotonic effect in CHO cells correlated precisely with fluid the CFCSs completely lysed the cells. The cytotonic effect in CHO cells correlated precisely with fluid accumulation in the rabbit ligated ileal assay in that 24 isolates yielded positive results in both assays and 13 were found negative in both. Antiserum to S. typhimurium enterotoxin, but not that to cholera toxin or Shiga toxin, neutralized the cytotonic activity present in the CFCS and reacted with the latter in immunodiffusion and coagglutination tests. The cytolytic factor produced by two strains reacted neither with antiserum to Salmonella enterotoxin nor with that the Shiga toxin. PMID- 1496812 TI - Evaluation of enzyme-linked immunosorbent assay for diagnosis of Clostridium perfringens enterotoxemias. AB - Two double sandwich enzyme-linked immunosorbent assays (ELISA) for Clostridium perfringens beta and epsilon toxins were assessed for routine diagnosis of enterotoxemias on intestinal contents of 151 sheep that died suddenly. Conventional tests (mouse assay and culture of organism) showed that 21 specimens were positive for Clostridium perfringens type C (beta toxin) and 39 were positive for Clostridium perfringens type D (epsilon toxin) enterotoxemias. Comparison of the ELISA results with conventional assays gave sensitivity and specificity rates respectively of 90.5% and 89.2% for beta toxin assay and 97.4% and 94.6% for epsilon toxin assay. With further refinement to improve the performance of the assay for beta toxin these tests could serve as a substitute for conventional tests in the laboratory diagnosis of Clostridium perfringens types B, C and D enterotoxemias. PMID- 1496813 TI - Fungi on Narthecium ossifragum leaves and their possible involvement in alveld disease of Norwegian lambs. AB - Spores of Pithomyces chartarum (Berk. & Curt.) M.B. Ellis were only rarely seen on leaves of Narthecium ossifragum (L.) Hudson collected in summer from five areas in western Norway in which alveld, a photosensitization disease of lambs, is endemic. Cladosporium magnusianum (Jaap) M.B. Ellis was found on all 118 leaf samples collected in the summers of 1990 and 1991. The hypothesis that P. chartarum contributes to the aetiology of alveld could not be supported, but it is possible that C. magnusianum may have a role in the causation of the disease. PMID- 1496814 TI - Bioavailability of ivermectin administered orally to dogs. AB - The bioavailability of three formulations of ivermectin was determined following oral administration to dogs. The average peak plasma level (Cmax) of ivermectin administered in the standard tablet formulation at 6 and 100 micrograms/kg of body weight was 2.97 and 44.31 ng/g, respectively. This suggest dose-dependent pharmacokinetics. Cmax and total ivermectin bioavailability, as assessed from the area under the plasma curve (AUC), were similar between two tablet formulations of ivermectin administered at 100 micrograms/kg. Furthermore, Cmax was similar following administration of radiolabelled ivermectin at 6 micrograms/kg in either a beef-based chewable formulation or in the standard tablet formulation. PMID- 1496815 TI - The pharmacokinetics of a slow-release theophylline preparation in horses after intravenous and oral administration. AB - The pharmacokinetics of a slow-release theophylline formulation was investigated following intravenous and oral administration at 10 mg/kg in horses. A tricompartmental model was selected to describe the intravenous plasma profile. The elimination half-life (t1/2 beta) was 16.91 +/- 0.93 h, the apparent volume of distribution (Vd) was 1.35 +/- 0.18 L/kg and the body clearance (ClB) was 0.061 +/- 0.009 L kg-1 h. After oral administration the half-life of absorption was 1.24 +/- 0.30 h, and the calculated bioavailability was above 100%. The t1/2 beta after oral administration was 18.51 +/- 1.75 h, only a little longer than that after intravenous administration. The slow release formulation did not exhibit any advantage in prolonging the t1/2 beta of theophylline in the horse. PMID- 1496816 TI - The distribution and some pharmacokinetic parameters of ivermectin in pigs. AB - Ivermectin was injected subcutaneously into five pigs at the usual dose rate of 300 micrograms/kg and found to distribute well to all tissues and body fluids which were sampled 24 h post-injection. Ivermectin was detected in the contents and mucus at all levels of the gastrointestinal tract. The drug was excreted in bile, with high concentrations of the drug in the intestines and faeces. High concentrations of ivermectin were measured in skin, ears and ear wax, suggesting that the drug should be effective in the treatment of ectoparasitic infestations, particularly ear mites. The high lipid solubility of the drug may explain the high concentrations found in ear wax and skin. Ivermectin was also detected in the body fluids and tissues of an untreated pig penned with the treated animals. Direct contact appeared to be necessary for transfer of ivermectin from the treated to the untreated pig but coprophagia or urine drinking is a possible explanation. The pharmacokinetics of ivermectin administered subcutaneously at a dose rate of 300 micrograms/kg to six pigs were studied. There was marked individual variation in the pharmacokinetics of ivermectin. In one pig the area under the plasma concentration-time curve was particularly high. This may reflect individual variation in uptake and excretion of the drug. The mean elimination half-life of the drug was 35.2 h, suggesting that the drug is cleared slowly from pigs with drug detectable in plasma for 6-10 days. This persistence should allow a short period of protection before re-infection with parasites. PMID- 1496817 TI - Adherence and colonization by bacterial pathogens in explant cultures of bovine mammary tissue. AB - Explant cultures of bovine mammary tissue taken from virgin heifers were used to examine adherence, colonization and cytopathogenesis of Streptococcus uberis, Streptococcus agalactiae, Streptococcus dysgalactiae, Staphylococcus aureus and Escherichia coli in the putative target tissue. None of the five bacteria was able to adhere to healthy ductular epithelium but all showed a marked tropism for exposed connective tissue. S. aureus and E. coli induced a marked cytopathic effect in ductular epithelium after 6 hours in culture but the bacteria were not in close association with the affected tissue. No evidence could be found to support the hypothesis that adherence to epithelium might be the first stage in the pathogenesis of mastitis caused by these organisms. PMID- 1496818 TI - Passive protection of mice with antiserum to neuraminidase from Pasteurella multocida serotype A:3. AB - Antiserum to a partially purified neuraminidase from Pasteurella multocida, type A:3, was adsorbed with protease-digested P. multocida type 3 lipopolysaccharide (LPS) to remove LPS immunoreactivity. The LPS-adsorbed antineuraminidase caused a 77% reduction in the neuraminidase activity of homologous P. multocida in an in vitro enzyme neutralization test. All 14 mice passively immunized with the adsorbed antineuraminidase were protected against challenge infection with homologous P. multocida in a mouse protection test. Ten out of 14 mice in one group that received antisera containing antibodies to both neuraminidase and LPS were protected. In contrast, only 1 out of 14 mice that were immunized with pre immune serum survived the challenge. These results suggest that antiserum to P. multocida neuraminidase was, at least partly, responsible for the protection observed in this study. Neuraminidase may be one of the immunogenic protective proteins present in aqueous extracts of Pasteurella multocida. PMID- 1496819 TI - Enzymic hydrolysis of nicotinate esters: comparison between plasma and liver catalysis. AB - 1. The enzymic hydrolysis of a wide series of nicotinic acid esters was investigated using human and rat plasma, and purified hog liver carboxylesterase, and compared with previously published data from rat liver microsomes. Esterase activities were always found to obey Michaelis-Menten kinetics. 2. Rat liver microsomal and plasma enzyme velocities were six orders of magnitude smaller than those of purified hog liver carboxylesterase, and three orders smaller than human plasma activities, but the Km values were of the same magnitude. 3. The binding of nicotinate esters to human plasma esterases, and purified hog liver carboxylesterase, appears to depend mainly on hydrophobic and steric factors. PMID- 1496820 TI - The profile of rat liver enzyme induction produced by prochloraz and its major metabolites. AB - 1. The profile of the hepatic mixed-function oxidase system of male rats has been examined following treatment with prochloraz (I) and three of its major metabolites (II, III and IV). 2. The overall induction profile of prochloraz reflected the contribution of the individual metabolites. There was a slight increase of lauric acid hydroxylase, but by far the major induction was seen in the activity of aldrin epoxidase and 7-pentoxyresorufin-O-dealkylase (7- and 14 fold respectively). 3. N-Propyl-N-[2-(2,4,6-trichlorophenoxy)ethyl]urea (II), a primary intermediate in the metabolism of prochloraz, was a phenobarbitone-type inducer, increasing the activity of aldrin epoxidase and 7-pentoxyresorufin-O dealkylase by 120% and 8-fold respectively. 4. The prochloraz metabolites, trichlorophenoxyethanol (III) and trichlorophenoxyacetic acid (IV) were both inducers of the clofibrate type, increasing the activity of lauric acid 12 hydroxylase. 5. The induction profile of prochloraz was of a mixed type, but the predominant characteristics were those of phenobarbitone induction. PMID- 1496821 TI - Bioavailability and toxicological potential of wheat-bound pirimiphos-methyl residues in rats. AB - 1. Wheat-bound residues of 14C-pirimiphos-methyl were fed to albino rats at 1.17 and 7.5 ppm in the diet for 3.5 months. 2. In toxicological tests, 1.17 ppm of bound residues caused an increase of rat alkaline phosphatase activity and blood urea nitrogen, and reduction in lymphocyte and monocyte counts. A dietary level of 7.5 ppm showed a significant decrease in serum cholinesterase activity and in lymphocytes and monocytes, and an increase in alkaline phosphatase activity and of urea nitrogen. 3. Bioavailability data indicate that wheat-bound pirimiphos methyl residues are absorbed by rat. PMID- 1496822 TI - Stereoselective conjugation of a uricosuric diuretic with glutathione by glutathione transferase 3-3. AB - 1. The activity of glutathione (GSH) transferases in rat liver cytosol was inhibited by the (-) enantiomer of a uricosuric diuretic (6,7-dichloro-5[N,N dimethylsulphamoyl]-2,3-dihydrobenzofuran-2-ca rboxylic acid, DBCA) in a concentration-dependent manner. Although the DBCA (+) enantiomer inhibited the activity of liver cytosol GSH transferases, it was less effective. 2. Among four purified GSH transferase isozymes obtained from rat liver cytosol, isozyme 3-3 showed stereoselective interactions with the enantiomers of DBCA. This isozyme most actively and preferentially catalysed the transfer of GSH to DBCA (-) enantiomer. PMID- 1496823 TI - Conjugation of polychlorinated agrochemical sulphoxides and sulphones by glutathione. AB - 1. Pentachlorophenyl methyl sulphoxide and pentachlorophenyl methyl sulphone were found to be substrates for microsomal and cytosolic glutathione-S-transferase of rabbit, monkey, chicken and human liver, covalently immobilized on beaded sepharose. 2. Protein was immobilized with greater than 95% transferase activity, measured by dinitrochlorobenzene. Immobilized rabbit liver microsomal transferase activity was more stable than immobilized cytosolic activity. 3. The sulphoxide moiety was displayed by glutathione in the presence of chicken liver microsomal protein. The sulphone moiety was displayed by glutathione in the formation of a diglutathione under catalysis by rhesus monkey liver cytosolic and microsomal protein. 4. Chlorine was displaced by transferases from all species to form regioisomeric monoglutathiones. 5. Qualitative and quantitative differences were observed in product distributions between species and between microsomal and cytosolic protein. PMID- 1496824 TI - Biotransformation of diethenylbenzenes. III: Identification of metabolites of 1,3 diethenylbenzene in rat. AB - 1. Biotransformation of 1,3-diethenylbenzene (1) in rat gave four major metabolites, namely, 3-ethenylphenylglyoxylic acid (2), 3-ethenylmandelic acid (3), N-acetyl-S-[2-(3-ethenylphenyl)-2-hydroxyethyl]-L-cysteine (4) and N-acetyl S-[1-(3-ethenylphenyl)-2-hydroxyethyl]-L-cysteine (5) were isolated from urine and identified by n.m.r. and mass spectrometry. 2. Four minor metabolites, 3 ethenylbenzoic acid (6), 3-ethenylphenylacetic acid (7), 3-ethenylbenzoylglycine (8) and 2-(3-ethenylphenyl)ethanol (9) were identified by g.l.c.-mass spectrometric analysis of urine extract derivatized in two different ways. 3. All identified metabolites are derived from 3-ethenylphenyloxirane (10), a reactive metabolic intermediate. No product of any metabolic transformation of second ethenyl group has been identified. However, several minor unidentified metabolites were detected by g.l.c.-mass spectrometry. 4. Total thioether excretion in 24 h urine after a single i.p. dose of 1 amounted to 28.3 +/- 3.5 dose (mean +/- SD). No significant differences in the thioether fraction were observed in the dose range 100-300 mg/kg. 5. Thioether metabolites consisted mainly of mercapturic acids 4 and 5. The ratio of metabolites 5 to 4 was 62:38. Each mercapturic acid consisted of two diastereomers. Their ratio, as determined by quantitative 13C-n.m.r. measurement was 95:5 and 79:21 for mercapturic acids 4 and 5, respectively. PMID- 1496825 TI - Metabolism of coumarin by rat, gerbil and human liver microsomes. AB - 1. o-Hydroxyphenylacetaldehyde was the major metabolite of coumarin (1 mM) in rat, gerbil and human liver microsomes. 2. Treatment of rats with phenobarbitone (PB) or beta-naphthoflavone increased the o-hydroxyphenylacetaldehyde formed. 3 Hydroxycoumarin was the other main metabolite produced by rat liver microsomes. 3. Liver microsomal metabolism of coumarin in gerbil was extensive with 3-, 5-, 6 , 7- and 8-hydroxycoumarins, and 3,7- and 6,7-dihydroxycoumarins produced, in addition to o-hydroxyphenylacetaldehyde. The profile of the hydroxy metabolites was altered by in vivo treatment of gerbils with cytochrome P-450 inducers, but there was no increase of coumarin metabolism. 4. Coumarin was metabolized by human liver microsomes to o-hydroxyphenylacetaldehyde, 7-hydroxycoumarin, 3 hydroxycoumarin, and trace amounts of 5-, 6- and 8-hydroxycoumarins. 5. At low substrate concentrations (0-10 microM) hepatic microsomal metabolism of coumarin in gerbil resembled that in man, with 7-hydroxycoumarin being a major metabolite. However, the production of o-hydroxyphenylacetaldehyde was greater in gerbil than human liver microsomes. 6. At higher substrate concentrations (1 mM) metabolism of coumarin by liver microsomes from PB-treated gerbils most closely resembled that by human liver microsomes. 7. The gerbil would appear to be a more appropriate animal model than rat for studies to assess the toxicological hazard of coumarin for man. PMID- 1496826 TI - The pharmacokinetics of propofol in laboratory animals. AB - 1. The pharmacokinetics of propofol in an emulsion formulation ('Diprivan') have been studied after single bolus doses to rats, dogs, rabbits and pigs, and after single and multiple infusions to dogs. Venous blood propofol concentrations were determined by h.p.l.c. with u.v. or fluorescence detection. Curve fitting was performed using ELSFIT. 2. The distribution of propofol in blood and its plasma protein binding have been studied in rat, dog, rabbit and man. Protein binding was high (96-98%), and in most species propofol showed appreciable association with the formed elements of blood. 3. Where an adequate sampling period was employed the pharmacokinetics of propofol were best described by a three compartment open 'mammillary' model. Propofol was distributed into a large initial volume (1-21/kg) and extensively redistributed (Vss = 2-10 x body weight) in all species. Clearance of propofol by all species was rapid, ranging from about 30-80 ml/kg per min in rats, dogs and pigs to about 340 ml/kg per min in rabbits. PMID- 1496827 TI - Plasma and urinary concentrations of methamphetamine after oral administration of famprofazone to man. AB - 1. To obtain further evidence for the metabolic formation of methamphetamine from famprofazone in man, concentrations of methamphetamine in plasma, as well as in urine, were measured by g.l.c. In addition, intact famprofazone and famprofazone N-oxide were analysed in the urine. 2. Methamphetamine appeared in plasma 1 h after a single 100 mg dose of the drug to two male subjects, and the concentration maintained between 24 and 44 ng/ml over 2-12 h, declining to 10 ng/ml and an undetectable level respectively after 24 h. 3. Total urinary excretion of methamphetamine over 72 h was 1.9 mg for a 25 mg dose and 2.2 mg for a 50 mg dose. After a 100 mg dose, 4.6 mg of methamphetamine was excreted over 36 h. Neither intact famprofazone nor famprofazone N-oxide were detected when the urine samples after the 100 mg dose were examined. 4. The results provide further evidence that methamphetamine is a bona fide human metabolite of famprofazone and suggest that at least 20% dose may be broken down via the pathways leading to the formation of methamphetamine. This could have significant clinical implications as the result of pharmacological activity of this metabolite. PMID- 1496828 TI - Hepatic lipid peroxidation and trace elements--nutritional status in streptozotocin-induced diabetic rats. AB - The aim of this experiment was to study the interrelationships between nutritional status of chosen trace elements (Cu, Zn, Fe) and hepatic lipid peroxidation in streptozotocin-induced diabetic rats. Both copper accumulation and disruption of iron storage were observed in livers of diabetic rats. MDA 0' (baseline) and MDA 30' (produced) levels measured in the liver were negatively correlated with blood glucose levels. MDA 30' levels correlated positively with iron concentration in the liver. It is supposed that the hormonal lability during experimental diabetes caused changes in metabolism of trace elements, and subsequently influenced the rate of lipid peroxidation. PMID- 1496829 TI - [Vitamins during high dose chemo- and radiotherapy]. AB - Plasma from 22 patients was examined for alpha- and gamma-tocopherol (vitamin E), the carotenoids beta-carotene (provitamin A) and lycopene, retinol (vitamin A), and ascorbic acid (vitamin C) before, during and after conditioning chemotherapy for bone marrow transplantation, 18 of these received total body irradiation as well. In addition, alpha-tocopherol in red blood cell membranes was measured. Retinol and ascorbic acid have been applied in multiple of the recommended doses (Deutsche Gesellschaft fur Ernahrung and Recommended Dietary Allowance, respectively). The chosen doses were sufficient to maintain the initial plasma concentrations of these vitamins. However, alpha-tocopherol (in RDA doses) and beta-carotene (no RDA established) concentrations deteriorated after the conditioning therapy (20 and 50% loss, respectively). The loss of these lipid soluble antioxidants has been considered to result from lipid peroxidation. On the basis of the presented results we propose intervention studies to investigate the effect of high dose antioxidant administration on the toxicity (mainly of liver and lung) of intensive antineoplastic therapy protocols. PMID- 1496830 TI - Retrospective approach to explain growth retardation and urolithiasis in a child with long-term nutritional acid loading. AB - An infant with phenylketonuria unintentionally received a highly acidic low phenylalanine diet for 29 months. Temporary growth retardation and urolithiasis were observed, probably as direct effects of chronic acid loading. Caries at the age of 6 years may be a late consequence. This case report shows that chronic dietary acid load may cause serious side effects. PMID- 1496831 TI - The fatty acid composition of subcutaneous fat in German adults. AB - The fatty acid (FA) composition of subcutaneous fat (SCF) was analyzed in 47 German adults. No influences of sex or age on the FA status of the probands could be detected. SCF consisted mainly of monoenoic fatty acids. Linoleic acid was the major polyunsaturated fatty acid. Linoleic acid metabolites were found in small quantities only. In comparison to the results of studies in the USA and the Netherlands the FA composition of SCF in German probands was characterized by lower levels of linoleic acid and higher contents of palmitic acid. The trans-FA content was similar to that in Dutch women, but lower than in American male probands. However, in evaluating the differences in the FA composition of SCF in different countries, it has to be noted that there are wide ranges in the proportions of the major FA in all populations studied. PMID- 1496832 TI - Mn-content of total parenteral and enteral nutrition. AB - Manganese has been proven to be an essential trace element in animals since 1931. Today, it is known that manganese deficiency results in a wide variety of structural and physiological defects in animals. For humans, the safe and adequate range of intakes for manganese by enteral nutrition is 2.0 to 5 mg per day; for parenteral nutrition a range of 0.15 to 0.8 mg per day is proposed. The manganese content of components of enteral nutrition (EN) and total parenteral nutrition (TPN) solutions is determined using electrothermal atomic absorption spectrometry. Comparison is made between calculated and measured values. The manganese present in supplementary nutrition and flavor stuffs is also measured. The intake of manganese by EN is calculated based on the daily administration, and is found to vary from 192 to 7373 micrograms per day. In prepared TPN solutions, the manganese contribution of all components before adding the Oligo Complex is found to be less than 0.2% of the total manganese content. After addition of the Oligo Complex mixture, a mean daily intake of 5.02 +/- 0.16 mg per day is found. PMID- 1496833 TI - Quantitation of carbohydrate sweeteners and organic acids in human oral fluid using HPLC analysis. AB - A sensitive high performance liquid chromatography (HPLC) assay was developed for the qualitative and quantitative determination of carbohydrate sweeteners and organic acids in oral fluid. To separate these compounds, an ion-moderated partition resin HPLC column (Aminex HPX-87H) was used. All components of the HPLC system were interconnected using stainless steel capillary tubing. Isocratic elution with 0.01N sulfuric acid provided the profile of both compound classes. The compounds were detected using a refractive index detector. The method employed computerized data collection and integration (Omega-2 system) with a detection sensitivity of 0.1 micrograms compound per HPLC assay (80 microliters). This method is useful in caries research, because it detects minute amounts of sugars and organic acids in oral fluid during clearance studies of various foods in the mouth. PMID- 1496835 TI - [Developmental trends in the malpractice process. I: Are physicians seeking refuge in defense medicine?]. PMID- 1496834 TI - [The determination of free and bound methylated nucleobases in food]. AB - The following method was developed for the qualitative and quantitative determination of methylated purine and pyrimidine bases in food; some RNA-rich food was also investigated. The bases were liberated from nucleic acids, nucleotides, and nucleosides by acid hydrolysis with trifluoroacetic and formic acid (1/1, V/V) at 240 degrees C in a pressure-digestion system. Purification and fractionation of hydrolysates were achieved by sorbent extraction with an RP 18 column and a cation exchange column. The major and methylated nucleobases were determined by ion-exchange chromatography and reversed-phase-HPLC. PMID- 1496836 TI - [Extracorporeal shockwave lithotripsy of gallstones. Retrospective view and perspectives]. AB - Extracorporeal shock-wave lithotripsy (ESWL) is a non-invasive technique in gallstone management, which has been in clinical use since many years now. Exact patient selection provides considerable stone-free rates within a year. Side effects and complications are rare. The stone-recurrence rate is about 15% after two years, and thus lower compared to that after oral dissolution therapy alone. Until now, there is no reasonable medical therapy to prevent stone recurrence. Furthermore, ESWL is a suitable therapy for retained common bile duct stones. Although laparoscopic cholecystectomy has become established as a new, minimally invasive surgical method, ESWL will continue to be a successful technique for the treatment of thoroughly selected gallstone patients, who are looking for a non invasive way to get rid of their biliary pain, but not of their gall bladder. PMID- 1496837 TI - [Densitometry determination of coronary flow rates using digital subtraction angiography (DSA). Methods, multiple examinations and interobserver comparison]. AB - In invasive diagnostics of coronary heart disease (CHD), three each DSA examinations of the left coronary artery were performed at 2-minute intervals in ten patients subsequent to conventional examination by means of a left-side cardiac catheter and coronary angiography. While placing the patient in left anterior oblique (60 degrees) position, 6 ml each of ionic contrast medium were injected mechanically with a flow of 4 ml/sec at a pacemaker-induced heart rate of 100/min. Examinations were performed according to a standard mode and were evaluated via the image analysing computer APU of the Philips DVI-DSA system. The purpose of this approach was to analyse the examination conditions and a new improved evaluation algorithm in respect of stability, feasibility and sensitivity. 17 series were evaluated by two examiners who were independent of each other. The interobserver differences obtained were between 5% at the time of maximum density (Tmax) and 25% with exponential downward slope of the curve (lambda), with reference to the median value in each case. Scatter of the individual examinations around the median value of all the three DSA runs is 11 to 17% with the exception of lambda. A significant rise can be proven in the RCX region for the curve slope rise parameters "slope" and "RFL2". We interpret this as a genuine 1.2 to 1.3 fold regional flow increase due to the residual effect of the contrast medium. At the same time, this can be interpreted as an indicator for the good sensitivity of the method.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1496838 TI - [The effect of health resort therapy on cardio-regulation following heart transplantation with special reference to CO2 balneotherapy]. AB - It is being reported about the influence of a CO2-bathing series with 12 patients after heart-transplantation in connection with a light-motion therapy on blood pressure and haemodynamics. The comparative group was a group of 12 heart transplantation patients of the same age without cure during the comparative time. It was shown that the balneotherapy after HTPL has positive effect on the development of the systolic blood pressure under rest and exercise. The peripheric microcirculation (musculus tibialis anterior) improved significantly. The left ventricular ejections fraction (LVEF) kept without change. Generally, the balneotherapy is well tolerated by heart-transplantation patients. There is no danger of a cardiac overcharge of the left ventricle. PMID- 1496840 TI - [Superoxide dismutase activity of Ginkgo biloba extract]. AB - The Ginkgo biloba extract is obtained from green leaves of the Ginkgo biloba tree. Preparations with this active substance are among others used for the treatment of disturbances of the cerebral function and arteriosclerotic diseases. In in-vitro and in-vivo studies antagonistic effects of radical scavenger and PAF (platelet activating factor) were described. In this study a concentration depending superoxide dismutase activity of the Ginkgo biloba extract rokan liquid could be made evident. PMID- 1496839 TI - [Effect of desmopressin (DDAVP) on blood platelet parameters in vivo and in vitro]. AB - Coagulation assays including DDAVP test were carried out in 15 patients preoperatively, evaluating several parameters of platelets during the assays. After DDAVP infusion we observed a decreased spontaneous aggregation in whole blood, an increased retention to glass beads, and in a number of cases a raised in vitro-formation of thromboxane. By application of DDAVP, a significant enhancement of spontaneous aggregation in whole blood and left shift to smaller volumes of the platelet volume distribution were demonstrated in vitro. It is concluded that DDAVP has an indirect inducing effect on aggregation, probably by release of ADP from red blood cells. PMID- 1496841 TI - [Importance of left ventricular function for active early ambulation following acute myocardial infarct]. AB - On the 4th postmyocardial infarction day a risk group determination among n = 80 patients was undergone on the base of LDH-isoenzyme-monitoring. The active early mobilization was carried out following corresponding risk groups: less risk (38%) until the 14th, middle risk (23%) until the 21st and high risk (38%) until the 28th postmyocardial infarction day or longer. The average period of hospitalization was 21.1 day. The exercise load test was done successful in 97% by patients with low risk and in 40% by patients with high risk. The ejection fraction was 51.3% for patients with low risk and 38.5% (p less than 0.01) for patients with high risk. The exercise test at discharge is usefull for check of the risk from the acute phase and for the determination of high-risk patients for physical conditioning. PMID- 1496842 TI - [In memory of Hermann Jastrowitz (1882-1943)]. AB - The 50th anniversary of the infamous "Wannsee Conference" that was held on 20 January 1942 at Berlin prompts us to recall the memory of the life and achievements of physicians who were the victims of the measures that had been decreed during that conference-physicians who made medical history both during their lifetime and by the fate they endured. One of these was the Jewish physician Hermann Jastrowitz, whose meritorious achievements for the benefit of the Outpatient Division and Hospital of the Department of Medicine of the University of Halle have been practically completely documented and reconstructed from university and other records. PMID- 1496843 TI - [Combined monitoring of labor: maternal and neonatal results]. AB - The purpose of this study was to prove, whether intrapartum fetal monitoring by cardiotocography and fetal blood analysis brings advantages for mother and child. The data of 10,234 patients, delivered in 5 different hospitals in 1988 and 1989, were analyzed by a computer. The results show that nonpermanent in comparison to permanent monitoring lead to a significant increase in cesarean section rate, neonatal morbidity and perinatal mortality. Furthermore we found a negative correlation between cesarean section rate and frequency of fetal blood analysis (r = -0.54). The use of fetal blood analysis in cases with pathological fetal heart patterns lead to a significant reduction in cesarean section rate, neonatal morbidity and perinatal mortality. In summary the study shows that a combined intrapartum monitoring improve the results. PMID- 1496844 TI - [Imaging of premature uterine contraction in vaginal sonography]. AB - A collective of 60 patients with clinical diagnosed contractions was vaginosonographically examined. During the ultrasound examination preterm labour was seen in 42 patients. In a control group (n = 50) preterm contractions were not detectable. The average time of the contractions was 88 seconds in the primipara group and 90 seconds in the multipara group and showed no statistical significance. In the group of the primipara a shortening of the cervical length of 17 (+/- 6) mm, in the multipara group 15 (+/- 5) mm was seen under contractions, furthermore a thickening of 8 +/- 4 mm respectively 10 +/- 5 mm. The internal os of the primipara opened 11 +/- 6 mm, of the multipara group 13 +/ 6 mm. The highest incidence of uterine contractions was found in the 32nd week. The paired students t-test showed a significance of p less than 0.001 for the cervical length, thickness and internal os and for the thinning of the dorsal uterine wall, subdividing the parity did not show statistical significance. The vaginosonography is able to help detecting preterm labour. PMID- 1496845 TI - [Increased spontaneous uterine motility with serotonin]. AB - The influence of serotonine, a vasoactive neurotransmitter, on the spontaneous motility of uterine strips was investigated. A highly significant (p less than 0.001) increase of uterine activity was observed when serotonine 10(-6) M was added to the perfusing medium. PMID- 1496846 TI - [The value of adjuvant ampicillin therapy in idiopathic premature labor]. AB - Evidence suggests that subclinical intrauterine infection may play an etiologic role in preterm labour. To test the hypothesis, that treatment with antibiotics might delay delivery, we retrospectively have investigated 104 women in idiopathic preterm labour who were given ampicillin additional to tocolysis and 90 comparable women without antibiotic treatment. There were no significant differences between the two groups in regard to prolongation of gestation, gestational age at delivery, fetal weight, fetal well-being or connatal infections. Adjuvant ampicillin treatment of women in idiopathic premature labour without other signs or indicators of subclinical intrauterine infection seems not beneficial. PMID- 1496847 TI - [Hypotonic symptoms and pregnancy]. AB - To our knowledge there is no study that answers the question, whether low blood pressure itself or the fall of blood pressure during standing have a negative effect on pregnant women. These patients suffer from signs of reduced central and/or peripheral blood flow like fatigue, headache, cold extremities, paresthesia, flickering, black outs and dizziness. In addition, it is of interest whether frequency, occurrence and intensity of these hypotensive symptoms alter during pregnancy. In a longitudinal study 12 hypotensive pregnant women were compared with 13 normotensive and later on in a randomized study 102 clinical healthy pregnant women were tested with a modified orthostatic test over defined time periods during pregnancy. Blood pressure and heart rate were registered in one minute intervals over 30 minute period with an automatic Dinamap measuring device. This period was subdivided in a 10 minutes lying period, 10 minutes standing period followed by a 10 minutes lying period. In addition, the pregnant women were asked about frequency, occurrence and intensity of typical hypotensive symptoms. The frequency of subjective symptoms were related to low blood pressure (p less than 0.001) but not to the fall in blood pressure during standing. The occurrence of different hypotensive symptoms (p less than 0.05) and their intensity (p less than 0.01) were most often in early pregnancy and decreased until term. We conclude that the subjective symptoms were twice as much during early pregnancy than during late pregnancy and were more often in patients with low blood pressure. Furthermore, fatigue, headache and cold extremities occur frequently during pregnancy.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1496849 TI - [Inpatient psychotherapy of hyperemesis gravidarum--a case report]. AB - Although now there is no doubt about the role of psychosocial factors in hyperemesis gravidarum, remarkably little literature can be found on the subject of psychotherapy and hyperemesis. This may be due to the decreasing number of severe cases, light cases generally do not require treatment. In the past, mostly hypnosis and several different types of supportive psychotherapy were propagated. We are reporting about the trial attempt of treating a patient with hyperemesis gravidarum with in-patient psychotherapy on an internal medicine-psychosomatics ward in tight cooperation with the referring gynaecological clinic. We suggest in patient psychotherapy as one possibility of treating protracted vomiting in pregnancy. PMID- 1496848 TI - [Internal urinary diversion in complicated pregnancy-induced hydronephrosis]. AB - In 14 women with sympthomatic hydronephrosis of pregnancy (calix diameter 1-2.6 cm) an internal urinary drainage was carried out during the second half of pregnancy. Retrograde stenting was performed following cystoscopy in all cases. Follow up examinations were taken weekly for the first two weeks and further on biweekly. Primary stenting was possible in 12 out of 14 cases and in 2 patients dilatation of the ureteral orifice was necessary. 11 out of 14 patients suffered from complications consisting of severe dysuria (9x), urinary tract infection (7x), persisting lumbar pain plus catheter lumen obstruction (6x each) as well as catheter dislocation (3x). Long term follow up showed that urinary tract obstruction was relieved by stenting in only 6 out of 14 patients. Sufficient urinary drainage by so called double-J-ureteral stents was achieved in less than half of the cases. Moreover, there was a complication rate of more than 75%. Taking these results into consideration, internal drainage of complicated pregnancy hydronephrosis needs careful evaluation. PMID- 1496850 TI - [Emergency Cesarean section--basic data]. AB - Performing a computerized multicenter-study of 66 clinics in the state of North Rhine-Westfalia concerning the management of emergency caesarean-section (ECS), the resulting basic data were calculated as follows: In 207 cases of ECS studied, the time period needed from the decision for operation on to the beginning of surgery (DFOS) is on the average 20.4 +/- 12.3 minutes (Median 17 min., 90th Percentile 37 min.). The mere duration of surgery until delivery of the baby averaged to 4.4 +/- 2.1 min. (Median 4.0 min., 90th Percentile 7 min.). In an emergency case, on the average 24.8 +/- 12.9 minutes (Median 22 min., 90th Centile 43 min.) pass by from the decision for the operation until delivery. The median actual pH-value in umbilical artery blood of these neonates was 7.169 +/- 0.160 (N = 168). 25.0% of these neonates had pH-values below 7.1, 16.0% below 7.0 and 3.0% below 6.900. 20.1% of these babies had an Apgar-score of less than or equal to 3 after 1 min., 4 newborns received a score of 0, but recovered, whereas 4 other demised. The unpurified perinatal mortality amounted to 53.1/1000, the purified one to 48.3/1000. From these data we conclude for the time being, that 1. efforts have to be made to shorten the time factors (especially the first one (DFOS)), although there is still no evidence, that severe neonatal acidosis is significantly associated with undue long time factors in ECS; 2. further thorough analysis is need to evaluate the medical profile and the organizational background of these highest risk-deliveries. PMID- 1496851 TI - [Prostacyclin in hypertension]. AB - Prostacyclin (PGI2) is known to cause vasorelaxation and inhibit platelet aggregation by receptor-mediated mechanisms. While cyclic (c) AMP is known to act as a second messenger for inhibition of platelet aggregation, vasorelaxation by hyperpolarization has been described only recently and may provide an explanation, in addition to stimulation of cAMP for the PGI2 mechanism of action on blood vessels. When PGI2 is infused into healthy volunteers it reduces blood pressure only at infusion rates that also cause significant side-effects, primarily, nausea, emesis, flushing, diaphoresis, and restlessness. In hypertensive patients blood-pressure responses are complex and are influenced to some extent by renin secretion. PGI2 stimulates renin secretion by a direct effect on the juxtaglomerular apparatus, and it also has an indirect effect by activating the sympathetic nervous system. Thus, it is useless as an antihypertensive agent even apart from its debilitating side-effects. Vascular PGI2 is synthesized endogenously by both the endothelial cells and the muscularis of arteries. While the endothelial cells undoubtedly synthesize large amounts of PGI2, the muscularis comprises a much larger tissue mass so that the overall synthesis is about equally distributed between the endothelial and muscle cells. In patients with pregnancy-induced hypertension and some patients with essential hypertension endogenous synthesis of PGI2 has been evaluated by measuring 2,3 dinor-6-keto-PGF1 alpha and has proved to be greatly reduced. Some drugs (thiazides, propranolol) have been shown to stimulate PGI2 synthesis, and inhibition of cyclooxygenase has been shown to reduce their antihypertensive effects. The effects of low- and high-dose aspirin on prostacyclin and thromboxane synthesis are discussed.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1496853 TI - [Increase in creatine kinase and its MM isoforms after successful and uncomplicated coronary angioplasty]. AB - During successful and uncomplicated angioplasty (PTCA), we studied the effect of a short lasting myocardial ischemia on plasma creatine kinase, creatine kinase MB activity, and creatine kinase MM-isoforms (MM1, MM2, MM3) in 23 patients. Eleven patients, in whom diagnostic coronary angiography was performed, served as the control group. Blood was sampled after PTCA and every 2 h for the next 12 h, and after 24 h. CK- and CK-MB activities were determined enzymatically, the MM isoforms by isoelectric focussing. After PTCA total CK and CK-MM3 increased significantly from 23 +/- 10 to 40 +/- 31 U/I (p less than 0.01) and from 18 +/- 5 to 32 +/- 10% (p less than 0.0005), respectively. The ratio MM3:MM1 also increased significantly from 0.4 +/- 0.1 to 1.2 +/- 0.7 (p less than 0.0005). Enzyme maxima for CK-MM3 and the ratio MM3:MM1 were reached 6 h after PTCA, for total CK 10 h after PTCA. This increase was independent of changes in the ECG, of symptoms during PTCA, as well as of the number and duration of balloon inflations. In the control group no changes in enzyme activity were found. Thus, after uncomplicated PTCA a significant increase of total CK and CK-MM-isoforms can be found, which may be due to the short-lasting myocardial ischemia following coronary occlusion. PMID- 1496852 TI - [Correlation between risk profile and severity and age at manifestation of coronary heart disease--findings in 3,715 patients]. AB - In 3715 survivors (pts) of an acute myocardial infarction (3343 males and 372 females), of ages between 20 and 80 years (mean 52.9 +/- 7.7 years), lipid metabolism, amount of cigarette-smoking, severity of coronary artery disease (CHD) by selective coronary arteriography, and age at first manifestation of CHD documented by myocardial infarction were investigated. In contrast to normals, there is a significant reduction of disorders of lipid-metabolism with increasing age. The rate of cigarette-smoking is lower in the elderly. Females are affected by MI 3.6 to 5.3 years later than are males. There was a strong correlation between the degree of lipid-disorders and the severity of CHD, whereas the lipid disturbances were mostly marked in the younger pts. Dependent on the degree of the underlying lipid-disorder, CHD strikes pts at a younger age, whereby the Chol/HDL-Chol-ratio is most sensitive. In a similar manner, cigarette-smoking transfers the manifestation-date of CHD "dose-dependent" to a younger age. Smokers with a daily consumption of more than 40 cigarettes are 9.2 years younger at the time of first myocardial infarction than are non-smokers. In older pts the influence of lipid-disorders and smoking becomes smaller, compared with the risk factor "age", but it is also significant. The proven correlation between the risk profile and the age at first myocardial event stresses the need for preventive and educative strategies. PMID- 1496854 TI - [Initial studies of the possibility of selective ablation of arteriosclerotic vascular changes using laser-induced shock waves]. AB - We studied the effect of laser-induced shock waves in 94 arterial segments from freshly obtained autopsy material. In analogy to the well-established method of shock-wave based lithotripsy, the new principle of our treatment depends on an indirect interaction of the laser energy with the arterial wall via laser-induced mechanical shock waves (angiotripsy). We used a Nd:YAG laser, 1064 nm, 8-20 ns pulse-length to create shock waves that effected smooth craters in arteriosclerotically affected arteries. The histological examination found no thermal damage. Shock waves applied to the healthy and normal arterial wall only resulted in focal intimal ablation and in a minor loosening of the medial structures. The examination of the irrigation solution by means of a laser guided, high-resolution analysis of the particles revealed that, in 97%, the particles created by our shock wave angiotripsy showed a diameter of less than 5 mm and an area of less than 25 mm2. Based on these first in vitro results, it seems possible to ablate arteriosclerotically affected tissue without significant damage to normal wall segments. Further in vitro and in vivo studies are required to evaluate the clinical implications of this new therapeutic approach. PMID- 1496855 TI - [The effect of Belzer and Bretschneider cardioplegia solutions on myocardial energy metabolism. A study with 31phosphorus magnetic resonance spectroscopy in an animal model]. AB - The aim of our study was to test the effectiveness of two cardioplegic solutions and to compare the level of high energy phosphates in the myocardium. We investigated 18 hearts of pigs (obtained from a slaughter-house) with 31phosphorusmagnetic resonance spectroscopy (31P-MRS) In this experiment coronary arteries were cannulated and reperfused with arterial blood to revitalize the heart. When the heart showed regular pulsations coronary arteries were perfused for cardioplegia either with the UW-(Belzer-) or with the HTK-(Bretschneider )solution. For 31P-MRS, a magnet with a magnetic flux density of 4.7 Tesla (T) was available. Relative concentrations from phosphocreatine (PCr/beta-ATP; high energy phosphate) and inorganic phosphate (Pi/MDP; MDP = methylendiphosphonat = reference solution; low-energy phosphate) were calculated from the spectra. As a result of this study, the HTK-solution showed a significantly higher PCr/beta-ATP ratio in the myocardium than the UW-solution during the examination time of 3 h. After plegia of the myocardial area from the right coronary artery PCr/beta-ATP ratios were lower in comparison with the left coronary artery distribution area. The calculation of Pi/MDP-ratios proved that Pi was higher in the myocardium after application of the UW-solution compared to HTK-solution. The kinetics of the metabolites showed an approximately linear and parallel decrease of PCr/beta ATP-ratios after cardioplegia with both solutions during the examination time. PMID- 1496856 TI - The 16th International Conference on Yeast Genetics and Molecular Biology. Vienna, Austria, August 15-21, 1992. Abstracts. PMID- 1496857 TI - The International Community of Yeast Genetics and Molecular Biology. PMID- 1496858 TI - Analysis of acesulfame-K, saccharin and preservatives in beverages and jams by HPLC. AB - A method is described that permits the simultaneous determination of acesulfame K, saccharin and benzoic and sorbic acid in beverages and jams. The results of the HPLC analysis, using an RP-C 18 separation system with UV detection at 227 nm are reported. PMID- 1496859 TI - [Sensitive and selective HPLC methods with prechromatographic derivatization for the determination of cyclamate in foods]. AB - A sensitive and selective high pressure liquid chromatography (HPLC) procedure for the determination of sodium cyclamate in juices and preserves is presented. The method depends on the oxidation of cyclamate to cyclohexylamine, which then is converted prechromatographically into a fluorescent derivative. It is analyzed by HPLC on a C18:reversed-phase column and determined with fluorescence detection (excitation at 350 nm, emission at 440-650 nm). The detection limit of sodium cyclamate was 0.5-5 mg/kg, depending on the nature and dilution of the samples. The relative standard deviations thus obtained were +/- 1.0 to +/- 2.6%. The average recovery was 90%. PMID- 1496860 TI - Equilibrium kinetics of D-glucose to D-fructose isomerization catalyzed by glucose isomerase enzyme from Streptomyces phaeochromogenus. AB - The time course of the glucose isomerization was investigated. At equilibrium the fructose content in the reaction mixture was 52% of the initial glucose concentration. The equilibrium constants K1 and K-1 for the isomerization reaction were determined at 60 degrees C. Two graphical plots were developed to reduce the problems of determining the individual constant. These plot methods for chemical reaction kinetics were applied with equal validity to the kinetics of glucose isomerization process. PMID- 1496861 TI - Histochemical and morphometric studies of peripheral muscle in bovine progressive degenerative myeloencephalopathy of brown Swiss cattle. AB - Histochemical and morphometric analysis of selected skeletal muscles was performed on 14 pure bred, Brown Swiss cattle. Nine cattle were clinically affected with bovine progressive degenerative myeloencephalopathy (BPDME) while five served as controls. Statistically significant trend differences were not observed for the parameters of mean cross sectional area, and mean fiber type percentages for types, I, IIA, and IIB fibers between affected and control test groups. In general, patterns of hypertrophy or atrophy, fiber type grouping, fiber type predominance, or fiber cross sectional profile alteration were not observed in the muscles examined from affected cattle. The findings suggest that BPDME, or weaver syndrome, is not a muscular dystrophy and that muscle pathology is not a primary part of the syndrome nor would muscle pathology be expected to contribute significantly to the clinical signs of the disease. PMID- 1496862 TI - [The frequency of neoplasms in dogs dissected in Berlin]. AB - A retrospective study of relative frequencies and relative risks of cancer of 7,169 dogs which were necropsied between 1981 and 1990 at the Institute of Veterinary Pathology of the FU Berlin was performed. In the sample cancer as cause of death accounted for 24.08% of all necropsied dogs. The mean age of dogs with cancer was 10.2 years while dogs without cancer died at a mean age of 5.3 years. Relative risks of cancer were 1.16 for females and 0.86 for males. Cancer was found in 41.9% of all necropsied boxers, which showed the highest relative risk (1.81) of all breeds. Lymphatic and hematopoietic organs and mammary glands were the most frequent site for tumors. Altogether it could be shown that the most frequent tumors were of epithelial origin (43.91%). PMID- 1496863 TI - Preliminary experience with the diagnostic value of the canine corticosteroid induced alkaline phosphatase isoenzyme in hypercorticism and diabetes mellitus. AB - The present study communicates the interim experience with the diagnostic value of the canine corticosteroid-induced alkaline phosphatase isoenzyme (CIAP), qualitatively assessed by agarose gel electrophoresis, for the diagnosis of Hypercorticism (prolonged exposure to increased concentrations of exogenous or endogenous corticosteroids) and Diabetes mellitus. A total of 106 canine serum samples with a total alkaline phosphatase activity greater than 2.90 mu kat/l were included. CIAP was identified in 28 out of 29 cases of Hypercorticism, in 7 out of 9 cases of Diabetes mellitus, and in 33 out of 68 cases of various other diseases. Sensitivity and specificity with respect to Hypercorticism were 0.97 and 0.48, respectively, while for Diabetes mellitus sensitivity and specificity were 0.78 and 0.37. From this, the positive and the negative predictive values were calculated using standard formulas. The main conclusion may be summarized as follows: In the dog, only the negative finding of CIAP seems to be of diagnostic value in ruling out Hypercorticism as a cause for an increased total alkaline phosphatase activity. PMID- 1496864 TI - The effect of regional nerve blocks on the lameness caused by collagenase induced tendonitis in the midmetacarpal region of the horse: a study using gait analysis, and ultrasonography to determine tendon healing. AB - The influence of regional nerve blocks on lameness resulting from tendon injury was studied in six horses. Tendonitis was induced in the midmetacarpal region of the Superficial Digital Flexor Tendon (SDF), Deep Digital Flexor Tendon (DDF) and the Suspensory Ligament (SL) through collagenase injections. The results were evaluated through sequential clinical examinations, ultrasonographic imaging and kinetic gait analysis (force plate) during a period of 144 days post injury and subsequently compared with gross and microscopic findings. The lameness corresponding to the SDF and DDF tendon lesions was completely abolished by a high palmar nerve block. The SL desmitis was partly abolished by high palmar nerve block and completely blocked with an additional ulnar nerve block. The ultrasonic evaluations showed the lesions, expanding until approximately 30 days post injection (p.i.) and subsequently decreasing. The texture of the lesion also improved markedly after 30 days p.i. The post-mortem macro- and microscopic evaluation revealed still considerable abnormalities at 145 days p.i. At that time the tendon lesions were no longer detectable ultrasonographically. PMID- 1496865 TI - Instrumentation for simultaneous recording of compound muscle action potentials and related force in the dog. AB - An examination apparatus for the study of both compound muscle action potentials and related isometric force of the target muscle after supramaximum electrical stimulation of the respective nerve is described. Force transducers were used to record forces from the forelimb paws and the jaws of the dog. The unit is suitable for the clinical examination of neuromuscular transmission disturbances and for testing the effect of relaxant agents. PMID- 1496866 TI - Testicular ultrastructure of Zebu bulls in Costa Rica. AB - The testicular ultrastructure of sexually mature Zebu (Bos indicus) bulls from Costa Rica was studied in relation to their classification based on andrological examinations undertaken in the field. Based on the testicular consistency at palpation, each bull was assigned to one of three groups, ranging from normal (Group A) to markedly reduced testicular consistency (Group C). The ultrastructure of the clinically normal testicle (Group A) in the Zebu bull resembled that of Bos taurus. In testicles with a slight to moderate reduction of testicular consistency (Group B) degenerated primary spermatocytes and spermatids were common at all stages of the seminiferous cycle. Abnormalities in the condensation of the chromatin, acrosomal defects, and the presence of degenerated cells and cellular debris were the most common of disturbances found. In testicles from bulls with a marked reduction of testicular consistency (Group C) the seminiferous epithelium of most tubules showed degenerative changes, thereby making it impossible to classify the stage of the cycle. The changes were mainly restricted to spermatocytes and spermatids, whose relative numbers were reduced. The number of cells undergoing meiotic divisions was also greatly reduced. Changes in the spermatids were also found including the appearance of severe acrosomal defects, such as acrosomal pouches, the failure of nuclear elongation and clear defects in chromatin condensation. The present ultrastructural findings in Bos indicus do not differ from the picture of normal testicular structure and of testicular degeneration usually found in Bos taurus bulls. PMID- 1496867 TI - Obstructive hydrocephalus produced by parasitic granulomas in a dog. AB - We present a case of a young dog exhibiting internal hydrocephalus, associated with parasitic granulomas within the ventricular system, inflammatory changes in the periventricular brain tissue and stenosis of the mesencephalic aqueduct. Reference is made to possible causes of these lesions in animals and man. PMID- 1496869 TI - [The possibility of Yersinia pseudotuberculosis transmission via the soil-plant animal chain (a preliminary report)]. PMID- 1496868 TI - Intravenous and intraruminal administration of short chain fatty acids increase the potential difference across the sheep rumen epithelium. AB - The effect of intraruminal loads of a propionate/butyrate mixture and of intravenous administration of butyrate on the potential difference across the rumen epithelium (PD) was studied in conscious sheep. The PD was elevated during the measurement period 5 to 15 minutes after intraruminal loading with a propionate/butyrate mixture. Intravenously injected butyrate caused a prompt transitory increase in PD. The results show that both intraruminal and intravenous administration of certain short chain fatty acids stimulated the PD indicating altered ion transport properties across the rumen epithelium. PMID- 1496870 TI - [The effect of fermented-milk bifidumbacterin on the intestinal microflora of test pilots]. AB - Bacteriological study of intestinal microflora in test pilots, regularly exposed to excessive physical, as well as nervous and emotional strain, has revealed changes in the composition of their intestinal microflora. Correction of microflora by means of bifidumbacterin, a curative lactic fermentation alimentary product, was carried out. Rapid and effective restoration of intestinal microflora and improvement of the general state of patients were noted, which made it possible to recommend this product as a prophylactic remedy for subjects at risk of development of dysbiotic disturbances. PMID- 1496871 TI - [Expert research on sera yielding false-positive results for HIV antibodies during screening]. AB - The significance of different serological methods and assay systems for the verification of false positive cases of HIV infection has been analyzed on the basis of materials obtained in arbitration studies. As demonstrated by this analysis, the use of such highly specific and sensitive systems as Huma-Lab, Enzygnost, Serodia and Erythrorecombinant has made it possible to obtain a reliable result as early as at the first stage of expert diagnosis in the enzyme immunoassay and the agglutination test. The methods of radioimmunoprecipitation and indirect immunofluorescence have permitted a more precise differentiation of doubtful results than that achieved by immune blotting. PMID- 1496872 TI - [The diagnostic value of different test systems for the screening determination of antibodies to the human immunodeficiency virus]. AB - Evaluation of the quality of enzyme immunoassay (EIA) systems by their sensitivity and specificity is inadequate, mainly due to the impossibility of detecting early or latent HIV infection in humans as it manifests by seroconversion only to a few HIV proteins. The additional evaluation criterion (confirmation rate) has been introduced, and an original method for the integral evaluation of the quality of assay systems intended for the diagnosis of HIV infection by EIA techniques has been proposed. PMID- 1496874 TI - [Pasteurized milk as a factor in the transmission of the causative agents of yersiniosis]. AB - From 43 (35.8%) out of 120 samples of pasteurized milk used by volunteers 182 cultures of five Yersinia species--Y. enterocolitica, biovar 1 (70.3%), Y. intermedia (18.1%), Y. frederiksenii (7.7%), Y. kristensenii (3.3%) and Y. aldovae (0.5%)--were isolated in the course of bacteriological studies carried out in 1987-1990. The isolated Yersinia cultures belonged to nonpathogenic pyraminidaze-positive serovars. Yersinia pathogenic bio/serovars (4/O3, 2/O9, 1B/O8) were not detected. No deviations from the normal state were registered in the volunteers drinking pasteurized milk, and Yersinia could be isolated from their feces only during the first 3 days following milk consumption. In 390 patients examined for the presence of Yersinia infections the isolation rate of Yersinia of biovar 1 (99.6% of the cultures) varied between 4.4% and 21.3% and correlated with the increase of the isolation rate from milk (13.6% to 53.9%). The results of the study suggest that unboiled pasteurized milk contributes to the spread of Yersinia carriership among the population. PMID- 1496873 TI - [The formation of host-parasite relationships in an experimental mixed pathology of opisthorchiasis-tuberculosis as dependent on the phase of the Opisthorchis infestation]. AB - Superinfection of animals having Opisthorchis invasion with Mycobacterium tuberculosis leads to destabilization of host-parasite relationships in opisthorchiasis and formation of new host-parasitocenotic interrelations whose manifestation depends on the phase of the invasive process. At the acute invasive phase of mixed pathology (2 weeks) the activity of the host's immune system increases, while the biological activity of helminths and the number of M. tuberculosis colonies decrease. And on the contrary, at the subacute phase of mixed pathology (2.5 months) the activity of the host's immune system decreases, while the reproductive activity of helminths and the isolation rate of M. tuberculosis from pulmonary tissue increases in comparison with the groups of animals with monoinvasion and monoinfection. PMID- 1496875 TI - [The morphological assessment of the safety and protective activity of the vaccinal strain Salmonella typhimurium 274]. PMID- 1496876 TI - [Staphylococci in the microbiocenosis of the skin of the hands]. AB - The skin autoflora on the pad of a forefinger and the back and palm of a hand was studied in 40 healthy males aged 18-60 years by the modified washing and scraping method of P. Williamson and A. Kligman. 638 cultures of aerobic microorganisms, including coccal (55.3%) and bacilliform (44.7%) microbes, were isolated. In 6 persons (15%) coagulase-positive staphylococci were detected. Out of 10 coagulase negative species of this genus, S. epidermidis, S. saprophyticus and S. warneri occurred most frequently on the skin of hands. The highest density of bacterial populations (10.970 +/- +/- 1.845 cells/sq. cm) was registered on the back of hands, the surface of palms was found to have somewhat lower density (8.679 +/- 1.282 cells/sq. sm) and the skin of forefingers, the lowest density of bacterial populations (6.878 +/- +/- 1.137 cells/sq. sm). 17.5% of examined persons were found to be carriers with S. aureus isolated from their nasal mucosa. S. aureus isolated from the skin surface and the nasal cavity of different persons belonged to different phage variants, but S. aureus isolated from the nasal cavity and the skin of the same person belonged to one phage variant. PMID- 1496877 TI - [The correction of the functional activity of alveolar macrophages in inducing a primary immune response in influenza]. AB - The functional activity of alveolar macrophages obtained from mice, both healthy and infected with influenza virus A/Aichi 2/68 (H3N2), as manifested by their capacity to initiate the development of primary immune response to sheep red blood cells and Escherichia coli lipopolysaccharide after the transfer of these macrophages to intact syngeneic recipients was studied. The capacity of alveolar macrophages to perform antigen-presenting functions in the induction of humoral immune response was shown, and at the same time the development of experimental influenza infection was found to essentially decrease these properties. The injection of the immunomodulating agent diuciphon into experimental mice somewhat enhanced the immune response after the syngeneic transfer of alveolar macrophages from infected mice to intact recipients. PMID- 1496878 TI - [The opsonizing activity of the sera of hamadryas baboons immunized with a preparation of the outer membranes of Francisella tularensis (based on data from the luminol-dependent luminescence method)]. AB - The opsonizing properties of sera obtained from hamadryas baboons immunized with the preparation of F. tularensis outer membranes (OM) were studied with the use of luminol-dependent chemiluminescence (CL) of whole blood. The immunization of monkeys with the OM preparation was shown to lead to the formation of functionally active antibodies possessing opsonizing properties with respect to virulent F. tularensis. Immune sera obtained from the animals immunized with live vaccine and from those immunized with OM preparation had no essential differences in their opsonizing properties. The level of IgG antibodies in immune sera correlated with the CL parameters of whole blood in the presence of F. tularensis opsonized with these sera. Increased CL of phagocytes observed after addition of bacteria and immune sera under test to whole blood taken from a nonimmune donor made it possible to evaluate the functional activity of antibodies, thus permitting its use as a test for the evaluation of the effectiveness of new vaccine preparations. PMID- 1496879 TI - [The antigenic and allergenic properties of an extract from the house dust mite Dermatophagoides farinae]. AB - To evaluate the antigenic composition and allergenic activity of D. farinae extracts, the methods of rocket and cross immunoelectrophoresis, gel chromatography and the inhibition of the radioallergosorbent test have been used. The presence of 9-20 antigenic components has been established. The fractions of the extract with a molecular weight of 10-200 kD possessed the highest capacity of inhibiting the binding of specific IgE antibodies from the pool of sera from patients sensitized to D. farinae. PMID- 1496880 TI - [Ige and allergen-specific IgE antibodies in acute stenosis of the upper respiratory tract in children]. PMID- 1496881 TI - [Experience with the use of an immunoglobulin erythrocyte preparation for the early laboratory diagnosis of pseudotuberculosis]. AB - An immunoglobulin erythrocytic preparation for the rapid detection of Yersinia pseudotuberculosis was developed. The preparation was shown to be specific and sufficiently sensitive (8 x 10(5) microbial cells/ml). The preparation was used for the examination of 102 patients; in 62 of these patients the diagnosis was confirmed by means of common laboratory and clinical methods. Y. pseudotuberculosis antigen was detected in the blood of 39 patients (63%), and in 12 patients (29.4%) the results of traditional laboratory tests were negative. In 19 out of 23 patients the coincidence of the results of bacteriological and seroindication study was registered. During the study of the remaining 40 patients the antigen was detected only in 6 patients, including 3 patients with enteric yersiniosis. PMID- 1496882 TI - [Territorial differences in the nature of the etiological structure of shigellosis--a pattern or chance?]. PMID- 1496883 TI - [The biological properties of Bifidobacterium]. AB - The possibility of the formation of exoenzymes, such as DNAase, RNAase and hemolysin, by bifidobacteria was studied in comparison with their acid-forming and adhesive activity. Bifidobacterium reference strains, originally isolated from healthy adults and children, were studied. The study involved altogether 73 strains of bifidobacteria, including 24 B. bifidum strains, 13 B. adolescentis strains, 7 B. infantis strains, 10 B. breve strains and 19 B. longum strains. The bifidobacteria under study were shown to differ not only in the presence and activity of properties useful for macroorganisms, but also in the presence of enzymes having depolymerizing activity (DNAase, hemolysin). Thus, out of 73 strains under study 9 proved to be DNAase-positive and 6, hemolysin positive. At the same time a specific feature of bifidobacteria was their high acid-forming activity with the complete absence of RNAase activity and insignificant DNAase- and hemolysin-forming activity. PMID- 1496884 TI - [The effect of low temperature on the virulence of pathogenic bacteria]. PMID- 1496885 TI - [The functional activity of T-lymphocytes in candidiasis]. PMID- 1496886 TI - [The mechanisms of bacterial persistence]. PMID- 1496887 TI - [The absence of differences between El Tor cholera and classic cholera]. PMID- 1496888 TI - [The effect of different bacterial preparations in combination with total gnotobiological isolation on the survival of animals with experimental acute radiation sickness]. PMID- 1496889 TI - Human perilabyrinthine bone dynamics. A functional approach to temporal bone histology. PMID- 1496890 TI - The clinical drug trial in Meniere's disease with emphasis on the effect of betahistine SR. PMID- 1496891 TI - Use effectiveness of the Cytobrush in the primary care setting. AB - BACKGROUND: Numerous studies indicate that Papanicolaou smears contain better cellular material when the technique for collecting the sample employs the Zelsmyn Cytobrush. Few studies, however, have examined its ability to increase the percentage of abnormal Papanicolaou smear results in actual clinical practice. METHODS: This study looked at 7999 Papanicolaou smears done by 46 primary care physicians to determine the percentage of abnormal results during two different periods. The Cytobrush technique was then implemented; and after 6029 Papanicolaou smears, the percentage of smears with abnormal findings was recalculated. RESULTS: The proportion of Papanicolaou smears demonstrating significantly abnormal cells remained constant during the three observation periods: 1.81 percent during the first period, 1.96 percent during the second period (before the Cytobrush technique was implemented), and 1.96 percent during the third period (after the Cytobrush technique was implemented). CONCLUSIONS: It seems logical that Papanicolaou smears containing better cellular material from the squamocolumnar junction would increase the yield of Papanicolaou smears with cancerous and precancerous cells. Our study, however, did not confirm this supposition. While evaluation of Papanicolaou smear technique based on quantity and quality of cellular material is important, we believe the effectiveness of any technique must be evaluated from another perspective--the actual practice setting. PMID- 1496892 TI - Use of deep venous thrombosis prophylaxis by family physicians. AB - BACKGROUND: Accumulated data indicate that the administration of low-dose subcutaneous heparin reduces the incidence of deep venous thrombosis in high-risk surgical and medical patients. Because deep venous thrombosis predisposes to pulmonary embolism, it is generally accepted that reducing deep venous thrombosis will reduce pulmonary embolism, the most common preventable cause of death in hospitalized patients. There are few data, however, regarding physicians' use of heparin for deep venous thrombosis prophylaxis in medical patients. METHODS: We reviewed charts of medical patients aged 50 years and older who were admitted to family practice services in a community teaching hospital and excluded patients who were not candidates for heparin prophylaxis. RESULTS: Eighty (65 percent) of 123 patients received heparin for deep venous thrombosis prophylaxis. Patients admitted to a residency teaching service were more likely to receive heparin for deep venous thrombosis prophylaxis than were patients admitted to nonteaching services (odds ratio 3.37, 95 percent confidence interval 1.26-9.21, P = 0.012). An association between the patient's number of risk factors for deep venous thrombosis and likelihood of receiving deep venous thrombosis prophylaxis approached statistical significance (P = 0.078). CONCLUSIONS: In our institution, heparin for deep venous thrombosis prophylaxis is frequently but not uniformly prescribed for appropriately selected family practice inpatients. No similar data for nonsurgical patients were found for comparison. PMID- 1496893 TI - Evaluation of a latex agglutination test for the identification of Candida species in vaginal discharge. AB - BACKGROUND: The diagnosis of Candida vulvovaginitis using historical symptoms, pelvic examination findings, and results of traditional in-office laboratory tests is often inaccurate. Although Candida cultures can verify the diagnosis, they are not routinely used. METHODS: We prospectively compared the accuracy of a commercially available, in-office, rapid, latex agglutination test (CandidaSure) for the identification of Candida species with results from Candida culture. RESULTS: The sensitivity of the latex agglutination test was 66 percent and the specificity was 63 percent when compared with Candida culture results in patients with vaginal symptoms. When compared with a microscopic evaluation using potassium hydroxide (KOH), the CandidaSure test had greater sensitivity but a lower specificity. In 74 percent of cases with a positive KOH preparation, yeast forms were present on culture, and little was gained by adding the CandidaSure test in this situation. The addition of the CandidaSure test in those cases with a negative KOH preparation resulted in increased sensitivity but also increased the number of false-positive diagnoses. CONCLUSIONS: The CandidaSure test has greater sensitivity than the KOH preparation, but it is less predictive of a positive culture. Because of this limitation, Candida should be documented by culture for any patient who has recurrent or persistent disease and a negative KOH slide. PMID- 1496895 TI - The complications of immobility in the elderly stroke patient. AB - BACKGROUND: Approximately 500,000 persons in the United States suffer a stroke each year; the majority of these individuals are 65 years of age or older. The neurological impairment occurring as the result of stroke can lead to both acute and chronic disability. Further medical complication and disability are often the result of immobility-related illness that occurs while the patient is still in the hospital. METHODS: A MEDLINE search for articles published from 1980 to 1990 was made using the key words immobilization and stroke rehabilitation. The bibliographies of these articles, key rehabilitation and geriatric textbooks, the bibliographies of these textbooks, and the authors' personal files were also sources of information. RESULTS AND CONCLUSIONS: Immobility-related medical complication and disability can be substantially reduced by identifying risk factors and applying preventive measures. As long-term providers of medical care, family physicians are in a position to devise a preventive care plan for immobility-related disability and to appreciate the beneficial effects of such a plan on patient outcome. PMID- 1496894 TI - Longitudinal study of a diabetes education and care intervention: predictors of improved glycemic control. AB - BACKGROUND: This study prospectively identifies those characteristics of office patients with diabetes that predict subsequent improvement in glycemic control in response to an educational intervention. METHODS: Data on demographic factors, disease characteristics, and glycemic control were obtained on a consecutive series of patients referred by their primary physician to a 4-day outpatient diabetes education and care program. Follow-up measurement of glycosylated hemoglobin (HbA1C) was obtained from the same laboratory 2 months later. Analysis using logistic response models identified baseline characteristics associated with improved HbA1C. RESULTS: Among the 169 study subjects, 74 (44 percent) had at least a 20 percent improvement in HbA1C levels 2 months after the program. Among these subjects, mean HbA1C level was 10.6 percent before and 7.4 percent 2 months after the program. Factors associated with improvement in HbA1C values in bivariate and multivariate logistic models included duration of diabetes less than 2 years (risk ratio = 1.90, 95 percent confidence interval (CI) 1.30-2.76) and initial HbA1C level greater than 10 percent (risk ratio = 2.75, 95 percent CI 2.08-4.01). Baseline functional status, health locus of control, social support, knowledge of diabetes self-care, age, weight as percentage of ideal body weight, age at diagnosis, race, sex, family history of diabetes, type of diabetes, and mode of treatment were not significant predictors of improved HbA1C. CONCLUSIONS: Patients with shorter duration of diabetes and poor baseline glycemic control were most likely to have clinically significant glycemic responses to this program. Severity of disease and regression to the mean were unable to account for this association, leaving unanswered the question of the mechanism of this association. The data also identified a group of patients who do not respond well to this educational approach and for whom novel approaches to behavior change should be considered. PMID- 1496896 TI - Venomous snakebite: past, present, and future treatment options. AB - BACKGROUND: Venomous snakebites continue to cause great morbidity, and treatment options are confusing the attending physician. In the United States approximately 45,000 snakebites occur each year, of which some 8000 are by 20 species of venomous snakes. METHODS: Information on venomous snakes and snakebite treatment was gathered from the libraries of the Wilderness Medical Society and the Rocky Mountain Center for Wilderness Medicine in Boise, Idaho (co-supported by the Boise State University and the Family Practice Residency of Idaho), as well as from current literature files of physicians practicing wilderness medicine. RESULTS AND CONCLUSIONS: Three genera of venomous snakes account for the majority of poisonous snake envenomations in this country. Most hospitalized victims are bitten either by rattlesnakes or copperheads or by unidentified snakes. Most of these bites occur during the summer months and are found on the extremities. Field treatment focuses on the application of a vacuum extractor and transportation to the nearest medical facility. Although constriction band use can be helpful, tourniquets, incision and suction, and ice therapy are contraindicated. Electric shock therapy is of no use and could cause serious injury. Hospital management focuses on rapid clinical evaluation and laboratory tests to establish the degree of envenomation, looking for clotting abnormalities. If envenomation has occurred and is reactive, polyvalent antivenin should be administered according to the degree of envenomation. Errors in diagnosis and treatment result in increased morbidity and put attending physicians at risk for litigation. Prevention remains the most successful approach to snakebite management. PMID- 1496897 TI - Can physicians be induced to resume obstetric practice? AB - BACKGROUND: Decreased numbers of obstetric providers during the last decade have limited access to obstetrics care, especially for some groups of women. Increasing or stabilizing the number of providers could increase access. METHODS: A questionnaire was mailed in 1989 to 1965 Washington State family physicians and obstetricians to determine their attitudes toward the practice of obstetrics. Sixty-six percent of physicians responded to the survey. RESULTS: Of those who had quit obstetrics in the previous 3 years, 42 percent of responding family physicians and 19 percent of responding obstetricians would consider resuming. Those family physicians willing to consider resuming their obstetric practices were more likely to have been in practice fewer years, employed by a health maintenance organization (HMO), or located in a rural area. A majority of all respondents cited excessive malpractice premiums and fear of malpractice suit as reasons for stopping obstetric practice. Family physicians willing to consider resuming obstetrics were more concerned about the overall number of obstetric providers in their area. Rural family physicians willing to consider resuming obstetrics listed poor backup or shared call more often as a reason they had quit. CONCLUSIONS: Attention targeted to the concerns of family physicians who have been in practice for a short time, who work for HMOs, or who are in rural practice might help induce some physicians to resume obstetrics. PMID- 1496898 TI - Will family physicians really return to obstetrics if malpractice insurance premiums decline? AB - BACKGROUND: The loss of family physicians as obstetrics providers during the last decade has had a significant impact on access to obstetric services, especially for rural populations. The expense of malpractice premiums has been cited often as a reason for physicians' discontinuation of this service. METHODS: Seventy-six family physicians in northern California who recently discontinued obstetrics were surveyed regarding their decisions related to obstetric practice. Those physicians who indicated that a decrease in malpractice premiums would allow them to consider resuming obstetrics were resurveyed by telephone the following year. This telephone survey occurred following a 25 percent decrease in malpractice premiums for obstetrics by the major malpractice insurance carrier for family physicians practicing obstetrics in the study area. RESULTS: Twenty-nine of the 76 physicians in the original survey who had recently discontinued obstetrics stated they would consider resuming if conditions changed. Twenty-six (90 percent) of these physicians indicated that malpractice premiums needed to change for them to consider resuming obstetrics. Following the reduction in premiums, none of these physicians reported plans to resume obstetrics or even a likelihood that they would be resuming obstetrics. CONCLUSION: This study found that family physicians who discontinued obstetrics and cited malpractice premiums as a barrier to resuming obstetrics are unlikely to resume when rates decline. This finding suggests that other issues might be equally or more important in this decision. PMID- 1496899 TI - A five-step "microskills" model of clinical teaching. AB - Teaching family practice residents in a clinical setting is a complex and challenging endeavor, especially for community family physicians teaching part time and junior faculty members beginning their academic careers. We present a five-step model of clinical teaching that utilizes simple, discrete teaching behaviors or "microskills." The five microskills that make up the model are (1) get a commitment, (2) probe for supporting evidence, (3) teach general rules, (4) reinforce what was done right, and (5) correct mistakes. The microskills are easy to learn and can be readily used as a framework for most clinical teaching encounters. The model has been well received by both community family physicians interested in teaching and newer residency faculty members. PMID- 1496900 TI - Dermatologic manifestations of giardiasis. AB - We have presented a case of atopic dermatitis associated with Giardia lamblia infection, which has not been previously described. Review of the world literature shows an association between giardiasis and urticaria. Other allergic phenomena, such as angioedema and possibly arthropathy, also might be associated with this infection. When confronted with these clinical problems, giardiasis should be included in the differential diagnosis. As these complications respond to specific therapy, identification of this organism as its cause can be particularly rewarding. PMID- 1496902 TI - Sarcoidosis as a testicular mass. PMID- 1496901 TI - Oxygen saturation in high-altitude pulmonary edema. PMID- 1496903 TI - Family physicians performing obstetrics: is malpractice liability the only obstacle? PMID- 1496905 TI - Physical activity and coronary heart disease. PMID- 1496904 TI - Recruitment to family practice residencies. PMID- 1496906 TI - Carwash injuries. PMID- 1496907 TI - Colposcopy training. PMID- 1496908 TI - [Detoxification of alcoholic patients in the hospital and in ambulatory care: discriminating factors]. PMID- 1496909 TI - [ICD-9 versus DSM-III in the psychoses: anamnestic and catamnestic implications]. AB - We pretend with our study to compare the DSM-III diagnostic criteria with ICD-9 diagnostic criteria for psychotic episodes and to look for the diagnostic stability for both classifications. We studied 79 first psychotic episodes following ICD-9 and retrospectively we applied the DSM-III diagnostic criteria to the same patients. The mean follow up time was 46.6 +/- 6.7 months. In the ICD-9 the schizophrenic psychoses represented the main diagnostic group, not only the day they were discharged from the hospital 31.6% but also in the follow up 39.2%. On the other hand in the DSM-III, in the discharge day the schizophreniform disorder was the more frequent diagnostic 24%, while in the follow up the schizophrenic disorder came to the first position 32.9%. In the ICD-9 there was a 15.1% of diagnostic changes and in the DSM-III nearly the double 30.3%. In both classifications the unspecified and the atypical suffered a great diagnostic mobility; in both nosologies the schizophrenia was the most unchangeable diagnosis, no patient discharged with this diagnosis changed to another in the follow up. ICD-9 could be said that has a great sensitivity and an acceptable specificity for this entities, and DSM-III would have a moderate sensitivity but a very diagnostic specificity for these disorders. PMID- 1496910 TI - [Differential phenomenology of the paranoid psychoses in epilepsy]. AB - First, the author makes reference to the psycho pathological and nosological questions associated with paranoid and schizophrenia-like psychoses in epilepsy and in particular to the non resolved problem of a distinction between these epileptic syndromes and the ones of schizophrenia. Starting from a phenomenological analysis of basic existential structures such as encounter or interpersonality, temporality and spatiality in a typical case of paranoid psychosis in epilepsy, the author tries to establish formal criteria which allow to distinguish these psychoses from schizophrenia. Thus it could be demonstrated that the structure of the encounter in the psychotic epileptic is quite conserved, both in what refers to the real and the delusional partner. His spatiality is characterized by the phenomenon of narrowness and his temporality by harassment, being necessary to underline the fact that, unlike what happens in schizophrenia, in the paranoid psychoses of epilepsy the space maintains its unity and the time its continuity. We could summarize the substantive difference between both types of paranoid psychoses with the following words: in paranoid syndromes in epilepsy what occurs is a change of state "within the world", while in schizophrenia it is a rather a modification of the "being-in-the world" itself or, with other words, it deals with a going out from the world constituted as community. PMID- 1496911 TI - [Family response and alcohol consumption]. AB - The present study has its main objective the analysis of family responses to excessive alcohol consumption. For this we used data derived from a cross sectional epidemiological community survey directed to investigate, in a random sample of 1.800 persons of 18 to 65 years of age and representative of the population of Cantabria community responses to alcohol consumption. We applied, among other instruments, a questionnaire designed by the WHO for exploring alcohol consumption, and which has being extensively used in other settings. We found, among other things, that: i) The concern about parents excessive alcohol consumption has different repercussions depending of the sex of their children, thus producing more alcohol related problems in males; ii) The concern for the alcohol consumption of ones partner is more often seeing in females, thus females tend to be more sensitive to these problems, and also they tend to detect them earlier and be more tolerant to them; iii) Persons who worry for the alcohol consumption of their partners usually have also had parents with such sort of problems; iv) And lastly about 11% of males and 13% of females with adolescent children tend to worry about the children' excessive alcohol consumption. PMID- 1496912 TI - [Depressive states in multiple sclerosis. Critical bibliographic review]. AB - The aim of this paper is to review the question of depression in patients with multiple sclerosis (MS). Morbidity and methodological difficulties in the investigation of depressive states in MS are analyzed. Prevalence of depression in MS in previous series is critically compared. The role of chronic invalidity and topography of demyelinating lesions in the development of depression are considered. We also review the treatment of depressive states and future guidelines for investigation of this topic. PMID- 1496913 TI - Transport and in vivo elimination of cysteinyl leukotrienes. AB - Transport processes control not only synthesis and release of LTC4 but also the elimination and excretion of LTC4 and its metabolites. (i) A primary-active ATP dependent export carrier mediates the release of LTC4 from a leukotriene generating cell, as exemplified by mastocytoma cells, and as measured in mastocytoma plasma membrane vesicles (2). (ii) Release of cysteinyl leukotrienes into the blood circulation is followed by a rapid elimination with an initial half-life of 38 sec in rats and 4.0 min in man, as measured with the labeled, representative LTC4 catabolite, N-acetyl-LTE4. (iii) 11C-labeled N-acetyl-LTE4 can serve for non-invasive studies on cysteinyl leukotriene elimination and excretion by the liver and kidney in the intact organism using positron emission tomography. An impairment of leukotriene transport from the liver across the canalicular membrane into bile, studied in mutant rats and in extrahepatic cholestasis, leads to a compensatory diversion of cysteinyl leukotriene elimination to the kidney. N-Acetyl-LTE4 labeled with a short-lived positron emitting isotope provides quantitative insight into the pathways of cysteinyl leukotriene elimination in vivo. (iv) Cysteinyl leukotriene export from the liver into bile is mediated by an ATP-dependent primary-active export carrier. This decisive step in cysteinyl leukotriene elimination has been characterized in hepatocyte canalicular membrane vesicles (3). The leukotriene exporter is deficient in transport mutant rats. The leukotriene carrier is distinct from other ATP-dependent export carriers identified in this membrane domain, such as the ATP-dependent bile salt export carrier (25) and the multidrug export carrier (27). PMID- 1496914 TI - Antimicrobial peptides of frog skin. AB - A mechanism of action for frog skin antimicrobial peptides has been proposed, based on the amphipathic nature of the peptides when they contact bacterial surfaces. This results in anion channel formation and penetration of the membrane which allows efflux of OH- and uncoupling of respiration in the bacteria. The question of occurrence of human antimicrobial peptides analogous to those in frogs has not been answered but early studies indicate that Erspamer's prediction is correct. PMID- 1496915 TI - The regulatory protein of liver glucokinase. AB - Fructose, sorbitol and D-glyceraldehyde stimulate the rate of glucose phosphorylation in isolated hepatocytes. This effect is mediated by fructose 1 phosphate, which releases the inhibition exerted by a regulatory protein on liver glucokinase. In the presence of fructose 6-phosphate, the regulatory protein binds to, and inhibits, liver glucokinase. Fructose 1-phosphate antagonizes this inhibition by causing dissociation of the glucokinase-regulatory protein complex. Both phosphate esters act by binding to the regulatory protein, and by presumably causing changes in its conformation. The regulatory protein behaves as a fully competitive inhibitor. It inhibits liver glucokinase from various species, and rat islet glucokinase, but has no effect on hexokinases from mammalian tissues or from yeast, or on glucokinase from microorganisms. Kinetic studies indicate that the regulatory protein binds to glucokinase at a site distinct from the catalytic site. Several phosphate esters, mainly polyol-phosphates, were found to mimick the effect of fructose 6-phosphate. The most potent is sorbitol 6-phosphate, suggesting that fructose 6-phosphate is recognized by the regulatory protein in its open-chain configuration. Other phosphate esters and Pi have a fructose 1 phosphate-like effect. The stimulatory effect of fructose on glucose phosphorylation is observed not only in isolated hepatocytes but also in the livers of anesthetized rats. This suggests that fructose could be a nutritional signal causing an increase in the hepatic glucose uptake. PMID- 1496917 TI - The utility of an anti-fos ribozyme in reversing cisplatin resistance in human carcinomas. AB - The results presented here demonstrate that expression of a fos ribozyme limits Fos protein synthesis and enhances sensitivity of A2780DDP cells to antineoplastic agents, including cisplatin. Moreover, the reversal of this resistance is associated with down-regulation of dTMP synthase, DNA polymerase beta, topoisomerase I and hMTII-A, genes previously linked to DNA synthesis and repair. Thus these studies further implicate the role of the c-fos gene in DNA synthesis through modulation of expression of dTMP syntase, DNA polymerase beta and topoisomerase I. Finally, the use of ribozymes to circumvent drug resistance suggests their potential utility as agents to inhibit tumor cell growth. PMID- 1496916 TI - Effect of Ha-ras on mitogen-induced Ca(2+)- and K(+)-fluxes. AB - Transforming Ha-ras enhances the mitogen-induced activation of both the Ca(2+) influx and the furosemide-sensitive Na+/K+/2Cl-cotransporter. Both systems represent essential early steps of mitogenic signal transduction in NIH 3T3 fibroblasts. PMID- 1496918 TI - Common characteristics of normal and cancerous growth in vivo. PMID- 1496920 TI - Regulation of thymidine kinase during growth, cell cycle and differentiation. PMID- 1496919 TI - Factors affecting the mRNA levels for the non-heme iron and effector-binding subunits of ribonucleotide reductase. AB - Ribonucleotide reductase which catalyzes the rate-limiting step in the de novo synthesis of dNTPs is composed of two non-identical protein subunits which are not under coordinate control in terms of synthesis and degradation. The mRNAs for the effector-binding (EB) and non-heme iron (NHI) subunits are likewise not under coordinate control during cell cycle traverse. Inhibitors directed at the specific subunits of ribonucleotide reductase block DNA synthesis. These current studies show that drugs such as IMPY or hydroxyurea which specifically inhibit the NHI subunit cause a marked increase in the steady-state level of the mRNA for the NHI subunit while resulting in a decrease in the level of mRNA for the EB subunit. In cells treated with deoxyadenosine, the patterns of the mRNAs for the NHI and EB subunits were different from those seen in the IMPY- or hydroxyurea treated cells. Control experiments utilizing inhibitors (aphidicolin or araC) directed at DNA polymerase showed that the pattern of changes in the mRNA levels for the NHI and EB subunits were specific for the reductase inhibitors. These changes in the mRNAs for the NHI and EB subunits may be due to drug-induced alterations in transcription rates and/or degradation rates for the specific mRNAs. PMID- 1496921 TI - Growth hormone regulation of hepatic cytochrome P450 expression in the rat. AB - GH by means of its sexually differentiated secretory pattern is the predominant regulator of the expression of cytochrome P450 enzymes responsible for a sexual dimorphism of hepatic steroid metabolism. Other hormones, such as gonadal, thyroid and glucocorticoid hormones, as well as insulin appear to modulate the sexually differentiated expression of these enzymes. The major constitutively expressed sex specific forms of P450, belonging to the P4502C-subfamily, have been shown to be regulated by GH at the level of transcription. However, the GH postreceptor events leading to increased or decreased transcriptional activity are essentially unknown. Neither is the functional role of the soluble GH binding protein yet resolved. On-going protein synthesis is a prerequisite for GH transcriptional activation of the female specific P4502C12 but not for all GH effects in the hepatocyte. With regard to signalling mechanisms PKC activity appears to be permissive for the GH induction of P4502C12 but some as yet unidentified factor/kinase(s) may also be activated. The transcriptional control exerted on the rat P4502C-gene subfamily by the pattern of GH secretion offers a versatile tool to elucidate the molecular mechanisms of GH regulation of cytochrome P450 expression. PMID- 1496923 TI - Regulation of mitochondrial carnitine palmitoyl transferases from liver and extrahepatic tissues. AB - Developments in our understanding of the complex CPT enzyme system over the past ten years have been reviewed. Liver CPT1, which is probably distinct from that in several extrahepatic tissues, is subject to up- or down-regulation of its activity and kinetic properties with changing physiological state. Evidence is now accumulating to support the notion that the catalytic and malonyl-CoA-binding entities of CPT1 are separate polypeptides. PMID- 1496922 TI - Purification, characterization, regulation and molecular cloning of mitochondrial protein kinases. AB - The mitochondrial kinases responsible for the phosphorylation and inactivation of rat heart pyruvate dehydrogenase complex and the rat liver and heart branched chain alpha-ketoacid dehydrogenase complexes have been purified to homogeneity. The branched-chain alpha-ketoacid dehydrogenase kinase is composed of one subunit with a molecular weight of 44 kDa; pyruvate dehydrogenase kinase has two subunits with molecular weights of 48 (alpha) and 45 kDa (beta). Proteolysis maps of branched-chain alpha-ketoacid dehydrogenase kinase and the two subunits of pyruvate dehydrogenase kinase are different, suggesting that all subunits are different entities. The alpha subunit of the rat heart pyruvate dehydrogenase kinase was selectively cleaved by chymotrypsin with concomitant loss of kinase activity, as previously shown for the bovine kidney enzyme, suggesting that the catalytic activity of pyruvate dehydrogenase kinase resides in this subunit. Polyclonal antibodies against branched-chain alpha-ketoacid dehydrogenase kinase, purified by an epitope selection method, bound only to the 44 kDa polypeptide of the branched-chain alpha-ketoacid dehydrogenase complex, substantiating that the 44 kDa protein corresponds to the kinase for this complex. Both kinases exhibited strong substrate specificity toward their respective complexes and would not inactivate heterologous complexes. The kinases possessed slightly different substrate specificities toward histones. Phosphorylation and inactivation of the branched-chain alpha-ketoacid dehydrogenase complex by its purified kinase was inhibited by alpha-chloroisocaproate and dichloroacetate, established inhibitors of the phosphorylation of the complex. cDNAs encoding the branched-chain alpha ketoacid dehydrogenase kinase have been isolated from rat heart and rat liver lambda gt11 libraries. This represents the first successful cloning of a mitochondrial protein kinase. Preliminary data suggest that two different isoforms of the kinase may exist in different ratios in various tissues. No evidence was found for induction of the branched-chain alpha-ketoacid dehydrogenase complex nor its kinase by clofibric acid. Rather, clofibric acid is a potent inhibitor of the activity of the branched-chain alpha-ketoacid dehydrogenase kinase and this may be the molecular mechanism responsible for the myotonic effects of clofibric acid in man. PMID- 1496924 TI - Alanine glyoxylate aminotransferase deficiency: biochemical and molecular genetic lessons from the study of a human disease. AB - The decision to treat a patient with primary hyperoxaluria type 1 (PHI) by combined liver and kidney transplantation, the former to correct the metabolic lesion which was then thought to be deficiency of cytoplasmic 2 oxoglutarate:glyoxylate carboligase, and the latter to replace the organ which is destroyed, provided an opportunity to investigate the disease by modern biochemical methods. It was shown that 2-oxoglutarate:glyoxylate carboligase (the first decarboxylating component of 2-oxoglutarate dehydrogenase) is entirely mitochondrial so that deficiency of a cytoplasmic form of this enzyme could not be the cause of PHI. The deficient enzyme proved to be hepatic peroxisomal alanine:glyoxylate aminotransferase (AGT). The disease can be diagnosed enzymologically on percutaneous liver biopsies and this is possible for the fetus in utero. There are four types of genetically determined heterogeneity in PHI:(1) responsiveness and non-responsiveness to pharmacological doses of pyridoxine, in terms of an effect on the rate of oxalate production; (2) the presence or absence of residual catalytic AGT activity; (3) CRM+ and CRM-variants; (4) locational variation by virtue of which the enzyme (AGT) is mitochondrial and not peroxisomal. About one third of patients with PHI have residual AGT activity and at least a large proportion of these have mitochondrial and not peroxisomal AGT. The molecular features which guide peroxisomal and mitochondrial enzymes from their sites of synthesis into the appropriate organelle are reviewed and the possibilities for genetic variation in the relevant parts of the AGT molecule are discussed. The gene directing the synthesis of AGT has been cloned and sequenced, as has the AGT cDNA from a patient with mitochondrial AGT. Three point mutations causing amino acid substitution in the predicted AGT protein sequence have been identified: proline----leucine at residue 11, glycine----arginine at residue 170 and isoleucine----methionine at residue 340. The present evidence based on screening PHI patients and control subjects suggest that the substitution at residue 11, which cosegregates with that at residue 340, generates an amphiphilic alpha-helix which resembles mitochondrial targeting sequences but that misrouting of all the newly synthesized AGT into mitochondria requires the substitution at residue 170 which may act by impeding the entry of the enzyme into peroxisomes. The recognition of enzyme locational heterogeneity in PHI due to mutations affecting leader sequences should encourage a search for similar metabolic lesions in other inborn errors of metabolism affecting peroxisomal and/or mitochondrial enzymes. PMID- 1496925 TI - Morphological evidence of function-related localization of phospholipids in the cell nucleus. AB - The evidence accumulated in recent years on the presence of phospholipids inside the interphase nucleus needs a precise localization of the nuclear sites of accumulation, transport and degradation of these molecules. A very useful approach for monitoring the fine localization of nuclear phospholipids is represented by a recently developed technique using gold-conjugated phospholipases. In fact, in addition to the phospholipids organized in bilayers in the membrane, this technique identifies amorphous lipoprotein complexes present in different cell areas as well as in the nucleus. In this way and using sample preparation systems which reduce lipid removal and translocation, such as cryofixation, cryosectioning, embedding in hydrophylic resins and cryofracturing, we have analyzed the subnuclear localization of phospholipids in different experimental conditions. The results indicate that: in interphase the nuclear phospholipids are localized mainly in the interchromatin spaces and in the nucleolar domain; the observed co-localization of phospholipids and ribonucleoproteins suggests that phospholipids are involved in the mechanism of transport and release of the transcripts; the demonstrated release of ribonucleoproteins after phospholipase digestion suggests that phospholipids mediate the binding between ribonucleoproteins and the nuclear matrix; significant changes of the phospholipid localization occur in the different phases of the cell cycle or in the course of induced cell differentiation. PMID- 1496926 TI - Parasitic infections in women and their consequences. PMID- 1496927 TI - The interaction of Leishmania species with macrophages. PMID- 1496928 TI - The effects of trypanosomatids on insects. PMID- 1496929 TI - Echinococcus multilocularis infection: immunology and immunodiagnosis. PMID- 1496930 TI - The pathophysiology of malaria. PMID- 1496931 TI - A probability model for assessing exposure among respirator wearers: Part I- Description of the model. AB - The basic respirator equation states that the contaminant level inside a respirator (CI) is the product of the contaminant level outside the respirator (CO) and the decimal fraction penetration (P). On the basis of this relation, the authors present a probability model for the lognormal total distribution of CI levels among a respirator-wearing population; the model accounts for between wearer and within-wearer variability in both CO levels and P values. The assumptions underlying the model are shown to be consistent with current knowledge about the variability in CO levels and P values. The model provides the basis for assessing the probability of overexposure to acute toxicants and to chronic toxicants among a respirator-wearing population. PMID- 1496932 TI - A probability model for assessing exposure among respirator wearers: Part II Overexposure to chronic versus acute toxicants. AB - A model describing the lognormal total distribution of contaminant levels inside a respirator (CI) is applied to assessing the probability of toxicant overexposure among a population of respirator wearers; the model accounts for between-wearer and within-wearer variability in ambient exposure levels (CO) and decimal fraction respirator penetration (P) values. The three exceedance probabilities are defined as PrI, the proportion of all CI levels over the permissible exposure limit (PEL); PrII, the proportion of wearers with an arithmetic mean CI level over the PEL; and PrIII, the proportion of wearers with a 95th percentile CI value over the PEL. PrII is considered that fraction of the population overexposed to a chronic toxicant; PrIII is considered that fraction overexposed to an acute toxicant. The behavior of PrII and PrIII over a range of exposure parameters is explored. An important observation is that a respirator wearing population can have a substantial fraction of toxicant overexposure even though two conditions are met: (1) the P values for the population satisfy the criterion for the assigned protection factor (APF); and (2) the population arithmetic mean CO level is at or below the maximum use concentration (MUC), defined as APF x PEL. The authors recommend that the current MUCs for air purifying respirators be reduced by one-half to reduce the potential respirator wearing population fraction of overexposure and that appropriate exposure surveillance programs for all wearers be mandated. PMID- 1496933 TI - An approach to evaluating and correcting aerodynamic particle sizer measurements for phantom particle count creation. AB - An aerodynamic particle sizer (APS) can be used to make real-time measurements of the aerodynamic particle size distribution over the range of 0.5 to 32 microns. This instrument is very useful in conducting health-related aerosol measurements involving aerosol generation, respirator efficiency, and particulate sampling efficiency. One of the two signal processors within the APS can create spurious or phantom particle counts that can significantly affect relative measurements and calculated mass distributions. In the APS, particle size measurement is based upon a particle's transit time between two laser beams that are perpendicular to an accelerating airflow. The signal processors measure each particle's transit from the time between the two pulses of scattered light that are generated as the particle passes through the two laser beams. When only a single pulse from a particle is detected, another pulse can cause the recording of a randomly sized phantom particle. The small particle processor (SPP), which measures particle transit from the times in digital increments of 4 nanoseconds, can create phantom particles; the large particle processor (LPP), which measures particle transit times in digital increments of 66.67 nanoseconds, is designed to prevent the creation of phantom particles. These two processors overlap in the range of 5.2 to 15.4 microns.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1496934 TI - Exact expressions for the bias and variance of estimators of the mean of a lognormal distribution. AB - Exact mathematical expressions are given for the bias and variance of the arithmetic and maximum likelihood estimators of the first moment (mean) of a lognormal distribution. On the basis of these exact expressions, and without the need for simulation, statistics on the bias and variance have been computed for a range of sample sizes and geometric standard deviations. The results reaffirm that an unbiased maximum likelihood estimator exists that has minimum variance. Contrary to some recent recommendations, this is the preferred estimator if the data truly come from a lognormal distribution. PMID- 1496935 TI - Effect of the mosquito repellent DEET and long-wave ultraviolet radiation on permeation of the herbicide 2,4-D and the insecticide DDT in natural rubber gloves. AB - Studies were conducted to determine the effect of a commonly used insect repellent, DEET (N,N-diethyl-m-toluamide), on the permeability of rubber gloves used as chemical protective clothing (CPC) by pesticide applicators. Glove permeation analysis was conducted with an automated in vitro diffusion analysis (AIDA) method employing an in-house, flow-through permeation cell design. Permeation of 14C-ring-labeled 2,4-D (2,4-dichlorophenoxyacetic acid) in natural rubber glove material was 2.4 +/- 1.81% at 48 hr after treatment of the glove with 2,4-D applied with DEET; this was not significantly different (Student's t test; p less than 0.05) from 3.2 +/- 3.46% permeation of 2,4-D observed without DEET. Similarly, there was no significant difference between the permeation of pp'-DDT (1,1,1-trichloro-2,2-bis(4-chlorophenyl)ethane) applied with DEET (11.7 +/- 5.02%) and without DEET (11.4 +/- 4.86%) to natural rubber glove material. Scanning electron microscopy of the natural rubber glove material, however, demonstrated disruption of the surface ultrastructure following a 24-hr treatment with DEET. The AIDA analysis also suggested that exposure of the glove material to long-wave ultraviolet (UVA) radiation enhanced the glove permeability to 2,4-D (6.2 +/- 0.73% [+UVA]; 0.3% +/- 0.14% [-UVA]) but had no effect on the permeation of DDT. Because the CPC of pesticide applicators is commonly exposed to solar UVA, this finding may raise concerns about the efficacy and safety of CPC in general. PMID- 1496936 TI - Toxicological index and the presence in the workplace of chemical hazards for workers who breast-feed infants. AB - The increasing number of women in the workplace has made it more important than ever to ensure a safe work environment, particularly with respect to mothers who choose to breast-feed their babies. The Quebec Commission de la sante et de la securite du travail (CSST) Toxicological Index is fully involved in the provincial program for the protective reassignment of workers who breast-feed infants. The Infotox database provides peer-reviewed information concerning chemicals identified in the workplace that may appear in the mother's milk, possibly to be ingested by the breast-fed infant. Data extracted from the CSST computer system that holds information on 5,500 substances are presented. A total of 153 chemicals (2.7%) are recognized as being involved in some milk transfer. The strength of evidence is assessed with reference to strong or weak association (excretion or detection) in humans or in animals. Such an effect provides a useful basis for administrative decision involving protective reassignment as well as evaluation of work environment. Database users must be well informed about the identification of chemicals in breast milk because this is an essential step for the evaluation of the hazards of transferring chemicals encountered in the workplace from mother to baby. Actually, the main problem is that there are very few data in the scientific literature concerning milk transfer. PMID- 1496937 TI - Misuse of metered dose inhalers by house staff members. PMID- 1496938 TI - Pediatric medical advice enhanced with use of video. PMID- 1496939 TI - Predicting the course of bronchiolitis. PMID- 1496940 TI - Mitral valve prolapse. PMID- 1496941 TI - Drug abuse in The Netherlands. PMID- 1496942 TI - The artful dodge on pertussis vaccine. PMID- 1496943 TI - Molecular biology. A tool for elucidating the molecular mechanisms underlying disease. PMID- 1496944 TI - Prevention of perinatal transmission of the hepatitis B virus. Outcome of infants in a community prevention program. AB - OBJECTIVE: To assess the outcome of infants born to hepatitis B surface antigen (HBsAg)-positive mothers who received prenatal and infant care in a large, public health care system. DESIGN: Follow-up of a cohort of infants born to HBsAg positive mothers. SETTING: Large, urban hospital providing prenatal care and obstetric services to county health departments. PARTICIPANTS: Forty-two infants born to HBsAg-positive women. INTERVENTIONS: Prenatal testing of women and immunoprophylaxis of infants with hepatitis B immune globulin at birth and hepatitis B vaccine at birth and ages 1 and 6 months. RESULTS: All 42 infants received hepatitis B immune globulin and the first dose of vaccine. Of forty-one infants (98%) who received the second dose of vaccine, 37 received it by age 4 months. Thirty-two infants (76%) completed the three-dose vaccine series by age 12 months, and 34 infants (81%) completed the series by age 18 months. The rate of completion of the hepatitis B vaccine series was comparable to that of infants receiving the third dose of diphtheria-pertussis-tetanus vaccine. Of 26 infants who completed the hepatitis B vaccine series and had follow-up serologic testing, 24 (92%) had adequate levels of antibody to HBsAg. Only one infant who did not complete the vaccine series had serologic evidence of hepatitis B virus infection. No infant was HBsAg-positive. CONCLUSIONS: Public programs serving urban populations can effectively deliver hepatitis B immunoprophylaxis to infants born to HBsAg-positive mothers. PMID- 1496945 TI - Cefepime. Pharmacokinetics and clinical response in patients with cystic fibrosis. AB - OBJECTIVE: To measure first-dose and steady-state plasma, urine, and sputum concentrations of cefepime and make preliminary assessments of the clinical efficacy of cefepime in patients with cystic fibrosis. DESIGN: Open noncomparative clinical trial. SETTING: Memorial Miller Children's Hospital of Long Beach, Calif. PARTICIPANTS: Twelve patients, aged 4 to 41 years, with a confirmed diagnosis of cystic fibrosis and chronic bronchopulmonary infections. INTERVENTIONS: Patients received cefepime at 50 mg/kg per dose (maximum dose, 2 g per dose) given intravenously every 8 hours. Clinical evaluations, pulmonary function tests, quantitative sputum cultures, and sensitivity testing were performed before, at the end of, and 2 weeks after therapy. MEASUREMENTS AND MAIN RESULTS: Mean (+/- SD) peak plasma concentrations after the first dose were 148.2 (36.6) mg/L; the following other values were included: half-life, 1.59 (0.46) hours; area under the curve, 292 (94) microgram/h per milliliter; total-body clearance, 3.01 (1.46) mL/min per kilogram; volume of distribution at steady state, 0.32 (0.10) L/kg; and percent of dose recovered in urine, 52% (27%). Steady-state and first-dose values were similar. Trough levels varied from 6.4 to 7.2 mg/L. Mean (+/- SD) sputum concentrations at steady state varied from 6.3 (5.4) to 4.8 (2.3) mg/L. At completion of therapy, nine of 10 patients' conditions were improved as indicated by clinical scores (greater than 10 points), forced vital capacity (greater than 10%), and a greater than or equal to 1 log decrease in sputum bacterial concentration. Cefepime was well tolerated in 10 patients, but rash and light-headedness developed in two patients. Pseudomonas aeruginosa minimum inhibitory concentration90 increased from the start (64 mg/L) to the end of therapy (256 mg/L) and was unchanged 2 weeks later. CONCLUSION: Based on these data and the potential advantage of a single agent for the treatment of mixed infections (Staphylococcus aureus and P aeruginosa), comparative clinical trials of cefepime and standard therapy for bronchopulmonary exacerbations in patients with cystic fibrosis appear to be warranted. PMID- 1496946 TI - Iron state in female adolescents. AB - OBJECTIVE: To document a subjective response to iron therapy in female adolescents. DESIGN: Double-blind, placebo-controlled prospective study. SETTING: High school classes in an urban community in Israel. PARTICIPANTS: Twenty-nine girls, aged 16 and 17 years, who ingested syrup containing iron (daily for 2 months) and 30 girls who received a placebo. MAIN RESULTS: By the end of the study, a statistically significant improvement in three subjective parameters, ie, lassitude, the ability to concentrate in school, and mood was reported by the girls who ingested iron compared with the controls. Sixty-five percent, 100%, and 65% of the girls, respectively, who reported improvement in the above-mentioned parameters were hypoferremic initially and became normoferremic by the end of the study. CONCLUSION: Iron supplementation may be of benefit to female adolescents, as evidenced by their responses to subjective parameters. PMID- 1496947 TI - Interrupted care. The effects of paging on pediatric resident activities. AB - OBJECTIVE: To determine the content and urgency of pages and their effect on the activities of pediatric residents. DESIGN: Prospective survey. SETTING: University-affiliated teaching hospital. PARTICIPANTS: Seventeen pediatric residents on regular pediatric services. INTERVENTIONS: None. MEASUREMENTS/MAIN RESULTS: On daily logs, interns recorded the activity interrupted by a page and rated the urgency and importance of the page. Almost half of all pages interrupted patient care activities, and 24% interrupted scheduled work rounds or teaching conferences. Interns reported that 34% of pages resulted in a change in patient treatment, but they rated 25% of all pages as unimportant. CONCLUSIONS: "Beepers" frequently interrupt pediatric residents involved in patient care activities and scheduled educational conferences. Studies of interventions aimed at decreasing unnecessary interruptions by pages are needed. PMID- 1496948 TI - Sonography of multinodular thyroid gland in children and adolescents. AB - Multinodular disease of the thyroid gland is uncommon in children and adolescents, and has received little attention in the recent literature. This article reviews the clinical, sonographic, and pathologic findings in 16 children with multinodular disease of the thyroid gland, and draws attention to the high incidence of other associated clinical findings. This condition was associated with a triad including renal and digital anomalies in three patients, with McCune Albright syndrome in two patients, with Hashimoto's thyroiditis in three patients, and with thyroid carcinoma in four patients. Three of five patients with a history of previous radiation therapy had thyroid carcinoma. Sonography is a proven valuable imaging modality for the study of thyroid disease in children and has contributed to our understanding of multinodular disease of the thyroid gland in this age group. PMID- 1496950 TI - Adolescent body image and attitudes to anabolic steroid use. AB - Eleventh-grade students at seven high schools in central Arkansas were surveyed regarding anabolic steroid use, risk-taking behavior, satisfaction with body image, and attitudes and beliefs regarding anabolic steroids. A total of 1492 adolescents were surveyed. Fifty-one (7.6%) of 672 males and 12 (1.5%) of 806 females admitted anabolic steroid use. Fourteen students did not specify gender. Bivariate comparisons showed significant differences between users and nonusers in risk-taking behaviors and degree of satisfaction with body image and muscles. Users were more likely than nonusers to approve of anabolic steroid use in sports and to believe that anabolic steroid use could improve one's health. Multivariate analyses found gender, knowledge of beneficial side effects, knowing other anabolic steroid users, age, and race to be significantly related to anabolic steroid use. Information about steroids' effects seldom came from physicians, but often came from peers. Anabolic steroid use was strongly motivated by social influences, some knowledge of beneficial effects, and denial of adverse effects in white adolescent males in our study population. PMID- 1496949 TI - Growth hormone therapy in Turner's syndrome. Impact of injection frequency and initial bone age. AB - STUDY OBJECTIVE: To determine the influence of the injection frequency and the initial bone age on the efficacy of treatment with biosynthetic growth hormone in Turner's syndrome. DESIGN: Randomized study. SETTING: Referral-based pediatric endocrinology departments of seven university medical centers. PATIENTS: Fifty two patients with Turner's syndrome confirmed with chromosomal analysis. TREATMENT: Somatotropin recombinant DNA (24 IU/m2 of body surface area) subcutaneously administered in three or six injections per week for 2 years. Patients who were older than 12 years at the beginning of the study received low doses of estrogen. RESULTS: The following statistically significant findings supported the use of six injections per week compared with three injections per week: the mean (+/- SD) increment in height during 2 years was 11.3 cm (3.8 cm) with six injections vs 8.6 cm (3.4 cm) with three injections; the increment in height standard deviation score was 0.9 cm (0.5 cm) vs 0.6 cm (0.3 cm); the growth velocity was 6.6 cm/y (2.0 cm/y) vs 5.2 cm/y (1.7 cm/y) in year 1 and 4.7 cm/y (2.0 cm/y) vs 3.4 cm/y (1.7 cm/y) in year 2; and the increment in height standard deviation score for bone age was 0.8 cm (0.5 cm) vs 0.4 cm (0.6 cm). For patients whose initial bone age was more than 13 years, growth velocity increased by 1 to 2 cm in year 1; in year 2 no increment was observed. We did not observe adverse effects. CONCLUSIONS: Biosynthetic growth hormone in a higher-frequency regimen in Turner's syndrome is more efficient in terms of increment in height, growth velocity, and height standard deviation score for bone age than treatment in a lower-frequency regimen. In patients with an initial bone age of more than 13 years, the response was poor. Longer follow-up is necessary to assess the effect on final height. PMID- 1496951 TI - Radiological case of the month. Retrocardiac pneumomediastinum. PMID- 1496952 TI - Radiological case of the month. Unrecognized subaponeurotic hemorrhage. PMID- 1496953 TI - Picture of the month. Occult spinal dysraphism. PMID- 1496954 TI - Pathological case of the month. Alveolar soft-part sarcoma. PMID- 1496955 TI - The prophylactic value of clean intermittent catheterization and anticholinergic medication in newborns and infants with myelodysplasia at risk of developing urinary tract deterioration. AB - OBJECTIVE: To determine if prophylactic use of clean intermittent catheterization and oxybutynin chloride is effective in preventing urinary tract deterioration in myelodysplastic children with high bladder pressure and detrusor-sphincter dyssynergia. DESIGN: Sequential, nonrandomized trial. SETTING: Referral-based urodynamics facility and myelodysplasia program at a major city pediatric hospital. PARTICIPANTS: Twenty-six of 71 consecutive newborns with myelodysplasia who exhibited these urodynamic findings were treated prophylactically over 5 years, whereas 56 of 105 consecutive newborns with the same findings treated during the previous 7 years were treated expectantly. INTERVENTION: Clean intermittent catheterization and oxybutynin therapy were begun when these specific urodynamic findings were detected. MEASUREMENTS AND RESULTS: Follow-up urodynamic studies and roentgenographic assessment of the urinary tract were performed periodically over 5 years. Oxybutynin eliminated uninhibited contractions in two of 14 newborns and lowered peak contractile pressure in the remaining 12. Oxybutynin also lowered bladder-filling pressure at capacity in all 12 additional neonates with only hypertonicity. Twenty-four (92%) of 26 children had normal kidney function and drainage during the observation period, two (8%) developed hydroureteronephrosis, and one of these two had vesicoureteral reflux. In a prior study of children similarly at risk who were treated expectantly, the roentgenographic appearance of the upper urinary tract had changed in 48%. Minimal side effects were noted with oxybutynin, and no adverse effects of clean intermittent catheterization were detected. CONCLUSIONS: Oxybutynin effectively reduces uninhibited contractions and lowers detrusor filling pressure, while clean intermittent catheterization allows bladder emptying at low pressures with no measurable side effects in these neonates. The overall effect maintains the integrity of the upper urinary tract in almost all myelodysplastic children at risk of urinary tract deterioration. Expectant therapy can no longer be advocated when these "at risk" children are identified because prophylactic treatment is so effective. PMID- 1496956 TI - Tinea pedis in children. AB - OBJECTIVE: To demonstrate that tinea pedis should be considered in the differential diagnosis of children with foot dermatitis. DESIGN: Patient series. SETTING: Outpatient dermatology practice at the Children's Hospital of Pittsburgh (Pa). PARTICIPANTS: Children with culture-proven tinea pedis from 1987 until 1990. MEASUREMENTS/MAIN RESULTS: Fungal cultures were used to identify 13 girls and 13 boys ranging in age from 17 months to 18 years with tinea pedis. A parent was the probable source of infection in at least 25% of cases. CONCLUSIONS: Tinea pedis is not a rare occurrence in children and should be considered in any patient with a foot rash. PMID- 1496957 TI - Establishing standards of orthostatic measurements in normovolemic adolescents. AB - OBJECTIVE: To determine normal orthostatic heart rate and blood pressure changes in healthy adolescents. DESIGN: Survey. SETTING: General adolescent clinic at a military teaching medical center in Honolulu, Hawaii. PARTICIPANTS: One hundred healthy normovolemic patients aged 12 to 19 years representing a cross section of individuals from a diverse military population during a 5-month study period. SELECTION PROCEDURE: Convenience sample. INTERVENTIONS: None. MEASUREMENTS/MAIN RESULTS: The mean (+/- 2 SDs) orthostatic heart rate change in beats per minute was 21.5 +/- 21.2, with a range of 50 to -3 beats per minute. The mean (+/- 2 SDs) systolic blood pressure change was -0.9 +/- 15.7 mm Hg, with a range of 19 to -17 mm Hg. Orthostatic measurements in a normal adolescent population may result in a heart rate increase of 40 to 50 beats per minute and a systolic blood pressure decrease of 15 mm Hg. There were no significant differences between individuals with respect to age, race, sex, and body habitus. CONCLUSIONS: Healthy adolescents display wide variation in orthostatic measurements that exceed previously accepted standards. Further study is required to determine if sensitivity and specificity values exist for orthostatic measurements that can identify individuals with intravascular volume depletion. PMID- 1496958 TI - Neonatal morphometry. Relation to obstetric, pediatric, and menstrual estimates of gestational age. AB - OBJECTIVE: To determine gestational age-dependent neonatal morphometrics based on last menstrual periods (LMPs), Ballard examinations, and obstetric estimates of gestational age. DESIGN, SETTING, AND PARTICIPANTS: Cross-sectional survey of 38,818 live-born neonates at a tertiary care center in Detroit, Mich. SELECTION PROCEDURES: Consecutive sample of all viable, structurally normal, singleton neonates delivered at Hutzel Hospital from 1984 through 1991. MEASUREMENTS/MAIN RESULTS: Neonatal weights, lengths, and head circumferences were recorded at birth. Gestational age-dependent morphometrics were based solely on LMPs and compared with those based on obstetric estimates (using LMPs corrected by fetal ultrasound). Ballard examination had an 85.4% concurrence (within 14 days) with obstetric estimates of gestational age, but only a 69.9% (P less than .0001) agreement with LMP. Dating only by LMP significantly overestimated the prevalence of prematurity (odds ratio [OR], 1.3; 99% confidence interval [CI], 1.3 to 1.4) and postmaturity (OR, 5.0; 99% CI, 4.6 to 5.4), distorting apparent growth patterns, especially for preterm neonates. In contrast to previous studies based solely on LMPs, morphometric measurements increased beyond 40 weeks when dated by obstetric estimates. CONCLUSIONS: Gestational age-dependent neonatal morphometrics should not be based solely on LMPs. PMID- 1496960 TI - Triplets and higher-order multiple births. Time trends and infant mortality. AB - OBJECTIVES: To describe changes in rates of higher-order multiple births (triplets and higher) between 1972 and 1989, to compare infant mortality rates in infants of higher-order multiple births and singletons born from 1983 through 1985, and to compare infant mortality rates among higher-order multiples born from 1983 through 1985 with rates among those born in 1960. RESEARCH DESIGN: Population-based analysis of live births (1972 through 1989) and infant deaths (1960 and 1983 through 1985) in the United States. The rate of higher-order multiple births was calculated per 100,000 live births. DATA SOURCE: Computerized national natality files for 1972 through 1989 and national linked birth/infant death data sets for 1960 and 1983 through 1985 from the National Center for Health Statistics, Centers for Disease Control. POPULATION: Live births to white and black women in the United States. INTERVENTIONS: None. MAIN RESULTS: Between 1972 through 1974 and 1985 through 1989 the rate of higher-order multiple births increased by 113% among infants of white mothers and by 22% among infants of black mothers. In whites the increase was mostly age specific and was not due to the upward shift in the maternal age distribution. The increase was particularly large in white women aged 30 through 34 years (152%) and 35 through 39 years (165%) and in more highly educated mothers. In blacks the modest increase in the rate of higher-order multiple births was mostly due to an upward shift in the maternal age distribution. From 1983 through 1985, mortality of infants of higher order multiple births was about 15 times that of singletons. This was due almost entirely to the lower birth weight distribution of infants of higher-order multiple births. Their weight-specific mortality compared favorably with that of singletons. At 500 through 999 g, mortality was about the same. In weight categories between 1000 and 1999 g, mortality rates in higher-order multiple births were much lower: weight-specific relative risks ranged from 0.30 to 0.73. Between 1960 and 1983 through 1985 infant mortality in higher-order multiple births declined by about 50%. CONCLUSIONS: It is likely that much of the increase in the incidence of higher-order multiple births is due to the rise in the use of ovulation-inducing drugs for the treatment of infertility. This increase and the decline in mortality risk have created a much greater need for medical and social services for infants of higher-order multiple births and their families. PMID- 1496959 TI - The changing epidemiology of neural tube defects. United States, 1968-1989. AB - OBJECTIVE: To describe the recent trends and epidemiologic characteristics of neural tube defects in the United States. RESEARCH DESIGN: Ongoing surveillance data. SETTING: Two birth defect surveillance systems: the nationwide Birth Defects Monitoring Program and the Metropolitan Atlanta (Ga) Congenital Defects Program for 1970 through 1989 and 1968 through 1989, respectively. PARTICIPANTS: Between 1970 and 1989, using discharge diagnoses of approximately 1 million live born and stillborn infants per year, the Birth Defects Monitoring Program identified 15,503 cases of spina bifida and anencephaly. Between 1968 and 1989, using discharge diagnoses and clinical records until age 1 year of 38,000 infants per year, the Metropolitan Atlanta Congenital Defects Program identified 800 cases of spina bifida and anencephaly. INTERVENTIONS: None. MEASUREMENTS/MAIN RESULTS: Nationwide, neural tube defect rates have declined from 1.3 per 1000 births in 1970 to 0.6 per 1000 births in 1989. In Atlanta, neural tube defect rates have declined from 2.0 per 1000 births in 1968 to 0.6 per 1000 births in 1989. Several changes in the epidemiologic characteristics of neural tube defects were observed: (1) the proportion of spina bifida cases has increased; (2) the proportion of neural tube defect cases compared with the proportion of other unrelated defects has increased; (3) the race ratio of whites to other races for isolated neural tube defect cases has declined in Atlanta; and (4) the rate of isolated neural tube defects in females has also decreased. CONCLUSIONS: The declining rates of neural tube defects can be partially explained by increased widespread prenatal diagnostic techniques, strongly suggesting the role of environmental factors in neural tube defects. In particular, the use of multivitamins and folic acid to prevent the occurrence of neural tube defects needs further evaluation. Nevertheless, the changing clinical and epidemiologic characteristics of cases over time points to the etiologic heterogeneity of these conditions. PMID- 1496961 TI - The pediatrician's role in encouraging parent-child communication about the acquired immunodeficiency syndrome. AB - OBJECTIVE: We explored whether communication from pediatrician to parent to child might assist in education about and prevention of human immunodeficiency virus (HIV) infection by comparing parents of children aged 10 through 17 years who did discuss acquired immunodeficiency syndrome (AIDS) with their children with parents of children aged 10 through 17 years who did not discuss AIDS with their children. RESEARCH DESIGN: Secondary analyses of the National Health Interview Survey, a general population survey with items on AIDS. We compared the relative importance of various characteristics in distinguishing parents who did discuss AIDS from those who did not. Variables included whether the parents had received an informational brochure about AIDS from a health care provider. RESULTS: Twenty percent of respondents had at least one child between ages 10 and 17 years; 62% of these parents had discussed AIDS with their children. This percentage was greater for parents living in metropolitan statistical areas with fewer than 100,000 persons compared with parents living in larger cities (73.6% vs 62.7%). Seventy-four percent of women (n = 4745) had spoken to their children about AIDS; only 49% of men (n = 3271) had done so. This gender difference was present in both one- and two-parent households. Hispanics were significantly less likely than non-Hispanics to have discussed AIDS with their children (men, 38.9% vs 49.9%; women, 62.6% vs 74.2%). Gender by far was most strongly associated with talking to children about AIDS, followed by self-assessed knowledge, knowing someone infected with the HIV, and actual knowledge about HIV and AIDS. Parents who reported reading an AIDS-related brochure were significantly more likely to have spoken with their children than were parents who had not read such a brochure (76.2% vs 57.4%). Thirty-seven percent of parents receiving a brochure received one from a health care provider. CONCLUSIONS: Pediatricians can assist in efforts to prevent HIV infection and AIDS by educating parents, especially mothers, about AIDS; by providing them with well-designed brochures about AIDS; and by encouraging them to discuss HIV with their children in a developmentally appropriate manner. PMID- 1496962 TI - Screening for maternal depression in pediatric clinics. AB - OBJECTIVE: The purpose of this study was to assess the frequency of and risk factors for depressive disorders among mothers of young children and to compare the eight-item RAND screening instrument for depressive disorders with an easily scored three-item version of the test. DESIGN: A cross-sectional survey. SETTING: Five pediatric clinics in the Seattle-Tacoma, Washington area, two private practices, two university-affiliated teaching clinics, and the Madigan Army Medical Center pediatric clinic. PARTICIPANTS: Convenience sample of 667 English speaking mothers who completed the depression items on an anonymous self administered questionnaire on family health. INTERVENTIONS: None. MEASUREMENTS AND RESULTS: The results of women surveyed showed that 19% were positive for depression on the RAND instrument. Women whose survey results were positive were younger (28.2 vs 30.3 years of age), had less education (12.9 vs 14.4 years), and had lower monthly incomes ($1803 vs $2923) than those who results were not positive. Positive scores were more common among women surveyed in teaching clinics (20%) and military clinics (24%) than among women surveyed in private practices (12%), among single vs married mothers (32% vs 15%), among nonwhites vs whites (29% vs 16%), and among those with positive screening test results for drugs compared with those with negative screening test results (45% vs 17%) (P less than .01 for all comparisons). Compared with the eight-item instrument, the three-item version had a sensitivity of 100%, a specificity of 88%, and a positive predictive value of 66%. CONCLUSIONS: Depression is common among mothers of young children. The three-item version compares favorably with the eight-item RAND screening instrument for depressive disorders. PMID- 1496963 TI - Adequacy of hemodialysis. AB - Despite technical advances in the delivery of hemodialysis over the past decade, the mortality rate of hemodialysis-dependent, end-stage renal disease (ESRD) patients in the United States remains high. The increase in the number and severity of comorbid conditions of patients entering ESRD is a factor contributing to this high mortality. Nevertheless, there is increasing evidence that the dose of dialysis received by US patients is inadequate and that this plays a major role in the observed high mortality. In this review, we examine some of the parameters used to judge the adequacy of dialysis, as well as factors that can result in differences between prescribed and delivered dose of hemodialysis. Based on available evidence, we propose that for most patients the optimum dose of dialysis, above which further improvement of morbidity and mortality is doubtful, is represented by a delivered dose of dialysis equivalent to a Kt/V of 1.4 or greater, using biocompatible membranes. The prescription of this optimal dose of dialysis must be coupled with an ongoing effort to monitor delivery of the appropriate dose. PMID- 1496964 TI - Blood pressure related separately to parenchymal fibrosis and vasculopathy of the kidney. AB - The term nephrosclerosis is customarily used to designate a pathological entity that tends to characterize subjects with high blood pressure; it refers to a condition of diffuse fibrous replacement of renal substance secondary to ischemia from hypertension-related vascular injury. The features of parenchymal fibrosis can be distinguished from those of vasculopathies in tissue sections, parenchymal fibrosis being measured by assessing the degree of interstitial fibrosis and by counting obsolete glomeruli, while vasculopathies are measured by determining arterial intimal fibroplasia and by counting hyalinized arterioles. A series of 166 autopsies in subjects aged 25 to 92 years, selected because ample documentation of blood pressure was available, was assessed. One form of vasculopathy, arterial fibroplasia, is a better correlate of high blood pressure than is parenchymal fibrosis in this body of data. Cases with much vasculopathy and little parenchymal fibrosis occurred frequently, and these subjects were usually hypertensive. Cases with little vasculopathy and much parenchymal fibrosis were also encountered, but these subjects were usually not hypertensive. The suggested conclusion is that blood pressure relates less to the renoprival state of nephron loss than it does to renal ischemia in patients with nephrosclerosis. PMID- 1496965 TI - Effect of nifedipine and captopril on glomerular hyperfiltration in normotensive man. AB - Glomerular hyperfiltration and hypertension induced by extensive loss of renal parenchyma are suspected to accelerate progression of renal failure. Amino acid infusion or protein ingestion also modify renal hemodynamics and increase glomerular filtration rate (GFR). This phenomenon was used to study the influence of two commonly used antihypertensive agents, captopril and nifedipine, on renal hemodynamics at rest and during glomerular hyperfiltration. Thirteen healthy volunteers were studied on three separate days (days A, B, and C) in random sequence: inulin and p-amino hippurate (PAH) clearance were measured first under glucose infusion and afterwards under stimulation by amino acid infusion (0.35 mmol/kg/min; 4 mg/kg/min). Day A served as a control, where no medication was given. On day B, 10 mg nifedipine, and on day C, 25 mg captopril, were administered orally before study. Without premedication (= day A, control) GFR increased from 108.0 +/- 6.9 mL/min (SEM) to 131.7 +/- 7.0 mL/min (P less than 0.05). On day B (nifedipine), GFR before stimulation by amino acids was already elevated to 121.8 +/- 4.2 mL/min (P less than 0.05 compared with day A) and increased to 132.6 +/- 6.3 mL/min with infusion of amino acids, thus to the same range as on day A without medication. On day C, after captopril, GFR did not increase with infusion of amino acids (from 112.5 +/- 7.2 to 117.3 +/- 6.3 mL/min). Our results indicate the calcium channel antagonist nifedipine and the angiotensin-converting enzyme (ACE) inhibitor captopril differ in their effect on intrarenal hemodynamic parameters. Nifedipine induces hyperfiltration at rest and allows maximal hyperfiltration to develop under amino acid infusion.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1496966 TI - Clinical profiles of gross hematuria in autosomal dominant polycystic kidney disease. AB - There is little information on the characteristics, management, or sequelae of gross hematuria in autosomal dominant polycystic kidney disease (ADPKD). Therefore, we obtained detailed information regarding gross hematuria in 191 adult ADPKD subjects. Forty-two percent (N = 81) experienced at least one episode of gross hematuria. The mean age of the initial episode was 30 +/- 1 years; only 10% of subjects reported the first episode before age 16. Twenty-three percent of those with gross hematuria had experienced more than six occurrences. Sixty-two percent of patients with bleeding indicated a presumptive precipitating event, most commonly urinary tract infection (42% overall, 61% of females v 17% of males, P less than 0.01), or sports or strenuous activity (20% of males v 11% of females, NS). In 56% of subjects, the episode persisted for 2 to 7 days. Hypertensive ADPKD subjects were more likely to have gross hematuria than normotensive subjects (48% v 30%, P less than 0.02) and those with gross hematuria had larger renal size (820 +/- 87 v 588 +/- 52 cm3, P less than 0.03). Moreover, those subjects with more episodes of gross hematuria had a higher serum creatinine concentration than those with fewer episodes (serum creatinine: 0 episodes, 120 +/- 10 v greater than 5 episodes, 190 +/- 30 mumol/L, P less than 0.04 [1.4 +/- 0.1 v 2.1 +/- 0.3 mg/dL]). This association suggests that, although self-limited, cumulative episodes of gross hematuria may have an unfavorable impact on long-term renal function. PMID- 1496967 TI - Renal prostacyclin biosynthesis is reduced in children with hemolytic-uremic syndrome in the context of systemic platelet activation. AB - Previous studies have reported various abnormalities in prostacyclin (PGI2) synthesis and metabolism in hemolytic-uremic syndrome (HUS). However, the conclusions of most of these studies are based on in vitro or ex vivo experiments that only give an indirect estimate of the actual biosynthesis in vivo. We studied the urinary excretion of PGI2 metabolites, taken as a marker of the actual biosynthesis, in six children with HUS during the acute phase of the disease and again when remission was achieved. Eight age- and sex-matched healthy children were studied as controls. Since HUS is also associated with platelet activation and consumption, we also studied the urinary excretion of thromboxane A2 (TxA2) metabolites. Urinary PGI2 and TxA2 metabolites were assessed by radioimmunoassay after high-performance liquid chromatography (HPLC) purification. Urinary excretion of the PGI2 hydrolysis product, 6-keto-PGF1 alpha, was significantly reduced in children with acute HUS as compared with controls, indicating a defective renal synthesis of PGI2. A significant inverse correlation was found between urinary 6-keto-PGF1 alpha and blood urea nitrogen (BUN), as well as plasma creatinine. At remission, urinary 6-keto-PGF1 alpha levels increased to values higher than those of controls. By contrast, the urinary excretion of the major PGI2 beta-oxidation product, 2,3-dinor-6-keto-PGF1 alpha, was comparable to controls, indicating normal systemic PGI2 biosynthesis. The urinary excretion of both TxA2 hydrolysis product, TxB2, and the major beta oxidation metabolite, 2,3-dinor-TxB2, were lower than normal in the acute phase of HUS if expressed as absolute values.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1496968 TI - Renal thrombotic microangiopathy in patients with systemic lupus erythematosus and the antiphospholipid syndrome. AB - Current studies indicate that a thrombotic microangiopathy (TMA) identifies patients with systemic lupus erythematosus (SLE) who are at high risk of progressing to end-stage renal disease. We have observed two patients with SLE and one patient with a primary antiphospholipid syndrome (APS) who developed acute renal insufficiency with thrombocytopenia. Renal biopsies showed a TMA characterized by thrombi or by cellular and mucoid intimal hyperplasia of small arteries and arterioles. No arterial or arteriolar immune-complex deposits were detected by immunofluorescent or electron microscopy. Biopsies from one SLE patient and the APS patient showed no immune-complex glomerular disease. Both had serum antiphospholipid antibodies (aPL). aPL were not detected in the serum of the other SLE patient who had an active lupus nephritis. Acute renal failure and thrombocytopenia resolved in each case following treatment by plasmapheresis or prednisone and heparin. None of the patients were initially treated with cytotoxic drugs. As more knowledge is gained, the accurate identification of renal vascular lesions in SLE or related diseases could influence renal prognosis and choice of therapy. The cases reported here provide further evidence that a TMA can cause acute renal failure independent of lupus nephritis. TMA should be distinguished from other forms of renal vascular disease, particularly a noninflammatory lupus microangiopathy, which is probably mediated by subendothelial immune-complex deposits. The absence of immunoglobulin deposits in vessels involved by a TMA indicates that microvascular thrombosis is promoted by mechanisms other than those usually attributed to immune-complex disease. Phospholipid reactive antibodies may be pathogenetic in some cases. PMID- 1496969 TI - Intestinal necrosis associated with postoperative orally administered sodium polystyrene sulfonate in sorbitol. AB - We estimated the incidence of intestinal necrosis in 752 hospitalized patients who had received sodium polystyrene sulfonate (SPS). Of these 752 patients, 117 were exposed within 1 week of surgery. Two cases of intestinal necrosis were discovered, both in patients who had received orally administered SPS in sorbitol within 1 week of surgery. Based on these two cases, the postoperative incidence of intestinal necrosis associated with SPS was 1.8%. For comparative purposes, we identified 862 patients who had undergone hemodialysis, renal transplantation, or cardiac transplantation, but did not receive SPS. No cases of idiopathic intestinal necrosis were found in this second group (P = 0.014). These data suggest that SPS in sorbitol-associated intestinal complications may be a relatively common occurrence in postoperatively exposed patients. PMID- 1496970 TI - Cyclosporine nephropathy: morphometric analysis of the medullary thick ascending limb. AB - The effects of cyclosporine A (CsA) (12.5 mg/kg/d) on the medullary thick ascending limb (mTAL) were studied in five experimental groups: vehicle-treated control (C), salt depletion (SD), cyclosporine (CsA), and the combination of both salt depletion and cyclosporine for 3 (CsA-SD:S) and 8 (CsA-SD:L) weeks. Evaluation was performed on 1-micron plastic horizontal sections. mTALs were classified as either atrophic or nonatrophic by assessing mitochondrial density. The mean cross-sectional area of atrophic mTALs was found to be significantly smaller than the mean of nonatrophic mTALs in all treatment groups. The percentage of atrophic tubules was found to be significantly increased in both CsA-SD groups as compared with the other three treatment groups (P less than 0.01). Regression analysis indicated a rectangular hyperbolic relationship between the percentage of atrophic tubules and mean nonatrophic tubule cross sectional area (P less than 0.0001). Thus, low levels of injury are associated with a rapid increase in cross-sectional tubular area (hypertrophy), and this response plateaued with increasing degrees of injury. Terminal plasma creatinine correlated with nonatrophic tubular cross-section area (r = 0.52, P less than 0.003). These studies indicate that CsA induces mTAL atrophy, which is more extensive with salt depletion. With limited injury, hypertrophy develops. However, the hypertrophic response cannot be sustained with increasing degrees of injury. The phenomenon of mTAL atrophy and hypertrophy is particularly important, since hypertrophy itself is a known risk factor for mTAL injury. PMID- 1496971 TI - Dietary supplementation with L-arginine ameliorates the progression of renal disease in rats with subtotal nephrectomy. AB - We studied the effect of dietary supplementation with L-arginine for 6 weeks on the progression of renal disease in female Sprague-Dawley rats subjected to sham operation (groups 1 and 2) or surgical ablation of 85% to 90% of the total renal mass (groups 3 and 4). All rats were fed a standard rat chow containing 22.8% protein. Rats in groups 1 (n = 5) and 3 (n = 9) served as controls and drank tap water ad libitum. Rats in groups 2 (n = 6) and 4 (n = 6) drank tap water supplemented with 1% L-arginine. Rats in groups 1 and 2 had similar values for glomerular and tubular function and serum chemistries 6 weeks after sham operation. Sham-operated rats given L-arginine had significantly greater urine urea excretion than similar rats drinking tap water. Rats with subtotal nephrectomy (groups 3 and 4) had a significantly higher blood pressure, greater proteinuria, and a significantly lower plasma albumin than sham-operated rats (groups 1 and 2). Rats with remnant kidneys given 1% L-arginine (group 4) had significantly greater values for glomerular filtration rate (GFR) and P-amino hippurate (PAH) clearance than similar rats given tap water (group 3), despite comparable levels of systemic blood pressure, hematocrit, body weight, plasma chemistries, including L-arginine, and urine chemistries, except urea excretion. The remnant kidney of rats given L-arginine (group 4) had a greater number of normal or minimally abnormal glomeruli and fewer interstitial changes than that of rats given tap water (group 3).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1496972 TI - Decline in creatinine clearance in a patient with glomerulomegaly associated with a congenital cyanotic heart disease. AB - Glomerulomegaly is associated with congenital cyanotic heart disease and has heretofore been considered a benign condition. We describe a patient with congenital cyanotic heart disease and glomerulomegaly. Deterioration of renal function was demonstrated by comparison of creatinine clearances measured at the time of kidney biopsy and 4 years later. No alteration in kidney histology other than glomerulomegaly and focal glomerulosclerosis at autopsy could account for this deterioration. This is the first description of deterioration of renal function in a patient with glomerulomegaly and congenital cyanotic heart disease. This observation may influence the management of patients with glomerulomegaly and congenital cyanotic heart disease who are potential recipients of heart or heart-lung allografts. PMID- 1496973 TI - Renal autotransplantation in the loin pain-hematuria syndrome: a cautionary note. AB - The current literature suggests that renal autotransplantation is nearly uniformly effective in controlling the severe and debilitating pain of the loin pain-hematuria syndrome (LPHS). However, we report two patients thought to have this syndrome in whom renal autotransplantation did not result in long-term control of pain. In case 1, autotransplantation resulted in immediate cessation of pain; however, the flank pain recurred 7 1/2 months later. The recurrent pain was also severe and debilitating, requiring narcotic medications for control. In case 2, autotransplantation of the left kidney resulted in chronic pain in the left pelvic area, the site of the autotransplanted kidney. In addition, the patient continued to experience chronic discomfort in the left flank and along the flank incision. One year after autotransplantation, the patient still requires multiple daily doses of narcotic medications for pain control. Our two patients represent the 13th and 14th reported patients subjected to renal autotransplantation for management of LPHS. They represent only the third and fourth reported patients with recurrence of pain after renal autotransplantation. Because studies with negative results are less likely to be reported in the literature than studies with positive results, it is possible that the literature overestimates the effectiveness of renal autotransplantation in the LPHS. To assess the true effectiveness of renal autotransplantation in LPHS, a survey of patients with LPHS who have undergone renal autotransplantation needs to be performed. PMID- 1496974 TI - Reversible renal failure due to IgA nephropathy associated with osteomyelitis. AB - Clinical features of acute glomerulonephritis, with microscopic hematuria, red blood cell (RBC) casts, proteinuria, and acute renal insufficiency developed in a patient with chronic osteomyelitis. Before the development of osteomyelitis, renal function and findings on urinalysis were normal. Complete eradication of osteomyelitis by surgical amputation led to resolution of the abnormal urinary findings, and renal function returned to near pre-osteomyelitis levels. Although acute glomerular disease has been reported to occur as a rare complication of osteomyelitis, the unique feature of the present case was the histological finding of IgA nephropathy. There was no arthritis, purpura, skin rash, or gastrointestinal involvement to suggest a diagnosis of Henoch-Schonlein purpura and there was no evidence of chronic liver disease. The temporal relationship between the onset of the renal disease, which followed the development of chronic osteomyelitis, and its resolution following removal of the focus of infection, suggests that the IgA nephropathy may have been related directly to the osteomyelitis (secondary IgA nephropathy). Glomerular diseases associated with chronic bacterial infections, including osteomyelitis, are discussed, with emphasis on infections that have been associated with the development or exacerbation of IgA nephropathy. PMID- 1496975 TI - Acute renal failure in Crohn's disease due to IgA nephropathy. PMID- 1496976 TI - Henoch-Schonlein purpura in a patient with diabetic nephropathy: case report and a review of the literature. PMID- 1496977 TI - Immunotactoid glomerulopathy. PMID- 1496978 TI - Fatal destructive cervical spondyloarthropathy. PMID- 1496979 TI - Can we regulate the quality of care. PMID- 1496980 TI - Minireview: cryptic translocations and telomere integrity. PMID- 1496981 TI - Analysis of chromosome 22 deletions in neurofibromatosis type 2-related tumors. AB - The neurofibromatosis type 2 (NF2) gene has been hypothesized to be a recessive tumor suppressor, with mutations at the same locus on chromosome 22 that lead to NF2 also leading to sporadic tumors of the types seen in NF2. Flanking markers for this gene have previously been defined as D22S1 centromeric and D22S28 telomeric. Identification of subregions of this interval that are consistently rearranged in the NF2-related tumors would aid in better defining the disease locus. To this end, we have compared tumor and constitutional DNAs, isolated from 39 unrelated patients with sporadic and NF2-associated acoustic neuromas, meningiomas, schwannomas, and ependymomas, at eight polymorphic loci on chromosome 22. Two of the tumors studied revealed loss-of-heterozygosity patterns, which is consistent with the presence of chromosome 22 terminal deletions. By using additional polymorphic markers, the terminal deletion breakpoint found in one of the tumors, an acoustic neuroma from an NF2 patient, was mapped within the previously defined NF2 region. The breakpoint occurred between the haplotyped markers D22S41/D22S46 and D22S56. This finding redefines the proximal flanking marker and localizes the NF2 gene between markers D22S41/D22S46 and D22S28. In addition, we identified a sporadic acoustic neuroma that reveals a loss-of-heterozygosity pattern consistent with mitotic recombination or deletion and reduplication, which are mechanisms not previously seen in studies of these tumors. This finding, while inconsistent with models of tumorigenesis that invoke single deletions and their gene-dosage effects, lends further support to the recessive tumor-suppressor model. PMID- 1496983 TI - Substitution of aspartate for glycine 1018 in the type III procollagen (COL3A1) gene causes type IV Ehlers-Danlos syndrome: the mutated allele is present in most blood leukocytes of the asymptomatic and mosaic mother. AB - A proband with arterial ruptures and skin changes characteristic of the type IV variant of Ehlers-Danlos syndrome was found to have a single-base mutation in the type III procollagen gene, which converted the codon for glycine at amino acid position 1018 to a codon for aspartate. (Amino acid positions are numbered by the standard convention in which the first glycine of the triple-helical domain of an alpha chain is number 1. The numbers of positions in the alpha 1(III) chains can be converted to positions in the human pro alpha(III) chain by adding 167.) Nucleotide sequencing of overlapping PCR products in which the two alleles were distinguished demonstrated that the mutation of glycine 1018 was the only mutation that changed the primary structure of type III procollagen. The glycine substitution markedly decreased the amount of type III procollagen secreted into the medium by cultured skin fibroblasts from the proband. It is surprising that the same mutation was found in about 94% of the peripheral blood leukocytes from the proband's asymptomatic 72-year-old mother. Other tissues from the mother contained the mutated allele; it was present in 0%-100% of different samples of hair cells and in about 40% of cells from the oral epithelium. Therefore, the mother was a mosaic for the mutation. Since the mutated allele was present in cells derived from all three germ layers, the results indicated that the mutation arose by the late blastocyst stage of development. The results also indicate that assays of blood leukocytes do not always reveal mosaicism or predict phenotypic involvement of tissues, such as blood vessels, that are derived from the same embryonic cells as are leukocytes. PMID- 1496982 TI - Neurofibromatosis type 2 appears to be a genetically homogeneous disease. AB - Neurofibromatosis type 2 (NF2) is an autosomal dominant syndrome characterized by the development of vestibular schwannomas and other tumors of the nervous system, including cranial and spinal meningiomas, schwannomas, and ependymomas. The presence of bilateral vestibular schwannomas is sufficient for the diagnosis. Skin manifestations are less common than in neurofibromatosis type 1 (NF1; von Recklinghausen disease). The apparent clinical distinction between NF1 and NF2 has been confirmed at the level of the gene locus by linkage studies; the gene for NF1 maps to chromosome 17, whereas the gene for NF2 has been assigned (in a single family) to chromosome 22. To increase the precision of the genetic mapping of NF2 and to determine whether additional susceptibility loci exist, we have performed linkage analysis on 12 families with NF2 by using four polymorphic markers from chromosome 22 and a marker at the NF1 locus on chromosome 17. Our results confirm the assignment of the gene for NF2 to chromosome 22 and do not support the hypothesis of genetic heterogeneity. We believe that chromosome 22 markers can now be used for presymptomatic diagnosis in selected families. The NF2 gene is tightly linked to the D22S32 locus (maximum lod score 4.12; recombination fraction 0). A CA-repeat polymorphism at the CRYB2 locus was the most informative marker in our families (lod score 5.99), but because the observed recombination fraction between NF2 and CRYB2 was 10 cM, predictions using this marker will need to be interpreted with caution. PMID- 1496984 TI - Role of the pseudoautosomal region in sex-chromosome pairing during male meiosis: meiotic studies in a man with a deletion of distal Xp. AB - Meiotic studies were undertaken in a 24-year-old male patient with short stature, chondrodysplasia punctata, ichthyosis, steroid sulfatase deficiency, and mild mental retardation with an inherited cytologically visible deletion of distal Xp. Molecular investigations showed that the pseudoautosomal region as well as the steroid sulfatase gene were deleted, but telomeric sequences were present at the pter on the deleted X chromosome. A complete failure of sex-chromosome pairing was observed in the primary spermatocytes of the patient. Telomeric approaches between the sex chromosomes were made at zygotene in some cells, but no XY synaptonemal complex was formed. The sex chromosomes were present as univalents at metaphase I, and germ-cell development was arrested between metaphase I and metaphase II in the vast majority of cells, consistent with the azoospermia observed in the patient. The failure of XY pairing in this individual indicates that the pseudoautosomal sequences play an important role in initiating XY pairing and formation of synaptonemal complex at meiosis. PMID- 1496985 TI - Ethnic differentiation at VNTR loci, with special reference to forensic applications. AB - Allele-rich VNTR loci provide valuable information for forensic inference. Interpretation of this information is complicated by measurement error, which renders discrete alleles difficult to distinguish. Two methods have been used to circumvent this difficulty--i.e., binning methods and direct evaluation of allele frequencies, the latter achieved by modeling the data as a mixture distribution. We use this modeling approach to estimate the allele frequency distributions for two loci--D17S79 and D2S44--for black, Caucasian, and Hispanic samples from the Lifecodes and FBI data bases. The data bases are differentiated by the restriction enzyme used: PstI (Lifecodes) and HaeIII (FBI). Our results show that alleles common in one ethnic group are almost always common in all ethnic groups, and likewise for rare alleles; this pattern holds for both loci. Gene diversity, or heterozygosity, measured as one minus the sum of the squared allele frequencies, is greater for D2S44 than for D17S79, in both data bases. The average gene diversity across ethnic groups when PstI (HaeIII) is used is .918 (.918) for D17S79 and is .985 (.983) for D2S44. The variance in gene diversity among ethnic groups is greater for D17S79 than for D2S44. The number of alleles, like the gene diversity, is greater for D2S44 than for D17S79. The mean numbers of alleles across ethnic groups, estimated from the PstI (HaeIII) data, are 40.25 (41.5) for D17S79 and 104 (103) for D2S44. The number of alleles is correlated with sample size. We use the estimated allele frequency distributions for each ethnic group to explore the effects of unwittingly mixing populations and thereby violating independence assumptions. We show that, even in extreme cases of mixture, the estimated genotype probabilities are good estimates of the true probabilities, contradicting recent claims. Because the binning methods currently used for forensic inference show even less differentiation among ethnic groups, we conclude that mixture has little or no impact on the use of VNTR loci for forensics. PMID- 1496986 TI - A note on Hardy-Weinberg equilibrium of VNTR data by using the Federal Bureau of Investigation's fixed-bin method. AB - To fully utilize the information of VNTR data for forensic inference, the probability of observing the matching suspect and evidentiary profile in a reference population is estimated, usually by assuming independence of alleles within and between loci. This assumption has been challenged on the basis of the observation that there is frequently an excess of single-band phenotypes (SBP) in forensic data bases, which could indicate lack of independence. Nevertheless, another explanation is that the excess SBP are artifacts of laboratory methods. In this report we examine the excess of SBP for three VNTR loci studied by the FBI (D17S79 and D2S44, for blacks, and D14S13, for Caucasians). The FBI claims that the excess is due to the effect of null alleles; the null alleles are suspected to be too small to be detected. We estimate the frequency of null alleles for two loci (D17S79 and D14S13) by comparing, for these loci, the data from the FBI data base and the data from the Lifecodes data base. These comparisons yield information on small fragments because Lifecodes uses the restriction enzyme PstI, which yields larger fragments than does HaeIII, which the FBI uses. For D17S79 in blacks, we estimate a null allele frequency of 4.4%, and, for D14S13 in Caucasians, we estimate a frequency of 3.0%. The null-allele frequency for D2S44 in blacks is derived similarly, again being based on analyses of DNA cut with HaeIII and PstI; our estimate of the null-allele frequency for this locus is 1.5%.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1496987 TI - Likelihoods of multilocus DNA fingerprints in extended families. AB - A concept for the application of complex pedigree analysis to multilocus DNA fingerprinting is described. By following this approach, the extent to which the DNA fingerprints of grandparents influence the phenotype likelihoods of their offspring was determined. It was demonstrated by simulation that approximately 90% of paternity disputes can be solved if mother, child, and paternal grandparents, instead of the putative father, are tested. If only phenotype information on a single paternal sib is allowed for, true paternity will be detected with reasonable persuasive power in up to 64% of cases. Exclusion of false paternity remains possible for 40% of cases. Finally, the analysis concept is modified by reducing the number of genotype variations considered in likelihood computations. This time-saving procedure is shown to yield sufficiently accurate likelihoods in the analysis of both simulation data and multilocus DNA fingerprints obtained in two large families. PMID- 1496988 TI - Dystrophin in frameshift deletion patients with Becker muscular dystrophy. AB - In a previous study we identified 14 cases with Duchenne muscular dystrophy (DMD) or its milder variant, Becker muscular dystrophy (BMD), with a deletion of exons 3-7, a deletion that would be expected to shift the translational reading frame of the mRNA and give a severe phenotype. We have examined dystrophin and its mRNA from muscle biopsies of seven cases with either mild or intermediate phenotypes. In all cases we detected slightly lower-molecular-weight dystrophin in 12%-15% abudance relative to the normal. By sequencing amplified mRNA we have found that exon 2 is spliced to exon 8, a splice that produces a frameshifted mRNA, and have found no evidence for alternative splicing that might be involved in restoration of dystrophin mRNA reading frame in the patients with a mild phenotype. Other transcriptional and posttranscriptional mechanisms such as cryptic promoter, ribosomal frameshifting, and reinitiation are suggested that might play some role in restoring the reading frame. PMID- 1496989 TI - HLA heterozygosity contributes to susceptibility to rheumatoid arthritis. AB - We have investigated the role of HLA-DR genotypes in 184 patients with severe rheumatoid arthritis (RA) and in 46 patients with Felty syndrome, to establish the relative contribution of the RA-associated subtypes of DR4 (Dw4, Dw14, and Dw15). There was an excess of DR4 homozygotes, particularly Dw4/Dw14 compound heterozygotes (relative risk [RR] 49). The risk associated with Dw4 depended on the other allele present--Dw4/DR1 (RR 21), Dw4/Dw4 (RR 15), and Dw4/DRX (RR 6). There was a significant risk from Dw4/Dw14 compared with Dw4/Dw4, both in those with severe RA (RR 2.9; P less than .02) and in those with Felty syndrome (RR 4.2; P less than .02). In contrast, in a further 63 known DR4 homozygotes with RA, not selected for severe disease, the excess of Dw4/Dw14 was much less striking (RR 1.4; not significant), suggesting that this genotype may be particularly associated with more severe disease. We also found four cases with the rare Dw4/Dw15 genotype (expected less than or equal to 0.5; P less than or equal to .02). Since the Dw4, Dw14, Dw15, and DR1 molecules have similar antigen binding sites and since combinations of these alleles particularly predispose to severe RA, we suggest that synergistic mechanisms are involved. These could include an effect on T-cell repertoire selection. PMID- 1496990 TI - HLA-DR polymorphism in a Senegalese Mandenka population: DNA oligotyping and population genetics of DRB1 specificities. AB - HLA class II loci are useful markers in human population genetics, because they are extremely variable and because new molecular techniques allow large-scale analysis of DNA allele frequencies. Direct DNA typing by hybridization with sequence-specific oligonucleotide probes (HLA oligotyping) after enzymatic in vitro PCR amplification detects HLA allelic polymorphisms for all class II loci. A detailed HLA-DR oligotyping analysis of 191 individuals from a geographically, culturally, and genetically well-defined western African population, the Mandenkalu, reveals a high degree of polymorphism, with at least 24 alleles and a heterozygosity level of .884 for the DRB1 locus. The allele DRB1*1304, defined by DNA sequencing of the DRB1 first-domain exon, is the most frequent allele (27.1%). It accounts for an unusually high DR13 frequency, which is nevertheless within the neutral frequency range. The next most frequent specificities are DR11, DR3, and DR8. Among DRB3-encoded alleles, DR52b (DRB3*02) represents as much as 80.7% of all DR52 haplotypes. A survey of HLA-DR specificities in populations from different continents shows a significant positive correlation between genetic and geographic differentiation patterns. A homozygosity test for selective neutrality of DR specificities is not significant for the Mandenka population but is rejected for 20 of 24 populations. Observed high heterozygosity levels in tested populations are compatible with an overdominant model with a small selective advantage for heterozygotes. PMID- 1496991 TI - Microevolution of the Chibcha-speaking peoples of lower Central America: rare genes in an Amerindian complex. AB - Models are developed for the survival, history, and spread of variant alleles, in order to consider what can, and what cannot, be inferred from this type of data. The high variances of the processes involved, and questions of sampling, place severe limitations on inferences. Nonetheless, by combining information on a number of rare variants observed in a group of interrelated populations, reliable qualitative inferences are possible. These ideas and models are developed in the context of data on five rare variants and six private polymorphisms observed in eight Chibcha-speaking tribes of Costa Rica and Panama. The decline and fragmentation of the Amerindian populations of Central America over the last 300 years create considerable difficulties in attempting inference of past genetic events. However, these tribes have been well studied genetically, anthropologically, and linguistically and thus provide an excellent framework for the study of rare-variant spread. PMID- 1496992 TI - State legislative efforts to regulate use and potential misuse of genetic information. AB - The purpose of this study was to review existing and proposed legislation specifically intended to regulate the collection, use, and potential misuse of genetic data. The study encompasses laws relating to confidentiality, informed consent, discrimination, and related issues. It excludes from consideration legislation relating to medical records generally that may bear indirectly on genetic information. It also excludes both legislation relating to the regulation of DNA data collection for law enforcement purposes and state laws relating to the confidentiality of data collected by newborn-screening programs. While relatively few laws that explicitly regulate the treatment of genetic information have been enacted to date, a considerable amount of activity is currently underway in the nation's legislatures. Although most of the bills under consideration are not comprehensive in scope, they reflect a growing societal awareness that the uncontrolled dissemination and use of genetic data entails significant risks. PMID- 1496993 TI - Selection bias in genetic-epidemiological studies of cleft lip and palate. AB - The possible impact of selection bias in genetic and epidemiological studies of cleft lip and palate was studied, using three nationwide ascertainment sources and an autopsy study in a 10% sample of the Danish population. A total of 670 cases were identified. Two national record systems, when used together, were found suitable for ascertaining facial cleft in live births. More than 95% ascertainment was obtained by means of surgical files for cleft lip (with or without cleft palate) without associated malformations/syndromes. However, surgical files could be a poor source for studying isolated cleft palate (CP) (only a 60% and biased ascertainment), and they cannot be used to study the prevalence of associated malformations or syndromes in facial cleft cases. The male:female ratio was 0.88 in surgically treated cases of CP and was 1.5 in nonoperated CP cases, making the overall sex ratio for CP 1.1 (95% confidence limits 0.86-1.4) The sex ratio for CP without associated malformation was 1.1 (95% confidence limits 0.84-1.6). One of the major test criteria in CP multifactorial threshold models (higher CP liability among male CP relatives) must be reconsidered, if other investigations confirm that a CP sex-ratio reversal to male predominance occurs when high ascertainment is achieved. PMID- 1496994 TI - High frequency of mutations in exon 10 of the porphobilinogen deaminase gene in patients with a CRIM-positive subtype of acute intermittent porphyria. AB - Acute intermittent porphyria (AIP) is an autosomal dominant disease characterized by a partial deficiency of porphobilinogen (PBG) deaminase. Different subtypes of the disease have been defined, and more than 10 different mutations have been described. We focused our study on exon 10, since we previously found that three different mutations were located in this exon and that two of them seemed to be relatively common. We used denaturing gradient gel electrophoresis (DGGE) after in vitro amplification to detect all possible mutations in exon 10 in 41 unrelated AIP patients. In about one-fourth of these patients we could distinguish three abnormal migration patterns, indicating the presence of various mutations. Additional sequencing demonstrated the presence of three different single-base substitutions. Two of these mutations had already been described. A third one consisted of a C-to-T transition located at position 499 of the PBG deaminase mRNA and resulted in an Arg-to-Trp substitution. All three mutations were found in patients with cross-reacting immunological material (CRIM)-positive forms of AIP. The high frequency of these mutations make DGGE analysis of exon 10 a useful approach allowing the direct direction of the DNA abnormality in most of the families with the CRIM-positive subtype of AIP. PMID- 1496996 TI - Corrections to "Linkage strategies for genetically complex traits. III. The effect of marker polymorphism on analysis of affected relative pairs". PMID- 1496995 TI - Genetic studies to characterize the origin of the mutation in placental aromatase deficiency. AB - Placental aromatase deficiency has recently been shown to be due to expression of RNA transcripts encoding abnormal aromatase molecules with 29 extra amino acids. To establish whether this aromatase deficiency is a hereditary or sporadic disease, we examined the genetic defect of the aromatase gene in the family of a patient. Direct sequencing of fragments of the aromatase gene prepared by PCR revealed that the splicing donor sequence (GT) of intron 6 in controls was mutated to GC in the patient, whereas the parents showed signals of both GT and GC. Subcloning of PCR products of the parents gave two different types of clones with GT and GC sequences in this site. Furthermore, for diagnosis of this deficiency, competitive-oligo-nucleotide-priming PCR of genomic DNA was performed in the presence of both normal and mutational oligonucleotide primers labeled with two kinds of fluorescent dyes, and the products were separated by agarose gel electrophoresis and were detected fluorometrically in the gel. Genomic DNA of the patient gave a PCR product primed only by the mutational primer, whereas that of controls gave a product primed only by the normal primer. The PCR products of the parents were primed by both primers. The results obtained by this fluorometric method were also confirmed by differential hybridizations with specific oligonucleotide probes. Thus these findings indicate that this deficiency is an autosomal hereditary disease and that the patient is a homozygote, while the parents are heterozygotes, for this mutation. PMID- 1496997 TI - Screening Duchenne and Becker muscular dystrophy patients for deletions in 30 exons of the dystrophin gene by three-multiplex PCR. PMID- 1496998 TI - Smoking and cancer. AB - An extensive body of epidemiologic data has linked cigarette smoking to a wide variety of neoplastic diseases. Smokers have been found to incur an increased relative risk of mortality from cancer of the lung, head and neck, urinary tract, pancreas, and bladder. Recent work has also implicated smoking in the risk of leukemia and myeloma. The magnitude of these risks has prompted research aimed at identifying the carcinogens involved in specific smoking-related neoplasms, as well as potential genetic predispositions to the effects of these toxins. Mutations in tumor suppressor genes have been identified in both small-cell and non-small-cell lung cancer, and mutations in dominant oncogenes have been noted in the latter disease. A growing understanding of the molecular genetics of smoking-related cancers may translate into improved diagnosis and treatment. Detection of mutations in oncogenes or tumor suppressor genes in premalignant tissues might facilitate identification of individuals who have a hereditary predisposition to smoking-related carcinomas. In the future, tumor growth may be halted by replacement or substitution of mutated tumor suppressor gene functions or biochemical modulation of oncogene products. New forms of immunotherapy may also be targeted specifically toward mutant oncogenes in cancer cells. PMID- 1496999 TI - Mechanisms of respiratory tissue injury from cigarette smoking. AB - Cigarette smoking can be viewed as a chronic inflammatory disorder of the lower airways. Two of the major lung injuries that can result are chronic bronchitis and emphysema. Chronic bronchitis is characterized by chronic mucus hypersecretion and cough; emphysema is a destructive process of the alveolar spaces. Tissue injury may result from the actions of degradative enzymes derived from such inflammatory cells as neutrophils and monocytes. In addition, oxidative injury from inflammatory cells and from oxidants in smoke may participate in the pathogenesis of these smoking-related illnesses. PMID- 1497000 TI - The impact of tobacco use and cessation on oral and dental diseases and conditions. AB - Smoked and smokeless tobacco use produces profound effects on soft and hard tissues in and around the oral cavity. Because many of these changes are clinically observable, dentists, oral hygienists, and related health professionals are in ideal positions to give patients specific information concerning the oral ill effects of tobacco use. This article links tobacco use with a wide range of malignant, precancerous, and nonmalignant changes in the oral and perioral environment and addresses the documented benefits of quitting. Oral conditions less definitively linked to tobacco are also discussed. PMID- 1497001 TI - The effects of smoking on postoperative recovery. AB - Two recent studies have implicated smoking as a principal risk factor for increasing the time patients spend in the postanesthesia care unit (PACU) following a wide range of surgical procedures. Hospitals are performing an increasing number of surgical procedures, with growing pressure to do more on an outpatient basis. With more internal and external pressures to streamline the rising costs of medical care, increased focus is being placed on the length of stay in the PACU. More than 300 patients were examined in each study. PACU time varied from 15 minutes to 5 hours, with a median of 75 minutes. Anesthesia duration correlated most closely with the length of stay in the PACU. All other variables were found to be unrelated to the length of time in the PACU or secondary to anesthesia time. The only independent factor was a history of smoking. While there were comparable ratios of smokers in all tested groups, there was a marked difference between smokers and nonsmokers in length of PACU stay. Of the nonsmokers, 38% were found to have PACU stays of less than 1 hour, compared with 23% of the smokers. Only 7% of the nonsmokers required longer PACU stays, compared with 19% of the smokers. Among the various smoking groups, however, there were no significant differences. While previous studies have suggested that smokers may have higher rates of various perioperative complications, these two studies are significant in that they have identified a population previously overlooked. These people who stay longer in the PACU would not otherwise be identified as having complications, and their eventual outcome was good. But it suggests that even these patients, who may view themselves as "healthy smokers," are significantly different from their nonsmoking counterparts. Further, varying the degree of smoking from heavy to light does not negate the increased PACU time. Therefore, any degree of smoking must now be viewed as having serious consequences in the immediate postoperative period and must be discouraged. PMID- 1497002 TI - Passive smoking: the medical and economic issues. AB - Since the late 1970s, the dangers associated with passive (involuntary) smoking have been widely debated. While research throughout the world has produced findings showing sidestream smoke to be harmful and possibly deadly to nonsmokers, an equal number of studies have indicated that the harms have been overstated or misclassified or that they are nonexistent. Those debates have culminated in a report sponsored by the Environmental Protection Agency and other federal agencies. The report concludes that second-hand cigarette smoke kills 53,000 nonsmokers a year and is a major cause of indoor air pollution. This article identifies the major medical and economic issues in the debate on side stream smoke. It affirms the federal government's position on the need to create more smoke-free environments and impose stronger smoking restrictions nationwide. PMID- 1497003 TI - Impact and cost-effectiveness of smoking interventions. AB - Cigarette smoking is the foremost preventable cause of death in the United States. Along with being a major contributor to lung cancer, chronic obstructive pulmonary disease, and cerebrovascular disease, smoking is one of several modifiable risk factors for coronary artery disease (CAD). The Coronary Heart Disease Policy Model is a computer simulation model of CAD in the United States. Using the model, one can project CAD incidence, prevalence, events, mortality, cost, cost-effectiveness, and gains in life expectancy from various risk factor modifications, including smoking interventions. The model projects that reducing the number of cigarettes smoked by 50% would increase the population-wide life expectancy of 35-year-old U.S. citizens by 0.4 year. Eliminating smoking would yield population-wide gains of 0.8 year for 35-year-old males and 0.7 year for 35 year-old females. These gains are comparable to those achieved with strict control of cholesterol levels, diastolic blood pressure, or weight. Gains for the smokers themselves would be much greater. On average, 35-year-old male smokers would live 1.2 years longer if they reduced the number of cigarettes smoked by 50%, and 2.3 years longer if they quit smoking. Females 35 years of age would live 1.5 years longer by cutting back by 50% and 2.8 years longer by quitting. These gains are equal to or greater than gains that individuals would realize by reducing serum cholesterol levels of 240-299 mg/dL to 200 mg/dL; controlling mild hypertension; or reducing weight from greater than or equal to 130% ideal body weight to ideal body weight. Gains projected by the Coronary Heart Disease Policy Model are comparable to those forecast by others, who have projected that young adults would gain approximately 0.2-8.7 years by quitting smoking, depending on their smoking history. Two studies have examined the cost-effectiveness of smoking interventions. One found that counseling smokers to quit would cost only $705-988 per year of life saved for males and $1,204-2,058 per year of life saved for females. The second study found that prescribing nicotine gum as an adjunct to counseling would cost only $4,113-6,465 per year of life saved for males and $6,880-9,473 per year of life saved for females. These cost-effectiveness ratios are more favorable than those of most other current healthcare interventions. Smoking cessation would increase population-wide life expectancy by about a year and the life expectancy of a smoker by several years.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1497004 TI - Corporate healthcare costs and smoke-free environments. AB - Results from two studies were combined to assess potential market impact for programs to reduce health risks, as well as to define how small businesses can better control their healthcare operating expenses, widen their profit margins, and increase their productivity. The most effective solutions resulted from partnerships among the medical, business, and patient communities for the joint implementation of intensive smoking-cessation programs. In the first study, the chief executive officers of 1,100 small businesses in the Chicago area were polled regarding their opinions on healthcare costs. During the 4-year study period, 1986-1990, we observed a significant increase in their recognition of the impact of employee smoking on rising healthcare costs. From this study we identified three profile attributes of small-business leaders. First, these leaders possess a weak knowledge base regarding healthcare cost-containment methods; second, they understand the magnitude of the impact-rising healthcare costs have on corporate profitability; and third, they have a strong level of confidence (85%) that lifestyle modification programs for their employees, such as smoking cessation, can help control healthcare costs. In the second study we found that smoking-cessation programs with physician involvement, addiction assessment and treatment, and behavioral training and follow-up are preferred by those who want to stop smoking. Such programs have also enjoyed the highest level of sustained success. PMID- 1497005 TI - Smoking and cardiovascular disease. AB - Cigarette smoking is the most preventable cause of cardiovascular morbidity and mortality. Smoking has been associated with a two-to fourfold increased risk of coronary heart disease, a greater than 70% excess rate of death from coronary heart disease, and an elevated risk of sudden death. These risks are compounded in the presence of hypertension, hypercholesterolemia, glucose intolerance, and diabetes, all of which exhibit a synergistic effect with smoking. The relationship between smoking and the risk of peripheral vascular disease has also been well documented. Smokers account for approximately 70% of patients with atherosclerosis obliterans and virtually all those with thromboangiitis obliterans. An association between smoking and cerebrovascular disease remains a matter of debate, although a higher risk of stoke and stroke-related mortality has been observed in smokers than in nonsmokers. Smoking has also been implicated in the development of cor pulmonale, but a direct association with congestive heart failure has not been established. Nicotine and carbon monoxide appear to play major roles in the cardiovascular effects of smoking. Both components adversely alter the myocardial oxygen supply/demand ratio and have been shown to produce endothelial injury, leading to the development of atherosclerotic plaque. Adverse effects on the lipid profile have been noted as well, but the relationship between these changes and the risk of cardiovascular disease remains to be confirmed. Notably, smoking cessation results in a dramatic reduction in the risk of mortality from both coronary heart disease and stroke. In light of the fact that the incidence of smoking has declined primarily among educated sectors of the U.S. population, future efforts must focus on providing effective education, including smoking cessation techniques, to the less-educated groups. PMID- 1497006 TI - Rapid infusion of amphotericin B: is it safe, effective, and wise? PMID- 1497007 TI - Rapid intravenous infusion of amphotericin B: a pilot study. AB - PURPOSE: The administration of amphotericin B in the conventional prolonged infusion over 4 to 6 hours is complicated by the acute toxicities of fevers and chills in 50% to 90% of patients and the chronic toxicities of increased creatinine levels and hypokalemia in 60% to 80% of patients. To determine the safety and toxicity of rapid infusions, we conducted a prospective, nonrandomized study in patients with clinical indications for antifungal therapy. PATIENTS AND METHODS: Twenty-five granulocytopenic adults with acute leukemia and myelodysplastic syndromes were enrolled in a phase I trial using four sequentially shorter infusion durations: a standard infusion over 4 hours (n = 3) and shortened infusion durations at 3 hours (n = 3), 2 hours (n = 4), and 1 hour (n = 15). Toxicity was assessed by daily examinations of study subjects by one of the study investigators, by documentation of all infusion-related fevers and chills, and by daily monitoring of serum levels of creatinine, potassium, magnesium, and aspartate aminotransferase. RESULTS: Temperatures greater than 38 degrees C occurred in 16 of 25 (64%) patients, but only two had temperatures exceeding 40 degrees C. Chills were observed in 13 of 25 (56%) patients, but only one had severe symptoms. Serum creatinine increased more than 0.5 mg/dL (44.20 mumol/L) above the pretreatment baseline in 17 of 25 (68%) patients, and the absolute creatinine level was greater than or equal to 2.0 mg/dL (176.8 mumol/L) in 10 of 25 (40%) patients. Serum potassium levels dropped below the normal limit of 3.5 mEq/L (3.5 mmol/L) in all patients, but no patient had potassium levels below 2.5 mEq/L (2.5 mmol/L). Intravenous potassium supplementation was administered to all patients and exceeded 100 mEq/d in 12 of 25 (48%) patients. CONCLUSIONS: Rapid infusions of amphotericin B are safe, are associated with similar toxicity as prolonged infusions, and facilitate inpatient care by decreasing nursing time needed for administration and minimizing scheduling conflicts with other necessary intravenous medications. Shorter infusions also facilitate outpatient and home administration of amphotericin B. PMID- 1497008 TI - A pilot study of oral corticosteroid therapy for idiopathic esophageal ulcerations associated with human immunodeficiency virus infection. AB - PURPOSE: To evaluate the efficacy and safety of oral prednisone therapy for idiopathic esophageal ulcerations (IEU) associated with human immunodeficiency virus (HIV) infection. PATIENTS AND METHODS: Over a 14-month period, all HIV infected patients with IEU as defined by clinical, endoscopic, and pathologic criteria were prospectively identified. Prednisone was initiated at a dose of 40 mg/d orally, tapering 10 mg/wk, for a total of 1 month of therapy. Patients were closely followed to determine the response to therapy as well as the occurrence of any side effects related to prednisone. All patients were requested to undergo endoscopy within 1 week of the completion of therapy. RESULTS: Of 14 patients identified with IEU, 12 consented to prednisone therapy. The mean duration of esophageal symptoms was 2.9 weeks, and odynophagia was the most common presenting symptom. Ten of 12 patients had the acquired immunodeficiency syndrome. Eleven of the 12 patients (92%) had a complete symptomatic response, usually within the first week of therapy. In some patients, the response was dramatic such that oral intake could be rapidly resumed and discharge from the hospital possible. Two patients completed 2 and 3 weeks of therapy, respectively, prior to death, both with a complete symptomatic response. Endoscopic re-examination in seven patients demonstrated complete ulcer healing in all six symptomatic responders, but a persistent ulceration in the one nonresponder. The oral corticosteroid regimen was well tolerated. Mild asymptomatic Candida esophagitis was identified in three of seven patients undergoing follow-up endoscopy. One patient developed self limited herpes zoster during therapy. No systemic opportunistic infections were documented during or within 1 month of the completion of therapy. CONCLUSIONS: Oral corticosteroid therapy appears to be a highly efficacious and safe therapy for HIV-associated IEU. Further controlled studies will be necessary to conclusively establish efficacy, as well as determine the optimal dose and duration of therapy. PMID- 1497009 TI - A predictive risk index for nosocomial pneumonia in the intensive care unit. AB - PURPOSE: To develop a scoring system for stratifying patients in intensive care units (ICUs) by risk of developing nosocomial pneumonia (NP) and to identify the time period associated with the highest risk. PATIENTS AND METHODS: Two hundred and three patients 18 years of age or older and residing in the ICU for 72 hours or more were followed until development of NP or death or for 48 hours after discharge from the ICU. After the identification of independent risk factors for NP, a scoring system was developed to arrive at a predictive risk index for NP. RESULTS: Twenty-six (12.8%) patients developed NP. The presence of a nasogastric (NG) tube [odds ratio (OR) = 6.48, 95% confidence intervals (CI) = 2.11 to 19.82], upper abdominal/thoracic surgery (OR = 4.34, 95% CI = 1.43 to 13.14), and bronchoscopy (OR = 2.95, 95% CI = 1.02 to 8.52), most commonly performed for respiratory toilet, were identified as independent risk factors on multivariate analysis. The risks associated with endotracheal intubation and altered consciousness, although not independently significant, were highest when these factors were present for 1 to 4 days after the 72 hours required for study entry (endotracheal intubation, OR = 2.2 to 2.5; altered consciousness, OR = 1.4 to 2.0). The risk then declined; ORs of less than 1 were observed at 7 days. The risk associated with the NG tube was highest during the first 6 days (OR = 6.0 to 19.5). Although a subsequent decrease in risk was observed, the OR was still greater than 2 at 7 days. To obtain a predictive risk index for NP, a scoring system was developed using a multivariate model. This system has a sensitivity of 85% and a specificity of 66% in predicting NP in this ICU population. CONCLUSION: ICU patients can be stratified into high- and low-risk groups for NP using a bedside scoring system. Endotracheal intubation, altered mental status, and NG tube are associated with the highest risk of NP during the first 1 to 6 days of their presence after 72 hours of stay in the ICU. After this time period, the risk associated with these factors decreases. Bronchoscopy may be an independent risk factor for NP that has not been previously recognized. This procedure, often done in the ICU for respiratory toilet, may be an avoidable risk in this group of patients. PMID- 1497010 TI - Autonomic dysfunction in systemic sclerosis: sympathetic overactivity and instability. AB - PURPOSE: This study was designed to assess the prevalence and nature of autonomic dysfunction (AD) in 34 patients with systemic sclerosis (SSc). PATIENTS AND METHODS: Patients were questioned for current symptoms possibly related to AD. Five noninvasive cardiovascular autonomic function tests and sequential plasma catecholamine estimations at rest, during standing, and during sustained handgrip were performed. Seven patients with manometrically documented esophageal involvement and high resting plasma adrenaline levels were treated with clonidine (75 to 375 micrograms/d). One month later, resting plasma catecholamine estimations and esophageal motility studies were repeated. RESULTS: Autonomic testing revealed AD in each patient, while symptoms were experienced by 33 of them. Findings on two of the three heart rate tests and both blood pressure tests were significantly impaired as compared with those in 25 matched control subjects. Mean resting plasma adrenaline levels were 18 times higher than in 10 matched controls (p less than 0.001). Plasma catecholamine (adrenaline, noradrenaline, and dopamine) concentrations and mean arterial blood pressures fluctuated inappropriately during standing and sustained handgrip in 28 (82%) of the patients. The presence of headaches correlated significantly with sympathetic overactivity and instability (p less than 0.05). Resting plasma adrenaline concentrations correlated inversely with disease duration (p less than 0.05). Significant suppression of sympathetic overactivity and increases in resting lower esophageal sphincter pressures were observed in the seven patients treated with clonidine. CONCLUSION: AD is extremely common in SSc. It is characterized by parasympathetic impairment and marked sympathetic overactivity, particularly in early disease. The potential role of AD in the pathogenesis of SSc deserves further study. PMID- 1497011 TI - Effect of two French nurses' strikes on mortality in a geriatric hospital. AB - PURPOSE: To study the influence of the 1988 French nurses' strikes on mortality in a geriatric hospital. MATERIALS AND METHODS: Two nurses' strikes affected the Charles Foix Hospital near Paris from June 29 to July 31 and from September 17 to October 22, 1988. Mortality was studied in nine geriatric wards of this hospital, including two rehabilitation units comprising 187 beds, and seven long-term care units comprising 1,132 beds. Monthly mortality rates were calculated from the hospital's administrative registers and expressed as deaths per 1,000 patient days. These rates were calculated in each of the aforementioned nine units for the 36 months preceding the first strike (control period) and for the 12 months following it (study period). RESULTS: Over the control period, monthly mortality was significantly higher in rehabilitation units than in long-term care units (2.46 +/- 1.21 versus 0.83 +/- 0.47, p less than 0.001), but mortality rates among rehabilitation units, as well as among long-term care units, were comparable. Also, during the control period, large seasonal fluctuations in monthly mortality rates were observed in both rehabilitation units and long-term care units (peak in winter and nadir in summer). These rates tended to decrease from year to year in rehabilitation units but not in long-term care units. A statistical model based on time-series analysis of the control period data was used to calculate the expected monthly mortality rates for the study period in rehabilitation units and in long-term care units, respectively. Three of the 12 actual monthly mortality rates exceeded the upper limit of the 95% confidence interval of the 12 expected monthly mortality rates, in the units where the more severe care disruption occurred. A detailed analysis of discharge summaries of these units failed to identify a possible link between some of these deaths and a possible absence of care. CONCLUSIONS: The nurses' strikes did not induce a clear cut increase in mortality in this population of elderly patients. However, we cannot exclude the possibility that these strikes had some negative effects on health. Our results fail to provide answers to the difficult ethical problems created by such stoppages. PMID- 1497012 TI - Sinusitis in HIV-infected patients: a clinical and radiographic review. AB - PURPOSE: To describe the clinical, radiographic, and laboratory features of sinus disease in human immunodeficiency virus (HIV)-infected individuals. PATIENTS: Seventy-two patients with a history of sinusitis identified from 1,461 consecutive admissions (667 patients) to the HIV ward at The Johns Hopkins Hospital. METHODS: Retrospective chart review. SETTING: The Johns Hopkins Hospital. RESULTS: Sinusitis was identified in 72 HIV-infected patients, predominantly individuals with a CD4 cell count of less than 200/mm3. A history of respiratory infections such as bacterial pneumonia, bronchitis, and otitis media was common. Although nasal congestion and postnasal drainage were found in the majority of patients, symptoms of sinusitis were often nonspecific and the diagnosis was incidental in 28 patients (33%). Magnetic resonance imaging or computed tomography was significantly more sensitive than plain radiography (p less than 0.001) in defining the extent of the disease, particularly with posterior sinus involvement, which occurred in the majority of the patients. The number of radiologically abnormal sinuses correlated inversely with the CD4 count. Although the majority of patients responded at least partially to antibiotic therapy, only 15% had complete resolution of clinical symptoms. Fifty eight percent of patients had clinical and/or radiographic evidence of recurrent/persistent sinus infection, and chronicity correlated with a CD4 count less than 200/mm3 (p less than 0.001). CONCLUSIONS: Sinusitis in HIV-infected patients is common, severe, and difficult to treat. Patients with CD4 counts less than 200/mm3 are prone to disease involving multiple sinuses that responds incompletely to antibiotic therapy, often resulting in chronic sinusitis. Unlike the immunocompetent host, the majority of the HIV-infected patients with advanced immunodeficiency develop posterior sinus disease. PMID- 1497013 TI - Long-term complications of arteriohepatic dysplasia. AB - PURPOSE: It has been stated that arteriohepatic dysplasia is a form of biliary paucity with a good prognosis. We wished to determine the long-term morbidity and mortality associated with arteriohepatic dysplasia. PATIENTS AND METHODS: The charts of all patients with arteriohepatic dysplasia followed by the pediatric gastroenterologists of the University of Minnesota into adulthood were reviewed. RESULTS: Over the last 33 years, the pediatric gastroenterologists have followed 16 children with syndromic paucity, six of whom are now beyond age 18 years. Although five of six patients responded to medical therapy with improvement in their cholestasis and appeared stable clinically through childhood, five of six patients had complications of arteriohepatic dysplasia after age 16 years that resulted in severe morbidity (three) or death (two). These complications included hepatic failure (two), renal failure (one), cerebellar herniation (one), and hepatocellular carcinoma (one). In only one patient were symptoms of the complications present prior to the age of 18 years. CONCLUSION: As more patients with arteriohepatic dysplasia reach adulthood, it appears that this syndrome may be accompanied by long-term manifestations extending beyond childhood. It is important that physicians assuming management of these patients from pediatricians be aware that new abnormalities may appear without warning and that the hepatic disease may deteriorate despite apparent stability through childhood. PMID- 1497014 TI - Reactive hemophagocytic syndrome--a clinicopathologic study of 40 patients in an Oriental population. AB - PURPOSE: The purpose of this investigation was to assess the clinical spectrum and outcome of reactive hemophagocytic syndrome (RHS) in an Oriental population. PATIENTS AND METHODS: The investigation was a retrospective study of 40 consecutive patients with RHS diagnosed over a 4-year period in Queen Elizabeth Hospital, a community-based hospital in Hong Kong. RESULTS: The incidence of RHS in Hong Kong appeared to be comparable with that of Western countries. However, the spectrum of diseases associated with RHS was distinctly different. Forty percent of the cases were associated with malignant lymphoma. Another 40% of the cases were associated with infection, often due to bacteria, and infection due to the herpes group of viruses was uncommon, probably reflecting ethnic and geographic differences from the white population. Two patients had the acute lupus hemophagocytic syndrome, a distinctive form of RHS that occurs in patients with systemic lupus erythematosus. Treatment was basically supportive, with specific therapy also given for the underlying disease if present. Eighteen patients (45%) died of the acute disease, mostly as a result of complications of RHS or the underlying diseases. The development of disseminated intravascular coagulopathy was a poor prognostic factor. CONCLUSIONS: RHS is an uncommon disorder in Hong Kong and is often associated with malignant lymphoma or bacterial infection. A rigorous search for an underlying malignancy or infection is thus warranted once this diagnosis is made. PMID- 1497015 TI - Association of anti-beta 2 glycoprotein I antibodies with lupus-type circulating anticoagulant and thrombosis in systemic lupus erythematosus. AB - PURPOSE: Antiphospholipid antibodies (including anticardiolipin antibodies and circulating anticoagulant) are associated with thrombosis in systemic lupus erythematosus. Since it has been shown that beta 2 glycoprotein I (beta 2 gp I) acts as a cofactor of anticardiolipin antibody binding to cardiolipin, the presence and clinical meaning of anti-beta 2gp I antibodies in sera from patients with lupus were examined. PATIENTS AND METHODS: An enzyme-linked immunosorbent assay technique for the detection of anti-beta 2gp I antibodies was developed, and 47 lupus sera were studied retrospectively, as well as 88 healthy blood donors' sera. RESULTS: It was found that 17 of 47 patients with lupus (36%) had anti-beta 2gp I antibodies. Anti-beta 2gp I antibodies were statistically associated with anticardiolipin antibodies, thrombosis, and lupus anticoagulant. Eight of nine lupus patients with thrombosis had anti-beta 2gp I antibodies and lupus anticoagulant, and seven of them had anticardiolipin antibodies. Of 18 patients with anticardiolipin antibodies without anti-beta 2gp I antibodies or lupus anticoagulant, only one had thrombosis (due to nephrotic syndrome). Among anti-beta 2gp I-positive patients, 14 of 16 had lupus anticoagulant activity, whereas only three patients with lupus anticoagulant were anti-beta 2gp I negative. CONCLUSIONS: The presence of anti-beta 2gp I antibodies is a new immunologic feature of lupus patients with thrombosis. In addition, since anti beta 2gp I antibodies are closely associated with lupus anticoagulant activity, they may contribute to explain antiprothrombinase activity. PMID- 1497016 TI - A clinical overview of dyslipidemias: treatment strategies. AB - The strong epidemiologic relationship between specific lipoprotein levels (such as elevated low-density lipoprotein cholesterol or decreased high-density lipoprotein cholesterol) and the future development of coronary heart disease has been well documented. Within the past several years, landmark clinical trials have clearly demonstrated that the incidence of coronary heart disease events is reduced when lipoprotein abnormalities are corrected via pharmacologic therapy. These findings have prompted clinicians to become more vigilant with regard to recognition of dyslipidemias and institution of treatment. This review focuses on the more common primary and secondary dyslipidemias and the currently available lipid-lowering therapies for each disorder. Results of recent coronary angiographic trials are discussed, and implications for the medical management of established coronary heart disease are assessed. PMID- 1497017 TI - New therapeutic agents in the treatment of inflammatory bowel disease. AB - Despite intense investigation, the etiology of inflammatory bowel disease (IBD) remains unknown. Recent studies with new therapeutic agents provide insight into the pathogenesis of IBD through analysis of the clinical response to pharmacologic agents whose mechanism of action is understood. Until new agents are established, IBD will be treated with conventional drugs directed toward modifying the inflammatory responses responsible for gastrointestinal mucosal damage. Sulfasalazine, mesalamine (5-aminosalicylic acid), and corticosteroids will continue to be the mainstay of therapy for the foreseeable future. Antibiotics such as metronidazole and immunosuppressants such as 6-mercaptopurine and methotrexate are useful in Crohn's disease and ulcerative colitis in selected cases. Many new exciting agents are being investigated and show encouraging results in the treatment of IBD. This article reviews the agents used in IBD with an emphasis on new therapeutic agents. PMID- 1497018 TI - The stigma of disease: implications of genetic screening. AB - As the field of human genetics successfully continues to unravel the secrets of an individual's genetic makeup, the social processes of stigmatization and ostracism of those with "undesirable" traits have the potential to increase. An historical example that may shed light on the problems of applying genetic technology to disease prevention is the institution of quarantine. This essay discusses the concept of "quarantine mentality" and the desire for healthy society to separate itself from those labeled "ill" or abnormal, and addresses two episodes in American history when genetics was applied to the formulation of social policy toward the "diseased": the eugenics movement of the early 20th century and the early attempts of genetic screening programs for sickle cell anemia during the 1970s. PMID- 1497019 TI - Expanding the boundaries of informed consent: disclosing alcoholism and HIV status to patients. AB - Since informed consent became legally required in the therapeutic setting, the risks physicians were to disclose have been limited to the risks of particular procedures. Two recent court decisions in which disclosure of surgeons' alcoholism and positive human immunodeficiency virus status was required may begin to erode that limit. The grounds for this expansion of disclosure requirements were inherent in the 20-year-old "materiality" standard for disclosure; nevertheless, the change they signal is profound. These cases may signal a trend that, in the long term, could result in a shift in physician patient communication and a significant loss of privacy for physicians. PMID- 1497020 TI - Hepatic angiosarcoma. AB - A patient with hepatic angiosarcoma is described. The significant aspects of this malignancy are delineated. This tumor constitutes only 2% of all primary tumors of the liver. The association with exposure to vinyl chloride and other carcinogens is reviewed. Diagnostic and therapeutic modalities are discussed. PMID- 1497021 TI - Chronic hyponatremia due to resetting of the osmostat in a patient with gastric carcinoma. AB - A 54-year-old schizophrenic patient who presented with hyponatremia and nephrotic range proteinuria was subsequently discovered to have a gastric adenocarcinoma. Psychogenic water drinking, sodium depletion, and cardiac, adrenal, hepatic, and thyroid disease were excluded as causes of hyponatremia. The serum creatinine concentration was normal, and, although renal biopsy showed changes consistent with immune complex glomerulopathy, proteinuria remitted without treatment. Moderately severe hyponatremia persisted, and the diagnosis of gastric adenocarcinoma was made after the onset of early satiety 1 year later. Surgical exploration at the time of partial gastric resection revealed local metastatic lymph node involvement. Following the patient's uneventful recovery from surgery, studies of osmoregulation of vasopressin release and renal water handling were performed to determine the cause of chronic hyponatremia refractory to sodium chloride administration. Oral water loading studies revealed normal urinary diluting ability and appropriate suppression of plasma vasopressin concentrations. However, hypertonic sodium chloride infusion studies revealed a highly significant correlation between plasma osmolality and plasma vasopressin concentration, and a low osmotic threshold for vasopressin release based on linear regression analysis of the plasma vasopressin response to increasing plasma osmolality. Low osmotic threshold for vasopressin release was confirmed by exponential (log linear) and parabolic methods of data analysis. The findings in these studies are consistent with the typical features of the reset osmostat variant of the syndrome of inappropriate antidiuresis. To our knowledge, this is the first report of the occurrence of this syndrome in association with gastric adenocarcinoma. PMID- 1497022 TI - Diagnosis of giant cell arteritis by occipital artery biopsy. PMID- 1497023 TI - Selective loss of optic nerve beta-tubulin in vincristine-induced blindness. PMID- 1497024 TI - Interleukin-2 treatment, interferon-gamma induction, and AIDS monocyte activation. PMID- 1497025 TI - Erythropoietin in an anephric patient with adrenal medullary hyperplasia. PMID- 1497026 TI - Ambiguities of current issues in hypercholesterolemia. PMID- 1497027 TI - Experimental models of stroke. PMID- 1497028 TI - Malabsorption due to gastrointestinal histoplasmosis. PMID- 1497029 TI - Teenage pregnancy prevention: the vital importance of the medical community's involvement. PMID- 1497030 TI - Attenuated proestrous luteinizing hormone surges in middle-aged rats are associated with decreased pituitary luteinizing hormone-beta messenger ribonucleic acid expression. AB - OBJECTIVE: This study determined whether attenuated preovulatory luteinizing hormone surges in aging rats are associated with a decrease in pituitary luteinizing hormone content or luteinizing hormone beta-messenger ribonucleic acid expression on proestrus. STUDY DESIGN: Blood samples were taken every 90 minutes from 1:30 to 10:30 PM on proestrus in young (n = 8) and middle-aged (n = 12), regularly cyclic rats for plasma luteinizing hormone determination. On the next proestrus at 12 noon, rats were killed and the pituitaries were removed for luteinizing hormone content determination by radioimmunoassay and luteinizing hormone beta-messenger ribonucleic acid expression by dot blot analysis. Results were analyzed by one-way analysis of variance. RESULTS: Seven of the middle-aged rats had attenuated luteinizing hormone surges while the remaining five females had surges similar to those of young rats. On the next proestrus, all rats had similar quantities of pituitary luteinizing hormone. However, luteinizing hormone beta-messenger ribonucleic acid expression in middle-aged rats with attenuated luteinizing hormone surges was lower (p less than 0.05) than that of middle-aged and young rats with normal surges. CONCLUSION: Decreased luteinizing hormone beta messenger ribonucleic acid expression, but not pituitary luteinizing hormone content at 12 noon on proestrus is correlated with attenuated luteinizing hormone surges in middle-aged rats. PMID- 1497031 TI - Etiologic factors of recurrent abortion and subsequent reproductive performance of couples: have we made any progress in the past 10 years? AB - OBJECTIVES: We hypothesize that the diagnostic yield and pregnancy outcomes of patients with recurrent abortion have improved over the past 10 years. STUDY DESIGN: The study was performed in an academic medical center. Diagnoses and outcomes for group A, a published series of 100 patients investigated for recurrent abortion in the section between 1968 and 1977, was compared with those for group B, the 131 patients seen between 1987 and 1991. A standardized protocol was followed, enhanced by new techniques and autoimmune investigations in the latter group. Results were compiled retrospectively. Descriptive statistics and chi 2 analysis were used. RESULTS: No cause could be found in 37% of patients in group A compared with 24% of couples in group B (p less than 0.05). No clear difference could be shown in the subsequent outcomes of pregnancies. CONCLUSIONS: Our ability to establish a cause of recurrent abortion has improved slightly over the past 15 years. The gain is not yet reflected in successful pregnancy rates. Multicenter trials are indicated. PMID- 1497032 TI - Electroejaculation in combination with in vitro fertilization and gamete micromanipulation for treatment of anejaculatory male infertility. AB - OBJECTIVE: Failure to ejaculate may be overcome by use of electroejaculation. However, such semen samples are often unsuitable for therapies like intrauterine insemination. The combination of electroejaculation with in vitro fertilization, including gamete micromanipulation, should improve chances of fertilization and pregnancy in such cases. STUDY DESIGN: Within a private infertility clinic electroejaculation in combination with intrauterine insemination was carried out in 18 cycles (10 couples). Four couples went on to receive therapy by electroejaculation plus in vitro fertilization, along with six other couples (15 cycles total) with semen too poor for intrauterine insemination. RESULTS: One term pregnancy arose in the electroejaculation-intrauterine insemination group, and one term pregnancy plus one continuing pregnancy arose from two couples (three cycles) who underwent in vitro fertilization with conventional insemination after electroejaculation. Six couples (nine cycles) had embryos arising only from gamete micromanipulation transferred, and this yielded two term pregnancies, one spontaneous abortion, and a biochemical pregnancy. Two couples (three cycles) failed to achieve fertilization even with micromanipulation; however, donor-inseminated eggs gave rise to two term pregnancies and one continuing pregnancy in these patients. CONCLUSIONS: This report confirms the feasibility of in vitro fertilization in conjunction with electroejaculation and extends the therapy to incorporate gamete micromanipulation. PMID- 1497033 TI - Red blood cell transfusion and cesarean section. AB - OBJECTIVE: Our objective was to determine the incidence of blood transfusion in patients delivered by cesarean section and to identify factors predictive of the need for transfusion. STUDY DESIGN: A chart review was performed on cesarean patients receiving blood transfusion over a year at the Medical College of Virginia Hospital and an equal number of randomly selected cesarean patients. RESULTS: Sixty-one (6.8%) patients received a packed red blood cell transfusion intraoperatively or postoperatively. Transfusion was associated with lower gestational ages, antepartum bleeding, arrest of descent, and longer postoperative stays. After stepwise logistic regression analysis, only antepartum bleeding and preoperative hemoglobin were significant independent predictors of the need for blood transfusion. CONCLUSION: Transfusion with cesarean section is common and is associated with antepartum bleeding and other primarily intrapartum and unpredictable factors. PMID- 1497034 TI - Amnioinfusion: an aid in the ultrasonographic evaluation of severe oligohydramnios in pregnancy. AB - OBJECTIVE: Amnioinfusion was used in pregnancy complicated by severe oligohydramnios to enable a more comprehensive ultrasonographic evaluation of the pregnancy. STUDY DESIGN: Thirteen patients were referred to the Division of Obstetrical and Gynecological Ultrasound at the University of Miami because of severe oligohydramnios in which a definitive diagnosis could not be made. Nine patients were in the second trimester and four were in the early third trimester. All patients underwent amnioinfusion with warm physiologic saline solution and instillation of indigo carmine. Genetic amniocentesis was performed in 11 patients. RESULTS: After amnioinfusion a satisfactory comprehensive ultrasonographic examination could be performed on all patients. In most cases we were able to achieve a definitive diagnosis. CONCLUSION: Amnioinfusion with the addition of indigo carmine was a satisfactory technique to enable a more comprehensive ultrasonographic evaluation of pregnancy complicated by severe oligohydramnios. PMID- 1497035 TI - Long-term outcome in fetal hydrops from parvovirus B19 infection. AB - Parvovirus B19 infection in the fetus is associated with anemia and hydrops and can result in fetal death. Fetal transfusion has been used in an attempt to improve outcome; however, it is associated with its own perinatal morbidity. We report two cases of fetal parvovirus B19 infection that were confirmed by polymerase chain reaction for parvovirus B19 deoxyribonucleic acid in umbilical cord blood. Ultrasonographic signs of compromise were observed at 30 and 24 weeks of gestation. Both fetuses were hydropic and one fetus was also anemic. Serial sonograms demonstrated that the hydrops resolved spontaneously over 3 to 5 weeks after diagnosis. One infant was delivered at 32 weeks of gestation as a result of idiopathic preterm labor. The other infant was delivered at term. Both infants appeared relatively normal at birth and have developed normally in the first year of life. Thus fetal hydrops in association with parvovirus B19 infection does not always lead to poor long-term outcome. A conservative approach without in utero therapy may be appropriate for the management of some of these fetuses. PMID- 1497036 TI - Experience with mepivacaine paracervical block in an obstetric private practice. AB - OBJECTIVE: The objective of this study was to determine the efficacy and safety of mepivacaine paracervical block in term, low-risk obstetric patients. STUDY DESIGN: Over a 3-year period all term, low-risk obstetric patients in the author's private practice were offered mepivacaine paracervical block anesthesia. One hundred eighty-two patients received 200 mg mepivacaine with each block. The patients who declined paracervical block were used as a control group to compare Apgar scores, subject to chi 2 analysis. RESULTS: Initial injections were 97.3% successful. Average duration of anesthesia was 59.7 minutes with the first injection. Fetal bradycardia occurred in 13.2% with an average duration of 4.5 minutes. The slightly higher incidence of low Apgar scores at 1 and 5 minutes in the study group was not statistically significant. One neonatal death occurred secondary to group B streptococcal sepsis in the study group. CONCLUSION: Mepivacaine paracervical block remains an anesthetic option in low-risk patients. The high success rate is limited by its short duration of action and the incidence of fetal bradycardia. PMID- 1497037 TI - Refining the biophysical profile with a risk-related evaluation of test performance. AB - OBJECTIVE: Our objective was to determine the ability of biophysical profile variables to predict bad perinatal outcome in high-risk third-trimester pregnancy. STUDY DESIGN: The outcomes of 1146 fetuses were correlated with abnormal single or multiple variables occurring in biophysical profile done within 72 hours of delivery. Theoretic risks of poor outcomes for different combinations of abnormal variables, calculated with Shortlife's formula, were compared with the actual risks observed (chi 2 tests). RESULTS: Two hundred forty six fetuses had at least one abnormal biophysical profile variable with the risk of bad outcome, for a single abnormal variable, ranging from 8% (body movements) to 100% (tone) and increasing from 14% (any variable abnormal) to 63% (all variables abnormal). In most (57%) observed combinations of biophysical profile variables, significant differences between theoretic and actual risks of bad outcomes were found. By stepwise logistic regression the best predictive model contained all variables except fetal movement. CONCLUSIONS: Dynamic biophysical profile variables appear to be interdependent. Not all combinations of abnormal variables occur and specific combinations improve prediction of poor outcome. Risk-related scales for biophysical profile outcomes might prove superior to more conventional scoring systems. PMID- 1497038 TI - Excessive maternal weight and pregnancy outcome. AB - OBJECTIVES: This study was undertaken to determine the influences of increased maternal prepregnancy weight and increased gestational weight gain on pregnancy outcome. STUDY DESIGN: This was a longitudinal retrospective study of 7407 term pregnancies delivered from 1987 through 1989. After excluding cases with multiple fetuses, stillbirths, fetal anomalies, no prenatal care, selected medical and surgical complications, and those with incomplete medical records, 3191 cases remained for analyses by determination of odds ratios for obstetric outcomes, by chi 2 tests for significant differences and by adjustment for risk factors with stepwise logistic regression. RESULTS: Both increased maternal prepregnancy weight (body mass index) and increased maternal gestational weight gain were associated with increased risks of fetal macrosomia (p less than 0.0001), labor abnormalities (p less than 0.0001), postdatism (p = 0.002), meconium staining (p less than 0.001), and unscheduled cesarean sections (p less than 0.0001). They were also associated with decreased frequencies of low birth weight (p less than 0.001). The magnitude of the last was less than that of the other outcomes. CONCLUSIONS: Increased maternal weight gain in pregnancy results in higher frequencies of fetal macrosomia, which in turn lead to increased rates of cesarean section and other major maternal and fetal complications. Because these costs of increased maternal weight gain appear to outweigh benefits, weight gain recommendations for pregnancy warrant careful review. PMID- 1497039 TI - A prospective randomized clinical trial comparing two oxytocin induction protocols. AB - OBJECTIVE: Our objective was to compare the safety and efficacy of two accepted oxytocin induction protocols that differ in oxytocin dose increments. STUDY DESIGN: At the Carolinas Medical Center in Charlotte, North Carolina, 151 women with indications for induction of labor were prospectively randomized into one of two oxytocin induction protocols. Safety and efficacy of the two protocols were analyzed with two-tailed t tests and chi 2. RESULTS: Time from induction to establishment of a regular labor pattern was significantly shorter in the experimental group compared with the traditional group (p = 0.03). However, no significant difference was seen from onset of induction to time of delivery. Incidences of hyperstimulation were not significantly different between the two protocols, but there was a trend toward a higher incidence of fetal heart rate changes in the experimental group (p = 0.08). CONCLUSION: These data suggest that induction with larger dose increments will shorten time to adequate labor without an associated increase in uterine hyperstimulation or poor neonatal outcome. The differences in heart rate changes are concerning and merit further investigation. If confirmed by further studies, an increased risk of cord compression could outweigh the benefit of a faster onset of contractions. PMID- 1497040 TI - Intrauterine pressure and fluid absorption during continuous flow hysteroscopy. AB - OBJECTIVES: Our objectives were to document the causes of fluid absorption during continuous flow hysteroscopy and to determine under which operative conditions fluid overload may occur. STUDY DESIGN: Fifteen patients underwent operative hysteroscopy with 2% ethanol solution for uterine distention. Absorption of fluid was measured by blood alcohol, sodium, osmolarity, and hematocrit. Intrauterine pressures were measured with an obstetric pressure catheter. RESULTS: Alcohol absorption was noted in one patient during a myoma resection. Two additional patients, not in the study, had fluid absorption after partial perforations of the uterus. Under normal operative conditions there were no changes in sodium, osmolarity, or hematocrit. Intrauterine pressures ranged from 45 to 75 mm Hg. Experimental pressures of greater than 200 mm Hg were not associated with fluid absorption. CONCLUSIONS: Intravasation of fluid may occur through open uterine venous channels with extensive resections and under low pressures in the presence of unrecognized perforations. PMID- 1497041 TI - Obesity and lower urinary tract function in women: effect of surgically induced weight loss. AB - OBJECTIVE: The subjective and objective effects of massive weight loss on lower urinary tract function in morbidly obese women were examined. STUDY DESIGN: Thirteen subjects underwent a comprehensive evaluation of lower urinary tract function before and 1 year after surgically induced weight loss. RESULTS: We demonstrated significant improvements in lower urinary tract function after weight loss. Of 12 subjects who complained of incontinence before surgery only three complained of incontinence (p = 0.004) and only one requested treatment after weight loss. Objective and subjective resolution of both stress and urge incontinence was documented. Statistically significant changes were seen in measures of vesical pressure, the magnitude of bladder pressure increases with coughing, bladder-to-urethra pressure transmission with cough, urethral axial mobility, number of incontinence episodes, and the need to use absorptive pads. CONCLUSION: Weight reduction is desirable for obese women complaining of urinary incontinence and may obviate the need for further incontinence therapy. PMID- 1497042 TI - The incidence of genital prolapse after the Burch colposuspension. AB - OBJECTIVE: Our objective was to determine the incidence of postoperative genital prolapse after the Burch colposuspension and to identify risk factors for the development of subsequent prolapse. STUDY DESIGN: The charts of 131 patients who had a Burch colposuspension performed by the senior author (S.L.S.) between 1977 and 1986 were reviewed at the Urodynamic Unit of St. George's Hospital, London. Emphasis was placed on the degree of genital prolapse on clinical examination and whether further surgery was required to correct the prolapse. RESULTS: Thirty five patients (26.7%) required a total of 40 operations to correct genital prolapse after colposuspension. At 20 operations, more than one procedure was required to correct combined prolapse. The patient's age, weight, parity, menopausal status, and prior pelvic surgery did not affect the incidence of postoperative prolapse. The only preoperative risk factor identified was the presence of a large cystocele. CONCLUSION: Postoperative genital prolapse is a significant complication of the Burch colposuspension. It is unclear whether this is due to a disruption of the vaginal axis or to an intrinsic weakness of the pelvic floor in these women. PMID- 1497043 TI - Evaluation of pretreatment transvaginal ultrasonography in the management of patients with endometrial carcinoma. AB - OBJECTIVE: The objective of this study was to evaluate the usefulness of pretreatment assessment with ultrasonography in patients with endometrial carcinoma. STUDY DESIGN: Fifty patients with endometrial carcinoma diagnosed by endometrial biopsy or curettage were studied before hysterectomy, bilateral salpingo-oophorectomy, and selected lymph node sampling. Ultrasonographic criteria for determination of tumor grade, depth of myometrial invasion, uterine volume, and tumor volume were established. Tumor grade was compared with preoperative and postoperative pathologic diagnoses, depth of invasion was compared with postoperative pathologic evaluation, and uterine volume and tumor volume were compared with postoperative evaluation of tumor grade and depth of invasion. Data were analyzed by chi 2 testing, and, where appropriate, sensitivity, specificity, and accuracy of the ultrasonographic measurements were determined. RESULTS: The following statistically significant correlations (p less than or equal to 0.05) were found. Ultrasonography predicted tumor grade as accurately as preoperative pathologic evaluation did. Depth of invasion less than or equal to 50% or greater than 50% significantly correlated. Uterine volume less than or equal to 200 ml predicted less than or equal to 50% depth of invasion 28 of 32 times. Uterine volume greater than 500 ml was noted in six cases; five of these had grade 2 or 3 tumor and four had depth of invasion greater than 50%. Tumor volume less than or equal to 20 ml predicted a grade 1 tumor in 25 of 39 cases and depth of invasion less than or equal to 50% in 34 of 39 cases. Tumor volume greater than 20 ml correlated with a grade 2 or 3 tumor in 11 of 11 cases and a depth of invasion greater than 50% in seven of 11 cases. In 25 grade 1 tumors diagnosed postoperatively by pathologic study, none was associated with a tumor volume greater than 20 ml. CONCLUSION: Pretreatment ultrasonographic measurements should be of value in the management of patients with endometrial carcinoma. PMID- 1497044 TI - The treatment of pelvic soft tissue radiation necrosis with hyperbaric oxygen. AB - OBJECTIVE: The purpose of this study was to examine the therapeutic effects of hyperbaric oxygen on radiation-induced soft tissue necrosis in patients who previously received treatment for a gynecologic malignancy. STUDY DESIGN: Fourteen patients whose necrotic wounds failed to heal after 3 months of conservative therapy were enrolled in a prospective observational study. Outcome of hyperbaric oxygen treatment was measured by resolution of necrosis. RESULTS: Fourteen patients underwent 15 courses of hyperbaric oxygen treatments. All those with radiation necrosis of the vagina alone or in association with rectovaginal fistula had complete resolution of necrosis with hyperbaric oxygen. Only one treatment failure occurred. CONCLUSION: Hyperbaric oxygen is a safe, effective, and well-tolerated treatment for radiation-induced soft tissue necrosis. PMID- 1497045 TI - The incidence of cerebral palsy. AB - The clinician is often held responsible for obstetric events that are suspected of being related to cerebral palsy. To review the incidence of cerebral palsy and to aid the clinician in this situation, a search of published studies was conducted. Composite rates of cerebral palsy in different birth weight infants and cerebral palsy with and without serious mental retardation were calculated. The cumulative incidence rate at the age of 5 to 7 years was 2.7 cases of cerebral palsy for 1000 birth cohorts. Approximately 36% of all cerebral palsy occurred in the infant less than 2500 gm. Serious mental retardation (intelligence quotient less than 50) accompanied cerebral palsy approximately 30% of the time for the term infant and 18% of the time when the infant was less than 2500 gm. On the basis of a past estimation that 70% of cerebral palsy is of antepartum or unknown origin, the term infant at risk for intrapartum-attributed cerebral palsy may be about 1 in 2000 term births. PMID- 1497046 TI - Home uterine activity monitoring in France: a randomized, controlled trial. AB - OBJECTIVES: We assessed the effectiveness of ambulatory tocodynamometry in reducing the preterm delivery rate in women at risk of preterm delivery such as women with risk factors and women previously hospitalized and discharged. STUDY DESIGN: In four public maternity units these women were randomly allocated to two groups: 84 had home uterine activity monitoring and daily midwife contact and 84 were given the standard care for high-risk women, which generally includes home visits by community midwives. RESULTS: The proportion of deliveries before 37 weeks' gestation was slightly higher in the monitored group than in the control group (32% vs 22%). The corresponding odds ratio was 1.7 (95% confidence interval: 0.9 to 3.5). CONCLUSION: Although the sample was small, these results suggest that home uterine activity monitoring was probably not beneficial to the population studied, or at least that any benefit would have been too small to justify extending this monitoring in this high-risk population. PMID- 1497047 TI - Maternal hyperoxygenation in the treatment of intrauterine growth retardation. AB - OBJECTIVE: In the current study the efficacy of maternal hyperoxygenation on growth-retarded fetuses was evaluated. STUDY DESIGN: Thirty-six pregnant women with intrauterine growth retardation were studied. The patients were divided in oxygen-treated (n = 17) and untreated (n = 19) groups. Doppler analysis of the fetal circulation was performed on the arrival to the hospital, after 12 hours, and thereafter on alternate days until delivery. Fetal blood was sampled by cordocentesis for immediate blood gas analysis at entrance to the study and the day of delivery. RESULTS: Significant improvement in Doppler flow patterns in treated patients were found when compared with untreated women. The Doppler variations were associated with complementary modifications in fetal blood gas. These differences resulted in a significant modification in perinatal mortality with an incidence of 29% and 68% (p less than 0.01) in treated and untreated groups, respectively. CONCLUSION: Our data suggest a benefit of maternal hyperoxygenation in the treatment of fetal growth retardation. PMID- 1497048 TI - Behavioral treatment of menopausal hot flushes: evaluation by ambulatory monitoring. AB - OBJECTIVES: We attempted to develop an effective behavioral treatment for menopausal hot flushes and to determine the active behavioral components of this procedure. STUDY DESIGN: Thirty-three women with frequent menopausal hot flushes were randomly assigned to receive eight sessions of training in paced respiration, muscle relaxation, or alpha-wave electroencephalographic biofeedback (placebo control). Hot flushes were objectively measured by means of 24-hour ambulatory monitoring of the sternal skin conductance level. RESULTS: Subjects undergoing paced respiration had significant reductions in hot flush frequency and respiration rate, as well as increases in tidal volume. CONCLUSION: Paced respiration training may be a useful treatment alternative for the reduction of hot flushes in women who cannot tolerate hormone replacement therapy. PMID- 1497049 TI - Increased lipolytic activity and high ratio of free fatty acids to albumin in sera from women with preeclampsia leads to triglyceride accumulation in cultured endothelial cells. AB - OBJECTIVE: The null hypothesis of this study was that the triglyceride accumulation in endothelial cells exposed to sera from preeclamptic women was determined by the presence of triglyceride-rich lipoproteins in the sera. STUDY DESIGN: The accumulation of triglycerides in cultured endothelial cells was studied using incorporation of tritiated glycerol. RESULTS: Triglyceride-rich lipoproteins in the patient sera contributed little to the endothelial triglyceride accumulation. However, sera from preeclamptic women were found to have a higher molar ratio of free fatty acids to albumin compared with sera from women with normal pregnancies (1.6 +/- 0.5 vs 0.9 +/- 0.4, respectively, p less than 0.025). In addition, sera from preeclamptic women, compared with sera from normal pregnancies, showed enhanced lipolytic activity (release of free fatty acids 0.85 +/- 0.29 vs 0.17 +/- 0.16 mmol/ml per 24 hours, respectively; p less than 0.025) that further increased the free fatty acids/albumin ratio. CONCLUSION: Sera from preeclamptic women have both a higher ratio of free fatty acids to albumin and increased lipolytic activity, resulting in enhanced endothelial uptake of free fatty acids, which are further esterified into triglycerides. PMID- 1497050 TI - Use of the fetal chest in estimating fetal weight. AB - OBJECTIVE: This study was designed to develop formulas using the chest circumference instead of the abdominal circumference for estimating fetal weight. STUDY DESIGN: Ultrasonographic measurements of the chest circumference, biparietal diameter, abdominal circumference, humeral length, and femoral length were obtained in 75 term fetuses of uncomplicated pregnancies within 24 hours of delivery. Three equations for fetal weight estimation that used the chest circumference, instead of the abdominal circumference, in combination with the biparietal diameter or the humeral length were developed by regression analysis. RESULTS: The average mean errors of fetal weight estimation for these equations vary from 7.1% to 7.6%. CONCLUSIONS: These equations may be used in predicting the birth weight when the fetal abdomen is altered by certain fetal abnormalities. PMID- 1497051 TI - A comparison of circulating hormone levels in postmenopausal women receiving hormone replacement therapy. AB - Seventeen postmenopausal subjects were randomized into this comparative study of esterified estrogen 0.625 mg (Estratab), esterified estrogen 0.625 mg plus 1.25 mg methyltestosterone (Estratest H.S.), or conjugated estrogen 0.625 mg (Premarin). Sixteen subjects completed the study in which plasma hormone concentrations of estrone and estradiol were assessed at various time points. There were no significant differences among the treatment groups. PMID- 1497052 TI - Prenatal diagnosis of human parvovirus B19 in nonimmune hydrops fetalis by polymerase chain reaction. AB - OBJECTIVE: Nonimmune hydrops fetalis is a potentially lethal condition reflecting the clinical manifestation of several pathologic processes. Recently maternal infection by human parvovirus B19 has been reported to result in nonimmune fetal hydrops. We sought to develop a rapid and sensitive test to detect the presence of this agent in utero. STUDY DESIGN: Using a cloned isolate of the virus, we developed an assay based on enzymatic amplification of a segment of the human parvovirus B19 genome that allows direct detection of this agent in samples of fetal blood and amniotic fluid. RESULTS: The method detected as few as 100,000 genome equivalences and was specific for the viral genome alone. We used this assay to evaluate nine fetuses initially seen with nonimmune hydrops. Three cases were found to be positive for the human parvovirus B19 genome. CONCLUSION: The method is powerful in that it is rapid, sensitive, and simple. This assay may have general applicability in evaluation of nonimmune hydrops and in documentation of the natural history of fetal human parvovirus infections. PMID- 1497053 TI - Angina and normal coronary arteries in women: gynecologic findings. AB - OBJECTIVES: Our aim was to evaluate the hypotheses that women with severe angina and normal coronary arteries (syndrome X) have an increased incidence of hysterectomy and show a positive cardiac response to 17 beta-estradiol replacement therapy. STUDY DESIGN: The gynecologic histories of 30 women with syndrome X were determined. Anginal and 17 beta-estradiol insufficiency symptoms were recorded daily for 1 month. Subsequently, 20 of the women underwent hyperemic response testing before and after 2 months of estrogen replacement therapy. Hyperemic response results were compared with those of 12 asymptomatic post-menopausal women not receiving estrogen replacement therapy. Symptoms were recorded daily during estrogen replacement therapy. RESULTS: A total of 18 women (60%) underwent hysterectomy. All were experiencing hot flushes. Hyperemic response was diminished in women with syndrome X compared with controls. Hyperemic response increased and anginal symptoms decreased during estrogen replacement therapy. CONCLUSION: The incidence of hysterectomy was increased and estrogen replacement therapy alleviated cardiac symptoms and enhanced hyperemic response in a group of women with syndrome X. PMID- 1497054 TI - Effects of danazol at the immunologic level in patients with adenomyosis, with special reference to autoantibodies: a multi-center cooperative study. AB - OBJECTIVE: We attempted to evaluate the effects of danazol on autoantibodies, in particular, to phospholipids, and on the immune system in patients with adenomyosis. STUDY DESIGN: Forty-two patients with adenomyosis who had high titers of autoantibodies were randomly chosen, and they received 400 mg/day of danazol for 4 months (n = 22) or underwent hysterectomy (n = 20). RESULTS: Among the six autoantibodies we investigated, the incidence of antiphosphatidylinositol immunoglobulin G was the highest (42.9%), followed by antiphosphatidylglycerol immunoglobulin G (38.1%). The autoantibody titers decreased with time and were comparable to the control values 16 weeks after treatment in both groups. Total serum levels of immunoglobulin G and M were high before treatment, but immunoglobulin M levels decreased significantly in week 8 during treatment with danazol, whereas C4 levels increased and C3 levels decreased with danazol. CONCLUSION: Danazol has an inhibitory effect on the autoimmunologic response associated with adenomyosis. PMID- 1497055 TI - Serial measurements of platelet angiotensin II binding in two patients with hypertension in pregnancy: case reports. AB - Serial estimations of platelet angiotensin II binding were made in two patients with hypertension developing in the third trimester of pregnancy. The fall in platelet angiotensin II binding that is seen in normotensive pregnancy did not occur in these two patients. PMID- 1497056 TI - Resident research in obstetrics and gynecology: development of a program with comparison to a national survey of residency programs. AB - OBJECTIVE: The objective of this report is to describe our recently established resident research program and to compare this program with those of other obstetrics and gynecology residency training programs in the United States. STUDY DESIGN: The components of our program are described. Data for comparison from other programs were obtained from questionnaires, phone follow-up and the Directory of Obstetrics and Gynecology Residency Programs of the Council on Resident Education in Obstetrics and Gynecology. RESULTS: We initiated a residency research program in 1987 with acceptable projects defined, a time for completion of manuscripts established, and a Resident Research Day organized with presentation of articles, critique by a guest speaker, and an awards banquet. Nationally, less than 60% of residency programs have research requirements. Of the 208 programs responding to the written questionnaire 86% of programs associated with a university required research compared with 10% of community based residency programs. CONCLUSION: While more than a third of residency programs in obstetrics and gynecology do not have resident research programs, the trend is for programs to establish research as a required portion of training. An outline of a recently established program is provided. PMID- 1497057 TI - Nonimmune fetal hydrops caused by bilateral type III congenital cystic adenomatoid malformation of the lung at 17 weeks' gestation. AB - Type III congenital cystic malformation of the lung with nonimmune hydrops and oligohydramnios was diagnosed at 17 weeks by ultrasonography. Massive fetal cardiac compression with probable associated left- and right-sided failure causing both the oligohydramnios and the ascites, respectively, was thought to be the underlying pathophysiologic mechanism of this unusual clinical presentation. Pathologic examination after termination of the pregnancy confirmed the prenatal diagnosis. PMID- 1497058 TI - Pregnancy complicated by chronic cardiomyopathy and an automatic implantable cardioverter defibrillator. AB - The dismal prognosis of dilated cardiomyopathy and its resulting tachyarrhythmias has recently been improved by technical advances such as the automatic implantable cardioverter defibrillator. We report a successful pregnancy in a patient with chronic cardiomyopathy and malignant tachyarrhythmias necessitating use of this device, with a documented defibrillator discharge and monitored fetal response. PMID- 1497059 TI - Repeated external cephalic version at term. AB - External version was performed three times in a patient at term because of spontaneous reversion to breech presentation. She was then delivered vaginally. Spontaneous reversion to breech presentation can be managed with additional external cephalic version procedures. PMID- 1497060 TI - Successful pregnancy outcomes after amniotic fluid embolism. AB - Two patients who survived cardiorespiratory arrest occurring in association with amniotic fluid embolism syndrome were seen during the subsequent pregnancy. Both had uneventful pregnancies and delivered at term without complications. These are the only case reports of pregnancy after amniotic fluid embolism, and they support a model of amniotic fluid embolism involving chemically abnormal amniotic fluid rather than an unusual sensitivity to normal amniotic fluid. PMID- 1497061 TI - Hepatotoxicity with the administration of nifedipine for treatment of preterm labor. AB - Nifedipine, a calcium channel blocker, is becoming increasingly popular as a tocolytic medication. Previous reports of hepatitis associated with nifedipine in the medical literature have been published. We present the first case reported of a patient with preterm labor treated with nifedipine who had development of a concurrent elevation in serum liver enzyme levels. PMID- 1497062 TI - Vaginal foreign body extraction by forceps: a case report. AB - Cases in which foreign bodies have been inserted into the vagina are uncommon but do occur. The technique and use of obstetric forceps for the extraction of an orange as a vaginal foreign body is described in this case report. Tucker-McLane forceps are the forceps of choice for this technique in this case. PMID- 1497064 TI - A case of hidradenitis suppurativa treated with gonadotropin-releasing hormone agonist and by total abdominal hysterectomy with bilateral salpingo-oophorectomy. AB - We report on a patient with hidradenitis suppurativa with premenstrual exacerbations, who was treated successfully with total abdominal hysterectomy and bilateral salpingo-oophorectomy combined with estrogen substitution. As a trial, she was initially treated successfully with a gonadotropin-releasing hormone agonist and subsequently a gonadotropin-releasing hormone agonist in combination with estrogen substitution. PMID- 1497063 TI - Leiomyomatosis peritonealis disseminata treated with a gonadotropin-releasing hormone agonist. A case report. AB - To our knowledge, this is the first report of documented growth regression of leiomyomatosis peritonei while the patient was receiving a gonadotropin-releasing hormone agonist. This further documents the role of gonadal steroids in the growth of this tumor. PMID- 1497065 TI - Autonomic nervous system regulation of baseline heart rate in the fetal lamb. AB - OBJECTIVE: We examined 29 chronically instrumented fetal lambs from 125 to 143 days' gestation to investigate the effects of fetal behavioral states and autonomic nervous system maturation on baseline fetal heart rate. STUDY DESIGN: Behavioral states were defined from electrocorticographic analysis as low-voltage fast activity or high-voltage slow activity. Decrease and increase in baseline fetal heart rate subsequent to administration of propranolol and methylatropine represented beta-sympathetic and parasympathetic activity. RESULTS: Baseline fetal heart rate decreased with gestation in both states, with steeper regression in low-voltage fast activity (p less than 0.001). Positive correlation was noted between gestational age and percent decrease baseline fetal heart rate in both states with steeper regression in high-voltage slow activity (p less than 0.001), and between gestational age and percent increase baseline fetal heart rate with steeper regression in low-voltage fast activity (p less than 0.001). Fetal heart rate beta-sympathetic and parasympathetic tones increased with age in both states, with elevation of beta-sympathetic tone in high-voltage slow activity and parasympathetic tone in low-voltage fast activity. CONCLUSION: Sympathetic and parasympathetic systems influence baseline fetal heart rate in these behavioral states and with age. PMID- 1497066 TI - Effects of sustained hypoxemia on the sheep fetus at midgestation: endocrine, cardiovascular, and biophysical responses. AB - OBJECTIVE: The purpose of our study was to examine the effects of induced hypoxia on endocrine, cardiovascular, and biophysical measurements of the ovine fetus at 0.6 (83 to 93 days) of gestation and to compare the fetal responses at this earlier gestation with those reported near term. STUDY DESIGN: Fourteen fetal sheep were studied (9 in the hypoxia group and 5 in the control group) at 0.6 of gestation during a 24-hour control period, 8 hours of either sustained hypoxemia or room air, and a 40-hour recovery period. RESULTS: Induced fetal hypoxemia resulted in a progressive lactic metabolic acidosis; however, all fetuses had recovered within 24 hours. The fetal endocrine response was variable with norepinephrine, the only measured hormone showing a significant hypoxia-related increase (p less than 0.05). Fetal heart rate and mean arterial blood pressure showed little hypoxia-induced change, although fetal heart rate was significantly increased over the first 2 hours (p less than 0.05). The percent time fetal breathing movements, electroocular activity, and nuchal muscle activity likewise showed little hypoxia-induced change. CONCLUSION: The cardiovascular and biophysical response of the preterm fetus to induced hypoxemia is thus much less pronounced than that of the older gestational-aged fetus; this difference may impact on survival and the success of antenatal assessment protocols. PMID- 1497067 TI - Intracellular calcium and the signaling mechanism of luteinizing hormone releasing hormone in rat granulosa cells. AB - OBJECTIVE: The purpose of these studies was to determine the source(s) of the increase in intracellular free calcium in response to luteinizing hormone releasing hormone in ovarian granulosa cells. STUDY DESIGN: Rat granulosa cells were cultured and loaded with fura-2-acetoxy-methyl ester, a fluorescent calcium indicator dye, and intracellular free calcium measured by microspectrofluorometry. The source of the luteinizing hormone-releasing hormone induced increase in intracellular Ca++ was investigated with various calcium channel blockers (verapamil, diltiazem, and nifedipine), high K+ buffer, and perifusion with media lacking Ca++. RESULTS: All three voltage-sensitive calcium channel blockers (10(-5) mol/L) tested were ineffective in blocking the luteinizing hormone-releasing hormone induced intracellular Ca++ increase. Treatment with high K+ buffer also had no effect. Perifusion with media lacking calcium resulted in a gradual loss of the luteinizing hormone-releasing hormone response, an effect that was accelerated by repeated stimulation with hormone. Transient replacement of extracellular Ca++ failed to restore the response but continued perifusion with Ca(++)-replete media allowed a luteinizing hormone releasing hormone response 10 minutes later. CONCLUSIONS: The luteinizing hormone releasing hormone induced intracellular Ca++ increase does not appear to result from the opening of voltage-sensitive or K(+)-dependent Ca++ channels. To the contrary, this response likely results from the release of Ca++, primarily from intracellular stores. PMID- 1497068 TI - Comparative analysis of normal and growth-retarded placentas with phosphorus nuclear magnetic resonance spectroscopy. AB - OBJECTIVE: Phosphorus 31 magnetic resonance spectroscopy studies were carried out on placentas from normal vaginal and elective cesarean deliveries without antenatal complications and from pregnancies complicated by intrauterine growth retardation of unknown cause to determine differences. STUDY DESIGN: Perchloric acid extraction was performed on frozen tissue, and quantitative analysis was carried out for well-resolved resonances representing adenosine triphosphate, sugar phosphate, inorganic phosphorus, diphosphoglycerate, glycerophosphorylethanolamine, and glycerophosphorylcholine. RESULTS: Adenosine triphosphate levels were highest in the growth-retarded group. There were significantly higher levels of sugar phosphate, diphosphoglycerate, and glycerophosphorylcholine in the placentas of the growth-retarded pregnancies compared with those from normal placentas. CONCLUSION: These differences may represent a response to hypoxia and an increase in the amount of blood in the placenta. The results demonstrate the utility of nuclear magnetic resonance spectroscopy for studying the pathology of abnormal placentas to gain a better understanding of the pathology and represent early steps toward in vivo spectroscopic studies of the placenta. PMID- 1497069 TI - Electrocortical activity, electroocular activity, and breathing movements in fetal sheep with prolonged and graded hypoxemia. AB - OBJECTIVE: Our objective was to determine the effect of a prolonged and graded reduction in fetal arterial oxygen saturation on electrocortical activity and associated biophysical variables. STUDY DESIGN: Fourteen unanesthetized fetal sheep were studied between 126 and 135 days' gestation with continuous monitoring of electrocortical and electroocular activity and breathing movements, during a 24-hour control period, and subsequently during 4 days of prolonged and graded hypoxemia induced by progressively lowering the maternal inspired oxygen concentration. RESULTS: Graded reduction in fetal arterial oxygen saturation resulted in little change in arterial pH until close to 30% when metabolic acidemia was apparent. The incidence of low-voltage electrocortical activity, electroocular activity, and breathing movements were marginally decreased with hypoxemia alone; however, a significant decrease was not apparent until associated with the onset of fetal acidemia. CONCLUSION: Hypoxemia of a chronic nature must approach the level at which acidemia becomes apparent before a marked change in fetal behavioral activity is noted. PMID- 1497070 TI - Subtherapeutic doses of magnesium sulfate do not inhibit preterm labor. PMID- 1497071 TI - An association between placental location and nuchal cord occurrence. PMID- 1497072 TI - Menopausal patient considerations. PMID- 1497073 TI - Daily commuting and preterm birth rate. PMID- 1497074 TI - Imaging of the levonorgestrel implantable contraceptive device. PMID- 1497075 TI - Special issue of cross-cultural perspectives in occupational therapy. PMID- 1497076 TI - What occupational therapists can do to eliminate racial barriers to health care access. AB - Now is the time for the American Occupational Therapy Foundation and individual institutions of higher education that house occupational therapy programs to step into the leadership vacuum created by this issue. We must not only design new minority scholarships programs, but also be prepared to defend existing ones. Given the current confusion and fluctuations of opinion on this issue, what is policy now may not be policy after the next presidential election. The Council on Ethical and Judicial Affairs of the AMA has recommended recruiting minority students, procuring greater scholarship assistance, and pursuing affirmative action in school admission and faculty hiring as strategies for eradicating racial barriers to equal access to health care. As an allied medical profession, we must follow the Council's lead. PMID- 1497077 TI - A cross-cultural test of the validity of occupational therapy assessments with patients with schizophrenia. AB - The validity and use of psychosocial assessments in occupational therapy are ongoing concerns (Moyer, 1984) and were the focus of this study. Fifty African patients with schizophrenia and 10 nondysfunctional African volunteers took an an assessment battery that included the Schroeder, Block, Campbell Adult Psychiatric Sensory Integration Evaluation (SBC) (Schroeder, Block, Trottier, & Stowell, 1978), a daily activity, work, and leisure activity interview based on the Model of Human Occupation (Kielhofner, 1985), and a culture-specific test of functional performance. Data on subjects' psychiatric histories and demographics were collected. Rationale for the assessments used, methods for devising the functional assessment, methods and procedures for data collection, and analysis are presented. A stronger relationship was found to exist between subjects' performances on the SBC and the functional activity test than between interviews based on the Model of Human Occupation and the functional activity test, both for patients and for the whole sample. All assessments were found to differentiate between patients and nonpatients, although the SBC was the best discriminator. Among psychiatric history variables, the strongest relationships were between measures of seriousness of illness and both the SBC and functional activity assessment. The most effective way to measure performance dysfunction and seriousness of illness in persons with schizophrenia was to measure the underlying sensorimotor impairment or to use a culture-specific test of functional performance. PMID- 1497078 TI - Managing chronic illness: an immigrant woman's acquisition and use of health care knowledge. AB - As occupational therapists increasingly encounter a multicultural clientele, there is growing interest in the influence of a person's culture on his or her interactions with the environment. This paper presents a case study of a Chinese Canadian immigrant woman with rheumatoid arthritis. The case study illustrates how the subject's family, community networks, and workplace, coupled with the occupational therapy clinical setting, intermingled to shape the daily management of her illness. The case material focuses on the subject's acquisition and use of different types of health care knowledge as she responds to her illness. It shows that the subject's experiences and management decisions about her health are closely linked to the material and social conditions of her life as a working class immigrant woman. This article suggests that attention needs to be paid to the broader systems of the environment in understanding the responses of immigrant women to occupational therapy, rather than on the cultural distinctiveness of the clients. PMID- 1497079 TI - Internal-external control and temporal orientation among southeast Asians and white Americans. AB - This study examined ethnic group differences with the use of the Model of Human Occupation (Kielhofner, 1985b). Three groups--immigrants from Thailand, immigrants from Cambodia, and white Americans--were contrasted on two constructs- internal versus external control and temporal orientation. The study attempted to identify whether nonpatient subjects have an internal locus of control and a strong future orientation, as the Model of Human Occupation would predict. No differences were found with the use of the Internal-External Scale (Rotter, 1966). The Thai and white Americans differed significantly on the Time Reference Inventory (Roos & Albers, 1965b). The Thai selected more items referring to the past, and the white Americans chose more statements applying to the present. There were no differences for past or future time extensions between groups. All the groups had a greater past extension than future extension. It was proposed that a larger future time perspective was not a requisite for functional temporal adaptation. PMID- 1497080 TI - Culturally competent occupational therapy in a diversely populated mental health setting. AB - Cultural sensitivity is a crucial component of health care provision, particularly in psychiatric settings. As society becomes more multicultural, it is essential for occupational therapists to continue to develop cultural competence, which is defined in this paper as an awareness of, sensitivity to, and knowledge of the meaning of culture. At San Francisco General Hospital, an innovative multicultural model consisting of special focus programs is used. The key to the success of such programs is a culturally competent professional staff. PMID- 1497081 TI - An occupational therapy life skills curriculum model for a Native American tribe: a health promotion program based on ethnographic field research. AB - A unique, nontraditional occupational therapy role focusing on primary prevention, community health promotion, and enhancement for a nonpatient population is examined. The purpose of this ongoing consultancy project was to develop a series of life skills and prevocational programs for an ethnic population of native Americans from elementary school through high school and post-secondary adulthood levels in British Columbia, Canada, from 1986 to 1990. This consultancy evolved from a philosophy of renewing and preserving the culturally distinct ethnic heritage and tribal integrity of this native American community. Knowledge about sociocultural systems theory, anthropology, and developmental cognitive-behavioral learning theories are combined with ongoing clinical experience in psychosocial occupational therapy practice and consultancy principles to develop life skills and an educational, community-based prevention/wellness educational program model. Subsequent modifications of the original model, with consultancy recommendations for implementation of future programs, are based on tribal members' feedback and concerns elicited with psychosocial and ethnographic interviewing techniques during villager community meetings. The replicability of this primary prevention and wellness life skills program model offers numerous possibilities for occupational therapists to develop similar programs within the cultural contexts and perceived needs of specific ethnic groups in other nontraditional community-based settings. PMID- 1497082 TI - Culture, theory, and the practice of occupational therapy in New Zealand/Aotearoa. AB - In the context of contemporary New Zealand, this paper discusses the need for occupational therapy to substantiate its claims of being a holistic profession with particular reference to the Maori, the indigenous people of New Zealand (referred to by the Maori as Aotearoa). In this era of accountability and consumer choice, occupational therapists need to more effectively meet the cultural needs of their clients through an understanding of both the material and nonmaterial aspects of their cultures. However, for New Zealand occupational therapists, cultural sensitivity is not enough to contribute to changing the diminished life chances of the Maori. It is proposed in this paper that the Model of Human Occupation (Kielhofner, 1985; Kielhofner & Burke, 1980), when combined with the work of radical community educators such as Freire (1972), could provide the sociopolitical dimension to New Zealand practice. The Model of Human Occupation is examined in light of current occupational therapy practice in New Zealand. It is argued that this model, when accompanied by a broader understanding of the sociopolitical processes informing monoculturalism, could be seen as a suitable framework for understanding cultural differences in New Zealand and could assist in the move toward providing culturally appropriate occupational therapy for indigenous peoples such as the Maori. PMID- 1497083 TI - Cross-cultural occupational therapy: a critical reflection. AB - In the Netherlands, Dutch health care professionals, including occupational therapists, are confronted with a growing number of patients whose cultural backgrounds differ from theirs. Acknowledging this influx, the Dutch government allocated a grant for educating occupational therapy students on cross-cultural care. This paper summarizes the information we collected from a survey of Dutch occupational therapists on treatment of immigrants and briefly describes the eight educational tools we developed for the two occupational therapy curricula. Two of these tools are described fully--first, a critical essay on the white middle-class values and norms that underlie occupational therapy theory and practice, and second, the guidelines for developmental policies to use in the treatment of immigrant patients. Case studies illustrate how the values of our profession create obstacles to cross-cultural care. PMID- 1497084 TI - Strategies for the development of occupational therapy in the Third World. PMID- 1497085 TI - The Handy Exerciser. PMID- 1497086 TI - Glomerular epithelial cells synthesize endothelin peptides. AB - Glomerular mesangial and endothelial cells have been reported to synthesize and secrete endothelin-1 (ET-1). Whether glomerular epithelial cells (GEC) have the ability to synthesize ET-peptides is not known. Employing immunocytochemistry we report that the GEC in vitro constitutively express ET-1 and ET-3. ET-1 synthesis by the GEC was further confirmed by detection of a specific 2.3kb mRNA that hybridizes with rat prepro ET-1 genomic DNA on Northern blot analysis. ET-1 is secreted into the medium in a time-dependent manner as measured by radioimmunoassay and radiobinding assay. Synthesis of endothelin peptides by the GEC may have important implications in the pathogenesis of glomerular diseases where GEC injury figures prominently. PMID- 1497087 TI - Altered expression of a structural protein (fodrin) within epithelial proliferative disease of the breast. AB - Although certain histopathologic patterns of epithelial proliferative breast disease are well established as indicating an increased relative risk for the subsequent development of mammary carcinoma, the biologic characterization of these changes is not known. One evident histologic characteristic of epithelial hyperplasia is the partial or complete loss of normal cellular polarity. Nonerythroid spectrin (fodrin) is a structural protein whose function is related to maintenance of cellular polarity. By immunohistochemical analysis, normal breast luminal epithelia contain fodrin confined to a characteristic basolateral distribution. Proliferative breast disease of the common type partially loses this polarized distribution of fodrin; fodrin immunoreactivity is not limited to a basolateral location but is present around the cell membrane and is inconsistently present at luminal interfaces. Whether this change in distribution of fodrin is a permissive event in the development of proliferative disease or merely an associated finding is not known. PMID- 1497089 TI - In vivo effects of endotoxin on intraepithelial mucosubstances in rat pulmonary airways. Quantitative histochemistry. AB - Bacteria-induced bronchopneumonias are often characterized by an influx of neutrophils and excess mucus in pulmonary airways. This study determined how endotoxin, a component of gram-negative bacteria and a potent inflammatory agent, affects the ultrastructure of the mucociliary apparatus and the amount of stored intraepithelial mucosubstances in the main axial airways within the lung. Rats were intranasally instilled, once a day for 3 days, with endotoxin or saline (controls). Animals were sacrificed 1, 2, or 7 days after the last instillation. Microdissected intrapulmonary axial airways (generations 8-11) from the right caudal lobes of infusion-fixed lungs were processed for light and electron microscopy. Morphometric techniques were used to determine the volume densities (Vs) of histochemically stained intraepithelial mucosubstances and numerical densities of airway epithelial cells. There were marked increases, compared with controls, in the amount of intraepithelial mucosubstances in the intrapulmonary axial airways at generations 8 and 11 in the right caudal lobes from endotoxin instilled rats sacrificed 1, 2, and 7 days after the last instillation. There were significantly greater numbers of surface epithelial cells per length of basal lamina (i.e., hyperplasia) in endotoxin-exposed airways compared with airways from controls. This endotoxin-induced hyperplasia was due primarily to an increase in the number of mucus-secretory cells, which in endotoxin-exposed epithelium were columnar and contained numerous, large confluent, electronlucent, secretory granules composed of acidic and neutral glycoproteins. In contrast, secretory cells in airway epithelium from controls were cuboidal and contained small discrete, electron-dense, granules composed of only neutral glycoproteins. The numbers of ciliated cells and basal cells were similar in both control and endotoxin-exposed epithelium. Only endotoxin-exposed epithelium, however, contained atypical epithelial cells with numerous basal bodies, few cilia, and few apical secretory granules. These results indicate that repeated airway instillations of endotoxin induce an increase in the amount of intraepithelial mucosubstances, secretory cell hyperplasia, and excess luminal mucus in pulmonary airways. Therefore, endotoxin released from gram-negative bacteria may be partially responsible for the structural alterations, in the airway surface epithelium, which result in the excess luminal mucus observed in bacteria-induced bronchopneumonias. PMID- 1497090 TI - Recombinant interleukin-6 inhibits the growth of rat mesangial cells in culture. AB - Murine recombinant interleukin-6 (IL-6) inhibited [3H]thymidine uptake by cultured rat mesangial cells in a dose-dependent manner in the presence of 0.5% fetal bovine serum (FBS). The inhibitory effect of IL-6 on the growth of mesangial cells was also confirmed by a change in cell numbers. In the presence of increased concentrations of FBS (5% or 10%), the effect of IL-6 was not prominent. IL-6 showed no effects on intracellular Ca2+ levels of mesangial cells. IL-6 gene expression was rapidly induced in the "quiescent" mesangial cells by exposure to 20% FBS. These observations support the premise that IL-6 is synthesized in mesangial cells and inhibits the growth of mesangial cells in an autocrine manner. PMID- 1497088 TI - Detection of the t(14;18) at similar frequencies in hyperplastic lymphoid tissues from American and Japanese patients. AB - Follicular lymphoma shows a wide geographic variation in incidence, occurring more frequently in the U.S. than in Japan. A translocation involving the bcl-2 gene on chromosome 18 and the immunoglobulin heavy chain gene on chromosome 14 is frequently found in follicular lymphomas and is believed to play a critical role in the pathogenesis of these tumors. Recently, bcl-2/IgH rearrangements have been detected in reactive lymphoid tissue obtained from European patients, indicating that such rearrangements occur at some low but measurable background rate. In non malignant tissues, the polymerase chain reaction was used to study the frequency of bcl-2/IgH rearrangements in reactive lymphoid tissue obtained from American and Japanese patients to find out whether geographic variation in the incidence of follicular lymphoma was caused by differences in sporadic occurrence of the t(14;18). We found such rearrangements in 5 of 15 American hyperplastic tonsils and lymph nodes and 5 of 10 Japanese tonsils, an incidence close to that previously seen in European patients. These data suggest that the background incidence of such rearrangements is similar in all populations, regardless of the incidence of follicular lymphoma. PMID- 1497091 TI - Cytokine-induced neutrophil-derived interleukin-8. AB - During acute inflammation, the first line of cellular response for host defense is the neutrophil. In addition to the historic role of the neutrophil as a phagocyte, recent studies have identified this cell as an important source of a number of cytokines. In this study, we provide evidence that the neutrophil is a significant source of interleukin-8 (IL-8). Neutrophils freshly isolated from whole blood were not found to constitutively express IL-8 mRNA. In contrast, when these leukocytes were cultured on plastic they were activated, leading to the significant expression of de novo steady-state levels of IL-8 mRNA. In addition, when neutrophils were treated with cycloheximide, there was evidence for "superinduction" of steady-state levels of IL-8 mRNA and inhibition of antigenic IL-8 production. Neutrophils were subsequently stimulated with lipopolysaccharide (LPS), tumor necrosis factor-alpha, or interleukin-1-beta and were found to express IL-8 mRNA and antigen in both a time- and dose-dependent manner. Furthermore, neutrophils stimulated with traditional chemotactic/activating factors, such as the split product of the fifth component of complement (C5a), formylmethionyleucylphenylalanine (fMLP), and leukotriene B4 (LTB4) in a dose dependent manner did not produce significant antigenic IL-8, as compared with unstimulated controls. In contrast, when neutrophils were exposed to either of these neutrophil agonists in the presence of LPS, the production of antigenic IL 8 was significantly elevated, as compared with either of the stimuli alone, suggesting a synergistic response. These data would suggest that the neutrophil can no longer be viewed as only a phagocyte or warehouse for proteolytic enzymes, but is a pivotal effector cell that is able to respond to mediators in its environment and generate cytokines. This latter neutrophil response may be important for either the elicitation of additional neutrophils or to orchestrate the conventional immune response at sites of inflammation. PMID- 1497092 TI - Ultrastructural immunohistochemical localization of polyclonal IgG, C3, and amyloid P component on the congo red-negative amyloid-like fibrils of fibrillary glomerulopathy. AB - Renal biopsies from seven patients with Congo red-negative amyloid-like fibrillary glomerulopathy (FGP) were examined by protein A gold immuno-electron microscopy. Ultrastructurally, the fibrils in all cases exhibited positive immunostaining for IgG, both Ig light chains, C3, and amyloid P component (AP), but did not show positive immunostaining for glomerular basement membrane (GBM) associated proteins (collagen type IV and heparan-sulfate proteoglycans) or microfibril-associated proteins (fibronectin and fibrillin). In a triple-label study, AP and IgG were colocalized along the same fibril, whereas the gold probes for the detection of collagen type IV were absent. The results suggest that the fibrils are comprised of polyclonal IgG and C3 that bind AP. AP was immunolocalized sparsely but regularly along the lamina rara interna of normal GBM. AP was absent in the fibrils in a case of diabetic glomerulopathy, was scattered randomly without specificity for the electron-dense deposits in the GBM of membranous glomerulopathy, and lined up regularly along the fibrils in amyloid deposits. FGP is an entity in which the fibrils bind AP but lack the beta-pleated sheet structure necessary for Congo red staining that is typical of amyloid. PMID- 1497094 TI - Effect of serum amyloid P component level on transthyretin-derived amyloid deposition in a transgenic mouse model of familial amyloidotic polyneuropathy. AB - To elucidate the pathogenesis of amyloid deposition associated with familial amyloidotic polyneuropathy (FAP), we developed several transgenic mouse lines carrying the human mutant transthyretin (TTR) gene. We found that human TTR and mouse serum amyloid P component (SAP) are deposited as amyloid in tissues of these mouse lines. Because SAP is a major acute-phase reactant in mice, we asked whether repeated injections of Escherichia coli lipopolysaccharide (LPS) would enhance the amyloid deposition in one of these transgenic mouse lines. During the course of repeated LPS injections, serum levels of SAP in the transgenic mice remained between severalfold to about 50-fold higher than seen in the absence of stimulation. As no significant difference was detected in the onset, progression, and tissue distribution of TTR-derived amyloid (ATTR) deposition between the LPS stimulated and unstimulated transgenic mice, the induction of SAP synthesis by acute inflammation probably does not affect the onset and extent of ATTR deposition. PMID- 1497093 TI - Brain microvascular smooth muscle and endothelial cells produce granulocyte macrophage colony-stimulating factor and support colony formation of granulocyte macrophage-like cells. AB - Granulocyte-macrophage colony-stimulating factor (GM-CSF) is a potent stimulator of macrophages and neutrophils and plays a role in inflammatory diseases. In this article, we report that mouse brain-derived microvascular smooth muscle cells (SM) and endothelial cells (En) in coculture with splenocytes support the colony proliferation of immature granulocyte-macrophage-like (GM) cells. Unstimulated SM and En cells release GM-CSF as shown by ELISA assay and SM expresses mRNA for GM CSF by polymerase chain reaction (PCR). Stimulation of SM and En by a nonspecific activator (lipopolysaccharide) results in upregulation of GM-CSF production. GM colonies cannot be grown on cultured astrocytes or on extracellular matrix alone prepared from smooth muscle or endothelium. However, colonies form on the extracellular matrix and on astrocytes, either in the presence of SM- or En conditioned medium or after the addition of recombinant GM-CSF. The GM cells are positive for nonspecific esterase, peroxidase, and MAC-1 markers but are negative for FC gamma receptors and for Thy 1.2, CD8, CD4, MHC class II, and Asialo GM1 markers. These observations emphasize the possibility for active participation of brain microvasculature SM and En in acute inflammatory reactions of the central nervous system. PMID- 1497096 TI - The crumbling service infrastructure: the decline of the nonprofit agency. PMID- 1497097 TI - Privatization of mental health services: the invisible hand at our throats. PMID- 1497095 TI - Calcification of allograft aortic wall in a rat subdermal model. Pathophysiology and inhibition by Al3+ and aminodiphosphonate preincubations. AB - Aortic allograft conduits and valves frequently undergo calcific degeneration. To study this problem, a rat subdermal model of nonvalved aortic wall allograft calcification was characterized, and experimental studies were carried out to test the hypothesis that aortic allograft preincubation in either amino propanehydroxydiphosphonate (APDP) or AlCl3 would inhibit calcification in a rat subdermal model. Fresh thoracic aortas were harvested under sterile conditions from male Sprague-Dawley rats (350-400 g). APDP aortas were preincubated immediately in either 4 x 10(-3) mol/l, 4 x 10(-4) mol/l, or 4 x 10(-5) mol/l [14C] APDP (37 degrees C, pH 7.4) and controls were incubated in 0.05 mol/l HEPES buffer (pH 7.4, 37 degrees C, 30 min). Al3+ aortas were preincubated in either 10(-1) mol/l, 10(-2) mol/l, or 10(-3) mol/l AlCl3. Pretreated aortas were next implanted subdermally in weanling rats (3-week-old, male, Sprague-Dawley, 50-60 g) and retrieved after 21 days. Control explants retrieved at intervals up to 21 days demonstrated progressive calcification with bulk aortic allograft Ca2+ levels increasing from a preimplant value of 0.8 +/- 0.1 micrograms/mg to 129.8 +/- 12.9 micrograms/mg by 21 days. Light microscopy revealed that much of the calcium deposition was associated with elastin. Calcification was significantly inhibited in the 4 x 10(-3) mol/l and 4 x 10(-4) mol/l APDP preincubated groups was observed (Ca2+ = 0.70 +/- 0.15 micrograms/mg, 36.6 +/- 19.8 micrograms/mg, respectively versus 117.2 +/- 24.3 micrograms/mg, control). Inhibition of calcification in the groups preincubated in the two most concentrated AlCl3 solutions (Ca2+ = 13.9 +/- 4.9 micrograms/mg [10(-2) mol/l AlCl3], 36.6 +/- 7.1 micrograms/mg [10(-3) mol/l AlCl3], 171.0 +/- 13.2 micrograms/mg [control]) was also demonstrated. No adverse effects of either pretreatment, APDP, or AlCl3 were noted on bone or overall somatic growth. PMID- 1497098 TI - Out of mind--out of sight. PMID- 1497099 TI - Reaching vulnerable populations: a framework for primary service role expansion. AB - An ecological framework is presented for assessing the feasibility of expanding the roles of primary service providers. Role conflict, interprofessional tensions, role anomalies, training and supervision, practitioners' tacit knowledge, and service user acceptance are among the factors assessed. The use of this conceptual framework for reaching a broader client population is discussed, together with its implications for professional practice. PMID- 1497100 TI - Children of survivors of the Nazi Holocaust: a critical review of the literature. AB - This review of published research on children of Holocaust survivors focuses on new directions taken in clinical and experimental studies during the past decade. Methodological problems persisting from earlier research are considered, and suggestions for future research strategies are offered. PMID- 1497101 TI - The cultural consultant in mental health care: the case of an Arab adolescent. AB - Limited understanding by mental health providers of an immigrant's cultural background can lead to misdiagnosis and inappropriate treatment. A case involving the psychiatric hospitalization of an adolescent from Iraq is described, as are the role of a cultural consultant in clarifying cultural issues and the positive consequences for diagnosis and treatment. Implications for the training and function of cultural consultants in mental health care are discussed. PMID- 1497102 TI - Psychological responses of rescue workers: fire fighters and trauma. AB - The psychological responses of two groups of fire fighters were examined following the performance of rescue work. Four types of responses were reported: identification with the victims, feelings of helplessness and guilt, fear of the unknown, and physiological reactions. Stress was found to be mediated by availability of social support, type of leadership, level of training, and use of rituals. Implications of these findings for preventive intervention measures are discussed. PMID- 1497103 TI - Traumatized children and the news media: clinical considerations. AB - Child victims of catastrophic incidents are often deluged by the news media and by the consequences of instant celebrity status but little is known about the effects of such publicity on these children. Several possible negative consequences for the children are discussed, as are some potential benefits. Suggestions are made for measures to minimize potential trauma arising from media attention. PMID- 1497104 TI - Attention deficit hyperactivity disorder: an epidemiological screening method. AB - Multistage identification, an epidemiological screening method of diagnostic assessment, was used to identify attention-deficit hyperactivity disorder (ADHD) in 1,490 elementary-school students. Children diagnosed with ADHD exhibited more impairment on adjustment measures and were more likely to have coexisting disruptive behavior disorders than were children diagnosed as subclinical non ADHD. PMID- 1497106 TI - Maternal and environmental characteristics as predictors of child behavior problems and cognitive competence. AB - Maternal and environmental characteristics as predictors of behavioral problems and cognitive competence in 505 Israeli kindergarten children were investigated. Events in closer temporal proximity to assessments of functioning appeared more predictive than those in early infancy. Findings support the need to include variables reflecting maternal characteristics in any prediction of child outcome and to consider the sex of the child in selection of variables. PMID- 1497105 TI - The role of parent training in treatment of preschoolers with ADDH. AB - The efficacy of group parent training was assessed in improving compliance and time on task in preschoolers with attention-deficit disorder with hyperactivity. Positive effects were obtained on measures of child compliance, but not on measures of attention. Parental compliance-management skills and overall style of interaction were also positively affected. The use of parent training for early intervention with ADDH children is discussed. PMID- 1497107 TI - Parental divorce, adolescence, and transition to young adulthood: a follow-up study. AB - In a long-term study of the effects of divorce, children in a Finnish town who had completed questionnaires in school at age 16 were followed up with postal questionnaires at age 22. Depression in young adulthood was found to be slightly more common among children from divorced families. In addition, the life trajectories of children in divorced families revealed more stressful paths and more distress in both adolescence and young adulthood. PMID- 1497108 TI - Depressive affect in "normal" adolescents: relationship to life stress, family, and friends. AB - Self-reported depressive affect was examined in high school students in relation to stress and the quality of relationships with family and friends. Higher levels of depressive affect were connected with stress around sexuality and achievement, lower levels of family cohesion, and more problematic peer relationships. The effects of high stress were buffered for boys by positive peer relationships, and for girls by cohesive family relationships. PMID- 1497109 TI - Runaway and homeless youth: the effects of attachment history on stabilization. AB - The effects of attachment antecedents on response to stabilization were examined in a group of runaway and homeless youth aged 12 to 17 years. The attachment histories of those who were not responsive to stabilization showed significant differences on several measurable criteria from the attachment histories of those who were responsive. The clinical and programmatic relevance of these findings is discussed. PMID- 1497110 TI - Patterns of adolescent psychiatric hospitalization: implications for social policy. AB - Demographic and institutional patterns of psychiatric inpatient treatment of adolescents in California in 1987 were analyzed with a focus on the roles of funding sources, ethnicity, and age in access to care, type of institutionalization, and length of stay. Privately insured white youths were found to be overrepresented in private psychiatric hospitals, while minority youths were underrepresented in private hospitals and overrepresented in juvenile detention facilities. Implications for policy issues are discussed. PMID- 1497111 TI - Optimal length of stay in child and adolescent psychiatric hospitalization: a study of clinical opinion. AB - Factors contributing to clinical recommendations for length of hospitalization for children and adolescents were investigated. Diagnosis, chronicity, severity of symptoms, response to prior treatment, and family resources were found to relate strongly to length-of-stay recommendations. Guidelines representing the consensus of experienced clinicians are proposed. PMID- 1497112 TI - Adolescent suicide attempts: outcomes at follow-up. AB - Adolescents seen in a general hospital emergency department or psychiatrically hospitalized were followed up at one month and three months following a suicide attempt. Findings included substantial drop-out rates for psychotherapy and high rates of repeated suicide attempts by three months. Implications for disposition planning and care of such adolescents are discussed. PMID- 1497113 TI - Omissions in assessment of work roles: implications for evaluating social functioning and mental illness. AB - An analysis of data from a longitudinal study of individuals during and after psychiatric hospitalization found that multiple work roles often remain unconsidered in assessments of social functioning and psychiatric status. The inclusion of such multiple roles was found to be important for adequate measurement of productive functioning and to illuminate their interaction with individuals' psychopathology. PMID- 1497114 TI - Child sexual abuse histories among African-American college students: a preliminary study. AB - Data from questionnaires completed by 1,040 African-American college students were analyzed for prevalence of child sexual abuse among this population. Rates were found to be similar to those in other studies of both general populations and female college students. Results of the study are discussed and directions for further research suggested. PMID- 1497115 TI - Comparison of cell surface antigen HBA71 (p30/32MIC2), neuron-specific enolase, and vimentin in the immunohistochemical analysis of Ewing's sarcoma of bone. AB - The HBA71 antigen is an M(r) 30,000/32,000 cell surface glycoprotein (p30/32MIC2), encoded by the pseudoautosomal MIC2 gene on chromosomes X and Y, that is expressed in Ewing's sarcomas. Immunohistochemical studies demonstrate a striking specificity for HBA71 among neoplasms of diverse histologic types. In the present study, 43 cases of Ewing's sarcoma of bone were tested for HBA71 expression and six additional immunohistochemical markers regularly used in the differential diagnosis of small round-cell tumors of childhood and adolescence (neuron-specific enolase, vimentin, leukocyte common antigen, cytokeratins, muscle-specific actin, desmin). The study design included (a) random selection of Ewing's sarcoma cases from the files of Memorial Hospital beginning in 1968, (b) blind review of the original histopathologic diagnoses of ES, (c) side-by-side immunohistochemical study of recut histologic specimens, and (d) statistical analysis of immunohistochemical findings in view of clinical outcome. Of the seven antigens studied, only HBA71, neuron-specific enolase and vimentin were expressed in a significant proportion of cases. Forty-one of the 43 cases were HBA71+ (95% sensitivity); of these, 21 were neuron-specific enolase+, 29 were vimentin+, and 15 were both neuron-specific enolase+ and vimentin+. One tumor lacked all antigens, and one was vimentin+ only. Comparison of tumor tissues in five patients obtained before and after cytostatic chemotherapy showed no change in HBA71 expression or in the other antigens tested. Product-limit survival analysis (median disease-free survival was 27.3 months for the study cohort) revealed no significance of neuron-specific enolase or vimentin marker status. These results raise doubts about the usefulness of neuron-specific enolase and vimentin immunohistochemistry to distinguish Ewing's sarcoma from other small round-cell tumors of childhood and adolescence or as prognostic indicators in Ewing's sarcoma. The positive identification of Ewing's sarcoma of bone now becomes a reality using HBA71 immunohistochemistry, either as a sole method or in combination with chromosomal breakpoint analysis. This may result in achieving uniform diagnostic criteria for evaluating the biologic, therapeutic, and prognostic aspects of Ewing's sarcoma and related neoplasms. PMID- 1497116 TI - Perineurioma: an uncommon soft tissue neoplasm distinct from localized hypertrophic neuropathy and neurofibroma. AB - Perineurial cells, which normally surround the nerve fascicles within a nerve, can be distinguished from Schwann cells by their immunoreactivity for epithelial membrane antigen (EMA) and lack of reactivity for S-100 protein. We report two cases of perineurioma, a tumor composed exclusively of perineurial cells and distinct from other nerve sheath tumors. The first case involved a deep, soft tissue mass of the neck, and the second involved a tumor located in the infraclavicular subcutaneous tissue. Both tumors were well circumscribed. Histologically, they were hypocellular and composed of spindle cells possessing elongated nuclei and bipolar, wavy, slender, strikingly elongated cytoplasmic processes, disposed in a background of collagen in the form of short bundles and whorls. In the first case, there were frequent calcospherites and remnants of a small nerve at the periphery. The spindle cells stained for EMA but not S-100 protein, chromogranin, neuron-specific enolase or Leu-7. Ultrastructurally, they possessed long cytoplasmic processes with incomplete basal lamina and occasional pinocytotic vesicles. Axons were not identified. Review of the literature shows that genuine perineuriomas are rare, and most cases reported as such are merely examples of localized hypertrophic neuropathy, a mononeuropathy characterized by fusiform swelling of a nerve, usually in the extremities. The involved segment in localized hypertrophic neuropathy contains distended fascicles composed of whorls of perineurial cells and fibrous tissue entrapping residual axons, probably representing a hyperplastic reaction to nerve damage. The term perineurioma should be reserved for the neoplasm composed only of perineurial cells and presenting as a soft tissue tumor.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1497117 TI - Angiomatosis of soft tissue. An analysis of the histologic features and clinical outcome in 51 cases. AB - The clinicopathologic features and clinical behavior of 51 cases of angiomatosis of soft tissue are analyzed. We have defined this lesion as a histologically benign vascular lesion that affects a large segment of the body in a contiguous fashion either by vertically involving multiple tissue types (e.g., subcutis, muscle, bone) or by involving similar tissue types (e.g., multiple muscles). Such lesions usually present in the first two decades of life and have a highly characteristic but not totally specific histologic pattern. The common pattern consists of a haphazard proliferation of vessels of varying sizes, particularly large veins. The latter have irregularly attenuated walls and intimal redundancies. However, the most distinctive feature is the presence of clusters of capillary vessels residing within or just adjacent to the vein walls. A second but uncommon pattern is that of clusters of capillary-sized vessels infiltrating the soft tissues. Both types are typically associated with large amounts of fat, suggesting that these lesions are more generalized mesenchymal proliferations rather than exclusive vascular lesions. This idea is supported by one unique case that included as part of the lesion a diffuse proliferation of glomus cells. Follow-up information in 25 cases (median 5 years; range 1-24) indicated that 22 patients experienced local recurrences. Nine patients developed more than one recurrence. There was no correlation between the age of onset of the lesion and the number of recurrences.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1497118 TI - Prostatic tissue in mature cystic teratomas of the ovary. AB - We report two examples of mature cystic teratomas of the ovary containing prostatic tissue. Both were incidental findings in teratomas that were otherwise typical at clinical and pathologic levels. The prostatic tissue contained ducts and acini in a simple branching pattern similar to that seen in the peripheral zone of the prostate gland. Transitional cell elements were present in both cases and compact acini resembling Cowper's gland were noted in one. No testicular or Wolffian duct tissue was noted. The immunohistochemical staining pattern of the glands was identical to that seen in normal prostate. In a literature review, four additional cases were identified. The presence of prostatic tissue in a 46XX tumor suggests induction by locally produced androgen. Some investigators have identified luteinized stromal cells and indicated these as the source of this androgen. Other possible androgenic origins include ovarian hilar cells, adrenal cortex, and tumor cells. PMID- 1497119 TI - Epithelioid and spindle-cell hemangioendothelioma of the spleen. Report of a distinctive splenic vascular neoplasm of childhood. AB - A case of a distinctive vascular neoplasm of the spleen in a 3-year-old boy is described. The tumor was characterized histologically by a biphasic growth pattern, with discrete nodular areas composed of atypical round, epithelioid cells with large nuclei and prominent nucleoli, and areas showing an intricate proliferation of vascular channels lined by elongated spindle cells. Immunohistochemical studies showed cytoplasmic staining of the tumor cells with factor VIII-related antigen, Ulex europaeus lectin, and vimentin antibodies. Stains for keratin, actin, desmin, lysozyme, and S-100 protein were negative in the tumor cells. Electron microscopy revealed a fairly cohesive population of cells that contained mature and immature cell junctions, basal lamina material, and surface pinocytotic activity consistent with vascular endothelial cells. Five year follow-up has shown the patient to be alive and free of disease. This case appears to represent a previously unreported primary vascular neoplasm of the spleen showing combined features of epithelioid and spindle-cell hemangioendothelioma. The lesion should be distinguished from other benign and malignant vascular proliferations of the spleen such as Kaposi's sarcoma, angiosarcoma, and the recently described littoral-cell angioma. PMID- 1497120 TI - Elastofibromatous change of the rectum. A lesion mimicking amyloidosis. AB - We report the case of a 58-year-old woman who had a 7-year history of multiple myeloma and multiple rib fractures and who presented with dysphagia. She underwent thorough gastrointestinal evaluation to rule out the possibility of amyloidosis. Although upper gastrointestinal biopsies were negative, the rectal biopsy was characterized by extensive smudgy eosinophilic deposits in the submucosa that closely resembled amyloid, except that they were not congophilic. Fibers with serrated borders characteristic of those in elastofibroma were identified and confirmed by means of elastic stain and electron microscopy. Elastofibromatous change of the gastrointestinal tract is a rare lesion that has been reported once previously in association with gastric ulcer. This case illustrates that it may occur as a spontaneous or subclinical finding in the absence of other pathologic lesions. The close resemblance between elastofibromatous change and amyloid deposits necessitates the appropriate histochemical and ultrastructural studies. PMID- 1497121 TI - Primary carcinoid tumor of the cystic and common bile ducts. AB - We report a case of primary carcinoid tumor arising at the confluence of the cystic and common bile ducts. The patient was a 64-year-old woman who developed a sudden onset of biliary colic and jaundice. Computerized tomography and nuclear magnetic resonance showed a mass lesion close to the head of the pancreas. At laparotomy a nodular lesion was found at the confluence of the cystic and common bile ducts. Microscopic observation revealed a type B-C carcinoid (Soga's classification) with positive immunoreactivity to chromogranin and cytokeratin. The presence of neurosecretory intracytoplasmic granules was demonstrated by electron microscopy. Flow cytometry showed diploid DNA content of the neoplastic cells with less than 5% of the nuclei in the S-phase region. PMID- 1497123 TI - Proposals: modest and immodest. PMID- 1497122 TI - Proposals: modest and immodest. PMID- 1497124 TI - Proposals: modest and immodest. PMID- 1497125 TI - [Intraoperative awareness in balanced anesthesia. A literature review based on a randomized double blind study using fentanyl, pentazocine and ketamine]. AB - Since the first case report by Winter-bottom [106], the problem of intraoperative awareness or recall has received increasing attention from patients, anaesthesiologists and, more recently, even law courts [4, 20, 21, 78]. Our own interest in awareness derives from a study with the opiate agonist tramadol as a supplement to balanced anaesthesia, which revealed an unexpectedly high incidence of about 65% of patients who could recall intraoperative music [55]. It was the aim of the present randomized double-blind study to evaluate, under identical experimental conditions, what the incidence would be with other analgesic supplements to balanced anaesthesia (fentanyl, pentazocine and ketamine). Because few reports on this subject are available in the German literature, it was felt that the result should be discussed within a comprehensive review. PATIENTS AND METHODS. A total of 60 patients (ASA I-II, age 27-66 years, weight 48-93 kg) undergoing elective gynaecological surgery of at least 90 min duration were each randomly assigned to one of three study groups (F, fentanyl; P, pentazocine; K, ketamine). Premedication was performed with diazepam 10 mg p.o. the evening before surgery and pethidine 1 mg/kg i.m.+promethazine 1.5 mg/kg i.m.+atropine 0.5 mg i.m. 60 min before anaesthesia. Induction was performed with alcuronium (2 + 8 mg), methohexital (1.5 mg/kg) and a bolus dose of the analgesic supplement (F, 5 micrograms/kg; P or K, 2 mg/kg), followed by continuous infusion (F, 2 micrograms kg-1 h-1, P or K 0.8 mg kg-1 h-1). Endotracheal intubation was performed with succinylcholine (1 mg/kg). Patients were ventilated to normocarbia using a Takaoka respirator (4 breaths/min, tidal volume 1600 ml, N2O/O2 75:25). If insufficient anaesthesia was suggested by increases in blood pressure or heart rate to more than 20% of preinduction values, excessive sweating or lacrimation, enflurane (0.5-2 vol.%) was added for short periods of time. At the end of surgery, patients were ventilated with 100% O2, and the neuromuscular block antagonized using atropine 0.5 mg and neostigmine 1 mg. Without prior announcement, tape-recorded music (Mantovani, 3 min followed by 3 min silence) was played to all patients via earphones throughout the time period between intubation and the end of nitrous oxide administration. Vegetative parameters, cumulative and relative enflurane application times and retrospective judgement of quality of anaesthesia by the anaesthesiologist were documented. Post operative recovery and pain were monitored using verbal rating scales. Patients were interviewed immediately after extubation and on the day after surgery to determine the incidence of dreams and recollection of music. Patients were classified as amnestic if they could not recall the music, even with prompting, and partially amnestic if they remembered the music but were unable to define the time when they had heard it. No amnesia was assumed if patients recalled the intraoperative music spontaneously. Groups were statistically compared by means of analysis of variance, Mann-Wilcoxon rank sum test and chi-square test. RESULTS. Mean duration of anaesthesia was 129-134 min in the subgroups. The total analgesic supplement dose was F 614 +/- 129 micrograms, P 238 +/- 38 mg, and K 230 +/- 50 mg (mean +/- SD). Enflurane substitution was necessary in 45 patients, regardless of the type of analgesic supplement. Mean cumulative enflurane application time was 26-28% in the treatment groups, corresponding to about 20% of anaesthesia duration. The most important reasons for enflurane substitution were increases in blood pressure (mostly in groups F and P) or heart rate (K). Recovery was fastest with F, followed by P, and slowest with K. Retrospective judgement of the quality of anaesthesia by the anaesthesiologist did not differ significantly between the treatment groups. Most (93%) of the patients were satisfied with their anaesthesia; 2 patients each who received P and K were dis PMID- 1497126 TI - [Spontaneous liver rupture as a rare complication of the HELLP syndrome]. AB - The HELLP syndrome (haemolysis, elevated liver enzymes, low platelet count) was first referred to by Weinstein in 1982 as an extremely progressive form of gestosis. In addition to the more common gestotic symptoms, such as oedema, proteinuria and hypertension, the clinical picture is characterized by microangiopathic haemolysis, thrombocytopenia and, especially, impaired hepatic function. Within this clinical picture severe complications can occur, such as eclamptic attacks, renal dysfunction, intracranial haemorrhage, intrahepatic haemorrhage and coagulopathy. An imbalance in prostanoid metabolism has been implicated in the pathogenesis. A decrease in synthesis of the vasodilator and thrombocyte aggregation inhibitor prostacyclin leads to a preponderance of the vasoconstrictor thromboxane A2, which promotes thrombocyte aggregation. This results in local vascular spasms and endothelial lesions, which in the case of hypercoagulopathy are accompanied by the formation of fibrin deposits with resultant vascular constriction. Intravascular fibrin deposits indicate that the coagulation system has been compromised and can lead to consumption coagulopathy in approximately 10% of cases. In the majority of cases, however, one finds low grade disseminated intravascular coagulation (DIC), i.e. mild hypercoagulopathy with thrombocytopenia, a tendency to thrombocyte aggregation and fibrinogen deficiency in the presence of usually normal plasmatic coagulation. These vascular changes occur particularly in organs that have high blood flow, such as liver, kidneys and placenta. In the liver, sinusoidal obstruction causes vascular congestion, leading to an increase in intrahepatic pressure, dilatation of Glisson's capsule, development of subcapsular hepatic haematomas and hepatic rupture. Hepatic haematoma virtually always requires surgical treatment, and otherwise the patient has hardly any chance of survival. Nevertheless, mortality is around 35%.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1497127 TI - [The action of flumazenil in combination with fentanyl on spontaneous respiration]. AB - Whereas the efficacy of flumazenil (Fl) for improving vigilance in the presence of other benzodiazepine agonists (BZA) is undoubted, its effect on BZA- and/or opioid agonists (OA)-induced respiratory depression is the subject of controversies. Some authors describe an improvement of a midazolam (Mi)-induced increase in paCO2, whereas others cannot find any influence on diazepam-induced respiratory depression. In two studies in which Fl was used to antagonize Mi/Fentanyl (Fe) anaesthesia we found even worse oxygen saturation values than with placebo (Pl). All our previous studies indicate a slight intrinsic activity of Fl on respiration in the presence of opioids. We therefore investigated the influence of Fl and Pl on expiratory pCO2 and oxygen saturation (SAT). METHODS. A group of 15 male, healthy volunteers aged 20-30 years gave written informed consent to participate in this double blind study, which was approved by our Institutional Review Board. Each subject received 3 micrograms/kg body wt. Fe + 0.5 mg Fl and 1 week later 3 micrograms/kg body wt. Fe + 5 ml NaCl 0.9% (Pl) i.v., in random order. They were undisturbed and breathed spontaneously. The following parameters were measured: SAT, pCO2 and heart rate (HR) continuously, using a pulse oximeter (SAT, H) and CO2 infrared absorption monitor (Oscar, Messrs., Datex). The blood pressure was recorded before and after a 5-min preinjection period (baseline) and at the end of the procedure (25 min). The data were stored in a microcomputer (Multitalent, Messrs. ZAK) and transmitted to a PC after each trial. STATISTICS. The groups were compared with the Wilcoxon rank sum test. P less than 0.05 is significant. RESULTS. In trials 1 and 2 there was an increase of pCO2 and a drop in SAT. The changes in pCO2 and SAT were more pronounced after Fe+Fl in 12 subjects (80%), as against 1 subject with the opposite result. There were 2 subjects who showed no difference between trials 1 and 2. The combination of Fe and Fl caused significantly higher increases in pCO2 (P = 0.007) and more pronounced decreases in SAT (P = 0.04) than Fe and Pl. DISCUSSION. These results indicate a slight enhancement of Fe-induced respiratory depression by Fl. In a previous study it could be shown that Fl antagonized the respiratory depressive effect of Mi, but baseline paCO2 was not completely recovered. In previous studies respiratory function impaired by Mi+Fe was initially improved by Fl, but rebound effects on SAT were observed, which were more pronounced than those after Pl. Therefore, respiratory function must be closely monitored in Fl-antagonized patients after Mi/Fe anaesthesia. PMID- 1497128 TI - [The refusal to consent to blood transfusion. Legal and medical aspects using Jehovah's Witnesses as an example]. AB - The limited understanding of a patient, such as a Jehovah's Witness, who has consented to an operation but refuses a blood transfusion for personal or religious reasons, places the physician in a moral dilemma. According to Article 2 II of the German Constitution, the fact that the patient has withheld or expressly refused his consent, i.e., in writing, mandates that the legal right of physical integrity be upheld with final legal effect, even in the case of an emergency. If this right to self-determination is abused, the person giving treatment is guilty of bodily harm in the sense of section 223 of the German Penal Code. Intraoperative haemodilution, the cell-save procedure, and colloidal and crystalloid volume replacement represent alternative methods of blood transfusion for Jehovah's Witnesses. PMID- 1497129 TI - [The significance of the initial respiratory parameters in assessing the severity of ARDS in children]. AB - In adults, the course and outcome of the acquired respiratory distress syndrome (ARDS) are closely related to the initial respiratory situation. Respiratory indices are frequently used for prognostic purposes and hence for the institution of new techniques such as extracorporeal lung support. The validity of these indices to predict the outcome in pediatric ARDS patients has not been examined as yet. We studied respiratory indices in 69 pediatric ARDS patients. METHODS. Out of 69 pediatric ARDS patients with various underlying diseases (Table 1), we chose 21 with a paO2/FiO2 ratio less than 150 mm Hg at some point to test the prognostic significance of a respiratory severity index (RSI), i.e., mean airway pressure x alveolar-arterial pO2 difference (A-aDo2)/paO2, a respiratory index (RI), i.e., A-aDO2-paO2/paO2, and other respiratory parameters (Table 2). Postsurgical patients, patients with incurable diseases, clearly non-respiratory deaths, and those treated with extracorporeal membrane oxygenation were excluded. We looked for statistical differences between survivors and nonsurvivors and correlations between ventilator days, intensive care unit (ICU) days, and hospital days and these indices. RESULTS. We did not find a significant difference between all respiratory indices tested at admission to the ICU and 24 h later between survivors and nonsurvivors (Table 3). Nonsurvivors initially had significantly higher blood pressures and lower heart rates. Both RSI and RI were significantly correlated to days on the ventilator, days in the ICU, and days in the hospital (Table 4). Initial multiorgan failure was significantly more common in nonsurvivors. CONCLUSIONS. Initial lung dysfunction as indicated by respiratory indices does not predict the outcome in pediatric ARDS. The underlying disease, hemodynamic situation, and age have to be considered in relation to the degree of lung dysfunction to determine new therapeutic strategies such as extracorporeal support. PMID- 1497130 TI - [Neonatal resuscitation in the delivery room. What role does the anesthetist play?]. AB - Neonatal resuscitation in the delivery room of small obstetric units is problematic because of the lack of on-site personnel with adequate training and experience. In large university hospitals this task is usually fulfilled by neonatologists who are present 24 h/day. However, in medium-sized and small obstetric units neonatal resuscitation is performed by a variety of professionals: paediatricians, obstetricians, anaesthetists, midwives, nurses, and nurse anaesthetists. The degree of responsibility and involvement of the anaesthesia specialist in the resuscitation of the newborn in Switzerland is unknown, and therefore an investigation was conducted. METHOD. After a telephone inquiry at all the hospitals in Switzerland, a total of 175 obstetric units were identified. A questionnaire with items regarding organisation, responsibilities, and the extent of involvement of the anaesthesia department of the particular hospital was sent to each of the appropriate anaesthetists. RESULTS. Of the 175 questionnaires, 163 (93%) were returned; 14 could not be analysed (5 were sent to hospitals where there was in fact no obstetric unit and 9 were sent to anaesthetists who shared responsibilities for one unit). In 1988, 76,505 babies were born in Switzerland; two-thirds of these were delivered in hospitals with an annual birth rate of less than 600 births per year. Of the 149 questionnaires that were eligible for further analysis, 118 (79%) documented participation of the anaesthetic team in the resuscitation of the newborn. However, only 22% of these departments had an official contract with the hospital administration. Ninety-nine per cent of all responders agreed that every anaesthetist should have the knowledge--both theoretical and practical--to resuscitate a newborn infant. However, reservations were expressed on how to acquire and how to maintain this competence. The initial evaluation of the newborn was done by an anaesthetist in 3% (2250/76,505) of all deliveries in Switzerland in 1988; 1.2% (882/76,505) of these babies needed bag-and-mask ventilation and in 0.4% (308/76,505) endotracheal intubation was performed by the anaesthetist. Proceeding on the assumption that 5% of all newborns need some sort of resuscitation immediately after birth, it is estimated that in 1988 approximately one-third of resuscitations were performed by anaesthetists. It is therefore concluded that anaesthetists play an important role in the resuscitation of newborns in Switzerland. PMID- 1497131 TI - [Bronchoscopy for initial care following severe thoracic trauma--basically indicated?]. AB - The study objective was to determine the usefulness of routine early (within 24 h after admission) and late (on the 3rd posttraumatic day) flexible fiberoptic bronchoscopy in patients with severe chest trauma. METHODS: By history, physical examination, and radiologic findings, we identified 15 consecutive patients, all of whom were anaesthetized, orally intubated, and mechanically ventilated. There was no change in ventilation, including FIO2, for bronchoscopy. The patients had continuous cardiovascular monitoring and peripheral pulse oximetry. The bronchoscope was inserted through a tight-fitting side port at the endotracheal tube connector. Pulse rate, mean arterial pressure, and arterial blood gases were recorded before, 1 min after, and 10 min after bronchoscopy, as were intracranial pressure (ICP) in 7 patients with an ICP probe (early bronchoscopy only) and the duration of the examination. Statistical significance was tested by means of the Wilcoxon test for correlating samples. Significance was assumed at P less than 0.05 in a two-sided test. RESULTS: Early bronchoscopy revealed two bronchial avulsions, two aspirations, and ruled out one suspected aspiration. Late bronchoscopy showed plugging of at least 3 segmental bronchi by clots in 4 patients, none of whom was able to expectorate effectively. In general, changes in the observed vital parameters were minimal. There was a significant but clinically irrelevant increase in mean pulse rate before and 1 min after early bronchoscopy. DISCUSSION: We conclude that bronchoscopy should always be considered in patients with severe chest trauma, the decision being based on typical radiological findings as well as clinical signs and symptoms. Given the proper indication, bronchoscopy supplies valuable information at minimal risk to the patient. PMID- 1497132 TI - [Obstetrical peridural anesthesia with bupivacaine and buprenorphine. A randomized double-blind study in comparison with untreated controls]. AB - Epidural anaesthesia with local anaesthetics has become a standard method of pain relief during labour. In recent years, spinal opiates, alone and in combination with local anaesthetics, have also been tried with varying degrees of success. Buprenorphine, a potent lipophilic opiate with long duration of action, has been used in several trials for caesarean section [3, 4, 6], but not yet in spontaneous labour. The aim of the present investigation was to evaluate epidural anaesthesia with bupivacaine alone and with bupivacaine+buprenorphine in comparison with no anaesthetic treatment in control parturients. METHODS. A total of 80 healthy women during labour at full term (age 18-38 years, weight 54-107 kg) were studied to evaluate the influence of 0.3 mg buprenorphine (group BB) vs placebo (group B) added to an initial dose of 15 ml plain bupivacaine 0.33% for lumbar catheter epidural anaesthesia. Plain bupivacaine 0.25% (10 ml) without any opiate admixture was used for reinjections. The control group was made up of 48 untreated parturients. After every injection, blood pressure, heart rate and respiratory rate were measured repeatedly, as were time intervals between injections, extent of blockade, duration of labour, actual and retrospective visual analogue pain score, and side effects such as pruritus, shivering or nausea and emesis. Maternal capillary blood gases were analysed three times during labour, and Apgar scores and venous and arterial umbilical blood gas analyses were obtained immediately after delivery. RESULTS. Admixture of buprenorphine 0.3 mg significantly increased the time interval between the first and second epidural doses (B: 162 +/- 47 vs BB: 224 +/- 64 min; mean, SD; Table 2) and significantly reduced the incidence of shivering (Table 9). The incidence of instrumental delivery was comparable in all groups (bupivacaine 32.5%, bupivacaine+buprenorphine 27.5%, control 21%; n.s.). No clinically relevant differences were observed between the epidural patients in onset and duration of the block (Fig. 1), analgesic efficacy (Fig. 2), duration of spontaneous labour (BB: 8.6 +/- 3.1 h, B: 8.5 +/- 2.9 h; n.s.) and vital functions of mothers and newborns. Although some statistically significant differences between the three groups were found in some parameters of the blood gas analyses (Table 7), the clinical condition of the newborns was always acceptable; Apgar scores were not significantly different. DISCUSSION AND CONCLUSIONS. The addition of buprenorphine to bupivacaine resulted in some advantages to the mother (reduced incidence of shivering) and the anaesthetist (time lapse before first reinjection was necessary) without jeopardizing the situation of the baby. Compared with untreated control parturients, retrospective pain scores during epidural anaesthesia with bupivacaine (with or without buprenorphine) were significantly lower. No clinically relevant disadvantages of epidural anaesthesia were observed. More studies are required to evaluate whether buprenorphine admixture allows a dose reduction of bupivacaine and could then claim clearer advantages than were found in the present investigation. PMID- 1497133 TI - [Transient total motor aphasia. A complication of an axillary brachial plexus block]. AB - Hypo- and hypertension, arrhythmias, bradycardia extending to cardiac arrest with circulatory failure, pneumothorax, allergic reactions with or without anaphylactic shock, production of methaemoglobin, vomiting, vertigo, disorientation, acoustic and visual disorders, tinnitus, slurred speech, muscle contractions, unconsciousness, and epileptic seizures are well-known complications associated with local anaesthetics. We have observed an additional central nervous system complication: a case of transient, total motor aphasia (Broca aphasia) in a 50-year-old patient after axillary blockade of the brachial plexus. Possible causes such as type and dosage of local anaesthetic or a transient ischaemic attack in the area of the prerolandic artery are discussed and related to the literature. Ultimately, however, it is still not apparent why this complication could appear although there was no overdosage intravascular injection, or abnormality of the pulse or blood pressure, and why its manifestation was limited to a motor aphasia. PMID- 1497134 TI - [A myoclonic seizure during propofol-alfentanil anesthesia?]. AB - Total intravenous anaesthesia with propofol and alfentanil is an established alternative to inhalation anaesthesia for intracranial neurosurgical procedures. Its usefulness has been somewhat overshadowed by reports of seizure-like movements, both during anaesthesia and in the recovery period. These can be related to the use of either anaesthetic agent, but true epileptogenic properties still remain to be demonstrated in man. Opioid-induced rigidity is a well known phenomenon and must not be mistaken for an epileptic seizure. Myoclonic motor activity can be observed even under physiological conditions, e.g. sleep. Almost all anaesthetic agents have been found to produce "epileptic" EEG changes (spikes, polyspikes, spike-wave complexes), but in man these have never been correlated to motor reactions. Propofol's pro- or anticonvulsive action is unclear. While some groups found shortened convulsing times in patients undergoing electroconvulsive therapy with propofol instead of methohexitone, others have reported activation of epileptogenic foci in the EEGs of known epileptic patients. A synergistic effect of propofol and alfentanil in the generation of seizure-like movements cannot be excluded. Whether seizure-like movements indicate a true "epileptogenic potency" of the anaesthetic drugs or are related to other phenomena remains to be studied. Electro-encephalographic monitoring during anaesthesia as well as careful observation and documentation of motor reactions may contribute to elucidation of the problem. We report a case of seizure-like movements during propofol-alfentanil anaesthesia for an elective craniotomy. A 52-year-old patient presented with a history of headaches of increasing frequency. A CT brain scan demonstrated a tumor in the left occipital region.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1497135 TI - [Comments on the paper by O. Michel and T. Brusis. Hearing disorders following spinal anesthesia]. PMID- 1497136 TI - [The growth of pathogenic germs in propofol]. PMID- 1497137 TI - 1993 LabGuide. PMID- 1497138 TI - Tissue expansion in pig skin--a histochemical approach. AB - In the present study, a porcine model for controlled skin expansion was investigated to improve our understanding of epidermal and vascular responses following stretching. The model is of outstanding importance not only for the clinical use of tissue expansion but provides interesting data for skin physiology and oncology, too. Thirteen out of 15 animals, who underwent silicone tissue expander implantation showed good clinical results. In all of them, skin biopsies were taken at the end of a controlled tissue expansion procedure (final expander volumes 350 or 500 ccm): one tissue specimen was obtained from the centre of the expanded skin area and a second from the neighbouring but nonexpanded skin. The tissue specimens were immediately frozen in liquid nitrogen and processed to 4 microns thick acetone-fixed frozen sections. Lectin histochemistry and immunohistology were performed using the following techniques: direct and indirect immunofluorescence technique (DIFT, IIFT), immunoperoxidase technique (POX) with either 3,3'-diamino-benzidine (DAB) or 3-amino-9-ethyl carbazole (AEC). The histochemical findings were supplemented by measurements of the number of vital epidermal cell layers, the epidermal thickness (microns), and the papillary vascular count per visual field. There was a significant diminuation of the vascular count (mean +/- S.D. = 55.0% +/- 12.5%; U-test: p less than 5%). By immunohistochemistry, a loss of the basal cell reactivity for the following antibodies was noted: ACAM (against calmodulin), K 8.12 (against keratins 13 +/- 16) and A51-B/H4 (against keratins 8, 14, 18). There was a remarkable increase of filaggrin expression in the uppermost spinal cell layers in expanded skin, which was most pronounced in those specimens with the shortest interval to the last fluid injection into the expander. We gained no evidence for alterations of the expression of suprabasal epidermal keratins, lectin binding sites (UEA I, PNA, ConA, WGA), and vascular lectin- and immunoreactivity due to tissue expansion. The subdermal capsule, which had formed around the silicone expander, was strongly vimentin-reactive. In conclusion, controlled tissue expansion is capable to change the basal cell phenotype--a feature which is shared with a number of conditions with increased proliferative activity and with the epidermis covering different skin tumours. The regular expression of suprabasal keratins and epidermal lectin binding sites provides evidence for a normal epidermal cell differentiation. Furthermore, the porcine skin is a reliable model for studying physiology and pathophysiology of human skin. PMID- 1497139 TI - Studies on the parietal region of the cervid skull. I. Remarks on the os interparietale in the skull of the roe deer (Capreolus capreolus L.). AB - In the roe deer skull symmetrically arranged ossa interparietalia were found to develop from paired centers of ossification. Obliteration of the sutura interinterparietalis mostly started already late in prenatal life, whereas closure of the interparietal and the interparietoparietal sutures as a rule commenced around the second week post partum. A certain degree of variability with respect to the timing of sutural closure was observed. No synostosis occurred between the os parietale resp. os interparietale and the os supraoccipitale, so that even in old animals the sutura parieto- resp. interparietooccipitalis was always present. PMID- 1497140 TI - Sexual dimorphism of the kidney in the NMRI mouse as shown by Dolichos biflorus agglutinin labelling. AB - The histological affinity pattern of Dolichos biflorus agglutinin (DBA) in kidneys from mice (NMRI, Balb/c, CBA) and rats (Wistar) fixed by perfusion with formalin, Bouin, or HgCl2 was investigated with a horseradish peroxidase conjugate. The animals were examined from fetal stage to adulthood. Adult female NMRI mice exhibited constant DBA labelling, with DBA binding to cells of the proximal and collecting tubules. Moreover the vascular endothelium of the renal papilla was found to be DBA-positive in 50% of adult female animals. In contrast, there was only very little DBA binding in the kidneys of male adult NMRI mice. There was no sexual dimorphism in lectin labelling in kidneys from other strains of mice or from rats. PMID- 1497141 TI - [Thr arteries of the male sex organs of Japanese quail (Coturnix coturnix japonica) and their development after hatching]. AB - A total of 83 male Japanese quails of the following age groups were used for this study: 11, 18, 25, 32, 35, 37, 39, 41, 43 days, and 7, 9, 17 weeks after hatching. Neoprene-Latex, Tensol-Cement, and the china ink were injected via the aortic arch. In most of male Japanese quails, the testes are supplied by the A. testicularis originated from the Aorta descendens through a common trunk with the A. renalis cranialis. But in only 3 quails had this artery originated directly from the Aorta descendens on either side. In 9 quails had the A. testicularis accessoria originating independently from the Aorta descendens and running cranially or caudally in short distance to the normal A. testicularis. The arteries for the Ductus deferens were divided into 3 categories. The Rami ureterodeferentiales craniales were spread out from A. testicularis or Rami epididymales. The Rami ureterodeferentiales medii came from the A. renalis media and the A. renalis caudalis. The Rami ureterodeferentiales caudales originated from the A. caudae lateralis and A. pudenda. The Receptaculum ductus deferentis, the Corpus vasculare paracloacalis and the Phallus nonprotrudens in the Cloaca were supplied from the thick Ramus cloacalis of the A. pudenda. The Ramus bursalis of this artery supplied the Glandula proctodaealis and the Bursa cloacalis, and was also thick. The arteries to the genital organs were observed in the 11 day old male quail. The A. pudenda began developing at about 30 days after hatching when the quail's body matured. While the A. testicularis began developing at about 40 days after hatching when the male Japanese quail was full of the spermatogenic activity. PMID- 1497142 TI - Immunocytochemical study of the diffuse neuroendocrine system cells in equine lungs. AB - This study was undertaken to investigate the presence of neuroendocrine cells (N.E.C.) by immunocytochemical means in equine lungs during three distinct evolutionary periods: fetal, neonatal and adult. The authors identified bombesin, somatostatin and calcitonin secretory cells. In the fetal lungs the N.E.C. were located in the interstitial tissue and exhibited greater immunoreactivity to bombesin than to the other two neuropeptides studied. A large number of calcitonin-producing cells and a smaller number of bombesin-positive cells were seen in the bronchial and bronchiolar epithelium of newborn Equidae. In the adult equine lungs far fewer N.E.C. were observed than in the earlier stages. Somatostatin-producing cells were not seen in neonatal or adult lung tissue. PMID- 1497143 TI - Arrangement of the branches of the aorta abdominalis in the wood mouse (Apodemus sylvaticus). AB - Data on the distribution and variation of the abdominal arteries in the wood mouse, Apodemus sylvaticus, are given. Seventy specimens (44 males and 26 females) caught in the field were analyzed by injection of green latex solution and dissection. The general branching pattern of the aorta abdominalis is similar to those described in other rodents. There are certain differences, however, especially in the branching of the coeliac trunk, the origin of the genital arteries and the arrangement of the caudal mesenteric artery. Significant variability was detected in the distribution of the iliolumbar arteries about the testicular and ovaric arteries. Based on the observations and measurements carried out, some branching patterns of the aorta abdominalis are presented. PMID- 1497144 TI - Comparative structure and morphology of the goat sternum in West African dwarf and Danish Landrace breeds. AB - The structure and morphology of the sternum from 33 West African dwarf (WAD) and sixteen Danish Landrace breed goats were studied radiographically. In young kids of the Danish Landrace breed (DL), the number of sternal elements (Sternebrae) was six or seven with the fifth or the last but one being double in some animals due to bilateral bodies. All the sternal elements in the WAD breed appeared to have each a single locus of ossification and the number of sternal elements varied between 5, 6 or 7 at birth. In those goats with 5 or 6 sternal segments, bilateral indentations were observed on the left and right side on either the last or the last two segments. These indentations were considered to indicate a prenatal cranial coalescence of the last segments leading to the reduced number of sternebra. The structure and morphology of the sternum in neonatal kids for the two breeds appears to be basically different. 8 sternal and 5 asternal ribs were observed in animals of both breeds. The cartilaginous attachments of the ribs on the sternal segments were variable. A floating rib was also observed in one of the WAD goats. The comparative structure and morphology of other ruminant sternum is also discussed. PMID- 1497145 TI - Measurement of mechanical forces acting on the area pellucida of the early chick embryo. AB - We have designed a method for measuring mechanical forces acting on the area pellucida of the chick embryo between stages 1 to 5 of HAMBURGER and HAMILTON (1951). The coordinates of several points on the outline of the area pellucida were used as input, from which a computer program measured the changes in the position of similar points to produce a table of values which, we argue, reflect mechanical forces in the embryo. The results obtained are shown to be reproducible between embryos. The computer program and the measurements obtained were then used to predict the behaviour of surgical incisions made in the area pellucida, using the tables obtained from direct measurements of embryos and the coordinates of various points on the surface of the operated embryos. This procedure was applied to embryos cultured by the method of NEW (1955) and in-ovo. It was found that in those embryos cultured by EWS technique the computer predictions correspond very closely to shape measurements made directly from embryos. However, the correspondence is less close when applied to embryos in ovo. PMID- 1497146 TI - [Age-dependent development of the long hollow bones in white New Zealand meat rabbits and chinchilla-hybrid laboratory rabbits]. AB - The age dependent development of the long bones' diaphyses (humerus, os femoris and os tibiofibulare) was examined macroscopically, morphometrically and histologically using 15 White New Zealand Rabbits (WN) and 15 Chinchilla-Bastard Experimental-Rabbits (Chbb) in 5 different age groups. The main growth of bone occurs in the first three months of life. The remodelling from juvenile to adult bone began in the period from the 4th-12th week. The different bones show various characteristic remodelling zones for each localization. Until the 12th week the resorption of juvenile bundled bone predominates. Afterwards an increasing bone formation by osteal bone can be observed. The bone growth is terminated between the 17th and 33rd week. The os tibiofibulare in both breeds represents the major part of the compact bone area on the whole cross-section area. Principally the bone-remodelling process proceeds equally in both breeds. Breed dependent differences in the adult bone are seen in the construction of the circumferential lamellae. These are formed considerably more irregularly by the Chbb-rabbits than by the WN-rabbits. PMID- 1497147 TI - Hypertensive intracerebral hemorrhage stimulating acute myocardial infarction. AB - We describe the case of a patient who presented with cardiovascular collapse and ECG changes strongly suggestive of acute MI. Our experience and that of others with patients who had sustained intracerebral hemorrhage indicate the potential for this entity to be misdiagnosed as acute MI early in a patient's clinical course. Reports of mistaken administration of thrombolytic therapy to patients with pericarditis or aortic dissection, other conditions that may be electrocardiographically mimic MI, underscore the potential for error. Clinicians should consider the possibility of intracerebral hemorrhage before treatment of MI with thrombolytic agents. PMID- 1497148 TI - Didelphic uterus and unilaterally imperforate double vagina as an unusual presentation of right lower-quadrant abdominal pain. AB - Imperforate hymen should be considered in girls of menarcheal age with a history of amenorrhea and vague abdominal discomfort, particularly if associated with symptoms of urinary obstruction or constipation. Patients may present with severe dysmenorrhea and localized pain mimicking appendicitis if hematocolpometra is due to unilaterally imperforate hymen with duplicate vagina and didelphic uterus. Although this condition is exceedingly rare, the case presented stresses the importance of a careful history and physical examination of an adolescent girl presenting with symptoms of abdominal pain associated with menstruation. PMID- 1497149 TI - Diazepam use & intubation. PMID- 1497150 TI - Methohexital in the ED. PMID- 1497151 TI - Count to TENS. PMID- 1497152 TI - Use of comparison radiographs in the diagnosis of traumatic injuries of the elbow. AB - STUDY OBJECTIVE: To determine whether comparison radiographic views of the uninjured elbow result in increased diagnostic accuracy in elbow trauma. DESIGN: Physicians were provided with a short clinical summary and asked to interpret radiographs of the injured elbow or of both the injured and the uninjured elbow in a randomized fashion. SETTING: The radiology department in a university hospital. METHODS: Fifty sets of radiographs from 25 children with elbow injuries were reviewed by two residents, two emergency physicians, and one pediatric radiologist using a standard classification of injuries. For each child, there were two sets of radiographs: one of the injured elbow and one of both the injured and the uninjured elbow. Descriptive statistics were used to report the results. kappa statistics were used to determine interobserver and intraobserver agreement. Missed diagnoses were divided into those that were clinically relevant and those that were not. RESULTS: The overall percentage of correct diagnoses (one versus two elbow radiographs) were as follows: residents, 69% versus 70%; emergency physicians, 62% versus 67%; and pediatric radiologist, 74% versus 72% (P greater than .05). kappa scores for interobserver variability and intrarater agreement were in the moderate range (.383 to .805; kappa, .08). Clinically relevant diagnoses were missed by trainees and emergency physicians regardless of whether radiographs of just the injured elbow or both the injured and the uninjured elbow were interpreted. Incorrect radiograph interpretations were due to false-positives in 17 of 23 cases. CONCLUSION: Comparison radiographs of the uninjured elbow did not improve diagnostic accuracy in elbow trauma in the pediatric emergency department. PMID- 1497153 TI - Length-based endotracheal tube and emergency equipment in pediatrics. AB - HYPOTHESIS: Pediatric endotracheal (ET) tubes can be accurately selected based on body length using a specialized emergency tape. POPULATION: Derivation set: Two hundred five children undergoing elective surgery. Validation set: Two hundred thirteen children undergoing elective surgery. Each child served as his or her own control. METHODS: Derivation phase: Two hundred twenty-one children undergoing ET intubation for elective surgery had their body length and leak pressures measured. The 205 children who had leak pressures between 10 and 40 cm H2O constituted the derivation set. The body length for a given ET tube size was derived from the interquartile range of patient lengths in this derivation set. Sizes for other resuscitative equipment items were chosen by a panel of experts using a modified Delphi technique. This information was placed by length on a color-coded tape. Validation phase: The tape was validated by using it to select ET tube size in another group of 203 children undergoing elective surgery. Criteria for acceptable fit in this group included leak pressure as above and the anesthesiologists' decision to accept the tube size or to retintubate. In the validation phase, length-based ET tube selections were compared with age-based rules: (age + 16)/4, and (age + 18)/4. RESULTS: The tape selected the appropriate ET tube size by leak pressure criterion in 77% of the cases and was within +/- 0.5 mm of the "correct" size 99% of the time. This was significantly better (P less than .005) than two widely used age-based rules, which gave the correct initial size in only 47% and 9% of these cases, and were within +/- 0.5 mm for 86% and 59%. The anesthesiologists chose to continue with the tape-sized tube rather than to reintubate in 89% of cases. CONCLUSION: A system for length-based selection of emergency equipment represents a significant adjunct to emergency physicians and paramedics who must deal with critically ill children. Length based ET tube selection is clearly superior to age-based rules, which are difficult to remember and require accurate estimation of a patient's age. PMID- 1497154 TI - Transcutaneous cardiac pacing in the treatment of out-of-hospital pediatric cardiac arrests. AB - STUDY OBJECTIVE: To evaluate the effectiveness of transcutaneous cardiac pacing in out-of-hospital treatment of cardiac arrests in pediatric patients. DESIGN: We describe the outcome of patients treated during a prospective trial of transcutaneous cardiac pacing in the field. We compare their outcome with that of out-of-hospital arrests in submersion patients who were not paced. We identified patients from Seattle and King County Emergency Medical Services reports, hospitals, and medical examiner's registries. MEASUREMENTS AND MAIN RESULTS: Nine patients in cardiac arrest caused by drowning (six) and sudden infant death syndrome (three) were paced in the field. All were less than 6 years old. The one survivor was severely neurologically impaired and died six months later. Transcutaneous cardiac pacing produced electrical capture in two patients but no detectable pulse or blood pressure. Ten submersion patients less than 6 years old in cardiac arrest were not paced. One survived, with mild neurologic impairment at hospital discharge. CONCLUSION: Transcutaneous cardiac pacing was not effective and was not associated with improved survival. PMID- 1497155 TI - Clinical predictors of bacterial versus aseptic meningitis in childhood. AB - STUDY OBJECTIVE: To assess the reliability of meningeal signs and other physical findings in predicting bacterial and aseptic meningitis at various ages. DESIGN: Children requiring lumbar puncture were evaluated prospectively for meningeal signs and other physical parameters before lumbar puncture. SETTING: Emergency department of Children's Hospital of Wisconsin. PARTICIPANTS: One hundred seventy two children, aged 1 week to 17 years, with meningitis (53 bacterial and 119 aseptic). MEASUREMENTS AND MAIN RESULTS: Nuchal rigidity was present in 27% of infants aged 0 to 6 months with bacterial meningitis versus 95% of patients 19 months or older (P = .0001). Three percent of infants 0 to 6 months old with aseptic meningitis had nuchal rigidity versus 79% of patients 19 months or older (P = .0005). Seventy-two percent of infants 12 months of age or younger with bacterial meningitis has at least one positive meningeal sign versus 17% of infants with aseptic meningitis (P = .0001). Eighty-five percent of children older than 12 months with meningitis had at least one positive meningeal sign, 93% with bacterial meningitis, and 82% with aseptic meningitis. CONCLUSION: Despite a lack of meningeal signs, a high index of suspicion for meningitis is essential when evaluating the febrile infant 12 months of age or younger. PMID- 1497156 TI - Diagnostic value of anemia, red blood cell morphology, and reticulocyte count for sickle cell disease. AB - STUDY OBJECTIVE: To determine the diagnostic value of anemia, RBC morphology, and reticulocyte count for differentiating patients with sickle cell trait from those with sickle cell disease, who have acute medical or surgical conditions and a positive sickle cell screen. DESIGN: Retrospective chart review. SETTING: A midwest urban children's hospital with 220 beds and 36,000 emergency department visits per year. PARTICIPANTS: One hundred six patients with sickle cell trait and 152 patients with sickle cell hemoglobinopathies. RESULTS: Anemia was observed significantly more often in patients with sickle cell disease compared with sickle cell trait (P less than .001) at all ages 3 months and older. However, anemia alone as a diagnostic test lacked high sensitivity and specificity in children less than 4 years old. Sensitivity approached 100% with the presence of anemia, abnormal RBC morphology, or reticulocyte count of more than 2%. CONCLUSION: Absence of anemia alone does not exclude the diagnosis of sickle cell disease in children less than 4 years old. To differentiate trait from sickle cell disease, we recommend determination of not only hemoglobin adjusted for age but also of RBC morphology and reticulocyte count on all children presenting with acute medical and surgical conditions and a positive sickle cell screen. PMID- 1497157 TI - A randomized, double-blind, comparative study of the efficacy of ketorolac tromethamine versus meperidine in the treatment of severe migraine. AB - STUDY OBJECTIVE: To evaluate the relative efficacy of ketorolac tromethamine and meperidine hydrochloride in the emergency department treatment of severe migraine. DESIGN: Prospective, randomized, double-blind trial. SETTING: University hospital ED. PARTICIPANTS: Patients presenting to the ED with an isolated diagnosis of common or classic migraine. INTERVENTIONS: Subjects were randomized to receive a single intramuscular injection of either 30 mg ketorolac or 75 mg meperidine. MEASUREMENTS AND MAIN RESULTS: Of the 31 patients completing the trial, 15 received ketorolac and 16 received meperidine. The demographic characteristics of both groups were comparable. At one hour, ketorolac was significantly less effective than meperidine in reducing headache pain (P = .02) and in improving clinical disability (P = .01). Ketorolac also was less effective at reducing nausea, photophobia, and the need for rescue medication (P less than .05). Sustained headache relief was experienced by 44% of the patients treated with meperidine at 12- to 24-hour follow-up, compared with 13% of the patients treated with ketorolac (P = NS). No significant side effects were observed for either group. CONCLUSION: IM ketorolac tromethamine is less effective than meperidine in the ED treatment of severe migraine. PMID- 1497158 TI - Ketorolac for sickle cell vaso-occlusive crisis pain in the emergency department: lack of a narcotic-sparing effect. AB - STUDY OBJECTIVE: To determine if a single dose of intramuscular ketorolac given on presentation to the emergency department has a narcotic-sparing effect in adult patients with sickle cell vaso-occlusive crisis pain. DESIGN: A prospective, randomized, single-dose, double-blind study. SETTING: ED of a university hospital and an affiliated county hospital. TYPE OF PARTICIPANTS: Eighteen adult patients who presented to the ED with sickle cell crisis pain a total of 24 times. INTERVENTIONS: Patients were randomized to receive either ketorolac 60 mg IM or placebo on presentation to the ED. Subjects were administered meperidine on presentation and then received a standardized dose of meperidine every 30 minutes during the four-hour observation period based on the severity of pain. MEASUREMENTS AND MAIN RESULTS: The 12 subjects in the ketorolac group received an average of 231 +/- 92 mg meperidine, whereas the 12 subjects in the placebo group received an average meperidine dose of 250 +/- 85 mg (P = .61). CONCLUSION: The use of intramuscular ketorolac did not lead to a clinically significant reduction in the requirement for narcotics during the four-hour ED treatment period. PMID- 1497159 TI - Rapid-sequence intubation of head trauma patients: prevention of fasciculations with pancuronium versus minidose succinylcholine. AB - INTRODUCTION: Fasciculations during rapid-sequence intubation may lead to increased intracranial pressure and emesis with aspiration. Standard rapid sequence intubation requires a nondepolarizing blocking agent before succinylcholine administration. HYPOTHESIS: Prevention of fasciculations during rapid-sequence intubation of head trauma patients can be accomplished as safely and effectively with minidose succinylcholine as with a defasciculating dose of pancuronium. DESIGN: A prospective, randomized, double-blind study. SETTING: An inner-city county trauma center with 70,000 patient visits per year. PARTICIPANTS: Sequential adult head trauma patients requiring rapid-sequence intubation who had no contraindications to succinylcholine or pancuronium. INTERVENTIONS: Each head trauma patient requiring rapid-sequence intubation who met the inclusion criteria received standard rapid-sequence intubation maneuvers and lidocaine (1 mg/kg) IV. Patients were randomized to receive either minidose succinylcholine (0.1 mg/kg) or pancuronium (0.03 mg/kg) IV one minute prior to the full paralytic dose of succinylcholine (1.5 mg/kg) IV. Fasciculations were recorded using a graded visual scale. RESULTS: Of 46 patients, eight of 19 (42%) in the pancuronium group and six of 27 (22%) in the succinylcholine group experienced fasciculations. No statistically significant difference in fasciculations was detected between the two groups using chi 2 analysis. Complete relaxation of the cords was present in all but two patients, one in each group. No patient in either group experienced emesis or significant dysrhythmias. CONCLUSION: Pretreatment with minidose succinylcholine causes no greater incidence of fasciculations than pancuronium in rapid-sequence intubation of head trauma patients in an ED setting. Thus succinylcholine may be used as the sole paralytic agent in rapid-sequence intubation of head trauma patients. PMID- 1497160 TI - Cervical cancer screening in an urban emergency department. AB - STUDY OBJECTIVES: To determine the feasibility of Pap screening and follow-up of urban emergency department patients and the prevalence of cervical dysplasia and carcinoma in this group. DESIGN: During a four-month period, Pap smears were added to pelvic examinations performed in the ED. Follow-up, including repeat Pap smear or biopsy, was attempted on all abnormal smears. SETTING: Urban county hospital-based ED. INTERVENTIONS: Pap screening and follow-up. RESULTS: Dysplasia was present in 8% of screening Pap smears. Eighty-two percent of patients with dysplasia on screening Pap smear returned for follow-up. Four percent of screened patients received a confirmed diagnosis of CIN 1 or more following repeat Pap smear or biopsy. Two invasive cervical cancers were identified. CONCLUSIONS: There is a high prevalence of cervical dysplasia among women screened with Pap smears in an urban ED. Routine Pap screening in urban EDs can be an important component of cervical cancer control programs for high-risk women. PMID- 1497162 TI - Academic emergency medicine: a national profile with and without emergency medicine residency programs. AB - STUDY OBJECTIVE: Formal data are lacking regarding emergency departments in academic medical centers, particularly those without an emergency medicine residency program. The Education Committee of the Society for Academic Emergency Medicine conducted a survey to define a national profile of academic emergency medicine. DESIGN: Prospective survey with telephone follow-up. SETTING: Academic medical centers. PARTICIPANTS: One hundred twenty-three academic medical centers as defined by the Association of American Medical Colleges. RESULTS: Results were obtained from 94 (78%) institutions: 27 (29%) had an emergency medicine residency program and 67 (71%) had no emergency medicine residency program. Significant differences were found between those with and without emergency medicine residency programs regarding 24-hour attending coverage (96% versus 73%), mean weekly clinical faculty hours (26 versus 33), the number of emergency medicine board-certified faculty, faculty recruitment difficulties (25% versus 75%), and the presence of a curriculum for housestaff (96% versus 38%). No significant differences were noted regarding the presence of a curriculum for medical students (78% versus 64%). Of the 67 institutions with no emergency medicine residency programs, 42% were actively planning a program, and 42% would consider future development of a program. CONCLUSION: This article provides the first comprehensive profile of emergency medicine in the Association of American Medical Colleges academic medical centers. Programs with emergency medicine residency programs provided more 24-hour attending coverage, had more emergency medicine board-certified faculty, and reported less difficulty recruiting additional faculty than institutions with no emergency medicine residency program. Both need to expand their undergraduate educational activities. Many institutions with no emergency medicine residency program are attempting to develop emergency medicine residency programs. PMID- 1497161 TI - A comparison of observed and self-reported compliance with universal precautions among emergency department personnel at a Minnesota public teaching hospital: implications for assessing infection control programs. AB - STUDY OBJECTIVES: To determine the level of universal precautions compliance in a hospital emergency department by two methods (direct observation of subjects versus self-reporting by questionnaire). SETTING: A Level II trauma center located within a university-affiliated medical center in Minneapolis/St Paul, Minnesota. Glove and needle disposal containers were available in each treatment room; gowns, masks, and goggles were readily available. PARTICIPANTS: ED physicians (12 staff plus rotating residents), medical students, nursing staff, and ancillary personnel. METHODS: Ten observers documented six specific behaviors among ED personnel: needle recap frequency, needle recap techniques, and use of gowns, gloves, masks, and goggles. After the observations, surveys were distributed to ED personnel by intrahospital mail in Fall 1989. RESULTS: During 270 observation hours, 1,018 patient-worker interactions were recorded. Gloves were the barrier worn most frequently when appropriate (74%), followed by goggles (13%), gowns (12%), and masks (1%). Needles were recapped 51% of the time, and most needles that were recapped (79%) were recapped by the two-hand technique; 5% of all needles used were left uncapped at bedside or in the trash. Physicians were observed to use gloves more frequently than registered nurses and nursing assistants; nurses were observed to recap more frequently than physicians. From the survey, the three most common reasons for noncompliance involved time (71%), dexterity (61%), and patient appearance (50%). CONCLUSION: Universal precautions are not consistently used by ED personnel, and ED personnel significantly overestimate their compliance with universal precautions. PMID- 1497163 TI - Academic emergency medicine in United States medical schools. AB - OBJECTIVE: To determine the current standing of academic units of emergency medicine in allopathic medical schools and to measure the attitudes of medical school deans toward the specialty. DESIGN: An investigator-blinded survey of the senior deans of 123 allopathic medical schools in the United States. RESULTS: Ninety-four of 123 (76%) survey instruments were completed. Fifty-six medical schools reported having academic units of emergency medicine (five divisions of the dean's office, 16 full departments, 35 divisions/sections of other departments). Twenty-five of 56 units were reported to be academically less productive when compared with other specialty academic units of similar size. When overall mission (academic plus clinical/administrative) was considered, 46 of 56 units were reported as adequately fulfilling or exceeding mission expectations. Thirty-eight schools reported not having an academic unit of emergency medicine. Only ten of the 38 reported have no institutional support or plans for academic emergency medicine. CONCLUSION: Medical school deans are generally satisfied with the clinical/administrative performance of academic emergency medicine units but are less so with academic productivity. Despite the small numbers of full departments and disparate status of established units, it is noteworthy that only ten of the 94 respondents to this survey reported no support whatsoever for academic emergency medicine. PMID- 1497165 TI - Observation medicine curriculum. Observation Medicine Committee, Society for Academic Emergency Medicine. PMID- 1497164 TI - Cost of care in the emergency department: impact of an emergency medicine residency program. AB - STUDY OBJECTIVE: To evaluate the impact of an emergency medicine residency training program on the cost of care in the emergency department. DESIGN: A retrospective chart review was conducted of all ED encounters for a three-month period, six months before and six months after the introduction of an emergency medicine residency program into an urban community hospital. Physician staffing of this ED before the residency period was by nonemergency medicine residency trained emergency physicians. SETTING: A 27,000-visit-per-year urban community hospital ED. TYPE OF PATIENTS: A consecutive sample of all patients discharged home from the emergency center with one of six diagnoses. The diagnoses studied were viral upper respiratory infection, pharyngitis, acute asthma, seizure, lumbosacral strain, and cervical strain. MAIN OUTCOME MEASURES: Frequency of laboratory test and radiograph ordering pertinent to the evaluation of each diagnostic category were used as a marker of cost of care. RESULTS: The presence of the residency training program did not increase the cost of care as measured by test use and, for three of the six diagnoses, actually lowered the cost of care. This effect was most prominent in the evaluation of lumbosacral and cervical strain when the residency physicians ordered radiographs at a rate five and 2.3 times lower, respectively, than the previous group and in the approach to pharyngitis when they ordered throat cultures 2.8 times less frequently. CONCLUSION: As measured by selected test use for six common discharge diagnoses, the introduction of an emergency medicine residency program did not increase the cost of care in this urban community hospital ED. PMID- 1497166 TI - Emergency department observation beds improve patient care: Society for Academic Emergency Medicine debate. PMID- 1497167 TI - Outpatient wound preparation and care: a national survey. AB - STUDY OBJECTIVE: To sample the practice styles of emergency physicians caring for acute traumatic wounds. DESIGN: Written survey. SETTING: US emergency departments obtained from the American College of Emergency Physicians mailing list. SUBJECTS: Randomly selected ACEP members. MAIN RESULTS: One hundred fifty-one of 285 (53%) survey mailings were returned. Eighty-six percent of respondents were primarily clinicians, and the majority (61.6%) worked in EDs with annual patient visits between 21,000 and 50,000. The majority of respondents (64.2%) were certified by the American Board of Emergency Medicine. Nineteen percent managed wounds based on provider preference despite the existence of written wound management protocols. We identified a variety of practices that are contrary to current literature and textbook recommendations. Fifty-eight (38%) soaked wounds, whereas 21% used either 10% povidone iodine or hydrogen peroxide to cleanse wounds. One hundred one (67%) scrubbed the entire wound surface using, among other methods, cotton gauze (59%) or a coarse, bristle-laden sponge (38%). Forty (27%) irrigated wounds using techniques that have not been proven to deliver the 5 to 8 psi necessary for adequate tissue cleansing. Delayed primary closure, a treatment option for lacerations at increased risk for infection, was infrequently or never practiced by 76% of respondents. All respondents administered IV antimicrobials at least occasionally for simple outpatient lacerations. CONCLUSION: Methods of preparing, treating, and following outpatient wounds vary among emergency physicians, and these results support the idea that no de facto standard of care exists for this clinical problem. Outpatient wound care techniques routinely practiced (ie, soaking, scrubbing, use of full-strength hydrogen peroxide or full-strength povidone iodine) may be harmful based on limited animal and human research, whereas other proven techniques (ie, delayed primary closure) are infrequently practiced by many emergency physicians. PMID- 1497168 TI - Pap smears in a public hospital emergency department: a failure of the system. PMID- 1497169 TI - Academic emergency medicine. PMID- 1497170 TI - Ketorolac in the treatment of acute pain: the pendulum swings. PMID- 1497171 TI - Use of tetracaine, epinephrine, and cocaine as a topical anesthetic in the emergency department. AB - The combination of tetracaine, epinephrine, and cocaine has gained wide acceptance as a topical anesthetic agent for use on pediatric dermal lacerations in the ED. This is despite the fact that the optimal dose and formulation have yet to be determined. TAC can be applied painlessly to wounds and is about as effective as lidocaine infiltration for anesthetizing pediatric facial and scalp lacerations. It is relatively ineffective on lacerations located elsewhere or in adults. The most commonly used TAC solution contains high concentrations of cocaine, tetracaine, and epinephrine, drugs that individually can cause serious toxicity if absorbed in sufficient amounts. In addition, the three components of TAC may interact to potentiate their intrinsic toxicities. The deliberate and inadvertent application of TAC to mucous membranes has caused status epilepticus and two pediatric deaths. The risk of toxicity from misapplication of TAC is heightened because TAC is most effective and therefore most widely used on pediatric facial and scalp lacerations. Cocaine is also absorbed after TAC is applied to dermal lacerations and may cause toxicity by this route. Until additional research is performed to establish the minimum effective dose of TAC and its potential toxicity and until FDA approval is granted, we do not think that it can be recommended as the drug of choice for pediatric facial and scalp lacerations in the ED. If TAC is administered, a maximum dose of 2 to 3 mL of the "half-strength" formula proposed by Bonadio and Wagner should be used, and application should be performed by medical personnel, using a soaked gauze or cotton ball. Care should be taken to make sure none of the solution comes in contact with mucous membranes, and TAC should not be applied to lacerations involving the vermillion border of the lip or the lip itself. Close medical monitoring of the patient is essential to detect signs of toxicity. Research on other topical agents such as tetracaine with epinephrine is also needed. Although anesthetizing wounds painlessly remains a worthy goal, exposing patients to added and unknown risks and increasing the cost of health care is unacceptable. PMID- 1497172 TI - Encainide overdose in an infant. AB - Ingestion of as little as a single tablet of encainide resulted in life threatening ventricular arrhythmias in a child. Insertion of an intraosseous line permitted prompt delivery of medications and fluids. Prehospital care providers must be aware that apparently trivial amounts of some adult dosage forms can be toxic to small children. PMID- 1497173 TI - Percutaneous ultrasound-guided cholecystocentesis in cows. AB - A method was developed for percutaneous ultrasound-guided cholecystocentesis in cattle. The procedure was performed on the right side in the 9th, 10th, or 11th intercostal space of 30 cows. Of the 30 cows, 20 were slaughtered 24 hours after cholecystocentesis and the remaining 10 cows were slaughtered after a 10-day observation period. Changes in the peritoneum and gallbladder wall, observed at slaughter, were minimal. During the 10-day observation period, general behavior, attitude, and appetite of the 10 cows were normal. A transient, slight increase in rectal temperature was observed in 6 cows at 4, 5, or 8 days after cholecystocentesis. Total and differential WBC counts and total protein and fibrinogen concentrations, determined daily, were all within normal ranges. Bile samples from 20 cows were examined microscopically and biochemically. Fasciola hepatica and Dicrocoelium dendriticum eggs were observed in bile from 7 and 12 cows, respectively. Fecal examination revealed F hepatica eggs in 4 cows; D dendriticum eggs were not identified in any of the fecal samples. In 1 cow, F hepatica eggs were observed in the feces, but not in the bile. Bile acids concentration in bile varied from 12.5 to 68.5 mmol/L (mean +/- SD, 45.3 +/- 3.05 mmol/L) and in serum from 3.8 to 281.0 mumol/L (41.6 +/- 17.24 mumol/L). Negative correlation was obtained between bile acids concentration in bile and that in serum (r = -0.60, P less than 0.01). It was concluded that percutaneous ultrasound-guided cholecystocentesis in cows is a safe procedure and that microscopic and biochemical examinations of obtained bile can be useful diagnostic aids. PMID- 1497174 TI - Factors affecting skim milk progesterone assay results. AB - Five studies were performed to determine factors affecting progesterone concentration in skim milk. Results of the first study indicated that progesterone concentration was higher in skim milk of samples kept 16 hours in an ice bath (0 C) than of those left at room temperature (21 C). In the second study, this temperature effect was found to be reversible, with skim milk progesterone concentration increasing when whole milk samples were cooled prior to centrifugation. In the third study, [3H]-labeled progesterone was used to determine the relationship between fat content of foremilk (the first milk obtained from the teats), midmilk (milk obtained midway through milking), and strippings (milk obtained immediately after milking machines have been removed) samples and temperature (4 C and 21 C) on the percentage of progesterone in the skim milk fraction. The relationship between percentage of butterfat and percentage of progesterone in skim milk was linear when the log of these variables was used for calculations. In the fourth study, assayable progesterone in the skim milk fraction of foremilk, midmilk, and strippings was affected by temperature. In the fifth study, a multiple-regression procedure was used to determine the amount of variation in percentage of radioactive progesterone in the skim milk fraction. Independent variables (whole milk butterfat and temperature of incubation [1, 3, 13, 22, 37, and 50 C]) and the natural log of each variable, were entered into a stepwise multiple-regression analysis.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1497175 TI - Canine bone shape analysis by use of a radiographic image-classification system. AB - A radiographic image-classification system was developed to analyze and compare the shape of the humerus of neonatal Labrador Retriever and Labrador Retriever x Beagle pups that were either phenotypically normal or affected with an ocular skeletal dysplasia syndrome. The system consistently defined the shape of the humerus within the groups of pups studied and indicated a difference in the shape of the humerus between normal and affected pups. Results indicated that the radiographic image-classification system may be able to identify Labrador Retriever pups affected by the ocular-skeletal dysplasia syndrome at or shortly after birth. PMID- 1497176 TI - Effects of analog filtering on brain stem auditory-evoked potentials in dogs. AB - Effects of analog filter frequency on brain stem auditory-evoked potentials (BAEP) were investigated in 7 non-sedated dogs. The BAEP were recorded successively at various low-pass (LP) and high-pass (HP) filter frequency settings. The analog filters had a rolloff of 6 dB/octave. Decrease of LP filter frequency from 30 kHz to 100 Hz caused prolongation of the peak latency and reduction of the peak-to-peak (from a positive peak to the following trough) and absolute (from a positive peak to the baseline) amplitudes for all peaks, except the peak latency for P5 and the absolute amplitude for P4. Changes in these variables were statistically significant (P less than 0.05) at different cutoff frequencies specific for the individual peaks. The interpeak latency between P1 and P4, and P4/P1 peak-to-peak amplitude ratio were not changed significantly. At the lowest LP filter frequency of 100 Hz, positive peaks (fast waves) seemed to be superimposed on a slow positive wave (slow wave). In contrast, increase of HP filter frequency from 0.53 to 160 Hz did not result in significant changes for any peaks, except for reduction in the absolute amplitude of P4. The various effects of LP filter frequency and negligible effects of HP filter frequency on individual peaks may be attributable to their frequency composition and/or elimination of the slow wave at higher HP filter frequency settings. On the basis of our results, LP filter setting of 3 kHz and HP filter setting of less than or equal to 53 Hz are recommended for recording of BAEP in dogs.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1497177 TI - Quantitative renal scintigraphic determination of the glomerular filtration rate in cats with normal and abnormal kidney function, using 99mTc diethylenetriaminepentaacetic acid. AB - The nuclear imaging technique known as quantitative renal scintigraphy was validated as a means to assess the kidney function of cats. Renal function tests were performed in 6 healthy cats and 3 cats with clinical manifestations of kidney failure. In addition, the nephrotoxic drugs, gentamicin sulfate, or amphotericin B were used in an attempt to induce renal failure in 4 cats. Using linear regression analysis, equations were derived to estimate the glomerular filtration rate (GFR) on the basis of the renal percent uptake of 99mTc diethylenetriaminepentaacetic acid (99mTc-DTPA). One-way ANOVA and Student's t test were used to evaluate treatment effects on clearances of inulin and creatinine, percent uptake of 99mTc-DTPA, and serum creatinine concentrations. The results show that the percent uptake of 99mTc-DTPA by the kidneys correlated well with the GFR obtained through the clearance of inulin. Thus, it was concluded that quantitative renal scintigraphy, using 99mTc-DTPA as a marker of kidney function, is an adequate technique to estimate the kidney function of healthy cats and cats with functional renal impairment. The best estimate of the GFR of cats, using the percentage dose of 99mTc-DTPA, was obtained on the 1- to 3 minute postinjection interval of the marker, using data that was background subtracted, but not corrected for tissue absorption of gamma rays or binding of 99mTc-DTPA to plasma proteins. There was no significant difference in the mean inulin clearance, creatinine clearance, or percent uptake of 99mTc-DTPA between the 3 treatment groups of this study.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1497178 TI - Polypeptides associated with Pasteurella multocida infection in rabbits. AB - Polypeptides from whole cell preparations of Pasteurella multocida serotypes A:12 and A:3 were separated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and transferred to nitrocellulose paper. Antigens were detected by immunoblot analysis, using sera from 3 groups of rabbits. Sera were obtained from rabbits inoculated intranasally with P multocida serotype A:12 or A:3, from rabbits maintained in a rabbitry with enzootic P multocida A:12 infection, and from rabbits maintained in a rabbitry with enzootic P multocida A:3 infection. Immunoblot analyses of pre- and postinoculation sera from experimentally infected rabbits, using serotype A:12 antigen, revealed 3 polypeptides with approximate molecular mass of 28, 30, and 37 kDa that consistently detected antibodies after P multocida-induced infection. Sera from rabbits naturally infected with either serotype, tested against serotype A:12 and A:3 antigens, detected the same polypeptides in both serotypes. Thus, immunologic reactivity to these polypeptides may be useful for serologic detection of P multocida infection. PMID- 1497179 TI - Stimulation and suppression of the oxygenation activity of porcine pulmonary alveolar macrophages by Actinobacillus pleuropneumoniae and its metabolites. AB - The effects of Actinobacillus (Haemophilus) pleuropneumoniae and its metabolites on the oxygenation activity of porcine pulmonary alveolar macrophages (PAM) were studied, using a chemiluminescence technique. Actinobacillus pleuropneumoniae strains of serotypes 2, 3, and 9 in a dose of 1, 10, and 100 colony-forming units/macrophage first stimulated the oxygen radical production of PAM. After having reached a peak value, oxygenation activity decreased, finally resulting in total suppression of PAM. All these effects were neutralized by homologous convalescent pig sera that had been adsorbed onto inactivated A pleuropneumoniae strains. Moreover, cross-neutralization was shown between serotypes 2 and 3. Inactivated A pleuropneumoniae strains did not influence the oxidative activity of PAM. Undiluted and lower dilutions of sterile A pleuropneumoniae culture supernatants were toxic for PAM, whereas higher dilutions of the supernatants stimulated oxygen radical production of the macrophages. These effects were heat sensitive and were neutralized by homologous convalescent pig sera. Cross neutralization was shown between serotypes 2 and 3. These findings indicated that stimulation and inhibition of the oxygenation activity of PAM are attributable to heat-sensitive metabolites produced by A pleuropneumoniae. PMID- 1497180 TI - Double-antibody sandwich enzyme-linked immunosorbent assay and immunoblot analysis used for control of caseous lymphadenitis in goats and sheep. AB - A double-antibody sandwich ELISA for detection of antibodies directed against the exotoxin of Corynebacterium pseudotuberculosis, the cause of caseous lymphadenitis (CL) in small ruminants, was developed. A concentrated exotoxin was used. For interpretation of ELISA results, these sera were tested: sequentially obtained sera of C pseudotuberculosis-inoculated goats and sheep that were monitored for 68 weeks; sequentially obtained sera from 80 goats of 3 flocks with CL; sera from 652 goats of 7 flocks without CL; sera from 160 sheep of 4 flocks without CL; and 2,265 caprine and 208 ovine sera submitted for diagnostic testing. Data regarding the infection status and history of 10,454 of the 23,302 animals were collected after testing; most of these were goats that had been part of a CL control program. Specificity and sensitivity of the ELISA were nearly 100%. Subsequently, 31,978 animals from which no data on infection status of flocks had been collected were then tested. It was concluded that the ELISA is a useful diagnostic test for CL eradication programs. Sera with doubtful or inconclusive ELISA results were examined by use of immunoblot analysis. Proteins from C pseudotuberculosis culture supernatant were separated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and blotted onto nitrocellulose. Six proteins with molecular mass of 68, 65, 39, 38, 31, and 29 kDa reacted with sera from goats and sheep with experimentally induced or naturally acquired infection. Immunoblot analysis was valuable in classifying sera with doubtful or inconclusive results by ELISA. PMID- 1497181 TI - Antigenic variation of Mycoplasma gallisepticum, as detected by use of monoclonal antibodies. AB - A panel of monoclonal antibodies (MAb) developed against Mycoplasma gallisepticum strain PG31 was used to probe the antigenic profiles of 5 recognized strains (PG31, R, S6, F, A5969) and 6 field isolates of M gallisepticum. Monoclonal antibody G9 predominantly recognized antigens at apparent molecular mass positions of 90 to 98 kDA. The MAb reacted with all strains and isolates, but the molecular mass position of the antigens varied among some mycoplasmas. Monoclonal antibody G12 reacted with all strains and isolates of M gallisepticum and had an identical banding pattern. However, MAb G10 and G11 reacted selectively only with a limited number of strains and/or isolates. Surface distribution of the MAb recognized antigens was revealed by immunoelectron microscopy. Partial physicochemical characterization of MAb G9-recognized antigens identified glycopeptide characteristics. Monoclonal antibody G9 reacted with surface antigens and, hence, participated in agglutination of M gallisepticum. However, the degree of agglutination varied among the various strains and isolates, indicating a quantitative or conformational limitation or an alteration in the anomeric expression of the epitopes. Antigenic variation in M gallisepticum may be mediated by immunologic selective pressures, or a proclivity for habit niche in the host. PMID- 1497183 TI - Temporal effects of plasmapheresis on serum proteins in horses. AB - The temporal response of blood and serum proteins to chronic plasmapheresis was determined in 8 horses used in a commercial antibody enterprise. Plasmapheresis of between 4 and 11 L induced significant decreases in total protein, albumin, and IgG values. With the exception of a high hematocrit value for the first postplasmapheresis blood sample, there were no changes in erythrocyte or leukocyte measurements, and no changes in the proportions of serum protein in an electrophoretic profile. Regression equations generated for recovery of proteins after plasmapheresis indicated a return to preplasmapheresis values of total protein and albumin at approximately 1 month. Complications of repeated plasmapheresis were not detected when plasma extractions were done between 7 and 19 times at 30-day intervals. PMID- 1497182 TI - Myoelectric activity of the small intestine in enterotoxin-induced diarrhea of calves. AB - Electrodes were surgically implanted at 15-cm intervals in the jejunum and ileum of 4 healthy neonatal calves so that myoelectric activity could be recorded on 2 consecutive days. On the first day, each calf received a control treatment, and myoelectric activity was recorded for 340 minutes. Phase I was recorded for a mean of 175.8 +/- 22.8 minutes (51.5%), phase II for 124 +/- 27.4 minutes (36.5%), and phase III for 40.3 +/- 6 minutes (11.9%). On the second day, each calf was treated with approximately 200 micrograms of heat-stable enterotoxin (STa) of Escherichia coli orally. All calves developed diarrhea after the administration of STa. Phase I was recorded for a mean of 92.5 +/- 42.3 minutes (27.2%), phase II for 227.3 +/- 52.5 minutes (66.9%), and phase III for 20.3 +/- 11.4 minutes (6.0%). Increase in phase II and decrease in phases I and III after STa administration were significant (P less than 0.05). Duration of the migrating myoelectric complex was longer after STa administration (median, 64 minutes), compared with the control treatment (median, 54 minutes). Minute rhythms, recorded on the day of toxin administration, ranged from 49 to 153 minutes. There was no difference between the number of migrating action potential complexes on the control days (range, 1 to 10), compared with those on treatment days (range, 1 to 14). These findings are suggestive that enterotoxin-induced diarrhea of calves is accompanied by increased total spiking activity and minute rhythms in the distal portion of the jejunum and ileum. PMID- 1497184 TI - Parasympathetic influence on the arrhythmogenicity of graded dobutamine infusions in halothane-anesthetized horses. AB - We investigated the influence of parasympathetic tone on the arrhythmogenicity of graded dobutamine infusions in horses anesthetized under clinical conditions. Six horses were used in 9 trials. Two consecutive series of graded dobutamine infusions were given IV; each continuous graded dobutamine infusion was administered for 20 minutes. The dobutamine infusion dosage (5, 10, 15, and 20 micrograms/kg of body weight/min) was increased at 5-minute intervals. Isovolumetric saline solution vehicle (v) or atropine (A; 0.04 mg/kg) was administered IV, or bilateral vagotomy (VG) was performed as a treatment before the second series of dobutamine infusions. Treatment was not administered prior to the first dobutamine infusion. Significant interaction between treatment and dosage of dobutamine infusion existed for differences from baseline for mean arterial pressure, systolic arterial pressure, diastolic arterial pressure, heart rate, and cardiac index at dosages of 5 and 10 micrograms of dobutamine/kg/min, given IV and for heart rate at dosage of 15 micrograms of dobutamine/kg/min, given IV. Results for group-V horses were different from those for group-A and group-VG horses, but were not different between group-A and group-VG horses in all aforementioned cases, except for heart rate and cardiac index at dosage of 5 micrograms of dobutamine/kg/min, given IV. Normal sinus rhythm, second-degree atrioventricular block, and bradyarrhythmias predominated during low dobutamine infusion rates during the first infusion series (nontreated horses) and in group V horses during the second infusion series. Only tachyarrhythmias were observed during the second infusion series in the horses of the A and VG groups.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1497185 TI - Urethral pressure response to alpha-adrenergic agonist and antagonist drugs in anesthetized healthy male cats. AB - Urethral smooth muscle tone in response to treatment with phenylephrine, a selective alpha 1-adrenergic receptor agonist, and prazosin a selective alpha 1 adrenergic receptor antagonist, was evaluated in 12 anesthetized healthy adult sexually intact male cats. Intravenous administration of prazosin (20 to 30 micrograms/kg of body weight) decreased the average preprostatic and prostatic intraurethral pressure, compared with baseline and postphenylephrine (20 to 30 micrograms/kg) administration, values. Neither prazosin nor phenylephrine administration had an effect on functional urethral length. Results have implications for the pharmacologic management of lower urinary tract disorders in male cats. PMID- 1497186 TI - Evaluation of the Doppler ultrasonic method of measuring systolic arterial blood pressure in cats. AB - The accuracy of the Doppler technique for indirect systolic blood pressure measurement was assessed in 16 anesthetized cats. Eight cats were anesthetized with isoflurane and 8 were anesthetized with halothane. Anesthetic depth and mode of ventilation were varied to obtain a wide range of arterial blood pressure. A Doppler transducer was placed on the palmer surface of the left forelimb over the common digital branch of the radial artery to detect blood flow, and a blood pressure monitoring cuff with a width 37% the limb circumference was placed half way between the elbow and the carpus. To enable direct arterial pressure measurements, the left femoral artery was catheterized and the blood pressure waveforms recorded simultaneously. Systolic blood pressure measured by use of the Doppler ultrasonic technique was significantly lower than that obtained from the femoral artery catheter. Using linear regression, we determined a clinically useful calibration adjustment for Doppler indirect blood pressure measurement in cats: femoral systolic pressure = Doppler systolic pressure + 14 mm of Hg. PMID- 1497187 TI - Efficacy of two formulations of albendazole against liver flukes in cattle. AB - Albendazole (10 mg/kg of body weight) was administered as a drench suspension or as a feed additive to 24 cattle with naturally acquired infections of Fasciola hepatica and Fascioloides magna. Cattle were euthanatized 16 to 30 days after treatment, and the number of viable flukes was counted. Viable F hepatica and F magna were decreased by 91.4% and 70.6% for drench administration and by 82.9% and 71.9% for the feed additive treatment, respectively. There was no significant difference between the efficacy of the 2 formulations in decreasing viable fluke numbers, compared with untreated controls. PMID- 1497188 TI - Cytologic findings of tracheobronchial aspirates from 66 thoroughbred racehorses. AB - Tracheobronchial aspirates obtained from 66 healthy Thoroughbred racehorses in training at the same track were examined. Twenty-seven percent of the horses had greater than 20% neutrophils in the aspirate. Eosinophils, mast cells, giant cells, and Curschmann's spirals of mucus were observed in 94, 83, 65, and 42% of the horses, respectively. Hemosiderophages were observed in 86% of the horses, half of which had previous confirmation of exercise-induced pulmonary hemorrhage. Although fungal elements were seen in 70% of the horses, bacteria were detected in only 3% of the horses. The authors conclude that inflammatory airway disease is widespread in the racing Thoroughbred population. PMID- 1497189 TI - Intestinal permeability in pigs during rotavirus infection. AB - Macromolecular permeability of the small intestine was tested in four 3-week-old gnotobiotic pigs inoculated with porcine rotavirus strain RV277 (group A). Pigs were administered 125I-labeled polyvinylpyrrolidone (molecular weight [mol wt], 40,000) orally 1 day before and 2 and 24 hours after virus inoculation, and blood samples were obtained every 6 hours. Eight hours after rotavirus inoculation, pigs had watery diarrhea. Increased permeation of 125I-labeled polyvinylpyrrolidone was not observed after clinical signs of infection had developed. Serum total protein and urea nitrogen concentrations increased slightly at the end of the study, probably as a consequence of dehydration. Differences in blood glucose concentration were not seen. At 48 hours after viral inoculation, macromolecular permeability was tested morphologically by injecting horseradish peroxidase (mol wt, 40,000) into the jejunal lumen just distally to the ligamentum colicoduodenale. After an incubation period of 20 minutes, small segments of jejunum were obtained for stereomicroscopic, histologic, and ultrastructural investigations. Moderate hyperregenerative villus atrophy was found. Ultrastructural changes of the villus epithelium were minor, and increased macromolecular permeation was not observed. PMID- 1497190 TI - Risk factors for abomasal volvulus and left abomasal displacement in cattle. AB - A hospital-based case-control study was conducted to evaluate and compare risk factors for abomasal volvulus (AV) and left displaced abomasum (LDA) in cattle. Medical record abstracts were derived from 17 North American veterinary schools by the Veterinary Medical Data Program for all cattle admitted between Jan 1, 1977 and Dec 31, 1986, and for those with a diagnosis of AV or LDA. From a total of 108,956 individual cattle records, 1,036 cases of AV and 7,695 cases of LDA were identified, with a ratio of LDA to AV cases of 7.4 to 1. In-hospital mortality was 23.5% for AV and 5.6% for LDA. Age, breed, gender, and season each had significant (P less than 0.05) effects on risk for AV and LDA. Risk for AV and LDA increased with increasing age, with greater risk in cattle aged 4 to 7 years. Dairy cattle were at higher risk of developing AV (adjusted odds ratio, 36.4) and LDA (adjusted odds ratio, 95.2) than were beef cattle. The odds of AV in Brown Swiss cattle were significantly (P less than 0.0001) lower, and the odds of LDA in Guernsey cattle were significantly (P less than 0.0001) higher than those in Holstein cattle. Female cattle were also at higher risk of developing AV (adjusted odds ratio, 3.3) and LDA (adjusted odds ratio, 29.1) than were male cattle. The odds of AV and LDA varied considerably throughout the year, with the lowest number of cases observed in autumn. Seasonal development of AV differed significantly (P less than 0.0001) from that of LDA, with the odds of AV and LDA being highest in January and March, respectively.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1497191 TI - Evaluation of intra-articularly administered sodium monoiodoacetate-induced chemical injury to articular cartilage of horses. AB - Three doses of sodium monoiodoacetate (MIA) were used to induce degenerative changes in articular cartilage in middle carpal joints of horses. Twelve young (2 to 5-year-old) horses, free of lameness, were randomly allotted to 3 groups. One middle carpal joint of each horse was injected with 0.9% NaCl solution (control joint). The contralateral middle carpal joint was injected with 0.09 mg of MIA/kg of body weight (group 1); 0.12 mg/kg (group 2); or 0.16 mg/kg (group 3). After MIA administration, horses were allowed ad libitum exercise in a 2-acre paddock for 12 weeks. At the end of the study, gross and microscopic tissue changes were evaluated and biochemical analyses of articular cartilage were done. Grossly, diffuse partial-thickness articular cartilage lesions were observed in group-2 (n = 2) and group-3 (n = 4) horses, but not in group-1 horses. Articular cartilage uronic acid content was significantly (P less than 0.03) decreased in all MIA injected joints, compared with controls. Articular cartilage matrix staining with safranin-O was decreased in 3 of 4 MIA-injected joints of group-1 horses and in all MIA-injected joints of group-2 and group-3 horses, compared with controls (P less than 0.06). Microscopic degenerative changes in articular cartilage were not significantly different between MIA-injected and control joints in group-1 horses, but were increased (P less than 0.06) in all MIA-injected joints of group 2 and group-3 horses, compared with controls. Qualitatively, decreased matrix staining and degenerative changes were more severe in group-3 horses. On the basis of articular cartilage gross and microscopic changes, as well as biochemical changes, 0.12 mg of MIA/kg injected intra-articularly was determined to induce moderate degrees of articular cartilage degeneration. This model of chemically induced articular cartilage injury could be useful for evaluating treatment effects of anti-arthritic drugs in horses. PMID- 1497193 TI - Histomorphometric analysis of the rumen of sheep during development. AB - Histomorphometric and scanning electron microscopic analyses were carried out on 74 embryos and fetuses and 20 sheep (early postnatal to adult age). Histodifferentiation of the rumen took place at 33 days of fetal life. Ruminal pillars were observed at 42 days, and at 61 days, ruminal papillae appeared as evaginations of the epithelial stratum basale. Neutral mucopolysaccharides first appeared in epithelial cells at 46 days of fetal life; thereafter, numbers decreased gradually and subsequently stabilized in postnatal life. Acid mucopolysaccharides, mucins, and mucoid compounds were not detected. Age and diet were recognized as factors that determine the structure of the ruminal mucosa. Growth curves and formulas were set out for each tissue layer. PMID- 1497192 TI - Evaluation of support bandaging during measurement of proximal sesamoidean ligament strain in horses by use of a mercury strain gauge. AB - Liquid mercury strain gauges were implanted in the forelimb proximal sesamoidean ligaments (PSL) of 8 adult horses. The gauges measured PSL strain while horses were standing with or without external support. In 6 of the horses, the gauges also measured PSL strain in horses at a walk, with or without external support. Gauges were enclosed within sliding polypropylene tubes to prevent nonaxial deformation. Each gauge was placed in 1 arm of a low-resistance half-bridge circuit. To provide temperature compensation, a dummy gauge was placed in the adjacent arm of the bridge circuit and was implanted next to the active gauge in the surrounding fascial tissue. External support included fiberglass cast support (CAST), dorsal fetlock splint support (DFS), support wraps of 3 bandage materials (SW1, SW2, and SW3), and support wrap with caudal splint (SW4). The cast was applied, with the fetlock and foot in weightbearing position, from the proximal portion of the metacarpus distal to and including the foot. The DFS was applied by placing the cranial half of the fiberglass cast on the dorsal aspect of the instrumented limb. The SW1, SW2, and SW3 were applied in a figure-8 pattern around the fetlock, using 50% of the linear stretch capacity of the bandage material, with the horse standing squarely on all 4 limbs. The SW4 was applied identically to the other support wraps, with the exception of addition of a flexible caudal splint incorporated in the support wrap. Mean maximal strain while standing (epsilon S) without external support for 8 horses was 6.0% (range, 3.8 to 7.5%).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1497194 TI - High-resolution computed tomography of the mammalian lung. AB - High-resolution computed tomography (HRCT) was performed in 21 isolated animal lungs, from 4 mammalian species (pigs, rabbits, dogs, sheep). Gross and subgross central and peripheral lung morphology was determined by HRCT. Three distinct types of lungs can be identified, principally based on the extent of interlobular septal development; the relationship of major vessels to airways; and the thickness of the visceral pleura. Type-I lung is found in pigs, sheep, and cattle; type-II lung is found in rabbits, dogs, cats, and monkeys; and type-III lung is found in human beings and horses. These mammalian lungs were compared with human lungs. The potential use of HRCT to investigate specific human lung diseases in the aforementioned species also was considered. PMID- 1497195 TI - Effects of dialyzable lymph node extracts on lymphoblast proliferative capacity of blood mononuclear cells in cattle with chronic paratuberculosis. AB - Dialyzable lymph node extracts (DLE) containing transfer factor prepared from calves sensitized to Mycobacterium paratuberculosis and keyhole-limpet hemocyanin (KLH) were administered to 4 adult cows with chronic paratuberculosis. Cutaneous delayed hypersensitivity, lymphocyte blastogenesis, monocyte migration inhibition, and lymphoblast proliferative capacity as a reflection of interleukin 2 (IL-2) activity were measured in response to M bovis purified protein derivative, johnin, and KLH before and after treatment with DLE. Change in cutaneous delayed hypersensitivity was not evident after DLE treatment. Alterations in histologic features of pre- and posttreatment sections of ileum and mesenteric lymph nodes were not detected. Lymph node extract treatment significantly (P less than 0.05) increased IL-2 activity and migration-inhibition in response to johnin and KLH in vitro. Treatment had no effect on lymphocyte blastogenesis. The data indicate that cattle with chronic paratuberculosis may benefit from DLE treatment, by virtue of increased IL-2 activity, and that effects of DLE are at least partially mediated by an increase in IL-2 activity. PMID- 1497196 TI - Systemic toxicosis associated with azathioprine administration in domestic cats. AB - Five cats were treated with an azathioprine suspension (2.2 mg/kg of body weight on alternate days) and 2 cats were given vehicle (controls) for 9 weeks. Complete blood and platelet counts and serum biochemistry variables were monitored weekly. Bone marrow aspirates were evaluated every 3 weeks, and core bone marrow biopsy was performed at the end of the study. Profound neutropenia (less than 600 cells/microliters) was observed in all treated cats, and 1 cat developed pancytopenia. Treatment was discontinued if the WBC count was less than 3,000 cells/microliters. Four weeks after discontinuation of azathioprine, 1 treated cat again was given azathioprine at a lower dosage (1.1 mg of azathioprine/kg on alternate days) and neutropenia recurred within 2 weeks. During treatment, 3 cats developed thrombocytosis, and 2 developed thrombocytopenia. In 4 of 5 cats, neutropenia and thrombocytopenia resolved when azathioprine was discontinued. Bone marrow cytologic examination during treatment revealed reduction of the neutrophil line, with relative increase in monocytes. Core bone marrow biopsy at the completion of the study revealed hypocellular marrow with marked decrease in the myeloid series in cats given azathioprine. One of the cats that was treated with azathioprine had a hypercellular marrow with increased numbers of mature granulocytes and precursors; however, azathioprine had been discontinued 3 weeks prior to biopsy. Alterations in serum biochemical variables were not associated with azathioprine. Two cats that were treated with azathioprine developed respiratory tract infections, and 1 of them was euthanatized during the study. PMID- 1497197 TI - Effects of fluoride on secretory and postsecretory phases of enamel formation in sheep molars. AB - Effect of fluoride was assessed on molars during and after mineralization. Two groups of 7 sheep each were dosed orally with 3.5 mg of fluoride/kg of body weight daily for 4 months (from 5 to 9 months after birth). Sheep of the first group were slaughtered immediately after fluoride administration; those of the second group were slaughtered 4 months later at the age of 13 months. Three control groups of 7 sheep each were slaughtered at 5 months (to determine the state of the teeth at the beginning of fluoride administration), and at 9 and 13 months. During fluoride administration, plasma fluoride concentration rapidly increased to about 0.50 microgram/ml; after fluoride administration, it stabilized at 0.20 microgram/ml in treated sheep, whereas controls had concentration of 0.10 micrograms/ml (P less than 0.01). Parts of the molars that were in the process of mineralization during fluoride administration (mainly second molars) had thinning enamel, with pits, mainly close to the apex, marked decrease in hardness throughout the layer (less than 100 Vickers U, compared with 240 Vickers U), and fluoride accumulation twice as high as that in controls (1,000 to 2,500 mg/kg [dry weight]). Fluoride accumulation was higher in dentine (2,700 to 4,200 mg/kg), but hardness was less affected. On parts of the molars that were already mineralized (mostly, the first molar), changes in the appearance of enamel and cementum, decreased hardness (less important than in teeth during mineralization) affecting outer enamel more than inner enamel, high fluoride concentration (4,000 to 5,500 mg/kg [dry weight]) in outer enamel extending over 200 microns were observed.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1497198 TI - Blood types in cattle of Iberian ancestry and in Holsteins at various altitudes. AB - Gene frequencies of RBC antigens were determined in Holsteins and Colombian (criollas) cattle living at 3,000 m, and in cattle descended from fighting bulls (Vacas de lidia) living at 2,500 m. These frequencies were compared with those of Holsteins, cattle native to Florida (scrub cattle), longhorns, and native cattle from Brazil (caracu cattle) living at sea level. The criollas, Vacas de lidia, scrub cows, longhorns, and caracu are descendants of original Iberian stock introduced to the Americas. We found that despite common ancestry (scrub cattle, long-horns, criollas, and caracu), genetic differences may have been derived through years of demographic isolation. The most remarkable blood-group differences were found in the high prevalence of the B system phenogroup (heritable group of antigenic factors) BQA'G'34 in the Vacas de lidia, and of the S system phenogroup U1H' in these cattle and in caracu. Furthermore, the gene frequencies differed in the Holsteins maintained at moderately high altitude (descended from Holsteins kept at sea level), and may have been reflective of the need to adapt to moderately high altitude and chronic hypoxemic conditions. Blood group polymorphism was found in all groups of cattle, although it was reduced in the Vacas de lidia, possibly because their breeding has been carefully controlled and they appear to be highly inbred. PMID- 1497200 TI - Fibrinogen-degrading proteins from Haemonchus contortus used to vaccinate sheep. AB - Sixteen nonsibling sheep, approximately 12 months old, that were raised in a helminth-free environment, were used for 2 protection studies 6 months apart. Sheep were vaccinated weekly for 5 weeks by IM injection of fibrinogen-degrading proteins derived from the intestinal tract of adult Haemonchus contortus. Ten days after the last vaccination, sheep were given 2,500 infective H contortus larvae by intraruminal injection. Vaccinated sheep produced specific antibodies, and were protected from the worm challenge. Significant differences in mean fecal worm egg counts for 56 days after worm challenge, in mean numbers of H contortus worms, and female fecundity ratios at necropsy were detected in vaccinated sheep, compared with those in control sheep. These data suggest that the fibrinogen degrading proteins have a protective role in vaccination of sheep against H contortus. PMID- 1497199 TI - Serum lipoprotein concentrations and hepatic lesions in obese cats undergoing weight loss. AB - Serum lipoprotein concentrations, routine serum biochemical values, and morphologic changes of the liver were evaluated in cats undergoing weight loss. Food was withheld from 6 obese and 6 control cats for 3 days (days 0 to 2), followed by feeding 50% of previous food intake for 26 days (days 3 to 28). Percutaneous liver biopsy specimens were obtained from all cats on days 0, 7, 14, and 28. Blood samples for serum biochemical analysis and lipoprotein profiles were obtained on days 0, 3, 7, 14, and 28. All cats lost weight throughout the study, and none developed signs of clinical illness, including those of idiopathic hepatic lipidosis syndrome. Serum total cholesterol concentrations decreased initially in all cats, but rapidly returned to normal after day 3 in obese cats, suggesting altered cholesterol metabolism during dietary restriction. Low-density lipoprotein concentrations decreased throughout the study in control cats, but were unchanged in obese cats. Examination of liver biopsy specimens from each cat revealed minimal lipid accumulation in all specimens, although some specimens contained hydropic degeneration. PMID- 1497201 TI - Evaluation of the dermal effects of cast padding in coaptation casts on dogs. AB - Three configurations of cast padding and no cast padding were evaluated for their effects on skin in dogs. Padding was placed over bony prominences, between bony prominences, and over both areas for full-length padding under short-limb walking casts applied to 1 pelvic limb of Greyhounds. Evaluations were performed by pressure measurement over the calcaneal tuberosity, measurement of skin thromboxane B2 (TxB2) concentrations in skin over bony prominences, and measurement of plasma TxB2 concentrations. Pressure studies were performed to evaluate cutaneous pressures related to no cast padding and various configurations of cast padding. Concentrations of TxB2 in the skin were determined to evaluate the skin inflammatory effects of no padding and the padding configurations, and TxB2 concentrations in the plasma were analyzed to ascertain whether they could be used to predict impending dermal pressure lesions. Flexion of casted limbs revealed the greatest pressure over the calcaneal tuberosity with full-length cast padding. This was followed in decreasing order by no cast padding, padding over the prominences, and padding between the prominences. Compared with all other bony prominences and padding configurations, TxB2 skin concentrations were significantly higher over the calcaneal tuberosity when no padding was used and over the lateral base of metatarsal V when padding was placed between the prominences. Over the calcaneal tuberosity, this was attributed to the sharpness of the prominence and its potential for movement. This high TxB2 concentration corresponded to the high pressure found in the pressure studies. Over the lateral base of metatarsal V, the increase in TxB2 concentration was related to the mass of the prominence and the tendency for localized padding to settle around the area.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1497202 TI - Serum and skin concentrations after multiple-dose oral administration of trimethoprim-sulfadiazine in dogs. AB - Six healthy adult mixed breed dogs were each given 5 oral doses of trimethoprim (TMP)/sulfadiazine (SDZ) at 2 dosage regimens: 5 mg of TMP/kg of body weight and 25 mg of SDZ/kg every 24 hours (experiment 1) and every 12 hours (experiment 2). Serum and skin concentrations of each drug were measured serially throughout each experiment and mean serum concentrations of TMP and SDZ were determined for each drug for 24 hours (experiment 1) and 12 hours (experiment 2) after the last dose was given. In experiment 1, mean serum TMP concentration was 0.67 +/- 0.02 micrograms/ml, and mean skin TMP concentration was 1.54 +/- 0.40 micrograms/g. Mean serum SDZ concentration was 51.1 +/- 12.2 micrograms/ml and mean skin SDZ concentration was 59.3 +/- 9.8 micrograms/g. In experiment 2, mean serum TMP concentration was 1.24 +/- 0.35 micrograms/ml and mean skin TMP concentration was 3.03 +/- 0.54 micrograms/g. Mean serum SDZ concentration was 51.6 +/- 9.3 micrograms/ml and mean skin SDZ concentration was 71.1 +/- 8.2 micrograms/g. After the 5th oral dose in both experiments, mean concentration of TMP and SDZ in serum and skin exceeded reported minimal inhibitory concentrations of TMP/SDZ (less than or equal to 0.25/4.75 micrograms/ml) for coagulase-positive Staphylococcus sp. It was concluded that therapeutically effective concentrations in serum and skin were achieved and maintained when using the manufacturer's recommended dosage of 30 mg of TMP/SDZ/kg (5 mg of TMP/kg and 25 mg of SDZ/kg) every 24 hours. PMID- 1497203 TI - House takes stand against harassment, discrimination. PMID- 1497204 TI - Guideline released on pressure ulcers. PMID- 1497205 TI - If no one wins the election.... PMID- 1497206 TI - ANA, WSNA denounce Cammermeyer discharge. PMID- 1497207 TI - Nurse takes stand on discrimination. Interview by Mandy Mikulencak. PMID- 1497208 TI - ANA testimony focuses on rural health care. Interview by Cindy Yeast. PMID- 1497209 TI - A day in the life of a nurse. Role of transplant nurse includes education. PMID- 1497210 TI - Styles attends World Health Assembly. Interview by Patricia McCarty. PMID- 1497211 TI - Public rates nursing's agenda as second most believable plan. PMID- 1497212 TI - RN shortage seen for 21st century. As I see it. PMID- 1497213 TI - United, autonomous, political, powerful. PMID- 1497214 TI - RN statistics--do they matter? PMID- 1497215 TI - Missouri takes a look at nursing's future. Interview by Mandy Mikulencak. PMID- 1497216 TI - How to keep mature, skilled nurses. Interview by Patricia McCarty. PMID- 1497217 TI - Perceiving and re-perceiving objects. AB - A number of experiments exploring priming effects and automatization in the perception of novel objects are described, and a framework for understanding the benefits and costs of re-perceiving previously seen objects is proposed. The suggestion is that perceiving an object creates a temporary representation in an object file that collects, integrates, and updates information about its current characteristics. The contents of an object file may be stored as an object token and retrieved next time the object appears. This facilitates its re-perception when all of the attributes match and may impair it if some are changed. Thus, the world molds our minds to capitalize on earlier experiences but at the same time leaves us able readily to detect and represent any novel or unexpected objects and events. PMID- 1497218 TI - Scientific rewards and conflicts of ethical choices in human subjects research. AB - The primary responsibility of the American Psychological Association's (APA) Committee on Standards in Research (CSR) is to advise the APA on issues and standards related to the protection of human participants in psychological research. A related goal is to enhance the use of good ethical practices by APA members. The purpose of this article is to foster the view of research ethics not as an affront to the integrity of sound research, but as opportunities for scientific rewards, including increased understanding of the meaning of data, enhanced recruitment, and the inclusion of more representative samples. Three ethical practices are discussed as examples of this general premise: respect for confidentiality, use of debriefing, and assurance that participants are noncoerced volunteers. The Committee's intent is to promote consideration of these issues, not to promulgate specific guidelines or procedures. PMID- 1497219 TI - [Adolescents and legal drugs]. PMID- 1497220 TI - [Attitude towards parents after the death of their newborn infant in a neonatal unit]. AB - We have analyzed the neonatology team's actions, as well as the parent's reactions, after the death of a newborn baby in the Intensive Care Unit. A questionnaire was drawn-up and sent to 180 parents of decreased newborn babies in order to get to know their opinions about certain aspects related to their experience in the hospital. Only 49 out of the 180 (27.2%) questionnaires were sent back. From their answers, we would like to stress their positive opinion regarding both the medical care (95%) and the information that they received (93%). The suggestion that the hospital should have a trained team of trained professionals available to provide psychological support in such situations was made in 95.9% of the questionnaires. This analysis has justified changes in our team's procedure when confronted with newborn deaths. PMID- 1497221 TI - [Clinical and laboratory indicators of etiology of diarrhea]. AB - Several clinical symptoms and laboratory findings from 352 pediatric patients, seen in the Emergency Room for acute diarrhea, were evaluated in order to develop a method to predict the bacterial etiology of the diarrhea. According to the microbiology findings, the patients were classified into two groups: proven bacterial diarrhea and diarrhea of another etiology. Among all clinical symptoms recorded, only the following were found to be useful for the prediction score: fever greater than 38 degrees C (8 points), fecal mucus (8 points), over fecal blood (6 points) and the presence of fecal leukocytes in a wet mount (7 points). An alternative score useful for outpatients was developed that does not include a score for the wet mount. When the fecal leukocyte score was included and a cutoff value of 20 points was assigned, a sensitivity of 74% and a specificity of 83% were obtained. When the score for the fecal leukocytes was excluded and a cutoff value of 13 points assigned a sensitivity of 84% and specificity of 59% were obtained. These rapid and simple scores may be useful methods for predicting acute bacterial diarrhea in children. PMID- 1497222 TI - [Suicide attempts in childhood and adolescence: risk factors]. AB - The rate of suicides among adolescents has shown a disturbing increase during the last decades, becoming one of the most important issues in child and adolescent psychiatry. Suicide attempts increase steadily with age, especially among girls, who grossly out-number boys in the number of attempted suicides. However, clinicians face a difficult dilemma in identifying those children who are at the greatest risk for medically serious suicide attempts. This paper presents the results of the risk factors studied in 30 children and adolescents who have made suicide attempts compared to a matched control group. A broken home or loss of the father, alcoholism, disturbed upbringing and family relationships, previous suicide attempts, school failure and social isolation of the family were among the risk factors most frequently present. PMID- 1497223 TI - [Bone marrow transplantation in malignant diseases in childhood using reverse isolation technics: evaluation of results]. AB - Between July 1985 and March 1990, 31 pediatric patients with neoplastic diseases underwent bone marrow transplantation (22 allogenic and 9 autologous). Routine reverse isolation techniques with sterilization of the gastrointestinal tract were used in all cases. Of these patients, 55% had fever and 32% had a documented infection. In allogenic bone marrow transplants, 23% developed graft-versus-host disease, grade I-IV. The incidence of infection and graft-versus-host disease compares favorably with other published reports from centers utilizing laminar air flow rooms during bone marrow transplantation. This suggest that standard reverse isolation techniques may be used without increasing the morbidity and mortality in these patients. PMID- 1497224 TI - [Evaluation of the Andalusia Vaccination Program in the Sierra de Cadiz Sanitary District]. AB - One of the foundations for good child care is the application of a vaccination program. With this report we evaluate the vaccination coverage (January 1991) of a group of children (1319), born during 1988 between January 1st and October 1st, in the Sierra of the District of Cadiz. Our results show that 87.64% participated in the Vaccination Program. The first vaccination was received by 80.06% of these children. This rate decreased as we advanced through the vaccination calendar, reaching 76.34% for the measles/mumps/rubella vaccination and 66.71% for the vaccination at 2 years of age. Therefore, one-third of this child population did not complete the vaccination schedule. The most frequently found complication was a local reaction, whereas the counter-indication most frequently observed was an acute infectious illness. PMID- 1497225 TI - [Pneumococcal meningitis in the infantile population of Cantabria]. AB - A retrospective study of pneumococcal meningitis was carried out. This study included 22 cases of this illness that occurred in 17 pediatric patients in Cantabria between 1977 and 1990, inclusive. Three children suffered from recurrent meningitis. The age range of the patients was 0.3-14 years, with a mean age of 4 years. Of these cases, 77.4% occurred in the winter or spring. In 14 cases of meningitis (63.6%), corresponding to 9 patients, underlying pathology was observed: cranial fracture, occipital dermoid cyst, splenectomy, congenital cardiopathy, epilepsy and gastroduodenal "situs inversus". The isolated pneumococci were found to be resistant to penicillin and chloramphenicol in 4 cases. One patient suffered from septic shock. The outcome was complete recovery in 19 cases (86.4%), recovery with sequelae (deafness and epilepsy, respectively) in 2 cases (9.1%) and death in another 2 cases. CSF protein levels elevated above 150 mg/dl and the absence of glucose in the CSF were found to be the most useful analytical indicators of the seriousness of the illness. PMID- 1497226 TI - [Prognosis in recurrent peripheral idiopathic facial paralysis in childhood]. AB - Fifty-nine cases of idiopathic peripheral facial palsy were diagnosed in our unit during the period from January 1, 1984 to December 31, 1989. During follow-up examinations we observed a relapse in eleven cases, corresponding to 18.6% of the patients. Nine patients suffered a relapse once, one case twice and another case four times. The children that presented more than one recurrence have later shown functional sequelae, both clinical and neurophysiological. We conclude that in our series of patients relapse of facial palsy is a factor that worsens the prognosis for recovery. Furthermore, the existence of facial palsy in the family history leads to a greater risk of a recurrence. PMID- 1497227 TI - [Esophageal atresia and associated anomalies]. AB - Twenty-seven newborns with esophageal atresia were reviewed for the presence of other congenital associated anomalies. The incidence of esophageal atresia was 2.6 cases for every 10,000 live births. Associated anomalies were present in 59.25% of these cases. Cardiac malformations were the most frequent associated defect (40.7%). Ten infants met the criteria for VACTERL association. The birth weights and gestational ages were similar for both the surviving and deceased infants. Broncho-aspiration was the only significant factor associated with mortality: 75% of the infants who had broncho-aspiration died, versus only 26.3% if aspiration was not present. When associated anomalies were present, mortality was 56.25%, whereas only 18.18% of the infants without these anomalies died (p = 0.055). We conclude that only broncho-aspiration and associated anomalies relate to mortality in esophageal atresia, whereas the birth weight, the other Waterston's prognosis factor, is not important. PMID- 1497228 TI - [Renal function in diabetic children and adolescents. Relation to the duration and level of control of the disease]. AB - We have evaluated different aspects of the kidney function of 68 diabetic children and adolescents with the aim of estimating the prevalence of nephropathy and its influential factors. In addition, the kidney function is followed for an additional 18 months. The results are compared with those obtained from a group of healthy children of the same ages. No clinical nephropathy existed, with only 4 (5.97%) and 8 cases of incipient nephropathy and microalbuminuria, respectively, being demonstrated. The urinary albumin excretion rate (AER) is very clearly connected with the duration and the metabolic control of diabetes. Elevated values for AER were also observed in poorly controlled diabetics and those with prolonged evolution. Nevertheless, the last point may be secondary to the development of puberty, since with the same duration of diabetes (under 5 years), the proportion of pubertal patients with microalbuminuria is higher than that for prepubertal children. PMID- 1497229 TI - [Piriform sinus fistula, a new disease]. AB - Pyriform sinus fistula has recently been described as a new, rare and little known pathology. The process develops as latero-cervical suppurative adenitis or acute suppurative thyroiditis, usually on the left side. Radical surgery is mandatory to avoid recurrence. This congenital malformation must be present in the differential diagnosis of recurrent infectious cervical processes, especially in acute thyroiditis. The only curative treatment is complete exeresis of the fistula after meticulous dissection of the fistulous tract. We present three cases of this pathology. The diagnostic approach and surgical treatment are discussed. The recent literature on this topic is reviewed. PMID- 1497230 TI - [Congenital lobar emphysema]. PMID- 1497231 TI - [Paralysis of the third cranial nerve in a 4-year-old girl]. PMID- 1497232 TI - [Perianal fistula or rectal duplication?]. PMID- 1497233 TI - [Purpura fulminans]. PMID- 1497234 TI - [Tuberculous epididymitis in a child. Report of a case and review of the literature]. PMID- 1497235 TI - [Extraskeletal Ewing sarcoma. Report of a new case and revision of the subject]. PMID- 1497236 TI - [Intraparenchymatous cerebral hemorrhage and cranial asymmetry caused by an unusual perinatal trauma]. PMID- 1497237 TI - [Non-bacterial arthritis associated with varicella. Report of a case]. PMID- 1497239 TI - [Epidemiology of tumors of the respiratory tract in Italy]. PMID- 1497238 TI - [Benign myoclonus in early infancy]. PMID- 1497240 TI - [Epidemiology of malignant tumors of the larynx and lung]. AB - Respiratory tract cancers, unlike most other cancers, have known causes and are susceptible to primary prevention. According to a large population-based case control study in Southern Europe, over 90% of the present incidence of laryngeal cancer could be prevented by avoiding smoking and alcohol consumption. Most of the risk is attributable to tobacco, but reducing alcohol alone could still prevent a quarter of the cases. Tobacco smoking, on the other hand, explains 80 to 90% of lung cancer incidence in Italy. Other known causal factors include: occupational exposures, which, according to several studies, may account for one third of the cases in the highly industrialized areas of Northern Italy; environmental pollution; passive smoking; radon; and dietary factors. Factors associated to a diet rich in fruit and vegetables have been found to be protective for both larynx and lung cancer in several studies carried out in Italy and elsewhere. The factors associated to this diet may be a major determinant in the North/South gradient in incidence and mortality consistently observed in geographical and migrant studies on respiratory cancers in Italy. Cigarette smoking, however, remains by far the most important cause of respiratory cancer, and geographical and temporal trends in incidence can easily be interpreted in terms of market trends, both in Italy and worldwide. According to several population surveys in Italy, the prevalence of smokers in successive male cohort generations reached a maximum (almost 80%) in the 1920-1930 birth cohorts and decreased to about 60% among males born in the forties and fifties. In the same period, the mean number of cigarettes per day for smokers increased, and the age of starting smoking decreased; however, the market changed from unfiltered black tobacco to filtered low-tar cigarettes. This market trend is consistent with the observation of decreasing incidence and mortality of both larynx and lung cancer in young male cohorts and the persistent increase of both cancers in older males. As for women, the prevalence of smokers increased from less than 10% in the 1920's birth cohorts to over 30% among women born in the late forties. This is reflected by a steady increase of respiratory cancers mortality which, however, is still lower than the mortality for males. PMID- 1497241 TI - [Etiological epidemiology of tumors of the nasal cavities and the paranasal sinuses]. AB - Etiologically-oriented epidemiologic studies on cancer of the nasal cavities and paranasal sinuses have been carried out since the beginning of the century. These studies showed that several chemical agents (chromates, nickel compounds, isopropylic alcohol, and mustard gas), and two occupational exposures (wood dust in the furniture industry and exposure to leather in shoe factories) were causally associated with nasal cancer. An increased risk has also been associated with several occupations (i.e. metalworker, textile worker, construction worker, and farmer) even in the apparent absence of causal agents. The first reports of an increased risk of nasal cancer in woodworkers and leather workers in Italy date back to 1980. Subsequent studies have provided estimates of the relative risk, ranging from 3.0 to 11.0 among woodworkers and from 8.1 to 47.1 among leatherworkers. Increased risks have been associated to the metal industry (relative risk ranging from 3.1 to 5.9), the textile industry (ranging from 2.9 to 17.0), the mining and construction industry (ranging from 2.3 to 5.3), and the agricultural industry (ranging from 1.9 to 3.3); all of these estimates are time- and place-specific. Moreover, the estimates are not reliable because of the small sample size, resulting from the low occurrence of the disease. The etiologic fraction for the population, taking into account both verified and suspected carcinogenic exposures, ranges between 50% and 65% in males. Relatively few cases of nasal cancer (all of them occurring in woodworkers) have been notified for workman's compensation; woodworkers with nasal cancer have received monetary compensation in Italy since 1988. Nasal cancer is an often fatal but largely preventable disease. Several verified and suspected occupational exposures are associated with this neoplasm. The reduction of dust and fumes in the air of the above mentioned work environments is recommended for reducing the occurrence of this disease. PMID- 1497242 TI - [Use of mortality data for the study of the distribution of respiratory tract tumors in Italy: characteristics and quality of the data]. AB - This paper reviews Italian studies that deal with the accuracy of death certificates in patients with cancers of the respiratory system, particularly cancers of the larynx, lung, and pleura. These studies consider death certificates vs postmortem examinations, diagnoses histologically confirmed, and clinical and cancer registry records. The large number of cases cured by surgery is reflected in the lower levels of larynx cancers mortality vs incidence. Site misclassifications, and erroneous reports of cancer on death certificates for patients cured of the disease, lead to an overreporting of death certification vs autopsies. The death certificates for lung cancer have a high agreement with clinical diagnoses, but present underreporting when compared to autopsies, which frequently discover tumors at postmortem examination. Pleura cancer is often misclassified as lung cancer. Improvement in death certification over time could have influenced the observed increase in the mortality trend for this tumor. PMID- 1497243 TI - [Estimation of the impact of cigarette smoking reduction on mortality from tumors of the lung and larynx]. AB - In 1987, in Italy, 27,106 men and 4,159 women died from lung cancer or larynx cancer. Taking into consideration the smoking habits of the Italian population and the relative risks for pulmonary cancer, of smokers and ex-smokers versus nerve smokers, we estimate that 87% of deaths can be attributed to smoking. We know from previous studies that quitting smoking results in the reduction of the risk elapsed since quitting and that this reduction depends on the time and on the quantity of tobacco previously smoked before the cessation. We estimated the reduction in the number of deaths due to respiratory cancer if part of the population were to quit smoking. In males aged 35-74 years after 12 years, there would be 3,604 fewer deaths if 10% quit smoking and 11,915 fewer deaths if 100% quit smoking. PMID- 1497244 TI - [Trends in mortality from respiratory tract tumors in Italy, 1969-1987]. AB - Trends of Italian death certification for cancers of the lung, larynx, pleura and nasal sinuses were analyzed for both sexes in the period from 1969 to 1987. For lung and laryngeal cancer, the analyses have been conducted for broad geographical areas within Italy (North, Center and South). Mortality rates for males aged 35-44 years consistently decreased in the North; increased until the late 1970's, and then decreased in the Center; and consistently increased in the South. In the 45-54 age group, mortality rates peaked in all areas between the late 1970's and the early 1980's, subsequently decreasing. For ages over 54 years, the rates continued to increase even in the 1980's. Female lung cancer rates increased in all areas and in all age groups over 35 years. In the 25-34 years old age group the rates decreased in the North and tended to increase in the Center and in the South. Below age 50, the increases were proportional in the three areas, while for older ages the increase was greater in the North both in absolute and proportional terms. Cohort effects showed a general increase for the generations born up to 1930, in both sexes and in all geographical areas. Different trends were observed for cohorts born after 1940: decreasing for both sexes in the North, and steady for men and increasing for women in the other areas. From the mid 1970's, laryngeal cancer standardized rates for 35-64 age group decreased, or at most remained constant, in all geographical areas. The decreasing tendency was more marked in men. Larynx cancer cohort effects for men were at a maximum for cohorts born around 1990, decreasing thereafter. In women, cohort effects appeared to consistently decrease. Overall rates of pleural cancer mortality increased during the period 1969-1987, and the sex ratio was stable, from 1980 onwards, at a value of about 2.4. Cohort effects showed, for pleural cancer, a general increase for all the cohorts. The increase was particularly apparent in male cohorts born after 1930. Overall mortality rates for cancer of the nasal sinuses was rather stable in both sexes from 1975 onwards. However, in the 35-64 year age group, mortality rates increase for males and decreased for females. PMID- 1497245 TI - [Analysis of the geographic distribution of mortality in Italy caused by tumors of the respiratory system]. AB - This paper describes the geographical distribution of respiratory cancers in Italy during the period 1970-87. We analysed mortality rates for cancers of the larynx, of the lung, of the paranasal sinuses, and of the pleura in the 95 Italian provinces. For all considered sites, Northern Italy showed the highest levels of mortality. Only Rome and Naples, the most urbanized provinces in the Central and Southern Italy respectively, presented mortality rates comparable to the Northern provinces, particularly in the early 1970's. The geographical distribution of mortality for all considered sites appears to be consistent between the two sexes. For lung cancer, however, the difference between the North and the rest of the country during the considered period decreased in men but steadily increased in women. PMID- 1497246 TI - [Analysis of mortality in relation to various demographic phenomena: migration and marital status]. AB - This paper analyzes the mortality of major respiratory cancers, certified in Italy in the years 1981-84, by two demographic phenomena: migration and civil status. Direct standardized rates were computed using the total population as reference; a partial analysis of mortality by all causes was also performed. Because of the industrial development in some areas of Italy, great migrations took place in the past within the country, with specific and well known geographic and time patterns. This paper mainly considers migrations towards the industrialized regions of the north-west both from the north-east, occurring between the two world wars, and from the south regions, occurring from the fifties to the seventies. Various studies have shown that cancer mortality decreases with the geographic latitude of the area studied, and that there is a protective effect associated with being born in the southern part of the country. Italian regions were grouped into five areas: north-west, north-east, north central, south-central and south. Individuals born in the same area of the last residence were defined as "stable", while "migrant" indicates that the area of birth differed from the last residence; for "internal migrant" both regions of birth and last residence are in the same area. For migrants to the north-west, rates by age are reported. For larynx cancer, only mortality of males is discussed. Our study's results confirm that lung cancer mortality is always higher for migrants than it is for stables from the same birth area. Immigrants also show higher rates of lung cancer mortality than the stables in the host areas. The rate ratio of emigrants versus stables in the birth area increases towards the south. The increasing protective role of birth area with decreasing latitude is confirmed for both stables and immigrants. Subjects in the north-west who emigrated from the north-east show age-specific mortality rates higher than stables, both in host and birth areas. Immigrants from southern areas show rates equal to the stables of the host area with increasing age. Results for lung cancer mortality suggest that migrants differed from the stables in socio economic characteristics not only in the birth areas but also in the host regions. For larynx cancer, migrants and stables show similar rates. Mortality rates for internal migrants and stables decrease with latitude; the protective role of birth area in immigrants is less evident.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1497247 TI - [Incidence of respiratory tract system tumors in Italy: data from the Tumor Registry]. AB - Nine population-based cancer Registries are active in Italy, covering about one tenth of the population. Six Registries (Torino, Varese, Trieste, Genova, Parma, and Forli) are located in the North of Italy, two Registries (Firenze and Latina) in the Center and one (Ragusa) in the South. Incidence data (total number of registered cases; age-specific, age-standardized, truncated, and cumulative rates) and indices of reliability (% of cases with histological verification of diagnosis; % of cases registered only as a result of death certification; and mortality/incidence ratio) are tabulated for the period 1983-87. Respiratory tumors are classified according to the three-digit codes of the International Classification of Diseases, ninth revision: 160, nose and sinuses; 161, larynx; 162, lung; 163, pleura. Standardized incidence rates for lung cancer range between 48.8 x 10,0000 (Ragusa) and 115.3 (Trieste). All the Registries in the North and in the Center show high levels of risk; rates are reduced to half for the two southern Registries. Laryngeal tumors show a similar pattern: the highest rate is observed at Trieste (21.1), and the lowest is for Ragusa (10.1). The risk of primitive pleural cancer is very high for Trieste (6.1) and Genova (5.3), where the shipyard industry is present, and homogeneously low for the other Registries. Frequency of nasal tumor is too low to establish descriptive comparisons. As a whole, for larynx, lung, and pleura, the figures from incidence data confirm those from mortality data. PMID- 1497248 TI - [Survival in respiratory tract tumors: Italian population-based data and international comparisons]. AB - Population survival studies are usually carried out within population-based cancer registries and are useful mainly for geographical and temporal survival comparisons. Survival studies based on clinical series of patients are traditionally executed to evaluate the efficacy of a given treatment or to analyze the prognostic role of clinical factors. Subjects from a case-control study on incidence of larynx and hypopharynx cancers in Turin, for the period 1979-82, were followed-up in order to study their survival. The analysis was based on 347 cases of larynx cancer (319 males and 28 females) and 48 cases of hypopharynx cancer (47 males and 1 female). For larynx cancer, observed five years survival was 59% in males and 64% in females. Hypopharynx cancer had a worse prognosis (21%). In males suffering from larynx cancer, older age, extent of spread, birth in Northern Italy, and being unmarried proved to be statistically significant negative prognostic factors. The same variables were also predictive of survival for hypopharynx cancer. The one- and three-year relative survival for larynx cancer in Turin was higher than that reported by other cancer registries. For males, relative five-year survival figures range from 47% to 65%. Survival for hypopharynx cancer is considerably lower, five-year figures ranging from 13% to 35%. The survival study on lung cancer was based on all the incident cases recorded by the Lombardy Cancer Registry (L.C.R.) from 1976 to 1981; during this period there were 2042 cases of primary lung cancers occurred in males and 217 in females. Observed survival at one, three and five years from diagnosis was 29%, 8% and 5%, respectively. Survival decreased with increasing age; no important differences between sexes are evident. Information on tumor stage was available in 1904 cases and histotype was known in 1605. Three year survival was 17% for localized tumors, 8% for tumors with regional metastasis, and 1% for tumours with distant metastasis. Epidermoid carcinomas had a better prognosis than non-epidermoid carcinomas in the first year of follow-up, survival being 38% and 29%, respectively; among non-epidermoid carcinomas the worst prognosis was for small-cell carcinomas. Comparisons between the LCR relative survival and that reported by other cancer registries did not show important differences, five-year figures ranging from 5% to 10% in males.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1497249 TI - [Prospects and indications for the prevention of respiratory tract tumors]. AB - Respiratory cancers are suitable targets for primary prevention, since their causes are largely known and can be eliminated. Reasonable short-term objectives include the reduction of tobacco use (and alcohol abuse), the control of exposure to carcinogens in the workplace, as well as the reduction of air pollution in the general environment. The International Agency for Research on Cancer has estimated that in countries like Italy the elimination of cigarette smoking could reduce larynx cancer by 85% (if accompanied by a decrease in alcohol consumption), and lung cancer by 80% in males and 60% in females. An almost complete elimination of exposure to carcinogens in the workplace could potentially reduce lung cancer by 10%, whereas eliminating exposure to asbestos could certainly reduce pleural cancer by more than 50%. The proportion of lung cancer attributable to pollution in the general environment is unclear. Preventive measures require legislative support. Since October 1991, stores throughout Italy, in compliance with a new law, started carrying the first cigarette packages that included warnings against the hazards of smoking. Not since Law 584 of 1975, which forbids smoking in public places, has such an important legislative measure been passed. As a consequence of Law 584, smoking in many public places (e.g. movie theaters and, more recently, domestic flights) is today unthinkable, and these restrictions have been widely integrated into the Italian way of life. In developed countries, there is no doubt that the reduction of cancer due to the elimination of tobacco would be greater than that due to eliminating exposure to risk factors in the workplace.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1497250 TI - [Incidence and prevalence of respiratory tumors in Italy. Estimation from mortality data]. AB - This study estimates the incidence and prevalence of larynx and lung cancers using a mathematical model based on available data on specific mortality and survival. In Italy, larynx and lung cancers account for more than 95% of respiratory cancers. In this paper, estimates of age/sex-specific and age standardized incidence rates and prevalence are presented for the years 1970 and 1987. Age and birth-cohort effects on incidence are also presented by sex and broad geographical area. The procedure was firstly validated using data from four cancer registries: Varese (Northern Italy), Parma (North-Central Italy), Florence (Central Italy), and Ragusa (Southern Italy). Estimates were then carried out at the national level and for each major geographical area (i.e. North, Center and South). Larynx cancer age-standardized incidence rates increased for men by about 25% from 1970 to 1987. Age-specific rates increased for ages greater than 44 years, but decreased for younger ages. Cohort effects are low for older cohorts; they steeply increase and plateau for the 1900-1905 cohorts, and then peak for the 1930 cohort. The risk for cohorts born after 1930 systematically decreases. We estimated that the 1930 birth cohort has a risk five times higher than the 1890 cohort. For women, the incidence rates increased by about 30% from 1970 to 1987, for all age classes. Cohort effects steadily increase from the 1886 birth cohort to the 1960 cohort. The estimated prevalence between ages 30 and 84 increased from about 24,400 cases in 1970 (23,000 males and 1,400 females) to about 51,400 cases in 1987 (48,600 males and 2,800 females). For men, 42% of the increase can be attributed to an increase in the incidence of the disease; 45% can be attributed to population aging, and only 13% to an increase in the survival probability. Corresponding figures for women are 42%, 48%, and 10%. For lung cancer, we estimated 32,000 incident cases for 1987 (28,000 men and 4,000 women), two times the corresponding figures for 1970 (14,000 men and 2,000 women). Looking at age-adjusted rates, the overall risk of lung cancer increased by about 60% for men and 52% for women during a period of 17 years. Age-specific incidence rates increased proportionally with age for ages greater than 50 years. By contrast, there was a slight but systematic risk reduction in younger age classes.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1497251 TI - Transnationalism: a new analytic framework for understanding migration. PMID- 1497252 TI - Transnationalism in the construct of Haitian migrants' racial categories of identity in New York City. PMID- 1497253 TI - Gender, class, and migration in the Dominican Republic: women's experiences in a transnational community. PMID- 1497254 TI - A review of event-related potential components discovered in the context of studying P3. PMID- 1497255 TI - Hippocampal function and schizophrenia. Experimental psychological evidence. PMID- 1497256 TI - Cognitive alterations as markers of vulnerability to schizophrenia. PMID- 1497257 TI - The modality shift effect. Further explorations at the crossroads. PMID- 1497258 TI - The pupillary response in cognitive psychophysiology and schizophrenia. PMID- 1497259 TI - P300 findings for depressive and anxiety disorders. PMID- 1497260 TI - Pharmacologic challenge in ERP research. PMID- 1497261 TI - Event-related potentials and factor Z-score descriptors of P3 in psychiatric patients. PMID- 1497262 TI - Connections: a search for bridges between behavior and the nervous system. PMID- 1497263 TI - Event-related potential investigations of cognitive development and aging. AB - Comparison of the results of the studies of cognitive development and normal aging suggests a large degree of commonality in both behavioral and ERP effects across a wide age range. Whether measured in young children, adolescents, young, middle-aged or elderly adults, the size of the ERP repetition effect did not differ among the various age groups. This was true whether memory was tested directly during continuous recognition or indirectly during variants of semantic categorization tasks. Similarly, in the studies of adult aging, the degree of RT facilitation during the semantic task did not differ with age and, in both the studies of cognitive development and aging, the degree of RT prolongation during the explicit tasks did not appear to differ as a function of age. Moreover, in the studies of adult aging, the effects of three versus two exposures of a word assessed in the PM session (TABLE 1), modulated RT similarly in all three age groups. These data argue for continuity of information processing across a very wide age range during both direct and indirect memory tasks, when retention is assessed during the recognition (for explicit testing) and repetition (for implicit testing) phases of the task. Since ERP and RT modulation do not appear to differ with age during the retrieval phases of these experiments, how can the performance differential seen in young children and older adults be explained? Some evidence comes from the ERP data recorded during the study phases of our explicit tasks. During continuous recognition, both young children and elderly adults did not show the typical subsequent "memory effect." In the case of the children, the subsequently unrecognized ERP was larger than the subsequently recognized ERP, whereas for the older adults, there was no difference between these two ERPs. Moreover, during these same tasks, the young children did show the "crossover" (new greater than old) pattern for slow wave activity, whereas the older adults did not. Since these ERP findings were obtained during the acquisition phase (i.e., to new items that had to be encoded for subsequent retrieval), the data argue for encoding difficulties as one means of explaining the performance differences seen at the two ends of the age spectrum. However, since the older adults displayed a different new/old pattern for slow wave activity, the two age groups may differ qualitatively in the strategies employed to encode items for subsequent retrieval.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1497265 TI - Selected problems of analysis and interpretation of the effects of sleep deprivation on temperature and performance rhythms. AB - One of the major methodological-analytic problems encountered by researchers in sleep deprivation involves the examination and analysis of the relationship between sleep loss and rhythmic influences on performance. The comparison of performance rhythms with physiological rhythms, e.g., body temperature, generated under the same conditions of sleep deprivation, has become an important means of testing for an endogenous source of the rhythmicity in the data and for clarifying the nature of the proposed oscillator system. Should the data sets be correlated before or after their separation into monotonic and rhythmic parts? Correlating the raw data without separating them into their components can yield negative results, while, in reality, some of the major underlying rhythms may be highly related. The example used in this chapter showed strong cross correlations of the circadian components of temperature and two performance tasks. Sleep deprivation is thus seen to interact with performance rhythms. This interaction is only revealed after the data are analyzed and broken into their component parts. This procedure leads to the conclusion that certain performance rhythms and temperature may share the same generating oscillators. PMID- 1497264 TI - Attention and para-attentional processing. Event-related brain potentials as tests of a model. AB - In 1972 when we began to analyze the vast amount of material from the laboratories of physiological psychologists, we had only a vague conceptualization of what a model of attention might look like. We began where everyone else had, with the view that everything had something to do with "arousal" but with Lacey's (1967) warning in mind that all of the dependent variables might not actually be measuring aspects of the same process. With this warning in mind, we were forced by the data to organize them into a three-systems mode. Since the first publication of this model in 1975, we have found increasing amounts of evidence to support and extend it. This evidence is briefly reviewed in the present paper in terms of the techniques employed in various types of investigation. Further, the current review of data has made it possible to specify the para-attentional substrate (the extrinsic lemniscal primary projection systems) upon which the three systems described in the earlier model operate. The earlier model was based on psychophysiological, neurobehavioral and neurochemical analyses while the current specification results from the results of recordings of event-related brain electrical responses. The conclusions derived from these results can be summarized as follows: First. It has become possible to distinguish controlled attention from the para-attentional pre- and post-attentive automatic processes upon which controls operate. Second. The pre- and post-attentive processes appear to be coordinate with activity in the extrinsic lemniscal primary sensory projection systems. Processing in these systems is reflected in the early components of event-related brain electrical potentials. These extrinsic systems are, however, not just throughputs for further processing. Rather, they are sensitive to the history of reinforcement which the subject has experienced. The concept of a limited channel capacity must, therefore, be modified to encompass this ability of organisms to improve, through practice, their competence to process a great deal of information in parallel. Competence, not capacity, limits central processing span. Third. A set of intrinsic extralemniscal processing systems has been identified to operate via a tecto-tegmental pathway to the reticular nucleus of the thalamus. The later components (N2P3, etc.) of event-related potentials have been shown to reflect processing in these systems and those that control them. Activity in these systems has been related to targeted conscious awareness.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1497266 TI - Electrophysiologic investigation of lower cranial nerve diseases by means of magnetically stimulated neuromyography of the larynx. AB - Zoom endoscopic electromyography of the larynx, as introduced in 1979, has contributed greatly to the diagnosis of lower cranial nerve palsies, but in the early stage of a vagus nerve disorder one cannot investigate the nerve conduction from the brain stem to the laryngeal muscles with electrical stimulation. As with the early diagnosis of facial nerve palsies, up to now the intracranial part of the motoric brain nerves could not be stimulated directly. With a new magnetic coil device (Novametrix, Magstim 200) this intracranial stimulation is easily possible in the awake patient with painless magnetic stimuli that induce a muscle action potential into the laryngeal muscles. Hence, an immediate diagnosis is possible. Two coils with mean diameters of 8.5 or 3 cm were used. The stimulator delivered current pulses of peak amplitude up to 5,000 A with rise times of 140 microseconds and 65 microseconds, respectively, that generated peak fields of up to 2 T. In a healthy population, cisternal stimulation of the vagus nerve leads to a muscular response in the vocal muscle after 4 to 6.6 milliseconds (mean 5 milliseconds). Cortical stimulation leads to such a response after 9.5 to 12 milliseconds. Potentials in healthy individuals have been shown to be very uniform. Stimulation in recurrent nerve palsies may show prolongation of these latencies up to 30 milliseconds. The method is limited by the fact that complete neural blocks cannot be overcome by proximal stimulation. We have applied magnetic stimulation to 190 patients with different disorders of the vagus nerve.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1497267 TI - Does intervention improve the natural course of glomus tumors? A series of 108 patients seen in a 32-year period. AB - To acquire more insight into the results of treatment versus the "natural" course of glomus tumors, we studied the clinical data of 108 patients, in 58 of whom the disease was hereditary. During a period of 32 years (1956 to 1988), 175 tumors were diagnosed: 52 glomus jugulotympanic tumors, 32 vagal body tumors, and 91 carotid body tumors. The results of radical surgical treatment were disappointing for tumors located at the skull base, ie, nonradical in 59% (n = 23) of the cases, but very good for the carotid body tumors, for which 96% (n = 68) radical excision was achieved. Moreover, surgery at the level of the skull base dramatically increased morbidity, since it frequently induced cranial nerve palsy. During the follow-up period (maximal observation time 32 years, mean 13.5 years) none of the patients died of residual or recurrent tumor or developed distant metastases, irrespective of the mode and outcome of treatment. When these results are combined with the results of pedigree analysis, a realistic approximation of the "natural" course of the disease for both hereditary and nonfamilial tumors can be made. The results raise the question of whether this natural behavior is really improved by intervention. We conclude that removal of carotid body tumors and solitary vagal body tumors should be considered in order to prevent future morbidity. However, for skull base and bilateral glomus tumors a more conservative monitored "wait and see" policy can be sensible and should be considered in any proposal for treatment of head and neck paragangliomas.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1497268 TI - Off-vertical axis rotation: a test of the otolith-ocular reflex. AB - The vestibulo-ocular reflex was studied via off-vertical axis rotation (OVAR) in the dark. The axis of the turntable could be tilted from vertical by up to 30 degrees. Eye movements were measured with electro-oculography. Results from healthy asymptomatic subjects indicated that 1) a reliable otolith-induced response could be obtained during constant velocity OVAR using a velocity of 60 degrees/s with a tilt of 30 degrees; 2) constant velocity OVAR rotation was nausea-producing and, especially if subjects were rotated in the dark about an earth-vertical axis prior to being tilted, disorienting; and 3) sinusoidal OVAR produced minimal nausea; the eye movement response appeared to be the result of a combination of semicircular canal and otolith components. We conclude that OVAR has the potential of becoming a useful method for clinically assessing both the otolith-ocular reflex and semicircular canal-otolith interaction. PMID- 1497269 TI - Stenting for pediatric laryngotracheal stenosis. AB - The treatment of pediatric laryngotracheal stenosis using open surgery to expand the airway has become a widely accepted and effective method. Stents and cartilage grafts represent the main features of expansion laryngotracheal surgery, which is indicated after failure of endoscopic treatment and/or in the presence of severe stenosis. Stenting is needed in all situations with the exception of using a single cartilage graft in the anterior subglottic lumen. There are several options available for stenting. The most valuable and commonly used stents are the Aboulker stent and the Silastic sheet roll. In looking for the features of an ideal stent, I analyzed 51 procedures using the Aboulker stent on 48 patients. The purpose of this report is to discuss these features and relate them to the Aboulker stent. PMID- 1497270 TI - Pediatric airway reconstruction at Great Ormond Street: a ten-year review. III. Decannulation and suprastomal collapse. AB - One hundred eight consecutive patients with pediatric laryngotracheal stenosis requiring airway reconstruction over a 10-year period were reviewed. Ninety (83%) of the patients were decannulated. Over three quarters of the decannulations took place within 20 months of primary reconstruction. More than half of the patients (47, or 52%) had persistent tracheocutaneous fistulae after decannulation, which required elective closure. The likelihood of a persisting tracheocutaneous fistula is directly related to duration of cannulation. PMID- 1497271 TI - Comparison of speech recognition ability with different speech processing strategies by Korean cochlear implantees. AB - Many variables affect the audiologic performance of cochlear implantees. With current methods of evaluation, it is difficult to directly compare auditory function with different speech coding strategies. We compared the audiologic performance directly with F0F1F2 and multipeak speech coding strategies in the same implanted ear of eight Korean cochlear implantees. We tested word and phoneme recognition abilities using Korean word lists for speech audiometry and two-syllable nonsense words, respectively. With the multipeak coding strategy, a significant difference in discrimination ability was found in the initial fricative consonant phonemes (/s/,/ss/,/h/). Our results suggest that the improvement of speech recognition ability with the multipeak coding strategy comes primarily from the better understanding of the initial fricative consonants. PMID- 1497272 TI - Solitary plasmacytoma of the skull base. AB - Plasmacytomas involving the skull base are rare lesions that may be well advanced by the time of diagnosis. Because of their anatomic site they may produce a variety of signs and symptoms, some of which may be vague, often resulting in delays in presentation and in appropriate investigations. We present such a patient, discuss the diagnosis and management, and give a review of the literature. PMID- 1497273 TI - Macroporous biphasic calcium phosphate efficiency in mastoid cavity obliteration: experimental and clinical findings. AB - Following our previous experimental studies on the performance of macroporous biphasic calcium phosphate (MBCP) in canine mastoid cavities, we used this material in patients requiring surgical intervention. Twenty-two cases were selected, and in eight specific cases a biopsy specimen was taken. Histologic, ultrastructural, and microanalysis studies were performed. This study demonstrates the effectiveness of MBCP implants as bone graft substitutes for mastoid cavity obliteration. Clinical evaluation of the series and histologic and ultrastructural results demonstrated the bioactivity and osteo-conduction of this material, with partial transformation of MBCP granules into lamellar bone after several months. PMID- 1497274 TI - Airflow study of pathologic larynges using a constant temperature anemometer: further experience. AB - Phonatory airflow was recorded in 361 laryngeal disease patients and 59 normal subjects by using a constant temperature anemometer to measure Isshiki's proposed parameter, the AC/DC percentage. The pathologic groups displayed AC/DC percentage values smaller than those of the normal group. The value differentials observed among the various diseases suggest that the AC/DC percentage may reflect the vibrational capacity of the vocal cords. PMID- 1497275 TI - Corneal autoimmunity in Cogan's syndrome? Report of two cases. AB - Autoimmune reactivity against corneal antigens is described in two patients with Cogan's syndrome, a nonsyphilitic deep interstitial keratitis with vestibuloauditory symptoms. In both cases corneal antibodies were found at the beginning or during an exacerbation of the disease. After administration of high doses of corticosteroids the corneal antibodies diminished. Interstitial keratitis can generally be controlled by local or systemic corticosteroids. The effect of corticosteroid therapy on the audiovestibular symptoms is variable. The possibility of an autoimmune pathogenesis of Cogan's syndrome is discussed. PMID- 1497276 TI - Giant air cell of the petrous apex: a possible cause of facial hypalgesia. AB - A giant air cell of the left petrous apex was found in a 23-year-old man with ipsilateral facial hypalgesia. The size of the giant air cell depicted on computed tomography was 1.5 x 2.0 x 2.0 cm. A coronal T1-weighted magnetic resonance image showed that the trigeminal nerve was compressed superomedially by a large signal void area that was probably a result of excessive pneumatization of the petrous apex. It is suggested that the facial hypalgesia was caused by the compression by the giant air cell of the petrous apex on the trigeminal nerve. PMID- 1497278 TI - Quantitative ultrastructural study of cat abducens interneurons. AB - Abducens interneurons project to the medial rectus subdivision of the contralateral oculomotor nucleus and have a role in the mediation of horizontal conjugate gaze. Two types of interneurons have been reported based on shape (fusiform and circular) and differences in organelles. In this study, 41 abducens interneurons from three young adult cats were examined in the transmission electron microscope and were classified, on the basis of eccentricity (e), as circular (e less than 0.82; N = 18) or fusiform (e greater than or equal to 0.82; N = 23). The volume fraction of nucleus, nucleolus, mitochondria, rough endoplasmic reticulum, polyribosomes, and Golgi complex and the number of synaptic profiles per 100 microns of membrane were determined. Although there is a qualitative difference in these cell types, statistical analyses indicate no significant differences in organelle content, mean area, number of synaptic profiles per 100 microns of membrane, or diameter. While the differences in shape may possibly indicate different functional groups, this notion is not supported by the variables examined or by physiological studies. PMID- 1497277 TI - Bovine temporal bones as a source of inner ear antigen. AB - Modern immunologic techniques of immunostaining, immunoblotting, and creation of monoclonal antibodies are gaining wide application in studies of development, function, and pathology of the ear. These techniques require a source of inner ear tissue for production of antigen extract. Human tissue is not readily available, and other mammalian species common in auditory research are small in size. Bovine temporal bones are readily available, and the membranous portions of the inner ear are abundant and easily accessible. Herein we report our technique for acquisition and dissection of bovine temporal bones and preparation and preservation of inner ear antigen. PMID- 1497279 TI - Anatomy of the guinea pig temporal bone. AB - The middle ear of guinea pigs has long been used for experimental studies, but no detailed information about its temporal bone anatomy is available. In 18 adult guinea pigs, the temporal bone, eustachian tube, and inner ear anatomy, in addition to the anatomy of the middle ear, were investigated under the dissection microscope. In addition to properties of the eardrum, ossicles, air cell system, and cochlea previously described, the appearance of Huschke's foramen and the crista stapedis in an adult guinea pig ear, the structure of the eustachian tube, the architecture of the internal auditory canal, and the communication of the mastoid cells with the tympanic bulla are described. Differences and similarities among guinea pigs, other experimental animals, and humans are discussed to show the advantages and disadvantages of the guinea pig ear for experimentation. PMID- 1497280 TI - Aneurysm of the anterior inferior cerebellar artery producing hearing loss. PMID- 1497281 TI - Bone scan diagnosis of masked mastoiditis. PMID- 1497282 TI - [Drug therapies in anxiety disorders of children]. AB - Although childhood anxiety disorders are currently generating new interest, they continue to pose problems in everyday clinical practice. Drug treatment is far from being the only therapeutic approach but does undeniably have a place which should be clearly defined. The main drugs, dosages, indications, and adverse effects of antidepressants, benzodiazepines, antihistamines and neuroleptics which may be used in children with anxiety disorders are discussed. PMID- 1497283 TI - [Recurrent bronchopneumopathies in the infant due to swallowing dyspraxia. Two cases]. AB - In two infants with recurrent lower respiratory tract infections starting within a few weeks of birth, dynamic electromyographic studies of sucking and swallowing evidenced a disorder of lingual and pharyngeal activities responsible for the episodes of aspiration. The central location of the anomaly was demonstrated by the absence of peripheral neuromuscular anomalies and by the presence of impaired blinking reflexes and brain stem potential anomalies. These neurofunctional anomalies improved over time and magnetic resonance imaging failed to disclose and structural anomalies of the central nervous system. The occurrence of the swallowing disorder as an isolated manifestation and its long duration, with follow-ups of 23 months and 4 years, are two unique features in these cases. Neurophysiologic investigations are essential for documenting the neurologic etiology of the swallowing disorders, demonstrating their location above or within the medulla oblongata, and differentiating functional and organic anomalies. PMID- 1497284 TI - [Compliance with treatment in diabetic adolescents]. AB - The study of compliance with therapy among teenagers with diabetes mellitus is a challenging task. Although several studies have addressed this problem, available knowledge in this field remains scant and the lack of understanding of factors which determine compliance with therapy hinders the development of interventions capable of helping diabetic teenagers to improve their quality of life. On the basis of a review of the relevant literature, this paper discusses compliance with therapy in the light of the specific features of teenage development. The two main theoretical models used to explain compliance with therapy in adolescent diabetics are presented. Parameters of compliance with therapy and the methods used to measure these parameters are also discussed. PMID- 1497285 TI - [Lymphoid hyperplasia of the intestine in children. 15 cases]. AB - Fifteen cases of nodular lymphoid hyperplasia (NLH) of the bowel in patients aged 17 months to 15 years are reported. Fourteen patients had NLH confined to the small bowel and one had involvement of both the small bowel and colon. Mean age at diagnosis was 10 years. The most common presenting symptoms were intestinal manifestations (86%). Diagnosis was suspected upon roentgenographic studies in one case and digestive endoscopy in ten cases. Histologic confirmation was obtained in all fifteen patients. Immunohistochemical studies, done in 8 patients, demonstrated a paucity of IgA plasmocytes in one patient with an immune deficiency and a polyclonal plasmocyte population with mainly IgA plasmocytes in the seven other patients. Five patients had a deficiency in humoral immunity, with variable expression hypogammaglobulinemia in three patients and IgA deficiency in two; intestinal giardiasis was found in eight patients. Histologic outcome was documented in five cases; evidence of NLH disappeared in only one patient. Metronidazole improved clinical symptoms in most instances. PMID- 1497286 TI - [Infantile cystinosis. A new Tunisian case]. AB - A case of cystinosis in a three and a half-year-old is reported. Suggestive manifestations included severe rickets, small stature, and complex renal tubule dysfunction meeting the criteria for secondary Fanconi syndrome. Diagnosis was established by the discovery of retinal lesions upon ophtalmologic evaluation and, above all, by the finding that intracellular leukocyte cystine levels were increased to 16 mumol of 1/2 cystine per gram protein. Cystinosis is severe because it inevitably leads to renal failure. Much hope is currently placed in the use of cysteamine to delay this and other complications. At present, early antenatal diagnosis during the first ten weeks of pregnancy is needed in high risk families to allow elective termination of pregnancy within the legal time limit. PMID- 1497287 TI - [HbD Iran-beta-thalassemia association in a Tunisian family]. AB - A nine-year-old boy from Beja (North-Western Tunisia) was found to have both HbD Iran and beta-thalassemia. This patient presented with anemia and slight enlargement of the spleen and had a history of acute episodes of hemolysis. Structural studies on this hemoglobin variant used several miniaturized techniques, mainly carboxy-methyl-cellulose chromatography, reverse-phase high performance liquid chromatography and manual peptide sequencing using Chang's technique. The glutamic acid in position 22 on the beta chain was found to be replaced by a glutamine, establishing the diagnosis of HbD Iran. Concomitant presence of a thalassemia trait was suggested by the finding in the index patient of microcytosis, hypochromia and increased HbA2. The family study confirmed this patient's combined heterozygous anomalies, showing the D trait in the father and the beta thalassemia trait in the mother. The same combination was found in the index patient's sister who was, however, free of clinical symptoms. The explanation of this difference in clinical expression was provided by the ADN study which disclosed deletion of an alpha gene in the girl. The resulting alpha chain deficiency counterbalanced the beta chain deficiency. PMID- 1497288 TI - [Posterior urethral valves in Senegalese children. Fourteen cases]. AB - Fourteen pediatric cases of posterior urethral valves in patients aged 6 months to 14 years (with four infants and ten older children) are reported. The main symptoms were vesical, including dysuria, acute urinary retention and dribbling. One patient presented with diarrhea, vomiting and dribbling. Urethral valves were looked for as part of the evaluation for urinary lithiasis in one patient, and in another urinary lithiasis developed following the diagnosis of urethral valves. In half the cases, onset of symptoms occurred within one year of birth. Urethrocystography allowed to evidence the valves and to evaluate repercussions on the bladder including hyperplasia (7 cases) and diverticula (2 cases). The intravenous urogram disclosed bilateral ureterohydronephrosis in eight cases. Pathogens recovered from the urine included Klebsiella (3 patients), Pseudomonas (4 patients), Proteus (one patient), and E. coli (one patient). Most patients were treated by catheter lamination under antimicrobial therapy. Two patients died from renal failure. Results were considered satisfactory in nine cases with follow-ups ranging from 1 month to 4 years. Three patients were lost to follow up. Early diagnosis is essential and management should rely mainly on endoscopic resection which reduces the length of the hospital stay and the risk of infection. PMID- 1497289 TI - [Incidence of peri- and intraventricular hemorrhages in a premature population at the Central Hospital of Yaounde (Cameroon)]. AB - In Cameroon, prematurity is common but few studies have been carried out on periventricular and intraventricular hemorrhage in premature neonates. Seventy neonates born between 28 and 34 weeks gestational age were studied by cerebral ultrasonography. Thirty infants (42.8%) showed evidence of periventricular or intraventricular bleeding. This proportion was 58.3% in infants born between 28 and 31 weeks gestational age. All stage III (3 cases) and stage IV (2 cases) hemorrhages were bilateral. Bilateral bleeding was less common among patients with stage I (2 cases) or stage II (2 cases) hemorrhages. Among patients born between 32 and 34 weeks gestational age, only 34.8% had ventricular hemorrhage which was always stage I or II and usually unilateral (two stage I and one stage II bilateral bleeds). The incidence of periventricular and intraventricular hemorrhage is high in Yaounde. Ultrasonographic evaluation should be routinely performed in infants born before 35 weeks gestational age. PMID- 1497290 TI - [Epidemiologic and clinical aspects of child tuberculosis in Gabon. Retrospective study of 47 cases]. AB - Forty-seven pediatric cases of tuberculosis seen over three years in a department of general pediatrics are reviewed. The main epidemiological and clinical features were studied. Yearly incidence approximated 1.42% in the department. In most instances the source of contamination was not identified. Most patients had not been immunized according to recommendations. Early immunization should be performed and followed by routine tests for vaccine-induced immunity during the first two years. PMID- 1497291 TI - [Acute diarrhea of viral origin in the infant and young child]. PMID- 1497292 TI - Membranous bone lengthening: a serial histological study. AB - Bone lengthening using the process of corticotomy and gradual distraction of callus is applicable to the membranous bone of the canine mandible. In this study the precursors to bone formation, in the area between the distracted bone edges, are analyzed in an attempt to determine the mechanism of bone formation. Ten mongrel dogs 5 months of age were studied. A unilateral, periosteal-preserving angular corticotomy was performed, and an external bone-lengthening device was fixed to the mandible. After 10 days of external fixation, the mandible was lengthened 1 ml per day for 20 days and then held in external fixation for 8 weeks. The dogs were killed for histological and microradiographic study at 10 and 20 days of distraction, and at 14, 28, and 56 days after the completion of distraction. It was observed that the gap between the distracted bone edges is first occupied by fibrous tissue. As distraction proceeds, the fibrous tissue becomes longitudinally oriented in the direction of distraction. Early bone formation advances along the fibrous tissue, starting from the cut bone ends. Eventually the area is converted to mature cortical bone. Bone is formed predominantly by intramembranous ossification. This mechanism is similar to that of bone formation during long bone lengthening. PMID- 1497293 TI - Improving the acute nasolabial angle and medial nasolabial fold by levator alae muscle resection. AB - An acute nasolabial angle and a prominent nasolabial fold are two features that are often associated in the aging face. A new technique is presented that simultaneously addresses both of these features. Levator alae (levator labii superioris alaeque nasi) muscle resection, performed through a subciliary incision, improves the acute nasolabial angle without concomitant rhinoplasty. At the same time, levator alae muscle resection softens the medial nasolabial fold. Partial levator labii superioris muscle resection has occasionally been added to further weaken the middle nasolabial fold. Fresh cadaver dissections were performed to define the anatomy and to plan the surgical approach. This report describes a series of 10 patients who underwent this procedure, with improvement of the acute nasolabial angle and softening of the medial nasolabial fold. PMID- 1497294 TI - Tissue expansion in the extremities using external reservoirs. AB - Over a 24-month period, 18 patients had 33 expanders placed in the extremities. Twelve expansions were performed in the upper extremity, and 21 in the lower extremity. Indications for expansion include scarring, excision of skin grafts, tumor excision, burn scars, tattoos, or unacceptable incisional scars for revision. Of the 12 expansions performed in the upper extremity in seven patients, nine were successful. Nine expansions in the thigh and two expansions in the region of the knee were completed without complication. Three expansions were performed in the distal lower extremity following crush injury to remove scarring, and all three failed. Seven expansions were performed in the foot for removal of scarred tissue. There was one infection, two skin necroses on the dorsum of the foot, and one implant exposure. Seven complications in the lower extremity occurred in these areas with an infection rate of 20%. The remaining 23 expansions were performed for soft tissue defects in the upper extremity or in the lower extremity above the level of the mid-calf, with only two complications of implant exposure or infection. Therefore, the infection rate and complication rate in the upper extremity and above the knee was only 6%. Overall, 23 of the 33 expansions, or 70%, were taken to completion with a successful advancement of expanded flaps. Overall, complications occurred in 30% of patients, all eventually requiring removal of the expander.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1497295 TI - Heterotopic ossification as a complication of the staged total thigh muscles flap in spinal cord injury patients. AB - Between 1980 and 1990, 24 total thigh flap procedures were performed at Rancho Los Amigos Medical Center (Downey, CA) by the Pressure Ulcer Management Service. An unexpected occurrence was identified, that is, the rapid development of heterotopic ossification (HO) occurring in the exposed muscle flap between the first and second stages. There were 15 two-stage total thigh flap procedures on 14 patients performed between 1980 and 1990. Of these 15 flap procedures, 11 in 10 patients were found to have HO evident at the second-stage debridement/closure. In comparing our findings with those in other studies (earliest evidence of HO at 19 days), the initial presentation of HO in affected tissues might be even earlier than previously detected. The risks and technical difficulties due to development of HO associated with the two-stage total thigh flap procedure point toward future modifications in preoperative planning that may prove beneficial. Therefore, if the two-stage total thigh flap procedure is necessary, the interval between initial debridement/disarticulation (stage 1) and definitive flap closure (stage 2) should be kept to an absolute minimum. Additionally, HO medicinal prophylaxis (that is, indomethacin or diphosphonates) or radiation after the first stage of the total thigh flap procedure should be considered. Our final conclusion is that the total thigh flap procedure should be done as a one-stage procedure if possible. PMID- 1497296 TI - The universal nose of early childhood: nature's aid in understanding the supratip deformity and its correction. AB - The noses of the babies of the world are strikingly similar despite race. Overresected noses have the same characteristics as babies' noses for exactly the same reason: in both cases the nasal skin is relatively unsupported by its underlying skeleton. Teaching rhinoplasty is a most difficult task, but nature offers valuable help in understanding the delicate balance between nasal skeleton and skin sleeve. Nature transforms the "universal nose of early childhood" into an adult nose by gradually augmenting the nasal skeleton, thus showing us the way to correct the iatrogenically overreduced nose. PMID- 1497298 TI - The influence of diabetes on free flap transfer: II. The effect of ischemia on flap survival. AB - Insulin-dependent diabetes mellitus causes microangiopathic changes in many tissues, including skin and muscle. It is not known if such changes are detrimental to free flap transfer, particularly after extended ischemia. To address this issue, we used an experimental design by using a syngeneic rat strain (Lewis) for free groin flap and muscle flap transplantations from streptozotocin-induced diabetic rats (2 month's duration of symptoms) to normal rats. Flaps from age-matched normal donors were transplanted to normal recipients for control comparisons. Groin flaps were stored ischemically for 12 or 18 hours at room temperature, or for 48 hours in the cold (4 degrees C) before transplantation. Flap survival and vascular patency were assessed at 7 days. Cutaneous maximus muscle flaps were transplanted to the groins of recipients after 6 hours of room temperature ischemia. Vascular patency, muscle viability, flap weight change (edema), and dehydrogenase activity were assessed after 2 days of reperfusion. Seventy percent, 67%, and 73% of diabetic groin flaps survived after 12, 18, or 48 (cold) hours of ischemia, respectively, in comparison with 90%, 73%, and 87% of normal flaps undergoing the same respective ischemia periods. The differences were not significant, even when the data were pooled (p greater than 0.1). Muscle flaps also showed no significant differences for the parameters studied. These results support the use of microvascular reconstructive surgery in diabetic patients, suggesting that moderate ischemic challenges do not compromise free flap transfer or extremity replantation. PMID- 1497297 TI - The influence of diabetes on free flap transfer: I. Flap survival and microvascular healing. AB - Although recent clinical case presentations suggest that diabetes does not predispose free tissue transfers to increased risk of failure, this remains an open question. The present study used a syngeneic rat strain (Lewis) for free groin flap transplantations between normal rats and streptozotocin-induced diabetic rats (2 months' duration of symptoms), to investigate the influence of diabetes on flap transfer. Flap survival at 1 week, vascular patency, flap histology and ultrastructure, and scanning electron microscopy of anastomotic sites and of corrosion casts of flap vasculature were used as bases for comparison. No differences were found in comparisons of flap survival between any groups of transfer combinations (normal flap onto normal recipient, diabetic flap onto normal recipient, normal flap onto diabetic recipient, and diabetic flap onto diabetic recipient); 100% success was achieved in each group. No differences were found in histology or corrosion casts. Transmission electron microscopy revealed a thickening of the capillary basement membrane in rat diabetic skin after only 8 weeks of symptoms. This ultrastructural finding is consistent with similar capillary basement membrane thickening seen in many other tissues of short- and long-term diabetic animals and humans. Re-endothelialization across the arterial anastomosis at 2 weeks postoperatively was significantly faster in normal versus diabetic animals (p less than 0.05). The predominantly negative findings of this study support the application of free flap transfers in diabetic patients. It is concluded that reconstructive efforts involving free tissue transfer may not be contraindicated in diabetic patients. PMID- 1497300 TI - Reconstruction of the distal foot dorsum with a distally based extensor digitorum brevis muscle flap. AB - We have successfully applied a reverse flow island flap of extensor digitorum brevis muscle for coverage of tissue defects in the distal portion of the foot dorsum in 2 patients. This flap covered the metatarsophalangeal area well with cadaver limb dissection and seems useful to cover the defect in the distal foot dorsum. PMID- 1497299 TI - Clinical application of the adipofascial turnover flap in the leg and ankle. AB - In soft-tissue defects with bone exposure over the leg and ankle, it is often impossible to achieve wound closure by a simple skin graft. In this article, we present a simple and effective way to reconstruct complicated skin defects on the pretibial region (four patients), the ankle (three patients), the distal fibula (one patient), and the medial aspect of the leg (one patient). Dissection of the local adipofascial turnover flap is quite easy and quick, requires less time, and involves less risk to the patient. It can be completed as a single-stage procedure, and no muscle function or major artery must be expended. Although there are numerous options for reconstruction of soft-tissue defects of the leg and ankle, the nonbulky adipofascial turnover flap appears particularly indicated for small- to medium-sized defects. The contours of the recipient and donor sites are acceptable aesthetically. Adequate flap-to-base area ratio and length-to width ratio, tension-free insetting of the flap, and noncompression dressing are essential for the flap's survival. PMID- 1497301 TI - Verification of the pressure provocative test in carpal tunnel syndrome. AB - Three provocative tests (pressure, Phalen's test, and Tinel's sign) were studied in 30 patients with carpal tunnel syndrome and 30 control subjects. The pressure provocative test had a sensitivity of 100%. In contrast, Phalen's test was 88% sensitive and Tinel's sign only 67% sensitive. The pressure provocative test is a sensitive indicator of median nerve compression at the wrist with a faster reaction time than Phalen's test (mean time of 9 seconds vs 30 seconds). It is an appropriate provocative test in patients with stiff or painful wrists when wrist flexion is restricted. PMID- 1497302 TI - Transinterosseous transfer of a peroneal island flap for reconstruction of prepatellar skin defect: report of two patients. AB - We describe the use of a peroneal vascular transinterosseous island flap for the resurfacing of a prepatellar skin defect in 2 patients. Being a fasciocutaneous flap, the peroneal flap is thin, and the location of perforators is easily and safely detected with a Doppler flowmeter. When used as a vascular island flap, either a distal pedicle or a proximal pedicle can be used. The peroneal flap can be used as either a free flap or a vascularized fibular and fasciocutaneous flap. It may, therefore, be applied to compound skin, subcutaneous tissue, and bone defects in the lower extremities. A peroneal vascular transinterosseous island flap can reach a prepatellar skin defect, whereas the peroneal island flap with conventional proximal pedicle cannot. PMID- 1497303 TI - Massive extravasation of traumatically ruptured buttock silicone prosthesis. AB - Although requests for gluteal implants are unusual in the United States, the use of silicone implants for buttock cosmesis has been described. Complications of this procedure have rarely been reported. There are no reports of long-term follow-up in these patients. This report describes the traumatic rupture of a silicone buttock implant nine years after initial surgical placement. Massive silicone extravasation and migration, along with silicone granuloma formation, occurred. The contralateral implant remained intact, functional, and cosmetically acceptable. The surgical approach and repair of this injury is outlined and discussed. We conclude that early surgical treatment of extravasation injuries is needed and that buttock reconstruction with implants can be useful, but close follow-up is needed. We also suggest there is a need to evaluate alternative materials for use in this procedure. PMID- 1497304 TI - Congenital alveolar adhesions. AB - We report an infant girl with congenital alveolar adhesions and a cleft palate. The mucosal bands were resected the day after birth. Stretching exercises of the mandible improved the range of movement at the temporomandibular joint. Two weeks of therapy were required before full mouth opening was possible. Previously reported patients and theories of embryogenesis are reviewed. PMID- 1497305 TI - Sailing to Byzantium. PMID- 1497306 TI - Transcription factors: structural families and principles of DNA recognition. PMID- 1497307 TI - Telomerases. PMID- 1497308 TI - Diseases of the mitochondrial DNA. PMID- 1497309 TI - Differentiation requires continuous active control. AB - The problems posed by differentiation that appear most soluble by a passive control mechanism can readily be solved by an active mechanism. Given the need for plasticity in gene expression in different cell types at different stages, an active mechanism may be advantageous, even essential. It is striking how few changes during differentiation are completely irreversible, the gene rearrangements leading to immunoglobulin expression being one clear exception. Indeed, a prediction of the active-control hypothesis is that any nucleus exposed to the appropriate constellation of proteins at the appropriate concentration should be able to perform functions typical of any given differentiated cell type. In the next decade, the elucidation of novel memory mechanisms, or feedback loops, will substantially increase our understanding of how stable differentiated states can be maintained by continuous active control. PMID- 1497310 TI - DNA looping. AB - DNA looping is widely used in nature. It is well documented in the regulation of prokaryotic and eukaryotic gene expression, DNA replication, and site-specific DNA recombination. Undoubtedly looping also functions in other protein-DNA transactions such as repair and chromosome segregation. While the underlying physical chemistry of DNA looping is common to all systems, the precise biochemical details of looping and the utilization of looping by different systems varies widely. Looping appears to have been chosen by nature in such a wide variety of contexts because it solves problems both of binding and of geometry. The cooperativity inherent in binding a protein to multiple sites on DNA facilitates high occupancy of DNA sites by low concentrations of proteins. DNA looping permits a sizeable number of DNA-binding proteins to interact with one of their number, for example RNA polymerase. Finally, DNA looping may simplify evolution by not requiring a precise spacing between a protein's binding site and a second site on the DNA. PMID- 1497311 TI - Mammalian DNA ligases. PMID- 1497312 TI - Chromosome and plasmid partition in Escherichia coli. PMID- 1497313 TI - Catalytic antibodies. PMID- 1497314 TI - Recombinant toxins as novel therapeutic agents. PMID- 1497315 TI - Protein isoprenylation and methylation at carboxyl-terminal cysteine residues. PMID- 1497316 TI - Constrained peptides: models of bioactive peptides and protein substructures. PMID- 1497317 TI - Animal cell cycles and their control. PMID- 1497318 TI - Vesicle-mediated protein sorting. PMID- 1497319 TI - N-(carboxyalkyl)amino acids: occurrence, synthesis, and functions. PMID- 1497320 TI - Enzymes and molecular mechanisms of genetic recombination. PMID- 1497321 TI - Small catalytic RNAs. PMID- 1497322 TI - Prokaryotic DNA replication. PMID- 1497323 TI - Control of nonmuscle myosins by phosphorylation. PMID- 1497324 TI - myc function and regulation. PMID- 1497325 TI - Biochemical insights derived from insect diversity. PMID- 1497326 TI - Zinc proteins: enzymes, storage proteins, transcription factors, and replication proteins. AB - In the past five years there has been a great expansion in our knowledge of the role of zinc in the structure and function of proteins. Not only is zinc required for essential catalytic functions in enzymes (more than 300 are known at present), but also it stabilizes and even induces the folding of protein subdomains. The latter functions have been most dramatically illustrated by the discovery of the essential role of zinc in the folding of the DNA-binding domains of eukaryotic transcription factors, including the zinc finger transcription factors, the large family of hormone receptor proteins, and the zinc cluster transcription factors from yeasts. Similar functions are highly probable for the zinc found in the RNA polymerases and the zinc-containing accessory proteins involved in nucleic acid replication. The rapid increase in the number and nature of the proteins in which zinc functions is not unexpected since zinc is the second most abundant trace metal found in eukaryotic organisms, second only to iron. If one subtracts the amount of iron found in hemoglobin, zinc becomes the most abundant trace metal found in the human body. PMID- 1497327 TI - Amyloidosis. PMID- 1497328 TI - Mass spectrometry of peptides and proteins. PMID- 1497329 TI - The value of electrophoretic fingerprinting and karyotyping in wine yeast breeding programmes. AB - Electrophoretic banding patterns of total soluble cell proteins, DNA restriction fragments and chromosomal DNA were used to characterise ten strains of Saccharomyces cerevisiae used for commercial production of wine. These fingerprinting procedures provided unique profiles for all the different yeast strains and can therefore be used to identify and control industrial strains. Furthermore, the protein profiles, restriction fragments banding patterns and electrophoretic karyotyping by contour clamped homogeneous electric field electrophoresis (CHEF), were valuable to differentiate hybrid and parental strains in yeast breeding programmes. Hybrid strains, with desirable oenological properties, were obtained by mass spore-cell mating between a heterothallic killer yeast and two homothallic sensitive strains and all were shown to have unique DNA fingerprints and electrophoretic karyotypes. PMID- 1497331 TI - The occurrence of disporous Bacillus thuringiensis cells. AB - Ultrathin sections of sporulating Bacillus thuringiensis were examined in a transmission electron microscope. Less than 1% of the about 2,000 approximately sagittal sections of the bacterial cells examined contained two endospores per cell. This finding clarifies the majority of textbook and research reports (which tend to be ambiguous), contradicts several of the most recent textbook reports, and confirms three unillustrated textbook reports, in relation to the occurrence of disporous bacilli. Electron microscopic evidence of the observation is presented, apparently for the first time. PMID- 1497330 TI - Arginine and proline genes of Aspergillus niger. AB - Aspergillus niger mutants defective in arginine or proline biosynthesis have been isolated and 12 genetic loci were identified. Mutation was induced by low doses UV, and mutants were isolated after filtration enrichment. The mutants were classified according to their phenotype in growth tests and were further characterized in complementation tests. The arginine auxotrophic mutants represent nine complementation groups. Three additional complementation groups were found for mutants that could grow on proline (two of them on arginine too). Linkage group analysis was done in somatic diploids obtained from a mutant and a master strain with genetic markers on six chromosomes. The arg genes belong to six different linkage groups and the pro genes to two. One arg-mutant could be complemented by transformation with the A. nidulans argB+ gene, and this A. niger gene thus appeared to be homologous to the A. nidulans argB. We isolated an A. niger strain with the argB gene tightly linked with the nicA1 marker. This strain is very suitable as acceptor for transformation with an argB-plasmid, because transformants with inserts on the homologous site can be recognized and analyzed genetically using the nicA1 marker gene. PMID- 1497332 TI - Botryozyma nematodophila gen. nov., spec. nov. (Candidaceae). AB - The new genus Botryozyma with a single species, B. nematodophila is proposed for two isolates from nematodes (Panagrellus zymosiphilus) occurring in grapes with sour-rot. The new genus has typical ascomycetous characteristics and, being unable to produce ascospores, is placed in the family Candidaceae. PMID- 1497333 TI - Neotypification of the genus Trichosporon. AB - The currently accepted type species of the genus Trichosporon Behrend is T. beigelii. This species has formerly been regarded as identical to T. cutaneum. However, these fungi are now known to represent separate species with different ecology. The first species described in Trichosporon was T. ovoides, an agent of human white piedra. A neotype strain is designated for this species, while a lectotype strain is indicated for T. cutaneum. The name T. beigelii is considered as doubtful and consequently cannot be maintained. PMID- 1497335 TI - The flocculation of wine yeasts: biochemical and morphological characteristics in Zygosaccharomyces--flocculation in Zygosaccharomyces. AB - The floc-forming ability of flocculent strains of Zygosaccharomyces bailii and Z. fermentati, isolated from musts, was tested for susceptibility to proteinase and sugar treatments. Z. fermentati was found highly resistant to the proteolytic enzymes tested, whereas Z. baili was only trypsin-resistant. The inhibition of flocculation by sugars distinguished two types: in Z. fermentati flocculation was completely inhibited by mannose, in Z. bailli by various sugars. By SEM observation, the cell surface of Zygosaccharomyces revealed the presence of a column structure, resulting from fusion of vesicles present on the cell surface. PMID- 1497334 TI - Contributions to a revision of the genus Trichosporon. AB - The genus Trichosporon was revised using characters of morphology, ultrastructure, physiology, ubiquinone systems, mol% G + C of DNA, DNA/DNA reassociations and 26S ribosomal RNA partial sequences. A total of 101 strains was used, including all available type and authentic cultures of previously described taxa. Nineteen taxa could be distinguished, 15 of which having Q-9 coenzyme systems and 4 having Q-10. Sixteen previously described names were reduced to synonymy. One new species was described. The genus is characterized by the presence of arthroconidia. Few species possess further diagnostic morphological characters, such as the presence of appressoria, macroconidia or meristematic conidiation. The septa of two species were found to be non perforate, while those of the remaining species contained dolipores at variable degrees of differentiation, with or without vesicular or tubular parenthesomes. All species were able to assimilate a large number of carbon compounds; visible CO2 production was absent. The genus was found to be fairly homogeneous on the basis of a phylogenetic analysis of partial 26S rRNA sequences, with the exception of T. pullulans which proved to be unrelated. Most taxa were found to occupy well-defined ecological niches. Within the group of taxa isolated from humans, a distinction could be made between those involved in systemic mycoses and those which mainly caused pubic or non-pubic white piedras, respectively. One species was consistently associated with animals, while others came mainly from soil or water. One species was mesophilic and another psychrophilic. PMID- 1497336 TI - Detection of Aspergillus and Penicillium extracellular polysaccharides (EPS) by ELISA: using antibodies raised against acid hydrolysed EPS. AB - Species of the fungal genera Aspergillus and Penicillium produce immunologically active extracellular polysaccharides (EPS) in which galactofuranose residues are immunodominant. The antigenic determinant of the EPS of A. fumigatus, A. niger and P. digitatum could be removed by acid hydrolysis. Due to the hydrolysis of the EPS the immunological reaction between IgG anti-native EPS and hydrolysed EPS disappeared. Antibodies raised in rabbits against the acid hydrolysed EPS revealed new antigenic determinants that were exposed as a result of the acid hydrolysis. Immunological inhibitory experiments showed that the antibodies were no longer directed to galactofuranose residues. Enzyme Linked Immunosorbent Assay, carried out with antibodies raised against the acid hydrolysed EPS showed that the antibodies against the acid hydrolysed EPS were more species specific in comparison with the antibodies against the native EPS. PMID- 1497337 TI - Plasmid-determined resistance to arsenic and antimony in Pseudomonas aeruginosa. AB - Resistance to arsenic salts in a Pseudomonas aeruginosa clinical isolate was shown to be determined by a 100 kb transferable plasmid. The resistance pattern included arsenate, arsenite, and antimonate ions. Arsenate and arsenite resistances were inducible by previous exposure of cultures to subinhibitory amounts of either of the two ions. Phosphate ions protected P. aeruginosa cells from the toxic effects of arsenate but did not alter arsenite toxicity. PMID- 1497338 TI - The role of an endogenous nonheme iron in microsomal redox reactions. AB - Microsomal membranes contain a nonheme iron which serves in vitro for the peroxidation of unsaturated lipids or the oxidation of several other chemicals. These redox reactions are reviewed in light of a recent identification of two or more iron-binding proteins in the microsomal milieu. Indirect evidence that the microsomal iron might serve in vivo for the synthesis of heme iron is also presented and discussed. Consistent with this, the newly identified iron proteins not only participate in redox reactions but also release their bound iron upon incubation with certain intermediates of heme synthesis. PMID- 1497339 TI - Allosteric regulation of tPA-mediated plasminogen activation by a modifier mechanism: evidence for a binding site for plasminogen on the tPA A-chain. AB - We studied the mechanism responsible for nonlinear double reciprocal plots for tissue type plasminogen activator (tPA)-mediated plasminogen activation reported previously by several groups. We found nonlinear Eadie-Scatchard plots for Glu plasminogen activation by recombinant single-chain tPA confirming a non-Michaelis Menten behavior of tPA. In order to characterize this mechanism, enzyme kinetic studies with truncated substrates (Lys- and miniplasminogen) and modified or truncated enzymes (two-chain tPA and tPA B-chain) were performed. Thereby it could be excluded that product-mediated modifications of the enzyme or the substrate are responsible for the nonlinear plots. Linear plots, i.e., Michaelis Menten kinetics, were only found when tPA B-chain was used as a plasminogen activator, indicating that the tPA A-chain should be responsible for the non Michaelis-Menten behavior. Binding studies of plasminogen to immobilized tPA A chain in fact demonstrated a saturable binding of Glu- and miniplasminogen to the A-chain of tPA with a KD approximately 0.1 microM and one binding site per molecule of tPA A-chain. These data suggested a modifier mechanism responsible for the nonlinear plots whereby the substrate plasminogen itself could function as a modifier. When such a mechanism was included into a model for tPA-mediated plasminogen activation, the experimentally obtained data could be fitted into such a model by nonlinear regression analysis with resulting p-values of less than 0.001. PMID- 1497340 TI - Purification and characterization of glucosamine-6-phosphate deaminase from dog kidney cortex. AB - Glucosamine-6-phosphate deaminase (EC 5.3.1.10) from dog kidney cortex was purified to homogeneity, as judged by several criteria of purity. The purification procedure was based on two biospecific affinity chromatography steps, one of them using N-epsilon-amino-n-hexanoyl-D-glucosamine-6-phosphate agarose, an immobilized analog of the allosteric ligand, and the other by binding the enzyme to phosphocellulose followed by substrate elution, which behaved as an active-site affinity chromatography. The enzyme is an hexameric protein of about 180 kDa composed of subunits of 30.4 kDa; its isoelectric point was 5.7. The sedimentation coefficient was 8.3S, and its frictional ratio was 1.28, indicating that dog deaminase is a globular protein. The enzyme displays positive homotropic cooperativity toward D-glucosamine-6-phosphate (Hill coefficient = 2.1, pH 8.8). Cooperativity was completely abolished by saturating concentrations of GlcNAc6P; this allosteric modulator activated the reaction with a typical K-effect. Under hyperbolic kinetics, a Km value of 0.25 +/- 0.02 mM for D-glucosamine-6-phosphate was obtained. Assuming six catalytic sites per molecule, kcat is 42 s-1. Substrate-velocity data were fitted to the Monod's allosteric model for the exclusive-binding case for both substrate and activator, with two interacting substrate sites. The Kdis for N-acetyl-D-glucosamine-6-phosphate was estimated at 14 microM. PMID- 1497341 TI - Proteolysis with trypsin of mammalian tyrosinase isoforms from B16 mouse melanoma. AB - In spite of the central role of tyrosinase in mammalian pigmentation, few data are available on its structure and structure-function relationships based on direct analysis of the protein. A number of reasons have been invoked to account for this situation, including the problems for its purification and its resistance to proteases. However, no study on the effects of proteases on purified tyrosinase has been reported. We have purified the melanosomal and cytosolic tyrosinases from B16 mouse melanoma and analyzed their susceptibility to trypsin digestion. Both isoforms are sensitive to trypsin, and display similar peptide maps and kinetics of proteolysis, suggesting that they are products of the same gene. The peptide maps and the kinetics of appearance of the fragments were consistent with the sequential removal of N-terminal peptides, leading to a core of 55.3 kDa for the melanosomal form and 48.6 kDa for the cytosolic enzyme. This core was apparently resistant to further proteolysis and catalytically inactive. The difference in molecular weight for the core of the cytosolic and melanosomal forms is the same as that calculated for the native isoforms. The kinetics of enzyme inactivation indicate that the tyrosine hydroxylase and Dopa oxidase activities of tyrosinase are lost at the same rate, and should therefore display similar if not identical structural requirements. The results are discussed in terms of the relationship of both isoforms and of the putative protein sequences deduced from the cDNA clones proposed for tyrosinase. PMID- 1497342 TI - Degradation of rat liver cytochromes P450 3A after their inactivation by 3,5 dicarbethoxy-2,6-dimethyl-4-ethyl-1,4-dihydropyridine: characterization of the proteolytic system. AB - The suicide substrate 3,5-dicarbethoxy-2,6-dimethyl-4-ethyl-1,4- dihydropyridine (DDEP) inactivates rat liver cytochrome P450 (P450) 3A isozymes through prosthetic heme alkylation of the apoprotein in a mechanism-based fashion, which marks them for rapid proteolysis. In this article, through the use of epitope specific monoclonal antibodies, we show that both 3A1 and 3A2 isozymes are targeted for proteolysis. Furthermore, using intact rats, isolated rat hepatocytes, and rat liver subcellular fractions supplemented with ATP and MgCl2, as well as various proteolytic inhibitors as probes, we now report that the hepatic cytosolic ubiquitin-dependent proteolytic system rather than hepatic lysosomes is involved in the rapid degradation of DDEP-induced heme alkylated P450s 3A. PMID- 1497343 TI - Location and characterization of multiple glucocorticoid-responsive elements in the rat serine dehydratase gene. AB - Transcription of the gene coding for serine dehydratase (SDH, EC 4.2.1.13) in the rat in vivo is dramatically increased by glucocorticoid hormones. To identify DNA elements mediating the glucocorticoid-regulated expression of the SDH gene, we transiently transfected 7AD-7 rat hepatoma cells with fusion genes consisting of various regions of the SDH 5' flanking sequence linked to the coding sequence of the gene for chloramphenicol acetyltransferase (CAT). Analysis of the CAT activities from these 5' deletion mutants identified three closely associated glucocorticoid-responsive elements (GREs), located more than 5 kb upstream relative to the cap site. Two distal GREs act synergistically to confer strong glucocorticoid inducibility to the gene, whereas the proximal GRE functions independently of the distal GREs and confers only a weak hormone response to the gene. The purified DNA-binding domain of rat glucocorticoid receptor binds to the sequence of each GRE as shown by footprinting experiments. However, only one of these sequences contains the TGTTCT consensus sequence reportedly associated with many other GREs. PMID- 1497344 TI - Polyvanadate-stimulated NADH oxidation by plasma membranes--the need for a mixture of deca and meta forms of vanadate. AB - Polyvanadate solutions obtained by extracting vanadium pentoxide with dilute alkali over a period of several hours contained increasing amounts of decavanadate as characterized by NMR and ir spectra. Those solutions having a metavanadate:decavanadate ratio in the range of 1-5 showed maximum stimulation of NADH oxidation by rat liver plasma membranes. Reduction of decavanadate, but not metavanadate, was obtained only in the presence of the plasma membrane enzyme system. High simulation of activity of NADH oxidation was obtained with a mixture of the two forms of vanadate and this further increased on lowering the pH. Addition of increasing concentrations of decavanadate to metavanadate and vice versa increased the stimulatory activity, reaching a maximum when the metavanadate:decavanadate ratio was in the range of 1-5. Increased stimulatory activity can also be obtained by reaching these ratios by conversion of decavanadate to metavanadate by alkaline phosphate degradation, and of metavanadate to decavanadate by acidification. These studies show for the first time that both deca and meta forms of vanadate present in polyvanadate solutions are needed for maximum activity of NADH oxidation. PMID- 1497345 TI - Fungal quinone pigments as oxidizers and inhibitors of mitochondrial NADH:ubiquinone reductase. AB - The interaction of fungal quinone pigments bostricoidin, fusarubin, javanicin, and 2-oxyjuglone with mitochondrial NADH:ubiquinone reductase (complex I, EC 1.6.99.3) has been studied. The bimolecular rate constants (turnover number (TN)/Km) of rotenone-insensitive reduction of these compounds are in the range of 1.2 x 10(4)-1.6 x 10(5) M-1s-1. 2-Oxyjuglone acts as inhibitor of NADH:ferricyanide reductase reaction of complex I (KI = 30 microM). All quinone pigments, except javanicin, decrease the TN of reduction of 5,8-dioxy-1,4 naphtoquinone being reduced at its binding site but with significantly lower TN. They do not affect the rotenone-sensitive reduction of ubiquinone-1. The binding of quinone pigments close to the NADH and ferricyanide binding site is suggested. It seems that quinone pigments, especially 2-oxyjuglone, react with complex I faster than it follows from their approximate values of one-electron reduction potential calculated from their reactivities with flavocychrome b2 and adrenodoxin. PMID- 1497346 TI - Effect of hydrogen peroxide on calcium homeostasis in smooth muscle cells. AB - One of the major biological targets of free radical oxidations, prone, for anatomical reasons, to oxidative challenges, is the cardiovascular system. In the present paper the effect of hydrogen peroxide on intracellular ionized calcium ([Ca2+]i) homeostasis in smooth muscle cells (SMC) is studied, the major aim of the study being a better understanding of the protective effect of antioxidants and Ca2+ channel blockers. The exposure of SMC to 300 microM H2O2 induced a rapid increase of [Ca2+]i, followed by a decrease to a new constant level, higher than the basal before the oxidative challenge. When incubation medium was Ca2+ free, the pattern of [Ca2+]i change was different. The rapid increase was still observed, but it was followed by a rapid decrease to a level only slightly above the basal before the oxidative challenge. The involvement of intracellular Ca2+ stores was tested by using vasopressin, a hormone able to induce discharge of inositol 1,4,5-triphosphate-sensitive Ca2+ stores. When H2O2 was added after vasopressin no [Ca2+]i increase was observed. Treatment of cells, in which the stable increase of [Ca2+]i was induced by H2O2, with disulfide reducing compounds, induced a progressive decrease of [Ca2+]i toward the level observed before the oxidative challenge. Calcium channel blockers and antioxidants, on the other hand, effectively prevented the stabilization of [Ca2+]i at the high steady state, after the internal Ca2+ release phase. Dihydropyridine Ca2+ channel blockers were by far more active than verapamil and among those the most active was lacidipine. Also the antioxidants trolox and N,N'-diphenyl-1,4 phenylenediamine both prevented the [Ca2+]i unbalance. These results suggest that Ca+ channel blockers and antioxidants, although inactive on oxidative stress induced Ca2+ release from intracellular stores, prevent the increased influx apparently related to a membrane thiol oxidation. PMID- 1497347 TI - Localization of two binding domains for thrombospondin within fibronectin. AB - Thrombospondin is a major glycoprotein of the platelet alpha-granule and is secreted during platelet activation. Several protease-resistant domains of thrombospondin mediate its interactions with components of the extracellular matrix including fibronectin, collagen, heparin, laminin, and fibrinogen. Thrombospondin, as well as fibronectin, is composed of several discretely located biologically active domains. We have characterized the thrombospondin binding domains of plasma fibronectin and determined the binding affinities of the purified domains; fibronectin has at least two binding sites for thrombospondin. Thrombospondin bound specifically to the 29-kDa amino-terminal heparin binding domain of fibronectin as well as to the 31-kDa non-heparin binding domain located within the larger 40-kDa carboxy-terminal fibronectin domain generated by chymotrypsin proteolysis. Platelet thrombospondin interacted with plasma fibronectin in a specific and saturable manner in blot binding as well as solid phase binding assays. These interactions were independent of divalent cations. Thrombospondin bound to the 29-kDa fibronectin heparin binding domain with a Kd of 1.35 x 10(-9) M. The Kd for the 31-kDa domain of fibronectin was 2.28 x 10(-8) M. The 40-kDa carboxy-terminal fragment bound with a Kd of 1.65 x 10(-8) M. Heparin, which binds to both proteins, inhibited thrombospondin binding to the amino-terminal domain of fibronectin by more than 70%. The heparin effect was less pronounced with the non-heparin binding carboxy-terminal domain of fibronectin. By contrast, the binding affinity of the thrombospondin 150-kDa domain, which itself lacked heparin binding, was not affected by the presence of heparin. Based on these data, we conclude that thrombospondin binds with different affinities to two distinct domains in the fibronectin molecule. PMID- 1497348 TI - Primary structure of locust flight muscle fatty acid binding protein. AB - The amino acid sequence of the fatty acid binding protein (FABP) from flight muscle of the locust, Schistocerca gregaria, has been determined. The sequence of the N-terminal 39 amino acid residues, determined by automated Edman degradation, was used to prepare a degenerate oligonucleotide that corresponded to amino acid residues 16-23. cDNA coding for FABP was constructed from flight muscle mRNA and amplified by the polymerase chain reaction using the degenerate oligonucleotide and an oligo dT-NotI primer adapter as primers. The amplification product was cloned and sequenced. Additionally, a cDNA library of flight muscle mRNA was prepared and screened with a 414-bp probe prepared from the clone. The primary structure of locust FABP was compared with the proteins in the Swiss protein databank and found to have significant homology with mammalian FABPs over the entire 133-residue sequence. The best match was versus human heart FABP (41% identity), attesting to the highly conserved nature of this protein. The results suggest that locust muscle FABP is a member of the lipid binding protein superfamily and may provide valuable insight into the evolution of this abundant protein class. PMID- 1497349 TI - Astaxanthin and canthaxanthin are potent antioxidants in a membrane model. AB - When the conjugated keto-carotenoids, either astaxanthin or canthaxanthin, are added to rat liver microsomes undergoing radical-initiated lipid peroxidation under air, they are as effective as alpha-tocopherol in inhibiting this process. This contrasts with the effect of beta-carotene, which is a much less potent antioxidant when added in this system, without the addition of other antioxidants. PMID- 1497350 TI - Association of a heat-stable inhibitor protein with cyclic-3',5'-AMP-dependent protein kinase from the nematode Ascaris suum: purification and characterization of the inhibitor. AB - An inhibitor protein of the catalytic subunit of the cyclic 3',5'-AMP-dependent protein kinase from the nematode Ascaris suum was isolated and characterized. The molecular weight of the inhibitor was estimated as 28,000 by electrophoresis under denaturing conditions and as 30,000 by gel permeation chromatography on Superose 12. The Trypsin-labile inhibitor was resistant to short incubations (less than or equal to 5 min) at temperatures up to 95 degrees C and at pH 3. It affected the protein kinase from Ascaris and bovine heart with almost the same affinity, and inhibition was not relieved by the presence of cAMP and cGMP. However, the inhibition was antagonized by low concentrations of heparin. Unlike in mammalian tissues, the concentration of the inhibitor was sufficiently high to exert at least 90% inhibition of the protein kinase activity in Ascaris muscle. Therefore, the inhibitor may play a role in cellular regulation in the nematode. PMID- 1497351 TI - Studies on geranylgeranyl diphosphate synthase from rat liver: specific inhibition by 3-azageranylgeranyl diphosphate. AB - Geranylgeranyl diphosphate synthase from rat liver was separated from farnesyl diphosphate synthase, the most abundant and widely occurring prenyltransferase, by DEAE-Toyopearl column chromatography. The enzyme catalyzed the formation of E,E,E-geranylgeranyl diphosphate (V) from isopentenyl diphosphate (II) and dimethylallyl diphosphate (I), geranyl diphosphate (III), or farnesyl diphosphate (IV) with relative velocities of 0.09:0.15:1. 3-Azageranylgeranyl diphosphate (VII), designed as a transition-state analog for the geranylgeranyl diphosphate synthase reaction, was synthesized and found to act as a specific inhibitor for this synthase, but not for farnesyl diphosphate synthase. Diphosphate V and its Z,E,E-isomer (VI) also inhibited geranylgeranyl diphosphate synthase, but the effect was not as striking as that of the aza analog VII. Specific inhibition of geranylgeranyl diphosphate synthase by VII was also observed in experiments with 100,000g supernatants of rat brain and liver homogenates which contained isopentenyl diphosphate isomerase and prenyltransferases including farnesyl diphosphate synthase as well as geranylgeranyl diphosphate synthase. For farnesyl:protein transferase from rat brain, however, the aza compound did not show a stronger inhibitory effect than E,E,E-geranylgeranyl diphosphate. PMID- 1497352 TI - Thyroid peroxidase glycosylation: the location and nature of the N-linked oligosaccharide units in porcine thyroid peroxidase. AB - Highly purified, trypsin/detergent-solubilized thyroid peroxidase (TPO), prepared from pig thyroid tissue, was subjected to reduction and alkylation followed by trypsin digestion. The resulting peptides were fractionated using HPLC. Corresponding carbohydrate positive regions from three separate HPLC experiments were pooled and further chromatography was carried out to yield purified peptide suitable for sequence analysis and complete carbohydrate composition analysis. Four of the five putative sites for N-linked glycosylation were found to carry oligosaccharide units in which mannose and glucosamine were the sole or predominant sugars. Three of the four glycosylations occur at asparagine residues which are likely to be at beta turns or bends. The fifth putative glycosylation site could not be confirmed and may either be poorly glycosylated or escape glycosylation. All of the confirmed glycosylated sites occur in the N-terminal third of the TPO polypeptide chain, in the portion of the molecule believed to be extracellular. The isolation of at least two chromatographic forms of glycopeptide derived from each of the confirmed sites suggests microheterogeneity in the structure of the oligosaccharide units of thyroid peroxidase similar to that observed in many other glycoproteins. PMID- 1497353 TI - Regulation of phospholipase C delta activity by sphingomyelin and sphingosine. AB - Phospholipase C delta (PLC delta) is strongly inhibited by sphingomyelin (SM). The inhibition occurs in both the presence and the absence of spermine, an activator of PLC delta. Phosphatidylethanolamine (PE), phosphatidylcholine (PC), phosphatidylserine (PS), and phosphatidylinositol (PI) also inhibit PLC delta in the presence of spermine but are much less effective than SM. PE and PC activate and PS and PI inhibit PLC delta in the absence of spermine. Again, the inhibition by PS and PI is much weaker than the inhibition observed with SM. Similar or identical effects are observed in detergent micelle and liposome assays. Comparisons of physiological concentrations of SM with concentrations yielding 50% inhibition of PLC delta in vitro indicate that SM is likely to be a major factor in regulating the activity of PLC delta by inhibition. It is proposed that, in vivo, sphingomyelin acts as an inhibitor of PLC delta, which enables the enzyme to be regulated by activation. In certain circumstances, there is a substantial decline in SM and this may lead to a partial relief of the inhibition. PLC delta is activated by sphingosine in the absence of spermine. However, this activation occurs at unphysiologically high concentrations of sphingosine. The effects of SM and sphingosine on PLC delta in marked contrast to those observed with protein kinase C, which is unaffected by sphingomyelin and inhibited by sphingosine. PMID- 1497354 TI - Fragmentation of dimyristoylphosphatidylcholine vesicles by apomyoglobin. AB - Previously we have reported results of a preliminary study on the micellization of phosphatidylcholine vesicles by apomyoglobin at pH 4 (J. W. Lee and H. Kim, 1988, FEBS Lett. 241, 181-184). The micellization study has been extended here to investigate the effect of the lipid to protein ratio, temperature, size of vesicles, and pH. The pH-dependent study indicated that micellization occurs when the protein assumes either a molten globular or random coil structure. Time dependent hydrophobic labeling by 3-(trifluoromethyl)-3-(m-[125I]iodophenyl) diazirine showed that there is an initial increase in contact between the protein and hydrophobic acyl chain of lipid followed by a decrease in the interaction. This may be explained as the initial stage of vesicle aggregation which is subsequently superseded by the fragmentation. These reactions are discussed in term of protein unfolding at low pH. PMID- 1497355 TI - The chelation of nonheme iron within sickle erythrocytes by the hydroxypyridinone chelator CP094. AB - Nonheme, nonferritin iron has been detected in membrane preparations from sickle erythrocytes and has been suggested to catalyze free radical reactions in these cells contributing to the development of membrane oxidation. In this study the hydroxypyridinone iron chelator, CP094, currently being evaluated as a potentially therapeutic chelator, and desferrioxamine have been studied for their abilities to chelate the nonheme iron within intact sickle erythrocytes under physiological conditions. The results suggest that CP094 can enter sickle erythrocytes, chelate nonheme iron and suppress membrane lipid peroxidation within a timescale in which desferrioxamine does not enter the cells. Suppression of lipid peroxidation showed no protective effect in an in vitro system inducing the formation of irreversibly sickled cells. PMID- 1497356 TI - Novel protein inhibits in vitro precipitation of calcium carbonate. AB - Organic molecules both coexist and interact with inorganic crystal lattices in biomineralizing tissues. Mineral precipitation and crystal morphology are tightly regulated by the actions of these molecules. Polyacrylamide gel electrophoresis studies on water soluble extracts from the cuticle of Callinectes sapidus (Atlantic blue crab) reveal the presence, in unmineralized nascent premolt cuticle, of proteins which are absent in the mineralized postmolt cuticle. In the present studies, homogenates from both premolt and postmolt C. sapidus cuticles have been tested for their effect on the in vitro precipitation of calcium carbonate. The role of protein in this process was determined by heat pretreatment and trypsin pretreatment of the cuticle homogenates prior to the precipitation assay. The results from these experiments indicate that proteins, with molecular weights of approximately 75,000 and between 10,000 and 20,000, concentrated in the C. sapidus premolt cuticle, inhibit calcium carbonate precipitation in vitro. The inhibitory activity of these proteins appears to be a result of specific interactions since trypsin, myoglobin, and ovalbumin are not inhibitory. The presence of lower amounts of these inhibitory proteins in C. sapidus postmolt cuticle may be responsible for the subsequent mineralization of this tissue. PMID- 1497357 TI - Fluconazole treatment of cutaneous cryptococcosis. PMID- 1497359 TI - Treatment of pyoderma gangrenosum with cyclosporine. AB - BACKGROUND AND DESIGN: Pyoderma gangrenosum is a chronic inflammatory ulcerative skin disease of unknown origin, often associated with various diseases including inflammatory bowel disease, inflammatory arthritis, monoclonal gammopathies, hepatitis, and myeloproliferative disorders. Treatment of associated systemic disorders may improve the ulcers, but lesions may be recalcitrant and persist for months to years. Therapy for pyoderma gangrenosum includes high-dose systemic corticosteroids, sulfa drugs such as sulfasalazine, clofazimine, and immunosuppressive agents such as mercaptopurine and azathioprine; these drugs are sometimes ineffective. RESULTS: We present a series of 11 patients with pyoderma gangrenosum, with a wide range of underlying diseases, whose ulcers were refractory to usual therapy and who were treated with low-dose cyclosporine. Ten of the 11 patients cleared rapidly and completely with cyclosporine therapy. CONCLUSIONS: Cyclosporine should be seriously considered as a primary form of treatment for pyoderma gangrenosum. PMID- 1497358 TI - Cutaneous reactions to granulocyte-monocyte colony-stimulating factor. AB - BACKGROUND AND DESIGN: Granulocyte-monocyte colony-stimulating factor (GMCSF) is a hematopoietic growth factor that stimulates the proliferation and differentiation of neutrophils, eosinophils, and monocytes. We reviewed the cutaneous reactions that developed in 26 patients who received GMCSF as part of a chemotherapeutic protocol. RESULTS: Fourteen patients developed immediate localized angioedematous reactions at the subcutaneous GMCSF injection site, and 21 developed generalized cutaneous reactions. Four biopsy specimens were obtained from three patients who had generalized erythrodermic reactions. All specimens showed perivascular and periadnexal lymphocytic inflammation in the dermis, and two showed perivascular and periadnexal eosinophilia. Staining for eosinophil granule major basic protein showed infiltration by eosinophils and extracellular deposition of major basic protein in three specimens from two patients with eosinophilia. Extracellular deposition of neutrophil elastase and mast cell tryptase was minimal. CONCLUSIONS: Cutaneous reactions are prominently associated with GMCSF administration. Eosinophils, known to release toxic products after being activated, may have a role in these skin reactions through stimulation by GMCSF. PMID- 1497360 TI - Exogenous origin of n-alkanes in pathologic scale. AB - BACKGROUND: Although n-alkanes accumulate in some disorders of cornification, recent studies using radioactive carbon 14 content by accelerator mass spectrometry point to an exogenous origin for alkanes in normal stratum corneum, and their derivation in congenital ichthyosiform erythroderma remains controversial. DESIGN AND RESULTS: Using 14C content to measure sample age, the n alkane fractions from two patients with congenital ichthyosiform erythroderma contained no detectable contemporary materials. By electron microscopy, alkane enriched emollients (petrolatum [Vaseline]) permeated to all levels of stratum corneum of hairless mice, expanding the intercellular domains and distorting membrane bilayers. Similar ultrastructural changes were also observed in the stratum corneum of patients with congenital ichthyosiform erythroderma. When alkanes were excluded, no differences in lipid content were evident between two forms of autosomal recessive ichthyosis. CONCLUSIONS: These data demonstrate that scale n-alkanes in disorders of cornification derive from environmental sources and indicate the pervasiveness of petroleum-based emollients in skin. Therefore, epidermal lipid analyses must be interpreted with caution. However, these studies do not rule out an important therapeutic and/or pathogenic role for exogenous n alkanes in skin. PMID- 1497361 TI - Alopecia areata. Autoreactive T cells are variably enriched in scalp lesions relative to peripheral blood. AB - BACKGROUND AND DESIGN: Alopecia areata is a condition characterized by hair loss in association with perifollicular infiltration of T cells and antigen-presenting cells. Autoreactive T cells are postulated to amplify this abnormality by interacting with DR+ follicular epithelium. These cells may recognize either autologous major histocompatibility complex class II antigen or an autoantigen restricted by major histocompatibility complex class II. Limiting dilution analysis was used to determine the frequency of autoreactive lymphocytes in scalp biopsy specimens and peripheral blood from seven adult patients with alopecia areata. Autoreactive T cells are defined for this study as those that proliferate in response to autologous irradiated peripheral blood mononuclear cells. RESULTS: Autoreactive lymphocytes were enriched in scalp biopsy specimens relative to peripheral blood in five of seven patients. This enrichment was statistically significant in four of five patients. Five autoreactive T-cell clones derived from lesional scalp were characterized. Four of these clones were CD3+CD4+CD8- and one clone was CD3+CD4-CD8+. CONCLUSIONS: Enrichment of autoreactive cells in lesions of alopecia areata supports a role for these cells in the pathogenesis of this condition. Enrichment of autoreactive lymphocytes is also found in allergic contact dermatitis. Thus, these autoreactive lymphocytes may have a general role in inflammation. PMID- 1497362 TI - Focal dermal hypoplasia syndrome in a male patient. Report of a case and histologic and immunohistochemical studies. AB - BACKGROUND: Focal dermal hypoplasia (FDH) is a rare ectomesodermal dysplasia syndrome characterized by cutaneous, skeletal, dental, ocular, and soft-tissue defects. An X-linked dominance with death of male subjects has been assumed as the mode of inheritance. Only a few cases of FDH have been reported in male subjects. A 68-year-old man had typical skin lesions of FDH. Clinical, histologic, and immunohistochemical features are presented. OBSERVATIONS: The cutaneous abnormalities consisted of atrophic hyperpigmented and hypopigmented macules and erythematous, slightly raised lesions showing a highly characteristic linear distribution. Other abnormalities, including syndactyly, apocrine hidrocystoma of eyelids, and bilateral cholesteatoma were observed. Only one case of FDH in association with an apocrine hidrocystoma has been reported previously. Consistent findings microscopically in the erythematous lesions were areas of scar formation with subepidermal bulla overlying the neodermis. A strongly positive immunohistochemical reaction for vimentin, fibronectin, and collagen type III was observed in the scar tissue. No collagen type IV was detected in the basement membrane zone of the epidermis covering the lesion. CONCLUSION: It has been proposed that fibroblastic abnormalities may lead to an alteration of collagen synthesis in FDH, although confirmation of this hypothesis was unavailable. Our findings suggest that production of collagen type IV may be delayed in FDH resulting from a fibroblastic defect. PMID- 1497363 TI - The pyloric atresia-junctional epidermolysis bullosa syndrome. Report of a case and review of the literature. AB - BACKGROUND AND METHODS: The concomitant occurrence of the two rare conditions of pyloric atresia (PA) and inherited epidermolysis bullosa (EB) is not as rare as would be expected. We collected 41 case reports in the world literature and add a personal case in which EB was investigated with modern methods and found to be a GB3-positive/non-Herlitz junctional variant. OBSERVATIONS: Our review of the PA EB association discloses that it is an autosomal recessive inherited entity in which EB is of the junctional EB (JEB) subtype and PA is a primary manifestation rather than a scarring process secondary to JEB. The disease is thus better called "PA-JEB." Patients with the PA-JEB syndrome present, not uncommonly, with erosions and/or subepithelial cleavage in the respiratory, gastrointestinal, and urinary tracts. In addition, certain facultative features are unique to PA-JEB, ie, obstruction of the ureterovesical junction and high incidence of a peculiar form of aplasia cutis congenita. CONCLUSION: The GB3 monoclonal antibody was found normally expressed in three of three cases, excluding the Gravis-Herlitz variant, in spite of an unmatching EB phenotype in one case. Further studies are needed to assess which of the JEB varieties are present in the PA-JEB syndrome. PMID- 1497364 TI - Congenital localized absence of the skin as a manifestation of epidermolysis bullosa. AB - BACKGROUND: Congenital localized absence of the skin has been observed in various subsets of inherited epidermolysis bullosa. Through electron microscopy and immunomapping, we attempt to clarify the relationship of congenital localized absence of the skin lesions to epidermolysis bullosa. OBSERVATIONS: The case of a child with epidermolysis bullosa simplex and congenital localized absence of the skin is presented. Electron microscopy and immunomapping of the areas of congenital localized absence of the skin and sites of skin fragility suggest that these lesions are pathogenically identical. CONCLUSION: After reviewing the literature, we believe that the term Bart's syndrome should be used to identify patients with any type of epidermolysis bullosa who present with localized congenital absence of the skin on the extremities. PMID- 1497365 TI - Histologic features of paraneoplastic pemphigus. AB - BACKGROUND: We describe the histopathologic features of paraneoplastic pemphigus, a recently described autoimmune mucocutaneous disease associated with neoplasia. Complete evaluation for paraneoplastic pemphigus requires identification of the characteristic mucocutaneous eruption, tissue specimens for routine histologic and direct immunofluorescence evaluation, and identification of circulating autoantibodies with a unique specificity. Immunoprecipitation from keratinocytes reveals a characteristic complex of four proteins with the circulating antibodies. Various neoplasms have been identified in patients with paraneoplastic pemphigus. OBSERVATIONS: We reviewed 16 skin and oral mucous membrane biopsy specimens from six patients with paraneoplastic pemphigus confirmed by fulfillment of all criteria. Major features include epidermal acantholysis, suprabasal cleft formation, dyskeratotic keratinocytes, vacuolar change of the basilar epidermis, and epidermal exocytosis of inflammatory cells. Seven (44%) of 16 specimens displayed a unique combination of suprabasal acantholysis and dyskeratotic keratinocytes throughout the epidermis. These histologic findings correspond to those of the characteristic clinical lesions that are described as having features of pemphigus and erythema multiforme. CONCLUSIONS: Paraneoplastic pemphigus represents a unique clinical, histologic, and immunologic disease characterized by autoantibody production to desmoplakin I and desmoplakin II, bullous pemphigoid antigen, and, possibly, other antigens in the desmosomal complex. Recognition of the histologic features should prompt immunopathologic confirmation and evaluation for an occult neoplasm. PMID- 1497367 TI - Faces going up in smoke. A dermatologic opportunity for cancer prevention. PMID- 1497366 TI - Medical education for congressional aides and other governmental health policymakers. PMID- 1497368 TI - Focal dermal hypoplasia syndrome. An update. PMID- 1497369 TI - Fluctuant nodules and alopecia of the scalp. Perifolliculitis capitis abscedens et suffodiens. PMID- 1497370 TI - An unusual case of pruritus ani. Anal margin squamous cell carcinoma (SCC). PMID- 1497371 TI - Pruritic ulcerating bruise in an elderly Hispanic man. Angiosarcoma (AS). PMID- 1497372 TI - Progressive perianal ulceration. Ergotism (ergotismus gangraenosus). PMID- 1497373 TI - Multiple plaques of morphea developing in a patient with eosinophilic fasciitis. PMID- 1497374 TI - The rule of hand: 4 hand areas = 2 FTU = 1 g. PMID- 1497375 TI - Serum vitamin A levels in psoriasis: results from the First National Health and Nutrition Examination Survey. PMID- 1497376 TI - Vehicular traffic as a determinant of blood-lead levels in children: a pilot study in Mexico City. AB - The major determinants of blood-lead levels were studied in 90 children who attended an outpatient pediatric clinic in Mexico City. All children, who were from 1-10 y of age, were from homes for which socioeconomic status had been categorized as medium to high. Blood-lead levels ranged from 0.17 (standard deviation [SD] = 0.008) to 1.21 (SD = 0.06 mumol/l). The main determinant of blood-lead levels was place of residence. Children who lived on private streets (i.e., low-traffic areas) had a significantly lower blood-lead level than children who lived on large avenues and who resided close to main roads (p = .0001, r2 = .27). This observation documented high exposure levels among children who live in Mexico City and suggested that leaded fuel used in Mexico could play an important role in determining blood-lead levels in this population. PMID- 1497378 TI - Repeated bone lead levels in Queensland, Australia--previously a high lead environment. AB - Bone lead levels (finger and tibia) were measured, both in vivo and in vitro, with an x-ray fluorescence technique. In vivo finger-bone lead levels of 105 volunteers were estimated and subsequently re-estimated after a 5-y period. In many instances, elevated levels in some of these individuals probably resulted from lead ingested during childhood (i.e., more than 60 y ago). A decline in finger-bone lead from the initial value was accompanied by a mean finger-bone lead half-life of 6.2 y (n = 25); many individual's half-life values were less than 3.0 y. Perhaps one reason for these low values is the special propensity of finger bone to resorption during the involutional period, at which time there are high levels of circulating parathormone. PMID- 1497377 TI - Placental cadmium and birthweight in women living near a lead smelter. AB - It has been suggested that the accumulation of tobacco-derived cadmium (Cd) in the placenta is responsible for the adverse effect of cigarette smoking on infant birthweight. We chose to test this hypothesis; therefore, we studied a population of nonsmoking pregnant women who were exposed to low levels of smelter-derived Cd and a group of nonexposed women. A higher mean placental Cd concentration (p less than .0007) was found in the exposed women (n = 106), compared with those who were not exposed (n = 55); the observed Cd concentrations were comparable to concentrations reported previously for smoking and nonsmoking women, respectively. Least squares multiple regression (controlling for potentially confounding variables) revealed no association between placental Cd and birthweight. It was, therefore, concluded that the effect of smoking on birthweight was not mediated through Cd. PMID- 1497379 TI - Reported symptom prevalence rates from comparison populations in community-based environmental studies. AB - National, regional, state, and county rates of mortality and morbidity are frequently used as reference values in epidemiologic studies. However, baseline information on self-reported symptom rates is currently unavailable. This information is potentially very useful as outcome measures in environmental and occupational epidemiologic studies in which symptoms may be the most sensitive measure of effects of low-level chemical exposure. Comparison populations (n = 934 adults) from three community-based studies were used to determine 1-y symptom prevalence rates. Symptoms rates varied greatly between one study, in which a self-administered questionnaire was used, and the two studies for which data were collected via a similar questionnaire administered by trained interviewers. Four symptoms were selected for detailed analysis of covariates associated with symptom reporting: (1) skin irritation, (2) eye irritation, (3) sleep disturbance, and (4) fatigue. Logistic regression analysis of symptom reporting, by demographic data, and a risk perception variable suggested that the prevalence of symptoms varied with gender, race, and degree of respondent's environmental concern. The results from two of three surveys provide rates that might be used as reference rates in a community-based survey if resources are not available to permit the study of a comparison population. These rates may also provide a quick, initial impression prior to embarking on a full-scale epidemiologic study. PMID- 1497380 TI - A study of current residents' knowledge of a former environmental health survey of their community. AB - A follow-up survey of current residents who live near the McColl waste disposal site was conducted to assess community knowledge of an environmental health survey that occurred in the same neighborhood 7 y earlier. Of the 193 eligible adults who participated in an interview (response rate = 73.4%), 35.8% reported having heard of the 1981 health survey; 48% of these (n = 33) reported hearing or seeing the results of the survey. Knowledge of the earlier survey was reported by 34.6%, 40.6%, and 35.7% of respondents in the high-exposure, low-exposure, and comparison areas, respectively. Recall was significantly associated with age (i.e., greater than 55 y), college education, and residence prior to 1981. Our findings suggest that both long-term and recent residents in the study areas know about the McColl waste-disposal site, but the majority of current residents in this sample do not know that the health of the community was assessed in 1981 and that no serious health effects associated with the site were identified. Future efforts to communicate findings of similar health studies should focus on individuals who have less education and on communication with residents who move into an area after a study has been conducted. Creative public participation and media relations should be developed to assure that the results of such studies reach the public. PMID- 1497381 TI - Assessment of acute health effects from the Medfly Eradication Project in Santa Clara County, California. AB - Surveys were performed to assess the acute health effects of aerial application of malathion bait over a large urban area. Three indirect attempts to assess utilization of health care services were made: (1) surveillance of a major hospital emergency department was undertaken, (2) ambulance dispatches were reviewed, and (3) emergency treatments for asthma at a university hospital were reviewed. These assessments were negative but insensitive. Prevalence of self reported symptoms was assessed with two surveys that were subject to severe time constraints. Personal interviews of the same individuals, before and after the spraying, were conducted: one was conducted by telephone and the other by residential visit. Results indicated no detectable increase in acute morbidity. Also, after the spraying, there was a decrease in anxiety-related symptoms. PMID- 1497382 TI - Investigation of a reported cluster of bladder cancer cases in the Pottstown/Phoenixville area of Pennsylvania. AB - A urologist in Phoenixville, Pennsylvania, noted an apparent excess of invasive bladder cancer cases in his practice area during 1988 and 1989. Background incidence data for the local area were derived from state Cancer Registry statistics. Seventeen additional cases were noted during review of local hospital tumor registry data. Exposure evaluation included complete occupational histories for 15 index cases and correlation of residential histories with a review of local industries, water quality data, and toxic waste sites. The data were compared with incidence data from 1984 and 1985, and no increase in bladder cancer incidence for this area in 1988 and 1989 was evident. There was, however, a higher bladder cancer incidence among white males in the study area and Chester County, compared with Pennsylvania as a whole. Residential histories and environmental analysis did not reveal a common environmental carcinogen. A high incidence of occupational exposure to suspected bladder carcinogens was noted. In addition, all but 4 of the index cases smoked cigarettes. The study was limited by an extreme paucity of water supply analysis data. Effective environmental monitoring would promote more effective research into environmental carcinogenesis. PMID- 1497383 TI - Gastric cancer mortality and nitrate levels in Wisconsin drinking water. AB - The association between nitrate levels in public and private sources of drinking water and gastric cancer mortality in Wisconsin was investigated in a case control study. All gastric cancer deaths of Wisconsin residents from 1982 through 1985 were compared with deaths from other causes (controls), and nitrate levels in the home drinking water of these residents were determined. Nitrate measures for public sources were obtained from historic nitrate data from municipal sources that existed in 1970. Nitrate measures for private water sources were obtained by testing the wells individually at the existing residences. Controls were matched individually to gastric cancer cases with respect to sex, year of birth, year of death, Wisconsin birth, and Wisconsin residency at the time of death. Matched-pair analyses were performed on the paired data, and the following levels of nitrate-nitrogen exposure were used as indicators of exposure: 0.5, 2.5, 5.0, and 10.0 mg/l. Matched-pair analysis was also performed for which private water supply constituted exposure. Odds ratios and 95% confidence intervals were, respectively, 0.92 (0.75, 1.12); 0.97 (0.74, 1.35); 0.86 (0.69, 1.08); 1.50 (0.12, 18.25); and 1.09 (0.82, 1.47) for exposure to private well water sources. These results did not indicate an increased risk of gastric cancer at any level. PMID- 1497384 TI - Immune alterations in humans exposed to the termiticide technical chlordane. AB - Lymphocyte phenotype frequencies and in vitro functional assays were studied in 27 individuals who had been exposed to technical chlordane in their homes or at their places of work. A control group consisted of 118 individuals who were similar to the exposed group with respect to age and sex distribution, and who had not knowingly experienced exposure to technical chlordane, was chosen for study. A significantly increased frequency of cortical thymocytes in the circulation (CD1) (p less than .001) and a decreased frequency of the suppressor inducer phenotype CD45RA/T4 (p less than .01) were noted in the exposed group. Both kappa and lambda light-chain frequencies were elevated (p less than .01). Proliferative responses to the three mitogens tested, PHA, CONA, PWM, and to allogeneic lymphocytes in the mixed-lymphocyte culture assay were significantly lower than in controls (p less than .01). Responses in assays of the natural killer function were not significantly different from those of controls, but Fc receptor-associated K cell function was significantly greater than responses in controls. Of 12 individuals tested for evidence of autoimmunity, 11 demonstrated some increased titer of a form of autoantibody. This cluster of significant findings demonstrates the emergence of aberrant peripheral T and B cell regulation and a potential for autoimmune activation, detectable up to 10 y after exposure to technical chlordane. PMID- 1497386 TI - Breath ammonia depletion and its relevance to acidic aerosol exposure studies. AB - It is thought that gaseous ammonia in breath neutralizes acidic air pollution and thereby potentially mitigates the pulmonary effects of pollution. The efficacy of breath ammonia depletion methods reported in recent acid aerosol exposure-health response studies was investigated. Fourteen subjects (21 to 54 y of age) performed one or more of the following hygiene maneuvers: (a) acidic oral rinse (pH 2.5); (b) tooth brushing, followed by acidic oral rinse; (c) tooth brushing, followed by distilled water rinse; and (d) distilled water rinse. Initial ammonia levels ranged from 120 to 1,280 ppb (147-1,570 micrograms/m3). Acidic rinsing resulted in an immediate 90% reduction in exhaled ammonia in all subjects, and a return to 50% of baseline levels occurred within 1 h. Depletion that resulted from tooth brushing or distilled water alone was not significant. It was concluded that acidic oral rinsing is an effective method of reducing airway ammonia, but repeated oral rinsing may be required to maintain consistent, low breath-ammonia conditions during acid aerosol exposure studies. PMID- 1497385 TI - Decontamination of human skin exposed to 2,3,7,8-tetrachlorodibenzo-p-Dioxin (TCDD) in vitro. AB - Human post-mortem skin was exposed in vitro to 2,3,7,8-tetrachlorodibenzo-p dioxin (TCDD) at 32 degrees C, under controlled humidity. In one-half of the samples, damage to the surface of the skin was simulated by stripping of the stratum corneum. After incubation with TCDD for 100 min, four different decontamination protocols were performed: (1) the sample was wiped with dry, adsorbent material (cotton balls); (2) a 10-min topical treatment with mineral oil was followed by dry wiping with cotton balls; (3) a 10-min topical treatment with mineral oil was followed by wiping with acetone-soaked cotton balls; and (4) the sample was washed with water and soap. After decontamination, skin samples were incubated (up to 300 min) again at 32 degrees C. One set of both intact and stripped TCDD-exposed skin samples was incubated for 300 min--absent decontamination--and was used as a control. Mineral oil treatment and acetone wipes, or water and soap, were effective in reducing (i.e., about two-fold) the amount of TCDD in the stratum corneum of intact skin. Mineral oil plus dry wipes reduced the amount of TCDD in the stratum corneum by about one-third, whereas dry wiping alone was ineffective. All protocols, however, were similarly effective in reducing the amount of TCDD in the epidermis and upper dermis; TCDD concentrations were decreased locally by factors of up to ten. In the lower dermis, a minimal effect of the decontamination procedures was observed.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1497387 TI - Effect of benomyl toxicity on some liver constituents of albino rats. AB - Weanling albino rats were fed 0-600 mg/kg body weight methyl 1-(butylcarbamoyl)-2 benzimidazolecarbamate (benomyl) for 7 d, and effects on protein, glycogen, and vitamin A constituents were recorded. Doses fed in rat chow were 0, 40, 80, 125, 165, 200, 240, 280, 320, 360, 400, 440, 480, 520, 560, and 600 mg/kg body weight. There was a dose-dependent decrease in the concentration of liver constituents, of which glycogen decreased the most. Histopathological findings included cellular swelling and edema of the liver, kidney, and spleen. PMID- 1497388 TI - A child's unchildish solution to our cigarette habit. PMID- 1497389 TI - Predisposition to and development and persistence of chronic insomnia: importance of psychobehavioral factors. PMID- 1497390 TI - Calcium antagonists and renal protection. Current status and future perspectives. AB - During the past decade, considerable attention has been focused on the effects of calcium antagonists on renal function. Direct in vivo and in vitro observations in diverse experimental models indicate that calcium antagonists antagonize preglomerular vasoconstriction. Furthermore, calcium antagonists are postulated to have additional properties that contribute to their ability to afford renal protection. These putative mechanisms include the ability to retard renal growth, and possibly to attenuate mesangial entrapment of macromolecules, and to attenuate the mitogenic effects of diverse growth factors. Although the clinical implications of the above-mentioned findings have not been fully delineated, the results of recent clinical trials indicate that calcium antagonists exert salutary effects on renal function in clinical settings characterized by impaired renal hemodynamics, including transplant-associated acute renal insufficiency and, possibly, cyclosporine nephrotoxicity. Evidence has accrued suggesting that calcium antagonists may also be protective against acute radiocontrast-induced nephrotoxicity. Finally, the renal hemodynamic and natriuretic effects of calcium antagonists commend their use as antihypertensive agents in the management of essential hypertension, renovascular hypertension, and transplant-associated hypertension. PMID- 1497391 TI - Current status of lung transplantation for cystic fibrosis. AB - Lung transplantation has emerged as an acceptable option for the management of cystic fibrosis patients with endstage lung disease. Heart-lung transplantation and, more recently, double lung transplantation have been successfully performed in this group of patients. The choice of operation, so far, has been based on the surgeon's preference and experience as well as the cardiac function of the patient. Each of the procedures has advantages and disadvantages. This article reviews the current worldwide experience in lung transplantation for patients with cystic fibrosis and highlights the controversies involved in the selection of patients and procedure. PMID- 1497392 TI - Optimal therapeutic level of heparin therapy in patients with venous thrombosis. AB - BACKGROUND: Audits of heparin sodium therapy suggest that heparin administration is fraught with difficulty. The literature indicates that the current clinical practice of intuitive ordering of heparin results in inadequate therapy because of fear of bleeding. The importance of exceeding the lower limit of the therapeutic range has been strongly supported by findings of prospective clinical trials. Firm evidence indicates that failure to exceed the lower limit is associated with unacceptably high rates of recurrent venous thromboembolism. By comparison, evidence supporting the risk of exceeding the upper limit of the therapeutic range is weak. OBJECTIVES: The purposes of this study were (1) to validate prospectively an approach designed to minimize the proportion of patients receiving subtherapeutic doses of heparin and (2) to determine the effectiveness and safety of decreasing the heparin dosage infused on the basis of activated partial thromboplastin time (APTT) prolongation reflecting both heparin and warfarin sodium effects. METHODS: We performed a randomized double-blind study evaluating a prescriptive approach to heparin administration in patients receiving heparin or heparin with warfarin. Thromboembolic and bleeding complications were objectively documented. RESULTS: Only 1% and 2% of patients had subtherapeutic heparin levels for 24 hours or more in the heparin and combined groups, respectively. Recurrent venous thromboembolism occurred infrequently in both groups (7%). Sixty-nine (69%) of 99 patients receiving combined therapy had supratherapeutic values, compared with 24 (24%) of 100 receiving heparin; bleeding complications occurred in 9% and 12%, respectively. CONCLUSIONS: Our findings demonstrate that no association exists between supratherapeutic APTT responses and bleeding, which is in direct contrast to the observed association between subtherapeutic APTT responses and recurrent venous thromboembolism. PMID- 1497393 TI - Severity of illness and resource use differences among white and black hospitalized elderly. AB - BACKGROUND: Disparities between races in access to health care services continue to exist. We examined differences in illness severity, charges, and length of stay between white and black hospitalized elderly. METHODS: The study sample was 1184 elderly patients. Data using the Computerized Severity Index were collected for admission, maximum throughout the stay, and discharge. RESULTS: Blacks were admitted significantly more severely ill than whites. At discharge, 96% were severity level 1. At each severity level, blacks had significantly shorter hospitalizations and lower charges. The differences were not explained by disease, surgery, age, sex, hospital, and payer. CONCLUSIONS: Admission severity disparities may exist because of patients' decisions to seek care or provider admitting practices. We need to study whether differences in severity-adjusted resource use are due to underutilization for blacks or overutilization for whites. PMID- 1497394 TI - Chronic fatigue syndrome criteria. A critique of the requirement for multiple physical complaints. AB - OBJECTIVE: The purpose of this study was to test the hypothesis that the patients with chronic fatigue who have the highest number of medically unexplained physical symptoms over their lifetime would also have the highest prevalence of current and lifetime affective and anxiety disorders, lifetime affective symptoms, and the most functional disability. A further goal was to use this information to modify the current case definition to better identify a subgroup of patients with chronic fatigue syndrome who are less likely to have psychiatric illness. DESIGN: Two hundred eighty-five consecutive patients with chronic fatigue were interviewed with the National Institute of Mental Health Diagnostic Interview Schedule and completed four self-rating questionnaires measuring psychologic distress, functional disability, and the tendency to amplify symptoms. Based on previously published data, patients were divided into four groups with a progressively higher number of lifetime medically unexplained physical symptoms. The prevalence of current and lifetime psychiatric disorders, lifetime psychologic symptoms, and extent of functional impairment was then compared in these four groups of patients. MAIN RESULTS: The prevalence of current and lifetime psychiatric diagnosis and lifetime depressive symptoms increased linearly with the number of lifetime physical symptoms that the patient experienced. The extent of impairment in activities of daily living and the tendency to amplify symptoms also increased linearly with the number of medically unexplained physical symptoms. CONCLUSION: The patients with the highest numbers of medically unexplained physical symptoms had extraordinarily high rates of current and lifetime psychiatric disorders. These data suggest that the current case definition for chronic fatigue syndrome inadvertently selects for patients with the highest prevalence of lifetime psychiatric diagnoses. A recommendation based on these results is to modify the case criteria for chronic fatigue syndrome to include patients with fatigue and few physical symptoms and to identify and consider excluding patients with high numbers of physical complaints. PMID- 1497395 TI - Angiographic patterns and severe coronary artery disease. Exercise test correlates. AB - In a Veterans Affairs Medical Center, we studied 607 male patients to determine whether patterns and severity of coronary artery disease could be predicted by means of standard clinical and exercise test data. We found significant differences in clinical, hemodynamic, and electrocardiographic measurements among patients with progressively increasing disease severity determined by angiography. Left main disease produced responses significantly different from those of three-vessel disease only when accompanied by a 70% or greater narrowing of the right coronary artery. Discriminant function analysis revealed that the maximum amount of horizontal or downsloping ST depression in exercise and/or recovery was the most powerful predictor of disease severity, with 2-mm ST depression yielding a sensitivity of 55% and a specificity of 80% for prediction of severe coronary artery disease (three-vessel disease plus left main disease). Patients with increasingly severe disease also demonstrated a greater frequency of abnormal hemodynamic responses to exercise. PMID- 1497396 TI - Gaps in the anion gap. AB - OBJECTIVE: To review limitations of the use of serum anion gap in clinical practice. DATA SOURCES: Original reports and reviews. STUDY SELECTION: Sources containing the most recent pertinent information. DATA SYNTHESIS: Theoretical and practical limitations beset the use of serum anion gap. Awareness of these limitations reduces but does not eliminate wrong diagnoses based on the anion gaps. CONCLUSIONS: Serum anion gap has a limited value in the differential diagnosis of acid-base disorders and can be misleading. PMID- 1497397 TI - Risk factors associated with complaints of insomnia in a general adult population. Influence of previous complaints of insomnia. AB - BACKGROUND: Insomnia is a common complaint both in the general population and also in physician's offices. However, risk factors for the development of insomnia complaints have not been completely identified. METHODS: To identify population characteristics associated with increased prevalence of insomnia complaints, we surveyed a large general adult population in 1984 through 1985. We evaluated the relationship among current complaints of initiating and maintaining sleep and obesity, snoring, concomitant health problems, socioeconomic status, and documented complaints of difficulty with insomnia 10 to 12 years previously. RESULTS: The strongest risk factor for complaints of initiating and maintaining sleep was previous complaints of insomnia (odds ratio, 3.5). In addition, female gender (odds ratio, 1.5), advancing age (odds ratio, 1.3), snoring (odds ratio, 1.3), and multiple types of concomitant health problems (odds ratios, 1.1 to 1.7) were all risk factors associated with an increased rate of complaints of initiating and maintaining sleep. CONCLUSION: Complaints of insomnia tend to be a persistent or recurrent problem over long periods of time. Female gender, advancing age, and concomitant health problems also are important risk factors. PMID- 1497398 TI - Pneumococcal endocarditis in Alaska natives. A population-based experience, 1978 through 1990. AB - BACKGROUND: Streptococcus pneumoniae is an uncommon cause of infective endocarditis (IE). We studied the presentation, microbiologic characteristics, and outcome of nine cases of S pneumoniae IE during a 12 1/2-year period in a population of 75,000 indigenous Alaska Natives (ANs), who have documented high rates of invasive pneumococcal disease. METHODS: Fifty-six cases of IE occurred in ANs statewide during 1978 through 1990. Medical records of all nine confirmed cases of S pneumoniae IE were reviewed. Incidence rates for S pneumoniae IE and all IE were calculated. RESULTS: Alaska Natives experience S pneumoniae IE as a fulminant illness, with acute aortic valve insufficiency (100%) frequently requiring emergent valve replacement, S pneumoniae meningitis (56%), and death (33%). No patient with S pneumoniae IE had known preexisting heart disease, and the most common underlying disease was alcoholism (56%). Pneumonia was diagnosed and embolic complications were suspected in 33%. All five S pneumoniae isolates examined were penicillin sensitive and were of serotypes included in the pneumococcal vaccine. Pneumococcal IE accounted for 15.8% of all IE diagnosed in ANs. Age- and sex-adjusted incidence rates for IE of all causes and S pneumoniae IE were 8.5 and 1.5 per 10(5) persons per year, respectively. During 1986 through 1988, 4.3% of AN adults diagnosed with S pneumoniae bacteremia developed S pneumoniae IE. CONCLUSIONS: Pneumococcal endocarditis in all but one AN case required emergent valve replacement and had a 33% mortality. The annual incidence rate of S pneumoniae IE in this population was five to 37 times higher than contemporary rates elsewhere. Increased efforts to prevent pneumococcal disease in ANs appear warranted. Clinicians everywhere should anticipate the possible development of S pneumoniae IE in adult patients with pneumococcal sepsis, especially with meningitis, even with previous vaccination and prompt adequate antimicrobial therapy. PMID- 1497399 TI - The prevalence of risk factors for venous thromboembolism among hospital patients. AB - BACKGROUND: This study provides an estimate of the prevalence of risk factors for venous thromboembolism among hospital patients. METHODS: The presence of risk factors for venous thromboembolism was determined from a retrospective review of the medical records of 1,000 randomly selected patients in 16 acute care hospitals in central Massachusetts. RESULTS: The most common risk factors for venous thromboembolism were age 40 years (59%) or more, obesity (28%), and major surgery (23%). The average number of risk factors increased with increasing age. One or more risk factors for venous thromboembolism were present in 78% of hospital patients, two or more in 48%, three or more in 19%, four or more in 6%, and five or more in 1%. CONCLUSION: Risk factors for venous thromboembolism are common among hospital patients, suggesting that prophylaxis should be widely employed. The cost-effectiveness and risk benefit of prophylaxis is well established in patients undergoing major surgery. Further studies are needed to confirm the benefit of prophylaxis in patients with nonsurgical risk factors for venous thromboembolism. PMID- 1497400 TI - Cost, uncertainty, and doctors' decisions. The case of thrombolytic therapy. AB - OBJECTIVE: To examine the prescribing patterns and predictors of physician choice in the selection of intravenous thrombolytic therapy for the treatment of acute myocardial infarction. DESIGN: Survey of a random sample of 250 California cardiologists between July 1989 and February 1990. RESULTS: The adjusted response rate was 66%. For a patient presenting within 30 minutes after the onset of an uncomplicated acute anterior-wall myocardial infarction, 98% of respondents reported that they would prescribe a thrombolytic agent, 79% chose tissue plasminogen activator, and 21% chose streptokinase. Users of tissue plasminogen activator were nine times more likely than streptokinase users to perceive tissue plasminogen activator as superior for early coronary artery recanalization, although most users of tissue plasminogen activator and streptokinase perceived no difference between the two agents for improvement in ejection fraction and mortality. Estimates of side effects did not distinguish the two groups. Users of streptokinase were eight times more likely to practice in a health maintenance organization than were users of tissue plasminogen. For a self-paying patient, 36% of users of tissue plasminogen activator said that they would switch to streptokinase, and 27% would switch for a patient insured by Medicaid. CONCLUSIONS: These results indicate that physicians place great emphasis on surrogate end points. Physicians vary in their willingness to use more expensive therapies over cheaper alternatives, even when their perceptions of the relative risks and benefits are similar. The patient's insurance status and the provider's practice setting may exert an important influence on doctors' clinical choices. PMID- 1497401 TI - Assessing medical interview performance. Effect of interns' gender and month of training. AB - Observation of history taking is commonly used to assess interviewing skills in medical internships, yet specific interviewing problems are infrequently documented. We evaluated videotaped recordings of 83 complete medical histories of new patients for content and questioning technique. Frequent deficiencies were found in history of medication compliance, gynecologic and psychiatric history, use of open questions, and mental status examination. The initial segments of 48 interviews were evaluated, and in 44% the patient was not allowed to complete their opening statement of concerns. Female physicians allowed fewer patients to finish their opening statement, and physicians at the end of the internship permitted the patients less time to express their concerns. Structured evaluation of complete histories reveals frequent interviewing problems as well as possible important effects of physician gender and length of training. PMID- 1497402 TI - Mortality in intensive care patients with respiratory disease. Is age important? AB - BACKGROUND: Age has been proposed as a criterion for health care rationing. However, the relationship of age and other prognostic factors to in-hospital mortality in older patients is unclear. The purpose of this study was to examine the effect of age on hospital mortality for patients admitted to the intensive care unit. METHODS: This historical prospective study examined 3050 admissions of patients aged 50 years and older with disease of the lower respiratory tract to intensive care units in 78 hospitals in the United States during an 18-month period (July 1987 through December 1988). The association of age with hospital mortality was examined by means of a multiple logistic regression model that included age, gender, primary discharge diagnosis, severity, and comorbid diseases. RESULTS: Variables significantly predictive of in-hospital mortality included age, severity of illness, diagnosis, and a history of chronic obstructive pulmonary disease. In contrast, gender, diabetes mellitus, congestive heart failure, angina, and stroke/transient ischemic attack were not significant predictors of mortality. Predicted mortalities varied from 0.7% to 40.7% in 50 year-old patients and from 5.5% to 78.6% in 90-year-old patients. CONCLUSIONS: Chronological age is independently associated with in-hospital mortality in patients with disease of the lower respiratory tract admitted to an intensive care unit. However, the clinical importance of this relationship is modulated by other variables, such as the primary diagnosis, the presence of comorbid conditions (chronic obstructive pulmonary disease), and the severity of the acute illness, such that use of age alone is not sufficient to predict hospital outcome. PMID- 1497403 TI - Presenting features and outcomes in patients undergoing temporal artery biopsy. A review of 98 patients. AB - BACKGROUND: Although temporal arteritis is a well-recognized syndrome, controversy still exists regarding the optimal approach to diagnosis and treatment of this condition. We undertook this review to further define the spectrum of presenting features and outcomes of patients undergoing temporal artery biopsy. METHODS: We reviewed the records of all patients undergoing temporal artery biopsy over a 5-year period. Presenting features were compared in biopsy-positive and biopsy-negative patients. In patients with positive biopsy specimens, treatment regimens, disease, treatment-related morbidity, and outcomes were recorded. Alternative diagnoses and therapy were reviewed in biopsy-negative patients. RESULTS: Of 98 patients, 30 had positive and 68 had negative biopsy specimens. Biopsy-positive patients had an increased incidence of headache (93% vs 62%), jaw claudication (50% vs 18%), and prior polymyalgia rheumatica (23% vs 3%), but the sensitivity and specificity of these indicators were relatively low. Other clinical and laboratory parameters, including prior steroids and erythrocyte sedimentation rate, were similar between the two groups. In 30 patients with positive biopsy specimens, response to initial high-dose steroid was excellent. Serious manifestations after initial treatment were not seen, but mild flares were common after 1 year of therapy. Steroid-related morbidity was common, and steroids were seldom discontinued (0/22 patients at 1 year, 6/19 patients at 2 years, 5/11 patients at 3 years). In 68 patients with negative biopsy specimens, alternative diagnoses included neurologic diseases (15 patients), "pure" polymyalgia rheumatica (14 patients), and other inflammatory rheumatologic diseases (10 patients). Fourteen patients with negative biopsy specimens were treated for temporal arteritis, and were similar to biopsy positive patients. CONCLUSIONS: Temporal arteritis remains a challenging condition to diagnose and to treat. Presenting features are seldom helpful in predicting biopsy results. Initial treatment is effective but frequently toxic. Although late disease-related complications are rare, most patients continue to take long-term low-dose steroid therapy. PMID- 1497404 TI - Cough and ACE inhibitors. AB - To assess the prevalence of cough as a side effect of angiotensin-converting enzyme inhibitor antihypertensive therapy, we reviewed 300 consecutive patient charts from a private practice and 200 consecutive patient charts from a university-based referral center for hypertension. Incidence of definite angiotensin-converting enzyme inhibitor-induced cough in the private practice was 25% and in the university practice, 7%, with an additional 6% of university practice patients reporting a possible angiotensin-converting enzyme-inhibitor induced cough. This incidence is considerably greater than listed in the Physicians' Desk Reference. Reasons for the variability in incidence as reported in the literature are explored. Clinicians must be aware of this potentially disturbing side effect of angiotensin-converting enzyme inhibitors to avoid expensive and unnecessary diagnostic evaluations. PMID- 1497405 TI - Clostridium difficile diarrhea induced by cancer chemotherapy. AB - Four patients had diarrhea due to Clostridium difficile after receiving chemotherapy for cancer. None of the patients had received antibiotics for at least 4 weeks before the onset of diarrhea. At the time of admission of any of these four patients no outbreak of diarrhea was noted on the ward. Each patient was admitted with the acute onset of diarrhea after receiving chemotherapy, at different times of the year. Diarrhea was clinically important and was associated with dehydration, toxemia, and blood in the stool in all cases. Diagnosis of C difficile was confirmed by endoscopic examination, positive biopsy specimen, and positive test for toxin in the stool. All patients recovered after undergoing specific treatment. Drugs not believed to carry serious risk to the bowel mucosa may facilitate proliferation of C difficile. Patients with severe diarrhea after receiving chemotherapy, particularly those with blood in the stool, should be promptly tested for C difficile even in the absence of a history of antibiotic administration. Early and specific treatment can prevent additional morbidity and reduce cost of care. PMID- 1497406 TI - Can vitamin D deficiency produce an unusual pain syndrome? PMID- 1497407 TI - Life-style changes and lipid lowering. PMID- 1497408 TI - Sublingual captopril and nifedipine in immediate treatment of hypertensive emergencies. PMID- 1497409 TI - Association between porphyria cutanea tarda and human immunodeficiency virus infection. PMID- 1497410 TI - The prevention of tetanus. PMID- 1497411 TI - Tetanus in the elderly. PMID- 1497412 TI - The continuum of hyperthermic syndromes with impaired dopaminergic activity. PMID- 1497413 TI - Relationship of Christopher Columbus to spread of rheumatoid arthritis. PMID- 1497414 TI - [Validation of axillary temperature measurement as a biorhythm marker. Study of the sex variable]. AB - This paper analyses the relationship between oral and axillary temperatures in the waking part of the day, and verify the existence of sex differences within both parameters. We selected 20 healthy subjects (10 men and 10 women) aged 22 to 30, controlling environmental and subject variables. The women's group does show greater thermic values for axillary temperature (8 of the 13 recordings). There was a highly correlation between sex groups (r = 0.854, p less than 0.001), axillary temperature rhythms between sexes are coupled and any differences are only of degree. For oral temperature the women's group showed higher values in 3 recordings (15.00, 18.00 and 21.00), and there was no correlation between men and women throughout the day. These results evidence sex differences in rhythmic patterns of oral temperature. Correlations between temperatures were highly positive for the whole sample, men and women. Our study presents empirical data on the validity of using axillary temperature as alternative measurement of body temperature. We expect the use of axillary temperature to be increasingly employed in chronobiological field studies. PMID- 1497415 TI - [Acetylcholinesterase activity during the cortical development of the cat brain]. AB - Acetylcholinesterase (AChe) hydrolyses acetylcholine to choline and acetate, thereby inactivating the neurotransmitter. However, the possible non-cholinergic function of this enzyme has been recently suggested. In the present work, changes in AChe activity during the postnatal development of the cat brain are described, in order to show if the enzyme could play a part in the maturing processes of the CNS. The study was performed in the frontal and parietal cortices, area 17 and areas 18 and 19 as a whole in the 15 and 30 days postnatal stages. Significant increases with age were observed in all the brain areas under study. It is suggested that this enzyme activity play a part in the maturation of the cat brain cortices, possibly in the cholinergic development and/or as a cell growth regulatory factor. PMID- 1497416 TI - [Subtypes of muscarinic acetylcholine receptor following the experimental denervation of the cholinergic pathway ascending to the neocortex]. AB - BACKGROUND: Use of an experimentally induced neurotoxic lesion of the ascending cholinergic pathway to the neocortex, in rat brain, to study the postulated selective loss of muscarinic receptor subtypes (mAChR) presynaptically located (autoreceptors). METHODS: Stereotaxic lesion of n. basalis magnocellularis was induced by 25 nmol Ibotenic acid injection in the right brain hemisphere of adult, male, Wistar rats. The contralateral hemisphere served as control. Antagonist (quinuclidinyl-benzilate) and agonist (carbachol) specific binding to mAChR receptors at equilibrium was studied 7 days post-lesion on a P2 fraction of brain cortex homogenate. Displacement of antagonist binding by carbachol was analyzed by "one-point" and "two-point" model fits. RESULTS: Muscarinic receptors on the control hemisphere show no sign of lesion related changes as compared to data for intact rat brain: Bmax = 0.896 pmol/mg protein and Kd = 0.25 nM. In the lesioned hemisphere a -10.3% loss of antagonist binding (not statistically significant) was observed, with an increase in receptor affinity. Heterogeneity of agonist binding was found; receptor subtype analysis showed that the proportion M2/M1 was unchanged but an increase in carbachol (M2 selective affinity) did appeared. CONCLUSIONS: We found no evidence of a selective presynaptic localization of muscarinic receptor sub-types on terminals of the cholinergic ascending pathway to the neocortex. A receptor loss related to the intensity of the neurotoxic lesion is suggested as well as the presence of regulative mechanisms (hypersensitivity) for receptors. PMID- 1497417 TI - [Brainstem lesion in multiple sclerosis, blink reflex, and brainstem auditory evoked potentials]. AB - Blink reflex (BR) and brainstem auditory evoked potentials (BAEP) were recorded from 168 patients with several diagnostic categories of multiple sclerosis, from which 98 complained brainstem symptoms (BSS+). From the whole group, the BR showed a higher degree of abnormality (45.75%) than BAEP (27.95). This range increased in the group BSS+ (52.15% for the BR and 34.9% for the BAEP) and even more when sings or symptoms of brainstem were present at the time of exploration (BSS+P) 60.4% for the BR and 41.3% for BAEP. Among patients who never complained brainstem symptoms, the BR disclosed a subclinical lesion in the 33.3% and the BAEP in the 16.9%. The combination of BR and BAEP were more useful than an isolated test. The localization of the lesion both clinically and in the BR were mostly on the pons. Light correlation between the presence of isolated or multiple symptoms and the disorder in the BR were present. Facial myokymia and internuclear ophthalmoplegia were most often associated with disorder in the BR, in both, the commonest localization was on the pons, and in the former about the motor nucleus of the facial nerve. PMID- 1497419 TI - [Molecular biology and pathology of cystic fibrosis. Two years after cloning of the gene]. PMID- 1497418 TI - [Modulatory capability of the somatosensory afferents through acupuncture reflexotherapy]. AB - This paper concerns the influence of the acupuncture on the somatic afferent volley. As the main used points in experimental acupuncture, we stimulated 4GI and 7H. The results confirm the modulatory influence of the acupuncture on the somesthetic afference and, also, its different mode of action related with the nature of the point stimulated. PMID- 1497420 TI - [Gastroesophageal reflux in daily practice]. PMID- 1497421 TI - [Growth cartilage and abnormal growth]. PMID- 1497422 TI - [Treatment of adenosine deaminase deficiency with adenosine deaminase combined with polyethylene glycol]. AB - Adenosine deaminase (ADA) deficiency is one the causes of severe combined immunodeficiency syndrome. Treatment was, until now, based on bone marrow transplantation. HLA identical bone marrow transplantation yields excellent results while those of HLA haploidentical bone marrow transplantation are not so good. A new therapeutic approach was developed recently, consisting of the intramuscular infusion of ADA enzyme covalently linked to polyethylene glycol (PEG-ADA). We report the results of this treatment in a 14 month-old child presenting with a partial form of ADA deficiency revealed by an opportunistic infection. This treatment corrected the immunodeficiency and the biochemical abnormalities as well. PEG-ADA infusions were well tolerated. The onset of an immunization against the ADA enzyme led to a drop in immunologic functions, which could be partially overcome by more frequent (biweekly) administration of the product. After a 18 month-follow-up the child is doing well, living normally at home. PEG-ADA represents a possible alternative for children presenting with ADA deficiency without any available HLA identical donor. PMID- 1497423 TI - [Value of MRI in various forms of idiopathic growth hormone deficiency]. AB - Magnetic resonance imaging (MRI) of the sellar and juxta sellar area was performed in 40 children with idiopathic hypopituitarism. MRI was normal in the 17 patients with partial growth hormone (GH) deficiency and in the 5 patients with GH neurosecretory dysfunction. Among the 18 patients with complete GH deficiency, the 10 with pituitary stalk transection presented more often with perinatal abnormalities, had the most severe GH deficiencies and more frequently multiple hormone deficiencies, in particular TSH deficiency. Pituitary gland size studies showed that the small size of the residual glandular tissue was responsible for these particularities. If MRI is of no great interest for functional GH deficiency, in half of the primary complete GH deficiencies, it enables to visualize a pituitary stalk transection with regeneration of neurohypophysis. PMID- 1497424 TI - [Hemodynamic and renal adaptation of newborn infants of hypertensive mothers treated with acebutolol]. AB - A prospective study of the hemodynamic and renal changes was undertaken in 11 neonates whose mothers were treated with acebutolol for hypertension during pregnancy, compared with a control group of 11 infants born to normotensive mothers. Monitoring of the cardio-respiratory system was performed for a period of 4 days. Renal function was studied during 2 periods (12-36, 60-84 hours of life). Hemodynamic failure was observed in 5 of 11 children from treated mothers. The data concerning the renal function of treated group showed: 1) a diuresis significantly lower during the first period (p less than 0.05); 2) the absence of significant rise in the glomerular filtration rates during the second period; 3) a lower sodium balance during the 1st and 2nd periods (p less than 0.02 and p less than 0.05), a lower calcium balance during the 1st period (p less than 0.01). No relationship was found between the renal changes and the hemodynamic disturbances. The direct effect of the drug on the glomerular and tubular functions and/or the renal arteriolar vasomotricity could explain these changes in the renal function in the newborns prenatally exposed to acebutolol. PMID- 1497425 TI - [Study of serum kinetics of vancomycin during the "antibiotic-lock" technique]. AB - The serum kinetics of vancomycin was studied in two patients aged 3 and 15 years during antibiotic therapy for catheter related sepsis associated with Staphylococcus epidermidis. Vancomycin was administered, simultaneously, by parenteral conventional doses (30 mg/kg/day div q 8 h) and using the antibiotic lock technique in the infected catheter at a high concentration (150 mg/ml) during one hour, 3 hours after each infusion. Pharmacokinetics data did not show any significant change in the serum kinetics of the antibiotic. The results suggest that delivering a high concentration of vancomycin in the infected catheter using the lock technique may be useful to sterilize infected catheter without toxic effect. PMID- 1497426 TI - [Insulin resistant diabetes, acanthosis nigricans and Bartter's syndrome, a fortuitous association?]. AB - The authors have followed during 10 years a girl with Bartter's syndrome who developed severe insulin resistance with acanthosis nigricans. In this rare association, hypokalemia and renal failure did not appear to be relevant factors triggering the onset of diabetes. The therapeutic difficulties in this case have still not been resolved. PMID- 1497427 TI - [Duodenal atresia with bifid termination of the common bile duct]. AB - A new case of duodenal atresia with gas below the obstruction is reported. This apparently contradictory feature is due to a bifid termination of the common bile duct in the duodenum, air by-passing the atretic area. The anomaly was proven by operative cholangiography. PMID- 1497428 TI - [Striatal involvement with abnormal movements in hemolytic-uremic syndrome]. AB - Two children with hemolytic-uremic syndrome (HUS) presented with alteration of consciousness and severe abnormal movements related to striatal involvement. They required dialysis and controlled ventilation. Steady improvement in neurologic function was seen during the following weeks, and abnormal movements disappeared. It is suggested that the pathogenesis of neurological dysfunction in these two children was related to intracerebral microangiopathy, because neither systemic arterial hypertension, nor metabolic disturbances were present. This hypothesis is supported by the cerebral blood flow study in one patient. Neuropathologic studies of patients with HUS who presented with CNS symptoms showed vascular thromboses within the CNS: CT scan demonstrated multiple small areas of infarction, particularly in the basal ganglia. The prognosis of HUS is generally worsened in case of severe CNS involvement, but abnormal movements may disappear without sequelae. PMID- 1497429 TI - [Cardiac tamponade secondary to umbilical venous catheterization accident in a premature infant]. AB - BACKGROUND: Cardiac tamponade is a rare and sometimes severe complication of umbilical venous catheterization. CASE REPORT: A premature newborn (gestational age: 30 weeks, birth weight: 1,215 g) required assisted ventilation and umbilical venous catheterization for respiratory distress. Subsequent chest X-ray showed the ascending tip of the catheter lying in the left atrium, inside the auricle. At the age of 16 hours, the infant presented with episodes of bradycardia. Despite a second endotracheal intubation, a sudden vascular collapse necessitated cardiac massage plus sodium bicarbonate and epinephrine. An ultrasound examination was performed because of the persistence of the vascular collapse; it showed a clear echo-free space between the epicardium and pericardium, suggesting pericardial effusion. The patient responded dramatically to pericardial aspiration, providing hemorrhagic fluid containing 20 g per liter glucose. DISCUSSION: Cardiac tamponade probably occurred in this patient as a result of perforation of the atrial wall. Ultrasonography showed no local thrombus, but confirmed the cardiac compression by pericardial fluid and the localization of the tip of catheter in contact with the atrial wall. This case led us to review the mechanical complications of umbilical venous and/or percutaneous catheterization and the rules for their use. CONCLUSION: This complication must be suspected in all patients having a central venous catheter that present with vascular collapse. PMID- 1497430 TI - [Anti-Haemophilus b vaccine]. PMID- 1497432 TI - [Autumn days. Paris, October 1991]. PMID- 1497431 TI - [Role of glucocorticoids in the treatment of bacterial meningitis in children]. PMID- 1497433 TI - [Autoimmune neutropenia and parvovirus B19 infection]. PMID- 1497434 TI - [Incidence of mycoplasmal colonization in neonatal care unit]. PMID- 1497435 TI - [A combination of two antipyretic agents, is it adequate for the treatment of hyperthermia in pediatric patients?]. PMID- 1497436 TI - [Vertex spikes in newborn infants with acute cerebral anoxia]. PMID- 1497437 TI - [Currarino's syndrome?]. PMID- 1497438 TI - CLIA '88. More misguided regulation, or a promise of quality? PMID- 1497439 TI - Literature review of research related to the Clinical Laboratory Improvement Amendments of 1988. AB - In conjunction with a 1990 Report to Congress on the studies required by the Clinical Laboratory Improvement Amendments of 1988 (CLIA '88), the Centers for Disease Control, Atlanta, Ga, prepared a summary of the existing scientific literature related to the five studies listed in Section 4 of the Act. Over 800 articles were identified that, by title, seemed to deal with subjects that have been assumed to be associated with the quality of clinical laboratory testing. Although our search was not exhaustive, we believe that the articles included in our search are representative of the scientific evidence that exists. Most of the articles collected in our initial search were later eliminated from additional review because they were determined to be evaluations of laboratory analytic methods, contained only anecdotal evidence, were primarily descriptions of methods or programs, or were opinion articles without specific scientific data to support the opinions. This review reports the conclusions drawn by the research investigators of the 90 referenced articles; it does not analyze each article to assess the scientific validity of the research nor does it critique each article that is included. The review points to the need for additional research to answer questions raised by CLIA '88. PMID- 1497440 TI - Quantification of errors in laboratory reports. A quality improvement study of the College of American Pathologists' Q-Probes program. AB - Over a 3-month period, 61,496 errors were detected in clinical laboratory reports by 631 participants in the College of American Pathologists' 1990 Q-Probes program. Each error detected was defined as an opportunity for improvement. Almost 4% of the detected errors were attributed to nonlaboratory personnel and approximately 4% (A errors) had a major impact on patient care. Rates of B (serious errors, but unlikely to affect patient care) and C errors (minor clerical errors) were approximately equal. When expressed in terms of measures of laboratory work loads, four of six measures of mean errors were lowest in blood banking, intermediate in chemistry and microbiology, and highest in hematology. Thirteen percent of participants did not have an error detection system in place. We conclude that many errors go undetected, and we recommend that an effective system for error detection in patient reports should be employed in all laboratories. PMID- 1497441 TI - Determination and validation of reference intervals. AB - A brief overview of the concept of the reference interval and its application in medical practice is presented. The populations from whom it is possible to derive reference intervals are discussed. Procedures used to develop reference intervals from both a selected healthy population and from hospitalized patients are discussed, and the influence of statistical method on presented reference intervals is reviewed. However, the weakness of using a reference interval derived from a population of individuals to facilitate interpretation of test results is illustrated in relationship to the variability of test results within an individual. In spite of the efforts that are made within the clinical laboratory through development of reference intervals to provide maximum guidance to clinicians to facilitate their proper interpretation of test values in patients, it is apparent that much of the carefully derived scientific information is ignored in actual practice. PMID- 1497442 TI - Determination of reference intervals in the clinical laboratory using the proposed guideline National Committee for Clinical Laboratory Standards C28-P. AB - The Subcommittee on Reference Intervals of the National Committee for Clinical Laboratory Standards (NCCLS) has recently completed a proposed guideline, NCCLS Document C28-P, entitled "How to Define, Determine, and Utilize Reference Intervals in the Clinical Laboratory." This guideline document is an attempt to combine a concise set of procedures and recommendations, largely taken from the original literature, to form a standard, uniform, and reasonable protocol for determining population-based reference intervals. The intent of the guideline is to set forth the minimum requirements for the determination of a reliable and clinically useful reference interval. The subcommittee hopes the document will set a standard that upgrades the quality of reference intervals to a level worthy of their use in clinical medicine. PMID- 1497443 TI - The concept of establishing vs verifying analytic claims in method evaluations. AB - The establishment of analytic claims occurs during the method development stage. For commercial methods, the thorough characterization of analytic performance is the responsibility of the manufacturer. The manufacturer establishes performance claims with a high degree of certainty by utilizing statistically sound experimental protocols with sufficient degrees of freedom. The manufacturer should establish performance claims that state the expected performance of the method for the intended spectrum of patients and laboratory environment. The verification of analytic claims occurs by the end-user of the method. The end user should not have to necessarily repeat the extensive protocol testing of the manufacturer that was used to establish the performance claims. The goals of the method verification study are not to establish analytic performance or to determine if the analytic performance is clinically acceptable, but, simply, to confirm or verify the stated established performance claims of the manufacturer. This implies an abbreviated method evaluation with statistical confirmation that analytic performance is acceptable. Analytic parameters that should be verified are imprecision, inaccuracy (bias), and linearity including analytic sensitivity. Reference ranges should be determined if the patient population is unique, or if the reference range of the analyte is relatively new or unstudied. Principles of method evaluation are discussed. PMID- 1497444 TI - Establishing and maintaining performance claims. A manufacturer's viewpoint. AB - Performance claims are the vehicle by which a manufacturer communicates the analytic capabilities of its methods to laboratory users and to regulatory agencies. Claims describe the expected performance of an analytic system. To be useful, claims must be meaningful, achievable, and verifiable. To ensure consistent interpretation, they must be stated in clear, unambiguous terms. There are no specific guidelines for stating claims. Consequently, comparing the performance of one system to another is difficult. Claims fall into three categories: clinical utility, analytical performance, and boundary conditions. This article focuses on the three basic analytical performance characteristics, precision, accuracy, and specificity, and describes how they are established, validated, maintained, and monitored by manufacturers and how they can be verified by end users. Precision claims describe the inherent variability of the system. They differ in the components of variance included, ranging from the short-term variables within a single run to the long-term variables experienced over time, such as lot changes, calibrations, instrument drift, and environmental fluctuations. Precision may be stated either as typical user experience or as the minimum performance expected. Accuracy claims describe the degree to which the results will approximate the true values. They are more difficult to establish and verify, given the lack of objective standards for many analytes. For this reason, few manufacturers make true accuracy claims, relying instead on comparisons with other marketed methods. A notable exception is cholesterol, for which a model reference system has been established to help laboratories ensure accuracy. External proficiency testing is handicapped by matrix effects from imperfect survey fluids. Specificity claims describe the method's freedom from interference and cross-reactivity. They are based on screening tests by the manufacturer, augmented by feedback from users. There are no agreed-on criteria for what constitutes clinically significant interference, and no consistent approach for disclosing interference information. The National Committee for Clinical Laboratory Standards, Villanova, Pa, is beginning to develop guidelines to promote greater consistency in performance claim statements. PMID- 1497445 TI - Estimating total analytical error and its sources. Techniques to improve method evaluation. AB - The process of method evaluation starts with identifying goals either to demonstrate the clinical validity of an assay or to identify assay error sources that require improvement. Taguchi's idea of continual quality improvement vs the notion of meeting or failing specification has been applied to clinical chemistry. In this article, I propose a model of assay performance that includes the terms random interferences and protocol-specific biases (a series of systematic errors). I explain these terms, as well as the consequences of failing to consider them. To validate an assay clinically, I recommend direct estimation of total analytical error from a method comparison. To identify assay error sources that require improvement, I recommend a multifactor protocol (in addition to a method comparison). Individual error sources are related to total analytical error with the use of an error propagation technique. Much of the proposed data analysis techniques are straightforward but not routinely practiced. I demonstrate principles with the use of a cholesterol assay. PMID- 1497446 TI - Foundations for validation of quantitative analytical methods in the clinical laboratory. AB - This article explores federal requirements for validation of analytical methods and available resources. We focus on the contributions of the National Committee for Clinical Laboratory Standards to the problems of method validation. Illustrations are selected from the Committee's EP5-T Evaluation of Precision, EP10-T Preliminary Evaluation of Clinical Chemistry Methods, EP11 Uniformity of Claims, and the National Reference System for the Clinical Laboratory. We also include a list of applicable national and international organizations. Calcium assay by atomic absorption spectrometry using an imprecise diluter illustrates the application of the evaluation protocols as a method validation tool. PMID- 1497447 TI - College of American pathologists experience with the linearity surveys, 1987 1991. AB - The Instrumentation Resource Committee has offered a survey since 1988 to perform and evaluate linearity. The survey uses a serum-based material and satisfies federal regulations that require linearity evaluations in the clinical laboratory. Both statistical and empirical methods to determine linearity were developed for the survey. Participant results have shown a high rate of nonlinear methods that may be due to our inability to accurately determine linearity or may reflect the true state of clinical assays. The survey shortcomings and future projects are discussed. PMID- 1497448 TI - Alternative statistical techniques to evaluate linearity. AB - With the increase in demand for linearity assessment, a wide variety of analysis techniques have been advocated. There is no consensus on optimal techniques. This article reviews different approaches that have been advocated by the College of American Pathologists, by the National Committee for Clinical Laboratory Standards, and by manufacturers of diagnostic methods and controls. This is not a review of all statistical techniques proposed for linearity assessment. I discuss four basic categories of methods, with the first and simplest being visual review. The second general approach includes the conventional statistical techniques based on least-squares regression; this includes an equation for the line and statistical tests for linearity and for curvature. The third general approach involves comparison of slopes for line segments, or "deltas." This approximates the visual assessment of linearity. The fourth approach involves comparing observed and expected values, with some allowance for differences. Comparisons can be made for observed single results, means of replicates, or components of variance. Allowances for error can be internal goals or goals that are recommended for clinical usefulness. Each approach has strengths in different aspects of linearity assessment, including intuitive appeal, statistical rigor, and objectivity. Similarly, each approach has limitations that are not always obvious. PMID- 1497449 TI - Linearity and calibration. A clinical laboratory perspective. AB - This article discusses the relationship of calibration and linearity using the example of glutaraldehyde assayed by high-performance liquid chromatography. Assuming adequate precision and a lack of interference, the relationship of calibration to a method's linear range becomes all important to achieving quality analytical results. Linearity is an objective description of the relationship between a quantitative method's final answer and true analyte concentration. Calibration brings this relationship into correspondence with calibrator concentration. The reportable range is that range within which a specified method produces results within defined allowable error without resorting to dilution of the specimen. The reportable range assumes a linear relationship between true analyte concentration and analytical results. PMID- 1497450 TI - Correspondence of linearity evaluations to the performance of clinical chemistry instrument and reagent systems. AB - The importance of demonstrating linearity for a clinical chemistry analytical system has caused considerable debate. Disagreement about the way linearity is demonstrated has led to some misunderstanding about just what linearity means to the analytical goals. In many cases where linearity is evaluated by statistical means, the outcome will indicate a nonlinear condition. A subsequent graph plot of the same data usually produces a line that is virtually straight. Confusion over which linearity evaluation outcome to accept creates a lack of confidence in either approach owing to the sometimes obvious disagreement between the two outcomes and the ill-defined impact linearity has on analytical error or clinical usefulness. Models of analytical performance can be constructed in such a way that the paradox of conflicting linearity evaluations can be examined through their effects on the analytical goals. PMID- 1497451 TI - Assuring analytical quality through process planning and quality control. AB - United States governmental regulations describe quality assurance as a system in which quality control (QC) and proficiency testing are to be used to substantiate that routine tests conform to specified performance criteria. Careful planning of analytical processes is necessary to guarantee that routine tests will achieve the analytical performance defined by the Health Care Financing Administration proficiency testing criteria. These proficiency testing criteria are analytical "total error" requirements that need to be translated into operational process specifications for the allowable imprecision, allowable inaccuracy, and the QC procedure (decision rules, number of control measurements) necessary to provide a known or specified level of analytical quality assurance. The level of assurance will depend on the QC procedure's probability for detecting critical sized errors that would cause the quality requirement to be exceeded. Analytical quality can be guaranteed by applying statistical QC to verify, with a specified probability, that a desired quality requirement is actually achieved in routine laboratory testing. Analytical quality assurance, applied in this way, can be a quantitative approach for guaranteeing quality through process planning and QC. PMID- 1497452 TI - Health Care Financing Administration's new proficiency testing rules. Use of a statistical approach to predict long-term performance using the categories 'successful,' 'probation,' and 'suspended'. AB - Under the Clinical Laboratory Improvement Act of 1967 (CLIA-67) and the Medicare Act, the Health Care Financing Administration's proficiency testing rules apply uniformly to all hospital and reference laboratories. We examined the relationship between internal laboratory performance as characterized by bias and coefficient of variation and proficiency testing performance, categorized as "successful," "probation," and "suspended." Under the March 14, 1990, final rule, a laboratory with suspended testing for even one analyte may be required to cease testing in the entire subspecialty, eg, routine chemistry, unless it ceases testing for that analyte. Analyzing this regimen as a Markov process, we obtained the steady-state solution for performance for one to 27 analytes. While 1.1% of laboratories testing for five analytes with internal or day-to-day coefficients of variation at 50% of the CLIA-67 proficiency testing limit would be suspended, 19.5% of laboratories having biases of 50% and coefficients of variation of 33% would be suspended. We conclude that after eight events, there will be an unacceptably high rate of suspensions. PMID- 1497453 TI - Selection of measurement and control procedures to satisfy the Health Care Financing Administration requirements and provide cost-effective operation. AB - The basic principles of method evaluation and quality control system design have been extensively studied and described. However, the interaction among the various independent variables comprising the complete analytical system is not so well known. In this article, a model of a generalized analytical system is presented and the nature of the interaction among analytical method parameters and quality control system parameters is explored. Implications of recent Health Care Financing Administration regulations for allowable total error are also discussed. PMID- 1497454 TI - Achieving the Health Care Financing Administration limits by quality improvement and quality control. A real-world example. AB - With the enactment of the Clinical Laboratory Improvement Amendments of 1988 (CLIA 88), the federal government is now using proficiency testing as the primary indicator of laboratory quality. Laboratories with proficiency test failures are now at risk of a variety of harsh penalties including large monetary fines and suspension of operations. To minimize the risk of failed proficiency testing, we initiated a continuous quality improvement program in our general chemistry laboratory in conjunction with the use of a new survey-validated quality control product. This article describes the quality improvement program and our success in reducing the long-term random error in general chemistry. Despite our improvement program, significant analytical errors (greater than 30% of the CLIA limits) still exist in analytes measured by our chemistry analyzer. These errors are present in nearly the same analytes measured by other common chemistry analyzers indicating the need for improvement in their design and manufacture. PMID- 1497455 TI - The use of control charts in the clinical laboratory. 1950. PMID- 1497456 TI - 'Carcinosarcoma' of the bladder. PMID- 1497457 TI - Inappropriate frozen sections. PMID- 1497459 TI - Piecing together the quality puzzle. Laboratory medicine's role in medical practice. PMID- 1497458 TI - Kaposi's sarcoma and lymphoid neoplasia in the same lesion. PMID- 1497460 TI - Favorable vs unfavorable histologic appearance. The lexicon of pathologic grading of solid malignant neoplasms in children. PMID- 1497461 TI - Laboratory staff qualifications and accuracy of proficiency test results. A national study. AB - In the last quarter of 1988, laboratories from across the country that participated in the College of American Pathologists (Northbrook, Ill) proficiency testing program were asked to complete a questionnaire describing their staffing pattern and submit it with their test results. Laboratories were then divided into two groups, those employing 100% American Society of Clinical Pathologists (Chicago, Ill) certified technologists and those employing 0% American Society of Clinical Pathologists certified technologists. The nonparametric Wilcoxon significance test was used to determine differences in accuracy of test results for laboratories in each group. Significant differences were found for the basic laboratory survey, comprehensive diagnostic immunology, comprehensive blood banking, comprehensive hematology, and comprehensive chemistry. chi 2 Analysis revealed that laboratories employing 100% American Society of Clinical Pathologists certified technologists had a significantly higher probability of achieving 80% accuracy across all surveys. These results present a strong argument that staffing with qualified technologists contributes to maximizing the quality of laboratory services offered to the public. PMID- 1497462 TI - Within-subject biological variation of hematological quantities and analytical goals. AB - For several common hematological quantities, the within-subject biological variation during a 1-year period was estimated in a group of 39 apparently healthy volunteers: 19 women and 20 men. All measurements were performed with a hematological analyzer (Toa E-5000, Toa Medical Electronics, Kobe, Japan). The means of the within-subject biological coefficients of variation, separated by sex when significant difference was shown, were as follows: 2.8% for hemoglobin concentration; 3.0% for erythrocyte concentration; 2.9% for erythrocyte volume fraction; 1.1% for mean erythrocyte volume; 1.9% for arbitrary SD of erythrocyte volume; 1.6% for mean erythrocyte hemoglobin concentration; 1.3% for mean erythrocyte hemoglobin; 10.8% in men and 15.7% in women for leukocyte concentration; and 6.7% in men and 8.6% in women for platelet concentration. The desirable between-day imprecisions for the measurement of each quantity were established as one half of the average of within-subject biological variation. PMID- 1497463 TI - Detection of beta-endorphin in human blood. A study of performance characteristics of different radiometric systems. AB - beta-Endorphin, an opioid peptide that contains 31-amino acids derived from proopiomelanocortin, has been implicated in a variety of disorders. To understand its role in pathophysiological states, its levels have been determined in body fluids, particularly in serum or plasma, with the use of commercially available radiometric assay kits. Because the circulating levels of this endogenous opioid peptide are small and antibodies can cross-react with chemically related peptides to different degrees and give rise to faulty interpretation of the data, the performance characteristics of the available radioimmunoassay kits for beta endorphin from the Immuno Nuclear Corporation, Stillwater, Minn, the New England Nuclear Corporation, Boston, Mass, and the Nichols Institute, San Juan Capistrano, Calif, were evaluated. In overall performance, the Nichols kit was found to be the most reliable in this laboratory, even though the sensitivity of the Immuno Nuclear kit was better at lower concentrations of beta-endorphin. Serum was better than plasma in terms of recovery of beta-endorphin. When collected on ice, no significant loss in beta-endorphin immunoreactivity was observed at 1 hour. The use of edetic acid (EDTA), siliconized edetic acid, and aprotinin (Trasylol)-added siliconized edetic acid tubes was not helpful in improving the performance of the assay. The optimal condition to collect the specimen was to use glass tubes, place the glass tubes on ice immediately, separate the serum, and freeze the sample within 1 hour of collection. PMID- 1497464 TI - Very high values of serum high-density lipoprotein cholesterol. AB - Little is known about individuals who have very high values of serum high-density lipoprotein cholesterol (HDL-C) with the exception of those who have very rare genetic conditions, eg, familial hyperalphalipoproteinemia or hypobetalipoproteinemia. During a period of 60 months of testing for HDL-C, we found 46 individuals (of whom 43 were women) who had an HDL-C level equal to or higher than 2.58 mmol/L (greater than or equal to 100 mg/dL) (range, 2.58 to 6.15 mmol/L [100 to 238 mg/dL]). Sixteen of these individuals were treated with estrogens or ranitidine or were alcoholic, and several had evidence of coronary heart disease. We conclude that very high values of HDL-C can be found in the general population mostly in women, and this is often related to environmental causes, eg, the use of H2-blockers, estrogens, and alcohol. The finding of very elevated HDL-C levels in serum is probably not always due to a genetic condition and does not always signify absence of coronary heart disease and increased life expectancy. PMID- 1497465 TI - Activated partial thromboplastin time reagent sensitivity to the presence of the lupus anticoagulant. AB - The lupus anticoagulant (LA) is an acquired abnormality that is associated with a prolonged activated partial thromboplastin time (aPTT). It is one of the most frequent coagulation abnormalities seen in the routine clinical laboratory. The sensitivity of various commercial aPTT reagents varies in their ability to detect the LA. We undertook this evaluation by using a single coagulation instrument to determine the sensitivity of five different commercial aPTT reagents to the presence of the LA. We evaluated 23 patients with known LA using five different reagents, two of which were marketed as having enhanced LA sensitivity. All samples and testing were performed under the same conditions in a timely manner. Based on these data, essentially all of the commercial reagents that were tested could detect patients with known LA by at least minimally prolonging the aPTT. Some reagents were slightly better than others in their ability to detect the LA. For most hospitals, the detection of the LA is not the highest priority for the use of the aPTT assay. In most cases, heparin anticoagulation monitoring is the most common use of the aPTT assay. Since all five reagents are sensitive to the LA, then the best overall reagent will be the one with the best sensitivity to the most important need for the laboratory (usually heparin monitoring). Therefore, a reagent should be chosen based on the primary monitoring requirements of the aPTT assay, and greater than 90% of the patients with the LA will be detected. PMID- 1497466 TI - Fine-needle aspiration cytology of the adrenal gland. Fifty biopsies in 48 patients. AB - Fine-needle aspiration biopsy of 50 adrenal masses from 48 patients was performed between 1984 and 1991. The series consisted of 28 males and 20 females, with an age range of 12 months to 79 years (mean age, 55 years). Clinical and/or pathologic follow-up was available in 37 patients. Fine-needle aspiration was diagnostic in all 29 malignant cases having follow-up, with no false-positive diagnoses. There were six primary malignancies (three neuroblastomas, two pheochromocytomas, and one adrenal cortical carcinoma) and 23 metastatic lesions. Of these, the lung was the most frequent primary malignancy (60%), followed by melanoma and renal cell carcinoma (8.6% each). The remaining nonmalignant fine needle aspiration diagnoses were adrenal cortical neoplasms (most likely adenoma), adrenal cortical hyperplasia, myelolipoma, benign adrenal tissue, and abscess. Based on clinical follow-up, three other adrenal adenomas were not diagnosed by fine-needle aspiration. Six biopsy specimens (12%) were insufficient for diagnosis. Ancillary studies including electron microscopy and/or immunocytochemistry were performed on 13 malignant aspirates and provided additional confirmation of the cytology diagnosis in 12 cases. This study confirms that fine-needle aspiration is a sensitive and highly specific procedure for the evaluation of primary and metastatic malignancies involving the adrenal gland. The technique is less useful in the workup of benign processes but, in some instances, can provide specific diagnostic information. PMID- 1497467 TI - Rhabdomyosarcoma. A new classification scheme related to prognosis. AB - We classified 159 cases of rhabdomyosarcoma (RMS) according to the conventional scheme adopted by the World Health Organization and a modified conventional scheme established at the National Cancer Institute (NCI), Bethesda, Md. The major modification in the NCI scheme was the inclusion of compact round-cell RMS with scant myogenesis in the group of alveolar RMS despite lack of an alveolar architecture. These tumors were previously considered to be embryonal RMS, but their cytologic features are quite different from those seen in embryonal RMS and are indistinguishable from those encountered in alveolar RMS. These tumors are referred to as "solid alveolar RMS." Survival curves were constructed with the method of Kaplan-Meier and compared with the unstratified and stratified methods of Mantel-Haenszel (with stratification factors being stage, site, and age) and with the Cox regression analysis. Both histologic schemes showed a statistically significant prognostic value in unstratified analyses, but the NCI scheme demonstrated prognostic value even in stratified analyses and in the Cox regression analysis in our series of cases. The data indicate that the NCI scheme can serve as a highly predictive, independent prognostic factor in RMS and that the alveolar category should be expanded to include the solid round-cell RMS, even in the absence of a classic alveolar architecture. PMID- 1497468 TI - Lack of prognostic value of histopathologic parameters in Hodgkin's disease, nodular sclerosis type. A study of 123 patients with limited stage disease who had undergone laparotomy and were treated with radiation therapy. AB - The value of histopathologic parameters in predicting the long-term overall survival probabilities was studied in a series of 123 patients with pathologic stage IA, IB, IIA, IIB, or IIIA Hodgkin's disease, nodular sclerosis type who were treated with curative radiation therapy. The parameters that were studied included the relative proportion of atypical vs reactive cells, amount of eosinophils, presence of necrosis, degree of mitotic activity, intensity of different types of mesenchymal reactions, classification in three subtypes (ie, lymphocyte predominance, mixed cellularity, and lymphocyte depletion) or in two grades (ie, grades 1 and 2), and identification of the syncytial variant. For each parameter, the association with clinical risk factors was also analyzed. The results of this study show that there are no pathologic features that carry a significant predictive value of the overall survival. PMID- 1497469 TI - Abdominal visceral peliosis associated with bacillary angiomatosis. Ultrastructural evidence of endothelial destruction by bacilli. AB - Peliosis involving solid internal organs is a rare entity, and it has been reported in association with chronic debilitating diseases. Bacillary angiomatosis (BA), on the other hand, is a recently identified lesion found virtually only in individuals infected by the human immunodeficiency virus. We describe herein two cases of visceral BA and peliosis in human immunodeficiency virus-infected patients. Based on light and electron microscopic findings, we conclude that (1) BA bacilli present in the hepatic sinusoidal endothelial cells, in a suitable host milieu, may be the causative agents of peliosis hepatis; (2) BA bacilli can be found both intracellularly and extracellularly; and (3) peliosis is also identified in association with BA in abdominal lymph nodes. PMID- 1497470 TI - Angiokeratoma of the clitoris. AB - A 25-year-old woman, multigravida, presented with a dark ulcerated tumor of the clitoris. Histologic examination demonstrated an angiokeratoma, a benign telangiectatic vascular tumor. To our knowledge, this is the first report of angiokeratoma of the clitoris and only the fifth describing vascular tumor of this organ. The clinical differential diagnosis of angiokeratoma and of clitoral tumors includes malignant neoplasms such as melanoma. Biopsy with histologic examination is, therefore, recommended to ensure appropriate treatment of these unusual tumors. PMID- 1497471 TI - Pol Andre Bouin, MD (1870-1962). Bouin's fixative and other contributions to medicine. AB - Pol Andre Bouin was a distinguished French scientist who gained international reputation at the turn of the century for his work in histology and reproductive endocrinology. His name has been retained eponymously in the fixative he described in 1897, today known as "Bouin's fixative." The fixative that bears his name is only one of many contributions he made to academic medicine. PMID- 1497472 TI - Robert Jesse Stoller 1924-1991. PMID- 1497473 TI - Sexual behavior patterns of customers of male street prostitutes. AB - Information about male customers of male prostitutes, including sociodemographic and life-style characteristics, sexual and drug use behaviors, and knowledge about HIV infection were collected from a convenience sample of 211 male street prostitutes and a convenience sample of 15 male customers as part of a feasibility study. Data from these two groups indicate that despite knowledge of HIV infection and its transmission, customers engage in high-risk sexual and drug use behaviors with prostitutes. Because there is a high HIV infection rate within the male prostitute sample (175/1000) and because these customers for the most part describe themselves as bisexual or heterosexual, it is likely that male customers of male prostitutes serve as a vector of transmission of HIV infection to their other partners including the heterosexual population. PMID- 1497474 TI - Divorce and sex. AB - Studies on the sex lives of the divorced are relatively few and somewhat dated. Although they give a rather optimistic view of the subject, this research is flawed by high respondent refusal rates and poor representativeness of samples. Further, a major gap in this literature is that the possible predictors of sexual activity of the divorced remain largely unexplored. The present study, using national data on 340 divorced people, indicates a much lower level of sexual activity than found in past research. Regression analyses find that both number of partners and sex frequency are related to religiosity, education, and political liberality. Future research can explore the impact of low sexual activity among the divorced on indicators of emotional well-being. PMID- 1497475 TI - The relationship of sexual daydreaming to sexual activity, sexual drive, and sexual attitudes for women across the life-span. AB - The association among sexual daydreaming and sexual attitudes and activity was examined in a cross-sectional life-span sample of women (N = 117, 26 to 78 years). Sexual daydreaming was measured using the Imaginal Processes Inventory (IPI) while sexual history measures of sexual activity, sexual drive, and sexual attitudes were derived from a comprehensive personal interview. A factor analysis and varimax rotation of the sexual history variables, age, and the Sexual Daydream Scale of the IPI revealed three primary factors representing dimensions of sexual activity and drive, attitudes toward sexual activity, and sexual satisfaction. Age was associated with less sexual daydreaming, less sexual drive, less sexual activity, and more negative sexual attitudes. Sexual daydreaming varied directly with sexual drive and sexual activity and with a positive sexual attitude. PMID- 1497476 TI - Vibrotactile stimulation enhances sexual response in sexually functional men: a study using concomitant measures of erection. AB - The role of vibrotactile stimulation on the penis in producing erection was investigated in 34 sexually functional men. Subjects were presented with three stimulus segments: erotic video (VID); vibrotactile stimulation (VT) applied to the underside of the penis; and combined vibrotactile and erotic video stimulation (VID+VT). Maximum erectile response was recorded to each stimulus using both an erectiometer and a Barlow strain gauge. Self-reported sexual arousal and affective response to each stimulus segment were also obtained. Results indicated significant variation in erectile response and self-reported arousal over the stimulus segments. Erectile response was lowest to VT alone and highest to VID+VT for both erectile measures, although the pattern of change across stimuli was different for each measure. Self-reported sexual arousal was consistent with erectile measures, but the difference between VID and VID+VT was not statistically significant. VT stimulation alone was perceived as somewhat unpleasant; both VID and VID+VT were perceived as more pleasant than VT, but VID and VID+VT did not differ significantly from each other. This study demonstrates that, while not perceived as more pleasurable or arousing, VT stimulation on the penis combined with erotic video stimulation augments erectile response in functional men in a controlled laboratory situation. The possible use of this methodology for the improved study of men with sexual dysfunctions is discussed. PMID- 1497477 TI - Buspirone hydrochloride in the treatment of an atypical paraphilia. AB - A case report involving buspirone hydrochloride in the successful treatment of a patient with an atypical paraphilia and transvestic fetishism is presented. Treatment outcome was assessed by the patient's self-report as well as by retrospective examination of detailed notes about paraphilia fantasies which unknown to the therapists, had been kept by the patient. Preliminary evidence indicates that buspirone appears to effectively treat some paraphilias. PMID- 1497478 TI - Effects of cigarette smoke on the antibody responses to thymic independent antigens from different lymphoid tissues of mice. AB - The influence of cigarette smoke on the humoral immune response of mice was investigated in lymphocytes derived from the spleen, bone marrow (BM) and mesenteric lymph nodes (MLN). Mice of the DBA/2J or C57BL/6 strain were exposed to cigarette smoke of a standard research cigarette, 2R1, twice a day, ten puffs each in morning and afternoon for 20, 40 or 60 weeks. At the end of the smoking period, animals were immunized intraperitoneally with the thymic independent antigens polyvinyl pyrrolidone (PVP) or trinitrophenyl (TNP)-Ficoll. The antibody responses were analyzed using sheep red blood cells coated with PVP or TNP, in a plaque forming cell (PFC) assay. The results indicate a statistically significant inhibition of the antibody response induced by PVP but not by TNP-Ficoll in splenic B cells of smoke exposed mice compared to sham controls. When tested in other lymphoid organs, there was higher anti-TNP PFC response from the BM and MLN cells of smoke exposed animals compared to sham controls. PMID- 1497479 TI - Oral and dermal application of 2,4-dichlorophenoxyacetic acid sodium and dimethylamine salts to male rats: investigations on absorption and excretion as well as induction of hepatic mixed-function oxidase activities. AB - Absorption and urinary excretion of 2,4-dichlorophenoxyacetic acid sodium (sodium 2,4-D) and 2,4-dichlorophenoxyacetic acid dimethylammonium (2,4-DMA) salts were examined after single oral and mid-dorsal skin applications of the herbicides to male rats. Doses of 2.6 mg 2,4-D/kg body wt (sodium 2,4-D) and 1.9 mg 2,4-D/kg body wt (2,4-DMA) were applied. Quantitatively, with both salts, most of the orally administered herbicide (over 90%) was excreted in urine within 28 h. However, 2,4-D urinary peak concentrations were measured 4.5 and 20.5 h after dosing with 2,4-DMA and sodium 2,4-D, respectively. Additionally, the volume of urine in the oral study was significantly increased with both salts when compared with the controls or the dermal exposure. After topical application, 2,4-D absorption was much lower than in the oral study. Urinary excretion only reached about 10 and 15% of the applied dose for sodium 2,4-D and 2,4-DMA, respectively, by 5 days post-treatment. Further, we found some elevations in hepatic cytochrome P-450 activities. Ethylmorphine N-demethylase was only slightly induced by the herbicides while ethoxyresorufin O-deethylase activity was increased nearly 2 fold by sodium 2,4-D. PMID- 1497480 TI - Inhibition of ferrochelatase and accumulation of porphyrins in mouse hepatocyte cultures exposed to porphyrinogenic chemicals. AB - The ability of 3,5-diethoxycarbonyl-1,4-dihydrocollidine (DDC), 3,5 diethoxycarbonyl-4-ethyl-1,4-dihydro-2,6-dimethylpyridine (EDDC) and griseofulvin to induce porphyria in primary cultures of mouse hepatocytes has been examined. Exposure of cultured mouse hepatocytes to DDC, EDDC or griseofulvin resulted in a marked inhibition of ferrochelatase which was sustained over the 4-day exposure period. Maximal concentrations of DDC (25 microM), EDDC (25 microM) and griseofulvin (25 microM) resulted in 14-fold, 30-fold and 9-fold increases, respectively, in total porphyrin in the culture medium. Analysis of the porphyrins accumulating indicated a predominance of protoporphyrin with all three xenobiotics. Addition of 5-aminolaevulinic acid (ALA) to mouse hepatocyte cultures (10-1000 microM) resulted in much larger increases (up to 164-fold) in porphyrin accumulation in the medium and the porphyrin accumulating was predominantly uroporphyrin. These studies have demonstrated that primary cultures of mouse hepatocytes provide a valid mechanism-based in vitro model of the hepatic porphyrias produced by the dihydropyridines and griseofulvin in mice. PMID- 1497481 TI - Studies on the hepatotoxicity induced by bis (tributyltin) oxide. AB - The toxic effects of bis (tributyltin) oxide (TBTO) on the rat liver were studied with an electron microscope and the accumulation sites of tin were determined with an X-ray microanalyzer. The activities of serum enzymes and the concentration of serum bilirubin were also analyzed. Male Wistar rats received an intramuscular injection of 0.5 ml/kg of TBTO. Marked swelling of the mitochondria appeared in the hepatocytes 4 h after injection of TBTO. Cytoplasmic vacuoles, which contained degenerated mitochondria, gradually increased in number in these hepatocytes. This in turn may have caused a decrease in the volume of hepatic cell cords and an enlargement of sinusoids in the entire hepatic lobule. However, fine structures of intrahepatic bile ducts were not altered. By X-ray microanalysis, tin peaks were preferentially obtained from swollen mitochondria of the hepatocytes. By polarographic analysis of the respiratory responses of mitochondria, it was demonstrated that rates of state 4 respiration and respiratory control ratio were significantly disturbed in TBTO-treated rats in comparison with those of controls. The activities of AST (aspartate aminotransferase) and ALT (alanine aminotransferase) were significantly increased after TBTO treatment, but those of ALP (alkaline phosphatase), LAP (leucine aminopeptidase) and total bilirubin were not changed. These results indicated that parenterally administered TBTO accumulated in the liver cell mitochondria and disturbed oxidative phosphorylation. Mitochondrial dysfunction might induce severe damage of the hepatocytes. Four days after injection of TBTO, hepatic structures and chemical indices were almost restored by the regeneration of hepatocytes. PMID- 1497482 TI - Developmental toxicity evaluation of gallium nitrate in mice. AB - Gallium nitrate, a drug with antitumor activity, is presently undergoing clinical trials as a chemotherapeutic agent for the treatment of certain malignancies. Since there are very limited published animal toxicity data available, this study was conducted to investigate the potential adverse developmental effects of this drug. Pregnant Swiss mice were administered intraperitoneally gallium nitrate at 12.5, 25, 50, and 100 mg/kg/day on days 6, 8, 10, 12, and 14 of gestation. Monitors for maternal toxicity were body weight, food consumption and clinical signs. At sacrifice (day 18) maternal weight, liver and kidney weights, and gravid uterine weights were measured. Gestational parameters monitored were numbers of total implants, resorptions, postimplantation losses, and dead fetuses. Live fetuses were sexed, weighted, and examined for external, internal and skeletal malformations and variations. Maternal toxicity was noted in all the gallium nitrate-treated groups. Embryo/fetal toxicity was evidenced by a decrease in the number of viable implants, a reduction in fetal weight, and an increase in the number of skeletal variations (12.5, 25, 50 and 100 mg/kg). No significant increase in the incidence of malformations was observed at 12.5, 25, or 50 mg/kg. The no-observable-adverse-effect level (NOAEL) for both maternal and developmental toxicity of gallium nitrate was less than 12.5 mg/kg. PMID- 1497483 TI - Teratogenicity of arotinoids (retinoids) in the rat whole embryo culture. AB - Structural modifications of the arotinoid molecule RO 13-7410 led to a difference in the teratogenic potencies of more than five orders of magnitude in mice in vivo and in micromass cultures of rat embryonic limb bud cells (Kistler et al. 1990). Five of these retinoids were selected and tested in rat whole embryo culture to determine the suitability of this in vitro test system for the identification of potentially non-teratogenic derivatives among this class of chemicals. The highest concentrations of the compounds with no effects (NOAEL) on general conceptus growth, on differentiation and on the frequency of dysmorphogenic embryos in vitro were compared with the lowest effective teratogenic doses in vivo (LOAEL) or with the concentrations leading to 50% inhibition of limb bud cell differentiation (IC50) in vitro. NOAEL's for the parameters of conceptus development ranged from 10(-5) micrograms/ml (0.03 nM) to 10 micrograms/ml (28.7 microM) for the compounds tested. These correlated very well with LOAEL and IC50 (R greater than 0.95). The types of dysmorphogenesis in vitro were those typical for retinoids, and for the most part resembled the malformations found in vivo. We conclude that the whole embryo culture system is a useful tool for the preliminary testing of retinoids. PMID- 1497484 TI - Effects of megadoses of pyridoxine on spermatogenesis and male reproductive organs in rats. AB - Although it has been indicated that many neurotoxicants also cause reproductive toxicity, the reproductive toxicity of megadoses of pyridoxine, which is a neurotoxicant, has not been studied. In this paper, we studied the effects of megadoses of pyridoxine on male reproductive organs. Pyridoxine hydrochloride, 125 mg/kg, 250 mg/kg, 500 mg/kg or 1000 mg/kg, daily, was intraperitoneally injected into Wistar male rats 5 days a week for 2 or 6 weeks, and its effects on the male reproductive organs were investigated. After 2 weeks of administration, absolute weights of the testis in the 500 and 1000 mg/kg epididymis in all the exposed groups and prostate gland in the 1000 mg/kg group decreased, and mature spermatid counts in the testis decreased in the 1000 mg/kg group. After 6 weeks administration, the absolute and relative weights of the testis, epididymis, prostate gland and seminal vesicle decreased in the 500 mg/kg and 1000 mg/kg groups, and mature spermatid counts in the testis and sperm counts in the epididymis decreased in these groups. Among the marker enzymes of the testicular cells, LDH-X activity decreased, and beta-glucuronidase activity, cytochrome P 450 content and cytochrome b5 content increased in the 1000 mg/kg group. Plasma testosterone concentration did not significantly alter in all the exposed groups. From these results, it was concluded that megadoses of pyridoxine affected the spermatogenesis and decreased reproductive organ weights in the rat. PMID- 1497485 TI - Mechanism of soman-induced contractions in canine tracheal smooth muscle. AB - The actions of the irreversible organophosphorus cholinesterase (ChE) inhibitor soman were investigated on canine tracheal smooth muscle in vitro. Concentrations of soman greater than or equal to 1 nM increased the amplitude and decay of contractions elicited by electric field stimulation. The effect on decay showed a marked dependence on stimulation frequency, undergoing a 2.4-fold increase between 3 and 60 Hz. Soman also potentiated tensions due to bath applied acetylcholine (ACh). Little or no potentiation was observed for contractions elicited by carbamylcholine, an agonist that is not hydrolyzed by ChE. Concentration of soman greater than or equal to 3 nM led to the appearance of sustained contractures. These contractures developed with a delayed onset and were well correlated with ChE activity. Alkylation of muscarinic receptors by propylbenzilylcholine mustard antagonized the actions of soman on both spontaneous and electrically-evoked muscle contractions. The results are consistent with a mechanism in which the toxic actions of soman are mediated by accumulation of neurally-released ACh secondary to inhibition of ChE activity. An important factor in this accumulation is suggested to be the buffering effect of the muscarinic receptors on the efflux of ACh from the neuroeffector junction. PMID- 1497486 TI - Interaction of obidoxime with sarin in aqueous solution. AB - The interaction of obidoxime (Toxogonin) with sarin was shown by different analytical methods. The UV spectrum of obidoxime at pH 7.4 yields two absorption maxima, lambda 1 = 284 nm and lambda 2 = 353 nm. The peak at lambda 2 = 353 nm is representative for the amount of zwitter-ionic obidoxime, i.e. the active form of obidoxime. By addition of sarin, lambda 1 shifts immediately to 278 nm and the intensity at lambda 2 decreases, thus indicating an interaction. TLC and 31P-NMR evidence shows that both mono-phosphonylated and diphosphonylated obidoximes are present. Decomposition of phosphonylated obidoxime in MOPS (3-[N-morpholino] propanesulfonic acid) buffered D2O at pH 7.4 occurs with t1/2 = 13.3 min at 24 degrees C. Decomposition of di-phosphonylated obidoxime is faster. It is suggested that decomposition of di-phosphonylated obidoxime occurs through the mono-phosphonylated form. Formation and decomposition of mono- and di phosphonylated obidoxime is pH dependent. We conclude that obidoxime exerts a detoxifying effect by capturing free sarin molecules and thus increasing its polarity. Thereby the transition of sarin through the blood-brain barrier is restricted and its renal elimination facilitated. PMID- 1497487 TI - Efficacy of HLo-7 and pyrimidoxime as antidotes of nerve agent poisoning in mice. AB - The toxicity and efficacy of two oximes, HLo-7 and pyrimidoxime, were evaluated in mice and compared to those obtained with HI-6. HLo-7 and pyrimidoxime produced 24 h LD50 values of 356 and 291 mg/kg (i.p.), respectively. In combination with atropine (17.4 mg/kg, i.p.), HLo-7 was a very efficient therapy against poisoning by 3 x LD50 dose of soman, sarin and GF and 2 x LD50 dose of tabun with ED50 values of 12.4, 0.31, 0.32 and 25.2 mg/kg, respectively. In contrast, pyrimidoxime was a relatively poor therapy which resulted in ED50 values of greater than 150, 5.88, 100 and 71 mg/kg against poisoning by soman, sarin, GF and tabun, respectively. HLo-7 produced significant (p less than 0.05) reactivation of phosphorylated acetylcholinesterase, in vivo, resulting in 47, 38, 27 and 10% reactivation of sarin, GF, soman and tabun inhibited mouse diaphragm acetylcholinesterase, respectively. HLo-7 also antagonized sarin induced hypothermia in mice suggesting that it reactivated central acetylcholinesterase. The potential of HLo-7 as a replacement oxime for the treatment of nerve agent poisoning is discussed. PMID- 1497488 TI - Assessment of biological activities of mixtures of polychlorinated dibenzo-p dioxins (PCDDs) and their constituents in human HepG2 cells. AB - Dose-response curves of the induction of P4501A1-dependent 7-ethoxyresorufin O deethylase (EROD) were analyzed in human hepatoma HepG2 cells treated with defined mixtures of polychlorinated dibenzo-p-dioxins (PCDDs) and their 2,3,7,8 substituted constituents, similar to previous studies with rat hepatocytes and H4IIE cells (Schrenk et al. 1991). PCDDs appear to act less potent in human HepG2 cells in comparison with rat cells. For example, EC50 values of 2,3,7,8-Cl4DD were 8-fold and 19-fold higher than in rat H4IIE cells and hepatocytes, respectively. EC50 values of PCDDs were compared with that of 2,3,7,8-Cl4DD and expressed as 2,3,7,8-Cl4DD equivalents (TEs). Although the rank order of PCDD potencies was similar, TEs for some PCDDs (1,2,3,7,8-Cl5DD; TE = 0.75 and 1,2,3,7,8-Cl6DD; TE = 0.61) were found to be higher than in the rat system. In contrast to rat cells no significant induction of EROD could be detected with Cl8DD in HepG2 cells up to its limit of solubility. Experimentally determined TEs of PCDD mixtures containing 49 constituents were found to be largely due to additive effects of their 2,3,7,8-substituted constituents. PMID- 1497489 TI - Cytotoxicity of mebendazole against established cell lines from the human, rat, and mouse liver. AB - The direct cytotoxicity of mebendazole (MBZ) was investigated by using cell lines derived from human, mouse and rat liver. It was demonstrated that Chang liver cells (derived from human liver) were more sensitive to the cytotoxic effects of MBZ than the other two cell lines. Longer incubation of the cells with MBZ resulted in stronger toxicity, and the cytotoxicity was dependent on the MBZ concentration above a certain threshold value (0.25-0.50 mg/l in a 42-h culture). Inhibition of the proliferation of Chang liver cells by MBZ was detected at a concentration of 0.008 mg/l, a lower concentration than that having a cytotoxic effect. The other two cell lines were less sensitive to the inhibitory effect of MBZ. Proliferation of human mononuclear cells following stimulation by phytohemagglutinin (PHA) was inhibited by MBZ, and this inhibition was more extensive than that of cells stimulated with whole formalin-treated Pseudomonas aeruginosa. It is suggested that dividing cells may be more sensitive to MBZ cytotoxicity. This anti-proliferative effect may be related to its clinically known side effects, such as hepatotoxicity and bone marrow suppression. PMID- 1497490 TI - Hematological toxicity of tetrachloroethylene in mice. AB - Female C57/BL/6 x DBA/2 hybrid mice were exposed to two concentrations (270 and 135 ppm) of tetrachloroethylene (PER) in inhalation chambers for 6 h/day, 5 days per week, up to 11.5 weeks (270 ppm) and 7.5 weeks (135 ppm), respectively, followed by a 3-week exposure-free period. In the peripheral blood a reduction of lymphocytes/monocytes and of neutrophils was observed with an almost complete regeneration in the exposure-free period. A reticulocytosis during and also after the exposure indicated a compensatory reaction in the erythroid cell system. Bone marrow pluripotent stem cells (CFU-S) were not affected up to 7.5 weeks. Erythroid committed cells (BFU-E and CFU-E) did react, with a reduction of CFU-E numbers at 7.5 and 11.5 weeks. A slight reduction of CFU-C numbers at 7.5 weeks indicated, in accordance with the peripheral blood data, a disturbance of the granulocytic cell series as well. PMID- 1497491 TI - Biologically significant serum vitamin B12 deficiency in multiple sclerosis inadequately documented. PMID- 1497492 TI - The value of brain magnetic resonance imaging in multiple sclerosis. PMID- 1497493 TI - Gadolinium-pentetic acid magnetic resonance imaging in patients with relapsing remitting multiple sclerosis. AB - Ten patients with relapsing-remitting multiple sclerosis have been studied by serial gadolinium-pentetic acid magnetic resonance imaging (MRI) every 14 days for 3 months. At the end of the follow-up, seven relapses occurred in six patients; no therapy was administered during the study. Ninety-three enhancing lesions were collected in eight patients. With regard to the duration of the enhancement, 32 lesions were detected in only one MRI scan and 32 were found in more MRI scans (most of the lesions occurring in two serial examinations). Four old lesions increased their size with delayed enhancement. Correlation was found between the relapses and the gadolinium-pentetic acid-enhancing areas only for one brain-stem and two cervical spinal cord lesions. Gadolinium-pentetic acid MRI provides useful information about activity of the disease that cannot be obtained clinically even if the dynamic of the lesions may be undervalued in old plaques. PMID- 1497494 TI - Effect of age on autonomic and cardiac responses in a rat stroke model. AB - The cardiovascular system and its responses change with increasing age. This has seldom been considered in experimental models of stroke, although most strokes occur in the elderly. We studied 57 male Wistar rats in three age groups: 47 to 70 days old (juvenile), 110 to 152 days old (young adult), and 186 to 245 days old (mature adult), each group being subdivided into experimental and sham operation groups. All rats underwent occlusion or sham occlusion of the left middle cerebral artery and monitoring of the mean arterial blood pressure, heart rate, sympathetic nerve activity, plasma catecholamine levels, and electrocardiogram. Eight of the 12 rats in the oldest group died within 6 hours of the middle cerebral artery occlusion; of these, the youngest was 186 days old. The mature adult rats that died before completion of the experiment showed the highest level of sympathetic nerve activity and the only significant increase in the QT interval of the electrocardiogram. Following middle cerebral artery occlusion, sympathetic nerve activity increased in the young adult rats but most strikingly in the mature adult rats that died before the end of the 6-hour experiments. Plasma norepinephrine levels were significantly elevated at 4 and 6 hours after middle cerebral artery occlusion in the oldest group and only at 6 hours in the juvenile rats. The results of this study are consistent with impaired sympathetic and cardiovascular regulation in the mature adult rat. High sympathetic activity may represent one mechanism leading to fatal cardiac arrhythmias. Age-related impairment of sympathetic regulation may contribute to the higher mortality seen among elderly patients with stroke. PMID- 1497495 TI - Asymmetry of sympathetic consequences of experimental stroke. AB - Asymmetries of sympathetic regulation at the level of the inferior cervical ganglia have long been recognized. Lateralization of autonomic representation may also occur in the brain, since inactivation of the left and right hemispheres by intracarotid amobarbital produces an increase and decrease in heart rate, respectively. However, this conclusion has remained tentative, since the differential effect of lateralized brain lesions on sympathetic activity has not been studied systematically. Forty-eight urethan-anesthetized Wistar rats were divided into three groups: a group given left middle cerebral artery occlusion, and a group given sham operation. Heart rate, mean arterial blood pressure, renal sympathetic nerve discharge, and electrocardiogram were monitored throughout the 4-hour experiments. Plasma epinephrine and norepinephrine levels were measured at baseline and 1 and 4 hours after occlusion or sham occlusion. The mean arterial pressure decreased in the group given sham operation and to lesser extent in the group given left middle cerebral artery occlusion. By contrast, mean arterial pressure did not fall in the group given right middle cerebral artery occlusion and at 4 hours was significantly higher than control values in the sham-occluded rats. Renal sympathetic nerve discharge was decreased in the sham-occluded group, increased significantly from 20 minutes to 2 hours in the group given left middle cerebral artery occlusion, and increased from about 20 minutes to the end of the experiment in the group given right middle cerebral artery occlusion. The plasma norepinephrine level was significantly elevated at 1 hour (93%) and 4 hours (44%) only in the group given right middle cerebral artery occlusion.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1497497 TI - Biological significance of iron-related magnetic resonance imaging changes in the brain. AB - Iron, an essential element for basic cellular metabolism, regularly accumulates in certain brain areas in normal subjects and in patients with certain diseases. Magnetic resonance imaging can depict iron deposition, offering a singular opportunity to correlate the regional iron content with the functional status of the human brain in vivo. We studied the relationship between age and the iron related signal loss on T2-weighted images in basal ganglia, and observed a strongly significant signal decrease in the globus pallidus at the age of brain development (first two decades of life), but we found no such decrease in later years. Moreover, in healthy adults, subject-to-subject variability was relevant in changes due to iron deposition in magnetic resonance imaging. We found increased signal loss to be associated with poor performance on motor and specific cognitive tasks, suggesting that these image changes can provide functional information with respect to the brain in normal subjects. PMID- 1497496 TI - Thalamic stroke. Presentation and prognosis of infarcts and hemorrhages. AB - Thalamic strokes in 62 patients selected from the Stroke Data Bank were studied to determine differences among 18 infarctions (INF), 23 localized hemorrhages (ICH), and 21 hematomas with ventricular extension (IVH). Stupor or coma at onset occurred more frequently in the IVH (62%) than in the INF (6%) or ICH (13%) groups and was reflected in significantly lower median Glasgow Coma Scores in the IVH group (7) than in the INF (15) and ICH (14) groups. Although ocular movements were more frequently abnormal in the IVH group compared with the ICH and INF groups, no significant differences were found in the frequency of motor or sensory deficits. Among the 62 strokes, 32 had restricted lesions of the posterolateral (n = 9), anterior (n = 3), paramedian (n = 7), and dorsal (n = 13) portions of the thalamus. Differences in consciousness and in motor, sensory, and oculomotor deficits were found among the topographic subgroups. Stroke-related deaths occurred in 52% of IVH cases, 13% of ICH cases, and no cases of INF. Median lesion volume as detected with computed tomography was greater in hemorrhages (INF, 2 cm3; ICH, 10 cm3; IVH, 16 cm3), with mortality related to increasing hematoma size. Coma, Glasgow Coma Score lower than 9, weakness score greater than 15 of a possible 30, abnormal ocular movements, and fixed pupils were also associated with stroke-related mortality. We conclude that the initial neurologic syndrome does not discriminate infarcts from intrathalamic hemorrhages. Ventricular extension, however, causes significantly more severe deficits and higher mortality. PMID- 1497498 TI - Increased metallothionein in the liver and kidney of patients with amyotrophic lateral sclerosis. AB - To evaluate the putative role of metals and trace elements in the pathogenesis of classic amyotrophic lateral sclerosis, we studied the metallothionein levels in liver and kidney samples obtained at autopsy from 24 patients with amyotrophic lateral sclerosis and 18 controls. To assay metallothioneins and copper, cadmium, and zinc bound to metallothioneins, we used high-performance liquid chromatography directly coupled to flame atomic absorption spectrometry. Total cadmium, zinc, and copper concentrations were determined separately with the use of graphite furnace atomic absorption spectrometry with Zeeman background correction. The median liver metallothionein level was 60.3 mg/kg (range, 9 to 318 mg/kg) in the patients with amyotrophic lateral sclerosis and 12.6 mg/kg (range, 0 to 104.5 mg/kg) in the controls. In the kidney, median metallothionein levels were 126.9 mg/kg (range, 44 to 387 mg/kg) in the patients with amyotrophic lateral sclerosis and 64 mg/kg (range, 13.1 to 187 mg/kg) in the controls. Total zinc, cadmium, and copper concentrations, as measured by atomic absorption spectrometry, were not significantly different in patients vs controls. Our finding of elevated metallothionein levels in organs from patients with amyotrophic lateral sclerosis may indicate an increased exposure to metals. PMID- 1497501 TI - Peripheral mechanical loading and the mechanism of the tremor of chronic alcoholism. AB - The tremor of chronic alcoholism, although clinically similar to essential tremor, has been considered a distinct syndrome. Its underlying mechanism was analyzed in five patients (none in the acute stages of alcohol withdrawal) hospitalized in an alcohol detoxification program. All five patients performed tracking tasks in which they pursued a linearly moving "target" light with a response light that they controlled by flexion-extension activity of the wrist. Stationary and dynamic targets were used with both isometric and unconstrained wrist mechanical interfaces. Frequency, torque, and displacement tremor characteristics were examined under varying inertial loading or isometric voluntary torque conditions. Two simultaneous tremor components were present in all patients: a prominent 4- to 7-Hz low-frequency peak and a smaller-amplitude 9.4- to 9.6-Hz high-frequency peak. As the inertia of the hand was augmented during unconstrained tasks, the low-frequency peak decreased, while the high frequency peak was unaffected. As required voluntary effort was increased during isometric testing, the amplitude of the low-frequency peak increased. These findings suggest that the low-frequency peak represents the significant pathologic component of the tremor of chronic alcoholism and that it has a biomechanical reflex mechanism similar to that of the lower-amplitude normal physiologic tremor. PMID- 1497499 TI - Local cerebral blood flow and its response to intravenous levodopa in progressive supranuclear palsy. Comparison with Parkinson's disease. AB - The local cerebral blood flow (LCBF) at steady state and after the intravenous administration of levodopa (1 mg/kg) was measured by the xenon-enhanced computed tomographic method in six patients with progressive supranuclear palsy (PSP) and in nine patients with idiopathic Parkinson's disease. The baseline LCBF values in most brain regions in patients with PSP were lower than those in patients with Parkinson's disease, and hyperfrontality of the LCBF was lost. In patients with Parkinson's disease, the injection of levodopa markedly increased LCBF, especially in the striatum, thalamus, and internal capsule (approximately 40%). In patients with PSP, however, levodopa did not increase the LCBF in all brain regions examined. The LCBF increases after the administration of levodopa in patients with Parkinson's disease may be secondary to metabolic activation of the dopaminergic system. The different LCBF responses to levodopa between patients with PSP and those with Parkinson's disease may reflect differences in pathologic features, such as in the degree of preservation of nigrostriatal dopaminergic neurons and the distribution and density of dopamine receptors, and are also related to the clinical effectiveness of levodopa therapy. PMID- 1497500 TI - Cerebral brain metabolism in adult dyslexic subjects assessed with positron emission tomography during performance of an auditory task. AB - Ten dyslexic adults (aged 33.5 +/- 7.3 years, nine men, one woman) and 10 age-, sex- and handedness-matched control subjects (aged 33.6 +/- 5.8 years) performed an auditory syllable discrimination task during 18-fluoro-2-deoxyglucose uptake, and then underwent positron emission tomographic scans. A second normal control group performed an analogous visual discrimination task. Dyslexic subjects experienced greater difficulty and made significantly more errors in performing the auditory task. There were no differences in brain metabolic rates in lateral cortical areas (frontal, parietal, temporal, and occipital lobes). A significant difference emerged in the medial temporal lobe, with dyslexic subjects having significantly higher absolute and relative brain metabolism along an anterior posterior gradient than normal adults. These data support the hypothesis of altered cerebral processing of auditory stimuli in patients with dyslexia. PMID- 1497502 TI - Spinal epidural abscess. Early detection with gadolinium magnetic resonance imaging. AB - To emphasize the importance of timely diagnosis of spinal epidural abscess, thirteen patients admitted to a single general hospital are presented. In 10 patients, diagnosis was not appreciated at the time of presentation. After treatment, four remained paraparetic and three died. Nine patients had predisposing factors, including seven with infections at sites other than the spinal canal. Staphylococcus aureus was the predominant organism. Outcome was equally devastating for the seven patients with acute and the six patients with chronic infections. Gadolinium-enhanced magnetic resonance imaging was the most useful diagnostic test, and we recommend that it be performed promptly in any patient with clinical features suggesting spinal epidural abscess since early surgical drainage and appropriate antibiotics may yield a favorable outcome. PMID- 1497503 TI - Further observations on the pathology of subcortical lesions identified on magnetic resonance imaging. AB - We performed postmortem magnetic resonance imaging and pathologic examinations on the brains of seven consecutive patients older than 50 years of age who died of non-neurologic causes. Multiple hyperintense subcortical lesions were identified in each patient, and a total of 29 lesions were examined histologically (eight rims, six caps, six punctate lesions, and nine patches). Rims were characterized by subependymal gliosis and loss of the ependymal lining; caps were associated with myelin pallor, gliosis, and arteriosclerosis; punctate lesions were characterized by dilated perivascular spaces and perivascular gliosis; and patches were associated with myelin pallor and dilated perivascular spaces. The pattern of myelin pallor defined the size and shape of caps and patches. Arteriosclerosis was identified in six of six caps, three of six punctate lesions, and in three of nine patches. These data indicate that (1) each type of hyperintense subcortical lesion has a distinct pathologic correlate; (2) arteriosclerosis is not invariably associated with all types of hyperintense subcortical lesions on magnetic resonance imaging; and (3) myelin pallor appears to contribute to the magnetic resonance imaging signal at 1.5 tesla. PMID- 1497504 TI - Meningiomas are not significantly associated with breast cancer. AB - We studied 283 meningiomas seen at the University of Kansas, Kansas City, from 1948 through 1984, identifying all additional nonmeningeal malignancies and primary brain tumors in these patients and calculating the expected number of additional tumors by the use of a person-year method from age and sex-matched cancer incidence data. We determined expected numbers of total neoplasms in our meningioma population as well as the expected numbers in each major organ system for the sexes independently and together. We then calculated standard morbidity ratios and 95% confidence intervals for each tumor type. The number of breast cancers did not reach statistical significance. We found a significantly increased number of second primary brain tumors in women (standard morbidity ratio, 8.0; 95% confidence interval, 2.2 to 20.4) and an increased number of thyroid cancers in both sexes (standard morbidity ratio, 7.5; 95% confidence interval, 1.5 to 21.9). PMID- 1497505 TI - Developmental consequences of childhood frontal lobe damage. AB - A 33-year-old woman underwent neurologic and neuropsychological studies 26 years after she sustained damage to the frontal lobe. The findings of the neurologic examination were normal, and magnetic resonance imaging revealed a lesion in left prefrontal cortex and deep white matter. Cerebral blood flow studies showed an abnormal pattern in both left and right frontal regions. The patient exhibited striking neuropsychological defects in higher cognition, most notably in self regulation of emotion and affect and in social behavior. Analysis of her behavioral development failed to yield a pattern of abrupt onset of defect immediately after the lesion occurred. On the contrary, there was a delayed onset of defects, followed by a period of seeming progression, and finally an arrest of development in adolescence. We suggest that this peculiar pattern is the natural consequence of the varied changes that occurred in brain development and social cognition during the patient's formative years. While certain long-term neuropsychological deficits in our case are similar to those following frontal damage in adults, the delayed onset and progression of deficits are different. PMID- 1497506 TI - Asymmetric cortical degeneration syndromes. A proposed clinical classification. AB - Twenty-six patients presented with slowly progressive focal neurologic symptoms that conformed clinically to one of three categories: asphasia, perceptuomotor dysfunction, or neuropsychiatric dysfunction. Of 12 patients with progressive aphasia, seven were dysfluent and five were fluent. Nine patients had progressive perceptuomotor impairment due to bilateral parietal lobe atrophy, which also included frontal lobe signs in seven patients and occipital lobe signs in three patients. The right hemisphere was more severely involved in five patients and the left hemisphere in four. Five patients had a progressive neuropsychiatric syndrome, and there was also generalized spasticity in three patients due to frontal lobe atrophy. The clinically suspected anatomic localization of cortical atrophy or hypoperfusion in all three categories was confirmed with neuroimaging techniques. A brain biopsy specimen from one patient showed mild, nonspecific degenerative changes. A clinical classification scheme incorporating our observations as well as the observations of others is presented to aid in the recognition of these syndromes. PMID- 1497507 TI - Visual function after photorefractive keratectomy. PMID- 1497508 TI - Larger optic nerve heads have more nerve fibers in normal monkey eyes. PMID- 1497509 TI - High-performance ophthalmology. PMID- 1497510 TI - Bleb leak with hypotony after laser suture lysis and trabeculectomy with mitomycin C. PMID- 1497511 TI - Hypotony maculopathy following trabeculectomy with mitomycin C. PMID- 1497512 TI - Corneal-graft dehiscence secondary to suction-cup device use for contact lens removal. PMID- 1497513 TI - Combined rhegmatogenous-traction retinal detachment following successful treatment of Candida chorioretinitis. PMID- 1497514 TI - Retinopathy due to renovascular hypertension in a patient with non-Hodgkin's lymphoma. PMID- 1497515 TI - Chromosome 14-terminal deletion and cataracts. PMID- 1497516 TI - AMA OKs physician self-referral with stipulations. PMID- 1497517 TI - Who should receive antimetabolites after filtering surgery? PMID- 1497518 TI - A randomized study of trabeculectomy and subconjunctival administration of fluorouracil in primary glaucomas. AB - Forty-one adult patients with primary open angle glaucoma and nine adult patients with chronic angle closure glaucoma underwent trabeculectomy in one eye each. Twenty-one eyes with primary open angle glaucoma and four with chronic angle closure glaucoma were randomly assigned to receive four to six subconjunctival injections of fluorouracil for 10 days after surgery. Twenty-five control eyes did not receive fluorouracil. Intraocular pressure was 20 mm Hg or lower in 24 eyes (96%) in the treatment group after mean follow-up of 17.8 months and in 19 control eyes (76%) after mean follow-up of 17.5 months (P less than .05). Encapsulated bleb developed in three (12%) of the fluorouracil-treated eyes vs two (8%) of the control eyes. A few injections of fluorouracil adequately inhibited scarring. This might be explained by its toxic effect on existing fibroblasts. Overall, trabeculectomy with injection of fluorouracil was found to be efficacious and relatively safe. Further studies regarding late complications are required. PMID- 1497519 TI - Contrast sensitivity and reading through multifocal intraocular lenses. AB - Multifocal intraocular lenses are intended to increase depth of focus for patients with cataracts, but optical considerations predict reduced retinal-image contrast. We evaluated visual performance through multifocal intraocular lenses by measuring contrast sensitivity functions and reading speed for age-matched groups with multifocal and monofocal intraocular lenses and two normal control groups. Contrast sensitivity functions of the patients with multifocal lenses did not differ significantly for optical distances differing by 2.5 diopters, indicating substantial depth of focus. Normal and monofocal contrast sensitivity functions were nearly identical, and both were about a factor of two higher than multifocal contrast sensitivity functions. Patients with multifocal lenses showed deficits in reading speed only for low-contrast text (less than 30%) and small letters (0.2 degree and 1.0 degree). PMID- 1497520 TI - The effect of early cataracts on glare and contrast sensitivity. A pilot study. AB - To establish the effect of cataracts on glare and contrast sensitivity, we graded type and amount of lens opacity in 110 subjects who underwent two glare tests (Brightness Acuity Tester and Berkeley glare test) and two contrast sensitivity tests (a sine-wave test and Pelli-Robson chart). Twenty-seven subjects (25%) had clear lenses (mean visual acuity of 20/20) and 83 subjects (75%) had early lens opacities (mean visual acuity of 20/40) in otherwise normal eyes. Multiple regression techniques were used to control for the effects of age and visual acuity. Glare test scores were significantly lower for nearly all patients with lens opacities than for patients with clear lenses and were the lowest for patients with lenses with posterior subcapsular opacity. Contrast sensitivity scores were lower for all patients with lens opacities than for patients with clear lenses at high frequencies only; all lens opacity groups scores similarly with each other. These results indicate reduced visual function among patients with cataracts whose visual acuity is only minimally impaired. PMID- 1497521 TI - Visual acuity correlates with severity of retinopathy of prematurity in untreated infants weighing 750 g or less at birth. AB - Visual acuity was assessed in 72 patients who weighed 750 g or less at birth, had intact visual pathways as confirmed with computed tomography or magnetic resonance imaging, and had at least one eye evaluated for cicatricial sequelae after active, untreated retinopathy of prematurity without macular detachment (stage 4a or better). Visual acuities were obtained for 137 untreated, sighted eyes. Severity parameters for retinopathy of prematurity (stage of retinopathy of prematurity, refraction [in spherical equivalents], macular ectopia [in disc diameters], and vessel traction [in 30 degrees sectors]) was were significant predictors of visual acuity (P less than .0001) based on results of linear regression and stepwise regression analyses; however, parameters of retinal immaturity (birth weight, gestational age, and zone of retinopathy of prematurity) were not significant predictors of visual acuity. Visual acuity of the study eyes was good (median, 20/30; geometric mean, 20/33.58), with no statistical differences between eyes evaluated on last examination with linear Allen figures and those evaluated with linear Snellen test types. PMID- 1497522 TI - Ocular cosmesis in retinopathy of prematurity. The Cryotherapy for Retinopathy of Prematurity Cooperative Group. AB - We report the externally apparent outcome in the natural history cohort (n = 4099) that was followed up prospectively in the Multicenter Trial of Cryotherapy for Retinopathy of Prematurity. The overall incidence of an adverse cosmetic outcome in the survivors who were examined 12 months post term (n = 2759) was 15.1%. Adverse cosmetic outcomes included strabismus (12.8%), nystagmus (3.3%), total retrolental membrane (1%), epiphora (0.6%), corneal opacity (0.6%), cataract (0.3%), and episcleral hyperemia (0.3%). A comparable subgroup examined 24 months post term showed strabismus (14.4%), nystagmus (2.2%), epiphora (0.5%), corneal opacity (0.7%), cataract (0.5%), episcleral hyperemia (0.5%), lid fissure asymmetry (2.4%), and corneal diameter asymmetry (2.0%). The rate of adverse aesthetic outcome was greatest in eyes that had developed more severe acute retinopathy of prematurity and an unfavorable structural outcome. In patients with bilateral threshold retinopathy of prematurity who underwent no therapeutic ocular procedures, other than randomized assignment to undergo cryotherapy in one eye, more frequent adverse cosmetic outcomes were found in the untreated eyes. PMID- 1497523 TI - Measurement of preretinal oxygen tension in the vitrectomized human eye using fluorine-19 magnetic resonance spectroscopy. AB - We obtained oxygen measurements from a human eye that contained small preretinal droplets of perfluorotributylamine (FTBA) by using fluorine-19 magnetic resonance spectroscopy. These droplets were the remainder of a larger volume of FTBA that was used as an intraoperative retinal tamponade during retinal detachment repair. The spin-lattice relaxation rate ([T1]-1) of the FTBA fluorine nuclide was obtained that could then be related, by direct proportionality, to droplet PO2. With the patient in a supine position, the droplets could be positioned over the macula in the preretinal vitreous space, whereon the FTBA PO2 could be influenced by the preretinal oxygen concentration. Preretinal PO2 values, derived from magnetic resonance spectroscopy, were in the range of 6 to 9 mm Hg, although multiple components were identified that were suggestive of a heterogeneous distribution of PO2 values in the population of droplets. To our knowledge, this investigation is the first to demonstrate the feasibility of this approach to performing long-term, noninvasive preretinal oxygen measurements in the vitrectomized human eye by using small droplets of a liquid perfluorochemical. PMID- 1497524 TI - Combined phacoemulsification, pars plana vitrectomy, and posterior chamber intraocular lens insertion. AB - Eighteen eyes with coexisting cataract and vitreoretinal disease underwent combined phacoemulsification, pars plana vitrectomy, and posterior chamber lens implantation. Preoperative vitreoretinal disease included nonclearing vitreous hemorrhage (eight eyes), vitreous hemorrhage and tractional retinal detachment (three eyes), tractional retinal detachment (one eye), epiretinal membranes (three eyes), peripheral uveitis (two eyes), and a retained intraocular metallic foreign body (one eye). Postoperative visual acuity improved in each case; 14 eyes achieved visual acuity between 20/20 and 20/80 during an average postoperative period of 11 months (range, 3 to 39 months). Perioperative complications included an iatrogenic retinal break (one eye) and pupillary block glaucoma (one eye). Four eyes required YAG laser capsulotomy postoperatively. Phacoemulsification did not interfere with corneal clarity, allowed water-tight wound closure during vitrectomy, and preserved the capsular bag, allowing endocapsular fixation of the posterior chamber lens. Combining phacoemulsification, posterior chamber lens implantation, and pars plana vitrectomy allows rapid visual rehabilitation and functional unaided vision in these eyes. PMID- 1497525 TI - Magnetic resonance imaging. Diverse appearances of uveal malignant melanomas. AB - Fifteen patients with uveal malignant melanomas were studied by magnetic resonance imaging. The magnetic resonance imaging appearances varied from those that have been reported previously to be characteristic of these tumors. In our series, malignant melanomas were of high signal on the T1 sequence and of variable but usually also of high signal on the T2 and Short Tau Inversion Recovery (STIR) sequences, a signal combination rarely described before. We postulate that magnetic resonance imaging appearances may be dependent on variations in histologic factors and on the type and field strength of the scanner used. It is widely believed that the paramagnetic melanin in malignant melanomas gives these tumors characteristic magnetic resonance imaging appearances, but our finding of diverse magnetic resonance imaging appearances for proved malignant melanomas suggests that this may not always be the case. We advise caution in diagnosing malignant melanomas from magnetic resonance imaging appearances alone. PMID- 1497526 TI - Late histopathological findings of neodymium:YAG laser iridotomies in humans. AB - We studied three sector iridectomy specimens from three patients who had undergone neodymium:YAG (Nd:YAG) laser iridotomies 3 to 5 years earlier for treatment of imminent angle closure glaucoma. The specimens were obtained during cataract extraction and were examined by light and transmission electron microscopy. In all iris specimens, the edges of the iridotomy sites consisted of loosely arranged melanocytes, fibrocytes, and vessels. In the iris stroma, there were numerous pigment-laden cells. The iris vessels appeared to be intact; there were no fibrinous aggregates, no inflammatory response or scarring, nor any signs of proliferation of the iris pigment epithelium. Our findings suggest that in humans, iris wound healing after Nd:YAG laser iridotomy occurs without induction of fibrous scars or proliferation of the iris pigment epithelium. This indicates that there is no tendency toward late closure of the iridotomy sites. PMID- 1497528 TI - Corneal endothelial anomalies in the fetal alcohol syndrome. AB - The fetal alcohol syndrome involves various neural crest-derived structures thus causing systemic and ocular malformations. This study investigated anomalies of the corneal endothelium, a neural crest-derived tissue, in eight children affected by fetal alcohol syndrome without known anterior segment anomalies. We performed specular biomicroscopy on the central corneal endothelium. The data were then compared with those from 80 age-matched healthy children, applying the same methods. Significant differences were found between patients with fetal alcohol syndrome and healthy subjects for mean cell density (P = .032), polymegethism (P = .000), and percentage of hexagonal cells (P = .000). We also found a close correlation between endothelial anomalies and auditory dysfunction in the patients with fetal alcohol syndrome. These alterations may be a consequence of alcohol-induced toxic effects on neural crest cells destined to form both the corneal endothelium and the organ of Corti in the same embryogenic period. PMID- 1497527 TI - Effect of continuous circular capsulorhexis and intraocular lens fixation on the blood-aqueous barrier. AB - Permeability across the blood-aqueous barrier to fluorescein was estimated fluorophotometrically in pseudophakic eyes for which a continuous circular capsulorhexis was performed. The permeability index was significantly higher in the in-the-bag fixations than in the out-of-the-bag fixations at 3 and 6 months after surgery, when only bilateral cases were enrolled. Damage to the barrier in eyes with the in-the-bag fixations was attributable to the broad attachment of optics to the anterior capsule, because a positive linear regression was obtained between the permeability index and the doughnut-shaped contact area in eyes with the in-the-bag fixations. The permeability index in eyes with the in-the-bag fixations was as low as that in eyes with the out-of-the-bag fixations when the contact area was small. These results indicate an unfavorable effect of the in the-bag fixation with broad contact of the optics with the anterior capsule and, thus, suggest either an in-the-bag fixation with a large capsulorhexis or an out of-the-bag fixation. PMID- 1497529 TI - National outcomes of cataract extraction. III. Corneal edema and transplant following inpatient surgery. AB - We analyzed the likelihood of rehospitalization for corneal edema or corneal transplantation in all 338,141 Medicare beneficiaries older than 65 years who were admitted to US hospitals for cataract extraction in 1984. The rate of rehospitalization for corneal edema or transplant within 4 years of intracapsular cataract extraction was 1.4%, almost twice the rate associated with extracapsular extraction (0.63%) or phacoemulsification (0.62%; P less than .0001). No significant difference in the rate of corneal transplantation was detected between those undergoing extracapsular cataract extraction and those undergoing phacoemulsification. Among patients who had intracapsular cataract extraction, those who underwent concurrent intraocular lens implantation surgery had a higher rate of rehospitalization for corneal edema or transplantation than those who did not (1.11% vs 0.86%; P = .0003). However, this difference is only manifest starting at about 3 years after surgery. Among patients who underwent extracapsular cataract extraction and phacoemulsification, however, those who underwent intraocular lens implantation during surgery had a lower rate of corneal edema or transplantation than those who did not (0.47% vs 0.74%; P less than .0001). This difference was seen almost immediately after surgery. Cataract surgery accompanied by anterior vitrectomy was associated with a threefold increase in the 4-year rate of corneal edema or transplantation compared with cataract surgery alone (2.42% vs 0.87%; P less than .0001). PMID- 1497530 TI - Correlation of histologic corneal endothelial cell counts with specular microscopic cell density. AB - The central endothelia of 48 eye bank corneas from donors ranging in age from 5 weeks to 88 years were photographed using in vitro specular microscopy. Computer assisted morphometric analysis of the size and shape of endothelial cells was performed, and cell density was calculated. Histologic examination of the corneas after specular microscopy determined endothelial cell counts using x40 objective magnification. The mean endothelial cell counts from five different high-power fields were calculated. Results showed that there is a direct correlation between cell number and specular microscopy cell density (r = .91 and Spearman rank correlation, 0.69; both significant at P less than .01). A nomogram was developed to estimate corneal endothelial cell density from high-power field cell counts of pathologic specimens. PMID- 1497531 TI - Treatment with intravitreal steroid reduces blood-retinal barrier breakdown due to retinal photocoagulation. AB - The effect of corticosteroid treatment on blood-retinal barrier breakdown caused by argon-laser panretinal photocoagulation was evaluated in the rabbit eye. One day before photocoagulation, eyes were given either a sub-Tenon (20-mg) or intravitreal (2-mg) injection of triamcinolone acetonide. The severity of blood retinal barrier breakdown was measured after photocoagulation using rapid sequential magnetic resonance imaging following intravenous administration of gadolinium diethylenetriaminepentaacetic acid. Leakage of gadolinium diethylenetriaminepentaacetic acid into the vitreous space was significantly lower in eyes that received intravitreal triamcinolone acetonide than in control eyes (P = .007); however, sub-Tenon triamcinolone acetonide produced no significant reduction in leakage (P = .65) compared with controls. Fluorescein angiography supported the magnetic resonance imaging findings. We conclude that retinal photocoagulation in the rabbit eye produces blood-retinal barrier breakdown that is partially amenable to corticosteroid treatment. PMID- 1497533 TI - Lipemia retinalis. PMID- 1497532 TI - Photogrammetric analysis of corneal trephination. AB - We used a high-magnification shadow photogrammetric system to evaluate corneal buttons trephined from human donor globes. Whole eyes were trephined with one of five instruments: nonguarded blades held by hand or placed on a handle, Barraquer Mateus motorized trephine, Hessberg-Barron suction trephine, or Hanna microkeratotrephine. Corneoscleral buttons were punched with one of three punches: Cottingham, Katena Lieberman guillotine, or a modified Lieberman guillotine with an increased impact force (BPEI 2). The precision (how closely buttons approximated the trephine diameter), accuracy (repeatability), acircularity (deviation from roundness), and straightness (verticality of edges) of cut were calculated from the diameter and edge profile angle measurements of buttons cut by the different instruments. These results were statistically compared. The Hanna microkeratotrephine instrument had the greatest precision and accuracy, least acircularity, and straightest edges. Of the corneal punches evaluated, the Cottingham instrument had the greatest precision; however, the BPEI 2 punch cut with the greatest accuracy and the straightest edges. PMID- 1497534 TI - Diode endolaser photocoagulation. AB - Endolaser photocoagulation was applied using a diode laser in 25 patients. Indications were for treatment of complications of proliferative diabetic retinopathy (17 patients), proliferative vitreoretinopathy (four patients), complex retinal detachments (three patients), and a retinal break (one patient). Good retinal and retinal pigment epithelial laser uptake was observed in all cases. The clinical appearance of the burn while it is being made is similar to that with the argon laser, but it is subtly lighter, especially in less-pigmented areas and eyes. Predictable clinical results and no adverse effects have been observed. While the clinical utility of the diode laser is analogous to that of standard argon endolaser systems, numerous logistical advantages are offered by this system. PMID- 1497535 TI - A curved, hinged ruler for measurement along the globe. AB - A curved, hinged ruler for measurement along the surface of the globe during strabismus surgery has been designed. A modification of a previously described curved ruler, the current model has a hinge for greater ease of maneuverability and a "T" piece on one end to facilitate measurement and marking of both poles of the muscle without repositioning the ruler. PMID- 1497536 TI - The family caregiver. PMID- 1497537 TI - Support for carers of the ageing: training for leaders of carer groups. PMID- 1497538 TI - The Abbeyfield concept: homes for our independent elderly. PMID- 1497539 TI - Let us not forget our ethnic aged. PMID- 1497540 TI - Validation therapy: a communication link with the confused older person. PMID- 1497541 TI - Behind the wire: nursing in a detention centre. PMID- 1497542 TI - The third age. Personal Care Index for hostel residents. PMID- 1497543 TI - Nurse and the law. Legal commentary on the nurse's role. PMID- 1497544 TI - Healthy ageing. PMID- 1497545 TI - Fluoxetine. PMID- 1497546 TI - Healthy ageing. PMID- 1497547 TI - Normal ageing: a summary. PMID- 1497548 TI - Bilateral adrenal haemorrhage. PMID- 1497549 TI - Outpatient electrophysiological studies. PMID- 1497550 TI - A comparison of Abrams and Raja pleural biopsy needles. AB - The diagnostic yield of the recently developed Raja pleural biopsy needle was compared to that of the Abrams needle. Paired biopsies were obtained in 12 cases. In two cases the Raja yielded a diagnosis of malignancy when the Abrams was negative, and in two other cases (one TB and one leukaemia) the Raja provided more specific diagnostic material. There were no cases where the Abrams provided information not present in a Raja biopsy. In our hands, the Raja pleural biopsy needle gave a diagnostic yield superior to the Abrams needle. PMID- 1497551 TI - The safety and economic advantages of day case electrophysiologic studies. AB - Electrophysiologic Studies (EPS) have been performed as 'day case' procedures in selected patients at Royal Perth Hospital since April 1987. Previously, EPS had involved hospitalisation for two to ten days. During the 51 month period to June 1991, 484 EPS were performed in total. Of these, 153 (105 males and 48 females aged 46 +/- 31y) were day case procedures. Studies were baseline in 60 cases and included drug evaluation in 30. Sixty-one additional studies were performed solely to evaluate therapy. Twenty-one patients required cardioversion. One hundred and fifty one patients were discharged on the same day and two required prolonged observation. The financial cost savings to the hospital for day case EPS is estimated to be $115 per patient and to the community potentially a further $108 per patient. This study demonstrates that in selected patients undergoing elective EPS, day case management is a safe and economic alternative to hospital admission. PMID- 1497552 TI - Co-existence of coeliac disease and insulin-dependent diabetes mellitus in children: screening sera using an ELISA test for gliadin antibody. AB - The prevalence of coeliac disease in children with insulin-dependent diabetes mellitus was investigated using a screening test of serum for antigliadin antibody by ELISA. One hundred and eighty (180) unselected diabetic children were screened for IgA and IgG class antigliadin antibodies (AGA); children with either grossly elevated or slightly elevated AGA had small bowel biopsies. The four children with the highest IgA AGA had total villous atrophy. These four children were considered to have unsuspected coeliac disease. The prevalence of coeliac disease in this group of children was one in 45. Anti-gliadin IgA and IgG tests are suitable for screening children at high risk of having coeliac disease. PMID- 1497553 TI - Reduced synthesis of tissue plasminogen activator by vascular endothelium during acute myocardial infarction. AB - We measured levels of tissue plasminogen activator (t-PA) antigen in 100 patients within six hours of the onset of acute myocardial infarction, in 34 patients with chronic angina but no recent infarction, and in 36 normal subjects. We also assayed von Willebrand factor in the acute patients and in the normal subjects. Measurements were repeated in 40 acute patients at three weeks after myocardial infarction. Although resting levels of t-PA antigen were not significantly different from normal during myocardial infarction, the capacity of the vascular endothelium to release t-PA after five minutes of venous occlusion was impaired (p less than 0.01). The acute phase vessel wall release of von Willebrand factor was increased during acute infarction (p less than 0.01). We conclude that impairment of t-PA production is associated with acute coronary thrombosis, although it is not possible to differentiate between a causative role or a secondary response due to exhaustion of the t-PA producing mechanism. PMID- 1497554 TI - Health service utilisation in the public and private sector by patients with diabetes mellitus aged less than 40 years. AB - This paper uses the Illawarra 0-39 years diabetes register to provide a data base of health service utilisation in the public and private sectors. Eligible patients from the register were divided into a 'stable group' comprising children and adults who had had diabetes for more than one year prior to review and a 'newly diagnosed' group who were followed for one year after diagnosis. The records of inpatient and selected outpatient services at public hospitals as well as visits to general practitioners, paediatricians and physicians were considered. Less than half of all 'newly diagnosed' patients were admitted to hospital for stabilisation and none required readmission in the 12 month review period. Less than one fifth of all 'stable' patients were admitted to hospital during the year. General practitioners were the most frequently used health resource being attended by 31/38 (82%) 'stable children', 122/133 (92%) 'stable adults' and 25/25 (100%) 'newly diagnosed patients'. Public hospital Accident and Emergency Services were the least used health facility being frequented by only 9/38 (24%), 23/133 (17%) and 7/25 (28%) respectively. PMID- 1497555 TI - Recently characterised autoantibodies and their clinical significance. AB - Multisystem autoimmune diseases such as systemic lupus erythematosus (SLE), primary Sjogren's syndrome (SS), scleroderma and polymyositis are characterised by the presence of antinuclear antibodies (ANAs). Immunoblotting and cDNA cloning studies reveal that the autoantigens of the multisystem autoimmune diseases are important proteins involved in nucleic acid metabolism, including tRNA charging, intron splicing, DNA uncoiling, and RNA polymerase co-factors. Each specific syndrome associates with a restricted variety of ANAs, e.g. anti-La with primary SS, anti-Sm with SLE, anti-synthetase enzymes with myositis, anti-topoisomerase 1 (Scl 70) with scleroderma, and anti-centromere with CREST. Precise characterisation of an ANA provides valuable diagnostic and prognostic information, and should be performed when an ANA is detected. PMID- 1497556 TI - Current concepts on monoclonal gammopathies. AB - This is a review of the monoclonal gammopathies, including a discussion of cause. The role of T lymphocytes and B lymphocytes is presented. The recognition of a monoclonal protein in the serum and urine is presented in detail. The frequency of benign and malignant monoclonal gammopathies is provided. A long-term follow up of 241 patients with apparently benign monoclonal gammopathy is examined closely. In this series, multiple myeloma, macroglobulinaemia, amyloidosis, or related disorders developed in 22% of the 241 patients with long-term disease. The median duration from the recognition of the monoclonal protein until the development of serious disease was approximately eight to ten years. The differentiation of benign from malignant monoclonal gammopathies is examined in detail. The point is made that patients must be followed indefinitely because malignancy may develop more than 20 years later. The association of monoclonal gammopathies with other apparently unrelated diseases is discussed. PMID- 1497557 TI - Seizures and giant cell temporal arteritis: what is the relationship? PMID- 1497558 TI - Antibodies against Sarcocystis and Toxoplasma in humans with the chronic fatigue syndrome. PMID- 1497559 TI - Asthma mortality and morbidity. PMID- 1497560 TI - Breast cancer treatment outside teaching hospitals. PMID- 1497561 TI - Successful use of a transdermal nicotine patch to manage a smoker with dementia. PMID- 1497562 TI - Blood ammonia and Helicobacter pylori. PMID- 1497563 TI - Hypokalaemic paralysis induced by bolus prednisolone in Graves' disease. PMID- 1497564 TI - The thermodynamics of psychotherapeutic communication. AB - Given five quantified measures of emotional communication within a psychotherapy session and definitions of work, force and temperature drawn from classical physics, this paper presents calculations of patient and therapist entropy using both the traditional, caloric definition and Shannon's definition, grounded in the work of Boltzmann. Our results depend on the assumption that the patient/therapist system is closed and non-dissipative. We present models for reversible heat absorption and frictional heat dissipation--within the system- which have meaning in emotional communication and psychotherapy. Both calculations of entropy produced a lawful dependence on ln(l+t), where t is time into the session in seconds. The two calculations are essentially the same, verifying in the behavioral domain a law of physics held to be true of material nature. We also verify empirically that the limiting form of the caloric entropy for a purely silent therapist replicates the Shannon entropy for an individual in a monologue. The force field that moves the representations of patient and therapist in 5-dimensional space defines an irreversible process. Thus there are moments of disequilibrium change with respect to the measured variables of emotional communication and at least one moment of disequilibrium between every return to a prior state. This moment may be creative or traumatic. The force field is non-conservative, implying the existence of modalities of heat absorption for patient and therapist which may relate to individual characteristics and reflect human psychological variety. The force field constrains motion to an ellipsoidal shell whose geometry explains the logarithmic growth of Shannon entropy and the finding that the system's absolute temperature grows linearly with respect to time. The finding that the models and methods of physics reveal a degree of lawfulness in the mental/communicative domain as compared to the material speaks strongly for the isomorphic qualities of divergent levels of nature. PMID- 1497565 TI - The myocardium in heart failure: cellular and subcellular alterations in the failing human myocardium. PMID- 1497566 TI - Contractile protein function in failing and nonfailing human myocardium. AB - Isometric heat and force measurements were used to relate mechanical performance to function of contractile proteins in muscle strips from failing and nonfailing human hearts (37 degrees C, 60 beats per minute). Compared to control myocardium, crossbridge behavior was altered in myocardium from hearts with end-stage failing dilated and ischemic cardiomyopathy, resulting in increased crossbridge force time integral by 33% and 36%, respectively. Peak isometric twitch tension was reduced significantly by 46% in muscle strips from hearts with dilated cardiomyopathy. In myocardium from hearts with ischemic cardiomyopathy peak isometric twitch tension was comparable to values from nonfailing hearts. Including all three types of myocardium, there was a close correlation between the number of crossbridge interactions during the isometric twitch (tension dependent heat) and peak twitch tension (r = 0.88; p less than 0.001). Compared to control, in failing myocardium from dilated cardiomyopathic hearts, tension independent heat (calcium cycling) was significantly reduced. This indicates that in dilated cardiomyopathy reduced peak twitch tension results from decreased calcium activation of contractile proteins with reduced number of crossbridge interactions during the isometric twitch. In ischemic cardiomyopathy mechanisms different from those observed in dilated cardiomyopathy seem to be involved in the development of heart failure. PMID- 1497567 TI - Responsiveness of the myofilaments to Ca2+ in human heart failure: implications for Ca2+ and force regulation. AB - Myofilament calcium sensitivity and maximal calcium-activated force are fundamental properties of the contractile proteins in the heart. We examined these properties in normal human right-ventricular trabeculae carneae obtained from hearts of brain-dead patients with no known cardiac disease, and from patients with end-stage heart failure undergoing cardiac transplantation. There were no differences in calcium-activation of the control and myopathic muscles from chemically-skinned trabeculae or from intact tetanized preparations. We then tested the effect of DPI 201-106 (4-[3-(4-diphenylmethyl-1-piperazinyl)-2 hydroxypropoxy]-1H-indole - carbonitrile), a new inotropic agent, in both preparations. In myopathic muscles, 1 microM DPI sensitized the myofilaments to Ca2+, as evidenced by a significant shift of the [Ca2+]-force relationship towards lower [Ca2+], in both skinned and intact preparations. On the other hand, the same concentration of DPI did not affect the calcium-activation in control muscles in both preparations. We also found that the twitch [Ca2+]-force relationship, which has been used as an indication of myofilament sensitivity, was dissociated from the steady-state [Ca2+]-force relationship, and was shifted along the [Ca2+] axis by modulation in the time-course of the twitch and [Ca2+]i, and not by the sensitivity of the myofilaments to Ca2+. Protein kinase C stimulation differentially altered the responsiveness of the myofilaments to Ca2+ in normal and myopathic muscle fibers. We propose that even though calcium activation and maximal calcium-activated force are unaltered in myopathic hearts there are changes in thin filament regulation in myopathic hearts that result in altered responses to agents that directly act on the thin filaments, and that the potential for force development is similar in normal and myopathic human hearts. PMID- 1497568 TI - The regulation of the human beta myosin heavy-chain gene. AB - The human myosin heavy-chain (MHC) genes for cardiac and skeletal muscle exist as a multigene family with eight or more non-allelic genes. Two of them code for the cardiac alpha and beta myocin HCs. They are located on chromosome 14. The skeletal muscle myosin HC genes are on chromosome 17. The cardiac MHCs coexist in the heart, however, with a distinct distribution within cardiac tissue of the human adult. alpha-MHC is predominantly found in the atria and beta-MHC is found in the ventricles. Both genes are also expressed in certain types of skeletal muscle fibers. We have sequenced the beta-gene in its entire length and have further studied in detail its expression in muscle cells. Promoter activities were tested using DNA-mediated gene transfer in cultured chicken embryonic myoblasts. By deletion mapping of the 5' flanking region of the beta-gene a candidate signal sequence was identified in a region which stimulates the promoter in a tissue specific and differentiation dependent mode. The presumed signal was located about 210 bp 5' to the basic promoter which, by itself, is almost inactive, even in muscle cells. The sequence of the signal (CAGCTG) has homology to known E-box sequences. E-boxes (consensus sequence CANNTG) constitute a family of transcription control sites frequently found upstream of muscle genes. In nuclear extracts of cardiac and skeletal muscle (of rabbit) a protein was identified which binds to the region containing the E-box like motif of the beta-gene. Since this protein was present in both types of muscle, overlapping expression control patterns are assumed to operate in these tissues. PMID- 1497569 TI - Contraction frequency dependence of twitch and diastolic tension in human dilated cardiomyopathy (tension-frequency relation in cardiomyopathy). AB - We studied isometric twitch tension and diastolic tension at 37 degrees C as a function of stimulation frequency (12-240 min-1) in very thin (.07-.5 mm2), parallel fibered strips of left-ventricular myocardium. Non-failing control tissue (C) was obtained from epicardial biopsies taken during myocardial revascularization surgery on patients with normal ventricular function. End-stage failing tissue was obtained from endocardial and epicardial biopsies from explanted hearts with idiopathic dilated cardiomyopathy (DCM). The methods and apparatus for biopsy and dissection of myocardium are described. Maximal peak twitch tension at optimal stimulation frequency of 163 +/- 5 min-1 was 41.8 +/- 10 mN/mm2 in non-failing myocardium and it was reduced by 70% (p less than .02) to 12.9 +/- 1.6 mN/mm2 at an optimal frequency of 72 +/- 17 min-1 in DCM. The peaks of the tension-frequency curves occurred at frequencies between 12 and 60 min-1 in most DCM strips (5/9), while in C most of the peaks (8/9) fell between 156 and 180 min-1. The peaks from four DCM hearts fell in an intermediate range of frequencies (96-144 min-1) which also included one non-failing peak at 132 min 1. Diastolic tension declined in both groups as stimulation frequency increased above 12 min-1 and it began increasing when stimulation frequency rose above optimal frequency by 19 +/- 5% and 110 +/- 50% in C and DCM, respectively. Total duration of the isometric twitch diminished with tachycardia remaining shorter than stimulation intervals up to 140 +/- 16 min-1 (3.1 +/- 1 times optimal frequency) in DCM and up to 161 +/- 14 min-1 (not different than optimal frequency) in C. Decline in peak twitch tension above optimal stimulation frequency was 4 to 6 times larger than the accompanying rise in diastolic tension in both groups. The premature decline in tension at lower than normal degrees of tachycardia in DCM does not arise from incomplete relaxation of the twitch response. The 70% deficit in tension generating ability of DCM may be a major contributor to heart failure. Moderate shift in the peak of the tension-frequency curves to lower frequencies (130 min-1) in C does not appear to predispose end stage failure, but it may make the ventricle more susceptible to dilation. PMID- 1497570 TI - Alterations of the force-frequency relationship in the failing human heart depend on the underlying cardiac disease. AB - We investigated the force-frequency relationship (0.5-3 Hz) in non-failing human myocardium and in end-stage failing human myocardium due to dilated cardiomyopathy or subacute myocarditis. In non-failing myocardium, force of contraction increased with increasing stimulation frequency. In end-stage heart failure, the force-frequency relationship was inverse in myocardium from dilated cardiomyopathy, but was similar to control in myocardium from subacute myocarditis. After increasing extracellular Ca(2+)-concentration from 2.5 to 7.2 mM, the shape of the force-frequency relationship was not changed in nonfailing myocardium. In dilated cardiomyopathy, the decline in force with increasing frequencies was even more pronounced at 7.2 mM compared to 2.5 mM extracellular Ca2+. In subacute myocarditis, at Ca2+ 7.2 mM, increasing frequencies increased force in the lower frequency range (less than 1.75 Hz) only, whereas at higher stimulation rates force declined again. These results indicate that (1.) alterations of the force-frequency relationship in the failing human heart depend on the underlying cardiac disease and/or the time-course of the disease, and (2.) an increase in the extracellular Ca(2+)-concentration aggravates changes in the force-frequency relationship in the failing myocardium. PMID- 1497571 TI - Ca(2+)-currents and intracellular [Ca2+]i-transients in single ventricular myocytes isolated from terminally failing human myocardium. AB - The purpose of the present study was to test the hypothesis that steps between the excitation of the cell membrane and contraction are altered in cardiac failure. Ca(2+)-currents and [Ca2+]i-transients were measured in single ventricular myocytes isolated from explanted hearts of patients with terminal heart failure undergoing transplantation, or from donors whose organs could not be used for technical reasons. Peak Ca(2+)-current densities were unchanged, as was the current-voltage relation. However, in myocytes isolated from severely failing hearts resting [Ca2+]i-levels were elevated, peak [Ca2+]i-transients were significantly smaller, and the diastolic decline of [Ca2+]i was markedly slowed. As the trigger for the release of Ca2+ from the sarcoplasmic reticulum is unchanged and the systolic [Ca2+]i-transient is reduced, severe heart failure can be described as partial electromechanical uncoupling. PMID- 1497572 TI - Dynamic calcium requirements for activation of human ventricular muscle calculated from tension-independent heat. AB - The heat and tension generated by strips of human left ventricle taken from nonfailing hearts were measured at 30 C before and after partial inhibition of ATP splitting by the contractile proteins. We used 2, 3-butanedione monoxime (BDM) (4mM) as the chemical inhibition agent and alterations in solution calcium concentration and stimulus frequency to estimate the heat associated with calcium cycling for a wide range of activation levels. Tension-independent heat (TIH) was used to calculate the total calcium cycled per twitch by assuming that two-thirds of TIH was due to ATP splitting by the sarcoplasmic reticulum CA2+ ATPase with a coupling ratio of 2 Ca2+/ATP split and that one-third of TIH was due to ATP splitting by the sarcolemmal Na+ -K+ ATPase supporting the Na+ -Ca2+ exchanger (1 Ca2+/ATP). The enthalpy of creatine phosphate hydrolysis buffering ATP was taken as -34 KJ/mol. There was a highly positive correlation between TIH and mechanical activation during steady-state and nonsteady-state stimulation. The estimated total calcium turnover per twitch at 39% activation (0.3 Hz pacing rate and 2.5 mM Calcium) was approximately 0.17 nmol/g wet weight. This estimate is less than that calculated from biochemical data describing the cellular content and Ca2+ affinity of major Ca2+ buffers, but is similar to values calculated from recent electron probe microanalysis experiments. PMID- 1497573 TI - Factors associated with reactive and reparative fibrosis of the myocardium. AB - Myocardial fibrosis can be defined as an abnormal increase in collagen concentration of either ventricle. This accumulation of collagen, represented predominantly by fibrillar type I collagen, can occur a) on a reactive basis in the interstitial space and adventitia of intramyocardial coronary arteries and does not require myocyte necrosis, or b) as a replacement for necrotic myocytes, where it is considered a scar. Both forms can be found in the same ventricle. Various factors have been found to contribute to the reactive and reparative fibrosis that appears in both ventricles in acquired hypertension. In the case of microscopic scarring, myocyte necrosis is related to catecholamine or angiotensin II- mediated toxicity, reduced potassium stores that accompany chronic mineralocorticoid excess, and coronary vascular remodeling. Reactive fibrosis is associated with elevations in plasma aldosterone concentrations that are inappropriate relative to dietary sodium intake. These findings set the stage for additional in vivo and in vitro studies that may shed more light on our understanding of the factors that regulate the accumulation of fibrous tissue in the myocardium--a major determinant of pathologic structural remodeling which enhances its susceptibility to reentrant arrhythmias and ventricular dysfunction. PMID- 1497574 TI - The extracellular matrix in the failing human heart. AB - The composition of the extracellular matrix was investigated in eight human hearts explanted at the time of transplantation surgery because of endstage cardiomyopathy. All patients showed clinical signs of heart failure. The tissue was investigated by electron microscopy and immunofluorescence microscopy using monoclonal antibodies against collagen I, III, VI, and IV, fibronectin, laminin, and vimentin. All matrix proteins occurred in increased amounts in the extracellular space separating the myocardial cells by septa of enlarged thickness. Laminin and collagen IV surrounded myocardial and endothelial cells as layers of increased thickness. Vimentin localization was normal in individual cells, but occurred more often and corresponded to the numerous fibroblasts as observed by electron microscopy. It is concluded that an excessive deposition of extracellular matrix material in addition to myocyte degeneration (as reported previously (9)) are the structural correlates of cardiac failure. PMID- 1497575 TI - Dysfunction of the ADP/ATP carrier as a causative factor for the disturbance of the myocardial energy metabolism in dilated cardiomyopathy. AB - The adenine nucleotide translocator (ADP/ATP carrier) plays a key role in nucleotide transport across the mitochondrial membrane. The quantity and function of this transport protein were investigated in myocardium from hearts with endstage failing dilated and ischemic cardiomyopathy, and were compared to measurements in nonfailing myocardium. In addition, lactate dehydrogenase (LDH) isoenzymes were determined. The concentration of the ADP/ATP carrier was significantly increased by 48% in myocardium from dilated cardiomyopathic hearts compared to control myocardium. The concentration of the carrier in explanted hearts with ischemic cardiomyopathy did not differ from values in the normal human hearts. Analysis of carrier function revealed similar nucleotide exchange rates in control hearts and hearts with ischemic cardiomyopathy, whereas carrier function was reduced in most hearts with dilated cardiomyopathy. Compared to control hearts, in hearts with dilated cardiomyopathy and decreased nucleotide exchange rate, the carrier content was significantly higher, whereas the carrier content was only slightly increased compared to control in cardiomyopathy hearts with unchanged transport activity. Compared to hearts, in dilated cardiomyopathy there was a significant increase in LDH5 and a decrease in LDH1 isoforms, indicating more anaerobic metabolism in failing dilated cardiomyopathic hearts. In summary, in hearts with dilated cardiomyopathy disturbed function of the ADP/ATP-carrier may result in altered myocardial energy metabolism and, thus, may be the cause of impaired myocardial function. PMID- 1497576 TI - Adenine nucleotide metabolism and contractile dysfunction in heart failure- biochemical aspects, animal experiments, and human studies. AB - In myocardial hypertrophy and heart failure a series of adaptational changes occur some multiplying contractile units, others slowing shortening velocity and increasing economy of contraction. The demonstration of energy-saving mechanisms in heart failure has prompted further investigations of energy providing and utilizing metabolic pathways. The use of myocardial ATP as a substrate occurs mainly at the myosin-ATPase and at the Ca-ATPase of the sarcoplasmic reticulum. As the Michaelis constant of both enzymes for ATP is in the micromolar (microM) range, whereas cellular ATP content is about 5000 microM, these enzymes are not controlled by the availability of ATP as a substrate. In experimental heart failure in large animals, normal or reduced creatine phosphate levels (in most cases together with normal adenine nucleotides) have been described. Reduced creatine phosphate is found in models with increased oxygen consumption, and creatine phosphate may buffer the ATP pool in these models. In human heart failure due to dilated cardiomyopathy, where resting oxygen consumption per unit mass and lactate extraction are normal in most patients, normal adenine nucleotides, creatine phosphate, and mitochondrial function have been described in the initial studies. These results have been challenged by one study showing decreased ATP levels in dilated cardiomyopathy, correlating with the decrease in ejection fraction. However, only ATP has been measured in this study, whereas total adenine nucleotides may be a more suitable parameter. Recently published results have again demonstrated normal ATP and total adenine nucleotides in human heart failure. In the same patients, significantly decreased myocardial norepinephrine was measured, indicating that metabolic changes had occurred in these hearts, but were independent of adenine nucleotides.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1497577 TI - Quantification of Gi alpha-proteins in the failing and nonfailing human myocardium. AB - Heterotrimeric Gi-proteins play an important role in the regulation of cardiac adenylate cyclase. Besides a downregulation of beta-adrenoceptors with an accompanying reduction of the positive inotropic effects of cAMP-dependent positive inotropic agents, an increase of pertussis toxin substrates (Gi alpha proteins) has been observed. The increase of Gi alpha has been reported to be associated with a reduced adenylate cyclase activity in dilated cardiomyopathy from hearts with heart failure class NYHA IV. Since the quantification of Gi alpha-proteins with the pertussis toxin labeling method is hampered by a number of biological and technical factors, Gi alpha-proteins were quantified radioimmunologically using the iodinated C-terminus 125I-KENLKDCGLF as tracer, purified retinal transducin alpha as standard, and an antiserum (DS 4) raised against the same peptide. With this technique Gi alpha-proteins were increased by 118% in dilated cardiomyopathy and 48% in ischemic cardiomyopathy, although pertussis toxin substrates were only increased by 40% in dilated cardiomyopathy and no change was observed in ischemic cardiomyopathy. In cardiomyopathic tissue, an inverse relationship was observed between the increase of Gi alpha and the positive inotropic effects of isoprenaline or milrinone. These data provide evidence for a functional role of Gi alpha in the reduced positive inotropic effects of cAMP-dependent positive inotropic agents. In addition, results obtained with pertussis toxin labeling for quantification of Gi alpha-proteins do not necessarily reflect the expression of Gi alpha-proteins in the human myocardium. PMID- 1497578 TI - Regulation and possible functional implications of G-protein mRNA expression in nonfailing and failing ventricular myocardium. AB - In human end-stage heart failure an increased amount of inhibitory G-protein alpha-subunits (Gi alpha) is assumed to play a role in desensitization of the adenylyl cyclase signaling pathway. In the present study, northern blot experiments with 32P-labeled cDNA probes in ventricular tissue samples from explanted human hearts revealed that Gi alpha-2- and Gi alpha-3- mRNA are the predominant Gi alpha-mRNA subtypes in human ventricles, whereas Gi alpha-1-mRNA was not detectable. The mRNA for the stimulatory G-protein alpha-subunit (GS alpha) consisted of two mRNA sizes. Quantification of mRNA levels revealed a 103 +/- 38% increase in Gi alpha-2-mRNA levels in hearts with idiopathic dilative cardiomyopathy (IDC; n = 8), and a 77 +/- 25% increase in hearts with ischemic cardiomyopathy (ICM; n = 6) as compared to nonfailing controls (NF, n = 8). In contrast, Gi alpha-3- and GS alpha-mRNA levels were similar in failing and nonfailing hearts. To investigate whether or not the increased expression of Gi alpha-2-mRNA might be due to chronically elevated catecholamine levels, we determined the influence of a 4-day infusion of isoprenaline (Iso; 2.4 mg/kg.d), propranolol (Prop; 9.9 mg/kg.d), Iso + Prop or 0.9% NaCl as control (Ctr) on myocardial Gi alpha-mRNA and Gi alpha-protein levels in rats. In Iso-treated rats, hybridization experiments revealed a 49 +/- 18% (n = 7) and 27 +/- 7% (n = 8) increase in Gi alpha-2 and Gi alpha-3-mRNA, respectively. Pertussis toxin catalyzed ADP-ribosylation revealed a 22 +/- 7% (n = 8) increase in Gi-protein as compared to Ctr (n = 8). These alterations were accompanied by an increased potency for the negative inotropic effect (NIE) of carbachol (mean EC50: 0.04 microM vs. 0.28 microM) in the presence of Iso in isolated electrically driven (1 Hz) papillary muscles. Prop itself had no effect, but it antagonized all Iso induced effects. We conclude that, in human heart failure due to IDC or ICM, increased Gi alpha-2-, but not Gi alpha-3- mRNA levels accompany the increased amount of Gi alpha-protein, suggesting that this increase is at least in part due to increased de novo synthesis. The experiments in rats demonstrated that chronic beta-adrenergic stimulation leads to an increased expression of Gi alpha-mRNA and -protein, and to an enhanced potency of the negative inotropic effect of muscarinic agonists.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1497579 TI - [Causes of disease and death in ornamental fish--frequency and importance]. AB - Between 1986 and 1990 1068 aquarium fishes from breeders, wholesale dealers and pet shops and from private owners were examined. In 45% of the cases different non infectious causes of illness or death were detected. Infectious causes were present in 38%. 14% of the fishes showed no pathologic symptoms, whereas 3% of the samples were unfit for examination. The frequency of infectious and non infectious diseases respectively in fishes from breeders vs. dealers vs. private owners is given. From these results factors of pathogenesis in aquarium fishes are discussed and compared to those in fish breeding for food fish. Advices for prevention of diseases in fancy fishes are given. PMID- 1497580 TI - [Autoimmune phenomena during Trypanosoma equiperdum inoculation of the laboratory mouse]. AB - In the course of the Trypanosoma equiperdum-infection of mice an increase of IgM antibodies against the autoantigens dsDNA, keratin and collagen as well as against a protozoan foreign antigen consisting of Sarcocystis gigantea-extract could be observed with a maximum level between 4th and 8th day p. i. The IgG antibodies did not significantly change during the investigation time. A splenomegaly appeared after the infection. The weight of spleen was four times higher than normal. It was suggested that splenomegaly as well as induction of antibodies against several autoantigens and a foreign antigen were due to a polyclonal activation of lymphocytes. PMID- 1497581 TI - [Detection of enterotoxin production in bovine Salmonella isolates]. AB - 54 Salmonella-strains (7 serovars) of bovine origin isolated from faecal samples, rectal swabs as well as from organs of emergency-slaughtered or dead animals were tested for enterotoxin production (heat-labile and heat-stable) in rabbit-ileal loop-assay (RILT), skin-permeability-factor-test (HPT), CHO- and Y1-cell-culture assay and in baby-mouse-test (BMT). The cell-free supernatants (CFS) were used in the tests. The Y1-cells did not respond to the Salmonella toxins. While the RILT was suitable, the CHO-cell-assay proved to be the most sensitive and easy-to handle system. The results confirm the frequent occurrence of the biological property of enterotoxin production within the species Salmonella enterica. Therefore, this property is in our opinion not useful as an epizootological marker for salmonellae. PMID- 1497582 TI - [Infectious causes of pregnancy disorders]. AB - During pregnancy infections can entail disorders in many different ways. Damage through direct transmission of pathogens to the fetus occurs in the first place. The organisms are transmitted transovarially, diaplacentally, via endometrium, before or after implantation, via amnion or by the semen when ascending through the infectious environment. Embryo transfer is a new way of transmission. The respective infective microorganisms either directly colonize in the embryo with the well known consequences (fetotrope pathogens) or they colonize the placenta thus indirectly leading to damages to the embryo (placentotrope pathogens). During the process various overlappings are possible. A second large group of disorders in pregnancy is caused by effects of infections of the mother without pathogens being transmitted to the embryo or the placenta. These diseases are postinfectious allergies, immune complex diseases, damages through microbial toxins or mediators and various other forms of infectious processes found with the mother. The third group of disorders in pregnancy is the result of complications caused by vaccinations of the mother during or shortly before pregnancy: postvaccinal allergies, diseases through vaccinal germs and different other postvaccinal damages or stress because of vaccination. PMID- 1497583 TI - [Bovine colostrum and protection of young animals]. AB - An insufficient absorption of colostrum-immunoglobulins (Ig) by the newborn calf may result in morbidity and mortality at the early age of 1-2 weeks after birth. According to a study from California, such losses amounted to 20% in dairy herds. Ig-deficiencies were observed in almost 90% of all calves which died within the first week of their lives. The rapid identification of Ig-deficient calves, compensation by feeding colostrum from another dam or the application of relevant commercial products from the dairy industry are attempts to remedy such a situation. Feeding bovine colostrum to lambs, kids, foals and piglets, bovine Ig is readily absorbed into the blood-system of these animals. Vaccination of pregnant animals aims at the provocation of specific antibodies for the protection of the offspring. The application of the vaccine into the mammary gland at ablactation provokes specific IgA- and IgM-antibodies which are normally not channelled from the blood system + of the mother into the colostrum. The advantage of the vaccination of pregnant animals is the immediate provision of protecting antibodies for the newborn immuno-incompetent animal. Under the pressure of an increasing criticism against the routinely applied supplementary feeding of antibiotics, this kind of immunization may reach more and more of importance. Like non-specific Igs, specific colostrum-Igs are absorbed into the blood-system of newborns from other animal species. PMID- 1497584 TI - [Characterization of Streptococcus uberis with special consideration of supposed pathogenicity factors]. AB - Streptococcus uberis, as one of the principal causes of bovine streptococcal mastitis, has been characterized serologically and biochemically. Serological grouping of S. uberis revealed polysaccharide antigens of groups E, G, P and U. The biochemical properties of S. uberis, determined with the Strep-Zym identification system, differed clearly from those of S. agalactiae and S. dysgalactiae. Some cultures of S. uberis produced the enzymes hyaluronidase and neuraminidase. In addition S. uberis partly demonstrated CAMP-like synergistic hemolytic activities on sheep blood agar, reacted specifically with the lectins from Helix pomatia and Dolichos biflorus and produced bacteriocin-like inhibitors. This reactions, possibly of importance as virulence factors, as well as "DNA-fingerprinting" of S. uberis, might serve as individual markers of the respective cultures in epidemiological studies. PMID- 1497585 TI - [Mycoplasma bovis-free breeding of cattle]. AB - On a cattle farm latently infected by M. bovis, field studies aiming at the formation of a mycoplasma free herd, were carried out with a group of newborn female calves. These calves were strictly separated from their dams and any other cattle immediately after parturition. Intensive investigations for mycoplasmas were made over 30 months (mycoplasma isolation from nasal swabs, antibody detection by means of indirect hemagglutination test and ELISA technique). M. bovis could never be isolated from the samples. Also, there were no antibodies to M. bovis. In some animals antibody titers to M. bovis occurred after having contact with cattle infected with M. bovis. The results demonstrate a practicable way to establish cattle herds free from M. bovis infection. PMID- 1497586 TI - [The importance of dermonecrotoxin and dermonecrotoxoid of Pasteurella multocida for the calf]. AB - The i. m. application of dermonecrotoxin of P. multocida var. D led to an atrophy of nasal conchae, liver-swelling and to induration of liver and spleen. The intratracheal application caused a lobular pneumonia. The vaccination with toxoid resulted in an immunity against a challenge with toxin but not with P. multocida var. D. Correlations between antitoxic serum-titers and immunity have to be investigated in future. PMID- 1497587 TI - [Salmonella infection sources in poultry flocks in northern Greece]. AB - From 10 egg production poultry farms 1516 samples were collected and examined for the presence of salmonella. The samples were: 201 chicken, 36 sparrows, 35 rats, 35 pools of 20 flies each, 450 eggs, 60 mattresses, 188 feces, 425 feedstuffs and 86 water samples. Salmonellae were isolated only from 163 (10.8%) samples. From the 146 (89.6%) of these S. gallinarum was isolated. From the rest 17 (10.4%) the following mobile salmonella strains were isolated: two strains of S. virchow and Salmonella of subgroup II, four strains of S. typhimurium var. Copenhagen, seven strains of S. Livingstone, one S. enteritidis and one S. infantis The S. gallinarum was isolated from dead or sick chicken (46%), eggs (10.4%), rats Rattus norvegicus (14.3%) and mattresses 1.6%. The mobile salmonellae were isolated from feedstuffs (2%), flies (14.3%), rats (2.8%), feces (1%). From the present study, it seems that rats, chicken and eggs are important for the salmonella dissemination. PMID- 1497588 TI - [Glutathione peroxidase activity in whole blood and plasma of horses of different ages, sexes and different use]. AB - GSH-Px activity in blood and plasma of 269 horses was determined and interrelated to age, sex, and type of use or breed. Furthermore values in blood were related to hematocrit and hemoglobin contents. Trotters and riding horses had higher GSH Px activities in plasma as well as in blood (0.83 +/- 0.22 and 0.79 +/- 0.23 U/ml plasma or 27.2 +/- 4.3 and 24.0 +/- 7.0 U/ml blood) than Thoroughbreds in training and yearlings (0.61 +/- 0.,14 and 0.56 +/- 0.16 U/ml plasma or 20.6 2 +/ 6.9 and 24.6 +/- 4.3 U/ml blood). 3 to 6 years old Thoroughbreds had higher GSH Px-activities than 1 to 2 years old ones. Colts and fillies did not have differing values. PMID- 1497589 TI - Nutrition and cardiovascular risk in Hungary. Introductory lecture. PMID- 1497590 TI - Dietary lipids and coronary heart disease. Epidemiological evidence. PMID- 1497591 TI - Oxygen free radicals, lipid metabolism, and whole blood and plasma viscosity in the prevention and treatment of human cardiovascular diseases. PMID- 1497592 TI - The cholesterol non-consensus. Methodological difficulties in the interpretation of epidemiological studies. PMID- 1497593 TI - Social, psychic and mental factors affecting nutritional behavior. PMID- 1497594 TI - Thirty years GEN 1961-1991. PMID- 1497595 TI - Tribute to past founders of GEN. PMID- 1497596 TI - American experience with nutrition and cardiovascular risks. PMID- 1497597 TI - Nutritional factors correlating with cardiovascular disease: results of the Basel Study. PMID- 1497598 TI - Risk and prevention of coronary heart disease in childhood. PMID- 1497599 TI - Validity of dietary questionnaires in studies on nutrition and heart disease. PMID- 1497600 TI - Nutrition and cardiovascular risk: the biological markers of dietary intake. PMID- 1497601 TI - High-density lipoprotein particles, nutrition and arteriosclerosis. PMID- 1497602 TI - Molecular biological approaches in atherosclerosis research. PMID- 1497603 TI - Proteins and cardiovascular problems. PMID- 1497604 TI - Fat consumption and factor VII coagulant activity. PMID- 1497605 TI - Calreticulin. PMID- 1497606 TI - Activation of lipoprotein lipase in cardiac myocytes by glycosylation requires trimming of glucose residues in the endoplasmic reticulum. AB - Incubation of cycloheximide-treated cardiac myocytes results in a time-dependent increase in cellular and heparin-releasable lipoprotein lipase (LPL) activities. N-Methyldeoxynojirimycin (1 mM) and castanospermine (100 micrograms/ml), inhibitors of glucosidases in the endoplasmic reticulum (ER), prevented the increase in cellular LPL activity. The glucosidase inhibitors did not influence the synthesis or turnover of LPL protein. Therefore activation of LPL by glycosylation in cardiac myocytes requires the trimming of glucose residues in oligosaccharide chains by glucosidases of the ER. PMID- 1497607 TI - Anti-(14-3-3 protein) antibody inhibits stimulation of noradrenaline (norepinephrine) secretion by chromaffin-cell cytosolic proteins. AB - Incubation of digitonin-permeabilized bovine chromaffin cells in the absence of Ca2+ results in a loss of both cytosolic proteins and Ca(2+)-dependent secretion. Addition of these leaked proteins prevents this loss of secretory activity. We have purified a protein from an extract of bovine adrenal medulla which can partially prevent this loss of Ca(2+)-dependent secretion. Antibody against this protein inhibited the ability of leaked chromaffin-cell proteins to prevent the loss of Ca(2+)-dependent secretion. Sequence analysis showed it to have sequence identity with bovine brain 14-3-3 protein. These results demonstrate that 14-3-3 protein makes a significant contribution to the ability of leaked chromaffin-cell proteins to maintain secretory activity. PMID- 1497608 TI - C-terminally truncated human O6-alkylguanine-DNA alkyltransferase retains activity. AB - A cDNA encoding the human O6-alkylguanine-DNA alkyltransferase (ATase; EC 2.1.1.63; methylated-DNA: protein-cysteine methyltransferase) has been manipulated to generate a C-terminally deleted protein which retains full methyl transfer activity. The elimination of 22 amino-acid residues from the C-terminus was achieved by endonuclease-SacI digestion of the 623 bp cDNA coding sequence and ligation of a SacI/HindIII linker containing an in-frame stop codon. The truncated protein was characterized by its reduced molecular mass in immunoblots probed with an antiserum against the full-length protein and by fluorography after incubation with [3H]methylated calf thymus DNA. The rate of methyl transfer was virtually identical for the full-length and truncated ATases. The construction of such a truncated, yet still functional, ATase, with a molecular mass of 19.7 kDa should facilitate a detailed n.m.r. structural study and help to determine the functional significance of the C-terminal domain of mammalian ATases. PMID- 1497609 TI - Uptake of Al3+ into the N-lobe of human serum transferrin. AB - We have studied the binding of Al3+ to human serum apotransferrin (80 kDa) and recombinant N-lobe human apotransferrin (40 kDa) in 0.1 M-sodium bicarbonate solution at a pH meter reading in 2H2O (pH*) of 8.8 using 1H n.m.r. spectroscopy. The results show that for the intact protein, preferential binding of Al3+ to the N-lobe occurs. Molecular modelling combined with an analysis of ring-current induced shifts suggest that n.m.r. spectroscopy can be used to probe hinge bending processes which accompany metal uptake in solution. PMID- 1497610 TI - Yeast transcription factor IID participates in cell-free transcription of a mammalian ribosomal protein TATA-less promoter. AB - We analysed transcription of the gene for the ribosomal protein (rp) L32 of the mouse, which is transcribed in mouse L1210 nuclear extracts in vitro. The rpL32 gene lacks a canonical TATA box. Hence it has been suggested that this gene has an alternative transcription pathway not requiring transcription factor IID (TFIID). Selective inactivation of TFIID in nuclear extract completely abolished the transcription of rpL32 in vitro. Selective inactivation was restored by the addition of cloned and purified yeast TFIID (yTFIID), indicating that this TATA less rpL32 promoter utilizes TFIID for its transcription initiation. Furthermore, addition of an oligonucleotide-containing TATA sequence interfered with the rpL32 transcription and this was overcome by the addition of yTFIID. To further examine the stage of involvement of TFIID in rpL32 transcription, TATA oligonucleotide was added to nuclear extract before and after the formation of the transcription complex. The results reveal that TFIID associates with the pre-initiation complex and that this complex is largely resistant to added TATA oligonucleotide. Our results show, for the first time, that the TATA-less rpL32 gene utilizes TFIID for transcription initiation. PMID- 1497611 TI - Interaction of size-fractionated heparins with lipoprotein lipase and hepatic lipase in the rat. AB - Heparin and heparin partially depolymerized by enzymic digestion were separated into six size fractions. Hep 1 (tetrasaccharides), with a mean M(r) of 1200, did not release significant amounts of either lipoprotein lipase (LPL) or hepatic lipase (HL) on intravenous injection into rats. Hep 2 (mainly octa- and deca saccharides), with a mean M(r) of 2400-3000, released both lipases. To evoke the same plasma activity of LPL and HL required about 10 times more by weight, or about 40 times more molecules, of this heparin than of hep 5 (mean M(r) 12,000, similar to conventional heparin). Hep 5 impeded binding and degradation of 125I labelled bovine LPL by perfused rat livers. In contrast, hep 2 had no detectable effect on these processes. This demonstrates a difference between the sites in the liver that mediate binding, uptake and degradation of LPL, and the extrahepatic sites that bind functional LPL, and the hepatic sites that bind functional HL. After injection of 3.25 mg of hep 5/kg body weight, plasma LPL activity rapidly rose and then remained high for at least 1 h. With hep 2, plasma LPL also rose rapidly, but then decreased to almost basal by 1 h. When a labelled triacylglycerol emulsion was injected 1 h after the heparins, the fractional catabolic rate was enhanced in the rats that had received conventional heparin, as expected from the high plasma LPL activity, but decreased compared with controls in rats that had received hep 2, indicating that available LPL had been depleted through enhanced transport to and uptake in the liver. PMID- 1497612 TI - Suppression by wortmannin of platelet responses to stimuli due to inhibition of pleckstrin phosphorylation. AB - Studies were made of inhibition by wortmannin, a fungal metabolite, of human platelet responses to various stimuli. Wortmannin at concentrations as low as 1 100 nM inhibited several receptor-agonist-induced 5-hydroxytryptamine release from platelets, without affecting agonist-induced increases in the intracellular concentration of Ca2+. Phorbol 12-myristate 13-acetate (PMA), an active tumour promoter, caused 5-hydroxytryptamine release when combined with a low concentration of ionomycin, and platelet aggregation by itself; these effects of the phorbol ester were also inhibited by wortmannin as well as by staurosporine, a potent, although non-specific, protein kinase C (PKC) inhibitor, in a similar molar concentration range. The platelet responses to the receptor agonists or PMA were accompanied by increased incorporation of [32P]Pi into pleckstrin, a protein selectively expressed in platelets and other blood cells arising from haematopoietic stem cells, as a result of PKC activation in the intact cells. The pleckstrin phosphorylation was inhibited by wortmannin in ways mostly similar to those in which it inhibited the 5-hydroxytryptamine-release responses. Nevertheless, wortmannin failed to inhibit PKC activity measurable in a cell-free assay system which is highly susceptible to staurosporine. Nor did it inhibit the translocation of cytosolic PKC to membranes induced by addition of PMA to platelet cells. Thus wortmannin, which is not a direct inhibitor of PKC, could interfere with the kinase-dependent phosphorylation of pleckstrin, which may play an important role in the cellular responses to receptor stimulation. PMID- 1497613 TI - Kinetics of the functional loss of different muscarinic receptor isoforms in Xenopus oocytes. AB - Native Xenopus oocytes express two isoforms of muscarinic receptors that mediate qualitatively different physiological responses. Oocytes of the majority of donors (common) express M3-like receptors (M3Rs) at comparable densities at both the animal and vegetal hemispheres of the cell. Rare (variant) donors possess oocytes that express mainly M1-like receptors (M1Rs), localized predominantly at the animal hemisphere. We have investigated the apparent degradation of these two isoforms and its relationship to their hemispheric distribution. Cycloheximide (CHX) caused a time-dependent decrease in receptor-mediated responses and [3H]quinuclidinyl benzylate (QNB) binding in oocytes from both types of donors. The t1/2 values ranged between 3 and 7 h. Removal of CHX resulted in rapid recovery of the response. This implied rapid degradation and turnover of both types of receptors. The loss of M1Rs was more than that of M3Rs. Moreover, the decrease was more rapid and more extensive on the animal hemisphere in both types of donors. Injection of oocytes expressing either receptor isoform with specific antisense oligonucleotides complementary to either m1 or m3 muscarinic receptors (from mouse) showed receptor loss at approximately the same rate as that calculated from experiments with CHX. Furthermore, oocytes of variant donors express M1Rs exclusively on the animal hemisphere, while the residual activity found on the vegetal hemisphere of the cell was mediated by M3Rs. Inhibition of putative receptor glycosylation with tunicamycin caused a rapid decrease in receptor-mediated responses and radioligand binding on M1Rs, but had virtually no effect on M3Rs. The expression of cloned m1 muscarinic receptors, however, was not affected by tunicamycin, suggesting that glycosylation is not a general prerequisite for the functional expression of muscarinic receptors. PMID- 1497614 TI - Physiological concentrations of 2-oxoglutarate regulate the activity of phosphoenolpyruvate carboxykinase in liver. AB - 2-Oxoglutarate was found to inhibit purified rat liver phosphoenolpyruvate carboxykinase when the assay was performed in the direction of either phosphoenolpyruvate or oxaloacetate synthesis. The inhibition was competitive with respect to oxaloacetate or phosphoenolpyruvate, the Ki values being 0.32 +/- 0.04 mM 0.63 +/- 0.19 mM respectively. 2-Oxoglutarate inhibited non-competitively when tested against GTP or Mn2+. The reported cytosolic concentrations of 2 oxoglutarate in rat hepatocytes are such that the enzyme is likely to be significantly inhibited under basal conditions. The cytosolic concentration of 2 oxoglutarate is known to fall precipitously under the influence of glucagon and other hormones that stimulate gluconeogenesis, and it is suggested that the hormone-induced decrease in 2-oxoglutarate content would alleviate the inhibition of phosphoenolpyruvate carboxykinase and stimulate flux from oxaloacetate to phosphoenolpyruvate. The implications of this finding to the rationalization of the role of pyruvate kinase in the stimulation of gluconeogenesis in the fasted state are discussed. PMID- 1497615 TI - Refeeding meal-fed rats increases lipoprotein lipase activity and deposition of dietary [14C]lipid in white adipose tissue and decreases oxidation to 14CO2. The role of undernutrition. AB - Meal-fed (3 h) rats had a decreased food intake, body weight and carcass fat compared with rats fed ad libitum. On refeeding a chow meal containing [1 14C]triolein, the production of 14CO2 was lower (45%) and the accumulation of carcass [14C]lipid higher (37%) in the meal-fed rats. There was higher lipoprotein lipase activity and greater accumulation of [14C]lipid in the epididymal and subcutaneous adipose-tissue depots of the meal-fed rats. In contrast, heparin-releasable lipoprotein lipase was not increased in perfused hearts of meal-fed rats on refeeding. Return of meal-fed rats to feeding ad libitum reversed these changes before the restoration of body weight or carcass fat. Evidence is presented that decreased dietary intake rather than meal pattern is an important determinant of the alterations in adipose lipid metabolism in the meal-fed rat in response to a meal. PMID- 1497616 TI - The effects of perfluoro-octanoic acid on hepatic peroxisome proliferation and related parameters show no sex-related differences in mice. AB - Male and female C57Bl/6 mice were administered perfluor-octanoic acid PFOA; 0.02 0.05% w/w; 5-10 days) in their diet. This treatment resulted in a several-fold induction of hepatic peroxisomal fatty acid beta-oxidation (monitored as increases in cyanide-insensitive palmitoyl-CoA oxidation, lauroyl-CoA oxidase and catalase activity) in all animals. The protein content of the hepatic mitochondrial fraction was also increased in all mice exposed to PFOA. Furthermore, studies on xenobiotic-metabolizing enzymes revealed no sex-related difference in the response to PFOA. All mice demonstrated a dramatic increase in omega-hydroxylation of lauric acid. Cytosolic epoxide hydrolase, glutathione transferase and DT-diaphorase activities were increased about 2-5-fold. These results with mice differ dramatically from previous studies and our own experiments here with Wistar rats, in which exposure to PFOA causes hepatic peroxisome proliferation in male animals, whereas females are unaffected. PMID- 1497617 TI - Characterization of the ileal Na+/bile salt co-transporter in brush border membrane vesicles and functional expression in Xenopus laevis oocytes. AB - The Na+/bile salt co-transporter of the pig ileal brush border membrane has been expressed in Xenopus laevis oocytes. Injection of pig ileal poly (A)+ RNA into oocytes resulted in the functional expression of an Na(+)-gradient-stimulated taurocholate uptake within 2-5 days. The expressed Na(+)-dependent taurocholate uptake exhibited saturation kinetics (apparent Km of 48 microM), and displayed similar competitive substrate inhibition by taurodeoxycholate as the native brush border Na+/bile salt co-transporter studied in pig ileal brush border membrane vesicles. Interestingly, injection of pig proximal and mid intestinal poly (A)+ RNA into oocytes also resulted in the expression of the Na+/bile salt co transporter, though the Na(+)-dependent transport of bile salts does not occur in brush border membrane vesicles (BBMV) isolated from pig proximal and mid intestine. This suggests that the mRNA coding for the co-transporter is present in the enterocytes lining the whole length of the small intestine, but that the function is only expressed in the brush border of the distal small intestine. The transport of D-glucose into BBMV, and the transport of methyl-alpha-D glucopyranoside (a non-metabolizable hexose derivative) into oocytes were used throughout the study as methods of confirming the integrity of vesicles and oocytes. PMID- 1497618 TI - Structure of a heparan sulphate oligosaccharide that binds to basic fibroblast growth factor. AB - Binding of basic fibroblast growth factor (bFGF) to the extracellular matrix of cultured bovine aorta smooth muscle cells is likely to be mediated via heparan sulphate, since not only exogenous addition of heparan sulphate to the culture medium but also pretreatment of the cells with heparitinase (but not chondroitinase ABC) resulted in loss of binding. Comparison of the affinity of bFGF to various glycosaminoglycan-conjugated gels showed a direct and specific binding of bFGF to heparan sulphate. Heparan sulphate also bound to a bFGF affinity gel. However, the proportion of heparan sulphate bound varied depending on the source of the HS (more than 90% and 45% with pig aorta heparan sulphate and mouse EHS tumour heparan sulphate respectively). The bound heparan sulphate had the ability to protect bFGF from proteolytic digestion, but the unbound heparan sulphate did not. The results suggest the presence in the bound heparan sulphate of a specific structure involved in binding. Limited digestion with heparitinase I of porcine aorta heparan sulphate yielded 13% oligosaccharides bound to the gel, of which the smallest were octasaccharides. Analysis of a hexadecasaccharide fraction which was obtained at the highest yield among the bound oligosaccharides was performed by h.p.l.c. of the deamination products obtained with nitrous acid and the unsaturated disaccharide products formed by heparitinase digestion. Comparison of the disaccharide unit compositions exhibited a marked difference in IdoA(2SO4)GlcNSO3 and IdoA(2SO4)GlcNSO3(6SO4) units between the bound and unbound hexadecasaccharides. The amounts measured were 3 mol and 1 mol per mol of the former and 0.4 mol and 0.6 mol per mol of the latter. It is likely that the binding of bFGF to heparan sulphate may require the domain structure of the heparan sulphate to be composed of clustering IdoA(2SO4) GlcNSO3 units. PMID- 1497619 TI - Inhibition of protein N-glycosylation by 2-deoxy-2-fluoro-D-galactose. AB - The effects of 2-deoxy-2-fluoro-D-galactose (dGalF) on N- and O-glycosylation of proteins was studied in rat hepatocyte primary cultures and in human monocytes. In hepatocytes, dGalF at concentrations of 1 mM or higher completely inhibited N glycosylation of alpha 1-antitrypsin and alpha 1-acid glycoprotein, whereas 4 mM 2-deoxy-D-galactose (dGal) only slightly impaired N-glycosylation. In monocytes, 1 mM- or 4 mM-dGalF blocked N-glycosylation of alpha 1-antitrypsin and of interleukin-6, while O-glycosylation of interleukin-6 remained unaffected. In monocytes, dGal had no effect on protein N-glycosylation. Addition of uridine effectively prevented the UTP deficiency induced by dGalF, but had no effect on the inhibition of protein N-glycosylation by dGalF. Using 19F-n.m.r. spectroscopy, 2-deoxy-2-fluoro-D-galactose 1-phosphate (dGalF-1-P), UDP-dGalF and UDP-dGlcF could be identified as the major metabolites of dGalF in hepatocytes as well as in monocytes. In conclusion, compared with dGal, dGalF is a more efficient inhibitor of protein N-glycosylation. The effect is not caused by the depletion of UTP induced by dGalF, but rather by metabolites of dGalF. dGalF is metabolized not only in hepatocytes but also in peripheral blood monocytes, which can be used for ex vivo studies of disturbances in D-galactose metabolism. PMID- 1497620 TI - Human placental beta-galactosidase. Characterization of the dimer and complex forms of the enzyme. AB - GM1 ganglioside beta-galactosidase (beta-Gal) is deficient in the autosomal recessive disorder GM1 gangliosidosis. A portion of the enzyme occurs in a complex with neuraminidase and an additional glycoprotein, protective protein, but the nature of the interactions conferring the stability of the complex is unknown. Affinity chromatography of beta-Gal on p-aminophenylthiogalactose Sepharose (PATG-Sepharose) at pH 4.3, the pH optimum of beta-Gal, resulted in a 260-fold enrichment of beta-Gal, but the major protein in the fraction had an M(r) value of 74,000. Affinity chromatography on PATG-Sepharose at pH 5.2 showed substantial enrichment (4000-fold) of beta-Gal, and the mature form of the enzyme (M(r) 64,000) was the major protein in the preparation. Using h.p.l.c. molecular sieve chromatography, we found that about 15% of the total beta-Gal occurred in a high-M(r) form (greater than 600,000), the presumptive complex, with 85% eluting at M(r) 150,000, suggestive of a dimer. This distribution was independent of both high (60 mg/ml) and low (5 mg/ml) protein concentration and the pH (pH 4.3 or 5.2) of the sample applied to the column. Furthermore, incubation for 90 min at 37 degrees C, conditions which had previously been suggested as optimal for formation of the complex, had no effect on this distribution. Further fractionation by anion-exchange chromatography and a second affinity column step yielded a beta-Gal preparation that contained a single polypeptide chain (M(r) 64,000), was devoid of neuraminidase and protective protein (absent carboxypeptidase activity), and when injected into rabbits gave rise to monospecific rabbit antisera. We conclude that the protein composition of the complex is variable (i.e. it is different when isolated at pH 4.3 and 5.2) and that the amount of beta-Gal tightly associated with the complex constitutes a small fraction of the total beta-Gal activity. The more prevalent form of the enzyme is a beta-Gal homodimer that is stable and devoid of either neuraminidase activity or protective protein. PMID- 1497621 TI - Characteristics of the beta-galactosidase-carboxypeptidase complex in GM1 gangliosidosis and beta-galactosialidosis fibroblasts. AB - Lysosomal beta-galactosidase (beta-Gal) occurs either alone in monomeric and dimeric forms, or in a high-M(r) complex with at least two additional proteins. One is neuraminidase and the second is the protective protein, which has also been shown to possess carboxypeptidase activity. beta-Gal activity is deficient in GM1-gangliosidosis as a primary defect, and is secondarily affected in galactosialidosis (GS), where the primary defect is the absence of protective protein activity. Fibroblasts from three patients with GM1-gangliosidosis, type 1, showed markedly reduced amounts of beta-Gal cross-reacting material (CRM), and a fourth appeared to have normal levels. A patient with type 2 GM1-gangliosidosis was also found to be CRM-normal. These findings demonstrate that patients with GM1-gangliosidosis type 1 are heterogeneous with respect to the level of residual beta-Gal protein. Fibroblasts from four patients with GS were strongly CRM positive with an anti-beta-Gal antibody, as was a sample of brain from one of these patients, suggesting that the loss of beta-Gal activity is linked to a subtler change in the primary structure of the enzyme than has been previously thought. While three GS cell lines displayed reduced carboxypeptidase activity (to 32-42% of the control), one cell line was completely devoid of activity, demonstrating that while carboxypeptidase activity is a property of the protective protein this action is distinct and separate from its protective role. On direct immunoprecipitation with anti-beta-Gal antibody, a portion of the total carboxypeptidase activity co-precipitated with beta-Gal from extracts of normal and GM1-gangliosidosis cells, consistent with the presence of the complex in these cells. However, no carboxypeptidase activity was precipitable with this antibody from GS fibroblasts, suggesting the absence of complex from these cells. To examine this further, the various forms of beta-Gal were resolved by h.p.l.c. molecular-sieve chromatography. Three forms of beta-Gal activity were resolved in normal cells: a complex, a dimer and a monomer. Residual beta-Gal activity of GS cells resolved into two of these forms, the complex and the monomer. In normal and GM1-gangliosidosis cells a portion of the total carboxypeptidase activity co chromatographed with the complex while the bulk of the activity occurred in a single 36,000-M(r) peak. Only the low-M(r) carboxypeptidase activity was detected in GS cells. This confirms our results on immunoprecipitation indicating that portions of the beta-Gal and the carboxypeptidase activities exist outside the complex in normal, GM1-gangliosidosis and GS cells. In summary, the loss of protective protein function from GS cells results in disproportionate loss of the dimeric and monomeric forms of beta-Gal activity, but does not result in the complete degradation of the protein. PMID- 1497622 TI - Different culture methods lead to differences in glycosylation of a murine IgG monoclonal antibody. AB - A monoclonal IgG-1 was produced by culture of a murine hybridoma (3.8.6) by three different methods, namely culture in ascites, in serum-free media and in serum supplemented media. IgG-1 was purified to homogeneity (as judged by SDS/PAGE under reducing conditions) from each medium by ion-exchange chromatography and h.p.l.c. Protein A chromatography. Oligosaccharides were released from each IgG-1 preparation by hydrazinolysis and radiolabelled by reduction with alkaline sodium borotritide, and 'profile' analysis of the radiolabelled oligosaccharide alditols was performed by a combination of paper electrophoresis and gel-filtration chromatography. This analysis indicated clear and reproducible differences in the glycosylation patterns of the three IgG-1 preparations. Sequential exoglycosidase analysis of individual oligosaccharides derived from each IgG-1 preparation was used to define these differences. Ascites-derived material differed from serum free-culture-derived material only with respect to the content of sialic acid. IgG-1 derived from culture in serum-containing media had an intermediate sialic acid content and a lower incidence of outer-arm galactosylation than the other two preparations. These differences in glycosylation could not be induced in any IgG-1 preparation by incubating purified IgG-1 with ascites or culture medium. It is concluded that the glycosylation pattern of a secreted monoclonal IgG is dependent on the culture method employed to obtain it. PMID- 1497623 TI - Characterization of a tyrosine kinase activity associated with the high-affinity interleukin 2 receptor complex. AB - The IL-2 receptor complex is minimally composed of two genetically unrelated subunits of relative molecular masses 55 and 75 kDa respectively. Structural information deduced from the cDNA sequences of either subunit have not revealed significant information as to the basis of the mechanisms of IL-2 receptor signal transduction. Nevertheless, IL-2 stimulates the activation of one or more tyrosine kinases requiring the functional participation of the p75 member of the receptor complex. Here we have developed the methods to isolate the receptor complex with an associated tyrosine protein kinase. Extracts of membrane glycoproteins from activated normal human T lymphocytes and cell lines demonstrated catalytic activation of tyrosine kinase activity when stimulated with IL-2. Purification of the receptor complex with biotinylated IL-2 revealed the presence of two dominant phosphotyrosyl-proteins of approximate molecular masses 58 and 97 kDa. Denaturation gel electrophoresis followed by renaturation of proteins associated with the IL-2 receptor complex demonstrated that the 97 kDa protein had catalytic autophosphorylation activity. The results indicate that the 58 and 97 kDa phosphotyrosyl-proteins can be found to co-precipitate with the IL-2 receptor complex and that the 97 kDa protein was demonstrated to have protein kinase activity. The association of such kinases with receptors devoid of catalytic structure may represent a unique paradigm of growth-factor receptor mechanisms. PMID- 1497624 TI - Characterization of proteoglycan degradation by calpain. AB - Degradation of cartilage proteoglycans was investigated under neutral conditions (pH 7.5) by using pig kidney calpain II (EC 3.4.22.17; Ca(2+)-dependent cysteine proteinase). Aggregate and monomer degradation reached a maximum in 5 min at 30 degrees C when the substrate/enzyme ratio was less than 1000:1. The mode of degradation was limited proteolysis of the core protein; the size of the products was larger than that of papain-digested products and comparable with that of trypsin-digested products. The hyaluronic acid-binding region was lost from the major glycosaminoglycan-bearing region after incubation with calpain II. Calpains thus may affect the form of proteoglycans in connective tissue. Ca(2+)-dependent proteoglycan degradation was unique in that proteoglycans adsorb large amounts of Ca2+ ions rapidly before activation of calpain II: 1 mg of pig cartilage proteoglycan monomer adsorbed 1.3-1.6 mu equiv. of Ca2+ ions before activation of calpain II, which corresponds to half the sum of anion groups in glycosaminoglycan side chains. This adsorption of Ca2+ was lost after solvolysis of proteoglycan monomer with methanol/50 mM-HCl, which was used to desulphate glycosaminoglycans. Therefore cartilage proteoglycans are not merely the substrates of proteolysis, but they may regulate the activation of Ca(2+) dependent enzymes including calpains through tight chelation of Ca2+ ions between glycosaminoglycan side chains. PMID- 1497625 TI - Solubilization of growth hormone and other recombinant proteins from Escherichia coli inclusion bodies by using a cationic surfactant. AB - Recombinant pig growth hormone (rPGH) was solubilized from inclusion bodies by using the cationic surfactant cetyltrimethylammonium chloride (CTAC). The solubilizing action of CTAC appeared to be dependent on the presence of a positively charged head group, as a non-charged variant was inactive. Relatively low concentrations of CTAC were required for rapid solubilization, and protein bound CTAC was easily removed by ion-exchange chromatography. Compared with solubilization and recovery of rPGH from inclusion bodies with 7.5 M-urea and 6 M guanidinium chloride, the relative efficiency of solubilization was lower with CTAC. However, superior refolding efficiency resulted in final yields of purified rPGH being in the order of CTAC greater than urea greater than or equal to guanidinium chloride. Detailed comparison of the different rPGH preparations as well as pituitary-derived growth hormone by h.p.l.c., native PAGE, c.d. spectral analysis and radioreceptor-binding assay showed that the CTAC-derived rPGH was essentially indistinguishable from the urea and guanidinium chloride preparations. The CTAC-derived rPGH was of greater biopotency than pituitary derived growth hormone. The advantages of CTAC over urea and guanidinium chloride for increasing recovery of monomeric rPGH by minimizing aggregation during refolding in vitro were also found with recombinant sheep interleukin-I beta and a sheep insulin-like growth factor II fusion protein. In addition, the bioactivity of the CTAC-derived recombinant interleukin-1 beta was approximately ten-fold greater than that of an equivalent amount obtained from urea and guanidinium chloride preparations. It is concluded that CTAC represents, in general, an excellent additional approach or a superior alternative to urea and in particular guanidinium chloride for solubilization and recovery of bioactive recombinant proteins from inclusion bodies. PMID- 1497626 TI - Stability of Arthrobacter D-xylose isomerase to denaturants and heat. AB - There was no inactivation of Mg(2+)-containing Arthrobacter D-xylose isomerase up to 1 h in 0-8 M-urea at 22 degrees C, but over this range there was rapid reversible dissociation into fully active dimers with a midpoint around 4 M-urea, as shown by gradient urea gels with an activity stain, and by ion-exchange chromatography and gel filtration in urea buffers. These dimers must have the A B* conformation, since the tetramer could dissociate into A-A*, A-B or A-B* dimer conformations, but only residues across the A-B* interface contribute to the active site. The kinetics of inactivation of the Mg(2+)-containing enzyme in 8 M urea at higher temperatures suggest a partially unfolded Mg-A-B* dimer intermediate with 50% activity, followed by irreversible inactivation coincident with the appearance of unfolded monomer. In 0-4 M guanidinium chloride, a similar reversible dissociation into active dimers occurs, but activity falls, suggesting that A-A* and/or A-B dimers might be part of the mixture. Low concentrations of SDS also give active dimers leading to unfolded monomers, but SDS above 1% (w/v) provides relative stabilization. The apoenzyme is least thermostable (t 1/2 at 80 degrees C, pH 7, = 0.06 h) but Mg2+ stabilizes strongly (t 1/2 = 5.5 h) and Co2+ even more so. Competitive inhibitors or substrates provide a small further stabilization, but this effect is more marked at 80 degrees C, pH 5.5. Together with a marked decrease in optimum pH with temperature, this allows batch isomerizations of glucose under these conditions that produce clean but sweeter syrups. PMID- 1497627 TI - Molecular characterization of a low-molecular-mass matrix metalloproteinase secreted by glomerular mesangial cells as PUMP-1. AB - A polymerase chain reaction (PCR)-based homology cloning strategy was used to define the spectrum of stromelysin-like matrix metalloproteinases (MMPs) synthesized by cultured glomerular mesangial cells (MC). Using this technique, cDNAs encoding an unusual, truncated member of the MMP family, punctuated (putative) metalloproteinase (PUMP-1), were exclusively isolated. Incubation with the cytokines interleukin 1 and tumour necrosis factor increased the abundance of PUMP-1 mRNA in mesangial cells. The mesangial PUMP-1 mRNA is processed in a tissue-specific manner, yielding a transcript containing repeated 3'-untranslated region ATTTA motifs commonly found in cytokines with limited mRNA stability. Polyclonal antibodies prepared against the C-terminal region of the PUMP-1 protein documented release of this enzyme by cultures of cytokine-stimulated MC and permitted identification of PUMP-1-expressing mesangial cells within clinical biopsy specimens of acute glomerulonephritis. These findings represent new molecular and clinical evidence that non-malignant cells process and secrete this unusual member of the MMP family in a cytokine-mediated, tissue-specific manner. Mesangial synthesis of PUMP-1 may contribute to the progression of injury during glomerular inflammatory states. PMID- 1497628 TI - Muller cells of chicken retina synthesize 11-cis-retinol. AB - The amounts of endogenous retinyl palmitate, retinol and retinaldehyde were measured in the neural retina and retinal pigment epithelium (RPE) of predominantly cone (chicken), rod (rat) and more mixed (cat, human) retinae. The ratio of 11-cis to all-trans isomers of retinyl palmitate and retinol in the neural retina and the RPE increases progressively with the increase in diurnality of the species from rat to chicken. The membrane fractions of both chicken and bovine RPE enzymically isomerize all-trans retinol to 11-cis-retinol. Chicken neural retina membranes enzymically form 11-cis-retinol and all-trans-retinyl palmitate from all-trans-retinol. Light and electron microscopy revealed no contamination of chicken neural retina by RPE. Muller cells from chicken retina were isolated, cultured and characterized by immunocytochemical localization of cellular retinaldehyde-binding protein. Cultured chicken Muller cells form all trans-retinyl palmitate, 11-cis-retinol and 11-cis-retinyl palmitate from all trans-retinol and release most of the 11-cis-retinol into the medium. The results indicate that chicken neural retina and Muller cells in particular synthesize 11 cis-retinoids from all-trans-retinol. PMID- 1497629 TI - Cloning, sequencing and characterization of the human alpha glutathione S transferase gene corresponding to the cDNA clone pGTH2. AB - The human Alpha glutathione S-transferase gene corresponding to the human liver cDNA clone pGTH2 was isolated from a cosmid genome library. The gene, represented by the clone cosGTH2, spans nearly 12 kb and contains seven exons. The intron/exon borders conform to the standard rules, and an open reading frame is present, starting at position 67 in exon 2, the double-stop codon being at position 733 in exon 7. Exons 1, 2 and 7 differ in length from the known rat gene coding for the Ya enzyme. A 209 bp 5'-upstream region contains TATA and CAT boxes and, in addition, motifs for Sp1-, NF1- and HNFI-binding factors. Clone cosGTH2 represents the less basic subunit, alpha y, of two Alpha glutathione S transferase subunits (alpha x and alpha y) expressed in liver, which is identical with the kidney subunit alpha 2. PMID- 1497630 TI - Maintenance of total cytochrome P-450 content in rat hepatocyte culture and the abundance of CYP1A2 and CYP2B1/2 mRNAs. AB - mRNAs encoding cytochrome P-450s CYP1A2 and CYP2B1/2 have been quantified in rat hepatocytes cultured for periods up to 72 h under several different culture conditions that maintain total cytochrome P-450 content. When hepatocytes were cultured at either 37 or 30 degrees C in Williams E media, both CYP1A2 and CYP2B1/2 mRNAs declined dramatically. However, when cultured at 30 degrees C for 24 h, the decline in these mRNAs was not as great as that observed in cells grown at 37 degrees C. The addition of dimethyl sulphoxide to cells grown at 37 degrees C did not affect the rate of disappearance of the CYP1A2 or CYP2B1/2 mRNAs. These mRNAs also declined rapidly in cells grown in 'P-450 medium' i.e. RPMI 1640 medium without cyst(e)ine but supplemented with 0.1 mM-delta-aminolaevulinic acid. However, the levels of CYP2B1/2 mRNAs were maintained when hepatocytes were cultured in Williams E medium supplemented with 0.5 mM-metyrapone. These conditions did not, however, maintain the levels of CYP1A2 mRNA. PMID- 1497632 TI - Metabolic control analysis using transient metabolite concentrations. Determination of metabolite concentration control coefficients. AB - The methodology previously developed for determining the Flux Control Coefficients [Delgado & Liao (1992) Biochem. J. 282, 919-927] is extended to the calculation of metabolite Concentration Control Coefficients. It is shown that the transient metabolite concentrations are related by a few algebraic equations, attributed to mass balance, stoichiometric constraints, quasi-equilibrium or quasi-steady states, and kinetic regulations. The coefficients in these relations can be estimated using linear regression, and can be used to calculate the Control Coefficients. The theoretical basis and two examples are discussed. Although the methodology is derived based on the linear approximation of enzyme kinetics, it yields reasonably good estimates of the Control Coefficients for systems with non-linear kinetics. PMID- 1497631 TI - Characterization of the gene celD and its encoded product 1,4-beta-D-glucan glucohydrolase D from Pseudomonas fluorescens subsp. cellulosa. AB - A genomic library of Pseudomonas fluorescens subsp. cellulosa DNA constructed in pUC18 and expressed in Escherichia coli was screened for recombinants expressing 4-methylumbelliferyl beta-D-glucoside hydrolysing activity (MUGase). A single MUGase-positive clone was isolated. The MUGase hydrolysed cellobiose, cellotriose, cellotetraose, cellopentaose and cellohexaose to glucose, by sequentially cleaving glucose residues from the non-reducing end of the cello oligosaccharides. The Km values for cellobiose and cellohexaose hydrolysis were 1.2 mM and 28 microM respectively. The enzyme exhibited no activity against soluble or insoluble cellulose, xylan and xylobiose. Thus the MUGase is classified as a 1,4-beta-D-glucan glucohydrolase (EC 3.2.1.74) and is designated 1,4-beta-D-glucan glucohydrolase D (CELD). When expressed by E. coli, CELD was located in the cell-envelope fraction; a significant proportion of the native enzyme was also associated with the cell envelope when synthesized by its endogenous host. The nucleotide sequence of the gene, celD, which encodes CELD, revealed an open reading frame of 2607 bp, encoding a protein of M(r) 92,000. The deduced primary structure of CELD was confirmed by the M(r) of CELD (85,000) expressed by E. coli and P. fluorescens subsp. cellulosa, and by the experimentally determined N-terminus of the enzyme purified from E. coli, which showed identity with residues 52-67 of the celD translated sequence. The structure of the N-terminal region of full-length CELD was similar to the signal peptides of P. fluorescens subsp. cellulosa plant-cell-wall hydrolases. Deletion of the N-terminal 47 residues of CELD solubilized MUGase activity in E. coli. CELD exhibited sequence similarity with beta-glucosidase B of Clostridium thermocellum, particularly in the vicinity of the active-site aspartate residue, but did not display structural similarity with the mature forms of cellulases and xylanases expressed by P. fluorescens subsp. cellulosa. PMID- 1497634 TI - Calmodulin is involved in catecholamine secretion from digitonin-permeabilized bovine adrenal medullary chromaffin cells. AB - The role of calmodulin in exocytotic secretion was studied using digitonin permeabilized bovine adrenal medullary chromaffin cells. Addition of calmodulin to the permeabilized cells increased Ca(2+)-dependent norepinephrine release in a dose-dependent manner. Unlike calmodulin, addition of caldesmon, actin or bovine serum albumin did not increase the release. Calmodulin increased the release at Ca2+ concentrations of more than 10(-6) M and its effect increased with increase in Mg2+ concentration. Th release of norepinephrine enhanced by calmodulin was inhibited by tetanus toxin, which specifically inhibits exocytotic secretion. These results indicate directly that calmodulin plays an important role in exocytotic secretion from chromaffin cells. PMID- 1497633 TI - Regulation of the mouse liver cytochrome P450 2B subfamily by sex hormones and phenobarbital. AB - The sex-dependent expression and inducibility of the cytochrome P450 2B subfamily was studied in DBA/2 and Balb/c mice, and their F1 recombinants, at the mRNA, protein and activity levels. Analysis of poly(A)+ RNA with specific oligonucleotide probes directed to known mRNAs within the mouse 2B subfamily revealed that the levels of P450 2b-10 and 2b-9 mRNAs were co-regulated with two proteins (56 and 53 kDa) detected by a 2B-specific polyclonal antibody. Other mRNAs related to the 2B subfamily were barely or not at all detectable, and did not coincide with protein expression, suggesting that P450s 2b-9 and 2b-10 are the major 2B isoenzymes present in mouse liver. Specifically, castration of males increased the expression of 2b-9 and 2b-10 mRNAs and protein up to female levels, and testosterone administration to castrated mice reversed these changes. Ovariectomy of females appears to increase the expression of these P450s slightly. 2b-10, but not 2b-9, mRNA and protein were induced by phenobarbital. Based on immunoinhibition studies and the levels of these isoenzymes, P4502b-10 appears to be the major catalyst of 7-pentoxyresorufin O-dealkylation. Both P4502b-9 and P4502b-10 contribute up to 30% of the testosterone 16 alpha hydroxylation, the balance being catalysed by P450s within the 2D subfamily. These experiments show that the female-predominant expression of the two mouse liver isoenzymes P4502b-9 and P4502b-10 is dependent on sex hormones. The fact that P4502b-9 does not respond to phenobarbital, while P4502b-10 is regulated by both phenobarbital and sex hormones, demonstrates the complexity of P450 expression even within one subfamily. PMID- 1497635 TI - Proliferative effect of phospholipase A2 in rat chondrocyte via its specific binding sites. AB - We studied the presence of specific binding sites for pancreatic-type group I phospholipase A2 (PLA2-I), EC 3.1.1.4, and a PLA2-I action on the DNA synthesis of rat chondrocytes. Rat chondrocytes, derived from the xiphisternum of adult rats, had a single class of PLA2-I binding site with an equilibrium binding constant value of 0.9 nM and a maximum binding capacity of 53.9 fmol/10(6) cells. PLA2-I alone did not show any proliferative effect, however, PLA2-I dose dependently stimulated thymidine incorporation in DNA in the presence of basic fibroblast growth factor (bFGF). The mammalian mature type of PLA2s-I specifically recognized the binding sites in these cells and had a synergistic effect on DNA synthesis with bFGF, whereas its inactive zymogen and group II PLA2 showed much lesser activities. The type-specific action of PLA2s implicated the involvement of PLA2-I specific binding sites in this activation process. PMID- 1497636 TI - Effect of photosensitizers in chemical and biological processes: the MTO mechanism in photodynamic therapy. AB - It is suggested that in the course of the application of photosensitizers irradiated for cancer therapy a real competition occurs between the singlet oxygen mediated effects and the interactions between the triplet photosensitizers and doublet radicals formed in tumor cells while processes between photosensitizer radicals and molecules are negligible. This hypothesis is strongly supported by experimental findings and reveals a novel approach for the synthesis of new photosensitizers. PMID- 1497637 TI - Incorporation into planar lipid bilayers of ATP-regulated K+ channels from membranes of the insulin secreting beta-cell line, HIT T15. AB - Ion channels were incorporated into planar lipid bilayers following fusion of vesicles from the membrane of an insulin-secreting beta-cell line, HIT T15. The channel was completely blocked by 0.5 mM ATP. The channel retained the same ATP dependence, voltage-sensitivity and single channel conductance as the ATP regulated K+ channel that found in isolated membrane patches. PMID- 1497638 TI - Analysis of the evolution of angiotensin II type 1 receptor gene in mammals (mouse, rat, bovine and human). AB - The nucleotide and amino acid sequences for mouse angiotensin II (AII) type 1A and 1B receptors were deduced from their complementary and genomic DNAs. Evolutionary analyses based on the nucleotide sequences of the coding region of AII type 1 receptor genes indicated that the duplication event of the type 1 gene occurred 24 +/- 2 million years ago before the divergence between the rat and mouse but after the divergence between rodents and the human/artiodactyls couple. This conclusion was consistent with the results of genomic Southern blot analyses, which revealed that the mouse and rat possess 2 similar but separate genes, whereas the bovine and human have only a single class gene. PMID- 1497639 TI - Nerve growth factor suppresses apoptosis of murine neutrophils. AB - We investigated inhibitory activity of nerve growth factor (NGF) on apoptosis of murine peritoneal exudate neutrophils. During culture for 9 h, apoptotic cells were identified by morphological changes under a light microscope: nuclear pyknosis and chromatin condensation with or without cytoplasmic vacuolation. The apoptotic state was confirmed by DNA fragmentation indicating the endogenous endonuclease activation. When neutrophils were incubated in the presence of NGF, the proportion of cells with the morphological changes was decreased in a dose dependent manner, and the development of the characteristic DNA fragmentation was restricted. The apoptosis-suppressing activity of NGF was abolished by the addition of anti-NGF monoclonal antibody. These results suggest that NGF may suppress neutrophil apoptosis by preventing the endogenous endonuclease activation. PMID- 1497640 TI - Small-angle X-ray scattering study by synchrotron orbital radiation reveals that high molecular weight subunit of glutenin is a very anisotropic molecule. AB - Small-angle X-ray scattering of one high molecular weight (HMW) subunit of wheat glutenin was measured at protein concentration ranges from 1.0 to 10.0 mg/ml. The radius of gyration of whole particles, RO, in aq. 50% (v/v) 1-propanol and 0.1M acetic acid was 16.6 +/- 0.1nm and 22.8nm, respectively, and the corresponding radius of gyration of the cross-section, RC, was 2.82 +/- 0.02 nm and 2.23 +/- 0.01 nm, which indicate that the glutenin HMW subunit exists as very anisotropic particles in both solutions. The RO and RC values of the subunit, and the drastic decrease in scattered intensity at small angles that occurs in the acetic acid solution with relatively low protein concentration are completely explained in terms of rod-like molecules of the glutenin HMW subunit. PMID- 1497642 TI - Characterization of human thyrotropin receptor-related peptide-like immunoreactivity in peripheral blood of Graves' disease. AB - An antiserum raised against an alignment of amino acid-(32-56), termed TSHRP-1, in the extracellular domain of human thyrotropin (TSH) receptor was used to identify the TSH receptor-like substance in plasma of Graves' disease. The dilution curve of plasma TSHRP-1-like immunoreactivity was observed in a manner parallel to the standard synthetic peptide curve in radioimmunoassay, and its molecular weight estimated approximately 60 kDa. The amounts of TSHRP-1-like immunoreactivity were significantly higher in Graves' plasma than those in plasma of normal and hypothyroid patients due to Hashimoto's thyroiditis. The present results indicate that human peripheral blood possesses a soluble form of the extracellular domain of TSH receptor which may contribute to the pathophysiology of Graves' disease. PMID- 1497641 TI - Establishment of hypersensitive radioimmunoassay for islet amyloid polypeptide using antiserum specific for its N-terminal region. AB - Using a synthetic N-terminal hexadecapeptide of islet amyloid polypeptide (IAPP), we prepared an antiserum specific for IAPP[1-16] and established an extremely sensitive radioimmunoassay (RIA) for the peptide with a minimum detection level of 0.26 fmol/tube. Since the N-terminal sequence of IAPP is 100% conserved in many mammalian species, the RIA is widely applicable in quantifying their IAPP. Analyses of pancreatic extracts of human and hamster using reverse-phase high performance liquid chromatography coupled with the RIA revealed that almost all pancreatic IAPP consisted of IAPP[1-37]. On the other hand, rat and mouse pancreata contained substantial amounts of IAPP[1-16] and IAPP[1-17] in addition to IAPP[1-37] as a major molecular form. In human plasma, IAPP[1-37] is the major molecular form secreted into the circulation in response to glucose administration. The RIA established in this study is promising in elucidating the physiological functions and the pathophysiological significance of IAPP in diabetes mellitus. PMID- 1497644 TI - pH dependent conformational changes in the T- and R-states of insulin in solution: circular dichroic studies in the pH range of 6 to 10. AB - Zinc insulin hexamer has been shown to undergo a phenol-induced T6 to R6 conformational transition in solution. Our circular dichroic (CD) studies demonstrate that insulin undergoes pH-dependent conformational changes over the pH range of 6-10 in the T-state and in the R- state. In order to determine which specific amino acid residues may be responsible for these pH-dependent changes, a series of insulin analogs were utilized. In the T-state, the pH dependent CD changes monitored in the far UV region have a pK of 8.2 and appear to be related to the titration of the A1-Gly amino group. Using the near UV CD a second pH dependent conformational change was detected with a pK of 7.5 in the T-state. 1H N.M.R. studies suggest that B5-His may be responsible for this conformational transition. In the presence of m-cresol (R-state), the pK value was found to be 6.9. During this titration, the increased ellipticity for the R-state is diminishing as pH decreases from pH 8 to 6, and no difference in ellipticity was observed at 255 nm between T- and R-states at pH 6. Therefore, this may be due to the transition from the R back to the T-state. PMID- 1497643 TI - Phosphorylation of the recombinant spliced variants of the alpha-sub-unit of the stimulatory guanine-nucleotide binding regulatory protein (Gs) by the catalytic sub-unit of protein kinase A. AB - Both GS alpha-1 and GS alpha-4 were phosphorylated by the purified catalytic sub unit of protein kinase A. Phosphate incorporation into 220 pmol and 190 pmol of GS alpha-4 and GS alpha-1 after a 1 hour incubation with kinase was 14 pmol and 10 pmol, respectively. These low levels of phosphorylation are due to the thermal lability of purified recombinant GS alpha. However, the phosphorylation was inhibited by guanine nucleotides (GDP-beta-S, GppNHp and GTP) and is, therefore, a specific event. We suggest that, as for GS alpha phosphorylation by protein kinase C (Pyne et al., 1992), the guanine nucleotide-free form of GS alpha is the most likely substrate. Guanine-nucleotides reduce the lifetime and, therefore availability for phosphorylation, of guanine-nucleotide free GS alpha. GS alpha phosphorylation by protein kinase A in vitro provides preliminary evidence that a similar phosphorylation of GS alpha may be an important regulatory event in cells. PMID- 1497645 TI - Effect of pH on quercetin-induced suppression of heat shock gene expression and thermotolerance development in HT-29 cells. AB - When cells were heated for 15 min at 45 degrees C, they became thermotolerant to a second heat exposure at 45 degrees C. Thermotolerance developed rapidly, reached its maximum 6 hr after heat shock, and then gradually decayed. The development of thermotolerance was partially suppressed by treatment with various concentrations of quercetin (0.05-0.2 mM) at pH 7.4 after the initial heat treatment. In contrast, the drug markedly inhibited thermotolerance development at pH 6.5. Furthermore, a combination of low pH and quercetin treatment distinctively altered the expression of HSP70 gene compared with that of HSP28 or HSP90 gene. These results demonstrate a good correlation between the amount of HSP70 gene expression and development of thermotolerance. PMID- 1497646 TI - Detection of the GLUT3 facilitative glucose transporter in rat L6 muscle cells: regulation by cellular differentiation, insulin and insulin-like growth factor-I. AB - The GLUT3 facilitative glucose transporter protein was found to be expressed in rat L6 muscle cells. It was detected at both the myoblast and myotube stage. GLUT3 protein content per mg of total membrane protein increased significantly during L6 cell differentiation. Subcellular fractionation demonstrated that the GLUT3 protein was predominantly localized in plasma membrane-enriched fractions of either myoblasts or myotubes. Short-term exposure of L6 myotubes to IGF-I or insulin caused a redistribution of GLUT3 protein from an intracellular membrane fraction to the plasma membrane, without affecting total membrane GLUT3 protein content. Long-term exposure of L6 myotubes to IGF-I produced an increase of GLUT3 protein in total membranes and all subcellular membrane fractions, especially the plasma membrane. We propose that the GLUT3 glucose transporter may play an important role in glucose metabolism in developing muscle. PMID- 1497647 TI - High level expression, purification, and characterization of the Kunitz-type protease inhibitor domain of protease nexin-2/amyloid beta-protein precursor. AB - The protease inhibitor, protease nexin-2 (PN-2), is the secreted isoform of the Alzheimer's amyloid beta-protein precursor (A beta PP) that contains the Kunitz type protease inhibitor (KPI) domain. Here we describe the use of the methylotrophic industrial yeast Pichia pastoris as a host system for the large scale production of the KPI domain of PN-2/A beta PP. In addition to the 57 amino acid KPI domain, the expression product contained an additional four amino acid residues at its amino terminus that correspond to amino acids 285-288 of A beta PP (Ponte et al. 1988 Nature 311:525-527). This expression system generated yields of greater than 1.0 gram of KPI domain per liter of fermentation media. The secreted 61 amino acid product was purified to homogeneity and biochemically characterized. Amino acid analysis and sequencing of the entire expressed KPI domain verified its integrity. Similar to native PN-2/A beta PP, the purified KPI domain potently inhibited trypsin, chymotrypsin, and coagulation factor XIa. Although heparin augments the inhibition of factor XIa by native PN-2/A beta PP it had no effect on the inhibition of factor XIa by expressed KPI domain suggesting that heparin binds to regions on native PN-2/A beta PP outside of the protease inhibitory domain. This KPI domain expression product should be useful in studying the physiologic and pathophysiologic functions of PN-2/A beta PP. PMID- 1497648 TI - Rhamnose moiety of phosphoramidon is not required for in vivo inhibition of endothelin converting enzyme. AB - Experiments were conducted to determine the importance of the carbohydrate moiety of phosphoramidon in the inhibition of the pressor response to big endothelin-1 in anesthetized rats. Big endothelin-1 produced a 42% increase in mean arterial pressure which was nearly abolished by co-infusion of phosphoramidon. Similarly, when an analog of phosphoramidon lacking the rhamnose group (phosphoryl-leu-trp OH) was co-infused, a significant attenuation of the pressor response was observed. These findings indicate that the rhamnose moiety of phosphoramidon is not responsible for the distinguishing this compound as an inhibitor of the response to big endothelin-1 in the rat. PMID- 1497649 TI - The generation of inositolglycan mediators from rat liver plasma membranes: the role of guanine nucleotide binding proteins. AB - The guanine nucleotide dependence for the generation of inositolglycan second messengers from rat liver plasma membranes has been investigated. Plasma membranes, when treated with insulin release a soluble mediator substance which activates pyruvate dehydrogenase (PDH). Guanosine 5'-[3-thio]triphosphate (GTP gamma S) was found to be as potent as insulin in stimulating mediator release. The stimulatory effects of GTP gamma S required the presence of magnesium and following preincubation of membranes with guanosine 5'-[2-thio]diphosphate (GDP beta S) the stimulation of mediator release by either insulin or GTP gamma S was blocked. The activation of PDH by mediator fractions produced in response to either insulin or GTP gamma S was abolished following treatment of the fractions with anti-inositolglycan antibodies. The significance of these observations with respect to the possible involvement of a regulatory guanine-nucleotide binding protein (G-protein) in the generation of insulin mediators is discussed. PMID- 1497650 TI - Correlation between up-regulation of lymphokine mRNA and down-regulation of TcR, CD4, CD8 and lck mRNA as shown by the effect of CsA on activated T lymphocytes. AB - Full activation of different T cell populations via the TcR/CD3 complex leads to transient expression of lymphokine mRNA and to transient and specific down modulation of TcR, CD4, CD8 and p56lck mRNA (Multi-Receptor Complex or MRC mRNA). This transient down-modulation is due to both a decrease in transcription and stability of these mRNA and is temporally and quantitatively related to lymphokine mRNA induction. We showed that cyclosporin A (CsA), which blocks lymphokine expression also inhibits MRC mRNA down-modulation at the transcriptional level, and does not affect mRNA stability. The fact that CsA inhibits both lymphokine expression and MRC mRNA down-modulation at transcriptional level supports a model in which similar signals trigger the inverse regulation of these two sets of genes via identical transcriptional factors. PMID- 1497651 TI - Hydrogen/deuterium isotope effect in the oscillating peroxidase-oxidase reaction. AB - The oscillatory peroxidase-oxidase reaction has been investigated by using NADH deuterated in the nicotinamide 4-A position. A considerable kinetic hydrogen/deuterium isotope effect on the oscillatory behavior was revealed, which may provide an additional valuable tool for mechanistic studies and for discriminating between various mechanistic models of the peroxidase-oxidase reaction. Particularly, this effect manifests in different oscillation frequencies. A sequence of simple and aperiodic oscillations was found between two stable steady states. PMID- 1497653 TI - Proteolytic machinery of glomerular epithelial cells against IgG. AB - Accumulation of immune complexes in the subepithelial region of the glomerular basement membrane results in the lesion of membranous nephropathy. The inefficient handling of immune complexes by the glomerular epithelial cell was investigated by studying the mechanism of IgG proteolysis by the intracellular proteases of cultured epithelial cells. Radiolabelled IgG was incubated with extracts of cells and the digestion of IgG was monitored by SDS-PAGE analysis. Prolonged incubation of IgG with the cell extracts resulted in only partial degradation of the IgG. The enzyme responsible for the breakdown was determined to be the lysosomal cathepsin D based on the pH optimum and the presence of aspartate in the active site of the enzyme. SDS-PAGE analysis of the digestion fragments revealed that a large proportion of the incompletely degraded IgG was the (Fab)2 fragment, which was resistant to further proteolysis. This could be one of the possible explanations for the slow removal of IgG from the subepithelial location of the basement membrane. PMID- 1497652 TI - Glycation of lens MIP26 affects the permeability in reconstituted liposomes. AB - We studied the role of glycation of lens putative gap junctional protein, MIP26, on the permeability as well as on calmodulin mediated gating activity in reconstituted liposomes. Calf lens membranes were incubated with 0-100 mM glucose for 3 days and MIP26 was isolated. There was a glucose concentration dependent increase in the glycation of MIP26 which reached to 2.48 moles/mole of protein with 100 mM glucose. Gel electrophoresis showed that there was no degradation of MIP26 to MIP22 during incubation. Channel permeability was determined by reconstituting MIP26 into asolectin liposomes. There was a MIP26 glycation dependent decrease in the permeability to sucrose. Furthermore, proteoliposomes containing nonglycated MIP26 showed complete uncoupling of the channels with calmodulin whereas the channels containing glycated MIP26 were only partially uncoupled. These results suggest that glycation of MIP26 does interfere with the gating activity in reconstituted liposomes. PMID- 1497654 TI - Low-affinity Ca(2+)-binding sites versus Zn(2+)-binding sites in histidine-rich Ca(2+)-binding protein of skeletal muscle sarcoplasmic reticulum. AB - Histidine-rich Ca(2+)-binding protein (HRC) is a 170 kDa protein that can be identified in the isolated sarcoplasmic reticulum from rabbit skeletal muscle by its ability to bind [125I]low-density lipoprotein on blots after SDS-PAGE and that appears to be bound to the junctional membrane through calcium bridges. Molecular cDNA cloning of this protein predicts the existence of a Ca(2+)-binding domain and of a distinct heavy-metal binding domain at the cystein-rich COOH terminus. Here we demonstrate, using radioactive ligand blot techniques, that HRC protein binds 45Ca at low affinity, as well as being able to bind 65Zn, but at different sites, that are largely inhibitable by prior reductive alkylation of the protein. In contrast to Ca(2+)-binding protein calsequestrin not having detectable 65Zn-binding sites, HRC protein bound selectively to immobilized Zn2+ on IDA-agarose affinity columns. Our results also indicate that rabbit and human 140 kDa HRC protein have common properties. PMID- 1497655 TI - Calreticulin is present in the acrosome of spermatids of rat testis. AB - We have already succeeded in purifying a calcium-binding protein (CalBP) from rat spermatogenic cells [Nakamura et al., Biochem. Biophys. Res. Commun., 176 (1991) 1358]. In this study, the location of this protein within rat testis was examined, using a rabbit antisera for this protein. The antigen was localized on the developing acrosomes during spermiogenesis. The NH2-terminal amino acid sequence obtained for rat CalBP was identical to that of calreticulin obtained for the skeletal muscle of mice and closely resembled that for rabbit calreticulin. On the immunoblot analysis, the purified rat CalBP reacted with an antibody raised against rabbit skeletal muscle calreticulin. The results indicate that calreticulin is present in the acrosome of spermatids of rat testes. PMID- 1497656 TI - The regulation of the intracellular sodium ion concentration in cultured chick embryo heart cells. AB - Using digital imaging microscopy with the fluorescent indicator sodium-binding benzofuran isophtalate, we examined the cytosolic Na+ concentration ([Na+]i) in individual chick embryo heart cells. Inhibition of the Na(+)-H+ exchanger using Na(+)-free (Li+ substituted) medium and inhibition of the Na(+)-efflux through the Na(+)-Ca2+ exchanger using Ca(2+)-free medium didn't change the [Na+]i. The opening of voltage-dependent Na+ channels with veratridine (150 micrograms/ml) and inhibition of the Na(+)-K(+)-Cl(-)-cotransporter with bumetanide (10 microM) led to an increase in [Na+]i by 107% and 86%, respectively, suggesting that the Na+ channels and the Na(+)-K(+)-Cl- cotransporter predominantly regulate the [Na+]i in cultured chick embryo heart cells. PMID- 1497657 TI - Identification of the iron-binding histidine residues in soybean lipoxygenase L 1. AB - Lipoxygenases constitute a class of non-heme, non-sulfur iron dioxygenases acting upon lipids possessing a 1,4-cis-cis-pentadiene moiety. The iron is known to be essential for activity. A motif of six histidine residues has been found in all of the thirteen lipoxygenases, from both plant and animal sources, whose sequences have been reported. We had previously obtained mutant proteins in which each of the 6 conserved histidines of soybean lipoxygenase L-1 had been replaced and found that the mutants H499Q, H504Q (or H504S) and H690Q had no detectable enzymatic activity. We have now found that these inactive proteins contain no Fe, although they have the same electrophoretic mobility as wild-type L-1 under both denaturing and non-denaturing conditions and react with anti-L-1 antibodies. PMID- 1497658 TI - Quinone dependent NADH dehydrogenation in mitochondria-like particles from Setaria digitata, a filarial parasite. AB - In the cattle filarial parasite, Setaria digitata, the mitochondria-like particles have been shown to possess site I associated oxidative phosphorylation and rotenone sensitive and insensitive pathways for the dehydrogenation of NADH. Quinone depleted mitochondria-like particles show a loss of activity of these NADH dehydrogenases and also a complete loss of fumarate reductase activity. Reconstitution with quinone restores both NADH linked oxygen uptake and fumarate reductase activity. Thus activities of complex I and fumarate reductase are linked to quinone. Hence an inhibitor at the level of quinone can simultaneously block both aerobic and anaerobic pathways which drive ATP production and may prove useful in the effective control of filariasis. PMID- 1497659 TI - Transactivation of the human c-myc gene by c-Myb. AB - We analyse the contribution of six Myb-binding sites in the upstream c-myc sequences to transactivation by co-transfection assays. Surprisingly, deletion of the six Myb-binding sites did not influence the transactivation of c-myc by c-Myb protein. Instead, the strongest transactivation was observed with a c-myc reporter plasmid which contains only 450 bp of exon 1 including the c-myc promoter P2. An exchange of the DNA binding domain of c-Myb by that of GAL4 led only to small transactivation effects indicating that the DNA binding domain of c Myb is essential for transactivation of the c-myc gene. These results suggest either an indirect transactivation mechanism of the c-myc gene by c-Myb proteins or a role of the DNA binding domain for additional effects than DNA binding. PMID- 1497660 TI - Identification of four genomic loci highly related to casein-kinase-2-alpha cDNA and characterization of a casein kinase-2-alpha pseudogene within the mouse genome. AB - Using the coding region of the human CK-2 alpha cDNA as a probe for screening a genomic mouse library, positive clones representing four different genomic loci were isolated. Partial DNA sequences of these loci encompassing the first 120 nucleotides of the putative coding region are reported. One positive clone was further analyzed by sequencing a 3.1 kb XbaI fragment. This clone displays the characteristics of a pseudogene, i.e. lack of introns and several nucleotide insertions and deletions. In its 3' region it contains a 91 bp large CT-rich stretch which consists of (CCTT) and (CT) repeats; in the 5' region three (CCCCCT) repeats. PMID- 1497661 TI - Purification and properties of a functional 47-kilodalton cytosolic factor required for NADPH-oxidase activation in bovine neutrophils. AB - A cytosolic factor of 47 kDa required for activation of the NADPH oxidase, and referred to as p47, has been purified in its functional form from the cytosol of resting bovine neutrophils. The purification was monitored by the determination of the activating potency of p47 in a cell-free system of oxidase activation. The recovery was around 10% and the purification factor greater than 1000. P47 was phosphorylated in vitro by protein kinase A and protein kinase C. [32P] labeled p47 was resolved by isoelectric focusing into two major labeled bands of pI 7.0 and 8.5. Polyclonal antibodies were used to demonstrate that p47 is localized specifically in the cytosol of resting neutrophils, and that, upon activation of neutrophils, p47 is translocated from the cytosol to the membrane. PMID- 1497662 TI - Functional characterisation of serum DNase I in MRL-lpr/lpr mice. AB - The autosomal defect in Fas antigen leads CD4-CD8-T-cells to accumulate in lymph nodes and spleen of MRL-lpr/lpr mice. MRL-lpr/lpr mice present increased levels of DNase I as compared to the control strain MRL-+/+. This DNase I, which most probably originates from the accumulated CD4-CD8-T-cells, cleaves nuclear DNA with a strong preference for internucleosomal sites yielding, in the presence of both Ca2+ and Mg2+, a pattern of fragments typical for apoptosis. Furthermore, we show that this "apoptosis-ladder" can be obtained with purified DNase I in presence of normal serum. PMID- 1497663 TI - A mathematical approach to lipolysis based on the interrelationship of physicochemical and biochemical data. AB - A novel approach is described for the quantitation of the parameters involved in lipolytic activity. The activity of lipase purified from human pancreatic juice against an oil-water emulsion depends on the degree of emulsification, the type of emulsifier used, the type and the concentration of bile salt, the concentration of colipase and, finally, on the zeta-potential of the interface. The zeta-potential, in turn, depends on the partition of bile salt molecules between the micellar state in the bulk and their adsorption on the oil-water interface. None of these parameters correlates straightforward with lipase activity. However, if several parameters are taken into account, the enzyme activity determined in our system obeys a multiparametric equation where the variables are: the conjugation of bile salts, the number of hydroxy groups, their aggregation number and, finally, the zeta-potential of the oil droplets. PMID- 1497665 TI - Evaluation of nitrite production by human monocyte-derived macrophages. AB - Reactive nitrogen intermediates are important in the anti-tumor and anti microbial activities of rodent macrophages, but it is not known whether this is the case for human macrophages. In the present study, nitrite concentrations in vitro were used as an indicator of reactive nitrogen intermediate production by mouse, rat, and human macrophages. Human macrophages derived by culturing peripheral blood monocytes did not consistently produce detectable nitrite levels in response to any stimulus examined. Human macrophages were viable and metabolically active as indicated by the MTT assay, and their respiratory burst response to phorbol myristate acetate was increased following incubation with Interferon-gamma, as expected for typical macrophages. In contrast, rat or mouse peritoneal macrophages produced nitrite concentrations of approximately 20-100 microM in response to lipopolysaccharide, Interferon-gamma, or both. These results demonstrate substantial differences in the production of nitrites by rodent and human macrophages. Because of the heterogeneity among macrophage populations, these findings may not be applicable to all human macrophage populations, but they suggest a need for caution in extrapolating from rodent studies regarding the role of reactive nitrogen intermediates in anti-tumor or anti-microbial functions of human macrophages. PMID- 1497664 TI - Human preproendothelin-1 is converted into active endothelin-1 by baculovirus infected insect cells. AB - To investigate biochemical and biological parameters involved in preproendothelin 1 (preproET-1) maturation we infected Spodoptera frugiperda (Sf21) cells with a suitable engineered baculovirus vector carrying the cDNA encoding the entire human 212 amino acids precursor. Culture supernatants were tested by RIA using an anti-ET-1 serum, ET-1-like immunoreactive material (IRM) was detected in the infected Sf21 cells but not in control, wild-type or mock-infected cells. Fractionation of the culture supernatant by RP-HPLC coupled to an ET-1 specific RIA yielded two main peaks corresponding to the retention times of human bigET-1 and ET-1. Furthermore, culture supernatant of preproET-1 expressing Sf21 cells elicited a characteristic dose-response vasoconstrictive activity on rabbit vena cava, consistent with the amount of ET-1 as estimated by RP-HPLC coupled to RIA. These results suggest that insect cells possess the enzymatic activities necessary for human preproET-1 full maturation even though no such peptide has ever been found in insect cells. PMID- 1497666 TI - Purified estrogen receptor enhances in vitro transcription. AB - An in vitro transcription system was developed to investigate the mechanisms of gene regulation by the estrogen receptor (ER). ER purified from calf uterus was highly active in enhancing RNA transcription from a template DNA containing estrogen response elements (EREs) upstream from a minimal promoter. Under the conditions employed, no addition of tissue specific factors was required and both estrogen or antiestrogens were ineffective. The stimulation of transcription correlated with the copy number of EREs in the template. The addition of competitor ERE oligonucleotides specifically inhibited the ER-induced transcription. We suggest that the ER may be involved in the formation of the stable initiation complex. PMID- 1497667 TI - Signal peptide for peroxisomal targeting: replacement of an essential histidine residue by certain amino acids converts the amino-terminal presequence of peroxisomal 3-ketoacyl-CoA thiolase to a mitochondrial signal peptide. AB - The role of the histidine residue at position -17 of the amino-terminal signal peptide of rat peroxisomal 3-ketoacyl-CoA thiolase was studied in vivo, employing site-directed mutagenesis. Among the nine amino acids tested, only glutamine could partially substitute for the histidine. Mutants carrying basic amino acids, arginine and lysine, and hydrophobic residues, leucine and valine, in place of histidine were all translocated to mitochondria, but not to peroxisomes. These results indicate that the signal peptide of the thiolase is recognized by a mechanism totally different from that for the SKL motif, a known peroxisomal targeting signal. Relationship of the thiolase signal peptide to those of mitochondrial proteins is discussed. PMID- 1497669 TI - Protein transport in the permeabilized cell of Schizosaccharomyces pombe. AB - We reconstituted a protein translocation-transport system composed of permeabilized spheroplasts (P-cells) of the fission yeast Schizosaccharomyces pombe and the precursor of alpha sex pheromone, prepro-alpha-factor of the budding yeast Saccharomyces cerevisiae. We found that P-cells prepared from the spheroplasts formed in 0.7M KCl as an osmotic stabilizer had the activity to transport pro-alpha-factor to the Golgi apparatus. Electron microscopic observations showed that membranes were preserved more intact in the P-cells prepared from the spheroplasts formed in 0.7M KCl than in 0.7M sorbitol. A glycoprotein of S. pombe contains galactose residues, and we detected incorporation of radiolabeled galactose residues into the anti-prepro-alpha factor immunoprecipitable fractions in this S. pombe system, but not in the S. cerevisiae system. This paper reports that a heterologous system of in vitro protein transport was performed, and prepro-alpha-factor has the signals necessary for early steps of the transport in S. pombe. PMID- 1497668 TI - Isolation and sequence determination of cDNA encoding PMP-22 (PAS-II/SR13/Gas-3) of human peripheral myelin. AB - A full length cDNA of PMP-22 (PAS-II/SR13/Gas-3) of peripheral myelin has been isolated from a cDNA library of human fetus spinal cord. The clone is 1823 base pairs (bp) in length and contains a 480 bp open reading frame encoding a polypeptide of 160 residues. The deduced amino acid sequence is highly homologous to PMP-22 from bovine (PAS-II), rat (SR13) and mouse (Gas-3). PMID- 1497670 TI - In vivo targeting of inflamed areas by electroloaded neutrophils. AB - Due to their spontaneous accumulation in inflamed or infected areas, blood phagocytes are potent drug vectors with specific targeting. Drug like molecule loading was obtained by use of cell electropermeabilization in which the impermeability of their plasma membrane is transiently impaired. Electrical conditions were used which allow electroloading of a drug like molecule (propidium iodide) in 70% of leukocytes in a whole blood sample while preserving in vitro functional properties. Slow release of entrapped hydrophilic molecules was observed with a half lifetime longer than 4 hours at 4 degrees C and at 37 degrees C. With an in vivo assay, using a rat model of inflammation, we showed that, as for non-pulsed cells, pulsed neutrophils accumulate 10 times more in an inflamed area than they do in control areas. Phagocyte electropermeabilization is therefore a very efficient way of drug targeting. Accumulation of electropulsed neutrophils in an area of inflammation gives targeted release of the electroloaded drug. PMID- 1497671 TI - Kinetic analysis of duck epsilon-crystallin with L-lactate dehydrogenase activity: determination of kinetic constants and comparison of substrate specificity. AB - A systematic analysis of the kinetic properties of duck lens epsilon-crystallin with lactate dehydrogenase [LDH, (E.C. 1.1.1.27)] activity was carried out by employing some 19 different alpha-keto acids as substrates for this NADH dependent LDH-catalyzed reaction. The steady-state Michaelis and catalytic constants (Km, kcat) were determined for a broad range of organic compounds. The results provide important insights regarding the binding and affinity of substrates to active sites of this enzyme crystallin and indicate a great potential for the application of the stable epsilon-crystallin as a catalyst to the synthesis of some important chiral alpha-hydroxyacids in a convenient and efficient way. It is also demonstrated for the first time that in addition to the enzymatic activity of lactate dehydrogenase, duck epsilon-crystallin also possesses the enzymatic activity of malate dehydrogenase. PMID- 1497672 TI - Homotypic and heterotypic Ca(++)-independent cell adhesion activities of biliary glycoprotein, a member of carcinoembryonic antigen family, expressed on CHO cell surface. AB - Homotypic and heterotypic cell adhesion activities of a carcinoembryonic antigen (CEA) family member, biliary glycoprotein a (BGPa), have been examined. CHO cells transfected with the cDNA for BGPa, CEA, non-specific cross-reacting antigen (NCA) and CGM6 have been used. The BGPa producers showed both homotypic and heterotypic adhesion to CEA and NCA producers. However, they hardly adhered to CGM6 producers. Calcium ion was not required for BGPa-mediated homotypic and heterotypic cell adhesion as well as for the adhesions of other members of CEA family. The results strongly suggested that BGPa may play some important roles through Ca(++)-independent cell adhesion activities. PMID- 1497673 TI - Regulatory role of microsomal 3-hydroxy-3-methylglutaryl-coenzyme A reductase in a tobacco mutant that overproduces sterols. AB - In a tobacco mutant callus, containing up to tenfold more sterols than the wild type genotype, HMG-CoA reductase activity is increased by a factor of approximately three, as is the case in mutant seedlings and plants. The rate of HMG-CoA synthesis from acetyl-CoA by the coupled enzyme system acetoacetyl-CoA thiolase/HMG-CoA synthase, as well as its conversion to acetyl-CoA plus acetoacetate by action of HMG-CoA lyase are not affected. These results confirm the key-regulating role of HMG-CoA reductase in sterol biosynthesis, which seems not to be confined only to the animal kingdom, but can also be extended to plants. PMID- 1497675 TI - Mapping of the dopa decarboxylase gene to the 11A band of the murine genome. AB - A human DOPA decarboxylase (DDC) cDNA probe of 747 base pairs has been used to map the DDC gene by in situ hybridization on mouse metaphase chromosomes. This result indicates that the gene is located on band 11A, near the erythroblastosis oncogene B (erb b) locus. This provides evidence for a synteny group on mouse chromosome 11 and human chromosome 7. PMID- 1497674 TI - A homology domain shared between Drosophila optomotor-blind and mouse Brachyury is involved in DNA binding. AB - The distribution of sequence elements divides the optomotor-blind protein into three regions and is suggestive of a transcriptional regulatory role of this protein. The central region of Omb is homologous to the N-terminal half of the Brachyury protein. The conserved domain of Omb is here shown to possess general DNA binding affinity but has no significant similarity to recognized DNA binding motifs. PMID- 1497676 TI - 13C NMR spectroscopic measurement of glutathione synthesis and antioxidant metabolism in the intact ocular lens. AB - A 13C NMR spectroscopic method for non-invasive, time-resolved measurements of glutathione function in the intact ocular lens maintained in organ culture is described. L-[beta-13C]cysteine (1 mM) included in the incubation medium is incorporated, by way of lenticular amino acid uptake and glutathione biosynthetic mechanisms, into the cysteinyl residue of intralenticular glutathione. 13C-NMR chemical shift measurements facilitate analysis of glutathione synthesis and anti oxidant reactions in the intact tissue. The results of this preliminary study demonstrate the viability of a rapid non-invasive method for monitoring the multiple aspects of glutathione biosynthesis, metabolism, and function in intact tissue. PMID- 1497677 TI - Vitamin E protects nerve cells from amyloid beta protein toxicity. AB - The amyloid beta protein (ABP) is a 40 to 42 amino acid peptide which accumulates in Alzheimer's disease plaques. It has been demonstrated that this peptide and a fragment derived from it are cytotoxic for cultured cortical nerve cells. It is shown here that ABP and an internal fragment encompassing residues 25 to 35 (beta 25-35) are cytotoxic to a clone of PC12 cells at concentrations above 1 x 10(-9)M and to several other cell lines at higher concentrations. Between 10(-9) and 10( 11) M beta 25-35 protects PC12 cells from glutamate toxicity. The antioxidant and free radical scavenger vitamin E inhibits ABP induced cell death. These results have implications regarding the prevention and treatment of Alzheimer's disease. PMID- 1497678 TI - Ceruloplasmin stimulates NADH oxidation of pig liver plasma membrane. AB - NADH oxidation by pig liver plasma membranes is stimulated by ceruloplasmin (CUP) reaching a maximal value at 50 U/ml of CUP. NADH oxidation activated by CUP is proportional to the amount of protein. Concanavalin A (Con A) which recognizes the glucidic residues of the CUP required for binding to the receptor inhibits the NADH oxidation in a dose-responsive manner. Both adriamycin and bathophenantroline disulfonate (BPS), previously reported as transplasma membrane electron transport inhibitors, also inhibit the CUP-stimulated NADH oxidation of pig liver plasma membranes. Our results show a clear interaction between CUP and the NADH oxidase of plasma membrane, which supports an oxidative role for CUP in its growth effect. PMID- 1497679 TI - Footprinting evidence for close contacts of the yeast tRNA(Asp) anticodon region with aspartyl-tRNA synthetase. AB - Chemical footprinting experiments on brewer's yeast tRNA(Asp) complexed to its cognate aspartyl-tRNA synthetase are reported: they demonstrate that bases of the anticodon loop, including the anticodon itself, are in close proximity with the synthetase. Contacts were determined using dimethylsulfate as the probe for testing reactivity of guanine and cytosine residues in free and complexed tRNA. Results correlate with the decrease in aspartylation activity of yeast tRNA(Asp) molecules mutated at these contact positions and will be compared with other structural data arising from solution and crystallographic studies on the aspartic acid complex. PMID- 1497680 TI - Phorbol ester-mediated suppression of cytochrome P450 Cyp1a-1 induction in murine skin: involvement of protein kinase C. AB - Epidermal 7-ethoxyresorufin O-deethylase (EROD) activity was elevated greater than 100-fold within 4 to 7 h of topical treatment of SENCAR mice with 100 nmol dibenz[a,c]anthracene (DB[a,c]A). Treatment of skin with 2 micrograms of 12-O tetradecanoylphorbol-13-acetate (TPA) 2 to 8 h prior to DB[a,c]A application suppressed induction by 80%. Suppression was dose-dependent over the range of 0.01 to 5 micrograms TPA (ID50 approximately 0.6 nmol). EROD activities in normal and TPA-treated epidermis paralleled steady state P450 CYP1A1 mRNA content. Analogs of TPA incapable of activating or down-regulating protein kinase C (PKC) did not suppress induction. Pretreatment of skin with sn-1,2-didecanoylglycerol, an activator of PKC which causes translocation but no down-regulation, did not suppress EROD induction. However, induction was suppressed by chrysarobin, an anthralin analog that causes PKC down-regulation in the absence of prior activation. These studies suggest that PKC participates in the processes associated with Cyp1a-1 induction and that TPA effects Cyp1a-1 induction through its down-regulation of PKC. PMID- 1497681 TI - Antisera to calreticulin inhibits sperm motility in mice. AB - Mouse sperm were rapidly immobilized when exposed to rabbit antisera against rat calreticulin. The inhibition of sperm motility was concentration dependent at dilutions 1:50-350. The velocity of sperm did not change significantly as long as they were motile. Neither motility nor velocity of sperm was affected by adding sheep antisera to bovine calmodulin. The antisera to calreticulin also inhibited in vitro fertilization of mouse eggs. Using the avidin-biotin-peroxidase complex method, the antigen was found to be localized in the acrosome of sperm. The results indicate that calreticulin is present in the acrosome of mouse sperm and may play an important role in sperm motility. PMID- 1497682 TI - Relaxin increases rat heart rate by a direct action on the cardiac atrium. AB - Relaxin (Rlx) is best understood as a protein hormone of pregnancy that can influence pelvic and cervical connective tissue as well as uterine smooth muscle activity. Thus, it was unexpected that dense Rlx binding sites would be found in the rat cardiac atrium. To functionally characterize this finding, isolated rat atria were challenged with Rlx (0.3 to 30 ng/ml), and they responded with an increased rate (+36%) and force (+38%) of contraction Further studies in conscious normotensive and spontaneously hypertensive rats established by minipump circulating Rlx levels of about 0.5 and 5 ng/ml over 1 to 2 wks. There were significant increases in heart rate of 10-15%, with no consistent changes in blood or urine volume, water or food intake, and mean arterial pressure. We conclude that Rlx can directly stimulate rat cardiac atrial activity in vitro and cause chronotropy in vivo. PMID- 1497683 TI - Synthesis and pharmacological evaluation of some phenothiazines as antidepressants. AB - 10-Hydrazino acetyl phenothiazine (II) has been converted to N-10-acetyl amino phenothiazine-N-phenyl thiourea (III) which have been converted to 3-aryl-1-(10 phenothiazine acetyl amino)-2,3-dihydro-2-thioxo-4,6-(1H,5H) pyrimidinones (IV) on condensation with aryl amines and aryl aldehydes yielded 3-aryl-1-(10 Phenothiazine acetyl amino)-5-(substituted phenyl amino methyl)-2,3-dihydro-2 thioxo-4,6-(1H, 5H) pyrimidinediones (Va-k) and 3-aryl-1-(10-phenothiazine acetyl amino)-5-(substituted phenylidine)-2,3-dihydro-2-thioxo-4,6-(1H, 5H) pyrimidinediones (vl-o). The compounds were screened for their antidepressant activity against a tricyclic antidepressant (imipramine). Compounds Va, Vf, Vm and Vi exhibited activity better than imipramine with no toxicity (ALD50 greater than 1000 mg/kg) but Vi showed some side effects. PMID- 1497684 TI - Effect of vinpocetine on red blood cell deformability in vivo measured by a new centrifugation method. AB - A simple new apparatus has been devised to measure red blood cell deformability and the effect of vinpocetine (CAS 42971-09-5) on this property was examined in vivo. The filterability index obtained by this new method correlated well with that obtained by Swank's screen filtration pressure apparatus. Vinpocetine, given as a single oral dose of 10 mg, increased the red blood cell deformability of 5 healthy male volunteers as determined by both methods. The new centrifugation method is simple and suitable for clinical application. Vinpocetine appears to offer a new treatment of cerebral circulatory disorders. PMID- 1497685 TI - Steady state concentrations and diurnal fluctuations of carbamazepine in patients after different slow release formulations. AB - The bioavailability and serum level fluctuations of three carbamazepine (CBZ, CAS 298-46-4) slow release preparations marketed in Germany were compared in patients with epilepsy. Ten patients who were on CBZ monotherapy and had reached a steady state with morning trough levels above 10 micrograms/ml received all 3 preparations in sequential 3-day periods. On the 3rd day of each period, a 24-h serum drug level profile was determined. Only minimal differences could be found. One preparation had a significantly higher AUC than one of the others (p less than 0.05), and this difference seemed to be correlated with higher fluctuations of serum levels and, especially, an increased Cmax. Although the group differences are minimal, more important differences could be observed individually. One patient had, with one of the three preparations, a reduction in seizure frequency but simultaneously developed important signs and symptoms of toxicity. It is concluded that all 3 preparations are equally suitable for chronic antiepileptic drug treatment. In a well-controlled patient, however, interchange between preparations is not advisable as their kinetics in individual patients can be sufficiently different to cause toxicity or seizure relapse. PMID- 1497686 TI - Negative inotropic effects of the new class I antiarrhythmic agents berlafenone and alprafenone on electrically stimulated isolated cardiomyocytes. AB - Isolated cardiac myocytes from adult rats were used in a stimulation chamber to investigate the negative inotropic effects of propafenone and the new compounds berlafenone (1-2'-biphenyloxy)-3-tert-butylamino-propanol-2-hydrochloride, GK 23 G; CAS 18965-97-4) and alprafenone (1-(4-methylphenyl)-3-[3'-(2-hydroxy-3-tert pentylaminopropoxy)-4'- methoxyphenyl]-1-propanonhydrochloride, AH 141; CAS 124316-02-5). This chamber is part of a new device that allows the simultaneous evaluation of mechanics and of the energetics of electrically induced contractions of the myocytes. 1. The contractile behaviour of attaches myocytes was analysed by an image processing system using digitized frames of a CCD camera. 2. The metabolic demand for excitation-contraction coupling was calculated from the drop in oxygen tension (registered by a Clark electrode) caused by suspended myocytes when stimulated in the presence of the contraction inhibiting agent 2,3-butanedione monoxime in the stimulation chamber. 3. The apparent refractory period was evaluated by pacing the myocytes with increasing stimulation rates and determining the frequency at which failure of single contractions occurred. All 3 agents produced a reduction in contraction amplitude of the electrically stimulated myocytes with a similar dose-response relationship (IC50 approx. 10 mumol/l). 4 mumol/l berlafenone reduced the contraction amplitude to 62% of control. Under these conditions the energy expenditure of the contracting cells for excitation and excitation-contraction coupling (ion cycling) was also reduced (77 +/- 17% of control). Since most of this energy is used for Ca2+ (greater than 80%) it may be concluded that a reduced Ca2+ release causes the negative inotropic action of berlafenone.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1497687 TI - Effect of magnesium pyridoxal 5-phosphate glutamate on the hamster cardiomyopathy. AB - 30-day-old polymyopathic hamsters (strain BIO 82.62) were orally treated with either magnesium pyridoxal 5-phosphate glutamate 100 mg/kg, equimolar amounts of magnesium alone (MgCl2 55 mg/kg), or water b.i.d. for 30 days, or sacrificed before treatment. 60-day-old healthy hamsters (strain CLAC) served as controls. Magnesium pyridoxal 5-phosphate glutamate lowered the myocardial calcium content (42.8 +/- 13.1 mmol/kg dry weight) as compared to MgCl2 (70.3 +/- 11.9 mmol/kg dry weight) and water (72.7 +/- 13.6 mmol/kg dry weight). The serum and tissue lipid pattern did not differ between BIO 82.62 and normal hamsters except high serum cholesterol and triglyceride levels in 30-day-old BIO 82.62 hamsters. Myocardial necroses were influenced by neither magnesium pyridoxal 5-phosphate glutamate nor MgCl2. Cytochemical investigation of the ultrastructural calcium localization in the aorta revealed less calcium precipitates with magenesium pyridoxal 5-phosphate glutamate in media myocytes. It is concluded that magnesium pyridoxal 5-phosphate glutamate exerts a calcium antagonistic effect in the cardiomyopathy of the Syrian hamster which is related neither to the magnesium content of magnesium pyridoxal 5-phosphate glutamate nor to its lipid lowering activity. PMID- 1497688 TI - [Absolute bioavailability of beta-acetyldigoxin from tablets and drops in healthy subjects]. AB - In a crossover design in random order 12 healthy male volunteers were given either beta-acetyldigoxin (Novodigal, CAS 5511-98-8) tablets, oral solution or i.v. application at a digoxin equivalent dose of 0.284 mg. To reach steady state each preparation was given for 10 days on a once-daily schedule. On days 8, 9 and 10 of each observation period blood was sampled to determine trough concentrations of digoxin in steady state. In addition, on day 10 blood was collected repeatedly at appropriate time intervals and urine was sampled concomitantly for 24 h. Trough values during steady state and 24 h AUC were used to calculate digoxin bioavailability for tablets and oral solution. From trough values, the mean bioavailability for beta-acetyldigoxin tablets was 91.2% (range 73.1-118.1) and for solution 93.8% (range 65.7-114.8). Using the AUCs 0-24 h at steady state bioavailability was calculated 77.7% for the tablets and 84.5% for the solution. Since trough values in steady state represent the body burden of digoxin which is supposed responsible for the therapeutic effect, trough values should be given priority for the determination of digoxin bioavailability from beta-acetyldigoxin tablets and solution. All formulations were well tolerated. No clinically relevant side effects were observed. PMID- 1497689 TI - Influence of isosorbide-5-mononitrate on the circadian rhythm of angina pectoris. AB - Efficacy and safety of two different dose regimens of isosorbide-5-mononitrate (isosorbide mononitrate, ISMN, Mono Mack, CAS 16051-77-7) (40 mg ISMN in the morning, n = 187 vs. 20 mg ISMN b.i.d. morning and early afternoon, n = 195) were evaluated in an open, randomised study in patients with symptomatic myocardial ischemia. Circadian rate, frequency, severity and duration of angina pectoris attacks, as well as the additional need of short-acting nitrates were assessed on 3 consecutive days before and at the end of the first and second weeks of treatment, respectively. In both treatment groups, a statistically significant decrease of frequency and severity of angina pectoris attacks was observed as compared to baseline. Apart from minor variations, no statistically significant differences were found between the two treatment groups. PMID- 1497691 TI - Synthesis and inhibitory effects of 1,2,4-triazole derivatives on platelet aggregation. AB - Various derivatives of triazole substituted in the 2-position were prepared, and their activity on platelet aggregation tested. Compounds 4 and 14 had the most powerful action. These agents were thought to inhibit platelet aggregation via an inhibition of the cyclo-oxygenase-peroxidase complex (PGS complex), preventing synthesis of prostaglandins. PMID- 1497690 TI - [Metabolic consequences of long-term antihypertensive treatment with co dergocrine mesylate/nifedipine in high age groups]. AB - Possible metabolic changes during chronic treatment is of specific importance for the development of antihypertensive drugs. The impact of a combination treatment with co-dergocrine mesilate/nifedipine (Pontuc; CAS 8067-24-1 resp. CAS 21829-25 4) on the lipid metabolism as well as hematological and biochemical values was evaluated in a group of hypertensive patients. HDL-cholesterol remained unchanged, whereas total cholesterol and LDL-cholesterol slightly decreased, apoprotein AI increased and apoprotein B decreased. In conclusion the results of this study indicate that co-dergocrine mesilate/nifedipine has no negative impact on the lipid metabolism in patients with essential hypertension. PMID- 1497692 TI - Effect of anethole dithiolthione on human platelet aggregation. AB - Anethole dithiolthione (ADT) (10 mumol/l) inhibited platelet aggregation and the formation of thromboxane (Tx)B2 in plasma in response to adenosine diphosphate (ADP), epinephrine and arachidonic acid (AA). ADT partially inhibited platelet aggregation and TxB2 formation in plasma induced by thrombin, phorbol myristate acetate and calcium ionophore A23187 and increased the lag time of collagen induced aggregation at concentrations in the range 10-40 mumol/l. ADT (100 mumol/l) completely inhibited the aggregation of washed platelets challenged with thrombin. ADT had no additive effect on the inhibition of thrombin-induced platelet aggregation by acetylsalicylic acid. ADT was a more effective inhibitor of AA-induced platelet aggregation than butylated hydroxytoluene. ADT inhibited the release of 3H-AA from platelet phospholipids in response to ADP and collagen. It is suggested that ADT inhibits platelet aggregation by inhibiting thromboxane synthesis and preventing AA release. PMID- 1497694 TI - [Binding affinity of ibuprofen in human tissues]. AB - In vitro binding of ibuprofen (CAS 15687-27-1) to various human tissues was studied to explain differences in tissue concentration after local application of ibuprofen cream. Radioactive ibuprofen, was incubated with human skin, subcutaneous tissue, muscle, tendon, joint capsule for 2 h at 37 degrees C. Tissue specimens were washed and radioactivity was measured by a liquid scintillation counter. The results show specific binding of ibuprofen to the various tissues of different degrees. Despite of interindividual differences muscle tissues showed the highest, tendons the lowest concentrations of ibuprofen. These findings may explain the in vivo results, where higher concentrations of ibuprofen were found in muscle tissue compared with subcutaneous tissue. PMID- 1497693 TI - Effects of the anti-platelet agent cilostazol on peripheral vascular disease in patients with diabetes mellitus. AB - Effects of cilostazol (OPC-13013, CAS 73963-72-1), a selective inhibitor of platelet cAMP-phosphodiesterase, on peripheral vascular disease in diabetes mellitus were studied. Cilostazol in a dose of 200 to 300 mg/d was administered to 5 diabetic patients with arteriosclerosis obliterans. Skin temperature of the finger and the toe, which reflects blood flow to the tissue, was selected as an objective index of cilostazol effects and measured by infra-red thermography at a constant temperature of 26 degrees C. Before administration, digital skin temperatures were low in 9 limbs of 5 patients. 200 mg/d of cilostazol significantly (p less than 0.001) increased the digital skin temperatures of 8 limbs, the increase (mean +/- SD) ranging from 29.9 +/- 1.4 degrees C to 33.2 degrees C +/- 1.2 degrees C for the average skin temperatures and from 28.7 +/- 2.1 degrees C to 33.1 +/- 1.5 degrees C for the lowest ones. An increase in the dose to 300 mg/d resulted in further elevation of skin temperatures of the digits. Cilostazol constantly elicited an increase in blood flow to the digits within the range of its therapeutic dose. This effect was observed about 1 month after initiation of administration and persisted while administration was continued. The measurement of digital skin temperatures by infrared thermography provided a noninvasive means to individualize the dosage of cilostazol and to monitor the cilostazol effect and patient complicance during long-term administration. It is concluded that cilostazol exerts a potent and steady vasodilatory effect on peripheral circulation in patients with diabetes mellitus. PMID- 1497695 TI - Study of the anti-inflammatory activity of Populus tremula, Solidago virgaurea and Fraxinus excelsior. AB - Aqueous/alcoholic extracts of Populus tremula, Solidago virgaurea and Fraxinus excelsior (components of Phytodolor N) were tested individually and in 3 different combinations for anti-inflammatory activity using carrageenan induced edema and/or adjuvant induced arthritis of the rat paw. The tested combinations as well as the individual extracts significantly reduced the paw edema to varying degrees and also dose dependently inhibited the arthritic paw volume. The anti inflammatory activity of the combinations was respectively comparable to the tested doses of diclofenac. PMID- 1497696 TI - Effect of polyunsaturated phosphatidylcholine on liver regeneration onset after hepatectomy in the rat. AB - The purpose of this study was to examine the effect of polyunsaturated phosphatidylcholine (PPC, Essentiale) on the onset of liver regeneration after partial hepatectomy (PH). Hepatectomy was carried out on rats, and immediately after operation doses of 25, 50 or 250 mg PPC/kg b.w. were injected into the vena femoralis. The control group consisted of saline-injected PH rats. The rats were killed 18, 21, 24 and 30 h after PH. The course of liver regeneration was assessed by measuring the incorporation of labelled thymidine into DNA and the hepatocyte mitotic activity. After PPC injection no values of liver DNA specific activity differing from baseline were observed. However, higher values of hepatocyte mitotic activity and lower liver triglyceride levels were found as compared to the saline-treated rats. These observations indicate that the administration of PPC has a favourable effect on liver regeneration after PH. PMID- 1497697 TI - Therapeutic efficacy of latoconazole in formulations of clinical use on experimental dermatophytosis in guinea pigs. AB - Therapeutic efficacy of clinical dosage forms of latoconazole (NND-318, CAS 101530-10-3), related compound of ketene dithioacetals with an imidazole ring, was examined on two experimental tinea models: a recently developed tinea pedis model and a conventional tinea corporis model in guinea pigs. The efficacy of the dosage forms was estimated on the basis of the rate of fungus-positive skin cultures and/or the score of skin lesions, and was compared to the other antifungal agents, bifonazole, clotrimazole and tolnaftate. While these reference agents exhibited curative effect on the tinea corporis model, the tinea pedis model was considerably resistant to the therapeutic treatment of the agents. The cream preparation and solution of lactoconazole at concentrations of more than 0.25% were highly effective in either tinea models, and at concentrations of more than 1%, lactoconazole achieved complete mycological cure. These results suggest that 1% of lactonazole is an optimal concentration for clinical use. PMID- 1497698 TI - Fraction of absorbed drug at the time of peak plasma concentration in an open one compartment model after simultaneous oral and intravenous administration. AB - When a drug is simultaneously given orally and intravenously, the plasma concentration generally reaches a maximum. The purpose of this paper is to assess the extent of absorbed drug at the time Tmax. PMID- 1497699 TI - Thrombolytic properties in a rabbit jugular vein thrombosis model of a tissue type plasminogen activator mutant lacking the growth factor--and kringle one domains. AB - In a rabbit jugular vein thrombosis model, the thrombolytic properties of melanoma tissue-type plasminogen activator (mt-PA), recombinant t-PA (rt-PA), and a t-PA mutant that lacked the growth factor- and kringle one-domain (designated FK2P, as it contained the finger-, kringle two-, and protease-domain) were compared. Over the dose range tested (3.75 to 30 nmol/kg) a similar, dose dependent, thrombolytic efficacy was found for the 3 enzymes when given as bolus injections. When given as a 90-min infusion, FK2P was superior to rt-PA at the tested dose of 15 nmol/kg. The effects on systemic plasma fibrinogen, plasminogen and alpha 2-antiplasmin consumption were much larger for rt-PA and FK2P than for mt-PA. The analogue FK2P was cleared more slowly than mt-PA or rt-PA, despite a similar initial alpha half-life: the mean residence time of FK2P was about 10 times as large as that of mt-PA or rt-PA. A comparison with data obtained in vitro suggested that in vivo thrombolytic performance cannot easily be predicted from in vitro data. The efficacy of a thrombolytic agent will also depend on its clearance rate, and may also, within a chosen model, depend on the way it is administered. PMID- 1497700 TI - Reporting negative studies in the mass media. PMID- 1497701 TI - Medical education: capitalizing on the lecture method. PMID- 1497702 TI - Physicians and pharmaceutical companies. PMID- 1497703 TI - Response of newly hatched chicks to inanition. AB - Newly hatched chicks were kept for up to 48 hours without food and water and compared with a control group of chicks given access to food and water within six hours of hatching. The deprived chicks progressively lost body water and developed increases in plasma total protein concentration consistent with a decrease in plasma volume. They demonstrated a stronger motivation to drink and drank more when offered water, suggesting that they had become dehydrated. There was evidence, however, that normally access to food was necessary to initiate drinking. The deprived chicks continued to rely on fat metabolism to supply their energy needs whereas the fed birds showed rapid reductions in circulating levels of beta-hydroxybutyrate and increases in plasma glucose and liver glycogen concentrations, indicating a change to carbohydrate-orientated energy metabolism. The deprived chicks lost weight at an average of 0.14 g/hour and weighed 16.5 g less than the fed chicks after 48 hours. PMID- 1497704 TI - Inhibitors of human neutrophil cathepsin G: structural and biochemical studies. AB - The interaction of a series of sulfonate and phosphate esters derived from N hydroxysuccinimide with human leukocyte cathepsin G was investigated. The synthesized compounds were found to be time-dependent inhibitors of the enzyme. The composite interplay of steric and electronic effects leads to the formation of acyl enzymes of variable stability, ultimately resulting in partial or full recovery of enzymatic activity. Compounds acting via phosphorylation of the active site serine inactivated the enzyme rapidly and irreversibly. PMID- 1497705 TI - Health risks associated with bathing in sea water. PMID- 1497706 TI - Medical abortion. PMID- 1497707 TI - The Hillsborough tragedy. PMID- 1497708 TI - Best interests and clinical decisions. PMID- 1497709 TI - I disagree... PMID- 1497710 TI - The angle osteotomy: elevating it to a science. PMID- 1497711 TI - Response to "Prescription privileges: psychology's next frontier?" or the siren call: should psychologists medicate? PMID- 1497712 TI - Aminoglycoside toxicity. PMID- 1497713 TI - Suicidal ideation as a presenting complaint. PMID- 1497714 TI - Supplementary oxygen causing surgical emphysema. PMID- 1497715 TI - Cost implications of alternative treatments for AIDS patients with cryptococcal meningitis. PMID- 1497716 TI - Oesophageal cancer in Britain. PMID- 1497717 TI - Steroid therapy in quiet nerve paralysis. PMID- 1497718 TI - Symptom responses of female Vietnam veterans to Operation Desert Storm. AB - OBJECTIVE: This study examined the status of symptoms of posttraumatic stress disorder (PTSD) in a cohort of women after the onset of Operation Desert Storm. METHOD: Seventy-six non-treatment-seeking Vietnam veterans were obtained from lists of those who recently had participated in other research projects conducted at the National Center for Post-Traumatic Stress Disorder. Before the onset of Operation Desert Storm, subjects had completed a set of psychometrically valid instruments measuring general psychological symptoms and PTSD symptoms (e.g., SCL 90-R, Mississippi Scale for Combat-Related Posttraumatic Stress Disorder). On the basis of the latter scale, subjects were divided into groups with and without PTSD symptoms. At the height of the military conflict, subjects were recontacted and asked to complete the SCL-90-R and the Veterans Update Form, a measure assessing changes in PTSD symptoms. RESULTS: Multivariate analyses indicated that while most female Vietnam veterans experienced some intensification of stress related symptoms during Operation Desert Storm, those who had previously reported high levels of PTSD were significantly more susceptible to greater distress. CONCLUSIONS: Results of this survey indicate that female Vietnam veterans with prior wartime exposure are an at-risk population for the intensification of stress symptoms after the recurrence of a military conflict. PMID- 1497719 TI - Improving preregistration training. PMID- 1497720 TI - Improving preregistration training. PMID- 1497721 TI - Re: Lord's procedure--the best operation for hydrocele? W. Albrecht et al. Br. J. Urol., 68, 187-189, 1991. PMID- 1497722 TI - Declining trends in some STDs in Belgium. PMID- 1497723 TI - Nonhealing leg ulcers: a manifestation of basal cell carcinoma. PMID- 1497724 TI - Nonhealing leg ulcers. PMID- 1497725 TI - Reconstruction of internal orbital fractures with Vitallium mesh. PMID- 1497726 TI - Article on HIV in Cuba criticized. PMID- 1497727 TI - Longevity of jazz musicians: Spencer replies to Haaga and Rothman. PMID- 1497728 TI - Interpreting CAGE scores. PMID- 1497729 TI - Beta-lactam antibiotics and vitamin K. PMID- 1497730 TI - Playing God--revisited. PMID- 1497731 TI - Gastroduodenal perforation in preterm babies treated with dexamethasone for bronchopulmonary dysplasia. PMID- 1497732 TI - Air bag deployment and injury reduction. PMID- 1497733 TI - Quality of life on in-center hemodialysis versus CAPD. PMID- 1497734 TI - C4BQ0 as a marker of genetic predisposition to liver cirrhosis. PMID- 1497735 TI - Olfactory neuroblastoma. PMID- 1497736 TI - Certified nurse midwives. PMID- 1497737 TI - Delayed diagnosis of gonococcal arthritis of the foot caused by beta-lactamase producing Neisseria gonorrhoeae. PMID- 1497738 TI - Contact neodymium:YAG laser for cyclophotocoagulation. PMID- 1497739 TI - Lumbar neural foramen remodeling by disk herniations. PMID- 1497740 TI - Ion chromatographic measurement of fluoride and sulfur dioxide in samples collected at aluminum smelters. PMID- 1497741 TI - Nocturnal temperature in LLPDD. PMID- 1497742 TI - New possible indications of pimozide. PMID- 1497743 TI - 230-kD and 180-kD bullous pemphigoid antigens are distinct gene products. PMID- 1497744 TI - Re: Spontaneous recovery of renal function after resection of contralateral hypernephroma. PMID- 1497745 TI - An unusual case of renal failure after pregnancy. PMID- 1497746 TI - Magnesium sulfate is an unfit anticonvulsant in eclampsia. PMID- 1497747 TI - Platelet dysfunction and neurovascular surgery. PMID- 1497748 TI - Awareness under anaesthesia. PMID- 1497749 TI - Issues concerning the sedation of children for radiation therapy. AB - Radiation therapy is a commonly used modality to treat certain pediatric malignancies. To optimally treat a child's tumor while sparing normal, developing tissues from both short- and long-term side effects, the child must be in a fixed and reproducible position on the treatment table. Many children, especially those under age three, very anxious children, and those who are developmentally disabled, may require daily sedation for a course of radiotherapy. Issues concerning the use of sedation, types of drugs used, and the nurse's role in the sedation process are presented in this article. PMID- 1497750 TI - Genomic 3' terminal sequence comparison of three isolates of rabbit haemorrhagic disease virus. AB - Comparison of sequence data is necessary in older to investigate virus origins, identify features common to virulent strains, and characterize genomic organization within virus families. A virulent caliciviral disease of rabbits recently emerged in China. We have sequenced 1100 bases from the 3' ends of two independent European isolates of this virus, and compared these with previously determined calicivirus sequences. Rabbit caliciviruses were closely related, despite the different countries in which isolation was made. This supports the rapid spread of a new virus across Europe. The capsid protein sequences of these rabbit viruses differ markedly from those determined for feline calicivirus, but a hypothetical 3' open reading frame is relatively well conserved between the caliciviruses of these two different hosts and argues for a functional role. PMID- 1497751 TI - [Alarming rate of absenteeism due to illness]. PMID- 1497752 TI - Assessment of nutrition care provided to patients with diabetes in primary-care clinics. PMID- 1497753 TI - Geostatistical and morphological methods applied to three-dimensional microscopy. AB - Three-dimensional (3-D) images of osteocyte lacunae were examined on a confocal microscope. Both geostatistical and morphological processing techniques were used to improve and to analyse them. By a geostastical approach, this study aims at improving 3-D confocal images before any further image processing. Optimized linear filters, which take account of the second-order statistics and the 3-D structure of the data, allow for the removal of imperfections such as noise and/or blur due to the axial convolution, and interpolate voxels on a face centred cubic grid from an initial cubic grid. An application of this technique to 3-D biological images is demonstrated. In a second step, a 3-D binary image is digitized and cleaned with 3-D morphological filters. The standard 3-D measurements cannot be applied in this case, since all osteocytes cut the border of the field. For this reason a 3-D Boolean model has been adjusted, from which it is possible to derive all useful information on the repartition and the morphology of the osteocytes. PMID- 1497754 TI - The involucrin gene of Old-World monkeys and other higher primates: synapomorphies and parallelisms resulting from the same gene-altering mechanism. PMID- 1497755 TI - Surface-bound optical probes monitor protein translocation and surface potential changes during the bacteriorhodopsin photocycle. AB - Light-induced H+ release and reuptake as well as surface potential changes inherent in the bacterio-rhodopsin reaction cycle were measured between 10 degrees C and 50 degrees C. Signals of optical pH indicators covalently bound to Lys-129 at the extracellular surface of bacteriorhodopsin were compared with absorbance changes of probes residing in the aqueous bulk phase. Only surface bound indicators monitor the kinetics of H+ ejection from bacteriorhodopsin and allow the correlation of the photocycle with the pumping cycle. During the L550-- -M412 transition the H+ appears at the extracellular surface of bacteriorhodopsin. Surface potential changes detected by bound fluorescein or by the potentiometric probe 4-[2-(di-n-butylamino)-6-naphthyl]vinyl-1-(3 sulfopropyl)pyridinium betaine (di-4-ANEPPS) occur in milliseconds concomitantly with the formation and decay of the N intermediate. pH indicators residing in the aqueous bulk phase reflect the transfer of H+ from the membrane surface into the bulk but do not probe the early events of H+ pumping. The observed retardation of H+ at the membrane surface for several hundred microseconds is of relevance for energy conversion of biological membranes powered by electrochemical H+ gradients. PMID- 1497756 TI - The 'new' curriculum: is it new? PMID- 1497757 TI - Use of computers among occupational health nurses: results of a survey. AB - 1. A survey of occupational health nurses revealed that they are using computers at work for a variety of activities, and find computers to be useful tools in their jobs. 2. Occupational health nurses who use computers at work differ from nonusers in level of education, experience, and salary. 3. Nurses who do not use computers at work are interested in learning more about computers, and are willing to and interested in attending seminars to gain additional knowledge in this area. PMID- 1497759 TI - Understanding corporate cultures: use of systems theory and situational analysis. AB - 1. A company's culture is its heroes, values, myths, and symbols. In strong cultures, the lives and productivity of employees are shaped by where they work. 2. Understanding corporate cultures, generally, and the one in which one works, specifically, can help the occupational health nurse develop and implement intervention strategies specific to that company's culture. 3. A strong culture has a system of rules dictating employee behavior. In a less strong culture, the rules and definitions are less rigid, facilitating more flexibility and less predictability. PMID- 1497758 TI - National Asthma Education Program Expert Panel report: guidelines for the diagnosis and management of asthma. AB - 1. Asthma, a chronic lung disease that affects 10 million Americans, is receiving increased attention as a public health problem due to increased occurrence and number of reported deaths. 2. This article presents an overview of the National Asthma Education Program Expert Panel guidelines, specifically addressing the definition and pathophysiology of asthma, effective management and control of asthma, and special considerations in asthma management. 3. Implications of the Expert Panel guidelines for occupational health nurses are addressed. PMID- 1497760 TI - Program descriptions: a positive outcome from change. AB - 1. Major organizational restructuring was the impetus for standardization of occupational health practice at three hospital sites. 2. A generic framework was devised to describe the key occupational health programs. 3. The process of developing these program descriptions yielded obvious quality assurance monitors. 4. Corporate change often is perceived as threatening. The development of a useful tool through cooperative team effort has produced a positive outcome. PMID- 1497761 TI - Resource information on fetal protection in the workplace. PMID- 1497762 TI - Environmental hazards in the workplace: legal and safety considerations. AB - Both the employer and the employee must work together to provide the best possible work environment. The occupational health nurse can facilitate the interaction and communication between these groups to protect the employer and the employee. The company must follow legal guidelines related to hazardous materials, and the employees must understand and adhere to the established policies and procedures developed for their safety. The nurse can help assure that each is protected. PMID- 1497763 TI - [Piriform sinus fistulas as rare hypopharyngeal abnormalities, diagnosis and therapy]. AB - We report on the history, clinical findings, diagnostic examinations and the therapy of three patients with a left piriform sinus fistula, probably a fourth pharyngeal pouch. Our patients show recurrent inflammation and abscesses of the left lateral neck. X-ray (gastrografin swallow) showed the fistula originating from the floor of the left piriform sinus. CT-scan was helpful in the previously operated area, although the fistula could be shown by ultrasonic examination. Recurrent abscesses of the lateral neck may be caused by sinus piriform fistula. It is important to search for this rare malformation of the lateral neck. PMID- 1497764 TI - [Necrosis of the tongue in temporal arteritis. Case report]. AB - Because of the rich blood supply ischemic necrosis of the tongue is extremely rare. But if it happens though, the reason is most often due to temporal arteritis. It predominantly occurs in elderly women, like in our case. The correct diagnosis should be established as soon as possible because high-dose cortisone therapy both relieves the patient's complaints and prevents life threatening complications. PMID- 1497765 TI - [Ossification of the stapedius tendon as a rare cause of conductive hearing loss]. AB - Ossification of the stapedial tendon is a very rare cause of conductive hearing loss. In addition to a review of the literature, two further cases of unilateral hearing impairment are reported. In both cases, division of the ossified tendon led to a complete disappearance of the middle-ear problem. Apart from middle ear malformations, infections of the middle ear may also give rise to ossification of the stapedial tendon. PMID- 1497766 TI - [Holmium:YAG infrared laser and UV-Excimer. Laser effects on oral mucosa]. AB - The in-vivo tissue ablation characteristics of a pulsed infrared laser (Holmium:YAG, lambda = 1980) and a pulsed excimer laser (XeCl, lambda = 308 nm) were studied. The holmium laser energy was coupled into nylon fibres. The excimer laser energy was coupled into quartz fibers. Laser incisions were made on white rats at different sites of the tongue. Power settings of 400 mJ per 2.5 microseconds pulse at 5 pulses per second for the holmium:YAG laser and 250 mJ per 1 microsecond pulse at 20 pulses per second for the excimer laser were used. Thermal gradients following laser application were measured. Excellent control of depth of tissue ablation was noted for both types of lasers. The tissue response was examined by light microscopy. Histological studies revealed tissue defects with clean contours. The coagulative necrosis zone for the 400 mJ holmium:YAG injuries measured from 370 microns to 640 microns, compared with 40 microns to 160 microns with the 250 mJ UV-excimer injuries. Wound healing was studied over a six-week period. Histologically, wound closure was completed after four weeks showing re-epithelialization without scar formation for both types of laser. The in-vivo tissue ablation characteristics and the operation reliability of the two lasers were compared. PMID- 1497767 TI - [Immunologic behavior of human tracheal transplants]. AB - In this study we tried to investigate the antigenicity of human tracheal allografts. We found transplantation antigens in the mucosa and the mixed glands using monoclonal antibodies in an indirect immunoperoxidase method. However these antigens were able to be destroyed with a chemical preservation procedure. The diminution of the antigenicity could be also achieved in a tracheal transplant human recipient. These results show that the preserved trachea may be immunologically a suitable material for reconstruction in surgery of the trachea. PMID- 1497768 TI - [Interposition connectors with heparin coating for vascular anastomosis of microsurgical tissue flaps]. AB - The intraluminal surface of interposition connectos which are introduced for the quick vascular connection of microsurgical free flaps was coated by heparin. This heparin coating proved to be stable at the polyurethane wall until the intraluminal surface of the interposition connectors with a length of 15 mm was coated by a layer of endothelial cells. 90% of the experimental venous connections didn't show a thrombus formation and were open for the blood flow 10 days postoperatively. The experimental free flaps which were connected by this way had survived 21 days postoperatively and showed a regular healing. PMID- 1497769 TI - [Medical ENT endoscopic studies in the iron and steel industry]. AB - 461 chromium- and nickel-exposed steelworkers were otolaryngologically examined by endoscopy. Besides chronic inflammatory diseases of the ear, nose and paranasal sinuses, the clinical diagnosis of leukoplakia and hyperplastic laryngitis was made for 30 workers. In no case a lesion suspicious of cancer was found. Office staff showing no such occupational risk factors served as the control group. It was found that in both groups smoking has to be assumed as the decisive factor for the development of chronic inflammation and precancerous changes in the oral cavity and the larynx. PMID- 1497770 TI - [Perioperative single dose prevention with cephalosporins in the ENT area. A prospective randomized study]. AB - Perioperative systemic antibiotic cover is usually recommended in major head and neck surgery with the aim of preventing postoperative wound infection. The surgeon must administer the drug most suitable for the particular operation and patient at an adequate dosage and over an adequate period. On the other hand, he has an obligation to minimize costs and find ways of avoiding the development of bacterial resistance to the antibiotic. This means that prophylactic antibiotics may not have too broad an antibacterial spectrum and may only be used over the short term. In an attempt to improve antibiotic prophylactic in head and neck surgery, we tested the effectiveness of a perioperative single-dose antibiotic cover with cefuroxim (Zinacef) in patients undergoing parotidectomy, sinus surgery or neck dissection with no transcutaneous exploration of the pharynx. This single-shot prophylaxis was compared with a three-shot, 24-hour regimen using the same antibiotic. The two regimens were equally effective in preventing wound infection and no case of infection was observed among the 106 patients involved. Preoperative concentrations of cefuroxim were measured in serum and tissue, and the large majority of specimens showed effective concentrations against the typical wound infection bacteria. In conclusion, a perioperative single-dose administration of cefuroxim proved to be suitable prophylaxis against postoperative wound infection in head and neck surgery. PMID- 1497772 TI - [Povidone-iodine containing gelatin sponge for tamponade in ear surgery]. PMID- 1497771 TI - [Dose-finding study for hyperfractionated, accelerated radiotherapy plus simultaneous carboplatin administration in patients with locoregionally advanced head and neck cancer]. AB - Therapy of large inoperable squamous cell-carcinomas of the head and neck is considerably problemful. Combined simultaneous radio-chemotherapy with carboplatin and radiotherapy with hyperfractionated accelerated radiation is small effective than conventional monofractionated radiotherapy alone and may reduce side effects. Aim of the following study was dosage optimisation of the applicated carboplatin. PMID- 1497773 TI - [Deafness after previous stapes repair]. PMID- 1497774 TI - An objective structured clinical examination for the licentiate: report of the pilot project of the Medical Council of Canada. AB - The Medical Council of Canada (MCC) administers a qualifying examination for the issuance of a license to practice medicine. To date, this examination does not test the clinical skills of history taking, physical examination, and communication. The MCC is implementing an objective structured clinical examination (OSCE) to test these skills in October 1992. A pilot examination was developed to test the feasibility, reliability, and validity of running a multisite, two-form, four-hour, 20-station OSCE for national licensure. In February 1991, 240 volunteer first- and second-year residents were tested at four sites. The candidates were randomly assigned to one of two forms of the test and one of two sites for two of the four sites. Generalizability analysis revealed that the variance due to form was 0.0 and that due to site was .16 compared with a total variance of 280.86. The reliabilities (inter-station) were .56 and .60 for the two forms. Station total-test score correlations, used to measure station validity, were significant for 38 of the 40 stations used (range .14-.60). The results of the OSCE correlated moderately with the MCC qualifying examination; these correlations were .32 and .35 for the two test forms. Content validity was assessed by postexamination questionnaires given to the physician examiners using a scale of 0 (low) to 10 (high). The physicians' mean ratings were: importance of the stations, 8.1 (SD, 1.8); success of the examination in testing core skills, 8.1 (SD, 1.6); and degree of challenge, 7.8 (SD, 2.1). The results indicate that a full-scale national administration of an OSCE for licensure is feasible using the model developed. Aspects of validity have been established and strategies to augment reliability have been developed. PMID- 1497775 TI - A new program to enhance the teaching and assessment of clinical skills in the People's Republic of China. AB - The authors describe the history and current state of development of an ongoing and still-evolving collaboration--between three Chinese medical schools, the China Medical Board of New York, Inc. (CMB), and one of the authors (PLS) and her staff at the University of Massachusetts Medical School--to enhance the teaching and assessment of clinical skills in the schools. The program grew out of a request by the three schools to the CMB for assistance in improving their process of evaluating students. Its goal is to develop a uniform and comprehensive course for teaching and assessing basic clinical skills. Standardized patients are also being used as instructors and evaluators. The program is co-sponsored by the three schools and the CMB. Background is given about the CMB, its involvement in Chinese medical education, and its American perspective on the nature of education in Chinese institutions of modern medicine and the factors that can assist and impede educational change. The authors present the mechanisms of the program, the benefits that have occurred so far, and the problems encountered in creating the model curriculum to teach clinical skills that is now being implemented by the three schools. Future plans are outlined, including the hope that the three schools will serve as a resource and disseminate some or all aspects of the new approach to similar medical schools in China, and that the program can serve as a model for implementation of similar programs in other countries. PMID- 1497776 TI - Storytelling as a method for teaching values and attitudes. AB - Storytelling is not widely accepted as a teaching method in medical education, sometimes for valid reasons that are explained by the authors. Yet clinician teachers who choose and tell stories appropriately--especially if these are stories of their own clinical experiences--can stimulate their students to examine their values and attitudes in ways that would be hard or impossible to achieve by other methods. The present article, which contains a story of the type advocated, shows how storytelling can help students and residents discuss and overcome their crises of professionalization and come to grips with the troubling aspects of the doctor-patient relationship. The authors maintain that storytelling allows educators to bring the discussion of values and attitudes to where students are most likely to appreciate and understand the message--the clinical encounter. PMID- 1497777 TI - A computer-based information access and management system for students. PMID- 1497778 TI - The Negev Project in community-based training and health services: medical education confronts the "tea lady". PMID- 1497779 TI - Fourth-of-July fireworks over national health care. AB - On July 3, President George Bush devoted his annual Fourth-of-July radio message to the American people to the issue of health care reform. What follows are slightly edited transcripts of the president's message and the response of the Democratic Party, which was delivered by Senate Majority Leader George Mitchell (D-Maine) and also broadcast on July 3. PMID- 1497780 TI - A new problem-solving curriculum. PMID- 1497781 TI - A way to assure curricular quality. PMID- 1497782 TI - A mentorship program for minority students. PMID- 1497783 TI - What we say and what we do: self-reported teaching behavior versus performances in written simulations among medical school faculty. AB - Much of the research in medical education is performed through the use of self reporting questionnaires. Although this can be a valid way to conduct research, little effort has been made to examine the fit between what teachers self-report and what they actually do. In an attempt to investigate this, the authors interviewed 47 preclinical faculty members at two large medical schools in 1990. The faculty members were initially given a questionnaire asking them to self report in four categories: interactive skills; knowledge or abilities they considered important for students to develop; factors that influenced their curriculum development; and sources from which they sought pedagogical assistance. This was followed by four written simulations that examined four areas of teaching: small-group discussions, course design, lecturing, and test construction. In addition, the authors specifically sought to identify any differences in teaching philosophy and practice between those preclinical faculty who were physicians and those who were not, as well as any interinstitutional differences. Although in certain instances there was a strong correlation between self-reporting and performance as measured by a simulated teaching scenario, in most instances the correlation was quite low. Consequently, the authors suggest that researchers must be careful in their use of self-reporting as a means of assessing teaching behavior, and that whenever possible, researchers should observe the teachers they are studying. PMID- 1497784 TI - Conceptualizing curriculum for graduate medical education. AB - Several recent developments affecting graduate medical education (GME) have kindled an interest in curriculum. For the most part, however, GME curriculum is being conceived in terms of behavioral learning objectives. The authors find this approach to curriculum ill-suited for the reality and complexity of housestaff training. Several other approaches are considered but none, they conclude, fits well with the mission of GME. Instead, they propose a more comprehensive experiential conception of curriculum for GME. This approach stems from an experiential learning paradigm and a commitment to curriculum as an expression of valued activities rather than of predetermined objectives. Taking as an example a curriculum for an ambulatory care block rotation, the authors show how an experiential curriculum can be developed and how it can be used to frame the residents' rotation, including patient care and didactic program. PMID- 1497785 TI - Using a database to analyze core basic science content in a problem-based curriculum. AB - As medical schools critically reevaluate their methods of instruction and as the number of innovative programs increases, the content delivered across disciplines must be carefully reviewed. However, few methods of content analysis have been applied to problem-based programs. In 1989-90 and 1990-91, the authors analyzed the distribution of basic science content in the 53 cases in the problem-based curriculum of Rush Medical College of Rush University. They developed a content vocabulary and created a database using a widely available computer software program. The content areas specific to each case were identified by faculty using the content vocabulary. To determine whether these content areas were actually identified by the students participating in the problem-solving sessions, the authors surveyed the 36 student participants in the classes of 1993 and 1994 and also interviewed the 15 faculty facilitators of the sessions. The surveys and interviews demonstrated that over 90% of the content areas identified by the faculty were actually covered by the students. The authors conclude that the database assists in their review of the curriculum for omission and redundancy. Other uses and limitations of this method are also discussed. PMID- 1497786 TI - The role of natural science in the premedical curriculum. AB - The authors examined the role of natural sciences in entering students' academic preparation for admission to the University of California, Los Angeles (UCLA), School of Medicine by analyzing the college transcripts of 290 students in the classes of 1990 and 1995 to determine the breadth of the students' college course work. In addition, during 1990 the authors surveyed 126 full-time basic science and clinical faculty about their views regarding the optimal requirements for admission. The vast majority of the students' college courses had been in the natural sciences, with no significant change in this finding over the five-year period. Of the faculty surveyed, 97 (77%) responded, stating that the majority of prerequisites should be in the natural sciences; their prerequisites were similar to UCLA's 1991-92 admission requirements. The authors suggest that the persistently narrow focus on the natural sciences as a preparation for medical school may explain the nationwide need to instruct medical students in the humanities, and that perhaps it is time to require non-science courses to broaden the educational backgrounds of entering students. PMID- 1497788 TI - Use of free time in the third and fourth years of a flexible curriculum. AB - In 1988, the author surveyed senior students on their use of the six months of free time in the junior-senior biennial at the University of Minnesota Medical School-Minneapolis. The students were asked both to provide detailed reports on their free-time activities and to rank the three activities they considered to be most helpful to their professional development. Of 274 seniors, 191 (70%) responded. The students had used a majority of their free time for pursuits related to education and advancement of their careers. Approximately one-third of the time had been used for vacations. The activities the students viewed as most helpful included research, interviewing for residency positions, vacation, study elsewhere, and preparation for the National Board of Medical Examiners Part II examination. The author suggests that when free time is made available in a flexible curriculum, students use it to advantage in an educationally responsible manner. PMID- 1497787 TI - Women physicians in dual-physician relationships compared with those in other dual-career relationships. AB - This study compared the career and domestic responsibilities of women physicians whose domestic partners were physicians (WP-Ps) with those of women physicians whose domestic partners were not physicians (WP-NPs). In 1988 the authors surveyed 602 women physicians in a large midwestern city regarding their career and domestic roles; 390 were physicians in training (students and residents), and 212 were physicians in practice (academic medicine and private practice). Overall, 382 (63%) responded; of the 382, 247 (65%) had domestic partners; of these 247, 91 (37%) were WP-Ps and 156 (63%) were WP-NPs. The WP-Ps were found to be twice as likely as the WP-NPs to interrupt their careers to accommodate their partners' careers. The WP-Ps also assumed significantly more domestic responsibilities and worked fewer hours practicing medicine than did the WP-NPs. The 163 women physicians in training (44-48%-of the WP-Ps and 119-76%-of the WP NPs) demonstrated a more egalitarian division of labor overall, with no significant differences between the WP-Ps and the WP-NPs. The authors recommend that longitudinal studies be undertaken to determine whether women physicians in training continue this trend as they enter the practice of medicine. PMID- 1497789 TI - Consultative and educational roles of a physical therapist in a family practice residency. AB - Many medical schools and primary care residencies provide little formal instruction in musculoskeletal examination skills. Physical therapists are well qualified by knowledge and experience to teach these skills to students and residents. The authors present educational objectives that have been utilized since May 1988 in the physical therapy teaching portion of a sports medicine rotation in a family practice residency, and they describe the educational and consultative roles of a physical therapist in the residency. The therapist demonstrated the portion of the musculoskeletal examination that is important for the differentiation of contractile and inert tissue involvement, and she reviewed problems unique to athletes. The therapist's presence exposed students, residents, and faculty to the appropriate use of physical therapists as consultants and clinicians. PMID- 1497791 TI - Utility of the sickness impact profile in Parkinson's disease. AB - The Sickness Impact Profile (SIP) is a questionnaire consisting of 136 items grouped into 12 categories and two dimensions (physical and psychosocial). To characterize its utility in Parkinson's disease (PD), we administered the SIP to 44 consecutive clinic patients with PD. Compared to 44 age- and sex-matched control subjects, PD patients had their greatest dysfunction in the categories of mobility, communication, and home management. The two items that PD patients most commonly endorsed were, "I am having trouble writing or typing" (75%) and, "My sexual activity is decreased" (61%). In general, these treated PD patients had greater dysfunction in the psychosocial than physical dimensions. Two simple PD specific scales correlated well with the physical dimension score but less so with the psychosocial dimension, suggesting that the SIP assesses more functional domains than the PD-specific scales used. The SIP holds some promise as a broad measure of functional status in PD patients. PMID- 1497790 TI - Alzheimer's disease: a model from the quantitative study of a large kindred. AB - In an Italian kindred (family N), early onset Alzheimer's disease has been transmitted in a Mendelian autosomal fashion since the early 18th century. The age at death of affected members of the family varies widely, and was taken as an index of the age of expression, a measure of phenotypic variability. Either a gamma or a log-normal algorithm provides the best fit for the age at death distribution. Subsets of family N widely different as to time and place have the same age at death of patients: Environment appears to play a negligible role in the expression of disease. Pairwise correlation between an affected parent and child is zero: The disease is monogenic (no major expression gene). The same stochastic distribution of age of expression, but with late onset, and after correction for death from other causes, is compatible with the epidemiology of Alzheimer's disease in general. Mendelian genetics is a possible model for Alzheimer's disease etiology. PMID- 1497792 TI - ECT-induced interictal delirium in patients with a history of a CVA. AB - Earlier works have documented a high incidence of affective disorders in patients with a history of a cerebrovascular accident (CVA). In general, electroconvulsive therapy (ECT) has been reported to be effective in treating depressed patients with a history of CVA. Recent works have shown that preexisting structural brain changes may predispose patients to develop interictal ECT-induced delirium. However, the incidence of ECT-induced interictal delirium in patients with a history of CVA has not been directly studied. In this pilot study, the authors examined the incidence of ECT-induced interictal delirium in 14 depressed CVA patients compared with 14 elderly depressed controls (without a history of CVA). Interestingly, the overall incidence of delirium was identical in both groups (28.5%). However, consistent with previous works, some patients who had had a recent CVA involving the caudate nucleus appeared more likely to develop delirium. Thirteen of the 14 depressed CVA patients (92%) showed a moderate to significant improvement in their depressive symptoms from ECT. None of the patients developed significant cardiac complications during ECT. PMID- 1497793 TI - Population-based dementia screening program in Kuopio: the effect of education, age, and sex on brief neuropsychological tests. AB - A neuropsychological screening battery including the Mini-Mental State Examination and four other brief cognitive tests (Russell's Adaptation of the Visual Reproduction Test, Trail Making Test, Verbal Fluency Tests on letters and category, and the Buschke Selective Reminding Test) was administered to a randomly selected population sample of 403 subjects aged 68 to 77 years to evaluate the effect of education, age, and sex on test scores. The difference in neuropsychological screening tests between various education groups (3 years or less, 4 to 6 years, 7 years or more) was statistically highly significant, even after the adjustment for the effect of age. The subscores and total scores were lowest in the minimal education group on every neuropsychological test. Education correlated more strongly than age with all neuropsychological test scores and subscores. The effect of sex on test results was seen only in some subscores of brief neuropsychological tests but not in a single item of the Mini-Mental State Examination. On the basis of our results, the effects of education, age, and sex have to be evaluated before using brief neuropsychological tests in population based dementia screening. PMID- 1497794 TI - Subclinical dementia: relevance of cognitive symptoms and signs. AB - In 1971 and 1972, a representative sample of 70-year-old people (n = 392) from a population study was rated with regard to psychiatric symptoms and signs. Subjects showing evidence of dementia of any degree, including slight and questionable, were excluded (n = 18). The remaining 374 subjects were followed longitudinally for 9 years. Thirty-eight subjects developed severe dementia during this period. They were compared to those who did not with regard to 19 reported and 17 observed items concerning general psychopathology, seven reported items concerning sleep, and a global rating of mental health. Five items correlated with the development of severe dementia: number of remembered dreams per week, latency of speech, speed of speech, difficulties in finding words, and memory for recent events. A stepwise logistic regression procedure demonstrated that a low frequency of remembered dreams, a reduced memory for recent events, and difficulties in finding words made independent contributions to the prediction of dementia. There were no differences with regard to affective items. There were no differences between the subjects who developed senile dementia of the Alzheimer type and those with multi-infarct dementia. The results thus support the hypothesis that symptoms pertaining to cognitive functions are the first to appear in the development of dementia. PMID- 1497795 TI - [Local immunological phenomena in the digestive system of the child and food allergy]. AB - Over the last few years food allergies have become a clinical problem of prime importance in children. It is clear that food allergy is most frequent in infants. Food macromolecules are absorbed at every age, but most evidently during the first months of life. Many facts show that the barrier of the gastro intestinal tract against harmful agents present in the intestinal lumen is not completely developed in infants and especially in newborns. Deficiencies in the secretory system for TgA contribute to greater permeability of the intestine for allergenic macromolecules in early childhood. PMID- 1497796 TI - [Allergy to heparin. Particular problems in the pregnant woman]. AB - Oral anti-coagulants are always contra-indicated for pregnant women. Only anti coagulants of the types of heparin or its derivatives may be used. However, some patients have an allergy to Heparin. In this article the correct action to take both for diagnosis and prevention is studied. We present 2 observations of heparin-allergic pregnant women with, in the first case a tentative addiction to heparin which created a check and in the second case there was success in a second pregnancy with low-molecular weight heparin. PMID- 1497797 TI - [Spatial and temporal variations of the quantities of pollen from Cupressaceae Taxaceae collected in Marseilles]. AB - Marseille has two sites (Centre and North) where airborne pollens are collected and counted. The most numerous pollens are from Cupressaceae Taxaceae. We compared the quantities collected with both pollen traps during February, March and April 1988 and 1989. Most of pollinization takes place in March. In Marseille's Centre, there were three times more trapped pollen during 1989 than in 1988. In 1989, there was 40% more pollen on northern site as compared with the other one. As indicated in 1989 with both sites, it suggests a circadian periodicity of Cupressaceae Taxaceae pollen: their highest count is usually between 9 and 11 hours a.m. PMID- 1497798 TI - Patient education programmes in obstructive airway disease. The Ingelheim Model for promoting health through patient education. AB - Chronic obstructive airway diseases (COAD) can be regarded as one of the major health problems needing environmental actions and screening programs for early detection and intensive patient education programs to cope with the needs of tertiary prevention. On the basis of our epidemiological study focused on COAD carried out in FRG (sample size August 1988: 63,000 participants) a patient education program has been developed and evaluated. In cooperation with general practitioners and pneumologists the program has been installed at practice and community level. The need for a patient education program has been assessed during the three years of the PNEUMOBIL-Project. It is not just a matter of cutting costs, but to a large extent a matter of the wellbeing of the patients and of reducing side effects to a minimum. The objective of the project can be split into three dimensions: (1) The cognitive aspect. Here significant lack of knowledge has to be overcome. At this point it has to be stated clearly that at the present time the medical community is not able to solve this problem on their own. (2) The psychomotoric aspect. Here the competent use of medication has to be trained. (3) The emotional aspect. The patient has to be motivated and integrated into the therapeutic process in a way that his compliance contributes significantly. The didactical concept consists of modules that can be used in varying sequences according to the needs of the target audience.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1497799 TI - Toxicity was defined as any deleterious change that was discerned by histopathology. PMID- 1497800 TI - p53 gene mutations in human endometrial carcinoma. AB - Although carcinoma of the uterine endometrium is the most frequently diagnosed malignancy of the female reproductive tract, the molecular genetic features of this tumor have yet to be described in significant detail. Since mutations of the p53 tumor suppressor gene are the single most common genetic alteration found in human malignancies, we examined the hypothesis that p53 mutations occur in human endometrial carcinoma. Sequencing analysis of exons 5-8 revealed point mutations in 3 of 21 (14%) tumors; one mutation was an unusual single-base insertion at codons 176-177, resulting in a premature stop codon, whereas the other two were CGG----TGG transitions at codon 248. Two of these tumors showed reduction to homozygosity at the p53 allele, but one tumor apparently retained heterozygosity. These data indicate that p53 mutations occur in human endometrial carcinoma, although relatively infrequently, and that loss of the normal p53 allele does not necessarily occur with point mutation of the p53 gene in this tumor type. PMID- 1497801 TI - Characterization of the Syrian hamster c-Ha-ras gene and intron-D-exon transcript. AB - The coding sequences as well as 5'- and 3'-flanking sequences of the Syrian hamster c-Ha-ras gene were deduced from cDNA clones derived from embryo fibroblast cell lines. Sequences of introns B, C, and D were obtained from genomic DNA after amplification by the polymerase chain reaction. Sequence comparisons with rat, mouse, and human c-Ha-ras genes revealed a high degree of homology. One of 12 cDNA clones contained intron-D-exon (IDX) sequences due to alternative splicing that would encode a p19 Ha-ras gene product. Conservation between species suggests a functional role for the IDX, possibly as a negative control of p21 Ha-ras expression. PMID- 1497802 TI - Activating mutation of the Ha-ras gene in chemically induced tumors of the hamster cheek pouch. AB - The presence of an activating mutation in the Ha-ras gene in hamster cheek pouch tumors induced by 7,12-dimethylbenz[a]anthracene (DMBA) complete carcinogenesis was investigated. The normal sequence of a fragment of genomic DNA encompassing codon 61 of the Ha-ras gene was amplified by the polymerase chain reaction using primers designed for a highly conserved region of the mouse Ha-ras-1 gene. The sequence of the amplified fragment was determined by a direct sequencing technique and exhibited 83.3% and 87.5% homology with the corresponding human and mouse sequences, respectively. At the amino acid level, the sequence was identical among the three species. Paraffin sections of 11 squamous cell carcinomas of the cheek pouch were used to detect mutated Ha-ras alleles. DNA sequencing of the tumors showed that six of 11 tumors presented an A----T transversion in the second position of codon 61, resulting in an amino acid change from glycine to leucine. As has been demonstrated in other systems, we have shown a specific mutation of the Ha-ras gene in chemically induced tumors of the hamster cheek pouch, further supporting the role of this oncogene in chemical carcinogenesis. PMID- 1497803 TI - Evidence for coincident mutations in human lymphoblast clones selected for functional loss of a thymidine kinase gene. AB - A mitotic "recombination-competent state" inducible by x-irradiation is thought to exist in yeast. We sought evidence for such a process in mammalian cells by examining the occurrence of mutations at unlinked loci in clones derived from a human lymphoblast cell line. A total of 169 independent clones that arose spontaneously or after exposure to x-rays or ethyl methanesulfonate were selected for new somatic mutations at the thymidine kinase gene on chromosome 17q. They were subsequently screened for coincident mutations by use of variable-number-of tandem-repeat probes located on different chromosomes. Three coincident mutations were positively identified by Southern analysis on chromosomes 7 and 14; they included one that produced a new allele and two that caused loss of allele heterozygosity. Densitometric analysis of the latter two indicated the presence of two copies of the remaining allele. Several possible coincident genetic events were also observed on chromosome 17. These findings revealed a coincident mutant fraction of about 10(-2)/cell, whereas the expected mutation fraction at these loci is less than 10(-4)/cell. These results may thus provide the first molecular evidence that a "global" mutational process capable of inducing genetic instability exists in mammalian cells. PMID- 1497804 TI - Differential retention of tumor- and differentiation-suppressor functions in cells derived from a human squamous cell carcinoma. AB - Three morphologically distinct cell lines--F.2a, V, and B.2--were isolated from a single human squamous cell carcinoma. Although all three cell lines can grow indefinitely in culture, they differ in a number of important transformation related phenotypes. Only B.2 is strongly tumorigenic when injected into the flanks of nude mice, and only V can efficiently grow in semisolid media. The dominance of these traits was investigated by generating somatic cell hybrids among the three cell lines. F.2a was able to suppress the tumorigenicity of B.2 cells, whereas B.2 inhibited the capacity for anchorage-independent growth of V, the latter trait being a function of the ability of these epithelial cells to differentiate when deprived of support. The influence of exogenously added growth factors was also evaluated. This study indicates that the particular tumor we examined consisted of a heterogeneous population of cells with distinct growth and differentiation capacities. PMID- 1497805 TI - Approaches to patient and family education for pressure ulcer management. AB - The Agency for Health Care Policy and Research (AHCPR) guidelines for pain management, urinary incontinence, and pressure ulcers emphasize the importance of patient and family education. Patient teaching strategies are discussed by using the example of pressure ulcer management. The family is invited into an educational partnership through needs assessment and mutual goal setting. Teaching strategies that involve the learner and are adapted for the home setting are most effective. Evaluation of teaching should be in terms of patient outcomes. PMID- 1497806 TI - Photographing pressure ulcers to enhance documentation. AB - Complete and careful observation, description and documentation of pressure ulcers is an essential component of practice when caring for people with pressure ulcers. Photographing pressure ulcers and including the photo as part of the patient's chart provides a useful adjunct to the written record. While a "picture is worth a thousand words," photographs can be misleading unless they are consistently taken according to specific guidelines. Techniques to enhance photographic results and avoid common errors are discussed. PMID- 1497807 TI - Pressure ulcer risk assessment--simple or complex? AB - A descriptive comparison study was carried out to determine whether there was a difference between a staff nurse's single-item pressure ulcer risk assessment and a risk assessment using the Braden Scale. Seventy-two medical patients participated in the study. Statistical analysis of the data indicated nurses were accurate in predicting pressure ulcer risk with a simple YES/NO answer. The mean Braden Score for those patients indicated at risk by the nurse was 14.45, and 20.24 for those assessed to be not at risk. This study indicates that nurses' good judgement is as reliable as more complicated tools in determining pressure ulcer risk. Further studies comparing risk assessment tools are recommended. PMID- 1497808 TI - Teaching the assessment of patients with pressure ulcers. AB - Teaching assessment of patients with pressure ulcers involves the teaching of assessment of the total person as well as at-risk potential, daily examination of skin, and accurate assessment of progress or regression of a pressure ulcer. Suggestions and references are provided for teaching each of these aspects of assessment. PMID- 1497809 TI - Whose life is it? PMID- 1497810 TI - Sharing forms that helped decrease pressure ulcers. PMID- 1497811 TI - [Function differentiation]. PMID- 1497812 TI - [Project 'Function Differentiation Intramural Nursing']. PMID- 1497813 TI - [A survey: function differentiation in psychiatric hospitals]. PMID- 1497814 TI - [Coming changes: function differentiation in the care for mentally retarded]. PMID- 1497815 TI - [Competence level and complexness of care--function differentiation in general hospitals]. PMID- 1497816 TI - [The Amsterdam model. Interview by Tonny van de Pasch]. PMID- 1497817 TI - [The start of 2 levels of competence--from the viewpoint of professional content and organization]. PMID- 1497818 TI - [From Professional Profile to Functional Profile--theory translated for practice]. PMID- 1497819 TI - [A function profile for nurses--voluntary or compulsory?]. PMID- 1497820 TI - [Competence levels in nursing: the American experience]. PMID- 1497821 TI - [Welfare of the employee. Function differentiation and the quality of work]. PMID- 1497822 TI - The integration of radiotherapy into the primary treatment of non-Hodgkin's lymphoma. PMID- 1497823 TI - Liposomes in the treatment of malignancy: a clinical perspective. AB - Technological advances in liposomal preparation and efficient drug entrapment, along with supportive preclinical studies, have led to a number of recent clinical trials utilizing liposomes as drug carriers in the treatment of human malignancy. Although the results of these trials must be considered preliminary, it is clear that liposomal delivery of chemotherapeutic agents is safe at the doses administered. Aside from minor constitutional symptoms, virtually all toxicity could be attributed to release of the incorporated drug. Myelosuppression tends to be the dose-limiting toxicity with free drug, whereas constitutional symptoms are more likely to occur with encapsulated biologic therapy. Prior to human trials, there was fear that intravenous injection of liposomes could result in pulmonary emboli. No cases of pulmonary embolism secondary to liposome therapy have been recorded. The objective response rate in the patients studied appears to be minimal. This is not surprising, since the overwhelming majority of patients studied had disease that was advanced and previously shown to be refractory to therapy. Subgroups of patients that appear to benefit most include those with breast cancer who were treated with liposomal doxorubicin and those with advanced melanoma treated with liposomal tumor vaccines. Additional phase II and III clinical trials will better define the effectiveness of treatment modalities incorporating liposomes. VI-A. Future directions One of the earliest applications of liposomes may be in the amelioration of drug toxicity. Although not yet proven, the clinical studies reviewed suggest that liposomal delivery of doxorubicin reduces cardiotoxicity without sacrificing antitumor effect. Although similar claims have been made in support of continuous infusion doxorubicin [11], one can avoid unnecessary hospitalization or the bulk and expense of portable infusion devices by a single administration of the liposomal preparation. Liposome encapsulation can markedly alter the biodistribution and pharmacokinetics of well-known chemotherapeutic agents. The effectiveness of liposomal drug delivery in human trials thus far has probably been more closely related to altered pharmacokinetics rather than enhanced drug delivery to tumor or increased tumor responsiveness. As demonstrated by Gabizon [19], increased liposome circulating time in the murine model can be achieved by using small unilamellar vesicles containing a phosphatidylcholine of high phase-transition temperature and a small molar fraction of monosialoganglioside or hydrogenated phosphatidylinositol.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1497824 TI - Nutritional support of the child with cancer. AB - The purpose of this article is to outline how the disease, treatment, and psychological state of a child with cancer impact on the child's nutritional status. The methods of assessing nutritional status, including anthropometric measurements, laboratory indices, clinical observation, dietary assessment, and psychosocial evaluation, are summarized. After nutrition assessment, the pediatric oncology nurse and the dietitian, along with the oncologist, the family, and the child, develop a plan of care. The specific roles of the pediatric oncology nurse and dietitian in the nutrition intervention are described. PMID- 1497825 TI - Pain in the pediatric oncology patient. AB - Pediatric oncology nurses face many challenges in treating the pain associated with childhood cancer. The type and severity of pain children with cancer experience varies from acute, short-term, procedure-related pain to the progressive chronic pain associated with terminal illness. In addition, the unfounded fears of using strong narcotic analgesics and the underutilization of psychological techniques to treat pain in children limit the effectiveness of pain management. Armed with objective data, pediatric oncology nurses can work with other members of the cancer treatment team to provide relief from the pain associated with the diagnosis and treatment of childhood cancer. PMID- 1497826 TI - Nursing research--moving forward through networking, collaboration, and mentorship. AB - Numerous pediatric oncology nurses have provided the specialty with research that has established a foundation for the nursing care of children and adolescents with cancer. The research committee within APON is committed to facilitating further research development among pediatric oncology nurses. Research growth within APON will continue with the development of precongress research workshops for nurses interested in developing research projects, an advanced nursing research session to be held at the next national conference, and the organization of networking among pediatric oncology nurse researchers. Additionally, the research column will provide nurses with a review of the research process over the next several issues. Knowledge building is an evolving, dynamic process that is rapidly changing due to the newness of the specialty. As the pediatric oncology specialty continues to grow, networking, collaboration, and mentorship must become the keys to facilitating future research growth within APON. PMID- 1497827 TI - Midazolam for outpatient sedation. PMID- 1497828 TI - Human immunodeficiency virus infection in children--a guide for families. PMID- 1497829 TI - Holding up. PMID- 1497830 TI - Gastrointestinal manifestations in the child with cancer. AB - Pediatric oncology nurses provide a major role in the assessment and management of gastrointestinal complications in children resulting from cancer therapies. The clinical problems most frequently seen in this area include stomatitis, nausea, vomiting, constipation, and diarrhea. These areas are reviewed in detail according to various nursing diagnoses including definitions and pathophysiology, recent studies and interventions, special considerations for children, and patient and parent education. PMID- 1497831 TI - The future of dentistry. PMID- 1497832 TI - The future of endodontics. PMID- 1497833 TI - The future of implantology. PMID- 1497834 TI - A clinician's dilemma: when to bond, when to veneer. PMID- 1497835 TI - Intraoral video camera systems. PMID- 1497836 TI - A clinician's concept of post operative sensitivity in crown and bridge. PMID- 1497838 TI - Controlling financial arrangements in your practice. PMID- 1497837 TI - Smile Design Workshop. 7. Utilizing color in smile design. PMID- 1497839 TI - The welcome package: a must for new patients. PMID- 1497840 TI - Expert sets goals for geriatric dentistry. PMID- 1497841 TI - Long-term periodontal maintenance. PMID- 1497842 TI - Endodontic technology overlooked by dentists. PMID- 1497844 TI - Restoring the pulpless tooth. PMID- 1497843 TI - The role of the hygienist in the maintenance of aesthetic restorations. PMID- 1497845 TI - Repairing cervical fractures using adhesive cement. PMID- 1497846 TI - Direct flexible ceramic bonding. PMID- 1497848 TI - Patient retention. PMID- 1497847 TI - Computers and staff relations. PMID- 1497849 TI - Minerals and trace elements in milk. AB - The nutritional roles, requirements, and metabolism and the quantitative relationship between dietary intakes and health for a number of the minerals and trace elements have been more clearly defined in recent years, but there are still considerable deficiencies in our understanding of these issues, e.g., the significance of calcium in the etiology and treatment of osteoporosis and hypertension. Reliable information is now available on the content, and the principal factors affecting it, of most of the minerals and trace elements in human and cow's milks. However, for some of the trace elements, there is still a wide variation in reported values in the literature, which is due, at least in part, to analytical difficulties. The contribution of cow milk and milk products to the diet in Western countries is significant for sodium, potassium, chloride, calcium, phosphorus, zinc, and iodine. Iodine is the only trace element for which there has been any suggestion of excessive amounts in cow milk. However, there is evidence of a decline in milk iodine concentrations in the United States in recent years, although the situation in other countries less clear. Breast milk usually has adequate mineral and trace element contents for feeding full-term infants, with the exceptions of fluoride, for which supplementation of infants is recommended, and of selenium in some countries, such as Finland and New Zealand, where maternal intakes are low. However, breast milk selenium contents have increased in these countries in recent years due to increased maternal selenium intakes. The concentrations of minerals and trace elements in infant formulas for full-term infants are generally higher than in human milk, and all appear to be more than adequate, with the possible exception of selenium, which may need to be increased in some formulas. Considerable changes in the mineral and trace element contents of formulas have been instituted in recent years in the light of improved knowledge of infant requirements. While the chemical forms of the macrominerals and some of the trace elements (iron, zinc, copper, and manganese) in milks are fairly well defined, the forms of many of the trace elements are unknown. Sodium, potassium, chloride, and iodine are believed to be almost totally absorbed from milks and infant formulas.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1497850 TI - Dietary fatty acids, lipoproteins, and cardiovascular disease. AB - Dietary fat quality and quantity significantly affect the metabolism of all the plasma lipoproteins and probably constitute the most significant dietary determinants of plasma lipoprotein levels. Since the major role of the plasma lipoproteins is the transport of exogenous and endogenous fat, this would be expected of a highly regulated, metabolically homeostatic system. The data clearly show that dietary fat saturation affects all aspects of lipoprotein metabolism, from synthesis to intravascular remodeling and exchanges to receptor mediated and nonspecific catabolism. The experimental data regarding dietary fatty acid effects on lipoprotein metabolism are complicated and at times contradictory due to the large degree of metabolic heterogeneity in the population, which, when coupled with the known abnormalities of lipoprotein metabolism associated with certain types of hyperlipoproteinemia, can present responses from A to Z. It is clear that the same dietary pattern has different effects in different individuals and that complicating factors of individuality raise some concerns regarding generalized dietary recommendations. As new knowledge of the role of dietary factors and CVD risk develops, and our abilities to characterize the individual patient's response to dietary interventions become more refined, it may be possible to specify dietary fat intervention from a patient-oriented concept rather than a single all-purpose diet approach. Thus it would be possible to design dietary interventions to match patient needs and gain both efficacy and compliance. With the spectrum of approaches possible--low fat, moderate fat with MUFA, n-3 PUFA, etc.--we should be able to approach dietary interventions to reduce CVD risk at both a population-based level and a patient specific level. There remains much to learn regarding the effects of dietary fatty acids on the synthesis, intravascular modifications, and eventual catabolism of the plasma lipoproteins. The area of lipoprotein metabolism in health and disease, of its modifications by diets and drugs, and of the contributions of genetic heterogeneity to these processes is one of notable advances over the past two decades and continues to be an area of intense investigation. PMID- 1497851 TI - Plant food protein engineering. PMID- 1497852 TI - Metabolism of drugs: a reappraisal. AB - The paper deals with an up-to-date reappraisal of the most relevant aspects connected to the investigation of drug metabolism including the most appropriate methods used in preclinical and clinical field. Renal and biotransformation clearance is considered with several specific references. Reversible metabolism, active metabolites of drugs, various kinds of first pass effect, genetic polymorphism in drug metabolizing enzymes, the most appropriate pharmacokinetic analysis and regulatory aspects are the main aspects focused on. PMID- 1497853 TI - [A host system for genetic cloning: Saccharomyces cerevisiae]. PMID- 1497854 TI - Are eukaryotic ribosomes heterogeneous? Affirmations on the horizon. PMID- 1497855 TI - Origin of the two mRNA species for the human neurofilament light gene. AB - The human neurofilament light (hNF-L) gene yields two major species of mRNAs of 2.4 and 3.8 kilobases (kb) in size. To investigate the origin of these two mRNAs, we have analyzed in transgenic mice the expression of hNF-L DNA fragments including different lengths of 5'-flanking regions. The finding that the 3.8-kb mRNA species is produced by a hNF-L transgene that includes only the proximal promoter region (-0.3 kb) demonstrates that both the 2.4- and 3.8-kb mRNAs are derived from the same site of transcription initiation. Sequencing of the 3' untranslated region of the hNF-L gene revealed the presence of multiple AATAAA polyadenylation signals. We conclude from Northern blotting experiments using probes spanning various regions of the hNF-L gene that the 2.4- and 3.8-kb mRNAs originate from the selective use of polyadenylation signals located 1.4 kb apart. PMID- 1497856 TI - Identification of proteins potentially involved in proximal-distal pattern formation in the regenerating forelimb of the newt. AB - We have used high resolution two-dimensional gel electrophoresis to identify and characterize proteins that may represent products of genes involved in establishing positional information along the proximal-distal axis of the regenerating forelimb of the newt Notophthalmus viridescens. At least 24 proteins have been found whose synthesis and (or) abundance is increased in proximal (midstylopodial) regenerates relative to midzeugopodial (distal) regenerates at either of two regeneration stages, the early dedifferentiation and moderate bud stages. Four of these same proteins show an axial asymmetry at both stages. Ten distal-specific proteins were also identified, although only one was common to both stages. More significantly, 6 of these 34 proteins (molecular masses of 73, 73, 51.5, 44.0, 19.5, and 16.5 kilodaltons and isoelectric points of 6.70, 6.74, 6.0, 6.05, 5.9, and 6.98, respectively) are regulated to proximal levels by treatment of distal regenerates with retinoic acid (RA) at both stages. An additional five are proximalized by RA at only one regeneration stage. Since the effect of RA is to proximalize positional information in blastema cells, these 11 proteins represent gene products that could be involved in a biochemical cascade leading to the establishment of positional information in the regenerating limb along this axis. PMID- 1497857 TI - Visualization of a mammalian transcription initiation complex. AB - Various proteins required for the initiation of eukaryotic gene transcription by RNA polymerase II have been identified and characterized, but little is known about their organization into a functional unit. Here, we describe the appearance of the murine ribosomal protein (rp) L32 gene transcription initiation complex as determined by transmission electron microscopy. Using a fractionated nuclear extract enriched for transcription factors necessary for rpL32 gene transcription in vitro and a DNA fragment containing the rpL32 gene promoter, the transcription initiation complex was imaged by standard transmission electron microscopy. Quantitative image analysis demonstrated that the complex is a multilobed structure whose two-dimensional projections are approximately 24 x 34 nm in size. Looping of the DNA seen in these images suggests that the proteins residing at the promoter region associate with proteins several hundred base pairs distant to the RNA start site, with bending of the DNA allowing these interactions to occur. PMID- 1497858 TI - Inhibitors of human immunodeficiency virus-1 protease. AB - We have shown that the interaction of pepstatin A with human immunodeficiency virus-1 protease (HIV-1 protease) can be characterized by a high-affinity mode (Ki = 478 +/- 27 nM), resulting in pure competitive inhibition of the hydrolytic activity of HIV-1 protease toward the fluorogenic substrate. Binding of pepstatin in this mode induces a blue shift in the endogenous fluorescence arising from the tryptophan residues in HIV-1 protease. This shift is maximal in the presence of 10 microM pepstatin. Haloperidol, in contrast, interacts with HIV-1 protease with weaker affinity (Ki = 19 +/- 1 microM) in a mode which results in pure noncompetitive inhibition of the hydrolytic activity of HIV-1 protease. Binding of haloperidol in this mode induces a red shift in the endogenous fluorescence arising from the tryptophan residues in HIV-1 protease. This shift is maximal in the presence of 200 microM haloperidol. Addition of both pepstatin and haloperidol at concentrations in the range of their Ki values results in additive inhibition of the hydrolytic activity of HIV-1 protease, as well as an additive effect on the tryptophan fluorescence of protease. However, at saturating concentrations of pepstatin and haloperidol, the effect of haloperidol was predominant, as measured by the changes in the intrinsic fluorescence of HIV-1 protease. PMID- 1497859 TI - Readthrough enhancement and promoter occlusion on the ribosomal genes of Xenopus laevis. AB - An RNA polymerase I termination site is found just upstream of the ribosomal gene promoter in mammals and amphibia. It has been suggested that this termination site may actively enhance ribosomal transcription in a process known as readthrough enhancement or that it may simply prevent the disruption of initiation complexes or promoter occlusion. There is, however, a consensus of opinion that the terminator is important for efficient ribosomal transcription. Here we have quantitatively investigated the relative importance of readthrough enhancement and promoter occlusion on the transcription of the microinjected Xenopus laevis ribosomal gene. The results show that, in this system, promoter occlusion is limited and terminator mutations predominantly affect readthrough enhancement. The terminator is shown to be unnecessary for the enhancer activity of the rest of the ribosomal spacer. Model calculations suggest that readthrough enhancement could be explained by polymerase recycling and that it may be unnecessary to postulate a specific mechanism of polymerase handover. PMID- 1497860 TI - Interfacial adsorption of simple lipid mixtures combined with hydrophobic surfactant protein from pig lung. AB - Hydrophobic pulmonary surfactant protein enriched in SP-C has been mixed in amounts up to 10% by weight with various phospholipids. The lipids used were dipalmitoyl phosphatidylcholine (DPPC), or DPPC plus unsaturated phosphatidylglycerol (PG), or phosphatidylinositol (PI) in molar ratios of 9:1 and 7:3. The protein enhanced the rate and extent of adsorption of each lipid preparation into the air-water interface, and its respreading after compression on a surface balance. Maximum surface pressures attained on compression of monolayers of mixtures of lipids were slightly higher in the presence of protein. The effects on rate and extent of adsorption were proportional to the amount of protein present. Mixtures containing 30 mol% PG or PI adsorbed more readily into the interface than those containing 10% acidic lipid or DPPC alone. Mixtures containing 30% PI were slightly more rapidly adsorbed than those containing 30% PG. The results suggest that mixtures of DPPC with either acidic lipid in the presence of surfactant protein could be effective in artificial surfactants. PMID- 1497861 TI - Compensatory effect of distal promoter sequences on the basal expression of a microinjected 70-kilodalton heat shock protein gene after the midblastula transition of Xenopus laevis embryogenesis. AB - The promoter sequences involved in the basal expression of a human 70-kilodalton heat shock protein (HSP70) gene during Xenopus embryogenesis were analyzed by microinjection of mutant promoters of a HSP70--chloramphenicol acetyltransferase fusion gene into fertilized eggs and following their expression during early development. While deletion of the HSP70 gene promoter to--100 base pairs (bp) did not affect basal transcription in postmidblastula stage embryos, linker scanner mutations in the CCAAT and purine box elements blocked expression. However, extension of the 5' boundary to--188 bp restored full wild-type expression to these mutants. These results suggest that multiple redundant cis acting regulatory elements present in the human HSP70 gene promoter can function during Xenopus embryogenesis. PMID- 1497862 TI - The ability of bovine mammary tissue to synthesize lipids for 96 h when cocultured with liver and adipose tissue. AB - Explants of bovine mammary, liver, and adipose tissues were cocultured in the same well for 24, 48, 72 or 96 h and their ability to synthesize lipids was measured by the incorporation of [14C]acetate into triglycerides, free fatty acids, and phospholipids. The model was developed to study the effect of bovine somatotropin on lipid synthesis in mammary tissue, because somatotropin will not affect mammary tissue unless liver tissue is present. Somatotropin reduced incorporation by mammary tissue relative to the control. However, the rate of incorporation remained constant through 96 h with somatotropin, but steadily decreased in control mammary tissue. Phospholipid release into the media increased dramatically from 2% of that synthesized during the first 24 h to 218% of that synthesized from 72 to 96 h. The high release of phospholipids after 24 h suggests that cellular breakdown was occurring. A 24-h incubation is recommended to study lipid synthesis with this system. PMID- 1497864 TI - Clinical effects of naltrexone on autistic behavior. AB - Eight young adults who were diagnosed with autism were given the opiate antagonist naltrexone to control self-injurious behavior and maladaptive idiosyncratic mannerisms. The drug and placebo were administered in a double blind crossover design over 17 weeks. Although one subject appeared to have partial decreases in maladaptive behaviors associated with naltrexone use, the drugs, as administered in this study, did not reduce the self-injurious and other maladaptive behaviors of the subjects. PMID- 1497863 TI - Factor analysis of the Chinese WAIS with persons who have mental retardation. AB - The Chinese revision of the WAIS (designated WAIS-RC) was factor analyzed for a sample of individuals with mental retardation. There were 55 Chinese subjects with a mean Full Scale IQ of 49.13 (SD = 16.46). Results indicated that a two factor solution comprised of the familiar Verbal Comprehension and Perceptual Organization factors best described the data. Comparison of the Chinese structure with that of a low-IQ Canadian sample tested with the American WAIS-R revealed congruence coefficients of .97 and .98 for Verbal Comprehension and Perceptual Organization, respectively. These findings provide support for further cross cultural research utilizing the latest editions of the American and Chinese Wechsler scales. PMID- 1497865 TI - Predictors of response to antidepressant medications. AB - In a 10-year interval, 175 residents of a state institution who had severe or profound mental retardation were treated with heterocyclic antidepressants when other medications and forms of treatment had proved ineffective. Responders to the medication were identified and compared with nonresponders to determine which presenting symptoms and other parameters might serve as predictors of medication efficacy. PMID- 1497866 TI - Haptic asymmetries in persons with and without mental retardation. AB - Adults with mild mental retardation and equal-MA children and adults without mental retardation were required to (a) tactually examine single letters, two letter words, bigrams, and Chinese characters with their right or left index finger and (b) indicate whether a visually presented stimulus was the tactually examined stimulus by saying "same" or "different." The left hand was significantly better for "same" responses and the right hand, for "different" responses, suggesting that hemispheric processing is dependent on information processing requirements rather than type of stimulus. A left hand advantage for "same" Chinese characters by the children and adults without mental retardation was due to an increase in right hand latencies rather than a decrease in left hand latencies, again suggesting that different types of analyses are employed by the two cerebral hemispheres. Adults with mental retardation had the poorest accuracy and slowest latencies for correct "different" responses and significantly less differentiation of "same" and "different" responses (A') for all stimulus types. They identified "same" letters, words, and bigrams significantly faster than Chinese characters with their left hand and showed a trend toward the differential processing of bigrams ("same" latencies) as a function of hand. PMID- 1497867 TI - Attentional resource demands of stimulus encoding for persons with and without mental retardation. AB - Speed of encoding differences between individuals with and without mental retardation were examined to determine whether they stem from an automatically executed cognitive process or from encoding processes that require attentional resources. In Experiment 1, encoding functions were generated for physical identity and name identity encoding while subjects retained a full memory load or half memory load. Size of memory load influenced encoding times for all subjects. However, the pattern of group differences suggested that subjects with mental retardation allocated fewer attentional resources to encoding, even though encoding may require more of their resources for efficient execution. These conclusions were supported in Experiment 2, in which resource allocation was assessed using response times to auditory probes placed at various locations in the semantic encoding and decision task. PMID- 1497868 TI - Localization of ras proto-oncogene expression during development in Xenopus laevis. AB - The expression of the ras protooncogene was investigated in Xenopus laevis, throughout development, by in situ hybridization using a 35S-labelled antisense RNA probe. During oogenesis, the ras RNA was strongly expressed in the cytoplasm of previtellogenic oocytes and further diluted between yolk platelets; no specific localization of transcripts was observed. The signal density was particularly weak over embryo sections until the tailbud stage. On the other hand, a high level of ras RNA expression was detected on sections through the young tadpoles. An intense labelling was observed in several areas, including the branchial apparatus, gut, somites, nervous system, and lens. It is noteworthy that the heterogeneity of labelling increases as tadpoles grow older. Together, these results are discussed in relation to cellular events appearing throughout the early development. PMID- 1497869 TI - Transcription of the H19 gene in differentiating cytotrophoblasts from human placenta. AB - Placental differentiation is closely correlated with the appearance of specific proteins, yet factors regulating cytotrophoblast differentiation are unknown. One strategy employed to search for such factors makes use of differential screening of cDNA libraries. For this purpose, cytotrophoblasts were isolated from human term placentae and cultured for 24 and 120 hr. cDNA libraries were constructed from the cell's RNA, and differential screening resulted in the isolation of three identical clones highly expressed after 120 hr. A DNA sequencing of 139 bp at the 3' end of these clones and a search of the data bank revealed that the sequence was identical to the parallel domain in the human H19 gene. This highly conserved gene is unusual in that it may not encode a protein. In the mouse, its RNA was shown to accumulate to high levels in embryonic tissues of endodermal and mesodermal origin. Our present findings imply that, in humans, the H19 gene is efficiently expressed in placental tissue and differentiated cytotrophoblasts, which are of ectodermal origin. RNA blot hybridization revealed a unique bimodal pattern of expression for the H19 gene in cultured cytotrophoblasts. The modulation in expression of H19 during cytotrophoblast growth was not due to the increase in the number of multinuclear cells. Size fractionation of cytotrophoblasts by centrifugal elutriation revealed that H19 expression is correlated with the stage of cell differentiation. We therefore propose that H19 transcripts might play a regulatory role in the process of cytotrophoblast differentiation. PMID- 1497870 TI - Construction of the nuclear matrix at the transition from maternal to zygotic control of development in the mouse: an immunocytochemical study. AB - The nuclear matrix is thought to be responsible for DNA organization, DNA replication, RNA synthesis, and RNA processing. We have looked for the presence of nuclear matrix antigens during early mouse embryogenesis. Antibodies to peripheral and interior antigens (P1, Pl1, Pl2, and lamin B) were used to immunolocalize nuclear matrix antigens in germinal vesicle oocytes, metaphase II oocytes, zygotes, two-cell-stage embryos, and eight-cell stage embryos. All antibodies reacted with the nuclei of germinal vesicle oocytes, and two- and eight-cell-stage embryos; however, only P1 and lamin B were present at the pronuclear stage. In eggs collected at the pronuclear stage and cultured to the late two-cell stage in the presence of alpha-amanitin, the matrix morphology was altered for Pl1 and Pl2. alpha-Amanitin had no affect on the distribution of P1 or lamin B antigens. If alpha-amanitin was added 2 hr after cleavage to the two cell stage, the normal staining pattern of Pl2 was retained. These results suggest that the presence of specific components of an internal matrix is correlated with normal genomic activity. PMID- 1497871 TI - The sperm entry site during fertilization of the zebrafish egg: localization of actin. AB - The sperm entry site (SES) of zebrafish (Brachydanio rerio) eggs was studied before and during fertilization by fluorescence, scanning, and transmission electron microscopy. Rhodamine phalloidin (RhPh), used to detect polymerized filamentous actin, was localized to microvilli of the SES and to cytoplasm subjacent to the plasma membrane in the unfertilized egg. The distribution of RhPh staining at the SES correlated with the ultrastructural localization of a submembranous electrondense layer of cortical cytoplasm approximately 500 nm thick and containing 5- to 6-nm filaments. Actin, therefore, was organized at the SES as a tightly knit meshwork of filaments prior to fertilization. Contact between the fertilizing sperm and the filamentous actin network was observed by 15-20 sec postinsemination or just before the onset of fertilization cone formation. Growing fertilization cones of either artificially activated or inseminated eggs exhibited intense RhPh staining and substantial increase in thickness of the actin meshwork. Collectively, TEM and RhPh fluorescence images of inseminated eggs demonstrated that the submembranous actin became rearranged in fertilization cones to form a thickened meshwork around the sperm nucleus during incorporation. The results reported here suggest that activation of the egg triggers a dramatic polymerization of actin beneath the plasma membrane of the fertilization cone. Furthermore, the actin involved in sperm incorporation is sensitive to the action of cytochalasins. PMID- 1497872 TI - Golden hamster embryonic genome activation occurs at the two-cell stage: correlation with major developmental changes. AB - The earliest time of onset of embryonic genome activation in golden hamsters was investigated. The inhibition of transcription by alpha-amanitin (11 micrograms/ml) in cultured embryos resulted in a total arrest of development of early 2-cell embryos (26 hr post-egg activation); under similar conditions, immediate cleavage divisions of 1-, late 2-, 4-, and 8-cell embryos were not affected. Electrophoretic analysis of [35S]methionine-labeled embryonic proteins showed that alpha-amanitin treatment apparently inhibited transcription-dependent protein synthesis in early 2-cell and, to some extent, in late 2-cell when compared to 4-cell embryos. Analysis of total RNA synthesis, using [alpha 32P] UTP or [32P]-orthophosphate, showed that there was a high proportion of radioactivity associated with the macromolecular fraction (RNA) at the early and late 2-cell stages and at the 4-cell stage compared to that at the 1-cell stage. These results indicate that the de novo synthesis of RNA, encoded by the embryonic genome, occurs at the 2-cell stage and that the second and subsequent cleavage divisions of hamster preimplantation embryos are dependent on new transcriptional activity. This initial activity of the embryonic genome in hamsters is coincident with several characteristic features of in vitro development such as a block to development, synthesis of major proteins, change in energy substrate preference, phosphate-inhibition of development and a requirement for amino acids. PMID- 1497873 TI - Primary culture of human fallopian tube epithelial cells and co-culture of early mouse pre-embryos. AB - We have established a monolayer culture system for human fallopian tube epithelial cells. The cells were isolated from tubes using collagenase digestion, and were cultured in Ham's F-10 supplemented with 15% fetal calf serum. The epithelial cells derived from culture were characterized using immunocytochemical staining and electron microscopy. These cells were stained with antikeratin and anti-epithelial membrane antigen, but showed no staining after treatment with antivimentin. Electron microscopy showed many microvilli on the cell surface and tight junctions or desmosomes at areas of cell-cell contact. Cell proliferation was enhanced by epidermal growth factor, but not by fibroblast growth factor, insulin, transferrin, estradiol-17 beta, or progesterone. The 2-cell ICR mouse pre-embryos were co-cultured for 4 days with tubal epithelial cells (A) (n = 98), in cell-conditioned medium (B) (n = 83), or in medium alone (C) (n = 72). During the first 24 h in culture, for groups A and B, the rates of cleavage to the 4 cell stage were 90.9% and 81.9%, respectively. Cleavage rates in these two groups were significantly higher (P = 0.0012, P less than 0.00001) than in group C (56.9%). After 72 h in culture, the rates of development to the blastocyst stage were significantly higher for groups A and B compared to group C (89.6% and 73.5% vs. 54.5%, P less than 0.00001, P = 0.0002). These results suggest that factor(s) from tubal epithelial cells may facilitate the development of mouse pre-embryos throughout the pre-implantation stages. PMID- 1497874 TI - Cleavage rate of diandric triploid mouse embryos during the preimplantation period. AB - The postimplantation development of human and animal triploid embryos is well documented, but there is little informative data on their preimplantation development. An analysis of cell number at appropriate times during this period and thus their cleavage rate would give an indication of the potential triploids have for further development and may explain some problems associated with their postimplantation development. To rule out any effects of technical procedures on cleavage rate, appropriate controls were used. Diandric triploid embryos were produced using standard micromanipulatory techniques, which involved the injection of a male pronucleus into a recipient one-cell-stage embryo. The karyoplast was fused to the cytoplasm by electrofusion, and the resulting tripronucleate diandric triploid embryos were transferred to appropriate pseudopregnant recipients. At specific times after the transfer, the embryos were recovered and cell numbers established. The results were plotted and regression lines drawn. Three controls were used 1) micromanipulated diploid embryos from which the male pronucleus had been removed and immediately reinserted and fused to restore diploidy, 2) diploid embryos that had been briefly incubated in cytochalasin D and colcemid to find out the effects these agents had on development, and 3) diploid embryos that had been isolated and briefly incubated in tissue culture medium. All embryos were subsequently transferred to recipients. After isolation at specific times during the preimplantation period, cell numbers were also established and the results plotted.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1497875 TI - Effect of electrofusion pulse in either electrolyte or nonelectrolyte fusion medium on subsequent murine embryonic development. AB - This study was designed to determine what effect electropulse parameters would have on rate of fusion, lysis, and embryo viability when embryos were subjected to electrofusion treatment in nonelectrolyte or electrolyte pulse media. Previous experiments have shown electrolyte medium (i.e., phosphate-buffered saline; PBS) to have a positive effect on electric pulse-induced murine oocyte activation. In addition, these results also indicated that pulse media containing 0.9 mM Ca2+ induced a dramatic increase in the rate of murine oocyte activation compared with oocytes pulsed in media containing 0.0 or 0.05 mM Ca2+. Pronuclear or two-cell stage embryos were obtained from superovulated prepubertal randomly bred Swiss (albino) female mice. Embryos were randomly assigned to three nonelectrolyte and three electrolyte treatment media. Nonelectrolyte media consisted of 0.3 M mannitol (T1), 0.3 M mannitol + 0.05 mM CaCl2 (T2), and 0.3 M mannitol + 0.9 mM CaCl2 (T3). Electrolyte media consisted of Ca(2+)-free PBS (T4), PBS containing 0.05 mM CaCl2 (T5), and PBS containing 0.9 mM CaCl2 (T6). Three experiments were carried out; the objective of the first was to determine the rate of fusion and rate of lysis in murine two-cell embryos placed in the two types of (0.3 M mannitol, T1-T3; and PBS, T4-T6) fusion media and subjected to a fusion procedure (3 V, 5 sec AC alignment pulse, followed by a 1.56 kV.cm-1, 99 microsec DC fusion pulse). Control two-cell embryos were placed in T1 for 2 min and did not receive a fusion pulse.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1497876 TI - Morphological development and sex of bovine in vitro-fertilized embryos. AB - Bovine in vitro-fertilized embryos at the blastocyst stage were collected at days 7, 8, and 10 postinsemination and sex was determined via the polymerase chain reaction (PCR) to compare the embryonic development with the sex of the embryos. The percentages of males (sex ratio) after division of the embryos into three developmental groups were 68%, 48%, and 35% in the fast, intermediate, and slow groups, respectively (P = 0.014). The percentages of males on days 7, 8, and 10 were 60%, 40% and 33%, respectively (P = 0.043). The average sex ratio for the whole material was 50%. It is thus concluded that male bovine preimplantation embryos develop faster than female embryos. PMID- 1497877 TI - Marsupial fertilization: some further ultrastructural observations on the dasyurid Sminthopsis crassicaudata. AB - Various morphological aspects of in vivo egg maturation and sperm-egg interaction were investigated in the Australian marsupial Sminthopsis crassicaudata with the transmission and scanning electron microscopes. Cortical granules invariably occurred in primary oocytes, with the number increasing after resumption of the first meiotic division. They generally occurred close to the oolemma, including the region near the oocyte nucleus. After mating, spermatozoa with intact acrosomes, which had a homogeneous electron-dense matrix, were found on the outer zona surface, but loss of acrosomal contents had occurred by the time of zona penetration. Sperm incorporation into the egg took place at the metaphase II stage of meiosis, and, at this time, cortical granules disappeared from the egg cortex. Sperm heads with condensed chromatin in the egg cytoplasm had an electron dense layer of subacrosomal material over part of the dorsal nuclear surface, but no membranes were present around these incorporated spermatozoa. Sperm chromatin decondensation resulted in an elevation of egg cytoplasm, and the cell membrane over this area lacked microvilli. The pronuclear envelope was not laid down until after chromatin decondensation had occurred. By this time the fertilized egg had reached the uterus, and a smooth, electron-dense, shell membrane had been deposited. These observations, together with our previous findings, indicate that some of the processes of sperm-egg interaction are similar to those in eutherian mammals, whereas others appear highly divergent. PMID- 1497878 TI - Synthesis and modification of D7 protein during Xenopus oocyte maturation. AB - The Xenopus maternal mRNA D7 is translationally repressed during oogenesis, only becoming recruited into polysomes during oocyte maturation, with D7 protein being detectable for the first time prior to germinal vesicle breakdown (GVBD). The synthesis of D7 protein was found to be induced by a variety of maturation promoting agents including cyclin, c-mos and crude preparations of MPF. D7 protein induced by all these agents is post-translationally modified and exists as a number of variants of differing molecular weight. In contrast to endogenous D7 mRNA, D7 RNA injected into the stage VI oocyte is efficiently translated, resulting in the accumulation of predominantly unmodified D7 polypeptides, which become increasingly modified during oocyte maturation to produce a pattern of polypeptides similar to those derived from endogenous D7 mRNA. Thus, the system that results in the post-translational modification of the D7 protein is itself activated during oocyte maturation. The nature of the protein modification is not known but does not appear to be phosphorylation. The translation of exogenous D7 RNA in the stage VI oocyte does not lead to translational derepression of endogenous D7 mRNA. PMID- 1497879 TI - Regulated temporal and spatial expression of the calcium-binding proteins calcyclin and OPN (osteopontin) in mouse tissues during pregnancy. AB - In situ hybridization and northern/slot blot analyses were used to quantify the expression of calcyclin (2A9, 5B10), osteopontin (opn, secreted phosphoprotein, 2ar) and calmodulin mRNAs in mouse tissues that support pregnancy. High-to moderate levels of the mRNAs of all three genes were detected at discrete locations in the uterus, decidua and placenta as a function of gestation time. Calmodulin expression was constant in these tissues; calcyclin mRNA was high during early pregnancy and declined after day 8-9 of gestation; and opn mRNA was undetectable before day 7, with maximal levels on days 9-12 in each of these tissues. Calcyclin, but not opn, expression was also observed in the chorioamnion after day 12. Calcyclin was expressed throughout the decidua on day 8 but became restricted to the primary (antimesometrial) decidual zone and decidua lateralis on day 9, and the decidua capsularis after day 9. By contrast, opn mRNA was localized on day 9 to the mesometrial triangle, which contains a large population of granulated metrial gland cells, and to the decidua basalis. These two genes may serve as markers for the two types of decidual tissue. We suggest that one function of OPN, which may be an indicator of cells in the decidua that have a bone marrow genealogy, is to mediate the flux of calcium from the maternal circulation to the developing embryo. PMID- 1497880 TI - Expression of interleukin-6 in porcine, ovine, and bovine preimplantation conceptuses. AB - A porcine interleukin-6 (pIL-6) cDNA has been cloned from pig spleen cDNA library to provide information that would allow us to study IL-6 mRNA expression during pregnancy of several domestic Artiodactyla. The cDNA is 1058 bp long and with a single open reading frame that encodes a 212 amino acid polypeptide with 28 residue signal sequence. It shares 61% and 43% amino acid sequence identity with human and mouse IL-6, respectively. PCR procedures with primers designed from regions of sequence conserved between human and pig have been used to identify IL 6 cDNA in lambda gt11 libraries constructed from day 15-16 (sheep), day 17 (cattle), and day 13-17 (pig) conceptus mRNA. The presence of IL-6 mRNA in elongating preimplantation ovine (days 13-25), porcine (days 13-21), and bovine (days 16-20) conceptuses was also demonstrated by PCR after reverse transcription of total ribonucleic acid with reverse transcriptase and by solution hybridization with a pIL-6 cRNA probe. These observations suggest that IL-6 is a product of these early conceptuses and may be involved in early maternal responses to the presence of an embryo within the uterus. PMID- 1497881 TI - Drop out: a third chromosome maternal-effect locus required for formation of the Drosophila cellular blastoderm. AB - drop out (dop) is a recessive maternal-effect locus identified in a screen for female-sterile mutations in Drosophila polytene region 71C-F. Phenotypic analyses of the dop mutation indicate that the gene is required for proper formation of the cellular blastoderm. In embryos derived from either homozygous or hemizygous dop mothers, cytoplasmic clearing, nuclear migration and division, and pole cell formation appear normal. However, developmental defects are observed prior to and during cellularization of the blastoderm. At the beginning of nuclear cycle 14, the distinct separation of the internal yolk mass and the cortical cytoplasm breaks down. Subsequently, a population of somatic nuclei located at the periphery of the syncytial blastoderm becomes irregularly spaced and nonuniform in their distribution. Despite a somewhat regular formation of the cortical actin network, cellularization in mutant embryos is extremely variable. Such embryos fail to gastrulate normally and produce variable amounts of defective cuticle. Overall, our analyses suggest that the dop gene functions in maintaining the separation of yolk and cortical cytoplasm and in stabilizing the distribution of somatic nuclei in the Drosophila syncytial blastoderm. PMID- 1497882 TI - Isolation of epiblast-specific cDNA clones by differential hybridization with polymerase chain reaction-amplified probes derived from single embryos. AB - A mouse day 7.5 embryonic ectoderm cDNA library containing 2 x 10(6) clones was screened by differential hybridization with polymerase chain reaction (PCR) amplified probes derived from a single embryo. Day 7.5 ectoplacental cone and embryonic ectoderm served as the source of mRNA to make minus and plus probes, respectively. In a limited screen of fewer than 2,000 clones, 23 up-regulated clones were identified by the difference in hybridization signal with the two probes. DNA sequence analysis revealed the nature of some, but not all, of the clones. Northern blot and in situ hybridization with a subset of the clones confirmed the utility of the approach, since the differential signal was also observed in these experiments. This approach may prove useful for identifying genes that play a role during development. PMID- 1497883 TI - Glycogen breakdown in cleaving Xenopus embryos is limited by ADP. AB - Xenopus eggs contain large stores of glycogen, but this glycogen is not glycolytically processed during cleavage. The Embden-Meyerhof pathway is inhibited by the absence of pyruvate kinase activity in vivo, and lactate and pyruvate are present at relatively low levels. In the late blastula, just preceding gastrulation, lactate levels increase, indicating the onset of glycogen breakdown and glycolytic flux. Glycolysis from microinjected [14C]glucose-6 phosphate could be transiently activated, however, by the coinjection of ADP into fertilized eggs, and constitutively activated by the injection of the ATPase potato apyrase, indicating the presence of all enzymes necessary for glycolytic activity. The isozyme profiles of pyruvate kinase and malic enzyme, two enzymes involved in carbon metabolism during cleavage or in the subsequent activation of glycogen breakdown, do not change between the egg and gastrula stages. These data suggest that the activation of glycogen breakdown and glycolysis in the late blastula is probably not a result of new gene activity but may be the metabolic consequence of increased free ADP that is then able to support the pyruvate kinase reaction. PMID- 1497884 TI - Prefertilization treatment of mice with platelet activating factor affects pregnancy. AB - Embryo-derived platelet activating factor (EPAF) is thought to be either biologically similar to platelet activating factor (PAF) or responsible for PAF liberation in vivo. We have previously shown that premating PAF treatment in the mouse renders the platelets nonresponsive to EPAF, leading to a reduced implantation rate in these animals. In this study, we have shown that females, injected with PAF before mating, show altered embryo development invivo on day 4 postfertilization. This is manifested as an interruption of compaction, a reduced cell number per embryo, and reduced embryo number per mouse. Results suggest that EPAF represents an early pregnancy signal that supports embryo development. The most likely mechanism is via platelet activation, since only those mice that showed thrombocytopenia after fertilization were found to have normal embryos on day 4 postmating. PMID- 1497885 TI - Migration of centromere proteins in rabbit spermatids. AB - Human autoantibodies were used to localize centromere proteins by immunoelectron microscopy, immunofluorescence, and confocal microscopy in isolated cells and in cryosections of rabbit testis. A computer-assisted three-dimensional reconstruction of the positions and sizes of fluorescent spots allowed us to follow their movements during the different phases of spermiogenesis. In very young spermatids, the centromeres were distributed within a space separated from both the external nuclear limits and the nuclear core. They moved towards the nuclear center in cap phase spermatids, where they clustered into a few large centromeric masses. In preelongating spermatids, the immunolabeled proteins were dispersed within an equatorial area, where they formed one large mass. In late spermatids, the mass moved towards the posterior part of the nucleus, and, in the spermatozoon, the two basal knobs located at the base of the nuclei were the only strongly immunolabeled structures, while no labeling of the main part of the nucleus was observed. Since the number of centromeres remained close to the number of chromosomes until the cap phase of spermatid differentiation, we hypothesize that the labeling of young spermatids corresponds to centrometric proteins associated with their specific DNA counterparts, while the centromere proteins, possibly detached from their DNA loci, were released from nuclei of old spermatids in the same way as are histones and transition proteins. PMID- 1497886 TI - Purification and characterization of a vitelline coat lysin from Ciona intestinalis spermatozoa. AB - In Ciona intestinalis a chymotrypsin-like activity is involved in sperm penetration of the egg vitelline coat. A chymotrypsin-like enzyme has been purified from spermatozoa by a protocol including ion exchange chromatography, gel filtration, and native polyacrylamide gel electrophoresis. The purified enzyme resulted homogeneous when analyzed by SDS-PAGE. The molecular weight of the chymotrypsin-like enzyme was estimated to be 35 kDa by gel filtration and 24 KDa by SDS-PAGE in nonreducing conditions. The pH optimum of the enzyme is 8.4 and its activity is enhanced by Ca2+. It shows the highest activity towards the synthetic substrate Suc-Ala-Ala-Pro-Phe-AMC. Furthermore, by electron microscopy, the purified enzyme affects the structure of egg vitelline coat, and thus it fulfills one of the criteria of a lysin. PMID- 1497887 TI - Collection of acrosome-reacted human sperm using monoclonal antibody-coated paramagnetic beads. AB - A monoclonal antibody (MAb) against human acrosome-reacted sperm was attached to paramagnetic polystyrene beads. Human sperm prepared by the swim-up method were 1) incubated in m-BWW, 2) incubated and ionophore treated, or 3) incubated with 5% seminal fluid. After treatment, sperm were mixed with the beads and incubated for 1 hr. Variously treated sperm showed different binding abilities to the beads. Sperm bound to the beads were collected by a magnet and subjected to triple staining. Most of the collected sperm were acrosome reacted. The results suggested that the beads can be used to estimate the acrosomal status of sperm, and that the use of antibody-coated paramagnetic beads provides a convenient way of collecting acrosome-reacted sperm. The acrosomal status detected by the beads was also compared with the ability of sperm to fuse with zona-free hamster eggs. It was found that greater bead-binding ability correlated with more sperm fusing with zona-free hamster eggs. PMID- 1497888 TI - Evidence for differential maturation of reciprocal sperm segregants in the murine Rb(6.16) translocation heterozygote. AB - The fertilizing ability of unaged sperm and those aged experimentally in the cauda by surgically ligating the corpus epididymis in males carrying the Rb(6.16) translocation was studied. Chromosomally normal females were inseminated with unaged sperm delivered by males mating at 3-day intervals, and aged sperm were studied after matings on 6-14 postoperative days. The sperm chromosome complement was analyzed in first-cleavage metaphase zygotes after sequential G- and C banding of the chromosomes. Of 283 metaphasic zygotes in the control group, 183 (or 64.7%) were analyzed and showed a ratio of 2.7:1 for chromosomally normal and balanced segregants of the translocation, deviating significantly (P less than 0.001) from the expected 1:1. The ratio of X- to Y-bearing sperm also deviated from expected (P less than 0.01) mostly due to a significant deficiency (P less than 0.05) of balanced sperm that were X-bearing. Fertilized oocytes were recovered from matings of 10 males on days 6-8 postoperatively, and, of 139 metaphasic one-cell zygotes, 101 (or 72.3%) were analyzed. These showed a Mendelian ratio of 1:1 for normal and balanced segregants. The sex ratio in the aged group (57Y:41X) also showed no deviation from 1:1. The results, which reveal significant physiological distortions for both the segregation and the sex ratios in males heterozygous for the Rb(6.16) translocation, suggest that differential maturation of the translocation-bearing sperm and the chromosomally normal reciprocal exists. The findings further support the concept that sperm chromosomal complement affects their maturation and function, and that factors on chromosome 6 and the X or Y chromosome additively affect sperm function. PMID- 1497889 TI - A rat sperm flagellar surface antigen that originates in the testis and is expressed on the flagellar surface during epididymal transit. AB - We identified a rat sperm flagellar surface antigen using an IgG1 monoclonal antibody (MC31) against rat epididymal sperm. Avidin-biotin-peroxidase immunohistochemistry demonstrated that the antigen was first expressed in the cytoplasm of early primary spermatocytes, then gradually became restricted to the principal piece of the sperm flagellum during spermatogenesis. However, when the sperm reached the corpus epididymidis, the antigen was expressed on the surface of both the principal piece and the midpiece of the flagellum. The epithelial cells of the epididymis were not stained with MC31. Immunogold electron microscopy showed that the antigen was present on the surface of the sperm flagellar plasma membrane. Immunoblotting of Triton X-100 extracts of epididymal sperm after one-dimensional sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) under nonreducing conditions demonstrated that MC31 detected a major antigen of 26,000-28,000 daltons (26-28K). Two-dimensional isoelectric focusing and SDS-PAGE indicated that the 26-28K antigen had an isoelectric focusing point (pl) of 5.8-5.3; minor antigens were also detected from 26K (pl 5.8) to 35K (pl 5.0). These results indicate that the antigen recognized by MC31 is an acidic 26-35K protein that originates in the testis, is integrated into the sperm flagellar plasma membrane of the principal piece during spermatogenesis, and then is expressed on the entire flagellar surface during epididymal transit. PMID- 1497890 TI - Calcium-activated potassium channels expressed from cloned complementary DNAs. AB - Calcium-activated potassium channels were expressed in Xenopus oocytes by injection of RNA transcribed in vitro from complementary DNAs derived from the slo locus of Drosophila melanogaster. Many cDNAs were found that encode closely related proteins of about 1200 aa. The predicted sequences of these proteins differ by the substitution of blocks of amino acids at five identified positions within the putative intracellular region between residues 327 and 797. Excised inside-out membrane patches showed potassium channel openings only with micromolar calcium present at the cytoplasmic side; activity increased steeply both with depolarization and with increasing calcium concentration. The single channel conductance was 126 pS with symmetrical potassium concentrations. The mean open time of the channels was clearly different for channels having different substituent blocks of amino acids. The results suggest that alternative splicing gives rise to a large family of functionally diverse, calcium-activated potassium channels. PMID- 1497891 TI - Laminar specificity of extrinsic cortical connections studied in coculture preparations. AB - The formation of specific neural connections in the cerebral cortex was studied using organotypic coculture preparations composed of subcortical and cortical regions. Morphological and electrophysiological analysis indicated that several cortical efferent and afferent connections, such as the corticothalamic, thalamocortical, corticocortical, and corticotectal connections, were established in the cocultures with essentially the same laminar specificity as that found in the adult cerebral cortex, but without specificity of sensory modality. This suggests the existence of a cell-cell recognition system between cortical or subcortical neurons and their final targets. This interaction produces lamina specific connections, but is probably insufficient for the formation of the modality-specific connections. PMID- 1497892 TI - A peptide derived from the Shaker B K+ channel produces short and long blocks of reconstituted Ca(2+)-dependent K+ channels. AB - A 20 amino acid synthetic peptide, corresponding to the amino-terminal region of the Shaker B (ShB) K+ channel and responsible for its fast inactivation, can block large conductance Ca(2+)-dependent K+ channels from rat brain and muscle. The ShB inactivation peptide produces two kinetically distinct blocking events in these channels. At lower concentrations, it produces short blocks, and at higher concentrations long-lived blocks also appear. The L7E mutant peptide produces only infrequent short blocks (no long-lived blocks) at a much higher concentration. Internal tetraethylammonium competes with the peptide for the short block, which is also relieved by K+ influx. These results suggest that the peptide induces the short block by binding within the pore of Ca(2+)-dependent K+ channels. The long block is not affected by increased K+ influx, indicating that the binding site mediating this block may be different from that involved in the short block. The short block of Ca(2+)-dependent K+ channels and the inactivation of Shaker exhibit similar characteristics with respect to blocking affinity and open pore blockade. This suggests a conserved binding region for the peptide in the pore regions of these very different classes of K+ channel. PMID- 1497893 TI - Internal blockade of a Ca(2+)-activated K+ channel by Shaker B inactivating "ball" peptide. AB - Shaker B inactivating peptide ("ball peptide", BP) interacts with Ca(2+) activated K+ (KCa) channels from the cytoplasmic side only, producing inhibition of channel activity. This effect was reversible and dose and voltage dependent (stronger at depolarized potentials). The inhibition of KCa channels by BP cannot be mimicked by an inactive point mutation of the BP, L7E. BP binds to KCa channels in a bimolecular reaction (dissociation constant of 95 microM at +40 mV). The binding site is probably located in the internal "mouth" or conduction pathway, since both external K+ and internal tetraethylammonium relieve BP induced inhibition. These results suggest that KCa channels possess a binding site for the BP with some properties similar to the ball receptor found in Shaker B K+ channels. PMID- 1497894 TI - Subcellular segregation of two A-type K+ channel proteins in rat central neurons. AB - In the mammalian nervous system, K+ channels regulate diverse aspects of neuronal function and are encoded by a large set of K+ channel genes. The roles of different K+ channel proteins could be dictated by their localization to specific subcellular domains. We report that two K+ channel polypeptides, Kv1.4 and Kv4.2, which form transient (A-type) K+ channels when expressed in Xenopus oocytes, are segregated in rat central neurons. Kv1.4 protein is targeted to axons and possibly terminals, while Kv4.2 is concentrated in dendrites and somata. This differential distribution implies distinct roles for these channel proteins in vivo. Their localizations suggest that Kv1.4 and Kv4.2 may regulate synaptic transmission via presynaptic, or postsynaptic mechanisms, respectively. PMID- 1497895 TI - Regulation of ciliary neurotrophic factor expression in myelin-related Schwann cells in vivo. AB - Adult rat sciatic nerve is known to express high levels of ciliary neurotrophic factor (CNTF) mRNA and protein. Here we examine the cellular localization of CNTF protein and mRNA in peripheral nerve and the regulation of CNTF expression by peripheral axons. In intact nerve, CNTF immunoreactivity is found predominantly in the cytoplasm of myelin-related Schwann cells. After axotomy, CNTF immunoreactivity and mRNA levels fall dramatically and do not recover unless axons regenerate. This behavior is similar to the pattern of myelin gene expression in these nerves. We conclude that the expression of CNTF in Schwann cells depends on axon-Schwann cell interactions. PMID- 1497896 TI - Opioid inhibition of GABA release from presynaptic terminals of rat hippocampal interneurons. AB - Opiates and the opioid peptide enkephalin can cause indirect excitation of principal cortical neurons by reducing inhibitory synaptic transmission mediated by GABAergic interneurons. The mechanism by which opioids mediate these effects on interneurons is unknown, but enkephalin hyperpolarizes the somatic membrane potential of a variety of neurons in the brain, including hippocampal interneurons. We now report a new, more direct mechanism for the opioid-mediated reduction in synaptic inhibition. The enkephalin analog D-Ala2-Met5 enkephalinamide (DALA) decreases the frequency of miniature, action potential independent, spontaneous GABAergic inhibitory postsynaptic currents (IPSCs) without causing a change in their amplitude. Thus, we conclude that DALA inhibits the action potential-independent release of GABA through a direct action on interneuronal synaptic terminals. In contrast, DALA reduces the amplitude of action potential-evoked, GABA-mediated IPSCs, as well as decreases their frequency. This suggests that the opioid-mediated inhibition of non-action potential-dependent GABA release reveals a mechanism that contributes to reducing action potential-evoked GABA release, thereby decreasing synaptic inhibition. PMID- 1497897 TI - Functional expression and CNS distribution of a beta-alanine-sensitive neuronal GABA transporter. AB - The synaptic action of gamma-aminobutyric acid (GABA) is terminated by high affinity, Na(+)-dependent transport processes in both neurons and glia. We have isolated a novel GABA transporter cDNA, GAT-B, which encodes a high affinity (Km = 2.3 microM), Na(+)- and Cl(-)-dependent GABA transport protein that is potently blocked by beta-alanine, a compound generally considered a selective inhibitor of glial transport. However, in situ hybridization studies indicate that GAT-B mRNA is expressed predominantly within neurons. These data indicate that the neuronal glial distinction of GABA transporters based on inhibitor sensitivities must be reconsidered and suggest a greater diversity of GABA transporters than has been predicted by previous pharmacologic studies. PMID- 1497898 TI - Two cellular inductions involved in photoreceptor determination in the Xenopus retina. AB - Cellular determination in the Xenopus retina is not a strict consequence of cell lineage or cell birthdate. This suggests that a retinal cell gets its fate by either local cellular interactions, diffusible factors, or an indeterminate stochastic mechanism. We have performed an in vitro experiment in which cellular contact is controlled to test the first possibility directly. We use these experiments to demonstrate that two cellular inductions are involved in photoreceptor determination in vitro and that these inductions also occur during development in the retina in vivo. The first interaction is responsible for biasing cells toward either a generic photoreceptor or a cone fate, while the second directs cells toward a rod cell fate. PMID- 1497899 TI - Introduction: the matrix metalloproteinase family. PMID- 1497900 TI - The matrix metalloproteinases and their inhibitors. AB - A number of metalloproteinases that degrade the extracellular matrix of connective tissues and two specific tissue inhibitors of metalloproteinases (TIMPs) have now been isolated, characterized, and cloned. Comparison of the enzyme sequences has allowed the delineation of domain structures, and initial studies have been carried out to assess the contribution of these domains to their biochemical and biologic properties, including activation, inhibition by TIMPs, and matrix binding. Such events represent the major levels of extracellular regulation of metalloproteinase activity, which is thought to be an important aspect of their control. Activation is probably a cell surface phenomenon, involving the plasminogen activator cascade or other membrane associated mechanisms. The inhibitory action of TIMPs is postulated to be as important in activation as in the subsequent regulation of enzyme degradation of the matrix. PMID- 1497901 TI - "Oh, no. Not another cytokine."--MCP-1 and respiratory disease. PMID- 1497903 TI - Modulation of fibronectin production of bovine bronchial epithelial cells by transforming growth factor-beta. AB - Regulation of airway repair after injury is poorly understood but is thought to be important in the development of airway diseases such as chronic bronchitis and asthma. There is evidence that fibronectin (Fn), an extracellular matrix glycoprotein, has a role in repair processes. In addition, transforming growth factor-beta (TGF-beta) is also likely involved in would healing and is known to influence extracellular matrix constituents in other cell systems. We postulated that TGF-beta may effect airway repair by modulating Fn production from airway epithelial cells. To examine this hypothesis, we studied the effect of TGF-beta 1 on Fn production by bovine bronchial epithelial cells in culture. Fn, released into the media of cultures exposed to TGF-beta 1, increased in a dose- and time responsive fashion. Fn in the cell layer also increased in response to TGF-beta 1. De novo protein synthesis was demonstrated by an increase in [35S]methionine incorporation into Fn immunoprecipitated from media of TGF-beta-treated cultures. TGF-beta 1 also induced an increase in expression of Fn mRNA from cultured bronchial epithelial cells, suggesting that TGF-beta modulates Fn production of these cells, at least in part, through modulation of Fn gene expression. These data support a role for TGF-beta in airway repair through modulation of Fn production by airway epithelium. PMID- 1497902 TI - Effect of acute inflammatory lung injury on the expression of monocyte chemoattractant protein-1 (MCP-1) in rat pulmonary alveolar macrophages. AB - Using a well-characterized rat model of immune complex-mediated acute inflammatory lung injury, we determined that there is a time-dependent elaboration of monocyte chemotactic activity in bronchoalveolar lavage fluid. Monocyte chemotactic activity is also significantly enhanced in culture supernatants from pulmonary alveolar macrophages (PAMs) from injured rat lungs. Northern hybridization analysis revealed markedly increased expression of rat monocyte chemoattractant protein 1 (MCP-1) mRNA in PAMs obtained from rats with immune complex-induced lung injury. The increased expression of MCP-1 mRNA and associated increase in monocyte chemotactic activity present in culture supernatants of PAMs from injured rat lungs suggest that PAMs may participate in the pathogenesis of acute inflammatory lung injury by the secretion of monocyte chemoattractants including MCP-1. PMID- 1497904 TI - Transforming growth factor-beta is generated in the course of hypersensitivity pneumonitis: contribution to collagen synthesis. AB - Mice of the C57BL/6 strain were instilled with optimal doses (150 micrograms/day for 3 days/wk) of the thermophilic actinomycete Faeni rectivirgula (also known as Saccharopolyspora rectivirgula or Micropolyspora faeni) to induce a hypersensitivity pneumonitis inflammation that mimics the human disease affecting certain occupational groups. This mouse model was characterized by a very significant alveolitis (3-fold increase in bronchoalveolar lavage [BAL] cell number at 48 h and a 10-fold increase at 3 wk). Also, total lung transforming growth factor (TGF-beta) was shown to be elevated in treated mice as early as 1 wk after the first instillation and increased gradually to 2.5 micrograms/lung at 3 wk (approximately 0.3 microgram/lung in saline-instilled controls). Intranasal instillation with F. rectivirgula was also associated with very significant increases in lung fibroblast collagen synthesis, starting at 2 wk. BAL macrophages from mice instilled with F. rectivirgula were found to release significantly more TGF-beta upon in vitro stimulation with zymosan beads than did BAL macrophages from saline-instilled mice. Finally, we show that supernatants from activated BAL macrophages of mice given F. rectivirgula increased quite significantly collagen synthesis in normal mouse lung fibroblasts. This increase could be abrogated by treating conditioned medium with a rabbit antibody against TGF-beta. Collectively, these data suggest that TGF-beta is generated in the course of experimental mouse hypersensitivity pneumonitis and contributes significantly to collagen synthesis. PMID- 1497905 TI - Characterization of the mucin differentiation in human lung adenocarcinoma cell lines. AB - Four human lung adenocarcinoma cell lines were established in serum-free F12 medium supplemented with insulin, transferrin, hydrocortisone, cholera toxin, selenium, epidermal growth factor, bovine hypothalamic extract, and retinoic acid. Histochemical analyses with periodic acid-Schiff with and without diastase treatment (PAS-D technique) and immunocytochemistry with a mucin-specific monoclonal antibody demonstrated that three of the cell lines (CL2, CL3, and NCL2) were capable of mucin production. Biochemical characterizations of mucin produced by adenocarcinoma cells were focused on one of the cell lines, CL2 cells, which showed the most prominent reactivity with mucin-specific monoclonal antibody. Biochemical analysis using the mucin precursors [3H]glucosamine and [14C]serine indicated that CL2 cells can synthesize high-molecular-weight (M(r) greater than 200 kD) glycoprotein molecules that can be immunoprecipitated by this mucin-specific monoclonal antibody. The high-molecular-weight glycoproteins isolated from CL2 cells specifically reacted with mucin-specific monoclonal antibody by Western blot analysis, and composition analyses showed high levels of serine and threonine and a low level of aromatic amino acids, which are similar to human airway mucin. These observations suggest that lung adenocarcinoma CL2 cells cultured in this serum-free medium can retain function of airway mucin synthesis. Cell kinetic studies of these four cell lines showed that the cell line (CL1) without the mucin differentiation had a higher proliferative index and a shorter population doubling time as compared with the other three cell lines (CL2, CL3, and NCL2) with mucin differentiation. Examination of the retinoblastoma protein expressions in these adenocarcinoma cell lines revealed a phosphorylated pattern that correlated inversely with the mucin synthesis status of these cell lines.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1497906 TI - Condensed tannin promotes the release of arachidonic acid from rabbit resident alveolar macrophages. AB - The condensed tannin present in cotton mill dust profoundly alters the functional capabilities of resident alveolar macrophages. Previous studies from this laboratory have shown that in vitro exposure of rabbit resident alveolar macrophages to condensed tannin significantly inhibits the ability of these cells to produce reactive oxygen intermediates or to ingest particles. In the present study, we demonstrate that condensed tannin also alters arachidonic acid (C20:4) metabolism in these cells. Exposure of rabbit resident alveolar macrophages to condensed tannin results in the time- and dose-dependent release of C20:4 from the membrane phospholipids. The release of C20:4 occurred only at tannin concentrations greater than 25 micrograms/ml and was maximal 90 min after the onset of exposure. The EC50 for release was 75 micrograms/ml. Exposure to 100 micrograms/ml tannin resulted in the release of 20 +/- 3% of the [14C]C20:4 incorporated in the cell membrane. In comparison, exposure to 160 micrograms/ml zymosan resulted in the release of 14 +/- 4% of the [14C]C20:4. For both tannin and zymosan, phosphatidylcholine and phosphatidylinositol were the principal sources of the released C20:4. Approximately 63% of the C20:4 released after zymosan stimulation was further metabolized, mainly via the cyclooxygenase pathway. The major metabolites were 6-keto-prostaglandin F1 alpha, prostaglandin F2 alpha, and prostaglandin E2. In contrast, only 24% of the C20:4 released by tannin was subsequently further metabolized. The metabolites formed were essentially evenly distributed between products of the cyclooxygenase pathway and the lipoxygenase pathway. Exposure of alveolar macrophages to 50 micrograms/ml tannin for 30 min reduced the ability of the cells to subsequently incorporate C20:4 by 50 to 70%. In contrast, exposure of the cells to 160 mg/ml zymosan for 30 min had only a minimal effect on the subsequent ability of these cells to incorporate C20:4. These results indicate that tannin promotes C20:4 release, at least in part, by inhibiting its reacylation back into phospholipids, a mechanism that differs from that of zymosan. PMID- 1497907 TI - Dexamethasone-induced increase in platelet-derived growth factor (B) mRNA in human alveolar macrophages and myelomonocytic HL60 macrophage-like cells. AB - Platelet-derived growth factor (B) (PDGF(B)) from alveolar macrophages is thought to play a central role in orchestrating the fibrotic response. Because corticosteroids are widely used in the treatment of patients with lung fibrosis, we asked whether corticosteroids modulated PDGF(B) gene activation in macrophages. PDGF(B) mRNA in alveolar macrophages obtained from smokers was increased after culture in the presence of dexamethasone (P less than 0.05), interferon-gamma (IFN-gamma) (P less than 0.05), or both in combination (P less than 0.05). Dexamethasone did not alter the abundance of mRNA encoding transforming growth factor-beta (TGF-beta), but did decrease the mRNA of early growth response gene 2 (EGR2). These initial experiments required large numbers of cells and thus were performed on macrophages from smokers. The results were reproduced when PDGF(B) mRNA abundance in macrophages from healthy nonsmoking volunteers was measured by the reverse-transcriptase polymerase chain reaction (RT-PCR). There was an increase in PDGF(B) mRNA in macrophages from nonsmokers after stimulation with dexamethasone alone (P less than 0.05) or in combination with IFN-gamma (P less than 0.05). To provide adequate cell numbers for kinetic and dose-response studies, the in vitro model of phorbol ester (TPA)-induced differentiation of HL60 cells to macrophage-like cells was used. In these cells, dexamethasone caused a 20-fold increase in the abundance of PDGF(B) mRNA, which was concentration and time dependent but not associated with changes in TGF-beta or EGR2 mRNA. This study suggests that in addition to their anti-inflammatory effects, corticosteroids may also increase the abundance of PDGF(B) mRNA. PMID- 1497909 TI - Nucleus and gene expression. PMID- 1497908 TI - Effects of inhibition and induction of cytochrome P-450 isozymes on hyperoxic lung injury in rats. AB - Pulmonary oxygen toxicity most likely results from excessive production of reactive oxygen species. The role of the cytochromes P-450 in this process is controversial because these enzymes have been reported both to enhance hyperoxic lung injury and to protect from the damaging effects of 100% oxygen. We sought to further determine the role of the cytochromes P-450 in hyperoxic lung injury by inhibiting and inducing pulmonary cytochrome P-450 isozymes in rats. Treatment with the cytochrome P-450 inhibitor cimetidine or 8-methoxypsoralen did not improve survival or reduce lung edema in rats exposed to 100% oxygen. The activity of cytochrome P-450IIB1, the major pulmonary cytochrome P-450 isozyme in rats, was clearly inhibited by 8-methoxypsoralen. beta-Naphthoflavone (beta NF), a selective inducer of cytochrome P-450IA1, was administered in two-dose and five dose regimens. The two-dose regimen produced significant and sustained induction of cytochrome P-450IA1 activity, but survival in these rats was not improved when exposed to 100% oxygen. In rats treated with five doses of beta NF, a small increase in survival time was found from 71.1 +/- 8.7 to 88.0 +/- 20.2 h; however, there was no difference in the induction of cytochrome P-450IA1 activity between this five-dose regimen and the two-dose regimen. The small improvement in survival after five doses of beta NF is thus unrelated to cytochrome P-450IA1 induction. We conclude that neither inhibition of cytochrome P-450IIB1 activity nor induction of cytochrome P-450IA1 activity protects adult rats against hyperoxic lung injury. PMID- 1497910 TI - Centromeres and telomeres. AB - Centromeres and telomeres are both composed of specific DNA sequences and unique chromosomal proteins. Isolation and characterization of some of these sequences and proteins has greatly increased our knowledge of centromere and telomere structure. This information is allowing us to determine how centromeres and telomeres perform their various roles in a cell. PMID- 1497911 TI - Cis and trans mechanisms of DNA repair. AB - DNA repair is essential for genetic stability and variability. Remarkable advances in the understanding of DNA repair by the molecular analysis of the substrate (gene repair) or the enzyme (repair genes), emphasize evolutionary conservation. Recent progress also stresses the interaction(s) between DNA repair and numerous other cellular metabolic processes, including non-nuclear and/or non genetic responses. PMID- 1497912 TI - Chromatin changes during the cell cycle. AB - Considerable progress has recently been made in elucidating the biochemical mechanisms regulating changes in chromatin structure during all stages of the cell cycle. Although anticipated, the apparently ubiquitous role played by phosphorylation/dephosphorylation reactions in modulating these changes is, nonetheless, remarkable. PMID- 1497913 TI - Nuclear envelope structure. AB - The past 18 months have seen significant advances in our knowledge of the constituents of the nuclear envelope, their interactions during interphase and the mechanisms involved in their mitotic dynamics. Although most of the new data are in general agreement with, and contribute detail to, our traditional image of the nuclear envelope, a few observations appear to mark the beginning of new and important directions in research. PMID- 1497914 TI - Chromatin structure and gene expression. PMID- 1497915 TI - RNA processing. AB - Significant progress has been made over the last year in our understanding of the roles that RNA-binding proteins play in pre-mRNA splicing, the components of the spliceosome and how these components relate to the mechanism of splicing. Of particular importance has been the sequence analysis of the first mammalian splicing factors and structural determination of an RNA-binding domain. PMID- 1497916 TI - An acquired state: epigenetic mechanisms in transcription. AB - Even when we know the primary sequences and binding specificities of every transcriptional activator and repressor, our understanding of transcriptional regulation will be rudimentary. This is partly because major aspects of gene expression are governed by epigenetic mechanisms. These mechanisms may be responsible for apparently identical sequences being read by the transcriptional machinery in two different but heritable ways: active or repressed. Epigenetic transcriptional states have been encountered in a number of recent experiments. PMID- 1497917 TI - Transcription factors and the control of DNA replication. AB - Initiation of DNA replication is mediated by the assembly of nucleoprotein complexes at cis-acting DNA sequences known as origins of replication. Recent studies in several systems show that accessory transcription factors accentuate origin utilization by multiple mechanisms. The remarkable similarities in the activities of accessory transcription factors at promoters and origins of replication suggest that transcription factors play a pivotal role in the regulation of chromosomal DNA synthesis in eukaryotic organisms. PMID- 1497918 TI - Myc and Max: a putative transcriptional complex in search of a cellular target. AB - Biochemical and genetic observations have supported the hypothesis that Myc family proteins function to regulate genes important in cellular growth and differentiation. The recent findings that Myc proteins can associate with other cellular proteins, possess sequence-specific DNA-binding activity and may directly transactivate transcription of several candidate genes have provided an experimental framework in which to test the transcription factor model. Based on principles established for several well characterized viral oncoproteins, a model is presented in which the regulation of Myc function is controlled by specific cellular protein interactions that serve to activate or repress transactivation activity or deny access of the Myc complex to its target sequences. PMID- 1497919 TI - New twists in class III transcription. AB - Recent work emphasizes the similarity between polymerase II and III in the mechanisms of transcription. Highlights of the past year include the alignment of individual polypeptides within class III transcription complexes and the demonstration that class III transcription machinery includes TFIID and an RNA component. PMID- 1497920 TI - Transcription factors: positive and negative regulators of cell growth and disease. AB - Recent advances in our understanding of transcription factors that regulate RNA polymerase II transcribed genes are described. This review considers the role of alternate protein-protein interactions to yield positive or negative regulation, the consequences of deregulated factor activity on cell function and approaches to establish factor-binding specificities. PMID- 1497921 TI - Advances in RNA polymerase II transcription. AB - Multiple protein factors are necessary to mediate transcription by RNA polymerase II. Recently, a number of advances have been made in our understanding of how general transcription factors collectively modulate basal transcription in the context of different promoter environments and how this process is activated and repressed by accessory components. PMID- 1497923 TI - Nucleus and gene expression. PMID- 1497922 TI - Signal transduction: the nuclear target. AB - Fos and jun heterodimers activate the transcription of genes containing an AP-1 site. The activity of Fos and Jun proteins is regulated by post-translational modification. The activity of the rel/NF-kappa family of transcriptional factors is regulated by their sequestration in the cytoplasm in association with the inhibitor protein, I kappa B. An ankyrin repeat motif in I kappa B proteins is required for their direct association with rel/NF-kappa B. PMID- 1497924 TI - Strut fracture with Bjork-Shiley 70 degrees convexo-concave valve. An international multi-institutional follow-up study. AB - Between 1980 and 1983, 831 Bjork-Shiley 70 degrees convexo-concave prosthetic heart valves were implanted at five institutions in Sweden, Germany. The Netherlands, and Canada. As of January 1991, there were 34 outlet strut fractures occurring from 0.2 to 10.1 years (median = 4.6 years) after implantation. In addition, there were 28 sudden, unexplained deaths. The mortality after strut fracture was 84%. The mortality after emergency valve replacement for strut fracture was 50%. The 10-year actuarial fracture rate (standard error) was 10.5 (2.4)% for large (29-33 mm) valves vs. 3.3 (1.2)% for 21-27 mm valves (P less than 0.001). Within valve size groups, fracture rates for aortic and mitral valves were similar. Cox regression analysis found only valve size to be significantly associated with strut fracture. There is a further subgrouping of the valves according to the manufacturer: group I are the earlier large 29-33 mm) valves; group II are the later large valves; group III are the small size (21-27 mm) valves. The risk of strut fracture was highest in group I (12.3% at 10 years) with an approximatively constant hazard (1.4% per year). A comparison was made with a statistical model incorporating all cases reported to the manufacturer. This model estimates fracture rates approximately 63%-73% of those found in the present study. These findings lead us to recommend that group I patients should be considered for elective reoperation on an individual basis, giving careful attention to risk factors and contraindications. PMID- 1497925 TI - An appraisal of patch enlargement of the small aortic annulus in 33 patients undergoing aortic valve replacement. AB - To avoid the problem of valve prosthesis/patient mismatch in the late postoperative period, we have adopted patch enlargement of the small aortic annulus in 33 patients having undergone aortic valve replacement since 1975, when the aortic annulus could not accept a large enough prosthesis. The mean age was 40 years, including 2 children aged 4. The technique of patch enlargement utilized was Nicks' method wherein the incision does not extend onto the mitral leaflet. In 31 adult patients, the aortic annulus before enlargement ranged in diameter from 18 to 24 mm with an average of 20.8 mm. After enlargement, the diameter of the annulus was 25.0 mm on average. In 2 children, the mean diameter of the annulus was enlarged from 16.5 mm to 20.5 mm. There were 2 early deaths in the initial series and 2 late deaths. Patch enlargement of the small aortic annulus is a simple, safe, and effective adjunct permitting the insertion of a valve one or two sizes larger than that which could be accommodated by the native annulus. PMID- 1497926 TI - The hydrodynamic function and leaflet dynamics of aortic and pulmonary roots and valves: an in vitro study. AB - Fresh homograft aortic and pulmonary roots were tested in a pulsatile flow simulator to assess their hydrodynamic function and leaflet opening characteristics. Simultaneous flow and pressure measurements were obtained for a range of cardiac outputs. The effective orifice area and regurgitant volumes were calculated. The mean pressure difference across the pulmonary roots was obtained under both left and right side pressures. A video recording of valve leaflet function was also obtained for each valve. A comparison was made with four porcine bioprosthetic heart valves (21 and 23 mm). The mean pressure difference with respect to flow for the 21 mm Hancock II and Intact porcine bioprostheses was significantly higher than that for all aortic roots tested. The 24 mm aortic root showed significantly lower pressure drop compared to all porcine valves tested. The mean pressure difference across each pulmonary root at pulmonary pressures was significantly greater than at systemic pressures. At systemic pressures the fully open leaflets had a triangular orifice with low leaflet open bending strains at the commissures. At the lower internal pressures, with reduced dilation of the root, higher bending strains were noted. These were not as severe as seen in porcine valves. PMID- 1497927 TI - Plication of the diaphragm for unilateral eventration or paralysis. AB - Unilateral diaphragmatic paralysis and eventration have the same appearance and provoke the same disturbances. Diaphragmatic plication is intended to decrease lung compression, to make the thoracic base and mediastinum more stable, and to strengthen the respiratory action of intercostal, perithoracic, and abdominal muscles: 13 infants and children were operated upon, 7 in acute respiratory failure and ventilator-dependent, 4 in chronic respiratory failure; 11 adults were operated upon, 8 with respiratory and 3 with digestive symptoms. Four infants who had been operated upon before the 10th day of life died: 3 from associated diseases and 1 from a lung infection. The 9 survivors have been followed up for a mean period of 6.6 years. All were asymptomatic and the position of the plicated diaphragm was maintained. The 11 adults have been followed up for a mean period of 8.5 years. Nine were asymptomatic; in 1, dyspnea had decreased; in 1, reflux persisted and was surgically cured. In 5 adults, the respiratory tests showed a mean amelioration of 20% of vital capacity and 15% of forced expiratory volume in 1 s. In infants, the prognosis depends on associated malformations and on the condition of the lung. Plication should be performed after 2 weeks on a ventilator. In older children and adults, plication is justified when the anomaly produces symptoms (malignancy excluded). Plication is simple, efficient, and durable, but there is no indication of subsequent diaphragmatic function: its effects on respiratory mechanics are probably indirect. PMID- 1497928 TI - Mediastinoscopy vs. anterior mediastinotomy in the diagnosis of mediastinal lymphoma: a randomized trial. AB - We selected 95 patients with mediastinal adenopathy and no signs of goiter, myasthenia gravis or mediastinal involvement by other disease. All patients underwent, for screening purposes, transthoracic fine needle aspiration biopsy based on chest x-ray and CT findings. Patients were then subdivided into 4 groups. One group of 22 patients with prevalent anterior mass localization underwent anterior mediastinotomy. One group of 19 patients with prevalent middle mediastinal mass localization underwent cervical mediastinoscopy. Two other groups of 27 patients each with both anterior and middle mediastinum localization randomly underwent anterior mediastinotomy or mediastinoscopy. Fifty-one Hodgkin's and 44 non-Hodgkin's lymphomas were diagnosed in total. In 11 cases (11.57%), median sternotomy (2) or thoracotomy (9) were necessary for establishing the final diagnosis. The overall diagnostic accuracy was 80.43% for cervical mediastinoscopy and 95.91% for anterior mediastinotomy. The statistical analysis performed on all patients showed a significant difference (chi 2 = 5.56, P less than 0.025, df = 1) between the two procedures. PMID- 1497929 TI - Intermediate to late results of surgical relief of vascular tracheobronchial compression. AB - Since 1979, a total of 69 infants and children aged 0.1 to 11.9 (median 0.7) years required surgical intervention for: double aortic arch (26), anomalous origin of innominate artery (26), right aortic arch with left ligamentum arteriosum (9), pulmonary artery sling (5), retroesophageal right subclavian artery (3). Before operation, the morbidity was high: 84% of children were symptomatic in the first trimester of life with 24 patients requiring mechanical ventilation. Seven children had an accompanying heart defect. Left thoracotomy was the preferred approach. There were 2 early (asphyxic brain damage, postoperative pneumonia) and 2 late (tracheomalacia, complex heart defect) deaths. Five patients (2 originally operated elsewhere) needed reoperation for persistent symptoms. All 65 survivors are well 1 month to 11.9 (mean 3.9 +/- 3.62) years after surgery. Tracheobronchoscopy, magnetic resonance imaging, and lung function testing were helpful for postoperative evaluation. Minor tracheal compression was revealed in 4 patients despite their good clinical condition. PMID- 1497930 TI - Myocardial oxygen consumption and lactate production during antegrade warm blood cardioplegia. AB - Continuous warm blood cardioplegia has recently been recommended as an alternative to multidose cold blood cardioplegia for myocardial protection during coronary bypass operations. Cardioplegia may have to be interrupted in order to provide a bloodless operating field during coronary anastomosis. To determine the effects of ischemia at normothermia on myocardial oxygen consumption and lactate production we randomized 17 dogs to receive either warm blood cardioplegia (37 degrees C) or cold blood cardioplegia combined with systemic and topical cooling. After initiating arrest, cardioplegia was interrupted for periods of 1, 2, 3, 4, 5, 6, and 10 min. Myocardial oxygen debt occurred after 3.5 min of ischemia in the 9 animals receiving warm blood cardioplegia. In contrast, myocardial oxygen consumption never exceeded oxygen availability during cold blood cardioplegia (P less than 0.001). Lactate production increased linearly in both groups but was much greater in those animals receiving warm blood cardioplegia (P less than 0.001). Spontaneous electromechanical activity was much more common during warm blood cardioplegia which required frequent infusions of cardioplegia to maintain cardiac arrest (P less than 0.0003). CONCLUSIONS: (1) Oxygen debt occurred after 3.5 min of warm ischemia; (2) spontaneous electromechanical activity is more common during warm heart protection which necessitates the use of larger volumes of cardioplegia to maintain cardiac arrest. PMID- 1497932 TI - Total cavopulmonary connection for right ventricular endomyocardial fibrosis. AB - Endomyocardial fibrosis is an endemic problem in tropical countries and is characterised by ventricular cavity obliteration, decreased ventricular compliance, and atrioventricular valve regurgitation. We report on a patient with right ventricular endomyocardial fibrosis resulting in obliteration of the cavity and tricuspid regurgitation treated successfully by total cavopulmonary connection and exclusion of the right ventricle. PMID- 1497931 TI - Evaluation of myocardial protection by combination of lidoflazine pretreatment and St. Thomas' Hospital cardioplegia in aorto-coronary bypass grafting. AB - The concept of pretreatment of the myocardium with a pharmacological agent protecting the cell against ischemic and reperfusion injury is very attractive. Lidoflazine, a calcium overload blocker, predominantly membrane stabilizing, is able to prevent cell damage during ischemic arrest and reperfusion. The purpose of this study was to determine whether the combination of lidoflazine pretreatment and St. Thomas' Hospital cardioplegia can provide, in clinical practice, better myocardial protection in aorto-coronary bypass grafting than St. Thomas' Hospital cardioplegia alone. As indices for myocardial protection, recovery of cardiac function, enzyme release, and clinical outcome were registered. Ninety-three patients undergoing aorto-coronary bypass surgery were studied. These patients were randomized into two groups in a double blind fashion. Patients in group A (n = 48) received lidoflazine 1 mg/kg intravenously over a period of 20 min before initiation of cardiopulmonary bypass. Group B (n = 45) receiving placebo, acted as a control group. Myocardial protection consisted of intermittent infusion of cold 4 degrees C St. Thomas' Hospital cardioplegia, topical slush ice, and systemic hypothermia (28 degrees C rectal). No significant differences between the two groups were noted in terms of recovery of cardiac function, enzyme release, incidence of myocardial infarction, low cardiac output, rhythm, and conduction disturbances. In conclusion, our data suggest that the combination of intravenous pretreatment with lidoflazine and St. Thomas' Hospital cardioplegia did not provide significant additional myocardial protection in the clinical situation. PMID- 1497933 TI - Ventriculo-pulmonary fistula. PMID- 1497934 TI - Implantable cardioverter defibrillators (ICD): successful implantation using a single endocardial lead. PMID- 1497935 TI - Doppler color imaging. Introduction. PMID- 1497936 TI - Evaluation of peripheral venous disease. AB - DCI is an excellent method for evaluation of the venous system and has several distinct advantages over other methods. One of the major benefits of DCI, particularly with the addition of capabilities to image slow-flow characteristics of veins, is the ease and rapidity of evaluating the lower extremity veins, including not only the femoral and popliteal system but also the major calf veins. The identification of nonoccluding intraluminal thrombus is enhanced by the additional contrast provided by color-flow imaging. In a similar fashion, flow imaging by scanning through the urine-filled bladder permits excellent visualization of the external iliac veins, and in thin patients the common iliac veins and distal inferior vena cava can be assessed. Thus, DCI permits a more rapid examination with increased diagnostic confidence; it may also permit a more accurate examination. The noninvasive and complication-free nature of the examination recommends it strongly as the primary test, particularly in patients with contraindications to contrast evaluation. PMID- 1497937 TI - Doppler color imaging. Abdomen. AB - Abdominal applications of Doppler ultrasonography are becoming increasingly important as familiarity with Doppler principles and instruments grows. The availability of sensitive duplex and DCI instruments specifically adapted for use in the abdomen and pelvis has stimulated interest in the use of Doppler techniques as a complement to conventional imaging. Although the simultaneous display of tissue and flow information has enhanced the ease of evaluation of vascular abnormalities and increased diagnostic confidence, the role of Doppler is only just beginning to be defined. Since blood flow is a fundamental factor in health and disease, it is hoped that the new information provided by Doppler evaluation of the abdomen will continue to advance the role of ultrasound as a primary diagnostic method as Doppler and color imaging technology mature. PMID- 1497938 TI - Doppler color imaging. Obstetric and gynecologic applications. AB - The addition of pulsed and color Doppler has greatly added to the diagnostic potential for obstetric and gynecologic ultrasound. In addition to improved morphologic detail inherent in the use of EVUS, new information is available on perfusion and the physiologic changes associated with the menstrual cycle and early pregnancy. The absence of luteal flow strongly predicts unsuccessful pregnancy outcome in patients undergoing therapy for infertility. This introduces the possibility of more economic use of expensive treatments. Later in pregnancy, DCI aids in the efficient and accurate performance of Doppler spectral sampling and contributes to the evaluation of structural and functional abnormalities of the fetus, umbilical cord, and placenta. Applications in the evaluation of patients with suspected ectopic pregnancy, incomplete abortion, and pseudosac are welcome additions for clinical problems that currently result in many malpractice suits. Finally, the recognition of neovascular flow, especially in the ovary, raises hope for improved and earlier diagnosis of ovarian cancer. PMID- 1497939 TI - Doppler color imaging. Scrotum, breast, thyroid, and extremities. AB - DCI, when coupled with small-parts gray-scale imaging, has demonstrated great utility in the evaluation of superficial body abnormalities. This technique has rapidly become a primary method of evaluation of suspected testicular torsion, and its results are competitive with those of standard nuclear medicine examinations. DCI evaluation of male impotence, coupled with intracavernous injection of vasoactive substances, is now a leading, noninvasive technique for diagnosis of both arteriogenic and venogenic causes. DCI may provide invaluable information in the evaluation of palpable masses, particularly in the diagnosis of vascular abnormalities such as false aneurysm and arteriovenous fistula. Further studies are needed to corroborate the utility of DCI in the evaluation of focal thyroid and parathyroid abnormalities, breast carcinoma, nodal cancer, and the orbit. Because this technique is applicable to superficial, high-frequency examinations, DCI is rapidly becoming an accepted and frequently necessary part of any small-parts ultrasound study. PMID- 1497940 TI - Doppler color imaging. Intraoperative and cranial applications. AB - In infants normal intracranial vessels may be seen in detail by using DCI. This capability is most useful in the initial or follow-up examination of infants with intracerebral AVMs. Aside from this, few clinically important applications of DCI to image the intracranial vessels have been reported. PMID- 1497941 TI - Doppler color imaging. Carotid and vertebral arteries. AB - Duplex sonography and DCI have now become standard modalities for imaging of the extracranial carotid and vertebral arteries. They are equivalent in accuracy to arteriography in the evaluation of flow-limiting stenosis. In addition, the newest scanners all appear to have high-resolution imaging systems capable of characterizing plaque properly. DCI currently leads to more rapid scanning and greater ease in evaluating more difficult patients. The most important advance with DCI will come in the future, when there is better understanding of the significance of the Doppler color-flow patterns now being observed. At present, duplex sonography and DCI remain the only imaging modalities that can evaluate the complete spectrum of abnormalities of the extracranial carotid and vertebral vessels, from minimal stenosis to complete occlusion. As a result, they are valuable tools in the diagnosis of disease. PMID- 1497942 TI - Doppler color imaging. Principles and instrumentation. AB - DCI acquires Doppler-shifted echoes from a cross-section of tissue scanned by an ultrasound beam. These echoes are then presented in color and superimposed on the gray-scale anatomic image of non-Doppler-shifted echoes received during the scan. The flow echoes are assigned colors according to the color map chosen. Usually red, yellow, or white indicates positive Doppler shifts (approaching flow) and blue, cyan, or white indicates negative shifts (receding flow). Green is added to indicate variance (disturbed or turbulent flow). Several pulses (the number is called the ensemble length) are needed to generate a color scan line. Linear, convex, phased, and annular arrays are used to acquire the gray-scale and color flow information. Doppler color-flow instruments are pulsed-Doppler instruments and are subject to the same limitations, such as Doppler angle dependence and aliasing, as other Doppler instruments. Color controls include gain, TGC, map selection, variance on/off, persistence, ensemble length, color/gray priority. Nyquist limit (PRF), baseline shift, wall filter, and color window angle, location, and size. Doppler color-flow instruments generally have output intensities intermediate between those of gray-scale imaging and pulsed-Doppler duplex instruments. Although there is no known risk with the use of color-flow instruments, prudent practice dictates that they be used for medical indications and with the minimum exposure time and instrument output required to obtain the needed diagnostic information. PMID- 1497943 TI - Ultra-high-resolution scanning electron microscopic studies on the sarcoplasmic reticulum and mitochondria of the rat intrafusal muscle fibers. Part II: The extracapsular region. AB - The three-dimensional structure of the transverse-axial tubular system, sarcoplasmic reticulum (SR) and mitochondria in the extracapsular region of the intrafusal muscle fibers of the rat lumbrical muscle was observed by ultra-high resolution scanning electron microscopy after removal of the cytoplasmic matrix by the osmium-DMSO-osmium procedure. Nuclear chain fibers possessed thick to moderately sized column-forming mitochondria with occasional I-band branches. The transverse tubules (T-tubules) running at the level of the A-band side of the A-I junction were sandwiched between two large terminal cisternae for most of their length, forming triads. The sarcotubules arising from the terminal cisternae formed single-layered networks at the A-band level, and well developed, double layered, three-dimensional networks at the I-band level. Nuclear bag1 fibers possessed slender column-forming mitochondria devoid of I-band branches. The T tubules were located at the level of the A-I junction. Both the T- and the axial tubules were occasionally coupled with small terminal cisternae, forming dyads or triads. At the I-band level, the SR was well developed and formed single layered networks, but at the A-band level only a few longitudinally arranged sarcotubules and axial tubules were observed. Nuclear bag2 fibers contained medium to large diameter column-forming mitochondria without I-band branches. The T-tubules ran at the level of the A-band adjacent to the A-I junction, and were coupled at some intervals with terminal cisternae of various lengths. Swollen, large terminal cisternae were frequently seen.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1497944 TI - Alveolar bone remodeling in the early stage of experimental apical periodontitis in the rat mandible. AB - Apical periodontitis was surgically induced in the mandibular first molar of rats and chronological changes in the periapical bone tissue were observed by histochemistry and electron microscopy. On the second postoperative day (Day 2), tartrateresistant acid phosphatase (TRACPase)-positive cells emerged on the bone surface facing the inferior alveolar nerve, whereas alkaline phosphatase (ALPase) positive cells proliferated on the bone marrow surface of the mandibular canal wall. On Day 3, the active resorption of the mandibular canal wall appeared on the surface facing the inferior alveolar nerve. The bone of the upper wall of the canal was completely resorbed. On Day 4, however, numerous ALPase-positive cells emerged over the bone surface facing the inferior alveolar nerve intermingled with TRACPase-positive cells. On Day 5, repair of the upper wall of the mandibular canal by new bone progressed. Bone formation was also observed on the bone surface facing the inferior alveolar nerve. On Day 6, the upper wall of the mandibular canal was remodeled by the new bone, whereas TRACPase-positive cells had already migrated over the bone surface in the vicinity of ALPase-positive cells. From Days 2 to 5, active trabecular bone formation continued in the bone marrow cavity close to the mandibular canal, while TRACPase-positive cells were found only on Day 6. These demonstrate that inflammatory stimuli activate bone formation coupled with bone resorption, as well as direct trabecular bone formation without a bone resorption phase. A rapid bone turnover in the early stage of apical periodontitis is also suggested. We conclude that bone defects in apical periodontitis are not the result of sole bone resorption but rather, active bone remodeling. PMID- 1497945 TI - Light and electron microscopic immunocytochemistry of TSH-like cells occurring in the pars tuberalis of the adult male rat pituitary. AB - Morphological characteristics of TSH-immunoreactive cells (TSH-like cells) in the pars tuberalis (PT) of intact adult male rats were studied by light and electron microscopic immunocytochemistry. TSH-like cells in the rat PT can be classified into three types by light microscopy: 1) cells diffusely stained throughout the cytoplasm, 2) diffusely weak stained cells containing a strongly stained spot in the paranuclear region; 3) cells with a strongly stained spot in the paranuclear region without diffuse reaction. We call the latter two cell types "spot cells". Electron microscopic immunocytochemistry revealed that the latter two cells reacted very strongly in the Golgi apparatus. The spot cells were localized throughout the PT from rostral to caudal extremities as well as the ventral surface area of the pars distalis (PD) which was connected to the PT. The cytoplasm of the TSH-cells in the PD proper was strongly and diffusely stained with anti-TSH serum, while there was no spot-like staining in any cells. The spot cells demonstrated by electron microscopy contained a well developed Golgi apparatus, many microvesicles and a few secretory granules. These immunocytochemical results clearly showed two apparently distinct types of TSH immunoreactive cells between the PT and PD in the intact adult male rat adenohypophysis. This morphological distinction of TSH-immunoreactive cells suggests functional differences in these cells. PMID- 1497946 TI - Ultrastructure of the water-clear cell in the rabbit parathyroid gland. AB - The ultrastructure of water-clear cells has been described in human hyperplastic parathyroid glands. However, previous studies have failed to demonstrate this type of cell in normal human or other vertebrate parathyroid glands. Upon recently recognizing water-clear cells in the parathyroid glands of the golden hamster, we intended to examine the occurrence of these cells in other animals. In the present study the parathyroid glands of about one-year-old rabbits were observed by electron microscopy. Water-clear cells containing numerous vacuoles were demonstrated dispersed among the chief cells. The cells were generally situated close to the basal lamina of perivascular space which lay against the capillary vessel and were attached by desmosomes to the chief cells. Irregularly shaped vacuoles in the water-clear cells resembled dilated cisternae of the granular endoplasmic reticulum in the chief cells. Several ribosomes could be seen attached to the membrane of some of the irregularly shaped vacuoles. It is conceivable that the water-clear cells are transformed from the chief cells. PMID- 1497947 TI - A light and electron microscopic study on pulpal nerve fibers in the lower incisor of the mouse. AB - Light and electron microscopic studies were made on pulpal nerve fibers in mouse lower incisors, typical continuously growing teeth. Serial sections, from the apex of the odontogenic sheath to the incisal edge of the apical foramen, were examined by light microscopy to identify myelinated fibers passing through the apical foramen. The fine structure of the pulpal nerves was examined by electron microscopy at three sites: 1) the level at the incisal edge of the apical foramen; 2) a level 5 mm incisal from the apex of the odontogenic sheath; and 3) the level where the incisor comes out of the alveolar bone. No myelinated fibers were found passing through the apical foramen; they were also lacking at the three levels of the pulp. At level 2, unmyelinated axons were seen in close contact with smooth muscle fibers of arterioles. At level 3, nerve fibers were difficult to distinguish from processes of fibroblasts and odontoblasts. Degenerating axons were present in Schwann cells, and fine unmyelinated axons running through the odontoblast cell layer were seen. Various types of unmyelinated axons were observed in the apical region (level 1). These axons were classified into 6 types on the basis of their fine structures: Type I, bundles of unmyelinated axons completely or partly ensheathed by Schwann cell cytoplasm (mature type); Type II, bundles of unmyelinated axons in a space formed by a Schwann cell membrane (regenerating type); Type III, bundles of unmyelinated axons ensheathed not by a Schwann cell, but merely by a basal lamina (regenerating type); Type IV, single axons in direct contact with the basal lamina (regenerating or terminal type); Type V, naked, electron-dense axons with many vesicles and mitochondria (growth cone-like type); and Type VI, electron opaque axons, due to loss of axonal organellae (degenerating type). The significance of these structures is discussed in relation to the continuous growth of the rodent incisor. PMID- 1497948 TI - Ultrastructural and immunocytochemical studies of enamel tufts in human permanent teeth. AB - Enamel tufts were exposed after decalcification of the enamel matrix and their fine structures and immunocytochemical characteristics were examined. Under the binocular microscope and the scanning electron microscope (SEM), enamel tufts appeared as corrugated ribbon-like structures located on the dentine parallel to the tooth axis. SEM observation disclosed enamel tufts as bundles of well extended tubular structures with cross striations attributable to hypocalcified enamel sheaths. Plate-like structures were observed at the center of enamel tufts, where they ran parallel to the enamel tufts. Under the transmission electron microscope (TEM), the plates of tufts revealed their origin in the superficial layer of the dentine, penetrating the hypercalcified zone adjacent to the dentine-enamel (D-E) junction, and then reaching the tuft region. The plates of tufts ran mainly along the enamel sheaths and partially across the prisms in the tuft region. THe protein-A-gold technique revealed an intense immunoreactivity for amelogenin over the superficial layer of the dentine, but over the enamel prisms in the tufts nor over the plates of tufts. The immunoreactivity for 13-17 kd protein was detected over the filamentous structures closely associated with the enamel sheaths in the enamel tuft. Thus our study disclosed that enamel tufts consist of both well extended hypocalcified enamel prisms and plates of tufts. The major organic component of the enamel tufts is suggested to be 13-17 kd protein rather than amelogenin. PMID- 1497949 TI - Changes in subcellular structures of parietal cells in the rat gastric gland after omeprazole. AB - Omeprazole, an inhibitor of gastric acid secretion, was administered to rats at a dosage of 20 mg/kg/day for 14 and 35 days, and subsequent changes in subcellular structures of parietal cells were analyzed using morphometry and immunocytochemistry. Plasma gastrin levels were also examined, showing two times higher levels in the experimental groups than in the non-treated control. The volume and surface densities significantly decreased in tubulovesicles of the cells in the experimental rats. In the long term treatment of omeprazole (35 days), the volume density of microvilli on the membranes of secretory canaliculi in the cells also decreased significantly, whereas that of lysosomes clearly increased. By electron microscopy, many dense bodies of various shapes often appeared in the cytoplasm of parietal cells after the omeprazole treatment. Immunocytochemistry revealed that large granular immunodeposits for cathepsin B increase in the epithelial cells of the gastric glands after omeprazole treatment. These results suggest that omeprazole induces quantitatively significant decreases in both tubulovesicles and canalicular microvilli. The decreases in these membrane structures may possibly be ascribed to the degradation of the membrane in lysosomes; the proton pump on the membranes bound irreversibly with omeprazole is believed destined to be degraded in lysosomes. PMID- 1497950 TI - Histochemical and immunohistochemical demonstration of macrophages and dendritic cells in the lingual periodontal ligament of rat incisors. AB - The distribution of macrophages in the lingual periodontal ligament of rat incisors was surveyed by histochemical and immunohistochemical methods. Numerous macrophages showing intense ACPase reactions were located primarily in the shear zone of the periodontal ligament. Immunostaining with an ED1-monoclonal antibody that recognizes various subpopulations of macrophages revealed plentiful positive cells showing flamelike profiles throughout the periodontal ligament, in addition to regular macrophages associated with sinusoidal blood vessels. A similar distribution of flamelike cells expressing Ia antigens was demonstrable with immunostaining using an OX6-monoclonal antibody. A consecutive staining of sections for ACPase histochemistry followed by immunoreactions for Ia antigens revealed the presence of two types of the flamelike cells in the periodontal ligament: one with and the other without distinct ACPase activity, corresponding to the macrophage and the dendritic cell, respectively. Either type of flamelike cells was located in the bone-related and shear zones, whereas only dendritic cells without ACPase activity were restricted to the tooth-related zone. OX6 immunonegative cells showing ACPase reactions were also found in the periphery of the sinusoidal blood vessels. Our data are the first to demonstrate the abundance of macrophages and dendritic cells expressing Ia antigens throughout the lingual periodontal ligament of rat incisors. In addition to regular macrophages, an exclusive localization of macrophages with flamelike extensions has been demonstrated in the bone-related and shear zones of the ligament. The region specific arrangement of macrophages and dendritic cells with various histochemical and immunological features suggests that the periodontal ligament of rat incisor is a useful model for analyzing the process of differentiation of antigen-presenting cells. PMID- 1497952 TI - Why do intelligent children have learning difficulties? The neuropsychological perspective. PMID- 1497951 TI - Recent advances in the management of chronic renal failure in childhood. PMID- 1497953 TI - Health problems and service use by parents of normal infants in the first 6 months of life. AB - A retrospective descriptive study was carried out on residents of the northern Sydney health area who delivered normal, full term, singleton infants at three large maternity units. A sample population of 1199 was sent a postal questionnaire when their infants reached the age of 6 months, and a 65% response rate was obtained. Problems encountered, with ratings of severity and difficulty of management, were reported in five categories: acute and persistent or recurrent illness, daytime and night-time behaviour problems and feeding problems. Forty-seven per cent of parents reported at least one problem which they rated severe or very difficult to manage, and 19.7% reported two or more, particularly in the areas of behaviour and feeding difficulties. Traditional services such as those provided by general practitioners and specialists were not often helpful for these problems, while baby health services and specialized support services were more helpful. However, a significant number of respondents found no service helpful, representing an area of unmet need. PMID- 1497954 TI - Pathogenesis of Duchenne muscular dystrophy: the calcium hypothesis revisited. AB - Rapid advances in the molecular genetics of Duchenne muscular dystrophy (DMD) and the discovery and localization of the gene product dystrophin has brought new hope that successful treatment for this disease may not be too far away. Dystrophin has been postulated to have a mechanical function, helping to resist stress associated with muscle contraction. The presence of dystrophin in low concentrations in muscle cells, its expression in nervous tissue and the observation that hypercontraction of the sarcomeres precedes membrane rupture make the hypothesis unlikely. On the basis of an analogy with a cytoskeletal protein ankyrin, which is associated with the sodium/potassium adenosine triphosphatase (ATPase) in the kidney, it is possible that dystrophin deficiency leads initially to an increased but inefficient calcium-ATPase activity, which pumps calcium out of the cell. Partial failure of the pump would result in intracellular accumulation of calcium, hypercontractions of the sarcomeres, rupture of the cell membrane, massive influx of calcium and cell necrosis. PMID- 1497955 TI - Parental perception of the effect of venepuncture in preschool children in non therapeutic research. AB - Non-therapeutic research in children is said to be justified in part if the risk involved is no more than minimal, but there is little information on the risk of venepuncture to make that judgement. This prospective study was carried out to assess the effect of venepuncture on 425 healthy children aged between 3.6 and 6.6 years old who participated in a non-therapeutic research project. A parental questionnaire was sent out 1 month after the blood was taken. Three hundred and ninety-one parents (92%) returned the questionnaires. Parental responses indicated the risk of complications was of the order considered to be minimal. A large majority of parents (78%) felt this experience would be helpful for the child if blood had to be taken again and a significant proportion (40%) felt the child would be more confident when going to see a doctor or dentist afterwards. Venepuncture in preschool children causes minimal harm and might even have some positive effects. PMID- 1497956 TI - A review of chest physiotherapy in neonatal intensive care units in Australia. AB - Clinical techniques and protocols for chest physiotherapy vary greatly from one Neonatal Intensive Care Unit to another. In 1988 a questionnaire designed to investigate differing techniques used was distributed to Neonatal Intensive Care Units (NICU) around Australia. Fourteen of the 15 questionnaires were completed and returned. The results revealed that the methods of chest treatment and the indicators for commencing chest treatment were similar throughout NICU. Both physiotherapists and nursing staff played a role in the performance of chest treatment in all but one unit where it was the responsibility of nursing staff. However, the area in which there was most variability between NICU was the individual treatment protocols employed pre- and postextubation of the neonate. A review of literature over the past 10 years also demonstrates variability in chest physiotherapy. It was concluded that further well-controlled studies with larger sample sizes are needed to validate the use of chest physiotherapy for the neonate, especially in relation to the techniques and specific protocols employed. PMID- 1497957 TI - Chronic lung disease in very low birthweight infants: a prospective population based study. AB - A prospective population-based study of chronic lung disease among all very low birthweight infants (birthweight 500-1499 g) born in New Zealand in 1986 is reported. Of 413 of these infants admitted to neonatal units, 355 (86%) survived to 28 days. An additional 50 infants were recorded as liveborn but died in the labour ward or other place of birth. Both observed survival and survival adjusted for birthweight, gestation and gender were significantly (P less than 0.05) better in larger centres. Oxygen requirement was assessed at 28 days of age, 36 weeks equivalent gestation and 84 days of age, when 38.6, 23.1 and 13.8% of infants, respectively, were being treated with oxygen. To examine the joint effects of predictor variables on oxygen requirement at each age, the data were analysed using multiple logistic regression methods. At 28 days, lower birthweight, shorter gestation, respiratory distress syndrome (all P less than 0.0001), and gender and hospital principally caring for the infant (both P less than 0.05) were significantly associated with treatment with oxygen. In comparison with other studies, New Zealand appears to have a relatively high rate of chronic lung disease. We speculate that a contributing factor may be the small size of some regional neonatal units. PMID- 1497958 TI - Alcohol burns in the neonate. AB - The case histories of two infants who sustained chemical burns due to contact with alcoholic skin preparation solutions are presented. The skin permeability of the extremely low birthweight infant renders them susceptible to major burns following relatively brief exposure to such solutions. Care is needed in the selection and use of skin disinfection solutions in the neonatal nursery. PMID- 1497959 TI - Drug errors in intensive care. AB - Errors in prescription, administration, delivery and interaction of drugs are likely in children in intensive care units because of the large number of often unfamiliar medications these children receive. We evaluated prospectively the frequency and consequence of drug errors in a large multidisciplinary intensive care unit. There was a mistake in drug prescription, administration, delivery or drug interaction in 2% of medication orders, with 12% of these mistakes causing actual harm to the patient. The frequency of drug errors must be appreciated and due care must be taken in checking and delivering drugs to children in an intensive care unit. PMID- 1497960 TI - An evaluation of three methods used to assess the gestational age of aboriginal neonates. AB - Many Aboriginal women do not recall their last menstrual period date, so alternative methods of estimating gestational age are necessary for optimal obstetric and neonatal care. In this retrospective review of 605 Aboriginal infants born at the Royal Darwin Hospital, the gestational age was estimated by the Dubowitz method and compared with available gestational age estimates from first fundal height and first ultrasound measurement. There was good agreement between the Dubowitz and ultrasound estimates of gestational age with best agreement occurring when ultrasound was done in the first trimester and worst agreement in the third trimester. Agreement between fundal height and Dubowitz estimates was poor but the measurement of fundal height was not standardized. When accurate last menstrual period information is absent, these findings suggest that good estimates of gestational age in Aboriginal neonates can be determined from the Dubowitz assessment at birth and from ultrasound measurements taken in the first trimester. PMID- 1497961 TI - Outcome of infants with birthweight 2000 g or less who undergo major cardiac surgery. AB - A retrospective study of all neonates with birthweight 2000 g or less undergoing major cardiac surgery at the Royal Children's Hospital, Melbourne over the last 5 years was performed in order to determine outcome and identify subgroups within this population that may have a poor prognosis. The mean length of stay in intensive care following surgery was 32 days, with non-survivors having a significantly longer duration of stay than survivors. Overall mortality was 43%, and for children with congenital heart disease as part of a recognizable syndrome the mortality was 100%. None of the survivors suffered incapacitating cardiac, neurological or respiratory handicap. These children in general have a poor prognosis and utilize significant resources; results of cardiac surgery in this group need to be closely followed in the future. PMID- 1497962 TI - The prehospital management of children with acute asthma. AB - Parents of 100 children admitted sequentially to hospital with acute asthma were interviewed in order to determine the frequency of the use of asthma action plans and the intensity of prehospital treatment. The results revealed that 51% of the parents possessed some form of action plan and 84% of this group used their plan prior to the child's admission to hospital. However 79% of those children with more than two prior hospital admissions for asthma had an action plan. Bronchodilator therapy was widely used, with widespread possession of nebulizer units, but tended to be given infrequently prior to hospital admission. Steroid use in the acute attack was inadequate. Despite a concurrent national asthma campaign prehospital management was considered to be suboptimal. PMID- 1497963 TI - Partial sacral agenesis with constipation: a report of one family. AB - Seven first degree relatives in three generations of a family with partial sacral agenesis are reported. Anterior sacral meningoceles were found in five cases, four of whom had severe constipation, one with urinary voiding dysfunction, and another without constipation who had low pressure headaches and dyspareunia. The anomalad was transmitted in an autosomal dominant fashion with incomplete penetrance and variable expression. This entity should be considered in all children and adults with severe constipation from birth, a family history of constipation and/or where constipation is refractory to medical therapy. PMID- 1497964 TI - Failure of allogeneic bone marrow transplantation to benefit HIV infection. AB - A 16 year old boy underwent allogeneic bone marrow transplantation (BMT) from an human leukocyte antigen (HLA)-identical sibling for severe aplastic anaemia. He was symptomatic for 7 years before transplantation and had received multiple red blood cell and platelet transfusions. Conditioning for BMT consisted of cyclophosphamide, antilymphocyte globulin and total lymphoid irradiation. Engraftment was rapid, there was no evidence of rejection despite the history of multiple blood product transfusions and he did not develop acute or chronic graft versus host disease. He was well for the first 8 months after transplantation but then developed fevers, interstitial pneumonia, herpes simplex infections and cytomegalovirus enteritis. Serological studies revealed antibodies to human immunodeficiency virus (HIV) and he was considered to have acquired immune deficiency syndrome (AIDS). Retrospective analysis of the serum samples showed that he was seronegative for HIV until approximately 10 months before transplantation when his serum became HIV positive. Lymphocyte function studies done after transplantation suggested immunologic recovery at 3 months post transplant with a brisk though subnormal response to phytohaemagglutinin stimulation. T cell subset analysis performed subsequently showed complete absence of CD4 positive cells indicating immune incompetence which was associated with clinical features of AIDS. Bone marrow transplantation had failed to produce sustained immunologic reconstitution and prevent the progression of HIV to which he ultimately succumbed. PMID- 1497965 TI - Homozygous pyruvate kinase deficiency in Hong Kong ethnic minorities. AB - Three cases of pyruvate kinase (PK) deficiency resulting in congenital haemolytic anaemia with transfusion dependency are described. These cases resulted from consanguineous marriages in non-Han Chinese and include a pair of twins. We believe this to be the first documentation of homozygous PK deficiency in the Hong Kong population. The diagnosis was masked due to transfusion dependency in each case stressing the need to take a sample of pretransfusion blood for PK enzyme assay, and for family studies, when this disorder is suspected. PMID- 1497966 TI - Tubercular stricture of the duodenum in a child. PMID- 1497967 TI - [Long-term results of talus fractures]. AB - In a retrospective study we analysed 29 operative treated fractures of the Talus. The classification of Marti and Weber has been used in this study. The incidence of necrosis was 17% of the group III and IV and that one of arthritis 27%. There was no infection in our series. We doubt that a longterm non weight-bearing with a caliper brace has an effect on the outcome of a necrosis of the Talus. The evidence of the Hawkins' sign on the ap-radiograph at 6-8 weeks is a good and simple parameter of the vitality of the Talus. PMID- 1497968 TI - [Prevention of medical occupational accidents]. AB - Technical measures are not sufficient to prevent occupational accidents in patients with specific diseases. Since 1984 the Swiss National Accident Insurance Fund (SUVA) has the possibility to clarify the working conditions and medical aspects of patients presumed to suffer a special risk to occupational accidents. The actual situation and the experiences in the medical prevention of occupational accidents in Switzerland since 1984 are described. PMID- 1497969 TI - [Therapy refractory accident patients and post-traumatic stress disorder]. AB - The appearance of post-traumatic stress disorder (PTSD) is presented and discussed. Three case reports of patients concerned by an accident demonstrate, that not diagnosed PTSD may be the reason of the lack of response to rehabilitation interventions. PMID- 1497970 TI - [Surgical treatment of radial head fracture]. AB - Fractures of the radial head are often combined with ligament ruptures or subluxations creating instability of the elbow joint. Cartilage avulsions of the capitellum trapped between the fragments are a frequent observation. We advocate ORIF for displaced fractures. The posterolateral approach avoiding compression of the radial nerve may be prolonged proximally with an osteotomy of the humeral epicondyle giving full overview of the circumference of the head. It allows the harvesting of cancellous bone used as a graft to fill in articular depressed areas or metaphyseal defects. The stabilisation is achieved with thin screws of 1.5 mm diameter introduced in different planes, their head slightly sunken in the cartilage. Lately miniplates have been used in cases of neck fractures with surprisingly good functional results. The author reports about the results in 42 of 49 operated patients. PMID- 1497971 TI - [The medical and insurance technical part of expert assessment]. AB - The expert's demands careful exploration including consideration of psychological factors. Furthermore, to establish their final reports the insurance companies involved need detailed answers to specific questions in regard to the impairment. The medical expert finds himself in an area of conflict between doctor-patient relationship (which requires mutual trust) and his duty as an expert. His task will be made easier if he clearly separates the first part of his report dealing with the medical aspects from the second part referring to the more technical problems of the insurer. It is only after clarification of the medical situation that the questions relating to the insurance as such can be clearly answered. Factors which do not seem to relate directly to the medical aspects of the accidental sequels (e.g. psychosomatic), but which the Swiss Insurance Court does take more and more into account, may be mentioned, however, their evaluation is best left to the insurance company which ordered the expert's report. PMID- 1497972 TI - [Movement therapy group for psychiatric patients]. PMID- 1497973 TI - [Meals. The elderly, nutrition and life style--results from a study in Baerum]. PMID- 1497974 TI - [Help after personal injury--how do you cope with it?]. PMID- 1497975 TI - [Offshore nurse: a harsh and independent job. Offshore health services]. PMID- 1497976 TI - [Offshore Nurse. Historical development and field of responsibility]. PMID- 1497977 TI - [Offshore health services: special groups and projects]. PMID- 1497978 TI - [A foray into history. Developments in health--from ancient times to our own time]. PMID- 1497979 TI - [Walkers in the maternity department]. PMID- 1497980 TI - [Pain clinics in Aker. Nurses' role in pain clinics]. PMID- 1497981 TI - [Drug handling. Standard routines in institutions]. PMID- 1497982 TI - [Community health services. Who manages health services in the community?]. PMID- 1497983 TI - [Groups as methods in psychiatric nursing education]. PMID- 1497984 TI - [Psychiatry--talk more with patients than about them!]. PMID- 1497986 TI - [Health visitor has bad conscience. Interview by Kjell Arne Bakke]. PMID- 1497985 TI - [Close contact ends in marriage. Interview by Kjell Arne Bakke]. PMID- 1497987 TI - [Teach elderly ladies to be tough. Interview by Siv Barstad]. PMID- 1497988 TI - [His entire life on the neonatal unit]. PMID- 1497989 TI - [Admission to the gynecological ward]. PMID- 1497990 TI - [New meeting with Ceaucescus' stepchildren]. PMID- 1497991 TI - [Milk is not healthy for everyone]. PMID- 1497992 TI - [Nurses and medication errors]. PMID- 1497993 TI - [Minister of Social Affairs: hospitals will continue!. Interview by Kjell Arne Bakke]. PMID- 1497994 TI - [Leave health priority setting to the tribunals]. PMID- 1497995 TI - [Ulleval with Scandinavia's largest maternity hospital?]. PMID- 1497996 TI - [Grief is not psychiatry. Interview by Siv Barstad]. PMID- 1497997 TI - The catalytic power of pyruvate decarboxylase. A stochastic model for the molecular evolution of enzymes. AB - Pyruvate decarboxylase (PDC) catalyzes the decarboxylation of pyruvate anion by a factor of around 10(12), compared with the non-enzymic decarboxylation by thiamine, under standard state conditions of 1 mM pyruvate and thiamine diphosphate (TDP), pH 6.2. Free-energy diagrams constructed on the basis of earlier measurements for the enzymic and non-enzymic reactions give some information on catalysis by PDC. PDC stabilizes the reactant state preceding TDP addition to pyruvate by 76 kJ mol-1 and the transition state for the addition by 83 kJ mol-1. PDC stabilizes the reactant state preceding decarboxylation (presumably alpha-lactyl-TDP) by 27 kJ mol-1 and the transition state for decarboxylation by 68 kJ mol-1. In addition, the free-energy diagrams reveal a leveling of reactant-state free energies in the enzymic reaction compared with the non-enzymic reaction, in that the former are nearly equal to each other. The enzyme-bound transition-state energies are similarly leveled. The energetic leveling of reactant states has been noted by Albery, Knowles and their coworkers in many enzymic reactions and termed 'matched internal thermodynamics.' They showed that the result would arise naturally (and inevitably) in the 'evolution to perfection' of enzymes, when the evolutionary process was treated by a deterministic model. The critical assumption of this model was the validity of a Marcus-type or Bronsted-type linear free-energy relationship between rate and equilibrium constants for reactions occurring wholly within enzyme complexes. Here a completely stochastic simulation of molecular evolution, with no deterministic assumptions, is shown to reproduce both 'matched internal thermodynamics' and the 'matched internal kinetics' or leveling of transition state energies noted here. The Albery-Knowles result is thus more general than might have been supposed. PMID- 1497998 TI - The glomerular filterability of polyfructosan-S in immature infants. AB - Gel chromatography was performed on 21 plasma, 5 urine and 3 spinal fluid samples from pre-term infants who had received intravenous polyfructosan-S (PF-S), in order to investigate whether all sizes of PF-S molecule are filtered at the glomerulus and penetrate deep extra-cellular fluid compartments. Plasma obtained after 24 h continuous infusion of PF-S had identical chromatograms to the aqueous solution, suggesting no glomerular hold-up of the largest molecules. PF-S had a broader chromatogram than inulin, suggesting that it has larger molecules. Urine and plasma samples obtained early after a single injection had an excess of high molecular weight polyfructoside, suggesting that small molecules penetrate deep extracellular fluid compartments more easily. Spinal fluid samples had an excess of low molecular weight polyfructoside, suggesting slow penetration of the largest molecules. PMID- 1498000 TI - What is the appropriate workup for a child with isolated hematuria? PMID- 1497999 TI - A reappraisal of the measurement of glomerular filtration rate in pre-term infants. AB - Thirty-seven single-injection polyfructosan-S (PF-S, Inutest) and 98 continuous infusion PF-S/creatinine clearance studies were performed in 39 sick very low birth weight infants. The single-injection clearance method for measuring glomerular filtration rate has been shown to be a reliable technique if sampling is continued for 8 h or more and the PF-S (Inutest) assay is sensitive, accurate and precise. The continuous-infusion clearance method is also valid if the infusion is continued for more than 24 h and preceded by a loading dose in the form of a double-rate infusion for 8 h. Creatinine clearance is usually less than PF-S clearance, the mean ratio being 0.91, suggesting that there is some creatinine reabsorption in the renal tubule in sick very low birth weight infants. PMID- 1498001 TI - Renal function following kidney transplantation in children treated with cyclosporine. AB - The study was performed to evaluate the long-term renal function of children treated with cyclosporine after kidney transplantation. Renal function was determined with clearances of inulin and aminohippurate sodium for evaluating glomerular filtration rate (GFR) and effective renal plasma flow (ERPF). Thirty six children aged 0.4-16.2 (median 6.9) years at transplantation were examined within 5 months of transplantation and then yearly over 0.3-7.1 years. Twenty five children and young adults, 1.5-20 (median 7.7) years of age, with solitary kidneys because of renal agenesis or nephrectomy, served as controls. The GFR and ERPF within 1 year of transplantation were significantly lower than those of controls (65 +/- 19 and 345 +/- 88 vs 96 +/- 12 and 474 +/- 91 ml/min per 1.73 m2, respectively). GFR remained constant 4 years after transplantation, but ERPF decreased significantly. Significant inverse correlations were found between GFR within 5 months of transplantation and the mean cyclosporine concentration and the number of rejection episodes. The frequency of hypertension decreased from 82% within 5 months of transplantation to 0% after 4 years. The absolute GFR increased during follow-up. In conclusion, kidney transplantation results in a reduced renal function compared with that of solitary native kidneys. The reduction in renal function correlated with the number of rejection episodes and the cyclosporine load. The increase in absolute GFR during follow-up suggests a remaining capacity for growth and/or compensatory hypertrophy. PMID- 1498002 TI - Does breast feeding protect against urinary tract infection in the first few months of life? PMID- 1498003 TI - Amelioration of hypertension and insulin resistance by 1,25 dihydroxycholecalciferol in hemodialysis patients. AB - The effects of i.v. 1,25-dihydroxycholecalciferol (DHCC) on blood pressure and insulin sensitivity were studied in 7 patients on maintenance hemodialysis and compared with 7 healthy controls. Three days after discontinuing oral 1,25-DHCC, the dialysis patients were evaluated by glucose clamp studies to quantitate insulin sensitivity, with (+D) and without (-D) a prior single dose of i.v. 1,25 DHCC at 2 micrograms/m2. Blood pressure was measured just before the glucose studies. During -D studies, the patients were hypertensive (mean arterial blood pressure 108 +/- 2 mmHg, controls 84 +/- 4 mmHg, P less than 0.02) and insulin resistant (insulin sensitivity index 7.5 +/- 0.4 mg/kg.min per microU per ml, controls 14.2 +/- 0.7, P less than 0.01). i.v. 1,25-DHCC significantly reduced the mean arterial blood pressure (96 +/- 3 mmHg, P less than 0.05) and increased insulin sensitivity (10.9 +/- 0.5 mg/kg.min per microU per ml, P less than 0.02) in the dialysis patients. I.V. 1,25-DHCC did not change blood pressure and insulin sensitivity in the control subjects. During -D studies, serum concentrations of 1,25-DHCC were significantly lower in patients than controls (P less than 0.02). Serum 1,25-DHCC during the +D studies increased to supraphysiological levels in both patients and controls. Serum concentrations of intact parathyroid hormone, total and ionized calcium, magnesium, potassium, urea nitrogen and creatinine were not different between the +D and -D studies in either the dialysis patients or the controls. These results suggest that pharmacological doses of 1,25-DHCC may have therapeutic value in the treatment of hypertension and insulin resistance in dialysis patients. PMID- 1498004 TI - Mathematical modelling of haemodialysis in children. AB - The single-pool urea kinetic model (UKM), utilising "Kt/V" (the normalised whole body urea clearance), is widely used to help assess the adequacy of haemodialysis in adults. In the presence of an adequate dietary protein intake, a value of unity is acceptable for thrice weekly dialysis. Children could benefit from this approach but, with their relatively higher protein intakes and dialysis needs, this model may not be applicable. Urea kinetics, studies in six children with chronic renal failure by serial timed blood urea measurements during and after haemodialysis, were compared with the kinetics of a one-pool and a two-pool UKM. The two-pool UKM with intra- and extracellular pools best fitted the observed data, re-equilibration between pools accounting for the marked rebound increase in blood urea seen in the 1st h after dialysis (mu 17%, SD 5). Kt/V calculated using the end-dialysis blood urea was higher (mu 21%, SD 5) than when the more correct equilibrated value was used. The post-dialysis rebound indicates significant disequilibrium between the two pools at the end of dialysis. Dialysis efficiency may be substantially overestimated unless this is allowed for by using the rebounded post-dialysis blood urea when calculating Kt/V. PMID- 1498005 TI - Cerebral oedema in congenital nephrotic syndrome. AB - We report an infant with congenital nephrotic syndrome who showed clinical and radiological evidence of cerebral oedema, which resolved during prolonged intravenous albumin therapy. The cerebral oedema in this case can possibly be attributed to the relative immaturity of the blood-brain barrier in early infancy. PMID- 1498006 TI - Acquired hyperoxaluria and haematuria in children. AB - Two children with extensive ileal resection are reported. They developed gross haematuria of "non-glomerular origin", without stones or nephrocalcinosis. Previous reports indicate that acquired hyperoxaluria is common in children with a variety of intestinal disorders. Our patients had hyperoxaluria. We think that hyperoxaluria may be the cause of haematuria through a pathogenetic mechanism similar to the one ascribed to haematuria secondary to hypercalciuria and hyperuricosuria. PMID- 1498007 TI - Aluminum toxicity in childhood. AB - Aluminum intoxication is an iatrogenic disease caused by the use of aluminum compounds for phosphate binding and by the contamination of parenteral fluids. Although organ aluminum deposition was noted as early as 1880 and toxicity was documented in the 1960s, the inability to accurately measure serum and tissue aluminum prevented delineation of its toxic effects until the 1970s. Aluminum toxicity has now been conclusively shown to cause encephalopathy, metabolic bone disease, and microcytic anemia. PMID- 1498009 TI - Ureteropelvic junction obstruction in childhood. PMID- 1498008 TI - Renal effects of growth hormone. I. Renal function and kidney growth. AB - Growth hormone (GH) affects renal function and kidney growth. Pituitary-derived or recombinant human GH (rhGH), acting via insulin-like growth factor-1 (IGF-1), increases glomerular filtration rate (GFR) and renal plasma flow (RPF) in GH deficient as well as in normal adults. Furthermore, GFR and RPF are low in hypopituitarism and elevated in acromegaly. These effects of GH on GFR and RPF have not been demonstrated in moderate renal insufficiency. IGF-1 is implicated in compensatory renal hypertrophy. Markedly elevated levels of serum GH accelerate glomerular sclerosis in rodents, although the significance of these findings for GH treatment in humans is uncertain. rhGH therapy offers great promise to children with short stature from various aetiologies. Preliminary reports on the use of rhGH in children with renal disease and after renal transplantation have not shown any consistent change in kidney function, although follow-up times are short. The long-term impact of rhGH therapy on kidney function in short children needs further evaluation. PMID- 1498010 TI - Clinical quiz. Renal tubular ectasia with congenital hepatic fibrosis. PMID- 1498011 TI - Psychosocial adjustment to end-stage renal failure. PMID- 1498012 TI - Sebaceous gland lipids. AB - Human sebum contains squalene, wax esters, triglycerides, cholesterol esters, and possibly free cholesterol. The fatty acids of the ester lipids include species with chain branching or with unusual double-bond positions. The alcohol moieties of the wax esters contain unusual chain types similar to those of the fatty acids. Genetic and hormonal factors cause individual differences in sebaceous lipid composition. Genetic factors seem to influence the proportions of the various types of branched-chain fatty acids. Androgenic stimulation of the glands causes an increase in lipid synthesis, and therefore in the ratio of endogenously synthesized lipid to exogenous lipid. Because the endogenously synthesized lipids tend to be different from lipids that are derived exogenously, the overall composition of the secretion changes. Differences in sebum composition are particularly evident when the sebum of prepubertal children is compared with that of young adults. One difference that may be of clinical significance is the different concentrations of linoleate. Higher concentrations of sebum linoleate may protect young children from comedonal acne by preventing an essential fatty acid deficiency from developing in the follicular epithelium. PMID- 1498013 TI - Epidermal lipids. AB - Epidermal lipids play important roles in cell structure, in control of growth and differentiation, in determining cohesion and desquamation, and in formation and function of a permeability barrier. Knowledge of the structures and composition of the epidermal lipids is important for understanding these functions. The lipids present in epidermis include phospholipids, monohexosylceramides, ceramides, cholesterol, cholesterol esters, cholesterol sulfate, triglycerides, and fatty acids. The phospholipids are major structural components of the plasma membranes and membranous organelles in the viable and differentiating keratinocytes. In addition, phospholipids serve in several transmembranal signaling processes and as a reservoir for arachidonic acid, the precursor of the eicosanoids. Monohexosylceramides are thought to function in the assembly of lamellar bodies, and in the final stage of differentiation are converted to a structurally heterogenous mixture of ceramides in the intercellular space of the stratum corneum and to a unique ceramide covalently attached to the corneocyte surface. The mixture of lipids in the stratum corneum, composed principally of ceramides, cholesterol, cholesterol esters, and fatty acids, prevents desiccation and limits the penetration of a variety of noxious environmental agents. The stratum corneum lipids represent a major product of epidermal differentiation, and free sphingosine liberated from ceramides in this terminally differentiated compartment may provide a feedback mechanism for the regulation of the differentiation process. PMID- 1498014 TI - Prostaglandins, leukotrienes, and hydroxy fatty acids in epidermis. AB - The skin is an organ that displays a highly active metabolism of polyunsaturated fatty acids (PUFA). Deficiency of the 18 carbon (n-6) dietary PUFA (linoleic acid) in epidermis results in scaly dermatoses and disruption of the skin barrier system. The skin possesses the enzyme systems to metabolize and interconvert a variety of lipids. For instance, it metabolizes arachidonic acid (an n-6 PUFA) via the cyclooxygenase pathway into cyclic products, predominantly prostaglandin E2 and prostaglandin F2 alpha. These prostaglandins modulate normal physiological processes at low physiological concentrations. However, at high concentrations, such as result from UV irradiation, they elicit inflammatory reactions. The skin can also metabolize 18-carbon and 20-carbon PUFA (n-6) via the 12- and 15 lipoxygenase pathways to produce predominantly monohydroxy fatty acids: 13 hydroxyoctadecadienoic acid (13-HODE), 12-hydroxyeicosatetraenoic acid (12-HETE), 15-hydroxyeicosatetraenoic acid (15-HETrE), and 15-hydroxyeicosatetraenoic acid (15-HETE). The latter two have potent anti-inflammatory properties. Therefore, it seems possible that elevation of these HETEs in vivo via dietary or topical means could suppress the cutaneous inflammatory reactions elicited by excessive generation of prostaglandins and leukotrienes. Thus, the supplementation of diets with appropriate purified vegetable oil and/or fish oil may serve as a less toxic monotherapy or as an adjunct to standard regimens in the management of skin inflammatory disorders. PMID- 1498015 TI - Structures formed by epidermal lipids in vitro. AB - The extracellular membranous structures of stratum corneum constitute the major barrier to percutaneous penetration. These intercellular lipid lamellae are devoid of phospholipids and are unique in their lipid composition. In this article, some of the recent investigations of the structures formed by the stratum corneum lipids in vitro are discussed with relevance to the barrier function of epidermis. These studies have provided some insight into the dramatic physical changes that occur in the membranous structures of the epidermis during the formation of the stratum corneum. PMID- 1498016 TI - Physical methods for studying stratum corneum lipids. AB - The skin's barrier to water loss and drug transport is closely related to the biophysical properties of the stratum corneum lipids. A number of in vitro and in vivo methods have been used to evaluate the physical properties of stratum corneum lipids. Two particularly useful techniques, infrared spectroscopy and differential scanning calorimetry, have provided a wealth of information about stratum corneum structure and function. The results of these studies demonstrate that the alteration of stratum corneum lipid packing results in increased skin permeability. Furthermore, the magnitude of increased permeability can be predicted from these physical properties. Therefore, these results provide both insight into the mechanism of transport through the stratum corneum, as well as a useful paradigm for selection of agents that reversibly alter the permeability of the skin. PMID- 1498017 TI - Epidermal lipids and topical drug delivery. AB - When a topical formulation is placed on the skin, the active drug is usually required to penetrate through the stratum corneum into the viable tissue. The major control to this process is the slow diffusion through the dead horny layer. The major route of drug penetration through the stratum corneum is via the tortuous intercellular channels. It is therefore important to ascertain the nature of the environment that the drug experiences within the intercellular pathway and how it is affected by the presence of formulation components. The lipids within the intercellular channels are a complex mixture but they are structured into bilayer arrays. Extraction of the lipids by solvents within the formulation will lead to enhanced permeability of the skin. Some penetration enhancers act by creating disorder in the alkyl chains of the lipid bilayers; others modify the solubility characteristics within the stratum corneum. The different interactions that are possible will be discussed in this article. PMID- 1498018 TI - Model studies of epidermal permeability. AB - An in vitro physical model approach for describing and predicting transport of molecules and ions across skin is examined. The proposed model is represented by two transport-resistant layers in series: the stratum corneum and the epidermis plus dermis. The stratum corneum is regarded as the principal barrier to transport and is composed of two parallel pathways: the lipoidal pathway and the pore pathway. The epidermis-dermis is treated as a porous membrane. The model predicts three regimes for the transport behavior of permeants, and these predictions have been compared with experimental permeability coefficient data obtained with hairless mouse skin in a two-chamber (aqueous) diffusion cell. The model predicts (1) that extremely lipophilic molecules are rate-limited by the epidermis-dermis and have a limiting permeability coefficient value; (2) that extremely polar permeants are rate-limited by the pore pathway of the stratum corneum with its limiting permeability coefficient; and (3) that permeants with intermediate polarity are transported via the lipoidal pathway and exhibit a lipophilicity-dependent permeability coefficient. Experimental data involving a large number of permeants are found to be consistent with these model predictions. The model approach also has been applied in the study of the mechanism(s) of skin transport enhancement induced by short-chain alkanols in aqueous media. A possible mode of enhancing the lipoidal pathway at low concentrations of the alkanols may involve the polar head region of the lipid bilayer or the region slightly below the polar head plane, or both; alkanols may solvate the lipid-water interface, intercalating and disrupting the interactions of the upper regions of the alkyl chains and the interactions between the polar head groups. This could result in an increase in both diffusivity and partitioning tendency for a permeant in this microenvironment. At higher alkanol concentrations, the pore pathway becomes dominant in controlling the transport of the permeants across the stratum corneum. PMID- 1498019 TI - Studies of epidermal lipids using electron microscopy. AB - Ruthenium tetroxide fixation has permitted the electron microscopic visualization of intercellular lipid lamellae in thin sections of stratum corneum. This development complements prior freeze-fracture studies of lipid lamellae and has advanced our knowledge about the ultrastructure of epidermal lipids in several ways. We have demonstrated a continuous lipid envelope that surrounds each differentiated stratum corneum cell and the presence of lipid lamellae throughout the entire stratum corneum of three mammalian species, including humans. Wherever lamellae are seen, they are present in multiples of one, two, or more pairs of bilayers, consistent with their formation from fused, flattened lipid vesicles. A unique pattern of lipid monolayers intervening between each pair of bilayers, based on sharing lipid chains between bilayers, has been proposed. In regions where there are no intercellular lamellae between corneocytes, intervening monolayers are in contact with adjacent lipid envelopes that might be involved in stratum corneum cohesion. However, limitations to the ruthenium technique must be overcome before changes in lamellar patterns can be accurately attributed to, or correlated with, changes in permeability brought about by experimental procedures or in diseased states. PMID- 1498020 TI - In vivo studies of cutaneous lipid biosynthesis. AB - The epidermis and the sebaceous glands are both characterized as terminally differentiating tissues in which cells produced by replication in the germinative layer progress during several weeks through a programmed series of biochemical and morphological changes that end in cell death and eventual sloughing of the final metabolic products. Because of these slow changes and the presence of successive anabolic and catabolic regimes in the same tissue, classic methods of biochemistry using cell homogenates have not been widely successful. Much of what is known of the lipid metabolic pathways has therefore been obtained from experiments with biopsy materials or in intact animals. Radiotracer experiments in intact animals have been successful largely because the lipid products into which the radiolabel is incorporated are not lost to the general circulation during the several weeks in which they are retained in the tissue. Nor are they subject to continual degradation and resynthesis that would be the case in most other tissues, but progress steadily through the series of biochemical transformations that occur along with the morphologic changes characteristic of the epidermal and sebaceous tissues. Furthermore, of the radiolabel that enters the general circulation, only an insignificant proportion returns to the cutaneous tissues to obscure the local metabolic activities. PMID- 1498021 TI - Epidermal lipids and scaling diseases of the skin. AB - Alterations in epidermal lipid content or metabolism underlie several scaling diseases of the skin in man and experimental animals. The importance of cholesterol to epidermal homeostasis and normal desquamation is demonstrated by the scaling disorder produced by topical applications of lovastatin in experimental animals, and by the imbalance of the cholesterol sulfate:cholesterol ratio in stratum corneum in patients with recessive X-linked ichthyosis. The essential fatty acid-deficient rodent illustrates the importance of linoleic acid to epidermal function. Finally, a defect in lamellar body organellogenesis may underlie harlequin ichthyosis. PMID- 1498022 TI - Lipids and the epidermal water barrier: metabolism, regulation, and pathophysiology. AB - In addition to well-known changes in protein composition, epidermal differentiation is associated with dramatic changes in lipid content. A decrease in phospholipids and triglycerides is accompanied by enrichment in ceramides, cholesterol, and free fatty acids in the stratum corneum. The epidermis demonstrates exceptionally high basal levels of lipid synthesis, and regulates its synthetic activity in response to barrier requirements. Not all epidermal lipids are synthesized in parallel; whereas cholesterol and fatty acids are synthesized immediately after barrier disruption, sphingolipids begin to be synthesized later in the course of barrier homeostasis. In addition, with specific inhibitors of the key regulatory enzymes--3-hydroxy-3-methyl-glutaryl coenzyme A reductase (for cholesterol) and serine palmitoyl transferase (for sphingolipids)--it has been possible to demonstrate conclusively a role for these species in the barrier. Furthermore, barrier function not only regulates lipid synthesis, but also epidermal DNA synthesis, perhaps thereby providing an additional pool of lipid biosynthetic factories. These findings have considerable implications for the pathophysiology of skin diseases associated with abnormal barrier function, such as psoriasis and irritant contact dermatitis. PMID- 1498023 TI - Skin lipids. PMID- 1498024 TI - Global programme on AIDS. HIV sentinel surveillance. PMID- 1498025 TI - Expanded programme on immunization. Vaccine efficacy in a measles immunization programme. PMID- 1498026 TI - Global programme on AIDS. Unexplained severe immunosuppression in adults without evidence of HIV infection. PMID- 1498027 TI - Seroepidemiology of measles, mumps and rubella. PMID- 1498028 TI - Hydatid disease. 1988-1990. PMID- 1498029 TI - [Problems of intensive care in children with oncologic diseases]. PMID- 1498030 TI - [Surfactant substitution in respiratory distress syndrome. Nursing necessities for the care of a premature with respiratory distress syndrome after surfactant substitution]. PMID- 1498031 TI - [Reasonable and environmentally protective disinfection and hygieneic measures in pediatrics]. PMID- 1498032 TI - [Early health educational aids for children with spina bifida and their parents]. PMID- 1498033 TI - [Part-time employment in nursing without fixed time contract]. PMID- 1498034 TI - [Hans Ewerbeck (1919-1987)]. PMID- 1498035 TI - [Appendicitis in children]. PMID- 1498036 TI - [Obligation to supervise children with behavior disorders]. PMID- 1498037 TI - [Poisonous and less poisonous plants. 2]. PMID- 1498038 TI - [Baby massage]. PMID- 1498039 TI - Disorganization is a completely dominant gain-of-function mouse mutation causing sporadic developmental defects. AB - Disorganization (Ds) is an exceptional mutation because of its diverse and profound developmental effects. Although other mouse mutations produce similar congenital defects, extreme pleiotropism, random occurrence, developmental independence of multiple defects, and type of anomaly make Ds unique. Examples of developmental defects include cranioschisis, rachischisis, thoracoschisis, exencephaly, hamartomas, and anomalies of appendages, digestive, genital and urinary tracts, sense organs, limbs and girdles, tail and pharynx. No other mutation in the mouse has such broad effects. Ds is therefore an important model for studying not only the genetic control of lineage determination and pattern formation, but also the occurrence of sporadic congenital defects. To characterize the effects of gene dosage, we examined the viability and phenotype of Ds homozygotes and the phenotype of +/+/Ds trisomic fetuses. Occurrence of homozygotes was tested by intercrossing Ds/+ heterozygotes, typing genetic markers that flank Ds, and examining homozygotes for morphological abnormalities. Not only were Ds homozygotes found in their expected frequency, homozygotes were not more severely affected than heterozygotes. Trisomies provide a direct test for determining whether Ds is a gain-of-function mutation. Trisomic fetuses were derived by crossing Ds/Ds homozygous mice to hybrid mice that were heterozygous for two related Robertsonian translocations. Two trisomic fetuses had developmental defects characteristic of Ds mice. Together these results demonstrate that Ds is a completely dominant, gain-of-function mutation. PMID- 1498040 TI - Suboptimal 5' and 3' splice sites regulate alternative splicing of Drosophila melanogaster myosin heavy chain transcripts in vitro. AB - Using a Drosophila cell-free system, we have analyzed the regulation of alternative splicing of Drosophila muscle myosin heavy chain (MHC) transcripts. Splicing of MHC 3' end transcripts results in exclusion of adult-specific alternative exon 18, as is observed in embryonic and larval muscle in vivo. Mutations that strengthen either the 5' or the 3' splice sites of exon 18 do not promote inclusion of this exon. However, strengthening both splice junctions results in efficient removal of both introns and completely inhibits skip splicing. Our data suggest that the affinity of exons 17 and 19, as well as failure of constitutive splicing factors to recognize exon 18 splice sites, causes the exclusion of exon 18 in wild-type transcripts processed in vitro. PMID- 1498041 TI - Impaired T cell functions during amphibian metamorphosis: IL-2 receptor expression and endogenous ligand production. AB - T cell functions are impaired during defined developmental stages of amphibian metamorphosis (Marx et al., 1987). Here we show, using a fluorescent anti-human IL-2 receptor antibody and flow cytometry, that during these stages, the splenocytes of Xenopus laevis, the South African clawed toad, have a progressively diminished capacity to express IL-2 receptors (IL-2R), after in vitro lectin stimulation. Preincubation with human rIL-2 specifically blocks binding of the anti-IL-2R antibody. Separation of an endogenous ligand bound to the IL-2R leads to a substantial increase in available epitope recognized by the anti-IL-2R antibody when pre- and postmetamorphic splenocytes are employed, but not when splenocytes of the prometamorphic stages are treated similarly. Thus, the cells from the prometamorphic stages are not producing significant quantities of the ligand. Finally, we demonstrate that human rIL-2 is not by itself mitogenic in the toad, but it can act as a co-stimulator of antigen-induced mitogenesis. Thus, an absence of an endogenous ligand (autologous IL-2?), coupled with a reduced capacity to express IL-2 receptors may be responsible for impaired T cell clonal expansion in metamorphosing Xenopus. Inhibition of T cell functions during this period is vital, since adult cells forming within the larval body bear surface proteins not found on larval cells (Flajnik et al., 1986). PMID- 1498042 TI - Differential expression of the msp130 gene among skeletal lineage cells in the sea urchin embryo: a three dimensional in situ hybridization analysis. AB - In order to examine the ontogeny of tissue-specific expression of the msp130 gene during early embryogenesis of the sea urchin, we have developed a whole-mount, non-radioactive in situ hybridization protocol suitable for these embryos. This protocol is adapted from the existing technology of immunohistochemical localization of digoxygenin-labelled hybridization probes in tissue sections. Transcript distribution patterns in the whole embryo are seen in three dimensions, and at much higher resolution and sensitivity than can be achieved using radioactive probes and sectioned material. We have traced the ontogeny of expression of the skeleton-specific gene, msp130, during the development of Strongylocentrotus purpuratus. Transcripts are first detected at the blastula stage, in micromere-lineage cells just prior to ingression. Appearance of msp130 transcripts remains strictly limited to this lineage through the pluteus stage. Estimated from the relative intensity of staining of the PMCs of an embryo, the relative abundance of msp130 transcripts is uniform among the 32 cells of this lineage in secondary mesenchyme blastulae and in gastrulae, indicating that expression is homogeneous among these cells up to the early prism stage. However, the relative intensity of stain, and therefore abundance of transcripts, changes dramatically and in a consistent pattern among the PMCs of an embryo during prism and pluteus stages, suggesting that these cells switch from an autonomous mode of regulation of the msp130 gene, to an inductive mode. In the pluteus larva, the highest levels of expression occur in those cells associated with the rapidly growing tips of the spicular skeleton. PMID- 1498043 TI - Pulpal tissue reaction to buffered glutaraldehyde. AB - Pulpal tissue changes following pulpotomies with 2% w/v buffered glutaraldehyde in primary teeth were observed. A 3 minute single application of 2% w/v buffered glutaraldehyde was able to produce effective surface fixation. Limited penetration of the medicament left the remaining pulp tissue unaffected. The zone of fixation did not proceed apically. With time, macrophages and fibroblasts appear apical to the zone of fixation indicating the onset of replacement resorption. PMID- 1498044 TI - Lactobacilli from the dentin and saliva in children. AB - Lactobacilli were detected simultaneously in saliva, dental plaque and carious dentinal plaque in 66 children aged 5 to 15 years. The dentinal plaque samples numbered 15. It was found that Lactobacilli were present in 100% of the dentin samples, 70% of the saliva samples and 29% of the plaque samples. The DMF index and dentinal lactobacilli are systematically linked. The DMF index is weakly linked to salivary and independent of plaque lactobacilli. It is concluded that (1) dentin is responsible for the salivary hypercontamination and (2) the Lactobacillus Count could hardly be a predictive test. PMID- 1498045 TI - Early eruption and advanced root development of the permanent cuspids in a six year-old boy. AB - A case report showing the eruption of the left maxillary and mandibular permanent cuspids in a six-year-old boy, is presented. In addition, the dental age of all the permanent cuspids as seen by the eruption and tooth development suggested that the cuspids are comparable to those seen in a 13 to 14 year-old-boy. A search of the literature has not revealed any such reports. PMID- 1498046 TI - Microdontic maxillary lateral incisor: case report. PMID- 1498047 TI - Hypodontia of the primary and permanent dentition. AB - The prevalence, possible etiological factors and management of hypodontia was briefly reviewed. A report of a case of hypodontia affecting the primary and permanent lower incisors was described. PMID- 1498048 TI - Nursing caries in Head Start children, St. Thomas U.S. Virgin Islands: assessed by examiners with different dental backgrounds. AB - The purposes of this study were to determine the prevalence of nursing caries in 3- to 5-year-old Head Start (HS) children on St. Thomas, U.S. Virgin Islands and to assess the reliability of examiners with different dental backgrounds. A dentist, hygienist, and nondental HS personnel participated in a 1/2 day training session (lecture and workshop) and then independently conducted visual examinations for caries of the maxillary anterior teeth including nursing caries. Twenty-three HS personnel examined a total of 375 children; the dentist and hygienist examined a random sample of 74 and 73 children, respectively. Seventy one children received all three independent examinations. Reliability was assessed by percent agreement, sensitivity, specificity, and kappa value. The dentist found 41% of the children had caries of the maxillary incisors, which included nursing caries. The percentage of children with nursing caries was 12%. There was strong-to-good diagnostic agreement between the dentist and hygienist. The HS personnel also found that 12% of the children had nursing caries, but the diagnostic agreement between the dentist and HS personnel was only good-to-fair. PMID- 1498049 TI - Are Medicaid fraud control units the real fraud: 4. Penetrating the deceptions. PMID- 1498050 TI - Juvenile periodontitis: a review of pathogenesis, diagnosis and treatment. AB - Juvenile periodontitis (JP) and its treatment has become a critical concern to the practicing dentist. Actinobacillus actinomycetemcomitans has been diagnosed as the prime etiological agent associated with this disease. Decreased chemotaxis and phagocytosis of polymorphonuclear leukocytes have also been described in these patients. The precise treatment regimen must be individualized for each patient. In addition to aggressive antibiotic therapy, root planing, curettage or a surgical approach, with mandatory follow-up care, should be considered. This review discusses the etiology and pathogenesis of JP and recommends treatment regimens, according to patient diagnosis. PMID- 1498051 TI - Modus operandi of Planas' appliance. AB - Planas' approach to the management of a distocclusion, as applied by Simoes, is analyzed physiologically by taking into account the Petrovic-Stutzmann's cybernetic vision of facial growth. This scientifically based theorization further strengthens the clinical validity of this orthodontic ideology and procedure. The clinician, the orthodontist, the functional orthopedist or the functional orthodontist are fundamentally dependent on their knowledge about biophysics, biochemistry and mainly physiology. It is important then that they be acquainted with fundamental concepts of basic sciences as applicable to the specialty. In planning the treatment of a malocclusion, it is necessary to select the appliance or the series of them for sequential use in the correction of a intermaxillary malrelation. It is also useful to be able to predict the response to each appliance. In this case it must be considered the input (appliance in the mouth) designed to produce either displacements of the teeth or other modifications within the dentofacial complex and the output (appliance effect). According to Petrovic and Stutzmann there are 6 tissue level growth categories. Previous investigations using Frankel appliance, LSU Activator, Bionator, Chin Cup and Begg techniques, have shown that when going from the growing category number 1 to number 6 it becomes easier to stimulate the growth rate and amount of the condylar cartilage and of the posterior border of the ramus and it becomes more difficult to restrain their growth rate and amount. In other words we have also to test clinically the effectiveness of the Planas Appliance by taking into account the inter-individual variation in the tissue level responsiveness to it. (Fig. 1-4).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1498052 TI - Malocclusion, body posture, and temporomandibular disorder in children with primary and mixed dentition. AB - Occlusal factors, body posture and TM disorders were examined in forty children with primary dentition and forty children with mixed dentition. The purpose of the study was to test the hypothesis that there is a relationship between TM disorders and malocclusion, as well as that there is a relationship between body posture and TM disorders in the examined population. Clinical examination was done by two investigators, who used a stethoscope to detect TMJ sounds. The results showed that forward head position had a significant relationship to TM disorders in the mixed dentition. Also many of the occlusal factors were closely related to TM disorders in the population examined. The prevalence of TM disorders in primary dentition was 2.5% and in the mixed dentition it was 90% in the population studied. PMID- 1498053 TI - Space maintenance and endodontic follow-up: case reports. AB - Early extraction of carious primary teeth may result in functional and/or loss of arch length problems. That is the rationale behind root canal therapy and/or space maintenance after the extraction of pulpally involved primary molars. What follows is a short radiographic and photographic history of unexpected results in well established and routine space therapy treatments. PMID- 1498054 TI - Delayed retraction utilizing ceramic brackets. AB - The purpose of this study was to evaluate clinically the delay in retraction utilizing ceramic orthodontic brackets versus stainless steel brackets. Twelve patients with Class II division 1 malocclusions requiring the extraction of maxillary first premolars were employed in the study. The following observations were obtained: 1. Retraction of all cuspids bonded with ceramic brackets displayed delayed retraction when compared to their stainless steel counterparts. 2. Over a 36 week period, teeth bonded with stainless steel brackets travelled 2mm farther or 1.8 times faster than those bonded with ceramic brackets. PMID- 1498055 TI - Tricontinental agreement on less toxicology. PMID- 1498056 TI - Breast cancer: adjuvant therapy with anthracyclines. PMID- 1498057 TI - Current state of liposome-complexed drugs in the treatment of cancer patients. PMID- 1498058 TI - Cancer diagnosis disclosure in a Spanish hospital: how do they discuss treatment options? PMID- 1498059 TI - Biology and treatment of gliomas. AB - This review discusses some of the recent advances in glioma research and treatment. Our understanding of the characteristics of these tumors has been strengthened by the application of molecular biologic and genetic techniques to pathologic grading and therapy outcome. Newer attempts to correlate imaging modalities to pathologic grading are also discussed. It is anticipated that these developments will strengthen our ability to design improved treatment strategies, an essential goal inasmuch as current treatment schemes have limited benefit. More work needs to be done to understand the biology of these tumors especially the complex interactions of their cytokine expression, multiplicity of genetic abnormalities, and their local environment. Only then will be able to develop improved therapeutic interventions. PMID- 1498060 TI - New hormone-related markers of high risk to breast cancer. AB - New markers of increased risk to breast cancer are examined and related to established risk markers. The following new evidence is highlighted: (1) Increased testosterone secretion by the ovaries is currently the only major steroid abnormality shown to be associated with increased risk of both premenopausal and postmenopausal breast cancer. (2) Upper body-type obesity is a marker for both hyperandrogenaemia and hyperinsulinaemia and is associated with an increased risk of breast cancer. Upper body type obesity may already be recognised in early puberty in caucasian girls and is associated with a characteristic androgen/oestrogen profile. (3) Relative tallness in women is associated with an increased risk of breast cancer. A hypothesis is offered on the significance of these markers in the aetiology of mammary cancer in women, and also a means of testing the hypothesis. The hormonal promotion of mammary carcinogenesis is likely to be greatest between puberty and the first full term pregnancy. The presence of hyperinsulinaemia can increase the ovarian production of androgen, and the abnormal hormonal profile may stimulate proliferative activity in mammary epithelium. This may increase the risk of epithelial atypia and carcinogenesis. PMID- 1498061 TI - Randomized trial of adjuvant chemotherapy for operable breast cancer comparing i.v. CMF to an epirubicin-containing regimen [see comment]. AB - From January 1985 to December 1987, 228 women with breast cancer smaller than 3 cm were treated by surgery +/- radiotherapy. All of them had axillary node involvement (N+) and/or lacked estrogen and progesterone steroid receptors (EPR ). They were randomized in an adjuvant chemotherapy trial comparing 9 intravenous CMF courses (cyclophosphamide, methotrexate, 5FU)--113 patients--to a polychemotherapy consisting of 3 courses of MTV (mitomycin C, thiotepa, vindesine) plus 3 courses of EVM (epirubicin, vincristine, methotrexate)--115 patients. Prognostic factors were well balanced between the two treatment groups. With a 59-month median follow-up, local breast relapses are more frequent in the CMF group, but regional and metastatic recurrences are the same in the two groups. Overall survival is identical. Toxicity is different: alopecia and neurotoxicity are more frequent in the MTV+EVM group, but general and digestive toxicities are equivalent. Haematologic toxicity is greater in the CMF group, requiring more frequent dosage reductions. PMID- 1498062 TI - Phase I/II study of liposome-complexed mitoxantrone in patients with advanced breast cancer. AB - The toxicity of escalating doses of liposome-complexed mitoxantrone (LCM) was evaluated in 22 women with histological/cytological diagnosis of metastatic breast cancer (21 pts) or adenocarcinoma of unknown primary origin (1 pt). All patients but one had been pretreated with chemotherapy. LCM was given IV as a 1h infusion, repeated every 3 weeks, from a starting dose of 3 mg/m2, corresponding to 1/3 of the MELD10. An intra-patient dose escalation scheme, with an increase per cycle of 3 mg/m2 up to 12 mg/m2, and then by 2 mg/m2 was applied, treatment being continued until tumour progression, or toxicity, or up to a maximum of 6 cycles, whichever occurred first. Granulocytopenia was dose-limiting, with a GNC count of less than 0.5 x 10(3)/microliters after 30%, 28%, 50% and 50% of the cycles given at 16, 18, 20 and 22-24 mg/m2, respectively. The lowest GNC count occurred usually 2 weeks after treatment, with recovery in the following week. Gastro-intestinal toxicity, mucositis and alopecia were rare and of mild degree. Two patients, with a subtotal neoplastic involvement of the liver and a pretreatment grade 4 liver impairment, died because of acute liver failure a few days after treatment. The maximum tolerable dose was defined at 22 mg/m2 and 18 mg/m2, given every 3 weeks for 6 cycles, was the regimen recommended for phase II studies. Seven previously untreated patients with metastatic breast cancer have been so far treated. The pattern of toxicity of LCM (specific, short-lasting granulocytopenia; negligible, non cumulative non hematological toxicity) was confirmed.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1498063 TI - Cancer diagnosis disclosure in a Spanish hospital. AB - At the Clinic Hospital in Barcelona, Spain, 167 cancer patients and 380 hospital health care workers were interviewed about cancer diagnosis disclosure. Only 25 patients (15%) were correctly informed of their diagnoses. Breast cancer patients were significantly more often informed than patients with other malignancies (p less than 0.05). Two hundred seventy-two of 380 hospital health workers interviewed (71%, p = 0.00) would want to know their own diagnoses should they suffer from cancer in the future, but only 19% (p = 0.00) would want such a diagnosis revealed to their similarly afflicted relatives. This information model, based on cancer taboo, is largely preferred by these healthy people and is followed by doctors, patients and family members. To inform our patients better, the mandatory uniform disclosure of the true diagnosis is not likely to be constructive at present. In our opinion a pragmatic approach is more realistic and humane. Nevertheless, we must hope that more modern cancer education will lead to the gradual elimination of this taboo in our society. PMID- 1498064 TI - Long-term effects on pulmonary function of mantle radiotherapy in patients with Hodgkin's disease. AB - Twenty-five patients (21-45 years old) treated for Hodgkin's disease with mantle radiotherapy but no chemotherapy underwent chest radiography and pulmonary testing with spirometry, pulmonary mechanics and exercise test combined with arterial blood gas analysis, lung scintigraphy, assessment of pulmonary artery pressure with Doppler cardiography and vector ECG 10-20 years after treatment. The doses to mediastinum ranged from 35-43 (mean 40) Gy given in 26 fractions with the split-course technique. Radiographic signs of slight to moderate pulmonary fibrosis were seen in 18 patients. Minor restrictive ventilatory defects were found with decreased VC, TLC and lung compliance and increased maximal elastic recoil. Little evidence of airflow obstruction was found. Exercise capacity was decreased in three individuals but the mean value for the study group as a whole was normal. Arterial PO2 at maximum exercise was reduced but no patient had diminished hemoglobin saturation. Lung scintigraphy showed defects in 21 patients, mostly consisting of slight abnormalities at the lung periphery and apices. The perfusion seemed to be more affected than the ventilation, suggesting primary vascular lesions. Twelve patients showed signs of right ventricular hypertrophy in vector ECG and four of these had systolic pulmonary artery pressure greater than or equal to 30 mm Hg. The observed abnormalities were mostly of a minor degree and few clinically significant long term effects of mantle radiotherapy on pulmonary function were observed. PMID- 1498065 TI - Feasibility study of high-dose carboplatin and etoposide in the salvage treatment of testicular cancer. AB - Eleven patients with testicular cancer, either relapsing after or refractory to cisplatin-based chemotherapy, underwent salvage chemotherapy with high-dose carboplatin (800 mg/m2 on day 1) and high-dose etoposide (500 mg/m2 on days 1, 3 and 5). A total of 21 courses were administered. The major toxicity consisted of profound myelosuppression. There were two toxic deaths, both caused by infection during neutropenia. Bone marrow recovery was usually complete around day 26 (range 19-129). Other toxicities included mild mucositis, nausea and vomiting, and alopecia. No significant neurotoxicity or hearing loss were observed and only one patient had a moderate decrease in renal function. Nine of ten evaluable patients responded, with one complete remission, 6 partial remissions with normalization of tumor markers, and two partial remissions with over one log decrease of tumor markers. The duration of these remissions was not evaluable, since only three evaluable and responding patients did not receive additional therapy after HD-CE. All three relapsed after discontinuing chemotherapy. HD-CE has activity in relapsing or refractory testicular cancer and can be administered without bone marrow support. The regimen may thus be suitable to be used as a remission induction regimen prior to consolidation with intensive chemotherapy and autologous bone marrow transplantation. PMID- 1498066 TI - Prognostic factors for survival in patients with advanced renal cell carcinoma treated with recombinant interleukin-2. AB - A database of 327 patients with advanced Renal Cell Carcinoma (RCC) has been analyzed in order to identify potential baseline prognostic factors predicting for survival, following recombinant Interleukin-2 treatment (rIL-2). All patients received a continuous infusion (CIV). Eligibility criteria were uniform across studies, and included patients with an ambulatory performance status (PS), measurable disease, no CNS metastases, and no major organ compromise. Multivariate analyses identified baseline PS (ECOG 0 vs. 1), time from diagnosis to treatment (DTI greater than 24 months vs. less than or equal to 24 months), and the number of metastatic sites (1 vs. greater than or equal to 2, where lung, bone and other sites are considered as separate sites) as important predictors for survival. Patients can be classified into 4 subgroups, which are a function of the number of risk factors present. Median survival for each subgroup is 28, 17, 10 and 5 months, respectively. The model was validated in an independent cohort of 125 patients with RCC treated with subcutaneous (s/c) rIL-2, and predicted for survival accurately. By determining in which risk group category patients may fall, treating physicians may be better equipped to decide on patient management. The model may also be of value in order to stratify patients in randomized clinical trials. PMID- 1498067 TI - Epirubicin/dacarbazine rapidly alternated with ifosfamide in the treatment of metastatic soft tissue sarcomas. AB - Twenty-eight patients with non-pretreated metastatic soft tissue sarcomas were entered on a treatment protocol of rapidly alternating epirubicin/dacarbazine and ifosfamide: Epirubicin 100 mg/m2 d1, dacarbazine 500 mg/m2 d1 + d2, ifosfamide 6000 mg/m2 24-h infusion d15; repeated d29. Eight patients (30%) achieved partial responses, with a median duration of 8.5 months. The median time to progression was 5.5 months. Myelosuppression was the main toxicity. Only 74% of the planned dose intensity could be administered. This rapidly alternating treatment protocol is not superior to anthracycline single agent therapy. PMID- 1498068 TI - Double biochemical modulation of 5-fluorouracil by leucovorin and cyclic low dose interferon alpha 2b in advanced colorectal cancer patients. AB - Because of the different sites and mechanisms of biochemical interaction among 5 fluorouracil (5-FU), leucovorin (LV) and interferon (IFN), we hypothesized that the concomitant use of IFN could increase the activity of the 5-FU/LV combination in colorectal cancer patients. Forty-five patients were included in the study and all were evaluable for response and toxicity. They were treated with 5-FU 370 mg/sqm i.v. d 2-6; LV 200 mg/sqm i.v. d 2-6; IFN alpha 2b 3 million U im d 1-7 every 21 days. Six patients achieved complete responses, 17 partial responses, 14 had stable disease and 8 progressed on therapy for an overall response rate of 51%. Median survival has not been reached. At a median follow-up of 14 months 33 of 45 patients remain alive. Nine patients experienced toxicity grade 3 (6 diarrhea and 3 stomatitis). Our results seem to suggest that IFN could increase 5 FU/LV activity and that this combination is well tolerated. PMID- 1498069 TI - Role of radiation therapy in advanced Hodgkin's disease--as yet, an answer? Still a question? PMID- 1498071 TI - Retinoids in cancer prevention and therapy. AB - Retinoids are a class of compounds structurally related to vitamin A. In preclinical studies, all-trans retinoic acid (tretinoin), 13-cis retinoic acid (isotretinoin) and the aromatic retinoids etretinate and acitretin have preventive and therapeutic effects on carcinogen-induced premalignant and malignant lesions. Clinically, chemoprevention with isotretinoin and etretinate has been tested with some degree of success in such indications as basal cell carcinomas, squamous cell carcinomas, superficial bladder tumors and second primary tumors in patients with squamous cell carcinoma of the head and neck. Limited therapeutic success has also been achieved with retinoid treatment of precancerous and cancerous conditions of the skin, oral cavity, larynx, lung, bladder and vulva. Dramatic therapeutic effects have been observed in the treatment of acute promyelocytic leukemia with tretinoin, which leads to very high rate of complete remission. Excellent results were recently reported in the treatment of squamous cell carcinomas of the skin and cervix with a combination of isotretinoin and recombinant interferon alfa-2a (rIFN alfa-2a, Roferon-A). The mechanism of action of retinoids is through modulation of cell proliferation and differentiation. Retinoids vary in their capacity to induce differentiation and to inhibit proliferation in a series of human transformed hematopoietic and epithelial cell lines. Some cytokines potentiate the retinoid-induced cell differentiation and act synergistically with retinoids to inhibit cell proliferation. The pattern of synergism is dependent upon the combination and tumor cell line tested. The discovery of nuclear retinoid receptors has contributed substantially to the understanding of the mechanism of action of retinoids at the molecular level. Further understanding of the molecular biology of retinoids is expected to contribute to a rational design of new retinoids in the future, which in turn may result in improvements in the prevention and therapy of cancer. PMID- 1498070 TI - Towards a molecular basis for tamoxifen resistance in breast cancer. AB - Breast cancer patients who acquire tamoxifen resistance may respond to second line hormonal therapy or progress to true endocrine resistance. The biological basis for these processes are poorly understood. Following successful therapy with tamoxifen there is little evidence at relapse for change in either the host endocrine environment or drug metabolic profile to account for the development of acquired resistance. Many tamoxifen resistant tumours still retain a structurally and functionally normal oestrogen receptor (ER) and yet will grow independent of oestrogen. The oestrogen-regulated molecular events which normally govern the growth of hormone-sensitive breast cancer involve a complex autocrine and paracrine interaction between several peptide growth factors (including TGF alpha, IGF-1 and TGF beta), their receptors and signal transduction pathways. Evidence now exists that constitutive activity of many of these mediators of the mitogenic signal can bypass the cell's dependence on oestrogen and provide a mechanism for hormone-independent growth. Research into these molecular mechanisms may result in a better understanding of how to overcome the clinical problem of tamoxifen resistance. PMID- 1498072 TI - Signal transduction inhibitors as novel anticancer drugs: where are we? PMID- 1498073 TI - Randomized trial of chemotherapy versus chemotherapy plus radiotherapy for stage III-IV A & B Hodgkin's disease. AB - A total of 151 patients with previously untreated Hodgkin's disease, clinical stages III-IV A & B, were randomized to receive CVPP for 6 cycles, or CVPP plus RT 3000 cGy to previously involved areas between the 3rd and 4th cycles. CVPP consists of cyclophosphamide 600 mg/m2/i.v., vinblastine 6 mg/m2/i.v. on day 1, procarbazine 100 mg/m2/p.o. and prednisone 40 mg/m2/p.o. on days 1 to 14. Both groups displayed similar clinical characteristics at diagnosis. Sixty-six were treated with CVPP + RT (52 St III and 14 St IV) and 85 with CVPP alone (68 St III and 17 St IV). Complete remission was obtained in 57 (86%) of 66 patients who received CVPP plus RT, and in 62 (73%) of 85 patients treated with CVPP. Five and sixteen patients, respectively, achieved partial responses, while 2 in each group died during treatment. At 7 years, duration of complete remission and failure free survival were: 51% and 45% for those treated with CVPP plus RT, and 23% and 21% with CVPP alone (p = 0.0150 and P = 0.0016, respectively). Overall survival at 7 years was 71% and 58%, respectively (p = 0.1488). A dose analysis performed in 84 pts showed that 91% and 88% received full protocol doses of CPM and PCZ, respectively, in the CVPP + RT group, and 95% and 94% for CVPP. The WBC nadir was 3.5 and 3.7 x mm3, respectively. Of 25 pts on CVPP + RT who relapsed, 9 are now disease-free, 5 are alive with disease and 11 have died, and with CVPP, of 37 relapsing pts, 18 are disease-free, 5 are alive with disease and 14 are dead.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1498074 TI - Sequential methotrexate and 5-fluorouracil (FU) vs. FU alone in metastatic colorectal cancer. Results of a randomized multicenter trial. The Association of Medical Oncology (AIO) of the German Cancer Society. AB - Methotrexate (MTX) modulates 5-fluorouracil (FU) in several in vitro and in vivo experimental systems. Results of phase II studies have suggested improved response rates for the sequential application of MTX and FU in colorectal cancer. In a prospective randomized multicenter study we compared sequential MTX (300 mg/m2) and FU (900 mg/m2) using a seven-hour time interval and leucovorin rescue with FU (450 mg/m2/d for five days) in patients with previously untreated metastatic colorectal cancer. Of 172 patients randomized 159 were eligible for survival analysis and 153 for toxicity and response evaluation. Complete or partial response has been seen in 25.3% of patients receiving sequential MTX and FU and in 17.6% of those receiving FU alone (p = 0.11). There have been two long term survivors, apparently cured by MTX/FU. Overall toxicity was more pronounced with FU alone, but sequential MTX/FU caused four toxic deaths. Median survival and survival rates at one and two years were not significantly different. It is concluded that this schedule of sequential MTX and FU is no more effective than a dose-intensive treatment with FU alone in metastatic colorectal cancer. PMID- 1498075 TI - Carboplatin (CBDCA), 5-fluorouracil (5-FU) and mitoxantrone (DHAD): an effective and well tolerated regimen for metastatic breast cancer. AB - Fifty-five women with metastatic breast cancer were treated with carboplatin (CBDCA), 55 mg/m2 i.v. bolus, daily for 3 days, 5-fluorouracil (5-FU) 900 mg/m2, (max. dose 1,500 mg/day in 24-h infusion (Travenol system) daily for 3 days, and mitoxantrone (DHAD) 8 mg/m2, i.v. bolus on day 1. Cycles were administered every 5 weeks. Objective responses were observed in 25 (44%) patients (95% confidence interval: 28%-60%) with a median duration of remission of 11.5+ months (range 6.5(+)-31+). Toxicity was mild. These results reflect the fact that combination of CBDCA, 5-FU and DHAD is effective and very well tolerated as an outpatient regimen. PMID- 1498076 TI - Phase II study of edatrexate in chemotherapy-naive patients with metastatic breast cancer. AB - A phase II trial of the new antifolate edatrexate (10-ethyl-10-deaza-aminopterin) was performed in thirty-eight patients with metastatic breast cancer who had never received chemotherapy. Edatrexate was administered as a weekly intravenous bolus injection at a dose of 80 mg/m2. Sites of metastases included visceral (31%), soft tissue/lymph node/bone (51%), and bone only (18%). Thirty-two patients were evaluable for response; there were 3 complete responses (CR) and 8 partial responses (PR), yielding a response rate (CR plus PR) of 34% (95% confidence limits, 17.9% to 50.9%). Responses were seen in soft tissue metastases, in visceral metastases (liver, lung) and in one patient with bone metastases. Median duration of response was 30 weeks (range 12-66 weeks). Substantial toxicity was observed. The dose-limiting toxicities were mucositis, myelo-suppression and skin toxicity. The general toxicity profile was similar to that usually reported for methotrexate, but mucositis and skin toxicity were more pronounced. Edatrexate appears to be an active drug in the treatment of chemotherapy-native patients with metastatic breast cancer. PMID- 1498077 TI - Factors influencing complete response and survival in patients with head and neck cancer treated with platinum-based induction chemotherapy. A Hellenic Co operative Oncology Group Study. AB - One hundred fifteen consecutive patients with locally advanced carcinoma of the head and neck were treated between August 1984 and August 1989 with three cycles of either of two platinum-based induction chemotherapies, followed by local treatment. After the completion of chemotherapy 26 (23%) patients had complete responses (CR). Several pre-treatment characteristics were analyzed for a possible correlation to CR to induction chemotherapy and to survival. The following variables were closely interrelated: sex, history of smoking, alcohol abuse, histologic type, tumor site and grade. Tumor stage and negative history of smoking were correlated with CR. The variables which were individually correlated with survival were keratinization, CR to chemotherapy, alcohol abuse, histologic type, site and grade of the primary tumor, serum albumin level and tumor stage. A regression analysis after Cox's model to identify a limited set of predictors selected CR, serum albumin, tumor grade, performance status and nodal status as the most significant; when analyzing the data without the time-dependent variable CR, the factors selected by the model were serum albumin, tumor grade, performance status and tumor stage. In conclusion, serum albumin level, tumor grade, performance status and tumor stage prior to treatment can be used to define risk classes in our patient population. PMID- 1498078 TI - An outpatient phase I study of a subcutaneous interleukin-2 and intramuscular alpha-2a-interferon combination in advanced malignancies. AB - The aim of this phase I study was to exploit the potential efficacy of an alpha 2a-interferon (alpha-2a-IFN)-subcutaneous interleukin-2 (IL-2) combination, bypassing the toxicity usually associated with bolus or continuous infusion of IL 2. Therefore, nineteen patients with metastatic malignancies (7 melanomas, 6 renal cell carcinomas and 6 soft tissue sarcomas) were treated according to a dose escalating schedule of subcutaneous IL-2 combined with intramuscular alpha 2a-IFN for 5 days/week for 3 consecutive weeks. Cycles were repeated every 2-4 weeks unless disease progressed. Alpha-2a-IFN (3 MU/die) was given continuously, including during the rest weeks. IL-2 doses were started at 2 MIU/day/sqm and the MTD of 6 MIU/day/sqm was progressively reached. The dose of IL-2 was given twice daily every 12 hours. Both of the cytokines were administered in an outpatient setting. The main side effects were fever, chills, fatigue, hypotension, nausea and vomiting. Toxicity was correlated with IL-2 dose level. It was found to be mild at 2 and 4 MIU/day/sqm, while, in contrast, grade III toxicity was observed only at the highest dose of 6 MIU/day/sqm. However, this grade III toxicity was manageable and did not prevent continuation of the treatment as long as the dose was not increased above 6 MIU/day/sqm. Three patients, one with melanoma and two with renal cell carcinomas, obtained clinical partial responses. In eight patients, stable disease, and in the remaining eight, progression, were observed. The data suggest that the combined use of the two BRMs has manageable side effects and would seem to be efficacious. A phase II study at the recommended dose of 6 MIU/day is now necessary. PMID- 1498079 TI - A therapy impact questionnaire for quality-of-life assessment in advanced cancer research. AB - The first part of the validation procedure used for a Therapy Impact Questionnaire (TIQ) on quality-of-life assessment in advanced cancer patients is described. The TIQ is composed of 36 items which assess both disease and therapy impact according to four dimensions that operationally define quality of life: physical symptoms (24 items), functional status (3 items), concomitant emotional and cognitive factors (6 items) and social interaction (2 items). A global judgement expressed as "have you been feeling ill" further completes the TIQ. Patients answered each question using a 4-point verbal Likert scale: not at all, slight, a lot and very much. The TIQ was given to 1,000 consecutive patients who were no longer responsive to cancer treatment and presented symptoms due to disease progression. The compliance rate was quite high (87%). Results of confirmatory factor analysis were consistent with the operational dimensions identified during questionnaire construction. In particular, the dichotomized answers to 3 functional status items could be used as a Guttman scale. In a sub sample of 50 patients, the reproducibility of functional status items was assessed using a 7-item parallel form. The intraclass correlation coefficient obtained indicated a reasonably high reproducibility. On the basis of the analyses conducted, the TIQ appears to be a reliable and concise instrument for studies aimed to assess the effectiveness of therapies in advanced cancer patients. PMID- 1498080 TI - A pilot study of suramin in the treatment of progressive refractory follicular lymphomas. AB - Ten patients with progressive follicular lymphomas (seven with follicular mixed lymphomas, three with follicular, small cleaved cell lymphomas) with clinical indications for systemic therapy received parenteral suramin. Each had failed from one to six prior chemotherapeutic regimens and three had in addition received prior radiation therapy. All had measurable disease and nine of the ten had documented bone marrow involvement at the start of therapy. Suramin was administered at an initial infusion rate of 350 mg/m2/day, which was then modified on the basis of subsequent weekly plasma suramin concentrations in order to reach a final plasma concentrations of 250-350 micrograms/ml. Treatment cycles were repeated at eight week intervals. Nine of ten patients are evaluable for response. Five of nine evaluable patients achieved a partial remission as defined by a greater than 50% decrease in the sum of the product of all measurable lesions. Sites of response include: Peripheral (five patients) and central (four patients) adenopathy, disappearance of biopsy-proven skin involvement (one patient), malignant pleural effusions (one patient) and shrinkage of an enlarged spleen (two patients). Disappearance of B symptoms occurred in the one responder with these symptoms. Response duration varied from 3 to 9 months (mean 5.6 months) with time to subsequent systemic therapy varying from 5 to 12 months (mean 8 months). Drug related toxicity included the development of polyradiculopathy (one case), liver function abnormalities (three cases), thrombocytopenia (five cases), vortex keratopathy (two cases) and bacterial infection (two cases). We conclude that suramin has significant activity against follicular lymphomas refractory to standard chemotherapy and that its precise role in the treatment of lymphoproliferative neoplasms in general warrants further investigation. PMID- 1498081 TI - Hypersensitivity reactions to cisplatin and carboplatin--a report on six cases. AB - Anaphylactic reactions to platinum compounds are well recognised, but uncommon. These vary from true type I reactions to direct histamine release due to nonimmunological mechanisms. We present 6 cases to illustrate this--5 due to cisplatin and a report of this occurring with carboplatin--with a near fatal outcome in 3 of the cases. PMID- 1498082 TI - Specific inflammatory cell infiltration of hepatic schizonts in BALB/c mice immunized with attenuated Plasmodium yoelii sporozoites. AB - We compared immunization of BALB/c mice with radiation-attenuated versus killed sporozoites of the rodent malaria parasite, Plasmodium yoelii. We employed a suboptimal schedule of only two immunizations, in expectation that some parasites might break through the resultant low level immunity and that it might thus be possible to study the response of the host against these 'breakthrough' schizonts. As a measure of protective immunity, we used histological means to determine the percentages of challenge sporozoites prevented from completing development into hepatic schizonts within the liver. Immunization with attenuated sporozoites led to almost complete protection, whereas immunization with similar dosages of killed sporozoites led to approximately a 75% protection. Fluorescent antibody titers against sporozoites were similar in both sets of immunized animals. However, serum from mice immunized with attenuated sporozoites had a protective effect upon passive transfer into immunologically naive mice subsequently challenged with normal sporozoites; serum from mice immunized with killed sporozoites had no such effect. When mice suboptimally immunized with attenuated sporozoites were challenged, we observed breakthrough schizonts being infiltrated with inflammatory cells, primarily mononuclear cells, and neutrophils; partial depletion of CD4+ or CD8+ cells within these mice prior to challenge prevented the infiltration of breakthrough schizonts. Thus, cellular infiltration of schizonts was apparently secondary to earlier action by lymphocytes. This infiltration was also not observed in mice immunized with killed sporozoites. The more effective protective immunity induced by attenuated sporozoites could be due to their ability to release antigen into the cytoplasm of hepatocytes that they invade or their ability to continue differentiating, thereby presenting new antigens that are not seen after immunization with killed sporozoites. PMID- 1498083 TI - Adjuvant arthritis and immunity to the mycobacterial 65 kDa heat shock protein. AB - The mycobacterial 65 kDa heat shock protein (HSP65) is of critical significance in the model of adjuvant arthritis (AA). Arthritogenic and protective T cell clones obtained from arthritic rats recognized the 180-188 sequence of HSP65. Previous reports have shown that administration of HSP65 prior to disease induction led to resistance to arthritis in the AA model and in several other models of experimental arthritis. Here, we report the development of immunity to HSP65 and the critical 180-188 epitope during the course of AA. Following Mycobacterium tuberculosis (MT) immunization both antibodies and T cell responses to HSP65 were detected. Proliferative responses to the 180-188 epitope were seen exclusively in the local draining lymph node cells at day 14 after immunization. The anatomical distribution and course of T cell responses to HSP65 and its 180 188 epitope are compatible with T cell regulated control of the disease. Although lower HSP65 antibody levels were observed in the animals with severe arthritis, in individual animals no evidence was obtained for a relationship between development of HSP65 humoral immunity and arthritis severity. Nevertheless, during disease exacerbation, elicited by HSP65 immunization during disease development, elevated T cell responses against HSP65 and its 180-188 epitope were found. In contrast, we obtained evidence that successful transfer of arthritis resistance to naive recipients depends on the transfer of HSP65 specific T cells. On the basis of these results, it seems that HSP65 plays a crucial role in the T cell regulatory events involved in both the induction of, and protection against, AA.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1498084 TI - Transcription factors in mouse fetal thymus development. AB - T cell precursors from murine fetal liver enter the fetal thymus where they proliferate, differentiate, and mature. These processes are accompanied by changes in the pattern of transcription factors known to control the expression of specific genes. We have monitored the expression of five different transcription factors during mouse fetal thymus ontogeny: nuclear factor (NF) kappa B, cAMP-response-element binding protein (CREB), NF-IL-2A, msNF-AT1, and hNF-AT1. NF-kappa B binding activity was not detected in extracts from fetal liver but was present in the thymus at day 14 of embryogenesis. Thereafter, NF kappa B expression was biphasic, being maximal at 14-16 days gestation and in newborn mice, and decreased during the intermediate gestational stages and in the adult. An inverse correlation was observed between NF-kappa B binding activity in the nuclei and levels of its inactive precursor in the cytoplasm of all samples analyzed. In contrast, CREB activity was uniform throughout thymus development. Similarly, NF-IL-2A activity was detected in fetal liver and thymic extracts from different gestational stages, in approximately equivalent amounts. However, band shift experiments revealed three distinct NF-IL-2A-DNA complexes, whose relative abundance is altered during thymic ontogeny. Likewise, NF-AT1 transcription factor appears to be heterogeneous and includes representatives which are differentially (msNF-AT1) or stably (hNF-AT1) expressed during thymic development. These results are discussed in the context of present knowledge about T cell development within the thymus. PMID- 1498085 TI - The effect of cytokines and mitogens on the induction of C epsilon germline transcripts in a human Burkitt lymphoma B cell line. AB - IL-4 is known to induce a 1.8 kb constant epsilon (C) transcript in human peripheral blood mononuclear cells (PBMC). This is a C germline or 'sterile' transcript which is encoded by a germline exon (I) located 5' of the epsilon switch (S) region and the four C germline exon including 3' untranslated region. Among the human B cell lines examined, one Burkitt lymphoma B cell line, DND39 (Epstein-Barr virus negative, sIgM+, CD40+), was found to respond to IL-4 and express the C germline transcript. Induction of C germline transcript in DND39 cells was entirely dependent on the presence of IL-4. Phorbol myristate acetate enhanced its expression in DND39 cells as well as in the purified B cells in combination with IL-4. Pokeweed mitogen (PWM) enhanced the expression of C germline transcripts induced by IL-4 in PBMC but the enhancing activity was not observed when purified B cells or DND39 cells were used. Supernatants obtained from PWM-stimulated PBMC strongly enhanced the expression of C germline transcript in DND39 cells when co-stimulated with IL-4. None of the known cytokines tested mimicked this effect, suggesting that PWM may induce in T cells or monocytes a novel cytokine production that works synergistically with IL-4 and enhances the expression of IL-4-induced C germline transcripts. A similar enhancing effect was observed when anti-CD40 mAb was added to the IL-4-stimulated DND39 cells. Interestingly, transforming growth factor-beta strongly suppressed it. Taken together, DND39 cells resemble normal B cells in terms to responsiveness to IL-4 and should be a useful tool to study the molecular mechanisms of regulation of C germline transcription and class switching to IgE. PMID- 1498086 TI - Inhibition of lipopolysaccharide-induced activation of immature B cells by anti mu and anti-delta antibodies and its modulation by interleukin-4. AB - Soluble anti-Ig or anti-mu antibodies completely abrogate the lipopolysaccharide (LPS)-stimulated proliferation of purified B cells obtained from spleens of 5-7 day old mice. This provides further evidence for the powerful nature of the negative signals transduced by sIgM receptors on immature B cells. In addition, ligation of sIgD receptors (expressed by approximately 30% of these cells) by two out of three monoclonal anti-delta antibodies inhibits the response to LPS by some 50%. Ligation of sIgD on purified sIgD+ B cells (greater than 98% sIgD+) completely inhibited the LPS response of these cells. The inclusion of IL-4 in these cultures partially (with anti-mu), or completely (with anti-delta), restored the proliferative response. Immobilized anti-mu or anti-delta caused comparable levels of inhibition as the soluble antibodies: IL-4 again rescued the inhibition caused by immobilized anti-delta, but not that induced by anti-mu. These results therefore indicate that engaging either sIgM or sIgD receptors on developing B cells delivers negative (tolerogenic) signals. They also implicate IL-4 as a major (although not the only) T cell-derived influence which can modulate these signals. Finally, the data suggest that extensive cross-linking of sIgM (by immobilized anti-mu) causes more profound unresponsiveness in immature B cells, which cannot be rescued by IL-4 alone. PMID- 1498087 TI - Albumin binding proteins of endothelial cells identified by anti-idiotypic antibodies. AB - Studies were conducted to identify and localize albumin binding proteins (ABPs) in endothelial cells using rabbits polyclonal anti-idiotypic antibodies (Ab2) raised against the affinity-purified anti-bovine serum albumin IgG. Ab2 were purified by fast performance liquid chromatography. The anti-idiotypic nature of the IgG was assessed by (i) the capacity to inhibit albumin binding to its specific antibody in a dose-dependent manner, (ii) the lack of interaction with albumin, and (iii) the interaction with anti-albumin antibodies of diverse origins. The latter characteristic indicates that although polyclonal, the purified anti-idiotypic antibodies contain some of the Ab2 beta type. The binding of Ab2 to cultured bovine aortic endothelial cell surfaces was saturable and specific as demonstrated by radioimmunoassay (RIA) and immunofluorescence studies respectively. A competitive RIA was used to test whether Ab2 competed for albumin binding to bovine aortic endothelial cells (BAECs) (presumably to ABPs). It was found that Ab2 inhibited binding of [125I]albumin to BAECs in a dose-dependent fashion. Immunoblot analysis of extracts of BAECs, microvascular endothelial cells, and lung showed that both Ab2 and albumin bind specifically to two polypeptides with an apparent molecular mass of 18 and 31 kDa. In addition, upon radioiodination of BAECs apical membrane proteins, Ab2 bound specifically and immunoprecipitated restrictively two radiolabeled cell surface proteins of 18 and 31 kDa. The results provide direct evidence for the presence of the 18 and 31 kDa peptides (ABPs) on the endothelial cell membrane and/or associated structures, i.e. open plasmalemmal vesicles and uncoated pits. PMID- 1498088 TI - Tyrosine phosphorylation of IgM- and IgD-associated molecules of a human B lymphoma cell line B104. AB - We investigated tyrosine phosphorylation and structural properties of the IgM associated molecules in comparison with IgD-associated molecules in a recently established human surface IgM+, IgD+ B lymphoma cell line, B104, the growth of which was irreversibly inhibited by anti-IgM mAbs but not by anti-IgD mAbs. Tyrosine kinase activity and tyrosine phosphorylated proteins were detected in anti-IgM and anti-IgD immunoprecipitates from digitonin lysates of B104 cells with the use of an in vitro kinase assay followed by a re-immunoprecipitation experiment with anti-phosphotyrosine mAbs. Tyrosine phosphorylated proteins of 74, 58-44, 41, and 39 kDa were detected in anti-IgM immunoprecipitates, whereas tyrosine phosphorylated proteins of 74, 58-44, and 39 kDa, but not 41 kDa, were detected in anti-IgD immunoprecipitates. Crosslinking of surface IgM and surface IgD stimulated rapid tyrosine phosphorylation of different sets of proteins which included tyrosine-phosphorylated proteins of the same or similar molecular weights as those detected in the anti-IgM and anti-IgD immunoprecipitates respectively. After deglycosylation by N-glycosidase, both the IgM- and IgD associated phosphoproteins (pp58-pp39) gave rise to the same three bands of 29, 27, and 26 kDa. Proteolytic peptide mapping of these three deglycosylated proteins showed that the primary structures of the IgM- and IgD-associated molecules are identical, suggesting that the IgM- and IgD-associated phosphoproteins (pp58-pp39) are the products of the same or closely related genes. One of the products, pp41, may be associated with IgM, but not with IgD, although the same gene product may be associated with IgD in a different glycosylation pattern. PMID- 1498089 TI - Human thioredoxin/adult T cell leukemia-derived factor activates the enhancer binding protein of human immunodeficiency virus type 1 by thiol redox control mechanism. AB - Transcription from the human immunodeficiency virus type 1 (HIV-1) provirus is activated by a cellular factor, NF kappa B, recognizing the tandemly repeated 10 base-pair sequences, termed the kappa B sequence, present in the enhancer region within the viral long terminal repeat (LTR). Using electrophoretic mobility shift assay (EMSA), which demonstrates specific DNA-protein interaction in vitro, we could demonstrate that reducto-oxidative modulation of NF kappa B dramatically changes its DNA binding activity and that a cellular physiological reducing catalyst, thioredoxin (TRX) also known as adult T cell leukemia derived factor (ADF), fully restored the DNA-binding activity of the oxidized NF kappa B. We also observed that purified TRX/ADF protein could augment gene expression from HIV LTR as demonstrated by transient chloramphenicol acetyltransferase (CAT) assay. These observations confirmed the previous notion that ADF might be an inducing factor of cellular interleukin-2 receptor alpha subunit (IL-2R alpha) through the kappa B sequence that is a common central cis-regulatory element in both IL-2R alpha and HIV gene expression. These observations indicate that reducto-oxidative regulation (or redox regulation) of a cysteine residue(s) on the NF kappa B molecule might play an important role in its specific DNA interaction and that it might provide a clue to the understanding of a pathway of cellular signal transduction to NF kappa B that is independent from the known pathways involving protein phosphorylation. PMID- 1498090 TI - Bcl-2 prevents death of factor-deprived cells but fails to prevent apoptosis in targets of cell mediated killing. AB - 'Programmed cell death' has been used to describe the death of cells killed by cytotoxic T cells or growth factor deprivation. Although bcl-2 can prevent death of cells deprived of growth factor, it failed to protect cells against T cell killing. In spite of bcl-2 expression, the DNA of targeted cells was degraded into nucleosome-sized fragments. Therefore the early steps in apoptosis induced by factor deprivation differ from those triggered by cytotoxic T cells, although they share a common final pathway featuring degradation of the DNA and loss of cytoplasmic membrane integrity. PMID- 1498091 TI - Skin distribution and differential expression of transforming growth factor beta 1 and beta 2. AB - Transforming growth factor beta (TGF-beta) 1 and 2 have both become increasingly important in cutaneous biology, but their expression and distribution in human skin are not entirely clear. In this report, normal forearm skin from four volunteers was investigated for TGF-beta 1 and beta 2 immunostaining with antibodies that detect preferentially either cell- or matrix-associated forms of these peptides. Marked cell-associated TGF-beta 1 was found in the dermis, particularly around blood vessels and ducts; cellular TGF-beta 2 immunostaining was less prominent, and was predominantly around blood vessels. Neither TGF-beta 1 nor -beta 2 could be detected in the epidermis or epithelial structures, and the dermal matrix contained minimally detectable amounts of the two isoforms. In all cases, dermal matrix and cells contained greater amounts of TGF-beta 1 than TGF-beta 2. Previous studies have shown that both TGF-beta 1 and -beta 2 can induce dramatic increases in extracellular matrix, and both peptides have been implicated in the pathogenesis of fibrosis. We therefore investigated TGF-beta 1 and -beta 2 immunostaining in involved forearm skin of four patients with systemic sclerosis. Compared to normal skin, fibrotic specimens showed increased amounts of matrix and epidermal TGF-beta 1, but not TGF-beta 2. We conclude that TGF-beta 1 and -beta 2 expression in human skin is differentially regulated, and that their distribution is varied and complex. PMID- 1498092 TI - Effects of several growth factors on cultured neurofibroma cells. AB - Neurofibromatosis type 1 (NF1) is a common autosomal dominant disorder characterized by abnormalities affecting multiple tissues derived from the neural crest. The peripheral neurofibromas are numerous and sometimes reach several hundred in number. In this study, the possible involvement of several growth factors in neurofibroma growth was investigated in vitro. When explants of neurofibroma tissue were cultured, macrophage-like cells with pseudopodia migrated out first, and later took on a slender fusiform shape. These cells contained S-100 protein and were identified as Schwann cells. They did not proliferate under standard culture conditions. Nerve growth factor (NGF) was helpful in maintaining the differentiated phenotype of Schwann cells, but did not stimulate their proliferation. Immunohistochemical staining for type IV collagen revealed that some large flattened polygonal cells had a mesh of type IV collagen on the surface. These cells were perineurial cells. The proliferation of cells derived from neurofibroma was stimulated by basic fibroblast growth factor (bFGF), epidermal growth factor (EGF), and transforming growth factor alpha (TGF alpha). In comparison with skin fibroblasts, the cells derived from neurofibroma responded to these growth factors at considerably lower concentrations. Stimulation by EGF at physiological concentrations indicated the possible involvement of EGF in the development of neurofibromas. PMID- 1498093 TI - Epidermal Merkel cells in psoriatic lesions: immunohistochemical investigations on neuroendocrine antigen expression. AB - Biopsy specimens from lesional psoriatic skin and from normal controls were investigated by immunohistochemistry for the presence of epidermal Merkel cells (MC). MC were defined as epidermal cells expressing simple-type keratins, i.e. nos. 8, 18, and 19. A significant number of MC could be found at the bottom of the rete ridges of psoriatic lesions (about 19.6 MC per square mm skin surface area) and of normal skin (about 14.0 MC per square mm surface area). In contrast to normal skin, MC of psoriatic lesions were positive for synaptophysin (21.7% of simple-type keratin positive epidermal cells, i.e. MC), pancreatic polypeptide (14.8%), somatostatin (7.0%), and chromogranin A (less than 3%). The immunostaining was rather faint though significantly different from normal skin. The findings suggest that in psoriasis, epidermal MC show variations of the expression of neuropeptides compared to normal skin. Since some of the neuropeptides are thought to be involved in hyperproliferation and/or skin immunology, our findings might suggest a functional activity of epidermal MC in psoriatic lesions different from normal controls. PMID- 1498094 TI - The relationship between eosinophils, OKT6-positive cells and house dust mite (HDM) antigens in naturally occurring lesions of atopic dermatitis. AB - To determine the role of eosinophils in naturally occurring lesions of atopic dermatitis, we observed the distribution of eosinophil cationic protein (ECP) and the relationship between eosinophils, OKT6-positive cells and house dust mite (HDM) antigens. Some specimens showed many EG2-positive stains, although the accumulation of tissue eosinophils was not prominent. EG2 stains were seen not only in eosinophils but also in extracellular granules. Some macrophage-like cells of the dermis showed EG2 stains in the form of phagocytized eosinophil granules. Some EG2-positive eosinophils were in close contact with OKT6-positive cells in the epidermis and dermis. Furthermore, in three patients sensitive to house dust mite (HDM) antigen, HDM antigens invaded the skin with many EG2 positive stains. These results suggest that eosinophils play an active role in the development of eczematous lesions of atopic dermatitis. PMID- 1498095 TI - Effects of retinoids on endothelial cell proliferation, prostacyclin production and platelet aggregation. AB - In addition to their anti-inflammatory and anti-cancer activities, retinoids have been shown to affect angiogenesis, endothelial proliferation and the process of wound healing. While peripheral vascular occlusion has not been observed as an adverse effect clinically, the effects of retinoids on prostacyclin production in endothelial cells and platelet aggregation are not known. We examined the effects of tretinoin, isotretinoin and etretinate (3.3 x 10(-8) to 3.3 x 10(-5) M) on cytotoxicity by 51Cr-release assay, growth and prostacyclin in bovine carotid endothelial cell cultures, and the aggregation of human platelets induced by ADP. All retinoids showed either no or only small effects on cytotoxicity and human platelet aggregation. Prostacyclin production was not significantly affected except for tretinoin and isotretinoin at 3.3 x 10(-5) M. Endothelial proliferation was affected by all three retinoids in a dose-dependent fashion; for tretinoin and isotretinoin an inhibitory trend was noted as the concentration increased but the reverse was true for etretinate. Retinoids at 3.3 x 10(-5) M induced alterations of typical endothelial morphology; the cells became fibroblastoid. The results of prostacyclin production and platelet aggregation in the present study are consistent with the absence of peripheral vascular occlusion as a side effect clinically. PMID- 1498096 TI - Organ culture conditions of human hair follicles. AB - Experimental results revealed that although [3H]thymidine uptake in the hair bulb increased time dependently for 12 days under normal culture conditions (95% air 5% CO2 at 37 degrees C), striking morphological changes occurred in the hair bulb cells as demonstrated by histological findings. As such, organ culture conditions applicable to human hair follicles were studied utilizing observations from both histology and DNA synthesis. We found that culture conditions of 95% O2-5% CO2 at 31 degrees C were superior when compared to normal culture conditions for cultures of human hair follicles when attempting to maintain the normal morphology of hair germinative cells. The hair bulb and the germinative cells successfully maintained their normal morphology throughout the 96 and 48 h culture period, respectively. Autoradiographs of [3H]thymidine-labeled follicles showed localization in the germinative cells below Auber's critical line. Hair bulb DNA synthesis increased time dependently for 96 h after culture initiation. Under conditions of 95% O2-5% CO2 at 31 degrees C, the synthesis of DNA in hair germinative cells was observed. Such an organ culture method may prove useful for studies on the human hair growth mechanism. PMID- 1498097 TI - Production of IL-4, IL-2, IFN-gamma, and TNF-alpha by peripheral blood mononuclear cells of patients with atopic dermatitis. AB - Recently, T cell-derived cytokines have been postulated to be involved in the pathogenesis of atopic dermatitis (AD) since the synthesis of IgE is profoundly regulated by cytokines such as IL-4, IFN-gamma and IL-2. IL-4 enhances the production of IgE and in contrast, IFN-gamma inhibits this IL-4-mediated IgE production. IL-2 also prevents IL-4-induced production of IgE by a different mechanism from IFN-gamma, suggesting that the level of IgE is regulated by the quantitative balance of these antagonizing cytokines. We examined the production of IL-4, IL-2, IFN-gamma and TNF-alpha by PBMC of AD patients and non-AD controls. Although the production of IL-2 and TNF-alpha by AD patients was significantly lower than that of non-AD controls, the production of IL-4 and IFN gamma did not show significant differences between AD and non-AD individuals. There was no significant correlation between cytokine production and clinical symptoms in AD patients. There was significant positive correlation between IL-4 and IL-2 production, and between IFN-gamma and TNF-alpha production. Serum IL-4 levels showed no significant difference between AD group and non-AD group. PMID- 1498098 TI - Cloning and sequence analysis of the tyrosinase gene from a patient with tyrosinase-positive oculocutaneous albinism. AB - Tyrosinase is synthesized on membrane-bound ribosomes and transported into melanosomes through smooth endoplasmic reticulum and Golgi apparatus. Melanin polymers are produced only in melanosomes but never in smooth endoplasmic reticulum or Golgi apparatus, indicating that posttranslational modifications of tyrosinase are completed with melanosomes where tyrosinase becomes an active form. Based on a working hypothesis that tyrosinase-positive oculocutaneous albinism is a consequence of the structurally altered tyrosinase due to a point mutation in the gene of its gene coding for a glycosylation site or a membrane binding site, which leads to the impairment in the posttranslational modification of tyrosinase and its catalytic activity, we have cloned the tyrosinase gene of one patient affected with tyrosinase-positive oculocutaneous albinism and determined its nucleotide sequence. Thus demonstrated all exons' nucleotide sequence of the patient's tyrosinase gene was found to be identical to that of the wild-type gene. The results indicate that the patient's tyrosinase itself is not altered. We therefore propose that the molecular basis for the development of tyrosinase-positive oculocutaneous albinism exists as a defect in other proteins required for the activation of tyrosinase or in other regions of the tyrosinase gene. PMID- 1498099 TI - The 10th Max Grob Memorial Lecture--Zurich, September 5, 1991. PMID- 1498100 TI - Splenic cysts in pediatric patients--a report on 8 cases and review of the literature. AB - 8 cases of splenic cysts are reported: treatment was surgical in 4 large cysts (greater than 5 cm, 3 epidermoids and 1 pseudocyst), and non-operative in 4 small cysts (less than 5 cm, 3 post-traumatic pseudocysts and 1 congenital cyst, probably epidermoid). Follow-up was over a period of 3 months to 7 years. 3 among the 4 post-traumatic pseudocysts were followed up by ultrasound until resolution (3 months to 3 years), and 1 large pseudocyst was operated on due to rupture following benign trauma. 3 large cysts were epidermoid in origin, 1 was electively operated, and 2 were discovered and operated on because of complications (rupture, infection). Only one total splenectomy was performed; surgery preserved the spleen in all other cases; but 1 epidermoid cyst presents now with a recurrence. Based on this experience, we suggest frozen section of the cyst wall during surgery, to decide the type of partial splenectomy to be performed: total cystectomy or marsupialization. PMID- 1498101 TI - Massive bleeding into the upper gastro-intestinal tract in hereditary chronic calcifying pancreatitis in the child. AB - This report deals with a young girl affected with chronic hereditary calcifying pancreatitis, which gave rise to acute life-threatening arterial bleeding into the upper gastro-intestinal tract. A pancreatic pseudocyst forming in the chronically affected pancreas spontaneously perforated into the stomach, thereby eroding a gastric wall artery. We think it is conceivable that in the future this type of complication in children with pancreatitis and pseudocyst formation might occur more frequently. PMID- 1498102 TI - Echinococcus granulosus infection of the liver and lung in an 8 1/2-year-old boy. AB - We report on an 8 1/2-year-old boy with an echinococcus granulosus infection of the liver and lung, drawing particular attention to the therapy applied. This therapy consists on the one hand of medicinal treatment with Mebendazol and on the other hand of two subsequent operations with resection of the cysts. The course of the illness is illustrated by means of the most important laboratory parameters; an indication of the present serological diagnostic is also given. PMID- 1498103 TI - Clinical relevance of Hirschsprung-associated neuronal intestinal dysplasia (HANID). AB - The rate of Hirschsprung-associated neuronal intestinal dysplasia (HANID) is reported to be as high as 20-75% but no report deals with its sequelae. The aim of our study was to evaluate the influence of the retained neuronal dysplastic segment in patients with Hirschsprung's disease (HD). We report on 47 patients with HD including 11 cases with HANID (23%). All 47 children had a Duhamel procedure subsequent to colostomy and in none of the 11 cases with HANID was the neuronal dysplastic segment resected. There was no significant difference of early and late complications in both groups and the results of the mean follow-up of 5 years after the Duhamel procedure show that the patients with HANID did as well as the patients with isolated HD. It is suggested therefore that HANID may be a distinct disease compared to isolated NID and that the NID attained segment may be retained without increased risks or morbidity. PMID- 1498104 TI - Surgical significance of the duplex kidney with bifid ureter. AB - Between 1974 and 1990 in 16 children (5 boys and 11 girls) with a duplex kidney and bifid ureter surgery was indicated. The mean age of the 15 already operated patients was 7 years (0.3-12 years). 14 had uretero-ureteric reflux, 1 had a stenosis of the ureteric bifurcation, and 1 had a lower pole pelvi-ureteric junction obstruction. An interpyelic anastomosis was performed in 14 and a ureteroneocystostomy "en bloc" in 1. The follow-up was 3-10 years with a mean of 5 years. All 15 patients had normal uroradiological findings, and out of the 9 patients with longer follow-up (more than 3 years) 7 had a significantly diminished infection rate. PMID- 1498105 TI - Treatment and follow-up of vesico-ureteral reflux in patients with neuropathic bladder. AB - Vesico-ureteral reflux (VUR) is a relatively frequent and severe complication in neuropathic bladder, therefore it must be ruled out in every case, and prevented whenever possible. The Spina Bifida Center of our Institute is presently following 220 patients with neuropathic bladder, who undergo a periodical clinical and instrumental evaluation. Urodynamics has proved essential in detecting risk factors for VUR: small capacity bladders with reduced compliance, increased outlet resistance, and detrusor instability. Forty-eight cases of VUR, 38 of which were severe, were detected in a total of 166 patients reviewed for this paper. All patients with VUR were treated conservatively, attaining complete remission or improvement in 21 cases. Ten underwent surgical treatment owing to recurrent pyelonephritis or pyelo-renal reflux with severe dilatation, despite a standard pharmacological trial. PMID- 1498106 TI - Blunt injuries to liver, spleen, kidney and pancreas in pediatric patients. AB - 96 children with blunt injuries to liver, spleen, pancreas and kidney were analysed. The aim of this review was to determine the accuracy of radiologic imaging and to define clinical factors present on admission which could be predictive of major injuries resolving only by operation. Two thirds of the lesions could be treated non-operatively. Diagnostic accuracy of ultrasound examination (US) varies between 60 and 90%, depending on the type of the injured organ. Peritoneal lavage was progressively abandoned in favour of US. CT scan has a 100% accuracy in the determination of the type and the extension of the injury. Our review revealed 6 clinical factors present on admission with a statistically significant predictive value for surgical intervention. PMID- 1498107 TI - Ruptured spleen in children--15-year evolution in therapeutic concepts. AB - This is a 15-year retrospective study of 64 pediatric surgical patients with traumatic rupture of the spleen from 1976 to 1990. The overall mortality was 14% (9/64). All non-survivors had severe multiple traumata and no fatalities were attributable to splenic injury. During the first 5 years of the study, the traditional surgical approach of immediate laparotomy and splenectomy was employed. During the next 5 years we practised laparotomy with subtotal splenectomy and repair. During the final 5 years conservative management with clinical and ultrasonographic monitoring became predominant (1 splenectomy, 4 repair, 23 conservative treatments). Among the 55 survivors, 11 had splenectomy, 14 had splenic repairs and 30 were treated non-operatively. All survivors had excellent outcomes and there was only one complication: a local abscess following splenic repair. Based on a very strict protocol in conservative management, the total amount of transfused blood could be reduced remarkably during the last period. Splenectomized patients received pneumococcal vaccine and prophylactic antibiotic coverage was prescribed for febrile episodes. None of the splenectomized patients experienced septic episodes or increased rates of infection. Based on our experience, ultrasonographically monitored conservative management is the treatment of choice in most patients with splenic injury in childhood. PMID- 1498108 TI - A rare complication due to sulfuric acid ingestion. AB - The authors present a case of pyloric and duodenal obstruction in an 8-year-old child, resulting from accidental ingestion of sulfuric acid. A marked pyloric and duodenal cicatrizing stenosis resulting from ingestion of sulfuric acid is seen infrequently, especially in pediatric age. Sulfuric acid produces a coagulation necrosis of the gastric mucosa and submucosa, and the process may involve the entire thickness of the gastric wall, with subsequent ulceration and fibrosis. This dynamic pathophysiologic event imposes postponement of surgical intervention because of various time length between ingestion of acid and onset of gastric outlet obstruction (17 days to 5 years). Clinical features included postprandial epigastric distress, repeated non-bilious vomiting, and marked weight loss. The authors also discuss the various surgical procedures that were employed to relieve the obstruction. Notwithstanding a potential risk of malignant evolution, a gastro-jejunostomy is the treatment of choice because of the age of the patient, and good postoperative results are confirmed by barium studies. PMID- 1498109 TI - Obstetric fractures. AB - The purpose of this study was to determine the risk factors predisposing to an obstetric fracture, and their long-term outcome. We reviewed 28 obstetric fractures treated in the County of Vaud, Switzerland, between 1976 and 1989. There were 12 fractures of long bones, 10 clavicles and 6 depressed skull fractures. The belief that obstetric fractures occur in large babies or after breech deliveries is no longer valid. The common risk factors of these fractures are obstetric maneuvers during delivery (75% of cases), especially Cesarean sections (35%), prolonged labor (33%), and prematurity (25%). Cephalic presentation (64.2% of cases) is more frequent than breech position (32.1%). Weight, size, age of gestation, age of the mother, parity, gestity, and time of delivery cannot be considered as risk factors for obstetric fractures. For each type of fracture some specific risk factors are pointed out: maneuvers at birth for depressed skull fracture, Cesarean section, breech delivery with assistance and low birth weight for the fractures of long bones. All fractures were treated conservatively, except for skull fractures with a depression of more than 2 cm. Early consolidation is achieved within 2 weeks. Long-term prognosis for obstetric fractures is good without sequelae. PMID- 1498110 TI - Significance of arthroscopy in children with knee joint injuries. AB - Clinical and arthroscopic findings after knee joint injury were evaluated in 35 children aged 4-15 years. Arthroscopy revealed a rupture of the anterior cruciate ligament in 9 patients; two lesions were only partial. Eight children suffered from patellar dislocation. Eleven patients showed minimal synovial and cartilaginous lesions as the only cause of hemarthrosis, hydrarthrosis and clinical symptoms. Three had chondral lesions due to a dysplastic patella. The clinical diagnosis was confirmed in only 12 of 35 cases. Arthroscopic therapy was performed in 15 and open surgical intervention in 16 patients. Our results show that hemarthrosis and persisting symptoms after a knee trauma in children indicate a severe knee injury. The diagnostic procedure and treatment should be as ambitious as in adults. PMID- 1498111 TI - Fractures of the sacrum and disk herniation: rare lesions in the pediatric surgical patient? AB - Fractures of the sacrum and lesions of the intervertebral disks are seldom reported in childhood and adolescence. In our report, illustrated by three representative cases that we treated during the past six months, we show that sacrum fractures, not an easy diagnosis, may be more frequent than currently assumed, and that in quite a number of children and adolescents an anterior pelvic fracture may in fact be an unrecognized Malgaigne type pelvic fracture with a posterior fracture plane cutting through the sacrum. They may be accompanied by herniations and/or lacerations of intervertebral disks. PMID- 1498112 TI - Does lateral bending lead to bowing fracture in an infantile lower arm? AB - In a postmortem study on 50 lower arms of fetuses of the 25th week of gestation and newborn we performed three-point bending experiments to find out the stability of the lower arm after bending to the resulting fracture. Lower arms with intact soft tissue show an elastic behavior when bent from the side until fracture occurs. Applying the loading deflection diagrams we could classify the fractures into three types which differ significantly by means of bending moment, maximal deflection per unit length, and force required. PMID- 1498113 TI - Operative treatment of solitary bone cysts with tricalcium phosphate ceramic. A 1 to 7 year follow-up. AB - From 1984 to 1990 we treated 18 patients aged 5 to 15 1/2 years with solitary bone cysts of the humerus, the femur and the calcaneus. To fill the defect, tricalcium phosphate (TCP) instead of bone grafting was used. The clinical and radiological long-term results up to seven years postoperatively are reported. In 16 patients TCP was well incorporated without any adverse reaction to the synthetic material. Two patients with a recurrence of the bone cyst were successfully reoperated. We conclude that ceramics are a cheap and easy available substitute for bone grafts in the treatment of solitary bone cysts. PMID- 1498114 TI - New implantable device for long-term vascular access in children. AB - We report on our experience in the use of a new system of a totally implantable device for repeated vascular access in children, developed in 1989 by Pharmacia and named P.A.S. Port (Peripheral Access System Port). The P.A.S. Port is far smaller than other systems and has been designed for peripheral location in the arm. This avoids unsightly pectoral scars particularly in girls and allows insertion under local anesthesia. It is an interesting alternative to the Port-a Cath for children older than 5 years of age. It is easily accepted by the patient as well as by the caring team. PMID- 1498115 TI - Preliminary experiences with the Orbis-Sigma-System as a ventriculo-peritoneal shunt. AB - In the last 3 years an Orbis-Sigma system has been implanted in 40 hydrocephalic children (as a primary shunt in 28 and following another shunt system in 12). Its usefulness was tested by regular clinical examinations, head circumference measurement, ultrasonography or CT and the causes and frequency of shunt revisions. The preliminary results of a mean follow-up time of 1.4 years are discussed. PMID- 1498116 TI - Liaison psychiatry in pediatric surgery--a promising approach. AB - Liaison psychiatry in pediatric surgery is described and the experiences at the University Children's Hospital in Zurich are reported. The patients seen by the child psychiatrist in surgery are specified and compared with those seen in pediatrics. For the most part the same psychiatric diagnoses were made in both groups with some differences in frequency. It is concluded that liaison psychiatry should be implemented in pediatric surgery, as has long been the case in pediatrics. PMID- 1498117 TI - On teenage pregnancy. PMID- 1498118 TI - Passion and cadence: a commentary on the report to the Congress of the United States by the Office of Technology Assessment entitled Adolescent Health. PMID- 1498119 TI - Commentary on the report to the United States by the Office of Technology Assessment entitled Adolescent Health. PMID- 1498120 TI - Office of Technology Assessment--the role of Federal agencies in adolescent health. PMID- 1498121 TI - Commentary: thoughts of a gay pediatrician. PMID- 1498122 TI - Corporal punishment in schools. A position paper of the Society for Adolescent Medicine. PMID- 1498123 TI - The Registry of the International Society for Heart and Lung Transplantation: ninth official report--1992. PMID- 1498124 TI - Freezing preservation of the mammalian heart explant. III. Tissue dehydration and cryoprotection by polyethylene glycol. AB - Isolated rat hearts perfused with hyperosmotic Krebs-Henseleit buffer containing 60 mmol/L NaCl lose 10% of their tissue water. Perfusion of the rat hearts with Krebs-Henseleit buffer containing polyethylene glycol 8000 caused a concentration dependent reduction in tissue water. In a study of the effect of different cryoprotectants on cardiac preservation, isolated rat hearts were flushed with a cardioplegic solution (CP-14), or CP-14 with either 50 mmol/L glycerol (CP-15), or 5% polyethylene glycol (CP-16) and frozen at -1.4 degrees C for 5 hours. Thawed hearts were reperfused in working mode to assess function. There was no recovery in CP-14 hearts. Hearts treated with CP-15 recovered 39.3% +/- 2.9% (mean +/- SEM) of control cardiac output. CP-16 boosted the recovery of cardiac output to 54.4% +/- 5.7% (p less than 0.05 vs CP-15). Glycerol significantly reduced tissue ice content; PEG further decreased the ice content to 31.7% +/- 0.6%, which was distinctively lower than that in CP-14 (44.7% +/- 1.1%) and in CP 15 hearts (34.6% +/- 1.1%). Tissue water content of CP-14 and CP-15 hearts was similar (3.83 and 3.87 gm H2O/gm dry weight). Polyethylene glycol reduced the tissue water content to 3.24 +/- 0.04 gm H2O/gm dry (p less than 0.01 vs CP-14 and CP-15 by ANOVA). Thus both glycerol and polyethylene glycol offered cryoprotection to the heart explant by reducing tissue ice formation. Polyethylene glycol was superior to glycerol by dehydrating myocardial tissue and further minimizing freezing damage. PMID- 1498125 TI - Long-term hypothermic storage of the mammalian heart for transplantation: a comparison of three cardioplegic solutions. AB - We have compared the protective properties of three cardioplegic solutions (St. Thomas' Hospital, University of Wisconsin, and Bretschneider) for the long-term hypothermic preservation of the rat heart. Hearts (n = 8 per group) were excised and arrested by an infusion (10 ml at 4 degrees C) of cardioplegic solution. After 4, 6, or 8 hours of storage at 4 degrees C, they were reperfused in the Langendorff mode for 15 minutes and then in the working mode for 20 minutes. After 4 hours of storage, postischemic cardiac output in the St. Thomas' and Wisconsin groups was 68.8 +/- 4.6 and 63.7 +/- 3.0 ml/min, respectively (NS); nonischemic aerobic control cardiac output was 83.2 +/- 2.6 ml/min. In the Bretschneider group, cardiac output was only 43.4 +/- 3.6 ml/min (p less than 0.05 compared to the other groups). Extending storage to 6 or 8 hours led to further decreases in recovery of function in all groups (cardiac output in the St. Thomas' and Wisconsin groups was 53.7 +/- 3.2 and 52.2 +/- 5.1 ml/min after 6 hours and 39.9 +/- 2.2 and 45.8 +/- 2.5 ml/min after 8 hours, respectively; NS). With the Bretschneider solution the cardiac output was again lower (37.6 +/- 3.0 and 22.3 +/- 4.1 ml/min, respectively). Creatine kinase leakage tended to be greater in the Bretschneider group, but adenosine triphosphate and creatine phosphate contents were well preserved in all groups. In further studies, hearts (n = 8 per group) were infused with the three solutions and stored at 4 degrees C for 8 or 10 hours; they were then heterotopically transplanted into the abdomens of homozygous recipients. After 24 hours of reperfusion, the hearts were excised and taken for ex vivo functional and metabolic studies. Recovery of contractile function was similar in all groups, but the tissue content of adenosine triphosphate tended to be greater in the St. Thomas' and Wisconsin groups (15.0 +/- 1.5 and 14.7 +/- 1.0 mumol/gm dry weight in the 8-hour storage groups and 12.1 +/- 1.2 and 11.7 +/- 0.8 mumol/gm dry weight in the 10-hour storage groups, respectively) than in the Bretschneider groups (12.3 +/- 0.9 and 9.1 +/- 1.6 mumol/gm dry weight, respectively). Creatine phosphate content recovered completely in all groups. We conclude that all three solutions afford similar protection to the hypothermically stored rat heart, but that the St. Thomas' Hospital and University of Wisconsin solutions are marginally superior to the Bretschneider solution. PMID- 1498126 TI - Improved donor myocardial recovery with a new lazaroid lipid antiperoxidant in the isolated canine heart. AB - U74006F is a new 21-amino steroid (lazaroid) that prevents lipid peroxidation without glucocorticoid or mineralocorticoid side effects. Reperfusion injury has been reduced by the addition of various free radical scavengers and antiperoxidants to the reperfusate. To assess the effect of U74006F on reperfusion of donor hearts subjected to prolonged hypothermic ischemia, 21 isolated canine hearts were divided into three groups: control (group 1), drug (2 mg/kg) injected into the oxygenated blood perfusate immediately before 4 hours of preservation (group 2), and drug (2 mg/kg) injected 1 hour before heart isolation and again 15 minutes before reperfusion (group 3). After control left ventricular function studies (with an intraventricular balloon) and biopsy for high-energy phosphates and dry/wet ratios, the hearts were arrested with cold cardioplegia and cooled for 4 hours then reperfused for 3 hours. Left ventricular work was calculated by systolic and diastolic pressure curves, which showed a better return of function in group 3 hearts (1625, 2150, and 3493 mm Hg/ml in groups 1, 2, and 3, respectively, at 180 minutes of reperfusion; p = 0.02). This was likely the result of improved diastolic compliance in group 3. Dry/wet ratios showed increased tissue edema in all hearts at the end of reperfusion. Although high energy phosphate concentrations were not different between groups, adenosine was best preserved in group 3 (p = 0.03), suggesting reduced washout of this precursor. In conclusion, administration of U74006F before preservation and reperfusion may be useful for donor heart protection. PMID- 1498127 TI - Beneficial effect of fluorocarbon reperfusion on postoperative cardiac dysfunction of transplanted heart. AB - Fluosol DA 20% (Fluosol) perfusion was used to protect ischemic donor hearts of mongrel dogs from reperfusion injury. Fifteen orthotopically transplanted hearts, eight in the control group and seven in the Fluosol group, were studied for 3 hours after weaning from cardiopulmonary bypass. Donor hearts were arrested and immersed in 4 degrees C St. Thomas's Hospital Solution for 4 hours. The mean total ischemic time was 323 minutes (range, 298 to 345 minutes). In the Fluosol group, 200 ml of oxygenated Fluosol (37 degrees C; PO2 650 mm Hg; PCO2 35 mm Hg) was infused into the aortic root at approximately 100 ml/min just before aortic unclamping. Coronary sinus blood was analyzed for the MB fraction of creatine kinase, reduced glutathione, and oxidized glutathione. Hemodynamic and biochemical results were obtained at 30 minutes, 1 hour, and 3 hours after bypass. In the control group, during the second 30 minutes of the period after bypass, left ventricular end-diastolic pressure and stroke volume showed progressive deterioration, 54.8% increased (p less than 0.01) and 28.4% decreased (p less than 0.05), respectively. The MB fraction of creatine kinase and oxidized glutathione were increased, and reduced glutathione had declined, from 39.3 to 135.3 IU/L (p less than 0.01), from 28.0 to 33.4 micrograms/ml (p less than 0.05) and from 4.4 to 2.5 micrograms/ml (p less than 0.01), respectively. These parameters failed to recover during the next 2 hours, and massive mitochondrial degeneration was observed by electron microscopy. In the Fluosol group, these parameters maintained their baseline values, and electron microscopy showed well preserved mitochondria. The data suggested that, in the control group, initial mitochondrial dysfunction was profound, persistent for at least 3 hours, and associated with membrane hyperpermeability, leading to cardiac dysfunction. Oxygenated Fluosol perfusion better preserved cardiac and mitochondrial function. PMID- 1498128 TI - Improvement of currently used methods for lung preservation with prostacyclin and University of Wisconsin solution. AB - After 6 hours of cold ischemia the quality of lung preservation was assessed in a canine heart-lung transplant model comparing three clinically used methods for lung preservation: donor core cooling by means of extracorporeal circulation (group I); pulmonary artery flush perfusion with either Euro-Collins solution after prostacyclin application (group II); or University of Wisconsin solution after donor pretreatment with prostacyclin (group III). In all cases St. Thomas Hospital solution was used for myocardial protection. Heterotopic heart and orthotopic left lung allotransplantation was performed in three groups of six mongrel dogs each according to the method of lung preservation. After transplantation cardiorespiratory function was assessed at FiO2 of 0.4 for a maximum of 12 hours. After surgery, significantly improved oxygenation of the donor lung was observed in groups II and III, compared to group I (p less than 0.01). Between groups II and III, no significant differences were found in the oxygenation during the first 5 hours, but in the later postoperative course pO2 values decreased in group II although they remained stable on a higher level during the entire postoperative course in group III (p less than 0.05). University of Wisconsin solution for lung preservation in combination with prostacyclin donor pretreatment provides superior postoperative oxygenation of the transplanted lung compared to currently used clinical standards represented by donor core cooling and Euro-Collins flush perfusion. PMID- 1498129 TI - Long-term preservation of the heart: the effect of infusion pressure during continuous hypothermic cardioplegia. AB - Continuous hypothermic low-flow infusion of cardioplegic or other preservation solutions has been advocated for extending the maximum duration of storage of donor hearts for transplantation. We report the effect of varying the pressure during continuous infusion of St. Thomas' Hospital cardioplegic solution on functional recovery after long-term storage. Isolated working rat hearts (six per group) were aerobically perfused (20 minutes), and control indexes of cardiac function were measured; hypothermic ischemic arrest was then induced by a 3 minute infusion (60 cm H2O) of cold (7.5 degrees C) St. Thomas' Hospital cardioplegic solution. Hearts were then stored for 8 hours at 7.5 degrees C, either immersed in St. Thomas' Hospital cardioplegic solution (noninfused control) or continuously infused at varying infusion pressures with St. Thomas' Hospital cardioplegic solution, which had been both oxygenated and supplemented by the addition of glucose (11.1 mmol/L). After 8 hours of hypothermic ischemia, the rate of cardioplegic infusion was measured as an index of vascular resistance. The hearts were then reperfused (Langendorff) for 30 minutes during which creatine kinase leakage was measured. The hearts were then converted to working preparations for 20 minutes, and the recovery of contractile function was measured and expressed as a percentage of the preischemic control value. In hearts that had been subjected to continuous infusion at 6, 10, 20, 30, 40, and 60 cm H2O, the recoveries of aortic flow were 0% (p less than 0.05), 38.6% +/- 5.1% (p less than 0.05), 36.2% +/- 3.6% (p less than 0.05), 14.0% +/- 8.0%, 5.8% +/- 2.9%, and 9.9% +/- 4.7%, respectively, and the postischemic leakage of creatine kinase was 98.7 +/- 19.5 (p less than 0.05), 26.2 +/- 4.2, 15.5 +/- 3.4, 30.4 +/- 11.1, 109.8 +/- 21.8 (p less than 0.05), and 136.0 +/- 14.1 (p less than 0.05) IU/30 min/gm dry weight, respectively. In contrast, in noninfused control hearts the recovery of aortic flow was 11.1% +/- 7.5%, and creatine kinase leakage was 58.9 +/- 8.7 IU/30 min/gm dry weight. In conclusion, maximum myocardial preservation was obtained with continuous low-flow hypothermic cardioplegic infusion at pressures between 10 and 20 cm H2O. PMID- 1498130 TI - Effects of terminal cardioplegia with leukocyte-depleted blood on heart grafts preserved for 24 hours. AB - Canine hearts immersed in modified Collins solution were transplanted heterotopically (n = 23) and orthotopically (n = 15) to evaluate the effect of terminal warm-blood cardioplegia with or without leukocyte depletion. As the index for graft function, preload recruitable stroke work was measured in both series before harvesting (control) and after transplantation (percentage). The heterotopic hearts were divided into four groups (group 1 to 4) according to the preservation method; hearts were preserved for 3 hours in group 1 and for 24 hours in groups 2, 3, and 4. Simple terminal warm-blood cardioplegia was applied in group 3, and terminal warm-blood cardioplegia with leukocyte depletion was used in group 4. In the orthotopic series, five hearts were transplanted soon after harvesting (group 5) to simulate on-site transplantation, and the remaining ten hearts were transplanted after 24 hours of hypothermic preservation without and with terminal warm-blood cardioplegia with leukocyte depletion (groups 6 and 7, respectively). Among the heterotopic transplants, the percentage of preload recruitable stroke work was highest in group 4 (91% +/- 6%, 51% +/- 4%, 83% +/- 10%, 140% +/- 11% in groups 1, 2, 3 and 4, respectively). All orthotopic transplants in groups 5 and 7 were weaned from cardiopulmonary bypass without inotropic support and without significant differences in cardiac function between groups 5 and 7 (percentage of preload recruitable stroke work, 99% +/- 10% versus 102% +/- 2%; cardiac output, 122 +/- 10 versus 140 +/- 22 ml/kg/min). No orthotopic transplants in group 6 could be weaned from cardiopulmonary bypass, even with inotropic support.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1498131 TI - Donor cardiectomy for other transplantation centers. AB - Inadequate supply of donor hearts is the greatest limitation to wider utilization of heart transplantation. We performed donor cardiectomy for other transplantation centers in three cases. The donor heart functioned well in all cases, and the recipients were all discharged. Donor cardiectomy for other transplantation centers allows utilization of hearts that might otherwise be lost for transplantation. PMID- 1498132 TI - Donor-heart evaluation by monitoring the left ventricular pressure-volume relationship: clinical observations. AB - Fourteen donor hearts were assessed by measurement of dopamine requirement, basic hemodynamic parameters (for example, systolic blood pressure), and the left ventricular pressure-volume relationship. The latter function was measured by a combination microtipped manometer/conductance catheter placed in the left ventricle through the ascending aorta. With an isoproterenol dose 24 hours after transplantation as the measure of cardiac performance, multiple linear regression analysis indicated that the ratio of arterial elastance (Ea) to left ventricular end-systolic elastance (Ees), ventriculoarterial coupling (Ea/Ees), and myocardial ischemic time were good predictors of posttransplantation cardiac performance. Dopamine requirement and basic hemodynamic data were not. Twelve implanted hearts showed an Ea/Ees of less than 1.0 and showed good early (less than 24 hours) and late function. Two hearts considered on clinical grounds to be unsuitable for transplantation showed an Ea/Ees of more than 1.0. The data suggest that measurement of the left ventricular pressure-volume relationship would appear to be a clinically useful predictor of donor-heart performance after transplantation. PMID- 1498133 TI - Bench coronary angiography: a potentially useful method to assess coronary artery disease in the older donor heart without catheterization laboratory angiography. AB - To assess the diagnostic accuracy of ex vivo coronary artery arteriography, 12 sheep hearts were harvested, after random multiple coronary occlusions were created. The hearts were radiographed either in the flat (n = 6) or upright suspended (n = 6) position with the aorta cross-clamped. The aortic root was cannulated with an 18-gauge needle and flushed with cold normal saline solution. Five milliliters of iodinated contrast media was injected under constant hand pressure, and angiographic views were taken with a conventional, portable x-ray machine. The aortic root was then immediately flushed with normal saline solution under constant pressure to minimize contrast contact with the vascular endothelium. Total elapsed time including film development was 7 to 10 minutes. In hearts that were radiographed lying flat, a ventriculogram was obtained because of aortic incompetence. In hearts suspended in the upright position, normal coronary anatomy and previously placed coronary occlusions were easily detected in every heart that was read blindly by angiographers. To assess the effects of the contrast media on ventricular performance, five rabbit hearts were harvested and mounted on a Langendorff apparatus for functional analysis at controlled left ventricle volumes. Diastolic and systolic left ventricular pressures were unaffected by the dye injection. This simple and rapid method to evaluate coronary anatomy of the donor heart could be potentially useful in the assessment of older donor hearts in the operating room, thus increasing the volume of donor hearts available for transplantation. PMID- 1498134 TI - Successful heart transplantation with cardiac allografts exposed to carbon monoxide poisoning. AB - The procurement of cardiac allografts from brain-dead donors who have suffered acute carbon monoxide poisoning has, in the past, been considered inadvisable. Two patients have recently undergone successful transplantation at our institution with cardiac allografts from donors who had suffered acute carbon monoxide poisoning. Carbon monoxide poisoning is not a contraindication to cardiac allograft procurement in the setting of clinical and objective evidence of satisfactory cardiac function. PMID- 1498135 TI - Influence of recipient and donor gender on outcome after heart transplantation. AB - To investigate the effect of recipient and donor genders on the outcome after heart transplantation, a retrospective survey was undertaken of 356 patients (366 transplants: 316 males, 40 females) undergoing transplantation between January 1979 and December 31, 1989, at Papworth Hospital. Ninety-three organs came from female donors; 263 organs came from males. Twelve females (30%; 95% confidence interval 16% to 44%) and 51 males (16%; 95% confidence interval 12% to 20%) died in the early postoperative period (within 90 days of operation). To date, two females (5%) and 51 males (16%) have died in the late postoperative period. Comparison between recipient genders showed no statistically significant difference in early mortality rates from any cause or in actuarial survival overall, although fatal acute rejection was significantly more common in female recipients (7 of 40 female recipients versus 19 of 316 male recipients). The higher incidence of fatal rejection among female recipients was related to the higher proportion of female donors in this group, because recipients of female donor grafts had significantly higher mortality rates, particularly in the early postoperative period and as a result of acute rejection, than did recipients of organs from male donors. Death from rejection after the first 3 months and death from infection were not gender-related. Recipients of grafts from female donors did not suffer significantly more early morbidity, such as rejection and infection, or late morbidity in the form of coronary artery disease. Acute rejection episodes were more common in female recipients.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1498136 TI - Influence on survival after heart transplantation of contraindications seen in transplant recipients. AB - Fifty-seven patients underwent heart transplantation at our hospital between April 1986 and April 1991. In an attempt to assess the result of and the influence of contraindications seen in transplant recipients before transplantation on the outcome after transplantation, we have analyzed six of these "relative" contraindications: (1) age over 55 years (21% of patients); (2) pulmonary hypertension (pulmonary vascular resistance of more than 5 Wood units, and/or transpulmonary gradient of more than 12 mm Hg; 26% of patients); (3) renal failure (serum creatinine level of more than 2 mg/dl, and/or creatinine clearance of less than 35 ml/min; 11% of patients); (4) active infection (9% of patients); (5) diabetes mellitus (7% of patients); and (6) critical/unstable clinical condition before transplantation (25% of patients). An overall "risk score," obtained by adding one point for each contraindication, was also analyzed. Risk score was 0 (the "ideal" recipient) in 38% of patients, 1 in 25% of patients; 2 in 23% of patients; and 3 or more in 14% of patients. Actuarial survival was significantly lower for patients over 55 years of age (45% versus 68% at 18 months; p less than 0.05), for patients with elevated pulmonary vascular resistance (38% versus 72%; p less than 0.01), and for patients with kidney failure (16% versus 70%; p less than 0.01). On the contrary, survival at 18 months was not significantly different for patients with or without diabetes mellitus (50% versus 63%; not significant [NS]), active infection (60% versus 63%; NS), or critical/unstable condition (45% versus 69%; p less than 0.1).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1498137 TI - Utility of prostaglandin E1 in the pretransplantation evaluation of heart failure patients with significant pulmonary hypertension. AB - Patients with chronic heart failure frequently have pulmonary hypertension. Because severe preoperative pulmonary hypertension predicts a poor outcome after orthotopic transplantation, pulmonary vasoreactivity is evaluated frequently in the pretransplantation screening of heart failure patients. We prospectively evaluated the utility of the direct pulmonary vasodilator, prostaglandin E1, and compared it to the nonspecific vasodilators, nitroglycerin and sodium nitroprusside, in the evaluation of pulmonary hypertension in 39 heart transplantation candidates. Prostaglandin E1 significantly lowered pulmonary artery pressure, transpulmonary pressure gradient, and pulmonary vascular resistance. An adequate pulmonary vasodilator response (defined as a decline in transpulmonary pressure gradient to less than 15 mm Hg) occurred in 31 patients (79%). In a subgroup of nine patients also tested with nitroglycerin, greater reductions (p less than 0.01) in both transpulmonary pressure gradient and pulmonary vascular resistance occurred with prostaglandin E1, compared to nitroglycerin. Five of six patients who did not respond to nitroglycerin responded to prostaglandin E1. In another subgroup of 12 patients who were also evaluated with sodium nitroprusside, prostaglandin E1 produced a larger decline (p less than 0.05) in transpulmonary pressure gradient and pulmonary vascular resistance than did sodium nitroprusside. Six of eight patients who did not respond to sodium nitroprusside responded to prostaglandin E1. Based on pulmonary vasodilator response to prostaglandin E1, 27 patients were accepted on the transplantation waiting list, and eight patients underwent orthotopic transplantation. Postoperatively, acute right ventricular failure of the donor heart developed in none of these patients. Significant hemodynamic improvement occurred by 24 hours and persisted through 4 weeks of postoperative follow-up in all patients.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1498138 TI - Very high-dose prostaglandin E1 requirement for heart transplantation. PMID- 1498140 TI - Reversal of acute fulminant lymphocytic myocarditis with combined technology of OKT3 monoclonal antibody and mechanical circulatory support. AB - Reported is a case of acute fulminant lymphocytic myocarditis with profound circulatory compromise that was successfully reversed by treatment with OKT3 monoclonal antibody. The patient was supported with biventricular assist devices while being treated with the monoclonal antibody. The patient had remarkable recovery of ventricular function, which allowed for the removal of the device after 8 days of support. This case shows the success of combined technologies of monoclonal antibody and mechanical circulatory support to treat a potentially fatal disease process. PMID- 1498139 TI - Prostaglandin E1 reduces the frequency of rejection after heart transplantation. AB - This retrospective study was carried out to evaluate the effect of prostaglandin E1 on the frequency of rejection in 36 heart transplant recipients who survived orthotopic heart transplantation for 60 days or longer. The therapy for both groups was the same except group 1 (n = 12) was given PGE1 for 6 to 14 days. Indication for the PGE1 was right ventricular mismatch or failure. The prostaglandin administration started during the transplantation procedure. The dosage was 28 to 64 ng/kg/min and was tapered down from 14.7 to 32 ng later. No major side effects related to PGE1 have been observed. During the first 60 days after heart transplantation, in the group treated with prostaglandin, rejection grade 2 or higher was evident in 0.91 biopsies/patient versus 2.2 in nontreated patients, (p less than 0.05). A prolonged interval free from rejection (p less than 0.05) was observed in the patients treated with prostaglandin. PMID- 1498142 TI - Photochemotherapy in human heart transplant recipients at high risk for fatal rejection. AB - Heart transplant recipients in whom high levels of lymphocytotoxic antibodies directed towards a spectrum of histocompatibility antigens develop frequently represent difficult management problems. Recipients of multiple transplants and multiparous females generally form higher levels of panel reactive antibodies, which have been associated with fatal rejection episodes and accelerated graft atherosclerosis. In this study, two multiple transplant patients with preexistent high levels of panel reactive antibodies and two multiparous women who were considered at risk of sensitization were treated with a new form of immunotherapy termed photochemotherapy in addition to conventional immunosuppression. High levels of panel reactive antibodies have been reduced, and patients have suffered few rejection episodes and no infectious complications. This preliminary experience shows that the addition of photochemotherapy to conventional regimens may improve the clinical course of hypersensitized transplant patients without additional immunosuppressive risk. PMID- 1498141 TI - Methotrexate for the treatment of patients with multiple episodes of acute cardiac allograft rejection. AB - Of 142 cardiac allograft recipients who underwent transplantation from December 1985 to January 1991, four women and seven men (mean age, 41 +/- 14 years) required multiple (10.5 +/- 3.3) courses of antirejection treatment over a total follow-up period of 30 +/- 15 months. The underlying heart disease was cardiomyopathy in six patients and coronary disease in five patients. These patients were treated with methotrexate (10 mg/wk for 6 weeks). Rejection treatment before methotrexate therapy included six courses of OKT3, one course of antithymocyte globulin, 33 courses of high-dose steroids, and 45 courses of low dose steroids for the entire group. The average number of rejection treatments per patient before methotrexate therapy was 8.7 +/- 3.5 treatments or 0.90 +/- 0.51 treatments per month of follow-up. After methotrexate therapy the average number of rejection treatments fell to 1.7 +/- 1.1 treatments or 0.11 +/- 0.08 treatments per month of follow-up (p = 0.0002). Seven patients responded to a single course of methotrexate therapy; three patients required two courses (second course, 20 mg/wk for 6 weeks), and one patient required three courses of methotrexate therapy. The only complication associated with methotrexate therapy was one patient in whom cytomegalovirus interstitial pneumonitis developed while on therapy. Methotrexate was well tolerated and appeared to be effective in halting repeated episodes of rejection in this subset of patients who have had multiple episodes of acute rejection. PMID- 1498143 TI - Evolution of untreated mild rejection in heart transplant recipients. AB - To elucidate whether mild rejection requires treatment, we retrospectively examined the spontaneous natural history of this histologic feature without an increase of immunosuppression. During a 4-year period, 55 heart transplantations were performed in 54 patients on whom 958 endomyocardial biopsies were performed. Among these biopsies, 162 specimens showed features of mild rejection. We studied the results of subsequent biopsies performed 7 to 10 days later, without any change in immunosuppression. These revealed regression of lesions to minimal rejection in 51 cases (31%), the same histologic feature in 82 cases (51%), or progression to moderate or severe rejection in 29 cases (18%). In 82% of these cases, therefore, no aggravation of histologic feature was observed. We separated the cases in which current-study biopsies showed mild rejection into three groups according to the result of the most recent biopsy, that is, minimal, mild, or moderate-severe rejection. The percentage of good outcome was not modified by the nature of the previous biopsy specimen: 84%, if minimal rejection was preceding the study biopsy; 82%, in the cases of mild rejection; and 77%, for moderate or severe rejection. We did not find significant differences in this evolution between patients with fewer or more than two moderate or severe acute rejections in the first 4-month period after heart transplantation (respectively, 15% or 24% progression to moderate or severe acute rejection after nontreated mild rejection).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1498144 TI - Asymmetric intramyocardial lymphocytic accumulation during acute rejection in rat heart and heart-lung transplantation. AB - Lymphocytic accumulation in different areas of the myocardium during different phases of acute rejection were studied in rat heterotopic cardiac and cardiopulmonary allograft and isograft transplantation models. Indium 111-labeled syngeneic lymphocytes were injected 1 to 7 days after transplantation, and accumulation of the labeled cells in the graft was determined 24 hours later. The cardiac graft was divided into three segments: right ventricular (RV) free wall, epicardial portion of the left ventricle (LV) plus RV septum, and endocardial portion of the LV. In the subsequent heart-lung transplantation group, the LV epicardial portion plus RV septum segment was subdivided into LV epicardial portion and RV septum. Lymphocytic accumulation in each segment was compared between three groups according to the day the animal was killed after transplantation: days 2, 3 (group 1), days 4, 5 (group 2), and days 6, 7, 8 (group 3). Lymphocytic accumulation caused by rejection in group 1 and group 2 of both the cardiac and cardiopulmonary allografts showed significantly different intramyocardial distribution (p less than 0.01). Lymphocytic accumulation was consistently highest in RV free wall and lowest in LV endocardial portion. In group 3 specimens, lymphocytic accumulation was symmetrical in both the cardiac and cardiopulmonary allografts. In the cardiac allograft, the lymphocytic accumulation increased sharply on day 4 then declined to a nadir. This transient increase was not so pronounced in the cardiopulmonary allografts. The significantly decreased intramyocardial lymphocytic accumulation in group 2 of the cardiopulmonary allografts when compared with the cardiac allografts (p less than 0.01) is compatible with the clinical observation of a lower incidence of acute heart rejection in heart-lung transplant recipients. These data show an asymmetric accumulation of lymphocytes during acute heart rejection, which is due to increased lymphocytic affinity for the RV free wall. PMID- 1498145 TI - Ventricular dysrhythmia and heterotopic heart transplantation. AB - Heterotopic heart transplantation is an alternative option in end-stage heart disease. We present a patient with a heterotopic allograft that maintained hemodynamics at the period of a malignant ventricular dysrhythmia and supports the notion that these otherwise lethal dysrhythmias of the native heart may not carry the same risk of sudden heart death in patients with heterotopic heart transplantation. PMID- 1498146 TI - Ventricular fibrillation during acute rejection after heart transplantation. AB - The case of a 46-year-old patient who underwent orthotopic heart transplantation for treatment of end-stage heart failure as a result of ischemic heart disease is reported. Four months after transplantation a grade II rejection episode was complicated by ventricular fibrillation. Lidocaine and procainamide intravenously did not effectively prevent recurrence. An increase of antirejection therapy in combination with flecainide acetate effectively prevented further episodes of ventricular fibrillation. This case demonstrates that recurrent ventricular fibrillation can be a complication of acute rejection. PMID- 1498147 TI - Pacing requirements after orthotopic heart transplantation: incidence and related factors. AB - To assess the incidence of severe bradyarrhythmia and pacing requirements after orthotopic heart transplantation, as well as the possible causal mechanisms, we have reviewed our experience on 52 consecutive transplant patients. The overall incidence of bradyarrhythmia requiring pacing for at least 24 hours after transplantation was 27% (14 patients). The conditions of three of them required pacing for less than 1 week; the conditions of the other 11 patients (21%) required pacing for more than 1 week. Normal sinus rhythm resumed in all but four patients within 3 weeks; a permanent pacemaker was implanted in these four patients (7.6% of all 52 patients and 28% of patients requiring temporary pacing). Late complete heart block associated with acute rejection developed in two patients whose conditions required implantation of a permanent pacemaker. The age and sex of the recipient and donor were similar for patients with or without bradyarrhythmia. The percentage of patients with or without bradyarrhythmias taking amiodarone before transplantation (57% and 46%, respectively), total ischemic time (133 +/- 33 and 123 +/- 37 minutes, respectively), and cardiopulmonary bypass time (117 +/- 17 and 132 +/- 65 minutes, respectively) were not significantly different for either group of patients. The initial temperature of cardioplegic solution for organ storage and the preimplantation myocardial temperature were, however, significantly lower in patients whose conditions required pacing immediately after transplantation than in those whose conditions did not require pacing (5.3 +/- 1.7 degrees C versus 6.5 +/- 1.5 degrees C, p less than 0.05, and 3.9 +/- 1.6 degrees C versus 5.7 +/- 2.6 degrees C, p less than 0.01, respectively).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1498148 TI - Successful use of the total artificial heart as a bridge to transplantation with no mediastinitis. AB - High rates of infection, especially mediastinitis, have been reported with the use of the total artificial heart (TAH), thereby limiting its usefulness. We have used the TAH as a bridge to transplantation with only minor infectious complications and a zero incidence of mediastinitis. Between February 1988 and August 1990, the TAH was inserted at Loyola University Medical Center in 19 patients, ages 16 to 64 years (mean, 44 years). Seventeen patients (89%) underwent transplantation within 1 to 34 days (mean, 9.8 days). Of the patients who did not undergo transplantation, one was brain dead and the other died of bleeding diathesis. Early (30-day) deaths occurred in two patients (11.7%): acute rejection at 18 days and multiple cerebral infarcts at 14 days. Three late deaths (17.6%) occurred: one patient, cytomegalovirus and pneumocystis pneumonia at 4 months; one patient, bronchopneumonia and multisystem failure at 9 months; and one patient, chronic rejection at 14 months. Minor infectious complications during the TAH implantation included Enterobacter pneumonia treated with antibiotics and positive sputum cultures (Escherichia coli; Candida), with no clinical evidence of infection in two patients. No cases of mediastinitis occurred either while the TAH was implanted or after transplantation. All patients were on antibiotics while the device was in place. CONCLUSION: Our experience with the TAH shows this to be an excellent device for successful bridging of patients for heart transplantation. We have had minimal infectious complications and none directly attributed to the use of this device. This device should continue to be used safely as a bridge to transplantation. PMID- 1498149 TI - Successful double bridge to transplantation with the Thoratec ventricular assist device. AB - A 34-year-old woman was successfully bridged to heart transplantation after 5 days of biventricular support on the Thoratec system. Acute graft failure necessitated immediate replacement of biventricular support, which continued for 12 days until successful retransplantation occurred. Uneventful recovery led to discharge from the hospital on postoperative day 18. PMID- 1498150 TI - Nocardia otitidiscaviarum (caviae) infection in a heart transplant patient presented as having a thigh abscess (Madura thigh). AB - The first case of disseminated infection with Nocardia otitidiscaviarum in a heart transplant patient is reported. The clinical spectrum and treatment of infections with N. otitidiscaviarum is discussed, including our patient's apparent response to imipenem/cilastatin. PMID- 1498151 TI - Dactylaria infection of a human being: pulmonary disease in a heart transplant recipient. AB - We describe a case of pulmonary abscess caused by Dactylaria constricta in a heart transplant recipient. A 30-year-old man with a 1-month history of fever and cough was found by computed tomographic scan to have a cavitary lesion in the lingular segment in the upper lobe of his left lung. Culture of a needle biopsy specimen yielded a pure culture of D. constricta. The patient was successfully treated with systemic amphotericin B therapy, which resulted in resolution of the clinical symptoms and of the cavitary lesion. PMID- 1498152 TI - Hemodynamically significant suture line obstruction immediately after heart transplantation. AB - Mechanical complications after heart transplantation are uncommon. We describe a case of hemodynamically significant suture line obstruction that was recognized immediately after heart transplantation using transesophageal echocardiography. Transesophageal echocardiography has proved to be a powerful tool in recognizing mechanical complications in the early posttransplant period. PMID- 1498153 TI - Bladder cancer. AB - In the search for sensitive and specific tumor markers for bladder carcinoma, expression of various oncogenes and gene products (such as c-erb B-2, p53) and epidermal growth factor receptor merits particular attention. Although the results are not yet conclusive, important predictive markers are about to emerge from ongoing studies in this field. Bacillus Calmette-Guerrin treatment in superficial bladder cancer is probably the most successful immunotherapy in humans. But there is still a large knowledge deficit in the issues of optimal dose schedule and mechanisms of action. Although promising results of neoadjuvant chemotherapy in patients with invasive bladder cancers are reported, we must be cautious about changing our conventional approach until the results of large scale, controlled, randomized studies evaluating the survival are published. PMID- 1498154 TI - Head and neck cancer. PMID- 1498155 TI - Recent advances in epidemiology of head and neck cancer. AB - Cancer of the oral cavity is an important contributor to the overall international cancer burden, especially in the developing countries. Smoking cessation, moderation of alcohol consumption, and increased consumption of fruits, and probably vegetables, have been identified by epidemiologic studies as three actions that could lead to the prevention of approximately three fourths of cases in Western countries. Similar effects could be brought about in developing countries through cessation of cigarette smoking and, where appropriate, betel quid chewing and increased consumption of fruits and vegetables. Since this disease is increasing in frequency in many countries, it is important to implement these health education messages. A similar situation holds true for larynx cancer. Clearly many head and neck cancers are preventable and it is worth repeating that prevention should become an epidemiologic priority. There are exciting prospects of effective chemoprevention opportunities in head and neck cancer, with a number of compounds having activity. Further developments in this important area are awaited. PMID- 1498156 TI - Experimental head and neck oncology. AB - The field of experimental head and neck oncology continues to expand in both scope and meaningful observations. During the past year, research has focused intensively on factors responsible for disease development, genetic alterations that contribute to cancer progression, tumor growth factors and their modulation, and the biologic and clinical significance of cell-surface antigen expression. In the field of carcinogenesis, various dietary components that either promote or inhibit head and neck cancer development have been identified. Clinical trials that utilize various vitamins and their precursors such as beta-carotene have been reported. Genetic studies have demonstrated that head and neck cancers are heterogeneous in their oncogene expression; potentially, a reflection of the differential effect of various environmental carcinogenic exposures. Finally, the relationship between modulation of normally occurring cell-surface antigens and tumor aggressiveness has been demonstrated by several investigators throughout the past year. Significantly, animal models and human clinical trials have demonstrated that modulation of cell surface components by biologic agents alters the behavior of head and neck cancer and its relationship to the host. PMID- 1498157 TI - Pathology of squamous carcinomas of the head and neck. AB - Recent publications have been critically reviewed to illustrate some of the newer approaches that may eventually provide more precise prognostic information from tumor biopsies. Examples include changes in expression of various surface antigens, DNA ploidy, and alterations at the level of molecular genetics, eg, gene amplification. Other molecular changes in tumor tissue, such as point mutations and loss of normal tumor suppressor genes, are also giving clues to underlying carcinogenic mechanisms. PMID- 1498158 TI - Head and neck cancer surgery. AB - This review presents several areas of current interest in head and neck oncology including endoscopic and conservation management of early laryngeal cancer, intraoperative radiotherapy, and microvascular reconstruction techniques. Endoscopic treatment of early laryngeal cancer using the CO2 laser has been shown to be effective in several recent studies, and improved laryngeal reconstruction techniques following conservation laryngeal surgery have resulted in improved functional results. Intraoperative radiotherapy for head and neck carcinoma has received more attention recently, with encouraging results for the treatment of advanced and recurrent skull base and head and neck tumors. New techniques of free flap reconstruction following surgery for head and neck cancer continue to result in improved rehabilitation. PMID- 1498159 TI - Chemotherapy in head and neck cancer. AB - The role of chemotherapy in the management of patients with head and neck cancer continues to evolve. Single-agent methotrexate or cisplatin, or the combination of cisplatin and infusional fluorouracil can be considered standard therapy for patients with recurrent disease. Neoadjuvant chemotherapy is being actively pursued. Although enhanced survival has not yet been demonstrated, the goal of organ preservation has been achieved for patients with laryngeal cancer. Because of the high incidence of locoregional failure, concomitant chemoradiotherapy is also under investigation. This treatment approach has already been suggested to result in prolonged survival in randomized studies and holds promise for the future. PMID- 1498160 TI - Radiotherapy, hyperthermia, and phototherapy for central nervous system tumors. AB - Many new modalities and increasing data have become available in the treatment of brain tumors. We will review the growing experience with newer treatment modalities such as brachytherapy, radiosurgery, hyperthermia, and photodynamic therapy. PMID- 1498161 TI - Surgery, radiation therapy, and chemotherapy for metastatic tumors to the brain. AB - Recent literature has confirmed patient age, Karnofsky status, and the extent of extracerebral tumor as independent prognostic variables in patients with cerebral metastases. In a good-risk population, surgery followed by radiation therapy is superior to radiation alone for treatment of patients with solitary metastases. Stereotactic radiosurgery is feasible in the same select patient population, but questions regarding the extent of delayed toxicity, tumor response, and the impact on quality of life and longevity remain to be answered. Studies of external beam radiation therapy for patients with brain metastases have shown that 1) misonidazole does not improve the response rate, quality of life, or duration of survival, 2) 5 Gy for six fractions and 3 Gy for 10 fractions produce similar results, and 3) reirradiation at doses of 25 Gy for tumors progressing after initial radiation may be feasible in a selected population of patients. Chemotherapy can affect regression of brain metastases in patients with small cell lung and breast carcinoma, as well as melanoma, but the overall contribution to the quality and duration of the patient's life compared with radiation alone is unknown. Intracarotid chemotherapy is feasible for patients with brain metastases, but substantial toxicity precludes its use outside of an investigational setting. Brain metastases remain an important cause of morbidity and mortality for patients with cancer, but the majority of patients still succumb to widespread systemic disease. The goal of treatment of brain metastases should be palliation with minimal infringement upon the patient's quality of life. PMID- 1498163 TI - Genitourinary system. PMID- 1498164 TI - Head and neck. PMID- 1498162 TI - Immunotherapy and monoclonal antibody therapies. AB - High-grade malignancies of the central nervous system continue to be refractory to multimodality therapy. Immunotherapy with monoclonal antibodies, biologic response modifiers (eg, interleukin-2), and autologous, activated lymphocytes offer the potential for more selective therapy. Current research is likely to help overcome obstacles inherent in current monoclonal antibody therapy, including cross-reactivity with normal tissues, impermeability of the blood-brain barrier, and immunogenicity of murine-derived monoclonal antibodies. Treatment with adoptive cellular therapy and biologic response modifiers has been limited by low killing activity and specificity of the activated lymphocytes, limited infiltration of implanted cells, and the toxicity associated with systemically administered biologic response modifiers. Improved specificity and killing efficacy of activated lymphocytes will allow integration of cellular immunotherapy into the treatment of central nervous system malignancies. PMID- 1498165 TI - Brain and nervous system. PMID- 1498166 TI - [Current panorama of human infections caused by diphtheroid bacteria]. PMID- 1498167 TI - [Pneumonia caused by non-opportunistic bacteria in patients infected with HIV. Incidence and evaluation of a non-invasive approach]. AB - BACKGROUND: Pneumonia due to pathogenic bacteria is common in HIV infected patients. However, a global overview has not been yet performed and also the effectiveness of a non-invasive approach has not been tested. PATIENTS AND METHODS: An open study was conducted in 1989 including all HIV infected patients with a presumptive or definite diagnosis of bacterial pneumonia. Fiberoptic bronchoscopy procedures were used only in patients with a difficult diagnosis and/or problems in their clinical evolution. Clinical and biological data were compared among different etiologic groups, and their evolution was also recorded in relation with the use of non-invasive procedures. RESULTS: Among a total of 302 admissions of HIV infected patients, 113 developed a primary or secondary respiratory tract infection. Forty-three of those were bacterial pneumonia episodes. Etiologic diagnosis was achieved with non invasive methods in 18 cases (42%). Blood cultures were the most effective method used. Streptococcus pneumoniae was the most frequently identified microorganisms (9 cases, 21%). The identification of other bacteria was linked with more severe forms of disease regarding immunologic (leukopenia, p less than 0.001; T4 lymphopenia, p less than 0.05), and respiratory parameters (hypoxemia, p less than 0.05). Two deaths were directly related with pneumonia of known etiology. CONCLUSIONS: Bacterial pneumonia is the most frequent respiratory infection in HIV infected patients. An initial non-invasive approach yields a reasonable percentage of etiologic diagnosis and is not related with a poorer outcome. PMID- 1498168 TI - [Serological diagnosis of pulmonary tuberculosis using ELISA and the A60 antigen]. AB - BACKGROUND: Study of the utility of a serologic technic in the clinic diagnostic of the pulmonary tuberculosis. METHODS: An indirect enzyme-linked immunosorbent assay (ELISA) for detecting serum antibodies (IgG) against the antigen A60 has been applied to 170 tuberculosis patients (151 adults and 19 children) and 35 healthy children not protected with BCG. RESULTS: The ELISA results obtained with tuberculosis patients were: 84.8% positive IgG in adults and 21.1% in children. The percentage of serologically positive cases in healthy children against the antigen A60 was 11.5%. All the results were statistically significant (p less than 0.01). CONCLUSIONS: This test can be successfully applied as a support technique in the diagnosis of pulmonary tuberculosis in adults, it will be necessary to know the endemic situation in each community analysed. PMID- 1498169 TI - [High-pressure liquid chromatography versus a radiometric method in the identification of aminoglycoside-acetylating enzymes]. AB - BACKGROUND: High Pressure Liquid Chromatography and a radiometric method for detecting and iso-enzyme identification of aminoglycoside-acetylation enzymes were compared. HPLC determines the acetylating activity of an enzyme by using its reaction product. MATERIAL AND METHODS: Three reference strains that produce AAC (3)-I, AAC (6')-IV and AAC (2') and 15 strains isolated from patients. Identification was performed using radiometric and HPLC method in all cases. RESULTS: References strains: The enzymes produced by these strains were correctly identified with HPLC. Patient's strains: All give positive acetylase screening results with the chromatographic method, with holding time peaks that allows the identification of at least three different compounds. Identification at isozyme level was possible in all cases. In 14 out of 15 strains the results were the same using either technique. Radiometric method could not identify the enzyme of one strain. CONCLUSION: HPLC is a useful technique for isoenzyme identification of aminoglycoside-acetylation enzymes. The results were easily interpreted when compared to those of radiometric method. The group identification was possible with sisomycin. PMID- 1498170 TI - [Effect of chemotherapy on the antibody response to A60 antigen]. AB - BACKGROUND: Study of the serologic response in two groups of patients with pulmonary tuberculosis: with and without treatment. METHODS: Antibodies (type IgG) against the A60 antigen were studied in 103 patients with pulmonary tuberculosis: 46 without specific treatment and 57 after the application of the chemotherapy. RESULTS: 81.6% of the patients showed antibodies against the A60 antigen and 60.2% were strongly positive; 32.6% and 41.3% of the patients without treatment were negative and strongly positive respectively. In the patients with treatment this results were 7% and 75.4%. The differences found between both groups were statistically significant (p less than 0.001). CONCLUSIONS: It is concluded that the application of the specific treatment modify in a high percentage the response of antibody against A60 antigen and which reduced the false negatives response, this fact could condition the clinic utility of the test. PMID- 1498171 TI - [Endocarditis caused by Lactobacillus]. AB - Endocarditis due to Lactobacillus is rare. Its main features were a subacute course and greater difficulties for achieving a complete recovery even using appropriate antimicrobial therapy with serum levels above MIC. We present one case of Lactobacillus endocarditis in a patient with allergy to penicillin, due to a vancomycin-resistant strain. She was successfully treated with clindamycin and gentamicin. We emphasize the need and importance of sensitivity tests and antibiotic tolerance when choosing an optimal treatment for this infection. PMID- 1498172 TI - [Bacteriology of mucoviscidosis during a 5-year period]. AB - BACKGROUND: We have studied the bacteriology of mucoviscidosis cases from 1985 to 1989. MATERIAL: A total of 336 samples from 50 patients (median age: 7 year, range: 1 day-18 years) with mucoviscidosis were studied. RESULTS: The most frequently isolated microorganisms was Pseudomonas aeruginosa (59.2%), followed by Staphylococcus aureus (19%) and Haemophilus influenzae (18.4%). In patients younger than 1 year of age other different microorganisms were identified in 61.1% of cases, but S. aureus (11.1%) and Pseudomonas aeruginosa (5.5%) were also isolated. The incidence of Pseudomonas cepacia (0.6%) is low in our environment. We did not isolate any Legionella sp. strain. PMID- 1498173 TI - [Evaluation of an immunoenzyme technique for the detection in feces of the Giardia intestinalis antigen]. AB - An evaluation is made of the utility for the diagnosis of giardiasis of an enzyme immunoassay (EIA) that detects the GSA65 specific antigen in feces, as compared with the formalin-ether sedimentation test. Within the context of a longitudinal study on intestinal parasitization, 147 fecal samples from children attending 7 day care centres in the city of Salamanca were studied. The feces were examined a few hours after collection by the sedimentation technique and conserved in 10% formol. They were later studied by the EIA method. G. intestinalis was detected by microscopy and/or EIA in 26 of the 147 fecal samples (17.7%). Both assays were positive in 22 of the 26 cases detected (84.6%) and the remaining 4 cases were positive only by EIA (4/26; 15.4%). The EIA assay, using visual reading and very simple to implement, showed sensitivity, specificity, positive predictive and negative predictive values of 100, 96.9, 84.6 and 100%, respectively. PMID- 1498174 TI - [Surgical bacteremia. Analysis of 210 episodes with special attention to factors influencing prognosis]. AB - From January 1984 to April 1987, we have prospectively studied 210 consecutive episodes of bacteremia recorded in patients who underwent major surgical procedures. The incidence rate was 6.4 episodes/1000 surgical procedures. Men were responsible of 73.8% of episodes. The highest incidence was recorded in general surgery patients and the lowest in Ob & Gyn patients. Bacteremia-related mortality was 15.2% (overall mortality 29.5%). The five most common microorganisms isolated were: Staphylococcus epidermidis (17.7%), Staphylococcus aureus (14.7%), polymicrobial flora (13.3%), Escherichia coli (11.4%) and Pseudomonas sp. (9.5%). The common sources of bacteremia were intravascular devices (34.7%), surgical wound infection (28.5%) and urinary tract infection (12.8%). Multivariant analysis identified six variables that influence an adverse prognosis: complications, source of sepsis in a joint or unknown, admission in trauma or vascular surgery department, development of sepsis between the second and eight postoperative day, chronic illness or fatal underlying disease and sepsis after clean surgical procedures. PMID- 1498175 TI - [Species and biovars of the genus Brucella. Etiology of human brucellosis in Spain]. PMID- 1498176 TI - [Anaphylaxis and hepatomegaly in a 22-year-old patient]. PMID- 1498177 TI - [Subconjunctival hemorrhages and fever]. PMID- 1498178 TI - [Cutaneous lesions in a Spanish man from Zaire]. PMID- 1498179 TI - [Evolution of antibiotic sensitivity in Brucella melitensis]. PMID- 1498180 TI - [Infection of a permanent vascular catheter by Corynebacterium xerosis]. PMID- 1498181 TI - [Candida endophthalmitis. Is fluconazole treatment adequate?]. PMID- 1498182 TI - [False negative computerized axial tomography in the early diagnosis of pyogenic sacroiliitis]. PMID- 1498183 TI - [Recurrent bacteremia caused by Streptococcus agalactiae in a patient with recurrent cellulitis]. PMID- 1498184 TI - [Meningitis caused by Bacillus cereus]. PMID- 1498185 TI - [Habitual presence of non-01 Vibrio cholerae in the aquatic environment]. PMID- 1498186 TI - Universality in neural networks: the importance of the 'mean firing rate'. AB - We present a general analysis of highly connected recurrent neural networks which are able to learn and retrieve a finite number of static patterns. The arguments are based on spike trains and their interval distribution and require no specific model of a neuron. In particular, they apply to formal two-state neurons as well as to more refined models like the integrate-and-fire neuron or the Hodgkin Huxley equations. We show that the mean firing rate defined as the inverse of the mean interval length is the only relevant parameter (apart from the synaptic weights) that determines the existence of retrieval solutions with a large overlap with one of the learnt patterns. The statistics of the spiking noise (Gaussian, Poisson or other) and hence the shape of the interval distribution does not matter. Thus our unifying approach explains why, and when, all the different associative networks which treat static patterns yield basically the same results, i.e., belong to the same universality class. PMID- 1498187 TI - Human cone-pigment spectral sensitivities and the reflectances of natural surfaces. AB - The evolution of visual pigment spectral sensitivities is probably influenced by the reflectance spectra of surfaces in the animal's environment. These reflectances, we conjecture, fall into three main classes: i. Most inorganic and many organic surfaces, including tree bark, dead leaves and animal melanin pigmentation, whose reflectance increases gradually as a function of wavelength. ii. Living leaves, which contain chlorophyll, have a sharp reflectance peak at about 555 nm. iii. Flowers, fruit and other signaling colours that have co evolved with animal vision typically do not reflect strongly at the same wavelength as leaves, and present a colour contrast against a leafy background. These three spectral functions we call 'grey-red', 'leaf-green' and 'leaf contrast' respectively. This simple categorisation allows us to interpret the spectral tuning of human cone pigments in a way that might not seem possible given the wide variety of colours present in nature. In particular L-(red) cones will capture the highest possible proportion of photons reflected by leaves, and M-(green) cones will capture about 10% fewer photons both from leaves and from 'grey-red' surfaces. These observations have some clear implications for our understanding of the evolution of trichomacy and the trade-off between chromatic and luminance vision in Old-World Primates. PMID- 1498188 TI - Average phase difference theory and 1:1 phase entrainment in interlimb coordination. AB - The dynamics of coupled biological oscillators can be modeled by averaging the effects of coupling over each oscillatory cycle so that the coupling depends on the phase difference phi between the two oscillators and not on their specific states. Average phase difference theory claims that mode locking phenomena can be predicted by the average effects of the coupling influences. As a starting point for both empirical and theoretical investigations, Rand et al. (1988) have proposed d phi/dt = delta omega--K sin phi, with phase-locked solutions phi = arcsin(delta omega/K), where delta omega is the difference between the uncoupled frequencies and K is the coupling strength. Phase-locking was evaluated in three experiments using an interlimb coordination paradigm in which a person oscillates hand-held pendulums. Delta omega was controlled through length differences in the left and right pendulums. The coupled frequency omega c was varied by a metronome, and scaled to the eigenfrequency omega v of the coupled system; K was assumed to vary inversely with omega c. The results indicate that: (1) delta omega and K contribute multiplicatively to phi; (2) phi = 0 or phi = pi regardless of K when delta omega = 0; (3) phi approximately 0 or phi approximately pi regardless of delta omega when K is large (relative to delta omega); (4) results (1) to (3) hold identically for both in phase and antiphase coordination. The results also indicate that the relevant frequency is omega c/omega v rather than omega c.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1498189 TI - Sensory segmentation with coupled neural oscillators. AB - We present a model of sensory segmentation that is based on the generation and processing of temporal tags in the form of oscillations, as suggested by the Dynamic Link Architecture. The model forms the basis for a natural solution to the sensory segmentation problem. It can deal with multiple segments, can integrate different cues and has the potential for processing hierarchical structures. Temporally tagged segments can easily be utilized in neural systems and form a natural basis for object recognition and learning. The model consists of a "cortical" circuit, an array of units that act as local feature detectors. Units are formulated as neural oscillators. Knowledge relevant to segmentation is encoded by connections. In accord with simple Gestalt laws, our concrete model has intracolumnar connections, between all units with overlapping receptive fields, and intercolumnar connections, between units responding to the same quality in different positions. An inhibitory connection system prevents total correlation and controls the grain of the segmentation. In simulations with synthetic input data we show the performance of the circuit, which produces signal correlation within segments and anticorrelation between segments. PMID- 1498190 TI - The emergence of long-lasting transients of activity in simple neural networks. AB - The question was investigated whether long-lasting transients of activity, observed to occur in the intact cerebral cortex (EEG slow (delta) waves and 'K' complexes) as well as in isolated tissues cultured in vitro, can also emerge in a model network of excitatory and inhibitory cells. We show that such transients can indeed occur even if the cells do not have built-in slow kinetics. For certain parameter settings, the network is in a bistable state in which periods of increased activity (long-lasting transients) alternate with minimal activity. Transients are triggered by spontaneously firing cells ('noise'), which, rather than via a build-up of recurrent synaptic inhibition, also initiate their termination. During a transient, the network continually makes transitions from one equilibrium to another as a result of spontaneous firing until it is switched back to the quiescent state, i.e., after a variable period of time of noise induced transitions the transient is terminated. If the network is small, activity can terminate even without inhibition. In large networks, inhibition keeps the network sensitive to spontaneously firing cells by holding it in the neighbourhood of a critical point between active and quiescent state. PMID- 1498191 TI - The relationship between a neuronal cross-correlogram and the underlying postsynaptic current. AB - Cross-correlations between stimuli and neuronal discharges yield information about synaptic events at the investigated neuron. In this paper it is shown that the time course estimated by a cross-correlogram, the cross-correlation function (ccf), represents the input current that upon injection into the perfect integrator model evokes spike sequences that are (almost) identical to those used for estimation of the ccf. Thus, the shape of a ccf may be regarded as an estimate of the underlying postsynaptic current, if the neuron investigated behaves, at least to a first approximation, like a perfect integrator model. PMID- 1498192 TI - Thoracic and cardiovascular trauma. PMID- 1498193 TI - The diagnostic and therapeutic approach to chest trauma. AB - The diagnosis of thoracic injuries is now accomplished by a combination of time honored techniques and new modalities such as echocardiography, CT, and thoracoscopy. Operative approaches are reserved for exsanguination, significant false aneurysms, tamponade, and perforation of the main aerodigestive tracts. PMID- 1498194 TI - The multi-injured patient: the Maryland shock trauma protocol approach. AB - Thoracic trauma will continue to be a major cause of morbidity and mortality in our population. Improvement in ambulance transport systems and prehospital care has improved the salvage rate. It is hoped that earlier recognition, better understanding of the pathophysiology, and improvement in management will further reduce the number of deaths due to thoracic injuries. PMID- 1498195 TI - The cardiologist and the trauma patient: noninvasive testing. PMID- 1498196 TI - Imaging of thoracic trauma. PMID- 1498197 TI - Blunt cardiac trauma: clinical manifestations and management. AB - In conclusion, blunt cardiac trauma is the leading cause of fatalities following motor vehicle accidents. Although many of the patients with anatomic cardiac injuries die at the scene, with improved prehospital care these patients have more likelihood of surviving the first hour and presenting to an emergency room alive for definitive treatment. Prompt recognition of the injury based on the mechanism and a high index of suspicion must lead to immediate surgical intervention in order for these patients to survive. Patients with functional cardiac injuries (myocardial contusion/concussion) usually present a much less urgent scenario. They should be triaged early on the basis of admission ECG and severity of pre-existing or associated injuries to appropriately monitored units. This will allow better allocation of scarce hospital resources rather than blindly pursuing "routine" (expensive) work-ups. The sequelae of these injuries are generally nonfatal. If serious sequelae do arise in the ICU or in the OR, prompt treatment with inotropic support is usually successful. PMID- 1498198 TI - Penetrating trauma of the heart. PMID- 1498199 TI - Blunt trauma of the thoracic aorta and its branches. PMID- 1498200 TI - Spinal cord injury following surgical correction of acute aortic disruption. PMID- 1498201 TI - Injuries of the thoracic outlet. PMID- 1498202 TI - Trauma to the chest wall, lung, and major airways. PMID- 1498203 TI - Thoracic trauma and the adult respiratory distress syndrome. PMID- 1498204 TI - Injuries of the esophagus. PMID- 1498205 TI - Pediatric thoracic trauma. AB - The majority of chest injuries in children may be effectively diagnosed and treated in the emergency room area, if an organized plan is followed and a high index of suspicion for specific injuries is maintained. Unique features of pediatric anatomy and physiology require innovative adaptation to provide maximal effective resuscitation. Children in this sense are not merely "little adults." Of those few blunt and penetrating injuries that require operative management, operative techniques do not differ from those employed in adult trauma patients. PMID- 1498207 TI - [The nursing expert--integration of a new function within the structure of the nursing service]. PMID- 1498206 TI - Effects of green light on biological systems. AB - Green light (510-565 nm) constitutes a significant portion of the visible spectrum impinging on biological systems. It plays many different roles in the biochemistry, physiology and structure of plants and animals. In only a relatively small number of responses to green light is the photoreceptor known with certainty or even provisionally and in even fewer systems has the chain of events leading from perception to response been examined experimentally. This review provides a detailed view of those biological systems shown to respond to green light, an evaluation of possible photoreceptors and a review of the known and postulated mechanisms leading to the responses. PMID- 1498208 TI - [The ward nurse's key role for nursing quality]. PMID- 1498209 TI - [Nurses, returning to their profession--experiences with returning nurses]. PMID- 1498210 TI - [Health and quality circles--a participating beginning in geriatric care and nursing]. PMID- 1498211 TI - [Professional status and motivation for the choice of profession. Study on 50 nursing students and 50 commercial apprentices]. PMID- 1498212 TI - [Career patterns of nurses. Part I. Employment, functions, working time]. PMID- 1498213 TI - [Nursing science: a review]. PMID- 1498214 TI - [The situation in the nursing service and the use of nursing experts]. PMID- 1498215 TI - [Is digoxin really useful in the treatment of heart insufficiency?]. PMID- 1498216 TI - [Adolescents: healthy youngsters?]. PMID- 1498217 TI - [The use of digoxin in primary care]. AB - OBJECTIVE: A study aimed at a population attended at the Primary Health level was designed, in order to reach a greater understanding of the use of Digoxin by doctors and patients. DESIGN: A crossover observational study, carried out wholly at the Primary Care level. PATIENTS: 205 patients under long-term Digoxin treatment were studied. 94 (46%) were men and 111 (54%) women. The average age (SD) was 67 (13). MEASUREMENTS AND MAIN RESULTS: The indication was considered adequate in 62.9% of patients. The average dose (AD) of Digoxin was 0.163 mg a day (0.04): the age of the patients is not taken into account on working out the dose of Digoxin. 52 patients (25.4%) recognised they had not properly carried out the prescription. In this group the view that Digoxin was unnecessary was more common (X = 10.63; p = 0.001). The average Digoxinemia (AD) was 0.85 (0.46) ng/ml. 57% of patients had plasmatic levels below a therapeutic level. The variables related to plasmatic level were: daily dosage (r = 0.4, p = 0.001); age (r = 0.2, p = 0.001; plasmatic creatinine (r = 0.3, p = 0.001); clearing of creatinine (r = -0.4, p = 0.001) and compliance (t = 2.42, p = 0.01). The same independent variables were identified as significant in the multivariant analysis. The week-end break from dosage supposed a fall in the plasmatic levels of 67.7%. CONCLUSIONS: In spite of being a widely-used drug, the dosage of Digoxin is not adequately worked out and compliance is a long way from the optimum. Digoxinemia correlates to the dosage, renal function and compliance with the prescription. PMID- 1498218 TI - [Evaluation of a rapid technique for detecting the type A Streptococcus antigen (Test Pack Strep A)]. AB - OBJECTIVE: To test a rapid technique of Antigen Detection (TAD) of Type A Betahemolitic Streptococci (BHSA) in Acute Tonsillitis (AT), comparing it with and using as a point of reference traditional Blood Agar Cultivation (BAC). Additionally, the use of Clinical Data as a method of supposed Diagnosis was studied. DESIGN: Prospective observational study. SITE. Health Primary Care (Maspalomas Health Centre). PATIENTS AND OTHER PARTICIPANTS: 118 patients between the ages of 1 and 71 affected by AT. MEASUREMENTS AND MAIN RESULTS: There was a proportion of 13.56% BHSA in the AT of our sample, with a Confidence Interval (CI) of 95% (7.38-19.74) using the BAC; and 17.80% with a CI of 95% (10.90-24.70) using the TAD. The following values were obtained for the TAD: Sensitivity (S) of 93.75%, Specificity (Sp) of 94.12%, Positive Predictive Value (PPV) of 71.43% and Negative Predictive Value (NPV) of 98.9%. Of the clinical variables studied, only the presence/absence of Exudate and Adenopathies were linked to the presence of BHSA in the Cultivations (p less than 0.05 and p less than 0.01 respectively); with, however, inconclusive S, Sp, PPV and PNV values. CONCLUSIONS: We found insufficient correlation between clinical findings and the presence of BHSA to consider it a valid method of supposed diagnosis. There was however a statistical link between the presence of Exudate and local Adenopathies, and a positive result in the cultivation. The TAD is shown to be a rapid method, easy to use, and highly reliable for the discovery of the presence of BHSA in AT. PMID- 1498219 TI - [Follow-up of the patient with HIV infection: a hospital task?]. AB - OBJECTIVE: To assess how often patients with HIV infection abandon treatment. DESIGN: Longitudinal, prospective and observational study. SITE. Out-patient Hospital Clinic. PATIENTS AND OTHERS PARTICIPANTS: The total number of patients with HIV infection treated between September 1989 and December 1990. INTERVENTIONS: Assessment of the level of out-patient follow-up. MEASUREMENTS AND MAIN RESULTS: The rate of abandonment of out-patient follow-up was determined, with "abandonment" defined as unexplained non-attendance for at least two consecutive appointments. Its possible correlations with sex, age and HIV risk behaviour was calculated. 182 patients (143 men and 39 women) with an average age of 30.1 (ds 8.62) were surveyed. The abandonment rate for the sample as a whole was 44%, with no difference as to sex. However the abandonment rate was higher in the group of patients addicted to drugs (DDA) (69%) than in non-DDA (25%) or in ex-DDA patients (6.5%). These figures reached high statistical significance (p less than 0.01 and 0.001 respectively. CONCLUSIONS: The abandonment rate of out patient hospital follow-up by HIV-infected patients appears extremely high, especially among drug addicts (DDA). PMID- 1498220 TI - [Evaluation of the school health program for the detection of vertebral deformities]. AB - OBJECTIVE: To evaluate the prevalence of deformities of the vertebral column in the child population of a rural area; the index of false positives that diagnoses in the School Health programme generate; and the percentage of children where the diagnosis is confirmed and the treatment is then followed. DESIGN: Descriptive observational study. SITE. Public and private Schools of the Basic Areas of Sanlucar la Mayor and Olivares, and the Rehabilitation Unit of Sanlucar la Mayor Health Centre. PATIENTS AND OTHERS PARTICIPANTS: 4120 children from the first, fifth and eighth years of EGB, in 1989 and 1990. MEASUREMENTS AND MAIN RESULTS: Pathology was suspected in 5% of the children examined. 64.59% attended Rehabilitation and anomalies were confirmed in 51.85%. The level of false positives in the screening was about 48%. In 54% of the confirmed cases, Physiotherapy was indicated; in one case, Surgery; and in one case orthesis. There were no important differences as to the prevalence of Pathology among the three age groups studied. (p = 0.05). CONCLUSIONS: In spite of the small number of anomalies confirmed, their detection by means of a simple method allowed evolution to be watched and early treatment started when necessary. The low productivity of the examination was due to the high number of children that did not attend for the confirmation of the diagnosis (35%), and the false positives that the screening generated (48%). PMID- 1498221 TI - [Difficulties in carrying out the treatment as seen by the tuberculous patient]. AB - OBJECTIVE: To identify the obstacles, as seen by the patient, to adequately carrying through anti-Tuberculosis treatment. DESIGN: Crossover study. SITE. At Community level, in the city of Barcelona. MEASUREMENTS AND MAIN RESULTS: Each patient was responsible for filling in a survey at home. It was considered that a patient did not adequately carry out the treatment if he/she failed to take the medication for a period longer than three consecutive days. We discounted 66 exitus or losses and were left with 308 surveys. Out of these, the failure rate was 13.5%. The only variable statistically linked to failure was Dangerous Drug Addiction (DDA) (OR = 6.1; CI:2.3-15.8). The most common cause of failure was forgetfulness, followed by deliberate abandonment. The greatest problems in obtaining prescriptions were the opening hours or location of the dispensary. In spite of the seriousness of the illness, patients do not illness, patients do not usually give up their toxic habits. 68.8% were followed up in hospitals and only 8.8% in Primary Care Centres. CONCLUSIONS: Failure is linked to forgetfulness and deliberate abandonment. Patients have problems in obtaining prescriptions because of the opening hours and location of the prescriptions dispensary. Corrective measures should be taken for these latter problems. PMID- 1498222 TI - [An evaluation of growth tables]. AB - OBJECTIVE: To establish how suitable the growth tables we usually use are. DESIGN: A descriptive crossover study. SITE. Primary Care. Casalduch Health Centre in Castellon. PATIENTS AND OTHERS PARTICIPANTS: 120 boys and 158 girls, aged 6, who attended the Health Centre for routine School Health examinations. MEASUREMENTS AND MAIN RESULTS: The weight and height of the children was analysed. The percentil corresponding to each value was assigned in line with the growth tables in the Child Health Booklet. It was found that values higher than those expected were obtained, in both sexes and for weight and height. On comparing the proportion of girls with percentils above 5 and 75 with the theoretical proportions of 50 and 25% respectively, significant differences were obtained in all cases. CONCLUSIONS: Despite our only having studied exclusively 6 year old children in an extremely restricted geographical area, we can claim that this survey contributes to the revision and updating of the growth tables. PMID- 1498224 TI - [Organization for emergencies in primary care. Task Force of the Andalucean Society of Family and Community Medicine]. PMID- 1498223 TI - [Electrocardiogram in the hypertensive patient]. PMID- 1498225 TI - [The adoption of continuing care in the primary care teams]. PMID- 1498226 TI - [The central anticholinergic syndrome]. PMID- 1498227 TI - ["In the afternoon I get tired of talking": let's think of myasthenia gravis]. PMID- 1498228 TI - [An informative brochure, does it improve self-care of flu?]. PMID- 1498229 TI - [Are general physicians invading us?]. PMID- 1498230 TI - [Health advice]. PMID- 1498231 TI - [Pink pityriasis in primary care. Review of 46 cases]. AB - OBJECTIVE: We pretend to improve the knowledge and management of pityriasis rosea by family practitioners. DESIGN: A retrospective qualitative study by the review of the registry in a outpatient Dermatology clinic. SETTING: This work is made in the Dermatology clinic attending to San Sebastian de los Reyes population (Madrid) that's situated in the V Centenario Center. MEASUREMENTS AND MAIN RESULTS: 46 patients (28 females) were diagnosticated (mean age 25 +/- 13). Incidence was 85/100,000 hab; 12 patients were derivated urgently; 38 cases showed herald patch (82.6%). Lesions had characteristical distribution in 36 patients (78.3%); 43 cases had a clinic diagnosis (93.5%). Treatment wasn't necessary in 20 patients (43.5%). Most usual General Practitioner's presumption diagnosis was pityriasis rosea (21.7%); there was no diagnosis in 36.9%. CONCLUSIONS: We find inexperience in general practitioners about pityriasis rosea. It's necessary a correct knowledge and management of this pathology in Primary Care. PMID- 1498232 TI - [Suitability of the practice of recording only the main health problem in primary care]. AB - OBJECTIVE: To analyse if recording only the main health problem (P) can reflect in a valid way the totality of health problems (P+S) cared for and all the actions generated by a consultation. DESIGN: Using a representative sample of the patients seen at the centre over a three-month period, information on P+S was gathered, P was identified and the actions generated by each one of the problems were recorded. Health problems were codified through CIPSAP-2-D and grouping diagnoses. SITE. General Medicine service in a Primary Care Centre. PATIENTS AND OTHERS PARTICIPANTS: All the General Medical physicians at the Centre took part in the study by collecting data on the consultations established by the sampling. MAIN MEASUREMENTS AND RESULTS: Frequency and order among the first 25 P+S and P problems were compared, as was the percentage of secondary problems encountered. Out of 559 consultations examined, Diabetes, Dislepemia and an irritated? Colon stood out as under-represented. Acute infections of the Upper Respiratory Tract, Conjunctivitis and ??Queratitis were over-represented. As for the activity generated, 83.1% corresponded to P, although there was great variability among the problems according to the percentage of secondary problems according to the percentage of secondary problems. CONCLUSIONS: Recording only the main health problem can be a valid instrument for providing an initial view of problems seen. PMID- 1498233 TI - [The use of role-playing with actors and video in teaching clinical interviews to medical students]. AB - OBJECTIVE: To describe the use of the technique of role-play, using actors and recorded on video, in teaching clinical interviews to medical students; and the latters' evaluation of the methodology used. DESIGN: Prospective and observational controlled study. SITE. The Faculty of Medicine in Granada. PATIENTS AND OTHER PARTICIPANTS: The study was carried out with a group of 32 students doing the last year of Medicine. MAIN MEASUREMENTS AND RESULTS: Two actors, ten students as interviewers and two teachers were involved. The programme consisted of: a theoretical setting-out of the contents of the clinical interview; a description of the group analysis method; filming simulated interviews on video; group analysis of the material filmed; and evaluation by means of a questionnaire. The choice of interviews gave rise to no problems. The actors assumed with ease the roles they had to play. In the group work, students actively participated and made constructive contributions all the time. In the assessment the items referring to Interest, Teaching Method and Relevance and Originality were high (4.49 out of 5 points). Only that referring to documentation obtained a lower score (3.87 out of 5). CONCLUSIONS: Role-play technique, using actors and video, are excellent educational methods for teaching the clinical interview in undergraduate training. PMID- 1498234 TI - [Q fever: epidemic outbreak of the pure febrile form]. AB - OBJECTIVE: To describe an epidemic of 30 cases of Q fever, none of which had respiratory manifestations. DESIGN: Descriptive study. SITE. General medicine practices in the Billabona Health Centre, which covers the populations of Billabona and Zizurkil. PATIENTS AND OTHER PARTICIPANTS: Thirty patients, 27 men and 3 women, were diagnosed by serology as having Q fever, during and epidemic of a type of fever in Spring 1990. INTERVENTIONS: They were treated with Doxiciclin, taken orally. MAIN MEASUREMENTS AND RESULTS: A general analysis and thoracic x ray were carried out. The respiratory mechanism was not affected in any case. Transaminases were extremely high in 86% of cases. Other findings were: fever 100%, shivering 83.3%, sweating 96.6%, severe headache 86.7% and myalgia 73.4%. CONCLUSIONS: Faced with pseudoinfluenza symptoms, and in areas with high occurrence of Q fever, we should consider that we could be dealing with cases of Q fever, even when there are no respiratory manifestations. PMID- 1498235 TI - [The authors and the bibliographic references of the original articles published in the journal Atencion Primaria (1984-1990)]. AB - OBJECTIVE: The main aim of the study is to assess the developing situation of the articles published in the journal Atencion Primaria in relation to the original articles included in the same journal. There are secondary aims of describing the amount of self-quotation, the profession of the authors, their geographical distribution and their use of bibliographic references. DESIGN: A descriptive analysis of the authors and bibliographic references in the original articles. SITE. Publications and research in Primary Care. MAIN MEASUREMENTS AND RESULTS: All the original articles published in the journal Atencion Primaria during its first seven years (1984-1990). Gathering of data from the original articles (the number of authors, province of their place of work, titles, total number of references, references from Atencion Primaria, the number of self-quotations, etc.) In the seven years studied, 295 original articles have been published by 1467 authors, 44% of whom are family doctors. The average number of authors per article was 5. There are twelve Spanish provinces from which no-one has published. Altogether 4,908 bibliographic references, an average of 16.6 per article, have been used. The number of references from the journal itself rose steadily from 1% in 1984 to 11.7% in 1988, but went down to 10.3% in 1990. 52% of the bibliographic references were in Castilian and 42.6% in English. CONCLUSION: The journal Atencion Primaria is often quoted in original articles published in the same journal. The number of authors and references per original article is high but stable. PMID- 1498236 TI - [Sarcoidosis: retrospective analysis of 14 cases]. AB - OBJECTIVE: A clinical evaluation of Sarcoidosis in our environment. DESIGN: A retrospective and descriptive analysis of 14 cases encountered between 1988 and 1990. SITE. In-hospital patients studied within a catchment area of 200,000 people. PATIENTS AND OTHERS PARTICIPANTS: 13 women and 1 man ranging in age from 24 to 63 (X = 37. DS 13). All of them were confirmed histologically. MAIN MEASUREMENTS AND RESULTS: Six patients received V.O. steroid treatment. 28.5% started as Nodose Erythema, 28.5% as Respiratory Syndrome, 21% as general Toxic Syndrome. 35% were without clinical symptoms; 25% Arthralgias, 21% cough. Thoracic X-ray with bilateral hiliar adenopathies 78%; interstitial pattern 28.5%. Analytically, Monocitosis was presented in 43%; Anaemia, Hypergammaglobulinemia, rise in Transaminases in 35%; a normal ACE in 50% and raised ACE in 35%. There was a positive pulmonary Cammagraphy (Galio) in 50%. Diagnostic confirmation was made by means of transbronchial B (28%), Mediastinoscopy (14%), open Pulmonary B. (14%), Hepatic B (14%), osseous B. and Daniels (14%) and peripheric adenopathy B (14%). Pulmonary circulatory capacity (DLCO-KCO) was decreased in 3 cases. Statistic 1, 71%; 11, 14%, 111, 14%. CONCLUSIONS: Sarcoidosis is not so rare in our environment as had been thought. Factors such as a Northerly geographical situation, low temperatures, the long duration of the disease, improvement in diagnostic methods and a high level of awareness have all influenced this high number of cases found in an area of 200,000 inhabitants. The disease's clinical behaviour in our environment does not differ from that described by other spanish and foreign authors. PMID- 1498237 TI - [Pigmented basocellular epithelioma. Presentation of 7 cases]. AB - OBJECTIVE: To review the clinical, histological, evolutive and therapeutical characteristics of basal cell carcinoma and the pigmented subtype. DESIGN: Descriptive transversal study. LOCATION: Primary Care; Clinic of Dermatology in a Primary Care of Madrid. PARTICIPANTS: Seven patients (4 males, 3 females) over 60 years old with pigmented lesions and skin little pigmented. MEASUREMENTS AND MAIN RESULTS: Medical records and the histological examination were reviewed in all the cases. The clinical evolution had been the same in all the patients starting with an asymptomatic papular lesion of dark pigmentation growing slowly. Finally the lesions were transformed to a plaque or a shining nodule. Prolonged exposure to sunlight was present in five cases. All the patients were referred to the Dermatology Clinic with the presumptive diagnosis of melanoma. The lesion histological examination was diagnostic. CONCLUSIONS: It is very important the knowledge of basal cell carcinoma in Primary Care due the elevated incidence mainly among the geriatric population and the immunosupressed subjects. We must think in this type of neoplasia, doing the differential diagnosis with the other pigmented lesions. It is necessary to perform the histological examination of the suspects lesions. PMID- 1498238 TI - [Care for women: where and how]. AB - OBJECTIVE: To analyse the demand for family planning, gynecological cancer tests and pregnancy supervision in an area with no public resources devoted specifically to these questions. To evaluate users' level of satisfaction and their readiness or otherwise to be visited at the Health Centre (HC), with a view to planning out a specific programme. DESIGN: Descriptive study. SITE. Health Centre at Castelldefels. (Barcelona). PATIENTS AND OTHER PARTICIPANTS: Random stratified sample of 595 women over 14, living within the centre's catchment area. The age distribution was selected in line with the town's population pyramid. MAIN MEASUREMENTS AND RESULTS: We undertook a self-administered, anonymous survey of 437 women. 4.9% of those sexually active between the ages of 14 and 20 and 13.2% of women aged between 21 and 45 use no contraceptive method. The greater attendance at private rather than public centres for contraception (73% as against 23.8/1000 p less than 0.001) and for regular check-ups (63.8% as against 32.1/1000 p less than 0.001) was notable. But for pregnancy care it was the other way round (29.3% as against 61.2/1000 p less than 0.001). 64.1% have regular check-ups; 48.8% annually. A higher level of satisfaction is shown by women seen at private (95.2%) than at public centres (75.1/1000 p = 0.0159). 68.9% would use a special care services for women if offered by the HC. CONCLUSIONS: Existing services offer scant cover to sections of the population more at risk and tend to make everything a medical problem. The public centres give little user-satisfaction. The Primary Care teams could cover these deficiencies with their services and would be welcome by the public. PMID- 1498239 TI - [Which statistical method? Guide to choose the most appropriate statistical test for the hypothesis contrast]. PMID- 1498240 TI - [Diagnostic and therapeutic criteria of acute respiratory infection]. PMID- 1498241 TI - [Community participation: a necessary review]. PMID- 1498242 TI - [Correct diagnosis and obtainable objectives in a program for chronic air-flow obstruction in primary health care]. PMID- 1498243 TI - [Pulmonary toxicity of amiodarone]. PMID- 1498244 TI - [Prevalence of markers against hepatitis B and C virus among hospital female personnel in childbearing age]. PMID- 1498245 TI - [Chronic subdural hematoma in pediatric domiciliary notice]. PMID- 1498246 TI - [Pernicious anemia in primary care. Report of a case]. PMID- 1498247 TI - Solvent damping of internal processes in myoglobin studied by specific heat spectroscopy and flash photolysis. AB - We address the question of dynamic coupling between protein and solvent by comparing the enthalpy relaxation of the solvent (75% v/v glycerol-water) to internal ligand binding in myoglobin. When the solvent relaxation is slow compared to intramolecular events we observe decoupling of protein motions from the solvent. In the opposite limit there is a significant contribution of the solvent to internal friction. The solvent enhances the apparent activation energy of transitions in myoglobin. This result is discussed in terms of a generalized Kramer's law involving a dynamic friction coefficient. PMID- 1498248 TI - Reaction rate enhancement by surface diffusion of adsorbates. AB - Ligands can be captured by a surface target through either direct bulk diffusion or surface diffusion following reversible adsorption to the surface. We have solved a steady state boundary value problem for a perfect sink disk target in the surface, taking into account bulk and surface diffusion coefficients D and Ds and adsorption/desorption kinetic rate constants ka and kd at non-target regions. Solutions have been successfully found by numerical computation. The results show that the rate of capture from the surface depends non-linearly on Ds, D, ka, kd and geometrical dimensions. In particular, we demonstrate that not only is the non-target region equilibrium constant Keq (= ka/kd) important in determining the rate of capture from the surface, but so are the kinetic rate constants ka and kd separately. In all cases, the surface adsorption/diffusion combination enhances the total rate of capture. The results should be useful for predicting reaction rates of biological membrane bound receptor clusters and substrate-immobilized enzymes. PMID- 1498249 TI - Isoelectric point of an ion-penetrable membrane. AB - The surface potential of an ion-penetrable planar membrane is calculated for the case in which acidic and basic groups are present in the membrane. It is found that when both acidic and basic groups are not uniformly distributed in the direction normal to the membrane, the isoelectric point (the pH value at which the surface potential becomes zero) of the membrane varies with the electrolyte concentration, whereas if both groups are uniformly distributed, the isoelectric point is independent of the electrolyte concentration. As a simple example, we treat a membrane consisting of two layers, in which acidic groups are distributed in the outer layer and basic groups are in the inner layer. Simple equations determining the membrane surface potential as a function of pH and electrolyte concentration and the dependence of the isoelectric point on the electrolyte concentration are presented. PMID- 1498250 TI - Solvation effects upon the thermodynamic substrate activity; correlation with the kinetics of enzyme catalyzed reactions. I. Effects of added reagents such as methanol upon alpha-chymotrypsin. AB - Solvents, detergents, etc., have often been added to the medium to study the kinetics of enzyme action and for binding studies. They have been employed for diverse reasons such as solubilization of substrates or to stabilize an enzyme that was originally membrane bound. Thermodynamic considerations dictate that any added substance, such as methanol, which is present in significant quantity must affect the thermodynamic activities of the enzyme, enzyme-substrate complex, substrate and any other intermediates although cancellation effects may occur in this regard. The influence upon substrate activities is the only one that is easily experimentally accessible. These effects are shown, from the data of Bernard and Laidler, to be large in the case of the alpha-chymotrypsin catalyzed hydrolysis of methylhydrocinnamate. The variation of the Michaelis-Menten constant is quantitatively explainable in terms of the alteration of the thermodynamic activity of the substrate by methanol. PMID- 1498251 TI - Solvation effects upon the thermodynamic substrate activity; correlation with the kinetics of enzyme catalyzed reactions. II. More complex interactions of alpha chymotrypsin with dioxane and acetone which are also competitive inhibitors. AB - It is shown that the effects of the addition of various amounts of dioxane and acetone (solvent modifiers) upon the alpha-chymotrypsin-catalyzed hydrolysis of methylhippurate can be explained in terms of three factors. (A) The effects of the above modifiers on the chemical potential of the substrate. (B) The solvent modifiers dioxane and acetone also act as classical competitive inhibitors. The means of sorting out these contributions is presented. (C) The alterations of the chemical potentials or for free energies of the enzyme, enzyme-substrate complex, and/or other intermediates by the added modifiers appear to cancel out with the substrate used here. PMID- 1498252 TI - The transcriptional control of TGF-beta in human osteoblast-like cells is distinct from that of IL-1 beta. AB - Transforming growth factor beta (TGF-beta) and interleukin 1 (IL-1) are among the most potent osteotropic cytokines. The expression of mRNA for both TGF-beta and IL-1 beta was studied in human osteoblast-like cells in vitro. These cells constitutively expressed TGF-beta but not IL-1 beta mRNA. Treatment of the cells with the systemic hormones 1,25-dihydroxyvitamin D3 [1,25-(OH)2D3] (10(-8) M) and parathyroid hormone (10(-7) M) induced an increase in TGF-beta mRNA but failed to stimulate the production of IL-1-beta mRNA. Retinoic acid (10(-8) M) had no effect on either mRNA species. The cytokines IL-1 alpha (200 pg/ml), tumour necrosis factor alpha (TNF-alpha) (17 ng/ml) and bacterial lipopolysaccharide (LPS) (500 ng/ml) stimulated the production of IL-1 beta mRNA after 6-8 hours. This was followed by an increase in protein production after 24 hours. In contrast, the production of TGF-beta mRNA remained constant after treatment with these agents. Treatment of the cells with hydrocortisone (10(-8) M) resulted in the suppression of both TGF-beta and IL-1 beta mRNA. However, when the stimulating agent 1,25-(OH)2D3 was added in conjunction with hydrocortisone the mRNA expression of TGF-beta mRNA returned to 70% of the stimulated level. In contrast, the addition of the stimulatory agent IL-1 alpha to hydrocortisone treated cells resulted in no increase in IL-1 beta mRNA. In-situ hybridization demonstrated both TGF-beta and IL-1 beta mRNA at the cellular level.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1498253 TI - Blood-derived macrophages produce IL-1, but not TNF-alpha, after infection with HIV-1 isolates from patients at different stages of disease. AB - Interleukin 1 (IL-1) and tumor necrosis factor alpha (TNF-alpha) are not constitutively produced by human mononuclear phagocytes. In the present study we have investigated the production of these cytokines in human blood-derived macrophages (BDM) after infection with 16 primary HIV-1 blood isolates obtained from individuals at different stages of disease. In addition, we monitored the replicative capacity of these primary isolates in blood-derived macrophages over a 3-month period. Production of IL-1 alpha was detected in two cultures, IL-beta was positive in two other cultures, and both IL-1 alpha and IL-beta were present in three additional macrophage cultures. IL-1 alpha production was also detected in BDMs infected with the laboratory strain HIV-1 IIIB. In contrast, TNF-alpha was not found in any of the culture supernatants tested. All primary HIV-1 isolates used in these experiments were able to infect BDM productively irrespective of the clinical stage of the patients at the time of virus isolation. The production of IL-1 was mostly found in chronically infected cultures displaying low levels of HIV-1 replication. These results indicate that macrophages tropism is a general feature of all HIV-1 isolates. Furthermore, release of IL-1 by mononuclear phagocytes upon HIV-1 infection may contribute to the pathogenesis of HIV-1 related diseases. PMID- 1498254 TI - Cytometrically detected specific binding of interleukin 2 to cells. AB - We have developed a new technique for detecting binding of interleukin 2 (IL-2) to cells. This technique involves incubating the cells with IL-2 and then analysing the cell surface with specific anti-IL-2 antibodies and flow cytometry. This binding was only detected on tumor cells that possessed the p55 subunit of the IL-2 receptor. The role of p55 was ascertained by inhibition of the binding with a monoclonal antibody to p55. Although p55 is necessary for cytometrically detected IL-2 binding, further studies demonstrated that p55 is not sufficient. Thus, cytometrically-detected binding is likely to involved the contribution of other IL-2 surface receptors. Interleukin-2 binding to peripheral blood T lymphocytes and to a non-transformed T-cell clone was also detected cytometrically and it was shown that this binding is regulated by the activation status of the cells. Whereas IL-2 binding to quiescent T cells could not be detected, upon activation abundant binding was seen. The functional consequences of this type of cellular binding were studied. Interleukin-2 binding to cells during a short pulse was shown to have significant long-term consequences both for T-cell proliferation and for the enhancement of major histocompatibility complex (MHC)-non-restricted cytotoxicity. PMID- 1498255 TI - Oxidative tryptophan metabolism in renal allograft recipients: increased kynurenine synthesis is associated with inflammation and OKT3 therapy. AB - Serum concentrations of tryptophan (TRP) and kynurenine (KYN) were determined in renal allograft recipients (RAR) as an index of interferon-gamma-induced, indoleamine-dioxygenase-catalysed TRP degradation. Serum TRP and KYN in RAR during periods of stable graft function were typically within the normal range, however, the median values for serum KYN demonstrated significant increases 5-7 days prior to biopsy-confirmed acute rejection (1.6-fold, P less than 0.01) and on the day of biopsy (1.7-fold, P less than 0.001). Serum KYN was also markedly elevated in patients who contracted viral or Gram-negative bacterial infections in the absence of graft rejection. Serum KYN was not correlated with serum creatinine in RAR nor were serum TRP or KYN affected by antirejection therapy with high dose steroids. Retrospective analysis of intra-patient changes in serum KYN demonstrated that KYN monitoring was a useful adjunct to serum creatinine in the early detection of first acute rejection episodes. The first course of OKT3 therapy was associated with low serum TRP and significant increases in serum KYN (two- to three-fold) following the first three doses. The time course of these abnormalities corresponded to that over which many of the side effects of the OKT3 'first dose reaction' have been reported to occur. Significant changes in serum KYN were not observed in patients receiving repeat courses of OKT3 therapy. Significant decreases in serum TRP and significant increases in serum KYN were both prevalent and frequent in RAR during the first two postoperative months.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1498256 TI - Comparison of the cytostatic and cytolytic activity of tumor necrosis factor alpha and interleukin 1 alpha in human malignant cell lines. AB - The cytokines tumor necrosis factor-alpha (TNF-alpha) and interleukin 1 alpha (IL 1 alpha) share many properties, including in-vitro cytotoxicity. Because cytotoxicity can result from either cytolytic or cytostatic activity, and because differentiating between these activities may have clinical relevance, we determined the cytostatic and cytolytic activity of TNF-alpha and IL-1 alpha for the human cell lines ME-180, SiHa (cervical carcinomas) and A375 (melanoma). Results of these analyses showed that IL-1 alpha mediated cytostatic activity only for A375 cells. IL-1 alpha was not cytolytic in the presence or absence of protein synthesis inhibitors. TNF-alpha was cytostatic for A375 and ME-180 cells, and although TNF-alpha was not cytolytic in the absence of protein synthesis inhibitors, it was cytolytic in the presence of protein synthesis inhibitors. These results suggest that the difference between the cytolytic and cytostatic activities of IL-1 alpha and TNF-alpha may have therapeutic implications for the use of these biological response modifiers in the treatment of gynecological malignancies. PMID- 1498257 TI - Interleukin 2 treatment of Staphylococcus aureus mastitis. AB - A study was conducted in dairy cows to evaluate the efficacy of recombinant bovine interleukin 2 (rBoIL-2) as an adjunct to antibiotic therapy in Staphylococcus aureus mastitis. In normal, non-mastitic cows, intramammary infusion of rBoIL-2 caused a tenfold increase in somatic cell counts (SCC) in milk. Co-administration of 2 mg of rBoIL-2 and sodium cephapirin in cows with established S. aureus mastitis decreased SCC and shedding of S. aureus compared with values from cows that were given only sodium cephapirin or 10 mg rBoIL-2 with sodium cephapirin. Cows in the 2 mg rBoIL-2 group cleared the infection earlier and at 2 weeks after treatment had not relapsed with staphylococcal mastitis. These data suggest that rBoIL-2 may be useful as an immunotherapeutic agent in controlling mastitis. PMID- 1498258 TI - Induction of swelling, synovial hyperplasia and cartilage proteoglycan loss upon intra-articular injection of transforming growth factor beta-2 in the rabbit. AB - Transforming growth factor beta (TGF-beta) is a multifunctional homodimeric polypeptide with potent actions upon many target cells, including those of mesenchymal and haemopoietic lineage. The recent reports of high levels of the cytokine in rheumatoid synovium and synovial fluid, prompted this study into the effect of intra-articular injection of TGF beta-2 into rabbit knee-joints. Four daily injections of 1 microgram caused swelling, probably as a consequence of prostaglandin E2 production, synovial fibroblastic hyperplasia and a striking loss of femoral condyle proteoglycan. Using the polymerase chain reaction, no evidence could be obtained for the induction of interleukin-1 alpha gene expression in either synovial tissue or synovial fluid cells. These findings suggest that the TGF-beta present in the rheumatoid joint may contribute directly to the pathogenesis of rheumatoid arthritis. PMID- 1498259 TI - Direct stimulation of cytokines (IL-1 beta, TNF-alpha, IL-6, IL-2, IFN-gamma and GM-CSF) in whole blood. I. Comparison with isolated PBMC stimulation. AB - Production of interleukin 1 beta (IL-1 beta), interleukin 6 (IL-6), tumor necrosis factor alpha (TNF-alpha), interleukin 2 (IL-2), interferon gamma (IFN gamma) and granulocyte-macrophage colony-stimulating factor (GM-CSF) after stimulation by lipopolysaccharide (LPS) and phytohemagglutinin (PHA) was studied in 1/10 diluted whole blood (WB) culture and in peripheral blood mononuclear cell (PBMC) culture. Cytokines IL-1 beta, TNF-alpha and IL-6 are preferentially stimulated by LPS whereas IL-2, IFN-gamma and GM-CSF are stimulated by PHA. Combination of 5 micrograms/ml PHA and 25 micrograms/ml LPS gave the most reliable production of the six cytokines studied. IL-1 beta, TNF-alpha and IL-6 represent a homogeneous group of early-produced cytokines positively correlated among themselves and with the number of monocytes in the culture (LeuM3). Furthermore, IL-1 beta was negatively correlated with the number of T8 lymphocytes. IL-2, IFN-gamma and GM-CSF represent a group of late-produced cytokines. Kinetics and production levels of IL-6 and GM-CSF are similar in WB and PBMC cultures. In contrast, production levels of TNF-alpha and IFN-gamma are higher in WB than in PBMC whereas production levels of IL-6 and IL-2 are lower in WB than in PBMC. Individual variation in responses to PHA + LPS was always higher in PBMC cultures than in WB cultures. The capacity of cytokine production in relation to the number of mononuclear cells is higher in WB, or in PBMC having the same mononuclear cell concentration as WB, than in conventional cultures of concentrated PBMC (10(6)/ml). Because it mimics the natural environment, diluted WB culture may be the most appropriate milieu in which to study cytokine production in vitro. PMID- 1498260 TI - Anti-tumor cytotoxic potential and effect on human bone marrow GM-CFU of human LAK cells generated in response to various cytokines. AB - The effects of various recombinant cytokines i.e. IL-1 alpha, IL-3, IL-4, IL-6, IFN-gamma, TNF-alpha and GM-CSF used either alone or in combination with IL-2, were investigated in this study. First, their capacity to induce killer cells from human PBL was examined by evaluating the degree of killing of human NK sensitive K562 or NK-resistant Daudi cells. Second the effects of these cytokines, LAK cells (at 1/1, 2/1, 4/1 ratio LAK effectors/bone marrow cell targets) and of the supernatants from washed killer cell cultures, were examined on the colony forming ability of human bone marrow for GM-CFU in vitro. Various degrees of NK activity against K562 was observed in PBL stimulated with the cytokines, whereas LAK activity was found only with IL-2 alone. Culture of PBL with IL-2 + IL-1 alpha or IL-2 + IL-6 or IL-2 + GM-CSF resulted in the highest LAK killing. However, addition of TNF-alpha, or IFN-gamma to IL-2 in cultures resulted in a significant suppression of LAK cell activity. Addition of IL-1 alpha, IL-2, IL-3, and IL-4 to BM cultures had little or no effect on day 14 GM CFU, whereas addition of IL-6 and GM-CSF resulted in a stimulatory effect. LAK cells induced with IL-2 alone had no significant suppressive effects on GM CFU.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1498261 TI - Augmentation of cytostatic effect of recombinant human lymphotoxin and involvement of glutathione redox cycle. AB - The effect of buthionine sulfoximine (BSO), an inhibitor of glutathione biosynthesis, in combined use with a nitrosourea derivative, ACNU, on the cytostatic effect of recombinant human lymphotoxin (rhLT) was studied in vitro. The simultaneous addition of 0.02 mM or 0.5 mM BSO and rhLT slightly augmented the inhibition of Meth A tumor cell proliferation. Similar tendency was observed when the target cells were treated with 0.02 mM or 0.5 mM BSO for 24 hr prior to the addition of rhLT. A marked augmentation of the antiproliferative effect was obtained when the target cells were treated in vitro with 0.005 mM or 0.02 mM BSO prior to the addition of 0.02 mM or 0.1 mM BSO and rhLT. The addition of ACNU simultaneously with rhLT to BSO-treated cells also augmented the antiproliferative effect. These results suggest that the glutathione redox cycle is closely related to the mechanism of LT-induced cytotoxicity. PMID- 1498262 TI - IL-6 mRNA expression in CD25 positive malignant lymphomas. AB - We recently demonstrated that IL-2 is produced by reactive T cells in CD25 positive malignant lymphomas (ML). Using in situ hybridization, we investigated IL-6 mRNA expression in these CD25-positive ML. The ML tested included 9 anaplastic large cell lymphomas and 3 B-diffuse large cell lymphomas. Five CD25 negative ML were studied as controls. We show that IL-6 producing cells are present in all these ML. The density of positive cells was heterogeneous from case to case. However 3 cases of CD25-positive ML showed a dramatically higher density of IL-6 producing cells (70, 50, 43 producing cells per 10,000 cells, respectively) as compared to the other 9 cases of CD25-positive ML (mean 6.03 +/- 2.1 per 10,000). Morphological and topographical data suggested that several types of cells including fibroblasts, lymphocytes, macrophages and endothelial cells may synthesize IL-6. A combination of immunohistochemistry and in situ hybridization showed that reactive T cells and endothelial cells express the IL-6 gene whereas CD30-positive ML cells do not express this gene. Previous studies showed that IL-6 was capable to induce IL-2 receptor expression as well as production of IL-2 and stimulation of lymphomatous cells growth. Our present results indicate that the paracrine production of this cytokine may play a role in the proliferation of malignant lymphomas. PMID- 1498263 TI - Circadian rhythm of soluble interleukin-2 receptor in healthy individuals. AB - The cytokine levels of soluble interleukin-2 receptor (sIL-2R), interleukin-6 (IL 6) and tumor-necrosis-factor alpha (TNF-alpha) were studied in 12 healthy volunteers at 11 different times of day. TNF-alpha levels were below the detection limit, and IL-6 levels were at baseline values of the respective assay used. Interindividual variations were found for the plasma levels of sIL-2R (179 524 U/ml). Shedded IL-2 receptors displayed a pronounced circadian phase dependency (p less than 0.0001) with a peak value at 12:29 h and a trough at 4:14 h when a complex cosine function (period lengths: 24 h plus 12 h) was fitted to the data. These findings may be of importance when using sIL-2R as a diagnostic tool as well as in controlling efficacy of drug treatment. PMID- 1498264 TI - Drugs and the liver. Part III: Ageing of the liver and the metabolism of drugs. AB - The clearance of many drugs by the liver is reduced in the elderly, and this accounts, at least in part, for the greater frequency of adverse drug reactions in this population. Ageing in experimental animals is accompanied by a decline in the activities of certain microsomal monooxygenase enzymes; this has been said to be the reason for decreased drug elimination. However, recent data suggests that this is probably not the case in humans. Reduced size and blood flow are important features of the ageing liver, and probably account for most of the age related changes in drug metabolism. Major decrements in hepatic function do occur in frail elderly individuals, although the mechanisms underlying this are at present unclear. Future studies of drug metabolism and ageing must carefully define patient groups to allow full interpretation of data. PMID- 1498265 TI - Effect of indomethacin on the pharmacokinetics of methotrexate in rabbits. AB - The interaction between indomethacin (IND) and methotrexate (MTX) was investigated in rabbits. The study was designed so as to evaluate the effect of IND (1 mg h-1) during a continuous MTX infusion (1 x 2 mg kg-1) over 240 min. IND was injected i.v. at hourly intervals after a steady state MTX concentration had been established. Plasma MTX concentration before and after IND did not differ significantly (p greater than 0.05). The elimination half-life (t1/2 beta) calculated during the washout interval (mean +/- SD) was 47 x 4 +/- 21 x 5 min which is close to that calculated in a reference group of rabbits. This excludes the possibility of delayed elimination as responsible for this toxicity. The toxicity of this combination was confirmed despite the absence of significant pharmacokinetic changes. It is possible that the toxic interaction was caused by enhanced cytotoxic effect of MTX. PMID- 1498266 TI - Effect of food and relative bioavailability following single doses of diclofenac 150 mg hydrogel bead (HGB) capsules in healthy humans. AB - The effect of food on the bioavailability of diclofenac from a 150 mg diclofenac hydrogel bead (HGB) capsule was evaluated in 12 healthy male subjects in a fed and fasted state. Additionally, the fasting bioavailability of diclofenac from a 150 mg diclofenac HGB capsule relative to diclofenac sodium in buffered aqueous solution was evaluated in these same 12 subjects. The study was designed as an open-label, randomized, single-dose, 3 x 3 Latin-square crossover trial balanced for residual effects. A 2-week washout period was maintained between treatments. Blood samples were collected at frequent intervals over a 24-h period with plasma being separated and analyzed for diclofenac using a validated HPLC method. The administration of the 150 mg diclofenac HGB capsule dose within 30 min following a standardized breakfast minimally affected the bioavailability of diclofenac relative to administration under fasted conditions (7 per cent decrease in AUC(0 24), p greater than 0.05). There was, however, a 38 per cent decrease (p less than 0.05) in the Cmax and a three-fold increase (p less than 0.05) in Tmax for the fed HGB capsule administration. Under fasted conditions, significant differences in mean pharmacokinetic parameters were found between the 150 mg diclofenac HGB capsule and diclofenac sodium in buffered aqueous solution. The extent of availability of diclofenac from the HGB capsule was only 59 per cent relative to that from the solution (p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1498267 TI - Pharmacokinetics of ibuprofen enantiomers after single and repeated doses in man. AB - The pharmacokinetic parameters of ibuprofen enantiomers after a single 600 mg dose and repeated 3 x 400 mg doses of Nurofen were determined in 12 healthy volunteers. Terminal half-lives were similar for both enantiomers, but plasma levels of S-ibuprofen were higher than those of R-ibuprofen, due to the chiral inversion and differences in distribution and metabolism. Comparison of maximal concentrations and areas under the concentration vs time curves between the first and last doses for each enantiomer indicated linear pharmacokinetics with no time dependency. A large inter-individual variability in the ratio of S- to R ibuprofen average concentrations at steady-state was observed (mean +/- SD 1.89 +/- 0.89) and probably accounts for the known lack of correlation between racemic ibuprofen concentrations and therapeutic efficacy. PMID- 1498268 TI - Plasma disposition and hemodynamic effects of a single oral dose of isosorbide dinitrate in human males and females. AB - The goal of the present work was to determine the plasma disposition and hemodynamic effects of isosorbide dinitrate (ISDN) in human males and females. Fourteen healthy human volunteers took part in the study; seven males, 21.7 +/- 2.5 y (SD), and seven females, 20.7 +/- 3.4 y. Measurements of forearm blood flow (FBF), vascular conductance (FVC), and venous capacitance (Cv) were obtained by venous occlusion plethysmography, whereas blood pressure was measured by automatic sphygmomanometry. Blood samples were taken through a catheter placed in the antecubital vein at 0, 15, 30, 45, 60, 90, 120, 360, 480, 720, and 1440 min following a single 10 mg oral dose of ISDN. Plasma concentrations of ISDN and its mononitrate metabolites, isosorbide-2-mononitrate (2-ISMN) and isosorbide-5 mononitrate (5-ISMN), were determined by large bore capillary column gas-liquid chromatography. Hemodynamic measurements were made at corresponding experimental times up to 480 min. No differences were observed in the disposition of ISDN, 2 ISMN or 5-ISMN between the male and female volunteers. In addition, the plasma concentrations of ISDN and its mononitrate metabolites did not consistently correlate with the hemodynamic changes of the individual subjects. Diastolic blood pressure was significantly decreased for a 0.5 h period starting at 30 min, which was the time at which plasma ISDN concentrations peaked, and which preceded the time when the plasma concentrations of 2-ISMN and 5-ISMN were maximal. These observations indicate that, for a single 10 mg oral dose of ISDN, there were no gender-dependent differences in the plasma disposition of the parent drug or its mononitrate metabolites, and the vascular changes responsible for the decrease in diastolic blood pressure in these volunteers occurred in vascular beds other than those of skeletal muscle as represented by forearm blood flow. PMID- 1498269 TI - Pharmacokinetics/pharmacodynamics of labetalol in three pregnant ewes using high performance liquid chromatography. PMID- 1498270 TI - Enantioselective versus non-enantioselective assays in comparative bioavailability studies with racemic drugs. PMID- 1498271 TI - 1991 Homer Smith Award recipient. Heini Murer. PMID- 1498272 TI - Homer Smith Award. Cellular mechanisms in proximal tubular Pi reabsorption: some answers and more questions. AB - Inorganic phosphate (Pi) is reabsorbed mainly in the proximal tubule, by a second active Na-dependent transport mechanism. Na/Pi cotransport with a stoichiometry exceeding unity mediates uphill flux across the brush border membrane; at the basolateral cell surface, two separate transport systems are involved in equilibrating Pi fluxes. The protein structure of a rabbit renal cortex Na/Pi cotransport system has been identified recently by expression cloning. The regulation of tubular Pi reabsorption involves mainly alterations in the transport rate of the brush border membrane Na/Pi cotransport system. The regulation of this transport step by either parathyroid hormone (PTH) or Pi deprivation is discussed, mostly on the basis of observations made with a tissue culture model, OK cells derived from opossum kidney. In this model, PTH may use a dual signaling cascade to inhibit apical Na/Pi cotransport (phospholipase C/protein kinase C and adenylate cyclase/protein kinase A). PTH action on Na/Pi cotransport may involve an endocytosis mechanism. For the regulation of apical Na/Pi cotransport by chronic Pi deprivation, the number of "Na/Pi cotransporter" molecules seems to be unaffected; the increased transport rate is apparently related to an "unknown" stimulating event at the membrane level (e.g., a change in the lipid microenvironment), which itself is under the control of protein synthesis/degradation. The availability of new tools (cloning of Na/Pi cotransporter(s) and of PTH receptor(s)) will allow us to enter into a new era in the study of cellular mechanisms involved in proximal tubular Pi reabsorption. PMID- 1498273 TI - Diagnosing Mozart's mortal illness: an exercise in cranio-nephrology. PMID- 1498274 TI - Did Mozart die of kidney disease? A review from the bicentennial of his death. AB - There has been a tremendous interest in the circumstances of Mozart's death. Theories of head trauma, poisoning, heart disease, and most prominently, renal failure have all appeared recently in scholarly musicology publications, the lay press, and the medical literature. The purpose of this article is to present the evidence behind each of these theories. Although this review cannot be considered comprehensive, with the overview provided, it will be shown that few conclusions can be drawn. PMID- 1498275 TI - Experimental tests of three-dimensional model of urinary concentrating mechanism. AB - Recently, a new model of the urinary concentrating process has been proposed that takes into account the three-dimensional architecture of the renal medulla. Under the assumptions of the model, computer simulations predicted significant axial osmolality gradients in the inner medulla without active transport by the inner medullary loop of Henle. Two of the model assumptions (which constitute hypotheses for this study) were: (1) the osmotic water permeability of the initial part of the inner medullary collecting duct (initial IMCD) is very low even in the presence of vasopressin; and (2) there is significant lateral separation of structures such that thin descending limbs are far from the collecting ducts at the same inner medullary level. The first hypothesis was addressed by perfusing rat initial IMCD segments in vitro and measuring osmotic water permeability. With the osmotic gradient oriented as predicted by the model (lumen greater than bath), vasopressin increased the osmotic water permeability from 286 to 852 microns/s. Three additional series of experiments confirmed the high water permeability in the presence of vasopressin. The second hypothesis was addressed by morphometric analysis of histologic cross-sections of the rat renal medulla. Mean distances of descending limbs to the nearest adjacent collecting duct were very small throughout the inner medulla (less than 6 microns) and substantially less than in the outer medulla (28 microns). It was concluded that the data are inconsistent with both hypotheses and therefore do not support the feasibility of the "three-dimensional" model of the renal inner medulla. The axial distributions of loops of Henle and collecting ducts in the rat renal medulla are also reported. PMID- 1498276 TI - Urinary concentrating ability in patients with Jk(a-b-) blood type who lack carrier-mediated urea transport. AB - Water homeostasis is regulated in large part by the proper operation of the urinary concentrating mechanism. In the renal inner medulla, urea recycling from the inner medullary collecting duct to the inner medullary interstitium is thought to be essential for the production of a concentrated urine; however, it has not been possible to test this hypothesis in humans. Recently, a unique combination of genetic abnormalities has been described: absence of Kidd blood group antigens and absence of carrier-mediated urea transport in erythrocytes. Because animal studies indicate a similarity between urea transport in red blood cells and the nephron, it was postulated that patients without the Kidd antigen might lack facilitated urea transport in their kidneys. Hence, their ability to concentrate urine maximally was measured. Current models of nephron function would predict that in the complete absence of urea transport, the maximal concentrating ability would be around 800 to 900 mosM/kg H2O. Two homozygous patients had a moderate decrease in maximal concentrating ability (UosM,max = 819 mosM/kg H2O); a heterozygote also had some limitation. These studies raise the possibility that the erythrocyte urea transporter and the kidney urea transporter are encoded by a single gene (detected by the mutational loss of the Kidd antigen) and that a lack of facilitated urea transport impairs urea recycling in the kidney and, hence, maximal urinary concentrating ability. PMID- 1498277 TI - Age-related changes in glomerular volume and hydroxyproline content in rat and human. AB - Total 4-hydroxyproline content and volume were measured in the same sample of microdissected glomeruli obtained fro rat and human outer or inner cortex. Glomerular volume was determined by computer-assisted image analysis, and 4 hydroxyproline was measured by a highly sensitive gas-liquid chromatographic method. Results were expressed as weight of basement membrane material by comparison with the amount of 4-hydroxyproline in purified basement membrane/mesangial matrix preparations. Microanalyses were possible in samples containing as few as eight human glomeruli. Rat glomerular size increased sevenfold between 5 wk and 2 yr of age, with volume being consistently 36 to 45% greater in inner than in outer cortex glomeruli. Basement membrane material content per glomerulus markedly increased with age (12-fold); however, when expressed per unit volume, this change was greatly reduced (2-fold). Expressed per volume, inner and outer cortex glomerular content of basement membrane material was always similar, regardless of age. Therefore, a greater glomerular size, in itself, does not accelerate the rate of basement membrane material deposition. Glomerular size distributions (measured by skewness and kurtosis) did not change, indicating that, although glomerular volume increases with age, aging does not appear to cause the emergence of distinct glomerular populations within an age group. Basement membrane material accumulation is probably a generalized change. Human glomeruli increased sevenfold in size from infancy to adulthood and then declined during senescence. Contrary to that in the rat, glomerular basement membrane material content appeared to closely follow size changes, thus, varying little from infancy to senescence if expressed per unit of glomerular volume. PMID- 1498278 TI - Altered synthesis and intracellular transport of proteoglycans by cyst-derived cells from human polycystic kidneys. AB - Employing in vitro pulse-chase techniques, we investigated the de novo synthesis and the kinetics of intracellular transport and extracellular matrix incorporation of proteoglycans (PG) by normal human renal epithelial cell and by epithelial cells isolated from cysts of autosomal dominant kidneys (ADPKD). Cell monolayers were pulsed either with (3H)leucine for 15 min and chased for seven intervals between 15 and 270 min or with (35S)sulfate for 150 min and chased for a single interval of 120 min. Total proteins and PG were isolated from cell, media, and matrix fractions and characterized by Sepharose CL-6B and DEAE Sephacel chromatographies. ADPKD and NK cells synthesized comparable amounts of total proteins; however, the de novo synthesis of PG by ADPKD cells was significantly reduced. ADPKD versus NK cells exhibited a substantial delay in the cellular transport and extracellular release of de novo synthesized PG, indicating an impairment at the level of the Golgi complex and/or secretory vacuoles. PG synthesized by ADPKD versus NK cells had decreased charge density characteristics, probably due to a posttranslational defect in the sulfation of the PG glycosaminoglycan chains. ADPKD versus NK cells synthesized PG of higher molecular weight and had an increased proportion of chondroitin sulfate PG versus heparan sulfate PG. Collectively, these findings suggest a defect in the synthesis and intracellular transport of sulfated PG in human ADPKD cells. PMID- 1498279 TI - Renal transplantation in the first year of life: the treatment of choice for infants with end-stage renal disease. AB - The treatment of choice for end-stage renal failure within the first year of life is controversial. Between September 1970 and February 1991, we performed 28 kidney transplants (27 primary, 1 retransplant, 23 living donor, 5 cadaver) in infants less than 1 yr of age (mean, 7 +/- 2 months; range, 6 wk to 12 months). The 1-yr patient survival rate for living donor recipients was 100% versus 20% for cadaver recipients (P = 0.0001). The 1-yr graft survival rate for living donor recipients was 96% versus 20% for cadaver recipients (P = 0.001). The 1-yr patient survival rate for cyclosporin A (CSA) recipients (N = 12) was 100% versus 75% for non-CSA recipients (P = 0.03). The 1-yr graft survival rate for CSA recipients was 92% versus 75% for non-CSA recipients (P = 0.08). There was no difference in the number of rejection episodes or serum creatinine levels in CSA versus non-CSA recipients. Compared with pretransplant values, the mean posttransplant standard deviation scores (SDS) for height (N = 18), weight (N = 22), and head circumference (N = 8) improved: height SDS from -1.9 to -1.5 (not significant); weight SDS from -2.5 to 0.6 (P less than 0.0005); head circumference SDS from -2.0 to -0.7 (P = 0.01). Because no other renal replacement therapy can match these results, we conclude that renal transplantation is the treatment of choice for infants with end-stage renal failure. PMID- 1498280 TI - Does human lymphocyte antigen matching improve the outcome in pediatric renal transplants? AB - Adult studies have shown a high renal graft survival if the donor and recipient match for each antigen of the human lymphocyte antigen (HLA)-A, B and DR loci (six-antigen match). The 4 yr of data from the North American Pediatric Renal Transplant Cooperative Study Registry show a statistically beneficial effect of DR matching for cadaver graft outcome. No antigen matching clearly has a worse outcome, 72% at 1 yr versus those with one or more antigen matching at each loci with a 1-yr graft survival of 81% and 2-yr graft survival of 69%. The long-term improved outcome from better antigen matching suggests that cadaver donor allograft organ assignment should address both the need of the center-driven and patient-driven concepts of recipient selection to achieve the best use of this scarce resource and an improved quality of life. PMID- 1498281 TI - Hyperlipidemia and transplantation: etiologic factors and therapy. AB - Hyperlipidemia is a well-recognized complication of renal transplantation. In long-term survivors of renal transplantation, cardiovascular disease accounts for the majority of patient deaths. In the cyclosporine era, cardiovascular disease has surpassed infection as the number one cause of death. Risk factors in the transplant population for hyperlipidemia include age, male sex, diabetes, prednisone dose, graft impairment, obesity, and antihypertensive therapy. Recently, cyclosporine has been implicated as an aggravating factor in the development of hyperlipidemia after transplantation, although its role has been controversial. Because renal transplant recipients have other significant risk factors for the development of coronary artery disease, the amelioration of hyperlipidemia may improve long-term patient survival. Because most late deaths occur in patients with a functioning graft, long-term graft survival could also be improved. The role of corticosteroids in the development of hyperlipidemia is well established. Recent studies employing corticosteroid withdrawal after transplantation have shown a marked reduction in cholesterol despite the use of cyclosporine. Data on corticosteroid withdrawal in living related transplants at our center show a significant reduction in total cholesterol after steroid withdrawal. Data from heart transplant recipients under corticosteroid-free protocols show a similar reduction in total cholesterol. Other treatments for hyperlipidemia include diet and cholesterol-lowering agents, such as Mevacor (lovastatin; Merck Sharp & Dohme, West Point, PA). The efficacy of lowering cholesterol in this high-risk population is unknown. PMID- 1498282 TI - Cyclosporine and posttransplant hypertension. AB - Prevalence studies suggest that hypertension is present in more than 50% of kidney transplant patients. It is more prevalent in pediatric patients, and cyclosporine has added to the rates in both children and adults. Hypertension is an important risk factor for cardiovascular disease, which remains the leading cause of death for recipients of renal transplants. Fortunately, posttransplant hypertension is commonly mild to moderate in nature (transplant artery stenosis hypertension being the exception) and can be treated medically. However, the removal of native kidneys and the correction of arterial stenosis are two surgical interventions that are more common in the transplant population than in the general population. In posttransplant hypertension that is primarily due to cyclosporine, one must balance the risks of reduced cyclosporine dosage against the risks of the hypertension. Both diuretic and calcium channel blocker therapy are believed to be useful in cyclosporine-induced hypertension. Other vasodilators also may be effective, although they may have undesired effects on RBF and glomerular filtration. PMID- 1498283 TI - Long-term results of cyclosporin A therapy in children. AB - In order to assess the long-term effectiveness and tolerability of cyclosporin A (CsA) treatment in children with renal transplantation (Tx), the follow-ups of 32 children (17 boys, 15 girls; age at Tx = 12.2 yr; range, 5.1 to 16.9) with a functioning graft of greater than or equal to 5 yr and continuous treatment with CsA and low-dose prednisolone are analyzed retrospectively. For comparison, data of 34 children (19 boys, 15 girls; age at Tx, 11.0; range, 3.2 to 17.1) are collected who had received a graft before the introduction of CsA, had at least 5 yr of graft function, and were continuously treated with azathioprine (AZA) plus high-dose prednisolone. The mean observation period in the CsA group was 6.5 (range, 5.0 to 8.0) yr, and in the AZA group was 10.4 yr (range, 5.7 to 15.8). CsA dosage remained unchanged in the range of 200 mg/m2/day; CsA whole blood trough level was 120 to 130 ng/mL throughout the years. One patient died in each group. Four more grafts were lost in the CsA group by chronic rejection, which was associated with noncompliance in three, and two grafts were lost in the AZA group by chronic rejection. Late acute reversible rejection episodes occurred more frequent in the CsA (six) than in the AZA group (two). The overall survival rates for patients and grafts were significantly better with CsA. The graft function in CsA-treated recipients was significantly lower than that in AZA patients, but there was no progressive loss over the years.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1498284 TI - Recurrence of primary renal disease on kidney graft: a European pediatric experience. AB - Of the 4,776 first grafts recorded in the pediatric European Dialysis and Transplant Association (EDTA) registry, 2,113 were reported to have failed and 5.6% of graft failures were related to a recurrence of primary renal disease. Nephrotic syndrome with focal and segmental glomerulosclerosis was the main renal disease prone to recur because recurrence represented 20% of the causes of graft failure in these patients; an even higher proportion was reported in a single center experience in Europe. Other glomerulonephropathies, such as membranoproliferative glomerulonephritis and Berger's disease, were also reported to be the cause of graft failure by means of recurrence in a proportion similar to focal and segmental glomerulosclerosis. The usual recurrence of primary oxaluria was the cause of close to 50% of graft failure in this disease. Finally, hemolytic uremic syndrome recurred rarely with the graft in the EDTA registry, which is the opposite of what was reported in the United States. PMID- 1498285 TI - Recurrence of focal segmental glomerulosclerosis posttransplantation: a special report of the North American Pediatric Renal Transplant Cooperative Study. AB - Among various forms of glomerulonephritis, focal segmental glomerulosclerosis (FSGS) is the most common cause of end-stage renal disease leading to transplantation in children. Previous reports of the recurrence of FSGS vary widely. The North American Pediatric Renal Transplant Cooperative Study carried out a special study to determine the rate of recurrence and risk factors leading to recurrence in 132 transplants. Fifty-five percent of the patients were white children, and the remaining were black and Hispanic children. Fifty percent of the patients were under 5 yr of age at the time of the diagnosis of FSGS. Twenty seven (20.5%) of 132 patients (95% confidence interval, 14 to 27) had a biopsy proven recurrence of FSGS. The median time to recurrence was 14 days. The recurrence rate was similar in white children (23%) when compared with that in Hispanic children (20%) but was lower than that in black children (9%) (3 of 32 children).2+ (20%). The mean serum albumin level of patients with recurrence was 1.7 versus 2.0 g/dL for those without recurrence. The mean serum cholesterol level of patients with recurrence was 525 versus 476 mg/dL for those without recurrence. The duration of dialysis was similar in the two groups. The mean time from diagnosis to end-stage renal disease status was 33 months for patients with recurrence and 52 months for those without recurrence (P less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1498286 TI - Opportunistic fungal and bacterial infection in the renal transplant recipient. AB - The risk of opportunistic infection in the renal transplant recipient is determined by the interaction between two factors: the epidemiologic exposures the individual encounters within the community and the hospital and a complex function termed the net state of immunosuppression. There are two general categories of opportunistic fungal infection in this patient population: (1) disseminated primary or reactivation infection with one of the geographically restricted systemic mycoses (histoplasmosis, coccidioidomycosis, blastomycosis, and paracoccidioidomycosis) and (2) opportunistic infection with fungal species that rarely cause invasive infection in the normal host (Aspergillus species, Candida species, Cryptococcus neoformans, and the Mucoraceae), with these last usually being acquired within the hospital environment. Newly available azole compounds, fluconazole and itraconazole, are exciting new alternatives to amphotericin in the treatment of at least some of these infections. The three most important forms of opportunistic bacterial infections are those due to Listeria monocytogenes, Nocardia asteroides, and a variety of mycobacterial species. Clinical diseases with these first two are effectively prevented by low dose trimethoprim-sulfamethoxazole prophylaxis. There are two cardinal therapeutic rules to be followed by clinicians in dealing with these infections: prevention is better than treatment; when treatment is required, however, the major determinant of the success of therapy is the rapidity with which the diagnosis is made and effective therapy is initiated. PMID- 1498287 TI - Extended recombinant human growth hormone treatment after renal transplantation in children. AB - Recombinant human growth hormone (rhGH) was administered to 13 pediatric renal allograft recipients, ages 7.6 to 17.7 yr, who were 14 to 92 months posttransplant and growth retarded as manifested by either a standard deviation (SD) more negative than -2.00 or a height velocity index of less than 25%. The rhGH was given either daily or thrice weekly (0.375 mg/kg/wk) for a period of 12 to 36 months. Growth velocity increased from 2.7 +/- 2.1 SD for the 12-month period before the initiation of treatment of 6.3 +/- 2.9 SD (P less than 0.00005) and 5.2 +/- 2.9 SD (P less than 0.02) after 12 and 24 months of treatment, respectively. Although individual recipients had improvement in their SD scores, the mean values did not increase despite the increased growth velocity. Except for a 0.5-yr increase over 24 months in two recipients, the bone age did not increase at a rate greater than the increase in chronologic age. Four rejection episodes occurred in two recipients during rhGH treatment--an incidence not greater than that which occurred during a comparable time interval before the initiation of treatment. The calculated creatinine clearance declined from 66 +/- 26 SD mL/min/1.73 m2 at the initiation of treatment to 55 +/- 30 SD mL/min/1.73 m2 at 24 months and 52 +/- 28 SD mL/min/1.73 m2 (P = not significant).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1498288 TI - Growth hormone in renal transplantation--the mode of action, animal studies, and clinical use. AB - During circulation, growth hormone (GH) is bound to about 50% by the high affinity, low-capacity GH-binding protein (BP). GHBP represents the extracellular binding domain of the GH receptor and modulates the action of GH. After binding to its receptor, GH induces the local production of insulin-like growth factor 1 (IGF-1) by autocrine and paracrine mechanisms. In uremia, the plasma GH-binding activity is low and does not get up-regulated by recombinant human GH treatment, which is in contrast to the experience in short, normal children. There is evidence that hepatic IGF-1 production is low, whereas the serum concentration of IGF-binding protein 3 (IGF-BP3) and other IGFBPs is increased because of the reduced renal clearance of the low-molecular-weight fragment of IGF-BP. This result in the reduced bioavailability of free IGF-1 and reduced IGF bioactivity. There is a strong interaction between GH and corticosteroids. Corticosteroids suppress growth by reducing the food efficiency ratio (weight gain per food intake), reduce pituitary GH secretion, and decrease the local production of and cell responsiveness for IGF-1. The growth-depressing and catabolic effects of corticosteroids can be counterbalanced dose dependently by recombinant human GH in animal experiments, and growth can be improved in corticosteroid-treated renal allograft recipients with and without normal renal function. It is not clear at this time to what extent GH may induce acute or chronic rejection crises. PMID- 1498289 TI - Factors affecting growth after renal transplantation. AB - Renal transplantation has been recognized as the treatment of choice for children with chronic renal failure principally because it can normalize their physiologic status and thus provide them with the potential for normal growth. The results of renal transplantation, however, have been mixed with some reports of excellent posttransplant growth and others with less optimistic results. Some of the differences among these studies may be because of the use of multiple methods to assess the success or failure of posttransplant growth. The usual methods have included assessment of the final adult height, growth velocity, presence of accelerated growth rates, change in height standard deviation scores, and growth survival. All of these methods have advantages and disadvantages in the description of the success or failure of growth after renal transplantation, but no single method stands out as the most appropriate to use in all circumstances. Furthermore, growth is dependent on a large number of complex and interrelated factors. At least four of these factors have been shown to affect the growth rates of children after renal transplantation: age at the time of transplant; allograft function; the type, dose, and schedule of immunosuppressive medication; and other endocrinologic factors. Finally, analysis of long-term growth patterns in children after renal transplantation has shown that growth rates frequently decrease over time. Even children who have grown well immediately after the transplant may develop growth failure after several years. We conclude that the majority of children with renal transplants can experience normal or even accelerated growth rates after the procedure. Unfortunately, growth rates subsequently tend to decline in most children.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1498290 TI - Sequential therapy in pediatric cadaveric renal transplantation: a critical analysis. AB - Cadaveric renal transplant survival rates in children are still somewhat inferior to those reported in adults. Sequential therapy, an immunosuppressive program in which a course of antilymphocyte preparation is used immediately postoperatively and followed in sequence by oral maintenance immunosuppression, has a number of features that might be expected to improve pediatric transplant outcome by addressing some of the metabolic and immunologic difficulties encountered in children. This article examines the rationale for sequential therapy in pediatric renal transplantation. It also examines the use of sequential therapy in children. Sequential therapy appears to significantly improve cadaver renal allograft outcome in children without compromising patient survival. There was a slight improvement in 1- and 2-yr graft outcomes when OKT3 was used prophylactically when compared with antithymocyte globulin, but this difference did not reach statistical significance. Almost 60% of patients receiving OKT3 for sequential therapy remained free of rejection. Major drawbacks of sequential therapy include the adverse side effects of the antilymphocyte preparation, infection, and the possibility of lymphoproliferative syndrome. The implications of these problems as well as potential strategies for ameliorating them are discussed. PMID- 1498291 TI - Subspecialty training in anesthesia: cardiac anesthesia faces a dilemma. PMID- 1498292 TI - The effect of the extended (3-year) anesthesia curriculum on anesthesia subspecialty education. AB - The purpose of this study was to determine the effect of lengthening the anesthesia residency by the American Board of Anesthesiology on the education of anesthesia subspecialists. A survey of anesthesia residency programs was conducted from 1987 to 1991. The most frequent subspecialty practice in the clinical anesthesia (CA) 3 year is cardiovascular anesthesia. However, the percentage of CA3 residents spending extended time (greater than or equal to 6 months) in subspecialty education has significantly decreased. For example, the percentage of CA3 residents spending 12 months in subspecialty education has decreased 83%. There appears to be a slight increase in the number of CA4 or PGY5 residents (fellows) electing subspecialty practice. It is concluded that the 3 year curriculum has produced a negative impact on the education of anesthesia subspecialists. PMID- 1498293 TI - Resident clinical competence in cardiac anesthesia: a case performance-based evaluation study. AB - The purpose of this study was to estimate the minimum number of cases that anesthesiology residents need to complete in order to master the clinical skills required in cardiac anesthesia. In addition, the extent to which the resident's general anesthesia experience and in-training examination scores influence clinical performance was also studied. The data presented were based on observation of 99 actual cases, which were managed by 16 residents. A performance based evaluation approach was developed, encompassing nine clinical performance skills considered essential to effective and safe cardiac anesthesia management. It was determined that there was consistent improvement in every clinical skill with the number of cardiac cases managed, except for preanesthetic assessment. The minimum number of cardiac cases that residents needed to manage before achieving a satisfactory level of skill ranged from about 10 cases for preoperative assessment to 20 to 30 cases for hemodynamic and coagulation management. It is concluded that residents needed different lengths of time to develop different skills, and it is logical to look at each basic skill independently in the evaluation of resident progress. Based on the findings of this study, it is suggested that a case performance-based evaluation approach might provide a more objective and accurate means for assessing resident progress in cardiac anesthesia. PMID- 1498294 TI - The relationship among bronchial blocker cuff inflation volume, proximal airway pressure, and seal of the bronchial blocker cuff. AB - The resting volume and diameter of the bronchial blocker cuff (defined as inflation of the cuff to just its natural shape) of the Univent (Fuji Systems Corp, Tokyo, Japan) tube are 2 mL and 5 mm. However, much larger inflation volumes may be required to seal an adult mainstem bronchus and the surface area of contact between the resultant spherical or ellipsoid-shaped cuff and the wall of the mainstem bronchus may be small and susceptible to leak with the application of high proximal airway pressures. This experiment determined the relationship among airway diameter, proximal airway pressure, inflation volume of the bronchial blocker cuff, and leakage of air around the bronchial blocker cuff in an in vitro model. The experimental model consisted of silicon tubing of 12.8 , 16.0-, and 19.2-mm ID as the mainstem bronchus. The main tracheal cuff sealed the Univent tube into the proximal end of the mainstem bronchus and the bronchial blocker cuff was inflated with various volumes near the distal end of the mainstem bronchus. The space between the tracheal cuff and the bronchial blocker cuff was then progressively pressurized in either a static or pulsed manner. The very distal end of the bronchus was functionally submerged under a beaker of water so that a bronchial blocker cuff leak would be indicated by bubbling. It was found that the Univent bronchial blocker cuff sealed the 12.8- and 16.0-mm ID mainstem bronchi against airway pressures as great as 100 cmH2O, with inflation volumes that were within the manufacturer's recommendation of 6 to 7 mL.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1498295 TI - Anesthesia for bilateral lung transplantation without cardiopulmonary bypass: initial experience and review of intraoperative problems. AB - Bilateral lung transplantation (BLT) is a recently described procedure based on two sequential single-lung transplantations (SLT), which are performed by a transverse sternobithoracotomy. It does not require either cardiac arrest or routine use of cardiopulmonary bypass (CPB). The intraoperative management of 10 patients suffering from end-stage pulmonary disease is reported. Implantation of the first graft is quite similar to a SLT. Problems encountered during this procedure (ie, hypoxemia, hypercapnia, or low cardiac output) were due to restricted pulmonary and cardiac reserve. Preoperative and intraoperative assessment of the recipient's respiratory and cardiac status was, therefore, of prime importance. Mild preoperative pulmonary hypertension, well-preserved right ventricular function, and removal of the less well-perfused lung limited these difficulties; no patient required partial CPB at this stage. During the second lung implantation, gas exchange was provided by the first grafted lung. Measurements of pulmonary vascular resistance (PVR), venous admixture (Qva/Qt), and dead space (VD/VT) assessed with the arterial-to-end-tidal CO2 difference were used to confirm the adequacy of perfusion and V/Q matching. In one patient, partial CPB was instituted because of surgical difficulty related to inadequate size matching of the lungs. In the other patients, first graft function was satisfactory and the second graft was implanted without CPB. With chest closure, PVR returned to nearly normal values (range, 57-293, mean 167 dynes.s.cm-5) and Qva/Qt increased (range, 3 to 36, mean 20%). This limited series demonstrates that CPB is optional during this procedure. Good selection of recipients and donors, good lung preservation methods, and a short duration of cold ischemia are essential to success. PMID- 1498296 TI - Hemodynamic effect of calcium channel blockade during anesthesia for coronary artery surgery. AB - Because the choice of anesthetic technique does not influence the incidence of perioperative myocardial ischemia, reduction of ischemic risk may require specific antianginal therapy. Calcium entry blockers are effective drugs in antianginal therapy. Diltiazem reduces myocardial oxygen demand through decreases in heart rate, inotropy, and systolic function, while increasing myocardial oxygen delivery through coronary vasodilation. These potentially beneficial effects of diltiazem were evaluated in 15 of 29 patients (diltiazem v placebo, double-blind study) scheduled for coronary artery bypass graft surgery. Continuous infusion of diltiazem (0.15 mg/kg bolus followed by 2 micrograms/kg/min), during anesthesia and surgery before cardiopulmonary bypass, significantly reduced the major MVO2 determinants during anesthesia with moderate doses of fentanyl and a benzodiazepine (midazolam in 8 of 14 control patients and 9 of 15 treated patients, or flunitrazepam in the others). Heart rate, mean arterial pressure, and inotropy were decreased during the most stressful events of surgery when plasma diltiazem concentrations were in the therapeutic range (greater than 96 ng/mL). The number of patients with perioperative ischemia was 2 of 15 in the treated group and 4 of 14 in the control group. Provided that diltiazem plasma concentrations are sufficient, it can contribute to lowering the ischemic burden during anesthesia for coronary artery surgery. PMID- 1498297 TI - Prognostic value of biventricular function in hypotensive patients after cardiac surgery as assessed by transesophageal echocardiography. AB - In patients after cardiac surgery, hypotension, defined as a mean arterial pressure less than 65 mmHg despite adequate filling pressures and positive inotropic medication, poses a problem. In addition, it is often difficult to determine whether these patients have suffered irreversible myocardial injury or if they are likely to recover. In this study, left and right ventricular function, as assessed by transesophageal echocardiography (TEE), was related to mortality both (1) quantitatively, using fractional area change (FAC), and (2) qualitatively, using a segmental wall motion analysis, which assigned a score to myocardial wall segments, in order to determine whether this technique can be used to predict survival. Mortality rate was very high in patients with biventricular and especially right ventricular failure (FAC less than 35%). Left and right ventricular wall motion abnormality indices were significantly better in survivors compared to nonsurvivors, but no distinct cut-off value could be determined. A wall motion index derived from only 6 segments at the mid-papillary muscle level was found to be as reliable as one based on 16 segments of the entire left ventricle. Thus, TEE provided information about the degree of left and right ventricular dysfunction by using a single cross-section at the papillary muscle level. It identified patients at high risk of death, ie, those with compromised right and biventricular function. PMID- 1498299 TI - Transesophageal Echo-doppler evaluation of the hemodynamic effects of positive pressure ventilation after coronary artery surgery. AB - Transesophageal echocardiography was used to extend knowledge about the impact of positive end-expiratory pressure (PEEP) during mechanical ventilation on right and left ventricular function and right ventricular impedance. At 20 cmH2O PEEP, a progressive increase of right ventricular end-diastolic area was seen (27%) that coincided with a reduction of early left ventricular filling velocity (25%) across the mitral valve, and a decrease of both pulmonary artery flow velocity (end-expiration 27% and end-inspiration 42%) and time-velocity index (end inspiration 25%). As these changes were not accompanied by a change of the fractional area of contraction, the increase of the right ventricular diameter might be explained by right ventricular compensation due to an imbalance between augmented right ventricular impedance and reduced venous return. PMID- 1498298 TI - Transesophageal echocardiographic assessment of left ventricular function in response to labetalol for control of postoperative hypertension. AB - Although labetalol (LAB), the combination of an alpha- and beta-adrenergic blocking agent, is thought to be effective and safe for the control of postoperative hypertension, no study has focused on changes in left ventricular (LV) function when this drug was used to control postoperative hypertension. Therefore, this study determined the effects of LAB on hemodynamics and LV function assessed by 2D transesophageal echocardiography (TEE) in 17 patients undergoing abdominal aortic surgery who experienced a postoperative hypertensive episode. Postoperatively, patients were transferred while still intubated and under fentanyl sedation to the postanesthesia care unit where a TEE probe was inserted to provide a short-axis view of the LV. When their systolic blood pressure increased above 165 mmHg for more than 4 minutes, LAB was given in a dose of 0.75 mg/kg IV, over 2 minutes. If the blood pressure was not lowered to within 10% of the preoperative values, additional doses of LAB were given. Control of hypertension was obtained in all patients and was associated with a significant decrease in heart rate (90 +/- 19 to 70 + 13 bpm), cardiac index (4.52 +/- 1.65 to 3.36 +/- 1.55 L/min/m2), and mixed venous oxygen saturation (73 +/- 10 to 63 +/- 10%). With the lower blood pressure, end-diastolic area increased, indicating myocardial depression. In conclusion, LAB can be used to effectively control hypertension during the early postoperative period after abdominal aortic surgery. However, the reduction of blood pressure is achieved principally by the negative inotropic effect of LAB, which predominates over its vasodilator action. PMID- 1498300 TI - Effects of fentanyl-diazepam-pancuronium anesthesia on heart rate variability: a spectral analysis. AB - The effects of induction of anesthesia with fentanyl, 62.1 +/- 7.9 micrograms/kg, diazepam, 0.21 +/- 0.08 mg/kg, and pancuronium on beat-to-beat heart rate variations were studied in seven patients undergoing cardiac surgery. Spectral analysis was used to determine the intensity of the variations in each of the two main frequency bands in which variations are known to occur: (1) high-frequency band, mediated by the parasympathetic nervous system, at the frequency band of respiration, and (2) the low-frequency band, mediated by both sympathetic and parasympathetic nervous systems, at 0.04-0.12 Hz. Both the mean low- and high frequency band areas were significantly decreased after induction of anesthesia. The ratio of high-to-low frequency band areas increased significantly after induction of anesthesia, from 45% to 62% (P less than 0.05). These results suggest that fentanyl-diazepam-pancuronium anesthesia decreases total autonomic nervous system activity and alters the balance between parasympathetic and sympathetic activities. Thus, spectral analysis of heart rate variations during anesthesia may provide a quantitative measure of assessing the activity of the autonomic nervous system. PMID- 1498301 TI - The appearance of large "V" waves in association with sternal retraction during coronary artery surgery. PMID- 1498302 TI - Ketorolac tromethamine may be efficacious in treating hypotension from mesenteric traction. PMID- 1498303 TI - The use of a somatostatin analog in the treatment of refractory hypotension after cardiopulmonary bypass. PMID- 1498304 TI - Anesthetic considerations in a cardiac surgical patient with Osler-Weber-Rendu disease. PMID- 1498305 TI - The modified Fontan procedure: physiology and anesthetic implications. AB - The modified Fontan operation has gained wide acceptance as a functional corrective procedure for patients with CHD with single ventricle physiology. Long term survival and palliation of symptoms are excellent with most patients able to lead normal lives. The absence of a pulmonary contractile ventricle means that the single ventricle is responsible for perfusion of both the pulmonary and systemic circulations. Elevated systemic venous pressure is required to overcome PVR and this state of systemic venous hypertension has a significant impact on the anesthetic and postoperative care of these patients. PMID- 1498306 TI - Case 4--1992. A 62-year-old man is scheduled for a new cardiac surgical procedure: dynamic cardiomyoplasty. PMID- 1498307 TI - Pro: early endotracheal extubation is preferable to late extubation in patients following coronary artery surgery. AB - Prolonged mechanical ventilation following CABG should not be uncritically considered "routine," and should only be used where indicated. A thorough physiologic and clinical evaluation with attention to hemodynamics, neurologic status, temperature and metabolism, hemostasis, and respiratory reserve should precede extubation. Continued post-operative ventilation is indicated in patients at high risk for complications, and it is possible to identify this subset preoperatively and upon arrival in the postoperative ICU. Early extubation (within 8 hours of arrival) should otherwise be the goal. The benefits of early extubation include improved cardiac function and patient comfort, reduction in respiratory complications, ease in management, and cost savings as the result of shortened length-of-stay in expensive postoperative units. More research is needed to clarify unanswered questions regarding ablating the stress response and avoiding myocardial ischemia. PMID- 1498308 TI - Con: early extubation is not preferable to late extubation in patients undergoing coronary artery surgery. PMID- 1498309 TI - Cardiopulmonary resuscitation: state of the art. PMID- 1498310 TI - A bleeding swan. PMID- 1498311 TI - Sickle cell trait, open heart surgery, and SVO2. PMID- 1498312 TI - Radiographic pulmonary abnormalities after pediatric cardiac surgery. PMID- 1498313 TI - Acute hemolysis in glutathione peroxidase deficiency. AB - Severe acute hemoglobinemia and hemoglobinuria developed in a 17-year-old Japanese male with no history of exposure to any oxidizing agents. Examination of erythrocyte enzyme activity revealed that the patient's erythrocyte glutathione peroxidase (GSH-Px) activity was decreased to about a half that in control cells. Serum selenium (Se) concentration was within normal limits. Family studies showed that GSH-Px activity in the erythrocytes of two siblings was similarly decreased. It was suggested that the proband was suffering from a hereditary heterozygous GSH-Px deficiency, which appeared to be associated with acute hemolysis. PMID- 1498314 TI - High serum human macrophage colony-stimulating factor level during pregnancy. AB - Using a specific enzyme immunoassay, we monitored the serum levels of human macrophage colony-stimulating factor (hM-CSF) in pregnant women during gestation and after delivery. During pregnancy there was a marked elevation of maternal serum hM-CSF level, which returned to the baseline level within 3 weeks after delivery. The changes in maternal serum hM-CSF level were associated with changes in the numbers of monocytes and neutrophils in the maternal peripheral blood. Fetal sera prepared from cord blood samples also had a high hM-CSF level. In contrast to the baseline level of hM-CSF in maternal sera after delivery, the hM CSF levels of newborn infants at 1 to 7 days after birth were higher than fetal levels, indicating that fetuses and newborn infants are a source of hM-CSF. The serum hM-CSF levels of infants at 22 to 35 days were between fetal levels and normal adult levels. Human M-CSF found in the serum of pregnant women and in cord blood was predominantly the large form of M-CSF, with a molecular mass of 85 kDa. Human M-CSF levels in amniotic fluid at 30 to 40 weeks were higher than those in cord blood sera at the same stage, indicating that the uterus is another source of hM-CSF. The roles played by hM-CSF during pregnancy need to be investigated. PMID- 1498315 TI - Bone marrow transplantation for chronic myelogenous leukemia in blastic phase using a phenotypically identical unrelated volunteer donor. Nagoya Bone Marrow Transplantation Group (NBMTG), Tokai Marrow Donor Bank (TMDB). AB - A 26-year-old male with chronic myelogenous leukemia in lymphoid blast crisis received a bone marrow transplant (BMT) from a phenotypically identical, mixed lymphocyte reaction (MLR)-weakly positive unrelated male volunteer donor. The volunteer was obtained from the Tokai Marrow Donor Bank (TMDB), which was established in Japan in 1989. This donor was selected from volunteer donors who were identical with our patient at the HLA-A,B loci, followed by matching at HLA DQ, DR loci. On MLR testing, the donor's cells showed no response, but the patient's cells showed a low response to the donor's cells (relative response index 0.29). The patient showed rapid hemopoietic engraftment. He developed acute graft-versus-host disease (GVHD) with vesicle formation on palms and soles and mild liver damage, which were successfully treated with intravenous prednisolone 1 mg/kg per day. Although he also suffered from interstitial pneumonitis on day 64 and localized varicella-zoster infection on day 87, and has suffered from moderate stomatitis and dry skin characteristic of chronic GVHD, he is currently 22 months post-transplant with hematological remission and has a normal daily social life. PMID- 1498316 TI - GM-CSF-mediated proliferation induction improves the susceptibility of leukemia cells to lymphokine-activated killer cells. AB - Our studies on the susceptibility of fresh noncultured leukemia cells to interleukin-2 (IL-2)-induced lymphokine-activated killer (LAK) cells have shown that about two thirds of the leukemias are susceptible to the LAK-cell-mediated cytolysis. Analysis of 214 acute leukemias revealed considerable variation in the degree of cytotoxicity achieved. Cytolysis was substantially lower in fresh noncultured acute leukemia samples than in K562 and Daudi cell lines (mean Cr release 21.0 +/- 16.0% versus 69.2 +/- 6.6% and 70.8 +/- 7.9%). Augmentation of susceptibility to LAK-cell lysis is desirable in connection with therapeutic application of IL-2-induced effector mechanisms. We observed a relationship between the LAK-cell susceptibility of leukemia cells and their spontaneous proliferation rate, which is significantly higher in LAK-cell-sensitive than in LAK-cell-resistant leukemias. It was therefore considered useful to examine the possibility of augmenting LAK-cell sensitivity by proliferation induction. These studies demonstrate that incubation of blast cells from acute myeloid leukemia (AML) and chronic myelogenous leukemia in myeloid blast crisis (CML-BC) with recombinant granulocyte-macrophage colony stimulating factor (GM-CSF) significantly augments LAK-cell susceptibility and that this is associated with an increased cell proliferation. PMID- 1498317 TI - Colloidal gold uptake as a marker for monocyte differentiation and maturation in normal and leukemic cells. AB - The uptake of colloidal gold particles by human monocytes was studied by electron microscopy, with special emphasis on changes in this uptake during the differentiation and maturation of these cells. The way in which leukemic cells of childhood acute non-lymphocytic leukemia (ANLL) can function in this gold uptake was also examined. In monocytes, microendocytosis was temperature-dependent; colloidal gold uptake increased as temperatures rose from 4 degrees C to 37 degrees C. It appeared that gold particles first adhered to the cell surface membrane, were then incorporated into the cytoplasmic vesicles, and then were transported into the granules. Original HL-60 cells and retinoic acid (RA) treated HL-60 cells, which were differentiating and maturing along the granulocyte lineage, did not ingest colloidal gold particles, but 1,25(OH)2D3 treated HL-60 cells showed colloidal gold uptake during their differentiation and maturation along the monocyte lineage: 68.6% of the cells contained gold particles. Gold uptake was demonstrated in 27.3% of original U937 cells; the percentage increased to 70.3% when they were induced to mature by RA. In 15 specimens of childhood ANLL, none of the M1, M2 or M3 cells showed colloidal gold uptake, whereas 76-97% of M4 and M5 cells showed this uptake. These findings indicate that colloidal gold uptake is a marker of monocyte differentiation and maturation and can provide additional information for ANLL cytology. PMID- 1498318 TI - Perivascular Ki-1 + lesions. AB - We describe three male patients diagnosed by histologic and immunophenotypic criteria to have a Ki-1 + lymphoproliferative disorder. All three cases shared a unique morphologic finding, not previously described: prominent perivascular cuffing of anaplastic/pleomorphic tumor cells around small and medium sized vessels. One case was a Ki-1 + anaplastic large cell lymphoma (ALCL) which developed in the setting of a low grade follicular B-cell lymphoma. A pseudoglandular pattern caused referral for consultation as a possible adenocarcinoma. One case was a cutaneous Ki-1 + lymphoproliferative disorder consistent with lymphomatoid papulosis (LyP). The third case was a cutaneous Ki-1 + ALCL. This study provides evidence that although perivascular cuffing of tumor cells is not frequently seen in Ki-1 + lymphoproliferative disorders (3 of 116 cases in our consultation file), it may be a prominent architectural feature causing confusion with epithelial or mesenchymal tumors. For this reason we recommend inclusion of this feature in the list of architectural features already described for Ki-1 + lymphoproliferative disorders. PMID- 1498319 TI - A multicenter prospective study on the treatment of chronic idiopathic thrombocytopenic purpura. AB - A multicenter prospective study on the treatment of chronic idiopathic thrombocytopenic purpura (ITP) was conducted by the Idiopathic Disorders of Hematopoietic Organs Research Committee (IDHORC), the Ministry of Health and Welfare of Japan. The aim of the study was to establish an improved therapeutic guide for chronic ITP. Of the 247 eligible patients 175 have been followed up to the present time, 16 patients have died, and 56 have been lost to follow-up. The median follow-up time was 55 months (range: 1 to 91 months). Of the 206 patients treated with corticosteroids, 13.1% achieved sustained complete remission. Splenectomy produced remissions in 52.5% of 72 patients evaluated 12 months after operation. Eighty-five patients were treated with immunosuppressive agents, but the response rates were low and the effect was transient in most cases. In the patients followed up without any specific treatment, the mean platelet counts showed slight improvement. Of the 16 patients who died during the observation period, only one died of bleeding; the remaining 15 died of causes unrelated to thrombocytopenia. It is noteworthy that five patients who were treated with corticosteroids or immunosuppressive agents died of infection. PMID- 1498320 TI - Danazol therapy in idiopathic thrombocytopenic purpura: the efficacy of low medium dose therapy. AB - To examine the effects and optimal dose of danazol on idiopathic thrombocytopenic purpura (ITP), we administered a low-medium dose to 14 patients with this disease. A low-medium dose of danazol was effective in maintaining the platelet count at a high level, even after the dose of prednisolone was reduced. A low medium dose of danazol without other therapy was effective in 3 of 6 patients even after they had been refractory to other treatment. A low dose of danazol was also effective in some patients for whom the other regimes were not indicated. It is concluded that a low-medium dose of danazol instead of a high dose is worth trying in ITP when the patient has become refractory to other therapeutic approaches or when these are not indicated. PMID- 1498321 TI - Frequent clonal proliferation of human T-cell leukemia virus type 1 (HTLV-1) infected T cells in HTLV-1-associated myelopathy (HAM-TSP). AB - Human T-cell leukemia virus type 1 (HTLV-1) integrates its proviruses into random sites in host chromosomal DNA. Random integration of the proviruses was observed in asymptomatic HTLV-1 carriers and patients with HTLV-1-associated myelopathy (HAM/TSP). However, clonal integration has been reported in patients with adult T cell leukemia (ATL), including that in the smoldering, chronic, and acute states, indicating clonal expansion of infected cells. In this study, we found that about 20% of HAM/TSP patients and their seropositive family members harbored subpopulation(s) of clonally proliferated cells infected with HTLV-1, although they still maintained randomly infected cells as a major population. These clones were stable during examination periods of 4 months to 3 years. However, these carriers or HAM/TSP patients did not show any significant indication of ATL. This extremely high frequency of clonal expansion of HTLV-1-infected cells indicates that some clones of HTLV-1-infected cells have a tendency to proliferate more efficiently than the other population without malignant transformation. PMID- 1498322 TI - Simultaneous genotypic and immunophenotypic analysis of interphase cells using dual-color fluorescence: a demonstration of lineage involvement in polycythemia vera. AB - Fluorescent in situ hybridization has become a useful technique by which chromosomal abnormalities may be shown in interphase cells. We present a dual fluorescence method whereby a chromosomal and immunophenotypic marker can be visualized simultaneously in the same interphase cell. Two patients with the myeloproliferative disorder polycythemia vera and trisomy for chromosome 8 have been studied using this technique and selective involvement of the myeloid and erythrocyte lineages has been shown by the detection of the trisomy in immunophenotyped cells. Simultaneous analysis of genotype and immunophenotype in individual cells from patients with myeloproliferative disorders or leukemia may help identify the developmental and lineage status of cells in which molecular alterations have resulted in clonal advantage. PMID- 1498323 TI - Blood platelets stimulate the expression of chondroitin sulfate proteoglycan in human monocytes. AB - Mononuclear phagocytes synthesize chondroitin sulfate proteoglycan (CSPG), which is constitutively secreted. Because mononuclear phagocytes are known to interact with blood platelets, the effect of platelets on the release of CSPG in cultured human monocytes was investigated. After 6 days in vitro, the monocytes were supplied with fresh medium with different additions and subsequently exposed to [35S]sulfate for 24 hours before the medium fractions were harvested and analyzed for content of [35S]CSPG. Indirect evidence for the release of stimulatory factors from blood platelets was found when the addition of medium containing 50% serum made from platelet-rich plasma increased the expression of [35S]CSPG almost sevenfold compared with serum-free medium, whereas medium containing 50% serum made from platelet-depleted plasma increased the expression of [35S]CSPG about fourfold. Further, direct evidence for the stimulatory effect of platelets was found as the addition of autologous platelets to serum-free medium increased the expression of [35S]CSPG about threefold, and addition of supernatant from a corresponding number of thrombin-stimulated platelets was almost as efficient. The effect of five different platelet-derived factors (which are all present in serum) was investigated. Both platelet-derived growth factor (PDGF), platelet factor 4 (PF 4), and prostaglandin E2 (PGE2) used in physiologic concentrations were found to stimulate the expression of [35S]CSPG twofold to threefold, whereas transforming growth factor-beta had a slight inhibitory effect. 12 Hydroxyeicosatetraenoic acid had no significant effect on the expression of [35S]CSPG. Further evidence for the stimulatory effect of PDGF, PF 4, and PGE2 was found as serum depleted of these factors had significantly less stimulatory effect than control serum. The increased incorporation of [35S]sulfate into [35S]CSPG in cultures stimulated with serum or platelet-derived factors was not due to differences in molecular size or extent of sulfation of the proteoglycan molecules. PMID- 1498324 TI - Spectrin beta Tandil, a novel shortened beta-chain variant associated with hereditary elliptocytosis is due to a deletional frameshift mutation in the beta spectrin gene. AB - An Argentinian family with hereditary elliptocytosis (HE) associated with a shortened beta-spectrin (Sp) chain was studied. As with most of the other shortened Sp beta-chains that have been described, this variant, called SpTandil, has impaired ability to participate in Sp dimer self-association, has lost its ability to become phosphorylated, and is associated with the presence of increased amounts of the alpha I 74-Kd fragment after partial tryptic digestion of Sp. The 3' ends of the beta-Sp gene of affected patients were analyzed. cDNA was prepared by reverse transcription of peripheral blood mRNA and amplified by the polymerase chain reaction (PCR) using primers corresponding to sequences 400 bp apart on the cDNA, spanning the last three exons (X, Y, Z) of the beta-Sp gene. Agarose gel electrophoresis of the cDNA amplification showed the presence of one band, the size of which was apparently the same as the band amplified from mRNA of a normal control. cDNA from one HE patient was subcloned and sequenced. Several clones showed the presence of a 7-bp deletion at codon 2041 in exon X. Genomic DNA of all the affected members of the family were amplified by PCR using primers flanking the deletion and corresponding to sequences 128 bp apart on exon X. Analysis of the PCR products using electrophoresis on polyacrylamide gel showed the presence of 121- and 128-bp bands in all HE subjects, and an additional doublet migrating more slowly than the two bands, which corresponded to the presence of heteroduplexes. The mutation results in a shift of the normal reading frame and leads to a new amino acid sequence at the C-terminus of the mutant beta-Sp chain. A new in-frame stop codon is encountered downstream, leading to premature chain termination. The identification of the molecular defect in Sp beta Tandil provides information regarding the region of the beta-Sp chain that is important for both Sp dimer self-association and an indication of potential sites of phosphorylation of the chain. PMID- 1498325 TI - Bone marrows of non-Hodgkin's lymphoma patients with a bcl-2 translocation can be purged of polymerase chain reaction-detectable lymphoma cells using monoclonal antibodies and immunomagnetic bead depletion. AB - Using the extremely sensitive technique of polymerase chain reaction (PCR) to detect the bcl-2 translocation, only 50% of bone marrows could be purged of PCR detectable lymphoma cells using a cocktail of three anti-B-cell monoclonal antibodies (MoAbs) and complement-mediated lysis. This observation is of clinical importance because those patients whose reinfused marrows harbored residual lymphoma cells showed a significantly increased incidence of relapse. To improve purging, we used PCR detection of the bcl-2 translocation to compare the efficiency of complement-mediated lysis with immunomagnetic bead depletion. Using either a three or a four MoAb cocktail followed by immunomagnetic bead depletion, all PCR-detectable cells were purged after three cycles of treatment. In these same patient samples, treatment with three MoAbs and complement purged only 11 of the 25 (44%) samples. The addition of a fourth MoAb followed by complement lysis purged the marrows of only an additional five patients. Immunomagnetic bead depletion was specific because there was no loss of committed myeloid progenitor cells. The above results suggest that immunomagnetic bead depletion of the harvested marrow will likely be superior to our previous method of purging and the lack of nonspecific toxicity to myeloid progenitor cells predicts that it will not impair engraftment. This methodology will now be used to determine whether the reinfusion of lymphoma free marrow affects the incidence of relapse after autologous bone marrow transplantation. PMID- 1498326 TI - Bone marrow transplants may cure patients with acute leukemia never achieving remission with chemotherapy. AB - About 30% of adults with acute lymphoblastic leukemia (ALL) and 20% to 40% of children and adults with acute myelogenous leukemia (AML) never achieve remission, even with intensive chemotherapy. Most die of resistant leukemia, often within 6 months or less. In this study of 126 patients with resistant ALL or AML, allogeneic bone marrow transplants from HLA-identical siblings produced remissions in 113 of 115 (98%) evaluable patients. The 3-year probability of leukemia-free survival was 21% (95% confidence interval, 15% to 29%). Leukemia free survival was similar in ALL (23%, 12% to 40%) and AML (21%, 14% to 31%). Only 3 of 27 patients at risk relapsed more than 2 years posttransplant. PMID- 1498327 TI - Hematologists and health care policy in America. PMID- 1498328 TI - Lupus anticoagulant, anticardiolipin antibodies, fetal loss, and systemic lupus erythematosus. PMID- 1498329 TI - Monoclonal antibody-based therapies of leukemia and lymphoma. PMID- 1498330 TI - Bcl-2 initiates a new category of oncogenes: regulators of cell death. PMID- 1498331 TI - Primary dexamethasone treatment of multiple myeloma. AB - Intermittent courses of dexamethasone (DEX) were administered to 112 consecutive, previously untreated patients with multiple myeloma (MM). Using criteria based on a 75% or greater reduction of calculated tumor mass, the overall response rate was 43%. Among comparable patients, response rate were approximately 15% less than those observed previously with vincristine-doxorubicin by continuous infusion with intermittent DEX (VAD) and similar to those with melphalan prednisone. The projected survival times with VAD or DEX were similar. Results indicated that DEX accounted for most of the plasma cell reduction achieved with VAD. Serious complications occurred in 27% of patients treated with VAD, but in only 4% of those who received DEX. In view of the similar outcome with fewer serious complications, DEX provided a simple, effective, and safe primary treatment for a large fraction of patients with MM. Patients who appear most likely to benefit include those with hypercalcemia or pancytopenia, or who require simultaneous radiotherapy for a pathologic fracture. PMID- 1498332 TI - Polycythemia vera. II. Hypersensitivity of bone marrow erythroid, granulocyte macrophage, and megakaryocyte progenitor cells to interleukin-3 and granulocyte macrophage colony-stimulating factor. AB - Polycythemia vera (PV) is a clonal disease of the hematopoietic stem cell characterized by a hyperplasia of marrow erythropoiesis, granulocytopoiesis, and megakaryocytopoiesis. We previously reported that highly purified PV blood burst forming units-erythroid (BFU-E) are hypersensitive to recombinant human interleukin-3 (rIL-3). Because these cells may be only a subset, and not representative of marrow progenitors, we have now studied partially purified marrow hematopoietic progenitor cells. Dose-response experiments with PV marrow BFU-E showed a 38-fold increase in sensitivity to rIL-3 and a 4.3-fold increase in sensitivity to recombinant human erythropoietin (rEpo) compared with normal marrow BFU-E. In addition, PV marrow colony-forming units-granulocyte-macrophage (CFU-GM) and CFU-megakaryocyte (CFU-MK) also showed a marked hypersensitivity to rIL-3 and to human recombinant granulocyte-macrophage colony-stimulating factor (rGM-CSF). Dose-response curves with rGM-CSF and blood BFU-E showed a 48-fold increase in sensitivity. No effect of rIL-4, rIL-6, human recombinant granulocyte CSF (rG-CSF), or macrophage-CSF (rM-CSF) was evident, nor was there any effect of PV cell-conditioned medium on normal BFU-E, when compared with normal cell conditioned medium. Autoradiography with 125I-rEpo showed an increase in Epo receptors after maturation of PV BFU-E to CFU-E similar to that shown with normal BFU-E, but no increase of specific binding of 125I-rIL-3 by PV CD34+ cells was seen compared with normal CD34+ cells. These studies show that PV marrow hematopoietic progenitor cells are hypersensitive to rIL-3 and rGM-CSF, similar to PV blood BFU-E. While the mechanism does not appear to be due to enhanced binding of rIL-3, the hypersensitivity of PV progenitor cells to IL-3 and GM-CSF may be a key factor in the pathogenesis of PV. PMID- 1498333 TI - Binding of primitive hematopoietic progenitor cells to marrow stromal cells involves heparan sulfate. AB - Blast colony-forming cells (BI-CFC) and pre-colony-forming unit-granulocyte, monocyte (CFU-GM) in human bone marrow bind to marrow-derived stromal layers grown in the presence of methylprednisolone (MP+), but do not bind to stroma grown without MP (MP-). The BI-CFC bind to stroma and form colonies when overlaid with agar; the pre-CFU-GM bind to stroma and release CFU-GM into the supernatant culture medium (delta assay). These two classes of progenitor may represent similar stages of hematopoietic cell development. Their binding to stroma depends on the presence of heparan sulfate proteoglycan (HS-PG) in the extracellular matrix secreted by the stromal cells. Here, we have analyzed the functional and biochemical properties of HS-PG isolated from MP+ and MP- stromal cultures. HS-PG or isolated HS glycosaminoglycan (GAG) side chains partially blocked progenitor cell binding when they were added to the 2-hour binding phase of the BI-CFC or delta assays. Gel electrophoresis of HS-PG resolved more bands in matrix preparations from MP+ cultures than in preparations from MP- cultures. The blocking activity of the eluted MP+ HS-PG bands depended partly on the amount of GAG attached to the protein core and presumably partly on the structure of the core itself. Time course studies demonstrated that the HS-dependent phase of the binding interaction was limited to the first 30 to 60 minutes of the 2-hour binding phase. The different blocking effects of MP+ and MP- HS indicate that they have different biochemical properties. The HS-GAG in MP+ stroma has a higher degree of sulfation and a greater negative charge to mass ratio compared with MP- HS-GAG. Variations in HS may determine specific binding by hematopoietic progenitor cells and a heparan sulfate receptor is envisaged as acting in concert with further cell adhesion molecules (CAMs) on the progenitor cell surface. PMID- 1498334 TI - Role of individual gamma-carboxyglutamic acid residues of activated human protein C in defining its in vitro anticoagulant activity. AB - To evaluate the contributions of individual gamma-carboxyglutamic acid (gla) residues to the overall Ca(2+)-dependent anticoagulant activity of activated human protein C (APC), we used recombinant (r) DNA technology to generate protein C (PC) variants in which each of the gla precursor glutamic acid (E) residues (positions 6, 7, 14, 16, 19, 20, 25, 26, and 29) was separately altered to aspartic acid (D). In one case, a gla26V mutation ([gla26V]r-PC) was constructed because a patient with this particular substitution in coagulation factor IX had been previously identified. Two additional r-PC mutants were generated, viz, an r PC variant containing a substitution at arginine (R) 15 ([R15]r-PC), because this particular R residue is conserved in all gla-containing blood coagulation proteins, as well as a variant r-PC with substitution of an E at position 32 ([F31L, Q32E]r-PC), because gla residues are found in other proteins at this sequence location. This latter protein did undergo gamma-carboxylation at the newly inserted E32 position. For each of the 11 recombinant variants, a subpopulation of PC molecules that were gamma-carboxylated at all nonmutated gla precursor E residues has been purified by anion exchange chromatography and, where necessary, affinity chromatography on an antihuman PC column. The r-PC muteins were converted to their respective r-APC forms and assayed for their amidolytic activities and Ca(2+)-dependent anticoagulant properties. While no significant differences were found between wild-type (wt) r-APC and r-APC mutants in the amidolytic assays, lack of a single gla residue at any of the following locations, viz, 7, 16, 20, or 26, led to virtual complete disappearance of the Ca(2+)-dependent anticoagulant activity of the relevant r-APC mutant, as compared with its wt counterpart. On the other hand, single eliminations of any of the gla residues located at positions 6, 14, or 19 of r-APC resulted in variant recombinant molecules with substantial anticoagulant activity (80% to 92%), relative to wtr-APC. Mutation of gla residues at positions 25 and 29 resulted in r-APC variants with significant but low (24% and 9% of wtr-APC, respectively) levels of anticoagulant activity. The variant, [R15L]r-APC, possessed only 19% of the anticoagulant activity of wrt-APC, while inclusion of gla at position 32 in the variant, [F31L, Q32gla]r-APC, resulted in a recombinant enzyme with an anticoagulant activity equivalent to that of wtr-APC. PMID- 1498335 TI - Role of plasma viscosity in platelet adhesion. AB - Platelet adhesion to the vessel wall is initiated by transport of blood platelets from the bulk flow to the wall. The process of diffusion and convection of the platelets is affected by rheological conditions such as well shear rate, red blood cell (RBC) deformability, and viscosity of the medium. To study the effect of plasma viscosity on platelet adhesion, perfusion experiments with a rectangular perfusion chamber were performed. Reconstituted blood, consisting of washed platelets and washed RBCs, was circulated through this chamber for 5 minutes at a wall shear rate of 300 s-1. Different albumin concentrations were made, to obtain different medium viscosities (0.89 to 1.85 mPa.s). Platelet adhesion decreased with increasing medium viscosity up to viscosities of 0.95 mPa.s, but increased with medium viscosity above this value. Instead of human albumin solution, different plasma viscosities were obtained by dilution of Waldenstrom plasma with buffer. Plasma was depleted of fibronectin, which gave a final plasma viscosity of 2.0 mPa.s, and was dialyzed against HEPES buffer and subsequently diluted with the dialysis buffer in different fractions (0.89 to 2.00 mPa.s). Perfusions were performed over a purified von Willebrand factor coating on glass, or over an endothelial cell matrix, preincubated with von Willebrand factor. With both surfaces, platelet adhesion was dependent on the plasma viscosity in a similar way: at low plasma viscosities, adhesion was decreased with increasing plasma viscosity, while at higher plasma viscosities, adhesion increased with plasma viscosity. Adhesion values at higher plasma viscosity or at higher human albumin concentrations could be explained by effects of the medium on the rigidity of the RBCs, since platelet adhesion is known to be increased by enhanced RBC rigidity. Effects of the medium on the deformability of the RBCs were measured separately with the laser diffraction method. These experiments confirmed that presence of human albumin or plasma in the measuring suspension increased the rigidity of RBCs. To prevent influence of the medium on the RBCs in perfusion experiments, the RBCs were fixated with glutaraldehyde. Perfusion experiments with fixated RBCs in plasma over a von Willebrand factor preincubated endothelial cell matrix, showed a consequent decrease in adhesion with increasing plasma viscosity, according to the diffusion theories, whereas the increase of adhesion at high plasma viscosities was lacking. This suggests that the latter effect was entirely due to increased transport of platelets by more rigid RBCs. PMID- 1498336 TI - Sustained antithrombotic activity of hirudin after its plasma clearance: comparison with heparin. AB - Thrombus extension in patients with venous thromboembolism is due to the accretion of fibrin onto existing thrombi. Extension is promoted by both circulating and thrombus-bound thrombin, which convert fibrinogen to fibrin. Heparin is an effective antithrombotic agent, but it requires continuous administration to achieve persistent inhibition of thrombus extension. Heparin is highly effective in inhibiting fluid phase thrombin, but is a relatively ineffective inhibitor of thrombus-bound thrombin. Hirudin, unlike heparin, inactivates both circulating and fibrin-bound thrombin and, therefore, has the potential to prevent thrombus extension even after a short course of treatment. The aim of this study was to evaluate the time course of the accretion of new fibrin onto preexisting rabbit jugular vein thrombi after a 3-hour infusion of saline, heparin, and hirudin. Heparin and recombinant (r)-hirudin (CGP 39399) were infused at doses that doubled the activated partial thromboplastin time (aPTT). At the end of the 3-hour infusions in rabbits treated with saline, heparin (0.75 mg/kg), or r-hirudin (1.25 mg/kg), accretion of 125I-fibrinogen was 59 +/- 5 micrograms, 34 +/- 4 micrograms, and 21 +/- 2 micrograms, respectively (heparin and r-hirudin v saline, P less than .01; r-hirudin v heparin, P less than .01). Three hours after the end of the infusions, the accreted 125I fibrinogen in the saline-, heparin-, and hirudin-treated animals was 89 +/- 6 micrograms, 51 +/- 7 micrograms, and 23 +/- 3 micrograms, respectively; 9 hours after the end of the infusions, the accreted 125I-fibrinogen was 112 +/- 9 micrograms, 82 +/- 7 micrograms, and 25 +/- 3 micrograms, respectively. aPTT and thrombin clotting time (TCT) returned to the baseline value 90 minutes after the end of heparin or r-hirudin infusion. During in vitro experiments, human fibrin clots previously incubated in human plasma containing r-hirudin did not promote fibrinopeptide A (FPA) generation when washed and then incubated in human plasma in the absence of thrombin inhibitors. This persistent inhibition of FPA production was not observed after incubation in human plasma of human plasma clots preincubated with heparin. We conclude that heparin is effective in inhibiting thrombus extension while it is present in the circulation, but that this effect is rapidly lost after its plasma clearance. In contrast, the antithrombotic activity of r-hirudin is sustained beyond its plasma clearance, presumably because of its ability to inactivate thrombus-bound thrombin. Our findings indicate that r-hirudin might be an effective antithrombotic agent even when used for short periods. PMID- 1498337 TI - Tumor necrosis factor-induced endothelial tissue factor is associated with subendothelial matrix vesicles but is not expressed on the apical surface. AB - Cultured endothelial cells can be induced by tumor necrosis factor/cachectin (TNF) and other cytokines to synthesize the procoagulant cofactor tissue factor (TF). Intact monolayers of TNF-treated endothelial cells showed only minimal TF activity. In contrast, after permeabilization of these monolayers with detergent (saponin, 0.02%), there was approximately 10- to 20-fold increase in TF-mediated, factor VIIa-dependent factor Xa formation. Extracellular matrix derived from TNF treated endothelium, prepared after removing the cells by hypotonic lysis or ammonium hydroxide (0.1 N), also had similarly enhanced TF activity. Incubation with a blocking monoclonal antibody to TF inhibited the procoagulant activity of both TNF-stimulated endothelial cells, whether they were intact or permeabilized, and of their matrices. However, when the apical cell surface was pretreated with anti-TF antibody, washed, and then cells were lysed with water or permeabilized with saponin, similar augmentation of TF activity was still observed, suggesting the presence of a pool of TF to which the antibody did not initially gain access. Consistent with this concept, the presence of TF in the matrix of TNF-treated endothelial cells was shown by immunoblotting and morphologic studies; cultured endothelial monolayers and the native endothelium of aortic segments after exposure to TNF showed TF in extracellular matrix, associated with vesicles. In contrast, TF was virtually undetectable on the apical endothelial surface. Taken together, these findings suggest that endothelial TF can be present in a cryptic pool that only gains access to the blood after alteration in the integrity of the endothelial monolayer. PMID- 1498339 TI - Shear rate-dependent impairment of thrombus growth on collagen in nonanticoagulated blood from patients with von Willebrand disease and hemophilia A. AB - Thrombus formation on collagen fibrils was quantified at venous (100/s) and arterial (650/s and 2,600/s) wall shear rates in blood from patients with various subtypes of von Willebrand disease (vWD) and with hemophilia A (HA). Nonanticoagulated blood was drawn directly from an antecubital vein over purified type III collagen fibrils exposed in parallel-plate perfusion chambers. Blood collagen interactions were differentiated and quantified by morphometry as platelet adhesion, thrombus height, thrombus volume, and deposition of fibrin strands. Sixteen patients with vWD, including four type III, six type I, four type IIA, and two type IIB, were compared with 26 normal subjects and nine patients with HA, including six severe HA and three mild HA. Platelet adhesion and thrombus formation at 2,600/s were significantly decreased in blood from patients with vWD type III, IIA, and IIB, but not in blood from patients with type I and in HA. The abnormal thrombus formation was apparently not related to the decreased levels of factor VIII (F.VIII), because thrombus height and volume were normal in severe and mild HA. Thrombus formation at 650/s was also significantly decreased in patients with vWD type III, IIA, and IIB and slightly reduced in type I. Significant reduction in thrombus volume and height was also observed in blood from patients with severe HA, but not in mild HA. Thrombus dimensions were not affected at 100/s in the vWD subtypes. However, significantly decreased thrombus height and virtually absent fibrin deposition were observed in blood from patients with severe HA. Apparently, F.VIII supports thrombus formation at low and intermediate shear conditions, presumably through the generation of thrombin. In contrast, von Willebrand factor (vWF) mediates not only platelet adhesion, but also thrombus formation at intermediate and high shear rates. Thus, the relative contribution of coagulation (F.VIII) and platelet function (vWF) in thrombus formation appears to be shear rate dependent, but having optimal effects at different shear conditions. PMID- 1498338 TI - Relationship of antiphospholipid antibodies to pregnancy loss in patients with systemic lupus erythematosus: a cross-sectional study. AB - To determine whether an association exists between the presence of antiphospholipid antibodies and pregnancy loss, a cross-sectional study was performed. Consecutive women who were referred to three outpatient rheumatology clinics and who had systemic lupus erythematosus (SLE) and a history of one or more pregnancies were evaluated. Patients were interviewed to determine outcomes of all previous pregnancies. Blood was taken on two separate occasions at least 3 months apart to test for the presence of the lupus anticoagulant and anticardiolipin antibodies; on both occasions, five tests of the lupus anticoagulant, with well-defined normal ranges, and an enzyme-linked immunosorbent assay to measure IgG anticardiolipin antibodies were performed. Patients were considered to be positive for the lupus anticoagulant if one or more tests was abnormal on both occasions and positive for anticardiolipin antibodies if the test was abnormal on both occasions. Forty-two women were studied. Statistically significant associations were shown between lupus anticoagulant positivity and previous pregnancy loss (odds ratio [OR], 4.8; 95% confidence intervals [CI], 1.0 to 23.6; P = .05) and between anticardiolipin antibody positivity and previous pregnancy loss (OR, 20.0; 95% CI, 1.3 to 97.0; P = .01). All seven women with multiple episodes of pregnancy loss were lupus anticoagulant positive and four of these were also anticardiolipin antibody positive. If patients who are transiently positive for lupus anticoagulant and/or anticardiolipin antibodies are considered to be test positive, the associations with pregnancy loss are no longer statistically significant. Within the group of lupus anticoagulant-positive patients, we observed stronger associations between the presence of six or more positive tests and pregnancy loss than between the presence of two to five positive tests and pregnancy loss. No single test for the lupus anticoagulant provides a statistically significant association with pregnancy loss. The results of our study show that by performing multiple lupus anticoagulant tests and by repeating testing for lupus anticoagulant and anticardiolipin antibodies on more than one occasion, significant associations between the presence of antiphospholipid antibodies and previous pregnancy loss can be shown in patients with SLE. PMID- 1498340 TI - A simple method for the quantitative evaluation of neuromuscular blockade in mice. AB - The purpose of this study was to develop a simple and noninvasive method for the quantitative evaluation of neuromuscular blockade in mice. The sciatic nerve in anesthetized animals (etomidate, 50 mg/kg or mephenesin, 250 mg/kg) was stimulated using transcutaneous electrodes; repetitive supramaximal stimulations (3 Hz during 3.3 sec) were applied each minute until recovery or death occurred. Evoked action potentials of the gastrocnemius muscle were recorded. The effect of each pharmacological agent was expressed as the ratio (S5/S1) of the area of the fifth response (S5) to the first one (S1). The performance of the method was tested using neuromuscular blocking agents such as alcuronium, suxamethonium, or alpha-bungarotoxin. It was concluded that the method exhibits the required statistical performances (sensitivity, repeatability, and specificity) to be recommended for in vivo investigation of neuromuscular impairment. PMID- 1498341 TI - Antipyrine as a dialyzable reference to correct differences in efficiency among and within sampling devices during in vivo microdialysis. AB - Antipyrine was investigated as a dialyzable substance that could be used to quantitate relative differences in the efficiency of dialysis among multiple microdialysis probes and by a single probe over time. The contribution of effective membrane surface area to recovery variability was tested by the introduction of air into microdialysis probes. Reduction of effective membrane surface area reduced antipyrine recovery. Dialysates from probes implanted in the jugular vein, brain, and liver of rats receiving antipyrine demonstrated differences in antipyrine concentration among probes within the same rat. These results suggest dissimilar efficiencies of the probes to recover antipyrine, which should be uniformly distributed throughout body water. Dialysates from blood, brain, and liver probes in rats that received both antipyrine and tritiated water (3H2O) showed differences in antipyrine and 3H2O concentrations among probes. Variability of antipyrine and 3H2O concentrations over time within a probe were positively correlated, suggesting that the cause(s) of temporal variability affected both of these markers of body water. Correction of antipyrine tissue/blood ratios, using 3H2O blood/tissue ratios from the same sampling period, reduced the variability in antipyrine tissue/blood ratios, producing ratios closer to the expected value of 1. Differences in probe efficiency contributing to the variability of antipyrine and 3H2O recovery would also be expected to influence the recovery of other substances during microdialysis. The administration of antipyrine during microdialysis experiments is suggested to enable reduction of temporal and site-related differences in substance recovery that are due to differences in probe efficiency. Other methods are necessary to determine the actual extracellular concentration of dialyzed substances and the integrity of the blood-brain barrier. PMID- 1498342 TI - Techniques for drug delivery to the airways, and the assessment of lung function in animal models. AB - A common approach to understanding the mechanisms underlying clinical asthma and in new drug development is to mimic the disease in animal models. When developing animal models of pulmonary diseases, such as asthma, the experimentally induced disease may be characterized in terms of pathophysiological changes induced (e.g., inflammation, smooth muscle contraction) or by the indices of lung function that are effected by such changes. Similarly, the effects of drugs can be assessed in terms of the reversal of disease- or mediator-induced changes in lung function. Small animals, such as the guinea pig and rat, are commonly used for the assessment of lung function in models of pulmonary diseases, such as asthma, and to evaluate the effects of drugs. A variety of techniques, differing in their level of sophistication, has been developed to measure parameters of lung function in small laboratory animals. Simple techniques involve the visual assessment of the response of a conscious animal to bronchoconstriction induced by an inhaled spasmogen or antigen. This technique is rapid but gives results that are difficult to interpret in physiological terms. Bronchospasm can be better assessed in anesthetized, mechanically ventilated animals by recording bronchial tone as changes in either 1) ventilation circuit pressure or 2) air overflow as the lungs are inflated. These techniques are widely used but because they require surgical intervention they are not suited to long-term or repeat studies. In addition, they give only a limited indication of the physiological changes that affect airway caliber. To improve the models available, researchers have subsequently developed techniques that use the same physiological principles as some of the tests applied to the assessment of lung function in humans. These techniques allow the measurement of parameters of respiratory mechanics, such as lung compliance and airway resistance, that determine the relationship between pulmonary pressure changes and air flow into and out of the lungs. Continued development has resulted in models that use nonsurgical plethysmographic techniques. These allow the long-term or repeated measurement of lung function in conscious animals under minimal restraint. In the treatment of asthma, inhalation is the preferred route of administration of a drug as it allows rapid drug delivery to the site of action. Systemic effects are reduced, and the therapeutic dose is minimized. Drugs are generally inhaled as either nebulized liquids or dry powder formulations. Because drug inhalation requires patient cooperation, techniques have been modified to allow drug delivery to the airways of experimental animals.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1498343 TI - The pathogenesis of DOCA-salt hypertension. AB - Deoxycorticosterone acetate (DOCA) is an agent commonly used to induce hypertension in experimental animals. This form of hypertension is dependent on altered regulation of central pressor mechanisms including the brain renin angiotensin system. Additionally, there are characteristic changes involving the cardiovascular system and baroreflex responses. This review will discuss aspects of the pathogenesis of DOCA hypertension and the effect of various antihypertensive agents on the development of this form of hypertension. PMID- 1498344 TI - Measurement of cardiac left ventricular pressure in conscious rats using a fluid filled catheter. AB - A fluid-filled catheter consisting of 100 cm of PE50 polyethylene tubing welded to 7 cm of PE10 polyethylene tubing (PE50/PE10) was constructed for the purpose of measuring the rate of left ventricular pressure development (+dP/dt) in conscious, freely moving rats. Prior to in vivo experiments, four PE50/PE10 catheters were randomly selected, and their natural frequencies and damping ratios were determined using a square wave impact. The mean (n = 4), natural frequency of these catheters was shown to be 35.0 +/- 5.5 Hz, and the mean damping ratio was 0.83 +/- 0.10. Natural frequency plotted against increasing PE50 tubing length was shown to have a slope of -0.44 Hz/cm with a correlation coefficient of 0.99. The effect of the 7-cm PE10 tubing segment on the catheter damping ratio was also demonstrated. One of the four PE50/PE10 type catheters exhibited a damping ratio of 0.74 +/- 0.09. When the 7-cm PE10 tube was removed, the damping ratio was reduced to 0.31 +/- 0.04. Left ventricular +dP/dt obtained in conscious rats with a PE50/PE10 catheter (n = 7; 6300 +/- 300 mmHg/sec) was significantly less than the +dP/dt obtained using a 100-cm PE50 catheter (n = 6; 9400 +/- 400 mmHg/sec). The results of this study make it clear that the PE50/PE10 catheter is suitable for the measurement of left ventricular +dP/dt in the conscious rat, and that catheter design has a profound influence on both the catheter natural frequency and damping ratio. PMID- 1498345 TI - Chronic intrathecal catheterization in the sheep. AB - This paper describes a relatively simple and noninvasive method for the chronic implantation of intrathecal catheters in the sheep. The technique has been carried out on 17 occasions in nine sheep, with 60% of attempted catheterizations producing a correctly positioned, functional catheter. The placement and integrity of the catheters were confirmed by radiography using a contrast medium. Correctly placed catheters have been maintained for up to 16 months without problems. PMID- 1498346 TI - Epicardial His bundle recordings in the guinea pig in vivo. AB - In small animals, His bundle activity is commonly registered using intracavitary electrodes in Langendorff-perfused hearts. The present study evaluates the feasibility of epicardial registration of His bundle activity in 30 guinea pigs in vivo, anesthetized with 60 mg/kg sodium pentobarbital i.p. Following median sternotomy, a bipolar electrode, mounted on a flexible stand, was placed into the aortic-right atrial groove. His bundle activity was easily detected in all animals. Mean PA, AH, and HV intervals were 16.7 +/- 1.4 msec (range: 6.0-34.0 ms), 36.4 +/- 1.5 ms (range: 22.0-54.0 msec) and 14.4 +/- 0.4 msec (range: 9.0-20 msec), respectively. Administration of verapamil and vagal stimulation induced significant prolongations of AH intervals without affecting HV intervals; lidocaine prolonged both AH and HV intervals. Both at baseline and following drug administration there was excellent agreement between the AH and HV intervals assessed from simultaneously registered epicardial and endocardial His bundle electrograms (n = 12). The presented model provides reproducible values for atrioventricular (AV) nodal and His-to-ventricular conduction intervals in the guinea-pig in vivo and will, thus, be a valuable tool in electrophysiologic drug evaluation. PMID- 1498347 TI - Technique of reflection electron microscopy. AB - Details of the technique of reflection electron microscopy (REM) are described. Step by step instruction is given on how to do it on an ordinary electron microscope. Also given are some specimen preparation techniques and strategy of REM investigation. PMID- 1498348 TI - Recent studies of surface dynamic processes by reflection electron microscopy. AB - Reflection electron microscope studies of surface dynamic processes are reviewed and illustrated with recent new observations. They include: surface electromigration and current dependent structures of Si surfaces; surface etching by oxidation of Si surface; and growth of two dimensional alloyed adsorbate by co deposition of metals on Si surface. The observations revealed details of the surface dynamic processes, which are difficult to obtain with other surface analysis techniques. PMID- 1498349 TI - Application of ultrahigh vacuum reflection electron microscopy for the study of clean silicon surfaces in sublimation, epitaxy, and phase transitions. AB - The construction and performance of an ultrahigh vacuum reflection electron microscope (UHV REM) on the base of a transmission electron microscope with top entry stage are described. Some results of in situ study of structural transformations on clean silicon surfaces during sublimation, surface phase transitions, and initial stages of epitaxial growth are shown. PMID- 1498351 TI - Bloch wave treatment of symmetry and multiple beam cases in reflection high energy electron diffraction and reflection electron microscopy. AB - Bloch wave equations for the multiple beam cases in reflection high energy electron diffraction (RHEED) are derived from the integral equation by forward- and back-scattering Green function operators. A linearization is achieved through separation in a forward- and a back-scattering component for each beam. This leads to a set of fundamental equations similar to the transmission case, but with a non-Hermitian matrix, and the beams may be entered as either forward-, back-scattered, or both. The number of beams needed to be included in RHEED calculations is thus reduced, and so are the computing time and computer space required. The systematic row case, corresponding to reflections from planes parallel to the crystal surface, is treated in detail and illustrated by calculations of dispersion surfaces and rocking curves for Au(001). Symmetry relations for the systematic row and between reciprocal rows are discussed and illustrated. PMID- 1498350 TI - Degradation, amorphization, and recrystallization of ion bombarded Si(111) surfaces studied by in situ reflection electron microscopy and reflection high energy electron diffraction techniques. AB - In this paper we report the effect of noble gas ions bombardment on the degradation of atomically flat Si(111) surfaces at room and high (400 degrees C 600 degrees C) temperatures. Reflection high energy electron diffraction (RHEED) and reflection electron microscopy (REM) have been used to characterize the topography and structure of the as-implanted and post annealed surface layers. It is shown that the fading of the specularly reflected beam is not directly related to the amorphization of the surface. This experimental study has also evidenced the difficulties one meets to regrow a defect-free material after amorphization by noble gas bombardment. For high temperature for which the amorphization is not possible, the surface loses its stepped structure and turns into a monocrystalline but atomically rough surface. This roughness is a function of substrate temperature. PMID- 1498352 TI - Developments in the dynamical theory of high energy electron reflection. AB - High energy electron reflection (HEER) is an important technique in surface science and uses the information carried by high energy electrons reflected from surfaces to study surface structures and surface electronic states. With the development of reflection high energy electron diffraction (RHEED), high energy electron microscopy (REM), and high energy electron energy loss spectroscopy (EEL) in surface science, the usefulness of HEER has been widely recognized and demonstrated. However, a stationary dynamical solution for an arbitrary surface for HEER has not been obtained yet. In this paper, some developments in understanding the dynamical theory of HEER, particularly in recent years, are reviewed: 1. The introduction of the concept of current flow for a semi-infinite crystal model has removed the confusion around the wave points in the "band gap." 2. The consistency between the Bloch wave and multislice in the Bragg case has verified the validity of the argument of current flow and led to the emergence of the BMCR method (Bloch wave + Multislice Combined for Reflection). 3. The failure of the Bloch Wave-Only solution (the BWO solution) on Au (110) surfaces in the Bragg case revealed by the BMCR method implies that previous BWO calculations in the Bragg case might be at fault. 4. The 2-D dependence of the electron wave fields and Picard iteration-like character of multislice calculation in the Bragg case has led to the emergence of an Edge Patching method in Multislice-mode-Only (the EPMO method). The new method yields an infinitely convergent stationary dynamical solution for an arbitrary surface. PMID- 1498354 TI - Observation of atomic steps on single crystal surfaces by a commercial scanning electron microscope. AB - Atomic steps on (111) and (100) crystal surfaces of Pt were observed using a commercial scanning electron microscope (SEM) in secondary electron mode. By comparing the SEM images and those by reflection electron microscopy (REM), the observed contrast was confirmed to be that from atomic steps on crystal surfaces. The contrast mechanism is briefly discussed. One application of this imaging technique is also shown. PMID- 1498353 TI - Reflection electron energy-loss spectroscopy and imaging for surface studies in transmission electron microscopes. AB - A review is given on the techniques and applications of high-energy reflection electron energy-loss spectroscopy (REELS) and reflection electron microscopy (REM) for surface studies in scanning transmission electron microscopes (STEM) and conventional transmission electron microscopes (TEM). A diffraction method is introduced to identify a surface orientation in the geometry of REM. The surface dielectric response theory is presented and applied for studying alpha-alumina surfaces. Domains of the alpha-alumina (012) surface initially terminated with oxygen can be reduced by an intense electron beam to produce Al metal; the resistance to beam damage of surface domains initially terminated with Al+3 ions is attributed to the screening effect of adsorbed oxygen. Surface energy-loss near-edge structure (ELNES), extended energy-loss fine structure (EXELFS), and microanalysis using REELS are illustrated based on the studies of TiO2 and MgO. Effects of surface resonances (or channeling) on the REELS signal-to-background ratio are described. The REELS detection of a monolayer of oxygen adsorption on diamond (111) surfaces is reported. It is shown that phase contrast REM image content can be significantly increased with the use of a field emission gun (FEG). Phase contrast effects close to the core of a screw dislocation are discussed and the associated Fresnel fringes around a surface step are observed. Finally, an in situ REM experiment is described for studying atomic desorption and diffusion processes on alpha-alumina surfaces at temperatures of 1,300-1,400 degrees C. PMID- 1498355 TI - Observation of double line contrast in surface imaging. AB - The double line contrast of a single-atom height step observed in surface imaging for a single crystal in reflection electron microscopy is studied under a variety of experimental conditions. It is suggested that this abnormal contrast is directly associated with the dynamical electron diffraction process. The behavior of the double line contrast is closely related to the order of the Bragg reflected beam, and can be observed mostly under one of the two commonly cited resonance conditions. This phenomenon clearly reveals the differences in the surface imaging for various resonance conditions. PMID- 1498356 TI - Preparation and characterization of MgO surfaces by reflection electron microscopy. AB - We have employed several different methods to prepare (100) and (111) surfaces of MgO crystals. (100) surfaces prepared by simple cleaving give good reflection high energy electron diffraction (RHEED) patterns and surfaces with a high density of coarse steps. Chemical polishing of this surface results in a roughening of the topography whilst annealing in oxygen considerably smoothens the surfaces although they appear to be contaminated. Under certain conditions we find that the MgO crystals will cleave along the (111) plane. Both cleaved and mechanically polished (111) surfaces are atomically flat and reconstructed after oxygen annealing. PMID- 1498357 TI - Characterization of the annealed (0001) surface of sapphire (alpha-Al2O3) and interaction with silver by reflection electron microscopy and scanning reflection electron microscopy. AB - Annealed (0001) surfaces of single-crystal sapphire (alpha-Al2O3) rod have been studied in the electron microscope using reflection electron microscopy (REM), scanning reflection electron microscopy (SREM), and reflection high energy electron diffraction (RHEED). Annealed surfaces of (0001) sapphire are vicinal and characterized by close-packed (0001)-oriented terraces separated by faceted multiple-height steps, with edges parallel to energetically preferred low-index directions (less than 1010 greater than and less than 1120 greater than). These structural features are not seen on cleaved surfaces or polished surfaces treated at temperatures less than 1,250 degrees C. Oxygen-annealing produces clean surfaces which prove useful for investigating the interaction of deposited metals with the (0001) sapphire. Both REM and SREM (with microdiffraction spots) techniques have been used to observe fine structure of flat Ag islands on the scale of 1-100 nm on the (0001)-oriented terraces as well as aggregations at the steps. A preliminary result on interaction with Cu is also included. PMID- 1498358 TI - Reflection electron microscopy and interferometry of atomic steps on gold and platinum single crystal surfaces. AB - Two beam interferences produced using an electrostatic biprism, which is inserted in the position of the selected area diaphragm of a commercial electron microscope, may be used in reflection electron microscopy to determine the phase shifts induced by structures on single crystal surfaces. A description of our interferometrical and holographical experiments on the phase shift at steps on (111)Au and (111)Pt single crystal surfaces is given and a straight forward interpretation of the results in terms of refraction will be discussed. As a particular result phase shifts of pi and 0.9 pi were measured for monatomic steps on (111)gold and (111)platinum surfaces, respectively. PMID- 1498359 TI - Observation of surfaces by reflection electron holography. AB - Reflection electron holography is described as a method to observe sub-A surface morphology. Phase shift of a Bragg-reflected electron wave was measured by means of holographic interferometry using an electron microscope equipped with a field emission electron gun and an electron biprism. A short wavelength of high energy electrons is the essential key to the high vertical sensitivity of this method, since geometrical path differences produced by the surface topography are measured in units of wavelengths in interferometrical measuring. Phase shift at a monoatomic step and the displacement field around a dislocation emerging on the surface were observed. PMID- 1498360 TI - Ideas are becoming an endangered species. PMID- 1498361 TI - SpCoel1: a sea urchin profilin gene expressed specifically in coelomocytes in response to injury. AB - SpCoel1 is a single copy gene that is specifically expressed in most of the coelomocytes of the adult purple sea urchin, Strongylocentrotus purpuratus. The 4 kb transcript from this gene has a relatively short (426 nucleotide) open reading frame (ORF) with long 3' and 5' untranslated regions. The ORF encodes a protein that has strong amino acid sequence similarity to profilins from yeast to mammals. Transcript titrations of SpCoel1 show significant increases per coelomocyte in animals that have been physiologically challenged. Increases in transcript levels are of similar magnitudes between animals receiving different treatments, such as injuries from needle punctures or from injections of foreign cells. The evidence presented here implies a molecular mechanism by which this lower deuterostome defense system responds to external insult, viz that an external "injury signal" activates a signal transduction system, which in turn mediates the alterations in cytoskeletal state that are required for coelomocyte activation. PMID- 1498362 TI - Alternative pathways for the sorting of soluble vacuolar proteins in yeast: a vps35 null mutant missorts and secretes only a subset of vacuolar hydrolases. AB - vps35 mutants of Saccharomyces cerevisiae exhibit severe defects in the localization of carboxypeptidase Y, a soluble vacuolar hydrolase. We have cloned the wild-type VPS35 gene by complementation of the vacuolar protein sorting defect exhibited by the vps35-17 mutant. Sequence analysis revealed an open reading frame predicted to encode a protein of 937 amino acids that lacks any obvious hydrophobic domains. Subcellular fractionation studies indicated that 80% of Vps35p peripherally associates with a membranous particulate cell fraction. The association of Vps35p with this fraction appears to be saturable; when overproduced, the vast majority of Vps35p remains in a soluble fraction. Disruption of the VPS35 gene demonstrated that it is not essential for yeast cell growth. However, the null allele of VPS35 results in a differential defect in the sorting of vacuolar carboxypeptidase Y (CPY), proteinase A (PrA), proteinase B (PrB), and alkaline phosphatase (ALP). proCPY was quantitatively missorted and secreted by delta vps35 cells, whereas almost all of proPrA, proPrB, and proALP were retained within the cell and converted to their mature forms, indicating delivery to the vacuole. Based on these observations, we propose that alternative pathways exist for the sorting and/or delivery of proteins to the vacuole. PMID- 1498363 TI - Actin- and tubulin-dependent functions during Saccharomyces cerevisiae mating projection formation. AB - Several conditional-lethal mutant alleles of the single-copy Saccharomyces cerevisiae beta-tubulin and actin genes were used to evaluate the roles of microtubules and actin filaments in the pheromone-induced extension of mating projections. Mutants defective in tubulin assembly form projections indistinguishable in appearance from those formed by wild-type cells. However, the tubulin mutants are unable to move their nuclei into the projections and to orient the spindle pole body associated with each nucleus toward the projection tip. Actin mutants are defective in spatial orientation of cell-surface growth required for formation of normal mating projections. Migration of nuclei into mating projections and Spa2p segregation to projection tips are also defective in actin mutants. Studies with abp1 null mutants showed that the function of the Abp1p actin-binding protein is either not required for projection formation or there are other proteins in yeast with similar functions. Our findings demonstrate that actin is required to restrict cell-surface growth to a defined region for pheromone-induced morphogenesis and suggest that nuclear position and orientation in mating projections depend on direct or indirect interaction of microtubules with actin filaments. PMID- 1498364 TI - Phosphorylation of FAR1 in response to alpha-factor: a possible requirement for cell-cycle arrest. AB - Exposure of yeast a cells to alpha-factor causes cells to arrest in the G1 phase of the cell cycle. The FAR1 gene is required for this cell-cycle arrest; its product is necessary for the inhibition of a G1 cyclin, CLN2. Earlier work demonstrated that alpha-factor caused an increase in the transcription of FAR1 severalfold over a measurable basal level. We now show that transcriptional induction of FAR1 from a heterologous promoter is not sufficient to inhibit CLN2 in the absence of alpha-factor. We also show that FAR1 is phosphorylated in response to alpha-factor and propose that this phosphorylation may be required for FAR1 activity. PMID- 1498365 TI - Membrane potential modulates release of tumor necrosis factor in lipopolysaccharide-stimulated mouse macrophages. AB - Lipopolysaccharide (LPS)-mediated synthesis of macrophage gene products such as tumor necrosis factor (TNF) is controlled by different signaling pathways. We investigated intracellular free Ca2+ (Ca2+ic) and the membrane potential as early cellular responses to LPS and their role in the synthesis and release of TNF. In peritoneal macrophages and in the RAW 269 mouse macrophage cell line, LPS and its biologically active moiety lipid A stimulated TNF synthesis but exerted no significant effects on these early cellular responses using Fura-2/Indo-1 to measure Ca2+ic and bis-oxonol, as well as the patch-clamp technique to monitor membrane potential. In contrast, the platelet-activating factor transiently induced both an increase in Ca2+ic and cell membrane depolarization but no significant TNF release. Increased extracellular K+ concentrations or K(+) channel blockers, such as quinine, tetraethylammonium, or barium chloride, inhibited the LPS-stimulated release of TNF alpha, as well as the accumulation of cell-associated TNF alpha as found by enzyme-linked immunosorbent assay analysis, but did not inhibit TNF alpha mRNA accumulation. Concentrations of quinine (greater than 125 microM) or of enhanced extracellular K+ (25-85 mM) required to inhibit TNF production both significantly depolarized macrophages. These results indicate a lack of ion transport activities as early cellular responses of macrophages to LPS but suggest an important regulatory role of the membrane potential on the posttranscriptional synthesis and release of TNF in macrophages. PMID- 1498366 TI - tra-2 encodes a membrane protein and may mediate cell communication in the Caenorhabditis elegans sex determination pathway. AB - The Caenorhabditis elegans sex-determining gene, tra-2, promotes female development in XX animals. In this paper we report the cDNA sequence corresponding to a 4.7 kb tra-2 mRNA and show that it is composed of 23 exons, is trans-spliced to SL2, and contains a perfect direct repeat in the 3' untranslated region. This mRNA is predicted to encode a 1475 amino acid protein, named pTra2A, that has a secretory signal and several potential membrane-spanning domains. The molecular analysis of tra-2 loss-of-function mutations supports our open reading frame identification and suggests that the carboxy-terminal domain is important for tra-2 activity. We propose that in XX animals the carboxy-terminal domain of pTra2A negatively regulates the downstream male promoting fem genes. In XO animals, tra-2 is negatively regulated by her-1, which acts cell nonautonomously. Because hydropathy predictions suggest that pTra2A is an integral membrane protein, pTra2A might act as a receptor for the her-1 protein. We propose that in XO animals, the her-1 protein promotes male development by binding and inactivating pTra2A. The role of cell communication in C. elegans sex determination might be to ensure unified sexual development throughout the animal. If so, then regulation of sexual fate by her-1 and tra-2 might provide a general model for the coordination of groups of cells to follow a single cell fate. PMID- 1498367 TI - Molecular signal integration. Interplay between serine, threonine, and tyrosine phosphorylation. PMID- 1498368 TI - A histone variant, H2AvD, is essential in Drosophila melanogaster. AB - H2AvD, a Drosophila melanogaster histone variant of the H2A.Z class, is encoded by a single copy gene in the 97CD region of the polytene chromosomes. Northern analysis shows that the transcript is expressed in adult females and is abundant throughout the first 12 h of embryogenesis but then decreases. The H2AvD protein is present at essentially constant levels in all developmental stages. Using D. melanogaster stocks with deletions in the 97CD region, we have localized the H2AvD gene to the 97D1-9 interval. A lethal mutation in this interval, l(3)810, exhibits a 311-base pair deletion in the H2AvD gene, which removes the second exon. P-element mediated transformation using a 4.1-kilobase fragment containing the H2AvD gene rescues the lethal phenotype. H2AvD is therefore both essential and continuously present, suggesting a requirement for its utilization, either to provide an alternative capability for nucleosome assembly or to generate an alternative nucleosome structure. PMID- 1498369 TI - Sec23p and a novel 105-kDa protein function as a multimeric complex to promote vesicle budding and protein transport from the endoplasmic reticulum. AB - A cell-free protein transport reaction has been used to monitor the purification of a functional form of the Sec23 protein, a SEC gene product required for the formation or stability of protein transport vesicles that bud from the endoplasmic reticulum (ER). Previously, we reported that Sec23p is an 84-kDa peripheral membrane protein that is released from a sedimentable fraction by vigorous mechanical agitation of yeast cells and is required for ER to Golgi transport assayed in vitro. We have purified soluble Sec23p by complementation of an in vitro ER to Golgi transport reaction reconstituted with components from sec23 mutant cells. Sec23p overproduced in yeast exists in two forms: a monomeric species and a species that behaves as a 250- to 300-kDa complex that contains Sec23p and a distinct 105-kDa polypeptide (p105). Sec23p purified from cells containing one SEC23 gene exists solely in the large multimeric form. A stable association between Sec23p and p105 is confirmed by cofractionation of the two proteins throughout the purification. p105 is a novel yeast protein involved in ER to Golgi transport. Like Sec23p, it is required for vesicle budding from the ER because p105 antiserum completely inhibits transport vesicle formation in vitro. PMID- 1498371 TI - Optimization of a model of full-thickness epidermal burns in the pig and immunohistochemical study of epidermodermal junction regeneration during burn healing. AB - In order to obtain a wound model in which healing involved epidermis rebuilding and epidermodermal junction (EDJ) regeneration without involvement of any dermal repair, we optimized a previous model of experimental cutaneous burning with an aluminum bar by testing various conditions of burning associated with different pre- and postburn skin treatments. On the optimized model of full-thickness epidermal burns without any dermal injury, we investigated the kinetics of regeneration of 4 EDJ components, from day 2 to day 23 after burning. The epidermal healing was studied by light microscopy and EDJ regeneration by indirect immunofluorescence with one bullous pemphigoid (BP) serum, antisera to fibronectin and to type IV collagen (Coll IV) and the monoclonal antibody 4C 12-8 to laminin. Histologically, neoepidermis, detected from day 2, appeared as a reepidermization tongue which progressed from the burn edges between the overlying necrotic burned epidermis and the underlying uninjured dermis. Epidermis continuity was found to be restored at day 9. Immunohistochemically, labelling of BP antigen (BPA), Coll IV and laminin extended all along the neo EDJ, from day 2 to day 23. In contrast, fibronectin labelling was detected only in the proximal and median portions of the neo-EDJ before day 7, then all along the neo-EDJ, from day 7 to day 23. For all the components except Coll IV, the intensity of the labelling beneath the neoepidermis was higher than that of the residual labelling remaining under the necrotic epidermis. Therefore, BPA and laminin regenerated synchronously to neoepidermis whereas fibronectin first regenerated with delay, then synchronously.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1498370 TI - A novel transcriptional enhancer is involved in the prolactin- and extracellular matrix-dependent regulation of beta-casein gene expression. AB - Lactogenic hormones and extracellular matrix (ECM) act synergistically to regulate beta-casein expression in culture. We have developed a functional subpopulation of the mouse mammary epithelial cell strain COMMA-1D (designated CID 9), which expresses high level of beta-casein, forms alveolar-like structures when plated onto the EHS tumor-derived matrix, and secretes beta-casein unidirectionally into a lumen. We have further shown that ECM- and prolactin dependent regulations of beta-casein occur mainly at the transcriptional level and that 5' sequences play an important role in these regulations. To address the question of the nature of the DNA sequence requirements for such regulation, we analyzed the bovine beta-casein gene promoter in these cells. We now have located a 160-bp transcriptional enhancer (BCE1) within the 5' flanking region of the beta-casein gene. Using functional assays, we show that BCE1 contains responsive elements for prolactin- and ECM-dependent regulation. BCE1 placed upstream of a truncated and inactive beta-casein promoter (the shortest extending from -89 to +42 bp with regard to the transcription start site) reconstitutes a promoter even more potent than the intact promoter, which contains BCE1 in its normal context more than 1.5 kb upstream. This small fusion promoter also reconstitutes the normal pattern of regulation, including a requirement for both prolactin and ECM and a synergistic action of prolactin and hydrocortisone. By replacing the milk promoter with a heterologous viral promoter, we show that BCE1 participates in the prolactin- and ECM-mediated regulation. PMID- 1498372 TI - Photochemotherapy with topical khellin and sunlight in vitiligo. AB - In order to evaluate the efficacy of topical khellin the vitiligo macules of one side only were painted in 41 patients with a 2% solution of khellin in acetone and propylene glycol (90 and 10%, respectively) and exposed to sunlight for a period of 4 months with 3 weekly applications and with exposure times up to 90 min. The macules of the other side were treated in 36 of the 41 patients with acetone and propylene glycol only and sun-exposed with the same schedule, while in the remaining 5 patients they were neither treated with khellin or placebo nor sun-exposed. No significant difference was evidenced between the khellin and placebo-treated sides: no excellent result (repigmentation more than 75% of the affected area) was found, and good results (repigmentation more than 50%) were found in 24.9% of khellin- plus sunlight-treated macules and in 22.3% of placebo- plus sunlight-treated macules. PMID- 1498373 TI - Telogen effluvium due to recombinant interferon alpha-2b. AB - Five of 10 patients receiving long-term recombinant interferon alpha-2b therapy complained of considerable hair loss. The pull test and the trichogram showed a telogen count consistent with a telogen effluvium. In 2 patients the telogen count progressively improved despite continuing the treatment, whereas in 3 patients the trichogram continued to show an increased telogen count until interferon therapy was discontinued. Pohl-Pinkus hair constrictions were also present in 2 patients. PMID- 1498374 TI - Alopecia areata and interleukin-2 receptor. AB - Interleukin-2 (IL-2) is a lymphokine produced by activated T cells and its receptor (IL-2R) is expressed on T cells; one of the IL-2R components can be measured as a soluble serum protein (sIL-2R). Levels of sIL-2R were measured as a sign of T cell activation in serum of 12 patients suffering from alopecia areata (totalis or universalis) and in a group of healthy control subjects. An enzyme linked immunosorbent assay was used to determine the levels of sIL-2R in blood samples drawn during both the active and resting phase of the disease. In patients with alopecia areata in active phase the sIL-2R concentrations were significantly higher than in stable phase and in controls. The biologic role of sIL-2R is still unknown, but one could speculate that T lymphocyte activation with subsequent secretion of IL-2 and IL-2R expression may contribute to the immune inflammatory mechanism of alopecia areata. PMID- 1498375 TI - Cutaneous complications of artificial hair implantation: a pathological study. AB - Five patients who developed severe cutaneous complications after artificial hair implantation were subjected to a scalp biopsy. The pathology showed the presence of hyperplastic epidermal proliferations that produced infundibulum-like structures around the implanted fibers in the superficial dermis. A dense acute inflammatory infiltrate surrounded the artificial fibers in the superficial dermis. In the deep dermis a granulomatous infiltrate was present whereas in the hypodermis the inflammatory infiltrate was sparse and the fibers were embedded in fibroplasia. The pathology of a patient who did not present any skin inflammation after artificial hair implantation showed similar pathological features but the absence of acute inflammation suggesting that bacterial infections play a major role in the development of the cutaneous complications of hair implantation. Since definitive treatment of the infections is ineffective until the fibers are removed from the scalp, surgical treatment was required in 2 of our patients. PMID- 1498376 TI - Keratosis follicularis spinulosa decalvans: report of a case with ultrastructural study and unsuccessful trial of retinoids. AB - Keratosis follicularis spinulosa decalvans (KFSD) is a genetic disorder characterized by disseminated follicular hyperkeratosis, especially localizated to scalp and face. We report the case of a new patient displaying typical features of KFSD. Ultrastructural study was performed and displayed round keratohyalin granules in follicular keratinocytes. Trial with etretinate, which has not been reported before in this disease, proved to be ineffective. PMID- 1498377 TI - Wells' syndrome: report of 2 cases. AB - Wells' syndrome is a rare dermatological disease whose origin remains uncertain. Based on clinical, biological and etiological data, it might be recognized as a major form of urticaria. The triggering factors are numerous and unspecific. As revealed by the 51Cr-EDTA test which measures intestinal permeability, the lesions do not seem to be caused by an excess of antigens passing through the intestinal mucosa. PMID- 1498378 TI - Acute generalized exanthematic pustulosis induced by cefaclor and acetazolamide. AB - We report a case of acute generalized exanthematic pustulosis induced by 2 different drugs, cefaclor and acetazolamide. The diagnosis was confirmed by challenge tests, and these 2 drugs respectively were proven to be responsible for the patient's pustular eruptions. PMID- 1498380 TI - Melagenina and vitiligo. PMID- 1498379 TI - Systemic mastocytosis treated with histamine H1 and H2 receptor antagonists. AB - A case of systemic mastocytosis with skin characteristics of telangiectasia macularis eruptiva perstans is reported. Systemic involvement was confirmed as a combination of highly increased urinary excretion of methyl imidazole acetic acid (Melm AA) and increased amounts of mast cells in skin, liver and colon transversum. Treatment with cimetidine (H2 receptor antagonist) resulted in diarrhea, however, the addition of cyproheptadine (H1 receptor antagonist) was beneficial in amelioration of the cutaneous symptoms of mastocytosis. The excretion of Melm AA was unchanged during treatment. After 7 months of continuous cimetidine and cyproheptadine treatment no side effects were observed. PMID- 1498381 TI - Antiphospholipid antibodies and melanoma: a link? PMID- 1498382 TI - Nuchal nevus flammeus in alopecia areata. PMID- 1498383 TI - Preferential activation of the alternative pathway of complement in psoriatic lesional skin. PMID- 1498384 TI - The 'isothiazolinone story'. PMID- 1498385 TI - Is Microsporum canis infection about to become a serious dermatological problem? AB - In Europe, especially in the Mediterranean, the incidence of Microsporum canis infection has been on a steep increase during the recent years. In some countries (Italy) and geographic areas (Slovenia), M. canis is the most often isolated dermatophyte. In Slovenia (Yugoslavia), a dramatic increase in the incidence of M. canis infection has been observed recently, both in absolute figures and as compared to the rest of isolated dermatophytes. M. canis is a cause of tinea most prevalent in children. All attempts made during the past 6 years to eliminate the natural source of infection, represented mainly by stray cats, have failed. M. canis infection is becoming a serious epidemiologic problem in Europe. For its solution, integrated efforts of medical and veterinary services, and probably more stringent rules and controls in this particular area, will be required. PMID- 1498386 TI - Evaluation of the frequency of contact allergic reactions to Kathon CG in the Maastricht area--1987-1990. AB - In the period 1987-1990, 999 patients suspected of a contact allergy were patch tested with Kathon CG 100 ppm active ingredients aq. Of these patients, 84 (8.4%) showed a positive reaction (70% females). In 62% of these cases clinical relevance was established. Most of them suffered from contact dermatitis of the face, the hands or the perianal region. PMID- 1498387 TI - Sensitization to the isothiazolinone biocide. Report of the Swiss Contact Dermatitis Research Group 1988-1990. AB - The rate of sensitization to isothiazolinones (Kathon CG) detected in Switzerland rose from 3.5% (out of 2,491 patients) in 1987 to 6.3% (out of 982 patients) in 1988 and 5.6% (out of 2,295 patients) in 1989-90. This rate of sensitization appears to be related to the more and more widespread use of isothiazolinone biocide in cosmetics, domestic products and in industry. PMID- 1498388 TI - How to better understand the angry back syndrome. AB - The angry back or excited skin syndrome consists of patch test reactions that are positive only when associated with adjacent or distant inflammatory skin lesions. Recent experiments in the mouse and man have provided the knowledge on the critical role of tumor necrosis factor in contact dermatitis as well as its importance for the induction of adhesion molecules. Based on these new findings we speculate on mechanisms that might explain this poorly understood clinical phenomenon. PMID- 1498389 TI - Illusion and reality in visual observation: a trap for the unwary clinician. PMID- 1498390 TI - Optical illusions in clinical dermatology: the Mach band phenomenon and afterimages. AB - A survey of dermatologists was conducted to determine whether the perceptions of afterimages and Mach bands impacted on clinical dermatology practice. 26.5% (13/49) of respondents indicated that they perceived one or both of these optical illusions. No false-positive potassium hydroxide interpretations of skin scrapings for hyphae were reported due to perceived afterimages, and no skin biopsies were reportedly performed as a result of Mach bands. PMID- 1498391 TI - Polymorphisms of HLA class III genes in allergic contact dermatitis. AB - HLA class III polymorphisms (BF, C4A, C4B) were studied in 55 patients of different age and sex suffering from allergic contact dermatitis, with sensitization to different substances. In the overall group of patients no significant correlation between the disease and HLA markers was found. BF F allele was present in 34% and BS S in 64% of patients suffering from allergic contact dermatitis to nickel only versus 16.45% (relative risk, RR = 2.61) and 80.76% (RR = 0.42), respectively, of the control population. The BF FB subtype frequency was 23.91% versus 7.57% in the control samples (RR = 3.88). We thus hypothesize that this polymorphic serum protein might be involved in the pathogenesis of allergic contact dermatitis to nickel. PMID- 1498392 TI - Contact allergy to isothiazolinone derivatives: unusual clinical presentations. AB - Contact allergic reactions to the mixture of 5-chloro-2-methyl-4-isothiazoline-3 one and 2-methyl-4-isothiazoline-3-one are most frequently associated with intolerance to cosmetics. The present article points out that such reactions, particularly on the face, can have unusual clinical presentations that are very similar to seborrheic eczema, lupus erythematosus, lymphocytic infiltrate or photodermatitis. Atopic dermatitis is also often erroneously suspected. PMID- 1498394 TI - Pigmented dermatofibrosarcoma protuberans (Bednar tumour). AB - A case of pigmented dermatofibrosarcoma protuberans in a 37-year-old man is reported. The tumour presented as a nodular lesion located in the left scapular area. Surgical resection with wide margins was performed. No recurrences have appeared to date. The presumptive origin of this entity is briefly discussed. PMID- 1498393 TI - Treatment of atopic dermatitis by allergen-antibody complexes: long-term clinical results and evolution of IgE antibodies. AB - This study describes the long-term follow-up of the clinical response of 10 adult patients suffering from atopic dermatitis (AD) who were treated by administration of complexes made of Dermatophagoides pteronyssinus (Dpt) allergens and autologous antibodies specific to that allergen. We have already described the clinical improvement observed after 1 year of treatment involving regular injections of complexes; this improvement was maintained throughout a second year, even though the number of injections was greatly reduced. At the end of the second year of treatment, 5 patients were completely free of disease, and 3 had had a short-lasting recurrence of low-severity dermatitis. Using a disease intensity index the mean improvement for these 8 patients was 83% compared to baseline values. One patient showed a significant recurrence of symptoms, and 1 patient left the study for personal reasons when she was in good clinical condition. A significant reduction of specific anti-Dpt IgE antibody titers was observed in 7 out of the 8 patients in clinical remission, while the level of total IgE antibodies was unchanged until the very end of the study. This study not only confirms that clinical benefit can be obtained from the treatment of AD patients hypersensitive to Dpt by injections of allergen-antibody complexes but also indicates that the therapy induces a suppression of IgE antibody production that is specific for the particular allergen. PMID- 1498395 TI - Vitiligo-like depigmentation and morpheas after specific intralymphatic immunotherapy for malignant melanoma. AB - We report the case of a patient with stage 2 malignant melanoma (MM), who received a specific immunotherapy consisting of intralymphatic injections of irradiated MM cells. She developed subsequently vitiligo-like leukoderma and several plaques of localized scleroderma. Simultaneously an increase in the patient's cytotoxic activity against MM cells was detected in vitro. The responsibility of immune phenomena and specific immunotherapy for the appearance of depigmentation and morpheas is discussed. PMID- 1498396 TI - Localized scleroderma is not a Borrelia burgdorferi infection in France. PMID- 1498397 TI - Disseminated porokeratosis and myelodysplastic syndrome. PMID- 1498399 TI - Focal epithelial hyperplasia. AB - In 2 children (brother and sister) focal epithelial hyperplasia could be diagnosed by means of histology, human papillomavirus typing and Southern blot. In the 14-year-old girl the history could be followed over many years. The high familial incidence and the special geographic distribution of focal epithelial hyperplasia are pointed out. PMID- 1498398 TI - Postoperative hyperemia of the glans penis with ulcers following revascularization surgery for vascular impotence. AB - A case of postoperative hyperemia of the glans penis following revascularization surgery for erectile impotence is described. This new surgical concept (Hauri) combines arterial revascularization with an arteriovenous shunt. The so-called 'postoperative hyperemia of the glans penis' is observed in 10-20% of the cases after arterialization of the dorsal penile vein, i.e. a pure arteriovenous shunt, and in 2-3% of the cases in arterioarterial anastomoses. The ulcers of the glans penis, which occurred 1 year after the operation, healed under careful local anti inflammatory and antibiotic therapy. PMID- 1498400 TI - Congenital hypertrophy of the lateral nail folds of the hallux. AB - A case of a 7-month-old boy with bilateral symmetrical congenital hypertrophy of the lateral nail folds of the hallux is described. The body showed no other skin symptoms. The types of ingrowing nails in infancy are discussed. A partial remission of the disease after 1 year was observed. PMID- 1498401 TI - Localized unilateral hyperhidrosis. AB - We describe a case of localized unilateral hyperhidrosis on the forehead in a 52 year-old woman. The pathophysiology of this unique clinical picture and its treatment are described. PMID- 1498402 TI - Targetoid hemosiderotic hemangioma. AB - A new case of hemosiderotic targetoid hemangioma is reported. The literature is briefly reviewed. PMID- 1498403 TI - Mycetoma of the foot due to Fusarium sp. treated with oral ketoconazole. AB - We report the case of a 30-year-old Nigerian patient with mycetoma of the foot without bone involvement caused by Fusarium sp..Long-term administration of ketoconazole produced a significant improvement with good clinical and biological tolerance. PMID- 1498404 TI - Syringolymphoid hyperplasia with alopecia--a syringotropic cutaneous T-cell lymphoma? AB - Report on a 44-year-old male patient who developed a solitary plaque on the trunk. Histologically there is hypertrophy of adnexal duct structures and a lymphoid infiltrate with a T helper phenotype. The term 'syringotropic variant of mycosis fungoides' is proposed for this distinct disorder. PMID- 1498405 TI - Disseminated granuloma anulare: therapy with vitamin E topically. AB - Topical use fo vitamin E (E-Mulsin) is recommended as an alternative treatment modality in otherwise recalcitrant granuloma anulare. PMID- 1498406 TI - Fox-Fordyce disease: successful treatment with topical clindamycin in alcoholic propylene glycol solution. AB - We report a 66-year-old woman with a 3-year history of intensely pruritic follicular papules in the axillar, pubic and inguinal areas. Previous treatment with topical fusidic acid and gentamicin sulfate was ineffective. The clinical and histological examination was consistent with Fox-Fordyce disease. Application of clindamycin in an alcoholic propylene glycol solution led to the clearing of the lesions within 1 month. Nine months later, the treatment was stopped, and no recurrence was observed. PMID- 1498407 TI - Systemic corticosteroids do not prevent postherpetic neuralgia. AB - We review the use of corticosteroids in preventing postherpetic neuralgia (PHN) in a retrospective study over 5 years and 10 months. Out of 113 patients evaluable, 46 (40%) had PHN. 21 of these 46 patients (38%) had received prednisone (p = 0.49; n.s.). Duration and intensity of PHN were not different in the prednisone-treated group. This long-term study does not support the use of prednisone for preventing PHN. PMID- 1498408 TI - Histiocytic lymphophagocytic panniculitis (Rosai-Dorfman disease): a case report. AB - A 68-year-old woman presented with a symmetrical enlargement of the face and submandibular area associated with essential thrombocytosis. Biopsy of the lesions revealed a septal and lobular panniculitis disclosing a lymphohistiocytic and plasma cell proliferation with lymphophagocytosis by histiocytes, compatible with Rosai-Dorfman disease. The lesions regressed spontaneously without therapy over a period of 4 months. Diagnosis was confirmed by electron-microscopic examination and immunocytochemical presence of S-100 antigen within the histiocytic cells. A 2-year follow-up did not demonstrate any evidence of recurrence. PMID- 1498409 TI - Anxiety and the patient for breast biopsy. PMID- 1498410 TI - From one to another. AB - Organ transplantation is now well established as an excellent treatment for many previously fatal diseases of vital organs. For an organ to be of use to the recipient the cells must be alive but apart from kidney and hepatic lobe donation from a close blood relative, organs are removed from dead patients. The cause of death is usually a head injury or intracerebral bleed with permanent and complete destruction of the brain stem. Thus organ donation to save a life is usually associated with a tragedy for the donors and their families. PMID- 1498411 TI - A cardiac transplant programme--the nurses role. AB - In 1967 the first heart transplant was performed by Dr Christian Barnard in Capetown. Attempts to establish the technique at units worldwide produced poor results, mainly due to rejection and infection. In the 1970s, particularly at Stanford University Hospital, California, further work related to the detection and treatment of rejection allowed improvements in patient management and subsequent encouraging results in mortality and quality of life. The major breakthrough was, however, due to the introduction of cyclosporin into clinical practice in 1983. This immunosuppressive agent significantly reduced the mortality related to rejection. At the same time progress was made in several countries to establish the legal definition of brain death and to develop means of transporting donor organs over long distances. PMID- 1498412 TI - Total quality management within the NHS. AB - Total quality management is a system which enables managers to analyse and develop their services within a common framework. It incorporates the needs and preferences of service users in the setting and improvement of quality standards, within resource constraints. PMID- 1498413 TI - Extra-oral interosseous integration and it's application. PMID- 1498414 TI - The Claude S. Hudson Award of the American Chemical Society for 1992. PMID- 1498415 TI - Epiglycanin--a carcinoma-specific mucin-type glycoprotein of the mouse TA3 tumour. PMID- 1498416 TI - Oligosaccharins--oligosaccharides that regulate growth, development and defence responses in plants. PMID- 1498417 TI - Amino-sugar glycosidase inhibitors: versatile tools for glycobiologists. PMID- 1498418 TI - Denervation-induced changes in lectin binding to sarcolemmal glycoproteins: exposure of cryptic recognition sites. AB - The increase in Concanavalin A (ConA) binding to sarcolemmal membranes of rat skeletal muscle following denervation has been attributed to conformational changes in membrane glycoproteins resulting in the unmasking of previously cryptic ConA binding sites (Leung et al., 1982). In this study, analysis of lectin binding patterns to alpha-fucosidase- or sialidase-treated sarcolemmal membranes reveals that the fucose moieties of carbohydrate structures may be principally involved in the unmasking process. By contrast, sialic acid has no apparent effect on the availability of the number of ConA binding sites, but plays a significant role in the masking of other lectin recognition sites. PMID- 1498419 TI - Development and characterization of monoclonal antibodies against a mucin-type glycoprotein. AB - The preparation of greater than 30 different hybridomas, all secreting IgM class antibodies against epiglycanin, a glycoprotein at the surface of the mouse mammary carcinoma cell line TA3-Ha, is described. The specificities of 10 of the antibodies, with affinity constants in the range of 10(8)-10(10) l/mol were compared in an enzyme competitive binding assay. The affinity of epiglycanin was strongly reduced for all antibodies tested by incubation with periodate (10 mM, 4 degrees C) and was reduced for most of the antibodies by endo-alpha-N-acetyl- D galactosaminidase. This suggested that carbohydrate, and specifically the Gal beta (1----3)GalNAc disaccharide, formed an integral part of the epitopes of most of the antibodies. The isolated disaccharide, however, exhibited 250,000 times less inhibitory activity in the competitive binding assay than epiglycanin. The binding capacity of epiglycanin was also reduced by incubation with trypsin or pronase, suggesting a high molecular weight dependency for binding. Incubation with sialidase increased its affinity for the antibodies. The binding of the antibodies to epiglycanin was strongly inhibited by peanut agglutinin, and to a lesser extent by lectins from Triticum vulgaris, Ricinus communis, Pisum sativum and Phaseolus vulgaris. None of the antibodies bound to any of eight different gangliosides immobilized on HPTLC plates. Mono- (Fab) and divalent [F(ab')2] fragments of the antibodies possessed very low affinity for epiglycanin. The results demonstrated that the specificities of the antibodies are related, but distinguishable, and they suggest that this epiglycanin-IgM model may be useful for studies on the general principles of the interaction between IgM antibodies and mucin-type glycoproteins. PMID- 1498420 TI - Subunit-specific sulphation of oligosaccharides relating to charge-heterogeneity in porcine lutrophin isoforms. AB - Lutrophin (LH) consists of an array of isoforms with different charges and bioactivities. This study was undertaken to clarify specifically how oligosaccharides of alpha and beta subunits contribute to LH isoform charges. Porcine LH (pLH) was separated into four isoforms by isoelectric focusing (IEF), followed by subunit isolation. Their oligosaccharides were released by hydrazinolysis, labelled by reduction with NaB3H4, and fractionated by HPLC with a Mono Q column into five populations differing in the number of sulphate (S) and sialic acid (N) residues, designated as Neutral, N-1, S-1, S-N and S-2. Oligosaccharides were predominantly sulphated (S-1 and S-2) and infrequently sialylated (N-1 and S-N). Further analysis, including concanavalin A (Con A) affinity chromatography, desialylation, desulphation, sequential exoglycosidase digestion and methylation, clarified the structures of the acidic oligosaccharides. All were of the biantennary complex type. Their two peripheral branches were SO4-4GalNAc beta 1-4Glc-NAc and GalNAc beta 1-4GlcNAc or GlcNAc in S-1, SO4-4GalNAc beta 1-4GlcNAc and Sia alpha 2-6Gal beta 1-4GlcNAc in S-N, and (SO4-4GalNAc beta 1-4GlcNAc)2 in S-2 (where GalNAc is N-acetylgalactosamine and GlcNAc is N-acetylglucosamine). Ten percent of S-1 and of S-N had a bisecting GlcNAc residue. Sulphate residues occurred in nearly the same amount for both subunits; however, the alpha and beta subunits were sulphated differently. S-1 predominated in the alpha subunit, while S-1 and S-2 were major components in the beta subunit.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1498421 TI - Structural analysis of the N-linked glycan chains from a stylar glycoprotein associated with expression of self-incompatibility in Nicotiana alata. AB - Self-incompatibility in flowering plants of the family Solanaceae is mediated by the product of the S-allele. The allelic products of the S-gene in the female sexual tissues of the pistil are glycoproteins in the mol. wt range 28-32 kDa. These S-glycoproteins have been isolated from styles of Nicotiana alata, homozygous for the S1- and S2-alleles. Earlier studies have indicated that the single potential N-glycosylation site on the S1-glycoprotein bears a glycan chain, whereas of the four potential N-glycosylation sites on the S2 glycoprotein, three are glycosylated. This paper describes the purification and characterization of the N-linked glycan chains from these two glycoproteins. Oligosaccharides were cleaved off the glycoproteins using peptide-N4-(N-acetyl beta-glucosaminyl)asparagine amidase F (N-glycanase F) and separated by anion exchange HPLC. Four types of hybrid structure were defined by chemical techniques, fast atom bombardment-mass spectrometry (FAB-MS) and 1H-NMR. Although the relative amounts differed, all four structures were found on both the S1- and S2-glycoproteins, and are heterogeneous at some N-glycosylation sites. No O linked glycans were detected on the S2-glycoprotein. These results are discussed in relation to the potential of the structural diversity residing in this array of glycoforms to play a role in allelic specificity. PMID- 1498422 TI - Synthesis of a photoreactive, radiolabelled derivative of the oligosaccharide of GM1 ganglioside. AB - A photoreactive, radioiodinatable derivative of the oligosaccharide (GM1OS) of ganglioside GM1 was synthesized as follows: GM1OS was generated from GM1 by ozonolysis and alkaline fragmentation, and reductively aminated to GM1OSNH2 (1 amino-1-deoxymonosialogangliotetraitol). The latter compound was then reacted with N-hydroxysuccinimidyl-4-azidosalicylic acid (NHS-ASA) to form GM1OSNH-ASA [1 (4-azidosalicoylamido)-1-deoxymonosialogangliotetraitol], which was radioiodinated and further purified. To test the [125I]GM1OSNH-IASA [1-(4 iodoazidosalicoylamido)-1-deoxymonosialogangliotetraitol+ ++] as a probe for ganglioside-binding proteins, the derivative was incubated with cholera toxin, which specifically binds GM1, followed by photolysis and sodium dodecyl sulphate polyacrylamide gel electrophoresis. The probe only labelled the B or binding subunit of cholera toxin, but not the A or adenylyl cyclase activating subunit. Labelling was inhibited by excess GM1OS, but not by the oligosaccharides from gangliosides GD1a and GD1b. [125I]GM1OSNH-IASA and analogous oligosaccharide derivatives may be valuable probes for detecting ganglioside-binding proteins. PMID- 1498423 TI - Analysis of kidney mRNAs expressed from the rat beta-galactoside alpha 2,6 sialyltransferase gene. AB - beta-Galactoside alpha 2,6-sialyltransferase (SiaT-1), like other glycosyltransferases, is differentially expressed in rat tissues. Two distinct size classes of SiaT-1 mRNAs expressed in rat kidney are comprised of at least three SiaT-1 transcripts. One mRNA, RKE, represents the larger transcript class (4.7 kb) and predicts a polypeptide identical to the hepatic SiaT-1. In transfected Chinese hamster ovary (CHO) cells, RKE polypeptides exhibit hemi perinuclear staining with a SiaT-1 antibody (Ab-267) that is consistent with Golgi localization. RKE transfectants display cell-surface alpha 2,6-sialic acid linkages as determined by lectin affinity staining. Two other mRNAs, RKA and RKB, are members of a smaller size class (3.6 kb) that comprise predominant SiaT-1 transcripts in rat kidney. Both RKA and RKB encode polypeptides that are missing the amino-terminal 232 residues, but retain 171 amino acids of RKE carboxy terminal sequence information. A short, leucine-rich peptide present in the divergent amino-terminus of RKA has sequence similarity to the secretory signal domain of several eukaryotic secretory and cell-surface proteins. In transfected CHO cells, both RKA and RKB polypeptides display an immunostaining pattern that is distinct from that of the Golgi-associated SiaT-1 protein (RKE). Furthermore, RKA or RKB transfectants do not display alpha 2,6-sialic acid linkages on cell surface glycoconjugates. Consistent with the expression of divergent SiaT-1 mRNAs in rat kidney, protein blot analysis of rat tissue homogenates with Ab-267 reveals that in addition to protein that co-migrates with hepatic SiaT-1, rat kidney expresses a unique size class of SiaT-1 proteins. PMID- 1498424 TI - Mouse DNA clones and probes. PMID- 1498425 TI - Mouse chromosome 1. PMID- 1498427 TI - Mouse chromosome 8. PMID- 1498426 TI - Mouse chromosome 7. PMID- 1498428 TI - Mouse chromosome 9. PMID- 1498429 TI - Mouse chromosome 10. PMID- 1498430 TI - Mouse chromosome 11. PMID- 1498432 TI - Mouse chromosome 13. PMID- 1498431 TI - Mouse chromosome 12. PMID- 1498433 TI - Mouse chromosome 2. PMID- 1498435 TI - Mouse chromosome 15. PMID- 1498436 TI - Mouse chromosome 16. PMID- 1498434 TI - Mouse chromosome 14. PMID- 1498439 TI - Mouse chromosome 19. PMID- 1498438 TI - Mouse chromosome 18. PMID- 1498440 TI - Mouse X chromosome. PMID- 1498437 TI - Mouse chromosome 17. PMID- 1498441 TI - Mouse Y chromosome. PMID- 1498442 TI - Mouse chromosome 3. PMID- 1498443 TI - Mouse chromosome 4. PMID- 1498444 TI - Mouse chromosome 5. PMID- 1498446 TI - Model of the dynamics of receptor potential in a mechanoreceptor. AB - Mechanoreceptors are physiological units that convert mechanical stimuli to neural responses. An important one in the skin is the Pacinian corpuscle, which consists of a nerve ending surrounded by a capsule that is made up of alternating layers of fluid and elastic shells. In this paper a capsule model is coupled to a model for the dendrite via a variable representing the hoop strain imposed by the capsule on the receptor membrane of the dendrite. The transient behavior of the receptor potential due to step and periodic displacement-type stimuli imposed on the outer membrane of the capsule is investigated, and the results are compared to those of analogous experiments. The model is used to develop hypotheses concerning the role of the capsule as a filter for mechanical stimuli. PMID- 1498447 TI - Computer modeling of pole formation in cell division. AB - The regular position of spindle poles in bi- and multipolar cell divisions is interpreted as the result of expanding caps on the surface of cell nuclei first proposed by Mazia in 1986. In a computer model it is shown that expanding caps position their centers with the maximal distance between them, which is in complete accordance with findings in experimentally influenced cell divisions in which multiple poles are formed. PMID- 1498449 TI - A method for the analysis of biological transduction phenomena. AB - Biological transduction can be defined as the triggering of a cellular response by the binding of molecules of effector substances to specific cellular sites. An example of biological transduction, analyzed in this report, is the triggering of T-cell proliferation by the binding of T-cell growth factor (TCGF) to specific TCGF-binding sites on responsive T-cells. Sigmoidal or S-shaped curves often result when measurements of biological response are plotted as a function of concentration of effector substance. Such curves suggest that effector molecules must bind a critical number of cellular sites, and this critical number of bound complexes must undergo secondary events (cross-linking, association, internalization, second messenger release, etc.) in order to initiate the biological response. The method described here estimates the critical number of cellular sites (R) and the probability of these secondary events (PS/B) as follows: (1) The total number of cellular sites (N) is estimated from binding data, and the probabilities (PB) of effector molecules binding to a site are estimated from response data. (2) The response data are assumed to follow the summed binomial distribution function, which is equated to the incomplete beta function. (3) R and PS/B are estimated by applying nonlinear regression to the incomplete beta function. The T-cell data to which the method was applied gave N = 15,000, R = 5, and PS/B = 7.22 x 10(-4). These results show that the binding of very few TCGF molecules is required for activation of T-cells and that the probability of the secondary events leading to cell proliferation is much smaller than the probability of TCGF binding to T-cells. The method described can be used to analyze any biological transduction experiments where both binding and biological response data are available. PMID- 1498448 TI - Estimation of parity progression ratios from the truncated distribution of closed and open birth intervals. AB - A procedure to estimate parity progression ratios in a population from the truncated distribution of open and closed birth intervals is presented. The approach is quite simple in computation and data needs. It does not require any separate data on age at last birth to the women of completed fertility as in earlier methods. The procedure is illustrated with an observed set of data. PMID- 1498445 TI - Mouse chromosome 6. PMID- 1498450 TI - Optimal control of tumor size used to maximize survival time when cells are resistant to chemotherapy. AB - The high failure rates encountered in the chemotherapy of some cancers suggest that drug resistance is a common phenomenon. In the current study, the tumor burden during therapy is used to slow the growth of the drug-resistant cells, thereby maximizing the survival time of the host. Three types of tumor growth model are investigated--Gompertz, logistic, and exponential. For each model, feedback controls are constructed that specify the optimal tumor mass as a function of the size of the resistant subpopulation. For exponential and logistic tumor growth, the tumor burden during therapy is shown to have little impact upon survival time. When the tumor is in Gompertz growth, therapies maintaining a large tumor burden double and sometimes triple the survival time under aggressive therapies. Aggressive therapies aim for a rapid reduction in the sensitive cell subpopulation. These conclusions are not dependent upon the values of the model constants that determine the mass of resistant cells. Since treatments maintaining a high tumor burden are optimal for Gompertz tumor growth and close to optimal for exponential and logistic tumor growth, it may no longer be necessary to know the growth characteristics of a tumor to schedule anticancer drugs. PMID- 1498451 TI - Low-intensity combination chemotherapy maximizes host survival time for tumors containing drug-resistant cells. AB - Recent clinical trials have shown that for some cancers, high-intensity alternating chemotherapy does not significantly improve either survival times or response rates compared with nonalternating therapy. The current study uses optimal control to determine the best way to treat a tumor that contains drug resistant cells that cannot be destroyed. The delivery of two non-cross-resistant chemotherapeutic agents is limited by bounds on the drug concentration and the dose intensity. This ensures that the drug toxicity stays within a tolerable range. The aim of the therapy is to maximize the host survival time, defined as the time over which the tumor burden can be kept below a fixed bound. The model is posed as a free terminal time, optimal parameter selection problem in which the constraints are continuously parametrized by time and the number of courses of therapy is free to vary. New theory is developed so that the optimal parameter selection problem can be solved as a sequence of fixed terminal time problems using existing optimal control software. Numerical simulations of Gompertz tumor growth showed that a treatment maintaining a high tumor burden doubled and sometimes tripled with survival time under aggressive therapy. When these simulations were repeated using exponential and logistic tumor growth models, the tumor burden during treatment had little influence upon survival time. In all simulations, survival time was not extended by delivering the anticancer drugs concurrently instead of staggering the treatment arms. PMID- 1498452 TI - Maximum sustainable yield of populations with continuous age-structure. AB - We address the problem of finding the harvesting policy that will maximize the yield and maintain a population in a steady state. The population is characterized by continuous age classes and therefore follows differential equations. Here, we assume that the equations are linear (no density dependence). Two possible constraints are considered: either recruitment or total population are fixed to a constant. Under these conditions, the optimal policy is to harvest the fraction theta of a younger age class a and to harvest totally an older age class b. The optimal solution (theta, a, b) can be calculated explicitly if the fecundity and mortality schedules are given. The solution is compared to the simpler strategy of harvesting all individuals beyond a single age class a. It is shown that the latter strategy can be much less profitable than harvesting two age classes because it cannot take account of the different values of individuals according to their age. PMID- 1498453 TI - Enteral nutrition: accessing patients. AB - This review highlights important points in regard to use of the enteral route to provide nutrition support to nutritionally compromised patients. Enteral nutrition has become technologically advanced medical therapy in the last 15 yr, and as clinical nutrition continues to develop, further advances will be made. With the range of access routes and delivery systems available, appropriate nutrition can be provided in a safe, effective manner. PMID- 1498454 TI - Catabolic response and parenteral nutrition after simultaneous kidney-pancreas transplantation. AB - The aim of the study was to quantify the catabolism rate induced by simultaneous kidney-pancreas transplantation and to evaluate the impact of parenteral nutrition (PN) on recovery of graft function. Twenty-six diabetic uremic patients were studied. The average urea nitrogen production (UNP) was 5.2 +/- 1.7 g during the first 24 h after transplantation, while patients did not receive energy and nitrogen support. Energy (30 kcal.kg-1.day-1) and nitrogen (0.15 g.kg-1.day-1) intake started 24 h after surgery. In 14 patients, a mixed regimen was adopted (70% carbohydrates, 30% lipids), and 12 patients received only hypertonic glycidic solutions. The recovery of kidney function was immediate in all cases, with a prompt decrease in blood urea nitrogen and serum creatinine levels. C peptide levels rose immediately after the revascularization of the pancreas graft and remained within the normal range during the PN period. No significant difference was observed in UNP or glucose tolerance between the mixed-regimen and glycidic groups. However, on average 6.6, and 1.5 hyperglycemic episodes occurred during the 1st wk of PN in the glycidic and mixed-regimen groups, respectively. The posttransplantation catabolism rate was similar to that induced by an elective major surgical procedure. Eucaloric PN did not affect the recovery of kidney and pancreas graft function. A mixed energy regimen seems to be most suitable for kidney-pancreas transplant patients because it prevents hyperglycemia which might be misdiagnosed as rejection. PMID- 1498455 TI - Variations in plasma amino acids in septic patients subjected to parenteral nutrition with a high proportion of branched-chain amino acids. AB - Sepsis is characterized by an increase in the plasma concentration of aromatic amino acids (AAAs) and those containing sulfur and a decrease in the branched chain amino acids (BCAAs). We studied changes in the plasma aminogram of septic patients given different types of total parenteral nutrition (TPN), analyzing variations in accordance with the type of TPN used and the importance that the use of BCAA may have in these patients. We studied 80 patients with peritonitis divided into two groups of 40 patients each: group 1 was given a solution with 22.5% BCAA and group 2 a solution with 45% BCAA. High BCAA content caused an increase in the plasma concentrations of these amino acids and in the BCAA/AAA quotient and a decrease in AAAs. Plasma concentrations of leucine and valine reached high, potentially toxic levels at 15 days when solutions with high BCAA content were used. Glycine increased in group 1, which may be important because of its tendency to produce hyperammonemia. BCAAs are of unquestioned nutritional importance in view of the evidence of changes that take place in muscle protein catabolism and in plasma amino acids. In the phase of increased protein catabolism, we saw a plasma amino acid pattern in keeping with the existing metabolic situation. The need for BCAA diminishes when the hypercatabolic state disappears. PMID- 1498456 TI - Glucose metabolism in advanced lung cancer patients. AB - Although it is generally accepted that altered nutrient intake and metabolism are responsible for the progressive loss of body weight observed in most advanced cancer patients, there is still considerable controversy regarding the contributory role of changes in both resting energy expenditure (REE) and glucose metabolism. Several studies suggest increases in both REE and glucose appearance in advanced cancer patients compared with healthy control subjects, whereas others revealed no changes in either metabolic parameter. We measured REE with indirect calorimetry and glucose kinetics with a primed constant infusion of D-[U 14C]glucose and D-[6-3H]glucose over the last 4 h of a 24-h fast in 32 advanced lung cancer patients immediately after diagnosis and before any chemotherapy or radiotherapy and in 19 healthy volunteer subjects. REE for the lung cancer group was not significantly different from that in the control group (1535.8 +/- 78.0 vs. 1670.2 +/- 53.9 kcal/day, respectively, p = 0.151). When REE was expressed as a function of body weight, or lean body mass, no differences between the two groups were observed. The rate of glucose appearance was 9.88 +/- 0.36 mumol.kg 1.min-1 in the cancer patients and 10.15 +/- 0.53 mumol.kg-1.min-1 in control subjects (p = 0.667), of which 50.4 versus 58.2%, respectively, was oxidized. The amount of glucose recycled was 13.54 +/- 1.22% in cancer patients and 15.08 +/- 0.99% in control subjects (p = 0.394). The amount of VCO2 from direct oxidation of glucose was 23.39 +/- 0.74% in cancer patients and 27.45 +/- 1.36% in control subjects (p = 0.006).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1498458 TI - Total dietary restriction and thymus, spleen, and phenotype and function of splenocytes in growing mice. AB - To study the immunological effect of total dietary restriction, BALB/c mice were limited to reduced body growth or maintained at practically constant body weight between 21 and 61 days of age by giving them 70% (R70%) or 55% (R55%) of the average daily food intake of the control group fed ad libitum. Thymus and spleen weight were decreased, but thymus size was maintained in proportion to body weight in R70% mice, whereas the ratio of thymus weight to body weight was significantly decreased in R55% mice. In restricted mice, splenocytes showed a lower percentage of B lymphocytes and a higher percentage of T lymphocytes. Results of stimulation showed that proliferation capacity was increased for B lymphocytes and decreased for T lymphocytes in restricted mice. Our data show the importance of studying the thymus over a period, because normal thymus growth was first greatly impaired by dietary restriction, and subsequent thymus involution was delayed, showing that an isolated comparison between the thymus of growing mice is not enough. Our data show the interest of determining the percentage of lymphocyte populations parallel to their response to mitogen stimulation. PMID- 1498457 TI - Effects of graded levels of high-molecular-weight carrageenan on colonic mucosal thymidine kinase activity. AB - Graded levels of high-molecular-weight carrageenan were fed to male Fischer 344 rats to investigate the effects of carrageenan on colonic cell proliferation. Four groups of 7 rats consumed diets containing 0 (control), 0.65, 1.31, or 2.61% carrageenan ad libitum for 4 wk. These levels were designed to simulate (on a milligram-per-kilogram basis) 25, 50, and 100 times the maximal human carrageenan intake. After an overnight fast, the rats were anesthetized, and the colonic mucosa was removed and homogenized. A supernatant was prepared and assayed for total protein and thymidine kinase activity (a marker for cell proliferation). Increasing levels of carrageenan resulted in stepwise increases in total mucosal protein and in thymidine kinase specific (units per milligram of protein) and total (units per centimeter of colon) activity. However, increases in thymidine kinase activity were statistically significant only at the highest dose of carrageenan. No histological abnormalities were associated with any level of carrageenan feeding. These results suggest a clear dose-response increase in colonic mucosal cell proliferation with increasing doses of carrageenan; however, the effect at doses approximating 19 times maximal human intake was not statistically different from that for control rats under the conditions of this study. PMID- 1498460 TI - Total parenteral nutrition in surgical illness: how much? How good? AB - Using primed constant infusions of isotopes and indirect calorimetry, we assessed protein, glucose, and fat kinetics in severely ill surgical patients suffering from sepsis, major trauma, gastrointestinal cancer, or nutritional depletion from benign disease. We also assessed the effect of 5 days of total parenteral nutrition (TPN) on abnormal metabolism in these states. In the basal state, patients with sepsis, trauma, or cancer had an elevated rate of net protein catabolism due to an increased rate of whole-body protein catabolism, whereas whole-body protein synthesis was not impaired. TPN had no impact on the elevated rate of whole-body protein catabolism in these conditions but decreased the rate of net protein catabolism, suggesting that increased substrate availability optimizes whole-body protein synthesis. Consequently, few surgical patients became anabolic while receiving TPN. In contrast, patients with nutritional depletion from benign disease had a decreased rate of net protein loss compared with volunteers and could be made anabolic with the administration of TPN. All patients studied had an elevated rate of plasma glucose production, impaired glucose oxidation, and an increased rate of Cori cycling in the basal state. After 5 days of TPN, most surgical patients showed improved ability to oxidize glucose, but the high rates of glucose recycling to lactate persisted. Patients suffering from sepsis, trauma, or cancer had an enhanced rate of lipolysis in the basal state associated with an increased rate of whole body-fat oxidation compared with healthy volunteers. After administration of TPN, whole-body fat oxidation was significantly decreased in patients with trauma but increased in patients with sepsis or cancer.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1498459 TI - Nutrition support in a patient with alpha 1-antitrypsin deficiency. PMID- 1498461 TI - Measuring variability. PMID- 1498462 TI - The physical basis of precocity and dullness. 1893. PMID- 1498464 TI - Monoclonal antibodies to red cell alloantigens with particular reference to anti D. PMID- 1498463 TI - The Miltenberger subsystem: is it obsolescent? PMID- 1498465 TI - Naturally occurring anti-band 3 antibodies. PMID- 1498466 TI - The role of UV radiation in the prevention of human leukocyte antigen alloimmunization. PMID- 1498467 TI - Penta RISc soil--a rapid, on-site screening test for pentachlorophenol in soil. PMID- 1498468 TI - Evaluation of an immunoassay kit for the detection of certain organochlorine (cyclodiene) pesticide residues in apple, tomato, and lettuce. PMID- 1498469 TI - Enzyme-linked immunosorbant assay (ELISA) of simazine for Delhi and Yolo soils in California. PMID- 1498470 TI - Resazurin reduction tests as an estimate of coliform and heterotrophic bacterial numbers in environmental samples. PMID- 1498472 TI - Photochemical behavior of organic phosphate esters in aqueous solutions irradiated with a mercury lamp. PMID- 1498471 TI - New rapid method to evaluate the median effect concentrations of xenobiotics in hydrobionts. PMID- 1498473 TI - Seasonal fluctuations of organochlorine compounds in the water of the Strimon River (n. Greece). PMID- 1498474 TI - Trihalomethanes and halogenated organic formation in water treatment plant. PMID- 1498475 TI - Determination of lead in paired samples of human blood and synovial fluid. PMID- 1498476 TI - In vitro effect of glutathione on mitomycin-C in human lymphocytes. PMID- 1498477 TI - Differential responses of regional brain polyamines following in utero exposure to synthetic pyrethroid insecticides: a preliminary report. PMID- 1498478 TI - Effects of oximes and atropine on acute phosphamidon intoxication in Bubalus bubalis. PMID- 1498479 TI - Effect of glyphosate and nitrapyrin on selected bacterial populations in continuous-flow culture. PMID- 1498480 TI - Acute toxicity of the mosquito larvicide, Bacillus sphaericus, to the grass shrimp, Palaemonetes pugio, and mummichog, Fundulus heteroclitus. PMID- 1498481 TI - Effect of malathion on the brain acetylcholinesterase activity of bluegill sunfish Lepomis macrochirus. PMID- 1498482 TI - Cadmium sensitivity inducing structural responses in Salvinia molesta Mitchell. PMID- 1498483 TI - Influence of temperature and nutrient strength on the susceptibility of Saccharomyces cerevisiae to heavy metals. PMID- 1498484 TI - Embryotoxic action of methyl mercury on coho salmon embryos. PMID- 1498485 TI - Partitioning of PCBs in the muscle and reproductive tissues of paddlefish, Polyodon spathula, at the Falls of the Ohio River. PMID- 1498486 TI - Total arsenic in water, fish, and sediments from Lake Xolotlan, Managua, Nicaragua. PMID- 1498487 TI - Purple spotted gudgeon: its use as a standard toxicity test animal in tropical northern Australia. PMID- 1498488 TI - The relationship of estrogen receptor status to DNA ploidy in breast cancer. AB - The relationship of estrogen receptor (ER) status to DNA ploidy was investigated in 121 patients with breast cancer who underwent surgery. Lymph node status was evaluated histologically and ER levels were determined by the dextran-coated charcoal method, with a level of 3 fmol/mg.protein being considered positive. Flow cytometric DNA content was analyzed using paraffin-embedded tissue blocks. Sixty-three percent of the specimens were ER+, while 37 percent were negative. Sixty-one patients (50.4 percent) were diploid and 60 aneuploid. A statistically significant correlation between the ER positivity rate and diploid DNA was found. Higher ER levels were seen in the postmenopausal patients with diploid tumors than in those with aneuploid tumors and there was a significant tendency for ER levels to be higher in the diploid tumors. Nodal status was not correlated with ER positivity or ploidy pattern. The present results indicate that ER levels are correlated with DNA ploidy, and reflect the degree of functional differentiation. PMID- 1498489 TI - Postoperative pyothorax. AB - Twenty-five cases of pyothorax occurred in a series of 1281 thoracotomies. Almost all cases of pyothorax without bronchopleural fistula were successfully treated by closed drainage and irrigation alone. On the other hand, patients with pyothorax and fistula who were treated only with closed drainage almost all had a poor outcome. When pyothorax with fistula was treated by closed drainage and irrigation followed by further procedures such as open window thoracostomy, muscle plombage and/or omentopexy, treatment was successful. It is concluded that pyothorax without fistula may be cured by closed drainage and irrigation alone, but that pyothorax with fistula requires operative intervention such as open window thoracostomy or omental flap as soon as possible. PMID- 1498490 TI - Radical mastectomy with parasternal node dissection or radiation to the parasternal region for breast cancer of medial or central location. AB - In order to establish a therapeutic approach for primary breast cancer of medial and central origin, we reviewed 183 patients who had been treated by one of the following three modalities at the Second Department of Surgery, Osaka University Medical School between January, 1965 and December, 1980. Group A (n = 70): standard radical mastectomy alone; Group B (n = 34): standard radical mastectomy followed by postoperative irradiation to the parasternal and supraclavicular regions, and; Group C (n = 62): extended radical mastectomy that included removal of the parasternal lymph nodes. The background factors of the three groups were not significantly different. The overall survival five and ten years following surgery in the three groups were 91 percent and 79 percent in group A, 82 percent and 67 percent in group B, and 82 percent and 70 percent in group C, respectively, showing no significant difference in overall survival among the three groups. When the patients were classified according to the extent of axillary lymph node involvement, there was no difference in survival among the three treatments in patients who had less than three lymph node metastases in the axilla. However, treatment of the parasternal lymph nodes improved survival in the patients who had more than four lymph node metastases in the axilla. Parasternal lymph node involvement definitely worsened the prognosis, showing it to be a good prognostic factor. Thus, extended radical mastectomy should be considered for patients with breast cancer of medial or central location, when extended axillary lymph node involvement is found. PMID- 1498491 TI - The role of the abdominal sympathetic nervous system in regulating portal venous flow and its functional distribution. AB - The role of the abdominal sympathetic nervous system in regulating portal venous flow (PVF) was examined in anesthetized rats using an ultrasonic volume flowmeter. Electrical stimulation of the hepatic sympathetic branch, given at 10 Hz, 1 ms, 10 s and 12 V, caused approximately a 28 percent reduction in PVF, which was equivalent to that produced by occlusion of the bilateral carotid arteries for 30 s, without causing any change in the systemic arterial pressure. Stimulation of the major splanchnic nerve decreased PVF, the response being greater by stimulation of the right nerve than by stimulation of the left (p less than 0.05). Bilateral adrenalectomy shortened the recovery time without changing the magnitude or lateral predominancy. Neither proper hepatic arterial occlusion nor partial hepatectomy affected the response. In the partially hepatectomized animals, stimulation of the hepatic branch did not decrease the splenic flow but decreased the superior mesenteric venous flow (SMVF) and induced a similar response in PVF even when the SMVF was interrupted. An intraportal injection of noradrenaline decreased PVF dose-dependently. These findings indicate that the sympathetic nerve regulates PVF directly, and that there is functional laterality of the regulatory mechanism in the abdominal cavity, which suggests that adrenal factors work together with the nerve that supplies the portal vein. PMID- 1498492 TI - A novel anticancer treatment for xenoplanted human gastric cancer using polyamine antimetabolites in a low polyamine diet. AB - The aim of the present study was to evaluate a new anticancer treatment for gastrointestinal cancer, using a combination of polyamine antimetabolites, an anticancer agent and a low-polyamine state. Two polyamine antimetabolites, given as either 40 mg/kg of methylglyoxal-bis-guanylhydrazone (MGBG) or ethylglyoxal bis-guanylhydrazone (EGBG) and a normal diet (ND), or 20 mg/kg of each drug and a low polyamine diet (LPD), together with 1,000 mg/kg of alphadifluoromethylornithine (DFMO) were administered ip to nude mice for six consecutive days. Mitomycin C (MMC) at 2 mg/kg was then given ip for 3 alternate days. The combination of MGBG or EGBG with DFMO plus MMC resulted in an enhanced antitumor efficacy on LPD. However, the combination which included EGBG was much more enhanced than that which included MGBG and there was no evidence of any tumor regrowth. Weight loss was minimal or nil in the mice given the combination with EGBG, but was evident in those given the combination with MGBG. These results led to the conclusion that in mice, the combined therapy of EGBG with DFMO plus MMC and LPD is a safe and effective regimen for the treatment of gastric cancer. PMID- 1498493 TI - Portal circulation and the function of hepatocytes during ex vivo perfusion of the rat liver preserved for six hours after core cooling. AB - Portal circulation and the function of hepatocytes during isolated organ perfusion were compared between the rat liver perfused immediately after extirpation and the liver perfused after core cooling and six hours of preservation. Nine rat livers were extirpated after core cooling, preserved for six hours in University of Wisconsin (UW) solution at 4 degrees C and then were connected to a perfusion chamber (hypothermic preservation group: 6-hr HP group). Six rat livers were immediately connected to the perfusion chamber after extirpation (control group). During 60 minutes of isolated liver perfusion, both portal circulation and the function of hepatocytes were determined every 10 minutes. Portal vein resistance increased and portal blood flow decreased during the first 20 minutes of perfusion and then stabilized in both groups. Portal vein resistance was significantly higher and portal blood flow was significantly lower for the first 10 minutes of perfusion in the 6-hr HP group, compared to the control group. The function of hepatocytes, determined by the rate of elimination of ammonia, oxygen consumption, and glucose availability were depressed in the 6 hr HP group, compared to the control groups during isolated liver perfusion. However, there was no statistically significant difference of portal perfusion and the function of hepatocytes between the two groups at the end of perfusion. The results of the present study indicate that the rat liver can be preserved in a satisfactory condition for six hours by the use of hypothermic preservation, coupled with core cooling. PMID- 1498494 TI - Effect of prostacycline analogue OP-41483 and perfusate on liver preservation by simple hypothermia in rats. AB - Changes in rat livers preserved by simple cooling immersion in modified Sacks' solution, Ross' solution and Ross' solution with OP-41483, a PGI2 analogue, were compared after 12, 24, 36, and 48 hours. The viability of the preserved livers was assessed by measuring the tissue ATP concentrations and quantifying morphologic changes in the mitochondria observed by transmission electron microscopy using a 4-point scale, the mitochondrial score. A general trend towards progressive mitochondrial degeneration was observed in all groups. After 12 hrs of preservation, there was no significant difference between the groups. From 24 to 48 hours, the mitochondrial scores for livers preserved with OP-41483 were significantly higher than in the two other groups. No difference among the groups in tissue ATP concentration was observed at any time. Thus, OP-41483 was considered to retard mitochondrial degeneration in liver preservation by simple hypothermic immersion and does so by a mechanism not directly related to intracellular energy stores. The possibility that OP-41483 acts by stabilizing the lysosomal membrane is discussed. PMID- 1498495 TI - Biodistribution of radiolabeled monoclonal antibody after intraperitoneal administration in nude mice with hepatic metastasis from human colon cancer. AB - The utility of the intraperitoneal (IP) administration of radiolabeled monoclonal antibody (mAb) for hepatic metastasis from human colon cancer was evaluated in congenital athymic mice. The intrasplenic injection of HT-29 LMM metastatic human colon cancer cell line reproducibly results in hepatic metastasis formation in nude mice. HT-29-15, a murine mAb of IgG1 class reactive with the HT-29 LMM cell line was labeled with iodine 125. One microgram/2 microCi of labeled HT-29-15 was injected intraperitoneally into mice with hepatic metastases, and additionally IP administration of the same dose of I-125 labeled HT-29-15 with increased volume and intravenous (IV) administration of dose quantity of HT-29-15 were performed. Blood samples were obtained at 1, 3, 5 hours, and the animals were sacrificed on days 1, 3, and 5. The percent of injected dose per gram (%ID/g) of blood after IP administration of I-125 labeled HT-29-15 reached the same level of %ID/g after IV administration by 5 hours. The transfer from the peritoneal cavity to blood was delayed by increasing the volume injected. From day 1 to day 3, there was a progressive increase for hepatic metastasis/blood ratios of I-125 labeled HT-29 15 in each group. There was no difference in the hepatic metastasis/blood ratios among the three groups. IP administration of specific mAb, therefore, provides the same level of tumor uptake in hepatic metastasis from colorectal cancer, and would be advantageous in patients with both hepatic metastasis and peritoneal implants in which radioimmunodetection and radioimmunotherapy are appropriate. PMID- 1498497 TI - A rare case of fibroadenoma in a tubular adenoma of the breast. AB - We report herein a case of a 31 year old housewife who underwent an excisional biopsy for a well-circumscribed lump in her breast. The lump contained 2 histological patterns, namely, fibroadenoma and tubular adenoma. These patterns had no transitional zone, were distinct and changed abruptly. This case was histologically diagnosed as "a fibroadenoma in tubular adenoma of the breast, benign", with no other such case ever having been reported in Japan. The histological findings of this case, convinced us that tubular adenoma is closely related to fibroadenoma. PMID- 1498496 TI - A case of linitis plastica of the rectum treated by pelvic exenteration after aggressive immunochemotherapy. AB - Multidisciplinary treatment was administered to a 32 year-old man with primary linitis plastica of the rectum, which was considered inoperable due to an extensive local spread at the first operation. Thirty KE of OK-432 was injected into the tumor per week (total 90-KE) and 5 KE of OK-432 was inoculated into the intracutaneous space per week (total 125 KE). Also methotrexete (MTX 50 mg) and 5 FU (500 mg) combined were given each week by intra-arterial infusion (total 20 courses). After this immuno-chemotherapy the CEA decreased from the pretreatment value of 12.7 ng/ml to 3.6 ng/ml and the tumor size was reduced. A total pelvic exenteration could then be performed almost curatively. As a result, this patient was able to return to the society with a better quality of life and has survived for 20 months since presentation. PMID- 1498498 TI - Modified Van Praagh's operation for interrupted aortic arch with severe subaortic stenosis in a neonate. AB - A 26 day old neonate with Type B interrupted aortic arch, a ventricular septal defect and severe subaortic stenosis underwent a successful modified Van Praagh's operation, consisting of insertion of a graft between the main pulmonary artery and descending aorta, ligation of the patent ductus arteriosus and main pulmonary artery banding distal to the graft. This palliative procedure was effective and easily performed without the aid of cardiopulmonary bypass even in this severely ill neonate with such a complex defect. PMID- 1498499 TI - Primary anorectal malignant melanoma. AB - A case of primary anorectal malignant melanoma seen in a 46 year old woman is presented herein. Her most marked symptoms were bloody stools and anal pain. Endoscopic examination indicated a tumor with ulceration but without pigmentation in the anorectal region. Histologic examination of the biopsied specimens showed spindle-shaped cells with atypia proliferating in a bandlike arrangement, as in leiomyosarcoma. An abdominoperineal resection was done and detailed histological examination of the tumor confirmed the nature of the tumor to be malignant melanoma. The postoperative immunochemotherapy consisted of Dimetyl-Triazeno Imidasole-Carboxamide (DTIC), Amino-Methyl-Pyrimidinyl-Methyl-Chlorethyl Nitrosourea-Hydrochlori de (ACNU), Vincristine (VCR) and OK-432. The patient has been well without recurrence for fifteen months following her operation through the continuous administration of these agents. PMID- 1498500 TI - Surgical management of the coronary artery to pulmonary artery fistulas; a case of a large ruptured aneurysm. AB - Three patients were treated for coronary artery-pulmonary artery fistula. Each was asymptomatic due to a coronary artery fistula. There was one instance each of myocardial infarction, mitral stenosis and a large closed ruptured aneurysm including a thrombus. All the fistulas were comprised of several small plexiform arranged vessels. The left to right shunt ratio was approximately 8 percent or less. A surgical operation was performed to close the drainage orifice of the fistulas through pulmonary arteriotomy under cardiopulmonary bypass in two patients while one patient underwent a ligation of a large abnormal vessel to the aneurysm followed by a resection of the aneurysm without cardiopulmonary bypass. A large saccular aneurysm of such fistulas is rare and a rupture of such an aneurysm is even more rare. The surgical management of coronary artery fistulas is also discussed herein. PMID- 1498501 TI - Multiple colorectal carcinomas and colorectal carcinoma associated with extracolonic malignancies. AB - In this study, we analyzed 149 surgical cases of colorectal cancer between January 1983 and August 1989. Thirteen cases (8.7 percent) of colorectal primary cancer associated with extracolonic primary malignancy of 14 lesions and 10 cases (6.7 percent) of multiple primary colorectal cancers were included. Among the 14 lesions of extracolonic primary malignancy, there were 6 gastric carcinomas, 2 endometrial carcinomas, 2 urinary bladder carcinomas, and one each in the esophagus, liver, bile duct and jejunum. The second tumor was not detected preoperatively in 3 of 4 cases of synchronous multiple primary colorectal carcinoma. A curative resection was done in 10 (77 percent) out of 13 cases of colorectal cancer associated with extracolonic malignancy, while 7 (88 percent) out of 8 cases of multiple colorectal cancers had a curative resection. Nine patients (69 percent) with colorectal cancer associated with extracolonic malignancy were disease-free for 2 months to 14 years. Seven patients (88 percent) with multiple colorectal cancers were disease-free for one to 22 years. We recommend, therefore, that in any patient with colorectal cancer, the entire large bowel should be thoroughly searched for any other primary tumors, by taking the existence of extracolonic tumors into account. A curative resection should be performed, and the follow-up period should be life-long. PMID- 1498502 TI - Immunogenicity and immunomodulatory activity of bovine surfactant (SF-RI 1). AB - Respiratory distress syndrome in preterm infants can be treated successfully by endotracheal administration of a bovine surfactant preparation (SF-RI 1). Before the routine use of xenogenic surfactant preparations can be recommended, their immunogenicity as well as their in-vivo and in-vitro immunomodulatory activity have to be investigated. High titers of anti-surfactant antibodies were detected by a sensitive ELISA after immunizing rats, rabbits and mice with SF-RI 1. Repeated endotracheal administration of SF-RI 1 resulted in a humoral antibody response in three out of eight rabbits. After treatment of 34 preterm infants with SF-RI 1 (50-200 mg/kg), a humoral immune response to SF-RI 1 could not be detected. In-vitro restimulation of peripheral blood lymphocytes with SF-RI 1 after primary in-vivo administration did not result in cell proliferation as measured by 3H-thymidine incorporation. SF-RI 1 did not stimulate peripheral blood lymphocytes of neonates in vitro. The mitogenic response of these cells to stimulation with PHA, ConA or PWM was heavily impaired in the presence of SF-RI 1 concentrations increasing from 0.04 to 4 mg/ml. These data indicate that SF-RI 1 is immunogenic and that it may have an influence on lymphocyte proliferation in vivo. PMID- 1498503 TI - Changes in cerebral oxygenation and cerebral blood volume during endotracheal suctioning in ventilated neonates. AB - The effect of endotracheal suctioning on cerebral haemodynamics was investigated in 29 newborn infants with a mean gestational age of 31 weeks (range 25-40 weeks). Prior to one of two suctioning procedures, the inspiratory fraction of oxygen was increased by 10%. Brain oxygenation and total haemoglobin concentration were estimated continuously by near infrared spectroscopy. Mean arterial blood pressure, arterial blood oxygen saturation and carbon dioxide tension were recorded simultaneously. Brain oxygenation decreased in parallel with arterial oxygen saturation during suctioning. Preoxygenation ameliorated the decrease in brain oxygenation and arterial oxygen saturation whereas there was no benefit with regard to the changes in total haemoglobin concentration, carbon dioxide tension or mean arterial pressure. Changes in total haemoglobin concentration were related closely to concomitant changes in carbon dioxide tension (p less than 0.0001) but unrelated to changes in mean arterial pressure or arterial oxygen saturation. Our findings suggest that cerebral blood volume may react to changes in carbon dioxide tension during endotracheal suctioning in mechanically ventilated neonates. Apparently, preoxygenation prior to suctioning does not ameliorate the stress in normoxic infants. PMID- 1498504 TI - Low incidence rates by birth of symptomatic coeliac disease in a Danish population of children. AB - Using the original diagnostic criteria of the European Society for Paediatric Gastroenterology and Nutrition for symptomatic coeliac disease in children, we found an average incidence rate by birth of 0.10 per 1000 live births in a demographically homogeneous Danish population over a 15-year period. This incidence rate by birth is the lowest described in an epidemiological study in contrast with rates of 0.33 to 8 per 1000 live births found in other western countries. This difference may be explained by the different diagnostic criteria used for coeliac disease. Another contributing factor may be a late and gradual introduction of gluten-containing cereals into the diet of Danish infants. PMID- 1498505 TI - Comparison of fiberendoscopy and Watson capsule for small intestinal biopsy in infants and children. AB - We analyzed the results of 607 small bowel biopsies performed over a seven-year period: 284 biopsies were obtained using a fiberendoscope and 323 biopsies using a Watson capsule. Three to six specimens were removed during endoscopy. The biopsy fragments obtained with the fiberendoscope were deeper than those obtained with the Watson capsule (p less than 0.0001) and were more often located in the duodenum (p less than 0.0001). The failure rate of the fiberendoscope biopsies (1%) was lower than for the Watson capsule biopsies (9%) (p less than 0.0001). Multiple biopsies increased the diagnostic value of fiberendoscopy which was 95% versus 85% for Watson capsule. The mean duration of the endoscopic procedure recorded in 30 children was 6.5 min for four to six samples, i.e. 1.5 min per biopsy specimen. Fiberendoscopy appears to be an efficient and safe method for performing small bowel biopsies in infants and children. PMID- 1498507 TI - Intrauterine growth in children with cerebral palsy. AB - The risk of cerebral palsy in connection with intrauterine growth retardation has been analysed in a case-control study. The case series comprised 519 children with cerebral palsy born in 1967-1982 in the west health-care region of Sweden and the control series 445 children born during the same years in the same region. The risk of cerebral palsy in small-for-gestational-age infants was significantly increased in term and moderately preterm infants. The highest proportion among infants with cerebral palsy born at term was found in tetraplegia, followed by diplegia and dyskinetic cerebral palsy. It was concluded that small for gestational age on the one hand reflects early prenatal brain damage, and on the other mediates prenatal risk factors compatible with foetal deprivation of supply and also potentiates adverse effects of birth asphyxia and neonatal hypoxia. PMID- 1498506 TI - Normokalaemic pseudohypoaldosteronism is present in children with acute pyelonephritis. AB - The present study demonstrates that renal tubular unresponsiveness to aldosterone, without associated hyperkalaemia, is present in children with acute pyelonephritis. We studied 32 children with a diagnosis of acute pyelonephritis established by high fever, flank pain/tenderness, increased blood levels of C reactive protein and significant Escherichia coli growth in the urine culture. Renal tubular function tests and determinations of plasma renin activity and aldosterone concentration were performed at diagnosis (study 1), after three days of iv gentamycin (study 2) and after 21 days of antibiotic therapy (study 3). Findings were compared to those present in 32 normal children of similar age. Despite normal plasma potassium concentration, fractional potassium excretion and transtubular potassium concentration gradient were significantly decreased in studies 1 and 2, becoming normal in study 3. Decreased renal potassium excretion coexisted with increased values for plasma renin activity and aldosterone concentration. In study 3 these hormones remained elevated only in patients with scarred kidneys. The functional alteration present in acute pyelonephritis may be directly caused by the interstitial inflammation or be mediated by some E. coli endotoxin. PMID- 1498508 TI - Danish primary schoolteachers' knowledge about asthma: results of a questionnaire. AB - We present an anonymous questionnaire inquiry involving 334 primary schoolteachers in the Randers area with the purpose of elucidating teachers' knowledge about asthma. To a series of statements about asthma, the teachers answered yes, no or don't know. A limited knowledge of different aspects of asthma in children was found, although 57% had asthma children in their classes. Specially limited was knowledge about medical treatment. Five percent had received proper instruction about asthma and had a significantly better knowledge of medical treatment (p less than 0.001-0.05). Only 57% knew that wheezing after physical exertion is a strong indicator of asthma and only 33% knew that exertion in cold weather increases the risk of an attack. It is recommended that instruction in children's diseases, especially asthma, is introduced in teacher training colleges. PMID- 1498509 TI - Growing up in Uppsala. The role of public services in identification and treatment of health and adjustment problems. Part I. Definition and classification of dependent variables. AB - A comprehensive prospective longitudinal study of health, development and social adjustment from the age of four to 18 years has been carried out in Uppsala, Sweden. This report presents the accumulated psychosocial burden up to 18 years of age for all 1715 children born in 1965 and resident in Uppsala from age 10 to 18 years. The psychosocial burden up to 18 years of age was assessed through analysis of records and register information from school health services, authorities for care of the handicapped, the Department of Child Psychiatry, social agencies and legal authorities. The analysis showed that 11.8% of the adolescents had a severe psychosocial burden up to the age of 18 years which could hamper their future life as adults. It was possible to categorize the whole birth cohort into one subgroup without manifest psychosocial problems and five different subgroups with serious problems: the six groups (severe mental or physical handicap, antisocial behaviour, psychiatric problems, social support, multiple problems, "normal") had specific profiles concerning sex distribution, symptoms, social background, utilization of care services and delinquency. PMID- 1498510 TI - Growing up in Uppsala. Part II. Could adolescents with severe psychosocial problems have been identified by symptoms observed in school at age 10 years? AB - The study comprised all 1715 children born in 1965 and resident in Uppsala at age 10 and 18 years. Data were collected through teacher interviews and analysis of school health records in grade 3 at the age of 10 years. The psychosocial burden up to the age of 18 years was assessed on the basis of all registered contacts with official institutions outside school (authorities for care of the handicapped, Department of Child Psychiatry, social agencies, legal authorities). Approximately 12% of the adolescents were clearly in a situation of manifest psychosocial risk on the threshold of adult life. These adolescents were assigned to five mutually exclusive problem groups comprising different sex distribution, symptoms and utilization of institutional care. The analysis of the relationship between data from grade 3 and the psychosocial burden up to 18 years of age showed that the information available to the school did not permit reasonably secure predictions of the child's psychosocial situation at the end of adolescence. Observations in school of pre-adolescent children cannot be used as a basis for risk-group strategies aiming at concentrating early treatment measures and resources to a restricted number of children at risk. However, the prognosis is apparently serious for a limited number of 10-year-olds with serious problems in school. PMID- 1498511 TI - Greek immigrant children in southern Sweden in comparison with Greek and Swedish children. III. Energy and nutrient intake. AB - Greek immigrant children (GI) belonging to the second generation of immigrants in Sweden have been compared with Swedish children (S) and Greek children in Greece (G) regarding energy and nutrient intake. Twenty-four-hour recalls were obtained in the homes of the families. The mean energy intake was the same in all three groups and met the Swedish Nutrition Recommendations. The energy distribution for protein, carbohydrates and fat was also similar. The fat intake was far above the recommended level in all groups. The GI and the G group had a significantly higher mean daily intake of monounsaturated fatty acids than the S group (p less than 0.05 and p less than 0.001, respectively). Children aged four to eight years in the GI group had a significantly higher nutrient density of retinol, vitamin D, riboflavin, vitamin B6, calcium, iron, magnesium and sucrose compared to the G group, but compared to the S group they had a lower nutrient density of retinol, vitamin D, ascorbic acid, niacin, vitamin B12 and selen. The GI children consumed more milk than the G children but as much as the S children and they had started to use enriched low-fat milk in Sweden. In conclusion, the food quality in the GI group was better than in the G group and much the same as in the S group, and, with few exceptions, it met the Swedish Nutrition Recommendations. PMID- 1498512 TI - The urinary acylcarnitine profile in three cases of transient hyperammonemia of the newborn. PMID- 1498513 TI - Lipids and lipoproteins in cord blood: analyses of a Hispanic and Arab population. PMID- 1498514 TI - Parental attitudes towards discipline. PMID- 1498515 TI - How small is too small? A personal opinion. PMID- 1498516 TI - Surfactant as an immunogen: implications for therapy of respiratory distress syndrome. PMID- 1498517 TI - Clinical and electrophysiological reports in a case of early onset myotonia congenita (Thomsen's disease) successfully treated with mexiletine. AB - A sporadic event of myotonia congenita in a infant admitted to the Paediatric Clinic for frequent crises of apnoea, cyanosis, vomiting and difficult feeding is reported. EMG analysis was consistent with the dominant variety of myotonia congenita. Mexiletine therapy showed excellent results in reducing myotonic activity. It is worthwhile stressing that early symptoms may go unnoticed or may be misinterpreted and that information on the genetic form of the disease can be obtained also from the EMG analysis through a repetitive stimulation test. PMID- 1498518 TI - The primary empty-sella syndrome and diabetes insipidus in a child. AB - The empty-sella syndrome is uncommon in pediatric patients. Hypothalamic pituitary dysfunction is common in these patients but involvement of the posterior pituitary gland is very rare. We report a seven-year-old girl with empty-sella syndrome who first developed arginine-vasopressin deficient diabetes insipidus and then anterior pituitary gland deficiency. The empty-sella syndrome should be included among the causes of arginine-vasopressin deficient diabetes insipidus in pediatric patients. PMID- 1498519 TI - Role of human blood monocytes in up-regulation of lymphokine (interleukin-2) activated killer cell activity with cisplatin and FK-565. AB - The role of cisplatin (CP) and FK-565 in monocyte-mediated up-regulation of lymphokine-activated killer (LAK) cell induction by interleukin-2 (IL-2) was examined. Treatment of peripheral-blood mononuclear cells (PBMC) with CP or FK 565 in the presence of IL-2 resulted in a significant increase in LAK activity against NK-resistant Raji cells, as assessed by the 4-hour 51Cr release assay, depending on the dose of CP, FK-565 and IL-2. Up-regulation of IL-2-induced LAK activity by CP/FK-565 was significantly higher in whole PBMC as compared to PBMC depleted of monocytes. Addition of different numbers of monocytes to cultures of lymphocytes plus IL-2 along with CP or FK-565 resulted in a significant up regulation of LAK activity depending on the number of monocytes added. Pretreatment of monocytes for 2 h with CP or FK-565 before addition of lymphocytes plus IL-2 resulted in significant up-regulation of LAK activity as compared to untreated monocytes. Culture supernatant of CP- or FK-565-treated monocytes also significantly up-regulated IL-2-induced LAK activity of lymphocytes. The results of the present investigation suggest that up-regulation of LAK activity by CP and FK-565 in human PBMC is monocyte-mediated. Further, our data demonstrate that tumor necrosis factor and IL-1 play an important role in the up-regulation of LAK activity by monocytes that have been pretreated with FK 565 or CP. These results indicate that CP and FK-565 may be useful in modulating the immune response during treatment of neoplasia with IL-2 and LAK therapies. PMID- 1498520 TI - Signal transduction in activated natural killer cells and natural killer cells inactivated with sensitive targets. AB - We have recently demonstrated that the activation of NK cells involves a protein kinase-C (PKC)-dependent step as well as a phosphatidylinositol (PI)-linked signal transduction system. We have also shown that when NK cells are incubated with sensitive targets for up to 6 h they lose their lytic potential and require IL-2 to regain their lytic activity. PKC is involved in many cell processes such as the transduction of hormonal signals and the machinery of cellular secretion and is activated by diacylglycerol and by a number of phorbol esters, including phorbol myristic acid (PMA). To reinforce the role of PKC in NK-cell-mediated cytotoxicity, we first showed that NK-CMC is inhibited by two agents that inhibit PKC activation, staurosporine and sphingosine. Next, we showed that antibody dependent cellular cytotoxicity of NK-resistant targets was PKC dependent and Ca2+ dependent. Further, we showed that PMA plus ionophore alone could induce NK killing of resistant targets and that this killing was PKC and Ca2+ dependent. Finally, we contrasted the role of PKC in these activated cells to the role of PKC in cells that have been inactivated with a sensitive target, K562. We showed that PKC is not required for the IL-2-dependent reactivation of NK cells but that Ca2+ is required. To further determine what event in signal transduction is inactivated by K562, we showed that inactivated NK cells do not turnover PI in response to K562 stimulation. PMID- 1498521 TI - Population dynamics of natural killer cells and T lymphocytes in murine spleen and bone marrow during the development of erythroleukemia: the effect of indomethacin. AB - Quantitative and functional methods were used to assess changes in NK (ASGM-1+, nonblast, lymphoid) cells and cytotoxic/suppressor T (Lyt-2+) cells in the spleen and bone marrow (BM) of normal DBA/2 mice and/or mice bearing early (7 days)- and late (14 days)-stage erythroleukemia +/- concomitant oral administration of indomethacin. In normal mice, indomethacin increased ASGM-1+ cells in the spleen and BM by 7 days of continuous drug administration relative to control, while the numbers of Lyt-2+ cells in both organs remained unaltered. The presence of a tumor in untreated mice resulted, by 14 days development, in elevated numbers of ASGM-1+ cells in the spleen and BM. Lyt-2+ cells in the spleen increased transiently (7 days) in tumor-bearing (TB) mice and returned to normal levels by 14 days TB. No difference in either early- or late-stage TB was observed in the numbers of Lyt-2+ cells in the BM. In spleen and BM of TB mice, indomethacin increased ASGM-1+ cells by 7 days TB. ASGM-1+ cells returned to untreated levels by 14 days TB in both organs in spite of continued drug treatment. The numbers of Lyt-2+ cells in both the spleen and BM of 7 days indomethacin-treated TB mice were reduced relative to those of untreated TB mice. By 14 days TB, drug treatment had no effect on Lyt-2+ cell numbers in the spleen or BM. Spontaneous cytolytic activity of the spleen and BM did not always parallel changes in the numbers of ASGM-1+ cells, indicating the presence of late, immature, prelytic NK cells among the ASGM-1+ cell numbers. The results demonstrate that the numbers of NK and cytotoxic/suppressor T cells are markedly but differentially affected during tumor growth and/or time of exposure to indomethacin in an organ-specific manner. PMID- 1498522 TI - Effect of recombinant murine tumor necrosis factor on the generation of natural killer cells in bone marrow cultures. AB - We investigated the possible role of tumor necrosis factor-alpha (TNF-alpha) in the interleukin-2 (IL-2)-dependent generation of natural killer (NK) cells from bone marrow precursors. TNF-alpha synergistically augmented both cytotoxic activity against NK-sensitive targets and cell number at the end of the 7-day incubation period. After this time, NK activity was not induced by TNF-alpha in the absence of IL-2. The cytotoxic cells generated by IL-2 + TNF-alpha had the phenotype of mature NK cells, including expression of NK-1.1, asialo-GM1, Ly-5, LFA-1 and Thy-1. TNF-alpha was also able to up-regulate the mRNA expression for the IL-2 receptor alpha-chain (P55) as well as the mRNA expression of c-myc protooncogene. Blocking studies with monoclonal antibodies against the alpha chain P55 of the IL-2 receptor confirmed the functional role ascribed to IL-2 in the in vitro generation of NK cells from bone marrow cultures. Additional proliferation studies demonstrated that the up-regulation of c-myc protooncogene was associated with an increased uptake of thymidine. These data indicate that the TNF-alpha-induced increase of IL-2-dependent NK cell generation from bone marrow precursors was associated with an augmented proliferation and an up regulation of mRNA expression for IL-2 receptor and c-myc protooncogene. PMID- 1498523 TI - Diagnosis of peptic ulceration. PMID- 1498524 TI - Update on acid-peptic disorders. PMID- 1498525 TI - Epidemiology considerations in peptic ulcer disease. AB - Peptic ulcer disease is a common clinical problem. The lifetime risk of peptic ulcer disease is at least 10%. Millions of Americans are affected each year, imposing a major economic burden on the health care system. The overall hospitalization and mortality rates for peptic ulcer disease seem to have decreased substantially over the past few decades. There is much to suggest, however, that these changes were occurring even before effective medical therapy became available. In addition, other influences, such as increasing age of the population at risk, changes in smoking prevalence, and increasing use of nonsteroidal anti-inflammatory drugs, have impacted on the changing epidemiology of peptic ulcer disease. Hospitalization rates for patients with complications of peptic ulcer disease have remained relatively stable or, especially in the case of elderly women with gastric ulcers, increased significantly in recent years. Understanding the epidemiology of peptic ulcer disease will allow improved assessment of the effects of medical and surgical therapy and, hopefully, provide better clues to the etiology of this diverse group of diseases. PMID- 1498526 TI - Stress ulcer. AB - Stress ulceration is a recognized cause of morbidity and mortality in the critically ill patient. These superficial lesions occur in both the stomach and duodenum within hours after admission to a critical care unit. Although the pathogenesis of stress ulcer is not well understood, it is now established that a decrease in mucosal pH below 6.5 is essential for the induction of stress ulceration. This drop in mucosal pH can result from high luminal hydrogen ion (H+) concentration, increased permeability of the mucosa for H+, or defective neutralizing ability of the mucosa. Local and systemic factors that modulate mucosal blood flow are also important in the development of stress ulceration. It is estimated that 20% to 30% of patients with stress ulcer develop significant gastrointestinal bleeding that requires blood transfusion. The routine administration of H2-receptor antagonists has become standard practice in most intensive care units to prevent the development of stress ulcer and gastrointestinal bleeding, although in many cases their efficacy is unproven. Antacids are clearly effective and remain the gold standard with which alternative therapies are compared. The best treatment for stress ulceration is identification of the patient at risk and institution of prophylaxis. For patients who bleed from stress ulceration, conservative measures should include aggressive treatment of the underlying medical problem and neutralization of acid. PMID- 1498527 TI - [New understanding on apoplexy theory and traditional treatment method with integration of traditional and Western medicine]. PMID- 1498528 TI - [Traditional Medicine in Thailand]. PMID- 1498529 TI - [Clinical and experimental study of semen Persical decoction for purgation with addition in type II diabetes mellitus]. AB - This paper reported the results of clinical observation on a treatment with Semen Persical decoction for purgation with addition (SPDPA) in type II diabetes mellitus. The effective rate of SPDPA on 106 cases of noninsulin dependent diabetes mellitus (NIDDM) was 79%. The efficiency of SPDPA was equivalent to glyburide. From the experimental study, it can be concluded that SPDPA could reduce blood sugar and relieve symptom in diabetic patients and rats. Its mechanism may be due to improving secretion of insulin, inhibiting production of glucagon, repairing insular endocrine cell, increasing endocrine pellet of insular B cell and improving composition of hepatic glycogen. In traditional Chinese medicine theory, the mechanism of therapeutic action of SPDPA in diabetes mellitus is based on synergistic regulation of benefiting Qi and nourishing Yin, activating blood circulation to dissipate blood stasis and loosening the bowel to relieve constipation. PMID- 1498530 TI - [Determination of partially cellular and local immune function in patients with spleen deficiency syndrome]. AB - The immune function status as reflected by the peripheral blood OKT system T cell subset classification and the lymphocyte in vitro interleukin 2 (IL2) secretory function were determined in 30 patients with Spleen deficiency syndrome and 20 normal subjects in this study. Experimental results decreased cellular immune function and disturbance of immune regulatory mechanism in the patients. Its manifestations were decreased number of total T lymphocytes and helper T cells (Th), relatively increased suppressor T cells (Ts), abnormal rate of Th to Ts, no marked change of IL2 secretory function of T cell in vitro, increased SIgA level before stimulating with acid but marked decreased SIgA level after stimulating. All these suggest the compensatory stage of local immune function. PMID- 1498531 TI - [Effect of aging on the syndrome of essential debility and evil reality--an exploration on mechanism of senility by traditional Chinese medicine]. AB - Effect of aging on essential debility and evil reality was explored by an epidemiological investigation of clinical syndrome with TCM in 878 cases of middle and old-aged patients, inquiring into their relation of senility with visceral weakness and stagnation of Qi, blood stasis, and phlegm turbid. The results indicated that (1) several viscera, feeble and damaged, were the basis of senility, and the feeble kidney was the stress; (2) the syndrome of stagnation of Qi, blood stasis and phlegm turbid speeded up process of senility. The mechanism of feeble phenomena appeared in the middle-old aged patients is that with the rise of age in the patients observed there was interaction between the feeble visceral function and the syndrome of stagnation of Qi, blood stasis and phlegm turbid, that is, there was interaction between essential debility and evil reality. Essential debility may lead to evil reality and the latter will worsen essential debility. Thus, on repeating themselves in alternate cycles, a systemic hypofunction will be formed up to exhaustion. Therefore, "to nourish essential debility first and to purge evil reality second" should be considered as an essential direction of preparing anti-aging drugs in TCM. PMID- 1498532 TI - [Combined gu chi wan and spiramycin in the treatment of periodontal disease]. AB - The purpose of the present study is to evaluate clinical effect of the integrated traditional Chinese and western medicine in the treatment of periodontal disease. 90 patients suffered from mild to advanced periodontitis were divided into two groups. The gu chi wan (tooth firming pills) group was administered tooth firming pills 4 mg twice daily for 3-6 months combined with spiramycin 0.2 four times daily for 5 days and routine periodontal treatment. The spiramycin group, as control, was administered spiramycin 0.2 four times daily for 5 days combined with routine periodontal treatment. The clinical parameters: GI, PLI, PDI and serial radiographs were checked on the beginning of study and through 3, 6, 12, 24 months follow up study. The results showed that the GI and PDI of the gu chi wan group decreased significantly than the control group (P less than 0.001). The inflammatory recurrence rate was 33% in the control group and 12% in gu chi wan group and the serial radiographs demonstrated that a higher incidence of bone fill occurred in gu chi wan group than in the control group (P less than 0.01). PMID- 1498533 TI - [Influence of application-impulse stimulation treatment on airway's reactivity with asthma]. AB - The authors observed the effect of application-impulse stimulation treatment on 184 patients with asthma, using the main index of airway's reactivity, in a randomized, double-blind, placebo-controlled parallel study. The airway's reactivity of the treated group got improved significantly (P less than 0.001), but that of the control group was not changed sharply (P greater than 0.05). The airway's reactivity and clinical effect between the groups have significant meaning (P less than 0.001, P less than 0.001). The result suggests that application-impulse stimulation treatment is a safe and effective method for preventing and treating asthma. PMID- 1498534 TI - [Stimulative effect of electro-blunt-tip needle on the points of human skin and its analgesia in rats]. AB - The stimulative effect of electro-blunt-tip needle (a kind of electroacupuncture stimulating on the surface of skin point) on the 120 points of human skin was observed in 12 healthy volunteers. It was shown that the substitute typical electro-blunt-tip needle stimulator and its special pen-like electrode by a general electroacupuncture stimulator and a tape-like adjustable electrode and similar therapeutic effects. It was found in animal experiment that the pain threshold determined with rat tail flick analgesia method was raised by electroacupuncture and electro-blunt-tip needle, the optimal stimulating time being 10-20 minutes for both, the percentages of the maximal changing pain threshold being 206.6% and 175.4%, and the corresponding voltage being 2v and 7v respectively. PMID- 1498535 TI - [Flow cytometric analysis of the garlic oil effect on DNA content of cancer cell cycle]. AB - Flow cytometry (FCM) is a new technique developed in the recent decade. This technique may measure DNA content of 5000 cells per second and trace the dynamic changes in cell proliferation cycle and offer a hint for designing clinical treatment protocol, monitor prognosis and elucidate the mechanisms of antitumor drugs. The authors previous studies showed significant effect of garlic oil on prolongation of life expectancy and inhibition of tumor growth in mice. Using FCM the authors analysed the effect of garlic oil on cell cycle in S180 tumor cells, 2-6 hrs after single administration or multiple administration the cell number in S phase rapidly decreased, in G1 phase increased. This suggests garlic oil may blockade cells to progress from G1 phase to S phase and result in accumulation of cells in G1 phase and directly inhibit the synthesis of DNA and the cell cycle. Theoretical basis for clinical application was offered and some aspects of antitumor mechanism of garlic oil were elucidated. PMID- 1498536 TI - [Pharmacologic studies of antimotion sickness actions of ginger]. AB - The pharmacologic actions related to antimotion sickness effects of ginger (Zingiber officinale Roscoe.) were studied. There was no significant effect on parameters of rotatory movement-induced electronystagmogram of rabbit after intravenous (i.v.) infection of ginger juice. The low amplitude fast wave pattern of electrocorticogram of rabbit changed to high amplitude slow wave pattern after i.v. injection of ginger juice. Rabbit gastric contraction in situ was shortly suppressed after ginger juice i.v. administration. In the isolated rat fundus strip preparations, however, ginger juice reduced the spontaneous contractile frequency, and enhanced the spontaneous contractile amplitude, which was followed by inhibition. Ginger juice produced longitudinal contraction of the guinea-pig isolated ileum, which was followed by rapid tachyphylaxis. This contraction effect was not affected by hexamethonium and 5-HT, but could be inhibited by cold storage, hyoscine, morphine, diphenhydramine, promethazine and substance P desensitization. Naloxone could eliminate this inhibition produced by morphine. By using dose-response relationship plot, non-competitive antagonisms were observed between ginger juice and Ach and between ginger juice and histamine in isolated guinea-pig ileum. It is suggested that the pungent constituents of ginger release substance P from sensory fibres. The released substance P in turn either stimulates cholinergic and histaminic neurons to release Ach and histamine, respectively, or produces direct muscle contraction by activating M and H1 receptors correspondingly. It is proposed that after being excited by substance P, M and H1 receptors are inactive temporarily and unable to be excited by agonists, therefore, ginger juice exhibits anticholinergic and antihistaminic action. Ginger juice produces antimotion sickness action possibly by central and peripheral anticholinergic and antihistaminic effects. PMID- 1498537 TI - [Treatment of lupus erythematosus with integrated traditional Chinese medicine and Western medicine]. PMID- 1498538 TI - [Treatment of severe chronic hepatitis B by combination of traditional Chinese medicine and Western medicine therapy--with an analysis of 122 cases]. AB - This paper is a summary report of treatment of 122 cases of severe chronic hepatitis by combination of TCM and WM therapy. Among them, 44 cases were in their early stage of disease, 66 in their intermediate stage, and 12 in their advanced stage. They were treated by basic therapy with hepatic cell growth factor (HGF) added to some of them. The patients were divided into two groups, one receiving treatment of blood-cooling and detoxifying Chinese herbs, the other receiving treatment of heat-clearing and detoxifying Chinese herbs. The treatment was effective for 52 cases, and ineffective in 70 cases. Values of serum bilirubin (SB) and prothrombin activity (PA) and the time of initial consultation had marked influence on their prognoses. No difference was found in total mortality between the two groups, also no difference was found in mortality between the former and latter group with or without the addition of HGF at the early stage of disease. The survival rate of the former group was significantly higher than that of the latter one with HGF added at their intermediate stage of disease, which were 60% and 14.7% respectively, P less than 0.01. The conclusion is that as diagnosis and treatment were based on the Syndrome Differentiation of patients at intermediate stage of disease, Chinese herbs will be effective in many ways such as lowering and eliminating jaundice, improving symptoms and signs, preventing and curing complications, curing coexisting diseases, and repairing pathological lesions. PMID- 1498539 TI - [Modulating effects of extractum semen Persicae and cultivated Cordyceps hyphae on immuno-dysfunction of inpatients with posthepatitic cirrhosis]. AB - The treatment of 65 cases (with 20 cases in the control group) of patients with post-hepatic cirrhosis by Extractum Semen Persicae (ESP) and cultivated Cordyceps Hyphae (CH) was reported, and the adjustment of the disorders of both cellular and humoral immune functions was investigated. The results indicated apparently that the restrained cellular immune function, among which the rate of lymphocyte transformation, the NK cell's function, CD8+ and CD4+ cells in the patients' group were lower than those in the healthy group. The CD8+ cell count was positively correlated with lymphocyte transformation rate and the humoral immune hyperfunction revealing that the levels of IgG, IgA, ssIgA and CIC of the patients were abnormally higher than those of healthy subjects, while level of C3 was negatively correlated with that of CIC. After the treatment, rate of transformation, function of NK cell, CD8+, CD4+ cells and the ratio of CD4+/CD8+ improved; levels of IgG, IgA, ssIgA and CIC reduced, while those of C4 and C3 rose. These results revealed the ESP and cultivated CH could modulate the cellular immune function, inhibit the humoral immune hyperfunction and increase serum complement level in patients with post-hepatitic cirrhosis, which were correlated to the improvement of hepatic function. Disorder of immune function was one of the important causes of liver cell necrosis, inflammatory cell infiltration and fibroplastic proliferation. The results showed that the drugs are of some value in the treatment of patients with post-hepatitic cirrhosis. PMID- 1498540 TI - [Characteristics of clinical pathology and changes of liver function in blood stasis syndrome in liver diseases]. AB - The experimental study on 30 patients of the Blood Stasis Syndrome of liver diseases was discussed in this paper. Two characteristics were found. One was the pathological feature which manifested as follows: (1) DIAGNOSIS: the Blood Stasis Syndrome of liver disease was mainly diagnosed in the chronic active hepatitis and the early stage of cirrhosis of liver, while that of non-Blood Stasis was mainly observed in the chronic persistent hepatitis (P less than 0.01); (2) Pathological change: The histological changes such as piecemeal necrosis, bridging necrosis, the destruction of limiting plate, eosinophilic change, etc. It was more obvious in the Blood Stasis group than that with non-Blood Stasis Syndrome (P less than 0.01), (3) The manifestation of Blood Stasis Syndrome was not in parallel with the severity of the liver disease. The another characteristic was the changes of liver function, which expressed more markedly in the Blood Stasis group with higher level of SGPT, lower ratio of A/G and increased globulin, they were more obvious than that in non-Blood Stasis group (P less than 0.01). PMID- 1498541 TI - [Diagnosis on blood stasis in viral hepatitis by computer multi-criteria analysis -an analysis of 63 cases]. AB - This study is based on the criteria for diagnosis of Blood Stasis formulated by the international conference held in Beijing in 1988. The patient that has one, two, three, and over four items could be diagnosed as I-, II-, III-, IV-degree hepatic Blood Stasis respectively. The data of pathologic findings from liver biopsy, nail-fold microcirculation, blood rheology, hepatogram, B-ultrasonography and blood biochemical examination were stored in computer to carry on single and multiple factor analysis in order to evaluate these indexes in the diagnostic value of hepatic Blood Stasis. Stepwise regression analysis formula was used to determine the severity of Blood Stasis. By substitute related data into the formula, mathematical model of hepatic Blood Stasis was compared with clinical Syndrome Differentiation, it revealed that 59 cases were coincided with each other (93.6%). According to numerical value, the increase and decrease of the pre and posttherapy, the curative effect of promoting blood circulation to remove Blood Stasis could be determined to provide some references for diagnosis and treatment of hepatic Blood Stasis and prevention and treatment of hepatic fibrosis. PMID- 1498542 TI - [Ischemic apoplexy treated with acupuncture using the principle of replenishing qi and promoting blood circulation]. AB - 32 cases of ischemic apoplexy were treated by acupuncture using the principle of replenishing Qi and promoting blood circulation. The clinical efficacy and the change of nail-fold microcirculation and hemorheology before and after the treatment were observed. RESULT: The total effective was 93.75%. Before the treatment, the microcirculation of nail-fold was markedly abnormal, and the criteria of hemorheology was abnormally elevated. But after the treatment, together with the recovery of nail-fold microcirculation and hemorheology, the clinical symptom and sign of the patients also improved. Thus it showed that acupuncture method had the function of changing the microcirculation and the hypercoagulability of the patients' blood, further promote the recovery of the function of affected cerebral tissue. PMID- 1498543 TI - [Determination of blood hormone levels in patients with "spleen deficiency" syndrome after major operations]. AB - The character of "Spleen Deficiency" (SD) Syndrome was evaluated by determination of the blood levels of various gastroenteropancreatic hormones and thyroid hormone. Patients of SD group were diagnosed clinically by Syndrome Differentiation, and those of the normal group were volunteer blood donors. RIA was used to determine all the hormones except T3RUR. RESULTS: TT3, FT3 of the SD group were very significantly lower than that of normal group (P less than 0.001). The levels of rT3 in SD group were significantly higher than normal control (P less than 0.05). For TT4, T3RUR and FT4, there were no significant differences between the two groups. Among the gastroenteropancreatic hormones, gastrin in the SD group was significantly lower than that of the normal group (P less than 0.01), motilin was very significantly higher (P less than 0.002). The value of pp was similar in the two groups, under physiological conditions, however, in adults the hormone tended to increase with age. Since the average age of patients in the SD group was 54.9, and that of the normal group was 38.5, remarkably lower values were seen in the SD group. Other hormones such as VIP, SST, glucagon and insulin were of no significant difference between the two groups. The result showed that thyroid hormone and some of gastroenteric hormones in the blood of patients with SD after major operations were quite different from normal, and was common to patients with general SD Syndrome, with low T3 syndrome.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1498544 TI - [Antagonistic effect of re du qing on damage of hepatocytic microsomes in rabbits with endotoxin-induced disseminated intravascular coagulation]. AB - In this study, the generalized Shwartzman reaction of rabbit induced by endotoxin of Escherichia Coli was built as DIC models. The experiment showed that the levels of lipid peroxide (LPO) in the hepatocytic microsomes of model group were increased significantly, whereas the cytochrome P-450 (Cyto. P-450) contents and aniline hydroxylase activities were obviously decreased. In the Re Du Qing (RDQ) group and dexamethasone group the decrease of LPO in hepatocytic microsomes as well as the reduction of Cyto. P-450 contents and aniline hydroxylase activities were alleviated. Furthermore, the correlation analysis indicated a significant negative correlation between levels of LPO in microsomes and the Cyto. P-450 contents as well as aniline hydroxylase activities. This study indicates the LPO may play an important role in the damage of hepatocytic microsomes and RDQ could prevent hepatocytic microsomes from injury of rabbits with endotoxin-induced DIC. PMID- 1498545 TI - [Experimental study on yiqi-huoxue therapy of liver fibrosis]. AB - The experimental hepatic fibrosis was treated with YiQi (reinforcing Qi, YQ) Huoxue (activating blood circulation, HX) principle which was consisted of astragalus membranaceus, Ligusticum wallichii, paeonia lactiflora, etc. After stimulation with CCl4 over four months, the Wistar rat developed liver fibrosis. Rats were divided into the normal control, the toxifying control, YQHX group and HX group. The experimental period lasted over four months. RESULTS: (1) Mortality of animal: Both toxifying control and HX group reached 50%, while YQHX group was 16% only. These results suggest that YQHX agents could strengthen the body resistance; (2) The determination of serum SGPT: The mean levels in toxifying control were 39.3 +/- 39, in HX group 43.7 +/- 12.9, while in YQHX group 29.0 +/- 7.6 (units/Lserum). These results indicated that YQHX agents had the function of protecting the liver and lowering the activity of SGPT (P less than 0.01); (3) Measuring the contents of hepatic collages: The mean levels in toxifying control was 38.9 +/- 3.3 (mg/g liver), while in HX group and YQHX group 28.7 +/- 2.2 and 22.7 +/- 1.1 (mg/g liver) respectively. The results indicated that the YQHX agents had the best results in treating hepatic fibrosis; (4) Observation with hepatic histopathology: The degree of hepatocyte degeneration and necrosis in YQHX group was milder than that in toxifying and HX group. These observations revealed that YQHX agents possessed the function of protecting liver. There was severe liver fibrosis in toxifying control, but the degree of liver fibrosis in YQHX group was significantly milder than that in toxifying control.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1498546 TI - [Immunologic parameters used in antitumor study of traditional Chinese medicine]. PMID- 1498547 TI - [Development of traditional Chinese medicine and pharmacology in Hong Kong]. PMID- 1498548 TI - [General survey and prospect of clinical uses of shengmaisan]. PMID- 1498549 TI - [Perioperative hemostatic problems in children]. AB - During childhood preoperative coagulation diagnosis is performed to prove or to rule out an inborn coagulation disorder or an acquired v. Willebrand disease. The coagulation system of the newborns differs considerably from that of the adults as well as the time in which the single parameters reach adult values. Reducing the coagulation screening to the determination of aPTT and Quicktest neglects severe hemostaseological disorders easily, e.g. v. Willebrand disease which often in childhood is to be observed and often combined with normal aPTT values. Probably sometimes children affected with hypertrophy of the adenoids have temporary aPTT prolongations combined with normal values for the other coagulation parameters possibly due to lupus inhibitors. When children with deficiencies of coagulation factors need high doses of coagulation concentrates the number of laboratory controls may be reduced by determination on recovery and half-life period some times before. PMID- 1498550 TI - Blood component processing technique and plasma quality. AB - To maintain a closed system during the preparation of blood components, including the removal of buffy coat, many centers use a quadruple blood bag additive solution system which in this study has been reduced to a cheaper triple bag system. The buffy coat and plasma were after centrifugation transferred to the first satellite bag and, after a second spin, the plasma separated from the buffy coat was transferred to the second satellite bag and stored for a fortnight at 4 degrees C. This resulted in a statistically significant increase in platelet factor 4 and elastase activity levels. No significant changes were found in the levels of C1-esterase inhibitor and kallikrein inhibiting activity, thrombin antithrombin complexes, soluble fibrin, fibrinopeptide A and spontaneous proteolytic activity. The changes observed must be regarded as clinically insignificant. The platelet count is low enough to meet the requirements for platelet poor plasma. Using this blood component separation technique, one can reduce the CPD/additive solution 4-pack blood bag system to a less expensive 3 pack blood bag system. PMID- 1498551 TI - Biocompatibility of synthetic oxygen carriers and fluorosurfactants. AB - A system for testing the biocompatibility of synthetic oxygen carriers is described including tests of hemolysis, complement activation and proliferation of cell lines or lymphocytes. Of 17 surfactants tested in this system, 6 were compatible in all tests while the other compounds showed individually differing patterns of incompatibility. We conclude that, in order to conduct a meaningful screening, a series of different assays has to be applied. In addition to our system, further assays, covering cytokine induction and phagocytosis should be attempted. PMID- 1498552 TI - [The elimination of carboxyhemoglobin--gender-specific and circadian effects]. AB - We investigated sex-specific and circadian variations of carboxyhemoglobin (COHb) elimination in healthy volunteers. COHb elimination follows an exponential function with a baseline found in nonsmoking women at 1.72% and in nonsmoking men at 1.79% COHb saturation. During the day, the elimination half-life time (t1/2), determined by eleven hourly samples after stopping smoking was significantly (Wilcoxon-test, p less than .01) shorter in women (3.2 +/- .4 hours, mean +/- standard deviation, n = 7) than in men (4.5 +/- 0.4, n = 6). During the night, too, t1/2 calculated from 2-point measurements after the smoking halt was significantly (Wilcoxon-test, p less than .05) shorter in women (4.3 +/- 1.1, n = 4) than in men (8.0 +/- 1.6, n = 5). In men, t1/2 during the night was significantly longer (p less than .01, Wilcoxon-test) than during the day. The day/night difference may be caused by reduced alveolar ventilation during sleep. Less muscle mass and, therefore, less myoglobin as a depot for carbon monoxide may account for the shorter half-life time of carboxyhemoglobin in women. We conclude that these variations of COHb-elimination should be taken into account when a smoking halt is advised, for instance, preoperatively. PMID- 1498553 TI - Selection of unrelated bone marrow donors: does the current procedure warrant complete MHC class II identity? AB - Bone marrow transplantation from unrelated donors is being used increasingly for the treatment of patients with leukemia and several other hematologic disorders. Selection of unrelated bone marrow donors currently relies on serological HLA identity and negative mixed lymphocyte reactions between donor/recipient pairs. As serological HLA-DP typing is not feasible, we used the HLA-DPB1 oligonucleotide typing method to investigate whether the current selection procedure can guarantee complete MHC class II identity. In 40 consecutive patients, one third (62/193) serologically HLA-A, -B, -C, -DR and -DQ identical donors were found to be MLC negative with a relative response below 5%. HLA-DPB1 oligonucleotide typing of these MLC negative donors revealed that again only one third (20/62) was also identical for DP with their presumptive recipients. In the majority of pairs a disparity in graft-versus-host direction or in host-versus graft direction of at least one allele was seen. These data indicate that in spite of the strict MLC criteria used, the current procedure did not warrant complete MHC class II identity. This implies that oligotyping for DPB1 can improve matching and should be introduced for typing of volunteers. We speculate that DP differences may contribute to the higher incidence of graft-versus-host disease or graft rejection in unrelated transplants. PMID- 1498554 TI - Automated measurement of cell destruction: the Patimed system in comparison with conventional HLA typing and the cell mediated lympholysis test (CML). AB - The key role of HLA polymorphism in the pathogenesis of many diseases and in determining compatibility in transplantation makes it desirable to employ automated systems for identifying HLA polymorphism. For more than one year we have used the photometer system Patimed commercially available from the Leica company. We compared the results of the conventional cell-mediated lympholysis test and conventional serological HLA typing with the results obtained by the Patimed system. Despite some good preliminary results it would be premature, in our opinion, to recommend the Patimed system for routine assessment of killer cell activity whereas we can definitely recommend the Patimed system to define HLA class I and class II molecules serologically for research or routine purposes. PMID- 1498555 TI - [Gene amplification with PCR and sequence-specific HLA oligotyping]. AB - Genetic polymorphism in the HLA-class II region has been identified by the analysis of the polymerase-chain reaction (PCR) products using sequence-specific oligonucleotide (SSO). The PCR-SSO method permits precise and direct analysis of allelic variations with as little as 1 microgram of genomic DNA. The standardized, uniform hybridization and critical wash protocol of the Eurotransplant-typing kit [2] enables HLA-typing independent of gene expression and lymphocytes quality. One of the advantages of this technique is that the definition of subtypes is much better than is typing by serology. PMID- 1498556 TI - One year's experiences with two different image analysis systems for automated reading of the contrast fluorescence test. AB - We have tested two different personal-computer based color image analysis systems for automated reading of the microlymphocytotoxicity test (LCT) for HLA-A,B,C typing and screening. Over 17,000 single LCT-reactions were prepared using the simultaneous double fluorescent variant of the LCT (contrast fluorescence test, CFT). All tests were read visually by experienced laboratory staff members. For image analysis, an automated scanning system was used. In a first step, reactions were recorded on a videotape recorder using a color(CCD)-video camera. In a second step, the recorded reactions were analyzed with the two different image analysis systems by specifically developed programs. Good correlation (r = 0.89) of the score values assigned by digital image analysis with the visual tray reading was obtained. Since also the other main performance characteristics of the prototype system (throughput, reliability, compatibility) were acceptable for routine application, we may conclude that digital image analysis is a feasible and very interesting new technique for automated evaluation of the LCT. PMID- 1498557 TI - [Changes in thrombocytapheresis concentrations caused by leukocyte depletion with polyester filters]. AB - We studied platelet loss, leukocyte depletion, T/B-cell-ratio, platelet morphology and platelet function (aggregation, hypotonic shock reaction, retention and retraction) prior to and after filtration through two different polyester filters (Sepacell PL-5A, Pall PL100) as well as the posttransfusional platelet increment 1 h after transfusion in 8 pairs of single donor platelet concentrates (Cobe Spectra, Fresenius AS 104). Leukocyte depletion was effective (greater than 99.9%) and platelet loss acceptable in both filters, all tests showing no indication of a diminished platelet function by filtration. PMID- 1498558 TI - Effective derosetting of mononuclear cells isolated by immunomagnetic beads. AB - A rapid and effective method for the derosetting of peripheral mononuclear cells (PMNC) isolated by CD8 monoclonal antibody (MoAb) coated immunomagnetic beads (IMB) is described. PMNC are positively selected and enriched by CD8-IMB and then derosetted from the IMB by a polyclonal antibody (PoAb) preparation against mouse Fab. Our experiments confirm the feasibility of this method with a high derosetting efficiency. PMID- 1498559 TI - Filtration of buffy coat free red cell concentrates in additive solution. AB - Leukocyte poor RCC's (LP-RCC) are indicated in chronically transfused patients in order to prevent non-hemolytic transfusion reactions and HLA alloimmunization. In this study buffy coat free red cell concentrates (BCF-RCC) in additive solution (SAG-M) stored for four weeks were leukocyte depleted by filtration with three different filter systems (Erypur Optima (E), Sepacell R500 B (S) and, Pall RC, 50 TM (P)). The BCF-RCC's were prepared using 'bottom and top (BAT)' systems and automatic separation containing about 20% leukocytes and 5% platelets of fresh whole blood. The leukocyte concentration could be reduced to less than 5 x 10(6) per RCC with all filter systems equally: Leukocytes/RCC's: E .58 +/- .94, S .36 +/- .55, P .55 +/- .69 x 10(6). The leukocyte depletion was even in case of filtering two RCC's through one filter (double filtration) efficient enough in order to keep leukocyte contamination below the 'critical immunogenic load for leukocytes (CILL)'. But significant differences concerning the damage of red cells (free hemoglobin, LDH, HBDH) were measured which were even considerable: free hemoglobin E = 3.69 +/- 2.28, S = 1.31 +/- 1.24, P = 3.58 +/- 2.34 g/l. Double filtration was only performed with filter system S showing the best blood compatibility. But the second BCF-RCC also showed considerable hemolysis. Therefore, double filtration of RCC's only seems to be indicated under optimal conditions with blood compatible filters for selected patients. Bed side filtration cannot be recommended because of the risk of hemolysis that makes quality control necessary.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1498560 TI - The effect of posture and environmental temperature on cardiovascular reflexes in normal subjects and diabetes mellitus. AB - This study was undertaken to determine the effects of environmental temperature (17 degrees C or 27 degrees C) and posture on heart rate variability during forced sinus arrhythmia (deep breathing), and of environmental temperature on the heart rate and blood pressure responses to standing, and to the cold pressor test. A group of non-diabetic young subjects (23 +/- 5 years) and a group of older diabetic patients (54 +/- 15 years) were studied. At 27 degrees C, supine resting heart rate and systolic blood pressure were lower than at 17 degrees C in both diabetic and non-diabetic subjects, and heart rate variability was lower than at 17 degrees C in the non-diabetic subjects (p less than 0.01) with seven of 17 abnormal or borderline results (all seven subjects had normal values at 17 degrees C). Room temperature had no effect on supine heart rate variability in the diabetic patients. At 27 degrees C heart rate variability in the upright posture was significantly greater than supine (p less than 0.001) in the non diabetic subjects. In the diabetic subjects, heart rate variability when standing at 17 degrees C increased such that five patients classified as abnormal when supine had normal values when upright. A similar pattern was observed at 27 degrees C, although only those with normal heart rate variability showed an increase on standing. Room temperature had no effect on the responses to the cold pressor test, or the blood pressure responses to standing, although the heart rate response was greater in both groups at 27 degrees C. This study shows that care should be taken to standardize the conditions under which heart rate variability is determined. PMID- 1498561 TI - Parkinson's disease and weight loss: a study with anthropometric and nutritional assessment. AB - In order to investigate a putative weight loss in patients with Parkinson's disease, an anthropometric and biochemical study was undertaken. We compared body weight and indexes of fat [body mass index (BMI), tricipital skinfold] and lean [midarm muscle area (MMA), calf circumference] mass in men and women suffering from idiopathic Parkinson's disease with normal controls. We found that women suffering from Parkinson's disease exhibited a significant weight loss (-8.5%) and decreased calf circumference when compared with controls. A decrease (-4.3%) in total body weight was also found in men with Parkinson's disease but the difference did not reach the level of significance. Protein biochemical markers of nutritional status (albumin, prealbumin, retinol binding protein, transferrin) were normal in Parkinson's disease patients. The present study demonstrates the occurrence of weight loss in a large population of patients with Parkinson's disease. The putative mechanisms involved in the weight loss are discussed. PMID- 1498562 TI - Estimation of noradrenaline concentrations in the axoplasm of noradrenergic neurones in man. AB - The plasma concentrations of noradrenaline (NA) and its primary neuronal metabolite, dihydroxyphenylglycol (DOPEG), were examined during graded orthostasis and NA infusion in 13 healthy subjects to estimate the NA concentration difference between the site of neuronal DOPEG formation and that in plasma. Stimulation of NA release by graded orthostasis resulted in similar absolute increments in plasma NA and DOPEG with both plasma concentrations being dependent on the degree of orthostasis. The mean value of the delta DOPEG/delta NA ratio amounted to 0.999 (0.745; 1.341). NA was infused i.v. during two consecutive 30-min periods at constant rates of 0.43 and 0.86 nmol kg-1 min-1, respectively. This infusion resulted in a delta DOPEG/delta NA ratio of 0.048 (0.036; 0.064) for the first and 0.078 (0.067; 0.090) for the second infusion period (p less than 0.01). For each individual subject, the factor quantifying the NA concentration difference between the site of neuronal DOPEG formation and plasma was calculated from the square root of the ratio of 'delta DOPEG/delta NA during orthostasis to delta DOPEG/delta NA during the low rate of NA infusion'. The average NA concentration at the site of neuronal DOPEG formation (i.e. the axoplasm of noradrenergic neurones) was found to be 4.6-fold higher than that in plasma. PMID- 1498563 TI - Parasympathetic hyperresponsiveness and bradyarrhythmias during apnoea in hypertension. AB - Voluntary end-expiratory apnoea in a 23-year-old asymptomatic mild hypertensive patient consistently elicited bradyarrhythmias (complete heart block and sinus pause) and sympathetic activation to muscle blood vessels, indicating simultaneous sympathetic and parasympathetic activation during apnoea. The sympathetic bradyarrhythmic response to apnoea was potentiated by hypoxia and eliminated by atropine. Baroreflex activation also attenuated the bradycardic response to apnoea. A 43-year-old hypertensive patient with sleep apnoea also exhibited bradyarrhythmias (sinus arrest for up to 10 s) and a fall in perfusion pressure to less than 50 mmHg during episodes of sleep apnoea. These cardiovascular changes were associated with a reduction in oxygen saturation to levels as low as 35%. Neither patient was on any medication. Simultaneous sympathetic and parasympathetic activation during episodes of apnoea may predispose to cardiovascular catastrophe. These chemoreflex mediated autonomic changes are inhibited by baroreflex activation. We propose that patients with impaired baroreflexes (patients with hypertension or heart failure and premature infants) may be especially susceptible to excessive autonomic responses to chemoreflex stimulation during periods of apnoea. In these patient groups, bradyarrhythmias, hypoxia, hypoperfusion and sympathetic activation during apnoea may predispose to sudden death. PMID- 1498564 TI - Gender related differences in the cardiovascular responses to upright tilt in normal subjects. AB - The heart rate and blood pressure responses to head-up tilt of 80 degrees was studied in 20 normal men and 21 normal women aged 20-50 years (mean age 31.1 +/- 7.1 years). The heart rate increase in females during tilt was 73% that of males, whereas the increase in diastolic pressure during tilt was 29% of males. Expressed in relation to values obtained supine, heart rate increases on average 30.3% in men as compared to 21.5% in women whereas diastolic pressure increases by 15.2% in men as compared to an increase of only 4.3% in women. The data indicates that the cardiovascular response of normal females to upright tilt differs significantly from that of normal males. This attenuated responsiveness to orthostasis in women relative to men may predispose women to postural insufficiency and may account for the predominance of symptomatic women with clinically mild dysautonomia. PMID- 1498565 TI - Presence of neuronal cell bodies in the sympathetic pressor areas of dorsal and ventrolateral medulla inhibiting phrenic nerve discharge in cats. AB - To examine whether neuronal cell bodies (perikarya) in the pressor areas of dorsal medulla or ventrolateral medulla also modulate respiratory function, phrenic nerve activity was monitored and correlated with the pressor response in chloralose-urethane anaesthetized cats. The animals were paralyzed and artificially ventilated maintaining the end-tidal fractional concentration of CO2 at 0.04-0.05. The same pressor point in the dorsal or ventrolateral medulla was stimulated electrically (rectangular pulse of 20-200 microA, 80 Hz and 0.5 ms) and then chemically (0.25-0.5 M sodium glutamate, 80-200 nl). Areas producing pressor effects in either the dorsal or ventrolateral medulla produced a current dependent decrease of phrenic discharge. The decrease in Pna was significant when the electrical current reached 50 microA or above. It occurred immediately before the onset of increase in blood pressure. Injection of glutamate to the same pressor point in either the dorsal or ventrolateral medulla produced a similar decrease in phrenic nerve activity. The results suggest that in the pressor areas of dorsal and ventrolateral medulla there are neuronal perikarya that can increase systemic arterial pressure and inhibit phrenic nerve activity. Whether the same or separate neurones are responsible for these responses is to be determined. PMID- 1498566 TI - Blood flow velocity waveform in the common carotid artery and its analysis in elderly subjects. AB - We investigated common carotid artery blood flow in 99 elderly nursing home residents using an ultrasonic quantitative blood flow measurement system. Systolic velocity and end-diastolic velocity were obtained from the waveform and classified, using the end-diastolic/systolic volume as Type A which is normal flow (greater than 20% bilaterally), Type B which is unilateral decreased flow (less than 20% unilaterally), Type C which is bilateral decreased flow (less than 20% bilaterally), Type D which is Type C plus a saw tooth pattern and Type E which is no diastolic pattern, i.e. a value of 0 unilaterally or bilaterally. Five per cent of subjects showed Type A of blood flow velocity waveform (normal flow pattern) and about 40% showed Type E (no diastolic pattern). The subjects were divided into three groups according to blood flow velocity waveform. Groups 1, 2 and 3 showed Types A or B, C or D, and E, respectively. The total blood flow volume and mean blood flow velocity of Group 1 were significantly higher than those of Groups 2 and 3 in both the supine and sitting positions. Although both total blood flow volume and mean blood flow velocity of Group 1 decreased significantly in postural change, those of Groups 2 and 3 did not change. These results suggest that total blood flow volume and mean blood flow velocity decrease in proportion to changes in the blood flow velocity waveform. PMID- 1498567 TI - Muscle chemoreflexes and exercise in humans. AB - This review focuses on the role afferent nerves from the contracting muscles play in linking muscle metabolism to the cardiovascular adjustments during exercise by means of a 'muscle chemoreflex'. In the 1930s Alam and Smirk provided the first clear evidence that human (and animal) skeletal muscles are innervated by chemosensitive afferents that can evoke increases in arterial blood pressure. They proposed that the purpose of the increase in pressure was to improve blood flow to the active muscles. Subsequent studies have identified the slowly conducting group IV afferents as the major class of fibres participating in the sensory arm of this reflex. Most of these fibres travel via the dorsal roots to the ipsilateral spinal cord where they synapse in the substantia gelatinosa and release substance P or other peptide transmitters. The second order (or higher) neurons cross to the contralateral side of the spinal cord and travel rostrally to stimulate brainstem cardiovascular centres and increase arterial pressure. Current evidence favours the concept that substances associated with muscle acidosis provide the stimulus to the afferents. In humans, chemosensitive afferent activation causes a marked increase in vasoconstrictor efferent muscle sympathetic nerve activity. It is unclear if the muscle chemoreflex improves blood flow to 'underperfused' active muscles by augmenting arterial pressure, or if the increase in sympathetic outflow restrains metabolic vasodilatation to regulate arterial blood pressure during activities like running or cycling. PMID- 1498568 TI - Argon laser lesions of the retina; occurrence and origin of macrophages. AB - Macrophage infiltration is frequent in the early stages of various proliferative eye disorders, including subretinal neovascularization. In this study, we set out to establish the origin of macrophages found in an animal model of laser-induced subretinal neovascularization. One primate received several intravenous injections of a colloidal carbon suspension. We then applied standard argon laser lesions to the retina of both eyes, which were enucleated eight days later and sectioned serially for histological examination. A quantitative estimate of carbon-laden and non-laden leukocytes was made based on morphological criteria. Mononuclear leukocytes accumulated in the laser lesions and the percentage of carbon-laden mononuclear leukocytes in relation to the total leukocyte number was higher in the extravascular area of the laser sites than in the systemic circulation. These findings indicate that the majority of mononuclear leukocytes that accumulate at the sites of laser lesions are derived from the systemic circulation. PMID- 1498569 TI - The safety and efficacy of topical norfloxacin compared with placebo in the treatment of acute, bacterial conjunctivitis. The Norfloxacin-Placebo Ocular Study Group. AB - Two hundred and eighty-four patients with acute conjunctivitis were enrolled in a double-masked study comparing norfloxacin ophthalmic solution with placebo. The proportion of patients who were clinically improved after 5 days treatment was 88.1% in the norfloxacin group and 71.6% in the placebo group (p less than 0.01). The proportion of patients who had all organisms eradicated, including the coagulase-negative staphylococci, after two to three days treatment was 52.7% for norfloxacin and 23.9% for placebo (p less than 0.01) and 64.7% and 26.3% (p less than 0.01) respectively when the coagulase-negative staphylococci were not included. Adverse experiences occurred in 4.2% of the patients receiving norfloxacin compared to 7.1% of the placebo patients. None of the adverse experiences was serious. PMID- 1498570 TI - Dacryo-fornix-rhinostomy with two flaps. AB - The two most frequent sites of obstruction of the lacrimal pathways are under the lacrimal sac, in the ductus lacrimonasalis, and over the lacrimal sac, in the canaliculi. The obstruction of the first type already has a satisfactory solution with the different forms of dacryo-cysto-rhinostomies. Obstruction of the second type has a satisfactory resolution only in a limited number of cases. For patients in whom current treatment methods are unsuccessful, a technique of dacryo-fornix-rhinostomy is presented, consisting in opening a new pathway between the infero-medial conjunctival cul-de-sac and the atrial part of the nasal cavity. A piece of bone is removed from the antero-lateral wall of the atrium nasi, and the bottom of the infero-medial conjunctival fornix is opened to the precedent wound. The exposed nasal mucosa is cut into two flaps, one being sutured to the posterior lip, and the other to the anterior lip of the conjunctival wound. A conformer is maintained in the new path for several weeks. The new path has an almost vertical trajectory, making the flow of tears very easy. Blinking and the movements of the eyes have a pumping effect. PMID- 1498571 TI - Choroidal angiography with indocyanine green dye: absorption and fluorescence techniques. AB - The results of choroidal indocyanine green (I.C.G.) angiography by the absorption and fluorescence techniques are compared. Both techniques were done using the same apparatus, a modified fundus camera, an image intensifier coupled to a solid state video camera and a U Matic video recorder. Both were performed with the same dye dilution in the same patients, at a 24-hour interval. The light source was the unmodified 50 Watt halogen light bulb of the fundus camera. The angiograms obtained by the absorption and the fluorescence techniques refer to the same chorioretinal area and the same angiographic phase. Comparison of all the angiograms shows that I.C.G. fluorescence angiography provides a better resolution of choroidal vascular details than the absorption technique. PMID- 1498572 TI - Binocular vision regained after monocular traumatic aphakia by wearing contact lenses. AB - In this study 35 patients with monocular traumatic aphakia were enrolled to document the degree of binocular vision gained by optical correction with contact lenses. The most important factors in achieving binocular vision were the interval between formation of the traumatic cataract and surgery and between the operation and starting wearing contact lenses. There was a statistically significant correlation between these two intervals and the achievement of near stereopsis and normal visual acuity. PMID- 1498573 TI - Simultaneous bilateral "malignant glaucoma" attack in a patient with no antecedent eye surgery or miotics. AB - Malignant glaucoma is a term commonly used to describe a condition characterized by a sudden increase in intraocular pressure, usually occurring after eye surgery. This report describes a case of malignant glaucoma simultaneously presenting in both eyes, with no antecedent eye disease, medication or surgery. As far as we know this is the first report of spontaneous bilateral glaucoma. Both eyes were operated on according to the technique described by Chandler et al. (1), and the condition was solved. We suggest that, despite its rarity in eyes with no antecedent disease or ocular therapy, a surgeon should be aware of this condition. PMID- 1498574 TI - Chronic postoperative endophthalmitis caused by Propionibacterium acnes. AB - Persistent intraocular inflammation after cataract surgery with intraocular lens implantation is acquiring importance. Frequently, chronic uveitis or the "toxic lens syndrome" have to be differentiated from bacterial infection. This report describes five cases with chronic postoperative endophthalmitis where the anaerobic bacterium Propionibacterium acnes was found to be the causative organism. Adequate anaerobic culture media and proper sampling from the area around the lens haptics are the most important requirements for the detection of P. acnes. PMID- 1498575 TI - Daily enzyme cleaning for giant papillary conjunctivitis. PMID- 1498576 TI - A comparison of FDG PET and IQNB SPECT in normal subjects and in patients with dementia. AB - Prior studies of patients with dementia have found similar qualitative patterns of cerebral glucose utilization with [18F]2-fluoro-2-deoxyglucose (FDG) PET and of putative muscarinic receptor activity with [123I]3-quinuclidinyl-4 iodobenzilate (IQNB). This raised doubts about whether receptor binding determines IQNB distribution and whether clinical information in IQNB scans is unique. To compare the methods directly, 4 normal volunteers and 7 patients with dementia underwent FDG PET and high-resolution IQNB SPECT scans. In normal subjects, relative regional activity from the paired scans was only weakly correlated (r = 0.29). Some regions (e.g., thalamus, frontal cortex) showed a clear disassociation of activity. In demented patients, IQNB scans tended to show larger defects than FDG scans, although one focal defect appeared only with PET. Results suggest that IQNB SPECT data are not primarily related to general physiological activity or regional cerebral blood flow and are not explained by attenuation or volume-averaging artifacts. Further studies should investigate whether IQNB scanning is a more sensitive in vivo measure of the extent of Alzheimer's disease than is FDG PET. PMID- 1498577 TI - Rapid eye movement sleep deprivation in elderly patients with concurrent symptoms of depression and dementia. AB - Rapid eye movement (REM) sleep measures distinguish elderly patients with depression from those with dementia. The authors used a 2-night REM sleep deprivation (RSD) protocol to characterize patients with mixed symptoms of depression and dementia in comparison with patients with "pure" depression or dementia and healthy controls. Mixed-symptom patients resembled dementia patients in baseline sleep measures, but their large change in phasic REM activity following RSD suggests neurobiological similarities to depression. Mixed-symptom patients with stable cognitive impairment had greater REM sleep rebound than those with a more progressive dementing course. These results are consistent with previous neuropathological and neurochemical data. PMID- 1498578 TI - Preliminary examination of the comorbidity of anxiety and depression in Parkinson's disease. AB - Significant anxiety in combination with depression may represent a specific depressive subtype in Parkinson's disease (PD). To ascertain the prevalence of this symptom complex, we administered a self-report survey and standardized psychological tests that measure anxiety and depression to 164 PD patients and 150 age-matched healthy spouse control subjects. The reporting of depression in combination with panic/anxiety best differentiated the two populations (38% vs. 8%). Depression and anxiety were highly correlated in relationship to clinical features of PD. Our findings suggest that clinically significant levels of depression and anxiety may frequently coexist in PD. The specific neuropathology of PD may predispose to this pattern of behavioral disturbance. PMID- 1498580 TI - Spatial attention in HIV-1 infection: a preliminary report. AB - In a preliminary study, 30 nondemented human immunodeficiency virus (HIV-1) seropositive subjects without acquired immunodeficiency syndrome and 14 seronegative controls performed a reaction time measure of spatial attention. Compared with controls, seropositive asymptomatic subjects showed normal facilitation of reaction time at short cue-target intervals when attention was precued, but symptomatic subjects were impaired. However, asymptomatic subjects showed no evidence of normal inhibition of attention at the cued location at longer cue-target intervals, suggesting possible subtler spatial attentional deficits in this group. Cognitive slowing in HIV-1 infection may have an attentional component, with possible involvement of both automatic and controlled processes. PMID- 1498579 TI - Cerebral metabolic dysfunction in AIDS: findings in a sample with and without dementia. AB - Positron-emission tomography was coupled with neurological and neuropsychological evaluation to study regional cerebral activity and neurologic status in two groups. Seventeen patients with full-blown AIDS and 14 seronegative control subjects were studied using [18F]2-fluoro-2-deoxy-D-glucose in a resting state. The AIDS group had relative regional hypermetabolism in the basal ganglia and thalamus; stepwise multiple-regression analyses revealed a significant relationship for the AIDS group between temporal lobe metabolism and severity of dementia on the AIDS Dementia Complex Rating Scale. These results suggest that the basal ganglia, thalamus, and temporal lobes are differentially affected in AIDS. PMID- 1498581 TI - Auditory event-related potentials in HIV-1 infection: a study in the drug-user risk group. AB - Features of event-related potentials (ERPs) may be sensitive and clinically useful markers of central nervous system infection by the human immunodeficiency virus (HIV-1); however, this application has not been studied in the risk group of intravenous drug users. Auditory ERPs generated by an "oddball" paradigm were analyzed for 39 male drug abusers as part of a multimodal assessment. Stage of HIV-1 infection was associated with prolongations of P1, N1, and P3 components of the ERP waveform. Only patients with full acquired immunodeficiency syndrome showed statistically significant increases in waveform prolongations. Specific neuropsychological deficits were not related to waveform latency prolongations. PMID- 1498582 TI - Distribution of Alzheimer's disease-associated protein (ADAP) in 10 human brains. AB - ALZ50-based enzyme immunoassay was used to study distribution of Alzheimer's disease-associated protein (ADAP) in postmortem brain tissues of 5 Alzheimer's disease (AD) and 5 non-Alzheimer's disease (NAD) subjects. There are at least three AD-associated proteins, including A68. Levels are higher in brain regions with severe neuronal loss in AD: frontal, temporal, hippocampal cortex, and amygdala. No significant ADAP was found in the NAD samples (from 2 age-matched-1 clinically demented-and 3 younger subjects). ADAP levels in four regions of AD brains were not correlated to neuritic plaque count in corresponding regions of matching formaldehyde-fixed hemispheres. PMID- 1498583 TI - Differential effects of alprazolam and buspirone upon acquisition, retention, and retrieval processes in memory. AB - A group of 125 healthy young adults was given a memory battery 1 hour after administration of alprazolam (0.5 and 1.0 mg), buspirone (5 and 10 mg), and placebo under single-dose, double-blind conditions. On the wordlist recall battery and a 24-hour retest, alprazolam appeared to impair acquisition and retention in dosages of 1.0 mg; buspirone did not adversely affect test performance at either dosage. On the basis of a 3-stage model of memory, a neuroantomical/neurophysiological model is proposed to explain the selective effects of the benzodiazepines on memory function. PMID- 1498584 TI - Intractable seizures, compulsions, and coprolalia: a pediatric case study. AB - A 10-year-old girl with intractable complex partial seizures developed aphasia, coprolalia, and repetitive motor behaviors involving touching, sexual touching, and aggressive acts. Her symptoms subsided following surgical resection of a left anterior temporal lobe ganglioglioma and control of seizures. Possible neurobehavioral implications of the reversibility of this patient's symptoms are discussed. PMID- 1498585 TI - Combined valproate and carbamazepine treatment of bipolar disorder. PMID- 1498586 TI - Psychological treatment of adult psychiatric patients with traumatic frontal lobe injury. PMID- 1498587 TI - Balancing risks and benefits: another approach to optimizing diagnostic tests. AB - In our last two articles, we showed that one can quantify the reduction in uncertainty that results from diagnostic testing, an insight that allowed us to describe a method for optimizing the performance of a test by choosing a cutoff that maximizes its information yield. Although minimizing uncertainty is an important feature of diagnostic testing, there are many situations in which diagnostic tests are most appropriately used to balance risks and benefits associated with the various possible courses of action available to a clinician. This article shows how tests can be used to maximize the "expected utility" associated with a clinical decision. PMID- 1498588 TI - Psychogenic movement disorder (pseudo-tics) in a patient with Tourette's syndrome. PMID- 1498589 TI - Trazodone treatment of targeted aggression in a mentally retarded man. PMID- 1498590 TI - Cognitive impairment in Wilson's disease. PMID- 1498591 TI - HIV-1 infection and cognitive impairment in minority groups. PMID- 1498592 TI - Capgras' syndrome of self. PMID- 1498593 TI - Capgras' syndrome and psychosis in a patient with tuberous sclerosis. PMID- 1498594 TI - The cucumber long hypocotyl mutant lacks a light-stable PHYB-like phytochrome. AB - A novel cDNA sequence homologous to a phytochrome B (phyB) gene that was isolated in a library from tobacco tissue has been used in an Escherichia coli expression system to raise anti-phytochrome B (anti-PHYB) polypeptide-specific monoclonal antibodies. The specificity of these antibodies has been tested by cross reactivity against purified pea light-labile type 1 and light-stable type 2 phytochromes, with some antibodies reacting with the type 2 and none with the type 1 phytochromes. One such antibody, monoclonal mAT1, has been employed to analyze the phytochrome molecular species present in a photomorphogenic long hypocotyl (lh) mutant of cucumber. The results indicated that the mutant contains wild-type levels of the light-labile type 1 phytochrome polypeptide (PHYA), which has an apparent molecular mass of approximately 120 kD, but shows less than 1% (detection limit) of a light-stable polypeptide recognized by mAT1 in wild-type seedlings. This protein, not detectable in the lh mutant, has the properties of light-stable type 2 phytochrome, has an apparent molecular mass of 116 to 117 kD, and remains at constant levels under continuous low-fluence-rate red light. Therefore, we conclude that the lh mutant lacks at least one type 2 phytochrome like polypeptide, most probably a phyB gene product. The correlation between the lack of this protein and the deficiency or absence of physiological responses to a light-stable phytochrome species in this mutant helps to identify the physiological roles played by the products of different subfamilies within the phytochrome gene family. PMID- 1498595 TI - Antisense inhibition of flavonoid biosynthesis in petunia anthers results in male sterility. AB - Inhibition of flower pigmentation in transgenic petunia plants was previously accomplished by expressing an antisense chalcone synthase (chs) gene under the control of the cauliflower mosaic virus (CaMV) 35S promoter. This chimeric gene was not effective in inhibiting pigmentation in anthers, presumably because the viral CaMV 35S promoter was insufficiently expressed in cell types of this organ in which the pigments are produced. Insertion of the anther box, a homologous sequence found in other genes expressed in anthers, resulted in a modified expression pattern driven by this promoter, as monitored by the beta glucuronidase (gus) gene. In addition to the basic CaMV 35S expression pattern in anthers, GUS activity was observed in tapetum cells when the modified promoter was fused to the gus gene. This promoter construct was subsequently used to drive an antisense chs gene in transgenic petunia, which led to the inhibition of pigment synthesis in anthers of five of 35 transformants. Transgenic plants with white anthers were male sterile due to an arrest in male gametophyte development. This finding indicated that flavonoids play an essential role in male gametophyte development. PMID- 1498596 TI - cis-element combinations determine phenylalanine ammonia-lyase gene tissue specific expression patterns. AB - The bean phenylalanine ammonia-lyase gene 2 (PAL2) is expressed in the early stages of vascular development at the inception of xylem differentiation, associated with the synthesis of lignin precursors. This is part of a complex program of developmental expression regulating the synthesis of functionally diverse phenylpropanoid natural products. Analysis of the expression of PAL2 promoter-beta-glucuronidase gene fusions in transgenic tobacco plants showed that functionally redundant cis elements located between nucleotides -289 and -74 relative to the transcription start site were essential for xylem expression, but were not involved in expression in leaf primordia and stem nodes or in establishing tissue specificity in petals. The -135 to -119 region implicated in xylem expression contains a negative element that suppresses the activity of a cryptic cis element for phloem expression located between -480 and -289. The functional properties of each vascular element are conserved in stem, petiole, and root, even though the xylem and phloem are organized in different patterns in these organs. We conclude that the PAL2 promoter has a modular organization and that tissue-specific expression in the vascular system involves a negative combinatorial interaction, modulation of which may provide a flexible mechanism for modification of tissue specificity. PMID- 1498597 TI - Mutations in the D1 subunit of photosystem II distinguish between quinone and herbicide binding sites. AB - The structure-activity relationships of the plastoquinone QB binding domain in the D1 subunit of photosystem II (PSII) were investigated by characterization of mutations introduced in the D1 protein. Eight novel point mutations in the gene psbA, which encodes D1, were generated in the cyanobacterium Synechocystis PCC6803 by site-specific mutagenesis in vitro. The effects of the resulting modifications in D1 on electron transfer in PSII and on herbicide binding were analyzed. The results extend the structural analogies between the secondary quinone binding site in D1 and in subunit L of the photosynthetic reaction center in purple bacteria. The involvement of Phe255, Ser264, and Leu271 of D1 in plastoquinone binding and electron transfer in PSII was established. An indirect effect of Tyr254 on the binding of QB was demonstrated. Changes in binding of herbicides and QB to D1 as a result of the mutations revealed specific interactions between amino acid residues in D1 and the plastoquinone and distinguished between the binding sites of QB and herbicides. PMID- 1498598 TI - Proaleurain vacuolar targeting is mediated by short contiguous peptide interactions. AB - Targeting of soluble proteins to the plant vacuole is mediated by determinants that reside in the polypeptide. We identified the vacuolar targeting determinant of aleurain, a plant vacuolar thiol protease, by incorporating different sequences from proaleurain into the secreted thiol protease, proendoproteinase B (proEP-B), and vice versa. The targeting fates of the chimeric proteins were analyzed by transient expression in electroporated tobacco protoplasts. The targeting determinant SSSSFADSNPIR is positioned at the N terminus of the aleurain propeptide, and its substitution into the propeptide of EP-B caused vacuolar targeting of the resulting chimeric protein. This determinant can be divided into two smaller determinants, SSSSFADS and SNPIR, each of which is sufficient to target proEP-B chimeras to the vacuole, but with lower efficiency. These smaller determinants interact in a positive manner because the combined determinant SSSSFADSNPIR targeted proEP-B with an efficiency greater than each of the smaller determinants alone. Accordingly, the efficiency of aleurain targeting was decreased when either of the smaller determinants was disrupted by replacement with similarly positioned proEP-B sequences. Further experiments on proaleurain identified an additional determinant, VTDRAAST, adjacent to the SSSSFADSNPIR determinant that is also necessary for efficient vacuolar targeting. Our results provide evidence that efficient vacuolar targeting of this thiol protease in plant cells is mediated by the combined action of smaller contiguous determinants; two of these alone are sufficient for vacuolar targeting. PMID- 1498599 TI - Both internal and external regulatory elements control expression of the pea Fed 1 gene in transgenic tobacco seedlings. AB - In previous studies using leaves of light-grown transgenic tobacco plants, we have shown that sequences located within the transcribed region of the pea Fed-1 gene (encoding ferredoxin I) are major cis-acting determinants of light-regulated mRNA accumulation. However, we show here that these internal sequences are less important for the Fed-1 light response in etiolated tobacco seedlings than they are in green leaves and that upstream elements confer organ specificity and contribute significantly to Fed-1 light responses in etiolated material. Light effects mediated by upstream response elements are thus most pronounced during the initial induction of gene activity, whereas internal elements play a more prominent role in modulating Fed-1 expression once the gene is already active. PMID- 1498600 TI - A maize embryo-specific gene encodes a proline-rich and hydrophobic protein. AB - A gene from maize that encodes a hybrid proline-rich protein (HyPRP) formed by two well-defined domains, proline-rich and hydrophobic, respectively, has been characterized at the level of its structure and expression. The proline-rich domain is composed of elements PPYV and PPTPRPS, similar to those found in PRP proteins from soybean. The hydrophobic domain is rich in cysteine and is similar to seed proteins, mainly to a soybean hydrophobic seed protein. In maize, HyPRP is encoded by a single gene, and its mRNA accumulates in immature maize zygotic embryos, with a maximum accumulation between 12 and 18 days after pollination. The HyPRP mRNA can also be detected in ovary prior to pollination. In situ hybridization experiments on embryo sections show an expression of the gene in scutellum and in nonvascular cells from the embryo axis. Functional hypotheses related to HyPRP are discussed. PMID- 1498601 TI - A carrot somatic embryo mutant is rescued by chitinase. AB - At the nonpermissive temperature, somatic embryogenesis of the temperature sensitive (ts) carrot cell mutant ts11 does not proceed beyond the globular stage. This developmental arrest can be lifted by the addition of proteins secreted by wild-type cells to the culture medium. From this mixture of secreted proteins, a 32-kD glycoprotein, designated extracellular protein 3 (EP3), that allows completion of somatic embryo development in ts11 at the nonpermissive temperature was purified. On the basis of peptide sequences and biochemical characterization, EP3 was identified as a glycosylated acidic endochitinase. The addition of the 32-kD endochitinase to ts11 embryo cultures at the nonpermissive temperature appeared to promote the formation of a correctly formed embryo protoderm. These results imply that a glycosylated acidic endochitinase has an important function in early plant somatic embryo development. PMID- 1498602 TI - A mitochondrial DNA sequence is associated with abnormal pollen development in cytoplasmic male sterile bean plants. AB - Cytoplasmic male sterility (CMS) in common bean is associated with the presence of a 3-kb unique mitochondrial sequence designated pvs. The pvs sequence encodes at least two open reading frames (297 and 720 bp in length) with portions derived from the chloroplast genome. Fertility restoration by the nuclear restorer gene Fr results in the loss of this transcriptionally active unique region. We examined the effect of CMS (pvs present) and fertility restoration by Fr (pvs absent) on the pattern of pollen development in bean. In the CMS line, pollen aborted in the tetrad stage late in microgametogenesis. Microspores maintained cytoplasmic connections throughout pollen development, indicating aberrant or incomplete cytokinesis. Pollen-specific events associated with pollen abortion and fertility restoration imply that a gametophytic factor or event may be involved in CMS. In situ hybridization experiments suggested that significant reduction or complete loss of the mitochondrial sterility-associated sequence occurred in fertile pollen of F2 populations segregating for fertility. These observations support a model of fertility restoration by the loss of a mitochondrial DNA sequence prior to or during microsporogenesis/gametogenesis. PMID- 1498603 TI - Cytokinins and auxins control the expression of a gene in Nicotiana plumbaginifolia cells by feedback regulation. AB - Both cytokinin (N6-benzyladenine [BA]) and auxin (2,4-dichlorophenoxyacetic acid [2,4-D]) stimulate the accumulation of an mRNA, represented by the cDNA pLS216, in Nicotiana plumbaginifolia suspension culture cells. The kinetics of RNA accumulation were different for the two hormones; however, the response to both was transient, and the magnitude of the response was dose dependent. Runoff transcription experiments demonstrated that the transient appearance of the RNA could be accounted for by feedback regulation of transcription and not by the induction of an RNA degradation system. The feedback mechanism appeared to desensitize the cells to further exposure of the hormone. In particular, cells became refractory to the subsequent addition of 2,4-D after the initial RNA accumulation response subsided. A very different response was observed when the second hormone was added to cells that had been desensitized to the first hormone. Under such conditions, BA produced a heightened response in cells desensitized to 2,4-D and vice versa. These findings support a model in which cytokinin further enhances the auxin response or prevents its feedback inhibition. The hormone-induced RNA accumulation was blocked by the protein kinase inhibitor staurosporin. On the other hand, the protein phosphatase inhibitor okadaic acid stimulated expression, and, in particular, okadaic acid was able to stimulate RNA accumulation in cells desensitized to auxin. This suggests that hormone activation involves phosphorylation of critical proteins on the hormone signaling pathway, whereas feedback inhibition may involve dephosphorylation of these proteins. The sequence of pLS216 is similar to genes in other plants that are stimulated by multiple agonists such as auxins, elicitors, and heavy metals, and to the gene encoding the stringent starvation protein in Escherichia coli. It is proposed that this gene family in various plants be called multiple stimulus response (msr) genes. PMID- 1498604 TI - Characterization of a plant scaffold attachment region in a DNA fragment that normalizes transgene expression in tobacco. AB - Using a low-salt extraction procedure, we isolated nuclear scaffolds from tobacco that bind specific plant DNA fragments in vitro. One of these fragments was characterized in more detail; this characterization showed that it contains sequences with structural properties analogous to animal scaffold attachment regions (SARs). We showed that scaffold attachment is evolutionarily conserved between plants and animals, although different SARs have different binding affinities. Furthermore, we demonstrated that flanking a chimeric transgene with the characterized SAR-containing fragment reduces significantly the variation in expression in series of transformants with an active insertion, whereas a SAR fragment from the human beta-globin locus does not. Moreover, the frequency distribution patterns of transgene activities showed that most of the transformants containing the plant SAR fragment had expression levels clustered around the mean. These data suggest that the particular plant DNA fragment can insulate the reporter gene from expression-influencing effects exerted from the host chromatin. PMID- 1498605 TI - Binding sites for two novel phosphoproteins, 3AF5 and 3AF3, are required for rbcS 3A expression. AB - Previous studies of boxes II (-151 to -138) and III (-125 to -114), binding sites for the nuclear factor GT-1 within the -166 deleted promoter of the ribulose-1,5 bisphosphate carboxylase-3A (rbcS-3A) gene, suggested that GT-1 might act in concert with an additional protein to confer light-responsive rbcS-3A expression. In this work, S1 analysis of RNA isolated from transgenic tobacco plants carrying mutant rbcS-3A constructs led to the identification of two short sequences located at the 5' and 3' ends of box III that are required for expression. These two sequences serve as binding sites for two novel proteins, 3AF5 and 3AF3. Gel shift studies using tetramerized binding sites for both 3AF5 and 3AF3 showed that complexes with faster mobilities were formed using nuclear extracts prepared from dark-adapted plants compared with those from light-grown tobacco plants. Phosphatase treatment of extracts from light-grown plants resulted in the formation of complexes with faster mobility. Although the binding of 3AF3 to its target site is dependent upon phosphorylation, the binding of 3AF5 does not appear to be affected by its phosphorylation state. These results suggest that the phosphorylated forms of both 3AF5 and 3AF3 are required for -166 rbcS-3A expression but that the mechanisms differ by which phosphorylation regulates the activities of 3AF5 and 3AF3. PMID- 1498606 TI - Sequences flanking the hexameric G-box core CACGTG affect the specificity of protein binding. AB - The CACGTG G-box motif is a highly conserved DNA sequence that has been identified in the 5' upstream region of plant genes exhibiting regulation by a variety of environmental signals and physiological cues. Gel mobility shift assays using a panel of G-box oligonucleotides differing in their flanking sequences identified two types of binding activity (A and B) in a cauliflower nuclear extract. Competition gel retardation assays demonstrated that the two types of binding activity were distinct. Type A binding activity interacted with oligonucleotides designated as class I elements, whereas type B binding activity interacted strongly with class II elements and weakly with class I elements. A third class of elements, null elements, did not exhibit any detectable binding under our assay conditions. Gel retardation analysis of nonpalindromic hybrid G box oligonucleotides indicated that hybrid elements of the same class exhibited binding affinity commensurate with the affinity of the weaker element, hybrid class I/II elements exhibited only type B binding, and hybrid class I/null and class II/null elements did not show any detectable binding activity. These binding activities can be explained by the affinity of bZip G-box binding homo- or heterodimer subunits for G-box half sites. These experiments led to a set of classification rules that can predict the binding activity of all reported plant G-box motifs containing the consensus hexameric core. Tissue- and/or development specific expression of genes containing G-box motifs may be regulated by the affinity of G-box proteins for the different classes of G-box elements. PMID- 1498607 TI - Homodimeric and heterodimeric leucine zipper proteins and nuclear factors from parsley recognize diverse promoter elements with ACGT cores. AB - Four short nucleotide sequences (boxes I to IV) contribute to the light responsiveness of the parsley chalcone synthase promoter. The sequence-related boxes II and III resemble several plant, viral, and bacterial promoter elements that share ACGT core sequences and are associated with diversely regulated genes. We have analyzed the binding characteristics and protein-protein interactions of factors from nuclear extracts and of three putative leucine zipper (bZIP) transcription factors potentially involved in the regulation of this promoter. These common plant regulatory factors (CPRFs) bind specifically to boxes II and III as well as other ACGT-containing promoter elements (hex1, Em1a, and as-1), though with markedly different affinities. Intact bZIP domains are crucial for CPRF binding to DNA. Distinct ensembles of nuclear factors bind to boxes II and III, despite their sequence similarity. The parsley CPRFs bind to DNA as dimers, selectively form heterodimeric DNA binding complexes, and interact with nuclear proteins. PMID- 1498608 TI - The small genome of Arabidopsis contains at least six expressed alpha-tubulin genes. AB - The goal of our investigations is to define the genetic control of microtubule based processes in a higher plant. The available evidence suggests that we have achieved our first objective: the characterization of the complete alpha-tubulin and beta-tubulin gene families of Arabidopsis. Four additional alpha-tubulin genes (TUA2, TUA4, TUA5, and TUA6) of Arabidopsis have been cloned and sequenced to complete the analysis of the gene structure for all six alpha-tubulin genes detectable on DNA gel blots of Arabidopsis genomic DNA hybridized with alpha tubulin coding sequences. TUA1 and TUA3 were characterized earlier in our laboratory. Noncoding gene-specific hybridization probes have been constructed for all six alpha-tubulin genes and used in RNA gel blot analyses to demonstrate that all six genes are transcribed. The six genes encode four different alpha tubulin isoforms; TUA2 and TUA4 encode a single isoform, as do TUA3 and TUA5. Two dimensional protein gel immunoblot analyses have resolved at least four alpha tubulin isoforms from plant tissues, suggesting that all of the predicted TUA gene products are synthesized in vivo. PMID- 1498609 TI - The small genome of Arabidopsis contains at least nine expressed beta-tubulin genes. AB - The small genome of Arabidopsis contains at least nine expressed beta-tubulin (TUB) genes, in contrast to the large genomes of vertebrate animals, which contain a maximum of seven expressed beta-tubulin genes. In this study, we report the structures of seven new TUB genes (TUB2, TUB3, TUB5, TUB6, TUB7, TUB8, and TUB9) of Arabidopsis. The sequences of TUB1 and TUB4 had been reported previously. Sequence similarities and unique structural features suggest that the nine TUB genes evolved by way of three branches in the plant beta-tubulin gene evolutionary tree. Two genes (TUB2 and TUB3) encode the same beta-tubulin isoform; thus, the nine genes predict eight different beta-tubulins. In contrast to the alpha-tubulin (TUA) genes with their divergent intron patterns, all nine TUB genes contain 2 introns at conserved positions. Noncoding 3' gene-specific hybridization probes have been constructed for all nine TUB genes and used in RNA gel blot analyses to demonstrate that all nine genes are transcribed. Two dimensional protein immunoblot analyses have resolved at least seven different beta-tubulin isoforms in Arabidopsis, indicating that most, if not all, of the TUB transcripts are translated. PMID- 1498610 TI - Preferential expression of an alpha-tubulin gene of Arabidopsis in pollen. AB - The pool of tubulin protein in tissues of Arabidopsis is provided by the expression of multiple alpha-tubulin (TUA) and beta-tubulin genes. Whereas most tubulin genes are expressed in many tissues, previous evidence suggested that the TUA1 gene might be expressed primarily in pollen. We now report a detailed analysis of TUA1 expression during Arabidopsis development. In RNA from tissues of dissected flowers, TUA1 transcripts were detected only in stamens and mature pollen. Chimeric genes containing TUA1 5' flanking DNA fused to the beta glucuronidase (GUS) coding region were used to create transgenic Arabidopsis plants. Plants containing a chimeric gene with 533 bp of 5' flanking sequence were analyzed by histochemical assay to localize GUS expression within the plant. The blue product of GUS enzyme activity accumulated very rapidly in postmitotic pollen grains. Much lower levels of GUS activity were detected in anthers with uninucleate pollen grains, in flower receptacles, and in a few vegetative tissues. Analysis of 5' deletions of the TUA1 promoter suggested that 97 bp of 5' flanking DNA is sufficient to drive GUS expression in pollen and young anthers, whereas at least 380 bp is required to detect GUS expression in the receptacle. Examination of the TUA1 promoter sequence revealed several motifs that are repeated within the TUA1 promoter and are similar to sequences in other pollen specific promoters. PMID- 1498611 TI - A geminivirus replication protein is a sequence-specific DNA binding protein. AB - The genome of the geminivirus tomato golden mosaic virus (TGMV) consists of two circular DNA molecules designated as components A and B. The A component encodes the only viral protein, AL1, that is required for viral replication. We showed that AL1 interacts specifically with TGMV A and B DNA by using an immunoprecipitation assay for AL1:DNA complex formation. In this assay, a monoclonal antibody against AL1 precipitated AL1:TGMV DNA complexes, whereas an unrelated antibody failed to precipitate the complexes. Competition assays with homologous and heterologous DNAs established the specificity of AL1:DNA binding. AL1 produced by transgenic tobacco plants and by baculovirus-infected insect cells exhibited similar DNA binding activity. The AL1 binding site maps to 52 bp on the left side of the common region, a 235-bp region that is highly conserved between the two TGMV genome components. The AL1:DNA binding site does not include the putative hairpin structure that is conserved in the common regions or the equivalent 5' intergenic regions of all geminiviruses. These studies demonstrate that a geminivirus replication protein is a sequence-specific DNA binding protein, and the studies have important implications for the role of this protein in virus replication. PMID- 1498612 TI - Internal editing of the maize chloroplast ndhA transcript restores codons for conserved amino acids. AB - The NADH dehydrogenase subunit A (ndhA) gene from maize chloroplasts encodes a highly conserved peptide, which at several positions could be restored to consensus sequences by potential C-to-U editing of the codons involved. This gene was, therefore, chosen for analysis of its mRNA sequence in the form of amplified cDNA. A comparison of this cDNA sequence with the plastome-encoded ndhA sequence reveals four C-to-U editing sites, thereby demonstrating as a novel finding that chloroplast editing can also affect internal mRNA positions. All the edited codons restore amino acids that are conserved in the ndhA-encoded peptides of other chloroplast species. Alignment with homologous mitochondrial NADH ubiquinone reductase subunit 1 (nad1) sequences of plant and even nonplant species shows that two of the editing positions restore universally conserved amino acids and that one editing site is even shared with nad1 mRNA of plant mitochondria. No editing sites could be detected in the cDNA derived from transcripts of the maize chloroplast RNA polymerase alpha-subunit (rpoA) gene. PMID- 1498614 TI - The role of the chairside assistant in laser dentistry. PMID- 1498613 TI - Mercury: it can exist undetected. PMID- 1498615 TI - The dental assistant's role in risk management informed consent. PMID- 1498616 TI - Improving the quality of life in and outside of the dental office. PMID- 1498617 TI - Nebraska dental assistant manpower and education survey. PMID- 1498618 TI - Preparing for the dental assistant certification exam. 1. PMID- 1498619 TI - Meeting OSHA requirements: document your procedures. PMID- 1498620 TI - Preparing for the dental assistant certification exam. 2. PMID- 1498621 TI - ADAA task force investigates mandatory education and credentialing. PMID- 1498622 TI - The dental assistant's role in risk management. Patient records. PMID- 1498623 TI - Dental assisting in a Guatemalan clinic. PMID- 1498624 TI - Meet the Editorial Review Board of the Dental Assistant. PMID- 1498625 TI - The dental hygienist--colleague or competitor? PMID- 1498626 TI - Ten tips for keeping good employees. PMID- 1498627 TI - Is your practice ready for a hygienist? PMID- 1498629 TI - The secret of success? Never treat a stranger. PMID- 1498628 TI - Is the time right to re-locate? PMID- 1498631 TI - Practice manager plots a profitable path. PMID- 1498630 TI - Continuing education--should it be mandatory? PMID- 1498632 TI - Aesthetic dentistry. PMID- 1498633 TI - Tobacco and oral health. PMID- 1498634 TI - IDP--the International Development Programme. PMID- 1498635 TI - Trends in cataract surgery. PMID- 1498636 TI - Future directions for brain, behavior, and the immune system. PMID- 1498637 TI - Endorectal sonography for rectal carcinoma. PMID- 1498638 TI - Widespread erosive disease with probable nasopharyngeal primary in a prehistoric Great Basin skeleton. PMID- 1498639 TI - Linguistic diversity in six cityblocks of Manhattan, with map. PMID- 1498640 TI - Hypocalcaemia: new solutions for old bottlenecks? PMID- 1498641 TI - Brainstem auditory evoked potentials in veterinary medicine. PMID- 1498642 TI - The effects of hypocalcaemia due to a 4-hour infusion of Na2EDTA solution on various blood and urine analytes in dairy cows and a comparison of these effects between cows with high and low erythrocyte potassium concentrations. AB - Six HK (high erythrocyte potassium) and 7 LK (low erythrocyte potassium) dairy cows were subjected to a 4-h intravenous infusion of 4.7% Na2EDTA solution to induce and maintain hypocalcaemia. Blood samples taken immediately before infusion, hourly for 7 h, and at 24 h after commencement of infusion were subjected to determination of concentration (or count) of 16 analytes. The mean changes in concentrations (or counts) of the various blood analytes were calculated for the periods 0-4, 4-7, 7-24, and 0-24 h after commencement of the infusion for all cows combined, and then separately for the HK and LK groups of cows. Plasma Ca(PCa), plasma inorganic phosphorus (PiP) and plasma potassium (PK) showed significant decreases during the 4-h infusion period and were still below pretreatment levels 24 h later. AST, CPK, PCVs and white cell-counts (WCCs) showed significant early increases which were still significantly elevated 24 h later. Plasma magnesium (PMg) and erythrocyte Na(ENa) and K(EK) all showed delayed changes which still persisted 24 h later. Significant between-group differences were present for PCVs which increased significantly more in the LK than the HK group during the infusion period, for PCa which showed a greater increase in the HK cows than the LK cows during the 4-7 h early clinical recovery period, and for plasma bilirubin (PBil) which showed a greater increase from 0 to 24 h in the HK group than in the LK group. Urine samples, collected before infusion, 4-7 h and 24 h after commencement of the infusion, were subjected to analysis for glucose, protein, pH, 'blood' and ketones. Most cows showed increases in urinary glucose, protein and 'blood'. PMID- 1498643 TI - Investigation of some pathophysiological effects of prolonged hypocalcaemia in sheep induced by infusing Na2EDTA solution for 4 hours daily on three consecutive days. AB - Hypocalcaemia was induced in a group of five aged Merino ewes (with low erythrocyte potassium status) by the intravenous infusion of 4.7% Na2EDTA solution for 4 h daily on 3 consecutive days. A similar control group was infused with 5.0% dextrose solution (10 ml/h) for the same period. Blood samples were taken immediately before infusion each day, hourly for 7 h, then at 08:00 each morning for a further 5 d. Studies were made on the changes in plasma (P) Ca, PNa, PK, PMg, PProtein (PProt), P inorganic phosphorus (PiP), erythrocyte (E) Na, EK, EMg, PCVs, and mean corpuscular cell volumes (MCV). Significant decreases occurred in PiP concentrations but these were only temporary, which suggests that PiP is unlikely to be involved in the complications of prolonged hypocalcaemia. Significant prolonged decreases in PNa, PK and EK and significant prolonged increases in PCVs suggested that fluid replacement therapy supplemented with Na and K may be worthy of further study in the treatment of ruminants affected by apparent biochemical or physiological complications to prolonged hypocalcaemia. PMID- 1498644 TI - Short latency auditory evoked potentials recorded from non-anaesthetized thoroughbred horses. AB - The Brainstem Auditory Evoked Potential (BAEP) is a recording of the electrical activity of the brainstem following an acoustic stimulation. Up to seven peaks may be identified within 10 ms, and are labelled I to VII. The first five of these peaks are of most clinical importance, and in normal horses, peaks I, III and V are always present at stimulus intensities of 70-100 dB. Repeated sampling of clinically normal subjects at different stimulus intensities has enabled mean latency values to be determined for the ipsilateral and contralateral peaks I, III and V, and also for the interpeak latencies (IPLs) at each intensity. The maximum, normal, absolute latency for ipsilateral peak I was 1.86 ms, for peak III, 3.53 ms and for peak V, 5.52 ms. The equivalent contralateral values were 2.50 ms, 4.44 ms and 5.59 ms. The maximum, normal, contralateral IPL for I-III was 1.78 ms, that for III-V was 2.26 ms and for I-V was 3.76 ms. The maximum, normal, contralateral IPLs were 2.17 ms for I-III, 1.41 ms for III-V and 3.32 ms for I-V. If a peak or peaks are absent or delayed, or the IPL is greater than expected, the patient can be determined to have abnormal brainstem or auditory nerve conduction. The amplitudes of peaks I and V were measured, and the ratio of amplitudes was determined, to find the normal V:I values. At a stimulus intensity of 100 dB, the ipsilateral ratio was 0.49 +/- 0.19, and the contralateral value 1.49 +/- 0.48. Dispersal values were also calculated, by dividing the height of the III-V complex by its duration. For a stimulus intensity of 100 dB, the ipsilateral dispersal value was 0.416 +/- 0.104 microV/ms, and the contralateral value of 0.473 +/- 0.074 microV/ms. A range of normal values for both V:I ratio and dispersal were calculated. Height, weight and inter-aural distance were measured, and the relationship of the various peaks and IPLs to these variables was ascertained by statistical analysis. For the ipsilateral values, the correlation between the latency of wave V, and III-V and I-V IPLs and weight were significant (P less than 0.01). Significant correlations were found between weight and the latency of contralateral waves III (P less than 0.05) and V (P less than 0.05) and the I-III (P less than 0.01) and I-V (P less than 0.001) IPLs.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1498645 TI - Changes in factor VIII activity and von Willebrand factor antigen concentration with age in dogs. AB - The factor VIII activity of 38 German shepherd puppies, 6-12 weeks old, submitted for diagnosis of haemophilia A was measured. Eight of these puppies had values higher than would be expected for haemophiliacs, but less than the reference range for adult dogs. A further sequential study of 21 puppies (6-26 weeks of age) indicated that the factor VIII activity of puppies is generally less than that of adult dogs until about 14 weeks of age. Changes in the concentration of von Willebrand factor antigen in the puppies were irregular. These variations are probably not sufficient to interfere with accurate diagnosis of haemophilia A in most affected young dogs, but may interfere with the detection of heterozygotes in young bitches. PMID- 1498646 TI - Experimental Yersinia enterocolitica placentitis in sheep. AB - A strain of Yersinia enterocolitica of O serogroup 6,30 isolated from the liver of an aborted ovine fetus was inoculated intravenously into a group of pregnant ewes at about 90 days gestation and produced placentitis with abortion or delivery of infected lambs about 50 days later. Y. enterocolitica of the same serogroup was recovered from the necrotic placental cotyledons and most other fetal tissues and could be isolated from vaginal discharges of the ewes for a least 2 weeks after abortion. Histological changes were consistent with an acute bacterial necrotizing placentitis and systemic infection of the fetus. Subsequent pregnancies in the ewes proceeded to term without evidence of infection. PMID- 1498647 TI - A preliminary study of serum haptoglobin concentration as a prognostic indicator of ovine dystocia cases. AB - Serum samples were collected prior to the correction of dystocia in 45 sheep and from nine sheep following a normal parturition. Serum samples collected from a group of 16 non-pregnant ewes acted as non-pregnant controls. The mean serum haptoglobin concentration was significantly elevated (P less than 0.01) in those dystocia cases where dead lambs were present in utero compared to those ewes which had live lambs delivered. While the number of cases presented in this study is small, there is an indication that sheep with a serum haptoglobin concentration above 1.0 g/l represent a poor surgical risk. The three ewes which died following a caesarean operation had markedly elevated serum haptoglobin concentrations prior to surgery indicating an inflammatory reaction. Five ewes with a haptoglobin concentration of 0.4 g/l made an uneventful recovery following a caesarean operation. PMID- 1498648 TI - Bilateral thalamocortical projection in hedgehogs: evolutionary implications. AB - In adult hedgehogs with large unilateral cortical deposits of fluorescent somatopetal tracers, labelled perikarya were found not only in the ipsilateral but also contralateral thalamus. An exceptionally large number of contralaterally labelled neurons was seen in the ventrolateral nucleus, also at a considerable distance from the midline. Deposits of one of two different tracers in the frontoparietal cortex of each hemisphere appear to label different perikarya in each ventrolateral nucleus. This projection to the contralateral cortex in hedgehogs does not resemble thalamo-cortical connections in either adult or developing brains of other mammalian species. Among amniotes, only in pigeons have contralateral projections from the thalamus to the telencephalon been described. The somatosensorimotor system of hedgehogs may be the only known mammalian remnant of primitive vertebrate thalamocortical organization. Whether primitive or derived, the bilateral thalamocortical projection in hedgehogs shows that hedgehog brains cannot be uncritically taken to represent brains of primate ancestors. PMID- 1498649 TI - The role of the cortex in play fighting by rats: developmental and evolutionary implications. AB - Play is a distinctive behavior of young mammals, especially mammals with a well developed forebrain. For this reason it is thought that there may be a relation between forebrain evolution and highly elaborated play behavior. This study investigated the contribution of the cortex to play behavior by comparing play in control and neonatally decorticated rats (Rattus norvegicus). Play fighting in rats involves the combination of attack by one rat and defense by the recipient, with pinning arising when specific patterns of defense are used. Whether paired with another decorticate or with an intact pairmate, decorticates attacked pairmates as frequently as did intacts, and they were just as likely to defend against playful attacks as were intacts. Where decorticates differed from intacts was on a measure of pinning, in which one rat stands over a supine partner, decorticate rats displayed a reduction of 50% relative to control rats during the juvenile stage in which play is most pronounced (days 25 to 40). Juvenile decorticate rats adopted types of defensive responses which were less likely to result in the pinning configuration. Thus, a reduced pinning frequency reflects an altered pattern of defense, not a reduced level of play fighting. Rather, the decorticate patterns of defense were typical of those defensive responses displayed by adult rats. That is, decorticate juveniles exhibit a precociously mature pattern of playful defense. As intact controls mature, they come to resemble the decorticates in their defensive responses, and hence the difference in pinning frequency between decorticate and intact pairs diminishes. This suggests that the cortex may inhibit the escalation of defense in juveniles and thus promote prolonged ventral-ventral contact during play fighting. The results further suggest that the cortex is involved in the development of adult behavioral skills by facilitating juvenile play. PMID- 1498650 TI - Discrimination of visual stimuli representing prey versus non-prey by the praying mantis Sphodromantis lineola (Burr.). AB - Adult, female praying mantids, Sphodromantis lineola (Burr.), were presented with seventy, flat black rectangles which moved toward the mantids (in the horizontal plane) against a white background. The lengths of the lures' edges parallel to their direction of movement, 1(1), were 1.5, 3, 6, 12, 18, 24, 30, 54, 72, or 114 mm; the edge lengths perpendicular to movement direction, 1(2), were 1.5, 3, 6, 12, 18, 24, or 30 mm. Mantids emitted the most predatory behaviors to square lures (1[1] = 1[2]) for which 1(1, 2) = 3-12 mm, and to 'worm' lures (1[1] greater than 1[2]) for which 1(2) = 1.5-6 mm. 'Anti-worm' lures (1[1] less than 1[2]) were poor releasers of predatory behavior. These results reconcile seemingly discrepant findings between studies that have presented mantids with various types of oscillating, rotating and/or three-dimensional lures. Further, the results indicate that like other terrestrial predators, such as toads, prey recognition by S. lineola is approximate and based on the spatiotemporal relationships between the features of moving objects (i.e. worm versus anti worm). These findings are congruent with data on mantid prey selection in the wild. PMID- 1498651 TI - Differences in optokinetic and vestibular ocular reflex performance in teleosts and their relationship to different life styles. AB - Horizontal eye movements in response to vestibular and optokinetic stimulation were investigated in 20 species of marine and fresh water teleosts. Most species performed spontaneous saccadic eye movements in light and in darkness. Successive saccades occurred either at irregular intervals and in different directions (few species), or in bursts of smaller saccades in one direction followed by saccades in the opposite direction (majority of species). Thus, in the latter group the lines of sight shifted cyclically from one side to the other about every 10-15 s. Eye movement responses in goldfish and toadfish were prototypical for two major functional groups. Optokinetic and vestibular nystagmus in the goldfish were much more regular and attained significantly higher gains than in the oyster toadfish. Optokinetic afternystagmus (OKAN) and per-/postrotatory nystagmus lasted about 10 12 s in the goldfish, but only 2-3 s in the oyster toadfish. Bilateral labyrinthectomy in goldfish resulted in optokinetic gains and OKAN durations that were very close to those of intact toadfish. These results indicate the presence (in goldfish) and the absence (in toadfish) of a functioning velocity storage network, respectively. Other non-ostariophysan teleosts failed to show a 'goldfish-like' response pattern as well. Ostariophysan species differed in their reflex performance as well. A 'goldfish-like' response pattern was observed in five of the seven cypriniform species and in two of the four characiform species but not in the four siluriform species. Positively correlated, combined response properties suggest that some species are better equipped for gaze stabilization at higher velocities than other species. These behavioral differences may parallel different specializations in locomotor pattern and mode of life. Absence of a functioning velocity storage network in bottom-dwelling teleosts (as in Amphibia) may be related to the sporadic, slow locomotion of these species and the resulting small requirements for continuous gaze stabilization during self motion at higher velocities. PMID- 1498652 TI - In vitro HRP-labeling of the fasciculus retroflexus in the lizard Gallotia galloti. AB - In order to test the usefulness of the in vitro HRP-labeling technique in the brains of small lizards, the fasciculus retroflexus was labeled in isolated brains of young specimens of the lizard Gallotia galloti by means of HRP applied with the tip of a micropipette located approximately midway along the descending course of the tract. Cells in the medial and lateral habenular nuclei were labeled retrogradely. Anterograde transport showed the course of the fasciculus retroflexus, first dorsoventrally into the paramedian prerubral tegmentum and then longitudinally into the isthmic nucleus interpeduncularis. Some fibers spread dorsally into the mesencephalic and isthmic tegmental fields. A substantial bundle continues caudally into nucleus raphe parvocellularis. Other fibers diverge rostral-wards from the point of inflexion of the fasciculus, coursing longitudinally in the medial forebrain bundle into the basal telencephalon. Some fibers course rostrally from the nucleus habenularis lateralis in the stria medullaris and could be followed to the dorsal septum. PMID- 1498653 TI - Afferent connections of the habenular complex in the lizard Gallotia galloti. AB - Afferents to the habenular complex were studied by means of in vitro horseradish peroxidase retrograde labeling and anterograde control experiments in the lizard Gallotia galloti. The medial habenular nucleus was found to receive abundant afferent fibers from the nucleus of the posterior pallial commissure and the nucleus septalis impar. More restricted input comes from the nucleus eminentiae thalami and the nucleus of the stria medullaris. The lateral habenular nucleus is innervated by various fiber groups originating from the bed nucleus of the anterior commissure, the diagonal band nucleus, the lateral preoptic area, the anterior entopeduncular nucleus, the lateral hypothalamic and mammillary areas, the nucleus of the stria medullaris, the area tegmentalis ventralis and a scattered neuronal subpopulation in the large-celled dorsolateral nucleus of the dorsal thalamus. Habenulopetal fibers generally follow the stria medullaris, but hypothalamic, entopeduncular and dorsal thalamic afferents course through the dorsal peduncle of the lateral forebrain bundle in a transthalamic route. Mesencephalic ventral tegmental afferents ascend through the tractus retroflexus. PMID- 1498654 TI - Robert L. Boord: thirty years of comparative neuroanatomy. PMID- 1498655 TI - Phylogenetic changes in the connections of the lateral preglomerular nucleus in ostariophysan teleosts: a pluralistic view of brain evolution. AB - The connections of the lateral preglomerular nucleus were examined with the fluorescent tracer DiI in a cyprinid, a characin, a catfish and a gymnotoid species. In all of these taxa the lateral preglomerular nucleus receives inputs from the torus semicircularis and projects to the telencephalon. Cytoarchitectural and topological data further support the hypothesis that the lateral preglomerular nucleus is homologous among the species examined. A cladistic analysis of species differences, however, reveals that some connections of the lateral preglomerular nucleus have changed dramatically during the course of evolution. Some of the cell groups that are interconnected with the lateral preglomerular nucleus have increased in size, while others have decreased. Increases in the number of subdivisions of cell groups are frequently associated with size increases, but they may also be associated with size decreases. Some of the connections between cell groups have increased in strength, whereas others have decreased in strength, but these connectional changes bear no simple relationship to phylogenetic changes in the size of the cell groups. Phylogenetic increases in the number of subdivisions within a cell group may be associated with selective gains of connections, but they may be associated also with selective losses of connections or with no major changes in connections. Furthermore, several cell groups and connections appear to have evolved 'de novo', whereas others have disappeared during the course of evolution. Finally, the individual cell groups within this system of interconnected nuclei have changed largely independently of one another. These findings establish that brain evolution is not dominated by a single type of phylogenetic change. PMID- 1498656 TI - Partition of function in the morphological subdivisions of the lateral geniculate nucleus of the tammar wallaby (Macropus eugenii). AB - Extra-cellular recordings from single cells in the dorsal lateral geniculate nucleus (dLGN) of the tammar wallaby, Macropus eugenii, were made to find out whether the stratification of the nucleus could be correlated with the receptive field properties of units. Retinofugal fibres terminate in the lateral geniculate nucleus of the wallaby in nine interleaved eye-specific layers. These may be grouped into a lateral alpha segment of six laminae and a medial beta segment of three, in which the cells are less densely packed. Ninety percent of the geniculate neurons recorded from in the alpha segment gave brisk responses to stimulation of their receptive fields. Cells with sluggish responses predominated in the beta segment, but there was also a sizable minority of cells with brisk responses that were indistinguishable from those recorded in the alpha segment. In contrast, other response properties were rarely differentiated in individual layers. Thus, in most layers, the numbers of cells with transient or sustained responses were not significantly different, and this was also true for cells with ON- or OFF- responses. For each of these response pairings, however, the numbers of one type (ON- and transient) predominated in every layer. The accumulation of this laminar distinction lead to significant differences in the alpha and beta segments and in the nucleus as a whole. We conclude that cells in the individual layers of the dLGN of the tammar wallaby show no evidence of having receptive field properties in common that might correlate with separate functional streams. There is a functional segregation of receptive field properties between the alpha and beta segments. The organization of these two segments resembles that of the A and the C layers of the dLGN in cats and, possibly, the magnocellular and koniocellular components of the dLGN in primates. These broad similarities in functional partition of the dLGN of different species suggests that this aspect of the organization of the nucleus is independent of lifestyle. PMID- 1498657 TI - The pattern of trunk lateral line afferents and efferents in the rainbow trout (Salmo gairdneri). AB - The primary projections of the mechanosensory posterior lateral line nerve of the rainbow trout Salmo gairdneri, a teleost without lateral line specializations, were studied by applying horseradish peroxidase (HRP). The afferents project nearly exclusively to the nucleus medialis and a small nucleus caudalis in the hindbrain, and to the eminentia granularis. In addition, there is a sparse projection to the cerebellum, but a projection to the magnocellular nucleus is lacking. The afferent projection to the lateral part of the eminentia granularis is more dense than the projection to the medial nucleus, as shown by image processing of the HRP labeling. The efferent fibers originate from a bilateral pair of large octavolateral nuclei in the hindbrain. Characteristic for these nuclei are their large, fusiform and bipolar neurons. Another specific feature is the oblique orientation of the somata, with the main dendritic shaft coursing ventrolaterally and the axonal shaft coursing dorsomedially. The axons of the efferent neurons bifurcate. The shape, orientation and size of the efferent somata are the same in the entire efferent nucleus. In contrast to other teleosts, the occurrence of efferent somata found contralaterally (21%) is substantial. The part of the octavolateral efferent nucleus innervating the neuromasts of the trunk is estimated to contain at most 150 cell bodies unilaterally. PMID- 1498658 TI - Rudolf Nieuwenhuys: twenty-five years of comparative neuroanatomy in Nijmegen. PMID- 1498659 TI - Activation of mesocortical dopaminergic system in the rat in response to neonatal medial prefrontal cortex lesions. Concurrence with functional sparing. AB - Neonatal lesions of the medial part of the rat prefrontal cortex (mPFC) (performed at the age of 6 days) resulted in a sparing in the performance of spatial delayed alternation (SDA) and an increase in dopaminergic (DA) innervation. The increased DA innervation was primarily observed in the remaining part of the mPFC. The DA fibre density was considerably higher in the non-ablated part of the mPFC, and the fibres were thicker with more large varicosities compared with sham-operated controls. Biochemical measurements showed a 3.5-fold increase in DA concentration in the remaining part of the mPFC of the animals with neonatal lesions when compared with the mPFC of sham-operated animals. In addition the DA metabolites 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) were increased. The metabolite/transmitter ratios, indicating DA utilisation, did not significantly differ from controls. The increased DA innervation and the increased concentration of DA and its metabolites in the animals with neonatal lesions further support our hypothesis that the mesocortical DA system is involved in the neural mechanism of sparing of function observed after neonatal mPFC lesions. However, sparing of function in animals with no discernable mPFC forces us to conclude that this DA response cannot be the only factor involved in the mechanism of sparing of function. PMID- 1498660 TI - Interaction of opioid peptide-containing terminals with dopaminergic perikarya in the rat hypothalamus. AB - Both direct pituitary and indirect CNS mechanisms have been postulated for the influence of opiate agonists on prolactin secretion. By examining the interactions between terminals of neurons containing opioid peptides and hypothalamic TH-positive cell bodies, this paper addressed the anatomical basis for the latter mechanism. Initial electron microscopic studies directly demonstrated contact between opioid peptide terminals and dopaminergic cell bodies and provided some visual criteria for assessing opioid-dopamine interactions at the light microscopic level. Using these guidelines, we examined the rates of contact on both A12 and A14 neurons of each of the three opioid peptide families: pro-enkephalin, pro-dynorphin, and pro-opiomelanocortin (POMC). For A14 neurons, many of which project to the posterior pituitary, contact rates were estimated at 15, 20, and 5% for dynorphin, Met-enkephalin, and ACTH (a POMC derivative), respectively. In contrast, the A12 dopamine neurons, which regulate prolactin secretion by inhibition, showed a roughly 70% contact rate with dynorphin axons (P less than 0.001) with Met-enkephalin and ACTH contact rates remaining low at 20 and 5% respectively. Contact frequency varied significantly during the estrus cycle only with dynorphin contacts on A12 neurons. Proestrus and diestrus (less so) showed a small but significant (P less than 0.05) elevation in contact rates versus estrus, male, lactating and pregnant groups. No other significant difference emerged among these groups. On the basis of these observations, we conclude that dynorphin represents a significant and specific factor in the innervation of A12 dopamine neurons. This relationship may account for some if not most of the influence of opiate agonists and antagonists on prolactin secretion. PMID- 1498661 TI - Relationship between soma diameter and oxidative enzyme activity of alpha motoneurons. AB - In order to determine whether there is a relationship between soma diameter and oxidative enzyme activity of alpha-motoneurons, we investigated the alpha motoneurons innervating the different portions within a rat gluteus medius muscle. Two fluorescent neuronal tracers, Nuclear yellow and Fast blue, were used for labeling motoneurons innervating the deep (predominance of oxidative fibers) and superficial (predominance of non-oxidative fibers) portions of the muscle. An inverse relationship between soma diameter and oxidative enzyme activity was not seen in the motoneuron pool innervating either the deep or superficial portions. When the two portions were taken together, however, the inverse relationship was seen. The inverse relationship seemed to be demonstrated in a motoneuron pool which intermingled motoneurons innervating oxidative fibers and motoneurons innervating non-oxidative fibers. These results suggest that the oxidative enzyme activity of alpha-motoneurons is not correlated strictly with their soma size. We consider that the oxidative enzyme activity of alpha-motoneurons is correlated with oxidative enzyme activity of the muscle unit. PMID- 1498662 TI - Involvement of postsynaptic G proteins in hippocampal long-term potentiation. AB - The possible involvement of postsynaptic guanosine 5-triphosphate (GTP)-binding proteins (G proteins) in long-term potentiation (LTP) was studied in rat hippocampal slices, using whole-cell recording techniques. The inclusion of guanosine 5'-O-(2-thiodiphosphate) (GDP beta S) or guanosine 5'-O-(3 thiotriphosphate) (GTP gamma S) in the recording pipette significantly reduced or abolished the baclofen-induced hyperpolarization of pyramidal neurons, which indicates uncoupling of the signal transduction from G protein-coupled receptors by these compounds. Both GDP beta S and GTP gamma S significantly attenuated the magnitude of LTP in the fimbria-CA3 synapses, but not in the mossy fiber-CA3 synapses. GTP gamma S did not attenuate LTP in the Schaffer-CA1 synapses. The effects of guanine nucleotide analogs on fimbrial LTP were reversed by postsynaptic depolarization during high frequency stimulation. These results suggest that postsynaptic G proteins may be involved in the generation of LTP in the fimbrial synapses, possibly by affecting membrane depolarization during high frequency afferent activation. PMID- 1498663 TI - Responses of hippocampal cells can be conditioned during paradoxical sleep. AB - To test the hypothesis that new associations can be acquired during sleep, we developed a conditioning paradigm in which both conditioned (CS) and unconditioned (US) stimuli were non-awakening intra-cerebral stimulations. The CS was a stimulation of the Medical Geniculate body and the US a stimulation of the Central Grey. An increase in hippocampal multiunit activity to CS was taken as the conditioned response. CS-US pairings were presented across 14 sessions, with 15 trials per session and a 24-h inter-session interval. Three groups were studied: in a group the CS-US pairings were given during the awake state (group W), and in two groups pairings were presented during sleep, either slow-wave sleep (group SWS) or paradoxical sleep (group PS). In the last group, to test the possibility of transfer to the awake state of the hippocampal response acquired in PS, the CS alone were presented interspersed with periods of wakefulness. Results showed that, before pairing, CS presentation induced no change in hippocampal multiunit activity in the three groups. After pairing, no hippocampal response to CS presentation occurred in SWS. In contrast, in the W group and in the PS group, a marked increase in hippocampal activity appeared to CS. The hippocampal response in the PS group developed progressively across sessions; it occurred only two sessions later than in the W group. Moreover, when the CS evoked response reached the asymptotic level in PS, the presentation of CS alone in awake animals elicited the hippocampal response. These results suggest that a cellular conditioning can be established during PS and that the cellular conditioned response developed in PS can be transferred to the awake state. PMID- 1498664 TI - Differential identification and localization of adenylyl cyclase and glucose transporter in brain using iodinated derivatives of forskolin. AB - Two radioiodinated derivatives of forskolin, [125I]6-IHPP-Fsk and [125I]7-IHPP Fsk, were synthesized as specific ligands for adenylyl cyclase and glucose transporter, respectively. [125I]6-IHPP-Fsk bound to bovine brain homogenates with a Kd of 9 nM and binding was inhibited by forskolin but not 1,9 dideoxyforskolin, cytochalasin B, or D-glucose. [125I]7-IHPP-Fsk bound to bovine brain homogenates at two classes of binding sites with Kd's of 56 nM and 4.7 microM; cytochalasin B and D-glucose inhibited 75% of the high affinity binding while having no effect on the low affinity binding. [125I]6-IHPP-Fsk and [125I]7 IHPP-Fsk were used to localize adenylyl cyclase and glucose transporter in rat brain by receptor autoradiography. The pattern of binding obtained with [125I]6 IHPP-Fsk was similar to that observed using [3H]forskolin to detect adenylyl cyclase. In contrast, the pattern of binding obtained with [125I]7-IHPP-Fsk was similar to that observed by others using [3H]cytochalasin B to detect glucose transporter. These iodinated ligands are selective for adenylyl cyclase and glucose transporter and require significantly shorter exposure times to yield autoradiographs than tritiated ligands. PMID- 1498665 TI - The influence of different concentrations of volatile anesthetics on the threshold for cortical spreading depression in rats. AB - We studied the influence of halothane and isoflurane on the electrical threshold for triggering spreading depression (SD) in rats. While the N-methyl-D-aspartate (NMDA) antagonist ketamine dramatically increased the triggering threshold (and blocked propagation), neither volatile agent had any dose-related effect. High doses of both agents slightly slowed SD propagation rate. These results indicate that volatile agents in typical anesthetic doses can be used in studies of SD in rats, and also suggest that these agents have little effect on NMDA receptor mediated neurotransmission. PMID- 1498666 TI - Overgrowth and pruning of dendrites in adult rats recovering from neocortical damage. AB - Unilateral lesions to the forelimb representation (FL) area of the rat sensorimotor cortex caused a time-dependent increase in the dendritic arborization of layer V pyramidal neurons in the contralateral homotopic cortex. The increase in arborization was maximum at 2-3 weeks after the lesion, following which there was a partial reduction in dendritic branching. These neural morphological changes may be related to post-lesion behavioral changes in the use of the forelimbs. PMID- 1498667 TI - An analogue of Joro spider toxin selectively suppresses hippocampal epileptic discharges induced by quisqualate. AB - The anticonvulsant effect of 1-naphthylacetyl spermine, an analogue of Joro spider toxin (JSTX), was studied against seizures induced by quisqualate (QUIS), a non-NMDA agonist, as assessed electrophysiologically and behaviorally in freely moving rats. Electrodes were implanted into right dorsal hippocampus and an injection cannula for drugs into right ventricle. The pretreatment with JSTX analogue significantly inhibited both of QUIS-induced hippocampal discharges (80 11%) and generalized tonic clonic seizures (100-33%) in a dose-dependent manner, whereas JSTX had no effect on seizures induced by quinolinate, a NMDA agonist. The paper provides the first direct evidence that the JSTX analogue exerts a potent and selective suppression of hippocampal epileptic discharges mediated by non-N-methyl-D-aspartate (non-NMDA) receptors. PMID- 1498668 TI - Antagonism of calcitonin-induced anorexia by chronic, but not acute, tricyclic antidepressants in the rat. AB - Intraperitoneal or intracerebral injections of calcitonin in the rat produce several behavioral and hormonal effects which have some analogies with the human depressive syndrome. To determine if calcitonin effects are sensitive to antidepressant drugs, the ability of antidepressants and other psychotropic drugs to interact with calcitonin-induced anorexia was tested. The results show that chronic treatments (21 days) with tricyclic, or with tetracyclic, antidepressants significantly tend to neutralize the anorectic effect of calcitonin. Other antidepressants and other psychotropic drugs had no significant effect. The acute administration (24 h) of clomipramine did not antagonize the effect of calcitonin, and even significantly enhanced it. These results allow the author to propose the effects of calcitonin in the rat as a new animal model of depression, and to raise the hypothesis that a possible mechanism of action of tricyclic antidepressant treatments is to counteract the effects of certain brain peptides. PMID- 1498669 TI - Presumptive GABAergic feedback input to the frog olfactory bulb: a double labelling study with retrograde axonal tracing and GABA immunohistochemistry. AB - The localization of gamma-aminobutyric acid (GABA)-immunoreactive neurons that project to the main olfactory bulb in the frog was studied by combining GABA immunohistochemistry with retrograde axonal tracing. Double-labelled neurons were observed in the dorsal, medial and lateral pallial areas involved in reciprocal connections with the main olfactory bulb. GABA-immunoreactive cell bodies constituted only a part of the population of bulbopetal neurons in each pallial region. This suggests that bulbopetal neurons in the frog pallium belong to neuronal populations which differ in their neurotransmitter specificities. The bulbopetal GABA-immunoreactive pallial neurons may be the source of GABAergic feedback input to the frog main olfactory bulb. PMID- 1498670 TI - Environmental modulation of behavioral tolerance in spinal rats. AB - We previously reported that the antinociceptive effect of morphine on the thermal tail withdrawal reflex (tail flick, TF) was reduced in rats that had practiced the TF response prior to morphine administration. This phenomenon, termed behavioral tolerance, was observed even when rats were spinally transected following the TF tests. The present experiments were conducted to determine whether such retention of behavioral tolerance after spinal transection was dependent on prior experience with the TF procedure, or whether other nociceptive pretreatments would also reduce opiate antinociception on the TF test in spinal rats. Separate groups of rats were pretreated with either nociceptive thermal TF or Hot Plate (HP), or mechanical Tail Pinch (TP) stimuli, as well as non nociceptive exposure to the experimental context )Habituation) or No Pretreatment. Approximately half of the rats were spinally transected after their respective pretreatment, while the other half were left intact. When Intact rats were subsequently tested on the TF at 30, 60, 120 and 180 min after morphine administration, only the TF pretreated group was tolerant, relative to the Non pretreated control group. However, this was a transient effect, and was only significant at the first, 30-min test; there was no difference among the groups in the total duration of antinociception across all the time points. When spinal rats were tested after morphine administration, there was also an overall significant difference among the groups at 30 min. In this case, the differences were maintained across all time points.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1498671 TI - Amphetamine-induced changes in behavior and caudate extracellular acetylcholine. AB - In vivo microdialysis was used to study the effects of amphetamine on caudate extracellular acetylcholine and to compare these effects to the drug-induced behavioral response profile. Consistent with an inhibitory dopamine/acetylcholine interaction, the dopamine receptor agonist, apomorphine, decreased acetylcholine concentrations, while the dopamine receptor antagonist, haloperidol, increased acetylcholine. In contrast, an intermediate dose of amphetamine (1.75 mg/kg), did not significantly alter acetylcholine levels. Furthermore, a higher dose of amphetamine (5.0 mg/kg) promoted a two-fold increase in acetylcholine levels, and the increase paralleled the appearance of oral stereotypies in these animals. These results suggest that the effects of amphetamine on caudate acetylcholine, which may be implicated in the appearance of stereotyped behaviors, are not strictly dependent on caudate dopamine receptor activation. PMID- 1498672 TI - Mechanisms of C6 glioma cell and fetal astrocyte migration into hydrated collagen I gels. AB - Fetal basal ganglia astrocytes and C6 glioma cells were plated on the surface of 1.5 cm thick hydrated collagen I wafers. Both cell types migrated through the entire thickness of the wafer within 1 day after plating. The collagen in the wafer was digested and the fine collagen I fibrils were clumped into large strands. By 2-3 days, the collagen strands were digested from the wafers and replaced by a mass of fetal astrocytes or C6 cells joined by their processes. The collagen I digestion and cell migration suggested protease production. In a second series of experiments, cultured C6 cells and E14 fetal astrocytes were immunohistochemically stained for the presence of plasminogen activators as an index of protease production. Both tissue (tPA) and urokinase (uPA) types were observed. Fetal astrocytes and C6 cells were also positive for guanidinobenzoatase, a serine protease associated with migrating cells. These data demonstrate that rapid migration of the cells on and through collagen I fibrils is concomitant with expression of plasminogen activators and proteases which can either activate or function as collagenases and release the cells from the substrate. PMID- 1498673 TI - Expression of c-fos mRNA in acute and kindled cocaine seizures in rats. AB - In situ hybridization for c-fos mRNA was performed on brain sections (a) from rats after an acute cocaine-induced seizure or from saline-injected controls and (b) from rats after their first cocaine-kindled seizure, as well as from rats that had not yet developed cocaine-kindled seizures (but were exposed to the same amount of cocaine as those that did exhibit convulsions) and from saline-injected controls. Increased expression of c-fos mRNA was observed in animals demonstrating cocaine-induced seizures acutely or following pharmacological kindling. Rats that experienced acute seizures after cocaine (65 mg/kg) showed pronounced increase in expression of c-fos mRNA in the dentate gyrus of the hippocampus and olfactory bulb. Increases were also observed in several other limbic cortical regions, as well as the striatum and ventromedial hypothalamic nucleus (VMH). In rats that were injected daily with an initially subconvulsive dose of cocaine-HCl (40 mg/kg), the cocaine-kindled seizures induced elevations in c-fos mRNA in the same brain regions as with an acute cocaine-induced seizure with the single exception of the VMH. These findings not only suggest the involvement of limbic, cortical and striatal structures in the cocaine-induced seizure, but also raise the possibility that alterations in the proto-oncogene c fos and its subsequent impact on gene expression could play a role in the changes in neural excitability associated with cocaine-induced kindling. PMID- 1498674 TI - Hypothalamic electrical activity that relates to the pulsatile release of luteinizing hormone exhibits diurnal variation in ovariectomized rats. AB - The multiunit activity (MUA) was recorded in the arcuate nucleus-median eminence region in freely moving ovariectomized rats maintained under controlled lighting conditions (lights on 05.00-19.00 h) over a period of 24 h. The MUA of each rat had been confirmed to exhibit characteristic increases (volleys) in association with pulses of luteinizing hormone. In 6 MUAs examined, the frequency of MUA volleys was significantly greater in the dark period than in the light period, suggesting a diurnal variation in the release of luteinizing hormone-releasing hormone in the ovariectomized rat. PMID- 1498675 TI - A neurofilament protein antibody selectively labels a large ganglion cell type in the human retina. AB - An antibody (SMI-32) raised against the non-phosphorylated form of the neurofilament protein triplet (NFP) revealed immunoreactivity in the soma and dendritic arborization of a group of large ganglion cells in the human retina. In addition, a population of smaller somas was also faintly labeled with this antibody in the ganglion cell layer. The completely stained cells amounted to 44,000 and were non-uniformly distributed across the retina with a peak density of 100 cells/mm2 in the retinal periphery. The soma sizes increased about two fold and dendritic field sizes about 3-fold with retinal eccentricity. The immunoreactive dendrites branched in the vitread sublamina of the inner plexiform layer. The dendritic branching pattern of these cells indicated that they correspond to the previously described shrub cells. Antibodies against NFP and neuropeptide Y showed colocalization of these markers in all of the completely stained cells. PMID- 1498676 TI - Excitatory amino acids and the actions of cocaine. AB - Antagonists of the N-methyl-D-aspartate (NMDA) type of excitatory amino acid (EAA) receptors blocked cocaine-induced stereotypy, locomotor stimulation and convulsions. These effects in general appear to involve selectively NMDA type of receptors. The results suggest that NMDA-activated systems are an integral component in the reaction sequences involved in the expression of several behavioral effects of cocaine. PMID- 1498677 TI - Activity of neurons in the rostral medulla of the halothane-anesthetized rat during withdrawal from noxious heat. AB - The physiological and pharmacological properties of two classes of putative nociceptive modulatory neurons have been extensively characterized in the rostral ventromedial medulla (RVM) of the barbiturate-anesthetized rat. 'On-cells' show a burst of activity, and 'off-cells' a sudden pause immediately preceding the occurrence of nocifensor reflexes. In the present study, we have characterized the reflex-related activity of RVM neurons in halothane-anesthetized rats to determine whether the properties of these neurons are dependent on barbiturate anesthesia. Both on- and off-cells were identified in this preparation. Repeated noxious stimulation was associated with a high level of ongoing activity in on cells, and a low level in off-cells. These data thus demonstrate that the previously described reflex-related changes in RVM neuron activity are not specific to barbiturate-anesthetized preparations, and that a failure to demonstrate off-cells in some studies may result from these neurons being inactive following repeated testing with noxious stimuli. PMID- 1498678 TI - Functional correlates of a three-component spatial model of the alpha rhythm. AB - We applied a three-component (temporal, occipital and parietal) spatial model to EEG data obtained from 46 young and 11 elderly subjects. With closed eyes the mean alpha frequency was 9.51 Hz for the temporal, 9.88 Hz for the occipital and 10.14 Hz for the parietal component. The power of the occipital component was larger than that of the others. With open eyes it was reduced to the same level as the temporal and parietal components. The power of the occipital component decreased significantly with age. PMID- 1498679 TI - Hippocampal kindling induced paired-pulse depression in the dentate gyrus and paired-pulse facilitation in CA3. AB - Rats received high frequency (100 Hz, 1 s) hippocampal stimulations that evoked afterdischarges (ADs) in a partial kindling model of epilepsy. Kindled rats were given 15 ADs over 3 days. Control rats received the same stimulation pulses at 0.17 Hz (low frequency stimulation, LFSs). Subsequent to in vivo stimulations, hippocampal slices were obtained from the rats and extracellular field responses were recorded in the CA3 cell layer following CA1 stratum radiatum stimulation, and in the granule cell layer of the dentate gyrus (DG) following perforant path stimulation. At the DG, the paired-pulse facilitation of the population spike was depressed in the kindled than the control group, on 1 day or 23 days post ADs/LFSs. The excitatory postsynaptic potential (EPSP) responses in DG following single or paired pulses were not different between kindled and control slices. At CA3, paired-pulse facilitation of both the population spike and the population EPSP was increased in the kindled compared to the control group. PMID- 1498680 TI - Identification of neuron subpopulations in the rat vestibular ganglion by calbindin-D 28K, calretinin and neurofilament proteins immunoreactivity. AB - Immunocytochemical and morphometric analyses were combined to demonstrate the presence of neuron subpopulations in the rat vestibular ganglion. Monoclonal antibodies reacting with neurofilament proteins (NF), calbindin-D 28K (CaBP) and calretinin (CaR) were used. Three subpopulations were identified: (1) CaBP- and CaR-positive neurons were the largest neurons (16%) and they were also highly NF immunoreactive; (2) exclusively NF-positive neurons; (3) unlabelled neurons, representing about two-thirds of the population. PMID- 1498681 TI - Adenosine receptor agonists inhibit the release of gamma-aminobutyric acid (GABA) from the ischemic rat cerebral cortex. AB - The effects of CPA (a selective A1 receptor agonist), NECA (a mixed A1 and A2 receptor agonist), and CGS 21680 (a selective A2 receptor agonist) on the ischemia-evoked release of gamma-aminobutyric acid (GABA) from rat cerebral cortex was investigated with the cortical cup technique. Cerebral ischemia (20 min) was elicited by four vessel occlusion. In control animals, superfusate GABA increased from a basal level of 206 +/- 26 nM (mean +/- S.E.M., n = 18) to 10,748 +/- 3,876 nM during the reperfusion period. Pretreatment with adenosine receptor agonists failed to affect basal levels of GABA release. However, CPA (10(-10) M), NECA (10(-9) M), and CGS 21680 (10(-8) M) significantly suppressed the ischemia evoked release of GABA. The ability to block the ischemia-evoked release of GABA was not evident when the adenosine receptor agonists were administered at higher concentrations. Thus, the selective activation of either A1 or high-affinity A2a adenosine receptors results in an inhibition of ischemia-evoked GABA release. PMID- 1498682 TI - Movement features and H-reflex modulation. I. Pedalling versus matched controls. AB - Modulation of soleus H-reflex magnitude over a cycle of leg movement and the adjustment of controls to account for it were explored. During pedalling, H reflex magnitudes in all nine subjects were highest in the power producing phase and lowest in recovery. Stimulation intensity was standardized. Compared to sitting, these reflexes were significantly depressed (P less than 0.05). The sitting condition was modified in one experiment, so that the angles of the limb joints and the contraction level of soleus were matched to their values, measured at 13 equi-spaced points, around the pedal cycle. This matching resulted in some modulation of the H-reflex around the pedal cycle, when sitting. When the contraction of tibialis anterior was added to these changes to the seated control, this modulation came closer to that seen during movement. Movement specific modulation of the reflex was now harder to identify. These data raise the question of whether the three features presently used for matching are causative in the movement modulation of the soleus H-reflex and whether they represent effects arising from centrally descending or peripheral sources. PMID- 1498683 TI - Movement features and H-reflex modulation. II. Passive rotation, movement velocity and single leg movement. AB - Modulation of soleus H-reflex magnitudes during pedalling, and their approximation when seated with appropriate joint positions and contractile activity was demonstrated in the previous paper. The present study investigated the modulation of H-reflexes during (A) pedalling movement in the absence of contractile activity, (B) different movement velocities and (C) movement of a single limb. Using a customized tandem cycle ergometer, seated subjects with trunk supported relaxed their leg muscles and allowed their legs to be rotated. Their feet were supported on the pedals with the ankle braced. Reflexes were collected at four phases in the movement cycle (with some at 13 phases) and with speeds of 5-60 revolutions per min (cycle times from 12 to 1 s). The results showed that (i) reflex magnitude substantially decreased with limb rotation (P less than 0.05). The degree of inhibition was dependent on the phase position. (ii) Increasing speed of passive rotation increased the inhibition at all positions, but was most pronounced near the fullest flexion of hip and knee. When subjects actively pedalled, the relationship between speed and inhibition remained. (iii) When the contralateral leg was moved and the target leg was stationary, crossed projection of reflex inhibition was clear. (iv) The reflex gain measured during active pedalling of one leg was similar to that observed during two legged pedalling. Again, a crossed effect from the contralateral leg could be observed. We conclude that the net influence of discharge from movement elicited afference is inhibitory on this reflex path and that the reflex modulation during pedalling arises from overlaid sources.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1498684 TI - Identification of an amelin isoform located in axons. AB - A new axonal isoform of amelin, an analogue of the erythrocyte spectrin binding protein termed protein 4.1 has been identified in mouse brain. This new isoform has a molecular weight of 93 kDa, and migrates to a more acidic pH (pH 7.5-8.0) than the previously described amelin E (pH 8.5) on two dimensional NEPHGE-SDS PAGE. The 93 kDa protein looks nearly identical to amelin E on two dimensional chymotryptic iodopeptide mapping, and both share partial homology with rbc protein 4.1. The new isoform is located in axons, and the soma of neurons in mouse cerebellum, while amelin E is located in neuronal soma and dendrites. The axonal amelin antibody detects a 97 kDa protein in embryonic tissue which diminishes during development; and a 93 kDa protein which is first seen at postnatal day 1 of mouse brain ontogeny, increasing constantly to its adult concentrations. This time course of expression is quite different than amelin E, which is present at embryonic day 15 and diminishes constantly reaching its lowest concentration in the adult brain. We hypothesize that axonal amelin and amelin E may play important roles in the interaction of brain spectrin(240/235) and brain spectrin(240/235E) with f-actin and neuronal membranes. PMID- 1498685 TI - A program for the application of the radial distribution function to cluster analysis in cell biology. AB - The radial distribution function g(r) is one measure of spatial pattern commonly used in statistical physics to analyze the structure of liquids and has been used in several cellular systems. The graphs of the radial distribution function present three different functional forms. The first form indicates a random distribution; in the second form the graph is characteristic of the cluster distribution; and the third type is characteristic of substantial order. The Funct-G program uses the coordinates (x,y) of each point on m photographs to calculate the radial distribution function g(r) and produce a histogram to analyze graphically this function and to define the distribution model. PMID- 1498686 TI - A profile for molecular biology databases and information resources. AB - This paper examines the requirements for building database management systems and multi-database information resources to support molecular biology research. The paper profiles the most important features of 16 integrated resources and 102 databases related to molecular biology research. The aspects surveyed in this paper include the nature of information in these databases, their sizes, update properties, cross-references, database management system heterogeneity, geographical distribution, data quality, use of temporal information and level of interpretation. The paper also comments on the access patterns to these databases. Since not all these aspects were available for all databases, specific comparisons sometimes compare fewer than the full 102 databases. Consequently, the same set of databases is not necessarily always being compared with respect to every aspect. The paper is organized primarily according to these comparison aspects and ends with some concluding remarks. PMID- 1498687 TI - A fast algorithm for counting the arrangements for packing identical items on a one-dimensional grid with application in DNA-protein and similar interactions. AB - An algorithm is described, originally developed for use with DNA-protein complexes, which precisely counts the number of possible arrangements for non overlapping items, each occupying M points, on a lattice of N such points. The algorithm counts the total number of arrangements for a given number of items and can be readily extended to count the number of arrangements which meet an additional criterion. Examples are given of two such classifications and of the application of one of them to a problem in DNA-protein interactions. PMID- 1498688 TI - PROFILEGRAPH: an interactive graphical tool for protein sequence analysis. AB - The computer program PROFILEGRAPH, a graphical interactive tool for the analysis of amino acid sequences, is described. The main task of the program is to integrate a variety of sliding-window methods into a single user-friendly shell. The program allows the user to combine any amino acid specific parameter with a selection of several possible types of analysis and to plot the resulting graph in one of several windows on the screen. It is also possible to calculate the moment of the amino acid specific parameter for a given secondary structure and to display both the absolute moment value and the moment angle relative to a reference residue. Also included are several utilities that facilitate visual analysis of protein primary structures like, for example, helical-wheel diagrams. It is possible to adapt the majority of published sliding-window analysis procedures for use with PROFILEGRAPH. PMID- 1498689 TI - Local multiple alignment by consensus matrix. AB - A new algorithm for aligning several sequences based on the calculation of a consensus matrix and the comparison of all the sequences using this consensus matrix is described. This consensus matrix contains the preference scores of each nucleotide/amino acid and gaps in every position of the alignment. Two modifications of the algorithm corresponding to the evolutionary and functional meanings of the alignment were developed. The first one solves the best-fitting problem without any penalty for end gaps and with an internal gap penalty function independent on the gap length. This algorithm should be used when comparing evolutionary-related proteins for identifying the most conservative residues. The other modification of the algorithm finds the most similar segments in the given sequences. It can be used for finding those parts of the sequences that are responsible for the same biological function. In this case the gap penalty function was chosen to be proportional to the gap length. The result of aligning amino acid sequences of neutral proteases and a compilation of 65 allosteric effectors and substrates of PEP carboxylase are presented. PMID- 1498690 TI - A knowledge base of the chemical compounds of intermediary metabolism. AB - This paper describes a publicly available knowledge base of the chemical compounds involved in intermediary metabolism. We consider the motivations for constructing a knowledge base of metabolic compounds, the methodology by which it was constructed, and the information that it currently contains. Currently the knowledge base describes 981 compounds, listing for each: synonyms for its name, a systematic name, CAS registry number, chemical formula, molecular weight, chemical structure and two-dimensional display coordinates for the structure. The Compound Knowledge Base (CompoundKB) illustrates several methodological principles that should guide the development of biological knowledge bases. I argue that biological datasets should be made available in multiple representations to increase their accessibility to end users, and I present multiple representations of the CompoundKB (knowledge base, relational data base and ASN. 1 representations). I also analyze the general characteristics of these representations to provide an understanding of their relative advantages and disadvantages. Another principle is that the error rate of biological data bases should be estimated and documented-this analysis is performed for the CompoundKB. PMID- 1498691 TI - Applications of fractal geometry to biology. AB - The applications of concepts derived from fractal geometry to biological problems are described. Three major applications are identified: modelling of structures; investigation of theoretical problems; and the measurement of complexity. The review concentrates on methods and algorithms, including potential problems, which can be used with biological problems. These algorithms are drawn from a wide range of literature, including some non-biological sources. PMID- 1498692 TI - Analysis of context of 5'-splice site sequences in mammalian mRNA precursors by subclass method. AB - The signals that direct the excision of introns from mammalian pre-mRNA are not yet well understood. However, at least three kinds of signals--5'-splice site signals, 3'-splice site signals and branch point signals--play important roles in the excision of introns. In the present paper we treat only the 5'-splice sites. In addition to a consensus sequence for 5'-splice signals, several methods have been proposed, based on a statistical model, and used to analyze relative importance of each nucleotide at each position. In our approach a nucleotide sequence is regarded as a string with symbols of 'A', 'T', 'G' and 'C'; important substrings of 5'-splice site sequences, called pattern sequences, are extracted. A pattern sequence expresses which nucleotide is needed at a limited number of positions around the 5'-splice site. It is observed that a particular pattern sequence matches predominantly 5'-splice site sequences nearest to the 5'-end of a gene and another pattern sequence matches predominantly the second nearest ones. Moreover, it is confirmed that the pattern sequences accurately predict authentic 5'-splice sites for unknown genes and explain some mutation examples. PMID- 1498693 TI - Sequence pattern matching on a massively parallel computer. AB - A method is described for finding all occurrences of a sequence pattern within a database of molecular sequences. Implementation of this on a massively parallel computer allows the user to perform very fast database searches using complex patterns. In particular, the software supports approximate pattern matching with score thresholds for either the entire pattern or specified elements thereof. Matches to individual elements can be linked by variable length gaps within user specified limits. PMID- 1498694 TI - GEOSEQ: a Pascal program to calculate statistical geometry parameters of aligned nucleic acid sequences. AB - Statistical geometry in sequence space is a statistical method used mainly to determine the topology of the divergence (i.e. tree, bundle or net) of a set of aligned sequences by combining horizontal and vertical positional information. GEOSEQ is a documented program written in Pascal that calculates the statistical geometry parameters necessary to choose between phylogenetic topologies. The input file is an optimal alignment of nucleic acid sequences in PHYLIP format (v. 3.3) with a first line containing information regarding sequences as well as some options. In order to check the randomization level associated with the obtained topology, the program has been implemented with a random generator of sequences under specified set conditions. PMID- 1498695 TI - Base-pair probability profiles of RNA secondary structures. AB - Dynamic programming algorithms are able to predict optimal and suboptimal secondary structures of RNA. These suboptimal or alternative secondary structures are important for the biological function of RNA. The distribution of secondary structures present in solution is governed by the thermodynamic equilibrium between the different structures. An algorithm is presented which approximates the total partition function by a Boltzmann-weighted summation of optimal and suboptimal secondary structures at several temperatures. A clear representation of the equilibrium distribution of secondary structures is derived from a two dimensional bonding matrix with base-pairing probability as the third dimension. The temperature dependence of the equilibrium distribution gives the denaturation behavior of the nucleic acid, which may be compared to experimental optical denaturation curves after correction for the hypochromicities of the different base-pairs. Similarly, temperature-induced mobility changes detected in temperature-gradient gel electrophoresis of nucleic acids may be interpreted on the basis of the temperature dependence of the equilibrium distribution. Results are illustrated for natural circular and synthetic linear potato spindle tuber viroid RNA respectively, and are compared to experimental data. PMID- 1498696 TI - Comparison of variance between correlated samples. PMID- 1498697 TI - GBPARSE: a parser for the GenBank flat-file format with the new feature table format. PMID- 1498698 TI - Chull.sas: an SAS macro to construct the convex hull of one (or more) finite sets of points in a plane. PMID- 1498699 TI - Human immunodeficiency virus infection in children. AB - The incidence of Acquired Immune Deficiency Syndrome (AIDS) in the pediatric population is increasing. Estimates are that in 1993 AIDS will be among the five leading causes of death in children. AIDS progresses more rapidly in children than in adults. It also has features that are unique to children, such as recurrent bacterial infections, bronchus-associated lymphoid tissue (BALT), and basal ganglia calcification. This review is written with emphasis on aspects of AIDS unique to children. Features of AIDS that are similar in adults are not discussed. PMID- 1498700 TI - MRA review. AB - Magnetic resonance (MR) angiography is a rapidly evolving field in MR imaging, the main goal of which is a noninvasive tool for visualizing blood vessels. The acquisition of continuous images of the blood vessels, comparable to the conventional DSA images, as well as the functional evaluation of blood-flow velocities and flow patterns are the subject of continuing developments. The basic principles of the various techniques and their clinical applications are reviewed and the practical limitations in specific anatomic regions discussed. The review concludes with a survey of future developments. PMID- 1498701 TI - Ossified soft tissue recurrence of giant cell tumor of bone. AB - We report 3 cases of soft tissue recurrence of giant cell tumor of bone. A peripheral rim of ossification in the soft tissue mass is pathognomonic of recurrence in the patients after resection of giant cell tumor. PMID- 1498702 TI - Inferior mesenteric artery branch avulsion from blunt trauma--CT findings. Case report. AB - Mesenteric arterial injuries are uncommon following blunt abdominal trauma. We describe the computed tomography (CT) findings of a patient with avulsion of a branch of the inferior mesenteric artery following a low-speed motor vehicle accident. PMID- 1498703 TI - Giant pseudoaneurysm of the hepatic artery--CT demonstration. Case report. AB - Noninvasive imaging studies, particularly computed tomography (CT), are the first step in evaluation of patients with suspected hepatic trauma. Iatrogenic injury, accounting for up to one-third of cases, may commonly result in hepatic artery pseudoaneurysm formation. We present a case in which a giant hepatic artery pseudoaneurysm was misinterpreted as an intrahepatic hematoma on sequential CT scans due to the failure to employ dynamic contrast-enhanced scan techniques. PMID- 1498704 TI - Hemopericardium leading to cardiac tamponade in the traumatized pediatric patient: discovery by CT. PMID- 1498705 TI - Inflammatory breast cancer: CT evaluation. AB - Eleven patients with inflammatory breast carcinoma were examined by computed tomography (CT) prior to treatment with radiation and chemotherapy. Determination was made of skin thickening of the affected breast, presence of diffuse breast tumor infiltration or mass, calcification, adenopathy; and metastases. All affected breasts demonstrated increased skin thickness relative to the nonaffected breast, ranging from 0.7 cm-3 cm. Each could further be characterized as having diffuse infiltration of the breast tissue (5), a focal mass lesion (4), or a combination of mass with associated infiltration (2). Two of the breast masses showed diffuse calcification. Only one patient had disease confined to breast tissue at the time of study. Nine patients presented with adenopathy; 7 axillary, 3 internal mammary, 2 supraclavicular, and 1 hilar. Bilateral adenopathy was noted in two patients. Distant metastases to lung, bone, or stomach were observed in 7 of 11 patients. Distant metastases and degree of adenopathy was not related to skin thickness, degree of tumor infiltration, or presence of a defined mass. Inflammatory breast cancer presents with a spectrum of computed tomography appearances. Computed tomography aids in the assessment of local disease, adenopathy, and distant metastases. PMID- 1498706 TI - Inspissated bile within the common bile duct simulating cholangiocarcinoma. Case report. AB - There are a variety of abnormalities that can lead to obstruction of the common bile duct, several of which also can cause dilatation and duct irregularity. The differential diagnosis includes such entities as cholangiocarcinoma and carcinoma of the pancreas invading the common bile duct. We present an unusual case in which inspissated bile caused irregularity and obstruction of the common bile duct that radiographically simulated a cholangiocarcinoma. PMID- 1498707 TI - Leiomyoblastoma: varied CT appearance. AB - Leiomyoblastoma is an uncommon tumor of the stomach. Usually exogastric in site, the tumor may grow to a significant size before it becomes symptomatic. Various appearances of the tumor include cystic and solid forms as well as a combination of both. Tumor hypervascularity may be identified on computed tomography (CT). The development of calcification in this tumor is rare. Late recurrence of the tumor may occur. The differential diagnosis should include leiomyosarcoma, leiomyoma, pancreatic pseudocyst, and cystadenoma. PMID- 1498708 TI - Seminoma of the testis presenting as an ulcerating mass of the duodenum. AB - Germ cell tumors (GCT) arising in the testes secondarily involve bowel in 5% of patients (1), and such involvement is usually via extension from adjacent metastatic lymphadenopathy. While this involvement often causes obstruction and gastrointestinal bleeding, radiologic identification of bowel ulceration has not been reported. We report an unusual case of small bowel invasion and ulceration, identified on CT examination, due to adenopathy resulting from testicular carcinoma. PMID- 1498709 TI - A 27-year-old woman with gradual unilateral loss of vision of one year's duration. PMID- 1498710 TI - The 1991 Borden Award Lecture. Selected aspects of intraluminal and intracellular phases of intestinal fat absorption. AB - The recognition of chylomicrons as dietary lipid transporters dates back to more than 70 years and marks a milestone in lipoprotein history. Conventionally, three phases constitute the process of absorption of exogenous fat: intraluminal, intestinal, and delivery. The intraluminal phase includes chemical hydrolysis by lipolytic enzymes and the micellar solubilization of lipolytic products by bile acids. The intestinal phase comprises the diffusion of micelles through the unstirred water layer, passive diffusion across the microvillous membrane of the enterocyte, and the formation of lipid-carrying lipoproteins. The delivery phase involves the exocytosis of chylomicrons from the absorptive cells and their subsequent removal by lymphatic structures and the systemic circulation. The precise steps and factors involved in all phases of chylomicron synthesis are not yet known, but both experimental and clinical studies have been helpful. Of the inborn metabolic disorders, the prerequisite function of apolipoprotein (apo B) for the assembly and release of lipoprotein particles stood out. Moreover, evidence emerged that the enterocyte produces apo B-100 in addition to apo B-48. Calcium and essential fatty acid status originates as determinants for triglyceride-rich particle synthesis. Furthermore, the developmental changes and regulatory factors of lipoprotein elaboration represent excellent tools in the study of the intracellular mechanisms of lipid transport. PMID- 1498711 TI - Plasma amino acid and ammonia responses to altered dietary intakes prior to prolonged exercise in humans. AB - This study examined the effects of altered dietary intakes on amino acid and ammonia (NH3) responses prior to and during prolonged exercise in humans. Six male recreational cyclists rode to exhaustion at 75% of VO2max following 3 days on a low carbohydrate (LC), mixed (M), or high carbohydrate (HC) diet in a latin square design. There were differences (p less than 0.05) in exercise times among all treatments (58.8 +/- 3.7, 112.1 +/- 7.3, and 152.9 +/- 10.3 min for the LC, M, and HC treatments, respectively). The rate of increase in plasma NH3 during exercise was greater (p less than 0.05) during the LC trial. The LC trial was also characterized by higher (p less than 0.05) resting plasma concentrations of branched chain amino acids (BCAA) and a greater decrease in these amino acids during exercise (p less than 0.05), as compared with the other two treatments. Both plasma BCAA and NH3 were susceptible to dietary manipulations. These findings suggest that limited carbohydrate availability in association with increased BCAA availability results in enhanced BCAA metabolism during exercise. This is reflected in a greater rate of increase in plasma NH3 and is consistent with the hypothesis that a significant fraction of the NH3 released during a prolonged, submaximal exercise bout is from amino acid catabolism. PMID- 1498712 TI - Glycogen consumption in hypoxic rat cardiomyocytes. AB - Glycogen consumption was investigated in isolated adult rat myocytes incubated for 2 h (37 degrees C) in substrate-free, hypoxic Krebs-Henseleit bicarbonate buffer. No consumption of glycogen occurred after 1 h of incubation, and the residual glycogen after 2 h was 23% despite an 89% reduction of the initial ATP content (from 27.1 +/- 1.8 to 3.1 +/- 0.5 nmol/mg dry weight, n = 12). The residual glycogen was not due to lactate inhibition of glycolytic enzymes, since myocytes incubated in the presence of 5 mM glucose maintained high energy phosphates throughout the incubation period despite a considerable lactate accumulation (1740 +/- 43 nmol/mg dry weight in glucose-supplemented vs. 138 +/- 14 nmol/mg dry weight in substrate-free incubations, n = 12). We have previously shown that the content of cyclic AMP in myocytes is not altered in response to hypoxia, thereby excluding activation of glycogen phosphorylase a. In the present study, the fall in myocyte ATP content was not followed by a rise in AMP, possibly preventing allosteric activation of glycogen phosphorylase b. However, addition of cyanide to the hypoxic incubations increased cellular AMP (initial level 2.1 +/- 0.4 nmol/mg dry weight vs. 9.8 +/- 0.7 after 30 min, n = 12) without increasing the amount of glycogen consumed, also ruling out the lack of glycogen phosphorylase b activation in the myocytes. Therefore, the glycogen rest was probably confined to the 17% of myocytes hypercontracted at the start of incubations. PMID- 1498713 TI - Is there a seasonal variation in mucus transport and nutrient absorption in the leopard frog? AB - We postulated that as a hibernating species, frogs might have variable demands for nutrients at different seasons of the year and that this must be reflected in seasonal variations of physiologic processes related to nutrient transport and absorption. We examined the rate of mucus transport on the ciliated palate and the movement of nutrients across the intestinal lumen of leopard frogs, Rana pipiens. Mucus transport on the frog palate was strongly influenced by season, with maximal transport occurring in late June (Julian day 178, p = 0.0001; r = 0.58). This increased transport rate was associated with a summertime increase in mucus recoil (lower tangent delta) and a decrease in mucus hydration (increase in percent solids composition). Intestinal transport of leucine, lysine, and galactose did not appear to exhibit seasonal variability. These data suggest that different mechanisms may operate in determining seasonal variability in physiologic responses. PMID- 1498714 TI - Daily variations in the sensitivity of proestrous LH surge in the inhibitory effect of intraventricular injection of 5-HT or GABA in rats. AB - Intraventricular injection of 5-hydroxytryptamine (5-HT) into female rats at 11:00 h on the day of proestrus inhibited the preovulatory surge of luteinizing hormone (LH) and ovulation. A similar response was observed after the activation of the serotonergic system by stimulation of the median raphe nucleus. A diurnal rhythm of these responses was observed. In rats acclimated to a 14-h:10-h light:dark cycle the potency of 5-HT to inhibit the LH surge and ovulation was 2.06 and 2.3 times greater, respectively, when injected at 11:00 h than at 13:00 h. Also stimulation of the median raphe nucleus at 11:00 h was significantly more effective in inhibiting these parameters than stimulation at 13:00 h. Similarly, the ability of gamma-amino-butyric acid (GABA) to inhibit the preovulatory LH surge and ovulation was greater in rats injected in the morning than in the afternoon. The results of this study indicate that during proestrus the sensitivity of 5-HT and GABA to induce inhibition of preovulatory LH release and ovulation shows daily variations with maximal effect before the critical period. PMID- 1498715 TI - Dietary sodium restriction and the development of two-kidney, one-clip hypertension in young versus adult rats. AB - To determine the effects of moderate versus severe dietary sodium restriction on the development of 2-kidney, 1-clip (2K,1C) hypertension, young male Wistar rats were placed on diets containing 9, 26, or 101 (control) mumol sodium/g food. Three days later, a solid silver clip (i.d. 0.20 mm) was placed on the left renal artery and diets were continued up to 6 weeks. Adult rats received a 0.25-mm clip. In young clipped rats receiving the 101 mumol/g diet, blood pressure (BP), plasma renin activity (PRA), and BP response to captopril were increased as early as 1 week after clipping and increased further over time. Moderate sodium restriction (26 mumol sodium/g) led to only a slight delay in the development of hypertension; the levels of BP and PRA, the BP response to captopril, and the extent of cardiac hypertrophy achieved by 6 weeks were not different between the 2K, 1C rats receiving 26 or 101 mumol sodium/g. Sodium restriction to 9 mumol/g decreased rate of growth and completely prevented the rise in BP and in left ventricular weight. At 3 and 6 weeks the severely sodium-restricted rats had significantly higher PRA levels than the 2K, 1C control group. However, the BP response to captopril was attenuated relative to the other hypertensive groups. In adult rats, this level of sodium restriction had a small, but significant effect on body weight, but still prevented the increase in BP and in left ventricular weight. In conclusion, dietary sodium restriction can prevent the development of 2K,1C hypertension in both young and adult rats, but only if the restriction is severe. This effect may relate to a marked reduction in the pressor effectiveness of the renin-angiotensin system by low sodium intake per se or by associated metabolic or other changes. PMID- 1498716 TI - Developments in the study of smooth muscle research: reflections on 42 years. AB - This review of smooth muscle research in my laboratory covers over 40 years. It focuses on research on the control of myometrium, blood vessels, gastrointestinal muscle, and airway muscle and highlights the major findings and those who made them. My goal is to show how science can be rewarding both in terms of findings and in terms of the people who make them. PMID- 1498717 TI - Are gap junctions necessary for cell-to-cell coupling of smooth muscle?: An update. AB - Earlier, it was questioned whether gap junctions (GJs) were necessary for cell cell communication in smooth muscle, and GJs were not seen in some smooth muscles. We reexamined this question in the myometrium and in intestinal smooth muscle, in light of current knowledge of the presence and function of GJs. In the uterus, numerous studies show that an increase in GJ number is associated with the onset of delivery and is required for effective parturition. In all cases, this increase in GJ number and the changes in uterine contractility were correlated with increased electrical and metabolic coupling. Evidence for the much smaller, but detectable, degree of electrical coupling in the preterm uterus is explained by the small (but again detectable) number of GJs present. In the intestine, GJs are readily detected in the circular muscle layer but have not been described in the adjacent longitudinal layer. While our immunohistochemical studies failed to detect GJs in the longitudinal layer, this may not be adequate to prove their absence. Therefore, current knowledge of GJ number and function is adequate to explain cell-cell coupling in the uterus. Although it remains uncertain whether GJs are absent from the longitudinal muscle of the intestine, there is no definitive evidence that cell-cell coupling can occur by means other than GJs. PMID- 1498718 TI - Signal transduction in smooth muscle as studied by the subcellular membrane approach. AB - Many of the contractile regulatory events in smooth muscle reside in various cellular membrane components as functional membrane constituents that interact in a variably complex manner. The physiological handling of ionized calcium (Ca2+), which serves multiple roles as an extracellular signal, a second messenger, and an activator interacting directly with myofilaments to effectuate contractile responses, referred to as Ca2+ signalling processes, represents an integral part of a more complicated membrane transduction mechanism. The subcellular membrane approach toward the understanding of Ca2+ signalling as well as the transduction mechanisms involving membrane receptors, GTP binding proteins, ion channels, membrane-bound enzymes, and the production of intracellular second messengers has made a significant contribution in smooth muscle research for the past decade. This review summarizes the current state of knowledge about the multiplicity of interactions between Ca2+ and various membrane constituents in the surface membranes and sarcoplasmic reticulum, such as Ca2+ binding, Ca2+ ATPase pumps, Ca2+ channels, and Ca2+Na+ or related ion exchangers. A number of recent novel findings from this laboratory have also been discussed. First of all, the technical refinement of membrane separation and characterization, which permits better identification of neuronal membranes in highly innervated smooth muscle tissues, led to the distinction of prejunctional and postjunctional membrane receptors. Secondly, unlike the Ca(2+)-release channels labelled with [3H]inositol 1,4,5-trisphosphate, the other type of internal membrane Ca(2+) release channels labelled by [3H]ryanodine has been identified only recently in smooth muscle.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1498719 TI - The biophysics and biochemistry of smooth muscle contraction. AB - In this review the biophysics and biochemistry of smooth muscle contraction are dealt with. We describe a new model for the study of bronchial smooth muscle, which facilitates study of cellular contractile mechanisms. A new concept emerging is that study of steady-state mechanical parameters such as maximal isometric force (Po) velocity is inadequate because two types of crossbridges (normally cycling (NBR) and latch) seem to be sequentially active during smooth muscle contraction. Thus quick-release techniques are required to characterize the force-velocity properties of the two types of bridges. Pathophysiological processes that affect the muscle's shortening ability seem to affect the early NBRs only. With respect to maximal shortening capacity of the smooth muscle, the role of loading is very important. The differences between isotonic, elastic, and viscous loading are considerable. Ultimately, the time course and magnitude of loading should exactly resemble that operative in vivo. Once again, it is the characteristic of loading in the early phase of contraction that is crucial, as most of the shortening in smooth muscle occurs early in the contraction. While the maximum force developed by smooth muscle per unit cross-sectional area is the same as for striated muscle, the velocity is 50 times less. The properties of the series and parallel elastic elements of smooth muscle are described. The latter, when in compression mode, acts as an internal resistance to shortening and probably limits it. Isotonic relaxation has therefore not been studied in smooth muscle. We have developed a shortening parameter that is independent of the load on the muscle and of the initial length of the muscle's contractile element. We report the novel observation that isotonically relaxing smooth muscle reactivates itself, resulting in terminal slowing of the relaxation process. With respect to the biochemistry of smooth muscle contraction, contractile (actin isoforms, myosin heavy and light chains and their isoforms), regulatory (calmodulin-4 Ca2+, myosin light chain kinase, myosin light chain and its phosphorylation, tropomyosin, caldesmon, and calponin), and cytoskeletal (chiefly desmin and vimentin) proteins are discussed. While the kinase activates the contractile system, caldesmon and calponin modulate the activity downward. The cytoskeletal proteins desmin, vimentin, and alpha-actinin could constitute the muscle cell's internal resistor. PMID- 1498720 TI - Hypertensive structural changes in blood vessels: do endothelial cells hold the key? AB - In recent decades, the complexity of the endothelium and its major role in maintaining or altering blood vessel architecture are being revealed. In contrast, the vascular smooth muscle cell previously received the most attention. I suggest support of the hypothesis that the endothelium is the key to vascular disease. An altered endothelium in diabetes mellitus likewise is likely to be pivotal in vascular complications that develop. We have demonstrated that adherent monocytes, indicators of altered endothelium, occur in deoxycorticosterone acetate induced hypertension in male Wistar rats. The coronary artery and thoracic aorta were investigated using transmission electron microscopy. Details of hypertensive changes were revealed as well as early atherogenic pathology in the absence of dietary modifications. Scanning electron microscopy of thoracic aorta showed details of the luminal endothelial surface and adherent monocyte-macrophages in hypertensive animals. There were two cell types: numerous typical monocytes with upstream tails, and larger cells that may have been free grazing macrophages or macrophages that had returned to the circulation. Debris and amorphous material were particularly evident in vessels from hypertensive animals. Monocytes squeezed between intact endothelial plasma membranes (as seen in section), and were found as subendothelial foam cells and phagocytosing macrophages. The endothelial adherence of monocytes to the aortas from diabetic animals was significantly (p less than 0.05) elevated over that found in controls (but not different from control-hypertensive or diabetic hypertensive animals) supporting the concept of altered endothelium in diabetes. PMID- 1498721 TI - Cerebral vascular changes associated with hemorrhagic stroke in hypertension. AB - There are a number of alterations that protect the cerebrovasculature from hemorrhagic stroke development during hypertension. The upper limit of cerebral blood flow autoregulation is shifted to higher blood pressure levels; this allows a constant blood flow to be maintained during hypertension. Studies we have performed have indicated that the middle cerebral arteries (MCA) of Wistar-Kyoto stroke-prone spontaneously hypertensive rats (spSHR) lose their ability to constrict in response to elevations in transmural pressure. The decline in such function precedes stroke development and totally disappears at an age where there is a 100% mortality from stroke. Prior to stroke development, spSHR also develop uremic conditions and signs of renal failure. The induction of uremia in stroke resistant SHR (srSHR) via nephrectomy induces these animals to develop stroke. Like prestroke spSHR, prestroke uremic srSHR also have MCA with attenuated pressure-dependent myogenic function. It is hypothesized that the inability to increase vascular resistance in response to elevations in pressure might promote overperfusion of the more distal vasculature leading to cerebral hemorrhage formation. Since uremia promotes bleeding tendencies, such alterations along with the loss of cerebrovascular myogenic function could initiate or aggravate hemorrhage formation. PMID- 1498722 TI - Cultured smooth muscle approach in the study of hypertension. AB - The systemic vasculature is known to undergo marked change in both human and experimental hypertension. The in vitro study of individual cellular components from the blood vessel wall and the regulation of their intracellular biochemical processes will aid in developing an understanding of the pathogenesis of hypertension. Vascular smooth muscle cells derived from the aorta and mesenteric arteries of normotensive and hypertensive rats can be successfully maintained in culture, providing a system free of confounding variables such as blood pressure. To assist in fully understanding the pathophysiology of hypertension, this cell culture model can be used to examine interactions between receptor and ligand, the transduction of an associated signal, characterization of subsequent intracellular responses and ultimately, quantification of a physiological and functional consequence of these events, for example, proliferation. The application of in vitro techniques to hypertension research will continue to contribute new knowledge to increase our understanding of the mechanisms behind the hypertensive disease process. PMID- 1498723 TI - Airway smooth muscle contraction at birth: in vivo versus in vitro comparisons to the adult. AB - It is clear from the literature that considerable postnatal development occurs in the contractile properties of skeletal and cardiac muscle. Nevertheless, few studies have focused on developmental changes in airway smooth muscle or on the functional capabilities of airway innervation in the newborn. Conclusions about force generation, based on measurements of pulmonary mechanics during stimulation of the vagus nerves, suggest that the newborn possesses a reduced capability to narrow airway diameter relative to the adult. This reduced in vivo response is accompanied by a reduction in maximal force generating capabilities when compared on the basis of force per unit tissue cross-sectional area (stress) in vitro. However, studies of porcine airways suggest that such a finding may simply reflect a reduction in the relative amount of contractile protein (myosin heavy chain) as seen in fetal or preterm smooth muscle. Thus, comparisons based on force normalized per cross-sectional area of myosin alter conclusions from one in which fetal tracheal smooth muscle generates less maximal force than the adult, to one in which the fetal trachea has greater contractile capabilities. Interestingly, comparisons of maximal isometric force in bronchial smooth muscle between different age groups remain unaffected when myosin heavy chain normalization is applied. Finally, there appears to be an age at which maximal force is significantly greater than at any other age, independent of the amount of smooth muscle (determined morphologically), smooth muscle myosin content, or myosin isoform. Whether this enhanced in vitro response is reflected in vivo, or is counteracted by other physiological mechanisms, remains to be seen. PMID- 1498724 TI - In vivo airway reactivity: predictive value of morphological estimates of airway smooth muscle. AB - Airway responsiveness to methacholine and other bronchoconstrictors is highly variable within and among species. The aim of the experiments in this report was to evaluate the importance of the quantity of airway smooth muscle as a determinant of intra- and inter-species variability in airway responsiveness. To do this we established concentration-response curves to methacholine in a sample of normal guinea pigs as well as in rat, rabbit, and dog. After challenge we excised the lungs for the quantitation of smooth muscle by morphometry. Animals were anesthetized with pentobarbital and mechanically ventilated using a Harvard ventilator. Aerosols of methacholine were administered in progressively doubling concentrations from 0.0625 to 256 mg/mL for a period of 30 s for each concentration. The maximal response, determined from pulmonary resistance (RL), and the concentration of methacholine required to effect 50% of the maximal RL were determined. After provocation testing the lungs were removed and fixed with 10% Formalin. Midsagittal sections and parahilar sections were stained with hematoxylin-phloxine-saffron for microscopic examination of smooth muscle. The images of all airways in the sections were traced using a camera lucida side-arm attachment and digitized using commercial software. The area of the airway wall occupied by smooth muscle was determined and standardized for airway size by dividing it by the square of the epithelial basement membrane length. The variability in airway smooth muscle in the intraparenchymal airways was significantly greater between than within individual guinea pigs (n = 13). This was not true of extraparenchymal airways.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1498725 TI - In vivo loads on airway smooth muscle: the role of noncontractile airway structures. AB - The degree of airway smooth muscle contraction and shortening that occurs in vivo is modified by many factors, including those that influence the degree of muscle activation, the resting muscle length, and the loads against which the muscle contracts. Canine trachealis muscle will shorten up to 70% of starting length from optimal length in vitro but will only shorten by around 30% in vivo. This limitation of shortening may be a result of the muscle shortening against an elastic load such as could be applied by tracheal cartilage. Limitation of airway smooth muscle shortening in smaller airways may be the result of contraction against an elastic load, such as could be applied by lung parenchymal recoil. Measurement of the elastic loads applied by the tracheal cartilage to the trachealis muscle and by lung parenchymal recoil to smooth muscle of smaller airways were performed in canine preparations. In both experiments the calculated elastic loads applied by the cartilage and the parenchymal recoil explained in part the limitation of maximal active shortening and airway narrowing observed. We conclude that the elastic loads provided by surrounding structures are important in determining the degree of airway smooth muscle shortening and the resultant airway narrowing. PMID- 1498726 TI - Activation of smooth muscle in the airway wall, force production, and airway narrowing. AB - Airway narrowing depends on smooth muscle force production and muscle shortening, but the structural and geometric properties exhibited by individual generations of the bronchial tree largely determine the extent and characteristics of airway narrowing. Properties of major importance include the nature and integrity of the epithelium, the structural and mechanical properties of the airway wall, as well as airway diameter. The influence of these properties on airway narrowing measured as flow or flow resistance in large and small diameter segments of airways from pig lung is described using a novel preparation, the perfused bronchial segment. PMID- 1498727 TI - Physiological mechanisms mediating enhanced force generation during development and immune sensitization. AB - We examined the development of acetylcholinesterase (AChase) activity and tracheal smooth muscle (TSM) contraction elicited by acetylcholine (ACh) in a swine model of maturation and a dog model of allergic bronchospasm. Strips of TSM were tethered isometrically at optimal length and responses were expressed as a percentage of the maximum to KCl-substituted perfusate (% KCl). Maximal contraction (ATmax) to ACh in 2-week-old swine (168 +/- 8% KCl) was greater than in 10-week-old swine (142 +/- 2% KCl; p less than 0.02). The AChase inhibitor, physostigmine, augmented ACh-elicited ATmax in 10-week-old (27% increase; p less than 0.01) but not in 2-week-old swine (2% increase; p is NS) and caused a greater increase in sensitivity to muscarinic activation in 2 versus 10 week-old swine (p less than 0.02), thus demonstrating increased contraction of TSM in 2 versus 10-week-old swine, which results at least in part from reduced AChase activity in immature animals. In another study, TSM from ragweed-sensitized dogs demonstrated augmented efficacy to ACh-elicited contraction (180 +/- 6% KCl) compared with TSM from sham-sensitized, littermate controls (163 +/- 4% KCl; p less than 0.05). In the presence of physostigmine, ATmax was not different between ragweed-sensitized and control TSM.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1498728 TI - Effects of inflammatory mediators on canine airway neuromuscular function. AB - Inflammatory mediators can both enhance or inhibit canine airway reactivity. PGE2 and PGI2 in general are inhibitory, interfering with release of acetylcholine and with responses to bronchoconstrictors. These prostaglandins may be more effective against agonists that open voltage-dependent Ca2+ channels to induce Ca2+ influx and contraction compared with those agonists that release internal Ca2+. Other mediators are excitatory: histamine, PGD2, thromboxane A2 (TxA2), and leukotrienes (LT) C4, D4, and E4. In canine airway only histamine and TxA2 have effects in the absence of indomethacin, i.e., in the presence of the large amounts of PGE2 and PGI2 produced in vitro LTs are ineffective. Effects of TxA2 and histamine may be potentiated if the synthesis of these inhibitory PGs is inhibited. Whether histamine or TxA2 normally promote synthesis and release of PGE2 and PGI2 in a kind of homeostasis remains to be explored. It is also unclear whether pre- as well as post-junctional TxA2 receptors exist and have different pharmacological sensitivities to antagonists. LTC4 and LTD4 also constrict canine bronchi but only when PGE2 and PGI2 synthesis is blocked and, again, whether this is a result of LT-induced release of inhibitory mediators is unknown. The concept that airway responsiveness can be caused by turning off PGE2 and PGI2 production and turning on TxA2 or LT production (or unmasking their actions) needs further exploration. Our recent data suggest that such a mechanism may explain ozone induced responsiveness in dogs. PMID- 1498729 TI - Normalization of contractile parameters in canine airway smooth muscle: morphological and biochemical. AB - Asthma research has recently highlighted the importance of correctly normalizing force development for purposes of comparing stiffness properties of smooth muscle between different airways, between airways at different stages of maturity, and between airways from different animal species. This problem does not exist in striated muscle where the entire tissue consists almost entirely of muscle and where cross bridges cycle at the same rate throughout a contraction when load correlation is made. In the bronchus, cross-sectional area of true muscle may constitute only 20-30% of the total tissue cross section, and load-independent cycling rate varies fourfold during the course of a contraction because of the occurrence of normally cycling and latch bridges. These features are responsible for the difficulty in force normalization in smooth muscle. Our studies indicate that normalization with respect to true muscle cell cross-sectional area (derived by quantitative morphometry of appropriate tissue transverse sections) is the most valid. This is only so, however, when it has been proved that the actomyosin content per unit weight of the different muscle tissues is the same. PMID- 1498730 TI - Invasive node-negative breast cancer: should all patients be referred for adjuvant therapy? PMID- 1498731 TI - Vertebral burst-fracture management in Canada. PMID- 1498732 TI - Endoscopic removal of a common-bile-duct stone associated with a Ligaclip. PMID- 1498733 TI - Misdiagnosis of bilateral breast cancer. PMID- 1498734 TI - Duodenocaval fistulas. PMID- 1498735 TI - Isolated lung transplantation. AB - A clinical reality since 1981, lung transplantation is now generally accepted as a useful procedure for patients with end-stage lung disease. Early attempts at lung transplantation were marked by infection, rejection, and, in particular, bronchial dehiscence. Obliterative bronchiolitis, an airway-targeted form of chronic rejection, continues to be a problem. It is associated with all types of lung transplantation and is an important cause of late death. In the past few years advances in surgical technique, organ preservation and postoperative management have all contributed to improved survival and preservation of lung function. The shortage of suitable organ donors remains the limiting factor in clinical programs worldwide and curtails more widespread application of lung transplantation. PMID- 1498736 TI - Recent trends in the management of breast cancer. 2. Occult breast lesions: when and how to perform a biopsy for mammographic abnormalities. AB - In 1989 the Canadian Cancer Society recommended that women over 50 years of age should undergo mammography as a test for breast cancer in centres dedicated to such programs. This recommendation and others by American societies have increased the number of mammographies done for screening purposes. As a result many mammographic abnormalities are reported by radiologists, who recommend biopsy. The surgeon should review the films with the radiologist and ensure that the anomaly is real. Attention should be given to specific signs of cancer, such as spiculated lesions; however, nonspecific signs of cancer, such as microcalcifications, microlobulation and architectural distortion, should be evaluated carefully before biopsy is carried out. Stereotaxic fine-needle aspiration can decrease the number of surgical biopsies needed. The surgical biopsy should be a one-step, segmental mastectomy done for diagnosis and treatment. The specimen should be oriented, inked and x-rayed and a definitive diagnosis made on paraffin blocks. Frozen sections should not be made of microcalcifications. PMID- 1498737 TI - Recent trends in the management of breast cancer. 3. Controversies in the use of adjuvant chemotherapy, hormonotherapy and radiotherapy for breast cancer. AB - Systemic adjuvant therapy has become a regular part of the treatment for patients with potentially curable breast cancer. At the same time radiotherapy has declined in popularity as an adjunct to mastectomy and has taken on a new role in breast conservation. Although systemic therapy has improved the prognosis for breast cancer, numerous issues, such as the optimal combination and dosage of drugs, the worth of chemohormonotherapy and the appropriate sequencing of treatment, remain the subjects of continuing investigation. PMID- 1498738 TI - Recent trends in the management of breast cancer. 4. Diagnosis and management of local recurrence after breast-conservation surgery. AB - Long-term follow-up of patients in the National Surgical Adjuvant Breast Project protocol B-06 indicated that postoperative radiotherapy is effective in reducing local recurrence rates to less than 10%. Although some recurrences represent persistence of residual disease, a second type--a local manifestation of disseminated disease--presents as an extensive process involving several quadrants of the breast and extending to adjacent skin and chest wall. The first type is amenable to salvage therapy by either lumpectomy or mastectomy, depending on the clinical situation; the second type represents surgically inoperable disease and requires systemic therapy. PMID- 1498739 TI - Experience with the AS-800 artificial urinary sphincter in myelodysplastic children. AB - The authors describe their experience with an artificial urinary sphincter (model AS-800; American Medical Systems, Minnetonka, Minn.) in treating urinary incontinence in children. Twenty-eight sphincters were implanted in 27 boys between May 1986 and June 1989. All the boys had neurogenic bladders secondary to myelomeningocele or sacral agenesis. The mean age at the time of initial implantation was 14 years (range from 9 to 19 years), and the median follow-up was 12 months (range from 6 to 31 months). The sphincters were implanted initially around the bladder neck in 25 cases. Three required reimplantation around the bulbous urethra. The complication rate was 39% (11 of 28 cases). There were two cases of erosion, two cases of infection without erosion and seven cases of device-related problems. The artificial sphincter had to be removed in four cases. There were no deaths. The revision rate was 25% (7 of 28 cases). Continence was evaluated in 22 (88%) of 25 boys who had functional sphincters in place. Five boys required oxybutinin chloride to maintain continence. Ten boys required augmentation cystoplasty before (3), after (6) and combined with (1) sphincter implantation. Eight of these 10 children were able to void spontaneously and were continent. One required intermittent catheterization twice a day and another six times a day. The authors conclude from their experience that the artificial urinary sphincter (model AS-800) can establish continence in boys with neurogenic bladders. Proper selection of the ideal patient for the artificial sphincter is essential to avoid complications. PMID- 1498740 TI - Pancreatic pseudocysts: the role of percutaneous catheter drainage. AB - The case records of 69 patients who had pancreatic pseudocysts were reviewed retrospectively. All patients had abdominal pain and tenderness, 38 had nausea and vomiting, 9 had chills and fever and 5 had jaundice. Forty-eight patients had elevated body temperatures and 26 had elevated leukocyte counts. A history of alcoholism was obtained in 48 patients. Ultrasonography demonstrated 54 pseudocysts near the body of the pancreas, 8 near the tail and 7 near the head. Thirty-nine patients had internal drainage, 16 had laparotomy and external drainage and 14 had percutaneous catheter drainage. One of these 14 patients died of uncontrollable sepsis. Six of the 39 patients who had internal drainage had clinical evidence of sepsis (4 had septic complications postoperatively, and 2 died); the remaining 33 patients who had noninfected pseudocysts left hospital within 20 days of operation. However, only four of nine patients who had percutaneous drainage for noninfected pseudocysts left hospital within 20 days of the procedure. Thus, the authors recommend that infected pancreatic pseudocysts be managed by percutaneous catheter drainage and noninfected pseudocysts by internal drainage. PMID- 1498741 TI - A survey of vertebral burst-fracture management in Canada. AB - In the management of burst fractures, the role of direct surgical removal of retropulsed bony fragments encroaching upon the spinal canal (direct decompression) is controversial. A questionnaire was mailed to 65 neurosurgeons and 36 orthopedic surgeons across Canada to determine the current management of vertebral burst fractures and the willingness of these surgeons to participate in a longitudinal study of the effects of direct surgical decompression in the management of burst fractures. Sixty-nine (44 neurologic and 25 orthopedic) surgeons responded to the questionnaire. Of those who responded, 97% of the neurologic surgeons and 95% of the orthopedic surgeons stated that they used plain radiography and computed tomography in their pretreatment investigations, and at least 50% in each specialty repeated these investigations at follow-up examinations. Standard tomography, magnetic resonance imaging and myelography were used less frequently both before and after surgery. There were no significant differences between specialties in the use of tests. Neurologic status and the treating surgeon's specialty were found to significantly influence management of burst fractures. According to 56% of neurologic surgeons and 81% of orthopedic surgeons, neurologically intact patients were usually treated with stabilization only (p less than 0.05). The greater number of neurosurgeons who used direct decompression was balanced by the number of orthopedic surgeons who used indirect decompression. Patients with partial, stable neurologic injuries were usually managed by direct decompression and stabilization according to 84% of the responding neurologic surgeons and 77% of the responding orthopedic surgeons.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1498742 TI - Transaxillary endoscopic laser sympathectomy. AB - The authors describe a technique of achieving sympathetic denervation of the upper limbs in a 20-year-old woman with hyperhidrosis. A thoracoscope was inserted through a short incision in the axilla. A fibreoptic wave guide was passed through the thoracoscope to allow photocoagulation of the second thoracic sympathetic ganglion by Nd:YAG laser irradiation. The procedure was well tolerated and subsequent scar formation was unobtrusive. PMID- 1498743 TI - [Traumatic tricuspid insufficiency with a right-to-left shunt and heart luxation]. AB - Traumatic tricuspid insufficiency (TTI) with a right-to-left shunt through a patent foramen ovale associated with a cardiac herniation was identified in a 39 year-old man with severe hypoxemia. All reported cases of TTI with a right-to left shunt are reviewed, the technical aspects of repair described and the physiologic mechanisms discussed. PMID- 1498744 TI - Surgical treatment of hepatic hydatid disease. AB - The results of surgery in 38 patients with hepatic hydatid disease are described. Cystectomy was done in four patients with small peripheral cysts. For them the mean postoperative stay was 8.2 days. Partial cystectomy, introflexion and omentoplasty were performed in 28 patients with uncomplicated large cysts. The mean postoperative stay for these patients was 8.6 days. One patient in this group died of massive hemorrhage and disseminated intravascular coagulation. Exploration of the common bile duct and choledochoduodenostomy were required in three patients who had large cysts complicated by rupture into the biliary tree. This complication resulted in a mean postoperative stay of 11.5 days. Three patients who had cysts complicated by pyogenic infection were treated with tube drainage. They were discharged with their tubes in place after a mean hospital stay of 26.5 days. Hydrogen peroxide 10% was used as a scolicidal agent and was successful in preventing dissemination. All patients underwent ultrasonography 3 months after surgery, and 28 (74%) were followed up by annual examination. There was no recurrence after a mean follow-up of 2.7 years. The results suggest that surgical treatment of hepatic hydatid disease should be governed by the size, location and complications of the cyst. The combination of partial cystectomy, introflexion and omentoplasty was safe and effective therapy for patients with large hepatic cysts uncomplicated by pyogenic infection. PMID- 1498745 TI - Complications of forearm-plate removal. AB - Reconstruction of long-bone fractures with compression plates may give rise to stress shielding under the metal plate, which may be associated with late clinical problems due to insufficiency fractures around the implants. Therefore, it is common practice to remove forearm plates after fracture healing is completed. Increasing concern has been expressed recently about the complications and morbidity associated with forearm-implant removal. A retrospective review of the management of 111 forearm diaphyseal fractures at a major Canadian centre confirmed a substantial complication rate in elective forearm-plate removal. Because the true incidence of late insufficiency fracture is not well defined, elective forearm-plate removal may be contraindicated in the asymptomatic patient. PMID- 1498746 TI - Perioperative complications of splenectomy for hematologic disease. AB - A 15-year study of perioperative complications was carried out in 142 adults who underwent splenectomy for hematologic disease at the University of Alberta Hospital in order to obtain recent statistics on morbidity and mortality. The patients were grouped into four diagnostic categories: idiopathic thrombocytopenic purpura (71 patients), lymphoproliferative disorders (34 patients), myeloproliferative disorders (12 patients) and miscellaneous disorders (25 patients). Splenectomy was carried out for therapeutic reasons in 93% of patients and to establish a diagnosis in 7%. The overall complication rate was 22% (31 of 142) and the death rate was 6% (7 of 142). Infection accounted for 42% of the complications. Steroid or antibiotic therapy preoperatively did not significantly affect the infection rate. Drains, if removed within the first week, also did not affect the postoperative infection rate. Spleen size and the interaction between diagnosis and the presence of thrombocytopenia were predictors of the need for intraoperative transfusion. PMID- 1498747 TI - Pain control and more: the subcutaneous route. PMID- 1498748 TI - A modern disease. PMID- 1498749 TI - A modern disease. PMID- 1498750 TI - Standards, guidelines and clinical policies. PMID- 1498751 TI - Educating prisoners about AIDS. PMID- 1498752 TI - Malignant melanoma: girding our loins again. PMID- 1498753 TI - Decision analysis: applications and limitations. The Health Services Research Group. PMID- 1498754 TI - Guidelines for the assessment and management of chronic obstructive pulmonary disease. Canadian Thoracic Society Workshop Group. AB - Chronic obstructive pulmonary disease (COPD) is the fifth commonest cause of death in North America and is the only leading cause of death that is increasing in prevalence. Early detection and prevention through smoking cessation are essential to stem this epidemic. Once COPD is diagnosed there is a compelling rationale for vaccination against influenza and possibly pneumococcal pneumonia, although proof of efficacy is lacking. If airways obstruction is present, inhaled quaternary anticholinergic bronchodilators or inhaled beta 2 agonists or both may be of benefit, the former agents showing fewer side effects and often greater efficacy in elderly patients. Theophylline may enhance the effect or increase the duration of the bronchodilatation produced by an inhaled agent and may offer added nonbronchodilatory effects such as improved respiratory muscle endurance and ventilatory stimulation. If significant airflow obstruction persists, an objectively monitored trial of oral steroid therapy is required. Limitation of activity despite optimum medical therapy may be alleviated in selected patients by a supervised exercise rehabilitation program. If hypoxemia is present supplemental oxygen therapy will improve the patient's survival and quality of life. Additional therapies, from respiratory stimulants to lung transplantation, remain under investigation. PMID- 1498756 TI - "Stress" and lipids. PMID- 1498755 TI - Use of host factors to identify people at high risk for cutaneous malignant melanoma . AB - OBJECTIVE: To determine which host characteristics are risk factors for cutaneous malignant melanoma in order to aim prevention and early detection programs at people at high risk. DESIGN: Case-control study. SETTING: Southern Ontario. SUBJECTS: The 583 case subjects were aged 20 to 69 years and had had malignant melanoma newly diagnosed between Oct. 1, 1984, and Sept. 30, 1986. The 608 control subjects were randomly selected from a list of residents in the study area and were stratum matched for age, sex and municipality. INTERVENTION: Through in-person interviews the interviewer ascertained exposure to putative external risk factors and assessed skin colour and number of nevi on the arm, and the subject reported his or her natural hair colour at age 20 years, eye colour, skin reaction to repeated sun exposure, and freckle and whole-body nevus densities. RESULTS: Although all the host factors mentioned were significantly associated with melanoma risk when considered separately, only hair colour, skin reaction to repeated sun exposure, and self-reported freckle and nevus densities remained significant after backward logistic regression analysis. The odds ratio for melanoma was estimated to be 10.7 in people who had many nevi compared with those who had none (95% confidence interval [CI] 6.6 to 17.4), 4.0 in people who had red hair compared with those who had black hair (95% CI 1.9 to 8.2), 1.9 in people who had many freckles compared with those who had none or few (95% CI 1.3 to 2.8) and 1.4 respectively in people who burned and had a subsequent increase in tan and those who burned and had no increase in tan after repeated sun exposure compared with those who did not burn [corrected]. CONCLUSIONS: Four risk factors for malignant melanoma have been identified. Prospective evaluation of their predictive value should be done. In the meantime, however, these factors should be used to identify people apparently at high risk for malignant melanoma, who can then be targeted for early detection and prevention programs. PMID- 1498757 TI - The by-products of conception. 1968. PMID- 1498758 TI - Goodbye Ontario, hello California: leaving medicare for the Kaiser Permanente system. PMID- 1498759 TI - Canadians' access to abortion still limited, activists argue. PMID- 1498760 TI - Physician, tape thyself, communication expert advises. PMID- 1498761 TI - Family physicians use WONCA meeting to compare approaches to cholesterol screening. PMID- 1498762 TI - Innovative approaches proving attractive to growing number of entrepreneurial MDs. PMID- 1498763 TI - In Europe, they still love to light up. PMID- 1498764 TI - Controversial AIDS-transmission case sent to trial by Ontario judge. PMID- 1498766 TI - Laboratory methods for early detection of human immunodeficiency virus type 1 in newborns and infants. AB - Cumulative data on serological testing of newborns and infants have shown that (i) maternal and newborn anti-HIV-1 IgG titers are high at delivery, which may explain the persistence of antibody in the infants of seropositive mothers; (ii) in some situations, serial HIV-1 antibody testing may identify infected infants; and (iii) detection of anti-HIV-1 IgA or IgM is specific for infection but the sensitivity of this assay may be compromised in certain situations, such as when infected infants are hypogammaglobulinemic or when the rise and fall of HIV-1 specific IgM synthesis following acute infection has been completed before delivery of the infant. Cumulative data on PCR, viral culture, and tests for antigen in newborns and infants have shown that (i) among all age groups, viral culture is probably the most specific test available for detection of HIV-1, as PCR and the p24 antigen test may (though rarely) give false-positive results; (ii) the sensitivity of these tests increases in the order of antigen, culture, and PCR, with relatively insensitive results in the first 3 months of life for all of these tests; (iii) the sensitivity of all of these tests improves and approximates 90 to 100% when infants over 6 months of age are tested; and (iv) data regarding the sensitivity, specificity, and usefulness of these virological assays in infants under 3 months of age are very scant and inconclusive. PMID- 1498767 TI - Molecular and immunological diagnosis of echinococcosis. AB - Echinococcosis is an infectious disease of humans caused by the larval (metacestode) stage of the cestode species Echinococcus granulosus (cystic echinococcosis or hydatid disease) or Echinococcus multilocularis (alveolar echinococcosis or alveolar hydatid disease). Clinical manifestations depend primarily on localization and size of hepatic lesions and may include hepatomegaly, obstructive jaundice, or cholangitis. Prognostically, alveolar echinococcosis is considered similar to liver malignancies, including a lethality rate of 90% for untreated cases. Diagnosis is based on imaging techniques coupled with immunodiagnostic procedures. Antibody detection tests for E. multilocularis have markedly improved with the use of affinity-purified Em2 antigen and recombinant antigen II/3-10 in enzyme immunoassays. Antigens of corresponding quality for E. granulosus are still unavailable. The detection of circulating antigens and immune complexes in the sera of patients with cystic echinococcosis, the demonstration of in vitro lymphocyte proliferation in response to stimulation with Echinococcus antigens, and the discrimination of serum immunoglobulin isotype activity to various Echinococcus antigens in both cystic and alveolar echinococcosis have been suggested for diagnostic purposes as well as for monitoring patients after treatment. New diagnostic molecular tools include DNA probes for Southern hybridization tests and polymerase chain reaction for the amplification of E. multilocularis and E. granulosus species-specific DNA fragments. PMID- 1498765 TI - Gardnerella vaginalis: characteristics, clinical considerations, and controversies. AB - The clinical significance, Gram stain reaction, and genus affiliation of Gardnerella vaginalis have been controversial since Gardner and Dukes described the organism as the cause of "nonspecific vaginitis," a common disease of women which is now called bacterial vaginosis. The organism was named G. vaginalis when taxonomic studies showed that it was unrelated to bacteria in various genera including Haemophilus and Corynebacterium. Electron microscopy and chemical analyses have elucidated the organism's gram-variable reaction. Controversy over the etiology of bacterial vaginosis was largely resolved by (i) studies using improved media and methods for the isolation and identification of bacteria in vaginal fluids and (ii) standardization of criteria for clinical and laboratory diagnosis. Besides G. vaginalis, Mobiluncus spp., Mycoplasma hominis, and certain obligate anaerobes are now acknowledged as participants in bacterial vaginosis. The finding that G. vaginalis, Mobiluncus spp., and M. hominis inhabit the rectum indicates a potential source of autoinfection in addition to sexual transmission. Extravaginal infections with G. vaginalis are increasingly recognized, especially when the toxic anticoagulant polyanetholesulfonate is omitted from blood cultures and when urine cultures are incubated anaerobically for 48 h. The finding that mares harbor G. vaginalis suggests that an equine model can be developed for studies of Gardnerella pathogenesis. PMID- 1498768 TI - Automated systems for identification of microorganisms. AB - Automated instruments for the identification of microorganisms were introduced into clinical microbiology laboratories in the 1970s. During the past two decades, the capabilities and performance characteristics of automated identification systems have steadily progressed and improved. This article explores the development of the various automated identification systems available in the United States and reviews their performance for identification of microorganisms. Observations regarding deficiencies and suggested improvements for these systems are provided. PMID- 1498771 TI - Multiple dopamine receptors: functional implications. PMID- 1498770 TI - Listeria monocytogenes CAMP reaction. PMID- 1498772 TI - The nature and recurrence of RBD on placebo. PMID- 1498769 TI - Oral immunization using live attenuated Salmonella spp. as carriers of foreign antigens. AB - A variety of techniques, including the use of live oral vaccines, have been used to deliver antigens to the gut-associated lymphoid tissues in an attempt to initiate production of specific secretory immunoglobulin A for protection against pathogens that colonize or cross mucosal surfaces to initiate infection. A number of attenuated Salmonella mutants are able to interact with the lymphoid tissues in the Peyer's patches but are not able to cause systemic disease. Some of these mutants are effective as live vaccines (i.e., able to protect against infection with the virulent Salmonella parent) and are candidates for use as carriers for virulence determinants of other mucosal pathogens. This has been shown to be an effective means of stimulating significant levels of specific mucosal secretory immunoglobulin A directed against the carrier strains and against a variety of heterologous antigens and has been shown to stimulate production of serum antibodies and cell-mediated responses as well. This review examines the history of this mechanism of vaccine delivery and summarizes the most recent applications of this evolving technology. This is a technique for vaccine delivery with significant potential for influencing the management of infectious diseases on a large scale. It can be used not only for vaccines against enteric bacterial pathogens but also for vaccines against a variety of other bacteria, viruses, and parasites. The results obtained to date are encouraging, and there is great potential for development of safe, effective, affordable vaccines. PMID- 1498773 TI - A volumetric MRI study of limbic structures in chronic schizophrenia- relationship to psychopathology. PMID- 1498774 TI - An MRI study in schizophrenia: relationships with structural imaging, evoked potentials and neuropsychological test results. PMID- 1498775 TI - Controlled MRI studies in psychiatric patients--relations to functional imaging methods (EEG mapping, SPECT and PET). PMID- 1498776 TI - MR imaging and spectroscopy in schizophrenia in relation to the neurodevelopmental hypothesis. PMID- 1498777 TI - Cortical volume reduction in schizophrenia using MRI. PMID- 1498778 TI - Anatomical abnormalities in the brains of monozygotic twins discordant and concordant for schizophrenia. PMID- 1498780 TI - Has recurrent brief depression a different pharmacology. PMID- 1498779 TI - The ionic basis of neurocytotoxic damage. PMID- 1498781 TI - Clinical benefit of slow calcium channel antagonists in cerebral ischaemia. PMID- 1498782 TI - Potassium channels control the electrical activity of serotoninergic neurons in the dorsal raphe nucleus. PMID- 1498783 TI - Electrophysiological studies on the heterogeneity of 5-HT1A receptors: psychopharmacological implications. PMID- 1498784 TI - Differential influence of dopaminergic and noradrenergic afferents on their target cells in the rat prefrontal cortex. PMID- 1498785 TI - Muscarinic regulation of neuronal functioning in prefrontal cortex: basic mechanisms and clinical implications. PMID- 1498786 TI - Dual mechanisms of opiate dependence in the locus coeruleus. PMID- 1498787 TI - Molecular biology and pharmacology of histamine receptor subtypes. PMID- 1498788 TI - Recurrent brief depression: a DSM-IV perspective. PMID- 1498789 TI - Stress and psychopathology: an overview. PMID- 1498790 TI - Prenatal stress and the expression of stress-induced responses throughout the life span. PMID- 1498791 TI - Changes in the HPA axis associated with aging and neuropsychiatric illness. PMID- 1498792 TI - Neuroendocrine responses related to stress in children with psychopathology. PMID- 1498793 TI - Co-morbidity of depression: evidence from epidemiology. PMID- 1498794 TI - The genetics of depression and related traits. PMID- 1498795 TI - Depression in medical and surgical patients in the general hospital. PMID- 1498797 TI - The biology of panic attacks. PMID- 1498796 TI - Depressive disorders and organic brain disorders: validation of the depressive signs scale. PMID- 1498798 TI - The naturalistic course of anxiety and depressive disorders. PMID- 1498799 TI - Suicide attempts, panic disorder, and depression: an update. PMID- 1498800 TI - Comorbidity of panic disorder in a community sample. PMID- 1498801 TI - Long-term treatment: risk/benefit ratio and therapeutic outcome. PMID- 1498802 TI - The epidemiology and genetics of panic disorder. PMID- 1498803 TI - Methodological aspects of perfusion SPECT. PMID- 1498804 TI - RCBF in Alzheimer's disease: current issues. PMID- 1498805 TI - SPECT in Alzheimer's disease. PMID- 1498806 TI - Cerebral blood flow response to a mental activation task in early Alzheimer disease. PMID- 1498807 TI - Diagnostic value of HMPAO-SPECT and topographic analysis of EEG in dementia of Alzheimer type. PMID- 1498808 TI - In vivo imaging of cerebral muscarinic receptors with I-123 QNB and SPECT: studies in normal subjects and patients with dementia. PMID- 1498809 TI - Intraneuronal signalling systems as targets for the development of novel mood stabilizing drugs. PMID- 1498810 TI - Role of G proteins in signal transduction. PMID- 1498811 TI - Lithium interaction with adenylate cyclase signalling system. PMID- 1498812 TI - Effects of psychotropic drugs and releasing hormones on pituitary hormone stimulation in depressed patients. PMID- 1498814 TI - The necessity of physiologic subtyping in schizophrenia. PMID- 1498813 TI - 5-HT1A receptor sensitivity in depression and anxiety disorders: molecular mechanisms of neuroadaption. PMID- 1498816 TI - Neuroendocrine studies of the aetiology of puerperal psychosis. PMID- 1498815 TI - Confounding variables in neuroendocrine challenge tests: what we need to control for. PMID- 1498817 TI - Pharmacological challenge and PET imaging. PMID- 1498818 TI - Performing genetic analysis with irregular traits. PMID- 1498819 TI - Looking for genes in schizophrenia. PMID- 1498820 TI - Pharmacokinetics of psychotropic drugs in children. PMID- 1498821 TI - Pharmacotherapy of adolescent depression. PMID- 1498822 TI - Pharmacotherapy of childhood anxiety disorders. PMID- 1498823 TI - Monoamines in personality disorder. PMID- 1498824 TI - PET studies with L-[11C]5-HTP and L-[11C]dopa in brains of healthy volunteers and patients with major depression. PMID- 1498825 TI - An overview of variability in drug response and traditional approaches to dosage regimen design. PMID- 1498826 TI - Steady-state predictions based on first dose data. PMID- 1498827 TI - Statistical estimation of pharmacokinetic/dynamic variability. PMID- 1498828 TI - Brain laterality and individual differences in drug responses. PMID- 1498829 TI - Individual differences in addictive liability: associated behavioral and biochemical features. PMID- 1498830 TI - Genotype-dependent adaptation of mesolimbic dopamine system and stress-induced behavioral sensitization to amphetamine. PMID- 1498831 TI - Selective serotonin reuptake inhibitors in OCD. PMID- 1498833 TI - Metabolic approaches to physiologic subtyping of schizophrenia. PMID- 1498832 TI - Disorders related to OCD--neurobiology. PMID- 1498834 TI - Animal models of obsessive compulsive disorder. PMID- 1498835 TI - Headache and personality. PMID- 1498836 TI - Migraine and psychopathology: epidemiologic and genetic aspects. PMID- 1498837 TI - Migraine and depression: biological aspects. PMID- 1498838 TI - Migraine and psychiatric disorders: a prospective epidemiologic study. PMID- 1498839 TI - The epidemiology of depression in old age: the importance of physical illness. PMID- 1498840 TI - Prevalence, course and treatment of depression among residents in old age homes. PMID- 1498841 TI - Differences in structure of depression in elderly and young patients with major depression. DUAG. Danish University Antidepressant Group. PMID- 1498842 TI - Treatment of depression in the elderly. PMID- 1498843 TI - Nortriptyline: a model drug in geriatric depression. PMID- 1498844 TI - The physiologic subtyping of schizophrenia: genetic approaches. PMID- 1498845 TI - Cardiovascular and central nervous system toxicity of antidepressants. PMID- 1498846 TI - Cholinergic mechanisms in sleep and circadian rhythms. PMID- 1498847 TI - Sleep abnormalities in schizophrenia: cholinergic contribution. PMID- 1498848 TI - Serotonin and ethanol drinking in the alcohol-preferring (P) rat. PMID- 1498849 TI - Gamma-hydroxybutyric acid in the treatment of alcohol dependence. PMID- 1498850 TI - Reaction to alcohol as a predictor of alcoholism. PMID- 1498851 TI - Towards a standardisation for the methodology in treatment research of alcohol abuse and alcoholism. PMID- 1498852 TI - Aging of brain cholinergic neurons: pharmacological interventions. PMID- 1498853 TI - Anatomical studies of neuropeptide precursor processing enzymes. PMID- 1498854 TI - Combined measures of noradrenergic output and receptor responsivity in depression. PMID- 1498855 TI - Norepinephrine output and metabolism in depressed patients during antidepressant treatments. PMID- 1498857 TI - Memory systems and the brain. PMID- 1498856 TI - CSF noradrenergic activity and sleep EEG in clinically stable schizophrenic patients after haloperidol withdrawal. PMID- 1498858 TI - Drugs as tools for investigating cognition. PMID- 1498859 TI - Public health impact of mental disorders. PMID- 1498860 TI - Scientific advances in the diagnosis and treatment of sleep disorders. PMID- 1498861 TI - Scientific advances and risk benefit issues in the treatment of depressive disorders. PMID- 1498862 TI - Possible drug interactions with reversible MAO inhibitors. PMID- 1498863 TI - Brofaromine, a drug inhibiting MAO-A and 5-HT uptake. PMID- 1498864 TI - Clinical pharmacology of reversible MAO-A inhibitors. PMID- 1498865 TI - The presynaptic serotonin uptake site in depression. PMID- 1498867 TI - Basic models of Alzheimer's disease. PMID- 1498866 TI - Serotonin and sleep regulation. PMID- 1498868 TI - Molecular biology of serotonin receptors and transporters. PMID- 1498869 TI - The selective effects of serotonin reuptake inhibitors. PMID- 1498870 TI - Use of serotonin-active agents in other psychiatric disorders. PMID- 1498871 TI - Effects of hypnotics on sleep regulation and the sleep EEG. PMID- 1498872 TI - Pharmacological control of circadian clock. Pharmacological manipulation of the circadian clock: from animal to human studies. PMID- 1498873 TI - Pharmacological treatment of narcolepsy. PMID- 1498874 TI - HIV-1 associated neurocognitive disorder. The HNRC Group. PMID- 1498875 TI - HIV-1 associated mood and anxiety disorders. PMID- 1498876 TI - HIV-1-associated psychotic disorders. PMID- 1498877 TI - Cross-sectional phase of the WHO Neuropsychiatric AIDS Study: results of cognitive/neuropsychological assessment. PMID- 1498878 TI - Opioid regulation of nociceptive and neuropathic pain. PMID- 1498879 TI - Pharmacological studies of the analgesic effect of antidepressants. PMID- 1498880 TI - The pharmacology of antimigrainous drugs. PMID- 1498881 TI - Melatonin and maternal factors shift the phase of NAT activity rhythm in the pineal gland in rat pups. PMID- 1498882 TI - The mechanism of action of antidepressants in pain treatment: controlled cross over studies in diabetic neuropathy. PMID- 1498883 TI - The thyroid state of depressed patients. PMID- 1498884 TI - Circadian effects on the TSH response to TRH in depressed patients. PMID- 1498885 TI - Subclinical hypothyroidism: recognition, significance, management. PMID- 1498886 TI - The use of T3 to enhance the effects of ECT. PMID- 1498887 TI - Thyroid hormone use to enhance the effects of drugs. PMID- 1498888 TI - Thyroid axis considerations in patients with rapid cycling affective disorder. PMID- 1498889 TI - Correlations between abnormal hippocampal morphology and prefrontal physiology in schizophrenia. PMID- 1498890 TI - Neurological models of schizophrenia--regional implications. PMID- 1498891 TI - Regional brain metabolism as predictors of clozapine response. PMID- 1498892 TI - Aging alters the feedback effects of the activity-rest cycle on the hamster's circadian clock. PMID- 1498893 TI - Regional brain abnormalities associated with specific syndromes of persistent schizophrenic symptoms. PMID- 1498894 TI - Clinical trials with novel treatments of Alzheimer's disease. PMID- 1498895 TI - Pharmacological replacement of cholinergic function in Alzheimer disease. PMID- 1498896 TI - Therapeutic approaches targeted at the amyloid proteins in Alzheimer's disease. PMID- 1498897 TI - EEG mapping in dementia and nootropic drug research. PMID- 1498898 TI - Sleep and biological rhythms in man: a twin study. PMID- 1498899 TI - Quantitative EEG and functional mapping in treatment of major depression. PMID- 1498902 TI - Safety of moclobemide in clinical use. PMID- 1498900 TI - Dose-related and treatment-dependent quantitative EEG effects of antiepileptic compounds in humans. PMID- 1498901 TI - Efficacy and safety of brofaromine in depression: a Canadian multicenter placebo controlled trial and a review of comparative controlled studies. PMID- 1498903 TI - Reversible monoamine oxidase-A inhibitors in resistant major depression. PMID- 1498904 TI - Reversible monoamine-A inhibitors in panic disorder. PMID- 1498905 TI - Reversible MAO inhibitors in social phobia bulimia, and other disorders. PMID- 1498906 TI - The serotonin re-uptake transporter as a target for antidepressant action. PMID- 1498907 TI - Social zeitgebers, biological rhythms and depression. PMID- 1498908 TI - Treatment of resistant depression with 5-HT uptake inhibitors. PMID- 1498909 TI - Course of mood disorders: a challenge to psychopharmacology. PMID- 1498910 TI - Strategies, problems and implications of long-term trials on depression. PMID- 1498911 TI - Lithium and mortality: a 15 year follow-up. PMID- 1498912 TI - Long-term treatment with SSRIs. PMID- 1498913 TI - Impact of affective illness on gene expression: implications for early and long term prophylaxis. PMID- 1498914 TI - Non-acute effects of antidepressants on cognitive and psychomotor performance. PMID- 1498915 TI - Effect of vitamin B12 (mecobalamin) on the circadian rhythm of rat behavior. PMID- 1498916 TI - Cholecystokinin in animal and human brain. PMID- 1498917 TI - Role of CCK in satiety and appetite control. PMID- 1498918 TI - Cholecystokinin and opiate interactions. PMID- 1498919 TI - Cholecystokinin receptors and animal models of anxiety. PMID- 1498920 TI - CCK agonists and antagonists in clinical studies of panic and anxiety. PMID- 1498921 TI - Ethical aspects of psychopharmacological studies in different ethnic groups. PMID- 1498922 TI - Transethnic and transcultural psychopharmacology. PMID- 1498923 TI - WHO cross cultural study on lithium every second day. PMID- 1498924 TI - WHO project on eye movements in patients with schizophrenia. PMID- 1498925 TI - The World Health Organization collaborative study: development of evaluation instruments for the assessment of dementia. PMID- 1498926 TI - Temporal lobe cytoarchitectural neuropathology in schizophrenia. PMID- 1498927 TI - Neurodevelopmental abnormalities in schizophrenia. PMID- 1498928 TI - Precursors of opioid peptides and their gene regulation. PMID- 1498929 TI - Altered orbito-frontal cortex in schizophrenic psychosis. PMID- 1498930 TI - Psychopharmacology and successful cerebral aging. PMID- 1498931 TI - Cholinergic systems in aging: the role of oxidative stress. PMID- 1498932 TI - "Successful" and "usual" aging: an anamnestic, psychodiagnostic and electroencephalogram mapping evaluation. PMID- 1498933 TI - The importance of environmental factors for brain functions in demented patients; implications for normal aging. PMID- 1498934 TI - Clinical and pharmacological approaches to the aging brain (mind). PMID- 1498935 TI - Plasma homovanillic acid and other predictors of clozapine response. PMID- 1498936 TI - Opioid peptides and pain regulation studied in animal models. PMID- 1498937 TI - Serotonergic agents in the treatment of disorders of anxiety and impulse control. PMID- 1498938 TI - Disentangling antidepressant drug actions on anxiety and depression and the relationships to neurochemistry. PMID- 1498939 TI - Definition and classification of age-related cognitive dysfunctions. PMID- 1498940 TI - Cholinergic systems: roles in disease and prospects for therapy. PMID- 1498941 TI - Beta-casomorphins and their significance in behavioural processes. PMID- 1498943 TI - Evidence implicating acetylcholine in neuronal plasticity and in long-term changes in somatosensory cortex following deafferentation. PMID- 1498942 TI - Effect of alpha-glyceril-phosphorylcholine on cerebral glucose metabolism in normal volunteers. PMID- 1498944 TI - Limbic-striatal interactions in reward related processes: modulation by the dopaminergic system. PMID- 1498945 TI - An animal model of anhedonia. PMID- 1498946 TI - Psychobiological substrate of hedonic capacity. PMID- 1498947 TI - Anhedonia in psychotic and non psychotic disorders. PMID- 1498948 TI - Naltrexone in chronic negative schizophrenia. PMID- 1498949 TI - Cigarette smoking, major depression, and schizophrenia. PMID- 1498950 TI - The psychopharmacology of nicotine and its effects on CNS dopamine neurones. PMID- 1498951 TI - Mesolimbic dopamine and incentive properties of nicotine. PMID- 1498952 TI - Sexual behavior, eating and mesolimbic dopamine. PMID- 1498953 TI - Mesoprefrontal cortical dopaminergic activity and prefrontal hypofunction in schizophrenia. PMID- 1498954 TI - Family history and stressors in subtypes of depression. PMID- 1498955 TI - Depression and anxiety: the role of social factors in onset and course. PMID- 1498956 TI - Neuroendocrine factors in affective disorders. PMID- 1498957 TI - Biological and cognitive predictors of response to acute treatment in depressed outpatients. PMID- 1498958 TI - Biological measures as predictors of response to pharmacotherapy and psychotherapy. PMID- 1498959 TI - Opioid peptides in psychiatric disorders. PMID- 1498961 TI - Hormones and the plasticity of neurons. PMID- 1498960 TI - Association and linkage studies in bipolar affective disorder. PMID- 1498962 TI - The hypothalamic-pituitary-adrenocortical (HPA) system and anti-depressive drug (AD) action. PMID- 1498963 TI - Antidepressant regulation of glucocorticoid receptor gene expression. PMID- 1498964 TI - Measurement of the effects of antidementia agents. PMID- 1498965 TI - Time perception as a useful tool for measuring drug effects unrelated to vigilance and sedation. PMID- 1498966 TI - Psychometrics of enhanced psychological function. PMID- 1498967 TI - Effects of psychoactive drugs on car driving performance: drugs in crash-involved drivers. PMID- 1498968 TI - The role of neuropeptides in the pathophysiology of affective disorders. PMID- 1498969 TI - Measurement of quality of life in dementia drug trials. PMID- 1498970 TI - Inositol passes the blood brain behavior sufficiently to reverse lithium effects on behavior in rats. PMID- 1498971 TI - Effects of lithium on signal transduction in humans. PMID- 1498972 TI - Targets for lithium action in the brain: protein kinase C substrates and muscarinic receptor regulation. PMID- 1498973 TI - Interaction between dopaminergic and serotonergic systems. PMID- 1498974 TI - The interrelationship of serotonin and norepinephrine in man. PMID- 1498975 TI - Dysphoric mood. PMID- 1498976 TI - The psychobiology of dysphoric mania. PMID- 1498977 TI - Psychotic mixed states. PMID- 1498978 TI - The sources of characterologic presentations of mixed bipolar states. PMID- 1498979 TI - The distinctive mixed states of bipolar I, II, and III. PMID- 1498980 TI - The somatization spectrum and antidepressant response in the medically ill. PMID- 1498981 TI - Antidepressants in pain treatment: antidepressant or analgesic effect? PMID- 1498982 TI - Depression and antidepressants in patients with brain injury. PMID- 1498983 TI - Serotonergic and dopaminergic involvement in ethanol intake. PMID- 1498984 TI - Antidepressants in the cardiac patient. PMID- 1498985 TI - Drug interactions and pharmacokinetic risk factors when using antidepressants in the medically ill patients. PMID- 1498986 TI - Changes of drug biodistribution in the methamphetamine sensitized rat brain. PMID- 1498987 TI - Behavioral neurobiological effects of chronic cocaine administration: contrasts between administration paradigms as well as times after withdrawal. PMID- 1498988 TI - Conditioned components of cocaine sensitization. PMID- 1498989 TI - Stress, depression and natural killer cells: potential clinical relevance. PMID- 1498990 TI - The expression of genetic differences in social behavior in ICR mice correlates with differences in cellular immune responsiveness. PMID- 1498991 TI - Conditioning mechanisms in drug dependence. PMID- 1498992 TI - Neuropsychiatric aspects of HIV infection. PMID- 1498993 TI - Interleukin-1: effects in the central nervous system and relevance to AIDS. PMID- 1498994 TI - The immune-adrenal feedback: basic aspects. PMID- 1498995 TI - The electrophysiology of ECT: relevance to mechanism of action. PMID- 1498996 TI - Serotonergic mechanisms of ECT: neuroendocrine evidence. PMID- 1498998 TI - Pharmacological analysis of drug dependence. PMID- 1498997 TI - Monoaminergic actions of ECT. PMID- 1498999 TI - Pharmacological approaches to cocaine dependence. PMID- 1499000 TI - Gut peptides and the control of meal size in humans. PMID- 1499001 TI - Genetic contributions to alcoholism. PMID- 1499002 TI - Novel neuropharmacological treatments of alcohol dependence. PMID- 1499003 TI - Pharmacogenetics in psychopharmacology: basic principles and clinical implications. PMID- 1499004 TI - Metabolic interaction between tricyclic antidepressant and fluvoxamine and fluoxetine, a pharmacogenetic approach. PMID- 1499005 TI - Pharmacogenetics of tricyclic and novel antidepressants: recent developments. PMID- 1499006 TI - Pharmacokinetics of fluoxetine and fluvoxamine in depressed patients: personal results. PMID- 1499008 TI - Clinical relevance of phenotyping groups of patients for psychotropic drug trials. PMID- 1499007 TI - Genetic factors in the metabolism of haloperidol. PMID- 1499009 TI - Comorbidity of recurrent brief depression. PMID- 1499010 TI - Serotonin receptor subtypes and affective disorders. PMID- 1499011 TI - Serotonin receptor subtypes: neuroendocrine regulation in depression. PMID- 1499012 TI - Serotonin receptor down regulation by antidepressants: platelet and neuroendocrine markers in humans. PMID- 1499013 TI - Serotonergic antidepressants--past, present, and future. PMID- 1499014 TI - Novel serotonergic mechanisms and clinical experience with nefazodone. PMID- 1499015 TI - Primary structure of four human milk octa-, nona-, and undeca-saccharides established by 1H- and 13C-nuclear magnetic resonance spectroscopy. AB - The structures of two octasaccharides, one nonasaccharide, and one undecasaccharide, isolated from human milk, have been investigated by 1H- and 13C nuclear magnetic resonance spectroscopy. The structures of these oligosaccharides are: beta-D-Galp-(1----4)-[alpha-L-Fucp- (1----3)]-beta-D-GlcpNAc-(1----3)-beta-D Galp-(1----4)-[alpha-L-Fucp+ ++- (1----3)]-beta-D-GlcpNAc-(1----3)-beta-D-Galp-(1 ---4)-D-Glc; beta-D-GALp-(1----3)-[alpha-L-Fucp-(1----4)]-beta-D-GlcpNAc-(1---- 3)-beta-D - Galp-(1----4)-[alpha-L-Fucp-(1----3)]-beta-D-GlcpNAc-(1----3)-beta -D Galp- (1----4)-D-Glc; beta-D-Galp-(1----4)-[alpha-L-Fucp-(1----3)]-beta-D-GlcpNAc (1---- 6)-(alpha - L-Fucp-(1----2)-beta-D-Gal-(1----3)-[alpha-L-Fucp-(1----4)]- beta-D-GlcpNAc- (1----3))-beta-D-Galp-(1----4)-D-Glc; and alpha-L-Fucp-(1----2) beta-D-Galp-(1----3)-beta-D-GlcpNAc-(1----3) -beta-D- Galp-(1----4)-[alpha-L-Fucp (1----3)]-beta-D-GlcpNAc-(1----6)-[alp ha-L- Fucp-(1----2)-beta-D-Galp-(1----3) beta-D-GlcpNAc-(1----3)]-beta-D -Galp- (1----4)-D-Glc. The two octasaccharides have been previously isolated from human milk as a mixture, and in a pure form from new-born feces, but the n.m.r. data were not provided. These two octasaccharides display the di-Lewis X and the composite Lewis A-Lewis X antigenic determinant, previously described as neo-antigens of adenocarcinoma cell lines. PMID- 1499016 TI - Synthesis and characterization of 6-O-beta-lactosyl-alpha,beta-lactoses, 1-O-(6-O beta-lactosyl-beta-lactosyl)-(R,S)-glycerols, and 4,6-di-O-beta-D galactopyranosyl-alpha,beta-D-glucoses. AB - 1,2,3,2',3',4',6'-Hepta-O-acetyl-beta-lactose (4) was coupled with 2,3,6,2',3',4',6'-hepta-O-acetyl-alpha-lactosyl bromide (7) in the presence of Hg(CN)2 to afford 1,2,3,2',3',4',6'-hepta-O-acetyl-6-O-(2,3,6,2',3',4',6'-hepta-O acetyl-b eta- lactosyl)-beta-lactose (11) which, upon O-deacetylation, gave 6-O beta-lactosyl-alpha,beta-lactoses (64% from 4). In contrast, the reaction of 7 with benzyl 2,3,2',3',4',6'-hexa-O-acetyl-beta-lactoside in the presence of Hg(CN)2 produced 3,6,2',3',4',6'-hexa-O-acetyl-1,2-O- (2,3,2',3',4',6'-hexa-O acetyl-1-O-benzyl-beta-lactos-6-yl orthoacetyl)-alpha-lactose (63%) and 3,6,2',3',4',6'-hexa-O-acetyl-1,2-O-(1- cyanoethylidene)-alpha-lactose (27%). The glycosidation of 4 using 2,3,4,6-tetra-O-acetyl-alpha-D-galactopyranosyl bromide in the presence of Hg(CN)2 afforded, after deprotection, 4,6-di-O-beta-D galactopyranosyl-alpha,beta-D-glucoses (66%). The reaction of 11 with 1,2-di-O benzyl-(R,S)-glycerols and trimethylsilyl trifluoromethanesulfonate yielded, after deprotection, 1-O-(6-O-beta-lactosyl-beta-lactosyl)-(R,S)-glycerols (18%). Under the same coupling conditions 11 reacted with 2-O-benzylglycerol to form 3-O acetyl-2-O-benzyl-1-O-[2',3',4',6'-hexa-O-acetyl-6-O-(2,3,6,2',3',4' ,6'- hepta-O acetyl-beta-lactosyl)-beta-lactosyl]-(R,S)-glycerols (16%). PMID- 1499017 TI - Evidence that the acidic polysaccharide secreted by Agrobacterium radiobacter (ATCC 53271) has a seventeen glycosyl-residue repeating unit. AB - The extracellular anionic polysaccharide produced by the bacterium Agrobacterium radiobacter (ATCC 53271) contains D-galactose, D-glucose, and pyruvic acid in the molar ratio 2:15:2. Analysis of the methylated polysaccharide indicated the presence of terminal, non-reducing glucosyl, 3-, 4-, 6-, 2,4-, and 4,6-linked glucosyl residues, 3-linked 4,6-O-[(S)-1-carboxyethylidene]glucosyl residues, and 3-linked galactosyl residues. Partial acid hydrolysis of the methylated polysaccharide, followed by reduction with NaB2H4 and then O-ethylation, gave a mixture of alkylated oligoglycosyl alditols that were separated by reversed-phase h.p.l.c. and analyzed by 1H-n.m.r. spectroscopy, g.l.c.-m.s., and glycosyl linkage composition analysis. Smith degradation of the polysaccharide gave three diglycosyl alditols that were separated by semi-preparative, high-pH anion exchange chromatography, and were analyzed by 1H-n.m.r. spectroscopy, g.l.c. m.s., and glycosyl-linkage composition analysis. The polymer obtained by NaBH4 reduction of the periodate-oxidized polysaccharide was methylated, and the noncyclic acetals were hydrolyzed with aq. 90% formic acid to generate a mixture of partially O-methylated mono- and di-glycosyl alditols. The partially O methylated oligoglycosyl alditols were O-ethylated. The resulting alkylated oligoglycosyl alditols were separated by reverse-phase h.p.l.c. and then characterized by 1H-n.m.r. spectroscopy, g.l.c.-m.s., and glycosyl-linkage composition analysis. The results from the studies described here provide strong evidence that the acidic polysaccharide secreted by A. radiobacter (ATCC 53271) has a heptadecasaccharide repeating unit. PMID- 1499018 TI - Elucidation of the structure and conformation of a methylated tetrasaccharide alditol acetate by n.m.r. spectroscopy. AB - The structure of the methylated derivative (1) of the tetrasaccharide-alditol-O beta-L-rhamnopyranosyl-(1----3)-O-beta-D- xylopyranosyl-(1----4)-O-beta-L rhamnopyranosyl-(1----2)-1,5-di-O-acetyl -L- arabinitol has been determined solely on the basis of n.m.r. data. PMID- 1499019 TI - A general radical-mediated stereoselective route for the construction of chiral furo[2,3-b]furans from D-xylose. PMID- 1499020 TI - Crystal structure and n.m.r. analysis of lactulose trihydrate. AB - The 13C CPMAS n.m.r. spectrum of 4-O-beta-D-galactopyranosyl-D-fructose (lactulose) trihydrate, C12H22O11.3 H2O, identifies the isomer in the crystals as the beta-furanose. This is confirmed by a crystal structure analysis, using CuK alpha X-ray data at room temperature. The space group is P212121, with Z = 4 and cell dimensions a = 9.6251(3), b = 12.8096(3), c = 17.7563(4) A. The structure was refined to R = 0.031 and Rw 0.025 for 1929 observed structure amplitudes. All the hydrogen atoms were unambigously located on difference syntheses. The conformation of the pyranose ring is the normal 4C1 chair and that of the furanose ring is 4T3. The 1----4 linkage torsion angles are O-5'-C-1'-O-1'-C-4 = 79.9(2) degrees and C-1'-O-1'-C-4-C-5 = -170.3(2) degrees. All hydroxyls, ring and glycosidic oxygens, and water molecules are involved in the hydrogen bonding, which consists of infinite chains linked together by water molecules to form a three-dimensional network. There is a three-centered intramolecular, interresidue hydrogen bond from O-3-H to O-5' and O-6'. The n.m.r. spectrum of the amorphous, dehydrated trihydrate suggests the occurrence of a solid-state reaction forming the same isomeric mixture as was observed in crystalline anhydrous lactulose, although the mutarotation of the trihydrate when dissolved in Me2SO is very slow. PMID- 1499021 TI - The crystal structure of lithium L-ascorbate dihydrate. AB - The crystal structure of lithium L-ascorbate dihydrate is triclinic, Pl; with a = 5.964(9), b = 5.299(9), c = 7.760(15) A; alpha = 100.82(9), beta = 109.78(9), gamma = 92.02(9) degrees. The plant fragment of the ascorbate anion is a part of the five-membered ring [C-1,C-2,C-3(O-3),C-4], and O-4 deviates by 0.053(2) A from this plane. Deprotonated O-3 is an acceptor of three hydrogen bonds, but does not interact with Li+. The coordination number of the Li+ is 5 and it is bonded to two water molecules and three hydroxyl oxygen atoms of two ascorbate anions: O-2 and the gauche O-5, 6 of the side chain. PMID- 1499022 TI - Regio- and stereo-selective synthesis of carbohydrate isoxazolidines by 1,3 dipolar cycloaddition of nitrones to 5,6-dideoxy-1,2-O-isopropylidene- alpha-D xylo-hex-5-enofuranose. AB - The synthesis of 2-phenyl-3-aryl and 2-phenyl-3-aroyl derivatives 5-(1,2-O isopropylidene-alpha-D-xylo-tetrofuranos-4-yl)isoxazolidi ne (3) from nitrones and 5,6-dideoxy-1,2-O-isopropylidene-alpha-D-xylo-hex-5- enofuranose (1) is described. The 1,3-dipolar cycloaddition reactions given mainly anti adducts 3 and 4 (greater than or equal to 95% pi-facial stereoselectivity). The cycloadducts 3 with H-3,5 cis are formed either exclusively or preponderate over the trans diastereoisomers 4. PMID- 1499023 TI - Radical cyclisation of hept-1-enitols. AB - 7-Deoxy-7-iodohept-1-enitols react intramolecularly to give 5-carba analogues of pyranoses (pseudo sugars) by the action of tributyltin hydride, which generates a radical at C-7. The configuration at the new chiral centre depends on the relative orientation of the oxygen functions in the starting material and the pattern of substitution. PMID- 1499024 TI - Synthesis and enzyme-inhibitory activity of methyl acarviosin analogues having the alpha-manno configuration. AB - Two methyl acarviosin analogues 3a and 4a, having the alpha-manno configuration, and their dihydro derivatives 6a and 7a were synthesised by coupling the protected pseudo-sugar epoxides with methyl 4-amino-4-deoxy- and -4,6-dideoxy alpha-D-mannopyranoside. Similarly, two analogous compounds 5a and 8a composed of the 1,6-anhydro-beta-D-mannopyranose residues were prepared. Compound 7a showed mild inhibitory activity against Jack bean alpha-D-mannosidase, and 3a was a moderate inhibitor of both alpha-D-mannosidase and yeast alpha-D-glucosidase. PMID- 1499025 TI - Synthesis of oligosaccharides containing the X-antigenic trisaccharide (alpha-L Fucp-(1----3)-[beta-D-Galp-(1----4)]-beta-D-GlcpNAc) at their nonreducing ends. AB - The "armed" methyl 2,3,4-tri-O-benzyl-1-thio-beta-L-fucopyranoside was reacted with "disarmed" phenyl O-(tetra-O-acetyl-beta-D-galactopyranosyl)-(1----4)-6-O benzyl-2- deoxy-2-phthalimido-1-thio-beta-D-glucopyranoside in the presence of CuBr2-Bu4NBr complex to give phenyl O-(2,3,4,6-tetra-O-acetyl-beta-D galactopyranosyl)-(1----4)-O- [(2,3,4-tri-O-benzyl-alpha-L-fucopyranosyl)-(1--- 3])-6-O-benzyl-2-deoxy -2- phthalimido-1-thio-beta-D-glucopyranoside (6) as a novel glycosyl donor. The glycosylating capability of 6 was further examined using N-iodosuccinimide-triflic acid as a reagent. This led to the synthesis of a tetrasaccharide and a pentasaccharide incorporating the X-antigenic structure represented by 6. PMID- 1499026 TI - Professor David John Manners. PMID- 1499027 TI - Special issue in honour of Professor David John Manners. PMID- 1499028 TI - The polysaccharides of agricultural lupin seeds. AB - The polysaccharides of the seeds of four species of agricultural lupin have been shown to comprise galactans, arabinogalactans, arabinans, rhamnogalacturonans, and galactoxyloglucans. Low molecular weight compounds were present in the mixtures after methylation of the acidic polysaccharides. Three tri-O-acetyl-O methylhexuronic acids, with one hydroxyl group unsubstituted, formed during methylation, hydrolysis, and acetylation of the acidic polysaccharides, were present in high and variable proportions. PMID- 1499029 TI - Roles of the aromatic side chains in the binding of substrates, inhibitors, and cyclomalto-oligosaccharides to the glucoamylase from Aspergillus niger probed by perturbation difference spectroscopy, chemical modification, and mutagenesis. AB - The roles of the aromatic side chains of the glucoamylase from Aspergillus niger in the binding of ligands, as determined by difference spectroscopy using four types of inhibitors (a) valienamine-derived, (b) 1-deoxynojirimycins, (c) D glucono-1,5-lactone, and (d) maltitol, two types of disaccharide substrates (a) alpha-(1----4)-linked and (b) alpha-(1----6)-linked, and three cyclomalto oligosaccharides (cyclodextrins, CDs) are discussed. An unusual change in absorbance from 300 to 310-320 nm, obtained only with the valienamine-derived inhibitors or when D-glucono-1,5-lactone and maltose are combined, is concluded to arise when subsite 2 is occupied in a transition-state-type of complex. The single mutations of two residues thought to be involved in binding, namely, Tyr116----Ala and Trp120----Phe, alter, but do not abolish this perturbation. The perturbations in the spectra also suggest that maltose and isomaltose have different modes of binding. The following Kd values (M) were determined: acarbose, less than 6 x 10(-12); methyl acarviosinide, 1.6 x 10(-6); and the D gluco and L-ido forms of hydrogenated acarbose, 1.4 x 10(-8) and 5.2 x 10(-6), respectively. Therefore, both the valienamine moiety and the chain length of acarbose are important for tight binding. In contrast to the valienamine-derived inhibitors, none of the 1-deoxynojirimycin type protected glucoamylase against inactivating oxidation of tryptophanyl residues, although each had a Kd value of approximately 4 x 10(-6) M. There are two distinct carbohydrate-binding areas in glucoamylase, namely, the active site in the catalytic domain and a starch granule-binding site in the C-terminal domain. The alpha-, beta-, and gamma-CDs have high affinity for the starch-binding domain and low affinity for the active site, whereas the reverse was found for acarbose. PMID- 1499030 TI - Structural characterization of an arabinoxylan-rhamnogalacturonan complex from cell walls of Zea shoots. AB - An arabinoxylan-rhamnogalacturonan complex, comprised of galacturonic acid, rhamnose, arabinose, xylose, and galactose in the ratios 75.9:4.6:5.2:3.5:5.4 and lesser amounts of other constituents, was dissociated from the water-insoluble matrix of cell walls of Zea mays by xylanase and glucuronoxylanase treatment. The solubilized complex retained its integrity when subjected to a series of separation procedures, and analysis of the sugar components throughout the elution profiles exhibited consistent ratios. The complex was subjected to controlled degradation by pectate lyase and pectin lyase, yielding two components comprised of rhamnose, fucose, arabinose, xylose, galactose, and galacturonic acid in the ratios 10.9:1.5:13.1:16.9:27.7:30.0 and 8.5:1.7:11.8:6.6:17.3:54.0, respectively, in addition to di-, tri-, and tetra-saccharides of galacturonic acid. The non-reducing terminals of the latter were characterized by the presence of 4,5-unsaturated hexuronic acid. The structural features of the two complex fractions were partially characterized. PMID- 1499031 TI - The substrate specificity of isoamylase and the preparation of apo-glycogenin. AB - A new facet of the specificity of the glycogen-debranching enzyme, isoamylase, namely, the hydrolysis of a carbohydrate-amino acid linkage, is described. This bond joins the terminal, reducing-end D-glucose unit of glycogen to the hydroxyl group of tyrosine in glycogenin, the primer protein for glycogen biogenesis. The specificity was further defined by demonstrating that 4-nitrophenyl alpha maltotrioside and higher homologs also act as substrates. The splitting of the glycogen-glycogenin bond by isoamylase indicates the alpha-anomeric configuration of the terminal D-glucose unit. It also provides a means of preparing apo glycogenin. Pullulanase, a somewhat similar starch- and glycogen-debranching enzyme, does not split these new isoamylase substrates, permitting the 4 nitrophenyl saccharides to be used in distinguishing between isoamylase and pullulanase. PMID- 1499033 TI - Conformation of 3-O-beta-D-galactopyranosyl-L-arabinose and a comparison with its alpha-linked isomer. PMID- 1499032 TI - Molecular and metabolic aspects of lysosomal glycogen. AB - The high molecular weight glycogen associated with the lysosomal compartment in glycogen storage disease type VIII is more resistant to degradation by proteinase than normal glycogen. The assembly of large glycogen particles on disulphide linked protein backbones has been confirmed and the disulphide-reducing nature of the lysosome appears to confer an advantage in the amylolytic degradation of glycogen. Experiments utilising acarbose, a lysosomal (1----4)-alpha-D glucosidase inhibitor, show that some blood glucose could arise in normal mammals from extra-hepatic tissue, by degradation of the glycogen in the lysosomal compartment. PMID- 1499034 TI - A re-investigation of the borohydride reduction of carbohydrates. PMID- 1499035 TI - Heterogeneity of the glucoamylase components of the raw-starch-digesting amylase from Chalara paradoxa. PMID- 1499036 TI - Characterization of seven xyloglucan oligosaccharides containing from seventeen to twenty glycosyl residues. AB - The complete primary structures of seven oligosaccharide subunits of the xyloglucan secreted by suspension-cultured Acer pseudoplatanus cells were determined. The oligosaccharides, ranging in size from 17 to 20 glycosyl residues, were generated by treatment of the xyloglucan with an endo-beta-(1--- 4)-glucanase. The oligosaccharide components of a fraction obtained by Bio-Gel P 2 chromatography of enzyme-treated xyloglucan were further purified by normal phase h.p.l.c. and then converted to the corresponding oligoglycosyl alditols by reduction with NaBH4. The oligoglycosyl alditols, after purification to near homogeneity by reversed-phase h.p.l.c., were structurally characterized by 1H n.m.r. spectroscopy, fast-atom bombardment mass spectrometry (f.a.b.-m.s.), and analysis of their glycosyl-residue and glycosyl-linkage compositions. Novel structural elements of xyloglucans were observed in this study, including beta-D xylopyranosyl and alpha-L-arabinofuranosyl-(1----3)-beta-D-xylopyranosyl sidechains. The results also extend our list of correlations between 1H-n.m.r. resonances and specific structural features of xyloglucans and thus enhance our ability to determine the structures of xyloglucans from various sources. PMID- 1499037 TI - Reinvestigation of the binding of proflavine to DNA. Is intercalation the dominant binding effect? AB - The binding isotherms of the acridine dye proflavine (PF) to calf-thymus DNA have been carefully redetermined at pH = 6.5 and 25 degrees C. Bound monomers (M), dimers and trimers (D,T) as well as higher polymeric PF cations (P) could be distinguished by absorption spectroscopy. The concentrations of these species were determined as a function of the concentration CMf of free PF cations in solution. NaCl is a competitor (S) for the bound dye cations. The competitive salt effect has been carefully studied in the wide concentration range 0 less than or equal to Cs less than or equal to 1 M. - At very low dye concentrations CMf monomeric and dimeric PF cations M and D are bound to DNA. The binding constant KM of the monomers M depends strongly on the concentration Cs of the competitor and decreases with increasing Cs to a limiting value greater zero. We have developed an extended equilibrium model for the quantitative description of this competitive salt effect. We assume that two types 1 and 2 of the bound monomers exist already at very low CMf and that they can be distinguished by the competitive salt effect: The intercalated monomers 1 are resistant to competitors whereas the pre-intercalatively bound monomers 2 are displaced by Na+ cations. The binding constants of 1 and 2 have been determined by the use of the equilibrium model: KM1 = 3.5 x 10(4) M-1, KM2* = 2.7 x 10(6) M-1. Thus, the binding constant KM1 of the intercalation 1 is very much smaller than the binding constant KM2* of the pre-intercalative bond 2. This is in contradiction to the generally accepted notion that intercalation should be the dominant binding effect. The concentration of bound monomers decreases rapidly with increasing CMf. Instead, DNA-bound dimers D and subsequently trimers T are observed. Both species are very sensitive to competitor cations. We have determined the dependence of the concentrations of bound D and T on the competitor concentration Cs using the extended equilibrium model. The respective binding constants are KD* = 8.7 x 10(4) M-1 and KT* = 2.4 x 10(4) M-1. Finally D and T disappear with increasing CMf. At higher dye concentrations, higher dye polymers P are observed instead of D and T. In contrast to D and T, the binding of P is favoured by cooperative effects.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1499038 TI - Localization of actin in normal human hepatocytes using fluorescent phallotoxins and immunohistochemical amplification. AB - Two different methods, fluorescent phallotoxins and immunohistochemical amplification systems were used to visualize actin in normal human hepatocytes. With fluorescent phallotoxins (NBD-phallacidin or rhodamine phalloidin), F-actin was distributed along the plasma membranes and at the bile canaliculi. With immunohistochemical methods (biotin-avidin, biotin-streptavidin, silver enhancement), actin was found at the same level, however a cytoplasmic staining was observed and discussed as G-actin localization. PMID- 1499039 TI - Blood banking-induced senescent modifications on red blood cells. AB - In the past few years significant progress has been made in the extension of storage time for red blood cells (RBCs). Albeit this, membrane still undergoes damage during conservation under blood bank conditions, reducing red cell viability following transfusion. Consequently in this study, we evaluated the presence of senescence indices (appearing on RBCs during in vivo aging) on blood bank stored RBCs, more precisely the 4.1a/4.1b ratio and the binding of autologous immunoglobulins. Although not significant, a slight increase (0.995 +/ 0.070 to 1.008 +/- 0.058) was observed in the 4.1a/4.1b ratio during the first three weeks of storage. A rapid and significant (p less than 0.001) increase in the number of cell-bound IgGs (91 +/- 22 to 913 +/- 92), following incubation with purified autologous IgGs, was observed in the first days of storage. Thus, following transfusion, binding of autologous IgGs to stored RBCs could influence post-transfusion viability. PMID- 1499040 TI - The effect of a mannose binding protein on macrophage interactions with Candida albicans. AB - A soluble mannose binding protein (MBP), obtained from rabbit serum, was found to inhibit phagocytosis of Candida albicans by bone marrow derived, cultured murine macrophages. During in vitro incubation of yeast with lymphocyte-free macrophage populations uptake of the yeast was significantly reduced at MBP concentrations of 5 micrograms/ml. A similar reduction in yeast phagocytosis was produced by dextrose, d-fucose, l-fucose, d-mannose and alpha-methyl-d-mannoside but required saccharide concentrations of 25-50 mg/ml. Inhibition of phagocytosis of the yeast also resulted from pretreatment of either the macrophages or the yeasts with MBP followed by washing. As expected, the addition of mannan to the assay medium blocked the inhibitory effect of MBP for uptake of C. albicans. These findings suggest that both cell bound and soluble mannose receptors may be important modulators of macrophage-Candida interactions. PMID- 1499041 TI - Experimental calcification in rat submandibular gland. AB - The present study describes the phenomenon of calciphylaxis, rapid calcification due to treatment with sensitizer dihydrotachysterol (DHT) and challenging agent 5 hydroxytryptamine (5-HT) in the rat submandibular gland (SMG) in terms of light and electron microscopy, and histochemistry. For biophysical analysis of the calcified bodies, X-ray microanalysis (XMA) and X-ray powdered diffraction methods were used. The calcified lesions in the salivary glands were histologically divided into 3 types: type 1, calcification of basal membranes in duct-like structures; type 2, granular calcified materials with remarkable necrotic changes in cell, containing 3 kinds of small vesicular structures observed in electron microscopy; and type 3, von Kossa's positive structures containing needle-like crystalline and electron-dense amorphous materials. Con A and UEA-1 lectin staining reactions were strong in the type 1 and 2 lesions. These findings suggest that the calcification matrix may contain mannose, fucose and glucose. The X-ray microanalysis of calcified materials revealed the magnesium whitelockite pattern, the type 3 displayed high quantities of Ca, P, and Mg ions comparing with the type 1 and 2, and the X-ray diffraction showed the hydroxyapatite pattern. We suggest that the above changes may be categorized as dystrophic calcification due to necrotic alterations brought about by the hypercalcaemic condition. PMID- 1499042 TI - Possible involvement of arachidonic acid metabolites in the synergistic action of endothelial mitogenesis by basic fibroblast growth factor and phorbol ester. AB - Our object was to obtain information about the regulatory mechanism which modulates the effect of basic fibroblast growth factor (bFGF) on commitment to growth in human umbilical vein endothelial (HUVE) cells. Firstly, phorbol ester PMA, a known activator of protein kinase C (PKC), was found to be able to act synergistically with bFGF to stimulate 3H thymidine incorporation in HUVE cells. Secondly, bFGF and PMA induced a stimulated phospholipase A2 (PLA2)-catalyzed release of 14C arachidonate. Thirdly, inhibitors of PLA2, PKC and HETE, but not an inhibitor of cyclooxygenase metabolites, inhibited FGF/PMA-stimulated DNA synthesis. Fourth, the stable cyclooxygenase metabolite of prostacyclin was not found to be changed when cells were treated with bFGF plus PMA. The present data suggest that PKC is able of acting synergistically with bFGF in order to stimulate DNA-primary initiation activity in HUVE cells via the PLA2-dependent generation of lipoxygenase metabolites such as HETE. PMID- 1499043 TI - Lipid peroxidation causes an increase of lipid order and a decrease of 5' nucleotidase activity in the liver plasma membrane. AB - The effect of peroxidation on 5'-nucleotidase activity as well as on membrane microviscosity has been investigated in liver plasma membranes from Wistar rats. The peroxidation was performed with 100 microM H2O2 and 200 microM FeSO4 and/or with 5 mM t-butylhydroperoxide. Treatment of the membranes with these oxidizing agents resulted in an elevation of the transition temperatures of the polarization of the lipid fluorescent probes 1,6 diphenyl-1,3,5 hexatriene (DPH), 3-p-(6-phenyl) 1,3,5 hexatriene phenylpropionic acid (PA-DPH) as well as of the fluorescent thiol reagent N-(1-pyrene) maleimide (1-PM). The peroxidation resulted in a decrease of the activity of 5'nucleotidase. Our data support that the increase of membrane microviscosity of the lipid domain regulates the activity of 5'-nucleotidase. PMID- 1499044 TI - A comparative enzyme histochemical study of glucose metabolism in the conduction system of mammalian hearts. AB - A histochemical study of some enzymes of glucose metabolism was performed on the heart conduction system of rat, dog, rabbit, pig, calf and lamb. Histochemical activities revealed a higher rate of anaerobic metabolism and a lower rate of aerobic metabolism in the conducting cells in comparison with the working myocardial fibres. An increase of the histochemical activities from the atrioventricular node to the distal portions of bundle branches was noted. The importance of the high glycogen content and the high phosphorylase activity in the heart conduction system was discussed. PMID- 1499045 TI - (ADP-ribosyl)ation pattern of chromosomal proteins during ageing. AB - (ADP-ribosyl)ation of chromosomal proteins was studied by incubating the nuclei of brain and liver of young and old rats with 14C-NAD+. In brain as well as in liver histone proteins show approximately 2-3 fold higher (ADP-ribosyl)ation than that of non-histone chromosomal (NHC) proteins of both the age groups. H1 seems to be the major target for (ADP-ribosyl)ation. Amongst nucleosomal histones H2B is the main acceptor of 14C-labelled ADP-ribose moieties. A sharp age related decline of (ADP-ribosyl)ation of chromosomal proteins was observed in both the tissues. PMID- 1499046 TI - Distribution and coexistence of chromogranin A-, serotonin- and pancreastatin like immunoreactivity in endocrine-like cells of the human anal canal. AB - The comparative distribution and coexistence of chromogranin A (CGA)-, serotonin (5-hydroxytryptamine; 5-HT)- and pancreastatin (PST)-like immunoreactivity in endocrine-like cells of the human anal canal was investigated by light microscopic immunocytochemistry. The largest population of colorectal endocrine like cells consisted of CGA-immunoreactive (ir) cells, followed by the 5-HT-ir and PST-ir cell population. In the anal transitional zone (ATZ), CGA- and 5-HT immunoreactivity was equally distributed; ir-PST was confined to a smaller endocrine-like cell population. In the squamous zone and the perianal skin, Merkel cells in the basal layer of the epidermis and hair follicles exhibited ir CGA and ir-PST but no ir-5-HT. Double immunofluorescence on identical sections revealed distinct coexistence patterns. In the colorectal zone, about 2/3 of the CGA-ir endocrine-like cells also stained for 5-HT, whereas in the ATZ epithelium, CGA- and 5-HT-immunoreactivity completely overlapped. No 5-HT-immunoreactivity could be detected in CGA-ir Merkel cells of the squamous zone of the anal canal and the perianal skin. PST-immunoreactivity was present in about 1/3 of the CGA ir colorectal and anal transitional endocrine-like cells and in about 1/4 of the Merkel-cell population staining for CGA. These chemically heterogeneous phenotypes of the anal endocrine-like and Merkel cells may reflect a specific regulatory role of these cells in the various epithelial linings of the human anal canal and the perianal skin. PMID- 1499047 TI - Renin processing studied by immunogold localization of prorenin and renin in granular juxtaglomerular cells in mice treated with enalapril. AB - Immunogold techniques were used to investigate renin processing within granular juxtaglomerular cells following short-term (6 h and 1 day) and long-term (4 weeks) enalapril treatment in female BALB/c mice. In control animals, renin protein labelling was localized to all types of granules (proto-, polymorphous, intermediate and mature) and to transport vesicles, whilst prorenin labelling was found in all these sites except mature granules, confirming that active renin is localized to mature granules only. Following short-term enalapril treatment, the exocytosis of renin protein from mature granules was increased. Long-term enalapril treatment resulted in increased numbers of transport vesicles and all types of granules, consistent with increased synthesis and storage of renin. More large intermediate granules contained discrete regions labelled for prorenin. Renin protein was exocytosed from individual and multiple granules, whilst prorenin was exocytosed from proto- and intermediate granules. It is concluded that under normal conditions prorenin is secreted constitutively by bulk flow from transport vesicles. On the other hand, active renin is secreted regulatively from mature granules. In conditions of intense stimulation (angiotensin converting enzyme inhibition treatment), increased synthesis of prorenin leads to enhanced secretion of prorenin by both constitutive and regulative pathways. Under these conditions, the conversion of prorenin to active renin is increased, with increased secretion of active renin occurring in a regulative manner. Furthermore, the localization of prorenin to one discrete region of large intermediate granules leads us to conclude, that cleavage of the prosegment of renin occurs with the transition of intermediate to mature granules. PMID- 1499048 TI - Changes in the extracellular matrix of the normal human breast during the menstrual cycle. AB - The normal human mammary gland undergoes a well defined sequence of histological changes in both epithelial and stromal compartments during the menstrual cycle. Studies in vitro have suggested that the extracellular matrix surrounding the individual cells plays a central role in modulating a wide variety of cellular events, including proliferation, differentiation and gene expression. We therefore investigated the distribution of a number of extracellular matrix molecules in the normal breast during the menstrual cycle. By use of indirect immunofluorescence, with specific antibodies, we demonstrated that laminin, heparan sulphate proteoglycan, type IV collagen, type V collagen, chondroitin sulphate and fibronectin undergo changes in distribution during the menstrual cycle, whereas collagen types I, III, VI and VII remain unchanged. These changes were most marked in the basement membrane, sub-basement membrane zone and delimiting layer of fibroblasts surrounding the ductules where basement membrane markers such as laminin, heparan sulphate proteoglycan, and type IV and V collagens appear greatly reduced during the mid-cycle period (days 8 to 22). These results suggest that some extracellular matrix molecules may act as mediators in the hormonal control of the mammary gland, whereas others may have a predominantly structural role. PMID- 1499049 TI - Multinucleated giant cells in primary cultures derived from canine bone marrow- evidence for formation of putative osteoclasts. AB - Mononucleated cells derived from canine bone marrow were maintained in vitro for up to 6 weeks. The culture characteristics and development of these cells were evaluated by histological, ultrastructural and histochemical methods. Within 1 week the cells had fused together to form flattened, multinucleated cells. Further fusing with one another and other mononucleated cells produced large (diameters more than 300 microns), multinucleated cells which frequently contained more than 50 nuclei per cell and exhibited ultrastructural and histochemical features that were strikingly similar to those displayed by osteoclasts. The confluent monolayer of mono- and multinucleated cells present at 4 weeks had, by the sixth week, become altered such that fibroblast overgrowth obliterated all other cells. During the development of the culture adipocytes became differentiated from mononuclear cells and frequently were located within spherical multicellular aggregates (spheroids). Functional assessments were employed to investigate whether the multinucleated cells generated in this way, represented osteoclast-like cells, or alternatively, were related to macrophage polykarya as found in foreign body granulomata in vivo. Neither resorption pits on sperm whale dentine slivers (diagnostic of osteoclasts), nor formation of granulomata in vitro, were observed. We believe that the present results indicate that the multinucleated cells generated from canine bone marrow mononuclear precursors in vitro, merit designation as osteoclast-like cells. Definitive characterisation however, must await further functional assessments of hormone responsiveness. PMID- 1499050 TI - In-vitro effects of angiotensin II on steroid production by hamster ovarian follicles and on ultrastructure of the theca interna. AB - Angiotensin II (AII) is present in the mammalian ovary and has been correlated with atresia in follicles. Since the theca interna may be one site at which atresia is initiated, we wished to determine whether AII exerts an effect on theca interna from explanted ovarian follicles of hamsters. Hamsters were sacrified on the morning of proestrus, and ovaries were removed. Preovulatory follicles were excised from the ovaries, and cultured with one of the following components: medium alone (control); medium plus AII (1 x 10(-6) M); the AII receptor antagonist [Sar1, Ile8] AII (1 x 10(-4) M); or AII plus antagonist. After 72 h, the follicles were processed for transmission electron microscopy (to determine quantities of theca interna organelles involved in the steroid synthetic pathway) or for protein determination (to normalize steroid production rates). The incubation medium was drawn off and analyzed by radioimmunoassay for progesterone, androstenedione, or estradiol-17 beta. There was a significant positive correlation (r = 0.92, P less than 0.01) between follicular androstenedione secretion and area comprising theca interna smooth endoplasmic reticulum. In the theca interna, AII induced a two-fold and 1.6-fold increase in lipid droplet number and area comprising smooth endoplasmic reticulum, respectively (P less than 0.05). Excess antagonist negated the increase in cell organelles and also reduced androstenedione secretion compared with AII alone (P less than 0.05). Most importantly, AII significantly augmented the ratio of androstenedione:estradiol-17 beta secretion by 44% over that of control. The ultrastructural changes observed in this study and the increase in the androstenedione:estradiol-17 beta production ratio are consistent with atresia like changes in ovarian follicles.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1499051 TI - Occurrence of unusual heterogeneous lipid-containing granule-storing cells in the main excretory duct epithelium of the male mouse submandibular gland. AB - The fine structure of the main excretory duct epithelium of the male mouse submandibular glands was investigated by scanning and transmission electron microscopy. Three principal cell-types were observed: type I and II, and basal cells. This epithelium was characterized by the presence of intercellular canaliculi. Type-I cells were the most numerous. They had an abundance of mitochondria, well-developed Golgi apparatus, a few electron-lucent lipid containing granules and poorly developed basal infoldings. These cells were also characterized by many glycogen granules throughout the cytoplasm and abundant smooth endoplasmic reticulum in the apical cytoplasm. Type-II cells were the second most numerous. Their most characteristic feature was the presence of abundant heterogeneous lipid-containing granules having acid phosphatase activity at the periphery. They were concentrated in the infra- and supra-nuclear cytoplasm. The granules may be derived from mitochondrial transformation and seem to be a special kind of secondary autolysosome. Type-II cells also contained abundant mitochondria throughout the cytoplasm, much smooth endoplasmic reticulum in the apical cytoplasm, a well developed Golgi apparatus adjacent to the heterogeneous lipid-containing granules and no basal infoldings. Basal cells were situated adjacent to the basal lamina. They had a large nucleus and the cytoplasm was filled with glycogen granules. PMID- 1499053 TI - Embryonic origin and development of the corpuscles of Stannius in chum salmon (Oncorhynchus keta). AB - An immunocytochemical technique was used to follow the embryological origin and development of the corpuscles of Stannius (CS) in the chum salmon, Oncorhynchus keta. Stanniocalcin immunoreactive (ir-) cells can be observed as early as 13 days before hatching. The ir-CS cells appear in clusters of variable size in close association with nephric ducts. In addition, individual ir-cells also occur at this stage among epithelial cells of the nephric ducts. These individual cells may give rise to clusters which subsequently increase in size, the largest reaching 100 microns in diameter by the time of hatching. During this period, dispersed CS cells become evident and develop into secondary clusters in the vicinity of the primary clusters. These clusters appear to fuse to form larger clusters with a lobular structure. Transfer of the larvae (20 days after hatching) from fresh water to 50% seawater, accelerates the development of the CS tissue, suggesting an important role of the CS in seawater adaptation. PMID- 1499052 TI - The relationship between odontoblasts and pulp capillaries in the process of enamel- and cementum-related dentin formation in rat incisors. AB - The relationship between odontoblasts and pulp capillaries in the process of dentinogenesis was studied in rat lower incisors, both on the labial and lingual sides, using light and transmission electron microscopy. The odontoblasts showed remarkable differences from the apical to the incisal end. Near the apical end of the tooth, "immature odontoblasts", which were thought to be involved in the formation of the mantle dentin, were arranged in a single layer, and continuous capillaries were located just beneath the odontoblasts. In the middle of the tooth, "mature odontoblasts" with highly developed cell organelles and notable processes formed a pseudostratified layer; fenestrated capillaries were found between these cells close to the predentin. The height of the odontoblast layer and the rate of dentin deposition on the labial (enamel-related) side was significantly greater than that on the lingual (cementum-related) side. Near the incisal end, cementum-related odontoblasts gradually decreased in height and number to become "post-odontoblasts" that produced atubular dentin; continuous capillaries were located subjacent to the post-odontoblasts. On the labial (enamel-related) side, however, odontoblasts retained their pseudostratification; fenestrated capillaries were still observed in the odontoblast layer. No atubular dentin was formed on the labial side. PMID- 1499054 TI - Forebrain specialization and the olfactory system in anseriform birds. An architectonic and tracing study. AB - In anseriform birds the mediodorsal part of the rostral forebrain is covered by a corticoid (= layered) structure, establishing a unique feature of this avian group since in other birds the non-cortical accessory or dorsal hyperstriatum occupies the corresponding surface area of the hemisphere. The efferents of the olfactory bulb are shown to reach this region, which thus can be identified as a heavily enlarged retrobulbar area. The large expansion of this olfactory representation may indicate an important biological function. In comparison to the mammalian olfactory system the three stratified olfactory projection centers of birds should be regarded as retrobulbar, prepiriform and periamygdalar regions. PMID- 1499055 TI - Localization of Lom-AG-myotropin I-like substances in the male reproductive and nervous tissue of the locust, Locusta migratoria. AB - Lom-AG myotropin I (Lom-AG-MTI) was the first peptide to be isolated from the male accessory reproductive glands of the locust, Locust migratoria. It shows no sequence similarity to any of the peptides identified from vertebrate or invertebrate tissues. A polyclonal antiserum was used to localize Lom-AG-MTI-like material in the male reproductive system and nervous system of the locust. Immunoreactivity was found in two of the hyaline gland tubules. In the brain, cell bodies were detected in the photo- and deuterocerebrum as well as the frontal ganglion. Nerve fibers were stained in the neuropils of the brain and throughout the labial nerves into the recurrent nerve. Thoracic and last abdominal ganglia contained neurons which could be stained with Lom-AG-MTI antiserum. The pronounced reactivity in the central nervous system suggests a possible neuroregulatory function of the peptide. PMID- 1499056 TI - Virtual real-time digital processing of hemodynamic data. AB - At present, the majority of cardiac catheterization laboratories acquire and store hemodynamic data in analog form. To examine the possibility of performing complex analysis of digital data during the catheterization procedure, we examined whether virtual real-time digital (fast Fourier) analysis improves the accuracy of clinical data. We compared digital filtering of fluid manometry during the right heart catheterization with 10-Hz and 250-Hz analog filters. Using the simultaneously acquired micromanometry as the "gold standard," we found that analog filtering is associated with a greater error and time delay than digital filtering. This study demonstrates that digital hemodynamic data analysis performed during cardiac catheterization can improve the quality of data obtained during right heart catheterization, with the results available within seconds. More extensive use of computers in the cardiac catheterization laboratory may be useful for both clinical and research purposes. PMID- 1499057 TI - Intracoronary thrombolysis followed by directional atherectomy: a combined approach for thrombotic vein graft lesions considered unsuitable for angioplasty. AB - Eccentric complex vein graft lesions with abundant luminal thrombus have been generally considered unfavorable for balloon angioplasty. We present 3 patients in whom such lesions were successfully treated by a combined approach: intracoronary urokinase (1 million units over 1 hr) administered in the catheterization laboratory followed by directional atherectomy of the residual lesions in 2 separate procedures; with the patients maintained on heparin infusion between the 2 stages. No distal embolizations were encountered. Two of the 3 patients developed a groin hematoma without vascular compromise. This combined approach may prove to be an attractive alternative to reoperation in select patients with unfavorable vein graft lesions. PMID- 1499058 TI - Coronary arteriovenous fistula presenting as congestive heart failure. AB - Coronary arteriovenous fistulae are rare, but can be of hemodynamic significance. We report a circumflex-coronary sinus fistula in an elderly man which was associated with a loud continuous murmur and congestive heart failure. Noninvasive evaluation, including transesophageal echocardiography and magnetic resonance imaging, suggested the diagnosis. Angiographic diagnosis of concomitant atherosclerotic coronary disease may be difficult, and can require postoperative study. PMID- 1499059 TI - Origin of all three coronary arteries from separate ostia in the right sinus of Valsalva: a rarely reported coronary artery anomaly. AB - Anomalous origin of the circumflex and left anterior descending coronary arteries from separate ostia in the right sinus of Valsalva is a rarely reported phenomenon. Few clinical details concerning patients with this anomaly are available in the literature. Angiographic and clinical data in an adult patient with this finding are reported here. PMID- 1499060 TI - Left ventricular diverticulum: case report and review of the literature. AB - We describe two patients with left ventricular diverticula which were seen during routine left ventriculography. The diverticula were probably incidental findings and asymptomatic. A review of the literature to determine associated cardiac and extra-cardiac abnormalities and related morbidity and mortality with emphasis of potential treatment strategies is presented. PMID- 1499061 TI - Interpretation of cardiac pathophysiology from pressure waveform analysis: pericardial compressive hemodynamics, Part II. AB - Constrictive physiology characteristically alters atrial and ventricular waveforms. Normal pressure and flow responses to inspiration are blocked or reversed. The impairment of early diastolic filling is the common feature of restrictive myocardial, as well as diseased pericardial, processes. Low pressure tamponade can limit cardiac output, but may be difficult to detect by clinical signs alone. Examination of the pressure waveforms may provide clues to the diagnosis of constrictive physiology in these patients. PMID- 1499062 TI - A Doppler guided retrograde catheterization system. AB - A Doppler guided retrograde catheterization system was developed to accurately catheterize the aortic root and left ventricular chamber without X-ray. This system consists of a 20 MHz, 0.076 mm thick x 1.016 mm diameter pulsed Doppler crystal integrated into the tip of a 100 cm multipurpose triple lumen catheter. Two lumens (0.61 mm) are used for electrodes; a third lumen (1.245 mm) may be used for guidewire and pressure determination; and the system is attached to a flow velocimeter. In an aortic arch flow model, the principles of Doppler signal guidance were confirmed with flow toward the catheter tip demonstrating positive signals and flow away from the catheter tip demonstrating negative signals. The magnitude and polarity (direction) of the detected phasic and mean velocities were utilized to guide catheterization in six dogs. Using the reversal of Doppler signal polarity to indicate branch entry and manipulating the catheter so as to maintain maximal positive axial velocity, the Doppler catheter was successfully advanced from the femoral artery to the aortic valve. Branches detected by the Doppler system were confirmed by fluoroscopy. The aortic valve was audible when approached and the left ventricular chamber was recognized by its characteristic pressure waveform. The Doppler guided retrograde catheterization system offers new technology to perform left heart catheterization without X-ray and may prove useful in a variety of settings including the development of invasive ultrasonic diagnostic and therapeutic technology. PMID- 1499063 TI - A prospective randomized study of 4.1 French catheters utilizing the percutaneous right brachial approach for the diagnosis of coronary artery disease. AB - To determine the utility of 4.1 French (F) catheters in diagnosing coronary artery disease, 50 patients were randomized to 4.1F Multipurpose or Judkins catheters utilizing the percutaneous right brachial approach. The randomized 4.1F tip shape catheter completed the procedure in 40% of the patients, and overall the 4.1F catheters completed the catheterization in 72% of the cases. With excessive or prolonged manipulation, the catheters were noted to kink and soften and required replacement for a catheter of similar or larger size. In 28% of the cases, larger F sizes (5F and 6F) were used to complete the procedure. There was 1 (2%) procedural complication. The total procedural success (accounting for all F sizes) without clinical complication was 98%. There was no difference between the 4.1F Judkins or Multipurpose catheter shapes for coronary arteriography by either qualitative or quantitative angiographic analysis. Left ventricular opacification was improved with the 4.1F Pigtail vs. the 4.1 Multipurpose by qualitative angiographic analysis. When the 4.1F angiograms were compared by quantitative angiography in blinded, but not randomized fashion to angiograms performed with 6F Judkins catheters, there was improved opacification of the LAD and diastolic frame of the left ventriculogram with the larger catheter. This difference was not noted with qualitative angiography. This study indicates that 4.1F catheters can be utilized from the right brachial approach for the diagnosis of coronary artery disease, thus avoiding the need for supine bedrest associated with routine femoral artery catheterization while maintaining diagnostic accuracy. PMID- 1499064 TI - Coronary angioplasty using an over-the-wire balloon catheter through a new 6 French guiding catheter. AB - A new 6 French (F) guiding catheter with a large, teflon-coated internal lumen (4.2F) was developed, permitting use of the standard ultralow profile (less than 3F) over-the-wire system. This small coronary angioplasty system (6F-PTCA) was evaluated in 48 lesions in 45 of 137 patients (33%) who underwent coronary angioplasty between September 1990 and January 1991. The mean age was 64 years (range 49 to 82); 37 (82%) were male. The procedure was via the brachial artery in 28 patients (62%). The overall primary success rate was 96%. It was 100% via the brachial artery and 90% via the femoral artery. There were no major complications. The puncture compression time with the 6F-PTCA via the brachial artery and via the femoral and with 8F-PTCA via the femoral was 3.8, 9.6, and 16.9 hr, respectively (P less than 0.001), although the procedure time of the 6F PTCA via brachial and via femoral and of the 8F-PTCA was not significantly different. The mean hospital stay was 3.1, 4.5, and 5.5 days, respectively (P less than 0.01). A small hematoma occurred in 2 patients (4.4%) after the 6F-PTCA and in 3 (3.3%) after 8F-PTCA, and a large hematoma (greater than 5 cm) was noted in 7 patients (7.6%) after 8F-PTCA. These results indicate that coronary angioplasty using the over-the-wire system through the new 6F guiding catheter is technically feasible. Moreover, this approach, especially when advanced via the brachial artery, could shorten the hemostasis time and facilitate early ambulation. PMID- 1499065 TI - The mobile catheterization laboratory: should we pick it up and move it? The trustees of the Society for Cardiac Angiography and Interventions. PMID- 1499066 TI - Mobile cardiac catheterization laboratories. Society for Cardiac Angiography and Interventions Laboratory Performance Standards Committee. AB - The Society of Cardiac Angiography and interventions proposed guidelines for the establishment of mobile cardiac catheterization laboratories. These laboratories should be established only in areas with genuine need, preferably as determined by an objective medical authority. Safety of the patient should be of paramount importance and specifications as to the selection of patients, transportation of patients with complications, the relationship to a tertiary care center, and quality assurance mechanisms are all addressed. PMID- 1499068 TI - Clinical evaluation of the temporomandibular joint. PMID- 1499067 TI - Aortic dissection as complication of percutaneous transluminal coronary angioplasty. AB - We report two cases of aortic dissection during coronary angioplasty with a disparate evolution that was due to the different location of the entry port of the dissection. Aortic dissection occurring during coronary angioplasty may be self-limiting, but it may also be life-threatening and may call for urgent surgical repair. PMID- 1499069 TI - Medicare: what it covers. PMID- 1499070 TI - [The roles of T cells in experimental crescentic glomerulonephritis]. AB - A crescentic glomerulonephritis (GN) model was induced by intravenous injection of rabbit anti-mouse glomerular basement membrane (GBM) antiserum and lipopolysaccharide (LPS) in BALB/c mice, heterozygous mice and nude mice respectively, in order to detect the T-cells effects on the development of crescentic GN. The immunofluorescence and morphological changes of glomeruli in different groups of animals were compared. Intense fluorescence (4+) of rabbit IgG could be found along the GBM in liner pattern in all the animals. Intense (3(+)-4+) mouse IgG was also found along the GBM in liner pattern in the normal and heterozygous mice, but could not be identified in the nude mice. The normal mice developed typical crescentic GN, characterized by serious degeneration and destruction of GBM, fibrin deposition and crescents formation, 3-6 weeks after the injection. The heterozygous mice only developed mild proliferation of the mesangial cells in the glomeruli but there was no glomerular lesion detected in the nude mice. It suggests that the glomerular immune damage requires the participation of functional T-cell. PMID- 1499071 TI - [Study of deposition and translocation of mineral dust in lungs of tin miners in Yunnan by X-ray microanalysis]. AB - Histochemistry, SEM-EDX and X-ray fluorescence analysis were applied to detect the distribution of iron, arsenic and other related elements in the pulmonary tissues of tin miners in Yunnan. Lesions obtained in human beings could be reproduced in rats subjected to intratracheal injection of arsenic containing ore dust, which was prepared in order to study the deposition, dissociation and release of inhaled less-soluble arsenic containing ors dust in the lungs and the process of development of different ferruginous bodies. Data obtained in the pulmonary tissues provided also the evidence about the role of arsenic as the etiological factor of lung carcinoma in the tin miners of Yunnan province. PMID- 1499072 TI - [Pathological study on 10 cases of inflammatory pseudotumour of the liver]. AB - Histopathological changes of 10 cases of resected inflammatory pseudotumour of liver were observed. These cases were considered to be the primary liver carcinomas or malignant tumours clinically. Morphologically, the inflammatory pseudotumour of liver exhibited varied histological features, including plasma cell granuloma, xanthogranuloma, fibrous proliferation, endophlebitis, necrosis etc. All these cases showed the characteristics of an inflammatory proliferative mass. The causes and the diagnosis criteria of inflammatory pseudotumours of liver were briefly discussed. PMID- 1499073 TI - [Extracellular matrix degradative enzymes and neoplasm invasiveness and metastasis]. PMID- 1499074 TI - [Effect of high density lipoprotein (HDL) on the clearance of intracellular lipids with special reference to the co-effect of nifedipine]. AB - More than 90% of peritoneal macrophages collected from the diet-induced hyperlipidemic rabbits were noticed to be loaded with abundant lipids, and were morphologically similar to the foamy cells infiltrating in the atheromatous lesion. Data of this experiment showed that HDL could promote the clearance rate of intracellular cholesterol efflux and this effect could be strengthened in the progress of time that HDL could transport more than 30% of the accumulated lipids from the cultured cells in 96 hours. Data also indicated that nifedipine was able to promote the hydrolysis of cholesteryl esters in the cultured cells. Addition of nifedipine to the culture media originally containing only HDL promoted the ability of foamy cells in excreting intracellular cholesterol via a hitherto unknown mechanism. This study indicated that nifedipine enhanced the cholesterol efflux mediated by HDL. PMID- 1499075 TI - [The antitumor effects of tumor-infiltrating lymphocytes (TIL) being proliferated in vitro]. AB - Tumor-infiltrating lymphocytes (TIL) were isolated from 19 solid tumors by means of in vitro digestion and discontinuous density gradient centrifugation. The average amount of TIL harvested from one gram of tumor tissue was 1.3 x 10(6). A four-week long term cultivation procedure was performed in 8 of the 19 specimens with rIL-2, and the number of TIL had then been expanded for 30 to 150 times more. Phenotypic analysis showed that most of TILs obtained were OKT3+ lymphocytes, and the ratio of OKT4+ and OKT8+ was decreased coincidently during the cultivation in vitro. The experiment showed that TILs exhibited stronger anti autologous tumor effects than that to the allogeneic tumors through both in vitro and in vivo studies. PMID- 1499076 TI - [RNA-RNA in situ hybridization for the study of expression of the GST-P, c-myc and H-ras-1 genes in a malignant liver cell line, HL-178]. AB - RNA-RNA in situ hybridization was applied in order to analyze the expression of GST-P, c-myc and H-ras-1 genes in a human malignant liver cell line, HL-178. The results showed presence of high expression of both GST-P and c-myc. Some parameters of in situ hybridization technique involved in this experiment were discussed. PMID- 1499077 TI - [Dynamic changes of fibronectin, DNA and morphology of the nuclei of experimental hepatoma in rats]. AB - The dynamic changes of fibronectin (FN) content and nuclear features (DNA content, morphological parameters) during the development of hepatoma induced by 3'-Me-DAB were studied via computer-assisted image analysis. The results showed that the amount of FN decreased progressively and even disappeared completely during hepatocarcinogenesis. The difference between distinctive foci or nodules was highly significant (P less than 0.0001) and the DNA content was also increased coincidently during the same process. PMID- 1499078 TI - [Study of the infiltrating lymphocyte subsets and transferrin receptor in gastric and colorectal carcinomas]. AB - Infiltrating mononuclear cell (MNC) subsets and transferrin receptor (TfR) expression at the localized lesions were studied in 28 cases of gastric carcinoma and 36 cases of colorectal carcinoma by immunohistochemical technique by using a panel of monoclonal antibodies. The results showed that the percentage of T4+ cells in the infiltrating MNCs decreased while that of T8+ cells increased relatively and the T4/T8 ratios declined along with the progression of the tumor. The TfR positive rates in gastric and colorectal carcinomas were 73.08% and 100% respectively. The expressing intensity of TfR in the tumors correlated with the density of local infiltrating MNC subsets. These findings indicated that the local immune response against tumor moves toward a tendency of developing a deeper inhibitory effect during the tumor progression. PMID- 1499079 TI - [Thickness of the media of pulmonary trunk in children with mountain sickness]. AB - Thickness of the media of pulmonary trunks from 58 children with mountain sickness were measured with micrometer. The results showed that the thickness of the media were increased coincidently with the increase of age, and PT/AT ratio. The pattern of the elastic laminae was in accordance with that of the aorta in the same group. The authors consider that these changes in mountain sickness are due to pulmonary hypertension development. PMID- 1499080 TI - Phenotypic expression of carcinogen-initiated epidermal cells to tumor cells by 12-O-tetradecanoylphorbol-13-acetate in a manner dependent on 3T3 fibroblast derived humoral factor(s). AB - Primary cultured newborn mouse epidermal cells cultured in the low Ca2+ (0.02 mM) medium showed typical basal cell morphology and proliferated as a monolayer. A stepwise increase in medium Ca2+ concentration induced terminal differentiation of epidermal cells. In the case of epidermal cells obtained from newborn mice transplacentally initiated with 7,12-dimethylbenz[a]anthracene (DMBA) or epidermal cells initiated in vitro by DMBA, a small number of rapidly growing cellular foci with epidermal morphology appeared and proliferated when the medium Ca2+ concentration was raised. Without increasing Ca2+ concentration, such foci never appeared. However, the Ca2+ concentration of the extracellular milieu of basal epidermal cells is known to be very low in in vivo epidermis. Under the low Ca2+ conditions, 12-O-tetradecanoylphorbol-13-acetate (TPA), a most potent skin tumor promoter, never induced rapidly growing cellular foci. When the initiated epidermal cells were co-cultured with 3T3 fibroblasts but without direct cell-to cell contact, TPA induced rapidly growing cellular foci even under the low Ca2+ condition. Without initiation, such cellular foci hardly appeared. 3T3 fibroblasts induced only a very small number of cellular foci in the absence of TPA. Co-culture with mouse peritoneal macrophages was not effective in inducing such cellular foci, indicating that the effect is 3T3 fibroblast specific. The conditioned medium of 3T3 fibroblasts was also capable of inducing such cellular foci. Three of these rapidly growing cellular foci were cloned and designated as WYF-30, WYF-31 and WYF-32 respectively. All of these three cell lines grew rapidly in the normal (1.8 mM) Ca2+ medium, indicating that these cell lines were resistant to Ca(2+)-induced differentiation. In the low Ca2+ medium, the growth of these three cell lines was stimulated by TPA. All three cell lines formed colonies in soft agar. The number of colonies formed under the normal Ca2+ condition was larger than that formed under the low Ca2+ condition. Under the low Ca2+ condition, the colony formation of each cell line was augmented by TPA. All the cell lines formed tumors in nude mice. These results indicate that TPA induces phenotypic expression of dormant initiated cells to tumor cells in a manner dependent on 3T3 fibroblast-derived humoral factor(s). PMID- 1499081 TI - Sulfotransferase-mediated DNA binding of N-hydroxyarylamines(amide) in liver cytosols from human and experimental animals. AB - Characteristics of cytosolic sulfotransferase-mediated binding of carcinogenic N hydroxyarylamines(amide) have been investigated and compared among experimental animal species and humans in vitro. Human cytosols exhibited significant sulfating activities towards 2-hydroxyamino-6-methyldipyrido[1,2-a:3',2' d]imidazole (N-hydroxy-Glu-P-1), N-hydroxy-2-aminofluorene (N-hydroxy-AAF) and N hydroxy-2-acetylaminofluorene (N-hydroxy-AAF), but had no detectable activity toward 2-hydroxyamino-3-methyl-imidazo[4,5-f]quinoline (N-hydroxy-IQ). Although the extent of the covalent binding of these N-hydroxyarylamines(amide) differed significantly among individuals, clear correlations were observed among the sulfation of N-hydroxyarylamines (amide) and also with p-nitrophenol sulfation. Hepatic cytosols from mouse, rat, guinea-pig, hamster, rabbit, dog and monkey also mediated the binding of N-hydroxy-Glu-P-1, N-hydroxy-AF and N-hydroxy-AAF, while only rat cytosols showed detectable DNA binding of N-hydroxy-IQ. Among the species examined, rat showed the highest capability for activating these N hydroxyarylamines(amides). Significant sex-related differences were detected in rat, dog and monkey for all substrates examined, except N-hydroxy-IQ. Clear correlations were observed in the animal species between N hydroxyarylamines(amide), but not with p-nitrophenol. Using an ion-exchange chromatographic system, sulfating activity of p-nitrophenol in human livers was separated into two fractions and the PAPS-dependent DNA binding of N-hydroxy-AF was supported mainly by the later fraction. On Western blots, an immunoreactive protein was detected in these fractions using an antibody raised against rat hepatic N-hydroxy-AAF sulfotransferase. The band was also detected in human hepatic cytosols with considerable individual variation in their amounts. These results indicate the involvement of a closely related form(s) of sulfotransferase in the PAPS-mediated activation of N-hydroxyarylamines(amide) in human as well as in the experimental animal species. PMID- 1499082 TI - Increase in estrogen receptor levels in MNU-induced thyroid tumors in LE rats. AB - Estrogen receptor (ER) levels were evaluated in thyroid tumors induced by N methyl-N-nitrosourea (MNU) and low iodine diet (LID) or propylthiouracil (PTU) in intact and estrogen (E2) loaded Long-Evans (LE) rats. MNU at 40 mg/kg body wt was injected in 50 day-old LE rats of both sexes. The animals were killed 17-22 weeks later and the thyroid tissues were subjected to ER assay. In LID-treated groups, cytosolic ER (cER) levels were 6.7 +/- 5.8 (fmol/mg protein, mean +/- SE) in females and 0.7 +/- 1.4 in males, E2 increased the ER levels. In E2-loaded LID groups, cER levels were 12.9 +/- 3.7 in females and 1.7 +/- 1.7 in males. PTU treatment produced almost comparable ER levels as LID treatment. PTU treatment as well as LID treatment increased the serum TSH levels with E2 treatment producing additional elevation. In evaluating ER levels by histological type of thyroid tumors, the level in cER plus nER showed the lowest value of 6 +/- 6.4 (fmol/mg DNA, mean +/- SE) in hyperplasia, followed by 129 +/- 52.3 in adenoma and 289 +/- 51.7 in carcinoma. The rates of BrdU incorporation in thyroid follicles indicated higher proliferation activity in the area of adenoma and carcinoma rather than in the hyperplastic area. These data suggested that E2 treatment increases the ER levels in MNU and LID/PTU-induced thyroid tumors. The level of ER was correlated to the histological type of thyroid tumors. PMID- 1499083 TI - Ascorbate is the principal reductant of chromium(VI) in rat lung ultrafiltrates and cytosols, and mediates chromium-DNA binding in vitro. AB - Chromium(VI) reductase activity was measured in ultrafiltrates of rat lung after various pretreatments in vitro at 37 degrees C and pH 7.0. Pretreatment of ultrafiltrates with L-ascorbate oxidase (EC 1.10.3.3), which specifically eliminated ascorbate, blocked approximately 95% of chromium(VI) reductase activity in ultrafiltrates. Preincubation of ultrafiltrates with heat-denatured ascorbate oxidase or the sulfhydryl-blocking agent N-ethylmaleimide (NEM) had no significant effect on Cr(VI) reductase activity. In rat lung cytosols, L ascorbate oxidase blocked approximately 95% and NEM blocked approximately 15% of Cr(VI) reductase activity. The extent of inhibition of Cr(VI) reductase activity in cytosols by L-ascorbate oxidase was significantly decreased to approximately 75% after addition of 1.0 mM NADPH. When Cr(VI) was incubated with salmon sperm nuclei suspended in rat lung cytosol for 15 min, Cr became bound to nuclear DNA. This Cr-DNA binding was completely inhibited by preincubation of rat lung cytosols with L-ascorbate oxidase and inhibited approximately 60% by preincubation with NEM. Taken together these data suggest that ascorbate and/or ascorbate-dependent factors are the principal reductants of Cr(VI) in both ultrafiltrates and cytosols prepared from rat lung and ascorbate-dependent metabolism of Cr(VI) results in Cr binding to nuclear DNA in vitro. Although sulfhydryl-containing factors and NADPH-dependent factors only make a minor contribution to Cr(VI) reduction in rat lung cytosols, sulfhydryls may be significantly involved in the binding of Cr to nuclear DNA. PMID- 1499084 TI - Increased exposure to dietary amines and nitrate in a population at high risk of oesophageal and gastric cancer in Kashmir (India). AB - Analytical data on aliphatic amines and nitrate from the most commonly used fresh and sun-dried vegetables, red chillies and a widely consumed beverage, salted tea, are presented from a high risk area for oesophageal and gastric cancer in Kashmir. Exposure estimates for the adult population show that high consumption of boiled Brassica vegetables leads to a high nitrate intake of 237 mg/day. The frequent consumption of hot salted tea is shown to result in exceptionally high exposure to methylamine (1200 micrograms/day), ethylamine (14,320 micrograms/day), dimethylamine (150 micrograms/day) and diethylamine (400 micrograms/day). The indiscriminate use of red chillies in the area leads to exposure to dimethylamine (280 micrograms/day), pyrrolidine (517 micrograms/day) and methylbenzylamine (40 micrograms/day). This is to our knowledge the first report where a chronic exposure to methylbenzylamine has been shown in a population at high risk of oesophageal cancer. PMID- 1499085 TI - Modulation of carcinogenicity in 1,2,3,4-tetrahydro-7,12- dimethylbenz[a]anthracene (THDMBA) by fluorine substitution: crystal structures of the 5- and 6-fluoro regioisomers. AB - 1,2,3,4-Tetrahydro-7,12-dimethylbenz[a]anthracene (THDMBA) is an animal carcinogen which lacks an aromatic bay-region and shows promise as a model to investigate non-classical mechanisms of carcinogenesis. The fluorine-substituted derivatives at positions 5 and 6 on the B-ring exhibit a striking range of oncogenic potential wherein the 6F-THDMBA is twice as potent as the parent carcinogen, but the 5F-THDMBA is virtually inactive. To study structure reactivity relationships for these fluorine regioisomers, we have determined the three-dimensional structures of the compounds by single-crystal X-ray diffraction. These crystal structures are the first such to be reported for any monofluoro anthracene (or pyrene) derivative. The partially-reduced A-ring exists in both enantiomeric half-chair conformers in the crystalline state, and the compounds have quasi-planar anthracene ring systems which exhibit a right-handed twist in the 'beta'-conformer, with the expected opposite twist in the other. A complete analysis of bond lengths, bond angles and torsion angles is presented. Preliminary electrostatic potentials have been derived from the X-ray data sets, and the results indicate significant differences in potential between 5F- and 6F THDMBA at positions near the partially reduced bay region. Such results are likely to be of importance in the understanding of metabolic activation to reactive intermediates capable of bonding covalently to DNA. PMID- 1499086 TI - Bioactivation of aflatoxin B1 in the bovine olfactory mucosa: DNA binding, mutagenicity and induction of sister chromatid exchanges. AB - Nasal olfactory tumours occur in cattle in relatively high frequencies in several developing countries. Since affected animals sometimes show signs of severe aflatoxicosis, a role of aflatoxin B1 (AFB1) in tumorigenesis can be proposed. The results of the present study show that microsomal preparations of the bovine olfactory mucosa have a much higher ability than liver microsomes to induce covalent binding of AFB1 to calf thymus DNA and to microsomal proteins. The major DNA adduct formed was 8,9-dihydro-8-(N7-guanyl)-9-hydroxy-aflatoxin B1. Incubations of microsomal preparations of the bovine nasal olfactory mucosa with glutathione (GSH) and cytosolic fractions of the nasal mucosa resulted in decreased AFB1 DNA binding. A more pronounced decrease was observed when cytosolic fractions of mouse liver were added to the incubations. Mouse liver is known to contain a glutathione-S-transferase with a high ability to scavenge the reactive AFB1-epoxide via conjugation to GSH. Our results indicate that AFB1-GSH conjugation occurs less efficiently in the bovine nasal olfactory mucosa than in the mouse liver. Supernatant preparations (9000 g) of the bovine nasal olfactory mucosa incubated with AFB1 were shown to have the capacity to induce a strong genotoxic response both as regards induction of gene mutations in Salmonella typhimurium TA100 and the induction of sister chromatid exchanges in Chinese hamster ovary cells. Preparations of the bovine liver (9000 g) has a much lower ability to induce these effects. The results of the present study show that the bovine nasal olfactory mucosa has a high AFB1-bioactivating capacity, which can be related to the potent DNA damaging and mutagenic effects observed. It is considered that our results support the assumption that AFB1 plays a role in the aetiology of nasal tumours in cattle. PMID- 1499087 TI - Transplacental carcinogenic effects of nickel(II) acetate in the renal cortex, renal pelvis and adenohypophysis in F344/NCr rats. AB - Nickel(II) acetate (NiAcet), a soluble nickel salt known to be an effective initiator of renal epithelial tumors in adult rats, was studied for possible transplacental carcinogenicity. Pregnant F344/NCr rats were given NiAcet i.p. either once a day on day 17 (90 mumol/kg body wt; group 1) or twice on days 16 and 18 of gestation (45 mumol/kg body wt/day; group 2). Offspring of these rats were further subdivided into groups 1A and B and 2A and B, respectively. Groups 1A and 2A received ordinary tap water while groups 1B and 2B received drinking water containing 500 p.p.m. sodium barbital (NaBB) during weeks 4-85 of age. Renal cortical epithelial and renal pelvic transitional epithelial tumors occurred in male offspring given NiAcet prenatally followed by NaBB postnatally (group 1B, 15 tumors in 8/15 rats; group 2B, 10 tumors in 7/15), but not in male offspring given NiAcet only (0/32) or in controls given prenatal sodium acetate (NaAcet) only (0/15) and rarely in males given NaAcet followed by the promoter NaBB (1/15). No renal tumors occurred in females. Pituitary tumor incidence was significantly higher in offspring of both sexes given NiAcet prenatally (NaAcet controls, 4/31, both sexes combined; group 1A, 14/33, P = 0.012; group 2A, 14/31, P = 0.008). Pituitary tumors appeared much earlier in rats given NiAcet prenatally, with or without postnatal NaBB, and often were malignant by cytologic and histologic criteria including pleomorphism and invasion of adjacent structures, unlike the well-differentiated adenomas that occurred less frequently in untreated rats. These results are the first evidence that Ni(II) is a potent transplacental initiator of epithelial tumors in fetal rat kidney and a complete transplacental carcinogen for rat pituitary. PMID- 1499088 TI - Point mutation analysis of ras genes in spontaneous and chemically induced C57Bl/10J mouse liver tumours. AB - The high incidence and profile of ras gene mutations reported in spontaneous and chemically induced liver tumours of the B6C3F1 mouse provides a potential means of determining in vivo genotoxicity and its relevance to carcinogenicity. We analysed spontaneous and chemically induced [with 4-amino-biphenyl (ABP), 2 acetylaminofluorene (AAF) and diethylnitrosamine (DEN)] hepatocellular tumours of the C57Bl/10J mouse for H-ras, K-ras and N-ras gene mutations to see if mutational analysis of the ras genes could be useful for such a determination in this strain. Regions of DNA spanning codons 12, 13 and 61 of the ras genes were amplified from formalin fixed liver tumour sections using the polymerase chain reaction. Mutations were detected using allele specific oligonucleotide probing and confirmed by sequencing. We have found that there are few ras mutations in either spontaneous or chemically induced liver tumours in the C57Bl/10J mouse. Out of 25 spontaneous tumours two contained an A to T transversion and one contained an A to G transition in base 2 of H-ras codon 61 and two contained a G to A transition in base 2 of K-ras codon 13 (the K-ras mutations were only faintly detectable and may be present in a subpopulation of the tumour cells). In the case of the 18 ABP induced tumours one contained a C to A transversion in base 1 of H-ras codon 61, and one contained an A to T transversion in base 2 of H ras codon 61 and one contained a G to C transversion in base 1 of K-ras codon 13. One C to A transversion in base 1 of H-ras codon 61 was detected out of eight AAF induced tumours. Of the 25 DEN induced tumours, one contained an A to G transition and one contained an A to C transversion in base 2 of H-ras codon 61. The data indicate that at least in hepatocellular tumours of the C57Bl/10J strain and using chronic dosing regimes the ras genes do not represent markers for in vivo genotoxic activity. PMID- 1499089 TI - Study of interaction of styrene oxide with angiotensin by mass spectrometry. AB - The present study describes how mass spectrometry was extensively applied to the characterization and quantification of modified amino acids within the polypeptide chain of Angiotensin I, chosen as model substrate, combining the use of fast atom bombardment mass spectrometry with gas chromatography--mass spectrometry. The reaction products after in vitro incubation of Angiotensin I with styrene oxide, a well known carcinogen, under different conditions, have been characterized: a prominent reactivity of several potential nucleophilic sites of Angiotensin I was shown, including two histidine residues and a tyrosine residue; it is worth noting that it has never been stated that tyrosine is highly reactive with styrene oxide. The results obtained demonstrate the usefulness of mass spectrometry for the structural determination of chemically modified amino acids in peptides and proteins, and the presence of a reliable relationship between reaction conditions and the production of alkylated amino acids. This characterization procedure offers the possibility of identifying reactive sites following exposure to unknown alkylating agents. PMID- 1499090 TI - Strategies for advancement of short-term mutagenicity tests: on the optimal ionic strength for the liver microsomal assay. AB - The aim of this work was to optimize the ionic strength (tau) in the liver microsomal assay (LMA) in performing short-term genotoxicity tests. tau optimization would increase the sensitivity (i.e. decrease false negatives) and at the same time increase the specificity (decrease false positives). Such optimization depends upon the relative activities and stabilities of the liver polysubstrate cytochrome P450- and FAD-containing monooxygenase-dependent metabolizing enzymes present in the incubation mixtures. With regard to phase-I pathway, the expression of various P450-like activities (IA1, IA2, IIB1, IIE1, IIIA P450 classes) and thiobenzamide s-oxidase (as FAD-MFO marker), were examined in terms of their exact incubation conditions for the LMA during a period of preincubation (1 h) over the tau range 0.06-1.40. As a comparison with the phase II pathway, the behaviour of glutathione S-transferases (total and pi class), glutathione S-epoxide transferase, epoxide hydrolase and UDP-glucuronosyl transferase were studied. Lipid peroxidation (LP) was also determined. Experiments were performed on S9 fractions derived from sodium phenobarbital, beta-naphthoflavone, isosafrol, ethanol and pregnenolone 16-alpha carbonitrile super-induced mouse liver. The maximal value of the mean specific activity (Asp), up to a 46% increase, was found at tau = 0.864 for oxidative reactions considered. On the contrary, a slight modulation of Asp for post-oxidative reactions was seen. LP was not changed appreciably by varying tau. In vitro DNA binding of the well-known premutagenic agent [14C]dimethylnitrosamine ([14C]DMNA), mediated by mouse hepatic microsomal enzymes, showed a significant increase of specific activity at tau = 0.864 (2.25-fold) compared to the usual tau (0.06) used. Additional confirmation of these results stems from mutagenesis experiments using DMNA on the diploid D7 strain of Saccharomyces cerevisiae as a biological test system. Indeed, a significant enhancement of mitotic gene conversion (up to 1.8-fold), mitotic crossing-over (2.6-fold) and reverse point mutation (2.6-fold) frequencies was achieved at tau = 0.86 compared to tau = 0.06 (traditional). These data show that tau = 0.86 can provide more convenient conditions for in vitro bioactivation (as exemplified by an increased Asp phase I/Asp phase-II ratio), as well as DNA binding and genotoxic response. PMID- 1499091 TI - Kinetics and enzyme involvement in the metabolism of 4-(methylnitrosamino)-1-(3 pyridyl)-1-butanone (NNK) in microsomes of rat lung and nasal mucosa. AB - The rat lung and nasal cavity are two target organs for carcinogenesis by 4 (methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK). In order to characterize further the enzymes involved in the bioactivation of NNK, detailed kinetic and inhibitory studies were conducted with rat lung and nasal mucosa microsomes, and the results were compared with previous studies. The enzymes in rat lung microsomes catalyzed the alpha-hydroxylation, pyridine N-oxidation and carbonyl reduction of NNK. The apparent Km for the formation of the NNK-derived keto aldehyde, NNK-N-oxide, the NNK-derived keto alcohol and 4-(methylnitrosamino)-1 (3-pyridyl)-1-butanol were 28.8, 10.4, 7.0 and 178.1 microM respectively. In rat nasal microsomes, alpha-hydroxylation was the predominant pathway and the rate was approximately 200 times higher than that in lung microsomes. The apparent Kms for keto aldehyde and keto alcohol formation in rat nasal microsomes were 9.6 and 10.1 microM respectively. The cytochrome P450 inhibitors metyrapone and carbon monoxide markedly inhibited the metabolism of NNK in both rat lung and nasal microsomes. In rat lung microsomes, alpha-naphthoflavone and monospecific antibodies against P450s 1A2, 2A1 and 2B1 inhibited the formation of keto aldehyde by 39, 46, 64 and 23% respectively. In rat nasal microsomes, alpha naphthoflavone and antibodies against P450s 1A2, 2A1 and 3A inhibited the metabolism of NNK by 80, 35, 20 and 14% respectively. The results indicate that cytochromes P450 play a major role in the metabolic activation of NNK in rat lung and nasal microsomes, and that there are tissue-related differences in NNK metabolism. PMID- 1499092 TI - Mutagenesis by (+)-anti-B[a]P-N2-Gua, the major adduct of activated benzo[a]pyrene, when studied in an Escherichia coli plasmid using site-directed methods. AB - The suspected major mutagenic adduct of benzo[a]pyrene, (+)-anti-B[a]P-N2-Gua, is built into the unique PstI recognition site of the Escherichia coli plasmid, pUC19, in order to study its mutagenic potential. The adduct can either be at G437, which is replicated during leading strand DNA synthesis, or at G438, which is replicated during lagging strand DNA synthesis. The DNA strand complementary to the strand containing the (+)-anti-B[a]P-N2-Gua adduct is saturated with UV lesions to minimize its potential to generate progeny. Although all in-frame mutations could have been detected, a G437----T transversion mutation is virtually exclusively obtained at a frequency of approximately 0.04% per adduct following transformation into Uvr+ E. coli when SOS is not induced, and approximately 0.18% when SOS is induced. The mutation frequency of the adduct in a Uvr- background is estimated to be approximately 0.2% when SOS is not induced, and approximately 0.9% when SOS is induced. The absence of G438----T mutations is rationalized. G----T mutations from (+)-anti-B[a]P-N2-Gua are compared to the mutational specificity of the ultimate mutagenic form of activated benzo[a]pyrene. PMID- 1499093 TI - Dose-dependent formation of preneoplastic foci and DNA adducts in rat liver with 2-amino-3-methyl-9H-pyrido[2,3-b]indole (MeA alpha C) and 2-amino-1-methyl-6 phenylimidazo[4,5-b]pyridine (PhIP). AB - Dose responses to two heterocyclic amines, 2-amino-3-methyl-9H-pyrido[2,3 b]indole (MeA alpha C) and 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP), in induction of glutathione S-transferase placental form positive liver cell foci (GST-P+ foci) and DNA adduct formation in the liver were examined in male F344 rats. Beginning 2 weeks after a single diethylnitrosamine (DEN) injection (200 mg/kg, i.p.), rats received MeA alpha C or PhIP in the diet at various doses for 6 weeks. All rats were subjected to two-thirds partial hepatectomy (PH) 1 weeks after the test agents were added to the diet and were killed 8 weeks after DEN initiation. MeA alpha C (100, 200, 400 and 800 p.p.m.) significantly increased numbers and areas of GST-P+ foci over control levels in all dose groups with a clear dose-response. In contrast, PhIP (50, 100, 200 and 400 p.p.m.) only equivocally increased foci development in the highest dose group and rather was associated with decrease in the lower dose groups. DNA adduct formation assessed by 32P-postlabeling demonstrated a dose-dependent increase with both chemicals, the levels being much higher with MeA alpha C. Thus, two highly mutagenic heterocyclic amines that are produced in broiled foodstuffs exerted different influence on GST-P+ foci development and DNA adduct formation; these findings are consistent with liver carcinogenicity in rats and/or mice. PMID- 1499094 TI - The genotoxicity of UVA irradiation in Drosophila melanogaster and the synergistic action of 8-methoxypsoralen and UVA. AB - To study the genotoxicity of near-ultraviolet light (UVA) on a whole body, Drosophila melanogaster larvae were irradiated with UVA and the emerging flies were examined for the mutant wing spot formation. The genotoxicity of UVA was also assayed with the in vivo DNA-repair test using males with repair-deficiency at the mei-9 and mei-41 locus and the matching repair-proficient females. Third instar larvae were placed in a plastic Petri dish, which was covered with soft glass, and irradiated with black light at 4-5 W/m2. This irradiation resulted in an increase in mutant wing-hair spots. After a 15 h irradiation (approximately 240 kJ/m2), the mutant clone frequencies found in the adult flies (spots/wing) were: 1.68 for the small single spots, 0.38 for the large single spots and 0.11 for the twin spots, while at zero time they were 0.68, 0.06 and 0.02 respectively. On the other hand, the UVA irradiation was negative in the in vivo DNA-repair test, indicating that the UVA-induced DNA lesion may not be subject to repair by the mei-9 and mei-41 functions. The presence of 8-methoxypsoralen (8 MOP) during the irradiation remarkably enhanced somatic mutations, and showed a strong DNA-damaging effect in the repair test. For example, a 15 h UVA irradiation with 26.7 microM 8-MOP resulted in a 14-fold increase in the number of twin spots per wing as compared with the frequency obtained on treatment with UVA alone. Treatment of the larvae with 8-MOP alone gave no mutant clones or DNA damage. A high frequency in twin spot formation was also observed in this UVA + 8 MOP treatment, indicating that extensive chromosomal recombinations took place in the somatic cells. PMID- 1499095 TI - Response of the ke test to NCI/NTP-screened chemicals. II. Genotoxic carcinogens and non-genotoxic non-carcinogens. AB - A physico-chemical carcinogen-screening test was used to measure the rate constants of electron attachment, kes, of 105 chemicals that had been screened in long-term rodent bioassays and short-term in vitro tests by the NCI/NTP. In the ke test, a pulse-conductivity technique is used to generate and monitor the decay of excess electrons that serve as nucleophilic surrogates for the target tissue of rodents. Of the 61 chemicals that had been found to be rodent carcinogens as well as Salmonella mutagens, 36 yield kes that are equal to or greater than the diffusion-controlled ke of carbon tetrachloride and are considered to be positive ke test responses. In contrast, 29 of the remaining 44 chemicals that are putative non-carcinogens and non-mutagens yield kes that are negative ke test responses. These results are combined with the ke responses of 46 non-mutagenic carcinogens and 20 mutagenic non-carcinogens that were reported earlier and are evaluated to determine the degree to which the measure of electron-accepting capacity that ke provides complements or overlaps the electrophilicity or DNA reactivity of chemicals that is indicated by positive mutagenicity responses in the Ames Salmonella tester strains or by positive structural alerts, S/As, of the chemicals. The combined ke test results indicate that the overall predictivity of the ke test is comparable to and complements the Ames Salmonella test and S/As in identifying rodent carcinogens. Moreover, the electrons serve as non-discriminate nucleophilic targets for both genotoxic and non-genotoxic electron-accepting molecules and appear to attach with equal efficiency to carcinogens that are active in various tissues of rodents. This property of excess electrons suggests that the predictivity of the ke test could be enhanced by combining the measured ke with an appropriate lipophilicity or pharmacokinetic parameter. A pre-chemical electron-transfer step that had been proposed to precede chemical interactions between the carcinogen and target tissue is discussed in light of recent developments in electron-donor/-acceptor chemistry and in the application of structure--activity relationships to identify carcinogens. PMID- 1499096 TI - Modulation by glutathione of DNA strand breaks induced by 4-(methylnitrosamino)-1 (3-pyridyl)-1-butanone and its aldehyde metabolites in rat hepatocytes. AB - Activation of the tobacco carcinogen 4-(methylnitrosamino)-1-(3-pyridyl)-1 butanone (NNK) produced methylating species and two aldehydes: formaldehyde and 4 oxo-4-(3-pyridyl)-butanal (OPB). We investigated the modulation by glutathione of single-strand breaks (SSB) generated by N-methyl-N-nitrosourea (MNU) and the two aldehydes. Hepatocytes were simultaneously exposed to 0.2 mM MNU and to 0-2.00 mM formaldehyde or OPB for 4 h. Both aldehydes induced SSB in a dose-dependent manner. Formaldehyde and OPB exerted a synergistic effect on the formation of DNA SSB by MNU. It is postulated that both aldehydes interfere with DNA repair processes and thus increase the genotoxic effect of DNA methylating species. We investigated whether glutathione (GSH) could protect DNA from NNK-derived intermediates. Formaldehyde (2 mM) and OPB (2 mM) decreased intracellular GSH contents to 60 and 86% of control respectively. DL-Buthionine-[S,R]-sulfoximine (BSO) treatment reduced the GSH contents of hepatocytes to 19% of control but did not reduce the content of cytochrome P450 nor the metabolism of NNK. The frequency of DNA SSB induced by NNK, formaldehyde or OPB was significantly higher in GSH-depleted hepatocytes. GSH repletion with GSH monoethyl ester returned NNK induced SSB to its initial frequency. OPB but not NNK nor formaldehyde induced double-strand breaks. We conclude that OPB and formaldehyde inhibit the repair of DNA damage induced by methylating species and that GSH reduces the level of DNA damage induced by NNK-derived reactive metabolites. PMID- 1499097 TI - Sequence specificity of DNA repair by Escherichia coli Fpg protein. AB - The sequence specificity of guanine methylation in DNA by N-methyl-N-nitrosourea and the subsequent repair of ring-opened N7-methylguanine was studied using oligonucleotides of defined sequence. It was found that the methylation of TAGGGGCCCCTA was less than 2-fold greater than that occurring in TAGAGATCTCTA or TATGTGCACATA and 6-fold greater than in TACGCGCGCGTA. This is consistent with the concept that guanine methylation is least when the 5' preceding base is a pyrimidine and greatest when the 5' base is another guanine. These dodecamers were used to study repair by the Escherichia coli Fpg protein (formamidopyrimidine-DNA glycosylase) after the 7-methyl-guanine present in them was converted to the ring-opened form by alkaline treatment. The repair of ring opened 7-methylguanine was much faster in self-complementary double-stranded 12mer substrates and was twice as rapid at 37 degrees C in TAGGGGCCCCTA compared with TACGCGCGCGTA. However, at 15 degrees C, the relative rates were reversed since TACGCGCGCGTA was repaired at the same rate as at 37 degrees C, whereas the repair of TAGGGGCCCCTA was much slower at 15 degrees C. The repair of TAGGGGCCCCTA at 37 degrees C was also much faster than the repair of TAGAGATCTCTA and was slightly more rapid than repair of TATGTGCACATA. Ligation of the dodecamer substrates to form 24mers or 36mers slightly reduced the initial rates of repair but did not abolish these differences. These results indicate that under physiological conditions, the Fpg protein is more active against adducts in guanine-rich regions and such regions may be the most likely sites of adduct formation at the N7-position of guanine which can then give rise to derivatives attacked by this enzyme. PMID- 1499098 TI - DNA adduct formation by o-phenylphenol metabolite in vivo and in vitro. AB - [U-14C]o-Phenylphenol (OPP) was found to bind covalently to calf thymus DNA during a 60 min incubation in the presence of microsomes, but not in their absence, indicating that metabolic conversion of the parent compound, OPP, to an activated form is essential. Postlabeling analysis with bladder DNA of rats fed a diet containing 2% OPP for 13 weeks revealed one major adduct on TLC. In an in vitro postlabeling experiment with calf thymus DNA, both of the major metabolites of OPP, phenylhydroquinone (PHQ) and phenylbenzoquinone (PBQ), formed adducts, but no adducts were observed with OPP. The chemical structure responsible for adduct formation is thought to be the PHQ semiquinone radical intermediate formed during interconversion between PHQ and PBQ. When the oligonucleotides, pd(A)12 18, pd(C)12-18, pd(G)12-18 and pd(T)12-18, were used in vitro, only pd(G)12-18 gave TLC-detectable adducts on treatment with PHQ and PBQ. The covalent binding appears to be rather specific to guanine residues. These results suggest that covalent binding of the OPP metabolite is one of the underlying events in OPP induced carcinogenesis in rats. PMID- 1499099 TI - Storage phosphor imaging technique for detection and quantitation of DNA adducts measured by the 32P-postlabeling assay. AB - The 32P-postlabeling method has found wide application as a sensitive technique for detecting the presence of a broad range of bulky aromatic compounds covalently bound to DNA. In this method, the modified DNA is enzymatically degraded to 3'-mononucleotides and labeled with [32P]-phosphate at the 5' position using [gamma-32P]ATP and T4 polynucleotide kinase. The 32P-labeled DNA digest is then chromatographed in two dimensions on polyethyleneimine - cellulose thin-layer plates. Screen-enhanced autoradiography is used to locate the presence of the radiolabeled adducts on the chromatogram, and the radioactive areas are generally excised and quantitated by liquid scintillation spectrometry. However, on a chromatogram with multiple adducts, it can be difficult to quantitative partially resolved adducts and evaluated background radioactivity levels. We have evaluated the use of storage phosphor imaging techniques to quantitate and map the radioactivity on chromatograms generated by the 32P-postlabeling method. The results showed that storage phosphor imaging was approximately 10 times more sensitive than screen-enhanced autoradiography at -80 degrees C for the detection of 32P, exhibits a greater linear range of response, has a resolution that compares favorably to film and has a lower background than does liquid scintillation spectrometry. Further, the generation of a digitized record of the distribution and intensity of radioactivity allows for computer-assisted assessment of adduct profiles and can facilitate quantitation of individual adducts and radioactive zones comprised of multiple overlapping adducts in complex chromatograms. Additionally, the permanent record created by the imaging technology permits facile retrospective analysis of samples, whereas with autoradiography and liquid scintillation spectrometry reanalysis of a replicate sample is required. PMID- 1499100 TI - Association between expression of transforming growth factor-alpha and progression of hepatocellular foci to neoplasms. AB - Hepatocarcinogenesis was initiated in rats with a single dose of either of two chemical mutagens--benzo[a]pyrene diolepoxide I and methyl(acetoxymethyl)nitrosamine--administered 15 h after partial hepatectomy. The development of hepatocellular foci and neoplasms was then promoted with dietary phenobarbital given for 45 or 62 weeks. Formalin-fixed tissue specimens that contained hepatic neoplasms and altered hepatocellular foci were screened for expression of the oncodevelopmental marker glutathione-S-transferase (placental form) (GSTP) and transforming growth factor-alpha (TGF-alpha) using immunohistochemistry. All (100%) hepatocellular carcinomas expressed both GSTP and TGF-alpha, as did most hepatocellular adenomas (greater than 80%). However, quantitative stereologic analysis of treated and control livers revealed that GSTP-positive foci were 10-30 times more frequent than TGF-alpha-positive foci. Foci with homogeneous expression of GSTP generally displayed heterogeneous expression of TGF-alpha with reaction product most prominent at their peripheries. Less frequently homogeneous TGF-alpha-positive foci were seen within GSTP-positive foci. The average volumes of those GSTP-positive foci that also expressed TGF-alpha were significantly greater than those of the entire sets of GSTP-positive foci. These results suggest that expression of TGF-alpha may distinguish a subset of GSTP-positive foci that have a growth advantage and increased probability of progression to neoplasia. PMID- 1499101 TI - A simple, sensitive assay to detect DNA-protein crosslinks in intact cells and in vivo. AB - Addition of potassium chloride to sodium dodecyl sulfate (SDS) resulted in the formation of an insoluble precipitate that was easily recovered by low-speed centrifugation. Since SDS tightly binds to proteins but not DNA, all proteins and detergent-resistant DNA--protein complexes were also effectively co-precipitated in the presence of potassium--SDS leaving free DNA in the supernatant. The amount of SDS-precipitable DNA represented a measure of DNA--protein crosslinks. We have adapted this method for determining DNA--protein crosslinks formed in cells following their exposure in culture or in vivo to crosslinking agents such as chromate, cis-Pt(II) diammine dichloride and formaldehyde. The critical parameters for application of the K--SDS assay to cells were rigorously reproducible shearing of chromosomal DNA and effective washing steps. We have found that freeze-thawing SDS lysed cells followed by vortexing and repeated resuspensions of the precipitate by pipeting resulted in a low background and high reproducibility of the assay. The method detected in a dose-dependent manner DNA--protein crosslinks induced in CHO cells by chromate, cis-platinum and formaldehyde, with sensitivity similar to the alkaline elution procedure. The K- SDS assay was also successfully utilized to determine DNA--protein crosslinks in rat and mouse white blood cells exposed in vivo to chromate. Its sensitivity and simplicity in sample handling and DNA--protein complex isolation potential allows wide application of the assay to measure formation of DNA--protein crosslinks. The ease of recovery of DNA--protein complexes allows for a more thorough investigation of this lesion. PMID- 1499102 TI - Protection against benzo[a]pyrene- and N-nitrosodiethylamine-induced lung and forestomach tumorigenesis in A/J mice by water extracts of green tea and licorice. PMID- 1499103 TI - Mechanical matching of the left ventricle with the arterial system in exercising dogs. AB - We investigated how changes in ventricular contractility and arterial properties associated with exercise influence the energy transmission from the left ventricle to the arterial system. On six chronically instrumented dogs preconditioned to run on a treadmill, we imposed exercise loads of various degrees by altering the speed and slope of the treadmill (up to 7 km/hr and 20% slope). We evaluated ventricular contractility by end-systolic elastance (Ees) and arterial properties in terms of the effective arterial elastance (Ea). Ea was estimated by the ratio of mean aortic pressure to stroke volume. With exercise, Ees significantly increased from 7.6 +/- 1.7 to 10.9 +/- 2.6 mm Hg/ml (p less than 0.005), and Ea tended to increase from 4.9 +/- 1.4 to 6.7 +/- 1.8 mm Hg/ml (p = 0.068), whereas the ratio of Ea to Ees remained fairly constant (from 0.69 +/- 0.26 to 0.63 +/- 0.21, NS). The mechanical optimality index, defined as the ratio of stroke work to its theoretically derived maximal value, was 0.93 +/- 0.07 at rest and 0.92 +/- 0.08 at peak exercise. Similarly, the metabolic optimality index, defined as the ratio of cardiac oxygen consumption to stroke work conversion efficiency and its theoretical maximal value, was 0.98 +/- 0.02 at rest and 0.99 +/- 0.01 at peak exercise (NS). We conclude that external work of the left ventricle of these dogs was at a near maximal level for a given preload during exercise as well as at rest without compromising the conversion efficiency of metabolic energy to stroke work. PMID- 1499104 TI - A model study of volume conductor effects on endocardial and intracavitary potentials. AB - An idealized mathematical model was developed to study the effects of variations in conductive and geometric parameters on measured endocardial and intracavitary potentials. The model consists of a spherical multielectrode probe located eccentrically within a system of concentric spheres that represent a blood cavity, myocardium, lung region, and surface muscle layer. Solutions were found for endocardial and intracavitary probe potentials produced by two different configurations of equivalent myocardial sources: 1) multiple activation wave fronts oriented radially, representing global fronts in the myocardium; and 2) pairs of equal and opposite dipoles on a line oriented tangentially to the endocardial surface, representing cardiac sources during early ectopic activation. It was found that the complexities of the cardiac source configurations are reflected in the endocardial potential but not in the associated probe potential, which exhibits a smoothed-out, low-amplitude distribution. In addition, probe potential depends on probe size and location within the cavity. Furthermore, endocardial and probe potentials are influenced by variations in the conductivity of different regions; an increase in blood conductivity results in a decrease in both endocardial and probe potential magnitudes produced by either type of cardiac sources, and an increase in myocardial conductivity results in an increase in both potential magnitudes, whereas an increase in lung conductivity results in an increase in the magnitude of the potential produced by radial sources but a small decrease in the magnitude of the potential produced by tangential sources. The effects of variations in skeletal muscle conductivity are negligible. The volume conductor effects of myocardial anisotropy (9:1 anisotropy ratio) are to attenuate both endocardial and probe potentials by as much as 60% and 71%, respectively, for radial sources and by 96% and 85%, respectively, for tangential sources. In conclusion, volume conductor influences should be considered in the interpretation of measured cavity potentials. Multiple myocardial events are resolved in endocardial potentials but not in potentials measured by an intracavitary multielectrode probe. This observation indicates that for the purpose of resolving cardiac activity, efforts should be directed at inverse reconstruction of endocardial potentials from potentials measured with an intracavitary probe. PMID- 1499105 TI - Superoxide dismutase enhances ischemia-induced reactive hyperemic flow and adenosine release in dogs. A role of 5'-nucleotidase activity. AB - To test the hypothesis that 5'-nucleotidase activity during ischemia is attenuated by oxygen-derived free radicals, we measured ischemia-induced reactive hyperemic flow, adenosine release, and 5'-nucleotidase activity in dogs (n = 62). A 1-minute occlusion of the coronary artery caused reactive hyperemic flow (307 +/- 5 versus 92 +/- 1 ml.100 g-1.min-1 at baseline) with increased release of adenosine (14.4 +/- 1.4 versus 0.4 +/- 0.1 nmol.100 g-1.min-1 at baseline). Superoxide dismutase augmented (p less than 0.001) both peak coronary blood flow (333 +/- 6 ml.100 g-1.min-1) and repayment (436 +/- 12 versus 320 +/- 7 ml/100 g in the untreated group). Adenosine release during reperfusion was augmented (22.7 +/- 1.9 nmol.100 g-1.min-1, p less than 0.001), and 8-phenyltheophylline completely abolished the enhanced reactive hyperemia. Enzymatic assay of 5' nucleotidase activity revealed that the administration of superoxide dismutase increases ecto-5'-nucleotidase activity in ischemic myocardium. When an inhibitor of ecto-5'-nucleotidase, alpha, beta-methyleneadenosine 5'-diphosphate, was administered, the effects of superoxide dismutase were completely abolished. Thus, we conclude that 1) the augmentation of reactive hyperemic flow caused by superoxide dismutase is attributed to the enhanced release of adenosine and 2) the enhanced release of adenosine over the untreated controls is attributed to the protection of ecto-5'-nucleotidase activity during ischemia. PMID- 1499106 TI - Heparin adheres to the damaged arterial wall and inhibits its thrombogenicity. AB - Heparin binds to thrombogenic extracellular matrices as well as to smooth muscle cells of the vascular wall in vitro. The inhibitory effects of heparin on thrombogenicity of the damaged arterial wall were examined in vivo using small mesenteric arteries of rats and a video recording system attached to a microscope. To induce thrombosis, we damaged the vessel wall over a short segment by compression and exposed the media to the blood stream. A platelet-rich thrombus enlarged gradually at the damaged site, occluded the vascular lumen for a short period, and then flowed away. Compression damage induced such thrombus formation several times. Heparin (500 units/ml) was given in three different ways: intravenous and intra-arterial administration (both 300 units/kg) and intraluminal application under stopped-flow conditions (less than 0.01 ml) for 1 2 minutes with subsequent draining out. Intravenous heparin significantly decreased both the total duration and the number of thrombotic occlusions, whereas intra-arterial heparin abolished thrombotic occlusion. Both routes of heparin administration similarly prolonged the blood coagulation time. Intraluminal application of heparin significantly inhibited subsequent thrombus formation after restoring the flow without changes in the blood coagulation time. After an intra-arterial administration or intraluminal application of fluorescein isothiocyanate-bound heparin, strong fluorescence was observed only at the damaged vascular segment. A heparin fraction with low affinity to antithrombin III or chondroitin sulfate A did not inhibit thrombosis. To clarify anticoagulant activity of vascular wall-bound heparin, damaged carotid arterial segments of rats were incubated (inside out) in platelet-poor plasma with thrombin, and fibrin clot formation around the segments with or without heparin binding was measured.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1499107 TI - Comprehensive model of transport and metabolism of adenosine and S adenosylhomocysteine in the guinea pig heart. AB - Regulation of blood flow and mitochondrial respiration in the heart would be clarified by improved knowledge of interstitial concentrations and cellular production rates of adenosine; however, these variables cannot be measured directly. To interpret indexes that are available, a comprehensive mathematical model was developed, based on a large body of experimental data. The model describes most of the important pathways of capillary-tissue transport and cellular metabolism of adenosine in the guinea pig heart. It includes capillary flow, solute transport between tissue regions, nonlinear enzyme kinetics for adenosine kinase and adenosine deaminase, and reversible biunireactant kinetics for S-adenosylhomocysteine hydrolase in cardiomyocytes and endothelial cells, intracellular production of adenosine via AMP hydrolysis and transmethylation, and extracellular production of adenosine. A single set of parameter values for the model was obtained in the first stage of the analysis by taking certain values directly from published sources, other values were subject to specific constraints, and other values were determined by parameter optimization. The effects of flow and endothelial metabolism on the relation between interstitial and venous adenosine concentrations were determined. The relation between myocardial adenosine production rate and S-adenosylhomocysteine accumulation in the presence of excess homocysteine was estimated. In the second stage of the analysis, the model was used to investigate the mechanism of myocardial adenosine production, without changing the parameter values. Cellular adenosine production rates were estimated by fitting measurements of venous adenosine release obtained during altered energetic conditions in experiments by different investigators. The original results showed a dissociation between measurements of cytosolic AMP concentrations and venous adenosine release. It is concluded that 1) it is essential to account for the effect of flow on interstitial and venous adenosine concentrations, since decreased flow may produce effects outwardly resembling inhibition of the enzyme 5'-nucleotidase, 2) adenosine concentrations in epicardial transudate are not in equilibrium with interstitial fluid, and 3) the rate of cellular adenosine production increases monotonically with free cytosolic concentrations of AMP during a variety of alterations in energy balance of the guinea pig heart. PMID- 1499108 TI - Relation of mitochondrial and cytosolic free calcium to cardiac myocyte recovery after exposure to anoxia. AB - Mitochondrial calcium overload has been suggested as a marker for irreversible injury in the ischemic heart. A new technique is used to measure dynamic changes in mitochondrial free calcium concentration ([Ca2+]m) in electrically stimulated (0.2 Hz) adult rat cardiac myocytes during exposure to anoxia and reoxygenation. Cells were incubated with indo-1 AM, which distributes in both the cytosol and mitochondria. After Mn2+ quenching of the cytosolic signal, cells were exposed to anoxia, and the residual fluorescence was monitored. [Ca2+]m averaged 94 +/- 3 nM (n = 16) at baseline, less than the baseline diastolic cytosolic free calcium concentration ([Ca2+]c, 124 +/- 4 nM, n = 12), which was measured in cells loaded with the pentapotassium salt of indo-1. [Ca2+]m and [Ca2+]c rose steadily only after the onset of ATP-depletion rigor contracture. At reoxygenation 35 minutes later, [Ca2+]c fell rapidly to preanoxic levels and then often showed a transient further rise. In contrast, [Ca2+]m showed only a slight transient fall and a secondary rise at reoxygenation. At reoxygenation, cells immediately either recovered, demonstrating partial relengthening and retaining their rectangular shape and response to stimulation, or they hypercontracted to rounded dysfunctional forms. Recovery occurred only in cells in which [Ca2+]m or [Ca2+]c remained below 250 nM before reoxygenation. Early during reoxygenation, [Ca2+]m remained higher in cells that hypercontracted (305 +/- 36 nM) than in cells that recovered (138 +/- 9 nM, p less than 0.05), whereas [Ca2+]c did not differ between the two groups (156 +/- 10 versus 128 +/- 10 nM, respectively; p = NS).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1499109 TI - Suppression of endothelin-1 secretion by lysophosphatidylcholine in oxidized low density lipoprotein in cultured vascular endothelial cells. AB - Oxidatively modified low density lipoprotein (oxidized LDL), an atherogenic lipoprotein that exists in the atherosclerotic arteries, has been shown to alter endothelial cell functions. In the present study, we examined the effects of oxidized LDL on the production of endothelin-1-like immunoreactivity (ET-1-LI) by the cultured vascular endothelial cells from porcine aorta and human umbilical vein. Incubation with oxidized LDL resulted in a dose-dependent suppression of ET 1-LI release by both endothelial cells. Oxidized LDL also inhibited thrombin mediated stimulation of ET-1-LI secretion. However, native LDL had no effects on ET-1-LI secretion. A lipid extract from oxidized LDL, but not from native LDL, inhibited ET-1-LI secretion, indicating that the lipid component of oxidized LDL was required for the inhibition of ET-1-LI secretion. Oxidative modification of LDL was associated with degradation of a substantial amount of phosphatidylcholine to lysophosphatidylcholine (LPC). Pretreatment with defatted albumin, which is an acceptor for hydrophilic lipids including LPC, reduced LPC concentration in oxidized LDL to that in native LDL and simultaneously prevented the inhibitory effects of oxidized LDL on ET-1-LI secretion. Incubation with synthetic LPC (palmitoyl), but not with synthetic phosphatidylcholine (dipalmitoyl), suppressed ET-1-LI secretion by the endothelial cells. No cell death was observed during the incubations as judged by the trypan blue exclusion test, and protein synthesis of the endothelial cells was not affected by lipids or lipoproteins at a concentration at which suppression of ET-1-LI was observed. We concluded that LPC in oxidized LDL causes suppression of ET-1-LI release, which may counteract the vasoconstrictive properties of atherosclerotic arteries. PMID- 1499110 TI - Differential effects of elevating [K]o on three transient outward potassium channels. Dependence on channel inactivation mechanisms. AB - We carried out a systematic study on the effects of elevating [K]o on the properties of a transient outward potassium channel encoded by a cardiac cDNA (RHK1) and compared them with those on two Shaker potassium channels (H-4 and H 37). The amino acid sequences of all three channels are known, and their structure-function relations have been partially characterized. All three channels were expressed in Xenopus oocytes and studied under double microelectrode voltage-clamp conditions. For all three channels, elevating [K]o caused an increase in the channels' chord conductances and a negative shift in the calculated activation curves. However, in other aspects of channel properties that are related to the channels' inactivation processes, there were differences in the changes induced by increasing [K]o: 1) Elevating [K]o caused a positive shift in the steady-state inactivation curves of RHK1 and H-4 but did not cause any shift in H-37. 2) Elevating [K]o slowed the time course of inactivation of H 37 but did not cause any significant changes in the time course of RHK1 or H-4. 3) Elevating [K]o accelerated the rate of recovery from inactivation of RHK1 and H-4 but slowed the recovery time course of H-37. Our experiments show that elevating [K]o can cause a wide range of effects on the transient outward potassium channels. Furthermore, raising [K]o induced similar changes in RHK1 and H-4 (inactivation mediated by an "N-type" mechanism) that were different from the changes in H-37 (inactivation mediated by a "C-type" mechanism). Therefore, our data suggest that part of the effects of elevating [K]o on channel properties may depend on the channel's inactivation mechanism. This hypothesis is supported by results from experiments studying the effects of elevating [K]o on a mutant RHK1 channel (RHK1 delta 3-25), which apparently lacks the N-type and C-type inactivation mechanisms. PMID- 1499111 TI - Correlation between [5-3H]glucose and [U-14C]deoxyglucose as markers of glycolysis in reperfused myocardium. AB - Studies were conducted in extracorporeally perfused, intact, working pig hearts to determine whether, in heart muscle, trace-labeled deoxyglucose serves as an accurate marker of glycolytic flux in reperfusion after exposures to mild to moderate regional ischemia. In the main study, two groups of hearts were compared, as distinguished by levels of glucose in the whole-blood perfusate (euglycemic hearts [group I], blood glucose of 7.4 +/- 0.2 mumol/ml, n = 7; hyperglycemic hearts [group II], blood glucose of 12.9 +/- 0.5 mumol/ml, n = 8). Both groups were subjected to a 60% reduction in anterior descending coronary flow for 30 minutes followed by reperfusion for 40 minutes. Modest and comparable regional mechanical stunning during reflow was noted in both groups. Glucose utilization, as estimated from the release of 3H2O from the steady-state infusion of [5-3H]glucose during aerobic perfusion, was modest but during reperfusion was noted to increase significantly above aerobic values in each of the two groups, with a doubling of rates in group II hearts compared with group I hearts (p less than 0.041 or p less than 0.090). Net lactate extraction was comparable in reflow in both groups, suggesting in this specific instance a preferential enhancement of glucose oxidation in hyperglycemic group II hearts. Shifts in accumulation of tissue radioactivity of [U-14C]2-deoxyglucose in reperfused myocardium were not able to track these trends. The variability of 14C-labeled radioactivity among animals was marked and essentially masked any ability to discern trends in glycolysis as described by tritiated glucose between the aerobic and reperfusion intervals. When the data were arrayed by linear regression analysis, the slopes derived from 14C-labeled deoxyglucose were either discordant or insensitive to those described by 3H-labeled glucose. Tissue glycogen levels were slow to recover in early reflow and at end reperfusion were still significantly depressed from aerobic levels. The present data indicate that coronary reperfusion and hyperglycemia have influence in determining glycolytic flux in myocardium. Labeled deoxyglucose, considered solely as a marker of exogenous glucose utilization, appears to be an insensitive agent in describing these events at conditions of relatively low glucose flux. PMID- 1499112 TI - Maturation of interdependence between extra-alveolar arteries and lung parenchyma in piglets. AB - Mechanical interdependence between intrapulmonary structures and parenchyma has not been studied previously in immature postnatal lungs. To study these interactions, lung elastic moduli were measured by pressure-volume and punch indentation studies in lobes excised from 3-day-old (n = 6), 1-month-old (n = 6), and 3-month-old (n = 7) piglets. After extra-alveolar arteries were filled with a radiopaque fluid silicone compound, transpulmonary pressure and arterial pressure were varied independently as the lobar vein was occluded. Arterial diameters and lengths were measured from radiographs. Behavior of 3-month-old lungs was consistent with previous studies of adult lungs, but results were unique in 3-day old lungs. That is, during stepwise deflation of the immature lungs 1) intravascular pressures fell when arteries were occluded experimentally, 2) arteries increased their diameters when kept at a constant intravascular pressure, and 3) arterial lengths decreased by less than 3%. Behavior of 1-month old lungs was intermediate. A previous continuum mechanics analysis of pressure diameter behavior was modified to account for compression by alveolar pressure as vascular diameters increase. It was concluded that 1) radial and axial dimensions of extra-alveolar arteries are virtually independent of parenchymal expansion in newborn piglet lungs and 2) periarterial interstitial pressures increase as these lungs are inflated. Our interpretation of these findings is that a mechanical association of the arteries to the parenchyma occurs gradually with postnatal maturation. PMID- 1499113 TI - Extracellular and intracellular actions of adenosine and related compounds in the reperfused rat intestine. AB - By using pharmacological tools, the biological actions of adenosine (ADO) were manipulated in rat intestine that had been rendered ischemic for 5 or 15 minutes and reperfused for 1 or 24 hours. With 100 microM ADO topically administered for 30 minutes after ischemia and then washed out, intestinal arteriolar blood flow (BF) and tissue ATP were restored to preocclusion levels, and histological damage was minimal after 1 hour of reperfusion. For comparison, with vehicle treatment after ischemia, BF was reduced by 50%, tissue ATP was reduced by 50%, myeloperoxidase levels in the intestine and lung were increased at least twofold, and mucosal villi were shortened and thickened after 1 hour of reperfusion. Furthermore, with vehicle treatment, both baseline BF and reactivity to endothelium-dependent (acetylcholine) and endothelium-independent (2 chloroadenosine) vasodilators were significantly depressed after 24 hours of reperfusion. In contrast, with ADO, baseline BF remained near normal, and vascular reactivity to 2-chloroadenosine and acetylcholine was preserved after 24 hours. The salutary effect of ADO on BF was reduced by simultaneous application of the antagonist 8-phenyltheophylline or the cellular uptake inhibitor dipyridamole. The nonmetabolized agonist 2-chloroadenosine, the purine precursor aminoimidazole carboxamide riboside, or dipyridamole alone all had favorable effects relative to the vehicle, but all were less potent than ADO. The conclusions are as follows: 1) Endogenous ADO modulates the inflammatory response evoked by intestinal reperfusion because aminoimidazole carboxamide riboside or dipyridamole, which increases its availability, generally had favorable effects, whereas 8-phenyltheophylline tended to have opposite effects. 2) Exogenous ADO arrests most of the inflammatory changes associated with reperfusion by mechanisms that include both extracellular (e.g., receptor-mediated vasodilation and granulocyte inhibition) and intracellular (e.g., restoration of ATP) actions. 3) The effectiveness of ADO-related compounds even when administered after ischemia attests to the practicality of salvaging ischemic bowel, at least in some conditions. PMID- 1499114 TI - Functional expression of an inactivating potassium channel cloned from human heart. AB - Recently a putative K+ channel with homology to the Shaker family of potassium channels has been cloned from human ventricular myocardium. However, proof that the cDNA encodes a K+ channel requires appropriate translation and expression of a functional ion-selective channel. Therefore, expression of this putative human K+ channel DNA was attempted by cytoplasmic injections of in vitro transcribed cRNA into Xenopus laevis oocytes and screening by two-electrode voltage-clamp methods. This resulted in expression of voltage-gated channels that rapidly inactivated (time constant of inactivation, 47.6 +/- 3.6 msec; 0 mV; n = 10) and were at least 50 times more selective for K+ than Na+ (Na+/K+ permeability ratio of 0.02). The channels showed voltage-dependent activation (half-maximal voltage, -34 +/- 0.7 mV; n = 5), and 50% of the channels were inactivated within 2 seconds when the membrane potential was clamped near -60 mV (half-maximal voltage, -62 +/ 7 mV; n = 10). The expressed protein resulted in a K+ current that had many properties similar to the 4-aminopyridine-sensitive calcium-insensitive component of the cardiac transient outward current that is observed in native cardiac myocytes and thus may serve as one molecular substrate for this current. PMID- 1499116 TI - Professional malaise--what can we do about it? PMID- 1499115 TI - Voltage-dependent gating and single-channel conductance of adult mammalian atrial gap junctions. AB - In the heart, the rapid propagation and synchronization of action potentials necessary for a normal heart rhythm and an effective cardiac output are mediated by specialized ionic channels that link adjacent cells and are known collectively as gap junctions. Cardiac gap junctions are gated by various physiological and pharmacological agents, but the role of voltage in their gating is unclear. Whereas embryonic or neonatal ventricular cells have voltage-gated gap junctions, adult cells are reported to have only voltage-independent gap junctions. We studied the voltage dependence of adult rat atrial gap junctions by individually voltage clamping each cell of a connected cell pair and controlling the transjunctional voltage (Vj), measuring transjunctional current (Ij), and calculating junctional conductance (gj). Two distinct populations of cell pairs were observed: highly coupled pairs with the peak gjs ranging from 3.4 to 40 nS and weakly coupled pairs with the peak gjs ranging from 0.3 to 2.0 nS. gj was dependent on Vj, and Ij decayed exponentially, with the time constants being voltage dependent. Voltage dependence was most apparent when cells were poorly coupled. The gj did not decrease to zero. The normalized conductance--Vj plot was fit with a two-state Boltzmann model as a first approximation, resulting in a half-inactivation potential and gating charge of 42.5 mV and 1.14 eV, respectively, for the weakly coupled cell pairs. For highly coupled cell pairs, the half-inactivation potential shifted to 53.3 mV. Single gap junctional channels had a gj of 36.2 +/- 7.6 pS (range, 27-49 pS), which was Vj independent.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1499117 TI - Keratoconus associated with ectodermal and mesodermal anomalies. PMID- 1499118 TI - Evaluation of tear protein deposits on contact lenses from patients with and without giant papillary conjunctivitis. AB - Giant papillary conjunctivitis (GPC) associated with contact lens wear is believed to result from an irritative or allergic response to accumulated lens surface deposits. In a masked study, contact lenses worn short-term (2 weeks or less) or long-term (2-12 months), and obtained from patients with and without active GPC, were examined for deposited proteins: IgA, IgE, IgG, IgM, lactoferrin, and lysozyme. Using immunohistochemical methods lenses were separately graded on a 4+ scale for extent of protein coverage. All lenses showed substantial deposits (averaging 50-75% lens coverage) of the normal tear proteins, with the exception of IgE which averaged less than 25% lens coverage; maximum protein deposition was apparent on lenses worn for only 3 days. Both symptomatic and asymptomatic persons deposited similar amounts of the common tear proteins on their contact lenses, with the exception of IgM. A statistically significant increase in IgM deposition was found when the short-term GPC lenses were compared to short-term asymptomatic lenses. Our data suggest that the development of GPC does not depend on amount of deposition of the normal tear proteins IgA, IgG, IgE, lactoferrin or lysozyme. Differences observed in IgM deposition may reflect an immune response in GPC. PMID- 1499119 TI - Residual hydrogen peroxide as a function of platinum disc age. AB - Recently there has been considerable attention given to the possible deleterious effects of residual hydrogen peroxide on both the cornea and the crystalline lens of the eye. We measured residual hydrogen peroxide levels of the AOSept disinfection system at regular intervals over a 4 month period. By 1 month the residual hydrogen peroxide level was 21 ppm +/- 9.4 (mean +/- standard deviation); at the end of 2 months it was 36 ppm +/- 17.6. At 3 months, when disc replacement is recommended, the residual hydrogen peroxide level was 43 ppm +/- 4.7 (range: 17-98 ppm). At 4 months the residual hydrogen peroxide level rose to a mean of 48 ppm +/- 18.2. The increase in measured residual hydrogen peroxide between month 1 and each successive month was found to be statistically significant. However, these levels failed to induce an increase in symptomatology or slit lamp findings. As determined by scanning electron microscopy there was an erosion of the platinum coating with time that appeared to coincide with the measured residual peroxide level. Cultures of randomly selected platinum discs at the end of 4 months failed to reveal more than isolated positive findings of Staphylococcus epidermidis. While an increase in residual peroxide with time may lead to greater disinfecting capabilities of this system, the possibility of corneal damage as a direct result of high peroxide levels is of concern. PMID- 1499120 TI - A critical evaluation of the Multi-item Microbial Challenge Test in ophthalmic disinfectant testing. AB - The Multi-item Microbial Challenge Test (MIMCT) is a stringent, carrier assay of the disinfecting efficacy of a contact lens care regimen. The test involves four steps: 1) in vitro contamination of contact lenses in the presence of organic load; 2) cleansing the contact lens by mechanical rubbing and subsequent rinsing; 3) disinfection of the cleansed lens; and 4) assaying the contact lens and the disinfecting solution for viable microorganisms. The variability of the individual steps was evaluated in this study by the Contributions of Elements protocol. The efficacy of the cleansing step, while reputed to be highly variable, was found to be reproducible and dependent upon the formulation under test. A contact lens disinfecting regimen must reduce the level of contaminants to approximately 10(-4) CFU/lens to enjoy a 95% chance of passing the MIMCT. This reflects a 10-log unit reduction from the initial inoculum of approximately 10(6) CFU/lens. The stringency of the MIMCT depends on the ability of the recovery system to allow the growth of low numbers of residual challenge microorganisms in the presence of the disinfecting solution. Neutralizers included in the recovery system to inhibit the disinfectant are therefore critically important to the stringency of the assay. The design of experiments to evaluate neutralizers specifically for the MIMCT is discussed with suggestions for an improved procedure. PMID- 1499121 TI - Contrast sensitivity measurements with the Echelon diffractive bifocal contact lens as compared to bifocal spectacles. AB - We examined the contrast sensitivity function of presbyopic subjects wearing the Hydron Echelon diffractive bifocal contact lens. Contrast sensitivity with the Echelon lens was compared to contrast sensitivity with bifocal spectacle correction. Each eye was tested for near and distance vision with the Echelon contact lens and with spectacle correction. Most subjects achieved a visual acuity of 20/20 with the Echelon lens; however, on average, contrast sensitivity was found to be significantly decreased with the contact lens as compared to spectacles for both distance and near vision. The largest decrease in contrast sensitivity was seen for mid-range spatial frequencies (4 to 16 cycles/degree). Although most subjects experienced a significant decrease in contrast sensitivity, two experienced only small decreases with the Echelon lens. Only one subject who met entry criteria reported that vision was as good with the Echelon lens as with spectacles. The decreased contrast sensitivity may result from contact lens decentration as well as inherent optical characteristics of the Echelon lens. PMID- 1499122 TI - Giant papillary conjunctivitis and meibomian gland dysfunction blepharitis. AB - In this prospective pilot study we saw 42 consecutive giant papillary conjunctivitis (GPC) patients (80 eyes), all of whom were found to have some meibomian gland dysfunction blepharitis. Severity of GPC at presentation correlated with severity of meibomian gland dysfunction blepharitis (Kendall's tau b averaged 0.246 across the adjusted statistical analyses). Thirty-two patients (63 eyes) were refit after treating meibomian gland dysfunction blepharitis. Twenty-eight of these patients (55 eyes; 87%) continue to wear contact lenses, maintaining an improvement in GPC (mean follow-up 21 months; range 11-36 months). We hypothesize that meibomian gland dysfunction blepharitis may play a role in the pathogenesis of GPC and suggest that a large, controlled, multi-observer study be performed to further investigate this possible association. PMID- 1499123 TI - Fitting the SoftPerm contact lens after keratoplasty. AB - We fit 22 eyes (20 patients) with the SoftPerm lens following keratoplasty when the potential acuity meter test exceeded the best corrected spectacle refraction. Fourteen eyes had more than 4 D of astigmatism. Fourteen of the 22 lenses were worn successfully for more than 3 months. Nineteen of 22 eyes achieved better acuity than with spectacles alone. Separation of the lens at the bonded junction and an inability to insert and remove the lens accounted for the majority of failures. We consider the SoftPerm lens whenever we encounter high astigmatism cases that have better potential acuity readings than best corrected spectacle acuity. PMID- 1499124 TI - The use of the SoftPerm lens for the correction of irregular astigmatism. AB - We evaluated the performance of the SoftPerm combined rigid gas permeable (RGP) and hydrogel lens for the visual correction of 49 eyes (30 patients) with irregular astigmatism. Follow-up was up to 15 months. An attempt was also made to compare the SoftPerm lens to its predecessor, the Saturn II lens. The most common etiology for irregular astigmatism was keratoconus. Others etiologies were penetrating keratoplasty and refractive surgery. Visual acuity improved significantly. Only two eyes were best corrected to 20/20 before fitting whereas, 13 eyes saw 20/20 after fitting. The rate of lens replacement was 0.22 lenses per eye per month. A variety of complications occurred, including corneal staining, abrasions, and edema. Complications also reflected the relative difficulty of handling of the lens, yet no vision threatening complications occurred. Overall, the SoftPerm lens is a vast improvement over the Saturn II and is a reasonable means of correction of irregular astigmatism. PMID- 1499125 TI - Contact lens manipulation of corneal topography after penetrating keratoplasty: a preliminary study. AB - We conducted a preliminary retrospective study of five eyes that had undergone penetrating keratoplasty (PK) to determine if rigid gas permeable (RGP) contact lenses could be used as splints or molds to improve postoperative corneal topography. RGP lenses were fit 3-6 months (mean: 4.1 months) after PK and 3-4 months (mean: 1.8 months) after removal of the 10-0 nylon suture. Lenses were fit to attain a contact lens resting position centered on the corneal graft. After 4 to 8 months (mean: 6.2 months) of contact lens wear, analysis of corneal topography showed a decrease in simulated keratometry cylinder from 4.7 +/- 0.6 D (mean +/- 1 standard deviation) to 1.8 +/- 0.8 D (P = 0.02) and an improvement in anterior corneal surface regularity (surface regularity index: initial = 1.40 +/- 0.2; final = 1.0 +/- 0.2; P = 0.04). Three eyes were fit with a well-centered RGP lens; two eyes were fit with lenses that rode off-center. Increased irregular astigmatism in the two eyes with decentered contact lenses suggests the importance of centering RGP lenses with respect to corneal grafts. The best corrected spectacle visual acuity either improved or remained unchanged in four of five eyes after contact lens wear. One eye demonstrated a decrease in best corrected spectacle acuity by one Snellen line after 3 months of lens wear. Further clinical studies are needed to determine the potential of postoperative use of RGP lenses to improve corneal surface regularity, to decrease astigmatism, and to optimize visual results. PMID- 1499126 TI - A prospective multicenter clinical trial to assess safety and efficacy of Menicon SF-P RGP lenses for extended wear. AB - A prospective, multicenter, national clinical trial was undertaken to assess the safety and efficacy of Menicon SF-P (melafocon A) rigid gas permeable (RGP) contact lenses for extended wear in healthy human eyes. Ten investigators enrolled 167 patients (334 eyes), of which 143 (286 eyes) were initially fit with lenses for the 12-month study. Most subjects were reexamined at 18 months or more, with findings essentially unchanged from those noted at 1 year. Two hundred two eyes (71%) completed the study. Seventy-two eyes (25%) discontinued, and 12 (4%) elected to continue extended wear. During the study, no significant adverse clinical reaction attributable to the lens was observed. Surface irritation, occasional punctate staining, and lens binding were very rare. The average wearing time was 6.2 days, mandated partially by FDA restrictions as well as patient response. As expected, keratometric shifts were principally vertical: less than 0.99 D (69%), 1.00-1.99 D (28%), and 2.00-2.99 D (4%). The majority of changes observed were toward sphericity. Two hundred lens replacements were required, 24% for adjustments in power/base curve. Only 16 lenses were replaced for warpage, and none for discoloration or crazing. Of those completing the study, 76% rated overall lens comfort and satisfaction to be very good. These results suggest that RGP lens extended wear can be safe and effective and offer patients an acceptable alternative to extended wear of disposable hydrogel lenses. PMID- 1499127 TI - Architecture of the lid-cornea juncture. AB - The details of the lid-cornea-tear film juncture influence the encounter of the lid with the top edge of an interpalpebrally fit rigid gas permeable contact lenses. During blink, fluid circulation at right angles to the globe can be hypothesized in the tear prism of the upper lid. This circulation prevents formation of a stratified tear layer, although lipid may always be present at the air interface. Water soluble or dispersed materials will be uniformly distributed in the tear film of the open eye. The collection of tears in the upper margin during a blink is shown to favor movement of tears away from the center of the upper lid. Tears on the temporal side of the center move along the upper lid to the fornix and then along the lower lid to the lower punctum. Tear fluid on the nasal side of center moves directly to the upper punctum. PMID- 1499128 TI - Contact lens articles in the literature. AB - We searched the ophthalmic literature of the past 5 years looking for patterns in the publication of contact lens articles. Contact lens articles constituted 2.59% of all ophthalmology articles. We found that a substantial percentage of the articles published in The CLAO Journal and selected optometric journals concerned contact lenses; this, however, was not the case with the major ophthalmology journals (American Journal of Ophthalmology [AJO], Ophthalmology, and Archives of Ophthalmology [Archives]). One recent contact lens development, disposable lenses, was covered by both The CLAO Journal and the major ophthalmology journals, but the coverage differed in that the orientation of the articles in the major ophthalmology journals was essentially negative. Articles about another recent development (rigid gas permeable contact lenses for extended wear), although found in The CLAO Journal, could not be found in the other ophthalmology journals. Finally, when the abstracts of all contact lens articles were reviewed, we found a negative slant to articles published in AJO and Archives. We believe that the major ophthalmology journals present a rather negative view of contact lenses; this, we think, impedes unbiased dissemination of information about new contact lens developments. PMID- 1499130 TI - Combined cataract extraction and filtering surgery. PMID- 1499129 TI - Early diagnosis of infectious keratitis with in vivo real time confocal microscopy. AB - The tandem scanning confocal microscope (TSM) was adapted for in vivo examination of the cornea in rabbits with experimental bacterial and fungal keratitis. Compared to slit lamp biomicroscopy, the TSM provides superior lateral and axial resolution and serial optical sectioning capability, which may be useful for identification of corneal pathogens in the early stages of infection. We used the TSM to examine normal rabbit eyes infected with bacteria (Bacillus cereus) and a filamentous fungus (Aspergillus). We also examined a human cornea removed by penetrating keratoplasty after a clinical diagnosis of amoebic keratitis. In the early stages of bacterial infection, slit lamp examination revealed a nonspecific minimal stromal haze and limbal injection indistinguishable from sterile ulcers and epithelial defects. With the TSM, bacteria were visible as highly refractile bodies in the epithelium and superficial stroma. Branching fungal hyphae were also easily identified by the TSM, as were Acanthamoeba cysts and parasites in the subepithelial stroma. Our results indicate that this technique may provide a new modality for quickly and accurately identifying the agent of corneal infection, thereby facilitating prompt and appropriate treatment. PMID- 1499131 TI - Combined cataract extraction and glaucoma surgery: indications. PMID- 1499132 TI - Results: combined cataract extraction and trabeculectomy. PMID- 1499133 TI - Phacotrabeculectomy with a foldable intraocular lens. PMID- 1499134 TI - Cataract extraction alone. PMID- 1499135 TI - N-glycosylation of serum proteins in disease and its investigation using lectins. AB - The majority of serum proteins are glycosylated. When disease is present, subtle changes occur in this glycosylation. These changes could provide the basis for more sensitive and more discriminative clinical tests. In order to address this possibility, a review is given of serum protein glycosylation in liver disease, inflammation and cancer. It is concluded that liver disease is accompanied by reduced sialylation and increased glycan branching; whereas cancer is accompanied by increased sialylation and increased fucosylation. In inflammation, the type of glycosylation change observed seems to depend upon the disease studied. Glycoprotein analysis can already be used for diagnosis in a few clinical situations; however, further studies are required in most diseases to provide a more detailed picture of the glycosylation changes that are occurring. This situation will change with the increasing availability of simpler techniques for glycoprotein analysis. One such group of techniques are lectin-based methods. The usefulness of these methods for glycoprotein analysis and the suitability for analysing clinical specimens are discussed in detail. PMID- 1499136 TI - Prenatal diagnosis of Niemann-Pick disease type C. AB - Niemann-Pick disease type C (NPC) was demonstrated in two successive pregnancies by strongly reduced activity of sphingomyelinase in amniotic fluid cells. By contrast, chorionic villi from the first pregnancy had shown normal sphingomyelinase activity. The prenatal diagnosis of NPC in the two fetuses was confirmed, after termination of the pregnancies, by (phospho)lipid analyses of the fetal livers, by the assay of sphingomyelinase in the fetal fibroblasts and by the demonstration of a defective esterification of exogenous cholesterol and of cholesterol accumulation by filipin staining. Retrospective analysis of cultured amniocytes for cholesterol esterification and filipin staining confirmed the feasibility of these methods for prenatal diagnosis. In a recent pregnancy in the same mother the three available methods were applied to amniotic fluid cells and an unaffected child was correctly predicted. Lipid analysis of liver tissue from the patient with NPC and the two fetuses showed a 3-5 times increased level of cholesterol, a 2-3 times increased level of sphingomyelin and a remarkable increase of bis (monoacylglyceryl) phosphate. PMID- 1499137 TI - High-performance liquid chromatographic microassay for L-alanine:glyoxylate aminotransferase activity in human liver. AB - We examine the suitability of a rapid and sensitive liquid chromatographic technique to determine L-alanine:glyoxylate aminotransferase (AGT) activity in human liver. Homogenised tissue was incubated for 30 min in the presence of substrates and the generated pyruvate was converted into the corresponding phenylhydrazone which was determined using reversed-phase high-performance liquid chromatography (HPLC). The procedure allowed the detection of the enzyme activity expressed by 10 micrograms of liver protein and was rapid enough resulting more sensitive and less time-consuming than the previous colorimetric one. We found that AGT activity in two hyperoxaluria type 1 patients was reduced as compared with controls. Also, cirrhotic patients had very low enzyme activities, even in the absence of detectable disorders of oxalate metabolism and this was ascribed to abnormal liver morphology. This may represent a misleading drawback if diagnosis of type 1 primary hyperoxaluria (PH1) uniquely relies on AGT assay. PMID- 1499138 TI - Serum triglyceride and insulin levels are associated with erythrocyte sodium lithium counter-transport activity in normoglycaemic individuals. AB - The relationship between erythrocyte sodium-lithium counter-transport activity, serum insulin, lipids and demographic factors was examined in 93 normoglycaemic predominantly normotensive individuals with mild fasting hypercholesterolaemia (greater than 5.2 mmol/l). The major significant univariate correlates of sodium lithium counter-transport activity were fasting serum triglycerides, HDL cholesterol, the ratio of fasting glucose: insulin, apo A1, alcohol consumption and apo B. Stepwise multiple regression analysis revealed 24% of the variability in sodium-lithium counter-transport activity could be accounted for by independent contributions of fasting serum triglycerides, alcohol consumption, the fasting glucose/insulin ratio and apo A1 and ANOVA confirmed a significant relationship with fasting insulin measures that was independent of serum triglycerides (P less than 0.05). The relationship between erythrocyte sodium lithium counter-transport activity and concentrations of serum triglycerides, HDL components, insulin and additionally alcohol consumption, could reflect the influence of those variables on erythrocyte structure and function. PMID- 1499139 TI - Liver transplantation modifies serum cholestanol, cholesterol precursor and plant sterol levels. AB - Proportions of cholesterol precursors (squalene, delta 8-cholestenol, desmosterol and lathosterol), plant sterols (campesterol and sitosterol) and cholestanol to cholesterol in serum were measured before and serially after liver transplantation in eight patients with primary biliary cirrhosis (PBC) and three with acute liver necrosis. The preoperative proportions of cholestanol were 12 and 3-times higher in the PBC and necrosis groups, respectively, than in a control group of 27 individuals, while those of lathosterol were low in both groups and the campesterol/sitosterol ratio in the PBC group. During the operation the proportions of cholestanol fell sharply and those of lathosterol rose especially in the PBC group. During the postoperative follow-up of 5 weeks the proportions of the non-cholesterol sterols were markedly improved especially in the necrosis group yet those of cholestanol remained high and the campesterol/sitosterol ratios low, particularly in the PBC group. The proportions of lathosterol increased gradually almost to the control limits within the postoperative 5-week period, whereas those of desmosterol decreased. The non cholesterol sterol values were not related to acute rejections, while significant correlations of cholestanol to liver function tests was found especially at the end of the follow-up. PMID- 1499140 TI - A simple electrophoretic method for separating elevated liver and bone alkaline phosphatase isoenzymes in plasma after neuraminidase treatment. PMID- 1499141 TI - 2,3-Butanediol: a potential interfering substance in the assay of ethylene glycol by an enzymatic method. PMID- 1499142 TI - Oligosaccharides in (galacto)sialidosis urine. PMID- 1499143 TI - Enzyme immunoassay for serum cortisol. PMID- 1499144 TI - Effect of long-term storage on human plasma osteocalcin level. PMID- 1499145 TI - Influence of workload on the antihypertensive effect of exercise. AB - 1. The relation between workload and the antihypertensive effect of exercise therapy in hypertensive patients, and the mechanism of that effect, were investigated. 2. Twenty-six patients participated in the study and were randomly assigned to 10 weeks of either low or high workload exercise. In the low workload group, 16 mild hypertensive patients were treated with bicycle ergometer exercise at approximately 50% of their maximum oxygen consumption (VO2max) for 60 min three times a week for 10 weeks. In the high workload group, 10 mild hypertensive patients exercised on the same schedule, but at approximately 75% of VO2max. 3. After 10 weeks of exercise, the low workload group had significantly lower systolic (9 mmHg), mean (6 mmHg) and diastolic (6 mmHg) blood pressures. In the high workload group, decreases in systolic (3 mmHg), mean (4 mmHg) and diastolic (5 mmHg) blood pressure were not statistically significant. 4. In the low workload group, changes in haemodynamic and humoral variables were not significant, except for a reduction in plasma norepinephrine at week 7. Cardiac index and plasma norepinephrine tended to decrease. In the high workload group, plasma norepinephrine and the renin-angiotensin system were transiently stimulated after 4 weeks of exercise. Stroke volume significantly increased (+26.4%) after 10 weeks of high workload exercise. 5. Based on these results and better patient compliance with the exercise programme in the low workload group than in the high workload group, low workload exercise therapy was recommended to mild hypertensive patients. PMID- 1499146 TI - Effects of acute superior cervical ganglionectomy on cerebral blood flow and metabolism in stroke-prone spontaneously hypertensive rats subjected to cerebral ischaemia. AB - 1. The effects of acute bilateral superior cervical ganglionectomy on cerebral blood flow and metabolism were investigated in stroke-prone spontaneously hypertensive rats (SHRsp), before and during cerebral ischaemia. 2. The resting cerebral blood flow was comparable between the control and denervated animals. 3. There was no significant difference in cerebral blood flow or concentration of tissue energy metabolites (adenosine triphosphate [ATP], lactate and pyruvate) between the sham-operated control and denervated animals during ischaemia. 4. The results suggest that sympathetic innervation of cerebral vessels originating from superior cervical ganglia may not play a major role in the progression of cerebral ischaemia in SHRsp. PMID- 1499147 TI - The effect of ovine prolactin on the epididymal sialic acid concentration in male rats. AB - 1. Previous experiments have shown that the level of sialic acid in the epididymis is influenced by factors originating in the testis. 2. To exclude interference from these factors, both orchidectomized and duct-ligated rats were used to study the potential role of prolactin in the epididymis. 3. When ovine prolactin was injected in orchidectomized rats, a dose-related increase in the level of sialic acid was observed in the epididymis. 4. That this action of prolactin is independent of androgen was confirmed by studies using bromocriptine, which decreases circulating endogenous prolactin. 5. The physiological role(s) of epididymal sialic acid production in response to prolactin remain to be established. PMID- 1499148 TI - Platelet-activating factor in bronchoalveolar lavage fluid of patients with adult respiratory distress syndrome. AB - 1. To clarify the role of platelet-activating factor (PAF) in the development of adult respiratory distress syndrome (ARDS), we performed bronchoalveolar lavage (BAL) in 19 patients with ARDS and examined cell populations, albumin concentrations and PAF levels. PAF levels were measured by a newly developed radioimmunoassay. 2. In the BAL fluid of ARDS patients, neutrophil percentages and albumin concentrations markedly increased compared with control subjects. 3. PAF was detected in 14 of 19 patients with ARDS, whereas it did not exist in the control subjects. 4. Furthermore, we investigated the priming effect of recombinant human tumour necrosis factor-alpha (TNF alpha), which is known to be one of the most important mediators in the development of ARDS, on PAF production induced by the calcium ionophore in neutrophils. 5. Pre-incubation with TNF alpha dose-dependently increased both extracellular and intracellular PAF production in neutrophils. 6. These results suggest that PAF might play an important role in the development of ARDS. PMID- 1499150 TI - Ageing has no effect on the volume density of hepatocytes, reticulo-endothelial cells or the extracellular space in livers of female Sprague-Dawley rats. AB - 1. The hepatic reticulo-endothelial cell population is generally assumed to increase in size, along with the liver, during ageing in rats. However, this has not been rigorously established. 2. Using electron microscopy and stereological techniques, the present study has shown that the volume densities of hepatocytes and Kupffer cells (and probably also of endothelial cells, fat storing cells and the extracellular space) of the livers of female Sprague-Dawley rats are the same at 2 and 24-25 months of age. 3. This result indicates that the increase in size of the liver during ageing in the rat is associated with an equivalent increase in the volume of each cell population and the extracellular space. PMID- 1499149 TI - Comparative effects of dopamine and dobutamine on the pulmonary haemodynamic response to hypoxia in dogs ventilated with a hypoxic gas mixture. AB - 1. The effects of dopamine and dobutamine on the pulmonary haemodynamic response to hypoxia were studied in nine anaesthetized dogs under hypoxaemia induced by ventilation with hypoxic gas mixture. 2. From the present study, only dopamine infusion reduced arterial oxygenation during hypoxic hypoxaemia, whereas catecholamine maintained it at the same level during normoxaemia. 3. A redistribution of perfusion to the pulmonary vasculature may be related to a reduction of arterial oxygenation with dopamine infusion during hypoxic hypoxaemia. 4. It is presumed that an increase in pulmonary blood flow would emphasize an inhibition of hypoxic pressor response in the pulmonary vasculature, which may not be a direct effect of dopamine. PMID- 1499151 TI - DNA elimination and its relation to quantities in the macronucleus of Tetrahymena. AB - The macronucleus of Tetrahymena contains a large number of DNA molecules of subchromosomal size. They belong to about 270 species each one occurring at an average number of 45 copies. Macronuclei divide unequally and nothing is known of segregation control. This and the elimination and degradation of DNA during macronuclear amitosis make the clonal stability of macronuclei a problem of qualitative and quantitative control on a subchromosomal level. We studied the contribution of DNA elimination to the quantitative composition of the macronucleus cytophotometrically in single cells of different strains. This was done under standard conditions and under conditions known to influence the amount of macronuclear DNA. The following results were found: Elimination of DNA occurs at almost every division. The size of the elimination body is highly variable but still positively correlated with the macronuclear DNA content. In T. thermophila the amount of eliminated DNA is 2.5% of the G2 content and is not dependent on the growth state. It varies with species, amounting to as much as 8% in T. pigmentosa. During conditions which increase the macronuclear DNA content, very little DNA is eliminated. On the other hand, large amounts are eliminated under other conditions causing the macronuclear DNA content to decrease. DNA to be eliminated at division is synthesized at the same time as bulk DNA. We developed a computer program which helps us study the effects of DNA elimination and unequal divisions upon the copy numbers of subchromosomal DNA classes.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1499152 TI - Variable copy number of macronuclear DNA molecules in Tetrahymena. AB - In Tetrahymena, the DNA of the macronucleus exists as very large (100 to 4,000 kb) linear molecules that are randomly partitioned to the daughter cells during cell division. This genetic system leads directly to an assortment of alleles such that all loci become homozygous during vegetative growth. Apparently, there is a copy number control mechanism operative that adjusts the number of each macronuclear DNA molecule so that macronuclear DNA molecules (with their loci) are not lost and aneuploid death is a rare event. In comparing Southern analyses of the DNA from various species of Tetrahymena using histone H4 genes as a probe, we find different band intensities in many species. These differences in band intensities primarily reflect differences in the copy number of macronuclear DNA molecules. The variation in copy number of macronuclear DNA molecules in some species is greater than an order of magnitude. These observations are consistent with a developmental control mechanism that operates by increasing the macronuclear copy number of specific DNA molecules (and the genes located on these molecules) to provide the relatively high gene copy number required for highly expressed proteins. PMID- 1499153 TI - Stable and unstable transformation by microinjection of macronucleoplasm in Paramecium. AB - Transformation by microinjection of macronucleoplasm in Paramecium caudatum was investigated. Macronucleoplasm with three genetic markers (behavior, trichocyst, and mating type) was injected into the macronucleus. To facilitate microinjection, in most cases, paramecia were immobilized in a gelatin (7.5%) solution. The injected cells began to express a dominant gene (cnrA+ or cnrB+) of the donor 9-24 hr after injection. Expression did not require cell division suggesting injected macronucleoplasm was capable of expressing a phenotype. The amount of injected macronucleoplasm appears to correlate with the frequency of successful expression but not to correlate with the time required for expression. After a number of fissions, the injected cells produced clones which had cells expressing the phenotype of the donor. This suggests that injected macronucleoplasm was replicated and expressed in the recipient cell lines. The transformed clones were classified into two groups. In one group, transformation was stable. All cell lines derived from the injected cells expressed a phenotype similar to the heterozygote of donor and recipient cells. In the other group, transformation was unstable. During the first five to seven fissions after injection, at each division, cells produced one daughter cell which later reverted to the recipient phenotype. After this unstable period, cells no longer produced the recipient phenotype but produced the donor phenotype exclusively. Donor and recipient phenotypes were, thus, segregated in different cell lines. Observation of genetic markers and analysis by computer simulation shed light on the mode of transmission of injected macronucleoplasm. In stable transformation, injected macronucleoplasm appears to be distributed equally to daughter cells.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1499154 TI - Rate of phenotypic assortment in Tetrahymena thermophila. AB - During vegetative, asexual reproduction in heterozygous Tetrahymena thermophila, the macronucleus divides amitotically to produce clonal lineages that express either one or the other allele but not both. Because such phenotypic assortment has been described for every locus studied, its mechanism has important implications concerning the development and structure of the macronucleus. The primary tools to study assortment are Rf, the rate at which subclones come to express a single allele stably, and the output ratio, the ratio of assortee classes. Because Rf is related to the number of assorting units, a constant Rf for all loci suggests that all genes are maintained at the same copy number. Output ratios reflect the input ratio of assorting units, with a 1:1 output ratio implying equal numbers of alleles at the end of macronuclear development. Because different outcomes would suggest a different macronuclear structure, it is crucial that these parameters be accurately measured. Although published Rf values are similar for all loci measured, there has been no commonly accepted form of presentation and analysis. Here we examine the experimental determination of Rf. First, we use computer simulation to describe how the variability inherent in the assortment process affects experimental determination of Rf. Second, we describe a simple method of plotting assortment data that permits the uniform calculation of Rf, and we describe how to measure Rf accurately in instances when it is possible to score only the recessive allele. Using this method to produce truly comparable Rfs for all published data, we find that most, if not all, loci assort at Rfs consistent with approximately 45 assorting units, as has been asserted. PMID- 1499155 TI - Inheritance of the group I rDNA intron in Tetrahymena pigmentosa. AB - We have previously argued from phylogenetic sequence data that the group I intron in the rRNA genes of Tetrahymena was acquired by different Tetrahymena species at different times during evolution. We have now approached the question of intron mobility experimentally by crossing intron+ and intron- strains looking for a strong polarity in the inheritance of the intron (intron homing). Based on the genetic analysis we find that the intron in T. pigmentosa is inherited as a neutral character and that intron+ and intron- alleles segregate in a Mendelian fashion with no sign of intron homing. In an analysis of vegetatively growing cells containing intron+ and intron- rDNA, initially in the same macronucleus, we similarly find no evidence of intron homing. During the course of this work, we observed to our surprise that progeny clones from some crosses contained three types of rDNA. One possible explanation is that T. pigmentosa has two rdn loci in contrast to the single locus found in T. thermophila. Some of the progeny clones from the genetic analysis were expanded for several hundred generations, and allelic assortment of the rDNA was demonstrated by subcloning analysis. PMID- 1499156 TI - Immunocytochemical analysis of secretion mutants of Tetrahymena using a mucocyst specific monoclonal antibody. AB - Dense-core granules represent an adaptation of specialized secretory cells to facilitate stimulus-regulated release of stored proteins. Such granules are a prominent feature of mammalian neuroendocrine and exocrine cells and are also well developed in the ciliates. In Tetrahymena thermophila, the ability to generate mutants in dense-core granule biosynthesis and fusion presents a versatile system for dissecting steps in regulated exocytosis. We have previously shown that defective granules in such mutants could be characterized by several biochemical criteria, including buoyant density, which increases during maturation, and the degree of proteolytic processing of the content precursors. We have now used indirect immunofluorescence, taking advantage of a monoclonal antibody directed against a granule protein, to visualize the morphology and distribution of both granules and putative granule intermediates in mutant and wild-type cells. The results are consistent with the biochemical analysis and extend our characterization of the mutants, allowing us to distinguish four classes. In addition, the assay represents a powerful technique for diagnosis of new mutants. PMID- 1499157 TI - Genetic characterization of Tetrahymena thermophila mutants unable to secrete capsules. AB - Under appropriate conditions, Alcian Blue-induced exocytosis of Tetrahymena mucocysts leads to formation of a capsule that surrounds the cell. This phenomenon is an example of regulated secretion, a mechanism of fundamental significance in eukaryotic cells. In order to dissect genetically the mechanism of mucocyst biogenesis and regulated exocytosis, mutants unable to form capsules (Caps-) were isolated. In this paper we report a genetic characterization of Caps mutants in this collection. The mutations in mutants SB255 and SB281 behave as single recessive Mendelian mutations. The mutation in SB251 is restricted to the macronucleus, and could not be further characterized by the genetic methods we used. Complementation tests suggest the existence of at least 2 genes, named exoA and exoB; additional mutant loci are likely to be included in the mutant collection. Deletion mapping using nullisomic strains showed that exoA and exoB are located on the left arm of chromosome 4. The exo-3 mutation, which behaves as recessive and complements with exoA1 in SB255 and exoB2 in SB281, maps to chromosome 3. These Caps- mutants may be useful for the elucidation of the developmental pathway of mucocyst biogenesis and the control of regulated secretion in eukaryotic cells. PMID- 1499158 TI - Genetic characterization of the secretory mutant MS-1 of Tetrahymena thermophila: vacuolarization and block in secretion of lysosomal hydrolases are caused by a single gene mutation. AB - The genetics and phenotypic features (light and electron microscopy) of a secretory mutant, MS-1 of Tetrahymena thermophila blocked in secretion of lysosomal acid hydrolases have been analyzed. Although blocked constitutively in secretion, MS-1 contains active lysosomal hydrolases in amounts equivalent to the wild type. The 3:1 segregation in F-2 in sib crosses and the 1:1 segregation in test crosses indicate that the block in secretion of lysosomal hydrolases is controlled by a recessive single gene locus termed sec. The sec allele of MS-1 proved also to be responsible for the highly vacuolarized phenotype the mutant developed when it was transferred from nutrient medium into buffers of low ionic strength. Deletion mapping by crossing MS-1 with nullisomic strains, all secreting lysosomal hydrolases at wild-type rates, was performed. The sec phenotype was expressed in monosomic-4 progeny only, indicating that the sec allele is located on chromosome 4 of T. thermophila. PMID- 1499159 TI - Locus-dependent profiles of the rescue of nonexcitable behavioral mutants during conjugation in Tetrahymena thermophila. AB - The Tetrahymena nonreversal (TNR) mutants of Tetrahymena thermophila are behavioral mutants with nonexcitable membranes. When cells of the tnrB mutant were mated with wild type, a phenotypic change occurred about 1 h after pair formation. The pairs began to lose their heterotypic character in stimulation solution containing high potassium and, within 1 1/2 h, they were not distinguishable from the wild-type homotypic pairs. On the contrary, although pairs of the tnrA and wild type also lost their heterotypic character about 1 1/2 h after pair formation, they never showed a full response as wild-type homotypic pairs. When tnrA was mated with tnrB, more than 50% of pairs expressed a heterotypic pair character 2 h after pair formation, consistent with the tnrB defect having been rescued but not the tnrA defect. Thus, conjugation rescue of the mutant phenotype is locus dependent and probably reflects the nature of the gene products controlling voltage-dependent Ca2+ channels. PMID- 1499160 TI - Ciliate developmental genetics. PMID- 1499161 TI - Genes and structural patterns in ciliates: Vance Tartar and the "cellular architects". AB - The one form of cytoplasmic inheritance that has not been assimilated into the Central Dogma is the inheritance of surface structural patterns, a phenomenon most clearly expressed in ciliates. Vance Tartar, although he worked with a genetically undomesticated organism (Stentor coeruleus), provided early evidence for the crucial role of clonally propagated features of the cell cortex. He showed that the capacity for development of cortical organelle systems is associated with a particular relational feature, the "locus of stripe contrast" (LSC), and that clonally inherited cortical variants (homopolar doublets) could be created at will by microsurgical operations that duplicated the LSC. Tartar also hoped to demonstrate the existence of what David Nanney called "cellular architects" by provoking stentors to carry out entirely novel types of morphogenetic performances. He eventually acknowledged failure, although the bizarre juxtapositions by which he attempted to elicit such novel performances did bring about specific and illuminating defects in cortical development. Subsequent analyses of similar defects in other ciliates revealed not the unitary "pattern factor" postulated by Tartar, but rather a hierarchy of distinct patterning mechanisms. Nonetheless, by pursuing an embryological approach toward morphogenesis in a highly regulative ciliate, Tartar uncovered relational aspects of pattern-determination; this, in my view, delineates the major problem that we must solve to gain understanding of intracellular patterning. PMID- 1499162 TI - The influence of fission line expression on the number and positioning of oral primordia in the cdaA1 mutant of Tetrahymena thermophila. AB - During cytokinesis, furrowing creates new boundaries for daughter cells. Following a shift to a restrictive temperature, cells of the temperature sensitive cell-division-arrest (cdaA1) mutant of Tetrahymena thermophila complete development of the oral apparatus for the prospective posterior daughter cell before becoming arrested in cytokinesis. When maintained under weak restrictive conditions (35 degrees C), some of the chains were arrested prior to the start of fission line formation (D-shaped chains), whereas others manifested rudimentary unilateral furrowing on the ventral side (B-shaped chains). In their second cell cycle following the temperature shift, the D-shaped chains usually formed only one oral primordium, at a position highly correlated with the length of the entire chain. The B-shaped chains always produced two separate oral primordia, located at irregular positions anterior and posterior to the division furrow, often close to the posterior oral apparatus produced during the first cycle. These results suggest that the formation of the fission line sets a reference boundary to assess the number of oral primordia and influence their position, that appear during subsequent morphogenetic episodes. They also indicate that, during cell division cycles, pre-existing oral apparatuses do not strongly inhibit the formation of new oral apparatuses in their close vicinity. PMID- 1499163 TI - Studies on morphological outcome of cyclosporine-associated arteriolopathy after discontinuation of cyclosporine in renal allografts. AB - Cyclosporine (CSA)-associated arteriolopathy (CAA) is the second most frequent morphological diagnosis in renal allografts and its final outcome remains unclear. The present study was performed to clarify the morphological outcome of CAA by follow-up histological analysis after stopping CSA. Furthermore, the clinical management of patients showing CAA is discussed. Most of the patients came from our early experience with CSA between 1981-1983 when CSA doses and trough levels were high. Twenty recipients were divided into two groups according to the presence of CAA after stopping CSA: group A (n = 9) showed persistent CAA and group B (n = 11) showed no CAA. The majority of the patients, including five incomplete remission in group A, showed obvious improvement of CAA even if the arterioles were severely affected. Improvement of CAA was noted a few months after stopping CSA or after lower dose CSA therapy. There were no significant differences in CSA blood levels or duration of CSA therapy between the groups. The severity of preexistent CAA was significantly greater in group A. Only two patients who died from malignant tumor showed exacerbation of CAA. Eight patients died and eight grafts were lost, seven due to vascular rejection and one to hemolytic uremic syndrome-like CAA. Poor renal function was also noted in four cases with functioning graft owing to vascular rejection even though the improvement of CAA was evident. The complete regression of CAA and the remodelling of arterioles showing well preserved vascular patency were frequently found after stopping or reducing the dose of CSA.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1499164 TI - Idiopathic membranous glomerulonephritis: a clinicopathologic and quantitative morphometric study. AB - We evaluated clinical and morphological findings in 254 patients (138 men and 116 women), with idiopathic membranous glomerulonephritis (IMGN). The mean age was 44 years. At time of biopsy proteinuria was found in 98%, nephrotic syndrome (NS) in 45.2%, hypertension in 10%, elevated serum creatinine concentration of greater than or equal to 1.4 g/dl in 24%, and markedly decreased Ccr (less than or equal to 40 ml/min) in 12.5% of the patients. Of 254 patients, 51 (20%) were classified as Stage I, 131 (52%) as Stage II, 52 (20.5%) as Stage III, 9 (3.5%) as Stage IV and 11 (4.3%) as Stage V, which was a relapsing form. Both intraglomerular, peripheral electron dense deposit-size and mean thickness of the glomerular basement membrane (GBMt) were analyzed by ultrastructural morphometric methods. In patients with NS, both the mean deposit-size and the mean GBMt were largest when compared to all others (p less than 0.01). The largest subepithelial deposits (SED), in mean, were observed in Stages II and V, while the largest incorporated deposits (ICD) were measured in Stages II and IV. The mean GBMt was largest in Stage III. Furthermore, there were strong correlations between the degree of proteinuria and the deposit-size (r = 0.603, p less than 0.001), and GBMt (r = 0.456, p less than 0.001). The GBMt showed a correlation with serum creatinine concentration (r = 0.476, p less than 0.001) and Ccr (r = 0.471, p less than 0.001). We concluded that the size of the electron dense deposits and GBM thickness play an important role in the clinical manifestation of IMGN. PMID- 1499166 TI - In vitro production of interleukin-1 from blood mononuclear cells of patients on chronic hemodialysis therapy. AB - A monocyte defect is thought to be involved in the impaired immune response in patients on regular hemodialysis therapy. As an indicator of cell function, we studied in vitro IL-1 beta production of mononuclear cells from hemodialysis patients in comparison to normal controls. Mononuclear cells were stimulated with endotoxin or Staphylococcus epidermidis in parallel with control incubations in tissue culture medium alone. Spontaneous as well as stimulated total IL-1 beta production (cell-associated plus extracellular) did not differ significantly in cells obtained from patients compared to those from normal controls. However, the relative amounts of IL-1 beta released into the cell supernatants were significantly reduced in mononuclear cells from hemodialysis patients when stimulated with endotoxin but not with Staphylococcus epidermidis. These data indicate a stimulus-dependent defect in the mechanism of IL-1 beta release. As IL 1 is necessary for T-cell activation this alteration in mononuclear cell function may play a role in the impaired cellular immunity observed in patients on chronic hemodialysis therapy. PMID- 1499165 TI - Protein catabolism in sham-hemodialysis: the effect of different membranes. AB - To study whether the contact between dialysis membrane of various materials and blood may trigger protein catabolism in muscle and thus contribute to protein depletion in hemodialysis patients we measured the exchange of free amino acids across the leg in healthy subjects undergoing sham-hemodialysis (i.e. in vivo passage of blood through a dialyzer without circulating dialysate). The effect of dialyzers with regenerated cellulose (group CU, n = 16), cellulose acetate (group CA, N = 8) and polysulfone membranes (group PS, n = 8), respectively was studied. Plasma amino acid concentrations were measured in arterial and femoral venous blood and leg blood flow was determined by venous occlusion plethysmography. In group CU the total efflux of all measured amino acids from leg tissues (muscle) increased from 167 +/- 21 nmol/min/100 g tissue in the basal state to 308 +/- 41 nmol/min/100 g tissue at 345 minutes after the start of sham-hemodialysis procedure (p less than 0.01) indicating a protein catabolic effect of contact between blood and regenerated cellulose membranes. In contrast sham-hemodialysis in group CA and group PS, respectively, did not result in significant increases in amino acid efflux from the leg implying that the protein catabolic effect of blood membrane contact depends on the chemical properties of dialysis membranes. In group CU sham-hemodialysis resulted in enhanced net protein breakdown. Increases in arterial concentrations and leg release of 3-methylhistidine suggest that this may be due primarily to increased protein breakdown. PMID- 1499167 TI - Hepatitis virus infection (HBV and HCV) in eleven Japanese hemodialysis units. AB - To evaluate hepatitis C virus (HCV) and hepatitis B virus (HBV) infection in hemodialysis (HD) units, serum samples from 607 HD patients and 150 staff members at 11 HD units in Japan were collected, and were compared with those from 704 ordinary blood donors as a control. Serum samples subjected to a first generation ELISA for antibody to HCV (anti-C100-3) and were tested by ELISA for HB surface antigen (HBs-Ag), antibody to HBs-Ag, and antibody to HB core antigen (anti-HBc) as HBV markers. We also tested for HCV infection with a second generation ELISA (for antibodies to C22-3, C33c, and C100-3) in 120 HD patients and 30 staff members at 2 selected HD units. Of 607 HD patients, 104 (17%) were positive for anti-C100-3 and 221 (36%) for HBV markers, indicating a much higher prevalence of HCV and HBV infection among HD patients than among ordinary blood donors (0.9% and 18%, respectively). Of 159 patients without a history of blood transfusion, 17 (11%) were positive for anti-C100-3, showing that HCV infection can be acquired without transfusion. The incidence of anti-C100-3 varied from 0% to 53% at different HD units, and HBV markers varied from 17% to 50%. Our study detected a high prevalence of co-infection with HBV and HCV, suggesting that HCV infection may contribute to chronic liver dysfunction in HD patients. Out of 150 staff members, 3 (2%) were positive for anti-C100-3, whereas 25 (17%) were positive for anti-HBc (indicating prior HBV infection).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1499168 TI - Antibody to hepatitis C virus increases with time on hemodialysis. AB - We studied whether chronic hemodialysis is associated with an increased risk of exposure to hepatitis C virus. Utilizing a first generation Elisa assay (C-100 Elisa, Ortho Diagnostic Systems, Raritan, NJ) and the Chiron RIBA HCV second generation assay (RIBA, Chiron, Emeryville, CA and Ortho Diagnostic Systems, Raritan, NJ), antibody to HCV was found in 31 of 87 hemodialysis patients (36%). Patients on hemodialysis less than 2 years had an antibody incidence of 15% (n = 46), as contrasted with a 59% incidence for patients on dialysis greater than or equal to 2 years (n = 41). We were unable to demonstrate a correlation of HCV antibody positivity with history of blood transfusion. The overall incidence is higher than previously reported for hemodialysis patients in the United States. The very high incidence found in patients on dialysis greater than or equal to 2 years suggests that factors in the hemodialysis unit might contribute to the spread of virus. PMID- 1499169 TI - Prevalence and incidence of hepatitis C virus (HCV) in hemodialysis patients: study of risk factors. AB - The prevalence of antibodies against hepatitis C virus (HCV) was assessed in 246 hemodialysis patients who attended a dialysis unit in Bari, using a recombinant enzyme immunoassay test (Abbot Lab.). Fifty-six (22.8%) sera were reactive to anti-HCV. The reactivity was confirmed in 46 specimens (18.7%) using the Abbott EIA HCV neutralization test. The anti-HCV prevalence was higher in males than in females and increased with age, duration of dialysis and number of transfusions. Moreover, a correlation between the presence of anti-HCV and the persistent increase of ALT was noted. The HCV-infection attack rate was calculated using the frozen sera collected from 1984 to 1990: the incidence of infection in the first year was 6.1%, and in following years 4.6%, 4.9%, 3.1%, 2.1% and 2.2%, respectively. PMID- 1499170 TI - Clostridium difficile infection--a poor prognostic sign in uremic patients? AB - Uremia has been reported as a risk factor for the occurrence of infection with Clostridium difficile. During the two-year period 1984-86, 110 episodes of Clostridium difficile infection were encountered in 70 patients on a nephrology ward. Sixty-two patients had chronic renal failure and eight had acute renal failure. Sixty-seven of the patients were uremic and were treated with hemodialysis (n = 35), CAPD (n = 21), intermittent peritoneal dialysis (n = 6) or conservatively with a low protein diet (n = 5). Most of the patients were female (n = 41) and elderly (64 +/- 2 years). Malnutrition was common as indicated by low serum albumin concentrations (26 +/- 1 g/l) prior to the Clostridium difficile infection. Clostridium difficile infection was confirmed by stool culture and/or cytotoxin assay. Asymptomatic infections were found in eight patients. The highest relative risks of subsequent Clostridium difficile infection were calculated for patients treated with cephalosporins and isoxazolyl penicillins. All patients were treated with vancomycin, which often resulted in a dramatic improvement. One to six relapses of Clostridium difficile infection were observed in 22 of the patients. Sixty of the original 70 patients died during the five-year follow-up period. Thirty-four patients died during the first year of follow-up. Seven patients were transplanted, two are still on CAPD treatment and one has only moderate chronic renal failure (serum creatinine 200 mumol/l). Elderly debilitated uremic patients are especially susceptible to infection with Clostridium difficile which may be a poor prognostic sign in chronic renal failure.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1499171 TI - Jugular-axillary vein bypass for salvage of arterio-venous fistula in subclavian vein stenosis: report of two cases. PMID- 1499172 TI - Urinary excretion of glycated albumin in insulin-dependent diabetic patients with micro- and macroalbuminuria. AB - Non-enzymatic glycosylation (glycation) involves both circulating proteins, such as albumin and structural proteins, such as the components of the glomerular basement membrane. Glycated albumin is more anionic than unmodified plasma albumin at physiologic pH. Preferential urinary excretion of glycated proteins has occasionally been reported in diabetes. We therefore investigated the selectivity index (renal clearance of non-glycated/glycated albumin) in 25 insulin-dependent diabetic patients (17 with microalbuminuria and 8 with macroalbuminuria), and 19 healthy subjects. The selectivity index was significantly higher (p less than 0.01) in the microalbuminuric patients than in the macroalbuminuric patients and the control subjects: 1.11 +/- 0.03 SEM vs 0.94 +/- 0.08 vs 0.98 +/- 0.02. These results are not consistent with preferential urinary excretion of glycated albumin in insulin-dependent diabetic patients with increased urinary albumin excretion. PMID- 1499173 TI - Serial chest thumps for the treatment of ventricular tachycardia in patients with coronary artery disease. PMID- 1499174 TI - Diagnostic value of technetium-99m-MIBI as a myocardial perfusion imaging agent: comparison of long and short intervals between rest and stress injections. AB - To assess the diagnostic value of technetium-99m-MIBI (99mTc-MIBI) as a myocardial perfusion imaging agent, and if rest and exercise scans could be performed on the same day, 21 patients with coronary artery disease were studied. Qualitative planar 201-thallium (201Tl) scans, coronary angiography, or both were also performed (median between studies 11 days). In 10 patients an injection of 740 mBq of 99mTc-MIBI at stress was followed by a second injection of 740 mBq at rest 24 h later (long interal) (LI). In 11 patients injection of 370 mBq at rest was followed 3 h later by an injection of 740 mBq at stress (short interval) (SI). Exercise scans were performed to similar maximal work load (LI = 6.6 +/- 1.8 METs; SI = 6.3 +/- 1.7 METs; 201Tl = 6.8 +/- 1.2 METs; p = NS) and double product (LI = 19551 +/- 7370; SI = 19900 +/- 6797; 201Tl = 19965 +/- 5282; p = NS). Overall, 99mTc-MIBI and 201Tl agreed in 92% of the patients tested and in 165 of 180 (92%) left ventricular segments in both 99mTc-MIBI protocols using short and long intervals between injections. In 15 patients with significant stenosis, 99mTc-MIBI correctly identified 13 patients (sensitivity of 87%). Thus, 99mTc-MIBI is a useful imaging agent with similar diagnostic value as 201Tl. In spite of its lack of myocardial redistribution, 99mTc-MIBI rest and exercise scans performed on the same day seem to have a similar concordance rate with 201Tl as when performed on separate days. PMID- 1499175 TI - Pulsed Doppler echocardiographic indices of left ventricular diastolic function in normal subjects. AB - To establish the normal limits for various pulsed Doppler echocardiographic indices of left ventricular diastolic function, 92 healthy volunteers aged from 5 to 75 years were prospectively studied. The influence of various variables including age, gender, body surface area, fractional shortening, and left ventricular mass on these parameters was also assessed. Mean (2SD) values for 15 direct and 11 derived parameters were analyzed from transmitral inflow velocity waveform. No statistically significant differences were observed between males and females for any of these parameters. On stepwise multivariate linear regression analysis, age was found to be an independent strong determinant (p less than 0.001) of peak velocity of early diastolic filling wave, area of atrial filling period, deceleration slope, normalized peak filling rate, and early filling fraction. There was a significant correlation between heart rate and time to peak early diastolic velocity, total diastolic time period, early diastolic period, atrial filling period, and atrial filling fraction. It was further observed that a significant correlation (p less than 0.001) persisted between both age and heart rate with area of early filling period, one-third filling area, one-half filling area, ratio of early to atrial peak velocity and area, atrial filling fraction, and one-third filling fraction. None of the parameters were found to correlate with fractional shortening or left ventricular mass. Thus an effort was made to establish normal limits for various Doppler-derived parameters in healthy volunteers for future comparison in diseased states.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1499176 TI - Hemofiltration as treatment for patients with refractory heart failure. AB - Hemofiltration was performed in 15 patients with refractory congestive heart failure. All of these patients had oliguria, although intensive treatment with diuretics, digitalis, vasodilators, and catecholamines was prescribed. Hemofiltration was performed under hemodynamic monitoring in 14 patients. The water removal by hemofiltration decreased pulmonary arterial pressure, pulmonary capillary wedge pressure and right atrial pressure. Despite these hemodynamic improvements, nine patients (60%) died within one month after the start of hemofiltration; the causes were fatal arrhythmia in three, renal failure in two, sepsis in one and irreversible cardiogenic shock in three. Oliguria for over 15 h or a serum creatinine concentration of more than 4.0 mg/dl at the start of hemofiltration related to poor prognosis. In view of these results, hemofiltration for refractory heart failure should be started earlier and performed carefully in order to avoid arrhythmia, cardiogenic shock, and other complications. PMID- 1499177 TI - QT interval shortening and ST elevation in intracoronary ECG during PTCA. AB - Percutaneous transluminal coronary angioplasty (PTCA) can provide a unique model of transient and reversible myocardial ischemia. The aim of this study was to assess the serial changes in QT interval during elective PTCA-induced transient ischemia. The serial changes in QT interval before, during, and after PTCA of the left anterior descending artery (LAD) were measured in patients who showed ST elevation in intracoronary electrocardiogram. Twelve consecutive patients who showed ST-segment elevation during PTCA-induced ischemia anterior precordial leads of the electrocardiogram (ECG) were enrolled in the present study. Target lesions for PTCA were all in the LAD. There were six patients with angina pectoris, two with non-Q-wave infarction, and four with Q-wave myocardial infarction. During balloon inflation, QTc interval shortened in both intracoronary ECG (ic-ECG) (0.472 +/- 0.013 vs 0.436 +/- 0.014) and surface ECG (0.462 +/- 0.012 vs 0.438 +/- 0.011). However, a significant shortening of the QT interval was more rapidly observed in the ic-ECG (20 s) than in the surface ECG (40 s). We conclude that the QT interval in both ic-ECG and surface ECG becomes shortened in PTCA-induced myocardial ischemia, and that the ic-ECG might be a good probe for detecting survived viable myocardium in the infarcted zone. PMID- 1499178 TI - Histologic evidence of myocardial damage in apparently healthy subjects with ventricular arrhythmias and myocardial dysfunction. AB - The association of ventricular arrhythmias and myocardial dysfunction could be considered an early step toward cardiomyopathy; therefore, we studied 28 patients in NYHA class I and II, characterized by complex ventricular arrhythmias (VA) on 24-h Holter monitoring and volumetric and/or contractile abnormalities on a standard two-dimensional echocardiogram (2-D echo). All patients underwent radioisotopic angiography, 20 patients complete hemodynamic study, and 15 patients endomyocardial biopsy. Ambulatory ECG monitoring showed the presence of frequent premature ventricular contractions in 14 patients (50%) and episodes of ventricular tachycardia in 16 patients (57%). 2-D echo showed mono- or biventricular enlargement and dyssynergies in 25 patients (89%) (left ventricle in 6, right ventricle in 11, both in 8). Two patients showed only left ventricle enlargement and one patient isolated left ventricular dyssynergies. Radioisotopic angiography showed mono- or biventricular ejection fraction reduction in 24 patients (85%) and regional dyssynergies in 24 patients (85%) in accordance with 2-D echo. Hemodynamic study showed in all patients normal coronary arteries, and right and left angiography confirmed enlargement and/or regional dyssynergies. Endomyocardial biopsy was abnormal in 11 of 15 patients: various degrees of hypertrophy, parcellar fibrosis, and adipogenic infiltration were found. Our preliminary data suggest that the simultaneous occurrence of ventricular arrhythmias and ventricular dyssynergies and/or enlargement in patients without apparent clinical heart disease may represent an early stage of dilated cardiomyopathy. PMID- 1499179 TI - Anatomy, histology, and pathology of coronary arteries: a review relevant to new interventional and imaging techniques--Part II. AB - In the last 15 years, intense interest has focused on various interventional, pharmacologic, and mechanical forms of therapy for the treatment of atherosclerotic coronary artery disease. Many techniques and devices (dilating balloons, perfusion catheters, thermal probes and balloons, lasers, atherectomy devices, stents, intravascular ultrasound) have been used or are under study for future use. Many of these techniques and devices require an understanding of histologic and pathologic features of the coronary arteries and diseases which affect them. This article reviews selective areas of anatomy, histology, and pathology relevant to the use of various new interventional techniques. Part II of this four-part review will focus on aging changes seen in the epicardial coronary arteries and will review selected features of atherosclerotic plaque, including fissure and topography. PMID- 1499180 TI - Acoustic appearance of atrial septal aneurysm. AB - Atrial septal aneurysm in the otherwise normal heart is a very rare and usually asymptomatic condition. A midsystolic click was described as the only clinical manifestation so far. A low-pitched early-to-midsystolic acoustic phenomenon in a 39-year-old woman corresponding with maximal leftward motion of the aneurysmatic interatrial septum during early systole is the subject of this case report. Our experience, plus review of the literature, supports the suggestion that atrial septal aneurysm should be considered in the interpretation of added systolic sounds. PMID- 1499181 TI - Massive main pulmonary artery embolism diagnosed with two-dimensional Doppler echocardiography. AB - This report describes the usefulness of echocardiography in the differential diagnosis of acute cardiovascular events. In a 66-year-old patient with known aortic stenosis and mitral valve prosthesis, who suddenly deteriorated with severe dyspnea, a thrombus within the pulmonary artery could be detected with 2-D echo. Pulsed-wave Doppler disclosed the resulting flow-velocity disturbances. PMID- 1499182 TI - Werner Forssmann: a German problem with the Nobel Prize. PMID- 1499183 TI - Stunning, hibernating, now preconditioning. PMID- 1499184 TI - Magnesium disorders and cardiovascular diseases. PMID- 1499185 TI - Prognosis for patients with initially suspected acute myocardial infarction in relation to presence of chest pain. AB - In all 4,232 patients admitted to a single hospital during a 21-month period due to initially suspected acute myocardial infarction (AMI), the prognosis and risk factor pattern were related to whether patients had chest pain or not. Symptoms other than chest pain that raised a suspicion of AMI were mainly acute heart failure, arrhythmia, and loss of consciousness. In 377 patients (9%) symptoms other than chest pain raised an initial suspicion of AMI. These patients developed a confirmed infarction during the first three days in hospital with a similar frequency (22%) as compared with patients having chest pain (22%). However, patients with "other symptoms" had a one-year mortality of 28% versus 15% for chest pain patients (p less than 0.001). Patients with "other symptoms" more often died in association with ventricular fibrillation and less often in association with cardiogenic shock as compared with chest pain patients. Among the 921 patients who developed early AMI, 64 (7%) had symptoms other than chest pain. They had a one-year mortality of 48% versus 27% for chest pain patients (p less than 0.001). We conclude that in a nonselected group of patients hospitalized due to suspected AMI, those with symptoms other than chest pain have a one-year mortality, which is nearly twice that of patients with chest pain. PMID- 1499186 TI - Left ventricular diastolic dysfunction in coronary artery disease: effects of coronary revascularization. AB - Left ventricular diastolic dysfunction was studied globally and regionally in patients with coronary artery disease, and the effects of coronary revascularization were evaluated. A total of 25 patients with angina pectoris who had a stenotic lesion (greater than or equal to 90%) in only left anterior descending branch underwent coronary revascularization [percutaneous transluminal coronary angioplasty (PTCA) in 13 patients and coronary artery bypass graft (CABG) in 12]. Nine patients with normal coronary artery were studied as controls. Left ventricular volume and radial axes were measured on serial frames of one cardiac cycle by cine left ventriculography. The radial axes were drawn from the left ventricular gravity to left ventricular wall at every 20 degrees. Left ventricular filling fraction and distension rate of radial axes were calculated at the times of 25%, 50%, 75%, and 100% of diastolic period, 100% being end-diastole. Although there were no significant changes of the systolic function by revascularization, the filling fraction increased from 11.2 +/- 2.6 to 14.5 +/- 3.5% (p less than 0.001) at 25% time of diastole, from 29.9 +/- 4.9 to 32.5 +/- 5.0% (p less than 0.05) at 50% time in the PTCA group, and from 11.8 +/- 3.7 to 13.4 +/- 3.8% (p less than 0.01) at 25% time in the CABG group. The distension rate of radial axis to the anterior wall also increased significantly at 25% and 50% time of diastole after revascularization, and the change was marked in the PTCA group. However, these increases did not apply to the control patients.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1499187 TI - Exercise echocardiography after stabilization of unstable angina: correlation with exercise thallium-201 single photon emission computed tomography. AB - The diagnostic usefulness of predischarge exercise echocardiography in 35 patients with unstable angina who responded to medical therapy was correlated with exercise thallium-201 single photon emission computed tomography (TI-SPECT) performed, on the average, three days after the exercise echocardiography. None of the patients had myocardial infarction prior to hospitalization or before TI SPECT and none had left bundle-branch block on their rest electrocardiogram (ECG). Exercise echocardiography was positive in 21 patients and TI-SPECT in 24. The results of the two techniques were concordant in 28 of 35 patients (agreement = 80%, k = 0.57 +/- 0.14, p less than 0.001). Wall-by-wall comparison of the distribution of exercise-induced wall motion abnormalities with reversible thallium defects showed complete or partial correlation in all of 19 patients in whom both the tests were positive. A positive exercise ECG and positive exercise echocardiography identified 11 of 11 patients with angiographically verified significant coronary artery disease (CAD) and 11 of 12 patients (92%) with positive TI-SPECT. Thus, exercise echocardiography is a valuable addition to routine predischarge exercise test in the noninvasive diagnosis of myocardial ischemia and shows a good correlation with TI-SPECT in detecting and localizing ischemia in patients with unstable angina stabilized on medical therapy. PMID- 1499188 TI - Hemodynamic findings during exercise on a bicycle ergometer following balloon valvuloplasty of pulmonary stenosis in children and adolescents. AB - Eleven patients (4 female, 7 male), age range 3.3 to 24.8 years (mean 11.10 years) treated for isolated pulmonary stenosis underwent cardiac catheterization and percutaneous transluminal balloon valvuloplasty (PTVP). The right ventricular systolic pressure (RVSP) before valvuloplasty ranged from 31 to 127 mmHg (mean 79 mmHg) decreasing to 28 to 62 mmHg (mean 42 mmHg) immediately after the dilatation. The peak systolic gradient of the pulmonary valve (delta p RV-PA) before valvuloplasty ranged from 22 to 107 mmHg (mean 61 mmHg) and decreased to a range of 14 and 45 mmHg (mean 23 mmHg) immediately after the dilatation. Balloon valvuloplasty was performed using balloons of 13 to 31 mm in diameter. On 11 patients cardiac catheterization and Doppler echocardiography were repeated between 11 months and 5.3 years (mean 3.11 years) after the balloon valvuloplasty showed a further significant fall in the gradient of pressure. The right ventricular systolic pressure ranged from 20 to 51 mmHg (mean 31.7 mmHg) while the transpulmonary gradient varied from 3 to 24 mmHg (mean 11.6 mmHg). At the time of follow-up examination the patients were aged between 7.2 and 25.7 years (mean 15.9 years). On average the second catheterization was performed 3.11 years following the first hemodynamic study. The follow-up examination encompassed clinical examination, electrocardiogram, Doppler echocardiography, and right heart cardiac catheterization. During right heart cardiac catheterization the children exercised on a bicycle ergometer for three min at 50 or 100 W depending on their body surface area. During this exertion, pressures of the right ventricle and the pulmonary artery as well as heart rate and oxygen saturation were recorded.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1499189 TI - Benefits of the advances in cardiac pacemaker technology. AB - Pacemaker technology has expanded rapidly in the last thirty years. Each phase of development has been marked by both improvements in clinical benefit and disadvantageous interactions of physiology and technology. Each phase of development has led to smaller, more reliable devices with greater programmability. Advances in generator technology and battery design have increased longevity of devices. The first devices used asynchronous pacing which had a significant effect in reducing the mortality of surgically induced complete heart block. Ventricular demand pacemakers overcame the problems of asynchronous competitive pacing, but exposed the pacemaker syndrome. Atrioventricular sequential pacing restored atrioventricular synchrony, resulting in hemodynamic improvement, but created the phenomenon of pacemaker-mediated tachycardia. Alternative dual chamber modes and algorithms have largely resolved this. Adaptive-rate devices have been of benefit to patients with chronotropic incompetence, and are now incorporating an increasing variety of biosensors. Almost all the problems of pacing have been overcome, but the increasing complexity of pacemaker technology is now a major limitation to its proper use. PMID- 1499190 TI - Anatomy, histology, and pathology of coronary arteries: a review relevant to new interventional and imaging techniques--Part III. AB - In the last 15 years, intense interest has focused on various interventional, pharmacologic, and mechanical forms of therapy for the treatment of atherosclerotic coronary artery disease. Many techniques and devices (dilating balloons, perfusion catheters, thermal probes and balloons, lasers, atherectomy devices, stents, intravascular ultrasound) have been used or are under study for future use. Many of these techniques and devices require an understanding of histologic and pathologic features of the coronary arteries and diseases which affect them. This article reviews selective areas of anatomy, histology, and pathology relevant to the use of various new interventional techniques. Part III of this four-part review focuses on eccentric and concentric plaques, formation of coronary thrombus, and status of the "infarct artery" after mechanical and pharmacologic forms of acute reperfusion therapy. PMID- 1499191 TI - A case of neurofibromatosis associated with a coronary artery aneurysm and myocardial infarction. AB - Aneurysms of the aorta, vertebral arteries, carotid artery, thyrocervical trunk, and mesenteric and celiac arteries have been described in patients with neurofibromatosis. These aneurysms may have part of the vessel wall replaced by neurofibromatosis tissue. One previous case reports a coronary artery aneurysm in a patient with neurofibromatosis who suffered a myocardial infarction due to thrombosis formation within the aneurysm. We document a second case of aneurysmal dilatation of a coronary artery in a patient with neurofibromatosis. This patient also had a myocardial infarction in a vascular distribution not involved by the aneurysm. The vascular changes associated with neurofibromatosis are reviewed. Aneurysmal dilatation of the coronary arteries may be a further vascular manifestation of this condition. PMID- 1499192 TI - Caleb Hillier Parry. PMID- 1499193 TI - Total hip arthroplasty in patients 80 years of age and older. AB - One hundred fifty-seven consecutive patients (162 total hip arthroplasties) 80 years of age and older were observed for one year after total hip arthroplasty (THA). Clinical results and complications were recorded. The indication for surgery was degenerative joint disease (DJD) in one half of the patients and complications to proximal femoral fractures in the other half. The mean age was 83 years old in both groups. In 80% of the patients, no complications were recorded during the first year. Three patients died during the first three months. Two deep infections occurred (1.2%). The dislocation rate was 9.2% (15/162). There was a lower dislocation rate (4/84) in the DJD group compared to the fracture group (11/78). All nine recurrent dislocations occurred in the fracture group and were treated with either trochanteric osteotomy (five) or removal of the prosthesis (four). In the patients operated on with trochanteric osteotomy, no further dislocations occurred. The mean hospital stay was 13 days. After one year, 88% (112/127) of the patients who could be observed had good or excellent results. Total hip arthroplasty in the elderly is a reasonably safe method and yields good functional results. Dislocations, however, were common in patients operated on for complications from proximal femoral fractures, and the risk for recurrent dislocation was high (9/11). In these patients, trochanteric osteotomy is recommended. PMID- 1499194 TI - Femoral head intramedullary stemmed implant. A historical prospective. AB - A historical review reveals that McBride may have been the first to use a femoral head intramedullary stemmed hip implant. It had a threaded stem and limited use. Eicher may have been the first to develop and use the smooth intramedullary stemmed femoral implant with a calcar collar, which was the forerunner of implants used today. Moore subsequently developed the self-locking intramedullary stemmed femoral implant with a calcar collar. Shortly thereafter, Thompson introduced a similar prosthesis. These four surgeons pioneered the development of the intramedullary stemmed femoral head prosthesis, which has been a key contribution to modern hip reconstruction. PMID- 1499195 TI - Manifestations of ischemic necrosis complicating developmental hip dysplasia. AB - Ischemic or avascular necrosis of the hip is a serious complication of the treatment of developmental hip dysplasia. The degree of ischemic insult can be classified based on an understanding of the vascularity of the proximal femur. Physeal involvement and subsequent growth disturbance, producing late deformity of the proximal femur, can compromise long-term results. Early recognition of ischemic necrosis patterns can be helpful in planning further treatment. PMID- 1499196 TI - Bead loosening from a porous-coated acetabular component. A follow-up note. AB - Beaded porous-coated implants are commonly used in total joint arthroplasty. In this study, the authors extended the follow-up period for the Davey and Harris study of bead loosening in beaded cementless acetabular components. When 56 primary total hip arthroplasties were first reviewed, at an average of 2.5 years after surgery, the incidence of bead loosening was 8.9%. Reevaluation at a mean of 4.5 years after surgery revealed that the incidence of loosening had increased to 19.6%. Bead loosening was associated with acetabular migration in one component and a broken screw in a second. In the absence of loose beads, there were no broken fixation screws or socket migration. Radiolucencies at the bone implant interface were seen in association with loose beads in only one case. Although long-term implications of bead loosening are not clear, bead migration may increase the possibility of macrophage response to metallic debris. PMID- 1499197 TI - Slipped capital femoral epiphysis. The case for internal fixation in situ. AB - The traditional method of treating slipped capital femoral epiphysis by in situ pinning is being challenged. The complication of chondrolysis has been correlated with unrecognized pin penetration into the hip joint. Several studies have shown that black children may be more susceptible to developing chondrolysis. Fifty five children (89% black) with 80 slipped epiphyses agreed to return for evaluation by the authors at an average of 3.3 years after in situ pinning. The results were classified according to clinical and roentgenographic parameters. The results were excellent or good in 56 (70%) of the 80 slips. Excellent or good results were found in 86% of mild slips, 55% of moderate, and 27% of severe. The complication of chondrolysis developed in three slips (4%) and avascular necrosis in two (3%). Poor pin position could be correlated with the complication in one of the three patients who developed chondrolysis and in both who developed avascular necrosis. Poor pin position was also associated with 12 (60%) of the 20 poor results. The majority of pin problems were secondary to technical problems associated with attempting in situ pinning from the lateral approach. In this study, black children were not more susceptible to chondrolysis than nonblack children. PMID- 1499198 TI - Acute septic arthritis of the hip joint in infancy and childhood. AB - Forty-three children with 45 hip joint infections were admitted to the hospital between 1983 and 1988. The duration of symptoms was the single most important prognostic feature. Almost all children who were treated within four days of symptoms had a satisfactory outcome. Concomitant osteomyelitis of the proximal femur produced by far a worse prognosis than if the infection was confined to the synovium of the hip joint. In addition, patients whose hips were infected with Staphylococcus aureus bacteria were more likely to have a poor prognosis than those whose hips were infected with non-S. aureus bacteria. PMID- 1499199 TI - The Clayton total hip arthroplasty. A ten-year follow-up study. AB - Early success has been reported using a long-stem cemented femoral component in total hip arthroplasty (THA). The same patient group reported by the authors' institution at five years were reviewed again at ten years postarthroplasty. Certain trends can now be defined, including gradual deterioration in the Harris hip score, tendency toward failure of acetabular fixation (8.4% loosening rate requiring revision), and increased calcar resorption. Overall, the cemented femoral component has performed admirably, with a 97% success rate at ten-years' post-THA (3.1% revision rate). In this study, success was defined as arthroplasties that did not require revision. Ninety percent of observed patients were rated as good or excellent using the Harris hip score. The Clayton femoral component provides excellent durability by virtue of design. PMID- 1499200 TI - Stress fracture of the hip. An unusual complication of total knee arthroplasty. AB - Stress fracture of the hip is a rare complication of total knee arthroplasty (TKA). Only eight cases seem to have been reported in the literature. A ninth case is reported in the present study. A 76-year-old obese woman was treated by right TKA for osteoarthrosis with cementing of the tibial component because of insufficient primary fixation. One year after TKA, she complained of tenderness above the right adductor tendons. There was no history of trauma. One month later, bone scintigrams and roentgenograms demonstrated a stress fracture of the femoral neck. Conservative management was successful. Etiologic factors such as rheumatoid arthritis, osteoporosis, steroid medication, or changes in static or dynamic forces of the hip secondary to knee arthroplasty could not be demonstrated in this patient. The increase in activity after TKA may be a factor in the incidence of these stress fractures of the hip. Radionuclear-type bone scan is helpful in diagnosis. The foci of increased isotope uptake are not always seen at the site of the stress fracture and only later visualized by roentgenograms. PMID- 1499201 TI - Total hip arthroplasty in patients with avascular necrosis of the hip. Follow-up observations on cementless and cemented operations. AB - Thirty-one patients with avascular necrosis of the hip were treated by 34 total hip arthroplasties (THAs). All patients were observed prospectively with a minimum two-year follow-up evaluation (average, 46 months; range, 24-84 months). Twenty had cemented arthroplasties using contemporary cementing techniques. This included insertion of a medullary plug, cleansing of the canal with a medullary brush, pulsatile lavage irrigation, and insertion of the cement with a cement gun. In 14 hips, a cementless prosthesis was used. Patients were rated using a modified Harris hip score. Sequential postoperative roentgenograms were analyzed in each patient. The overall Harris hip score ratings were 88 in the cemented and 84 in the noncemented groups. Mechanical failure with loosening of the femoral component occurred in one patient who developed deep sepsis. Significant thigh pain occurred in four patients in the noncemented group. Previous studies in the literature have generally reported unfavorable results in patients with avascular necrosis of the hip treated with THA. Using cementless and cemented fixation with contemporary cementing techniques, improved results can be expected. A high incidence of thigh pain (29%) in the cementless group remains a problem. PMID- 1499202 TI - The late course of acute partial anterior cruciate ligament tears. A nine to 15 year follow-up evaluation. AB - Twenty-two patients had an acute anterior cruciate ligament (ACL) tear. Nineteen patients were treated conservatively, except for associated injuries. In three patients, a reinsertion of the torn portion of the ACL was done surgically. All patients were reexamined after nine to 15 years with special emphasis on stability testing; this was done manually and with instruments. Knee function score and activity level were also measured. Standing roentgenograms with the knee in slight flexion were taken as well. At follow-up examination, none of the patients had needed ACL reconstruction. Knee function was good, with a mean Lysholm score of 93 points. Patients had changed activities from recreational team sports to light individual sports. Manual laxity values were similar to the values obtained at the time of initial injury. A 1-mm sagittal laxity increase was found on the injured knee with the Stryker laxity tester. Slight signs for osteoarthrosis were found in more than half of the knees, mainly in cases with chondral fractures or meniscectomy. In general, conservative treatment had a good long-term prognosis. PMID- 1499203 TI - The lateral trochlear sign. Femoral trochlear dysplasia as seen on a lateral view roentgenograph. AB - Dysplasia of the femoral trochlea is easily detected on an axial roentgenogram of the patellofemoral joint. A roentgenographic sign is described wherein severe trochlear dysplasia can also be readily appreciated on a plain lateral roentgenogram. The subchondral bone of the trochlea is normally seen as a dense white line, which remains parallel to the subchondral bone of the lateral femoral condyle. The intersection of those two lines is indicative of severe trochlear dysplasia and has been named "the lateral trochlear sign." PMID- 1499204 TI - The Ilizarov apparatus for treatment of melorheostosis. Case report and review of the literature. AB - Traditional conservative and surgical methods of treatment of melorheostosis, such as manipulations, plaster casts, soft-tissue releases, capsulotomies, and osteotomies cause a high recurrence rate. In a 12-year-old girl, flexion contracture of a knee with limb inequality caused by melorheostosis was corrected successfully with the Ilizarov distraction apparatus. PMID- 1499205 TI - Posterior cruciate condylar total knee arthroplasty. Average 11-year follow-up evaluation. AB - Forty-two total knee arthroplasties (TKAs) of the posterior cruciate condylar design performed from 1975 until 1978 were reviewed. Follow-up evaluations averaged 11 years. There were 21 knees each of osteoarthrosis and rheumatoid arthritis. The average postoperative knee score was 85.4 points. Thirty-nine knees (92.8%) were rated good or excellent, one (2.4%) was judged fair, and two (4.8%) were considered failures. Postoperative flexion averaged 104 degrees. Analysis of osteoarthritic versus rheumatoid arthritic subgroups demonstrated no significant differences in motion, alignment, or knee score. Roentgenographic review demonstrated no cases of femoral or tibial loosening, but one case of patellar component dislodgement was observed. Nonprogressive radiolucent lines were observed in 75% of the cases. Good results can be expected if satisfactory lower-extremity alignment is attained. Posterior cruciate ligament retention has provided a slightly improved postoperative range of motion. Residual problems appear to be centered about the patellofemoral joint. PMID- 1499206 TI - The Attenborough and Gallannaugh knee prostheses for total knee arthroplasty. A comparison and survival analysis. AB - The characteristic feature of the Attenborough knee prosthesis was a stabilizing link rod, designed to act in place of the cruciate ligaments and to supplement the function of the collateral ligaments when damaged by disease. However, the reported long-term results obtained with this prosthesis have not been satisfactory, and survival analysis of 505 arthroplasties in which this prosthesis was used demonstrates a cumulative 14-year success rate of only 44.9%. In 1982, a new design incorporating the link rod was developed and the results of 149 knees in which this prosthesis was used show a cumulative seven-year success rate of 98.4%, compared with 70.1% in the Attenborough series. The clinical results of the Gallannaugh series are presented in this study. Knee function has been separated from patient activity, the patients being categorized in groups according to their physical state. Thus, the result of the knee operation can be assessed even in those disabled by age and infirmity. The Gallannaugh prosthesis is of particular value in circumstances where the use of an unconstrained prosthesis would be impractical. PMID- 1499207 TI - Hip sonography--how reliable? Sector scanning versus linear scanning? Dynamic versus static examination? AB - In Europe, the use of ultrasonography has become a routine procedure for the detection of hip dislocations and dysplasias; clinical and historical data alone are not fully reliable. Under the right conditions, ultrasonographic examination of the hip can reliably detect hip joints in need of treatment. Furthermore, results are reproducible without the use of roentgenograms; thus the danger of "overtreatment" can be avoided. The use of sector scanners for examinations of hip joints leads to distortions in the geometry of the picture. As a result, the use of linear transducer is presently indispensable. Thanks to a reference level, static examinations of the hip joint provide us with the possibility of measuring and comparing individual hip joints. With dynamic examinations, we can quantify the data and assess hip stability. In fact, the static and dynamic approaches do not exclude but, rather, complement each other. The ultrasonographic method must be learned from experts. Given the above-mentioned conditions, all developmental abnormalities of the hip can be diagnosed in the first six weeks of life, and healthy hip joints can be clearly distinguished from those requiring follow-up examination. Based on observations on 8530 cases, hip joints of infants at least 4.5 months of age can be successfully treated in a conservative manner. Femoral head necroses have disappeared altogether and the need for later surgery has decreased dramatically. PMID- 1499208 TI - Traumatic disruption of the anterior tibial tendon while cross-country skiing. A case report. AB - Closed spontaneous rupture of the anterior tibial tendon is an uncommon injury that occurs after relatively minor trauma in middle-aged and elderly men. A 72 year-old retired physician sustained a complete anterior tibial tendon rupture while he was skiing cross-country. Direct primary repair of the tendon resulted in satisfactory restoration of muscle strength and return to an active life style. PMID- 1499209 TI - Fibular stress fracture associated with distal tibiofibular synostosis in an athlete. A case report and literature review. AB - A 19-year-old collegiate football player with progressive ankle syndesmosis ossification developed acute localized fibular tenderness. Roentgenograms demonstrated a fibular stress fracture proximal to the superior extent of the ossific mass. Surgical resection of the mass resulted in uneventful fibular healing, with resolution of acute and chronic symptoms. PMID- 1499210 TI - Interlocking intramedullary nails. An improved method of screw placement combining image intensification and laser light. AB - Insertion of distal interlocking screws in femoral nails can be technically demanding and may entail substantial exposure. A method of insertion of femoral interlocking screws that uses a laser guiding system in addition to the standard image intensifier was used in an attempt to improve the accuracy of distal screw placement and to limit radiation exposure. Using this technique, 97% of the distal femoral drill holes attempted were successfully made with the first pass of a drill. Little or no resistance to the drill was met from contacting the femoral nail. Average fluoroscopy time was 0.4 minute. Laser-assisted screw placement requires relatively inexpensive modifications of existing equipment and is easy to master. Compared with the more commonly used freehand method, laser assisted screw placement appears to offer a reduction in the amount of time and radiation exposure required to insert distal interlocking femoral screws. PMID- 1499211 TI - Congenital dislocation of the hip. PMID- 1499212 TI - The segmental tibial fracture. AB - A series of 31 segmental tibial fractures is reported. Eighty-four percent of the patients sustained multiple trauma and 80% of these were open fractures. The series includes treatment with 20 external fixators, seven unreamed intramedullary nails, two casts, and two amputations. Complications included a 48% incidence of elevated compartment pressures necessitating fasciotomy. Despite rapid early decompression, there was a 19% incidence of residual motor and sensory deficit. Other complications observed were a 35% incidence of wound infection, nonunion, and malunion. Eighty-one percent of delayed or nonunions occurred at the distal fracture site. Intramedullary nailing produced the fewest complications. The segmental tibial fracture is at high risk for complications. Close observation of the limb for high compartment pressures is advisable. Treatment for compartment syndrome includes prompt decompression and stabilization of the fracture and, as indicated, intramedullary rods without preliminary reaming. PMID- 1499213 TI - Spine fracture in ochronosis. Report of a case. AB - Ochronosis, the musculoskeletal manifestation of alkaptonuria, primarily involves the larger joints of the body, including the spine. Ankylosis of the thoracolumbar spine leads to progressive loss of flexibility. The case described is that of a 72-year-old man with ochronosis who suffered a hyperextension injury to his spine in a fall, resulting in a fracture through an ankylosed L2-L3 disk space. To the authors' knowledge, this is the first reported fracture of an ankylosed ochronotic spine. PMID- 1499214 TI - Acute gonococcal flexor tenosynovitis in an adolescent male with pharyngitis. A case report and literature review. AB - A 15-year-old boy had acute gonococcal flexor tenosynovitis of the middle finger associated with symptomatic gonococcal pharyngitis. The patient had a history of blunt trauma to the hand. The need for a careful history in any sexually active adolescent is emphasized. Acute flexor tenosynovitis may be the only manifestation of disseminated gonococcal infection. PMID- 1499215 TI - Treatment of acutely infected arthroplasties with incision, drainage, and local antibiotics delivered via an implantable pump. AB - Twelve patients with acutely (symptomatic less than ten weeks) infected arthroplasties were treated with minimal debridement and intraarticular antibiotic, amikacin, delivered via an implantable pump. The infection was suppressed in ten cases. Intraarticular levels of amikacin were obtained in eight cases. These levels ranged from greater than 150 micrograms/ml to 1688 micrograms/ml. The systemic level of amikacin remained below 10 micrograms/ml in all but one case. Duration of hospitalization averaged 19 days. There were no significant toxic side effects to amikacin. PMID- 1499216 TI - Imaging in congenital dislocation and dysplasia of the hip. AB - Selection of imaging techniques in patients with congenital dislocation or dysplasia of the hip (CDH) depends on the age of the child and whether one is seeking diagnostic or management information. Ultrasound is effective in children up to one year of age and should be used in place of most roentgenograms. Arthrography and computed tomography are used when surgery is planned. Magnetic resonance imaging is still being evaluated for diagnosis of CDH. PMID- 1499217 TI - Intragluteal spindle cell hemangioendothelioma. An unusual presentation of a recently described vascular neoplasm. AB - A 40-year-old woman noted a large tumor mass in the left buttock that, on microscopic examination, proved to be a recently described, relatively uncommon spindle cell hemangioendothelioma. This particular neoplasm, which has some features of Kaposi's sarcoma, seems not to have been reported previously in a deep, intramuscular location. PMID- 1499218 TI - Staging and treatment of primary and persistent (recurrent) osteoid osteoma. Evaluation of intraoperative nuclear scanning, tetracycline fluorescence, and tomography. AB - The purposes of this study were (1) to evaluate the various methods of preoperative staging of osteoid osteomas, (2) to compare the different methods of intraoperative localization and excision of the tumor, and (3) to develop a clinical strategy for the treatment of persistent (recurrent) lesions. From 1978 until 1986, 14 consecutive patients had excision of osteoid osteomas. All patients' operative reports, roentgenograms, bone scans, computed tomographic scans and histologic studies were reviewed. With an average follow-up period of 94.5 months, 13 of 14 patients were cured with one operative procedure. One patient required two procedures. No patient developed a recurrence. Eleven of 14 niduses were confirmed on hematoxylin and eosin sections. Computed tomographic scan was the most useful preoperative study in localizing the nidus. It helped determine the surgical approach and the portion of bone to be resected. Intraoperative nuclear scanning (IONS) is a reliable technique in confirming complete removal of the nidus, with no increase in operative time. Intraoperative scanning did not appreciably affect the amount of bone resected. Recurrent tumors can be reliably resected, with a high cure rate, by careful preoperative staging and with use of IONS. PMID- 1499219 TI - Multidisciplinary preoperative assessment and late function in dysvascular amputees. AB - During a three-year period, 95 adults were treated by lower-extremity amputations for peripheral vascular insufficiency. A multidisciplinary team for presurgical evaluation determined all to be potentially independent walkers with a prosthesis. Patients were graded for level of independent walking before amputation and again at a minimum two-year follow-up examination using a seven level functional grading system. Seventy-six of 90 patients (84%) ambulated within one functional level of their preamputation status. This return to preamputation level of function was maintained whether comparing preamputation functional level or surgical amputation level. Prosthetic use increased and the use of walking aids decreased with increased functional ambulation levels, but did not correlate with surgical levels. Peripheral vascular insufficiency patients can maintain walking independence. Multidisciplinary presurgical evaluation helps selection of the amputation level and correct prosthetic limb fitting. PMID- 1499220 TI - Structure, expression, and regulation of the major noncollagenous matrix proteins of bone. AB - The noncollagenous proteins (NCPs) that predominate the bone matrix have recently been the focus of intense investigation because of their potential influence on cell attachment, Ca2+ and hydroxyapatite binding, and the mineralization of bone tissue. With the advent of molecular biology, all of the major NCPs of bone have been cloned and their amino acid sequences completely determined. While each of the proteins has distinct structural properties, some proteins appear to be part of gene families. Examples include the small proteoglycans, decorin and biglycan, as well as the gamma carboxyglutamic acid proteins, such as matrix gla protein and osteocalcin (bone gla protein). Some of the NCPs that are clearly not members of any known gene family still share several common characteristics. One such example of this "convergent evolution" is bone sialoprotein and osteopontin. Both are highly posttranslationally modified glycoproteins that share the cell attachment amino acid sequence RGD (arginine-glycine-aspartic acid), which facilitates the attachment of bone cells in vitro, yet they are clearly not related genetically. Using cDNAs and antisera as probes, the precise temporal localization of NCP expression has been determined, and it has been shown that NCPs are produced in skeletal, and in most cases, nonskeletal tissue as well. This observation implies that the functions of the NCPs are not necessarily limited to bone tissue. Many of the promoters for these genes have been isolated and functional domains determined by a combination of chloramphenicol acetyltransferase assay, gel shift, and footprint analyses. The most extensively studied promoter in the NCP category is osteocalcin, whose sensitivity to 1,25 dihydroxycholecalciferol has been delineated in detail. Future studies on the individual and cooperative activities of the NCPs in bone are likely to involve site-directed mutagenesis of cloned DNA and a combination of in vitro and in vivo functional analyses. PMID- 1499221 TI - Use of the Pavlik harness for hip displacements. When to abandon treatment. AB - Seven hundred twenty congenitally dislocated or subluxated hips in 550 patients less than one year old, treated with the Pavlik harness, were retrospectively reviewed. Overall, 11% of the hips proved irreducible by Pavlik harness treatment, 9% had dysplasia at the end of harness treatment, and 5% developed dysplasia by the age of two years two months (average). Fourteen percent of the hips positive for Ortolani's sign, 6% of the hips positive for Barlow's sign, and 2% of the congenitally subluxated hips required open or closed reduction followed by plaster hip spica immobilization. Avascular necrosis occurred in 0.7% of the hips treated with the Pavlik harness alone. Transient irritability with pain and limited motion of the hip occurred in 1% of the hips. The Pavlik harness is not appropriate for the larger child, most children older than eight months of age, the child in whom the examiner does not get an adequate sense of reduction, the hip that redislocates with the slightest adduction, and the hip that requires excessive flexion to maintain reduction. Pavlik harness treatment should be abandoned in favor of other methods if, after two to four weeks of use, abduction has not improved sufficiently to allow reduction, the hip has not reduced, or the hip remains unstable. PMID- 1499222 TI - Mediators of bone resorption around implants. AB - An important cause of prosthetic loosening is bone resorption that results from the interaction of macrophages with implant surfaces and particulate debris. The mediators involved in this bone resorption were investigated in vitro. Medium conditioned by macrophages interacting with foreign materials was assayed for bone resorption stimulation and inhibition, and for prostaglandin E2 (PGE2). In some experiments, the medium was dialyzed, and in others indomethacin was added. Macrophages were found to release stimulators and inhibitors of bone resorption. The relative amount of these was variable. When macrophages interacted with foreign surfaces, their stimulatory effect was ten times their inhibitory effect. Further activation by phagocytosis caused a further 15-fold increase in stimulation, with no change in inhibition. It is probable that before macrophages encounter foreign materials their stimulatory and inhibitory effects are the same so that they do not cause net bone resorption. Important stimulatory and inhibitory mediators were not dialyzable and so were probably cytokines or possibly collagenase. Prostaglandins were neither important stimulators nor inhibitors. There was only enough PGE2 released to account for 2% of the bone resorption that was stimulated. PMID- 1499223 TI - Evidence for eicosanoids within the reparative front in avascular necrosis of human femoral head. AB - Eicosanoids, including prostaglandins and leukotrienes, are important mediators of inflammation. To observe inflammation after necrosis, the histology and the changes of eicosanoid levels were compared in the subchondral cortex and spongy bone of femoral head of sixteen patients with Ficat III or IV idiopathic avascular necrosis (AVN). Neither inflammatory cells nor elevation of eicosanoid levels were observed in the necrotic subchondral cortex or osteochondral junction, whereas infiltration of lymphocytes and plasma cells, fibrosis, and fat emboli were present in the reparative front of necrotic spongy bone. Biochemical analysis in this region revealed significant increases of prostaglandin E2 (PGE2), 6-keto-prostaglandin F1 alpha (6-keto-PGF1 alpha), thromboxane B2 (TXB2), leukotriene B4 (LTB4), and LTC4. The increased eicosanoids due to initial necrosis become aggravating factors by increasing vascular permeability, which leads to marrow edema and intraosseous hypertension; it ultimately develops into a cycle of inflammation and AVN. PMID- 1499224 TI - The conservative management of congenital dislocation of the hip after walking age. AB - Congenital dislocation of the hip (CDH) is a developmental disorder with a wide spectrum of clinical manifestations. Recent advances in imaging techniques have improved clinicians' understanding and early detection of CDH. Despite recent advances, some children remain undiagnosed until after they reach walking age. PMID- 1499225 TI - The functional method of treatment using a harness with stirrups as the primary method of conservative therapy for infants with congenital dislocation of the hip. 1957. PMID- 1499226 TI - Conservative treatment of congenital dislocation of the hip in the newborn and infant. AB - Five practical questions, concerning which hips should be treated, method of treatment, duration of treatment, treatment failure, and whether pretreatment traction is advised in congenitally dislocated hips, are discussed and answered. All hips positive for Ortolani's sign, hips positive for Barlow's sign, dislocated and irreducible hips, and hips that appear unstable by sonography should be treated. A large number of studies document the safety and effectiveness of early treatment in the Pavlik harness. Treatment may be stopped at six weeks in the newborn and three or four weeks after stability is achieved in children three or four months old at the time of initial treatment. Sonography is helpful in determining when to stop treatment. Hips that fail Pavlik harness treatment are at risk to fail with other types of treatment as well and require a cautious approach. Traction before treatment of congenital dislocation of the hip (CDH) may not be necessary. Recent studies have shown that safe reductions may be performed without preliminary traction. PMID- 1499227 TI - The fetal acetabulum. A histomorphometric study of acetabular anteversion and femoral head coverage. AB - To study the development of the acetabulum in the early fetal period, 39 embryologic specimens were reviewed in detail. Histologic serial sections were made through 47 hips in the transverse plane. Measurements of acetabular anteversion and femoral head coverage revealed that both parameters depend on the exact level of sectioning. However, when measured at the level of the maximum diameter of the femoral head, they did not show significant variation through the embryonic and early fetal stages (six to 20 weeks). This is in contradistinction to the late fetal period. The hip does remain covered during this early fetal period. Congenital dislocation of the hip is not an early developmental condition. This accounts for the absence of any reports of hip dislocations in the first half of gestation. PMID- 1499228 TI - Cause and prevention of osteochondritis in congenital dislocation of the hip. AB - All treatment modalities of congenital displacement of the hip (CDH) bear the risk of ischemic necrosis at the proximal femoral epiphysis. The causes of ischemic necrosis were investigated in a review of the literature and personal experience with CDH patients during the past 30 years. Compression of articular cartilage, caused by an increase in intraarticular pressure, has been implicated as the mechanism of osteochondritis. Muscle spasm, pressure on posterior circumflex vessels, and compromised pericephalic microcirculation in the newborn have been demonstrated to increase intraarticular pressure. The most dangerous causative factors include forced reduction under general anesthesia, spica cast immobilization of the hips in the Lorenz or Lange position, insufficient continuous prereduction traction, and splints or braces that are either too rigid or that force the hip into an extreme position. An intertrochanteric varus osteotomy can also lead to ischemic necrosis when performed at the time of reduction. Preventive measures include sufficient continuous traction, casting in a moderate position, and bracing that allows active movement. None of these measures constitute a guarantee against necrosis, but they will lessen the incidence and severity of involvement. PMID- 1499229 TI - Neonatal screening for hip joint instability. Its clinical and economic relevance. AB - Effort to determine the efficacy of neonatal hip examination began in 1967. During the subsequent 23 years, there have been three analyses of the study's data: (1) a retrospective review reported in 1981, (2) a prospective examination in 1989, and (3) an economic evaluation in 1990. The retrospective review concluded that a neonatal hip screening program effectively screens for acetabular dysplasia, and early treatment seems to alter the outcome of congenital dislocation of the hip. The prospective examination, involving 62 newborns diagnosed as having dislocated or dislocatable hips, established that such cases can be effectively treated from birth with flexion/abduction splints monitored by routine clinical and follow-up examinations. An economic evaluation of the data demonstrated an economic benefit of more than $15,000 Cdn per 1000 infants screened. This study, through these three analyses, presents a compelling argument in favor of a routine, standardized neonatal hip examination. PMID- 1499230 TI - Congenital hip dislocation. Long-range problems, residual signs, and symptoms after successful treatment. AB - In the treatment of congenital dislocation of the hip, reduction must be obtained and maintained to provide the proper stimulus for resumption of normal hip joint growth and development. Subluxation and avascular necrosis must be avoided, as degenerative joint disease is certain to occur. Acetabular dysplasia leads to degenerative joint disease with time, although no roentgenographic parameters are predictive. "Normal" hip joint anatomy may fail to develop, depending on the age of the patient at reduction and the growth potential of the acetabular cartilage. However, as normal anatomy as can be achieved should be restored at the age of maturity. This should provide the best possible mechanical environment to avoid exceeding the pressure tolerance level of the hip joint articular cartilage, thereby avoiding degenerative joint disease. PMID- 1499231 TI - Etiologic factors in congenital displacement of the hip and myelodysplasia. AB - The two prime factors in the mechanism of intrauterine displacement of the hip are mesenchymal tissue abnormalities and mechanical stress placed on the fetal hip joint by the leg-folding mechanism. The somatic changes involve general laxity of the articular ligaments, attributable to either the physiologic effects of progesterone or a genetic trait consisting of familial joint laxity. The ligamentous laxity not only interferes with the folding mechanism of the fetal legs but also influences the torsional effect on the hip joints. This facilitates the displacement of the femoral head over the posterior rim of the acetabulum. The mechanical stress caused by the delay in leg folding also appears to play a role in a genetically determined occult form of myelodysplasia. Its prevalence has already been partially revealed by sensory evoked potential tests. Possibly, a more refined motor evoked potential test might help to explain a large percentage of the idiopathic cases. Thus, many of the etiologic factors in congenital hip displacement, previously considered to be caused by pre- and postnatal environmental influences, may well have genetic origins. These origins may be associated with varying degrees of underlying myelodysplasia. The relatively high incidence of firstborn affected, the ratio of female to male patients, the seasonal incidence of birth, and familial and racial prevalence may prove to be genetically predetermined. PMID- 1499232 TI - Complete posterior sternoclavicular epiphyseal separation. A case report and review of the literature. AB - A review of the literature shows that fractures of the medial clavicular physis rarely occur. Fractures of the medial clavicular physis was diagnosed in a 14 year-old boy. Bony closure of this physis may not be complete until as late as 25 years of age. Complete fracture-separations of this physis, with posterior displacement into the mediastinum, should be included in the differential diagnosis of children and any young adult patients with an apparent posterior sternoclavicular dislocation. PMID- 1499233 TI - Compensatory motion in the upper extremity after elbow arthrodesis. AB - Ten healthy male subjects were asked to complete a series of tasks that represent normal elbow function. They were then fitted with a custom adjustable brace that simulated elbow arthrodesis at 50 degrees, 70 degrees, 90 degrees, and 110 degrees flexion and asked to repeat the tasks. The 3 Space Isotrak system was used to measure shoulder motion; a triaxial wrist goniometer was used to measure wrist compensation; and all subjects were videotaped to qualitatively observe other compensatory motion. Unlike other joints, elbow arthrodesis at any angle results in a significant impairment, since the adjacent shoulder and wrist joints cannot compensate to allow completion of activities. PMID- 1499234 TI - Hip flexion contracture in cerebral palsy. The association between clinical and radiologic measurement methods. AB - Hip flexion contracture was examined in 51 spastic cerebral palsy patients by three clinical methods and two radiologic methods. An extremely low association was found between the clinical and radiologic methods with no particular method, clinical or radiologic, showing a higher association. The method of clinical examination should be chosen by convenience. Radiologic measurements by the methods used did not add useful information. PMID- 1499235 TI - Effects of explanation of treatment procedures on dental fear. AB - Dental fear has been described as anticipation anxiety. This study examined the effectiveness of providing pertinent details of treatment procedures to reduce the level of dental fear for dental checkups, prophylaxis, restoration and extraction in 306 fearful patients. Measurements of pre-treatment and post treatment levels of fear showed a significant reduction in dental fear in all four procedures. Results showed that a better understanding of treatment processes reduced levels of dental fear in fearful patients. PMID- 1499236 TI - Condition of toothbrushes in use: correlation with behavioral and socio-economic factors. AB - Toothbrushes and questionnaires from 94 adult dentate individuals were analyzed. More than 97% of respondents said they brushed their teeth at least once a day, while 48% used more than one toothbrush (such as one at home and another at work). Only 47% said they preferred a soft nylon bristle, while 41% preferred medium and 10% a hard nylon bristle. More than 73% of subjects said they used their brushes for 3 months or longer. Examination of collected brushes by both objective and subjective criteria revealed a wide variation in wear; however, the majority of brushes did not appear to be 'worn-out'. No significant correlation was found between objective wear-index and the educational level of the user, annual household income of the user, or reported time in use of the brush. A significant (p less than 0.01) correlation was found between brush wear-index and the ability of the user to judge toothbrush wear. PMID- 1499237 TI - Tobacco-related attitudes and counseling practices of Iowa dentists. AB - Evidence suggests that dentists' efforts to encourage their patients to stop tobacco use can significantly decrease tobacco-related morbidity and mortality. This study identified attitudes and counseling practices of 1116 Iowa dentists and compared results of a subgroup (N = 55) surveyed in both 1983 and 1989 to note changes in their tobacco-related attitudes and practices. Although only 9% of the dentists from the statewide survey felt counseling their patients on tobacco use was inappropriate, 56% reported they did not routinely ask their new patients about tobacco use. With some frequency 90% of the dentists discussed negative health effects of tobacco, whereas only 64% advised their smokers to quit. In addition, fewer than half made special efforts with pregnant patients or those at high risk for heart disease. The vast majority reported seldom if ever using intervention tools such as pamphlets or referral to cessation programs. Data from the subgroup surveyed in 1983 and 1989 indicated few substantial changes in attitudes and counseling practices. Substantial discrepancies exist between dentists' attitudes and counseling practices. Well-designed programs are needed to help dentists select and implement appropriate interventions. PMID- 1499238 TI - A survey on oral hygiene practices among Malaysian adults. AB - A survey on oral hygiene practices was conducted on 537 dentate adult patients aged 15 years and over. The aim of this study was to investigate the variation in dental behavior with regards to socio-demographic factors, namely age, sex, ethnicity, income, education and occupational status. Patients attending nine randomly selected government dental clinics were interviewed on their daily oral hygiene practices. The majority (89.7%) of the subjects reported that they brushed their teeth, 68% used toothpaste containing fluoride, but only 8.4% flossed their teeth. Generally the younger group had better oral hygiene habits. The higher the socioeconomic status of the adults, the better their toothcleaning practices. Awareness concerning dental floss was low regardless of all the socio demographic variables. It was concluded that there is a need to improve the dental health practices of adults in Malaysia. PMID- 1499239 TI - Effectiveness of steam sterilization on the contents of sharps containers. AB - The purpose of this study was to evaluate the killing effect that treatment in gravity or high-vacuum steam autoclaves had on endospores present on strips or applied to dental needles within 10 types of small sharps containers. Spore strips containing Bacillus stearothermophilus endospores were used, while needles were soiled with an equal number of spores or with spores mixed with blood. Needles were tested capped and uncapped. Strips and needles were autoclaved in empty and 3/4 filled containers placed in several orientations (vents open or closed, upward or on-side). If sterilization was not accomplished within the initial period, additional exposure time was added up to a one hour maximum. Major findings for gravity autoclaves were: 1) strips and needles present in empty containers could, in most cases, be sterilized within 15 minutes when the vents were left open and the containers were placed on-side; 2) spore- and spore plus blood-soiled needles were more difficult to sterilize then were commercial spore strips; 3) capping of needles and the presence of blood did not decrease sterilization efficiency; 4) sterilization in the presence of fill material required additional exposure times and 5) larger containers (greater than 500 ml volume) were more difficult to sterilize than were the smaller (250 ml) ones. All type of open-vented, filled containers could be sterilized within 10 minutes in a high-vacuum autoclave. PMID- 1499240 TI - Effects of a two-phase oil-water mouthwash on halitosis. AB - Many oral microorganisms possess hydrophobic outer surfaces. A two-phase, oil water mouthwash has, therefore, recently been developed to remove such oral microorganisms. The oil phase consists of olive oil and other essential oils. The aqueous phase includes cetylpyridinium chloride, which is a disinfectant that promotes the adhesion of microorganisms to oil droplets. This study determined the effects of this mouthwash on the production of volatile sulfide in vivo and in vitro. Neither rinsing with water nor brushing teeth decreased the concentration of sulfide in mouth air at 3.5 h after treatment. A reduction of only 30% of sulfide was observed when a commercial mouthwash was used. However, this study demonstrated that use of the two-phase mouthwash led to approximately 80% reduction of sulfide. Furthermore, volatile sulfide and 2-ketobutyrate productions from methionine in a saliva putrefaction system were completely inhibited by the two-phase mouthwash; and consumption of methionine was decreased by 65 percent. It is concluded that the two-phase mouthwash strongly inhibits the production of volatile sulfide. PMID- 1499241 TI - Maryland dentists' attitudes regarding tobacco issues. AB - Due to increased national interest in tobacco intervention roles for oral health professionals, a survey of Maryland dentists' attitudes toward tobacco issues was conducted. A convenience sample of 700 members of the Maryland State Dental Association was drawn from the total membership list (N = 2200). A 30% response rate was obtained. Subjects were mailed a twelve-item questionnaire that elicited primarily attitudinal information. Results revealed that 54.3% of the subjects never smoked, 39% formerly smoked and 6.1% currently smoke. Smoking behavior was associated with numerous attitudinal variables including dentistry's role in promoting tobacco-use cessation. Relatively few of the respondents were aware of federal initiatives regarding the oral health professions' roles in intervention. Less than half viewed tobacco-use cessation interventions as a practice builder, yet 82.1% believe cessation advice is the dentist's responsibility. Respondents' interest in obtaining free training in tobacco-use interventions was positive and was significantly related to several attitudinal variables. Dentists in Maryland appear to appreciate their role in tobacco-use interventions at both the clinical and community levels. However, they exhibit ambivalence regarding the economic value of office interventions and the need for formalized training. Maryland dentists also need to be apprised of federal initiatives concerning tobacco use interventions. PMID- 1499242 TI - Blood reflux into cartridges for dental anesthesia: detection in residual solution. AB - The study examines blood reflux into cartridges under infiltration anesthesia. When imitation examination was carried out using Pontamine blue dye solution in 7 kinds of syringes using cartridges, dye reflux was observed in all of them. Dye reflux was observed in all but 1 of 4 kinds of cartridges on the market. The amounts of protein in residual anesthetic solution of cartridges after infiltration anesthesia were quantitatively measured by a dye binding method. Human hemoglobin was also measured by enzyme immunoassay (EIA). The detection rates of protein and human hemoglobin were 26.2% (85/324) and 24.2% (24/99), respectively. Study results show that blood reflux cannot be avoided in the cartridge system so reuse of residual anesthetic solution from cartridges should be prohibited as quickly as possible to avert risk of cross-infection of HB and AIDS virus. PMID- 1499243 TI - Tongue indentations as an indicator of clenching. AB - This study examines the diagnostic efficacy of lateral tongue indentations as an indicator of clenching. A retrospective study of 113 patients (85 active and 28 recall) using radiographic indicators, excessive tooth mobility and self-report by the patient suggests that tongue indentations when present are indicators of clenching and warrant routine examination. PMID- 1499244 TI - High fruit consumption and the periodontal status of farm workers. AB - The results of a study on the periodontal health of orchard and vineyard workers on apple, grape, citrus and mixed-variety fruit farms are presented. Workers on grain farms were used as controls. The only significant differences in the diets of the different groups were the very large amounts of fresh fruits eaten by the fruit-farm workers. The CPITN index was used to record the periodontal status. Healthy periodontal sextants (code 0) were significantly less in the citrus group (P less than 0.05) compared to the other groups. However, this group also showed a significantly (p less than 0.05) lower prevalence of deep periodontal pockets than the other groups. PMID- 1499245 TI - A six-week study comparing the efficacy of a rotary electric toothbrush with a conventional toothbrush. AB - The rotary electric toothbrush, Rota-dent, is often recommended and used as an alternative to the conventional toothbrush. The purpose of this short-term study was to evaluate the effectiveness of the Rota-dent on plaque removal and gingival health in comparison to a conventional toothbrush. Twenty-four subjects were divided into two groups. For 6 weeks one group used the Rota-dent, while the other group used a conventional (Oral-B 40) toothbrush. Plaque and gingival indexes were evaluated each week. Results indicated that the Loe and Silness Gingival Index scores improved significantly for both groups. There was a significant improvement in plaque removal as measured by Turesky modification of the Quigley-Hein Plaque Index for the Rota-dent group, while there were no significant differences in the Silness and Loe Plaque Index for either group. Thus, both devices had a positive effect on gingival health, and the Rota-dent removed plaque better than a conventional toothbrush as measured by one but not another plaque index. PMID- 1499246 TI - Clinical evaluation of the effect of two types of dental floss on plaque and gingival health. AB - The aim of this clinical study was to evaluate two different flosses (an expanded PTFE-type floss and a nylon waxed floss) on the reduction of dental plaque, gingival health (MGI and BI), and patient preference when used in an oral hygiene program. Sixty adult subjects with gingival inflammation were assigned randomly to two groups. The control group were those subjects that used the nylon waxed floss and the test group were those subjects that used the PTFE-type floss. At 0, 2, 5, and 6 weeks, the patients were scored for plaque (PI), gingivitis (MGI), and interproximal bleeding sites (BI). The data were then analyzed statistically within each group and between both groups using Student t tests. It was found that there was no statistical difference between the two types of dental floss regarding PI, MGI, and BI. The only discrepancy was at the end of the second week, where the PTFE-type floss showed a significantly greater reduction in BI as compared to the nylon floss (p less than 0.01). Here the percent reduction of the PTFE-type floss was 56.1%, while the nylon waxed floss showed a percent reduction of only 39.1%. At the fifth week of examination the type of floss used was reversed for one week. This was done to determine patient preference. It was found that 74.5% of the study population preferred the PTFE-type floss while only 24.5% preferred the nylon waxed floss. PMID- 1499247 TI - The oral prophylaxis--survey II. AB - A survey of Wisconsin dentists was done to better understand what procedures dentists are including in their oral prophylaxis or soft-tissue management program. The goal of the survey was to develop data so that suggestions could be made to improve this service. When we compare this survey with the survey done four years ago, we see a decline in quality care, particularly in the time spent doing the oral prophylaxis. There was little or no improvement in recording of periodontal probing depths, sharpening of instruments, use of disclosing solution and the frequency of recall. PMID- 1499248 TI - Inhibition of plaque accumulation under periodontal dressing by sustained-release varnish of chlorhexidine. AB - Slow-release varnish containing chlorhexidine was applied prior to the application of a periodontal dressing. The ability of the slow-release varnish to inhibit accumulation of dental plaque under the dressing was compared to a placebo varnish. Seven volunteers were fitted with periodontal dressing on the lower and upper jaws. One jaw was pre-coated with slow-release varnish containing chlorhexidine, while the other was coated with a placebo. A week later the dressings were removed and the plaque under the dressing was scored. Significantly less plaque was found on teeth pre-coated with the slow-release varnish containing chlorhexidine as compared to the control. An increase in the amount of gingival fluid was observed in both the control and experimental groups after removing the periodontal dressing. PMID- 1499249 TI - Bacterial growth inhibition and short-term clinical efficacy of a vegetable oil based mouthrinse: preliminary study. AB - Bacterial growth of a vegetable oil-based product was determined in vitro. Growth of Streptococcus mutans and Veillonella alcalescens was strongly inhibited for dilutions up to 50x. On the basis of these results, it was decided to evaluate the short-term, clinical efficacy of a 1:10 dilution of the concentrated product in water. Fifteen human volunteers employed this rinse twice-a-day during a six day period. Planimetric plaque scores, as well as the plaque and gingival indexes according to Loe, were assessed at the beginning and end of this period. The efficacy of such a rinse, though less than of chlorhexidine-based products, turned out comparable to several other commercially available products with a reasonable potential in maintaining a low gingival index. PMID- 1499250 TI - Effect of a twice daily 0.12% chlorhexidine rinse on the oral health of a geriatric population. AB - The inhibitory effect of a chlorhexidine rinse on gingival inflammation and plaque accumulation has been well documented. The purpose of this study was to determine whether a twice daily oral rinse with 0.12% chlorhexidine will resolve denture-associated inflammation in a geriatric population. Thirty-six subjects, average age 83 years, were randomly divided into two groups, active and control, and further stratified into three subgroups, removable partial dentures, complete overdentures and lacking a removable prosthesis. Gingival (Loe and Silness '63) and plaque (Silness and Loe '64) indexes were performed on teeth Nos 3, 9, 12, 19, 25 and 28 at baseline and at 60 days. The subjects, following baseline measurements, were required to rinse twice daily for 30 seconds with either a 15 ml solution of 0.12% chlorhexidine or a placebo and instructed to continue their normal oral hygiene routine. The data were statistically analyzed. When active and control groups were compared, either in total or within their stratified subdivisions, significant differences were observed (P less than 0.001). The active group had a 10.27% and 16.68% reduction in the gingival and plaque indexes, respectively, compared to insignificant changes in the control groups. It was concluded that although chlorhexidine proved effective in reducing inflammation and plaque scores, this reduction was not influenced by the type of prosthesis worn. PMID- 1499251 TI - 1992 Colorado Medical Society medical office resource book. PMID- 1499252 TI - A prototype instrument combining laser Doppler flowmetry and reflection pulse oximetry. AB - A prototype instrument has been developed to combine the monitoring techniques of laser Doppler flowmetry and reflection pulse oximetry, both of which depend on laser light backscattered from the skin tissue. Simultaneous and continuous measurements of both microvascular blood flow and blood oxygen saturation were obtained from the same measurement site. Oximetry readings from the combined instrument were calibrated using a model system, and compared with those determined using a Nellcor N-100 transmission pulse oximeter in a limited clinical study: they showed a variability of +4% and read low by 5-10%. PMID- 1499253 TI - The development of the low profile Liverpool shear transducer. AB - The development of a shear transducer, small enough to be worn comfortably under a normal foot, is described, along with a microcomputer controlled data logger. Walks up to 8 s can be recorded and the information downloaded to any IBM compatible computer. Software then allows easy analysis of the peak shear stresses. Calibration curves show the transducers to have a linear response up to 35N and preliminary data from the measurement of shear stresses under the normal foot, and their relationship to vertical pressures, is presented. A patent application (number 9109463.1) has been filed for the device in the United Kingdom. PMID- 1499254 TI - Infrared emissivity of burn wounds. AB - Emissivities of burn wounds and tissue samples have been measured in the wavelength range 8-14 microns using a non-contact method. Emissivities of wound tissues studied were in the range 0.976-0.992, greater than those of intact skin by 0.01-0.03. This will result in underestimates of the difference in temperature between wounds and normal skin of 0.1-0.2 degrees C. PMID- 1499255 TI - Measurement and prediction of drug solvent losses by evaporation from a jet nebuliser. AB - The evaporative losses of solvent (water) from a commercial jet nebuliser (Unineb, Unimed Ltd) were estimated and found to be approximately 14% of total nebuliser output. A simple analysis of the nebulisation process then enabled the amount of the drug colomycin released as potentially respirable aerosol to be predicted from measurements of the total nebulisation time. Good agreement was found between the predicted (P) and measured (M) values such that P = 1.07 M (r2 = 0.98). The analysis also indicates that the proportion of the drug released as aerosol will increase as nebulisation proceeds provided nebuliser output is continuous and that for a given initial mass of drug a larger amount of drug is released as an aerosol if the volume of administration used in the nebuliser is as large as possible. PMID- 1499256 TI - Accurate screening for abdominal aortic aneurysm. AB - In Birmingham a screening programme has been set up to detect abdominal aortic aneurysm in the male population between the ages of 65 and 75 years. The men to be screened are invited to their own general practitioners surgery and offered an abdominal ultrasound. The accuracy with which abnormalities can be detected is of crucial importance to a screening programme. Repeatability has been assessed for the single operator involved and is found to be +/- 1.3 mm. The accuracy of a single scan has been calculated by comparison with the measured diameter from a CT scan of the patient, taken subsequently. This comparison indicates that 95% of the differences between the two measurements can be expected to be less than 3.5 mm. PMID- 1499257 TI - Single breath measurement of pulmonary blood flow in man: the causes of variability. AB - Theoretically, pulmonary blood flow can be measured by the uptake of a 'soluble' gas (e.g. freon-22) compared with an 'insoluble' gas (e.g. argon). As with all indirect methods, a number of uncertainties exist. Inhalation of a freon-22 and argon mixture (3.5%, 10%, 35% O2 balance N2) was made, with a subsequent, slow steady exhalation. The complete manoeuvre is termed the single breath technique (SBT). The repeatability of the SBT was assessed over four repeat measurements at rest, the mean difference between paired measurements lying in the range -0.09 to 0.04 l min-1, excluding the first trial measurements. Various features of the SBT were investigated to assess their influence on the reliability of the technique. It is shown: that the initial volume inhaled should be close to vital capacity; that a brief period of apnoea greater than 9 s following inhalation is necessary; that the subsequent exhalation should be about 10 l min-1; and that difficulties associated with recirculation of freon-22 are not encountered, presumably due to its wide distribution in body water. Under these highly controlled circumstances the technique is reliable. PMID- 1499258 TI - High frequency eye tremor: reliability of measurement. AB - Recent reports suggest that high frequency eye tremor or ocular microtremor (OMT) may be a useful indicator of brainstem function. The method of record analysis, and in particular the amount of record subjected to such analysis, has varied widely. We have recorded OMT from 10 normal subjects. Using these records we have performed 42 distinct replication reliability studies. We suggest seven parameters of OMT (including overall frequency of tremor) which may be of value in comparing abnormal with normal records. For each parameter we have determined the optimal duration of the record to analyse and the reliability of such analysis. Our results suggest that at least 5 s of OMT should be analysed to yield an acceptable estimate of all seven parameters. PMID- 1499259 TI - A monitoring device for pressurised-air-driven diaphragm-based artificial heart assist devices. AB - A non-invasive device has been developed to monitor the diaphragm position and the blood flow in artificial heart assist devices equipped with a pressurised-air driven diaphragm. Light scattering from the diaphragm is used as a mechanism for measuring. Information about the position of several points of the diaphragm can be obtained. The completely empty or filled situation can be detected and used for control purposes. Flow data can be extracted and bending characteristics of the diaphragm during operation can be studied. PMID- 1499260 TI - Assessment of oxygen transfer in membrane oxygenators during clinical cardiopulmonary bypass. AB - Although functional replacement of the heart and lungs by a pump and oxygenator is a widespread surgical procedure, no widely accepted technique for describing gas exchange in oxygenators exists. In this study, 8 types of commercially available membrane oxygenator (2 flat sheet membrane, 4 gas in hollow fibre membrane and 2 blood in hollow fibre membrane) have been studied during clinical cardiopulmonary bypass. O2 transfer increased with blood flow rate but the O2 transfer at a given blood flow was lower than that obtained by the manufacturers in laboratory studies. Overall O2 transfer coefficients were calculated from the ratio of O2 transfer rate to an O2 difference expressed either as an O2 partial pressure or an O2 concentration. Specific O2 transfer coefficients (overall coefficient divided by membrane area) were similar for oxygenators with a flat sheet or gas in hollow fibre membrane configuration. The two types of oxygenator with blood in hollow fibre membranes had significantly lower (P less than 0.01) specific O2 transfer coefficients. This study shows that oxygenator gas transfer characteristics can be studied in the clinical environment and that O2 transfer coefficients can be related to oxygenator design features. PMID- 1499261 TI - Identification of chicken (Gallus domesticus) adipocyte plasma membrane and differentiation specific proteins using SDS-PAGE and western blotting. AB - 1. Affinity-purified adipocyte membrane proteins were used to raise antisera in two sheep. 2. Using one of the antisera 15 proteins were identified as being adipocyte specific by comparison on Western blots of plasma membrane proteins from various tissues. 3. Of these 15 proteins eight appeared to be present only in mature adipocytes and not in the adipocyte precursor. 4. In the presence of guinea pig complement the two antisera raised were cytotoxic to adipocytes and their precursors. 5. Characterization and further study of these adipocyte differentiation specific proteins will provide valuable information about the process of adipocyte differentiation. PMID- 1499262 TI - Purification and partial characterization of hyaluronidase from stonefish (Synanceja horrida) venom. AB - 1. A marine hyaluronidase was purified 261-fold from the stonefish (Synanceja horrida) crude venom using Sephacryl S-200 HR and heparin affinity-gel chromatography. 2. Stonefish hyaluronidase has a pI of 9.2, a mol. wt of 62,000 and it was purified to a very high spec. act. of 1.6 x 10(6) NFU/mg protein. 3. It was heat sensitive and was inhibited by Cu2+, Hg2+ and heparin. 4. Stonefish hyaluronidase did not contain any haemorrhagic or lethal activity. 5. The N terminal sequence of stonefish hyaluronidase has been determined to be A-P-S-X-D E-G-N-K-K-A-D-N-L-L-V-K-K-I-N. PMID- 1499263 TI - Antibacterial activity inducible in the haemolymph of the silkworm, Bombyx mori, by injection of formalin-treated Escherichia coli K-12 during the fifth larval instar and pharate adult development. AB - 1. Antibacterial activity inducible in the haemolymph of the silkworm, Bombyx mori, by immunization, i.e. by injection of formalin-treated Escherichia coli (E. coli) K-12 during the fifth larval instar and pharate adult development that was reared aseptically on an artificial diet was determined by inhibition zone assay using the same bacterium as a test organism. 2. A peak of antibacterial activity was observed in each development stage; approximately 8 mm in diameter of a clear zone at days 3 or 4 in the fifth larval instar and approximately 5 mm at day 1 in the pharate adults. 3. Acid polyacrylamide gel electrophoresis of immunized haemolymph followed by overlay assay showed that an activity band was associated with two peptide bands that were similar to the cecropin-like peptides A and B that were reported in the silkworm (Morishima et al., 1988, Agri. Biol. Chem. 52, 929-934). Any other activity bands were not observed. No activity band was detectable from the haemolymph of non-immunized insects. 4. Fractionation of antibacterial peptides in immunized haemolymph on a CM-cellulose column resulted in separation of two groups of activity, both in the fifth instar larvae and in the pharate adults with a slight difference in elution conditions. 5. Duration of high antibacterial activity induced by a single immunization was approximately 12 hr in the fifth instar day 3 larvae and 48 hr in the day 2 pharate adults. PMID- 1499264 TI - Regulation of intracellular protein degradation in the isolated perfused liver of the chicken (Gallus domesticus). AB - 1. The effects of insulin, glucagon and a supply of exogenous amino acids on protein degradation have been studied in isolated perfused livers from growing chickens by measuring the rate of net valine release in the presence of cycloheximide. 2. Insulin inhibited protein degradation as did a supply of exogenous amino acids. 3. Addition of glucagon increased uric acid release from the livers but had no significant effect on protein degradation. 4. When the effects of the hormones and amino acid mixture are compared with published data for the rat it is evident that the action of glucagon differs in the two species. PMID- 1499265 TI - Induction of antibacterial activity in the haemolymph of the silkworm, Bombyx mori, by injection of formalin-treated Escherichia coli K-12 in the anterior and posterior body part of the ligated larvae. AB - 1. Induction of antibacterial activity was investigated in the ligated fifth instar larvae of the silkworm, Bombyx mori, by injection of formalin-treated Escherichia coli K-12 into the haemocoel in the anterior and in the posterior body part, followed by activity determination by inhibition zone assay of the haemolymph at 12 and 24 hr after immunization. 2. At 12 hr after immunization, high antibacterial activity, approximately 6.8-7.5 mm in the anterior body part and 4.5-6.4 mm in the posterior body part in diameter of a clear zone (2.0 mm for no activity) was detectable in day 3 larvae. This result was in good contrast to expression of lectin gene in the ligated flesh fly, Sarcophaga peregrena (Shiraishi and Natori, 1988, FEBS Lett. 232, 163-166), in which only the anterior part of insect responded to stimulus of injury. 3. Antibacterial activity at 24 hr after immunization in days 3 or 4 ligated larvae was lower than that at 12 hr; 4.0-4.5 mm of activity was observed in the anterior body part, and no activity was observed in day 3 ligated larvae in the posterior body part. 4. Acid polyacrylamide gel electrophoresis of the haemolymph of immunized insects followed by overlay assay showed that the size of antibacterial activity bands were similar between the haemolymph from 12 hr and from 24 hr, and between the anterior and the posterior body part. This result was contradictory to the observation of activity by inhibition zone assay. The activity bands were associated with peptides that were similar to cecropin-like peptides A and B in the silkworm.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1499266 TI - Oral immunization with Escherichia coli K-12 of the fifth instar larvae of the silkworm, Bombyx mori, reared on an artificial diet under completely aseptic conditions. AB - 1. Effect of oral administration of live or formalin-treated Escherichia coli (E. coli) K-12 to the fifth instar, days 1 and 3 larvae of the silkworm, Bombyx mori, on induction of antibacterial activity in the haemolymph was investigated using the silkworms reared on an artificial diet under completely aseptic conditions. 2. When live E. coli was administered to the male day 1 larvae, low but significant antibacterial activity of 3.8 mm was detectable in the haemolymph of one individual at 48 hr after immunization. The proportion of the larvae to express antibacterial activity increased thereafter and at 120 hr after immunization, all three individuals showed antibacterial activity. In day 3 male larvae, activity was detectable at 48 and 72 hr after immunization. 3. When formalin-treated E. coli was orally administered to days 1 and 3 male larvae, no activity was detectable at any time post-immunization. 4. In the second experiment, when day 1 larvae, females and males were orally immunized with live E. coli, only females showed antibacterial activity in the haemolymph, beginning from 24 hr after immunization and up to 96 hr. 5. Removal of an antibiotic, chloramphenicol, from ingredients of an artificial diet was required for induction of antibacterial activity with oral administration of live E. coli. 6. When live E. coli that grows at pH 9.0 was selected and used for oral immunization, antibacterial activity was induced both in females and males at 72 hr after immunization and the activity was observed at 96 hr. 7. These results suggest that establishment of oral immunization with live E. coli in the silkworm larvae requires multiplication of E. coli in the midgut lumen and possibly its colonization on the luminal surface. PMID- 1499267 TI - Structure of extracellular hemoglobin from the brine shrimp Artemia salina. AB - 1. Hemoglobin from the brine shrimp Artemia salina, purified by ultracentrifugation and preparative gel electrophoresis in non-denaturing medium, gave in sodium dodecyl sulfate-polyacrylamide gel electrophoresis a single band corresponding to a polypeptide chain with Mr 150,000. 2. Crosslinking by glutardialdehyde resulted in the appearance of a band corresponding to a molecular mass twice that of a polypeptide chain. 3. Limited trypsinolysis gave eight proteolytic bands corresponding to submultiples 8/9-1/9 of a polypeptide chain. 4. We conclude that a molecule of Artemia hemoglobin is composed of two single polypeptide chain subunits and that each subunit consists of nine structural units roughly equal in size. PMID- 1499268 TI - Urinary proteins in four rodent species. AB - 1. Mean urinary protein concentration levels are significantly higher in male Peromyscus leucopus than females (98.4 and 72.4 mg/dl). 2. Only females showed a significant correlation between weight and urinary protein concentration (r = 0.75 vs r = 0.03). 3. In intraspecific sexual electrophoretic comparisons of P. leucopus and P. maniculatus non-denatured urinary protein, four and two common bands were identified, respectively. Males of both species showed an extra protein band. 4. Four common electrophoretically separable denatured urinary protein bands were observed between 14,200 and 116,000 mol. wt in male and female P. leucopus and female P. gossypinus. Three of the four major protein bands were also found in P. maniculatus. Male Reithrodontomys megalotis pattern showed none of the major bands. PMID- 1499269 TI - Determination and developmental changes in carbonic anhydrase III in swine liver. AB - 1. CA-III was measured by enzyme-immunoassay in the livers of male and female swine aged from the fetus to 5 years old. 2. No sexual dimorphism in porcine liver could be detected at 6 months, but stag showed twice as much as swine of the same age. 3. The concentration of CA-III in the liver increased during development up to 6 months of age, followed by decline due to senescence. PMID- 1499270 TI - Purification and characterization of two forms of soluble NADH cytochrome b5 reductases from human erythrocytes. AB - 1. Two forms of soluble NADH cytochrome b5 reductase were purified from human erythrocytes. Two distinct fractions both having the NADH cytochrome b5 reductase activity eluted from the second DEAE-cellulose column were further purified by ultrafiltration and 5'-ADP-agarose affinity chromatography. 2. The final preparations were purified 9070- and 4808-fold, respectively, over hemolysate. Both reductases exhibited identical electrophoretic patterns when subjected to SDS-PAGE and apparent monomer Mr of each reductase was determined to be 32,000 +/ 1300. 3. Vmax values of reductase II for the various electron acceptors, namely, 2,6-dichlorophenolindophenol, ferricyanide and cytochrome c through cytochrome b5 were found to be 1.9, 1.8 and 2 times higher than those of reductase I. 4. Some differences were noted for reductase I and reductase II fractions. Their elution profiles from a second DEAE-cellulose column were quite different and that suggested that reductase II is more acidic than reductase I. Reductase II was found to be more sensitive to heat treatment than reductase I. PMID- 1499271 TI - Regulation of heme pathway in regenerating mouse liver. AB - 1. delta-Aminolevulinic acid synthetase (ALA-S), rhodanese and microsomal heme oxygenase (MHO), were quantitated in Cl4C induced regenerating mouse liver. 2. Maximal hepatomegalia was observed at 48 hr after i.p. injection of a single dose of the toxin. 3. ALA-S activity decreased on day 2, and then significantly increased (50%) between days 3 and 7, returning afterwards to control values. 4. Cytoplasmic rhodanese, as well as MHO activities, exhibited a clear correlation as compared with the ALA-S activity profile. 5. Porphyrin biosynthesis from precursor delta-aminolevulinic acid (ALA) was significantly increased even after 15 days of intoxication. 6. Present results would indicate that Cl4C is acting in a dual fashion. PMID- 1499273 TI - Biosynthetic studies of marine lipids 36. The origin of common sterol side chains in eleven sponges using [3-3H]-squalene. AB - 1. [3-3H]-Squalene was fed to 11 marine sponges containing a mixture of "common" sterol side chains. All of these sponges possess significant quantities of cholesterol, but their ability to biosynthesize it differs widely. 2. All the sponges possess significant quantities of delta 22 sterols, yet none of them was able to introduce the delta 22 double bond. 22-Dehydro-24-norcholesterol and 24 methyl-22-dehydro-27-norcholesterol side chains also originate from the diet. 3. These sponges biosynthesized between 40 and 80% of their sterols, a typical value being 70%. The remainder is derived from the diet or by modification of dietary sterols. PMID- 1499272 TI - Purification and characterization of two chymotrypsin-like proteases from the pyloric caeca of rainbow trout (Oncorhynchus mykiss). AB - 1. Two chymotrypsins, called chymotrypsin I and II, were purified from the pyloric caeca of rainbow trout, by (NH4)2SO4 fractionation, hydrophobic interaction chromatography (phenyl-Sepharose) and ion-exchange chromatography (DEAE-Sepharose). 2. The approximate molecular weights of chymotrypsin I and II were 28,200 (+/- 1200) and 28,800 (+/- 900), respectively, as determined by SDS PAGE and their isoelectric points were about 5. 3. The pH optima of the enzymes were centered around nine, when assayed for succinyl-L-Ala-L-Ala-L-Pro-L-Phe-p nitroanilide (Suc-AAPF-NA) as substrate and both enzymes were unstable at pH values below 5. 4. The amidase activity of both enzymes increased with temperature up to about 55 degrees C. Chymotrypsin I was found to be more heat stable than chymotrypsin II, an effect most likely explained by stronger calcium binding of the former. 5. The trout chymotrypsins were significantly more active than bovine alpha-chymotrypsin when assayed against Suc-AAPF-NA at 25 degrees C and casein at low temperatures (10-20 degrees C), indicating an adaptation of the activities of the trout chymotrypsins to the habitation temperatures of the fish. PMID- 1499274 TI - Measurement of O6-methylguanine-type adducts in DNA and O6-alkylguanine-DNA alkyltransferase repair activity in normal and neoplastic human tissues. AB - 1. Novel assays based on the use of the suicide repair enzyme O6-alkylguanine-DNA alkyltransferase (AGT) to repair O6-alkylguanine-type adducts in DNA have been used for the analysis of extracts of human biopsy specimens of gastric mucosa, urinary bladder mucosa, colon and circulating lymphocytes. 2. Examination of these extracts revealed no detectable amounts of the precarcinogenic adduct O6 meG. 3. AGT measurements were the same among the normal and the autologous samples of all patients examined, which limits its prognostic value as a tumour marker. 4. AGT measurements from the cancer samples were much higher compared with the measurements of the other two groups which proves that AGT is just a marker of tumour burden. 5. Finally, AGT measurements from lymphocytes show that AGT from normal individuals have about the same value as that from patients suffering from cancer in urinary bladder mucosa and colon, but is much lower than that of patients with cancer in gastric mucosa. PMID- 1499275 TI - Developmental changes of lipogenic enzyme activities and lipogenesis in brown adipose tissue and liver of the rat. AB - 1. Brown adipose tissue (BAT) and liver lipogenesis in vivo estimated by using 3H2O as tracer was very low and did not change significantly between 10 and 20 days after birth. Lipogenesis increased dramatically in both tissues by weaning at 20 days, peaking between 25 and 30 days of age. Since that time the rate of fatty acid synthesis in BAT decreased gradually to reach adult level after 2 months, whereas in the liver there was a sharp decrease of lipogenesis. 2. The activities of fatty acid synthase, citrate cleavage enzyme, malic enzyme and glucose 6-phosphate dehydrogenase essentially followed a similar course of developmental changes as lipogenesis. 3. In contrast to the enzymes listed above NADP-linked isocitrate dehydrogenase remained unaltered over the period studied, whereas lactate and malate dehydrogenases exhibited very high activity at 10 days after birth and from then decreased to reach adult level at the age of about 20 days. 4. The data obtained indicate that no substantial differences could be detected in the developmental pattern of lipogenesis and lipogenic enzyme activities between BAT and liver up to 30 days of age but after this time these processes were not co-ordinated in both tissues. Beyond this time the BAT was characterized by a much higher rate of lipogenesis than the liver. 5. The results are discussed in terms of the nutrient changes and the relationship between thermogenesis and lipogenesis in BAT. PMID- 1499276 TI - Porcine thyroid cytosolic, latent alkaline ribonuclease: resistance to protein denaturants. AB - 1. A ribonuclease isolated from porcine thyroid cytosol using phenol: sodium dodecylsulfate treatment was associated with RNA and identical to latent alkaline ribonuclease. 2. Distribution of activity between aqueous and phenolic phases depended on pH, RNA, and ribonuclease inhibitor. 3. The ribonuclease was totally resistant to urea, guanidinium: HCl, chloroform:isoamyl alcohol, ethanol, heating at 100 degrees C for 10 min or at 80 degrees C plus 100 mM NaCl. It was highly resistant to hydrolysis by proteinase K except in the presence of detergent. 4. The extreme stability and other properties of latent alkaline ribonuclease could be the result of its association with RNA. PMID- 1499277 TI - Effects of several alcohols on glycosidase activities in rat liver and brain. AB - 1. beta-D-Galactosidase, beta-D-glucuronidase and beta-NAc-D-glucosaminidase spec. acts from liver displayed statistically significant differences after treatments with certain alcohols. 2. No statistically significant difference was found for the kinetic parameters (Km and Vmax) of the indicated glycosidase activities. 3. beta-D-Glucuronidase and beta-NAc-D-glucosaminidase spec. acts from brain tissue showed statistically significant differences after treatments with certain alcohols. 4. beta-D-Glucuronidase and beta-NAc-D-glucosaminidase activities from liver showed a statistically significant decrease in the presence of in vitro ethanol. Tolerance effects were not observed. PMID- 1499278 TI - Influence of hypoxanthine and other purines on the lecithin:cholesterol acyltransferase reaction in the plasma of rat and other species. AB - 1. Esterification of radiolabelled cholesterol in the plasma of rat, mouse, pig, ox and, to a lesser extent, guinea pig was partially inhibited by hypoxanthine, xanthine and guanine; esterification in human plasma and in plasma from 12 other vertebrate species was unaffected by purines. 2. Esterification of endogenous cholesterol and the formation of lysolecithin in rat plasma were decreased in the presence of purines indicating that it was the lecithin:cholesterol acyltransferase (LCAT) reaction that was inhibited rather than the isotopic equilibration of labelled cholesterol with the endogenous substrate lipoproteins. 3. Maximum inhibition of the LCAT reaction in rat plasma occurred at 1.4 mM hypoxanthine or xanthine; inhibition was not dependent upon the concentration of LCAT or plasma lipoproteins but increased with the amount of lipoprotein depleted rat plasma (LDRP) present in the incubation mixture. 4. Partial inhibition of the LCAT reaction in rat or mouse plasma by purines had no significant effect on the fatty acyl composition of the cholesteryl esters (CE) formed by LCAT. 5. In the presence of heated rat plasma, LDRP or, to a lesser extent, rat high density lipoproteins (HDL) prepared from heated plasma, the LCAT reaction in human plasma was inhibited by hypoxanthine. 6. Rat HDL and LDRP prepared from plasma pre incubated at 37 degrees C for 4 hr before heating increased and decreased, respectively, the inhibitory effect of hypoxanthine on human plasma LCAT compared with HDL and LDRP prepared from unincubated rat plasma.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1499279 TI - A comparison of highly unsaturated fatty acid levels in wild and farmed eels (Anguilla anguilla). AB - 1. Absolute and relative amounts of eicosapentaneoic acid (EPA) and docohexaenoic acid (DHA) in muscle of eels from four different fish farms were compared with samples from wild eels from two different areas of northern Italy. 2. Farmed eels were richer in DHA and EPA than wild animals. 3. The addition of cod liver oil to the diet of farmed eels led to a significant accumulation of EPA and DHA, but no change in total lipid content. 4. The calculation of two indices related to highly unsaturated fatty acid (HUFA) content (FLQ = fish lipid quality; AI = aterogenic index), indicated the higher nutritional value of farmed vs wild fish. 5. We conclude that farmed eels are an adequate source of fish products for human nutrition and propose use of the above-mentioned indices as an effective means for assessing fish nutritional quality for populations at high risk of chronic degenerative disease. PMID- 1499280 TI - Distributions of polymorphisms among pathways of carbohydrate metabolism in the earthworm Eisenia fetida (Oligochaeta). AB - 1. Activities and genetic banding patterns of 36 isozymes in carbohydrate metabolism were detected by spectrophotometry and starch-gel electrophoresis, respectively, in the earthworm Eisenia fetida. 2. Polymorphisms were not distributed randomly among metabolic pathways, activity levels, or gene copy numbers. 3. In glycolysis and the Krebs cycle, 16% of the loci were polymorphic and polymorphisms occurred only when multiple copies of the loci existed. 4. In other pathways, 45% of the loci were polymorphic and the distribution of polymorphisms was independent of gene copy number. 5. Polymorphisms may affect metabolic phenotypes and natural selection may have led to conserved biochemical activity in glycolysis and the Krebs cycle. PMID- 1499281 TI - Erythrocyte metabolism in two species of bats: common bent-wing bat (Miniopterus schreibersii) and red fruit bat (Pteropus scapulatus). AB - 1. Metabolic intermediates, substrate utilization and enzyme activities were determined in the red blood cells of the common bent-wing bat and the red fruit bat. Standard haematological parameters and oxy-haemoglobin dissociation curves were also determined in both species. 2. The glycolytic rate as measured by lactate production was much higher for all substrates in the bent-wing bats. The activities of the glycolytic enzymes were also much higher in this species. 3. The standard haematological parameters were similar for the two species. The levels of 2,3-diphosphoglycerate (DPG) in the red cells of the fruit bat were nearly twice as high as those in the bent-wing bats. 4. The oxy-haemoglobin dissociation curve for the red fruit bat was located to the right of that for the bent-wing bat and both these curves were located to the right of that normally seen for human blood. 5. Both species of bat show blood characteristics well adapted to carrying the increased oxygen demands of flight. PMID- 1499282 TI - River buffalo (Bubalus bubalis L.) AA phenotype haemoglobins: characterization by immobiline polyacrylamide gel electrophoresis and high performance liquid chromatography and determination of the primary structure of the constitutive chains by mass spectrometry. AB - 1. Polyacrylamide gel electrophoresis in ultra-narrow immobilized pH gradient shifted the "Hb fast" band of AA buffalo phenotype haemoglobin into two components which were named Hb1 and Hb3. 2. Urea/Triton electrophoresis and reversed-phase HPLC demonstrated that Hb1 and Hb3 differ in the presence of two structurally distinct alpha chains (alpha 1 and alpha 3), also suggesting that the alpha chains must differ for neutral amino acid substitution. 3. Extensive mass spectrometric analysis on several digests (FAB overlapping) meant to determine the complete sequence of the constituent chains. 4. Two amino acid replacements (Lys 18----His and Asn 116----His) were present in the beta chain with respect to the bovine (A phenotype) chain, whereas the alpha 1 and alpha 3 globins were found to contain four amino acid replacements compared to the bovine alpha, three of which were identical (Glu 23----Asp, Glu 71----Gly and Phe 117--- Cys) and, notably, an insertion of Ala at position 123-124. 5. Furthermore, alpha 1 contains Phe at position 130 whereas alpha 3 contains Ser at position 132 (following the modified numbering as a consequence of the Ala insertion). PMID- 1499283 TI - Structure and possible function of heat-shock proteins in Falciparum malaria. AB - Like many prokaryotes and eukaryotes, the malaria parasite also synthesizes several stress proteins. Most widely studied stress proteins of this parasite are the heat-shock proteins (hsps). Their discovery in malaria is a gift of recombinant DNA technology. Five hsp genes from Plasmodium falciparum have been identified which are located on different chromosomes. Thus the inheritance and expression of hsp genes are independent of each other. They share a large amount of sequence homology at N-terminus with the hsps of other organisms. Their gene regulatory sequences and other elements, important for gene expression, are yet to be determined. The biological role of these proteins in malaria is not fully understood but it is possible that they provide protection to the parasite from various stresses encountered in the host. In this process hsps probably bind to the toxic molecules as well as damaged proteins to flush them out of the parasite. Their involvement in the stage-specific parasite transformation to increase the infectivity and virulence, as observed in other parasites, remains to be determined. Malarial hsps are antigenic in humans. This antigenicity could be attributed to the non-homologous sequences in the C-terminus region. The potential of one of them (pfhsp 70I) for a future malaria vaccine and immunodiagnostics requires re-evaluation of the data. PMID- 1499284 TI - A sulfated proteoglycan from the red alga Gracilaria verrucosa is a hemagglutinin. AB - 1. A novel hemagglutinin was isolated from the red alga Gracilaria verrucosa and characterized as a sulfated proteoglycan with 92% carbohydrate content. 2. It is a dimer (MW 27,000 and MW 23,000); its molecular weight (MW) and isoelectric point are 49,000 and 3.8, respectively. 3. It agglutinates rabbit greater than horse greater than guinea pig greater than goose erythrocytes. 4. This activity is sensitive to heat, but insensitive to protease or periodate. It is not inhibited by simple sugars but by fetuin. 5. Since the periodate treatment of the rabbit erythrocyte lowers agglutination, this hemagglutinin is probably a lectin or a lectin-like molecule with complex saccharide specificity. PMID- 1499285 TI - Isoenzyme studies in one Brazilian and two Venezuelan strains of Schistosoma mansoni. AB - 1. Enzyme polymorphism, analyzed by starch gel electrophoresis, was found to be zero for acid phosphatase, phosphoglucomutase, phosphoglucose isomerase, glucose 6-phosphate dehydrogenase, lactate dehydrogenase, malate dehydrogenase and malic enzyme, in one Brazilian and two Venezuelan strains of Schistosoma mansoni. 2. All loci studied were monomorphic within strains, but the isoenzymic patterns were, however, different among the strains. 3. Results suggest a drastic loss of the genetic variability usually found in natural populations. PMID- 1499286 TI - A soluble calcium-binding protein (SCBP) present in Drosophila melanogaster and Calliphora erythrocephala muscle cells. AB - 1. Soluble calcium binding proteins (SCBP) were isolated from homogenates of whole flies, from the thorax and from muscles of Drosophila melanogaster and Calliphora erythrocephala. 2. Crude preparations were obtained by extraction at low ionic strength, acid and heat treatment. The Drosophila protein was purified by gel filtration, hydrophobic interaction and ion exchange chromatography. In contrast to calmodulin the Drosophila SCBP did not bind to phenyl-Sepharose in a Ca(2+)-dependent way. 3. Both the Drosophila and the Calliphora protein revealed identical properties. 4. The apparent molecular mass of the SCBP is 24 kDa. Separation in urea-PAGE demonstrated the existence of two isoforms. 5. The calcium-binding property was assured by a calcium dependent electrophoretic mobility shift and autoradiography of 45Ca(2+)-incubated Western blots. 6. The proteins are abundant in the thorax and were even detectable in crude extracts of various muscles (leg muscles and the extracoxal depressor). In contrast, in power muscles and in the thoracic ganglion the proteins could not be observed. PMID- 1499287 TI - Purification and characterization of cathepsin H from hepatopancreas of carp Cyprinus carpio. AB - 1. Cathepsin H was purified about 5400-fold from hepatopancreas of carp (Cyprinus carpio) by the method involving ammonium sulfate fractionation, and chromatography on S-Sepharose, DEAE-Sephacel, Ultrogel AcA54, Concanavalin A Sepharose 4B and GPC on Protein-Pak 125. 2. The purified cathepsin H gave a single protein band on analytical-PAGE, but migrated as two bands of 27,000 and 23,000 mol. wt on SDS-PAGE. 3. Cathepsin H had a pH and temperature optimum of 6.5 and 45 degrees C using Arg-MCA as a substrate, respectively, and was activated by sulfhydryl compounds and inhibited by cysteine protease inhibitors and metal compounds having high reactivities at cysteine residue. 4. The carp hepatopancreas cathepsin H immunoreacted with the monospecific antibody against rat liver cathepsin H, and did not react with the antibodies against carp hepatopancreas cathepsins B and L by the method of immunoelectrophoretic blotting. PMID- 1499288 TI - Characterization of the snake venoms from seven Brazilian species of Bothrops by FPLC anion-exchange chromatography. AB - 1. The elution profiles and the caseinolytic, myotoxic, coagulant and hemorrhagic activities of the venoms of seven Bothrops species fractionated on a Mono-Q FPLC column were analyzed. 2. Each venom separated into 16-20 peaks, with good reproducibility and the activities were concentrated in virtually discrete regions of the chromatogram. 3. There is a considerable overlap of active proteins in the different species venoms and our results indicate that a venom pool with the species B. jararaca, B. jararacussu, B. moojeni, B. neuwiedi and B. atrox venoms would contain the major active proteins determined in the seven species. PMID- 1499289 TI - Androgen metabolism in somatic and germinal tissues of the sea star Asterias vulgaris. AB - 1. Cell-free homogenates of male and female pyloric caeca, body wall, testis and ovary were incubated with radiolabeled 3H-androstenedione. 2. Pyloric caeca had highest rates of androstenedione conversion. The predominant metabolites in the pyloric caeca were testosterone, 5 alpha-androstane-3 beta, 17 beta-diol and 5 beta-androstane-3 beta, 17 beta-diol. 3. In body wall, testicular and ovarian homogenates, androstenedione was converted primarily to testosterone and also to 5 alpha-androstanedione and epiandrosterone. 4. Qualitative and quantitative differences in androgen metabolism in somatic and germinal tissues may be related to tissue-specific regulation of cellular metabolism. PMID- 1499290 TI - Isolation of an acute-phase phosphorylcholine-reactive pentraxin from channel catfish (Ictalurus punctatus). AB - 1. Channel catfish (Ictalurus punctatus) serum contains a protein that precipitates pneumococcal C-polysaccharide (CPS) in a calcium-dependent fashion. 2. The serum titer of this protein follows an acute-phase pattern in catfish injected with turpentine. 3. A non-glycosylated, phosphorylcholine (PC)-reactive protein (PRP) with molecular mass ca 100 kDa, was isolated from channel catfish acute-phase sera by affinity chromatography on PC-Sepharose 4B. 4. Contaminating proteins with molecular masses ca 700 kDa and ca 20 kDa that co-eluted with PRP from PC-Sepharose appear to be aggregated and native low-molecular weight factors (LMFs), respectively. 5. Purified PRP has gamma mobility but in serum samples PRP has gamma-beta mobility. 6. Electron microscopy confirmed that PRP has planar, pentagonal symmetry. 7. The amino terminus of PRP is blocked, but based on comparison of amino-acid compositions channel catfish PRP is clearly similar to human CRP and is most like CRPs from the dogfish (Mustelus canis) and rainbow trout (Oncorhynchus mykiss). PMID- 1499291 TI - Chelation affects the conformation, lability and aggregation of channel catfish (Ictalurus punctatus) phosphorylcholine-reactive protein (PRP). AB - 1. Phosphorylcholine-reactive protein (PRP) affinity-purified from channel catfish (Ictalurus punctatus) serum on phosphorylcholine-Sepharose, eluted from Bio-Gel A-5M as a 94.6 +/- 2.4 kDa protein when the gel filtration column buffer (Tris-saline) contained 25mM ethylenediaminetetraacetic acid (EDTA). 2. PRP chelated with EDTA immediately after affinity purification and gel-filtered in Tris-saline-EDTA, eluted as a 75.5 +/- 2.67 kDa protein referred to as fast-PRP (F-PRP). 3. PRP and F-PRP were identical on SDS-PAGE. Both resolved as a broad band of protein (ca 86-100 kDa) on non-reducing gels or as a ca 100 kDa protein after reduction with 2-mercaptoethanol (2-ME). 4. After gel-filtration in Tris saline-EDTA, nearly complete reduction of 100 kDa PRP was achieved on SDS-PAGE. However, the protein regained its resistance to reduction upon storage at -60 degrees C. 5. SDS-PAGE and native PAGE also revealed that during storage, PRP and F-PRP combined to form 3 different aggregates referred to as aggregated-PRP (aggPRP). These aggregates are readily dissociated in the presence of 2-ME, suggesting a covalent interaction between adjacent pentamers comprising decameric aggPRPs. 6. PRP, F-PRP, and aggPRP have similar amino acid compositions. PMID- 1499292 TI - Subcellular fractionation evidence for a putative peroxisome-mitochondrion attachment in the liver of normal and genetically obese (ob/ob and db/db) mice. AB - 1. Liver post-nuclear supernatants (PNS) from several mouse strains were fractionated by zonal centrifugation and fractions analysed by marker-enzyme estimations+electron microscopy. 2. Rate-dependent banding of PNS yielded peroxisome-enriched (PER) and mitochondrion-enriched (MER) regions. 3. Density dependent banding of PER yielded peroxisomes (approximately 1.22 g/ml) well separated from mitochondria (approximately 1.8 g/ml). 4. Density-dependent banding of MER yielded peroxisomes that co-distributed with mitochondria and electron microscopy revealed close proximity of the two organelles. 5. Experiments demonstrated that co-distribution was not due to weak binding of proteins or to agglutination of organelles. 6. The results indicate in vivo attachment of some mitochondria and peroxisomes. PMID- 1499293 TI - Association of monoamine oxidase and malate dehydrogenase with liver peroxisomes of genetically obese (ob/ob and db/db) mice. AB - 1. Liver post-nuclear supernatants (PNS) from genetically obese (ob/ob and db/db), lean (+/?), and albino mice were fractionated by dual centrifugation in B XIV zonal rotors and subcellular fractions were analysed by marker-enzyme estimations and by electron microscopy. 2. Rate-dependent banding of PNS yielded a peroxisome-enriched region (PER) well-separated from mitochondria. 3. Density dependent banding of PER in ob/ob and db/db mice only, yielded purified peroxisomes which were associated with malate dehydrogenase (cytosolic) and monoamine oxidase. 4. Markers for the mitochondrial matrix, intermembrane space and inner membrane compartments were absent from the peroxisomes. 5. The experimental results are interpreted as indicating that peroxisomes of genetically obese mice are either altered so that protein import is imprecise or so that their attachment to mitochondria is more extensive. PMID- 1499294 TI - Plasma lipoprotein cholesterol concentrations in the golden-mantled ground squirrel (Spermophilus lateralis): a comparison between pre-hibernators and hibernators. AB - 1. The concentrations of total cholesterol (free cholesterol plus cholesteryl ester) in the plasma and in two lipoprotein fractions of golden-mantled ground squirrels (Spermophilus lateralis) were measured during pre-hibernation and compared to those values measured during hibernation. 2. Hibernating ground squirrels had significantly higher (P less than 0.005) very low density lipoprotein plus low density lipoprotein cholesterol (VLDL + LDL-C) concentrations than did pre-hibernating ground squirrels. 3. Hibernating squirrels additionally exhibited significantly higher (P less than 0.005) total plasma cholesterol concentration per high density lipoprotein cholesterol concentration (TPC/HDL-C) ratios than did pre-hibernating squirrels. 4. The significant differences in the lipoprotein cholesterol concentrations observed in this study suggest that lipoprotein metabolism in pre-hibernators was significantly different from that in hibernators and was a reflection of the marked biochemical and physiological adjustments these animals must undergo during their transition from pre-hibernation to hibernation. PMID- 1499295 TI - Proline transport by tsetse fly Glossina morsitans flight muscle mitochondria. AB - 1. Proline accumulation by tsetse fly Glossina morsitans flight muscle mitochondria was studied in vitro by the swelling technique and direct measurement of (U-14C) proline. 2. Proline transport was inhibited by the uncharged liposoluble -SH reagent, N-ethylmaleimide but not by ionic reagent, mersalyl, suggesting that the -SH groups involved in the transport of proline are located in a hydrophobic part of the membrane or on the matrix side of the membrane. 3. The kinetic study of proline accumulation revealed saturation kinetics and a high temperature dependence. It gave a Km of 85 microM and a Vmax of 962 pmol/min/mg protein and an activation energy (Ea) of 11 kcal/mol. 4. Certain other amino acids (L-valine, L-alanine, L-methionine, L-phenylalanine, L tryptophan and L-hydroxyproline) significantly stimulated proline uptake. 5. These observations indicate that tsetse fly Glossina morsitans flight muscle mitochondria contain a proline transport mechanism. PMID- 1499296 TI - On the origin of vertebrate-type steroids present in Locusta migratoria: do they originate from the food? AB - 1. This study investigates the origin of vertebrate-type steroids which were reported to be present in Locusta migratoria: are the steroids synthesized by the locust or are they derived from the diet, i.e. grass and rolled oats? 2. It is unlikely that the steroids are synthesized by locust tissues. In vitro incubations of eleven different tissues with labeled pregnenolone or androstenedione did not result in androgen or estrogen synthesis respectively. 3. Steroid synthesis was also not detected when tissues were incubated in the presence of the early precursors cholesterol and isopentenyl pyrophosphate. 4. It is unlikely that the steroids are derived from the diet. Feeding experiments indicate that only low amounts of steroids are capable of crossing the gut-body barrier. 5. Injection of testosterone in the hemolymph also resulted in rapid excretion, instead of storage in tissues. 6. Moreover, radioimmunological measurements indicate that vertebrate-type steroids are absent in the food of locusts. 7. Specificity studies indicate that substances other than vertebrate type steroids are detected by radioimmunoassay in locust tissue extracts. 8. Because vertebrate-type steroids are absent in locust tissues, it can be concluded that vertebrate-type steroids do not have a physiological function in Locusta. PMID- 1499297 TI - Effect of castration and testosterone therapy on harderian gland protein patterns of the golden hamster (Mesocricetus auratus). AB - 1. Sodium dodecyl sulphate 7-12% gradient polyacrylamide gel electrophoresis of male and female hamster Harderian gland whole homogenate shows a clear-cut sexual dimorphism, which consists of the presence of two male-specific glycoproteins (168 and 116 kDa) and two specific female proteins (210 and 190 kDa). 2. In the male, castration causes a significant decrease in the concentration of the two glycoprotein fractions. 3. Replacement therapy with testosterone propionate (T) restores the intact male pattern. PMID- 1499298 TI - Comparative analysis of lipid composition in axenic strains of Blastocystis hominis. AB - 1. Six axenic strains of Blastocystis hominis varied in content of lipids from 12 to 43 pg total lipid/cell. With all strains, phospholipid content was about 39% of total lipids. 2. Neutral lipid fractions of B. hominis were resolved into nine constituents, of which seven were identified tentatively. Sterol esters, principally esters of cholesterol, were the major neutral lipid constituent, accounting for 49-63% of the neutral lipids, and at least 30% of the total lipids. 3. Polar lipids were resolved into eleven constituents, of which nine were identified tentatively. Phosphatidylcholine was the major polar lipid constituent of all strains, accounting for 53-63% of the polar lipids, and about 22% of the total lipids. PMID- 1499299 TI - Different proteins in the hemolymph sera from sarcomatous and healthy soft shell clams, Mya arenaria L. AB - 1. Serum proteins showed quantitative and qualitative differences between sarcomatous and healthy soft shell clams, Mya arenaria L. 2. Total protein concentration was significantly higher in the serum of sarcomatous clams than of healthy clams. 3. According to SDS-PAGE, more serum proteins with more variability distinguished sarcomatous clams from healthy ones. 4. Sarcomatous clams had unique serum proteins of M(r)23,000, 45,000 and 54,000. Healthy clams had unique serum proteins of M(r) 24,000, 103,000 and 105,000. 5. During disease progression, sarcoma-specific proteins appeared while normal proteins disappeared. 6. We propose that some sarcoma-associated proteins may have tumor promoting and/or cytotoxic functions and that some normal proteins which disappear during disease progression may be involved in the humoral defense system. PMID- 1499300 TI - Proteinases of the medicinal leech, Hirudo medicinalis: purification and partial characterization of three enzymes from the digestive tract. AB - 1. Three different proteinases were isolated from intestinal extracts of Hirudo. 2. The action on synthetic substrates and the effect of various inhibitors indicate that one is a trypsin-like enzyme whereas the other two are chymotryptic. 3. This was confirmed by analysing the degradation of the insulin B chain. 4. The relative molecular masses of all enzymes are approximately 35,000 and the isoelectric points 9.03, 9.12 and 9.41, respectively. 5. The specific activities assayed with SAPPNA are very high in comparison with proteinases of other animals. PMID- 1499301 TI - Regulation of oxidative activity and delta psi of liver mitochondria of active and hibernating gophers. The role of phospholipase A2. AB - 1. In the present work the initially lowered oxidase activity of liver mitochondria of hibernating gophers is shown to increase upon Ca(2+)-loading, after freezing-thawing repeated three times and after swelling in a medium containing potassium acetate as well as in a hypotonic sucrose medium. 2. In all cases the inhibition of phospholipase A2 hindered the increase of the oxidase activity of mitochondria. 3. Mitochondria of hibernating gophers have a lowered delta psi in comparison with active animals, which is restored in the hypotonic medium. PMID- 1499302 TI - The heptadecanoic fatty aldehyde--one of the main aldehydes of the far-eastern Bryozoa. AB - 1. The relative content of 16:0, 17:0 and 18:0 fatty aldehydes in the lipids of eight species of the far-eastern Bryozoa was studied. 2. Heptadecanoic aldehyde is one of the main aldehydes in the seven species investigated comprising about 30% of the sum of these main bryozoan aldehydes. 3. We suggest the unusually high relative heptadecanoic aldehyde content in the lipids of Bryozoa may be helpful in settling some problems concerning their system. PMID- 1499303 TI - Spatial representations of words and nonwords. AB - The first two experiments investigated whether the representations of words, besides being unitary, are also spatial in nature. Subjects were required to search for target letters in either five-letter words or five-letter nonwords. They were instructed to press the right-side key for one target and the left-side key for the other target. The center item of the letter string was always at fixation. Targets appeared one at a time, located at the second (left side) or the fourth (right side) position within the letter string. The results showed that: a) responses to targets within words were faster than responses to targets within nonwords (the word-superiority effect); b) responses to compatible stimulus-response pairings were faster than responses to incompatible stimulus response pairings (the spatial compatibility, or, more precisely, the Simon effect); and c) in Experiment 2, left-side targets were responded to faster than right-side targets within nonwords (the left-right scanning effect). It was concluded that representations of both words and nonwords are spatial in nature. Experiment 3 was aimed at testing whether the spatial layout of the representations of words is always along the left-right horizontal dimension, regardless of the topographic transformation of the stimulus. The same words and nonwords used in the previous experiments were shown vertically and the subjects were required to make left-right discriminative responses to upper and lower target letters. The results showed the word-superiority effect but no spatial compatibility effects. It was concluded that the representation of a vertically presented word is vertically arranged. PMID- 1499304 TI - "Fatal familial insomnia": neuropsychological study of a disease with thalamic degeneration. AB - Fatal Familial Insomnia (FFI) is an inherited disease characterized clinically by sleep, autonomic and motor disturbances and pathologically by marked atrophy of the anterior and dorsomedial nuclei of the thalamus. The neuropsychological study of three cases of FFI showed: (1) a progressive disturbance of attention and vigilance, (2) a memory deficit with lability of mnesic traces and difficulty in manipulation and ordering of events, suggesting an alteration of working memory and (3) a deficit of frontal abilities with impairment in planning and prevision of events but preservation of general intelligence. PMID- 1499305 TI - Everyday memory after unilateral temporal lobectomy or amygdalo-hippocampectomy. AB - Patients who had undergone unilateral temporal lobe surgery (right or left temporal lobectomy or amygdalo-hippocampectomy) for intractable temporal lobe epilepsy, and normal control subjects, completed two questionnaires about everyday memory, the Subjective Memory Questionnaire (SMQ) and the Everyday Memory Questionnaire (EMQ). Relatives/close friends completed suitably adapted versions of these questionnaires about the patient. Patients who had undergone right and left temporal lobectomy rated themselves, and were rated by relatives/friends as having worse memories than controls on both the SMQ and EMQ. Individual items on both questionnaires differentiated between the memory abilities of the five groups. Age at surgery was correlated with one measure of everyday memory for the right temporal lobectomy group, and seizure frequency was correlated with memory performance for the amygdalo-hippocampectomy groups. Issues concerning validity and accuracy of rating memory lapses are discussed. PMID- 1499306 TI - Partial remission of hemiplegia and somatoparaphrenia through vestibular stimulation in a case of unilateral neglect. AB - In a case of long lasting severe neglect resulting from a large right parieto temporo-occipital infarct, vestibular stimulation produced a temporary reduction of the motor deficit and disappearance of the somatoparaphrenic delusion, in addition to the already reported improvement of extrapersonal and personal neglect and anosognosia. These data open new perspectives in the understanding of the neglect syndrome and of functional involvement of the parietal lobe in space representation. PMID- 1499307 TI - Linguistic perseveration in dominant-side intracarotid amobarbital tests. AB - 148 patients with medically intractable complex-partial seizures received bilateral intracarotid amobarbital tests. In 21 patients (14.2%), there were inappropriate responses (intrusions: N = 10; perseverations: N = 11) to a series repetition task (counting backwards) given immediately before amobarbital injection. Five cases from the perseveration subgroup are discussed in detail. In these patients, linguistic perseveration occurred with left-sided amobarbital injection, although they were all found to have left hemispheric speech dominance according to language testing during the amobarbital procedure. It is argued that these perseverations are best explained as a right hemispheric continuation of a speech motor program previously initiated by the left hemisphere. PMID- 1499308 TI - Proper name anomia. AB - Following a left thalamic infarct, a patient showed a marked impairment in retrieving person proper names in response to faces and to verbal description, despite being able to provide precise information about the persons he could not name and to point to their photograph when the name was provided by the examiner. The patient was also impaired in generating proper names, but could easily retrieve common names as well as geographical names and names of monuments. It is hypothesized that the arbitrary nature of the link between proper names and their referents makes access of phonological forms from the semantic store particularly labile. In agreement with this interpretation is the patient's inability to recall telephone numbers and to learn semantically arbitrary paired associates. PMID- 1499309 TI - Verbal fluency and positron emission tomographic mapping of regional cerebral glucose metabolism. AB - Impairment in verbal fluency (VF) has been a consistently reported clinical feature of focal cerebral deficits in frontal and temporal regions. More recent behavioral activation studies with healthy control subjects using positron emission tomography (PET), however, have noted a negative correlation between performance on verbal fluency tasks and regional cortical activity. To see if this negative relationship extends to steady-state non-activation PET measures, thirty-three healthy adults were given a VF task within a day of their 18F-2 fluoro-2-deoxy-D-glucose PET scan. VF was found to correlate positively with left temporal cortical region metabolic activity but to correlate negatively with right and left frontal activity. VF was not correlated significantly with right temporal cortical metabolic activity. Some previous studies with normals using behavioral activation paradigms and PET have reported negative correlations between metabolic activity and cognitive performance similar to that reported here. An explanation for the disparate relationships that were observed between frontal and temporal brain areas and VF might be found in the mediation of different task demands by these separate locations, i.e., task planning and/or initiation by frontal regions and verbal memory by the left temporal area. PMID- 1499310 TI - Failure of metacontrol: breakdown in behavioural unity after lesion of the corpus callosum and inferomedial frontal lobes. AB - A right-handed man suffered aneurysmal haemorrhage with lesions of the genu and body of the corpus callosum and the inferomedial frontal lobes bilaterally (right more than left). He exhibited remarkable breakdown in behavioural unity characterized by conflict between the two sides of the body, actions inconsistent with verbalizations, and internal conflict over control of the left hand. A major feature of the deficit was its temporal variability. This is interpreted as reflecting intermittent failure of metacontrol processes, which are neural mechanisms for maintaining behavioural unity. Medial frontal structures and their interconnections through the corpus callosum appear particularly important in the maintenance of metacontrol. PMID- 1499311 TI - Impaired visual perceptual categorization in right brain-damaged patients: failure to replicate. AB - The association of both Perceptual Categorization (PC) and Semantic Categorization (SC) with sensory performance was investigated. 28 RBD, 27 LBD and 21 non-brain-damaged subjects were tested with the PC and SC tasks described by Warrington and Taylor (1978) and with 6 sensory tasks. PC was related to sensory performance in RBD but not in LBD patients. SC was only marginally associated with sensory ability in both lesion groups. RBD and LBD patients differed significantly at neither PC nor at SC. Thus the dissociation between PC and SC, described by Warrington and Taylor (1978) was not replicated. Moreover, PC and SC were significantly correlated in both RBD and LBD patients. This suggests that the serial organization of PC and SC is questionable. It is concluded that the associations we obtained between SC, PC and sensory performance are likely to be functional. The contribution of a cognitive factor ("abstraction") to PC and SC is discussed. PMID- 1499312 TI - Variations in lateralized processing among right-handers: effects on patterns of cognitive performance. AB - Two experiments investigated whether individual differences among right-handers in patterns of lateralized processing were related to level of performance on a variety of cognitive tasks presented under non-tachistoscopic conditions. Subjects were divided into two groups of individuals, those who characteristically have greater than average right-hemisphere involvement in functioning and those who characteristically have greater than average left hemisphere involvement. In the first experiment we examined whether characteristic individual differences in hemispheric involvement could predict performance on a facial memory task. The group with relatively greater right hemisphere involvement had better recognition memory than the group with relatively greater left-hemisphere involvement. In the second experiment, we examined whether individual differences in hemispheric involvement could predict performance on a larger set of cognitive tasks. The groups were administered two tasks selected to evaluate left-hemisphere function and two selected to evaluate right-hemisphere function. The results indicated that the groups differed in their profile of cognitive performance. Individuals with greater than average right-hemisphere involvement in processing tended to perform better on tasks indexing right-hemisphere function than on tasks indexing left-hemisphere function, whereas the opposite was true of individuals with greater than average left-hemisphere involvement. Collectively, the results of these two experiments indicate that individual differences in lateralized performance have important implications for individual differences in patterns of cognitive ability. PMID- 1499313 TI - Flash and pattern reversal visual evoked responses in normal and demented elderly. AB - P1 and P2 components of visual evoked responses (VERs) to flash stimuli were compared between patients diagnosed as suffering from Senile Dementia of the Alzheimer Type (AD) and elderly controls. Additionally the P100 component of the VER to pattern reversal stimuli at high and low contrast and using large and small check patterns was compared. Significant differences between moderate AD patients and the normal elderly were found for the P2 component of the flash stimulus and for the P100 component of the high spatial frequency pattern reversal stimuli at low contrast. These findings suggest a deficit in primary visual processing and a selective deficit in secondary visual processing in moderate cases of dementia. This indicates that visual processing capacities of AD patients decline as the disease progresses in line with the continual degeneration of neuronal populations involved with vision. PMID- 1499314 TI - Pure word deafness due to left hemisphere damage. AB - We report the case of a 55 year-old right-handed man who presented with a long lasting pure word deafness following left thalamic bleeding. There was no sign of aphasia. The auditory deficit was specific for language, while recognition of music and environmental sounds was normal. CT, MRI and PET examinations showed that the lesion was anatomically and functionally confined to the left cerebral hemisphere, mainly the white matter of the temporal and parietal lobes. Wernicke's area was largely preserved. It is proposed that pure word deafness was consequent to the isolation of Wernicke's area from incoming auditory information due to the interruption both of the association fibers from the right auditory area traveling across the corpus callosum and of the left auditory radiations. PMID- 1499315 TI - Improvement of renal preservation by adding lidoflazine to University of Wisconsin solution. An experimental study in the rat. AB - The purpose of this study was to investigate the possibility of improving the organ preservation properties of the University of Wisconsin (UW) solution by adding the calcium entry blocker lidoflazine. We also investigated the possibility of decreasing the cold ischemia and reperfusion damage by pretreatment with lidoflazine of the donor and/or recipient. The protective effects of lidoflazine treatment were estimated by measuring the amount of trapped erythrocytes in the rat renal medulla after 48 h of cold storage, subsequent transplantation, and 20 min of reperfusion. Lidoflazine (20 mg/liter) added to the UW solution decreased the amount of erythrocyte trapping from 14.8 +/- 3.1% in controls to 8.6 +/- 1.7% (P less than 0.01). The flow rate of the flush-out solution during the harvesting procedure was also significantly (P less than 0.01) increased when lidoflazine was included in the UW solution (1.10 +/- 0.21 ml/min vs 0.75 +/- 0.22 ml/min). Administration of lidoflazine (0.28 mg/kg body wt) to the donor and/or the recipient did not further reduce the postischemia/reperfusion damage as estimated by the degree of erythrocyte trapping. In conclusion, the results indicate that the preservation properties of the UW solution can be significantly improved by adding lidoflazine to the solution. PMID- 1499316 TI - Microvascular changes of the liver preserved in UW solution. Pathological and immunohistochemical examination. AB - Rat livers preserved in University of Wisconsin (UW) solution for 24 h were compared with those preserved in Euro-Collins (EC) solution before and after liver transplantation using an immunohistochemical method. Tissue ATP and total tissue adenine nucleotide (TAN) were measured using HPLC. The levels of TAN in the UW group or the EC group were significantly low compared with the control group (no preservation) after 24-h storage. In the EC group, the levels of tissue adenine nucleotides (TAN) decreased 1 h after reperfusion and never reached control levels. In the UW group, the levels of TAN increased a little 1 h after reperfusion and increased more 3 h after reperfusion. After 24-h preservation, the expression of factor VIII-related antigen (FRA) in endothelial cells of central veins was weak in the EC group; in the UW group, FRA was clearly detected in these cells. After reperfusion, although severe endothelial cell damage to the central veins and numerous FRA-positive substances were observed in EC group, endothelial cells of central veins retained their normal structure and FRA positive substances were rarely noted in the UW group. In both groups, no endothelial changes were detected in portal veins. From these results, it is concluded that UW solution prevents endothelial cell damage and microcirculatory injury in zone III during the preservation period resulting in prevention of initial graft nonfunction. Also, measurement of the TAN level after reperfusion is useful to predict the function of the graft. PMID- 1499317 TI - Permeability of lipid membranes revised in relation to freeze-thaw processes. AB - Water and solute activity gradients created during freeze-thaw processes produce water and solute fluxes across the cell membrane resulting in volume changes. Under these conditions, osmotic and thermal stresses affect the curvature, the phase behavior, and the surface properties of the lipid bilayer. These structural changes are not considered by the classical formalisms describing permeability of lipid membranes to water and nonelectrolytes such as the Nernst-Planck equation, Eyring's absolute rate theory, and Kedem-Katchalsky's thermodynamic of irreversible processes approach. In this paper, the influence of such changes on the glycerol permeation kinetics are reported. The results indicate that osmotic and chemical effects of the cryoprotectant on the membrane properties affect the rate of volume swelling depending on whether the membrane is in the gel or in the liquid crystalline state. PMID- 1499318 TI - Cryoprotective effect of polyols on rat embryos during two-step freezing. AB - The cryoprotective effect of polyols on rat embryos was measured after two-step freezing, and the mechanism of action of polyols on embryo survival was examined. Rat embryos frozen in solution of polyol by two-step method at the morula stage showed higher survival than that obtained using DMSO. As the number of hydroxyl groups increased, the cryoprotective effect of the polyol increased. However, this was true only when the additive could permeate the cell membrane. Of the additives tested, four or five carbon polyols were most effective at concentrations of 0.3 or 1.0 M than two, three, six, or seven carbon polyols. The highest survival rate was obtained with adonitol, which yielded 83% embryo survival at 1.0 M and 67% even at 0.3 M. Embryos frozen in 0.3 M adonitol and transferred directly into foster mothers without any dilution of the additive after thawing developed into live young. During slow cooling below -40 degrees C, embryonic blastomeres exhibited cell fusion only in the presence of adonitol. These findings suggest that one cryoprotective action of polyols is that the hydroxyl groups act both on the cell surface and the cytoplasm to stabilize the bound water on the embryonic membrane, and that the length of the C-chain determines the permeability of the membrane to the additive. PMID- 1499319 TI - Effect of phosphoenolpyruvate on metabolic and morphological recovery of red cells after prolonged liquid storage and subsequent freezing in glycerol medium. AB - The present study was designed to determine the effects of (i) phosphoenolpyruvate (PEP) treatment of red blood cells (RBCs) previously cold stored for a prolonged period in a liquid medium and (ii) the freezing of these treated cells in glycerol. RBCs stored for 21 days at 4 degrees C were incubated for 30 min at 37 degrees C with rejuvenant solution containing 50 mM PEP, 60 mM mannitol, 30 mM sodium chloride, 25 mM glucose, and 1 mM adenine, pH 6.0, and then frozen at -80 degrees C for 4 weeks. Red cell recovery as frozen and thawed red cells (FTRCs) after deglycerolization was increased to 80 +/- 4% compared to 43 +/- 9% in units without rejuvenation; the percentage of PEP-treated FTRCs was similar to the percentage of FTRCs recovered from fresh RBCs within 5 days after donation. Incubation of RBCs with PEP solution restored ATP and 2,3-DPG to levels seen in fresh RBCs, and also facilitated transformation of crenated RBCs to discocytes. These results indicate that maximum recovery of viable RBCs can be attained when FTRCs are processed from cells stored in the frozen state after they had been rejuvenated with PEP even after prolonged liquid storage. PMID- 1499320 TI - Cryoprotection of red blood cells by a 2,3-butanediol containing mainly the levo and dextro isomers. AB - A 2,3-butanediol containing 96.7% (w/w) racemic mixture of the levo and dextro isomers and only 3.1% (w/w) of the meso isomer (called 2,3-butanediol 97% dl) has been used for the cryoprotection of red blood cells. The erythrocytes were cooled to -196 degrees C at rates between 2 and 3500 degrees C/min, followed by slow or rapid warming. Up to 20% (w/w) of this polyalcohol, only the classical peak of survival is observed, as with up to 20% (w/w) 1,2-propanediol or 1,3-butanediol. Twenty percent 2,3-butanediol 97% dl can protect red blood cells very efficiently. The maximum survival, of 90%, as with 20% glycerol, is a little lower than with 20% 1,2-propanediol and higher than with 20% 1,3-butanediol. Fifteen percent 2,3-butanediol protects fewer red blood cells than 15% glycerol or 1,2-propanediol, with a maximum survival of about 80%. The best cryoprotection by 30% 2,3-butanediol 97% dl is obtained at the slowest cooling and warming rates, where survival approaches 90%. After a minimum, an increase of survival is observed at the fastest cooling rates, which would correspond to complete vitrification. These rates are lower than with 30%, 1,2-propanediol or 1,3 butanediol, in agreement with the higher glass-forming tendency of 2,3-butanediol 97% dl solutions. In agreement with the remarkable physical properties of its aqueous solutions, the present experiments also suggest that 2,3-butanediol containing mainly the levo and dextro isomers could be a very useful cryoprotectant for organ cryopreservation. However, it would perhaps be better to use it in combination with other cryoprotectants, since it is a little more toxic than glycerol or 1,2-propanediol at high concentrations. PMID- 1499321 TI - Performance of a kinetic model for intracellular ice formation based on the extent of supercooling. AB - Cryomicroscopy was used to study the incidence of intracellular ice formation (IIF) in protoplasts isolated from rye (Secale cereale) leaves during subfreezing isothermal periods and in in vitro mature bovine oocytes during cooling at constant rates. IIF in protoplasts occurred at random times during isothermal periods, and the kinetics of IIF were faster as isothermal temperature decreased. Mean IIF times decreased from approximately 1700 s at -4.0 degrees C to less than 1 s at -18.5 degrees C. Total incidence of IIF after 200 s increased from 4% at 4.0 degrees C to near 100% at -15.5 degrees C. IIF behavior in protoplasts was qualitatively similar to that for Drosophila melanogaster embryos over the same temperature ranges (Myers et al., Cryobiology 26, 472-484, 1989), but the kinetics of IIF were about five times faster in protoplasts. IIF observations in linear cooling of bovine oocytes indicated a median IIF temperature of -11 degrees C at 16 degrees C/min and total incidences of 97%, 50%, and 19% at 16, 8, and 4 degrees C/min, respectively. A stochastic model of IIF was developed which preserved certain features of an earlier model (Pitt et al. Cryobiology 28, 72 86, 1991), namely Weibull behavior in IIF temperatures during rapid linear cooling, but with a departure from the concept of a supercooling tolerance. Instead, the new model uses the osmotic state of the cell, represented by the extent of supercooling, as the independent variable governing the kinetics of IIF. Two kinetic parameters are needed for the model: a scale factor tau 0 dictating the sensitivity to supercooling, and an exponent rho dictating the strength of time dependency. The model was fit to the data presented in this study as well as those from Myers et al. and Pitt et al. for D. melanogaster embryos with and without cryoprotectant, and from Toner et al. (Cryobiology 28, 55-71, 1991) for mouse oocytes. In protoplasts, D. melanogaster embryos, and mouse oocytes, the parameters were estimated from IIF times in the early stages of isothermal periods, while the osmotic state of the cell was relatively constant. In bovine oocytes, the parameters were estimated from linear cooling data. Without further calibration, the model was used to predict total IIF incidence under different cooling regimes. For protoplasts, D. melanogaster embryos, and bovine oocytes, the model's predictions were quite accurate compared to the actual data. In mouse oocytes, adjustment of the hydraulic permeability coefficient (Lp) at 0 degree C was required to yield realistic behavior.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1499322 TI - Biochemical modification of plasma ice nucleating activity in a freeze-tolerant frog. AB - Recently, we reported the presence of ice nucleating activity, apparently proteinaceous, in the plasma of a freeze-tolerant frog, Rana sylvatica, collected in autumn and spring. Although this protein has not been purified, its ice nucleating behavior can act as an internal reference for tests that attempt to modify its ability to nucleate ice formation. If the addition of a chemical reagent alters the temperature of ice crystallization compared with the control, it can be assumed that protein modification may have occurred. The ice nucleating protein in R. sylvatica showed resistance to proteolysis with four different proteases although there was a significant reduction in the temperatures of nucleation with these treatments (ANOVA P less than 0.001). However, ice nucleating activity was lost when plasma was treated with the addition of urea or N-bromosuccinimide. Modification of protein sulphydryl groups with iodoacetamide did not affect the crystallization temperature (Tc) but treatment with iodoacetic acid resulted in a significant increase in Tc of plasma. An abrupt loss of ice nucleating ability was observed in plasma samples after heating above 87 degrees C. Anomalous potentiation of ice nucleating activity occurred when the plasma was heated to and held at temperatures between 67-75 degrees C. PMID- 1499323 TI - Cryoprotective effects of yeast extracellular polysaccharides and glycoproteins. AB - Eighteen yeast strains were tested for their ability to survive the freeze-thaw process while being cryoprotected. Cryoprotection was accomplished by combining penetrating and nonpenetrating cryoagents. Four nonpenetrating (two extracellular polysaccharides of yeast and two extracellular glycoproteins of yeast) and two penetrating agents were used together with the nutritive-rich medium. Eight different mixtures were tested. The highest survival rate was obtained with glycoproteins of Rhodosporidium toruloides together with DMSO and nutritive-rich medium. PMID- 1499324 TI - A comparison of the heart rate at different ambient temperatures during long-term hibernation in the garden dormouse, Eliomys quercinus L. AB - Heart rate in hibernating garden dormice, Eliomys quercinus, was studied by means of permanently implanted electrodes; ambient temperatures (TA's) were maintained at 0, 4, 6.5, and 9 degrees C during the 6-month test period in each winter study. The animals were kept under constant conditions in darkness and without food or water. Heart rate remained at a low level during deep hibernation at all TA's studied. There were no differences in midwinter values between the TA's of 6.5 and 9 degrees C: the means were 9-12 beats/min during apnea. Heart rate thus differs from other hibernation parameters studied simultaneously, which were strongly TA dependent. However, the optimal TA of 4 degrees C could be distinguished and heart rate was significantly lower, 8-10 beats/min. At 0 degree C the values were slightly higher: 12-13 beats/min. The TA of 0 degree C was exceptional for all parameters studied. At the beginning of the hibernation season was a transition period with elevated heart rate values. Respiratory related heart-rate changes appeared during periodic respiration, heart rate being significantly higher during respiratory periods at all TA's. At 0, 6.5, and 9 degrees C tachycardia occurred also during apnea, very close to the respiratory period. There are responses that are comparable to hypoxic environmental conditions during hibernation, diving, and pregnancy and under high-altitude conditions. Parallel adaptations appear in heart rate and respiration, i.e., bradycardia and periodic respiration. In conclusion, heart-rate values were low during deep hibernation, and compared with other parameters measured at different TA's heart rate is maintained inside narrow limits during deep hibernation. PMID- 1499325 TI - Enhancement of cellular immune function during cold adaptation of BALB/c inbred mice. AB - The cell-mediated immune function of cold-adapted BALB/c inbred mice was studied in experiments of splenic lymphocyte blastogenesis, indicated by tritium-labeled deoxythymidine incorporation and SDS-PAGE autoradiography of synthetic proteins in lymphocytes. Male BALB/c inbred mice were randomly divided into two groups: control (living at 25 degrees C) and cold-exposed (living at 2 degrees C). Results are as follows: in contrast with the control group, there was an obvious fluctuation of cell-mediated immune function in the cold-exposed group at initial cold exposure because of transient stress to cold; then cell-mediated immune function gradually recovered to control level. From Day 15, the cell-mediated immune function of the cold-exposed group was remarkably enhanced. On Day 15, the lymphocyte blastogenesis rate was increased by 20.66% (P less than 0.05), which implies the onset of cold adaptation; on Days 21 and 31, the rates increased by 80.15% (P less than 0.05) and 40.36% (P less than 0.05), respectively. Two to six months later, with continuing cold exposure, the murine lymphocyte blastogenesis rate in the cold-exposed group remained higher than that in the control group. The lymphocyte protein synthesis of the cold-exposed group, indicated by tritium labeled leucine incorporation, apparently increased on Day 15 and the stimulated rate was 101.47% (P less than 0.05). SDS-PAGE autoradiography of synthetic proteins in lymphocytes demonstrated that after 2 weeks of cold exposure, protein bands were enriched in both quantity and quality. These results are identical to the results obtained from lymphocyte blastogenesis.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1499326 TI - The effect of supercooling on the developmental capacity of mouse embryos. AB - The effect of supercooled storage (at subzero temperatures without ice formation) on compacted mouse morulae and early blastocysts was studied. The embryos were equilibrated with one of three storage solutions containing 1, 3, or 6% each of methanol and glycerol and cooled to -2, -5, -10, or -15 degrees C and stored for up to 24 h to assess the effect of subzero storage at different temperatures and concentrations of the permeating cryoprotectants on embryo survival. Early blastocysts showed substantially greater survival than morulae and, in general, survival of embryos of either stage increased with the concentration of cryoprotectant, while the proportion of embryos surviving decreased with decreasing storage temperature and with increased duration of storage. PMID- 1499327 TI - Echocardiographic assessment of prosthetic heart valves. PMID- 1499328 TI - Prosthetic heart valve performance: long-term follow-up. PMID- 1499329 TI - The biology and practice of surgical drains. Part 1. PMID- 1499330 TI - From metabolite, to metabolism, to metabolon. To Paul A. Srere on the occasion of his 65th birthday. PMID- 1499331 TI - Association of glycolytic enzymes with the cytoskeleton. AB - The diverse physical associations of the glycolytic enzymes with structural components of the cell suggest that the glycolytic enzymes are not entirely soluble in the cell. The relatively low affinities of the associations are likely responsible for the apparently transient interactions. The binding phenomenon is suggested to regulate metabolism through changes in enzymatic activity and facilitates localized enrichment of the enzymes. PMID- 1499332 TI - Structural aspects of citrate biochemistry. PMID- 1499333 TI - Citrate: its relation to free magnesium ion concentration and cellular energy. PMID- 1499334 TI - Structure and mechanism of citrate synthase. PMID- 1499335 TI - Complexes and complexities of the citric acid cycle in Escherichia coli. PMID- 1499336 TI - Regulatory consequences of organization of citric acid cycle enzymes. PMID- 1499337 TI - Substrate channeling of NADH in mitochondrial redox processes. PMID- 1499338 TI - Cellular infrastructure and metabolic organization. PMID- 1499339 TI - Interactions between mitochondria and cytoplasm in isolated hepatocytes. AB - Results from a wide variety of metabolic studies have provided indirect support for conclusions derived from enzymological approaches that the enzymes of the so called soluble cytoplasm (and the mitochondrial matrix) exist within the cell and function in the form of multienzyme complexes and that metabolite channeling takes place between the enzymes of each complex. Our studies support the possibility that the enzymes of glycolysis in liver are segregated from those of gluconeogenesis. Thus, the segregation and aggregation of Krebs cycle enzymes in the mitochondrial matrix, elucidated by Paul Srere, may be an example of a general pattern of enzyme organization pertaining to all metabolic pathways. PMID- 1499340 TI - Orotidylate decarboxylase of yeast and man. AB - The mechanism for ODCase appears to involve the formation of a zwitterion of OMP and a ylid on decarboxylation. Thiamin pyrophosphate catalyzes various decarboxylation and transfer reactions involving ketone groups because the thiazolium ring with its positively charged N atom can, on the loss of a proton from the adjacent C-2, generate a ylid which adds to carbonyl groups to produce a substrate ylid. The unusual aspect, then, of the ODCase reaction is that the substrate itself becomes the ylid, presumably by gaining a proton from ODCase, which results in a positive charge on the N-1 atom of the pyrimidine ring. It is a zwitterion in the transition state which momentarily becomes a ylid on decarboxylation of OMP which then yields the product, UMP. There is no known cofactor for the ODCase reaction. It will be of interest to discover the groups on the enzyme that aid in formation of the zwitterion and the ylid. Further work on the crystal structure and on the production of altered enzymes (where specific amino acids suspected to be important for the reaction are changed) should reveal more details about this important and novel reaction. PMID- 1499341 TI - Enzyme organization and the direction of metabolic flow: physicochemical considerations. PMID- 1499342 TI - Mechanisms of metabolite transfer between enzymes: diffusional versus direct transfer. PMID- 1499343 TI - "Designer membranes": construction of a cell containing multiple membrane-bound cytochromes P450. PMID- 1499344 TI - How carbohydrates cross the lipid membrane of bacterial cells. PMID- 1499345 TI - Protein-protein interaction in the alpha-complementation system of beta galactosidase. PMID- 1499346 TI - Immunopathology of herpes simplex virus infections. PMID- 1499347 TI - Contemporary approaches to vaccination against herpes simplex virus. PMID- 1499349 TI - Controlling herpes simplex virus infections: is intracellular immunization the way of the future? PMID- 1499348 TI - Pathogenesis of herpes simplex virus infection and animal models for its study. PMID- 1499350 TI - The role of T cell immunity in control of herpes simplex virus. PMID- 1499351 TI - The role of antibody in herpes simplex virus infection in humans. PMID- 1499352 TI - Macrophages and other nonspecific defenses: role in modulating resistance against herpes simplex virus. PMID- 1499353 TI - Swallowing in torticollis before and after rhizotomy. AB - To determine risk factors for dysphagia after ventral rhizotomy, videofluoroscopic barium swallowing examinations were done on 41 spasmodic torticollis patients before and after surgery. Radiologic abnormalities were present in 68.3% of the patients before surgery, but these were only mildly abnormal in the majority. After surgery 95.1% showed radiologic abnormalities which were moderate or severe in one-third of the patients. Swallowing abnormalities correlated significantly with duration of torticollis and subjective complaints of swallowing difficulty both before and after surgery, but not with age, sex, or type of torticollis. The major acute postoperative finding was aggravation of preexisting pharyngeal dysfunction. Follow-up from about half of our original sample showed that gradual improvement occurred from 4 to 24 weeks after surgery by subjective report. We review the innervation of intrinsic and extrinsic pharyngeal musculature, and suggest that C1-3 rhizotomies and selective sectioning of the spinal accessory nerve are responsible for aggravation of pharyngeal swallowing dysfunction in the acute postsurgical period. PMID- 1499354 TI - Oral diseases in HIV-1 infection. AB - HIV-associated oral lesions have been reported since the beginning of the AIDS epidemic, be they fungal, viral, bacterial, neoplastic, or non-specific in origin. The most common lesions are oral candidiasis (OC; noted in several forms) and oral hairy leukoplakia (OHL). OC appears to be directly related to levels of immunosuppression while OHL, a newly described lesion, is associated with the Epstein-Barr virus. Although prevalence data for all types of oral lesions are scarce, this review identifies and describes those reported most often. Lesions associated with HIV may appear on most oral mucosal surfaces and may differ from those seen on other body areas. The role of saliva in reducing the potential for transmission of the HIV virus appears to be significant. Physicians and dentists should cooperate in the management of the HIV patient who has oral disease. PMID- 1499356 TI - "Periventricular white matter changes and oropharyngeal swallowing in normal individuals". PMID- 1499355 TI - Periventricular white matter changes and oropharyngeal swallowing in normal individuals. AB - Cranial magnetic resonance imaging (MRI) has revealed patchy periventricular white matter lesions or "unidentified bright objects" (UBOs) in otherwise neurologically intact individuals. Quantitative videofluoroscopic swallowing evaluations and cranial MRI examinations were studied in 49 neurologically normal volunteers (ages 43 to 79 years). Total swallowing duration (TSD) and its subcomponents of oral transit duration (OTD), stage transition duration (STD), and pharyngeal response duration were measured for liquid and semisolid swallows. MRIs were graded from 0, or no UBOs, to 3, or multiple and confluent lesions. The effect of the presence of UBOs on swallowing durational measures and risk factors was analyzed with age differences accounted for statistically (ANCOVA). TSD and OTD for semisolids were significantly differentiated by MRI score (P less than 0.009 and P less than 0.047, respectively). That is, a demonstrable effect was found for an increased number of UBOs on duration of oropharyngeal swallowing in normal individuals. PMID- 1499357 TI - Novel primitive swallowing reflex: facial receptor distribution and stimulus characteristics. AB - We recently described a primitive swallowing reflex: swallowing as a response to a puff of air administered to the face. To identify the facial afferent distribution of this response, the necessary characteristics of the stimulus, and the role of the infant's antecedent behavior, we studied 13 infants who had demonstrated this reflex. We evaluated nine infants by clinically observing for swallowing in response to a total of 135 stimulus applications. All nine had consistently positive responses to the maxillary-ophthalmic area and to the maxillary-mandibular area. Two had consistent responses to stimulation of the mandibular area alone; these were positive. Six had consistent responses to stimulation of the ophthalmic area alone; these were negative. Four infants, evaluated by manometric documentation of swallowing (a total of 137 stimulus applications) demonstrated 47 of 79 (59%) positive responses to stimuli applied to facial areas including any parts of the lips, but only 7 of 28 (25%) positive responses to stimuli applied to facial areas excluding all parts of the lips (chi square P = 0.002). Light touch to any facial area, including the cornea, failed to produce a swallow in any infant. Crying and sleep were incompatible with the reflex. This newly identified primitive swallow reflex seems to require diffuse stimulation, possibly thermal, to the perioral area of the face in an awake and noncrying infant. PMID- 1499358 TI - Food intake by maneuver; an extreme compensation for impaired swallowing. AB - We report two young patients able to exist on exclusively oral intake despite an absent pharyngeal swallow response. Videofluoroscopic swallowing studies showed that both patients used a sequence of devised maneuvers rather than a coordinated pharyngeal swallow to move the bolus, protect the airway, and open the upper esophageal sphincter during bolus ingestion. We conclude that it is possible for young, highly motivated individuals to maintain oral intake despite ablation of neurologic elements crucial for the normal swallow response. PMID- 1499359 TI - Sounds of swallowing following total laryngectomy. AB - Accelerometer transduced sounds of swallowing in total laryngectomees did not show acoustical differences for liquid vs paste swallows, as are found in normals. Compared with normal swallows, tongue propulsion of the bolus in laryngectomee swallows occurred closer in time to a distinctive spectral change associated with bolus flow into the esophagus. Interpretation stressed the lack of mechanical traction from laryngeal elevation contributing to pharyngoesophageal sphincter opening, and the increased role of tongue propulsion in laryngectomee swallows. PMID- 1499360 TI - Achalasia evolving from segmental aperistalsis. AB - A 17-year-old woman was evaluated for dysphagia. Radiologic study revealed a rigid segment 10 cm long in the midesophagus, which was found to be aperistaltic on manometric evaluation. The rest of the esophagus and the lower esophageal sphincter were manometrically normal. Four years later the patient was seen for evaluation of severe dysphagia and symptoms of esophageal overflow. Characteristic radiologic and manometric findings of classic achalasia were noted. The case is discussed as an atypical form of achalasia evolving from a segmental esophageal aperistalsis. PMID- 1499361 TI - Aspiration after stroke: lesion analysis by brain MRI. AB - Aspiration is a common problem following stroke, resulting in feeding difficulties and aspiration pneumonia. Despite past studies using clinical assessments and computed tomographic (CT) scans of the head, the correlation of stroke location with aspiration remains unclear. Since brain magnetic resonance imaging is more sensitive than CT for many stroke types, we have correlated MRI lesions with aspiration in patients who have sustained a stroke. We selected patients with acute stroke who underwent brain MRI and a swallowing evaluation. Aspiration was present in 21 of 38 patients (55%). Patients with just small vessel infarcts had a significantly lower occurrence of aspiration (3 of 14, 21%) compared to those with both large- and small-vessel infarcts (15 of 20, 75%, p = 0.002). Multivariate analysis of several specific brain areas failed to identify a significant association between stroke location and the occurrence of aspiration. These findings suggest that patients who have experienced stroke should be individually evaluated for swallowing dysfunction regardless of stroke location or size, since even small-vessel strokes can be associated with aspiration in greater than 20% of cases. PMID- 1499362 TI - Risk factor patterns for coronary heart disease in China, Japan and Germany. AB - The risk factor patterns for coronary heart disease in China, Japan and Germany were studied. 6,025 Germans, 7,580 Japanese and 2,047 Chinese aged 30-59 were investigated following the protocol of the Gottingen Risk, Incidence, and Prevalence Study carried out in West Germany in 1982. It is concluded that in China, the risk factor intervention focuses mainly on smoking and hypertension; smoking also remains the most important risk factor in Japan; while in Germany the major targets are obesity and hyperlipidemia. However, about 38% of the participants from West Germany showed 3 or more risk factors accumulated per person. Thus the multifactorial risk factor reduction might be necessary in Germany. PMID- 1499363 TI - Cardiovascular consequences of obesity. AB - Obesity is common in populations that are overnourished and can become a significant public health problem. Obesity predisposes to non-insulin dependent diabetes mellitus, hypertension, dyslipidemia, cholelithiasis, some malignancies and osteoarthritis. These consequences that most directly affect the cardiovascular system are dyslipidemia and hypertension. Nations in which obesity is rare should learn from the experience of the countries where it is prevalent, that prevention of obesity is a public health measure rather than weight reduction. PMID- 1499364 TI - Trials in elderly patients with isolated systolic hypertension. AB - The hypothesis that antihypertensive drugs should be prescribed to elderly patients with isolated systolic hypertension is being addressed in at least 3 trials: the Systolic Hypertension in the Elderly Program (SHEP) in the United States, a trial in China, and the Syst-Eur study in Europe. The SHEP trial has recently reported its final morbidity and mortality results. This article summarizes the protocol of the European study. To be eligible for the Syst-Eur trial, patients must be at least 60 years old and have a systolic blood pressure averaging 160-219 mmHg with a diastolic pressure less than 95 mmHg. Patients must give their informed consent and be free of major cardiovascular and non cardiovascular diseases at entry. The patients are randomized into active treatment or placebo. Active treatment consists of nitrendipine (10-40 mg/d), combined with enalapril (5-20 mg/d) and hydrochlorothiazide (12.5-25 mg/d), as necessary. The control group received matching placebos. The drugs (or matching placebos) are stepwise titrated and combined in order to reduce systolic blood pressure by 20 mmHg at least to a level below 150 mmHg. Morbidity and mortality are monitored to enable an intention-to-treat and per protocol comparison of the outcome in the two treatment groups. PMID- 1499365 TI - HDL and apolipoprotein A1 (apo A1). Their effects on retardation of lipid deposition in aortic intima. AB - The aim of this study is to clarify whether apo A1 displays a similar role as that of HDL in preventing the development of experimental atherosclerosis. Results were obtained from 4 groups of experiments. (1) Result from 4 successive experiments of tree shrews indicated that high serum HDL level is the main factor in preventing the development of experimental atherosclerosis; (2) Results from 4 successive experiments in rabbits showed that both HDL and apo A1 were able to decrease the extent of lipid deposition and atheromatous lesion developed in the aortic intima; (3) Apo A1 also inhibited the number of monocytes/macrophages infiltrated in aortic intima at the initial stage of fatty streak formation; (4) Similar as HDL, apo A1 phospholipid liposomes promoted markedly the clearance ability of smooth muscle cells on intracellular cholesterol. Conclusively, apo A1 is effective in preventing the development of experimental atherosclerosis. Further study, however, is required to detect an ideal combination of apo A1 with other component, e.g., phospholipid. PMID- 1499366 TI - Recombinant tissue-plasminogen activator (rt-PA) in acute myocardial infarction in the Chinese in Hong Kong. AB - Eighty-nine consecutive Chinese patients (69 males, 20 females) with acute myocardial infarction treated by 100 mg recombinant tissue-plasminogen activator (rt-PA) (7 intracoronarily, 82 intravenously) at 3.7 +/- 1.0 hours after onset, and intravenous heparin or dipyridamole therapy started at 3 hours, were studied prospectively. Their mean age was 59.6 +/- 10.6 years. Forty-six patients (51.7%) had anterior and 39 patients (43.8%) had inferior infarcts. Clinical evidence of reperfusion was seen in 63 patients (72.8%), while new complications included hypotension (5.6%), heart failure (6.7%), cardiac arrhythmias (76.4%), hematoma around vascular access sites (23.6%), melena (2.2%) and cerebral infarction (2.2%). Maximal changes in coagulation profiles were seen at 3 hours, including a decrease in fibrinogen (by 64.2%), an increase in FDP by 11.7 times and D-dimers by 4.4 times. Nine patients (10.1%) had recurrence of angina and 6 patients (6.9%) died due to pump failure (5) and reinfarction (1). Angiogram at 14 days confirmed TIMI (2 or 3) patency of infarct related arteries in 62/81 (76.5%) patients, with a mean global ejection fraction of 52.5 +/- 12.4%. Nearly all survivors could maintain class I-II functional status after discharge. The safety and promises of rt-PA for acute myocardial infarction in the Chinese were confirmed. PMID- 1499367 TI - Coronary atherectomy with the transluminal extraction endarterectomy catheter. AB - Percutaneous transluminal coronary atherectomy was attempted in 25 consecutive patients with the transluminal extraction-endarterectomy catheter. Successful revascularization with residual stenosis less than 50% in diameter was achieved in 23 patients (92%). There were 2 cases of major complications: one with distal embolization which subsided after rtPA infusion and the other with occlusion of RCA underwent bypass surgery. One patient who had restenosis 3 months after the procedure, was successfully treated with PTCA. The technical aspects, advantages and limitations of this method were discussed. PMID- 1499368 TI - Quinaprilat increases total body vascular compliance in rats with myocardial infarction. AB - To test whether quinaprilat, a new angiotensin converting enzyme inhibitor, has any venous effect, its immediate effects were measured on mean circulatory filling pressure (MCFP), intravascular volume and total body vascular (i.e., venous) compliance in conscious rats with mild congestive heart failure induced by coronary artery ligation. MCFP was determined by inflating a right atrial balloon to arrest the circulation instantly and temporarily. Total body vascular compliance was derived from total circulatory pressure-volume relationships as determined by series measurements of MCFP with different intravascular volume status. In 8 rats with mean infarct size of 26 +/- 4%, 30-minute infusion of quinaprilat (0.1 mg/kg/min) decreased both mean arterial and central venous pressures by 8 mmHg and 0.7 mmHg, respectively (P less than 0.02); heart rate, MCFP, hematocrit and blood volume remained unchanged. Compared with control vehicle infusion, quinaprilat increased the total body vascular compliance (2.09 +/- 0.12 vs 2.69 +/- 0.23 ml/kg/mmHg; P less than 0.05) and decreased extrapolated unstressed circulating volume (34.96 +/- 1.10 vs 28.53 +/- 2.55 ml/kg; P less than 0.02). These data suggest that quinaprilat produces possible venodilation through immediately improved total body vascular compliance thereby reducing cardiac preload in this rat model of chronic heart failure. PMID- 1499369 TI - Lessons in prevention of ischemic heart disease learned from pathological studies of coronary atherosclerosis. AB - The recent status of the extent and severity of atherosclerosis in Japanese children and young adults and its causative factor are presented. The material and data are collected from 2,856 autopsies, with the age range of 1 month to 39 years. Fibrinogen-fibrin metabolism in the arterial wall has a definite role in atherogenesis. The incidence of myocardial infarction in 539 consecutive autopsy cases over 40 years old at Kyushu University is 12.7%. PMID- 1499370 TI - Etiological role of Alternaria alternata in human esophageal cancer. AB - In this paper, the mutagenicity and carcinogenicity of alternariol monomethyl ether (AME), alternariol (AOH), and their relevance to the etiology of human esophageal cancer were studied. These mycotoxins were produced by Alternaria alternata which was the main contaminating fungi isolated from the grain in Linxian County, an area with high incidence of esophageal cancer. This study demonstrated that: 1. AME and AOH might cause cell mutagenicity and transformation; 2. AME and AOH could combine with the DNA isolated from human fetal esophageal epithelium, activate the oncogens, c-H-ras and c-mys in it, and promote proliferation of human fetal esophageal epithelium in vitro; 3. squamous cell carcinoma of the fetal esophagus could be induced by AOH. According to the results of the studies of AME and AOH mentioned above, we consider that Alternaria alternata plays an important role in the etiology of human esophageal cancer. PMID- 1499371 TI - Prevalence of growth hormone deficiency of children in Beijing. AB - 103,753 (male 51,994, female 51,759) primary and middle school students aged 6-15 years in two districts in Beijing city were surveyed from October 1987 to April 1989. The heights of the students were measured. According to the height standard of northern cities in China, 202 students with heights below the 3rd percentile for age were requested for detailed history, physical examination, screening GH test bone age, T4, SGPT, chest X-ray, routine urine test and sex chromatin (in female). If GH less than 10 micrograms/L, two provocative tests (L-dopa or clonidine and insulin hypoglycaemia test) were done. Then the heights of the short students were observed for 1/2-2 years. GHD was diagnosed in 12 cases based on the GH peak levels less than 10 micrograms/L in two provocative tests, whose growth velocity was slower than that for students of the same age and sex. Of these subjects with GHD, total GHD (GH less than 5 micrograms/L) was present in 7 and partial GHD (GH = 5-9.9 micrograms/L) in 5. The 12 GHD students (male 9, female 3) aged 8.9-15.7 years accounted for 1/8,646 in the total surveyed students. The male and female GHD accounted for 1/5,777 and 1/17,253 in the total males and females respectively. PMID- 1499372 TI - Treatment of severe Mooren's ulcer with cyclosporin A eyedrops. AB - Sixteen patients (21 eyes) with severe, progressive Mooren's ulcer, unresponsive to medical or surgical therapy, were treated with 0.5% cyclosporin A (CsA) eyedrops. Only 18 eyes were included in this study. Fifteen eyes showed marked effects within the first 12 days. Eleven eyes completely healed, on the average, in 1.3 months without side-effects. Follow-up for 24-31 months showed no recurrence. The whole-blood level of CsA determined randomly by high-pressure liquid chromatography in 7 patients was 28.95 micrograms/L on the average. It is concluded that autoimmunological mechanism plays an important part in pathogenesis of Mooren's ulcer, and the efficacy of topical CsA is attributable to its effect of local depression of ocular immunopathological reactions. PMID- 1499373 TI - Nuclear morphometry and its prognostic significance in laryngeal squamous cell carcinomas. AB - The five parameters including nuclear area (NA), nuclear perimeter (NP), nuclear diameter (ND), axis ratio and nuclear roundness were evaluated with MIAS200 Image Analysis System (Sichuan University, Chengdu) in 45 patients with laryngeal primary squamous cell carcinoma, which were confirmed pathologically and operated on from January 1977 to October 1987. The results showed that NA, NP and ND are important prognostic indicators. The survival rate in patients with large nuclei (NA greater than 73 microns2, NP greater than 32.5 microns, ND greater than 12 microns) was significantly lower than that in those with small nuclei (NA less than 73 microns2, NP less than 32.5 microns, ND less than 12 microns) (P less than 0.0025). These findings strongly suggest that patients with laryngeal squamous cell carcinoma with large nuclei should be treated more aggressively. PMID- 1499374 TI - An experimental study of pituitary transplantations in rabbits. AB - Experimental pituitary transplantations were carried out between the New Zealand white and American chinchilla rabbits. These two kinds of experimental rabbits were of different genotypes. The grafts were transplanted underneath the median eminences of the recipients after hypophysectomy. The rabbits with the transplants were treated with cyclosporine (CsA) and prednisone for the first month. Blood samples were taken at regular intervals for the determinations of serum thyroxine, prolactin and luteinizing hormone. The results suggested that neonatal grafts could survive and function almost normally with the aid of CsA and prednisone, but not without them. The results also disclosed that the interrelationship between the pituitary graft and the host's hypothalamus could be established. Pituitary transplantation from adult rabbit donors failed even though the recipients had been treated with CsA and prednisone in our experiment. PMID- 1499375 TI - Purification of beta-lactamases and enzyme kinetic studies on aztreonam. AB - Standard beta-lactamases K1, P99, TEM-1, SHV-1 and beta-lactamase K-CAZ purified using FPLC through ion-exchange chromatography and filtration chromatography, were identified by determination of isoelectric points, molecular weights and substrate profiles. The results showed that the beta-lactamase stability of domestic aztreonam was very similar to that of cefotaxime, ceftazidime and much better than that of cefoperazone. Aztreonam showed a high affinity to chromosomal mediated cephalosporinase P99, its Ki for inhibition of P99 with cephaloridine as substrate was 0.0159 microns. Aztreonam and the three third generation cephalosporins tested were not stable to beta-lactamase K-CAZ, which hydrolysed them in different degrees. PMID- 1499376 TI - Organ transplantation in China: retrospect and prospect. PMID- 1499377 TI - A new design of internal fixation for scoliosis and its preliminary clinical application. AB - A new scoliotone composed of screw, socket, distraction rod, lateral mass and compression rod can produce free movement in three different planes and fix the vertebral column in three-dimensions. The instrument has a strong force of fixation, distraction, compression and anti-rotation and it can be locked in any degree angle. Preliminary clinical application in 10 cases showed that when the spinal curvature (Cobb's angle) was less than 50, the average correction rate of scoliosis was 78.2% and that of the hump was 90%; when Cobb's angle was within 50 100 degrees, the average curve correction was 68.2%, and the hump correction 87.7%; when Cobb's angle was 100 degrees, the average curve correction was 63.3%, and the hump correction 82%. The vertebral column needed no external fixation after the operation. Biomechanical characteristics of the vertebral pedicle, and the technical features are discussed. PMID- 1499378 TI - Vulval stone. PMID- 1499379 TI - Adaptive bone-remodeling analysis. PMID- 1499380 TI - Rotationplasty in segmental resections of the femur. AB - The authors report 26 cases of high-grade malignant tumors of the distal femur (23 osteosarcomas, 3 Ewing's tumors) submitted to rotation-plasty. The five-years actuarial survival rate (in the 23 cases of osteosarcoma) was 69% and there was no incidence of local recurrence. The following complications were observed: wound dehiscence (6 cases), arterial thrombosis (in 2 patients submitted to resection and vascular termino-terminal suturing), paralysis of the sciatic nerve (2 cases), delay in consolidation (2 cases), traumatic fracture of the neo-femur (3 cases). All of the complications were resolved favorably, 5 of these requiring surgical treatment (33%). Satisfactory functional results were obtained in all of the cases, except in one patient who had limitation of the ankle joint subsequent to vascular compartmental syndrome. On the basis of the oncological, functional and biomechanical results reported in this study and in the literature, the authors discuss current indications for rotation-plasty. PMID- 1499381 TI - The Gamma nail, sliding-compression plate. A comparison between the long-term results obtained in two similar series. AB - The authors report the results they obtained in a retrospective comparative study conducted on two systems of osteosynthesis used to treat trochanteric fractures: the sliding-compression screw-plate (CHS), and the Gamma nail. Two series were included in the study, each of which was made up of 50 cases; these were comparable in terms of fracture type, age of the patients, associated pathologies, and minimum follow-ups of 6 months. The parameters compared were: surgical trauma, average amount of time before a standing position could be resumed, resumption of motor activity previous to trauma, mechanical behavior of the instrumentation. The results show that both of the means of synthesis are capable of effectively stabilizing pertrochanteric fractures, avoiding the mechanical complications instead observed when more dated instrumentation, such as the screw-plate or nail-plate, are used, systems which are not characterized by a sliding cervico-cephalic screw. The amount of time before walking is resumed is quicker when the Gamma nail is used. There was no significant difference in terms of resumption of motor activity. Surgical trauma was the same in both series when the instrumentation was applied after reduction of the fracture in closed surgery, while blood loss was greater when fracture reduction required by application of the plate was performed in open surgery. PMID- 1499383 TI - Locked posterior dislocation of the shoulder. AB - What the authors mean by locked dislocation of the shoulder is an inveterate posterior dislocation of the humeral head which remains locked within the glenoid cavity as a result of anatomopathological lesion. Based on an analysis of four cases a diagnostic-therapeutic protocol is proposed in which the clinical and radiographic data obtained allows for a reliable diagnosis and suitable treatment. PMID- 1499382 TI - The external fixator in the treatment of closed diaphyseal fractures of the lower limb during childhood. Indications and limits. AB - The authors successfully used an external fixator in 10 children affected by one of the following pathologies: fracture of the femur with poor consolidation and marked shortening of the limb; fracture in a hypoplastic segment; severe multiple trauma; delay in consolidation of pathologic bone; fracture in bone regeneration. On the basis of the results obtained, it is affirmed that the external fixator is the ideal means of osteosynthesis for use in any of the above-described situations. PMID- 1499384 TI - The prognostic value of serum alkaline phosphatase in osteosarcoma of the limbs. AB - The values for serum alkaline phosphatase were evaluated in 340 patients affected with osteosarcoma of the limbs. The percentage of patients with high values for the enzyme at the onset of disease was significantly higher in the 69 cases who presented with metastases at the time of diagnosis, as compared to the 271 cases in which the neoplasm still appeared to be localized (81% vs 62%: p less than 0.001). In this last group of patients, treated with neoadjuvant chemotherapy, an evident relationship between values for alkaline phosphatase and prognosis was demonstrated. The percentage of patients who developed metastases was in fact 22% in the group with normal serum values for the enzyme at the onset of the disease and 40% for the patients with high values of the same (P less than 0.001). These data confirm the prognostic value for serum alkaline phosphatase in osteosarcoma, which should be taken into consideration when planning chemotherapy and in classifying patients for randomized therapeutic studies. PMID- 1499385 TI - Post-chemonucleolysis computed tomographic findings. AB - The CT findings observed 6 months and 2 years after chemonucleolysis in 50 and 34 patients are reported. Emphasis is placed on the persistence of the hernia image in nearly 70% of the cases, together with an increase in degenerative intradiscal signs and degeneration of the facet joints; however, this did not lead to poor results 2 years after chemonucleolysis. PMID- 1499386 TI - Intraoperative ultrasonography imaging in spinal surgery (technique and indications). AB - Intraoperative ultrasonography was conducted in 20 patients; the technique of intraoperative ultrasonography for use in spinal surgery is described. The authors emphasize that this non-invasive method obtains real time images of considerable diagnostic importance, allowing for a significantly minor use of image intensifier, with a consequent reduction in doses for both the patient and the staff. PMID- 1499387 TI - Pure traumatic dislocation of the elbow. AB - A total of 89 patients with simple traumatic dislocation treated at the Rizzoli Orthopaedic Institute between 1975 and 1986 were reviewed. The authors considered trauma mechanism, treatment, and results. The evaluation showed that elbow dislocation without joint fracture has a favorable prognosis with return to complete functions. Frequently, para-articular calcifications do not negatively affect joint function. Immediate reduction and plaster immobilization for 2 to 3 weeks are required to obtain soft tissue repair, and in order to avoid functional restriction as a result of prolonged immobilization. After removal of plaster active mobilization is sufficient to obtain complete joint function. PMID- 1499388 TI - False aneurysms of the circumflex arteries of the femur as a complication of hip arthroplasty: description of one case. AB - The authors report one case of false aneurysms of the medial and lateral circumflex arteries of the femur in a patient submitted to cementless An.C.A. model hip arthroplasty. Clinical symptoms, characterized by fatigue, painful swelling in the proximal third of the thigh, in the anterolateral region, began three months after surgery. After an emergency arteriography was obtained, the presence of an aneurysm of the medial circumflex artery, and of the lateral circumflex artery one month later, was observed. PMID- 1499389 TI - A case of membranous lipodystrophy with skeletal involvement. AB - It is the purpose of this study to describe the orthopaedic features of Nasu disease or membranous lipodystrophy based on the observation of a rare clinical case of the pathology and on a review of the international literature. The case described is probably the first to have been observed in Italy, and may be added to the 80 cases currently known to exist the world over. The disease affects young adults and involves pathologic fractures, as well as psychological and neurological disorders. It is currently of unknown etiology and its course is progressive until the death of the subject. The radiological aspect shows metaepiphyseal polycystic lesions of the long bones, with a tendency to expand, and involvement of the cortex. Causal treatment of the disease is currently not possible. The authors emphasize that differential diagnosis involving other diseases having a similar anatomopathological picture may be obtained, and they propose several suggestions for orthopaedic treatment based on their own experience. PMID- 1499390 TI - [Surgery of juvenile periodontitis]. AB - The clinical efficiency of surgery for juvenile periodontitis (JP) followed-up for 13.5 (6-21) months was evaluated in this paper. A total of 102 teeth in 43 patients were included in the study, of them, three-wall infrabony pocket was in 74 teeth, two-wall infrabony pocket was in 21 teeth, one-wall infrabony pocket was in 7 teeth. After scaling, root planning and flap procedure, the rate of clinical efficiency was 74.51%, of which, three-wall infrabony pocket was 85.14%, two-wall infrabony pocket was 52.38%, one-wall infrabony pocket was 28.57%. The results show that if teeth with JP were effectively treated in time, better clinical efficiency can be obtained likewise, and if sectional osseous defects were properly treated, osseous restoration still is possible. PMID- 1499391 TI - [Discussion of the effect of occlusal factor on bruxism]. AB - Controversy has been existed on the effect of occlusal factor on bruxism. The purpose of this study is to evaluate the effect of occlusal factor on bruxism by clinical examination and photo-occlusion analysis. The patient group and control group are selected for this study. The results show that (1) the occlusal status in centric occlusion and eccentric articulation of the patient and control group has no significant difference; (2) the occlusal contact strength and distribution in centric occlusion of the patient and control group has no significant difference; (3) occlusal interferences are existed in different extent both in patient group and control group. This expresses that most of the subjects can compensate this kind of occlusal disorder without feeling any discomfort; (4) This can be concluded that occlusal factor is not an major causal factor on bruxism. PMID- 1499393 TI - [Study of dento-maxillo-facial growth and development on anterior deep bite with linguoversion of upper incisors during permanent dentition]. AB - By means of computer-X-ray cephalometric system to study the dento-maxillo-facial growth and development was performed in 65 patients of anterior deep bite with lingoversion of upper incisors. The patients were divided into two groups: (1) 35 cases aged 12-16 years and (2) 30 cases aged 17-26 years. The same number of the subjects with normal occlusion were used as control group. The findings were as follows: 1. Besides the dento-maxillo-facial growth and development was abnormal vertically, the posterior anterior discrepancy of the growth trend is also one of the main problems in this kind of malocclusion. 2. The growth of the alveolar bone was inhibited anteriorly by the upper incisors; 3. The deformed mandible has the growth trend to rotate forward and upward in Counterclock wise direction so that it is wise to treat of early. PMID- 1499392 TI - [Experimental canine maxillofacial arterial embolization with ethylcellulose microspheres]. AB - External carotid artery tree embolization with ethylcellulose microspheres (EMS) was performed in ten mongrel dogs. Angiography, microangiography and pathological observations were carried out after embolization. In conclusion, EMS can permanently embolize the peripheral arterioles and histological changes of maxilla and mandible after embolization of internal maxillary artery are mainly nutrition defective and degeneration, such as microfracture of the bones, bony lacunae empty, disappearance of the intima of Haver's canals and pulpal degeneration. No evidence of whole or focal necrosis of the bones could be found from twelve hours to half a year after embolization. PMID- 1499394 TI - [Central carcinoma of the jaws. A radiography and pathological analysis of 36 cases]. AB - Records of 36 cases of central carcinoma of the jaws were collected, including 25 cases of squamous cell carcinoma; 9 cases of salivary gland carcinoma; one case of undifferentiated carcinoma and one case of basal cell carcinoma. The correlation between roentgenographic appearance and the histopathologic types are: (1) most lesions of osteolytic destruction are primary intraosseous carcinoma of the jaws (14/16); (2) most lesions of multilocular destruction are salivary gland carcinoma (8/11); (3) most lesions of unilocular destruction are malignant change of odontogenic cysts (7/9). Among 25 cases of squamous cell carcinoma, 7 cases are malignant change of typical keratocyst; 3 cases are similar to dentigerous cysts; 7 cases though show diffuse osseous destruction, they partly have characters of keratocyst in light microscope. So, the authors suggest that perhaps more central carcinomas of the jaws are arising from odontogenic keratocysts. PMID- 1499395 TI - [Clinicopathological study of osteosarcoma of the jaw]. AB - Eighty-five cases of osteosarcoma of the jaw were analyzed for clinical and histologic characters. According to the predominant histologic differentiation of the tumor, it was divided into osteoblastic, chondroblastic and fibroblastic type. Chondroblastic osteosarcoma was associated with the worst survival rate. The histologic grade was closely related to the prognosis of tumor. PMID- 1499396 TI - [Immunohistochemical research for T cell subsets infiltrating in squamous cell carcinoma of oral cavity by monoclonal antibody]. AB - Specimens from 25 patients with squamous cell carcinoma of the oral cavity were examined immunohistochemically, using Streptavidin-Biotin-Peroxidase Complex (ABC) with a series of monoclonal antibodies. Subsets of the infiltrating T lymphocytes in cancer tissues were identified and analysed. We found that, T cell infiltration was predominant. The degree of T cell infiltration was correlated well to the differentiation of cancer and a significant difference existed in OKT 3 + count between the better and the poorer differentiated tumors. Comparing with OKT4+, OKT8+ cells were predominant around cancer nest, the ratio is 1:2. Our results suggest that T cell subsets play a key role in immune response to tumor. Variable quantities and ratio of T subset might be associated with immune regulation imbalance, and reflected malignant grade of cancer and prognosis of the patients. PMID- 1499397 TI - [Limulus lysate activity of some organisms resided in oral cavity]. AB - Gram-positive and Gram-negative bacteria resided in oral cavity have been investigated using Limulus Lysate Assay. The study showed that both kinds of organisms have Limulus Lysate Activity (LLA). The data from the present study indicated that various species of Gram-positive and Gram-negative bacteria possess different degrees of LLA. There is no significant difference of LLA between Gram-positive and Gram-negative bacteria. PMID- 1499398 TI - [Early histologic and enzyme-histochemical changes to rapid maxillary expansion in the midpalatal sutures of the rabbits]. PMID- 1499399 TI - [The follow-up report on the application of ulnar artery flap in maxillofacial surgery]. PMID- 1499400 TI - [A study of the occlusal rest inclination with three dimensional finite element method]. PMID- 1499401 TI - [Cell kinetics study of oral lichen planus and chronic discoid lupus erythematosus]. PMID- 1499402 TI - [A study of the relationships among occlusal plane, camper plane and hamular notch incisive papilla plane]. PMID- 1499403 TI - [The analysis of the maxillary complete denture and its underlying supporting tissues with three dimensional finite element method under the vertical occlusal force in centric occlusion]. AB - A 3-dimensional finite element method was employed in this study to investigate the stress and displacement states of the maxillary complete denture and its underlying supporting tissues under the vertical occlusal force in centric occlusion. The calculation results show that the harmful transverse tension stresses within the base are concentrated on the maxillary incisor regions and its palatal area near the polishing surface. Pressure is exerted over most of the area of the jaw bone cortical surface and the compression stress is strongly concentrated over the alveolar ridge. The posterior palatal area of the denture base migrates away from the mucosa membrane and the other parts press the underlying tissues. These results indicate the biomechanical mechanism of the maxillary denture fracture and alveolar ridge resorption. PMID- 1499404 TI - [Diagnosis of velopharyngeal incompetence after primary cleft palate repair]. AB - Fifty four patients who had had primary cleft palate surgery and whose speech remained defective were examined by speech intelligibility test, lateral videofluoroscopy and flexible nasopharyngoscopy. We found that there are obvious individual differences in the velopharyngeal closure pattern of the patients with speech deficiency following primary surgery. The velopharyngeal closure patterns can be grouped into five categories according to the manner of the velum and lateral pharyngeal wall movements. The criteria of the classification and its significance are discussed in this paper. PMID- 1499405 TI - [Arnold-Chiari malformation presenting in adult life]. AB - Eleven patients of Arnold-Chiari malformation (ACM) in adults were reported. Nine of them associated with syringomyelia. The etiology, clinical features, diagnosis, differential diagnosis, the findings of SSEP, MEP, EMG, NCV, and the treatment of ACM in adults were discussed. Our observations lead us to consider that both clinical symptoms and examinations are crucial in the diagnosis. In addition, the delineation of ACM in adults with or without syringomyelia can be somewhat difficult by traditional radiological examinations, but can be readily demonstrated by MRI. PMID- 1499406 TI - [Relationship among hyperglycemia growth hormone (CSF) and insulin in serum of cerebral hemorrhage]. AB - 40 patients of stroke were studied. The results showed that in Cerebral hemorrhage the correlation between ascending Growth hormone (GH) of CSF and insulin of serum was negative, but the positive correlation between ascending GH (CSF) and hyperglycemia. In patients of cerebral thrombosis the results of values above were no correlation. The pathological significance in such cases was discussed. PMID- 1499407 TI - [A study of plasma von Willebrand factor concentration in patients with cerebrovascular disease]. AB - The plasma vWF levels in patients with CVD were determined using ELISA technique with two monoclonal anti-human vWF antibodies. The results showed that the vWF values in the acute stage of CVD increased significantly. They gradually decreased third weeks after the onset of the CVD. The vWF in the chronic stage of CVD remained higher than normal, but lower than that in the acute stage. The plasma vWF values showed practically no difference in either cerebral infarction or hemorrhage. The average plasma vWF level in the patients with TIA was higher than that in the controls but lower than that in the patients with complete stroke. It was found that the plasma vWF correlated with platelet aggregation induced by ADP constantly, but not with other risk factors. It was considered that elevated vWF would rather be regarded in CVD as a relatively independent risk factor. PMID- 1499408 TI - [A descriptive epidemiologic study of cerebrovascular disease (CVD) in the five provinces in northwest China]. AB - In the five provinces of Northwest China. the population studied from random sampling was 693,190. The crude incidence rate of CVD was 88.2/100,000, the crude prevalence rate 195.6/100,000, and the crude mortality rate 74.4/100,000. The epidemic levels of CVD in Ning-Xia and Shan-Xi were the highest, Its epidemic levels in the urban areas were higher than those in the rural areas. The prevalence rate of CVD was highest in October. The epidemiologic study suggested that the epidemic levels of CVD in North west China was moderate only in comparison with similar studies carried out in some other parts of China. PMID- 1499409 TI - [Advances in the therapy of cerebral glioma]. PMID- 1499410 TI - [The endocrine abnormalities of depressive patients]. AB - In the present study, the levels of the baseline cortisol, thyrotropin (TSH), triiodothyronine (T3), thyroxine (T4) and growth hormone (GH) were determined in 64 depressive patients, 17 patients with other depressive disorders and 19 normal controls. Meanwhile, dexamethasone suppression test (DST) and insulin tolerance test (ITT) were conducted. The baseline cortisol level at 23:00 in the depressive group (8.12 +/- 5.55 micrograms/dl) was significantly higher than that in the normal control group (4.80 +/- 2.10 micrograms/dl), and DST nonsuppression ratio in the depressive group (14.5%) was significantly higher than those in the other two groups (0%). There were not significantly differences in the levels of the baseline TSH, T3 and T4 between the three groups. There were not significantly differences in the baseline GH level between the three groups, but GH level in the depressive group at 90 min. after infusing insulin was significantly lower than that in the normal control group. The results showed the HPA axis hyperactivity, normal thyroid function and blunted GH response to insulin-induced hypoglycemia at 90 min. in ITT in the depressive patients. PMID- 1499411 TI - [Plasma norepinephrine concentration and 24 hour urinary 3-methoxy-4 hydroxyphenylglycol sulfate excretion in endogenous depressed patients]. AB - The plasma NE concentration was assayed with HPLC-ED and 24 hour urinary MHPG-SO4 excretion was determined in 23 endogenous depressed patients and 17 normal controls. In normal controls, plasma NE concentration was significantly correlated with age and was significantly higher in female than that in male. Plasma NE level in endogenous depressed patients was statistically higher than that in the age- and sex-matched controls (paired t test, P less than 0.05). The causes of the result difference among the past plasma NE studies was discussed and the necessity to design the age- and sex-matched controls in the future plasma NE study was suggested. PMID- 1499412 TI - [Clinical practice of the diagnostic criteria of schizophrenia of Chinese classification of mental diseases II (CCMD-2) in 1,394 inpatients]. AB - Re-diagnosed according to diagnostic criteria of schizophrenia of CCMD-2 was applied to 1,394 inpatients, who were diagnosed as schizophrenia when stayed the hospital in 1990. As a result, 98.5% of the cases conformed with four items diagnostic criteria of schizophrenia of CCMD-2; 98.7% of the cases conformed with the criteria of symptomatology; 99.4% of the cases conformed with the criteria for the course of illness; 99.8% of the cases conformed with the for the degree of seriousness; 100% of the cases conformed with the criteria of exclusion. Concordant rate in subtype: catatonic type 96.7%, hebephrenic type 92.2%, regressive type 90.9%, paranoid type 90.6%, residual type 50%, atypical type 50%. The must common symptoms were affective disorder (91%), disturbance of association (83.5%), delusion (62.2%). Frequency of other individual symptom were obviously difference, from 76.8% to 2.9%. We consider that diagnostic criteria of the schizophrenia of CCMD-2 is a appropriate for application in both clinical diagnosis and research work. PMID- 1499413 TI - [Iatrogenic addiction of pethidine: clinical feature and experience of detoxification]. AB - Narcotic analgesic pethidine is widely applied in clinical practice to relieve pain caused by cancer or severe surgical conditions. Iatrogenic addiction following long term medication of narcotic analgesics have been noticed but rarely documented. In this presentation, the authors studied the clinical feature of pethidine dependency as well as experiences of residential detoxification in analysing 34 cases collected in the National Drug Dependence Treatment Center in previous two years. Manifestation of pethidine addiction are much alike to heroin and all abstinent syndromes can be relieved either by methadone or clonidine within 3 weeks except psychological craving throughout the detoxification period. In conclusion, the authors hold that iatrogenic narcotic addiction of this kind is curable as long as the addicts are highly and conscientiously motivated together with rehabilitation measures after detoxification. PMID- 1499414 TI - [Epilepsy and hypohaptoglobinemia]. AB - The serum haptoglobin (Hp) of 24 patients with familial epilepsy and 21 relatives of them, as well as 21 patients with secondary epilepsy was determined by the method of linear concentration gradient (4-22%) polyacrylamide gel electrophoresis. The mean value of their serum Hp was significantly reduced to 54.83% (P less than 0.001), 76.48% (P less than 0.01) and 74.91% (P less than 0.01) of that of the control (109.63 mgHb/dl, n = 201) respectively. The possible pathophysiological mechanism of the epileptic seizures and reduced serum Hp level was discussed briefly. PMID- 1499415 TI - [A neuropsychologic study in migraine patients]. AB - A neuropsychologic test battery (nine kinds, eighteen items) was administered to 16 patients with classic migraine and 32 with common migraine in between attacks, 20 patients with functional headache and 20 physically and mentally healthy volunteers were sustained the test battery as control. The results suggested that the patients of both migraine groups had higher nervous dysfunction in motor, perception, memory, abstract thought, attention and information processing, statistic analysis showed significant difference between both migraine groups and normal control group. The higher nervous dysfunction became worse with the prolongation of course of migraine. PMID- 1499416 TI - [Transcranial magnetic motor evoked potentials (MEP) and somatic sensory evoked potentials (SEP) in the management of cervical spondylitic myelopathy (CSM)]. AB - Fourteen CSM patients with clinical findings of myelopathy had their diagnoses proved with MRI imaging and at operation. There were a control group of 28 normal subjects for MEP and another control group of 32 for SEP. The results of the study showed that 72.7% had MEP abnormality with prolongation of the central motor conduction time (CMCT) in 7 cases and absence of motor action potentials after C7 stimulation in one of the 11 patients. In 2 patients with prolongation of CMCT, normal SEPs were found in the same arm while 1 patient showed directly a reversal of the results. The short-term follow-up study in 10 patients showed normalization of the prolonged CMCT in one and reappearance of motor action potentials with C7 stimulation in another. The authors considered that the non invasive and painless, transcranial magnetic stimulation of the motor pathways might be useful in the assessment and management of CSM patients and better than the electrical stimulation. PMID- 1499417 TI - [Diagnosis of anterior cruciate ligament injury of the knee joint]. AB - From January, 1979 to May, 1989, 107 patients with problems related to anterior cruciate ligament (ACL) were treated in our hospital. 100 of the patients had anterior cruciate ligament injury confirmed by arthrotomy or arthroscopy. The remaining 7 patients were found to be normal either by arthroscopy or arthrotomy. 29 patients had fresh ACL injury and 71 old. All the patients had history of trauma of the knee joint. Swelling and pain in the affected knee joint took place in fresh cases and few of them complained of instability or deformity of the knee. On examination, floating patella test was positive in the majority of the fresh cases. It was shown that accurate diagnosis could be made by Lachman test rather than by conventional anterior drawer test in dealing with fresh injury, but with old ones, Lachman test didn't show the advantages. Examination under anesthesia or arthroscopy helped a lot in diagnosing fresh ACL injury. Anterior drawer test (ADT) was significant in determining the existence of ACL injury. When ADT was positive, ACL injury was found in the majority of the cases, however, injured ACL couldn't be ruled out by negative ADT only. Positive valgus stress test on 0 degrees position suggests possibility of ACL injury, even ADT was negative. Despite the negative anterior drawer test positive posterior drawer test on three directions indicated the injury of the posterior cruciate ligament and the anterior cruciate ligament. The positive rate of ADT was higher than that of pivot shift test in dealing with anterior cruciate ligament injury. Positive pivot shift test suggests ACL injury. PMID- 1499418 TI - [Interposition arthroplasty with pedicled island fascia flap. Experimental study and clinical application]. AB - Interposition arthroplasty of knee joint, using island fascia flap, was performed on 90 rabbits. The fascia flap was vessel pedicled in 54 rabbits and not vessel pedicled in 36 for control. Results of the vessel pedicled island fascia flaps showed that clinically, the range of joint motion was 142.5 degrees on the average. Histologically, the transplanted fascia showed good vascularity and elasticity. There were no signs of adhesion or degeneration. Analogous cartilage appeared in 12 to 15 months. In the control group, the average joint motion was 83.61 degrees and the transplanted fascia showed degeneration of varying degree in each cases. On the basis of these experimental findings, we performed interposition arthroplasty with vessel-pedicled island fascia flap on 20 patients suffering from different joint diseases. The joints were 14 hips, 3 knees, and 3 elbows. Follow-up for 9 to 48 months after arthroplasty revealed clear-up of previous troubles with satisfactory function. PMID- 1499419 TI - [Relation of ultrastructural changes of articular cartilage and the arthroscopic classification in osteoarthritic knee]. AB - This paper reported the ultrastructural changes found in the diseased articular cartilages of 43 osteoarthritic knee joints, which were assessed according to the "Arthroscopic classification of the articular cartilage". The electron microscopic findings and the arthroscopic classification of the articular lesions were correlated. The lesioned articular cartilage revealed two categories of pathological changes. 1. The changes on the part of the articular chondrocytes comprised (1) The nucleus showed pyknosis and karyorrhexis. (2) The cytoplasm exhibited fat droplets, glycogen granules, and/or microfilaments. Lysosomes also emerged frequently. The mitochondria swelled and the rough-surfaced endoplasmic reticulum dilated and became vesiculated. At the same time there was detachment of cell processes or of the cytoplasmic membrane. The chondrocyte underwent necrosis, contracted and eventually disintegrated into lipid debris. These changes increased in extent and degree with the lesion and the severity went parallel with the sequence of the "Arthroscopic stage classification". 2. The changes on the part of the matrix included appearance of electron-dense lipid debris and numerous, coarse and banded collagen fibrils. They resided both in the pericellular matrix and in the general matrix. Sometimes fibroblast-like cells made their appearance in the matrix. These cells also revealed degenerative changes. All these changes went parallel with the sequence of the "Arthroscopic grade classification". PMID- 1499421 TI - [Current status in anterior cruciate ligament repair with artificial ligament]. PMID- 1499420 TI - [Allotransplantation of meniscus in dog's knee. An experimental study]. AB - This experimental study was to show the difference and outcome of allotransplantation and autotransplantation of meniscus in dogs. In the experimental group (9 dogs), the lateral meniscus was removed and replaced by one preserved for 2 weeks in tissue culture. In the control group (9 dogs), the lateral meniscus was excised but was sutured back to the place immediately. The specimens in each group were taken at 3, 6, 12, and 24 weeks after operation, and were examined microangiographically and histologically under light microscope and electron microscope. The results in both groups showed that the meniscus united to the capsule, chondrocytes in the menisci were intact and the collagen fiber orientation was regular. The articular cartilage of the uncovered area of the tibial plateaus showed normal appearance, and vascular neogenesis in the meniscal periphery was found 12 weeks after operation. These observations suggest that allogenic meniscus maintains its original histologic pattern and functional behavior after its transplantation. It makes possible to protect the knee joint from osteoarthritis. PMID- 1499422 TI - [Risk factors of acute pancreatitis]. AB - A total of 689 operative cases of acute necrotic pancreatitis (ANP) were collected from 42 hospitals all over the country by the ANP Cooperative Study Group in the years of 1987 to 1989. General data, laboratory findings, pathology of the pancreas and the type of surgical treatment were analysed according to the outcome of the patient. The results showed that 37% of the cases were related to cholelithiasis, the highest incidence was in age above 60, and female patients were predominant and with higher mortality. Laboratory findings at admission, WBC greater than 20,000/mm3, Hb greater than 15 g%, blood sugar greater than 200 mg%, serum bilirubin greater than 5 mg%, BUN greater than 20 mg%, and serum calcium less than 7 mg% were related to the markedly elevated mortality rate. Operative findings noted in patients with bloody or cloudy peritoneal fluid, necrotic changes up to 75% of the pancreas, more than 2 areas of extrapancreatic involvements and resection of a large portion of the pancreas was found to be necessary were all related to a higher mortality. And emergency operations performed within 24 hours after the onset of the disease was also related with a highest mortality rate. PMID- 1499423 TI - [Diagnosis and treatment of closed complete rupture of patellar tendon. Analysis of 11 cases]. AB - Eleven cases of closed complete rupture of patellar tendon (4 neglected ruptures and 7 fresh ruptures) were treated. Seven of them were treated in extension for 6 8 weeks after operation, 1 was immobilized with patellar traction in the early stage on bed, and 3 were mobilized and assisted with movable brace standing and walking through the body weigh on the knee in the early stage after operation. The aim was to promote the functional recovery of the knee joint. The mechanism of injury, clinical diagnosis, treatment and rehabilitation of closed rupture of patellar tendon were discussed in combination with clinical experience. And the suggestion of movement and active recovery in the early stage after patellar tendon surgery was put forward. PMID- 1499424 TI - [Prognostic significance of cellular DNA ploidy level of the breast cancer]. AB - This paper reports that cellular DNA ploidy level of paraffin-embedded histological material from 47 patients with stage II breast cancer was measured by flow cytometry. Meanwhile, the influence of cellular DNA level on disease-free survival (DFS) of postoperative patients for the breast cancer was analyzed. The results showed eighteen (38.3%) of tumors examined were DNA diploid, and the remainder were DNA aneuploid. Patients with diploid cancer had a significantly better disease-free survival compared with the patients with aneuploid cancer (P less than 0.02). Our results suggested that cellular DNA ploidy level is a good prognostic factor and of important significance in predicting prognosis of patients with the breast cancer. PMID- 1499425 TI - [Low dose heparin in the treatment of deep vein thrombosis]. AB - From 1988 to 1990, 45 cases of lower extremity deep vein thrombosis (DVT) was confirmed by 99mTc radionuclide venography (RNV) at PUMC hospital. Each case was treated by subcutaneous injection of low dose heparin. 21 cases of the 45 cases had post-therapeutic RNV. The results were excellent in 19 cases (complete improvement: swelling, discolouration and pain disappeared), good in 18 cases (marked improvement) and poor in 8 cases (incomplete improvement). Low dose heparin subcutaneous injection can relieve symptoms of DVT and avoid bleeding complication. PMID- 1499426 TI - [Experience in surgical treatment of tetralogy of Fallot]. AB - Corrective Surgery was done in 122 patients with tetralogy of Fallot between May 1981 and Oct. 1989. The surgical mortality was 7.4% (9 patients) and no late death were noted. Multiple stenoses of the RV out-flow tract were observed in 84 patients (69%). The rate of patching of RV out-flow tract was 85.2%. The operation was performed without preoperative cardiac catheterization or angiocardiography in 24 patients (19.6%). Selection of cases without angiocardiography, operative techniques, and management of anomalous coronary vessels were discussed. PMID- 1499427 TI - [Long-term effect of one-stage urethroplasty with perineoscrotal insular skin tube in the treatment of complex posterior urethral stricture]. AB - Thirty-one cases with complex stricture of posterior urethra were treated with one stage urethroplasty adopted perineoscrotal insular skin tube. The results of follow-up for 1 to 6 years were as follows: All cases urinated normally; The cystourethrography in 21 cases showed that urethrae were unobstructed; The urinary flow studies were carried out in 16 cases and the results showed that urinary flow rate curves were normal and that the maximum flow rate, the mean flow rate and the voiding time were all beyond normal values; The urethroscopy in 8 cases revealed that the surfaces of skin tubes remained smooth and without growth of hair stem. The facts stated as above indicated that this procedure was an ideal method for the treatment of long posterior urethral stricture. PMID- 1499428 TI - [Large dose of penicillin misinjected into the spinal subarachnoid space]. AB - Large dose of penicillin was misinjected into the spinal subarachnoid space of 3 patients. Dangerous symptoms such as epileptic status, difficult respiration and severe cerebral edema occurred. Fortunately, the patients were treated promptly without sequelae. PMID- 1499429 TI - [Complications of hump nose after transplantation of tissue ersatz materials. Analysis of 349 cases]. AB - Since 1986, 349 cases of postoperative complications of hump nose were treated (local high lension in 155, shape nonsatisfaction 104, red twelling and distortion 64, transplant exposure 13, and rejection and/or infection 13) and satisfactory results were obtained. The causes of these postoperative complications, remedial methods, and relation of ersatz materials to the complications were analyzed. PMID- 1499430 TI - [Role of neutrophil and hydroxyl radical in shock-induced gut origin infection]. AB - The relative roles of hydroxyl radical and neutrophils in the pathogenesis of shock-induced mucosal injury and gut origin infection (GOI) were determined. The incidence of GOI was higher in the shocked rats (30 mmHg for 30 min) than the sham-shock controls (87% vs 12.5%; P less than 0.01). Administration of the hydroxyl radical scavenger, dimethyl sulfoxide (DMSO) or iron chelator and deferoxamine reduced the incidence of GOI from 87% to 20% and 40% respectively (P less than 0.05). DMSO and deferoxamine appeared to prevent shock-induced GOI by blunting the magnitude of shock-induced mucosal injury. In contrast, neutrophil depletion did not prevent GOI or protect the intestinal mucosal in the shocked rats. Instead, the incidence of systemic spread of bacteria past the mesenteric lymph nodes to the livers and spleens of the shocked rats was higher in the neutrophil depleted rats (56%) than any other group (7%) (P less than 0.01). Thus, shock-induced GOI and intestinal injury appears to be mediated by xanthine oxidase generated oxidants such as hydroxyl radical rather than neutrophil generated factors. In addition, neutrophil depletion may be clinically deleterious, since it promotes systemic sepsis rather than preventing shock induced GOI. PMID- 1499431 TI - [The clinical and experimental research on acute pancreatitis]. PMID- 1499432 TI - [Early arthroscopy in diagnosis and treatment of acute injury of the knee]. AB - Twelve patients with swelling and functional embarrassment of the knee joint caused by a traffic accident were radiographically found to have tibial plateau fractures (7 patients), posterior dislocation (1), fracture of anterior tibial spine (1), single fracture of the posterior tibial spine (1), anterior dislocation (1), and negative findings (1). Arthroscopy was performed 2 to 10 days after trauma, revealed associated injuries not shown on X-ray films in every knee including rupture of cruciate ligaments (ACL 8, PCL 1), tear of menisci (lateral one 8; medial one 2), and disruption of collateral ligaments (medial one 3; lateral 1). These injuries were promptly treated accordingly either through the scope or by open operation. Beside, inadequately reduced bone fragments, viewed through the scope, were further corrected incidentally and conveniently. We believe that early arthroscopy for acute knee injury is a real necessity in perfecting diagnosis and improving treatment. PMID- 1499433 TI - [Clinical analysis of Vogt-Koyanagi-Harada's disease and its association with HLA]. AB - Clinical analysis of 34 patients with Vogt-Koyanagi-Harada's disease in Hunan Province showed that most patients had good visual prognosis following intensive corticosteroid therapy. A multivariate stepwise regression analysis indicated that visual acuity at the first visit, elapse of time before treatment began, duration of papilledema, and presence of ocular complications were significant factors for eventual visual acuity. HLA typing on 25 patients and 65 normal controls suggested that HLA-DR4 and DRW53 might be an immunogenetic background for the high incidence of the disease in oriental populations. PMID- 1499434 TI - [Development of the lens and zonulae in the human embryo]. AB - The embryonic development and ultrastructures of the lens and zonulae in 212 eyes of 131 human embryos were studied by light and electronic microscopy, with the finding that the capsule and zonulae appeared earlier than previously reported. The laminate structure of the capsule was observed in the 7 week embryo, and the early structures of zonulae were discernible in the 10th week on the basement membrane of the non-pigmental epithelium of the ciliary body and on the capsule, indicating that the capsule was specialized basement membrane of the lenticular epithelial cells, and the zonulae originated from the non-pigmental epithelium of the ciliary body and the capsule of lens. PMID- 1499435 TI - [Experimental autoimmune uveitis--a clinical and pathological study]. AB - Experimental autoimmune uveitis (EAU) was induced in 95% of guinea pigs after immunization by a single intradermal injection of homologous retinal tissue in Freund's complete adjuvant and subcutaneous injection of dead pertussis bacilli. The clinical features were circumcorneal injection, cells and flare in the anterior chamber, vasodilation in the iris, and marked cellular exudate in the vitreous. The pathological changes were characterized by diffuse proliferative granulomatous panuveitis, consisting of lymphocytes, macrophages, and epithelioid cells. The outer layers of the retina were disrupted or missing in areas where the pigment epithelium was damaged. PMID- 1499436 TI - [Establishment and computer drawings of a dynamic mathematical eyeball model]. AB - A dynamic mathematic model of the eyeball is established with the computer on the basis of ocular anatomical data and equations of the axial length as the variable in relation to other parameters. With an automatic plotter, the model is transformed into 4 geometric diagrams of the frontal and lateral views, and the meridian and coronary sections. Meanwhile, a set of pictures for intraocular foreign body localization is developed. PMID- 1499437 TI - Immunonutrition and enteral hyperalimentation of critically ill patients. AB - Physicians need to be maximally aggressive in their use of total enteral nutrition (TEN) in the critically ill patient, due to its lower cost, better physiology, and lower complication rate when compared to parenteral therapy. Various components in TEN such as glutamine, arginine, RNA nucleotides, omega-3 fish oils, and fiber, may have important roles in immunonutrition by maintaining gut integrity, stimulating the immune system, and preventing bacterial translocation from the gut. For each patient, the physician must choose the optimal enteral formula for that particular disease or organ failure state to maximize nutrient substrate assimilation and tolerance. Total parenteral nutrition (TPN) should be used only when a true contraindication to enteral feedings exists or as adjunctive therapy when full nutritional requirements cannot be met by TEN alone. PMID- 1499438 TI - Alterations in protein kinase C system of colonic epithelium during fasting refeeding. Evidence for protein kinase C independent pathway of enhanced proliferative activity. AB - In the present study, we compared (1) incorporation of [3H]dThd into DNA, (2) total protein kinase C (PKC) activity, (3) the subcellular distribution of PKC, and (4) PKC isozyme (alpha, beta and gamma) mass in colonic mucosal scrapings and isolated superficial and proliferative colonic epithelial cells from 48-hr fasted, 48-hr fasted-refed, and ad libitum-fed rats. Total colonic mucosal PKC activity and PKC alpha mass were higher and the in vivo rate of [3H]dThd incorporation into mucosal DNA was markedly depressed in 48-hr fasted rats compared to ad libitum-fed or fasted-refed rats. These alterations were localized predominantly to the proliferative pool of colonic epithelial cells. Despite an 11-fold increase in mucosal DNA synthesis, no alterations in total mucosal PKC activity were detected in fasted-refed rats compared to rats fed ad libitum. Moreover, no differences in the subcellular distribution of PKC were noted among any of the dietary groups. Intrarectal instillation of deoxycholate activated PKC and increased DNA synthesis 1.5- to 2-fold. Deoxycholate-induced increases in DNA synthesis, but not those induced by refeeding, were inhibited by treatment of rats with the PKC inhibitors H-7, sphingosine, or staurospaurine. The results do not support a role for PKC in the mediation of increased proliferative activity of colonic mucosa induced by refeeding. PMID- 1499439 TI - Cytokine effects in a human colonic goblet cell line. Cellular damage and its partial prevention by 5 aminosalicylic acid. AB - The aim of the present study was to investigate the effects of cytokines on intestinal goblet cells in vitro. For this purpose, we examined the effects of recombinant interferon gamma (IFN-gamma) and tumor necrosis factor-alpha (TNF alpha) on the human colonic goblet cell line Cl.16E by morphological and kinetic studies, and by the assessment of mucus production during IFN-gamma/TNF-alpha treatment. Control cultures of Cl.16E cells grown on nitrocellulose filters formed monolayers of polarized goblet cells, which had kinetic characteristics similar to those of a differentiated epithelium in steady state. The combined action of IFN-gamma and TNF-alpha caused a dose-related cellular exfoliation, leading to the formation of a mucoid cap made of mucus and cellular debris. The remaining viable cells underlying the mucoid cap were cuboidal and devoid of mucus granules. A dose-related increase in cellular incorporation of [3H]thymidine was reactive to the cytokine-induced cell loss. The synergistic effects of IFN-gamm and TNF-alpha were found to be reversible when the cells were reincubated in a culture medium without cytokines. Furthermore, 5-aminosalicylic acid partially protected Cl.16E cells against cellular injury caused by IFN-gamma and TNF-alpha. On the whole, these morphological and kinetic findings argue that the changes induced in Cl.16E cells by IFN-gamma and TNF-alpha closely parallel those observed during the acute phase of ulcerative colitis, and show that these cytokines can regulate intestinal mucus production by modulating cellular exfoliation, thus leading probably to a reinforced protection of the damaged mucosa. PMID- 1499440 TI - Risk factors for small bowel cancer in Crohn's disease. AB - Suspected risk factors for adenocarcinoma of the small bowel in Crohn's disease include surgically excluded small bowel loops, chronic fistulous disease, and male sex. Review of all seven University of Chicago cases failed to confirm any suspected risk factor. A case-control study was performed to identify possible alternatives. Each case was matched to four randomly selected controls from an inflammatory bowel disease registry matched for year of birth, sex, and confirmed small bowel Crohn's disease. Three factors were significantly associated with the development of cancer: (1) Four cancers developed in the jejunum, and jejunal Crohn's disease was associated with the development of cancer [odds ratio (OR) 8.0, 95% confidence interval (CI) 1.6-39.3]. (2) There was an association between the development of cancer and occupations known to be associated with an increased colorectal cancer risk (OR 20.3, CI 2.7-150.5). Three cases (a chemist with exposure to halogenated aromatic compounds and aliphatic amines, a pipefitter with exposure to asbestos, and a machinist with exposures to cutting oils, solvents, and abrasives) and one of 28 controls (a fireman with multiple hazardous exposures) had an occupational risk factor. (3) Among medications taken for at least six months, only 6-mercaptopurine use was associated with cancer (OR 10.8, CI 1.1-108.7). In conclusion, proximal small bowel disease, 6 mercaptopurine use, and hazardous occupations are associated with cancer of the small bowel in patients with Crohn's disease and can be added to the list of suspected risk factors. PMID- 1499441 TI - Gastroesophageal pH step-up inaccurately locates proximal border of lower esophageal sphincter. AB - Limiting the widespread use of 24-hr pH monitoring is the necessity of manometrically placing the pH probe 5 cm above the proximal lower esophageal sphincter (LES) border. Therefore, we prospectively compared LES localization by gastroesophageal pH step-up with manometry in 71 patients and 14 asymptomatic volunteers. The gastroesophageal pH step-up significantly correlated with the proximal LES border in patients (r = 0.53, P less than 0.0001) and volunteers (r = 0.91, P less than 0.0001). Based on previously published criteria, the pH step up value was considered acceptably accurate if it was within +/- 3 cm (6 cm total span) of the manometrically determined proximal LES border. In 58% of patients and 29% of volunteers the pH step-up occurred outside this accuracy range. Esophagitis (P = 0.015) and abnormal reflux parameters (P = 0.002) were variables contributing to this error. Subsequent analysis found that the pH step-up overestimated the proximal LES border and occurred at the midportion of the sphincter. The pH step-up still inaccurately located the mid LES in 34% of patients. Therefore, manometry should remain the standard for accurate LES localization prior to placing the pH probe. PMID- 1499442 TI - Interaction of gastroesophageal reflux and esophageal motility. Evaluation by ambulatory 24-hour manometry and pH-metry. AB - The present study addresses the question of whether esophageal motility shortly before, during, and after gastroesophageal reflux (GER) is different in patients with GER disease and healthy controls. Twenty-four-hour continuous recordings of intraesophageal pressures and pH were performed in 12 unselected patients with clinically proven GER disease and in 11 volunteers using a new ambulatory and digital recording device. All GER episodes in each studied subject were classified according to their associated motility pattern shortly before (induction period) and during (response period) GER. More GER episodes were analyzed in patients than in volunteers (median: 41 vs 26, P less than 0.05), and a total of 917 GER episodes (593 in patients, 324 in volunteers) was recorded. During the induction period patients more often had irregular esophageal contractions (median: 23% vs 13%, P less than 0.05) and less often had a peristaltic sequence (median: 6% vs 21%) than normals. No difference between patients and controls existed when comparing the frequency of negative pressure peaks or common cavity phenomena shortly before GER. During the response period peristaltic motility in patients was decreased (median: 10% vs 47%, P less than 0.05). We conclude that: (1) GER events in GER patients are more often associated with irregular esophageal contractions than in healthy controls; (2) GER patients present with a diminished, if any, esophageal peristalsis during GER; and (3) combined ambulatory manometry and pH-metry provides clinically useful information on the individual pathogenesis of GER disease, which is superior to the information retrieved by pH-metry alone. PMID- 1499444 TI - Continuous versus intermittent acid exposure in production of esophagitis in feline model. AB - Our morphometric feline model of acid-induced esophageal damage histologically resembles human reflux esophagitis. The histologic scoring system includes intensity and linear extent of basal cell hyperplasia, intraepithelial and subepithelial segmented leukocytes, and ulcers. Each of these four categories is scored from 0 to 4, for a potential total score of 16. Some reports have indicated that the long-duration acid exposure episodes during recumbent nighttime reflux are apt to be associated with greater injury than shorter episodes during daytime upright exposure. We tested the hypothesis that longer single exposures to acid would incite greater morphologic damage in the cat than would multiple, shorter acid exposures. To study the influence of continuous versus intermittent hydrochloric acid exposure, groups of six cats each were infused continuously (single infusion) for 15, 20, or 30 min, and compared with cats infused for 2-min acid infusion times. Our studies indicate that total acid exposure and mucosal damage are more likely to be greater after multiple episodes of the same total duration with adequate clearing (ie, awake upright reflux) than after single long episodes of acid exposure that are poorly cleared (ie, sleeping). PMID- 1499443 TI - Effect of cold stress on postprandial lower esophageal sphincter competence and gastroesophageal reflux in healthy subjects. AB - The effect of cold stress on postprandial lower esophageal sphincter competence and gastroesophageal reflux was investigated in nine healthy subjects. All subjects were studied twice in a randomized order according to a common protocol: 30 min after completion of a 700-kcal meal they put their nondominant hand in water either at 37 degrees C (control stimulus) or at 4 degrees C (stressful stimulus) cyclically for 20 min. Pulse rate and blood pressure rose significantly (P less than 0.01) during the stressful stimulus, but remained unaffected by the control stimulus. Rate of transient lower esophageal sphincter relaxations/30 min [median (interquartile range)] was similar before and during control stimulus, 4 (2.7-5.0) and 3 (2.0-4.5), respectively, whereas it was markedly inhibited during the stressful stimulus [from 5 (3.7-6.0) to 2 (1.0-2.0); P less than 0.05 vs control stimulus]. Rate of reflux episodes/30 min was also similar before and during control stimulus, 1 (0-1.2) and 1 (1.0-2.2), but fell consistently during the stressful stimulus [from 2 (0-3.2) to 1 (0-2.0); P less than 0.05 vs control stimulus]. Percentage of transient lower esophageal sphincter relaxations accompanied by a reflux episode was unaffected by stress as was basal lower esophageal sphincter pressure. It is concluded that cold stress decreases the postprandial rate of transient lower esophageal sphincter relaxations and reflux episodes in healthy humans. PMID- 1499445 TI - Acid perfusion and edrophonium provocation tests in patients with chest pain of undetermined etiology. AB - During the last five years, 672 patients were referred to our esophageal investigation unit; 110 patients (16.3%) of these presented with chest pain of undetermined etiology (CPUE) alone. Since the nature of this pain is intermittent and rarely present during the diagnostic study, acid perfusion and intravenous edrophonium tests were added as provocative tests after baseline esophageal manometry. Following completion of the motility studies, 24-hr pH study was performed to detect gastroesophageal reflux (GER). Twenty-nine patients (26.4%) had positive acid perfusion (APT) test whereas 26 patients (23.6%) had positive edrophonium test (ET). In the group of patients with positive acid perfusion test, 12/29 (41.3%) had GER, 8/29 (27.5%) had both motility disorder and GER, 2/29 (6.8%) had motility disorder, and 7/29 (24.1%) had normal esophageal motility and 24-hr pH studies. In the other group, 13/26 (50%) had motility disorder and 13/26 (50%) had both motility disorder and GER. There were no significant differences between the two tests as far as reproducibility of symptoms was concerned. We conclude that ATP and ET showed the esophageal origin of CPUE in half of our patients and therefore in a substantial percentage of patients the esophageal origin of chest pain will remain very difficult to prove. PMID- 1499446 TI - Effect of indomethacin and misoprostol on fasted gallbladder volume and meal induced gallbladder contractility in humans. AB - Impaired gallbladder contractility is a prerequisite for gallstone formation in animal models. Prostaglandins are important mediators of gallstone formation and may affect gallbladder contractility in animals. The aim of this study was to evaluate the effect of indomethacin, an inhibitor of prostaglandin synthesis, and misoprostol, a synthetic prostaglandin, on gallbladder contractility in man. Seven male volunteers (18-33 years old, mean age 23 years) were studied under blinded conditions after an overnight fast, during control periods and following ingestion of indomethacin 125 mg (75 mg at 10 PM, 50 mg at 6:30 AM) or misoprostol 800 micrograms (400 micrograms at 10 PM, 400 micrograms at 6:30 AM) orally. Gallbladder residual volume was determined by real-time ultrasonography before and 10, 20, 30, 40, and 50 min after ingestion of a standard liquid fatty meal stimulus. Fasting gallbladder volume (milliliters) was similar in all three periods [control 20.8 (1.6); indomethacin 20.8 (2.9); misoprostol 18.3 (1.6)]. The fatty meal stimulus caused prompt contraction, resulting in minimum residual volume of 7.5 (1.4) ml in the control period. Pretreatment with misoprostol or indomethacin did not affect the minimum volume obtained compared with control period [misoprostol: 5.8 (1.4) ml; indomethacin 5.9 (1.3) ml)]. Thus administration of indomethacin and misoprostol had no effect on fasting gallbladder volume or gallbladder contractility in humans as assessed by ultrasonography. PMID- 1499447 TI - Effect of cholecystectomy on gallbladder bile composition. AB - Human bile samples are commonly used in biliary research; however, the optimal sampling technique is not known. The current study examines whether bile obtained prior to operative manipulation of the gallbladder differs in composition from samples obtained after cholecystectomy. Gallbladder bile samples were obtained from 26 patients undergoing cholecystectomy. An initial sample was obtained prior to manipulation or devascularization of the gallbladder, and a second sample was obtained after the removal of the gallbladder from the operative field. Gallbladder bile pH and total protein were significantly increased in the postcholecystectomy samples. Bile obtained after cholecystectomy also contained significantly less phospholipid. Gallbladder bile cholesterol, total bile acids, bilirubin, ionized and total calcium, cholesterol saturation index, and total lipids were similar between techniques. These results indicate that manipulation of the gallbladder during cholecystectomy produces alterations in gallbladder bile composition. These results also emphasize the need for consistent sampling technique when obtaining samples for biliary research. PMID- 1499449 TI - Response to hepatitis B vaccination by liver transplant candidates. AB - Liver transplantation (OLTx) is a procedure offered to individuals with advanced liver disease who are expected to live less than a year. Despite improvement in the care of transplant recipients, these patients are exposed to large volumes of blood and, as a result, are at risk to acquire hepatitis. Currently, the only vaccines available for the prevention of hepatitis are those that induce a response to HBsAg. In this study, 144 patients awaiting OLTx and 15 controls were vaccinated three times, once a month, intramuscularly in the deltoid using the Merck Hepatovax plasma-derived vaccine. This schedule was continued regardless of whether or not OLTx occurred before the series was completed. For the 15 controls, the response rate was 93% and for individuals with end-stage liver disease, it ranged from 44 to 54% (P less than 0.004). No difference in the percentage of those developing antibody was detected between groups based upon disease indication or whether the vaccination series was completed before or after OLTx. Of the following: WBC, lymphocytes (percent and number), CD3+ cells (percent and number), CD4+ cells (percent and number), CD8+ cells (percent and number), CD4+/CD8+ ratio, and B cells (percent and number), only the absolute WBC (P less than 0.05) distinguished between those who did and did not develop antibody.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1499448 TI - Early stages of gallstone formation in guinea pig are associated with decreased biliary sensitivity to cholecystokinin. AB - The purpose of this study was to measure differences in gallbladder sensitivity to cholecystokinin (CCK) in vivo during the early stages of gallstone formation and to correlate these findings to gallbladder CCK receptors. Guinea pigs were placed on either a normal diet or a two-week cholelithogenic diet, after which gallbladder emptying pressure to exogenously administered CCK was measured in vivo, according to the presence or absence of gallstones. At all doses of CCK tested (except 10(-10) mol/kg), the gallbladder response to CCK of guinea pigs that did not develop gallstones (on the cholelithogenic diet) was more sensitive than that of guinea pigs that did develop gallstones. Neither group was different from guinea pigs on a normal diet. In a second experiment, CCK receptors were measured on gallbladder muscularis from guinea pigs after two weeks on the same diet as in the first experiment. Those guinea pigs that did not develop gallstones had greater concentrations of CCK receptors (149 +/- 9 fmol/mg protein) than those that did develop gallstones (70 +/- 23 fmol/mg protein). Neither group was different from normal diet guinea pigs (119 +/- 57 fmol/mg protein). At the time point measured, there were no differences in the lipid chemistry or protein concentrations of gallbladder bile between the guinea pigs on the cholelithogenic diet that did or did not develop gallstones, or those on normal guinea pig chow. We conclude that the early stages of gallstone formation in guinea pigs are associated with decreased gallbladder sensitivity to CCK and that this change may be due to a lower concentration of CCK receptors on the gallbladder smooth muscle. PMID- 1499450 TI - Hepatitis B vaccine response before and after transplantation in 55 extrahepatic biliary atresia children. AB - Fifty-five children with cholestatic cirrhosis due to extrahepatic biliary atresia received a course of hepatitis B vaccine. Forty-seven received a plasma derived vaccine and eight a recombinant vaccine. Antibody determination was evaluated before and after liver transplantation in 30 patients. Twenty-five additional patients had antibody determination after transplantation only. Protection against hepatitis B was observed in 73.3% of the children evaluated prior to transplantation. One to 15 months after transplantation, 54.6% of all children studied showed protective levels of anti HBs. We conclude that hepatitis B vaccination is efficient in inducing immunity in the majority of children with cholestatic cirrhosis. Some patients will loose immunity under immunosuppression, but the protection rate remains higher than reported for patients vaccinated after transplantation. PMID- 1499451 TI - Reactivation of precore mutant hepatitis B virus leading to fulminant hepatic failure following cytotoxic treatment. AB - Three hepatitis B virus carriers who were HB(e)Ag negative and having normal liver function developed fulminant hepatitis with evidence of HBV replication following intensive chemotherapy for non-Hodgkin's lymphoma. Each was continuously negative for HB(e)Ag. Analysis of the precore region of HBV isolated from each demonstrated that the HBV of each had a point mutation in the precore region that inhibited the synthesis and the release of hepatitis B(e) antigen. This observation suggests that all HB carriers receiving either immunosuppressive or cytotoxic therapy should be monitored closely even if standard assays suggest that viral replication is not present. Sudden enhanced replication of a HBV mutant as a result of such therapy can be a cause of either very severe hepatitis or occasionally fulminant hepatitis. PMID- 1499452 TI - Changes in ultrastructure of hepatocytes and liver test results before, during, and after treatment with interferon-beta in patients with HB(e)Ag-positive chronic active hepatitis. AB - We studied the histological and ultrastructural changes in the liver and alterations in the liver test results before, during, and after treatment with human interferon-beta from five patients with hepatitis B e antigen-positive chronic active hepatitis. A daily dose of 3 x 10(6) to 6 x 10(6) units of interferon-beta was given intravenously for four weeks. The total index of periportal and portal inflammation, intralobular degeneration, and focal necrosis before treatment was decreased significantly six months after treatment (P less than 0.05). Ultrastructurally, the structure of endoplasmic reticulum was irregularly shaped or fragmentally decreased during treatment, but these disappeared six or 12 months after treatment. Glycogen particles diminished greatly during treatment. The alanine aminotransferase concentrations in these patients increased during treatment. Serum albumin and cholinesterase levels decreased significantly at the fourth week of treatment (P less than 0.01) and at the third day (P less than 0.01) to the second week (P less than 0.05) of treatment, respectively. These results suggest that interferon-beta injures endoplasmic reticulum and glycogen areas and damages the cholinesterase activity in the early stage of treatment and protein synthesis in patients with hepatitis B e antigen-positive chronic active hepatitis. PMID- 1499453 TI - Misoprostol hepatoprotection against ischemia-reperfusion-induced liver injury in the rat. AB - The hepatoprotective effects of misoprostol, a PGE1 analog, against ischemia reperfusion liver injury were studied using a rat partial liver ischemia model. Serum ornithine carbamoyltransferase (OCT) and alanine aminotransferase (ALT) levels were determined as biochemical indices of injury. Hepatic cell necrosis was assessed histologically using tetranitroblue tetrazolium (TNBT) and hematoxylin and eosin (H&E) staining. With placebo treatment, 90 min of partial hepatic ischemia followed by 24 hr of reperfusion resulted in increased levels of serum OCT (760 +/- 521 IU/liter) and ALT (4327 +/- 1982 IU/liter), while extensive hepatic necrosis was evident by TNBT and H&E staining. Treatment with two doses of 25 micrograms misoprostol/kg body weight at 1 min before ischemia and 1 min before reperfusion significantly reduced the serum levels of OCT and ALT (207 +/- 189 IU/liter, P less than 0.01 and 2075 +/- 1217 IU/liter, P less than 0.01, respectively) and hepatic necrosis. When a single dose of misoprostol was administered 1 min before reperfusion, similar protective effects were observed. However, when the treatment of misoprostol was delayed to 1 min after reperfusion, significantly less hepatoprotection was seen. Misoprostol exerted no hepatoprotection at all when it was administered at 5 min or later after reperfusion. These results demonstrate that misoprostol partially protects the liver against ischemia-reperfusion injury in the rat. The observation that the protective effect of misoprostol occurs only within the first minute of reperfusion suggests that its mechanism of action involves an early event in reperfusion injury, such as modifying the effects of reactive oxygen metabolites. PMID- 1499454 TI - Nonessential role of leukotrienes as mediators of acute gastric mucosal injury induced by aspirin in rats. AB - The present study was designed to determine the role of leukotrienes in aspirin induced acute gastric mucosal injury in rats. We examined the effects of aspirin, indomethacin, and sodium salicylate on gastric mucosal injury, and on eicosanoid synthesis and content. Aspirin, indomethacin, and acidified salicylate caused significant mucosal injury, while salicylate at pH 7 did not induce significant injury. Aspirin and indomethacin significantly reduced mucosal prostaglandin synthesis and content. No significant changes in mucosal leukotriene C4 synthesis and content were observed. There were no correlations between changes in mucosal leukotriene B4 synthesis and the extent of mucosal injury. We also evaluated the effects of MK-571 (a leukotriene D4 receptor antagonist) and MK-886 (a leukotriene biosynthesis inhibitor) on aspirin-induced gastric mucosal injury. Neither MK-571 nor MK-886 could reduce the mucosal lesions induced by aspirin. These findings suggest that leukotrienes are not involved in aspirin-induced acute gastric mucosal injury in rats. PMID- 1499455 TI - Acute typhlitis in an immunocompromised host. Report of an unusual case and review of the literature. AB - A case of acute typhlitis arising in a neutropenic male is described. Light and electron microscopy reveal findings resembling those of an early stage of malakoplakia. The coexistence of these two uncommon lesions suggests a pathogenetic role in the development of septicemia in immunocompromised hosts. PMID- 1499456 TI - Heterotopic mucinous cystadenoma of the pancreas. AB - A 46-year-old female who had been experiencing severe diarrhea and marked weight loss underwent exploratory laparotomy because of a mass near the tail of the pancreas noted on CT scan. Pathologic examination revealed a mucinous cystadenoma of the pancreas occurring in heterotopic pancreatic tissue. This is the second reported case of mucinous cystadenoma occurring in heterotopic pancreatic tissue. PMID- 1499457 TI - New PC-based program to calculate gastric secretion and emptying using a marker dilution technique. PMID- 1499458 TI - Autoimmune gastritis: is Helicobacter pylori a merely commensal or a pathogenic agent? PMID- 1499459 TI - Antroduodenal manometry. PMID- 1499460 TI - Measurement of health status in diabetic patients. Diabetes impact measurement scales. AB - OBJECTIVE: To develop an instrument to measure health status in adult insulin dependent (type I) and non-insulin-dependent (type II) diabetic patients. RESEARCH DESIGN AND METHODS: Correlative study to examine psychometric properties of the questionnaire. Test-retest reliability, item-scale correlations, principal components analysis, correlations with global clinical ratings, and correlations with clinical data extracted from medical records were examined at the diabetes clinics at the University of California, Davis, Medical Center. Patients were volunteer clinic patients able to complete the questionnaire. One hundred thirty patients completed a first administration of the questionnaire, and 52 completed a second administration. RESULTS: Test-retest reliability was satisfactory. Item scale correlations showed that 40 of 44 questionnaire items were highly correlated with subscale and total scale scores. Principal-components analysis identified one major factor measured by the questionnaire. Cronbach's alpha, a measure of the scales' internal consistency, was of satisfactory magnitude. Global ratings of clinical status by patients and clinicians were highly correlated with scale scores. Correlations of scale scores with clinical data were generally of low magnitude but, where significant, were consistently in the direction hypothesized if the scale truly measures health status or disease impact. CONCLUSIONS: The Diabetes Impact Management Scales (DIMS) is an easily administered questionnaire with internal consistency and test-retest reliability. Preliminary correlative analyses support the validity of the instrument as a measure of health status in adult type I and type II diabetic patients. Further work will be necessary to firmly establish the validity of the DIMS and its usefulness in clinical outcomes research. PMID- 1499461 TI - alpha-Glucosidase inhibition by miglitol in NIDDM patients. AB - OBJECTIVE: To determine the efficacy of the alpha-glucosidase inhibitor miglitol (BAYm 1099) regarding the starch content of food. RESEARCH DESIGN AND METHODS: Thirty-six non-insulin-dependent diabetes mellitus (NIDDM) subjects were studied in a double-blind randomized study comparing treatment with a single dosage of 100 mg miglitol or placebo and a single-blind crossover comparison of three test meals in which the carbohydrate contained either 30, 50, or 70% starch, and quantities of fat and protein were kept constant. RESULTS: Postprandial blood glucose excursions were reduced by approximately 50% with miglitol after all test meals. In contrast, after miglitol treatment, maximum postprandial serum C peptide and insulin values reached the same levels as after placebo treatment, although the time to reach these maximum levels was delayed. Free fatty acid values decreased after both miglitol and placebo similarly. Twenty-eight untoward events in 15 patients were reported in the miglitol treatment group and 11 events in 7 patients in the placebo treatment group. CONCLUSIONS: Miglitol reduces postprandial blood glucose excursions independent of the starch content of the meal. Because no effects were found on incremental postprandial maximal levels of serum insulin and C-peptide, it may be that miglitol exerts, in addition to a delay of intestinal carbohydrate absorption, extraintestinal effects as well, particularly effects on disposition of glucose or anti-insulin counterregulatory factors. PMID- 1499462 TI - Prevalence and health-care features of hyperglycemia in semiurban-rural communities in southern Saudi Arabia. AB - OBJECTIVE: To determine the prevalence of hyperglycemia in semiurban-rural Saudi Arabian communities and to assess some of its important health-care related aspects. RESEARCH DESIGN AND METHODS: A cluster of 12 villages near the city of Abha, the capital of the southern region in Saudi Arabia, with a total population of 2150 (290 families) has been included in this study. The family head was interviewed about diagnosed diabetes among family members. Also, the capillary blood glucose level was measured in subjects greater than or equal to 10 yr (the target population, n = 1419) with a reflectance meter after 2-h fasting after the main midday meal. RESULTS: The 87% of the target population who responded for screening showed a prevalence of 4.6% of diabetes, which was higher among men (5.5%, age adjusted, P less than 0.05) than among women (3.6%). Estimates were based on 57 cases ascertained by positive history of the disease (n = 49) or blood glucose level greater than 11.1 mM (200 mg/dl) without previous diagnosis of diabetes (n = 8). The prevalence of impaired glucose tolerance (blood glucose between 7.8 (140 mg/dl) and 11.0 mM (199 mg/dl) with no history of diabetes) was 3.7%, being higher among women than among men (P less than 0.01). Eighty-eight percent of the previously diagnosed cases were receiving treatment at the time of screening. However, in only 12.2% of those receiving treatment was glucose found to be controlled (level less than 7.8 mM [140 mg/dl]). CONCLUSIONS: Diabetes frequency in this Saudi community is relatively high. There is a pressing need to promote public awareness about the disease and to improve the competency of the health-care team for achieving better control and early detection of the disease. PMID- 1499463 TI - Urinary excretion of IGF-I and growth hormone in children with IDDM. AB - OBJECTIVE: To compare the urinary output of insulinlike growth factor I (IGF-I) and growth hormone (GH) in prepubertal and pubertal children with insulin dependent diabetes mellitus (IDDM) versus nondiabetic subjects and to analyze the relationship between the urinary excretion of these peptides and degree of metabolic control. RESEARCH DESIGN AND METHODS: Group 1 included 30 IDDM patients who had had diabetes for 4.9 +/- 0.7 yr and had normal renal function (mean age 11.6 +/- 0.9 yr); group 2 consisted of 31 control subjects (mean age 9.2 +/- 0.6 yr). Sensitive radioimmunoassays were used to measure IGF-I and GH in urine aliquots from 12-h timed overnight collections that had been dialyzed, concentrated 50-fold, and lyophilized. RESULTS: Significantly lower IGF-I and GH outputs per kilogram body weight per 12 h were observed in IDDM subjects compared with control subjects. When data were expressed per kilogram of body weight, no difference was observed between the urinary output of IGF-I and GH between prepubertal and pubertal subjects within group 1 or group 2. The prepubertal children had significantly lower HbA1 than the pubertal population; however, no correlation was found between urinary output of IGF-I or GH and HbA1. A positive correlation was observed between urinary IGF-I and GH (r = 0.85, P less than .001). CONCLUSIONS: Patients with long-standing IDDM excrete significantly lower urinary levels of IGF-I and GH compared with normal subjects. Serial measurements of these peptides from onset of IDDM are needed to define whether the changes observed are present at diagnosis or are secondary to duration of disease. PMID- 1499464 TI - Microalbuminuria in type I diabetic patients. Prevalence and clinical characteristics. AB - OBJECTIVE: To estimate the prevalence of microalbuminuria, overnight urinary albumin excretion rate (AER) greater than or equal to 30 and less than or equal to 250 micrograms/min, in a large sequential sample of nonhypertensive insulin dependent (type I) diabetic patients attending hospital diabetic clinics, to identify micro- and normoalbuminuric patients in this sample for subsequent intervention and natural history follow-up studies, and to compare the clinical characteristics of the micro- and normoalbuminuric patients identified. RESEARCH DESIGN AND METHODS: Screening was conducted in two phases. In phase 1, all eligible patients were asked to provide an early morning urine specimen for measurement of albumin concentration and albumin-creatinine ratio. In phase 2, all patients with an albumin concn greater than or equal to 15 mg/L and/or an albumin-creatinine ratio greater than or equal to 3.5 mg/mmol and a random sample of those with an albumin concn less than 15 mg/L and albumin-creatinine ratio less than 3.5 mg/mmol were asked to collect a timed overnight urine specimen for determination of AER. RESULTS: Among 1888 patients (16-60 yr old, diabetes onset less than 40 yr, and duration of diabetes less than 35 yr) who were screened, the prevalence of microalbuminuria was approximately 3.7% (95% confidence interval (CI) 2.7-7.6%). Duration of diabetes was significantly longer in micro- than normoalbuminuric patients (20 vs. 15 yr, respectively; P less than 0.001), and in no patient with microalbuminuria was the duration of diabetes less than 5 yr. Systolic and diastolic blood pressures, higher in micro- than normoalbuminuric patients (132 vs. 122 mmHg, P less than 0.01; 77 vs. 72 mmHg, P less than 0.01), were strongly associated with AER. CONCLUSIONS: Microalbuminuria in type I diabetes, which appears to represent an earlier phase in the development of clinical nephropathy, is associated with elevated blood pressure and a longer duration of diabetes. PMID- 1499466 TI - Impact of associated conditions on glycemic control of NIDDM patients. AB - OBJECTIVE: To assess the impact of associated conditions (obesity, dyslipidemia, and hypertension) on the glycemic control of non-insulin-dependent diabetes mellitus (NIDDM) patients under home-life conditions. RESEARCH DESIGN AND METHODS: We analyzed the metabolic data of 271 NIDDM patients (89% Mexican American) screened in a population-based survey (the San Antonio Heart Study). RESULTS: Obesity was present in 77% of the patients, hypertension in 23%, hypertriglyceridemia (serum triglycerides greater than 2.9 mM) in 23%, and hypercholesterolemia (serum total cholesterol greater than 6.5 mM) in 14%. Forty percent of the patients had two or more comorbid conditions. With the use of a multiple linear regression model, which was adjusted for age, sex, ethnicity, distribution of body fat (waist-hip ratio), plasma insulin, and treatment (of both diabetes and hypertension), we found that the presence of higher serum triglyceride concentrations was associated with significantly higher plasma glucose levels both in the fasting state (1.4 mM, P less than 0.001) and 2 h after an oral glucose load (1.2 mM, P = 0.003). The presence of obesity, hypertension, or high serum cholesterol levels was not associated with significant changes in glycemic control. When the entire group was stratified by diabetes treatment (untreated n = 89, diet n = 75, oral agents n = 82, insulin n = 25) and after adjusting for age, sex, ethnicity, and waist-hip ratio, only fasting and 2-h plasma glucose and insulin concentrations were significantly different across treatment groups, with diet and oral agents being associated with higher fasting (P less than 0.001) and postglucose (P less than 0.005) plasma glucose levels and lower plasma insulin concentrations (P less than 0.005) compared with newly diagnosed patients. Neither serum lipids nor blood pressure differed across treatment. CONCLUSIONS: In NIDDM patients under home-life conditions, higher serum triglycerides are associated with higher fasting and postglucose hyperglycemia regardless of antidiabetic treatment. The presence of obesity, hypertension, or high serum cholesterol levels is not associated with significant changes in glycemic control. PMID- 1499465 TI - Glycemic control and peripheral nerve conduction in children and young adults after 5-6 mo of IDDM. Wisconsin Diabetes Registry. AB - OBJECTIVE: A cohort of people (n = 86) was examined in the first few months after insulin-dependent diabetes mellitus (IDDM) diagnosis to evaluate the effect of hyperglycemia on nerve conduction velocities and latencies. RESEARCH DESIGN AND METHODS: Unselected cases with IDDM, who were 6-29 yr of age, were identified at diagnosis from a large, geographically defined area of southern Wisconsin. Peripheral nerve conduction was measured on a sample from this cohort. RESULTS: Peroneal nerve conduction velocity was significantly inversely related to glycosylated hemoglobin (P less than 0.05, age and height adjusted). All other nerve conduction velocities and latencies (median motor, median sensory, and sural) showed the same tendency, but the associations were not statistically significant. Twenty-four-hour urine C-peptide and duration of diabetes (3-11 mo) were not consistently related to nerve conduction parameters after controlling for age and height. CONCLUSIONS: These findings suggest that as early as 5-6 mo after diabetes diagnosis, and at a time frequently characterized by partial remission of IDDM, hyperglycemia has a role in the acute slowing of nerve conduction velocity. Other factors such as residual endogenous insulin production do not appear to influence these early changes. PMID- 1499467 TI - Incidence of IDDM in Western Australia in children aged 0-14 yr from 1985 to 1989. AB - OBJECTIVE: To document the incidence of insulin-dependent diabetes mellitus (IDDM) in Western Australia in children aged 0-14 yr between 1985 and 1989 and to test for differences in incidence by year of diagnosis, age of diagnosis, and sex. RESEARCH DESIGN AND METHODS: A population-based register that used a primary source of case ascertainment (diabetes clinics at teaching hospitals and direct approach to general practitioners and general physicians) and a secondary source (Western Australian Hospital Morbidity Data System) established numerator data. Denominator data were obtained from the Australian Bureau of Statistics. RESULTS: From 1985 to 1989 inclusive, 235 children in the 0- to 14-yr age-group were diagnosed with IDDM in Western Australia. Case ascertainment was estimated at 99% complete. The mean age-adjusted (developed-world population) annual incidence of IDDM was 13.2 per 100,000 person-yr and there was no evidence of an increasing incidence over the 5 yr. However, girls were more likely than boys to be diagnosed with IDDM in this period (P = 0.006). CONCLUSIONS: The incidence of IDDM in Western Australia is in the middle range of IDDM incidence in countries throughout the world. The unexpected finding of an increased incidence of IDDM in girls compared with boys needs to be confirmed in a future study. PMID- 1499468 TI - Psychosocial state of patients with IDDM prone to recurrent episodes of severe hypoglycemia. AB - OBJECTIVE: The aim of this study was to investigate the psychosocial situation in patients with insulin-dependent diabetes mellitus (IDDM) with recurrent attacks of severe hypoglycemia (SH). RESEARCH DESIGN AND METHODS: The study group consisted of 17 adult patients with SH and 17 patients matched to the study group with regard to sex, age, and duration of diabetes without severe attacks. The psychosocial situation was measured by means of self-rated questionnaires and an observer's rating scale. RESULTS: Parameters such as social support, life events, type A behavior, neuroticism, and vital exhaustion were not different, although a higher anxiety rating (P less than 0.05) and a lower rating of happiness (P less than 0.01) were found in the SH group. CONCLUSIONS: We conclude that the anxiety level is increased and that experienced happiness is decreased in patients prone to recurrent severe hypoglycemia. PMID- 1499469 TI - Pittsburgh Epidemiology of Diabetes Complications Study. Measuring diabetic neuropathy follow-up study results. AB - OBJECTIVE: This project evaluated the utility of quantitative sensory techniques in predicting the development of neuropathy for subjects participating in a prospective study. RESEARCH DESIGN AND METHODS: Distal symmetric polyneuropathy was evaluated in 77 insulin-dependent diabetes mellitus individuals via quantitative sensory testing, nerve conduction studies, and clinical examination. RESULTS: Although the specificity and positive predictive value were low for the quantitative sensory techniques as predictors of neuropathy diagnosed on clinical exam approximately 2 yr later, the sensitivity for vibratory thresholds was high (100%). Variability over the 2-yr interval was shown on follow-up testing for each of the objective assessment modalities and it was not explained by differences for potential risk factors measured at baseline. CONCLUSION: Despite a cross-sectional relationship between the assessment modalities and clinically overt neuropathy at baseline, these follow-up data suggest that the potential for the objective modalities as predictors of clinically diagnosed neuropathy may be limited. PMID- 1499470 TI - Microalbuminuria associated with diabetic neuropathy. AB - OBJECTIVE: To test the hypothesis that microalbuminuria may show an independent statistical association with diabetic neuropathy. RESEARCH DESIGN AND METHODS: An observational study of a prospectively identified cohort was conducted at the University Medical Center. The cohort consisted of 78 consecutive diabetic patients who fulfilled the criteria of having diabetes for greater than 10 yr, a normal serum creatinine, urine negative for macroalbuminuria by a commonly used dipstick method, a blood glucose less than 13.8 mM (less than 250 mg/dl), and an HbA1 less than 11% (normal range 5.5-8.5%). Medical record review established the presence of chronic complications of diabetes. Urine albumin level was measured by radioimmunoassay. Albumin concn greater than or equal to 15 mg/L was used as a cutoff value for microalbuminuria. RESULTS: Twenty-five of 78 patients (32%) showed microalbuminuria. Of these, 51% had neuropathy, 39% had retinopathy, 35% arterial hypertension, 17% peripheral vascular disease, and 15% ischemic heart disease. After adjusting for age, sex, and type and duration of diabetes, diabetic neuropathy and hypertension showed a significant association with microalbuminuria. After adjusting for other diabetic complications, diabetic neuropathy showed a significant association with microalbuminuria. CONCLUSIONS: Microalbuminuria is independently associated with diabetic neuropathy. This association lends support to the theory of a vascular etiology for diabetic distal symmetrical neuropathy. PMID- 1499471 TI - Somatosensory conduction delay in central and peripheral nervous system of diabetic patients. AB - Fifty-four diabetic patients with or without clinical evidence of neuropathy and with no clinical evidence of CNS dysfunction were studied by somatosensory-evoked potentials after electrical stimulation of the median nerve at the wrist and recorded from the scalp electrode against a noncephalic reference. Peripheral conduction index, calculated as the distance from the wrist to the C7 spinous process divided by the P9 latency, was significantly decreased (P less than 0.01) in diabetic patients (69.81 +/- 6.47 m/s) compared with 28 age-matched nondiabetic subjects (76.85 +/- 5.65 m/s). The P11-P13 interpeak latency, representative of the transit time from the dorsal column at the level of the sensory input into the cervical cord to the brain stem along the somatosensory pathways (CCT1), and the P13-N19 interpeak latency, representative of the transit time from the brain stem to the somatosensory cortex (CCT2), were significantly increased in diabetic patients (CCT1, 2.51 +/- 0.63 ms; CCT2, 5.76 +/- 0.92 ms) compared with nondiabetic subjects (CCT1, 2.28 +/- 0.36 ms, P less than 0.05; CCT2, 5.18 +/- 0.51 ms, P less than 0.01). We conclude that, in diabetic patients, neurophysiological abnormalities may be present in two distinct parts of the CNS and the peripheral nervous system. PMID- 1499472 TI - Accuracy of home blood glucose monitors. AB - OBJECTIVE: To determine the accuracy of five home blood glucose monitors (HBGM) in reference to a standard laboratory reference method. RESEARCH DESIGN AND METHODS: The study took place in the laboratory of a 350-bed private acute-care hospital. Subjects were a sample of convenience of 207 diabetic and nondiabetic adult and pediatric patients scheduled for fasting blood work that included a blood glucose test. Venous blood samples were collected for laboratory determination of blood glucose level. A separate sample was collected for testing on two each of five HBGMs: AccuChek II M, Tracer II, ExacTech, Glucometer II with Memory, and One Touch. RESULTS: Multiple regression analysis showed that all 10 monitors could be used to predict laboratory blood glucose values. The monitors with the highest predictabilities were One Touch, Tracer II, and AccuChek II M. Consistency between monitors of the same brand was lowest with One Touch. AccuChek II M had the smallest SD between the 2 monitors used in the study. CONCLUSIONS: HBGM can be used to predict actual laboratory values of blood glucose. However, the controlled environment of the study should be considered and patient education made a high priority when recommending monitors. PMID- 1499473 TI - Comparison of combined therapies in treatment of secondary failure to glyburide. AB - OBJECTIVE: To compare the effectiveness of alternative combined treatments in patients with non-insulin-dependent diabetes mellitus (NIDDM) with secondary failure to sulfonylureas. RESEARCH DESIGN AND METHODS: A crossover study was carried out by randomly assigning 16 NIDDM patients to a combined treatment with the addition of either a single low-dose bedtime injection of 0.2 U/kg body wt NPH insulin or an oral three times a day administration of 1.5 g/day metformin to the previously ineffective glyburide treatment. RESULTS: Both combined therapies significantly (P less than 0.01) reduced fasting plasma glucose (FPG), postprandial plasma glucose (PPPG) and percentage of HbA1. The addition of metformin was more effective than the addition of insulin (P less than 0.01) in improving PPPG in the 8 patients with higher post-glucagon C-peptide levels. In contrast, the efficacy of neither combined therapy was related to patient age, age of diabetes onset, duration of the disease, percentage of ideal body weight, and FPG. The addition of insulin but not metformin caused a significant (P less than 0.01) increase of mean body weight. Neither combined treatment caused changes in serum cholesterol and triglyceride levels. No symptomatic hypoglycemic episode was reported in any of the 16 patients. CONCLUSIONS: The addition of bedtime NPH insulin or metformin was effective in improving the glycemic control in most NIDDM patients with secondary failure to glyburide. The combination of metformin and sulfonylurea was more effective in reducing PPPG and did not induce any increase of body weight. PMID- 1499474 TI - Erythrocyte spermidine levels in IDDM patients. AB - OBJECTIVES: To evaluate whether erythrocyte levels of polyamines spermidine and spermine (expressed in nmol/ml packed erythrocytes [PRBCs]) are modified in insulin-dependent diabetes mellitus (IDDM) and are associated with the presence of retinopathy or nephropathy. RESEARCH DESIGN AND METHODS: We studied erythrocyte spermidine and spermine levels in 38 IDDM patients with or without persistent microalbuminuria (urinary albumin excretion rate [AER] between 20 and 200 micrograms/min), macroalbuminuria (AER greater than 200 micrograms/min), or retinopathy compared with 60 sex- and age-matched control subjects. RESULTS: Mean +/- SD erythrocyte spermine content was similar in both diabetic (9.7 +/- 5.5 nmol/ml PRBCs) and control (8.8 +/- 3.5 nmol/ml PRBCs) subjects, whereas spermidine was higher in diabetic (19.1 +/- 7.2 nmol/ml PRBCs) than in control (14.5 +/- 4 nmol/ml PRBCs, P = 0.0007) subjects. Moreover, spermidine was significantly higher in the groups with microalbuminuria (n = 11, 22.5 +/- 9.2 nmol/ml PRBCs) and macroalbuminuria (n = 4, 22.2 +/- 5.7 nmol/ml PRBCs) than in both normoalbuminuric (n = 23, 16.9 +/- 5.6 nmol/ml PRBCs) and control (F = 9.78, P = 0.0001) subjects, and correlated with log AER (r = 0.41, P = 0.009). Similarly, proliferative retinopathy was associated with a significant increase in spermidine (n = 5, 20 +/- 7 nmol/ml PRBCs compared with control subjects [P = 0.0009]). CONCLUSIONS: Our data suggest that erythrocyte spermidine content is increased in IDDM patients associated with both diabetic nephropathy and advanced retinopathy. PMID- 1499475 TI - Short-term effect of red wine (consumed during meals) on insulin requirement and glucose tolerance in diabetic patients. AB - OBJECTIVE: To determine the effect of wine on insulin requirement or glucose tolerance. RESEARCH DESIGN AND METHODS: Five men with insulin-treated diabetes and 10 men with non-insulin-treated diabetes ate the same lunch with the same volume of either water or red wine (2 glasses). Insulin requirement was determined with an artificial pancreas (Biostator). Glucose tolerance was evaluated from the postprandial glycemic level. RESULTS: There was no significant difference in insulin requirement determined with an artificial pancreas in the insulin-treated patients after the two meals (31.5 +/- 4.21 U with water and 31.8 +/- 4.3 U with wine). Glucose tolerance in the non-insulin-treated patients was lower after the meal with wine. CONCLUSIONS: Moderate prandial wine consumption has no adverse effect on the glycemic control of diabetic patients. Thus, it appears unnecessary to proscribe the consumption of red wine in moderation with meals to diabetic patients. Wine contains tannins and phytates that can explain its action. PMID- 1499476 TI - Role of industry representatives in providing assistance to certified diabetes educators. AB - OBJECTIVE: As diabetes educators have become more frequently involved in decisions regarding medications, equipment, and supplies, industry representatives have increasingly provided various types of assistance. The major objectives of this survey were to determine 1) the types of assistance being provided to certified diabetes educators (CDEs) by industry representatives, 2) whether product recommendations are based on assistance provided, and 3) the types of assistance that CDEs consider appropriate. RESEARCH DESIGN AND METHODS: We developed the survey instrument and it was mailed to every fifth person listed in the 1989 directory of CDEs. Three hundred twenty-five (51%) of the active surveys were returned. RESULTS: Those responding indicated that 1) the types of support provided most frequently by industry representatives include instructional materials, samples, supplies, and equipment for patient care and education; 2) the number of types of support provided is directly related to the number of industry representatives seen on a regular basis and the frequency of interaction; 3) 22% of the educators state that they make product recommendations based on support provided; and 4) the role of the industry reps should be to continue support for patient care and education, to provide more support for public and professional education, and to minimize support for personal items, e.g., gifts or meals. CONCLUSIONS: The survey indicates that CDEs are receiving many types of assistance from industry representatives and that they prefer that such assistance be targeted toward patient and professional education. PMID- 1499477 TI - Vascular endothelial cell antibodies in diabetic patients. Association with diabetic retinopathy. AB - OBJECTIVE: To determine the incidence of antiendothelial cell antibodies in diabetic patients with and without retinopathy. RESEARCH DESIGN AND METHODS: The study consisted of 70 insulin-dependent diabetic (IDDM) subjects, 36 non-insulin dependent diabetic (NIDDM) subjects, and 40 nondiabetic control subjects. Blood samples were obtained from diabetic patients and control subjects and patients with background and proliferative retinopathy were identified. RESULTS: Vascular endothelial cell (VEC) antibodies were examined in the sera of 36 NIDDM subjects, 70 IDDM subjects, and 40 nondiabetic control subjects by indirect immunofluorescence. VEC antibodies were present in 5 of 40 (12%) control subjects, 7 of 23 (30%) newly diagnosed IDDM patients, 6 of 17 (35%) IDDM patients without retinopathy, 12 of 18 (67%) IDDM patients with background retinopathy (P less than 0.05), and 9 of 12 (75%) IDDM patients with proliferative retinopathy (P less than 0.01). Three of 13 (23%) NIDDM patients with retinopathy and 6 of 23 (26%) without retinopathy were VEC antibody positive. No associations were observed between the presence of VEC antibodies and either the quality of glycemic control or the duration of diabetes. A significant association between VEC antibodies and large-vessel disease was found in IDDM patients with retinopathy (P less than 0.05). CONCLUSIONS: Antibodies directed against vascular endothelial cells may play a role in the development of microvascular, and possibly macrovascular, disease in diabetes. PMID- 1499478 TI - Relationship between plasma insulin and blood pressure in South African black women in Johannesburg. AB - OBJECTIVE: To examine the relationship between fasting plasma insulin and blood pressure (BP) in 40 urbanized normotensive South African black women aged 24-60 yr, and to assess the effects of body mass index (BMI) and fasting plasma glucose on BP. RESEARCH DESIGN AND METHODS: The women comprised equal numbers of young nonobese nondiabetic subjects, middle-aged nonobese nondiabetic subjects, middle aged obese nondiabetic subjects, and middle-aged obese newly diagnosed non insulin-dependent diabetic subjects. Systolic and diastolic BPs were recorded (in duplicate) after 15 min of recumbency, and fasting plasma glucose and insulin levels were determined thereafter. The data were analyzed by simple and multivariate regression. RESULTS: There was a wide distribution of individual physical and biochemical features. With simple correlations, systolic BP correlated significantly with age, BMI, and fasting glucose but not with insulin. Diastolic BP correlated significantly with all four variables (r = 0.37, P less than 0.05). When adjusted for age, BMI, and glucose, however, the significant correlation between diastolic BP and insulin diminished (r = -0.04). CONCLUSIONS: As in other nonwhite communities, plasma insulin does not appear to play a major role in regulating the BP of South African black women. PMID- 1499479 TI - Sex differences in secondary attack rate of IDDM to siblings of probands through older ages. Pittsburgh Etiology of IDDM Study. AB - OBJECTIVE: To determine the descriptive epidemiological patterns of the secondary attack rate of insulin-dependent diabetes mellitus (IDDM) among siblings of probands through older ages. RESEARCH DESIGN AND METHODS: A family history analysis was performed on 1774 IDDM probands who were diagnosed or seen within 1 yr of diagnosis at Children's Hospital of Pittsburgh from 1 January 1950 through 31 December 1981. The probands were discharged on insulin and were diagnosed at less than 17 yr of age. The time frame permitted the risk of IDDM for siblings of probands to be calculated over a broad spectrum of age. RESULTS: Risk estimates for the 3966 full natural siblings through 10, 20, and 30 yr of age were 1.6, 4.1, and 6.3%, respectively. Secondary attack rates were equivalent for male and female siblings through 15 yr of age (3%); however, the risk to males increased an additional 4% between 16 and 30 yr of age compared with 2.5% for females (P = 0.01). There was no evidence of an excess sex concordance among affected sibling pairs. CONCLUSIONS: Males have a greater secondary attack rate of IDDM at older ages than females. This may be due to an increased exposure to environmental agents among males or protective influences operating among females. PMID- 1499481 TI - Truth or consequences. PMID- 1499480 TI - Beneficial effect of low-glycemic index diet in overweight NIDDM subjects. AB - OBJECTIVE: To determine whether low-glycemic index (GI) diets have clinical utility in overweight patients with non-insulin-dependent diabetes mellitus (NIDDM). RESEARCH DESIGN AND METHODS: Six patients with NIDDM were studied on both high- and low-GI diets of 6-wk duration with metabolic diets with a randomized crossover design. Both diets were of similar composition (57% carbohydrate, 23% fat, and 34 g/day dietary fiber), but the low-GI diet had a GI of 58 compared with 86 for the high-GI diet. RESULTS: Small and similar amounts of weight were lost on both diets: 2.5 kg on high-GI diet and 1.8 kg on low-GI diet. On the low-GI diet, the mean level of serum fructosamine, as an index of overall blood glucose control, was lower than on the high-GI diet by 8% (P less than 0.05), and total serum cholesterol was lower by 7% (P less than 0.01). CONCLUSIONS: In overweight patients with NIDDM, reducing diet GI improves overall blood glucose and lipid control. PMID- 1499482 TI - The Department of Veterans Affairs Implanted Insulin Pump Study. PMID- 1499483 TI - Proposed federal food labeling regulations. Implication for diabetes education and care. PMID- 1499484 TI - Diabetes care reimbursement uncertain after Medicare reform. Physicians remain skeptical of resource-based relative value scales. PMID- 1499485 TI - Benefits of preventive programs in eye care are visible on the bottom line. A new nationwide effort to improve eye care for people with diabetes gets backing from a study on the cost-effectiveness of screening for retinopathy. PMID- 1499486 TI - Hypoglycemia. Frequency, severity, and consequences. PMID- 1499487 TI - Long-term neurological consequences of hypoglycemia. PMID- 1499488 TI - Human versus porcine insulin gone wrong. PMID- 1499489 TI - Microangiopathic ischemic myopathy of semimembranosus muscle in patient with diabetes mellitus. PMID- 1499490 TI - Effect of an aldose reductase inhibiting agent on limited joint mobility in IDDM. PMID- 1499491 TI - Mutations in insulin-receptor gene. Val996 allele in white NIDDM patients. PMID- 1499492 TI - Catheter obstruction with continuous subcutaneous insulin infusion. Effect of insulin concentration. PMID- 1499493 TI - How to motivate the team. It takes more than money. PMID- 1499494 TI - Getting the new staffer on track. PMID- 1499495 TI - Time is money. PMID- 1499496 TI - Basics of a good medical history form. How to protect the patient and prepare the staff. PMID- 1499497 TI - A closer look at chemical dependency. Dealing with co-workers who abuse drugs, drink. PMID- 1499498 TI - Do they compute? PMID- 1499499 TI - Save the children. PMID- 1499500 TI - The changing dental team. What employees want from their jobs, their employers. PMID- 1499501 TI - Automating your practice. PMID- 1499502 TI - High-tech comes to dentistry. Using sophisticated equipment to its fullest. PMID- 1499504 TI - How good are you at solving problems? Everyday situations in the office. PMID- 1499503 TI - Amalgam's contribution to dentistry: the real story. PMID- 1499505 TI - Taking a look at your recall system. PMID- 1499506 TI - [Reproduction medicine from the viewpoint of a psychiatric therapist. To what kind of life are we challenged by the modern reproduction techniques?]. PMID- 1499507 TI - [Teachers for the nursing professions. The current educational and professional situation of teachers for the nursing professions in Germany]. PMID- 1499508 TI - [The curriculum for teacher education for professional schools with special reference to the situation in the health professions]. PMID- 1499509 TI - [Nursing the septic patient]. PMID- 1499510 TI - [Catheter-associated septicemia]. PMID- 1499511 TI - [Organization and execution of bacteriological monitoring]. PMID- 1499512 TI - [Septicemia. Pathophysiology, clinical picture and treatment strategies from an anesthesiological viewpoint]. PMID- 1499513 TI - [The septic patient. Principles of surgical treatment]. PMID- 1499514 TI - [Problems of long-term care patients in intensive care units]. PMID- 1499515 TI - [Neonatal septicemia. Risk factors, microbial spectrum, clinical symptoms, diagnosis, therapy]. PMID- 1499516 TI - [Communicative didactics]. PMID- 1499517 TI - [Conflict didactics]. PMID- 1499518 TI - [Female characters in medieval nursing]. PMID- 1499519 TI - [Report of experiences on the use of ward secretaries]. PMID- 1499520 TI - [Myelodysplastic syndromes. The epidemiological and etiological aspects]. AB - From a total of 18,416 bone-marrow biopsy reports entered into the Dusseldorf Bone Marrow Registry between 1975 and 1990 those of patients diagnosed as having preleukaemia, myeloid dysplasia, panmyelopathy with hypercellular bone marrow, refractory anaemia, sideroblastic anaemia or smoldering leukaemia were reanalyzed together with patient-data. If the diagnosis of myelodysplastic syndrome (MDS) was confirmed, the original blood and bone-marrow smear was re-examined and classified, 584 cases in all (3.2%). During the same period acute myeloid leukaemia had been diagnosed in 506 patients (2.8%). The average annual incidence of MDS in the Dusseldorf area was 3.65 per 100,000 inhabitants. Over 80% of cases occurred from the age of 60 years, while 7% were younger than 50 years. The sex ratio was the same in all subgroups of MDS, except chronic myelomonocytic leukaemia (male:female ratio 1:1.57). 31 patients (5.3%) had received ionizing radiation and/or cytostatic or immunosuppressive treatment for various underlying diseases before MDS had been diagnosed (secondary MDS). Preceding occupational contact with organic solvents could not be excluded with certainty in 12 patients. These data suggest that MDS is a relatively frequent disease of hematopoiesis among the older age groups. The proportion of secondary (treatment induced) forms is small and does not explain the recently observed increased incidence. PMID- 1499521 TI - [The solitary pulmonary histoplasmoma]. AB - A 63-year-old man who grows orchids as a hobby, fell ill with weakness and pain in his hips and legs 2 months after his latest trip to South America (Ecuador). The WBC count was 9900/microliters with unremarkable differential count while blood sedimentation rate was raised to 60/100 mm. The chest X-ray demonstrated in the right upper lobe a well-circumscribed coin lesion (3 cm diameter) of soft tissue density, uncalcified and without cavitation. Computed tomography in addition revealed an enlarged lymph-node at the lower hilar pole, but no mediastinal lymphoma. Bronchoscopy demonstrated narrowing of a subsegmental ostium of the 6th segment on the right. An attempt at transbronchial biopsy failed. As a peripheral bronchial carcinoma was suspected, a posterolateral thoracotomy was performed (4 months after the trip to Ecuador). Rapid histological examination was negative for tumour and the lesion was therefore enucleated. Histologically (Grocott silver staining) a histoplasmoma was diagnosed. Several serum samples were positive for precipitating (M-band) and complement-binding antibodies (titre 12 days preoperatively was 1:16). The postoperative course was without complication. No anti-histoplasma antibodies were demonstrable 1 year postoperatively. PMID- 1499522 TI - [Toxic myopathy with kidney failure as a colchicine side effect ifn familial Mediterranean fever]. AB - A 24-year-old woman with familial Mediterranean fever (FMF) had for one year been treated with colchicine, 1 mg daily, for repeated bouts of fever, abdominal pain and arthritis. She was also known to have renal amyloidosis. Lately she had developed gastrointestinal symptoms, muscle pain and obvious, predominantly proximal muscular weakness in both legs. The cause of the symptoms was rhabdomyolysis with an increased creatinine activity of 1000 U/l and marked myoglobinuria (1600 micrograms/l), as well as renal failure with normal uric acid and a creatinine clearance of 3 ml/min per 1.73 m2. Serum creatinine concentration was 970 mumol/l, urea 34 mmol/l. Muscle biopsy corresponded to a subacute necrotizing myopathy with vacuole formation, signs typical of toxic damage. Renal biopsy confirmed advanced amyloidosis. The colchicine dose was reduced to 0.5 mg/d. The renal failure responded to conservative treatment. The myopathy symptoms receded within 4 weeks, creatinine clearance rising to 25 ml/min per 1.73 m2. 12 months after reduction of the colchicine dose the patient was without any FMF-related symptoms. PMID- 1499523 TI - [New aspects in the pathogenesis of gastroduodenal ulcer]. PMID- 1499524 TI - [Left ventricular diastolic function. I. The pathophysiology and diagnosis of diastolic dysfunction]. PMID- 1499525 TI - [The participation of the physician coworkers in the liquidation proceeds of the chief physician from an outpatient clinic. The judgement of the Federal Labor Court of 27 November 1991]. PMID- 1499526 TI - [Polymyalgia rheumatica and influenza vaccination]. PMID- 1499527 TI - [Myalgia after alcohol consumption]. PMID- 1499528 TI - [Physical interventions on the demand of the police--an injury to the medical duty of confidentiality?]. PMID- 1499529 TI - Videoendoscopic hysteroscopy: advanced technology in practice and research. PMID- 1499530 TI - Aspects of studies on the pathogenesis of equine laminitis. PMID- 1499532 TI - Clinical and radiographic features, treatment and outcome in 15 horses with fracture of the medial aspect of the patella. AB - A sagittal fracture of the medial aspect of the patella was identified in 15 horses, 2 of which had been kicked and 12 of which had hit a fixed fence while jumping. Eight horses showed concurrent fragmentation of the base of the patella, and 2 had sustained a concurrent fracture of the distal end of the lateral trochlear ridge of the femur. A cranioproximal-craniodistal oblique radiographic view was essential to identify the site of the medial patellar fracture and to determine its configuration. Fourteen horses were treated by surgical removal of the medial patellar fracture fragment(s). Of 12 horses (83%) without evidence of pre-existing degenerative joint disease, 10 were treated successfully with return to full athletic function. PMID- 1499531 TI - An association between complete and incomplete stress fractures of the humerus in racehorses. AB - Twenty-one horses had a complete unilateral humeral fracture during race training or racing at a California racetrack during the period 24 February 1990 to 10 July 1991. Fractures occurred approximately equally in left and right limbs, and in males and females. Most fractures occurred during training, and in 2- and 3-year old horses. Only 5 of 16 Thoroughbred horses with known racing records had previously raced more than once, and their mean time between races was less than the time between their last race and fracture (P = 0.07). Ten of 13 humeri studied further had gross evidence of periosteal callus bridging one portion of the fracture line, indicative of a pre-existing stress fracture. PMID- 1499533 TI - Microwave thermography: a non-invasive technique for investigation of injury of the superficial digital flexor tendon in the horse. AB - Microwave thermographs were recorded from 77 normal horses. In 51% the lowest temperature was recorded in the mid-metacarpal region, and in 41% it was in the distal metacarpal region. The mean temperature of the normal limbs ranged from 25.04 to 37.4 degrees C. Maximum temperature differences between symmetrical points in both forelimbs ranged from 0 to 5.33 degrees C and differences in mean limb temperatures between both forelimbs ranged from 0 to 2.91 degrees C. In 48 horses with acute (less than 4 weeks' duration) injury of the superficial digital flexor tendon (SDFT) (36 unilateral, 12 bilateral) and 12 horses with acute injury of the soft tissues of the palmar metacarpal region other than the SDFT (all unilateral) 66% of forelimbs had acute SDFT injury, and 50% of those with other soft tissue injuries, had elevations of the temperature in the mid- or distal metacarpal region. Abnormal values for mean limb temperature, difference in mean limb temperature and maximum temperature difference between locations in opposite forelimbs were detected in 75% of the horses with SDFT injury and in only 16% of the horses with other soft tissue injury. The sensitivity of microwave thermography for the detection of SDFT injury was 81% and the specificity 74%. When 30 horses in National Hunt training were examined weekly for 5 weeks, 2 horses sustained SDFT injury during that period. The microwave thermographs recorded from these 2 horses, at 1 and 2 weeks before the onset of clinical signs, were abnormal. However, 16 horses which did not develop tendon injury also displayed thermographic abnormalities. PMID- 1499534 TI - Videoendoscopic evaluation of the mare's uterus: I. Findings in normal fertile mares. AB - The new generation of videoendoscopes uses an electronic, instead of an optical, system for image transmission. Advantages over conventional fibre-optic endoscopes include increased image quality, handling robustness and direct display of the image on a TV monitor for multiple simultaneous viewing. In the present study, hysteroscopy was performed on 14 normal fertile Welsh Pony and Thoroughbred mares at various times during the annual and ovarian breeding cycles. Oestrus was characterised by an oedematous, relaxed cervix lying on the floor of the vagina, diffuse oedema of the endometrium and the occasional accumulation of small amounts of clear secretions in the uterine lumen. In dioestrus, the cervix appeared tight and pale and was located in the centre of the vaginal fornix. The endometrium appeared thinner due to the reduction in interstitial fluid, which allowed the underlying blood vessels to become visible, but it still had a glistening surface as a result of endometrial gland secretions. The appearance of the uterotubal papillae reflected the changes in the cervix, being relaxed, pinkish and oedematous during oestrus but remaining pale, tight and erect in dioestrus (between Days 7 and 12 after ovulation). A flexible polythene cannula was passed into the uterine lumen through the working channel of the endoscope for directed collection of uterine fluid for cytological and bacteriological examinations. Site-directed biopsies of the endometrium were taken, with flexible forceps inserted through the working channel of the endoscope, or with rigid forceps passed through the cervix alongside the endoscope. Both methods enabled accurate visual selection of the sampling area but the rigid forceps were preferred due to the larger size of the piece of endometrium recovered. PMID- 1499535 TI - Videoendoscopic evaluation of the mare's uterus: II. Findings in subfertile mares. AB - Videoendoscopy of the reproductive tract was performed in 87 Thoroughbred mares with histories of reduced fertility. During hysteroscopy samples for cytological, microbiological and histological examinations were obtained under visual control. Common findings in these broodmares included: (a) endometrial degeneration, as assessed by an uneven distribution or atrophy of endometrial folds and/or a scarred appearance of the endometrium (49 mares, 56%); (b) endometrial cysts of various sizes and locations within the uterus with the most common location being at the base of the uterine horns (48 mares, 55%); (c) fluid accumulation in the uterine lumen (28 mares, 32%). A few mares had transluminal adhesions (7 mares, 8%) and in 2 mares the adhesions appeared to obstruct one uterine horn completely. A solitary discrete lump was detected in the wall of the uterine body in one mare and the suspicion of it being a leiomyoma was confirmed histologically with the aid of a visually directed biopsy sample. Free intraluminal structures were present in the uterine lumen in 3 mares, including one inspissated blood clot and two suspected remnants of resorbing pregnancies. Flexible biopsy forceps and scissors passed through the working channel of the endoscope were used to sever small thin adhesions, but this method proved inadequate for multiple adhesions or cysts. Solitary endometrial cysts were removed by means of conventional rigid biopsy forceps passed alongside the endoscope, although bleeding from the operation site usually limited this type of intervention. PMID- 1499536 TI - Videoendoscopic evaluation of the mare's uterus: III. Findings in the pregnant mare. AB - During a 5-year period 65 Pony and 20 Thoroughbred pregnant mares were subjected to videoendoscopic hysteroscopy from 10 to 266 days of gestation. The aims of these examinations were to 1) observe foetal and placental development in vivo (60 Pony and 10 Thoroughbred mares); 2) eliminate one of unicornuate twin conceptuses (9 Thoroughbred mares); 3) recover embryonic foetal and placental tissues non-surgically for experimental purposes (47 Pony mares); 4) induce focal separation of the placenta in late gestation as an experimental model of placentitis (5 pony mares and 1 Thoroughbred mare). It was possible to view the embryo and all constituent extra-embryonic membranes of the conceptus between Days 10 and 87 of gestation without having to perforate the allantochorion. This allowed study of physiological processes such as the coordinated uterine contractions responsible for conceptus motility between Days 7 and 17, active foetal movements, which began as early as Day 34, and invasion of chorionic girdle cells into the endometrium, which occurred between Days 34 and 38. From Day 90, vision of the foetus was reduced or prevented by the increased thickness of the allantochorion. Transendoscopic recovery of the conceptus was successful in all of 10 mares under 30 days of gestation, whereas only 10 of 18 attempts between Days 30 and 45 produced the conceptus without resorting to uterine lavage after initial rupture of the allantochorion. All 9 attempts to eliminate one of unilateral twin conceptuses were unsuccessful and the technique was abandoned as clinically unsuitable. Nevertheless, 9 of 22 (41%) single conceptuses remained viable after one or more hysteroscopic examinations.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1499537 TI - Skeletal muscle characteristics in young trained and untrained standardbred trotters. AB - Muscle biopsies were taken from the middle gluteal muscle of 28 Standardbred trotters, 3-4 years of age. The 13 horses in Group T were trained consistently from 18 months of age, whereas the 15 horses in Group UT were not exposed to any systematic training before 3 years of age. Group T horses had a lower percentage of Type IIB fibres (31%) than did Group UT horses (39%). Citrate synthase (CS) activity, representing oxidative capacity, was higher in Group T (72 mmol kg-1 min-1) than in Group UT (47 mmol kg-1 min-1). Biopsies were taken from 4 horses in each group when they were foals and then annually until 3-4 years of age. Results from this study indicate that regular training of Standardbreds from 18 months of age resulted in increased CS activity and a decrease in the percentage of Type IIB fibres. This study shows that training, not growth, is the main factor that induces a high oxidative capacity and a high Type IIA/IIB fibre ratio in muscle of Standardbred trotters. PMID- 1499538 TI - Milk and water intakes of foals sucking grazing mares. AB - Intakes of milk and milk nutrients were determined for 8 foals at 11-18 days of age and for 10 foals at 30-44 days and 60-74 days of age while sucking grazing mares. Water intakes (sources other than milk) of the foals were determined at 30 44 days and 60-74 days of age. Five of the 10 mares were fed a protein supplement (24% crude protein) in addition to grazing during the stud season. The protein supplement did not influence foal intakes of milk and milk nutrients, milk composition, weight gains of the mares or the growth rate of the foals. Foal milk intakes increased (P less than 0.05) from 16.9 kg/day at 11-18 days to 18.1 kg/day at 60-74 days of age. The water intakes of the foals increased (P less than 0.01) from 3.9 kg/day at 30-44 days to 5.5 kg/day at 60-74 days of age. Total fluid intakes per kg foal liveweight were 246, 202 and 172 g at 11-18, 30 44 and 60-74 days of age, respectively. For each kg of weight gain, foals consumed 12.8, 15.7 and 16.4 kg milk at 11-18, 30-44 and 60-74 days of age. Stage of lactation had a significant effect on the total solids, lactose and protein content of milk. The fat and gross energy content of milk remained constant. PMID- 1499539 TI - Treatment of respiratory infections in horses with ceftiofur sodium. AB - Ceftiofur sodium was evaluated as a therapy for respiratory infections in horses. This cephalosporin antimicrobial was administered intramuscularly every 24 h and at a dose of 2.2 mg/kg (1.0 mg/lb) of body weight. The efficacy of ceftiofur sodium was compared with that of a positive control drug, ampicillin sodium (recommended dose of 6.6 mg/kg [3 mg/lb], given every 12 h). Both treatments were continued for 48 h after clinical symptoms were no longer evident (maximum of 10 days). Fifty-five (55) horses with naturally acquired respiratory infections were included in the study; 28 were treated with ceftiofur and 27 with ampicillin. Clinical improvement was recorded for 92.9% of the patients treated with ceftiofur and 92.6% of the animals receiving ampicillin. Both therapies reduced body temperatures to an afebrile level after 2 days of treatment. Complete recovery/cure was noted for 78.6% of the ceftiofur patients and 59.3% of the horses treated with ampicillin. Supporting variables (depression/malaise, respiration/dyspnoea, nasal discharge) were assessed and these also substantiated the effectiveness of the treatments. Both antibiotics were well tolerated. Neither pain nor swelling were noted at the ceftiofur injection site(s). None of the animals developed diarrhoea. Data from this study indicated that ceftiofur sodium is an effective and safe treatment for respiratory infections in horses. PMID- 1499540 TI - The incidence of abnormal limb development in the Irish thoroughbred from birth to 18 months. AB - A two part survey was carried out in Irish Thoroughbred horses in 1988 and 1989 to establish the incidence and prevalence of developmental skeletal problems, particularly possible manifestations of developmental orthopaedic disease (DOD). Survey One was a retrospective study based on a questionnaire involving the foal crops of 46 stud farms for 3 successive seasons; the 1711 animals initially documented represented 10.46% of Irish foal registrations. The second survey involved repeated monitoring of the 1988 foal crop from birth to 18 months of age on 17 stud farms. The 248 foals initially examined represented 4.24% of foal registrations. Treatment for DOD was deemed necessary for 11.3% of the animals in Survey One. Angular limb deformities and physeal dysplasia ("epiphysitis") together constituted 72.9% of the cases treated. The peak incidence of DOD problems occurred between weaning and the end of December. More than half the animals treated (53.9%) recovered completely, ie achieved expected sale value as yearlings, 27.5% of those treated showed incomplete recovery and mild to moderate loss of sale value and the remaining 18.7% were killed or lost much of their sale value. In the second survey, while 67% of animals exhibited some form of DOD, the incidence and severity of problems treated were not significantly different from those of farms in Survey One. Again, physeal dysplasia and angular limb deformity were the predominant clinical conditions and their severity was greatest during the early winter. During the suckling phase colts had a significantly greater incidence of DOD. At all other stages the incidence and severity of DOD was similar in both sexes.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1499541 TI - Radiographic anatomy of soft tissue attachments in the equine metacarpophalangeal and proximal phalangeal region. AB - The sites of bony attachment of the tendons, ligaments, and fibrous portion of the joint capsules of the equine metacarpophalangeal (fetlock) joint region were determined by gross dissection. These sites were transposed to standard radiographic views of the fetlock joint to yield illustrations that can be used as an aid in the diagnosis of soft tissue pathology from radiographs. Evidence of direct attachment of the common digital extensor tendon to the proximal phalanx was not found. Branches of the superficial digital flexor tendon were found to insert only on the middle phalanx. The recently described sites of insertion of the branches of the superficial digital flexor tendon to the proximal phalanx were found to be sites for attachment of the deep axial palmar ligaments of the proximal interphalangeal joint. PMID- 1499542 TI - Ultrasonographical and pathological studies of equine superficial digital flexor tendons; initial observations, including tissue characterisation by analysis of image grey scale, in a thoroughbred gelding. PMID- 1499543 TI - Histopathology in post-surgical laminitis with a peracute course in a horse. PMID- 1499544 TI - Bilateral infectious epididymitis in a stallion. PMID- 1499545 TI - Branchial cyst in a filly. PMID- 1499546 TI - Inhibition of calcium-dependent release of noradrenaline from PC12 cells by botulinum type-A neurotoxin. Long-term effects of the neurotoxin on intact cells. AB - (a) Clostridium botulinum type-A neurotoxin (BoNTA) inhibited the calcium dependent release of noradrenaline from PC12 cells in a dose-dependent manner. Under conditions in which intact PC12 cells were incubated with BoNTA for 20 h at 37 degrees C, a neurotoxin concentration of approximately 0.12 +/- 0.03 microM was required to inhibit 50% of the calcium-dependent noradrenaline release. (b) PC12 cells, differentiated in the presence of nerve growth factor for 14 days, showed a similar dose-dependent inhibition of noradrenaline release by BoNTA with unchanged sensitivity. No specific saturable binding of 125I-labelled BoNTA was observed to either differentiated or undifferentiated PC12 cells, suggesting a lack of high-affinity acceptors on the cell surface for the neurotoxin. It is proposed that BoNTA enters PC12 cells either by non-specific binding to the cell membrane or via a low-concentration low-affinity acceptor molecule. (c) A study of the long-term effects of BoNTA on noradrenaline release from PC12 cells showed that the neurotoxin remains active within the growing cells for several days. Noradrenaline release from PC12 cells exposed to BoNTA (0.3 microM) for 24 h was reduced to less than 20% of control values over a subsequent 4-day period. After 8 days, release levels were significantly lower (60-65%) than control values, despite a more than 10-fold increase in the cell mass. (d) Investigation of the subcellular distribution of BoNTA after incubation with PC12 cells for 96 h revealed the bulk of the toxin (94-98%) to be associated with the cell membrane fraction. Of this, 50-80% of the BoNTA was associated with the nuclear and cell debris fraction and 11-25% was recovered in the large-granule-vesicle fraction; the specific binding of the neurotoxin to these membrane fractions was found to be similar. (e) Examination of the form of the cell-associated BoNTA after incubation for 96 h with PC12 cells revealed no evidence of any significant degradation of either neurotoxin subunit. This suggests that the neurotoxin adopts a relatively stable form within the cell. On SDS/PAGE under non-reducing conditions, no trace of protein bands corresponding to either of the BoNTA subunits were observed, suggesting that little or none of the neurotoxin subunits exists in a monomeric form within the cells.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1499548 TI - Identification of the sites in the eukaryotic elongation factor 1 alpha involved in the binding of elongation factor 1 beta and aminoacyl-tRNA. AB - In this article we report the identification of the sites which are involved in the binding of the GDP-exchange factor EF-1 beta and aminoacyl tRNA to the alpha subunit of the eukaryotic elongation factor 1 (EF-1) from Artemia. For this purpose the polypeptide chain of EF-1 alpha, having 461 amino acid residues, was proteolytically cleaved into large fragments by distinct proteases. Under well defined conditions, a mixture of two large fragments, free from intact EF-1 alpha and with molecular masses of 37 kDa and 43 kDa, was obtained. The 37-kDa and 43 kDa fragments comprise the residues 129-461 and 69-461, respectively. However, in aqueous solution and under non-denaturing conditions, the mixture still contained a short amino-terminal peptide, encompassing the residues 1-36, that remained tightly bound. The ability of the mixture of the 37+43-kDa fragments, including this amino-terminal peptide 1-36, to bind GDP or to facilitate aminoacyl tRNA binding to salt-washed ribosomes was severely reduced, compared to intact EF-1 alpha. However, both of these complexes were able to bind to the GDP-exchange stimulating subunit EF-1 beta. A 30-kDa fragment, comprising the residues 1-287, was generated after treatment of the protein with endoproteinase Glu-C. This fragment contained the complete guanine nucleotide binding pocket. Although it was able to bind GDP and to transport aminoacyl tRNA to the ribosome, no affinity towards EF-1 beta was observed. We propose that the guanine-nucleotide-exchange stimulation by EF-1 beta is induced through binding of this factor to the carboxy terminal part of EF-1 alpha. As a result, a decreased susceptibility towards trypsin of the guanine-nucleotide-binding pocket of EF-1 alpha, especially in the region of its presumed effector loop is induced. PMID- 1499547 TI - Stimulation of a membrane tyrosine phosphatase activity by somatostatin analogues in rat pancreatic acinar cells. AB - A phosphoryl protein tyrosine phosphatase (PTPase) activity has been characterized in rat pancreatic acinar membranes using 32P-labeled poly(Glu,Tyr) as substrate. Acinar membranes exhibited a high affinity for the substrate, with an apparent Km of 0.46 microM and an apparent Vmax of 0.9 nmol.mg protein-1.min 1. Acinar membrane PTPase activity displayed specific characteristics of other PTPases; it was inhibited by the inhibitors Zn2+, orthovanadate and by the divalent cations Mn2+ and Mg2+, and was stimulated by the reducing-agent dithiothreitol. It was also inhibited by soybean trypsin inhibitor and stimulated by trypsin. Gel permeation of pancreatic acinar membranes gave a single peak of enzyme activity with an apparent molecular mass of 70 000 Da. Further purification by HPLC on DEAE revealed two peaks of PTPase activity at 120 mM and 180 mM NaCl. These two peaks reacted in a Western-blot procedure with anti (peptide) serum directed towards conserved domain of PTPase as a common 67-kDa form associated with lower-molecular-mass proteolytic fragments (31-56 kDa). Incubation of pancreatic acini with somatostatin analogues, SMS 201-995 or BIM 23014, resulted in a stimulation of membrane PTPase activity. The stimulation was rapid and transient, with a maximal level reached within 15 min of addition. The two analogs stimulated PTPase activity in a dose-dependent manner with half maximal activation occurring at 7 pM and 37 pM and maximal activation at 0.1 nM and 0.1-1 nM for SMS 201-995 and BIM 23014, respectively. The stimulated-membrane PTPase activity also eluted at an apparent molecular mass of 70 kDa in gel permeation chromatography. The two analogs inhibited the binding of [125I Tyr3]SMS 201-995 to pancreatic acinar membranes with similar relative potencies to that observed on stimulation of PTPase activity. We conclude that pancreatic acinar membranes possess a low-molecular-mass PTPase which is stimulated by somatostatin analogs at concentrations involving activation of membrane somatostatin receptors. PMID- 1499549 TI - Purification and characterization of a thermostable proteinase isolated from Thermus sp. strain Rt41A. AB - Thermus sp. strain Rt41A produces an extracellular thermostable alkaline proteinase. The enzyme has a high isoelectric point (10.25-10.5) which can be exploited in purification by using cation-exchange chromatography. The proteinase was purified to homogeneity and has a molecular mass of 32.5 kDa by SDS/PAGE. It is a glycoprotein, containing 0.7% carbohydrate as glucose equivalents, and has four half-cystine residues present as two disulphide bonds. Maximum proteolytic activity was observed at pH 8.0 against azocasein and greater than 75% of this activity was retained in the pH range 7.0-10.0. Substrate inhibition was observed with casein and azocasein. The enzyme was stable in the pH range 5.0-10.0 and maximum activity, in a 10-min assay, was observed at 90 degrees C with 5 mM CaCl2 present. No loss of activity was observed after 24 h at 70 degrees C and the half lives at 80 degrees C and 90 degrees C were 13.5 h and 20 min, respectively. Removal of Ca2+ reduced the temperature for maximum proteolytic activity against azocasein to 60 degrees C and the half-life at 70 degrees C was 2.85 min. The enzyme was stable at low and high ionic strength and in the presence of denaturing reagents and organic solvents. Rt41A proteinase cleaved a number of synthetic amino acid p-nitrophenol esters, the kinetic data indicating that small aliphatic or aromatic amino acids were the preferred residue at the P1 position. The kinetic data for the hydrolysis of a number of peptide p-nitroanilide substrates are also reported. Primary cleavage of the oxidized insulin B chain occurred at sites where the P1' amino acid was aromatic. Minor cleavage sites (24 h incubation) were for amino acids with aliphatic side chains at the P1' position. The esterase and insulin cleavage data indicate the specificity is similar for both the P1 and P1' sites. PMID- 1499550 TI - Ribonucleases of diverse specificities in rabbit brain nuclei. AB - A salt extract of rabbit brain nuclei contains three endoribonucleases, designated RNases Y, A and R, which produce acid-soluble products when incubated at near-neutral pH in the absence of metal ions. RNases Y and A yield products with the monoesterified phosphate at the 3' position, through 2',3' (cyclic)phosphate intermediates. Oligonucleotides terminating with a 2',3' (cyclic)phosphate are the end-products of the action of RNase R. Double-stranded substrates are highly resistant to the action of all enzymes. On the basis of limited hydrolysis of end-labelled 5S RNA, the three enzymes differ in their preference for the susceptible phosphodiester bond. Thus, RNase Y hydrolyses preferentially the YpN bond, RNase A the ApN bond and RNase R the RpU bond where R is guanosine in most cases. The advantages and disadvantages of using homopolyribonucleotides and dephosphorylated dinucleotides and trinucleotides in determining various aspects of the specificity of RNases are discussed. PMID- 1499551 TI - Glycosphingolipids in cestodes. Chemical structures of ceramide monosaccharide, disaccharide, trisaccharide and tetrasaccharide from metacestodes of the fox tapeworm, Taenia crassiceps (Cestoda: Cyclophyllidea). AB - The presence of glycosphingolipids in the metacestodes of the fox tapeworm, Taenia crassiceps, has been established. The normal-phase TLC pattern of the neutral-fraction glycolipids revealed groups of bands corresponding to homologous components of increasing sugar chain length. The three simplest glycolipid components have been isolated and their chemical constitution determined as being of the neogala series: Gal beta 1Cer, Gal beta 6Gal beta 1Cer and Gal beta 6Gal beta 6Gal beta 1Cer. The ceramide tetrasaccharide fraction has been found to consist of a mixture of neogalatetraosylceramide, as an elongation of the neogala series, Gal beta 6Gal beta 6Gal beta 6Gal beta 1Cer and the component Gal alpha 4Gal beta 6Gal beta 6Gal beta 1Cer (both occurring in approximately equimolar proportions). The long-chain bases of the ceramide monogalactoside, digalactoside, trigalactoside and tetragalactosides contain, as well as small amounts of sphingosine, predominantly dihydrosphingosine/phytosphingosine in the approximate ratios 1.7:1, 1.4:1, 1:1 and 2.3:1, respectively. The major ceramide fatty acids have particularly long chains, with hexacosanoic and octacosanoic acids predominating. Upon reverse-phase TCL, the glycolipid components ceramide monogalactoside, digalactoside and trigalactoside were each separable into five component bands. Parent glycolipid components therefore show component band distributions comparable to one another in being governed by similar ceramide constitutions. PMID- 1499552 TI - The structure of pneumococcal lipoteichoic acid. Improved preparation, chemical and mass spectrometric studies. AB - Pneumococcal lipoteichoic acid was extracted and purified by a novel, quick and effective procedure. Structural analysis included methylation, periodate oxidation, Smith degradation, oxidation with CrO3, and fast-atom-bombardment mass spectrometry. Hydrolysis with 48% (by mass) HF and subsequent phase partition yielded the lipid anchor (I), the dephosphorylated repeating unit of the chain (II) and a cleavage product of the latter (III). The proposed structures are: (I) Glc(beta 1----3)AATGal(beta 1----3)Glc(alpha 1----3)acyl2Gro, (II) Glc(beta 1--- 3)AATGal(alpha 1----4)GalNAc(alpha 1----3)GalNAc(beta 1----1)ribitol and (III) Glc(beta 1----3)AATGal(alpha 1----4)GalNAc(alpha 1----3)GalNAc, where AATGal is 2 acetamido-4-amino-2,4,6-trideoxygalactose, and all sugars are in the pyranose form and belong to the D-series. Alkaline phosphodiester cleavage of lipoteichoic acid, followed by treatment with phosphomonoesterase, resulted in the formation of II and IV, with IV as the prevailing species: [sequence: see text] The linkage between the repeating units was established as phosphodiester bond between ribitol 5-phosphate and position 6 of the glucosyl residue of adjacent units. The chain was shown to be linked to the lipid anchor by a phosphodiester between its ribitol 5-phosphate terminus and position 6 of the non-reducing glucosyl terminus of I. The lipoteichoic acid is polydisperse: the chain length may vary between 2 and 8 repeating units and variations were also observed for the fatty acid composition of the diacylglycerol moiety. Preliminary results suggest that repeating units II and IV are enriched in separate molecular species. All species were associated with Forssman antigenicity, albeit to a various extent when related to the non-phosphocholine phosphorus. Owing to its unique structure, the described macroamphiphile may be classified as atypical lipoteichoic acid. PMID- 1499553 TI - Sequence analysis of photoaffinity-labelled peptides derived by proteolysis of photosystem-2 reaction centres from thylakoid membranes treated with [14C]azidoatrazine. AB - Photosystem-2 reaction centres were prepared from pea thylakoid membranes that had been photoaffinity labelled with [14C]-azidoatrazine (2-azido-4-ethylamino-6 isopropylamino-s-triazine), a derivative of the herbicide atrazine which binds to the secondary plastoquinone electron-acceptor site of photosystem 2. SDS/PAGE of the 14C-labelled reaction centres followed by fluorography revealed photoaffinity labelled proteins of apparent molecular masses 30 kDa and 55 kDa, which corresponded to the D1 polypeptide and to an SDS-stable heterodimer of the D1 and D2 polypeptides, respectively. To obtain sequence information on the site of photoaffinity labelling, an 8-kDa photoaffinity-labelled peptide, generated by proteolysis of the reaction-centre material with trypsin, was isolated and purified to apparent homogeneity using reverse-phase and size-exclusion HPLC techniques. The amino terminus of the photoaffinity-labelled peptide was determined to be Leu-Gly-Met-Arg-Pro-Xaa-Ile-Ala-Val-Ala-Tyr by Edman sequencing. This corresponds to the amino terminus of a predicted tryptic peptide of D1 and confirms that azidoatrazine photolabels the D1 polypeptide of photosystem 2 in the region Leu137-Arg225. Chymotrypsin/trypsin digestion of photoaffinity labelled reaction centres followed by reverse-phase HPLC was used to isolate a smaller photoaffinity-labelled peptide. On Edman sequencing, Ser-Ala were identified as the first two residues and 14C was released on the third cycle, after which further degradation was blocked. The two potential peptide fragments with Ser-Ala at the amino terminus in the region Leu137-Arg225 are Ser148-Ala-Pro and Ser212-Ala-Met. Proline is an unlikely target for reaction with the nitrene of the photoactivated azidoatrazine, and the data are thus consistent with Met214 as the site of photoaffinity labelling on D1 when thylakoid membranes are illuminated with ultraviolet irradiation in the presence of [14C]azidoatrazine. PMID- 1499554 TI - Molecular cloning and characterization of the Saccharomyces cerevisiae CYT2 gene encoding cytochrome-c1-heme lyase. AB - Cytochrome c1, a subunit of the mitochondrial ubiquinol--cytochrome-c reductase, is synthesized on cytosolic ribosomes as a precursor protein of 37 kDa. Maturation to the mature 31-kDa form involves two proteolytic processing steps of the amino-terminal presequence. After removal of the amino-terminal part by the matrix-localized processing peptidase, the carboxy-terminal part of the presequence is cleaved off by an unknown intermembrane space protease. This step depends on covalent linkage of heme to the apoprotein. At least two complementation groups (I and II) can be distinguished among mutants of the yeast Saccharomyces cerevisiae, which are defective in this second proteolytic processing, i.e. they accumulate the intermediate-sized form of cytochrome c1 instead of the mature form. Recently, it was shown that complementation group II defines the structural gene for cytochrome c1 [Sadler, I., Suda, K., Schatz, G., Kaudewitz, F. & Haid, A., (1984) EMBO J. 3, 2137-2143]. We report on the molecular cloning and characterization of the CYT2 gene representing complementation group I. It maps on chromosome XI and encodes a mitochondrial protein of about 26 kDa. Extensive similarity to Neurospora crassa and S. cerevisiae cytochrome-c--heme lyase, as well as the phenotype of cyt2 mutants, strongly suggest that we have identified the gene for cytochrome-c1--heme lyase. PMID- 1499555 TI - Molecular characterization of a human anti-Rh(D) antibody with a DH segment encoded by a germ-line sequence. AB - The lambda-light-chain and lambda-heavy-chain variable-region genes of an anti Rh(D) (Rh, Rhesus; D, heavy-chain diversity region) human monoclonal antibody secreted by lymphocytes transformed by the Epstein-Barr virus have been cloned and sequenced. Sequence comparison of the anti-Rh(D)mAb lambda-chain variable region with those of the other available human lambda chains revealed that it belonged to the human V lambda I (V lambda, variable region of lambda chain) subgroup. The greatest sequence similarity (80%) was observed with that of another anti-Rh antibody lambda-chain directed against the Rh(c) antigen. For the VH (VH, variable region of heavy chain) sequence, the highest similarity (86%) was observed with the germline VHG3 gene which belongs to the VHI subgroup. The expressed DH sequence of the anti-Rh(D) antibody is also of germline origin and complementarity-determining region 3 is thus produced by VH-DH and DH-JH (J, joining region) joining without recombination of multiple DH gene segments. PMID- 1499556 TI - The effect of amino acid substitution at position 219 of Citrobacter freundii cephalosporinase on extension of its substrate spectrum. AB - The cephalosporinase of Citrobacter freundii GN346 is a class-C beta-lactamase comprising 361 amino acids. The substitution of the glutamic acid at position 219 in the enzyme by lysine was previously shown to broaden its substrate specificity to unfavorable substrates such as oxyimino cephalosporins [Tsukamoto, K., Ohno, R. & Sawai, T. (1990) J. Bacteriol. 172, 4348-4351]. To investigate the cause of this phenomenon, Glu219 was changed to glutamine, cysteine or tryptophan. All the resultant enzymes showed higher cefuroxime-hydrolytic activities than the wild type, the order of increasing cefuroxime-hydrolytic activity being as follows: Trp greater than Lys greater than Cys greater than Gln greater than Glu. The rate of hydrolysis of cefuroxime by the Trp219 enzyme was approximately 3 x 10(4) times that of the wild-type enzyme. The order of increasing cefuroxime hydrolysis was approximately proportional to the molecular volume of the amino acid substituted and independent of the ionic character of the amino acids. The cysteine residue at position 219 in the Cys219 enzyme allowed its complete reaction with an SH-blocking reagent, 4-chloromercuriphenylsulfonic acid. The modified enzyme with the bulkier residue showed a 45% higher cefuroxime hydrolytic activity than the untreated enzyme. These results suggested that extension of the substrate spectrum may be attributed to alteration in the configuration of the enzyme around position 219. PMID- 1499557 TI - Structural investigation on the lipopolysaccharide of Escherichia coli rough mutant F653 representing the R3 core type. PMID- 1499558 TI - Structural analysis of the N-linked carbohydrate chains of the 55-kDa glycoprotein family (PZP3) from porcine zona pellucida. PMID- 1499559 TI - The protein of M(r) 21,000 constituting the prosome-like particle of duck erythroblasts is homologous to apoferritin. AB - In duck erythroblasts, two major populations of untranslated messenger (m) RNP can be separated by sucrose gradient centrifugation in low ionic strength. One of these contains globin mRNA associated to protein factors, among them the prosomes. The other, sedimenting in the 35S zone, contains non-globin mRNA. From this '35S' mRNP, a new RNP particle called the prosome-like particle was isolated and characterized [Akhayat, O., Infante, A. A., Infante, D., Martins de Sa, C., Grossi de Sa, M.-F. & Scherrer, K. (1987) Eur. J. Biochem. 170, 23-33]. The PLP is a multimer of a protein of M(r) 21,000, and contains small RNA species. The particle is tightly associated with repressed mRNA and inhibits in vitro protein synthesis. We show here that the protein of M(r) 21,000, constituting the prosome like particle, is apoferritin. Different approaches confirm the RNP character of this particle and provide evidence that some of its RNA species are tRNA. The hypothesis is discussed as to whether (apo-)ferritin might serve other functions in addition to iron storage. PMID- 1499560 TI - The primary structure of the alpha subunit of a starfish guanosine-nucleotide binding regulatory protein involved in 1-methyladenine-induced oocyte maturation. AB - Starfish-oocyte maturation induced by 1-methyladenine (MeAde) was inhibited by microinjection of pertussis toxin (PTX). The inhibition appeared to result from PTX-catalyzed ADP-ribosylation of a 39-kDa guanosine-nucleotide-binding regulatory protein (G protein) in the oocyte. These results strongly support the hypothesis that the MeAde-induced signals operate via a membrane receptor and are carried by the PTX-sensitive G protein. When PTX-injected oocytes were treated with dithiothreitol, 85% of them reinitiated meiosis, suggesting that dithiothreitol did not act on the MeAde receptor. We constructed a cDNA library from the immature ovary of starfish, Asterina pectinifera, and screened it with the cDNA of the alpha subunit of an inhibitory rat G protein (Gi-2). A positive cDNA clone contained an open reading frame of 1062 bases which had 74% identity with the rat Gi-2 cDNA. The deduced amino acid sequence was 85% and 89% identical to rat Gi-2 and rat Gi-1, respectively. The alpha subunit of the G protein purified from cortices of starfish oocytes was digested by trypsin and the resulting four peptides were microsequenced. Comparison of these amino acid sequences with the predicted one indicated that the isolated cDNA clone encoded the alpha subunit of the PTX-sensitive G protein in oocytes. The C-terminal sequence, KNNLKDCGLF, was identical to that of Gi, suggesting that the cysteine residue is the site of ADP-ribosylation. PMID- 1499561 TI - Sequence of the tufA gene encoding elongation factor EF-Tu from Thermus aquaticus and overproduction of the protein in Escherichia coli. AB - The sequence of the tufA gene from the extreme thermophilic eubacterium Thermus aquaticus EP 00276 was determined. The GC content in third positions of codons is 89.5%, with an unusual predominance of guanosine (60.7%). The derived protein sequence differs from tufA- and tufB-encoded sequences for elongation factor Tu (EF-Tu) of Thermus thermophilus HB8, another member of the genus Thermus, in 10 of the 405 amino acid residues. Three exchanges are located in the additional loop of ten amino acids (182-191). The loop, probably involved in nucleotide binding, is absent in EF-Tu of the mesophile Escherichia coli. Since EF-Tu from E. coli is quite unstable, the protein is well-suited for analyzing molecular changes that lead to thermostabilization. Comparison of the EF-Tu domain I from E. coli and Thermus strains revealed clustered amino acid exchanges in the C terminal part of the first helix and in adjacent residues of the second loop inferred to interact with the ribosome. Most other exchanges in the guanine nucleotide binding domain are located in loops or nearest vicinity of loops suggesting their importance for thermostability. The T. aquaticus EF-Tu was overproduced in E. coli using the tac expression system. Identity of the recombinant T. aquaticus EF-Tu was verified by Western blot analysis, N-terminal sequencing and GDP binding assays. PMID- 1499562 TI - Biogenesis of the yeast vacuole (lysosome). Proteinase yscB contributes molecularly and kinetically to vacuolar hydrolase-precursor maturation. AB - The vacuolar proteinase yscB (PrB) has been implicated in the final maturation of procarboxypeptidase yscY (pro-CpY) to the mature wild-type form CpYb of 61 kDa. In PrB-deficient mutants, only the proteinase yscA processed form CpYa of 62 kDa is found [Mechler, B., Muller, H. & Wolf, D. H. (1987) EMBO J. 6, 2157-2163]. We report now that, akin to CpY, two forms of mature proteinase yscA (PrA) can be distinguished. In PrB-deficient mutant cells, PrAa, migrating at about 43 kDa in SDS/PAGE, is found, whereas PrAb, found in wild-type cells, had the known molecular mass of 42 kDa. In the PrB-deficient strain, pro-PrA and pro-CpY matured only to the higher-molecular-mass forms, PrAa and CpYa, and the maturation of both precursors was slower than in the isogenic wild-type strain. Pulse-labeling experiments indicated that the mature forms, PrAb or CpYb, are generated directly in the PrB-containing wild-type strain in vivo. In vitro experiments showed that PrB is able to trigger maturation of its 42-kDa pro-PrB precursor to mature PrB in the absence of PrA. Mature PrB and its proteolytic activity, however, shows a higher stability in the presence of mature PrA. The data indicate a molecular and kinetic participation of proteinase yscB in vacuolar hydrolase precursor maturation. PMID- 1499563 TI - Primary structures of ribosomal proteins L3 and L4 from Bacillus stearothermophilus. AB - Ribosomal proteins L3 and L4 were purified to homogeneity from total protein isolated from the 50S subunit of Bacillus stearothermophilus by reversed-phase high-performance liquid chromatography (RP-HPLC). Amino acid sequences of both proteins were determined by automated N-terminal sequence analysis and sequencing of internal peptides. Using oligonucleotides deduced from the N-terminal region of protein L3 as hybridization probes, a DNA fragment coding for proteins L3, L4 and the N-terminal part of protein L23 has been identified, cloned and sequenced. The organization of the genes is identical to that found in the S10 operon of Escherichia coli. Comparison of the sequences of proteins L3 and L4 with those of other organisms revealed that all proteins of the L3 family are highly conserved. On the other hand, the archaebacterial L4 proteins show no significant sequence similarity to the E. coli L4 protein whereas the L4 protein of B. stearothermophilus is significantly similar to all of the L4 proteins and thus justifies the membership of all the L4 proteins in one protein family. The results are discussed with respect to the phylogenetic relationship between eubacteria, archaebacteria and eukaryotes and possible functional domains of proteins L3 and L4. PMID- 1499564 TI - alpha 1(VIII)-collagen gene transcripts encode a short-chain collagen polypeptide and are expressed by various epithelial, endothelial and mesenchymal cells in newborn mouse tissues. AB - Type-VIII collagen is a major constituent of Descemet's membrane and contains two genetically distinct alpha chains, alpha 1(VIII) and alpha 2(VIII). We have previously cloned the human alpha 1(VIII) and alpha 2(VIII) genes and determined that they are located on chromosomes 3 and 1, respectively. Comparison of the alpha 1(VIII) and alpha 2(VIII) genes with the alpha 1(X)-collagen gene showed that the structure of the three genes and the sequence of their collagen polypeptides were strikingly similar. Therefore, we have grouped the three genes in a common subclass of collagens which we have named the short-chain collagens because of the relatively small size of their triple-helical domains. In the present study, we have isolated and characterized a mouse gene fragment encoding the entire mouse alpha 1(VIII)-collagen chain and determined the complete primary structure of the polypeptide chain. The size of mouse alpha 1(VIII)-collagen mRNA, as estimated by Northern-blot analysis, was 4.2 kb, compared with 2.8 kb previously reported for the corresponding rabbit mRNA. By cloning and sequencing of four overlapping cDNA, we demonstrate that this larger size of mouse alpha 1(VIII) mRNA is due to a larger 3' untranslated region in the mouse transcript. Using the gene fragment as a probe, we performed Northern-blot hybridization analysis of RNA prepared from newborn mice and demonstrated that alpha 1(VIII) collagen mRNA is expressed at high levels in the calvarium, eye and skin. In situ hybridization revealed that alpha 1(VIII) RNA is present in skin keratinocytes, corneal epithelial and endothelial cells, lens epithelial cells, as well as mesenchymal cells surrounding cartilage and calvarial bone and in the meninges surrounding the brain. PMID- 1499565 TI - Purification and characterization of a recombinant murine interleukin-6. Isolation of N- and C-terminally truncated forms. AB - Murine interleukin-6 (IL-6), when expressed in Escherichia coli using the pUC9 vector, accumulated as insoluble aggregates or 'inclusion bodies'. After selective urea washing of the inclusion bodies, to remove extraneous proteins, murine IL-6 was solubilized with 8 M guanidine hydrochloride and then rapidly purified to homogeneity by gel-permeation chromatography followed by reversed phase HPLC. It was demonstrated that complete disulfide bond formation in murine IL-6 occurred during the early urea washing/guanidine hydrochloride extraction steps, so no refolding step was required. When fully reduced murine IL-6 was dissolved in 8 M guanidine hydrochloride and allowed to air-oxidize, complete disulfide bond formation, monitored by analytical reversed-phase HPLC, was shown to occur within 13 h at 6 degrees C. About 25 mg pure protein was obtained from 37 g wet cells. This recombinant murine IL-6 had a specific activity in the hybridoma growth factor assay of 2 x 10(8) U/mg, which is equivalent to that of native murine IL-6. During the purification procedure, a number of variant forms of murine IL-6 were isolated and partially characterized. Two of these forms, T1 and T3, were C-terminal deletants of murine IL-6 lacking about 60 and 20 amino acids from the C-terminus, respectively, while the other form, T2, was an N terminal deletant lacking 37 amino acids from the N-terminus. None of these variant forms of murine IL-6 bound to the murine IL-6 receptor and, consequently, all were inactive in the hybridoma growth factor assay. PMID- 1499566 TI - Structural and functional characterisation of recombinant human haemoglobin A expressed in Saccharomyces cerevisiae. AB - Recombinant human HbA, produced by co-expressing alpha-globin and beta-globin chains in the yeast Saccharomyces cerevisiae, has been characterised extensively both physically and functionally. Structural studies using N-terminal sequence analysis, peptide mapping, amino acid composition analysis and electrospray MS demonstrated that the recombinant protein was identical to standard HbA purified from erythrocytes. The functional properties of the recombinant protein were assessed using equilibrium and kinetic measurements of oxygen and carbon monoxide binding. The oxygen-binding studies demonstrated that the yeast-derived HbA behaved as a fully functional, cooperative tetramer (Hill coefficient, 2.9), exhibited a normal Bohr effect and response to phosphate, and displayed a rate of oxygen dissociation identical to that of the native human molecule. The recombinant protein also showed the same characteristics of carbon monoxide combination as the standard protein. These studies demonstrate that yeast provides an ideal system for the production of Hb for structural and functional analysis and a potentially useful source of HbA for formulation into a Hb-based oxygen carrier. PMID- 1499567 TI - Urokinase binding to laminin-nidogen. Structural requirements and interactions with heparin. AB - Recently we have shown that heparin and related sulfated polyanions are low affinity ligands of the kringle domain in the amino-terminal region (ATF) of human urokinase (u-PA), and proposed that this may facilitate loading of u-PA onto its receptor at the focal contacts between adherent cells and their matrix. We have now tested other components of the cell matrix (fibronectin, vitronectin, thrombospondin and laminin-nidogen) for u-PA binding, and found that laminin nidogen is also a ligand of the u-PA ATF. Direct binding assays and competition binding assays with defined fragments of laminin-nidogen showed that there are u PA binding sites in fragment E4 of laminin as well as in nidogen. The long-arm terminal domain of laminin (fragment E3), which contains a heparin-binding site, competed for binding of u-PA to immobilised heparin. However nidogen, which does not bind to heparin, also inhibited binding of u-PA to heparin, and this effect was also observed with recombinant nidogen and with a fragment of nidogen lacking the carboxy-terminal domain. Direct binding assays confirmed that u-PA binds to nidogen through a site in the u-PA ATF. We conclude that u-PA binds to laminin nidogen by interactions involving the ATF region of u-PA, the E4 domain of laminin and the rod or amino-terminal regions of nidogen. Since nidogen is suggested to be an important bridging molecule in the maintenance of the supramolecular organization in basement membranes, the presence of a binding site for u-PA in nidogen indicates a role for plasminogen activation in basement membrane remodelling. PMID- 1499568 TI - Penicillin-binding protein 2x of Streptococcus pneumoniae. Expression in Escherichia coli and purification of a soluble enzymatically active derivative. AB - A 2.5-kb DNA fragment including the structural gene coding for the penicillin binding protein 2x (PBP 2x) of Streptococcus pneumoniae has been cloned into the vector pJDC9 and expressed in Escherichia coli. Mapping of RNA polymerase binding sites by electron microscopy indicated that the pbpX promoter is well recognized by the E. coli enzyme. However, high-level expression occurred mainly under the control of the lac promoter upstream of the pJDC9 multiple cloning site. After induction with isopropyl beta-d-thiogalactopyranoside, PBP 2x was expressed as one of the major cellular proteins. PBP 2x produced in E. coli corresponded to the pneumococcal PBP 2x in terms of electrophoretic mobility, fractionation with the cytoplasmic membrane, and penicillin-binding capacity. Deletion of 30 hydrophobic N-terminal amino acid residues at positions 19-48 resulted in high level expression of a cytoplasmic, soluble PBP 2x derivative (PBP 2x*) which still retained full beta-lactam-binding activity. A two-step procedure involving dye affinity chromatography was established for obtaining large amounts of highly purified enzymatically active PBP 2x*. PMID- 1499569 TI - Regulation of the mammalian carbamoyl-phosphate synthetase II by effectors and phosphorylation. Altered affinity for ATP and magnesium ions measured using the ammonia-dependent part reaction. AB - We have measured the 'core' mammalian carbamoyl-phosphate synthetase II (CPSII) activity, using NH4Cl as the nitrogen-donating substrate and trapping carbamoyl phosphate as urea through its reaction with ammonium ions. When ATP and magnesium ion concentrations are close to those found in the cell, the substrate saturation curves for ammonia and bicarbonate are hyperbolic, giving Km (NH3) values of 166 microM at high ATP concentrations and 26 microM at low ATP concentrations, while the Km (bicarbonate) is 1.4 mM at both ATP concentrations used. These values for the Km (NH3) are lower than previously reported for CPS II, and closer to the values for the mitochondrial counterpart. The Km for ammonia and bicarbonate are not altered by phosphorylation of the multienzyme polypeptide CAD, which contains the first three enzyme activities of pyrimidine biosynthesis. The CPS II activity is lower with an excess of either ATP or magnesium ions, causing the apparently sigmoid dependence of activity upon ATP concentration to be enhanced at low concentrations of free magnesium ions. The feedback inhibitor, UTP, acts by stabilising a state with a low affinity for magnesium ions and for ATP. In the presence of the activator, 5-phosphoribosyl diphosphate (PRibPP), the enzyme has a higher affinity for magnesium ions and thus the ATP dependence of the activity is hyperbolic. Phosphorylation of CAD similarly activates the CPS II enzyme by increasing the affinity for magnesium ions and by pushing the equilibrium away from the low-affinity UTP-stabilised state. Using our improved assay procedure, we observe a very large activation by PRibPP of carbamoylphosphate synthesis at low concentrations of magnesium ions, and we find that unlike UTP, the activator PRibPP is able to act on the phosphorylated enzyme. PMID- 1499570 TI - Biosynthesis of vitamin B12. Transformation of riboflavin 2H-labeled in the 1'R position of 1'S position into 5,6-dimethylbenzimidazole. AB - The 5,6-dimethylbenzimidazole moiety of vitamin B12 is formed from riboflavin in aerobic and some aerotolerant bacteria. Thereby C1' of riboflavin is transformed into C2 of the vitamin B12 base. In the present publication a study on this transformation with riboflavin 2H-labeled in the 1'R or 1'S position is described. This study was undertaken in order to find out if one of the two hydrogens at C1' is transferred to C2 of 5,6-dimethylbenzimidazole. The 2H labeled riboflavin samples were synthesized starting from unlabeled or 1-2H labeled ribose and 3,4-dimethylaniline yielding N-beta-D-ribopyranosyl-3,4 dimethylaniline. The unlabeled riboside was reduced to N-D-ribityl-3,4 dimethylaniline with sodium cyanoborotrideuteride, the 2H-labeled riboside with sodium cyanoborohydride. The ribityl derivatives were transformed into N-D ribityl-2-phenylazo-4,5-dimethylaniline, and condensed with barbituric acid to riboflavin. The reduction of the ribosyl compound to the ribityl derivative is only partially stereospecific. Thus the riboflavin synthesized from unlabeled ribose had a 2H ratio of 3/1 (1'R/1'S), the riboflavin obtained from D-[1 2H1]ribose of 1/3 (1'R/1'S). The 2H content in these positions was determined from the 1H-NMR spectra. These spectra showed also that 1 mol 2H/mol riboflavin was present in position 1'. The deuterated riboflavin samples were incubated under aerobic conditions with broken cell preparations of Propionibacterium shermanii. The deuterium content of the 5,6-dimethylbenzimidazole isolated was determined by mass spectrometry and by 1H NMR. These measurements revealed that the hydrogen in the pro-S position at C1' of riboflavin is retained during 5,6 dimethylbenzimidazole formation, and is thus found at C2 of this base. PMID- 1499571 TI - Distinct N-glycan fucosylation potentials of three lepidopteran cell lines. AB - The fucosyltransferase activities of three insect cell lines, MB-0503 (from Mamestra brassicae), BM-N (from Bombyx mori) and Sf-9 (from Spodoptera frugiperda), were investigated and compared with that of honeybee venom glands. Cell extracts and venom gland extracts were incubated with GDP-[14C]fucose and glycopeptides isolated from human IgG and from bovine fibrin. The labeled oligosaccharide products were released by peptide-N4-(N-acetyl-beta glucosaminyl)asparagine amidase A, fluorescence marked with 2-aminopyridine and analyzed both by reversed-phase and size-fractionation HPLC. They were identified by their elution positions before and after exoglycosidase treatment in comparison with standard oligosaccharides. These experiments revealed distinct fucosylation potentials in the three cell lines tested. While MB-0503 cells, like honeybee venom glands, are able to transfer fucose into alpha 1-3 and alpha 1-6 linkage to the innermost N-acetylglucosamine, only alpha 1-6-fucosyl linkages were detected with BM-N and Sf-9 cells. PMID- 1499572 TI - Primary structure of neutral and acidic oligosaccharide-alditols derived from the jelly coat of the Mexican axolotl. Occurrence of oligosaccharides with fucosyl(alpha 1-3)fucosyl(alpha 1-4)-3-deoxy-D-glycero-D-galacto-nonulosonic acid and galactosyl(alpha 1-4)[fucosyl(alpha 1-2)]galactosyl(beta 1-4)-N acetylglucosamine sequences. AB - Six major neutral and acidic oligosaccharide-alditols were prepared from the jelly coat of Mexican axolotl eggs. These compounds were demonstrated to contain 3-deoxy-D-glycero-D-galacto-nonulosonic acid (dNloA) and L-fucose (Fuc). The structures of the six major oligosaccharides were established as follows: [sequence: see text] PMID- 1499574 TI - Transient cardiac constriction following purulent pericarditis. AB - Transient cardiac constriction is an unusual complication of purulent pericarditis. It should be suspected in the presence of clinical and haemodynamic deterioration when signs of activity have abated. Features of cardiac constriction were observed in a 4-year-old boy 2 weeks after surgical drainage. The patient was managed conservatively without surgery and the outcome was good. Follow up 2 years later showed a healthy boy with a normal cardiological examination. PMID- 1499573 TI - Molecular hybridization techniques in current diagnosis of chronic hepatitis B in childhood. AB - Following the cloning and sequencing of the hepatitis B virus genome, molecular hybridization techniques have been established to detect hepatitis B virus (HBV) DNA in serum and liver tissue. Analyses can be performed by dot blot, Southern blot and in situ hybridization. HBV DNA is regarded to be the most sensitive marker of viral replication and infectivity which was previously related to the presence of hepatitis B e antigen in serum and hepatitis B core antigen in liver cells. In liver tissue different molecular patterns can be recognized as free viral DNA and integrated sequences. Furthermore, introduction of the polymerase chain reaction allows the detection of very small amounts of viral DNA and has markedly improved diagnostic sensitivity. Thus the study of HBV DNA has become a valuable part of the routine diagnosis in chronic hepatitis B, providing a more reliable evaluation of virus replication and infectivity, and facilitating more precise statements about course and prognosis of the disease. PMID- 1499575 TI - Lethal junctional epidermolysis bullosa with normal expression of BM 600 and antro-pyloric atresia: a new variant of junctional epidermolysis bullosa? AB - A newborn girl is described with a lethal junctional epidermolysis bullosa (Herlitz form) (JEB) associated with a congenital localized absence of skin, and a pyloric atresia (PA). The post-mortem examination of the digestive tract showed a widespread cleavage between the epithelium and the chorion. Immunohistological and electron microscopical examination showed a cleavage occurring through the lamina lucida of the digestive basement membrane, as for the skin blisters. Despite the lethal character of this form of JEB, the BM 600 glycoprotein was normally recognized at the dermo-epidermal junction by the monoclonal antibody GB3. This rare association of lethal JEB-PA-localized absence of skin, with a quite unusual GB3 positive immunophenotype could correspond to a new variant of JEB. PMID- 1499576 TI - Development of height and weight in children with diabetes mellitus: report on two prospective multicentre studies, one cross-sectional, one longitudinal. AB - Optimal regimen for insulin therapy should lead to normal longitudinal growth and weight gain in children with diabetes mellitus. However, reports published so far indicate that this goal of paediatric diabetology is currently not achieved in a considerable number of patients. In a cross-sectional sample of 89 children with insulin dependent diabetes mellitus (IDDM) for more than 3 years, we found the relation of height to weight to be significantly different compared to 102 healthy school children of similar age. Using bivariate analysis, body shape in these children with diabetes was shifted towards small and obese (P less than 0.05) compared to control children. We subsequently initiated a longitudinal study and followed children from the onset of diabetes for the following 3 years, recording height, weight and bone age as well as glycosylated haemoglobin and daily insulin requirement. At diagnosis, height SDS was identical in children with IDDM (+0.04 +/- 0.10) compared to control children (-0.07 +/- 0.10; M +/- SE), while weight SDS was -0.26 +/- 0.10 in children with diabetes (controls: + 0.01 +/- 0.01). Bone age was identically retarded in newly diagnosed IDDM children (-0.73 +/- 0.12 SDS) and in our control group of children from the same regional background (-0.50 +/- 0.12; n.s.). In this group of children with diabetes mellitus followed prospectively, height to weight relationship differed from controls after 2 and after 3 years of the disease (P less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1499577 TI - Diagnostic value of growth hormone-releasing hormone test in children and adolescents with idiopathic growth hormone deficiency. AB - Average growth hormone (GH) peaks following an i.v. growth hormone releasing hormone (GHRH) 1-29 stimulation test were significantly lower in 48 children and adolescents with GH deficiency (GHD) than in 20 age-matched controls (15.2 + 12.7 vs 37.5 + 28.1 ng/ml, 2 P less than 0.001). Twelve patients exhibited a low GH peak (less than 5 ng/ml), 27 demonstrated a normal response (greater than 10 ng/ml) and 9 showed an intermediate rise in plasma GH (5-10 ng/ml). Six of the 12 patients with low GH response to the first GHRH stimulation failed to respond to two other tests immediately before and after a 1 week priming with s.c. GHRH. These subjects with subnormal GH increase at repeat testing had total GHD (TGHD) and multiple pituitary hormone deficiency (MPHD) and had suffered from perinatal distress. On the contrary, 26 of 27 patients with normal GH response to the first test had isolated GHD and only a minority (8/27) had signs of perinatal distress. It is concluded that perinatal injuries primarily damage pituitary structures and that a pituitary defect more probably underlies more severe forms (TGHD and MPHD) of GHD. PMID- 1499578 TI - The association of hypopituitarism with small pituitary, invisible pituitary stalk, type 1 Arnold-Chiari malformation, and syringomyelia in seven patients born in breech position: a further proof of birth injury theory on the pathogenesis of "idiopathic hypopituitarism". AB - We report seven cases of hypopituitarism all having a history of breech delivery, asphyxia at birth, and syringomyelia. A small pituitary gland was found on MRI or CT in six cases, invisible pituitary stalk on MRI in five cases, and type 1 Arnold-Chiari malformation in six cases. A constellation of these abnormalities are best explained by traction of brain and spinal cord of the subjects exerted during breech delivery and further support the primary role of birth trauma in the genesis of "idiopathic hypopituitarism". PMID- 1499579 TI - Iatrogenic IgG2 deficiency in a leukaemic child. A case report. AB - A girl with acute non-lymphoblastic leukaemia was treated with immunosuppressive chemotherapy. After cessation of therapy she had three consecutive episodes of infection due to Streptococcus pneumoniae from which she recovered and was shown to have developed a combined deficiency of both IgG2 and IgG4. The patient eventually relapsed and died 3 years after the initial diagnosis. The importance of measuring IgG subclasses in patients treated with immunosuppressive chemotherapy is discussed. PMID- 1499580 TI - IgG subclass deficiency in children with recurrent bronchitis. AB - We studied the incidence of IgG subclass deficiency in children with recurrent bronchitis. Recurrent bronchitis was defined as three or more episodes a year during at least 2 consecutive years, of bronchopulmonary infection, productive cough with or without fever and/or diffuse rales by physical examination in the absence of asthma or atopy. Fifty three children were selected, of whom 30 (57%) were deficient in one of the IgG subclasses. None had an IgG1 deficiency. Nine (17%) were deficient in IgG2, 9 (17%) in IgG3 and 20 (38%) in IgG4. Isolated IgG subclass deficiencies were most frequently seen for IgG4 (14, 26%), less for IgG3 (6, 12%) and even less for IgG2 (4, 7%). Nine (17%) children were IgA deficient and 8 (15%) IgG deficient with a combined IgG subclass deficiency in 8 and 7 of them respectively. By subdivision into different age groups most patients were encountered in the youngest group. The mean content of IgG2, IgG3 and IgG4 in 3- to 4-year-old children with recurrent bronchitis was significantly lower than in the age matched controls. The mean value for IgG4 in the 5- to 6-year-olds was significantly lower than in the control group. This study demonstrates the correlation between recurrent bronchitis in childhood and IgG subclass deficiency. IgG subclass deficiency and recurrent bronchitis are both quite prominent phenomena in young children but rare in older children, suggesting a transient immaturity of the immune system as one of the possible pathogenetic factors. An IgA or an IgG deficiency is highly suggestive for the existence of a combined IgG subclass deficiency. PMID- 1499581 TI - Spontaneous growth in Turner syndrome: evidence for a minor pubertal growth spurt. AB - Spontaneous growth of 141 untreated girls with Turner syndrome was analysed. Of the patients 25% were born prematurely; their weight and height were normal when compared to prematurely born healthy infants. However, birth weight and height was significantly retarded in Turner patients born at term. A curve for height and growth velocity for the age range 0-16 years was constructed with a sensitive statistical method. By use of a mathematical model equations were created for calculating z-scores and the related percentiles for the height of individual patients at given age. Median height of 18 untreated patients at 18 years was 143.8 cm. Analysis of growth velocity revealed a minor but significant growth spurt at the age of 12.5 years. This growth spurt was also detectable in patients without signs of spontaneous puberty and occurred later in patients with 45,X0 karyotype. Bone age progression was linear up to the age of 7.5 years and decelerated thereafter. PMID- 1499582 TI - A family with one child with acrocallosal syndrome, one child with anencephaly polydactyly, and parental consanguinity. AB - A 2-year-old boy with typical features of the acrocallosal syndrome is presented. His parents are first degree cousins and their first pregnancy resulted in spontaneous abortion whereas the offspring of their second pregnancy was an anencephalic baby with bilateral post-axial polydactyly of the hands. The possibility of including anencephaly in the spectrum of the CNS malformations of the acrocallosal syndrome is suggested. PMID- 1499583 TI - The relationship of fluid restriction during the 1st month of life to the occurrence and severity of bronchopulmonary dysplasia in low birth weight infants: a 1-year radiological follow up. AB - One hundred consecutive low birth weight (LBW) infants (less than 1751 g) were randomized into a study group having a restricted fluid intake until 4 weeks of age and a control group following the fluid regimen conventionally used in the hospital. Chest X-ray films were examined on admission, at the ages of 3 days, 7 days, 2 weeks and 4 weeks and at bi-monthly visits to the out-patient clinic up to 1 year of age or until the chest examinations were normal. The severity of hyaline membrane disease (HMD) and typical radiological abnormalities of bronchopulmonary dysplasia (BPD) were assessed. Twelve patients succumbed, 1 in the study group and 11 in the control group. The study group seemed to experience less severe HMD than the controls. Of the former 54% and 32% of the latter were alive and had no radiographical signs of BPD at 4 weeks of age (P less than 0.05). The difference between the groups in the cumulative number of normal chest X-ray examinations during the follow up was even more significant. The percentage of normal X-ray films at 1 year of age was 92% in the study group and 72% in the control group. These results suggest that fluid restriction for the first 4 weeks of life can lower the incidence of radiological abnormalities typical of BPD obtained during the 1st year of life in LBW infants. Pulmonary oedema seems to be a significant aetiological factor causing HMD to develop into chronic lung disease. PMID- 1499584 TI - Neonatal intestinal perforation due to congenital defects in the intestinal muscularis. AB - Congenital defect of the muscular layer of the small intestine is a rare cause of spontaneous bowel perforation in premature infants. During the last 12 years we have observed four similar cases. We describe the most recent one, a premature infant who developed two abdominal events. On her 2nd day of life, spontaneous perforation of the distal ileum due to focal absence of the muscular layer occurred. Several weeks later she developed the typical clinical and histological picture of necrotizing enterocolitis. The clinical and histological characteristics of the two different conditions are compared, and the 24 cases reported in the literature are discussed. We conclude that focal absence of intestinal musculature may be not such a rare entity as is commonly believed. PMID- 1499586 TI - Asymptomatic urinary tract infection in childhood. AB - In this study 2,591 apparently healthy children aged 1 day-16 years were examined to determine the existence of asymptomatic urinary tract infection. A prevalence of 4% in newborns, 5.2% in infants, 5.8% in preschool children, 4.5% in elementary school children, and of 4.8% in high-school children was found. PMID- 1499585 TI - Intra-uterine long bone growth in small-for-gestational-age infants. AB - To better understand the intra-uterine bone modelling and remodelling process in small-for-gestational-age (SGA) newborn infants, long bone growth was studied using postmortem X-ray films in a group of such infants (n = 34). Bone length, diaphyseal diameter, medullary diameter, cortical thickness, cortical area, the Barnett-Nordin index, and the percentage of cortical area were determined in femur, tibia, and humerus. A separate group of appropriate-for-gestational-age (AGA) newborn infants (n = 146) was used as controls. Length and cortical bone mass in all three bones were significantly lower in SGA infants than in AGA infants. Decreased cortical bone mass in SGA infants was the result of decreased diaphyseal diameters and increased medullary diameters. Similar results were obtained when SGA infants were subclassified as preterm and term and compared with the control group of AGA infants. Bone lengths and diaphyseal diameters in SGA infants did not differ from those observed in a weight-matched control group of AGA infants although the latter were younger by 4 weeks' gestation. However, the cortical bone mass was lower than in the control group because of the relative greater medullary diameters in all three long bones in the SGA infants. Our present results indicate that reduced cortical bone mass in SGA infants is a mixed growth modelling and remodelling dependent process. PMID- 1499587 TI - Plasma exchange for fulminant Wilson disease. PMID- 1499588 TI - Beta-mannosidosis and ethanolaminuria in a female patient. PMID- 1499589 TI - Branchio-oculo-facial syndrome. Report of a new case with agenesis of cerebellar vermis. PMID- 1499590 TI - Haemorrhagic cystitis and urinary retention in Henoch-Schonlein purpura. PMID- 1499591 TI - 3-Methylglutaconic aciduria in a patient with a disturbed mitochondrial energy metabolism. PMID- 1499592 TI - Urinary N-acetyl-beta-D-glucosaminidase activity in a girl with distal renal tubular acidosis. PMID- 1499593 TI - Identification of detomidine carboxylic acid as the major urinary metabolite of detomidine in the horse. AB - Horse urine was investigated for metabolites by chromatography and mass spectrometry following the oral administration of the large animal analgesic sedative detomidine to two stallions and intravenous administration of [3H] detomidine to a mare. Detomidine carboxylic acid and hydroxydetomidine glucuronic acid conjugate were identified in the urine after the oral doses. In addition, traces of free hydroxydetomidine were observed. About half of the radioactivity of [3H]-detomidine was excreted in the urine in 12 h after the i.v. dose (80 micrograms/kg). Most of the excretion occurred between 5 and 12 h in contrast to urine output which was highest 2-5 h after the dosing. The major radioactive metabolite in the urine was detomidine carboxylic acid. It comprised more than two thirds of the total metabolites in all the urine fractions collected. Its excretion profile was similar to that of total radioactivity. Hydroxydetomidine glucuronide was also excreted. It contributed 10-20% of the total metabolites in the urine. The free aglycone was only seen in the samples collected during the peak urine flow. A minor metabolite was tentatively characterized as the glucuronide of N-hydroxydetomidine. PMID- 1499594 TI - Metabolic disposition of the non-steroidal anti-inflammatory agent isoxicam in man. AB - The metabolic fate of isoxicam, a long half-life non-steroidal anti-inflammatory agent, in human subjects was investigated using isoxicam labelled with 14C in the N-methyl position. Three healthy male subjects were each administered a single oral 200 mg dose (90.7 microCi) with plasma and urine collected. Total plasma radioactivity peaked between 8 and 24 h postdose with mean 14C plasma radioactivity half-life of 36.1 h. Low levels of plasma radioactivity precluded plasma metabolic profiling. In urine, 37% of the administered radioactivity was recovered through 168 h. Metabolic profiling of urine confirmed the major oxidative excretion product as the hydroxymethylisoxazole metabolite. Identified and confirmed as minor urinary metabolites were radiolabelled open-ring sulfonamide and N-methylsaccharin. Non-labelled saccharin formed by oxidative loss of the 14C N-methyl group from N-methylsaccharin, was also observed. The role of this 'saccharin pathway' in the overall human disposition of isoxicam remains to be elucidated. PMID- 1499595 TI - Clinical pharmacokinetics of the nifedipine/co-dergocrine combination in impaired liver and renal function. AB - Following a single oral dose of 20 mg nifedipine combined with 2 mg co-dergocrine to 24 subjects, the pharmacokinetics of this drug were studied. 8 normotensive subjects had normal renal and hepatic function, 8 patients had chronic renal insufficiency (creatinine clearance less than 30 ml.min-1) and 8 patients had liver cirrhosis which was confirmed by liver biopsy. The area under the plasma level time curve (AUC infinity) of co-dergocrine increased from 0.59 +/- 0.41 ng.ml-1. (mean +/- SD) in the normals to 1.24 +/- 0.95 ng.ml-1.h in liver cirrhosis (P less than 0.05) and to 1.81 +/- 0.9 ng.ml-1.h in renal failure (P less than 0.05 compared with the control group). Corresponding values for the nifedipine AUC infinity were 564.5 +/- 268 ng.ml-1.h, 1547.5 +/- 1134 (P less than 0.05) and 929 +/- 533 ng.ml-1.h (P less than 0.05; gas chromatographic method). The incidence of adverse effects was lower in patients with renal failure than in subjects with normal renal and liver function as well as in those with liver cirrhosis. PMID- 1499596 TI - Comparative bioavailability of Silipide, a new flavanolignan complex, in rats. AB - The comparative pharmacokinetics of Silipide (IdB 1016, a silybin phosphatidylcholine complex) and silybin were investigated by measuring unconjugated and total plasma silybin levels as well as total biliary and urinary silybin excretion in rats following administration of a single oral dose (200 mg/kg as silybin). Mean peak levels of unconjugated and total silybin after IdB 1016 were 8.17 and 74.23 micrograms/ml respectively. Mean AUC (0-6 h) values were 9.78 and 232.15 h.micrograms.ml-1 indicating that about 94% of the plasma silybin is present in a conjugated form. After administration of silybin, plasma levels of both unconjugated and total compound were under the analytical detection limit. Cumulative biliary (0-24 h) and urinary (0-72 h) excretion values after administration of IdB 1016 accounted for 3.73% and 3.26% of the administered dose, respectively. After silybin administration, the biliary and urinary excretion accounted for only 0.001% and 0.032% of the dose respectively. Our results indicate a superior bioavailability of silybin administered orally as IdB 1016. This was due mainly to an impressive increase in gastrointestinal absorption. PMID- 1499597 TI - Metabolism of diazepam and related benzodiazepines by human liver microsomes. AB - The metabolism of diazepam has been studied in vitro using microsomal preparations from five human livers. An HPLC method was developed for the assay of diazepam, its congeners and its metabolites. Various methods for the incorporation of diazepam into the incubation medium were explored. It was shown that the use of organic solvents or small quantities of hydrochloric acid enhanced the solubility of this substrate. However all of the organic solvents tested were associated with substantial (around 50%) inhibition of metabolism of diazepam by both major pathways (N-demethylation and C3-hydroxylation). The use of hydrochloric acid gave satisfactory solubilization of diazepam, but not of pinazepam, prazepam or halazepam. Detailed metabolic studies were conducted only for diazepam, using neither hydrochloric acid nor organic solvents in the incubation medium. Formation of N-desmethyl-diazepam increased approximately linearly with diazepam concentration to 200 microM, and did not show saturation. Formation of temazepam gave a curved profile over the same range of diazepam concentrations, suggestive of a sigmoidal relationship. Michaelis-Menten parameters could not be determined for either reaction, but intrinsic clearances for N-demethylation varied over a 6-fold range. Diazepam N-demethylation was apparently promoted by the inclusion of temazepam in the incubation medium, while C3-hydroxylation of diazepam was enhanced in the presence of N-desmethyldiazepam. Mephenytoin in the incubation mixture had no effect on diazepam metabolism by either pathway. The present studies have defined some of the methodological problems inherent in in vitro metabolic studies with benzodiazepines, and have shed further light on the metabolism of diazepam in vitro by human liver. PMID- 1499598 TI - Influence of food on the oral bioavailability of moxonidine. AB - Moxonidine is a new centrally acting anti-hypertensive with a very low adverse drug reaction profile. Among others, the aim of the study presented here was to determine the influence of food on the pharmacokinetics of moxonidine. Single oral moxonidine doses of 0.2 mg fasting and 0.2 mg non-fasting were administered in a randomized cross-over study. Eighteen subjects participated in the study, all of whom completed the study according to the protocol. Three sets of analytical plasma data could not be evaluated pharmacokinetically giving a total number of 15 evaluable cases. Renal excretion was evaluated for all 18 subjects. Food intake had no influence on the pharmacokinetics of moxonidine. The relative bioavailability of moxonidine administered under non-fasting conditions reached 94% of the bioavailability after fasted administration. Food intake resulted in a slight decrease of Cmax and a minimal increase of tmax as compared to the fasted treatment. The absorption half-life t1/2a showed a minor prolongation. These differences were not statistically significant in any of the parameters. For t1/2 lambda 2, CLtot and Ae(24h) no statistically significant differences were found between the fasting and non-fasting treatment. The amount of moxonidine excreted unchanged in urine accounted for about 46% of the dose administered after both treatments. PMID- 1499599 TI - Absorption and disposition of 14C-labelled oxiracetam in rat, dog and man. AB - The absorption and disposition of the nootropic drug oxiracetam (4-hydroxy-2-oxo pyrrolidine-1-yl acetamide) were studied in rats and dogs (10 mg/kg i.v. and 10, 50 and 3000 mg/kg p.o.) and two healthy male volunteers (800 mg p.o.) using a [14C]-labelled preparation. Peroral absorption of [14C]-oxiracetam was incomplete in rats (28-42%), high in dogs (81-90%) and intermediate in man (about 56%). The rate of absorption was high in all species. Elimination was biphasic and the concentration of total radioactivity in blood and plasma declined rapidly with an initial elimination half-life of 1-3 h in all species. The specific systemic exposure to [14C]-oxiracetam was lowest in the rat, intermediate in the dog and highest in man. In all species the systemically available radioactivity was nearly exclusively excreted in urine in the form of unmetabolized oxiracetam. Whole-body autoradiography and quantitative determination of the radioactivity in various organs following i.v. and p.o. administration of [14C]-oxiracetam to rats demonstrated extensive distribution of the compound with high levels in kidney, liver, lung and skin, and very low levels in the brain. The radioactivity was rapidly eliminated from the body and minimal accumulation was observed upon repeated administration of 10 mg/kg for 8 days. Levels in the brain were still low, but higher than following a single dose, indicating slow diffusion across the blood-brain barrier. In pregnant rats treated with [14C]-oxiracetam radioactivity passed reversibly and to a limited extent through the placenta into fetal tissue. PMID- 1499601 TI - Duration of postoperative immunosuppression assessed by repeated delayed type hypersensitivity skin tests. AB - The duration of postoperative impairment in cell-mediated immunity was assessed by repeated skin testing with seven delayed type common antigens in 15 patients undergoing major elective abdominal surgery compared to a similar testing regimen in 10 healthy volunteers. All were skin tested four times, with 72-hour intervals, and in the surgical patients the first test was applied 2 days before surgery, followed by tests on postoperative days 1, 4 and 7. The tests were read after 48 h. Postoperatively, the skin test area decreased on day 3 (p less than 0.01) and recurred to preoperative levels on day 9. In contrast, the skin test area in the volunteers increased from test to test (p less than 0.001) during the study, confirming a previous finding of a vaccination effect. These results suggest that the postoperative immunosuppression is maintained for about 6-9 days. PMID- 1499600 TI - Ranitidine treatment and cortisol metabolism in man. AB - Experimental evidence suggested that H2-receptor antagonists may inhibit not only hepatic but also adrenal cytochrome P-450 dependent monooxygenases. Therefore, the effects of ranitidine (150 mg b.i.d. over 14 days) on cortisol metabolism and antipyrine clearance have been investigated in nine healthy volunteers. Urinary excretion of 6 beta-hydroxycortisol (6 beta-OHC) and 17-hydroxycorticosteroids (17-OHCS) remained unaffected by ranitidine pretreatment, as did the calculated 6 beta-OHC/17-OHCS ratio. Only marginal effects were observed on antipyrine kinetics and metabolite formation. We conclude that neither adrenal production of corticosteroids nor their hepatic metabolism is affected by ranitidine administration. PMID- 1499602 TI - Effect of recurrent endotoxemia on hemodynamics, lung function and neutrophil activation in sheep. AB - The aim of the study was to find out in which way lung permeability and polymorphonuclear leukocyte (PMNL) functions are modulated under recurrent endotoxin challenge, as it might occur in clinical septic patients. In a sheep model with chronic lung lymph fistula, performing bronchoalveolar lavage (BAL), we investigated the relationship between PMNL function and endothelial as well as epithelial damage in the lung in a sepsis syndrome, using a protocol of recurrent endotoxemia induced by 1 microgram/kg body weight Escherichia coli endotoxin treatment every 12 h over a 5-day period. Pulmonary response showed constantly increased pulmonary arterial pressure at mean values of 24-30 mm Hg. Also, lymph flow did not return to baseline, but remained on a level of 6-9 ml/30 min, after an increase to 12-15 ml/30 min following each endotoxin injection. In contrast, a lower increase in protein clearance was noted upon subsequent endotoxin administration. After initial values of 7-8 ml/30 min following the first endotoxin injection, almost baseline values were measured on the 5th day (3-4 ml/30 min). In systemic hemodynamics, we noted a decrease in cardiac output to 3.0 l/min after the first endotoxin injection, followed by a significant increase to 7 l/min under subsequent endotoxin administration. In PMNL function, we observed an attenuation of the acute response of the decrease in PMNL count, in vitro chemiluminescence response and plasma beta-N-acetylglucosaminidase level. The plasma urea concentration revealed a transient reduction in kidney function. In the epithelial lining fluid (ELF) of the alveoli, total cell count did not change significantly, but the fraction of PMNL increased from 2 to 20% during the 5 days. The ELF/plasma ratios of albumin and total protein did not change significantly. In conclusion, recurrent endotoxemia in a sheep model can produce a hyperdynamic state like in a sepsis syndrome which is further characterized by an initial leakage of the endothelial barrier, only minor affection of the epithelial barrier and by an exhaustion of PMNL function. PMID- 1499603 TI - Suprahepatic vena cava anastomosis of the donor liver to the recipient retrohepatic vena cava in canine liver transplantation. AB - A revised method of the upper caval anastomosis in canine orthotopic liver transplantation is described. It uses the recipient retrohepatic inferior vena cava below the suprahepatic veins for vascular suturing. Ten consecutive operations were performed to assess the feasibility of this method, with special reference to the outflow obstruction at the level of the suprahepatic inferior vena cava. Seven of 10 dogs survived more than 6 days. The cause of death was not related to the outflow obstruction in any instance. Regardless of the duration of survival, free hepatic vein pressures as well as portal vein pressures of all dogs remained in the physiological range even after the skin closures. Based on these observations, we conclude that this approach is safe and reproducible in experimental transplantation of the canine liver. PMID- 1499604 TI - Tumor size, nuclear morphometry, mitotic indices as prognostic factors in axillary-lymph-node-positive breast cancer. AB - The biopsy specimens from the primary tumors of 234 women with axillary-lymph node-positive breast carcinomas (followed up for a mean of 10.9 years) were subjected to interactive morphometric analysis of nine nuclear factors. The proliferative activity of the tumors was estimated by determining two different mitotic indices. Morphometrically determined nuclear factors and mitotic indices showed a significant correlation to the histological grading (p less than 0.0001). Mitotic activity index (MAI; p = 0.018) and volume-corrected mitotic index (M/V index; p = 0.005) accurately predicted the tumor recurrence. Recurrence-free survival was related to the M/V index (p = 0.0003), MAI (p = 0.0024) and tumor size (p = 0.0144). Disease-related survival was determined by the tumor size (p less than 0.0001), M/V index (p = 0.0142) and MAI (p = 0.0492) in that order. On the other hand, the nuclear factors analyzed and the histological grading used had no predictive value (i.e. tumor recurrence, recurrence-free survival or tumor-related survival) in these women. The results indicate that mitotic indices can be successfully applied in place for subjective grading and nuclear morphometry in predicting the disease outcome in patients with axillary-lymph-node-positive breast carcinomas. The mitotic indices provide independent prognostic information in addition to tumor size. The major clinical implications of these results would be to accurately disclose among these women the high-risk patients (i.e. those with high mitotic indices), who might benefit from more agressive adjuvant therapies. PMID- 1499605 TI - Changes in hepatic hemodynamics and oxygen consumption after partial hepatic congestion in dogs. AB - The effects of 66% hepatic congestion (group 2, n = 6) on liver blood flow and hepatic oxygen metabolism were investigated in anesthetized dogs using an ultrasonic transit time flowmeter. The results were compared with those for control dogs (group 1, n = 6) and for 60% hepatectomized dogs (group 3, n = 6) wherein almost the same amount of hepatic parenchyma was removed as was congested in group 2. Portal blood flow (PVF) in group 2 and group 3 decreased similarly to 60 and 63% of the baseline values, respectively (p less than 0.05). Cardiac output (CO) in group 2 and group 3 also decreased significantly in proportion to the decrease in PVF. Among the dogs in group 2, hepatic arterial blood flow (HAF) was fairly well maintained at 86% of the baseline value, despite the decrease of cardiac output, whereas the HAF in group 3 decreased to 49% of the baseline value at 1 h after hepatectomy. The calculated hepatic arterial resistance (HAR) in group 3 increased significantly due to the 60% loss of the hepatic arterial vascular bed. The HAR in group 2, by contrast, became lower than that in group 1, suggesting a compensatory decrease of HAR for the obstructed portal flow to the congested area. These results were well consistent with our angiographic findings (n = 3) that the portal flow to the congested segments was completely obstructed and the congested segments received only an arterial blood supply. The centrilobular hepatocytes of the congested segments showed marked vacuolar degeneration and the total hepatic oxygen consumption in group 2 was reduced (p less than 0.05). However, the decrease in oxygen consumption in group 2 was not so severe as in group 3 (p less than 0.05). These data suggest that some parts of the preserved congested segments were still viable and had the capacity of aerobic metabolism even 4 h after the ligation of the drainage vein of those segments. In this study, the importance of the hepatic arterial flow to the congested segment has been demonstrated. When the congested hepatic segment is to be preserved intraoperatively, care must be taken to maintain the hepatic arterial blood flow during the perioperative period. PMID- 1499606 TI - Hyperthermo-radiosensitivity of esophageal cancer cells with high DNA ploidy in vitro. AB - The in vitro sensitivity to hyperthermia and radiation of esophageal cancer cells obtained from 50 patients was assayed by using the in vitro succinate dehydrogenase inhibition test, and the findings were correlated with data on DNA analysis. The DNA distribution patterns were grouped into types I, II, III and IV, according to the frequency of aneuploid cell populations. Esophageal cancer cells of high ploidy (type IV) had a lower sensitivity to radiation, however, a greater sensitivity to hyperthermia as compared to cells of low ploidy (type II). The sensitivity to hyperthermia was determined as positive in 2 of 8 for type II, in 7 of 25 for type III, and in 9 of 17 for type IV. In contrast, the positive sensitivity rates to radiation in type II, III, and IV were 25.0, 8.0, and 5.9%, respectively. When cells were exposed to combination of radiation with hyperthermia, the positive sensitivity rates increased in all groups (50.0, 44.0 and 70.6% in type II, III, and IV, respectively). There was a significant correlation between mean DNA values and the SD activities following exposure to heat treatment or radiation. These data, describing that cancer cells of high ploidy might have greater sensitivity to hyperthermia compared to radiation, indicate the clinical benefits of hyperthermia in cases of esophageal carcinoma, especially for patients with high DNA ploidy. PMID- 1499607 TI - Involuntary action of the external anal sphincter. Manometric and electromyographic studies. AB - The changes in the rectal neck (anal canal) pressure and electromyography (EMG) of the external anal sphincter and levator ani muscle were studied in 20 dogs before and after internal anal sphincter excision by 2 weeks and monthly up to 10 months. The rectal neck pressure dropped to 41% of the preoperative level. It was then gradually elevated from the beginning of the 1st month following excision till it reached 88% of the level before excision at the 10th month. The external sphincter EMG basal activity after internal sphincterectomy by 2 weeks showed a decrease in the amplitude of the slow and high potential waves. From the 1st to the 7th month after excision, changes in the frequency and amplitude of the waves occurred, and by the 10th month, the external sphincter showed the characteristics of the EMG of both the internal and external anal sphincters. The basal activity of the levator ani muscle increased at the 10th month. As reported previously, the changes in the rectal neck pressure and in the EMG of the external anal sphincter after internal sphincterectomy seem to be due to the histological changes in the muscle and include striated and smooth muscle fiber hypertrophy and proliferation. These changes adapt the external sphincter to serve the function of not only voluntary but also involuntary continence. PMID- 1499608 TI - Analysis of criteria for grading bladder cancer in urine cytological tumor diagnosis by means of an expert system. AB - An inductive expert system was used for the analysis of criteria for grading bladder carcinoma in urine cytological tumor diagnosis. This analysis seems necessary in order to provide a better standardization of grading and to avoid tumor grades, which are rather inhomogeneous with respect to morphology and prognosis. The analysis of the database by the inductive system shows a considerable variation of the cytomorphology of different bladder carcinomas graded as G2 tumors, whereas G1 and G3 tumors are more homogeneous groups respectively. Especially nuclear morphological criteria are important features for the detection of highly differentiated carcinomas, whereas nucleolar features might be helpful to assess the proliferative nature of the carcinoma. The future goal of avoiding a grading system with prognostically inhomogeneous tumor grades seems possible when using an inductive expert system for consultation. PMID- 1499609 TI - Upper tract urothelial tumor after transurethral resection for bladder tumor. AB - We present a retrospective review of 30 patients who developed upper urinary tract tumors (UUTT) after having been diagnosed and treated for a bladder neoplasm. The mean patient age was 63 years (range 54-72). An average of 4.8 (range 1-10) transurethral resections (TUR) had been performed for bladder cancer prior to the appearance of UUTT. The length of time elapsed between the initial bladder TUR and the subsequent diagnosis of UUTT was variable, with increased incidence in the first 24-72 months (63.3% of the cases). In 21 cases (70%) the bladder tumor was multiple and in 28 (93.3%) the tumor was recurrent. In those patients with unilateral vesicoureteral reflux, an increased incidence of UUTT was found in the refluxing renal unit. In patients with poorly differentiated (grade 3 and grade 2-3) bladder tumors, UUTT was of the similar grade of anaplasia in 75% of cases. These observations, together with those previously published in the literature, allow us to recommend the use of excretory urography (IVP) every 2 years during the first 6 years of follow-up in patients treated for recurrent and/or multiple bladder tumor. Thereafter, follow-up would depend upon the individual clinical situation. PMID- 1499610 TI - Impotence due to corporeal veno-occlusive dysfunction: long-term follow-up of venous surgery. AB - Corporeal veno-occlusive dysfunction is an important cause of organic impotence and is characterized by increased flow rates to create and to maintain erection during artificial erection produced by intracavernous saline infusion. Sixty seven patients with this erectile insufficiency underwent penile ligature resection of deep dorsal vein between 1982 and 1986, and were evaluated by nocturnal plethysmography, pharmacocavernometry as well as a questionnaire about their sexual life for long-term follow-up. The surgical procedure was controlled in the operating room by reduction of the erectile flow rates. Thirty-one patients were potent postoperatively and were able to have satisfactory intercourse. Results after resection were slightly better than after simple ligation of the deep dorsal vein. Four patients had penile glans insensibility resulting from the surgical dissection. There were 7 relapses several months after the procedure due to leakage through other deeper veins. Eight failures were due to additional psychogenic disorders or to neurologic disease not accurately diagnosed before the treatment because they all developed normal papaverine-induced erection after venous surgery while before it they only developed a slight tumescence. Reduction of the erectile flow rates within normal values was impossible during surgery in 3 patients. Eleven failures were due to concomitant arterial disease. Resection of the deep dorsal vein can restore penile erection in patients with cavernovenous leakage in about 50% of well selected patients. PMID- 1499611 TI - Penile revascularization in nonresponders to intracavernous injections using a modified microsurgical technique. AB - At certain centers, microsurgical penile revascularization, using different surgical techniques, has gained importance throughout the past years. In general, only patients classified as intracavernous injection nonresponders are subjected to this kind of surgery. Since 1988, revascularization surgery has been performed at our clinic on 19 intracavernous injection nonresponders. The Hauri technique was carried out on the first 6 patients. The last 10 patients underwent modified anastomosis surgery. The inferior epigastric artery and the dorsal penile artery are anastomosed, one behind the other, end-to-side, to the dorsal penile vein. This results in a more simple procedure with assurance of flow. The Virag technique was performed on 3 patients. 18 patients achieved erections with or without the aid of intracavernous injections (at a mean follow-up of 13.4 months). 11 patients were capable of spontaneous erections, whereby it was particularly noted that 8 of the 10 patients undergoing the modified technique achieved spontaneous erections. The results demonstrate that intracavernous injection nonresponders benefit from revascularization surgery. PMID- 1499612 TI - Can fine needle aspiration biopsy detect incidental prostatic carcinoma (T1) prior to TUR? AB - The purpose of this study was to find out whether randomly taken fine needle aspiration biopsy (FNA) can detect incidental prostatic carcinoma prior to transurethral resection (TUR) and what are the effects of local tumor stage and grade on detection rate. Biopsies were taken from 344 patients, who came to hospitals for elective TUR without clinical evidence of prostatic carcinoma. Histologic examination of the TUR material showed prostatic carcinoma in 49 cases (14%). Sufficient material for cytologic examination was found in 343 cases. Of the 16 cases of T1a carcinoma in histologic examination, cytology found only 1, which was a G3 carcinoma. Of 33 T1b carcinoma in histologic examination, cytology found 6 and an additional 7 were suspect findings. Out of 6 G3 tumors in histologic examination, cytology showed 4. In our hands the proportion of false negative cytologic findings in randomly taken FNA was so large that routine use of random FNA prior to TUR or as a screening procedure cannot be recommended, but positive FNA finding can be regarded as cancer. PMID- 1499613 TI - Horseshoe kidney: the impact of percutaneous surgery. AB - Six patients with a stone disease and/or ureteropelvic junction obstruction in a horseshoe kidney underwent percutaneous surgery. No major complications were observed and only 1 patient presented residual fragments in the lower calyx 3 months after treatment. The special features of the use of percutaneous nephrolithotomy and endopyelotomy for this anomaly are described. PMID- 1499614 TI - Rationale of urodynamic assessment in adult enuresis. AB - Between October 1988 and November 1990, 39 adult patients (average age 18.5 years) with enuresis underwent urodynamic evaluation. Filling cystometry was performed transurethrally using normal saline in the supine position. Abnormal cystometric findings were observed in 11 patients (28.2%), unstable bladder being the most common pathology (n = 7). Abnormal cystometric findings did not correlate with sex, age and diurnal symptoms of the patients. The only difference between pathologic and normal cystometry groups was the functional bladder capacity which is found to be reduced significantly in the former group. Cystometry does not contribute to the diagnosis of enuresis but helps to enlighten its physiopathology. PMID- 1499615 TI - Effects of pentoxifylline in the hamster zona-free oocyte spermatozoa penetration assay and on spermatozoa transmembrane migration motility. AB - The effects of pentoxifylline on capacitation, acrosome reaction and motility of spermatozoa in vitro were evaluated by the hamster zona-free oocyte penetration assay and the transmembrane migration method, respectively. The improvement in penetration capacity by the addition of pentoxifylline 40 min before coincubation had a trend toward statistical significance (0.05 less than less than 0.1) in normal fertile men and had statistical significance (p less than 0.05) in asthenospermic patients. There was no improvement by the addition of pentoxifylline 16 h before coincubation. Pentoxifylline significantly increased sperm motility in both normal (p less than 0.001) and asthenospermic patients (p less than 0.05) in the transmembrane migration method. This study showed that pentoxifylline could be used as a stimulant of in vitro sperm motility in male infertility. PMID- 1499616 TI - Measurement of blood flow in the parameatal foreskin flap for urethroplasty in hypospadias repair. AB - During the one-stage repair of hypospadias the blood flow of the parameatal-based foreskin flap was measured in 30 patients by using laser Doppler velocimetry. The mean blood flow in the penile foreskin was estimated to be 15 ml/min/100 g and it increased to 150-200% after the induction of anesthesia, and then decreased to 72% at the tip of the created parameatal foreskin flap. Topical application of papaverine hydrochloride restored the flow to the preincision level in half of the cases. The parameatal foreskin flap, both in the form of a manta-wing and in extended circumferential form, appears to have an enough microcirculation suitable for one-stage repair (OUPF II and OUPF IV, respectively) of hypospadias. PMID- 1499617 TI - Erythropoietin in renal cell carcinoma: evaluation of its usefulness as a tumor marker. AB - Erythropoietin levels in serum were analyzed in 165 patients with renal cell carcinoma. All samples were taken before therapy and stored at -80 degrees C. Erythropoietin, a glucoprotein produced by the renal cortex was quantified by an enzyme immunoassay. Fifty-five of 165 patients (33%) had elevated serum levels. In patients with metastatic disease (M+), elevated levels were found in 24 of 65 cases (38%). Patients with high-grade tumors had significantly more often increased erythropoietin than those with low-grade tumors. No correlation between erythrocytosis and elevation of erythropoietin in serum was found. There was a significant difference in survival between patients with normal and patients with elevated erythropoietin levels (p = 0.013). The study shows that erythropoietin is a tumor marker with a low sensitivity. However, it correlates with stage and grade and provides prognostic information. PMID- 1499618 TI - Intrascrotal uterus in a normal male phenotype. PMID- 1499619 TI - Malignant priapism due to a huge renal carcinoma. AB - Metastases to the penis from renal cell carcinoma producing priapism are very rare, as only 18 cases have been described since 1964. We present an additional case of priapism due to massive metastatic involvement of the corpora cavernosa in a patient with huge renal cell carcinoma, 28 cm in diameter, discussing the possible pathogenetic mechanism of such a rare condition. PMID- 1499620 TI - Peritoneum-preserving radical nephrectomy in a patient on continuous ambulatory peritoneal dialysis. AB - We describe a pararectus retroperitoneal approach for radical nephrectomy in a patient on chronic ambulatory peritoneal dialysis. This approach allows early ligation of the renal pedicle pre-operatively and immediate resumption of peritoneal dialysis post-operatively. PMID- 1499621 TI - Malignant mesothelioma of the testicular tunica vaginalis. AB - The histological, histochemical and immunohistochemical features of a malignant mesothelioma of the tunica vaginalis testis in a 69-year-old patient are described. The mesothelial derivation of the tumor was confirmed using a panel of selected antibodies. Malignant mesothelioma of the testicular tunica vaginalis is a rare tumor that must be considered so that appropriate treatment can be instituted. PMID- 1499622 TI - Prognostic factors in superficial bladder cancer. A review. PMID- 1499623 TI - Clinical significance of flow cytometric deoxyribonucleic acid measurements of deparaffinized specimens in bladder tumors. AB - A retrospective study of flow cytometric measurements on paraffin-embedded tumor specimens from 188 patients with bladder tumor was conducted. Results were analyzed in combination with the morphological variation in bladder tumors. It was found that the deoxyribonucleic acid (DNA) ploidy pattern, the degree of infiltration and the multiplicity of bladder tumor were closely related with tumor recurrence, among which the DNA ploidy pattern was most significant. In aneuploid bladder tumors, the recurrence rate and the mean annual recurrence frequency were 76.7% and 1.46, respectively, and in the diploid bladder tumors, they were 18.7% and 0.33, respectively. Aneuploidy was the most indicative parameter of recurrence in bladder tumors. In addition, according to the DNA content and the ploidy level of the aneuploid cell lines, the aneuploid tumors in our group were divided into four types, namely tetraploid tumors, noneuploid tumors with an DNA index (DI) less than or equal to 1.5, hypotetraploid tumors and aneuploid tumors with several cell lines. The results showed that the recurrence rate of tetraploid tumors was relatively lower, and it became higher and higher in the following order: noneuploid tumors with DI less than or equal to 1.5, noneuploid tumors with DI greater than 1.5, and two-aneuploid tumors. This indicates that there are different biological behaviors in tumors with different ploidy patterns. Finally, the correlation between the DNA ploidy pattern and tumor metastases was also discussed. PMID- 1499624 TI - Review of cytometric methods in the assessment of prognosis in transitional cell bladder cancer. PMID- 1499625 TI - Extracorporeal shock wave lithotripsy with ultrasound-guided lithostar plus. AB - Since 1989, the Siemens lithostar plus, an upgrade of the lithostar with the ultrasonically guided overhead module, has been available for clinical use. This unit may be used for the treatment of either biliary or urinary calculi. We report on 75 patients with urinary calculi treated between March 1989 and June 1990 with the lithostar overhead module. Stone localization showed a rate of: caliceal stones 33.5%, pelvic stones 44%, upper ureteral stones 9.3% and lower ureter stones 13%. The overall disintegration rate was 86%, with a stone-free rate after 3 months of 78%. PMID- 1499626 TI - Topical chemoprophylaxis of superficial bladder cancer with mitomycin C and adjuvant hyaluronidase. AB - The effect of intravesical instillation of 200,000 IU hyaluronidase in addition to mitomycin C as chemoprophylaxis of superficial bladder cancer was evaluated. Based on our result of a previous study that this approach results in a significantly reduced recurrence rate (7.1 versus 32.1%), 43 patients undergoing transurethral resection of Ta-T1 tumors were retrospectively analyzed after a mean observation period of 48.5 months. During the 2 years of prophylactic therapy, tumor recurrence was seen in 6 patients (13.9%). Of the 37 patients who remained recurrence-free under treatment, 5 (13.5%) had recurrent tumors later during a mean observation period of 24.5 (18-42) months after treatment. These values are significantly lower than those obtained previously from a group of 63 patients treated with mitomycin alone, with recurrence rates of 33.3% during chemoprophylaxis and 26.2% thereafter (mean observation period 50.4 months). It appears that additive hyaluronidase enhances the local effect of mitomycin C in the intravesical chemoprophylaxis of bladder cancer, presumably by improving diffusion into the bladder mucosa and catalyzing the breakdown of a hyaluronic acid contained in a protective halo around malignant urothelial cells. PMID- 1499627 TI - Treatment of advanced bladder cancer by submucosal injection of methotrexate in the anorectal area. AB - In 1988, Shafik et al. presented their first attempt to apply cytostatics in the treatment of pelvic malignancies. Experimentally and clinically, they studied the anal route for administration of methotrexate, and their first results showed that higher concentration of drugs can be achieved in the bladder wall compared to that in serum. Since December 1988, we have been engaged in experimental and clinical investigations of the possibilities this method might reveal. Experiments with animals have proven that submucosal injection of the cytostatic agent does not induce local changes. The clinical trial on 20 patients with tumors of stage T2-T4 has not shown side effects, either local or systemic. The treatment was well tolerated by the patients. Anorexia has been reported in 3, elevated temperature in 2 and leukopenia in 4 of 20 patients. Complete response has been documented in 3 (15%), partial response in 3 (15%), stabilization in 5 (25%) and progression of the disease in 9 (45%) of the patients. Mean duration of remissions was 10.3 months (range 9-12). The distribution of submucously injected contrast medium into the anorectal area has been studied by computerized tomography in 4 of the patients. Although our results do not support the original estimates of the inventors of the method, its ease of application, the possibility of out-patient administration and negligible side effects are sufficient arguments for performing further experimental and clinical studies. PMID- 1499628 TI - Frequency of urogenital tuberculosis in an unselected autopsy series from 1928 to 1949 and 1976 to 1989. AB - The evaluation of a total of 12,211 autopsy protocols prior to the introduction of chemotherapy (1928-1949) and in the recent years (1976-1989) had the following results: the frequency of renal tuberculosis has dropped from 2.0 to 0.6% of all autopsies in men and from 1.7 to 0.9% in women. While the frequency of miliary tuberculosis infections in general has decreased to about one fourth (from 2.7 to 0.6% of all autopsies), renal involvement in patients with miliary tuberculosis has rather increased (from 35.4 to 52.2 for men and from 37.5 to 68.0% for women). The frequency of miliary tuberculosis of the kidneys was two times higher in girls than in boys (3.8% of girls and 1.8% of boys). Tuberculosis of the renal pelvis, ureter or urinary bladder secondary to a renal tuberculous infection has decreased from 65 to 4.3% of all tuberculous infections with renal involvement in males and from 25 to 0% in females. In the second period, the frequency of genital tuberculosis has in all dropped to about one tenth. PMID- 1499629 TI - The Wardill test: does it predict future voiding flow? AB - A prospective study was undertaken to assess the predictive value of measuring the peak flow rate at completion of a transurethral prostatectomy with suprapubic pressure (the Wardill test). Twenty-six patients had their expressed flow rate measured on applying a standardised suprapubic pressure and compared to their peak flow rate measured at least 6 weeks postoperatively. No significant correlation was found to exist between the two variables. PMID- 1499630 TI - Inhibitors of stone formation in hypercalciuric children with and without stone disease. AB - The extretion of two inhibitors of urinary stone formation (citrate, magnesium) was evaluated in 71 hypercalciuric children and 50 controls. Patients were classified into two groups: 42 nonstone former (NSF), 22 boys and 20 girls, 3-14 years old, and 29 stone formers (SF), 18 boys and 11 girls, 2.5-18 years old. Our study was unable to show significant differences in magnesium and citrate urinary outputs between controls and patient groups. The Mg/Ca ratio was found significantly lower in hypercalcuric children than in controls (p less than 0.001), but not between NSF and SF patients. Our data demonstrated that both NSF and SF groups had a significantly lower citrate/Ca ratio than controls (p less than 0.001), also it was lower in SF than in NSF (p less than 0.05). We found no significant difference in citrate excretion between boys and girls neither in patients nor in controls. PMID- 1499631 TI - Histopathological alterations of deep dorsal penile vein in venogenic impotence. AB - The mechanism and hemodynamics of penile veins in erection have long been a matter of controversy and hypotheses. With the intention to develop a new concept of venous ultrastructure in penile venous insufficiency, we studied the histopathology of 13 dorsal penile veins obtained from important patients during venous ligation because of proven venous leakage. Besides, 1 normal deep dorsal vein taken from a volunteer who underwent another type of penile operation was also examined. All sections were stained with hematoxylineosin, Gomori trichrome, periodic acid-Schiff, Gomori reticulum and Verhoeff elastic stains. All 13 veins showed some significant histological changes namely nodular hypertrophy in 7, nodular atrophy in 2, diffuse atrophy in 2, diffuse hypertrophy in 1 and minimal changes in 1. In general, the dominating histological appearance was hypertrophy of the muscular pattern and enhancement of collagenization. None of these alterations was prevalent in the normal control. The cause and the result relationship between venous leakage and the mentioned histological changes still remains a matter of debate. PMID- 1499632 TI - Effect of external beam radiotherapy on prostatic carcinoma DNA content as measured by static image cytometry. AB - Static image cytometry was used to study the effect of radiotherapy on the DNA content of prostatic carcinoma. Feulgen-stained specimens from 50 patients before and after radiotherapy were examined. The DNA index increased significantly after treatment (p less than 0.03), and it occurred equally in those with low (less than 1.5) and high (greater than or equal to 1.5) indices. The level of the initial DNA index was significantly related to the rate of symptomatic progression (p less than 0.05). The initial change in and final DNA indices were not related to survival however. There was a significant increase in Gleason score (p = 0.001) and histological grade (p = 0.01) after irradiation and, when taken individually, the degree of change was related to survival in both, p = 0.05 and 0.004, respectively. As Gleason score, Mayo grade and clinical stage were not independent variables; none of them was related to survival when corrected for the other factors. Thus, DNA content or ploidy, as well as Mayo grade and Gleason score, increases in recurrent tumor after radiotherapy. This may be of importance when considering what treatment to use and how intensively the patients should be followed up. PMID- 1499633 TI - The role of serum laminin P1 in the diagnosis of transitional cell carcinoma of the bladder. AB - In order to explore the possible role of serum laminin P1 in the diagnosis of transitional cell carcinoma (Tcc) of the bladder, the sera of 50 healthy control subjects and of 35 bladder-cancerous patients were measured by radioimmunoassay. In 27 patients (77%), the serum level was elevated above the upper limit of normal range. Statistically significant elevation could be determined in all stages and grades of Tcc of the bladder compared to those of normal subjects (mean +/- SD: 1.18 +/- 0.16 kU/l). Deterioration of the clinical stages or pathologic grades of the tumor was associated with a progressive increase in the mean values of serum laminin P1. A longer study with serial determination is planned to assess the prognostic significance of serum laminin in bladder cancer patients. PMID- 1499634 TI - A system for focal intracavitary irradiation of bladder cancer with remote iridium-192 afterloading. AB - An afterloading system for remote-control focal intracavitary irradiation of bladder cancer is presented. With 192Ir as radiation source, we demonstrated the practicability of the method in 23 chinchilla rabbits. A system for focal intracavitary irradiation of bladder cancer in humans was developed. A guiding tube with an inflatable balloon led to a reproducible vesical diameter. The intravesical part of the tube was shielded with lead and had a slit for focal radiation exposure. Three variant guiding tubes with different positions of the slit were designed to allow irradiation of any part of the bladder. The application is planned in patients with locally advanced tumors who refuse radical cystectomy or who are medically inoperable. PMID- 1499635 TI - Studies on the retention of the mucous-membrane-adhesive anticancer agent hydroxypropylcellulose doxorubicin. AB - Incorporation of hydroxypropylcellulose (HPC-)doxorubicin, which we developed as a mucous-membrane-adhesive drug preparation, was instilled into the urinary bladder in 10 clinical cases. Tumor of the urinary bladder was a single tumor in all 10 cases, and preclinical histology showed transitional cell carcinoma, grade 1 or 2, and a lower stage than T1. HPC-doxorubicin, 20 mg/20 ml, was administered in 5 cases, and the other 5 cases received the conventional aqueous doxorubicin, 20 mg/20 ml by way of a catheter and the urethra. Cold punch biopsy was performed after 3 days of instillation, and the incorporation of doxorubicin into both tumorous and normal tissue was measured by high-pressure liquid chromatography. After 3 days, it was found that in the HPC-doxorubicin-administered group, doxorubicin was detected in both tumorous and normal tissue, but it was not detected in either tissue after aqueous doxorubicin administration. In 5 cases of the HPC-doxorubicin group, doxorubicin levels in the tumorous and normal tissue were examined, and it was found that significantly more doxorubicin was detected in the tumorous tissues. Thus, it may be said that our HPC-doxorubicin remained longer within the urinary bladder than the conventional aqueous doxorubicin preparation. Instilled HPC-doxorubicin is more highly concentrated in the tumorous tissue than in the normal bladder tissue, and thus, HPC-compounded anticancer drugs may be therapeutically more useful. PMID- 1499636 TI - Lymphangioma of the spermatic cord and tunica vaginalis in children. PMID- 1499637 TI - Perineal versus anal submucosal injection of chemotherapeutic drugs. PMID- 1499638 TI - The human renal 25-hydroxyvitamin D3-1 alpha-hydroxylase: properties studied by isotope-dilution mass spectrometry. AB - The renal 25-hydroxyvitamin D3-1 alpha-hydroxylase activity has been measured in normal human kidney cortex, using a highly specific assay based on isotope dilution mass spectrometry. The cortex was obtained from kidneys removed due to renal tumours. The subcellular distribution of 25-hydroxyvitamin D3-1 alpha hydroxylase activity was studied. Enzyme activity was only observed in the mitochondrial fraction. Mitochondria from non-tumourous kidney cortex had a Vmax of 0.17 +/- 0.02 pmol min-1 mg-1 protein and the apparent Km was in the range of 14 mumol l-1. There was a tendency to a higher 25-hydroxyvitamin D3-1 alpha hydroxylase activity in preparations from male kidney (0.21 +/- 0.03 pmol min-1 mg-1 protein) than female (0.12 +/- 0.02, P less than 0.05). A significant inverse correlation between serum phosphate and 25-hydroxyvitamin D3-1 alpha hydroxylase activity was found. No correlation was observed between enzyme activity and serum levels of 1,25-dihydroxyvitamin D (total and free index), PTH, total calcium or ionized calcium. The results indicate that there is a sex difference in human 25-hydroxyvitamin D3-1 alpha-hydroxylase activity similar to the one observed in laboratory animals. Furthermore, the data support the hypothesis that serum phosphate is a major regulator of 1,25-dihydroxyvitamin D3 production in man. PMID- 1499639 TI - Uptake of chylomicron remnant retinyl esters in human leukocytes in vivo. AB - Retinoids have been successfully used in the treatment of some forms of leukaemia, suggesting that such cells have an efficient uptake mechanism for circulating retinoids. Therefore, we have studied the uptake of lipoprotein associated retinyl esters in human leukocytes in vivo. After an oral load of 100 mumol retinyl palmitate (30,000 retinol equivalents) per square meter given to healthy adults, the concentration of retinoids in circulating leukocytes was determined. A peak was measured after 5 h, which coincided with a peak of retinyl esters in plasma. To test whether low-density lipoprotein receptors are necessary for the postprandial uptake of retinoids, we studied retinoid uptake in leukocytes from two patients homozygous for familial hypercholesterolaemia. After an oral load of retinoids we found that leukocytes from these patients took up at least as much retinoid as leukocytes in normal individuals, suggesting that uptake of chylomicron remnant retinyl esters may proceed independent of the low density lipoprotein receptor. The expression of mRNA for the low density lipoprotein receptor-related protein, which is a putative chylomicron remnant receptor, was similar in leukocytes from a patient homozygous for familial hypercholesterolaemia and normal individuals. Six hours after vitamin A administration, recovery of unesterified retinol was 71% in normal leukocytes, however, only 9% unesterified retinol was recovered in leukocytes from the two patients with familial hypercholesterolaemia. Thus, the apparent rate of retinyl ester hydrolysis was markedly reduced in leukocytes from these patients, indicating different intracellular traffic of chylomicron remnants in normal individuals and patients homozygous for familial hypercholesterolaemia. PMID- 1499640 TI - Incomplete suppression of hepatic glucose production in non-insulin dependent diabetes mellitus measured with [6,6-2H2]glucose enriched glucose infusion during hyperinsulinaemic euglycaemic clamps. AB - We have minimized methodological errors in the isotope dilution technique by using stable isotope, [6,6-2H2]glucose, thus avoiding the problem of contamination of tritiated glucose tracers and, by maintaining a constant plasma tracer enrichment have reduced error due to mixing transients. Using these modifications we have calculated hepatic glucose production in 20 patients with non-insulin-dependent diabetes mellitus during low (1 mU kg-1 min-1) and high (8 mU kg-1 min-1) dose insulin infusions. Mean fasting hepatic glucose production was 14.2 +/- 0.8 mumol kg-1 min-1. This suppressed by only 68% to 4.6 +/- 0.8 mumol kg-1 min-1 during the low-dose insulin infusion (plasma insulin 0.85 +/- 0.05 nmol l-1) and did not suppress further during the high-dose insulin infusion (plasma insulin 14.55 +/- 0.83 nmol l-1). Hepatic glucose production was significantly higher than zero throughout the study. Thus, we have found that minimization of known errors in the isotope dilution technique results in physiologically plausible and significantly positive values for hepatic glucose production indicating that the liver is resistant to insulin in patients with non insulin-dependent diabetes mellitus. PMID- 1499641 TI - Identification in human urine of a natural growth inhibitor for cells derived from solid paediatric tumours. AB - Partially purified urine of healthy human subjects contains several fractions able to inhibit the proliferation of cultured human neuroblastoma cells. One of the most active fractions was further analysed by gas chromatography-mass spectrometry and shown to contain genistein, a substance formed in the human body from precursors obtained by diet. Synthetic genistein was able to inhibit the proliferation of human neuroblastoma cells with a half-maximal effect at 5-10 mumol l-1 concentrations. Genistein displayed similar potencies in inhibiting the proliferation of cells derived from various other solid pediatric tumours. Our results suggest that genistein is a natural antineoplastic agent present in diet and that it could be useful for the therapy of paediatric tumours. PMID- 1499642 TI - Human recombinant C5a enhances lipopolysaccharide-induced synthesis of interleukin-6 by human monocytes. AB - The effect of human recombinant C5a (hrC5a) on the synthesis of interleukin-6 (IL 6) was studied in human monocytes. Monocytes incubated in the absence of hrC5a and of bacterial lipopolysaccharide (LPS) produced only low amounts (less than 100 U/2 x 10(6) cells/16 h) of IL-6 activity. LPS in concentrations from 10 pg ml 1 to 10 ng ml-1 greatly stimulated the synthesis of IL-6 to about 50.000 U/10(6) cells/16 h. When hrC5a was added to the monocyte media maximal IL-6 synthesis was reached at lower LPS concentrations, i.e. at 0.1 ng ml-1 LPS in the presence of 100 ng ml-1 hrC5a. Maximal IL-6 production was not significantly enhanced by hrC5a. Metabolic labelling with [35S]-methionine followed by immunoprecipitation of IL-6 showed that the increased IL-6 activity in the medium of hrC5a treated monocytes was due to a stimulation of the de novo synthesis of IL-6. Increased amounts of IL-6 mRNA were found in monocytes treated with LPS and hrC5a compared with monocytes stimulated only with LPS. HrC5a prolonged the elevation of IL-6 mRNA levels after stimulation of monocytes with LPS. HrC5a thus enhanced the LPS induced synthesis of IL-6 by human monocytes. PMID- 1499643 TI - Regional effects and clearance of endothelin-1 across pulmonary and splanchnic circulation. AB - To determine the impact of i.v. endothelin-1 on systemic, pulmonary and splanchnic circulation, as well as the peptide's regional clearance, hepatic venous and right heart catheterization was performed in healthy volunteers. During the peptide's continuous i.v. administration (0.4 pmol x kg-1 x min-1, 60 min) its plasma concentration rose from 2.1 +/- 0.5 to 9.5 +/- 5.3 pmol/l (pulmonary artery), from 2.1 +/- 0.9 to 5.0 +/- 1.6 pmol/l (femoral artery), and from 1.5 +/- 0.6 to 2.9 +/- 1.2 pmol/l (hepatic vein). This was accompanied by an increase in mean systolic arterial pressure from 127 +/- 14 to 131 +/- 12 mmHg (P less than 0.05). Concomitantly, cardiac output and heart rate decreased from 7.0 +/- 1.1 to 5.8 +/- 1.0 l/min and from 63 +/- 6 to 56 +/- 5 beats/min, respectively, while total vascular resistance increased from 964 +/- 273 to 1204 +/- 338 dyn x cm x s-5 (P less than 0.01). No major changes in pulmonary circulation were observed, while splanchnic vascular resistance increased from 4472 +/- 1056 to 5361 +/- 1420 dyn x cm x s-5 (P less than 0.01) and estimated hepatic blood flow decreased from 1403 +/- 218 to 1218 +/- 219 ml min-1 (P less than 0.01). During endothelin-1 infusion the pulmonary vascular bed accounted for approximately 53% of the peptide's overall disposal.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1499644 TI - Glucagon-like peptide-1 cells in the gastrointestinal tract and pancreas of rat, pig and man. AB - A highly specific monoclonal antibody directed against the C-terminal part of glucagon-like peptide-1 (GLP-1) was raised to immunohistochemically evaluate the distribution of GLP-1 containing cells in the entire gastrointestinal tract including pancreas of rat, pig and man. In the pancreas GLP-1-immunoreactive cells were found variously shaped and predominantly located in the periphery of the islets. Ultrastructurally, GLP-1 was co-localized with glucagon in the alpha granula of A-cells and was mainly restricted to the electrondense core. In the intestine open type cells reaching the lumen via a slender apical process were stained with the GLP-1 antibody. They occurred in all parts of the crypts but predominantly in the basal portion. The density of GLP-1 immunoreactive cells varied between species in a characteristic order: rat greater than pig greater than man. In pig and human gut a large number of cells occurred in the distal jejunum and ileum. A continuous increase of cell densities was found from the proximal to the distal colon resulting in highest numbers in the rectum. In rats the highest cell density occurred in the ileum. Again, a continuous increase of GLP-1-positive cell numbers was evident from the proximal to the distal portion of small and large bowel. GLP-1 was partly co-localized with PYY. The GLP-1 positive cells appeared electronmicroscopically as L-cells with the typical large granula. This morphological data indicates that GLP-1-releasing cells in the small intestine are appropriately positioned in the distal part to sense and respond to the presence of nutrients that have escaped the absorptive surface of the upper small intestine. PMID- 1499645 TI - Effects of interferon alpha on insulin binding and glucose transport in human adipocytes. AB - We have previously demonstrated that interferon administration impairs glucose tolerance and causes insulin resistance in healthy man. Whether this is a direct effect of interferon is not known. The present study was undertaken to examine directly the effect of interferon alpha on insulin binding and action on glucose transport in isolated human adipocytes. Different concentrations of interferon alpha (range 10(-3)-10(5) IU ml-1) and different incubation times (0-5-24 h) with interferon were employed. Acute and 5-h and 24-h exposure of human adipocytes to 10(-2)-10 IU ml-1 of interferon increased the high affinity binding of 125I insulin (P less than 0.05). In contrast, human interferon alpha had no effect on insulin binding in rat adipocytes. In short-term studies interferon had no effect on 14C-glucose transport clearance. 24-h preincubation of human adipocytes with 10(-2), 10, 10(4) IU ml-1 interferon increased maximally-insulin stimulated 14C glucose transport clearance (P less than 0.05) and glucose transport responsiveness to insulin was enhanced by 24% (P less than 0.05) in cells exposed to 10(-2) IU ml-1 interferon. After 5 and 24-h preincubations with interferon we observed modest changes in glucose transport sensitivity to moderate concentrations of insulin (50-100 pM) with upregulation in the presence of 10(-2) 10 IU ml-1 interferon and downregulation in the presence of 10(4)-10(5) IUm ml-1 interferon (P less than 0.05). The insulin sensitivity index (ED50) did not change.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1499646 TI - Neurogenic responses of urethra isolated from the dog. AB - Electrical transmural stimulation evoked contraction and relaxation in isolated urethral circular muscle of the dog. The responses were abolished by tetrodotoxin, indicating their neurogenic origin. The contractile force in the middle urethra was greater than that in the proximal and distal urethra. The contractions were not affected by atropine and propranolol, but were completely inhibited by phenoxybenzamine, prazosin and guanethidine. In preparations contracted with prostaglandin F2 alpha, electrical stimulation induced frequency dependent relaxation in all urethral portions. Atropine, phenoxybenzamine, prazosin and guanethidine had no effect on the relaxation, while propranolol slightly attenuated the relaxation induced at the highest frequency used (5 Hz). The non-adrenergic, non-cholinergic relaxation was also not affected by ketanserin, methysergide, diphenhydramine, alpha,beta-methylene ATP or capsaicin. Exogenously applied phenylephrine and clonidine both produced contractions but the maximal response to clonidine was much smaller than that to phenylephrine. Acetylcholine produced no or feeble contractions. In the preparations contracted with prostaglandin F2 alpha, isoproterenol and vasoactive intestinal polypeptide (VIP) produced relaxation. These results suggest that the circular muscle of dog urethra is reciprocally innervated by sympathetic adrenergic and non-adrenergic, non-cholinergic nerves, and that the neurogenic responses are markedly affected by muscle tension and the portion of the urethra examined. PMID- 1499647 TI - Characterization of the peripheral action of neuropeptide K on the rat cardiovascular system. AB - The effects of neuropeptide K (NPK) were measured on mean arterial pressure (MAP) and heart rate (HR) after i.v. injection in urethane-anesthetized rats. NPK (6.5 and 32.5 nmol/kg) produced sustained decreases in MAP and elicited increases in HR. Whereas the NPK-induced tachycardia lasted more than 30 min at 32.5 nmol/kg, a latent and long-lasting bradycardia appeared from 20 min after injection of 6.5 nmol/kg. The initial tachycardia was converted to bradycardia by metoprolol but remained unaffected by hexamethonium, atropine and naloxone. These four treatments, however, prevented the bradycardiac response to NPK at 30 min. Whereas phentolamine, idazoxan, bilateral adrenalectomy and chemical sympathectomy with 6-hydroxydopamine (6-OHDA) preserved the initial tachycardia induced by NPK, they converted the decrease in HR to a tachycardiac response at 30 min. The vasodepressor response to NPK was significantly enhanced by bilateral adrenalectomy, chemical sympathectomy and metoprolol but remained unaffected by all other treatments. Neither the MAP nor the HR responses to NPK were affected by indomethacin. These results suggest that NPK can accelerate HR through non reflex activation of the sympathoadrenal system. The secondary bradycardia induced by NPK may be due to a vagal reflex while the vasodepressor response to NPK is probably attributable to a direct action mediated by specific receptors on arterial blood vessels. Thus, NPK is considered as the most potent biologically active tachykinin so far described on the rat cardiovascular system. PMID- 1499648 TI - The protein kinase C activators, phorbol 12-myristate,13-acetate and phorbol 12,13-dibutyrate, are convulsant in the pico-nanomolar range in mice. AB - Administration of phorbol 12-myristate,13-acetate (PMA, 10 fmol-10 nmol) or phorbol 12,13-dibutyrate (PDB, 0.2-495 nmol) (i.c.v.) to mice induced: hindlimb scratching, tremor, myoclonic jerks, hyperlocomotion, clonic seizure, followed by death or recovery. CD50 values for clonic seizures for PMA and PDB were 1.0 pmol and 1.2 nmol. 4-alpha-Phorbol (68-686 nmol) was inactive. The effects of PDB (24 247 nmol) were reduced by pretreatment with staurosporine (30 nmol, i.c.v.). Protein kinase C activators are potent convulsants in vivo. PMID- 1499649 TI - The effect of hydrochlorothiazide on the enhanced coughing associated with treatment with enalapril. AB - The effect of hydrochlorothiazide, a diuretic which is used in the treatment not only of edema but also of hypertension, on coughs associated with treatment with enalapril was studied in guinea pigs. Chronic treatment with enalapril markedly and dose dependently enhanced the number of capsaicin-induced coughs. However, chronic treatment with hydrochlorothiazide significantly reduced the number of coughs associated with enalapril treatment, also in a dose-dependent manner. These results suggest that diuretics might be used to reduce the coughing associated with treatment with inhibitors of angiotensin-converting enzyme in patients with hypertension. PMID- 1499650 TI - External ATP antagonizes the effect of potassium channel openers in guinea-pig ventricular papillary muscle. AB - Right ventricular papillary muscles of the guinea-pig heart were electrically stimulated. Cromakalim 10-100 microM and Ro 31-6930 3 microM depressed the contractile force and shortened the duration of action potentials. Glibenclamide 0.3-3 microM, ATP 100 microM and alpha, beta-methylene ATP (alpha, beta-meATP) 30 microM antagonized these effects. Suramin 300 microM failed to reverse the alpha, beta-meATP-evoked antagonism of the action of cromakalim. It is concluded that both intra- and extracellular ATP may interfere with potassium channel openers and that extracellular ATP does not act via the known P2-purinoceptor subtypes. PMID- 1499651 TI - CCK-8-stimulated insulin secretion in vivo is mediated by CCKA receptors. AB - The effects of the cholecystokinin A (CCKA) receptor antagonist, L-364,718, and the CCKB receptor antagonist, L-365,260, on CCK-8-stimulated insulin secretion were studied in vivo in the mouse. It was found that CCK-8-stimulated insulin secretion was suppressed by L-364,718 at a low dose level (0.078 mumol/kg). In contrast, L-365,260 caused a partial inhibition of CCK-8-stimulated insulin release only at the high dose level (24 mumol/kg). It is concluded that the CCK-8 stimulated insulin release in vivo is mediated by CCK receptors of the CCKA subtype. PMID- 1499652 TI - Glibenclamide does not block arterial relaxation caused by vasoactive intestinal polypeptide. AB - Vasoactive intestinal polypeptide (VIP) caused a concentration-dependent relaxation in rabbit mesenteric artery with intact endothelium. The relaxant response to VIP was inhibited by the removal of the endothelium or by pretreatment with methylene blue, but not by pretreatment with glibenclamide. A small but significant relaxant response to VIP in the endothelium-denuded artery was also unaffected by glibenclamide. These findings indicate that ATP-sensitive K+ channels are not involved in the endothelium-dependent or endothelium independent arterial relaxation elicited by VIP. PMID- 1499653 TI - Probenecid pretreatment enhances anticonvulsant action of NBQX in mice. AB - NBQX (2,3-dihydroxy-6-nitro-7-sulfamoyl-benzo(F)quinoxaline) was studied following intravenous administration to mice. Maximal electroshock seizures were suppressed by low doses of NBQX (ED50 = 13 mg/kg) but effects had dissipated by 10 min after a dose of 25 mg/kg. Coadministration of the transport inhibitor probenecid (p-(dipropylsulphamoyl)-benzoic acid) enhanced and prolonged the anticonvulsant action of NBQX and also enhanced and prolonged ataxia. NBQX may be rapidly eliminated by a process sensitive to probenecid. PMID- 1499654 TI - Effect of haloperidol and clozapine on (+)SKF 10,047-induced dopamine release: role of 5-HT3 receptors. AB - (+)SKF 10,047 preferentially increased dopamine release in the nucleus accumbens compared to the striatum. Dopamine output was evaluated in the same freely moving rats by trans-cerebral dialysis. Clozapine and DAU 6215, a 5HT3 antagonist, which itself did not modify dopamine release in both areas, selectively antagonized (+)SKF 10,047-induced dopamine release in the nucleus accumbens. Haloperidol by itself increased dopamine release in both areas and these effects were additive with those induced by (+)SKF 10,047. PMID- 1499655 TI - Dopamine release and dopaminergic inhibition of acetylcholine release in rat striatal slices after nigro-striatal hemitransection and parenteral ganglioside administration. AB - Hemitransection of the nigro-striatal bundle in adult rats reduced [3H]dopamine ([3H]DA) uptake into striatal slices from the lesioned side to about 20% of that in the contralateral side 5 days after surgery. Spontaneous recovery of [3H]DA uptake was observed at days 8 and 15 post-lesion (42 and 67% of the unoperated side, respectively). After a short treatment (3 days) with the GM1 ganglioside inner ester (AGF2, 30 mg/kg i.p., daily, starting on day 2 after surgery) [3H]DA uptake amounted to 52% of that in the unoperated side. The electrically evoked fractional overflow of [3H]DA was increased by 500% in slices prepared from the lesioned side 5 days after injury, largely due to the reduced re-uptake by the DA axon terminals. The increase on day 5 was only about 350% in AGF2-treated animals. The DA D2 receptor antagonist, (-)-sulpiride, potentiated the stimulus evoked overflow of [14C]acetylcholine in slices from the unoperated side prelabelled with [14C]choline. The effect of (-)-sulpiride was much reduced (by about 80%) in the lesioned striata at days 5 and 8 after surgery. Partial recovery was seen at day 15. The lesion did not modify the (-)-sulpiride effect in animals treated with AGF2 from the 2nd to the 5th day post-lesion. Thus early ganglioside administration slows the loss of endogenous dopaminergic control of acetylcholine release caused by partial hemitransection of the nigro-striatal bundle. PMID- 1499656 TI - Mechanisms involved in the hyperglycemic effect of the 5-HT1C/5-HT2 receptor agonist, DOI. AB - Previous experiments have indicated that 5-HT2 receptors and catecholaminergic systems mediate the rise in plasma glucose levels elicited by acute administration of the 5-HT1c/5-HT2 receptor agonist, 1-(2,5-dimethoxy-4 iodophenyl)-2-aminopropane (DOI). On this basis, we investigated the location of these serotonin receptors and the nature of this catecholaminergic involvement. Administration of DOI (0.4 mg/kg i.v.) to conscious rats (bearing jugular catheters) elicited a rapid rise in plasma glucose which was associated with a decreased insulin response to a glucose bolus (300 mg/kg i.v.). Pretreatment with the peripherally acting 5-HT1c/5-HT2 receptor antagonist, BW 501C67 (0.5 mg/kg i.v. 10 min beforehand) prevented the rise in plasma glucose triggered by the peripherally acting 5-HT1c/5-HT2 receptor agonist, alpha-methyl-5-HT (0.75 mg/kg i.v.), but amplified the rise elicited by DOI. Pretreatment with chlorisondamine (1 mg/kg i.v. 10 min beforehand) or adrenalectomy 20 h beforehand prevented the DOI-induced hyperglycemia. On the other hand, pretreatment with dexamethasone (0.35 mg/kg s.c. 2 h and 20 min beforehand) did not affect the DOI-induced hyperglycemia. It is concluded that the hyperglycemic effect of DOI administration is mediated by centrally located 5-HT2 receptors and, in turn, adrenal epinephrine release. PMID- 1499657 TI - Characterization of muscarinic receptors mediating vasodilation in guinea-pig ileum submucosal arterioles by the use of computer-assisted videomicroscopy. AB - Muscarinic receptors of resistance vessels (submucosal arterioles, outside diameter 50-75 microns) from the guinea-pig small intestine were investigated in vitro using a computer-assisted videomicroscopy system (Diamtrak). The muscarinic receptor which mediates vasodilation of precontracted [U-46619 (300 nM) or (-) noradrenaline (10 microM)] arterioles was characterized with several muscarinic agonists and subtype-selective antagonists. The following agonists all produced equivalent maximum vasodilation (given in rank order of potency): acetylcholine = arecaidine propargyl ester (APE) greater than oxotremorine = (+/-)-muscarine = (+/-)-methacholine greater than carbachol greater than 4-[[N-(4 chlorophenyl)carbamoyl]oxy]-2-butynyltrimethylammonium iodide (4-Cl-McN-A-343). 4 [[N-(3-Chlorophenyl)-carbamoyl]oxy]-2-butynyltrimethylammonium chloride (McN-A 343) and N-ethyl-guvacine propargyl ester (NEN-APE) produced minimal or no arteriolar vasodilation. The muscarinic antagonists pirenzepine, (+-)-5,11 dihydro-11-[[[2-[2-((dipropylamino)methyl)-1-piperidinyl] ethyl]amino]-carbonyl] 6H-pyrido(2,3-b)(1,4)-benzodiazepin-6-one (AF-DX 384), 11-[[4-[4 (diethylamino)butyl]-1-piperidinyl]acetyl]-5,11-dihydro- 6H-pyrido(2,3-b)(1,4) benzodiazepin-6-one (AQ-RA 741), p-fluorohexahydro-sila-difenidol (p-F-HHSiD), 4 diphenylacetoxy-N-methylpiperidine methiodide (4-DAMP) and (R)- and (S)-hexahydro difenidol [(R)-HHD, (S)-HHD] shifted the muscarine, methacholine or carbachol dose-response curve to the right in a competitive manner. Schild analysis of the data yielded pA2 values for pirenzepine (6.74/6.9), AF-DX 384 (6.72), AQ-RA 741 (6.58), p-F-HHSiD (7.53/7.57), 4-DAMP (9.06), (R)-HHD (7.88/8.32) and (S)-HHD (5.52/5.88). Thus, it can be concluded that submucosal arterioles possess only the M3 functional muscarinic receptor, the activation of which causes blood vessel dilation.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1499658 TI - Excitatory effects of adenosine 5'-triphosphate on rat locus coeruleus neurones. AB - Pontine slices of the rat brain were used for extracellular recording of the frequency of spontaneous action potentials of locus coeruleus (LC) neurones. In the absence of 8-cyclopentyl-1,3-dipropylxanthine (DPCPX), alpha,beta methyleneadenosine 5'-triphosphate (alpha,beta-meATP; 0.3-30 mumol/l) and 2 methylthio ATP (0.3-100 mumol/l), but not ATP (1-100 mumol/l) increased the firing rate. In the presence of DPCPX 0.1 mumol/l, all three purinoceptor agonists were active, the potency order being alpha,beta-meATP greater than 2 methylthio ATP = ATP. Preincubation of the slices with tetrodotoxin (TTX) 0.5 mumol/l decreased the spike discharge but did not alter the percent facilitatory effect of alpha,beta-meATP 30 mumol/l. There was no desensitization to alpha,beta meATP 10 mumol/l on repeated or continuous application. Suramin 100 mumol/l selectively depressed the effect of alpha,beta-meATP 30 mumol/l without interfering with the effect of equiactive concentrations (10-100 mumol/l) of glutamic acid. The concentration-response curve of alpha,beta-meATP was shifted in a parallel manner to the right by suramin 10 mumol/l. While DPCPX 0.1 mumol/l facilitated firing, suramin 100 mumol/l did not change it. In conclusion, LC neurones may possess P2-purinoceptors of an unidentified type, which share some P2x characteristics. PMID- 1499659 TI - Naltrindole retards tolerance development to morphine-induced effects on EEG and EEG power spectra. AB - In the present study, EEG and EEG power spectra were used to assess the effects of naltrindole, a selective delta opioid antagonist, on the development of tolerance to morphine. Adult female Sprague-Dawley rats were implanted with cortical EEG electrodes and permanent indwelling i.c.v. and i.v. cannulas. Twice daily for 7 days, rats were pretreated with either i.c.v. naltrindole (20 nmol) or i.c.v. water, 20 min before i.v. morphine (10 mg/kg) injections. The treatments produced EEG slow-wave bursts and associated behavioral stupor. The amount and duration of these effects decreased less rapidly over the 7 days in the naltrindole-pretreated rats than in the water-pretreated rats. I.c.v. naltrindole pretreatment also prevented significant decreases in latency to onset of slow-wave sleep that were seen in the i.c.v. water-pretreated group. EEG data were further analyzed on a Pathfinder II computer. The development of tolerance was reflected by decreases in the total absolute EEG spectral power (1-50 Hz) over the 7-day period. Rats that were pretreated with i.c.v. naltrindole (20 nmol) did not display a significant decrease in total absolute EEG spectral power by the 7th day, as did the i.c.v. water-pretreated group. Furthermore, significant differences were seen for complexity, mobility, and edge frequency between the two pretreatment groups. A delayed qualitative change in the EEG power spectra was also observed in rats pretreated with i.c.v. naltrindole. On day 1, EEG slow-wave bursts were associated with increases in EEG spectral power over the 1-10 Hz range.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1499660 TI - Effects of nor-binaltorphimine on the development of analgesic tolerance to and physical dependence on morphine. AB - The effects of a highly selective kappa antagonist, nor-binaltorphimine (nor BNI), on the development of tolerance to morphine analgesia and physical dependence on morphine were examined. Pretreatment with nor-BNI (5 mg/kg s.c.) 2 h prior to injection of morphine or a selective kappa agonist, U-50,488H, significantly antagonized the analgesic effect of U-50,488H, but not morphine analgesia in mice. The development of tolerance to morphine analgesia was significantly potentiated by pretreatment of mice with nor-BNI 2 h prior to morphine treatment during chronic morphine treatment for 5 days. Additionally, the pretreatment with nor-BNI during chronic treatment with the high dose of morphine for 5 days significantly potentiated the naloxone-induced body weight loss in morphine-dependent mice and rats. These findings suggest that inactivation of the kappa opioid system may potentiate the development of tolerance to morphine analgesia in mice and may aggravate the naloxone precipitated body weight loss in morphine-dependent mice and rats. PMID- 1499661 TI - Effects of cocaine and its quaternary derivative cocaine methiodide on cardiovascular function in squirrel monkeys. AB - The effects of cocaine and its quaternary derivative cocaine methiodide, which does not cross the blood-brain barrier, were studied on cardiovascular function in squirrel monkeys. In conscious monkeys, cocaine produced clear dose-dependent increases in blood pressure and heart rate, while cocaine methiodide did not. Both cocaine and cocaine methiodide enhanced the effects of norepinephrine in anesthetized animals, suggesting that both inhibit neuronal uptake of norepinephrine; cocaine was approximately 30 times more potent than cocaine methiodide. In anesthetized monkeys both cocaine and cocaine methiodide produced small, short duration pressor effects, although cocaine was at least 10 times more potent than cocaine methiodide. Cocaine's effects in anesthetized animals were clearly blunted in comparison to its effects in conscious animals. These effects of cocaine on blood pressure occurred at doses lower than those required to enhance norepinephrine's effects, indicating that the norepinephrine uptake blocking effects of the drugs cannot fully account for their cardiovascular effects. The greatly enhanced effect of cocaine in conscious animals and the finding that cocaine methiodide had little effect in conscious animals indicates that central mechanisms are involved in the effects of cocaine on cardiovascular function in conscious animals. PMID- 1499662 TI - Effects of methoxamine and barium on 45Ca2+ fluxes in the rat vas deferens. AB - The aim of this study was to determine whether methoxamine and barium stimulate 45Ca2+ uptake or efflux in the rat vas deferens in a manner that correlates with their contractile activity, and whether 45Ca2+ movements are inhibited by verapamil or nifedipine. Basal La(3+)-resistant (cellular) 45Ca2+ uptake was significantly greater in the epididymal half (791 +/- 27 nmol g-1) than in the prostatic half (654 +/- 14 nmol g-1) of the rat vas deferens and was unaffected by verapamil (61 microM) or nifedipine (14 microM). Methoxamine (8 microM) was without effect on 45Ca2+ uptake in either half but BaCl2 (1 mM) increased 45Ca2+ uptake by 31% in the prostatic half and by 22% in the epididymal half. The barium induced increases in 45Ca2+ uptake were markedly reduced or abolished by verapamil (2 microM) or nifedipine (0.3 microM), which at these concentrations have no effect on the rhythmic contractions but abolish the initial small phasic contraction induced by barium. The basal rate of 45Ca2+ efflux from the intact vas deferens (into Ca2+ containing Krebs-Henseleit solution or into Ca-free Krebs Henseleit solution +/- EGTA 0.05 mM) was not affected by verapamil (61 microM) or nifedipine (14 microM). Methoxamine (8 microM) produced a marked, transient and reversible increase in 45Ca2+ efflux into 2.5 mM CaCl2 Krebs-Henseleit in 50% of the intact vasa deferentia examined which was augmented by verapamil (61 microM). BaCl2 (1 mM) produced a small increase in 45Ca2+ efflux into Ca(2+)-containing and Ca(2+)-free Krebs-Henseleit solutions from some intact vasa deferentia and this was not inhibited by nifedipine (14 microM).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1499663 TI - Prolactin induces growth-related gene expression in rat aortic smooth muscle in vivo. AB - We examined the effects of in vivo administration of prolactin on growth-related gene expression in aorta. Optimal mRNA expression for both the proto-oncogene, c myc and ornithine decarboxylase occurred at 22 mg/kg prolactin. For c-myc, this was seen as early as 15 min. Prolactin-induced ornithine decarboxylase mRNA expression began at 1 h. The results confirm work showing induction of these genes by prolactin in tissues where it is mitogenic and supports a role for prolactin in the trophic response of vascular smooth muscle. PMID- 1499665 TI - Transferable antibiotic resistance among thermotolerant coliforms from rural drinking water in India. AB - A total of 231 thermotolerant coliforms was isolated from rural drinking water from four states of India. Of these, 220 isolates were resistant to ampicillin, chloramphemicol, streptomycin and tetracycline. Multiple (MAR), double and single antibiotic resistances were observed in 31.4, 48.6 and 13.7% of the isolates, respectively. Out of 177 antibiotic-resistant isolates examined for transmissibility, only 15.3% were able to transfer their resistances to Escherichia coli K-12 recipient. The resistances were transferred by 32.5% of MAR, 21.9% of double resistant and 7.6% of single resistant isolates. Ampicillin resistance was transferable in 14.69% strains while resistances for the rest of the antibiotics were transferable in less than 4% strains. MAR strains of E. coli and Klebsiella sp. showed highest levels of R-plasmid transfer. PMID- 1499664 TI - Giardia--diagnosis, clinical course and epidemiology. A review. AB - Infection with giardia may be associated with significant ill-health and while the reported incidence of infection is increasing in the United Kingdom, the true prevalence of infection and extent of morbidity due to this organism is unknown. Diagnosis is made difficult by non-specificity of symptoms and low sensitivity of traditional diagnostic techniques. Immunological methods of diagnosis hold promise for the future, but in the meantime, more routine testing by laboratories and multiple faecal testing by clinicians may prevent unnecessary morbidity. The late summer/autumn peak in reported infection is difficult to explain while the age distribution is typical of an organism which is spread faeco-orally. The importance of potable water supplies as a source of infection in this country is not clear, nor is the role of zoonotic spread. The apparent susceptibility to infection of certain population groups requires further exploration as does the role of the asymptomatically infected in transmission. PMID- 1499666 TI - The ability of airborne Klebsiella pneumoniae to colonize mouse lungs. AB - A strain of Klebsiella pneumoniae was aerosolized and its survival in air at different relative humidities was studied. Survival was dependent upon relative humidity and aerosols were most stable during storage at a relative humidity of 60%. Mice were exposed to aerosols of K. pneumoniae produced at this humidity and lung samples taken at timed intervals after exposure. Fifteen strains of K. pneumoniae were tested for their ability to colonize mice, but only five were detectable in mouse lungs 7 days after exposure. Three of these strains persisted without an increase in bacterial numbers, regardless of the initial inoculum used. Two strains of K. pneumoniae, designated strains 15 and 16, persisted in a similar manner when used at a low dose; however, when the dose received per lung was increased there was a rapid multiplication of bacteria in the lungs. PMID- 1499667 TI - Intestinal spirochaetes colonizing aborigines from communities in the remote north of Western Australia. AB - Intestinal spirochaetal bacteria were isolated from 59 of 181 (32.6%) faecal samples obtained from Aboriginal children and a few adults living in communities in the Kimberley region in the north of Western Australia. Colonization was more common in young Aborigines between 2 and 18 years of age than it was in adults, or in babies and children less than 2 years of age. Three of 22 Aboriginal children who were sampled on two consecutive years were colonized on both occasions. None of four other children were found to be consistently colonized with the bacteria when sampled on three sequential years, but three were positive on two consecutive visits and the other child was positive on the first and third sampling. Most Aboriginal children had abnormal or watery stools, and both abnormal and watery stool samples were significantly more likely to contain spirochaetes than were normal samples. However, it was not possible to prove that the spirochaetes were the cause of the diarrhoea. In contrast, spirochaetes were only recovered from 8 of 695 (1.2%) faecal samples that were obtained from other mainly non-Aboriginal children and adults in Western Australia or the Northern Territory of Australia, even though most of these individuals were suffering from gastrointestinal disturbances. PMID- 1499668 TI - Vector potential of hospital houseflies with special reference to Klebsiella species. AB - The vector potential of houseflies (Musca domestica) for Klebsiella spp. was investigated. Klebsiella spp. (mostly Klebsiella pneumoniae) were isolated from 36.7% of hospital flies and 28.1% of infected wounds of patients. Antibiograms of Klebsiella spp. showed that 82.0% of isolates from hospital flies and 96.3% from infected wounds were resistant to four or more commonly used antimicrobials. In contrast, from the control group, only 8.7% klebsiella isolates showed similar antimicrobial resistance pattern (P less than 0.001). Similar strains of Klebsiella spp. were encountered among patients and hospital houseflies. The results indicate that flies in the hospital environs are potential vectors of hospital resistant strains of Klebsiella spp. PMID- 1499669 TI - Short-term predictions of HIV prevalence and AIDS incidence. AB - Reports of AIDS cases in Amsterdam up to February 1990 were used to make predictions of future cases up to 1993. Two published methods were applied, which make extrapolations from current cases and simultaneously estimate the extent of delay in reporting. The choice of the exact model greatly influenced the predictions, as did predictions for distinct transmission groups. We present results for the homo/bisexual male group, and the total population of Amsterdam. The AIDS case predictions are used to predict the HIV prevalence using the ratio of HIV prevalence to AIDS incidence and through 'back calculation'. We suggest that the ratio is a simple technique that may be used to estimate HIV prevalence. The estimated number of cumulative HIV infected homo/bisexual males in Amsterdam in January 1990 was between 2100 and 4100 in a total of 2200-4600 infected people. PMID- 1499671 TI - Mycobacterium bovis in England and Wales: past, present and future. AB - This report reviews the literature concerning tuberculosis resulting from infection with Mycobacterium bovis in man and cattle and summarises data derived from surveillance of M. bovis in England and Wales from 1986 to 1990. Of the 228 isolates of M. bovis examined in this period, 122 (53%) were from patients aged over 60 years and are largely the result of reactivation of infection acquired prior to the institution of control measures. However, eight isolates (3.5%) were from patients aged less than 30 years. The potential sources for these presumed primary infections include the few remaining cattle infected with M. bovis or infectious human cases in the United Kingdom. However, infections acquired abroad, especially in immigrants, may account for some of these cases. Outbreaks of tuberculosis due to M. bovis continue to occur in cattle. Wild animals, particularly badgers, have been implicated as reservoirs of the infection. However, man may also prove to be an important reservoir of M. bovis for cattle as well as humans. PMID- 1499670 TI - An outbreak of hepatitis A in Gloucester, UK. AB - During an outbreak of hepatitis A that occurred in Gloucester, UK between September 1989 and January 1991, 162 clinical cases were identified through notifications and laboratory reports, a monthly attack rate of 1.05 per 10,000 residents. The highest attack rate was seen in 5-14-year-olds. There were significant correlations between hepatitis A attack rates in the electoral wards of Gloucester and with the Jarman UPA 8 scores for the wards and with overcrowding, unemployment, under 5-year-olds and ethnic minority. The use of human normal immune globulin prophylaxis (HNIG) for household contacts was unsuccessful in ending the outbreak, partly because only one third of cases reported a household contact with recent hepatitis A. Our experience does not support the use of HNIG in stopping community-wide outbreaks of hepatitis A. Two public health campaigns were mounted during the outbreak; both were followed by a fall in the number of cases. Greater priority should be given to the implementation and evaluation of public health campaigns in future community-wide outbreaks of hepatitis A. PMID- 1499672 TI - Legionella pneumophila in residential water supplies: environmental surveillance with clinical assessment for Legionnaires' disease. AB - Although cases of community-acquired Legionnaires' disease have been epidemiologically linked to residential water supplies, the risk of acquiring Legionnaires' disease from exposure to Legionella pneumophila in residential water systems is uncertain. The residential water supplies of 218 members of the American Legion in six different geographical areas in Pittsburgh were cultured for L. pneumophila. Residents of the homes provided a recent medical history and a blood sample for detection of antibodies to legionella. A urine sample for legionella urinary antigen testing was also requested from individuals residing in legionella-positive homes and individuals with a positive antibody test. Six percent (14/218) of the homes yielded L. pneumophila (range within six areas 0 22%). Lower hot water tank temperature was significantly associated with legionella positivity (P less than 0.01). Analysis of water samples for mineral content showed no association between legionella positivity and concentrations of calcium and magnesium. Water samples from the area where 22% of the homes surveyed were positive for legionella had a higher iron content than water samples from the other areas tested. None of the individuals residing in legionella-positive homes showed elevated antibody titres to legionella or the presence of legionella antigen in urine. For the immunocompetent hosts, the risk of contracting Legionnaires' disease from exposure to contaminated household water supplies in the Pittsburgh area appears to be low. PMID- 1499673 TI - Restriction endonuclease fingerprinting of genomic DNA of Staphylococcus species of bovine origin. AB - Fifty-one staphylococcal isolates from mammary secretions of cows with subclinical mastitis were examined by antibiograms and DNA restriction endonuclease fingerprinting (REF). DNA REF differentiated closely related strains of each species isolated from mammary secretions of different mammary glands of the same cow and from the same mammary gland at different periods of the lactation cycle. In addition, REF analysis provided evidence concerning persistence of infection in the same or different mammary gland over different periods of the lactation cycle, and occurrence of infection with similar and dissimilar strains of each Staphylococcus species. Antibiograms were of limited value in differentiating closely related strains. The ease by which REF analysis can be performed together with the reproducibility and clarity of REF patterns suggest that this technique is useful for differentiating closely related and unrelated strains of Staphylococcus species isolated from bovine mammary secretions. PMID- 1499674 TI - Helicobacter pylori, musings from the epidemiologic armchair. AB - The literature on Helicobacter pylori has become enormous, but the epidemiology of the infection remains an enigma. Guided by epidemiologic principles we have tried to interpret the available data on the epidemiologic aspects of H. pylori. We conclude that conflicting results on familial clustering and seroprevalence curves might have logical explanations. However, the exact way this organism spreads among humans remains to be solved. PMID- 1499675 TI - A study into the mechanism of the Crystal Violet reaction in Staphylococcus aureus. AB - The mechanism of the Crystal Violet (CV) reaction, a trait which has been related to biotype, source and pathogenicity in Staphylococcus aureus, was investigated in agar and broth studies. White reactions could be converted to purple and vice versa by altering the incubation conditions on agar. Broth reactions examined macroscopically and by spectrophotometry revealed that both white and purple human biotype strains take up CV but the former then progressively modify the dye more quickly than the latter. A cell-associated product of CV was detected in white and purple strains by reverse-phase thin-layer chromatography of methanol extracts. White strains appear to produce a second additional product from CV. The white reaction was not inhibited by chloramphenicol or azide but did depend on viable cells with a nutrient source. CV MICs and MBCs for 10 white and 10 purple reactors showed no gross differences in susceptibility, while a standardized assay for the rate of CV modifying activity (52 strains) demonstrated that the two categories comprise discrete populations which alter CV at different rates. Although most white strains belong to either or both of phage typing groups V and II, purple strains with this pattern of susceptibility and white strains without it both occur. The capacity to modify CV slowly or rapidly appears to subdivide human biotype strains independently of their phage group and is associated in the former case with their capacity to produce hospital-acquired and invasive infections. PMID- 1499676 TI - The epidemiology of ciprofloxacin resistance in coagulase-negative staphylococci in CAPD patients. AB - Ciprofloxacin was used as empirical therapy for peritonitis in patients receiving continuous ambulatory peritoneal dialysis (CAPD) for 26 months, providing an opportunity to study the epidemiology of ciprofloxacin resistance amongst coagulase-negative staphylococci (CNS). Swabs were collected from the CAPD patients, staff, and clinic environment before, during and after the time this antibiotic was prescribed. Clinical isolates were also studied, and records kept of patient hospital attendance. Ciprofloxacin-resistant staphylococci were typed by antibiogram, biotype, plasmid profile, SDS-PAGE, and immunoblotting. No resistant strains were detected before the use of ciprofloxacin. During its use 30% of patients became skin carriers, and resistant strains caused 8% of peritonitis episodes in 7% of patients (38% of carriers). Resistant strains were isolated from the environment, but never from attending members of staff. A total of 208 resistant isolates with MIC's between 8 and 128 mg/l was collected and identified as Staphylococcus epidermidis or S. haemolyticus. Sixteen strain types were distinguished. There was epidemiological evidence for selection of resistant strains derived from the host commensal flora and also for cross-colonization, and cross-infection. Carriage of resistant strains fell to 15% of patients, 6 months after the use of ciprofloxacin had ceased. PMID- 1499677 TI - Comparative aspects of age-related plasticity in the adult nervous system. PMID- 1499678 TI - Introductory remarks: age-induced plasticity in nervous systems of diverse species. PMID- 1499679 TI - Neuron addition in the postmetamorphic frog. AB - Neuron number among somatic motoneurons, sensory neurons, and sympathetic postganglionic neurons that innervate the hindlimb was correlated with body length in the bullfrog, Rana catesbeiana. Two to three times more dorsal root and sympathetic ganglion neurons are found in the largest than the smallest specimens. Hindlimb motoneurons show a 20% increase in number, but this increase is restricted to the caudal third of the motor pool. Within this region, 60% more motoneurons are found among the largest frogs. Cell division does not appear to be the mechanism of neuron addition. Instead, we propose that a pool of undifferentiated neurons mature to maintain functional capabilities as the animal increases in size. PMID- 1499680 TI - Aging and the neurocytoskeleton. AB - It has been often demonstrated that during senescence some neurons undergo atrophic changes while others add new processes and terminals. Because microtubules form a substantial component of the dendritic and axonal cytoskeleton, we have studied the amount of tubulin and acetylated alpha-tubulin in three young (6 months) and three old (24 months) rats (Fischer 344). We have used sodium dodecyl sulfate (SDS) extracts of brain homogenates and Triton solubilized fractionated brain homogenates. With the first method we did not detect any age-related differences in total brain protein, total tubulin, or in relative amounts of acetylated alpha-tubulin. With the second method, we have observed a small systematic increase in relative amount of acetylated alpha tubulin in the Ca2+/cold insoluble fraction. These results are similar to those reported in the literature, and they indicate a possible alteration in the cytoskeletal dynamics. PMID- 1499681 TI - Proceedings of a conference on correlations of aging and space effects on biosystems. PMID- 1499682 TI - Insect systems for the study of programmed neuronal death. AB - In the moth Manduca sexta and the fly Drosophila melanogaster, the emergence of the adult is followed by a period of neuronal death. The steroid hormones, the ecdysteroids, are involved in two aspects of this death. Ecdysteroid action early in metamorphosis is somehow essential for fixing the fates of the neurons that will die. The actual triggering of their death, however, occurs a few weeks later and requires the withdrawal of the steroid and, at least in some cases, a trans synaptic signal. These "execution" events involve both RNA and protein synthesis and result in the onset of degeneration about 10 h later. The early "decision" of a neuron to opt for the degeneration fate is associated with an altered pattern of ecdysteroid receptor expression. A model is presented to relate how the levels of steroid receptors may be related to the activation of death-related genes. PMID- 1499683 TI - Calcium as sculptor and destroyer of neural circuitry. AB - This paper examines the hypothesis that intracellular calcium plays guiding roles in the formation and adaptive modification of neural circuits in development and adult plasticity and that imbalances in calcium regulation lead to the degeneration of neural circuits in aging and disease. The neuronal growth cone is the motile structure largely responsible for the generation of neuroarchitecture. Studies of developing neurons in culture demonstrated that environmental signals believed to play key roles in neural development (i.e., neurotransmitters and growth factors) regulate growth cones by altering neuronal calcium-regulating systems. Different components of neurite outgrowth (i.e., neurite elongation and growth cone motility) are based upon different cytoskeletal systems (microtubules and microfilaments) which are differentially affected by calcium. In addition, cytoskeleton-associated proteins such as tau and microtubule-associated protein 2 (MAP2) are likely candidates for regulation by calcium. "Natural" neuronal death in development may occur as the result of growth factor deficiency or excess excitatory activity leading to sustained elevations in intracellular calcium levels. With aging and in disease, a loss of calcium homeostasis may underlie the aberrant neurodegeneration that occurs. For example, neurons subjected to conditions (e.g., glutamate and beta-amyloid) that cause sustained rises in intracellular calcium exhibit changes in the cytoskeleton similar to those seen in neurofibrillary tangles of Alzheimer's disease and related disorders. Taken together, the data suggest that cellular systems for calcium homeostasis are integral to both the adaptive and aberrant neuroarchitectural changes that occur throughout the lifespan of the nervous system. PMID- 1499684 TI - Age-dependent alterations of synaptic performance and plasticity in crustacean motor systems. AB - Age-related changes in synaptic performance and plasticity are surveyed in crustacean neuromuscular systems. These systems are functionally differentiated into phasic and tonic types, with different attributes of synaptic function and plasticity. Conversion of phasic neuromuscular junctions to a more phasic phenotype can be brought about by altering the activity of selected neurons. This type of plasticity disappears in older animals in some motor neurons, but is retained in others. Developmental programs set constraints on the age-dependent modifications of plasticity. Crustacean motor neurons are often characterized by great longevity, with progressive addition of new branches and synapses to keep up with growth of innervated muscle cells. Certain age-related compensatory mechanisms found in neuromuscular junctions of other species may not be required in crustaceans. PMID- 1499685 TI - Age-related remodeling of lobster neuromuscular terminals. AB - Multiterminal innervation of a lobster limb muscle by an identified excitor motoneuron was examined during primary development and adult growth. To keep pace with the growth in the target muscle, axonal branches proliferate by sprouting from synaptic terminals; an increasingly complex branching pattern results. Neuromuscular synapses multiply in number, enlarge in size, and become perforated. Concomitantly, synapses tend to appear on the more distal axonal branches and to disappear on more proximal branches, providing for continual remodeling of multiterminal innervation. This plasticity in an identified motoneuron occurs over a long life span of several decades. PMID- 1499686 TI - Mechanisms in senescence: some thoughts in April 1990. PMID- 1499688 TI - Differences in aging in two neural pathways: proposed explanations from the nervous system of Aplysia. AB - A basic question in studies of the neurobiology of aging is to what extent age related changes are genetically preprogrammed or epigenetically mediated. Our approach to this question is to compare the effect of age on two neural pathways in the marine mollusc, Aplysia. The advantage of Aplysia as a model of neural aging is that age-sensitive properties in the pathways can be studied at the behavioral, physiological, and morphological levels. The two pathways we are investigating respond differently to aging; a comparison of the pathways' properties provides a means of distinguishing the effect of age from other variables in the same animal. Age effects are expressed in the gill withdrawal reflex pathway at the three levels but are minimal in the gill respiratory pathway. The behavioral and physiological expressions of the reflex pathway are weakened in old animals (250 days of age and older) when compared to those in mature ones (ca. 160 days of age). The major differences between the two pathways are: (1) the reflex pathway appears to exhibit more plasticity than the respiratory pathway, and (2) the level of use of the respiratory pathway is more regular and frequent than that of the reflex pathway. The greater plasticity intrinsic to the reflex pathway and its level of use may well be the characteristics upon which age-related changes depend. An interplay between genetic and epigenetic factors is suggested to help explain the differential aging in the two pathways. PMID- 1499687 TI - Compensatory plasticity of aging at the neuromuscular junction. AB - Several age-related phenomena observed at the neuromuscular junction (NMJ) can be viewed as adaptations to cellular deficits. These compensatory mechanisms, which maintain functional and morphologic integrity, are those present in the adult animal. In the study of compensatory mechanisms with age, the choice of an appropriate animal model is important. Three adaptations are discussed: maintenance or increase of transmitter release despite reduced supply of synaptic vesicles; functional reactive sprouting after partial denervation despite reduced axonal transport; and maintenance of nerve terminal integrity in the face of increased outgrowth and retraction. In all cases, successful adaptation in old animals is obtained at the expense of a more fragile system. Either the compensations themselves or the resulting vulnerability may alter the reactions of the aging nervous system to changes in external and internal milieu. PMID- 1499689 TI - Hormonally-induced alterations in synaptic organization in the adult nervous system. AB - In recent years, there is growing evidence that vertebrate neural circuits involved in reproduction retain a considerable amount of plasticity in adulthood. Gonadal steroid hormones cause dramatic changes in the synaptic organization of these circuits to regulate the expression of reproductive behavior. Two model systems are described to illustrate such changes: the neural system controlling song in passerine birds, and the spinal nucleus of the bulbocavernosus system in the rat spinal cord. PMID- 1499690 TI - Neuronal migration on laminin involves neuronal contact formation followed by nuclear movement inside a preformed process. AB - Neuronal migration was investigated in rodent cerebellum in vitro and in vivo. Time-lapse video recording showed that cultured neurons migrated on laminin by first extending neurites that formed contacts with other neurons. This was followed by movement of the cell nucleus inside the preformed process. No guidance cues other than laminin were required. When the rodent premigratory (E18 P0) cerebellum was examined by immunocytochemistry, the radial glial cells were found to have extracellular punctate deposits of laminin along their fibers. Such punctate deposits of laminin were more numerous in the premigratory cerebellum than during the peak of neuronal migration (e.g., at 7-10 days postnatally). At the same time (E18-P0) L1 antigen- and neurofilament-positive, presumably granule cell processes extend radially from the external granule cell layer (EGL). These results imply that neuronal migration on laminin in vitro involves neuronal contact formation followed by nuclear movement inside a preformed process. That this mode of neuronal migration may occur in vivo is indicated by the fact that L1 antigen- and neurofilament-positive "pioneer neurites" colocalize with the punctate deposits of laminin deposited along the radial glial processes in the premigratory EGL. Taken together these results imply that the established glial dependency of the granule cell migration may in fact be dependency of the granule cells and their pioneer neurites on the punctate deposits of laminin produced and laid down by the glial cells. PMID- 1499691 TI - Persistent innervation of the rat neocortex by basal forebrain cholinergic neurons despite the massive reduction of cortical target neurons. I. Morphometric analysis. AB - In Alzheimer's disease, a characteristic neurochemical abnormality is the loss of cholinergic enzymes in the neocortex, reflecting the degeneration of basal forebrain neurons responsible for cholinergic innervation of the neocortex. It is hypothesized that basal forebrain neuronal degeneration results from a reduction in the level of trophic factors synthesized by neurons in the target regions of cholinergic projections. Data from a large number of animal lesioning studies tend to support this theory; however, most of these lesions also induce widespread, nonspecific injury responses in the CNS. To directly test the dependence of basal forebrain cholinergic neurons on target-derived neurotrophic support, pregnant Sprague-Dawley rats were injected with moderate doses of methylazoxymethanol acetate (MAM) on Gestational Days 14 and 15. Extensive morphometric analysis of offspring reveals that the prenatal administration of MAM during this period of neurogenesis results in the ablation of 40-70% of cortical neurons, without significant effects on the hippocampus or the genesis of basal forebrain cholinergic neurons. Examination of MAM-treated animals at several ages reveals no significant differences in neuronal density of cholinergic neurons as compared to controls. Extensive analysis of animal brains at several time points has failed to reveal any evidence of classical injury responses which might be responsible for preservation of basal forebrain neurons. These results contradict the theory that mature basal forebrain cholinergic neurons are critically dependent on the availability of target-derived neurotrophic factors and are therefore unlikely to be the major etiological factor in basal forebrain neuronal degeneration characteristic of Alzheimer's disease. PMID- 1499692 TI - Changes in brain polyamine levels following head injury. AB - The changes in polyamines levels in the brain after closed head injury were studied in rats. At 1 and 15 min, 24 and 48 h after closed head injury cortical tissue from the site of injury, from the contralateral region, and from remote areas were taken. The levels of the diamine putrescine and the polyamines spermine and spermidine were assayed by thin layer liquid chromatography of their dansyl derivatives. Head injury induced a significant increase in putrescine at 48 h at the site of injury and in the frontal lobe of the injured hemisphere, respectively. In the contralateral hemisphere only minor changes in putrescine were found. Spermine and spermidine showed minor changes at that time course. We have previously shown that at 24-48 h after injury, severe edema is found at the site injury. In order to study the role of putrescine in edema formation in this model we treated the traumatized rats with alpha-difluoromethyl-ornithine (DFMO), an inhibitor of ornithine-decarboxylase, the rate limiting enzyme in putrescine biosynthesis. This drug did not affect the level of edema 4 or 48 h after injury although it abolished the increase in putrescine. The effect of DFMO on blood brain barrier function was studied, using Evans blue extravasation, at the early post-traumatic period (15 min-4 h), where a massive amount of dye is taken up by traumatized brain. No changes in the amount of dye extracted was found after DFMO treatment. On the other hand, DFMO had a beneficial effect on the neurological outcome, as evaluated by a set of clinical criteria.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1499693 TI - Activity of ornithine decarboxylase and S-adenosylmethionine decarboxylase in transient cerebral ischemia: relationship to the duration of vascular occlusion. AB - Mongolian gerbils were anesthetized with halothane and forebrain ischemia was induced by occluding both common carotid arteries. After 2, 4, 6, 8, or 10 min of vascular occlusion clips were removed and animals allowed to recover for 8 or 24 h. At the end of the experiments animals were reanesthetized and their brains frozen in situ. Tissue samples were taken from the cerebral cortex, striatum, hippocampus, and thalamus for determination of ornithine decarboxylase (ODC) and S-adenosylmethionine decarboxylase (SAMDC) activity by measurement of the release of 14CO2 from [14C]ornithine and S-[14C]adenosylmethionine, respectively. A transient increase in ODC activity was found after 8 h of recirculation following cerebral ischemia in all brain structures studied. ODC activity was significantly increased after 8 h of recirculation in the hippocampus of animals subjected to 4 min of ischemia, in the cortex and striatum after 6 min of ischemia, and in the thalamus after 8 min of vascular occlusion. ODC activity had already reached a plateau in the hippocampus after 4 min of vascular occlusion and in the cortex, striatum, and thalamus after 8 min, since there is no further increase in activity even after 10 min of ischemia. After cerebral ischemia and 24 h of recirculation ODC activity returned to control levels throughout the forebrain regardless of the duration of ischemia. SAMDC activity was significantly reduced after 8 h of recirculation following 4 to 10 min of ischemia in the cortex and 8 min of ischemia in the striatum.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1499694 TI - Analgesic and aversive effects of naloxone in BALB/c mice. AB - Opioid antagonists have been shown to produce dose-dependent analgesia in the formalin test in BALB/c mice. In light of this paradoxical finding, the motivational-affective property of naloxone was examined in BALB/c mice. Naloxone produced a conditioned place aversion at doses which were also found to produce analgesia in the formalin test (1 and 10 mg/kg). In addition, the analgesia produced by 1 mg/kg naloxone was completely abolished in mice pretreated with nor binaltorphimine, a highly selective kappa-opioid antagonist. Norbinaltorphimine on its own, however, had no effect. These results suggest that the analgesic actions of naloxone may be due to an interaction with kappa receptors. PMID- 1499695 TI - Investigation of how different filters affect some biochemical properties of stored platelet concentrates. AB - The aim of the present study was to investigate how four different filters, i.e. Imugard IG500 (Terumo, Japan), Miropore (Miramed, Italy), Pall P1-100 (Pall, USA) and Sepacell P1-10A (Asahi, Japan) affect some biochemical properties of platelet concentrates. The work was conducted using 42 pairs of platelet concentrates. After 2 days of storage, one of the preparations was filtered and the other served as an unfiltered control. Immediately after filtration, determination of the platelet count, desarginated activated complement factor 3 (C3a des arg) and the extracellular and total concentrations of platelet factor 4 (PF4) and lactate dehydrogenase (LDH) were carried out on both these platelet concentrates. After an additional storage period of 3 d, extracellular concentrations of PF4 and LDH were determined on both concentrates. A significant decrease of extracellular PF4 concentration was found immediately after filtration when Pall P1-100 and Imugard IG500 were used. During the 3-d storage after filtration, the concentrates filtered with Imugard IG500 and Pall P1-100 demonstrated significantly higher platelet lysis as compared to the unfiltered controls. It is concluded that the present work demonstrates storage instability after filtration with Imugard IG500 and Pall P1-100. Therefore, platelet concentrates filtered with these filters would not appear to be suitable for storage. PMID- 1499696 TI - Normal mouse serum-derived factor(s) which inhibits growth of the interleukin-2 dependent cell line CTLL. AB - Evidence is presented for the existence of a serum factor(s) (SF), which inhibits the growth of both the interleukin-2 (IL-2)-dependent cell line CTLL and the 2 day generation of CTL cells. This activity is found in the serum of both nude and euthymic mice and its suppressive effect can be detected about 18 hours after addition to CTLL cultures. The inhibitory activity elutes from a Sepharose 6B gel after the gamma globulin fraction (100-150 kD), and is precipitated by ammonium sulfate at 60 w/v% saturation. IL-3-mediated bone marrow colony formation is not inhibited by SF. It also does not suppress the growth of a panel of different tumor cell lines. The spleen cell responsiveness to both Con A and LPS activation is greatly reduced in the presence of SF. However, binding of radiolabelled IL-2 to CTLL cells was not blocked by SF, although the activity was greatly reduced by absorption to these cells. Our data support the existence of factor(s) in sera that may have a regulatory role on IL-2-mediated functions. PMID- 1499697 TI - Splenic irradiation as initial therapy for prolymphocytic leukemia. PMID- 1499698 TI - DDAVP-induced enhancement of platelet retention: its dependence on platelet-von Willebrand factor and the platelet receptor GP IIb/IIIa. AB - Although DDAVP has been shown to be haemostatically efficacious in patients with various congenital or acquired platelet disorders, no reasonable explanation has been found for this effect. We have previously shown DDAVP to increase platelet adhesiveness as measured with a platelet retention test. The aim of the present study was to investigate the mechanism of action responsible for the increased platelet retention in response to DDAVP. Patients with vWD type III and type Ia, severe haemophilia and severe thrombasthenia, as well as healthy controls, were included in the study. The effect of different concentrations of vWF in plasma and platelets was explored, as was the effect on platelet function of apyrase and monoclonal antibodies against GP IIb/IIIa and GP Ib. We found the effect of DDAVP on platelet retention to be unaffected by changes in the plasma concentration of vWF. The enhanced platelet retention after DDAVP is apparently dependent on the presence of platelet-vWF and on a normal function of the GP IIb/IIIa. The effect is not mediated via ADP or thrombin. The platelet-stimulating effect of DDAVP may be one explanation for the positive haemostatic effect in patients with certain platelet disorders. PMID- 1499699 TI - Effect of smoking on bronchoalveolar lavage constituents. PMID- 1499700 TI - Smoking-induced changes in epithelial lining fluid volume, cell density and protein. AB - Bronchoalveolar lavage has proved a useful research technique for recovering cellular and molecular contents of the lower respiratory tract. Because the recovered fluid is variably diluted, an accurate estimation of molecular and cellular concentrations can only be made if the epithelial lining fluid volume recovered is also known. It has been suggested that smoking may alter epithelial lining fluid volume by reducing clearance or by stimulating production and, thus, affect the interpretation of bronchoalveolar lavage studies. In this study, urea was used as an endogenous marker of epithelial lining fluid volume in a comparison of 26 smokers and 31 nonsmokers. The mean epithelial lining fluid volume recovered from smokers was significantly greater than that of nonsmokers (2.4 +/- 1.40 ml vs 1.2 +/- 0.75 ml, p less than 0.005). The total cellular concentration in the bronchoalveolar lavage fluid in smokers was also greater (94.2 +/- 46 x 10(6) vs 33.9 +/- 21.5 x 10(6) cells per 300 ml lavage), even when corrected for bronchoalveolar lavage volume recovered (63.1 +/- 32.5 x 10(6) vs 24.9 +/- 13.3 x 10(6) cells per 100 ml recovered lavage fluid). This was true for macrophage, lymphocyte and neutrophil cell numbers. However, when corrected for the apparent epithelial lining fluid volume, only the macrophage count remained significantly higher in the smokers compared with nonsmokers (30.66 +/- 20.7 x 10(6) vs 18.21 +/- 8.6 x 10(6) macrophages.ml-1 ELF). In addition, concentrations of albumin and immunoglobulin M (IgM) were significantly lower in smokers after correction for epithelial lining fluid volume. These results highlight smoking as a confounding factor in the interpretation of bronchoalveolar lavage data.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1499701 TI - Radiation-induced increase in hyaluronan and fibronectin in bronchoalveolar lavage fluid from breast cancer patients is suppressed by smoking. AB - Bronchoalveolar lavage (BAL) fluid was analysed from 21 patients with breast cancer, stage T1N0M0, who had undergone tumour resection and post-operative local irradiation (accumulated dose 56 Gy). The lavage was performed two months after radiotherapy, in the anterior part of the lingula (left side) or of the right middle lobe (right side), depending on which side had been exposed to radiation. The patients had significantly increased concentrations of fibronectin (FN) (p less than 0.001), hyaluronan (HA) (p less than 0.01) and albumin (p less than 0.05) in BAL fluid compared with the healthy controls (n = 19). However, when the patients were separated, according to smoking history, it was obvious that the inflammatory reaction occurred entirely in the nonsmoking patient group (n = 10), whilst no difference could be found between the smoking patients (n = 11) and the controls. In the nonsmoking patient group, there was a sevenfold increase in BAL concentrations of FN and a threefold increase in HA. Moreover, four patients had detectable levels of procollagen III peptide in BAL, all were nonsmokers. The smoking habits of the controls had no influence on the BAL measurements. These findings indicate that smoking interferes with the radiation-induced early inflammatory connective tissue reaction of the lung. Finally, the results justify further investigation of interaction of smoking with cancer treatment, both from the view of therapy effectiveness and reduction of adverse effects. PMID- 1499702 TI - Bronchiolitis obliterans organizing pneumonia (BOOP): the cytological and immunocytological profile of bronchoalveolar lavage. AB - The cytological and immunocytological profile of bronchoalveolar lavage (BAL) was studied in 10 patients with idiopathic bronchiolitis obliterans organizing pneumonia (BOOP) and compared with the data in idiopathic pulmonary fibrosis (IPF) (n = 22), chronic eosinophilic pneumonia (CEP) (n = 9), and extrinsic allergic alveolitis (EAA) (n = 24). Lymphocyte subsets were enumerated using an immunoperoxidase slide assay. The BAL pattern in BOOP patients was characterized by several features: 1) colorful cell differentials with an increase in all cell types, most markedly in lymphocytes, and more moderately in neutrophils, eosinophils and mast cells, as well as the presence of foamy macrophages and, occasionally, of plasma cells; 2) decreased CD4/CD8 ratio; 3) normal percentage of CD57+ cells; and 4) increase in activated T-cells in terms of human leucocyte antigen-DR (HLA-DR) expression, and occasionally also interleukin-2 receptor (CD25) expression. The findings were most similar to those in EAA except for the CD25 expression, which was always normal, and the CD57+ cells, which were increased in EAA. The increase in lymphocytes discriminated best between BOOP and IPF. The eosinophils were significantly higher in CEP than in BOOP with little overlap. In conclusion, BAL may be of value to distinguish between BOOP and other interstitial lung disease. PMID- 1499703 TI - Semi-quantitative X-ray microanalysis of bronchoalveolar lavage samples from silica-exposed and nonexposed subjects. AB - To evaluate the possibility of quantifying alveolar dust burden in conditions of exposure to silica, four groups of subjects were submitted to bronchoalveolar lavage (BAL): 10 healthy control subjects and 39 patients affected by diffuse interstitial lung disease (DILD) never exposed to dust, 23 silicotic patients and 12 chronic bronchitis patients with a history of occupational exposure to silica dust. Five to ten million BAL recovered cells were analysed with an energy dispersive X-ray microanalysis (EDXA) system to determine the silicon content, expressed in a semi-quantitative way as silicon to sulphur (Si/S) ratio. The results were independent of smoking habit. The Si/S median values (interquartile range in brackets) for the four groups were 0.53 (0.5-0.65), 0.60 (0.41-0.8), 1.23 (1.06-1.39), 1.31 (1.11-1.97), respectively. Silicotics and simply exposed individuals did not show a significant discrepancy, but they were both significantly different in comparison with normal and DILD patients without history of exposure (p less than 0.001). 14.3% false negative cases were found, and 4.1% false positive cases (none among normal subjects). We did not see any significant relationships between the amount of silicon and the duration of exposure or the degree of chest X-ray involvement. A study of cytocentrifuge slides from the same subjects by polarizing light microscopy revealed a lower sensitivity (34% false negative cases).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1499704 TI - Parenteral administration of trypsin triggers lung emphysema. AB - Eight weeks after a single intravenous injection of trypsin, more than half of 26 treated rats showed pulmonary emphysema, as demonstrated by a significant increase of the mean linear intercept (MLI = 107 microns) in comparison with 11 controls (69 +/- 15 microns) (mean +/- SD). As observed 56 days after the injection, the intraperitoneal administration of trypsin (24 rats) also leads to lung emphysema (MLI = 101-106 microns), as does endotracheal instillation of elastase (13 rats), (MLI = 108 microns). The intraperitoneal administration of trypsin in animals constitutes a model close to human pathology with which lung alterations in acute pancreatitis may be studied. Having no elastolytic properties, trypsin cannot directly induce emphysema. The observation of a pulmonary leucostasis in eight rats sacrificed early after the trypsin injection suggested that leucocyte trapping and activation are important for the genesis of this trypsin-triggered emphysema. PMID- 1499705 TI - Ultrastructural and immunohistochemical studies on the ontogenic development of bronchus-associated lymphoid tissue (BALT) in the rat: special reference to follicular dendritic cells. AB - The ontogenic development of lymphoid and non-lymphoid cells in bronchus associated lymphoid tissue (BALT) of the rat was studied ultrastructurally and immunohistochemically. In the late foetal period, only the alveolar macrophages showed a weak positivity for leucocyte common antigen, but no immune region associated (Ia) antigen was detected by monoclonal antibody, MAS 043. Mast cells were present. At 6 days of age, Ia-positive cells were observed in the alveolar wall and peribronchial interstitial tissue, and ultrastructurally there was an aggregation of the fibroblastoid mesenchymal cells. By 10 days of age, the aggregation of lymphoid cells together with S-100-positive reticulum cells had formed a BALT-like periarterial lymphoid sheath. In the adult animals, an obvious B-cell area was present in the central part and subepithelium of BALT, whilst in this area, S-100-positive, strongly Ia-positive cells with a dendritic form were observed. These dendritic cells appeared to be identical to the follicular dendritic cells (FDC) seen in the secondary follicles of lymphoid organs. Those cells may be derived from the fibroblastic reticulum cells, and may function to present antigen to lymphocytes. PMID- 1499706 TI - Bronchial responsiveness and work-related asthma in aluminium potroom workers: effect of removal from exposure. AB - Twelve subjects relocated from aluminium potrooms due to work-related asthma were followed up for 2-27 months (median 23 months). Repeated post-relocation examinations (numbering 3-7, median 6) of methacholine challenge, forced expiratory volume in one second (FEV1), eosinophil cell count and respiratory symptoms were carried out at regular intervals. At the time of relocation, bronchial hyperresponsiveness (provoking concentration producing a 20% fall in FEV1 (PC20) less than or equal to 8.0 mg.ml-1) was found in eight of the subjects. During the follow-up period a twofold increase in PC20 was found in 7 of the 8 subjects who had PC20 less than 8.0 mg.ml-1 at the time of relocation. There was an improvement of symptoms but no improvement in FEV1 or decrease of eosinophils during the follow-up examinations. PMID- 1499707 TI - Diurnal variation in FEV1 after heart-lung transplantation. AB - We have examined the diurnal variation in forced expiratory volume in one second (FEV1) in 25 heart-lung transplantation patients over a four week period in order to study the pathophysiological mechanisms underlying the increased mortality and morbidity which occurs at night in asthma. These patients do not have pulmonary autonomic nervous reflexes, but often have muscarinic receptor hypersensitivity. They also develop mixed cell infiltration of the lung tissue in the course of infection or rejection. Thus, they show many features in common with asthma. Seventeen patients (68%) showed a significant diurnal variation in airway calibre (mean amplitude of FEV1 was 4.6% (SD 3.7%)), which is similar to that reported in normal adults. One patient had a diurnal variation of 34.5% during an episode of rejection. This variation fell to 6.9% after steroid therapy, a change often seen in asthma. There was a correlation between increased amplitude of the variation and the presence in transbronchial biopsies of airway submucosal eosinophils and lymphocytes, associated with a histological diagnosis of acute rejection and with epithelial damage. No association was seen with muscarinic receptor sensitivity. The variation in FEV1 showed no alteration from the normal day/night synchronization, and the peak values were around 1300 h. We conclude that the diurnal variation in FEV1 after heart-lung transplantation is not dependent on autonomic nerve reflexes or muscarinic receptor sensitivity, but is related to the consequences of inflammation described above. PMID- 1499708 TI - Adaptation of cough reflex with different types of stimulation. AB - Inhalation cough challenge has become an accepted method of investigating antitussive agents. It is, therefore, important to examine the degree of tachyphylaxis seen with repeated cough challenge. In addition, different types of challenge may reveal important differences in the neuronal pathways involved in the cough reflex. Citric acid, distilled water and capsaicin were examined to determine adaptation of the cough response during acute and long-term inhalation studies in healthy subjects. To study acute tachyphylaxis two separate one minute continuous inhalation challenges (n = 13) were performed. Long-term tachyphylaxis (n = 10) was examined using citric acid and capsaicin inhalation at 10 min intervals for 40 min, and at 4 and 6 h. Cross-tachyphylaxis to citric acid and capsaicin was examined in a separate randomized crossover study (n = 10). Highly significant adaptation occurred between the first and last 10 s of the one minute challenge with citric acid (90-100%) and distilled water (74-84%), but was less pronounced with capsaicin (37-49%, at 2 microM). Cough during the whole of the second test was significantly reduced for citric acid (50%). During long-term challenge cough was attenuated over 40 min both with citric acid (100 mM, p less than 0.05; 300 mM, p less than 0.001; 1 M, p less than 0.001) and with capsaicin (3 microM, p less than 0.01; 10, 30, 100 microM, p less than 0.001 each). With higher doses, tachyphylaxis was still present at 180 min with both citric acid (300 mM, p less than 0.05) and capsaicin (100 microM, p less than 0.008).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1499709 TI - Adherence to entry criteria and one year experience of long-term oxygen therapy in Poland. AB - The adherence to entry criteria and results of one year long-term oxygen therapy (LTOT) in Poland were analysed. Four hundred and seven patients with advanced respiratory failure due to chronic lung diseases qualified for LTOT were observed for one year in 12 regional LTOT centres. There were 315 patients with chronic obstructive pulmonary disease (COPD) and 92 with other chronic lung diseases. In 270 patients the prescription of oxygen was based on the single criterion of stable arterial oxygen tension (PaO2) less than or equal to 55 mmHg (7.3 kPa); and in the remaining 137 with less severe stable hypoxaemia (PaO2 56-65 mmHg) (7.4-8.6 kPa), on concomitant signs of cor pulmonale and/or of tissue hypoxia. Of 407 patients who started LTOT, 95 (23%) died during the first year of treatment. The mortality rate was 21% for COPD patients and 33% for patients with other lung diseases. After one year of LTOT 312 patients survived: 250 COPD patients and 62 with other lung diseases. Of these, 19 COPD patients (8%) and 9 with other chronic lung disease (15%) who had PaO2 less than or equal to 55 mmHg (7.3 kPa) when oxygen was prescribed, presented with PaO2 greater than 55 mmHg (7.3 kPa). From the 137 patients (106 with COPD and 31 with other lung diseases) who qualified with less severe hypoxaemia, 10 COPD patients (10%) and 5 (16%) with other lung disease had PaO2 greater than 65 mmHg (8.6 kPa).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1499710 TI - Changes in heart rate during obstructive sleep apnoea. AB - The mechanisms behind the decrease in heart rate during apnoeas in patients with obstructive sleep apnoea (OSA) are little known. Recent findings in animal experiments indicate that stimulation of the upper airway activates postinspiratory and cardiac vagal neurones in the medullary respiratory centre, causing alterations in heart rate and respiratory rhythm. Since OSA leads to a collapse of the airway and consequent stimulation of upper airway receptors, we studied the interrelations between heart rate and respiratory rhythm during apnoea and during negative intrathoracic pressure generated by the Mueller manoeuvre (MM). Fifteen patients with OSA (apnoea hypopnoea index (AHI) 45 +/- 28.h-1) were studied by polysomnography, during a MM and a Valsalva manoeuvre, each of 15 s duration. The heart rate decrease (delta HRA) and the increase in total respiratory cycle duration (TOT) were evaluated during apnoea in non-rapid eye movement (REM) sleep. Patients with OSA demonstrated a decrease in heart rate during apnoea (-14.4 +/- 9.0 beats.min-1), and during MM (-11.5 +/- 13.5 in OSA vs 3.1 +/- 7.8 beats.min-1 in a control group). TOT increased during apnoea (4.6 +/- 3.1 s). There was a significant correlation between delta HRA and AHI (r = 0.64) as well as between delta HRA and increase in TOT (r = 0.62). These findings indicate that upper airway obstruction may cause an activation of receptors at the site of airway collapse or distortion leading to changes in heart rate and respiratory rhythm. PMID- 1499711 TI - Haemodynamic effects of short-term nasal continuous positive airway pressure therapy in sleep apnoea syndrome: monitoring by a finger arterial pressure device. AB - We have evaluated the effects of short-term nasal continuous positive airway pressure (nCPAP) therapy on systemic blood pressure and heart rate in patients with obstructive sleep apnoea syndrome. Twenty five consecutive patients were examined during baseline conditions (No-CPAP) and during one night of nCPAP treatment (CPAP). The mean value and the variation coefficient of cardiovascular variables, examined by a finger arterial pressure device (Finapres), were determined in wakefulness and sleep. Without nCPAP an increase in blood pressure from wakefulness to sleep was observed in all patients from 138 +/- 3 mmHg to 146 +/- 3 and 155 +/- 4 mmHg, and from 80 +/- 1 mmHg to 82 +/- 2 and 84 +/- 2 mmHg, respectively, for systolic and diastolic values in non rapid eye movement (NREM) and rapid eye movement (REM) sleep. Conversely, heart rate decreased from 75 +/- 2 beats.min-1 to 70 +/- 2 and 69 +/- 2 beats.min-1. In addition, variability of heart rate and blood pressure was greatly increased compared with the awake state. Short-term nCPAP therapy significantly reduced systolic pressure from 144 +/- 3 mmHg to 137 +/- 3 and 143 +/- 4 mmHg during NREM and REM sleep, respectively, associated with a decrease in heart rate (from 69 +/- 2 to 65 +/- 2 beat.min-1). In total sleep and in all sleep stages a significantly reduced variability (p less than 0.001) was found. No changes were observed for diastolic pressure during CPAP night compared with baseline conditions.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1499712 TI - Respiratory function during wakefulness and sleep among survivors of respiratory and non-respiratory poliomyelitis. AB - The purpose of this study was to determine whether there is a difference in respiratory mechanics and gas exchange between polio survivors and healthy, age matched controls during wakefulness and sleep. Polio survivors were divided into four groups. The first group included those who had evidence of respiratory muscle involvement originally (PRM) and the second group included those who had bulbar muscle involvement originally (PBM). The third and fourth groups had only limb involvement originally but were separated by absence (PSL) or presence of a scoliosis (PSS) at the time of their evaluation. Each subject completed baseline and one year follow-up measurements of lung volumes, diffusion, flow rates, respiratory muscle strength, central and peripheral chemoreflexes and arterial blood gases. Sleep measurements included a full respiratory polysomnographic study. Fifty polio survivors and 13 controls completed the study. The PRM and PSS groups had an elevated arterial carbon dioxide tension (PaCO2) (mean +/- SE 6.0 +/- 0.4 and 6.0 +/- 0.3 kPa, respectively), reduced vital capacity (2.8 +/- 0.3 and 2.9 +/- 0.3 l, respectively), reduced maximal inspiratory pressure (-5.9 +/- 0.7 and -5.4 +/- 0.8 kPa, respectively) and reduced maximal expiratory pressure (9.8 +/- 1.1 and 9.1 +/- 1.2 kPa, respectively), when compared with non-polio controls. During sleep PRM and PSS groups experienced a higher PaCO2 (6.5 +/- 0.5 and 6.7 +/- 0.4 kPa, respectively) and a lower arterial oxygen saturation (SaO2) (89 +/- 4 and 86 +/- 3%, respectively). There were no differences among groups for diffusion, flow rates and chemoreflexes. All other polio survivors showed essentially normal respiratory function.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1499713 TI - Respiratory mechanics studied by multiple linear regression in unsedated ventilated patients. AB - Respiratory mechanics during artificial ventilation are commonly studied with methods which require a specific respiratory pattern. An alternative is to analyse the relationship between tracheal pressure (P) and flow (V') by multiple linear regression (MLR) using a suitable model. The value of this approach was evaluated in 12 unsedated patients, mechanically-ventilated for acute respiratory failure, and most with a history of chronic obstructive or restrictive respiratory disease. After correction for the non-linear resistance of the endotracheal tube, the data were analysed with the linear first order model: P = P0 + E.V + R.V' where E and R are total respiratory elastance and resistance, and P0 is the static recoil pressure at end-expiration. After exclusion of the cycles which clearly exhibited muscular activity, a good fit was observed in 25 out of 36 records (relative root-mean-square error less than 10%); the values of E and R were reproducible within cycles, and consistent with the patient's condition and the ventilatory mode. The intrinsic positive end-expiratory pressure (PEEPi), as derived from P0 and the applied PEEP, averaged 1.1 +/- 1.0 hPa. Using more sophisticated models, allowing for mechanical non-homogeneity or non-linearity of R or E, rarely improved the fit and often provided unrealistic data. In several subjects the discrepancy between the data and the first order model was consistent with expiratory flow limitation, which may severely impair the analysis. We conclude that, except in the case of expiratory flow limitation, the method is useful for routine clinical use and better implemented with the simple linear model. PMID- 1499714 TI - Lung volumes measured by the forced rebreathing technique in children with airways obstruction. AB - Forced rebreathings may recruit trapped gas into the mixing process. Therefore, we assessed the validity and reproducibility of measurements of residual volume (RVN2) by forced rebreathing in a closed circuit using N2 as indicator gas (N2FR) in children with airways obstruction. Validity was studied from measurements of RV obtained by N2FR, by helium dilution during resting ventilation, and by body plethysmograph at low panting frequency in young patients (8-18 yrs, 13 with asthma, forced expiratory volume in one second (FEV1) 93.0 +/- 22.8% pred; 12 with cystic fibrosis (CF), FEV1 80.4 +/- 16.4% pred). Reproducibility of RVN2 was assessed from duplicate measurements in 73 patients with asthma before and after bronchodilation (FEV1 81.4 +/- 13.7 and 99.6 +/- 11.5% pred, respectively), and in nine patients with CF; the total lung capacity (TLC) was unaffected by bronchodilation; 3,797 +/- 830 ml and 3,807 +/- 843 ml, respectively. Gas dilution methods gave comparable results in all subjects but gave lower values than plethysmography in patients with cystic fibrosis. Reproducibility was satisfactory, median differences between duplicate measurements of RVN2 and TLCN2 varying between 13 and 46 ml, respectively. We conclude that N2FR is quickly performed and well-tolerated. Lung volumes are highly reproducible and agree well with those obtained with the helium dilution method. Deep inspirations do not seem to overcome gas trapping in patients with CF. PMID- 1499715 TI - Update on an exposure system for particles in the diagnosis of occupational asthma. AB - We have previously designed a system for exposure to particles and described the preliminary results in 20 subjects exposed to occupational sensitizers in powder form (Cloutier Y, et al. - Eur Respir J, 1989; 2: 769). Modifications have been made to the particles generator, exposure chamber and sampling ports. Furthermore, in order to improve the stability of concentrations in the exposure chamber and to make the system easy to operate by a technician, it has been completely automated using closed-loop feedback regulated by a computer program. PMID- 1499716 TI - Intraventricular rifampicin in severe tuberculous meningo-encephalitis. AB - We present a patient acutely ill from severe tuberculous meningo-encephalitis, in whom acute hepatic and renal failure, due to intercurrent septic shock, precluded the administration of full systemic dosage of antituberculous drugs. Daily direct intraventricular administration of 5 mg rifampicin, via a subcutaneous Ommaya reservoir connected to a catheter placed in the right lateral cerebral ventricle, resulted in rapid improvement without neurological sequelae. Intraventricular rifampicin administration for 50 consecutive days was well-tolerated without local or systemic side-effects. In well-selected patients with severe tuberculous meningo-encephalitis, intraventricular rifampicin may safely and highly effectively be added to systemic antituberculous therapy. PMID- 1499717 TI - Progesterone action through aggregation of a receptor on the sperm plasma membrane. AB - Rapid steroid effects, reported in several cell types, have pointed out the possibility of non-genomic mechanisms of action, presumably on cell surface receptors. Here we analyzed the effects of antibody-mediated aggregation of a novel type of progesterone receptor on the plasma membrane of human sperm cells. We report that aggregation of hormone-receptor complexes induces Ca2+ influx and a Ca(2+)-dependent exocytotic event in this system. These data suggest a possible mechanism for rapid steroid-induced events. Further research is warranted to examined if a similar mechanism is involved in rapid steroid effects in other cell types. PMID- 1499718 TI - Activation of protein kinase C by the 14-3-3 proteins homologous with Exo1 protein that stimulates calcium-dependent exocytosis. AB - The 14-3-3 proteins are a family of acidic proteins found mainly in the brain and are suggested to have a role in monoamine synthesis based on their ability to activate tyrosine and tryptophan hydroxylases in the presence of type II Ca2+/calmodulin-dependent protein kinase. Recently, however, it has been demonstrated that a member of the 14-3-3 family, termed Exo1, stimulates Ca(2+) dependent exocytosis in permeabilized adrenal chromaffin cells, suggesting that this protein family may influence the protein kinase C-mediated control of Ca(2+) dependent exocytosis. Here we show that the 14-3-3 proteins activate protein kinase C at about 2-fold more than the known level of the activated protein kinase, i.e. the activity of protein kinase C in the presence of Ca2+ and phospholipids. This raises the possibility that the cellular activity of protein kinase C is regulated by diverse members of the 14-3-3 family and that the reported ability of Exo1 to reactivate Ca(2+)-dependent exocytosis is based on its stimulatory effect on protein kinase C activity. The 14-3-3 family, therefore, appears to be a multifunctional regulator of cell signalling processes mediated by two types of Ca(2+)-dependent protein kinase, protein kinase C and type II calmodulin-dependent protein kinase. PMID- 1499719 TI - Over-expression of human phospholipase C-gamma 2 enhances platelet-derived growth factor-induced mobilization of intracellular Ca2+ and the release of arachidonic acid and prostaglandins in NIH 3T3 fibroblasts. AB - Over-expression of human phospholipase C-gamma 2 in murine NIH 3T3 fibroblasts has been shown to result in an increased platelet-derived growth factor-mediated formation of inositol phosphates. Here we show that phospholipase C-gamma 2 over expression is associated with an increased platelet-derived growth factor mediated release of arachidonic acid, prostaglandin E2, 6-keto prostaglandin F1 alpha and prostaglandin F2 alpha. The phorbol ester, calcium ionophore- and fluoride-induced release of arachidonate and its metabolites is not affected by phospholipase C-gamma 2 over-expression. Over-expression of phospholipase C-gamma 2 is also associated with an enhancement of platelet-derived growth factor induced change in intracellular Ca2+. These results demonstrate that stimulation of recombinant human phospholipase C-gamma 2 induces a change in the intracellular Ca2+ concentration, a release of arachidonic acid and formation of prostaglandins in NIH 3T3 cells. In control cells platelet-derived growth factor induced activation of arachidonic acid cascade is rate-limited by the endogenous phospholipase C. PMID- 1499720 TI - Purification and characterization of glycerol-3-phosphate dehydrogenase of Saccharomyces cerevisiae. AB - The NAD-dependent glycerol-3-phosphate dehydrogenase (glycerol-3-phosphate:NAD+ oxidoreductase; EC 1.1.1.8; G3P DHG) was purified 178-fold to homogeneity from Saccharomyces cerevisiae strain H44-3D by affinity- and ion-exchange chromatography. SDS-PAGE indicated that the enzyme had a molecular mass of approximately 42,000 (+/- 1,000) whereas a molecular mass of 68,000 was observed using gel filtration, implying that the enzyme may exist as a dimer. The pH optimum for the reduction of dihydroxyacetone phosphate (DHAP) was 7.6 and the enzyme had a pI of 7.4. NADPH will not substitute for NADH as coenzyme in the reduction of DHAP. The oxidation of glycerol-3-phosphate (G3P) occurs at 3% of the rate of DHAP reduction at pH 7.0. Apparent Km values obtained were 0.023 and 0.54 mM for NADH and DHAP, respectively. NAD, fructose-1,6-bisphosphate (FBP), ATP and ADP inhibited G3P DHG activity. Ki values obtained for NAD with NADH as variable substrate and FBP with DHAP as variable substrate were 0.93 and 4.8 mM, respectively. PMID- 1499721 TI - Investigation of spatial relationships and energy transfer between complexes B800 850 and B890-RC from Chromatium minutissimum reconstituted into liposomes. AB - Spatial relationships between different pigment-protein complexes in the membranes of the purple photosynthetic bacterium, Chromatium minutissimum, have been studied. The possibility of restoring the function of efficient excitation energy transfer from bacteriochlorophyll molecules to the reaction centers in the system of soybean liposomes, reconstituted with pigment-protein complexes B800 850 and B890-RC from C. minutissimum, has been explored. The chemical cross linking method, together with stationary and picosecond spectrally resolved fluorescence measurements were employed. It has been shown that after the incorporation of the complexes into the liposome membranes conditions for directed excitation energy transfer from the light-harvesting pigments to the reaction centers are created, which are less optimal, however, than those in the native state. Possible reasons are considered. PMID- 1499722 TI - Effect of RU 38486 on TNF production and toxicity. AB - Glucocorticoid steroids provide considerable protection against the systemic toxicity of tumor necrosis factor-alpha (TNF-alpha, cachexin). In animal experiments RU 38486 (mifepristone), a steroid antagonist, increased the synthesis of TNF and sensitized the animals to the cytotoxic action of TNF. As compared to the control and methylprednisolone-treated groups, mifepristone significantly increased the level of TNF in the serum, liver and spleen of lipopolysaccharide (LPS)-treated animals. In tissue cultures RU 38486 induced the TNF synthesis of myeloid cells and increased the TNF production of genetically modified HeLa cells, which synthesize TNF constitutively. Normal and tumor cell cultures exhibited increased sensitivity toward TNF in the presence of mifepristone. PMID- 1499723 TI - Mapping and sequence-specific identification of phosphopeptides in unfractionated protein digest mixtures by matrix-assisted laser desorption/ionization time-of flight mass spectrometry. AB - We have demonstrated a procedure for the rapid (minutes), sensitive (less than pmol), and sequence-specific identification of phosphopeptides in unfractionated digests of phosphoproteins using matrix-assisted UV laser desorption/ionization (MALDI) time-of-flight (TOF) mass spectrometry. The mass-dependent identification of one specific 13-residue phosphopeptide (S105-K117), observed among the 153 possible trypsin digest fragments of human beta-casein (211 residues), was confirmed by amino acid sequence analysis of the 33P-labeled peptide after isolation by reverse-phase HPLC. MALDI-TOF was also used to monitor the rate and extent to which an 18-residue N-terminal beta-casein peptide (R1-K18) was phosphorylated in vitro. These results demonstrate that MALDI-TOF may be used (i) to facilitate the identification of sequence-specific sites of protein phosphorylation and dephosphorylation, (ii) to monitor protein and peptide phosphorylation and dephosphorylation reaction rates, even in complex unfractionated mixtures, (iii) to determine the minimum primary structure necessary for the phosphorylation of specific protein surface domains, and (iv) to evaluate the effects of intact protein phosphorylation and dephosphorylation on susceptibility to subsequent proteolytic events. PMID- 1499724 TI - Glycoprotein-binding site of dystrophin is confined to the cysteine-rich domain and the first half of the carboxy-terminal domain. AB - Dystrophin, a protein product of the Duchenne muscular dystrophy gene, is thought to associate with the muscle membrane by way of a glycoprotein complex which was co-purified with dystrophin. Here, we firstly demonstrate direct biochemical evidence for association of the carboxy-terminal region of dystrophin with the glycoprotein complex. The binding site is found to lie further inward than previously expected and confined to the cysteine-rich domain and the first half of the carboxy-terminal domain. Since this portion corresponds well to the region that, when missing, results in severe phenotypes, our finding may provide a molecular basis of the disease. PMID- 1499725 TI - Characterisation of a human bilirubin UDP-glucuronosyltransferase stably expressed in hamster lung fibroblast cell cultures. AB - A cDNA encoding a human bilirubin UDP-glucuronosyltransferase has been isolated and stably expressed in Chinese hamster V79 lung fibroblast cell line. Western blotting of cell homogenates with anti-UGT antibody revealed a highly expressed protein of approx. 55.5 kDa in size. The expressed enzyme specifically catalysed the formation of bilirubin mono- and diglucuronides, and also catalysed the glucuronidation of two phenolic compounds, which are good substrates for other human UGT isoenzymes, at low rates. PMID- 1499726 TI - Protein synthesis in HL-60 cells treated with DMSO and hypoxanthine. AB - Short-term treatment of the HL-60 cells with DMSO and hypoxanthine, inducers of granulocytic differentiation, was reported to cause a rapid increase in protein synthesis. This effect was ascribed to the insertion of inosine in the wobble position of the tRNA anticodon and consequently increasing codon recognition potential. In this study we have re-investigated the effects of DMSO and/or hypoxanthine on protein synthesis. In contrast to their findings we were unable to demonstrate stimulated protein synthesis in either short- or long-term treatment with these agents. Polysome analysis under these conditions revealed that polysomes were disaggregated. Finally, the activity of tRNA-hypoxanthine ribosyltransferase, an enzyme responsible for the insertion of inosine in the anticodon, was also relatively low. Under these circumstances, we propose that tRNA modification is not essential in the regulation of protein synthesis. PMID- 1499727 TI - Human immunodeficiency virus type 1 productive infection in staurosporine-blocked quiescent cells. AB - Staurosporine, an antibiotic known to inhibit cellular protein kinases, can reversibly block the progress of normal and tumour cells into the cell cycle. The ability of HIV-1 to infect and replicate in cells blocked by staurosporine was investigated. The results show that blocked, non-cycling cells can be productively infected by HIV-1, steadily releasing infectious progeny virus for several weeks. This suggests that at least in some cases, HIV-1 can be found in a stable and active state in resting, non-proliferating T cells. PMID- 1499728 TI - Production and secretion of plasminogen in cultured rat brain microglia. AB - The production and secretion of plasminogen in cultured rat brain microglia was investigated. Urokinase-dependent caseinolytic activity was detected by zymography in microglial conditioned medium with a molecular weight of about 90 kDa. The 90-kDa protein was also detected by Western blotting with anti-rat plasminogen antiserum in the non-reducing condition. Immunoprecipitation with plasminogen antiserum following [35S]methionine labelling revealed that the plasminogen detected in microglial conditioned medium is synthesized in microglia. The amount of plasminogen in the conditioned medium was increased by stimulation with lipopolysaccharide. These results show that cultured microglia produce plasminogen and secrete it into the culture medium. PMID- 1499729 TI - MAP kinase kinase from rabbit skeletal muscle. A novel dual specificity enzyme showing homology to yeast protein kinases involved in pheromone-dependent signal transduction. AB - MAP kinase kinase (MAPKK) was purified 30,000-fold to homogeneity from extracts of rabbit skeletal muscle and shown to be a monomeric protein of apparent molecular mass 44 kDa. MAPKK activated the 42 kDa isoform of MAP kinase by phosphorylation of Thr-183 and Tyr-185, and phosphorylated itself slowly on tyrosine, threonine and serine residues, establishing that it is a 'dual specificity' protein kinase. Peptide sequences from MAPKK were homologous to other protein serine/threonine kinases, especially to the subfamily that includes yeast protein kinases that lie upstream of yeast MAP kinase homologues in the pheromone-dependent mating pathways. PMID- 1499730 TI - Reversal of oxidative phosphorylation in submitochondrial particles using glucose 6-phosphate and hexokinase as an ATP regenerating system. AB - During steady-state, the Pi released in the medium is derived from glucose-6 phosphate which continuously regenerates the ATP hydrolyzed. A membrane potential (delta psi) can be built up in submitochondrial particles using glucose-6 phosphate and hexokinase as an ATP-regenerating system. The energy derived from the membrane potential thus formed, can be used to promote the energy-dependent transhydrogenation from NADH to NADP+ and the uphill electron transfer from succinate to NAD+. In spite of the large differences in the energies of hydrolysis of ATP (delta G degrees = -7.0 to -9.0 kcal/mol) and of glucose-6 phosphate (delta G degrees = -2.5 kcal/mol), the same ratio between Pi production and either NADPH or NADH formation were measured regardless of whether millimolar concentrations of ATP or a mixture of ADP, glucose-6-phosphate and hexokinase were used. Rat liver mitochondria were able to accumulate Ca2+ when incubated in a medium containing hexokinase, ADP and glucose-6-phosphate. The different reaction measured with the use of glucose-6-phosphate and hexokinase were inhibited by glucose concentrations varying from 0.2 to 2 mM. Glucose shifts the equilibrium of the reaction towards glucose-6-phosphate formation thus leading to a decrease of the ATP concentration in the medium. PMID- 1499731 TI - Nerve growth factor rapidly regulates VGF gene transcription through cycloheximide sensitive and insensitive pathways. AB - Nerve growth factor (NGF) initiates and maintains a regulatory cascade, involving gene induction, which results in the neuronal differentiation of PC12 cells. The VGF gene encodes one of the most rapidly induced neuronal mRNAs identified in NGF treated PC12 cells [Science, 229 (1985) 393-395; Mol. Cell Biol., 11 (1991) 2335 2349]. In this communication we show that NGF-treatment for 60-90 min maximally increases VGF gene transcription by 12- to 14-fold. VGF mRNA half-life was found to substantially decrease in PC12 cells treated with NGF for 9-25 h. Partial inhibition of VGF gene transcription and superinduction of cytoplasmic VGF mRNA levels in the presence of both NGF and cycloheximide suggests that the VGF gene may be regulated through multiple pathways, some of which can be activated in the presence of protein synthesis inhibitors as are the immediate early genes, while others require newly synthesized proteins. PMID- 1499732 TI - Rat liver BiP/GRP78 is down-regulated by a peroxisome-proliferator, clofibrate. AB - Administration of clofibrate in rat results in down-regulation of several liver proteins and a vast induction of peroxisomal proteins. One protein was identified as BiP/GRP78 using antibodies and cDNA cloning. The level of mRNA was reduced by the drug. PMID- 1499733 TI - Is the cytosolic catalase induced by peroxisome proliferators in mouse liver on its way to the peroxisomes? AB - Dietary treatment of male C57B1/6 mice with clofibrate, nafenopin or WY-14.643 resulted in a modest (at most 2-fold) increase in the total catalase activity in the whole homogenate and mitochondrial fraction prepared from the livers of these animals. On the other hand, the catalase activity recovered in the cytosolic fraction was increased 12- to 18-fold, i.e. 30-35% of the total catalase activity in the hepatic homogenate was present in the high-speed supernatant fraction after treatment with these peroxisome proliferators. A study of the time course of the changes in peroxisomal and cytosolic catalase activities demonstrated that the peroxisomal activity both increased upon initiation of exposure and decreased after termination of treatment several days after the increase and decrease, respectively, in the corresponding cytosolic activity. This finding suggests that the cytosolic catalase may be on its way to incorporation into peroxisomes. PMID- 1499734 TI - Phosphorescence and ODMR study of the binding interactions of acetylcholine receptor alpha-subunit peptides with alpha-cobratoxin. AB - Optical detection of magnetic resonance (ODMR) and phosphorescence spectroscopy have been applied to synthetic peptides derived from the alpha-subunit of the nicotinic acetylcholine receptor of Torpedo californica and their complexes with alpha-cobratoxin (CBTX). The CBTX Trp phosphorescence is strongly quenched by the proximal disulfide linkage, while the emission wavelengths and ODMR frequencies of the 18-mer alpha 181-198 indicate a more hydrophobic Trp environment than in the 12-mer alpha 185-196. Binding to CBTX produces a subtle increase in the hydrophobicity of the Trp environment for the peptides, in qualitative agreement with a recently proposed binding model, in which a receptor Trp residue interacts strongly with a hydrophobic cleft of the toxin. PMID- 1499735 TI - Intimal hyperplasia. PMID- 1499736 TI - Endothelial cell injury secondary to surgical preparation of reversed and in situ saphenous vein bypass grafts. AB - Failure of infra-inguinal vein grafts appears to be due to the development of intrinsic lesions (intimal hyperplasia, fibrous stenoses) within the graft which lead to narrowing of the lumen, poor blood flow and thrombosis. The cause of these lesions remains unknown but recently it has been suggested that endothelial injury might be an aetiological factor. The damage that can occur after preparation of reversed vein grafts includes loss of endothelial cells and functional impairment of those cells that remain, in that the ability to produce prostacyclin and endothelium-derived relaxing factor (EDRF) is reduced. The preparation of in situ grafts is different to that for reversed grafts in that a valvulotome is passed along the lumen of the vein to destroy the valves. However, little is known about the degree of endothelial injury that this technique causes. Vein samples were obtained from patients undergoing infra-inguinal and coronary artery bypass grafting. The veins were mounted in an organ bath system to measure isometric tension and exposed to the endothelium-dependent agents acetylcholine, bradykinin, adenosine, histamine and the endothelium-independent agent sodium nitroprusside. The results indicate that preparation of reversed vein grafts leads to some loss of endothelial cells with functional impairment of the cells that remain. However, preparation of in situ grafts leads to severe or total loss of endothelial cells which resulted in an absence of detectable EDRF release. These findings were confirmed by histological examination of the vein samples. PMID- 1499737 TI - The effect of infrarenal aortic reconstruction on glomerular filtration rate and effective renal plasma flow. AB - Compromised patients with aortic disease are vulnerable to various complications from aortic reconstruction. These complications are related to changes in systemic haemodynamics during aortic cross-clamping, which leads to cardiac stress and alteration in regional blood flow to different organs. One of the most important postoperative complications is renal failure which is associated with a high mortality rate. Circulatory alterations within the kidney must play a role in the pathogenesis of renal dysfunction that may follow infrarenal aortic cross clamping and reconstruction. To study the effects of abdominal aortic reconstruction on renal function and perfusion, we measured prospectively the glomerular filtration rate (GFR, n = 59), effective renal plasma flow (ERPF, n = 38) and left ventricular ejection fraction (LVEF, n = 38) in patients undergoing elective infrarenal aortic reconstruction. Radionuclide techniques were used. The three parameters were measured at three time points: preoperatively, postoperatively and 6 months after surgery. The LVEF was measured in order to reflect the patient's cardiac status and pre-renal perfusion. We also measured the three parameters in two control groups of patients: a group of patients undergoing major colonic surgery and a group of patients with arterial disease under conservative management. Six months after surgery the GFR had decreased in 67% of aortic reconstruction patients. Overall GFR in the aortic reconstruction group decreased by a mean of 9 ml min-1 (p = 0.007). This was associated with a decrease in the ERPF in 48.5% of patients. The mean decrease in ERPF in the aortic reconstruction group was 74 ml min-1 (p = 0.05). The LVEF was unchanged.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1499738 TI - The carotid stump syndrome. AB - Transient ischaemic attacks (TIAs) following internal carotid artery occlusion are not uncommon. Micro-embolisation from an ipsilateral internal carotid artery stump has been implicated in the pathogenesis of such TIAs. We report six patients who had persistent TIAs in association with an occluded ipsilateral internal carotid artery and a carotid stump. Four patients who underwent surgery and stump exclusion remain asymptomatic at 2 years while of two patients who were treated with antiplatelet therapy, one remains asymptomatic and one died from a cerebro-vascular accident. PMID- 1499739 TI - Ultrastructural analysis of pseudo-intimal hyperplasia of polytetrafluoroethylene prostheses implanted into the venous and arterial systems. AB - To evaluate and compare the pathogenesis of pseudo-intimal hyperplasia (PH) of venous and arterial prostheses, a segment of the inferior vena cava (n = 16) or abdominal aorta (n = 16) was substituted by a 3 mm internal diameter polytetrafluoroethylene tube graft (PTFE, 3 cm long, 30 microns in nodal distance) in albino rabbits. At designated time intervals (3-28 days) after the replacement, graft patency was examined and the dry weights of the intraluminal deposits measured as an indicator of the degree of PH. The harvested grafts were then subjected to an ultrastructural analysis by means of light microscopy (LM), and scanning electron and transmission electron microscopy (SEM, TEM). All the grafts remained patent during the entire observation period. The PH judged by the dry weight was significantly more extensive in the venous than in the arterial prostheses. The PH on day 28, observed by light microscopes was apparently most extensive in the mid-portion of venous prostheses but in the arteria prostheses it was mostly seen at the anastomotic sites. The lining of the intraluminal surface of the prostheses with endothelial-like cells observed by SEM was faster and more extensive in venous than in arterial prostheses. The process of PH in venous prostheses observed by TEM may be divided into the following steps: early thrombosis, phagocytosis of the thrombus, appearance of fibroblasts, growth of endothelial-like cells, appearance of smooth muscle cells, and pseudointimal thickening and proliferation of fibroblasts producing collagen fibrils. The process in arterial prostheses was essentially identical to that in venous prostheses but was much slower and less extensive. From these observations, it was concluded that the formation of PH occurs much faster in venous than in arterial prostheses, although the mechanism of PH is mostly identical in venous and arterial prostheses. PMID- 1499740 TI - The reproducibility of colour-coded duplex scanning in measuring arterial wall dimensions. AB - Intimal hyperplasia continues to be a major problem following vascular surgery but experimental evidence suggests that it can be reduced pharmacologically. For clinical studies an accurate, reproducible and non-invasive image of the intima and lumen is required. We have assessed the value of the Acuson 128 Colour Duplex for such studies. Ten patients had their common femoral arteries scanned at a fixed point by two experienced observers on two separate occasions. External vessel diameter, luminal diameter and internal diameter (i.e. the diameter within the internal elastic lamina) were measured in both longitudinal and cross sectional views. Cross-sectional area and degree of stenosis were all measured and all parameters expressed as limits of agreement. The mean external diameter of the common femoral arteries was 10.5 +/- 1.6 mm. Measurements in the longitudinal view were highly reproducible with limits of agreement ranging from 0.67 - +0.25 mm (internal diameter) to -1.49 - +1.31 mm (luminal diameter). In order to detect a meaningful change in longitudinal external diameter a real difference of 0.86 mm is required representing a change of less than 10%. Cross sectional diameter measurements were similarly reproducible (-0.73 - +0.47 mm to 1.97 - +1.79 mm). However, cross-sectional area measurements had a wide variation so that the error in degree of stenosis was -25.4 - +30.2%. Thus, duplex ultrasound reproducibly images the layers of the arterial wall. Prospective studies of intimal hyperplasia are feasible but must be based on longitudinal and cross-sectional diameters rather than cross-sectional areas. PMID- 1499741 TI - Endothelial cell seeding after carotid endarterectomy in a canine model reduces platelet uptake. AB - Post-endarterectomy platelet deposition may play an important role not only in vessel wall healing, but also in the development of progressive stenosis. Using a canine model, we investigated the effect of endothelial cell seeding on platelet deposition on endarterectomised arteries. Thirteen dogs underwent bilateral carotid intimectomy (5 cm long) and one side was seeded with an average of 2 x 10(6) viable freshly harvested endothelial cells. Blood flow was restored 20 min after seeding. On the contralateral side, a sham-seeding was performed. Deposition of 111indium-labelled autologous platelets was studied with sequential gamma camera images 3-5 h, 1, 2, 3, 4 days and 4 weeks after surgery. Platelet uptake was statistically reduced on the seeded side. Animals were killed at 4 weeks (nine dogs) and 5 weeks (four dogs) after surgery. Seven arteries for each group were found to be occluded. We conclude that endothelial cell seeding on endarterectomised arteries is feasible and reduces platelet uptake. Improvement in the efficiency of seeding and reduction of endothelial cell loss might permit clinical application of this technique. PMID- 1499742 TI - Storage in sodium chloride does not impair arterial prostacyclin release. AB - Heparinised sodium chloride solution is often used for the storage of veins and to prevent clotting in the arterial tree during vascular surgery. Sodium chloride deranges the morphology of endothelial cells and has therefore been interpreted as "toxic" to the endothelial cell. Perfused human saphenous veins and rabbit aortas show the same pattern of prostanoid release even though veins have a lower release than arteries. Excised rabbit aortas were stored in either (a) 0.9% sodium chloride or (b) 0.9% sodium chloride with heparin 5 I.U. ml-1 prior to being mounted in a perfusion model. The vessels were perfused ex vivo for 5 x 15 min with either Hanks' balanced salt solution (HBSS), calcium- and magnesium-free HBSS or 0.9% sodium chloride. For the last period, arachidonic acid (AA) 4 micrograms ml-1 was added. The release of prostacyclin, measured as the stable degradation product 6-keto-PGF1 alpha by radioimmunoassay, was not altered by storage in sodium chloride, or 0.9% sodium chloride plus heparin when compared with control segments. Perfusion with 0.9% sodium chloride did, however, significantly (p greater than 0.05) decrease the prostacyclin production when AA was added. This is most likely to be due to the low pH of the sodium chloride solution. It is concluded that short-term storage of rabbit aorta in sodium chloride plus heparin or 0.9% sodium chloride does not impair the prostacyclin cascade from the vessel wall, which might be of importance when choosing storage medium for reversed veins and veins used for coronary bypass surgery. PMID- 1499743 TI - Inflammatory aortic aneurysms: characteristic appearance on magnetic resonance imaging. AB - Ten to 15% of all aortic aneurysms show inflammatory change. They are characteristically covered on their anterior and lateral sides with thick white fibrous tissue. Peri-aortic fibrosis may spread into the retroperitoneum to encase and obstruct adjacent organs making operative treatment more difficult and increasing the operative morbidity and mortality. Fifteen patients with inflammatory aneurysms and 46 patients with simple non-inflammatory aneurysms were studied prospectively. Each patient underwent magnetic resonance imaging (MRI) using a Picker Vista MR2055 scanner operating at 0.5 tesla. Each scan was reviewed by a radiologist (G.G.H.) preoperatively and a diagnosis of inflammatory or non-inflammatory aneurysm made. At operation, the diagnosis of aneurysm type was made on macroscopic features of inflammatory change, and confirmed histologically using previously published criteria. The radiological diagnosis was found to correspond to the surgical and pathological diagnosis in all cases. In cases of inflammatory aortic aneurysm the aneurysm wall appeared laminated on MRI scan, showing three or more bright, high-signal layers. These appearances of inflammatory change are characteristic, and were present in all 15 patients with such aneurysms. There were no false positives among those patients with simple aneurysms, and no false negatives. Operative specimens of aortic wall were taken from four patients with inflammatory aortic aneurysms and four patients with simple non-inflammatory aortic aneurysms, and subjected to MRI scanning. The characteristic banding appeared only in the inflammatory aneurysm wall samples. Magnetic resonance imaging is a highly sensitive investigative technique for the detection of inflammatory aneurysms, showing characteristic changes. These changes are also seen in in vitro scans of wall samples from inflammatory aneurysms.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1499744 TI - Postural changes in femoral artery blood flow in normal subjects, patients with peripheral vascular occlusive disease and patients undergoing lumbar sympathectomy, measured by duplex ultrasound flowmetry. AB - Regulatory peripheral vasoconstriction occurs in response to lower limb dependency. In mildly ischaemic limbs these responses are retained but are lost in patients with rest pain. Previously used methods have inherent difficulties when applied during postural change. We studied orthostatic responses in 12 normal subjects (aged 22-74 years, median 52 years) and 16 patients (aged 21-83 years, median 48 years) with mild and severe peripheral vascular disease using a duplex ultrasound flowmeter. In the normal subjects the 60-s mean common femoral artery volume flow values (ml min-1 +/- S.D.) were 77 +/- 83; -78 +/- 116; -190 +/- 136 for elevation, dependency and standing respectively. For claudicants (n = 7) the values were 18 +/- 37; -112 +/- 123; -216 +/- 103, respectively. In rest pain patients (n = 9) the responses were reversed, being -252 +/- 124; 131 +/- 89 and 184 +/- 85. Significant differences were apparent between elevation, dependency and standing flows, in each of the three groups (all p less than 0.0001). The rest pain group displayed characteristically different responses compared with both normal subjects and claudicants, for each postural change (p less than 0.0001 in all cases). Investigation of the dependency response was undertaken in eight further patients with rest pain before and after lumbar chemical sympathectomy and a characteristic pre-sympathectomy response predicted the clinical outcome. PMID- 1499745 TI - Treatment of mycotic aneurysm of the aorta and its branches: the location determines the operative technique. AB - Twenty-seven patients with mycotic aneurysms of the aorta and its major branches were operated on between 1969 and 1991. There were 24 males and three females ranging in age from 6 to 84 years (mean age for adults 63 years). Sixteen of the 27 (59%) aneurysms were ruptured and in situ repair was undertaken in 20 (74%) patients. The mean follow-up was 5.8 years (range: 8 months to 16 years). Four patients (15%) died during the hospital stay and 23 survived. There were eight late deaths, two of which were a direct result of the aneurysm. The estimated 1- and 5-year survival rates were 62 and 36%, respectively. Extra-anatomic reconstruction is the method of choice for the majority of patients with mycotic aneurysm of the infrarenal abdominal aorta and iliac arteries. In situ repair after an extensive debridement of the aneurysmal wall and all infected tissue combined with antibiotic therapy is a satisfactory method of treating mycotic aneurysms of other locations, and for a highly selected group of patients with infrarenal mycotic aortic aneurysms. PMID- 1499746 TI - Popliteal embolectomy: does it still have a role? AB - The failure of a femoral embolectomy presents a difficult problem. The role of popliteal embolectomy in the subsequent management is still not clear. A study of 12 patients who underwent a secondary popliteal embolectomy is reported. Nine of the 12 patients had successful results in terms of limb salvage. The question that has to be addressed is the role of popliteal embolectomy as opposed to thrombolysis. Recent studies tend to favour the latter approach. It is concluded that if an embolectomy catheter will not pass or will not clear the distal segment, the surgeon should consider intraoperative thrombolysis or popliteal embolectomy prior to embarking on a bypass procedure. PMID- 1499747 TI - Hypothesis: why venous oedema causes ulcers and lymphoedema does not. PMID- 1499748 TI - Accidental intra-arterial injection in drug addicts. PMID- 1499749 TI - Bilateral mycotic axillary artery false aneurysms in an intravenous drug user: unsuspected broken needle-tips pose a risk to the treating personnel. AB - Mycotic false aneurysms due to local arterial injury from attempted intravenous injections in drug addicts are increasing in frequency. The high incidence of HIV and hepatitis B virus in parenteral drug users may present a considerable risk to the treating personnel. This paper reports the unsuspected presence of broken needle-tips in the subcutaneous tissues of an intravenous drug abuser, in association with bilateral mycotic aneurysms of the axillary arteries. Broken needle-tips have the potential to cause needlestick injury to the operating team and the nursing staff, with the associated risk of transmission of HIV and hepatitis B virus infection. The presence of broken needle-tips should be suspected in drug users presenting with false aneurysms associated with local arterial injection injury and a specific history of needle-breakage should be sought. Preoperative plain radiographs should be performed of the planned operative field to exclude the presence of such needle-tips. Any soft tissue swelling in the vicinity of a major artery in an intravenous drug abuser should be suspected of being a false aneurysm until proven otherwise and should prompt immediate referral to a vascular surgeon for investigation and management. PMID- 1499750 TI - Abdominal aortic aneurysmectomy in a renal transplant patient. AB - Standard surgical techniques were modified to allow continued perfusion of a renal allograft during resection of a large symptomatic abdominal aortic aneurysm. Neither hypothermic perfusion nor temporary bypass were employed. No alteration in renal function was observed and the patient remains well. Complex methods of renal allograft protection are probably unnecessary when transplant recipients undergo aortic reconstruction. However simple modifications or technique can substantially reduce renal ischaemic time and further add to the safety of the procedure. PMID- 1499751 TI - Thrombogenicity of collagen prostheses. PMID- 1499752 TI - The relevance of short saphenous incompetence. PMID- 1499753 TI - Atherosclerotic aneurysm of the deep femoral artery. PMID- 1499754 TI - [Current aspects of the mechanism of action of calcium antagonists in patients with diabetes mellitus]. AB - The review summarizes recent data about the use of calcium channel blockers for the treatment of cardiovascular complications in patients with diabetes mellitus. It is shown that disturbances of Ca ion homeostasis play an important role in the pathogenesis of such diabetic complications as cardiomyopathy, microangiopathy, hypertension and the use of modern calcium channel antagonists for their treatment seems to be quite justified. However, despite definite positive effects of such treatment, these drugs should be used with care, especially if combined with derivatives of sulphonylurea as activators of the beta-cell function. Calcium channel blockers may intervene in the mechanism of the activity of beta cells in which activation of the calcium channels is an obligatory link for triggering insulin secretion. Nevertheless, according to most of the authors, in such cases Ca antagonists can be recommended in moderate doses under continuous control of the hormonal status of the patient. PMID- 1499755 TI - [Age-related changes in inotropic effects of noradrenaline and acetylcholine on the myocardium of guinea pigs]. AB - The inotropic effects of noradrenaline (10(-7)-10(-5) M) and acetylcholine (10( 8)-10(-6) M) were studied in experiments carried out on preparations of the right atria and on papillary muscles of the right ventricle in adult (4-5 months) and old (18-24 months) guinea pigs. An age-related decrease in inotropic noradrenaline effects and the displacement of dose-effect relationships to the right was revealed. Similar changes of the dose-related effects of acetylcholine superfused against the background of noradrenaline action were observed. The direct inotropic action of the acetylcholine did not change with ageing. A lack of the essential atrial-ventricular differences in age-related changes in myocardial reactivity is apparently very significant for support of effective functional coupling of cardiac chambers in ageing. PMID- 1499756 TI - [Resonance oscillations in the human arterial system]. AB - The paper summarizes the results of the experiments aimed at obtaining sphygmograms of peripheral and carotid arteries with due regard to the values of longitudinal dimensions of body and extremities in healthy subjects. Mathematical equations expressing the fact that dicrotic waves recorded on sphygmograms are the reflections of blood eigentones coinciding with resonance oscillations have been derived. It is proved that at least two partial vibration systems oscillating with different own frequencies are present in human arteries. Conditions under which the resonance of constituent frequencies of pulsatile pressure waves and output waves in arteries occurs have been determined. From this point of view a new explanation for the well-known phenomenon of the pulsatile wave amplitude increase from the heart towards peripheric regions is proposed. PMID- 1499757 TI - [Functional and morphological characteristics of coronary vessels in varying degree of coronary perfusion]. AB - Limitation of coronary perfusion of different degree induces inhomogeneous changes in resistance of vessels in the hypoperfusing zone: an adequate dilatory regulatory reaction may be followed by an increase in resistance of the coronary vessels. An active component of diastolic coronary resistance used to analyze vascular reactions, rate and character of changes in resistance under conditions of coronary perfusion as well as histological and electron-microscopic estimation of the vascular wall state testify to reversibility and active character of the observed changes in coronary resistance including its increase. This increase is pathogenetically significant as it may induce further development of the coronary perfusion disorder. PMID- 1499758 TI - [Effect of vibration on gamma-aminobutyric acid metabolism in the brain in various functional conditions of the adrenal cortex]. AB - The low-frequency vibration during 30 min (20 Hz, A = 0.4 mm) has been studied for its influence on the level of components of the GABA system and dicarbonic ++amino acids in male rats at hypo- and hyperfunction of the adrenal cortex. It is shown that under these conditions of the experiment the GABA level and glutamate-decarboxylase activity increase. Hyperfunction of the adrenal cortex against the background of vibration causes a relatively less pronounced increase in the GABA content, than the vibration alone or against the background of inhibition of adrenocortical function in the organism. PMID- 1499759 TI - [The role of the endothelium in the vascular effects of vintoperol]. AB - The effects of vintoperol have been studied in the experiments on the vascular bed of femoral artery of 15 mongrel dogs under chlorazol-urethane narcosis and on isolated vascular preparations of rats. It is shown that ++de-endothelization of vascular bed using saponin and mechanical removal of endothelial stripes decreased the vasodilatation reaction and relaxation of stripes by 50-60% of the initial values. While infusing ventoperol (0.3 mg.kg-1 min-1) to ++de endothelized vascular bed, the blood flow increased by 18 +/- 5% as against 47 +/ 3.9% of the initial value under intact endothelium. Blockade of guanylate cyclase by methylene blue decreased blood flow under vintoperol action to 24 +/- 3.5%. The similar results are obtained in the experiments in vitro. After ++de endothelization of pulmonary artery++ the amplitude of relaxation of preactivated smooth muscles decreased vs. initial tone (21 +/- 3.7% vs. 56% +/- 5.3%). Inhibition of relaxation reaction of vascular stripe under vintoperol effect is also observed after treatment with gossypol, or methylene blue. Thus, endothelium is involved in the realization of vasodilating effect of vintoperol, its action being mediated by endothelium--derived relaxing factor. PMID- 1499760 TI - [Experimental substantiation of the possibility to obtain anti-Proteus plasma]. AB - The possibility to produce the anti-Proteus plasma is experimentally substantiated. It is determined that polyvalent Proteus antigen immunization permits producing blood immune preparation, that is the high-active anti-Proteus plasma. its antibodies belonging to the class of immunoglobulin G. The anti Proteus plasma in liquid (at t = 6 degrees divided by 2 degrees C) and in frozen (at t = 20 degrees-5 degrees C) forms retains the specific activity for 3 days and 6 months, respectively. PMID- 1499761 TI - [Effect of beta receptor blockaders on the status of the lysosomal system of peripheral blood neutrophils in rabbits with immobilization stress]. AB - The investigation carried out on mature rabbits under conditions of beta adrenoreceptors' blocking by obsidan has revealed that 12-hour immobilization caused neutrophilic leukocytosis in the peripheral blood, degranulation of neutrophils, increase of acid phosphatase activity. These changes occurred much earlier as compared with those in the control group were more pronounced and lasted for a less period of time. Consequently, beta-receptors are the necessary components in the formation of stress-syndrome under the influence of an +non infectious stressor. PMID- 1499762 TI - [Aging-related characteristics of the secretory response of the stomach to stimulation of its mechanoreceptors]. AB - Age peculiarities of the gastric secretory response to the mechanical stimulation have been studied in thirty-one healthy subjects aged 60-79 and ten healthy subjects aged 20-35 (a control group). The secretory response of the gastric glands to mechanical distention of the stomach with 600 ml of water is found to decrease with aging. No changes in gastrin concentration in plasma during balloon distention have been revealed, so this confirms the hypothesis that stimulation of acid secretion by distention is mediated by reflexes without participation of the gastrin mechanism. Distention of the stomach with 800 ml of water induces significant inhibition of the acid output in subjects aged over 60. The mechanism of this reaction is not clear yet and needs further investigation. PMID- 1499764 TI - [Effect of extremely low frequency magnetic fields on time-related pattern of metabolism of thiol groups and products of lipid peroxidation in the brain of mice]. AB - The influence of extremely low-frequency magnetic fields on lipid peroxidation products and total thiol groups in the brain of mongrel mice has been investigated. Certain changes in time organization and interrelation of the studied processes under the effect of the magnetic field depending on frequency are shown. PMID- 1499763 TI - [Participation of cholecystokinin and pentagastrin in the regulation of the liver blood supply and oxygen consumption]. AB - Cholecystokinin and pentagastrin cause predominantly the dilatation of mesenterial, intrahepatic arterial and portal vessels. The short-term amplitude expressed changes in the vascular blood flow followed by less intensive long-term ones are observed. The amplitude of short-term reactions in these vascular regions is different and depends on the place of hormone injections. Cholecystokinin and pentagastrin in the same series of experiments decrease and increase the oxygen consumption by the liver depending on its functional state. It is supposed that correction of the oxygen supply of hepatocytes by the action of pentagastrin is realized due to changes in the blood flow in the liver artery, and under the cholecystokinin effect it is made by the change of the oxygen extraction. PMID- 1499765 TI - [Diphasic effect of thyrotropin on the uptake and absorption of iodine-131 by thyroid cell culture]. AB - The studies were performed on the primary culture of thyroid cells of newborn pigs. It was shown that thyroid-stimulating hormone (TSH) within the first 12th of its action inhibited uptake and organification of iodine-131. A negative influence of TSH on 131I uptake was retained both with its simultaneous introduction into the culture medium and with 30 min interval as well as when conducting experiments on the 1st, 3d, 5th and 7th days of cultivation. Previous 72h incubation with TSH sufficient for activation of all the links of iodine transport caused an increase in 131I uptake and organification. PMID- 1499766 TI - [Biological mechanism of long-term effect of alternating electric field on the development of mice]. AB - The method of principal components has been used for the quantitative analysis of 50 histomorphological indices of physiological state of white mice males subjected to the action of the alternating electric field in dynamics of their postnatal development. The theoretical analysis of the results obtained permits supposing that the alternating electric field disturbs proliferation and differentiation under its chronic action on the organism of mammals. PMID- 1499767 TI - [Age-related characteristics of triglyceride, secondary lipid peroxidation products and alpha-tocopherol levels in the tissues of female rats]. AB - The content of triglycerides, secondary lipid peroxidation products and alpha tocopherol closely related by complex functional interactions has been studied in the blood plasma, erythrocytes, liver and brain of rat females of all the age groups. The results obtained confirm an essential difference of vitamin E content in the tissues of rat females as against that in tissues of males. It may be a result of susceptibility of these parameters to endocrinic effects and of a particular functional role of alpha-tocopherol in females. PMID- 1499768 TI - [Human biorhythms and their use in work physiology]. PMID- 1499769 TI - The determination of nitrate in cured meat products. A comparison of the HPLC UV/VIS and Cd/spectrophotometric methods. AB - A comparison of the traditional spectrophotometric method, with prior application of a reducing Cd column, and a high performance liquid chromatography method with an anion exchanging column for the determination of nitrate in spiced Spanish sausage, was carried out. Both methods demonstrated a high correlation. The chromatographic method proved more precise, reproducible and appropriate for routine work. PMID- 1499770 TI - Deoxynivalenol in wheat and maize flour reference materials. 2. Preparation and certification. AB - The preparation of four cereal reference materials (two wheat and two maize) and the certification of their 4-deoxynivalenol (DON) contents is described. The materials were prepared and certified within the BCR programme of the Commission of the European Community as part of a broad activity to improve accuracy and agreement of measurements of importance in food and agriculture. Reference material RM 379 was prepared from naturally contaminated wheat four blended with 'blank' material to achieve the desired DON content. The reference material RM 378 was prepared from naturally contaminated maize identified as containing approximately the desired DON content. Details are given of the milling, blending and packaging procedure, and the checks to ensure homogeneity and stability of the materials. The reference materials RM 396 and 377 were similarly prepared from the blank wheat and maize samples respectively. The certification exercise was carried out by five laboratories (with a further two to three laboratories providing supporting data) using a variety of extraction and clean-up procedures with either high performance liquid chromatography (HPLC) or gas chromatography (GC) as the determinative stages. Wheat RM 379 was certified as containing DON at a level of 673 +/- 21 micrograms/kg and wheat RM 396 as containing less than 50 micrograms/kg. Maize RM 378 was certified as containing DON at 425 +/- 38 micrograms/kg and maize RM 377 as containing less than 50 micrograms/kg. The materials are intended for the verification of methods used to determine DON in cereal samples. PMID- 1499771 TI - Alternative fatty food simulants for migration testing of polymeric food contact materials. AB - The amounts of substances migrating from plastics into foodstuffs with high fat contents are in most cases higher than in foodstuffs with water contents. This increase in migration commonly is due to the higher solubility of the migrating organic compounds in fat compared to water. The increase in migration is not necessarily due to an increase in the substance's diffusion coefficient due to interactions between the fat and the plastic as is often assumed. Ethanol is a good simulant for fatty foods because it has little interaction with many plastics, e.g. polyolefins, migrants are readily soluble in it, and because it is easy to work with analytically. The utilizable limits of ethanol and ethanol/water mixtures as food simulants are developed from the physical background of diffusion. The use of ethanol and ethanol/water mixtures is supported by published experimental migration results. PMID- 1499772 TI - A method for the determination of methyl carbamate and ethyl carbamate in wines. AB - A method is described for the simultaneous determination of methyl carbamate (MC) and ethyl carbamate (EC) in wines that is based on: (a) extraction of the sample with dichloromethane using an extraction tube or an alumina-Celite column, (b) concentration of the extract to a small volume, and (c) determination by gas liquid chromatography-thermal energy analyser (N-mode). The method is highly sensitive (1-2 ng/ml), accurate (recoveries greater than 80%), and precise (CV, 5 10%). Nineteen of 27 samples of wines analysed contained traces (up to 2.7 ng/ml) of MC, and most contained EC (up to 70 ng/ml). Wines treated in the laboratory with 200 ppm dimethyl pyrocarbonate (DMPC)-a cold sterilant recently approved for use in wines-indicated that such a treatment may increase the MC contents of the wines to 10 ng/ml. Additional studies suggested that formation of MC in DMPC treated wines is dependent on both pH and ammonia content of the wines. The identity of MC in a few selected samples was confirmed by gas-liquid chromatography-high resolution (10 K) mass spectrometry. The natural low levels of MC found in these wines are not considered to pose a risk to human health. PMID- 1499773 TI - Determination of butyltin, cyclohexyltin and phenyltin compounds in beers and wines. AB - Butyl- cyclohexyl- and phenyltin compounds were extracted from enzymically hydrolysed wine and beer samples with 0.05% tropolone in pentane. Methyl derivatives were made by Grignard reaction for determination by gas chromatography-atomic absorption spectrometry. Wine and beer samples contained less than 0.1 to 160 nl/ml of butyltins from an undetermined source of contamination. GC-MS confirmation of butyltins also detected phenyltin, and di- and tricyclohexyltin compounds at levels less than the GC-AAS based method detection limits of 0.05-0.13 ng Sn/mL. PMID- 1499774 TI - Determination of total non-sulphonated aromatic amines in soft drinks and hard candies by reduction and derivatization followed by high-performance liquid chromatography. AB - Utilizing elements of methodology developed previously for food colours, total free and bound non-sulphonated aromatic amines (NSAA) were determined in commercial samples of soft drink beverages and hard candies. Bound amines in the samples were reduced using sodium dithionite, then total NSAA were extracted into chlorofom, transferred to aqueous acid solution and diazotized with sodium nitrite before coupling with 2-naphthol-3,6-disulphonic acid, disodium salt (R salt). The coloured derivatives were analysed using reversed-phase ion pair high performance liquid chromatography (HPLC) and an absorbance detector set at 512 nm. Solid phase extraction cartridges were utilized for extraction and clean-up of the food colours present in the sample, and the concentration of each dye was determined quantitatively using HPLC and absorbance detector wavelengths of 426, 516 or 625 nm. Levels of total NSAA were compatible with those observed previously in food colours. Commercial soft drinks were found to contain (expressed in terms of total free plus bound NSAA in the beverage) 0.19-12.6 ng/ml of aniline, 0.83-8.25 ng/ml 1-naphthylamine and 0.62-1.12 ng/ml 2 naphthylamine. Levels of 0.66-9.15 ng/g of aniline and 2.48-10.6 ng/g 1 naphthylamine were found in commercial samples of hard candies. Bound NSAA in hard candies appeared to survive the manufacturing process. Recoveries averaged 96.9% for tartrazine and 89.6-97.2% for the bound amines when hard candies were prepared in the laboratory. PMID- 1499775 TI - The evaluation in the Ames test of the mutagenicity of tetrahydro-beta-carboline 3-carboxylic acids from smoked foods. AB - This paper reports the evaluation of five tetrahydro-beta-carboline carboxylic acids, formed from the interaction of woodsmoke carbonyls and tryptophan, for mutagenicity in the Ames test. Three of the compounds tested have been detected recently in smoked foods at levels in the micrograms/kg or mg/kg range. None of the compounds induced mutagenicity in TA 97, TA 98 or TA 100 strains of Salmonella typhimurium either with or without prior activation. However, tetrahydro-beta-carboline-3-carboxylic acid, and to a lesser extent 1-methyl tetrahydro-beta-carboline-3-carboxylic acid were toxic to the strains of Salmonella typhimurium used. The inability of these beta-carbolines to induce mutation contrasts markedly with the mutagenicity of some beta-carbolines found in grilled meat products. PMID- 1499776 TI - Who cares if they outlaw amalgam? PMID- 1499777 TI - I can do it myself. PMID- 1499778 TI - Practical gloving and handwashing regime for dental practice. AB - The debate concerning the re-use of gloves in dental practice continues, despite the fact that recent guidelines on cross-infection control recommend that a new pair of gloves should be used for each patient. Whichever policy for glove use is adopted, it is important to take the maximum possible precautions in hand care. This paper presents a practical regimen for hand/glove washing which is simple, quick and effective. The importance of establishing a hand-care regimen in dental practice is emphasised. PMID- 1499779 TI - The future of direct reimbursement plans. PMID- 1499780 TI - Openness provides privacy, efficiency. PMID- 1499781 TI - Swindled! PMID- 1499782 TI - Action steps to achieve practice growth. PMID- 1499783 TI - One moment, please. PMID- 1499784 TI - Opening Pandora's box? PMID- 1499785 TI - PPOs benefit dentists and patients. PMID- 1499786 TI - Multipurpose office is the "talk of Temecula". PMID- 1499787 TI - Be prepared for patients' questions on tooth whiteners. PMID- 1499788 TI - The gifts of dentistry. PMID- 1499789 TI - Coordinator enhances hygienists' efficiency. PMID- 1499790 TI - 1-800-dentist pools advertising dollars. PMID- 1499791 TI - Held hostage by AIDS. PMID- 1499792 TI - Billing insurers for heat-processed inlays and onlays. PMID- 1499793 TI - A collections tool dentists can smile about. PMID- 1499794 TI - Another useful option--health-care credit cards. PMID- 1499795 TI - Electronic claims filing shows dramatic growth. PMID- 1499797 TI - How to start a practice for $15,000. PMID- 1499796 TI - Losing patients? Don't blame it all on the recession. PMID- 1499798 TI - Have you found your key to overhead control? PMID- 1499800 TI - A break with tradition. PMID- 1499799 TI - To buy or not to buy. PMID- 1499801 TI - Can dentistry be a path to financial independence? PMID- 1499802 TI - The in-house laboratory decision. PMID- 1499803 TI - Invitation to crime. PMID- 1499805 TI - Patients accept the dental laser. PMID- 1499804 TI - A cost-saving fringe benefit. PMID- 1499806 TI - A winning approach to infection control. PMID- 1499807 TI - Dental advertising: vice or virtue? PMID- 1499808 TI - "Secrets" of selling a dental practice "by owner". PMID- 1499810 TI - The best incentive--cash! PMID- 1499809 TI - Selling a dental practice. PMID- 1499811 TI - Combining high tech and patient comfort. PMID- 1499812 TI - Dentists form group to cover for members. PMID- 1499813 TI - Is your income protected? PMID- 1499814 TI - Use both Nd:YAG and CO2 lasers. PMID- 1499815 TI - Philosophy enhancement through video technology. PMID- 1499816 TI - Doctors and dentists. PMID- 1499817 TI - Burnout: the persistent peril. PMID- 1499818 TI - Building a practice in 550 square feet. PMID- 1499819 TI - Gaining reimbursement for infection control. PMID- 1499820 TI - Presbyopia isn't just for Presbyterians. PMID- 1499821 TI - Is your insurance coverage up-to-date? PMID- 1499822 TI - Handling medical waste. PMID- 1499823 TI - A new tool for periodontics. PMID- 1499825 TI - Dental insurance: help or hindrance? PMID- 1499824 TI - Are you playing Russian roulette? PMID- 1499826 TI - A fun place for the kids. PMID- 1499827 TI - Building a continuous improvement program. PMID- 1499828 TI - How practices that are going places get there. PMID- 1499829 TI - A critical look at reciprocity. PMID- 1499830 TI - The importance of asset allocation. PMID- 1499831 TI - Study club creates more interest in implants. PMID- 1499832 TI - Lamellocyte differentiation in Drosophila larvae parasitized by Leptopilina. AB - The presence of Leptopilina heterotoma or Leptopilina boulardi eggs in the hemocoel of a Drosophila melanogaster larva induces the differentiation of lamellocytes, the blood cells that encapsulate foreign objects. L. boulardi eggs are encapsulated by the newly differentiated lamellocytes, but L. heterotoma eggs are not. The induced lamellocytes in host larvae with L. heterotoma eggs undergo the same destructive morphological changes as reported previously for lamellocytes present in melanotic tumor mutant larvae at the time of parasitization. Thus, the virus-like particles produced by the L. heterotoma female to protect its eggs from encapsulation do not block the differentiation of lamellocytes, but rather destroy lamellocytes whenever they are present in the hemocoel. PMID- 1499833 TI - Agglutinin activity in Pacific oyster (Crassostrea gigas) hemolymph following in vivo Vibrio anguillarum challenge. AB - Hemolymph from the Pacific oyster (Crassostrea gigas) contains lectins that agglutinate horse (Gigalin E) and human (Gigalin H) erythrocytes. The gigalins also agglutinate bacteria, including Vibrio anguillarum, and were adsorbed from oyster hemolymph at different temperatures by living, heat-killed, and freeze dried V. anguillarum cells. Baseline activities of the two gigalins were established by measuring their activities in oyster hemolymph over a period of 4 years. A normal distribution of Gigalin H activity (mean titer 139) was found, whereas the distribution of Gigalin E activity in the same samples was skew (mean titer 512). No covariance was observed between the two agglutinin activities. Increased lectin activity above this baseline was found in oysters exposed for varying time intervals to V. anguillarum at different seasons and temperatures over a period of 2 years. Such exposure resulted in an increase in activity (titer) of four- to nine-fold for Gigalin E and three- to seven-fold for Gigalin H when compared with controls, and in augmentation in the hemolymph of a protein with the same electrophoretic mobility as affinity-purified oyster lectins (gigalins). Challenge with either living or heat-killed bacteria resulted in a significant increase of Gigalin E activity, whereas results for Gigalin H were variable. Oysters challenged with bacteria were observed to filter normally with open shells during the experiments. Also, no increase was found in hemolymph calcium that could indicate anoxia following bacterial challenge (0.49 +/- 0.004 mg mL-1) compared to unexposed oysters (0.50 +/- 0.001 mg mL-1). Increase in the concentration of free amino acids in oyster hemolymph was observed following exposure to bacteria (15.05 mM) and anaerobiosis (13.51 mM) compared to controls (9.06 mM), and changes (in mol %) of individual amino acids differed considerably between hemolymph from animals challenged with bacteria and animals kept anaerobic. The augmented lectin activity in oyster hemolymph, following in vivo exposure to increased bacteria in the seawater, suggests their involvement in enhancing bacterial clearance and defense in the oyster. PMID- 1499834 TI - Characterization of anti-hapten antibodies generated in vitro by channel catfish peripheral blood lymphocytes. AB - Secondary in vitro stimulation of channel catfish peripheral blood lymphocytes with haptenated T-dependent antigen (TNP-KLH) elicited large numbers of hapten specific Ab-producing cells and relatively high levels (10-96 micrograms/mL) of TNP-specific Ab in the culture medium. These in vitro generated Abs were compared to in vivo generated Abs from the serum of the same fish with respect to covalent structure, affinity, and isotypic composition of heavy and light chains. SDS-PAGE analysis under both reducing and nonreducing conditions revealed that the in vitro Abs were structurally similar to the serum Abs. Similarly, in vitro pulse labeled Abs also exhibited the eight band profile characteristic of channel catfish serum Abs when run under nonreducing denaturing conditions. Scatchard analysis of equilibrium dialysis data revealed that the affinities of the culture and serum-derived Abs were quite similar, that is, exhibited association constants of approximately 2.0 x 10(6) M-1. However, it was routinely observed that the in vitro generated Abs exhibited somewhat fewer binding sites per molecule than those derived from serum. The use of murine monoclonal Abs specifically for different isotypes of channel catfish heavy and light chains demonstrated that the isotypic composition of the culture- and serum-derived fish anti-TNP Abs were similar; exceptions occurred with cultures producing lower levels of Abs. These results strongly suggest that channel catfish in vitro Ab responses closely reflect what normally occurs in vivo. PMID- 1499835 TI - Phorbol ester/calcium ionophore activate fish leukocytes and induce long-term cultures. AB - This study documents that phorbol ester (TPA) and calcium ionophore (A23187) in combination are potent mitogens for channel catfish peripheral blood leukocytes (PBL), stimulating both catfish T and B cells. Unlike T-cell responses to Concanavalin A (ConA), these responses to TPA/A23187 did not appear to require monocytes and were not strongly inhibited by low culture temperature. These results support the notion that catfish lymphocytes utilize the bifurcating phosphatidylinositol bisphosphate second-messenger system for transmembrane signaling during the activation process, as do mammalian lymphocytes. Furthermore, it was unexpectedly found that TPA/A23187 stimulation of normal catfish PBL reproducibly (greater than or equal to 95%) resulted in the generation of long-term leukocyte cultures that did not require restimulation or the addition of exogenous factors for continued proliferation. These TPA/A23187 induced leukocyte cultures were refractory to cloning and appeared to contain 10 40% monocytes and 50-80% putative T cells with no detectable B cells or neutrophils. PMID- 1499836 TI - Changes in the thymus and spleen of the turtle Mauremys caspica after testosterone injection: a morphometric study. AB - To confirm a possible role of sex hormones in governing the seasonal variations affecting the reptilian lymphoid organs, a morphometric analysis was carried out on the thymus and spleen of turtles, Mauremys caspica, intraperitoneally injected with a single dose of testosterone propionate (TP) at the third week of June when physiological levels of testosterone are low. At 4 and 6 weeks, control turtles show an apparent lymphocyte mobilization both from thymus and spleen with a decrease in the percentage of thymic cortex, numbers of cortical lymphocytes, and mitotic index, but increased numbers of medullary lymphocytes. In the thymic cortex of treated turtles, there is a decrease in the same parameters but they occur in the first 2 weeks, whereas the medullary lymphocytes also undergo reduction at 4 and 6 weeks. In addition, the number of reticuloepithelial cells per area unit decreases at 2 weeks in the thymic cortex of treated turtles. These results are discussed from the point of view of a biphasic effect of testosterone on turtle lymphoid organs: In the first weeks, the changes observed could be attributed to the high levels of testosterone; after 4 and 6 weeks, variations are dependent both on long-term effects of testosterone and on those induced by the high values of corticosterone occurring in summer. PMID- 1499837 TI - MHC dosage effects on primary immune organ development in the chicken. AB - Immune development in vertebrates is thought to be influenced by many factors including genotype. We used the Trisomic avian model to probe for influences of the major histocompatibility complex (MHC) on the development of the primary immune organs. Chickens were produced having two, three, and four copies of the MHC-encoding microchromosome. Studies of growth, immune organ development and structure, and lymphocyte populations were performed at three post-hatching time points. Chickens with three and four MHC copies (trisomic and tetrasomic) exhibited reduced overall growth and had smaller bursae and thymuses compared to disomic controls. However, the fold reductions in immune organ weights were much greater than for body weights. Histological analysis of the immune organs revealed dramatic alterations in follicular composition in tetrasomic bursae compared to disomic controls. No obvious alterations were observed in thymic and splenic histology of tetrasomics. Studies of organ lymphocyte numbers revealed a sharp reduction in bursal and thymic lymphocyte counts of trisomic and tetrasomic chickens. Based on these results, it appears that MHC dosage modulates, in a targeted fashion, the cellularity of the primary immune organs through an extended period in differentiation of B and T lymphocytes. PMID- 1499838 TI - Effects of AFB1 embryonic exposure on chicken mononuclear phagocytic cell functions. AB - Effects of embryonic exposure to aflatoxin-B1 (AFB1) on the postnatal development of chicken mononuclear phagocytic system function was examined. Single exposure of 6-d chick embryos to 0.1, 0.5, and 1 micrograms AFB1 in 10 microL acetone was employed. Control embryos received 10 microliters solvent and sham-treated controls included embryos with a hole in the egg shell with no compound added. Aflatoxin B1 exposure caused a dose-related increase in embryonic mortality. After hatch, no differences were observed in body weight gain among treatment groups. The incidence of circulating thrombocytes was reduced in chicks exposed to the highest AFB1 dose with enhancement in monocyte and lymphocyte cell populations. Birds exposed to 1 microgram AFB1 recruited fewer macrophages in the peritoneal cavity after i.p. Sephadex elicitation along with reduced substrate adherence potential of peritoneal exudate cells. Similarly, macrophages from 0.5 and 1 micrograms AFB1-treated birds had depressed phagocytic potential. These results suggest that long-term immune depression of macrophage-mediated functions can occur following embryonic exposure to AFB1. PMID- 1499839 TI - Purine metabolism and B-lymphocyte development in the chicken bursa of fabricius. AB - The activity of three enzymes involved in the salvage pathway of purine nucleosides--purine nucleoside phosphorylase (PNP), xanthine dehydrogenase (XDH), and hypoxanthine-guanine phosphoribosyl transferase (HGPRT)--was investigated in cellular fractions of the chicken bursa of Fabricius differentially enriched in epithelial cells or lymphocytes. Markedly increasing levels of PNP and XDH were observed along with the enrichment in epithelial cells together with a slight, though significant, decrease in HGPRT activity. By contrast, a dramatic fall in PNP and XDH activities was detected along with the enrichment in lymphocytes together with a slight, though significant, increase in HGPRT activity. This sharply different distribution of the three enzymes, all sharing hypoxanthine as a substrate, clearly indicates that lymphocytes preferentially channel hypoxanthine into the salvage and interconversion pathways, phosphorylating it to IMP, while epithelial cells rapidly catabolize such a purine base to uric acid. Moreover, epithelial cells, unlike lymphocytes, are able to retain high intracellular levels of both hypoxanthine and inosine. These results support the possibility that epithelial cells contribute to the normal development of bursal lymphocytes by supplying such actively proliferating cells with purine rings and at the same time by preventing them from accumulating potentially toxic high levels of purine nucleotides being able to rapidly eliminate excess hypoxanthine as uric acid from the bursa environment into the bloodstream. PMID- 1499840 TI - Ultrastructural localization of a soluble antigen in the chicken Harderian gland. AB - The relationship between plasma cells, macrophages, B and T cells, dendritic cells, and epithelium in the chicken Harderian gland have been studied by means of ultrastructural localization of the horseradish peroxidase following local immunization. After 5 d, peroxidase activity was found in vesicles located in macrophages and immature plasma cells. On day 7, peroxidase-antiperoxidase complexes were found in vesicles of the epithelial cells lining the secondary ducts and the acini, in the lumina of the ducts, and on the surface of lymphocytes located among these epithelial cells. Dendritic cells showing peroxidase activity on their surface were seen in the subepithelial lymphoid tissue and in the lymphoid follicles. On day 9, peroxidase activity was found as iccosomes on the surface of dendritic cells and lymphoblasts. These results indicate that immature plasma cells in the Harderian gland can take up antigen and may have a role in presenting it to T cells. Further, our results suggest that intraepithelial lymphocytes might be involved in antigen transportation from the epithelium to the subepithelial lymphoid tissue. PMID- 1499841 TI - Lectins in the hemolymph of a starfish, Asterina pectinifera: purification and characterization. PMID- 1499842 TI - Effect of bursectomy on serum levels of chicken complement component C1q. PMID- 1499843 TI - Formation of brown bodies in the coelomic cavity of the earthworm Eisenia fetida andrei and attendant changes in shape and adhesive capacity of constitutive cells. AB - The formation of brown bodies in the coelomic cavity may result from an aggregation of coelomocytes around offending foreign cells such as bacteria, gregarines, incompatible graft fragments, and altered self structures such as setae or necrotic muscle cells. The initial nodule rapidly increases in volume by aggregation of new coelomocytes and various waste particles. When a brown body has reached a diameter of 1-2 mm, its external cells flatten and lose their adhesiveness toward free coelomocytes or waste particles and its pigment rapidly darkens. Brown bodies play an important role in homeostasis. PMID- 1499844 TI - Thrombocytopenia in the HELLP syndrome is not due to platelet-associated IgG (PAIgG). AB - The presence of membrane-bound and circulating platelet-associated IgG (PAIgG) in nine pregnant women with hemolysis, elevated liver enzymes, and low platelet count (HELLP syndrome) was investigated. The reference group consisted of 21 patients with chronic idiopathic thrombocytopenic purpura (ITP). In the majority of patients with ITP, thrombocytopenia results from the binding of PAIgG to the platelet membrane with subsequent platelet destruction. In none of the patients with HELLP syndrome membrane-bound or circulating PAIgG was found. By contrast, membrane-bound and circulating PAIgG was detected in 15 of the 21 cases of chronic ITP (71.4%). These findings suggest that platelet destruction in patients with HELLP syndrome does not result from the binding of PAIgG to the platelet membrane. Therefore, the treatment of thrombocytopenia in this syndrome with immunosuppressants (e.g., corticosteroids), as in chronic ITP, does not seem appropriate. PMID- 1499845 TI - Monoclonal enzyme immunoassay measurement of estradiol and progesterone receptors in in vitro fertilization and spontaneous cycles. AB - So far, the few studies performed on endometrial steroid receptors in in vitro fertilization (IVF) cycles have been carried out by the dextran-coated charcoal (DCC) method. Despite widespread efforts to standardize the DCC assay method, assay results still vary and thus, data obtained in IVF cycles are controversial. In the present article, late luteal estradiol (E2) and progesterone (P) receptor (R) levels were measured by a new monoclonal enzyme immunoassay (EIA) method in endometrial samples obtained from 21 patients in an IVF program who received no embryo transfer (ET) after ovarian stimulation with follicle-stimulating hormone/human menopausal gonadotrophin/human chorionic gonadotrophin under pituitary suppression with buserelin. Plasma levels of E2, P and prolactin (PRL) were measured in three blood samples collected in the midluteal phase. Results were compared with those obtained in a control group of 21 spontaneous cycles. E2, P and PRL were significantly higher in stimulated than in spontaneous cycles. The level of E2R was decreased in endometrium in IVF stimulated cycles, but PR remained unchanged. PMID- 1499846 TI - The endometrial biopsy as a predictive factor of pregnancy rate in women with unexplained infertility. AB - To investigate whether or not there is any relation between endometrial morphology and subsequent pregnancy rate, 47 couples with unexplained infertility were followed up for 3 years after they had had an endometrial biopsy. Each woman had an LH-timed endometrial biopsy performed in the luteal phase of the cycle. The biopsy was dated chronologically according to the luteinizing hormone (LH) surge and histologically using morphometric criteria. None of the women received any form of treatment in the endometrial biopsy cycle. Of 47 women with unexplained infertility, 36 (76.6%) (Group I) had 'in phase' endometrial development and 11 (23.4%) (Group II) had retarded endometrium. Women with normal endometrial development had a higher pregnancy rate than women with retarded endometrial development (50% vs. 9%; P less than 0.02). The fecundability during treatment cycles was higher in Group I than in Group II (0.051 vs. 0.008; P less than 0.05). In women with 'in phase' endometrium, treatment increased the monthly probability of conception (0.051 vs. 0.006; P less than 0.001). A precisely timed endometrial biopsy should be considered as part of the investigations for women with unexplained reproductive failure, to help determine prognosis. PMID- 1499847 TI - Uterine horn replacement in the rat using denervated and devascularized jejunum. AB - In the hope of identifying suitable material for reconstructive tubal and uterine surgery, the authors have replaced a portion of the uterine horns of two groups of Wistar rats (n = 10) with normal (VAS group) or with denervated and devascularized jejunal grafts (NVAS group). All grafted horns stayed patent. No pregnancy was observed in the uterine horns operated on. The light microscopic appearance of the grafts was studied and compared by ANOVA. Three months after surgery in the VAS group, the number (51.4 +/- 9.5) and height (309.8 +/- 44.7 microns, P less than 0.05) of the villus, the Lieberkuhn cripts height (156.9 +/- 34.9 microns) and the number of goblet cells per cript (7.2 +/- 1.2, P less than 0.05) had decreased in relation to their corresponding control jejunal fragments (57.7 +/- 5.4; 345.1 +/- 18.0 microns; 192.2 +/- 40.8 micron; 12.4 +/- 1.9, respectively). Three months after surgery, the intestinal structure was maintained in the anastomosis areas of the NVAS group, therefore the mucus production of the jejunal-graft mucosa was not completely eliminated. No villus or crypts were observed, but a monostratified cubic-cell-type epithelium at the NVAS jejunal graft mid-portion, along 58.1 +/- 12.9% of the total length of the intestinal graft. Under this epithelium a connective tissue, like a non-glandular submucosa, was apparent. PMID- 1499848 TI - Rhabdomyoma of the vagina. AB - A case of vaginal rhabdomyoma in 35-year-old healthy woman is presented. The lesion, a pedunculated polyp measuring 1.2 cm in diameter, was located in the anterior wall of the vagina. This is an extremely rare entity that pursues a benign course. Light and immunohistochemical features are commented and selected literature briefly reviewed. PMID- 1499849 TI - Pregnancy in primary biliary cirrhosis. AB - A 34-year-old multigravid woman with symptomatic primary biliary cirrhosis (PBC) of the liver had a successful pregnancy. A healthy baby was born prematurely at 36 weeks of gestation. Six months prior to the conception of this pregnancy, stage III PBC had been diagnosed. Portal hypertension and liver cirrhosis had not developed. It is uncommon for pregnancy to occur in the presence of PBC. In the case presented, the outcome of pregnancy was good and the liver function had not been significantly affected by the pregnancy. PMID- 1499850 TI - Female circumcision. Female genital mutilation. World Health Organization. International Federation of Gynecology and Obstetrics (FIGO). PMID- 1499851 TI - Organization of perinatal care within the European community. AB - A survey on the infrastructure and organization of maternity and neonatal services in the European Community has been conducted within the framework of the European Community Concerted Action Project 'New Methods for Perinatal Surveillance'. Objectives were to provide a basis for comparative evaluation of perinatal studies, to achieve a better understanding of differences in national perinatal services and to identify problem areas in provision of perinatal care. Data concern general maternal statistics, structure of maternity services and organization of maternity and neonatal services. Similarities between the perinatal services of the countries surveyed outweigh local deficiencies in some aspects of care and organization. Information tabulated in this survey can serve as a stimulant to reach a better understanding of current health care for pregnant mothers and their newborns within the European Community. PMID- 1499852 TI - What cervical dilatation rate during active labour should be considered abnormal? AB - The present study tested the common notion of slow labour that only dilatation rates of 1 cm/h and above lead to normal (intervention free) delivery. We examined all primiparous spontaneous term labours cared for in our hospital over a 1 year period when a protocol for intervention in the case of slow dilation rate was not in place. Of 505 consecutive singleton labours, 105 (20.6%) progressed at an overall cervical dilatation rate of less than 1 cm/h. However, only those progressing at 0.5 cm/h and less (n = 52 or 10.3% of the total) had significantly increased rates of oxytocin usage and of caesarean section. The data suggest that there may be a more conservative definition of slow labour. PMID- 1499853 TI - Blood flow velocity waveforms of the middle cerebral artery and abnormal neurological evaluations in live-born fetuses with absent or reverse end diastolic flow velocities of the umbilical arteries. AB - We studied 37 fetuses with absent or reverse end-diastolic flow velocities (AREDFV) of the umbilical arteries with respect to the mode of delivery, fetal acidosis, resistance index of the middle cerebral arteries, and abnormal neurological evaluation at the time of discharge from the department of pediatrics. A control group with normal umbilical artery flow velocity waveforms was matched for gestational age. Fetuses with AREDFV were delivered almost exclusively by cesarean section, in most cases due to fetal distress. Metabolic changes with decreased base excess values were found more often in fetuses with AREDFV, but no difference could be detected with respect to severe fetal acidosis. The number of fetuses with abnormal neurological evaluations during the first 6 months of life was significantly higher in cases with AREDFV than in the control group. More than two thirds of the fetuses with AREDFV showed an abnormal blood flow velocity waveform of the middle cerebral arteries with elevated end diastolic flow velocities. The combination of extreme premature delivery before 28 weeks of gestation, severe idiopathic respiratory distress syndrome, and a resistance index of the middle cerebral arteries under the 5th percentile seems to be a risk factor for early neurological morbidity in fetuses with AREDFV. Premature delivery of fetuses with AREDFV--as we did during our study in order to prevent intra-uterine death or fetal asphyxia--should therefore be critically regarded in cases under 28 weeks of gestational age and abnormal flow velocity waveforms of the middle cerebral arteries. PMID- 1499854 TI - A practical approach to identification of susceptibility genes for IDDM. AB - Of all the common diseases that have a genetic component, IDDM is probably the most tractable to the experimentalist. Large numbers of nuclear multiplex families are available, which can be stored as permanent cell lines; diagnosis is relatively unambiguous; and a mouse strain, the NOD, spontaneously develops autoimmune IDDM similar to the human disorder. In addition, the resolution and accessibility of the human genome map has been revolutionized by the discovery and widespread application of the PCR, particularly the amplification of short, tandemly repeated segments of DNA called microsatellites, which display high levels of allelic polymorphism. With these reagents, the stage is set for dissection of the genetic factors that control the pathophysiology of IDDM. PMID- 1499855 TI - Ambulatory blood pressure in type I diabetes mellitus. Comparison to presence of incipient nephropathy in adolescents and young adults. AB - AMBP measurements were obtained at 20-min intervals during the day and at 60-min intervals during the night in 38 adolescents and young adults (12-25 yr old) with type I diabetes, and in 36 healthy, nondiabetic control subjects of comparable age. The group of patients with elevated AER (greater than 15 micrograms/min) had higher mean 24-h sBP, dBP, and BPB (defined as the prevalence of systolic readings greater than 130 mm Hg or diastolic readings greater than 85 mm Hg) compared with both the group of patients with type I diabetes and AER less than 15, and the control group. The normal diurnal variation in BP and BPB was observed in the control group and the group with type I diabetes and AER less than 15, whereas the nocturnal decrease observed in the group with type I diabetes and AER greater than 15 was not statistically significant. Elevations in AMBP of the patient group with AER greater than 15 were reflected in random BP measurements. Even though the mean random BP measurements of all groups were within the normal range for age, the mean random sBP and dBP of the type I diabetes patients with AER greater than 15 was higher than both the control group and the group with type I diabetes and AER less than 15. The GFR, determined by the clearance of 99Tc-DTPA, was associated negatively with measures of AMBP and AER in the group with AER greater than 15.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1499856 TI - Comparison of peripheral and portal (via the umbilical vein) routes of insulin infusion in IDDM patients. AB - Twelve subjects with insulin-dependent diabetes mellitus were treated using continuous subcutaneous insulin infusion (CSII) and intraportal insulin infusion (IPII) via the umbilical vein for 4 mo. Glucose control improved in both CSII and IPII groups, but a decrease in glucose and HbAIc was more rapid and more significant in the IPII group than in CSII, even though insulin requirement was lower during IPII than CSII (40 +/- 2 vs. 50 +/- 2 U/day, P less than 0.05). The insulin plasma fasting levels were different (88 +/- 10.7 in the IPII group vs. 263 +/- 23 pM in CSII, P less than 0.001). High plasma levels of lactate, pyruvate, alanine, cortisol, and growth hormone were decreased in both groups, with their full normalization only in the IPII group. Glucagon concentrations were low in both groups at the beginning of the study (30.0 +/- 4.1 in the CSII group and 32.3 +/- 1.8 ng/L in IPII); they were equalized to control values in the IPII group and were low in the CSII group at the study's end (46.0 +/- 3.7 in IPII vs. 31.7 +/- 3.1 ng/L in CSII, P less than 0.05. We conclude that intraportal administration of insulin via the umbilical vein at rates of 0.01 0.05 U.kg-1.hr-1 reduces plasma levels of glucose, three carbon precursors, cortisol, and growth hormone by a direct action on the liver, and the hepatic action of peripherally administered insulin is manifested only when the infusion rate is increased to 0.1-0.3 U.kg-1.hr-1.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1499857 TI - Variation in sorbitol accumulation and polyol-pathway activity in cultured human proximal tubule cells. AB - The polyol pathway is present in tissues of several organs where its activation may participate in the development of diabetic complications. We measured the accumulation of polyol-pathway intermediates in HPT cells isolated from 21 different human kidneys from nondiabetic individuals. When exposed to 27.5 mM glucose in the growth media, cells isolated from approximately 75% of individuals (accumulators) accumulated sorbitol within 1-4 days, whereas 25% (nonaccumulators) accumulated only negligible amounts, even when the period of exposure was extended to 2 wk. Surprisingly, measurement of the activities of the polyol-pathway enzymes showed no difference in the levels of either AR or SDH between accumulators and nonaccumulators, even when the conversion of galactose to galactitol was used to measure AR activity in intact cells independently of SDH. Measurement of sorbitol in the growth media indicated that nonaccumulators were not releasing sorbitol into the growth media. Fructose levels in the conditioned growth media were 4 times higher in the sorbitol-accumulating cells. Together, these results indicate that the tendency of cells from an individual to accumulate significant amounts of sorbitol may reflect the cells' ability to metabolize sorbitol in steps subsequent to the polyol pathway. PMID- 1499858 TI - A new method for quantification of islets by measurement of zinc content. AB - The ability to quantify the yield of pancreatic islet tissue after isolation is important for interlaboratory comparisons and for the assessment of islet yield prior to clinical transplantation. Because pancreatic islets contain a much higher concentration of zinc than other tissues, we investigated the analysis of zinc as a measure of islet tissue yield. Rat islets of standard diameter 250 microns were handpicked into samples containing 10-80 islets. The zinc content was measured by EAAS and showed a linear correlation with islet number. A zinc binding fluorescent dye, TSQ, was investigated as a way of simplifying the zinc measurement for routine use. Samples of 10-80 islets of 250 microns were sonicated in 3 ml zinc-free water, 0.18 mumol TSQ was added, and the TSQ-zinc fluorescence was measured at 480 nm. A linear correlation was observed. Exocrine contamination up to 50% barely affected the results. Islet zinc content also was shown to be correlated linearly with islet number for freshly isolated human islets. Measurement of zinc by TSQ fluorescence is a rapid, cheap, and objective measure of islet tissue content. PMID- 1499859 TI - Effects of oleate and insulin on glucose uptake, oxidation, and glucose transporter proteins in rat adipocytes. AB - We examined effects of Na oleate on glucose uptake, glucose transporter protein concentrations, and glucose oxidation in isolated adipocytes from fed rats. Na oleate increased basel 14C-glucose uptake in a dose-dependent manner (+42% with 1.0 mM, +79% with 2.8 mM Na oleate), but had no statistically significant effect on insulin-stimulated glucose uptake. Insulin (100 nM) resulted in a redistribution of GLUT4 protein concentration from the LDM fraction (-42%) to the PM fraction (+266%) but did not affect the distribution of GLUT1. Na oleate had no effect on basal or insulin-stimulated concentrations of GLUT1 or GLUT4 proteins in the PM or LDM fractions. Na oleate (2.8 mM) had no statistically significant effect on basal glucose oxidation, but inhibited insulin-stimulated glucose oxidation by 48% (P less than 0.01). In summary, Na oleate inhibited insulin-stimulated glucose oxidation and stimulated basal glucose uptake in isolated adipocytes without affecting PM or LDM distribution of GLUT1 or GLUT4 proteins. We conclude that the stimulatory effect of Na oleate on basal glucose uptake in adipocytes may be mediated by changes in the intrinsic activity of the glucose transporters. PMID- 1499860 TI - Noninvasive detection of cardiac sympathetic nervous dysfunction in diabetic patients using [123I]metaiodobenzylguanidine. AB - The association between clinical autonomic dysfunction and myocardial MIBG accumulation was investigated. The study groups comprised 6 male diabetic patients with autonomic neuropathy (ANP+ group), 6 male diabetic patients without autonomic neuropathy (ANP-group), and 6 male nondiabetic control subjects. The mean age was comparable in all groups, and the subjects had no evidence of coronary heart disease. Reduced heart-rate variation in a deep-breathing test was used as a criterion for autonomic neuropathy. Immediately after injection, the peak net influx rate of MIBG to myocardium was significantly (P less than 0.05) reduced in both diabetic groups. At 6 hr after MIBG injection, the MIBG uptake of the myocardium was significantly (P less than 0.05) smaller in the ANP+ group than in the control group. In the ANP- group, the MIBG uptake of the myocardium was between that of the ANP+ group and that of the control group. Our data show that reduced myocardial MIBG accumulation is associated with autonomic dysfunction in diabetic patients, but it can occur to a lesser extent also in diabetic patients without apparent autonomic neuropathy. The measurement of the myocardial MIBG accumulation is a promising new method to detect cardiac sympathetic nervous dysfunction in diabetic patients. PMID- 1499861 TI - Impaired insulin-mediated skeletal muscle blood flow in patients with NIDDM. AB - Patients with non-insulin-dependent diabetes mellitus (NIDDM) exhibit decreased rates of skeletal muscle insulin-mediated glucose uptake (IMGU). Because IMGU is equal to the product of the arteriovenous glucose difference (AVG delta) across and blood flow (F) into muscle (IMGU = AVG delta x F), reduced tissue permeability (AVG delta) and/or glucose and insulin delivery (F) can potentially lead to decreased IMGU. The components of skeletal muscle IMGU were studied in six obese NIDDM subjects (103 +/- 9 kg) and compared with those previously determined in six lean (weight 68 +/- 3 kg), and six obese (94 +/- 3 kg) with normal glucose tolerance. The insulin dose-response curves for whole body and leg muscle IMGU were constructed using the combined euglycemic clamp and leg balance techniques during sequential insulin infusions (range of serum insulin 130-80,000 pmol/L). In lean, obese, and NIDDM subjects, whole body IMGU, femoral AVG delta, and leg IMGU increased in a dose-dependent fashion over the range of insulin with an ED50 of 400-500 pmol/L in lean, 1000-1200 pmol/L in obese, and 4000-7000 pmol/L in NIDDM subjects (P less than 0.01 lean vs. obese and NIDDM). In lean and obese subjects, maximally effective insulin concentrations increased leg blood flow approximately 2-fold from basal with an ED50 of 266 pmol/L and 957 pmol/L, respectively (P less than 0.01 lean vs. obese). In contrast, leg F did not increase from the basal value in NIDDM subjects (2.7 +/- 0.1 vs. 3.5 +/- 0.5 dl/min, NS).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1499862 TI - A rapid and sensitive radioimmunoassay for the measurement of proinsulin in human serum. AB - RIA methodology is used widely to measure proinsulin in human serum. However, some RIAs lack the sensitivity necessary to quantify proinsulin in unextracted serum and require long incubation periods. We developed an RIA with a sensitivity of 3.5 pM that permits the routine measurement of proinsulin in less than 48 h. This was accomplished by using a nonequilibrium binding reaction at room temperature and PEG-assisted second antibody precipitation as the method for separating bound and free proinsulin. We obtained a specific antiproinsulin antibody by absorbing the initial goat antiserum with human C-peptide-agarose. Proinsulin produced 50% displacement of tracer at 25.6 pM, whereas both human insulin and C-peptide failed to displace tracer at concentrations as high as 1 microM. We evaluated several cleaved derivatives of proinsulin for cross reactivity with the antibody. B-chain-C-peptide cleaved derivatives (less than or equal to 50% cross-reactivity) were more potent than A-chain-C-peptide cleaved derivatives (less than 5% cross-reactivity). However, all derivatives cleaved in the region from 56-60 failed to cross-react with the antiserum. These data indicate that a major antigenic determinant is present on the C-peptide region of proinsulin adjacent to the A-chain-C-peptide junction. After administration of an oral glycemic challenge, the mean fasting serum concentration of proinsulin in normal adults rose from 4.1 +/- 0.28 to 23.6 +/- 3.8 pM. We found a significant difference in the proinsulin concentrations in 6 adults before and after a glycemic challenge when two different antibodies were used in the RIA.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1499863 TI - Diminished glomerular capillary hydraulic conductivity precedes morphologic changes in experimental diabetes mellitus in the rat. AB - Glomerular ultrafiltration coefficient, Kf, is diminished in established diabetic nephropathy. To determine whether Kf is decreased because of a decrease in capillary area, A, and or in hydraulic conductivity, Lp, glomerular Kf and morphometric parameters were measured, and Lp was calculated in glomeruli of young rats with STZ-induced DM and in control rats. STZ was administered to Fischer 344 rats that weighted 50-75 g; glomeruli were examined after 3 or 5 mo of DM, and their structure and function was compared with that of control rats. The effects of insulin or of an ACEI, enalapril, also were assessed after 3 or 5 mo. Growth of DM rats was markedly impaired, and their ratio of kidney weight to body weight was increased. Ccr was proportional to rat weight, and the ratio of Ccr to body weight was not different in DM and control rats. At 3 mo, average volume of glomeruli isolated from DM rats was less than that of glomeruli from control rats. In contrast, glomerular volume after 5 mo was equal in DM and control rats. No increase in GBM thickness or mesangial volume was observed, nor was any decrease seen in GBM area in DM rats at 5 mo. Kf was lower in DM rats than controls after 3 mo, but not after 5 mo. The Lp of DM and control glomeruli did not differ at 3 mo, but was lower in DM at 5 mo. Insulin therapy improved somatic growth and increased kidney and glomerular size in DM rats; the kidney weight/body weight ratio remained elevated.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1499864 TI - Growth of neonatal islet transplants in the spontaneously diabetic BB/Wor rat. AB - We have previously shown that culture-isolated neonatal islets are able to survive both rejection and the recurrence of autoimmunity in the spontaneously diabetic BB/Wor rat. In trials designed to demonstrate the MHC restriction of the autoimmune response in this model, we discovered that neonatal islet grafts from diabetic BB rats appeared larger than grafts from nondiabetic controls. This study was undertaken to quantify the mass difference seen in this original study and to determine the characteristics of graft growth in more highly controlled trials. Grafts from diabetic animals in the original study were significantly larger than those from nondiabetic animals (81 +/- 36 vs. 238 +/- 216 micrograms, P = 0.01). These findings were supported by results from a second series of experiments, in which the mean growth index of grafts from diabetic animals was 7.25 +/- 4.91, whereas that from nondiabetic animals was 2.5 +/- 1.15 (P = 0.011). Three animals in this study were reversed of hyperglycemia: two had normal and one had a subdiabetic ip GTTs. These three rats received 97, 317, and 408 micrograms of islet tissue that increased in mass to 1790, 3270, and 4107 micrograms, respectively. Nuclear/total cell area percentages were the same in diabetic and nondiabetic grafts (P = 0.76), suggesting that the increase in mass was attributable primarily to proliferation rather than hypertrophy. Limited studies that use BrDU incorporation support this conclusion.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1499865 TI - Insulin treatment, endogenous insulin concentration, and ECG abnormalities in diabetic Pima Indians. Cross-sectional and prospective analyses. AB - The prevalence and incidence of CHD, defined by ECG abnormalities according to the Tecumseh criteria for Minnesota Codes, were determined in Pima Indians greater than or equal to 25 yr of age. In a cross-sectional analysis, the age-sex adjusted prevalence (+/- SE) of ECG abnormalities was higher in 1454 NIDDM patients (6.86 +/- 0.65%) than in 1696 nondiabetic subjects (3.23 +/- 0.63%; prevalence rate ratio = 2.12; 95% CI 1.39-3.25). In a prospective analysis, the age-sex-adjusted incidence (+/- SE) of ECG abnormalities was higher in 824 NIDDM patients (12.77 +/- 1.67) than in 935 nondiabetic subjects (5.93 +/- 1.43 cases/1000 person-yr; incidence rate ratio = 2.15; 95% CI 1.26-3.69). The prevalence of ECG abnormalities in insulin-treated NIDDM patients was significantly higher than in NIDDM patients not treated with insulin (age-sex adjusted OR = 2.83; 95% CI 1.84-4.33); and this association persisted when adjusted for other factors such as sBP, BMI, duration of diabetes, serum cholesterol concentration, and oral hypoglycemic agents (OR = 2.12; 95% CI 1.34 3.37). In the prospective analysis, the incidence of ECG abnormalities in NIDDM patients treated with insulin was higher than in those NIDDM patients not treated with insulin, but, when controlled for age, sex, duration of diabetes, and oral hypoglycemic agents in a proportional-hazards model, the relationship with insulin treatment was not statistically significant (incidence rate ratio = 1.36; 95% CI 0.80-2.31). This suggests that insulin treatment may be a marker of more severe diabetes, and that factors associated with clinical indications for insulin treatment, rather than insulin treatment per se, are related causally to CHD. On the other hand, endogenous fasting and 2-h postload serum insulin concentrations were not associated with ECG abnormalities among 761 NIDDM patients not treated with insulin nor among 1226 nondiabetic subjects. Furthermore, in the prospective study, neither endogenous fasting nor 2-h postload serum insulin was associated with the subsequent development of ECG abnormalities in NIDDM patients or nondiabetic subjects. PMID- 1499866 TI - Total body fat content and fat topography are associated differently with in vivo glucose metabolism in nonobese and obese nondiabetic women. AB - In this study, total body fat content and fat topography were related to glucose metabolism in the basal and insulin-stimulated states in 18 nonobese and 18 obese premenopausal nondiabetic women. All subjects received a euglycemic insulin (20 mU.min-1.m2) clamp study in combination with [3-3H]-D-glucose infusion and indirect calorimetry to quantitate total body glucose uptake, glucose oxidation, and nonoxidative glucose disposal. Total body fat content was determined with tritiated water, whereas body fat distribution was estimated from the WHR, the STR, and the VSR (measured by magnetic resonance imaging). In the postabsorptive state, total body glucose utilization, glucose oxidation, and nonoxidative glucose disposal rates were similar in nonobese and obese women, whereas during the insulin clamp all three metabolic parameters were reduced significantly in the obese group. In nonobese women, total body fat content was related inversely to both total and nonoxidative glucose disposal during the insulin clamp, whereas no relationship was found between glucose metabolism (total, oxidative, and nonoxidative) and WHR, STR, or VSR. In contrast, in obese women, no relationship was observed between total body fat content and any measure of insulin-mediated glucose metabolism. However, both WHR and VSR were related inversely to total, oxidative, and nonoxidative glucose disposal rates during the insulin clamp. These results suggest that total body fat content and body fat topography are associated differently with insulin-mediated glucose metabolism in nonobese and obese women. In the nonobese women, total body fat mass appears to be a primary determinant of tissue sensitivity to insulin, whereas in obese women, body fat topography exerts a more dominant effect. PMID- 1499867 TI - Identification and characterization of aldose reductase in cultured rat mesangial cells. AB - Although the enhanced activity of the polyol pathway has been detected in diabetic glomeruli, the intraglomerular localization of this pathway has not yet been well defined. In this study, we attempted to identify aldose reductase, a key enzyme of the polyol pathway, in cultured rat mesangial cells and to characterize the properties of this enzyme using enzymological and immunological methods. When the aldose reductase (DL-glyceraldehyde-reducing) activity was analyzed in mesangial cell extract, the Lineweaver-Burk plot showed concave downward curvature, and the Michaelis constant was 0.83 mM DL-glyceraldehyde, and this activity was noncompetitively inhibited by an aldose reductase inhibitor, ICI-128,436. The enzyme activity was enhanced by the addition of sulfate ion and partially suppressed by barbital. The enzyme cross-reacted with the antisera against rat lens and testis aldose reductases on Ouchterlony plate, and migrated to the region of molecular weight of about 36,500 Da on Western blotting. The presence of aldose reductase mRNA was also confirmed by Northern analysis using cDNA for rat aldose reductase, 10Q. From these results, it was concluded that the aldose reductase may exist in rat glomerular mesangial cells and may play a role in the development of diabetic glomerulopathy, though the coexistence of aldehyde reductase(s) may not be fully ruled out. PMID- 1499868 TI - Markedly reduced beta-cell function does not result in insulin resistance in islet autografted dogs. AB - Autotransplantation of islets of Langerhans has resulted in long-term normoglycemia in pancreatectomized dogs. This canine model is useful in evaluating both the progress of islet transplantation and the effect of a reduced islet mass upon the determinants of glucose tolerance: i.e., insulin secretion, insulin sensitivity, and glucose effectiveness. To determine the effect of a reduced islet mass on these factors, we measured the acute insulin response to arginine (AIRa) and glucose (AIRg), the slope of glycemic potentiation of AIRa (SP), insulin sensitivity (Sl), and glucose effectiveness (SG) in control (CN), diabetic (DM), and pancreatectomized dogs rendered normoglycemic with transplanted autografts of islets of Langerhans (TX). Normal fasting plasma glucose (FPG) (TX 4.7 +/- 0.2 mM; CN 4.9 +/- 0.1 mM; P greater than 0.05) was maintained despite a markedly reduced insulin secretion in TX (AIRa 24%, AIRg 15%, and SP 11% of CN). All measures of insulin secretion were significantly correlated (SP vs. AIRg, r = 0.80, P less than 0.0001; AIRa vs. AIRg, r = 0.92, P less than 0.0001) across all animals, but none of the measures of secretion were significantly correlated with either the number of islets transplanted or time posttransplant (P greater than 0.10). Insulin sensitivity was normal in islet autografted dogs (TX: 136 +/- 12 min-1/(nmol/ml); CN: 101 +/- 11 min-1/(nmol/ml), P greater than 0.05) but SG was reduced (TX: 1.93 +/- 0.28 x 100 min-1; CN: 3.53 +/- 0.35 x 100 min-1, P less than 0.05), as determined by the minimal-model method. In diabetic animals (FPG = 16.1 +/- 1.3 mM), insulin secretion was negligible by all measures (P greater than 0.05), and was associated with insulin resistance (Sl = 28 +/- 8 min-1/(nmol/ml)) and reduced SG (1.72 +/- 0.11 x 100 min-1). These studies indicate that across a range of insulin secretion in dogs, the secretagogues arginine and glucose provide similar estimates of beta-cell function. This markedly reduced beta-cell function does not result in insulin resistance when fasting normoglycemia is maintained, but is associated with a decrease in glucose action at basal insulin. PMID- 1499869 TI - An ELISA for antibodies to recombinant glutamic acid decarboxylase in IDDM. AB - To detect serum antibodies to GAD in subjects with IDDM, three recombinant mBGAD 67 peptides encompassing the full-length protein were used in an ELISA. In this study 7 of 9 (78%) preclinical IDDM subjects (ICA+ first-degree relatives of a person with IDDM) and 6 of 13 (46%) recent-onset IDDM subjects, but no subjects with Graves' disease (n = 10) or scleroderma (n = 10), nor healthy nondiabetic control subjects (n = 10) had antibodies that reacted with one or more of the recombinant mBGAD peptides. We found no preferential reactivity with any recombinant peptide. Although only 3 preclinical subjects and 1 recent-onset subject had antibodies to all three mBGAD peptides, the results indicate that mBGAD 67 contains at least three B-cell autoepitopes. Compared with an immunoprecipitation assay of native human brain GAD, the ELISA detected 5 of 6 (83%) preclinical and 6 of 6 (100%) recent-onset IDDM subjects. The ELISA should facilitate screening to evaluate the role of autoimmunity to GAD in the development of IDDM. PMID- 1499870 TI - Banting Lecture: glucose turnover. A key to understanding the pathogenesis of diabetes (indirect effects of insulin). AB - This article is divided into two parts. A retrospective overview summarizes some of the work that provided the framework and tools of the more recent studies. The five novel areas of research are related to the indirect effects of insulin. Regulation of plasma glucose is of central importance in health and diabetes. Understanding this precise regulation requires sensitive isotope dilution methods that can measure the rates at which glucose is produced by the liver and used by the tissues on a minute-to-minute basis. Validation studies indicated that the non-steady-state tracer method yields reasonable results when the specific activity of plasma glucose does not change abruptly. During hyperinsulinemic glucose clamps, the decrease in specific activity of glucose can be prevented by the MSTI. During exercise, the decrease of specific activity can be only in part ameliorated by step-tracer infusion. Depancreatized dogs are used extensively as a model of selective insulin deficiency, because dog stomach secretes physiological amounts of glucagon. This strategy can avoid injections of somatostatin, which can have other affects in addition to the suppression of insulin and glucagon. In human diabetes, in addition to an increase of glucose production, there is also an increase in glucose cycling in the liver. In animal models of diabetes, mild NIDDM, and in glucose intolerance, the percentage of increments of glucose cycling are much larger than those of glucose production. We hypothesize, therefore, that measurements of glucose cycling can be used as an early marker of glucose intolerance. Application of different tracer strategies and use of the depancreatized dog as a model of diabetes, we investigated the importance of the indirect effects of insulin in the pathogenesis of diabetes. 1) Because, in the treatment of IDDM, insulin is administered by the peripheral routes we compared the relative importance of hepatic and peripheral effects of insulin in regulating the rate of glucose production. Experiments were performed in depancreatized dogs that were initially maintained at moderate hyperglycemia (10 mM) with subbasal portal insulin infusion. During the experimental period, insulin was infused either peripherally or portally at 0.9 mU.kg-1.min-1. In addition, peripheral infusions were also given at 0.45 mU.kg-1.min-1. We concluded that when suprabasal insulin levels are provided to moderately hyperglycemic depancreatized dogs, the suppression of glucose production is more dependent on peripheral than portal insulin concentrations. This indirect effect of insulin may be mediated by limitation of the flow of precursors and energy substrates for gluconeogenesis and/or by suppressive effect of insulin on glucagon secretion.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1499871 TI - Lilly Lecture: syndromes of insulin resistance. From patient to gene and back again. AB - The syndromes of insulin resistance are a group of clinically diverse disorders, and our understanding of their molecular pathogenesis has advanced in parallel with our understanding of the structure of the insulin receptor and the mechanism of insulin action. The most straightforward progress has related to defining the role of both anti-receptor antibodies and mutations in the insulin receptor gene in causing these disorders. Despite this progress, the cause of severe target cell resistance in patients without defects in the receptor locus remains unknown, and we are limited in our ability to relate specific molecular defects in insulin signalling to in vivo phenotypes, such as those relating to growth and development and function of adipose tissue and muscle. Answers to these questions may ultimately be explained by the existence of multiple species of insulin receptors expressed in different tissues, brought about by alternative splicing and receptor hybrids, and by divergent pathways of insulin signalling with different consequences for specific tissues. The possibility that the insulin receptor and GLUT4 may be candidate genes for inherited insulin resistance in NIDDM has been addressed with the aid of genetic screening techniques such as SSCP. Currently, the loci have not been implicated in studies in most patients. Transgenic methodologies will be powerful tools for pursuit of unanswered questions in the field of insulin resistance in coming years. PMID- 1499872 TI - Influence of pirenzepine on gallbladder contraction in man induced by sham feeding or an intraduodenal meal. AB - Pirenzepine, an M1 muscarinic receptor antagonist, was tested for its ability to antagonize sham feeding- and intraduodenal fatty meal-stimulated gallbladder contraction in man. Intravenously administered pirenzepine abolished sham feeding induced gallbladder contraction. Pirenzepine also inhibited contraction induced by intraduodenal meal, but this inhibition was of a lesser magnitude than the inhibition of sham feeding-induced contraction. The results demonstrate that the cephalic phase of gallbladder contraction is probably mediated by M1 muscarinic receptors while the duodenal phase of gallbladder contraction is partially mediated by M1 receptors. PMID- 1499873 TI - Gastric and colorectal cancer in the rural Indian subcontinent: a survey of patients attending mission hospitals. AB - 37 missionaries working in India, Nepal, Pakistan, Bangladesh and Bhutan completed questionnaires regarding their clinical practice during the year 1980. Information was collected on the frequency of both gastric and colorectal cancers. More than 500,000 out-patients were reviewed and over 100,000 inpatients treated. A total of 291 gastric tumours and 169 colorectal carcinomas were diagnosed. Surgery was performed in 82% of the hospitals but only 36% had a histology service. In India and Pakistan there was no significant difference between the incidence of gastric and colorectal neoplasms. The relative risk of developing gastric rather than colorectal cancer in Bangladesh was 8 (95% confidence limits 4.5-14.2) and in Nepal the relative risk was 4 (95% confidence limits 2.0-7.0). A significant variation in the occurrence of cancer was observed between countries. Nepal had the highest and Pakistan the lowest numbers of both gastric and colorectal tumours. It seems likely that local environmental factors, such as diet, play a significant role in the development of these tumours. PMID- 1499874 TI - Repeated upper gastrointestinal hemorrhage caused by metachromatic leukodystrophy of the gall bladder. AB - A 27-year-old man with metachromatic leukodystrophy (MLD) of the adult type had developed repeated severe gastrointestinal (GI) bleeding. During endoscopic retrograde cholangiography (ERC), hemobilia was observed on two occasions. The definite diagnosis was obtained by a biopsy specimen taken from the lumen of the gall bladder during ERC, demonstrating large masses of metachromatic material inside the gall bladder. Upon cholecystectomy, papillomatosis of the gall bladder was found virtually obliterating the lumen of the gall bladder. A blood clot was observed at the angle of the cystic duct; histologic examination revealed diffuse hemorrhage into the stroma of the gall bladder. The patient is without upper GI hemorrhage since 3 years. In patients with MLD and upper GI bleeding, one should, therefore, be aware of the gall bladder as a possible source of hemorrhage. PMID- 1499875 TI - Multicenter double-blind trial of gabexate mesylate (FOY) in unselected patients with acute pancreatitis. AB - A multicenter, randomized, double-blind trial was carried out to evaluate the efficacy of gabexate mesylate (FOY) in acute pancreatitis. One hundred unselected patients were randomly allocated into two groups: 51 were assigned to receive FOY (12 mg/kg/day as continuous intravenous infusion for a minimum of 4 days and a maximum of 12 days), and 49 were allocated to placebo. The groups were comparable in demographic, clinical and biochemical parameters, etiology of pancreatitis, and disease severity, which was generally mild. Gallstones were the main etiological factor. All patients received fluid and electrolyte replacement, analgesia and nasogastric suction for at least 48 h after admission. Experimental therapy was initiated no later than 12 h after the beginning of symptoms. The results showed no statistically significant differences between the two groups with respect to the evolution of clinical and biochemical parameters, analgesic requirements, development of complications, hospitalization time or mortality at completion of the trial. In conclusion, early treatment with FOY does not appear to have any demonstrable beneficial effects in acute pancreatitis. PMID- 1499876 TI - Human gastric alcohol dehydrogenase: in vitro characteristics and effect of cimetidine. AB - The presence of at least two types of alcohol dehydrogenase has been demonstrated in surgical specimens from the human stomach. One isoenzyme has a Km of approximately 1-2 mM for ethanol comparable to that of class I alcohol dehydrogenase isoenzyme as defined for the liver. This isoenzyme can also be detected by immunohistology using a polyclonal rabbit antibody against human liver class I alcohol dehydrogenase. The other isoenzyme of alcohol dehydrogenase has a much lower affinity to ethanol (greater than 300 mM), but with activities that become significant at ethanol concentrations of more than 100 mM commonly present in the human stomach. Cimetidine was found to be a noncompetitive inhibitor of gastric alcohol dehydrogenase at concentrations as low as 1 mM in vitro. Since the human gastric alcohol dehydrogenase is responsible for the first pass metabolism of ethanol, its inhibition by cimetidine may explain the reduced first-pass metabolism of alcohol which is associated with elevated ethanol blood concentrations seen after cimetidine therapy. PMID- 1499877 TI - Prevalence of pancreatitis in liver diseases of various etiologies: an analysis of 107,754 adult autopsies in Japan. AB - The frequency of acute and chronic pancreatitis is 3.3 and 2.1%, respectively, in 107,754 adult autopsies in Japan. Acute pancreatitis is highly associated with liver diseases of various etiologies such as subacute hepatitis (16.1%), fulminant hepatitis (13.5%), biliary cirrhosis (10.5%), cholangiocarcinoma (8.6%) and postnecrotic cirrhosis (7.1%). Chronic pancreatitis is also closely related to various liver diseases. It is suggested that the portal venous stasis in liver diseases may predispose the patients to develop pancreatitis regardless of the etiology of liver diseases. PMID- 1499878 TI - Intermediate filaments and epithelial differentiation of male rat embryonic gonad. AB - The presence and distribution of desmin, vimentin, cytokeratin, and laminin in the gonads of developing male rat embryos (11-17 days) were studied by immunocytochemistry. The findings were correlated with morphological changes of the cells and with the formation of basement membranes, as determined by electron microscopy. The surface epithelial and subepithelial cells of the meesonephros in the prospective gonadal region contained desmin. At the onset of gonadal development, vimentin appeared in the somatic cells of the thickening surface epithelium, which formed the gonadal ridge. Desmin disappeared and cytokeratins appeared in the Sertoli precursor cells at the inception of their epithelial differentiation. Simultaneously, the prospective Sertoli cells became polarized during their assembly into epithelial cell aggregates; the aggregates then fused and formed elongated testicular cords. The epithelial cell differentiation was accompanied by a deposition of basement membrane material around the cords and by an increase of desmin in the cells immediately around the cords. With further differentiation of the testicular cords, some cytokeratins from the Sertoli cells, but not from the cells of the rete cords, disappeared. On the other hand, other cytokeratin polypeptides and vimentin remained in the fetal Sertoli cells. The surface cell layer slowly differentiated towards a proper epithelium after the basic formation of the testicular cords and interstitium. Desmin and vimentin persisted in the interstitial cells throughout the entire study period. The early differentiation of the gonad is apparently under a general sex-independent initiation program. The developmental changes in intermediate filaments offer an opportunity for the further analysis of their general role in early organogenesis. In light of the genetic theory of testicular differentiation, the functions of the regulatory factor(s) include specific organization of cord cells, histological organization into looping cords rather than separated follicles, and male development of the interstitium, surface epithelium and tunica albuginea. PMID- 1499879 TI - Patterns of immunocytochemically detected Z-DNA in the recrudescing testicular epithelium of the Turkish hamster (Mesocricetus brandti). AB - Z-DNA has been considered a labile but essential structural form of DNA in recombination and gene expression, two significant activities in mammalian seminiferous epithelium. The present study has utilized the recrudescing testes of Mesocricetus brandti to study in detail the potential Z-DNA sites in specific testicular cell types as detected by an immunoprobe. Testicular regression was physiologically induced by modifying environmental photoperiods and/or temperature. Partial atrophy of seminiferous epithelium occurred in all experimental groups but Sertoli cells persisted throughout regression. Recrudescence of testicular activity was marked in all experimental groups by characteristic sequences of reappearance of potential Z-DNA sites to a final positive or negative mature state of the cell type. It is suggested that Z-DNA is a functionally important from of DNA in many cell types of the active seminiferous epithelium of the Turkish hamster, and perhaps other mammals. PMID- 1499880 TI - Characterization of bep1 and bep4 antigens involved in cell interactions during Paracentrotus lividus development. AB - We have identified and partially characterised two antigens, extracted with 3% butanol, from Paracentrotus lividus embryos dissociated at the blastula stage, and encoded by the cDNA clones previously described as bep1 and bep4 (bep-butanol extracted proteins). The cDNA fragments containing the specific central portions of bep1 and bep4 were expressed as MS2 polymerase fusion proteins in Escherichia coli. These two fusion proteins, called 1C1 (bep1) and 4A1 (bep4), were injected subcutaneously into rabbits and the corresponding polyclonal antibodies generated. Western blot analysis of proteins, extracted with 3% butanol, from sea urchin embryos at the blastula stage (b.e.p.), established that both antibodies recognize two 33 KDa proteins. Reducing and non-reducing electrophoretic conditions show that both antibodies against bep1 and bep4 related proteins react also with a protein band of a molecular weight 66 KDa, indicating that these two antigens probably exist as dimers. Immunolocalization with anti 1C1 and 4A1 antibodies shows the presence of the related antigens also on the cell surface. Fab fragments of the polyclonal antibodies against 1C1 and 4A1 inhibited reaggregation of sea urchin embryonic cells, dissociated from blastula stage embryos. This prevention of reaggregation indicates that these proteins probably play a role in cell interaction during sea urchin embryonic development. PMID- 1499881 TI - [Lipid composition of erythrocyte membranes and blood plasma in athletes]. PMID- 1499882 TI - [Effect of aerobic training on the blood supply of the skeletal muscles and structural and metabolic properties of contractile fibers]. PMID- 1499883 TI - [Mechanical energy consumption and efficiency of walking and running]. PMID- 1499884 TI - [Migrating motor complexes in the circadian cycle of activities of daily living]. PMID- 1499885 TI - [Buffer effect of food on food saturation mechanisms in obese patients]. PMID- 1499886 TI - [Thermal sensitivity changes in man during adaptation to cold and hypoxia]. PMID- 1499888 TI - [Advantages of construction of an intracerebral electrode beam in the form of a band]. PMID- 1499889 TI - [Dynamics factor in the functional asymmetry of the cerebral hemispheres]. PMID- 1499887 TI - [Circadian rhythms of parameters of temperature homeostasis in healthy people during acclimatization to arid zone conditions]. PMID- 1499890 TI - [Importance of hemispheric specialization of the temporo-parietal regions of the neocortex in compensatory mechanisms during perceptive activity]. PMID- 1499891 TI - [Electroencephalographic correlates of temporal parameters of simple sensorimotor reactions in people with various levels of functional mobility of nervous processes]. PMID- 1499892 TI - [Automated representation of human visual-motor space tomograms]. PMID- 1499893 TI - [Quantitative electroencephalographic parameters of patients with essential hypertension]. PMID- 1499894 TI - [Intercentral coordination of cortical electric processes during mental activity]. PMID- 1499895 TI - [Perception and evaluation of tactile information in qualified athletes]. PMID- 1499897 TI - [Assessment of minute volume of circulation in patients with myocardial infarction]. PMID- 1499896 TI - [Use of automated systems for evaluation of functional states. IV. Role of parameters of functional asymmetry in the evaluation of psychophysiologic adaptation in administrative personnel]. PMID- 1499898 TI - [Arterial pressure response to orthostasis in arterial hypertension. I. Difference in the arterial pressure response to an orthostatic effect as a function of its initial level in patients with arterial hypertension and in healthy people]. PMID- 1499899 TI - [Effect of passive movements in the talocrural joints on central hemodynamics and heart functional state]. PMID- 1499900 TI - [Change in parameters of the cardiovascular and sympatho-adrenal systems in primary school children during the school year]. PMID- 1499901 TI - [Effect of pharmacologic stimulation of alpha1-adrenoreceptors in the heart and peripheral circulation in elderly and very old people]. PMID- 1499902 TI - Trypsinogen-activation peptides in experimental rat pancreatitis: prognostic implications and histopathologic correlates. AB - Intrapancreatic activation of trypsinogens is believed to occur either as a cause or a consequence of acute pancreatitis and to be associated with the more severe forms of the disease. Trypsinogen-activation peptides (TAPs) were measured in plasma, urine, and ascites of rats (n = 54) assigned to different pancreatitis inducing regimens reproducing the entire spectrum of severity. Compared with survivors, nonsurvivors at 9 hours had significantly higher TAP levels in plasma at 3 hours (P = 0.0001), urine (peak, 1-4 hours) (P = 0.004), and ascites (P = 0.0001) after death. Stepwise discriminant analysis showed that TAP in urine and plasma were the most accurate predictors of outcome (88.2% of animals) compared with other routine laboratory parameters. Morphometric analysis showed that the best histopathologic correlates of TAP elevation were acinar necrosis and intrapancreatic hemorrhage. In a second series of experiments using a homogeneous technique of induction producing pancreatitis with a mortality of 55% at 48 hours, plasma TAP level at 3 hours (cutoff, 0.5 nmol/L) and/or urinary TAP level (peak, 1-6 hours; cutoff, 25 nmol/L) accurately predicted outcome in 85% of animals. It is concluded that the TAP assay gives an accurate early prediction of outcome in different pancreatitis models and correlates best with acinar necrosis and hemorrhage. PMID- 1499903 TI - Possible induction of fatty acid cyclo-oxygenase in lipopolysaccharide-stimulated rat Kupffer cells. AB - In response to stimulation with lipopolysaccharide, isolated rat Kupffer cells released increased amounts of prostaglandin E2, prostaglandin D2, 6-keto prostaglandin F1 alpha, and thromboxane B2. There was a lag of 2-6 hours before a significant release of these metabolites into the medium was detected. Nonstimulated Kupffer cells converted exogenous arachidonic acid to prostaglandins and thromboxane B2, and a major product was prostaglandin D2. Twenty-four hours after stimulation with lipopolysaccharide, Kupffer cells produced approximately 7 times more prostaglandin E2 and 2 times more prostaglandin D2, 6-keto-prostaglandin F1 alpha; and thromboxane B2 than nonstimulated cells. Western immunoblotting of microsomal proteins prepared from the stimulated rat Kupffer cells showed a 70-kilodalton component that was immunoreactive with a polyclonal anticyclo-oxygenase antibody. The intensity of the band increased with the time of the lipopolysaccharide stimulation. These results suggest that the accelerated arachidonate metabolism in lipopolysaccharide-stimulated rat Kupffer cells might be attributed to an induction of the cyclo-oxygenase enzyme. PMID- 1499904 TI - Bile acid transport in the anhepatic rat. AB - Hepatocyte dysfunction eventually results in the loss of canalicular bile formation. Without canalicular flow, intestinal bile acid may originate from plasma by reverse transport. Anhepatic rats with preserved intestinal function permit evaluation of such transport. In the present study, plasma taurocholate clearance was markedly decreased in anhepatic rats. The relative proportion of free cholate increased with time. Peripheral tissues contained virtually only cleared taurocholate, but the intestinal contents were mainly free cholate. This indicates the intestinal contents as the source of the plasma cholate and shows an equilibrium between intestinal and plasma bile acid even without bile flow. The enteral administration of an anion exchange resin to anhepatic rats increased intestinal bile acid recovery and decreased the bile acid recovery in tissue. Plasma bile acid concentration was decreased and fractional loss increased threefold, confirming the anhepatic plasma-intestine bile acid equilibrium. However, the enhanced plasma clearance produced by the resin was less than 1% of the fractional loss found in the intact rat. These data show a very limited bile acid flux between intestine and plasma without bile flow, which could be modestly influenced by an intestinal bile acid sequestrant. PMID- 1499905 TI - Characterization of spontaneous and ethanol-induced gastric damage in cirrhotic rats. AB - Cirrhosis was induced in Sprague-Dawley rats via ligation of the common bile duct. Changes in gastric blood flow and mucosal architecture were examined. Using an ex vivo gastric chamber preparation, the susceptibility of the cirrhotic gastric mucosa to injury by 20% ethanol was also examined. The gastric mucosa of cirrhotic animals was abnormal, even before ethanol administration. The macroscopically visible damage in these animals ranged from superficial hyperemia to epithelial sloughing. These gastric lesions were similar in appearance to the gastropathy described in cirrhotic patients, including "cherry-red spots" and areas of generalized erythema. Cirrhotic rats had a lower resting gastric transmucosal potential difference than control rats, and their gastric mucosa was also significantly more susceptible to damage by topical ethanol application. Ethanol administration caused a significant increase in gastric blood flow in control rats, whereas it significantly decreased gastric blood flow in cirrhotic rats. This lack of a reactive hyperemic response in cirrhotic rats may be responsible for the increased susceptibility of the gastric mucosa to ethanol induced damage. PMID- 1499906 TI - Thiamine transport by basolateral rat liver plasma membrane vesicles. AB - Hepatic thiamine transport is thought to be a saturable, Na(+)- and energy dependent process. However, the transport of this organic cation has not been examined in experimental models that allow direct characterization of carrier mediated processes. Recently, a sinusoidal organic cation/H+ antiport was identified, using N1-methylnicotinamide as a marker. To determine whether thiamine is a substrate for this antiport, the characteristics of thiamine uptake were examined in rat liver basolateral membrane vesicles. An inwardly directed Na+ gradient had no effect on thiamine uptake as compared with an identical K+ gradient. An outwardly directed H+ gradient stimulated thiamine uptake as compared with pH-equilibrated conditions, and H(+)-dependent uptake was not the result of an H+ diffusion potential. Identical pH gradients stimulated uptake under voltage-clamped conditions, consistent with electroneutral thiamine/H+ exchange. Unlabeled intravesicular thiamine trans-stimulated [3H]thiamine uptake. Choline and imipramine cis-inhibited thiamine/H+ exchange; a series of other organic cations and thiamine analogues had no effect. Carrier-mediated [3H]thiamine uptake showed two saturable systems. In conclusion, a thiamine/H+ antiport is present on the sinusoidal membrane, distinct from Na+/H+ and NMN+/H+ exchange. PMID- 1499907 TI - Glycerol interference in serum lipase assay falsely indicates pancreas injury. AB - The measurement of serum lipase activity has been shown to be a very sensitive and specific marker for the diagnosis of pancreatic injury. Two case reports are presented showing that glycerol ingested coincidentally in the formulation of several medications taken therapeutically and given in the emergency room causes a falsely elevated serum lipase activity when measured on the Kodak Ektachem 700 clinical analyzer (Eastman Kodak Co., Rochester, NY). The transient but falsely elevated serum lipase activity could potentially affect the differential diagnosis of patients by the admitting physician. PMID- 1499908 TI - Successful dissolution of cholesterol gallstone during treatment with pravastatin. AB - This case report describes a 51-year-old hypercholesterolemic male patient who had a large solitary cholesterol gallstone. The patient was treated with the 3 hydroxy 3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitor pravastatin, 40 mg/day. After 3 months of therapy, serum cholesterol level normalized (7.7 mmol/L before and 5.2 mmol/L during treatment), and biliary cholesterol saturation index decreased from 1.3 before to 0.8 during treatment. Repeatedly performed ultrasonography showed complete gallstone dissolution. Pravastatin may be valuable in the nonsurgical treatment of cholesterol gallstone disease particularly when there is an additional indication for HMG-CoA reductase inhibitors because of hypercholesterolemia. PMID- 1499909 TI - Immunoproliferative small intestinal disease in an American patient with lymphoma and macroamylasemia. PMID- 1499911 TI - Farther, faster, and (hopefully) better! PMID- 1499910 TI - Gastrointestinal food hypersensitivity: basic mechanisms of pathophysiology. AB - Gastrointestinal symptoms occur in a large number of patients with food allergies. Immediate hypersensitivity mechanisms may give rise to the nausea, vomiting, abdominal pain, and diarrhea experienced by these patients. However, there are limited human data about the pathophysiological basis for these symptoms. Most of the available information comes from a variety of animal models. This article reviews the literature using models of intestinal food hypersensitivity, as well as human studies, that have contributed to our understanding of the pathophysiological mechanisms in gastrointestinal food hypersensitivity. PMID- 1499912 TI - H2-receptor antagonists and blood alcohol levels. PMID- 1499913 TI - Does biliary sludge have the same significance as gallstones in acute pancreatitis? PMID- 1499914 TI - Malabsorption: molecular biology to the bedside. PMID- 1499915 TI - Towards an earlier diagnosis of intestinal infarction? PMID- 1499916 TI - Hepatitis C virus and cryoglobulinemia: unthawing the association. PMID- 1499917 TI - The Sydney system and chronic gastritis. PMID- 1499918 TI - Some German remarks on 'one American response to the Sydney system'. PMID- 1499919 TI - Grading and classification of chronic gastritis: the response of the working party. PMID- 1499920 TI - Histological classification of chronic gastritis: an iconoclastic view. PMID- 1499921 TI - Interleukin-6 production in Crohn's disease. PMID- 1499922 TI - Flow-cytometric assessment of regulatory peptides in Barrett's mucosa. PMID- 1499923 TI - Influence of myenteric neuronal denervation on epithelial cell proliferation. PMID- 1499924 TI - Complementary peptide to the carboxyl-terminal tetrapeptide of gastrin. AB - Codons of noncoding DNA strands for peptides have been found to code for amino acids with hydropathic properties opposite to those of the native peptides. Synthetic peptides, designated as complementary peptides, with amino acid sequences coded by noncoding DNA strands of several peptide hormones have been shown to bind the native peptides. In some instances, antibodies to these complementary peptides have shown agonist or antagonist properties of the native hormones. In this study a peptide was synthesized based on codons complementary to messenger RNA for the carboxyl-terminal gastrin tetrapeptide. This complementary peptide bound radiolabeled human gastrin (G17). Antibodies to the complementary peptide competitively inhibited the binding of 125I-gastrin by canine fundic mucosal membrane preparations. These antibodies also showed gastrin agonist properties in that they stimulated canine gastric mucosal parietal cell [14C]aminopyrine uptake, used as an index of stimulation of gastric acid secretion. Competitive inhibition of 125I-gastrin binding by membrane receptors for gastrin and stimulation of [14C]-aminopyrine uptake by antibodies to the complementary peptide for the gastrin tetrapeptide are consistent with their recognition, binding, and occupancy of gastrin receptors. PMID- 1499925 TI - Enterohepatic circulation is essential for regular cycling of duodenal migrating motor complexes in dogs. AB - The role of enterohepatic circulation and specific bile acids in the initiation and caudad migration of duodenal migrating motor complexes (MMCs) was investigated in conscious dogs. All dogs had spontaneous duodenal MMCs that migrated to the terminal ileum when bile flow was intact. During the first 3 days after total external biliary diversion, no MMCs originated in the duodenum. Instead, all MMCs originated in the jejunum and migrated to the ileum. During the next 4 days of total external biliary diversion, 81% of the MMCs originated in the jejunum and 19% in the duodenum. When normal bile flow was restored after 9 days of total external biliary diversion, regular duodenal MMCs resumed after a delay of 126 +/- 27 minutes. Perfusion of individual bile acids or dogs' own bile, but not saline or alkaline solution, into the duodenum or perfusion of dogs' own bile directly into the ileum during total external biliary diversion restarted duodenal MMCs with a time lag of about 2 hours. The authors conclude that intact enterohepatic circulation is essential for the initiation of regular duodenal MMCs. PMID- 1499926 TI - Helicobacter pylori infection and gastric function in patients with chronic idiopathic dyspepsia. AB - Helicobacter pylori infection, histological features of the gastric mucosa, and gastric motor and secretory functions were evaluated in 45 consecutive patients with chronic idiopathic dyspepsia. H. pylori infection was found in 60% of dyspeptic patients, compared with 33% of 15 healthy controls (P = 0.1). No difference was detected in basal or stimulated gastric acid secretion between dyspeptic patients and healthy controls. Gastric emptying was significantly (P less than 0.01) delayed in dyspeptic patients compared with healthy controls when standardized for age and sex. Delayed gastric emptying was associated with a low frequency of H. pylori infection, female gender, and young age. Epigastric pain or burning and postprandial fullness were, respectively, more severe in patients with H. pylori infection (P less than 0.02) and in those with delayed gastric emptying (P less than 0.01). These findings support the existence of separate subsets of patients with chronic idiopathic dyspepsia. Despite the presence of overlaps, there appear to be partially different functional derangements and clinical features in different subgroups of dyspeptic patients. PMID- 1499927 TI - Effect of acute hyperglycemia on esophageal motility and lower esophageal sphincter pressure in humans. AB - The effect of acute hyperglycemia on esophageal motility and lower esophageal sphincter pressure (LESP) was investigated. Esophageal manometry was performed for 120 minutes in seven healthy volunteers on two separate occasions during euglycemia and during hyperglycemia with blood glucose levels stabilized at 15 mmol/L. At 90 minutes, motility was stimulated with edrophonium chloride (0.08 mg/kg intravenously). Pancreatic polypeptide (PP) secretion was determined as an indirect measure of vagal-cholinergic tone. During hyperglycemia the LESP decreased significantly (P less than 0.05) from 20.1 +/- 1.6 mm Hg to 10.7 +/- 0.6 mm Hg; plasma PP levels were also significantly (P less than 0.05) decreased during hyperglycemia. Edrophonium induced significant (P less than 0.05) increases in LESP and PP levels in both experiments. However, LESP and PP levels after edrophonium stimulation remained significantly (P less than 0.05) reduced during hyperglycemia compared with euglycemia. During hyperglycemia a significant (P less than 0.05) increase in peristaltic wave duration and a decrease in peristaltic velocity were observed in the distal part of the esophagus. It is concluded that blood glucose levels affect esophageal motility, acute hyperglycemia reduces LESP and impairs esophageal motility under both basal and edrophonium-stimulated conditions, and hyperglycemia reduces plasma PP levels, suggesting impaired vagal-cholinergic activity during hyperglycemia. PMID- 1499928 TI - Proliferation assay of human gastric remnant by bromodeoxyuridine and flow cytometry. AB - The cell kinetics of gastric epithelium were studied by bromodeoxyuridine (BrdU) and flow cytometry in seven patients with remnant stomachs reconstructed with a Billroth type II procedure and in 25 patients with whole stomachs. Each patient received an intravenous injection of BrdU (200 mg/m2) 6 hours before surgery. Fresh specimens obtained from the lesser curvature, greater curvature, and stomal areas in the cases of remnant stomachs and from the antrum and fundus in the case of whole stomachs were studied. The BrdU labeling index was higher in the stomal area of the gastric remnant than in other areas, and DNA synthesis time was shortened in the stomal area of the gastric remnant (P less than 0.01) but not in other areas. The turnover time of the mucosa in the stomal area was 4.1 +/- 1.2 days, significantly shorter (P less than 0.01) than in other areas (7.6 +/- 2.3 to 8.2 +/- 1.2 days). The present study showed that the cell proliferation was extremely rapid in the stomal area of the gastric remnant, suggesting that this enhanced turnover of epithelial cells may assist in promoting carcinogenesis in the stomal area of the gastric remnant. PMID- 1499929 TI - Ileocolonic transit does not change after right hemicolectomy. AB - The role of the human ileocolonic junction in the transit of solid contents through the entire gut was evaluated. Eight patients, well compensated after right hemicolectomy for localized colon cancer, and eight age-matched healthy controls were enrolled. Scintigraphic transit was quantified after subjects ingested a mixed meal containing 111In-labeled Amberlite beads (average diameter, 1 mm; Sigma Chemical Co., St. Louis, MO). Gastric emptying was initially faster in the postoperative group, but overall emptying was not different from controls; small bowel transit also did not differ between the groups. In patients in whom the distal ileum, ileocolonic sphincter, and proximal colon were absent, isotopes moved from small to large bowel in a manner that was qualitatively and quantitatively no different from that of controls. Major episodes of coloileal reflux could not be identified in either group. After hemicolectomy, the residual transverse colon, and to a lesser degree the descending colon, were able to store solid residue, although in lesser amounts than the unoperated large bowel. The ileocolonic sphincter in humans appears to play only a minor role, at most, in ileocolonic transit, and the colon remaining after right hemicolectomy stores residue so that bowel habits are not greatly disturbed. PMID- 1499930 TI - Inhibition of rat methylbenzylnitrosamine metabolism by dietary zinc and zinc in vitro. AB - Methylbenzylnitrosamine is an esophageal-specific carcinogen in the rat, and the incidence of methylbenzylnitrosamine-induced esophageal carcinoma is increased by dietary zinc deficiency. Methylbenzylnitrosamine requires activation by cytochrome P-450 to be mutagenic; the present study examined the role of dietary zinc deficiency and the in vitro addition of zinc on the cytochrome P-450 dependent microsomal metabolism of methylbenzylnitrosamine. Dietary zinc deficiency significantly increased the cytochrome P-450-dependent esophageal and hepatic microsomal metabolism of methylbenzylnitrosamine. These changes occurred without alteration in the specific content of total microsomal cytochrome P-450 of the esophagus or liver. The addition of zinc in vitro, at concentrations found in normal tissues, irreversibly inhibited the esophageal and hepatic cytochrome P 450-dependent microsomal metabolism of methylbenzylnitrosamine. These results suggest that physiological levels of zinc may be an endogenous inhibitor of methylbenzylnitrosamine metabolism. Dietary zinc deficiency appears to reduce this inhibition of cytochrome P-450 activity, resulting in an increase in carcinogen activation. PMID- 1499931 TI - Helicobacter pylori in Hispanics: comparison with blacks and whites of similar age and socioeconomic class. AB - Helicobacter pylori infection is twice as frequent in blacks as in whites. It has been postulated that the apparent increase in susceptibility to H. pylori infection in blacks might have a genetic basis. A case-control seroepidemiologic study of H. pylori prevalence was performed in 108 healthy Hispanic volunteers. Eighty-nine Hispanics were matched (1:1:1) with blacks and whites for age and socioeconomic status. There was an inverse correlation between H. pylori infection and educational level that remained after logistic regression analysis adjusting for age and sex. The adjusted prevalence of H. pylori infection was almost identical in Hispanics and blacks and significantly higher than in whites. Because Hispanics do not constitute a race, the increased prevalence of H. pylori in Hispanics and blacks is unlikely to be genetic. It is speculated that the unrecognized bias is a reflection of a generation cohort phenomenon related to the generational distance from very low socioeconomic status, i.e., the prevalence of H. pylori in Hispanics and blacks is currently lower than that of their parents but higher than that of the white population, which has experienced higher socioeconomic status for several generations. PMID- 1499932 TI - The distribution of spinal and vagal sensory neurons that innervate the esophagus of the cat. AB - The distribution of spinal and vagal neurons that convey sensory information from the distal smooth muscle esophagus is poorly documented. Therefore, sensory cell bodies were retrogradely labeled by injecting fast blue into the striated and smooth muscle of the esophageal body and into the lower esophageal sphincter of the cat. The maximum distribution of spinal sensory neuron labeling was found in the following dorsal root ganglia: C1-T8 (striated muscle); C5-L2 (smooth muscle), and T1-L3 (lower esophageal sphincter). Vagal sensory neurons in the nodose ganglion were found to have a crude topographic layout. The total number of vagal sensory neurons labeled by injection into the three esophageal areas was greater than the number of spinal neurons labeled (809.7 +/- 166.1 vs. 328.9 +/- 53.4; mean +/- SEM; n = 12; P less than 0.005). It is concluded that spinal sensory neurons of the esophagus are segmentally arranged. Accordingly, each level of the esophagus has a distinct but overlapping sensory projection to the spinal cord, and afferents from all parts of the esophagus overlap the known spinal distribution of cardiac afferents. PMID- 1499933 TI - Oropharyngeal swallowing in normal adults of different ages. AB - In an effort to evaluate the effect of normal aging on oropharyngeal events of swallowing, 80 normal volunteers, stratified by gender into four age groups, were studied. Liquid and semisolid swallows were performed and recorded simultaneously using videofluoroscopy and manometry. Several parameters, including total duration of oropharyngeal swallowing, were significantly longer in the oldest age group than in any other age group. A delay in initiation of maximal hyolaryngeal excursion primarily accounted for the longer durations with increased age. Significant durational changes also were found as a function of bolus consistency and presence or absence of the manometry tube. Females had a longer duration of upper esophageal sphincter (UES) opening. The amplitude of pharyngeal pressures, duration of peak pharyngeal pressures, and rate of propagation of the contractions were not significantly different for age, gender, or consistency of bolus. No significant differences were found between age groups or between genders in UES pressure. Normal aging affects some parameters of swallowing, while others are preserved. PMID- 1499935 TI - Gastric acidity and gastroesophageal reflux patterns in patients with esophagitis. AB - Esophageal pH-metry is the test of choice for diagnosing gastroesophageal reflux. However, although it allows acid refluxes to be distinguished, it is of limited value for identifying alkaline or mixed (acid mixed with alkaline material) refluxes. To evaluate the ability of dual pH-metry to identify alkaline or mixed refluxes, the gastric acidity and gastroesophageal reflux pattern were evaluated simultaneously in 64 patients with mild-moderate esophagitis, in 28 patients with severe or complicated esophagitis, and in 20 healthy subjects. A dual esophageal gastric pH-probe allowed three different types of esophageal reflux to be distinguished: (a) acid refluxes, defined as a drop in esophageal pH to values less than 4 together with a gastric pH less than 4; (b) mixed refluxes, defined as a drop in esophageal pH from baseline to values greater than 4 associated with rises in gastric pH to greater than 4 values; (c) alkaline refluxes, defined as a rise in esophageal pH to greater than 7 associated with a simultaneous increase in gastric pH to greater than 4. Gastric acidity was more significantly reduced in patients with severe or complicated esophagitis than it was in healthy subjects (P less than 0.01). The reflux pattern in both mild-moderate and severe esophagitis was characterized by mainly acid refluxes and a marked increase in the time the esophagus mucosa was exposed to acid (P less than 0.001). Pure alkaline refluxes were rare (less than 1%) in both healthy subjects and esophagitis patients. The number of mixed refluxes was considerably higher in severe esophagitis patients than it was in either mild-moderate esophagitis patients or controls (P less than 0.05). The finding of mixed refluxes in severe or complicated esophagitis suggests that biliary acids and/or pancreatic enzymes are involved in the pathogenesis of severe forms of esophagitis. PMID- 1499934 TI - Selection of the chimpanzee over the baboon as a model for Helicobacter pylori infection. AB - Baboons (Papio sp.) and chimpanzees (Pan troglodytes) were screened for the presence of Helicobacter pylori. The gastric mucosae of the baboons were colonized by large spiral bacteria. However, a group of adult chimpanzees were identified that were free of spiral gastric bacteria, with five animals being recruited into an H. pylori challenge study. These animals were inoculated orogastrically with one of four strains of H. pylori and followed for up to 26 weeks. H. pylori was established in one of these animals during a primary challenge and in two other animals on secondary challenge. It was shown that the chimpanzee can be infected with H. pylori and that the inflammatory response in these animals mimics that seen in humans. Infection was marked by an antibody response to H. pylori-specific antigens in two animals. It was observed that H. pylori antibody-negative chimpanzees had no apparent infection by H. pylori or related bacteria. Thus serological screening of chimpanzees can be used to identify candidate animals for further evaluation. PMID- 1499936 TI - Objective evidence of aspirin use in both ulcer and nonulcer upper and lower gastrointestinal bleeding. AB - To obtain the best evidence for nonsteroidal anti-inflammatory drug (NSAID) use in gastrointestinal (GI) bleeding, a detailed patient history was supplemented with objective tests of aspirin use, i.e., high-performance liquid chromatography of plasma and platelet cyclo-oxygenase inhibition, which detect aspirin intake within 24 and 120 hours, respectively. Seventy-one patients consecutively admitted for upper or lower GI bleeding and 138 age- and sex-matched controls were studied. Five bleeders were excluded for confounding factors, e.g., warfarin. Of the other 66 bleeders, 45 had upper GI bleeding (28 from peptic ulcer, 14 from duodenal ulcer, and 14 from gastric ulcer) and 21 lower GI bleeding. Evidence of current NSAID use (of which 89% was aspirin) was found in 80% of bleeders vs. 24.3% of controls (P less than 0.0001), for an odds ratio of 13.7 (95% confidence interval, 6.39-27.27). The cyclo-oxygenase test uncovered 21.5% more aspirin users than history alone. Severity of bleeding was not different in acetylsalicylic acid users. The surprisingly high association of current intake of NSAIDs, especially aspirin, with nonulcer GI bleeding including colonic bleeding, changes the conventional view of the following hierarchy of the risk: NSAID----peptic ulcer----bleeding to: NSAIDs----GI bleeding. This view has important implications for current ulcer cotherapy prophylactic strategies, which could fail to prevent greater than 50% of GI bleeding episodes. PMID- 1499937 TI - The muscarinic receptor gene expressed in rabbit parietal cells is the m3 subtype. AB - To investigate the nature of the muscarinic receptors present on parietal cell membranes, binding studies and polymerase chain reaction (PCR) amplification of parietal cell messenger (m) RNA were undertaken. Displacement of N [3H]methylscopolamine by various muscarinic antagonists showed displacement with a single affinity. The apparent dissociation constant values were as follows: atropine (nonselective), 1.95 +/- 0.28 nmol/L; pirenzepine (M1), 169 +/- 24 nmol/L; AF-DX 116 (M2), 1542 +/- 33 nmol/L; and hexahydrosiladifenidol (M3), 29 +/- 3.4 nmol/L. These data confirmed the existence of only an M3 receptor linked to acid secretion as defined pharmacologically. PCR amplification of parietal cell mRNA with primers designed for detection of all known muscarinic receptor subtypes showed that only m3 fragments were produced from parietal cell mRNA, whereas m1 and m2 products could be detected in brain or cardiac mRNA. The m3 nature of the PCR product was confirmed by Southern blotting with 32P-labeled human m3 complementary DNA. Hence the two carbachol affinities and the separable cellular responses following muscarinic activation are caused by separate coupling pathways of the M3 receptor. PMID- 1499938 TI - A wave of inhibition precedes primary peristaltic contractions in the human esophagus. AB - Animal studies have shown that primary esophageal peristalsis is preceded by a wave of inhibition spreading rapidly down the esophagus and lasting longer in more distal segments. In humans, its presence in the esophageal body cannot be demonstrated manometrically because of the absence of tone. To study deglutitive inhibition in humans, an artificial high-pressure zone was created by inflating an intraesophageal balloon to a critical level. The pressure changes at the interface between the balloon and the esophageal wall at various levels along the esophagus were measured. In this artificial high-pressure zone, deglutition induced a relaxation beginning simultaneously at various levels of the esophagus but lasting progressively longer in progressively more distal segments. Latency from onset of deglutition to onset of relaxation at 13 cm and 8 cm above the lower esophageal sphincter and at the lower esophageal sphincter was 0.06 +/- 0.19 seconds, 0.10 +/- 0.31 seconds, and 0.89 +/- 0.53 seconds, respectively; latency to contraction was 4.45 +/- 0.54 seconds, 6.04 +/- 0.79 seconds, and 9.14 +/- 1.04 seconds, respectively. This is the first direct evidence that deglutition produces in the human esophagus a wave of inhibition that precedes the primary peristaltic contraction. PMID- 1499939 TI - p53 gene mutations in gastric and esophageal cancers. AB - The presence of point mutation of the p53 gene in exons 5, 6, 7, and 8 was examined in 10 cases of gastric adenocarcinoma and 5 cases of esophageal squamous cell carcinoma by polymerase chain reaction and direct nucleotide sequencing. Mutations of the p53 gene were found in 5 cases of gastric cancer and 4 cases of esophageal cancer. The mutations in the stomach cancers consisted of four missence mutations (exons 5 and 8) and one frame shift (exon 7). In the esophageal cancers, three missence mutations (exons 6, 7, and 8) and one point mutation within the splice donor site of intron 5 were found. Of the seven missence mutations in the two cancers, five showed the transition from G to A and two from G to T. All these changes occurred in the highly conserved region of the p53 protein. These results suggest that mutations of the p53 gene are genetic events in the pathogenesis of gastric adenocarcinoma and esophageal squamous cell carcinoma. PMID- 1499940 TI - Hyperplasia of histamine-depleted enterochromaffinlike cells in rat stomach using omeprazole and alpha-fluoromethylhistidine. AB - In the rat, gastric histamine is stored mainly in the enterochromaffinlike cells. Gastrin releases histamine from these cells, and long-term hypergastrinemia results in hyperplasia. The effect of sustained hypergastrinemia on histamine depleted enterochromaffinlike cells was studied by measuring histidine decarboxylase activity and histamine concentrations and by using quantitative histology. Hypergastrinemia maintained for 6 weeks was induced by inhibition of gastric acid secretion with omeprazole (400 mumol.kg-1.day-1) given orally, and histamine synthesis was inhibited for the same length of time with alpha fluoromethylhistidine (3 mg.kg-1.h-1) given via osmotic minipumps. In rats given omeprazole alone, the effects of the resulting hypergastrinemia on the enterochromaffinlike cells was reflected in increased histidine decarboxylase activity, increased histamine concentration, and increased number of enterochromaffinlike cells. The general trophic effects on the stomach were seen as increased stomach and oxyntic mucosal weight and increased mucosal thickness. Treatment with alpha-fluoromethylhistidine plus omeprazole markedly reduced the histidine decarboxylase activity and histamine concentration, but the weight of the stomach and oxyntic mucosa, the enterochromaffinlike cell density, and intensity of histidine decarboxylase immunostaining were increased to at least the same extent as after omeprazole alone. These observations indicate that enterochromaffinlike cell histamine is not important for a full expression of gastrin-evoked trophic effects in the stomach. PMID- 1499941 TI - Acute-phase induction of manganese superoxide dismutase in intestinal epithelial cell lines. AB - Cellular protection from immune-generated oxygen free radicals is initiated by the reduction of oxygen radicals by manganese superoxide dismutase (MnSOD) and copper/zinc superoxide dismutase (Cu/ZnSOD). Using rat adult (IEC-6) and fetal (IRD-98) intestinal epithelial cell lines, factors involved in the regulation of the SODs at the messenger RNA (mRNA) level were examined. Exposure of IEC-6 and IRD-98 to Escherichia coli lipopolysaccharide (LPS) or tumor necrosis factor alpha (TNF-alpha) results in a marked increase in MnSOD mRNA as early as at 1 hour. Cotreatment of cells exposed to LPS or TNF-alpha with actinomycin D or cycloheximide showed that de novo transcription but not protein synthesis is required for the LPS- and TNF-alpha-dependent induction in MnSOD mRNA. Treatment with interleukin 1 beta results in a 12-fold increase in MnSOD mRNA, but no change was observed with interleukin 6 or interferon alpha. No change was observed in the level of Cu/ZnSOD mRNA under any condition tested. The results indicate that MnSOD functions as a cytokine-regulated acute phase protein involved in cellular protection from free radical-mediated damage. PMID- 1499942 TI - Effect of intravenous and oral omeprazole on 24-hour intragastric acidity in duodenal ulcer patients. AB - Nine patients with duodenal ulcer were on separate occasions given omeprazole, 20 mg orally, 10 mg intravenously (IV), and 40 mg IV once daily for 5 days. On day 1, the median reduction of 24-hour intragastric acidity was 42.2% for the 20-mg oral dose and 54.8% and 88.4% for the two IV doses, respectively, but the between patient variability was considerable for all three doses. On day 5, the degree of reduction had increased for all three doses to a median value of 99.9% for the 20 mg oral dose and 95.7% and 99.9% for the two IV doses, respectively. Plasma omeprazole concentrations increased significantly from day 1 to day 5 only for the 20-mg oral and 40-mg IV doses. Thus, the increased pharmacological effect of omeprazole during repeated once daily administration can only partly be explained by increased plasma concentrations, suggesting that some additional factor(s) must influence the degree of reduction of 24-hour intragastric acidity. Thus, when determining the optimal dose of omeprazole for acid inhibition, the route and duration of administration must be taken into consideration; after 5 days of once-daily administration of doses as low as 10 mg IV and 20 mg orally are effective and dependable in reducing 24-hour intragastric acidity in patients with duodenal ulcer. However, a daily dose of 40 mg IV omeprazole is not sufficient to keep intragastric pH above 4 in all patients during the first day of treatment. PMID- 1499943 TI - Rectal mucosal pathology varies with human immunodeficiency virus antigen content and disease stage. AB - Rectal mucosal biopsy specimens from 75 human immunodeficiency virus (HIV) seropositive and 16 HIV-seronegative subjects were examined. The histopathologic changes were correlated with immunoperoxidase staining for UCHL-1 and HIV core protein p24, quantitative p24 enzyme-linked immunosorbent assay (ELISA) assay in homogenized rectal tissue and serum, and a modified Walter Reed clinical stage. Four phases were seen in the HIV-infected subjects: (1) early phase, in Walter Reed stage 1-2 subjects, with nearly normal histology and low p24; (2) inflammatory phase, typically in Walter Reed stage 3-4 subjects, with a superficial lamina propria infiltrate of lymphocytes, plasma cells, and eosinophils with degranulation, abundant UCHL-1 staining, and maximal p24 by both immunoperoxidase staining and ELISA; (3) transitional phase, in many Walter Reed 5 and some Walter Reed 6 subjects, with normal lymphocyte population density but with subtle inflammatory changes; and (4) lymphoid depletion phase, mainly in Walter Reed stage 6 subjects, with decreased lymphocytes but often with endothelial cell activation and apoptosis. These phases presumably result from effective HIV suppression by a relatively intact immune system, followed by maximal HIV infection and lymphocyte activation, then progressive lymphocyte depletion. The inflammation correlated with the presence and amount of HIV in rectal tissue determined by immunohistochemistry and ELISA and was maximal before overt immunodeficiency developed. Intestinal mucosa could be a preferred site of HIV proliferation and T-cell destruction. PMID- 1499944 TI - Identification of an abnormal esophageal clearance response to intraluminal distention in patients with esophagitis. AB - Esophageal clearance responses were studied by a new technique comprising a miniature electronic strain gauge attached to an inflatable balloon in 30 normal volunteers and 48 patients with gastroesophageal reflux disease. The pressure changes around the balloon and traction forces acting on the balloon were measured during graded balloon distention (0-12 mL of air for 30 seconds each inflation) in the lower and midesophagus. All normal volunteers responded to distention with development of swallow independent contractions above the balloon [65 mm Hg/30 s (range, 45-100 mm Hg/30 s)] together with generation of an aboral traction force [15 g (range, 9-20 g)]. Patients with reflux esophagitis showed a higher distention threshold for initiation of these responses, induced fewer proximal contractions [24 mm Hg/30 s (range, 0-38 mm Hg/30 s); P less than 0.01 vs. normal], and generated weaker traction forces [4 g (range, 0-6 g) at 10 mL P less than 0.01 vs. normal]. Patients with the most severe esophagitis showed greatest impairment of the clearance response (correlation = 0.7, P less than 0.01) and the greatest esophageal residence of refluxed acid (correlation = 0.5, P less than 0.01). These abnormalities appear to be of relevance to the pathophysiology of esophageal reflux disease although it remains to be determined whether they are the cause, or the result, of the esophagitis. PMID- 1499945 TI - Survival and causes of death in patients with inflammatory bowel disease: a population-based study. AB - Relative survival up to December 31, 1986 was analyzed for all patients diagnosed with ulcerative colitis (UC) (n = 2,509) and Crohn's disease (CD) (n = 1,469) within the Uppsala Region, Sweden 1965-1983. After 10 years survival was 96% of that expected for UC and CD. Patients with ulcerative proctitis, left-sided colitis, and pancolitis at diagnosis had relative survival rates of 98%, 96%, and 93% respectively. Survival did not differ by extent at diagnosis for patients with CD. After including prevalent cases, 684 deaths occurred compared with 481.1 expected deaths [standardized mortality ratio (SMR) = 1.4; 95% confidence interval (CI) = 1.3-1.5]. Inflammatory bowel disease was the main reason for this excess mortality. Colorectal cancer increased mortality (50 deaths observed vs. 15.2 expected). Death from other cancers were not greater than expected. Obstructive respiratory diseases, especially bronchitis, emphysema, and asthma increased mortality SMR = 1.5 (95% CI = 1.1-2.2) in UC. Cerebrovascular disease mortality occurred less often than expected (SMR = 0.7; 95% CI = 0.5-1.0). Mortality for other diseases and groups of diseases was close to that expected. PMID- 1499946 TI - Inhibition of pancreatic adenocarcinoma cell growth by lovastatin. AB - RAS protein (p21 ras) requires farnesyl (an intermediate of cholesterol synthesis) for activation. Activating mutations of K-ras gene have been detected in most human pancreatic adenocarcinomas. In the present study, the effect of lovastatin, an inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A, the rate limiting enzyme of cholesterol synthesis, on the growth of five pancreatic cancer cell lines (human-CAV, MIA Paca2, CAPAN2 and PANC1, and hamster-H2T) in vitro and of two cell lines (CAV and H2T) in vivo was examined. Inhibition of cell growth was observed with lovastatin doses at or above 2.5 micrograms/mL for H2T, CAV, MIA Paca2, and CAPAN2 or 10 micrograms/mL in PANC1. The H2T cell line was studied further to determine the reversibility of growth inhibition. Mevalonic acid (1 mmol/L) reversed lovastatin-induced inhibition of cell growth if it was added with lovastatin (2.5 micrograms/mL). Similarly, removal of lovastatin from the medium within 24 hours after treatment allowed recovery of cell growth. The effect of lovastatin on cell growth was irreversible after 48 hours of exposure. The survival fraction of H2T cells was markedly decreased by 1- or 24-hour exposure to 75 micrograms/mL but not to doses ranging from 0.5 to 60 micrograms/mL of lovastatin. Growth of pancreatic carcinoma xenografts (CAV and H2T) in nude mice was inhibited by a subcutaneous infusion of lovastatin (50 micrograms/h). These results indicate that mevalonic acid or a metabolite in the cholesterol synthesis pathway is necessary for growth of pancreatic cancer cells and suggest that lovastatin should be further examined as a potential therapeutic agent for pancreatic cancer. PMID- 1499947 TI - Adrenergic modulation of interdigestive pancreatic secretion in humans. AB - Whether the adrenergic pathways participate in the control of interdigestive pancreatic function in humans is uncertain. To determine if changes in alpha- or beta-adrenergic tone modulate interdigestive pancreatic enzyme output, 16 healthy subjects were intubated with an orojejunal tube to collect and quantify pancreatic trypsin secretion and record motility. After observation of a complete interdigestive cycle (control period), eight groups of two subjects each received 2-hour intravenous infusions of the alpha- and beta-agonist epinephrine (50 ng.kg 1.min-1), the alpha-antagonist phentolamine (5 mg/2 min followed by 500 micrograms/min), the beta-antagonist propranolol (5 mg/2 min followed by 80 micrograms/min), or saline as control, alone or in combination. Drugs were assigned in a random mode according to a 2(3) factorial design. Analysis of variance showed that epinephrine decreased trypsin output by 43% (P less than 0.05). By contrast, trypsin output was increased fourfold in the presence of phentolamine (P less than 0.01), whereas propranolol had no effect. These data suggest that an inhibitory alpha-adrenergic tone modulates human interdigestive pancreatic enzyme secretion whereas beta inputs are less important. PMID- 1499948 TI - Early midzonal oxidative stress preceding cell death in hypoperfused rat liver. AB - Intralobular heterogeneity of oxidative stress and its topographic relationship with cell death during low-flow hypoxia were shown in perfused rat liver by digital microfluorography using dichlorofluorescin diacetate, a fluorochrome sensitive to intracellular hydroperoxide formation, and propidium iodide, which labels the nuclei of nonviable cells. The surface of the liver loaded with two precursors was microscopically visualized, and the fluorescence of dichlorofluorescein, a highly fluorescent molecule generated by hydroperoxide mediated dichlorofluorescin oxidation, was digitally processed. Dichlorofluorescein fluorescence significantly increased in midzonal regions as early as 20 minutes after starting the 25% low-flow hypoxia. At 40 minutes the fluorograph showed multiple dotted patterns, and the intensity peaked at 60 minutes. The onset of cell death studied by propidium iodide was observed at 40 minutes, and its topographic distribution corresponded to the dichlorofluorescein enhanced midzonal regions. Allopurinol diminished the early midzonal oxidative stress and retarded the onset of cell death. The current findings show that xanthine oxidase-dependent oxidative stress and the resultant cell death during low-flow hypoxia are spatially restricted in the intermediate zone between the periportal and pericentral regions. PMID- 1499949 TI - [Environmental pollutants and fertility disorders. Heavy metals and minerals]. AB - So far, the influence of lead, cadmium and mercury on human fertility has hardly been considered. First experiences by the authors with the chelating agent 2,3 dimercaptopropane-1-sulfonate (DMPS), which mobilizes heavy metals deposited in the body, seem to favour an association between the body load of heavy metals and complications during the menstrual cycle and during pregnancy. By means of an extensive survey of references, the importance of heavy metals for reproduction is demonstrated. In addition, the deficiency of particular minerals and their interaction with heavy metals are considered. Indications are given for diagnosis and therapy of the exposure to heavy metals. The practical procedure is demonstrated by means of three case studies. PMID- 1499950 TI - [Ultrasound diagnosis of blood flow in benign and malignant breast tumors]. AB - Malignant tumours can be differentiated from the benign ones by their vascular blood supply. We employed three methods to analyse the blood flow: the angiodynograph, the duplex system, and the continuous-wave Doppler method, and measured the blood flow in 151 patients on the preoperative day. Histology revealed a malignoma in 92 cases and a benign tumour in 59 cases. It was found, that in more than 90% of the malignomas, a high blood flow was identified in or around the tumour by means of the colour method (angiodynography), which could be quantified by the pulsed-wave Doppler. A significantly lower blood flow was evident in the benign tumours with a markedly increased resistance index (by 80%) established by means of the pulsed-wave Doppler. Continuous-wave (CW) Doppler showed a significantly higher blood flow with almost all malignomas in the entire breast, than was the case with benign changes. Our studies showed, that the enhanced blood flow in and around malignant tumours can be visualised by means of update technology, angiodynography being particularly suitable for demonstrating the flow by the B-mode. Quantification, however, is, at present, only possible by employing the duplex method with pulsed-wave Doppler. CW Doppler is suitable only for blood flow diagnosis of the entire organ, but it requires great precision of working method and is time consuming; tumour blood flow cannot be visualised on target by this method. PMID- 1499951 TI - [The diagnostic value of rectal ultrasound in the assessment of parametrial infiltration of cervix cancer]. AB - In addition to rectal palpation, rectosonography seems to be a promising method in pretherapeutic examination of the parametrium in patients with cervical carcinoma. To evaluate the usefulness of this examination we determined the sensitivity and specificity of rectal palpation performed by one examinator, rectal palpation performed by changing examiners, and rectal sonography. The results of the clinical examination of 128 parametria (64 women) were compared to histological findings following Wertheim-Meigs operation. Sensitivity and specificity were as follows one examiner 48% and 96%, changing examiners 44% and 94%, rectosonography 55% and 99%. In conclusion, we suggest that rectal sonography is a careful and moderate method that can be an important supplement to rectal palpation in pretherapeutic staging of cervical cancer. PMID- 1499952 TI - [On the value of "informational evening classes for mothers and fathers" within the scope of prenatal care]. AB - In 1989, the Department of Gynaecology and Obstetrics, University of Cologne, questioned the 288 participants of the "informative evenings for mothers and fathers", a primarily preventive measure offered as a preparation for childbirth. The survey aimed at reviewing these evenings, i.e. to make a critical and exact evaluation of their usefulness and quality as one of the numerous events offered to expectant mothers. The following results were obtained: The women who visited the informative evenings were mostly pregnant for the first time, educated above average, for the most part working women and of German nationality. Their attitude towards preventive measures, i.e. regular check-ups during pregnancy as well as smoking behaviour, the wish to breast-feed and the attendance of other birth preparation courses, is well founded. Consequently, this group of women can be described as a highly selected. Their motivation to come to the evenings resulted mostly from the wish to obtain specific clinical information, to become familiar with the maternity ward, to meet midwives and doctors, in order to lose some of their fears and to increase confidence. Contents and structure of these evenings were mostly able to meet the expectations of the visitors. Unsatisfactory, however, was the low number of foreign woman, those with difficult pregnancies and women of a low social status i.e. patients, who above all, need intensive assistance and attention. PMID- 1499953 TI - [Differential diagnosis of seizures in the peripartal period]. AB - Seizures remain an important cause of maternal morbidity and mortality during pregnancy and the puerperium. Encouraged by some cases treated in our clinic (9 cases have been observed between 29. 12. 1989 and 22.5. 1991), the management of differential diagnosis in seizures are discussed in this article. Despite all possibilities of using technical apparatus for investigations, case history and clinical examination remain the basics of diagnosis with regard to paroxysm. EEG is an important, noninvasive method for judgement of cerebral function. It can be carried out continuously as a bedside-test and is extremely helpful in the differential diagnosis of eclampsia versus epilepsia. With a view to substantial defects as a possible convulsant factor, visualised examination procedures, e.g. cranial computed tomography (CCT) and magnetic resonance imaging (MRI) are available. Especially MRI has advantages in the diagnostic procedure. It could help to find the cause of cerebral structure defects and to clear the question of aetiology. Thus, a specific therapeutic procedure might become possible. PMID- 1499954 TI - [Drug dependence, smoking and fetal growth retardation]. AB - Illicit drug abuse, as well as smoking, are known risk factors in the development of intrauterine growth retardation. In an attempt to clarify the influence of these two aetiological factors, a retrospective analysis was carried out. 35 drug and nicotine-addicted pregnant women were compared to 104 smokers and 101 non smoking controls with regard to foetal outcome. Relative risk estimates for intrauterine growth retardation of the drug and nicotine group were 3.14 (95% confidence limits 1.88-5.25; p = 0.0001) whereas the smoking group had 1.39 (95% confidence limits 0.96-2.02; p = 0.0482) compared to non-smoking controls. The foetal outcome was best in the latter group: children of drug-addicted mothers had a considerably higher morbidity and mortality rate. This study shows an almost threefold risk for intrauterine growth retardation in drug-addicts who smoke, compared to nicotine abuse alone. PMID- 1499955 TI - [Fibromatosis of the breast]. AB - Fibromatosis of the breast is a rare benign mesenchymal transformation of the connective tissue, the origin of which is probably situated in the fascia of the pectoral muscle and the Cooper's ligaments. In the clinical and radiological examination, it is difficult to differentiate between a mammary carcinoma or other malignant tumours of the breast. Only histological examination can lead to the final diagnosis. Large-scale excision of these tumours, which have a tendency to relapse, is the therapy of choice. The diagnostic problems are shown in a case of a 26-year old patient. PMID- 1499956 TI - [Ovarian cancer in ovarian remnant syndrome?]. AB - We report on a malignant pelvic tumour in a 69-year old woman, whose uterus and adnexa had been removed 22 years ago because of endometriosis. Clinical and pathological findings pointed to an ovarian cancer in an ovarian remnant syndrome. In a case of a carcinoma, it is difficult to furnish proof of an ovarian remnant syndrome. Differential diagnoses, especially the ureteral adenocarcinoma, are discussed. PMID- 1499957 TI - [Obstetrical management of dysfibrinogenemia with increased thrombophilia]. AB - Dysfibrinogenaemias are characterised by qualitatively abnormal fibrinogen, causing functional defects. In pregnant women, the incidence of recurrent abortions and placental abruption as well as haemostatic complications is high. In this case report, we report on a 22 year old woman with dysfibrinogenaemia complicated by thrombotic episodes. After two stillbirths under dramatic circumstances (placental abruption, eclampsia) and after an early abortion (7th gestational week), the patient was treated by subcutaneously administered heparin. Pregnancy ended successfully by delivery in the 39th gestational week. PMID- 1499958 TI - [Response to a letter to the editors by Prof. M. Mall, PD Dr. I. Werner-Zodrof and PD Dr. P. Huber (Geburtsh. u. Frauenheilk. 51 (1991) 1014]. PMID- 1499959 TI - Chronic lingual ulceration. PMID- 1499960 TI - Recurring palatal ulceration. PMID- 1499961 TI - Considerations for selecting effective analgesic regimens in dental practice. AB - A variety of analgesic regimens can be developed, based on sound pharmacological principles, in response to the empirical estimate of pain intensity. Including optimal doses of nonopioids to reduce the amount of opioid required is recommended. Furthermore, when pain is anticipated, the nonopioid regimen can be administered on a regular schedule rather than as needed. Preventing pain is better than attempting to reduce it after full intensity has been reached. Careful selection of an effective regimen can prevent breakthrough pain, along with stress and anxiety, which are factors that often require desperate attempts for relief. Options for the dentist to consider are summarized in Table 5 and may be simulated through substitution of other NSAID or opioid equivalents. PMID- 1499962 TI - A review of the guided tissue regeneration concept. PMID- 1499963 TI - Stabilized baseplates: a technique. PMID- 1499964 TI - Skin tumors may imitate infectious processes. AB - A small nodule on the middle finger of the right hand of a right-handed dentist was removed and found to be benign. The lesion recurred and showed increased collagen deposition and vascularity; it was diagnosed as a dermatofibroma. In the absence of a specific incidence of trauma, the cause of such a lesion is a matter of speculation. Such lesions can develop as local tissue reactions to wounds that are the result of routine operatory procedures. This points to the need for careful handling of sharp instruments. Because of the serious consequences of a malignancy or infection from HIV, nodules and other lesions of unknown etiology that appear suddenly should not be ignored. PMID- 1499965 TI - Adverse reaction to dental corticosteroids. AB - The case of an 18-year-old woman who experienced prominent, episodic cognitive dysfunction and affective symptoms, which coincided with a brief administration of dexamethasone, has been presented. Because her symptoms were subtle and intermittent, and because she was no longer taking corticosteroids when she sought medical attention, the diagnosis of a corticosteroid-induced mental disorder was delayed. This case demonstrates the need for heightened awareness, among all practitioners, of the effects of corticosteroids on mental functions. Because it is not possible to predict who will experience mental disturbances with even small doses of corticosteroids, all patients (and their families, if possible) should be informed about the possibility of adverse reactions. Dentists and physicians need to weigh the risks and benefits of corticosteroid therapy carefully. Clinicians also should be suspicious of psychiatric disturbances in proximity to corticosteroid use (i.e., even in a patient who is not taking corticosteroids, but who has a history of corticosteroid treatment). PMID- 1499966 TI - A three-rooted mandibular second premolar. AB - If an endodontic problem is diagnosed in a mandibular premolar, and root canal therapy is provided, it must be considered that second and third canals might exist. Although the existence of a third canal would be rare, a thorough evaluation may help to prevent future complications. In the case presented here, failure to recognize a third canal might have resulted in incomplete instrumentation and canal obturation, and endodontic failure. Variations in root canal morphology and the number of canals might not have been detected even during close inspection of the pulp chamber floor. Therefore, the dentist must have a thorough knowledge of root canal morphology and its variations. PMID- 1499967 TI - A personal remembrance of Dr. Louis I. Grossman. PMID- 1499968 TI - Can a patient make an irrational choice? The dental amalgam controversy. PMID- 1499969 TI - Expansile bone lesion. PMID- 1499970 TI - Multiple oral ulcers. PMID- 1499971 TI - PCR pin-anchored anterior fracture restorations. PMID- 1499972 TI - Surgical management of the fractured tooth. PMID- 1499973 TI - Use of a portable X-ray device during Operation Desert Storm. PMID- 1499974 TI - Geriatric pharmacology and dental implications. PMID- 1499975 TI - Amalgam-derived mercury. PMID- 1499976 TI - Subcutaneous emphysema involving a week-old extraction site. PMID- 1499977 TI - Audiotaped relaxation, implosion, and rehearsal for the treatment of patients with dental phobia. PMID- 1499978 TI - Recruitment within the groups of gamma 1, alpha 2 and alpha 3-motoneurons in dogs and humans following bladder and anal catheter pulling. AB - Conduction velocity frequency distribution histograms were constructed from lower sacral root recordings of single intrafusal (gamma) and extrafusal (alpha) motoneurons. The velocity distributions of occasional and stimulated activity before and following bladder and anal catheter pulling were almost identical for dogs and humans. The limits of the velocity ranges of alpha 1(FF), alpha 2(FS) and alpha 3(S) and gamma beta(?)-motoneurons were determined from the broadness of the single peaks. The borders of the partly fused peaks of gamma 1 and gamma 21-motoneurons were estimated from their different functional properties. Activity levels of the alpha 1, alpha 2, alpha 3, gamma beta, gamma 1 and gamma 21-motoneurons were too complex to allow safe conclusions from the dog measurements, probably because of the representation of leg and tail in addition to sphincter functions in the lower sacral root. In the human dorsal S4 root, in which mainly efferent functions of sphincters only were contained, the gamma 21, gamma 1, alpha 2 and alpha 3-motoneurons showed simple behaviour. Distribution changes of conduction velocities in each group of alpha and gamma-motoneurons were used for recruitment analysis. Following stimulation in dogs and humans, within the groups of gamma 1, alpha 3 and alpha 2-motoneurons, slowly conducting fibres were activated before the faster conducting ones. The alpha 3-motoneurons were recruited later than the alpha 2-motoneurons. In the dog, low gamma 1 and alpha 2-motoneuron velocities occurred preferentially 0 to 0.2 s following strong bladder catheter pulling, probably in the mono- and oligosynaptic pathways. Low conduction velocities of alpha 3-motoneurons occurred more often 1 to 1.2 s following stimulation. At 2 to 2.2 s following stimulation, the high gamma 1 and alpha 2-motoneuron velocities were more activated. At 4 to 4.2 s following stimulation, low gamma 1 and alpha 2-motoneuron velocities were recruited again. Following strong bladder catheter pulling, co-recruitment of the gamma 1 and alpha 2-motoneurons seemed to occur. Following anal catheter pulling in the dog there was no co-recruitment of gamma 1 and alpha 2-motoneurons. In the case of gamma 1-alpha 2 co-recruitment, the gamma 1-motoneurons were recruited additionally once in between the co-recruitment. The higher frequency of recruitment of the gamma 1-motoneurons, and the separate recruitment of the gamma 1 and alpha 2-systems, indicate that the activation of gamma 1 and alpha 2 motoneurons are not strongly linked.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1499979 TI - Ventral root afferent and dorsal root efferent fibres in dog and human lower sacral nerve roots. AB - Two pairs of wire electrodes were used to record single afferent action potentials from ventral roots and single efferent action potentials from dorsal roots of dogs and humans. A human lower sacral ventral root contained about 20 to 30% afferents among fibres with a diameter larger than 5 microns; a comparable ventral root of a dog contained about 1% afferents. Human S3, S4 and S5 dorsal roots contained 3, 18, and 20 to 30% efferent fibres respectively; a comparable dorsal root of the dog contained less than 1% efferent fibres. Primary and secondary muscle spindle afferents, Golgi tendon organ afferents, and afferents from the mechanoreceptors of the urinary bladder and anal canal mucosa were activated in a dog ventral root by pulling bladder and anal catheters. Their peak group conduction velocities were 82, 57, 71 and 18 m/s at 34 degrees C respectively. The dog afferents conducted more than 30% faster than did comparable human nerve fibres. By strongly pulling the bladder catheter, the static human dorsal root gamma 21-motoneurons increased their activity for about 7 s which in turn strongly increased the dorsal root spindle afferent activity for more than 10 min; the human static intrafusal gamma-motoneurons seemed to show cumulative properties. PMID- 1499980 TI - Alamethicin-induced pore formation in biological membranes. AB - The effects of alamethicin on the membrane barrier function of rabbit erythrocytes, human platelets and sarcoplasmic reticulum vesicles, as well as on that of brain microsomes and liver mitochondria of the rat were compared. An upset of the barrier function was observed for plasma membranes of brain microsomes as well as for erythrocyte and platelet membranes at alamethicin concentrations ranging between 25-80 micrograms/ml. The membrane barrier functions of sarcoplasmic reticulum vesicles, of endoplasmic reticulum vesicles of rat brain microsomes, and of liver mitochondria were disturbed at 3-7 micrograms/ml alamethicin. The different sensitivities of plasma and intracellular membranes to alamethicin were supposed to be due to the presence of considerable quantities of cholesterol in plasma membranes as well as to peculiarities of their protein compositions. PMID- 1499981 TI - Threshold stimulation and accommodation of the Hodgkin-Huxley axon. AB - The charge-duration and strength-duration relations for just threshold rectangular stimuli were numerically investigated for the Hodgkin-Huxley axons of different lengths and different membrane capacitances under normal conditions and blockage of the development of accommodative processes. Two linear portions could be distinguished on the charge-duration curve. One of them followed the Weiss law. The other one represented a portion of a straight line passing through the zero point of the coordinates. The slope of the second portion was determined by the charge for very short stimuli (Q0), the slope of the first portion, and the maximum time to excitation (tau max). The rheobase reflected the slope of the second portion. Upon varying the fibre length the slope of the first and the second linear portions and the rheobase changed. The membrane capacitance substantially affected both the value of Q0 (as in the case of myelinated fibres) and the rheobase. The accommodative processes affected the Q0, the slope of the first line, tau max, and, consequently, the rheobase. The effect of potassium activation was stronger than that of sodium inactivation. The slope of the first line, tau max, and the rheobase might be considered more comprehensive indicators of the accommodative processes than the usually used indicators. PMID- 1499982 TI - Effect of stimulus (postsynaptic current) shape on fibre excitation. AB - Effects of variation of the stimulus pulse shape on the excitation of a nonmyelinated nerve fibre were studied using a mathematical model based on the Hodgkin-Huxley equations. Efficiency of smoothly changing pulses was compared with that of rectangular pulses. For pulses shorter than the time to excitation, the rate of the stimulus rise did not determine the ability of a smoothly changing pulse to excite the fibre. For a given stimulus duration, the main factor was the pulse area or the charge delivered by the pulse. The strength duration curve for smoothly changing pulses was a nonmonotonic function, in contrast to the curve for rectangular pulses. The dependence of latency on changes in the pulse area was non-linear. It would be nonmonotonic when the pulse area variation were due to the stimulus duration or the stimulus rise duration. More that one propagating intracellular action potential (IAP) could arise upon fibre activation by a long smoothly changing threshold stimulus. Upon activation of relatively short fibres the IAP could arise not at the site of the smoothly changing stimulus injection. The rectangular pulses of long duration were more efficient than the corresponding smoothly changing ones. Irrespective of the shape, the pulses whose duration at the foot is 1-2 ms, are more suitable for a prolonged threshold fibre activation. PMID- 1499983 TI - Group conduction velocities and nerve fibre diameters of alpha and gamma motoneurons from lower sacral nerve roots of the dog and humans. AB - Single action potentials and their conduction times were recorded extracellularly from dog and human lower sacral nerve roots. Conduction velocity frequency distribution histograms were constructed and peaks of single extrafusal and intrafusal motoneuron distributions were identified. The electrophysiologically measured roots were removed and morphometrically analysed. Nerve fibre diameter frequency distribution histograms were constructed with respect to 3 myelin sheath thickness ranges, and peaks of single motoneuron group distributions were identified. The identified motoneuron classes, characterized by their group peak values of conduction velocity at about 36 degrees C and fibre diameter were: dog: intrafusal: gamma 22(23ms-1/4.8 microns),gamma 21(33/5.7), gamma 1 (43/6.7),gamma beta?(54/10.1) extrafusal: alpha 3(61ms-1/11.7 microns),alpha 2(72/13.6), alpha 11 (81/15.2), alpha 12(86/16.8),alpha 13(95/19) human: intrafusal: gamma 21(15ms 1/5.8 microns), gamma 1(20/6.8), gamma beta?(27/7.2) extrafusal: alpha 3(37ms 1/8.3 microns),alpha 2(50/10.2), alpha 1(60/13.1) The 60 (alpha 3) to 30% (alpha 1-motoneurons) higher conduction velocities in dogs as compared to humans seem to originate in the 40 (alpha 3) to 30% (alpha 1-motoneurons) larger nerve fibre diameters. However, the myelin sheath seemed to be 0.1 to 0.2 microns thinner in dogs than in humans. The pair-values "conduction velocity-fibre diameter" of the alpha and gamma-motoneuron groups were lying on different correlation curves in the velocity-diameter plane indicating structural and/or geometrical differences between alpha and gamma-motoneurons. PMID- 1499984 TI - Plasmid maintenance in Bacillus stearothermophilus is strain-dependent. AB - We studied the segregational stability of plasmids based on pTB913, a 4.5-kb rolling-circle plasmid derived from the thermophilic Bacillus plasmid pTB19. In Bacillus stearothermophilus the stability of pTB913 derivatives appeared to be strain-dependent. In strain CU21 large amounts of single-stranded pTB913 DNA were found and the plasmid was highly unstable at 57 degrees C. In strain NUB3621, however, very low amounts of single-stranded plasmid DNA were formed and pTB913 based replicons were only slightly unstable at 57 degrees C. The NUB3621/pTB913 host-vector system seems appropriate for molecular cloning. A RepA-based replicon, also derived from pTB19 but replicating by a theta mechanism, was highly unstable in B. stearothermophilus NUB3621. PMID- 1499986 TI - Electrochemical sterilization of bacteria absorbed on granular activated carbon. AB - The electrochemical sterilization of bacteria adsorbed on granular activated carbon (GAC) was demonstrated. The survival ratio of bacteria on GAC was dependent upon the applied potential. The survival ratio of Escherichia coli, Staphylococcus aureus, Bacillus subtilis and Saccharomyces cerevisiae vs. saturated calomel electrode (SCE) was below 1% at 0.75, 0.8, 1.0 and 0.65 V, respectively. The electrochemical sterilization of tap water containing E. coli was carried out when 3.5 ml of the cell suspension (4.0 x 10(2) cells/ml) was incubated with 2.0 g of GAC for 5 h at 0.7 V vs. SCE. The number of E. coli adsorbed on GAC and the cell concentration in the water decreased rapidly. E. coli on GAC were electrochemically killed and the cell numbers did not increase. PMID- 1499987 TI - Transconjugants of Agrobacterium radiobacter harbouring sym genes of Rhizobium galegae can form an effective symbiosis with Medicago sativa. AB - It is known that the Rhizobium galegae genomes contain megaplasmids. The suicide vector pSUP2111 with nifH gene of R. meliloti was introduced into the strains CIAM 0703 and CIAM 0711 of R. galegae inducing effective nodules on Galega orientalis plants. The formation of self-transmissible megaplasmids was observed. The megaplasmid transfer into non-nodulating R. meliloti mutants resulted in partial complementation of the nodulation defect in recipient strains though only one transconjugant showed the nitrogen-fixing activity in symbiosis with alfalfa and another one in symbiosis with G. orientalis plants. Among the Agrobacterium strains harbouring R. galegae megaplasmids there were four classes of transconjugants: (1) Nod+ Fix- in symbiosis with goat's rue plants (three strains); (2) Nod+ Fix- on Medicago sativa (two strains); (3) Nod+ Fix+ on M. sativa (five strains); (4) Nod- with both plant hosts (11 strains). PMID- 1499988 TI - Description of conidia from submerged cultivation of Thermomyces lanuginosus for use as a uniform inoculum. AB - Conidia produced by submerged cultivation of the thermophilic fungus Thermomyces lanuginosus were superior to conidia from agar plates when used as inoculum, due to a faster and more synchronous germination. With conidia derived from submerged liquid culture at 40-45 degrees C more than 90% germination was achieved at 50 degrees C within 3 h whereas the same percentage germination was only achieved after 5 h incubation of conidia produced on agar plates. The temperature during conidial formation, and conidial age at the time of harvesting, were factors influencing germination of the conidia. PMID- 1499989 TI - Cloning of poly(3-hydroxybutyric acid) synthase genes of Rhodobacter sphaeroides and Rhodospirillum rubrum and heterologous expression in Alcaligenes eutrophus. AB - From genomic libraries of the purple non-sulfur bacteria Rhodospirillum rubrum Ha and Rhodobacter sphaeroides ATCC 17023 in the broad-host range cosmid pVK100, we cloned a 15- and a 14-kbp HindIII restriction fragment, respectively. Each of these fragments restored the ability to accumulate poly(3-hydroxybutyrate) (PHB), in the PHB-negative mutant Alcaligenes eutrophus PHB-4. These hybrid cosmids also complemented PHB-negative mutants derived from wild-type R. rubrum or R. sphaeroides. Both fragments hybridized with the PHB synthase structural gene of A. eutrophus H16 and conferred the ability to express PHB synthase activity. Only the 15-kbp HindIII fragment from R. rubrum conferred on the mutant PHB-4 the ability to form large PHB granules (length up to 3.5 microns). PMID- 1499990 TI - Ageism: rhetoric and reality. PMID- 1499991 TI - Toward second-generation nursing home research. PMID- 1499992 TI - Gerontology and critical theory. PMID- 1499994 TI - In search of a discourse on aging: the elderly on television. AB - This article analyzes the images of aging presented in five of the prime-time television programs of 1989 most watched by the elderly: Murder, She Wrote, The Golden Girls, Matlock, Jake and the Fatman, and In the Heat of the Night, all of which have central elderly characters. An examination of the title sequences reveals that earlier television stereotypes of the elderly "as more comical, stubborn, eccentric, and foolish than other characters" have been replaced by more positive stereotypes of them as powerful, affluent, healthy, active, admired, and sexy. PMID- 1499993 TI - Cohort change in images of older adults, 1974-1981. AB - This study examines images of older people held by adults of all ages at two points in time. The two surveys, 7 years apart (1974 and 1981), permit the examination of cohort changes in such perceptions over time. Multivariate analysis indicated that social class and health status evaluations of older adults declined between the two surveys, principally because of the assessments by more recent cohorts. With regard to media portrayals of older adults, more recent cohorts felt that the media portrayals of older adults were distorted by presenting a more positive picture than what older people actually experienced. PMID- 1499995 TI - Subjective age: a test of five hypotheses. AB - This paper discusses the concept and measurement of subjective age. Five hypotheses are proposed based on earlier studies of subjective age and tested using data from 607 randomly selected adults from five states. The data supported only two of the hypotheses: (1) the agreement between chronological age and subjective age declines steadily throughout the adult decades and (2) people in their 30s are the most likely to see themselves as different, either younger or older, from their chronological age. We conclude that generalizations about subjective age may depend on the subjects providing the data. PMID- 1499996 TI - The quo vadis of gerontology: on the scientific paradigm of gerontology. AB - A critical examination of fundamental assumptions of gerontological research reveals problematic sources of concept and theory development. For example, the misery and resource perspectives on aging and the aged are viewed as "overflow" from ideals of Western society. When empirical findings conflict with researchers' theories, the latter must be reexamined and revised. We should look to the aged themselves for new hypotheses, and focus on such concepts as creativity, wisdom, and play. PMID- 1499997 TI - Improving nursing home care through training and job redesign. AB - Nursing assistants have the primary contact with older residents of nursing homes. The Penn State Nursing Home Intervention Project's short-term longitudinal study assessed the single and combined effects of two interventions designed to affect nursing assistants' performance by increasing their knowledge and motivation: skills training and job redesign. Statistically significant differences in nursing assistants' knowledge were evident in comparisons between intervention and control sites, but performance was not improved. Implications for policy, practice, and research are discussed. PMID- 1499998 TI - Ineffective staff, ineffective supervision, or ineffective administration? Why some nursing homes fail to provide adequate care. AB - This study involved 530 nursing staff working in 25 for-profit and nonprofit nursing homes, two of which failed to meet resident care standards required for state recertification. Staff members' job attitudes, opinions regarding elderly residents, and perceptions of the organization climate varied between the successful for-profit and non-profit homes. The organization climate in the failed homes was significantly different from the climate in either the successful for-profit or successful nonprofit homes. PMID- 1499999 TI - Personal and environmental influences on nursing home satisfaction. AB - Data were collected from the administrator, staff, and a sample of 289 residents in 51 nursing homes in order to assess the influence of organizational factors on residents' satisfaction with the nursing home. Longevity of personnel, level of benefits, wages for nursing assistants and their perception of the charge nurse's fairness and competence as well as the degree of personalization of residents' rooms were all related to residents' satisfaction with the nursing home. PMID- 1500000 TI - The role of support in alleviating stress among nursing assistants. AB - This paper provides a direct test of the buffering hypothesis that the negative effects of stressors (measured as burden, burnout, and perceived job pressure) on nursing assistants working in long-term care institutions are moderated by social support (at work and external to work). The buffering hypothesis was not confirmed, though some support for a main effects view was found. Social support at work, specifically training to work with residents with cognitive impairment, and support from family and friends can assist nursing assistants in dealing with burnout and perceived job pressure. However, major steps in alleviating burden, burnout, and perceived job pressure must be to decrease or change the workload and provide rewards on the job. PMID- 1500001 TI - Nurse's aides in nursing homes: the relationship between organization and quality. AB - This study examines the work of the nurse's aide through a combination of participant observation and in-depth interviews with 30 nurse's aides. Data were analyzed using the grounded theory method of constant comparative dimensional analysis. Findings suggest that strategies developed by individual nurse's aides to organize their work are important determinants of both the quality of care and worker turnover. Quality of care may be better explained by Litwak's theory about the difficult juxtaposition between primary and formal groups than by the nurse's aides' lack of knowledge. PMID- 1500002 TI - Adaptation and age-related expectations of older gay and lesbian adults. AB - Results from a study of lesbian women and gay men in the Midwest over the age of 50, who indicate high levels of involvement in the gay community, provide a picture of the aging process of these adults that builds on previous research efforts. Respondents reported acceptance of the aging process, and high levels of life satisfaction, despite predictable problems associated with aging and sexual orientation. Being active in the gay community was an asset to accepting one's own aging. PMID- 1500003 TI - Black and white dementia caregivers: a comparison of their adaptation, adjustment, and service utilization. AB - We compared black (n = 33) and white (n = 119) caregivers of dementia patients on indices of adaptation, adjustment, and utilization of supportive services. Black and white caregivers differed most notably on marital and financial/insurance status, but there were few differences between them in their adaptation to dementia responsibilities. Black caregivers, however, evidenced less burden and less desire to institutionalize their relatives and were more likely to report more unmet service needs than were whites. PMID- 1500004 TI - An evaluation of a group program for spouses of frail elderly veterans. AB - We examined the effectiveness of a multicomponent group program for spouses of frail aging veterans that included support, education, problem solving, and stress reduction. Compared with caregivers who received no intervention, those in the group program showed significant increases in use of active behavioral coping strategies, knowledge of community resources, perceived independence in the marital relationship, and personal changes in the caregiving relationship. They also experienced significant decreases in subjective burden and the stress and severity of caregiving problems. PMID- 1500005 TI - A longitudinal analysis of factors related to survival in old age. AB - Data from a longitudinal study of the elderly in rural North Wales are used in an exploratory study of the relationships between very broadly defined social circumstances and longevity. A statistical modeling approach is adopted and has some nonroutine features necessitated by missing data on dates of death. A variety of demographic, socioeconomic, social network, quality-of-life, dependence, and health variables are found, individually, to be related to survival. Multivariate analysis demonstrated that many of these relationships are spurious and, in particular, there is no prima facie evidence that survival is affected by social networks or quality-of-life factors. However, socioeconomic factors emerge as important for the old elderly. PMID- 1500006 TI - Nursing home responsiveness to research requests: results of a field study. AB - This study used data from a random sample of Wisconsin nursing homes to analyze nursing homes' response to requests to participate in a field study. Multiple organizational characteristics predicted responsiveness. Facilities with greater financial resources were more likely to grant access to researchers. Stable administration and local facility control predicted higher response rates to a survey of nurses. Stable ownership and stable administration predicted higher resident consent rates. PMID- 1500007 TI - Senior-to-senior mediation service project. AB - Conflicts experienced by elderly persons regarding housing, consumer problems, the quality and availability of health and social services, family problems, and other issues often require mediation. This program demonstrates the important potential of using seniors as volunteer mediators to assist other seniors. It also suggests that training in conflict management skills enhances competence of volunteers in solving their own conflicts. PMID- 1500008 TI - A "school of headache" concept, practical arrangements, and experiences with a systematic education in headache research and clinical practice. PMID- 1500009 TI - Clinical neurophysiology studies in headache: a review of data and pathophysiological hints. AB - In migraine between attacks EMG studies are normal. Recordings during attacks need to be performed. Temporalis exteroceptive silent period is useful in the differential diagnosis of headaches and sheds some light on the pathophysiology of tension-type headache. PMID- 1500010 TI - Time information in Poggendorff visual illusion: visual evoked potentials. AB - Using the component sets of the Poggendorff visual illusion as optical stimuli (comprising two horizontal and parallel segments intersected by two oblique segments), we recorded the respective visual evoked potentials (VEPs). Depending on the different delta t passing between the constitutive elements of the Poggendorff illusion, it was found that there was a greater latency of VEP components for the visual stimulus presentation sequence in which oblique segments are projected before horizontal segments. PMID- 1500012 TI - Urodynamic evaluation of 12 ataxic subjects: neurophysiopathologic considerations. AB - Twelve ataxic subjects (seven with Friedreich's heredo-ataxia and five with a cerebellar vascular or traumatic lesion) were examined by way of urodynamic evaluation. The results explain the role the cerebellum plays in the modulation of the micturition reflex and confirm the importance of bilateral encephalic damage in causing vesico-sphincteral malfunctioning and the important role of the lateral myelon cords in transporting bladder proprioceptive sensitivity. PMID- 1500011 TI - Epilepsy associated with hypocalcemia: description of a family. AB - The unusual occurrence of epilepsy and hypocalcemia in the same family is described. Epilepsy was present in three siblings (convulsive generalized in two females and partial in one male). All six family members had calcium ion, plasmatic phosphorus, plasmatic and erythrocytic potassium, urine calcium and phosphate concentration below the normal levels. Altered values of calcium induced potassium membrane permeability were found in three subjects (two of them also affected by epilepsy). The assumption that alterations of membrane structure or function play an essential role in determining familial epilepsy and that the normal "set point" for calcium is genetically determined in familial hypocalcemia could explain the concomitance of both pathologies to some extent. PMID- 1500013 TI - The significance of positive peritoneal cytology in endometrial cancer. PMID- 1500014 TI - Positive peritoneal cytology is an adverse factor in endometrial carcinoma only if there is other evidence of extrauterine disease. AB - The prognostic significance of peritoneal cytology among 269 women with clinical stage I and II carcinoma of the endometrium was studied. All patients were surgically staged and had undergone selective pelvic and para-aortic lymphadenectomies. Patients with clear cell and papillary serous carcinomas were excluded from the analysis. Thirty-four (12.6%) patients had malignant cells in the peritoneal washings (positive peritoneal cytology). The effect of positive peritoneal cytology on survival depended upon the extent of disease present. If the disease was confined to the uterus, positive peritoneal cytology did not influence survival; if the disease had spread to the adnexa, lymph nodes, or peritoneum, positive peritoneal cytology had a significant adverse effect on survival, decreasing it at 5 years from 73 to 13%, all recurrences being at distant sites. These findings suggest that treatment specifically directed at positive peritoneal cytology is not warranted unless extrauterine disease is present, and when it is, systemic rather than intra-abdominal treatment will be required to affect survival. PMID- 1500015 TI - A matched comparison of single and triple incision techniques for the surgical treatment of carcinoma of the vulva. AB - Thirty-two patients with invasive squamous cell carcinoma of the vulva (SCC) undergoing radical vulvectomy or radical local excision with bilateral superficial groin node dissection using a triple incision technique (TI) were matched for new FIGO stage, lymph node status, size of lesion, and site of lesion with patients with SCC undergoing traditional radical vulvectomy with en bloc bilateral groin (but not pelvic) node dissection using a single incision (SI) technique. Average operative time (134 min: 191 min), blood loss (424 ml: 733 ml), and hospital stay (9.7 days: 17.2 days) were significantly less in the TI group. After SI 6/32 (19%) patients and after TI 1/32 (3%) patients experienced complete breakdown of the groin wounds. There was no significant difference in overall survival (P = 0.56) or disease-free survival (P = 0.53) between the two groups. There was no significant difference in survival between the two groups by lesion size or by FIGO (1989) stage. Disease recurred in six patients after SI compared with seven after TI (P = 0.75). There were no skin bridge recurrences in the TI group. Two patients in each group had isolated vulvar recurrences and all four were successfully treated by local excision. These data indicate that outcome following TI surgery is essentially equal to that of SI in early-stage disease but major morbidity is much reduced. PMID- 1500016 TI - Total and lipid-bound serum sialic acid as markers for carcinoma of the uterine cervix. AB - Concentrations of total sialic acid (TSA) and lipid-bound sialic acid (LSA) were determined in serum samples from 88 patients with squamous cell carcinoma of the cervix, 26 normal subjects, and 44 patients with benign uterine or ovarian disease. TSA concentrations in patients with cervical cancer were found to correlate with advanced-stage disease. LSA concentrations were only increased in stage IV of the disease. Sensitivity of the test for stage IB was zero for TSA and 27% for LSA. The specificity of both markers was about 80% due to a low incidence of false-positive values in the pathologic control group. Measurements of TSA or LSA appear to be of no value for the early detection of cervical cancer or to complement the clinical staging of this tumor. PMID- 1500017 TI - Trafficking of syngeneic murine lymphokine activated killer T cells following intraperitoneal administration in normal and tumor bearing mice. AB - Nongenetically restricted T cells may be important host effector cells in women with ovarian cancer receiving intraperitoneal (ip) IL-2 therapy. We developed an in vitro technique to produce murine lymphokine-activated killer T cells. Murine splenocytes were cultured in the presence of 1000 U/ml IL-2 for 10 to 15 days. Phenotypical analysis showed 95% of total cells to express the pan T phenotype Thy 1.2 and no NK cell phenotypes by Day 7 in culture. These cells were labeled with 51Cr and their trafficking pattern after ip administration into normal and M5067 tumor bearing mice was examined. Various organs and tissues were collected at different timepoints and monitored for radioactivity. Within 4 hr., about 60% of the counts were associated with the bowel, peritoneum, and omentum of both normal and tumor bearing mice. About 15% of counts were associated with the blood, lung, kidney, spleen, and liver of both normal and tumor bearing mice. PMID- 1500018 TI - A clinicopathological study of 30 melanomas of the vulva. AB - Thirty cases of malignant melanomas of the vulva were studied for prognostic factors. Ulceration, tumor thickness, and positive inguinal lymph nodes were the most important prognostic factors. Morphometry did not demonstrate any prognostic meaning. Traditionally a radical vulvectomy and bilateral inguinal lymph node dissection were the therapy of choice, but this treatment modality did not show a better survival than less radical treatment. A low-risk and a high-risk group of patients have been identified for recurrence. The low-risk patient has a nonulcerative tumor, less than 3 mm thick, without clinical evidence of inguinal lymph node metastases, and should be treated by local excision with a 2- to 3-cm margin. The high-risk patient has a tumor which is ulcerative and/or more than 3 mm thick and should also be treated by local excision without elective inguinal node dissection. If clinical suspicion of inguinal lymph node metastases exists, an inguinal node dissection is advocated for better local control of the disease. PMID- 1500019 TI - A randomized trial of adjuvant chemotherapy after radical hysterectomy in stage Ib-IIa cervical cancer patients with pelvic lymph node metastases. AB - Seventy-one patients with Stage Ib-IIa cervical cancer treated by radical hysterectomy and found to have pelvic lymph node metastases were entered on a randomized trial comparing standard pelvic radiotherapy versus three cycles of combination chemotherapy with cisplatin, vinblastine, and bleomycin followed by pelvic radiotherapy. After a median follow-up of 2.5 years, 24 patients have relapsed. In 12 patients, the first evidence of relapse was in the pelvis, in 11 patients the first relapse was evident at a distant site, and in 1 patient the local recurrence and distant metastases were documented simultaneously. No difference in disease-free or overall survival has emerged between the two treatment groups. Relapse was more common in patients with non-squamous tumors (44%) and in those with metastases in several pelvic lymph nodes. We conclude that patients with pelvic lymph node metastases have a rather poor prognosis, but it remains to be determined how they should best be treated after radical surgery. PMID- 1500020 TI - The significance of cone biopsy resection margins. AB - This 12-year retrospective study examines the significance of margin involvement with dysplasia at cone biopsy in relation to follow-up. Of 300 cone biopsies, 123 (41%) had margin involvement. These cases of margin involvement were associated with more severe dysplasia (P less than 0.0001) and a higher chance of subsequent abnormal cytological follow-up (P less than 0.0001) and residual dysplasia at subsequent surgery (P less than 0.0001). Involvement of the endocervical margin at the initial cone biopsy was a sensitive predictor of future abnormality, with an incidence of subsequent abnormal cytology of 29% and residual disease of 82% in those undergoing further surgery. In those cases where the margins had been clear, the incidence of abnormal cytological follow-up was 8%, with 12% residual disease in those undergoing subsequent surgery. Margin involvement was a better predictor of residual disease at repeat surgery than abnormal follow-up cytology (positive predictive value, 79% vs 60%, respectively). PMID- 1500021 TI - Endoluminal ultrasound staging of cervical cancer. AB - Clinical staging of cervical cancer is incorrect in approximately one-third of patients who undergo surgical staging. Pretreatment laparotomy is the staging method of choice for patients with cervical cancer at Memorial Sloan-Kettering Cancer Center. We performed transabdominal, transvaginal, and transrectal ultrasound staging on 12 patients. In 5 of 6 patients undergoing radical hysterectomy, clinical ultrasound and surgical staging were consistent. One patient could not tolerate rectal probe sonography. Ultrasound staging was correct in 1 of 6 patients with advanced disease. A new technique of cervical imaging with transrectal ultrasound and vaginal douche is described. We believe it unlikely that ultrasound will improve the accuracy of clinical staging in patients with cervical cancer. PMID- 1500022 TI - Long-term follow-up of ovarian cancer with monthly determinations of serum CA 125. AB - Monthly serum CA 125 determinations were used for monitoring of 33 patients with advanced nonmucinous epithelial ovarian cancer during the follow-up after the primary treatment. The observation time ranged between 3 and 7 years. All patients had elevated CA 125 levels at the start of chemotherapy with subsequent normalization during treatment. Seventeen patients were classified as having no evidence of disease during the whole follow-up period. Out of 649 samples analyzed from these patients only 6 of the samples from 4 patients were greater than 35 U/ml (rate of false positives, 0.9%). These high values were all singular; the serum samples for the preceding and following months were normal. Out of 20 verified recurrences in 15 patients, 19 had elevated CA 125 levels (sensitivity, 95.0%). The CA 125 increase was the only sign that initiated clinical investigation in 16 recurrences (sensitivity for early diagnosis, 80.0%). With examination under anesthesia, fine needle aspiration for cytology, CT scan, and sometimes laparoscopy or laparotomy a relapse could be verified in 13 of these cases (sensitivity for the whole procedure, 65.0%). In 2 recurrences the increase in CA 125 was obvious at the same time as the clinical evidence of recurrence and in 1 case the elevation was delayed. One additional patient is presently under investigation because of an increase in CA 125. We conclude that monitoring with monthly determinations of serum CA 125 is a reliable method with very few false-positive values. We regard this as a step forward in the management of the follow-up of ovarian cancer patients. PMID- 1500023 TI - Carcinoma of the cervical stump. AB - Treatment, prognosis, and complication rate were retrospectively studied in 46 patients with cervical stump cancer. There were no differences in clinical stage distribution and histopathological findings between these patients and patients with cervical cancer of the intact uterus. However, 43 patients were treated by radiation therapy and only 3 patients had a cervical amputation. The 5-year survival rate was 62%, which is comparable to that of cervical cancers. Late complications were found in 22 patients: 3 (7%) had symptoms of severe radiation reactions of the bladder (necrosis or vesicovaginal fistels), 14 (31%) had severe radiation reactions in the rectum and the sigmoid (severe proctitis, stenosis, or rectovaginal fistels) and 7 (18%) had large vault necrosis. It is concluded that the frequency of cervical stump cancer is low, but cancer in the cervical stump is difficult to treat and the rate of severe late complications is so high that it should be considered when one is deciding between supravaginal and total hysterectomy. Moreover, screening for cervical cancer should be performed regularly after supravaginal hysterectomy. PMID- 1500024 TI - Descriptive epidemiology of ovarian cancer in Europe. AB - Trends in ovarian cancer mortality over the period 1955-1989 were analyzed for 25 European countries (excluding the Soviet Union and a few small countries) on the basis of the official death certification data from the World Health Organization database. The overall variation in age-standardized ovarian cancer mortality at all ages declined appreciably, from over 17-fold during the period 1955-1959 (i.e., between 10.5/100,000 in Denmark and 0.6/100,000 in Spain, world standard) to 3.4-fold (i.e., between 9.9/100,000 in Denmark and 2.9/100,000 in Spain) in the late 1980s. When a comparison was made between the late 1950s and the 1980s, ovarian cancer mortality increased in most European countries, except Denmark, Sweden, and Switzerland, where certified mortality was already elevated in the late 1950s, although also in these countries the peak rate around or over 10/100,000 was reached during the 1960s. However, when the changes over the last decade were considered, ovarian cancer mortality trends were downward in all Nordic countries, Germany, Switzerland, Austria, and Czechoslovakia. Mortality was rising somewhat, though to a smaller extent, in Ireland, Britain, and Southern Europe. Trends were more favorable in middle-aged women (35 to 64 years), and, to an even greater extent, in young women (aged 20 to 44), among whom substantial declines, particularly over the last decade, were observed in most European countries, approaching 50% in Britain and Scandinavia. These trends are discussed in terms of changes in risk factor exposure (i.e., trends in average parity and oral contraceptive use), diagnostic and therapeutic improvements, ovariectomy, and changes in case ascertainment and certification. PMID- 1500025 TI - Intraperitoneal cisplatin chemotherapy in ovarian carcinoma patients who are clinically in complete remission. AB - Three courses of intraperitoneal cisplatin chemotherapy with systemic thiosulfate protection were administered to 31 stage II-IV ovarian carcinoma patients who were clinically in complete remission after completion of postoperative cisplatin based combination chemotherapy. The 5-year survival rate was 60.4% and the median progression-free interval 35 months. Among 25 patients who underwent second-look laparotomy, the survival and the duration of the progression-free interval were significantly better in those with a pathologically confirmed complete response. Short-term intraperitoneal cisplatin chemotherapy should be considered for consolidation of treatment in ovarian carcinoma patients who are clinically in complete remission. PMID- 1500026 TI - Preoperative serum CA-125 levels in borderline tumors of the ovary. AB - Preoperative serum CA-125 levels were evaluated in 38 patients who underwent primary surgery for epithelial ovarian tumors of borderline malignancy at the Brigham and Women's Hospital and Massachusetts General Hospital between 1981 and 1990. Surgical staging was Stage I in 25 (66%) patients, Stage II in 2 (5%) patients, Stage III in 10 (26%) patients, and Stage IV in 1 (3%) patient. The mean sizes of mucinous and serous ovarian tumors were 21.9 and 10.3 cm, respectively (P = 0.0002). All 13 patients (100%) with mucinous tumors had Stage I disease, while 12 (50%) of 24 patients with serous tumors were Stage I. Combining all cell types, 10 (40%) of 25 patients with Stage I disease had an elevated preoperative CA-125 level, while 2 (100%) of 2, 9 (90%) of 10, and 1 (100%) of 1 patient with Stage II, III, and IV disease, respectively, had increased preoperative levels. Among patients with serous tumors, 3 (25%) of 12 Stage I patients had an elevated preoperative CA-125 level, while 11 (92%) of 12 Stage II-IV tumors had elevated levels (P less than 0.001). These data suggest that preoperative CA-125 level correlates with stage of disease in patients with serous borderline ovarian tumors. PMID- 1500027 TI - Phase II trial of amonafide in previously treated patients with advanced ovarian cancer: a Southwest Oncology Group study. AB - Twenty-three patients with metastatic or recurrent Stage III or IV epithelial ovarian cancer who were refractory to or relapsed following previous chemotherapy with cisplatin or a cisplatin analog were entered into a phase II study of amonafide. The starting dose of amonafide was 300 mg/m2 delivered daily over 1 hr by intravenous infusion. In the absence of myelosuppression, the dose of amonafide was escalated by increments of 75 mg/m2 to a maximum of 450 mg/m2. There were 19 eligible and 17 fully evaluable patients. Grade 3 or 4 leukopenia occurred in 14 (74%) patients and grade 3 or 4 thrombocytopenia in 6 (32%) patients. No objective complete or partial responses were observed. Four patients had stable disease for 3, 4, 4.5, and 6 months, respectively. Therefore, amonafide in the doses used in the present trial does not have significant activity in previously treated patients with ovarian cancer. PMID- 1500028 TI - Successful treatment of persistent partial mole with oral methotrexate therapy. AB - Two patients with persistent partial molar pregnancy were successfully treated with oral methotrexate therapy. The advantages of this form of therapy are discussed. PMID- 1500029 TI - Bronchial metastases from ovarian carcinoma. Report of a case and review of the literature. AB - A patient with ovarian cystadenocarcinoma developed respiratory insufficiency due to bilateral endobronchial metastases, 6.5 years after treatment of the primary tumor. Ovarian cancers frequently metastasize to the pleura and lung parenchyma. Clinically significant bronchial metastases are rare. Only three cases have been reported previously. As in our patient, bronchial metastases tend to occur after a relatively long interval from diagnosis of the primary tumor, and survival may be prolonged after their appearance. PMID- 1500030 TI - Choriocarcinoma in a term placenta with maternal metastases. AB - Choriocarcinoma of the nonmolar placenta is presumptively a rare entity and is usually associated with widespread maternal metastases at the time of diagnosis. Nonmetastatic disease goes unrecognized and undiagnosed because placental carcinoma can be limited to a few villi, and grossly evident disease is often misinterpreted as a placental infarct. The optimal treatment for patients with choriocarcinoma of the placenta is not known but aggressive combination chemotherapy is suggested for patients with metastatic disease. Historically, the prognosis for both mother and infant has been poor. PMID- 1500031 TI - Choroidal metastasis from primary ovarian carcinoma. PMID- 1500032 TI - Inhibition by butylated hydroxytoluene and its oxidative metabolites of DMBA induced mammary tumorigenesis and of mammary DMBA-DNA adduct formation in vivo in the female rat. AB - The phenolic food antioxidant butylated hydroxytoluene (BHT) has been reported to inhibit the initiation stage of 7,12-dimethylbenz[a]anthracene (DMBA)-induced mammary tumorigenesis in the female rat. However, the mechanism for this antitumorigenic effect of BHT is unknown. The present studies were conducted to evaluate the relative effect of the parent chemical BHT and two of its major oxidative metabolites, 2,6-di-tert-butyl-4-hydroxymethylphenol (BHT-BzOH) and 2,6 di-tert-butyl-1,4-benzoquinone (BHT-quinone), on DMBA-induced rat mammary tumorigenesis and on the formation of rat mammary DMBA-DNA adducts in vivo. The ip administration of either BHT or BHT-quinone at 200 mg/kg body weight for 2 wk before until 1 wk after DMBA administration inhibited the development of mammary tumours as compared with controls. The extent of tumour inhibition by BHT (39%) was greater than that exhibited by BHT-quinone (25%). The administration of BHT BzOH at 200 mg/kg body weight did not inhibit mammary tumorigenesis. Thus, the inhibition of DMBA-induced mammary tumorigenesis by BHT does not appear to be mediated by the oxidative BHT metabolites BHT-BzOH or BHT-quinone. In addition, there was a good quantitative correlation between the inhibition of mammary tumorigenesis by BHT and BHT-quinone and their respective abilities to decrease total binding in vivo of DMBA to mammary DNA. The inhibition of specific mammary DMBA-DNA adducts by BHT was not identical to the inhibition of adducts by BHT quinone. However, the decrease in formation of the major mammary adduct derived from the anti-dihydrodiolepoxide of DMBA bound to deoxy-guanosine most closely correlated to the relative abilities of BHT and BHT-quinone to inhibit mammary tumorigenesis. When mammary adduct formation was examined in response to BHT dose, the administration of BHT at doses of 100 mg/kg body weight and 200 mg/kg body weight resulted in the inhibition of anti-derived but not syn-derived mammary DMBA-DNA adducts. Together, these studies suggest that in addition to the inhibition of total mammary DMBA-DNA adduct formation, the inhibition of mammary DNA adducts formed from the anti-dihydrodiolepoxide of DMBA also may be specifically important in the inhibitory effect of BHT on DMBA-induced mammary tumorigenesis. PMID- 1500033 TI - Influence of modulators of epoxide metabolism on the cytotoxicity of trans anethole in freshly isolated rat hepatocytes. AB - The effect of modulating epoxide metabolism by inhibiting microsomal and cytosolic epoxide hydrolases and depleting glutathione, on the cytotoxicity of trans-anethole has been examined in freshly isolated rat hepatocytes in suspension. Hepatocytes derived from female Sprague-Dawley CD rats by collagenase perfusion were incubated in suspension and sampled at intervals over a 6-hr period. Cytotoxicity was assessed by the leakage of lactate dehydrogenase into the culture medium and in the cells after lysis. Glutathione was determined by fluorimetry. Anethole showed a dose-dependent cytotoxicity at concentrations ranging from 5 x 10(-4) to 5 x 10(-3) M, with concentrations of 10(-3) M and above causing greater than 63% leakage of lactate dehydrogenase in 6 hr. Microsomal epoxide hydrolase was inhibited by trichloropropene oxide (10(-4) M) and cyclohexene oxide (10(-3) M), and cytosolic epoxide hydrolase by 4 fluorochalcone oxide (5 x 10(-4) M). Cellular glutathione was depleted by diethyl maleate (5 x 10(-4) M), and its synthesis inhibited by 2.5 x 10(-3) M-L buthionine (S,R)-sulphoximine. Suspensions treated with a sub-cytotoxic concentration of anethole (5 x 10(-4) M) showed a rapid increase in cytotoxicity when 4-fluorochalcone oxide was present (complete loss of viability within 2 hr), while pretreatment of hepatocytes with diethyl maleate in combination with buthionine sulphoximine, to deplete glutathione, slowly increased the cytotoxic response at later times (after 4 hr of incubation). The association of the effects of 4-fluorochalcone oxide with the inhibition of cytosolic epoxide hydrolase is strengthened by the inability of chalcone oxide, a close structural analogue of 4-fluorochalcone oxide, which has no effect on epoxide hydrolase or glutathione conjugation, to influence the effects of anethole on hepatocytes. These data are discussed in terms of the role of anethole epoxide in the cytotoxicity of trans-anethole. PMID- 1500034 TI - Optimization of the sensitivity of high-performance liquid chromatography in the detection of heterocyclic aromatic amine mutagens. AB - Solid-phase extraction with the weak cation-exchange resin Fractogel TSK CM650(S) (TSK CM) was used to optimize the sensitivity and chromatographic resolution by HPLC of the mutagenic heterocyclic aromatic amines MeIQx, 4,8-DiMeIQx, IQ, MeIQ, PhIP, Trp-P-1, Trp-P-2, amino-alpha-carboline and the co-mutagens norharman and harman. The clean-up using cation exchange was applied after purification on Extrelut and propylsulphonic acid-silica gel cartridges (PRS tandem purification). Only the clean-up with TSK CM enabled low detection limits of the mutagenic compounds to be achieved (in the order of ng heterocyclic amines/g experimentally overheated process-flavour sample). PMID- 1500035 TI - Vomitoxin-induced dysregulation of serum IgA, IgM and IgG reactive with gut bacterial and self antigens. AB - The effect of dietary vomitoxin exposure on immunoglobulins that react with naturally occurring gut bacterial and self antigens was assessed in the B6C3F1 mouse. Ingestion of 25 ppm vomitoxin for 4 and 8 wk resulted in significantly elevated total IgA but depressed total IgG and IgM in serum when compared with control mice fed semi-purified diet only. IgA specific for phosphorylcholine (PC) and inulin (haptens associated with intestinal bacteria) increased significantly in mice fed vomitoxin whereas IgM with the identical specificity decreased. When sera were assessed for autoantibodies recognizing DNA and bromelated mouse red blood cells (MRBC), vomitoxin-exposed mice exhibited elevated specific IgA as compared with controls. This occurred together with decreases in DNA-specific IgG and IgM, and decreases in MRBC-specific IgM. Additionally, vomitoxin exposure did not enhance the specific serum IgA response to orally administered trinitrophenylated sheep red blood cells (TNP-SRBC), but significantly depressed TNP-specific serum IgG. The results suggest that hyperelevation of total and specific serum IgA for oral and self antigens occurs during vomitoxin feeding and that may be coupled with down-regulation of total and specific IgM or IgG. These effects could be contributory to the capacity of vomitoxin to induce IgA immune complex glomerulonephritis. PMID- 1500036 TI - Genetic toxicology of acrylic acid. AB - Acrylic acid was tested for gene mutations in the in vitro CHO/HGPRT assay, for chromosome aberrations in CHO cells in culture, and for potential to induce unscheduled DNA synthesis in rat hepatocytes in culture. In vivo assays performed included the Drosophila sex-linked recessive lethal assay by both the feeding and injection routes, the in vivo cytogenetic assay in rat bone marrow cells after both a 1-day and 5-day oral dosing regimen, and a dominant lethal assay in mice by both an acute and 5-day dosing regimen. All results were negative (non mutagenic) except for the in vitro chromosome aberration assay. This latter result is consistent with the previously reported possible clastogenic activity suggested by the results of the mouse lymphoma L5178Y TK locus assay in which a predominance of small-colony mutants was observed (Moore et al., Environmental and Molecular Mutagenesis 1988, 11, 49-63). The rapid clearance of acrylic acid in animals and the weight of evidence of genetic toxicity testing, including negative in vivo data in both somatic and germ cells, indicate a lack of genetic toxicity of acrylic acid in vivo. PMID- 1500037 TI - Comparative study of the biodisposition of benzanthrone in different rodent species. AB - The bio-elimination and organ retention of [14C]benzanthrone, an anthraquinone dye intermediate, were determined in rats, mice and guinea pigs. Urinary excretion of benzanthrone during 96 hr was higher in guinea pigs (28%) compared with rats and mice (19%). However, faecal elimination during 96 hr was higher in rats (39%) and mice (42%) than in guinea pigs (25%). Urinary elimination of benzanthrone in rats and mice was highest between 12 and 24 hr, while guinea pigs showed a peak value between 24 and 48 hr. The maximum amount of radiolabelled benzanthrone was eliminated through faeces at 24-48 hr in all the three animal species. The retention of [14C]benzanthrone in the liver was comparable in rats (11.2%) and mice (11.9%), while in guinea pigs it was substantially higher (21.9%). The testes of rats and mice were devoid of radioactivity, whereas those of guinea pigs showed a marginal retention (1.25%) of 14C. The present study suggests that guinea pigs are more prone to benzanthrone toxicity than are rats and mice since the bio-elimination of this compound is slower and its organ retention is higher in this species. PMID- 1500038 TI - Inhibition by germanium oxide of the mutagenicity of cadmium chloride in various genotoxicity assays. AB - The effects of germanium oxide on the genotoxicity of cadmium chloride were investigated. The incorporation of [3H]thymidine into testicular DNA was inhibited in mice injected ip with 1.35, 1.80 or 2.70 mg cadmium chloride/kg body weight. Germanium oxide (0.05 or 0.1 mg/kg body weight, sc) alone did not affect [3H]thymidine incorporation into testicular DNA but 0.05 mg germanium oxide/kg antagonized the inhibitory effect of 1.35 mg cadmium chloride/kg. However, combinations of the other doses of the two compounds did not show statistically significant antagonistic effects. Cadmium chloride significantly increased the frequencies of micronucleus formation in polychromatic erythrocytes, and of chromosome aberrations in the bone marrow of mice treated with 0.7, 1.4 or 2.7 mg/kg body weight, in a dose-related manner. These effects were inhibited by germanium oxide at doses of 0.1 or 0.5 mg/kg body weight, although germanium oxide alone did not affect micronucleus formation or the chromosome aberration rate. Cadmium chloride produced a dose-related increase in the frequency of sister chromatid exchanges in cultured human lymphocytes at concentrations of 5, 10 or 50 mumol. This effect was also inhibited by germanium oxide (0.05 or 0.1 mumol), although germanium oxide alone had no effect. There was a dose-related increase in the frequency of sperms with abnormal head morphologies from mice treated with 0.6, 1.1 or 2.2 mg cadmium chloride/kg body weight and this too was antagonized by the injection of germanium oxide (0.1 or 0.5 mg/kg body weight). Germanium oxide alone did not affect the frequency of sperm-head abnormalities. PMID- 1500039 TI - An update on research with coffee/caffeine (1989-1990). AB - The interest in research with coffee has been increasing in recent years, and this has resulted in a surge of publications dealing with a variety of pharmaco physiological effects of coffee/caffeine. This review attempts to update the information on the research with coffee/caffeine, including epidemiological studies, laboratory investigations and tests with volunteers, published in 1989 and 1990. It groups published articles according to observed or investigated biological effects. The most significant findings and differences between studies are pointed out with brief commentaries on the results. The overall assessment for the safety of drinking coffee and the effect of coffee on human health, based on the literature published in 1989 and 1990, indicates that certain controversial issues are still unresolved. PMID- 1500040 TI - [Auto- and hetero-aggression in Gilles de la Tourette syndrome]. AB - A 29-year old patient with Gilles de la Tourette's syndrome exhibited severe compulsive self-mutilation and hostility leading to long-term hospitalisation. A history of refractory self-mutilation increases the risk for suicidal acts, which represent a rare complication in the course of the Tourette disorder. PMID- 1500041 TI - [Musical pseudo-hallucination in acquired hearing loss]. AB - Auditory hallucinations take various forms including the perception of tinnitus, voices, and, rarely, music. While formed hallucinations are usually ascribed to psychiatric illness, we describe a syndrome of musical hallucinations in mentally sane patients, who are hard of hearing or deaf. 26 cases from the literature are supplemented by 6 own observations, including the first description of two cases in a single family. The different modes of emergence, the spectrum of clinical features and their course are outlined. Differential diagnostic, pathogenetic and therapeutic aspects are discussed. PMID- 1500042 TI - [Psychology and psychopathology of firesetting behavior 1955 to 1991--a review]. AB - After a historical introduction and some short remarks on criminal arson, this review of the literature since 1955 mainly focuses on pathological firesetting. It deals with all important aspects of the psychiatry of firesetting: arson by persons referred to psychiatric examination, by the mentally ill, and by psychiatric inpatients, the relationship between arson and sexuality, psychoanalytical contributions, arson by children and juveniles, therapy and prevention of firesetting behaviour. Female arsonists, recidivism, and suicide by burning are considered separately. PMID- 1500043 TI - Why managed care cannot contain hospital costs--without rationing. PMID- 1500044 TI - The political economics of health insurance market reform. PMID- 1500045 TI - Taking the public's pulse on health system reform. PMID- 1500046 TI - Why do hospital costs continue to increase? PMID- 1500047 TI - Bad debt and free care in Massachusetts hospitals. PMID- 1500048 TI - Opportunity costs in modern medicine. PMID- 1500049 TI - Revised trends in states' nursing home capacity. PMID- 1500050 TI - Tracking the progress of academic health centers. PMID- 1500051 TI - Physician supply strategy: the case of the south. PMID- 1500052 TI - Assuring access to health care: the Robert Wood Johnson Foundation strategy. PMID- 1500053 TI - Lessons from implementation of Washington's Basic Health Plan. PMID- 1500054 TI - Administrative costs: answering the critics. PMID- 1500055 TI - The other side of Canada. PMID- 1500057 TI - Pondering the U.S. health system. PMID- 1500056 TI - Bias in, bias out: a reply to Sheils, Young, and Rubin. PMID- 1500058 TI - The shortcomings of voluntarism in the small-group insurance market. PMID- 1500059 TI - Inside the black box of administrative costs. PMID- 1500060 TI - Health and surgical outcomes in Canada and the United States. PMID- 1500061 TI - Mending the flaws in the small-group market. PMID- 1500062 TI - Can all-payer rate setting and the competitive strategy coexist? PMID- 1500063 TI - The price of success: health care in an aging society. PMID- 1500064 TI - Characterization and uses of monoclonal antibody derived against DNA binding domain of the ets family of genes. AB - A monoclonal antibody recognizing ets proteins from a variety of species has been developed. This antibody recognizes ets1, ets2, erg, and other related proteins. It has a high affinity for the ets1 protein. The epitope for the pan ets mAb consists of about 13 amino acids. This antibody can be used to isolate and characterize new members of ets gene family derived from a c-DNA expression library, as well as to identify other "ets motif" binding proteins. PMID- 1500065 TI - Identification of metallothionein in cultured cells by immunoblotting and immunofluorescence using a new monoclonal antibody. AB - A hybridoma clone (MT45-5-3) producing an IgG-class monoclonal antibody specific for metallothioneins (MTs) was established. The monoclonal antibody (MT45) cross reacted with mouse, rat and rabbit Cd(2+)-induced MTs 1 and 2 and Zn(2+)-induced MT 2 as assessed by enzyme-linked immunosorbent assay. When the antibody was used to detect the MTs transferred to nylon membranes after SDS-polyacrylamide gel electrophoresis, the antibody reacted with cultured human cell MTs as well as rat, mouse and rabbit MTs 1 and 2 even after carboxymethylation. The antibody could be used for the indirect immunofluorescence test for Cd(2+)-induced MTs in cultured human and mouse cells. PMID- 1500066 TI - Kinetic and energetic parameters of imipramine binding to monoclonal antibodies as measured by fluorescence spectroscopy. AB - Monoclonal antibodies which bind small drugs are useful for the study of the interactive forces involved in antibody-ligand complexation. Detailed understanding of these supramolecular forces requires a careful examination of structural and thermodynamic parameters of the interacting molecules. Fluorescence spectroscopy techniques are very useful in this regard. We report here, the kinetic and energetic parameters of four monoclonal antibodies made against the tricyclic antidepressant imipramine. These monoclonal antibodies were found to possess high to very high binding affinity constants, ranging from 10(7) to 10(10) M-1, and caused fluorescence quenching or enhancement of a fluorescein labelled imipramine. The dissociation rates of the fluorescent ligand from the complexes were measured at different temperatures in order to provide some insight regarding the kinetic and energetic (thermodynamic) parameters of the antibody-ligand binding interactions. PMID- 1500067 TI - Role of metabolic waste products in the control of cell proliferation and antibody production by mouse hybridoma cells. AB - In order to determine the factors limiting the proliferation and productivity of mouse hybridoma cells in batch/fed-batch cultures, we tested the influence of various environmental parameters on the growth of a model cell line VO 208. We observed that, among the major metabolic waste products, ammonium ions at concentrations superior to that present in the medium at the end of a batch culture do not exert a significant toxic effect on cell growth, whereas in contrast, lactic acid is cytotoxic at concentrations reached in cultures. Feeding of fructose instead of glucose during the stationary phase of the culture markedly prolongs the life span of the culture and enhances the antibody secretion accordingly. However, we failed to observe a satisfactory proliferation pattern in cultures grown in a glucose-free fructose-supplemented medium. We also noted that vitamin supply may be limiting in fed-batch cultures. It thus appears that thorough examination of the cell metabolic needs allows the designing of a culture regimen which significantly improves cell growth and secretion. PMID- 1500068 TI - B-cell hybridoma as intraperitoneal tumor model: correlation between tumor growth and monoclonal antibody production. AB - Murine B-cell hybridoma cells producing an immunoglobulin G1 (K13), specific for human immunoglobulin kappa chains were inoculated intraperitoneally in mice. After intraperitoneal injection of 10(6) K13 hybridoma cells, superficial intraperitoneal implants and ascites developed, resulting in death after 10 +/- 3 days (mean +/- SD). An immunoradiometric assay was developed to measure K13 in murine blood, ascites and culture supernatant. The assay utilized polymer beads coated with human immunoglobulin G. The amount K13 bound to the particles was measured with a 125I-labelled monoclonal rat antibody (LO-MG1-13) specific for mouse IgG1. The assay could be used over a wide working range (2-500 micrograms/l). Kinetic studies suggested that about 10(5) secreting cells were required for detection of K13 in blood. After injection of 10(6) cells, K13 was measurable in blood 1 day later in all animals. Nine of 33 mice injected with 10(5) or less cells survived, and initially showed rising K13 blood levels followed by decreasing blood levels. In conclusion, a close relationship was established between i.p. growth of the hybridoma K13 cell line and the MAb blood levels. The basic concepts of this assay can readily be adopted for other clones with the limitation that pure antigen is needed for solid phase extraction of the MAb from mouse blood. PMID- 1500069 TI - Monoclonal antibodies specific to sailfish serum albumin: development of an assay for the identification of fish species in the field. AB - Balb/c mice were immunized with albumin purified from sailfish (Istiophorus albicans) serum. Hybridomas were produced and screened by ELISA for reactivity with the purified albumins of sailfish, blue marlin (Makaira nigricans) and white marlin (Tetrapturus albidus). Monoclonal antibodies (MAbs) from 16 different clones exhibited activity against sailfish albumin. Thirteen of the MAbs showed cross-reactivity with the marlin species. Three MAbs exhibited distinct specificity for sailfish albumin. One of these species specific MAbs (M2D1) was conjugated to horseradish peroxidase (HRP) in order to construct an ELISA for identification of sailfish from serum. The ELISA for sailfish correctly identified eight sailfish from 26 billfish serum samples. The MAb-peroxidase conjugate was highly specific toward sailfish in that no reaction against heterologous species was detected. PMID- 1500070 TI - Production and characterization of a monoclonal antibody to human saposin C. AB - A murine IgG1 monoclonal antibody, termed 68-12, was produced against purified human saposin C. Immunoprecipitation and binding analysis indicated that the antibody reacted only with saposin C. Dot blotting and Western analysis demonstrated that antibody 68-12 also reacted with prosaposin and a higher molecular weight protein(s) in murine spleen and cerebral grey matter. Solid phase competitive radioimmunoassay against 125I labeled saposin C (0.25 micrograms/ml) showed no cross reactivity for saposin A, B and D up to 15 micrograms/ml. At a concentration of 50 micrograms/ml saposin A, B and D cross reacted 21, 1.5, and 49% respectively. Monoclonal antibody 68-12 appears to have potential utility in the purification, detection and quantitation of human saposin C and its precursor. PMID- 1500071 TI - Production of monoclonal antibodies specific to major allergens of Cryptomeria japonica pollen. AB - Monoclonal antibodies (MAbs) directed against Cryptomeria japonica pollen antigen (CPAg) were prepared. CPAg was precipitated with these MAbs and both MAbs CPA7 (IgG2a) and CPA9 (IgG1) recognized two major glycoproteins (m = 41 kDa and 46 kDa) of CPAg. MAb CPA7 or CPA9 was coupled to CNBr activated sepharose and affinity purification of the major allergen of CPAg from the crude extract was performed. The affinity purified CPAg bound IgE antibody present in patients with Cedar pollinosis. PMID- 1500072 TI - Characterisation of eight monoclonal antibodies to involucrin. AB - Involucrin is a precursor of the insoluble protein envelope that is assembled in the outermost layers of the epidermis. The coding sequence of the protein contains a number of short tandem repeats that have been greatly altered during mammalian evolution. We have characterised eight mouse monoclonal antibodies raised against human involucrin, all of which bind to the protein in immunoprecipitation, immunoblot and immunohistochemical preparations. Each antibody was screened for cross-reactivity with gorilla, owl monkey, dog and pig involucrin and with a fragment of the human protein, expressed in lambda gt 11, that includes the entire early region of the modern segment of repeats. Three antibodies recognised involucrin in all of these assays. Four antibodies recognised primate involucrins and the lambda gt 11 fragment. One antibody, which showed cross-reactivity with lower molecular weight proteins, only recognised primate involucrins and therefore bound outside the early region of the modern segment. Since the antibodies can be used to detect involucrin both biochemically and histologically, in a range of species, they will have applications in further studies of the expression, function and evolution of the protein. PMID- 1500073 TI - Monoclonal antibodies to Escherichia coli beta-galactosidase and their use for detection and purification of recombinant expression products. AB - A panel of seven mouse monoclonal antibodies (BG-01-BG-07) was prepared against beta-galactosidase derived from E. coli. The antibodies are beta-galactosidase specific, show no cross-reactivity with other E. coli proteins and can be used for identification and characterization of beta-galactosidase fusion proteins expressed in lambda expression vectors. One of the antibodies allows a simple, one-step isolation of the fusion proteins directly from the crude bacterial lysates using immunoaffinity chromatography. PMID- 1500074 TI - [Isolation of H. pylori proteins and support for their suitability in serologic diagnoses]. AB - H.pylori-proteins were separated using gel chromatographic methods. These antigens were tested for their suitability to detect H.pylori-specific antibodies. A complex of two proteins (62 kDa and 30 kDa) was a strong and specific antigen. A third protein (13 kDa) was a good but nonspecific antigen. Concerning these facts we compared two often used antigen preparations for serodiagnosing H.pylori-specific antibodies (acid-glycine preparation and sarcosyl-insoluble outer membrane proteins). The sarcosyl-insoluble material contains more specific antigens and lower levels of nonspecific proteins compared to the acid-glycine preparation. Based on these results we conclude that the outer membrane preparation seems to be more suitable for the serodiagnosing of H.pylori-specific antibodies. PMID- 1500075 TI - [Alterations in lymphocyte subsets in variable immunodeficiency syndrome]. AB - Besides functional defects, different phenotypical alterations of lymphocytes have been described in patients with CVID. A decrease in LAM-1- (= Leu8) and CD21 expression was observed on B cells. Some patients with CVID show alterations in their T-cell subpopulations: The most striking features of this subgroup are low CD4/CD8-ratio, an increase in CD57/CD8 double-positive lymphocytes, and a strong enhancement of HLA-DR and "memory" markers such as CD29 and LFA-3 on T cells. PMID- 1500076 TI - [Pentoxifylline--an inhibitor of the synthesis of tumor necrosis factor alpha]. AB - The growing knowledge on the pathophysiological role of cytokines in acute and chronic inflammatory processes stimulated efforts to control their synthesis and action pharmacologically in clinical situations. Recently, in our institute evidence was raised that pentoxifylline (POF) is able to suppress the synthesis of tumor necrosis factor-alpha (TNF) in cell cultures, in vivo, and to protect experimental animals against endotoxin shock. Studies in human experimental endotoxemia showed that pentoxifylline decreased circulating TNF without affecting endogenous formation of interleukins. The potency of this drug to interfere with TNF synthesis could also be demonstrated in cases of acute and chronic cytokine release syndromes such as OKT3 first-dose reaction and severe pulmonary tuberculosis, respectively. We suggest that POF may improve therapeutic strategies in various diseases in which TNF was identified as a causative pathophysiological factor. PMID- 1500077 TI - [Impaired induction of chemiluminescence and function of polymorphonuclear neutrophilic granulocytes in diabetes mellitus]. AB - The aim of this study was to investigate PMN-chemiluminescence response as a measure of respiratory burst activity and the phagocytic PMN function "ingestion" with regard to metabolic control parameters in diabetes mellitus (d.m.) in comparison to healthy controls. Our findings demonstrated a significant reduction of chemiluminescence response and ingestion in diabetic patients compared to controls (p less than 0.01 resp.); further an inverse relation of metabolic control parameters in d.m. and PMN impairment, suggesting inhibitory effects on PMN function, thus leading or contributing at least in part to altered host defense. PMID- 1500078 TI - [Epidemiology and pathogenesis of streptococcal infection]. AB - The appearance of the "streptococcal toxic shock-like syndrome" led to a growing interest in infections caused by Streptococcus pyogenes (group-A-streptococci). Since 1987 some 800 cases with a lethality of 20% or more were observed. Contrary to toxic scarlet fever the site of primary infection are the lower respiratory tract or soft tissue infections. Erythrogenic toxins and low molecular weight mitogens, inducing cytokines (IL-2, IL-3, IL-6, TNF-alpha, IFN-gamma) seem to be involved in the pathogenesis of these severe infections. Morphologically and culturally the strains isolated from cases of toxic shock-like syndrome cannot be differentiated from isolates of epidemic scarlet fever or sporadic cases. At the same time, when in Scandinavia an epidemic by S.pyogenes type 1 with many cases of toxic shock was observed, the same type caused a scarlet fever epidemic without complications in eastern Germany. Erythrogenic toxin type A or its toxoid, respectively, can be used for successful immunizations of rabbits. Another--antibacterial-immunization can be done with the M-protein of S.pyogenes, which is limited by its type-specificity. Streptococcal vaccination is required especially for developing countries with a high incidence of rheumatic fever. Infections due to Streptococcus agalactiae (group-B streptococci) are often underestimated though they have a first position in septicemia and meningitis of newborns. Taxonomy and nomenclature of streptococci are often changing; a list of the presently known species is presented in table I. PMID- 1500079 TI - Intestinal intraepithelial lymphocytes and lymphoepithelial interactions in the human gastrointestinal mucosa. AB - Although representing a major immunological apparatus, it is not known how the immune system of the intestinal mucosa differentiates between dietary antigens (resulting in systemic tolerance) and potential pathogens. It is thought that intraepithelial T lymphocytes (IEL) may play a central role in local intestinal immunity and are likely to be important in immunity to gastrointestinal neoplasms and rejection responses to gut allografts. However, the biology of IEL and their unusual immunological microenvironments in the gastrointestinal mucosa are little understood. IEL are predominantly CD8+ TcR alpha beta+ CD3+ T cells which differ from lamina propria and peripheral T cells in many respects. IEL show low expression of CD5, CD6, LFA-1 (CD11a/CD18) and VLA-4, and high expression of HML 1. TcR gamma delta + IEL, although a minority population, are also phenotypically distinct, insofar as they are 50% CD8+, mainly V delta 1+ V gamma 9- and CD4- CD5 . IEL show poor proliferative responses to PHA, anti-CD3 and phorbol ester/calcium ionophore in vitro and have no clear functional role: they neither provide helper nor suppressor functions for Ig synthesis by B cells and do not mediate spontaneous cytotoxicity. However, there is evidence that IEL show preferential activation in response to sheep erythrocytes, presumably signalling via CD2. As normal and inflamed intestinal epithelia do not express ICAM-1, it seems unlikely that the LFA-1/ICAM-1 interaction is of importance to IEL activation. Rather, the CD2 (LFA-2) interaction with LFA-3 expressed by enterocytes may serve both to anchor IEL and to provide an accessory stimulus for activation. Nevertheless, the questions of antigenic specificity and immunological role remain unanswered. PMID- 1500080 TI - Monoclonal antibodies against metallothioneins from the human liver. AB - Six hybridomas secreting monoclonal antibodies directed against human fetal liver metallothioneins (MTs) have been generated and characterized. One antibody, K5A6, was specific for MT-1, the others recognized all isoMTs present in the human fetal liver. Each of these antibodies showed a unique cross-reactivity pattern when tested with MTs from the livers of different mammals. A double-antibody sandwich enzyme-linked-immunosorbent-assay (ELISA) was developed with the antibodies L2E3 and L5G2. This assay allows the detection of 60 pg human fetal liver MT and exhibits a metal dependent response for Zn-, Cd- and Hg-MT. PMID- 1500081 TI - Isotypic and allotypic analysis with monoclonal antibodies and jacalin of 309 serum monoclonal IgA from French and Japanese myeloma patients. AB - The subclass and allotype distribution of serum monoclonal IgA from myeloma patients was determined by ELISA with monoclonal antibodies in two French and one Japanese laboratory. In addition, the French sera were tested for their reactivity with the lectin jacalin. No significant difference in the isotypic distribution between French and Japanese series could be demonstrated: kappa/lambda ratios were 0.99 and 1.17, and the IgA1 subclass accounted for 93.9% and 91% of cases in the French and Japanese studies, respectively. Five out of 7 myeloma IgA2 from Japan and only one of the 12 IgA2 from France belonged to the A2m(2) allotype (P less than 0.01). All 219 IgA1 tested reacted with jacalin by immunoelectrophoresis (IEP), although with variable intensities. Among IgA2 proteins, only one (of the A2m(1) allotype) yielded a precipitating line with jacalin by IEP. Molecular analysis demonstrated that this protein was an IgA1 IgA2 hybrid bearing most of the A2m(1) epitopes. PMID- 1500082 TI - The human lymphokine leukoregulin induces cell resistance to complement-mediated lysis. AB - Leukoregulin (LR) is a lymphokine secreted by human natural killer (NK) cells. Its effect on the susceptibility of K562 human erythroleukemic cells to lysis by antibody and complement was examined. As reported here, treatment of K562 cells with LR for 60 min at 37 degrees C confers on them resistance to complement damage. The LR-induced state of complement resistance is transient and the cells recover within 4-6 h unless a second dose of LR is added. The protective action of LR was observed using both conventional 51Cr-release and trypan blue inclusion assays. The protein synthesis inhibitors puromycin and cycloheximide and the protein kinase inhibitors tamoxifen, polymyxin B and W-7, could each block this action of LR. Fewer membrane attack complexes were found, following complement activation, on LR-treated than control cells. These results suggest that LR increases the capacity of K562 cells to down-regulate complement activation or repair the complement damage, possibly by inducing synthesis of defense proteins and/or activation of protective protein kinases. PMID- 1500083 TI - Purification of a novel B cell growth and differentiation factor associated with lupus syndrome. AB - We have previously reported that KML1-7 cells cloned from a lupus-prone MRL/l mice produced a soluble factor that preferentially expanded anti-DNA antibody production across the H-2 barrier. We purified this factor, a 55-kDa protein that we termed nucleobindin (Nuc). Nuc showed not only induction of anti-ssDNA IgG antibody in cultures of B cells from MRL/l mice (greater than 16 weeks old), but also growth activity. Furthermore, antibodies against existing cytokines have so far not been shown to block Nuc activity on these B cells. In view of the fact that Nuc did not boost anti-ssDNA IgG antibody production in cultures of spleen cells of comparable age from MRL/n mice, which develop a mild form of lupus after the age of one year, Nuc may act on pre-activated B cells to help IgG anti-DNA antibody production. Taken together, Nuc is a new kind of growth and differentiation factor associated with lupus syndrome. PMID- 1500084 TI - Synthetic peptides comprising defined sequences of CH-2 and CH-3 domains of human IgG1 induce prostaglandin E2 production from human peripheral blood mononuclear cells. AB - Synthetic peptides Y48 and Y75 comprising sequences at exposed sites within the CH-2 and CH-3 domains of human IgG1 at a concentration of 10(-5) M, increase PGE2 production by human peripheral blood mononuclear cell (PBMC) cultures. An increase of leukocyte migration inhibitory factor (LMIF) production in PBMC cultures--as a result of synthetic peptide treatment--was also observed. This LMIF activity, to some extent, is attributed to the PGE2 production by the cells; the inhibition of leukocyte migration being abolished by the presence of indomethacine or antibody to PGE2. PMID- 1500085 TI - Gut mucosal lymphocyte subpopulations in the host-defence of Shigella infected guinea-pigs. AB - Lymphocyte subpopulations from the gut mucosa were studied in Shigella susceptible guinea-pigs to evaluate their role in mucosal immune responses to such organisms. Four weeks after infection, isolated lymphocytes were characterised by an immunofluorescent technique. The increase in the T cell intra epithelial population was less (48%) in comparison to that in normal uninfected animals (74%). On the other hand, Ig bearing B cells in the lamina propria showed an increased incidence and more than 15% of the total mucosal lymphocytes lacked any surface marker, which indicated that they were non-T and non-B cells. A significant rise in the intraepithelial T cell population (P less than 0.01) was observed 6 weeks after infection in comparison to that observed after 4 weeks. PMID- 1500086 TI - Antibodies to CD46 in pregnant women. PMID- 1500087 TI - IP-10, a gamma-interferon-inducible protein related to interleukin-8, lacks neutrophil activating properties. AB - IP-10, a small, gamma-interferon-inducible protein with structural homology to interleukin-8 (IL-8), was prepared by automated chemical synthesis and compared with synthetic IL-8, GRO alpha and neutrophil-activating peptide 2 (NAP-2) for neutrophil stimulating activity. The following functions were tested: cytosolic free calcium changes, chemotaxis in vitro, respiratory burst, exocytosis of azurophil and specific granules from cytochalasin B-pretreated cells, and competition for IL-8 receptor binding. At 1, 10, 100 and 1000 nM, IP-10 was inactive in all assays, in contrast to the reference peptides which exhibited the expected neutrophil stimulating effects. In addition, IP-10 did not induce neutrophil accumulation after intradermal injection in rats, and did not act as IL-8 antagonist. PMID- 1500088 TI - Enhancement of lymphocyte proliferation by mouse glandular kallikrein. AB - Mouse glandular kallikrein (mGK) strongly enhanced the spontaneous and mitogen induced proliferation of lymphocytes. Both blast formation and 3H-TdR incorporation were dose-dependently enhanced at the same time many cells were killed. The enhancing activity was independent of EGF, because EGF-binding proteins (mGK-9 in mGK-6,9 mixture and mGK-13), renal kallikrein (mGK-6) and human kallikrein all displayed the same enhancement. A serine proteinase inhibitor, diisopropyl fluorophosphate, could block the enhancement by mGK. The new function suggests that mGK is important in the immune system as a regulatory molecule. PMID- 1500089 TI - Human immunodeficiency resulting from a maturational arrest of germinal center B cells. PMID- 1500091 TI - Antigen-induced inhibition of the autoimmune response to rat male accessory glands: bone marrow dependence of the enhancement of IA+ but not IE+ antigen presenting cells. AB - IE+ peritoneal cells (PC), involved in the induction of suppression of autoimmune response to rat male accessory glands (RAG), are obtained from rats 2 h after i.p. injection of a purified fraction (FI) of RAG (FI-PC2h). In contrast, IA+ PC, involved in the induction of autoimmune response to RAG, are obtained from rats 24 h after FI of RAG injection (FI-PC24h). The present report analyzes the effect of irradiation or irradiation/bone marrow reconstitution on the induction of both populations of PC. Peritoneal cell donor rats were irradiated in a telegamma therapeutic Cs137. Twenty hours later half of them were i.v. reconstituted with 40 x 10(7) bone marrow cells. Six days later rats were i.p. injected with 200 micrograms of FI of RAG and 10(7) resident PC. The PC were harvested 2 h or 24 h later. The ability of resident PC to yield IE+ FI-PC2h involved in the induction of suppression is not impaired by irradiation, but the ability of resident PC to yield IA+ FI-PC24h involved in the induction of a positive response is impaired by irradiation and restored by bone marrow reconstitution of irradiated rats. Culture of normal PC with FI of RAG for 2 h or 24 h shows a selective increase in IE+ cells able to induce suppression to RAG.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1500090 TI - G protein mediated signal transduction: membrane immunoglobulin associated phosphoproteins identified in octyl-beta-glucoside lysates of normal B cells. AB - Several recent studies have shown that the antigen receptors (mIgM and mIgD) on normal B cell surfaces are part of larger multimolecular complexes, as each is noncovalently coupled to at least two other proteins whose phosphorylation is inducible upon G protein activation. However, B cell receptor complexes appear to be extremely labile, so that extraction of membrane immunoglobulin (mIg) from cell lysates in physical association with noncovalently coupled proteins has been shown to be highly dependent on the choice of detergent. Recent progress has to a large extent been dependent upon the introduction of digitonin, a detergent in which B cell receptor complexes are at least partially stable, as an agent to solubilize B cell membranes. Studies presented here demonstrate that if another well known detergent, octyl-beta-D-glucopyranoside (octyl glucoside), is utilized in place of digitonin, mIg receptors are immunoprecipitated from B cell lysates in association with several newly identified proteins, whose phosphorylation is also G protein dependent. In particular we find three to four mIg associated phosphoproteins in the molecular weight range of 47 to 57 kDa, and at least two others at 82 and 112 kDa. Some of these proteins may correspond to polypeptides that have been functionally linked to mIg dependent signal transduction, but have not as yet been shown to be physically coupled to the receptor. PMID- 1500092 TI - Defect in generation of LAK cell activity under oxygen-limited conditions. AB - In general, the in vitro induction of lymphokine activated killer (LAK) cell activities by interleukin 2 (IL-2) in human peripheral blood mononuclear cells (PMNC) has been performed in an atmosphere of 5% CO2 in air (20% O2), whereas IL 2-induced LAK cell activities are considerably reduced under concentrations of 5% O2 equal to arterial blood oxygen tension (100 mmHg) and 2% O2 equal to venous blood oxygen tension (40 mmHg). Cultured cell viability, IL-2 receptor-beta expression on large granular lymphocytes (LGL), the percentage of IL-2 receptor beta positive LGLs and cell proliferation were not affected by oxygen-limited conditions. LAK cells were induced by IL-2 over 5 days at 20% O2, at which time the LAK cells were further stimulated by IL-2 in 2% O2 and 20% O2. Under these conditions the activity of LAK cells in 2% O2 decreased day by day, while that of LAK cells induced in 20% O2 was maintained at least until day 10 of the original culture. LAK effector cell-mediated lysis was not influenced by oxygen-limited conditions. These results point to more successful applications of the combination of oxygen therapy and adoptive cellular immunotherapy in the clinic. PMID- 1500093 TI - Haemolysis mediated by anti-D monoclonal antibodies in direct and cold target competition ADCC assays. AB - Thirteen IgG anti-D human monoclonal antibodies (mAbs) were compared for their ability to mediate lysis of D-positive erythrocytes by PBMC in direct and cold target competition antibody-dependent cell-mediated cytotoxicity (ADCC) assays. In the latter assay, lysis of fluid-phase anti-D-sensitised O Rh D-positive papainised erythrocytes (E-IgG) was inhibited by A (or B) Rh D-negative papainised erythrocytes sensitised by fluid-phase anti-A (or anti-B) mAbs. The competitive and lytic activities of the anti-D mAbs were characterised by the equilibrium dilution (ED) values, which were the reciprocal of the dilution of anti-A (or anti-B) at which lysis of target E-IgG and competitor E-IgG were identical. There was a poor correlation between the number of erythrocyte-bound anti-D molecules and either the sensitivity of E-IgG anti-D to haemolysis in the direct ADCC assay, or to the ED values of the mAbs obtained in the cold target competition ADCC. The discriminatory power of the cold target competition ADCC was better than than of the direct ADCC to detect differences in the lytic potential of the anti-D mAbs. PMID- 1500094 TI - Suppression of antibody responses in rats to murine anti-CD4 monoclonal antibodies by conjugates with monomethoxypolyethylene glycol. AB - The effectiveness of therapeutically relevant xenogeneic monoclonal antibodies (MoAb) may be counteracted by their inherent immunogenicity. Since conjugates of diverse proteins with mono-methoxypolyethylene glycol (mPEG) were shown to induce Ag-specific tolerance in mice and rats, we used outbred rats in this study as an experimental model for establishing the tolerogenicity of mPEG conjugates of murine MoAb. The results demonstrate that: (i) murine anti-rat CD4 MoAb (W3/25) were more immunogenic than murine anti-human CD4 MoAb (MAX.16H5) in rats; (ii) W3/25 preferentially induced an anti-idiotypic (anti-id) antibody response; and (iii) antibodies to both common and idiotypic determinants could be suppressed in rats by treatment with W3/25(mPEG)28. PMID- 1500095 TI - Identical point mutation leading to low levels of mannose binding protein and poor C3b mediated opsonisation in Chinese and Caucasian populations. AB - A common opsonic defect occurring in 7% of the Caucasian population is associated with low serum levels of the lectin mannose binding protein (MBP). This study sought to determine whether the deficiency was also present in a Chinese population using sera obtained from 100 healthy Chinese children (age range 6 weeks-16 years). The distribution profiles of MBP levels and C3b/C3bi fragments binding to mannan coated plates were both bimodal and similar to the corresponding Caucasian profiles. Serum MBP levels were low in 9% of the Chinese children and all of these sera generated low levels of C3b/C3bi fragments. Overall there was a high significant correlation between MBP levels and C3b opsonin generation (r = 0.77; P less than 0.001). By analogy with similar findings in a Caucasian population we believe this correlation to be a reflection of antibody independent complement activation by MBP. In a pilot study of DNA obtained from three adult Chinese with low MBP levels the point mutation causing MBP deficiency in Caucasians was identified in all three cases. PMID- 1500096 TI - Recombinant human interleukin 1 beta and tumor necrosis factor affect glycosylation of serum alpha 1-acid glycoprotein in rats. AB - Serum concentration and glycosylation of rat alpha 1-acid glycoprotein (alpha 1 AGP) were evaluated after the in vivo administration of recombinant human interleukin-1 beta (rhIL-1 beta) and tumor necrosis factor alpha (rhTNF-alpha), alone or associated. The effect of LPS and turpentine was also studied. In all models, serum alpha 1-AGP concentrations were increased and glycosylation was altered. The alpha 1-AGP levels reached 1.8 g/liter with cytokines alone, 2.1 g/liter with cytokines associated or LPS, and 3.4 g/liter with turpentine. Analysis by concanavalin A (Con A) affinoimmunoelectrophoresis (CAIE) revealed that the relative proportion of Con A unreactive form always decreased whatever the inducing agent. On the other hand, the resulting effect on the concentrations of Con A unreactive alpha 1-AGP concentrations was an increase with cytokines alone or LPS and a decrease with cytokines associated or turpentine. These results suggest a dissociation between the alteration in the level of alpha 1-AGP synthesis and in the pattern of its glycosylation in the various inflammatory models. PMID- 1500097 TI - Prekallikrein activation in human, bovine, and rabbit plasmas: presence of an inhibitor in bovine plasma. AB - Contact of human plasma with a negatively charged surface such as dextran sulfate activates prekallikrein to kallikrein, which releases the vasoactive peptide bradykinin from high-molecular-weight kininogen. The dextran sulfate-induced activation of prekallikrein at 0 degree C (assayed by its amidolytic activity on the chromogenic substate S-2302) could not be observed in either bovine or rabbit plasmas when compared to human plasma. Neither bovine nor rabbit plasma inhibited the amidolytic activity of contact-activated human plasma at 0 degrees C. The activation of prekallikrein in human plasma was significantly inhibited by the addition of bovine plasma but not by rabbit plasma. Bovine plasma (0.025 units, 1 unit = 1 ml of plasma) caused 68.8% inhibition of prekallikrein activation. Eighty percent of the inhibitory property of bovine plasma was present in the greater than 30,000-molecular-weight fraction. These results indicate the presence of an inhibitor(s) of prekallikrein activation in bovine plasma. PMID- 1500098 TI - Comparison of oxidant production by bovine neutrophils and monocyte-derived macrophages stimulated with Brucella abortus strain 2308. AB - Oxidant production by bovine monocyte-derived macrophages and neutrophils was compared after stimulation with phorbol myristate acetate (PMA), opsonized zymosan (OZ), and B. abortus opsonized with naive-autologous, reactor, or fetal bovine sera. Neutrophils responded more rapidly to all stimuli and produced up to 100-fold greater oxidant than did equal numbers of bovine monocyte-derived macrophages. Macrophages and neutrophils stimulated with PMA, OZ, and reactor opsonized B. abortus had higher mean oxidant production than phagocytes exposed to B. abortus opsonized with autologous sera, fetal bovine serum, or nonopsonized bacteria. Stimulation of macrophages by opsonized zymosan, buffer, and B. abortus opsonized with autologous sera, reactor serum, or fetal bovine serum resulted in low levels of oxidant production that were not significantly different. Only PMA caused a significantly higher level of oxidant production by macrophages. PMID- 1500101 TI - Information support for MCH. PMID- 1500099 TI - Arachidonic acid metabolites: effects on inflammation of fetal rabbit excisional wounds. AB - Uncovered fetal rabbit excisional wounds do not exhibit any classic signs of healing; wounds covered with an impermeable cover do contract, reepithelialize, and exhibit inflammation. Prostaglandin E2 (PGE2) is elevated in amniotic fluid, acting as an immunosuppressant at the maternal-fetal interface. Full-thickness excisional wounds were made on 25-day gestational age rabbit fetuses. Half the wounds were covered with an impermeable cover. Tissue from covered, uncovered, and nonwounded fetuses was examined 72 h after wounding for arachidonic acid metabolites. Uncovered wounds had significantly (P less than or equal to 0.05) elevated levels of PGE2, PGF2 alpha, and 12-HETE versus covered wounds and control tissue. Covered wounds had significantly elevated levels of 15-HETE compared to uncovered and control tissue. The elevated PGE2 in uncovered wounds may act as a fetal immunosuppressant; covered wounds (lower PGE2) developed cellular inflammation. Further investigations of these interactions may permit modulation of adult inflammation. PMID- 1500100 TI - Present status of neonatal care in India. PMID- 1500102 TI - Hematocrit and whole blood viscosity in newborns: analysis of 100 cases. AB - Hematocrit (Hct) and whole blood viscosity was studied at a mean age of ten hours in 100 neonates. Group A (n = 25), were term normal newborns, Group B (n = 25) were preterms, Group C (n = 20) were term small for gestation (SGA) and Group D (n = 30) had perinatal hypoxia. Blood viscosity was estimated in all cases at shear rates 94.5, 51.2, 20.4 and 8.1 and intergroup variability in viscosity compared at shear rate 51.2. The mean hematocrit (Hct) (59.4%) and viscosity (8.2 cps) was higher in Group A as compared to other groups, but the difference was not significant (p greater than 0.05). The upper limit of viscosity in Group C (11.9 cps) was higher than in all other groups but this difference was also not significant (p greater than 0.05). With decrease in shear rates a reciprocal increase in viscosity was noted in all four groups. Seventeen neonates (17%) had polycythemia of which eight (47.5%) were SGA. Twelve per cent preterms were polycythemic. Only 3% of neonates had hyperviscosity. The mean Hct and viscosity of the 17 cases with polycythemia was 70.9 and 9.21 cps, respectively, which was significantly higher than mean Hct and viscosity of Group A (p less than 0.05). Partial exchange transfusions were done in five neonates with Hct greater than 75%, of which only one had hyperviscosity. Post-exchange viscosity was not estimated. Whereas, three neonates with polycythemia were symptomatic, none of these had hyperviscosity. A linear correlation between Hct and viscosity was observed (r = 0.67). PMID- 1500103 TI - Correlation of plasma color index with serum bilirubin in neonatal hyperbilirubinemia. AB - In this study, a simple method was evaluated for serum bilirubin estimation in neonates. The color of plasma was compared with various dilutions of potassium dichromate. Readings were then compared with serum bilirubin levels obtained by diazo reaction. The coefficient of correlation (r = 0.7947) between the two was statistically significant. It is concluded that the color index provides reliable estimates of serum bilirubin levels. PMID- 1500104 TI - Reliability of capillary blood gas estimation in neonates. AB - In order to compare the reliability of capillary blood gases to the arterial blood gases, we studied fifty one neonates with moderate birth asphyxia. A significant difference (p less than 0.05) was found between the capillary and the arterial blood gas values with respect to blood pH, PCO2 PO2 and oxygen saturation. However, the levels of blood bicarbonate as assessed by the 2 samples were comparable. Capillary blood gas values are unsatisfactory indicators of the arterial blood gas values and may result in inappropriate management. PMID- 1500105 TI - Thermoregulatory alterations as a marker for sepsis in normothermic premature neonates. AB - To evaluate the core-peripheral temperature alterations as a marker for sepsis in normothermic premature newborns, 50 normal term neonates and 11 preterms with sepsis and 11 normal preterms (controls) were studied. Axillary, rectal and sole temperatures were recorded in all babies using a single mercury-in-glass thermometer by a single observer. There was significant widening of the rectal sole and axillary-sole temperatures in the preterms with sepsis (p less than 0.001). There was no significant difference (p greater than 0.05) between the axillary and rectal temperatures in the term, normal preterms or those with sepsis. With an overall accuracy of 90.9%, a rectal-sole temperature difference of greater than or equal to 2.3 degrees C (100% sensitivity) or greater than or equal to 3.2 degrees C (100% specificity) is a useful marker to differentiate normothermic preterms with or without sepsis. Using the axillary-sole temperature difference, the respective values were greater than or equal to 2.2 degrees C and greater than or equal to 3.0 degrees C. PMID- 1500106 TI - Effect of pregnancy associated hypertension on immunoglobulin levels in newborns. AB - In a prospective study of 124 neonates born to mothers with normal pregnancy and pregnancy associated hypertension (PAH), serum IgG, IgA and IgM were estimated by single radial immunodiffusion technique. Significantly low levels of IgG were found in mothers having PAH, as compared to normal pregnancy (p less than 0.001), whereas IgA and IgM showed no difference in the two groups. There was no statistical difference in maternal and cord blood IgG in either the control or study group. IgG was significantly higher (p less than 0.001) in cord blood of babies born by vaginal route as compared to forceps (via vaginal route) or cesarean section. IgA and IgM levels did not vary with mode of delivery. PMID- 1500107 TI - A new transport incubator for primary care of low birth weight babies. AB - A new portable, cheap and indigenous incubator made of polystyrene has been devised for delivery of primary health care services to the newborn babies in the community. Twenty six babies with a mean weight of 1726 g (range 1388-1981g) and gestational age of 35.3 weeks (range 34-38 wks) were continuously evaluated for 2 hours observation period, in naked and clothed conditions. Rectal, abdominal skin, foot, ambient air and nursery temperatures were recorded. The baseline core temperature of the babies was 36.58 (+/- 0.21) degrees C; after incubator care it was recorded s 36.80 (+/- 0.10) degrees C in naked infants. The baseline core temperature of the clothed babies was 36.63 (+/- 0.21) while it was 37.01 (+/- 0.18) after 2 hours of incubator care. An ambient air temperature of 33-34 degrees C in the incubator (thermoneutral temperature range for these babies being 31.0-33.8 degrees C) was achieved within 30-60 minutes of incubator stay (nursery temperature being 28 +/- 0.6 degrees C). No evidence of carbon dioxide narcosis, hypoxia, acidosis, or adverse thermoregulatory behavior was observed. One baby had hypoglycemia (blood sugar less than 35 mg/dl) and another had sweating. There is a scope for providing additional facilities like administration of oxygen, phototherapy, X-rays through the incubator without disturbing the baby. PMID- 1500108 TI - Growth and behavior development in rural infants in relation to malnutrition and environment. AB - A group of 224 children from a rural cohort of 625 children registered from 1981 to 1983 in 10 villages of KV Block, Varanasi was assessed for morbidity, physical growth, and behavior development (Gesell's developmental schedule). By first birthday children of normal nutrition grade were reduced to one fourth and numbers in Grade II and III malnutrition doubled. This deterioration in nutritional status was probably due to high morbidity, i.e., gastrointestinal, respiratory infections, etc. The skull circumference was 43 cm at the age of one year, being lower by 3 cm than the average size. Children having Grades II and III malnutrition showed poor development in all the areas of behavior, i.e., motor, adaptive, language and personal social. Besides malnutrition, environmental factors like mother's involvement in teaching, encouraging the child, talking to him or being within the visual range; the parental education, their caste and the child's birth order contributed significantly to the development of the child during infancy. PMID- 1500109 TI - Anti-nuclear antibody positivity in multi-transfused thalassemia major. AB - The frequency of anti-nuclear antibodies (ANA) was evaluated in multi-transfused patients of thalassemia major. Twelve out of 83 patients (14.5%) had positive ANA at titres of 1:80 or above. The results were compared with age and sex matched healthy controls who showed positive results in only 1 of 52 cases (1.9%; p less than 0.05). Antibody against double stranded DNA was absent. ANA positivity was found to correlate with higher age (p less than 0.01), more amount of blood transfused (p less than 0.01), splenectomy status (p less than 0.01), higher levels of serum ferritin (p less than 0.01) and presence of hepatitis B surface antigen (p less than 0.01) and antihepatitis C antibody (p less than 0.01). PMID- 1500110 TI - Clinical and etiological profile of acute viral hepatitis. AB - There is a paucity of data on the incidence of sporadic viral hepatitis in Indian children. Clinical, biochemical and etiological profile of 54 patients with acute viral hepatitis was evaluated. Of these, 32 (59.25%) patients had Hepatitis A, 18 (33.33%) had NANB, 2 (3.7%) had Hepatitis B and 2 (3.7%) concurrent Hepatitis A and B infection. It was not possible to distinguish the etiological agents on the basis of the clinical and biochemical profile. Fulminant hepatitis was documented in 8 (14.8%) cases. Children with NANB infection were at a greater risk (p less than 0.05) of developing fulminant hepatitis as compared to Hepatitis A infection. PMID- 1500111 TI - Internipple distance in the newborns. PMID- 1500112 TI - Effect of general and spinal anesthesia on neuro-behavioral responses in cesarean babies. PMID- 1500113 TI - Retinopathy of prematurity--a preliminary report. PMID- 1500114 TI - Anorectal anomaly (low) with imperforate hymen in a newborn. PMID- 1500115 TI - Adrenoleukodystrophy. PMID- 1500116 TI - Spigelian hernia. PMID- 1500117 TI - Duffy blood group and thalassemia major patients in relation to post transfusion malaria. PMID- 1500119 TI - Cerebral granulomatous candidiasis in a neonate. PMID- 1500118 TI - Street heroin poisoning in a seven-month-old infant. PMID- 1500120 TI - Colostrum feeding of healthy newborns. PMID- 1500121 TI - Nutritional beliefs among Anganwadi workers. PMID- 1500122 TI - Undergraduate pediatric education in India. PMID- 1500123 TI - Testing a test. PMID- 1500124 TI - Poliomyelitis--surveillance in India. PMID- 1500125 TI - Health effects of consanguinity in Pondicherry. AB - Of 1000 pregnant women studied, consanguinity was observed in 30.8%, with a higher frequency among women from rural areas, and among Hindus. In the consanguineous group, first cousin marriages were present in 47.4%, and uncle niece marriages in 23.4% of women. Coefficient of inbreeding was highest in Harijans (0.0258), followed by non-Brahmins (0.0220) and Brahmins (0.0204). Fertility was not influenced by consanguinity. There was a significantly higher rate of still births and infant mortality in consanguineous matings as compared with non-consanguineous. Total morbidity was higher in the consanguineous group as compared with the non-consanguineous (p less than 0.01), especially that due to neonatal infections and jaundice. There was no significant difference in the prevalence of congenital malformations, chromosomal and genetic disorders between the two groups, although the number of abnormal births in this group was small. PMID- 1500126 TI - Neonatal gastrointestinal perforations. AB - Fourteen neonates presented with clinical and radiological evidence of gastrointestinal perforation, of which 13 were treated by operative intervention. No infant was formula fed, had rectal bleeding or radiological evidence of pneumatosis intestinalis. Operative findings revealed localized perforation in ten of which three were gastric, two distal ileal, three cecal and two in sigmoid colon. Gangrene with extensive perforation of jejunum, ascending colon and transverse colon were seen in one each. Blood cultures were positive in four, one grew E. coli and three Klebsiella while peritoneal cultures were positive in six, one grew E. coli and five Klebsiella. Ten neonates survived and are being followed up. Three of the four cases who died had white blood cell count greater than 25 x 109/L and grew Klebsiella on peritoneal culture. Factors predisposing to gastrointestinal perforations in neonates are discussed, emphasis is made on the cautious use of umbilical, gastric and rectal catheters, and the need for early surgical intervention. PMID- 1500127 TI - Nosocomial rotavirus diarrhea in two medical wards of a pediatric hospital in Calcutta. AB - One hundred eighty nine children suffering from different medical problems were admitted in two wards of a pediatric hospital in Calcutta during the period between November 18, 1985 and February 10, 1986. Amongst them, 36 children developed nosocomial diarrhea and rotavirus was detected from 80.5% of the cases. The nosocomial rotavirus diarrhea cases had lesser frequency of stools and only mild dehydration but the course of illness was longer in comparison to that of the hospitalized rotavirus diarrhea cases. There is a possibility of spread of infection via fomites, environmental surfaces and most likely mothers. PMID- 1500128 TI - Causes of mortality in children with acute lymphocytic leukemia. AB - Fifty five deaths between January, 1982 to September, 1989 in children with acute lymphoblastic leukemia (ALL) were evaluated to determine the cause of mortality. Fifty cases died during remission. Infection alone was responsible for death in 26 of 55 (47.3%) cases while hemorrhage was seen in 7 (12.7%) children. Infection and hemorrhage together were responsible in another 13 cases. Gastrointestinal tract and pulmonary system were the major sites of bleeding. Infections either alone or in combination with other factors were responsible for death in 42 of 55 (76.5%) of children. Septicemia (n = 11), gastrointestinal (n = 15) and pulmonary infections (n = 10) and meningitis in 2 cases were the major sites of infections. Pseudomonas and Klebsiella in 6 cases each accounted for 54.5% of isolates. PMID- 1500129 TI - Blood pressure levels in south Indian adolescents. AB - The present study was undertaken to develop normative data for the blood pressure (BP) levels in adolescent boys and girls aged 10-17 years residing the rural and urban areas of North Arcot Ambedkar District, Tamil Nadu State. Blood pressures were evaluated as part of an ongoing study on growth and development in adolescents. A total of 7028 BP measurements collected cross-sectionally were subjected to statistical analysis. The mean systolic (SBP) and diastolic (DBP) blood pressure levels were elevated in rural children as compared to that in urban children of respective sexes during 10 and 15 years of age. The mean BP levels were higher in both the rural and urban girls as compared to their male counterparts till the age of 15, after which the trend was reversed. While the mean SBP and DBP levels for rural children of either sex were stable over the age range considered, those for urban children exhibited consistent increase with age. In urban boys, the yearly mean increments in SBP and DBP were 2.5 mm Hg and 2.0 mm Hg and that in urban girls 2.4 mm Hg and 1.7 mm Hg, respectively. It is suggested that perhaps stress factors are responsible for the elevated mean BP levels among the rural adolescents as they are generally engaged in activities that exert considerable physical and psychological stress. PMID- 1500130 TI - Age independent anthropometric index for identifying undernourished children in the age group 5-10 years. AB - An age-independent anthropometric index to identify undernourished children in the age group of 5-10 years is described. Employing a mathematical approach (linear regression analysis) on data from 238 children, the index was derived to be wt/(ht)2. Employing this index, a classification rule for identifying the undernourished was evolved, using as the 'Gold standard' a WHO classification based on NCHS standards. The sensitivity of the classification rule was 95%, the specificity was 92% and the overall efficiency was 92%. PMID- 1500131 TI - Errors in medication in a pediatric ward. AB - Iatrogenic errors in medication were studied in a busy pediatric ward. The study was based on voluntary reporting of errors noticed by the doctors and nurses in the ward. The error rate was 6.4%. Prescription errors accounted for 37.7% of the errors and 2 of these were potentially fatal. Dispensing errors and missed dosages were other frequent errors. Overcrowding in pediatric wards is an obstacle to optimum patient care. Adequate number of nurses and support of pharmacists is essential for safe and optimum drug therapy. PMID- 1500132 TI - Prevalence of SSPE: a serological study. AB - The presence of measles antibodies in serum and cerebrospinal fluid (CSF) of 340 samples from children clinically suspected of subacute sclerosing panencephalitis (SSPE) were studied. One hundred and thirty eight (40%) of these children had SSPE based on the serological evidence. The mean age group of children affected was 8.2 years. The M:F ratio was 5:1. The titres of antibodies ranged from 1:2 to 1:32 in the CSF and from 1:16 to 1:512 in the serum. PMID- 1500133 TI - Frequency and significance of electrolyte abnormalities in pneumonia. AB - To determine the frequency of electrolyte disturbance in pneumonia, we studied 264 hospitalized children with pneumonia for serum sodium and potassium concentration, and plasma osmolality (Posm) on the day of admission. Urine osmalality (Uosm) and urine spot sodium concentration were measured in those who had a serum sodium less than or equal to 130 mEq/L. Hyponatremia was found in 27%, hypernatremia in 3.7%. Hypokalemia (serum potassium less than or equal to 3.5 mEq/L) in 19 and 2% had hyperkalemia (serum potassium greater than or equal to 6.5 mEq/L). Of all the hyponatremia, 68% were secondary to syndrome of inappropriate ADH secretion (SIADH) as suggested by a concomitant lowering of Posm less than or equal to 280 mosm/kg and increased urinary osmolality and sodium excretion. Hyponatremia was associated with 60% longer hospital stay, two fold increase in complications and the 3.5 times higher mortality compared to that of normonatremia. The above variables were affected further, if hypokalemia coexisted with hyponatremia. PMID- 1500134 TI - Evaluation of pediatric training of interns in a teaching hospital. AB - This study was undertaken in a teaching hospital with residency system to evaluate Pediatric teaching of interns admitted to MBBS course (using the questionnaire method) and to find out ways to improve the existing system. It was seen that the present system increased the Pediatric knowledge of interns significantly (p less than 0.001). The study highlights what the contents of the course should be from the learners' point of view, the hindrances to their learning and some suggestions to improve training in future. PMID- 1500135 TI - Treatment of neonatal gangrene: a new perspective. PMID- 1500136 TI - Perception towards breast feeding amongst working women teachers of a public school in Delhi. PMID- 1500137 TI - Multifocal osteomyelitis in a newborn. PMID- 1500138 TI - Inner canthal, outer canthal and inter pupillary distance in newborns. PMID- 1500139 TI - Disseminated tuberculosis and cardiac rhabdomyomata. PMID- 1500140 TI - Fatal rabies encephalomyelitis despite chick embryo vaccine prophylaxis. PMID- 1500141 TI - Successful treatment of hepatic hemangiomas with corticosteroids. PMID- 1500142 TI - Vertebral hemangioma with spinal cord compression: the role of pre-operative embolisation. PMID- 1500144 TI - Unusual presentation of poliomyelitis. PMID- 1500143 TI - Impact of universal immunization programme on the incidence of tetanus neonatorum. PMID- 1500145 TI - Acute paralytic poliomyelitis in rural Maharashtra. PMID- 1500146 TI - Iniencephalus clauses. PMID- 1500148 TI - Larsen syndrome with cardiac anomaly. PMID- 1500147 TI - Causes of early neonatal mortality. PMID- 1500149 TI - Spigelian hernia. PMID- 1500150 TI - Neonatal branding--towards branding eradication. PMID- 1500151 TI - Modified Rubner's test: diagnosis of secondary lactose intolerance diarrhea. PMID- 1500152 TI - Biliary atresia: need for an "Indian effort". PMID- 1500153 TI - Management of a baby of tuberculous mother. PMID- 1500154 TI - The vicious cycle of malnutrition-infection with special reference to diarrhea, measles and tuberculosis. PMID- 1500155 TI - Staphylococcal alpha toxin: a study with chronically instrumented awake sheep. AB - The in vivo responses to staphylococcal alpha toxin are reported for 15 chronically instrumented awake yearling sheep. The data obtained from a total of 30 experiments are grouped into four categories of response: no response, noted in seven experiments done on 5 sheep; pressor response, obtained seven times in 4 sheep; fluid and solute exchange, noted on six occasions in 3 sheep; and acute heart failure and death, which occurred in 10 of the 15 sheep. "No response" denoted no change in any of the measured outcome variables. The group of sheep labeled as showing "pressor response" responded to alpha toxin infusion with an increase in pulmonary artery pressure, unaccompanied by changes either in lung lymph flow or in lung mechanics. "Changes in lung fluid and solute exchange" involve increases in lung lymph flow. The harbinger of the last category, acute left heart failure leading to death, was a marked elevation in left atrial pressure. The threshold response dose in sheep is approximately 21 micrograms/kg. A very steep dose-response curve is observed, with only a narrow window of doses, 15 to 25 micrograms/kg, between the group showing no response and the group showing death from acute heart failure. The data obtained in these studies indicate that the lethal effects of alpha toxin in sheep include acute heart failure, which may be due to direct toxicity to heart muscle and/or the coronary vasculature endothelium. PMID- 1500156 TI - Resistance of severe combined immunodeficient mice to infection with Cryptosporidium parvum: the importance of intestinal microflora. AB - Cryptosporidium parvum is a protozoan parasite which colonizes intestinal epithelium, causing transient diarrheal illness in immunocompetent hosts and severe chronic disease in immunocompromised hosts. We examined the resistance of severe combined immunodeficient mice, either bearing intestinal flora or germfree, to intestinal infection with C. parvum. Infection was not readily detected in flora-bearing adult severe combined immunodeficient mice until 5 to 7 weeks following oral challenge with C. parvum. In contrast, germfree adult severe combined immunodeficient mice were heavily infected 3 weeks following challenge. These data support the hypothesis that resistance of adult mice to C. parvum infection does not require a specific immune response but can be mediated by nonspecific mechanisms associated with the presence of intestinal flora. PMID- 1500157 TI - Molecular population genetic evidence of horizontal spread of two alleles of the pyrogenic exotoxin C gene (speC) among pathogenic clones of Streptococcus pyogenes. AB - It has recently been demonstrated that the bacteriophage-borne gene (speC) encoding pyrogenic exotoxin C is harbored by phylogenetic lineages representing virtually the entire breadth of genomic differentiation present in the species Streptococcus pyogenes (J. M. Musser, A. R. Hauser, M. H. Kim, P. M. Schlievert, K. Nelson, and R. K. Selander, Proc. Natl. Acad. Sci. USA 88:2668-2672, 1991). To determine whether the speC genes occurring in association with divergent chromosomal genotypes (clones) are identical or represent a group of allelic variants, we sequenced speC from 23 S. pyogenes strains representing 15 clones identified by multilocus enzyme electrophoresis. Two alleles of speC are present in natural populations, and each allele occurs in clones that are well differentiated in overall chromosomal character; in one case, isolates of a single clone had different speC alleles. We interpret these patterns of toxin allele-clone distribution as evidence of occasional episodes of speC horizontal dissemination, presumably by bacteriophage-mediated gene transfer and recombination. PMID- 1500158 TI - Elimination of the vitamin B12 uptake or synthesis pathway does not diminish the virulence of Escherichia coli K1 or Salmonella typhimurium in three model systems. AB - The role of iron in infection is of great importance and is well understood. During infection, both the host and the pathogen go through many complicated changes to regulate iron levels. Iron and vitamin B12 share certain features. For example, Escherichia coli has similar transport systems for both nutrients, and binding proteins for both are located in gastric juice, liver, saliva, granulocytes, and milk. It is because of such parallels between iron and B12 that we have explored the role of B12 in virulence. A btuB::Tn10 insertion which disrupts the gene encoding the vitamin B12 receptor from E. coli K-12 was P1 transduced into a virulent E. coli K1 strain. In both an infant-rat model and a chicken embryo model, no difference in virulence between the wild-type and the mutant strains was found. Strains of Salmonella typhimurium with mutations in the cobalamin synthesis pathway (Cob) and in btuB were used in a mouse model of virulence. Mutation of the Cob locus or of btuB does not decrease virulence. Interestingly, the inability to synthesize vitamin B12 actually increases virulence compared with the wild type in the S. typhimurium model. This effect is independent of the B12 intake of the mice. PMID- 1500159 TI - Granulocyte-macrophage colony-stimulating factor increases the infectivity of Leishmania amazonensis by protecting promastigotes from heat-induced death. AB - We have studied the effect of granulocyte-macrophage colony-stimulating factor (GM-CSF) on the infectivity of promastigotes of Leishmania amazonensis, an obligate intramacrophage parasite. We measured the capacity of the promastigotes to infect macrophages after preincubation at different temperatures (28, 34, and 37 degrees C) with recombinant murine GM-CSF, as well as the effect of an anti murine GM-CSF antibody on the in vitro and in vivo infectivity of the parasite. GM-CSF increases the capacity of the promastigotes to infect cells when preincubated at 34 and 37 degrees C, whereas the anti-GM-CSF antibody exerts the opposite effect: it decreases the internalization rate and the progression of infection in macrophage cultures and slows the growth of the lesion in infected BALB/c mice. Neither of the described effects were observed when the in vitro and in vivo infections were made with amastigotes. Promastigotes die in a time dependent manner when incubated at temperatures higher than 28 degrees C in the absence of GM-CSF. They are protected from this heat-induced death by incubation with the recombinant hormone. Our interpretation of these data is that the increase in the infectivity of promastigotes when incubated with GM-CSF at the temperatures at which infection occurs (34 and 37 degrees C) is due to the larger number of surviving forms within the infecting population. The decrease in infectivity when they are incubated with the antibody is due to inhibition of the protection conferred by the GM-CSF produced by the macrophages during the in vitro and in vivo infections. PMID- 1500160 TI - Synthesis of a conjugate vaccine composed of pneumococcus type 14 capsular polysaccharide bound to pertussis toxin. AB - Type 14 is one of the common types isolated from patients of all ages with infections caused by Streptococcus pneumoniae. Its capsular polysaccharide (Pn14) is composed of a neutrally charged tetrasaccharide repeat unit. Pn14 does not elicit protective levels of antibodies in infants and children and is a less than optimal immunogen of the 23-valent vaccine for adults. Pertussis toxin (PT) is both a virulence factor and protective antigen of Bordetella pertussis: it is not soluble at neutral pH and forms insoluble complexes with acidic polysaccharides. Both Pn14 and PT are potential components of vaccines for infants and children. Accordingly, a synthetic scheme was devised to prepare a conjugate of Pn14 and PT. An adipic acid hydrazide derivative of Pn14 was bound to PT at pH 3.9 by carbodiimide-mediated condensation. The conjugation procedure inactivated the PT as assayed by CHO cell and histamine-sensitizing activity. The Pn14-PT conjugate elicited antibodies in mice to Pn14 at levels estimated to be protective in humans and elicited neutralizing antibodies to PT. We plan to evaluate Pn14-PT clinically. PMID- 1500161 TI - Enterotoxigenicity of Vibrio parahaemolyticus with and without genes encoding thermostable direct hemolysin. AB - Vibrio parahaemolyticus produces a thermostable direct hemolysin (TDH) that has been implicated in the pathogenesis of diarrheal disease caused by this organism. However, previous studies attempting to demonstrate the contribution of the hemolysin to virulence have been inconclusive. We investigated this putative virulence factor by using an isogenic TDH-negative (TDH-) strain constructed by specifically inactivating the two copies of the tdh gene encoding TDH. The enterotoxigenicities of the parent strain (AQ3815) and the mutant strain were tested by adding sterile culture supernatants to rabbit ileal tissue mounted in Ussing chambers. The culture filtrate of the parent strain produced a significant increase in short-circuit current (Isc), compared with the change induced by the TDH- mutant. The capacity of the culture filtrate of AQ3815 to increase the Isc was reduced by neutralization with anti-TDH serum, and the return of the cloned tdh gene to the TDH- mutant restored the ability to increase the Isc. These results were corroborated by rabbit ileal loop assays in which AQ3815 caused fluid accumulation but the TDH- mutant did not. No microscopic damage was seen in mucosal tissues exposed to the culture filtrate of either strain. These results indicate that TDH has an enterotoxigenic effect on rabbit small intestine and could be responsible for the watery diarrhea seen with V. parahaemolyticus. PMID- 1500162 TI - Heterogeneity of phenol oxidases in Cryptococcus neoformans. AB - Phenol oxidase enzymes, linked to virulence in Cryptococcus neoformans, were prepared from broken cells. More enzyme activity was found in the ultracentrifugation supernatant; less was found in the membrane fraction. Phenol oxidases were located in acrylamide gel electropherograms by activity staining with L-dihydroxyphenylalanine (DOPA). Mobility differences between soluble and solubilized membrane-bound phenol oxidases were not found. Comparison of enzymes produced at 25 and 37 degrees C revealed that the enzyme had lower activity and lower mobility at 37 degrees C. The mobility of 25 degrees C phenol oxidases from strains of C. neoformans var. gattii was lower than that of those from C. neoformans var. neoformans. Half of the phenol oxidase produced at 25 degrees C was bound by concanavalin A, while that produced at 37 degrees C was not bound. However, glucose starvation of cultures at 25 degrees C overnight resulted in increased amounts of enzyme which did not bind to concanavalin A. A given strain of C. neoformans produces different species of phenol oxidase under different culture conditions. PMID- 1500164 TI - Tumor necrosis factor and macrophage activation are important in clearance of Nocardia brasiliensis from the livers and spleens of mice. AB - The roles of tumor necrosis factor (TNF) and macrophage activation in clearance of Nocardia brasiliensis from BALB/c mouse livers and spleens were evaluated. TNF activity was detectable in sera from animals at all stages of infection. Treatment of infected mice with an antiserum against TNF significantly enhanced the experimental infection as judged by enumeration of CFU in the spleens and livers of infected mice. In another set of experiments, a population of activated macrophages from the peritoneal cavities of N. brasiliensis-infected mice was studied by using a cytostatic assay. The observed cytotoxic activity of these activated macrophages against L929 cells was mediated by TNF, since this activity was inhibited by anti-TNF antiserum treatment. The level of TNF activity generated in vitro in the presence of lipopolysaccharide (LPS) by peritoneal macrophages from infected mice was higher than that of adherent peritoneal cells obtained from normal mice after challenge with LPS. When the nocardiacidal activity of peritoneal cells from N. brasiliensis-infected mice was estimated in vitro, a significant decrease in the number of CFU recovered was observed. Moreover, nocardiacidal activity of peritoneal cells obtained from N. brasiliensis-infected mice previously treated with anti-TNF antiserum was significantly reduced compared with the activity of cells obtained from infected mice previously treated with normal rabbit serum and that of cells from uninfected mice. These data suggest a role for TNF in resistance to N. brasiliensis infection. PMID- 1500163 TI - Cryptdins: antimicrobial defensins of the murine small intestine. AB - Paneth cells are specialized small intestine epithelial cells that contain lysozyme, possess phagocytic properties, and secrete cytoplasmic granules into the intestinal crypt lumen after the entry of bacteria. Recent studies by Ouellette and associates (A. J. Ouellette, R. M. Greco, M. James, D. Frederick, J. Naftilan, and J. T. Fallon, J. Cell Biol. 108:1687-1695, 1989) indicated that murine Paneth cells produce prodefensin mRNA, but the properties of its peptide product were not reported. We purified two closely related defensins, cryptdin 1 and cryptdin 2, from a subcellular fraction of murine small intestine cells that was enriched in Paneth cells. Both peptides contained 35 amino acid residues, including the characteristic defensin "signature" of six invariantly conserved cysteines. Cryptdins 1 and 2 were approximately 90 to 95% homologous to each other and to the carboxy-terminal domain of the 93-amino-acid defensin precursor, cryptdin A, described by Ouellette and associates (Ouellette et al., J. Cell Biol. 108:1687-1695, 1989). Both cryptdins exerted bactericidal activity against Listeria monocytogenes EGD and Escherichia coli ML-35p in vitro. Their potency exceeded that of human neutrophil defensin HNP-1 but was considerably lower than that of NP-1, a defensin produced by rabbit neutrophils and alveolar macrophages. Both cryptdins killed mouse-avirulent Salmonella typhimurium 7953S (phoP) much more effectively than its phoP+, mouse-virulent, isogenic counterpart, S. typhimurium 14028S. Our data indicate that mouse intestinal prodefensins are processed into 35-amino-acid mature defensins (cryptdins) with broad-spectrum antimicrobial properties. The production of defensins and lysozyme by Paneth cells may enable them to protect the small intestine from bacterial overgrowth by autochthonous flora and from invasion by potential pathogens that cause infection via the peroral route, such as L. monocytogenes and Salmonella species. PMID- 1500165 TI - Protective effect of a T-cell-dependent immunosuppressive, B-cell-mitogenic protein (F3'EP-Si, or P90) produced by Streptococcus intermedius. AB - The role of a previously described bacterial protein (F3'EP-Si), now designated P90, in the survival of Streptococcus intermedius in the host was investigated, and the immunosuppressive and B-cell-mitogenic effects of this protein were further characterized. C57BL6 mice treated with P90 were about 50 times more susceptible to infection with this bacterium than untreated mice. One of seven splenocytes of C57BL/6 mice were activated by P90. Marked splenomegaly was observed in mice treated with P90, with increased numbers of splenic mononuclear cells and polyclonal immunoglobulin-secreting plaque-forming cells. Peak responses were seen on day 3 for immunoglobulin M (IgM) and on day 5 for IgG, with an isotypic pattern consisting predominantly of IgG2a and IgG2b. When mice were treated with P90 before being primed with sheep erythrocytes, polyclonal immunoglobulin synthesis was accompanied by an ephemeral stimulation of the specific immune response against sheep erythrocytes that was quickly replaced by a dramatic immunosuppression. In contrast, when mice were treated with P90 after being primed, the polyclonal activation was comparatively much less evident and there was no suppression of the specific immune response. Immunosuppression was considerably reduced in mice thymectomized as adults or depleted of CD8+ cells. Adoptive transfer experiments showed that B cells obtained from P90-treated mice were less able to respond to an antigenic challenge, even in the presence of normal T cells, and that T cells obtained from P90-treated mice could actively suppress the specific immune response of normal B cells. PMID- 1500166 TI - Lymphokine-activated killer cell regulation of T-cell-mediated immunity to Candida albicans. AB - Monocytes are important accessory cells in the activation of T cells for specific antigen recognition yet little is known of their regulation. We demonstrated here that interleukin-2 (IL-2)-induced human lymphokine-activated killer (LAK) cells can inhibit monocyte antigen presentation, depending on the state of differentiation of the monocytes. Adherent monocytes cultured for 4 days in medium or granulocyte-macrophage colony-stimulating factor (GM-CSF) were found to equally process and present intact Candida albicans to autologous Percoll gradient-isolated T cells, as measured by [3H]thymidine uptake. However, only the GM-CSF-cultured monocytes were functionally inhibited by autologous 4-day IL-2 induced LAK cells. Even soluble candidal cell wall mannoprotein antigens could not be presented by these monocytes after exposure to LAK cells. Pretreatment of these monocytes with LAK cells for 1 h, followed by subsequent removal of the nonadherent LAK cells, was sufficient to cause significant inhibition, with maximal inhibition observed after 4 h. Northern (RNA) blot analysis indicated that mRNA expression for IL-1 alpha and IL-1 beta in response to C. albicans stimulation was also down-regulated in GM-CSF-cultured monocytes exposed to LAK cells. Interestingly, freshly isolated, Percoll gradient-purified large granular lymphocytes did not suppress antigen presentation in GM-CSF-treated monocytes. Another important finding was the inability of LAK cells to suppress the ability of freshly isolated or gamma interferon-cultured monocytes, which are resistant to LAK cell-mediated lysis, to present antigen to T cells. In contrast, IL-3 was similar to GM-CSF in inducing LAK cell susceptibility in monocytes. Taken together, these results indicated that IL-2 can induce LAK cells to down-regulate antigen presentation function in a select set of monocytes that have been activated by colony-stimulating factor (GM-CSF and IL-3) but not by gamma interferon. LAK cells may therefore play an important role in regulation of monocytes and their function, depending on their differentiation state. PMID- 1500167 TI - Isolation of nonchemotactic mutants of Campylobacter jejuni and their colonization of the mouse intestinal tract. AB - Three nonchemotactic mutants (D54, Y14, and N74) of Campylobacter jejuni were isolated from wild-type strain FUM158432 by either the negative swarming or liquid gradient method with brucella broth as the attractive substance. Strains D54 and Y14 were isolated after mutagenesis with methyl methanesulfonate, and N74 was isolated from a nonmutagenized culture. These mutants all failed to swarm on a semisolid medium and did not show any chemotactic behavior in the hard-agar plus assay method for any of the chemicals which act as attractants for the wild type strain. They had intact flagella and were actively motile. Swimming behavior examined by a video tracking technique showed that the mutants swim only straight, without any tumbling. When suckling mice were challenged orally with approximately 10(5) CFU of these mutant strains, all of the mutants were cleared from the intestinal tract by 48 h. In contrast, the wild-type strain colonized the intestinal tracts of all mice challenged with 10(2) CFU. We concluded that chemotactic movement is important for colonization of the intestinal tract of suckling mice by C. jejuni. PMID- 1500168 TI - Isolation and molecular characterization of a novel albumin-binding protein from group G streptococci. AB - Many streptococcal strains are known to bind the two most abundant plasma proteins, namely, immunoglobulin G and albumin. Protein G isolated from group C and G streptococci has been demonstrated to have separate binding regions for each of these proteins. However, some group G streptococcal strains bind only serum albumin. This report describes the isolation of a 48-kDa albumin-binding protein from such a strain (DG12). The affinity constant of this protein for human serum albumin was determined to be 5 x 10(9) M-1, and the protein interacted strongly also with serum albumin from several other mammalian species. The gene encoding the albumin-binding protein was cloned and expressed in Escherichia coli. DNA sequence analysis of this gene revealed a unique NH2 terminal sequence and three types of repeats in the encoded protein. One of these repeated sequences has significant homology with the albumin-binding domains of protein G, and it was demonstrated that the albumin binding of the DG12 protein was localized within these domains. Another type of repeat is localized in the putative wall-spanning region of the molecule. This repeat sequence, which has the length of only 4 amino acids (LysProGluVal), is repeated 14 times. The relationship of the albumin-binding protein to other cell-wall-associated proteins of pathogenic streptococci is discussed. PMID- 1500169 TI - Host cell actin assembly is necessary and likely to provide the propulsive force for intracellular movement of Listeria monocytogenes. AB - Listeria monocytogenes is able to escape from the phagolysosome and grow within the host cell cytoplasm. By 3 h after initiation of infection, actin filaments begin to concentrate at one end of the bacterium. Polarization of F-actin is associated with intracellular bacterial movement, long projections of actin filaments forming directly behind the moving bacteria. New actin monomers are added to the region of the projection in proximity to the bacterium. The rate of new actin filament growth correlates closely with the speed of bacterial migration. This actin structure is anchored within the cytoplasm, serving as a fixed platform for directional expansion of the actin filament network. The actin projection progressively lengthens as the bacterium migrates. Cytochalasin blocks both elongation of the projection and bacterial movement but does not result in complete depolymerization of the bacterially induced actin structure, residual actin and alpha-actinin persisting in proximity to one end of the bacterium. Bacteria initially migrate within the cortical cytoplasm but later move to the peripheral membrane, where they form filopodiumlike structures which pivot and undulate in the extracellular medium. In the filopodia, bacteria are occasionally seen to abruptly change direction, turn 180 degrees, and move back into the medullary region of the host cell. All filopodium movement ceases once the bacterium containing the F-actin projection returns to the cortical cytoplasm. These results indicate that host cell actin polymerization is necessary for intracellular migration of listeriae and suggest that directional actin assembly may in fact generate the propulsive force for bacterial and filopodial movement. PMID- 1500170 TI - Molecular analysis of the serotyping antigens of Neisseria meningitidis. AB - Molecular approaches to the rapid analysis of the serotyping antigens of Neisseria meningitidis, the class 2 and 3 outer membrane proteins (OMPs), were developed, evaluated, and used to study 12 antigenic variants of these proteins. A primer set for the polymerase chain reaction (PCR) amplification of the genes encoding these antigens was devised. Low-stringency amplification of meningococcal chromosomal DNA with this primer set resulted in the amplification of two products from each strain, whereas at higher stringencies only one product was amplified in most strains. Southern hybridization techniques and restriction analyses were used to differentiate the PCR products amplified at high stringencies from strains expressing class 2 or class 3 OMPs; these PCR products were further characterized by the determination of their nucleotide sequences, confirming that they represented the amplified class 2 and class 3 OMP genes. Analyses of these and other nucleotide sequences enabled the construction of a phenogram illustrating the interrelationships between Neisseria OMP genes. The comparative analysis of deduced amino acid sequences revealed conserved and variable regions of the proteins; the latter probably correspond to surface loops on the protein and hence are potentially exposed to the immune system. Further analyses of the primary structures of these related porins from Neisseria species enabled construction of models of the secondary structure of these antigens and comparison of these models with those previously published. The methods reported in the present work are rapid reproducible procedures for the analysis of antigenic variants of these proteins. PMID- 1500171 TI - Borrelia burgdorferi stimulates release of interleukin-1 activity from bovine peripheral blood monocytes. AB - Infection with Borrelia burgdorferi is suspected to be a cause of lameness and arthritis in cattle. Interleukin-1 (IL-1) activity has been detected in joint fluids from human patients affected by various arthritides, including Lyme arthritis. In addition, human monocytes and murine macrophages have been reported to release IL-1 activity when incubated with B. burgdorferi in vitro. To address a possible mechanism by which B. burgdorferi might cause a bovine arthritic syndrome, we determined whether bovine peripheral blood monocytes released IL-1 activity when coincubated with B. burgdorferi in vitro. High-passage and low passage isolates of B. burgdorferi stimulated release of IL-1 activity from bovine monocytes. The amount of IL-1 activity released was dependent on the number of borreliae added to the monocyte cultures. In addition, live and heat killed B. burgdorferi cells stimulated release of similar amounts of IL-1. We also obtained no evidence that soluble components released from in vitro-cultured B. burgdorferi stimulated IL-1 release from bovine monocytes. A recombinant IL-1 receptor antagonist blocked the proliferative activity of monocyte-conditioned medium in a thymocyte costimulation assay, thus demonstrating that the costimulatory activity detected was due to IL-1. PMID- 1500172 TI - Contributions of complement and immunoglobulin to neutrophil-mediated killing of enterococci. AB - Enterococci have become a frequent causative agent in neonatal sepsis. The relative contributions of antibody and complement and their interactions in the neutrophil-mediated bacterial killing of 11 Enterococcus strains from neonates were investigated. Polymorphonuclear leukocytes (PMNL) from adult and term newborn infants were tested with normal human serum, adult hypogammaglobulinemic serum, and normal newborn serum in a neutrophil bactericidal assay. Neutrophil bactericidal activity for enterococci was not influenced by the serum source but was essentially ablated after heat inactivation of complement in all sera. No differences were observed in the killing capacity of healthy newborn versus adult PMNL regardless of serum source. Representative Enterococcus strains were then tested with agammaglobulinemic serum or C4-deficient serum, resulting in neutrophil bactericidal activities consistently exceeding 90%. A neutrophil bactericidal assay performed with normal rabbit serum and hyperimmune rabbit serum against enterococci showed that antibodies to enterococci enhanced neutrophil-mediated killing of this organism. Thus, neutrophil killing of enterococci appears to be mediated primarily by complement, with antibody playing a less essential but potentially important role. PMNL from adult and healthy term infants functioned with equal efficiency in the neutrophil killing of enterococci. PMID- 1500174 TI - Characteristics of Helicobacter pylori variants selected for urease deficiency. AB - The urease of Helicobacter pylori is suspected to play a role in the pathogenesis of gastritis. Although all clinical isolates of H. pylori are urease positive (U+), we have selected and characterized several spontaneously arising urease negative (U-) variants from wild-type strain 60190. Urease-negative variants were identified by growth in medium containing 60 mM urea and arose at a frequency of 10(-5) to 10(-6). The urease activity of the wild-type strain inhibited growth of this strain in the presence of 60 mM urea. U- variants retained the U- phenotype for more than 100 passages on medium with or without urea. The urease activities of the original U+ and derived U- cells were 9.55 to 16.7 and 0.01 to 0.17 U/mg of protein, respectively. Colonial growth and other biochemical characteristics were identical for the strains. U- variants showed three classes of whole-cell sodium dodecyl sulfate-polyacrylamide gel electrophoresis profiles: (i) identical to U+; (ii) change in the migration of the 61-kDa urease subunit; and (iii) lack of 61- and 30-kDa subunits. These differences were confirmed by immunoblotting and by protein separation using fast protein liquid chromatography. The U+ strain but not U- variants tolerated exposure to pH 4.0 for 60 min in the presence of urea. Supernatants of the U+ strain and U- variants contained vacuolating cytotoxin activity for HeLa cells in similar titers. By enzyme-linked immunosorbent assay, human serum samples recognized water extract from the U+ strain significantly better than extract from a U- variant lacking urease subunits. In conclusion, this study demonstrates that U- H. pylori variants may arise spontaneously, that urease activity enhances survival at acid pH, and that urease and cytotoxin activities are disparate phenotypes. PMID- 1500173 TI - Identification and purification of a second form of Cu/Zn superoxide dismutase from Schistosoma mansoni. AB - Our laboratories previously isolated a putative extracellular or membrane associated Cu/Zn superoxide dismutase (Cu/Zn-SOD) gene, designated a signal peptide-containing (SP) Cu/Zn-SOD, from Schistosoma mansoni. SOD activity was thus investigated throughout the life cycle of S. mansoni and found in all stages: eggs, miracidia, cercariae, schistosomula, lung-stage worms, and adult worms. The adult worms had the highest SOD activity (53 +/- 9 nitrite units), which was five times higher than that of eggs or miracidia and twice as high as that of 3-h-old mechanically transformed schistosomula. Cu/Zn-SOD constituted over 95% of the total SOD activity found in S. mansoni, compared with that of Mn SOD. Most of Cu/Zn-SOD specific activity was associated with a detergent extractable fraction of the parasite. Isoelectric focusing gel electrophoresis analysis revealed that there were four major pI variants of Cu/Zn-SOD present in the adult worms. Only two of these Cu/Zn-SOD pI variants were present in the 3-h old mechanically transformed schistosomula. Fast protein liquid chromatography gel filtration fractionation of adult parasite extract was carried out to correlate the SP Cu/Zn-SOD with the SOD activity by using anti-SP Cu/Zn-SOD monoclonal antibodies, which separated the immunoreactive gene product and the SOD activity into different fractions. Quantitative tissue fractionation also revealed a discordant distribution of the gene product compared with that of Cu/Zn-SOD activity. These results indicated the existence of another Cu/Zn-SOD(s) in the parasite. Purification of the Cu/Zn-SOD activity from the adult worms showed that it represented the two lower-pI variants found in both adult worms and 3-h-old schistosomula. Peptide sequence analysis of the purified Cu/Zn-SOD confirmed that there is a second form of Cu/Zn-SOD in the parasite. PMID- 1500175 TI - Macrophage response to bacteria: induction of marked secretory and cellular activities by lipoteichoic acids. AB - Lipoteichoic acids (LTAs) from various bacterial species, including Staphylococcus aureus, Streptococcus pyogenes, Streptococcus pneumoniae, Enterococcus faecalis, and Listeria monocytogenes, were examined for the ability to induce secretory and cellular responses in a pure population of bone marrow derived mononuclear phagocytes. Some of the highly purified LTAs, in particular LTAs from Bacillus subtilis, S. pyogenes, E. faecalis, and Enterococcus hirae, were able to affect each of the macrophage parameters measured, i.e., reductive capacity, secretion of tumor necrosis factor and nitrite, and tumoricidal activity. As after stimulation with whole organisms or other bacterial products, secretion of tumor necrosis factor induced by these LTAs reached its maximum within the first few hours of the interaction, while secretion of nitrite and tumoricidal activity required 24 to 36 h for full expression. Other purified LTAs, i.e., LTAs from Streptococcus sanguis, S. pneumoniae, and L. monocytogenes, as well as lipomannan from Micrococcus luteus affected only some of these parameters, while native LTA from S. aureus was inactive. There was no obvious correlation between biological activity and chain length, kind of glycosyl substituents, glycolipid structures, or fatty acid composition of LTAs. Deacylation of LTAs resulted in a complete loss of activity, and deacylated LTAs did not impair the activity of their acylated counterparts, suggesting that acyl chains may be essential for binding of LTA to the cell surface. The results demonstrate that some LTA species are potent inducers of macrophage secretory and cellular activities. PMID- 1500176 TI - Characteristics and cariogenicity of a fructanase-defective Streptococcus mutants strain. AB - Polymers of D-fructose produced by a variety of oral bacteria are believed to function as extracellular carbohydrate reserves. Degradation of these polysaccharides in plaque following exhaustion of dietary carbohydrates is thought to contribute to the extent and duration of the acid challenge to the tooth surface and thus to the initiation and progression of dental caries. Streptococcus mutans produces a fructanase, the product of the fruA gene, which is capable of degrading beta(2,6)- and beta(2,1)-linked fructans that are commonly synthesized by dental plaque microorganisms. To evaluate the role of the FruA protein in exopolysaccharide metabolism and to assess the contribution of this enzyme to the pathogenic potential of S. mutans, a fructanase-deficient strain of S. mutans was constructed. Inactivation of a cloned fruA gene was accomplished in Escherichia coli by using a mini-Mu dE transposon, and then an isogenic mutant of S. mutans UA159 was constructed by allelic exchange. Successful inactivation of fruA was confirmed through the use of biochemical assays, Western blotting (immunoblotting) with anti-recombinant FruA antisera, and Southern hybridization. The data indicated that FruA was the only fructan hydrolase produced by S. mutans UA159. Inactivation of fruA had no significant effects on glucosyltransferase or fructosyltransferase activity. In the rat caries model using animals fed a high-sucrose diet and ad libitum, there were no significant differences in the number or severity of smooth surface, sulcal, or root caries elicited by the fruA mutant and the wild-type organism. PMID- 1500177 TI - Experimental model of intracerebral infection with Cryptococcus neoformans: roles of phagocytes and opsonization. AB - A murine model of intracerebral (i.c.) infection with Cryptococcus neoformans in which naive mice receiving an i.c. fungal inoculation developed a severe disease has been established. The effect was strictly dependent on the number of microorganisms injected and evolved as lethal meningoencephalitis. Murine susceptibility to i.c. infection with C. neoformans was enhanced by treatment with chloroquine and colchicine, agents known to greatly affect the host phagocytic compartment. Furthermore, the life spans of both naive and drug treated mice were significantly augmented when opsonized fungi were injected. Therefore, phagocyte-mediated mechanisms are likely involved in local resistance to i.c. infection with C. neoformans. Further support for this conclusion was supplied by in vitro data showing that microglial cells were proficient anticryptococcal effectors, provided opsonized microorganisms were used. PMID- 1500178 TI - Group G streptococcal M protein exhibits structural features analogous to those of class I M protein of group A streptococci. AB - We have previously studied a collection of group G streptococcal strains isolated from bacteremic human infections and demonstrated that such strains resist phagocytosis by human polymorphonuclear leukocytes but are type specifically opsonized by homologous antiserum. We have now performed Southern hybridization analysis on genomic DNA from eight blood isolates. All eight isolates showed DNA homology to a group A emm24 gene probe. The M-protein gene of one of the isolates, strain 1750, has now been isolated. This gene (emmG1) encodes a polypeptide of 67 kDa (MG1) which is reactive with antibodies to the partially purified M protein of the parent strain. The predicted amino acid structure of MG1 demonstrates significant identity with the carboxy terminus (C, D, and anchor domains) of M6 and M24 but only limited identity with the amino terminus (variable portion) of these group A M proteins. Southern hybridization of genomic DNA of the eight group G blood isolates with an emmG1 gene probe indicated there were at least four emm alleles associated with these strains. These studies indicate that M proteins of group G streptococci, like those of group A, are genetically heterogeneous. Moreover, MG1 appears to conform to the recently proposed class I structure of M-protein molecules and thus shares certain distinct structural features with the M proteins of well-established rheumatogenic group A streptococcal serotypes. Further comparison of the structures of group G and group A M proteins of throat and skin isolates may cast light on those configurations of the M protein molecules which are and are not critical for the expression of rheumatogenicity. PMID- 1500179 TI - Comparison of the abilities of Mycobacterium avium and Mycobacterium intracellulare to infect and multiply in cultured human macrophages from normal and human immunodeficiency virus-infected subjects. AB - Patients with AIDS commonly develop disseminated infections with Mycobacterium avium (MA) but not its close relative, M. intracellulare (MI). In non-AIDS patients who have these infections, the two species are about equally distributed. The higher incidence of infection with MA than with MI in AIDS patients might be due to the selective susceptibility of these patients to MA. This possibility was tested by comparing the abilities of MA and MI to infect and replicate in cultured macrophages from normal subjects and from patients with AIDS-related complex or AIDS. The macrophages were cultured in medium supplemented with 1 or 5% normal or patient sera or with 1% defined serum substitute. Replication of MA (serovar 4) or MI (serovars 16 and 17) in the macrophages was measured by CFU counts made from lysed samples of the macrophages taken at 0,4, and 7 days after macrophage infection. MA and MI in infected normal macrophages which were cultured in normal serum replicated in these macrophages at similar rates. MA but not MI multiplied abnormally rapidly in patient macrophages cultured in either normal serum or patient serum. The accelerated growth of MA in patient macrophages was macrophage dependent, because patient sera did not change the rate of MA replication in culture medium lacking macrophages. However, patient sera did increase the permissiveness of normal macrophages to MA but not MI. These results suggest that a selective increased susceptibility to MA compared with a retained normal resistance to MI in human immunodeficiency virus-infected patients as they progress from AIDS-related complex to AIDS accounts for the higher prevalence of MA than MI infection in AIDS patients. The results also indicate that the mechanisms of native resistance in human macrophages to MA and MI are different. PMID- 1500180 TI - Immune specificity of murine T-cell lines to the major outer membrane protein of Chlamydia trachomatis. AB - The antigenically variant Chlamydia trachomatis major outer membrane protein (MOMP) is a target of antibody-mediated neutralization in vitro, and it is an important protein for designing a subunit vaccine. Knowledge of MOMP T-cell determinants will be essential to elicit rapid and strong immune responses following an encounter with infectious organisms. C. trachomatis-specific T-cell lines were derived from MOMP-immunized BALB/c mice and selected with intact organisms. We used these short-term T-cell lines to identify determinants of MOMP that could be recognized by T cells following processing of the intact organism. T-cell line proliferation in response to overlapping MOMP peptides showed that only a peptide encompassing the third variable segment (VS3) elicited a strong proliferative response. We further mapped determinants within the VS3 peptide and found that a sequence-conserved portion of the VS3 peptide elicited T-cell proliferation of T-cell lines from BALB/c mice. Thus, unlike the response to several MOMP peptides with unselected T cells, development of short-term T-cell lines with intact organisms restricted the repertoire of antigens capable of being recognized by MOMP-specific T cells. PMID- 1500181 TI - SCID mouse models of acute and relapsing chronic Toxoplasma gondii infections. AB - Lymphodeficient scid/scid (SCID) mice died from acute infection with a strain of Toxoplasma gondii that causes chronic infection with mild symptoms in immunocompetent non-SCID mice. However, most SCID mice reconstituted with spleen cells from immunocompetent mice 1 month prior to T. gondii infection survived in good health after a transient period during which they appeared ill. Unreconstituted SCID mice given sulfadiazine in their drinking water from day 10 of Toxoplasma infection onward survived the acute phase of infection and lived for many weeks without overt symptoms. Histological examination revealed Toxoplasma cysts in their brains. However, if sulfadiazine was withdrawn from the drinking water of these chronically infected SCID mice, the mice died within 1 week with large numbers of trophozoites throughout their brains. These findings establish SCID mice as a potentially useful resource with which to study various aspects of immunological control of T. gondii infection during either its acute or chronic phase. Furthermore, the ability to produce chronic infections with avirulent T. gondii in SCID mice and to cause acute relapsing infections at will suggests that SCID mice may be helpful in evaluating potential therapies for acute and chronic T. gondii infections in immunocompromised patients. PMID- 1500182 TI - In vivo induction of nitrite and nitrate by tumor necrosis factor, lymphotoxin, and interleukin-1: possible roles in malaria. AB - Tumor necrosis factor and related cytokines are thought to be implicated in cell mediated immunity and pathophysiology in malaria, but their mechanism of action has not been ascertained. Tumor necrosis factor has been reported to generate nitric oxide in vitro, so we have measured levels of this molecule and its products in the plasma of mice after they have received an injection of tumor necrosis factor, lymphotoxin, interleukin-1, gamma interferon, or interleukin-6, all of which have been reported to be increased in malaria. Total reactive nitrogen intermediate levels in plasma were assayed spectrophotometrically after exposing plasma to a copper-cadmium-zinc catalyst to convert nitrate to nitrite and then to Griess reagent. Tumor necrosis factor, lymphotoxin, and interleukin-1 all induced reactive nitrogen intermediates in vivo, with interleukin-1 showing the most activity. Tumor necrosis factor was then examined more closely. It induced more reactive nitrogen intermediates in malaria-infected mice than in normal mice, and appreciably more was in the form of nitrate than was in the form of nitrite. NG-methyl-L-arginine inhibited the in vivo generation of reactive nitrogen intermediates by tumor necrosis factor in a dose-dependent manner, implying that these molecules were arginine derived. These results are consistent with the possibility that tumor necrosis factor, lymphotoxin, and interleukin-1 may contribute to host pathology and parasite suppression through generation of nitric oxide. PMID- 1500184 TI - Genetic analysis of scrA and scrB from Streptococcus sobrinus 6715. AB - A DNA fragment containing scrA and scrB, which encode enzyme II of the phosphoenolpyruvate-dependent sucrose phosphotransferase system and sucrose-6 phosphate hydrolase, respectively, was isolated from a lambda gt10 genomic DNA library of Streptococcus sobrinus 6715. Both genes were located on a 4.2-kb DNA fragment which was maintained stably in Escherchia coli on low-copy-number vector pGB2. The recombinant E. coli clone expressed sucrose-hydrolytic activity on MacConkey agar base supplemented with raffinose or sucrose. Results from deletion analysis showed that the sucrose-metabolic activity was contained within a 3.5-kb region. The lactic acid bacterium Lactococcus lactis subsp. lactis LM0230, which is devoid of sucrose-metabolic activity, was used to study the enzyme activities encoded by scrA and scrB from S. sobrinus 6715. L. lactis transformants carrying the 4.2-kb S. sobrinus-derived DNA fragment on E. coli-Streptococcus shuttle vector pDL278 were able to grow at the expense of sucrose and exhibited enzyme II and sucrose-6-phosphate hydrolase activities. Results from hybridization studies and a comparison of the restriction endonuclease maps of the scrA- and scrB containing chromosomal regions from S. mutans GS5 and S. sobrinus 6715 suggested considerable divergence. PMID- 1500183 TI - Effects of cytokines, complement, and antibody on the neutrophil respiratory burst and phagocytic response to Plasmodium falciparum merozoites. AB - The interaction between Plasmodium falciparum merozoites and human neutrophils, as well as the role of cytokines, complement, and antimalarial antibody on this interaction, was examined in vitro by measuring luminol-dependent chemiluminescence and phagocytosis. Merozoites, in the presence of heat inactivated (56 degrees C/30 min) normal serum, had very little effect on the neutrophil chemiluminescence. This response was significantly enhanced by the addition of normal serum (containing normal complement activity). In the presence of serum or plasma containing anti-P. falciparum antibodies (IS) with no detectable complement activity, the merozoites induced a marked response characterized by an increase in initial peak rate of chemiluminescence and a sustained increased rate of chemiluminescence. However, this response was not further increased if IS containing complement activity was used. Pretreatment of neutrophils with either tumor necrosis factor alpha, lymphotoxin, or gamma interferon significantly increased the neutrophil response to IS-treated merozoites, reflected in an increased initial peak rate and sustained increased rate of chemiluminescence. The effects of cytokine treatment of neutrophils and IS opsonization of merozoites were synergistic. In association with the changes in the chemiluminescence responses, IS was shown to promote phagocytosis of merozoites by neutrophils, and this event was further increased by treating neutrophils with the cytokines. The results emphasize the importance of antibody and cytokines in neutrophil-mediated damage of P. falciparum merozoites. PMID- 1500185 TI - Immune cell lethality induced by streptococcal pyrogenic exotoxin A and endotoxin. AB - Streptococcal pyrogenic exotoxin (SPE) A has many effects on the immune system, including immunolethality, which is characterized by a significant decrease in circulating immune cells as well as depletion of the spleen and lymph nodes prior to death of experimental animals. In this report, characterization of the mechanism of immunolethality has been undertaken. Synergistic induction of immunolethality was observed in vitro when human lymphocytes were treated with both SPE A and lipopolysaccharide (LPS). The same effect was demonstrated in the absence of a mitogenic response with the murine T-cell receptor, as well as in the absence of antigen-presenting cells and their secreted cytokines. The addition of antigen-presenting cells did not significantly affect lethality. SPE A directly interacted with LPS through interaction with ketodeoxyoctonate as demonstrated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and iodinated exotoxin overlays. This interaction was demonstrated to be important for immunolethality, since simultaneous addition of SPE A and LPS was required, whereas sequential addition of SPE A and LPS did not result in lethality. LPS appeared to be acting, in part, to enhance the cell-binding ability of SPE A, since SPE A could only be detected in A.E7 cell membrane preparations after simultaneous incubation with SPE A and LPS. PMID- 1500186 TI - Effects of gamma interferon on release of tumor necrosis factor alpha from lipopolysaccharide-tolerant human monocyte-derived macrophages. AB - After an initial stimulation of human monocyte-derived macrophages with bacterial lipopolysaccharide (LPS), which produces substantial release of tumor necrosis factor-alpha (TNF-alpha), a subsequent exposure to LPS results in about an order of-magnitude reduction in the levels of TNF-alpha released. We have shown that macrophages which have been stimulated with LPS and then maintained in culture without LPS for as long as 2 weeks do not regain their original capacity to secrete TNF-alpha upon a second LPS challenge. After 2 to 4 days in adherent culture, monocyte-derived macrophages which were not pretreated with LPS also experience a measurable decline in their capacity to release TNF-alpha in response to an initial LPS stimulation. When compared with these previously nonstimulated cells, however, the levels of TNF-alpha released by LPS-pretreated cells in response to a second LPS challenge decline by over 90% after 8 to 9 days in culture. Unstimulated cells spontaneously release barely detectable levels of TNF-alpha. In contrast to the release of TNF-alpha, unstimulated cells release significant levels of prostaglandin E2 continuously over time, and these levels are variably increased by no more than a factor of two in response to a single LPS stimulation. Prostaglandin E2 levels released by LPS-pretreated cells in response to a second LPS stimulation are much closer to the levels released by unstimulated cells. We have also demonstrated that gamma interferon (IFN-gamma) enhances TNF-alpha release from LPS-stimulated macrophages but not from phorbol myristate acetate-stimulated cells. Addition of IFN-gamma to macrophages either during the initial stimulation or during a second stimulation with LPS enhances levels of TNF-alpha released after the second LPS challenge. The greatest enhancement is observed when IFN-gamma is added during both exposures to LPS, but addition of IFN-gamma during only the initial LPS stimulation still results in marked enhancement of TNF-alpha release in response to a second stimulation with LPS 24 h later. If an interval of 2 days of culture in medium alone separates the first and second 24-h LPS stimulations, IFN-gamma enhances TNF-alpha release only when it is included during the second LPS exposure, indicating that, unlike the persistence of endotoxin tolerance, enhancement of TNF-alpha release by IFN-gamma is transient. PMID- 1500187 TI - Recombinant Salmonella typhimurium strains that invade nonphagocytic cells are resistant to recognition by antigen-specific cytotoxic T lymphocytes. AB - To address the question of whether Salmonella-infected nonphagocytic cells could serve as target cells for recognition by antigen-specific, major histocompatibility complex class I-restricted cytotoxic T lymphocytes (CTL), four recombinant Salmonella typhimurium constructs that expressed full-length, or fragments of, influenza A virus nucleoprotein (NP) were made. The bacteria were shown to infect Chinese hamster ovary (CHO) cells. Appropriate major histocompatibility complex restriction molecules, HLA-B27 and H-2 Db, were transfected into CHO cells, which were then infected with recombinant S. typhimurium and used as targets for NP-specific CTL. The cells in which NP was expressed by intracellularly replicating bacteria were not lysed by NP-specific CTL, although they were killed when appropriate influenza A virus or peptides were used. Thus, S.typhimurium bacteria within nonphagocytic cells were resistant to CTL recognition. In contrast to these results, mice infected with recombinant S.typhimurium that expressed fragments of NP in the periplasm were primed for NP specific CTL responses. The results indicate that CTL responses specific to Salmonella antigens can be generated, but the bacteria may be safe from the CTL attack once they have entered the nonphagocytic cells. PMID- 1500188 TI - Role of endotoxin in alterations of hepatic drug metabolism by diphtheria and tetanus toxoids and pertussis vaccine adsorbed. AB - Administration of diphtheria and tetanus toxoids and pertussis vaccine adsorbed (DTP vaccine) or endotoxin (LPS) resulted in marked alterations in hepatic drug metabolizing enzymes in endotoxin-responsive (R) and non-endotoxin-responsive (NR) mice. A single human dose (0.5 ml) of DTP vaccine increased hexobarbital induced sleep times to 1.6- to 1.8-fold above those of controls in both strains of mice. This effect persisted for 7 days. In contrast, Bordetella pertussis LPS treated mice showed an increase at 1 day (3.0-fold for R mice and 1.5-fold for NR mice), which returned to control levels by day 7. Furthermore, cytochrome P-450 levels were decreased 30 to 40% 24 h after DTP vaccine administration in both R and NR mice, while after LPS administration they were decreased 30% in R mice and less than 10% in NR mice. Both spleen and liver weights of R and NR mice were increased 7 to 14 days following DTP vaccine administration. However, LPS treatment had no apparent effect on liver weights, and spleen weights of R mice were elevated from days 3 to 7. Histopathologic tissue examination showed random, multifocal inflammation with hepatocyte necrosis after DTP vaccine administration to both R and NR mice and an absence of lesions in LPS-treated mice. Premixing LPS with polymyxin eliminated the increased sleep times, but premixing DTP vaccine with polymyxin did not affect the increased sleep times. Levels of tumor necrosis factor and interleukin-6 in plasma of R mice were markedly increased after DTP and LPS treatment, while NR mice had reduced increases. These results suggest that LPS contributes to the alterations in R and NR mice seen within the first 24 h of vaccine administration but that it is not likely to contribute to the effects observed at later time points. PMID- 1500189 TI - Chelating agents inhibit activity and prevent expression of streptococcal glucan binding lectins. AB - Several of the cariogenic mutans streptococci produce cell wall-associated glucan binding lectins (GBLs). The lectins bind alpha-1,6-linked glucans and have no affinity for other polysaccharides or anomeric linkages. When citrate or lactate was included in the growth medium, expression of the activities of the GBLs of Streptococcus cricetus and S. sobrinus was prevented. Furthermore, chelating agents, including citrate, lactate, EDTA, and acetylacetone, were able to reversibly inhibit glucan-induced aggregation of GBL+ streptococci. In addition, the chelating agents prevented sucrose-dependent streptococcal adhesion to glass surfaces and dispersed preformed adherent masses of the streptococci. Neither citrate nor other chelating agents modified the activities of glucosyltransferases. Expression of the lectin could only be achieved by the addition of manganous ion to the growth medium. Chloramphenicol and other metabolic inhibitors prevented synthesis of GBL in cells obtained from manganese deficient medium and shifted to manganous ion-sufficient medium. The GBL may be a manganoprotein, the manganese of which may be perturbed, but not removed, by chelating agents. During synthesis of the GBL, manganous ion may be required in order for the protein to achieve an active conformation. Citrate or other chelating agents may have promise as anticaries agents. PMID- 1500190 TI - Coxiella burnetii superoxide dismutase gene: cloning, sequencing, and expression in Escherichia coli. AB - A superoxide dismutase (SOD) gene from the obligate intracellular bacterium Coxiella burnetii has been cloned, and its DNA sequence has been determined and expressed in Escherichia coli. The gene was identified on pSJR50, a pHC79-derived genomic clone, by using the polymerase chain reaction with degenerate oligonucleotide primers corresponding to conserved regions of known SODs. Sequences resembling conventional E. coli ribosomal and RNA polymerase-binding sites preceded the C. burnetii 579-bp SOD open reading frame. An E. coli SOD deficient double mutant (sodA sodB) that carried pSJR50 had growth and survival responses similar to those of the wild type when the transformant was challenged with 0.05 mM paraquat and 5 mM hydrogen peroxide, respectively. These observations indicated that the C. burnetii gene was functionally expressed in E. coli. Staining of native polyacrylamide gels for SOD activity demonstrated that pSJR50 insert DNA codes for an SOD that comigrates with an SOD found in C. burnetii cell lysates. The enzyme was inactivated by 5 mM hydrogen peroxide, which is indicative of an iron-containing SOD. Additionally, the predicted amino acid sequence was significantly more homologous to known iron-containing SODs than to manganese-containing SODs. Isolation of the C. burnetii SOD gene may provide an opportunity to examine its role in the intracellular survival of this rickettsia. PMID- 1500192 TI - Expression of the eukaryotic Trypanosoma cruzi CRA gene in Yersinia enterocolitica and induction of an immune response against CRA in mice. AB - The 70-kb plasmid pYV of Yersinia enterocolitica directs the secretion of a set of proteins, called Yops, that are produced during infection of humans and animals. Trypanosoma cruzi, the agent of American trypanosomiasis, synthesizes a cytoplasmic protein termed CRA that is considered to be T. cruzi specific. To produce CRA in Y. enterocolitica, we constructed a hybrid yopE-CRA gene that we integrated into plasmid pYV by homologous recombination. Recombinant Y. enterocolitica produced a chimeric Yop-CRA protein that was secreted in large amounts in the surrounding medium. This protein reacted with sera directed against either CRA or YopE. To test the ability of the recombinant strain to induce an immune response against CRA, we inoculated C57BL/6J mice by gastric intubation with live recombinant bacteria. A clear antibody response directed against CRA was detected in the mouse serum. The CRA-presenting Y. enterocolitica strain also carried a bioluminescence detection marker, which allowed us to monitor colonization of the intestinal lumen of infected mice. No significant differences were observed between the infectivity of the CRA antigen-producing and -nonproducing Y. enterocolitica strains, despite the fact that one of them no longer produced YopE. PMID- 1500191 TI - Immune response to outer membrane antigens of Moraxella catarrhalis in children with otitis media. AB - The systemic and local antibody responses to homologous strains of Moraxella catarrhalis were investigated in 14 children with otitis media. A total of 8 children (57%) demonstrated a rise in serum antibody of the immunoglobulin G (IgG) (5 of 14), IgM (5 of 14), or IgA (6 of 14) classes of immunoglobulin to outer membrane antigens. Local antibody consisted of IgG (100%), IgM (29%), and IgA (71%). The IgG and IgA specific antibody present in middle-ear effusions appeared to represent local production rather than passive diffusion from the systemic circulation. These data suggest that young children develop an antibody response to M. catarrhalis in the middle ear during otitis media but fail to develop systemic antibody in a uniform manner. PMID- 1500193 TI - Evidence that autologous idiotypic regulation of anti-arginine-glycine-aspartic acid autoantibodies may influence development and progression of syphilitic lesions in infected rabbits. AB - The 83-kDa receptor protein of Treponema pallidum (TpN83) recognizes and binds fibronectin (Fn) at the amino acid sequence RGD site. By using experimentally infected animals, we have demonstrated that immunoglobulin G antibodies to this antigen and autoantibodies to the RGD site of Fn are putative components of immune complexes. This, and other findings, led us to initially hypothesize that anti-idiotypes (anti-Id) of an anti-TpN83 response are autoantibodies to RGD. Alternatively, we reasoned that if anti-Fn autoantibodies played a role in the pathogenesis of syphilis, then down-regulation of such a response by the Id network might directly affect progression of the disease. To test the hypothesis, rabbits were immunized with either affinity-purified TpN83 antigen or the synthetic Fn-7 peptide, KYGRGDS, and subsequently challenged with T. pallidum. Compared with results obtained with unimmunized, control rabbits, accelerated lesion development was noted in the rabbits immunized with TpN83. Pronounced, though unexpected, differences with respect to lesion development and progression were noted in the animals immunized with Fn-7 and then challenged intravenously; a minimal number of lesions appeared with a delayed onset. These lesions, like the localized chancres seen following intradermal challenge, were smaller and minimally ulcerated, and they healed rapidly. The Fn-7-immunized rabbits all differed from the controls in that anti-Id to anti-RGD F(ab')2 were demonstrable within 4 weeks following infection; decreases in anti-Fn autoantibody levels were associated with concomitant increases in anti-Id levels. Immunoglobulin Gs (anti Id) from these animals following elution from anti-RGD F(ab')2 immunoaffinity columns also reacted with affinity-purified TpN83 antigen in immunoassays. These results suggest that down-regulation of autoreactive clones by manipulation of the idiotypic network in experimental syphilis warrants further investigation. PMID- 1500194 TI - Iron acquisition and hemolysin production by Campylobacter jejuni. AB - Campylobacter jejuni strains were tested for their ability to acquire iron from various iron sources present in humans. Hemin, hemoglobin, hemin-hemopexin, and hemoglobin-haptoglobin stimulated the growth of C. jejuni strains in low-iron medium. Transferrin, lactoferrin, and ferritin were unable to provide iron to the strains tested. Derivatives of the naturally transformable C. jejuni strain 81 176 were isolated on the basis of their inability to use hemin as an iron source. These mutants were also unable to use hemoglobin, hemin-hemopexin, or hemoglobin haptoglobin as iron sources. Some mutants lacked a 71,000-Da iron-regulated outer membrane protein, while others appeared to retain all of their outer membrane proteins. Growth curves and a recombination experiment that exploited natural transformation were used to further characterize the mutants. A hemolytic activity was shown to be produced by several C. jejuni strains, but it did not appear to be iron regulated. PMID- 1500195 TI - Influence of saliva on aggregation and adherence of Streptococcus gordonii HG 222. AB - The influence of saliva on the aggregation and adherence of Streptococcus gordonii HG 222 was studied. The aggregation was measured spectrophotometrically, and the adherence of S. gordonii to microtiter plate wells was measured in an enzyme-linked immunosorbent assay system. The aggregation of HG 222 was induced primarily by mucous saliva, whereas the adherence of HG 222 to microtiter plates was mediated by both mucous and serous saliva. Fractions of submandibular saliva, obtained by gel filtration and containing low-molecular-weight mucins (MG-2), induced both bacterial aggregation and adherence. Purified MG-2 induced aggregation and promoted adherence, whereas high-molecular-weight mucins (MG-1) did not. After incubating clarified human whole saliva with HG 222, only MG-2, and not MG-1, was bound by the bacteria. Proline-rich proteins (PRPs) and proline rich glycoprotein (PRG) promoted the adherence of HG 222. These proteins in solution bound to HG 222 but did not induce aggregation of the bacterial cells. PRPs and PRG in solution were not able to inhibit adherence to microtiter plate wells coated with the same components. Purified alpha-amylase hardly promoted adherence to microtiter plates but, in the soluble state, readily bound to HG 222. In conclusion, these results indicate that the aggregation of S. gordonii HG 222 is mediated primarily by MG-2. These mucins also promote adherence. Several other salivary components, such as PRPs and PRG, are also involved in the adherence of HG 222. PMID- 1500196 TI - Toxicity and immunogenicity of Neisseria meningitidis lipopolysaccharide incorporated into liposomes. AB - To obtain nontoxic and highly immunogenic lipopolysaccharide (LPS) for immunization, we incorporated Neisseria meningitidis LPS into liposomes. Native LPS and its salts were incorporated by the method of dehydration-rehydration of vesicles or prolonged cosonication. The most complete incorporation of LPS into liposomes and a decrease in toxicity were achieved by the method of dehydration rehydration of vesicles. Three forms of LPS (H+ form, Mg2+ salt, and triethanolamine salt) showed different solubilities in water, the acidic form of LPS, with the most pronounced hydrophobic properties, being capable of practically complete association with liposomal membranes. An evaluation of the activity of liposomal LPS in vitro (by the Limulus amoebocyte test) and in vivo (by monitoring the pyrogenic reaction in rabbits) revealed a decrease in endotoxin activity of up to 1,000-fold. In addition, the pyrogenic activity of liposomal LPS was comparable to that of a meningococcal polysaccharide vaccine. Liposomes had a pronounced adjuvant effect on the immune response to LPS. Thus, the level of anti-LPS plaque-forming cells in the spleens of mice immunized with liposomal LPS was 1 order of magnitude higher and could be observed for a longer time (until day 21, i.e., the term of observation) than in mice immunized with free LPS. The same regularity was revealed in a study done with an enzyme-linked immunosorbent assay. This study also established that antibodies induced by immunization belonged to the immunoglobulin M and G classes, which are capable of prolonged circulation. Moreover, liposomal LPS induced a pronounced immune response in CBA/N mice (defective in B lymphocytes of the LyB-5+ subpopulation). The latter results indicate that the immunogenic action of liposomal LPS occurs at an early age. PMID- 1500197 TI - Interleukin-2 receptors in experimental Chagas' disease. AB - Mammals infected with the protozoan parasite Trypanosoma cruzi develop suppressed cellular and humoral immune responses. This immunosuppression has been correlated with reduced T-cell responses involving deficient interleukin-2 (IL-2) production and is apparently mediated primarily by suppressor macrophages. Various forms of immunosuppression in other systems have been associated with increased levels of soluble IL-2 receptors (sIL-2R), and in the present study levels of sIL-2R in the sera of T. cruzi-infected mice during the course of infection were examined in enzyme-linked immunosorbent assays. It was found that serum levels of sIL-2R were elevated only during the third week of acute infection, a time of intense immunosuppression. In addition, IL-2R on the surface of T cells were examined by flow cytometric analyses to determine whether there is an alteration in the number of IL-2R-positive cells and whether there is a change in expression of these receptors as infection progresses. The results revealed no significant change in the percentage of cells expressing IL-2R, nor did T cells become suppressed in their ability to express IL-2R in response to concanavalin A during the course of infection. PMID- 1500199 TI - Effect of pyocyanine, a pigment of Pseudomonas aeruginosa, on production of reactive nitrogen intermediates by murine alveolar macrophages. AB - In this study we investigated the effect of pyocyanine, a pigment produced by Pseudomonas aeruginosa, on production of reactive nitrogen intermediates by macrophages. We found that addition of pyocyanine to cultures of murine alveolar macrophages inhibited the capacity of these cells to produce reactive nitrogen intermediates (measured as nitrite) in a dose-dependent manner without altering cell viability, cytokine-induced Ia expression, or production of tumor necrosis factor. PMID- 1500200 TI - Safety and immunogenicity of a booster dose of Vibrio cholerae CVD 103-HgR live oral cholera vaccine in Swiss adults. AB - Adult volunteers received a booster dose (4 x 10(8) CFU) of attenuated Vibrio cholerae CVD 103-HgR oral vaccine 15 or 24 months after primary immunization. The immune response was modest, presumably due to rapid clearance of the vaccine strain by a primed immune system. PMID- 1500198 TI - The integrin-binding domain of invasin is sufficient to allow bacterial entry into mammalian cells. AB - Yersinia pseudotuberculosis is able to enter normally nonphagocytic host cells by multiple pathways, the most efficient of which is mediated by invasin, a 986 amino-acid bacterial outer membrane protein. It has previously been shown that the C-terminal 192 amino acids of invasin are sufficient to bind mammalian cells. To determine if additional regions of the invasin protein are necessary to promote entry, we developed a novel assay that tests the ability of various invasin derivatives to confer on Staphylococcus aureus the ability to enter animal cells. We determined that the 192-amino-acid cell-binding region of invasin, when used to coat the bacterial cell surface, was also sufficient to promote cellular penetration. These results suggest that the simple binding of invasin to its receptors is sufficient to mediate entry and that the bacterium plays a largely passive role in the entry process. PMID- 1500201 TI - Identification of an acute-phase reactant in murine infections with Trypanosoma brucei. AB - A 42-kDa protein appeared at a much higher concentration in plasma from Trypanosoma brucei-resistant (C57BL/6) mice after infection than in plasma from trypanosome-susceptible (C3H/He) mice. This protein was purified by sequential steps of gel filtration, protein A-Sepharose affinity chromatography, isoelectric focusing, and ammonium sulfate precipitation. The purified protein was identified as a subunit of the acute-phase reactant haptoglobin. Causes of elevated plasma haptoglobin and its implications for resistance to trypanosomiasis are discussed. PMID- 1500202 TI - Results of the third immunology of leprosy/immunology of tuberculosis antimycobacterial monoclonal antibody workshop. AB - An international workshop was sponsored by the World Health organization to screen new antimycobacterial monoclonal antibodies and to identify antibodies which could be recommended as standard reagents giving consistent results under differing assay conditions. Fifty-eight antibodies were submitted to the workshop by eight independent laboratories. Nineteen of the antibodies recognized antigens distinct from those identified in earlier workshops, defining at least 10 new protein antigens. Monoclonal antibodies characterized in the workshop provide a set of convenient reagents for further characterization of mycobacterial antigens. PMID- 1500203 TI - Induction of circulating group II phospholipase A2 expression in adults with malaria. AB - High levels of interleukin 1 and tumor necrosis factor are found in both cases of malaria and cases of septic shock. Since both interleukin 1 and tumor necrosis factor induce expression of the proinflammatory enzyme phospholipase A2 (PLA2), we examined serum PLA2 levels in 14 adults with malaria. Mean serum PLA2 activity was elevated 40-fold above normal (P less than 0.001). Serum PLA2 activity correlated with PLA2 immunoreactivity (r = 0.987; P less than 0.001) by an enzyme linked immunosorbent assay specific for human group II PLA2, showing that serum PLA2 in cases of malaria is host derived. This article describes the novel finding of elevated PLA2 levels in cases of malaria, further strengthening the notion that mediators of the host response in cases of malaria are similar to those in cases of septic shock. PMID- 1500204 TI - In vivo complement activation and binding of C3 to encapsulated Cryptococcus neoformans. AB - Tissues from mice infected with Cryptococcus neoformans were examined by immunofluorescence to determine the extent of deposition of complement component C3 on encapsulated cryptococci. The relative percentages of cryptococci in each tissue having readily visible C3 were greatest for liver and lung tissues, with the kidney tissue having the next highest percentage and the spleen having the lowest percentage. Binding of C3 fragments to cryptococci in brain tissue was essentially absent. PMID- 1500205 TI - Inefficiency of in vivo candidacidal mechanisms in experimental subcutaneous infections with Candida albicans in mice. AB - A murine model of subcutaneous Candida albicans infections was used to evaluate host defenses against inocula of from 10(1) to 10(8) yeast cells. In these experiments, small inocula did not produce abscesses that drained to the skin surface, whereas larger ones did. Also, small numbers of organisms often remained at the infected sites for up to 21 days after inoculation with either small or large numbers of organisms. The data from these studies suggest that the in vivo candidacidal mechanisms in these infections are relatively inefficient and that they therefore may require some additional mechanism to control proliferation of the remaining organisms. PMID- 1500206 TI - Phosphatidylserine found in intestinal mucus serves as a sole source of carbon and nitrogen for salmonellae and Escherichia coli. AB - Salmonella choleraesuis (a pig pathogen), Salmonella typhimurium (a virulent strain in mice), and three strains of Escherichia coli (including a human enterohemorrhagic strain, a human urinary tract isolate, and a human fecal isolate) grew as well in vitro utilizing the lipids derived from mouse cecal mucus as the sole source of carbon and nitrogen as they did in mouse crude cecal mucus. Further analysis of the total lipid extracts of mucus dialysates showed that the acidic lipid fraction supported growth nearly as well as the total lipid fraction. Interestingly, among the many purified acidic lipids from mucus which were tested and analyzed, including several phospholipids, only phosphatidylserine was found to support the growth of all of these enteric bacteria, including Salmonella milwaukee, a human pathogen. The possible role of growth on pure phosphatidylserine in the pathogenesis of salmonellae is discussed. PMID- 1500207 TI - A conjugated synthetic peptide corresponding to the C-terminal region of Clostridium perfringens type A enterotoxin elicits an enterotoxin-neutralizing antibody response in mice. AB - A synthetic peptide homolog corresponding to the C-terminal 30 amino acids of Clostridium perfringens type A enterotoxin (CPE) was conjugated to a thyroglobulin carrier and used to immunize mice. Conjugate-immunized mice produced antibodies which neutralized native CPE cytotoxicity, at least in part, by blocking enterotoxin binding. This peptide may be useful for the development of a vaccine to protect against CPE-mediated disease. PMID- 1500208 TI - Secondary caries. AB - This paper reviews secondary caries which is the major reason for failure of restorations and therefore worthy of attention if operative dentistry is to be cost effective. The basic premise of the review is that the secondary caries process is difficult to diagnose and cannot be permanently treated away by operative management. Preventive therapy, dependent on the patients' self-care, is essential. However, the quality of the restorative material and the skill with which it is handled are also relevant to the prevention of further failure. PMID- 1500209 TI - Types of resin-based inlay materials and their properties. AB - The composition of 'chairside' resin-based inlay materials is similar to that of direct resin-based filling materials. The handling and curing procedures vary for the different inlay materials. Some systems involve precuring inside the oral cavity and a final cure at elevated temperature outside the oral cavity. Others are only cured extra-orally. The advantage of the inlay technique is that polymerisation shrinkage of the composite occurs before bonding to tooth structure. After cementation, therefore, the inlay gives good marginal adaptation in occlusal restorations. Some of the curing procedures for inlays give good conversion. The systems with good conversion also show better mechanical properties than the equivalent resin-based material cured according to the direct filling technique. PMID- 1500210 TI - Luting agents for ceramic and polymeric inlays and onlays. AB - The requirements for luting agents for ceramic and polymeric inlays and onlays are reviewed and discussed. The current overriding consideration seems to be the chemical adhesion of the restoration to tooth substance and this is challenged as being an overambitious goal. The systems in use are principally the dual cure resin based cements and these have some disadvantages such as restricted and slow cure, chemical degradation and, most importantly, shrinkage on setting. This shrinkage, when the material is used in conjunction with a dentine bonding agent, is almost certain to guarantee the rupture of any bond formed. It is suggested that the objectives of the luting agent should be rethought with reference back to the well established principles of cast metal restorations. PMID- 1500211 TI - The WHO Oral Health goals for the year 2000 in South Africa. AB - This paper outlines a policy to attain the WHO Oral Health goals for the year 2000 by the implementation of primary and secondary prevention. The Republic of South Africa (RSA) with its complex political and social formation and an interesting mix of 1st and 3rd world populations provides the space for challenging and innovative approaches. PMID- 1500212 TI - Dental development in the midwest of America. AB - During the early nineteenth century, dentistry was just beginning its existence as a profession and emerging from a trade into a profession in the United States. Dental schools were being established to replace preceptorships as a means of training and members of the profession became aware of the need to draw up laws for the regulation of the professions. The Midwest of the United States participated in these changes and many of the dental practitioners of the Midwest started the reforms that ultimately led to the establishment of dentistry as a profession. Some of these originators and their contributions are reviewed. PMID- 1500213 TI - Changing scene in cariology and operative dentistry. PMID- 1500214 TI - Protective gloves. AB - The worldwide emergence of acquired immune deficiency syndrome (AIDS) has led to the wide use and acceptance of gloves as a measure of protection against infection in dental practice. Problems caused by the frequent use of gloves are already known from experiences in the surgical sector and have taken on a new urgency: these include impermeability, the difficulties of disinfection, and adverse skin reactions. In addition, there are specific dental questions such as the interference of gloves with electrical sensitivity tests and also with the taking of impressions. This paper discusses topical aspects of glove use and possible solutions to current problems. PMID- 1500215 TI - Secretion of autocrine growth-promoting activity by renal-carcinoma cells treated with 5-fluorouracil. AB - A study was made of the auto-proliferative activity of human renal-carcinoma cells in the supernatant from a carcinoma-cell culture in serum-free medium to which an anticancer agent had been added (5-FU). The human renal-cancer cells used in this study were of 3 strains: ACHN, VMRC-RCW and NT. When each line was cultured in medium containing no 5-FU, the supernatant showed almost no activity for stimulating DNA synthesis. However, when the line was cultured in the presence of 5-FU, the supernatant showed autocrine growth-promoting activity which strongly stimulated DNA synthesis of 3 renal-cancer cell lines in a dose dependent manner. Activity could be detected in a 4- to 6-kDa fraction by gel filtration. This fraction increased the DNA-synthesis-promoting activity of epidermal growth factor, transforming growth factor-beta, basic fibroblast growth factor and insulin, and was acid- and heat-stable. It was also stable against pepsin and dithiothreitol. DNA synthesis in BALB/c 3T3, adult rat hepatocytes and rabbit renal tubular cells was not affected by this fraction which was thus considered not to affect non-cancerous cells. Renal-cell carcinoma responds poorly to anticancer agents, and the autocrine activity of the fraction may possibly be a factor accounting for this resistance. PMID- 1500216 TI - Human carcinoembryonic antigen cDNA expressed in rat carcinoma cells can function as target antigen for tumor localization of antibodies in nude rats and as rejection antigen in syngeneic rats. AB - We have tried to develop a new model consisting of rats transplanted with syngeneic colon carcinoma PROb cells transfected with cDNA coding for the carcinoembryonic antigen (CEA), the human tumor marker most commonly used as target for MAbs. The antigenic density of the 4 CEA-expressing clones selected for a precise characterization ranged from 5 x 10(4) to 1 x 10(6) CEA molecules per cell. In all clones the CEA was shown to be attached to the membrane by a phosphatidylinositol (PI) anchor. Using a panel of radiolabeled MAbs directed against the 5 major epitopes described on the CEA molecule, we showed that all these CEA epitopes were expressed by the 4 transfectants. Southern-blot analysis showed that the entire CEA cDNA was present in the transfectants. Western-blot analysis, however, showed that the size of the CEA expressed by the 4 transfectants was slightly smaller than that of CEA produced by 2 reference human colon-carcinoma cell lines. Two clones, expressing 1 x 10(5) and 1 x 10(6) CEA molecules per cell, respectively, were grafted s.c. in nude mice and rats. Injection of radiolabeled anti-CEA F(ab')2 fragments into these animals showed specific tumor localization with the highest percentages of injected doses for the transfectants expressing the highest CEA level. When grafted into immunocompetent syngeneic BDIX rats, the CEA-expressing clones induced a strong antibody response against CEA and tumor rejections in a majority of the animals. Although the analysis of the immune response against the CEA-cDNA-transfected carcinoma cells is under investigation, the present results demonstrate that human CEA could function as a rejection antigen when transfected into rat carcinoma cells. PMID- 1500217 TI - Establishment and characterization of human uterine leiomyosarcoma heterotransplanted into nude mice. AB - Human uterine leiomyosarcoma is a rare gynecological malignancy with a generally poor prognosis. We have established a human uterine leiomyosarcoma tumor line in nude mice, designated UTS-1, and describe the characteristics of this tumor. The UTS-1 tumor doubled in 12.1 days and retained the histological characteristics of leiomyosarcoma, even after 14 serial generations. Ultrastructurally, the tumor is characterized by nuclear pleomorphism typical of smooth muscle, intracytoplasmic filaments with dense bodies, a relative paucity of micropinocytotic vesicles, and an incomplete external lamina. Immunohistochemically, the UTS-1 cells reacted with antibodies against vimentin, desmin, smooth-muscle actin and myosin, but not with antibodies against keratin, CEA and S-100 protein. Serum levels of AFP, CA125, CEA and SCC ranged within normal limits in tumor-bearing mice. The serum level of immunosuppressive acidic protein correlated well with an activity of the tumor. Estrogen and progesterone receptors were not detected in the tumor. Chromosomal analysis showed a human karyotype with some marker chromosomes and a modal number of 85 chromosomes. The UTS-1 tumor should prove a useful model to explore the biological characteristics and treatment of human uterine leiomyosarcoma. PMID- 1500218 TI - Expression of p53 protein in cutaneous melanoma. AB - The purpose of the present study was to examine the expression of p53 protein in malignant melanomas of the nodular sub-type, with special reference to the role of p53 alterations in the development of metastases. Increased expression of p53 protein was found in 29 of 30 cases using PAb1801 monoclonal antibody (MAb) and flow-cytometric detection on archival material. A large proportion of the cells were positive in a majority of the cases. The level of expression was not correlated to DNA ploidy or to subsequent development of local metastases. However, a significant decrease in p53 protein expression was observed in metastatic lesions, as compared with the corresponding primary tumors. Our results indicate that p53 alterations may be an early event in melanoma development, since almost all cases were affected, and that metastatic spread appears to be parallelled by decreased p53 protein expression. PMID- 1500219 TI - Effect of MHC class-I transfection on local tumor growth and metastasis in an H-2 negative clone derived from a chemically induced fibrosarcoma. AB - GR9 is a chemically induced fibrosarcoma composed of clones with different H-2 class-I expression. These clones differ with respect to local growth and spontaneous metastasis. The B9 clone (H-2 negative) is highly tumorigenic (local growth) but of low metastatic potential (spontaneous metastasis assay). We have analyzed the effect that transfection of H-2Dd and H-2Kd genes on this clone have upon local growth, lung colonization after i.v. injection and ability to form spontaneous metastases. The results showed that the effect on local growth of transfection of the Kd-gene was stronger than that of the Dd gene. In addition, B9 co-transfected with H-2Kd and Dd genes showed the highest immunogenic properties in syngeneic BALB/c mice. Interestingly, the pSV2-neo transfected clone gave almost the same result as that obtained with Dd transfection. Lung colonization after i.v. injection of the different clones (experimental metastasis), paralleled the results obtained for local growth: the number of lung nodules followed the cadence KdDd less than Kd less than Dd less than pSV2. Survival of mice was always inversely correlated with local growth, e.g., all mice injected with 5 x 10(5) B9 H-2KdDd transfected cells survived. In contrast, no mice injected with the B9 control did. These differences were abrogated in irradiated and nude BALB/c mice. Finally, all transfected clones remained non metastatic in a spontaneous metastasis assay, behaving as the control, non transfected B9 cells. PMID- 1500220 TI - Risk factors for skin melanoma in Moscow. PMID- 1500221 TI - Synthetic ether lipids fluidizing action and cell membrane lipid composition: a commentary note. PMID- 1500222 TI - Aspects of medical history and exocrine carcinoma of the pancreas: a population based case-control study in The Netherlands. AB - During 1984-88 a population-based case-control study was carried out in The Netherlands, in collaboration with the International Agency for Research on Cancer, to examine the possible relationship between aspects of medical history and exocrine pancreatic carcinoma in 176 cases and 487 controls. About 58% of patients were interviewed directly. We observed an inverse relationship between medical treatment for allergy-related conditions and the development of pancreatic cancer (30 cases vs. 130 controls, OR 0.57, 95% CI 0.36 to 0.90). A history of gallbladder problems, gallstones, cholecystectomy, stomach or duodenal ulcer, pancreatitis, appendicitis, diabetes or tonsillectomy was not related to risk. In direct responses, compared with once daily, a positive relationship was seen for stool frequency, 10 years ago, of less than once daily (18 cases vs. 40 controls, OR 2.10, 95% CI 1.09 to 4.04). In men, diabetes treated with insulin and diagnosed more than 1 year previously was significantly and positively related to risk (5 cases vs. 1 control, OR 11.66, 95% 1.28 to 105.95). In brief, the results of the present study suggest that a history of allergy-related conditions may protect, whereas a past stool frequency of less than once daily may enhance the risk of cancer of the pancreas. Other elements of the medical history were not consistently related to risk. PMID- 1500223 TI - Anthropometric and reproductive variables and exocrine carcinoma of the pancreas: a population-based case-control study in The Netherlands. AB - During 1984-88 a population-based case-control study was carried out in The Netherlands, in collaboration with the International Agency for Research on Cancer, to examine the possible relationship between aspects of medical history and exocrine pancreatic carcinoma in 176 cases and 487 controls. About 58% of patients were interviewed directly. In women, a significant, positive dose response effect of height was seen (p-value trend less than 0.005). Compared with ages 14 or more, women with an early age at menarche, i.e., 11 years or less, had a 3-fold increase in risk (15 cases vs. 23 controls, OR 3.07, 95% CI 1.35 to 7.00). Other apsects of the reproductive history were not related to risk. In brief, the results of the present study support the hypothesis that, in women, early menarche and greater adult stature may be early predictors of the development of cancer of the pancreas later in life. PMID- 1500224 TI - K-ras point mutations in human colorectal carcinomas: relation to aneuploidy and metastasis. AB - Material from paraffin sections of 109 human colorectal carcinomas, mostly obtained at autopsy, was analyzed for the presence of K-ras point mutations at codon 12, position 2. Mutations at this position were found in 23 cases (21.1%). Aneuploid colorectal carcinomas showed a significantly higher prevalence of K-ras point mutations than diploid tumors, suggesting an involvement of ras mutations in the development of aneuploidy. No differences in the prevalence of K-ras mutations were observed with respect to the patients' age, sex and tumor type. In metastases, the type of ras gene mutation was always identical to that of the respective primary tumor. Mutations were not found in metastases from primary tumors devoid of ras mutations. This renders a clonal selection of K-ras mutated cells from a wild-type primary tumor during the metastatic process unlikely. However, nearly twice as many ras gene mutations were seen in metastatic than in non-metastatic primary tumors. PMID- 1500225 TI - Immunoreactivity, pharmacokinetics and bone marrow dosimetry of intrathecal radioimmunoconjugates. AB - Ten patients with neoplastic meningitis were treated with a variety of 131I monoclonal antibody (MAb) conjugates, chosen to bind to their particular malignancy. Pharmacokinetic studies revealed that MAbs leave the ventricular compartment, enter the sub-arachnoid space and then pass into the blood. Once the MAbs enter the blood compartment, their clearance is determined by factors such as circulating anti-mouse Ig and circulating antigens. These lead to complex formations and the clearance of the conjugate by the reticuloendothelial system. In one individual, the anti-mouse Ig response observed systemically was not mirrored within the CSF, which has implications for planning future therapy of this type. In other patients, formation of immune complexes was due to binding to circulating antigen within the blood. The major toxicity associated with the intrathecal administration of 131I-MAbs was bone-marrow suppression. The doses to the bone marrow, resulting from the form of therapy, were calculated but showed no direct correlation with WHO grade 3/4 toxicity. Doses to the ventricular lining were also calculated, but due to the complex geometry of the compartment, calculation of potential tumour doses was not practicable. PMID- 1500226 TI - Micronuclei in bronchial biopsy specimens from heavy smokers: characterization of an intermediate marker of lung carcinogenesis. AB - Bronchial micronuclei, small fragments of extra-nuclear DNA formed during cell division, provide a non-specific but quantifiable marker of DNA damage. Micronuclei have been used to assess carcinogen exposure and as an intermediate endpoint in chemoprevention trials. As part of an ongoing chemoprevention trial, heavy smokers underwent screening bronchoscopy, with biopsies taken at 6 standardized sites. Micronuclei counts were obtained for each site in each of the 40 volunteers found to have squamous metaplasia. Unlike squamous metaplasia, the average micronuclei counts among these heavy smokers were not associated with smoking history. Micronuclei counts were also not associated with the presence or extent of metaplasia. A striking degree of intra-individual variability was observed by comparing the micronuclei counts from different biopsy sites within individuals. The findings suggest that use of micronuclei from single sites may be misleading as a marker of carcinogen exposure or as an estimate of cancer risk. Serial measurements in individuals may provide the most useful information concerning carcinogenic exposure and the impact of chemopreventive agents. PMID- 1500227 TI - Breast cancer in a low-risk population. The influence of age and menstrual status on disease pattern and survival in Saudi Arabia. AB - Data on 130 women with invasive breast cancer, seen at our institution between April 1981 and November 1990, were retrospectively reviewed to assess the influence of age and menstrual status on the pattern and prognosis of their disease. Patients were mostly young (median age 40 years) and in 21 patients (16%) the diagnosis was established at the age of 30 years or younger. Eighty-six patients (66%) were under 50 and 82 patients (63%) were pre-menopausal. Pre menopausal patients were more numerous than expected in stage III and less numerous in stage II. On the other hand, the differences between observed and expected values for both stage I and stage IV in the 2 menopausal groups were not significant. Compared with post-menopausal patients, pre-menopausal patients with 1-3 or greater than 3 positive lymph nodes were more numerous than expected. Differences between pre-menopausal and post-menopausal patients have persisted after categorizing patients into 2 age-groups with a cut-off point at 50 years. Comparable initial assessment and therapeutic modalities were offered to the 2 menopausal groups. At the time of analysis (January, 1991) all patients had a complete follow-up. Over a median follow-up of 46 months, the overall median survival (+/- SE) was 85.7 (+/- 4.4) months with a survival probability (+/- SE) at 5 years of 62% (+/- 5%). The proportional hazard model of Cox has identified advanced stage (stages III and IV) and involvement of lymph nodes as the only independent adverse predictors of survival with estimated hazard rates of 2.9 and 2.8, respectively. Unadjusted analysis, adjusted analysis and stratified survival functions failed to reveal any survival difference based on age or menstrual status. We conclude that, in a low-risk population and despite apparent baseline differences in demographic and disease characteristics between pre-menopausal and post-menopausal breast cancer patients, neither age nor menopausal status had a significant influence on survival. Our results should guide future cancer-care programs in Saudi Arabia. PMID- 1500228 TI - Distribution of autologous tumor-specific cytotoxic T lymphocytes in human metastatic melanoma. AB - The study of specific immunity in human cancers has been hampered by the elusive distribution and heterogeneity of effector cells. In this study, we have investigated the distribution of autologous melanoma-specific cytotoxic T lymphocytes (CTLs) in 18 different distant metastases from melanomas (9 non visceral and 9 visceral metastases). Uncultured cells from tumors were provided directly for the establishment of T-cell clones using limiting dilution analysis to avoid any possible effects of in vitro sensitization of T cells to coexisting tumor cells. Autologous tumor specific CTL clones were detected in 6 of 18 tumors (33%, 4 non-visceral and 2 visceral metastases). The majority of CTL clones (35 of 46 and 17 of 19) in 2 patients with HLA class-I A2 haplotype failed to lyse either A2+ or A2- allogeneic melanoma cells, although anti-class-I (monomorphic) MAb inhibited their cytotoxicity. The remaining 11 of 46 and 2 of 19 CTL clones showed A2-restricted cytotoxicity. Autologous tumor-specific cytotoxicity was also detected after polyclonal culture of these tumor-infiltrating lymphocytes (TILs) in 8 of 16 tumors (50%, 5 non-visceral and 3 visceral metastases). These results suggest that tumor-specific T cells exist at tumor sites in at least one third of distant metastases of melanomas and could be induced by the addition of IL-2 in at least half of the tumors. Tumor-specific T cells were detectable more often in non-visceral than in visceral metastases. PMID- 1500229 TI - Expression of histo-blood-group-A/B-gene-defined glycosyltransferases in normal and malignant epithelia: correlation with A/B-carbohydrate expression. AB - Malignant transformation of oral and bladder epithelia is often associated with loss of histo-blood-group-A- and -B-carbohydrate antigens, whereas these antigens, which are absent in normal adult distal colon (but present in fetal colon) reappear in malignant distal colon. In order to gain insight into the genetic basis of the biosynthetic regulation for these changes, we have correlated the expression of the A- and B-carbohydrate antigens with that of the A/B-gene-defined glycosyltransferases in colon, bladder and oral carcinomas by immunohistology. A newly developed anti-A/B-transferase monoclonal antibody (MAb) was used to demonstrate the in situ localization of transferase expression at the individual cell level with correlation to carbohydrate antigen expression, and gave the essential information that the transferase is derived from the ABO gene complex. The reappearance of A- and B-carbohydrate antigens in carcinomas of the distal colon was found to be unrelated to the expression of the A/B-transferase proteins, which were expressed throughout normal adult colon in accordance with previous enzymatic studies. In contrast, the loss of A- and B-carbohydrate antigens in malignant bladder and oral epithelia was accompanied by concordant loss of enzymes. PMID- 1500231 TI - Orthotopic and ectopic organ environments differentially influence the sensitivity of murine colon carcinoma cells to doxorubicin and 5-fluorouracil. AB - We determined the effects of organ environment on the response of murine CT-26 colon carcinoma cells to 2 structurally and pharmacologically distinct chemotherapeutic agents. CT-26 cells were injected i.v. (to produce lung lesions), s.c., into the cecal wall, and into the spleen (to produce spleen and liver lesions). Doxorubicin (DXR) at 10 mg/kg, 5-fluorouracil (5-FU) at 20 mg/kg, or saline (control) was injected intravenously on different schedules after tumor cell implantation. The in vivo responses of the tumors growing in the cecum, spleen, liver, lung and subcutis were compared. Colon carcinomas growing in the subcutis were most sensitive to DXR. Tumors growing in the spleen and cecum were most sensitive to 5-FU and less so to DXR. Tumors in the liver were highly resistant to both drugs, whereas experimental lung metastases were sensitive to 5 FU but resistant to DXR. The differential responses of the tumors to the drugs were not due to drug distribution. The level of protein-kinase-C activity was elevated in the spleen, liver and cecum tumors as compared with s.c. tumors and correlated with the in vivo DXR resistance of the tumor cells. This correlation suggested that organ environment may modulate the chemosensitivity of tumor cells, at least in part, by perturbing signal transduction pathways. Collectively, the data indicate that the organ environment has profound effects on the response of tumor cells to chemotherapy. A molecular understanding of this phenomenon should facilitate the design of more effective systemic chemotherapy for cancer metastases. PMID- 1500230 TI - Morphological, immunohistochemical and biochemical characterization of 6 newly established human ovarian carcinoma cell lines. AB - Six permanent human tumor cell lines (OV-MZ-1 to 6) were established from 6 patients with serous adenocarcinomas of the ovary. These cell lines were derived from both solid tumors and ascites, from pre-treated and untreated patients, and are available over a range of in vitro passage numbers. The tumor cells grow as monolayers and develop foci of "piled-up' cells in confluent cultures. Flow cytophotometry showed that all the lines exhibited DNA hyperdiploidy with DNA tetraploidy in one cell line and DNA aneuploidy in the other cell lines. The mean population doubling time ranged from 24 to 52 hr. Transmission electron microscopy demonstrated that the tumor cells of all cell lines exhibited features of epithelial differentiation such as desmosomes and intracellular gland-like lumina. Immunocytochemical analysis showed that the co-expression of cytokeratins and vimentin, which is a feature of ovarian serous cystadenocarcinomas in situ, was fully preserved in the majority of cell lines. The main cytokeratin polypeptides expressed were numbers 7, 8, 17, 18 and 19. The tumor-associated antigen CA-125, but not CEA, was shed in the culture supernatant. This was in accordance with FACScan analysis of the cell lines and the level of CA-125 and CEA in the patients' serum. The estrogen and progesterone receptors were negative both in the cell lines and in the original tumors. These new ovarian carcinoma cell lines will be valuable models for further investigations into a variety of biological properties. PMID- 1500232 TI - Disorders of the nails and hair associated with human immunodeficiency virus infection. PMID- 1500233 TI - Cutaneous hyperpigmentation caused by systemic drugs. PMID- 1500235 TI - AIDS-related Kaposi's sarcoma. PMID- 1500234 TI - Collagen injections. PMID- 1500236 TI - Subspecialty electives in dermatologic surgery. PMID- 1500238 TI - Confluent and reticulated papillomatosis: clinical, light and electron microscopic studies. AB - A case of a 17-year-old Japanese-Canadian boy with a 2-year history of skin lesions relevant to confluent and reticulated papillomatosis (CRP) is reported with electron microscopic findings. He had scattered skin lesions of brownish colored, rough-surfaced, fine-scaled patches and plaques distributed on the nape, shoulders, and both flanks, extending to the chest and back. Importantly, they showed reticular or confluent arrangement. There was no family history of the same skin lesions. The histology showed epidermal papillomatosis and mild acanthosis with a marked hyperkeratosis. Electron microscopically, the skin lesions consisted of the following abnormal findings: (1) a marked alteration of cornified cell structures showing snake coil-like, or triangle-like stacks, (2) a marked increase in the number of lamellar granules in the granular layer, (3) an increased number of melanosomes in the horny layers, and (4) no significant fine structural changes of epidermal melanocytes. This is the first electron microscopic report on CRP suggesting that the pathophysiology of this disease is related to abnormal keratinocyte differentiation. PMID- 1500237 TI - Porphyria cutanea tarda and human immunodeficiency virus infection. AB - Porphyria cutanea tarda (PCT), a relatively uncommon disease, has recently been reported in patients infected with the human immunodeficiency virus (HIV). Although PCT and HIV infection may co-exist by chance, the increasing number of reported cases suggest that HIV or an associated factor triggers the development of PCT in predisposed individuals. We report four additional cases of PCT in HIV seropositive patients and review the previously reported cases. The possible links between PCT and HIV are discussed. We believe the diagnosis of PCT should prompt investigation for HIV infection in all patients. PMID- 1500239 TI - Joint complaints in psoriasis patients. AB - Four hundred and fifty-nine psoriasis patients seen at the Department of Dermatology, Bowman Gray School of Medicine of Wake Forest University, responded to a questionnaire concerning current or past joint complaints. Of these, 17% reported a previous diagnosis of psoriatic arthritis, and over 53% had a current or past history of arthralgias. Additional information on those patients reporting arthralgias focused on the cutaneous sites of involvement with psoriasis and which joints were most likely to be involved in patients with various types of arthritis. Previous treatments for skin involvement with psoriasis were more aggressive in those patients with a diagnosis of psoriatic arthritis. A significant proportion of patients presenting to dermatologists for treatment of psoriasis have joint complaints, and the percentage of patients with psoriatic arthritis is greater than generally appreciated by non-dermatologists. PMID- 1500240 TI - Squamous cell carcinoma in southern and northern Australia. AB - Squamous cell carcinoma (scc) of the skin was studied in two similar populations, one living in the temperate zone of Australia, the other living in the tropics. In the tropics, the patients were significantly younger, the man to woman ratio approached unity, and women had significantly more sccs on the legs. In the temperate zone, men had significantly more on the head and neck, but women had significantly more on the upper and lower limbs. PMID- 1500241 TI - Dermatology in a war zone: a Persian Gulf experience. AB - The clinical experience of two US Army dermatologists during the recent Gulf War (Operation Desert Shield/Storm) are presented with comparison with dermatologic experience in previous wars and in civilian practice. PMID- 1500242 TI - Nonbullous bullous pemphigoid. AB - Three patients had a rare form of bullous pemphigoid, clinically similar to the erythematous type of bullous pemphigoid without vesiculobullous lesions. All the patients displayed immunofluorescence features of bullous pemphigoid. This form of the disease presents a substantial diagnostic problem because it lacks the principal morphologic feature of bullous pemphigoid, namely the vesicles and bullae. PMID- 1500243 TI - White piedra in Saudi Arabia. PMID- 1500244 TI - Tuberculosis verrucosa cutis arising from a trophic ulcer. PMID- 1500245 TI - Scrofuloderma and caries spine. PMID- 1500246 TI - Roseolar lesions in Lyme disease: isolation of the causative agent. PMID- 1500247 TI - Vesicular graft-versus-host disease. PMID- 1500249 TI - Alopecia universalis treated with oral cyclosporine A and prednisolone: immunologic studies. AB - Alopecia universalis is a refractory condition. Although the cause of this disease is unknown, immunologic abnormalities have recently been suspected. Thus, we treated six cases of refractory alopecia universalis with immunotherapy. Oral administration of cyclosporine A (2.5 mg/kg) and prednisolone (5 mg/day) resulted in marked symptomatic improvement. Cyclosporine A did not produce any side effects because the administered dosage was relatively low. At present, more than 6 months after the cessation of treatment, recurrence of alopecia has not been seen. Oral administration of low-dose cyclosporine A and prednisolone is considered to be an effective treatment for this disease. Immunologic examination of peripheral blood demonstrated improvement of immunologic function. In particular, CD8-positive T cells, NK cells, and C3, which had been reduced, were increased. A reduction in active CD4 cells, eosinophils, and circulating immune complexes was observed. Histology with fluorescent antibodies showed T-cell infiltration around the hair matrixes. This phenomenon was no longer observed after treatment. These improvements in immunologic function were seen in parallel with the resolution of the clinical symptoms, indicating that immunologic abnormalities are related to this disease. PMID- 1500248 TI - Systemic ketoconazole treatment for Fusarium leg ulcers. AB - Fusarium oxysporum was isolated from a large foot ulcer in an otherwise healthy 69-year-old man. Although tissue invasion could not be proven histologically, systemic antifungal treatment was administered with satisfactory response. Fusarium species are common soil-inhabiting organisms and plant pathogens. In humans, Fusarium is considered an opportunistic agent in skin ulcers, interdigital spaces, and burned skin, but can also cause mycotic keratitis, onychomycosis, and rarely deep-seated or disseminated infections, especially in an immunocompromised host. The distinction between skin infection and saprophytic growth, as well as optimal treatment regimens for the two types of infection, have not been clearly defined. We describe a case of leg ulcers caused by Fusarium oxysporum in a 69-year-old man treated successfully with oral ketoconazole. "Silent" immunologic disturbances were found in this apparently healthy patient. The case illustrates a relatively benign infection caused by Fusarium that responded to systemic antifungal drug treatment. PMID- 1500250 TI - Severe acute form of adult dermatomyositis treated with cyclosporine. AB - The classical treatment of severe forms of dermatomyositis includes high doses of steroids and/or cytotoxic agents. Acute forms are frequently life threatening. Because cyclosporine is a fast-acting immunosuppressive drug, it appears to be a good candidate for the treatment of refractory forms of acute dermatomyositis. We report a dramatic improvement of a severe, acute, steroid-resistant adult form after cyclosporine administration. A rapid clinical and biochemical improvement is reported, and the reversibility of immunologic abnormalities is emphasized. PMID- 1500251 TI - Cyclosporine in dermatology: a historical overview. PMID- 1500252 TI - Hyperkeratosis nigricans. PMID- 1500253 TI - The "ugly and the beast". PMID- 1500254 TI - Trace elements in serum of pityriasis alba patients. PMID- 1500255 TI - [Malaria]. PMID- 1500256 TI - [Pregnancy and cardiac diseases]. PMID- 1500257 TI - [Lung diseases and pregnancy. Risks and therapeutic possibilities]. PMID- 1500258 TI - [Gastroenterologic diseases and pregnancy. Esophagus, stomach, intestine]. PMID- 1500259 TI - [Gastroenterologic diseases and pregnancy. Liver, bile ducts, pancreas]. PMID- 1500260 TI - [Pregnancy and infectious diseases]. PMID- 1500261 TI - [Psychosomatic problems in pregnancy]. PMID- 1500262 TI - [53-year-old patient with plethora, colic and dark urine]. PMID- 1500263 TI - [Ultra-high dose streptokinase therapy of catheter-induced superior vena cava syndrome in Crohn disease]. PMID- 1500264 TI - A phase II study of crisnatol mesylate in patients with ovarian carcinoma. AB - Fourteen patients with advanced ovarian cancer received a 72 hour infusion of a new DNA intercalator, crisnatol mesylate, administered intravenously. There was no evidence of antitumor efficacy. A syndrome of nausea and vomiting associated with vertigo, dizziness and ataxia was observed in nearly all patients. Two of the patients developed severe CNS toxicity manifested in one by a grand-mal seizure and in the other by peripheral neuropathy. Further explorations into the potential efficacy of crisnatol mesylate administered intraperitoneally are underway. PMID- 1500265 TI - Phase II clinical and pharmacological study of didemnin B in patients with metastatic breast cancer. AB - Sixteen evaluable patients with metastatic breast cancer were entered into a phase II trial of didemnin B. They received the drug at an initial dose of 5.6 mg/m2 every 21 to 28 days. Major toxicities noted were myalgia and nausea and vomiting while myelosuppression was mild. There were no complete responses; however, two minor responses were observed. The pharmacokinetics of didemnin B were studied in 10 patients who received the drug as 30 to 60 min i.v. infusions. A sensitive competitive inhibition enzyme immunoassay was used to quantitate didemnin B levels. Drug was observed to be rapidly cleared from plasma in a biphasic manner (t1/2 alpha = 0.12 hr, t1/2 beta = 4.8 hr). Although the assay could not identify the presence of specific metabolites, the increase of apparent didemnin B levels in plasma at later time points suggested the formation of unidentified metabolites which cross reacted with the antibody in the analytical procedure. In vitro experiments indicated that didemnin B was not bound to bovine serum albumin and only a minor portion (24%) of drug was found associated with red blood cells. PMID- 1500266 TI - Phase II clinical study of pirarubicin in hormone resistant prostate cancer. AB - Twenty one patients with hormone resistant prostate cancer were entered in a phase II study of pirarubicin 70 mg/m2, as a single intravenous injection given at 21 day intervals. All patients had leukopenia (9 severe or life threatening) and 2 died of septicemia. Thrombocytopenia occurred in 5 patients (one life threatening) and anemia in 12 patients. One partial response of 3 months duration was documented. Pirarubicin 70 mg/m2 given intravenously at 21 day intervals causes severe hematological toxicity and has minimal therapeutic activity in patients with hormone resistant prostate cancer. PMID- 1500267 TI - Phase II evaluation of piroxantrone in renal cell carcinoma. A Southwest Oncology Group Study. AB - The Southwest Oncology Group (SWOG) studied the response rate and toxicity of piroxantrone (150 mg/m2 q 21 days) in patients with advanced metastatic renal cell carcinoma. Among 32 eligible patients, there were no partial nor complete responses. There were two mixed responses. Significant white cell toxicity, anemia, nausea, and vomiting were observed. Mild or moderate degrees of fever, malaise, and stomatitis occurred. No significant cardiac toxicity was noted. Piroxantrone does not have significant activity as a single agent in advanced renal cell carcinoma. PMID- 1500268 TI - Evaluation of in vitro drug screening leads using experimental models of human ovarian cancer. AB - Five compounds which were identified as potential new anticancer drugs in in vitro screening with the human tumor colony forming assay were selected for further evaluation using in vitro and in vivo models of human ovarian cancer. Three of five compounds were found to inhibit in vitro colony formation of ovarian cancer cell lines derived from both untreated and combination chemotherapy refractory patients. One compound was also found to prolong survival in a human ovarian carcinoma xenograft model system. This compound, chloroquinoxaline sulfonamide, was selected for development and has shown preliminary indication of activity in phase I clinical testing. PMID- 1500269 TI - Bis-daunomycin hydrazones: interactions with DNA. AB - A series of bis-daunomycin hydrazones were synthesised from diester diamide linking groups derived from alpha,omega-dicarboxylic acids. All members of the series bis-intercalated into DNA, as evidenced by doubling of the lengthening of rod-like DNA compared to daunomycin, and by a 1000-5000 fold slower dissociation from DNA than daunomycin under detergent sequestration conditions. The bis hydrazones exhibited neighbour exclusion, and occupied 6 bp under saturating conditions of drug. A unique DNA sequence specificity was apparent from transcriptional footprinting of 100 bp of DNA, with the greatest preference for 5'-CACA sites. PMID- 1500270 TI - Phase II trial of 5 day continuous intravenous infusion of 6-thioguanine in patients with recurrent and metastatic squamous cell carcinoma of the head and neck. AB - Fifteen patients with recurrent and/or metastatic squamous cell carcinoma of the head and neck received a 5 day continuous I.V. infusion of 6-thioguanine repeated every five weeks. Dose limiting toxicity was primarily hematological with grade III/IV leucopenia and thrombocytopenia seen in seven patients. Nausea and vomiting was moderate and well controlled with antiemetics. No complete or partial responses were observed, with a median time to progression of 58 days and a median survival of 227+ days for the entire group. Based on these results we do not recommend I.V. 6-thioguanine for the treatment of this disease. PMID- 1500271 TI - Oral piritrexim--a phase II study in patients with advanced soft tissue sarcoma. PMID- 1500272 TI - Phase II study of amonafide in advanced and recurrent sarcoma patients. AB - The activity of amonafide, a benzisoquinoline-1,3-dione, was assessed in 15 patients with advanced or recurrent sarcoma (11 previously treated). Eligible patients had ECOG performance status 0-2, and acceptable renal, hepatic and bone marrow function. Amonafide 300 mg/m2 was given intravenously over one hour daily on five consecutive days, every 3 weeks. Leukopenia and granulocytopenia were the most common and severe toxicities (grade 3 or 4 toxicity in 20% and 27% of patients, respectively). Local irritation and nausea/vomiting, the most common nonhematologic toxicities, were generally mild. No objective responses were seen, though 2 patients had brief stabilization of disease. Amonafide at this dose and schedule has no activity against advanced, recurrent sarcoma. PMID- 1500273 TI - Coat protein properties suggest that azuki bean mosaic virus, blackeye cowpea mosaic virus, peanut stripe virus, and three isolates from soybean are all strains of the same potyvirus. AB - The interrelationship of a number of potyviruses infecting legumes has been investigated by comparing molecular properties of their coat proteins. Comparison of the coat proteins by the techniques of amino acid analysis and PAGE was inadequate to distinguish strains from distinct potyviruses. However, high performance liquid chromatographic peptide profiles of tryptic digests of coat proteins of these legume-infecting potyviruses enabled such assignments to be made. These data indicate that amino acid sequences of coat proteins of azuki bean mosaic virus, the Type and W strains of blackeye cowpea mosaic virus, three isolates (74, PM, PN) of a potyvirus obtained from soybean in Taiwan, and the Blotch and Mild Mottle strains of peanut stripe virus (PStV) may be very similar to the known sequence of PStV Stripe coat protein. In contrast, peptide profiles of coat proteins from soybean mosaic virus, clover yellow vein virus, bean yellow mosaic virus, potato virus Y, and tobacco etch virus were dissimilar to each other and to the profile of PStV Stripe, suggesting that their coat protein sequences were also quite different. Based on observations of the coat protein structure of many potyviruses, the results suggest that the potyvirus isolates with similar coat proteins are strains of the same potyvirus. PMID- 1500274 TI - Mapping and sequence analysis of the capsid protein gene of cowpea mottle virus. AB - Twelve cDNA clones were generated, covering approximately 95% of the cowpea mottle virus (CMeV) genome from the 3' end to near the 5' end. The entire capsid protein sequence of 1,104 nucleotides was contained in two clones located near the 3' terminus. The codons represented 367 amino acids (M(r) 39,611). The postulated amino acid sequence of CMeV capsid protein had 36% homology to turnip crinkle virus and 26% homology to carnation mottle virus in the arm and S domains, but western blots showed no serological relationship to either. On the basis of the organization and expression of its genome and its physicochemical properties, CMeV is assigned to the carmovirus group. Like other carmoviruses, CMeV generates three dsRNAs which are co-terminal at the 3' end in infected tissues, but CMeV differs from other carmoviruses in the absence of encapsidated subgenomic RNAs. PMID- 1500275 TI - A topological model for hepatitis B surface antigen. AB - A model of hepatitis B surface antigen has been derived, based on extensive sequence analysis and biochemical data. The surface antigen sequences of the human, woodchuck, ground squirrel and duck hepadnaviruses were examined using hydrophobicity, hydrophobic moments, flexibility and secondary structure prediction. The helix phase diagram, which is a modified version of Eisenberg's hydrophobic moment plots and which specifically addresses the problem of transmembrane helices, was used to examine the predicted helices. In this model four transmembrane helices are predicted. The N and C termini and the second hydrophilic region, which bears the major B-cell antigenic determinants, are external. It is suggested that the transmembrane helices may pack to form a channel through the membrane and may also be involved in the mechanisms of cell entry. A significant difference between the duck hepadnavirus and the mammalian HBsAg sequences was found, hence care must be taken when extrapolating data between the duck and the human surface antigen. PMID- 1500276 TI - Cytoplasmic localization of the DNA virus frog erythrocytic virus. AB - In situ hybridization, using a biotinylated clone of frog erythrocytic virus (FEV), was conducted to determine the location of viral sequences in bullfrog erythrocytes. FEV-specific hybridization signals were found to correspond to mature cytoplasmic viral particles and assembly sites. These data are consistent with electron microscopic observations of viral assembly in the erythrocyte cytoplasm. Although FEV has morphological and biochemical properties similar to frog virus 3, our data suggest that the site of DNA replication and assembly of FEV is more similar to that of the poxviruses. PMID- 1500277 TI - Intravenous nutritional support and the surgeon: where next? AB - Over the past twenty five years the development of total parenteral nutrition has in many ways revolutionised the practice of surgery. It has enhanced survival in otherwise high mortality operations such as oesophageal surgery, especially with anastomotic complications. It has changed significantly the management of fistulae, either post operative or associated with diseases such as Crohn's enteritis. Here a basic general principle is applied--that a fistula will close if there is no distal obstruction and the throughput can be diminished. This can be achieved by withholding oral feeding and using the parenteral route. It has allowed survival in the short gut syndrome from whatever cause and it is interesting to see the degree of "intestinal adaptation" that occurs once the first critical year is survived with the help of intravenous nutrition. The assessment of nutritional status is difficult and while the level of serum albumin may be taken as a clinical standard, it is obvious that many patients survive extensive surgery with low albumin levels and also that there appears to be a lag period to the restoration of albumin levels, even with otherwise successful nutritional support and with other parameters being satisfactory. Even complex formulae using a combination of laboratory and antropometric parameters is not fully satisfactory as an absolute assessment of nutritional status. It is now interesting to see that nutrition can affect both immune competence and even carcinogenesis. The lipid element in intravenous nutrition may cause dysfunction of immunity and vitamin status, gastric and platelet function with impaired oxygen diffusion leading to increased wedge pressures.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1500278 TI - Transfusion therapy in elective total hip arthroplasty. AB - A retrospective audit of transfusion practice in 150 consecutive elective primary total hip arthroplasties was undertaken, to examine blood usage and to determine the potential for reduction in its use. Predetermined criteria were used to measure unnecessary transfusions. Transfusion was considered unnecessary if the discharge haematocrit exceeded 36%, or if patients who lost less than 30% of their estimated blood volume, were transfused. Using these criteria, overtransfusion occurred in 42-45% patients. The intra-operative blood transfused correlated well with intra-operative blood lost. All other variables showed no significant correlation with both intra-operative and post-operative blood transfused. Females lost less and were transfused significantly more than males. The study corroborates previous reports of blood overuse. These results suggest that adopting standards of practice to measure and to monitor transfusion practice (quality assurance programmes) would be a worthwhile objective. PMID- 1500279 TI - Interactive video learning in medical school. PMID- 1500280 TI - Osborne of Dublin and the origin of nephrology in Ireland. PMID- 1500281 TI - Factors affecting glycosaminoglycan concentration in normal human plasma. AB - Acid Glycosaminoglycans (GAGs) were measured, in terms of hexuronic acid, following alkaline treatment and Ecteola chromatography, in plasma obtained from healthy volunteers, blood-donors, amateur soccer players and university students, and from hospitalized subjects at the end of their convalescence. Diurnal variations of plasma GAG concentration, with significant decrease during the morning, were obtained in students and patients, suggesting hormonal influences. Furthermore, moderate modifications of plasma GAG concentration were observed in students following cyclo ergometer exercise which were consistent in each subject with cortisol mediated changes. However, the absolute value of plasma GAG concentration appears to be depending on the physical training of the subject, being significantly higher in the soccer players and in the blood-donors than in the other groups of subjects, chiefly composed of sedentary individuals. The intramuscular connective tissue is then suggested to represent a main site of origin of plasma GAGs. PMID- 1500282 TI - Fructose 1,6-bisphosphate-activated pyruvate kinase from E. coli: ligand promoted conformational changes. AB - The ligand-dependent susceptibility to heat inactivation and to tryptic digestion and the intrinsic fluorescence of the fructose 1,6-bisphosphate-activated pyruvate kinase from Escherichia coli were investigated in the absence and in the presence of physiological ligands. With respect to the enzyme alone, binding of the allosteric activator fructose 1,6-bisphosphate makes the protein sensitive to tryptic attack and thermolabile, while binding of phosphoenolpyruvate and Mg2+, but not of either ligand separately, induces in the enzyme a highly thermostable conformation, the attainment of which does not require an ordered binding sequence of the two ligands. The apparent loosening of the enzyme structure induced by fructose bisphosphate suggests that the activation it exerts at low phosphoenolpyruvate concentration might be due to an increased accessibility of substrate to the active site. PMID- 1500283 TI - Inhibitory effect of bestatin on the growth of human lymphocytes. AB - Bestatin at mid to high concentration had inhibitory effect to [3H]thymidine incorporation of human lymphocytes. It also decreased the PHA-P, Con A and PWM induced mitogenicity of human lymphocytes. On the contrary, bestatin had growth stimulatory effect to murine lymphocytes, and enhanced the Con A, LPS-induced mitogenicity of murine lymphocytes. These growth inhibitory (human) and stimulatory (mouse) effect of bestatin was found to be independent of adherent cells (macrophage and dendritic cell), indicatory directly working to T or B lymphocytes. PMID- 1500284 TI - A potential vaccine for cocaine abuse prophylaxis. AB - Presently, there are estimated to be 1.5 to 2.0 million individuals infected with HIV-1 in the U.S. and about 12 million worldwide. In the U.S. over 90% of reported cases of AIDS occurred among two subgroups, homosexual males and intravenous substance abusers (IVSAs). Currently, there is no anti-cocaine addiction medication available. In order to explore vaccination as an alternative means for protection against cocaine addition, we immunized inbred male Fisher rats with either cocaine emulsification in complete Freund adjuvant (CFA) or with cocaine conjugated with keyhole limpet hemocyanin (KLH), as carrier plus CFA. Animals were initially immunized with 0.1 mg/animal of cocaine or cocaine-KLH. Animals were given a booster with the corresponding agents after 4 weeks. Ten animals/group were used. Controls received normal saline at the time of immunizations. These animals were injected, intraperitoneally, with 25 mg/kg of cocaine, and were examined for the analgesic effect of cocaine by the hot plate method. The average analgesic effect of cocaine was significantly reduced (p greater than 0.03) in animals immunized with cocaine-KLH (13.77 s) as compared to saline controls (21.6 s). Fifty percent of the animals (5/10) in the cocaine-KLH group and 33% of the animals (3/9) in the cocaine immunized group appeared completely resistant to the effect of cocaine on the central nervous system (CNS). We also have determined the levels of cocaine-specific antibodies produced by each animal by an ELISA method. Degree of protection from cocaine seems to correlate well with the amount of anti-cocaine antibodies produced by each animal (-0.61).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1500285 TI - Augmentation of the radiation-induced antiproliferative effect in combined use of a derivative of nitrosourea, ACNU, with recombinant human tumor necrosis factor. AB - The effect of combined use of a derivative of nitrosourea, ACNU, with recombinant human tumor necrosis factor (rhTNF) on the radiation-induced antiproliferative effect was examined using Meth A tumor cells. The radiation-induced antiproliferative effect was slightly augmented by the simultaneous addition of ACNU at 10 micrograms/ml in 5 Gy and 15 Gy irradiated groups. The antiproliferative effect was augmented in parallel with the radiation dose by the addition of rhTNF. Further augmentation of the proliferation inhibition was observed when both of ACNU (10 micrograms/ml) and 10 U/ml of rhTNF were added in combination with irradiation. Similar augmentation was observed when the target cells were treated with ACNU prior to irradiation and the addition of rhTNF. PMID- 1500286 TI - Inhibition of DNA synthesis in peripheral blood mononuclear cells treated with phosphatidylserines containing unsaturated acyl chains. AB - The immunosuppressive action of phosphatidylserine has been studied in mitogen activated human peripheral blood mononuclear cells. The addition of phospholipid (10-60 nmol/10(6) cells) causes a dose-dependent inhibition of DNA synthesis induced by PHA, anti-CD3 mAb, allogeneic lymphocytes and tetradecanoylphorbol acetate plus ionomycin. In contrast, the interleukin-2-dependent DNA synthesis is less affected. Flow cytometric analysis and binding of radioiodinated interleukin 2 show that the phospholipid prevents the expression of interleukin-2 and transferrin receptors. Removal of monocytes by adherence does not change the action of phosphatidylserine. Furthermore, the phospholipid is equally effective in preparations depleted of CD4+ or CD8+ lymphocytes. Phosphatidylinositol partly reproduces the action of phosphatidylserine. Phosphatidic acid, phosphatidylglycerol and phosphatidylcholine are inactive. Also unsaturated phosphatidylserine analogues inhibit DNA synthesis whereas saturated phosphatidylserines do not. The data suggest that phosphatidylserine mainly affect the steps of T cell activation preceding the production of interleukin-2 and the expression of its receptor. The phosphorylserine headgroup and the unsaturated acyl chains contribute to this effect. PMID- 1500287 TI - Testing the null hypothesis in small area analysis. AB - The goal of small area analysis is often to demonstrate that hospital admission rates or procedure rates vary greatly among regions, suggesting the occurrence of unnecessary admissions or procedures in some regions. Recent articles have shown that such variation may be largely due to chance, even if no underlying differences exist among the small areas; thus, it is important to test if the observed variation is larger than expected by chance. In this article we discuss how the appropriate method for testing the null hypothesis depends on the distribution of the number of admissions at the person level. If it is not possible for an individual to have more than one admission for a given procedure, the appropriate test is a simple chi-square test. If multiple admissions are possible, a modified chi-square test can be used to account for the excess variability due to multiple admissions. Failure to make the correct modification to the chi-square test in this latter case can result in spurious results. This underscores the importance of collecting data on multiple admissions in order to estimate the distribution of the number of admissions at the individual-patient level. PMID- 1500288 TI - Factors affecting interstate use of inpatient care by Medicare beneficiaries. AB - This article examines the extent to which interstate inflow and outflow of patients affects their observed use of Medicare Part A inpatient care. Interstate patient flow can bias utilization rates and may be due to seasonal migration, interstate inpatient care market areas, or purposive seeking of specialized/high quality care. Examination of state level patient flow data drawn from 1987 Medicare discharge indicate that most interstate patient flow occurs between adjacent states probably as an outgrowth of interstate markets. Regression analyses of patient flow data suggest that while seasonal migration is an important determinant of patient flow, its importance is secondary to that of indicators of the availability of specialized services. These findings suggest research questions that may be best answered in detailed analyses of inpatient utilization in interstate market areas and seasonal migration. PMID- 1500289 TI - Evaluation of the HCFA model for the analysis of mortality following hospitalization. AB - From 1987 through 1990, the Health Care Financing Administration (HCFA) evaluated variations in the mortality rates experienced by patients admitted to hospitals participating in the Medicare program. This study was conducted to evaluate the adequacy of the model used for that purpose. Detailed clinical data were gathered on 42,773 patients admitted to 84 statistically selected hospitals. The effect of risk adjustment using the HCFA model, which is based on claims data, was compared to a risk-adjustment model based on physiologic and clinical data. Models that include claims data were markedly superior to those containing only demographic characteristics in predicting the probability of patient death, and the addition of clinical data resulted in further improvement. The correlation of ranks of hospitals based on a model that uses only the claims data and on one that uses, in addition, clinical data, was .91. As a screen for the identification of "high (mortality) outlier" hospitals, the claims model had moderate sensitivity (81 percent) and specificity (79 percent), a high negative predictive value (90 percent), and a low positive predictive value (64 percent) when compared to the clinical model. The two mortality models gave similar results when used to determine which structural characteristics of hospitals were related to mortality rates: hospitals with a higher proportion of registered nurses or board-certified physician specialists, or with a greater level of access to high-technology equipment had lower risk-adjusted mortality rates. These data suggest that the current claims-based risk-adjustment procedure may satisfactorily be used to characterize variations in mortality rates associated with hospitalization. The procedure could also be used as a basis for further epidemiological analyses of factors that affect the probability of patient death. However, it does not positively identify outlier hospitals as providers of problematic care. PMID- 1500290 TI - Determinants of need and unmet need among cancer patients residing at home. AB - De-hospitalization of cancer treatment, particularly for those with advanced disease, can complicate adjustment and strain the capacity of caregiver networks to meet patients' daily needs. Outpatient staff should be able to recognize patients who need help to meet their daily needs as well as those who are not getting enough help. This study describes the physiological and social determinants of need and unmet need for assistance among 629 cancer patients with advanced disease initiating a course of outpatient chemotherapy and/or radiation therapy. Areas of needs examined through telephone interviews with participating patients were: personal care, instrumental tasks (housework, shopping, and cooking), and transportation. Physiological factors (metastases, disease stage, and functional status) were associated with need for assistance in all three areas. Also, older age (over 65) and low income predicted need for help with personal care, and women were more likely than men to report illness-related need for assistance with instrumental tasks and transportation. Unmet need was primarily associated with patients' social support system (e.g., children living nearby and perceived resiliency of network helpers). These findings highlight the need for outpatient staff to evaluate patients' informal care resources as well as patients' symptoms and impairments in deciding who should be referred for home care services. PMID- 1500291 TI - Hospitalization style of physicians in Manitoba: the disturbing lack of logic in medical practice. AB - Variations in hospital admission rates across small areas are ubiquitous, and it is increasingly assumed that high rates result from physicians' discretionary decisions. Data for elderly patients from the health insurance system of Manitoba were used to construct an index that divided physicians into four groups based on their propensity to admit patients to the hospital. I then determined whether physicians who are more prone to admit patients use hospitals for more discretionary purposes and admit patients who are less ill. Although the differences between physicians with different practice styles were in the expected direction, the most compelling finding was the similarity in characteristics of patients admitted by physicians with markedly different practice styles. Such findings suggest a very wide latitude in physicians' decisions to admit patients; this latitude is not well captured by a model that posits a logical relationship between physician treatment patterns and patient need. PMID- 1500292 TI - Change in the Medicare case-mix index in the 1980s and the effect of the prospective payment system. AB - Persistent increases in the Medicare case-mix index over the 1980s have been ascribed to changes both in medical treatment ("real changes") and in the way medical information is recorded ("coding changes") in hospitals. These changes have been attributed, in the absence of appropriate data and analyses, to the incentives of the Medicare prospective payment system (PPS). Using data for 1980 1986 from 235 hospitals, we estimate the effect on the Medicare case-mix index of a series of variables that reflect medical treatments and coding practices. Each of these underlying real or coding variables was changing prior to PPS and would likely have continued to change even in the absence of PPS. Furthermore, PPS may have had a distinct effect on these variables. These underlying trends and the PPS effects must each be estimated. Thus, the analysis begins by developing separate estimates for each of these real and coding variables (1) in the absence of PPS (autonomous effects) and (2) as a result of PPS (induced effects). Then, changes in the case-mix index are regressed against all of these variables to determine the degree to which specific autonomous real or coding variables or induced real or coding variables actually influenced measured case mix. Results show that real and coding changes each accounted for about half of the change in the Medicare case-mix index between 1980 and 1986, with the influence of coding starting to wane by 1986. PPS-induced factors explain about 80 percent of the change in measured case mix over time, autonomous factors about 20 percent. Especially powerful determinants of case-mix change included PPS-induced substitution of surgical for medical care and PPS-induced improvements in the accuracy of coding that led to assignment of patients to higher-weighted DRGs. Also, stringent Medicare peer review organizations appeared to restrain rises in case-mix indexes for their hospitals. Outpatient substitution for inpatient treatment, which others attributed to PPS, was well underway before PPS was announced. PMID- 1500293 TI - Immunocytochemical evidence for the translocation of alpha-granule membrane glycoprotein IIb/IIIa (integrin alpha IIb beta 3) of human platelets to the surface membrane during the release reaction. AB - The localization of glycoprotein (GP) IIb/IIIa (integrin alpha IIb beta 3) in both resting and thrombin-activated platelets was studied immunocytochemically. By the preembedding method where only the GP IIb/IIIa molecules on the surface of platelets were immunostained, the distribution of protein A-colloidal gold label was randomly distributed along the surface membrane of resting platelets at a density of 18.0 +/- 2.7 gold particles/microns of membrane. At 15 s after stimulation by 0.1 U/ml of thrombin in an unstirred platelet suspension, the spheroid-shaped platelets with pseudopodia still had normal numbers of alpha granules, and the density of gold particles was 19.7 +/- 3.6 particles/microns. At 5 min, the alpha-granules were no longer present because of the release reaction, and the density of gold particles significantly increased (27.0 +/- 3.7 particles/microns; p less than 0.01). In immuno-stained ultra-thin frozen sections, the gold particles were detected not only on the surface membrane, including the open canalicular system (OCS), but also on the alpha-granule membranes of resting platelets. At 30 s after thrombin stimulation the alpha granules fused with the OCS, resulting in the formation of a swollen OCS, which still had gold particles on its membrane. At 5 min, the gold particles were detected on the membrane of the swollen OCS located near the surface membrane, while very few gold particles were present on the membrane of the OCS in the central part of the platelets. These results demonstrate that alpha-granule membrane GPIIb/IIIa translocates to the surface membrane through the membrane of the OCS.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1500294 TI - Influence of the decrease of intracellular antigenic content on morphometric analysis: effect of the type and dilution of the first antibody. AB - The aim of the study is to determine the effect degranulation of B cells on their immunohistochemical detection and to evaluate whether this effect depends on the technique of immunological detection. The biological model is the pancreatic insulin-containing B cell. To decrease the insulin content of the pancreas, insulin release was stimulated by five intraperitoneal injections of glibenclamide (2 mg/kg). Specimens of the pancreas were taken for insulin extraction and quantitation by radioimmunoassay (RIA), ultrastructural analyses and immunocytochemistry. The sections were treated either by polyclonal or monoclonal anti-insulin serum at various concentrations and peroxidase antiperoxidase (PAP) technique eventually followed by silver amplification. The B cell insular fraction or relative B-cell area (RBA) was measured with an automatic image analyser. The reference value for the relative B-cell area was established in control rats and corresponds to the ratio of the insular area occupied by immunostained B cells to the islet area. Its value was confirmed by calculation of the area occupied by non-B cells. RIA indicates a decrease of 83% of the insulin content in treated rats while the number of B granules decreases by 72% at the ultrastructural level. In usual conditions (polyclonal serum, 1/1500) the degranulation leads to a 16% underestimation of the B-cell insular fraction. This underestimation increases when monoclonal antibodies are used and further increases when higher dilutions are tested. The silver amplification does not prevent this underestimation and, in this particular model, exclusively acts by increasing the contrast. The only means of restoring the correct level of detection is to use the serum at a higher concentration.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1500295 TI - Sialoglycoderivatives of bovine submandibular gland identified in situ by histochemical techniques combined with lectins. AB - We employed sialidase procedures followed by lectin stainings combined with oxidizing and deacetylating agents to visualize the distribution and sequentiate sialoglycoconjugates in the bovine submandibular gland. In particular we evidenced in acinar and ductal cells the dishomogeneous presence of sialic acids acetylated in the polyhydroxy side chain (C7, C8, C9), whereas O-acetyl substituents at position C1 and/or C4 were not found. Sialoglycoderivatives were also differentiated by the occurrence of penultimate sugars; indeed the dimers sialic acid-(alpha 2----3,6)-beta-galactose and sialic acid-(alpha 2----6)-alpha N-acetylgalactosamine were identified. Using such technique we supported further the possibility to develop methods for the identification of the positions of O acetyl groups and the reconstruction of terminal disaccharides within surface and cytoplasm glycoconjugates. in situ the distribution of different O-acylated sialoglyco-derivatives in the bovine submandibular gland. To this purpose we employed oxydizing and deacetylating agents combined with sialidase digestion and lectin binding. PMID- 1500296 TI - Immunohistochemical co-localization of glycogen phosphorylase with the astroglial markers glial fibrillary acidic protein and S-100 protein in rat brain sections. AB - Immunofluorescence double-labelling and immunoenzyme double-staining methods were used to examine the location of glycogen phosphorylase brain isozyme with the astrocyte markers glial fibrillary acidic protein (GFAP) and S-100 protein in formaldehyde-fixed, paraffin-embedded slices from adult rat brain. Astrocytes in the cerebellum and the hippocampus, which express GFAP or S-100 protein immunoreactivity, show glycogen phosphorylase immunoreactivity. Regional intensity and intracellular distribution of the three antigens vary characteristically. In ependymal cells, glycogen phosphorylase immunoreactivity is co-localized with S-100 protein immunoreactivity, but not with GFAP immunoreactivity. These findings confirm that glycogen phosphorylase in the rat brain is exclusively localized in astrocytes and ependymal cells. All astrocytes, as far as they express GFAP or S-100 protein, do contain glycogen phosphorylase. PMID- 1500297 TI - LR Gold embedding of nervous tissue for immunoelectron microscopy studies. AB - A major drawback of all acrylic resins commonly used for post-embedding immunocytochemical studies of the central nervous system is the disruption of the ultrastructural morphology, due to the high lipid content of neural tissue. We have investigated the suitability of the acrylic resin LR Gold, which has been employed recently for immunogold labeling studies in several non-neural tissues. Optimal preservation of both antigenicity and ultrastructure of nervous tissue was obtained after en bloc staining with uranyl acetate, followed by total dehydration in acetone and curing at low temperature. Cell membranes and myelin sheaths, which are usually lost with other acrylic resins, were well maintained. The degree of antigenicity of LR Gold-embedded tissues was comparable to that of LR White-embedded one, but the morphologic detail was much better preserved. The use of LR Gold is particularly advantageous for studying neurodegenerative disorders such as Alzheimer disease. PMID- 1500298 TI - Quantitative immuno-gold labelling and ultrastructural preservation after cryofixation (combined with different freeze-substitution and embedding protocols) and after chemical fixation and cryosectioning. Analysis of the secretory organelle matrix of Paramecium trichocysts. AB - Among the variety of parameters affecting immuno-gold labelling efficiency, mainly the effects of different preparative protocols were tested. Preservation of ultrastructure and of antigenicity are the salient features of this study. We have labelled insoluble components of the secretory matrix of Paramecium trichocysts with specific antisera, using 10 nm colloidal gold particles. The highest labelling efficiency was obtained with fast freezing (cryofixation, either by sandwich or spray-freezing), freeze-substitution in methanol (without added fixatives) and hydrophilic Lowicryls, particularly when applied at low temperatures (K11M at 193 K). The presence of different chemical fixatives always reduced the labelling density and some recommendations from the literature do not appear advisable. Methods commencing with fixation at greater than or equal to 0 degree C, such as "progressive lowering of temperature" (PLT) or preparation of cryostat sections, i.e. with chemical pretreatments, always resulted in lower labelling density. Our data appear, therefore, relevant for optimal immuno-gold labelling of insoluble antigens and emphasize the potential of cryofixation as a primary preparation step. In addition, ultrastructural preservation was also superior after cryofixation. PMID- 1500301 TI - [Acoustic rhinometry: the bat principle of the nose]. AB - All cross-sectional areas of the upper airway can be measured by an acoustic signal using the acoustic reflection technique, or acoustic rhinometry. The plane of the cross-sectional areas measured was determined in nasal models. The isotemporal layers were found to be nearly parallel to the nasal valve. The acoustically measured cross-sectional areas correlated with the cross-sectional areas of cuts from nasal models. After digitizing these cuts, a CAD software calculates cross-sectional areas in all orientations and at all distances. The difference between the measured and calculated cross-sectional areas is up to 3% in the nasal cavity and up to 17% in the nasopharynx. The hypothesis that the cross-sectional areas measured lie nearly parallel to the nasal valve was confirmed. The normal rhinometric curve shows the minimal cross-sectional area (I notch) to lie at the nasal isthmus. The second narrowest segment of the nasal cavity lies at the head of the inferior concha and septal concha (C-notch). Characteristic examples of patients with turbinate hypertrophy, choanal atresia, enlarged adenoids, and septal deviations are presented. Acoustic rhinometric curves can only be interpreted in combination with the rhinoscopic findings because different pathological conditions can produce similar curves. Recording of reliable and reproducible data by acoustic rhinometry demands that the connection between the rhinometer and the nose does not distort the valve area. When we used two different nose pieces (1.2 and 1.5 cm outer diameter) the cross sectional areas in the anterior third of the nose of only 28% of the patients was measured correctly.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1500299 TI - Ontogeny of glucagon messenger RNA in the rat pancreas. AB - The synthesis of proglucagon mRNA was studied in rat pancreas from day 11 of fetal gestation (E11) to maturity. Proglucagon mRNA was first detected on E11, the time that the pancreatic bud forms in developing rats. The synthesis of proglucagon mRNA and its translation product at this early time point in pancreatic development suggests an early differentiation of A cell function. Between E17 prenatally and day 10-14 postnatally, pancreatic proglucagon mRNA abundance was higher than in adult pancreas. Regulation of the abundance of pancreatic proglucagon mRNA therefore appears to underlie the previously documented increases in serum and pancreatic glucagon immunoreactivity in the late fetal and perinatal periods. By day 20 postnatally, pancreatic proglucagon mRNA declined to levels found in adult pancreas. Prenatally between E17 and E21, changes in proglucagon mRNA abundance did not parallel previously reported developmental changes in relative mass of proglucagon-producing pancreatic A cells. This suggests that changes in proglucagon mRNA abundance during these times may be attributed to changes in proglucagon gene transcription or proglucagon mRNA stability per cell. In contrast between E21 and maturity, changes in proglucagon mRNA abundance paralleled previously reported changes in relative A cell mass, suggesting no major changes in proglucagon gene transcription or mRNA stability per cell during these times. PMID- 1500300 TI - Cytochemical characterization of glycoproteins in the developing acrosome of rats. An ultrastructural study using lectin histochemistry, enzymes and chemical deglycosylation. AB - The composition and distribution of rat acrosomal glycoproteins during spermiogenesis have been investigated at light and electron microscopic level by means of a variety of morphological techniques including the application of lectins conjugated to peroxidase, digoxigenin and colloidal gold, enzyme and chemical deglycosylation procedures and conventional histochemistry. Results obtained with lectin histochemistry in combination with beta-elimination reaction and endoglucosaminidase F/peptide N-glycosidase F digestion suggest that glycoproteins of mature acrosomes contain both N- and O-linked oligosaccharides. N-linked chains of acrosomal glycoproteins contain mannose and external residues of N-acetylglucosamine and galactose. They also have fucose residues linked to the core region of the oligosaccharide side chains. O-linked oligosaccharide chains contain external residues of both galactose and N-acetylgalactosamine. Mannose, fucose, galactose and N-acetylglucosamine residues were detected in acrosomes at all steps of spermiogenesis. N-acetylgalactosamine residues were only observed in the late steps of the spermiogenesis. N-acetylneuraminic acid residues were not detected throughout the acrosomal development. At initial stages of acrosome formation, glycoproteins were preferentially distributed over the acrosomic granules. In cap phase spermatids, lectin binding sites were homogeneously distributed throughout the acrosomes; however, in mature spermatozoa, glycoproteins were predominantly located over the outer acrosomal membrane. PMID- 1500302 TI - [Use of the Nd:YAG laser in otorhinolaryngology]. AB - The Nd:YAG laser is suitable for the treatment of various otorhinolaryngological clinical disorders. These include the palliative reduction of tumor size in sites with difficult access, treatment of hemangiomas and reduction of hyperplastic turbinates. Within certain limits, other indications are treatment of recurrent epistaxis and recurrent polyposis. Palliative reduction of malignancies in the nasopharynx, esophagus, and bronchial system (laser power density: 1500-8000 W/cm2) must sometimes be carried out in several sessions in order to avoid complications due to the laser (i.e., perforation of the bronchial or esophageal wall, lesions of adjacent vessels or nerves). Nd:YAG laser treatment of hemangiomas (500-3000 W/cm2) can lead to excellent results. To avoid excessive thermal lesions, vascular tissue is cooled with ice cubes or with an ice-cold Ringer's solution. The laser process is continued until the onset of tissue blanching. Carbonizations of the tissue are to be avoided. In Nd:YAG laser therapy of hyperplastic lower nasal conchae (approx. 1000 W/cm2), results are based on submucous scarring in which the covering epithelium is maintained. The objective of Nd:YAG laser treatment of recurrent epistaxis in patients with Osler's disease (500 W/cm2) is to reduce the incidence of hemorrhage. Use of the laser in recurrent polyposis is best confined to patients who refuse conventional surgical revision operations. Laser light (500-3500 W/cm2) should only be applied for a short period of time (0.5 s) to avoid creating a rarefying osteitis. PMID- 1500303 TI - [Sonography and plain roentgen image in diagnosis of salivary calculi- experimental studies]. AB - A model was developed in which high-resolution real-time sonography was compared with radiological examinations for determining their sensitivity in diagnosing salivary gland stones. For this purpose an artificial salivary gland medium was compared with human salivary gland tissue for echogenicity. It was shown that both the artificial and the true salivary gland medium possessed comparable acoustic properties. Forty salivary gland stones were examined ultrasonographically in both media with 5 and 7.5 MHz linear scanners and a 5 MHz sector scanner, following which a plain X-ray was done, while 35 of 40 calculi could be definitely identified with linear scanners in both media, this could be accomplished by X-ray only in 50% (20 of 40 calculi). All salivary gland stones greater than 1-2 mm could be detected ultrasonographically, whereas radiological identification did not correlate with stone size. Mineral composition was found to influence the radiological study but not sonographic pictures of sialoliths. If sialolithiasis is suspect clinically, ultrasonography with a linear scanner must be considered the diagnostic procedure of choice. PMID- 1500304 TI - [Esophagotracheal fistula of the cervico-thoracic area--problem solution using a combined trans-cervical and transthoracic approach]. AB - Closure of oesophagotracheal fistulae in the cervicothoracic region using a cervical approach often fails. We report a patient with carcinoma of the larynx who underwent pharyngolaryngectomy, postoperative radiotherapy and several operations for reconstruction of the hypopharynx and cervical oesophagus elsewhere. Finally we were asked to close an oesophagotracheal fistula in the cervicothoracic region. We were successful using a pectoralis major muscle flap via a combined transcervical-transthoracal approach. This interdisciplinary procedure seems to be the method of choice in difficult cases of achieving safe closure of fistulae in this region. PMID- 1500305 TI - [Histocochleographic studies of the late toxicity of cisplatin]. AB - The aim of the investigation was to determine in an animal model the time required for cochlear changes to appear after cisplatin therapy, i.e. whether there is any late ototoxicity detectable. For this purpose we performed histochochleographic studies in the laboratory rat. In two trials different groups of 6-7 rats were given a single daily dose of 2 mg/kg body wt. cisplatin over 5 days. After various periods of time surface preparations of the organ of Corti were performed. The results obtained showed that cochlear damage was evident as early as 4 days after the final injection of drug and no further significant changes in cochlear damage could be seen during the period of observation. PMID- 1500306 TI - [Leiomyosarcoma of the mouth floor and oropharynx]. AB - Leiomyosarcomas arise rarely in the head and neck. We report a 41-year-old woman with an extremely rare leiomyosarcoma of the floor of the mouth extending to the oropharynx. This article stresses the value of imaging methods such as CT, MRI and ultrasound for preoperative diagnosis, and emphasises histopathological findings. The therapeutic principles and prognostic factors of leiomyosarcomas are illustrated on the basis of this case. PMID- 1500308 TI - Treatments for hip dysplasia spark controversy. PMID- 1500307 TI - Cobalamin metabolism. PMID- 1500309 TI - Anderson wins Bustad Award. PMID- 1500310 TI - Food animal veterinarians receive "Purebred" Award. PMID- 1500311 TI - Prominent leprosy research center moves to veterinary school. PMID- 1500312 TI - Wait a minute! PMID- 1500313 TI - It's time to polish our image. PMID- 1500314 TI - Biotechnology and food safety. PMID- 1500315 TI - Moving beyond the rhetoric of food safety and meeting the challenge. PMID- 1500316 TI - New directions for food safety: a USDA perspective. PMID- 1500317 TI - Risk analysis and food safety. PMID- 1500318 TI - The changing face of foodborne disease. PMID- 1500319 TI - Chemical residues in food. PMID- 1500320 TI - The need to establish international standards for foods. PMID- 1500321 TI - The practicing veterinarian's challenge in food safety. PMID- 1500322 TI - Recommendations from the AVMA workshop on the safety of foods of animal origin. PMID- 1500323 TI - Clinical findings in cats with dilated cardiomyopathy and relationship of findings to taurine deficiency. AB - Between October 1986 and September 1988, 37 cats with moderate to severe idiopathic myocardial failure (dilated cardiomyopathy) were evaluated prospectively. Low plasma taurine concentration and diet history including foods that can cause taurine deficiency were documented in most of the cats. Comparison with a retrospectively studied population of 33 cats with dilated cardiomyopathy diagnosed between 1980 and 1986 demonstrated that the clinical and historical findings in the 33 retrospectively studied cats were similar to those in the 37 cats studied prospectively. Clinical findings in the 2 groups were also similar to findings previously reported in the literature. Because clinical findings and diet history were similar in the prospective and retrospective groups, we believe that many cats in the latter group had diet-induced taurine deficiency. These findings support the conclusion that most cases of dilated cardiomyopathy in cats have a common etiopathogenesis related to diet and as such are preventable. PMID- 1500325 TI - Renal transplantation for treatment of end-stage renal failure in cats. AB - Renal transplantation was performed as treatment of end-stage renal failure in 23 cats. Twenty-two cats had chronic renal disease and 1 cat had acute renal disease associated with ethylene glycol-induced toxicosis. Sixteen cats were discharged from the hospital. Nine survived a mean of 8.4 +/- 6.5 months, and 7 cats continue to survive at the time of this report (mean 12.6 months). Seven cats died within 2 weeks of surgery. All renal allografts were obtained from unrelated blood-crossmatch-compatible donors. No deaths were attributable to acute renal allograft rejection, demonstrating the successful maintenance of renal allografts by use of cyclosporine and prednisolone immunosuppression in cats. PMID- 1500324 TI - Response of cats with dilated cardiomyopathy to taurine supplementation. AB - Between October 1986 and September 1988, 37 cats with moderate to severe idiopathic myocardial failure (dilated cardiomyopathy) were evaluated. Clinical management of these cats was similar to that described in the literature, except that it also included administration of 500 or 1,000 mg of the sulfur amino acid, taurine per day. Early death (death within the first 30 days of treatment) occurred in 14 (38%) cats. One cat was lost to follow-up evaluation. Twenty-two cats (59%) had marked clinical and echocardiographic improvement and survived longer than 240 days. In all but 1 cat, the observed improvement in echocardiographic measurements persisted. Hypothermia and thromboembolism were positively associated with an increased risk of early death. Administration of digoxin did not significantly affect survival. All 22 cats that survived greater than 30 days remained clinically stable despite withdrawal of all medications except taurine. Administration of taurine was eventually discontinued in 20 of the 22 cats and adequate taurine intake was thereafter provided for in the food. The clinical response and 1-year survival rate of 58% (21 of 36 cats with a known outcome) in the taurine-treated group represents a marked improvement, compared with a 1-year survival rate of 13% (4 of 31 cats with a known outcome) in a retrospectively evaluated population of 33 cats with dilated cardiomyopathy. PMID- 1500326 TI - Selenium toxicosis in feeder pigs. AB - Selenium toxicosis was diagnosed in feeder pigs on a central Michigan farm. Use of a commercial supplement, found to contain approximately 20 times the intended Se concentration, resulted in a Se concentration of 8.1 mg/kg of the complete feed. This was fed for 34 days during which daily feed consumption decreased approximately 35%, several pigs developed weakness and forelimb paresis, and 1 pig died. The highest serum Se concentration measured was 1,550 ng/ml (normal range, 140 to 190 ng/ml). Normal feed consumption returned when an alternative feed was provided. Mean serum Se concentrations of representative pigs, monitored over the subsequent 26 days, decreased from 905 to 258 ng/ml. Histologic examination of a recovering pig revealed skeletal and cardiac myopathy and bilaterally symmetric malacia of the gray matter of the ventral horns of the spinal cord. During the developing toxicosis, the pigs consumed an estimated 11.4 mg of Se/pig/d. PMID- 1500327 TI - Dioxin intoxication from chronic exposure of horses to pentachlorophenol contaminated wood shavings. AB - Investigations into the cause of health problems on a horse-breeding farm led to the discovery of high concentrations (630 to 9,810 mg/kg of bedding) of pentachlorophenol in wood shavings used as bedding for horses over a period of 2 to 4 years. Toxicologic signs in the horses were characteristic of toxic effects associated with exposure of polychlorinated dibenzo-p-dioxins and dibenzofurans. Tissue residue analysis confirmed presence of toxic polychlorinated dibenzo-p dioxin and dibenzofuran isomers known to be in pentachlorophenol, substantiating the bioavailability of polychlorinated dibenzo-p-dioxins and dibenzofurans in the wood shavings. The findings provide evidence that residue concentrations in the range of 2 ng/g of toxic polychlorinated dibenzo-p-dioxin isomers in liver or fat correlate with toxicologic effects in horses. PMID- 1500328 TI - Heterotopic salivary tissue in a weanling colt. AB - Heterotopic salivary tissue was diagnosed in a 7-month-old Quarter Horse colt with a history of a draining wound in the left temporal region from time of birth. Surgical excision of the tract was performed for diagnosis and treatment. Histologically, tissues were compatible with a mixed-type salivary gland, most likely of parotid salivary gland origin. Complete resolution of the drainage was achieved after surgical removal of the ectopic tissue. PMID- 1500329 TI - Ultrasonographic evaluation and surgical treatment of humeral osteitis and bicipital tenosynovitis in a horse. AB - Ultrasonography and radiography were used to diagnose bicipital tenosynovitis and humeral osteitis in a horse with a history of lameness of 7 weeks' duration. Surgical exploration confirmed the diagnosis. PMID- 1500330 TI - Immunodeficiency associated with lymphosarcoma in a horse. AB - Immune system dysfunction and immunoglobulin deficiency was diagnosed in a 2-year old horse with disseminated lymphosarcoma. Prolonged (35 days) parenteral nutrition was delivered to support the horse during a period in which immune function studies could be performed. Correction of nutritional compromise by use of parenteral nutrition did not correct the immunoglobulin deficiency, and results of lymphocyte phenotype testing did not indicate abnormal proportions of leukocytes. Lymphoblast transformation studies were suggestive of a circulating immunosuppressive factor in the horse's serum. Normal cell function was detected when the cells were stimulated in precolostral equine serum. PMID- 1500331 TI - Multicentric cutaneous pythiosis in a foal. AB - A 5-month-old male Quarter Horse was examined because of multicentric, granulomatous, cutaneous lesions of the dorsum and prepuce. The cutaneous lesions were excised, and sodium iodide was administered orally for 2 weeks. Multicentric cutaneous pythiosis was diagnosed by histologic examination and immunoperoxidase staining of excised tissues. By 3 months after surgery, all lesions had healed. PMID- 1500332 TI - Idiopathic granulomatous disease with ocular adnexal and cutaneous involvement in a dog. AB - Idiopathic granulomatous disease was the cause of bilateral eyelid masses and additional ocular adnexal disease in a dog. Histologically similar granulomas developed concurrently in distant sites including the limbs, prepuce, and testicles. Periodic resolution and redevelopment of the masses were observed and were unaffected by corticosteroid treatments. Rapid diminution of some of the masses was found after treatment with polyethylene glycol modified L asparaginase, but poor client compliance and episodes of spontaneous resolution of some of the masses made it difficult to accurately assess effectiveness of treatment. Clinicians should be aware that ocular adnexal granulomas may simulate neoplasms and be a component of a more widespread disease process. PMID- 1500333 TI - Severe bilateral fibrosing pleuritis associated with chronic chylothorax in five cats and two dogs. AB - Severe bilateral fibrosing pleuritis was diagnosed in 5 cats and 2 dogs with chronic chylothorax. All animals were dyspneic on initial examination and remained moderately to severely dyspneic after thoracentesis. Radiographic evidence of fibrosing pleuritis included rounded lung lobes and failure of the lungs to reexpand following effective pleural drainage. Fibrosing pleuritis was also suggested in several animals with radiographic evidence of pleural fluid, in which pleural fluid could not be retrieved. Macroscopically, the lung lobes of all animals were compressed and atelectatic to various degrees, and the pleura appeared to be diffusely thickened and roughened. In several animals, fibrous adhesions were found between the parietal and visceral pleura of some lobes. Lung lobes were markedly constricted and appeared as small, smooth, rounded hilar masses in 4 animals. Mild to moderate pulmonary edema was evident in 3 animals at necropsy. Six of the 7 animals died (2) or were euthanatized (4) within 72 hours after the diagnosis of fibrosing pleuritis. The fibrosing pleuritis developed in 1 animal with lymphoblastic lymphosarcoma and chylothorax after treatment via passive pleuroperitoneal drainage; this animal was euthanatized because of underlying neoplasia. One cat, in which decortication was performed and resulted in marked reexpansion of the lung lobes, died 4 hours after surgery with signs compatible with pulmonary edema. On the basis of our findings, we suggest that animals with chronic chylothorax are at risk to develop fibrosing pleuritis. Furthermore, animals with severe bilateral fibrosing pleuritis should be given extremely guarded prognoses. PMID- 1500334 TI - Paraphimosis in a teaser bull with penile translocation. AB - A bull with penile translocation and bilateral caudal epididymectomy developed paraphimosis when used for estrus detection of cows. The paraphimosis did not resolve with bandaging and topical treatment; thus, it was surgically corrected by retracting the distal sigmoid flexure of the penis and suturing it to the superficial fascia in the medial femoral region. Paraphimosis should be considered a possible sequela to penile translocation in bulls. PMID- 1500335 TI - Chronic frontal sinusitis in dairy cattle: 12 cases (1978-1989). AB - Chronic frontal sinusitis in 12 dairy cattle most often was associated with a history of dehorning, in which the sinus was entered (67%), or with respiratory tract disease (25%). The most common organisms isolated were Actinomyces pyogenes and Pasteurella multocida. Signs of infection did not develop for months in some cattle and were often intermittent. The most common clinical signs included anorexia, lethargy, fever, frontal bone distortion, exophthalmos, abnormal posture, nasal discharge, and neurologic abnormalities. Treatment consisted of trephination at 2 sites, drainage and lavage of the sinus cavity, and administration of antibiotics and analgesics. Eight cattle responded well to treatment and were discharged, but 4 others had signs of CNS involvement and died or were euthanatized. Trephination of the frontal sinus cavity at carefully chosen sites and antibiotic treatment are indicated when sinusitis is suspected. Drainage of the sinus cavity is imperative to avoid extension of the infection into the CNS. PMID- 1500336 TI - Surgical treatment of colic in American miniature horses: 15 cases (1980-1987). AB - A study of 15 American miniature horses (AMH) that underwent surgical treatment for colic was performed. Information obtained from the medical records included signalment, clinical signs, type and location of gastrointestinal lesion, and postoperative complications. All 15 AMH had intraluminal obstructions, attributable to feed impactions (11 horses), enteroliths (2), and sand (2). The most common location of obstruction was the small colon, which was involved in 9 of the 15 cases. All 15 AMH survived and were discharged from the hospital. Six of the 15 AMH underwent subsequent surgical treatment for abdominal disorders. Elapsed time between the first and second operations ranged from 1 month to 5 years. Intestinal adhesions were observed in all AMH that were surgically treated twice. Thus, despite the fact that most of the AMH had a simple intraluminal obstruction, 40% (n = 6) developed adhesions that required or complicated a second surgery. Of the 15 AMH, 87% (n = 13) survived at least 12 months after the initial exploratory celiotomy. These findings suggest that most surgical abdominal conditions in AMH can be corrected; however, precautions should be taken to avoid or minimize adhesion formation. PMID- 1500337 TI - Dorsomedial articular fracture of the proximal aspect of the third metacarpal bone in standardbred racehorses: seven cases (1978-1990). AB - Seven Standardbred horses, all pacers, with a mean age of 2.9 years (range, 2 to 4 years), had dorsomedial articular fracture of the proximal aspect of the third metacarpal bone. Fracture caused acute, unilateral, severe lameness after training or racing. Lameness was abolished by midcarpal joint anesthesia in 4 horses. Six horses had a palpable bony swelling, which caused signs of pain. Radiography revealed a nondisplaced, articular, oblique fracture extending distad toward the dorsomedial cortex for a mean distance of 28 mm (range, 15 to 40 mm). In all horses, chronic periosteal proliferative changes, seen near the distal aspect of the fracture, corresponded to palpable bony exostoses and were associated with the medial attachment of the extensor carpi radialis tendon. In 1 horse, internal fixation followed by a 6-month rest resulted in a successful outcome. All other horses were given 3 months' rest without surgery and were not lame. Five horses raced successfully and lowered the lifetime race records, 1 horse was sound and trained successfully, but died of colic, and 1 horse was not lame in early training. PMID- 1500338 TI - What is your diagnosis? Panosteitis. PMID- 1500339 TI - Chemical modification of antibiotic streptonigrin; synthesis and properties of 2' decarboxy-2'-aminostreptonigrin (streptonigrone-2'-imine). PMID- 1500340 TI - Production of new anthracycline antibiotic betaclamycin B by microbial conversion with a specific aclacinomycin-negative mutant. PMID- 1500341 TI - Studies on the biosynthesis of fosfomycin. 3. Detection of phosphoenol-pyruvate phosphomutase activity in a fosfomycin high-producing strain of Streptomyces wedmorensis and characterization of its blocked mutant NP-7. PMID- 1500342 TI - Isolation and characterization of sporeamicin C. PMID- 1500343 TI - Amides of antibiotic streptonigrin and amino dicarboxylic acids or aminosugars. Synthesis and biological evaluation. PMID- 1500344 TI - Calcium signal modulators inhibit aerial mycelium formation in Streptomyces alboniger. PMID- 1500345 TI - Isolation and characterization of new peptide antibiotics, plusbacins A1-A4 and B1-B4. AB - New antibiotics, plusbacins A1-A4 and B1-B4, were isolated from the culture broth of a strain of Pseudomonas sp. These antibiotics were isolated as a complex by column chromatographies on Diaion HP-20 and silica gel, and then separated by HPLC. They are amphoteric in nature. The hydrochlorides are obtained as colorless powders, soluble in methanol and alkaline water. From their physico-chemical properties, these antibiotics are presumed to be acyloctapeptides containing a lactone linkage, and their differences occur in amino acid and fatty acid residues. The antibiotics are active against Gram-positive bacteria in vitro and in vivo. PMID- 1500346 TI - Structures of new peptide antibiotics, plusbacins A1-A4 and B1-B4. AB - The constituent amino acids of plusbacins A1-A4 were determined to be two moles of L-trans-3-hydroxyproline and one mole each of D-threo-beta-hydroxyaspartic acid, L-threo-beta-hydroxyaspartic acid, D-allo-threonine, D-serine, D-alanine and L-arginine. In plusbacins B1-B4, one mole of L-trans-3-hydroxyproline is replaced by L-proline. The fatty acid residue of A1 and B1 was determined to be 3 hydroxy-tetradecanoic acid, for A2 and B2 to be 3-hydroxy-isopentadecanoic acid, for A3 and B3 to be 3-hydroxy-isohexadecanoic acid, and for A4 and B4 to be 3 hydroxy-hexadecanoic acid. A lactone linkage was suggested to reside between L threo-beta-hydroxyaspartic acid and 3-hydroxy-fatty acid residues by degradation experiments. The amino acid sequences of plusbacins A2 and B2 were confirmed by Edman degradation of their deacylated products, and supported by mass spectrometric studies. From the above, structures of all components of plusbacins were concluded. PMID- 1500347 TI - Mersacidin, a new antibiotic from Bacillus. Fermentation, isolation, purification and chemical characterization. AB - Mersacidin (1) is a new peptide antibiotic containing beta-methyllanthionine. It is classified as a member of the proposed lantibiotic group of antibiotics, and is produced by a species of Bacillus. Mersacidin has a molecular weight of 1,824 (C80H120N20O21S4). The antibiotic is active against Gram-positive organisms including methicillin-resistant Staphylococcus aureus, but has no activity against Gram-negative bacteria or fungi. PMID- 1500348 TI - Mersacidin, a new antibiotic from Bacillus. In vitro and in vivo antibacterial activity. AB - Mersacidin is a new peptide antibiotic of the proposed lantibiotic family. It is active in vitro and in vivo against Gram-positive bacteria including the methicillin-resistant Staphylococci. Its in vitro activity is less than those of vancomycin and erythromycin but it shows much higher activity in the in vivo system than can be expected from the in vitro testing results. A water soluble potassium salt has been prepared which has an activity profile similar to that of mersacidin, but has better in vivo activity against Streptococcus pyogenes than the parent compound. PMID- 1500349 TI - SF2457, a new antibiotic related to amicetin. AB - A novel nucleoside antibiotic, SF2457, was isolated from the fermentation broth of Nocardia brasiliensis SF2457. The structure of SF2457 was determined by degradation studies using alkaline hydrolysis and methanolysis. SF2457 is closely related to the amicetin group antibiotics. The antibiotic exhibited inhibitory activity against Gram-positive and Gram-negative bacteria. PMID- 1500350 TI - Production and biological activities of a new antifungal antibiotic, TAN-950 A. AB - A novel antifungal antibiotic, TAN-950 complex, was isolated from the culture filtrate of Streptomyces platensis A-136 (IFO 14603, FERM BP-1786). The water soluble amphoteric substances in this complex were purified by chromatography using ion-exchange resins, QAE-Sephadex and adsorptive resins and were designated TAN-950 A and TAN-950 A-E mixture. The molecular formula of TAN-950 A was determined to be C6H7N2O4Na for the sodium salt. This new amino acid antibiotic showed antifungal activity against Candida albicans in vitro and in vivo, and had low toxicity in mice. PMID- 1500351 TI - Sphingofungins A, B, C, and D; a new family of antifungal agents. I. Fermentation, isolation, and biological activity. AB - In screening for antifungal inhibitors from fungi, four related antifungal agents have been isolated from the cultivation of Aspergillus fumigatus ATCC 20857. These agents were initially produced by the microorganism growing on a solid millet-based medium. A liquid medium containing both glucose and glycerol has also been developed in which these antibiotics are produced in two phases. These novel compounds, sphingofungins A, B, C, and D, show a limited spectrum of antifungal activity but were especially effective against Cryptococcus species. PMID- 1500352 TI - A new macrocyclic lactam antibiotic, BE-14106. I. Taxonomy, isolation, biological activity and structural elucidation. PMID- 1500353 TI - A new antitumor antibiotic product, demethylchartreusin. Isolation and biological activities. AB - A new antitumor antibiotic, 3''-demethylchartreusin was isolated from the culture broth of Streptomyces chartreusis, as a minor component of crude chartreusin. It is structurally related to chartreusin, containing same aglycone of chartreusin, but different sugar moieties. 3''-Demethylchartreusin exhibits some potent inhibitory activities against murine tumors. PMID- 1500354 TI - Depudecin: a novel compound inducing the flat phenotype of NIH3T3 cells doubly transformed by ras- and src-oncogene, produced by Alternaria brassicicola. AB - A novel compound depudecin inducing the flat phenotype of ras- and src- transformed NIH3T3 cells at a concentration of 1 microgram/ml was isolated from the culture broth of Alternaria brassicicola. Based on its spectroscopic characteristics and X-ray crystallographic analysis of its bis-(1S)-(-) camphanate, the structure of depudecin was determined to be (2R,3S,4S,5E,7S,8S,9R)-2,9- dihydroxy-3,4;7,8-diepoxy-undeca-5,10-diene. PMID- 1500355 TI - Adipostatins A and B, new inhibitors of glycerol-3-phosphate dehydrogenase. AB - As a result of screening for inhibitors of glycerol-3-phosphate dehydrogenase, which may be effective to prevent corpulence, we isolated two inhibitors named adipostatin A and adipostatin B from the culture broth of Streptomyces cyaneus 2299-SV1. Their structures have been established to be 5-n-pentadecylresorcinol and 5-isopentadecylresorcinol, respectively. Adipostatin A and adipostatin B inhibited glycerol-3-phosphate dehydrogenase at the IC50 values of 4.1 microM and 4.5 microM, respectively. These compounds prevented triglyceride accumulation in 3T3-L1 cells at a concentration of the microM level. PMID- 1500356 TI - PI-200 and PI-201, new platelet aggregation inhibitors produced by Streptomyces sp. A7498. Taxonomy, fermentation, isolation, physico-chemical properties, structure determination and biological properties. AB - Two new platelet aggregation inhibitors, PI-200 and PI-201 were isolated from the fermentation broth of Streptomyces sp. A7498. PI-200 and PI-201 inhibited ADP induced aggregation of rabbit platelets with an IC50 of 3.8 x 10(-4) M and 7.1 x 10(-4) M, respectively. PMID- 1500357 TI - Leualacin, a novel calcium blocker from Hapsidospora irregularis. I. Taxonomy, fermentation, isolation, physico-chemical and biological properties. AB - A new calcium blocker, designated leualacin, has been isolated from Hapsidospora irregularis. The compound inhibits the binding of 3H-nitrendipine, a well known synthetic calcium blocker, to cardiac Ca channel in a competitive manner, although its structure is completely different from dihydropyridines. PMID- 1500358 TI - Leualacin, a novel calcium blocker from Hapsidospora irregularis. II. Structure determination. PMID- 1500359 TI - Herboxidiene, a new herbicidal substance from Streptomyces chromofuscus A7847. Taxonomy, fermentation, isolation, physico-chemical and biological properties. AB - Screening of microbial fermentation broths for herbicidal activity led to the discovery of a novel polyketide, herboxidiene, from an actinomycete identified as a member of the Streptomyces chromofuscus cluster. A 14- to 20-fold increase in fermentation production of herboxidiene was achieved as a result of media optimization. Herboxidiene was purified using successive reverse phase C18 steps and Sephadex LH-20 chromatography. Its molecular formula, C25H42O6, was determined by HRFAB-MS. Herboxidiene demonstrated exceptionally potent, selective, herbicidal activity against a variety of weed species and was inactive against wheat, even at rates as high as 5.6 kg/hectare. PMID- 1500360 TI - RU 29 246, the active compound of the cephalosporin prodrug-ester HR 916. III. Pharmacokinetic properties and antibacterial activity in vivo. AB - The pharmacokinetics of the broad spectrum cephem RU 29 246 and its prodrug-ester HR 916 B were investigated in mice, rats and dogs and compared to those of cefpodoxime proxetil, cefuroxime axetil and cefixime. HR 916 B is well absorbed following oral administration and efficiently converted to the antibacterially active form. In mice, mean peak blood levels of 31.1 micrograms/ml of the parent compound were recorded within 20 minutes after oral administration of a single dose equivalent to 40 mg/kg RU 29 246. The bioavailability calculated on the basis of the areas under the concentration-time curves (AUC) and the urinary recoveries was about 90%. In rats, peak blood levels of 14.5 micrograms/ml were obtained 1 hour after an oral 20 mg/kg dose. The bioavailability was calculated as 70%. In dogs, 40% of an oral 10 mg/kg dose was recovered in the urine within 24 hours. Cmax was 15.9 micrograms/ml at 4.6 hours. Mean elimination half-lives of RU 29 246 were 0.35, 0.5 and 2.1 hours in mice, rats and dogs, respectively. After an oral HR 916 B dose equivalent to 50 mg/kg of RU 29 246, tissue concentrations at 0.5 hour ranged between 0.8 micrograms/g in brain and 95.7 micrograms/g in murine kidneys. These values of HR 916 B are similar to, or distinctly higher than, those of the reference compounds. Of the oral cephalosporins tested, HR 916 B had the most balanced antibacterial spectrum. With ED50s of between 0.9 and 11.5 mg/kg against staphylococci, its activity was similar to that of the additional reference compound cefaclor and higher than that of cefuroxime. Cefixime and cefpodoxime proxetil displayed low antistaphylococcal activity or were inactive. In septicemias with Enterobacteriaceae, cefixime and cefpodoxime proxetil were more potent than HR 916 B and cefaclor. Cefuroxime axetil was inactive against most of these infections. HR 916 B was also highly effective against murine lung infections caused by Klebsiella pneumoniae DT-S or Streptococcus pneumoniae 1147. PMID- 1500361 TI - Studies on cephalosporin antibiotics. V. Synthesis, antibacterial activity and oral absorption of new 3-[(Z)-2-methoxycarbonylvinylthio]-7 beta- [(Z)-2-(2 aminothiazol-4-yl)-2-(oxyimino)acetamido]cephalosporins. AB - A series of new 3-[(Z)-2-methoxycarbonylvinylthio]-7 beta-[(2- aminothiazol-4 yl)acetamido]-cephalosporins (1) having various oxyimino groups (Z-form) at the alpha position of the C-7 side chain was synthesized and evaluated for antibacterial activity and oral absorption in rats. Of these, the cephalosporin (1a) with a hydroxyimino group in the C-7 side chain showed a potent antibacterial activity against Gram-negative bacteria and Gram-positive Staphylococcus aureus as well as good oral absorption in rats. The structure activity relationships of 1 are also presented. PMID- 1500362 TI - Synthesis and in vitro activity of novel quaternary ammonium carbapenems: 2 pyridiniopropyl and 1-pyridinioethyl carbapenems. AB - The synthesis of new carbapenems having either a pyridiniopropyl group at the 2 position or a pyridinioethyl group at the 1-position is described, along with the preparation of their corresponding hydroxy and acetoxy analogs. The antibacterial activity, susceptibility to dehydropeptidase-I (DHP-I) enzyme and chemical stability of these new carbapenems are also reported. 2-Pyridiniopropyl carbapenem 4 was found to possess excellent antibacterial activity. It was more stable chemically and less susceptible to the DHP-I enzyme than the thio analog 3. 1-Pyridinioethylcarbapenem 5 showed significantly reduced antibacterial activity as compared to 2-pyridiniopropylcarbapenem 4. PMID- 1500363 TI - Totally synthetic analogues of siastatin B. I. Optically active 2 acetamidopiperidine derivatives. AB - Totally synthetic analogues of siastatin B, optically active 2-acetamido-3,4,5 trihydroxypiperidines having the nitromethyl, aminomethyl and carboxyl branched groups at C-5 have been obtained from D-ribono-1,4-lactone by a stereospecific convergent method. Some analogues showed inhibitory activity against some glycosidases. PMID- 1500364 TI - Totally synthetic analogues of siastatin B. II. Optically active piperidine derivatives having trifluoroacetamide and hydroxyacetamide groups at C-2. AB - Siastatin B analogues, optically active 2-(trifluoroacetamide)- 3,4,5 trihydroxypiperidines having nitromethyl, aminomethyl and carboxyl branched groups at C-5, and (+)-(2R,3R,4R,5R)-5-(aminomethyl)-3,4,5-trihydroxy-2- (hydroxyacetamido)piperidine have been obtained total synthetically from D-ribono 1,4-lactone. Some analogues have inhibitory activity against some glycosidases, and (+)-(2R,3R,4R,5R)-2-(trifluoroacetamido)-3,4,5-trihydroxypiperi dine-5 carboxylic acid showed a marked inhibitory activity against beta-glucuronidase. PMID- 1500365 TI - Synthesis and biological properties of 1 beta-methylcarbapenems with N methylpyrrolidinylthio group at C-2 position. AB - A series of 1 beta-methylcarbapenem compounds, which have a 5'-substituted-N methylpyrrolidin-3'-ylthio group as a C-2 side chain, have been prepared and their biological properties were investigated. Substitution with a methyl group on the nitrogen atom in the C-2 side chain effectively enhanced stability to renal dehydropeptidase-I as well as introduction of methylene spacer between the aminocarbonyl group and the pyrrolidine ring of the 5'-aminocarbonylpyrrolidin-3' ylthio group. PMID- 1500366 TI - Anthelmintic activity of dioxapyrrolomycin. AB - Dioxapyrrolomycin, pyrrolomycin C, pyrrolomycin D, and piericidin C2 produced by UC 11065 were evaluated as anthelmintics. Assays used to examine these compounds included effects on the free-living nematode Caenorhabditis elegans, ability to clear target nematodes (Haemonchus contortus and Trichostrongylus colubriformis) from jirds, and clearance of Haemonchus contortus from lambs. A crude extract of UC 11065 containing dioxapyrrolomycin, pyrrolomycin C, pyrrolomycin D, and piericidin C2 was active against C. elegans and against H. contortus in the jird. Purified and/or synthetic samples of dioxapyrrolomycin, pyrrolomycin C, pyrrolomycin D, and piericidin C2 were tested in the jird model; only dioxapyrrolomycin exhibited appreciable activity against H. contortus (greater than or equal to 90.9% clearance at 0.33 mg/jird), while none of the compounds showed appreciable activity against T. colubriformis. Dioxapyrrolomycin cleared 99.9% of H. contortus from lambs at 12.5 mg/kg. An in vitro migration study using susceptible and closantel-resistant H. contortus showed there is cross-resistance between dioxapyrrolomycin and closantel. Dioxapyrrolomycin appears to be a narrow spectrum anthelmintic which works through a closantel-like mode-of-action. PMID- 1500367 TI - Neomycin biosynthesis: the incorporation of D-6-deoxy-glucose derivatives and variously labelled glucose into the 2-deoxystreptamine ring. Postulated involvement of 2-deoxyinosose synthase in the biosynthesis. AB - D-[6-3H3]6-Deoxy-5-ketoglucose (10) and D-[5,6-3H2]6-deoxyglucose (11) were incorporated into neomycins B and C using a growing culture of Streptomyces fradiae. D-[6-3H]6-Deoxy-5-ketoglucose was incorporated into neomycin, as efficiently as the well established precursor D-glucose, and was found to label exclusively the 2-deoxystreptamine ring of the antibiotic. The results strengthened the previous proposals that in the formation of 2-deoxystreptamine the C-6 hydroxyl group of D-glucose is removed prior to the cyclisation reaction. Studies using the incorporation of D-[3-3H]glucose, D-[3,4-3H2]glucose and D-[5 3H]glucose into neomycin followed by the degradation of the latter established that in the biosynthesis of the 2-deoxystreptamine ring the C-4 and C-5 hydrogen atoms of glucose are removed. The loss of the C-4 hydrogen atom of the glucose is attributed to the formation of a 4-keto derivative which facilitates the removal of the C-5 hydrogen atom thus setting the stage for the expulsion of the C-6 hydroxyl group. The 5,6-olefinic intermediate formed in the process then undergoes cyclisation eventually releasing 2-deoxyinosose. The enzyme systems which participate in the conversion of D-glucose equivalent into 2-deoxyinosose may be described as 2-deoxyinosose synthase that in broad mechanistic terms resembles dehydroquinate synthase. PMID- 1500368 TI - SO-75R1, a new mutactimycin derivative produced by Nocardia brasiliensis. PMID- 1500369 TI - Synthesis of geometrical isomers of 3-(3-acetoxy and 3-carbamoyloxy-1-propenyl) cephalosporins and their structure-activity relationships. PMID- 1500370 TI - Two-tone suppression in inner hair cell responses: correlates of rate suppression in the auditory nerve. AB - Inner hair cell (IHC) recordings were made from second turn of the guinea pig cochlea where characteristic frequencies are approximately 4000 Hz. In order to compare IHC responses with rate suppression measured in the auditory nerve, suppressors were introduced that produced little or no response in the hair cell. The effects of a variable-frequency suppressor on a constant-frequency probe, placed near characteristic frequency, were also investigated since this paradigm is commonly used in single unit experiments. Resulting magnitude changes were measured in the fundamental component of the ac receptor potential and/or in the total dc produced in the region of temporal overlap between the two stimulus inputs. This latter component is especially important when considering how changes in IHC responses relate to decreases in discharge rate in single auditory nerve fibers. Since the ac receptor potential is filtered by the hair cell's basolateral membrane, the dc component probably controls transmitter release at the characteristic frequency of these second-turn IHCs. Based on results from these and previous experiments, a proposal is advanced to explain the evolution of two-tone suppression in the peripheral auditory system. The paper also discusses the use of excitatory versus non-excitatory suppressors and includes a description of two-tone suppression areas at the mechanical, IHC and single unit levels. The explanation of low-side suppression areas is of special interest since hitherto they have been difficult to model (Kim, 1985). PMID- 1500371 TI - Metabolic labelling and quantitation of proteins synthesized by single chick cochleas. AB - Molecular studies of the peripheral auditory system are made difficult by the small quantities of tissue available and by their relative inaccessibility. In addition, the cochlea and other hair cell-containing receptor organs are composed of both hair cells and supporting cells, as well as several other cell types. The identification of known proteins and the characterization of specific and novel protein molecules from these tissues require the use of sensitive techniques and a consideration of the complex histology. The chick cochlea was selected as an experimental system since the cochlea is relatively accessible in the bird, the receptor neuroepithelium contains a large number of hair cells compacted in a small area, and the physiology of the auditory periphery has been studied extensively. A general procedure is described for the metabolic radiolabelling of proteins from single cochleas followed by their solubilization, separation by high-resolution two-dimensional gel electrophoresis, and accurate quantitation. The method is highly reproducible and sensitive, and should prove useful in studies of proteins from the specialized cell types of the chick cochlea, including the identification of those whose rates of synthesis are modified in response to acoustic stimulation and sound damage or recovery. PMID- 1500372 TI - Cochlear efferent neurons projecting to both ears in the chicken, Gallus domesticus. AB - Different retrograde neuroanatomical tracers were injected into each cochlea of adult chicken. The number of cells labeled in the cochlear efferent cell group found bilaterally within the caudal pontine reticular formation depended upon the tracer, with True Blue and Fluoro Gold yielding maximal average counts of 332 efferent neurons per injection. Double labeling of less than 1% of these cells was possible with the combination of True Blue and Diamidino Yellow. Thus the contribution of efferent neurons with axon collaterals projecting to both ears is not fundamentally different in birds and other vertebrates. PMID- 1500373 TI - C-type potassium channels in the lateral cell membrane of guinea-pig outer hair cells. AB - The basolateral cell membrane of outer hair cells (OHC) from the mammalian cochlea is known to contain K(+)-channels. The prevailing type, a high conductance K(+)-channel was further characterized in the present study in order to support its classification as C channel. OHC were isolated from the 3rd and 4th turn of the guinea-pig cochlea. Cell-attached and excised inside-out patches of the lateral cell membrane were investigated. The C-type channel had a selectivity for K+ over Na+ of 12:1 to 20:1 and displayed Goldman-type rectification and voltage-dependence of the open probability. The kinetics of both opening and closing could be described by time constants in the range of ms. The channel provides a calcium- and voltage-activated pathway through OHC lateral membranes for passive K+ transport. PMID- 1500374 TI - Low-frequency modulation of compound action potential in experimental perilymphatic fistula and endolymphatic hydrops. AB - We have tested the hypothesis that the cause of cochlear dysfunction associated with perilymphatic fistula (PLF) is closely related to endolymphatic hydrops (ELH). Using guinea pigs, we studied the tone-burst elicited compound action potential (CAP) and its modulation as caused by a 50 Hz biasing tone in experimental PLF. We compared these results with those of experimental ELH. Following perilymph aspiration through the perforated round window membrane, mild but significant elevations of CAP thresholds at tested frequencies were found. A reduction in the amplitude of cochlear microphonics (CM) for a 50 Hz sine wave appeared to correlate with these CAP threshold changes. However, there were no significant changes in the modulation effect of the 50 Hz biasing tone on the CAP elicited by an 8 kHz tone burst. This finding differed from that in ears with experimental ELH, in which significant reductions of both 50 Hz CM and the degree of CAP modulation were consistently observed. We concluded that it is unlikely that the underlying mechanisms of a modification to the low frequency response of the base of the cochlea following perilymph aspiration is linked to that of experimental ELH. PMID- 1500375 TI - Morphology of HRP-labelled cochlear nerve axons in the dorsal cochlear nucleus of the developing hamster. AB - To study the development of the central terminal arbors of the cochlear nerve fibers in the dorsal cochlear nucleus, horseradish peroxidase-labelled axons in young and adult hamsters were analyzed morphometrically. Brainstem slices with whole cochlear nuclei were maintained in a slice chamber and the cochlear nerve root was injected with a mixture of wheat germ agglutinin-horseradish peroxidase, horseradish peroxidase and poly-L-ornithine. The poly-L-ornithine was added to keep the injection site small; small injections resulted in only a few axons being labelled and permitted reconstruction of individual fibers. Axons underwent an initial period of ingrowth that was completed prior to the onset of hearing (postnatal day 16). After this time the morphology and area of influence of the axons remained unchanged but the nucleus continued to increase in size. Since no additional cochlear nerve axons grow into the nucleus during this period of nuclear growth, the existing axons necessarily become more widely spaced as development proceeds. These anatomical changes may contribute to the progressive narrowing of auditory cell tuning curves. PMID- 1500376 TI - Quantitative carbohydrate analyses of the tectorial and otoconial membranes of the guinea pig. AB - Carbohydrate composition of the tectorial membrane (TM) and the otoconial membrane (OM) of the guinea pig was analyzed after hydrolysis, using high performance anion-exchange chromatography and pulsed amperometric detection. Both of the tissues were highly glycosylated; the carbohydrate content being 24-42% of protein. GlcN, Gal, Glc and Man were found to be the major component sugars of TM, whereas little GalN was found. Fuc and NANA were also present, but NGNA was not detectable. After digestion with thermolysin for solubilization, OM was separated into two fractions: insoluble mineral particles of the otoconia (OM ppt) and a soluble fraction from the gelatinous layer (OM-sup). These two fractions showed distinct carbohydrate composition from each other. Further analyses using glycosidases revealed that TM contained asialyl and monosialyl but little di-, tri- and tetrasialyl N-glycosides, and OM-sup did not seem to be susceptible to endo-beta-galactosidase, which is known to cleave some N-acetyl polylactosamine and keratan sulfate. Based on these analyses, it can be suggested that most of the carbohydrates in TM are likely to be asialyl and monosialyl N glycosides. N-Glycosides may be predominant in the otoconia as well, and a polymer structure consisting of GlcN(Ac) and Gal other than N-acetyl polylactosamine may exist in the gelatinous layer of OM. O-Glycosylation of the usual type appeared to be minor in all the fractions. PMID- 1500377 TI - Comparisons of the development of auditory brainstem response latencies between cats and humans. AB - Developmental changes in the peak latencies of auditory brainstem responses (ABR) recorded from humans and kittens were compared to test the hypothesis that developmental time courses among mammals are the same when appropriately normalized. Response latencies were computed as the difference from adult latency and conceptional ages were represented as percentages relative to the age that ABR wave latencies achieved a criterion value within 0.2 ms of asymptotic latency (i.e., adulthood). An underlying assumption of this exercise is that far-field response latency is an appropriate index of overall 'auditory development'. Results of this analysis suggest that developmental changes in latency of responses arising within the auditory periphery are similar between humans and cats, when appropriately normalized, and that more central changes show less correspondence. Consequently, absolute time course differences for specific developmental parameters must be considered and caution should be exercised when extrapolating results acquired from one species to the other. PMID- 1500378 TI - Rate and frequency interactions in the auditory brainstem response of the adult rat. AB - Tone pip stimuli were used at different repetition rates to examine influences upon auditory brainstem response components. Rate increases to 80.1/s result in significant latency increases in waves IV and V at all test frequencies. Rate effects occur in rostral brainstem response components which show frequency related latencies different from wave I. Amplitude measures decline at higher repetition rates for waves I and IV at most test frequencies. Rate effects are most pronounced at 8 kHz stimulation which is around the optimal behavioral frequency in rat. At higher rates the second peak of wave I is enhanced at 8 kHz, whereas the third peak of wave I at 40 kHz disappears. These results demonstrate that tone-specific stimuli provide sensitive measures of latency, amplitude and wave morphology of components of the auditory brainstem response as a function of stimulus repetition. PMID- 1500379 TI - Distribution of F-actin and fodrin in the hair cells of the guinea pig cochlea as revealed by confocal fluorescence microscopy. AB - We double-stained paraformaldehyde fixed guinea pig cochleas with rhodaminated phalloidin to detect F-actin and with a monoclonal antibody against non-erythroid spectrin (fodrin). The hair cells were studied in surface specimens of the organ of Corti with confocal fluorescence microscopy. In serial optical sections, phalloidin stained the stereocilia, cuticular plate, and a circumferential ring beneath it in the inner and outer hair cells (IHCs and OHCs). The cytoplasm of the IHCs and the OHCs was unlabelled, but the infracuticular network of the OHCs in the upper turns showed a strong reaction. The lateral plasma membrane was unreactive with phalloidin in the IHCs and OHCs, except in the basal turn, where a moderate reaction, probably representing actin of Deiter's cups, was seen along the lateral walls of the basal pole of the OHCs. Fodrin was similarly seen in the cuticular plate, in a circumferential ring beneath it, and in the infracuticular network of the apical OHCs. The most interesting finding was the fodrin-specific distinct labelling of the lateral cell surface in the OHCs of the basal cochlear turn. This staining diminished towards the apex and was practically absent in the OHCs located above the level of 15 mm from the round window. The lateral cell surface of IHCs showed moderate fodrin labelling in all cochlear turns. This staining was much weaker than that seen in the basal OHCs. Fodrin labelling revealed deformation from the regular cylindrical shape in midportion of the OHC bodies in the basal turn of the cochlea. PMID- 1500381 TI - Single visit endodontics. PMID- 1500380 TI - Forward and reverse transduction at the limit of sensitivity studied by correlating electrical and mechanical fluctuations in frog saccular hair cells. AB - The spontaneous fluctuations of the intracellular voltage and the position of the sensory hairbundle were measured concurrently using intracellular microelectrodes and an optical differential micro interferometer. Magnitude and frequency distribution of the hair bundles' spontaneous motion suggest that it consists mostly of Brownian motion. The electrical noise, however, exceeds the value expected for thermal Johnson noise by several orders of magnitude, and its frequency distribution reflects the transduction tuning properties of the hair cells. Frequently, a strong correlation was observed between the fluctuations of the hair bundle position and the intracellular electrical noise. From the properties of the correlation and from experiments involving mechanical stimulation we conclude that in most cases mechano-electrical transduction of the bundles' Brownian motion causes this correlation. Small signal transduction sensitivities ranged from 18 to 500 microV/nm. Bundle motion that was observed in response to current injection in more than half of the cells suggests the existence of a fast reverse (electro-mechanical) transduction mechanism to be common in these cells. The sensitivities could be as high as 600 pm of bundle deflection per millivolt of membrane potential change. In a significant minority (4 in 44) of cells, all showing excess electrical noise, we found 'non-causal' components of the electro-mechanical correlation, and in two of those cells narrow-band bundle motion in excess of their thermal motion at frequencies coincident with peaks in the intracellular noise was observed. PMID- 1500382 TI - The epidemiology of ovarian cancer. AB - The epidemiologic data collected to date have provided some important and provocative clues as to the etiology of ovarian cancer. The recognition of familial clustering of this disease has led to exciting advances in understanding the genetics involved. The contribution of endocrine factors has been well documented in the epidemiologic literature, leading to important insights into the process of carcinogenesis. Clearly, additional information is needed to further explain the interplay of genetic, physiologic, and life style factors, to lead to a better understanding of the disease, and ultimately to a means of prevention and control. PMID- 1500383 TI - Ovarian cancer. PMID- 1500384 TI - Pathology of epithelial tumors. AB - The pathology of epithelial tumors is reviewed in this article, with particular emphasis on new information. Important new data of prognostic significance concerning tumors in the borderline group are emphasized, and the division of mucinous borderline tumors into two groups is discussed. Serous carcinomas of surface type are reviewed, which have recently been the subject of a great deal of study, as well as transitional cell carcinoma, a newly defined subtype of invasive cancer. Finally, the highly aggressive small cell carcinoma is briefly discussed. PMID- 1500385 TI - Prognostic factors in ovarian cancer. AB - Epithelial ovarian cancers vary considerably in their biologic behavior and this is reflected in the variety of clinicopathologic factors that are used for predicting outcome. This article assesses the potential value of some of the newer prognostic factors and critically evaluates the more commonly used clinicopathologic variables. PMID- 1500386 TI - Hereditary ovarian carcinoma. AB - No woman is at greater risk for ovarian carcinoma than one who is a member of a hereditary ovarian carcinoma syndrome kindred and whose mother, sister, or daughter has been affected with this disease and with an integrally related hereditary syndrome cancer. This article surveys the existing understanding about hereditary ovarian carcinoma. Emphasis is given to its diagnosis, heterogeneity, interpretation, and the application of this information to improving cancer control. PMID- 1500387 TI - Oncogenes in ovarian cancer. AB - The discovery of cancer-causing genes has provided us with the exciting opportunity to begin to understand the molecular pathology of ovarian cancer. Activation of several of these genes including HER-2/neu, myc, ras, and p53 has been described in some ovarian cancers (Table 2). In addition, some proto oncogenes such as the EGF receptor (erbB) and the M-CSF receptor (fms) are expressed along with their respective ligands in some ovarian cancers. Finally, for every oncogene that has been studied in ovarian cancer, there are at least a half-dozen that remain unexplored. In the future, when we have a better understanding of the molecular pathology involved in the development of ovarian cancer, this may allow us to better diagnose and treat, and eventually prevent, ovarian cancer. PMID- 1500388 TI - Growth regulation of ovarian cancer. AB - The disease referred to as ovarian cancer is composed of those tumors derived from the ovarian surface epithelium. Ovarian cancer incidence peaks in postmenopausal women, when the hormonal milieu is in a state of flux. The ovarian carcinomas have histologic characteristics of classical endocrine responsive tissues. For example, the serous tumors are similar in appearance to the epithelium of the fallopian tube, the mucinous tumors to that of the endocervix, and the endometrioid tumors to that of the endometrium. These observations alone suggest a role for hormones in disease etiology and progression. In addition, much experimental evidence has accumulated that shows direct hormonal and growth factor effects on the normal and neoplastic ovarian surface epithelium and the potential for responsiveness based on the presence of specific receptors. The concept that growth stimulatory substances, by their impact on mitosis and cell number, may influence the rate of mutations that could confer malignant transformation serves as an additional mechanism by which growth stimulatory substances can influence ovarian cancer initiation. With the emergence of new molecular biology techniques, future studies should unravel the mechanisms by which steroid hormones, peptide hormones, and peptide growth factors influence the development of ovarian cancer. PMID- 1500389 TI - Ovarian cancer. Early diagnosis and screening. AB - Late diagnosis is the main reason for the poor outcome of ovarian cancer patients. An attempt to diagnose the disease methods for early diagnosis was recently investigated. The main effort of the study was in finding the role of ultrasonography and CA-125 and their sensitivity and specificity in the screening procedure. The preliminary reports suggest that a mortality study with a large women population has to be done before the usefulness of screening these methods can be established. PMID- 1500390 TI - Management of early-stage ovarian cancer. AB - Approximately 30% of patients with epithelial ovarian cancer present with localized or early-stage disease. Accuracy of staging is dependent on careful surgical staging. Subsets of patients with specific prognostic factors have now been identified who do not require additional therapy after proper primary surgical staging. Poor prognosis patients do require adjuvant therapy. Whole abdominal irradiation, intraperitoneal P32, and single agent and combination chemotherapy have been utilized. The optimal therapy or whether any therapy is truly effective remains unknown. PMID- 1500391 TI - Chemotherapy for advanced epithelial ovarian cancer. AB - In the past decade there have been significant improvements in chemotherapy for advanced ovarian cancer. Platinum-based chemotherapy has improved response rates and, to a lesser degree, prolonged survival. Taxol and its combination with platinum drugs holds the promise for even further improvements in survival. Clinical trials are evaluating issues such as dose-intensity, new combinations, and drug resistance. PMID- 1500392 TI - The current role of radiotherapy in the management of ovarian cancer. AB - The role of radiation in the management of ovarian carcinoma continues to be a controversial issue. This article discusses some of the controversies surrounding treatment with radiotherapy in the context of an analysis of the reasons that have led to the apparent failure of radiotherapy to cure many patients and describes several new experimental strategies with a potential for future improvement. Although the recent outcome of the combined modality approach has been extremely frustrating, the prospects for future developments of the experimental leads described in this article are encouraging and will hopefully translate into more effective results of this approach in ovarian carcinoma. PMID- 1500393 TI - Intraperitoneal therapy in the management of patients with ovarian cancer. AB - Basic pharmacologic principles support the concept that more drugs can be delivered to the tumor when it is delivered through the intraperitoneal route. Pharmacokinetic studies have confirmed that for many chemotherapeutic agents a substantial pharmacologic advantage can be achieved using this approach. Preliminary studies have suggested that intraperitoneal chemotherapy may be especially advantageous in patients with small-volume disease or in patients who have a negative second-look laparotomy. Clinical studies are ongoing to further define the role intraperitoneal therapy will play in the management of patients with ovarian cancer. PMID- 1500394 TI - Ovarian cancer. Experimental chemotherapy. AB - Ovarian cancer is a drug-sensitive disease, yet most patients still succumb after initial response. Experimental approaches to this disease include the discovery of new drugs, including taxol and ifosfamide; evaluation of candidate drugs such as tetraplatin and topotecan; and approaches to overcome intrinsic and/or acquired resistance. The latter has been addressed by increasing dose-intensity of currently available therapy, developing agents to abrogate dose-limiting toxicity, and by attempts to interfere with mechanisms of resistance. PMID- 1500395 TI - Biologic and immunologic therapy of ovarian cancer. AB - Conventional cytotoxic chemotherapy fails to cure the majority of patients with advanced-stage ovarian cancer, in spite of encouraging initial antitumor responses. With the emergence of drug resistance in refractory tumors, new biologic and immunologic treatment strategies are needed. Small-volume residual peritoneal disease remains an attractive target for therapeutic trials; however, even in this optimal circumstance, few regimens have yet achieved a high frequency of pathologically confirmed complete remissions. Considerable progress has been made in understanding the impact of growth factors and their receptors on tumor growth regulation and modulation of response to chemotherapy. Better characterization of the antigens recognized by monoclonal antibodies, as well as sequencing of the antibodies themselves, has permitted the rational design of therapeutic reagents that take full advantage of molecular biology techniques for production and conjugation. Important limitations of preclinical models for prediction of host toxicity are recognized, and the reasons for treatment failure in situ, as well as strategies to prevent serious dose-limiting toxicities, are being explored. Further developments in cytokine biology, adoptive cellular therapy, monoclonal antibody conjugation, and molecular biology will continue to provide a growing array of reagents for critical evaluation. PMID- 1500396 TI - Pulse wave mechanics revisited: relevance to therapy of cardiovascular disease with calcium antagonists. PMID- 1500397 TI - Epinephrine and calcium have similar oxygen costs of contractility. AB - We compared the oxygen cost of increasing ventricular contractility using Emax (slope of the ventricular end-systolic pressure-volume relation) as the index of ventricular contractility. Contractility was enhanced by calcium and epinephrine in paired experiments on dog left ventricles. Firstly, we obtained left ventricular oxygen consumption (VO2) and systolic pressure-volume area (PVA, a measure of total mechanical energy) of contractions at different volumes in the control contractile state to determine a reference VO2-PVA relation. PVA was obtained as the area in the pressure-volume (P-V) diagram which was bounded by the end-systolic P-V line, end-diastolic P-V curve and systolic P-V trajectory of individual contractions. Secondly, we gradually enhanced Emax with calcium and epinephrine in two consecutive runs at a fixed ventricular volume. Both VO2 and PVA increased with enhanced Emax. From these VO2-PVA data, we calculated the PVA independent VO2 values at the respective enhanced Emax levels and determined the oxygen cost of Emax as the slope of the relation between the PVA-independent VO2 and Emax. The cost per beat and per 100 g was 0.00158 ml O2/(mmHg/ml) for calcium and 0.00166 ml O2/(mmHg/ml) for epinephrine on average, values not significantly different from each other (P less than 0.05). We conclude that epinephrine and calcium have similar oxygen costs of contractility over a wide range of Emax despite their different pharmacological mechanisms of positive inotropism. PMID- 1500398 TI - Effect of flosequinan on exercise capacity and cardiac function in patients with chronic mild heart failure: a double-blind placebo-controlled study. AB - Although beneficial effects of a new vasodilating agent, flosequinan, have been demonstrated in patients with severe heart failure, its efficacy has not been studied in patients with a less severe form of chronic heart failure. In this study, the effects of 4 weeks' administration of flosequinan, 50 mg daily, and placebo on exercise capacity, cardiac function, and symptoms of heart failure were investigated in 24 patients with chronic mild heart failure (New York Heart Association functional class, mainly class II) in a double-blind clinical trial. When the parameter changes during the treatment period of the flosequinan and placebo groups were compared, no significant difference was found in any of the measurements except for left ventricular fractional shortening determined from M mode echocardiograms; it was increased by 2.9 +/- 1.3% in the flosequinan group whereas it was decreased by 1.3 +/- 0.9% in the placebo group (P less than 0.05 vs flosequinan treatment). However, when compared to baseline values, flosequinan significantly increased exercise time in the symptom-limited maximal exercise test (704 +/- 103 to 763 +/- 107 s, P less than 0.05) and the oxygen uptake at the anaerobic threshold (13.8 +/- 1.3 to 16.7 +/- 1.4 ml/min kg, P less than 0.05), and improved symptoms assessed with a new heart failure severity classification (a median value of 2.0-1.5, P less than 0.05). These improvements were not observed in the placebo group. Serious adverse effects were not observed in either group. These results suggest that flosequinan is useful for the treatment of chronic mild heart failure as well as severe heart failure. PMID- 1500399 TI - Reverse redistribution on Tl-201 SPECT images after reperfusion therapy for acute myocardial infarction: possible mechanism and prognostic implications. AB - So-called reverse redistribution on stress Tl-201 imaging has been reported previously, but its significance and clinical implications are not well understood. In patients who received reperfusion therapy for acute myocardial infarction, we frequently observed reverse redistribution on stress Tl-201 images. To investigate the significance of reverse redistribution, 61 patients who underwent reperfusion within 4 h of the onset of chest pain underwent submaximal exercise Tl-201 imaging 3 weeks later. We performed simultaneous coronary arteriography and left ventriculography. We divided these 61 patients into three groups based on the pattern of Tl-201 images. Reverse redistribution was found in 19 patients (Group A), 12 patients had redistribution (Group B), and 30 patients had nonreversible defects (Group C). All patients in Group A had less residual stenosis than those in the other groups, and showed significant improvement of left ventricular function. Furthermore, 12 patients (Group A) demonstrated reverse redistribution or a normal pattern in a follow-up study performed 12 months later. However, in the delayed images the defect was smaller than that shown in the previous study. None of the patients had any symptoms and all returned to their previous occupations. In conclusion, reverse redistribution was common in patients undergoing reperfusion therapy for acute myocardial infarction, especially those with little residual stenosis. Reverse redistribution appears to indicate improved regional wall function in such patients. PMID- 1500400 TI - Morphological and functional study of free arterial grafts. AB - Morphological and functional changes of free arterial grafts in dogs were studied for 3 weeks after implantation and the changes were compared to those in implanted free vein grafts. In the arterial grafts, endothelial cells with abundant pinocytotic vesicles and some cytoplasmic folds were observed by transmission and scanning electron microscope and cell detachment was seen only at the site of anastomosis, while most cells were detached in the vein grafts. The site of mechanical damage in the arterial grafts was covered by regenerated endothelial cells which showed similar morphological findings to the normal arterial endothelial cells. In contrast, regenerated cells in the vein grafts started to cover the denuded area 7 days after the implantation and had completely covered it by 3 weeks. Prostacyclin was produced more abundantly in arterial grafts than in vein grafts at any phase after implantation. The level of prostacyclin production was between 30 and 40 pg/mg in any phase after implantation of free arterial grafts, while in vein grafts the level was 2.5 pg/mg at the day of implantation and increased to 13.6 pg/mg at 21 days. This study showed that the endothelial cells were well preserved and the level of prostacyclin production was high in the arterial grafts, and thus the grafts seemed to show potent anti-thrombogenicity after implantation. Although late changes in arterial and vein grafts were not investigated in this experimental protocol, these results may suggest that the arterial graft is superior to the vein graft even in the early period after its implantation as a free graft. PMID- 1500401 TI - Papillary fibroelastoma in the left ventricular outflow tract. AB - We report a case of a papillary fibroelastoma originating from the left ventricular endocardium in the outflow tract which was discovered by echocardiography in an asymptomatic patient. Two echocardiographic features were observed: (1) the tumor surface was smooth, and characteristic papillary formation was not detected; and (2) the outline of the mass was clearly defined as a dense echo, with the central, radiolucent, portion surrounded by a highly refractive linear echo at the level of the maximum diameter of the mass. The excised tumor was covered with a gelatinous substance that masked multiple papillae on the surface, but its echolucent center could not be explained by the pathology of the tumor which was solid centrally. Our case indicates that a papillary fibroelastoma may sometimes show echocardiographic findings similar to those of a myxoma, although other investigators have not noted the smooth surface and the echolucent center makes it indistinguishable from a myxoma. Thus, in some cases, it is difficult to distinguish papillary fibroelastoma from myxoma by echocardiography. PMID- 1500402 TI - If not now, when? PMID- 1500403 TI - Poor response to fluoxetine: underlying depression, serotonergic overstimulation, or a "therapeutic window"? AB - BACKGROUND: Symptoms of serotonergic overstimulation may resemble depressive symptoms. Postulating that overmedication with fluoxetine can appear as response failure (as norfluoxetine accumulates), systematic trials of lower doses were conducted in patients who failed to respond despite apparent initial improvements. METHOD: Of 23 consecutive outpatients treated with fluoxetine 20 mg/day for DSM-III-R major depression, 4 failed to sustain initial improvements during 4-8 weeks of treatment (in the absence of apparent side effects). In these 4 patients, fluoxetine was withdrawn for 2 weeks, then reinstituted at 20 mg q.o.d. All patients were followed up weekly to monthly (for up to 17 months) and administered the 17-item Hamilton Rating Scale for Depression. RESULTS: Four of 4 patients improved during washout and went on to respond to the lower dose. All 4 cases are presented. On review of the literature, fluoxetine fixed-dose studies reveal increased adverse effects with no increase in efficacy at dosages above 5 mg/day and decreased efficacy at dosages above 40 mg/day. Special issues inherent in the study and use of an antidepressant with a 1- to 3-week active half-life are discussed. CONCLUSION: Even in the apparent absence of side effects, nonresponse to fluoxetine may be due to overmedication in some patients. Standard doses of fluoxetine may be higher than "optimum." The apparent difficulty distinguishing fluoxetine's adverse effects/toxicity (or a "therapeutic window" effect) from underlying depressive symptoms, taken in conjunction with the 3-9 weeks required to approach steady state, may suggest the option of lowering the dose in some cases of nonresponse or "relapse." PMID- 1500404 TI - Does fluoxetine exacerbate Parkinson's disease? AB - BACKGROUND: Because fluoxetine may be associated with an induction or exacerbation of parkinsonism, caution has been suggested when considering fluoxetine as an antidepressant for patients with Parkinson's disease. METHOD: We retrospectively reviewed the medical records of 23 outpatients with Parkinson's disease who were receiving or had received fluoxetine. One author evaluated all patients using the Northwestern University Disability Scale for scoring parkinsonism. Rather than employing a formal depression scale, we assessed depression globally. Concurrent medications were permitted. RESULTS: Twenty of the 23 patients experienced no worsening of parkinsonism while being treated with up to 40 mg of fluoxetine per day. The other 3 patients' parkinsonism worsened to a mild degree: a 74-year-old man experienced an increase in akinesia, tremor, and rigidity; a 77-year-old man experienced a slight worsening in tremor and rigidity; and a 56-year-old man experienced a decline in gait and akinesia. It was unclear if these declines, which were neither acute nor severe, were due to fluoxetine treatment or the progression of the disease. Signs of parkinsonism in 2 patients appeared to improve during fluoxetine treatment. CONCLUSION: Fluoxetine, in doses up to 40 mg/day, does not appear to be associated with exacerbations of parkinsonian signs and symptoms in outpatients with Parkinson's disease. Further investigation of fluoxetine for the treatment of depression in patients with Parkinson's disease is warranted. PMID- 1500405 TI - DSM-III-R brief reactive psychosis among Air Force recruits. AB - BACKGROUND: Clinical characteristics of patients diagnosed with brief reactive psychosis based on DSM-III-R criteria and the incidence of this disorder in a defined population have not been sufficiently studied. Some military recruits who are subjected to relatively uniform levels of stress in a monitored environment over a specified time period develop transient, severe psychotic symptoms consistent with a diagnosis of brief reactive psychosis. METHOD: We retrospectively reviewed all cases of brief reactive psychosis that occurred among 139,360 Air Force recruits during 6-week basic training experiences over a 3-year period. Brief case descriptions, including clinical courses, are provided. RESULTS: Six cases were found among 557 consecutive psychiatric admissions between January 1, 1988, and January 1, 1991 (annual incidence = 1.43 cases per 100,000 recruits). An apparent temporal relationship was found between the onset of the stressor (basic military training) and the development of psychosis. Paranoid symptomatology, including persecutory delusions, was present in all cases. Adjustment disorders were the most common diagnoses in patients admitted from the training environment (N = 464). CONCLUSION: Brief reactive psychosis is a rare discharge diagnosis in this large population of young Air Force recruits. Prospective studies are warranted to evaluate the usefulness of DSM-III-R criteria for this disorder and to determine the longitudinal course of patients who have received this diagnosis. PMID- 1500406 TI - Premenstrual exacerbation of depression: one process or two? AB - BACKGROUND: Premenstrual symptoms occur in the setting of other psychiatric disorders, particularly affective disorders. The nosologic issue of whether premenstrual syndrome is an entity distinct from other psychiatric disorders is controversial. METHOD: We review the association between depression and premenstrual syndrome and describe symptoms in a small series of patients (N = 5) with premenstrual syndrome both during and after resolution of major depression. RESULTS: The overall symptom severity decreased after antidepressant treatment, but this decrease was only significant for dysphoria. In two subjects, other cyclical symptoms consistent with premenstrual syndrome became more apparent after treatment of major depression, possibly because background symptoms of depression improved. CONCLUSION: Premenstrual symptoms, including dysphoric changes and irritability, can continue despite effective treatment of major depression. PMID- 1500407 TI - Dexamethasone for the treatment of depression. PMID- 1500408 TI - HIV-related psychosis. PMID- 1500409 TI - NMS and lethal catatonia. PMID- 1500410 TI - Fluoxetine treatment of slow eating. PMID- 1500411 TI - Pathogenesis of chronic fatigue syndrome. PMID- 1500412 TI - Establishment of anti-human cholesteryl ester transfer protein monoclonal antibodies and radioimmunoassaying of the level of cholesteryl ester transfer protein in human plasma. AB - Plasma cholesteryl ester transfer protein (CETP) facilitates the net transfer and exchange of cholesteryl ester (CE), triglyceride (TG), and phospholipids between lipoproteins. A series of monoclonal antibodies (mAbs) against human CETP was obtained, comprising mAbs either inhibiting or not inhibiting these transfer activities. One mAb (LT-J1) inhibited the transfer activity of TG almost completely, but not that of CE, indicating that CE and TG binding sites on the CETP molecule may be distinct from each other, and that this mAb may specifically recognize the TG binding site. A radioimmunoassay system for determining the level of CETP was also established using these mAbs, and the plasma CETP levels in 20 normolipemic Japanese adults were found to range from 2.1 to 2.7 mg/liter. PMID- 1500413 TI - Resonance Raman study on complexes of medium-chain acyl-CoA dehydrogenase. AB - Resonance Raman (RR) spectra of the complex of pig kidney medium-chain acyl-CoA dehydrogenase with acetoacetyl-CoA and of the purple complex formed upon the addition of octanoyl-CoA to the dehydrogenase were obtained. RR spectra were also measured for the complexes prepared by using isotopically labeled compounds, i.e., [3-13C]-, [1,3-13C]-, and [2,4-13C2]acetoacetyl-CoA; [1-13C]octanoyl-CoA; the dehydrogenase reconstituted with [4a-13C]- and [4,10a-13C2]FAD. Both bands of oxidized flavin and acetoacetyl-CoA were resonance-enhanced in the 632.8 nm excited spectra of the acetoacetyl-CoA complex; this confirms that the broad long wavelength absorption band is a charge-transfer absorption band between oxidized flavin and acetoacetyl-CoA. The 1,622 cm-1 band was assigned to the C(3)=O stretching mode coupling with the C(2)-H bending mode of the enolate form of acetoacetyl-CoA and the bands at 1,483 and 1,119 cm-1 were assigned to bands associated with the C(2)=C(1)-O- moiety. Both bands of fully reduced flavin and the substrate were resonance-enhanced in the 632.8 nm excited spectra of the purple complex. As the enzyme is already reduced, the substrate must be oxidized to octenoyl-CoA; the complex is a charge-transfer complex between the reduced enzyme and octenoyl-CoA. The low frequency value of the 1,577 cm-1 band, which is associated with the C(2)-C(1)=O moiety of the octenoyl-CoA, suggests that the enzyme-bound octenoyl-CoA has an appreciable contribution of C(2)=C(1)-O .(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1500414 TI - A novel ceramide trihexoside from the eggs of the sea urchin, Hemicentrotus pulcherrimus. AB - Glucosylceramide (Glc beta 1-1Cer) and a novel ceramide trihexoside (Gal beta 1 6Gal beta 1-6Glc beta 1-1Cer) were purified from the eggs of the sea urchin, Hemicentrotus pulcherrimus. Their chemical structures were determined by gas liquid chromatography, methylation analysis, chromic acid oxidation, enzymatic hydrolysis, enzyme-linked immunosorbent assay, fast atom bombardment mass spectrometry, and proton nuclear magnetic resonance spectroscopy. The ceramide trihexoside has a novel carbohydrate structure, and its core structure, Gal beta 1-6Glc, is also novel. The ceramide moieties of these glycolipids are almost identical. Two fatty acids, 22:1 and 22h:1, constitute more than 80% of the total acids. Long-chain bases are all phytosphingosine, approximately 90% of which is n t18:0. The finding of melibiosylceramide (Gal alpha 1-6Glc beta 1-1Cer) from the eggs of another sea urchin species [Kubo, H. et al. (1988) J. Biochem. 104, 755 760] and the present finding of the novel ceramide trihexoside suggest that there are a variety of unique sugar structures in sea urchin glycosphingolipids. PMID- 1500415 TI - Structure-activity relationship in buffalo spleen cathepsin B. AB - Effect of pH, urea, and guanidine hydrochloride on the activity and structure of buffalo spleen cathepsin B was investigated. At alkaline pH, there was an irreversible loss of the structure as well as the activity of the buffalo enzyme. At acidic pH, however, the inactivation of the enzyme was reversible. The enzyme reversibly lost most of its activity at denaturant concentrations which did not cause a significant change in its secondary structure. The inactivation could be attributed to minor perturbations in the environment of the amino acid residue(s) at and/or around the active site of the enzyme. High urea/guanidine hydrochloride concentrations leading to the structural changes in cathepsin B made the inactivation process irreversible. PMID- 1500416 TI - Developmental and liver-specific expression directed by the serum amyloid P component promoter in transgenic mice. AB - Transgenic mice were produced by microinjection of a human serum amyloid P component (hSAP) gene or a fusion gene (SS) comprising the promoter for hSAP (nucleotides -600 to -14 from the start codon) and the coding region of the hepatitis B virus surface antigen (HBsAg). In adult mice, both transgenes were expressed only in the liver, and thus the pattern of expression resembled that of the endogenous mouse SAP gene. Both hSAP mRNA and HBsAg were first detected in liver on the second postnatal day. The level of these products increased rapidly and reached the maximum within the first week. These results suggest that the hSAP gene contains a short, cis-acting, developmental, and liver-specific regulatory sequence at the 5' or the 3' end and that this sequence can target expression of the foreign gene. PMID- 1500417 TI - Purification and characterization of an 85 kDa sialoglycoprotein in rat liver lysosomal membranes. AB - Sialoglycoprotein with a molecular mass of 85 kDa (LGP85) was purified from rat liver lysosomal membranes with a 0.9% recovery to apparent homogeneity, as determined from the pattern on polyacrylamide gel electrophoresis in the presence and in the absence of SDS. The purification procedures included: preparation of lysosomal membranes, elimination of LGP107 and LGP96 with immunoaffinity columns, WGA-Sepharose affinity chromatography, hydroxylapatite chromatography, and preparative polyacrylamide gel electrophoresis. LGP85 contains about 22.8% carbohydrate and the carbohydrate moiety is composed of mannose, galactose, fucose, glucosamine, galactosamine, and neuraminic acid, in a molar ratio of 40:20:2:23:3:13. Susceptibility to neuraminidase and immunoreactivity of the protein in intact tritosomes were examined to study the topology of the protein in tritosomal membranes. Neuraminidase susceptibility and immunoreactivity of the protein were not observed in intact tritosomes until the tritosomes had been disrupted by osmotic shock. These observations suggest that both oligosaccharide chains and the main protein portion of the protein are located on the interior surface of the tritosomal membranes. Subcellular localization of LGP85 was determined using enzyme immunoassay. The lysosomes seem to be the major location. LGP85 in the lysosomes was divided into the membrane bound form (90%) and the soluble form (10%). Immunoelectron microscopy clearly confirmed that the localization of LGP85 is mainly confined to lysosomes. PMID- 1500418 TI - Calcium-induced splitting of connectin filaments into beta-connectin and a 1,200 kDa subfragment. AB - When rabbit skeletal muscle myofibrils were treated with a solution containing 0.1 mM Ca2+ and 30 micrograms of leupeptin/ml, alpha-connectin, which forms very thin filaments in myofibrils, was split into beta-connectin and a 1,200-kDa subfragment. A part of beta-connectin located near the junction between beta connectin and the subfragment seems to have an affinity for calcium ions and to be susceptible to the binding of large amounts of calcium ions. The calcium binding site on beta-connectin is localized near the N2 line in the I band, and the subfragment is localized adjacent to the Z disk. It is possible that connectin filaments change their elasticity during the contraction-relaxation cycle of skeletal muscle at the physiological concentration of calcium ions. Because postmortem skeletal muscles lose their elasticity and become plastic in association with the calcium-specific splitting of connectin filaments, the splitting is considered to be a factor in meat tenderization during postrigor ageing. PMID- 1500419 TI - Beta-oxidation of butyrate, the short-chain-length fatty acid, occurs in peroxisomes in the yeast Candida tropicalis. AB - When an n-alkane-utilizable yeast, Candida tropicalis pK233, was cultivated on butyrate, the fatty acid of shortest chain-length for beta-oxidation, as the sole source of carbon and energy, catalase and the enzymes of the fatty acid beta oxidation system were inducibly synthesized at high levels. As in the alkane grown cells, the proliferation of peroxisomes was harmonized with the induction of peroxisomal enzymes. The results of subcellular fractionation and immunoelectronmicroscopy indicated the localization of these enzymes in peroxisomes, not in mitochondria. It was suggested that only peroxisomes have a role in fatty acid beta-oxidation in the yeast cells, unlike in mammalian cells, in which cooperation between peroxisomes and mitochondria is essential. PMID- 1500420 TI - Phosphorylation of histone H2A by protein kinase C and identification of the phosphorylation site. AB - In regenerating rat liver, nuclear protein histone H2A was shown to be phosphorylated on its amino-terminal serine residue [Sung et al. (1971) J. Biol. Chem. 246, 1358-1364], but the protein kinase which phosphorylates this residue has not been identified. To evaluate the possibility that protein kinase C can phosphorylate this residue, calf thymus histone H2A was 32P-labeled by incubation with [gamma-32P]ATP and highly purified protein kinase C from rat brain in the presence of calcium and phospholipid. About 1 mol of 32P was incorporated per mol of histone H2A and the Km and apparent Vmax of the reaction were calculated to be 2.1 microM and 0.35 mumol/min/mg, respectively. So histone H2A seemed to be a good substrate for protein kinase C. Further, the proteolytic phosphopeptides of 32P-labeled histone H2A were isolated by means of a series of column chromatographies and analyzed for their amino acid compositions. Comparison of the data with the known primary structure of histone H2A revealed their amino acid sequence as 1Ser-Gly-Arg. These data suggest that protein kinase C may be a candidate for the protein kinase which phosphorylates the amino-terminal serine residue of histone H2A during the regeneration of rat liver. PMID- 1500421 TI - Studies on amino acid sequences of two isoforms of 17-kDa essential light chain of smooth muscle myosin from porcine aorta media. AB - Amino acid sequences were analyzed for two isoforms of myosin essential light chain, LC17a and LC17b [Hasegawa, Y., Ueno, H., Horie, K., & Morita, F. (1988) J. Biochem. 103, 15-18] from porcine aorta smooth muscle. Both LC17a and LC17b consisted of 150 amino acid residues and their N-terminal Cys residues were blocked by an acetyl group. The amino acid sequences of LC17a and LC17b were common from the N-terminal to Glu-141 and five amino acid substitutions were observed within the remaining C-terminal 9 residues. The amino acid sequences of LC17a and LC17b were identical to those deduced from the nucleotide sequences of bovine aortic cDNAs encoding the two isoforms [Lash, J. A., Helper, D.J., Klug, M., Nicolozakes, A.W., & Hathaway, D.R. (1990) Nucleic Acids Res. 18, 7176]. PMID- 1500422 TI - Mitosis-specific phosphorylation of the nuclear oncoproteins Myc and Myb. AB - The c-myc and c-myb proto-oncogenes encode phosphorylated nuclear DNA binding proteins that are likely to be involved in transcriptional regulation. Here we demonstrate that both Myc and Myb proteins are hyperphosphorylated during mitosis. In the case of Myb, hyperphosphorylation is accompanied by the appearance of three M phase-specific tryptic phosphopeptides. At least one of these phosphopeptides corresponds to a phosphopeptide generated after phosphorylation of Myb in vitro by p34cdc2 kinase. By contrast, the mitotic hyperphosphorylation of Myc does not correlate with the appearance of unique phosphopeptides, suggesting that M phase and interphase sites may be clustered within the same peptides. In addition Myc does not appear to be a target for p34cdc2 phosphorylation. The hyperphosphorylated forms of Myc and Myb from mitotic cells are functionally distinct from the corresponding interphase proteins in that the former have reduced ability to bind nonspecificially to double-stranded DNA cellulose. Furthermore, mitotic Myb binds poorly to oligodeoxynucleotides containing an Myb response element. We surmise that the decreased DNA binding capacity of hyperphosphorylated Myb and Myc during M phase may function to release these proteins from chromatin during chromosome condensation. PMID- 1500423 TI - cdc25 is a nuclear protein expressed constitutively throughout the cell cycle in nontransformed mammalian cells. AB - A family of proteins homologous to the cdc25 gene product of the fission yeast bear specific protein tyrosine phosphatase activity involved in the activation of the p34cdc2-cyclin B kinase. Using affinity-purified antibodies raised against a synthetic peptide corresponding to the catalytic site of the cdc25 phosphatase, we show that cdc25 protein is constitutively expressed throughout the cell cycle of nontransformed mammalian fibroblasts and does not undergo major changes in protein level. By indirect immunofluorescence, cdc25 protein is found essentially localized in the nucleus throughout interphase and during early prophase. Just before the complete nuclear envelope breakdown at the prophase-prometaphase boundary, cdc25 proteins are redistributed throughout the cytoplasm. During metaphase and anaphase, cdc25 staining remains distributed throughout the cell and excludes the condensed chromosomes. The nuclear locale reappears during telophase. In light of the recent data describing the cytoplasmic localization of cyclin B protein (Pines, J., and T. Hunter. 1991. J. Cell Biol. 115:1-17), the data presented here suggest that separation in two distinct cellular compartments of the cdc25 phosphatase and its substrate p34cdc2-cyclin B may be of importance in the regulation of the cdc2 kinase activity. PMID- 1500424 TI - The rubella virus E1 glycoprotein is arrested in a novel post-ER, pre-Golgi compartment. AB - Evidence is accumulating that a distinct compartment(s) exists in the secretory pathway interposed between the rough ER (RER) and the Golgi stack. In this study we have defined a novel post-RER, pre-Golgi compartment where unassembled subunits of rubella virus (RV) E1 glycoprotein accumulate. When RV E1 is expressed in CHO cells in the absence of E2 glycoprotein, transport of E1 to the Golgi complex is arrested. The compartment in which E1 accumulates consists of a tubular network of smooth membranes which is in continuity with the RER but has distinctive properties from either the RER, Golgi, or previously characterized intermediate compartments. It lacks RER and Golgi membrane proteins and is not disrupted by agents which disrupt either the RER (thapsigargin, ionomycin) or Golgi (nocodazole and brefeldin A). However, luminal ER proteins bearing the KDEL signal have access to this compartment. Kinetically the site of E1 arrest lies distal to or at the site where palmitylation occurs and proximal to the low temperature 15 degrees C block. Taken together the findings suggest that the site of E1 arrest corresponds to, or is located close to the exit site from the ER. This compartment could be identified morphologically because it is highly amplified in cells overexpressing unassembled E1 subunits, but it may have its counterpart among the transitional elements of non-transfected cells. We conclude that the site of E1 arrest may represent a new compartment or a differentiated proximal moiety of the intermediate compartment. PMID- 1500425 TI - In AtT20 and HeLa cells brefeldin A induces the fusion of tubular endosomes and changes their distribution and some of their endocytic properties. AB - We have studied the effects of brefeldin A (BFA) on the tubular endosomes in AtT20 and HeLa cells (Tooze, J., and M. Hollinshead. 1991. J. Cell Biol. 115:635 653) by electron microscopy of cells labeled with three endocytic tracers, HRP, BSA-gold, and transferrin conjugated to HRP, and by immunofluorescence microscopy. For the latter we used antibodies specific for transferrin receptor, and, in the case of AtT20 cells, also antibodies specific for synaptophysin. In HeLa cells BFA at concentrations ranging from 1 micrograms to 10 micrograms/ml causes the dispersed patches of network of preexisting tubular early endosomes to be incorporated within 5 min into tubules approximately 50 nm in diameter but up to 40-50 microns long. These long, straight tubular endosomes are aligned along microtubules; they branch relatively infrequently to form an open network or reticulum extending from the cell periphery to the microtubule organizing center (MTOC). As the incubation with BFA is prolonged beyond 5 min, a steady state is reached in which many tubules are located in a dense network enclosing the centrioles, with branches extending in a more open network to the periphery. This effect of BFA, which is fully reversed within 15-30 min of washing out, is inhibited by pre-incubating the cells with sodium azide and 2-deoxy-D-glucose. In AtT20 cells BFA at 5 micrograms/ml or above causes the same sorts of changes, preexisting tubular endosomes are recruited into a more continuous endosomal network, and there is a massive accumulation of this network around the MTOC. Maintenance of the BFA-induced endosomal reticulum in both cell types is dependent upon the integrity of microtubules. In AtT20 cells BFA at 1 microgram/ml has no detectable effect on the early endosomal system but the Golgi stacks are converted to clusters of tubules and vesicles that remain in the region of the MTOC during prolonged incubations. Therefore, the Golgi apparatus in these cells is more sensitive to BFA than the early endosomes. The morphological evidence suggests that all the tubular early endosomes in BFA treated HeLa and AtT20 cells are linked together in a single reticulum. Consistent with this, incubations as short as 1-3 min with 10 or 20 mg/ml HRP in the medium result in the entire endosomal reticulum in most of the BFA-treated cells being filled with HRP reaction product.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1500426 TI - The insulin receptor juxtamembrane region contains two independent tyrosine/beta turn internalization signals. AB - We have investigated the role of tyrosine residues in the insulin receptor cytoplasmic juxtamembrane region (Tyr953 and Tyr960) during endocytosis. Analysis of the secondary structure of the juxtamembrane region by the Chou-Fasman algorithms predicts that both the sequences GPLY953 and NPEY960 form tyrosine containing beta-turns. Similarly, analysis of model peptides by 1-D and 2-D NMR show that these sequences form beta-turns in solution, whereas replacement of the tyrosine residues with alanine destabilizes the beta-turn. CHO cell lines were prepared expressing mutant receptors in which each tyrosine was mutated to phenylalanine or alanine, and an additional mutant contained alanine at both positions. These mutations had no effect on insulin binding or receptor autophosphorylation. Replacements with phenylalanine had no effect on the rate of [125I]insulin endocytosis, whereas single substitutions with alanine reduced [125I]insulin endocytosis by 40-50%. Replacement of both tyrosines with alanine reduced internalization by 70%. These data suggest that the insulin receptor contains two tyrosine/beta-turns which contribute independently and additively to insulin-stimulated endocytosis. PMID- 1500427 TI - In vitro and in vivo characterization of four fibroblast tropomyosins produced in bacteria: TM-2, TM-3, TM-5a, and TM-5b are co-localized in interphase fibroblasts. AB - Most cell types express several tropomyosin isoforms, the individual functions of which are poorly understood. In rat fibroblasts there are at least six isoforms; TM-1, TM-2, TM-3, TM-4, TM-5a, and TM-5b. TM-1 is the product of the beta gene. TM-4 is produced from the TM-4 gene, and TMs 2, 3, 5a, and 5b are the products of the alpha gene. To begin to study the localization and function of the isoforms in fibroblasts, cDNAs for TM isoforms 2, 3, 5a, and 5b were placed into bacterial expression vectors and used to produce TM isoforms. The bacterially produced TMs were determined to be full length by sequencing the amino- and carboxy termini. These TMs were found to bind to F-actin in vitro, with properties similar to that of skeletal muscle TM. In addition, competition experiments demonstrated that TM 5b was better than TM-5a in displacing other TM isoforms from F-actin in vitro. To investigate the intracellular localization of these fibroblast isoforms, each was derivatized with a fluorescent chromophore and microinjected into rat fibroblasts. TM-2, TM-3, TM-5a, and TM-5b were each found to associate along actin filaments. There was no preferred cellular location or subset of actin filaments for these isoforms. Furthermore, co-injection of two isoforms labeled with different fluorochromes showed identical staining. At the level of the light microscope, these isoforms from the alpha gene do not appear to achieve different functions by binding to particular subsets of actin filaments or locations in cells. Some alternative possibilities are discussed. The results show that bacterially produced TMs can be used to study in vitro and in vivo properties of the isoforms. PMID- 1500428 TI - 2-Deoxyglucose and cytochalasin D modulate aldolase mobility in living 3T3 cells. AB - Approximately 23% of the glycolytic enzyme aldolase in the perinuclear region of Swiss 3T3 cells is immobile as measured by FRAP. Previous studies suggest that the immobile fraction may be associated with the actin cytoskeleton (Pagliaro, L. and D. L. Taylor. 1988. J. Cell Biol. 107:981-991), and it has been proposed that the association of some glycolytic enzymes with the cytoskeleton could have functional significance, perhaps involving a fundamental relationship between glycolysis, cytoplasmic organization, and cell motility. We have tested the effect of a key glycolytic inhibitor and an actin cytoskeletal modulator on the mobility of aldolase in living cells directly, using fluorescent analog cytochemistry and FRAP. We report here that the competitive hexokinase inhibitor 2-deoxyglucose releases the bound fraction of aldolase in 3T3 cells within 10 min, and that this process is reversible upon washout of the inhibitor. A similar result is produced with the actin-binding agent, cytochalasin D. These results are consistent with models in which glycolytic enzymes are not exclusively diffusion-limited, soluble proteins, but may exist partially in the solid phase of cytoplasm. Such organization has significant implications for both the modulation of cytoplasmic structure and for cellular metabolism. PMID- 1500429 TI - Tubulin protofilaments and kinesin-dependent motility. AB - Microtubules are built of tubulin subunits assembled into hollow cylinders which consist of parallel protofilaments. Thus, motor molecules interacting with a microtubule could do so either with one or several tubulin subunits. This makes it difficult to determine the structural requirements for the interaction. One way to approach the problem is to alter the surface lattice. This can be done in several ways. Proto-filaments can be exposed on their inside (C-tubules or "sheets"), they can be made antiparallel (zinc sheets), or they can be rolled up (duplex tubules). We have exploited this polymorphism to study how the motor protein kinesin attached to a glass surface interacts and moves the various tubulin assemblies. Microtubules glide over the surface along straight paths and with uniform velocities. In the case of C-tubules, approximately 40% glide similarly to microtubules, but a major fraction do not glide at all. This indicates (a) that a full cylindrical closure is not necessary for movement, and (b) that the inside surface of microtubules does not support gliding. With zinc sheets, up to 70% of the polymers move, but the movement is discontinuous, has a reduced speed, and follows along a curved path. Since zinc sheets have protofilaments alternating in orientation and polarity, this result suggests that in principle a single protofilament can produce movement, even when its neighbors cannot. Duplex microtubules do not move because they are covered with protofilaments coiled inside out, thus preventing the interaction with kinesin. The data can be explained by assuming that the outside of one protofilament represents the minimal track for kinesin, but smooth gliding requires several parallel protofilaments. Finally, we followed the motion of kinesin-coated microbeads on sea-urchin sperm flagella, from the flagellar outer doublet microtubules to the singlet microtubule tips extending from the A-tubules. No change in behavior was detected during the transition. This indicates that even if these microtubules differ in surface lattice, this does not affect the motility. PMID- 1500430 TI - Distinct cellular expression pattern of annexins in Hydra vulgaris. AB - The annexins are a structurally related family of Ca2+ and phospholipid binding proteins whose function has not been clearly defined. Further investigations of annexin function may be enhanced by studying simpler organisms that express fewer annexin gene products. We previously characterized annexin XII from the freshwater cnidarian Hydra vulgaris (Schlaepfer, D. D., D. A. Fisher, M. E. Brandt, H. R. Bode, J. Jones, and H. T. Haigler. 1992. J. Biol. Chem. 267:9529 9539). In this report, we detected one other hydra annexin (40 kD) by screening hydra cell extracts with antibodies raised against peptides from highly conserved regions of known annexins. The 40-kD protein was expressed at less than 1% of annexin XII levels. These biochemical studies indicate that hydra contain a very limited number of annexin gene products. The cellular hydra annexin distribution was analyzed by indirect immunofluorescence. Using affinity-purified antibodies to annexin XII, the epithelial battery cells were stained throughout the tentacle. A lower level of annexin XII staining was detected in peduncle region epithelial cells. No other cell types showed detectable annexin XII staining. The anti-peptide antibody that specifically detected the 40-kD hydra annexin, maximally stained the cytoplasm of nematocytes. The immunofluorescent results showed that annexin XII and the 40-kD annexin were not co-expressed in the same cells. Since the hydra annexins localized to specific subsets of the total hydra cell types, it is likely that these proteins perform specialized biological roles, and not general "housekeeping" functions which are part of the essential molecular machinery of all cells. PMID- 1500431 TI - Enteric defensins: antibiotic peptide components of intestinal host defense. AB - Five intestinal defensins, termed cryptdins 1-5, have been purified from mouse small bowel, sequenced, and localized to the epithelium by immunohistochemistry. Although identified as members of the defensin peptide family by peptide sequencing, enteric defensins are novel in that four cryptdins have amino termini which are three to six residues longer than those of leukocyte-derived defensins. A fifth cryptdin is the first defensin to diverge from the previously invariant spacing of cysteines in the peptide structure. The most abundant enteric defensin, cryptdin-1, had antimicrobial activity against an attenuated phoP mutant of Salmonella typhimurium but was not active against the virulent wild type parent. Immunohistochemical localization demonstrated that cryptdin-1, and probably cryptdins 2 and 3, occur exclusively in Paneth cells, where the peptides appear to be associated with cytoplasmic granules. Biochemical and immunologic analysis of the luminal contents of the small intestine suggest that cryptdin peptides are secreted into the lumen, similar to Paneth cell secretion of lysozyme. The presence of several enteric defensins in the intestinal epithelium, evidence of their presence in the lumen, and the antibacterial activity of cryptdin-1 suggest that these peptides contribute to the antimicrobial barrier function of the small bowel mucosa. PMID- 1500432 TI - Proteolytic processing of endogenous and recombinant beta 4 integrin subunit. AB - The alpha 6 beta 4 integrin is a receptor involved in the interaction of epithelial cells with basement membranes. This integrin is unique among the known integrins in that its beta 4 subunit has a large cytoplasmic domain. The function of this cytoplasmic domain is not known. In this paper we show that the beta 4 subunit undergoes proteolytic processing in cultured cells and provide evidence that this also happens in tissues. Immunoprecipitation experiments indicated that the cytoplasmic domain of beta 4 is susceptible to a calcium-dependent protease present in cellular extracts. In vitro assays with purified calpain showed that this enzyme can cleave beta 4 at two distinct sites in the cytoplasmic domain, generating truncated molecules of 165 and 130 kD. Immunoblotting experiments performed on cultured epithelial cells using an antibody to a peptide modeled after the COOH-terminus of the beta 4 subunit showed 70-kD fragments and several fragments of molecular masses between 185 and 115 kD. Similar fragments were detected in CHO cells transfected with the full-length beta 4 cDNA, but not in control transfected cells or in cells transfected with a mutant cDNA lacking the epitope of the cytoplasmic peptide antibody. The sizes of the fragments indicated that both the intracellular and extracellular domains of beta 4 are proteolytically processed. To examine the processing of the beta 4 subunit in epithelial tissues in vivo, human skin frozen sections were stained with antibodies to the ectodomain or the cytoplasmic domain of beta 4. The distinct staining patterns obtained with the two types of antibodies provided evidence that beta 4 is proteolytically processed in vivo in skin. Analogous experiments performed on sections of the cornea suggested that beta 4 is not proteolytically processed at a detectable level in this tissue. Thus, cleavage of the beta 4 subunit occurs in a tissue-specific fashion. These results suggest a potential mechanism of modulating the activities of the alpha 6 beta 4 integrin. PMID- 1500434 TI - Structure and dynamics of transcriptionally active chromatin. PMID- 1500435 TI - Behaviour of ejaculated spermatozoa from bull, boar and ram during thin-layer countercurrent partition in aqueous two-phase systems. AB - Ejaculated spermatozoa from bulls, boars and rams were subjected to thin-layer countercurrent partition in aqueous two-phase systems composed of dextran T500 and polyethylene glycol 6000 (PEG) in sucrose-based Hepes-buffered media. In the basal system, the great majority of spermatozoa tended to partition with the dextran-rich bottom phase; however, by including very low levels of phosphate, they could be made to partition increasingly with the PEG-rich top phase (complete at 10 mM phosphate). A procedure was developed for carrying out four separations simultaneously under identical conditions, whereby it could be shown that distribution varied with the number of spermatozoa in the sample. In the case of bull, the effect of cell number could be reduced considerably by inclusion of small quantities of seminal plasma in the phase system, but no such effect was found for ram or boar. Considerable variation in distribution pattern was seen between samples, which did not appear to be due to technical inconsistency. Livability in the phase systems was also variable, and we believe that PEG may exert a detergent-like effect on the sperm surface that is exacerbated in highly defined media free of protective proteins. PMID- 1500433 TI - Molecular cloning of amphiglycan, a novel integral membrane heparan sulfate proteoglycan expressed by epithelial and fibroblastic cells. AB - We have synthesized an antisense oligonucleotide primer that matches a supposedly conserved sequence in messages for heparan sulfate proteoglycans with transmembrane orientations. With the aid of this primer we have amplified partial and selected full-length copies of a message from human lung fibroblasts that codes for a novel integral membrane heparan sulfate proteoglycan. The encoded protein is 198 amino-acids long, with discrete cytoplasmic, transmembrane, and amino-terminal extracellular domains. Except for the sequences that represent putative heparan sulfate chain attachment sites, the extracellular domain of this protein has a unique structure. The transmembrane and cytoplasmic domains, in contrast, are highly similar to the corresponding domains of fibroglycan and syndecan, the two cell surface proteoglycans that figured as models for the design of the antisense primer. This similarity includes the conservation of four tyrosine residues, one immediately in front of the stop transfer sequence and three in the cytoplasmic segment, and of the most proximal and most distal cytoplasmic sequences. The cDNA detects a single 2.6-kb message in cultured human lung fibroblasts and in a variety of human epithelial and fibroblastic cell lines. Polyclonal and monoclonal antibodies raised against the encoded peptide after expression as a beta-galactosidase fusion protein react with the 35-kD coreprotein of a cell surface heparan sulfate proteoglycan of human lung fibroblasts and decorate the surface of many cell types. We propose to name this proteoglycan "amphiglycan" (from the Greek words amphi, "around, on both sides of" and amphoo, "both") referring to its domain structure which extends on both sides of the plasmamembrane, and to its localization around cells of both epithelial and fibroblastic origin. PMID- 1500436 TI - Morphometric studies of pancreatic acinar granule formation in NCTR-Balb/c mice. AB - NCTR-Balb/c mice are afflicted with a cholesterol lysosomal storage disorder stemming from a defect in intracellular cholesterol processing. The clinical and biochemical abnormalities expressed in the mice resemble Niemann-Pick type C and D disorders in humans. One of the proposed mechanisms to explain the pathophysiology of the disorder implies a defect in the process of membrane transport that normally takes place in the vesicular movement of cholesterol to specific target sites in the cell. Secretory granule formation in pancreatic acinar cells is one of the biological processes known to involve massive membrane flow. Thus, we have undertaken a morphometric study of the regranulation mechanism in the pancreatic acinar cells of the mutant mice, as a way of studying cellular membrane movement. Electron micrographs of pancreatic acinar cells from mutant and normal mice were taken at several time points after extensive degranulation induced by pilocarpine injection. Two hours after stimulation the pancreatic cells demonstrated a complete loss of granules, and at later time points newly formed granules appeared. Identical unit granule volumes were observed in both groups, indicating that the progranules were of normal size. However, the rate of granule formation and maturation was reduced in the mutant mice, which might be the result of a defect in membrane function. PMID- 1500437 TI - Dynamics of transmembrane proteins during Sindbis virus budding. AB - Label-fracture and immunogold fracture-flip techniques are used to address at the ultrastructural level the dynamics of viral and cellular transmembrane proteins during the budding of Sindbis virus on the plasma membrane of infected cells. Immunolabeling with anti-Sindbis spike antibodies shows that the viral proteins are mostly in clusters, all associated with budding viruses. Ultrastructural observation of the unlabeled freeze-fractured plasma membranes shows that membrane particles aggregate over the budding viruses. These results indicate that the concentration of viral transmembrane proteins gives rise to a parallel concentration of membrane particles. Immunolabeling with anti-CD8 antibodies of cells expressing by transfection the CD8 transmembrane protein and infected with Sindbis virus shows absence of labeling on the particle aggregates over the forming virions. These findings indicate the exclusion of CD8 proteins from the portions of the membrane where budding occurs. PMID- 1500438 TI - Identification of a large pre-lysosomal compartment in the pathogenic protozoon Trypanosoma cruzi. AB - Epimastigote forms of the pathogenic parasite Trypanosoma cruzi were used to study the endocytic process in a protozoon. These elongated unicellular organisms are highly polarized cells: endocytosis occurs only at the anterior region through the cytostome and the flagellar pocket membrane, areas of the plasma membrane where the cell cytoskeleton, formed by sub-pellicular microtubules, is absent. When the cells were incubated at 4 degrees C or 28 degrees C with gold labeled transferrin, fixed and processed for routine transmission electron microscopy our observations show that this ligand initially binds to the cytosome and the membrane lining the flagellar pocket and is subsequently ingested through a clathrin-independent receptor-mediated endocytotic process, with formation of uncoated pits and vesicles. Ingested complexes are carried in uncoated vesicles to the reservosomes, large membrane-bound organelles found mostly at the posterior end of the cell. Immunocytochemical data from Lowicryl-embedded cells demonstrated that the reservosomes are acidic compartments (pH 6.0, as shown using DAMP as a pH probe) with no acid phosphatase or typical lysosome-associated membrane proteins (LAMP 1, LAMP 2 and lgp 120), but rich in cysteine proteinase. These data suggest that the reservosome is a pre-lysosomal compartment. Since cysteine proteinase of T. cruzi contains no phosphorylated mannose residues and the cation-independent mannose 6-phosphate receptor could not be immunocytochemically detected in the reservosomes, it is possible that lysosomal enzymes in the epimastigote forms of T. cruzi are targeted to compartments related to the endocytic pathway through a mechanism different from that which occurs in other eukaryotic cells. PMID- 1500439 TI - Identification of the intermediate filament-associated protein gyronemin as filamin. Implications for a novel mechanism of cytoskeletal interaction. AB - In a previous paper, a monoclonal antibody (designated M1.4) that recognized a 240 kDa polypeptide was characterized. This antibody stained the intermediate filaments in several cell lines, and biochemical characteristics of the 240 kDa polypeptide led us to conclude that it was a novel intermediate filament associated protein, which we termed gyronemin. Here we report that gyronemin is expressed in adult rat organs that contain a substantial smooth muscle component. Taking advantage of this observation, this protein was purified from bovine uterine tissue and, by biochemical, immunological and amino acid sequence analysis, found to be homologous to the actin-associated protein filamin. Three novel monoclonal antibodies raised using purified bovine gyronemin as the immunogen show this protein to be associated with actin-containing stress fibers, although our original M1.4 antibody continued to be localized along vimentin filaments. Since two-dimensional electrophoretic analysis did not demonstrate a difference in either relative molecular mass or isoelectric point of this polypeptide when associated with either filamentous system, we conclude that filamin is a bifunctional protein capable of associating with both the intermediate filament and actin cytoskeletal systems. PMID- 1500440 TI - Involvement of the consensus sequence motif at coil 2b in the assembly and stability of vimentin filaments. AB - Nearly all intermediate filament (IF) proteins share two sequence motifs located at the N- and the C-terminal ends of their helical rod domain ('coil 1a' and 'coil 2b', respectively). To examine the structural role of the coil 2b motif, we have performed in vitro assembly studies and in vivo microinjection experiments employing two site-specific reagents: (a) a 20-residue synthetic peptide (C-2) representing the conserved motif itself and (b) a monoclonal antibody (anti-IFA) that recognises an epitope within the conserved coil 2b sequence. We demonstrate here that vimentin protofilaments, when induced to assemble in the presence of C 2 or anti-IFA, show a lower propensity to polymerise and yield various abberant structures. The few filaments that are formed under these conditions appear much shorter than normal IFs and are unravelled or aggregated. Furthermore, when preformed vimentin filaments are exposed to C-2 or anti-IFA, most of the normal IFs are converted into shorter filamentous forms that possess an abberant morphology. None of these effects is seen when vimentin subunits are coincubated with control peptides. Microinjection of anti-IFA into the cytoplasm of interphasic 3T3 cells provokes collapse of vimentin IFs into a juxtanuclear mass and formation of numerous amorphous aggregates distributed throughout the cytoplasm. These two effects are not seen when the anti-IFA is microinjected into the cell nucleus. Our results provide experimental evidence supporting previous suggestions for a role for the conserved coil 2b sequence in filament assembly. We propose that this region is interacting with other sites along the vimentin molecule and that these interactions are essential for proper protofilament protofilament alignment and filament stability. PMID- 1500441 TI - Vertebrate p34cdc2 phosphorylation site mutants: effects upon cell cycle progression in the fission yeast Schizosaccharomyces pombe. AB - We have used the fission yeast Schizosaccharomyces pombe to analyse the effects of in vitro mutagenesis of the four known phosphorylation sites in the chicken p34(cdc2) protein, Thr 14, Tyr 15, Thr 161 and Ser 277, upon cell cycle progression. We have studied both the effect of overexpression of mutant proteins in a cdc2+ background and assayed their ability to rescue null and temperature sensitive alleles of cdc2. Mutations of Thr 14 and Tyr 15 within the ATP binding domain of p34(cdc2) that mimic constitutive phosphorylation cause dominant negative cell cycle arrest when overexpressed. In contrast, some substitutions that simulate permanent dephosphorylation of the corresponding sites advance dephosphorylation of the corresponding sites advance mitosis. These data confirm the model that p34(cdc2) function is negatively regulated by phosphorylation of residues in the ATP binding site. Mutagenesis of the conserved residue Thr 161 functionally inactivates p34(cdc2), and our data suggest that both phosphorylation and dephosphorylation events at Thr 161 are required for progression through the cell cycle. Mutations at the fourth site of phosphorylation. Ser 277, lead to cold-sensitive cell cycle arrest, in minimal but not rich growth medium, suggesting that this site is involved in monitoring the nutritional status of the cell. PMID- 1500442 TI - Extrajunctional distribution of N-cadherin in cultured human endothelial cells. AB - Human endothelial cells contain prominent Ca(2+)-dependent intercellular adherens type junctions (AJ), which are associated, at their cytoplasmic surfaces, with actin, vinculin and plakoglobin. The transmembrane adhesion molecules present in these sites are members of the cadherin family, which are recognized by a pancadherin serum, directed against the conserved C terminus of these molecules. Immunoblotting analysis of cultured human endothelial cells using these antibodies revealed three immunoreactive bands with apparent molecular masses of 135, 130 and 120 kDa. Cloning and sequencing of the 135 kDa cadherin from an endothelial cDNA expression library indicated that this molecule is a typical cadherin, essentially identical to N-cadherin. Transfection of cDNA encoding this molecule into CHO cells resulted in the induction of AJ formation and an apparent epithelialization of the cells. Immunofluorescent labeling with antibodies to chicken N-cadherin indicated that the molecule is associated with intercellular junctions in the transfectants. In contrast, cultured human umbilical cord endothelial cells exhibited a largely diffuse N-cadherin labeling over the entire cell surface with only occasional enrichment in cell-cell junctions. Comparison of this pattern with the discrete junctional labeling obtained with the pan cadherin antibody suggests that different cadherins, co-expressed in the same endothelial cells, may undergo differential surface distribution. PMID- 1500443 TI - Preparative chromatographic separation of enantiomers. AB - The potential of the chromatographic separation of enantiomers on a preparative scale as a tool for the isolation of optically pure compounds is gaining increasing recognition. This review surveys the different chiral stationary phases (CSPs) used for preparative chromatography, emphasizing the advantages and drawbacks of each. The strategy to be followed for preparative separations is discussed and tables summarizing separations reported in the literature give an overview of practical applications. Cellulose triacetate has been used most frequently, probably because of its broad application range and its low production costs in comparison with more recently introduced CSPs. Nevertheless, the high efficiency of some of the novel CSPs is likely to contribute to the further development and expansion of the method. PMID- 1500444 TI - Separation and identification of the 4-hydroxyantipyrine sulphoconjugate. AB - In a previous study we observed, during separation of total antipyrine metabolites by high-performance liquid chromatography and after enzymatic hydrolysis, an unidentified peak corresponding to an ionic compound with pyrazolinone features. In the present study, this compound was identified as the 4-hydroxyantipyrine sulphoconjugate, and its structure was definitively confirmed by gas chromatographic-mass spectrometric analysis and by the use of pure synthetic substance. We also demonstrated the inhibitory effect of sodium metabisulphite, a necessary preservative of urinary samples, on hydrolysis of this conjugate in the presence of sulphatases from Helix pomatia or Aerobacter aerogenes. This inhibitory effect makes it impossible to perform a global assay of antipyrine metabolites after enzymatic or chemical hydrolysis and confirms the value of direct assay of the 4-hydroxyantipyrine sulphoconjugate. PMID- 1500446 TI - Determination of piroxicam and its major metabolites in the plasma, urine and bile of humans by high-performance liquid chromatography. AB - A simple and sensitive liquid chromatographic method with ultraviolet detection is described for the determination of the nonsteroidal anti-inflammatory drug piroxicam and its major metabolites in human plasma, urine and bile. Separation of these components occurs on a reversed phase C10CN column with a mobile phase consisting of acetonitrile-water-sodium dihydrogenphosphate solution. The detection limit of the assay was 50 ng/ml with intra- and inter-assay coefficients of variation for piroxicam of the order of 2 and 5%, respectively. The assay linearity was good (typically r = 0.9999). This method can be readily utilised for clinical pharmacokinetic and mass-balance studies. PMID- 1500445 TI - Quantitative analysis of retinoids in biological fluids by high-performance liquid chromatography using column switching. III. Determination of the arotinoid sumarotene and its Z-isomer in human and animal plasma. AB - A fully automated and sensitive high-performance liquid chromatographic method, using on-line solid-phase extraction, automated column switching and ultraviolet detection, was developed for the third-generation retinoid (arotinoid) sumarotene (methyl p-[(E)-2-(5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthyl)propenyl]phe nyl sulphone; Ro 14-9706) and its Z-isomer. Nearly quantitative recoveries for human, rat and dog plasma were obtained by addition of acetonitrile (final content ca. 17%) to the plasma sample prior to injection. No isomerization was observed when the samples were stored in the autosampler for more than 20 h. The injection volume was 0.5 ml, resulting in quantification limits of 1 ng/ml for sumarotene and 2 ng/ml for the Z-isomer. More than 40 injections could be made on to one precolumn, allowing routine overnight injections. Using a 1-ml injection volume, the limit of quantification for sumarotene could be improved to 0.5 ng/ml. The method was applied to toxicokinetic studies in rats and dogs, and was used to monitor human plasma samples after repeated topical application. The method could also be adapted to etarotene (Ro 15-1570), which was used as an internal standard, and which is at present in clinical development. PMID- 1500447 TI - Reversed-phase ion-pair high-performance liquid chromatographic determination of triclabendazole metabolites in serum and urine. AB - An ion-pair high-performance liquid chromatographic method was developed for measuring the concentrations of triclabendazole metabolites (sulphoxide and sulphone) in plasma and urine samples. The diluted biological fluids are ultrafiltered before chromatography through a 30,000 relative molecular mass cut off filter and then injected into a C18 column. They are then isocratically eluted with a mobile phase consisting of 0.05 M phosphate buffer (pH 7.0) acetonitrile (55:45, v/v) with addition of 1.0 mmol/l sodium decanesulphonate and monitored by ultraviolet-visible spectrophotometry at 312 nm. Recoveries over the range 0.01-9.0 micrograms/ml for triclabendazole sulphoxide and sulphone are, respectively, 91.7% and 91.6% in serum and 90.3% and 90.2% in urine. For both metabolites, the limit of detection is 10 ng/ml in both urine and serum. PMID- 1500448 TI - Determination of the coumarin derivative cloricromene acid in rabbit plasma and platelets. AB - Two methods for the determination of cloricromene acid in biological samples are described. Cloricromene acid is a catabolite of cloricromene, a coumarin derivative which is active in the cardiovascular system. After oral administration of cloricromene to a rabbit, plasma and platelets were taken at different times and cloricromene acid was then isolated by solid-phase extraction with Sep-Pak C18 cartridges using acetonitrile-tetrahydrofuran-20% aqueous acetic acid (15:11:74, v/v/v) as eluent. The analyses were performed by reversed-phase high-performance liquid chromatography (RP-HPLC) combined with fluorescence detection with excitation at 310 nm and emission at 390 nm. The limit of quantification by RP-HPLC was about 50 pg. The catabolite in the plasma was identified by continuous-flow fast atom bombardment mass spectrometry (CF-FAB MS), also used as a complementary means of RP-HPLC determination. The results obtained by RP-HPLC and CF-FAB-MS showed good agreement. PMID- 1500450 TI - Simple, rapid and sensitive determination of plasma taurine by high-performance liquid chromatography using pre-column derivative formation with fluorescamine. AB - A simple, rapid and sensitive method for the determination of plasma taurine by high-performance liquid chromatography in the isocratic mode has been developed. The deproteinized plasma was treated with fluorescamine. These derivatives were separated on a LiChrospher 100 RP-8 column within 15 min. The detection limit for taurine was 0.2 microM. The plasma taurine contents of yellowtail fish, Seriola quinqueradiata, beef cattle, dairy cows and chickens were determined to be 125 +/ 54, 5.6 +/- 1.4, 2.2 +/- 0.7 and 20.0 +/- 9.6 micrograms/ml, respectively. PMID- 1500449 TI - Rapid separation of creatine, phosphocreatine and adenosine metabolites by ion pair reversed-phase high-performance liquid chromatography in plasma and cardiac tissue. AB - A rapid ion-pair reversed-phase high-performance liquid chromatographic method has been developed for the simultaneous detection of creatine, phosphocreatine, hypoxanthine, inosine, adenosine, AMP, ADP, ATP, 8-azaguanine, 2-chloroadenosine, and 2'-O-methyladenosine. This method has proven useful for measuring changes in nucleotide concentrations in both heart tissue and plasma samples. Separation of the compounds of interest is achieved in less than 8 min with re-equilibration in 7 min, making the total run time 15 min. Separation is performed on a 3-microns Ultrasphere ODS column employing tetrabutylammonium phosphate as the ion-pair agent and dipotassium hydrogenphosphate as the counter ion. The accuracy, rapid separation, and re-equilibration time make this method particularly useful for the routine analysis of a large number of samples. PMID- 1500451 TI - Bioanalysis of the investigational anti-tumour drug 5,10-dideaza-5,6,7,8 tetrahydrofolic acid by high-performance liquid chromatography with ultraviolet detection. AB - A high-performance liquid chromatographic (HPLC) method with ultraviolet detection at 278 nm is presented for the determination of 5,10-dideaza-5,6,7,8 tetrahydrofolic acid in plasma. Sample pretreatment was achieved by using cation exchange solid-phase extraction columns with methotrexate as internal standard. Chromatographic separation was based on ion-pair HPLC with 1-octanesulphonic acid as the ion-pairing compound. The detection limit was 10 ng/ml using an 500 microliters sample volume. The assay was linear from the detection limit up to 5000 ng/ml with good reproducibility. The applicability of the assay was demonstrated in a study in the rat. PMID- 1500452 TI - Determination of valproic acid by high-performance liquid chromatography with photodiode-array and fluorescence detection. AB - The derivatization of valproic acid and undecylenic acid with 4-bromomethyl-7 methoxycoumarin is described. The derivatives were detected by photodiode-array and fluorescence detectors. The optimum monitoring conditions and the stability of the suspension solution and derivatives were investigated. A high-performance liquid chromatographic (HPLC) method with isocratic or gradient elution has been established for the analysis. This method has been used for the determination of total and free valproic acid in serum. There is a satisfactory correlation between the results obtained by this HPLC method and those measured by the enzyme immunoassay. Some other common anti-epileptic drugs did not interfere with the analysis. The method is simple and fast and has better sensitivity and linearity than enzyme immunoassay. It is suited for routine therapeutic drug monitoring. PMID- 1500453 TI - Determination of glycyrrhizin in rabbit plasma by high-performance liquid chromatography with photodiode-array ultraviolet detection and its pharmacokinetics application. AB - A simple and sensitive high-performance liquid chromatographic method for the determination of glycyrrhizin in rabbit plasma has been developed. Up to 0.1 ml of plasma containing glycyrrhizin was deproteinized by acetonitrile, which contained an internal standard (indomethacin). The supernatant was injected onto a LiChrospher RP-18 column using a methanol-water-ammonia solution (80:20:0.1, v/v, pH 3.0-3.2, adjusted with perchloric acid) as the mobile phase and ultraviolet detection at 254 nm, followed by ultraviolet spectrum identification (between 200 and 380 nm) with a photodiode-array detector. The method is rapid, easily reproduced, selective and sensitive. It was applied to pharmacokinetic studies of glycyrrhizin in rabbit, after a 2 mg/kg intravenous administration. A biphasic phenomenon with a rapid distribution followed by a slower elimination phase was observed from the plasma concentration-time curve. Compartmental analysis yielded a two-compartment model. PMID- 1500454 TI - Simultaneous determination of a new gastrointestinal prokinetic agent (HSR-803) and its metabolites in human serum and urine by high-performance liquid chromatography using automated column-switching. AB - A method based on high-performance liquid chromatography using column-switching is described for the simultaneous determination of HSR-803 and its metabolites in human serum and urine. The system uses a six-port valve with a Nucleosil CN pre column for on-line sample clean-up, and direct injection of samples. The limits of quantitation in serum and urine were 5 and 20 ng/ml for HSR-803 and 50 and 200 ng/ml for the metabolites, respectively. The coefficients of variation for the intra- and inter-day accuracies were between 0.8 and 7.1% for each compound. This method was applied to the pharmacokinetic studies in humans after oral administration of HSR-803. PMID- 1500455 TI - Analytical studies on the chiral separation and simultaneous determination of pantothenic acid and hopantenic acid enantiomers in rat plasma by gas chromatography-mass fragmentography: a reply. PMID- 1500456 TI - Simultaneous determination of cortisol and cortisone in human plasma by stable isotope dilution mass spectrometry. AB - A method for the simultaneous determination of cortisol and cortisone in human plasma was developed using capillary gas chromatography-mass spectrometry selected ion monitoring. [2H5]Cortisol and [2H5]cortisone were used as internal standards. Cortisol and cortisone in plasma were determined from the peak-height ratios of the [M-31] fragment ions of the methoxime-trimethylsilyl derivatives of cortisol and [2H5]cortisol (m/z 605 and 610) and of cortisone and [2H5]cortisone (m/z 531 and 536). Sensitivity, specificity, precision, accuracy and reproducibility of the method were demonstrated to be satisfactory for measuring the circulating concentrations of cortisol and cortisone. PMID- 1500457 TI - Simple and rapid method for determination of short-chain fatty acids in biological materials by high-performance liquid chromatography with ultraviolet detection. AB - A new and versatile method for the identification and quantification of short chain fatty acids, such as formic, acetic, propionic, butyric, isobutyric, valeric, isovaleric and mercaptoacetic acids, in biological specimens by high performance liquid chromatography is described. After sample purification by vacuum transfer and concentration by alkaline freeze-drying, the acids were measured without any further preparative step, using a sulphonated polystyrene divinylbenzene column as stationary phase. Ultraviolet detection of the native acids was done at 214 nm. Peak resolution and reproducibility were as good as with gas chromatography. Many examples of the application of this method to a variety of biological specimens and fluids both from the rats and humans are described. PMID- 1500459 TI - Single-step method for purification of human transferrin from a by-product of chromatographic fractionation of plasma. AB - A rapid, simple and convenient method is described for the isolation, on a pilot scale, of pure and functional human transferrin from an unexploited by-product of chromatographic fractionation of plasma. In a single chromatographic step on DEAE Spherodex, 97% pure transferrin was obtained in 75% yield. A virus inactivation treatment was included in the preparative process in order to guarantee the safety of the final product, which could be used in culture media. PMID- 1500458 TI - Determination of free N-acetylamino acids in biological samples and N-terminal acetylamino acids of proteins. AB - N-Acetylamino acids were derivatized with 9-anthryldiazomethane to the corresponding esters. The anthryl esters were separated by high-performance liquid chromatography and detected fluorimetrically (excitation at 365 nm; fluorescence emission measured at 412 nm). N-Acetyl derivatives of Asn, Gln, Ser, Thr, Gly, Ala, Tyr, Pro, Met, Val, Ile and Leu as well as N-formyl-Met could be separated and identified in the same chromatographic run. The detection limit was from 0.10 pmol for AcGln to 5.5 pmol for AcIle and AcLeu. When the acetylamino acids listed above were added to the 700 g supernatant of a rat liver homogenate, the mean recovery was 72%. AcAla and AcTyr were found in free form in baker's yeast. Proteins with an acetylated N-terminus were digested by a protease, and the peptides formed were treated with an N-acylamino acid-releasing enzyme. This method was applied to end-group determination of four proteins (each 0.5 nmol). PMID- 1500460 TI - Determination of alkaline phosphatase isoenzymes in serum by high-performance liquid chromatography with post-column reaction detection. AB - A weak anion-exchange high-performance liquid chromatographic procedure with post column reaction detection for simultaneous determination of alkaline phosphatase (EC 3.1.3.1, ALP) isoenzymes is described. We identified six peaks with ALP isoenzyme activity in normal serum. The peaks were, in order of elution, one intestinal/bone, two bone and three liver ALP isoenzymes. This new assay with automatic injection, on-line post-column reaction detection and powerful integration data system could be of significant value in the routine clinical biochemistry laboratory. The advantages include improved sensitivity and selectivity over previous methods for the determination of ALP isoenzymes. PMID- 1500461 TI - Dye-affinity purification of transthyretin from an unexploited by-product of human plasma chromatographic fractionation. AB - Dye-affinity chromatography of human plasma transthyretin on Remazol Yellow GGL Sepharose from an unexploited by-product of chromatographic fractionation of plasma was optimized for large-scale preparation of a therapeutic product. With this system, transthyretin is only weakly bound to the gel. The residence time on gel and the transthyretin level in the by-product were observed to have no influence on the binding capacity of gel, and the optimum amount of transthyretin to be applied to the gel was found to be 1 g/l of gel. The adsorbent can be used more than ten times. The procedure resulted in the isolation, with a 30% yield with respect to plasma, of an 80% pure protein, which retained its thyroxine binding capacity. Although the purity is acceptable for substitutive therapy, it can be improved further with a second chromatography on Cibacron Blue-Sepharose. PMID- 1500462 TI - Quantification of erythrocyte S-adenosyl-L-methionine levels and its application in enzyme studies. AB - A highly selective high-performance liquid chromatographic method for the quantification of human erythrocyte S-adenosyl-L-methionine levels is described. A strong cation-exchange sorbent with propylsulphonic acid functional groups was used to extract S-adenosyl-L-methionine and S-adenosylethionine (internal standard) from erythrocytes. Quantification of erythrocyte S-adenosyl-L methionine levels was achieved by using reversed-phase high-performance liquid chromatography and ultraviolet detection at 254 nm. This method was adapted to measure methionine-adenosyltransferase activity in erythrocytes, which enables us to study the possible role of altered methylation in different diseases. PMID- 1500463 TI - Specific gas chromatography-mass spectrometry analytical method for the determination of cyhexatin in animal feed. AB - The acaricide tricyclohexyltin hydroxide (cyhexatin) was determined in animal feed samples, using gas chromatographic--mass spectrometry in the electron impact mode. Sample extraction and derivatization (converting the analyte to an alkylated derivative) were performed using a tricyclopentyl analogue of this acaricide as internal standard to obtain a better analytical precision. PMID- 1500464 TI - Simplified derivatization for determining sphingolipid fatty acyl composition by gas chromatography-mass spectrometry. AB - A simple procedure for simultaneously derivatizing non-hydroxy and hydroxy fatty acids prior to GC analysis [I. Ciucanu and F. Kerek, J. Chromatogr., 284 (1984) 179] has been evaluated for its usefulness in determining sphingolipid acyl composition. The method uses methyl iodide in polar aprotic solvents to generate methyl esters of carboxyl groups and methyl ethers of hydroxyl groups. Methylation efficiency is examined as a function of hydroxyl group presence and location in free fatty acids as well as a function of 2-hydroxy fatty acid chain length. Conditions are also reported for efficient saponification and derivatization of sphingolipid fatty acyl chains as is illustrated using bovine brain galactosylceramide. PMID- 1500465 TI - Determination of diclazuril in animal feed by liquid chromatography. AB - A method is described for the determination of diclazuril (Janssen Research Compound R64433; trademark Clinacox) in chicken feed at the mg kg(-1) level. Compound R062646, a structure analogous to diclazuril, was used as the interna standard. The drug was extracted from food with acidified methanol. Diclazuril was then isolated by means of solid-phase extraction with a cartridge containing a C18 phase. The eluate was evaporated and the residue redissolved in dimethylformamide. An aliquot was injected onto a reversed-phase high-performance liquid chromatographic column and the drug substance quantified at 280 nm by an ultraviolet detector. Extraction (absolute) recoveries of 85% for both internal standard and diclazuril were obtained. The method is suitable for diclazuril concentrations ranging from 0.1 to 1.5 mg kg(-1). Method validation data are presented. PMID- 1500466 TI - Determination of the unusual amino acid hypusine at the lower picomole level by derivatization with 4-dimethylaminoazobenzene-4'-sulphonyl chloride and reversed phase high-performance or medium-pressure liquid chromatography. AB - Hypusine, an unusual amino acid formed by post-translational modification of lysine, is normally determined by specific metabolic labelling followed by measurement of released radioactivity after protein hydrolysis. This paper describes a sensitive non-radioactive method for the determination of hypusine, involving complete protein hydrolysis and precolumn derivatization of the released amino acids with 4-dimethylaminoazobenzene-4'-sulphonyl chloride, followed by reversed-phase high-performance or medium-pressure liquid chromatography of the dabsylated derivatives. The detection limit of hypusine was about 500 fmol. Additionally, the hypusine-containing protein from the archaebacterium Sulfolobus acidocaldarius was purified. By applying the dabsylation method to the analysis of tryptic peptides derived from this protein, it was possible to determine the correct positioning of the hypusine residue in the amino acid sequence, which was not possible by the amino acid sequencing procedure alone. PMID- 1500467 TI - High pregnancy rates after oocyte and embryo donation. PMID- 1500468 TI - Resumption of pituitary and ovarian activity post-partum: endocrine and ultrasonic observations in bromocriptine-treated women. AB - The resumption of pituitary and ovarian activity was investigated by hormonal measurements and ultrasound scanning in 45 healthy post-partum women who were treated with bromocriptine. Bromocriptine, 50 mg (Parlodel LAR) was administered within 24 h post-partum. Plasma luteinizing hormone, follicle stimulating hormone, oestradiol, progesterone and prolactin concentrations were measured repeatedly and correlated with ultrasound measurements. Forty-one of the 45 women completed the study. A prompt fall in prolactin levels to normal (non-pregnant) values was observed within 24 h post-partum. Hereafter, a rapid return of the normal menstrual cycle was observed. Endocrine evidence of ovulation was obtained in 19/41 women within 1 month post-partum. Ultrasound measurements started at day 10 and were repeated regularly in 40 women. Ultrasound evidence of ovulation was found in 25/40 women. Ultrasound findings appeared not to correspond with the hormonal measurements. It is concluded that the resumption of pituitary and ovarian secretory functions post-partum is not always paralleled by a concomitant recovery of normal follicular growth and ovulation. Application of a progesterone threshold to judge resumption of ovulation post-partum should be reconsidered. PMID- 1500469 TI - Reliability of home urinary LH tests for timing of insemination: a consumer's study. AB - In this study, intrauterine insemination (IUI) was timed either after the detection of a urinary luteinizing hormone (LH) surge at home by the patient (group A), or following a positive LH test as interpreted by the gynaecologist (group B). Afterwards, samples tested by the patient were retested by the gynaecologist and vice versa. The gynaecologist also rechecked his own findings and the results were correlated with ultrasound data and charts of basal body temperature. Forty-seven cycles were evaluated. The patient's and the gynaecologist's readings agreed (+/- 12 h) in 42 of the cases (89%), and in five cycles (11%) a difference greater than 24 h was found. The intra-observer variation in the gynaecologist's results was +/- 12 h in four cycles (8.5%). These findings suggest that the LH test can be used as a reliable home device for the prediction of pending ovulation and timing of IUI. PMID- 1500470 TI - Induction of multiple follicular growth by pulsatile gonadotrophin-releasing hormone (GnRH) treatment in women with normal cycles: the role of the route of administration. AB - In a prospective study, seven patients with normal menstrual cycles were treated with pulsatile gonadotrophin-releasing hormone. They received one cycle of intravenous (i.v.) therapy and one cycle of subcutaneous (s.c.) therapy. Another four volunteers with normal cycles were treated for one s.c. cycle only. Cycles were compared to each other and to the normal unstimulated cycles of 14 other volunteers. Multiple follicular development could be achieved using both the i.v. and the s.c. routes. However, the i.v. route showed significantly higher luteinizing hormone (LH) and luteal steroid levels. Comparing s.c. cycles to controls, significantly lower LH levels were observed, resulting in significantly lower steroid production if calculated per large follicle. We conclude that the i.v. route is superior to the s.c. route in inducing multiple follicular growth in women with normal cycles. PMID- 1500471 TI - Luteal phase support and severe ovarian hyperstimulation syndrome. AB - The incidence and statistical associations of the ovarian hyperstimulation syndrome (OHSS) were studied in 304 egg retrievals with gonadotrophin-releasing hormone agonist suppression, gonadotrophin administration and follicular aspiration. In addition to preserving corpus luteum function, the luteal phase administration of human chorionic gonadotrophin (HCG) was associated with a higher incidence of severe OHSS than was supplementation with progesterone alone (12 versus 0%, P less than 0.001). Severe OHSS occurred in 3.7% and 12% of retrievals without and with pregnancy respectively (P less than 0.01). Stepwise logistic regression showed that the occurrence of moderate or severe OHSS was statistically predicted by the log of the serum oestradiol on the day the initial HCG was given (P less than 0.0001), treatment with luteal phase HCG (P less than 0.0003), and fetal number (P less than 0.0079). In the late luteal phase of cycles without luteal HCG, the serum oestradiol concentration was one-tenth and the serum progesterone concentration was one-fifth of the luteal phase value with HCG support (P less than 0.001). Without luteal phase HCG, oestradiol was two fold higher (P less than 0.001) and progesterone was 1.4-fold higher (P less than 0.005) in pregnant than in non-pregnant women. With luteal phase HCG, oestradiol was 1.4-fold higher in pregnant than in non-pregnant women (P less than 0.05), and progesterone was 1.7-fold higher (P less than 0.001). Oestradiol upper limits of 4400 and 14,700 pmol/l (1200 and 4000 pg/ml) for cycles with and without luteal phase HCG respectively correspond to approximately 5% risk of moderate or severe OHSS with a singleton pregnancy under these conditions. PMID- 1500472 TI - Human preovulatory follicular fluid: inhibin and free steroids related to optimal follicular maturation in ovarian stimulation regimes and possible function in ovulation. AB - Concentrations of inhibin, total and free oestradiol and progesterone were determined in preovulatory follicular fluid from 15 women undergoing in-vitro fertilization and embryo transfer treatment. The women underwent ovarian stimulation using clomiphene citrate and human menopausal gonadotrophin (HMG) (69 follicular fluid samples) in one cycle, and gonadotrophin-releasing hormone agonist (GnRHa) and HMG stimulation in the next treatment cycle (64 follicular fluid samples). The women thereby served as their own control. Inhibin, total oestradiol and progesterone were measured by radioimmunoassay. Concentrations of free steroid were calculated after quantitation of the steroid binding proteins, i.e. sex-hormone binding globulin (SHBG), cortisol binding protein (CBP) and albumin. Levels of inhibin and free and total progesterone were significantly higher in follicular fluids collected after stimulation with the GnRHa compared to the clomiphene regime (P less than 0.05, P less than 0.001, P less than 0.001, respectively). In contrast, levels of total and free oestradiol in follicular fluid were significantly lower after stimulation with GnRHa than after clomiphene stimulation (P less than 0.001). These results indicate that the follicles have achieved a more optimal maturation during the GnRHa regimen than during the clomiphene regime. It is suggested that the concentration of free biologically active steroids in follicular fluid, released into the peritoneal cavity during ovulation, may be physiologically important in stimulating the oviduct and the uterus in connection with ovulation, pre-embryo development and implantation. PMID- 1500473 TI - Clinical and endocrinological changes in women following ovulation induction using buserelin acetate/human menopausal gonadotrophin augmented with biosynthetic human growth hormone. AB - Biosynthetic human growth hormone added to an ovarian stimulation regime of human menopausal gonadotrophin (HMG) for IVF treatment improves the response of women who were previously resistant. This study investigated the efficacy of growth hormone (GH)/buserelin/HMG treatment in women with a previous normal response to buserelin/HMG stimulation. Ten patients (28-36 years, mean 32.5 years) were treated with GH (6 IU/day) plus buserelin/HMG. A control group of 10 women (28-37 years mean 31.0 years) received buserelin/HMG alone. All were given buserelin 500 micrograms and 2 ampoules (150 IU) HMG daily once pituitary suppression had been confirmed. There was no improvement in the GH group as assessed by follicular growth rate or number, oocyte number per woman and pregnancy rate. There was no effect of GH upon the serum oestradiol level and the follicular fluid levels of oestradiol, GH and inhibin. Serum IGF-1 increased significantly during GH administration, returning to pre-treatment levels 2 days after the last dose of GH. Follicular IGF-1 was much higher in the GH-treated group than the controls. Significant correlations were found in the GH-treated group between follicular fluid GH and follicular fluid oestradiol concentrations and between follicular GH and follicular size. Follicular IGF-1 was correlated with the serum IGF-1 concentration on day 8 of the GH/HMG treatment. In conclusion GH/buserelin/HMG treatment in women with a previous normal response to buserelin/HMG stimulation increased their serum and follicular IGF-1 concentrations. However, it does not improve the clinical ovarian response or the follicular secretion of oestradiol or inhibin. PMID- 1500474 TI - The detrimental influence of functional ovarian cysts during in-vitro fertilization cycles. AB - Reviewing 780 in-vitro fertilization (IVF) cycles, where buserelin was commenced in the preceding luteal phase and human menopausal gonadotrophin on day 4 of the ensuing menses, 53 cycles were identified with sonolucent cysts (30-50 mm diameter). Of the latter 53 cycles, the serum oestradiol was significantly greater on day 4 in 22 cycles abandoned for poor follicular development than in 31 cycles which proceeded to oocyte retrieval (P less than 0.05). Of the 31 cycles proceeding to oocyte retrieval, nine had a day 4 serum oestradiol greater than 200 pmol/l (95th centile for day 4 oestradiol in patients without apparent cysts), and these cycles produced significantly fewer grade 1 embryos than the cycles with day 4 oestradiol levels less than or equal to 200 pmol/l (P less than 0.05). Six of the 53 cycles with cysts resulted in conception, and all of these cycles had a day 4 serum oestradiol less than 200 pmol/l. Among the 53 cycles with ovarian cysts, the serum progesterone on the day of abandonment in four cycles and on the day of human chorionic gonadotrophin administration in one non abandoned cycle, was above the range established for 104 cycles without cysts. No significant difference was seen in day 4 serum androstenedione levels, and the day 4 serum progesterone was less than 5 nmol/l in all but one patient. Functional activity of ovarian cysts is associated with an adverse influence on IVF cycles. PMID- 1500475 TI - The significance of antisperm antibodies for sperm-cervical mucus interaction. AB - An overview is presented of the effects of antisperm antibodies on the sperm cervical mucus interaction. Antisperm IgA on spermatozoa or in cervical mucus can severely inhibit sperm penetration of cervical mucus and migration through it. Disturbance of the sperm-cervical mucus interaction is the only firmly established effect of these antisperm antibodies and leads to reduced fertility, as shown by a poor or negative result of the post-coital test. The presence of antisperm IgA in the male or female partner can be investigated more specifically with the sperm-cervical mucus contact test and can be confirmed by the sperm agglutination test on bromelinliquefied cervical mucus, by the mixed antiglobulin reaction test or by the immunobead test for IgA. PMID- 1500476 TI - Infertility treatment: relative effectiveness of conventional and assisted conception methods. AB - The effectiveness of infertility treatments is still questioned, particularly the assisted conception methods because of their complexity and cost. Furthermore, pregnancies often occur independent of treatment but many treatments have not been properly evaluated. The most basic audit of outcome with or without treatment requires pregnancy and preferably birth rates to be calculated in a cycle-specific and/or time-specific way; cumulative rates are the preferable method of calculation, in order to account for the usual tendency for fecundity to fall progressively. The choice of treatment usually depends on a balance of the chances of conceiving with or without treatment, and with more or less complicated treatments, and on other factors such as duration of infertility and the woman's age. This review aims to address those choices by assessing the actual and comparative effectiveness of treatments insofar as there are well defined and strictly comparable time-specific or cycle-specific published data available. Cumulative rates are described wherever possible and presented graphically for easy reference. PMID- 1500477 TI - Influence of number of pre-embryos transferred, progesterone level and oestradiol/progesterone ratio at thaw on pregnancy results during replacement of cryopreserved pre-embryos in natural cycles. AB - When frozen-thawed pre-embryos were transferred in a natural menstrual cycle, a clinical pregnancy rate of 22% per transfer cycle was obtained. The pregnancy rates were higher when serum progesterone levels at thaw were less than or equal to 3.4 ng/ml than when they were greater than or equal to 3.5 ng/ml. This was reflected in a significantly higher oestradiol/progesterone ratio at thaw in the conception cycles than in the non-conception cycles. PMID- 1500478 TI - A randomized prospective study comparing pregnancy rates following clomiphene citrate and human menopausal gonadotrophin therapy. AB - The anti-oestrogenic effect of clomiphene citrate causes an increased rate of associated cervical factor problems. Theoretically, it may also cause an adverse effect on the endometrium. The hostile mucus may be completely or partially corrected by the use of additional oestrogen after stopping clomiphene, or by intrauterine insemination (IUI). The prospective randomized study presented here was designed to determine whether a higher pregnancy rate might be achieved using human menopausal gonadotrophin (HMG) compared to clomiphene citrate. Thirty-seven women treated with clomiphene citrate for 165 cycles were compared to 33 treated with HMG for 179 cycles. A pregnancy was achieved in 81.1% of clomiphene-treated women (18.2%/cycle) versus 72.7% (13.3% per cycle) of HMG-treated women. The abortion rates of 13.3 and 12.5% respectively, were similar. The data suggest no adverse effect of clomiphene compared to HMG as far as pregnancy rates are concerned. IUI seems to be an effective means of treating cervical factor problems induced by clomiphene. PMID- 1500479 TI - Fallopian tube sperm perfusion used in a donor insemination programme. AB - Ninety-six couples were enrolled in a programme of Fallopian tube sperm perfusion (FSP). FSP is a method combining ovarian stimulation, ovulation induction and intra-uterine insemination with a 4 ml volume of sperm suspension. Frozen/thawed donor semen was used in all cycles. A total of 196 treatment cycles were started and of these 172 were completed. Twenty cycles were cancelled because of maturation of too many follicles, a low ovarian response, or formation of ovarian cysts. Five of the women enrolled in the programme did not have any inseminations. Forty-eight pregnancies occurred (27.9% per cycle) among 45 women (49.5%). There were five spontaneous abortions and one ectopic pregnancy. Sixteen pregnancies are on-going (greater than 12 weeks) and 26 women have delivered (including two sets of triplets and one set of twins). The pregnancy rate declined from the first attempt (34.1%) to the fourth attempt (14.3%). The pregnancy rate was significantly higher in women with three to five mature follicles compared to women with two or fewer mature follicles (P less than 0.05). Cycles in which human chorionic gonadotrophin (HCG) was administered on day 11 or later had a higher pregnancy rate than cycles where HCG was administered on day 10 (P less than 0.01). There was no difference in pregnancy rates between insemination with 8-10 x 10(6) motile spermatozoa and insemination with greater than 30 x 10(6) motile spermatozoa. FSP used in a programme of artificial insemination by donor using frozen/thawed donor semen is relatively simple to perform and gives a high pregnancy rate per cycle. PMID- 1500480 TI - Hormone and ultrasound parameters in ovarian stimulation cycles for direct intraperitoneal insemination. AB - To determine hormonal and ultrasound parameters associated with pregnancies, 115 women with unexplained infertility (n = 82), endometriosis (n = 22) or cervical factor (n = 11) were treated with direct intraperitoneal insemination (DIPI) after ovarian stimulation with clomiphene citrate and human menopausal gonadotrophins (HMG). Twenty women conceived and were compared with the remaining 95 non-pregnant women during one treatment cycle. Women with basal FSH levels less than or equal to 1.25 micrograms/l responded with higher oestradiol levels (P less than 0.0001), with the development of more follicles (P less than 0.05) and higher progesterone levels (P less than 0.05) than women with basal FSH levels greater than 1.25 micrograms/l, but the conception rates were similar. Women with miscarriages or biochemical pregnancies had a higher basal FSH value than both the women with term pregnancies and the non-pregnant women. Women with at least 3 preovulatory follicles greater than or equal to 15 mm had a higher pregnancy rate than those with fewer follicles, but a further increase was not observed above that number. The endometrium was thicker on the day of ovulation induction in cycles leading to a term pregnancy than in cycles without conception or with a biochemical pregnancy. No term pregnancy was observed when the endometrium was thinner than 8 mm. Women with a short luteal phase (less than 12 days) had a higher ratio of oestradiol/progesterone in the midluteal phase than women with a luteal phase of greater than or equal to 12 days and pregnant women.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1500481 TI - Endometriosis: a new approach is needed. AB - Endometriosis is generally regarded and treated as an endocrine and/or a surgical disease. Endocrine and surgical approaches to treatment are effective only in treating the symptoms of the disease and not its pathophysiology. Consequently, the success of such therapy is at best short-lived, and probably non-existent in mild disease. This thesis therefore argues for a new therapeutic approach towards endometriosis. In view of increasing evidence in favour of an immunological aetiology for this condition, it is suggested that such an approach may involve immunological rather than endocrine manipulation. It is also proposed that so called unexplained infertility may in many cases represent a precursor stage of endometriosis, since immunological abnormalities in both of these conditions are so similar. Large-scale, prospective, multicentre clinical trials of immunotherapy in unexplained infertility and endometriosis appear to be indicated at this time if endometriosis is to lose its importance as one of the major contributors to female infertility. PMID- 1500482 TI - Meiotic segregation of a 21;22 Robertsonian translocation. AB - In-vitro fertilization of hamster oocytes with human spermatozoa has been used to study heterozygotes for structural chromosome abnormalities. To date only four men heterozygous for Robertsonian translocations have been examined. In this study, 150 sperm chromosome complements from a 21;22 translocation were investigated. There was no evidence of an interchromosomal effect since the frequency of abnormalities unrelated to the translocation was within the range of normal donors. The frequency of unbalanced complements was 3.4%, which is similar to other Robertsonian translocations. As expected, an equivalent number of normal (n = 74) and balanced (n = 70) karyotypes was observed. PMID- 1500483 TI - A new sperm collection method for in-vitro fertilization: collection at tail of epididymis. AB - We have developed a method for the collection of spermatozoa from the tail of the epididymis in patients with severe asthenozoospermia. The treatment was applied to 25 cycles, of which 16 cycles provided spermatozoa in good condition with concentration and motility greater than 50 x 10(4)/ml and greater than 50% respectively. Spermatozoa thus obtained were subjected to IVF in 11 cycles and to ZIFT in five cycles; five IVF cases reached cleavage and two of those cases resulted in pregnancy. Two of the five ZIFT cases also achieved a pregnancy. Despite limits on frequency, the sperm collection process is thought to be very useful for the treatment of severe asthenozoospermia. PMID- 1500484 TI - Perforated appendicitis following transvaginal oocyte retrieval for in-vitro fertilization and embryo transfer. AB - A case of appendicitis following transvaginal oocyte retrieval is presented. The time sequence and the finding of puncture holes in the appendix indicate a causal relationship between the two events. Although minor infectious complications have been reported previously, this is the first report of appendicitis caused by transvaginal oocyte retrieval. PMID- 1500485 TI - The effects of human skin fibroblast monolayers on human sperm motility and mouse zygote development. AB - A new system for co-culture in human in-vitro fertilization (IVF), using human skin fibroblasts, is described and tested pre-clinically. The first test involved the development of 1-cell mouse embryos which exhibit the 2-cell developmental block in vitro. Passage through this block (pb1-ratio) was determined by the ratio of compacted morula stages on day 4 of incubation. For nine human skin cell lines tested (fetal, neonatal and adult), the pb1-ratio was approximately 0.45 (0.07 in culture medium alone; P less than 0.0005). At the compacted morula stage, a second developmental block was observed. The ratio of passing this block (pb2-ratio) was 0.70 +/- 0.09 on skin fibroblasts obtained from fetal or neonatal tissue. On fibroblasts from adult patients the pb2-ratio was 0.30 +/- 0.04 (P less than 0.0005). The second test examined the influence of skin fibroblasts from fetal or neonatal tissue on human sperm motility. After 24 h of incubation, all skin cell lines had a positive influence (P less than 0.01) on the percentage motility compared to culture medium alone. The curvilinear velocity was not significantly increased. From the results we conclude that (i) human skin fibroblasts (especially from fetal tissue) have a positive influence on the development of mouse embryos in vitro, (ii) there is a positive influence of human skin fibroblasts on the percentage motility of human spermatozoa, and (iii) a clinical trial of co-culture with human skin fibroblasts can be justified. PMID- 1500486 TI - The influence of slow and ultra-rapid freezing on the organization of the meiotic spindle of the mouse oocyte. AB - We have investigated the effect of ultra-rapid versus slow freezing on the meiotic spindle of the mouse oocyte. A slow freezing protocol [1.5 M dimethyl sulphoxide (DMSO)] and an ultra-rapid protocol (3.5 M DMSO/0.5 M sucrose) have been compared. Oocytes were fixed at different time points as follows: after prefreeze equilibration, immediately after thawing and after 60 or 180 min of post-thaw recuperation. The spindle was visualized with a monoclonal anti-alpha tubulin antibody followed by an immunogold-silver staining technique. The chromosomes were stained with 4',6-diamidino-2-phenylindole (DAPI). Spindle morphology was classified as follows: normal barrel-shaped, abnormal shaped, partial/multipolar or absent. After slow freezing with 1.5 M DMSO, these spindle morphologies were found respectively in 67%, 17%, 11% and 6% of the oocytes after 60 min of post-thaw recuperation and in 72%, 11%, 11% and 6% after 180 min. After ultra-rapid freezing with 3.5 M DMSO/0.5 M sucrose, we observed the same categories of spindle morphology in 84%, 13%, 3% and 0% of oocytes after 60 min of post-thaw recuperation and in 86%, 7%, 7% and 0% after 180 min. The present study demonstrates that the majority of spindles exhibit a normal morphology after both slow and ultra-rapid freezing. The ultra-rapid freezing protocol preserved spindle integrity to the highest extent. Nevertheless, the occurrence of abnormal spindles and chromosome dislocation indicate that the genetic risk of oocyte freezing has to be evaluated in further detail. PMID- 1500487 TI - Structural heterogeneity of platelet-activating factor produced by murine preimplantation embryos. AB - Platelet-activating factor (PAF) is 1-O-alkyl-2-acetyl-sn-glycero-3 phosphocholine with the alkyl moiety predominantly a mixture of saturated hexadecyl and octadecyl chains (C16:0 and C18:0 PAF, respectively). Previously, a PAF bioassay was compared with a radioimmunoassay for PAF (NEN Du Pont). Both assays were sensitive and quantitative, but the correlation between PAF measured by the bioassay compared to the radioimmunoassay was poor for murine embryo derived PAF (r = 0.773, n = 88), while being completely adequate (r = 0.961) for a PAF standard which was an equimolar mixture of C16:0 and C18:0 PAF (C16:0/C18:0 PAF). This study compared a larger sample size of murine embryo-derived PAF (n = 154) and found that the poor correlation between the two assays persisted (r = 0.791). When dose-response curves were generated with C16:0, C16:0/C18:0 and C18:0 PAF (over a concentration range of 0.3-30 ng/ml), the concentrations which gave a 50% response were equivalent in the bioassay (i.e. 6 ng/ml), but differed in the radioimmunoassay (i.e. 1.5, 3 and 6 ng/ml, respectively). Following separation of murine embryo-derived PAF (from medium in which 30 two-cell embryos had been cultured for 24 h) into C16:0 and C18:0 PAF by reverse phase high performance liquid chromatography, 9/20 cultures produced 100% C16:0 PAF, 2/20 cultures produced 100% C18:0 PAF and the remaining 9/20 cultures produced varying proportions of both.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1500488 TI - Pretreatment of hamster oocytes with Ca2+ ionophore to facilitate fertilization by ooplasmic micro-injection. AB - The fertilization rate after ooplasmic micro-injection in mammals is low. In hamsters, micro-injection of sperm nuclei into oocytes resulted in the release of the second polar body and the formation of female and male pronuclei, but disappearance of the cortical granules was minimal. These unfavourable results seem to be associated with insufficient activation of oocytes by the current techniques of micro-injection. Therefore, we attempted to increase the fertilization rate by pretreating the oocytes with a Ca2+ ionophore, A23187 (10 microM, 3 min). Sperm nuclei were then micro-injected into the treated oocytes and 5 h later the percentage of oocytes at the pronuclear stage was examined: 53.1% for untreated controls and 85.7% for the treated group (P less than 0.05). However, when the number of pronucleate oocytes was divided by the number of A23187-activated oocytes, the percentage was 81.0% for the controls and 85.7% for the treated group. These findings suggest that pretreatment of oocytes with ionophore does not facilitate fertilization of activated oocytes, but that it indirectly enhances their development to the pronuclear stage by increasing the efficiency of egg activation. PMID- 1500489 TI - Patterns of expression of integrin molecules in human endometrium throughout the menstrual cycle. AB - A heterogeneous group of cells interact with each other and with the surrounding matrix to form the complex structure of human endometrium. Since the integrin superfamily of molecules is involved in the cell-cell and cell-matrix interactions, this study was designed to screen, in situ, the cellular distribution of CDW49a-f molecules in human endometrium throughout the menstrual cycle. The integrin molecules were localized by immunohistochemistry using monoclonal antibodies. Glandular epithelium expressed all integrin molecules. With the exception of CDW49d (alpha 4 beta 1), surface epithelium also expressed all these molecules. Endothelial cells were positive for all integrin molecules except CDW49a (alpha 1 beta 1). Endometrial lymphoid cells were positively immunostained for CDW49a, d and e (alpha 5 beta 1) and were negative for CDW49b (alpha 2 beta 1), CDW49c (alpha 3 beta 1) and CDW49f (alpha 6 beta 1). Regional differences in the expression of integrin molecules were observed. As compared to the functionalis epithelium, basalis epithelium characteristically exhibited higher expression of CDW49a, d and e. Two integrins in endometrium, CDW49a and d exhibited changes related to the menstrual cycle. CDW49a, which was not expressed in glandular epithelial cells in the proliferative phase, was strongly expressed in these cells after ovulation and its expression was diminished in the late secretory phase. This molecule was not expressed in the stromal cells, however, predecidual cells characteristically expressed this molecule in the late secretory phase. CDW49d was only expressed in the glandular epithelial cells in the mid-proliferative to mid-secretory phases.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1500490 TI - Turner's syndrome patients lack tight junctions between uterine epithelial cells. AB - Eleven endometrial biopsies, taken from six Turner's syndrome patients receiving hormone replacement therapy prior to treatment by oocyte donation and embryo transfer, were assessed by freeze fracture followed by electron microscopy for epithelial tight junctions. Nine of the eleven biopsies had no discernible tight junctions; the other two biopsies had reduced and disorganized junctional structures. Two patients subsequently became pregnant following embryo transfer. It is concluded that compromised epithelial integrity does not prevent embryo implantation in the human, an observation that is consistent with a barrier role for the epithelium except at times when appropriately conditioned with oestrogen and progesterone to induce receptivity for implantation. PMID- 1500491 TI - Treatment of moderate and severe hirsutism with a gonadotrophin-releasing hormone agonist. PMID- 1500492 TI - Serological responses to various Coccidioides antigen preparations in a new enzyme immunoassay. AB - A new enzyme immunoassay (EIA) was used to investigate immunoglobulin M (IgM) and IgG responses to various coccidioidal antigen preparations. Direct binding and inhibition assays both revealed that the IgG responses of many serum specimens were directed largely to the tube precipitin (TP) antigen even when the microwells were coated with a combination of coccidioidal antigens (CCAs). From a panel of 28 serum specimens containing antibodies to CCAs, 4 serum specimens yielded high IgG signals (absorbance, greater than 1.0) and were negative for IgM (absorbance, less than 0.2), yet all four IgG responses were inhibited by at least 90% with partially purified TP antigens (2.4 micrograms/ml). The IgM and IgG fractions of several serum specimens were separated by ion-exchange chromatography and assayed by using different antigen preparations adsorbed to the microwells. The binding of both IgM and IgG peaks to the microwells coated with the CCA preparation was inhibited significantly by preincubation with TP antigens. One serum specimen (specimen 26) yielded a large IgG response (absorbance, greater than 2.0) with the CCA preparation and also bound directly to microwells coated only with TP antigens. The IgG signal (absorbance) of serum specimen 26 was reduced by 98% when it was preincubated with TP antigens prior to the assay. Significant IgG signals from several other serum specimens were observed when microwells were coated with TP antigen preparations, but they were absent when periodate-treated preparations were used. Two cerebrospinal fluid specimens yielded IgG signals with CCA-coated microwells, which were not inhibited by TP antigens, and yielded no signal with microwells coated only with TP antigens. The results are consistent with the concept that the typical serologic response to TP antigens occurs early in disease progression, but they suggest that TP antigens stimulate both IgM and IgG responses. PMID- 1500493 TI - Direct detection of hepatitis B virus from dried blood spots by polymerase chain reaction amplification. AB - The presence of hepatitis B virus DNA in the sera of individuals is the most definitive marker of an active viral infection. We have used polymerase chain reaction detection of hepatitis B virus DNA directly on whole blood dried as a spot on filter paper. The method is rapid, specific, and sensitive and has the ability to detect as little as 10 virus particles by ethidium bromide staining of the polymerase chain reaction-amplified products. The method is cost-effective, and the stability of the spots makes the collection and transportation of potentially infectious blood safe. PMID- 1500494 TI - Laboratory and clinical evaluations of media for the primary isolation of Haemophilus species. AB - There has not previously been an objective comparison of medium formulations for the primary isolation of Haemophilus species. This study was undertaken to evaluate the components required for the optimal growth of large, easily identifiable colonies of these bacteria. We compared six medium bases and seven supplements for their ability to support the growth of 86 strains of Haemophilus influenzae and 17 strains of other species of Haemophilus. By using a growth index that combines colony size and the dilution factor, a formulation of GC agar base with 1% yeast autolysate and 5% sheep blood (chocolated) promoted the growth of large, easily recognizable colonies of H. influenzae and other Haemophilus species. This medium was designated GCYSB. The addition of hematin to supplements that supplied NAD (or factor V) to the medium was inhibitory to the growth of all of the Haemophilus species tested. In a clinical comparison of GCYSB with routinely used chocolate agar medium in two laboratories for the primary isolation of Haemophilus species, overall GCYSB promoted better growth of 124 strains of H. influenzae and H. parainfluenzae. GCYSB is easy to prepare and inexpensive compared with the ease of preparation and expense of other Haemophilus isolation media. PMID- 1500495 TI - Development of polymerase chain reaction assays for detection of Listeria monocytogenes in clinical cerebrospinal fluid samples. AB - In order to improve the diagnosis of Listeria meningitis or meningoencephalitis, especially in patients who have received antibiotics before their cerebrospinal fluid (CSF) has been examined, two assays for the detection of Listeria monocytogenes based on the polymerase chain reaction (PCR) were evaluated. After a standard PCR, the amplified DNA was detected either by a second round of PCR with internal primers followed by gel electrophoresis and ethidium bromide staining (nested PCR) or by dot blot hybridization to an internal digoxigenin labeled probe (PCR-dot blot). For PCR, two sets of primers within the invasion associated protein gene (iap gene) were chosen. They allowed for the highly specific detection of all L. monocytogenes reference strains tested (serotypes 1/2a, 1/2b, 1/2c, 3a, 3b, 3c, 4a, 4b, 4c, 4d, and 7). These primers did not detect amplification products from various other gram-positive or gram-negative bacterial DNAs or human DNA. The sensitivities of both assays were assessed on sterile CSF samples that were artificially seeded with serial dilutions of L. monocytogenes serotype 4b cells. By both methods the limit of detection was less than 10 cells in the initial reaction. Since the nested PCR is more prone to contamination because of manipulation of the amplified products, a standard PCR assay followed by dot blot hybridization was applied to 52 CSF samples in a retrospective study. Of 28 CSF samples which were sterile or positive for bacteria other than Listeria species, 24 were PCR negative. In contrast, from 17 patients with culture-proven Listeria meningitis, 14 of 17 initial CSF samples were PCR positive, as were 3 of 7 culture-negative followup CSF samples taken after patients received antibiotics. These results support the usefulness of this approach in the diagnosis of Listeria meningitis, in particular, when antibiotic administration precedes culture of CSF. PMID- 1500496 TI - Polymerase chain reaction-gene probe detection system specific for pathogenic strains of Yersinia enterocolitica. AB - The polymerase chain reaction technique was used to develop a rapid diagnostic assay for detection of pathogenic Yersinia enterocolitica strains. The assay targeted a stretch of 163 bp of the yst gene and could be applied to both pure cultures and crude DNA extracted from feces. The defined primer pair amplified the targeted sequence from only pathogenic strains and fecal samples seeded with the serotype O:3 strain of Y. enterocolitica, whereas neither nonpathogenic strains nor normal stools yielded any amplified fragments. Of the other Yersinia species and non-Yersinia species tested, only two strains of Y. kristensenii yielded the same amplified product. A 20-mer oligonucleotide probe specifically hybridized within the amplified yst fragment of Y. enterocolitica but did not hybridize with the amplified yst fragment of Y. kristensenii by Southern and dot blot hybridizations. This confirms the reliability of this diagnostic assay in both clinical and epidemiological studies. The availability of the extracted DNA for the polymerase chain reaction was checked by simultaneous amplification of a part of the 16S rDNA and the yst gene. The entire diagnostic assay, including a simplified technique for DNA extraction, the amplification process, and gel electrophoresis, could be completed within 1 working day, which is better than the time required for the time-consuming traditional techniques used in clinical laboratories. PMID- 1500497 TI - Staphylococcus lugdunensis endocarditis. AB - Staphylococcus lugdunensis is a recently described coagulase-negative species which has been associated with human infections, including infective endocarditis. A case of native valve endocarditis caused by this organism is described. The initial laboratory detection of S. lugdunensis is facilitated by a positive test for ornithine decarboxylase. The identification of such isolates should not cause difficulty unless undue reliance is placed upon a small number of tests. PMID- 1500498 TI - Epidemiology of Enterococcus faecalis urinary tract infection in a teaching hospital in London, United Kingdom. AB - Enterococcus faecalis is a frequent cause of urinary tract infection in hospitalized patients. Recent reports have suggested that the organism may frequently be acquired by cross-infection from other patients. In this study, we used total DNA restriction patterns to type 135 urine isolates of E. faecalis from four sets of patients. Isolates were placed into types (all bands identical) and into groups (most bands identical). Most isolates were discriminated by the typing method, and the results suggested that direct cross-infection occurred rarely if at all. However, two groups of clonally related isolates occurred frequently in the urine specimens and also in feces from hospital-associated patients and were often associated with antibiotic resistance. Isolates from these two groups were found less frequently in feces from people not associated with the hospital. PMID- 1500499 TI - Primary humoral antibody response to Coxiella burnetii, the causative agent of Q fever. AB - Of 147 patients with acute Q fever diagnosed during a major outbreak in Birmingham, England, in early summer 1989, 41 provided sets of sera which allowed us to make a detailed analysis of the primary humoral immune response. Antibody titers specific for Coxiella burnetii were measured by the complement fixation test and by an immunoglobulin M (IgM)- and IgG-specific indirect immunofluorescence test. The relative avidity of specific IgGs was determined by the indirect immunofluorescence test with and without treatment of antigen antibody complexes with 8 M urea. The IgG subclass responses after primary infection and their avidities were also determined for a limited number of paired serum specimens. Specific IgM titers persisted for more than 6 months in the majority of cases and were therefore not a sufficient criterion for the diagnosis of recent infection. However, for serial samples the antibody titer ratios (IgG/IgM) and the ratios (IgG titer with treatment/IgG titer without treatment) that indicated relative avidity changed significantly, depending on the time postinfection. Within the IgG class, the C. burnetii-specific antibody response over time was almost exclusively represented by subclass 1 molecules, which thus showed affinity maturation. PMID- 1500500 TI - Use of HEp-2 cells for improved isolation and passage of Chlamydia pneumoniae. AB - Chlamydia pneumoniae has proved to be difficult to isolate and propagate in cell culture. We compared the growth of three strains of C. pneumoniae, TW-183 and two clinical isolates from Brooklyn, N.Y., in five cell lines, including HeLa 229, McCoy, HL, HEp-2, and HTED, an immortalized human tracheal cell line. HEp-2 was the most sensitive cell line tested. When 10-fold dilutions of three C. pneumoniae strains at known titers were inoculated into the different cell lines, the mean number of inclusion-forming units per milliliter was 1 to 2 log units higher in the HEp-2 than in the other cell lines. This difference was statistically significant. Omission of pretreatment with DEAE-dextran resulted in larger inclusions than those seen in pretreated cells, with the exception of McCoy and HTED cells. Retrieval of clinical specimens previously cultured on HeLa 229 cells and comparison of mean inclusion counts in fresh clinical specimens simultaneously inoculated on HeLa 229 and HEp-2 cells suggested that culture in HEp-2 cells may require only the initial inoculation and one passage, compared with three to four passages, as required by culture in HeLa 229 cells. PMID- 1500501 TI - Characterization of a distinct group of slowly growing mycobacteria by biochemical tests and lipid analyses. AB - A group of slowly growing mycobacterial strains (n = 14) isolated from respiratory tract specimens was collected from 1971 to 1990 on the basis of growth characteristics and uncommon biochemical and glycolipid profiles. Growth at 25 to 45 degrees C, a negative Tween 80 hydrolysis test, a strong positive reaction in a 14-day arylsulfatase test, and susceptibility to ethambutol in combination with resistance to cycloserine were important for the initial separation. The strains had a distinctive glycolipid pattern which was unlike those of other mycobacterial species. Analyses of cellular fatty acids by gas liquid chromatography and mycolic acids by thin-layer chromatography further characterized this homogeneous group of mycobacteria. The presence of 2-eicosanol (2-OH-20:0alc) and hexacosanoic acid (26:0) combined with the lack of 2-docosanol (2-OH-22:0alc) differentiated this group from other slowly growing mycobacteria. PMID- 1500502 TI - Collaborative investigation of broth microdilution and semisolid agar dilution for in vitro susceptibility testing of Candida albicans. AB - A study was performed in two laboratories to evaluate the effect of growth medium and test methodology on inter- and intralaboratory variations in the MICs of amphotericin B (AMB), flucytosine (5FC), fluconazole (FLU), itraconazole (ITRA), and the triazole Sch 39304 (SCH) against 14 isolates of Candida albicans. Testing was performed by broth microdilution and semisolid agar dilution with the following media, buffered to pH 7.0 with morpholinepropanesulfonic acid (MOPS): buffered yeast nitrogen base (BYNB), Eagle's minimal essential medium (EMEM), RPMI 1640 medium (RPMI), and synthetic amino acid medium for fungi (SAAMF). Inocula were standardized spectrophotometrically, and endpoints were defined by the complete absence of growth for AMB and by no more than 25% of the growth in the drug-free control for all other agents. Comparative analyses of median MICs, as determined by each test method, were made for all drug-medium combinations. Both methods yielded similar (+/- 1 twofold dilution) median MICs for AMB in EMEM and RPMI, 5FC in all media, and FLU in EMEM, RPMI, and SAAMF. In contrast, substantial between-method variations in median MICs were seen for AMB in BYNB and SAAMF, FLU In BYNB, and ITRA and SCH in all media. Interlaboratory concordance of median MICs was good for AMB, 5FC, and FLU but poor for ITRA and SCH in all media. Endpoint determinations were analyzed by use of kappa statistical analyses for evaluating the strength of observer agreement. Moderate to almost perfect interlaboratory agreement occurred with AMB and 5FC in all media and with FLU in EMEM, RPMI, and SAAMF, irrespective of the test method. Slight to almost perfect interlaboratory agreement occurred with ITRA and SCH in EMEM, RPMI, and SAAMF when tested by semisolid agar dilution but not broth microdilution. Kappa values assessing intralaboratory agreement between methods were high for 5FC in all media, for AMB in BYNB, ENEM, and RPMI, and for FLU in EMEM, RPMI, and SAAMF. One laboratory, but not the other, reported substantial to almost perfect agreement between methods for ITRA, and SCH in EMEM, RPMI, and SAAMF. Both laboratories reported poor agreement between methods for the azoles in BYNB. Discrepancies noted in azole-BYNB combinations were largely due to the greater inhibitory effect of these agents in BYNB than in other media. These results indicate that the semisolid agar dilution and broth microdilution methods with EMEM or RPMI yield equivalent and reproducible MICs for AMB, 5FC, and FLU but not ITRA and SCH. PMID- 1500503 TI - Pulsed-field gel electrophoresis for epidemiologic studies of Campylobacter hyointestinalis isolates. AB - Campylobacter hyointestinalis was isolated from five members of the same family who had previously consumed raw milk. Pulsed-field gel electrophoresis of genomic DNAs from the five strains, after digestion with restriction endonuclease SalI, revealed that three strains had identical genome patterns and therefore appeared to be related, whereas the other two had completely different genome patterns and appeared to be unrelated. We report here for the first time the isolation of C. hyointestinalis from family members who had consumed raw milk. Our study also demonstrates the usefulness of pulsed-field gel electrophoresis for epidemiologic studies of this unusual campylobacter. PMID- 1500504 TI - Evaluation of commercial and standard methodology for determination of oxacillin susceptibility in Staphylococcus aureus. AB - Agar dilution with and without 4% NaCl, broth microdilution with 2% NaCl, the dried MicroScan Rapid Positive MIC 1 panel (Baxter Health Care Corp., West Sacramento, Calif.), the Vitek GPS-SA card (Vitek Systems, Hazelwood, Mo.), and the oxacillin agar screen plate were compared with a DNA probe encoding the mec gene for their abilities to detect oxacillin resistance in 506 clinical isolates of Staphylococcus aureus. The results of testing for the mec gene showed that there were 254 oxacillin-resistant and 252 oxacillin-susceptible isolates of S. aureus. There were 14.2% very major errors with Vitek (a resistant isolate was interpreted as susceptible) and 6.7% very major errors with MicroScan. Fewer major errors were seen: 0.8% with MicroScan (a susceptible isolate was interpreted as resistant) and 0.4% with Vitek. No very major errors but 2.4% major errors occurred by agar dilution with 4% NaCl supplementation, whereas there were 0.8% very major and 0.4% major errors without 4% NaCl supplementation. By broth microdilution there were 2.0% very major and 0.8% major errors. The results of the oxacillin agar screen plate method were 100% concordant with those of the mec gene probe method. PMID- 1500505 TI - BioArgos: a fully automated blood culture system. AB - BioArgos (Sanofi Diagnostics Pasteur, Marnes-la-Coquette, France) is a fully automated blood culture system that detects carbon dioxide production by infrared spectroscopy through a glass bottle. This hands-off system was compared with the BACTEC NR-660 system (Becton Dickinson Diagnostic Instrument Systems, Towson, Md.). A total of 336 microorganisms belonging to 74 taxa were tested in simulated blood cultures by both systems. Experimental data showed no significant differences between the two systems. The inclusive detection times (+/- the standard deviations) were 33.2 +/- 28.7 and 35.0 +/- 30.6 h with BioArgos and BACTEC, respectively. Anaerobes were detected earlier with BioArgos, whereas detection of some organisms that need oxygen to grow was slightly delayed. In conclusion, BioArgos is as reliable and accurate as BACTEC NR-660 and shows better practicability owing to noninvasive detection, reduction of vial manipulation, and absence of daily maintenance. PMID- 1500506 TI - Application of ubiquinone systems and electrophoretic comparison of enzymes to identification of clinical isolates of Aspergillus fumigatus and several other species of Aspergillus. AB - The ubiquinone systems and electrophoretic comparison of enzymes were used to determine the relatedness among 64 isolates of seven Aspergillus spp. These were 31 clinical and 3 nonclinical isolates of Aspergillus fumigatus Fres., 2 isolates of A. nidulellus Samson & W. Gams, 8 isolates of A. terreus Thom, 4 isolates of A. flavus Link, 1 isolate of A. oryzae (Ahlburg) Cohn, 14 isolates of A. niger van Tieghem, and 1 isolate of A. japonicus Saito. The enzymes glucose 6-phosphate dehydrogenase, lactate dehydrogenase, glutamate dehydrogenase, fumarase, and malate dehydrogenase were examined. The relative mobilities were analyzed numerically. The results were presented as a dendrogram. Isolates from clinical and nonclinical sources within the same species had identical ubiquinone systems and identical or very similar enzyme patterns. In the dendrogram, 64 of the tested isolates were separated into seven major clusters at a 60% similarity level. Each major cluster corresponds to a single species. On the dendrogram, A. fumigatus isolates showed homogeneity, whereas A. niger isolates showed relative heterogeneity; in particular, A. niger MF-24 and the other A. niger isolates were distantly linked to each other. All A. fumigatus isolates had the Q-10 ubiquinone system and formed a single major cluster at a similarity level of 73% or greater. Glucose 6-phosphate dehydrogenase and glutamate dehydrogenase were key enzymes for differentiating all clinical and nonclinical isolates of A. fumigatus from the other Aspergillus spp. Ubiquinone systems and enzyme patterns appear to be objective and useful indicators for use in the precise identification of clinical isolates of Aspergillus spp. PMID- 1500507 TI - Immunoglobulin A (IgA) and IgG serum antibodies to mycobacterial antigens in Crohn's disease patients and their relatives. AB - Sera from patients with Crohn's disease, their relatives, their spouses, and unrelated healthy controls were assayed by enzyme-linked immunosorbent assay for immunoglobulin G (IgG) and IgA antibodies to Mycobacterium tuberculosis, M. avium, and M. gordonae. The patients had significantly higher IgA responses to mycobacterial antigens than did either their relatives or the controls. On the other hand, both the patients and their relatives had significantly higher IgG responses against these antigens than did the controls. The elevated IgA response was more pronounced against isopentanol-extracted whole bacterial cells than it was against soluble protein extracts, and it appeared to be directed against fixed surface antigens that lie under the loosely bound peptidoglycolipid or glycolipid antigens of mycobacteria. PMID- 1500508 TI - Standardization of an enzyme immunoassay for human antibody to Haemophilus ducreyi. AB - We standardized a serologic enzyme immunoassay (EIA) for human immunoglobulin G and M antibodies against Haemophilus ducreyi. We evaluated the performance of this test with respect to the time from acute chancroid and coinfection with human immunodeficiency virus (HIV). Antibody to a crude, soluble bacterial antigen of one H. ducreyi strain was detected in a panel of serum samples from clinically and microbiologically confirmed cases of chancroid and from controls. Test interpretation was standardized for optimal sensitivity and specificity. Performance of the EIA was enhanced in the period of early convalescence from acute primary chancroid and was not diminished in the presence of HIV coinfection. The EIA performed adequately as a serologic screening test for field evaluation and epidemiologic application in conjunction with sexually transmitted disease and HIV detection and control efforts. PMID- 1500509 TI - Detection and identification of mycobacteria by amplification of a segment of the gene coding for the 32-kilodalton protein. AB - A polymerase chain reaction (PCR) assay for the rapid detection of mycobacterial DNA is described. Oligonucleotide primers, derived from the sequence of a gene coding for the 32-kDa antigen of Mycobacterium tuberculosis, amplified DNA from all 28 species of mycobacteria tested. All nonmycobacterial species tested were negative. An oligonucleotide probe hybridized to the PCR products of the strains belonging to the M. tuberculosis complex. This method could detect as little as 50 fg, as tested with purified M. tuberculosis DNA. By this amplification method, 127 sputum specimens were tested, with 7.9% of the specimens proving to be inhibitory in PCR. The sensitivity of detection by PCR compared with that by culture was 55.9%; when the inhibitory specimens were excluded, the sensitivity was 70.4%. The specificity of PCR combined with hybridization was 100%. PMID- 1500510 TI - Development of revised quality control limits for disk diffusion susceptibility tests of selected cephem antibiotics with Haemophilus influenzae and description of a new control strain. AB - Inconsistent quality control results in disk diffusion testing of cefaclor, cefamandole, cefonicid, and cefuroxime with Haemophilus influenzae ATCC 49247 and Haemophilus test medium (HTM) prompted a search for an alternative control strain that would provide more reliable results. A five-laboratory study was conducted to evaluate two candidate H. influenzae strains as possible alternatives to the aforementioned strain. Repetitive testing of the candidate strains and H. influenzae ATCC 49247 over several days with a total of six different lots of HTM documented consistent performance of the two candidate strains and confirmed inconsistent results for some of the antibiotics with H. influenzae ATCC 49247. In particular, certain lots of HTM failed to yield cefaclor and cefamandole zone sizes within the quality control range advocated by the National Committee for Clinical Laboratory Standards. Because of the greater consistency offered by the new strains, one was selected (now designated H. influenzae ATCC 49766) to be recommended for routine quality control testing of cefaclor, cefamandole, cefonicid, cefuroxime, and the related carbacephem loracarbef. The new control strain and zone size ranges proposed here have been approved by the National Committee for Clinical Laboratory Standards in place of the previously recommended strain and zone size limits for testing of these five cephem antibiotics. PMID- 1500511 TI - Haemophilus influenzae ATCC 49766, an alternative quality control strain for monitoring broth microdilution susceptibility tests with selected beta-lactams. AB - A beta-lactamase-negative, ampicillin-resistant strain of Haemophilus influenzae is currently used for quality control of broth microdilution tests performed with Haemophilus test medium (HTM). Studies with eight lots of HTM broth documented the fact that MIC limits for some antimicrobial agents are unrealistically stringent; i.e., only three of eight lots of HTM broth were satisfactory for testing cefaclor. An alternative, ampicillin-susceptible strain of H. influenzae (ATCC 49766) was found to provide much more reproducible results with five problematic drugs (cefaclor, cefuroxime, cefamandole, loracarbef, and cefonicid). Multilaboratory studies defined MIC control limits for both control strains tested against 12 antimicrobial agents. PMID- 1500512 TI - Laboratory diagnosis of Clostridium difficile-associated gastrointestinal disease: comparison of a monoclonal antibody enzyme immunoassay for toxins A and B with a monoclonal antibody enzyme immunoassay for toxin A only and two cytotoxicity assays. AB - A total of 320 stool specimens obtained from 262 patients suspected of having Clostridium difficile-associated gastrointestinal disease were examined with two cytotoxicity assays (CTAs) and two commercially available enzyme immunoassays (EIAs). The CTAs were an in-house-developed procedure (University of Massachusetts Medical Center [UMMC], Worcester, Mass.) and a commercial test (Bartels CTA; Baxter Healthcare Corp., West Sacramento, Calif.). One EIA was a monoclonal antibody-based assay for C. difficile toxins A and B (Cambridge Biotech Corp. [CBC], Worcester, Mass.). The other EIA employed monoclonal antibodies directed against only toxin A (Meridian Diagnostics, Cincinnati, Ohio). True-positive and true-negative results were defined on the basis of the results of the four assays, clinical assessments of patients, and the results of other laboratory tests. The sensitivities of the four assays were as follows: Bartels CTA, 100%; UMMC CTA, 97.2%; CBC EIA, 84.5%; and Meridian EIA, 69.0%. The Bartels CTA demonstrated a specificity of 99.2%. The other three assays had a specificity of 100%. PMID- 1500513 TI - Clonal analysis of methicillin-resistant Staphylococcus aureus strains from intercontinental sources: association of the mec gene with divergent phylogenetic lineages implies dissemination by horizontal transfer and recombination. AB - Genetic relationships among 254 isolates of Staphylococcus aureus resistant to methicillin recovered between 1961 and 1992 from nine countries on four continents were determined by analyzing electrophoretically demonstrable allelic variation at 15 chromosomal enzyme loci. Fifteen distinctive electrophoretic types, marking clones, were identified. The mec gene is harbored by many divergent phylogenetic lineages representing a large portion of the breadth of chromosomal diversity in the species, a result that is interpreted as evidence that multiple episodes of horizontal transfer and recombination have contributed to the spread of this resistance determinant in natural populations. Isolates recovered in the United Kingdom, Denmark, Switzerland, Egypt, and Uganda in the 1960s are of a single multilocus enzyme genotype and probably are progeny of an ancestral methicillin-resistant clone. There is geographic variation in the frequency of recovery of the common methicillin-resistant clones, an observation that may in part explain reported regional differences in natural history correlates of resistant organisms. PMID- 1500514 TI - Rapid whole-blood microassay using flow cytometry for measuring neutrophil phagocytosis. AB - A simple flow cytometric method (FCM) for measuring phagocytosis of Staphylococcus aureus by human neutrophils (polymorphonuclear leukocytes [PMNs]) is described. This assay utilizes 100 microliters of EDTA-anticoagulated whole blood and a simplified method of fluorescently labeling bacteria. A commercially available whole-blood lysing reagent allows for the removal of erythrocytes and the exclusion of external free or adherent bacteria. Phagocytized bacteria are unaffected by this reagent, so PMNs containing internalized bacteria can be easily identified by FCM. Advantages of this method include the following: (i) small sample size, (ii) no requirement for PMN separation, (iii) rapid reliable method of labeling the bacteria, (iv) ability to distinguish between adherent bacteria and those which are actually internalized, (v) avoidance of vital dyes as quenching agents, and (vi) ability to fix cells and store for future FCM analysis. PMID- 1500515 TI - Excretory-secretory antigenic components of Paragonimus heterotremus recognized by infected human sera. AB - Antigenic components of Paragonimus heterotremus metabolic products were revealed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) and immunoblot analysis of sera from patients with P. heterotremus infection, from patients with other illnesses, and from healthy adults. By SDS-PAGE, it was found that the metabolic products comprised more than eight major polypeptides. Immunoblot analysis revealed 11 components which were strongly recognized by paragonimiasis antisera. These antigenic components had molecular masses ranging from less than 12.3 kDa to 144 kDa. One antigenic band of 31.5 kDa was found to give a consistent reaction with paragonimiasis antisera (97% sensitivity). Of the other patient sera, only sera from patients with Fasciola sp. infection reacted with antigenic bands of 56, 38, and 18.5 kDa. The present findings suggest that the 31.5-kDa component is sensitive and specific for the diagnosis of human P. heterotremus paragonimiasis. PMID- 1500516 TI - Detection of genes in feces by booster polymerase chain reaction. AB - A 321-bp fragment intragenic to the gene ereA carried by Escherichia coli BM2195 was used as a model target to study the conditions under which DNA amplification by booster polymerase chain reaction can be used to detect specific bacterial DNA sequences in fecal specimens. When target E. coli cells were mixed with 41 freshly obtained fecal specimens, the polymerase chain reaction detection limit varied from 4.5 to 7.1 log CFU/g of feces, depending on the individual fecal specimen used to prepare the test sample. These variations were not statistically related to the sex or age of the subject from whom the specimen was obtained. After storage of the samples for 4 weeks at room temperature on swabs or filter papers, no loss in sensitivity was observed. PMID- 1500517 TI - Detection of Babesia microti by polymerase chain reaction. AB - Human babesiosis, which is caused by infection with the intraerythrocytic malarialike protozoan Babesia microti, has recently been diagnosed with increasing frequency in residents of New England. Diagnosis is difficult because of the small size of the parasite and the sparse parasitemia that is characteristic of most infections with this pathogen. We generated B. microti specific DNA sequence information by universal primer amplification of a portion of the eukaryotic 16S-like gene; this was followed by direct DNA sequence analysis. Specific primers were synthesized on the basis of this sequence information for use in the polymerase chain reaction (PCR). The PCR-based system demonstrates a strong bias for detection of B. microti as opposed to Babesia gibsoni and does not amplify vertebrate DNA. The analytical sensitivity of the system is approximately three merozoites. Blood specimens from 12 patients with clinically diagnosed and parasitologically confirmed babesiosis from Nantucket Island, Mass., were PCR positive in a blinded test of this procedure. Thus, DNA amplification may provide an adjunct to conventional methods for the diagnosis of human babesiosis and may provide a new means of monitoring therapy or enhancing epidemiological surveillance for this emerging pathogen. PMID- 1500518 TI - Isolation and characterization of a newly identified Haemophilus species from cats: "Haemophilus felis". AB - A gram-negative coccobacillus was isolated from the lower respiratory tract of a cat with chronic obstructive pulmonary disease. The isolate required CO2 and V factor for growth and was initially identified as Haemophilus paraphrophilus on the basis of its nutritional requirements, colony morphology, and some biochemical tests. Because of the host specificity of Haemophilus species and discrepancies in catalase, oxidase, and hemolytic activities, additional testing was done. Extensive biochemical testing, G+C content, and DNA reassociation studies indicated that the organism was distinct from other Haemophilus species. Therefore, the organism was identified as a previously unrecognized Haemophilus species and was tentatively named "Haemophilus felis." Bacteria identical to the original isolate were isolated from the nasopharynxes of 6 of 28 apparently normal cats, indicating that H. felis or H. felis-like organisms may be common members of the feline upper respiratory tract flora. PMID- 1500519 TI - Beta-glucuronidase activities of fecal isolates from healthy swine. AB - Research has shown that various percentages of fecal Escherichia coli isolates obtained from healthy subjects may be beta-glucuronidase negative. The ability to detect beta-glucuronidase activity among fecal E. coli isolates from healthy subjects may be affected by assay conditions. A study was conducted in which agar and broth media containing 4-methylumbelliferyl-beta-D-glucuronide (MUG) were used to examine beta-glucuronidase activities of fecal isolates from healthy swine. Rectal swabs were plated on MacConkey agar plus 100 mg of MUG per liter (MAC-MUG) and incubated at 35 degrees C for 24 h. Each of 986 isolates picked from MAC-MUG was inoculated into duplicate tubes of lauryl tryptose broth plus 50 mg of MUG per liter (LT-MUG). One set of tubes was incubated at 35 degrees C and the other set of tubes was incubated at 44.5 degrees C. Gas production and hydrolysis of MUG, indicated by fluorescence when observed with UV light with a wavelength of 360 nm, were determined after incubation for 24 and 48 h. A higher percentage (P less than 0.01) of isolates was MUG positive at 44.5 degrees C than at 35 degrees C after 24 h of incubation in LT-MUG. A higher percentage (P less than 0.01) of isolates was MUG positive after 48 h than after 24 h of incubation at both 35 and 44.5 degrees C. A lower percentage of isolates (P less than 0.05) was observed to be MUG positive on MAC-MUG agar compared with their MUG reactions in LT-MUG at 35 and 44.5 degrees C. Approximately 89% of the isolates identified were beta-glucuronidase-positive E. coli. The largest proportion of MUG-positive E. coli was detected with LT-MUG at 35 degrees C after 48 h of incubation. PMID- 1500520 TI - Use of polymerase chain reaction for detection of toxigenic Vibrio cholerae O1 strains from the Latin American cholera epidemic. AB - In January 1991, an outbreak of cholera started in Peru and spread throughout most of Latin America within 8 months. As of March 1992, over 450,000 cases and approximately 4,000 deaths have been reported to the Pan American Health Organization. The causative organism is toxigenic Vibrio cholerae O1 of the El Tor biotype and is distinct from the U.S. Gulf Coast strains. A polymerase chain reaction (PCR) that amplifies a 564-bp fragment of the cholera toxin A subunit gene (ctxA) was used to identify toxigenic V. cholerae O1 strains. A total of 150 V. cholerae O1 isolates were tested. They were of unknown toxin status, were associated with recent outbreaks, and were isolated from patients, food, and water. One hundred forty isolates were found to be toxigenic both by PCR and the routine diagnostic enzyme-linked immunosorbent assay. Thirty-eight known toxigenic strains isolated worldwide from 1921 to 1991 were also positive in the PCR. A collection of 18 nontoxigenic V. cholerae O1 strains, 35 Escherichia coli heat-labile-enterotoxin-I-producing strains, 26 Campylobacter strains, and 8 strains of Aeromonas hydrophila, previously reported to produce cholera toxin like toxin, were all negative in the ctxA PCR. We conclude that this PCR is a diagnostic method that specifically detects toxin genes in V. cholerae O1 strains in a reference laboratory. It is more rapid and less cumbersome than other diagnostic methods for detection of toxicity in these strains. PMID- 1500521 TI - Development and clinical evaluation of a polymerase chain reaction test for detection of Chlamydia trachomatis. AB - A polymerase chain reaction (PCR) for the detection of Chlamydia trachomatis was developed and evaluated. Two primer-probe sets were designed; one detected a specific sequence of the plasmid, and the other detected the gene encoding the major outer membrane protein. Both sets reacted species specifically and amplified sequences from all human serovars. A simple protocol was used for sample pretreatment. The PCR was optimized by addition of tetramethylammonium chloride and bovine serum albumin. The results of the PCR with the plasmid primer probe set were compared with those of culture and the Chlamydiazyme and Gen-Probe PACE 2 tests for urogenital specimens from 220 patients. The rates of prevalence of infection with C. trachomatis were 22.7, 16.4, 15.0, and 14.5%, respectively. The sensitivities of the Chlamydiazyme and Gen-Probe PACE 2 assays compared with culture were 66.7 and 61.1%, respectively, and their sensitivities compared with PCR were 60.0 and 60.0%, respectively. The sensitivity of culture compared with PCR was 70.0%. Forty-eight of the 50 specimens positive by PCR with the plasmid primer-probe set could be confirmed by PCR with the major outer membrane protein primer-probe set or culture. It is concluded that the PCR is the most sensitive technique for laboratory detection of C. trachomatis. PMID- 1500522 TI - Comparison of three methods for detection of group A streptococci in throat swabs. AB - Group A streptococci are generally detected in throat swabs by (i) rapid antigen tests, (ii) conventional culture, or (iii) combinations of both. Direct fluorescent-antibody testing of a 2-h enrichment broth (FA/EN) was an accepted method for same-day results before the advent of rapid antigen tests. We compared FA/EN in Todd-Hewitt Broth (THB) with conventional culture and a rapid antigen test, TestPack Strep A (TPS). Nine hundred seventy specimens were evaluated in this study. Cultures were performed for 48 h on sheep blood agar (SBA) incubated aerobically and on a selective agar for group A streptococci (SSA) incubated in 5 to 10% CO2. Following a 2-h incubation, the fluorescent-antibody test was performed. A subculture of the centrifuged sediment from the THB enrichment was also done. In comparison with a positive culture on SBA or SSA or subculture of the THB pellet, the sensitivities and specificities of the different methods were as follows: SBA, 92 and 100%; SSA, 92 and 100%; TPS, 68 and 99%; FA/EN, 88 and 98%. The FA/EN method offers the potential for definitive finalized reports on the same day as specimen collection with greater sensitivity than TPS. This study included sequential plating and rapid antigen testing of a single swab. In a separate set of experiments to validate this study design, it was shown that recovery of streptococci from swabs plated sequentially on five plates did not vary with the order of plating and the actual proportion of organisms recovered from a swab on a single plate was only 1%. PMID- 1500523 TI - Comparison of a neutralization enzyme immunoassay and an enzyme-linked immunosorbent assay for evaluation of immune status of children vaccinated for mumps. AB - A 50% neutralization enzyme immunoassay (N50-EIA) was compared with an indirect enzyme-linked immunosorbent assay (ELISA) for determining mumps virus antibodies in three consecutive serum samples from 138 children vaccinated with a live mumps vaccine at the age (in years) of 1.5. By the N50-EIA, most (132 of 138) preserum samples did not show neutralizing activity. Eight to 12 weeks after vaccination, 17 of the children were still negative, but only 7 remained so after 2.5 years, resulting in a seroconversion rate of 125 of 132 (95%). Over the same period, the neutralization geometric mean titer rose from 3.6 to 9.9. By an indirect ELISA, 128 of 138 preserum samples were found negative. The early and late postvaccination sera of 8 children were ELISA negative, resulting in a seroconversion rate of 120 of 128 (94%). Only two children remained seronegative by both methods. Seven of the late postvaccination serum samples yielded noncorresponding results, reflecting 95% correlation between both methods. Due to cross-reactivity with parainfluenza viruses, the ELISA proved to be less specific, but on the other hand, it showed a greater sensitivity than the N50 EIA. PMID- 1500524 TI - Evaluation of the E test by using selected gram-positive bacteria. AB - The E test (AB Biodisk NA Inc.) was compared with standard reference methods using the National Committee for Clinical Laboratory Standards's recommendations for determining the MICs of four selected antibiotics against 208 clinical isolates of gram-positive bacteria. These bacteria included 32 strains of Streptococcus pneumoniae, 25 strains of Enterococcus faecium, 20 strains of oxacillin-sensitive Staphylococcus aureus (OSSA), 96 strains of oxacillin resistant S. aureus (ORSA), and 35 strains of coagulase-negative staphylococci. Evaluation included MIC accuracy within 1 dilution, reproducibility testing, and cost analysis. There was 94% agreement between the E test and the reference method in testing S. pneumoniae and penicillin G. There was 92% agreement with ampicillin and 100% agreement with vancomycin in testing E. faecium isolates. Accuracy of the oxacillin E test with staphylococci was significantly improved by the use of salt-supplemented Mueller-Hinton agar, for an agreement of 100% with coagulase-negative staphylococci and oxacillin-sensitive S. aureus and that of 85% with oxacillin-resistant S. aureus, with no major discrepancies. The E test with American Type Culture Collection isolates and clinical strains gave excellent reproducibility and was less costly than microdilution panels when used to test fewer than three antibiotics. The E test is a simple, reliable, reproducible, and cost-effective method for MIC determination for gram-positive organisms. PMID- 1500525 TI - Enterohemorrhagic Escherichia coli associated with hemolytic-uremic syndrome in Chilean children. AB - A clinicoepidemiological study was undertaken to determine if enterohemorrhagic Escherichia coli (EHEC) was associated with hemolytic-uremic syndrome (HUS) in children in Santiago, Valdivia, and Temuco, Chile. Prospective surveillance detected 20 hospitalized cases of HUS in children less than 4 years of age in these cities from March 1988 to March 1989. Each HUS patient was matched (by sex and age) with two control children (hospitalized elective-surgery patients). To detect EHEC, DNA from stool culture isolates of E. coli was detected by hybridization with biotin-labelled DNA probes specific for the EHEC virulence plasmid, Shiga-like toxin I (SLT-I) or SLT-II. Stool cultures from 6 of 20 cases (30%) and from 2 of 38 controls (5.3%) yielded EHEC (P = 0.0158). EHEC isolates from all HUS cases hybridized with the EHEC plasmid probe and with probes for SLT I or -II (or both). The serogroups of the isolates included O157, O26, and O111. EHEC causes HUS in Chile, and the biotinylated gene probes are practical diagnostic tools for epidemiologic studies. PMID- 1500526 TI - Retrospective evaluation of two latex agglutination tests for detection of circulating antigens during invasive candidosis. AB - Two latex agglutination tests for the detection of Candida antigens, Pastorex Candida (Sanofi Diagnostics Pasteur, Marnes-la-Coquette, France) and Cand-Tec (Ramco Laboratories, Inc., Houston, Tex.), were applied to 79 serum samples from 19 patients who were retrospectively selected on the basis of mycological and clinical evidence of C. albicans infection and the availability of serial serum samples taken near the date of a positive culture. The specificity in 60 control individuals was 100% for Pastorex and 98.3% for Cand-Tec. The tests scored positive for 10 (52.6%) and 9 (47.4%) patients, respectively. Pastorex detected antigen in only 3 of 12 patients (25%) with positive antibody detection tests, but was positive for all 7 patients (100%) who produced no or a low antibody response, suggesting that the test performs better in the absence of antibodies. However, the sensitivity of Pastorex also increased with the number of samples available per patient, which was lower for high-antibody-responder patients (2.8 versus 5.7). If the patients who provided only one or two serum samples were eliminated, the sensitivity of Pastorex rose to 76.9%. For the Cand-Tec, the sensitivity was not related to the presence of antibodies, nor was it related to the number of samples per patient. The observed antigenemia was transient with both Pastorex and Cand-Tec. Only 12.5% of the positive reactions occurred on the same serum sample, confirming that the two tests react with different antigens. A positive antigen test preceded other diagnostic indications for 6 of 10 Pastorex positive patients and 5 of 9 Cand-Tec-positive patients. PMID- 1500527 TI - Presence of specific immunoglobulin A-secreting cells in peripheral blood after natural infection with Shigella sonnei. AB - The appearance of antigen-specific immunoglobulin A (IgA) antibody-secreting cells (ASCs) following natural infection with Shigella sonnei during a common source outbreak caused by this organism was evaluated in a modified enzyme-linked immunosorbent assay (ELISPOT). A mean IgA ASC value of 2,131.6/10(6) cells against homologous S. sonnei lipopolysaccharide (LPS) was detected in blood samples obtained from patients with bacteriologically proven S. sonnei shigellosis 5 and 10 days after the onset of disease. In the same blood samples, the level of ASC measured against heterologous antigen (Shigella flexneri serotype 2a LPS) was significantly lower than that of the homologous antigen (mean value, 33.12/10(6) cells). Furthermore, the mean number of activated B cells that secreted anti-S. sonnei LPS antibodies was significantly higher among patients with S. sonnei shigellosis than it was among patients with non-Shigella diarrhea (2.5/10(6) cells; standard error, 1.0) and healthy subjects (5.1/10(6) cells; standard error, 2.3) (P less than 0.05). The anti-LPS IgA ASC activity was easily detected within 5 days of the onset of disease, a point at which the levels of anti-S. sonnei LPS IgG and even IgA antibodies were hardly detectable in serum. PMID- 1500528 TI - DNA fingerprinting of Escherichia coli O157:H7 strains by pulsed-field gel electrophoresis. AB - Pulsed-field gel electrophoresis of genomic DNA was carried out on Escherichia coli O157:H7 strains from different geographic locations to determine its value in an epidemiological survey of O157 infections. Pulsed-field gel electrophoresis of XbaI-digested DNA fragments clearly separated E. coli O157:H7 strains from nontoxigenic E. coli O157:H19, O157:H43, and O157:H45 strains and from Shiga-like toxin-producing E. coli strains of other serogroups. However, among the E. coli O157:H7 strains, the restriction patterns either were identical or differed only by a few fragment bands. In some cases, it was therefore impossible to distinguish among epidemiologically unrelated strains. Hybridization experiments with a DNA probe complementary to Shiga-like toxin II sequences revealed that the Shiga-like toxin II genes were located on DNA fragments of different lengths. Our data show that for a single highly conserved clone, such as E. coli O157:H7, other typing techniques may need to be performed in addition to DNA fingerprinting in epidemiological surveys. PMID- 1500529 TI - Characterization of a DNA probe for detection of Mycobacterium tuberculosis complex in clinical samples by polymerase chain reaction. AB - We cloned and sequenced a DNA fragment from Mycobacterium tuberculosis for use in the identification of members of the M. tuberculosis complex. The DNA probe for culture confirmation had a sensitivity and a specificity of 100%. By using primers developed from this probe, the polymerase chain reaction detected 20 mycobacteria by ethidium bromide staining. This polymerase chain reaction system demonstrated 98% sensitivity and 100% specificity for detection of the M. tuberculosis complex in 200 sputum specimens. PMID- 1500530 TI - Evaluation of a urease-based confirmatory enzyme-linked immunosorbent assay for diagnosis of Neisseria gonorrhoeae. AB - A new urease-based enzyme-linked immunosorbent assay utilizing novel monoclonal antibodies was evaluated for the culture confirmation of Neisseria gonorrhoeae, with 270 isolates of N. gonorrhoeae, 56 isolates of diverse Neisseria spp., and 29 Moraxella isolates. The test was highly specific (100.00%) and sensitive (97.83%). No cross-reactions were observed with any of the Neisseria or Moraxella isolates tested. Fifty percent (3 of 6) of the false-negative results were obtained with isolates of serovar IA-4, a serovar rarely encountered in North America. PMID- 1500531 TI - Evaluation of two colored latex kits, the Wellcolex Colour Salmonella Test and the Wellcolex Colour Shigella Test, for serological grouping of Salmonella and Shigella species. AB - Two colored latex kits (the Wellcolex Colour Salmonella Test [WCT-Salmonella] and the Wellcolex Colour Shigella Test [WCT-Shigella]; Division Diagnostics, Laboratories Wellcome S.A., Paris, France), which allow identification of the most frequently encountered Salmonella serogroups and Shigella species, respectively, were evaluated. WCT-Salmonella and WCT-Shigella yielded sensitivities of 98.4 and 98%, respectively, and a specificity of 100% when they were tested on pure cultures received at a reference laboratory. PMID- 1500532 TI - Further consideration of the clonal nature of Salmonella typhi: evaluation of molecular and clinical characteristics of strains from Indonesia and Peru. AB - We examined envelope protein profiles, chromosomal restriction endonuclease digest patterns, and immune responses to envelope proteins for collections of Salmonella typhi strains isolated in Peru and Indonesia. Only minor differences in envelope protein patterns were apparent among strains. Strains from 7 of 20 Indonesian patients had a distinct chromosomal digest pattern compared with patterns of Peruvian and other Indonesian strains. Strains with this pattern carried the gene for the j flagellar antigen (H1-j); differences in response to envelope proteins of j and d strains were noted on immunoblot analysis. Our data suggest that there are genotypic and phenotypic differences among S. typhi strains. The clinical importance of these differences remains to be fully evaluated; however, in this study it was not possible to show a clear correlation between strain characteristics and disease severity. PMID- 1500533 TI - Proposed interpretive criteria and quality control parameters for testing susceptibility of Neisseria gonorrhoeae to beta-lactam-clavulanate combinations. AB - To support future clinical studies, in vitro susceptibility tests were examined to determine whether Neisseria gonorrhoeae could be tested reliably against two beta-lactam-clavulanate combinations. All isolates that were tested appeared to be susceptible to amoxicillin and ticarcillin in combination with clavulanic acid. In the absence of resistant isolates, only a breakpoint for a susceptible category could be defined for agar dilution tests with amoxicillin-clavulanic acid (MIC of less than or equal to 2.0/1.0 micrograms/ml is tentatively proposed). For disk diffusion tests, a corresponding breakpoint zone diameter of greater than or equal to 28 mm is suggested. The validity of the breakpoints for penicillinase-negative penicillin-resistant strains awaits clinical data. Proposed quality control limits for testing amoxicillin-clavulanic acid by agar dilution and disk diffusion methods are a MIC of 0.25/0.125 to 1.0/0.5 micrograms/ml and zones of 30 to 40 mm in diameter for N. gonorrhoeae ATCC 49226, a MIC of 0.125/0.06 to 0.5/0.25 micrograms/ml for Staphylococcus aureus ATCC 29213, and zones of 30 to 38 mm for S. aureus ATCC 25923. Ticarcillin-clavulanate is currently tested against other species by preparing doubling dilutions of ticarcillin with a constant 2 micrograms of clavulanate per ml. By that method, all gonococci were susceptible to low concentrations. However, the amount of clavulanic acid that is included (2 micrograms/ml) will, by itself, inhibit many strains of N. gonorrhoeae. Consequently, the role of ticarcillin in the combination cannot be determined, and such tests are not recommended. PMID- 1500534 TI - Primary isolation of human T-cell leukemia-lymphoma virus types I and II: use for confirming infection in seroindeterminate blood donors. AB - We describe the use of an immunofluorescence assay and coculture to confirm human T-cell leukemia-lymphoma virus (HTLV) infection. Peripheral blood mononuclear cells from 32 of 32 seropositive donors were positive in the immunofluorescence assay, and 63% of their cocultures produced p24 antigen. Specific antibodies distinguished HTLV type I (HTLV-I) from HTLV-II. HTLV-I or HTLV-II was isolated from donors with indeterminate serologic test results. PMID- 1500536 TI - Comparison of the MEASLESTAT M test kit with the sucrose density gradient centrifugation-hemagglutination inhibition method for detection of measles virus specific immunoglobulin M. AB - A new commercial kit, MEASLESTAT M (Whittaker Bioproducts, Inc.), was compared with the sucrose density gradient centrifugation-hemagglutination inhibition method for the detection of measles virus-specific immunoglobulin M. Overall agreement between the two procedures was 97.1% for 104 single and paired serum samples tested. The sensitivity and specificity of MEASLESTAT M were 98.4 and 95.2%, respectively. PMID- 1500535 TI - In vitro antibody secretion by peripheral blood mononuclear cells as an expression of the immune response to Brucella spp. in humans. AB - We developed an assay to detect antibodies spontaneously secreted in vitro by peripheral blood mononuclear cells (PBMC) against Brucella spp. High levels of anti-Brucella immunoglobulin G (IgG) and/or IgM and/or IgA antibodies were detected in the cell supernatant solution of PBMC cultures for 12 patients suffering from acute or focalized brucellosis and for 5 patients recently vaccinated against brucellosis. This spontaneous in vitro antibody production disappeared 5 to 20 months after onset of clinical signs and 20 to 27 days after vaccination. The transient character of this anti-Brucella antibody production by PBMC is consistent with a temporary in vivo stimulation of the immune system by Brucella antigens. Detection of this secretion could improve the diagnosis of evolutive brucellosis. PMID- 1500537 TI - Identification of Ehrlichia chaffeensis morulae in cerebrospinal fluid mononuclear cells. AB - We report a case of ehrlichiosis in a 72-year-old man who developed extreme lethargy, acute renal failure requiring hemodialysis, and respiratory insufficiency requiring intubation. Lumbar puncture performed on the second day of hospitalization revealed significant cellular pleocytosis. Ehrlichia morulae were tentatively identified in mononuclear cells in routinely processed Wright stained cytospin preparations of cerebrospinal fluid (CSF). Identification was confirmed by a specific immunocytochemical staining procedure. Subsequent identification specifically as Ehrlichia chaffeensis morulae was established by polymerase chain reaction analysis, which revealed E. chaffeensis-specific DNA in CSF, bone marrow, and blood samples; by indirect fluorescent-antibody analysis, the patient developed an antibody titer of 32,768 against E. chaffeensis antigen. The patient responded to intravenous therapy with doxycycline and dexamethasone. Subsequently, neurologic, hematologic, renal, and pulmonary status had returned to baseline at follow-up 12 weeks after admission. To our knowledge, this is the first identification of E. chaffeensis morulae in CSF cells in an infected patient. PMID- 1500538 TI - Clamped homogeneous electric field gel electrophoresis typing of Torulopsis glabrata isolates causing nosocomial infections. AB - Thirty isolates of Torulopsis glabrata were examined by pulsed-field gel electrophoresis, which resolved 13 DNA pieces, allowing the identification of 12 types. Bands at 1,400, 1,200, 1,070, 1,025, 681, and 500 kbp were conserved. When applied to 18 isolates from an outbreak, 10 distinct types were identified by this technique. Seven patients had isolates which were identical. PMID- 1500539 TI - CLEARVIEW Chlamydia test for detection of chlamydiae in cervical specimens. PMID- 1500540 TI - Significant infection caused by Staphylococcus warneri. PMID- 1500541 TI - Ontogenesis of the pyramidal cell of the mammalian neocortex and developmental cytoarchitectonics: a unifying theory. AB - The prenatal development of the mammalian neocortex has been analyzed, with the rapid Golgi method, in a variety of experimental animals (hamster, mouse, rat, and cat) and in humans. A new developmental conception of the structural organization of the mammalian neocortex is discussed. Neocortical development begins with the establishment of the primordial plexiform layer (PPL) which precedes and is a prerequisite for the subsequent formation of the cortical plate (CP). The formation of the CP occurs, in its entirety, within the PPL. During its development, three fundamental neuronal events occur: migration, early differentiation, and late maturation. All migrating neurons, travelling on radial glial fibers, reach layer I, develop an apical dendrite, and establish contacts with its elements. These newly differentiated neurons assume similar morphology resembling embryonic pyramidal cells. As such, an early differentiation stage common to all neurons of the CP is established. During the late maturation stage, all CP neurons acquire their specific phenotypic structural and functional features. Only pyramidal neurons retain and expand their original connections with layer I while other neuronal types lose these connections. The pyramidal cell is redefined in developmental terms: the neocortex's pyramidal cell is both structurally and functionally locked into position between layer I and the cortical depth of its soma. During mammalian evolution pyramidal cells are forced to structurally and functionally elongate their apical dendrite outwardly to accommodate an increasing amount of information without losing either their original anchorage to layer I or their cortical depth. This unique property of pyramidal neurons is considered to be a mammalian innovation. Based on these observations, a unifying developmental cytoarchitectonic theory applicable to all mammals is proposed. The theory considers the CP to be a mammalian innovation and to represent a single, stratified, and expanding telencephalic nucleus. The theory envisions the mammalian neocortex as an open biological system capable of progressive expansion by the recruitment and transformation of primitive neurons from upper layer II into pyramidal cells. Hence, the number of pyramidal cell strata increases over the course of mammalian phylogeny. The developmental roles of layer I in the migration of neurons, formation of the CP, unique morphology of pyramidal cells, and overall structural organization of the mammalian neocortex are emphasized. PMID- 1500542 TI - Heterogeneity of layer II neurons in human entorhinal cortex. AB - Abnormalities in the layer II neurons of human entorhinal cortex have been implicated in the pathophysiology of Alzheimer's disease and schizophrenia. The reported abnormalities are not homogeneously distributed throughout the entorhinal cortex, suggesting that layer II of entorhinal cortex may contain different subpopulations of neurons, each with a different susceptibility to pathological mechanisms. In order to investigate the possible heterogeneity of neurons in layer II of human entorhinal cortex, we first identified distinct subdivisions of human entorhinal cortex by adapting the cytoarchitectonic criteria for subdivisions of monkey entorhinal cortex described by Amaral et al. (J Comp Neurol 264:326, 1987). The morphology and regional distribution of distinct subpopulations of human layer II neurons were determined through the use of immunohistochemical techniques. Multipolar, stellate, and modified pyramidal neurons in the characteristic cell clusters or islands of layer II were immunoreactive for nonphosphorylated neurofilament proteins. The intensity of immunoreactivity for the nonphosphorylated neurofilament proteins gradually increased along the rostrocaudal axis of entorhinal cortex and was primarily due to a similar gradient in the density of labeled neurons per island. The calcium binding protein calbindin D-28K was found in both pyramidal and nonpyramidal neurons in layers II and superficial III. The distribution of calbindin immunoreactive neurons also depended upon the region of entorhinal cortex. In rostral entorhinal cortex, labeled neurons were scattered throughout the superficial layers, whereas in caudal entorhinal cortex, distinctive patches of small calbindin-immunoreactive neurons were found among the layer II islands. Another calcium-binding protein, parvalbumin, was present in nonpyramidal neurons in layers II and III that were distinct from those containing calbindin. The regional distribution of parvalbumin-positive neurons was very similar to that of the neurofilament immunoreactive neurons; in rostral entorhinal cortex very few parvalbumin-labeled neurons were present but their frequency gradually increased in the caudal direction. In addition, punctate parvalbumin immunoreactivity was frequently encountered in the location of the nonphosphorylated neurofilament protein-positive layer II islands. These findings demonstrate that layer II of human entorhinal cortex contains distinct subpopulations of neurons, that the relative density of each subpopulation differs across cytoarchitectonic regions, and that the patterns of distribution of these subpopulations are in some cases similar and in other cases complementary. This heterogeneity in the organization of layer II of human entorhinal cortex has important implications for the study of some neuropsychiatric disorders. PMID- 1500543 TI - Two classes of vesicles are present and change in relative proportion during post embryonic development of rectifying electrical synapses in the crayfish. AB - The size and shape of vesicles at junctional appositions of the rectifying electrical synapses between the medial giant fibre and motor giant neurone of the crayfish were measured during the first 2 months after hatching. Summed data over this period reveal a bimodal distribution in vesicle diameter. From the day of hatching until about 7 days of age, small vesicles (circa 25 nm diameter) predominate. From day 7 onwards, larger vesicles (circa 55 nm diameter) occur in increasing numbers, until at day 56 they constitute about 85% of the population at any one junctional apposition. At intermediate ages (day 7-28) individual junctional appositions may show the same bimodal distribution in size as does the age group as a whole, indicating that large and small vesicles occur together at the same junction. The larger vesicles are mainly circular, while the small vesicles are pleomorphic, with shapes ranging from almost circular down to a shape factor of about 0.6. PMID- 1500544 TI - Connections from the lateral vestibular nucleus to the upper cervical spinal cord of the cat: a study with the anterograde tracer PHA-L. AB - The projections of neurons in the lateral vestibular nucleus (LVN) to the upper cervical spinal cord of the cat were investigated by means of the anterograde tracer Phaseolus vulgaris leucoagglutinin (PHA-L). At the junction of C1 and C2, axons were distributed bilaterally in the ventromedial funiculi, and ipsilaterally in the ventrolateral and lateral funiculi. The majority of boutons were found ipsilateral to the injection sites and most of these boutons were found at the base of the ventral horn and throughout the medial two-thirds of lamina VIII. A more modest termination zone was found along the ventral border of lamina VII and a small number of boutons were scattered in the dorsal horn. Contralateral termination zones were similar to the ipsilateral projections. There were significant changes in the distribution of vestibulospinal axons and density of boutons at the junction of C3 and C4. At this level, most vestibulospinal axons travelled ipsilaterally and were found along the medial border of the ventromedial funiculus and the ventral margin of the ventrolateral funiculus. The overall distribution of boutons near the border of C3 and C4 was similar to the pattern seen at the junction of C1 and C2. However, bouton density fell by a factor of three. Large zones of the grey matter were devoid of boutons in individual experiments. These results demonstrate that the projections of neurons in the LVN to the upper cervical spinal cord are densest in the regions containing motoneurons supplying suboccipital muscles. This result suggests that monosynaptic connections to those motoneurons may be an important part of the neural circuitry responsible for vestibulocollic reflexes. However, the large number of boutons found in regions dorsal to motoneuron nuclei in all upper cervical segments indicates that the primary path from vestibulospinal axons to neck motoneurons may be indirect and involve relays via spinal interneurons. PMID- 1500545 TI - Proteolytic activity of proteinases on macropeptide isolated from kappa-casein. AB - Proteolytic activities of chymosin, bovine pepsin, Mucor miehei rennet, Cryphonectria parasitica (formerly Endothia parasitica) rennet, trypsin, and chymotrypsin on kappa-casein macropeptide were measured. Macropeptide solutions (10 mg/ml of .05 M, pH 6.6 phosphate buffer) were incubated with the enzymes at 37 degrees C for various times, and their reactions were stopped by adding .025 ml of pepstatin (1 mg/ml of methanol). Peptides released from kappa-casein macropeptide were then fractionated using reverse-phase HPLC. At the pH of milk (pH 6.6), kappa-casein macropeptide was resistant to enzymic action by chymosin, bovine pepsin, and M. miehei and C. parasitica rennets. Bovine pepsin hydrolyzed kappa-casein macropeptide at pH 3. kappa-Casein macropeptide was readily hydrolyzed at pH 6.6 by trypsin and chymotrypsin. Possible physiological functions of the kappa-casein macropeptide are discussed in light of these findings. PMID- 1500546 TI - Klebsiella pneumoniae as a spoilage organism in mozzarella cheese. AB - A high concentration of total and fecal coliforms (5 x 10(8) and 3 x 10(7) cfu/g, respectively) was observed in samples representative of two production lots of Mozzarella cheese from a local dairy. Contamination was manifested by the swelling of plastic pouches and the formation of gas holes in Mozzarella cheese. Aerobic and anaerobic sporeformers, heterofermentative lactic acid bacteria, propionibacteria, and yeasts were absent. Of the 41 isolates identified, there were 37 Klebsiella pneumoniae, 2 Klebsiella oxytoca, 1 Enterobacter aerogenes, and 1 Escherichia coli. Exposure at 63 degrees C for 15 min caused the death of all total and fecal coliforms. PMID- 1500547 TI - Survival of Lactobacillus acidophilus and Bifidobacterium bifidum in ice cream for use as a probiotic food. AB - Probiotic ice cream was made by fermenting a standard ice cream mix with Lactobacillus acidophilus and Bifidobacterium bifidum cultures and then freezing the mix in a batch freezer. Survival of the L. acidophilus and B. bifidum, as well as beta-galactosidase activity, was monitored during 17 wk of frozen storage at -29 degrees C. After freezing of the fermented mix, bacterial counts were 1.5 x 10(8) cfu/ml for L. acidophilus and 2.5 x 10(8) cfu/ml for B. bifidum. Seventeen weeks after freezing, these counts had decreased to 4 x 10(6) and 1 x 10(7) cfu/ml, respectively. During the same period, beta-galactosidase activity decreased from 1800 to 1300 units/ml. Probiotic ice cream was prepared at pH 5.0, 5.5, and 6.0 to determine consumer preferences and was compared with standard Utah State University "Aggie" ice cream. All samples were strawberry-flavored and were evaluated by 88 judges. The preferred pH of probiotic ice cream, based on overall acceptance, was pH 5.5. We demonstrated that probiotic ice cream is a suitable vehicle for delivering beneficial microorganisms such as L. acidophilus and B. bifidum to consumers. The bacteria can be grown to high numbers in ice cream mix and remain viable during frozen storage. PMID- 1500548 TI - Mammary-derived growth inhibitor protein and messenger ribonucleic acid concentrations in different physiological states of the gland. AB - Expression of mammary-derived growth inhibitor in tissue from lactating and involuting bovine mammary glands was investigated. Seventeen lactating, pregnant (220 to 272 d in gestation) cows were divided in two groups of 8 and 9 cows each. Cows of the first group were slaughtered while in lactation. Cows of the second group (9 involuting cows) were slaughtered at 13 to 52 d following sudden cessation of milking. High concentrations of mammary-derived growth inhibitor (.63% of the total protein) were detected in mammary tissue of lactating cows. Mammary-derived growth inhibitor (less than .10% of the total protein) was dramatically reduced during most of the involution period (13 to 45 d following cessation of milking). Mammary-derived growth inhibitor was again detected (.28% of the total protein) during the last stage of the involution (46 to 53 d after cessation of milking), which coincided with colostrum formation. When steady state concentrations of mammary-derived growth inhibitor mRNA were examined, the results obtained mirrored those obtained at the protein concentration. These data suggest that regulation of mammary-derived growth inhibitor occurs via modulation of the steady state concentration of its mRNA. Furthermore, there is a strong correlation between mammary-derived growth inhibitor expression and lactation in dairy cows. PMID- 1500549 TI - Diagnosis of Staphylococcus aureus intramammary infection by detection of specific antibody titer in milk. AB - The diagnostic value of the determination of Staphylococcus aureus antibody titer in milk as a method for identification of mammary quarters with S. aureus IMI was evaluated. Ten cows with a history of S. aureus IMI and 9 cows with no history of S. aureus IMI were sampled daily for 10 d. Quarter and composite milk samples were collected and processed by standard methods for concentration of S. aureus, S. aureus antibody titer (percentage of positive laboratory control), and SCC (cells per milliliter). Microbiologic culture identified 13 S. aureus-infected quarters from the 10 cows with a history of S. aureus IMI. Only 2 of the 130 samples (1.5%) from these infected quarters had undetectable concentrations of S. aureus. Antibody titers in milk from infected quarters of infected cows were below the previously established level considered to be indicative of IMI in 6 of 130 samples (4.6%). Four samples from infected quarters of infected cows had titers considered to be in the suspect range. The sensitivity of the antibody test was 83% (13% SE) when the suspect samples were included and 86% (12% SE) when they were not. Milk from uninfected quarters of cows with S. aureus IMI tended to have S. aureus antibody titers greater than the test's positive control, which would suggest that the quarters were infected with S. aureus. Antibody titer was below the infection threshold level in all pooled samples of uninfected cows, suggesting that the test correctly identified all cows free of S. aureus IMI.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1500550 TI - Coculture of in vitro fertilized bovine embryos with oviductal epithelial cells originating from different stages of the estrous cycle. AB - Bovine embryos derived from in vitro fertilization procedures were cocultured in vitro with oviductal cells obtained from heifers between d 4 and 6 or d 14 and 16 of the estrous cycle. In addition, proteins secreted by oviductal cells isolated between d 4 and 6 or d 14 and 16 of the cycle were monitored. Embryos (2- to 4 cell) were incubated in Tissue Culture Medium-199 with 10% fetal bovine serum with or without oviductal cells at 39 degrees C for 10 d following in vitro insemination. There were more morulae, blastocysts, and hatched blastocysts following coculture with oviductal cells than with culture in medium alone. However, no differences were noted in embryo development following coculture with oviductal cells obtained between d 4 and 6 or d 14 and 16 of the estrous cycle. Also, no differences were detected in the amount of [35S]methionine-labeled proteins secreted by oviductal cells isolated from different days of the estrous cycle. These results indicate that oviductal epithelial cells isolated from early and late luteal phases of the estrous cycle will effectively support early embryonic development following prolonged in vitro culture. PMID- 1500551 TI - Effect of progesterone on the expression of estrus at the first postpartum ovulation in dairy cattle. AB - Fifty-two lactating Holstein cows were randomly assigned to receive either a progesterone-releasing (2 g of progesterone) or a control-releasing intravaginal device (0 g of progesterone). Intravaginal devices were inserted on d 10 and removed on d 15 postpartum. Daily blood samples were collected from d 10 to 90 postpartum for subsequent determination of progesterone concentrations. Observations for estrus were conducted three times daily in a dirt paddock containing a testosterone-treated cow. Serum concentrations of progesterone in the progesterone-releasing intravaginal device group were elevated on d 11, 12, 13, 14, and 15 compared with those of the control group. The days to first post partum ovulation were similar between the treated and control groups, respectively (30.6 vs. 30.5 d). Also similar was the proportion of cows expressing estrus at first, second, and third postpartum ovulations (9/27 vs. 3/24, 14/23 vs. 15/21, and 14/21 vs. 9/15, respectively), length of the first postpartum estrous cycle (17.9 vs. 18.3 d), and peak serum concentrations of progesterone during the first estrous cycle (3.5 vs. 2.9 ng/ml). These data indicate that administration of progesterone early postpartum did not increase the proportion of cows expressing estrus at the first ovulation. PMID- 1500552 TI - Effect of recombinant bovine somatotropin on estradiol-induced estrous behavior in ovariectomized heifers. AB - To evaluate whether bST administration could affect the intensity of estrous behavior in the absence of the ovary, 17 ovariectomized heifers were assigned to receive a placebo or 500 mg/14 d of recombinant bST and were induced to display behavioral estrus by administration of 2 mg of estradiol cypionate. Estrous behavior was monitored for the following 60 h with a surveillance camera and a video recorder, and mounting activity was quantified. Blood samples were collected before and after bST administration. Administration of bST numerically elevated plasma insulin and NEFA and caused a significant increase in concentration of insulin-like growth factor-I in plasma. Heifers that received bST started to display estrous behavior later (24.5 +/- 1.1 and 21.9 +/- 1.1 h after estradiol administration for bST and placebo treatments, respectively), displayed estrous behavior of shorter duration (bST, 13.2 +/- 1.2 vs. placebo, 15.8 +/- 1.1 h), and instigated fewer mounting events (bST, 45.5 +/- 5.9 vs. placebo, 62.6 +/- 5.7 mounts) than control heifers, although only the number of mounting events was significantly different between the two groups. PMID- 1500553 TI - Water partitioning and intake prediction in dry and lactating Holstein cows. AB - Data from four energy and N balance trials with lactating Holstein cows (n = 329) and one trial with dry cows (n = 60) were used to predict free water intake and water-related traits. Lactating cows were between 36 and 159 DIM and, individually, were allowed ad libitum water and forage (corn silage without or with wilted haycrop silage) plus concentrates; dry cows accessed ad libitum water and single forages (grass, clover, or alfalfa, as hays or as wilted silages, or corn silage) varying in maturity. Intake of DM per day and dietary DM percentage were significant and positively related predictors of free water intake in dry and lactating cows. Daily milk yield (range 16 to 52 kg/d) was related linearly to water consumption (.60 L/kg of milk), and season effect in lactating cows was curvilinear; peak water intake was in late June and nadir in late December. Ration CP percentage (DM basis) affected free water intake only in dry cows; 1 unit of increase resulted in an increase of about 1 kg/d in water intake between 12 and 13% CP. As ration moisture dropped from 70 to 40%, free water intake increased about 7 L/d in dry cows, but this was accompanied by a drop of 15 L/d in total water intake (free plus feed water). Free water intakes were predicted with R2 of .64 and .69 in dry and lactating Holstein cows, respectively. Fecal water and urine outputs also were predicted. We found no significant relationship between DM content of the diet and the resulting ad libitum intake in either dry or lactating cows. PMID- 1500554 TI - Response of Holstein cows to corn gluten meal used to increase undegradable protein in early or later lactation. AB - Supplemental corn gluten meal was used to raise CP by 1.1 to 1.5 percentage units and undegradable intake protein from 35 to 39% of CP in the corn-based diet of parity 1 or greater Holstein cows to study effects of undegradability, parity, stage of lactation, and interactions on DMI, milk yield and composition, BW, and related traits during complete lactations. Cows were assigned at calving to treatments (n = 30, 8 primiparous): control, supplement wk 1 to 8 postpartum (early), or supplement wk 9 to 44 postpartum (late). Total lactation means were not affected significantly by treatments. Supplementation with undegradable protein enhanced forage and, thus, total DMI in later lactation by pluriparous cows; it apparently spared BW loss wk 1 to 8 postpartum and enhanced BW recovery thereafter in first lactation cows with no effect in older cows. Effects of supplementation on milk yield were small, and they were negative in early lactation and generally positive in late lactation; effects were positive on fat test in early lactation for both parity categories but distinctly negative for parity 1 cows in late lactation. Supplementation of undegradable protein in late lactation also decreased milk protein content in parity 1 cows and raised it in older cows. Data suggest that Lys may have been first-limiting, followed by Ile in early lactation and Met in late lactation, and that AA adequacy may be more important than undegradability in ration protein balancing. For most traits measured, treatment by parity interactions were significant, indicating that parity 1 cows did not respond in the same way as older ones to protein supplementation. PMID- 1500555 TI - Infusion of long-chain fatty acids varying in saturation and chain length into the abomasum of lactating dairy cows. AB - Free long-chain fatty acids were infused into the abomasum of lactating dairy cows to determine postruminal effects on feed intake, production and composition of milk, nutrient digestibilities, and metabolites in blood. Four Holstein cows averaging 120 DIM and fitted with ruminal cannulas were used in a 4 x 4 Latin square design with 14-d periods. Treatments were abomasal infusions of 1) control, 168 g/d of meat solubles (carrier for fatty acids), 2) control plus 450 g/d of mostly saturated fatty acids (C16:C18 = .75), 3) control plus 450 g/d of a mixture of saturated and unsaturated fatty acids (C16:C18 = .40), and 4) control plus 450 g/d of mostly unsaturated fatty acids (C16:C18 = .11). Production of milk and milk components, DMI, and intake of digestible energy decreased linearly as unsaturation and chain length of infused fatty acids increased. Percentages of fat, CP, and SNF in milk and total tract apparent digestibilities of DM, OM, ADF, NDF, energy, and fatty acids were not affected significantly by treatments. Infusing fatty acids decreased proportions and yields of short- and medium-chain fatty acids and increased proportions and yields of unsaturated C18 fatty acids in milk fat. Increasing unsaturation and chain length of infused fatty acids linearly decreased proportion and yield of palmitic acid but increased proportions and yields of polyunsaturated C18 fatty acids in milk fat. Infusing fatty acids increased concentrations of NEFA and cholesterol in blood plasma. The profile of fatty acids reaching the intestine may be an important determinant of responses to supplemental fats fed to lactating dairy cows. PMID- 1500556 TI - Resistance of fatty acyl amides to degradation and hydrogenation by ruminal microorganisms. AB - Two in vitro trials were conducted to determine whether fatty acyl amides are degraded and hydrogenated by ruminal microorganisms. The treatments consisted of ground hay supplemented with either no lipid, linoleoyl Met ethyl ester, or free linoleic acid plus Met ethyl ester. Incubations were carried out in Erlenmeyer flasks at 39 degrees C under CO2. Cultures were sampled at predetermined times and analyzed for long-chain fatty acids, Met, and VFA. In trial 1, the rate of disappearance of linoleic acid was lower for the amide than for the FFA (.004 and -.047/h, respectively). In trial 2, there were no differences in the rate of disappearance of linoleic acid from 0 to 6 h (-.237 and -.357/h for amide and FFA, respectively), but the rates from 6 to 48 h (-.003 and -.027/h for amide and FFA, respectively) were different. Linoleoyl Met cultures also had higher acetate to propionate ratio and lower loss of Met compared with free linoleic acid cultures. There was no loss of radioactivity from [14C]stearoyl Met after 24 h of incubation, indicating its resistance to bacterial breakdown. The results showed that fatty acyl amides resist bacterial breakdown and prevent loss of double bonds by microbial biohydrogenation. PMID- 1500557 TI - Impact of alfalfa maturity and preservation method on milk production by cows in early lactation. AB - Ninety-six cows in early lactation were used in two experiments to measure the impact of alfalfa maturity (early or midbud vs. early or midbloom) and method of forage preservation (silage vs. hay) on DMI and milk production. Silage diets were fed as TMR, and hay was fed separately from grain. All diets contained 60% alfalfa (dry basis) and were balanced for 19% CP. Maturity had little effect on milk production in either experiment. Adjusted milk production for early cut silage, late cut silage, early cut hay, and late cut hay were 33.6, 33.4, 30.7, and 32.1 kg/d for Experiment 1 and 38.1, 37.0, 35.0 and 35.0 kg/d for Experiment 2. Increased alfalfa maturity tended to reduce DMI. Cows fed the silage diets consumed 1.2 kg more DM and produced an average of 2.1 kg more milk daily in Experiment 1 than those fed the hay diets. All treatment groups consumed similar amounts of DM in Experiment 2; however, cows fed silage produced 2.6 kg/d more milk than those fed hay. Preserving alfalfa as silage and feeding in a TMR to cows in early lactation resulted in greater milk production via increased DMI or improved feed efficiency compared with preserving alfalfa as hay and feeding grain separately. PMID- 1500558 TI - Impact of stage of maturity and method of preservation of alfalfa on digestion in lactating dairy cows. AB - Four multiparous Holstein cows in midlactation were fed 60:40 forage:grain (dry basis) diets containing first-cutting alfalfa harvested at the early bud or early flower stage of maturity. Each of the two maturities was preserved as silage and hay. A 4 x 4 Latin square design experiment (28-d periods) was conducted to measure the impact of alfalfa maturity and method of preservation on milk production and composition, intake, digestion, digesta passage, and particle size of digesta. Milk production and composition were not affected by treatment. Increases in fiber intake resulted from increased maturity and preservation as hay, but this did not appear to limit DMI or milk production. Both increased maturity and preservation as hay resulted in the following effects in cows: more time spent ruminating, greater total chewing time, greater wet and dry rumen fill, and a greater volume of rumen contents. Rumen retention time of La applied to forage was 6 h less, and 0-h disappearance of DM from dacron bags was greater for silage than hay. In situ DM disappearance rates averaged 15%/h for silage and 9.5%/h for hay. Lag time was related inversely to 0-h disappearance. Masticates and mixed rumen samples from cows fed hay showed a greater percentage of DM as particles greater than or equal to 9.5 mm in length. Gross feed efficiency was greater for cows fed alfalfa silage than for those fed alfalfa hay, probably because of more rapid digestion and passage. The potential for rumen fill to limit intake in high producing cows appears to be greater for alfalfa preserved as hay than that preserved as silage. PMID- 1500559 TI - Comparative responses of lactating cows to total mixed rations or computerized individual concentrates feeding. AB - A trial was conducted in a commercial dairy herd in which the concentrate part of the ration was fed individually to a group of cows through computerized self feeders. Performance results were compared with those of a group fed TMR of 65 to 67% concentrates. Rationing of individual concentrates was according to parity, milk yield, milk yield potential, BW changes, and bunk feed-stuffs. Mean intake of concentrates per cow was about 1 kg/d lower in the individually supplemented cows. This was partly compensated for by a higher intake of bunk feedstuffs. Overall daily milk yield per cow was similar to those receiving a TMR in first parity cows, higher in second parity cows, and lower in third and greater parity cows. The higher performance of the second parity cows was achieved in all milk yield potential classes, and the lower yield in subsequent lactations was due to lower performance in low and high potential classes. The individually supplemented cows gained less BW than those in the TMR group. Milk yield per unit of BW was better than milk yield as a variable to refine individual cow supplementation strategy for allocation of concentrates. Results also suggest that the same criteria used for supplementation of concentrates can be beneficial to cows' assignments and movements among different TMR groups. Computerized dispensing of concentrates, when applied properly, can economize on consumption of concentrates when grouping and feeding different TMR are impossible. PMID- 1500560 TI - Estimating production benefits through simulation of group and individual feeding of dairy cows. AB - Objectives were 1) to develop DMI and milk prediction equations, 2) to use these equations to simulate group and individual feeding of dairy herds, and 3) to estimate effects of group and individual feeding on FCM production. University of New Hampshire data were used to predict DMI from previous DMI and cow and ration characteristics. The same data were used to predict milk production from DMI and previous milk production. Feeding was simulated for 100 cows over 50 4-wk periods in a number of trials. Effects of individual feeding, additional groups, herd calving intervals, and within-herd variation of annual milk production per cow on daily FCM per cow were isolated in average and high producing herds. Changing from one group to individual feeding can increase daily FCM per cow by .5 to 1.1 kg and two groups to individual feeding by 0 to .8 kg without changing total herd nutrient intake. Reallocation of the same amount of nutrients to two groups instead of one can increase daily milk production by .15 to .8 kg of FCM per cow, reallocation to three groups instead of two by 0 to .6 kg of FCM per cow, and reallocation to four groups instead of three by 0 to .35 kg of FCM per cow. PMID- 1500561 TI - Influence of feeding varying levels of Amaferm on performance of lactating dairy cows. AB - Amaferm, a fermentation extract of Aspergillus oryzae, was fed as a top-dressing to dairy cows at 0, 1.5, 3, and 6 g/d in two lactation trials using 64 cows in 1989. Lactation trial 1 was conducted in the spring (March to May) and used 40 cows averaging 75 DIM for a 70-d treatment period. Lactation trial 2 was during the summer (June to July). Twenty-four cows averaging 140 DIM were employed in a 60-d study. Measurements included milk yield, feed intake, BW, rectal temperatures, respiration rate, and digestibility of CP, NDF, and DM. None of the levels of Amaferm had a significant effect on milk yield or composition, BW changes, or digestion coefficients in either trial. Cows fed 1.5 g/d of Amaferm had a higher DMI than those receiving 0 or 6 g in trial 1, and respiration rates were significantly higher for cows fed 3 g/d of Amaferm in trial 2. Under the conditions of this study, none of the levels of Amaferm affected the performance of lactating cows. Further elucidation of factors influencing response to Amaferm is needed. PMID- 1500562 TI - Metabolic changes in dairy cows with ketonemia in response to feed restriction and dietary 1,3-butanediol. AB - The objective was to measure progressive changes in metabolism of cows during a protocol that induced subclinical ketosis. From d 14 to 42 postpartum, 13 Holstein cows were in either a control group (6 cows) or a ketosis induction group (7 cows) that was restricted to 80% of ad libitum intake and fed 1,3 butanediol (7% of DM). Six ketosis induction cows developed ketonemia but not clinical ketosis; cow 7 developed clinical ketosis. Milk production was less, but fat content was greater, for ketonemic cows. Energy balance reached a nadir of 7.2 Mcal/d at d 21 for ketonemic cows, whereas controls reached energy equilibrium at d 28. Concentrations of NEFA in plasma and of beta-hydroxybutyrate in whole blood increased during ketonemia. Dextran sulfate-precipitable cholesterol and triglyceride in serum were increased only at d 21 and not at d 28, 35, 42, or 49. Concentrations of glycogen, total lipid, triglyceride, and cholesterol in liver increased during ketonemia. Oxidation of palmitate to CO2 was greater at d 21 in liver slices from ketonemic cows, whereas oxidation to acid-soluble products remained constant for those cows but decreased for controls. The ketonemic cows had lower weight ratios of triglyceride to glycogen in liver during pretreatment than those that became clinically ketotic in earlier studies (.5 vs. greater than or equal to 1.8). Susceptibility to clinical ketosis, therefore, may be indicated by increased hepatic triglyceride to glycogen ratios during the peripartal period. PMID- 1500563 TI - Neutrophil and lymphocyte response to supplementation with vitamins C and E in young calves. AB - Calves, beginning at 3 d of age, were bottle-fed milk replacer unsupplemented, or supplemented with 10 g of vitamin C, or supplemented with 10 g of vitamin C plus 57 IU of vitamin E/kg of dry milk replacer (10 calves per treatment). Neutrophils from wk 2 and 4 blood samples were assayed for Staphylococcus aureus phagocytosis and neutrophil-mediated, antibody-dependent cellular cytotoxicity, and lymphocytes from those samples were assayed for concanavalin A-induced, phytohemagglutinin-induced, or pokeweed mitogen-induced proliferation. Ocular and nasal discharges of calves supplemented with vitamins C or C and E were less than those of controls for wk 1 to 8. Calves receiving supplementation with vitamin C and E tended to have higher mitogen-induced lymphocyte proliferative responses at wk 2. Neutrophil-mediated phagocytosis and antibody-dependent cellular cytotoxicity were lower at wk 2 and 4 for calves supplemented with vitamin C than for controls. Neutrophil function of calves supplemented with vitamins C and E together was near, or slightly higher than, that of unsupplemented calves for wk 2 and 4, suggesting that the addition of vitamin E negated the adverse effects that vitamin C alone had on neutrophil functions. PMID- 1500564 TI - Production performance and physiological responses of Angora goat kids fed acidified milk replacer. AB - Angora kids were blocked by birth weight and sex and assigned randomly to goat milk or acidified milk replacer. Daily milk intake, weekly BW, and heart girth measurements, and blood parameters (packed cell volume, total protein, glucose, and NEFA) were monitored at 3 d (initial) and at 4, 6, 8, and 9 wk of age. Both groups were fed their respective milks for ad libitum intake for 6 wk and then reduced to 75, 50, 25, and 0% of wk-6 intake during wk 7, 8, 9, and 10, respectively. Solid feed (20% CP and 3.1. Mcal of metabolizable energy/kg of DM) was provided for ad libitum intake starting on wk 3. Pretreatment BW (average 2.4 kg) and blood parameters were similar for milk and replacer groups. Packed cell volume (21.8 and 34.2%), total protein (50.3 and 46.6 g/L), and NEFA (.52 and .69 meq/L) for goat milk and acidified milk replacer groups, respectively, were affected by dietary treatment. Final BW (average 10.5 kg) and mean plasma glucose concentration (84 to 88 mg/dl) were similar between treatments; however, kids fed goat milk produced more mohair (13.8%) than those fed acidified milk replacer. Despite physiological differences, acidified milk replacer can be used successfully to raise Angora kids. PMID- 1500565 TI - Potential improvements in rate of genetic gain from marker-assisted selection in dairy cattle breeding schemes. AB - The value of marker-assisted selection in dairy cattle breeding schemes is predicted by a deterministic model. In these schemes, associations between markers and milk production were assessed from production records of daughters of a grandsire by a multiple regression model with random marker effects. By tracing markers from the grandsire to grandoffspring, deviations of grandoffspring from their full-sib family mean were predicted. Predictions of the within-family variance of the grandoffspring accounted for by markers amounted to up to 13.3%. This figure decreased when the number of daughters of the grandsire analyzed decreased and, less markedly, when the distance between flanking markers increased. Prediction of within-family deviations hardly improved rates of genetic gain in conventional progeny testing schemes; equal numbers of young bulls were born annually. Genetic gain and improvement of genetic gain because of prediction of within-family deviations were much higher in nucleus schemes. In these shemes, with short optimized generation intervals, conventional selection was mainly for pedigree information and did not use the within-family variance. Analysis of highly polymorphic markers in daughters of both grandsires accounted for 4.1 to 13.3% of the within-family variance, which increased rates of gain by 9.5 to 25.8% and 7.7 to 22.4% in open and closed nucleus schemes, respectively. Risk of breeding schemes, measured by the variance of the selection response, was not increased by the use of markers. PMID- 1500567 TI - Estimating milk, fat, and protein lactation curves with a test day model. AB - Test day models were used to estimate lactation curves for milk, fat, protein, fat percentage, and protein percentage and to study the influence of age, season, and herd productivity on Holstein lactation curves. Random effects of lactation within herd and fixed effects of herd test date were absorbed. Fixed effects of cow's age on test day and either DIM (57 divisions) by parity (1, 2, greater than or equal to 3) class or season of calving (winter or summer) by DIM by parity class were estimated. Lactation curves for yield traits derived from DIM solutions were flatter for first versus later lactation, even without addition of age effects. Differences between lactation curves for the two seasons were slight, suggesting that most observed seasonal differences are caused by seasonal productivity accounted for by herd test date effects. At peak, winter calving cows yielded slightly more milk of similar fat percentage but of lower protein percentage than those calving in summer. Data were also partitioned into nine subsets based on rolling herd milk and fat percentage. Lactation curves for yield traits, but not percentage traits, varied with rolling herd milk. Lactation curves for fat yield and percentage varied with rolling herd fat percentage. PMID- 1500566 TI - Relationship of in vitro immune function with health and production in Holstein cattle. AB - Eighty-seven lactating Holstein cows from the Iowa State University Breeding Research Herd were evaluated for 20 in vitro measures of immune function. Principal component analysis was used to discard redundant assay variables such that the 11 remaining variables were more nearly independent than the original variables. Multiple linear regression in an animal model was used to determine the effects of these 11 variables on lifetime production and on general, under, and reproductive health traits. A significant joint effect of the 11 immune function variables on California mastitis test scores was observed. California mastitis test scores were positively correlated with antibody-dependent neutrophil cytotoxicity and negatively correlated with antibody-independent neutrophil cytotoxicity. Wisconsin mastitis test scores were also positively associated with antibody-dependent neutrophil cytotoxicity. Cytochrome c reduction was negatively associated with mammary and total health costs. A positive relationship between clinical mastitis and discarded milk and IgG2 was observed, and IgG1 was associated with increased quarter California mastitis test scores and increased production. Thus, certain in vitro immune function assays may serve as indicators of susceptibility to health problems in dairy cattle, particularly for traits associated with udder health. PMID- 1500568 TI - Estimates of repeatability of reproductive measures in Canadian Holsteins. AB - Repeatabilities and heritabilities of days to first service, days open, and number of services per conception were estimated from 235,589 records on 80,333 Holstein cows, daughters of 306 sires obtained from the Quebec Dairy Herd Analysis Service, by REML. The model for statistical analyses included herd-year season as a fixed effect and sire, cow (sire's daughter) within sire, and error as random effects. Variance components corresponding to sire, cow within sire, and error were then estimated by REML. Heritability estimates, obtained from the sire variance component, were .03, .05, and .03 for days to first service, days open, and number of services per conception, respectively. Repeatability estimates, obtained from the sire and cow within sire variance components were .08, .10, and .07 for days to first service, days open, and number of services per conception, respectively. PMID- 1500569 TI - Evaluation of postmilking teat germicides containing Lauricidin, saturated fatty acids, and lactic acid. AB - The efficacies of postmilking teat germicides containing Lauricidin (glyceryl monolaurate), saturated fatty acids, lactic acid, and lauric acid were determined against new IMI caused by Staphylococcus aureus and Streptococcus agalactiae in three controlled infection trials. In trial 1, a germicide was evaluated containing 1% Lauricidin, 5% caprylic and capric acids, 6% lactic acid, and .85% lauric acid. New IMI with Staph. aureus and Strep. agalactiae were reduced 81.3 and 49.6%, respectively. Trial 2 germicide involved an artificially aged sample of the formulation evaluated in trial 1. The germicide was aged at 40 degrees C for 5 mo, which was approximately equal to 2 yr at room temperature (24 degrees C). Reductions in new IMI were 81.2 and 27.5% for Staph. aureus and Strep. agalactiae, respectively. In trial 3, a teat germicide aged at ambient temperature for 33 mo, which was originally formulated to contain 1% Lauricidin, 5% caprylic and capric acids, and 6% lactic acid, was evaluated. Reductions in new IMI were 75.5 and 40.4% for Staph. aureus and Strep. agalactiae, respectively. The formulation evaluated in trial 1 was superior to other formulations in reducing new IMI by the two test organisms. PMID- 1500570 TI - Extension factors for incomplete lactations of Serra-da-Estrela sheep. AB - Data for 6537 lactations of 2335 Serra-da-Estrela ewes representing 41 flocks (1966 to 1985) were obtained from the Milk Recording Scheme conducted by the Portuguese Ministry of Agriculture. The suckling period averaged 32 d, and ewes were milked for approximately 200 d after the suckling period. Individual test day yields for 1548 lactations of 600 ewes from 32 flocks (1975 to 1985) were used to define the shape of the lactation curve. A third-order polynomial and an exponential function were equally accurate in describing the shape of the lactation curve in the postsuckling period. A considerable number of incompletely recorded lactations occur, and, with extension factors, these incomplete lactations could be used in genetic evaluation. Factors based on both partial lactation yield and last test day yield were developed. Use of these factors should be restricted to partial lactations of at least 75 d with 2 test days. An alternative of recording only postweaning yield was proposed. PMID- 1500571 TI - Effect of direct-fed microbials on rumen microbial fermentation. AB - Nonbacterial, direct-fed microbials added to ruminant diets generally consist of Aspergillus oryzae fermentation extract, or Saccharomyces cerevisiae cultures, or both. Results from in vivo research have been variable regarding effects of direct-fed microbials on ruminant feedstuff utilization and performance. Some research has shown increased weight gains, milk production, and total tract digestibility of feed components, but others have shown little influence of direct-fed microbials on these parameters. In vitro research with mixed ruminal microorganisms likewise has been inconsistent regarding the effects of direct-fed microbials. Several researchers observed that direct-fed microbials increased cellulolytic bacterial numbers in the rumen and stimulated the production of some fermentation end products. This suggests that direct-fed microbials may be providing growth factors for the ruminal microbes. However, other researchers have reported no effect of direct-fed microbials on in vitro fiber digestion. Recent research demonstrated that growth of the predominant ruminal bacterium Selenomonas ruminantium in lactate medium as well as lactate uptake by whole cells of Sel. ruminantium were markedly increased by an A. oryzae fermentation extract and an S. cerevisiae culture. In addition, both products increased the production of acetate, propionate, succinate, total VFA, and cell yield (grams of cells per mole of lactate). Therefore, it appears that these direct-fed microbials provide soluble factors that stimulate lactate utilization by Sel. ruminantium. Evidence is presented indicating that the malate content of the A. oryzae fermentation extract and S. cerevisiae culture may be involved in this stimulation. PMID- 1500572 TI - Bacteriophage resistance in Lactococcus lactis ssp. lactis using antisense ribonucleic acid. AB - Antisense RNA against a conserved bacteriophage gene when expressed in a Lactococcus lactis ssp. lactis strain renders it resistant to bacteriophage infection. Two open reading frames have been identified in a L. lactis ssp. lactis bacteriophage that are conserved in a majority of isolates. They code for an 18-kDa (designated GP18C) protein and a 24-kDa (GP24C) protein, respectively, which are arranged along with previously identified open reading frames in a tandem motif similar to other bacteriophages. The presence of gp18C and gp24C in a number of bacteriophage isolates was confirmed by polymerase chain reaction using primers specific for these regions. Plasmids bearing various fragments of gp18C, gp24C, or both were constructed such that the respective open reading frames were positioned in the antisense direction relative to the Lactococcus lactis ssp. cremoris Wg2 promoter, p59. These antisense RNA-producing vectors inhibited the efficiency of plaquing of L. lactis ssp. lactis bacteriophage phi 7 9 up to 50%; the resulting plaques were extremely small and irregular in shape. The replication of the bacteriophage was severely inhibited, and the total number decreased over the first 3 h during infection in strains expressing antisense RNA compared with the host strain alone, in which the bacteriophage number increased 10(4)-fold. PMID- 1500573 TI - Variations and distributions of O-glycosidically linked sugar chains in bovine kappa-casein. AB - The variation and distribution of O-glycosidically linked sugar chains in kappa casein from bovine mature milk were analyzed by HPLC, fast atom bombardment mass spectrometry, and 13C nuclear magnetic resonance. A monosaccharide alditol (N acetylgalactosaminitol) and four oligosaccharide alditols [a neutral disaccharide (galactosyl-beta 1-3N-acetylgalactosaminitol), two acidic trisaccharides (straight chain: N-acetylneuraminyl alpha 2-3galactosyl-beta 1-3N acetylgalactosaminitol and branch chain: galactosyl beta 1-3(N-acetylneuraminyl alpha 2-6)N-acetylgalactosaminitol), and an acidic tetrasaccharide(N acetylneuraminyl alpha 2-3galactosyl-beta 1-3(N-acetylgalactosaminyl alpha 2-6)N acetylgalactosaminitol] were identified as sugar chains linking on normal bovine kappa-casein. The most dominant sugar chain was an acidic tetrasaccharide. The four oligosaccharide chains were identical to those already found, but N acetylgalactosamine was a newly identified sugar chain linking on kappa-casein. The distribution of monosaccharide, disaccharide, trisaccharide (straight), trisaccharide (branched), and tetrasaccharide chains were determined by HPLC to be .8, 6.3, 18.4, 18.5, and 56.0%, respectively (means of five kappa-caseins). PMID- 1500574 TI - Effect of a prolonged-release formation of N-methionyl bovine somatotropin (sometribove) on milk composition. AB - Forty Holstein cows received bi-weekly injections of prolonged-release formulation of bST, and 39 received bi-weekly injections of excipient, in a study to evaluate the effects of long-term bST administration on milk composition and component production. Injections began at 60 +/- 3 d postpartum. Administration of bST increased production of milk and of all measured components. Concentrations of lactose (4.85 and 4.81%), fat (3.76 and 3.67%), total solids (12.57 and 12.44%), SNF (8.83 and 8.75%), casein (2.56 and 2.53%), and true protein (3.13 and 3.08%) were similar in milks from cows receiving bST and excipient, respectively. Percentages of NPN (times 6.38) and total protein were greater in milk from bST-treated cows (.179% NPN and 3.32% total protein) compared with milk from cows injected with excipient (.172% NPN and 3.24% total protein). Use of bST did not change the relative percentages of alpha s-casein, beta-casein, kappa-casein, beta-lactoglobulin, alpha-lactalbumin, or casein proteolysis products. A cyclical pattern of milk production, component production, and composition within each 14-d injection interval was observed. This suggests that a diminishing amount of bST was delivered during the latter third of each injection interval. There were no effects of bST on milk composition that would be of any practical significance to dairy product manufacturers or consumers. PMID- 1500575 TI - Effect of a prolonged-release formulation of N-methionyl bovine somatotropin (sometribove) on milk fat. AB - Nine Holstein cows were injected bi-weekly with a prolonged-release formulation of N-methionyl bST, and 9 cows were injected with excipient. Intramuscular injections began at 60 +/- 3 d postpartum and continued at 14-d intervals for the full lactation. Administration of bST increased production of milk, total fat, and all milk fat components measured. Average fatty acid composition of milk fat was not influenced by bST treatment. Stage of lactation had a large influence on production and percentage of individual fatty acids in milk fat from both bST treated and control cows. The stage of lactation impact on the fatty acid composition of milk fat reflected changes in the relative contributions of body fat mobilization and de novo synthesis of milk fat components in response to changes in energy balance. Initiation of bST treatment caused some transient changes in milk fatty acid composition that were related to energy balance. These changes were small compared with the normal changes because of stage of lactation in all cows. Phospholipid and cholesterol content of milk also changed with stage of lactation but were not influenced by bST treatment. Melting properties of milk fat were influenced greatly by stage of lactation. Bovine somatotropin did not cause any changes in composition or physical properties of milk fat that were outside the range of normal variation. PMID- 1500576 TI - Nonspecific antibacterial factors in milk from cows immunized with human oral bacterial pathogens. AB - Both the immunoglobulins and non-specific antibacterial factors in milk from cows immunized with pathogenic oral bacteria have the potential to influence the oral microflora during passive immunization studies. The first six milks after calving were collected from 2 cows immunized with adjuvant and from 14 cows immunized with adjuvant and heat-killed strains of periodontopathic Actinomyces, Porphyromonas, Prevotella, and Fusobacterium. Analysis of the products from the first to the sixth milks revealed that the protein and lysozyme content decreased approximately 66 and 72%, respectively; the mean specific activity of the enzyme remained relatively constant. In contrast, the mean lactoperoxidase activity increased 2.3-fold in the second milking and increased further in the fourth and sixth milkings. The mean iron-binding activity increased 1.2-fold from the first to the second milkings and then decreased 3.6-fold through the sixth milking. Cows immunized with adjuvant alone showed similar responses. Per unit volume, the milk contained approximately 150 times less lysozyme than whole human saliva obtained from six subjects but higher concentrations of lactoperoxidase and iron binding components. Purified bovine nonspecific factors prevented the growth of the bacteria used for immunization when bacteria were tested at concentrations similar to those found in saliva and milk. Because bovine nonspecific antibacterial factors could influence both the pathogenic target bacteria and the indigenous microflora in oral passive immunization studies with bovine immunoglobulins, the presence of these proteins should be considered. PMID- 1500577 TI - Antigenic homology of endotoxin with a coliform mastitis vaccine strain, Escherichia coli O111:B4 (J5). AB - This study examined recognition of heterologous Gram-negative endotoxin by antibodies recognizing common lipopolysaccharide core antigens. Gram-negative endotoxins from 11 heterologous bacterial strains were tested for recognition by antibodies against common lipopolysaccharide core antigens. Serum was harvested from a calf immunized with the Rc mutant, Escherichia coli O111:B4 (J5), and affinity purified against endotoxin derived from an Ra mutant, Salmonella typhimurium, producing an antibody reagent recognizing homologous Gram-negative core antigens present in the Rc mutant vaccinal antigen. This reagent demonstrated reactivity against 11 chemically purified Gram-negative endotoxins. Included were endotoxins derived from 3 smooth E. coli species, 2 Salmonella spp., Shigella flexneri, Klebsiella pneumoniae, Pseudomonas aeruginosa, Serratia marcescens, and lipid A. Endotoxin derived from K. pneumoniae had significantly higher ELISA reactivity with core antigen specific antibodies than did endotoxin derived from either E. coli O111:B4 (J5) or P. aeruginosa. These results suggest immunization with R mutant bacterins may have utility in the prevention of Gram negative mastitis even when whole bacteria react poorly with antibodies recognizing common core antigens. PMID- 1500578 TI - Kinetics and characteristics of bovine neutrophil alkaline phosphatase during acute Escherichia coli mastitis. AB - Alkaline phosphatase activity of isolated bovine blood neutrophils was investigated before and during experimentally induced Escherichia coli mastitis. Activities markedly increased 1 wk after infection in neutrophils of cows suffering from moderate or from severe disease. Elevated neutrophil alkaline phosphatase activity did not correlate with a specific stage of maturating postmitotic neutrophils appearing in circulation during mastitis. Neutrophil alkaline phosphatase from healthy cows before infection and from mastitic cows was characterized by means of thermostability, specific inhibitor patterns, slab gel electrophoresis, and kinetic parameter analysis. The leukocyte enzyme from healthy and mastitic cows displayed very similar characteristics, suggesting that the increase in activity during mastitis is most probably related to the enhanced expression of the normal alkaline phosphatase enzyme. PMID- 1500579 TI - Prevalence of Staphylococcus species during the periparturient period in primiparous and multiparous cows. AB - During a 14-mo period, 77 multiparous and 36 primiparous cows were sampled to determine the prevalence of staphylococci during the periparturient period. Distal streak canal swabs were taken at 14 d prepartum, and foremilk was sampled the first 5 consecutive wk of lactation. Staphylococcus aureus was isolated from 7.6% of quarters of primiparous cows but from only .6% of quarters of multiparous cows at parturition. Prevalence in primiparous cows declined to 3.5% by the wk-1 sampling. Quarter prevalence of coagulase-negative Staphylococcus species prepartum, at parturition, and wk 1 to 5 in primiparous cows was 38.9, 27.8, 15.3, 14.6, 13.2, 15.3, and 14.6%, respectively. In multiparous cows, prevalence at these times was 50.3, 12.3, 6.2, 8.1, 10.7, 7.1, and 8.1%. Staphylococcus chromogenes was the predominant species isolated, accounting for over 50% of the staphylococci isolated at each sampling time. Results suggest that high prevalence of staphylococci isolated prepartum is a reflection of natural skin flora and that a higher postpartum prevalence of these organisms was observed in primiparous cows than in multiparous cows. These data suggest also that the peripartum heifer could be a source of Staphylococcus aureus in the lactating herd. PMID- 1500580 TI - Prediction of mastitis using milk somatic cell count, N-acetyl-beta-D glucosaminidase, and lactose. AB - The objectives of this work were 1) to examine the responsiveness of SCC, lactose concentration, and NAGase activity in milk to changes in bacteriological status and 2) to develop models for predicting bacteriological status of mammary glands. Data included 550 cows in 10 commercial herds. Natural logarithm NAGase and log cell count were most responsive to changes in bacterial status. The log NAGase was relatively more effective in identifying major from minor pathogen infections, whereas log SCC was better able to differentiate between infected and uninfected classes. Non-transformed NAGase, SCC, and lactose were considerably less responsive to infection status. Logistic regression of bacterial status on herd, lactation number, milk, log SCC, log NAGase, and stage of lactation was performed. The least significant variables were removed in a stepwise process. Final predictors of infection status were herd, log SCC, and log NAGase. The role of log SCC was to discriminate infection from no infection, whereas log NAGase discriminated major from minor pathogens. The log NAGase, alone or in combination with log SCC, added substantially to the detection power of the model. Chi-square goodness of fit tests found no significant differences between observed and predicted infection probabilities. Substitution of herd averages for log SCC and log NAGase for the herd variables resulted in significant differences between predicted and observed herd infection probabilities. PMID- 1500581 TI - Influence of involution on intramammary phagocytic defense mechanisms. AB - Mammary secretions (n = 34 cows) and mammary phagocytes (n = 18 cows) were collected throughout the nonlactating (dry) period to determine changes in intramammary phagocytic defense mechanisms. Mammary secretions were evaluated for their ability to support phagocytosis of Staphylococcus aureus by neutrophils from donor cows and mammary phagocytes for phagocytic and chemiluminescence activity. Ability of secretions to support phagocytosis decreased with advancing length of the dry period. This effect was more pronounced when dry cow secretions constituted 50% of the phagocytic mixture. Phagocytic activity of mammary phagocytes decreased with advancing dry period when autologous secretion was used in the incubation mixture. With homologous secretion, the percentage of phagocytosis increased 5 to 6 d after drying off compared with before drying off and then gradually decreased throughout the remainder of the dry period. Chemiluminescence activity (log10 counts per minute) of mammary phagocytes was lower during the dry period and decreased with advancing dry period. Results indicated diminishing ability of secretions to support phagocytosis and diminished phagocytic and bactericidal mechanisms during the dry period. PMID- 1500582 TI - Casein, actin, and tubulin expression during early involution in bovine and murine mammary tissue. AB - Hybridization methods and in vitro translation were used to examine the expression and functional condition of messenger RNA encoding caseins and cytoskeletal proteins in the mammary gland during early involution. In the mouse, steady state mRNA levels for alpha-, beta-, and gamma-caseins coordinately decreased to 20% of initial levels between 12 and 72 h after pup removal. In vitro translatability of mouse casein mRNA, as determined by immunoprecipitation, electrophoresis, and gel slice counting, revealed a pattern that closely paralleled mRNA expression. In contrast, bovine casein mRNA levels were only slightly reduced by 72 h postmilking, whereas in vitro translatability decreased by about one-half. Northern blot analysis of total mouse mammary RNA that were hybridized with probes to cytoskeletal proteins showed a gradual decrease of alpha-tubulin mRNA, but an increase in beta-actin mRNA during early involution. Two-dimensional gel analysis of in vitro translated products indicated a concordant increase in beta-gamma-actin. In the cow, beta-actin mRNA at 72 h of involution was equal to or greater than that during lactation. These results demonstrate the generally slower involution response in the cow and suggest that differing regulations are involved. Early events of cellular involution may be related to a reorganization of the cytoskeleton. PMID- 1500583 TI - Depletion of intramuscularly injected ceftiofur from the milk of dairy cattle. AB - Ceftiofur sodium, a new broad-spectrum cephalosporin, has been approved in the US, Canada, and several other countries throughout the world to treat bovine respiratory disease in cattle and dairy cows. In Experiment 1, 6 lactating cows were intramuscularly treated with 2.29 mg of [14C]ceftiofur/kg of BW daily for 5 d. In Experiment 2, 30 additional cows at three locations were similarly treated with 2.2 mg of ceftiofur (unlabeled)/kg of BW. Milk was collected every 12 and 24 h after each dose and every 12 h up to 5 d after the last dose. The majority of milk samples, both during treatment (12 and 24 h after each dose) and after the last dose (up to 5 d following ceftiofur treatment), were negative by screening procedures based on microbial inhibition (Delvotest-P, Bacillus stearothermophilus disk assay, and cylinder plate assays). The receptor-binding Charm Test II assay, which has a limit of detection of .005 ppm of ceftiofur, gave positive tests for milk samples up to 48 h following treatment. When the Charm Test II assay is used with .008 IU/ml of penicillin as a positive control, 44% of the samples from individual cows were negative at 12 h posttreatment. Ninety percent of the samples from individual cows were negative at 24 h after the last treatment. The use of ceftiofur in dairy cattle in accordance with the label directions does not result in total residues in milk higher than the FDA calculated safe concentration of 1-ppm ceftiofur equivalents. The milk from individual cows did not test positive by the commercial screening assays examined in this study, except for the Charm Test II. The Charm Test II was 90% negative using the Charm Sciences criteria at 24 h after the last treatment. PMID- 1500584 TI - Effects of late gestation heat stress on postpartum milk production and reproduction in dairy cattle. AB - Carry-over effects of late gestation heat stress on postpartum productive and reproductive traits were estimated from DHI records using 341 lactations from six sites in Mississippi. Climatological data were gathered from records of weather stations near the sites. Using multiple linear regression analyses, predictor variables for lactations were age at calving, lactation number, maximum degree days (above 32.2 degrees C) during the periods 30 and 60 d prepartum, and precipitation 30 and 60 d prepartum. Months and sites were indicator variables. Dependent variables included milk and fat production during early, mid, and late lactation; days to peak lactation; days open; services per conception; and body weight. Age at calving affected milk and fat production in mid and late lactation and services per conception. Degree-days for 60 d prepartum had the greatest negative influence on production variables; its statistical significance was shown in predictions of milk and fat production in early and midlactation. Days open were higher for July than for cows calving in August or September. Sites had effects on many milk and fat measurements and some reproductive traits. These results indicate that heat stress in the last 60 d of gestation has negative effects on some production variables. PMID- 1500585 TI - Milk yields and hormone concentrations of Holstein cows in response to sometribove (somatotropin) treatment during the dry period. AB - Holstein cows (n = 135) under commercial management were used to determine whether sometribove (recombinant methionyl bST, 25 mg/d) administered during the dry period affected milk yield during the ensuing lactation. Cows scheduled to begin lactations (greater than or equal to 2) during January to March were assigned randomly to treatments of sodium bicarbonate excipient (n = 67) or bST (25 mg/d, n = 68). Subcutaneous injections were given for 14 d, corresponding to d -21 to -7 relative to expected calving date. Days dry prior to first injection (64.0, 60.2) and number of injections received (13.9, 13.8) were similar for control and treatment groups, but days from last injection to calving (8.8, 7.1) differed. No differences in incidence of dystocia or udder edema were detected. Previous lactation yields were 8251 and 7952 kg, and yields for lactations following treatment were 8328 and 7852 kg, based on complete lactation data. Mean test date 3.5% FCM yields for control and treated groups during experimental lactation differed before (30.3 vs. 28.1 kg) but not after (29.5 vs. 28.4 kg) covariance adjustment for previous total lactation milk yield. Test of heterogeneity of regression provided no evidence that respective curves for FCM yield during lactation were not parallel or of different magnitude. Elevation of serum bST during 2 wk of the dry period resulted in no apparent increase in extent of mammogenesis or lactogenesis that was translated into an increase in milk yield. PMID- 1500586 TI - Time series cross-correlation analysis of postparturient relationships among serum metabolites and yield variables in Holstein cows. AB - Time series cross-correlation analysis was used to determine relationships among serum beta-hydroxybutyrate, glucose, FFA, cholesterol, milk yield, DMI, and estimated net energy balance for 42 d postpartum for 14 multiparous cows. Milk yield was positively associated with beta-hydroxybutyrate concentrations on the same day, and milk yield was a primary determinant of metabolic change. Dry matter intake was negatively correlated with beta-hydroxybutyrate concentrations 3 d later and on the same day. The data supported in vitro studies showing that FFA are positively associated with beta-hydroxybutyrate production, showed that glucose concentrations are negatively cross-correlated with beta-hydroxybutyrate concentrations, and found that estimated net energy balance is negatively cross correlated with beta-hydroxybutyrate. Analyses suggested that serum glucose and cholesterol concentrations significantly decreased with increased milk yield; analyses also suggested that elevated beta-hydroxybutyrate concentrations were associated with decreases in milk yield 6 d later. beta-Hydroxybutyrate and FFA concentrations 3 to 9 d before parturition were positively related to cholesterol concentrations, and relationships were positive between estimated net energy balance and cholesterol, suggesting that cholesterol concentrations increased as precursors for cholesterol synthesis were available. Time series cross correlation analysis was a useful tool in examining relationships among variables when repeated samples were obtained from the same individuals. PMID- 1500587 TI - Effect of prepartum dry matter intake on liver triglyceride concentration and early lactation. AB - Depression in feed intake during the final week before calving was hypothesized to be a major factor in the etiology of fatty liver development near parturition. Eleven cows were allowed to eat for ad libitum intake prior to calving (control), and 11 cows were maintained at the same level of DMI recorded during d 21 to 17 prior to calving by force feeding the feed refusals via rumen cannulas. Feed intake by control cows decreased 28% during the final 17 d prior to calving. Lipid triglyceride increased 227 and 75% for control and force-fed cows between d 17 prior to parturition and d 1 following calving. Dry matter intake prior to calving was correlated negatively with liver triglyceride immediately after calving (r = -.80). Plasma glucose concentrations for control and force-fed cows were 63 and 76 mg/dl 2 d prior to calving and also were related closely to liver triglyceride immediately after calving (r = -.50). By d 28 after calving, there were no differences in liver triglyceride between treatments. Cows that were force-fed prior to calving tended to yield milk with greater fat percentage (4.22 vs. 3.88%) and to yield more 3.5% FCM (46.1 vs. 41.7 kg/d) during the first 28 d postpartum. PMID- 1500588 TI - Effects of feeding lactating dairy cows diets containing whole soybeans and tallow. AB - Four multiparous Holstein cows averaging 133 d postpartum and fitted with ruminal cannulas were utilized in a 4 x 4 Latin square design to investigate the effects of feeding diets containing whole soybeans and tallow. Treatments were 1) control, no added fat; 2) control and 10% whole raw soybeans; 3) control, 10% whole raw soybeans, and 2.5% tallow; and 4) control, 10% whole raw soybeans, and 4.0% tallow. Cows were fed for ad libitum intake a diet of alfalfa haylage, corn silage, and concentrate (45:5:50, DM basis). Intakes of DM and production of milk, milk CP, milk SNF, and 4% FCM were not affected by feeding supplemental fat. Production of milk fat and weight percentages and yields of long-chain fatty acids in milk fat were increased, whereas weight percentages and yields of short- and medium-chain fatty acids were decreased by feeding supplemental fat. Digestibilities of DM, OM, energy, cellulose, and fatty acids were decreased slightly when fat was added to the diet, but utilization of energy and N for production of milk was not altered. Supplemental fats increased concentrations of NEFA and cholesterol in plasma. These data indicate that relatively large amounts of unprotected fat can be added to the diet of lactating dairy cows without deleterious effects on milk composition, ruminal fermentation, or nutrient digestibilities. PMID- 1500589 TI - Lactational responses of dairy cows fed unsaturated dietary fat and receiving bovine somatotropin. AB - Feeding unsaturated dietary fat to lactating dairy cows receiving bST may effectively alter the fatty acid composition of milk fat. This was tested using 16 Holstein cows assigned to one of four treatments during midlactation. Treatments were control, control diet with 15.5 mg of bST/d per cow, dietary fat from sunflower seeds and bST, or dietary fat from safflower seeds and bST. Diets were formulated to contain 19% CP and contained 25% corn silage, 25% alfalfa hay, and 50% concentrate mix on a DM basis. Milk yield was not significantly higher when bST was administered and increased with added fat diets (29.5, 32.7, 40.0, and 34.1 kg/d for the control, control with bST, sunflower seed with bST, and safflower seed with bST treatments, respectively). Percentage of milk fat was similar for all treatments. Concentrations of long-chain and unsaturated fatty acids in milk were increased slightly by bST and substantially with added fat. Milk protein percentages were not influenced by bST but were reduced by approximately .2 unit with added fat. Added unsaturated dietary fat coupled with bST increased milk yield and produced a greater concentration of unsaturated fatty acids in milk. PMID- 1500591 TI - Disappearance of phosphorus in phytate from concentrates in vitro and from rations fed to lactating dairy cows. AB - Objectives were to determine concentrations of P in phytate in selected concentrates, disappearance of P in phytate from these concentrates in vitro, and extent of hydrolysis of phytate in vivo. Total P and P in phytate were determined for eight concentrates; 32 to 81% of total P was in phytate. Six concentrates were incubated in vitro to determine the extent of phytate disappearance from solids and its appearance and disappearance from solution. Greater than 90% of P in phytate disappeared from solids between 6 and 8 h of incubation in vitro (wheat middlings, rice bran, hominy, soybean meal, and dried distillers grains) or between 12 and 24 h (cottonseed meal). Phosphorus in phytate in solution was hydrolyzed by 12 h except for cottonseed meal (by 24 h). Hydrolysis of the inositol ring to release P in vivo was greater than 99%, based on total fecal collection from 11 cows and the use of Cr as an indigestible marker in excreta, and between 94 to 98% for the same samples when acid detergent lignin was used as an indigestible marker to calculate phytate disappearance. These results further indicate that P in phytate should be considered available to lactating dairy cows when rations to meet their P requirements are being formulated. PMID- 1500590 TI - Responses of dairy cows to additions of distillers dried grains with solubles in alfalfa-based diets. AB - Twenty-four Holstein cows in wk 3 through 12 of lactation were used to evaluate distillers dried grains with solubles as a protein source for alfalfa-based diets. Diets were formulated containing 0, 10.1, 20.8, or 31.5% distillers dried grains with solubles. Crude protein in these diets was 13.9, 16.0, 18.1, and 20.3%. Milk yield increased linearly with increasing dietary CP, whereas DMI was not affected. Dry matter intake averaged over 4% of BW for all treatments. Intake of undegraded intake protein was .93, 1.27, 1.63, and 1.97 kg/d. Yields of milk protein, casein, and lactose all increased linearly with increasing dietary CP. The proportion of milk N as whey N decreased, whereas N as NPN increased, with increasing dietary CP. Plasma urea N and essential and branched-chain AA increased linearly, and nonessential AA decreased linearly, with increasing dietary CP. Increasing the concentration of CP in the diet from 13.9 to 18.1% by the addition of distillers dried grains with solubles was beneficial to cows fed alfalfa-based diets in early lactation. Little additional benefit was observed by feeding greater than 18.1% dietary CP. PMID- 1500592 TI - Genetic parameters of conformation traits, milk yield, and herd life in Holsteins. AB - Genetic parameters were estimated simultaneously for 5 herd-life traits, 15 conformation (type) traits, and milk yield measured in first lactation for 128,601 Holstein cows. Heritabilities of all traits were higher in registered than in grade cows. Genetic correlations of linear type traits with first lactation yield ranged from -.48 for udder depth to .54 for dairy form. Genetic correlations among milk yield and herd-life traits were all positive except for milk-corrected herd life in grade cows. Udder traits had largest absolute genetic correlations with herd-life traits, followed by body traits and feet and leg traits. Some traits associated with body size and foot angle differed between registered and grade cows. Estimates of genetic trends from obtained parameters revealed greatest progress for milk yield from single-trait selection but also the largest changes for some type traits and milk-corrected herd life in an undesirable direction. Relative milk to type ratios of between 2:1 and 3:1 yielded 90% of the gain in milk yield with no change or slight improvement in type traits and functional herd life. Selection for type traits associated with herd life appears to be warranted to improve days of functional herd life or to decrease involuntary culling of dairy cows. PMID- 1500593 TI - Relationship between genetic merit of Holstein bulls and deficiency of uridine-5' monophosphate synthase. AB - Heterozygotes for a deficiency of uridine-5'-monophosphate synthase, a metabolic disease that interferes with pyrimidine biosynthesis, were related to a common ancestor, Skokie Sensation Ned. Predicted Differences of milk, fat, dollars, and protein from the July 1986 sire evaluation on 290 Holstein bulls born between 1975 and 1981 were analyzed for differences in the following groups: 5 heterozygous sons, 7 heterozygous grandsons, 5 normal sons, 20 normal grandsons of Ned, and a random sample of 253 normal bulls unrelated to Ned. From generalized least squares analysis, heterozygotes had higher estimates of genetic merit by 158 kg PD milk, 37 PD dollars, and 4.9 kg PD protein. Although an advantage was observed for heterozygotes within a family, descendants of Ned had lower estimates of genetic merit than their normal contemporaries. Sons of Ned had higher PD protein than grandsons of Ned, regardless of their uridine-5' monophosphate synthase level. Propagation of the reproductively undesirable allele for deficiency of uridine-5'-monophosphate synthase should be controlled. PMID- 1500594 TI - Increased cardiac awareness in panic disorder. AB - We investigated cardiac perception in panic disorder with both self-report and objective measures. In Study 1, 120 patients with panic disorder, 86 infrequent panickers, and 38 patients with other anxiety disorders reported greater cardiac and gastrointestinal awareness than 62 normal control subjects. Subjects with panic attacks reported greater cardiac awareness, but not gastrointestinal awareness, than those with other anxiety disorders. Studies 2 and 3 included a test of heart rate perception in which subjects silently counted their heart beats without taking their pulse. In Study 2, 65 panic disorder patients showed better performance than 50 infrequent panickers, 27 patients with simple phobias, and 46 normal control subjects. No group differences were found in ability to estimate time intervals. In Study 3, 13 patients with panic disorder and 15 with generalized anxiety disorder showed better heart rate perception than 16 depressed patients. PMID- 1500595 TI - Psychological characteristics of dieters and bulimics. AB - Two studies examined the continuum and discontinuity models of the relation between dieting and bulimia nervosa. In Study 1, 21 dieters, 19 bulimics, and 33 nondieting controls were compared on 24 measures. Multivariate analyses revealed that each of the groups differed significantly from the other two. Univariate analyses found 18 significant differences between bulimics and dieters and 1 significant difference between dieters and controls. In Study 2, 86 subjects completed measures of psychological functioning, dieting, and bulimia nervosa. On the basis of regression analyses using factor scores from the psychological variables as predictors, high scores on a psychopathology factor and low scores on a defensiveness factor predicted both bulimia and dieting. Low self-concept scores also predicted bulimia. These data indicate that both continuity and discontinuity characterize the relation between dieting and bulimia. PMID- 1500596 TI - Relations among self-reported depressive symptoms in clinic-referred children versus adolescents. AB - Although there is consensus regarding the existence of childhood depression, disagreement remains as to whether symptoms are developmentally isomorphic. Previous studies focused on developmental differences in symptom levels; analyses of relations among symptoms may be more appropriate, however. Here both approaches were used to compare the Children's Depression Inventory responses from 1,030 clinic-referred children and adolescents. Four of nine symptom categories showed significant developmental differences in their correlations with total score. Externalizing behavior and guilt were more strongly related to depression in children than adolescents; affective symptoms and concerns about the future showed the reverse pattern. Results illustrate the importance of considering relations among symptoms as well as differences in symptom levels when evaluating theoretical claims about developmental differences in the nature of clinical syndromes. PMID- 1500597 TI - Increases in depressive symptomatology in the rural elderly: results from a cross sectional and longitudinal study. AB - Depressive symptomatology was examined in a large sample of noninstitutionalized older adults using the Center for Epidemiological Studies-Depression scale (CES D). Both cross-sectional and longitudinal data showed age-related increases in mean CES-D scores and increases in the percentage of respondents scoring at or above the cutoff score of 16. Variables collected at baseline in the longitudinal study from 2,032 participants 65 years of age and older were significant predictors of depressive symptomatology 3 and 6 years later. Baseline CES-D scores accounted for the largest proportion of the variance. PMID- 1500598 TI - Predictors and consequences of childhood depressive symptoms: a 5-year longitudinal study. AB - A 5-year longitudinal study investigated the interrelationships among children's experiences of depressive symptoms, negative life events, explanatory style, and helplessness behaviors in social and achievement situations. The results revealed that early in childhood, negative events, but not explanatory style, predicted depressive symptoms; later in childhood, a pessimistic explanatory style emerged as a significant predictor of depressive symptoms, alone and in conjunction with negative events. When children suffered periods of depression, their explanatory styles not only deteriorated but remained pessimistic even after their depression subsided, presumably putting them at risk for future episodes of depression. Some children seem repeatedly prone to depressive symptoms over periods of at least 2 years. Depressed children consistently showed helpless behaviors in social and achievement settings. PMID- 1500599 TI - Perceived-competence deficit in anorexia nervosa. AB - Anorexia nervosa patients are portrayed as competent and accomplished and yet they feel ineffective and diffident. The assessment of this aspect of their self esteem presents methodological problems. The Interests and Abilities Questionnaire was designed to measure interests and perceived abilities in typical adolescent activities. The disparity between interests and perceived abilities--perceived-competence deficit (PCD)--was hypothesized to be characteristic of anorexics. Three groups of females, aged 14 to 24, were studied: 13 anorexic inpatients, 13 psychiatric inpatients without an eating disorder but of similar severity of illness, and 48 nonclinical subjects. Similar to the nonclinical controls, anorexics were interested in a variety of activities; similar to control patients, anorexics rated their abilities lower than nonclinical subjects. In PCD, anorexics scored significantly higher than both control groups; this difference was not related to level of depression. PMID- 1500600 TI - Factorial structure of traits delineating personality disorders in clinical and general population samples. AB - Categorical and dimensional models for classifying personality disorders were evaluated by comparing the structure of personality pathology in a clinical sample (n = 158) with the structure in a general population sample (n = 274). Subjects completed 100 personality scales. Separate factor analyses revealed similar structures in the 2 samples. An underlying structure in a combined sample showed limited agreement with the concepts of the Diagnostic and Statistical Manual of Mental Disorders (American Psychiatric Association, 1987). Fifteen factors were retained: Generalized Distress, Rejection, Restricted Expression, Compulsivity, Stimulus Seeking, Insecure Attachment, Diffidence, Intimacy Problems, Oppositionality, Interpersonal Disesteem, Conduct Problems, Cognitive Dysfunction, Affective Reactivity, Narcissism, and Social Apprehensiveness. The results are consistent with a dimensional representation of personality disorder. PMID- 1500601 TI - Stepping through the drug use sequence: longitudinal scalogram analysis of initiation and regular use. AB - Using a new technique for tracing the sequence of use over time, this study examined the pattern of drug involvement among 4,145 West Coast adolescents over the 4-year span from Grades 7-10. During the period covered, the mid- to late 1980s, we found no evidence that cocaine has become a gateway drug. However, the data provided some support for treating cocaine initiation as a separate stage that precedes the onset of hard drugs other than pills. The analysis also showed that increased involvement with legal drugs constitutes an important step in the transition to hard drug use for most adolescents. Weekly alcohol use followed marijuana use and preceded use of all other illicit drugs for Hispanic, White, and Black youth. However, it followed use of hard drugs for Asians. Weekly smoking formed a distinct stage between initial use of pills and other hard drugs for non-Hispanic Whites. The results underscore the importance of prevention efforts aimed at curbing the transition to regular use of alcohol and cigarettes, as well as their initial use. PMID- 1500602 TI - Reaction to trauma: a cognitive processing model. AB - We integrated existing cognitive processing models of posttrauma reactions into a longitudinal model. Data were obtained after a multiple shooting in a city office block. The subject group comprised 158 office workers who were in the building at the time of the shootings. The methodology of this research was a repeated measures survey, with data collection at 4, 8, and 14 months posttrauma. Measures included the Impact of Events Scale (IES) and the Symptom Checklist-90-Revised. A path analysis was performed with the IES as an indication of cognitive processing. Intrusion and avoidance were shown to mediate between exposure to trauma and symptom development. Intrusion was also found to be negatively related to subsequent symptom levels. The findings provide provisional support for a cognitive processing model. PMID- 1500603 TI - Panic attacks in the nonclinical population: an empirical approach to case identification. AB - Although self-reports of panic attacks are common among student populations, it is not clear that their panic experiences are actually comparable to those of patients with clinical anxiety disorders. An empirical approach was taken to this problem by using a cluster analysis procedure to identify subjects within two samples of university students who reported panic attack symptom profiles that resembled those of patients with panic disorder. Such empirically defined "clinical" panic attacks were reported by 7.0% and 8.1% of the two samples. This predominantly female group accounted for most of the increased psychopathology that has been reported in previous studies of nonclinical panic. PMID- 1500604 TI - Proneness to shame, proneness to guilt, and psychopathology. AB - The links between shame and guilt and psychopathology were examined. In 2 studies, 245 and 234 undergraduates completed the Self-Conscious Affect and Attribution Inventory, the Symptom Checklist 90, the Beck Depression Inventory, the State-Trait Anxiety Scale, and the Attributional Style Questionnaire. Results failed to support Lewis's (1971) notion that shame and guilt are differentially related to unique symptom clusters. Shame-proneness was strongly related to psychological maladjustment in general. Guilt-proneness was only moderately related to psychopathology; correlations were ascribable entirely to the shared variance between shame and guilt. Although clearly related to a depressogenic attributional style, shame accounted for substantial variance in depression, above and beyond attributional style. PMID- 1500605 TI - Forms of memory failure in schizophrenia. AB - Effortful and automatic memory task performances were examined in 36 schizophrenic patients and 18 normal control Ss. Tasks included free recall, recognition, and frequency estimation. Patients demonstrated impairment in recall, in recognition, in semantic encoding, and in frequency estimation. Deficits were observed across tasks despite differences in attentional demands. The results suggest a basic compromise of memory function, which is consistent with recent neuroimaging evidence of structural or physiological abnormalities in frontal and temporal lobe structures in schizophrenia. PMID- 1500606 TI - Childhood depression and conduct disorder: I. Behavioral, affective, and cognitive aspects of family problem-solving interactions. AB - We assessed the family interactions of depressed, conduct-disordered, mixed depressed-conduct-disordered, and nonclinic children, ages 7-14 years, during a standardized family problem-solving discussion in the clinic. The child's and the mother's problem-solving proficiency, aversive behavior, and associated affective behavior (depressed and angry-hostile) were observed. The child and mother also rated each other's affect during the interaction for the dimensions sad, angry, critical, and happy on Likert-type scales. The child's and mother's cognitive constructions about the interaction were assessed using video-mediated recall. Although all clinic groups had lower levels of effective problem solving than did nonclinic children, their deficiencies were somewhat different. Mixed and depressed children displayed high levels of depressed affect and low levels of angry affect, whereas conduct-disordered children displayed both angry and depressed affect. In addition, conduct-disordered children had lower levels of positive problem solving and higher levels of aversive content than did non conduct-disordered children. Depressed and conduct-disordered children had higher levels of self-referent negative cognitions than did mixed and comparison children, and depressed children also had higher other-referent negative cognitions than did all other groups. The study provides support for theories and treatment that stress the importance of family problem-solving and conflict resolution skills in child psychopathology. PMID- 1500607 TI - Childhood depression and conduct disorder: II. An analysis of family interaction patterns in the home. AB - Few researchers have assessed family interaction patterns associated with childhood depression, especially using observations in natural settings. We directly sampled the interaction patterns of families with depressed, conduct disordered, mixed depressed-conduct-disordered, and comparison children ages 7-14 years in their homes during the evening meal. Observational measures were taken of positive and aversive behaviors and affect expression for both parents, the referred children, and their siblings. Results replicated previous research showing that conduct-disordered children express high levels of aversive behavior and anger and are part of a family system marked by conflict and aggression. The depressed children were exposed to maternal aversiveness but did not show any evidence of elevated levels of anger or aversiveness in their own behavior. Surprisingly, this was also true for the mixed-disorder children. High levels of depression in both groups of depressed children were associated with low levels of conflict and anger in family members. Overall, siblings showed very similar patterns of behavior, and were exposed to similar patterns of parental behavior, as the referred children. Results are discussed in terms of family models that emphasize the function of aggression and depression in the maintenance of child psychopathology. PMID- 1500608 TI - Longitudinal relationships among pain, sleep problems, and depression in rheumatoid arthritis. AB - This research evaluated the relationship between pain and sleep problems, and the role of pain and sleep problems in depression, in a sample of 242 patients who had been diagnosed with definite or classical rheumatoid arthritis (RA). Patients completed the Pain scale of the Arthritis Impact Measurement Scales, the Center for Epidemiological Studies Depression Scale, and self-reports of sleep disturbance at two data waves over a 2-year interval. Cross-sectional multiple regression analysis revealed that the sleep problems variable was independently associated with depression at Time 1. Longitudinal multiple regression analyses demonstrated that prior pain predicted subsequent adverse changes in sleep problems, whereas sleep problems did not affect pain over time, and prior pain and the interaction of high pain and high sleep problems were independently associated with depression from Time 1 to Time 2. These data suggest that pain may exacerbate sleeping difficulty in RA patients, and that both factors may contribute to depression over time. PMID- 1500609 TI - Reports of real and false memories: the relevance of hypnosis, hypnotizability, and context of memory test. AB - Thirty high- and 30 low-hypnotizable subjects saw slides of a purse snatching and then imagined seeing the slides in hypnosis or waking conditions. The experimenter suggested the offender had a moustache (true), wore a scarf (false), and picked up flowers (false). Memory was tested by the experimenter after the suggestion, by another experimenter during an inquiry session, and again by the 2nd experimenter after the experimenter appeared to end the session. Hypnotizability, but not hypnosis, was associated with false memory reports; more high-than low-hypnotizable subjects reported false memories. The context of testing influenced true and false memory reports; fewer reports occurred in an informal rather than a formal test context. PMID- 1500610 TI - Social factors and the psychobiology of depression: relations between life stress and rapid eye movement sleep latency. AB - We examined psychosocial factors (i.e., life stress) and biological factors (i.e., REM sleep latency) that are hypothesized to be of complementary importance for defining depressive subtypes in a sample of 61 nonpsychotic, endogenous major depressives. Subjects were evaluated on several diagnostic scales for life stress, on electroencephalographic sleep data, and on 2 symptom measures for depression. As predicted, persons with severe stress that occurred shortly before depression onset had essentially normal REM latency values; patients without such stress had reduced REM latency values. Both stress and REM latency were also associated with greater severity of self-reported depressive symptoms. Alternative explanations of these findings are discussed, with particular emphasis on different roles of pre-onset and post-onset stressors. PMID- 1500611 TI - Response to hyperventilation and inhalation of 5.5% carbon dioxide-enriched air across the DSM-III-R anxiety disorders. AB - Anxiety disorder patients (n = 198; under criteria of the Diagnostic and Statistical Manual of Mental Disorders; rev. 3rd ed.; American Psychiatric Association, 1987) and nonanxious control subjects (n = 25) underwent challenges of 90 s of voluntary hyperventilation and 15 min of 5.5% carbon dioxide in air. Panic disorder subjects showed a greater subjective response to both challenges than did subjects with other anxiety disorders, who in turn responded more than did control subjects. Furthermore, subjects with panic disorder as an additional diagnosis tended to report more subjective response than did anxiety disorder subjects without panic disorder. The best prechallenge predictor of response to each procedure was a measure of fear of physical symptoms. The findings support previous results that have pointed to a greater fear or anxiety-inducing effect of these challenge procedures in panic disorder patients, as compared with other subjects. PMID- 1500612 TI - DSM-III-R personality disorders and the five-factor model of personality: an empirical comparison. AB - The relationship between the five-factor model (FFM) of personality and the Diagnostic and Statistical Manual of Mental Disorders (rev. 3rd ed.; DSM-III-R) personality disorders was examined in a sample of 54 psychiatric outpatients. Correlations between raw scores on the NEO-Personality Inventory (NEO-PI) and the number of DSM-III-R personality disorder symptoms rated present using a semistructured interview were computed. In addition, correlations between NEO-PI scores and scores on two self-report personality disorder inventories were also examined to determine which results replicated across instruments. Results indicated that the FFM personality dimensions of Neuroticism, Extraversion, and Agreeableness were most apparent in the DSM-III-R conceptualizations of the personality disorders. PMID- 1500613 TI - Self-criticism in adulthood and recalled childhood experience. AB - We investigated in a sample of 75 medical students the hypothesis that higher levels of self-criticism, a major vulnerability factor for depression, are related to retrospective reports of less satisfactory parenting, even when the potentially confounding factors of mood state and social desirability response set are controlled. At each of 2 measurement times, there were significant cross sectional correlations between parental ratings and both depression and self criticism, but the associations with self-criticism were no longer significant when depression was controlled. However, even after controlling for the effects of mood state and social desirability, persons with high levels of self-criticism at both measurement points (high trait self-criticism subjects) reported significantly worse relationships with their mothers than did the remaining subjects. They were also more likely to report below average relationships with both parents jointly. PMID- 1500614 TI - Confirming the latent structure and base rate of schizotypy: a taxometric analysis. AB - Meehl's (1962, 1990) model of schizotypy and the development of schizophrenia implies that the structure of liability for schizophrenia is dichotomous and that a "schizogene" determines membership in a latent class, or taxon (Meehl & Golden, 1982). The authors sought to determine the latent structure and base rate of schizotypy. They applied Meehl's (1973; Meehl & Golden, 1982) MAXCOV-HITMAX taxometric analytic procedures to a subset of items from the Perceptual Aberration Scale (PAS; Chapman, Chapman, & Raulin, 1978), a prominent psychometric index of schizotypy, derived from a randomly ascertained nonclinical university sample (N = 1,093). The results, in accordance with Meehl's conjectures, strongly suggest that schizotypy, as assessed by the PAS, is taxonic at the latent level with a general population taxon base rate of approximately .10. PMID- 1500615 TI - Clinical depression and implicit memory. AB - We investigated performance on implicit and explicit memory tasks in subjects diagnosed with major depression and matched controls. Depressed subjects showed impaired performance on both the explicit and implicit tasks in comparison with controls. These findings are in contrast to groups such as amnesic patients and older adults, who show preserved abilities on implicit tasks and deficits on explicit tasks. PMID- 1500616 TI - Affective valence and memory in depression: dissociation of recall and fragment completion. AB - Depressed (n = 16) and nondepressed (n = 16) subjects' memory for affectively valenced words was assessed by an explicit test (free recall) and an implicit test (word fragment completion). Under free-recall instructions, depressed subjects recalled significantly more negatively valenced than positively valenced words, whereas the opposite pattern was observed in nondepressed control subjects. These results replicate those previously reported in the literature. The differential effect of word valence was absent, however, when memory was tested implicitly: Depressed and nondepressed subjects exhibited equivalent priming of positive and negative words. These data are discussed in terms of Williams, Watts, MacLeod, and Mathews's (1988) model of depression. PMID- 1500617 TI - Mood-congruent memory in depression: emotional priming or elaboration? AB - We investigated whether mood-congruent memory (MCM) bias in depression is a function of implicit or explicit memory. Implicit memory is taken as a measure of ease of activation, whereas explicit memory also taps elaboration. As expected, MCM bias was found in the explicit memory task but not in the implicit memory task. We believe this finding supports the involvement of elaborative mechanisms in MCM. In addition, memory bias was found with words related to depression but not with words denoting physical threat. Thus, the MCM bias in explicit memory was found to be specific to information that was congruent with depression rather than to all negative information. PMID- 1500618 TI - Depression and implicit memory: a commentary. AB - In this invited commentary, we review four studies in which the issue of whether depression affects priming on implicit memory tests was examined. We conclude that a depressive mood does not affect amount of priming on several implicit memory tests under conditions in which marked effects are shown on conscious recollection (explicit memory). The mood congruity effect (depressives remember depression-related words better than controls; controls remember other types of material better than depressives) also largely disappears on perceptual implicit memory tests. We speculate about reasons for discrepancies in the literature, relate the findings to some current theories of individual differences in memory, and suggest some directions for future research. PMID- 1500619 TI - Nightmare frequency versus nightmare distress: relations to psychopathology and cognitive style. AB - The hypotheses that psychopathology is related to nightmare distress but not nightmare frequency and that cognitive style is related to nightmare frequency were examined. The sample consisted of 85 subjects (58 women and 27 men) who completed several measures: a sleep and dream inventory, Symptom Check List-90-R, Fear Survey Schedule-II, Beck Depression Inventory, an abbreviated version of the Harvard Group Scale of Hypnotic Susceptibility, Vividness of Visual Imagery, an absorption scale, a social desirability scale, and the Boundaries Questionnaire. The results strongly support the first hypothesis but only slightly the second. Such findings underscore the need to differentiate nightmare frequency from suffering (waking distress associated with nightmares) and suggest that although frequency may be related to an intensification of dreaming process, suffering is related to waking emotional adjustment. PMID- 1500620 TI - Regulation of IgE synthesis in humans. PMID- 1500621 TI - Food allergy and the role of immunotherapy. PMID- 1500622 TI - A new radioimmunoassay using a commercially available solid support for the detection of IgE antibodies against muscle relaxants. AB - It is well established that muscle-relaxant drugs may be responsible for anaphylactoid reactions during anesthesia. In this study, we developed an in vitro test with a commercially available solid phase for the detection of specific IgE directed to the tertiary or quaternary ammonium groups of neuromuscular-blocking drugs. The solid-phase complex was P-aminophenylphosphoryl choline (PAPPC) immobilized on agarose, and an RIA was performed with an antihuman IgE labeled with 125I. The results, expressed as the percentage of 125I labeled anti-IgE linked to the solid phase, were at 0.41 +/- 0.19 for 34 control sera from nonallergic healthy adults, with an upper limit estimated at 1%. The values obtained with the sera of 31 allergic patients ranged from 0.6% to 41% with a sensitivity of 97%. The specificity and the positive predictive value of the PAPPC RIA were 97% and 94%, respectively. These results were compared with results of other RIAs with morphine, trimethylamine, triethylamine immobilized on epoxy-activated Sepharose, and choline hydrochloride immobilized on Sepharose (quaternary ammonium Sepharose RIA) and with Phadebas RAST succinylcholine and Phadebas RAST alcuronium. The PAPPC RIA appears to be the most efficient test to screen sera for the presence of IgE antibodies directed to neuromuscular-blocking drugs. One major advantage is that this solid phase is commercially available and ready to use. This advantage will improve the accuracy in the comparison of the results with results from different laboratories. PMID- 1500623 TI - The effect of recombinant human interleukin-5 on eosinophil accumulation and degranulation in human nasal mucosa. AB - Recombinant human interleukin-5 (rhIL-5) was administered repeatedly onto the nasal mucosa of individuals with Japanese cedar pollinosis outside the pollen season. The numbers of eosinophils and epithelial cells and the amount of eosinophil cationic protein (ECP), secretory IgA (S-IgA), and IgA in the nasal lavage fluid increased significantly after the application of rhIL-5. Responsiveness to histamine was also enhanced after the application. When S-IgA was administered onto the nasal mucosa after application of rhIL-5, the amount of ECP in the nasal lavage fluid was significantly more increased. The above findings together with the facts that IL-5 promotes production of IgA, that IgA receptors are present on eosinophils, and that rhIL-5 does not increase release of ECP from eosinophils isolated from the peripheral blood suggest that a series of possible reactions consisting of (1) IL-5--induced production of IgA from the immune-mediating cells, (2) binding of secretory components released from either serous glandular cells or epithelial cells of the nasal mucosa with IgA, (3) release of ECP from eosinophils induced by S-IgA and/or IgA, (4) epithelial damage to the nasal mucosa, and (5) development of nasal hyperreactivity to histamine. PMID- 1500624 TI - In vivo expression of CD69 on lung eosinophils in eosinophilic pneumonia: CD69 as a possible activation marker for eosinophils. AB - The antigen, CD69, has been demonstrated to be expressed on activated T cells and natural killer cells. There have been no studies concerning the expression of CD69 on eosinophils. In this article, we demonstrate that lung eosinophils obtained from the bronchoalveolar lavage fluid of patients with eosinophilic pneumonia expressed significant levels of CD69, whereas peripheral blood (PB) eosinophils did not express CD69. We also activated PB eosinophils in vitro using phorbol myristate acetate and cytokines to determine whether CD69 was expressed. PB eosinophils expressed CD69 after short-term culture with phorbol myristate acetate and eosinophil hemopoietic cytokines (interleukin-3, granulocyte macrophage--colony-stimulating factor, and interleukin-5). These findings suggest that CD69 may be a useful marker for activated eosinophils at inflammatory sites. PMID- 1500625 TI - Imported fire ant immunotherapy: effectiveness of whole body extracts. AB - The purpose of this study was to determine if whole body extract (WBE) immunotherapy for imported fire ant (IFA) hypersensitivity is effective. This evaluation was carried out by retrospectively interviewing 76 patients with a history of generalized allergic reactions to IFA stings and positive skin tests to IFA-WBE. The study groups consisted of 65 patients on immunotherapy and 11 similar patients who were not treated for various reasons. In addition, an IFA sting challenge was performed in 30 volunteers of the 65 patients on immunotherapy. The retrospective review showed that of the 65 patients on immunotherapy there had been 112 subsequent field-sting episodes in 47 patients. Only one sting episode in this group (2.1%) produced an anaphylactic reaction. Six of the 11 patients not on immunotherapy have had subsequent field re-sting episodes, and each has had a systemic reaction. Repeat skin testing on 31 of the 65 patients in the immunotherapy group showed persistent positive responses in five (16%), but each was at a lower dilution than initially. Responses of the other 26 of the 31 patients who had skin testing had become negative. The four untreated patients who were available for skin testing continued to have positive responses at comparable dilutions on skin testing. Sting challenges carried out on 30 volunteers from the 65 patients (all from the 31 who had repeat skin tests) on immunotherapy resulted in only local reactions.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1500626 TI - Serum IgE in nonatopic smokers, nonsmokers, and recent exsmokers: relation to lung function, airway symptoms, and atopic predisposition. AB - The influence of smoking on serum IgE (s-IgE) was studied in a selected nonatopic population. The variation in s-IgE was followed during 1 year of smoking abstinence. The study included 287 smokers and 137 never smokers. IgE was higher in smokers compared with IgE in never smokers (p less than 0.005). Male smokers had higher s-IgE than female smokers (p less than 0.01). S-IgE was independent of age and claims of atopy among first-degree relatives. Weighted pack-years consumption was defined for cigarette smokers by modifying pack-years consumption by nicotine content of the brand smoked. Weighted pack-years consumption was associated with level of s-IgE (p less than 0.05). S-IgE was higher in smokers with airway symptoms compared with that in smokers without symptoms (p less than 0.01). In smokers older than 50 years of age, there tended to be decreased FEV1 residuals (0.05 less than p less than 0.06), and presence of airway symptoms was (p less than 0.03) associated with high levels of s-IgE independent of each other. In 92 quitters, s-IgE increased during the first 26 weeks of abstinence (p less than 0.05), and after 1 year, s-IgE had returned to baseline. The increase was only observed in smokers younger than 40 years and had no relation to variations in FEV1 during the 1-year follow-up. The increase in s-IgE after smoking cessation was transient, of minor clinical importance, and probably caused by a relief from an immunosuppressive influence. PMID- 1500627 TI - Characterization of latex antigens and allergens in surgical gloves and natural rubber by immunoelectrophoretic methods. AB - Allergy to natural rubber (latex) products is increasingly frequent among both medical personnel and lay subjects. Although individual antigens and allergens in latex products have not been fully characterized, they are believed to derive from the sap of the rubber tree. Rabbit IgG and human IgE antibodies against rubber proteins were used to characterize antigens and allergens in surgical latex gloves and natural rubber by crossed immunoelectrophoresis and its modifications. The results from crossed-line immunoelectrophoresis demonstrated that the surgical latex gloves had at least 10 antigens in common with natural rubber sap and ammoniated latex. In crossed radioimmunoelectrophoresis, at least six of the 10 protein antigens in the surgical glove extract and natural rubber were allergens since they bound IgE antibodies from the latex-allergic patients' sera. The surgical glove extract also demonstrated one allergen not found in natural rubber, suggesting that rubber proteins may be altered during glove manufacture. PMID- 1500628 TI - Effect of environmental factors on the development of allergic disorders in infancy. AB - A total of 1167 infants were followed for 1 year in a population-based prospective study to assess the effect of environmental factors on the development of allergic disorders. Some of these environmental factors are interdependent. Mothers who formula fed their infants smoked more often (p less than 0.001) and tended to belong to lower social classes (p less than 0.01). Logistic regression analysis was performed to adjust for these confounding variables. Maternal smoking adversely affected the prevalence of asthma (p = 0.003) defined as three or more separate episodes of wheezing and total allergy (p = 0.02). Infants in lower socioeconomic groups developed asthma significantly more often (p = 0.03) than infants born in higher socioeconomic groups. There was a nonsignificant trend for infants born in summer to develop asthma more than infants born in winter (p = 0.08). No effect of these factors was observed on eczema, food intolerance, or on the subgroup of infants with definite allergy (clinical disorder with positive skin prick test [SPT]). Exposure to animal dander did not influence the prevalence of clinical disorder, but positive SPT reaction to cat dander was more prevalent in infants who were exposed to cats and/or dogs (p = 0.04). Positive SPT to house dust mite occurred significantly more often in infants who were formula fed (p = 0.05). The environmental factors had a profound effect on the prevalence of asthma but not on other allergic disorders. PMID- 1500629 TI - Nasal beclomethasone prevents the seasonal increase in bronchial responsiveness in patients with allergic rhinitis and asthma. AB - Experimental studies have demonstrated that induction of a nasal allergic reaction can lead to an increase in bronchial responsiveness (BR). To assess the clinical relevance of these experimental changes to chronic asthma, we sought to determine the effect of nasal beclomethasone dipropionate (Bdp) on BR in patients with seasonal allergic rhinitis and asthma. Eighteen subjects with histories of seasonal allergic rhinitis and asthma during the fall pollen season with positive skin tests to short ragweed and bronchial hyperresponsiveness to inhaled methacholine were assigned to receive either nasal Bdp (336 micrograms/day) or placebo for the entire ragweed season. Patients recorded daily nasal and chest symptoms, nasal blockage index, oral peak expiratory flow rates, and supplemental medication use. BR to methacholine was measured during the baseline period and 6 weeks into the ragweed season. Although the Bdp group did have a significant improvement in nasal blockage index, there was no improvement in daily asthma symptom scores, oral peak expiratory flow, or asthma medication use. However, subjects treated with Bdp were protected from the increase in BR seen in the placebo group (geometric mean PC20 placebo group: baseline = 0.70, week 6 = 0.29; Bdp group: baseline = 0.80, week 6 = 0.93; intergroup difference, p = 0.022). We conclude that nasal corticosteroid therapy can prevent the increase in BR associated with seasonal pollen exposure in patients with allergic rhinitis and asthma. PMID- 1500630 TI - Treatment of peanut allergy with rush immunotherapy. AB - Peanut and peanut products are a common food in the diet. Peanuts are also one of the most common foods responsible for food-induced anaphylaxis. Patients rarely lose sensitivity to peanuts. Although the ideal treatment is avoidance, this is often not possible because of hidden exposures; therefore, a more effective treatment is needed. Subjects with confirmed peanut allergy were treated in a double-blind, placebo-controlled study with peanut immunotherapy or placebo. Objective measures of efficacy included changes in symptom score during double blind placebo-controlled peanut challenge (DBPCPC) and titrated end point prick skin tests (PST). Three subjects treated with peanut immunotherapy completed the study. These subjects displayed a 67% to 100% decrease in symptoms induced by DBPCPC. Subjects also had a 2- to 5-log reduction in end point PST reactivity to peanut extract. One placebo-treated subject completed the study. This subject had essentially no change in DBPCPC symptom scores or PST sensitivity to peanut. Two other placebo-treated subjects underwent a second PST session. These subjects had a 1- to 2-log increase in skin test sensitivity to peanut. All peanut-treated subjects were able to reach maintenance dose, and in no case did an anaphylactic reaction occur secondary to the peanut immunotherapy. The current study provides preliminary data demonstrating the efficacy of injection therapy with peanut extract and provides a future line of clinical investigation for the treatment of this potentially lethal disease. It should be noted, however, that the rate of systemic reactions with rush immunotherapy was 13.3%.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1500631 TI - The use of in vitro tests for IgE antibody in the specific diagnosis of IgE mediated disorders and in the formulation of allergen immunotherapy. American Academy of Allergy and Immunology. PMID- 1500633 TI - Occupational asthma induced by a carpet fungicide--tributyl tin oxide. PMID- 1500632 TI - Prophylaxis of AIDS-related Pneumocystis carinii pneumonia with aerosolized pentamidine in a patient with hypersensitivity to systemic pentamidine. PMID- 1500634 TI - Fetal dexamethasone exposure accelerates development of renal function: relationship to dose, cell differentiation and growth inhibition. AB - Fetal exposure to high doses of glucocorticoids slows cellular development and impairs organ performance, in association with growth retardation. Nevertheless, low doses of glucocorticoids may enhance cell differentiation and accelerate specific functions. The current study examined this apparent paradox in the developing rat kidney, using doses of dexamethasone that span the threshold for growth impairment: 0.05 or 0.2 mg/kg given on gestational days 17, 18 and 19. At the lower dose, which did not significantly retard body growth, the postnatal development of tubular reabsorptive capabilities for sodium, potassium, osmotic particles, water and urea was accelerated. These effects were less notable at the higher dose, which caused initial body growth impairment. The selectivity toward promotion of tubular function was evidenced by the absence of effect of either dose of dexamethasone on development of glomerular filtration rate. Because of the wide spectrum of dexamethasone's effects on tubular function, we also assessed fetal kidney adenylate cyclase as a means of detecting altered cell differentiation in the prenatal period during which dexamethasone was given. Either glucocorticoid dose increased the total adenylate cyclase catalytic activity (assessed with forskolin). Thus, the net effect of fetal dexamethasone exposure on development of renal excretory capabilities probably represents the summation of promoted cell differentiation and slowed development consequent to growth retardation. At low dose levels, the former effect predominates, leading to enhanced functional development, whereas higher doses that interfere with general growth and development can offset the direct promotional effect. PMID- 1500635 TI - Prostaglandin production in the umbilical and uterine circulations in pregnant sheep at 129-136 days gestation. AB - Prostaglandins circulating in the maternal and foetal blood have been implicated in important physiological systems. These functions include foetal adrenal function, maintenance of patency of the ductus arteriosus, regulation of uterine and umbilical circulations, and labor and delivery type myometrial contractions. The placenta is a major site of prostaglandin production in pregnancy. Limited data are available which combine measurements of veno-arterial differences across the uterine and umbilical circulations with blood flow in these circulations to enable calculation of umbilical-placental and utero-placental production rates for the prostaglandins. In chronically instrumented pregnant ewes, between 129 and 136 days of gestation, prostaglandin F2 alpha(PGF2 alpha), 13, 14 dihydro-15 keto prostaglandin F2 alpha (PGFM), prostaglandin E2 (PGE2) were measured in the maternal carotid artery and uterine vein. Foetal PGE2, and 6-keto-prostaglandin F1 alpha (6-keto-PGF1 alpha) (the major metabolite of prostacyclin) were measured in umbilical venous and foetal descending aorta arterial plasma. Umbilical and uterine blood flow were measured using the diffusion-equilibrium technique. Uterine blood flow was 1693 +/- 137 ml.min-1 (mean +/- SEM); uterine production rates were 480 +/- 88 ng.min-1 for PGF2 alpha, 517 +/- 144 ng.min-1 for PGFM, and 165 +/- 27 ng.min-1 for PGE2. Umbilical blood flow was 147 +/- 17 ml.min-1.kg-1 foetal body weight. Umbilical production rates into the foetal circulation were 11 +/- 2 ng.min-1.kg-1 for PGE2 and 6 +/- 2 ng. ng.min-1.kg-1 foetal body weight for PGI2. PMID- 1500636 TI - Foetal circulatory responses to arrest of uterine blood flow in sheep: effects of chemical sympathectomy. AB - Acute foetal asphyxia, caused by arrest of uterine blood flow, increases both sympathetic activity and peripheral vascular resistance and decreases blood flow to peripheral organs (Jensen et al., J. Dev. Physiol., 9, 543-559). The rapidity and uniformity of this peripheral vasoconstriction suggest that the sympatho neuronal system may reflexly cause these initial blood flow changes during acute asphyxia. To test this hypothesis, we studied 5 intact and 6 chemically sympathectomized (6-hydroxy-dopamine, 46.1 +/- 6 mg/kg foetal weight) chronically prepared normoxaemic foetal sheep in utero at 0.9 of gestation. Organ blood flows (microsphere method), plasma concentrations of catecholamines, vasopressin, and angiotensin II, acid-base balance and blood gases were measured before, during and after arrest of uterine blood flow for 2 min, i.e., at 0, 1, 2, 3, 4 & 30 min. In intact foetuses there was a progressive increase in arterial blood pressure and a rapid circulatory centralization in favour of the brain stem and heart and at the expense of most of the peripheral organs. The changes in peripheral blood flow during and after asphyxia were well reflected by those in the skin and scalp. In chemically sympathectomized foetuses, arterial blood pressure fell transiently at 1 min of asphyxia and cardiac output was redistributed towards the carcass and intestinal organs at the expense of the heart, spinal medulla, and placenta. We conclude that in foetal sheep at 0.9 of gestation, the short-term adaptation to arrest of uterine blood flow is a rapid and profound peripheral vasoconstriction to effect an increase in arterial blood pressure. This initial response during circulatory centralization, which is necessary to increase or maintain blood flow to the heart, brain stem, and placenta, is blunted by sympathectomy. Thus, the foetal sympatho-neuronal system is important for short-term adaptation to and intact survival of asphyxia. PMID- 1500637 TI - A modified helium dilution technique for measuring small lung gas volumes. AB - The present study was undertaken to devise an accurate method for measuring functional residual capacity, FRC, in small and lively newborn animals such as lambs and piglets under flexible laboratory conditions using relatively simple equipment. This was achieved by adapting the standard helium dilution method so that FRC could be calculated from the helium equilibration concentration reached when the subject, having breathed a gas mixture with a high helium concentration, rebreathed from an air-filled spirometer. Using this technique, typical results for test volumes of 10, 20, 30 and 40 ml were measured as 10.7 +/- 0.34, 20.2 +/- 0.19, 30.5 +/- 0.40 and 40.6 +/- 0.75 ml respectively with corresponding coefficients of variation of 6.4%, 1.9%, 2.6% and 3.7%. Repeat measurements made on each of 3 urethane anaesthetised rabbits gave values for FRC of 45.64 +/- 0.9 ml (5 measurements), 37.22 +/- 0.8 ml (8 measurements) and 48.95 +/- 0.99 ml (8 measurements) confirming the reproducibility of results from animal preparations. The FRC of newborn lambs (12 animals) was 81.4 +/- 9.2 ml. The technique also allowed clear recordings of respiratory pattern essential to the analysis of variations in FRC. PMID- 1500638 TI - Ion transport regulation of lung liquid secretion in foetal lambs. AB - To test the hypothesis that liquid formation in the foetal lung reflects the balance between Cl- secretion and Na+ absorption by the respiratory tract epithelium, we studied the independent and combined effects of selective ion transport inhibitors on basal production of lung liquid in foetal lambs. We prepared 19 foetal lambs (gestation 125 +/- 4, term = 147 days) with chronic indwelling catheters for subsequent measurement of luminal liquid production over time (JV). Using an impermeant tracer technique, we measured JV before and after tracheal instillation of 2 different inhibitors of ion transport: bumetanide, a Na(+)-K(+)-2Cl- co-transport inhibitor, and amiloride, a Na+ transport inhibitor. In 7 foetuses we sequentially added bumetanide (10(-4) M) and 2 different concentrations of amiloride (10(-6) M, 10(-4) M) to the liquid within the lung lumen. After we gave bumetanide, JV decreased from 12 +/- 4 ml/h to 0 +/- 5 ml/h and subsequently increased during the 2 periods of amiloride exposure (10(-6) M: 6 +/- 5 ml/h; 10(-4) M: 7 +/- 7 ml/h). In 5 control studies we gave bumetanide, followed by only amiloride vehicle. JV for all time periods in the control studies was similar to the experimental group, demonstrating no effect of amiloride. In 5 foetuses we administered the 2 concentrations of amiloride before bumetanide. There was no change in JV with either concentration of amiloride (baseline: 13 +/- 2 ml/h; 10(-6) M amiloride: 15 +/- 5 ml/h; 10(-4) M amiloride: 13 +/- 6 ml/h).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1500639 TI - Campylobacter jejuni bacteraemia in children with diarrhoea in Bangladesh: report of six cases. AB - Campylobacter jejuni was isolated from blood cultures from 6 of 6,275 diarrhoeal children seeking treatment at the Clinical Research Centre of the International Centre for Diarrhoeal Disease Research, Bangladesh (ICDDR,B) between April 1989 and December 1990. The clinical records of these 6 children were reviewed. All children were male; 5 were less than 1-year old and were severely malnourished. Five patients presented with watery diarrhoea and one with bloody diarrhoea. Two children died in the hospital. All strains of Campylobacter isolated from the 6 children were negative for cell invasive properties as tested by the Sereny test. Of the two strains tested for serum bactericidal activity, one strain was serum sensitive (growth inhibition), and the other resistant. The ability of C. jejuni to cause bacteraemia suggests that the organisms may be responsible for diarrhoeal diseases especially in young and malnourished children. An early attempt to detect Campylobacter and start effective antimicrobial therapy is indicated. PMID- 1500640 TI - Evaluation of three tissue culture assay systems for the detection of enterotoxins produced by Salmonellae. PMID- 1500641 TI - Bibliography on diarrhoeal diseases. PMID- 1500642 TI - Building and strengthening research capacity in health: the challenge to Africa. PMID- 1500643 TI - Cholera epidemics in Bangladesh: 1985-1991. AB - In 1991, a major epidemic of diarrhoea broke out in Bangladesh. To estimate the extent of cholera during diarrhoea epidemics and to focus on the public health issues related to cholera in Bangladesh, we have used the government figures of the 1991 epidemic and data from our own experience of epidemic interventions in nearly 400 rural upazilas (sub-district) between 1985 and 1989 and in 1991. Our data showed that V. cholerae 01 was the most frequently (40%) isolated enteropathogen during the epidemics. The disease is widely distributed in the country. Only 24% of the total 1,648 laboratory confirmed cholera patients were below 5 years of age, and children below 2 years of age accounted for only 10% of the total. Access difficulty to medical care and absence of a reliable surveillance were thought to be the constraints to early detection and appropriate intervention, thus, there were more deaths during the epidemics. We have shown that a high proportion (59%) of cholera patients during their illness in the rural areas were not visited by the government surveillance staff and that most (80%) were treated at home. Access to treatment by qualified physicians was limited to 23% of the patients, whereas a large proportion of the patients were treated by the unqualified rural practitioners (68%), and the others (9%) had no access to any health care providers. Our experience also indicated a higher case fatality ratio (14%) prior to intervention by qualified physicians during epidemics and an overall fatality ratio of 4%, despite the significant reduction (less than 1%) achieved by the intervention. Cholera is highly epidemic in Bangladesh.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1500644 TI - Colonisation with digoxin-reducing strains of Eubacterium lentum and Clostridium difficile infection in nursing home patients. AB - Stool specimens obtained from 77 residents of a nursing home were analysed to determine the relationship between colonisation with digoxin-reducing strains of Eubacterium lentum and infection with Clostridium difficile. Patients were categorised according to previous antibiotic treatment, prescription of enteral feedings, and pattern of bowel habits. Colonisation with digoxin-reducing E. lentum was less common in subjects infected with C. difficile, in those treated with antibiotics previously, and in those prescribed enteral feedings. Normal bowel habits were more common in those without C. difficile. The lowest incidence of diarrhoea was seen in patients without C. difficile who were colonised with digoxin-reducing species. This study establishes an inverse relationship between the presence of C. difficile and E. lentum that reduce digoxin which is related to previous treatment with antibiotics and prescription of enteral feedings. Bacterial markers may prove to be a useful tool for predicting clinical disturbances in bowel function. PMID- 1500645 TI - Conjugal transferability of multiple antibiotic resistance in three genera of Enterobacteriaceae in Nigeria. AB - Ninety-eight enteric bacteria were isolated from stool samples of 3,000 diarrhoeal patients during 1988-1989 in Ibadan, Nigeria. The isolates were: 20 Salmonella, 28 Shigella and 50 Escherichia coli. S. typhi and S. Flexneri were most prevalent while serotypes 055, 026 and 0128 were most common among the E. coli. Eight resistance patterns to ampicillin (Ap), streptomycin (Sm), tetracycline (Tc) and chloramphenicol (Cm), the four commonly used drugs in this environment were observed in the isolates. Resistance to all four drugs was common in the Shigella isolates. Conjugation experiments showed that 92% of the isolates tested were able to transfer all or part of their resistance to the recipient E. coli. The Salmonella and Shigella isolates were more efficient in this respect as all the isolates tested (100%) transferred all or part of their resistance character. Ability of the latter two genera to transfer the Ap, Sm, Tc, Cm complete linkage might be enhanced by using more efficient recipient or by mobilisation. Control of antibiotic usage and improvement of personal hygiene were recommended to prevent the spread of drug resistance among the enteric pathogens. PMID- 1500646 TI - Deciding on access and levels of care: a comparison of Canada, Britain, Germany, and the United States. AB - Americans view universal coverage as a reality only if a minimum benefit package is explicitly defined, and discussions about expanding access take place under the slogan of minimum benefits. The policy environment is different in Canada, Britain, and Germany. There, health care costs are controlled and benefits provided under universal coverage plans. Yet the medical services provided in these countries result not from difficult decisions about rationing care at a "minimum" benefit level but from difficult political decisions about the structure of the health care system. Institutional factors rather than explicit policy influence the implicit health priorities in these countries. The United States, in contrast, develops policies that explicitly designate a minimum level of benefits. PMID- 1500647 TI - Privatization in health and human services: a critique. AB - Privatization currently enjoys wide appeal as a solution to public problems. Supporters of privatization hope that shifting responsibility for the funding, administration, and delivery of services to private organizations and individuals will spur market competition and thus lower costs, improve service effectiveness, and enhance program quality. An increasingly common form of privatization in health and human services is contracting with nonprofit organizations. Such contracting, in practice, does not follow market principles but is, instead, fraught with politics and inadequate information and built on long-term relationships between government and contract agencies. The operations and practices of contracting have important implications for the ongoing debate on the desirability of vouchers for health care insurance and for reform in the contracting process. PMID- 1500648 TI - The subsidy provided under Medicare to current enrollees. AB - Contributions made by or for current enrollees to Medicare will cover less than a third of the costs of their expected lifetime benefits, on average. This subsidy is of concern for two reasons. First, because the subsidy is provided regardless of income, some transfers are effectively made to Medicare enrollees from needier groups in the non-Medicare population. Second, as the ratio of Medicare beneficiaries to the working-age population increases in future years, the current generosity of the program may be difficult to maintain. PMID- 1500649 TI - Recording priorities, not Medicare. PMID- 1500650 TI - Another form of "elderly bashing". PMID- 1500651 TI - Medicaid and access to child health care in Chicago. AB - In this article we examine how increasing the reimbursement of physicians and expanding Medicaid eligibility affect access to care for children in Cook County, Illinois, which overlies Chicago. Using Medicaid claims and other data at the zip code level, we compare the places where Medicaid children live with the places where all the physicians who treat children and those who accept Medicaid patients have their practices. Our findings suggest that the recent changes in legislation are unlikely to benefit extremely poor children, who are more likely to live in depressed inner-city areas, where there are few physicians. "Near poor" children whose homes are dispersed throughout the county, who are now eligible for Medicaid as a result of the recent changes, are likely to see improvements in their access to care. Further changes in policy, aimed at enhancing the capacity of institutions providing care, could improve access for the children of the inner city. PMID- 1500652 TI - A blip on the radar screen: formulation and implementation of the Medical Waste Tracking Act. AB - We use the passage and implementation of the Medical Waste Tracking Act of 1988 (MWTA) to explore the implications of health and environmental policies that are formulated in the context of events defined politically as a crisis. Building on Kingdon's (1984) "garbage can" model of policy initiation, we assess the linkage between a policy environment that provides strong but short-lived support for the enactment of a policy and its subsequent implementation. Among the implications of the less-than-impressive substantive results of the MWTA is the lesson that while a crisis can tilt the political balance in favor of regulatory legislation, it cannot as readily produce the consensus required to sustain that regulation at the levels promised in the legislation. PMID- 1500653 TI - Philip Morris's failed experiment in Pittsburgh. AB - The campaign for passage and implementation of Pittsburgh's Smoking Control Ordinance in 1987 illustrates the role controversy plays in tobacco control. Proponents of the ordinance sought at first to keep it noncontroversial, while the tobacco industry tried to defeat the ordinance by generating controversy, claiming that severe economic and social disruption would occur. After the ordinance had been in force for a year, Philip Morris tried to take over its implementation, seeking to redefine the central issue as one of social accommodation rather than health. To succeed, Philip Morris's effort had to be widely accepted and noncontroversial. Proponents of the ordinance countered with controversy to undermine the campaign and expose the company's intentions. The controversy made the established health organizations uncomfortable, causing them to play only a marginal role. Surprisingly, the people who prevailed were the nonsmokers' rights activists, a small group with limited resources. PMID- 1500654 TI - Health policy on the high wire: thirteen days with a presidential campaign. PMID- 1500655 TI - Medical care and the state. Essay review. PMID- 1500656 TI - Factors influencing first relapse in patients with Crohn's disease. AB - To determine whether information available at time of diagnosis of Crohn's disease can predict initial clinical course, I followed 239 patients prospectively from time of diagnosis to initial relapse. The patient's sex, smoking habits, contraceptive usage, disease extent, and presence of granulomas in the first histological specimen were recorded. No association was found between this demographic data and the interval between onset of symptoms and diagnosis, the severity of symptoms at presentation, or the time to relapse. The type of relapse, however, was influenced by the type of the first attack; 70% of relapses were of the same type as the initial attack. Cigarette smoking was associated with ileocolitis (p = 0.028). There was a trend for oral contraceptive users to have ileocolitis, whereas the presence of granulomas in the first histological specimen was not associated with a specific disease distribution. Patients with ileocolitis had more inflammatory attacks than those with ileitis or colitis (p = 0.001). There was also a trend for cigarette smokers and those on oral contraceptives to have more inflammatory attacks, but the presence of granulomas had no effect on the type of relapse. There is little to assist in prognosis of early disease when the diagnosis of Crohn's disease is first made, although the types of attacks tend to repeat themselves. PMID- 1500657 TI - Achalasia: new thoughts on an old disease. AB - Achalasia is the most recognized esophageal motor disorder first described 300 years ago by Sir Thomas Willis. Although the cause of achalasia remains unknown, the disease is thought to occur as a result of degeneration of Auerbach's plexus in the intramural nervous network. A review of the literature reveals that there is reversibility of this disease in some patients after treatment, raising intriguing questions as to the pathogenesis of this disorder and underscoring the need for further study. PMID- 1500658 TI - Uninhibited anal sphincter relaxation syndrome. A new syndrome with report of four cases. AB - I report a new syndrome, in four patients, all male. Patients ranged from 36 to 43 years of age. The main complaint was fecal urgency with occasional fecal soiling. Physical examination as well as pressure and EMG studies of anal sphincters and levator ani muscle were all normal. The only positive finding was an abnormal rectoinhibitory reflex. The external anal sphincter did not contract either reflexively or voluntarily on rectal distension, leaving the relaxing internal sphincter unprotected and uncontrolled. The patients could not oppose the urge to defecate if conditions are inopportune, with resulting urgency and occasional fecal soiling. The cause is unknown, but biofeedback effected improvement in all four cases. PMID- 1500659 TI - Does a risk questionnaire add anything to a colorectal screening project? Report of a 3-year screening experience. AB - A questionnaire to detect persons at high risk for colorectal cancer was used in conjunction with fecal occult blood tests in a 3-year screening program in Northern Israel. Screening was offered to 2,590 persons over 40 years of age and accepted by 1,797 (compliance of 69.4%). In the subsequent 2 years, occult blood testing (Hemoccult II) was offered to those who had had negative tests (compliance rate of 99.6% and 100%). Six hundred and thirty persons (35.1%) had risk factors according to the questionnaire, and 195 of them underwent colonoscopy, with a predictive value of 15.9% for a neoplastic lesion. The Hemoccult II test was positive in 71 participants (4.0%) of whom 67 were investigated with a similar predictive value for neoplastic lesion (16.4%). In the second and third annual screening, the fecal occult blood test was positive in 29 (2.6%) and 27 (2.5%), and had a two and three times higher predictive value for neoplastic lesions, respectively. This was accompanied by a decrease in the cost of discovery. In all three stages, an adenomatous polyp was found in 48, and cancer in 10 participants (2.6% and 0.5% of the 1,797 original participants). Although a questionnaire may be fruitful in colorectal cancer screening, the higher number of participants subjected to further examinations makes this approach very expensive. The annual stool examination for occult blood has a higher predictive value for colonic neoplasm and a lower cost than a one stage, broader population based, study. PMID- 1500660 TI - Calcium and acid rebound: a reappraisal. AB - We review acid rebound, the seemingly paradoxical increase in acid secretion resulting from administration of an antacid. Primarily a laboratory observation, the demonstration of the phenomenon was a major contributing factor to the swift, and possibly unjustified, fall from grace of calcium carbonate in the therapy of peptic ulcer disease despite years of apparently successful use. Calcium, as carbonate or other salts, causes an increase in gastric acid secretion owing, at least in part, to direct ionic stimulation. Another possible mode of action involves antral alkalinization with subsequent gastrin release. Other antacids, notably magnesium hydroxide and aluminum hydroxide, may therefore also cause rebound, but the data in this area are less convincing. Despite the demonstration that acid rebound occurs, no one has thoroughly investigated its clinical import. What limited data actually exist suggest no obvious clinically significant deleterious effect from use of calcium carbonate in peptic ulcer. Because of calcium carbonate's excellent acid-neutralizing capacity, its venerable past record in treating ulcer disease, and recent observations that low-dose antacids heal peptic ulcers, it is appropriate to reevaluate acid rebound, to focus on its clinical significance, if any. PMID- 1500661 TI - Collagenous enterocolitis: a manifestation of gluten-sensitive enteropathy. AB - We report coexistent collagenous colitis and collagenous sprue in a 62-year-old woman with diarrhea. Investigations suggested malabsorption, and small intestinal biopsies demonstrated a flattened mucosa with subepithelial collagen deposition. Colonic biopsies also showed a thickened subepithelial collagen band as well as a striking lamina propria inflammatory cell infiltrate. Symptomatic remission was induced with a gluten/lactose-free diet, oral prednisone, and sulfasalazine and has been maintained with gluten restriction alone. Repeat biopsies after 2 months demonstrated restoration of normal small intestinal and colonic collagen bands; only a chronic inflammatory cell infiltrate (consistent with microscopic/lymphocytic colitis) persisted in colonic biopsies. We propose that, in this instance, collagenous enterocolitis represented a diffuse manifestation of gluten sensitivity. PMID- 1500662 TI - Heterotopic pancreas diagnosed by endoscopic ultrasonography and endoscopic injection of ethanol to make a histologic diagnosis. AB - A gastric submucosal tumor in a 56-year-old man was presumed to be heterotopic pancreas on the basis of endoscopy and endoscopic ultrasonography. To obtain a histologic diagnosis we injected ethanol at the tumor site to create an artificial ulcer. This facilitated the removal of endoscopic biopsy specimens from the submucosal layer so that histologic examination could confirm the presence of heterotopic pancreatic tissue. PMID- 1500663 TI - Endoscopic removal of colonic leiomyoma. AB - Most gastrointestinal leiomyomas are found in the stomach, only 3% of them arising in the colon. Surgical resection of the leiomyoma is usually necessary owing to its submucosal location. We describe a patient with a 1.5 cm pedunculated leiomyoma of the colon successfully removed by colonoscopic snare electrocauterization. We believe this to be the first report of a colonic leiomyoma of this size removed endoscopically without complication. We review the literature regarding gastrointestinal leiomyomas with special attention to pedunculated leiomyomas and their endoscopic management. PMID- 1500664 TI - Pathogenesis of hepatic fibrosis and the role of cytokines. AB - No definitive therapy exists for the treatment of hepatic fibrosis and cirrhosis. Recent evidence suggests that hepatic lipocytes (Ito cells, fat storage cells, or stellate cells of the liver) are responsible for much of the collagen hypersecretion and nodule formation that occurs during hepatic fibrosis and cirrhosis. This review describes the cellular mechanisms of hepatic fibrogenesis emphasizing new experimental data about cytokines or growth factors to suggest potential avenues of future therapeutic design. PMID- 1500665 TI - Epidemiological study of peptic ulcer disease among Japanese and Koreans in Japan. AB - Peptic ulcer among Japanese and Koreans in Japan has rarely been studied. In this 10-year study of hospital-based endoscopy, we focused on the epidemiology of peptic ulcer among these ethnic groups in Japan. Between 1980 and 1990, 81.2% of all patients examined via endoscopy at Saikyo Hospital in Kyoto completed a life style questionnaire: 1,264 Japanese (70.5%), 503 Koreans (28.1%), and 25 persons of unknown ethnicity (1.4%). Characteristics of ulcer disease were almost identical for Koreans and Japanese. Like other world-wide patterns, the male to female ratio was 2.3:1. Unlike results from Western countries, however, the overall gastric ulcer rate was 1.5 times higher than for duodenal ulcer. This higher rate was due to the relatively high rate of gastric ulcer in the older age groups; among persons less than 40 years of age, duodenal ulcer was diagnosed more often than gastric ulcer. The mean age at diagnosis of duodenal ulcer (40.7 years) was significantly lower (p less than 0.005) than that for gastric ulcer (53.7 years). Multivariate-adjusted odds ratios were calculated using a multiple logistic regression model. Cigarette smoking significantly increased the risk for both gastric ulcer (odds ratio = 3.10, 95% confidence interval [CI] 2.1-4.6) and duodenal ulcer (odds ratio = 1.9, 95% CI 1.2-2.9). Age greater than or equal to 40 years (odds ratio = 2.3, 95% CI 1.6-3.3) and consumption of salty foods (odds ratio = 1.5, 95% CI 1.0-2.1) also significantly increased the risk for gastric ulcer.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1500666 TI - Spontaneous nonfistulous barium reflux into the biliary tract: association with duodenal ulcer disease. A report of four cases. AB - Reflux of barium into the bile duct system during a barium study of the upper gastrointestinal tract is rare in the absence of spontaneous or postoperative fistula. We report four patients, three men and one woman, who had such reflux, associated with active duodenal ulcer disease, shown at radiologic and endoscopic investigation. Reflux of gastrointestinal contents into the biliary tract can result from peptic ulcer disease with duodenal involvement. The finding does not necessarily imply fistulous communication, ulcer perforation, or surgical emergency. PMID- 1500667 TI - Adenocarcinoma of unknown origin in a patient with primary intestinal lymphangiectasia. PMID- 1500668 TI - Does endoscopy improve prediction of the prognosis in upper gastrointestinal bleeding? AB - To evaluate the prognostic value of the endoscopic examination, we included 189 consecutive patients with upper gastrointestinal bleeding, in a prospective study. Rebleeding was more frequent in patients with endoscopic stigmata of hemorrhage. The prognostic prediction given by the physician was slightly, but not significantly, improved after the result of the endoscopy was available. However, when the clinical data were evaluated by computer, using the Bayes' theorem, the endoscopic findings provided no additional prognostic value. We conclude that the endoscopic findings have intrinsic prognostic value, but add little to clinical data obtained on admission. PMID- 1500669 TI - Coexistence of Addison's disease, ulcerative colitis, hypothyroidism and pernicious anemia. PMID- 1500670 TI - Pancreatic calcifications in a patient with systemic mastocytosis. PMID- 1500671 TI - Glomerulonephritis associated with acute HAV infection. PMID- 1500672 TI - Endoscopic ultrasonography of benign esophageal cyst simulating leiomyoma. PMID- 1500673 TI - Esophageal intramural pseudodiverticulosis. PMID- 1500674 TI - Spontaneous bacterial peritonitis. PMID- 1500675 TI - Quantitative EEG analysis and evoked potentials to measure (latent) hepatic encephalopathy. PMID- 1500676 TI - Large-volume paracentesis and volume re-expansion: can synthetic plasma expanders safely replace albumin? PMID- 1500677 TI - Nitric oxide production by monocytes in alcoholic liver disease. AB - Nitric oxide, initially described as an endothelial-derived relaxing factor, has recently been recognised as a mediator of macrophage function. We have studied the production of nitric oxide by peripheral blood monocytes from both normal volunteers and alcoholics. This was measured indirectly by assessing nitrite formation. Normal monocytes were found to produce a basal level of nitrite, which could be stimulated more than 6-fold using endotoxin. This effect was abrogated by the addition of nitric oxide synthesis inhibitor, L-n-monomethyl-arginine. A striking difference was observed in the monocytes obtained from alcoholics with and without evidence of alcoholic hepatitis. Whereas the latter behaved in a similar manner to the controls, the former had markedly increased basal levels. In the hepatitis group there was also substantial inhibition of production by L-n monomethyl-arginine. We believe that these results indicate that nitric oxide derived from monocytes may play a role in the pathogenesis of alcoholic liver disease, especially alcoholic hepatitis. PMID- 1500678 TI - Reversible bile acid changes in bile duct obstruction and its potential for hepatocellular injury. AB - The etiology of hepatocellular dysfunction resulting from chronic biliary obstruction is not clearly understood. Alterations in bile acid metabolism due to changes in microsomal cytochrome P-450 enzyme activities may have a fundamental role in cholestatic liver injury. This study examines the very early changes in both biliary bile acids and hepatic microsomal cytochrome P-450 content after bile duct obstruction in the rat and the effects of the restoration of bile flow after 3 days of biliary obstruction. We found that early induction of cytochrome P-450 may be a fundamental step in the generation of cholestatic liver injury mediated by hepatotoxic bile acids. The rapid reversal of bile acid changes with reconstituted bile flow indicate that the liver is able to quickly recover when obstruction is relieved. Characterization of this fundamental process may ultimately provide a means of modulation of cholestatic hepatotoxicity. PMID- 1500679 TI - Caffeine clearance in cirrhosis. The value of simplified determinations of liver metabolic capacity. AB - Less complex methods of measuring hepatic metabolic capacity are needed. A simplified caffeine clearance test was evaluated in 23 patients with stable alcoholic liver disease. First, saliva caffeine concentrations were measured over a 24-h caffeine-free interval. Clearance was calculated from the rate of elimination of caffeine and an assumed volume of distribution and compared with the results of a formal clearance test using sequential plasma and saliva samples following a 300 mg oral dose. The simplified method was then assessed in 11 hospitalized patients with cirrhosis. Saliva caffeine concentrations remained measurable over the interval of study in 82% of patients. Caffeine clearance as determined by the simplified method did not differ from plasma caffeine clearance after an oral dose. Application of this method was achieved in 11 of 12 patients hospitalized for complications of severe liver disease, and revealed markedly diminished clearance. Thus, caffeine clearance can be accurately estimated in patients with severe liver disease using two or more samples of either saliva or plasma. This simplified determination of caffeine elimination rate provides a more practical assessment of hepatic metabolic capacity than a formal clearance test. PMID- 1500680 TI - Protein C in patients with alcoholic cirrhosis and other liver diseases. AB - The coagulation inhibitor protein C was measured in 151 patients with various liver diseases. The protein C level was significantly decreased in patients with alcoholic cirrhosis (n = 73) compared to patients with steatosis (n = 24) (40 +/- 2%) vs. 88 +/- 4%, mean S.E., p less than 0.001). It was also decreased in cases of acute liver damage (n = 8) and in patients with non-alcoholic cirrhosis (n = 15) (35 +/- 7% and 36 +/- 4%, respectively). A significant correlation was found between protein C and Normotest, antithrombin, heparin cofactor II, (r = 0.83, r = 0.82, r = 0.81, respectively, p less than 0.001). There was also a significant correlation between protein C and serum concentrations of albumin (r = 0.61, p less than 0.001), but a negative association to bilirubin (r = -0.56). No significant association was found between protein C and aspartate aminotransferase, alaline aminotransferase, and gamma-glutamyltranspeptidase. In conclusion, protein C is low in advanced liver diseases and gives the same amount and type of information as Normotest, antithrombin and heparin cofactor II. PMID- 1500681 TI - Course of hepatitis B and D virus infection in auxiliary liver grafts in hepatitis B-positive patients. A light-microscopic and immunohistochemical study. AB - Four patients who received an auxiliary partial liver graft for decompensated liver cirrhosis due to hepatitis B (HBV), associated in two cases with hepatitis D virus (HDV) superinfection, were studied. The sequential appearance of hepatitis B and D antigens in the grafts was investigated in serial liver biopsies by immuno-histochemical methods and compared with the viral antigenic profiles of the host livers. The histological changes in the liver grafts were studied in relation to the viral expression patterns. One week after transplantation, expression of HBsAg was already apparent in two grafts. HBcAg was found in the graft of the only patient with HBcAg in the host liver. HDAg was expressed in the grafts of both patients with HDV superinfection; in one of these cases HDAg was present without HBsAg. At 3 months, viral antigen expression was maximal. Expression of HBsAg and HBcAg in the grafts of the two HDV-positive patients was, however, less extensive than in the two HBV-positive patients. All patients developed a mild lobular hepatitis, histologically demonstrated between the 47th and 107th posttransplantation day. In the two HBV-positive, HDV-negative patients, cirrhotic transformation of the graft occurred within 1 year. In the HDV-positive patients only a mild chronic active hepatitis with slight or moderate fibrosis was observed after 1 year. We conclude that recurrence of HBV and HDV infection in auxiliary liver grafts is demonstrable within 1-3 weeks. HBV infection in liver grafts may be a rapidly progressive disease. Coinfection with HDV does not aggravate the acute hepatitis and may even suppress the progression of chronic HBV. PMID- 1500682 TI - Selenium in chronic liver disease. AB - In order to assess the role of selenium (Se) in chronic liver disease, we have measured serum, urinary and hepatic selenium in a range of liver diseases and correlated them with nutritional status and conventional liver biochemistry. Serum Se levels (microgram/l +/- S.D.) were significantly lower in both alcoholic (63.6 +/- 18.2, p less than 0.0001) and non-alcoholic liver disease (NALD) (60.6 +/- 13.6, p less than 0.0001) compared to healthy controls (87.8 +/- 21.2) and non-malignant 'disease controls' (80.3 +/- 19.1). Hepatic Se levels (microgram/g of dry weight) were also reduced in both ALD (0.568 +/- 0.647, p less than 0.005) and NALD (0.863 +/- 0.308, p less than 0.005) compared to controls (1.227 +/- 0.296), 24-h urinary Se excretion (microgram) in ALD (24.6 +/- 10.7) and NALD (29.0 +/- 14.3) was similar to controls (30.3 +/- 8.7). Serum Se showed a highly significant positive correlation with albumin (p less than 0.001) in both ALD and NALD. Serum levels were also significantly correlated with anthropometric measurements. Dietary assessment of patients with primary biliary cirrhosis and low serum Se levels did not show a reduced dietary intake. Our data show that Se levels are low in liver disease irrespective of aetiology and suggest that these low levels are more likely to be related to overall nutritional status than to dietary intake. PMID- 1500683 TI - Fasting gallbladder volume, postprandial emptying and cholecystokinin release in gallstone patients and normal subjects. AB - Since abnormal gallbladder emptying may be a contributing factor in the development of gallstone disease, we determined fasting gallbladder volume and postprandial contraction in 20 gallstone patients and 20 normal subjects with the aid of ultrasonography. Moreover, basal plasma cholecystokinin levels and postprandial cholecystokinin (CCK) release were determined. Gallstone patients were divided into strong contractors (13 pts) and weak contractors (below 95% confidence interval for AUC contraction in % during 90 min: 7 pts). Strong contractor patients had significantly larger mean fasting volumes than normal subjects (mean +/- S.E.: 34.9 +/- 6.1 ml and 18.9 +/- 1.6 ml, respectively). This was not true for weak contractor patients (mean fasting volume 23.2 +/- 3.2 ml). Both strong contractor and weak contractor patients had significantly higher mean residual volumes than normal subjects (17.0 +/- 4.1 ml, 18.0 +/- 2.9 ml, and 8.8 +/- 1.1 ml, respectively). Absolute gallbladder emptying was significantly higher for strong contractor patients than for normal subjects, but relative emptying was the same. Opposite patterns of CCK release occurred in gallstone patients and normal subjects. In normal subjects, more CCK release was associated with stronger gallbladder emptying. In contrast, weak contractor gallstone patients had significantly higher CCK release than strong contractor patients. (AUC CCK: 304 +/- 89 pmol/l x 90 min and 106 +/- 29 pmol/l x 90 min, respectively). The present study indicates that strong contractor gallstone patients may have large residual gallbladder volumes due to large starting volumes, whereas weak contractor patients may have large residual volumes due to impaired contraction. Subjects with large fasting and residual volumes may be at increased risk for gallstone disease.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1500684 TI - Polycystic hydatid disease (Echinococcus vogeli). Clinical, laboratory and morphological findings in nine Brazilian patients. AB - Polycystic hydatid disease occurs in neotropical zones and is caused by Echinococcus vogeli. The paca, a wild rodent, is the intermediate host and the final host is the dog. Seven cases of polycystic hydatid disease autochthonous to the Brazilian Amazon region are described. The disease was polycystic in all cases and diagnosis was based on anatomopathological findings. E. vogeli was identified by the shape and dimensions of the rostellar hooks. The liver was the organ most often involved (6/7), followed by the lungs (2/7) and mesentery (2/7), spleen (1/7) and pancreas (1/7). The main clinical manifestations were abdominal pain, hepatomegaly, jaundice, weight loss, anemia, fever, hemoptysis, palpable abdominal masses and signs of portal hypertension. Hepatic calcifications were detected in four cases. Two cases from the hinterland of the State of Sao Paulo are also reported. Both had calcified round structures in the liver, highly suggestive of calcified polycystic hydatids. The aim of the present report was to report on this relatively unknown hydatid disorder of Tropical America and to disseminate its clinical, ultrasound and radiological features. PMID- 1500685 TI - Phenotypical modulation of liver fat-storing cells by retinoids. Influence on unstimulated and growth factor-induced cell proliferation. AB - In conditions of chronic liver inflammation, liver fat-storing cells (FSC) differentiate into 'myofibroblast-like cells'. This transition is characterized by a gradual loss of vitamin A stores, and previous studies suggest a possible relationship between the intracellular retinoid content and the proliferative potential of this cell type. In the present study, we further characterized this aspect of FSC biology by monitoring ultrastructural changes and growth characteristics during several serial passages in culture. Our observations suggest that the complete transition to the 'myofibroblast-like phenotype' is paralleled by a sudden and remarkable increase in the growth rate. At this stage, cell growth appears rather independent from the presence of mitogens in the culture medium, suggesting cell transformation. Accordingly, the mitogenic effects of platelet-derived growth factor and epidermal growth factor appears reduced when compared to those observed in FSC retaining the original 'storing' phenotype. Incubation of vitamin A-depleted FSC with retinol and retinoic acid resulted in the partial recovery of intracellular retinoid stores and in a significant reduction of basal growth rate and basal and growth factor-induced DNA synthesis. In summary, these in vitro observations suggest that intracellular retinoids play a central role in the control of unstimulated and growth factor induced FSC proliferation and may help understand in vivo mechanisms leading to liver fibrosis. PMID- 1500686 TI - Anti-HBe-positive chronic hepatitis B with HBV-DNA in the serum response to a 6 month course of lymphoblastoid interferon. AB - Eighteen heterosexual HBsAg carriers with anti-HBe- and HBV-DNA-positive chronic hepatitis B (CHB) were randomly assigned to receive human lymphoblastoid interferon (ly-IFN) at a dose of 5 MU/m2 i.m. three times a week for 6 months (ten cases) or no treatment (eight cases). All patients were followed for 24 months after IFN discontinuation and received a second liver biopsy. During the 6 months of treatment all patients had a progressive reduction of serum HBV-DNA levels, and at the end of therapy nine out of ten were HBV-DNA-negative and had normal ALT values. None of the untreated patients became persistently HBV-DNA negative or showed significant variations of ALT levels. During the post treatment follow-up, from 1 to 17 months after ly-IFN discontinuation, eight of the nine responders (89%) had recurrent or persistent reappearance of HBV-DNA in the serum and reactivation of the liver disease activity, with an ALT peak in four of them. On the post-trial liver biopsy seven of the eight relapsed patients showed persistence of HBcAg reactivity with no significant difference in the percentage of positive cells with respect to the pre-treatment liver specimen. Histological features improved in four treated patients, worsened in one untreated case and were unchanged in the remaining patients. These results indicate that ly-IFN shows a transient antiviral effect in the therapy of anti HBe- and HBV-DNA-positive CHB. The 6-month treatment regimen employed in this study seems insufficient for eradicating the replicating virus from the liver cells in the majority of patients and consequently does not appear to prevent HBV reactivation after IFN discontinuation. PMID- 1500687 TI - Effects of an increase in protein intake on hepatic efficacy for urea synthesis in healthy subjects and in patients with cirrhosis. AB - The efficacy of urea synthesis as measured by functional hepatic nitrogen clearance (i.e., the relation of urea synthesis rate to blood alpha-amino nitrogen concentration) was studied before and after diet protein supplementation in six healthy subjects and five patients with stable cirrhosis (galactose elimination capacity about 60% of control). Daily protein intake was increased for 14 days by a protein-enriched liquid from (mean +/- S.D.) 1.01 +/- 0.32 g/kg body wt. to 1.62 +/- 0.31 g/kg body wt in the control subjects, and from 0.69 +/- 0.21 g/kg body wt. to 1.50 +/- 0.15 g/kg body wt. in the patients with cirrhosis. This increased the hepatic nitrogen clearance from 27 +/- 10 l/h to 39 +/- 15 l/h in the control subjects (p less than 0.05) and from 15 +/- 6 l/h to 21 +/- 7 l/h in the cirrhosis patients (p less than 0.05). There was no effect on the galactose elimination capacity in any group. Compared to the control subjects, the response in hepatic nitrogen clearance relative to the increase in protein intake was reduced by 60% in the patients. Basal glucagon was 75% higher in the patients and increased by 50% during high protein intake (p less than 0.05), but did not parallel the increase in hepatic nitrogen clearance, and it did not change in the control subjects. The study shows that an increase in protein intake selectively increases liver function with regard to disposal of amino nitrogen; the mechanism is qualitatively intact but quantitatively deficient in patients with cirrhosis of the liver, and does not seem to depend on glucagon. PMID- 1500688 TI - Pathophysiology of elevated ascites fluid cholesterol in malignant ascites. Increased ascites to serum relation of proteins and lipoproteins in patients with peritoneal carcinomatosis as compared to patients with cirrhosis of the liver. AB - The existence of marked elevations of ascitic fluid cholesterol has been observed in patients with peritoneal carcinomatosis compared to patients with cirrhosis and has been found useful in differential diagnosis. This finding could be caused by an enhanced movement of plasma lipoproteins into the peritoneal cavity. To test this hypothesis we determined the fasting concentrations of total, high density lipoprotein (HDL)- and low density lipoprotein (LDL)-cholesterol, apolipoprotein-A1 (apo-A1) and apolipoprotein-B (apo-B) in serum and ascites of 17 patients with cirrhosis and 16 patients with peritoneal carcinomatosis. The movement of proteins from plasma to ascites was calculated from the ascites/serum concentration ratios of six different sized proteins with a molecular mass ranging from 54 kDa to 971 kDa. Mean values (mg/dl) for total cholesterol (92.6 vs. 21.0), HDL-cholesterol (15.6 vs. 1.8), LDL-cholesterol (63.4 vs. 16.1), apo A1 (50.2 vs. 13.6) and apo-B (41.2 vs. 12.9) in ascites were significantly higher in peritoneal carcinomatosis than in cirrhosis. These differences could only partially be explained by the higher serum concentrations of these parameters in peritoneal carcinomatosis, but were mainly due to a lower selectivity for the movement of plasma proteins and lipoproteins into ascites (mean ascites/serum (A/S) ratio: 0.30-0.77) in peritoneal carcinomatosis as compared to cirrhosis (mean ascites/serum ratio: 0.11-0.21). In both groups about 85% of the total cholesterol in serum and ascites consisted of HDL- and LDL-cholesterol. These findings support the hypothesis that elevations in ascitic cholesterol in peritoneal carcinomatosis compared to cirrhosis are mainly caused by the increased movement of plasma HDL and LDL into the peritoneal cavity. PMID- 1500689 TI - Diuresis increases ascitic fluid opsonic activity in patients who survive spontaneous bacterial peritonitis. AB - Patients with low protein ascites and deficient ascitic fluid opsonic activity have been shown to be unusually predisposed to development of spontaneous bacterial peritonitis. Survivors of spontaneous peritonitis frequently develop recurrent infection. Diuresis has been shown to increase the ascitic fluid opsonic activity of patients who have never had spontaneous bacterial peritonitis. Patients with adequate opsonic activity are protected from ascitic fluid infection. Theoretically, the subset of patients who develop spontaneous peritonitis may have such severe liver disease that (i) their ascites is refractory to diuretic therapy or (ii) their ascitic fluid opsonic activity does not increase in response to diuresis. In this study, opsonic activity and concentrations of total protein and complement components were measured in the ascitic fluid of 11 patients who were hospitalized with spontaneous bacterial peritonitis and who responded to oral diuretics. The mean values of all of these parameters were found to increase significantly comparing the end-of-diuresis samples to the specimens that were diagnostic of ascitic fluid infection. Patients who survive spontaneous bacterial peritonitis are able to increase their ascitic fluid total protein and opsonic activity in response to diuresis. This increase in endogenous antimicrobial activity may help prevent recurrence of ascitic fluid infection. PMID- 1500690 TI - Hepatic oxidant and antioxidant systems in portacaval-shunted rats. AB - The purpose of the present study was to determine the effects of chronic portal diversion on antioxidant levels in the rat liver. Male Sprague-Dawley rats (n = 32) were used for these studies. An end-to-side portacaval anastomosis was constructed in 17 of the rats. Sham-operated rats (n = 15) served as controls. Two weeks later, hepatic blood flow was measured by the radioactive microsphere technique and the liver was harvested for biochemical measurement of catalase, manganese superoxide dismutase, copper-zinc superoxide dismutase, selenium glutathione peroxidase, xanthine oxidase, xanthine dehydrogenase and reduced glutathione (acid soluble sulfhydryls). Total hepatic blood flow was approx. 40% lower in portacaval-shunted rats when compared to sham-operated control rats. Total superoxide dismutase (SOD) and xanthine dehydrogenase (XD) levels were significantly reduced in the liver of shunted rats when compared to controls. Xanthine oxidase activity was unaltered. The decreased superoxide dismutase levels were exclusively due to reductions in the cytosolic Ca/Zn SOD; Mn SOD levels were unaltered. These data are consistent with oxidant stress and suggest that the liver of subjects with conditions characterized by decreased portal blood flow may be more susceptible to oxidant-induced liver injury. PMID- 1500691 TI - Aprindine-induced hepatic granulomata. AB - Aprindine is a very effective antiarrhythmic agent with a narrow therapeutic ratio. We report a patient who suffered from granulomatous hepatitis probably due to the administration of aprindine. Evidence of hepatitis appeared within 6 weeks of initiating aprindine therapy and resolved rapidly when the drug was withdrawn. Six months later, fibrosis but no granulomata were found in the expanded portal tracts. Our observations suggest that granulomatous hepatitis can occur during aprindine therapy. PMID- 1500692 TI - Selective intestinal decontamination in the prevention of bacterial infection in patients with acute liver failure. AB - To investigate whether selective intestinal decontamination from oral administration of poorly absorbable antibiotics is effective in preventing bacterial infection in patients with acute liver failure, the incidence of nosocomial infection in 34 patients consecutively admitted to hospital between 1985-1990 and treated with either neomycin + colistin + nystatin or norfloxacin + nystatin (group I) was compared to the incidence of infection in 57 patients who did not receive oral, poorly absorbable antibiotics and who were consecutively admitted between 1972-1984 (group II). Patients from groups I and II had similar clinical and laboratory data at hospital admission. Twelve patients from group I and 33 from group II developed bacterial infection during the study period. The probability of infection was significantly different (p = 0.0083) in the two groups: 19% vs. 39% at the 3rd day of admission, 33% vs. 74% at the 7th day, and 48% vs. 78% at the 14th day, respectively. This difference was due to a different rate of infection from enterobacteria. Enterobacteria caused one infectious episode in group I and 24 in group II (p less than 0.001). The incidence of infections caused by other organisms, however, was similar in both groups (15 and 19 episodes, respectively). These results suggest that selective intestinal decontamination is useful in reducing the risk of infection from enterobacteria in patients with acute liver failure. PMID- 1500693 TI - Hepatitis B x antigen and polymerase antibodies in the serum of hepatitis B carriers with or without hepatitis delta virus infection. Effects of interferon treatment. AB - Previous work has shown that the hepatitis B x antigen (HBxAg) and antibodies directed against the polymerase of hepatitis B virus (anti-pol) are early markers of hepatitis B virus (HBV) replication in natural infections. The present study was carried out to test the hypothesis that the appearance of one or both of these markers signaled reactivation in chronic carriers with liver disease who were treated with alpha-interferon (IFN). The results show that HBV DNA decreased among the patients who responded to therapy, and that among these responders, neither HBxAg nor anti-pol became detectable in serum for 12 months after treatment, in contrast to controls. Hence, the loss of HBxAg and anti-pol correlate with decreased levels of HBV DNA in response to IFN therapy. However, different patterns of HBxAg and anti-pol were observed among alpha-IFN-treated HBV carrier patients who were also chronically infected with the hepatitis delta virus (HDV). The treatment of such patients often resulted in the loss of HDV RNA from serum and delta antigen from liver. Most of these patients had increased levels of HBV DNA in serum. HBxAg and/or anti-pol also became detectable in patients who lost markers of HDV, implying that the suppression of HDV by IFN is accompanied by the appearance of early markers of HBV reactivation in some of the treated patients. PMID- 1500694 TI - Failure of acyclovir to enhance the antiviral effect of alpha lymphoblastoid interferon on HBe-seroconversion in chronic hepatitis B. A multi-centre randomized controlled trial. AB - Serum HBeAg levels and HBe-seroconversion were investigated in patients with chronic HBeAg-positive hepatitis who were randomized to receive either alpha lymphoblastoid interferon (5 megaunits subcutaneously daily for 16 weeks) plus acyclovir (2 g intravenously daily during weeks 1 and 2 and weeks 9 and 10) (n = 49) or no treatment (n = 48). HBeAg levels in serial dilutions of patient serum were assessed quantitatively by radioimmunoassay and compared with the values found for negative control serum. One year after the start of therapy 44 treated patients and 43 control patients were available for follow-up. A complete response (HBe-seroconversion) occurred in 11 treated patients (25%) and six controls (14%) (difference: 11%, 95% CI-5-28%). A partial response (HBeAg less than 50% of initial level) was found significantly more often for treated patients (n = 13, 30%) than for controls (n = 2, 5%) (difference: 25%, 95% CI 10 40%). During acyclovir-interferon combination therapy the decrease in HBeAg level was similar to that achieved during therapy with interferon alone. We conclude that acyclovir does not enhance the effect of interferon on serum HBeAg levels. Since HBeAg levels continue to decline during interferon treatment and rebound thereafter to pretreatment levels, prolongation of therapy may yield a higher response rate. PMID- 1500695 TI - Steatosis associated with immotile cilia syndrome: an unrecognized relationship? AB - The present study deals with a case of hepatic parenchymal steatosis in a child with primary ciliary dyskinesia (immotile cilia syndrome) well documented by functional and ultrastructural evaluation of the ciliary epithelia. Hepatic steatosis was associated with ultrastructural evidence of retention of material either in the cisternae of the endoplasmic reticulum or in proximity of the Golgi apparatus of hepatocytes. It is suggested that the absence of dynein in the axoneme is probably part of a diffuse genetic defect which may extend to cytoplasmic, non axonemal, dynein and lead to a disturbance of various microtubule-dependent cell activities. PMID- 1500696 TI - Frequency and significance of chronic ulcerative colitis in severe corticosteroid treated autoimmune hepatitis. AB - To assess the prevalence and significance of chronic ulcerative colitis in patients with severe autoimmune hepatitis and to determine the frequency of cholangiographic and histologic features of primary sclerosing cholangitis in those with colitis, 105 patients who had been screened by annual proctoscopic examination were studied. Patients with features of colitis were compared to counterparts without colitis who had been matched by age, sex, disease severity and treatment regimen. Seventeen patients (16%) had findings of chronic ulcerative colitis. Twelve of these underwent cholangiography and five (42%) had features of primary sclerosing cholangitis. Patients with and without cholangiographic abnormalities were indistinguishable by clinical, laboratory, immunoserologic, and histologic features. Fibrous obliterative cholangitis was present in only two patients, including one with normal cholangiography. Patients with colitis entered remission less frequently (59 vs. 94%, p less than 0.05), failed treatment more commonly (41 vs. 6%, p less than 0.05) and progressed to cirrhosis more frequently (75 vs. 25%, p less than 0.05) than counterparts without colitis. Patients with colitis but normal cholangiography, however, responded satisfactorily to therapy. We conclude that chronic ulcerative colitis can coexist with severe autoimmune hepatitis in the absence of primary sclerosing cholangitis or hepatitis C infection. Under such circumstances its presence does not adversely influence treatment outcome. Primary sclerosing cholangitis cannot be excluded by routine examinations and its presence is associated with a poor treatment response. Cholangiography should be considered in all patients with autoimmune hepatitis and colitis, especially in those recalcitrant to therapy. PMID- 1500697 TI - Hepatitis D virus superinfection remains a rare occurrence in non-drug abusers in Hong Kong. AB - Recent studies from Taiwan reported an increased prevalence of hepatitis D virus (HDV) superinfection as well as a spread of HDV infection to non-drug abusers. We examined the current prevalence of HDV superinfection in Hong Kong by testing sera from a large cohort of patients with acute and chronic hepatitis B virus (HBV) infection, collected between January 1988 and December 1990, for IgG antibody to HDV (anti-HDV). Anti-HDV was detected in 13 (93%) of 14 parenteral drug abusers who had HBV-related chronic liver disease. However, anti-HDV was detected in only one (0.15%) of 664 non-drug abusers who had chronic HBV infection and none of 31% patients with acute hepatitis B. We concluded that HDV superinfection remains a rare occurrence in non-drug abusers in Hong Kong. PMID- 1500698 TI - Uridine catabolism by the isolated perfused rat liver. AB - A new approach in the treatment of gastrointestinal tumors with 5-fluorouracil involves the infusion of high doses of uridine to improve the chemotherapeutic efficiency of the former. High amounts of uracil formed from uridine can interfere with the hepatic catabolism of 5-fluorouracil and thus increase its bioavailability and toxicity. In our study, we analysed the metabolite pattern of uridine in the effluent of isolated perfused rat livers in relation to portal uridine levels. The livers were perfused hemoglobin-free without recirculation at a constant flow. In the perfusate, uridine was changed from 0.5 to 100 mumol/l. The complete degradation of [2-14C]uridine and [2-14C]uracil was monitored via the release of labeled CO2. Radioactive catabolites of uridine including uracil and the sum of dihydrouracil and beta-ureidopropionate were separated by high performance liquid chromatography and counted using a radioactivity flow monitor. Portal uridine concentrations were increased from 0.5 to 100 mumol/l and were accompanied by a rise in the relative amount of non-metabolized uridine in the effluent from 13 to 78%. At uridine concentrations above 50 mumol/l, there was a constant release of uracil into the effluent, indicating saturation of uridine phosphorolysis or transport. The amount of 14CO2 formed by the liver reflecting complete uridine breakdown was higher than any other uridine metabolite when uridine concentration varied from 0.5 to 15 mumol/l. Saturation of 14CO2 formation was achieved at a uridine concentration of 25 mumol/l. Higher peak values of 14CO2 release were observed after direct infusion of equivalent amounts of uracil into the portal vein.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1500699 TI - Detection of serum HBV-DNA by polymerase chain reaction (PCR) in patients before reactivation of chronic hepatitis B. AB - Reactivation of chronic hepatitis B is characterized by the reappearance of HBV DNA in serum. The purpose of the study was to determine whether, before reactivation, HBV-DNA would be detectable in serum, using a sensitive procedure of detection, namely polymerase chain reaction (PCR). We studied 17 patients with chronic hepatitis B who experienced an episode of reactivation, defined by the reappearance of HBV-DNA in serum. None of these 17 sera had HBV-DNA demonstrable by dot-blot hybridization nor liquid hybridization in sera collected before reactivation. Using PCR, HBV-DNA was detected, before reactivation, in 13 of the 17 episodes of reactivation tested with Southern-blot and hybridization. HBV-DNA was not detectable with PCR in the serum of four patients who subsequently experienced an episode of reactivation. In conclusion, our results show low level HBV replication before reactivation in most, but not all, HBs-positive, HBV-DNA negative patients. This suggests that reactivation may occur even in patients with no HBV-DNA demonstrable in serum with PCR prior to reactivation. PMID- 1500700 TI - Determinants in the hepatic uptake of organic anions. PMID- 1500701 TI - Immunologic and molecular basis of viral persistence. The hepatitis B virus model. PMID- 1500702 TI - Gilbert's syndrome--a possible cause of hyperbilirubinemia after orthotopic liver transplantation. PMID- 1500703 TI - HCV in non-replicative chronic HBV infection. PMID- 1500704 TI - Problems in treating chronic HDV infection. PMID- 1500705 TI - Toxicity of diclofenac to isolated hepatocytes. PMID- 1500706 TI - Liver transplantation in carriers of the HBsAg: role of short-term passive prophylaxis with immunoglobulin. PMID- 1500707 TI - Immunoblot assay as diagnostic test for hepatitis C virus infection. PMID- 1500708 TI - Treatment of chronic type D hepatitis and concomitant human immunodeficiency infection with alpha-interferon. PMID- 1500710 TI - Abstracts of the 27th annual meeting of the European Association for the Study of the Liver. Vienna, Austria, 26-29 August 1992. PMID- 1500709 TI - Lymphoblastoid interferon in chronic hepatitis C patients, 'non-responders' to recombinant interferon-alpha (rIFN-alpha) PMID- 1500711 TI - Peptide-induced modulation of target cell sensitivity to natural killing. AB - We have previously shown that the capacity of class I molecules to confer resistance to NK in transfected target cells maps to the Ag-binding site (ABS) of the HLA class I structure. Here we examine the effect of peptide (reagents specific for the ABS) pretreatment on the NK sensitivity of class I+ target cells. Synthetic peptides (10-17 amino acids in length) were used to pretreat C1R target cells expressing either no serologically detectable HLA-A, B class I molecules, or C1R transfectants expressing individual HLA-A or -B locus class I molecules. In each case in which the class I allele had previously been shown to directly bind a given peptide, peptide-pulsing of target cells resulted in increased sensitivity to NK-mediated conjugation and cytolysis. The NK susceptibility of C1R target cells expressing no HLA-A, B class I molecules or the nonprotective HLA-A2.1 or HLA-A2M70 mutant class I molecules was unaffected by pretreatment with HLA-A2-binding peptides. These results support the intimate involvement of the HLA class I ABS and potentially ABS-bound peptides in determining target cell sensitivity to NK. Furthermore, these findings form the basis of an effective screening procedure for discerning peptide class I allele specific interactions. PMID- 1500712 TI - Activation of resting peripheral blood lymphocytes through the T cell receptor induces rapid phosphorylation of Op18. AB - Op18 is a highly conserved major cytosolic phosphoprotein that has been implicated in signal transduction in a wide variety of cell types. Freshly isolated peripheral blood lymphocytes (PBL) constitutively express low levels of mostly unphosphorylated Op18. After mitogenic stimulation of PBL, Op18 synthesis is induced at a time when cells are entering S-phase. In this study, we have examined the phosphorylation of Op18 in freshly isolated PBL after activation of the T cell receptor by OKT3. Quantitative analysis of Op18 phosphorylation was undertaken by metabolic labeling with 32Pi and PhosphorImager analysis of two dimensional gels. After 10 or 15 min of activation by OKT3, one of the three major phosphorylated forms of Op18, designated Op18c, increased approximately 10 fold, which represented a most pronounced change among a large number of phosphoproteins analyzed. In time course experiments, increased Op18 phosphorylation to yield Op18c was observed as early as 2 min. Continued OKT3 induced activation for 20 to 72 h resulted in a further increase in phosphorylated Op18 forms, which paralleled new Op18 synthesis and occurred at a time when cells were entering S-phase, as determined by [3H]-thymidine incorporation. Inhibitors of lymphoid proliferation, cyclosporin A and RPM, had no effect on early (less than 15 min) phosphorylation. Addition of calphostin C, a specific inhibitor of protein kinase C, 1 min prior to stimulation of resting T cells with OKT3 completely inhibited further phosphorylation of Op18. Incubation of PBL with calphostin C for 75 min decreased constitutive levels of phosphorylated Op18. In contrast, inhibition of cyclic nucleotide-dependent protein kinases with HA1004 had no effect on Op18 phosphorylation. Activation of cAMP-dependent protein kinase with Forskolin or 8Br-cAMP did not increase Op18 phosphorylation. Our results suggest that Op18 phosphorylation is mediated by protein kinase C activation as an early event in T cell activation through the T cell receptor. PMID- 1500713 TI - Mapping of the rabbit MHC reveals that class I genes are adjacent to the DR subregion and defines an insertion/deletion-related polymorphism in the class II region. AB - Molecular analyses of genes in the rabbit MHC (RLA) by pulsed field gel electrophoresis have shown that the relative order of class II genes (DP, DO, DQ, DR) is identical to that in humans and similar to that in the mouse. However, a major difference from either HLA or H-2 was observed at the DR end of the RLA class II complex: class I genes are located in close proximity to DR with no interposed class III sequences. A MluI fragment of 180 kb and a 210-kb SalI fragment both hybridized with the DR probe as well as with different class I probes including that for pR27, a class I gene with T cell-limited pattern of expression. Comparison of two different RLA haplotypes, A and B, indicated that the distance between the DQ and DR subregions differs by approximately 700 kb in the two haplotypes. Testing other unrelated rabbits suggested that this difference segregates within the rabbit population and presumably derives from an insertion/deletion event in different haplotypes. A further difference between the A and B haplotypes included variable distance between genes encoding DO beta and DP; the DR end of the complex and the class I genes linkage was conserved in the two haplotypes. PMID- 1500714 TI - VH genes in tandem array comprise a repeated germline motif. AB - In a study of human VH gene heterogeneity, we have previously used sequence specific oligonucleotide probes to demonstrate polymorphism of 56pl and three highly homologous VH3 germline elements. We now extend these findings with VH nucleotide sequences obtained from a person who possesses restriction fragments corresponding to each of these four VH3 genes. From a lambda-phage library of genomic DNA, distinct phage clones containing putative 56pl, hv3005, 1.9III, and hv3019b9 genes were selected by screening with oligonucleotide probes. PCR amplification, subcloning, and sequencing from the respective clones 3d216, 3d24, 3d28, and 3d277, yielded exact 56p1, hv3005, 1.9III, and hv3019b9 nucleotide sequences. A panel of oligonucleotide probes was shown to hybridize to these cloned VH3 genes with exact specificity, demonstrating the ability of the probes to predict the sequence of detected target DNA. Based on their chromosomal organization and their previously determined distribution in the population, these VH3 genes represent at least three distinct loci. From each of the VH3 containing phage clones, a VH4 element was also identified and sequenced. Linked to 3d24 and 3d28, respectively, were VH4 sequences identical to hv4005 and 1.9II, corroborating previous reports. The VH4 elements linked to 3d216 and 3d277 were distinct from published VH4 sequences. Nucleotide sequence homology was 97 to 99% among the VH3 sequences, and 93 to 99% among the VH4. These findings indicate that the VH3-VH4 gene pairs we have identified are a repeated germline motif, apparently resulting from multiple duplications of tandemly arrayed VH genes. PMID- 1500715 TI - VH-related idiotopes detected by site-directed mutagenesis. A study induced by the failure to find CD4 anti-idiotypic antibodies mimicking the cellular receptor of HIV. AB - The function of the CD4 cell surface protein as coreceptor on T helper lymphocytes and as receptor for HIV makes this glycoprotein a prime target for an immune intervention with mAb. A detailed understanding of the structural determinants on the therapeutic CD4 mAb that are involved in Ag binding or are recognized by anti-idiotypic mAb (anti-Id) may be important for designing antibodies with optimal therapeutic efficacy. Seven anti-Id raised against the CD4 mAb M-T310 were selected from a large panel with the intention to obtain CD4 mimicking structures with specificity for HIV gp120. The selected anti-Id did not react with other CD4-specific mAb cross-blocking M-T310. Among these, mAb M-T404, although having the same L chain as M-T310 and a VH region sequence differing only at 14 amino acid positions, was not recognized by the anti-Id. M-T310 H chain complexed with the J558L L chain reacted with all anti-Id, thus demonstrating that the recognized idiotopes are located within the VH region. To identify the idiotopes of M-T310 seen by the anti-Id, variants of M-T404 containing one or more of the M-T310-derived substitutions were generated by oligonucleotide-directed mutagenesis. The reactivity pattern of the mutant proteins with the anti-Id demonstrated that the idiotopes reside within the complementarity determining region (CDR) 2 and CDR3 loops of the VH region. A major idiotope was defined by a single amino acid in CDR2 that was recognized by three anti-Id, whereas the four other anti-Id reacted with determinants of CDR3. Although the performed amino acid substitutions did influence the Id recognition, Ag binding was not significantly affected, suggesting that none of the anti-Id can be considered as a mimicry of the CD4 Ag. PMID- 1500716 TI - IL-4 receptor signal transduction in human monocytes is associated with protein kinase C translocation. AB - IL-4 regulates B cell differentiation and monocyte functions. Protein kinases, such as kinase C (PKC), transduce receptor signals. The involvement of PKC in IL 4R signaling was investigated in human monocytes. Treatment with IL-4 (10 ng/ml) for 10 min resulted in a significant redistribution of the PKC activity from cytosol to nuclear fraction. Total PKC activity localized in the nuclear fraction of IL-4-treated and control monocytes was, respectively, 68 and 19%. In contrast, similar PKC activity was found in membrane fraction of IL-4-treated and control cells. The kinetics of IL-4-mediated redistribution of PKC activity to the nuclear fraction were rapid. Within 30 s of IL-4 exposure, 29% of the total PKC activity localized in the nuclear fraction as compared to 15% in control monocytes and increased to 69% at 10 min. The PKC activity in the nuclear fraction appears to be a sequestered form. Extraction with Triton X-100 and additional sonication were required for functional assay of PKC activity. Additional support for PKC involvement in IL-4R signaling is provided by the dose dependent effect of IL-4 on PKC activity and the abrogation of this effect after heat denature and immunoabsorption of IL-4. Furthermore, electron microscope examination and subcellular marker enzyme assays excluded significant contamination of the nuclear fraction by plasma membranes or subcellular organelles and IL-4 altering membrane disruption. The data presented indicate that IL-4R signaling in human monocytes involves PKC translocation to a nuclear fraction. PMID- 1500717 TI - Differences between ATP-mediated cytotoxicity and cell-mediated cytotoxicity. AB - There has been considerable recent interest in the possible role of extracellular ATP in cell-mediated cytotoxicity. To investigate the similarities and differences between ATP-mediated lysis and CTL-mediated lysis, we studied in detail the ATP-mediated lysis of EL-4 cells, which are highly susceptible to lysis by extracellular ATP. ATP-mediated lysis was time and concentration dependent; most lysis occurred within 4 to 6 h of incubation. The kinetics of ATP and cell-mediated lysis were similar. However, in contrast to CTL-mediated lysis, ATP-mediated lysis of EL-4 cells did not appear to be accompanied by characteristic chromosomal degradation (apoptosis). In order to compare these cytotoxic processes in greater detail, ATP-resistant clones were derived by growing EL-4 cells continuously in the presence of high concentrations of ATP. These cloned EL-4 lines showed marked resistance to ATP-mediated cytotoxicity across a wide range of concentrations but were as susceptible as the parent EL-4 cells to cell-mediated cytotoxicity by an alloreactive effector population from a MLC. Thus, there appear to be a number of differences between ATP-mediated and cell-mediated cytotoxicity in this system; most notable is the identification of cell lines that are resistant to ATP but susceptible to CTL-mediated lysis. PMID- 1500718 TI - Administration of human recombinant IL-7 to normal and irradiated mice increases the numbers of lymphocytes and some immature cells of the myeloid lineage. AB - In vitro experiments performed by several investigators have demonstrated that IL 7 is a growth factor for immature B lymphocytes, thymocytes, and mature T lymphocytes. To evaluate the potential therapeutic use for human rIL-7 (rhuIL-7) as a hematopoietin, we have studied the in vivo hematopoietic effects of rhuIL-7 in mice. In these experiments, sublethally irradiated and normal mice were treated with or without rhuIL-7 for up to 26 days. Administration of rhuIL-7 significantly increased the white blood cell count in the peripheral blood and spleen in both normal and irradiated mice. Treatment with rhuIL-7 also accelerated lymphocytic recovery in irradiated mice. Precursor and mature B lymphocytes showed the greatest expansion in response to rhuIL-7 administration, with smaller increases in T lymphocytes being observed. In mice recovering from high dose irradiation, rhuIL-7 treatment resulted in preferential expansion of CD8+ T lymphocytes and more rapid normalization of the CD4/CD8 ratios. Differential analysis of peripheral blood smears demonstrated that rhuIL-7 also increased the numbers of immature granulocytes in both normal and irradiated mice. Moreover, administration of rhuIL-7 to normal, irradiated, cyclophosphamide pretreated, or 5-fluorouracil-pretreated mice increased the number of acetylcholinesterase-positive megakaryocytes in the spleen, but not the bone marrow. Therefore, although the major in vivo effects of rhuIL-7 were on cells of the lymphocytic lineage, rhuIL-7 also increased the numbers of some immature cells of the myeloid lineage. PMID- 1500719 TI - IL-1 beta maturation: evidence that mature cytokine formation can be induced specifically by nigericin. AB - Mouse peritoneal macrophages stimulated with LPS produce large amounts of pro-IL 1 beta. When these cells were pulse-labeled with [35S]methionine, however, little labeled cytokine appeared in the medium after a chase, and that which was externalized was not processed to its mature biologically active form. In an effort to promote proteolytic maturation of IL-1 beta, macrophages were treated with agents that were expected to compromise their viability. The calcium ionophore A23187 and the detergent saponin caused complete release of nonprocessed 35-kDa pro-IL-1 beta and liberation into the extracellular medium of the cytoplasmic marker enzyme LDH and the lysosomal enzyme beta-N acetylglucosaminidase. Hypotonic lysis resulted in the release of a 20-kDa IL-1 beta species that was distinct from the 17-kDa mature species. Importantly, incubation of the murine macrophages with the potassium/proton ionophore nigericin led to a quantitative conversion of pro-IL-1 beta to a 17-kDa species. The N-terminus of this nigericin-derived product possessed the amino acid sequence expected for mature biologically active IL-1 beta. Monensin, an ionophore similar to nigericin, did not induce release or proteolysis of IL-1 beta. Complete release of mature IL-1 beta required concentrations of nigericin in excess of 2 microM and a minimum of 10 min of treatment. Mature 17-kDa IL-1 beta was observed within the nigericin-treated cells before their lysis. Nigericin's effect was not limited to mouse peritoneal macrophages, inasmuch as the ionophore also induced release and proteolytic maturation of IL-1 beta produced by LPS-stimulated human peripheral blood monocytes. Treatment of macrophages with LPS and nigericin, therefore, results in a unique series of intracellular events that promote formation of mature 17-kDa IL-1 beta. PMID- 1500720 TI - CD11b (Mac-1): a marker for CD8+ cytotoxic T cell activation and memory in virus infection. AB - We have found that CD11b, a cell surface integrin of macrophages, granulocytes, and NK cells, is expressed by a subset of CD8+ T cells that include both the active virus-specific CTL and the virus-specific memory CTL populations. CD8+CD11b+ cells comprise less than 3% of naive mouse splenocytes, but after lymphocytic choriomeningitis virus (LCMV) infection increase by 9- to 12-fold by the peak (day 8) of the virus-specific CTL response. Depletion of day-8 splenocytes with anti-Mac-1 and C' or enrichment by sorting for CD11b+ or CD8+CD11b+ spleen cells demonstrated that LCMV-specific CTL are CD11b+. The CD11b+ subpopulation also contained the bulk of the IL-2-responsive CD8+ cells. MEL-14, a homing marker down-regulated on activated T cells, was down-regulated on the majority of CD8+ cells that became CD11b+. Less than 1% of LCMV-immune splenic lymphocytes expressed CD11b. Antibody and C' depletion of this population severely impaired the ability of immune splenocytes to respond to in vitro secondary stimulation with LCMV-infected peritoneal macrophages, but did not affect the generation of a primary allospecific CTL response in MLC. Mixing of CD8-depleted and CD11b-depleted LCMV-immune splenocytes failed to restore the ability of these cells to mount a virus-specific memory CTL response, indicating that a cell coexpressing CD8 and CD11b is essential for this response. As determined by limiting dilution analysis, the precursors for the LCMV-specific memory CTL response were enriched in the CD11b+ population of LCMV-immune splenocytes. CD11b stained far fewer CD8+ splenocytes from naive mice than did CD44 (Pgp-1), and among immune splenocytes it identified a small subpopulation of CD44hi cells, indicating that CD11b may be the best single marker available for discriminating between naive and memory CD8+ T cells. PMID- 1500721 TI - Biosynthesis and secretion of complement component (C3) by activated human polymorphonuclear leukocytes. AB - We tested the hypothesis that human polymorphonuclear leukocytes (PMN), bearing complement receptors CR1 and CR3, might also synthesize C3, particularly when activated by LPS or cytokines. Northern blot analysis of total RNA, obtained from purified PMN stimulated overnight with LPS or cytokines (IFN-gamma, TNF-alpha, and IL-1) showed the 5.3-kb RNA transcript reported for C3 in hepatocytes and monocytes. No transcripts for C4 and factor B were detected. Time course studies of C3 mRNA expression in PMN treated with LPS or TNF-alpha demonstrated a steady increase with a plateau at 24 h that correlated with secretion of C3, determined by ELISA. In contrast, IFN-gamma and IL-1 induced a transient increase in C3 transcript with a peak around 8 h after stimulation, which was not reflected in an increased rate of C3 secretion. The content of C3 protein in PMN culture media, measured by ELISA, was about 4 ng/ml/10(7) cells after overnight stimulation with LPS or TNF-alpha. A very small amount of C3 (about 0.7 ng/ml/10(7) cells) was detected in supernatants from unstimulated and IFN-gamma- or IL-1-induced PMN. Immunoprecipitation with a polyclonal anti-human C3, followed by SDS-PAGE analysis, from [35S]methionine labeled PMN, revealed the presence in culture supernatants of three major bands at 185, 115 and 70 kDa, corresponding to pro-C3, alpha and beta chains, respectively. Analysis of [14C]methylamine incorporation and of autolytic cleavage showed that the C3 produced in tissue culture by PMN contained an intact thiolester bond. The capacity of PMN to secrete functional C3 in response to LPS and TNF-alpha might be an important mechanism of host defense at sites of inflammation. PMID- 1500722 TI - Inhibition of phospholipase A2 activity in guinea pig eosinophils by human recombinant IL-1 beta. AB - The effect of human rIL-1 beta on the release of arachidonic acid (AA) and on the phospholipase A2 (PLA2) activity in guinea pig eosinophils was investigated. Stimulation of [3H]AA-labeled eosinophils with the ionophore A23187 resulted in a time and concentration-dependent release of AA in parallel to hydrolysis of endogenous phosphatidylcholine (PC). Both events were abrogated by the chelation of intracellular free calcium, but not by its depletion from the medium, suggesting that the ionophore-induced AA release involves a PLA2 activity dependent on the mobilization of intracellular calcium. Addition of human rIL-1 beta (0.01 to 100 ng/ml) to eosinophils for 15 min had no effect on the release of AA induced by the ionophore. However, prolonged incubation with human rIL-1 beta (30 to 180 min) inhibited in a concentration- and time-dependent manner the release of AA and the hydrolysis of phosphatidylcholine in ionophore-stimulated eosinophils. Our results also showed that eosinophil homogenates contain a calcium-dependent PLA2 whose activity was markedly reduced when eosinophils were pretreated with human rIL-1 beta. The inhibition was time and concentration dependent and was observed in the presence of calcium and phospholipid excess. Finally, studies with Fura-2-loaded eosinophils showed that the ionophore A23187 stimulated an increase in intracellular calcium concentration that was not altered by pretreating the eosinophils with human rIL-1 beta. These results suggest that human rIL-1 beta inhibits the release of AA by eosinophils via the inhibition of a PLA2 activity and through a calcium-independent mechanism. Inhibition by human rIL-1 beta required a prolonged incubation (30 to 180 min) and was observed after its removal from the medium, suggesting that human rIL-1 beta did not interact directly with the PLA2 itself, but with a metabolic process involved with the regulation of its activity in eosinophils. PMID- 1500723 TI - Comparison of actin changes and calcium metabolism in plastic- and fibronectin adherent human neutrophils. AB - Human neutrophils adherent to a polystyrene plastic surface are vigorously activated, whereas those adherent to fibronectin manifest only a priming response. The basis of these metabolic differences was further characterized; polystyrene-adherent cells, which were shown to spread quickly upon adhesion, exhibited an increase of cytoskeleton-associated actin (F-actin) (measured by a nitrobenzoxadiazole-phallacidin fluorescent staining assay) and a decrease of monomeric G-actin concentration (measured by a DNase inhibition assay); in contrast, fibronectin-adherent cells exhibited little spreading and decreased their F-actin, after 1.5 min of adhesion, to 33.49 +/- 6.9% (mean +/- SD, n = 5) of initial levels found in suspended cells before plating. Actin depolymerization in fibronectin-adherent cells was confirmed by measuring G-actin, which sharply increased during the first minute of adhesion, rising from 0.065 +/- 0.007 to 0.20 +/- 0.035 microgram/microgram of protein (mean +/- SEM, p less than 0.05), and then remained elevated during 5 min of observation. In contrast, soluble fibronectin induced a decrease of G-actin in suspended cells. Cells pretreated with 1 microM cytochalasin D and allowed to adhere to a plastic surface did not spread, failed to generate O2-, and exhibited elevated concentrations of G-actin (0.1 to 0.2 microgram/microgram of protein) during the 5 min of observation. Actin changes, as well as respiratory burst, in adherent cells were shown to proceed through a pertussis toxin-insensitive pathway. Fluo-3 measurements of intracellular Ca2+ concentrations ([Ca2+]i) showed a fourfold and twofold [Ca2+]i increase in polystyrene- and fibronectin-adherent cells, respectively, after 2 min. The small rise in [Ca2+]i in fibronectin-adherent cells corresponds to a primed response of these cells to subsequent activation with FMLP. Ionomycin (1 microM) added to neutrophils just before adhesion on fibronectin induced full activation, i.e., O2- production and actin polymerization. The metabolic events controlling metabolic priming and actin depolymerization are as yet uncharacterized, but fibronectin receptor-linked responses beyond the mediation of cell adhesion have now been identified, suggesting complex metabolic functions of integrin receptors. PMID- 1500724 TI - Neutralization of HIV-1 by anti-idiotypes to monoclonal anti-CD4. Potential for idiotype immunization against HIV. AB - Anti-idiotypic antibodies were raised in rabbits against a panel of 11 murine mAb directed to the human CD4 receptor. Selection of mAb for vaccination was based on inhibition studies demonstrating that these mAb recognized CD4/V1 epitopes implicated in HIV-1-gp120 binding. Purified antisera showed high titer anti-Id activity and reacted specifically with Ag-combining site-related Id of the mAb used for their generation. Anti-Id either detected a private Id of the immunizing mAb or displayed a partial cross-reactivity with Id of other mAb to CD4. Eight anti-Id to six different mAb were shown to recognize determinants of recombinant HIV-1-gp120 or of HIV-1-gp160 as shown by ELISA and radioimmunoprecipitation assay. These anti-Id were capable of inhibiting HIV infection up to 100% in a MT 4 cell assay in vitro. In addition to neutralizing infectivity of cell-free virus, anti-Id to two mAb--the mAb IOT4a and 7.3F11--were also shown to inhibit HIV-induced syncytia formation up to 100%. Anti-Id to the mAb IOT4a, 7.3F11, and to the mAb anti-Leu3a interfered with rgp120 binding to cellular CD4 as assessed by flow cytometry. These results demonstrated that mAb specific for both CDR2- and CDR3-like regions of CD4 were capable of inducing HIV-1-gp120 cross-reacting anti-Id neutralizing HIV-1 in vitro. These studies may have implications for the development of a gp120 internal image based vaccine against HIV. PMID- 1500725 TI - Role of cytokines in alveolar macrophage accessory cell function in HIV-infected individuals. AB - Mononuclear phagocytes, including alveolar macrophages (AM), can be chronically infected with HIV and thus serve as a reservoir for the virus. Acting as AC during the generation of an immune response, HIV-infected mononuclear phagocytes can facilitate viral T cell infection by several mechanisms, including direct contact of T cells with HIV-infected macrophages as well as cytokine-induced up regulation of latent T cell infection. Our laboratory has shown that AM from HIV infected individuals have enhanced AC function compared to normal AM. In this study we explored AM production and secretion of IL-1 beta and IL-6, two cytokines critical for optimal AC function, in normal volunteers and HIV-infected patients. Cultured AM supernatants and lysates were generated in the presence and absence of LPS and standard mitogens. In initial mixing experiments HIV AM supernatants enhanced mitogen-induced T cell proliferation using normal AM as AC significantly more than normal AM supernatants, suggesting that HIV AM secreted more T cell stimulatory factors than normal AM. Neither group could enhance T cell proliferation induced by HIV AM suggesting these cells already secreted optimal levels of these factors. AM from HIV+ individuals produced and secreted more IL-1 beta (measured by ELISA) and IL-6 (measured in a B9 bioassay and by immunoprecipitation) than normal AM both spontaneously and in the presence of low LPS concentrations and mitogens. In some cases depleting HIV AM supernatants of IL-1 beta and IL-6 on immunoaffinity columns abrogated their enhancement properties indicating that these cytokines were important in the observed enhancement. However, in other patients different factors must also be involved as depletion of IL-1 beta and IL-6 in their AM supernatants had no effect on enhancement function. These results show that HIV AM secretory products are important in the enhanced AC function demonstrated by these cells. However, although augmented IL-1 beta and IL-6 secretion likely contribute significantly to this enhancement, other AC secretory factors and/or functions must also be involved. PMID- 1500726 TI - Cytokine patterns of immunologically mediated tissue damage. AB - Reactional states in leprosy are produced by different immunologic mechanisms and are responsible for a major component of tissue damage of the disease. Reversal reactions exhibit increased CD4 T cell infiltration in lesions and augmented cell mediated immune reactivity to Ag of Mycobacterium leprae that can rapidly produce nerve damage. Erythema nodosum leprosum (ENL) reactions also have CD4 T cell infiltration but appear to be associated with the formation of immune complexes that are responsible for panniculitis, arthritis, vasculitis, and nerve injury. Because these reactional states may serve as paradigms for other types of human immunologically mediated tissue damage, this study sought to characterize the dynamic changes in cytokines associated with these reactions. Expression of cytokine mRNA in lesions of leprosy reactional states were measured by PCR. In reversal reactions, IL-1 beta, TNF-alpha, IL-2, and IFN-gamma mRNA were prominent and found to increase during the reaction, concomitant with decreases in expression of mRNA for IL-4, IL-5, and IL-10. In ENL, selective increases in the expression of IL-6, IL-8, and IL-10 mRNA was observed, with persistent expression of IL-4 and IL-5 mRNA. Reversal reactions represent naturally occurring delayed type hypersensitivity reactions that favor macrophage activation and protective immunity, but which can engender concomitant cell injury. In contrast, ENL lesions represent immediate-type hypersensitivity reactions reflecting the selective stimulation of cytokines that attract neutrophils, stimulate antibody production, and down-regulate macrophage activation. The analysis of cytokine dynamics within different inflammatory responses can provide insights into immune mechanisms of tissue damage, and provide a useful framework for developing strategies for therapeutic intervention. PMID- 1500727 TI - A flow-cytometric method to study DNA fragmentation in lymphocytes. AB - A method to measure DNA fragmentation cell by cell in a cell population was implemented based on acridine orange procedure to determine DNA content of single cells by flow cytometry. Using this method it can be observed that the fragmentation process induced by irradiation in thymic cells occurs in a fraction of the population, thus indicating that this process is not evenly distributed over the total population, and that it corresponds to a fast phenomenon in which the cells suddenly lose DNA material. PMID- 1500728 TI - Biological activities of polyethylene-glycol immunoglobulin conjugates. Resistance to enzymatic degradation. AB - Serum IgG has been covalently bonded to polyethylene glycols of either 2000 or 8000 molecular weight to produce immunoglobulin conjugates with 4.4-27.2% of primary amines bonded to polyethylene glycol. Polyethylene glycol immunoglobulin conjugates retain the ability, comparable to native IgG, to bind to a range of protein and microbial antigens, but have a reduced ability to bind to Fc receptors or to fix complement C3. When 6.8% or more of available primary amines are conjugated, IgG-PEG conjugates are impervious to trypsin, and at 14% or more conjugation, more resistant than native IgG to pepsin and chymotrypsin. We suggest that PEG-Ig conjugates may be useful for the oral treatment of various gastrointestinal diseases in which secretory humoral immunity is insufficient. PMID- 1500729 TI - Characterization of monoclonal antibodies physically adsorbed onto polystyrene latex particles. AB - The physicochemical and immunochemical properties of monoclonal antibodies (MAbs), adsorbed onto polystyrene latex particles, have been investigated. Both native and pH 2 pretreated MAbs were compared before and after immobilization. It was found that the antigen binding capacity of the immobilized, acidic pretreated MAbs was significantly higher than for the immobilized, native IgG molecules. This enhanced antigen binding capacity appeared to be due to an improved molecular orientation following adsorption of the monomeric, pH 2 treated IgG fraction. Additionally, experiments using F(ab')2 fragments demonstrated that the Fc portion of the MAb molecule is of major importance for achieving the enhanced binding capacity. Binding studies showed that the (apparent) affinity of native and pH 2 pretreated MAbs were similar; the K(a) values of the immobilized MAbs were higher than those of MAbs in solution. PMID- 1500730 TI - U937 cells stimulated with opsonised zymozan particles provide a convenient laboratory source of tumour necrosis factor alpha. AB - The U937 cell line has been shown to generate tumour necrosis factor alpha (TNF alpha) in response to soluble stimuli such as PMA and LPS, but only after treatment with GM-CSF. We report here the generation of TNF-alpha from U937 cells following phagocytosis of opsonised zymozan particles without the need for pre treatment with GM-CSF. The release of TNF-alpha from U937 cells was demonstrated by a specific radioimmunoassay, L929 cell killing and neutrophil 'priming'. The biological activities in the cell supernatant were inhibited by TNF-alpha antiserum. Phagocytosis was required for TNF-alpha production. Non-opsonised zymozan or latex particles which were not phagocytosed or pretreatment with cytochalasin B, which inhibited phagocytosis of opsonised zymozan particles, all failed to trigger TNF-alpha production. Phagocytosis failed to trigger detectable IL-1 generation, and production of IL-6 was insufficient to produce biological effects on neutrophils. The U937 supernatant thus provides a source of human TNF alpha which can be generated conveniently and cheaply for experimental investigations. PMID- 1500731 TI - Evaluation of biological response modifiers in the enhancement of tumor uptake of technetium-99m labeled macromolecules. A preliminary report. AB - Imaging tumors with radioactive monoclonal antibodies remains attractive but continues to be challenging. With the hypothesis that the use of biological response modifiers (BRMs) may augment the tumor uptake, technetium-99m(99mTc) labeled tumor necrosis factor (TNF) and nuclear histone specific TNT-1-F(ab')2 were evaluated in tumor bearing mice given a single dose of interferon (IFN). Ukrain or pokeweed mitogen as BRMs. As early as 1.5 h post injection (p.i.) of the radioactive macromolecules, the absolute tumor uptake (% administered dose/g) of each agent was enhanced (e.g., TNF, control = 1.8 +/- 0.4, Ukrain = 3.2 +/- 0.5, P = 0.006) and tumor to muscle ratios were elevated (e.g., TNF, control a 4.1 +/- 2.2, interferon 8.3 +/- 2.7, P = 0.01). The absolute tumor uptake remained practically unchanged at 4 h p.i. Generally with BRMs, the blood clearance was rapid and tumor/blood ratios and tumor/muscle ratios were higher than in the control group, increasing to greater than 200% for IFN as a BRM. The early enhancement in tumor uptake of macromolecules, leading to excellent delineation of tumors by scintigraphy is highly encouraging and warrants further studies to explore the full potential of BRMs. PMID- 1500732 TI - Quantitative dot-blot assay for proteins using enhanced chemiluminescence. AB - A sensitive non-radioactive method for detection of specific proteins on Western blots is commercially available. The protein is immobilized on nitrocellulose membrane and immunolabelled with HRP-conjugated secondary antibody. HRP catalyzes the oxidation of luminol, a cyclic diacylhydrazide, resulting in the emission of light which is recorded on film. Using dot blot, we have shown that the signal generated by this system is proportional to the amount of protein loaded onto the membrane. Standard curves were linear (r2 greater than 0.95) over a 10-50-fold range. Linearity was also achieved with tissue extracts probed for a specific antigen. The sensitivity of the method is such that less than 10 fmol protein can be measured. The sensitivity and range are comparable to a previously reported dot-blotting assay based on the use of 125I-protein A, but the method does not require the handling of radioactive compounds. This method was used to estimate the level of chromogranin A in a mixture of proteins extracted from human brain. PMID- 1500733 TI - Isolation of functionally active intraepithelial lymphocytes and enterocytes from human small and large intestine. AB - A mild purification method has been developed for the isolation of human intraepithelial lymphocytes (IEL) and enterocytes from the same individual. The isolation procedure includes mechanical disruption of the mucosal layer, treatment with reducing agent and sedimentation followed by Percoll gradient centrifugation. Finally, epithelial cells are removed from the IEL fraction using magnetic beads coated with the anti-epithelial antigen monoclonal antibody (mAb) BerEP4. Leucocytes are removed from the enterocyte fraction using magnetic beads coated with mAbs directed against common leucocyte antigen (CD45). Using this procedure IEL and enterocytes have been isolated from apparently normal jejunal, ileal and colonic tissue specimens. Recoveries of IEL were 7 x 10(5), 4 x 10(5) and 1 x 10(5)/cm2 mucosa from jejunum, ileum and colon respectively. 1-2 x 10(6) enterocytes/cm2 mucosa were recovered from small intestine while the corresponding value for colonic biopsies was approximately 2 x 10(5) enterocytes/cm2. The IEL fraction was pure as judged by the low percentages of B cells, macrophages and BerEP4 positive cells (less than 4%) present in the purified fraction. The enterocyte fraction contained less than 2% CD45+ cells. The two cell fractions were viable and expanded in vitro. Enterocytes expanded spontaneously while IEL required initial stimulation with mitogens. The isolation procedure described here will make it possible to study the function of human IEL, interactions between IEL and enterocytes and the role of both cell types in local immunity. PMID- 1500734 TI - Immunology of Giardia and Cryptosporidium infections. AB - Giardiasis and cryptosporidiosis occur in immunocompetent persons, and as opportunistic infections in immunocompromised individuals. The causative organisms of giardiasis (Giardia lamblia) and cryptosporidiosis (Cryptosporidium parvum) have markedly different life cycles, but currently available evidence suggests that intestinal antibody plays a major part in host protection against both parasites. In the case of G. lamblia, the evidence points to a role for intestinal antitrophozoite antibody in blocking adherence of trophozoites to intestinal epithelium, with consequent removal of trophozoites from the intestine by peristalsis. Similarly, recent work supports the view that C. parvum infection can be prevented or interrupted by antibody that binds to Cryptosporidium life cycle stages present in the intestinal lumen (sporozoites and merozoites). Molecular characterization of G. lamblia and C. parvum immunodominant antigens would facilitate future studies aimed at determining whether vaccination against giardiasis or cryptosporidiosis is feasible. PMID- 1500735 TI - Deficient polymorphonuclear cell and mononuclear cell antibody-dependent cellular cytotoxicity in pediatric and adult human immunodeficiency virus infection. AB - Children with human immunodeficiency virus (HIV) infection have impaired polymorphonuclear leukocyte (PMNL) function leading to secondary bacterial infections and possible acceleration of underlying viral disease. The chief antiviral defense mechanism of PMNL is antibody-dependent cellular cytotoxicity (ADCC). Accordingly, the ADCC of PMNL and mononuclear cells from HIV-positive children was compared with that of HIV-positive adults, healthy adults, and age matched healthy children. PMNL and mononuclear cells from HIV-positive children incubated with hyperimmune HIV immune globulin (HIVIG) gave significantly lower ADCC compared with PMNL or mononuclear cells of healthy age-matched children incubated with HIVIG (P less than .05). The ADCC of mononuclear cells of healthy adults in the presence of plasma from HIV-infected children was significantly less than that of the same cells in the presence of plasma from HIV-positive symptomatic or asymptomatic adults. Augmentation of ADCC of the PMNL from HIV positive children with interferon-gamma or granulocyte-macrophage colony stimulating factor did not occur. Thus, the defect in ADCC of HIV-positive children is due to defects of both effector cells and antibody function. PMID- 1500736 TI - Antibody response to rubella virus antigen and structural proteins in retinitis pigmentosa. AB - Elevated serum ELISA IgG antibodies to rubella virus (RV) were found by three independent determinations in 41 (72%) of 57 adults with the retinal degeneration retinitis pigmentosa, while antibody responses to five other common neurotropic viruses were normal. However, these patients lacked clinical signs of active RV infection or known recent RV exposure, and 56 lacked IgM anti-RV antibody. Unusual relative percentages of IgG antibody to RV structural proteins compared with those of controls were found in patients' sera by radioimmunoprecipitation assay. For retinitis pigmentosa patients, percentage of RV envelope glycoprotein E1 antibody was similar to, of RV envelope glycoprotein E2 antibody was greater than, and of antibody to RV nucleocapsid C protein was lower than control percentages. Abnormal immunity to RV was also suggested by a lack of increased proliferation of lymphocytes to RV antigen despite elevated anti-RV antibody in patients with retinitis pigmentosa. Not associated with age or particular genetic pattern, these divergences from normal immunity suggest an unusual association between RV proteins and retinitis pigmentosa. PMID- 1500737 TI - Meningococcal disease and influenza-like syndrome: a new approach to an old question. AB - The temporal and spatial association of meningococcal disease and influenza-like syndrome (ILS) was assessed from surveillance data on these diseases in France for a 6-year period (1985-1990). Using time series methods to account for the usual seasonal pattern meningococcal disease, the incidence of meningococcal disease in a given week was found to be linked to incidence of ILS in the 5 previous weeks but not to that in subsequent weeks. Geographic spread of meningococcal disease correlated with spread of ILS. This study also suggests that meningococcal disease is more severe for a 2-month period during and after an ILS epidemic: The proportion of cases with purpura fulminans increased by 24% and those resulting in death by 26% during this period. No shift in the age distribution was observed. When an ILS epidemic is identified, medical practitioners should be informed of the likelihood of an increased incidence and severity of meningococcal disease. PMID- 1500738 TI - Lactate and glucose concentrations in brain interstitial fluid, cerebrospinal fluid, and serum during experimental pneumococcal meningitis. AB - Metabolic abnormalities during bacterial meningitis include hypoglycorrhachia and cerebrospinal fluid (CSF) lactate accumulation. The mechanisms by which these alterations occur within the central nervous system (CNS) are still incompletely delineated. To determine the evolution of these changes and establish the locus of abnormal metabolism during meningitis, glucose and lactate concentrations in brain interstitial fluid, CSF, and serum were measured simultaneously and sequentially during experimental pneumococcal meningitis in rabbits. Interstitial fluid samples were obtained from the frontal cortex and hippocampus by using in situ brain microdialysis, and serum and CSF were directly sampled. There was an increase of CSF lactate concentration, accompanied by increased local production of lactate in the brain, and a decrease of CSF-to-serum glucose ratio that was paralleled by a decrease in cortical glucose concentration. Brain microdialysate lactate concentration was not affected by either systemic lactic acidosis or artificially elevated CSF lactate concentration. These data support the hypothesis that the brain is a locus for anaerobic glycolysis during meningitis, resulting in increased lactate production and perhaps contributing to decreased tissue glucose concentration. PMID- 1500739 TI - Prophylaxis against wound infection following herniorrhaphy or breast surgery. AB - The effect of perioperative antibiotic prophylaxis on definite wound infections was assessed for 3202 herniorrhaphies or selected breast surgery procedures. Patients were identified preoperatively and monitored for greater than or equal to 4 weeks. Thirty-four percent of patients (1077/3202) received prophylaxis at the discretion of the surgeon; 86 definite wound infections (2.7%) were identified. Prophylaxis recipients were at higher risk for infection, with a higher proportion of mastectomies, longer procedures, and other factors. Patients who received prophylaxis experienced 41% fewer definite wound infections (odds ratio [OR], 0.59; 95% confidence interval [CI], 0.35-0.99; P = .04) and 65% fewer definite wound infections requiring parenteral antibiotic therapy (OR, 0.35; 95% CI, 0.15-0.88; P = .02) after adjustment for duration of surgery and type of procedure. Additional adjustment for age, body mass index, the presence of drains, diabetes, and exposure to corticosteroids did not change the magnitude of this effect meaningfully. The effect of prophylaxis was similar for all procedures studied. In the absence of formal guidelines, surgeons at these institutions administered prophylaxis preferentially to patients at highest risk. PMID- 1500740 TI - Participation of complement in the phagocytosis of the conidia of Aspergillus fumigatus by human polymorphonuclear cells. AB - Nonspecific immunity plays a major role in the clearance of the opportunistic fungal pathogen, Aspergillus fumigatus. However, the mode of recognition of Aspergillus conidia by the different elements of an intact phagocyte system remains poorly understood. This study concentrated on the initial interaction between infective conidia and human polymorphonuclear cells (PMNL) using a double label immunofluorescent method. At 37 degrees C, association was rapid. Although ingestion rates were slower than association, both association and ingestion plateaued at 90 min and were considerably reduced in the presence of fetal calf serum. In the presence of autologous plasma, association increased as the conidia to-cell ratio increased, but the percentage of associated conidia that were ingested decreased. At 4 degrees C, phagocytosis was negligible. Phagocytosis experiments in the presence of plasma treated in various ways to inhibit the complement pathways demonstrated that optimal association was dependent on an active alternative complement pathway. PMID- 1500741 TI - Adherence of Candida albicans to tissues from mice with drug- or radiation induced immunodeficiencies. AB - Host factors that influence binding of Candida albicans to murine spleen, lymph node, and kidney were studied. Organs were harvested from BALB/cByJ and AKR/J mice immunocompromised by irradiation, cyclophosphamide, and cortisone acetate alone or in combination. Tissues from treated mice and untreated littermates were compared for their ability to bind C. albicans in ex vivo assays. Immunosuppressive regimens decreased yeast binding to splenic marginal zones, but when mice recovered for 5 days after treatment, adherence to spleen was similar to adherence in untreated littermates. Adherence to lymph node and kidney in treated mice was not different from binding to these tissues in untreated mice. Total serum immunoglobulin titers correlated with binding of yeast cells to mouse spleen. Blocking studies ruled out a mannosyl-fucosyl receptor-mediated binding. These results suggest that ex vivo adherence of C. albicans represents a host immune defense mechanism by which the immunocompetent host binds blood-borne yeast cells to host immune cells in reticuloendothelial organs to prevent dissemination to other organs. PMID- 1500742 TI - Cytokine gene expression of endothelial cells infected with Trypanosoma cruzi. AB - Coronary microvascular spasm and platelet hyperreactivity have been implicated in the pathogenesis of Chagas' cardiomyopathy. To clarify further the role of the microvasculature in this disease, alterations in cytokine gene expression due to Trypanosoma cruzi infection of human umbilical vein endothelial cells were examined. Northern blot analysis of total RNA from endothelial cells demonstrated that interleukin (IL)-1 beta, IL-6, and colony-stimulating factor 1 (CSF-1) mRNA expression was absent or minimal in uninfected cells but significantly increased in infected cells. c-sis mRNA levels diminished with increased time of infection. In situ hybridization studies also demonstrated high levels of IL-6 mRNA in individual infected cells. Significant levels of IL-6 and IL-1 beta protein were detected in the supernatants of infected endothelial cells. The serum of an acutely infected individual contained high levels of IL-6 protein, suggesting the potential importance of cytokines secreted by the vascular endothelium in the pathogenesis of Chagas' cardiomyopathy. PMID- 1500743 TI - Monitoring of antibodies against human immunodeficiency virus type 1 p25 core protein as prognostic marker. AB - Anti-p25 antibodies were evaluated by cross-sectional analysis of sera from 130 human immunodeficiency virus type 1-infected patients and in a longitudinal study of 56 patients by retrospective analysis of sequentially collected sera. High and stable antibody levels were found in Centers for Disease Control stage II or III patients, 78% of whom had levels greater than 10 arbitrary units/mL. Patients with AIDS-related complex displayed heterogeneous levels. Patients with AIDS had the lowest values: less than or equal to 10 units/mL in 96% of cases. In patients whose CD4+ cell counts eventually fell below 200/mm3 or who developed AIDS (or both), antibodies were initially less than 40 units/mL and/or they declined with a rate greater than 1 log unit/5 years, beginning at least 4 years before the index symptom. Because the only point at which CD4+ cell counts significantly differed between progressors and nonprogressors was 1 year before the disease, both initial anti-p25 values and antibody decline seemed to be better long-term prognostic markers than CD4+ cell counts. PMID- 1500745 TI - Concordance of human immunodeficiency virus detection by polymerase chain reaction and by serologic assays in a Dutch cohort of seronegative homosexual men. AB - In three subgroups of a clinically and socially well defined group of Dutch homosexual men, the prevalence of human immunodeficiency virus type 1 (HIV-1) sequences in seronegative blood samples was studied using the polymerase chain reaction (PCR). In 19 seronegative partners of seropositive persons, no HIV-1 sequences were found by PCR in either early (1984/1985) or more recent (1987) samples. In 42 seronegative persons selected by their high risk for HIV-1 infection, none harbored HIV-1 sequences in either early (1985/1986) or late (1989) samples. In 15 people who seroconverted for HIV-1, only 2 samples collected 3 months before seroconversion were PCR-positive. These persons were also HIV antigen-positive at this time. These data suggest that a latent infection greater than 6 months does not occur and that the combination of HIV antibody and HIV antigen tests is appropriate and conclusive in most cases of HIV 1 infection. PMID- 1500744 TI - Early diagnosis of human immunodeficiency virus infection in children less than 6 months of age: comparison of polymerase chain reaction, culture, and plasma antigen capture techniques. AB - Three techniques were evaluated for their ability to detect human immunodeficiency virus (HIV) in infants from birth to 6 months of age. Polymerase chain reaction (PCR) and HIV cocultivation were of comparable sensitivity, detecting 90% of all positive specimens. Both techniques found positive results in approximately 5% of samples from seroreverting children. Both assays detected HIV in only half of infected newborns, suggesting that this fraction of children was infected during gestation. Plasma p24 antigen was detected in three-fourths of all samples tested but in only half of infected children during the first 2 months of life and 88% of samples from children during the next 4 months. The specificity of p24 antigen detection was 100%. PMID- 1500746 TI - Immunosuppression with cyclosporine during the incubation period of experimental woodchuck hepatitis virus infection increases the frequency of chronic infection in adult woodchucks. AB - The immunosuppressive agent cyclosporine was given to adult woodchucks during acute experimental infection with woodchuck hepatitis virus (WHV). All 17 woodchucks given WHV alone or with a vehicle resolved the infection (i.e., zero chronicity), but when cyclosporine was given throughout the incubation and acute phases of infection (0-12 or 14 weeks; n = 12), the rate of chronic infection increased to 92%. When cyclosporine was given only during the incubation period (0-4 weeks; n = 10) or only during the acute phase of infection (2-12 weeks; n = 9), the rates increased to 50% and 55%, respectively. However, when the drug was given after the acute phase (8-18 weeks; n = 9), the chronic infection rate (11%) did not differ from that in untreated and vehicle controls. Immune responses inhibited by cyclosporine are important in resolution of acute WHV infection and occur mainly during the first 8 weeks. Immunosuppression of these responses for even short intervals during incubation (e.g., 0-4 weeks) increases the risk of chronicity. PMID- 1500747 TI - Role of cell wall polysaccharide in the assessment of IgG antibodies to the capsular polysaccharides of Streptococcus pneumoniae in childhood. AB - The interference of antibodies to pneumococcal cell wall polysaccharide (CWPS) in the measurement of antibodies to capsular polysaccharides in children was assessed after vaccination with pneumococcal polysaccharide vaccine. ELISAs were developed to measure IgG subclasses specific for pneumococcal types 3, 6, 19, and 23 and CWPS. Analysis of antibody levels to all four capsular polysaccharides was affected by the presence of antibodies to CWPS, and their removal altered both anti-capsular polysaccharide antibody levels and the interpretation of responses to the vaccine. Thus, it is likely that CWPS contaminating pure capsular polysaccharide reagents used in most standard immunoassays is responsible for falsely elevated measurements of antibodies to capsular polysaccharide and the incorrect assessment of anti-pneumococcal antibody status in childhood. PMID- 1500748 TI - Neonatal mouse model of group B streptococcal infection. AB - Neonatal mice were infected with type III group B streptococcal (GBS) strain M781 by the intraperitoneal route. Age-related susceptibility to challenge was seen within the first 5 days of life. Quantitative blood cultures demonstrated a rapid increase in bacterial numbers during the first 30 h after challenge. Infected pups showed clinical signs of septicemia, and most succumbed within 48 h of challenge. Histopathologic evaluation of the neonates showed bacterial infection within 1 day after challenge. Pregnant adult mice were given a single inoculation of serum raised in rabbits against a tetanus toxoid-conjugated type III GBS polysaccharide vaccine. This serum passively protected 100% of the offspring. This neonatal mouse model of GBS infection and protection may be suitable for study of various forms of intervention. PMID- 1500749 TI - Salmonella typhimurium bacteremia: association with the virulence plasmid. AB - Virulence plasmids, which are found in a small number of Salmonella serotypes, greatly enhance the extraintestinal growth of salmonellae and lower the LD50 by 2 5 logs in experimental murine infections. To determine if virulence plasmids are important in the pathogenesis of Salmonella bacteremia in humans, blood and fecal isolates of Salmonella typhimurium from California were examined for the presence of a virulence plasmid. Colony blots were done using a labeled probe made from the highly conserved EcoRI fragment of the Salmonella dublin virulence plasmid. A total of 42% of the fecal and 76% of the blood isolates hybridized with the probe. This is the first evidence that the virulence plasmid is important in the pathogenesis of Salmonella bacteremia in humans. PMID- 1500750 TI - Anti-tetanus toxoid antibodies in intravenous gamma globulin: an alternative to tetanus immune globulin. AB - The levels of anti-tetanus toxoid IgG antibodies were measured in 29 lots of intravenous gamma globulin (IVIG). The antibody levels varied from 4 to 90 IU/mL (geometric mean, 18.6; 90% confidence interval, 9.7-35.7). The variation from manufacturer to manufacturer accounted for most of the observed differences among lots; there was relatively little variability among multiple lots from a single manufacturer. IVIG may be an acceptable alternative to horse or human tetanus immune globulin. PMID- 1500751 TI - Seroepidemiology of Chlamydia pneumoniae TWAR infection in Seattle families, 1966 1979. AB - Incidence rates of Chlamydia pneumoniae infection and information on reinfection and transmission within families were obtained by serologic study of serum samples from prospective family studies conducted 1966-1979. Specimens (n = 3671) from 343 subjects in 68 families were tested for TWAR antibody using the microimmunofluorescence assay. Acute infection was defined as a fourfold rise in antibody titer between consecutive specimens. Sixty-four episodes of infection were identified in 58 persons; 4 had 2 infections and 1 had 3. From late 1975 until early 1979, when 3 serum specimens were collected yearly, rates of infection by age groups 0-4, 5-9, 10-14, 15-19, and greater than or equal to 20 years were 0, 9.2, 6.2, 2.2, and 1.5/100 person-years, respectively. Reinfections, defined as infections in persons with previous antibody, constituted most acute infections among adults. Acute infections more often affected a single family member than multiple members, but 2 or 3 family members were infected during the same period 12 times. PMID- 1500752 TI - Compartmentalization of lipopolysaccharide production correlates with clinical presentation in meningococcal disease. AB - Lipopolysaccharide (LPS, endotoxin) was quantified in plasma and cerebrospinal fluid (CSF) collected simultaneously from patients with systemic meningococcal disease. High levels (median, 3800 ng/L; range, 750-14,000) were present in plasma and low levels (median, 40 ng/L; range, less than 25-165) in CSF of patients with fulminant septicemia. Conversely, high levels (median, 2500 ng/L; range, less than 25-500,000) in CSF and low or undetectable levels (median, less than 25 ng/L; range, less than 25-210) in plasma were associated with meningitis without septic shock. Levels of LPS were significantly correlated with protein levels in CSF (r = .50, P = .01) and inversely correlated with the ratio of glucose in CSF to that in blood (r = -.62, P = .0005). LPS level in CSF greater than 800 ng/L was significantly associated with greater than or equal to 10(9) leukocytes/L, protein levels greater than 0.5 g/L, and a glucose ratio less than 0.5. Thus, quantification of LPS levels in the plasma and CSF in systemic meningococcal disease is a better predictor of pathophysiologic events than is demonstrating the presence of live bacteria as in conventional culture. PMID- 1500753 TI - Comparison of urine and serum concentrations of interleukin-6 in women with acute pyelonephritis or asymptomatic bacteriuria. AB - The mucosal and systemic interleukin-6 (IL-6) response to urinary tract infection was analyzed in women with acute pyelonephritis or asymptomatic bacteriuria. Urine and serum samples were obtained at diagnosis and after treatment. IL-6 activity was elevated in urine samples from most bacteriuric women, regardless of the severity of infection. Urinary levels greater than 20 units/mL occurred in 25 of 29 women with acute pyelonephritis and in 36 of 42 women with asymptomatic bacteriuria. Elevated serum IL-6 levels were found mainly in patients with acute pyelonephritis: Levels greater than 20 units/mL occurred in 14 of 28 women with acute pyelonephritis compared with 0 of 28 women with asymptomatic bacteriuria. These results suggest that bacteriuria is accompanied by elevated urinary IL-6 levels and that this IL-6 is locally produced. The spread of IL-6 to the circulation in patients with acute pyelonephritis may contribute to the elevation of fever and C-reactive protein characteristic of the disease. PMID- 1500754 TI - Absence of intrathecal synthesis of some interferon-alpha subtypes in bacterial meningitis. AB - Sixty-five cerebrospinal fluid (CSF) samples from 54 infants and children with bacterial meningitis were analyzed for the presence of interferon (IFN)-alpha with a biologic assay. Of the 65 samples, 3 were positive (2-4 IU/mL) and only 1 of 56 collected early was at 4 IU/mL. These results suggest that some subtypes of IFN-alpha already reported as present in viral infections of the central nervous system are not detected in bacterial meningitis by our IFN assay. This difference may be helpful in differentiating bacterial from viral infections and also in evaluating the quality of the virologic investigation; moreover, the rarity of IFN-gamma in CSF in bacterial meningitis needs further investigation to understand its role in the pathogenesis of the disease. PMID- 1500755 TI - Diagnosis of Mediterranean spotted fever by indirect immunofluorescence of Rickettsia conorii in circulating endothelial cells isolated with monoclonal antibody-coated immunomagnetic beads. AB - Rickettsia conorii, an obligate intracellular bacterium that infects vascular endothelial cells, is the etiologic agent of Mediterranean spotted fever (MSF). A new procedure using indirect immunofluorescence was used to directly detect R. conorii in circulating endothelial cells (CEC). CEC were separated from other blood components by using anti-endothelial cell monoclonal antibody-coated magnetic beads. An anti-R. conorii polyclonal rabbit antiserum was used to stain rickettsiae. The entire procedure took 3 h. R. conorii was detected in CEC from 9 of 12 patients ultimately confirmed as having MSF. Among the patients, 5 with R. conorii isolated by centrifugation-shell vial assay were also positive by the new technique. None of 3 patients whose diagnosis was other than MSF had R. conorii detected in CEC. The procedure may be helpful for rapid diagnosis of MSF and may lead to new technical approaches for the diagnosis of infectious diseases caused by intracellular pathogenic microorganisms. PMID- 1500756 TI - Cytokine-induced human multinucleated giant cells have enhanced candidacidal activity and oxidative capacity compared with macrophages. AB - The granulomatous response to infection is characterized by formation of multinucleated giant cells (MGC). A model has been developed for the study of MGC using fresh human peripheral blood monocytes cultured in medium supplemented with autologous serum and a combination of recombinant human interferon-gamma and interleukin-3 (100 units/mL each). Differential Giemsa staining demonstrated a 53% increase in candidacidal activity of MGC (35.1% +/- 2.0% of ingested organisms were killed by MGC) compared with identically cultured mononuclear macrophages (which killed 22.9% +/- 1.8% of organisms ingested; P less than .05). There was no significant difference in the number of organisms ingested. MGC stimulated with phorbol myristate acetate produced 2.2 times as much superoxide anion per unit of cytoplasmic protein as identically cultured and stimulated macrophages (34.3 vs. 16.2 nmol of superoxide/microgram of cell protein; P less than .01). This was corroborated with single-cell measurements of oxidative activity using digital image analysis. These observations support the hypothesis that MGC have an advantage in microbicidal activity over macrophages that may be due, at least in part, to enhanced oxidative capacity. PMID- 1500757 TI - Restaurant-associated outbreak of giardiasis. AB - An outbreak of giardiasis occurred among staff of a job training center after a meeting at a restaurant. Twenty-seven (75%) of 36 attendees became ill compared with 1 (3%) of 31 staff members not attending (relative risk, 23.3; 95% confidence interval, 3.4-161.4). Because most attendees ate all items on a fixed menu, no individual food item could be conclusively associated with illness. Circumstantial evidence suggests, however, that ice contaminated by a food handler may have been the vehicle. The restaurant had multiple sanitary violations, and 2 employees, 1 with asymptomatic giardiasis and the other with a Giardia-infected, diapered child, served ice to the attendees. This outbreak demonstrates the potential for restaurant-based giardiasis outbreaks. PMID- 1500758 TI - Detoxification of meningococcal endotoxin by polymyxin B. PMID- 1500759 TI - Knowledge of therapeutics for human immunodeficiency virus infection among intravenous drug users. PMID- 1500760 TI - Interferon-gamma treatment for Mycobacterium avium-intracellular complex bacillemia in patients with AIDS. PMID- 1500761 TI - Pharmacokinetics of zidovudine plus probenecid. PMID- 1500762 TI - Role of clindamycin with or without another agent for treatment of pneumocystosis in patients with AIDS. PMID- 1500763 TI - Splenic echinococcosis: clinical and serologic evaluation. PMID- 1500764 TI - Fine structure of spermiogenesis in the coccid insect Aspidiotus perniciosus: late stages of differentiation and structure of the mature sperm bundles. AB - Spermatids of A. perniciousus are organized into bundles each containing 32 cells. During the process of differentiation, nuclear elongation and chromatin condensation take place. The mature sperm bundles are finally surrounded by the secondary sheath which is composed of a trilaminar membrane. The mature sperm is not differentiated into head, mid piece or tail but has two tapering ends and an electron dense central core. Centrioles, the nuclear membrane, mitochondria and a flagellum appear to be lacking. Microtubules are arranged in a spiral pattern forming the enveloping microtubular sheath. PMID- 1500765 TI - Ultrastructure of symbiont-like microorganisms associated with the sperm of ixodid ticks. AB - The endospermatophores found in the seminal receptacles of three species of Ixodid ticks: Hyalomma marginatum, H. dromedarii and Amblyomma hebraeum were examined. The seminal receptacles showed the presence of symbiont-like microorganisms in association with the sperm cells. These yeast-like microorganisms represent extracellular symbionts, produced by the male and introduced in the genital system of the female through copulation. The symbionts frequently occur freely in large agglomerations surrounded by a large amount of alpha-glycogen rosettes. They do not alter their shape nor do they attach to the sperm cells. Another kind of Rickettsia-like microorganisms is present in tissues of some tick organs. This could be a form of disease agents or naturally occurring microorganisms in the tissue of tick organs. PMID- 1500766 TI - Intestinal parasitic infection among sewage workers in Alexandria, Egypt. AB - This research was conducted to study the risk of intestinal parasitic infections among sewage workers. A hundred sewage workers in Alexandria and another hundred as control group not exposed to sewage were selected for this research. The results indicated that sewage workers were at a higher risk of developing intestinal parasitic infection especially Ascariasis and Amoebiasis. Nail examination revealed that sewage workers were at a higher risk of infection by Entrobius vermicularis. PMID- 1500768 TI - Cutaneous leishmaniasis in outpatients of dermatology and venereology clinic, Benha Faculty of Medicine, Zagazig University, Egypt. AB - Zoonotic cutaneous leishmaniasis (ZCL) is a disease of an ancient history and more or less encountered in several Egyptian Governorates. However, no data is available concerning CL. in Qualyobia Governorate. In the present study, a number of 10920 patients who attended the outpatient's clinic of Dermatology and Venereology, during the year 1991, were clinically examined for any manifestations suggesting CL. Lesion when present was examined by Giemsa stained smear and N.N.N. medium culture. Serum samples were separated from blood of suspected CL. cases for detection of antileishmanial antibodies by the indirect haemagglutination tests. The results showed that six patients had parasitologically proven lesions and that IHAT was less specific in diagnosing CL. It was concluded that CL exists as endogenous cases in Qualyobia Governorate and that the presence of CL and VL within nearly the same focus is a point of medical importance. PMID- 1500767 TI - Profile of portal hypertension in hepatosplenic schistosomiasis. AB - Intrasplenic pressure changes versus ova count in stool of schistosomal portal hypertension in cases of bilharzial hepatic fibrosis were studied before and after 40 mg/kg body weight praziquantel therapy. Praziquantel acts on the vascular level in which it decreases the portal hypertension caused by bilharziasis as detected by decreased size of portal and splenic veins diameter as well as a significant decrease of portal pressure by the decrease of intrasplenic pressure (P less than 0.05). On the other hand, praziquantel decrease bilharzial stool egg count after 3 months of therapy (P less than 0.05). PMID- 1500769 TI - Alternate chemotherapy in experimental schistosomiasis. AB - Schistosoma mansoni infected mice were treated with a single oral dose of either praziquantel (400 mg/kg) or oxamniquine (100 mg/kg). The uncured mice, after the first dose, were given a second dose of the same drug or alternatively with the other drug. The drug efficacy was monitored by stool examination and egg count using Kato-thick smear technique. Praziquantel was found to be more effective, it gave 60% cure rate after the first dose, increased to 100% after the second dose, than oxamniquine which had 37% and 74% cure rates respectively. Furthermore, in uncured mice praziquantel resulted in more egg count reduction than oxamniquine. Treatment with the alternate drug of mice not cured with the first treatment gave 100% cure rate with praziquantel and 83% with oxamniquine. It was concluded that praziquantel is generally more effective than oxamniquine and cases not cured with a single dose of either drugs may be effectively treated with a second dose of the other. PMID- 1500770 TI - Effect of Crytocotyle lingua on the ionic concentration of Littorina obstusata (L.). AB - The concentration of Sodium, Potassium and Calcium ions (the most important inorganic ions in the body fluid) were determined in both parasitized and uninfected Littorina obtusata (L.). The ionic concentrations were determined using a Pye Unicam SP atomic absorption spectrophotometer. Sodium and calcium were determined using the absorption mode while, potassium concentration was measured in the emission mode using special Potassium filter. The results reveals, no significant difference in the concentration of Na+, K+ and Ca++ between parasitized and uninfected L. obtusata. It seems that although the presence of the parasite within the molluscan hosts caused dramatic effects in the tissue and physiology of the snail, the blood ionic concentration of parasitized snail remains isosmotic to that of the surrounding medium. PMID- 1500771 TI - Myopathic changes in schistosomal hepatosplenomegaly; histopathological, histochemical and immunopathological studies. AB - Eighteen patients suffering mainly from schistosomal hepatosplenomegaly (B.H.S.M.) were selected & classified into 3 groups according to the degree of B.H.S.M. Muscle biopsy for histopathological, histochemical and immunopathological studies were taken. The results showed that fatiguability as a symptom was present in all cases but motor weakness was present in four cases. Twelve cases had peripheral neuropathy in the form of glove and stocking hypothesia, while pyramidal tract lesion was present in four cases. Two cases, however, showed both peripheral neuropathy and pyramidal tract lesions. Histopathological and histochemical assessment revealed frank myopathic changes in 14 cases while only one case showed definite neuropathic changes. The remainder cases were inconclusive. Immunopathological examination revealed marked deposition of IgG in 50% of cases, while IgM and IgA showed mild to moderate reactions. It was concluded that muscular changes in schistosomal patients are myopathic in nature and that immunological mechanisms could be considered as a factor in the pathogenesis of this muscular disorder. PMID- 1500772 TI - The efficacy of IHAT, IFAT and Dot-ELISA in sero-diagnosis of toxoplasmosis in complicated pregnancies. AB - Studying of 72 pregnant women having congenital anomalies, stillbirth and repeated abortion of first and second trimesters showed Toxoplasma antibodies with high titre by IFAT and Dot-ELISA. Analysis of the results showed a positive correlation between IFAT and Dot-ELISA but not with IHAT. However, Dot-ELISA is simple, sensitive and specific. PMID- 1500773 TI - Scanning electron microscopy of the small intestine of rats experimentally infected with Cynodiplostomum azimi. AB - Scanning electron micrographs of the proximal intestine of rats infected with C. azimi showed mild villous changes and excessive mucus secretion as early as the first day after infection. On the second day the regular leaf-like pattern of the villi was not seen, the epithelial lining of the mucosa was damaged with large amounts of mucus. Goblet cell openings appeared either empty or filled with secretions. The mucosal damage persisted for three months. Four months after infection, villi regained part of their normal pattern. Their epithelial lining although less damaged, appeared delicate. Villi away from the worm were less affected. Pathological changes at different intervals of infection were discussed in relation to the surface structure of the parasite. PMID- 1500774 TI - Leishmania infection sought in rodents in north Sinai, Egypt. AB - Zoonotic cutaneous leishmaniasis (ZCL) is endemic in certain foci in North Sinai. In the present study, eight species of commensal and wild rodents were trapped from seven areas. Suggestive ZCL lesions were seen on R. rattus, R. norvegicus, G. pyramidum, G. ander soni, G. gerbillus and Meriones sacramenti. Positive Giemsa stained smears were identified in G. pyramidum. The results were discussed. It was concluded that the ZCL transmission cycle, animal reservoirs, sand fly vector and man, is documented. PMID- 1500776 TI - A freeze etching study on the distribution of nuclear pores during spermatogenesis in ticks. AB - In this study the freeze-fracturing and freeze-etching techniques was used to study pore distribution during spermatogenesis in ticks. Three species of Ixodid ticks were studied: Hyalomma dromedarii, H. marginatum and Amblyomma hebraeum. In all three species of the ticks examined, the nuclei of the early stages of male germ cells showed varying degrees of aggregation into pore-rich and pore-poor areas. Spermatocytes demonstrated significant pore clustering in pore-rich areas, leaving areas almost devoid of pores. Spermatids on the other hand displayed a random distribution of nuclear pores. This random distribution was soon modified in the course of nuclear differentiation. Nuclear pores disappeared in the nuclei of mature spermatozoa of the ticks examined. PMID- 1500775 TI - Immune response of gametocytes of Plasmodium falciparum in exogenous cases in Dakahlia Governorate, Egypt. AB - Following chloroquine treatment gametocytes numbers fell with a constant rate of loss over a period from 15-21 days. The gametocytes had a half-life of 2-4 days. The sex ratio was constant 4 female: 1 male. Antibodies to the gametocytes were detected in some patients. It was concluded that the gametocytes of P. falciparum are long-lived and can stimulate antibody production but the immune response appears to play no part in their elimination, which probably takes place in the spleen as a part of the normal process of removing old, damaged and malformed red cells. PMID- 1500777 TI - Tonsilar toxoplasmosis. AB - One hundred cases were suffering from chronic tonsillitis, aged between 4-12 years, of both sexes (60 males and 40 females), from outpatient clinic of E.N.T. unit at Benha Faculty of Medicine. They were examined serologically by indirect haemagglutination--antibody technique (IHAT) for toxoplasmosis. After tonsillectomy, histopathological and electronmicroscopical studies were done. Ten percent of cases were positive serologically, among males (11.71%) and females (7.5%). The positivity rate was high among age group 10-12 years than others. Two cases showed histopathological and ultrastructural changes indicating toxoplasmosis. PMID- 1500778 TI - Heterophyids: experimental chemotherapy and immunotherapy. AB - Heavy infections with the tiny flukes heterophyids can cause intestinal pain and mucous diarrhea, thus the study of praziquantel (Pzq) and the new drug cyclosporin A (CsA) as antiparasitic drugs were undertaken in this work, as well as the effect of matecercarial and adult antigens as immunizing agents. To assess the result of our work, the number and length of the recovered heterophyids were studied. Description of the surface by SEM was carried out for the groups: treated by cyclosporin A and immunized by adult heterophyid antigen (third fraction) which gave the highest percentage reduction. PMID- 1500779 TI - A contribution to the anatomy and histology of the female reproductive system of Amblyomma cajennense (Acarina: Ixodidae). AB - The genital system of the tick Amblyomma cajennense is composed of several parts: a single tubular ovary where a great number of ova develop except for a longitudinal groove on its dorsal surface, with feeding the ova develop multiplying the size and weight of the ovary, as they reach maturity they are ovulated into the lumen. Two oviducts are connected to the ovary on each side, these thicken at a certain region forming the knee shaped ampulla. This significant region is where great numbers of mature spermatozoa are found. The vagina is composed of a vestibular and a cervical part and leads to the exterior by the genital aperture. A large seminal receptacle opens into the cervical vagina, the function of the receptable is to receive and store endospermatophores. PMID- 1500780 TI - A general survey of ciliates associated with Periplaneta americana (L.) in the Central Region of Saudi Arabia. AB - The aim of this work is to identify and classify different species of ciliates which live in the alimentary canal of Periplaneta americana (L.) in the Central Region of Saudi Arabia. This insect was chosen because of the direct and indirect relationship to man. Identification of ciliates that live in the alimentary canal of this insect may be useful in the future for eradication of insects probably by making an epidemic among such insects. PMID- 1500781 TI - Seroepidemiology of Toxoplasma infection in Riyadh, Saudi Arabia. AB - A total of 362 apparently healthy Saudis of both sexes living in Riyadh and aged 4-60 years, were investigated for Toxoplasma antibodies using the indirect haemagglutination test (IHT). Eighty one (22.4%) were positive with titres of 1/64 or greater. A significantly higher prevalence of Toxoplasma antibodies was correlated with age and association with cats. Economic status showed an apparent, but not significant, negative correlation with antibody prevalence rates. No significant association was found between Toxoplasma infection and sex, consumption of raw or undercooked meat, and urban or rural residence. The results provide an evidence that cats may be the main source of human infection with Toxoplasma in Riyadh. PMID- 1500782 TI - Gastro-vascular and micro-vascular changes in chronic murine schistosomiasis mansoni-response to propranolol. AB - Histopathologic study of the gastric wall of mice infected with Schistosoma mansoni was carried out at 8, 12, 16 and 20 weeks post-infection (p.i.). The gastric vascular structures were more sensitive to injury with the progression of liver disease than the glandular cells, with marked submucosal edema and thickening of submucosal and subserosal vessels. By transmission electron microscopy, the mucosal microvessels had thickened basement membrane and conspicuous endothelial cells with granular cytoplasm thrown into numerous intraluminal microprojections and with increased number and size of pinocytotic vesicles. When propranolol was administered orally as 20 mg/kg daily doses for two weeks at 6, 10, 14 and 18 weeks p.i., a striking regression of gastro vascular and micro-vascular changes has been observed, particularly with early drug therapy. Based on the present study, it can be concluded that "structural autoregulation" of gastric vasculature to the emerging portal hypertension in chronic murine schistosomiasis mansoni, is a dynamic process that could be reversed by propranolol therapy. This response could, possibly, improve gastric mucosal perfusion and functional abnormalities which may predispose the gastric mucosa to severe damage or hemorrhage. PMID- 1500783 TI - Effect of Capillaria hepatica infection on Schistosoma mansoni challenge in mice. AB - The combined infection between Capillaria hepatica and Schistosoma mansoni was studied. The results of this work revealed that C. hepatica infection induced significant reduction of S. mansoni worm load in the two groups infected with C. hepatica and challenged with S. mansoni either during worm maturation period of C. hepatica, or at the time of presence of C. hepatica eggs in the liver Reduction in total and tissue egg count was also reported, but eggs excreted in the stool showed no difference in count from that of S. mansoni-infected controls. Oogram pattern of the experimental groups revealed a higher percentage of dead eggs and absence of mature and some developing stages. Scanning electron microscopy demonstrated severe destruction of adult worm of both groups. All these data showed the vigorous destructive effect of C. hepatica infection on the challenged S. mansoni. PMID- 1500784 TI - A brief note on phlebotomine sandflies in Riyadh, Saudi Arabia. AB - A total of 294 specimens were collected and identified as three species of the genus Phlebotomus and four species of the genus Sergentomyia. Of interest was the demonstration of promastigotes in the foregut of two females P. papatasi. PMID- 1500785 TI - Identification of the Schistosoma haematobium soluble egg antigens inducing antibody production and/or T cell proliferation in humans. AB - Soluble antigens were prepared from Schistosoma haematobium eggs collected from urine of 6-16 year-old children with urinary schistosomiasis. The electrophoretic profile of the soluble egg antigen (SEAH) preparation was almost identical to that (SEAh) obtained from UNDP/World Bank/WHO, Switzerland and prepared from S. haematobium eggs retrieved from intestines of infected hamsters. Reactivity of 50 individual patients with S. haematobium in Western blots led to the identification of the SEA protein bands carrying human B cell epitopes. Some, but not all, of these SEA proteins initiated peripheral blood T lymphocyte proliferation in T cell Western assays. These antigens are probably the ones inducing granulomatous response in vivo, and that are responsible for the immunopathology of the disease. PMID- 1500786 TI - Some ultrastructural studies on the excretory bladder of the adult Cynodiplostomum azimi (Trematoda: Digenea) in infected rats. AB - Transmission electron microscope was used to reveal the reserve bladder system of the adult Cynodiplostomum azimi in experimentally infected rats. It was shown that this system consisted of a number of lacunae. The lacunar lining appeared as syncytial epithelium containing many nuclei, mitochondria, dense secretory bodies, Golgi complex and bundles of smooth muscles. The outer surface of the excretory epithelium was highly folded and lamellated. These lamellae were continuous with the excretory epithelium. Small lipid droplets were observed within the excretory epithelium, while larger ones were associated with the lamellae. The large lipid droplets were released in the lacunal lumen after the rupture of the lamellae surrounding them. PMID- 1500788 TI - Ultrastructural aspects of intramolluscan developing cercariae of Echinostoma liei. AB - The ultrastructure of the daughter redia of Echinostoma liei inside their host Biomphalaria alexandrina is described. The tegument consists of one layer, bearing numerous microvilli on its outer surface. Besides, the description of the ultrastructure of the developing cercariae within the daughter rediae is also included in the present study. The young cercariae are covered with a thin nucleated primitive temporary epithelium, which is lost when the true tegument is formed beneath it. The mechanism of spine formation was not apparent, but there is some indication that the spines are associated with a thickened part of the basal membrane of the tegument. Section through these cercariae showed that the tissues lying below the tegument are disposed in consecutive layers, suggestively representing developing muscle tissues. PMID- 1500787 TI - Melanization response of two mosquito species against Wuchereria bancrofti. AB - The melanization response of two mosquito against Wuchereria bancrofti was studied under different conditions of temperatures, adult age and feeding regimes. The two mosquito species were Culex pipiens, a susceptible species for W. bancrofti transmission and Aedes Caspius, a refractory one. PMID- 1500789 TI - The effect of cyclosporin A (CSA) on murine visceral toxocariasis canis. AB - Swiss mice experimentally infected with T. canis were treated by Cyclosporin A (CSA). The direct antiparasitic effect was noticed when administered on the same day of infection and was more effective when repeated for eight weeks. Although immunosuppression of CSA increased the susceptibility of mice to T. canis larvae, its direct antiparasitic effect was more effective and led to diminution of living T. canis larvae. Cellular immunity was inhibited as revealed by diminution of T. lymphocytes by decreased lymphocytes migration inhibition percentage on repeated administration of CSA for four weeks. PMID- 1500790 TI - Cyclosporin A in experimental trichinosis: histopathological study. AB - Cyclosporin A (CsA), a relatively new drug, was previously used in a series of studies on experimental trichinosis. This work was conducted to study the histopathological changes of CsA treatment at different time intervals from T. spiralis infection in mice. The work included study of the effect of the drug on the larvae treated either in vivo or in vitro. The drug was most effective when it was administered on the same day of infection, then when given one week before. The effect was evidenced by diminution both in the number of larvae and in the cellular reactions. PMID- 1500791 TI - Evaluation of a direct agglutination test and methylene blue dye test in diagnosis of cutaneous leishmaniasis. AB - The usefulness and sensitivity of a direct agglutination test (DAT) in the diagnosis of cutaneous leishmaniasis infection has been investigated. Trypsin treated, formalin fixed and coomassie blue stained Leishmania promastigotes were used as antigens: L. infantum, L. donovani, L. aethiopica. Although the titres of sera from patients with localized cutaneous leishmaniasis were low, sera from lepromatous, tuberculous and toxoplasmic patients gave high titres indicating cross reactivity. Comparable results were obtained when the same sera were tested using freshly prepared antigen or antigens stored for 5 months at 4 degrees C, and with addition of 0.78% 2-mercaptoethanol to the diluent. PMID- 1500792 TI - Identification and characterization of specific hydatid antigen fraction(s). AB - A specific hydatid antigen was prepared in this study from Echinococcus granulosus cyst in livers and lungs of camels. Elimination of host "camel" protein from crude hydatid fluid was achieved by two methods: Salting out using ammonium sulfate precipitation method and immunoaffinity purification using coupled anticamel antibody to cyanogenbromide activated sepharose 4B gel. Testing the prepared hydatid antigen against anticamel serum, using immunodiffusion method, indicated that the affinity purified hydatid antigen was almost completely purified from camel protein. Characterization of the affinity purified hydatid antigen, using immunoelectrophoresis, showed positive arc 5 precipitation when tested against known positive antihydatid sera. Further characterization with gradient gel electrophoresis, showed with silver stain that the dominant and most consistently demonstrable proteins occurred as a complex in the 52/62 KDa region. Strong reaction with the 52/62 KDa complex was consistently observed when the affinity purified hydatid antigen was probed with known positive reference antihydatid sera. The identified hydatid antigen fraction(s) with 52/62 KDa complex can provide promising non-invasive parameter for diagnosis of Hydatidosis. PMID- 1500793 TI - Effect of larval population density on dynamics of growth in Chrysomyia albiceps (Wiedemann). I. Effect of feeding behaviour and growth rate of larvae. AB - The feeding behaviour of uncrowded and crowded larvae differed as soon as feeding began. In case of high density populations, larvae tend to form dense clusters and this gregariousness is responsible for much of the injury and resulting predation. Larval growth rate had the same pattern up to 200 larvae per 20 grams meat, then this pattern greatly changed with the increase of densities. Larval survivorship remained high at densities up to 160 larvae per 20 gm meat, then decreased rapidly as larval density increased. The duration of larval development was extended and synchronization of larval pupal ecdysis was affected. Percentage of pupation and pupal weight were greatly decreased at high densities. PMID- 1500794 TI - Lymphatic leishmaniasis. An adult case without visceral involvement from Sharkia Governorate, Egypt. AB - Lymphatic leishmaniasis was reported as an indigenous infection in a 30 year old male from Abo Hamad, Sharkia, Egypt. Cervical lymphadenopathy was the only clinical sign and no visceral involvement. Diagnosis was based on histopathological examination of needle biopsied material. The patient was successfully treated with sodium stibogluconate as shown clinically and parasitologically. It was concluded that lymphatic leishmaniasis should be in mind when dealing with lymphanopathy of unknown aetiology. PMID- 1500795 TI - Metabolic response in severely traumatized patients. AB - Acute severe trauma induces alterations in glucose, protein and fat metabolism through neurohormonal mechanisms. This study investigated the temporal relationship between serum cortisol, insulin levels and metabolic changes in glucose, protein and fat following acute severe trauma. Thirty adult patients admitted with polytrauma were investigated after two to three days of admission compared with thirty normal adults. There were highly significant increases in fasting blood glucose, ketones, triglycerides, cortisol and insulin, and highly significant decreases in total proteins and albumin. The study speculate that post traumatic hyperglycemia, decreased total proteins and albumin are major metabolic changes following severe trauma. These changes were mediated through neurohormonal mechanism included mainly the increased blood cortisol level. PMID- 1500796 TI - Schistosoma haematobium (Egyptian strain) transmission microscopy of normal and praziquantel treated worms. AB - The ultrastructure of the tegument and subtegumental structures of S. haematobium worms was examined by TEM. The effect of praziquantel on residual worms which remained after a curative dose was also studied. The male S. haematobium worms were characterized by deep tortuous pits and sharp apically directed spines. Spherical and elliptical bodies were also observed. The esophageal tegument was described. The effect of praziquantel on the male worms revealed flattening of spines and their disappearance in some regions as well as disruption and vacuolization of the tegument in others. PMID- 1500797 TI - Evaluation of adult Schistosoma mansoni and cercarial antigens in serodiagnosis of schistosomiasis using IHAT and ELISA. AB - Examination of 200 bilharzial cases divided into four groups and 50 normal controls to evaluate the efficiency of adult Schistosoma mansoni and cercarial antigens in serodiagnosis of schistosomiasis using IHAT and ELISA revealed that IHA test showed high sensitivity that decreased with the progress of clinical status of the disease if adult worm antigen was utilized. Also IHAT adult antigen was more sensitive for serodiagnosis than with cercarial antigen, while ELISA is less sensitive using both cercarial and adult antigens. PMID- 1500798 TI - Naturally occurring toxoplasma antibodies in serum and milk of lactating women. AB - Serum and milk of lactating women were tested for toxoplasmosis using specific IgG IFAT. Apparently healthy 70 women were selected: 54 from rural and 16 from urban areas. Serum and milk were simultaneously collected from each one. Sera were positive in 22 (31.4%) of the total 70; including 16 (29.6%) and 6 (37.5%) of rural and urban groups respectively. No statistical significant difference was found for positivity and titre levels between the two groups (P greater than 0.05). Milk was positive in 12 (17.1%) of the 70 women; including 10 (18.5%) and 2 (12.5%) from rural and urban groups respectively, having no statistical significant difference (P greater than 0.05). Comparing serum and milk for positivity and titre levels, also there was no statistical significant difference (P greater than 0.05). It is concluded that relatively low antibody levels in serum could be excreted in milk and may be protective for suckling babies. Occurrence of antibodies in serum and milk are homogeneously distributed between rural and urban inhabitants. PMID- 1500799 TI - Sampling genotypes on complex pedigrees with phenotypic constraints: the origin of the B allele among the Polar Eskimos. AB - Exact probability calculations are often infeasible on large complex pedigrees. Conditional independences, however, occurring as a natural consequence of Mendelian inheritance of genetic traits, define a locally dependent Markov random field on the state space of all genotypic configurations on the pedigree. The underlying Markov chain is irreducible for most traits determined by a diallelic locus. For a given pedigree and a known genetic model, the Gibbs sampler can be used to obtain good estimates of the posterior distribution of genotypes given the observed data. The areas of pedigree analysis to which such an approach would be most directly relevant include genetic counselling and selective animal breeding, together with questions about ancestral genotypes and the ancestral paths of rare alleles. The method is illustrated by tracing the ancestral paths of a rare allele in a simple diallelic system on a highly complex Eskimo pedigree. PMID- 1500800 TI - The dynamics and control of bovine tuberculosis in possums. AB - A model for the dynamics of an infectious disease in a wild animal population is analysed. The model incorporates susceptible, infected but not infectious, and infectious classes, with no recovery from disease, density-dependent regulation of host birth and death rates, and pseudo-vertical transmission. The existence and local stability of equilibrium levels are determined. Expressions for the intensity of three alternative control measures - the culling, sterilization, and vaccination of host animals - required to eradicate the disease are obtained. Finally, the model is applied to possible control measures against bovine tuberculosis infection in possums in New Zealand. PMID- 1500801 TI - The population dynamics of nematode infections of ruminants: the effect of seasonality in the free-living stages. AB - A previously published differential equation model for the dynamics of nematode infections of ruminants is modified to allow for time-dependent development and loss rates in the free-living stages. This converts the nonlinear autonomous system to one with periodic coefficients. Fourier transform methods are used to analyse the response of the modified system to these forced oscillations. For biologically reasonable parameter values, the annual pattern of parasitism is determined for the nonautonomous system, and compared with that for the autonomous system with periodic perturbations, and a system incorporating both effects. It is found that, whereas periodic perturbations due to management intervention determine the qualitative annual patterns of larval abundance and host infection, the seasonal dynamics of the larval stages change the magnitude of the adult worm burden. PMID- 1500802 TI - [Clinical significance of direct immunobead test to detect anti-sperm antibody]. AB - Direct immunobead test (IBT) (IgG.IgA) was carried out for 290 infertile men to detect antisperm antibodies. The results, compared with semen data analyzed by traditional methods and a computer assisted semen analyzer and with hormone levels, were as follows. 1) In 21(7.2%) out of the 290 men, IgG-immunobead (IB) binding was observed in more than 50% of their motile spermatozoa; in 10(3.4%) of the 290, IgA-IB binding. 2) In all of the cases with proven fertility, the IB binding rate was less than 60% for IgG-IB, and less than 40% for IgA-IB. This suggested that antibodies attached to sperm could be among the factors in male infertility. 3) Antibodies attached to the sperm head with binding rate of less than 40% were not considered to be a causative factor in male infertility. 4) The incidence of positive IgG-IB was higher, and also in each case the IgG-IB binding rate was higher than the IgA-IB. 5) IgG-IB binding parts of each spermatozoon included IgA-IB binding parts. 6) No significant relationship was observed between the results of traditional semen analysis, LH.FSH.PRL levels or PENETRAK and the rates of IB binding. PMID- 1500803 TI - [Evaluation of myometrial invasion in patients with endometrial cancer by magnetic resonance imaging]. AB - Magnetic Resonance Imaging (MRI) has been widely used for the diagnosis of gynecologic disease. We studied the clinical usefulness of MRI in 34 patients with endometrial cancer from July, 1988 to August, 1991. Pre-operative pelvic MRI was carried out to evaluate the myometrial invasion in these patients. MRI was accurate in predicting the presence or absence of myometrial invasion in 23 of 34 cases (68%), while echo or CT (computed tomography) was accurate in 26% and 8%. In conclusion, MRI is considered to be the most useful examination for the evaluation of myometrial invasion in endometrial cancer. PMID- 1500804 TI - [A group study on prognosis of ovarian cancer in Japan]. AB - An assessment has been made, with the cooperation of 22 institutes, of 1,185 cases of ovarian cancer as subjects who were treated in the period from January, 1980, to December, 1987. As a result, (1) As for distribution by clinical staging at the initial examination, the cases in Stage III were the most numerous, followed by those in Stage I, and if classified according to the histological type, serous cystadenocarcinoma was the most frequently observed in Stage III, and undifferentiated and unclassified carcinomata were observed in Stages III and IV. (2) In the examination of prognostic factors, it was confirmed that the clinical stage, histological type and diameter of the remaining tumor after the initial operation were important factors. (3) A significant difference was observed between the grade of histomorphological differentiation and prognosis, the difference was chiefly due to the deviated distribution of clinical staging in each group of differentiation. (4) A favorable trend was observed in the prognosis by patient's age toward the younger layer. (5) When the starting time of the therapy is considered, a trend toward improvement has been seen year by year, and it is considered that the beneficial effect of chemotherapy with CDDP contributes to this. PMID- 1500805 TI - [Effect of suppletory estrogen or 1,25(OH)D3 on bone mineral content]. AB - Post-menopausal changes in bone mineral content (BMC) and the effect of suppletory estrogen or 1,25(OH)D3 was studied. BMC was evaluated by means of quantitative computed tomography. Post-menopausal BMC (age 45-49) was 158.4 +/- 42.0 mg/cm3 which was significantly lower than in other subjects in the same aged group (192.3 +/- 27.1 mg/cm3). At two years, ten years and more than ten years post-menopause it decreased significantly by 17%, 30%, 55% respectively, compared with that of pre-menopausal BMC. The administration of conjugated estrogen (0.625 mg) or 1,25(OH)D3 was effective in preventing bone loss, although a transient decrease in BMC was observed in some cases to which 1,25(OH)D3 was administered. In cases of pre-menopausal bilateral oophorectomy, BMC was found to decrease significantly to the post-menopausal level about two years after operation. However, long-term estrogen replacement therapy tends to inhibit the decrease. PMID- 1500806 TI - [A trial of low-dose aspirin therapy in high-risk pregnancy]. AB - Intra-uterine growth retardation, intra-uterine fetal death and pre-eclampsia have common abnormalities: A reduction of uteroplacental perfusion, lack of vasodilation of spiral arteries and subsequent thrombosis. These physiological processes have been explained by an imbalance between prostacyclin and thromboxane A2 production. Many studies have suggested that treatment with low dose aspirin and steroids is effective in preventing pregnancy loss or pre eclampsia, but the mechanism has not been established. We evaluated the effectiveness of these therapies in patients at risk for pregnancy loss with the aspect of intracellular ionized calcium mobilization. Low-dose aspirin directs the prostacyclin/thromboxane A2 balance to the dominance of prostacyclin and steroids suppress the activities of lupus anticoagulant or antiphospholipid antibodies. The intracellular ionized calcium concentration in platelets is decreased significantly after these therapies. Concerning the pathological examination of placenta, there were deposits of fibrin in only 2 out of 8 cases and there were no abnormal findings in the other 6 cases. These data show that the aggregation of platelets is suppressed in microvascular circulations. These therapies do not cause any adverse effect on the mother or fetus. It is concluded that low-dose aspirin therapy with steroids is useful for patients with a poor obstetrical history. PMID- 1500807 TI - [Morphological investigation in microscopic mole]. AB - Although regulations for treating trophoblastic disease have been established, the diagnostic standards and biological behavior of the microscopic mole are not always described distinctly. I observed morphological changes in the various villi existing between abortion villi and normal villi or total mole and investigated problems related to the microscopic mole. As a result, (1) the disappearance of the villous vessels, central liquefaction and proliferation of the villous cells were observed, though at a low incidence, not only in patients with abortion but also in those with normal villi; (2) When the short axis of the villi was 1,000 microns or less, there were no patients in which villus vessels disappeared, or central liquefaction or proliferation of the villous cells occurred; (3) Among patients with villi having a short axis of 1,000 microns or more, there were patients in whom trophoblastic disease could not be completely distinguished from total mole. A successive tumor developed in 2 patients in the group with (3) findings; (4), I propose that patients who satisfy the criteria in (3), above, should be regarded as those with microscopic mole while others should be regarded as those with hydropic degeneration in a narrow sense. PMID- 1500808 TI - [A study on relationship between functional sterility and ultrasonographic endometrial images]. AB - By means of vaginal ultrasonography 38 cases with functional sterility were investigated. Ultrasonographic endometrial thickness and texture, along with the maximum follicle diameter, serum estradiol and progesterone levels were measured in connection with the outcome of treatment for sterility. Endometrial texture was classified into 4 types: even-hypoechoic (P1) and mixed (P2) in late proliferative and even-echogenic (S1) and mixed (S2) in mid-secretory phases. Histological findings were also compared with ultrasonographic images and the following results were obtained. 1. Endometrial thickness and outcome of sterility. 1) Endometrial thickness in mid-proliferative and mid-secretory phases was 9.7 +/- 1.4 mm (mean +/- SD) and 13.9 +/- 1.7, respectively, in a group with good prognosis, while it was 6.7 +/- 1.8 and 10.1 +/- 2.2 in a poor prognosis group. The endometrium was significantly thinner in the latter group than in the former (p less than 0.05). 2) No. difference was found in estradiol, progesterone levels or the maximum diameter of the follicle. 2. Endometrial texture and outcome of sterility. 1) The outcome was identical in both groups whether the endometrium in late proliferative phase was of the even-hypoechoic or of the mixed type. 2) In the mid-secretory phase, comparison of patients where endometrium was of the even-echogenic type (S1) with those who had the mixed type (S2), revealed clearly poorer prognosis in the latter (p less than 0.05). 3) Serum estrogen and progesterone levels were not significantly different in any endometrial patterns and no connection was found between endometrial textures and the hormonal levels. 3. Histological findings in cases where mixed pattern endometrium was observed.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1500809 TI - [A new method of sperm selection by an affinity column using the pisum sativum agglutinin for the perivitelline injection of sperm]. PMID- 1500810 TI - [Serous surface papillary carcinoma of the peritoneum: a case report]. PMID- 1500811 TI - [A case of twin pregnancy associated with transient diabetes insipidus]. PMID- 1500812 TI - [Antenatal diagnosis of hydrocolpos]. PMID- 1500813 TI - [A case of malignant struma ovarii with rib metastasis]. PMID- 1500814 TI - TNF and IL-1 in sepsis: good cytokines gone bad. PMID- 1500815 TI - Mononuclear cells, platelet-derived growth factor, and IgA nephropathy: what does it mean? PMID- 1500816 TI - Scratching the surface: endothelium as a regulator of thrombosis, fibrinolysis, and inflammation. PMID- 1500817 TI - Nitric oxide gas: mediator, modulator, and pathophysiologic entity. PMID- 1500818 TI - A role for inducible nitric oxide biosynthesis in the liver in inflammation and in the allogeneic immune response. PMID- 1500819 TI - Consequences of the interaction of platelet membrane glycoprotein GPIIb-IIIa (alpha IIb beta 3) and its ligands. PMID- 1500820 TI - Lipopolysaccharide, tumor necrosis factor, and interleukin-1 interact to cause hypotension. AB - Lipopolysaccharide (LPS) causes the syndrome of septic shock by initiating the release of endogenous mediators such as tumor necrosis factor (TNF) and interleukin-1 (IL-1) from macrophages. Hypotension is one of the important clinical features of septic shock; however, TNF is only hypotensive in high doses. Therefore we have investigated the interactions of low, nonhypotensive doses of LPS, IL-1, and TNF in the restrained unanesthetized rabbit. Combinations of nonhypotensive doses of TNF, IL-1, and LPS produced significant (p less than 0.05) decreases in blood pressure as compared with doses of each of the substances alone. TNF bioactivity in animals that were made hypotensive with combinations of TNF, IL-1, and LPS was lower than in animals that were made hypotensive with TNF alone. This suggests that TNF release that is stimulated by LPS is not the sole cause of the hypotension that is seen in this model of endotoxic shock. In this model, interactions of LPS, IL-1, and TNF occur and may explain hypotension during some episodes of sepsis. PMID- 1500821 TI - Activated peripheral blood mononuclear cells in IgA nephropathy express platelet derived growth factor B-chain messenger RNA. AB - We investigated platelet-derived growth factor (PDGF) A- and B-chain messenger RNA expression in peripheral blood mononuclear cells or T cells obtained from 26 patients with IgA nephropathy and 15 healthy age-matched control subjects. Most patients with IgAN (88%) showed elevated PDGF B-chain expression in peripheral blood mononuclear cells; no PDGF B-chain expression was detected in peripheral blood mononuclear cells of normal control subjects. In T cells from both patients with IgAN and normal control subjects, however, PDGF B-chain messenger RNA expression was not detected. A positive correlation was noted between PDGF B chain messenger RNA levels and urinary protein excretion. The PDGF B-chain messenger RNA expression in peripheral blood mononuclear cells also correlated with histopathologic changes in renal tissue obtained from patients with IgAN. Sixty-five percent of patients with grade III or IV histopathologic findings showed strong PDGF B-chain gene expression in their peripheral blood mononuclear cells. We could not detect PDGF A-chain messenger RNA expression in either peripheral blood mononuclear cells and T cells obtained from patients with IgAN and from healthy control subjects. These studies suggest that abnormally regulated PDGF B-chain expression in peripheral blood mononuclear cells may be associated with the progression of IgAN and may be useful as an indicator of disease activity. PMID- 1500822 TI - Thrombin induction of plasminogen activator inhibitor mRNA in human umbilical vein endothelial cells in culture. AB - We have previously reported that incubation of human umbilical vein endothelial cells (HUVECs) with human alpha-thrombin causes a time- and concentration dependent increase in secreted plasminogen activator inhibitor type 1 (PAI-1) activity (Gelehrter TD, Sznycer-Laszuk R. J Clin Invest 1986;77:165-9). Here we report that the regulation of PAI-1 activity by thrombin is secondary to the thrombin-induced increase in PAI-1 mRNA accumulation. Incubation of HUVECs for 6 to 24 hours with 0.3 to 1.0 U/ml thrombin causes a 1.8-fold to 10-fold increase in PAI-1 activity and a 1.5-fold to threefold increase in accumulation of both the 3.2 and the 2.2 kilobase PAI-1 mRNAs. These effects are prevented by the prior addition of hirudin, a specific thrombin inhibitor. Inhibition of RNA synthesis with actinomycin D blocks the thrombin induction of PAI-1 mRNA accumulation. The protein synthesis inhibitor, cycloheximide, which itself markedly stimulates the accumulation of PAI-1, appears to prevent the induction by thrombin, suggesting that thrombin may act by inducing another effector such as interleukin-1. Consistent with this hypothesis is our observation that simultaneous addition of antibodies to interleukin-1-alpha prevents the thrombin induction of PAI-1 activity and mRNA. PMID- 1500823 TI - The role of cytokines in polymyositis: interferon-gamma induces class II and enhances class I major histocompatibility complex antigen expression on cultured human muscle cells. AB - Aberrant expression of class II major histocompatibility complex molecules has been found on target cells of various autoimmune diseases, including muscle fibers in patients with polymyositis-dermatomyositis. In this study the effects of a number of recombinant human cytokines, individually and in combination, on class I and class II molecule expression by cultured human muscle cells were examined with monoclonal antibodies and an immunoperoxidase technique. The following cytokines were tested: interferon-gamma, tumor necrosis factor-alpha, tumor necrosis factor-beta, interleukin-2, interleukin-1 alpha and interleukin-1 beta. Only IFN-gamma induced expression of class II molecules in muscle cells. It also enhanced the preexisting class I molecule expression by muscle cells. These findings suggest that IFN-gamma is involved in the aberrant expression of major histocompatibility complex molecules in the affected muscles of patients with polymyositis-dermatomyositis. PMID- 1500824 TI - Surfactant protein A in bronchoalveolar lavage fluid. AB - We measured surfactant protein A and phosphatidylcholine in the bronchoalveolar lavage fluid from healthy volunteers and several groups of patients with lung diseases to obtain information on surfactant in the lung. We developed three types of enzyme-linked immunosorbent assays that used combinations of polyclonal antiserum and monoclonal antibodies. Phosphatidylcholine was assessed by enzymatic measurement. The median amounts of surfactant protein A in bronchoalveolar lavage fluid determined by the enzyme-linked immunosorbent assay with monoclonal antibodies were as follows: control subjects (n = 10), 2.82 mg/L (range, 0.92 to 5.17 mg/L); patients with asthma (n = 13), 1.89 mg/L (range, 0.45 to 2.95 mg/L); and patients with pulmonary sarcoidosis (n = 20), 2.98 mg/L (range, 0.68 to 7.02 mg/L). The median phosphatidylcholine concentrations in the bronchoalveolar lavage fluid were as follows: control subjects (n = 10), 20 mumol/L (range, 3 to 37 mumol/L); patients with asthma (n = 12), 24 mumol/L (range, 3 to 55 mumol/L); and patients with pulmonary sarcoidosis (n = 20), 26 mumol/L (range, 4 to 76 mumol/L). As a group, the patients with asthma had less surfactant protein A in bronchoalveolar lavage fluid than did the control subjects (Mann-Whitney U test, p less than 0.05). The surfactant protein A levels measured by the enzyme-linked immunosorbent assay with polyclonal antiserum and by a competitive enzyme-linked immunosorbent assay were also lower in bronchoalveolar lavage fluid from patients with asthma than in that from control subjects. The phosphatidylcholine concentrations in all groups were similar.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1500825 TI - Quantitative determination of porphyrins in rat and human urine and evaluation of urinary porphyrin profiles during mercury and lead exposures. AB - Measurement of urinary porphyrin excretion patterns (porphyrin profiles) is useful in the diagnosis and evaluation of diseases and disorders of porphyrin metabolism. However, experimental investigation of such disorders with rodent models has been hampered by the lack of an efficient procedure for the isolation and quantitative evaluation of porphyrins in rodent urine. This article describes an analytic procedure that overcomes the principal difficulties encountered with determination of porphyrins in rodent urine, including the loss of porphyrins during their isolation and interference of porphyrin fluorescence by contaminating materials. The procedure entails application of an acidified urine sample to a preconditioned C-18 preparatory column, preferential separation of essentially all potentially interfering contaminants by sequential phosphate methanol elution, and selective isolation of porphyrins, which are then separated and quantitated by high-performance liquid chromatography and spectrofluorometric techniques. This method has been used to characterize urinary porphyrin excretion patterns in male rats and to define the distinctive changes in porphyrin profiles associated with prolonged exposure to porphyrinogenic metals. The porphyrin excretion patterns of male and female human subjects are also described. This method is applicable to the investigation of urinary porphyrin profile changes associated with exposure to a wide range of porphyrinogenic chemicals in both animals and human subjects. PMID- 1500826 TI - Dimethyl sulfoxide decreases lung neutrophil sequestration and lung leak. AB - To investigate basic mechanisms of acute edematous lung injury (adult respiratory distress syndrome), the formylated tripeptide formyl-norleucyl-leucyl phenylalanine (FNLP) was instilled intratracheally into hamsters. Intratracheal FNLP produced time-dependent and dose-dependent increases in neutrophils recoverable by lung lavage (neutrophil alveolitis) and leak of intravenously injected albumin into the extravascular lung space (lung leak). Treatment with dimethyl sulfoxide (DMSO) decreased (p less than 0.05) neutrophil alveolitis and lung leak in hamsters given FNLP intratracheally. The effect of DMSO on various neutrophil functions was also studied in vitro. Addition of DMSO at concentrations (about 0.20%) measured in plasma of hamsters given DMSO decreased (p less than 0.05) neutrophil chemotaxis but not neutrophil superoxide anion generation or adherence to cultured endothelial cell monolayers or nylon fiber in vitro. We conclude that intratracheal FNLP causes neutrophil alveolitis and lung leak and that DMSO treatment ameliorates these processes, possibly by inhibiting neutrophil chemotaxis. PMID- 1500827 TI - Plasma histamine but not anaphylatoxin levels correlate with generalized urticaria from infusions of anti-lymphocyte monoclonal antibodies. AB - Anti-lymphocyte monoclonal antibodies have shown promise in trials for therapy of lymphocyte malignancies but are associated with a high frequency of immediate type anaphylactoid reactions. We have previously demonstrated that these immediate-type anaphylactoid reactions are not mediated by immunoglobulin E to anti-lymphocyte monoclonal antibodies. To gain insight into the mechanisms of these immediate-type anaphylactoid reactions, we measured plasma levels of histamine and anaphylatoxins (C3a, C4a, C5a) during 11 infusions in eight patients who received anti-lymphocyte monoclonal antibodies (T101 and Lym-1). Three patients experienced generalized urticaria (two with severe angioedema); a fourth patient had three isolated hives but without generalized manifestations of an immediate-type anaphylactoid reaction. Plasma histamine levels after infusions that were associated with generalized urticaria were significantly higher than those during infusions that were not associated with generalized urticaria (mean, 3.47 vs 0.18 ng/ml, p less than 0.001). Increases in C3a and C4a levels were observed after some infusions, but these did not correlate with generalized urticaria. Measurable rises in plasma C5a levels after infusions were not detected. Although these data should be viewed as preliminary considering the limited number of patients studied, the observed histamine release demonstrates that mast cell or basophil activation that is not mediated by immunoglobulin E to anti-lymphocyte monoclonal antibodies occurs in the pathogenesis of immediate type anaphylactoid reactions from anti-lymphocyte monoclonal antibodies. Although activation of the classical complement pathway may occur in some anti-lymphocyte monoclonal antibody infusions, this does not appear to explain immediate-type anaphylactoid reactions.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1500828 TI - Effects of probucol in renal function and structure in rats with subtotal kidney ablation. AB - Probucol is a bisphenolic compound that lowers serum cholesterol and also has potent antioxidant properties. The present studies examined the effects of probucol administration on renal function and structure in a rat model of subtotal renal ablation. After subtotal nephrectomy, rats were fed an isocaloric rat chow diet containing 22.8% protein with or without the addition of 1% probucol. After 4 weeks, clearance studies were performed for determination of glomerular filtration rate (inulin clearance) and effective renal plasma flow (paraaminohippurate clearance). After completion of clearance studies and measurements of arterial blood pressure, the animals were exsanguinated and renal tissue was obtained for histologic evaluation. There were no differences in body weight, hematocrit, and blood pressure between the two groups of rats 4 weeks after subtotal nephrectomy. Rats with a remnant kidney given probucol had a significantly lower serum cholesterol level (47.4 +/- 5.3 mg/dl vs 87.2 +/- 10.4 mg/dl) and urea nitrogen level (40.7 +/- 3.2 mg/dl vs 63.6 +/- 8.1 mg/dl) than the control group. Rats given probucol also had significantly greater values for inulin clearance and clearance of paraaminohippurate and significantly less proteinuria than control rats. Also, rats with a remnant kidney given probucol had a significantly greater number of normal glomeruli (6.2% +/- 2.1% vs 1.1% +/- 0.9%) and a lesser number of severely affected glomeruli, grades III and IV (26.0% +/- 5.9% vs 50.9% +/- 9.1%) than rats with a remnant kidney not given probucol. Tubulointerstitial changes also were significantly less in rats with a remnant kidney given probucol.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1500829 TI - Microplate and dot immunoassays for the serodiagnosis of tuberculosis. AB - A simple dot enzyme immunoassay based on the recognition of serum IgG antibody to a 30,000 dalton native antigen purified from culture filtrates of Mycobacterium tuberculosis was developed and compared with a standard plate enzyme-linked immunosorbent assay in the serodiagnosis of tuberculosis. The previously described favorable test characteristics of plate enzyme-linked immunoassay were confirmed; although the dot enzyme immunoassay was promising, it was less satisfactory. Dot enzyme immunoassay may have its most promising use as a screening test for situations of limited technical facilities. Both plate enzyme linked immunoassay and dot enzyme immunoassay had markedly reduced sensitivities in persons with human immunodeficiency virus infection. PMID- 1500830 TI - The effects of inhibition of plasma cholinesterase and hepatic microsomal enzyme activity on cocaine, benzoylecgonine, ecgonine methyl ester, and norcocaine blood levels in pigs. AB - We measured the blood levels of cocaine and its three major metabolites, benzoylecgonine, ecgonine methyl ester, and norcocaine, in three groups of male pigs weighing about 26 kg (25.75 +/- 0.25 kg) to determine the effects of inhibition of plasma cholinesterase and hepatic microsomal enzyme activity on cocaine metabolism. In addition, systemic elimination half-life, volume of distribution, and clearance of cocaine were calculated for the three groups. Group 1 pigs (n = 4) were pretreated with normal saline solution, group 2 pigs (n = 4) were pretreated with tetraisopropyl pyrophosphoramide, a specific plasma cholinesterase inhibitor, and group 3 pigs (n = 4) were pretreated with cimetidine, a hepatic microsomal enzyme inhibitor, all administered intramuscularly. Pigs were anesthetized with intravenous sodium thiopental; a carotid arterial cannula and an external jugular catheter were then inserted for the administration of cocaine and for blood sampling. Forty-five minutes later, when pigs were again completely awake, cocaine 3 mg/kg was given intravenously. Arterial blood samples were collected for the analysis of cocaine and cocaine metabolite levels just before and at 5, 10, 15, 30, 45, 60, 120, 180, and 1440 minutes after the administration of cocaine. Cocaine and cocaine metabolite blood levels were analyzed with high-pressure liquid chromatography methods and plasma cholinesterase activity was measured with a colorimetric method. The blood levels of cocaine and cocaine metabolites were significantly different among the three groups (p less than 0.05, analysis of variance). Statistically significant differences in half-life, volume of distribution and clearance were also seen among the three groups.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1500831 TI - IEC-18, a nontransformed small intestinal cell line for studying epithelial permeability. AB - Small intestinal epithelium is leaky and allows permeation of hydrophilic molecules of various sizes. Passively absorbed hydrophilic permeability probes have been shown to permeate across intestinal epithelium mainly through the paracellular pathways. In this study we introduce microporous filter-grown IEC-18 epithelial cells, a nontransformed small intestinal cell line, as a in vitro model of intestinal epithelium for the study of epithelial permeability. IEC-18 cells, originally derived from native rat ileal crypts, form confluent epithelium when grown on hydrated collagen-coated Millicell-CM permeable inserts (Millipore Corp., Bedford, Mass.). With scanning and transmission electron microscopy, the presence of tight junctions and desmosomes between cells and the development of microvilli at the apical surface were confirmed. Immunofluorescent labeling of ZO 1 proteins and desmoplakins verified the presence of tight-junctional proteins (ZO-1) and desmosomes in the intercellular junctions of confluent IEC-18 epithelium. The net electrical resistance of IEC-18 epithelium (28 omega-cm2) was similar to resistance values obtained from small intestinal tissue with (50 to 100 omega-cm2) or without (20 to 45 omega-cm2) muscularis and serosal layers. Assessment of mannitol and dextran permeation revealed early "maturation" of paracellular pathway, with increasing restriction of permeation to both probes through day 4. Resistance across IEC-18 epithelium also reached plateau levels between 4 and 7 days. Permeability studies with various probes indicate that cross-sectional diameter rather than molecular weight of the probe is the important determinant of permeation rate. IEC-18 epithelium selectively restricted the permeation of probes proportional to probe size; permeation of larger probes such as albumin was negligible. We conclude that cultured IEC-18 epithelial cells, because of their native crypt origin, similarity in resistance to small intestinal epithelia, retention of ability to differentiate into villus like enterocytes, and permeability characteristics, are a useful model of intestinal epithelium for the study of permeability and paracellular transport. PMID- 1500832 TI - Pulmonary emphysema in a nonsmoker with normal alpha-1-antitrypsin. AB - Premature and rapidly progressing emphysema of the lung is unique in the absence of cigarette smoking or an inherited homozygous alpha-1-antitrypsin deficiency. We describe a young man with radiographic evidence of early onset bullous emphysema without the usual risk factors and provide a review of the alternative explanations proposed for this form of lung damage. PMID- 1500833 TI - DaCosta's syndrome: chronic symptomatic hyperventilation. AB - In 1871, DaCosta published his observation of somatic symptoms preceded by significant hyperventilation. More than a century later, the hyperventilation syndrome remains a poorly defined but common clinical condition. Although familiar to most practitioners of medicine when it presents as an acute phenomenon, the diagnosis may go unrecognized in its chronic form. The ability of a chronic hyperventilatory state to mimic a life-threatening cardiopulmonary disease is not always appreciated. PMID- 1500834 TI - Nonsteroidal anti-inflammatory drug induced renal syndromes. AB - Nonsteroidal anti-inflammatory drugs (NSAIDs) may cause acute renal failure from unopposed vasoconstriction or acute interstitial nephritis. NSAID induced hemodynamic renal failure is characterized by sudden oliguria, often with decreased fractional excretion of sodium, occurring in patients with decreased effective circulating fluid volume or preexisting renal disease. Allergic interstitial nephritis from NSAIDs may occur at any time during therapy with the drugs and may present as renal failure with or without the nephrotic syndrome. Although chronic renal failure has been reported, both renal syndromes usually resolve when treatment with the NSAID is discontinued. Renal function should be measured soon after initiation of therapy in patients at risk for the hemodynamic effects of the drugs and periodically thereafter. Patients should be warned about the potential toxicity of the drugs. PMID- 1500835 TI - Health care is too important to be left to the physicians. PMID- 1500836 TI - Elevating maternal insulin-like growth factor-I in mice and rats alters the pattern of fetal growth by removing maternal constraint. AB - Fetal growth is normally constrained by maternal factors. This constraint is demonstrated by the usual inverse linear relationship between litter size and mean fetal weight. Cross-breeding experiments between mice of lines selected for high or low plasma insulin-like growth factor (IGF-I) levels suggested that elevations in maternal IGF-I abolish (P less than 0.01) this constraining effect and reverse the usual positive relationship between fetal and placental size in late gestation. This was confirmed by treating mice and rats throughout pregnancy with IGF-I. In normal mice and in low IGF-I line mice treatment with IGF-I (10 micrograms 8-hourly s.c. from day 1 to 19 of pregnancy) abolished maternal constraint whereas 0.9% (w/v) NaCl treatment did not. In Wistar rats osmotic pumps were implanted to deliver IGF-I (1 microgram/g body weight per day), bovine GH (bGH; 0.6 microgram/g body weight per day) or saline from day 1 to 19 of pregnancy. IGF-I therapy but not bGH or saline abolished (P less than 0.01) maternal constraint and altered (P less than 0.01) the relationship between placental and fetal weight. When high or low IGF-I line mice embroys were transplanted into a normal line of mice, the expected negative relationship (P less than 0.05) between mean fetal weight and litter size was maintained. However, the embryos of the high line were heavier (P less than 0.05) than those from the low line irrespective of fetal number, suggesting a direct role for IGF I in the regulation of fetal growth.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1500837 TI - A comparison of plasma vasopressin and oxytocin concentrations during the oestrous cycle of the ewe. AB - Blood samples were collected twice daily (09.30 and 17.00 h) via indwelling jugular-vein cannulae from five ewes throughout an entire oestrous cycle. Additional frequent samples were taken at 30-min intervals for 8 h on each of days 3 (early luteal phase), 9 (midluteal phase), 12 (late luteal phase) and 0 (day of oestrus). Plasma concentrations of arginine vasopressin and oxytocin were measured in all samples by radioimmunoassay and progesterone was measured in the twice-daily samples only. Both oxytocin and progesterone showed the expected pattern of plasma concentrations, increasing during the early luteal phase, reaching a plateau and declining either preceding (oxytocin) or at (progesterone) luteolysis. Vasopressin concentrations showed a significant dependence on the day of cycle (P less than 0.05, analysis of variance) with concentrations lowest at oestrus and minor peaks on days 4 and 8-9. There was no correlation between the concentrations of vasopressin and progesterone. Vasopressin values were significantly higher in the morning than in the afternoon samples (1.3 cf. 0.9 pmol/l; P less than 0.001). Analysis of the frequent samples showed a significant (P less than 0.001) dependence on the time of day for vasopressin but not oxytocin. Values were high throughout the morning, declined to a trough at 15.00 h and rose again by 17.00 h. We conclude that there is a minor variation in the vasopressin concentration during the oestrous cycle, which is not related to the circulating progesterone concentration but could be regulated by oestradiol. We also provide evidence for a diurnal rhythm in the release of vasopressin into the plasma in the ewe.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1500838 TI - Effect of active immunization of heifers against inhibin on plasma FSH concentrations, ovarian follicular development and ovulation rate. AB - To study the effects of immunoneutralization of endogenous inhibin on gonadotrophin secretion and ovarian function, prepubertal heifers (n = 6) were actively immunized against a synthetic peptide replica of the N-terminal sequence of bovine inhibin alpha subunit (bI alpha(1-29)Tyr30) coupled to ovalbumin. In contrast to ovalbumin-immunized controls (n = 6), bI alpha(1-29)Tyr30-immunized heifers had detectable inhibin antibody titres (% binding to 125I-labelled bovine inhibin at 1:2000 dilution of plasma) of 17 +/- 3% (S.E.M.) at puberty, rising to 31 +/- 5% by the end of the study period 7 months later. Neither age (immunized: 295 +/- 8 days; controls: 300 +/- 5 days) nor body weight (immunized: 254 +/- 13 kg; controls 251 +/- 9 kg) at onset of puberty differed between groups. Although the difference did not reach statistical significance, mean plasma FSH concentrations recorded in inhibin-immunized heifers remained 35-40% higher than in controls throughout the 12-week period leading up to puberty (P = 0.14) and during nine successive oestrous cycles studied after puberty (P = 0.10). Plasma LH concentrations did not differ between groups at any time during the study. Inhibin immunization had no effect on oestrous cycle length (immunized: 19.8 +/- 0.5 days; controls: 19.9 +/- 0.5 days).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1500839 TI - 3 beta-hydroxysteroid dehydrogenase inhibitor reduces ovarian steroid production but increases ovulation rate in the ewe: interactions with gonadotrophins and inhibin. AB - Two experiments were carried out during the breeding season in ewes, first to investigate the effects of oral administration of a 3 beta-hydroxysteroid dehydrogenase (3 beta-HSD) inhibitor (epostane) on the number of corpora lutea, and secondly to investigate the mechanism through which epostane acts. In the first experiment Dorset Horn ewes were treated orally with 25, 50, 100 or 200 mg epostane twice daily between days 10 and 15 of the oestrous cycle. All doses of epostane resulted in an increase in the number of corpora lutea per ewe, although the response was curvilinear, with the 25 mg dose showing the largest response and the 200 mg group the smallest response. Although there was no difference between groups in the number of ewes showing oestrus, the higher doses of epostane had a detrimental effect on fertility. In the second experiment Welsh Mountain ewes were treated twice daily with 25 mg epostane from day 10 of the oestrous cycle and the ovaries were removed for analysis during either the luteal or the follicular phases. Treatment significantly increased the number of follicles greater than 6 mm in diameter, but significantly reduced in-vitro follicular oestradiol and testosterone production. Despite a marked increase in peripheral inhibin concentrations there was no effect on in-vitro inhibin production. Epostane treatment also caused a significant reduction in peripheral FSH concentrations and an increase in mean LH concentration. The latter was due to an increase in LH pulse frequency during the luteal phase and LH pulse amplitude during the follicular phase. These results confirm that treatment of ewes with epostane orally has a significant effect on follicular steroidogenesis and causes a significant increase in the number of corpora lutea per ewe. This effect on ovulation rate is not via an increase in peripheral FSH concentration, but may be caused by a reduction in follicular steroid activity either directly on the ovary or via an alteration in the pattern of LH secretion. PMID- 1500840 TI - Tissue kallikrein is associated with prolactin-secreting cells within human growth hormone-secreting adenomas. AB - Tissue kallikrein is a serine protease which may be involved in the intracellular processing of prolactin in the anterior pituitary gland. The expression of tissue kallikrein, in the rat, is promoted by oestrogen and inhibited by dopamine. Human and rat prolactinomas contain markedly increased amounts of tissue kallikrein; this is comparatively reduced if patients are pretreated with the dopamine agonist, bromocriptine, before surgery. Some GH-secreting adenomas are mixed and also contain prolactin-secreting cells. We therefore investigated 27 GH immunostaining human pituitary adenomas for the presence of immunoreactive tissue kallikrein. Sixteen of the adenomas had positive immunostaining for prolactin; eight of these patients had associated clinical hyperprolactinaemia before the tumour was removed. Tissue kallikrein immunoreactivity was found in ten adenomas, all of which also had prolactin immunopositivity. There was a close relationship between the percentage of cells staining for prolactin and tissue kallikrein but not for GH. A further eight adenomas had patchy positivity, i.e. less than 1% of cells immunostained for tissue kallikrein and six of these also had some prolactin-staining cells. Nine out of eleven purely GH-staining adenomas had no tissue kallikrein immunopositivity, the remaining two showing patchy staining. A review of bromocriptine responsiveness, as assessed by mean GH hormone levels during oral glucose tolerance tests before and after therapy was commenced, indicated that patients with adenomas which stained for prolactin and tissue kallikrein were more likely to respond to bromocriptine than those which failed to do so. PMID- 1500841 TI - The supraoptic nucleus in the pig hypothalamus: postnatal development and the effect of gonadal steroids. AB - Postnatal development of the supraoptic nucleus (SON) in the pig hypothalamus was studied morphometrically. The volume of the SON increased from 6.2 +/- 0.45 (S.E.M.) mm3 at 7 weeks postnatally to 18.5 +/- 1.35 mm3 at 2.5 years of age. A sex difference was found at the development point when the SON volume increased, with earlier SON enlargement in males. This sex difference was 30% at 30 weeks and 50% at 1 year of age. At 2.5 years of age no difference in volume was apparent between the sexes. The number of SON neurones was similar for all age groups concerned (43,500 +/- 1475), except for the 2.5-year-old females where 40% more were found (55,500 +/- 3285). No significant difference was found in neurone number between gonadectomized and sham-operated animals, but the operation caused a 30% reduction in the number of neurones and SON volume. Testosterone supplementation following gonadectomy, during the first 4 weeks postnatally, resulted in sexual dimorphism, the males having more SON neurones than the females. The volume showed only a trend in the same direction. Testosterone supplementation at other ages did not result in any difference when compared with controls. The results of this study show that the postnatal development of the SON of the pig is sexually dimorphic, and that it continues after puberty in females. In contrast to the vasopressin- and oxytocin-containing nucleus, the development of the SON was not influenced by gonadectomy and only slightly by gonadal steroids. PMID- 1500842 TI - Concanavalin-A-bound and -unbound prolactin in normal and hyperprolactinaemic rats. AB - Concanavalin-A (Con-A)-bound and -unbound forms of prolactin were studied in female Wistar-Furth rats, both normal and with hyperprolactinaemia induced by treatment with oestrogen or a prolactinoma graft. In normal rats, Con-A-bound prolactin was the major circulating form (more than 50%) and a minor pituitary component (less than 10%), essentially as 25 kDa prolactin. In oestrogen-treated rats, plasma prolactin levels were 100-fold higher and pituitary weight was fivefold higher than in the controls, but total pituitary prolactin content was unmodified. Under oestrogen, Con-A-bound prolactin represented about one-third of the total hormone levels in the plasma and less than 10% in the pituitary. In the pituitary, bound prolactin was found essentially as 25 kDa and unbound prolactin as 22, 30 and 40-45 kDa. A similar increase in plasma prolactin levels was induced 6 months after the graft of a prolactinoma. Pituitary weights and total pituitary prolactin contents were slightly decreased. Plasma and pituitary Con-A bound prolactin levels were similar to those observed in oestrogen-treated rats. On the other hand, unbound prolactin was only present as a 22 kDa monomer. In the tumour, Con-A-bound prolactin (essentially as 25 kDa prolactin) represented one third of the total hormone level and unbound prolactin was composed of the 22 and 45 kDa forms, this latter form being partially transformed into 22 kDa by heating.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1500843 TI - Antiprogesterone RU486 induces dissociation of LH and FSH secretion in the cyclic rat: effect of anti-inhibin serum. AB - Administration of the antiprogesterone RU486 to 4-day cyclic rats from metoestrus to pro-oestrus increases serum levels of LH while decreasing levels of FSH. If it is assumed that there is only one gonadotrophin-releasing hormone, there is no direct explanation for the decrease in FSH concentrations. The purpose of these experiments was to investigate the effect of RU486 on gonadotrophin secretion in cyclic rats during periods when the secretion of LH and FSH diverges. RU486 blunted the transient increase in FSH concentration on the afternoon of metoestrus and the compensatory ovarian hypertrophy on the next day of oestrus in unilaterally ovariectomized 4-day cyclic rats. In addition, bilateral ovariectomy reversed the effect of RU486 on the basal secretion of FSH. RU486 induced an increase in basal LH concentrations. Since ovarian inhibin decreases the basal release of FSH, and decreases in peripheral inhibin seem to be responsible for the transient rise in FSH during the oestrus cycle, the effect of RU486 on serum levels of LH and FSH during dioestrus in rats injected with a sheep anti-inhibin serum (AIS) were further evaluated. Treatment with AIS increased FSH levels in oil-treated rats without altering the levels of LH. In contrast, the effects of AIS on FSH secretion were blunted in RU486-treated rats. The results suggest that inhibin might be involved in the RU486-induced decrease of FSH secretion in cyclic rats. PMID- 1500844 TI - Antiprogesterone RU486 increases serum immunoreactive inhibin levels and LH:FSH and testosterone:oestradiol ratios in cyclic rats. AB - Since administration of the antiprogesterone RU486 to cyclic rats results in a dissociation of basal LH and FSH secretion we studied its effects on peripheral levels of inhibin, oestradiol and testosterone throughout the oestrous cycle. Cyclic rats were given RU486 (2 mg) twice daily (09.00 and 17.00 h) on metoestrus, dioestrus and pro-oestrus. Oil-treated rats were used as controls. Serum concentrations of immunoreactive inhibin in oil-treated rats increased from metoestrus to pro-oestrus and decreased at oestrus. RU486-treated rats had serum inhibin concentrations significantly increased over oil-treated rats at dioestrus and pro-oestrus, but not at oestrus. At both pro-oestrus and oestrus serum concentrations of LH, testosterone and oestradiol were significantly raised in RU486-treated rats compared with oil-treated controls. In contrast, serum FSH concentrations in RU486-treated rats were decreased on both days. Ovaries from RU486-treated rats showed an increased testosterone content at pro-oestrus, mainly in the interstitial tissue. The results of the present study demonstrate that RU486 has a stimulatory effect on inhibin secretion, and offer an explanation for the decrease in basal serum FSH levels. The low FSH secretion on the morning of oestrus in spite of the low levels of inhibin suggests that progesterone is involved in FSH secretion at this time. PMID- 1500845 TI - Short-term changes in the 3,5,3'-tri-iodothyronine nuclear receptor-binding capacity of porcine skeletal muscle following food intake. AB - The time-course of changes in the nuclear 3,5,3'-tri-iodothyronine (T3) receptor binding capacity (Bmax) of longissimus dorsi muscle has been investigated in cold acclimated young pigs after a single large meal. Measurement of Bmax values 4, 8, 12 and 24 h after feeding indicated a decline in receptor numbers after food intake with the lowest values occurring at 8 h. The receptor numbers then increased significantly, with the values at 12 h being more than 50% higher than those obtained at 8 h. The Bmax values reached their highest level 24 h after feeding. No significant changes in the dissociation constant were observed. Possible reasons for the changes in T3 receptor numbers are discussed and it is suggested that the increase in T3 receptor numbers 12-24 h after feeding may play a role in enhancing the thermogenic capacity of the tissues in response to food. PMID- 1500846 TI - Discordant secretion of relaxin by individual porcine large luteal cells: quantitative analysis by a reverse haemolytic plaque assay. AB - Individual large luteal cells (LLC) derived from pregnant swine differ conspicuously in their ability to secrete the peptide hormone relaxin under basal and stimulated conditions--the phenomenon of functional heterogeneity. The purpose of this study was to quantitate knowledge of this phenomenon through use of a reverse haemolytic plaque assay, a technique that utilizes antibody directed, complement-mediated erythrocyte lysis to detect hormone secretion by single LLCs in culture. Measurement of individual plaque areas (an index of the amount of relaxin secreted) demonstrated an approximate 100-fold range in the amount of relaxin secreted by a single cell under basal conditions. This range was doubled by exposure to the phorbol ester, 4 beta-phorbol 12 beta-myristate 13 alpha-acetate (PMA; 50 nmol/l). Under basal conditions, 50 and 80% of the total amount of relaxin was secreted by approximately 10 and 30% of all LLCs respectively. The size of these fractions was not influenced by the time of incubation (1-8 h), or by the presence of either of two non-specific stimulatory relaxin secretagogues, PMA (50 nmol/l) or arachidonic acid (1 mumol/l). The unimodal frequency distribution of plaque areas (under basal or stimulated conditions) suggests that relaxin-secreting LLCs comprise a discrete functional population of secretory cells, at least under these experimental conditions. We conclude that a remarkably small fraction of LLCs secretes the majority of relaxin, and that the size of this fraction was not influenced by time or secretagogues. PMID- 1500847 TI - The ontogenic and functional relationships between growth hormone- and prolactin releasing cells during the development of the bovine pituitary. AB - The ontogeny of GH- and prolactin-releasing cells in the developing bovine pituitary was evaluated by reverse haemolytic plaque assays which allows for the detection of hormone release from individual pituitary cells in culture. With this approach, we observed that GH-releasing cells ontogenically preceded prolactin-releasing cells. In fact, GH secretors were observed as early as 59 days of gestational age while cells that released prolactin were not identified until 98 days. The amounts of both GH- and prolactin-releasing cells increased with time to reach more than 50% and 20% of all pituitary cells near term (term approximately 280 days) respectively. Interestingly, the first cells shown to release prolactin also released GH (i.e. were mammosomatotropes). This temporal and functional relationship between GH and prolactin secretors provides suggestive evidence that GH-secreting cells act as the progenitor cells for prolactin secretors via a functional intermediate, the mammosomatotrope. PMID- 1500848 TI - Effects of gonadotrophin-releasing hormone, recombinant human activin-A and sex steroid hormones upon the follicle-stimulating isohormones secreted by rat anterior pituitary cells in culture. AB - FSH is produced and secreted from the anterior pituitary gland of rats in multiple molecular forms. At times of high gonadotrophin-releasing hormone (GnRH) and oestrogen output (e.g. the morning of the day of pro-oestrus) the pituitary increases the production of FSH isoforms with isoelectric point (pI) values greater than 5.0, whilst sex steroid deprivation leads to the production of strongly acidic and less in-vitro biologically active FSH molecules. It is not known, however, whether sex steroids modulate the production of specific FSH isoforms by a direct action at the pituitary level or indirectly through altering the rate of synthesis and/or secretion of GnRH. In order to obtain some insight on this issue, we examined the charge heterogeneity of FSH secreted by cultured pituitary cells exposed to different FSH-releasing factors, oestradiol-17 beta and progesterone, alone or in different time-sequenced combinations. Anterior pituitary glands from 21-day-old female rats were enzymatically dispersed into a single cell suspension and cultured for 5 days. During days 1 to 3, cells were incubated in the absence of factors or steroid hormones; on days 3 to 4, cells were incubated in the absence (controls) or presence of either oestradiol-17 beta (3.67 nmol/l) or oestradiol-17 beta plus progesterone (3.67 and 31.8 nmol/l respectively). Finally, during days 4 to 6, GnRH (10 nmol/l) or recombinant human activin-A (2 nmol/l) were added to half of all culture wells. Media from each cell group were concentrated and the several forms of secreted FSH were then separated by polyacrylamide gel isoelectric focusing (pH range 6.5-4.0) and quantitated. All media concentrates contained several forms of immunoactive secreted FSH focusing within a pH range of 6.44-4.23. A large amount (51-76%) of total FSH recovered focused within a pI range of 4.9-4.0 (area 3), whilst 20-43% and 4-8% of the total were identified within pI range of 5.9-5.0 (area 2) and 6.5 6.0 (area 1) respectively.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1500849 TI - Desialylation of lysosomal membrane glycoproteins by Trypanosoma cruzi: a role for the surface neuraminidase in facilitating parasite entry into the host cell cytoplasm. AB - Trypanosoma cruzi enters host cells via formation of an acidic vacuole which is subsequently disrupted, allowing the parasite access to the cytoplasm. We show that in an acid environment, release of the parasite surface neuraminidase is enhanced, and this release is likely mediated by a phosphatidylinositol-specific phospholipase C (PIPLC), since antibodies to a carbohydrate epitope (CRD) revealed in glycosylphosphatidylinositol (GPI)-anchored proteins after PIPLC cleavage remove the great majority of the soluble neuraminidase activity from culture supernatants. The neuraminidase is active at acidic pH, and is capable of desialylating known vacuolar constituents, i.e., lysosomal membrane glycoproteins. Parasite escape into the cytoplasm is significantly facilitated in terminal sialylation-defective mutant Lec 2 cells, and enzymatically desialylated membranes are more susceptible to lysis by a parasite hemolysin previously implicated in vacuole membrane rupture. These findings provide evidence that terminal sialylation on carbohydrate moieties contributes to maintaining lysosomal membrane integrity, and indicate a role for a protozoan-derived neuraminidase in facilitating parasite entry into host cells. These observations raise the possibility that other microbial neuraminidases may serve a similar function in acidic intracellular compartments. PMID- 1500850 TI - Switch recombination breakpoints are strictly correlated with DNA recognition motifs for immunoglobulin S gamma 3 DNA-binding proteins. AB - The deletion looping out model of switch (S) recombination predicts that the intervening DNA between switch regions will be excised as a circle. Circular excision products of immunoglobulin switch recombination have been recently isolated from lipopolysaccharide (LPS)-stimulated spleen cells. The recombination breakpoints in these large circles were found to fall within switch regions. Since switch recombination is clearly focused on switch regions, we hypothesized that some DNA-binding protein factor might be involved in specifically recognizing and facilitating the alignment of switch regions before recombination. Two DNA-binding proteins that specifically interact with two discrete regions of the S gamma 3 tandem repeat have been identified in crude and partially purified nuclear extracts derived from LPS- and dextran sulfate (DxS) activated splenic B cells. The first factor has been found indistinguishable from NF-kappa B by mobility shift assays, methylation interference, competition binding studies, and supershift analysis using an antiserum specific for the p50 component. The second appears to be composed of two closely traveling mobilities that do not separate upon partial purification. This second complex is unique and specific for S gamma 3 by methylation interference assays and competition-binding analysis. The sites at which recombination occurs in the S gamma 3 switch region have been analyzed and found to strictly correlate with the binding sites of the S gamma 3 switch binding proteins. PMID- 1500851 TI - Association of the tyrosine kinase LCK with phospholipase C-gamma 1 after stimulation of the T cell antigen receptor. AB - Stimulation of the T cell antigen receptor (TCR) activates a protein tyrosine kinase and leads to the tyrosine phosphorylation of phosphoinositide-specific phospholipase C-gamma 1 (PLC gamma 1). The molecular interactions involved in this phosphorylation are not known. After stimulation of the TCR on Jurkat T cells, tyrosine-phosphorylated proteins of 36, 38, 58, and 63 kD coprecipitate with PLC gamma 1. An identical pattern of proteins precipitate with TrpE fusion proteins that contain the Src homology (SH) 2 domains of PLC gamma 1, indicating that these regions of PLC gamma 1 are responsible for binding. TCR stimulation leads to an association between the SH2 domains of PLC gamma 1 and a protein tyrosine kinase, which, by peptide mapping, is identical to p56lck. These studies establish that p56lck associates with PLC gamma 1 as a result of TCR stimulation of Jurkat cells, suggesting that p56lck plays a central role in coupling the TCR to the activation of PLC gamma 1. PMID- 1500852 TI - Unexpected effects of the severe combined immunodeficiency mutation on murine lymphomagenesis. AB - Strain C.B17 scid/scid (SCID) mice, which lack functional T and B lymphocytes, show heightened susceptibility to the induction of thymic lymphomas by x irradiation. Susceptibility is highest in thymus-chimeric SCID-BL mice (thymectomized SCID mice bearing a C57BL thymus graft). All SCID-BL lymphomas originate in the cells of the thymic graft (C57BL type) and lack murine leukemia virus expression. Both SCID and SCID-BL lymphomas are phenotypically CD4-8+ and/or CD4+8+, but only the SCID-BL tumors express CD3. Injection of C57BL or BALB/c bone marrow into irradiated SCID-BL mice prevents lymphoma development, but SCID marrow is completely ineffective. The results suggest that the scid condition enhances the activity of a putative lymphomagenic agent induced in the bone marrow by x-irradiation and that C57BL thymic cells are highly sensitive targets. Moreover, the failure of SCID bone marrow to protect against lymphomagenesis vs. the efficacy of marrow from immunocompetent donors points to involvement of T or B lineage cells in this process. PMID- 1500853 TI - Correlation between lymphocyte-induced donor-specific tolerance and donor cell recirculation. AB - Intravenous infusion of mice with major histocompatibility complex (MHC) incompatible lymphocytes can inhibit the response of recipient T cells capable of recognizing the injected cells, and can enhance survival of grafts sharing MHC with the injected cells. However, neither T cell inactivation nor graft survival enhancement is always achieved. This is particularly true for donor cells that are fully allogeneic (as compared to semiallogeneic) to the recipient. We show here that both donor-specific induced response reduction and graft survival enhancement are directly correlated with the ability of the injected lymphoid cells to persist in the recirculating lymphocyte pool of the host. Whether donor cells persist correlates inversely with the level of natural killer cell (NK) activity in the host. Fully allogeneic cells can only persist in hosts with low NK activity and can then induce response reduction. Both persistence and response reduction are abrogated by injection of the host with poly-I:C, a treatment that boosts host NK activity. The same treatment also destroys the ability of semiallogeneic injected cells to persist, to induce response reduction, and to enhance skin graft survival. PMID- 1500854 TI - A major surface protein on group A streptococci is a glyceraldehyde-3-phosphate dehydrogenase with multiple binding activity. AB - The surface of streptococci presents an array of different proteins, each designed to perform a specific function. In an attempt to understand the early events in group A streptococci infection, we have identified and purified a major surface protein from group A type 6 streptococci that has both an enzymatic activity and a binding capacity for a variety of proteins. Mass spectrometric analysis of the purified molecule revealed a monomer of 35.8 kD. Molecular sieve chromatography and sodium dodecyl sulfate (SDS)-gel electrophoresis suggest that the native conformation of the protein is likely to be a tetramer of 156 kD. NH2 terminal amino acid sequence analysis revealed 83% homology in the first 18 residues and about 56% in the first 39 residues with glyceraldehyde-3-phosphate dehydrogenase (GAPDH) of eukaryotic or bacterial origin. This streptococcal surface GAPDH (SDH) exhibits a dose-dependent dehydrogenase activity on glyceraldehyde-3-phosphate in the presence of beta-nicotinamide adenine dinucleotide both in its pure form and on the streptococcal surface. Its sensitivity to trypsin on whole organism and its inability to be removed with 2 M NaCl or 2% SDS support its surface location and tight attachment to the streptococcal cell. Affinity-purified antibodies to SDH detected the presence of this protein on the surface of all M serotypes of group A streptococcal tested. Purified SDH was found to bind to fibronectin, lysozyme, as well as the cytoskeletal proteins myosin and actin. The binding activity to myosin was found to be localized to the globular heavy meromyosin domain. SDH did not bind to streptococcal M protein, tropomyosin, or the coiled-coil domain of myosin. The multiple binding capacity of the SDH in conjunction with its GAPDH activity may play a role in the colonization, internalization, and the subsequent proliferation of group A streptococci. PMID- 1500855 TI - Natural occurrence and origin of somatically mutated memory B cells in mice. AB - While most murine peripheral B cells express germline-encoded antibodies of classes M and D (mu+ delta+ cells), small numbers of memory B cells expressing somatically mutated immunoglobulin G antibodies are generated upon T cell dependent immunization. Analyzing the antibody repertoire of the mu-delta- B cell pool in unimmunized mice, we show that these cells express somatically mutated VH genes and that most of these genes derive from a set of germline VH genes dominantly expressed by mu+delta+ B cells. Thus, class-switched memory B cells are generated in the absence of intentional immunization, presumably in response to environmental antigens. These cells are either recruited from mu+delta+ B cells or selected from newly arising B cells in parallel to the latter, by the same antigens. PMID- 1500856 TI - T cell receptor-mediated recognition of self-ligand induces signaling in immature thymocytes before negative selection. AB - Shaping of the T cell repertoire by selection during intrathymic maturation involves T cell receptor (TCR) recognition of major histocompatibility complex/self-antigen complexes. In this communication, we studied the ability of minor lymphocyte stimulating (Mls) determinants to act as self-tolerogens in the selection of the T cell repertoire. We demonstrate that unprimed T cells from normal as well as TCR transgenic mice form Mls-specific conjugates with antigen presenting cells, and that this TCR-ligand interaction leads to elevation of intercellular Ca2+ ([Ca2+]i). Peripheral T cells from TCR transgenic mice expressing receptors specific for self-Mls antigen show no reactivities to Mlsa. However, a proportion of immature thymocytes from these mice show specific binding and strong [Ca2+]i elevation in response to self-antigen-presenting cells, although these thymocytes do not proliferate. This self-reactivity of thymocytes is inhibited by antibodies specific for TCR, CD4, CD8, class II molecules, lymphocyte function-associated antigen 1, and intercellular adhesion molecule 1. These results demonstrate for the first time that before thymic negative selection, immature T cells can specifically interact with cells bearing self-antigen, and suggest that the resulting TCR-dependent signal transduction events provide a basis for negative selection of self-reactive T cells. PMID- 1500857 TI - Two subsets of epithelial cells in the thymic medulla. AB - Information was sought on the features of epithelial cells in the murine thymic medulla. The expression of major histocompatibility complex (MHC) molecules on medullary epithelium was defined by light microscopy with the aid of bone marrow chimeras and MHC-transgenic mice. A proportion of medullary epithelial cells was found to show conspicuously high expression of conventional MHC (H-2) class I (K, D, L) and class II (I-A, I-E) molecules. These cells express a high density of the Y-Ae epitope, a complex of an E alpha peptide and I-Ab molecules found on typical bone marrow-derived cells. MHC+ medullary epithelial cells show limited expression of I-O molecules, a class of atypical nonpolymorphic MHC-encoded class II molecules present on B cells. Other medullary epithelial cells express a high density of I-O molecules but show little or no expression of typical MHC class I or II molecules. MHC and I-O expression thus appear to subdivide medullary epithelial cells into two phenotypically distinct subsets. This applies in adults. In the embryonic thymus most medullary epithelial cells express both types of molecules. PMID- 1500858 TI - The human immunodeficiency virus gp120 binding site on CD4: delineation by quantitative equilibrium and kinetic binding studies of mutants in conjunction with a high-resolution CD4 atomic structure. AB - The first immunoglobulin V-like domain of CD4 contains the binding site for human immunodeficiency virus gp120. Guided by the atomic structure of a two-domain CD4 fragment, we have examined gp120 interaction with informative CD4 mutants, both by equilibrium and kinetic analysis. The binding site on CD4 appears to be a surface region of about 900 A2 on the C" edge of the domain. It contains an exposed hydrophobic residue, Phe43, on the C" strand and four positively charged residues, Lys29, Lys35, Lys46, and Arg59, on the C, C', C", and D strands, respectively. Replacement of Phe43 with Ala or Ile reduces affinity for gp120 by more than 500-fold; Tyr, Trp, and Leu substitutions have smaller effects. The four positively charged side chains each make significant contributions (7-50 fold). This CD4 site may dock into a conserved hydrophobic pocket bordered by several negatively charged residues in gp120. Class II major histocompatibility complex binding includes the same region on CD4; this overlap needs to be considered in the design of inhibitors of the CD4-gp120 interaction. PMID- 1500859 TI - Characterization of the interleukin 2 receptors (IL-2R) expressed on human natural killer cells activated in vivo by IL-2: association of the p64 IL-2R gamma chain with the IL-2R beta chain in functional intermediate-affinity IL-2R. AB - Interleukin 2 (IL-2) receptors expressed on the surface of activated T cells and natural killer (NK) cells exhibit a variety of affinity states depending on their subunit composition. Low-affinity binding is associated with a 55-kDa alpha chain, intermediate-affinity binding with a 70-75-kD beta chain, and high affinity binding with a bimolecular complex of the alpha and beta subunits. In a previous study of the IL-2 receptors expressed on NK cells obtained from cancer patients after in vivo IL-2 therapy, we documented a discrepancy between the level of beta chain and the level of intermediate-affinity IL-2 binding sites expressed on the cell surface. Based on this result, we postulated that formation of intermediate-affinity receptor sites required a component in addition to the beta chain, and that this component was present at limiting levels in the patient NK cells. In the present study we have examined the structure of the intermediate affinity receptor complex using monoclonal antibodies that recognize the beta chain, but that do not interfere with its ability to bind IL-2. Evidence is presented establishing the physical association of a novel protein of 64 kD with the beta chain in intermediate-affinity IL-2 binding sites. This molecule, termed IL-2R gamma chain, coprecipitated with beta chains prepared from cells that had been incubated with IL-2, but was undetectable in immunoprecipitates prepared in the absence of IL-2. Examination of gamma chain expression in post-IL-2 therapy NK cells, where only low levels of intermediate-affinity IL-2 binding were detectable, revealed that the gamma chain was associated with, on average, only 10-12% of the beta chains expressed on such cells. This contrasted with approximately equal levels of beta and gamma chain expression on YT cells, a cell line that has both high levels of cell surface beta chain expression and high levels of IL-2 binding. Thus, the ratio of gamma chain to beta chain present in the immunoprecipitates roughly correlated with the proportion of beta chain involved in intermediate-affinity receptor sites. This result suggests that the 64-kD gamma chain is the component responsible for regulating the affinity of IL 2 association with the beta subunit. By further defining the structural components necessary for IL-2 receptor formation, these studies provide additional insight into mechanisms whereby lymphocytes might regulate their responsiveness to IL-2. PMID- 1500860 TI - Systemic lupus erythematosus patients with central nervous system involvement show autoantibodies to a 50-kD neuronal membrane protein. AB - An antibody was detected in the sera from patients with systemic lupus erythematosus (SLE) and central nervous system (CNS) involvement that reacted with a 50-kD antigen in the plasma membrane of brain synaptic terminals. The 50 kD antigen was solubilized with Triton X-100 from preparations enriched with synaptic plasma membranes, and was partially purified by molecular sieve filtration column chromatography. The sera of 19 of 20 CNS-SLE patients showed strong to moderate immunoreactivity with the 50-kD protein in Western blots. Immunoreactivity with the 50-kD protein was also detected in the cerebrospinal fluid of CNS-SLE patients. Control sera from healthy individuals did not react with the 50-kD protein. Low to background reactivity was detected in 35% of a group of SLE patients without CNS manifestations, and in 3% of patients displaying other connective tissue diseases. A total of 100 individuals were tested in this study. Purified autoantibodies to the 50-kD protein from CNS-SLE patients were used for immunofluorescent labeling of neuroblastoma cells. The immunofluorescent staining revealed a distinct macular distribution pattern on the surface of the cell membrane. Taken together, the data suggest that the 50-kD protein may be an important target for autoantibodies, preponderantly found in CNS-SLE patients, and that the antigen may play a role in the pathogenesis of some neurological manifestations in SLE. PMID- 1500861 TI - Memory T cells are anergic to the superantigen staphylococcal enterotoxin B. AB - We have used staphylococcal enterotoxin B (SEB) to study the role of naive and memory T cells in the induction of peripheral tolerance. After administration of SEB to mice, the numbers of naive and memory T cells increase, as does the proportion of memory T cells, which are unresponsive to further stimulation with SEB in vitro. In addition, memory T cells generated in response to conventional antigen, which proliferate and provide help to B cells in the presence of the conventional antigen, fail to respond to superantigen. Hence, memory T cells, in general, are anergized by SEB. These results suggest that SEB-induced activation and anergy reflect the combined responses of naive and memory T cells. The differential activation vs. anergy of naive and memory T cells by superantigen may be related to cytokine production and may play an important role in the etiology of autoimmune diseases or immunodeficiency diseases such as acquired immune deficiency syndrome. PMID- 1500862 TI - Growth of epithelial cells in the thymic medulla is under the control of mature T cells. AB - Epithelial cells in the thymic medulla are conspicuous in normal adult mice, but sparse in the early fetal thymus and the thymus of adult T cell-deficient SCID mice. To examine whether growth of medullary epithelial cells (MEC) depends upon local contact with mature T cells, we used the finding that the SCID thymus is unusually permeable to mature T cells entering from the bloodstream. When SCID mice received multiple injections of mature lymph node T cells from birth, the thymus accumulated large numbers of mature TCR+ T cells of resting phenotype, but contained virtually no immature (CD4+8+) cells. The injected T cells localized in the medullary region of the thymus and led to marked regeneration of MEC. These and other data suggest that the growth of MEC is under the control of mature T cells. Placing MEC under T cell control might be a device for regulating the size and integrity of the medulla, especially during the phase of rapid thymic growth. Maintaining the cellular components of the medulla in proper balance could be critical for ensuring efficient self tolerance induction. PMID- 1500863 TI - Inhibition of tumor growth in vivo with a soluble CD44-immunoglobulin fusion protein. AB - CD44H is the principal cell surface receptor for hyaluronate, which is a major glycosaminoglycan of the extracellular matrix. Expression of CD44H is enhanced in a variety of malignant tumors and correlates with tumor aggressiveness, supporting the notion that interaction between CD44H and hyaluronate may play an important role in tumor growth and dissemination. In this report we show that in vivo tumor formation by human lymphoma Namalwa cells, stably transfected with CD44H, can be suppressed by a soluble human CD44H-immunoglobulin fusion protein. Disruption of the interaction between CD44H and its physiologic ligands may provide a novel strategy for controlling tumor growth in vivo. PMID- 1500864 TI - Evaluation of the functional equivalence of major histocompatibility complex class II A and E complexes. AB - Most mice display two conventional major histocompatibility complex class II isotypes, A and E. Several A+E- strains have been observed, but never any that are A-E+. Because of this and because of hints from several lines of functional analysis, it has been proposed that the two isotypes might not operate equivalently. This proposition has not been directly testable until now because of the lack of an E-only strain. We report the production of such mice, exploiting previously created class II-transgenic and class II-"knock-out" lines. A+E-, A-E-, and A-E+ littermates have been compared by a number of parameters. We find that E and A molecules are, for the most part, functionally equivalent. However, subtle differences are seen in their ability to engage CD4 molecules on immature thymocytes, and in the profile of receptors on T cells selected into the periphery. PMID- 1500865 TI - Biological movements look uniform: evidence of motor-perceptual interactions. AB - Six experiments demonstrate a visual dynamic illusion. Previous work has shown that in 2-dimensional (2D) drawing movements, tangential velocity and radius of curvature covary in a constrained manner. The velocity of point stimuli is perceived as uniform if and only if this biological constraint is satisfied. The illusion is conspicuous: The variations of velocity in the stimuli exceed 200%. Yet movements are perceived as uniform. Conversely, 2D stimuli moving at constant velocity are perceived as strongly nonuniform. The illusion is robust: Exposure to true constant velocity fails to suppress it. Results cannot be explained entirely by the kinetic depth effect. The illusion is evidence of a coupling between motor and perceptual processes: Even in the absence of any intention to perform a movement, certain properties of the motor system implicitly influence perceptual interpretation of the visual stimulus. PMID- 1500866 TI - The role of balance dynamics in the active perception of orientation. AB - The Stoffregen and Riccio (1988) hypothesis that perceived orientation is determined primarily by balance dynamics was tested. Perception of orientation was evaluated in the context of a task that required Ss to control the roll orientation of a device in which they were seated. The device's direction of balance was manipulated across trials and thus was independent of gravity. Eighteen Ss participated in the investigation. After each trial, Ss estimated their mean tilt with respect to upright. Correlations of perceived tilt with tilt from balance were consistently higher than the correlations with gravity tilt. The dominance of balance over gravity depended on the magnitude of tilt from balance. PMID- 1500867 TI - Symmetry breaking dynamics of human multilimb coordination. AB - The dynamics of pattern formation and change are studied in a complex multicomponent system, specifically the arms and legs of human Ss. Among the novel features observed are differential stability of coordinative modes produced by limbs moving in the same versus different directions (Experiment 1); transitions between coordinative modes preceded by a slow drift in relative phase (Experiments 1 and 2); bifurcations or phase transitions from 1 four-limb pattern to another (Experiment 2); and spontaneous emergence of non-1:1-frequency- and phase-locked patterns, in addition to periods of relative coordination (Experiment 3). All observed relative phasing patterns and their dynamics (stability, loss of stability, intermittency) are shown to arise from the same underlying nonlinear dynamical structure, an important feature of which is broken symmetry. PMID- 1500868 TI - Influence of animation on dynamical judgments. AB - The motions of objects in the environment reflect underlying dynamical constraints and regularities. The conditions under which people are sensitive to natural dynamics are considered. In particular, the article considers what determines whether observers can distinguish canonical and anomalous dynamics when viewing ongoing events. The extent to which such perceptual appreciations are integrated with and influence common-sense reasoning about mechanical events is examined. It is concluded that animation evokes accurate dynamical intuitions when there is only 1 dimension of information that is of dynamical relevance. This advantage is lost when the observed motion reflects higher dimension dynamics or when the kinematic information is removed or degraded. PMID- 1500869 TI - Changing affordances in stair climbing: the perception of maximum climbability in young and older adults. AB - This experiment extended Warren's leg-length model by investigating the relevance of leg strength and joint flexibility on perceptual judgments of climbability. From a set of 8 stairs (riser heights: 38-91 cm), 24 older and 24 young adults were asked to identify the highest stair they could climb without using their hands or knees. Ss then attempted to climb the selected stair. Tall and short young observers perceived similar action boundaries despite leg-length differences. Tall and short older adults had divergent action boundaries when a single-scale leg-length model was applied. A regression model that used flexibility and leg-strength measurements provided a better fit of the older adult data, indicating that models applying functional (kinematic and kinetic) criteria might be useful in describing lawful relationships between organisms and the environment. PMID- 1500870 TI - Nonvisual judgment of the crossability of path gaps. AB - The ability of persons to locomote without vision with the aid of a hand-held probe was investigated in 4 experiments focusing on the negotiation of gaps in a pathway. In Experiment 1, Ss of extreme heights judged under sighted and blindfolded conditions whether gaps of different sizes could be crossed by walking. Crossability boundaries were lower for shorter Ss, but the height effect disappeared under normalization by leg length. Experiments 2-4 altered mechanical aspects of the probe (length and mass distribution) in the nonvisual case. Ss' performance was still reliable in each experiment, and their performances were constrained by parameters of the gap and of their action systems. Probe variables, however, had surprisingly little influence on the judgments of crossability. Results were discussed in terms of potential roles for information in different perceptual modalities. PMID- 1500871 TI - Role of the inertia tensor in perceiving object orientation by dynamic touch. AB - Ss wielded an occluded L-shaped rod and attempted to perceive the direction in which the rod was pointing with respect to the hand. The pattern of the rod's different resistances to rotation in different directions, quantified by the inertia tensor, changes systematically with the rod's orientation. Perception of orientation by wielding is possible if the tissue deformation consequences of the rod's inertia tensor are detectable. It was shown that perceived orientation was a linear function of actual orientation for both free and restricted wielding and for rods of different-size branches. The eigenvectors of the inertia tensor were implicated as the basis for this haptic perceptual capability. Results were discussed in reference to information-perception specificity and its implications for effortful or dynamic touch. PMID- 1500872 TI - The role of spectral and dynamic cues in imagery for musical timbre. AB - The musical quality of timbre is based on both spectral and dynamic acoustic cues. Four 2-part experiments examined whether these properties are represented in the mental image of a musical timbre. Experiment 1 established that imagery occurs for timbre variations within a single musical instrument, using plucked and bowed tones from a cello. Experiments 2 and 3 used synthetic stimuli that varied in either spectral or dynamic properties only, to investigate imagery with strict acoustic control over the stimuli. Experiment 4 explored whether the dimension of loudness is stored in an auditory image. Spectral properties appear to play a much larger role than dynamic properties in imagery for musical timbre. PMID- 1500873 TI - Perceptual interactions between musical pitch and timbre. AB - These experiments examined perceptual interactions between musical pitch and timbre. Experiment 1, through the use of the Garner classification tasks, found that pitch and timbre of isolated tones interact. Classification times showed interference from uncorrelated variation in the irrelevant attribute and facilitation from correlated variation; the effects were symmetrical. Experiments 2 and 3 examined how musical pitch and timbre function in longer sequences. In recognition memory tasks, a target tone always appeared in a fixed position in the sequences, and listeners were instructed to attend to either its pitch or its timbre. For successive tones, no interactions between timbre and pitch were found. That is, changing the pitches of context tones did not affect timbre recognition, and vice versa. The tendency to perceive pitch in relation to other context pitches was strong and unaffected by whether timbre was constant or varying. In contrast, the relative perception of timbre was weak and was found only when pitch was constant. These results suggest that timbre is perceived more in absolute than in relative terms. Perceptual implications for creating patterns in music with timbre variations are discussed. PMID- 1500874 TI - Musical duplex perception: perception of figurally good chords with subliminal distinguishing tones. AB - In a variant of duplex perception with speech, phoneme perception is maintained when distinguishing components are presented below intensities required for separate detection, forming the basis for the claim that a phonetic module takes precedence over nonspeech processing. This finding is replicated with music chords (C major and minor) created by mixing a piano fifth with a sinusoidal distinguishing tone (E or E flat). Individual threshold intensities for detecting E or E flat in the context of the fixed piano tones are established. Chord discrimination thresholds defined by distinguishing tone intensity were determined. Experiment 2 verified masked detection thresholds and subliminal chord identification for experienced musicians. Accurate chord perception was maintained at distinguishing tone intensities nearly 20 dB below the threshold for separate detection. Speech and music findings are argued to demonstrate general perceptual principles. PMID- 1500875 TI - The sum of the parts does not equal the whole: evidence from bihemispheric processing. AB - The 5 experiments in this article examine whether bihemispheric processing can be predicted from the processing observed when information is directed initially to just 1 hemisphere. Ss decided if laterally presented words rhymed with a previously presented central target. Trials varied in the degree to which the information displayed was redundant. On some trials, the same word appeared twice; in others, different words appeared, but they both led to the same decision; and finally, on some trials, different words appeared, each of which also led to a different decision. The patterns found for unilateral and bilateral trials were distinct. Furthermore, the pattern observed on bilateral trials could not be predicted from that found on unilateral trials, suggesting that interhemispheric interaction cannot be surmised from observing a hemisphere processing information in relative isolation. PMID- 1500876 TI - Global shape cannot be attended without object identification. AB - Whether the global shape of objects can be processed without accessing semantic or identity information was tested. Ss judged which of 2 fragmented forms had the same global shape as a reference stimulus. Matching stimuli could be physically identical, semantically related, or unrelated. The reference stimulus and nonmatching (distractor) form could be semantically related or unrelated. Similarity effects in the related condition were unconfounded with matches nameable and nonnameable forms. For nameable forms, related matching forms facilitated performance; a related distractor disrupted performance. Semantic interference was eliminated when nameable distractors were replaced with nonnameable partners; semantic similarity effects on matching were eliminated with a nonnameable reference stimulus and with inverted targets and distractors. Access to information concerning global shape does not normally occur without object identification. PMID- 1500877 TI - Reference frame and effects of orientation on finding the tops of rotated objects. AB - Effects of stimulus orientation across trial blocks and the spatial reference frame were investigated with a task in which Ss, with their head upright or tilted, judged a dot to be near the top or the bottom of rotated line drawings of objects. Objects used in this task were also named. Response times from the first block of trials increased linearly for objects rotated from 0 degrees to 120 degrees from the upright. Across blocks, orientation effects diminished for naming but remained the same for top-bottom discriminations. Practice with top bottom discriminations diminished orientation effects when the same objects were subsequently named. The spatial reference frame for top-bottom discriminations was midway between retinal and environmental coordinates. Specifying the location of object features is of greater importance for top-bottom discriminations than for naming and underlies orientation effects in these tasks. PMID- 1500878 TI - Selective attention and visual search: revision of an allocation model and application to age differences. AB - The present experiments examined a revised version of the Eriksen and Yeh model of attentional allocation during visual search. The results confirmed the assumption of the model that performance represents a weighted combination of focused- and distributed-attention trials, although Ss relied on focused attention more than was predicted. Consistent with the model, predictions on the basis of the assumption of a terminating search fit the data better than predictions on the basis of an exhaustive search. The effects of varying cue validity favored an interpretation of focused attention in terms of a processing gradient rather than a zoom lens. Although the allocation of attention across trials was similar for young and older adults, there was an age-related increase in the time required to allocate attention within individual trials. PMID- 1500879 TI - Splitting focal attention. AB - The study was based on the inverse relationship between the effect of attention on reaction time (RT) and the size of the area over which focal attention is allocated. Independent occurrence of this in 2 locations in the opposite hemifields would be evidence of attention splitting. In Experiment 1, in which the 2 locations were denoted by empty boxes, there was an inverse relationship between size of the stimulated box and RT. Experiment 2 replicated the finding with different stimulation conditions. In Experiment 3, no relationship was found between RT and length of a cuing line. In Experiment 4, in which attention was manipulated by central cues, there was an effect of box size on valid and neutral trials but not invalid trials. Observers could split focal attention and manipulate simultaneously 2 independent attentional foci on objects located in the opposite hemifields. PMID- 1500880 TI - Temporary suppression of visual processing in an RSVP task: an attentional blink? . AB - Through rapid serial visual presentation (RSVP), we asked Ss to identify a partially specified letter (target) and then to detect the presence or absence of a fully specified letter (probe). Whereas targets are accurately identified, probes are poorly detected when they are presented during a 270-ms interval beginning 180 ms after the target. Probes presented immediately after the target or later in the RSVP stream are accurately detected. This temporary reduction in probe detection was not found in conditions in which a brief blank interval followed the target or Ss were not required to identify the target. The data suggest that the presentation of stimuli after the target but before target identification processes are complete produces interference at a letter recognition stage. This interference may cause the temporary suppression of visual attention mechanisms observed in the present study. PMID- 1500881 TI - Response time distributions and the Stroop Task: a test of the Cohen, Dunbar, and McClelland (1990) model. AB - Cohen, Dunbar, and McClelland's (1990) model was tested for Strooplike interference tasks by studying the shape of the distribution of response latencies produced by Ss and by the model. The model correctly anticipates changes in mean response latency (M(RT)) across congruent and incongruent conditions. It does not, however, correctly anticipate changes in the shape of the distributions, even though changes in the shape of the distributions underlie the changes in M(RT). Thus the model predicts M(RT) successfully but for the wrong reason. It is concluded that the model is not an adequate account of Ss' performance in the Stroop task. PMID- 1500882 TI - Mechanisms of ion and acid-base regulation at the gills of freshwater fish. AB - This review examines the branchial mechanisms utilized by freshwater fish to regulate internal acid-base status and presents a model to explain the underlying basis of the compensatory processes. Rainbow trout, Oncorhynchus mykiss, and brown bullhead, Ictalurus nebulosus, were examined under a variety of experimental treatments which induced respiratory and metabolic acid-base disturbances. Acid-base regulation was achieved by appropriate adjustments of Na+ and Cl- net fluxes across the gills which, in turn, were accomplished by variable contributions of three different branchial mechanisms: 1) differential changes in Na+ and Cl- diffusive effluxes, 2) changes in internal substrate (H+, HCO3-) availability, and 3) morphological adjustments to the gill epithelium. Differential diffusive efflux of Na+ over Cl- was involved only during periods of metabolic alkalosis. The importance of internal substrate availability was demonstrated using a two-substrate model. According to the model, ionic flux rates (J(in)Cl-, J(in)Na+) are determined not only by the concentration of the external ion (Na+, Cl-) but also by the concentration of the internal counterion (H+, HCO3-). This system provides for an "automatic negative feedback" to aid in the compensation of metabolic acid-base disturbances. Morphological alteration of the gill epithelia and the associated regulation of chloride cell (CC) fractional area is an essential third mechanism which is especially important during respiratory acid-base disturbances. Specifically, fish vary the availability of the CC associated Cl-/HCO3- exchange mechanism by physical covering/uncovering of CCs by adjacent pavement cells. PMID- 1500883 TI - Intracellular pH regulation and metabolic interactions in hepatic tissues. AB - Intracellular pH (pHi) regulation in the vertebrate liver relies heavily on ionic transport mechanisms. Liver, in common with many tissues, has plasma membrane Na(+)-H+ and Cl(-)-HCO3- electroneutral exchangers which work in opposition to tightly control pHi. Mammalian livers also possess electrogenic Na(+)-HCO3- exchangers, capable of base uptake, which, when coupled to pHi-mediated changes in membrane potential, probably confer an additional measure of pHi control, compared to fish livers, where the transporter appears to be functionally absent. It is suggested that this may be a fundamental difference between aquatic and aerial breathing. pHi regulation has barely been examined in invertebrate hepatic tissues, but already some interesting differences are apparent. Notably, an electrogenic 2Na(+)-1H+ acid-extrusion system is present in apical membranes of crustacean hepatopancreas. Despite these ionic control systems, complex acid-base disturbances (e.g., "metabolic" acidosis) have been known for some time to influence hepatic metabolism in vertebrates, but few studies have carefully examined the independent effects of the acid-base variables involved. Thus mechanistic explanations for the effects of acid-base disturbances are scarce. Ureogenesis in mammals has been well studied, and several pH-related mechanisms are evident. In contrast, the pH-insensitivity of ureogenesis in fish liver may represent a second difference between aquatic and terrestrial species. In summary, by virtue of its metabolic diversity, liver represents a potentially important organ in acid-base balance, and an interesting study tissue for interrelationships between metabolism and acid-base balance. PMID- 1500884 TI - Cytoskeletal sheets appear as universal components of mammalian eggs. AB - The eggs of two mammalian species have been shown to contain novel cytoskeletal elements, referred to as cytoskeletal sheets, which undergo stage-specific changes in spatial organization at three key developmental transitions, fertilization, compaction, and blastocyst formation. If cytoskeletal sheets have an integral role in these developmental transitions, the sheets should be present in the eggs of other mammals as well. We examined the eggs of four additional species to determine if sheets were present. Our results indicate that sheets were present and they can be categorized into two classes based on their surface appearance. Cytoskeletal sheets in eggs of hamsters and rats have a smooth surface appearance, while eggs from humans, cows, pigs, and mice have a fibrous surface appearance. In addition, we observed that species-specific variations exist in the width of the sheets and in the density of the sheets (i.e., number per micron 2) in the eggs. These species-specific variations may relate to the role of the sheets during early development. PMID- 1500885 TI - Xenopus laevis sperm proteins, previously identified as surface proteins with egg coat binding capability, are indeed histone H4, histone H3, and sperm specific protein SP2. AB - Recently, four Xenopus sperm proteins thought to be involved in binding to the egg envelope were identified (Lindsay and Hedrick, J. Exp. Zool., 245:286-293, '88). We have studied the three more abundant ones of apparent molecular weight of 14, 19, and 25 kd in SDS-PAGE. We have shown that these proteins are indeed nuclear basic proteins: the 14 kd is the histone H4, the 19 kd is the histone H3, and the 25 kd is the sperm-specific protein SP2. PMID- 1500887 TI - Discussion of "Alleged brain damage, diminished capacity, mens rea, and misuse of medical concepts". PMID- 1500886 TI - Immunocytochemical analysis of the association of bovine oviduct-specific glycoproteins with early embryos. AB - The bovine oviductal epithelium synthesizes and secretes a class of oviduct specific glycoproteins that is present in the luminal fluid when fertilization and early embryonic development occur. The objective of this study was to determine if these characterized glycoproteins become associated with oviductal embryos. Ovarian ova and oviductal embryos were recovered from super-ovulated cows at 72 h after onset of estrus. Eggs were fixed in 3% paraformaldehyde-1% glutaraldehyde and subsequently embedded in Lowicryl K4M. Sections (1 micron) were processed for peroxidase-antiperoxidase immunocytochemistry. Immunolabeling was not detected in any region of ovarian ova. Oviductal embryos, regardless of cleavage stage, exhibited immunoperoxidase staining localized within their zona pellucidae. Sections (100 nm) obtained from a 4- and an 8-cell embryo were also subjected to colloidal gold immunoelectron microscopy to determine conclusively the subcellular distribution of the oviduct-specific glycoproteins. Gold particles were distributed uniformly throughout the width of the zona pellucida. Also, immunoreactivity was observed associated with flocculent material in the perivitelline space and with the vitelline membrane. These results indicate that the bovine oviduct-specific secretory glycoproteins become associated with oviductal embryos. This association may be biologically important to the developing embryo. PMID- 1500888 TI - Reporting of highly individual genetic typing results: a practical approach. AB - This paper considers the interpretation of serological typing data as a problem in forensic science, as opposed to a problem in population genetics or statistics. Controversies arising in this area are partly due to an overly narrow perspective that ignores basic forensic science principles. After an initial discussion of the special problem that deoxyribonucleic acid (DNA) blood typing poses to forensic science, the three difficulties common to all the proposed interpretive methods are discussed. These are: predicting genotype incidence from allele frequencies, predicting frequencies for the joint occurrence of genotypes in a number of different genetic marker systems, and determining the appropriate population to use to measure the frequencies. The inability to test assumptions that are inherent in our routine methods is noted. This is a procedural weakness that unnecessarily limits the admissibility of DNA typing evidence in court. A practical solution to this problem is offered that begins with minimal assumptions. Initially a statement is made based on (1) how many reference samples the laboratory has typed and (2) how many of these samples show genotypes corresponding to the case samples. The second stage of the presentation begins with a statement that additional assumptions are necessary to fully interpret the evidence and that although these assumptions are scientifically very reasonable, they cannot be absolutely proven. The presentation can then proceed, if desired, to consideration of the specific assumptions and frequency estimates of any of the methods that have been proposed to date. To follow this approach population data must be kept in a form that allows the simple first-stage statement to be made. This means that each individual's record would include typing results in each genetic marker system. Although this method of data storage differs from that used in most forensic science laboratories, it is exceptionally versatile, and allows great flexibility in data analysis. PMID- 1500889 TI - Isolation of deoxyribonucleic acid (DNA) from saliva and forensic science samples containing saliva. AB - Saliva and saliva-stained materials were examined as potential sources of deoxyribonucleic acid (DNA) for DNA analysis and identity testing. In this paper, the authors demonstrate that DNA was isolated and DNA banding patterns suitable for DNA typing were obtained from fresh saliva and various saliva-stained materials, such as envelopes, buccal swabs, gags, and cigarettes. Furthermore, DNA and DNA banding patterns were obtained from actual forensic evidentiary samples containing mixed saliva/semen stains. The DNA banding patterns obtained from saliva or saliva-stained material were indistinguishable from the patterns obtained from blood or hair from the same individual. Intact DNA was readily isolated and DNA banding patterns were obtained from saliva stored at -20 degrees C and dried saliva stains stored under varying conditions. We conclude that saliva and saliva-stained material can be good sources of DNA for analysis and for DNA typing in certain forensic settings. PMID- 1500890 TI - Ribosomal ribonucleic acid (rRNA) gene typing for species identification. AB - Deoxyribonucleic acid (DNA) typing of ribosomal ribonucleic acid (rRNA) genes was performed with a polymerase chain reaction (PCR) assay for species identification. A variable region of the 28S ribosomal RNA gene was amplified with primers complementary to flanking sequences phylogenetically well conserved. The products of twelve animal DNAs (human, Japanese monkey, dog, cattle, pig, cat, rabbit, mouse, rat, chicken, frog, and fish) were separated by polyacrylamide gel electrophoresis, each revealing a few bands ranging from 150 to 100 base pairs. The band patterns obtained from each DNA sample differed in number and size, which indicates the applicability of the method to species identification. Samples containing either as little as 1 pg of DNA or degraded DNA of 0.2 to 0.5 kb in length were able to give detectable bands. Postmortem human tissue DNAs were tested as an example. They showed a pattern identical to the human control one, which was distinct from those of the other animals examined. PMID- 1500891 TI - The effect of ibuprofen on ethanol concentration and elimination rate. AB - Pursuant to a recent driving under the influence (DUI) case, a medical study of six subjects was cited reporting that ibuprofen causes a decrease in the maximum rate of elimination of ethanol. Such a drug interaction is of significant forensic science interest and warrants further examination. This study investigates the effect of ibuprofen on ethanol elimination rate and ethanol concentration in nineteen volunteers. Volunteer subjects were randomly assigned to two groups administered either a placebo followed by ethanol or ibuprofen followed by ethanol. Subjects served as their own control. Blood ethanol concentrations were monitored every 30 to 60 min for up to 4 h with Intoximeter 3000 instruments. A blood sample was drawn at the final Intoximeter test and analyzed for ethanol and ibuprofen by gas chromatography and mass spectrometry, respectively. The mean elimination rate (+/- SD) as calculated using Widmark's elimination factor was 0.018 +/- 0.006 g/dL for ethanol and 0.017 +/- 0.007 g/dL/h for ethanol with ibuprofen. Mean ethanol concentrations (g/dL +/- SD) were: 0.095 +/- 0.026 (ethanol) and 0.095 +/- 0.033 (ethanol and ibuprofen) at 30 min; 0.077 +/- 0.026 (ethanol) and 0.075 +/- 0.031 (ethanol and ibuprofen) at 150 min; and 0.089 +/- 0.025 (ethanol) and 0.087 +/- 0.030 (ethanol and ibuprofen) overall. There was no statistically significant affect of ibuprofen on either the peak blood ethanol concentration or the ethanol elimination rate (p less than or equal to 0.001). These results reveal no evidence of a significant ethanol ibuprofen interaction. PMID- 1500892 TI - Comparison analysis of illicit cocaine samples. AB - A rapid method for comparison analysis of illicit cocaine samples has been developed. The raw data are obtained by capillary gas chromatography using a nitrogen-phosphorus detector. The area ratios of four alkaloids (tropacocaine, norcocaine, cis-cinnamoylcocaine, and trans-cinnamoylcocaine) to cocaine are calculated for each sample. These ratios are compiled in a computer database which allows easy comparison of samples and makes possible reliable conclusions regarding their commonality of origin. PMID- 1500893 TI - A rapid gas chromatographic method for the fingerprinting of illicit cocaine samples. AB - A gas chromatographic (GC) fingerprint method, based on the presence or absence of six congeners, was developed for illicit cocaine samples. The fingerprint utilizes the relative abundances of these congeners towards each other, disregarding cocaine as the main constituent, and can be expressed numerically or graphically in the form of pictograms for rapid visual comparison. The method can be applied directly to a solution of the sample in chloroform, without previous workup procedures. More than 70 unrelated samples were analyzed and a great variation was observed in the parameter composition. On the other hand, a remarkable similarity could be seen between related samples. The GC fingerprint method may be considered an important contribution for sample comparison, as is exemplified by a subdivision of the analyzed samples in different categories, based on the number and types of congeners found. PMID- 1500894 TI - The analysis and identification of steroids. AB - In October 1987, anabolic steroids were controlled under Schedule IV of Florida State Statute 893. This study was designed to establish a method of analysis and identification of evidentiary cases. Spot tests, Fourier transform infrared spectroscopy (FT-IR), gas chromatography/mass spectroscopy (GC/MS), Fourier transform nuclear magnetic resonance (FT-NMR), thin-layer chromatography (TLC), and extractions were performed on standard and pharmaceutical steroids. Mandelin's accompanied by the sulfuric acid test was found to provide the best indication of a steroid among the following four spot tests performed: sulfuric acid, napthol-sulfuric acid, Liebermann's, and Mandelin's. TLC was successfully performed on the steroid samples using two different eluent systems: TP and TQ. GC/MS was a very useful method of analysis applicable to most steroids, with only a few exceptions. FT-IR spectra were found to match the spectra from the literature for all the standards tested. The combination of the above techniques was used successfully to identify all the standards tested. PMID- 1500895 TI - Fourier transform infrared/Raman differentiation and characterization of cis- and trans-2,5-dimethoxy-4,beta-dimethyl-beta-nitrostyrenes: precursors to the street drug STP. AB - Fourier transform Raman and infrared spectra of pure cis(Z)- and trans(E)-2,5 dimethoxy-4,beta-dimethyl-beta-nitrostyrene (precursors of the psychotomimetic street drug STP or DOM) were recorded in the solid state. The spectra show characteristic features of the ethylene moiety and of the aryl and nitro substituents which permit ready differentiation and identification of these isomers. A very strong Raman line at 1670 cm-1 from the cis isomer for the C=C stretching mode, in comparison with a strong Raman line at 1641 cm-1 for the trans isomer, affords primary differentiation of these substances. A second characteristic, of both the Raman and infrared (IR) spectra, is that the frequency of the strong symmetric nitro (NO2) stretching band is about 40 cm-1 higher in the cis (1346 cm-1) than the trans isomer (1301 cm-1). All major IR and Raman bands are reported and given vibrational assignments. PMID- 1500896 TI - Differentiation of side chain isomers of ring-substituted amphetamines using gas chromatography/infrared/mass spectrometry (GC/IR/MS). AB - Common analytical methods used for identifying samples obtained from clandestine laboratories were evaluated for their ability to differentiate between possible amphetamine isomers and homologs. A series of ring-substituted (4-methyl, 4 methoxy, and 3,4-methylenedioxy) amphetamine and N-methylphenethylamine isomers was analyzed using color tests, thin-layer chromatography, gas chromatography/mass spectrometry (GC/MS) and GC/infrared (GC/IR). The N-acetyl derivatives of the isomers were analyzed using GC/IR/MS. GC/IR/MS readily differentiated the 4-methylphenylalkylamine isomers. MS and IR spectra were also obtained for each pair of the 4-methoxyphenylalkylamine isomers and the 3,4 methylenedioxyphenylalkylamine isomers, but differentiation via GC/IR/MS was difficult. The N-acetyl derivatives of each pair of isomers could be readily differentiated using GC/IR/MS. Good library researchable spectra for N acetylamphetamine could be obtained for IR identification with 10 ng (on-column) and MS identification with 2 ng. The spectrometrically independent IR and MS data obtained for the N-acetyl derivatives indicated that the combination of GC/IR/MS can add a significant level of confidence in the analysis of ring-substituted arylalkylamines. PMID- 1500897 TI - Neck injuries: I. Occipitoatlantal dislocation--a pathologic study of twelve traffic fatalities. AB - Twelve of 155 persons killed in traffic crashes had occipitoatlantal dislocations. Nine were vehicular occupants, 2 were cyclists, and one was a pedestrian. The dislocations involved various combinations of lacerations of the alar ligaments, the occipitoatlantal joint capsules, the dura mater, the tectorial membrane, the rectus capitis muscles, and the suboccipital muscles. In 2 instances, an occipital condyle failed instead of the corresponding alar ligament, producing condyle fractures. Atlas ring fractures occurred in 3 instances. Axial and subaxial cervical trauma were uncommon. Facial or mandibular fractures occurred in a majority of cases, vault skull fractures were uncommon, and basilar fractures were absent. Pontomedullary brainstem lacerations occurred in 9 of the 12, and 4 had midbrain lacerations. The majority of the victims succumbed to acute neurogenic shock as the sole or the major mechanism of death. The biomechanical basis for occipitoatlantal dislocation is discussed, and the author suggests that distraction, in concert with variable combinations of extension, rotation, and posterior translation is responsible for occipitoatlantal dislocations. PMID- 1500898 TI - Neck injuries: II. Atlantoaxial dislocation--a pathologic study of 14 traffic fatalities. AB - C1-C2 vertebral dislocations have not been commonly recognized at autopsy. Among 66 subjects with neck injuries, drawn from a series of 155 traffic fatalities, were 14 with injuries at the level of the atlantoaxial motion segment, ranging in age from 8 months to 93 years. Thirteen had sprains or lacerations of the atlantoaxial facet joints, and one had a healed C1 fracture. Six of the 14 had odontoid fractures. None had transverse ligament lacerations. Injuries of the alar ligaments and the tectorial membrane were frequent. Only 3 subjects had subaxial cervical injury. All 14 had evidence of impact to the head or neck. Four had fractures of the mandible or facial bones, and 5 had skull fractures. Subdural and subarachnoid hemorrhages were found in 7 and 6, respectively. Brainstem lacerations were not uncommon, but only one had a pontomedullary laceration. Spinomedullary cord injuries occurred in 5. Acute neurogenic shock was the major mechanism of death in 9 of the 14, including 5 with major cardiovascular lacerations. Delayed effects of craniocerebral trauma accounted for the majority of the remainder. The biomechanical mechanisms are discussed. PMID- 1500899 TI - Religion, political leadership, charisma, and mental illness: the strange story of Louis Riel. PMID- 1500900 TI - Correlation of trauma and cause of death to accident reconstruction: a case of a flight accident report. AB - This paper reports on the disaster that occurred after a flight was hijacked at Baiyuen International Airport in Guangzhou, China, on Tuesday, 2 Oct. 1990. The authors show the results of analyses for the causes of death and trauma and compare the disaster with several previous flight accidents that have occurred in China. The authors show, with the analysis on this accident, the possibility and reliability of reconstructing a disaster by medicolegal investigation. PMID- 1500902 TI - Comparison of Abbott fluorescence polarization immunoassay (FPIA) and Roche radioimmunoassay for the analyses of cannabinoids in urine specimens. AB - Abbott fluorescence polarization immunoassay (FPIA) and Roche Abuscreen radioimmunoassay (RIA) were compared qualitatively with 142 urine specimens containing 11-nor-delta-9-tetrahydrocannabinol-9-carboxylic acid. Similar qualitative results were obtained in 132 specimens. When discrepent results were observed, all negative results were within 20% of the 100 ng/mL cut-off. We concluded that FPIA and RIA give comparable results to each other. PMID- 1500901 TI - Big game species identification by deoxyribonucleic acid (DNA) probes. AB - Species identification is important in many big game forensic science cases but cannot always be accomplished because of the lack of adequate techniques. The authors have developed deoxyribonucleic acid (DNA) probes for elk, deer, and antelope by isolating highly repeated satellite sequences. These DNA probes distinguish among deer, elk, and antelope, although not between different species of deer. Because of the high number of sequence copies per genome, these probes are extremely sensitive, requiring less than 10 ng of total genomic DNA. The developmental protocol for these probes is relatively simple and is applicable to many other species. PMID- 1500903 TI - Direct analysis for cocaine in urine by high-performance liquid chromatography (HPLC) using a column-switching technique. AB - The analysis of urine for the presence of drugs generally requires that the drug be first extracted from relatively large concentrations of endogenous compounds. By replacing the injection loop with a loop incorporating a cyano precolumn, urine can be injected directly onto the high-performance liquid chromatograph. Interfering compounds are washed off of the precolumn, with the valve in the load position. When the valve is then switched to inject, the mobile phase elutes the cocaine from the precolumn onto the analytical column. A preliminary identification of cocaine and benzoylecgonine can be made using this technique, which requires 100 microL of sample and has a detection limit of 10 ng/mL. PMID- 1500904 TI - Elevator surfing: a deadly new form of joyriding. AB - A new form of joyride, on top of an elevator as it moves up and down the elevator shaft, has surfaced on college campuses and in housing and apartment complexes with elevators. This practice is called "elevator surfing," and an illustrative case is presented, which is believed to be the first such report in the medical literature. PMID- 1500905 TI - Fatal dissecting aneurysm of the internal carotid artery with delayed symptoms following facial impact. AB - A fatal dissecting aneurysm of the internal carotid artery occurred in a 16-year old male following facial impact in an automobile accident. The patient showed no neurologic deficit until two days after the automobile accident, when he suddenly started having seizures and developed right-sided hemiparesis. There was no evidence of direct trauma to the neck externally or internally. The only injuries observed in the head and face were two skin lacerations in the chin area. His condition rapidly deteriorated, and he expired on the fourth hospital day. The gross and microscopic findings for the internal carotid artery are presented. The possible mechanisms for the vascular lesion and a review of the literature are discussed. PMID- 1500907 TI - Our roots. Do they really have value? PMID- 1500906 TI - Bullet identification: a case of a fatal hunting accident resolved by comparison of lead shot using instrumental neutron activation analysis. AB - Bullet identification by chemical analysis often provides a powerful clue in forensic science. A case is reported in which a hunting accident was resolved by using instrumental neutron activation analysis (INAA) for direct comparison of the trace element content in lead shot. Different preparation batches of lead shot appear to have a high within-group composition homogeneity, and good differentiation is achieved between different batches. Determination of the nickel and antimony content on a bush branch demonstrated that the branch had been perforated by one of the shot pellets, and this helped the detectives in reconstruction of the crime scene. PMID- 1500909 TI - The breath of death. PMID- 1500908 TI - Cost shifting. The root of all evil. PMID- 1500910 TI - Contributions of the American Civil War to medicine. PMID- 1500911 TI - Military medicine comes of age. The First World War. PMID- 1500912 TI - The military and Florida's first State Health Officer. PMID- 1500913 TI - To live or to die. Causes of mortality among POWs in South Vietnam. AB - I have attempted to evaluate some of the varied reasons for the mortality among a small group of POWs interred in one camp in Quang-Nam, South Vietnam. There were many factors affecting survival: physical, psychological, social, cultural, racial, and, of course, the whim of fortune. The ancient message seems to be, however, that man is an adaptive animal; he learns from his own experiences as well as the experiences of others. Though he is a product of his environment and may be subjugated and destroyed by a strange one, he constantly attempts to work within it, to mold it, and to rise above it. It is the key to survival. PMID- 1500914 TI - Medical mobilization of Florida's special forces. PMID- 1500915 TI - Desert, dirt and duration. The Persian Gulf war experience. PMID- 1500916 TI - How the AMA represents you. PMID- 1500917 TI - APLU. PMID- 1500918 TI - Educate, inform and empower the public. PMID- 1500919 TI - Sylvester Comprehensive Cancer Center. A celebration of hope. PMID- 1500920 TI - Deep pockets. PMID- 1500921 TI - Letter from the masked man. PMID- 1500922 TI - Positron emission tomography in clinical practice. AB - Positron emission tomography (PET) has been considered a research tool; however, advances in hardware and software, along with availability of small medical cyclotrons, make clinical metabolic imaging feasible. There is accumulating data, especially in the areas of neurology and cardiology, to support its use in the appropriate clinical setting and patient population. PMID- 1500923 TI - Limited incision cholecystectomy. AB - Eighty-one consecutive cholecystectomies were retrospectively reviewed; five were dropped because of incomplete data. The remaining 76 were divided into group A, patients who underwent a limited incision cholecystectomy (LIC) defined as less than 10 centimeters, and group B, those who underwent a standard subcostal incision (STD). An STD was used for 18 patients in 1984 and an LIC for subsequent patients unless anatomy dictated extension of the incision for safe surgical exposure. The groups were evaluated for possible benefits and disadvantages of the LIC approach. Multivariate analysis was done to contrast the approaches regarding operative time, operative and postoperative complications, postoperative pain, and hospital stay. The operative time was comparable between the two groups. The LIC approach was superior with less postoperative pain and shorter hospital stay. There were no intraoperative complications or mortality in either group. The postoperative complications were also comparable. No differences were noted in body size, weight, sex, or whether the patient was suffering from acute or chronic disease. The limited incision cholecystectomy can be utilized in the majority of patients with cholecystitis without added operative time or complications when compared to the traditional approach. The benefits of less postoperative pain, shorter hospital stay and better cosmetic results afford a higher degree of patient acceptance. This procedure should be considered when open cholecystectomy is required. PMID- 1500925 TI - Angel flight. An undiscovered resource. PMID- 1500924 TI - University neonatal centers and level II centers compatibility. Jacksonville experience. AB - Reported are 10 years experience in the development of a Citywide Neonatal Program in the Jacksonville area, which could be helpful as a model for establishing relationships between academic centers and outside Level II nurseries. The four phases of development are documented. An analysis of the financial impact to the academic program is presented and also an outline of the gain realized by the Department of Pediatrics, University of Florida Health Science Center. The positive results in amalgamation of the neonatal services in Jacksonville have far outweighed any potential harmful effects from competition between an academic center and other private nurseries in the city. PMID- 1500926 TI - Hospital risk-management conflicts. PMID- 1500927 TI - R & R fatigue. PMID- 1500928 TI - Parental perceptions and psychopathology. AB - Various theories of personality and psychopathology hypothesize that there should be a relationship between parental perceptions and level of psychopathology. However, there has been relatively little research investigating the parental perceptions-psychopathology relationship, and much of the research in this area has been methodologically flawed. The present study tested four hypotheses regarding the parental perceptions-psychopathology relationship, using a parental representations measure that circumvents many of the problems that have characterized previous research on this topic. Results indicated that psychiatric patients (N = 66): a) viewed both parents more negatively than did members of a matched sample of 66 normal subjects; b) expressed significantly greater ambivalence regarding both parents than did normal subjects; and c) described both parents at a more primitive conceptual level than did normal subjects. As predicted, there was a parallel relationship between perceptions of the parents and overall level of psychopathology within the inpatient sample. The findings are discussed in the context of traditional trait-oriented personality theories as well as more recent social learning theories of personality. PMID- 1500929 TI - Fear of abandonment and binge eating. A subliminal psychodynamic activation investigation. AB - Dependency and fear of abandonment by significant others have been theoretically linked to eating disorders, particularly bulimia. This research investigates the hypothesis that unconscious fear of abandonment is one variable underlying binge eating episodes in bulimia. An analogue population of 40 "high eating disorder" undergraduate women and 40 undergraduate women with normal eating patterns viewed either an abandonment or a control stimulus presented at either subliminal (4 msec) or supraliminal (200 msec) exposure durations. Following exposure to an abandonment stimulus, the high eating disorder group ate significantly more crackers in a bogus cracker rating task (p less than .001) than did subjects in any other condition. Contrary to predictions, a subliminal stimulus did not lead to a significant change in self-reported mood. Results provide preliminary support for the psychoanalytic hypothesis that binge eating is a defense against unconscious fear of abandonment. PMID- 1500930 TI - The relationship of life adversity, social support, and coping to hospitalization with major depression. AB - We evaluated the relationship between life events, social support, coping, and depression in 27 male inpatients meeting the requirements for Research Diagnostic Criteria major depressive disorder and in 35 age- and sex-matched nonpatients. Overall, the hospitalized depressed patients reported significantly more events and difficulties than did the controls, but this difference in statistical significance disappeared after excluding from analysis "non-independent" happenings which could have been brought on by depression. More hospitalized depressed patients (23 of 27, or 85%) than controls (8 of 35, or 22.9%) experienced markedly threatening events and difficulties ("marked adversities") in the 6 months before their interview. The depressed group also reported having significantly fewer social supports, being less satisfied with the emotional component of this support, and using more emotion-focused coping than the controls. A discriminant analysis predicted depressive status from a combination of marked adversities, reduced number of social supports, and greater use of emotion-focused coping. The results indicate that the relationship of life events to depression is complex. The excess number of events might be partly a product of dysfunctional behavior that "produces" depression-related events which might, in turn, exacerbate depression; simultaneously, patients are more likely to experience highly adverse events which might precipitate the depression in the first place. Reduced social supports and the use of emotion-focused coping appear to also be associated with hospitalization for major depression. PMID- 1500931 TI - Multiple diagnoses in posttraumatic stress disorder in the victims of a natural disaster. AB - A population of the fire fighters who had been exposed to a natural disaster were screened using the General Health Questionnaire 4, 11, and 29 months after a natural disaster. On the basis of these data, a high-risk group of subjects who had scored as cases and probable cases and a symptom-free comparison group were interviewed using the Diagnostic Interview Schedule 42 months after the disaster. The prevalence of posttraumatic stress disorder (PTSD), affective disorders, and anxiety disorders was examined. Only 23% of the 70 subjects who had developed a PTSD did not attract a further diagnosis, with major depression being the most common concurrent disorder. Comorbidity appeared to be an important predictor of chronic PTSD, especially with panic disorder and phobic disorders. The subjects who had only a PTSD appeared to have had the highest exposure to the disaster. Adversity experienced both before and after the disaster influenced the onset of both anxiety and affective disorders. PMID- 1500932 TI - Posttraumatic stress disorder among injured survivors of a terrorist attack. Predictive value of early intrusion and avoidance symptoms. AB - Fifteen injured survivors of a terrorist attack on a civilian bus were followed during their admission, and 12 of the 14 living survivors were examined 10 months later. A substantial amount of distress was found, in the entire group, across the study. Four patients (33%) suffered from diagnosable PTSD on follow-up. Symptoms of intrusion and denial, recorded during admission, failed to predict PTSD, and were not significantly correlated with psychiatric symptoms on follow up. This paper discusses the finding of low predictive validity of early PTSD symptoms, and suggests that measures of arousal should be added to those of cognitive symptoms in future prospective studies of traumatic stress. PMID- 1500933 TI - Negative symptomatology in schizophrenic outpatients. AB - This study examines the prevalence of negative symptoms, and assesses the convergence of negative and depressive symptoms in 60 chronically ill schizophrenic outpatients. Negative symptoms were assessed with the Scale for the Assessment of Negative Symptoms and the negative symptom cluster of the Brief Psychiatric Rating Scale (BPRS). Depressive symptoms were assessed with the depression subscale of the Brief Symptom Inventory and the depressive symptom cluster of the BPRS. A majority of patients in this group of relatively stable, schizophrenic outpatients demonstrated mild to moderate degrees of both negative and depressive symptoms. Correlations were not significant between negative symptom and depressive symptom measures, which suggests that the symptom constructs are relatively independent. Comparisons between a subgroup with prominent negative symptoms (N = 18) and a subgroup with minimal negative symptoms (N = 32) also revealed no significant group differences in variables that characterize clinical course (i.e., age of onset and frequency and duration of hospitalization) or in the severity of depressive symptoms. This lack of any significant differences on the clinical course variables may be partially explained by the heterogeneity of negative symptoms. The constellation of negative symptoms may differ not only in etiology but also in their temporal relationships to other aspects of the patient's clinical course. Longitudinal studies will be needed to track the long-term outcome of negative and depressive symptoms. PMID- 1500934 TI - Dream structure in Parkinson's patients. AB - Dream reports of patients with Parkinson's disease (PD) were analyzed to ascertain whether cognitive deficits associated with this nonfocal brain pathology influence dream structure or dream recall. Fifteen outpatients with idiopathic PD were sampled (diagnosed from 1 to 10 years and currently in stage II or III of Hoehn and Yarh's scale); all were without psychiatric symptoms or major medical illnesses and were currently being treated with L-dopa. After an adaptation night in the sleep laboratory, each patient spent a night in which he/she was awakened at least twice in rapid eye movement sleep and asked to report dream experience. Thirteen patients were able to report at least one dream. Overall frequency of dream recall (71.4%) was fully compatible with normative data for the elderly. Multiple regression analyses showed that both the length of the dream report as story and the organization of contents into coherent episodes (analyzed using Mandler and Johnson's story grammar) varied significantly in relation to level of cognitive functioning and, in part, of language comprehension, but not in relation to age, illness duration, and dose of L-dopa. PMID- 1500935 TI - The use of electroconvulsive therapy in patients with dissociative disorders. AB - The psychiatric literature generally discourages the use of electroconvulsive therapy (ECT) to treat depression in dissociative disorder patients, but contains little data on outcome. This prospective study of ECT in three dissociative disorder patients demonstrates that ECT is indicated for severe treatment resistant depression in such patients. Their Hamilton Depression Scale scores fell by 50%, they were remarkably clinically improved, and they maintained their gains for at least 4 months. The ECT proved helpful when depression was felt by most of the active alters rather than just by one depressed personality. Mini Mental State Examination scores and clinical observation revealed no unusual confusion or side effects from ECT. These patients' dissociated condition was not altered by ECT, which indicates that ECT neither treats nor impairs treatment of dissociation. Electroconvulsive therapy can be helpful in the overall treatment of dissociative disorders by alleviating severe depressions which block utilization of psychotherapy. PMID- 1500936 TI - The Separation-Individuation Inventory. Association with borderline phenomena. AB - The Separation Individuation Inventory (SII; Christenson and Wilson, J. Nerv. Ment. Dis., 173:561-565, 1985) was designed to assess adult psychopathology construed in terms of the concepts of separation and individuation (Mahler, Pine, and Bergman, The Psychological Birth of the Human Infant: Symbiosis and Individuation, 1975). Its reported use is confined to the original authors' paper, which compared scores of 20 subjects with borderline personality disorder with the scores of staff control subjects. We report the association of the SII with two self-report measures of borderline personality diagnosis and phenomenology. Our British samples, from the staff and residents in a therapeutic community for severely personality-disordered clients, thus complement the original American work. The SII was found to have good internal consistency, respectable screening parameters, and high correlations with indications of trait psychopathology. We suggest a slight modification to the scoring of the inventory and two main areas for additional research. PMID- 1500937 TI - Comparability of telephone and face to face diagnostic interview schedules. PMID- 1500938 TI - Obsessive-compulsive disorder onset after removal of a brain tumor. PMID- 1500939 TI - An untoward side effect of clozapine. PMID- 1500940 TI - Effect of external urinary collection system on colonization and urinary tract infections with Pseudomonas and Klebsiella in men with spinal cord injury. AB - Urinary tract infection of men with spinal cord injuries has been associated with a high incidence of colonization of the patients with gram-negative bacilli. We have examined the factors influencing colonization of 119 patients with Pseudomonas and Klebsiella and studied methods of reducing this colonization. The urethra, perineum, rectum, and drainage bag of all patients were cultured on selective media at two week intervals until discharge. The use of the external urinary collection system (EUCS) was discontinued in a group of patients at night, in an attempt to reduce colonization. Pseudomonas and Klebsiella were isolated from one or more body sites in 65 percent and 69 percent of total culture days. The urethra, perineum, rectum, and drainage bags were reservoirs of Pseudomonas and Klebsiella in men with spinal cord injuries, even in the absence of urinary tract infections. The EUCS proved to be an important factor influencing colonization. Pseudomonas and Klebsiella colonization was higher in patients using the EUCS. Removal of the EUCS at night reduced urethral colonization with Pseudomonas, but did not significantly reduce urethral colonization with Klebsiella. The prevalence of bacteriuria with Pseudomonas and Klebsiella was not significantly influenced by the use of the EUCS. PMID- 1500941 TI - The serum lipoprotein profile in veterans with paraplegia: the relationship to nutritional factors and body mass index. AB - Individuals with spinal cord injury have a shortened life expectancy, with coronary heart disease as a leading cause of death. Identifying potentially reversible risk factors would be expected to be of value in the long-term care of the person with a spinal cord injury. We addressed the relationships among diet, body mass index, and serum lipid levels in 28 veterans with paraplegia compared to 52 age-matched ambulatory veteran controls. There are no significant differences in body mass index or in total caloric, saturated fat, or cholesterol intake between those with paraplegia and the control group. The serum HDL cholesterol level is significantly lower in those with paraplegia compared to the control group (35 +/- 2 vs 49 +/- 2 mg/dL). There are no significant differences noted in serum total cholesterol, LDL cholesterol, or triglycerides between the groups. Total caloric intake decreases significantly with age in the control subjects but not in the subjects with paraplegia. Inverse correlations are found between serum HDL cholesterol and serum triglycerides levels both in those with paraplegia (r = -0.54, p less than 0.005) and in the controls (r = -0.42, p less than 0.001). In our group of subjects with paraplegia, serum lipid levels appear to be independent of dietary intake and body weight. PMID- 1500942 TI - Immobilization osteoporosis in paraplegia. AB - The pathophysiology of osteoporosis as it relates to immobilization or disuse osteoporosis in paraplegics is briefly reviewed. The physiology of bone formation and resorption is discussed, and the influence of piezoelectric forces on bone integrity and the consequences of the loss of this effect in paraplegics is addressed. When bone is stressed, negative charges accumulate on the side from which the stress is applied and positive charges accumulate on the opposite side. Presumably the collagenous component of bone plays the major role in the generation of electrical potentials. Another mechanism important in the generation of electrical potentials is created by liquid planes streaming past solid planes. Diminished forces acting on bone, as in paraplegia, are translated into changes in the activity of bone remodeling units which can be assessed by histomorphic and histoenzymatic techniques. Other biochemical and endocrine consequences of immobilization involve increased serum calcium, decreased serum parathyroid hormone (PTH), and decreased dihydroxy-vitamin D synthesis. Urinary hydroxyproline and calcium excretion are increased, as is stool calcium. The bone loss that follows immobilization may produce an increased susceptibility to fractures involving long bones more than the spinal column, and is due more to decreased bone formation than to accelerated bone resorption. The treatment of immobilization osteoporosis primarily involves early remobilization, but other treatments, including the use of electrical fields and the administration of bisphosphonates, calcitonin, and a growth hormone are being actively investigated. PMID- 1500943 TI - Autonomic hyperreflexia with spinal cord injury. AB - Autonomic hyperreflexia occurs in up to 85 percent of individuals with spinal cord injuries above the major splanchnic sympathetic outflow. In such cases, paroxysmal reflex sympathetic activity develops in response to noxious stimuli below the level of the neurologic lesion. The clinical features of autonomic hyperreflexia are due largely to reflex sympathetic adrenergic and cholinergic discharges with dysfunctional supraspinal regulatory control. Cephalgia, diaphoresis, flushing, tachycardia or bradycardia, and paroxysmal hypertension are most commonly observed. Although a variety of stimuli can provoke autonomic responses of variable magnitudes, bladder and bowel distention continue to account for most episodes. Removal of the offending stimulus is important to restoring the autonomic nervous system to its baseline activity. Current understanding of the pathophysiology, clinical features, and medical management of this fascinating but potentially serious complication of spinal cord injury are reviewed. PMID- 1500944 TI - Applying functional analysis to psychological rehabilitation following spinal cord injury. AB - There have been numerous attempts to categorize the responses of individuals to spinal trauma on the basis of generalized stage theories of grief reaction, and personality theory. A number of these studies are critically appraised and a behavioral model, based on functional analysis, is proposed as a more constructive framework for future research. Such an approach is applied clinically to the activities and development of the Clinical Psychology Service provided to the Mersey Regional Spinal Injuries Centre in Southport, England. A number of examples of clinical and research practice are included, highlighting the applicability of functional analysis to individual and systems level investigations. PMID- 1500945 TI - The prevention and management of urinary tract infections among people with spinal cord injuries. National Institute on Disability and Rehabilitation Research Consensus Statement. January 27-29, 1992. AB - The Urinary Tract Infection Consensus Conference brought together researchers, clinicians, and consumers to arrive at consensus on the best practices for preventing and treating urinary tract infections in people with spinal cord injuries; the risk factors and diagnostic studies that should be done; indications for antibiotic use; appropriate follow-up management; and needed future research. Urinary tract infection (UTI) was defined as bacteriuria (102 bacteria/ml of urine) with tissue invasion and resultant tissue response with signs and/or symptoms. Asymptomatic bacteriuria represents colonization of the urinary tract without symptoms or signs. Risk factors include: over-distention of bladder, vesicoureteral reflux, high pressure voiding, large post-void residuals, presence of stones in urinary tract, and outlet obstruction. Possible physiologic/structural, behavioral, and demographic risk factors were identified also. Indwelling catheterization, including suprapubic, and urinary diversion are the drainage methods most likely to lead to persistent bacteriuria. Infection risk is reduced with intermittent catheterization, but more severely disabled people who require catheterization by others are at greater risk for UTIs. Clean self-intermittent catheterization does not pose a greater risk of infection than sterile self-intermittent catheterization and is much more economic. However, care must be given to proper cleansing of reusable catheters. Quantitative urine culture criteria for the diagnosis of bacteriuria include: catheter specimens from individuals on intermittent catheterization greater than or equal to 10(2) cfu/ml; clean-void specimens from catheter-free males using condom collection devices greater than or equal to 10(4) cfu/ml; and specimens from indwelling catheters of any detectable concentration. Dip stick screening tests may offer promise as an early warning system of UTI since they can be self-administered. Symptomatic UTI should be treated with antibiotics for 7 to 14 days. Longer courses have not been beneficial. In patients with symptomatic UTIs, it is not necessary to wait for the results of cultures before starting treatment. Asymptomatic bacteriuria need not be treated with antibiotics. There is little evidence presently to support the use of antibiotics to prevent infections. Following a recent episode of febrile UTI, possible contributing prior events should be reviewed. The upper tracts should be evaluated (imaging studies) to identify possible abnormalities. A common concern among people with spinal cord injuries is that physicians will alter bladder management programs without regard to lifestyle needs. Social/vocational flexibility may be more important to them than a state-of-the-art bladder management program. Future research should focus on obtaining more representative samples and investigate psycho-social-vocational implications as well as additional clinical-medical factors. PMID- 1500947 TI - Immunocytochemical mapping of noradrenergic projections to the rat spinal cord with an antiserum against noradrenaline. AB - The mapping of noradrenergic innervation was performed in transverse and longitudinal sections of the adult rat spinal cord using noradrenaline immunocytochemistry. Noradrenergic fibres and terminals were distributed in the dorsal horn (mainly in the superficial part), in the vicinity of the different groups of motoneurons, and concentrated in the intermediolateral cell column and around the central canal. The ultrastructural study showed principally axodendritic synapses in the ventral horn and in the intermediolateral cell column. Fewer axosomatic synapses were detected. In the dorsal horn, noradrenaline-innervation was predominantly non-synaptic. It is hypothesized that the noradrenergic modulation of nociception is not mediated through classical synapses. The concept of 'volume transmission' can explain such an influence. Conversely, noradrenaline may be involved in the control of locomotion and automatic functions through conventional synapses. PMID- 1500946 TI - Growth of tumour cell lines in polymer capsules: ultrastructure of encapsulated PC12 cells. AB - Recent studies indicate that polymer-encapsulated PC12 cells release sufficient amounts of dopamine to significantly alter behavioural paradigms in animals with unilateral lesions of dopaminergic midbrain neurons. Because cell fine structure provides a useful measure for assessment of storage function, exocytosis, metabolism, cell activity and cell viability, we examined the ultrastructure of PC12 cells grown in semi-permeable polymer capsules maintained in vitro or implanted into the forebrain of rats or guinea pigs. Encapsulated PC12 cells remained viable and continued to divide for the entire evaluation period of six months. Overall morphologies of encapsulated PC12 cells were similar in both environments and they resembled PC12 cells grown in monolayer cultures. In short term cultures, encapsulated PC12 cells typically contained abundant quantities of chromaffin cell-like granules. The encapsulated cells had initially abundant microvilli on their surfaces which decline in frequency over time. After long term enclosure for ten weeks or more, fewer secretory granules were detected in the cytoplasm of cells in capsules cultured in vitro and in brain-implanted capsules. Some cells in implanted capsules had long slender filipodia that were not present on PC12 cells in cultured capsules. The morphological changes of PC12 cells may correlate with altered growth conditions such as serum and oxygen concentrations, the presence or absence of growth factors in different environments, and with changes of cell interactions related to cell densities and build up of debris within the capsules over time. Since dopaminergic PC12 pheochromocytoma cells remain viable in semi-permeable polymer capsules for at least six months, such 'cell-capsules' could provide an alternative to dopamine secreting embryonic neural grafts in dopamine replacement therapies. PMID- 1500948 TI - Early development of the Lurcher cerebellum: Purkinje cell alterations and impairment of synaptogenesis. AB - The postnatal development of the heterozygous Lurcher (Lc/+) mouse cerebellum is characterized by Purkinje cell death with a concomitant reduction in granule cell number. In order to evaluate possible relationships between these two events, this study investigates early morphological abnormalities of the Purkinje cells and possible defects in the formation of their synaptic investment. Cerebella of Lurcher and control age-matched (from P8 to P16) mice were analysed by calbindin immunostaining, silver impregnation and quantitative electron microscopy. Direct signs of Purkinje cell anomaly are obvious from P8, four days before the onset of the necrotic process. These signs include the presence of axonal swellings and perinuclear clumps of chromatin, and a general delayed process of maturation, evidenced in cell bodies (incomplete development of the basal polysomal mass) and in dendritic trees (hyperspinous dendrites, delayed formation of proximal and distal compartments). Also from P8, the external granular layer is reduced in thickness. Despite these abnormalities, the onset of the synaptogenesis between Purkinje cells and their specific inputs (parallel fibres, climbing fibres and basket cell axons) takes place on schedule and, at P8, no defect has been noticed. On and after P10, the rate of parallel fibre synaptogenesis is decreased. Very few climbing fibres translocate from their perisomatic to their peridendritic locations, and basket cell axons fail to develop 'pinceau' formations. All these results suggest that before the death of the Purkinje cell by P12, there is an impaired maturation of these neurons provoked by the Lurcher gene action. The hypoplasia of the external granular layer and the altered synaptic investment of the Purkinje cell after P10 are considered to be consequences of the early Purkinje cell defect. PMID- 1500949 TI - The origin and development of retinal astrocytes in the mouse. AB - Astrocytes, a class of glia which appear in the mammalian retina late in development, have been postulated either to originate in situ from Muller cells or extra-retinally from the optic stalk epithelium, only subsequently invading the eye. The site of origin and the developmental characteristics of retinal astrocytes were examined in the mouse, a species not previously studied for this purpose. Sections of normal eyes and stalks at different ages were examined. Cells positive for glial fibrillary acidic protein (GFAP) were first observed at post-conceptional day 17 at the optic disc end of the stalk. From this site, the GFAP-positive cells migrated into and across the retina at a rate of approximately 290 microns per day, reaching its edge by post-conceptional day 28. While migrating across the retina, the astrocytes progressively increased in size and morphological complexity, observations confirmed by measurement of their fractal dimension. Over the same period, a wave of differentiation swept along the stalk in the cranial direction. Further evidence that retinal astrocytes are born outside the retina emerged when foetal hemiretinae with or without optic stalks were explanted to the chorioallantoic membrane of the chick. When examined one to twelve days later, no explant cultured without the optic stalk contained GFAP-positive astrocytes, while explants with the stalk left attached contained relatively normal numbers of astrocytes. We observed, using fluorescence confocal microscopy, that retinal astrocytes in the mouse as in the rat, associate predominantly with blood vessels, not axonal bundles. It was of interest to determine whether this class of glia is essential to the normal cytoarchitectural development of the neural retina. Morphological analysis of the explants revealed no observable differences in cytoarchitecture or in the timing of developmental events between retinae maturing with or without astrocytes. It was therefore concluded that astrocytes may not be essential to the normal structural development of the murine retina. PMID- 1500950 TI - Sensitometric comparison of direct- and indirect-exposure films used in intraoral radiography. AB - In Japan, some dentists use indirect-exposure (screen) films for intraoral radiography, without the use of intensifying screens. The purpose of the present investigation was to determine whether film speed, inherent contrast, and latitude of Japanese indirect-exposure films used without intensifying screens were comparable to those of direct-exposure (non-screen) films used for intraoral radiography. The characteristic curves of Kodak Ektaspeed ("E" speed) and Ultra speed ("D" speed) films were used as standards for comparison. Indirect-exposure films without intensifying screens were extremely slow compared with direct exposure "E" and "D" speed films. Therefore, they should not be used for intraoral radiography because they needlessly expose the patient to excessive X ray radiation. The direct-exposure films Hanshin Hi-Fi and Hanshin New Silver were equivalent in speed, higher in contrast, and narrower in latitude than Kodak Ektaspeed film. In general, the indirect-exposure films had lower speed, lower contrast and wider latitude than the direct-exposure films. Their speed and contrast would have been increased if intensifying screens had been used. Therefore, indirect-exposure films without intensifying screens should not be used for intraoral radiography. PMID- 1500951 TI - Finite element model of facial soft tissue. Deformation following surgical correction. AB - The finite element method is used to predict facial deformation following orthognathic surgery for mandibular prognathism. The deformation is calculated using a model that assumes severe skeletal class III malocclusion. The possibilities and limitations of this method for clinical application are described. PMID- 1500953 TI - Cephalometric evaluation of crib therapy for cases of mixed dentition (open bite). AB - The effect of crib therapy for the treatment of cases of open bite was investigated. Extrusion of the lower and upper incisors and intrusion of the lower first molars were the most significant effects of the appliance. Intrusion of the lower molars resulted in decreased lower facial height. These findings were considered to result from the posterior tongue posture. Thus, the clockwise pattern of the mandibular complex was changed to a counter-clockwise pattern. PMID- 1500952 TI - A case of eosinophilic granuloma arising in the mandible. AB - Eosinophilic granuloma is a disease of the reticuloendothelial system and its pathogenesis is not yet completely clear. The histopathological findings are granulomatous proliferation of histiocytes accompanied by diffuse infiltration of eosinophils. We recently experienced a case of eosinophilic granuloma arising monostotically in the body of the mandible in the 76 [symbol: see text] region. There has been no local recurrence 17 months after surgical removal of the lesion. PMID- 1500954 TI - Clinical and immunological characteristics of patients with rheumatoid arthritis and periodontal disease. AB - Various clinical and immunological parameters were determined in patients with RA and patients with adult periodontitis. There were no significant differences between the two groups with regard to the number of missing teeth, although pocket depths and gingival inflammation scores were significantly increased in the periodontitis group (p less than 0.05). Salivary IgM levels were below the minimum detectable level in both groups, and no significant differences were evident between the two groups with regard to salivary IgG and IgA levels. However, serum IgG, IgA and IgM levels in RA patients were significantly higher than in periodontitis patients (p less than 0.05), indicating enhanced humoral immunity. The present findings suggest that RA patients are not a risk group for advanced periodontal problems in comparison with age- and sex-matched systemically healthy controls. PMID- 1500955 TI - Brain damage following subarachnoid hemorrhage: the imbalance between anti oxidant systems and lipid peroxidative processes. AB - We have studied the pattern of enzymatic antioxidant activities (Cu-Zn superoxide dismutase = SOD, Mn-SOD and glutathione peroxidase = GSH-Px) in brain cortex of rats subjected to experimental induction of subarachnoid hemorrhage (SAH), in order to discuss the modifications of antioxidant systems in relation to the development of lipid peroxidative processes occurring in brain cortex. Lipid peroxidation (quantified as TBRAs content) did not show significantly changes, when sham-operated and SAH rats were compared; meanwhile at 1 hour TBARs content shows an increasing trend both in sham-operated and hemorrhagic rats. The release of leukotriene C4, the major lipoxygenase metabolite, is significantly enhanced at 1, 6 and 48 hours after SAH induction. Cu-Zn SOD activity is significantly reduced at 6 and 48 hours after SAH induction; Mn-SOD activity is significantly affected at 1, 6 and 48 hours after the hemorrhage. GSH-Px activity is significantly reduced only in the late phase (48 hours) after SAH. The results of the present study suggests that: (a) in brain compartment a significant reduction of antioxidant enzymatic activities is related to the increasing trend of enzymatic lipid peroxidation; (b) antioxidant activities showed specific time dependent modifications: Cu-Zn and Mn SOD activities, which are specific scavengers of superoxide radicals, showed an early impairment, while GSH-Px activity is significantly reduced only after 48 hours; (c) the enhancement of enzymatic lipid peroxidation via the lipoxygenase pathway seems to play a primary role in brain response to SAH. These results should be considered the rationale for pharmacological treatment with antioxidant compounds for brain protection against detrimental effects of subarachnoid hemorrhage. PMID- 1500957 TI - Antiplatelet treatment after carotid endarterectomy: a pilot study. AB - The present study was undertaken in patients subjected to endarterectomy for extracranial carotid stenosis in order to verify the efficacy and the safety of medical treatment with indobufen (2-[4-(1-oxo-2-isoindolinyl)-phenyl] butyric acid), a drug which has been successfully used in the long-term treatment of cardiovascular ischemic diseases, and which showed a significant antiplatelet effect. One hundred thirty-eight patients entered into the study with previous diagnosis of cerebrovascular ischemic event within 3 months before surgery. Patients were treated after surgery with indobufen 400 mg/die/orally in the first 2 months after discharge and than 200 mg/die/orally. The planned duration of medical treatment was 24 months. Any patient interrupting the medical treatment for a cumulative period greater than 30 days/year was excluded from the analysis; the end points of the study were considered death and the occurrence of disabling stroke. Eleven patients were considered as dropped out because of treatment interruption. The operative (at 1 month after surgery) mortality rate was 0.79%. The cumulative operative mortality and morbidity rate was estimated in 2.37%. The mean follow-up period was 6 months and the cumulative mortality rate at 36 months was estimated in 7.14%. The cumulative risk/year of TIA or ischemic stroke is higher than the risk for myocardial infarction, but the long-term mortality rate mainly depends on the latter complication which occurred later. Treatment with indobufen after carotid surgery seems to be effective as far it was restricted to an homogeneous group of patients presenting symptomatic extracranial carotid disease. PMID- 1500956 TI - Clinicopathological experience with intraventricular neurocytomas. AB - Intraventricular neurocytoma is a rare clinicopathological entity that has been recently described. We are reporting our experience with four diagnosed cases and the previously reported cases from the available literature are reviewed. These neoplasms occur mainly in young adults, and their histological diagnosis is difficult on light microscope, because they are almost indistinguishable from oligodendrogliomas. Nevertheless, the presence of tumoral cells arranged around nucleus-free fibrillary zones, resembling the large rosettes of pineocytomas and the immunohistochemical demonstration of synaptophysin are useful data for the pathological diagnosis. This diagnosis is easy on electron microscope, because it demonstrates the neuronal nature of tumoral cells. Regarding prognosis, we have found increasing evidence that these tumors are associated with a favourable course after surgery, and at present there is no clear evidence of the usefulness of radiotherapy. PMID- 1500958 TI - EEG and the linear skull fractures. AB - The EEGs of 111 children under the age of 16, and 21 adults after a head injury with a linear skull fracture were reviewed. From our results it can be concluded that linear skull fractures do not add any significant abnormality or any variation to what is stated for EEGs of minimal to mild concussions. PMID- 1500959 TI - Case report and review of the literature: arachnoid cyst of the fourth ventricle presenting as a syndrome of normal pressure hydrocephalus. AB - The Authors report a case of 4th ventricular arachnoid cyst that presented clinically with the criteria of normal pressure hydrocephalus (NPH). Only a few cases of intraventricular arachnoid cyst have been recorded in the literature; the present case is the second reported case diagnosed as a syndrome of NPH. PMID- 1500960 TI - Cervico-medullary junction hemangioblastomas. Report of two cases and review of the literature. AB - Reporting two cases of dorsally located cervico-medullary hemangioblastomas the Authors discuss clinico-biological features, diagnosis and therapy of this vascular neoplasms, analyzing the cases reported in detail in the available literature. In this site the tumor has often an exophitic development, adhering more or less extensively to the posterior surface of medulla oblungata, where progressively creates a niche. Transient neurogenic arterial blood hypertension, by possible involvement of the dorsal nucleus of vagal nerve, together with the lack of postoperative respiratory disturbances constitute the main clinical features of differentiation with intraaxial hemangioblastomas of the brainstem. Actually MRI represents the radiological investigation of choice, even if angiography still plays an important role in the correct preoperative diagnosis of hemangioblastomas. The therapy of dorsally located cervico-medullary hemangioblastomas is the total removal of the lesion also in asymptomatic patients, being the late surgical results generally successful. PMID- 1500961 TI - A rare case of Toxocara canis arachnoidea. AB - The Authors present a case of Toxocara canis arachnoidea located in the cervical zone. The rarity of the case and the extreme rarity of the position are emphasized. In fact in medical literature there exists a description of only one similar case which was also observed by one of the authors. PMID- 1500962 TI - Establishing an oral health program for a long-term health care facility. PMID- 1500963 TI - In-office survey of curing light maintenance. PMID- 1500964 TI - The relationship of occlusion, parafunctional habits and recent life events to mandibular dysfunction in a non-patient population. AB - This study investigated the association between occlusion, oral habits and stress relative to the level of mandibular dysfunction in the total population and in specific diagnostic subgroups (normal, joint disorder, muscle disorder and joint/muscle disorder). A total of 269 nursing students were given a questionnaire and examination. The questionnaire included items to calculate an oral habit index and a social readjustment rating scale. The examination included items to calculate an occlusal index, two craniomandibular indices and a diagnostic criteria for specific subgroups. In the total population there was a positive association between mandibular dysfunction and three postulated risk factors. The total population was then divided into diagnostic subgroups. There was a positive association between the degree of mandibular dysfunction and parafunctional habits for normals, muscle disorders and joint/muscle disorders. There was a positive association between mandibular dysfunction and occlusion for normals only. Finally there was a positive association between mandibular dysfunction and stress for muscle disorders only. The results suggest that associations between postulated aetiologic factors and mandibular dysfunction vary depending on whether the subjects have a muscle and/or joint disorder. Since all associations were weak, other possible risk factors need to be investigated. PMID- 1500965 TI - Reinforcement of acrylic resin denture base material with metal or fibre strengtheners. AB - The effect of different metal and fibre strengtheners on the fracture resistance of polymethylmethacrylate was tested. Different types of commonly used metal wire and glass fibre, as well as carbon and aramid fibres, were used as strengtheners in test specimens. There were 21 groups, and each group contained 12 test specimens. Each metal strengthener had a beneficial effect on the fracture resistance of the polymethylmethacrylate (P less than 0.001-0.01). Some fibres, which were silanized for better adhesion, also had strengthening properties. PMID- 1500967 TI - Determining the accuracy of gypsum casts made from type IV dental stone. AB - A study was conducted to evaluate the accuracy of casts made in Type IV dental stone. The results indicate that all casts distort, but that significant differences exist between various brands of die stone. PMID- 1500966 TI - The clinical performance of a posterior composite resin restorative material, Heliomolar R.O.: 3-year report. AB - A posterior composite resin restorative material was evaluated over a 3-year period by means of a controlled clinical trial. A total of 52 composite resin restorations and 52 amalgam alloy restorations were included in this trial, and were examined with regard to marginal integrity, surface texture, anatomical form and proximal contact with adjacent teeth. There were no significant differences in clinical performance between test and control materials, which both gave good service over the period of evaluation. Only five restorations (one of amalgam and four of composite resin) failed during the trial. Plastic replica dies were used to support the clinical examinations of the restorations, and such dies were found to be helpful. PMID- 1500968 TI - Longitudinal study on torque transmitted from a denture base to abutment tooth of a distal extension removable partial denture with circumferential clasps. AB - Not only forces but also torque exerted on abutment teeth are important factors for planning the construction of distal extension removable partial dentures. The purpose of this study was to make longitudinal analysis of torque transmitted from denture base to a direct abutment tooth of these dentures with circumferential clasps. The results are summarized as follows: (i) Vertical Max. MT (maximal mean value of torque) was decreased and became constant after one or one and half months of the insertion of new dentures. (ii) Lateral Max. MT in one subject was changed from the lingual direction to the buccal direction while in another subject it was constant. (iii) In the vertical direction, there were no remarkable differences of Max. MT and Ave. T (average value of torque) between subjects. Max. MT was 5-10 x 10(-3) kgm-1 in the downward. Ave. T was 2-3 x 10( 3) kgm ss-1 in the downward and 0.3 x 10(-3) kgm ss-1 in the upward. (iv) In the lateral direction, there were considerable differences of Max. MT and Ave. T between subjects. Max. MT was less than 20 x 10(-3) kgm. Ave. MT was 2-8 x 10(-3) kgm ss-1. PMID- 1500969 TI - Reproducibility of temporomandibular joint vibrations (electrovibratography). AB - Surface electrovibratographic (EVG) recordings were obtained from the temporomandibular joints (TMJ) of clinically normal subjects (absence of TMJ sounds) and clinically abnormal subjects (presence of TMJ sounds). As examined through single factor analyses of variance and coefficients of intraclass correlation, the EVG recordings showed excellent reproducibility. The analyses showed also that, in comparison with clinically normal TMJs, the vibrations of clinically abnormal TMJs had higher median (+79%) and peak (+137%) frequencies, higher peak amplitudes (+740%), and higher intensities as expressed through the estimated total energy contents (+1843%) and the integrals (+1215%) of power spectrum density functions. PMID- 1500970 TI - Microleakage studies comparing a one-visit indirect composite inlay system and a direct composite restorative technique. AB - Problems related to leakage have been observed with direct-filled composite restorations. The development of indirect system of fabrication followed by cementation should theoretically reduce this phenomenon. The present study compares the leakage around directly placed composites with composite inlays prepared by a surgery-based system. The results indicate that the amount of leakage is reduced with the inlay system, but that it is not eliminated. PMID- 1500971 TI - A preliminary study of manducatory behaviour influenced by stress and dental occlusion. AB - Stress and dental occlusion often are incriminated as causes of dysfunction of the manducatory system. How and in what degree these two factors came through has not yet been clearly worked out. Our study is carried out on a group of rats presenting one or both of these two factors and we proposed to examine the duration and frequency of some components of their behaviour--intake of solid food and grooming, to detect some possible perturbations on manducatory behaviour caused by stress and/or occlusal interference. Our study shows that stress induced by emotion or occlusal interference will change the microstructure of behaviour rather than the global component in itself. This implies that we must find a clear definition of the different types of microstructure to find out which ones are changed by the two incriminating factors and which part of the behaviour component will remain stable. PMID- 1500972 TI - Masticatory function in hemimandibulectomy patients. AB - Surgical resection of a segment or loss of continuity of the mandible can adversely affect most of the structures essential for mastication. Five subjects who had hemimandibular resections for cure of squamous cell carcinoma were studied. Masticatory function tests were conducted pre- and post-surgery and post prosthetic rehabilitation. A 0.5-g Frito corn chip served as the test food, and a sieve analysis was used to evaluate swallowing threshold and masticatory performance. Ten controls were studied in order to determine corresponding normative scores. Post-surgery results indicate that the extent of mandibular resection and loss of continuity tend to decrease masticatory function. The time required to perform the mastication test, and the number of strokes required to achieve swallowing threshold were increased. Prosthetic rehabilitation did improve masticatory function in some patients. Loss of mandibular continuity may not be an absolute predictor of decreased masticatory function. PMID- 1500973 TI - Digital imaging techniques for dental alloy castability quantification. AB - In this study, mesh monitors cast from experimental compositions of a Ni-Cr-Be alloy are evaluated by the application of image analysis techniques. Castability values obtained by this method are then contrasted with those from three commonly employed manual counting procedures. While castability values obtained by all methods reflect the effect of compositional variations, a comparison of results with respect to evaluation method indicates that the image analysis technique consistently yields higher castability values, especially evident in the poorly casting groups. The apparent explanation for these observed differences is that with imaging, segments that are partially cast to varying degrees are not arbitrarily eliminated from the data, as is the usual practice in manual counting methods; therefore, castability values obtained by using the imaging technique will very closely reflect an actual alloy volume of each cast monitor. PMID- 1500974 TI - Metabolic and biochemical status of articular cartilage following cryopreservation and transplantation: a rabbit model. AB - To determine the fate of transplanted cryopreserved articular cartilage, an animal model employing the proximal humerus in the rabbit has been developed. Previous studies have been hindered by problems of postoperative joint instability, secondary injury due to immobilization, and paucity of cartilage for analysis. This experiment demonstrates the survival and function of transplanted cartilage by quantitative assessment of metabolic and biochemical parameters. Forty-five New Zealand white rabbits underwent transplantation of the right proximal humerus. In 29 animals, the proximal half of the humerus was resected and replaced by a cryopreserved osteoarticular allograft. Autograft procedures were carried out in the remaining animals. Following sacrifice at 3, 6, 9, and 12 months postoperatively, articular cartilage was analyzed for gross appearance, collagen synthesis, proteoglycan synthesis, and water, hydroxyproline, hexosamine, and hexuronic acid contents. The results indicate that the cryopreserved osteoarticular allografts retained their metabolic and biochemical integrity and behaved as viable and biologically functional units 1 year postoperatively. PMID- 1500975 TI - Local stimulation of proteoglycan synthesis in articular cartilage explants by dynamic compression in vitro. AB - Cultured bovine articular cartilage was subjected to 50 ms, 0.5-1.0 MPa compressions repeated at intervals of 2-60 s for 1.5 h and simultaneously labeled with 35SO4. The compression was delivered with a 4-mm-diameter nonporous loading head on an 8-mm-diameter cartilage explant. This method created directly compressed (central) and uncompressed (border) areas within the tissue. Analysis of the whole explant under a 0.5 MPa load showed significantly increased 35SO4 incorporation by compression repeated at 2- and 4-s but not at 20- and 60-s intervals. When the incorporation was studied separately in the border and central areas, a statistically significant stimulation was noticed in the central area with a 4-s cycle, while the border area was stimulated with a 2-s cycle. Autoradiography of the central area showed that the stimulation with 0.5 MPa and a 4-s cycle occurred through the whole depth of the cartilage, while raising the pressure to 1 MPa or the frequency to 2 s reduced the stimulation, particularly in the superficial cartilage. In the border area the stimulation with 0.5 MPa and a 2-s cycle was noted in the superficial zone only. The stimulation of proteoglycan synthesis is thus limited to certain loading frequencies and pressures and occurs in specific areas under and around the loaded site. Its rapid appearance suggests enhanced glycosylation or sulfation of core proteins or enhanced speed of posttranslational processing. PMID- 1500977 TI - The dermatan sulfate proteoglycans of the adult human meniscus. AB - The dermatan sulfate proteoglycans decorin and biglycan were extracted from pooled adult human menisci with 4 M guanidinium chloride and purified by successive cesium chloride density gradient centrifugation, ion exchange chromatography, and gel filtration. A final yield of about 2 mg of dermatan sulfate proteoglycan per gram of wet tissue was obtained. The proteoglycan is predominantly decorin with some biglycan, and the dermatan sulfate chains contain about 70% of their uronic acid residues as iduronate and possess about three times as much 4-sulfation as 6-sulfation of their N-acetylgalactosamine residues. On gel filtration under associative conditions, about half of the proteoglycan exhibits self-association. This includes most of the biglycan but also a substantial proportion of decorin. The molecules that show self-association appear to have longer dermatan sulfate chains, though there is no apparent difference in their overall composition. The predominance of decorin in the adult meniscus and its ability to interact both with itself and collagen fibrils is compatible with a role in maintaining tissue integrity and strength. PMID- 1500976 TI - Link protein shows species variation in its susceptibility to proteolysis. AB - Human cartilage link protein exists as three native components, while equine, bovine, and porcine cartilage link protein exist as two and Swarm rat chondrosarcoma link protein exists as only one component. These nonhuman link protein components represent intact protein structures, and there is little evidence for proteolytically modified forms in nonhuman tissues. In human cartilage, the proteolytic production of modified link proteins increases with age, whereas high amounts of such products were not seen in the nonhuman tissues. However, the small amounts of link protein fragments that were observed in the nonhuman cartilages were of a similar size to their human counterparts. On digestion of human proteoglycan aggregate with stromelysin, rapid modification of the link protein components occurred, whereas the aggregates from nonhuman cartilages showed incomplete cleavage of their link protein components. The relative resistance of nonhuman link protein to stromelysin may in part be due to a unique amino acid substitution present near the enzymic cleave site. PMID- 1500978 TI - [99mTc]diphosphonate uptake and hemodynamics in experimental arthritis: effect of naproxen in the canine carrageenan injection model. AB - The impact of naproxen treatment on juxta-articular hemodynamics and bone metabolism in experimental juvenile arthritis was studied in the articular carrageenan injection model. Unilateral gonarthritis was induced for 12 weeks in eight dogs receiving naproxen (dosage, 2 mg/kg) and eight controls. Regional blood flow was assessed by the microsphere method, plasma volume by the distribution space of [125I]fibrinogen, and bone metabolism by the 2-h uptake of [99mTc]diphosphonate ([99mTc]DPD). Synovial effusion was less prominent with naproxen treatment as judged by joint fluid volume and pressure. Naproxen reduced the arthritic capsular hyperemia, almost normalized a severe blood flow increase in patella and both juxta-articular epiphyses, ameliorated an expansion of plasma volume in the patella and the distal femoral epiphysis, and normalized an increased [99mTc]DPD uptake in subchondral femoral bone and the tibial cortex. Significantly increased arteriovenous shunting in the arthritic extremity was unaffected by naproxen. The study suggests that long-term cyclooxygenase inhibition offers protection against hemodynamic and metabolic changes in juxta articular bone secondary to synovial inflammation. PMID- 1500979 TI - The functional recovery of peripheral nerves following defined acute crush injuries. AB - This study evaluates the effect of crushing load on functional recovery of the sciatic nerve. Male Sprague-Dawley rats were divided into five groups: sham operation, resected sciatic nerve, and 100 g (13 mm Hg/mm2), 500 g (50 mm Hg/mm2), and 15,000 g (1,000 mm Hg/mm2) of sciatic crush load (groups 1-5). In groups 3-5, a 5-mm segment of sciatic nerve was crushed for 10 min using a specially designed crushing device. Motor functional recovery was assessed from hind-limb walking tracks by calculating a sciatic functional index. There was no detectable functional deficit in the group receiving sham operations, while the resected sciatic nerve group exhibited complete dysfunction for the full duration of the experiment. All groups subjected to crush exhibited an initial deficit that gradually recovered to normal by day 14 (100-g crush), day 39 (500-g crush), and day 53 (15,000-g crush). Histological changes were also related to the initial crushing load and the length of the recovery period. Results indicate that the crushing device described is able to administer an adjustable, defined crush injury to the rat sciatic nerve, and that the functional deficit resulting from such an injury can be easily monitored with a sciatic functional index. The rate of recovery of crushed nerves was directly related to the initial load. All crushed nerves recovered in this experiment, even after the application of a 15,000-g load for 10 min. PMID- 1500980 TI - A longitudinal study of the matrix changes induced in the intervertebral disc by surgical damage to the annulus fibrosus. AB - A 5 x 5-mm anterolateral incision was made in the annulus fibrosus (AF) of lumbar discs of 16 sheep; four animals of similar age not operated on were used as controls. The experimental animals were sacrificed 2, 4, 6, 8, 12, and 18 months postoperatively (PO), and the incised and adjacent lumbar discs were collected. Discs were dissected into four zones: AF (zones 1 and 2) and nucleus pulposus (NP) (zones 3 and 4) corresponding to the half of the AF in which the cut was made and its opposite half, and the complementary halves of the NP. Each zone was analyzed for moisture, proteoglycan (PG), collagen, and noncollagenous protein (NCP) content. The PG extractability, aggregation, and hydrodynamic size were also examined. The NP of injured discs showed a significant loss of PGs and collagen 8 months PO, but NCP levels increased. In the incised discs, PG aggregation initially declined but recovered to within control values 6-8 months PO. The NP of discs adjacent to the incised disc also showed time-dependent changes in matrix components that included loss of collagen and PG; however, the AF matrix remained essentially uneffected. Double immunodiffusion studies indicated that a sizeable proportion of the NCPs present in the injured discs (but not the adjacent lumbar discs) were derived from serum. PMID- 1500981 TI - Trunk muscle cocontraction: the effects of moment direction and moment magnitude. AB - This study investigated the cocontraction of eight trunk muscles during the application of asymmetric loads to the torso. External moments of 10, 20, 30, 40, and 50 Nm were applied to the torso via a harness system. The direction of the applied moment was varied by 30 degrees increments to the subjects' right side between the sagittally symmetric orientations front and rear. Electromyographic (EMG) data from the left and right latissimus dorsi, erector spinae, external oblique, and rectus abdominus were collected from 10 subjects. The normalized EMG data were tested using multivariate and univariate analyses of variance procedures. These analyses showed significant interactions between the moment magnitude and the moment direction for seven of the eight muscles. Most of the interactions could be characterized as due to changes in muscle recruitment with changes in the direction of the external moment. Analysis of the relative activation levels, which were computed for each combination of moment magnitude and direction, indicated large changes in muscle recruitment due to asymmetry, but only small adjustments in the relative activation levels due to increased moment magnitude. PMID- 1500982 TI - Cross talk in surface electromyograms of human hamstring muscles. AB - Signals generated from muscles other than the muscle(s) of interest (cross talk) can confound the interpretation of surface electromyograms (EMGs). In this study, the amount of cross talk in surface EMGs of human hamstring muscles was estimated using a protocol in which the quadriceps femoris was electrically stimulated via the femoral nerve. EMGs were recorded from the vastus lateralis and the medial and lateral hamstring muscle groups. The amplitude of the EMG response of the vastus lateralis to electrical stimulation was adjusted to match that of its maximum voluntary effort (MVE) under isometric conditions. Subsequent power density spectrum analysis showed that the median frequencies of the signals generated by electrical stimulation and MVE were not significantly different. In conventional bipolar recordings, cross talk in lateral hamstring EMGs averaged 17.1% MVE and in medial hamstring EMGs 11.3% MVE (average-rectified values). The double differential technique significantly reduced cross talk to 7.6% MVE for the lateral hamstrings, and to 4.2% MVE for the medial hamstrings. The double differential technique appears to be more selective than the bipolar technique when recording EMGs from muscles with highly active neighbors and thus should be used in such situations. Software simulations of the double differential technique also appear to be more selective than the bipolar technique and may be used when the number of amplifiers available is limited. PMID- 1500983 TI - A comparative analysis of streaming potentials in vivo and in vitro. AB - Streaming potentials (SPs) measured in vivo at a specific site on intact cortical bone (canine tibia) have been compared with measurements from the same site in vitro, tested as an excised bone strip soaked in Hank's balanced salt solution. The amplitude of SPs per periosteal strain in vitro was larger in 13 tibias than in vivo (by an average x6.5 at 1 Hz), but values per transcortical strain difference were similar. In vitro, SP magnitudes rose more sharply to an asymptotic value as a function of bending frequency than did in vivo signals, possibly because of a difference in the internal state of canaliculi and/or Haversian systems. Similarly, SP response to step-loading decreased to zero more slowly with time in vitro than in vivo. Difficulties encountered in preliminary measurements due to electrical shunting through electrolyte and soft tissues suggest the need for caution in using both in vivo and in vitro SP measurements to extrapolate to electric field strengths on the cellular level. PMID- 1500984 TI - Chemotherapy and surgery in a murine osteosarcoma. AB - Surgical and chemotherapeutic effects on pulmonary metastatic disease were evaluated in the MGH-OGS murine osteosarcoma. The tumor responded to three sequential injections of doxorubicin with prolonged growth delay but cisplatin administration (although given in doses sufficient to cause weight loss and significant mortality) was not effective in controlling local disease progression. Using a protocol with three injections of doxorubicin (0.006 mg/g of body weight), it was observed that disease-free survival was enhanced when one of the three doses of doxorubicin was given at the time of surgery (perioperatively). By marginally resecting the primary tumor and permitting its regrowth, a model was developed with recurrent primary and metastatic disease present simultaneously. It was observed in this model that amputation or resection of the recurrent primary lesion resulted in pulmonary metastatic growth acceleration. Using this recurrent primary tumor model, doxorubicin's effect on pulmonary metastatic lesions was enhanced when the drug was given at the time of amputation. PMID- 1500985 TI - Bone formation near direct current electrodes with and without motion. AB - The osteogenesis induced in the medullary canal of rabbits by the implantation of moving and stationary wire electrodes was studied with and without the simultaneous application of 20-microA constant direct cathodic current. After 3 weeks, the formation of new trabecular bone in the canal was studied and measured microscopically. Electrically stimulated osteogenesis was not observed at stationary electrodes. As in previous studies with this model, a movable electrode alone stimulated new bone formation whose area was 7-10% of the canal area. The amount of this bone was not statistically increased by the addition of cathode current. Movable, electrically active cathodes were associated, however, with fluid-filled spaces incorporated within the new trabecular bone. When mechanical stimuli were controlled, we were not able to demonstrate that the direct current stainless steel cathode acts either as an inducer or a substantial enhancer of medullary osteogenesis. PMID- 1500986 TI - A comparison of cortical strain after cemented and press-fit proximal and distal femoral replacement. AB - Proximal and distal femoral replacements with intramedullary stems are usually cemented in place but frequently show severe bone remodeling changes in the long term, which can contribute to a loosening process. The remodeling is likely to be associated with stress and strain distribution. This study compared the strain patterns, particularly the maximum principal strains, between cemented and press fit components in five cadaveric femurs by using a photoelastic coating technique. The specimens were loaded with 2,000 N in the sequences of intact femur and press-fit and cemented stems. On the medial side of the bone for proximal femoral replacements, the strain values for the press-fit stems on the proximal, middle, and distal regions were 73 +/- 11%, 78 +/- 15%, and 80 +/- 15% of normal, respectively, but for the cemented stems they were 53 +/- 15%, 57 +/- 19%, and 60 +/- 20%. The differences were statistically significant (p less than 0.05). On the lateral side, the overall strain values for the press-fit stem were higher than those for the cemented stem, but the differences were not statistically significant (p greater than 0.05). On the medial side of the distal femoral replacement, the strain values for the press-fit stems in the proximal and middle regions were significantly closer to normal than for the cemented stems. Because the press-fit femoral stems (both the proximal and distal replacement) transferred closer to normal strains than the cemented stems, less adverse bone remodeling may be expected, which could be reflected in increased longevity. PMID- 1500988 TI - Caring, competency, certification: the hallmarks of intravenous nurses. PMID- 1500987 TI - Chief executive officer's report. Intravenous Nurses Society. PMID- 1500989 TI - Communication: the sharing of knowledge. PMID- 1500990 TI - Home infusion service delivery system model: a conceptual framework for family centered care in pediatric home care delivery. AB - The Home Infusion Service Delivery System model is presented as a conceptual framework for the delivery of pediatric home care. This bicycle-shaped model provides important insights into the interrelationships of available resources for parents seeking home health care for their child. The model is based on nine key elements of family-centered care. Discussions of the model identify the roles and relationships among the family system, four interdependent service delivery systems, the physician, and a total quality management program that coordinates the health care delivery for the child. Examples focus on the delivery of pediatric home infusion therapy. By supporting the family as the primary care giver, this model provides a better fit between consumer need and service delivery. PMID- 1500991 TI - AIDS--pharmacologic update. AB - No one discounts the cruel nature of the Acquired Immunodeficiency Syndrome epidemic or the pain and devastation left by the virus that brings a lingering death to people in the prime of life. And no one dismisses the horrifying surge in the number of cases over the past decade. In 1981, 189 cases of AIDS were reported to the Centers for Disease Control; in 1990, 43,339 cases were reported. Research and technological advances have resulted in advanced treatment modalities aimed at symptomatic treatment of the disease process itself, opportunistic infections associated with the disease, and possibly prevention. These issues are addressed in this update. PMID- 1500992 TI - Patients' preference regarding portable pumps. AB - The growing number of home parenteral nutrition patients has encouraged the development of portable infusion pumps. The authors found that the individual who meets the criteria for home therapy is also the same individual who welcomes independence. The portable pump further enabled these individuals, who have already undergone a major lifestyle change, to achieve the desired independence. Twenty-three home parenteral nutrition patients were surveyed regarding pump satisfaction and operation. The distinct psychological advantage provided was the final motivating factor. PMID- 1500993 TI - The value physicians place on nursing certification: the Journal speaks with George Ritter, MD. PMID- 1500994 TI - Intravenous therapy education in associate degree nursing programs. AB - Questionnaires were sent to 250 National League of Nursing-accredited associate degree registered nursing programs in the continental United States to determine what components of intravenous therapy were being taught, how these components were being taught, and where in the curriculum these components were being taught. The questionnaire also included questions that could provide insight into intervening variables such as support from clinical facilities and administrative support. PMID- 1500995 TI - Chemical dependency: recognition and intervention. PMID- 1500996 TI - An asymptomatic white patch of lateral tongue mucosa. PMID- 1500997 TI - Flexible spending arrangements or how to give your employees a raise without using cash. PMID- 1500998 TI - Endoscopic laser ablation of obstructing congenital duodenal webs in the newborn: a case report of limited success with criteria for patient selection. AB - Standard approaches to intrinsic obstructing duodenal lesions in the newborn include laparotomy with enteroenterostomy, bypassing the obstruction, or duoduodenotomy with excision. The advent of improved pediatric flexible fiberoptic endoscopes and fiberoptic laser technology makes endoscopic ablation of duodenal webs and windsocks in the newborn possible. PMID- 1500999 TI - Surgical therapy and long-term follow-up of childhood hereditary pancreatitis. AB - Treatment and a 15-year follow-up survey of 42 patients with hereditary pancreatitis (HP) were compared with 28 patients with idiopathic recurrent pancreatitis (RP) of childhood. There was no difference between the two groups except for pancreatic ductal dilatation and stones in patients with HP. Longitudinal pancreaticojejunostomy (20) or resection and drainage procedures (7) were more commonly required in patients with HP than RP (55% v 14%). There was no surgical mortality. Postoperatively, immediate and complete relief of symptoms was obtained in 43% of patients with HP and 25% of patients with RP. In the remainder, recurrent attacks of pancreatitis abated over 2 years such that 81% of the surgical patients were in good or excellent health. Occasional symptoms persisted in 52% of HP patients and 25% of RP patients. Of the 20 patients with HP or RP undergoing longitudinal pancreaticojejunostomy extending from the head to the tail, 75% were symptom-free on follow-up. However, 3 of 6 patients with poor results had also undergone this procedure. At long-term follow-up of patients who did not undergo operation, 75% of HP patients and 90% of RP patients reported excellent or good health despite the persistent symptoms in 68% and 42%, respectively. Surgery for childhood HP is dependent on the complications present. Longitudinal pancreaticojejunostomy is beneficial for ductal dilatation and associated pseudocysts or pancreatic ascites. The performance of this procedure in the absence of consistent pancreatic duct dilatation will give poor results. Patients without ductal dilatation and the majority of patients with RP may eventually lead near normal lives without resorting to surgery.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1501000 TI - Quantitation of transplanted hepatic mass necessary to cure the Gunn rat model of hyperbilirubinemia. AB - The minimal hepatic mass necessary to reverse the metabolic defect of unconjugated hyperbilirubinemia in the rat model of Crigler-Najjar type I deficiency was determined using heterotopic (auxiliary) partial liver transplantation (HLT) and orthotopic liver transplantation (OLT). In HLT, the donor graft consisted of the right upper and/or right lower hepatic lobe(s) depending on the final mass of liver tissue desired for transplantation. The mass of the donor graft ranged from 12% to 23% of the whole organ (n = 12). The serum unconjugated bilirubin levels decreased quickly after HLT from a preoperative value of 8.98 +/- 0.34 mg/dL to 0.63 +/- 0.11 mg/dL in 24 hours, which was similar to OLT in which the levels decreased from a preoperative value of 8.20 +/ 0.44 mg/dL to 0.24 +/- 0.07 mg/dL in 24 hours. Conjugated bilirubin was excreted from the graft liver shortly after OLT and also from both the host and graft livers after HLT. This study demonstrates that using as little as 12% of the whole liver mass in HLT reduces serum bilirubin significantly in 24 hours in a fashion similar to whole-organ OLT. The clinical application of alternative therapies to whole-organ OLT such as HLT or hepatocyte transplantation may provide sufficient replacement therapy in metabolic disease. PMID- 1501001 TI - Coagulation plasma factor levels are early indicators of graft nonfunction following liver transplantation in children. AB - Following liver transplantation, the decision to retransplant in cases in which graft function is marginal must be taken early. Plasma coagulation factor monitoring was evaluated as an early predictor of graft failure requiring retransplantation in the first posttransplant week. Plasma levels of fibrinogen, factors V, VII, VIII, IX, antithrombin III, protein C, and plasminogen were measured in all patients at 0, 12, 24, 48, 72, 96, and 120 hours posttransplant in 46 patients who received 56 grafts and results were compared between livers that failed early (group 1) and those that functioned adequately (group 2). Six grafts were included in group 1: one patient died before retransplantation, four were retransplanted once, and one patient was retransplanted twice. Three grafts had primary nonfunction (PNF), 2 had obstructed portal veins, and 1 had a long period of warm ischemia during the initial transplant. In group 1, plasma levels of factor V were significantly lower than in group 2 at 24, 48, and 72 hours posttransplant (21.2% +/- 14.2%, 12.4% +/- 4.5%, and 13.0% +/- 5.0% v 39.1% +/- 23.9%, 48.8% +/- 31.9%, and 60.9% +/- 25.9%; P less than .05, P less than .01, and P less than .005, respectively). Similarly, plasma levels of factor VII were significantly lower in group 1 over the same period of time (7.3% +/- 2.7%, 4.2% +/- 1.8%, and 4.7% +/- 2.5% v 27.4% +/- 17.1%, 34.1% +/- 21.6%, and 34.8% +/- 18.6%, respectively; P less than .005).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1501002 TI - Cross-species transplantation: NK cell number and function are normal in fully xenogeneic chimeras (rat----mouse). AB - When untreated F344 rat bone marrow is transplanted into B10 mouse recipients conditioned with total body irradiation, stable fully xenogeneic chimerism (rat-- -mouse) results. Chimeras are specifically tolerant to the donor strain of rat, survival is excellent (greater than 80% at 8 months), and all stem-cell-derived lineages are produced by the rat stem cell. We have previously demonstrated normal function of T-lymphocytes in these chimeras, but have not examined the immune function of natural killer (NK) cells present. Because NK cells play a critical role in immune surveillance, absence of function could result in a serious immunodeficiency state. We present data here to suggest that rat NK cells that have developed in a mouse stromal environment are normal in function as well as number. In all fully xenogeneic chimeras tested from 8 weeks to 8 months following bone marrow transplantation, NK cells were present at a normal level (10% to 16%). NK cells function in these chimeras, as tested by spontaneous lysis of YAC tumor cell targets, was normal or superior to normal F344 rat and B10 mouse NK cells. PMID- 1501003 TI - Intrahepatic hepatocyte transplantation following subtotal hepatectomy in the recipient: a possible model in the treatment of hepatic enzyme deficiency. AB - Orthotopic liver transplantation as treatment for hereditary enzyme deficiencies in the absence of cirrhosis suffers from significant operative risks, complications, and donor shortages. Transplantation of isolated hepatocytes (HTX) may offer opportunities for the treatment of these diseases and retain the recipient liver. Hepatocytes transplanted into the portal vein, spleen, or omentum lack an ideal growing environment for cell proliferation and maintenance. Therefore, we investigated a method combining 75% recipient hepatectomy with direct injection of hepatocytes into the remaining 25% of liver parenchyma to provide proliferative stimuli and a stable environment during and following liver regeneration. Recipient Gunn rats (glucuronyltransferase deficiency and hyperbilirubinemia) underwent hepatectomy before HTX by direct injection of 10(7) isolated hepatocytes into the remaining parenchyma. Inbred male Wistar and Gunn rats were used as normal and control hepatocyte donors and saline injection served as a sham transplant control. Isolation of donor hepatocytes was performed with a two-step collagenase digestive method (Seglen) with cell viability of 85% to 95%. Liver regeneration was complete by 2 weeks posttransplant. Four weeks following HTX, total serum bilirubin and qualitative bile analysis were performed. A significant decrease in total serum bilirubin levels was observed in Gunn rats receiving Wistar hepatocytes compared with those receiving Gunn hepatocytes and saline control. Bile analysis from HTX rats demonstrated a normal pattern containing bilirubin monoglucuronides and diglucuronides (conjugated bilirubin) in the rats receiving Wistar hepatocytes, whereas the control group receiving Gunn hepatocytes or saline injection demonstrated only unconjugated bilirubin. No differences in histological appearance were noted between groups.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1501004 TI - Serum visceral protein levels reflect protein-calorie repletion in neonates recovering from major surgery. AB - Protein catabolism resulting from acute metabolic stress causes significant postoperative decreases in visceral proteins, including albumin (Alb) and prealbumin (PA). Although clinical trials have suggested an advantage of PA over Alb in monitoring the visceral protein response to nutritional supplementation following surgery, the capability of the neonate to generate such a response has yet to be evaluated. Therefore, this study was undertaken to determine if PA is superior to Alb in assessing postoperative repletion of the visceral protein pool in neonates. Serum Alb and PA levels were measured and energy balance (EB) and protein intake (PI) were recorded in 10 neonates less than 48 hours after major surgery and again following 4 consecutive days of positive EB. Resting energy expenditure (REE) was measured using indirect calorimetric methodology. Mean PI (g/kg/d) was lower (0.78 +/- 0.78) and mean EB (kcal/kg/d) was negative (-2.92 +/ 10.05) less than 48 hours postoperatively compared with mean PI (2.52 +/- 0.57; P = .0006) after 4 consecutive days of positive EB (34.84 +/- 16.5; P = .0004). Mean percent change (mean% delta) from negative EB to positive EB was significantly greater for PA (100%; P = .0002) as compared with Alb (18.5%). These data appear to support the conclusion that serial serum PA levels are superior to Alb to monitor the visceral protein response to nutritional supplementation in neonates following surgery. PMID- 1501005 TI - Intestinal villus microcirculatory response to hemorrhage in adult and immature rats. AB - The response of the villus microcirculation to moderate hemorrhage was compared in adult and immature rats. As an estimate of villus blood flow, flux of red blood cells through the terminal arteriole loop at the villus tip was quantified in vivo using fluorescence epilumination videomicroscopy. Baseline red blood cell flux and mean arterial pressure (MAP) of immature rats (973 cells/s, 84 mm Hg) were significantly less than that of adults (1,435 cells/s, 131 mm Hg). Following hemorrhage of 30% of estimated blood volume, MAP of immature rats was still 24% less than that of adults; however, villus flux was not significantly different (578 cells/s immature, 640 cells/s adult; P = .63). Thus, as indicated by changes in villus flux, immature rats do not appear to be more susceptible to acute intestinal blood flow reduction induced by a single moderate hemorrhage. Immaturity of villus microvascular anatomy and of intestinal vasoregulatory mechanisms may account for the differential response. PMID- 1501006 TI - Increased mucosal permeability after intestinal ischemia-reperfusion injury is mediated by local tissue factors. AB - Subclinical intestinal ischemia-reperfusion injury (IRI) causes an increase in mucosal permeability and may represent an early event in the pathogenesis of necrotizing enterocolitis. The present study was undertaken to determine whether these changes are mediated by local or systemic factors. In 6-week-old weanling rats, the ileum was divided into two isolated loops with separate vascular supplies. The mesentery of the proximal loop was occluded for 30 minutes, following which the bowel was reperfused; permeability to 51Cr EDTA was then assessed in the distal loop 30 minutes after reperfusion. In control groups, the distal loop was subjected to 30-minute IRI ("positive" control) or 30-minute sham operation ("negative" control). Permeability in the distal loop was increased only with IRI to the distal bowel (15.4 +/- 3 counts/min/standard), and not with IRI to the proximal bowel (5.1 +/- 1) or with sham operation (8.5 +/- 2). To determine whether a mild "priming" injury might be necessary for systemic factors to have an effect, the distal loop was subjected to 2-minute IRI and the proximal to 30-minute IRI or sham. Permeability was not increased in the distal loop in either of these groups (5.7 +/- 1 and 7.8 +/- 2, respectively). Thirty-minute IRI in the proximal loop did not increase permeability in the distal loop, with or without a priming injury. Only direct IRI in the distal loop resulted in a significant increase in permeability. We conclude that the permeability changes in this model are mediated through local tissue effects, rather than by systemic factors. PMID- 1501007 TI - Unique characteristics of the neonatal intestinal mucosal barrier. AB - The purpose of this study was to compare the newborn and weanling intestinal mucosa to determine differences in: (1) the electrophysiologic characteristics of the mucosal barrier; (2) the effects of glutamine supplementation on these physiological characteristics; and (3) transmucosal bacterial passage. The Ussing chamber was used to study ileal mucosa from newborn (1 to 4 days old) and weanling (21 days old) piglets. After the seromuscularis was stripped off the bowel wall, the mucosa was mounted in the chamber and perfused with Hanks Balanced Salt Solution (HBSS) or HBSS + 20 mmol/L of glutamine. Following initial stabilization, potential difference (PD) and resistance (R) were measured at 30 minute intervals for 2 hours. Transmucosal bacterial passage was measured by quantitative cultures of the mucosal and serosal reservoirs obtained 2 hours after adding 10(8) E coli C-25 to the mucosal reservoir. Six groups of membranes were studied: (1) newborn and HBSS; (2) weanling and HBSS; (3) newborn and HBSS + glutamine; (4) weanling and HBSS + glutamine; (5) newborn - HBSS + glutamine + E coli; and (6) weanling - HBSS + glutamine + E coli. Newborn ileal mucosa had significantly lower PD and R compared with weanling at all time points. Glutamine led to a significant increase in PD in both newborn and weanling. Newborn mucosa had a significantly increased incidence of transmucosal bacterial passage (4/7) compared with weanling (0/10). These findings suggest that: (1) newborn mucosal barrier has uniquely different electrophysiologic characteristics; (2) glutamine improves the metabolic activity as measured by PD in both newborn and weanling; and (3) the newborn mucosal barrier allows increased transmucosal passage of bacteria. PMID- 1501008 TI - The role of lymphatics in the pathogenesis of pneumatosis in experimental bowel ischemia. AB - Twelve spontaneously delivered, normally suckled, small-for-gestational-age (weighing 756 to 1,213 g) neonatal piglets were used to assess the role of the mesenteric vasculature in the pathogenesis of neonatal necrotizing enterocolitis (NEC) by producing intestinal ischemia. Component vessels (arteries, veins, lymphatics) of the mesenteric vascular arcades were variously occluded by ligation for 48 hours. Nine adjacent vessels of the same type or nine adjacent combinations of vessels were occluded in piglets 12 to 18 hours postpartum. Arterial plus lymphatic ligation induced lesions showing the complete histopathological spectrum of NEC (mucosal stripping, hemorrhage, submucosal disruption and destruction, full-thickness necrosis, inflammatory infiltration) including pneumatosis intestinalis. Two of the lowest birth weight animals produced complete NEC in response to lymphatic ligation alone. A condition consistent with "prepneumatosis" was found when lymphatics only were ligated. The distended lymphatic vessels in the submucosa resembled pneumatosis with reference to shape size and distribution, but contained milk-derived lipids, some proteins and lymph but no gas. Arterial ligation alone induced NEC-like lesions without pneumatosis. Venous ligation alone induced minor congestive/hemorrhagic lesions. Pneumatosis appears to originate in the lymphatic vessels of the submucosa in this experimental model of NEC. Lymphatic occlusion alone can cause complete NEC in very SGA neonatal piglets. Arterial plus lymphatic occlusion produces a unique combination of specific pathology resembling human NEC. PMID- 1501009 TI - Outcome and intestinal adaptation in neonatal short-bowel syndrome. AB - We reviewed 52 consecutive patients with short-bowel syndrome (SBS) treated with long-term parenteral nutrition (PN) from 1978 through 1990. The SBS etiologies included necrotizing enterocolitis (NEC) in 26 patients (50%), abdominal wall defects in 11 (22%), jejunoileal atresia in 6 (12%), midgut volvulus in 4 (8%), Hirschsprung's disease in 3 (6%), and segmental volvulus and cloacal exstrophy in 1 (2%) each. The average initial small bowel length was 48.1 cm, and only 31% of the patients retained an ileocecal valve (ICV). The mean duration of PN therapy was 16.6 months, and 39 patients (75%) were successfully weaned from it. Forty three patients (83%) survived. Significant differences between the initial 20 patients treated from 1978 through 1984 and the next 32 from 1985 through 1990 were duration of PN therapy (25.1 v 11.4 months; P = .04), incidence of PN associated jaundice (80% v 31%; P = .001), and survival (65% v 94%; P = .02). NEC patients had a significantly lower mean birthweight than those with other etiologies (mean, 1,367 v 2,544 g; P less than .0001) but did not differ in initial small bowel length, ICV retention rate, duration of PN treatment, incidence of successful PN weaning, or outcome. The presence of an ICV did not correlate with successful PN weaning but did affect the mean duration of PN therapy (7.2 months with ICV v 21.6 months without; P = .03).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1501010 TI - Aganglionosis in rodents. AB - The etiology of aganglionosis of the bowel remains controversial. Initial embryological studies in chicks, mice, and humans suggested the defect was in the migratory capacity of the vagal neural crest cells. This traditional theory has recently been challenged by the demonstration of a defect in the local microenvironment and the suggestion that neural crest cells migrate normally until they reach the terminal defective segment of bowel which then excludes them. To contribute to this debate we studied three rodent animal models using histological, "in vivo" (kidney capsule), and "in vitro" (tissue culture) techniques. The results suggest that there is no discernible difference between mutant and normal embryos in the early migration from the vagal neural crest to the stomach. Migration through the small bowel is normal in mutant mice, but is slowed in the rat. In both strains of mice the migration of enteric precursors into the mutant colon is slowed over an extended period of time, such that a difference between normal and mutants is evidenced well before the final aganglionic region is reached. Aganglionosis is the result either of a defect in vagal neural crest migration or in the microenvironment over an extended area of the bowel and not just in the terminal aganglionic colon. There are changes in the appearance of mutant enteric neurons in tissue culture and some alterations in the gut mesenchyme; it remains to be determined which is the primary event. PMID- 1501011 TI - Ectopic class II major histocompatibility antigens in Hirschsprung's disease and neuronal intestinal dysplasia. AB - Although the etiology of Hirschsprung's disease and neuronal intestinal dysplasia remains obscure, both have histological abnormalities involving ganglion cells and neuronal elements. Searching for a common pathway that may inhibit normal maturation of neurogenic precursors, we examined the possible role of an immune mechanism in the maldevelopment of the enteric neural network. Six patients with Hirschsprung's disease were studied by comparing biopsy specimens from diseased colon with ones taken from proximal ganglionic colon in the same patients. These were similarly compared with colonic biopsy specimens from patients studied with chronic constipation or bowel removed at the time of operation for other disorders. Biopsies were taken from four other patients with neuronal intestinal dysplasia. Each was examined by hematoxylin & eosin staining, acetylcholinesterase histochemistry, and immunohistochemistry of major histocompatibility complex (MHC) class I and class II antigens. All rectal samples from Hirschsprung's disease patients exhibited elevated acetylcholinesterase histochemistry and absent ganglia to confirm the diagnosis. These findings were correlated with marked elevation of class II MHC in the aganglionic area, whereas the proximal normal ganglionic segments showed no elevation. Rectal biopsy specimens from patients with chronic constipation exhibited no such elevation. A similar elevation of class II MHC was detected in the mucosa and submucosa of all four patients with the rare neuronal intestinal dysplasia disorder whose diagnosis was confirmed by giant ganglia in Auerbach's plexuses, aberrant Meissner's ganglia in the lamina propria mucosa, and giant neurofibrils in the mucosa and submucosa. The correlation of elevated class II MHC in these two neuronal dysfunction disorders may indicate an underlying autoimmune mechanism as is seen in thyroiditis and insulin dependent diabetes mellitus.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1501012 TI - Morbidity associated with total colon Hirschsprung's disease. AB - Increased awareness of total colon Hirschsprung's disease (TCH) has led to improvement in patient care and a decrease in the associated mortality. Morbidity has remained high and necessitates close follow-up to prevent the development of life-threatening complications. We retrospectively reviewed the records of 20 children with TCH treated at this institution since 1961. Follow-up averaged 40.4 months (range, 1 to 150). All patients were diverted with an ileostomy or jejunostomy. Eight children had a Swenson pull-through, three had a Martin procedure, and eight had a Kimura procedure. One child with multiple anomalies died after his ileostomy. There were no postoperative deaths. Complications following ileostomy and pull-through procedures included excessive fluid losses, wound infections, stoma problems, and bouts of enterocolitis. Three children had no reported complications. Seventeen complications were reported in eight children with the Kimura procedure, 10 in the three children with the Martin procedure, and 22 in the eight children with the Swenson procedure. These complications resulted in an average of 4.4 admissions per patient (range, 1 to 11) with an average length of stay of 96 days per patient (range, 10 to 598). Twelve patients required an average of 63 days of total parenteral nutrition and eight needed 328 days (range, 23 to 867) of supplemental nasogastric feedings. Ten patients required at-home rectal irrigations and seven patients required rectal dilations. Nearly half of all patients were kept on antimotility agents long term. Since 1985 we have performed the Kimura procedure for all children with TCH and have seen a decrease in morbidity.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1501013 TI - Delayed repair and preoperative ECMO does not improve survival in high-risk congenital diaphragmatic hernia. AB - It has been suggested that delayed repair with preoperative stabilization might improve survival in high-risk (symptomatic within 6 hours of birth) congenital diaphragmatic hernia (CDH). This study compares the results of immediate operation versus delayed repair using extracorporeal membrane oxygenation (ECMO) when necessary. Since we first used ECMO in 1984, 101 high-risk CDH infants have been treated. Prior to 1987, we used immediate repair and postoperative ECMO if necessary. Between 1987 and 1990 we combined delayed operation (24 to 36 hours) with preoperative ECMO as necessary. No infant in this series was excluded from ECMO therapy unless absolute contraindications existed (prematurity, intracranial hemorrhage, or other major anomalies). Fifty-five patients received immediate operation and 46 had delayed repair. The two groups were comparable populations based on gestational age, birth weight, age at onset of symptoms, Apgar scores, best postductal PO2 (BPDPO2), and frequency of antenatal diagnosis. There was no statistically significant difference in overall survival between the two groups. Differences in survival among subpopulations (BPDPO2 greater than 100 or less than 100, antenatal diagnosis, inborn v outborn) also are not significant. The requirement for ECMO was similar in both groups. Survivors in the delayed repair group were ventilated longer and on ECMO longer, but had fewer late deaths (greater than 21 days) and fewer pulmonary sequelae (O2 dependency at discharge) than infants in the immediate repair group (P less than .05).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1501014 TI - Mechanical forces contribute to neonatal lung growth: the influence of altered diaphragm function in piglets. AB - Neonatal lung growth is controlled in part by mechanical forces. Altered mechanical forces precipitated by phrenectomy or prosthetic replacement of the diaphragm result in altered thoracic volume relationships, which, in turn, change lung distending pressures and or thoracic volume. These effects might contribute to regional lung growth. We postulated a relationship between altered thoracic mechanical forces and changes in lung growth and asked if altered diaphragm function influenced regional lung growth. Piglets (28d, 7-8kg), were assigned to left transthoracic phrenectomy (P), prosthetic diaphragm replacement (PDR), or sham (S), (n = 6). After a mean 10 days, piglets were studied with tracheostomy and regional pleural pressure transducers. Integrated lung volumes (LV) were recorded with intrapleural pressure (Pip). Dynamic compliance (Cdyn) was calculated (dV/dP). After sacrifice continuous pressure volume (P/V) curves were generated. Lungs were then cut into 4 quadrants based on relationship to R/L bronchus and processed for DNA content and total protein indexes. Analysis of data were made within and between groups. Body weight and gain were similar in all. LV, Pip, Cdyn, and P/V were not significantly different in PDR and P compared with S. Pip differences between thoracic regions within each group were significant for PDR and showed LU less than RU, LL less than RL (P less than 0.05). RU and RL Pip in the PDR group were the same as S. Pip in the P group were decreased in the RU, LU, and LL but only the LL approached significance. Whole lung wet weights were decreased (P less than .05) in P compared to PDR and S.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1501015 TI - Pathophysiology of congenital diaphragmatic hernia II: the fetal lamb CDH model is surfactant deficient. AB - The high mortality for congenital diaphragmatic hernia (CDH) has been attributed to a combination of pulmonary hypoplasia and pulmonary hypertension. We hypothesize that a surfactant deficiency may in part be contributing to the pathophysiology of CDH. This study documents the functional, quantitative, and qualitative aspects of the surfactant status of the alveolar air-liquid interface and the type II pneumocyte in the fetal lamb CDH model. Ten lamb fetuses (gestational age, 80 days) had a CDH created via a left thoracotomy and then were allowed to continue in utero development until term. Three litter mates and three nonoperated time-dated fetuses served as controls. At term, pressure-volume curves were performed to measure pulmonary compliance and total lung capacity. Alveolar lavage was then performed to measure the quantitative and the qualitative aspects of pulmonary surfactant. Finally, isolation of type II pneumocytes allowed quantification of phospholipid synthesis. When compared with controls (N = 6), the CDH lambs (N = 5) had significantly smaller lungs (P = .009), decreased total lung capacity (P less than .001) and compliance (P less than .001), reduced total lavaged phospholipids (P = .006), and decreased percent phosphatidylcholine (P = .02). CDH lambs also had increased total lavaged proteins (P = .05) and higher minimum dynamic surface tension (P less than .001). A surfactant deficiency may be contributing to the pathophysiology of CDH. Surfactant replacement therapy in premature infants has been shown to improve lung compliance, decrease morbidity, and improve survival. Exogenous surfactant may also benefit infants with CDH. PMID- 1501016 TI - Participants in the Pediatric Surgical Matching Program (PSMP) PMID- 1501017 TI - Continence after posterior sagittal anorectoplasty. PMID- 1501018 TI - Risk of sudden infant death from gastroesophageal reflux. PMID- 1501019 TI - Emergency management of patients with bleeding gastric varices uncontrollable by endoscopic sclerotherapy and tamponade. PMID- 1501020 TI - Colotomy with minimum resection for advanced irreducible intussusception. PMID- 1501021 TI - Intussusception: barium or air? PMID- 1501022 TI - Transanorectal approach for the treatment of urogenital sinus: preliminary report. AB - The treatment of the urogenital sinus with normal rectum still represents a challenge. A perineal approach with or without a skin flap seems to be effective for those patients with a low implantation of the vagina. However, in patients with a high vaginal implantation, this treatment frequently fails to provide a good, functional vagina due to a narrow, strictured vaginal opening. Based on previous experience in the treatment of more than 80 patients with a persistent cloaca, a posterior sagittal transanorectal approach with a protective colostomy was performed in three patients with urogenital sinus and normal rectum. The pelvis was approached through a midsagittal posterior incision; the coccyx was split and the entire anorectal sphincteric mechanism was divided in the midline. The rectum was bivalved in the midline including both posterior and anterior rectal walls. This provided excellent exposure to the urogenital sinus. The vagina was then fully separated from the urogenital sinus (as described in cases of persistent cloacas), and then mobilized and sutured to the perineum. The rectum and sphincteric mechanism were meticulously reconstructed. A midline incision assures the preservation of anorectal innervation, and provides excellent exposure to the pelvis. Anal dilatations are not necessary to maintain a patent and supple anorectal opening because the rectum has two suture lines, one in front of the other. After the colostomy was closed, all patients had appropriate bowel control for their age; two of them are fully continent for urine and the third one still has a suprapubic cystostomy tube waiting for a repair of an additional urethral malformation. PMID- 1501023 TI - Intestinal myoelectric activity and contractile motility in dogs with a reversed jejunal segment after extensive small bowel resection. AB - To evaluate the functioning and effectiveness of a reversed jejunal segment after extensive small bowel resection, we continuously measured the postoperative bowel motility (using bipolar electrodes and/or contractile strain gage force transducers) in interdigestive and postprandial conscious dogs at 2 to 5 weeks after surgery. The fasting duodenal migrating myoelectric (or motor) complex (MMC) occurred at markedly longer intervals in dogs with a 20-cm reversed jejunal segment created after 75% to 80% extensive small bowel resection (group 3) than in dogs that received extensive resection alone (group 2) or dogs that underwent construction of a reversed jejunal segment without bowel resection (group 1). The MMC arising from the duodenum was often interrupted at the jejunum above the proximal anastomosis and did not migrate smoothly to the reversed segment or terminal ileum in group 3. In addition, brief small discordant contractions were frequent in the reversed segment and the jejunum above the proximal anastomosis in group 3. The duration of the postprandial period without duodenal MMC activity was significantly prolonged in groups 2 and 3. These results suggest that the transit time and passage of intestinal contents were delayed and that the periodical MMC was disturbed in group 3. The delay of transit time was due to prolongation of the interval between duodenal MMCs, the interruption of MMC propagation at the jejunum above the proximal anastomosis, the dominance of MMCs that followed the inherent anatomical continuity of the bowel, and discordant movements across the proximal anastomosis. Functional obstruction could be a potential problem in a 20-cm reversed jejunal segment inserted after extensive small bowel resection. PMID- 1501024 TI - The isolated bowel segment (Iowa model II): motility across the anastomosis with or without mesenteric division. AB - In previous reports, anastomosis has been shown to disrupt the myoelectric activity of the bowel. However, these studies have failed to delineate the role of the extrinsic nerves. Using an isolated bowel segment (IBS) and an amesenteric bowel segment (ABS), motility was evaluated by myoelectric recording across a bowel anastomosis. Ten rats were divided equally into the experimental group with the IBS and the control group with the ABS. In the IBS group, an 8-cm segment of jejunum was divided, reanastomosed, and coapted to the liver margin (Iowa model II). In the ABS group, an 8-cm segment of jejunum was coapted to the liver margin without disruption of bowel continuity (Iowa model II variant). Two weeks later, bipolar electrodes were implanted in the IBS and ABS, and normal jejunum in both groups. Mesenteric division (MD) was performed 4 weeks later to eliminate extrinsic innervation. Myoelectrical recordings were taken 2 weeks before and after MD. In the control group with IBS, incoordination in the propagation of the migrating motor complex (MMC) and reduction in the frequency of slow waves (FSW) were observed across the anastomosis and were unchanged by MD. In the control group with the ABS, the MMC and FSW were identical to that in the normal jejunum and were unaffected by MD. In both groups postprandial inhibition of the MMC was the same as in the normal jejunum and was unaffected by MD. This study confirms that incoordination in propagation of the MMC and reduction in FSW occur across a bowel anastomosis, and elimination of extrinsic innervation does not affect the autonomy of these changes.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1501025 TI - Fate of infants with neonatal hepatitis: pediatric surgeons' dilemma. AB - Thirty-five cases of neonatal hepatitis (20 males and 15 females) were reviewed, 3 of whom were lost during the follow-up, leaving 32 patients for review. There were 10 late deaths and 22 patients survived, 18 of whom with a normal bilirubin level and 4 with a bilirubin level of greater than 1.0 mg/dL. In the 18, jaundice disappeared between the ages of 4 and 7 months. The current lifestyles of the patients include 4 adults aged 19 to 21 who are either working or at university, while the other 18 children are all making good progress at school. Except for moderate growth retardation in 3 children, all are growing well. In all 10 patients who died, liver failure persisted until the time of death. Three died of other causes and 7 died of neonatal hepatitis itself between 4 months and 7 years of age. Four patients ran a fulminating course resulting in death between the ages of 4 and 12 months. All 7 had growth and developmental retardation. A histological examination showed that in those who died, there was significantly more periportal fibrosis, inflammation in the periportal area, and diffuse giant cell transformation. These results indicate that some infants with neonatal hepatitis have a poor prognosis and, therefore, the identification of such a condition requires a careful, long-term follow-up. PMID- 1501026 TI - Laminin and procollagen-III-peptide as a serum marker for hepatic fibrosis in congenital biliary atresia. AB - The extracellular matrix (ECM) is a complex of macromolecules that includes collagens, proteoglycans, and complex glycoproteins. In fibrotic liver tissue there is an increase in all of these matrix components, and they increase in serum in the patients with alcoholic hepatitis or liver cirrhosis. These ECM components have been used as a serum marker of hepatic fibrosis. Prolonged obstruction of bile flow results in morphologic and biochemical changes and the development of secondary biliary cirrhosis. In congenital biliary atresia (CBA) there is a close correlation between the degree of the hepatic fibrosis and bile flow after the operation. We estimated that, in CBA, ECM increased in serum, and it would reflect the degree of the hepatic fibrosis. To clarify this we examined the serum procollagen-III-peptide (P-III-P) and laminin in CBA patients. P-III-P was elevated in all preoperative patients but in two of the three postoperative patients whose jaundice disappeared P-III-P was in the normal range. In the all 3 patients whose jaundice continued, P-III-P was in normal range. Serum laminin was elevated in 12 preoperative patients with CBA, but there is no correlation between day of diagnosis and level of laminin. Mean concentration in CBA without jaundice after operation was 3.18 U/mL, 3.226 U/mL in CBA with jaundice and 3.3 U/mL in infantile hepatitis. There were no significant differences among three groups. With the elevation of serum alanine aminotransferase, aspartate aminotransferase, and total bilirubin, serum laminin level was also increased.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1501028 TI - The future role of hepatic portoenterostomy as treatment of biliary atresia. AB - According to our recent study, 38 of 93 patients (40.9%) who underwent portoenterostomy at Juntendo University Hospital between 1977 and 1986 survived for more than 5 years. In order to learn the future improvement of the prognosis of biliary atresia patients who undergo portoenterostomy, we investigated the relationship between the prognosis of biliary atresia patients and the age and the histological changes of liver at the time of surgery. Twenty-seven of 30 patients (90%) who survived for more than 5 years with no jaundice and no findings of liver cirrhosis had a mild degree of liver fibrosis (F1 or F2) and a mild degree of degeneration of intrahepatic bile ducts (B1 or B2) at the time of surgery, in spite of the difference of size of intrahepatic bile ducts at the porta hepatis. On the other hand, all 8 patients who showed severe liver fibrosis (F3) and severe degeneration of intrahepatic bile ducts (B3) did not survive for more than 5 years. Accordingly, we can expect promising prognoses in patients who undergo refined portoenterostomy procedures and receive proper postoperative treatment before they have severe histological changes of liver. The portoenterostomy will still play an important role as treatment of biliary atresia in the future. PMID- 1501027 TI - The efficacy of Kasai operation for biliary atresia: a single institutional experience. AB - To assess the efficacy of Kasai operation for biliary atresia, 60 cases during a 14-year period (1976 to 1989) at this institution were reviewed. Thirty-four (56.7%) underwent operation within 90 days of life, 11 (18.3%) between 90 and 120 days and 15 (25.0%) beyond 120 days. Fifty-six underwent hepaticoportojejunostomy and 4 underwent hepaticoportocholecystostomy. Follow-up was 1 to 14 years (mean, 7.2 years). The postoperative follow-up of these 60 patients was categorized into five groups: group A (16 patients, 26.7%) was characterized by survival greater than 3 years and without jaundice; group B (3 patients, 5.0%) was defined as survival greater than 3 years, but with jaundice; group C (11 patients, 18.3%) was defined by survival but follow-up less than 3 years, (this group was further divided into C1 [7 patients, 11.7%] if anicteric and C2 [4 patients, 6.7%] if icteric); group D (2 patients, 3.3%) was patients who underwent liver transplantation; and group E (28 patients, 46.7%) was the group of patients who died at time of review. Group A and group C1 were interpreted as success after Kasai operation; hence, the potential success rate in this series was 38.3% (23 patients). They were long-term survivers, and most of them performed normal activities appropriate for their ages. We conclude that approximately one third of patients with biliary atresia would benefit from or be cured by this operation, which should be the first attempt in the treatment of this disease entity. PMID- 1501029 TI - What is the optimal depth for core-out toward the foramen cecum in a thyroglossal duct cyst operation? AB - The high recurrence rate of thyroglossal duct cyst operations is well documented. Sistrunk's operation is widely accepted as the best procedure to prevent recurrence. Nonetheless, the optimum depth of core-out is still not well documented. We previously reported a standard running pattern of the thyroglossal duct in an anatomical reconstruction study. In more detailed pathological studies, we have tried to determine the optimal depth for core-out toward foramen cecum and the optimal width of the hyoid bone to be resected. The following items were clarified. (1) Double the horizontal distance from midline to the most distant thyroglossal duct in front of the hyoid bone was 2.4 to 9.6 mm. (2) The length of the single duct above the hyoid bone which spreads into many ductuli as it approaches the foramen cecum was about 3 to 5 mm in 2- to 6-year old children. (3) The diameter of the thyroglossal duct at the level of the cranial top of the hyoid bone was 175 to 1,400 microns. Half of the examined cases were less than 500 microns, which may have rendered direct dissection impossible. Based on these studies, we propose: (1) that a minimum of 10 mm of the hyoid bone should be resected, and for the sake of safety, more than 15 mm is preferable; and (2) that the depth of the core-out should be less than 5 mm in young children to avoid the breakdown of the branched ductuli near the foramen cecum. PMID- 1501030 TI - Peripheral congenital arteriovenous fistulae: observe, operate, or obturate? AB - In 1976, we presented our experience in the surgical management of patients with peripheral congenital arteriovenous fistulae (CAVF). This report updates our experience and specifically describes subsequent experience with intraarterial embolization therapy. Twenty-six infants and children with CAVFs have been treated at Children's Hospital of Los Angeles from 1966 to 1990. The majority of lesions were lower extremity (12), followed by upper extremity (8), shoulder girdle (3), and thorax/neck (3). Seventeen patients had lesions in multiple locations. All patients under 1 year of age had upper extremity lesions, all in the 5- to 10-year age group had lower extremity lesions, and all over 15 years of age at presentation required amputation. Twelve patients had initial embolization therapy and 12 had surgery. Seven of eight patients followed after embolization have improved. Embolization is not effective in large or ulcerated lesions. All patients with embolization alone have residual disease and three of eight have discrepancy in extremity length. Surgery has a 50% complication rate and 7 of 10 followed surgery patients have residual disease. Radiologic catheter techniques and embolization provide a valuable alternative therapy for CAVFs and should be used as the primary form of treatment in most cases. PMID- 1501031 TI - Traumatic arteriovenous fistula: a complication of amniocentesis. AB - Fetal injury is a potential complication of amniocentesis. We report the case of an infant who had an isolated arteriovenous fistula between the popliteal artery and vein that resulted from amniocentesis. Unlike the usual congenital arteriovenous communications that are multiple and difficult to treat, this case was completely cured by division of the fistula and vascular repair. This case emphasizes that newborns and infants who have had invasive prenatal interventions such as amniocentesis should be identified and the possibility of fetal injury be considered when evaluating their clinical signs and symptoms. PMID- 1501032 TI - Bannayan-Zonana syndrome associated with lipomas, hemangiomas, and lymphangiomas. AB - Bannayan-Zonana syndrome is a rare disorder characterized by macrocephaly and multiple soft tissue and visceral hamartomas. This report presents a sporadic patient with macrocephaly, lipomas, hemangiomas, and lymphangiomas who died of cardiac and respiratory failure due to progressive cervicomediastinal arteriovenous fistulous hemangiomas at the age of 9 years. PMID- 1501033 TI - Communicating bronchopulmonary foregut malformations: classification and embryogenesis. AB - Communicating bronchopulmonary foregut malformations (CBPFMs) are characterized by a fistula between an isolated portion of respiratory tissue (ie, a lung, a lung lobe, or a segment) and esophagus or stomach. We combine our 30-year (1959 to 1989) experience of 6 cases with 51 reported patients to propose a CBPFM classification supported by a proposed embryogenesis theory. Group I (16%): anomaly is associated with esophageal atresia and tracheoesophageal fistula. Group II (33%): one lung originates from the lower esophagus. Group III (46%): an isolated anatomic lung lobe or segment communicates with the esophagus or stomach. Group IV (5%): A portion of the normal bronchial system communicates with the esophagus. The portion of the lung served by the communicating bronchus receives systemic blood supply. The right and left lung sacs curve dorsally to embrace the lower esophagus during normal lung development. At this stage a part of the lung bud joins the esophagus. This segment then breaks away from the main pulmonary anlage to form a CBPFM. CBPFMs should be considered in the workup of infants with respiratory distress and/or recurrent pneumonias. Patients with suspected pulmonary sequestration should undergo contrast studies to exclude a gastrointestinal communication. PMID- 1501034 TI - Mucormycosis of the neonatal gut: a "new" disease or a variant of necrotizing enterocolitis? AB - Mucormycosis is an opportunistic infection that has been mainly described in adults with preexisting disease affecting immune status, eg, diabetes, leukemia, lymphoma, and renal failure on peritoneal dialysis. Few cases have been described in neonates. The presentation of mucormycosis as a cause of neonatal necrotizing enterocolitis is an unusual phenomenon. Three fatal cases of mucormycosis of the gut in premature infants in the period 1990 to 1991 are described. It is not clear whether this should be considered a separate disease or a variant of necrotizing enterocolitis. All three patients died soon after laparotomy from septic shock and the histological diagnosis of mucormycosis was made too late for effective chemotherapy. PMID- 1501035 TI - Treatment for necrotizing enterocolitis perforation in the extremely premature infant (weighing less than 1,000 g). AB - The frequency of necrotizing enterocolitis (NEC) in the extremely premature infant (less than 1,000 g) is still high and it is very difficult for infants weighing less than 1,000 g with NEC perforation to survive. In our institutes, the management protocol for NEC perforation in infants weighing less than 1,000 g includes peritoneal drainage under local anesthesia, administration of coagulating factor XIII, and the usual treatment for septic shock. During the past 3 years, four infants weighing less than 1,000 g with NEC perforation have survived using this protocol without laparotomy. This management protocol is the treatment of choice in infants in very poor condition or infants weighing less than 1,000 g with NEC perforation. PMID- 1501036 TI - Perforated pseudomembranous colitis in the breast-fed infant. AB - Pseudomembranous colitis (PMC) is uncommon in the infant and complications requiring surgical intervention are rare. All prior cases have involved the direct administration of antibiotics to the child. A 2-month-old girl required bowel resection for perforation of a thickened and inflamed left colon. Findings were consistent with PMC and the stool was Clostridium difficile toxin positive. The patient was treated with vancomycin and did well. The patient's mother later admitted to self-administration of ciprofloxacin while breast-feeding her infant. Oral doses of this drug are concentrated in breast milk at levels higher than serum. Antibiotics derived from breast milk can cause complicated PMC in the infant. A directed history can establish an early diagnosis and help distinguish PMC from other more common infantile enterocolitides. PMID- 1501037 TI - Microperforation of a duodenal diaphragm as a cause of paradoxical gas in congenital duodenal obstruction. AB - An infant who presented with signs of duodenal atresia had proximal duodenal obstruction by upper gastrointestinal barium study, but had a small amount of air in the distal bowel. Exploration showed an annular pancreas and microperforation of a duodenal diaphragm. Prior to concluding that pancreaticobiliary duct anomalies are the path of air into the distal bowel in patients with duodenal atresia, microperforation of a duodenal diaphragm must be excluded. PMID- 1501038 TI - Continuous gastric pH monitoring in children: the effect of gastric emptying on the measurement of gastric acid secretion. AB - Continuous gastric pH monitoring offers the opportunity to evaluate gastric acid secretion in humans without the need for collection of gastric aspirates. However, gastric emptying may be an important variable for the accurate measurement of gastric acid secretion using continuous gastric pH monitoring. We conducted an in vitro study (phase I) to evaluate the effect of gastric emptying on gastric pH. The in vitro study used a laboratory model in which continuous pH monitoring of a standard formula (Nutramigen, 100 mL) in a reservoir was performed while varying both the reservoir emptying rate (10% to 80%) over 1 hour and the amount of added acid (2 to 15 mEq/h: in vivo equivalent of 6 to 45 mEq/m2 BSA/h). An in vivo study (phase II) was then performed in 28 infants less than 6 months of age who had gastroesophageal reflux (GER) documented by 18- to 24-hour esophageal pH monitoring. At the end of esophageal pH monitoring, the pH electrode was advanced into the stomach for measurement of gastric pH continuously for 2 hours after a feeding of Nutramigen formula (300 mL/m2 BSA). Each patient also had a radionuclide gastric emptying study performed with the same volume of Nutramigen formula. In the in vitro model, the reservoir pH (% time pH less than 4) was proportional to the reservoir emptying rate only when acid was added at less than 15 mEq/h (less than 45 mEq/m2 BSA/h). Reservoir pH was independent of reservoir emptying rate when acid was added at 15 mEq/h (45 mEq/m2 BSA/h).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1501039 TI - ECMO and the management of congenital diaphragmatic hernia with large diaphragmatic defects requiring a prosthetic patch. AB - From 1977 to 1991, 136 neonates have had corrective surgery for diaphragmatic hernia at Children's Hospital of Los Angeles. A retrospective study was performed to determine how many of the 136 neonates had defects large enough to require the use of a prosthetic patch to repair the defect. Twelve were found. All 12 were symptomatic at birth for respiratory distress. Mean arterial blood gas values at birth were pH 6.95, PCO2 94.8, and PO2 47.2. The mean oxygen index (n = 10) was 61.8. Six of these patients were repaired without extracorporeal membrane oxygenation (ECMO) support while the other six received ECMO bypass perioperatively. All six of the patients who did not receive ECMO support died despite successful diaphragmatic repair. Five of six patients who received ECMO perioperatively survived (83%). These surviving infants are now between 1 month and 4 years of age. In the survivors, four of five required subsequent repair and patch enlargement for a recurrent diaphragmatic hernia. Gastroesophageal reflux, requiring a Nissen fundoplication in two infants, complicated the course of three survivors. Four survivors were discharged with supplemental oxygen therapy lasting less than 13 months. Patch disruption is predicted to occur at approximately 18 months of age in all patients, especially if little or no muscle was available at primary repair for prosthetic attachment. These children should be followed closely for feeding or respiratory symptoms. Diagnosis of patch disruption can be made by chest x-rays and confirmed by contrast studies. Patch expansion by laparotomy and careful search for additional musculature for patch attachment is recommended when reherniation occurs. PMID- 1501040 TI - Testicular feminization: the androgen insensitivity syndrome. AB - Testicular feminization (TF) is a syndrome due to androgen insensitivity. It occurs in a complete (CTF) and an incomplete (ITF) form. We have treated 21 patients with TF over the last 24 years. Eight patients presented because of ambiguous genitalia, seven presented as "females" with inguinal hernia and testes were found at surgery, five were diagnosed by karyotyping performed for a family history of TF, and one presented with an incarcerated hernia and primary amenorrhea. Two patients had prior surgery for inguinal hernia but the diagnosis was not recognized. All patients had a 46,XY karyotype. Patients with CTF were phenotypically female while those with ITF had a variable appearance of the external genitalia depending on the degree of androgen insensitivity. Seventeen patients underwent gonadectomy and one patient planned for delayed gonadectomy was lost to follow-up. Seventeen patients had been raised as females since birth. One patient with ambiguous genitalia, who was initially raised as a male, was reassigned female gender at 1 year of age when the diagnosis of ITF was made. Three patients were raised as males even after the diagnosis of ITF was made. Patients raised as males underwent multiple genital reconstructive procedures with poor results. In view of the poor anatomic and functional results of genital reconstructive surgery and the consequent psychological problems, patients with TF should be raised as female. Careful evaluation of infants with ambiguous genitalia and documentation of absent fallopian tubes in "females" presenting with inguinal hernia will lead to early diagnosis of TF, correct sex assignment, and early gonadectomy. PMID- 1501041 TI - A case of ectopic opening of vasa deferentia into mullerian duct cyst. AB - We report very rare case in which the vasa deferentia entered a large Mullerian duct cyst in a 4-month-old infant. The presenting findings were lower abdominal mass and the complaint of urinary retention. A computed tomography scan of the pelvis showed a monolocular cystic mass between the bladder and the rectum. Surgical removal of the cyst was done because the mass increased in size and both hydronephroses and hydroureters were getting worse despite the use of antibiotics. The patient has no urological difficulty after the operation. This case was characterized as follows: the cyst was located on the midline, the vasa entered the cyst directly, the size of the cyst was large, and it was not associated with other malformations of the genitourinary system. PMID- 1501042 TI - Right-sided diaphragmatic hernia following group B streptococcal pneumonia and sepsis. AB - A case of right-sided diaphragmatic hernia following group B streptococcal pneumonia and sepsis is reported herein. The clinical course was characteristic. The position of the right hemidiaphragm was initially normal. After an antecedent group B streptococcal infection, an abnormal shadow indicating either pneumonia or a pleural effusion on the chest x-ray was recognized and an elevation of the bowel and liver into the right hemithorax gradually appeared. Repair of the hernia was indicated and the postoperative result was excellent. The relationship between a delayed-onset diaphragmatic hernia and a group B streptococcal infection is still unknown. Increased intrathoracic pressure caused by mechanical ventilation coupled with an abnormal lung compliance due to inflammation may have resulted in the delayed herniation. Among various methods for diagnosis applied, chest x-ray and ultrasonography were noninvasive and useful. PMID- 1501043 TI - Conservative treatment of caustic esophageal strictures in children. AB - The most common cause of esophageal stricture in children is the accidental ingestion of strong corrosive agents. During a 13-year period between 1976 and 1989, 202 patients were diagnosed as having caustic esophageal strictures at the Hacettepe University Children's Hospital Department of Pediatric Surgery. A retrospective clinical study was performed to find out the place and predictors of a successful outcome for conservative treatment in children who have caustic esophageal strictures. Two hundred two children, of whom 145 were male (71.7%) and 57 female (28.3%) with 168 (83.2%) being younger than 6 years of age, were evaluated retrospectively. Whereas only 49.3% of patients could be treated within a 12-month period, 50.7% needed more than 1 year, 32.9% needed more than 2 years, 26.7% needed more than 3 years, and 15.4% needed more than 4 years of periodic dilations in order to become swallowers through native esophaguses. The success of conservative treatment has been higher in patients younger than 8 years of age, and in strictures due to caustics other than lye involving upper third portion and less than five cm of an esophageal segment. Most caustic esophageal strictures could have been treated by conservative measures in children. PMID- 1501044 TI - Colonic replacement for the treatment of caustic esophageal strictures in children. AB - Caustic esophageal stricture is one of the most common indications for esophageal replacement in children. During a 13-year period between 1976 and 1989, colonic replacement was performed in 50 patients for the treatment of caustic esophageal strictures at the Department of Pediatric Surgery of Hacettepe University Children's Hospital. A retrospective clinical study was undertaken to discuss the indications and results of colonic replacement. The 50 children, 34 of whom were male (68%) and 16 of whom were female (32%) with 27 patients (54%) under 6 years of age, were evaluated retrospectively. Indications for operation included 21 (42%) who could not swallow saliva and had total or nearly total obliteration of lumen involving more than 3 cm of an esophageal segment at admittance, and 16 (32%) who had difficulty in swallowing within a 1-month period following the last dilation after completion of a 1-year dilation program. A further 13 (26%) had bleeding and difficulties during dilations, after experiencing an esophageal perforation. The right colon was used in 48 and the left in the remaining 2 patients. Patients were followed for at least 1 year following replacement. Growth was excellent in all but one patient who had redundant colon and showed growth retardation. There was one postoperative late death because of massive bleeding from ulceration of the transplanted colon. The other 49 patients were available for accurate follow-up. The results were good, 46 (92%) were able to eat everything, while occasional dysphagia in 3 (6%) required dilation after operation. Colon conduit provides an excellent substitute for esophagus in pediatric patients.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1501045 TI - Abbreviated esophageal pH monitoring as an indication for fundoplication in children. AB - Intraesophageal pH recordings from 40 patients with abnormal studies who underwent fundoplication during a 1-year period were evaluated. Scores were recalculated for the first 12, 16, and 20 hours, respectively. Five of the recordings were for less than 24 hours, but were grossly abnormal and mathematically could not have normalized at 24 hours. The percentage of studies which were normal at 12, 16, and 20 hours were 20%, 15%, and 0%, respectively. One fifth of the patients would have been denied a fundoplication based on 12 hour results. In addition, 75 consecutive pH recordings were evaluated prospectively. Total scores were determined for the first 12, 16, and 20 hours with accuracies of 85%, 93%, and 92%, respectively. The sensitivity of 12-hour monitoring was only 78%. All abbreviated studies had a low rate of false positives; however, any false positives may be significant when used to determine the need for an operation. Abbreviated studies were associated with high false negative rates (up to 52% for the 12-hour studies) for the calculated mean duration of sleep reflux, a parameter that has been found to be useful in identifying patients with respiratory symptoms secondary to gastroesophageal reflux. The use of abbreviated pH monitoring is discouraged. PMID- 1501046 TI - Stomach position as an in utero predictor of neonatal outcome in left-sided diaphragmatic hernia. AB - An 8-year review of neonates with left-sided congenital diaphragmatic hernia who presented in severe respiratory distress at birth was retrospectively reviewed looking at stomach position, thoracic or abdominal, as a predictor of survivability. Survival was 93% with the stomach below the diaphragm compared with 29% when the stomach was thoracic in location. Stomach position may be an important early in utero predictor of high mortality in neonates with left-sided congenital diaphragmatic hernias. PMID- 1501047 TI - Surgical aspects of chronic peritoneal dialysis in the neonate and infant under 1 year of age. AB - Since 1982 eight patients under 1 year of age with end-stage renal failure have been treated by chronic peritoneal dialysis (CPD) following insertion of an abdominal Tenckhoff catheter. We routinely perform a partial omentectomy now, and in males undertake bilateral exploration of the groins at the time of catheter insertion, with herniotomy or ligation of the patent processus vaginalis as required. Up to January 1990, 19 straight double-cuff catheters had been inserted with a total follow-up of 244.5 patient months. The median age at the initial catheter insertion was 14.6 weeks (range, 2 days to 11 months) and the median weight was 3.89 kg (range, 2.2 to 5.5). Peritonitis was the most common complication, with 46 episodes, representing one episode of peritonitis per 5.3 patient months on dialysis. The frequency of peritonitis has decreased in the last 6 months since all patients have been dialysed by two caregivers. The present rate of peritonitis is 1 episode per 10 patient months on dialysis. One patient has died of septicemia secondary to associated congenital abnormalities, one patient has regained renal function, and two patients have been transplanted, one successfully. Five patients are currently dialysing via their abdominal Tenckhoff catheters and awaiting transplantation. We conclude that neonates and infants under 1 year of age can be treated satisfactorily by CPD to enable successful preparation for transplantation later in childhood. PMID- 1501048 TI - Seven children are described with incapacitating fecal incontinence. PMID- 1501049 TI - Midgut malrotation associated with hypertrophic pyloric stenosis had concomitant congenital short bowel. PMID- 1501050 TI - Neonatal colorectal spindle cell sarcoma. PMID- 1501051 TI - Complete tumor resection are warranted in poor-risk neuroblastoma. PMID- 1501052 TI - The effect of antenatal intravenous immunoglobulin on ascending intrauterine infection after preterm premature rupture of the membranes: a pilot study. AB - Ascending infection is a serious threat in pregnancies complicated by preterm premature rupture of the membranes (PROM). In a controlled randomized prospective pilot study (n = 18) we have evaluated the effect of intravenous IgM enriched immunoglobulin given to the mothers 24-48 hours after preterm PROM in reducing ascending infection. Using a validated infection score from laboratory and clinical data at birth, we found a significant reduction of probable infection in the neonates of the treatment group compared to the control group (p = 0.0022). Histopathological investigation of the placentas, membranes and umbilical cords revealed significantly lower stages and grades of chorioamnionitis in the treatment group (p = 0.036). From these preliminary results we conclude, that intravenous broad spectrum immunoglobulin given antenatally to patients with preterm PROM may reduce ascending infection. However, studies with a much larger cohort of patients are necessary to confirm these preliminary results and to detect potential clinical benefits from this treatment mode. PMID- 1501053 TI - Triplets are not so rare any more. AB - Triplet gestations present a considerable management challenge due to a high rate of antenatal, intrapartum and neonatal complications. The introduction of ovulation inducing agents resulted in a marked increase of these pregnancies. Consequently, triplet conceptions are not considered a rare phenomenon and have become almost routine high risk pregnancies. In our department the triplet gestation frequency increased 2-4 times in a 10 year period from a rate of 0.07 0.14% during 1978-84 to 0.28% of all deliveries in 1987. This high incidence of triplet deliveries results in a threefold increase in the frequency of triplet neonates and their associated complications. It is reasonable to assume that the wide application of various assisted reproductive techniques will result in continuous increase in the incidence of triplets which will in turn require coordinated management of a high risk pregnancy unit, delivery room and neonatal intensive care unit. PMID- 1501054 TI - Abnormal platelet lipid membrane composition in pregnancy induced hypertension. AB - The cholesterol:phospholipid ratio (C/PL) was measured in platelet plasma membrane in patients with pregnancy-induced hypertension [with proteinuria (PE), and without proteinuria (PIH)] and in matched normotensive gestational controls (NT). The C/PL was raised in the platelet membrane from PE (1.52 +/- 0.50, 95% CI 1.13 to 1.90) and PIH (1.38 +/- 0.34, 95% CI 1.08 to 1.67) compared with that from NT controls (0.88 +/- 0.13, 95% CI 0.80 to 0.95) (p less than 0.01, ANOVA test). No correlation was found when C/PL was regressed against total serum cholesterol levels. The abnormality of lipid composition of the platelet plasma membrane could account for some of the changes in platelet function that have been described in PIH. PMID- 1501055 TI - Immunological studies in placentas with villitis of unknown etiology: complement components and immunoglobulins in chorionic villi. AB - Villitis of unknown etiology (VUE) is a common placental lesion and complement fixing immune complexes is one of the mechanisms proposed for its development. We examined 16 placentas with VUE and 16 without VUE by immunofluorescence in order to compare the distribution and amount of C1q, C3d, IgG and IgM in the chorionic villi between the two groups. We found both in cases with and without VUE a distribution of the complement components and immunoglobulins similar to that described in normal placentas. The amount of deposit was also not significantly different in the two groups. Only the inflamed villi showed an abnormal distribution of C1q which was present diffusely in the stroma of these villi. PMID- 1501056 TI - Conjoined twins associated with a normal singleton: very early diagnosis and successful selective termination. AB - Conjoined twins were diagnosed at 10 weeks of gestation in a triplet pregnancy obtained by means of in vitro fertilization. Vaginal scan evidenced craniopagus twins associated with a singleton. Considering the poor and unpredictable prognosis, selective terminations of twins was successfully performed. PMID- 1501057 TI - Doppler flow measurements and histomorphology of the placental bed in uteroplacental insufficiency. AB - For the first time histomorphological findings of the uteroplacental vessels were correlated with Doppler flow parameters of this vascular area in a combined study. The study group consisted of 58 women with a pregnancy-induced hypertension or an otherwise presumed uteroplacental perfusion impairment delivered by cesarean section. The control group included 50 healthy pregnancies, delivered by cesarean section due to presentation anomalies or failure to proceed. After removal of the placenta a placental bed biopsy containing the uteroplacental vessels of the decidual and inner myometrial layer was taken. The occurrence of accepted histological signs of low uteroplacental perfusion was compared to Doppler flow velocity wave forms in uteroplacental arteries. The accuracy of doppler-sonographic findings of uteroplacental circulatory impairment confirmed by the histomorphological results was high, even in cases not complicated by hypertension. The good accordance of Doppler flow parameters with morphological findings offers new perspectives for differentiated insights in pregnancy courses with and without signs of uteroplacental insufficiency. PMID- 1501058 TI - Early sonographic diagnosis of fetal cystic hygroma colli. AB - Fetal cystic hygroma colli (FCHC) is a congenital malformation of the lymphatic system which develops as a result of failure of the communication between the jugular lymphatic canal and the internal jugular vein. The diagnosis is usually made by ultrasound in the second trimester of pregnancy by the demonstration of a multiseptate, thin-walled cystic mass appearing posterolaterally in position to the fetal head and neck region. In this report we present two cases of FCHC diagnosed by transabdominal ultrasound in the first trimester of pregnancy. In one case, chorionic villus sampling revealed a 45,X karyotype, the fetus became progressively hydropic and died at 15 1/2 weeks. In the other, the spontaneous resolution of a nonseptated FCHC in a fetus with normal karyotype was documented, resulting in the delivery of a healthy infant a term. Fetal karyotyping, a careful search for other anomalies that may affect fetal survival, and a close sonographic follow-up in cases of FCHC are advocated for an accurate diagnosis and genetic counselling. PMID- 1501059 TI - Seasonal incidence of eclampsia and its relationship to meteorological data in Mozambique. AB - Gestational hypertension is common in Mozambique. In a prospective study lasting 12 months every case of eclampsia in Maputo city was registered. The monthly ratio of eclampsia cases to births was calculated. With the purpose to test the hypothesis of a correlation between meteorological data and eclampsia incidence, monthly averages of temperature, humidity and atmospheric pressure were tabulated. Temperature (p less than 0.005) and atmospheric pressure (p less than 0.001) were significantly associated with the eclampsia/birth ratio. Humidity showed no significant association. We conclude that there is a statistical association between eclampsia incidence and air temperature and atmospheric pressure, respectively. PMID- 1501060 TI - Cordocentesis versus amniocentesis for rapid fetal karyotyping in cases of late referral of women. AB - Eighteen women were referred for fetal karyotyping because of advanced maternal age (over 38 years) later than 23 weeks' gestation. In order to obtain more rapid karyotypes, cordocentesis rather than amniocentesis was performed. All procedures were successful, leading to the obtention of normal karyotypes in all cases. No fetal incidents occurred and results were obtained more rapidly than by amniocentesis. We suggest the use of cordocentesis rather than amniocentesis in cases of late referral of women. PMID- 1501061 TI - Noninvasive fetal ECG mode fetal heart rate monitoring by adaptive digital filtering. AB - Beat-to-beat variability (BTBV) of the fetal heart rate (FHR) is considered an indication of the neural integrity and is an important prognostic indicator of fetal well-being. We report the initial evaluation of a recently developed abdominal fetal ECG (AFECG) mode of FHR monitoring using Adaptive Digital Filtering (ADF) to accurately obtain BTBV noninvasively. Five women in labor at term were monitored with the direct fetal scalp electrode (FSE) and simultaneously with the AFECG using ADF. A computer analysis of 3298 seconds (55 minutes) of data provided a one-to-one comparison of the R-R intervals. One analysis of the direct FSE data with a second simultaneous analysis from the same electrode, to serve as control, was compared with the noninvasive AFECG data. The study group has a standard deviation of only 1.50 bpm compared to 0.79 bpm for the control group. The AFECG method agrees with the direct FSE method within 1 bpm for 92.6% of the reported R-R intervals and within 2 bpm for 98.9% of the reported intervals. This new noninvasive AFECG technique with ADF provides a continuous record of instantaneous FHR and BTBV that may be relied upon to provide an accurate continuous clinical record. The reliability of the technique has yet to be determined over a wide range of subjects. PMID- 1501062 TI - Variance components in comparative bioavailability studies. AB - Variance components in comparative bioavailability studies are examined. Assay measurement error is shown to be negligible relative to other variance components, and hence, repeat assay does not appreciably increase study precision and is unnecessary. More important is the finding that repeat administration of each formulation to each subject may substantially decrease the variance of the formulation difference and may allow the use of fewer subjects in a study. The benefit of repeat administration depends on the relative sizes of the within subject variance component and the subject-formulation interaction component. In addition, repeat administration allows separate estimation of the within-subject component and the subject-formulation component. The former component is important for assessing bioequivalence, and the latter component, for assessing interchangeability of formulations. PMID- 1501063 TI - Modeling of the kinetics of drug release from a binary system. AB - A model of a controlled-release drug delivery system was proposed and tested by mathematical simulation. The model consisted of a cylindrical drug reservoir coated with a permeable and erodible material. The release rate is relatively constant because, while the drug concentration is diminishing, the barrier is eroding. These factors may be balanced initially, but ultimately the release rate increases or decreases markedly depending on the permeability. Two kinds of permeability-dependent behaviors were observed: (1) for high-permeability coatings, the release rate is high and constant and then decreases as the drug is exhausted; and (2) for low-permeability coatings, the release rate is low and constant and then increases as the barrier becomes thin. The proposed design combines two cylinders whose coatings have different permeabilities and exhibit complementary release behavior. Complete release occurs before total erosion of either coating. Optimization of the design and the design parameters leads to a constant release rate (within 6%) until all of the drug is released from the device. PMID- 1501064 TI - Evaluation of the mass balance assumption with respect to the two-resistance model of intestinal absorption by using in situ single-pass intestinal perfusion of theophylline in rats. AB - Methods of analyzing drug absorption data from rat intestinal-perfusion experiments are discussed in terms of mass-transfer resistances, or reciprocal permeabilities, and mass balances. Typically, a two-resistance model is used to determine the dimensionless effective permeability (P*eff) by measuring the disappearance of drug from the perfusing solution. Unstated assumptions in two resistance models are (1) the portal blood is under sink conditions and (2) complete transfer of drug occurs from the intestinal perfusate to the portal vein. The assumption of sink conditions is generally acceptable, because the drug concentration in portal blood is approximately two orders of magnitude less than in the perfusate. Single-pass intestinal-perfusion experiments were performed on rats with theophylline as a model compound. The drug mass leaving the intestinal perfusate was substantially less than the drug mass appearing in the portal plasma; that is, the assumption of complete transfer did not hold for theophylline in this experimental system. These data indicate that models based on the two-resistance theory can lead to overestimation of P*eff by the ratio of the drug mass leaving the perfusate to the drug mass appearing in the plasma. For compounds for which the assumption of complete transfer does not hold, a more accurate estimate of P*eff may be determined by dividing the value derived from perfusate data by the mass balance ratio (i.e., the drug mass leaving the perfusate divided by the drug mass appearing in the plasma). PMID- 1501065 TI - Synthesis and receptor affinities of new 3-quinuclidinyl alpha-heteroaryl-alpha aryl-alpha-hydroxyacetates. AB - Five analogues of 3-quinuclidinyl benzilate were prepared in which one phenyl ring was substituted by a heterocycle; a bromine was included on either the remaining phenyl or the heterocycle to provide information relating to the affinity of potential radiohalogenated derivatives. Their affinities for the muscarinic cholinergic receptor were determined. Replacing a phenyl ring with either the 2- or 3-furyl moiety or the 2- or 3-thienyl moiety did not significantly alter the affinity to the muscarinic receptor compared with 3 quinuclidinyl 4-bromobenzilate. PMID- 1501066 TI - Enhancement of propranolol hydrochloride and diazepam skin absorption in vitro. II: Drug, vehicle, and enhancer penetration kinetics. AB - The fluxes of representative hydrophilic (propranolol hydrochloride) and lipophilic (diazepam or indomethacin) drugs, administered as ethanolic solutions containing putative penetration enhancers (n-nonane, 1-nonanol, and 1-decanol), were measured across hairless mouse skin in vitro. Propranolol transport was augmented significantly by the presence of 4% (v/v) alkane or alkanol in the vehicle; diazepam and indomethacin, on the other hand, were enhanced only by n nonane. Experiments with saturated solutions of the drugs as the donor phase revealed that the actions of the enhancers were taking place in the skin and were not a result of an alteration of solute thermodynamic activity in the vehicle. In separate runs, the impact of n-nonane and 1-nonanol on the percutaneous penetration of ethanol was determined. Temporal effects identical to those on the flux of propranolol were observed. A further measurement revealed that the penetration of 1-decanol, when administered as a 4% (v/v) solution in ethanol, followed a profile similar to that of the solvent (which, in turn, was comparable with that of the independently assessed propranolol hydrochloride). Thus, considerable linkage exists between the transport of a hydrophilic drug and the major vehicle component in the presence of n-nonane and 1-nonanol. The lipophilic drugs, conversely, were promoted only by n-nonane and only after most of the ethanol had been absorbed. The results show that an apparent synergy of transport between a putative enhancer and a cosolvent may not always lead to augmented drug flux. Study of the transport of all key formulation components is recommended, therefore, to optimize vehicles for transdermal drug delivery. PMID- 1501067 TI - Molecular connectivity model for determination of isoelectric point of amino acids. AB - A molecular connectivity model for the calculation of the isoelectric point of amino acids is presented. The model requires calculation of the molecular connectivity values of only the functional fragments of the amino acids. Multiple linear regression with two variables shows the best fit between experimental and calculated data. PMID- 1501068 TI - Effect of gastrointestinal maturation on absorption of beta-lactam antibiotics. AB - Gastrointestinal absorption of cefazolin, which is poorly absorbed in adults, and of cephradine, which is well absorbed in adults, was studied in rats during their development. Significantly higher concentrations of cefazolin in plasma after oral administration were observed in 1- and 2-week-old rats compared with 3-week old and adult rats. A marked difference in the absorption of cefazolin by 2- and 3-week-old rats (at weaning period) was observed. No such marked difference in the absorption of cephradine by rats of various age groups was found. With cefazolin, a similar pattern of developmental change in jejunal uptake was observed. Cortisone, which causes early maturation of the intestinal membrane, was given as a preweaning injection to 2-week-old rats. This treatment decreased concentrations of cefazolin in plasma and jejunal uptake of cefazolin. Thus, the absorption of cefazolin in 1- and 2-week-old rats seems to depend on the permeability of the immature intestinal membrane before weaning. Cephradine absorption from the intestine of 1-week-old rats became saturated and inhibited by carnosine and glycylglycine when studied by the in situ loop method. Cefazolin absorption was proportional to luminally administered doses and was not affected by carnosine and glycylglycine. A nonsaturable process for cefazolin and a saturable process for cephradine were also observed in an in vitro uptake experiment. PMID- 1501069 TI - Stability of diltiazem and its metabolites in human blood samples. AB - The stability of diltiazem and its metabolites in blood samples from patients under chronic diltiazem therapy was investigated. When whole blood was kept for 1 h at room temperature between sampling and centrifugation, the concentration of N demethyldiltiazem (MA) decreased significantly, with an average loss of 24%. Under the same conditions, an average loss of 14% of diltiazem occurred, whereas the concentrations of the metabolites deacetyldiltiazem and N demethyldeacetyldiltiazem did not change significantly. No significant decrease in MA and diltiazem concentrations was observed when whole blood was stored for 1 h in an ice bath. In spiked plasma samples kept at room temperature, only MA was unstable, with an average loss of 13% after 4 h. The present study shows the importance of observing rigorous conditions for the transport and treatment of blood samples. To achieve accurate determination of diltiazem and related compounds, the blood must be centrifuged immediately after collection or kept on ice for up to 1 h. The plasma samples must be immediately frozen at -80 degrees C and can be stored for up to 5 weeks before analysis. Using these rigorous conditions, we observed that MA is the main metabolite of diltiazem in plasma from patients under chronic oral diltiazem therapy. PMID- 1501070 TI - Disposition of 8-methyl-8-azabicyclo[3,2,1]octan-3-yl 3,5-dichlorobenzoate, a potent 5-hydroxytryptamine antagonist, and two metabolites in dogs and monkeys. AB - The disposition of 8-methyl-8-azabicyclo[3,2,1]octan-3-yl 3,5-dichlorobenzoate (MDL 72,222; 1), a potent 5-hydroxytryptamine antagonist, and its N-demethylated and N-oxide metabolites was studied in dogs and monkeys. After single, intravenous doses of 1 at 5 mg/kg, the mean terminal half-lives of 1 in plasma were 2.6 h in the dog and 3.8 h in the monkey. The mean half-life of the N demethylated metabolite in dogs (approximately 20 h) was very similar to that in monkeys. However, the mean half-life of the N-oxide metabolite in dogs (10.8 h) was different from that in monkeys (3.9 h). The steady-state volume of distribution of 1 was 16 L/kg in dogs and 8.9 L/kg in monkeys. Examination of the mean residence times revealed that 1, in both species, and the N-oxide metabolite, in dogs, distributed to the peripheral tissue, whereas the distribution of the N-demethylated metabolite in both species and the N-oxide metabolite in monkeys was limited mainly to the systemic circulation. Compound 1 was metabolized extensively in both species. In dogs, 0.7, 2.5 and 40.6% of the administered dose were excreted in 0-120-h urine samples as 1 and its N demethylated and N-oxide metabolites, respectively. In monkeys, however, the corresponding percentages were 0.8, 0.7, and 1.8%. Most of the administered dose in monkeys was excreted in urine as 3,5-dichlorobenzoic acid and its glycine conjugate. PMID- 1501071 TI - Absorption of acetylsalicylic acid from the rat nasal cavity. AB - The fate of salicylate in the plasma of rats was followed after nasal, intravenous, and oral administration of 2.0-mg doses of aspirin. Aspirin was well absorbed following nasal administration of a neutralized, nonirritating solution containing triethanolamine. The rate of absorption was slower than that of other nasally administered drugs, such as propranolol or progesterone. The bioavailability of aspirin following nasal administration was 100%, whereas the oral bioavailability was only 58.8% at the dose studied. PMID- 1501072 TI - Separation and quantitation of polyethylene glycols 400 and 3350 from human urine by high-performance liquid chromatography. AB - Polyethylene glycol 3350 (PEG 3350) is useful as an orally administered probe to measure in vivo intestinal permeability to macromolecules. Previous methods to detect polyethylene glycol (PEG) excreted in the urine have been hampered by inherent inaccuracies associated with liquid-liquid extraction and turbidimetric analysis. For accurate quantitation by previous methods, radioactive labels were required. This paper describes a method to separate and quantitate PEG 3350 and PEG 400 in human urine that is independent of radioactive labels and is accurate in clinical practice. The method uses sized regenerated cellulose membranes and mixed ion-exchange resin for sample preparation and high-performance liquid chromatography with refractive index detection for analysis. The 24-h excretion for normal individuals after an oral dose of 40 g of PEG 3350 and 5 g of PEG 400 was 0.12 +/- 0.04% of the original dose of PEG 3350 and 26.3 +/- 5.1% of the original dose of PEG 400. PMID- 1501073 TI - Crystal structures of a new oral iron chelator, 1,2-dimethyl-3-hydroxy-4 pyridone, and its solvates with acetic acid and formic acid. AB - The crystal structures of a new oral iron chelator, 1,2-dimethyl-3-hydroxy-4 pyridone (DMHP), and of its 1:1 solvates with formic acid (DMHP,F) and acetic acid (DMHP,A) were determined by single-crystal X-ray diffraction. The data were collected at temperatures of 23 +/- 1 degrees C for DMHP, -64 +/- 1 degrees C for DMHP,F, and -120 +/- 1 degrees C for DMHP,A. The iron chelator DMHP is orthorhombic [Pbca, a = 7.290(5) A, b = 13.046(4) A, c = 13.748(6) A, Z = 8]. The DMHP molecules form centric dimers, each in a 10-membered ring in which the OH group of one molecule is hydrogen-bonded to the CO oxygen of the other [O-H...O; 0.91(4) A, 153(3)degrees, 1.85(4) A]. In each DMHP molecule, the OH group and CO oxygen are insignificantly intramolecularly hydrogen-bonded [O-H...O; 0.91(4) A, 107(3)degrees, 2.33(4) A]. DMHP,F is monoclinic [C2/c, a = 21.825(9) A, b = 3.811(5) A, c = 20.491(6) A, beta = 92.80(3)degrees, Z = 8]. The fundamental intermolecular and insignificant intramolecular hydrogen-bonded dimer structure of DMHP is maintained but is distorted and is supplemented by hydrogen bonds between the CO oxygen of each DMHP molecule and the OH group of one formic acid molecule [O-H...O; 0.99(5) A, 176(3)degrees, 1.53(4) A]. However, the two DMHP and the two formic acid molecules are twisted out of plane like the blades of a four-bladed propeller. DMHP,A is triclinic [P1, a = 8.458(2) A, b = 8.471(2) A, c = 6.986(3) A, alpha = 104.33(2)degrees, beta = 92.57(2)degrees, gamma = 88.78(2)degrees, Z = 2].(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1501074 TI - Identification of 5-ethyl-5-(2-methylbutyl)barbituric acid as an impurity of manufacture in amobarbital. AB - Amobarbital [5-ethyl-5-(3-methylbutyl)barbituric acid], USP, was found to contain an impurity that was not associated with hydrolysis and decomposition of the barbiturate ring. The impurity was isolated by semipreparative HPLC and was identified as 5-ethyl-5-(2-methylbutyl)barbituric acid (1) by MS (electron impact and chemical ionization) and 1H NMR. The substitution pattern on the alkyl side chain was verified by using the achiral NMR shift reagent tris(6,6,7,7,8,8,8 heptafluoro-2,2- dimethyl-3,5-octanedionato)europium(III). Older samples of amobarbital, USP, contained greater than 6% of 1, whereas recent samples of amobarbital, USP, contained less than 1% of 1. Because the pharmacological profiles of 1 and amobarbital in rodents are comparable, the impurity probably does not constitute a clinically significant problem for humans. PMID- 1501075 TI - Synthesis and antimicrobial and anti-inflammatory activities of substituted 2 mercapto-3-(N-aryl)pyrimido[5,4-c]cinnolin-4-(3H)-ones. AB - Ten new substituted 2-mercapto-3-(N-aryl)pyrimido[5,4-c]cinnolin-4- (3H)-ones (4) were prepared by refluxing substituted 4-aminocinnolin-3-carboxylic acid (3) with substituted arylisothiocyanate in anhydrous pyridine. These derivatives were evaluated for their antimicrobial and anti-inflammatory activities. Some of the title compounds possess potent antimicrobial activity. PMID- 1501076 TI - Nuclear magnetic resonance spectrometric investigations of calcium antagonist drugs. III: Conformational and dynamic features of diltiazem in solution. AB - Conformational features of diltiazem in D2O have been delineated by measuring 13C and 1H NMR parameters. The data obtained by interpretation of spin-lattice relaxation rates and 13C-[1H] nuclear Overhauser effects were used to build a model of the most probable arrangement in solution. The molecular motion of the two aromatic rings and of the thiazepinic ring is anisotropic, and the assumption that the molecule is an ellipsoid undergoing Brownian motion leads to calculation of the diffusion constants for the rotation around the longer axis and the shorter axis. The dimethylaminoethyl chain seems folded back, and it displays the typical features of segmental motion; in the same way, the methoxy- and the acetyloxymethyls behave like free rotors. PMID- 1501078 TI - Influence of in vitro test conditions on release of aspirin from commercial tablets. AB - The influence of in vitro test conditions on the release of aspirin from commercial tablets was assessed with a USP rotating-basket dissolution apparatus. Three types of aspirin tablets were evaluated: plain, buffered, and microencapsulated. The variables investigated were stirring speed, pH, and volume and temperature of the dissolution medium. Plain tablets gave the best dissolution profiles under all experimental conditions, except at pH 3. Microencapsulated tablets showed sustained release. For all three types of tablets, faster dissolution was observed at pH 4.5 compared with that in artificial gastric juices. Increasing the stirring rate increased the dissolution rate, an effect most pronounced for plain tablets. Very similar dissolution curves were obtained when the dissolution test was conducted in 500 and 900 mL of dissolution media regardless of the pH of the media. No significant difference in dissolution profiles was observed when the effect of temperature was investigated. The dissolution data were evaluated on the basis of theoretical dissolution equations and by linear transformation of dissolution curves. Highly significant linear correlation coefficients revealed that the cube root equation could be used to describe drug release in artificial gastric juices, regardless of tablet type. When pH 4.5 buffer solution was used as the dissolution medium, different kinetic models were applicable. PMID- 1501077 TI - Aminopyridine carbamic acid esters: synthesis and potential as acetylcholinesterase inhibitors and acetylcholine releasers. AB - 4-Amino-3-pyridyl carbamates (2a-c) were synthesized as potential acetylcholinesterase inhibitors and acetylcholine releasers on the basis of the reported activity of the analogous N-(4-amino-3-pyridyl)-N',N'-dimethylurea (1). Although 4-amino-3-pyridyl N,N-dimethylcarbamate (2b) showed good cholinesterase inhibition [concentration that elicited a 50% reduction in the maximal enzyme response (IC50) was 13.4 microM], it had no effect on the stimulated release of [3H]acetylcholine from rat striatal slices. 4-[[(Dimethylamino)methylene]amino]-3 pyridyl N,N-dimethylcarbamate (7a), an intermediate in the synthesis of 2b, demonstrated surprisingly good cholinesterase inhibition (IC50 was 9.4 microM) but showed no activity as a release. A precursor to 7a, N-(3-hydroxy-4-pyridyl) N',N'-dimethylformamidine (6a), showed some activity in release but was not an esterase inhibitor, whereas the precursor to 6a, 4-amino-3-pyridinol (5a), was a potent releaser. A new synthesis of 5a, based on an ortho-directed lithiation strategy, is also reported. PMID- 1501079 TI - Triazolines. XXI: Preformulation degradation kinetics and chemical stability of a novel triazoline anticonvulsant. AB - The effect of pH, temperature, and two buffer species (citric acid-phosphate and bicarbonate-carbonate) on the stability of 1-(4-chlorophenyl)-5-(4-pyridyl)-delta 2-1,2,3-triazoline (ADD17014; 1), a novel triazoline anticonvulsant, was determined by HPLC. One of the main degradation products of 1 at pH 7.0 was isolated by TLC and identified as the aziridine derivative by MS. Investigations were carried out over a range of pH (2.2-10.7) and buffer concentration [ionic strength (mu), 0.25-4.18] at 23 degrees C. The degradation followed buffer catalyzed, pseudo-first-order kinetics and was accelerated by a decrease in pH and an increase in temperature. The activation energy for the degradation in citric acid-phosphate buffer (pH 7.0 and constant ionic strength mu at 0.54) was 12.5 kcal/mol. General acid catalysis was observed at pH 7.0 in citric acid phosphate buffer. The salt effect on the degradation obeyed the modified Debye Huckel equation well; however, the observed charge product (ZAZB) value (2.69) deviated highly from the theoretical value (1.0), perhaps because of the high mu values (0.25-4.18) of the solutions used. The stability data will be useful in preformulation studies in the development of a stable, oral dosage form of 1. PMID- 1501080 TI - Photodegradation of nifedipine under aerobic conditions: evidence of formation of singlet oxygen and radical intermediate. PMID- 1501081 TI - Evaluation of methods for estimating the rate constant of a one-compartment absorption model when absorption and elimination rate constants are equal. PMID- 1501082 TI - Revisiting functional vision. PMID- 1501083 TI - Effect of posterior chamber intraocular lens design and surgical placement on postoperative outcome. AB - Intraocular lens (IOL) design, optical configuration, and placement have potential effects on postoperative outcome. Laboratory studies have suggested that one-piece, biconvex designs may reduce or delay posterior capsular opacification and that in-the-bag fixation of the posterior chamber IOL may reduce inflammation. To document the clinical significance of IOL design and placement, we conducted a randomized, prospective, clinical trial. Six hundred uncomplicated capsulorhexis and phacoemulsification patients were randomized in a three-factor design to receive an IOL that was one-piece or three-piece, had a biconvex, plano-convex, or laser ridge optic, and was bag-or sulcus-fixated. Treatment differences were related to lens placement. Patients with bag-fixated IOLs had less posterior capsular opacification, fewer YAG laser capsulotomies, a higher percentage of centered lenses, less inflammation, and fewer late posterior capsular striae than those with sulcus-fixated IOLs. In the latter group, patients with three-piece IOLs had fewer posterior capsular striae at three months postoperatively. All six occurrences of haptic loop distortion were in patients with three-piece IOLs. Patients with the one-piece design had less late inflammation than those with the three-piece design. Fewer YAG capsulotomies were necessary at one year in patients with the biconvex design than in those with the plano-convex or laser ridge configurations. Operative complications, endothelial cell loss, and postoperative complications were not IOL-related. PMID- 1501084 TI - Comparison of the accuracy and reproducibility of the keratometer and the EyeSys Corneal Analysis System Model I. AB - The EyeSys Corneal Analysis System Model I measures corneal topography using digital image analysis of placido rings reflected off the cornea. With three observers, we compared the accuracy and reproducibility (precision) of the Marco Keratometer Model 1 and EyeSys Corneal Analysis System Model I using four poly(methyl methacrylate) spheres (37.50, 42.51, 47.54, and 55.06 diopters [D]), three steel spheres (40.50, 42.50, and 44.75 D), and 20 normal human eyes (41.50 to 46.00 D). For the spheres, the standard deviations of intra-observer and overall reproducibility for both devices were less than 0.12 D; the absolute mean differences between the measurements of the seven spheres and the known values were 0.25 D or more for two spheres as measured by the keratometer and none as measured by the EyeSys. For the normal corneas, the standard deviations of intra observer and overall reproducibility for dioptric measurements were 0.07 D and 0.14 D for the keratometer and 0.13 D and 0.19 D for the EyeSys. The EyeSys Corneal Analysis System Model I exceeds keratometer accuracy in reading calibrated spheres and approaches keratometer reproducibility in measuring the 3 mm zone of normal human corneas. PMID- 1501085 TI - Pupil diameter and the principal ray. AB - Placement of the surgical zone is critical in refractive procedures that alter a portion of the corneal curve. An improperly centered optical zone may produce glare, decrease best corrected visual acuity, and decrease contrast sensitivity. For proper placement, the new surface should be centered around the line of sight, which is the principal ray from the object of regard that passes through the image of the patient's pupil as projected on the cornea. This point is not necessarily at the geometric center of the cornea and is found by locating the center of the pupil while the patient is maintaining fixation coaxially with the surgeon. However, the pupil does not dilate concentrically and its geometric center moves as the pupil diameter changes. We have found a shift up to 0.7 mm in the geometric center of the pupil as it dilates. Therefore, centration of an ablated or a radial keratotomy zone is most efficiently done when the diameter of the modified corneal optical zone is centered around the line of sight and is superimposed upon the entrance pupil. This will minimize extension of the edge of the large pupil beyond the ablated zone and reduce unwanted secondary optical effects from degrading vision. PMID- 1501086 TI - Incidence of retinal detachment following Nd:YAG capsulotomy after cataract surgery. AB - In a retrospective study, we reviewed 218 consecutive Nd:YAG laser posterior capsulotomies performed at the Gimbel Eye Centre between June 1987 and November 1989 for the incidence of retinal detachment (RD) following treatment. Matched controls were found for 198 YAG cases. The median post-surgical follow-up for the YAG cases was 49.5 months; for the controls, 50.0 months. The median time between cataract extraction and YAG laser posterior capsulotomy was 24.8 months. The median follow-up after YAG was 24.2 months. Two of the 198 YAG cases (1.0%) and one of the 198 controls (0.5%) had RD. In the YAG cases, RD occurred 54.8 and 36.5 months after cataract surgery; in the control cases, 51.8 months after cataract surgery. Retinal detachment occurred at 15.0 and 17.0 months after YAG capsulotomy. These rates were lower than those reported in the literature. We feel that the surgical techniques of continuous circular capsulorhexis and in-the bag IOL placement reduce the risk of RD following Nd:YAG posterior capsulotomy. PMID- 1501087 TI - Postsurgical inflammation after phacoemulsification and extracapsular extraction with soft or conventional intraocular lens implantation. AB - A one-year prospective study was conducted in 120 patients to assess the time course of changes in intraocular inflammation after three cataract surgery procedures: planned extracapsular extraction with poly(methyl methacrylate) (PMMA) intraocular lens (IOL) implantation (11 mm incision group), phacoemulsification with PMMA IOL implantation (7 mm incision group), and phacoemulsification with foldable silicone single-piece IOL implantation (4 mm incision group). Each group was carefully matched for patients' ophthalmologic and systemic backgrounds. Patients with hard nuclei were excluded. The degree of inflammation was evaluated by quantitating aqueous flare intensity and cell count with the laser flare-cell meter. In the early postoperative period, both aqueous flare intensity and cell count were highest in the 11 mm incision group followed, in decreasing order, by the 7 mm and 4 mm incision groups. Significant between group differences were observed at one, two, and seven postoperative days for flare and one day through one week for cells. Both parameters in each group decreased to a similar level one month after surgery, but flare intensity in all groups remained significantly higher than that of age-matched normal controls up to six months postoperatively. PMID- 1501088 TI - Phacoemulsification and modified trabeculectomy for managing combined cataracts and glaucoma. AB - Seven eyes in four patients who had combined cataract extraction, intraocular lens implantation, and glaucoma filtering surgery were examined retrospectively. A phacoemulsification technique was used with trabeculectomy performed under a modified limbal flap. All patients achieved a final visual acuity of 20/40 or better and intraocular pressure of less than 20 mm Hg without medication. The techniques are described and the management of combined cataracts and glaucoma is discussed. PMID- 1501089 TI - Early posterior capsular opacification after intercapsular cataract extraction and rigid Galand disc intraocular lens implantation. AB - From retrospective studies of implantation of the rigid Galand disc intraocular lens (IOL) and the Sinskey style J-loop IOL, we found that posterior capsular opacification was more common and developed faster in eyes implanted with a Galand disc IOL than in eyes implanted with a Sinskey style J-loop IOL. We investigated this further in a clinical study of 20 patients implanted with a Galand disc IOL. We found a specific type of posterior capsular haze, resembling a "moon landscape," in 10 (50%) of the 16 eyes (80%) with capsular fibrosis. PMID- 1501090 TI - Combined myopia and astigmatism surgery. Review of 350 cases. AB - Between February 1985 and December 1987, 350 eyes had combined radial keratotomy and transverse keratotomy surgery. All procedures were performed by the same surgeon. The number and length of the radial and transverse incisions were varied according to the surgeon's clinical judgment based on his personal experience and the nomograms developed by Thornton. Our results showed that 93% of the eyes had 20/40 or better uncorrected visual acuity at the last follow-up visit. The data indicate that quantifiably predictable results can be achieved with this procedure and that results appear stable up to five years after surgery in 80% of the documented cases. There was a tendency toward increasing effect of the transverse incisions in 20% of cases studied. This seems to correlate well with previous studies measuring long-term results with radial incisions for myopia. PMID- 1501091 TI - Maximal mydriasis evaluation in cataract surgery. AB - We propose the maximal mydriasis test (MMT) as a simple and safe means to provide the cataract surgeon with objective and dependable preoperative information on the idiosyncratic mydriatic response of the pupil. The MMT results of a consecutive series of 165 eyes from 100 adults referred for cataract evaluation are presented to illustrate the test's practical applications and value. The results enable the surgeon to anticipate problem eyes preoperatively so he or she can plan an appropriate and effective surgical strategy. The MMT has also improved out cost-effectiveness by cutting down unnecessary delays in the operating room and enabling better utilization of restricted costly resources. PMID- 1501092 TI - Use of grafts smaller than the opening for keratoconic myopia and astigmatism. A prospective study. AB - A prospective study was conducted on 15 consecutive keratoconic eyes to evaluate the use of grafts smaller than the opening in keratoconic myopia and astigmatism. All surgeries were performed by the senior author. Average age of the patients was 41.1 years. Average follow-up was 1.6 years. After all sutures were removed, results showed an average decrease in myopia of 13.24 diopters (D) (range 1.75 to 23.25) principally from corneal flattening and a small reduction in axial length. Average postoperative spherical equivalent was -2.17 D (range +1.50 to -7.25). The average postoperative astigmatism was 3.78 D (range 1.75 to 6.00). This study and a previous retrospective study suggest that the use of grafts 0.25 mm smaller than the opening, i.e., 7.50/7.75 mm, for penetrating keratoplasty in keratoconus is justified. PMID- 1501093 TI - Quantification of the reduction of glare disability after standard extracapsular cataract surgery. AB - Glare disability is often cited as an indication for cataract extraction, but very little objective data exist showing improvement of glare disability following standard extracapsular cataract extraction with posterior chamber intraocular lens implantation. In a series of 25 patients we determined glare disability by the reduction in visual acuity with dim room lighting (baseline) and with full room lights; with the brightness acuity tester (BAT) on low, medium, and high; with the true vision analyzer (TVA) glare light. Glare disability was quantified by the difference between the log VA postoperatively and the log VA preoperatively. Glare disability with BAT medium was no different than that with bright room lights (P greater than .05). Glare disability with BAT high was greater than that with BAT medium (P less than .01) but did not differ from that with TVA (P greater than .05). Glare disability was significantly reduced (P less than .01) six weeks postoperatively as measured by all tests except BAT low. Cataract surgery can be expected to reduce glare disability as measured by these tests. PMID- 1501094 TI - Measurement of glare disability using an automated perimeter. AB - We have developed a new system to measure glare disability spatially and quantitatively using an Octopus 500E automated perimeter with an attached glare source. We describe the method used for measuring glare disability with this system and the results in cataracts and pseudophakia with and without various postoperative complications. PMID- 1501095 TI - In vitro evaluation of biocompatibility of surface-modified poly(methyl methacrylate) plate with rabbit lens epithelial cells. AB - Collagen type I was immobilized onto a poly(methyl methacrylate) (PMMA) plate by covalent bonding following surface modification by two methods. One method introduced amino groups by aminolysis with N-lithioethylenediamine (PMMA-NH2) and the other introduced carboxyl groups by graft copolymerization of acrylic acid (AAc) and acrylamide (AAm) (PMMA-COOH). Lens epithelial rabbit cells were cultured on the PMMA plate which was immobilized with collagen. Polygonal cells with a mosaic appearance were observed on the PMMA-COOH plate immobilized with collagen type I, whereas pleomorphic cells were present on the virgin PMMA and on the PMMA-NH2 plate immobilized with collagen type I. We concluded the PMMA-COOH plate immobilized with collagen type I provided a more comfortable atmosphere for lens epithelial cells, causing no metaplasia, than the other plates used in this cell culture model experiment. PMID- 1501096 TI - Accelerated hydrolytic and ultraviolet aging studies on SI-18NB and SI-20NB silicone lenses. AB - This report describes the results of in vitro accelerated hydrolytic and ultraviolet aging studies performed on SI-18NB and SI-20NB silicone intraocular lenses. The hydrolytic aging study simulated the effects of 20 years in vivo. The ultraviolet aging study simulated the effects of 17 years in vivo. No significant changes in the focal length and resolution of the lenses were observed. Examination of the lens surfaces using scanning electron microscopy revealed no changes in surface morphology. PMID- 1501097 TI - Radial keratotomy in a patient with keratoconus. AB - A 30-year-old white male with keratoconus had uneventful radial keratotomy in his right eye. Although a good initial response was obtained with total correction of myopia and astigmatism, by 18 months postoperatively the entire result had regressed and the patient demonstrated reformation of the cone and regression to high myopia. Scarring occurred in the three inferior cuts overlying the cone. Cuts on the horizontal axis, and superiorly (above the cone), had a normal appearance with normal wound healing. Because of the nature of the wound healing overlying the portion of the cornea affected by the keratoconus and because of the total regression of effect, radial keratotomy in patients with keratoconus does not appear to be an effective modality. PMID- 1501098 TI - Braverman-Bechert nucleus rotator. PMID- 1501099 TI - Demagnetizer for ophthalmic surgical instruments. PMID- 1501100 TI - Consultation section. A 66-year-old male had complicated phacoemulsification with capsular bag placement of a multipiece posterior chamber lens with polypropylene loop supports. PMID- 1501101 TI - Refractive surgery and informed consent. Radial keratotomy with small optical zone hexagonal keratotomy. PMID- 1501102 TI - Inflammatory sequelae with silicone-polypropylene IOLs. PMID- 1501103 TI - Capsular rupture at hydrodissection. PMID- 1501104 TI - Removal of viscoelastics. PMID- 1501105 TI - Are lens exchanges and "T" cuts obsolete? PMID- 1501106 TI - Inflammation after lens implantation. PMID- 1501107 TI - Temporary wound closure. PMID- 1501108 TI - Revolutions in the evolution of dentistry. PMID- 1501109 TI - The binding properties of the solubilized sulfonylurea receptor from a pancreatic B-cell line are modulated by the Mg(++)-complex of ATP. AB - Previous studies demonstrated that the Mg complex of ATP decreases glyburide- and increases diazoxide-binding to membranes from pancreatic islets. To examine further the mechanism of these effects, the sulfonylurea receptors in microsomes of the hamster B-cell line HIT-T15 were solubilized with detergents. Maximum recovery of receptors (40%) was obtained with Triton X-100. Specific binding of [3H]glyburide to the solubilized receptors (Kd = 0.35 nM, maximum number of binding sites = 170 fmol/mg of protein) corresponded well to specific binding to microsomes. In Triton X-100 extracts, MgATP (300 microM) reduced the number of high-affinity sites for [3H]glyburide by 50% and increased the dissociation constant for [3H]glyburide by 4-fold; MgATP was half-maximally effective at 20 microM. Development of MgATP-induced inhibition of [3H]glyburide binding to solubilized binding sites was not slower than dissociation of [3H]glyburide binding. Alkaline phosphatase accelerated the reversal of MgATP-induced inhibition of [3H]glyburide binding. In the presence of Mg++, not only ATP but also ADP, GTP and GDP inhibited [3H]glyburide binding to the solubilized receptor. However, MgADP did not inhibit [3H]glyburide binding when the MgATP concentration was kept low by the hexokinase reaction. MgATP significantly enhanced diazoxide-induced displacement of [3H]glyburide from the solubilized receptor. The MgATP-induced inhibition of binding was weakened by millimolar concentrations of free ATP. It is concluded that the binding sites for MgATP, glyburide and diazoxide are located at a single protein or at closely associated proteins which may include a protein kinase. PMID- 1501110 TI - Time-dependent effects of dexamethasone administration on the suppression of plasma hydrocortisone, assessed with a pharmacokinetic model. AB - The influence of the time of dexamethasone (DEX) administration (0.5 mg i.v.) on the suppression of plasma hydrocortisone (HC) was investigated in six healthy subjects, by comparing dosage times of 8 and 20 hr. To estimate HC production after DEX administration a pharmacokinetic model was developed and applied to the time course of plasma HC. This model was based on the assumption that HC production could be described as a continuous i.v. infusion, that stops and starts instantaneously. After DEX at 8 hr, HC production was reduced instantaneously to a minimum level and HC disappeared rapidly from plasma with an elimination half-life of 1.32 +/- 0.28 hr (mean +/- S.D.). Almost complete suppression of HC production lasted for 20 hr. The nocturnal increase in HC production at 20 hr after DEX administration was still attenuated compared to the preceding night. After DEX administration at 20 hr, plasma HC was lower than control for about 20 hr, but it was not reduced to the very low level observed after DEX dosage in the morning. Approximately 20 hr after dosage of DEX at 20 hr, HC production seemed to follow the normal diurnal variation of the control values again. To explain the difference in HC suppression by DEX at different dosage times, we constructed a curve describing the relationship between DEX concentration and suppression of the sudden increase in HC production during the night. This curve indicates that HC suppression by DEX could be completely dependent on DEX concentration, without a DEX independent circadian variation. PMID- 1501111 TI - Kinetic-dynamic modeling of lymphocytopenia induced by the combined action of dexamethasone and hydrocortisone in humans, after inhalation and intravenous administration of dexamethasone. AB - Ten healthy male volunteers received 5 mg of dexamethasone sodium phosphate (DEX) i.v. and, on an other occasion, by way of nebulization. Plasma DEX and hydrocortisone (HC) concentrations as well as blood lymphocyte count (BLC) were monitored over 12 hr and at 24 to 28 hr after DEX administration. Bioavailability of DEX after inhalation was about 27% of DEX i.v. DEX-induced depletion of plasma HC could be predicted with a pharmacokinetic model. The reonset rate of HC production was dependent of DEX dose. BLCs declined after DEX administration, reaching a minimum between 4- and 8-hr postdosing. The DEX- and HC-induced depression of BLC could be described by an integrated pharmacokinetic pharmacodynamic competitive-interaction model that assumes that both agonists act on the same receptor. With this model the potency and efficacy of DEX and HC with respect to lymphocytopenia could be estimated simultaneously. The potency of DEX was 10 times greater than the potency of HC. The estimated efficacy suggests that HC is only a partial agonist; the maximal lymphocytopenic effect (Emax) of HC was estimated at 80% (27-99%) of the efficacy of DEX. Our results indicate that DEX should be preferred instead of HC in conditions in which the lymphocytopenic effect is the primary systemic corticosteroid treatment goal. PMID- 1501112 TI - Effects of perindopril on myocardial inotropy, lusitropy and economy, and on diaphragmatic contractility in the cardiomyopathic Syrian hamster. AB - Over a 5-month period, 22 1-month-old cardiomyopathic Syrian hamsters were randomly treated with either angiotensin-converting enzyme inhibitor (perindopril 1 mg/kg/day) (PE, n = 11) or placebo (PL, n = 11), and 7 age-matched controls (C) were given placebo. Compared to C, mechanics of left ventricular papillary muscles from PL exhibited a lower maximum unloaded shortening velocity (Vmax) (P less than .01) and normalized peak active force (P less than .05), and a significantly less curved shape of the force-velocity (F-V) relationship (P less than .01). The curvature of the F-V relationship has been proposed as a reflection of the efficiency of muscle contraction. Compared to PL, PE had a 68% inhibition of plasma ACE activity and a greater Vmax (P less than .05), whereas active force (AF) was similar. This resulted in a lesser decrease of the curvature of the F-V relationship compared to that of C (P less than .05). Muscle strips from the ventral costal diaphragm were dissected from the muscle in situ. In both twitch and tetanus modes, intrinsic mechanical performance of diaphragm muscle was markedly decreased in PL compared to C as regards normalized positive (+dF/dtmax/mm2) and negative (-dF/dtmax/mm2) peak rate of force, and normalized peak active force (AF/mm2) (P less than .01 each). In both twitch and tetanus modes, PE had an increased +dF/dtmax/mm2 (P less than .05), -dF/dtmax/mm2 and AF/mm2 (P less than .01 each), compared to PL. These results indicate 1) that the low inotropic state observed in cardiomyopathic Syrian hamsters was associated with decreased myothermal economy of cardiac contraction and with a major impairment of diaphragm intrinsic contractility, and 2) that early therapy with angiotensin-converting enzyme inhibitor helped to preserve myocardial contractility and economy, and diaphragm contractility. PMID- 1501113 TI - Adenosine 5'-(2-fluorodiphosphate) is not a selective P2Y purinoceptor agonist in the rabbit jugular vein. AB - The relaxant properties of the putative selective P2Y agonist adenosine 5'-(2 fluorodiphosphate) (ADP-beta-F) and its structural analog adenosine 5'-(2 thiodiphosphate) have been investigated in the rabbit precontracted jugular vein preparation. In tissues with intact endothelium, ADP-beta-F produced a multiphasic agonist concentration/effect curve made up of two vasorelaxant components which were kinetically and pharmacologically distinct. The higher potency phase (p[A50] 5.58 +/- 0.13), characterized by slow, tonic responses, was retained after endothelial denudation and blocked by the selective P1 purinoceptor antagonist 8-sulphophenyltheophylline. The lower potency phase (p[A50] 3.98 +/- 0.07), characterized by fast, phasic responses, was abolished by endothelial denudation and is presumed to be mediated at P2Y purinoceptors. By contrast, the agonist concentration/effect curve to adenosine 5'-(2 dithiophosphate) in endothelium-intact tissues appear monophasic and was unaffected by 8-sulphophenyltheophylline (p[A50] 6.86 +/- 0.12), although endothelial denudation revealed a secondary P1-induced relaxant component (p[A50] 5.73 +/- 0.20). This study demonstrates that in the rabbit jugular vein, relaxant responses to ADP-beta-F are mediated primarily by activation of P1 purinoceptors, and it is, therefore, invalid to regard ADP-beta-F as a selective probe for P2Y purinoceptors, whereas adenosine 5'-(2-thiodiphosphate) does show some selectivity for this receptor. PMID- 1501114 TI - The antihypertensive effect of the angiotensin II receptor antagonist DuP 753 may not be due solely to angiotensin II receptor antagonism. AB - The angiotensin II (AII) receptor antagonist, DuP 753 (10 mg/kg intraduodenal), produced a sustained and long-lasting antihypertensive effect in conscious renin dependent hypertensive rats. Blood pressures were still reduced markedly 24 to 72 hr after administration of a single dose of DuP 753. However, pressor responses elicited by either angiotensin I or AII were not blocked at these times despite the continued antihypertensive effect of DuP 753. In a model of orthostatic hypotension, DuP 753 and the selective alpha-1 adrenoceptor antagonist prazosin produced a marked orthostatic hypotension response in renin-dependent hypertensive rats as demonstrated by potentiation of the decrease in blood pressure induced by a 90 degrees tilt. The nonpeptide AII receptor antagonist SK&F 108566 (10 mg/kg intraduodenal) did not produce orthostatic hypotension and the angiotensin converting enzyme inhibitor enalapril produced only a slight orthostatic response to tilting. In conscious spontaneously hypertensive rats (SHR), allowed 3 to 4 days to recover from surgery, administration of either enalapril (1 mg/kg i.v.) or SK&F 108566 (10 mg/kg i.v.) did not significantly effect blood pressure. In SHR tested within 24 hr of surgery, enalapril was effective in lowering blood pressure. In contrast, in surgically recovered SHR, DuP 753 (10 mg/kg i.v.) produced an antihypertensive effect that was slow in onset, sustained and extremely long in duration. Blood pressures did not return to predrug levels until 48 hr after administration of DuP 753. Stimulation of the thoracolumbar sympathetic outflow in pithed rats produced frequency-dependent pressor responses that were significantly potentiated by continuous infusion of a subpressor dose of AII.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1501115 TI - Cardiovascular effects of cocaine in conscious rats: relative significance of central sympathetic stimulation and peripheral neuronal monoamine uptake and release mechanisms. AB - Cocaine (0.03-3 mg/kg, i.v.) produced a dose-dependent increase in mean arterial blood pressure and heart rate in conscious Sprague-Dawley rats. Pretreatment with the competitive ganglionic blockers pentolinium or hexamethonium attenuated cocaine's pressor effect, whereas noncompetitive (chlorisondamine) or mixed (mecamylamine) type blockers not only abolished, but also reversed it to a depressor effect. Cocaine's tachycardiac effect was attenuated by all four ganglionic blockers. The relative effectiveness of the four ganglionic blockers in antagonizing cocaine-induced cardiovascular effects was similar to that of antagonism of phenylephrine-induced, centrally mediated reflex bradycardia. All four ganglionic blockers at all the doses tested produced similar reductions in base-line BP, thereby suggesting that these agents produced similar degrees of maximal reduction of basal sympathetic tone. The pressor responses to norepinephrine (0.2 micrograms/kg) were potentiated, whereas those to tyramine (0.3 mg/kg) were inhibited by cocaine (0.3-3 mg/kg); the former effect was not dose dependent (bell-shaped dose-response curve), whereas the latter effect was dose-dependent. The amine uptake inhibitory potency (ED50, 0.85 mg/kg) of cocaine is about 10 times less than its potency to produce pressor (ED50, 0.075 mg/kg) and tachycardiac (ED50, 0.083 mg/kg) effects. Chlorisondamine did not antagonize the pressor effects of the indirect sympathomimetic agent, tyramine. These results suggest that the blockade of cocaine's pressor and tachycardiac effects by ganglionic blockers is not related to their ability to eliminate basal sympathetic tone and, thereby, indirectly blunt cocaine's inhibitory effect on sympathetic neuronal uptake of norepinephrine. Rather, the results indicate that these effects are mainly due to their antagonistic actions on cocaine-induced central stimulation of sympathetic activity.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1501116 TI - Pharmacokinetics and pharmacodynamics of labetalol in the pregnant sheep. AB - The maternal-fetal disposition of labetalol, a combined alpha-1 and beta adrenergic blocker, and its pharmacodynamics in pregnancy are not well understood. This study describes the pharmacokinetics, cardiovascular and metabolic effects of labetalol in the mother and in utero fetus after a 100-mg maternal i.v. bolus administration, in the chronically instrumented pregnant sheep. Labetalol shows a triexponential decline in the mother with a total body clearance of 30.8 +/- 3.83 ml/min/kg, an apparent steady-state volume of distribution (nonparametric) of 3.02 +/- 0.18 liters/kg and terminal elimination half-life of 2.79 +/- 0.66 hr. These estimates are similar to the reported values in pregnant women. Labetalol rapidly crosses the sheep placenta. The peak fetal plasma concentration was 33.7 +/- 5.8 ng/ml, the fetal exposure to labetalol as calculated by the fetal to maternal area under the curve ratio was 14.37 +/- 1.54% and the apparent fetal elimination half-life was 3.71 +/- 0.5 hr. Labetalol persists in the amniotic and fetal tracheal fluids up to 24 hr with concentrations reaching 2- to 4 times the fetal plasma concentration. Whereas there were no significant maternal or fetal cardiovascular effects, some very significant metabolic effects were observed, including fetal and maternal lactic acidosis and hyperglycemia. Lactic acid accumulates in the fetal blood and amniotic fluid with peak concentrations (6.0 +/- 0.31 and 5.5 +/- 0.26 mM, respectively) showing a more than 300% increase over control values. The exact mechanism by which labetalol causes these metabolic effects is not clear, but it may involve its partial beta-2 agonist activity. PMID- 1501117 TI - Behavioral evidence for differential adaptation of the serotonergic system after acute and chronic treatment with (+/- )-1-(2,5-dimethoxy-4-iodophenyl)-2 aminopropane (DOI) or ketanserin. AB - The 5-hydroxytryptamine (5-HT)2 agonist (+/- )-1-(2,5-dimethoxy-4-iodophenyl)-2 aminopropane (DOI) and antagonist ketanserin were evaluated for acute and chronic effects on the 5-HT2 receptor-mediated head-twitch response (HTR) in mice. A single dose of DOI resulted in tolerance to the DOI-induced HTR at 24 hr but supersensitivity at 48 hr. This apparent supersensitivity persisted up to 144 hr after the first DOI injection. Chronic once daily DOI administration significantly reduced the HTR frequency (days 2-6), which then returned slowly to control levels by treatment day 13. A 48-hr withdrawal from this chronic regimen produced a similar supersensitivity to that observed after a single DOI injection upon a 48-hr challenge. This effect also persisted up to 144 hr after cessation of chronic treatment. Acute pretreatment with a single injection of ketanserin significantly reduced the DOI-induced HTR frequency when tested 24 and 48 hr, but not 120 hr, after injection of the antagonist. After withdrawal from chronic ketanserin treatment, the DOI-induced HTR was significantly reduced at 24 hr but significantly increased at 48 hr. This enhanced effect subsided when mice were tested with DOI 72 hr after cessation of chronic antagonist treatment. These data suggest that the serotonergic system adapts to chronic exposure of either agonists or antagonists in a fashion distinctly different from that exhibited by other monoamine neurotransmitter systems. PMID- 1501118 TI - Subjective and behavioral effects of diphenhydramine, lorazepam and methocarbamol: evaluation of abuse liability. AB - The effects of orally administered placebo, diphenhydramine, lorazepam, methocarbamol and placebo were studied in volunteers with histories of recreational substance abuse including sedative/hypnotics. Placebo, diphenhydramine (100, 200 and 400 mg), lorazepam (1 and 4 mg) and methocarbamol (2.25 and 9 g) were tested in a randomized, double-blind crossover study using 14 subjects. Psychomotor and cognitive performance and subject- and observer-rated responses were measured daily before and for 5.5 hr after drug administration. The results showed that each of the drugs exhibited a different profile of effects on the test battery. Lorazepam produced significant increases in subjects' ratings of drug effect and liking, increases in measures of sedation and impairment of psychomotor performance. Methocarbamol also produced significant increases in subjects' ratings of drug effect and liking and measures of sedation, but it produced only minor impairment of psychomotor and cognitive performance. Diphenhydramine increased subjects' and observers' ratings of drug effect and measures of sedation, but it produced less psychomotor performance impairment and liking than lorazepam. Diphenhydramine produced the most side effects. The present study clearly differentiated the behavioral and subjective profiles of diphenhydramine, lorazepam and methocarbamol. Consistent with its recognized low abuse liability, diphenhydramine produced fewer increases in measures of positive mood and more adverse effects. The considerable overlap in subjective effect measures of positive mood make further differentiation with respect to abuse liability difficult. PMID- 1501119 TI - Influence of epithelium on the reactivity of guinea pig isolated, perfused trachea to bronchoactive drugs. AB - The mechanisms by which the epithelium affects reactivity of guinea pig trachealis to agonists were examined using the isolated, perfused trachea preparation. Contractile agonists (acetylcholine, methacholine, carbachol or histamine) were more potent when applied to the serosal (extraluminal, EL) surface compared to the mucosal (intraluminal, IL) surface, and the IL maximum responses to these agents were smaller. In epithelium-denuded tracheae, IL reactivity to the agonists was increased to the EL level. Physostigmine (10(-7) M) increased the EL and IL potency of acetylcholine to that of carbachol (+/- epithelium), and elevated the IL acetylcholine maximum response (+ epithelium); the relative role of epithelial acetylcholinesterase could not be defined. Indomethacin (3 x 10(-6) M) increased, in an epithelium-dependent manner, the IL acetylcholine, carbachol and histamine maximum responses to the EL level. Phentolamine plus propranolol (both 10(-6) M) potentiated the IL maximum response to methacholine, Isoproterenol also was more potent extraluminally than intraluminally, and the EL and IL maximum responses were similar. IL isoproterenol reactivity was elevated to the EL level in rubbed tracheae. Corticosterone (5 x 10(-5) M) potentiated EL and IL responses to isoproterenol (+/- epithelium); the relative role of epithelial extraneuronal uptake could not be delineated. The epithelium reduces reactivity to mucosally applied drugs by acting as a diffusion barrier. In addition, responses to mucosally administered contractile agonists are inhibited by a physiological antagonism caused by modulatory prostanoids, catecholamines and, possibly, epithelium-derived relaxing factor. PMID- 1501120 TI - Tolerance, cross-tolerance and withdrawal in rats made dependent on diazepam. AB - Rats were trained to discriminate pentylenetetrazole (PTZ; 20 mg/kg) from midazolam (MDZ; 1 mg/kg) and from saline using a three-lever food-reinforced choice task. Using a cumulative dosing procedure, PTZ substituted for PTZ, and MDZ, chlordiazepoxide and diazepam (DZP) substituted for MDZ, in a dose-dependent manner. The animals were then treated with chronic DZP (20 mg/kg/8 hr for 7 days); 24 hr after the last dose of this regimen, the dose-effect curve of DZP was redetermined. The ED50 for the discrimination of DZP increased 4.8-fold after chronic DZP. In a second group of subjects trained on this discrimination and treated with DZP (20 mg/kg/8 hr for 7 days), the ED50 for the discrimination of MDZ was increased 2.2-fold. After 14 days of recovery, the MDZ dose-effect curve shifted back to the left and was not significantly different from the ED50 value obtained before chronic DZP treatment. When the benzodiazepine antagonist flumazenil was tested in a cumulative manner (1.0-32.0 mg/kg), the animals selected the saline lever. Analogous to the previous chronic dosing regimen, DZP (20 mg/kg/8 hr/7 days) was then administered, and a combination of three tests were then given at 1, 2, 4, 7, 10 and 14 days after the last DZP treatment. On each of these days, a saline test was given first; it was followed by a DZP (2.5 mg/kg) test; which was then followed by a flumazenil (32.0 mg/kg) test. On the 1st day of testing, tolerance was seen to DZP and precipitated withdrawal (PTZ lever selection) was seen with flumazenil.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1501121 TI - Biochemical and pharmacological properties of SR 46349B, a new potent and selective 5-hydroxytryptamine2 receptor antagonist. AB - A new potent, selective and p.o. active serotonergic [5-hydroxytryptamine (5 HT2)] receptor antagonist, SR 46349B [trans, 4-([3Z)3-(2 dimethylaminoethyl)oxyimino-3(2-flurophenyl++ +)propen-1-yl]phenol hemifumarate) has been characterized by a series of "in vitro" and "in vivo" methods. Based upon binding studies with 5-HT2 receptors in rat brain cortical membranes and blockade of 5-HT-induced contractions in isolated tissues (rabbit thoracic aorta, rat jugular vein, rat caudal artery, rat uterus and guinea pig trachea), SR 46349B showed high affinity for 5-HT2 receptors. Furthermore, SR 46349B displayed moderate affinity for the 5-HT1C receptor and had no affinity for the other 5-HT1 subclass (5-HT1A, 5-HT1B or 5-HT1D), dopamine (D1 or D2), "alpha" adrenergic (alpha-1 or alpha-2), sodium and calcium channel and histamine (H1) receptors. It did not interact with histamine (H1), alpha-1 adrenergic and 5-HT3 receptors in smooth muscle preparations. No inhibition of the uptake of norepinephrine, dopamine or 5-HT was seen. Based upon blockade of pressor responses to 5-HT in pithed rats and in vivo binding studies in mice, SR 46349B was found to be a potent and p.o. active 5-HT2 receptor antagonist with a relatively long duration of action. Behavioral experiments, including mescaline- and 5-hydroxytryptophan induced head twitches and learned helplessness, as well as sleep-waking cycle and EEG spectral parameter studies, indicated that SR 46349B has a classical 5-HT2 psychopharmacological antagonist profile. PMID- 1501122 TI - Effect of amineptine on regional extracellular concentrations of dopamine and noradrenaline in the rat brain. AB - The effect of amineptine (1.25-20 mg/kg i.p.), an antidepressant inhibiting dopamine uptake, on extracellular concentrations of dopamine was studied in the rat striatum and nucleus accumbens by using the microdialysis technique and two Ca++ concentrations (1.26 and 3.4 mM) in the perfusion medium. In one experiment the effect of amineptine was studied on extracellular concentrations of dopamine and noradrenaline in the frontal cortex perfused with a medium containing 1.26 mM Ca++. Basal extracellular concentrations of dopamine in the striatum and nucleus accumbens were significantly higher at 3.4 mM Ca++. At 5 to 20 mg/kg, amineptine dose-dependently increased extracellular dopamine in the striatum and nucleus accumbens. No differences were found in the effect of amineptine in the two brain regions at the two calcium concentrations. When extracellular dopamine was expressed as a percentage of basal values, amineptine (20 mg/kg) caused greater increases in rats perfused with 1.26 mM Ca++ than in rats perfused with 3.4 mM Ca++ in both brain regions. A similar effect was found when 10 microM amineptine was infused through the dialysis fiber. The effect of 10 mg/kg i.p. of amineptine on dopamine output in the two brain regions was prevented by infusing 1 microM tetrodotoxin in the dialysis fiber. In the frontal cortex, 10 and 20 mg/kg of amineptine significantly raised dopamine and noradrenaline concentrations, whereas 5 mg/kg only increased noradrenaline output significantly. At 10 mg/kg i.p., amineptine also increased extracellular noradrenaline in the dorsal hippocampus. Amineptine had no consistent effects on the concentrations of dihydroxyphenylacetic acid and homovanillic acid in the various brain regions.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1501123 TI - Voltage- and time-dependent block of the delayed K+ current in cardiac myocytes by dofetilide. AB - The delayed K+ current (ik) and its change by dofetilide was studied in single myocytes from the guinea pig and rabbit heart using the two-electrode voltage clamp technique. In rabbit myocytes, ik consisted of only one component (Kr), which developed for moderate depolarizations and with a fast time course. In guinea pig myocytes, activation consisted of a rapid and a slow component, and the latter (Ks) only became manifest for depolarizations positive to 0 mV. Ks was resistant to block by dofetilide. Kr, however, was very sensitive: Kd 3.9 x 10( 9) M, Hill coefficient 2.0 (n = 5). The effect was voltage-dependent block increasing at depolarized levels. Block development was time dependent and occurred in two phases: a first fast and voltage-dependent phase was followed by a second much slower phase (time constant of 4.4 +/- 0.48 sec (n = 11). Recovery from block was slower as the membrane potential became more negative. This resulted in the absence of a steady-state frequency-dependent effect at negative membrane potentials. It is concluded that dofetilide is an efficient blocker of the fast component of ik. The block, as well as recovery, are voltage and time dependent. Block is greater at more depolarized levels, recovery is slower at more hyperpolarized levels. PMID- 1501124 TI - Accumulation of boron-10 (10B) in cell cultures exposed to mercaptododecaborate (Na2H(11)10B12SH) used for the neutron capture therapy of brain tumors. AB - Toxicity of mercaptoundecahydro-closo-dodecaborate (MHB, Na2H(11)10B12SH) and accumulation of MHB-derived 10B were studied in E7 neuroblastoma, C6 glioma, HeLa cells and embryonic lung LEP 19 fibroblasts in culture in exponential and stationary phases of growth (2- and 7-day-old cultures, respectively). The pilot study of acute toxicity, performed on C6 glioma cells, showed good tolerance of the drug up to 1000 micrograms/ml (4.8 x 10(-3) M), when cell growth slowed and a small part of the population was lethally damaged (8.3%, 20-h incubation interval). The changes became more extensive and appeared sooner (toward 5 h) at 2000 micrograms MHB/ml (9.5 x 10(-3) M). None of the four cell lines used was found to be affected in gross morphology or growth by 200 micrograms MHB/ml within a 5-day culture interval. When exposed to this dose for 4 h, the amount of 10B accumulated in cell lines at the exponential growth phase ranged from 0.51 to 4.4 ng/micrograms protein; in the stationary cultures of the corresponding cell phenotype, the 10B values were 3 to 10 times lower (0.12-1.2 ng/micrograms protein). Irrespective of the growth phase, the values achieved in C6 glioma cells were several times higher than in the other cell lines. Furthermore, in the glioma cells, particularly in the exponential phase of growth, accumulation of 10B proceeded against the marked concentration gradient. The data provide a new indication for the use of MHB for boron neutron capture therapy of brain tumors. PMID- 1501125 TI - Recovery of endothelium-dependent responses by reseeding endothelial cells in culture onto the denuded coronary artery. AB - Endothelium-denuded coronary artery was reseeded with the endothelial cells in culture, and the endothelium-dependent responses were compared with those in arteries with or without native endothelium. A23187 produced a relaxation in the arterial preparations reseeded with cultured endothelial cells in the cell suspension of 10(5) cells/ml for 17 to 19 hr, whereas no relaxation was observed in the denuded artery. Relaxing response to Ca++ ionophore A23187 was dependent on the number of endothelial cells reseeded. The A23187-induced relaxation in the cell-reseeded artery was inhibited markedly by pretreatment with 3 x 10(-4) M NG monomethyl-L-arginine or 5 x 10(-5) M methylene blue, but not 10(-4) M aspirin. NG-monomethyl-L-arginine (3 x 10(-4) M) and methylene blue (5 x 10(-5) M) produced a contraction in the cell-reseeded artery. Contraction evoked by bradykinin in the denuded arteries was attenuated by reseeding endothelial cells. KCl-induced contraction in the endothelium-reseeded artery did not differ from that in the denuded artery. Contractile responses to norepinephrine and serotonin were attenuated by reseeding endothelial cells onto the denuded artery to a small extent. Scanning electron microscopy showed that the luminal surface of endothelium-reseeded arteries was partly covered with endothelial cells. We conclude that when the cultured endothelial cells are reseeded onto a denuded coronary artery, endothelium-derived relaxing factor release occurs, but endothelium-dependent mechanisms are not the same as those for native cells. PMID- 1501126 TI - Effect of leukotriene D4 on gastric emptying and secretion in rhesus monkeys. AB - Gastric function was evaluated in conscious rhesus monkeys after an i.v. infusion of saline (0.11 ml/min) or leukotriene D4 (LTD4) (0.1 or 0.2 microgram/kg/min), a s.c. injection of nordihydroguaiaretic acid (4,4'-(2,3-dimethyl-1,4-butanediyl) bis[1,2-benzenediol]) (NDGA), a nonspecific lipoxygenase inhibitor, or an intragastric bolus of (1,1,1-trifluoro-N-[3-(2-quinolinylmethoxy)phenyl] methane sulfonamide) (Wy-48,252), a LTD4 receptor antagonist. Using a technesium diethylenetriamine-pentaacetic acid dilution technique, gastric emptying and secretion were determined in response to an 80-ml load of water. At the end of some studies, the animals were gastroscoped to obtain biopsies for histological evaluation. There were no differences in the microscopic appearance of the mucosa among the various groups. A continuous infusion of LTD4 significantly inhibited hydrogen and sodium ion secretion at doses that had no effect on systemic blood pressure or heart rate. In contrast, NDGA and Wy-48,252 had no effect on unstimulated (basal) fluid or ion secretion. Gastric emptying after the water load was unaltered by LTD4, but high doses of NDGA or Wy-48,252 decreased gastric emptying during the first 10 min. Thus, LTD4 does not appear to play a major role in gastric emptying or secretion in response to a water load, but may contribute to the changes in gastric function in response to potential gastric irritants. PMID- 1501127 TI - Fuscoside: an anti-inflammatory marine natural product which selectively inhibits 5-lipoxygenase. Part I: Physiological and biochemical studies in murine inflammatory models. AB - The biological and biochemical pharmacology of fuscoside, a novel anti inflammatory marine natural product isolated from the Caribbean gorgonian Eunicea fusca, has recently been characterized using murine (part I) and human (part II) models of inflammation. Topically applied fuscoside (FSD) effectively inhibits phorbol myristate acetate (PMA)-induced edema in mouse ears at levels comparable with indomethacin over a 3.3-hr exposure period, and is significantly more efficacious than indomethacin over 24 hr in the PMA model. Histological preparations and quantification of the neutrophil-specific marker, myeloperoxidase, demonstrate that FSD inhibits neutrophil infiltration into PMA induced regions of edema and inflammation. In systemic studies, where FSD is injected i.p. before the topical application of PMA, negligible effects on ear inflammation are observed. FSD does not inhibit bee venom or human synovial fluid phospholipase A2 up to concentrations of 500 microM. In calcium ionophore activated cultures of mouse peritoneal macrophages, FSD selectively and irreversibly inhibits leukotriene C4 biosynthesis (IC50 = 8 microM), yet has negligible effects on prostaglandin E2 production. FSD is also without effect on the conversion of arachidonic acid to prostaglandin E2 by ram seminal vesicle cyclooxygenase. Chromatographic and spectroscopic studies suggest that FSD is not metabolized, and that drug uptake/binding by macrophages is time dependent, saturable and independent of active transport mechanisms. These studies represent the first report of an anti-inflammatory marine natural product that selectively inhibits leukotriene biosynthesis. PMID- 1501128 TI - Sensory characteristics of monkey thalamic and motor cortex neurones. AB - 1. Extracellular single-cell recordings were made from the cerebellar thalamus, the ventro-posterior lateralis par caudalis (VPLc) and motor cortex of three conscious monkeys. Recordings were made from the thalamus as well as the cortex in two monkeys. In all, recordings were made from the thalamus in four hemispheres and from the motor cortex in four hemispheres. The animals were trained to permit a detailed examination when relaxed. Unexpected perturbations were applied to the wrist. Seventy-seven wrist-related neurones were recorded in the cerebellar thalamus, forty-two neurones from the VPLc and eighty-four neurones in motor cortex. 2. Cerebellar nuclear stimulation was used to physiologically identify thalamic neurones receiving input from the cerebellum. The location of all neurones was verified histologically. 3. The majority of cerebellar thalamic neurones had deep sensory receptive fields related to a single muscle, a group of synergists or a single joint. There was a distinct topographical organization. These fields were similar to sensory fields in motor cortical neurones, but had higher thresholds. 4. VPLc neurones had discrete deep or cutaneous sensory fields, or a combination of these fields, which suggests convergence. VPLc neurones had fields with lower thresholds than cerebellar thalamic neurones. The somatotopically located forelimb area in the VPLc was posterior to and continuous with the forelimb area in the cerebellar thalamus. 5. VPLc neurones responded with a shorter latency to wrist perturbations than did cerebellar thalamic neurones. VPLc neurones with deep sensory fields changed firing significantly earlier than those with cutaneous fields. The VPLc is likely to be the major source of sensory input to the motor cortex, and based on the results of this study we suggest that the VPLc is the thalamic nucleus best placed to transmit short-latency afferent input from the forelimb. 6. The timing of the neuronal discharge of cerebellar thalamic and VPLc cells, which resulted from perturbations of the wrist, was best linked to the duration of movement rather than its amplitude. The cells began firing as soon as the velocity changed sign and continued firing until the sign of the velocity changed again. In subsequent corrective movements neuronal discharge in the VPLc appeared to also encode movement acceleration. PMID- 1501129 TI - Impulses and resting membrane properties of small cultured rat hippocampal neurons. AB - 1. The impulses and resting membrane parameters of small (soma diameter less than 10 microM) cultured hippocampal neurons from rat embryos were studied with the tight-seal whole-cell recording technique. 2. Mean resting potential was -47 mV, mean input resistance 3.3 G omega, mean capacitance 11 pF, and mean time constant 33 ms. 3. Rectangular suprathreshold current steps elicited regenerative potential responses. The amplitude and time course of the responses were clearly stimulus dependent: stronger current steps caused impulses of larger amplitude. 4. The current threshold was very low: rheobase current was less than 15 pA. 5. The potential response depended on the preceding holding potential, responses from more negative potentials showing sharper peaks than those from more positive potentials. 6. Spontaneous impulses with pre-potentials similar to synaptically induced events were recorded from several cells. The amplitude of the spontaneous impulses varied similarly to that of the stimulus-induced responses. PMID- 1501130 TI - Membrane currents in small cultured rat hippocampal neurons: a voltage-clamp study. AB - 1. The currents underlying the graded impulses in small cultured hippocampal neurons from rat embryos were analysed under voltage-clamp conditions with the tight-seal whole-cell recording technique. 2. The leak and capacitative currents induced by a potential step were linearly related to the potential in the range studied (-60 to -100 mV). 3. With steps to potentials more positive than -40 mV, at least two different potential-activated currents were detected: an initial transient current and a delayed sustained one. In addition, 40% of the cells studied showed a delayed transient current. 4. The initial transient current showed sigmoid activation and roughly exponential inactivation. Its reversal potential depended on the Na+ concentration and was close to the Na+ equilibrium potential. Further, it was blocked by 3.0 microM-tetrodotoxin, and was abolished when choline was substituted for Na+ in the extracellular solution. We concluded that this current was carried mainly by Na+ ions. 5. The delayed sustained current showed sigmoid activation and almost no inactivation within 40 ms. The reversal potential was close to the K+ equilibrium potential. We concluded that this current was carried mainly by K+ ions. 6. The delayed transient current was outward in the potential range studied (-50 to +120 mV) and did not depend on the pipette Cl- concentration. It was assumed that this current was carried mainly by K+ ions. 7. A quantitative description of the initial transient and the delayed sustained currents was developed on the basis of earlier descriptions of excitable membranes. PMID- 1501131 TI - Computed potential responses of small cultured rat hippocampal neurons. AB - 1. The potential responses of small hippocampal neurons were computed on the basis of a previous mathematical description of the currents recorded under voltage-clamp conditions. 2. The computed action potentials were graded with respect to stimulus strength, in accordance with previous experimental findings. 3. The time course of the membrane currents and of the permeabilities and permeability variables during the impulse was computed for different stimulus intensities. 4. The effect of the membrane time constant on the impulse amplitude was investigated. It was concluded that the value of the time constant used was not per se sufficient to explain the amplitude variation of the impulse. 5. The effect of the magnitudes of the different potential-dependent permeabilities on the impulse amplitude was investigated. A Na+ permeability within a certain range caused impulses of variable amplitude, and this variability was affected by the K+ permeability. PMID- 1501132 TI - Role of protein kinase C in constrictor responses of the rat basilar artery in vivo. AB - 1. The goal of this study was to determine the effects of activation and inhibition of protein kinase C on the rat basilar artery in vivo. 2. The diameter of the basilar artery was measured through a craniotomy in rats anaesthetized with pentobarbitone sodium (50 mg kg-1, I.P., supplemented with 20 mg kg-1 h-1). Diameters were measured under control conditions and during topical application of various agonists, both alone and in the presence of antagonists. 3. Serotonin (5-HT) produced concentration-related constriction of the basilar artery (baseline diameter = 234 +/- 9 microns, mean +/- S.E.M.), which was inhibited by the 5-HT2 receptor antagonist LY53857. 4. Sphingosine (10(-6) M), a protein kinase C inhibitor which binds to the regulatory site of protein kinase C, inhibited the response to 10(-8) M-serotonin (-19 +/- 2% before vs. -3 +/- 2% during sphingosine, P less than 0.05). In contrast, constrictor responses to prostaglandin F2 alpha to (PGF2 alpha; 10(-6) M) were not inhibited by sphingosine (-16 +/- 2% before vs. -18 +/- 2% during sphingosine, P greater than 0.05). 5. H-7 (10(-9) M), another protein kinase C inhibitor, which binds to the catalytic site of protein kinase C, also inhibited constriction of the basilar artery in response to serotonin, but not prostaglandin F2 alpha. 6. Phorbol 12,13 dibutyrate (PDBu, 10(-8) M), which activates protein kinase C, produced slowly developing constriction of the basilar artery. PDBu-induced vasoconstriction (-33 +/- 2%) was attenuated by sphingosine (-11 +/- 4% during sphingosine, P less than 0.05) and H-7 (-1.5 +/- 5% during H-7, P less than 0.05). 7. In summary, activation of protein kinase C appears to mediate vasoconstrictor responses of the basilar artery to serotonin, but not PGF2 alpha. PMID- 1501133 TI - Spontaneous release of nitric oxide inhibits electrical, Ca2+ and mechanical transients in canine gastric smooth muscle. AB - 1. In canine antrum, rhythmic electrical activity consists of a rapid upstroke phase followed by a plateau depolarization. In response to slow waves, cytosolic Ca2+ ([Ca2+]cyt) and tension increased. 2. Addition of sodium nitroprusside (SNP, 0.5 microM) decreased the amplitude of the plateau phase of slow waves without significant effects on the upstroke depolarization. SNP also inhibited changes in [Ca2+]cyt and tension associated with the plateau potential. SNP induced a negative chronotropic effect at concentrations above 0.1 microM. 3. Similar to the effects of SNP, illumination of muscles during slow waves with ultraviolet (UV) light caused premature repolarization. UV illumination is known to release NO in some tissues. 4. L-NG-monomethyl-arginine (L-NMMA, 300 microM), Methylene Blue (MB, 5 microM) and oxyhaemoglobin (oxy-Hb, 5 microM) increased the force of contractions. In contrast, L-arginine (L-Arg, 300 microM) decreased contractile force and antagonized the effects of L-NMMA. 5. During the upstroke phase, SNP caused a small reduction in [Ca2+]cyt and a large reduction in force, suggesting that SNP caused a decrease in Ca2+ sensitivity. 6. In muscles permeabilized by alpha-toxin, cyclic GMP (100 microM) and UV illumination inhibited Ca(2+)-induced contraction (at pCa 5.5). 7. These data suggest that NO or NO-related compounds are spontaneously released in gastric muscles. These agents have two effects on excitation-contraction coupling: (i) inhibition (directly and/or indirectly) of the voltage-dependent Ca2+ channels that participate in the plateau phase of slow waves, and (ii) reduction in the Ca2+ sensitivity of the contractile element. PMID- 1501134 TI - The role of acetylcholinesterase in denervation supersensitivity in the frog cardiac ganglion. AB - 1. The sensitivity of normal and denervated cardiac ganglion cells to the cholinergic agonists acetylcholine and carbamylcholine (carbachol) were compared in the frog, Rana pipiens. Acetylcholine and carbachol bind to the same acetylcholine receptors, but, unlike acetylcholine, carbachol is resistant to hydrolysis by acetylcholinesterase. 2. Sensitivity was assessed by the peak depolarization elicited in response to a sustained pulse of ligand emitted from a pipette positioned 10 microns from the ganglion cell surface. This technique allows the sensitivity of the entire cell to be recorded with a single measurement. 3. The acetylcholine sensitivity of normal cardiac ganglion cells was increased by inhibiting extracellular acetylcholinesterase with echothiophate. 4. Denervation increased the sensitivity of cardiac ganglion cells to acetylcholine but not to carbachol. 5. Following the inhibition of extracellular acetylcholinesterase with echothiophate, sensitivity to acetylcholine was similar in normal and in denervated ganglion cells. 6. The increased sensitivity to acetylcholine of cardiac ganglion cells following denervation is caused by a reduction in the hydrolysis of the transmitter by acetylcholinesterase rather than by changes in the number and/or properties of acetylcholine receptors. PMID- 1501135 TI - The activity of monkey thalamic and motor cortical neurones in a skilled, ballistic movement. AB - 1. Three monkeys were trained to perform a reaction-time task of the wrist and single-cell recordings were made from the motor cortex (eighty-four cells), ventro-posterior lateralis par caudalis (VPLc) (forty-two cells) and cerebellar thalamus (seventy-seven cells). 2. The majority (43/77, 56%) of cerebellar thalamic neurones fired phasically during movement, whereas in the motor cortex most neurones (53/84, 64%) had a phasic-tonic discharge pattern. Most neurones in both locations discharged in relation to the direction of movement (reciprocal pattern). 3. The cerebellar thalamus is unlike the motor cortex in that it does not usually encode a signal for force or joint position in its discharge. 4. Twenty-two per cent (17/77) of cerebellar thalamic neurones had a period of reduced discharge rate before the phasic burst of activity, and represent a pattern of discharge not seen in motor cortex or VPLc neurones. 5. The onset of phasic activity in the cerebellar thalamus was significantly later (average 94 ms) than in the motor cortex but occurred just before electromyogram (EMG) activity. The phasic activity in the cerebellar thalamus usually ended before the phasic component of motor cortex discharge was completed. 6. Phasic activity in VPLc neurones commenced after the onset of EMG discharge and on average 26 ms after the commencement of movement. Most neurones with deep sensory receptive fields fired with a reciprocal pattern, while neurones with cutaneous fields usually fixed bidirectionally in relation to the task. Almost one-third of neurones signalled force and a similar number had discharge levels that encoded characteristics of the joint position. 7. The duration of discharge of VPLc neurones during the voluntary movement was marginally less than the duration of the movement velocity peak and the VPLc may therefore be signalling the duration of the velocity. Phasic activity in cerebellar thalamic neurones fired for a duration similar to the VPLc neurones, but commenced before the movement. Therefore, if the cerebellar thalamus is carrying information about the duration of the velocity, it does so before the movement starts. 8. The phasic burst of activity in cells of the cerebellar thalamus is timed so that it can contribute to the later component of the phasic burst of motor cortical discharge. Thus we speculate that in skilled, ballistic movements, the cerebellum may provide a response which travels via the cerebellar thalamus and helps to determine the magnitude and duration of the phasic part of cortical discharge.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1501136 TI - Evidence that action potentials activate an internodal potassium conductance in lizard myelinated axons. AB - 1. We have studied action potentials and after-potentials evoked in the internodal region of visualized lizard intramuscular nerve fibres by stimulation of the proximal nerve trunk. Voltage recordings were obtained using microelectrodes inserted into the axon (intra-axonal) or into the layers of myelin (peri-internodal), with the goal of studying conditions required to activate internodal K+ currents. 2. Peri-internodal recordings made using K2SO4-, KCl- or NaCl-filled electrodes exhibited a negligible resting potential (less than 2 mV), but showed action potentials with peak amplitudes of up to 78 mV and a duration less than or equal to that of the intra-axonally recorded action potential. 3. Following ionophoretic application of potassium from a peri internodal microelectrode, the peri-internodal action potential was followed by a prolonged (hundreds of milliseconds) negative plateau. This plateau was not seen following peri-internodal ionophoresis of sodium. The prolonged negative potential (PNP) was confined to the K(+)-injected internode: it could be recorded by a second peri-internodal microelectrode inserted into the same internode, but not into an adjacent internode. 4. The peri-internodally recorded PNP was accompanied by an equally prolonged intra-axonal depolarizing after-potential, and by an increase in the conductance of the internodal axolemma. However, the K+ ionophoresis that produced the PNP had little or no detectable effect on the intra-axonally or peri-internodally recorded resting potential or action potential. These findings suggest that the PNP is generated by an inward current across the axolemma of the K(+)-injected internode, through channels opened following the action potential. 5. Following peri-internodal K+ ionophoresis a PNP could also be evoked by passage of depolarizing current pulses through an intra-axonal electrode or by passage of negative current pulses through an electrode in the K(+)-filled peri-internodal region. The threshold for evoking a PNP was less than the threshold for evoking an action potential, and the PNP persisted in 10 microM-tetrodotoxin. Thus the PNP is evoked by depolarization of the axolemma rather than by Na+ influx. 6. The PNP was reversibly blocked by tetraethylammonium (TEA, 2-10 mM), but was not blocked by 100 microM-3,4 diaminopyridine or 5 mM-4-aminopyridine.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1501137 TI - The field adaptation of the human rod visual system. AB - 1. Incremental thresholds were measured in a retinal region 12 deg temporal from the fovea with a target of 200 ms in duration and 6 deg in diameter superimposed on background fields of various intensities and wavelengths. Measurements were made under rod-isolation conditions in five normal observers and in a typical, complete achromat observer who had no cone function. 2. The rise in threshold with background intensity changes with background wavelength in the normal trichromat observers. On 450, 520 and 560 nm backgrounds the average slope in logarithmic co-ordinates (0.78 +/- 0.04, S.D.) is similar to that found for the achromat--whose slope is independent of background wavelength (0.79 +/- 0.03)- but on a 640 nm background it more nearly approaches Weber's law (0.91 +/- 0.02). This indicates that the sensitivity of the rods to an incremental target is not determined by quantal absorptions in the rods alone but by quantal absorptions in both the rods and the cones. 3. Rod incremental thresholds were also measured in various colour-blind observers lacking one or more of the cone classes: a blue cone monochromat, four deuteranopes and a protanope. For the blue-cone monochromat, like the achromat, the slope of the increment threshold curve is constant with background wavelength. For the deuteranopes and the protanope, like the normal, the slope increases with wavelength. The protanope, however, shows a smaller increase in slope, consistent with the lower sensitivity of his cones to long-wavelength light. 4. The dependence of the field adaptation of the rods on the cones was confirmed by field-mixture experiments, in which the incremental threshold was measured against bichromatic backgrounds, and in silent substitution experiments, in which backgrounds equated for their effects on either the cones or the rods but not both were instantaneously substituted for one another. PMID- 1501138 TI - Depolarization of Ib afferent axons in the cat spinal cord during homonymous muscle contraction. AB - 1. Intra-axonal records from the intraspinal course of Ib and Ia afferent fibres innervating the gastrocnemius medialis muscle were obtained in chloralose or Nembutal-anaesthetized cats during submaximal contractions of the muscle. 2. Afferent fibres in continuity with their muscle of origin were functionally identified by their responses to muscle stretch or contraction. 3. In six out of eight Ib afferents, primary depolarizations (PADs) were recorded during contraction. They were independent of the presence of orthodromic impulses fired by tendon organs. 4. These observations support the assumption that the reduction of Ib autogenetic inhibition in homonymous and synergic motoneurones during GM contractions is due to presynaptic inhibition of transmission in Ib pathways. PMID- 1501139 TI - Hyperpolarization as a mechanism for endothelium-dependent relaxations in the porcine coronary artery. AB - 1. The nature of endothelium-dependent relaxations resistant to nitro-L-arginine was investigated in porcine coronary arteries by measuring isometric force and membrane potential in the presence of indomethacin. 2. Bradykinin induced concentration- and endothelium-dependent relaxations and hyperpolarization in tissues contracted with prostaglandin F2 alpha. Nitro-L-arginine did not affect either the relaxations or the hyperpolarization induced by bradykinin. The threshold concentration of bradykinin was the same for the nitro-L-arginine resistant relaxations and the membrane hyperpolarization. 3. Nitro-L-arginine resistant relaxations were evoked by several agents (A23187, thrombin and UK 14304) in addition to bradykinin. The amplitude of membrane hyperpolarizations observed with all agents was proportional to that of nitro-L-arginine-resistant relaxations. 4. Thrombin caused more transient relaxations and hyperpolarizations than bradykinin in the presence of nitro-L-arginine. 5. In tissues contracted with high K+ or tetrabutylammonium (a non-selective K(+)-channel blocker), bradykinin inhibited the contractions in a concentration-dependent manner, whereas membrane hyperpolarization was not observed. The relaxations evoked by the kinin were abolished by nitro-L-arginine. 6. These results suggest that endothelium-dependent relaxations which are resistant to nitro-L-arginine are mediated by membrane hyperpolarization in the porcine coronary artery. PMID- 1501140 TI - Synaptic behaviour in the myenteric plexus of the guinea-pig gastric antrum. AB - 1. Intracellular recording methods were used to study the synaptic behaviour of neurones in the myenteric plexus of the guinea-pig gastric antrum. Synaptic potentials occurred spontaneously or were evoked by focal electrical stimulation of interganglionic fibre tracts. Synaptic events consisted of fast and slow excitatory postsynaptic potentials (EPSPs) and inhibitory postsynaptic potentials (IPSPs). 2. Fast EPSPs with durations less than 20 ms were evoked in every antral neurone in a population sample of 370 cells. Most of the ganglion cells received multiple inputs from axons entering the individual ganglia in several different interganglionic fibre tracts. Many of the neurones also received input from multiple axons projecting in individual fibre tracts. The fast EPSPs behaved like nicotinic cholinergic EPSPs. They were evoked at stimulus frequencies up to 60 Hz without evidence of the run-down characteristic of fast EPSPs in the intestine. 3. Slow EPSPs were evoked by repetitive stimulation of the interganglionic connectives. They consisted of a slowly activating depolarization which persisted for several seconds after termination of the stimulus. The depolarizing responses were associated with an increase in the input resistance, with enhanced excitability and with suppression of hyperpolarizing after-potentials in AH/type 2 neurones. They were observed in 14.4% of the neurones of which 89% were AH/type 2 neurones. AH/type 2 neurones, unlike other myenteric neurones, were identified by action potentials with long lasting after-hyperpolarization. 4. IPSPs were hyperpolarizing potentials evoked by repetitive stimulation of interganglionic fibre tracts. The hyperpolarizing responses were associated with decreased input resistance. They occurred in 1.4% of the antral neurones. 5. Application of acetylcholine (ACh) by micro-ejection mimicked the fast EPSPs in all neurones. This fast nicotinic response to ACh was followed by a slowly activating, long lasting muscarinic depolarization in 32% of the neurones. The slow muscarinic response was associated with increased input resistance, suppression of hyperpolarizing after-potentials and enhanced excitability. 6. Fast EPSPs were not suppressed by accumulation of ACh at presynaptic transmitter release sites. Unlike the intestine, presynaptic muscarinic autoreceptors appeared to be absent from the microcircuits in the antrum. 7. Synaptic behaviour in the local circuits of the gastric antrum differed from the gastric corpus. This may be a reflection of specialization of the circuits for organization of the distinctive patterns of digestive behaviour found in this region of the stomach. PMID- 1501141 TI - Slow and fast transient potassium currents in cultured rat hippocampal cells. AB - 1. Potassium currents have been recorded from rat hippocampal neurons in dissociated cultures prepared at E17-E19. Currents were studied with the whole cell version of the patch clamp method. The kinetics and pharmacological properties of two transient outward currents have been characterized. 2. Most of the recordings have been done in cells which had been in culture 10-18 days. Both a fast and a slow transient current could be elicited. A subtraction procedure was used to isolate the fast transient current. The fast transient current decayed monoexponentially with a time constant of about 10 ms. The slow transient current decayed with two time constants in the order of 500 ms and of 3.4 s. The reversal potential of the slow current shifted by 54 mV for a tenfold change in extracellular potassium concentration. 3. Studies on the removal of inactivation for the two currents revealed time constants of 29 and 107 ms for the fast and slow transient current, respectively. 4. The steady-state inactivation properties of the fast transient current were determined by studying the current with a fixed depolarizing command of -10 mV and varying pre-pulse amplitudes from a holding potential of -50 mV. The inactivation curve could be fitted with a Boltzmann equation. Half-maximal inactivation occurred at -81 mV. The steady state activation properties of the fast transient current were determined by varying the depolarizing voltage commands following a fixed pre-pulse to -110 mV. The threshold for activation was between -70 and -60 mV. Half-maximal activation was reached at -19 mV. 5. The steady-state inactivation properties of the slow transient current were determined by studying the current elicited by varying the hyperpolarizing voltage steps from a holding potential of 0 mV. The inactivation curve could be fitted with a Boltzmann equation. Half-maximal inactivation was obtained at -61 mV. The steady-state activation properties were determined in a manner similar to the fast current. The threshold for activation was between -40 and -30 mV. 6. The slow transient current was not inactivated immediately when the conditioning pre-pulse was stopped. The rate of current decay increased with stimulus frequency. 7. Both transient currents were sensitive to 4-aminopyridine (4-AP). The fast transient current was blocked completely by 5 mM provided a pre pulse of 1 s to -110 mV was employed. The slow transient current was already depressed by 4-AP applied in the 100 microM range but could never be blocked completely.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1501142 TI - The importance of competition between motoneurones in developing rat muscle; effects of partial denervation at birth. AB - 1. The number of motor units in developing fourth deep lumbrical muscles was reduced by unilateral partial denervation of the muscle at birth, by cutting the lateral plantar nerve. A minority of the motor axons arrive via the sural nerve, and were thus not cut. Those muscles that contained one motor unit (one-unit muscles) after partial denervation developed in the absence of competition between motoneurones. Muscles with two motor units had little competition. A few four-unit muscles were studied for comparison. 2. Isometric twitch and tetanic tensions of single motor units were recorded in vitro at 60 days of age in response to stimulation of the sural nerve. On average, units in partially denervated muscles generated more tension than normal units. The isometric tension characteristics of the units in the one-unit and two-unit muscles were different from the normal units (e.g. slower contracting and more fatiguable). The units of four-unit muscles had properties similar to those of normal muscles. 3. Fibres of an individual unit were identified by glycogen depletion and S (slow) fibres were identified in cross-section that bound a polyclonal antibody to slow type I myosin. Those fibres that did not bind the antibody were designated F fibres. The units of one-unit muscles had the same total number of fibres and fibre type composition (both S and F fibres in the same unit) as estimated from previous work to exist at birth. The units of two-unit muscles contained the same total number of fibres, but apparently fewer S fibres, though this may have been as a result of incomplete glycogen depletion of some fibres. 4. It is concluded that competition between motoneurone terminals is necessary for the withdrawal of mismatched connections on muscle fibres present at birth; or, alternatively, that such withdrawal cannot take place if it would result in denervation of the muscle fibre. PMID- 1501143 TI - Plasma proteins modify the endothelial cell glycocalyx of frog mesenteric microvessels. AB - 1. We have investigated the interaction of plasma proteins with the endothelial cell using cationized ferritin as a marker of the cell surface glycocalyx. 2. Single microvessels of the frog mesentery were sequentially perfused using glass micropipettes with solutions containing cationized ferritin (CF, 6.7 mg ml-1) in 0.10 M-NaCl and then with either frog plasma or bovine serum albumin (BSA; 50 or 10 mg ml-1), or protein-free Ringer solution, before suffusion fixation in 2.5% glutaraldehyde. 3. A layer of CF, usually two to four molecules thick, was associated with the luminal endothelial cell surface. In vessels post-flushed with protein-free Ringer solution the CF layer was closely adherent to all regions of the luminal endothelium, including the plasma membrane, vesicle diaphragms, coated pits and the entrances to clefts. However, when plasma was present during fixation the CF layer was separated from the cell surface by up to 100 nm over all regions. In vessels post-flushed with BSA the CF layer was also separated from the membrane but the effect was less striking. 4. The association of cationized ferritin with the endothelial cell surface was assessed quantitatively using electron micrographs of transverse sections (approximately 50 nm thick) of the perfused vessels, and expressed in terms of the depth of the layer of CF associated with the endothelial cell surface, its separation from the plasma membrane of the luminal endothelium, and the concentration of CF in the layer. The mean (+/- S.D.) separation in the presence of plasma, 32.3 +/- 10.5 nm (n = 12), was significantly greater (P less than 0.01) than that with either protein-free Ringer solution, 3.0 +/- 1.4 nm (n = 9), or BSA in Ringer solution, 8.3 +/- 3.0 nm (n = 8). The separation seen with BSA in Ringer was also significantly greater than that measured with a final Ringer solution perfusion (P less than 0.01). The effects of 10 and 50 mg ml-1 BSA were not different from one another. The total glycocalyx thickness, defined as the sum of the separation layer and depth of CF layer, with plasma present, 56.2 +/- 13.7 nm, was twice the value seen with Ringer solution, 28.0 +/- 9.1 nm (P less than 0.01), while the total thickness with BSA, 30.9 +/- 5.4 nm, was not different from the Ringer solution value.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1501144 TI - A frequency analysis of neuronal activity in monkey thalamus, motor cortex and electromyograms in wrist oscillations. AB - 1. Extracellular recordings were made in three monkeys while recording from neurones in the motor cortex (eighty-four cells), ventro-posterior lateralis pars caudalis (VPLc, forty-two cells) and cerebellar thalamus (seventy-seven cells). 2. This experiment was designed to produce active and reflex movements of varying velocities in order to study the relationship between amplitude of velocity and magnitude of neuronal discharge of thalamic neurones. The active movements were voluntary rapid alternating movements (RAMs) of the wrist and the reflex movements were produced by forcibly oscillating the wrist joint between frequencies of 1 and 7 Hz (forced oscillations). 3. This study was also designed to examine cerebellar influences on a reflex path, namely the transcortical reflex loop. Forced oscillations were predicted to provide circumstances where active damping was required to prevent excessive oscillations in the reflex path. Rapid alternating movements of the wrist were predicted to provide circumstances where oscillations at the natural frequency in that reflex path would support and propagate the movements. 4. Forced oscillations from 1 to 7 Hz produced movements of different velocities. VPLc and cerebellar thalamic neurones discharged in relation to the duration of movement in a particular direction, but their discharge levels were unrelated to the magnitude of the velocity. Motor cortex neurones fired in a pattern which was related to the timing but not the magnitude of the acceleration. 5. In forced oscillations of the wrist the resonant frequency was between 3 and 7 Hz. They may be controlled in part by a transcortical reflex. The cerebellar thalamic neurones did not fire before motor cortex neurones. Therefore, it is unlikely that the cerebello-thalamo-cortical pathway is necessary to damp these potentially unstable oscillations by an effect on antagonist-related cortical neurones. 6. Rapid alternating movements (RAMs) of monkeys' wrists were performed in a stereotyped fashion over a narrow range of frequencies with the greatest displacement in joint angle and peak velocity at the natural frequency of 3-5 Hz. 7. During the performance of RAMs, neuronal discharge modulated sinusoidally in the VPLc, cerebellar thalamus and motor cortex. There was no relationship between velocity and neuronal discharge of the cerebellar thalamic and motor cortical neurones but there did appear to be a relationship between velocity and VPLc neuronal discharge. 8. The onset of electromyogram (EMG) discharge changed earlier than neuronal discharge in the motor cortex and thalamus during the performance of RAMs.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1501145 TI - The effect of intracellular pH on ATP-dependent potassium channels of frog skeletal muscle. AB - 1. We have used patch-clamp methods to study the effects of pH at the cytoplasmic surface of the membrane on ATP-dependent K+ channels (KATP channels) in patches excised from frog (Rana temporaria) skeletal muscle, and to study the kinetics of ATP binding. 2. In the absence of ATP, a reduction in pH led to a slight decrease in single-channel current amplitude, an increase in the number of very brief closings, an increase in the apparent mean open time, and an increase in burst duration. After correction for missed closings, the change in mean open time was slight. Despite these changes in detailed kinetics, the channel open-state probability, Popen, changed little with changes in pH in the absence of ATP. 3. In the presence of ATP, a decrease in internal pH (pHi) reduced the degree of channel inhibition by ATP, shifting the curve relating Popen and [ATP] to higher concentrations of ATP without altering its steepness. The ATP concentration for half-inhibition of channel activity (Ki) was 17 microM at pH 7.2 and 260 microM at pH 6.3. 4. The effect of pH could be modelled by assuming that one or two protons bind to the channel and prevent ATP binding to exert its effect of causing channel closure. The predicted dissociation constants for ATP and H+ respectively were 5.4 and 0.11 microM. 5. The rate constants for binding and unbinding of ATP were estimated from the dependence of the mean open time on [ATP] and from the Ki. The apparent rate constants for ATP binding were 0.6 and 0.04 mM-1 ms-1 at pH 7.2 and 6.3 respectively, while the rate constant for unbinding was 0.01 ms-1. In terms of our model the calculated true rate constant for ATP binding was 1.85 mM-1 ms-1. ATP binding also led to a reduction in burst duration. 6. The effect of pH described here differs from findings in cardiac muscle and pancreatic B-cells. The results are discussed in relation to the possible function of KATP channels in skeletal muscle during exercise. PMID- 1501146 TI - Mechanisms by which the pregnant ewe can sustain increased salt and water supply to the fetus. AB - 1. Nine chronically catheterized pregnant ewes were monitored before, during and after 1 week in which fetal urine was drained continuously, to determine whether they could compensate for the resulting loss of salt and water and increase net supply across the placenta to the fetus. 2. Fetal growth and urine and lung liquid production were not affected by loss of all fetal fluids. 3. When fetal urine was drained, the increase (P less than 0.05) in maternal drinking was greater than the extra amount of fluid lost. Thus, maternal plasma osmolality fell (P less than 0.01). When fetal urine again flowed into the amniotic and allantoic cavities, maternal drinking did not fall significantly and plasma osmolality remained low. Maternal urine flow rate increased (P less than 0.05) and its osmolality fell (P less than 0.02). 4. Maternal food intake increased (P less than 0.005) during fetal urine drainage. 5. Maternal plasma renin activity increased (P less than 0.05), her urinary sodium excretion fell (P less than 0.005) and the Na(+)-K+ ratio in both her urine and faeces decreased (P less than 0.01 and P less than 0.05 respectively) when fetal urine was drained. Maternal urinary and faecal sodium conservation continued after drainage ceased because of continued loss of sodium in lung liquid. 6. It is concluded that the ewe can compensate for inappropriate loss of salt and water from the conceptus. PMID- 1501147 TI - Parvalbumin, labile heat and slowing of relaxation in mouse soleus and extensor digitorum longus muscles. AB - 1. Parvalbumin content, heat rate and rate of relaxation were measured in two mouse muscles: the slow-twitch soleus and the fast-twitch extensor digitorum longus (EDL). 2. No trace of parvalbumin was found in the soleus; EDL contained a mean of 4.86 mg of this protein per gram of fresh muscle (S.D. = 1.25). 3. Heat rate during 7 s isometric tetani in isolated soleus muscle at 20 degrees C can be described by the sum of an exponentially decaying term and a constant term. The exponential term is reduced by 67% in a second tetanus performed 1 s after a first one; its repriming is complete after a resting period of about 1 min. The exponential term has therefore the properties of labile heat. 4. Relaxation rate measured during 15 s of isometric interrupted tetani at 20 degrees C is nearly constant in the soleus, but decreases continuously with increasing tetanus duration in the EDL. In the latter, isometric tension also decreases continuously. 5. Therefore, parvalbumin can account neither for the labile heat production in mouse soleus nor for the slowing of relaxation associated with muscle fatigue observed after a few seconds of tetanus in EDL. The role of parvalbumin in striated muscles is thus reassessed, and other possible causes of labile heat production and slowing of relaxation are discussed. PMID- 1501148 TI - Pursuit of intermittently illuminated moving targets in the human. AB - 1. Experiments have been conducted in order to establish the changes in oculomotor activity which take place when the human subject attempts to pursue an intermittently illuminated moving target. 2. In an initial experiment, target motion in the horizontal plane was composed of one or two sinusoids at frequencies between 0.11 and 0.2 Hz. The target was illuminated for varying durations (10-320 ms) at intervals between 40 and 960 ms. As pulse interval was increased or pulse duration was decreased there was a progressive increase in eye velocity gain for the smooth component of eye movement. Some smooth eye movement was generated even when the pulse interval was as large as 960 ms. 3. In a second experiment target motion consisted of a triangular waveform in which target presentation was timed to occur at regular intervals throughout each cycle. Overlaying and averaging the response from several cycles revealed a regular pattern of pulsatile activity associated with each target presentation. This response, which was particularly evident when the pulse interval was greater than 1 s, consisted of an initial build-up of smooth eye velocity followed by an exponential decay with a time constant of 0.5-2 s. When the pulse interval was less than 1 s there was a summation of the transient responses so that eye movement appeared quite smooth when pulse interval was reduced to 320 ms. 4. The pulsatile nature of the response was accentuated when the target was made to execute a staircase-ramp waveform in which the target was illuminated only during the ramp component. The elimination of position change between ramps and the ability to achieve higher target velocity led to clear evidence of the summation of transient oculomotor responses. 5. The summated effects, however, were not simply attributable to the addition of responses to individual target presentations as indicated by the timing of each response. The eye velocity pulse was frequently initiated 200-300 ms prior to target appearance, and well before the time (100 ms) at which visual feedback would be expected to become effective. 6. The effect of target step displacement alone was investigated by examination of the smooth eye movement initiated by varying numbers of steps in the waveform. This showed that the basic step response had a peak velocity of no more than 8-10 deg/s in most individuals.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1501149 TI - Tension transients during steady lengthening of tetanized muscle fibres of the frog. AB - 1. Steady lengthenings at different velocities (0.02-1.6 microns/s per half sarcomere, temperature 2.5-5.5 degrees C) were imposed on isolated frog muscle fibres at the plateau of the isometric tetanus (tension T0). When tension during lengthening had attained a steady value (Ti), which varied from about 1.5 to about 2 times T0 depending on lengthening velocity, tension transients were elicited by applying step length changes of different amplitudes. The change in length of a selected segment, close to the end of the fibre connected to the force transducer, was controlled by means of a striation follower. 2. The instantaneous plots of tension versus the length change during the step itself showed that at the high forces developed during steady lengthening, as at the plateau of isometric tetanus, the elasticity of the fibre was almost undamped in the whole range of lengthening velocities used. 3. The tension transient elicited by step length changes imposed in isometric conditions exhibited the characteristic four phases described previously: following the tension change simultaneous with the step (phase 1), there was a quick partial recovery (phase 2, the speed of which increased going from the largest step stretch to the largest step release), a subsequent pause or inversion in recovery (phase 3) and finally a slower approach to the tension before the step (phase 4). 4. In the region of small steps the plot of the extreme tension attained during the step (T1) versus step amplitude appeared more linear during steady lengthening than in isometric conditions and deviated progressively from linearity with increase in the size of step releases. The amount of instantaneous shortening necessary to drop tension to zero (Y0), measured by the abscissa intercept of the straight line drawn through T1 points for small steps, was about 4.1 nm per half-sarcomere in isometric conditions and 5.4 nm per half-sarcomere during lengthening at low speed (0.09 microns/s per half-sarcomere, Ti about 1.6 T0). Taken altogether this indicates, in agreement with previous work, that force enhancement during steady lengthening is due to increase in both number and extension of attached cross bridges. During lengthening at high speed (0.8 microns/s per half-sarcomere), further enhancement in steady force (Ti about 1.9 T0) was accompanied by increase of Y0 to 6.3 nm per half-sarcomere, indicating that increase in lengthening velocity exclusively produces increase in cross-bridge extension.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1501150 TI - Effects of amino acids on zinc transport in rat erythrocytes. AB - 1. A significant proportion of plasma zinc exists complexed with amino acids. The effect of amino acids on the accumulation of radioactive zinc by rat erythrocytes was studied in vitro, to investigate the hypothesis that zinc might be transported into cells as an amino acid-zinc complex. 2. L-Histidine (500 microM 10 mM) stimulated 65Zn uptake; 50 mM-L-histidine gave a slight inhibition of uptake. D-Histidine (500 microM-10 mM) inhibited uptake in a dose-dependent manner. A non-zinc-binding amino acid, L-alanine, did not affect 65Zn uptake. 3. The effect of L-histidine was sodium dependent and temperature dependent, but was DIDS insensitive. These properties suggest that zinc is being transported as a zinc-histidine complex, utilizing an amino acid carrier system. Uptake of zinc in the presence of L-histidine differed from the previously described ionic mechanism, and may represent a physiological route of uptake. 4. L-Histidine stimulated efflux of 65Zn from pre-loaded cells. 5. The relevance of transport of a zinc-histidine complex is discussed with reference to histidinaemia, and as a significant zinc transport system in the presence of the very low ionic zinc concentrations found in plasma. PMID- 1501151 TI - Fetal breathing, sleep state and cardiovascular adaptations to anaemia in sheep. AB - 1. In unanaesthetized fetal sheep (greater than 0.8 term) prolonged anaemia initially reduced the incidences of low-voltage electrocortical activity, rapid eye movements and breathing activity; but the incidence of each returned to normal within 4-7 h. 2. Anaemia induced a persistent rise in fetal heart rate and plasma concentrations of adrenaline, noradrenaline and cortisol. 3. After 16 h the fetal haematocrit was returned to normal. Isocapnic hypoxia induced less than 1 h later also inhibited eye and breathing activity. 4. After 1 h fetal arterial PO2 (Pa,O2) was returned to normal. This rise in O2 tension was associated with an elevation in the incidence of low-voltage electrocortical activity, eye movements and breathing. Breathing movements also occurred during high-voltage electrocortical activity. 5. It is concluded that the brain PO2 set-point for hypoxic inhibition adapts rapidly to alterations in O2-carrying capacity and is probably due to changes in the concentration and/or receptor affinity of a central neuromodulator. Secondly, a rise in brain PO2 at birth may contribute to the onset of continuous breathing. PMID- 1501153 TI - Effects of 2-amino-4-phosphonobutyric acid on cells in the distal layers of the tiger salamander's retina. AB - 1. We studied the effects of 2-amino-4-phosphonobutyric acid (APB) on the response properties of rods, horizontal cells and bipolar cells in the isolated, perfused retina of the tiger salamander, Ambystoma tigrinum. A concentration of 100 microM was found to be sufficient to elicit maximal effects. 2. Rods hyperpolarized slightly upon exposure to 100 microM-APB and their response amplitudes were slightly reduced. The amplitude of the cone-generated component of the rod's response to 700 nm light was not significantly affected by APB. 3. Horizontal cells hyperpolarized by 2-5 mV upon exposure to 100 microM-APB. The rod-driven component of the horizontal cell response increased in amplitude while the cone-driven component decreased in amplitude. APB thus causes an increase in voltage gain between rods and horizontal cells and a decrease in cone/horizontal cell gain. These findings can be explained in terms of an APB-induced reduction in transmitter release from the cones. 4. APB at a concentration of 100 microM caused an increase in the length constant of the horizontal cell syncytium. Our analysis shows this to be due primarily to a 50% reduction in the coupling impedance between the cells of the syncytium. 5. The effects of APB on off-centre bipolar cells were qualitatively similar to those on horizontal cells. APB increased the amplitudes of rod-driven responses and reduced those of cone-driven responses. The length constants, both of the receptive field centre and of the surround, were increased and the strength of the surround relative to the centre was reduced by about 20%. 6. APB abolished the depolarizing light responses of the receptive field centres of on-centre bipolar cells. A hyperpolarizing response remained whose spatial properties were similar to those of the receptive field surround. We believe this response to reflect a direct (feedforward) input to on-centre bipolar cells from horizontal cells. PMID- 1501152 TI - The source of calcium for muscarinic-mediated catecholamine release from cat adrenals. AB - 1. In view of conflicting reports on the source of Ca2+ needed to trigger the secretory response to muscarinic stimulation of chromaffin cells, we have reinvestigated this problem in the cat adrenal gland perfused with oxygenated Krebs solution at 37 degrees C. Above a basal rate of secretion of 60 ng/30 s of total catecholamines, 5 s pulses of 100 microM-methacholine evoked 10-fold increases of secretion. This response was entirely mediated by muscarinic receptors, since it was blocked by submicromolar concentrations of atropine but not by d-tubocurarine. 2. Delayed application of methacholine pulses after Ca2+ removal from the Krebs solution led to a progressive decline of the secretory response with a t1/2 of 15 s. Secretion was blocked by 85% after a 60 s period of Ca2+ deprivation; extension of the external Ca2+ (Ca2+o) wash-out period up to 5 min did not further reduce the secretory response. 3. When EGTA (1 mM) was present in the 0 Ca2+ solution, the rate of decline of methacholine responses, as a function of the time of exposure to 1 mM-EGTA, was similar to that obtained with 0 Ca2+. Again, about 15-20% of the secretory response was resistant even to prolonged periods of washing out with the 0 Ca(2+)-EGTA solution. 4. The Ca2+ ionophore ionomycin (1 microM) first decreased and then accelerated the rate of decline of methacholine responses upon Ca2+o wash-out. Particularly relevant is the complete blockade of secretion when the Ca2+o wash-out is performed in the presence of this ionophore. This suggests the existence of a small intracellular functional Ca2+ store sensitive to ionomycin. 5. After abolition of the secretory response through 60 s periods of wash-out with a 0 Ca(2+)-EGTA-ionomycin solution, followed by delayed 5 s methacholine pulses after Ca2+o reintroduction, the glands instantly recovered their normal muscarinic-mediated secretory response. This suggests that upon muscarinic stimulation, Ca2+ required by the secretory machinery to trigger such response immediately comes from extracellular sources. How Ca2+o gains the cell interior so fast upon muscarinic stimulation is unknown; we have previously suggested that the muscarinic receptor in the cat chromaffin cell could be coupled to an ionophore channel which might be chemically activated by muscarinic agonists. 6. Secretory responses to 5 s pulses with 35 or 100 mM-K+ declined faster (t1/2 of 3 and 6 s, respectively) upon Ca2+o wash-out than those of methacholine.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1501154 TI - Prevalence of developmental enamel defects in children with cerebral palsy. AB - Enamel defects observed in primary anterior teeth of 123 children with congenital cerebral palsy (CP) born 1983 through 1985 in four northern California counties were categorized using an adaptation of the Developmental Defects of Enamel Index. Nineteen children (15%) had crowns or loss of tooth substance (LTS) due to attrition. Missing enamel (ME) including horizontal groove, was observed in 39 children (32%). Twenty-four children without ME (20%) had enamel pits, vertical grooves, or colored enamel opacities. Forty-one (33%) had clinically normal enamel. ME children did not differ significantly from those with normal enamel with respect to race, sex, singleton vs twin, severity or type of CP, or presence of dysmorphic features. ME children more often had shorter gestational ages than children with normal enamel. More ME children, even those who were not low in birth weight, were reported by parents to have required neonatal intensive care. PMID- 1501155 TI - The lateral periodontal cyst: an update. AB - Lateral periodontal cysts account for 0.8% of all jaw cysts seen in our department. Published reports have indicated that they occur most frequently in the 5th to 7th decades, that there is a male preponderance and that they are located mainly in the mandibular canine-premolar region. In our own series of 20 cases, 10 were found in the anterior maxilla. We have distinguished unicystic and multicystic (including botryoid) varieties. They were lined predominantly or exclusively by thin reduced enamel epithelium-like tissue which contained many clear cells and epithelial thickenings referred to as plaques. Glycogen was present in the epithelium of two-thirds of our cases although not exclusively in the clear cells, many of which showed no positivity. Two of our examples of the botryoid variety were different histologically, being lined predominantly by non keratinizing stratified squamous epithelium with crowded and pyknotic nuclei and no clear cells. One case contained melanin while another showed epithelial crypt formation and superficial palisaded low columnar cells as seen in the glandular odontogenic cyst. This raised the question of whether the latter may form part of the clinicopathologic spectrum of lateral periodontal cyst. The histogenesis of lateral periodontal cysts is uncertain but we favour origin from reduced enamel epithelium. PMID- 1501156 TI - Enhanced prostaglandin biosynthesis in human gingival fibroblasts isolated from patients treated with phenytoin. AB - Prostaglandin E2 (PGE2) formation was studied in human gingival fibroblasts derived from three epileptic patients before and after 9 months of phenytoin (PHT) therapy. Interleukin 1 (IL-1 alpha; 0.3-6.0 ng/ml), (IL-1 beta; 10-1000 pg/ml) and tumour necrosis factor (TNF alpha; 0.01-0.1 microgram/ml) dose dependently stimulated the formation of PGE2 in 24 h cultures. In fibroblasts, derived after 9 months of PHT therapy, IL-1 alpha, IL-1 beta and TNF alpha induced a significantly higher formation of PGE2 compared to that in fibroblasts derived before PHT therapy. IL-1 beta induced a significantly higher release also of 3H-arachidonic acid (3H-AA) from prelabelled PHT fibroblasts compared to that in prelabelled gingival fibroblasts isolated before the drug therapy. Addition of exogenous AA caused a spontaneous increase of PGE2 formation in PHT fibroblasts compared to that in fibroblasts isolated before the PHT treatment. The results indicate that PHT medication results in an upregulation of prostanoid formation in gingival fibroblasts partly due to an increased phospholipase A2 activity and partly due to an increased cyclooxygenase activity. PMID- 1501157 TI - Distribution of fibronectin in healthy, inflamed and drug-induced gingival hyperplasia. AB - The distribution of fibronectin (FN) in the healthy, inflamed and hyperplastic human gingiva was investigated by indirect immunofluorescence. FN appeared as a fibrillar structure in the lamina propria of the healthy gingivae. In the inflamed specimens, FN demonstrated parallel fibres, especially in the coronal areas of the tissue. In the phenytoin gingival overgrowth, tissue FN was observed as thin fibres with variable length. The thin fibres gave the appearance of penetrating the basement membrane of the epithelium. Cyclosporin A gingival enlargement could be differentiated by phenytoin lesions because of the higher length and the parallel distribution of the FN. Finally, FN was observed in the nifedipine gingival overgrowth, where a microfibrillar delicate network gave the appearance of a "cloud"-pattern of distribution. In all of the specimens, blood vessels and nerves could not be stained. These findings show that FN distribution could differentiate the structure of the gingival lesions. PMID- 1501158 TI - Prevalence of betel quid chewing habit in Taiwan and related sociodemographic factors. AB - The prevalence of betel quid chewing habit in Taiwan was surveyed in a group of Chinese people from Kaohsiung city and in a second group from the aboriginal inhabitants of South Taiwan. In all 1299 participants constituted Group 1 (85.2% response rate) and 827 Group 2 (70.1% response rate). People were interviewed in their homes in house-to-house survey, according to a structured questionnaire developed and evaluated by the authors. Of the Kaohsiung inhabitants covering all ages and both sexes, 6% was a current betel chewer and 4% was an ex-chewer, whereas 42% of the aborigines aged over 15 yr was a current chewer and 1% an ex chewer. Lifetime prevalence was 10%. Betel chewing enjoys islandwide popularity among the 20 million inhabitants of Taiwan; the number of current and ex-users was estimated at 2.0 million (95% CI 1.6-2.4 million). The betel quid was prepared in two different ways. In one, used mainly by aborigines, fresh areca nut was simply wrapped with betel leaf and in another, popular mainly among Chinese, a lengthwise piece of betel fruit and lime paste was sandwiched between two halves of an areca nut. A high proportion of chewers was also a smoker and drinker, but tobacco was not found to be chewed together with betel quid. Consumption varied between 14 to 23 portions per day, with individual frequencies ranging widely from 1 to over 200 portions a day. A statistical analysis of sociodemographic factors showed that lesser educated older men, blue collar workers, smokers and drinkers were the likeliest betel chewers. PMID- 1501159 TI - Oral-dental findings in dyskeratosis congenita. AB - A 13-yr-old girl with dyskeratosis congenita is presented. Besides oral leukoplakia and nail dystrophies, there was evidence of pancytopenia, growth retardation, alopecia, mental retardation and microcephaly. The oral findings included caries, gingival recession, short-blunted roots, gingival bleeding, tooth mobility and severe alveolar bone loss resembling juvenile periodontitis. PMID- 1501160 TI - Compound odontoma erupting in the mouth: 4-year follow-up of a clinical case. AB - A case of a compound odontoma erupting in the oral cavity is presented: a follow up study of 4 yr has been performed evaluating the possible relationship with a previous dental trauma. A discussion is presented concerning the etiologic aspects, clinical signs, diagnostic aids and therapeutic approaches to this type of lesion. PMID- 1501161 TI - Alternative restorative approach: a clinical report. AB - This clinical report describes a technique for restoring a maxillary right posterior segment using a combination of a conventional full-coverage retainer and adhesive resin-bonded retainer with a nonrigid connection, periodontal ridge augmentation, and a coronal-radicular amalgam alloy core. A technique has been outlined that allows for the preservation of the maximum amount of natural tooth structure while restoring a maxillary right posterior segment. PMID- 1501162 TI - Implant restoration following removal of an odontogenic keratocyst: a clinical report. PMID- 1501164 TI - Use of a scanning laser three-dimensional digitizer to evaluate dimensional accuracy of dental impression materials. AB - A steel die was machined to represent a dental arch with teeth prepared for complete crowns. Impressions and casts were made from the die, and critical dimensions were measured by two methods--one using micrometers and the other a scanning laser three-dimensional (3-D) digitizer. The digitizer recorded measurements were more precise than the micrometer's and virtually eliminated operator error because the acquisition of data was automatic. The digitizer could also be useful for high-precision analyses of the dimensional accuracy of dental impression materials, but the cost and complexity of the instrument makes it less desirable for low-precision work. PMID- 1501163 TI - Duplication of anterior provisional fixed partial dentures for the final restoration. AB - Using the provisional restoration as a testing ground to increase the predictability of a final restoration is well understood. With the resolution of issues through a well-developed provisional restoration comes the challenge of duplicating its contours in the final prosthesis. A method is described using elastomer impression putty and a molten wax technique by which the contours of a provisional anterior fixed partial denture can be duplicated. The described method is particularly useful when the replication of a specific irregular tooth arrangement is mandated. PMID- 1501165 TI - An alternative orientation of nonrigid connectors in fixed partial dentures. AB - Nonrigid connectors have been advocated for fixed partial dentures. However, space limitations may require overreduction of the preparation or overcontouring of the retainer to place the keyway within the retainer wall. An inverted orientation of the nonrigid connector can resolve these problems. With this design, the key is attached to the distal surface of the mesial retainer in a dual-abutment fixed partial denture, and the keyway is incorporated in the mesial surface of the pontic. This inverted orientation offers several advantages with few disadvantages. PMID- 1501166 TI - Resin-bonded prostheses for posterior teeth. AB - This study evaluated fixed partial dentures bonded with resin to dentin on posterior teeth with minimal tooth preparation. The patients included were missing at least one premolar or first molar. The abutment teeth next to the modification spaces were moderately restored with MOD or class II restorations on most of the teeth. A total of 20 patients with 23 fixed partial dentures were included in the study. After removal of existing restorations, the abutment teeth were prepared to eliminate undercuts on the perimeter of the preparations. Undercut areas within the preparation were not filled but were blocked out later in the laboratory. The fixed partial dentures employed inlays as retainers for a metal ceramic pontic. The metal framework was cast in a high noble gold alloy. The areas of the retainers to be bonded were treated with the Kulzer Silicoater method. Immediately before cementation, enamel was etched and exposed dentin was treated with Gluma. Kerr's resin bonded bridge cement was used for cementation. Patients were recalled after periods of 1 week, 1 month, 6 months, 1 year, 2 years, and 4 years for evaluation. None of the restorations lost retention and no major adverse effects were observed in the 4-year follow-up period. PMID- 1501167 TI - Three-dimensional finite element stress analysis of a cantilever fixed partial denture. AB - A three-dimensional mathematical model was generated, representing a three-unit cantilever fixed partial denture and its supporting mandibular structures. First and second premolars were used as abutments with one posterior cantilever pontic. A 5 lb vertical load was applied to the pontic. Vertical and horizontal stresses were analyzed by means of a three-dimensional finite element stress analysis technique. The results showed that a cantilever pontic creates considerable compressive stress on the abutment nearest to the pontic and produces tensile stress on the abutment farthest from the pontic. PMID- 1501168 TI - In vitro evaluation of dynamic fluid displacement in dentinal tubules activated on pin placement. AB - The use of cemented, friction-lock, and self-threading pins for improving retention has been essential for treatment in restorative dentistry, with the self-threading pin considered to be the most retentive. Cavity varnish has been suggested to prevent microleakage around pins. This study investigated the insertion of a self-threading pin when the pinhole was filled with a liquid dye. The results showed that pinholes filled with dye before pin placement had measurable dye displacement. Pinholes without pins displayed no measurable dye displacement through the dentin; this was also true when the dye fluid was removed before the pin placement. However, the dye in pinholes was displaced toward the path of least resistance, and fluid in a pinhole can contribute to crazing of the dentin during placement. PMID- 1501169 TI - A drilling technique to improve the retention of self-threading pins. AB - This study determined the effect of a modification of the drilling technique on the retention of self-threading pins. The drilling technique in two stages significantly increased the retention of self-threading pins. PMID- 1501170 TI - Effect of bonded amalgam on the fracture resistance of teeth. AB - The purpose of this study was to determine whether amalgam bonded to tooth structure with an adhesive resin cement can increase the fracture resistance of restored teeth. Extracted paired upper premolars were prepared for G.V. Black type mesioocclusodistal amalgam restorations. In one tooth of each pair (the experimental group), the enamel walls were etched with phosphoric acid and were painted with an adhesive resin (Panavia), and amalgam was condensed and carved. For the other tooth in each pair (the control group), amalgam was placed in the same manner but was not etched and lined with resin. The teeth were thermocycled and mounted for testing and then were loaded until fracture. A significant difference (p less than 0.05, the paired Student's t-test) was found in the force needed to fracture the bonded amalgam group (70.5 +/- 21.6 kg) compared with that needed to fracture the conventional amalgam group (60.3 +/- 16.8 kg). SEM examination of fractures at the interface occurred predominantly within the resin. PMID- 1501171 TI - Efficient amalgam core elimination and root preservation with ultrasonic instrumentation. AB - An efficient ultrasonic vibratory energy technique for the elimination of deeply placed amalgam core in an endodontically treated tooth is presented. Root integrity is ensured by avoiding complete reliance on rotary burs for the removal of the obstructing alloy. PMID- 1501172 TI - Comparison of retentive properties of four post systems. AB - This study compared the retention of posts in the root for various diameters (1.3 mm and 1.6 mm) of three prefabricated post systems (Unity, Filpost, and Brasseler) with that of the previously reported No. 1 and No. 2 Flexi-Post systems. The experiment was divided into three groups comprising 10 samples for each post system studied. In group 2, the Filpost system was cemented both with a resin cement and zinc phosphate cement. Retention values were obtained with a modified universal testing machine. The retention of 1.3 mm posts from most to least retentive was Flexi-Post (zinc phosphate) greater than Filpost (zinc phosphate) greater than Filpost (resin) greater than Brasseler (zinc phosphate), greater than Unity (resin). The retention of 1.6 mm posts from most to least was Flexi-Post (zinc phosphate) greater than Filpost (zinc phosphate) greater than Brasseler (zinc phosphate), Unity (resin) greater than Filpost (resin). The Filpost system achieved higher retention with zinc phosphate cement than it did with resin cement. PMID- 1501173 TI - Retentive strength, disintegration, and marginal quality of luting cements. AB - This study evaluated the retention of complete crowns by using five different methods of cementation. Complete crowns were prepared with standardized dimensions on extracted human molars. Metal crowns were cast with a high noble gold ceramic alloy and were cemented with zinc phosphate cement, glass ionomer cement, composite resin cement, composite resin cement with a dentinal bonding agent, and adhesive resin cement. The retention was measured by subjecting the specimens to tensile load until fracture occurred. The disintegration was measured according to American Dental Association Specification No. 8, and the condition of the cements at the margins of crowns was analyzed by use of a scanning electron microscope. Kruskal-Wallis one-way analysis of variance revealed statistically significant differences between the mean retentive strengths. The retention of the zinc phosphate and the glass ionomer groups was significantly different from that of the adhesive resin group. The retention of the adhesive resin cement was 65% greater than the retention of the composite resin and the composite resin/dentinal bonding agent group, but the Mann-Whitney Wilcoxon rank sum test did not depict this difference as significant. The mean +/ SD of the disintegration for the zinc phosphate, the glass ionomer cement, and the composite resin cement was 0.025 +/- 0.013, 0.023 +/- 0.011, and 0.017 +/- 0.001, respectively. The scanning electron microscope analysis of the margins revealed that the composite resin cement was almost intact, the zinc phosphate was subjected to limited disintegration, and the glass ionomer displayed the worst marginal integrity. PMID- 1501174 TI - The degree of zinc phosphate cement coverage of complete crown preparations and its effect on crown retention. AB - This investigation examined the amount of retentive area covered by cement under complete coverage crowns and its effect on retention. Sixty crowns of self-cured acrylic resin were prepared on 60 identical brass dies and were divided into six groups of 10 crowns each according to different cement applications. The results showed that retention was dependent on the amount of retentive area covered by the cement. The amount of cement in the occlusal part of the cementation space did not affect retention. PMID- 1501175 TI - Dimensional accuracy of castable apatite ceramic crowns: the influence of heat treatment on dimensional changes and distortion of crowns. AB - Castable apatite ceramic crowns are subjected to heat treatment during crystallizing and during coloring after casting. The dimensional accuracy of the heat-treated crowns was investigated with respect to its influence on dimensional changes in castable apatite ceramic crowns and on distortion of the interior of the crowns, using two investment techniques and a three-coordinate measuring machine. Dimensional changes were not influenced by the number of coloring firings. Distortion of the interior of crowns was slightly outward at the gingival plane. Shrinkage because of crystallizing was approximately 20 microns and the shrinkage of the gingival plane was equal to that of the occlusal plane. PMID- 1501176 TI - Thermal cycling distortion of metal ceramics: Part II--Etiology. AB - The three-dimensional geometry of conventional fixed prostheses complicates the study of the thermal cycling distortion in metal ceramic alloys. Any explanation of the etiology of thermal cycling distortion in metal ceramic restorations must account for the observed magnitude, timing, and direction of the deformation. The simplified experimental geometry developed in Part I was applied to elucidate the etiologic factors involved in metal ceramic deformation. Techniques to minimize the thermal cycling distortion were also studied. It was found that all of the significant distortion occurred during the first thermal cycling of the alloy (oxidation) and that no distortion resulted from the application of body porcelain. The specimens that were cold worked and then oxidized had significantly more distortion than any other group. A significant reduction in distortion was observed when the initial thermal cycling was completed before the specimens were cold worked. It was determined that the release of casting- and cold working-induced stresses had a synergistic effect. PMID- 1501177 TI - Comparison of vertical movement occurring during loading of distal-extension removable partial denture bases made by three impression techniques. AB - Although the altered-cast impression technique attains stability and controlled tissue support for distal-extension removable partial dentures, the procedure is time-consuming and technique-sensitive. This study clinically compared the vertical displacement of distal-extension removable partial dentures made from different impression techniques. The impressions studied were the altered-cast impression, an impression made from a border-molded custom tray, and a stock tray irreversible hydrocolloid impression that served as a control. A post hoc analysis, using a Tukey Q-test, exhibited significance (p less than 0.01) between the two impression techniques after intraoral loading was performed. Although statistically significant, the 0.19 mm difference between the impression techniques may or may not be clinically relevant. Additional research is required in this area. PMID- 1501178 TI - Evaluation of the accuracy of cast reorientation to a surveyor by prosthodontic residents. AB - This study investigated the accuracy of a group of evaluators in reestablishing the orientation of a tripoded master cast to a surveyor instrument. Three prosthodontic residents served as evaluators to reestablish the tilt of a previously tripoded cast with three known reference coordinates. The distance from the known to the reference point was recorded for the three points in four trials by a judge with a machinist height gauge. Analysis of variance revealed a significant difference between the evaluator cast position and the known reference position. The investigation demonstrated +/- 0.2 mm errors at each of the three locations; 0.3-degree angulation errors occurred in reestablishing the tilt of the master cast in relation to the surveyor. PMID- 1501179 TI - Masticatory ability, denture quality, and oral conditions in edentulous subjects. AB - This study investigated the relationships between the ability of 38 patients with complete dentures to comminute a tough artificial test food and their answers to questions about the chewing experience. Also, clinical assessments were made of denture quality and oral conditions. Significant but weak relationships were found between the ability to comminute the test food and the subjective chewing experience as well as the degree of resorption of the mandibular residual ridge. Masticatory ability is conceivably determined by many other factors as well. Results indicate that dentists cannot rely on asking denture wearers about chewing problems and clinical responses with respect to oral conditions and denture quality for predicting those patients' masticatory abilities. The ability of wearers of complete dentures to comminute tough foods should be determined individually by a series of chewing tests. PMID- 1501180 TI - The practice of complete denture prosthodontics by selected dental graduates. AB - Graduates of a dental school in the southeastern United States were surveyed for the procedures they used in practicing complete denture prosthodontics. Of the 530 graduates representing 15 graduating classes, 80% returned the questionnaires. Most respondents (94.8%) made complete dentures, but only 3.5% devoted more than 20% of their practice time to this phase of prosthodontics. In practice, the average graduate performed approximately one half of the techniques that had been judged academically to be clinically essential. Compliance decreased proportionately with the number of years in practice. Factors affecting compliance include the influence of peer practitioners and continuing education courses. The content of the predoctoral curriculum needs to be reviewed for its relevancy to continuing education and to dental practice. PMID- 1501181 TI - Study of the sagittal condylar path in edentulous patients. AB - The inclination of the condylar path is a fundamental consideration in the prosthodontic treatment of the totally edentulous patient. The authors studied 55 patients at the University of the Basque Country, making three graphic registrations of the protrusive condylar movement on each side. Three examiners, working independently, used the tangential method to measure the angulation relative to Camper's plane. The results show that angulation varies greatly on each side and from one individual to another. In the treatment of edentulous patients, graphic registering techniques that can determine these variations should be used. PMID- 1501182 TI - Standardized radiographs of the alveolar crest around implants in the mandible. AB - The techniques currently used for standardized longitudinal radiographic evaluation of the supporting bone around dental implants are not suitable for general application. An aiming device is described for intraoral radiography used to evaluate the crestal bone height around dental implants used as retention for overdentures. This aiming device has been tested on four different implant systems by four dentists. Error analysis of serial radiographs indicates small deviations in reproducibility. It is concluded that this method is suitable for routine evaluation of dental implants. PMID- 1501183 TI - Tissue compatibility and stability of a new zirconia ceramic in vivo. AB - Tissue reaction and stability of partially stabilized zirconia ceramic in vivo was evaluated with the use of the subcutaneous implantation test. During the experimental period, zirconia ceramic was completely encapsulated by a thin fibrous connective tissue with less than 80 microns thickness. No changes of weight and 3-point bending strength were detected after 12 months of implantation. The result suggests that zirconia ceramic is biocompatible and no degradation of zirconia ceramic occurred. PMID- 1501184 TI - Effects of environmental factors on maxillofacial elastomers: Part I--Literature review. AB - Part I of a four-part report presents a comprehensive review of the literature pertaining to physical property testing of materials for facial and somatoprostheses. The report was conducted in preparation for testing four current maxillofacial elastomers: MDX 4-4210, Silastic 4-4515, Medical Adhesive type A, and Epithane-3, and two recently introduced materials: Silicone A-2186 and Silicone A-102. PMID- 1501185 TI - Biocompatibility testing of a silicone maxillofacial prosthetic elastomer: soft tissue study in primates. AB - Little information exists on the biocompatibility of maxillofacial prosthetic materials. Cosmesil material is a purpose-designed facial prosthetic elastomer that has an established clinical profile in humans but results of biocompatibility testing have not been published. Cosmesil, acrylic resin (positive control), black surgical gutta-percha (negative control), and Silastic 382 material (Dow Corning, Midland, Mich.) (reference control) were processed as custom-designed implants. The implants were inserted into five chacma baboons for a 12-week period in intraosseous, subperiosteal, submucosal, and intramuscular sites. The histologic assessment was based on a modified form of the FDI-ISO Technical Report 7405 for subcutaneous implants. An evaluation was made of capsule formation and inflammatory response. The statistical analysis involved a three-way ANOVA and a Tukey-Kramer Student range test. The critical level of statistical significance chosen was p less than 0.05. The study found that gutta percha provoked a statistically significantly thicker capsule and a severe inflammatory response. Acrylic resin, Cosmesil material, and Silastic 382 material produced capsule formations and an inflammatory response that did not differ significantly. Cosmesil material is not manufactured as an implant material, but from the present findings it is considered acceptably biocompatible for its intended use where there may be contact with internal tissue spaces that are contiguous to external surfaces. PMID- 1501186 TI - Surgical obturation using a gated prosthesis. AB - A description is given for the fabrication of a stable, versatile surgical obturator prosthesis for the dentate patient. The wrought wire and acrylic resin prosthesis is based on the swinglock concept and allows for simple transition from wire-retained to removable obturation early in patient recovery. By using such a prosthesis, interim obturator fabrication may be delayed if the practitioner believes further healing to be desirable. In some patients, transition directly to definitive obturation may be considered. PMID- 1501188 TI - Light-cured combination obturator prosthesis. AB - A technique for the fabrication of an open combination (hard-resilient) obturator prosthesis with VLC materials for patients undergoing partially edentulous maxillectomy is described. VLC denture resins and resilient liners are an exciting innovation in prosthodontic treatment and offer the maxillofacial prosthodontist a wider choice of treatment modalities. The technique and the resultant obturator prosthesis have the following advantages: 1. The ease and rapidity of the technique saves time for both the patient and the maxillofacial prosthodontist by introducing the open obturator prosthesis at the earliest opportunity. 2. The combination open obturator prosthesis provides a stable record base for securing jaw relation records. 3. The thickness and resiliency of the obturator prosthesis can be managed more easily. Flexibility and resiliency can be modified by the thickness of the resilient liner or by adding a rigid scaffolding according to the clinical requirements. 4. Prostheses are easy to repair or modify by using increments of VLC hard or resilient materials. 5. The combination VLC obturator prosthesis provides stability, retention, and decreased weight and obduration of residual palatal defects. 6. The technique can be used for partially edentulous or edentulous patients after maxillary resection. PMID- 1501187 TI - A foam impression technique for maxillary defects. AB - This article presents a technique used to overcome the problems of withdrawal of maxillectomy defect impressions with or without limited space as the result of trismus. PMID- 1501189 TI - Reproducibility of mandibular motion and muscle activity levels using a commercial computer recording system. AB - A commercial computer recording system (BioPak) was tested for its accuracy and reproducibility in recording mandibular motion and muscle activity levels (EMG). Accuracy of measurements of mandibular motion was tested using sliding calipers. Accuracy of muscle activity levels was checked with a sine-wave calibration signal of known amplitude and frequency. Reproducibility of motion and of EMG was made using five control subjects each tested on 3 separate days. Computer measurements of motion were found to require correction for nonlinearity at openings beyond 45 mm. Most maximum voluntary excursions were found to be more reproducible than motions during mastication. However, lateral deviation during opening was strongly affected by magnet orientation and varied greatly between trials. Electromyographic recordings were distorted by improper treatment of high frequency components of the signal and also varied greatly between trials. This study suggests that the BioPak system may indicate changes in some measures of mandibular motion and EMG levels in patients for whom no changes have occurred. PMID- 1501190 TI - The use of transcranial stimulation in the fabrication of an occlusal splint. AB - An alternative method for fabricating occlusal splints by means of electric transcortical stimulation is presented. Ensuing results in one patient suggest neuromuscular benefits. However, the centric occlusal position determined by this method is a painful procedure because of electric stimulation on the scalp. Further and extensive investigations must be carried out to assess the clinical benefits and limits of this method. PMID- 1501191 TI - Principles for selecting interocclusal records for articulation of dentate and partially dentate casts. AB - Minimizing the orientation error of the working and opposing casts on the articulator should reduce the extent of intraoral adjustment of restorations before their placement. This article defines and reviews principles such as the tripod of vertical support (three widely spaced occlusal contacts) and adequate horizontal stability, which enable opposing dental casts to be held together in a stable and reproducible manner at the time the mandibular cast is mounted to the articulator. During the restoration of the dentate or partially dentate patient, where restoration is to be coincident with pretreatment maximum intercuspation, the goal of the interocclusal record is to provide stability and/or support for the casts. The types of interocclusal records are organized into categories and designs based upon the remaining vertical support and horizontal stability of the dentition. The clinical indications, limitations, design, and composition of a variety of records for each of these categories are reviewed and discussed. PMID- 1501192 TI - Comparison of bond strength of six soft denture liners to denture base resin. AB - The bond strength of six commercial soft denture liners was evaluated using a modified tensile test. The soft denture liners investigated were Prolastic, VinaSoft, Flexor, Molloplast-B, Novus, and Super-Soft. The samples were processed according to the manufacturers' instructions to cured denture base resin (polymethyl methacrylate; PMMA). The soft denture liners were 10 x 10 x 3 mm and were processed between two PMMA blocks. The samples were placed in tension until failure. The mode of failure, cohesive or adhesive, was also recorded. The results of this study showed that the bond strength is related to the components of the materials. Prolastic, VinaSoft, and Flexor had the lowest bond strength to cured PMMA and ranged from 9.6 to 11.3 kg/cm2. Super-Soft, Novus, and Molloplast B demonstrated better bond strengths and ranged from 16.7 to 17.6 kg/cm2. The bond strength of Novus could be improved by using the recommended bonding agent and bonded Novus at 26.1 kg/cm2 had the highest bond strength of all materials tested. PMID- 1501193 TI - Flexible casts used in making indirect interim restorations. AB - This article describes a procedure for making indirect interim restorations from a cast and dies made of polyvinyl siloxane impression material. The use of these flexible casts and dies facilitates the removal of the polymerized resin from the cast and the rapid set of the polyvinyl materials reduces the time involved in making the indirect interim restorations. PMID- 1501194 TI - The usage period of dentures and their residual monomer contents. AB - The quantity of residual monomer content in 24 maxillary dentures was detected by gas liquid chromatography. The residual monomer contents tended to be lower in dentures used for long periods than in those used for short periods. Decreases in the quantities of residual monomer in acrylic resin dentures as a result of aging can be expressed in a hyperbola. The fitted curve also suggests that most of the loss could be accomplished in 5 years; however, complete loss of the residual monomer content takes many years. PMID- 1501195 TI - Uncomplicated removal of a double abutment fixed partial denture with one loose abutment. PMID- 1501196 TI - Preventing distortion of removable partial denture frameworks during deflasking process. PMID- 1501197 TI - Technique for two-stage retrofitted cast post and core. PMID- 1501198 TI - Diagnostic tests used in determining the role of occlusion in temporomandibular joint disorders. PMID- 1501199 TI - Diagnostic tests used in determining the role of occlusion in temporomandibular disorders. PMID- 1501200 TI - Restoring teeth following crown lengthening procedure. PMID- 1501202 TI - Interaction between inoculated allogeneic lymphocytes and fetal rats. AB - Interaction between allogeneic lymphocytes and 12-20-day gestation rat fetuses was examined in vitro and in vivo. Intravenous injection of lymphocytes was achieved either by in vitro cannulation of the vitelline vein followed by culture of the whole fetus, or of its organs, or by in utero cannulation of the vitelline vein through the uterine wall. Cytotoxic reactions on the part of the inoculated allogeneic lymphocytes against fetal tissue could not be detected in the young hosts. The fetal spleen, mesentery and intestine appeared to have a specific affinity for adult lymphocytes from the earliest gestational age examined. PMID- 1501201 TI - Immunosuppressive activity in the rat seminiferous tubules. AB - Rat seminiferous tubule segments in defined stages of the epithelial cycle were isolated by transillumination-assisted microdissection. The segments were cultured together with ConA-stimulated peripheral blood lymphocytes (PBL) and incorporation of 3H-labelled thymidine was measured. Tubule segments in stages II VIII of the seminiferous epithelial cycle inhibited PBL proliferation significantly more than stages IX-I. Inhibition was lowest in stages IX-XII and increased progressively to reach a maximum in stages II-VIII. In a more detailed analysis, tubules in stages V and VI inhibited PBL proliferation significantly less than stage II tubules. No significant difference was observed between stages II and VII. The immunosuppressive activity had molecular weights of approximately 25 kDa and approximately 65 kDa in stage II-VIII seminiferous tubules. In stage II-VI seminiferous tubules activity was present also at approximately 10 kDa. The results suggest that the seminiferous tubules produce high-molecular weight immunosuppressive activity in a stage-dependent way. In addition to its contribution to the immunologically privileged milieu of the testis this activity may also be involved in the physiological regulation of DNA synthesis in the seminiferous epithelium. PMID- 1501203 TI - The influence of intravenously introduced allogeneic lymphocytes on fetal rats. AB - Semi-allogeneic or allogeneic bone marrow cells, or allogeneic spleen cells, were injected in utero into PVG, DA and Fischer rat fetuses at 15-18 days of gestation via the vitelline vein. Prenatal (PVG x DA) F1 bone marrow cell inoculation produced allograft tolerance far more frequently in DA recipients than in PVG recipients. Inoculation of allogeneic or semi-allogeneic spleen cells into rat fetuses failed to induce allograft tolerance but sensitized the recipients. The observation that Fischer recipients could be rendered tolerant to skin allografts by prenatal inoculation of PVG, but not DA, bone marrow cells indicated that variation in susceptibility to tolerance induction among different donor recipient strain combinations is unlikely to be explicable on the basis of strain differences in developmental maturity of the host immune system. PMID- 1501204 TI - Preferential synthesis of asymmetric antibodies in rats immunized with paternal particulate antigens. Effect on pregnancy. AB - The effect of immunization of female Fischer rats with particulate (spleen cells) (group I) or soluble (supernatant of disintegrated spleen cells) (group II) paternal antigens previous to mating with Buffalo rats was investigated. The percentage of asymmetric IgG molecules in the serum of rats inoculated with particulate antigens was 38% while in those injected with soluble antigens it was 29% and 28% in non-immunized animals. These percentages further increased during pregnancy to 45%, 38% and 37%, respectively. The antipaternal antibody titres, as determined by indirect immunofluorescence (IIF), was much higher in the animals immunized with particulate antigens but the effector activity, judged by complement fixation, was similar in both groups. The same values were observed at the time of mating (after 3 months of immunization) and at day 17 of pregnancy. Fetus and placenta weights and offspring survival were equally greater in group I than in group II or non-immunized rats (group III). The results obtained indicate the preferential synthesis of antipaternal IgG asymmetric antibodies in rats injected with particulate antigens previous to mating and suggests a beneficial effect of these antibodies in pregnancy. PMID- 1501205 TI - Relative immunosuppressive activity of human seminal prostaglandins. AB - Human seminal plasma contains uniquely high concentrations of prostaglandins of the E series which are believed to contribute to its immunosuppressive effects in vivo. In order to obtain further insight into their activity we have compared the immunosuppressive properties in vitro of PGE1, PGE2 and 19-OH PGE using three immunological systems known to be modulated by prostaglandins, namely, mitogen induced lymphocyte proliferation, IL-2 and transferrin receptor expression and NK cell mediated cytotoxicity. These studies revealed that PGE1 and PGE2 exerted a greater immunosuppressive effect than 19-OH PGE, but considerably higher levels of 19-OH PGE in semen might contribute the majority of immunosuppressive activity in vivo. Our studies also show that the lower stability of 19-OH PGE in culture media may be responsible for its lower immunosuppressive effect observed in vitro. PMID- 1501206 TI - Antifertility effect of active immunization with ZP4 glycoprotein family of porcine zona pellucida in hamsters. AB - Female golden hamsters were immunized with solubilized porcine zona pellucida (s PZP) or ZP4 glycoprotein family isolated from s-PZP by preparative SDS-PAGE. Both antigen preparations induced production of antibodies which reacted not only with porcine zona pellucida but also with the hamster zona pellucida. The hamsters immunized with solubilized porcine zona pellucida mainly produced antibodies reactive to ZP3, while the hamsters immunized with ZP4 mainly produced antibodies reactive to ZP4. The former animals became permanently infertile but the infertility in the latter animals was temporary and they became pregnant later. Histological studies revealed that the ovarian follicles in hamsters immunized with s-PZP were completely destroyed leaving only atrophic follicle-like cell clusters, while in the ovaries of hamsters immunized with ZP4 a number of small follicles with oocytes remained intact. These observations are encouraging for the further characterization of the ZP4 antigens as candidates for the development of a contraceptive vaccine. PMID- 1501207 TI - Interleukin-3-like activity levels in pregnant women: possible modulation by progesterone. AB - Human interleukin-3-like activity (IL-3-LA), a factor possessing similar characteristics to interleukin-3 and having clony stimulating factor (CSF) activity, has recently been defined. In the present study, IL-3-LA levels in the sera of women before and after delivery were examined. The results indicate a significant increase in IL-3-LA levels in women before delivery as compared to IL 3-LA levels after delivery or to non-pregnant healthy women. The ability of mononuclear cells from women before and after delivery to produce IL-3-LA was similar to that of mononuclear cells from cord blood. In addition, the effect of progesterone on in vitro IL-3-LA production was examined and a stimulatory dose dependent effect was observed. These observations point to the hypothesis that during pregnancy IL-3-LA levels are modulated by progesterone. With placental loss, the IL-3-LA in the sera decreases, although the mononuclear cells previously affected by the hormone continue to produce cytokines. PMID- 1501208 TI - Overberg research projects. XII. The efficacy of an albendazole slow-release capsule in the control of nematode parasites of sheep. AB - Albendazole intra-ruminal slow-release capsules (SRC) administered to sheep grazing on irrigated pastures in the southern Cape Province, controlled Trichostrongylus for 91 d and Haemonchus and Teladorsagia for 61 d. Treating sheep with the SRC at 47 to 61 d intervals over a period of 10 months, significantly (P less than 0.05) reduced the infective potential of the pasture. Compared with sheep which received 2 disophenol and 3 broad spectrum anthelmintic treatments during the same period, the SRC reduced the infective potential of the pasture by 71.6%, while weekly drenching with albendazole over the same period, resulted in a significant (P less than 0.05) increase (73.4%) in the infective potential of the pasture. PMID- 1501209 TI - Tiletamine hydrochloride in combination with zolazepam hydrochloride as an anaesthetic agent in sheep. AB - The anaesthetic effects of Zoletil, a 1:1 combination of tiletamine and zolazepam, was evaluated in 10 sheep. The optimum dose of this preparation was found to be 12 mg kg-1. It produced rapid induction, cataleptoid anaesthesia and smooth recovery with a minimal effect on blood pressure. Individual sheep, however, displayed variable reactions to the anaesthetic. Atropine premedication at 0.04 mg kg-1 did not have any significant effect on either heart rate or blood pressure when compared to Zoletil alone. PMID- 1501210 TI - Necropsies of eight horses infected with Strongylus equinus and Strongylus edentatus. AB - Ponies (n = 8) approximately 18 months old, were infected with 20,000 to 30,000 infective larvae of Strongylus equinus with less than 10% contamination with Strongylus edentatus larvae and necropsied 7 months post-infection. Lesions were present in the omentum, liver, pancreas, ventral colon, caecum and occasionally in the lungs. There were numerous intraabdominal adhesions and severe multiple granulomatous omentitis. Pancreatic damage, which characterises S. equinus, was exceptionally mild and was manifested mainly by slight periductular infiltration of eosinophils. Granulomas associated with larvae were found in the connective tissue associated with the pancreas. Larvae were recovered from the flanks, the peritoneum, the caecum and the kidney. Larval recovery was low, with a high percentage of the total number of larvae recovered in some of the carcasses being S. edentatus. PMID- 1501211 TI - Malignant mesothelioma in a seven-week-old puppy. AB - A case of diffuse malignant peritoneal mesothelioma in a 7-week-old puppy is reported. The puppy presented with a recurrent abdominal effusion. An exploratory laparotomy revealed extensive adhesions. Necropsy findings included pleural thickening, and enlargement of the renal and anterior mediastinal lymph nodes. The microscopic features were typical of primary desmoplastic diffuse mesothelioma of the peritoneum and pleura with secondary lymph node metastasis (renal and anterior mediastinal). The tumour was classified as epithelial in type. The extent of the tumour and the distant metastasis were considered to reflect a high degree of malignancy. A congenital origin was suspected. PMID- 1501212 TI - Cutaneous leishmaniasis in a sheep. AB - A case of cutaneous leishmaniasis in a sheep from the Eastern Transvaal is described. The pinna of one ear was swollen and the overlying skin thickened and diffusely encrusted. Histopathological examination of a skin biopsy revealed a diffuse dermal infiltration of macrophages, plasma cells and lesser numbers of eosinophils and neutrophils, as well as a few multinucleated giant cells. Macrophages, particularly in the superficial dermis, contained large numbers of small basophilic bodies morphologically compatible with the amastigote stage of Leishmania spp. Changes in the overlying epidermis included orthokeratotic hyperkeratosis, pseudoepitheliomatous hyperplasia with a focal erosion and crust formation. No attempts were made to culture the organism. PMID- 1501213 TI - Putative equine protozoal myeloencephalitis in an imported Arabian filly. PMID- 1501214 TI - Gold medal of the SAVA: 1991. Prof. J. M. W. le Roux. PMID- 1501215 TI - Silver Medal of the SAVA: 1991. Dr. V de Vos. PMID- 1501216 TI - Boswell Award of the SAVA: 1991. Dr. D. G. Catton. PMID- 1501217 TI - Boswell Award of the SAVA: 1991. Dr. P. M. S. Masters. PMID- 1501218 TI - Clinical Award of the SAVA: 1991. Dr. P. C. Cardington. PMID- 1501219 TI - Clinical Award of the SAVA: 1991. Dr. Claire Marshall. PMID- 1501220 TI - Synthesis and biological activity of CCK heptapeptide analogues. Effects of conformational constraints and standard modifications on receptor subtype selectivity, functional activity in vitro, and appetite suppression in vivo. AB - A series of modifications of the CCK7 analogue (des-NH2)Tyr(SO3-)-Nle-Gly-Trp-Nle Asp-Phe-NH2 was prepared and tested for binding to guinea pig CCK-A and CCK-B receptors and in CCK-A-mediated functional assays. Selected analogues also were tested for appetite suppressant activity in rats. Several conformationally restricted residues in the C-terminal tetrapeptide region, including delta Z Phe33, (N-Me)Phe33, (N-Me)Asp32, (N-Me)Leu31, and 3PP31 (3PP = trans-3-n-propyl-L proline) were found to be acceptable modifications at one or both receptor subtypes. The (N-Me)Asp32 and (N-Me)Leu31 modifications afforded potent and selective CCK-A and CCK-B ligands, respectively. SAR studies in the N-terminal acyldipeptide region examined structural requirements for the side chain at position 28, where Gly and Pro replacements were found to possess high affinity at both receptor subtypes. Other conformationally restrictive modifications were less active. All of the analogues that showed high affinity (less than 10 nM) for the CCK-A receptor also were full agonists in amylase release and most were full or nearly full agonists in the phosphoinositide (PI) turnover assay, the most notable exception being the delta Z-Phe33 analogue, which showed 69% of the maximal response in the PI assay. Potent activity in suppression of food intake in rats was found for selected analogues. PMID- 1501221 TI - Design and synthesis of some substrate analogue inhibitors of phospholipase A2 and investigations by NMR and molecular modeling into the binding interactions in the enzyme-inhibitor complex. AB - A series of substrate analogue inhibitors of pancreatic phospholipase A2 has been designed and synthesized. The compounds were tested in a novel dual-screening system based on parallel assays with monomeric and micellar substrates. Intermolecular nuclear Overhauser effects between vinylic protons on one inhibitor and identified active site residues on the bovine pancreatic enzyme have been observed in solution NMR studies of the enzyme-inhibitor complex. It can be deduced from both the biochemical results and the NMR data that the mode of interaction between this type of inhibitor and the active site of phospholipase A2 is essentially the same, irrespective of the presence or absence of an aggregated phospholipid surface. A model of the binding between the enzyme and inhibitor which incorporates the two-dimensional NMR data has been developed. The model can account for the activity of modified inhibitor structures and can be extrapolated to an assessment of the mode of binding of the natural substrate itself. PMID- 1501222 TI - Molecular determinants of the platelet aggregation inhibitory activity of carbamoylpiperidines. AB - A series of alpha,alpha'-bis[3-(N,N-dialkylcarbamoyl)piperidino]-p- xylenes were synthesized and tested for their inhibitory activity on ADP-induced aggregation of human platelets. A parabolic curve was obtained when log 1/C (activity) was plotted against log P (octanol/water partition coefficient). Using this as a model, a new analogue, alpha,alpha'-bis-[3-(N-methyl-N-butylcarbamoyl)piperidino] p-xylen e (3g), was synthesized with a predicted IC50 of 25 microM. When this compound was subsequently evaluated, the IC50 was 22.1 +/- 5.5 microM, demonstrating the applicability of this model. The amide oxygen of the carbamoyl substituent appeared necessary for activity. Thus, for example, when the amide carbonyl group of 3a (IC50 = 44.5 microM) was reduced to CH2, the resulting compound 4 had a dramatically reduced activity, IC50 = 1565 microM. Compound 3a was resolved into (+) and (-) enantiomers and a meso (0) diastereomer using fractional crystallization, diastereomeric tartrate formation, and chiral HPLC. Compared to (-)-3a, the (+) isomer was 15 times more potent when ADP was the agonist and 19 times more active when collagen was used as the agonist. Molecular modeling of R,R- and S,S-3a using the SYBYL program was used to examine their interactions with phosphatidylinositol (PI). There was a better fit between PI and the R,R-3a with the energy of interaction being 17.6 kcal/mol less than that of the S,S-3a/PI complex. Although the absolute stereochemistry of individual enantiomers is not known, this study shows that R,R-3a interacts more favorably with PI than does S,S-3a and that (+)-3a is a more potent inhibitor of human platelet aggregation than (-)-3a. It is postulated that because of their lipophilicity, these compounds penetrate the platelet membrane and are then protonated at the pH of the cytosol. The protonated N then neutralizes the anionic charge on the membrane phosphoinositides, thereby rendering them less susceptible to hydrolysis by phospholipase C. Thus, the determinant parameters for optimum antiplatelet activity in 3-carbamoylpiperidines are (1) the amide carbonyl, (2) appropriate stereochemistry of the 3-substituent and (3) a log P value of about 4.5. PMID- 1501223 TI - DNA-directed alkylating agents. 5. Acridinecarboxamide derivatives of (1,2 diaminoethane)dichloroplatinum(II). AB - A series of acridine-2- and -4-carboxamide-linked analogues of PtenCl2 has been prepared and evaluated for biological activity against several tumor cell lines in vitro and in vivo. The platinum complexes were generally more cytotoxic than the corresponding ligands against wild-type P388 leukemia cells in vitro, with acridine-4-carboxamide complexes being the more effective. In contrast to cisplatin and PtenCl2, the complexes were equally active in vitro against both wild-type and cisplatin-resistant P388 lines. The 4-carboxamide complexes showed high levels of in vivo activity (ILS greater than 100%) against wild-type P388 using a single-dose protocol, and one compound was also significantly active in vivo in a cisplatin-resistant line, against which cisplatin and PtenCl2 are inactive. PMID- 1501224 TI - TSAO analogues. Stereospecific synthesis and anti-HIV-1 activity of 1-[2',5'-bis O-(tert-butyldimethylsilyl)-beta-D-ribofuranosyl]-3'-spiro -5''- (4''-amino 1'',2''-oxathiole 2'',2''-dioxide) pyrimidine and pyrimidine-modified nucleosides. AB - Several analogues of a new lead for anti-HIV-1 agents [1-[2',5'-bis-O-(tert butyldimethylsilyl)-beta-D-ribofuranosyl]-thymine] -3'-spiro-5''-(4''-amino 1'',2''-oxathiole 2'',2''-dioxide) (TSAO) modified at positions N-3, O-4 and C-5 of the thymine moiety, have been prepared and evaluated as inhibitors of HIV-1 replication. A new stereoselective synthetic procedure is described. Reaction of 1,2-di-O-acetyl-5-O-benzoyl-3-C-cyano-3-O-mesyl-D-ribofuranose with pyrimidine bases, followed by treatment with Cs2CO3 afforded stereoselectively, beta-D ribofuranosyl-3'-spiro nucleosides. 2',5'-O-Deacylation and subsequent treatment with tert-butyldimethylsilyl chloride gave the TSAO derivatives. Only those analogues having a tBDMSi group at both the C-5' and C-2' positions of the ribose moiety showed potent anti-HIV-1 activity. The activity ranged from 0.060 microM to 1.0 microM. Introduction of an alkyl or alkenyl function at N-3 of the thymine ring markedly decreased cytotoxicity without affecting the antiviral activity. While markedly active against HIV-1, the TSAO derivatives had no activity against HIV-2 or SIV. They represent the first example of nucleoside analogues with an intact ribose moiety that discriminate between HIV-1 and other retroviruses. PMID- 1501225 TI - Template-directed design of a DNA-DNA cross-linker based upon a bis-tomaymycin duplex adduct. AB - A template-directed approach to the design of a DNA-DNA interstrand cross-linker based upon the structure of a bis-tomaymycin-duplex adduct has been carried out. Tomaymycin is a member of the pyrrolo[1,4]benzodiazepines antitumor antibiotics. In a previous study (F.L. Boyd et al., Biochemistry 1990, 29, 2387-2403), we have shown that two tomaymycin molecules can be covalently bound to a 12-mer duplex molecule, where the drug molecules are on opposite strands six base-pairs apart, and the stereochemistry at the drug bonding site, and orientation in the minor groove, was defined by high-field NMR. This bis-tomaymycin 12-mer duplex adduct maintains the self-complementarity of the duplex and a B-type structure. In the present study we have shown using high-field NMR that this same 12-mer sequence can be truncated by two base pairs so that the two tomaymycin-modified guanines are now only four base-pairs apart, the two species of tomaymycin molecules are still bound with the same stereochemistry and orientation, and the 10-mer duplex adduct maintains its self-complementarity. In a second 10-mer duplex we have shown that changing the bonding sequence from 5'CGA to 5'AGC does not significantly affect the structure of the bis-tomaymycin-duplex adduct. However, when the sequence is rearranged so that the drugs point in a tail-to-tail orientation rather than in the previous head-to-head configuration, there are more than one species of tomaymycin bound to DNA, and, as a consequence, the bis tomaymycin 10-mer duplex adduct loses its self-complementarity. Last, we have used the 10-mer duplex containing the 5'CGA sequence, in which the tomaymycin molecules are oriented head to head, to design an interstrand cross-linking species in which the two drug molecules are linked together with a flexible linker molecule. PMID- 1501226 TI - Synthesis and antifolate evaluation of 10-ethyl-5-methyl-5,10- dideazaaminopterin and an alternative synthesis of 10-ethyl-10- deazaaminopterin (edatrexate). AB - Previous findings suggesting that 5,10-dialkyl-substituted derivatives of 5,10 dideazaaminopterin warranted study as potential antifolates prompted synthesis of 10-ethyl-5-methyl-5,10- dideazaaminopterin (12a). The key step in the synthetic route to 12a was Wittig condensation of the tributylphosphorane derived from 6 (bromomethyl)-2,4-diamino-5-methylpyrido[2,3-d]pyrimidine (7a) with methyl 4 propionylbenzoate. Reaction conditions for the Wittig condensation were developed using the tributylphosphorane prepared from 6-(bromomethyl)-2,4-pteridinediamine (7b) as a model. Each of the respective Wittig products 8a and 8b was obtained in 75-80% yield. Hydrogenation of 8a and 8b at their 9,10-double bond afforded 4 amino-4-deoxy-10-ethyl-5-methyl-5,10-dideazapteroic acid methyl ester (9a) and 4 amino-4-deoxy-10-ethyl-10-deazapteroic acid methyl ester (9b). This route to 9b intersects reported synthetic approaches leading to 10-ethyl-10-deazaaminopterin (10-EDAM, edatrexate), an agent now in advanced clinical trials. Thus the Wittig approach affords an alternative synthetic route to 10-EDAM. Remaining steps were ester hydrolysis of 9a,b to give carboxylic acids 10a,b followed by standard peptide coupling with diethyl L-glutamate to produce diethyl esters 11a,b, which on hydrolysis gave 12a and 10-EDAM (12b), respectively. The relative influx of 12a was enhanced about 3.2-fold over MTX, but as an inhibitor of dihydrofolate reductase (DHFR) from L1210 cells and in the inhibition of L1210 cell growth in vitro, this compound was approximately 20-fold less effective than MTX (DHFR inhibition, Ki = 4.82 +/- 0.60 pM for MTX, 100 pM for 12a; cell growth, IC50 = 3.4 +/- 1.0 nM for MTX, 65 +/- 18 nM for 12a). PMID- 1501227 TI - A pentahalogenated monoterpene from the red alga Portieria hornemannii produces a novel cytotoxicity profile against a diverse panel of human tumor cell lines. AB - A polyhalogenated acyclic monoterpene, 6(R)-bromo-3(S)-(bromomethyl)-7- methyl 2,3,7-trichloro-1-octene (1) was obtained as a major component of the organic extract of the red alga Portieria hornemannii. X-ray diffraction analysis provided the complete structure, including correct placement of the different halogen atoms and determination of the absolute stereochemistry. Detailed NMR analyses provided complete 1H and 13C assignments. Compound 1 exhibited highly differential cytotoxicity against the U.S. National Cancer Institute's new in vitro human tumor cell line screening panel; brain tumor, renal, and colon tumor cell lines were most sensitive to 1, while leukemia and melanoma lines were relatively less sensitive. A second collection of P. hornemanni yielded the novel, monocyclic 2, considerably less cytotoxic and devoid of differential activity. On the basis of its unprecedented cytotoxicity profile in the NCI primary screen, compound 1 has been selected by the NCI Decision Network Committee for preclinical drug development. PMID- 1501228 TI - Sulfonylureas: a new class of cancer chemotherapeutic agents. AB - This study summarizes the antitumor properties of a number of sulofenur thiophene analogs against subcutaneously implanted 6C3HED lymphosarcoma with structural modification of the aryl moiety of the sulfonamide portion of the diarylsulfonylureas. The spectrum of activity of N-(p-chlorophenyl)-N'- [(5 methoxy-2-thienyl)sulfonyl]urea in the HXGC3, VRC5, CX-1, and LX-1 cell lines is also presented. PMID- 1501229 TI - Dispiro-1,2,4,5-tetraoxanes: a new class of antimalarial peroxides. AB - Dispiro-1,2,4,5-tetraoxanes 2-4 were synthesized as potential peroxide antimalarial drugs. They had curative activity against Plasmodium berghei in vivo at single doses of 320 and 640 mg/kg which confirms earlier unpublished data. Moreover, artemisinin (1) and 4 had equivalent ED50's against P. berghei in vivo in the multiple-dose Thompson test; neither showed any evidence of acute toxicity at total doses of more than 12 g/kg. Dispiro-1,2,4,5-tetraoxane 4 had IC50's comparable to those of 1 against Plasmodium falciparum clones in vitro. These results confirm the potential of dispiro-1,2,4,5-tetraoxanes as a new class of inexpensive peroxide antimalarial drugs. PMID- 1501230 TI - Thieno[2,3-b]furan-2-sulfonamides as topical carbonic anhydrase inhibitors. AB - Novel 5-[(alkylamino)methyl]thieno[2,3-b]furan-2-sulfonamides were prepared and evaluated in vitro for inhibition of human carbonic anhydrase II (CA II) and ex vivo for their ability to inhibit Ca II in the albino rabbit eye after topical administration. Compound 11a was found to lower intraocular pressure (IOP) in both the alpha-CT ocular hypertensive albino rabbit and the normal albino rabbit, but was ineffective at lowering IOP in a hypertensive, pigmented monkey model. Since 11a was highly bound to ocular pigment, a series of less basic analogs was prepared. Examples in this series were both less extensively bound to ocular pigment and more active at reducing IOP in pigmented rabbits after topical dosing. Key examples displayed moderate reactivity toward glutathione. PMID- 1501231 TI - PgH2 analogs as potential antiplatelet derivatives. AB - Previous observations implicating PgH2 as a direct activator of platelets suggested that derivatives of U46619, a well-characterized TxA2 receptor agonist having structural homology with PgH2, might possess antiplatelet activity. The present work describes the synthesis of [1S-(1 alpha,2 beta,3 alpha,4 alpha)]-3 [(tetrahydropyranyloxy)methyl]- 2-[2-[(triphenylmethyl)oxy]ethyl]-5 oxabicyclo[2.2.1]heptane (14) a potentially useful intermediate for the synthesis of various epoxymethano derivatives. The latter was converted to [1S-(1 alpha,2 beta (Z),3 alpha,4 alpha)]-7-[3-[[2- [(phenylamino)carbonyl]-hydrazino]methyl]-5 oxabicylo[2.2.1]hept-2 - yl]-5-heptenoic acid (23), an epoxymethano derivative of PgH2 containing a hydrazide lower side chain as previously used in the TxA2 antagonist, SQ 29,548. The intermediate 14 was also converted to [1S-(1 alpha,2 beta (Z),3 alpha,4 alpha)]-7- [3-[(hexylamino)methyl]-5-oxabicyclo[2.2.1]hept-2 yl]-5-heptenoic acid (25) which contained a simple aza side chain as used in earlier antagonists. Derivatives 23 and 25 appeared to be specific antagonists of the human platelet TxA2 receptor as evidenced by their inhibition of U46619 (1.5 microM) induced aggregation of human platelet rich plasma (IC50 = 22 and 7 microM, respectively), while having little effect on ADP (2 microM) induced aggregation at much higher concentrations. In addition, one of these derivatives, the bicycloamine 25, was shown to compete for [3H]U46619 binding to washed human platelets with an IC50 value of 25 microM, supporting the notion that these derivatives were acting at the thromboxane receptor. However, the potency of these derivatives was less than for previously reported TxA2 antagonists, suggesting that simple linear combinations of functionality from molecules active at the human platelet thromboxane receptor will be of limited predictive value. PMID- 1501232 TI - Improved brain delivery of AZT using a glycosyl phosphotriester prodrug. AB - The concentration of AZT in mice plasma and brain was measured using HPLC after an ingestion of 20 mg/kg of AZT or the molar equivalent of hexadecyl 2-(alpha-D mannopyranosidyl)ethyl 3'-azido-3'-deoxy-5'-thymidinyl phosphate 3. The results demonstrated the promising qualities of the prodrug 3 which gave AZT-5'-phosphate as the main metabolite: the total concentration of AZT derivatives detected in brain presented a peak of 156 nmol/g (5 nmol/g for AZT) at 1 h; the half-life was about 24 h (1 h for AZT) with an AUC of 4366 nmol h/g as compared to 4 nmol h/g for AZT. The lipophilic properties of 3 were confirmed by its in vitro transport of inside synaptosomes. The derivative 2-(alpha-D-mannopyranosidyl)ethyl 3'-azido 3'-deoxy-5'-thymidinyl phosphate (2) provided also a good delivery of AZT to the central nervous system, with values intermediate between those of AZT and 3. PMID- 1501233 TI - 2,3-Epoxy-10-aza-10,11-dihydrosqualene, a high-energy intermediate analogue inhibitor of 2,3-oxidosqualene cyclase. AB - 2,3-Epoxy-10-aza-10,11-dihydrosqualene, a high-energy intermediate analogue inhibitor of 2,3-oxidosqualene (SO) cyclase was obtained by total synthesis. This involved the preparation of three main building blocks: (1) C17 squalenoid N methylamine, (2) 3-(diphenylphosphinoyl)propanal, and (3) 5,6-epoxy-6 methylheptan-2-one. The final stages of the reconstruction of the 6E double bond were obtained by a Wittig-Horner reaction which was modified for poorly reactive systems. This compound was designed to mimic the C-8 carbonium ion formed during SO cyclization. Its inhibitory activity on various SO cyclases was evaluated and compared with the 6 Z isomer which has an unfavorable geometry. Only isomer 6 E, the carbocation analogue, was active on SO cyclases from rat liver, pig liver, S. cerevisiae, and C. albicans microsomes, with an I50 varying from 3 to 5 microM. Both E and Z isomers were inactive on squalene epoxidase at the higher concentrations tested. PMID- 1501234 TI - Adenosine A1 antagonists. 2. Structure-activity relationships on diuretic activities and protective effects against acute renal failure. AB - Diuretic activities of xanthine or nonxanthine adenosine antagonists and their ameliorative effects against glycerol-induced acute renal failure in rats were investigated in order to clarify the physiological and pathological function of adenosine receptors in the kidney. Diuretic and natriuretic activities of a variety of adenosine antagonists clarified systematically for the first time that the blockade of A1 receptors is more important than that of A2 receptors in sodium and water excretion and support the hypothesis that endogenous intrarenal levels of adenosine directly enhance tubular sodium readsorption. Studies of structure-activity relationships of 8-substituted xanthines in the acute renal failure demonstrated that the activation of adenosine A1 receptor was an important factor in developing such a renal failure. A series of 8-(3 noradamantyl)xanthines exhibited the extremely potent diuretic and natriuretic activities (24; 2.5 micrograms/kg, po, the ratio of urinary excretion value in treated rats to urinary excretion value in control rats = 1.69, the ratio of Na+/K+ in treated rats to Na+/K+ in control rats = 1.76) and potent ameliorative effects against glycerol-induced acute renal failure (24; 10 micrograms/kg, ip, 55% inhibition). From our detailed studies of structure-activity relationships, we can speculate that some tissue differences of the adenosine A1 receptor might exist between kidney and brain and sites of action for adenosine antagonists could be different between two renal pharmacological assays. 1,3-Dipropyl-8-(3 noradamantyl)xanthine, KW-3902 (24), was chosen for further studies and is under development as a drug for treating the acute renal failure. PMID- 1501235 TI - Penicillin derived C2-symmetric dimers as novel inhibitors of HIV-1 proteinase. PMID- 1501236 TI - Partial purification of a potassium channel with low permeability for sodium from tonoplast membranes of Hordeum vulgare cv. Gerbel. AB - A potassium-specific tonoplast channel was identified by reconstitution of tonoplast polypeptides into planar lipid bilayer membranes. Highly purified tonoplast membranes were solubilized in Triton X-100-containing buffer and fractionated by size-exclusion chromatography. The protein fractions were assayed for ion channel activity in a planar bilayer system, and the potassium channel was routinely recovered in specific fractions corresponding to an apparent molecular mass of 80 kDa. In symmetrical electrolyte solutions of 100 mM potassium chloride, the potassium channel had a single-channel conductance of 72 pS. Substates of the channel with conductances of 17, 33 and 52 pS were frequently observed. After identification of the channel in low or high KCl, addition of sodium acetate or sodium chloride caused only insignificant conductance changes. This result suggested that the channel was not or little permeable for sodium or chloride, whereas it had similar single-channel conductance for rubidium and caesium ions as compared with potassium ions. The channel is presumably responsible for the equilibration of potassium between the vacuole and the cytosol. The role of the channel in the physiology of the barley cell under salt stress is discussed. PMID- 1501237 TI - Effect of high pH on the plasma membrane potential and conductance in Elodea densa. AB - In leaves of Elodea densa the membrane potential measured in light equals the equilibrium potential of H+ on the morphological upper plasma membrane. The apoplastic pH on the upper side of the leaf is as high as 10.5-11.0, which indicates that alkaline pH induces an increased H+ permeability of the plasmalemma. To study this hypothesis in more detail we investigated the changes in membrane potential and conductance in response to alterations in the external pH from 7 (= control) to 9 or 11 under both light and dark conditions. Departing from the control pH 7 condition, in light and in dark the application of pH 9 resulted in a depolarization of the membrane potential to the Nernst potential of H+. In the light but not in the dark, this depolarization was followed by a repolarization to about -160 mV. The change to pH 9 induced, in light as well as in dark, an increase in membrane conductance. The application of pH 11, which caused a momentary hyper- or depolarization depending on the value at the time pH 11 was applied, brought the membrane potential to around -160 mV. The membrane conductance also increased, in comparison to its value at pH 7, as a result of the application of pH 11, irrespective of the light conditions. PMID- 1501238 TI - Permeation of Ca2+ through K+ channels in the plasma membrane of Vicia faba guard cells. AB - The whole-cell patch-clamp method has been used to measure Ca2+ influx through otherwise K(+)-selective channels in the plasma membrane surrounding protoplasts from guard cells of Vicia faba. These channels are activated by membrane hyperpolarization. The resulting K+ influx contributes to the increase in guard cell turgor which causes stomatal opening during the regulation of leaf-air gas exchange. We find that after opening the K+ channels by hyperpolarization, depolarization of the membrane results in tail current at voltages where there is no electrochemical force to drive K+ inward through the channels. Tail current remains when the reversal potential for permeant ions other than Ca2+ is more negative than or equal to the K+ equilibrium potential (-47 mV), indicating that the current is due to Ca2+ influx through the K+ channels prior to their closure. Decreasing internal [Ca2+] (Cai) from 200 to 2 nM or increasing the external [Ca2+] (Cao) from 1 to 10 mM increases the amplitude of tail current and shifts the observed reversal potential to more positive values. Such increases in the electrochemical force driving Ca2+ influx also decrease the amplitude of time activated current, indicating that Ca2+ permeation is slower than K+ permeation, and so causes a partial block. Increasing Cao also (i) causes a positive shift in the voltage dependence of current, presumably by decreasing the membrane surface potential, and (ii) results in a U-shaped current-voltage relationship with peak inward current ca. -160 mV, indicating that the Ca2+ block is voltage dependent and suggesting that the cation binding site is within the electric field of the membrane. K+ channels in Zea mays guard cells also appear to have a Cai- and Cao dependent ability to mediate Ca2+ influx. We suggest that the inwardly rectifying K+ channels are part of a regulatory mechanism for Cai. Changes in Cao and (associated) changes in Cai regulate a variety of intracellular processes and ion fluxes, including the K+ and anion fluxes associated with stomatal aperture change. PMID- 1501239 TI - Inhibition of Ca-activated K+ channels from renal microvillus membrane vesicles by amiloride analogs. AB - The effect of the K(+)-sparing diuretic amiloride and two of its hydrophobic analogs, methylisobutyl amiloride (MIA) and ethylisopropyl amiloride (EIPA), on Ca-activated K+ channels from renal microvillus membrane vesicles incorporated into planar lipid bilayers was investigated. Amiloride did not inhibit currents through Ca-activated K+ channels. MIA and EIPA, however, inhibited channel currents when added to both the internal and external solutions in concentrations between 10 and 250 microM. Furthermore, when dose-response data for channel inhibition were examined using Hill plots, Hill numbers of approximately 1.5 were found for both blockers from both sides, suggesting that the mechanism of block involves multiple inhibitory binding sites. A simple kinetic scheme is proposed that can account for the results. PMID- 1501240 TI - Transient outwardly rectifying potassium channel in the rabbit corneal endothelium. AB - Ionic currents from freshly dissociated rabbit corneal endothelial cells were examined using patch-clamp technology and a perforated patch technique. Whole cell current recordings revealed a transient outward K(+)-selective current that was blockable in a dose-dependent manner by 4-aminopyridine (4-AP) and quinidine. This current is similar to the 'A'-type current present in many excitable cells and is the first reported instance of such a current in any epithelial cell type. In addition to the transient current, an outwardly rectifying nonselective cation current was also observed. This current is also blocked by quinidine. To examine the possible role of these currents in the stromal volume regulatory function of the endothelium, corneas were perfused under a specular microscope with a glutathione-bicarbonate Ringer's solution (GBR) or GBR plus either 1 mM quinidine or 10 mM 4-AP. For quinidine perfusions, control corneas swelled at a rate of 6 microns/hr, while quinidine-perfused corneas swelled at a rate of 48 microns/hr. For 4-AP perfusions, control corneas swelled at a rate of -2 microns/hr, while 4 AP perfused corneas swelled at a rate of 24 microns/hr. One possible mechanism of the stromal swelling induced by these K+ channel blockers may be the result of loss of the K+ recycling pathway necessary for proper Na+/K+ ATPase function. PMID- 1501241 TI - Flow cytometry and sorting of amphibian bladder endocytic vesicles containing ADH sensitive water channels. AB - The water permeability of ADH target epithelial cells is believed to be regulated by a cycle of exo-endocytosis of vesicles containing functional water channels. These vesicles were selectively labeled in intact frog urinary bladders with an impermeant fluorescent marker, 6-carboxyfluorescein. Vesicle suspensions containing the labeled endosomes were obtained by homogenization and differential centrifugation of bladder epithelial cells. The osmotic permeability of the endocytic vesicles was measured, using a stopped-flow fluorescence technique, in the absence or in the presence of HgCl2. This permeability was found very high (500 microns/sec) and inhibited by 1 mM HgCl2 (90%), thus confirming the presence of water channels. The labeled endosomes were then separated from the other membrane vesicles by flow cytometry and sorting. Their protein content was analyzed by electrophoresis on ultrathin polyacrylamide gels. Two double bands were found at 71 and 55 kDa as well as a small band at 43 kDa. They respectively correspond to 31, 38 and 10% of the total amount of silver-stained proteins present in the sorted endosomes, while they only represent 2, 4, and less than 1% of the proteins contained in the vesicle suspension, before sorting. These highly enriched proteins (or at least one of them) are likely to be involved in the mechanism of water transport. Associated to their partial purification by differential centrifugation, the sorting of the endosomes by flow cytometry seems a good way to further characterize the water channel. PMID- 1501242 TI - Interaction of eosinophil granule major basic protein with synthetic lipid bilayers: a mechanism for toxicity. AB - Eosinophil granule major basic protein (MBP) is a potent toxin for mammalian cells and helminths, but the mechanism of its toxicity is not known. Here we tested whether MBP toxicity is exerted through its effect on the lipid bilayer of its targets. Liposomes prepared from synthetic phospholipids were used as targets for MBP and their properties examined by fluorescence and circular dichroism (CD) spectroscopy. MBP caused a change in the temperature transition profiles of acidic liposomes (1-palmitoyl-2-oleoyl-sn-glycero-3-phosphatidyl serine or an equimolar mixture of 1,2-dimyristoyl-sn-glycero-3-phosphocholine and 1,2 dimyristoyl-sn-glycero-3-phosphatidic acid) and induced their aggregation as shown by fluorescence resonance energy transfer experiments. The CD spectra and fluorescence characteristics of MBP itself were altered by its interaction with acidic lipids. Blue shifts in the emission maxima of the Trp, and of the dimethylaminonaphthyl moiety in acrylodan-labeled MBP, and a reduction in the effectiveness of quenching of Trp fluorescence by acrylamide were observed in the presence of acidic lipids. None of these effects were noted with zwitterionic lipids. This MBP: lipid bilayer interaction resulted in fusion and lysis of liposomes as indicated by the fluorescent indicator calcein. The results demonstrate that MBP associates with acidic lipids and that it disrupts, aggregates, fuses, and lyses liposomes prepared from such lipids. Such interaction might account for its wide range of toxicity. PMID- 1501244 TI - Single-membrane and cell-to-cell permeability properties of dissociated embryonic chick lens cells. AB - Ion channels are believed to play an important role in the maintenance of lens transparency. In order to ascribe junctional and nonjunctional permeability properties to specific lens cell types, embryonic chick lenses were enzymatically dissociated into cell clusters, cell pairs and single cells, and both cell-to cell and single-membrane permeability properties were characterized with the patch-clamp technique. Double patch-clamp experiments and single patch-clamp experiments with Lucifer yellow in the pipette demonstrated that the cells in the dissociated preparation were well coupled, the average conductance between pairs being 42 +/- 27 nS. Double patch-clamp experiments also revealed single cell-to cell channel events with a predominant unitary conductance of 286 +/- 38 pS. Whole-cell measurements of surface membrane conductance indicate heterogeneity within the population of dissociated embryonic chick lens cells: 63% of the cells have a voltage-independent leak current, 14% of the cells have a potassium selective inward-rectifier current, and 23% of the cells have a current which turns off with positive voltage on a time scale on the order of seconds. The time constant for this turnoff is voltage dependent. PMID- 1501243 TI - Epidermal growth factor receptor: elements of intracellular communication. AB - While EGF has an important function in cell growth regulation, the molecular mechanisms by which intracellular signal connect the EGF: receptor complex on the plasma membrane with the initiation of DNA synthesis and mitogenesis is not well understood. The discovery that rasGAP, PI-3 kinase and PLC-gamma 1 are substrates for the EGF receptor tyrosine kinase has provided a beginning in understanding the biochemistry underlying growth factor receptor transduction. PMID- 1501245 TI - Depolarization-induced calcium release from isolated triads measured with impermeant fura-2. AB - Depolarization-induced Ca2+ release was studied in a mixture of triads and terminal cisternae isolated from rabbit skeletal muscle. The vesicles were actively loaded with known amounts of Ca2+ in the absence of precipitating anions in a solution containing 100 mM K propionate buffer. Changes in extravesicular Ca2+ were monitored with 10 microM Fura-2 (membrane impermeant form). Ca2+ release was initiated by diluting an aliquot of the loaded vesicles into a TEACl release solution designed to maintain a constant [K+].[Cl-] product. Fast release, defined as the percentage of total Ca2+ loaded which released in less than 10 sec, occurred when extravesicular free Ca2+ was in the submicromolar range and was unaffected by 5 mM caffeine under depolarizing conditions, change in external pH to 6.5, and an increase in external Mg2+ concentration from 0.1 to 0.2 mM. Thus, the Ca2+ release measured in these studies is distinct from Ca(2+) induced Ca2+ release. The fast release more than doubled when a greater dilution (1:20 versus 1:10) of the loaded vesicles into the release solution, which would produce a larger depolarization, was used. The percentage of loaded Ca2+ which released rapidly in a particular triad preparation was similar to the percentage of vesicles structurally coupled as visualized by electron microscopy. PMID- 1501246 TI - Transport and membrane binding of the glutamine analogue 6-diazo-5-oxo-L norleucine (DON) in Xenopus laevis oocytes. AB - We have examined transport and membrane binding of 6-diazo-5-oxo-L-norleucine (DON, a photoactive diazo-analogue of glutamine) and their relationships to glutamine transport in Xenopus laevis oocytes. DON uptake was stereospecific and saturable (Vmax of 0.44 pmol/oocyte.min and a Km of 0.065 mM). DON uptake was largely Na+ dependent (80% at 50 microM DON) and inhibited (greater than 75%) by glutamine and arginine (substrates of the System B0,+ transporter) at 1 mM. Glutamine and DON show mutual competitive inhibition of Na(+)-dependent transport. Preincubation of oocytes in medium containing 0.1 mM DON for 24 or 48 hr depressed the Vmax for System B0,+ transport (as measured by Na(+)-dependent glutamine uptake), this effect was highly specific (neither D-DON nor the System B0,+ substrates glutamine and D-alanine showed any independent effect) and required Na+ ions. Glutamine (1 mM in preincubation medium) protected transport from inhibition by DON. The possibility that specific inactivation of System B0,+ by DON reflects attachment of DON to the transporter was tested by examining the binding of [14C]DON to Xenopus oocyte membranes. Oocytes incubated in 100 mM NaCl in the presence of [14C]DON for up to 48 hr showed 2.4-fold higher 14C-binding to membranes than oocytes incubated in choline chloride. Na(+)-dependent DON binding (31 +/- 11 fmol/micrograms membrane protein) was suppressed by external glutamine, arginine or alanine and was largely confined to a membrane protein fraction of 48-65 kDa (as assessed by SDS-polyacrylamide gel electrophoresis). The present studies indicate that DON and glutamine uptake in oocytes are both mediated by System B0,+ and demonstrate the DON binding to a particular membrane protein fraction is associated with inactivation of the transporter, offering the prospect of using [14C]DON as a covalent label for the transport protein in order to facilitate its isolation and subsequent biochemical characterization. PMID- 1501247 TI - On coenzyme Q orientation in membranes: a linear dichroism study of ubiquinones in a model bilayer. AB - A general approach is developed to interpret linear dichroism (LD) spectra of ubiquinones (Qn) in host bilayers. Information is reported in terms of guest-host mutual orientation and localization. The overall orientational anisotropy of guest ubiquinone molecules is described by a basic set of limiting orientation/localization modes. Assignments of the UV transitions of the ubiquinone chromophore were obtained by the liquid crystal-linear dichroism technique and molecular orbital (CNDO/S) calculations. The LD spectra of Qn in the bilayers provided by the lyotropic nematic mesophase exhibited by water solutions of potassium laurate and decanol were interpreted on the basis of the above assignments. The resulting experimental evidence showed a multisite distribution in the host bilayer for the aromatic heads of all the investigated Qn derivatives except Q0. The orientational distribution suggested by the LD spectra fits the solubilization model recently proposed by G. Lenaz [J. Membrane Biol. (1988) 104:193-209] for ubiquinone in lipid membranes. Within this model Qn molecules are located in the midplane and their headgroups oscillate transversally across the membrane. Q0 instead has a single site location, close to the polar bilayer interface. Experimental evidence that the headgroup carbonyls tend to grasp the polar interface of the host bilayer was also obtained. Orientation and location distributions of Qn guest molecules are therefore likely to result from the tendency of their aromatic heads to grasp the polar heads of the host bilayer and from the concurrent tendency of their chains to settle into the hydrocarbon host interior. PMID- 1501248 TI - Uridine transport in basolateral plasma membrane vesicles from rat liver. AB - The characteristics of uridine transport were studied in basolateral plasma membrane vesicles isolated from rat liver. Uridine was not metabolized under transport measurements conditions and was taken up into an osmotically active space with no significant binding of uridine to the membrane vesicles. Uridine uptake was sodium dependent, showing no significant stimulation by other monovalent cations. Kinetic analysis of the sodium-dependent component showed a single system with Michaelis-Menten kinetics. Parameter values were KM 8.9 microM and Vmax 0.57 pmol/mg prot/sec. Uridine transport proved to be electrogenic, since, firstly, the Hill plot of the kinetic data suggested a 1 uridine: 1 Na+ stoichiometry, secondly, valinomycin enhanced basal uridine uptake rats and, thirdly, the permeant nature of the Na+ counterions determined uridine, transport rates (SCN- greater than NO3- greater than Cl- greater than SO4(2-)). Other purines and pyrimidines cis-inhibited and trans-stimulated uridine uptake. PMID- 1501249 TI - Management of the refractory endodontic infection. PMID- 1501250 TI - Molecules, fossils, and the origin of tetrapods. AB - Since the discovery of the coelacanth, Latimeria chalumnae, more than 50 years ago, paleontologists and comparative morphologists have debated whether coelacanths or lungfishes, two groups of lobe-finned fishes, are the closest living relatives of land vertebrates (Tetrapoda). Previously, Meyer and Wilson (1990) determined partial DNA sequences from two conservative mitochondrial genes and found support for a close relationship of lungfishes to tetrapods. We present additional DNA sequences from the 12S rRNA mitochondrial gene for three species of the two lineages of lungfishes that were not represented in the first study: Protopterus annectens and Protopterus aethiopicus from Africa and Neoceratodus forsteri (kindly provided by B. Hedges and L. Maxson) from Australia. This extended data set tends to group the two lepidosirenid lungfish lineages (Lepidosiren and Protopterus) with Neoceratodus as their sister group. All lungfishes seem to be more closely related to tetrapods than the coelacanth is. This result appears to rule out the possibility that the coelacanth lineage gave rise to land vertebrates. The common ancestor of lungfishes and tetrapods might have possessed multiple morphological traits that are shared by lungfishes and tetrapods [Meyer and Wilson (1990) listed 14 such traits]. Those traits that seem to link Latimeria and tetrapods are arguably due to convergent evolution or reversals and not to common descent. In this way, the molecular tree facilitates an evolutionary interpretation of the morphological differences among the living forms. We recommended that the extinct groups of lobe-finned fishes be placed onto the molecular tree that has lungfishes and not the coelacanth more closely related to tetrapods. The placement of fossils would help to further interpret the sequence of morphological events and innovations associated with the origin of tetrapods but appears to be problematic because the quality of fossils is not always high enough, and differences among paleontologists in the interpretation of the fossils have stood in the way of a consensus opinion for the branching order among lobefinned fishes. Marshall and Schultze (1992) criticized the morphological analysis presented by Meyer and Wilson (1990) and suggest that 13 of the 14 morphological traits that support the sister group relationship of lungfishes and tetrapods are not shared derived characters. Here we present further alternative viewpoints to the ones of Marshall and Schultze (1992) from the paleontological literature. We argue that all available information (paleontological, neontological, and molecular data) and rigorous cladistic methodology should be used when relating fossils and extant taxa in a phylogenetic framework. PMID- 1501251 TI - Telomere-associated repeats in Chironomus form discrete subfamilies generated by gene conversion. AB - In dipteran insects the most distal telomere-associated DNA known to exist consists of long, complex tandem repeats. We have classified the 340-bp tandemly arranged repeats in Chironomus pallidivittatus. The repeats are distributed in a small number of subfamilies. One type of the repeat has the character of a master unit from which other main units can be derived usually by simple changes. The derived subfamilies contain segments that are degenerate versions of the corresponding segment in the master sequence. Such segments can also occur together in one and the same repeat unit in different combinations. There is a complete absence of subfamily-specific base variants in regions lying outside of the degenerate segments. Homogenization takes place between DNA sequences that are often smaller than a whole repeat unit. The mosaic structure of the repeat arrays suggests that gene conversion is an important force in the generation and maintenance of this family of repeats. PMID- 1501252 TI - Essential role of duplications of short motif sequences in the genomic evolution of Bombyx mori. AB - The Bombyx fibroin gene has a discrete mosaic structure of various repetitive sequences, which may have evolved through various repeating arrangements. Detailed sequence analysis of the fibroin gene containing coding and noncoding regions revealed that the whole sequence could be arranged as an array of short repetitive sequences. A portion of the intron of the fibroin gene is one of interspersed repetitive elements. We cloned a 1.5-kb DNA fragment of the Bombyx genome that contains interspersed elements homologous to the intron sequence. Sequence comparison between the intron and the 1.5-kb fragment shows that partial duplication has frequently occurred in evolutionary progress, and the resultant repetitive blocks of short motif sequences are abundant in the genome. These facts suggest that tandem duplication of the short motif sequence is an important rearrangement in genomic evolution of the fibroin gene. PMID- 1501253 TI - A nematode hemoglobin gene contains an intron previously thought to be unique to plants. AB - Hemoglobin genes from plants and animals both have a characteristic chromosomal organization. Plant hemoglobin genes contains a unique intron inserted into the heme-binding domain of exon 2. This intron has not been previously reported in animal globin genes, and its loss was hypothesized to have occurred early in the evolution of hemoglobins. We report here a unique six-intron, seven-exon internally duplicated nematode hemoglobin gene that contains an intron equivalent to the plant central intron in its first repeat. This nematode hemoglobin gene has lost both the central and the normal third intron in its second repeat. The nematode globin also contains a unique intron between its secretory peptide leader sequence and its coding sequence, which is absent in other extracellular invertebrate globin genes. Possible models to explain the head-to-tail duplication of this gene are discussed. PMID- 1501254 TI - Evolutionary relationships of multiple alpha satellite subfamilies in the centromeres of human chromosomes 13, 14, and 21. AB - Using Southern and in situ hybridization analyses, we have earlier defined four different subfamilies of alpha satellite DNA (designated pTRA-1, -2, -4, and -7), each of which has a unique higher order structure represented almost identically on human chromosomes 13, 14, and 21. Here we present the complete sequence of single isolates of these four subfamilies, representing approximately 12 kb of sequence information. Sequences of the individual 171-bp monomers that constitute these four subfamilies (and a fifth subfamily, Alpha-R1, that is known to be present on chromosomes 13 and 21) were compared both within and between the different clones. The results indicate that, at the level of their primary sequence, the five alpha subfamilies are characterized by structures that are as unrelated to each other as the different alpha subfamilies from other chromosomes. However, sequence comparisons between monomers of these clones indicate the possibility that pTRA-2, -4, and -1 may have arisen, at least in part, from a common ancestral alphoid sequence. We also provide evidence that exchange of pTRA-1 between nonhomologous centromeres and its homogenization throughout the population, perhaps by unequal exchange mechanisms, could have occurred after the divergence of humans and chimpanzees. The evolution of multiple alphoid subfamilies within a single centromere suggests that unequal exchange mechanisms may be restricted to specific domains. This may in turn contribute to some requirement for subregional pairing of sequences along the length of the centromeres of these chromosomes. PMID- 1501256 TI - Interchromosomal gene conversion as a possible mechanism for explaining divergence patterns of ZFY-related genes. AB - The divergence pattern of mammalian ZFY-related genes from human (ZFY and ZFX) and mouse (Zfy-1 and Zfx) was reexamined on the basis of nucleotide substitutions at the synonymous codon-alternating positions. It is possible to explain the unusual divergence pattern of the mammalian Y-linked ZF genes by interchromosomal gene conversion by X-linked ZF genes. Furthermore, the rates of evolution of mammalian X- and Y-linked ZF genes were shown to agree well with those expected from our model. PMID- 1501257 TI - Relative importance of molecular, neontological, and paleontological data in understanding the biology of the vertebrate invasion of land. AB - Meyer and Wilson's (1990) 12S rRNA phylogeny unites lungfish and tetrapods to the exclusion of the coelacanth. These workers also provide a list of morphological features shared in common between modern lungfish and tetrapods, and they conclude that these traits were probably present in their last common ancestor. However, the exquisite fossil records of the abundant extinct lungfishes and rhipidistians show that at least 13 out of Meyer and Wilson's 14 supposed ancestral traits were not present in the last common ancestor of lungfishes and tetrapods. Using extant taxa to infer ancestral morphologies is fraught with difficulties; just like molecular sequences, ancestral character states of morphological traits may be severely overprinted by subsequent modifications. Modern lungfish are air-breathing nonmarine forms, yet their Devonian forebears were marine fish that did not breathe air. Fossils dating from the time of origin of tetrapods in the Devonian offer the only hope of understanding the morphological innovations that led to tetrapods; morphological analysis of the "living fossils," the coelacanth and lungfish, only lends confusion. PMID- 1501258 TI - The right to know. PMID- 1501259 TI - Ophthalmic manifestations of the acquired immunodeficiency syndrome. AB - 1. Ophthalmic manifestations of AIDS involve both anterior and posterior segments and can result in total loss of vision. Understanding of these ocular manifestations has become more important as this disease continues to proliferate. 2. Although the risk of infection by HIV in the ophthalmic setting is remote, ophthalmic health-care workers may come in contact with potentially infectious fluids in the course of normal ocular examination procedures. Infection control procedures are therefore recommended. 3. If health-care workers experience a possible exposure, they should consult a physician specializing in infectious diseases or internal medicine within 1 hour. Individuals should be evaluated for hepatitis B and tetanus, and considered for zidovudine chemoprophylaxis, in addition to being tested for HIV exposure. PMID- 1501260 TI - Perfluorocarbon liquid in the management of complex retinal detachments. AB - 1. Conventional techniques of pars plana vitrectomy, retinal membrane stripping, scleral buckling, fluid-air or fluid-gas exchange, and silicone oil injection are ineffective in 25% of the complex retinal detachments reported. 2. The properties of perfluorocarbon liquid--clear, water immiscible, specific gravity twice that of water--make it an important adjunct to treatment of complex retinal detachments. 3. Of great interest is the fact that research has shown that visual outcome is significantly better for eyes using perfluorocarbon to initially flatten the retina. PMID- 1501261 TI - Color vision testing. AB - 1. Color deficiency occurs in about 8% of the population, due to alterations in the chemistry of one of the three receptive pigments for colored light, or the substitution of one pigment for another in the photoreceptor cones. 2. Subjects with pigment alteration can see a broad range of color; those with substitution of one pigment for another have broad areas of color perception defect. 3. The most common tests are pseudoisochromatic (color confusion) plates, designed with patterns hidden to the color deficient. Other tests use colored caps, tracing patterns, or an anomaloscope. PMID- 1501262 TI - Brown iris lesions in both eyes: iris flocculi. PMID- 1501263 TI - Innovative uses for disposable lenses. PMID- 1501255 TI - Evolutionary consequences of nonrandom damage and repair of chromatin domains. AB - Some evolutionary consequences of different rates and trends in DNA damage and repair are explained. Different types of DNA damaging agents cause nonrandom lesions along the DNA. The type of DNA sequence motifs to be preferentially attacked depends upon the chemical or physical nature of the assaulting agent and the DNA base composition. Higher-order chromatin structure, the nonrandom nucleosome positioning along the DNA, the absence of nucleosomes from the promoter regions of active genes, curved DNA, the presence of sequence-specific binding proteins, and the torsional strain on the DNA induced by an increased transcriptional activity all are expected to affect rates of damage of individual genes. Furthermore, potential Z-DNA, H-DNA, slippage, and cruciform structures in the regulatory region of some genes or in other genomic loci induced by torsional strain on the DNA are more prone to modification by genotoxic agents. A specific actively transcribed gene may be preferentially damaged over nontranscribed genes only in specific cell types that maintain this gene in active chromatin fractions because of (1) its decondensed chromatin structure, (2) torsional strain in its DNA, (3) absence of nucleosomes from its regulatory region, and (4) altered nucleosome structure in its coding sequence due to the presence of modified histones and HMG proteins. The situation in this regard of germ cell lineages is, of course, the only one to intervene in evolution. Most lesions in DNA such as those caused by UV or DNA alkylating agents tend to diminish the GC content of genomes. Thus, DNA sequences not bound by selective constraints, such as pseudogenes, will show an increase in their AT content during evolution as evidenced by experimental observations. On the other hand, transcriptionally active parts may be repaired at rates higher than inactive parts of the genome, and proliferating cells may display higher repair activities than quiescent cells. This might arise from a tight coupling of the repair process with both transcription and replication, all these processes taking place on the nuclear matrix. Repair activities differ greatly among species, and there is a good correlation between life span and repair among mammals. It is predicted that genes that are transcriptionally active in germ-cell lineages have a lower mutation rate than bulk DNA, a circumstance that is expected to be reflected in evolution. Exception to this rule might be genes containing potential Z-DNA, H DNA, or cruciform structures in their coding or regulatory regions that appear to be refractory to repair.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1501264 TI - Radiographic manifestations of thoracic involvement by collagen vascular diseases. AB - Collagen vascular diseases (CVDs) are a group of immunologic diseases that affect connective tissue at various locations throughout the body. The article reviews the variable radiographic findings associated with the common and less common CVDs. PMID- 1501265 TI - High-resolution computed tomography scanning in the assessment of interstitial lung diseases. AB - The development of high-resolution computed tomography (HRCT) has added a new dimension to the radiographic evaluation of interstitial lung diseases. The article reviews the techniques for HRCT, the normal anatomy seen by HRCT, and the HRCT findings of interstitial lung diseases. PMID- 1501266 TI - Bronchoalveolar lavage in patients with connective tissue disease. AB - Bronchoalveolar lavage (BAL) allows the recovery of cellular and fluid constituents that are derived from the epithelial surface of the lower respiratory tract. BAL fluid and cell analysis has become an important tool for understanding human pulmonary disease. Changes in the quantities and patterns of BAL cells and secretions have been described in a number of chronic lung disorders, especially the diffuse interstitial lung diseases. Specific BAL alterations have correlated with patient outcome and response to therapy. The connective tissue diseases have been associated with serious pleural and/or pulmonary pathology and may be a major cause of morbidity and mortality. BAL appears to be a useful semi-invasive tool in the evaluation and management of lung disease in patients with connective tissue diseases. The article describes the BAL findings in various connective tissue diseases and assesses the usefulness of BAL in the clinical management of patients with pulmonary complications. PMID- 1501267 TI - Cardiovascular manifestations of connective tissue disorders. AB - Disease processes that involve abnormalities of the connective tissue are protean in their manifestations because of the ubiquitous and crucial function that connective tissue serves in the body. Connective tissue supports of the heart and vascular structures play an integral role in normal cardiovascular performance, and it is not surprising that many connective tissue disorders produce important pathophysiologic processes that affect cardiac and vascular elements. The article focuses on the cardiac and vascular manifestations of hereditary and acquired forms of connective tissue disease. Special attention is focused on the use of imaging modalities and their role in diagnosing cardiovascular pathology produced by collagen disorders. PMID- 1501268 TI - Thin-rim enhancement in Gd-DTPA-enhanced magnetic resonance images of tuberculoma: a new finding of potential differential diagnostic importance. AB - The article describes rim enhancement seen on Gd-DTPA-enhanced magnetic resonance (MR) images of two patients with tuberculoma. Pathologic examination of the surgical specimens disclosed that the peripheral portion of the tuberculoma, which showed contrast enhancement, was composed mainly of a fibrous capsule and epithelioid granulomas and that the central zone, which showed no contrast enhancement, was composed of caseous necrotic material. In a retrospective study of MR images from 20 consecutive cases of surgically proven bronchogenic carcinoma, none showed a thin enhancing rim on postcontrast MR images. Although confirmation of these findings must await further experience, the postcontrast MR findings described here may prove to be of value in distinguishing tuberculoma and possibly other granulomatous lesions from bronchogenic carcinoma. PMID- 1501269 TI - Intrapulmonary teratoma: a case report and review of the literature. AB - Intrapulmonary teratomas are rare; only 30 cases have been reported in the world literature. These tumors are thought to originate from the third pharyngeal pouch. They occur equally in men and women and usually are diagnosed in the second to fourth decade of life. They are more often benign than malignant, although malignant lesions may have a favorable postoperative prognosis and benign lesions may exhibit high morbidity and mortality because of their size and location. These tumors present radiographically as lobulated masses that may contain calcification or peripheral collections of air. They most often occur in the upper lobes. The computed tomographic findings of intrapulmonary teratoma are less well known but have been described in two cases. An additional case is presented with a review of the literature and a tabular summary of the characteristics of this unusual entity. PMID- 1501270 TI - Traumatic mediastinal lymphocele mimicking other thoracic injuries: case report. AB - Thoracic duct injury and chylothorax are rare consequences of blunt thoracic trauma. A contained mediastinal lymph collection (ie, lymphocele) is rarer still. The article describes a case of posttraumatic mediastinal widening resulting from a high-speed motor vehicle accident. During the patient's radiologic assessment aortic rupture, paraspinal hematoma, esophageal injury, mediastinal tumor, and pseudomeningocele were sought and subsequently excluded. At this point a traumatic lymphocele was suggested, and the diagnosis was confirmed by computed tomography-guided percutaneous needle aspiration. The anatomy and physiology of the thoracic duct are reviewed. PMID- 1501271 TI - Second-site suppressor mutations assist in studying the function of the 3' noncoding region of turnip yellow mosaic virus RNA. AB - The 3' noncoding region of turnip yellow mosaic virus RNA includes an 82 nucleotide-long tRNA-like structure domain and a short upstream region that includes a potential pseudoknot overlapping the coat protein termination codon. Genomic RNAs with point mutations in the 3' noncoding region that result in poor replication in protoplasts and no systemic symptoms in planta were inoculated onto Chinese cabbage plants in an effort to obtain second-site suppressor mutations. Putative second-site suppressor mutations were identified by RNase protection and sequencing and were then introduced into genomic cDNA clones to permit their characterization. A C-57----U mutation in the tRNA-like structure was a strong suppressor of the C-55----A mutation which prevented both systemic infection and in vitro valylation of the viral RNA. Both of these phenotypes were rescued in the double mutant. An A-107----C mutation was a strong second-site suppressor of the U-96----G mutation, permitting the double mutant to establish systemic infection. The C-107 and G-96 mutations are located on opposite strands of one helix of a potential pseudoknot, and the results support a functional role for the pseudoknot structure. A mutation near the 5' end of the genome (G + 92--- A), at position -3 relative to the initiation codon of the essential open reading frame 206, was found to be a general potentiator of viral replication, probably as a result of enhanced expression of open reading frame 206. The A + 92 mutation enhanced the replication of mutant TYMC-G96 in protoplasts but was not a sufficiently potent suppressor to permit systemic spread of the A + 92/G-96 double mutant in plants. PMID- 1501272 TI - Nuclear factors that bind two regions important to transcriptional activity of the simian immunodeficiency virus long terminal repeat. AB - Previous studies identified two regions in the U3 region of a molecular clone of simian immunodeficiency virus, SIVmac142, that are important to transcriptional activity under conditions of induction as well as basal-level expression (B. Renjifo, N. A. Speck, S. Winandy, N. Hopkins, and Y. Li, J. Virol. 64:3130-3134, 1990). One region includes the NF-kappa B binding site, while the other lies just 5' of this site between nucleotides -162 and -114 (the -162 to -114 region). The fact that the NF-kappa B site mutation attenuated transcriptional activity in uninduced T cells and fibroblasts where activated NF-kappa B would not be present suggested that a factor(s) other than NF-kappa B could be acting through this site. In this study, we have identified a factor which binds to a cis element overlapping the NF-kappa B site. This factor, which we call simian factor 3 (SF3), would play a role in regulation under conditions of basal level expression, whereas under conditions of induction, NF-kappa B would act via this region. SF3 may also bind to an element in the -162 to -114 region. In addition, we have identified two other factors that bind the -162 to -114 region. One, which we designated SF1, is a ubiquitous basal factor, and the other, SF2, is a T cell-predominant phorbol myristate acetate-inducible factor. Through identification of nuclear factors that interact with the U3 region of the SIVmac142 long terminal repeat, we can gain insight into how this virus is transcriptionally regulated under conditions of basal-level expression as well as conditions of T-cell activation. PMID- 1501273 TI - RNA- and DNA-binding activities in hepatitis B virus capsid protein: a model for their roles in viral replication. AB - The hepatitis B virus capsid or core protein (p21.5) binds nucleic acid through a carboxy-terminal protamine region that contains nucleic acid-binding motifs organized into four repeats (I to IV). Using carboxy-terminally truncated proteins expressed in Escherichia coli, we detected both RNA- and DNA-binding activities within the repeats. RNA-binding and packaging activity, assessed by resolving purified E. coli capsids on agarose gels and disclosing their RNA content with ethidium bromide, required only the proximal repeat I (RRRDRGRS). Strikingly, a mutant in which four Arg residues replaced repeat I was competent to package RNA, demonstrating that Arg residues drive RNA binding. In contrast, probing immobilized core proteins with 32P-nucleic acid revealed an activity which (i) required more of the protamine region (repeats I and II), (ii) appeared to bind DNA better than RNA, and (iii) was apparently modulated by phosphorylation in p21.5 derived from Xenopus oocytes. Deletion analysis suggested that this activity may depend on an SPXX-type DNA-binding motif in repeat II. Similar motifs found in repeats III and IV may also function to bind DNA. On the basis of these observations, together with a reinterpretation of recent studies showing that capsid protein mutants cause defects in viral genome replication, we propose a model suggesting that hepadnavirus capsid proteins participate directly in the intracapsid reverse transcription of RNA into DNA. In this model, repeat I binds RNA whereas the distal repeats are progressively recruited to bind elongating DNA strands. The latter motifs may be required for replication to be energetically feasible. PMID- 1501274 TI - Human immunodeficiency virus type 1 nef quasispecies in pathological tissue. AB - The role of the nef gene in human immunodeficiency virus type 1 (HIV-1) infection is poorly understood. To provide a basis for studies on the role of nef in AIDS, we used targeted polymerase chain reaction amplification and DNA sequencing to determine the structure of nef genes in pathologic tissue from HIV-1-infected children and adults. We find that the nef reading frame is open in 92% of clones derived from both brain and lymphocytic tissue of children, suggesting that nef is expressed in these tissues. One HIV-1 clone, BRVA, obtained by coculture from the brain of an adult AIDS patient with progressive dementia, was previously shown to contain a duplicated region in nef. We show here that similar duplications are widespread in both adults and children with AIDS. However, coculture strongly selects against the broad spectrum of nef quasispecies found in tissue. These findings suggest functional selection for nef quasispecies in pathologic tissues during HIV-1 infection of the human host. PMID- 1501275 TI - The nucleocapsid protein gene of bovine coronavirus is bicistronic. AB - For animal RNA viruses that replicate through an RNA intermediate, reported examples of bicistronic mRNAs with overlapping open reading frames in which one cistron is contained entirely within another have been made only for those with negative-strand or double-stranded genomes. In this report, we demonstrate for the positive-strand bovine coronavirus that an overlapping open reading frame potentially encoding a 23-kDa protein (names the I [for internal open reading frame] protein) and lying entirely within the gene for the 49-kDa nucleocapsid phosphoprotein is expressed during virus replication from a single species of unedited mRNA. The I protein was specifically immunoprecipitated from virus infected cells with an I-specific antipeptide serum and was shown to be membrane associated. Many features of I protein synthesis conform to the leaky ribosomal scanning model for regulation of translation. This, to our knowledge, is the first example of a bicistronic mRNA for a cytoplasmically replicating, positive strand animal RNA virus in which one cistron entirely overlaps another. PMID- 1501276 TI - Moloney murine sarcoma virus MuSVts110 DNA: cloning, nucleotide sequence, and gene expression. AB - We have cloned Moloney murine sarcoma virus (MuSV) MuSVts110 DNA by assembly of polymerase chain reaction (PCR)-amplified segments of integrated viral DNA from infected NRK cells (6m2 cells) and determined its complete sequence. Previously, by direct sequencing of MuSVts110 RNA transcribed in 6m2 cells, we established that the thermosensitive RNA splicing phenotype uniquely characteristic of MuSVts110 results from a deletion of 1,487 nucleotides of progenitor MuSV-124 sequences. As anticipated, the sequence obtained in this study contained precisely this same deletion. In addition, several other unexpected sequence differences were found between MuSVts110 and MuSV-124. For example, in the noncoding region upstream of the gag gene, MuSVts110 DNA contained a 52 nucleotide tract typical of murine leukemia virus rather than MuSV-124, suggesting that MuSVts110 originated as a MuSV-helper murine leukemia virus recombinant during reverse transcription rather than from a straightforward deletion within MuSV-124. In addition, both MuSVts110 long terminal repeats contained head-to-tail duplications of eight nucleotides in the U3 region. Finally, seven single-nucleotide substitutions were found scattered throughout MuSVts110 DNA. Three of the nucleotide substitutions were in the gag gene, resulting in one coding change in p15 and one in p30. All of the remaining nucleotide changes were found in the noncoding region between the 5' long terminal repeat and the gag gene. In NIH 3T3 cells transfected with the cloned MuSVts110 DNA, the pattern of viral RNA expression conformed with that observed in cells infected with authentic MuSVts110 virus in that viral RNA splicing was 30 to 40% efficient at growth temperatures between 28 and 33 degrees C but reduced to trace levels above 37 degrees C. PMID- 1501277 TI - A cysteine and a hydrophobic sequence in the noncleaved portion of the pre-C leader peptide determine the biophysical properties of the secretory core protein (HBe protein) of human hepatitis B virus. AB - The molecular basis of the biophysical and antigenic differences between the cellular core protein (HBc protein) and the secreted core protein (HBe protein) of human hepatitis B virus was examined. The data show that the properties which distinguish the HBe protein from the HBc protein are due mostly to the 10-amino acid portion of the HBe leader sequence which remains attached to the HBe protein after cleavage. A cysteine located within this region determines the quaternary structure and the antigenicity of the HBe protein. If this cysteine is lacking, the HBe protein, which is predominantly a monomer with only HBe antigenicity, is expressed as a disulfide-linked homodimer showing both HBe and HBc antigenicity. However, dimerization of the HBe protein was found to be neither sufficient nor required for particle formation. In fact, aggregation of the HBe protein was found to be inhibited by the strongly hydrophobic tripeptide Trp-Leu-Trp, which is also located in the noncleaved portion of the signal sequence. If this tripeptide was converted into either Asp-Asn-Asn or Ala-Asp-Leu, the HBe protein assembled into particles, independent of the presence of the cysteine. PMID- 1501278 TI - Proteolytic cleavage of the reovirus sigma 3 protein results in enhanced double stranded RNA-binding activity: identification of a repeated basic amino acid motif within the C-terminal binding region. AB - The reovirus capsid protein sigma 3 was examined for double-stranded RNA (dsRNA) binding activity by Northwestern (RNA-protein) blot analysis. Treatment of virion derived sigma 3 protein with Staphylococcus aureus V8 protease led to an increase in the dsRNA-binding activity associated with the C-terminal fragment of the protein. Recombinant C-terminal fragments of the sigma 3 protein were expressed in Escherichia coli from the S4 cDNA of reovirus serotype 1. These truncated sigma 3 proteins displayed proteolytic processing and dsRNA-binding activity similar to those observed for native, virion-derived sigma 3 protein as measured by Northwestern blot analysis. Construction of a modified pET3c vector, pET3Exo, allowed the production of 3'-terminal deletions of the S4 cDNA by using exonuclease III and rapid screening of the induced truncated sigma 3 proteins. An 85-amino-acid domain within the C-terminal portion of the sigma 3 protein which was responsible for dsRNA-binding activity was identified. The 85-amino-acid domain possessed a repeated basic amino acid motif which was conserved in all three serotypes of reovirus. Deletion of one of the basic motifs, predicted to be an amphipathic alpha-helix, destroyed dsRNA-binding activity. PMID- 1501279 TI - Vaccinia virus infection induces a stress response that leads to association of Hsp70 with viral proteins. AB - We studied the impact of vaccinia virus infection on stress protein gene expression in human cells and investigated the possibility that eukaryotic heat shock proteins interact with viral components during assembly. Infection of human monocyte-macrophages by vaccinia virus caused a dramatic decrease in levels of cellular mRNAs such as those encoding actin and tubulin. In contrast, infection did not cause a significant reduction in the levels of Hsp90 and Hsp60 mRNAs and led to substantially increased levels of Hsp70 mRNAs. The accumulation of these stress protein mRNAs was due both to increases in their transcription rate and to their stability relative to other cellular mRNAs. The relative levels of the heat shock proteins and the other cellular proteins reflected the relative levels of their mRNAs. These results indicate that stress protein gene expression is relatively refractory to the generally deleterious effects of vaccinia virus infection on host cell gene expression. The continued expression of some of these stress proteins may be beneficial to the virus; the observations that the levels of Hsp70 are greatest at the peak of viral gene expression and that a large fraction of cellular Hsp70 is associated with vaccinia virus proteins suggest that Hsp70 is involved in vaccinia virus assembly. PMID- 1501280 TI - Cys residues of the hepatitis B virus capsid protein are not essential for the assembly of viral core particles but can influence their stability. AB - In the spherical capsid of hepatitis B virus (HBV), intermolecular disulfide bonds cross-link the approximately 180 p21.5 capsid protein subunits into a stable lattice. In this study, we used mutant capsid proteins to investigate the role that disulfide bonds and the four p21.5 Cys residues (positions 48, 61, 107, and 185) play in capsid assembly and/or stabilization. p21.5 Cys residues were either replaced by Ala or removed (Cys-185) by carboxyl-terminal truncation, creating Cys-minus mutants which were expressed in Xenopus oocytes via microinjected synthetic mRNAs. Fractionation of radiolabeled oocyte extracts on 10 to 60% sucrose gradients revealed that Cys-minus core proteins resolved into the nonparticulate and capsid forms seen for wild-type p21.5. On 5 to 30% sucrose gradients, nonparticulate Cys-minus core proteins sedimented as dimers of approximately 40 kDa. We conclude that Cys residues and disulfides are not required for the assembly of either HBV capsids or the dimers that provide the precursors for capsid assembly. Since assembly presumably demands an appropriate p21.5 tertiary structure, it is unlikely that Cys residues are required for proper p21.5 folding. However, Cys residues stabilize isolated p21.5 structures, as evidenced by the marked reduction in stability of Cys-minus dimers and capsids (i) in nonreducing sodium dodecyl sulfate-polyacrylamide gel electrophoresis and (ii) upon protease digestion. We discuss these results in the context of the HBV life cycle and the role of Cys residues in other proteins. PMID- 1501281 TI - Infectious Japanese encephalitis virus RNA can be synthesized from in vitro ligated cDNA templates. AB - Japanese encephalitis virus (JEV) is a positive-stranded enveloped RNA virus that belongs to the family Flaviviridae. Genomic JEV RNA is approximately 11 kb long and encodes 10 proteins, 3 structural and 7 nonstructural. A full-length cDNA copy of the JEV genome was constructed by in vitro ligation of two cDNA fragments which encode the 5' (nucleotide positions 1 to 5576) and 3' (nucleotide positions 5577 to 10976) halves of the genome. T7 RNA polymerase transcripts of the ligated full-length cDNA template were infectious when transfected into BHK-21 cells. To identify the recombinant virus, a silent mutation was introduced into the clone encoding the 3' half of the genome, which abolished an XbaI site at nucleotide position 9131. Virus recovered by transfection with the transcripts contained this silent mutation, confirming its identity. Recombinant and parent viruses were identical with respect to growth and plaque production in BHK-21 cells, envelope protein expression in C6/36 cells, and neurovirulence and immunogenicity in mice. Repeated attempts to obtain infectious RNA by transcription from full length JEV genome cDNA templates cloned into plasmid vectors were unsuccessful. Synthesis of infectious JEV RNA from in vitro-ligated JEV cDNA templates will be useful for molecular and genetic studies of flavivirus replication and virulence. PMID- 1501282 TI - The nef gene of simian immunodeficiency virus SIVmac1A11. AB - The role of the simian immunodeficiency virus (SIV) nef gene in viral replication was investigated in several tissue culture systems. SIVmac1A11 is a molecularly cloned virus which replicates in both peripheral blood mononuclear cells (PBMC) and macrophages, although no disease is observed in infected rhesus macaques. In this report, we demonstrate that SIVmac1A11 contains a full open reading frame for nef which specifies a 37-kDa protein. To investigate the effects of nef on viral replication, a 70-bp deletion was introduced into the nef gene of SIVmac1A11. Analysis of infected cell extracts by immunoblotting revealed that both SIVmac1A11 and nef deletion virus SIVmac1A11 delta nef produced the same viral proteins, except that Nef was absent in the mutant virus. The deletion mutation did not affect viral replication in PBMC, in monocyte-derived and alveolar macrophages obtained from rhesus macaques, and in human cell lines HUT 78 and CEMx-174. In addition, SIVmac1A11 and SIVmac1A11 delta nef exhibited similar patterns of cytopathologic changes and ultrastructural appearances in infected cells. SIVmac1A11 and SIVmac1A11 delta nef did not infect human tumor macrophage cell line U937, GCT, THP-1, or HL-60 cells, although virus was produced after these cells were transfected with either wild-type or nef mutant viral DNA. Similar levels of virus were recovered from U937 and THP-1 cells transfected with mutant and parental proviral DNAs. In transient expression assays in a T-cell line and a macrophage line, the nef protein of SIVmac1A11 did not significantly suppress or enhance expression of the chloramphenicol acetyltransferase reporter gene linked to the SIVmac long terminal repeat. Thus, abrogation of nef did not affect several in vitro properties of SIVmac1A11, including patterns of viral infection in rhesus PBMC, rhesus macrophages, or human T-cell lines. PMID- 1501283 TI - Identification and characterization of fusion and processing domains of the human immunodeficiency virus type 2 envelope glycoprotein. AB - The envelope glycoprotein of the human immunodeficiency virus type 2 (HIV-2) is synthesized as a polyprotein precursor which is proteolytically processed to produce the mature surface and transmembrane envelope glycoproteins. The processed envelope glycoprotein species are responsible for the fusion between the viral envelope and the host cell membrane during the infection process. The envelope glycoprotein also induces syncytium formation between envelope expressing cells and receptor-bearing cells. To characterize domains of the HIV-2 envelope glycoprotein involved in membrane fusion and in proteolytic processing, we introduced single amino acid mutations into the region of the HIV-2 surface glycoprotein corresponding to the principal neutralizing determinant (the V3 loop) of HIV-1, the putative HIV-2 envelope precursor-processing sequence, and the hydrophobic amino terminus of the HIV-2 transmembrane envelope glycoprotein. The effects of these mutations on syncytium formation, virus infectivity, envelope expression, envelope processing, and CD4 binding were analyzed. Our results suggest that the V3-like region of the HIV-2 surface glycoprotein and the hydrophobic amino terminus of the transmembrane glycoprotein are HIV-2 fusion domains and characterize the effects of mutations in the HIV-2 envelope glycoprotein precursor-processing sequence. PMID- 1501284 TI - Activation of the human immunodeficiency virus type 2 enhancer is dependent on purine box and kappa B regulatory elements. AB - Human immunodeficiency virus type 2 (HIV-2) displays several features which distinguish it from HIV-1. Among the differences in these two viruses are the responses of their enhancer regions to T-cell activation. For example, stimulation of HIV-1 transcription is largely dependent on two kappa B regulatory elements. In contrast, the HIV-2 enhancer has a single kappa B site and contains additional cis-acting sequences responsive to induction. One of these sites, previously termed CD3R, is a purine-rich site, also called PuB1, which is responsive to stimulation of the CD3 component of the T-cell receptor complex and binds Elf-1, a member of the ets proto-oncogene family. In this report, we examine the interaction of the PuB1 site with other sites in the HIV-2 enhancer. We demonstrate that the PuB1 site confers responsiveness to T-cell activators only in cooperation with additional enhancer elements. Induction of the HIV-2 enhancer is dependent on at least two other cis-acting regulatory elements in addition to PuB1 and kappa B. One of these elements is another purine-rich site (PuB2), which also binds recombinant Elf-1. An adjacent region, proximal to the PuB2 ets (pets) site, shows protection in DNase footprinting experiments with extracts from Jurkat T cells. Mutation of either the kappa B, PuB1, PuB2, or pets site significantly reduces the response of the HIV-2 enhancer to T-cell stimulation, an effect which is mediated at the RNA level. Therefore, activation of the HIV-2 enhancer is dependent on at least four cis-acting elements, only one of which is found in HIV-1, which act in synergy with one another. Despite their sequence similarity, the organization and function of the HIV-2 enhancer have diverged considerably from those of HIV-1. PMID- 1501285 TI - High level of surface CD4 prevents stable human immunodeficiency virus infection of T-cell transfectants. AB - CD4 is the principal receptor for the human immunodeficiency virus (HIV). We have isolated and studied CD4-expressing tumor cell clones made by expressing CD4 in the T-cell tumor line HSB. Two clones, one designated HSBCD4, a clone expressing low levels of CD4, and the other, HSB10xCD4, a high-expresser CD4+ clone, were studied for their ability to bind and replicate HIV. In contrast to many other CD4+ cells that down-modulate CD4 following HIV infection, the HSB10xCD4 clones continued to express high levels of surface CD4 following infection with HIV. Unlike infection of HSBCD4 or many other human CD4+ cells, HIV infection of HSB10xCD4 clone was short lived: p24 antigen, provirus, or coculturable virus was present for less than 14 days following infection with several strains of HIV-1 or with HIV-2. When infection was initiated by transfection of proviral DNA, high and low CD4 expressers initially produced p24 antigen at approximately the same level. However, high CD4 expressers produced coculturable virus only during the first few days following transfection, whereas low CD4 expressers transfected with HIV continued to produce virus beyond 6 weeks. Monoclonal antibody-mediated down-modulation of CD4 surface expression on HSB10xCD4 clones permitted these formerly HIV-resistant cells to become persistently infected with HIV. Thus, high concentrations of CD4 on the surface of an HIV-infected cell prevent persistent HIV infection of CD4+ cells. PMID- 1501287 TI - Site-specific mutagenesis of the 35-kilodalton protein gene encoded by Autographa californica nuclear polyhedrosis virus: cell line-specific effects on virus replication. AB - The gene encoding the 35-kDa protein (35k gene) located within the EcoRI-S genome fragment of Autographa californica nuclear polyhedrosis virus (AcMNPV) is transcribed early in infection. To examine its function(s) with respect to virus multiplication, we introduced specific mutations of this early gene into the AcMNPV genome. In Spodoptera frugiperda (SF21) culture, deletion of the 35K gene reduced yields of extracellular, budded virus from 200- to 15,000-fold, depending on input multiplicity. Mutant replication was characterized by dramatically diminished levels of late and very late (occlusion-specific) virus gene expression and premature cell lysis. In contrast, 35K gene inactivation had no effect on virus growth in cultured Trichoplusia ni (TN368) cells. Insertion of the 35K gene and its promoter at an alternate site (polyhedrin locus) restored virus replication to wild-type levels in SF21 culture. Subsequent insertion of 4 bp after codon 81 generated a frameshift mutant that exhibited a virus phenotype indistinguishable from that of 35K deletion mutants and demonstrated that the 35K gene product (p35) was required for wild-type replication in SF21 cells. Mutagenesis also indicated that the C terminus of p35, including the last 12 residues, was required for function. In complementation assays, wild-type virus bearing a functional 35K gene allele stimulated all aspects of 35K null mutant replication and suppressed early cell lysis. These findings indicated that p35 is a trans-dominant factor that facilitates AcMNPV growth in a cell line-specific manner. PMID- 1501286 TI - Lack of correlation between soluble CD4-induced shedding of the human immunodeficiency virus type 1 exterior envelope glycoprotein and subsequent membrane fusion events. AB - The noncovalent association of the gp120 and gp41 envelope glycoproteins of human immunodeficiency virus type 1 (HIV-1) is disrupted by soluble CD4 binding, resulting in shedding of the gp120 exterior envelope glycoprotein. This observation has led to the speculation that interaction of gp120 with the CD4 receptor triggers shedding of the exterior envelope glycoprotein, allowing exposure of gp41 domains necessary for membrane fusion steps involved in virus entry or syncytium formation. To test this hypothesis, a set of HIV-1 envelope glycoprotein mutants were used to examine the relationship of soluble CD4-induced shedding of the gp120 glycoprotein to envelope glycoprotein function in syncytium formation and virus entry. All mutants with a threefold or greater reduction in CD4-binding ability exhibited marked decreases in gp120 shedding in response to soluble CD4, even though several of these mutants exhibited significant levels of envelope glycoprotein function. Conversely, most fusion-defective mutants with wild-type gp120-CD4 binding affinity, including those with changes in the V3 loop, efficiently shed gp120 following soluble CD4 binding. Thus, soluble CD4 induced shedding of gp120 is not a generally useful marker for conformational changes in the HIV-1 envelope glycoproteins necessary for the virus entry or syncytium formation processes. Some gp120 mutants, despite being expressed on the cell surface and capable of efficiently binding soluble CD4, exhibited decreased gp120 shedding. These mutants were still sensitive to neutralization by soluble CD4, indicating that, for envelope glycoproteins exhibiting high affinity for soluble CD4, competitive inhibition may be more important than gp120 shedding for the antiviral effect. PMID- 1501288 TI - Antibody-dependent transcriptional regulation of measles virus in persistently infected neural cells. AB - Application of neutralizing anti-hemagglutinin antibodies to mouse neuroblastoma cells (NS20Y/MS) persistently infected with measles virus (MV) leads to a significant reduction of viral structural proteins within 6 days. While the transcriptional gradient for MV-specific mRNAs remained unaffected upon antibody treatment, the total amount of MV-specific transcripts dropped by 80% after 24 h. The expression of genomic RNA was affected similarly, with slightly slower time kinetics. Both transcription and expression of the viral structural proteins could be completely reactivated when viral antibodies were removed from the tissue culture. The same findings could be obtained in rat glioma cells persistently infected with subacute sclerosing panencephalitis virus (C6/SSPE) but not in cells of nonneural origin. The data indicate that antibody-induced antigenic modulation affects the early stages of viral transcription within a few hours after the addition of antibodies and leads to an almost complete repression of viral gene expression in cells of neural origin. PMID- 1501289 TI - Expression of the influenza A virus M2 protein is restricted to apical surfaces of polarized epithelial cells. AB - The M2 protein of influenza A virus is a small, nonglycosylated transmembrane protein that is expressed on surfaces of virus-infected cells. A monoclonal antibody specific for the M2 protein was used to investigate its expression in polarized epithelial cells infected with influenza virus or a recombinant vaccinia virus that expresses M2. The expression of M2 on the surfaces of influenza virus-infected cells was found to be restricted to the apical surface, closely paralleling that of the influenza virus hemagglutinin (HA). Membrane domain-specific immunoprecipitation indicated that the M2 protein was inserted directly into the apical membrane with transport kinetics similar to those of HA. In polarized cells infected with a recombinant vaccinia virus that expresses M2, we found that 86 to 93% of surface M2 was restricted to the apical domain compared with 88 to 90% of HA in a similar assay. These results indicate that the M2 protein undergoes directional transport in the absence of other influenza virus proteins and that M2 contains the structural features required for apical transport in polarized epithelial cells. The ultrastructural localization of the M2 protein in influenza virus-infected MDCK cells was investigated by immunoelectron microscopy using M2 antibody and a gold conjugate. In cells in which extensive virus budding was occurring, the apical cell membrane was labeled with gold particles evenly distributed between microvilli and the surrounding membrane. In addition, a significant fraction of the M2 label was apparently associated with virions. A monoclonal antibody specific for HA demonstrated a similar labeling pattern. These results indicate that M2 is localized in close proximity to budding and assembled virions. PMID- 1501290 TI - Effect of reciprocal complementation of two defective human immunodeficiency virus type 1 (HIV-1) molecular clones on HIV-1 cell tropism and virulence. AB - Human immunodeficiency virus type 1 (HIV-1) displays both interstrain and intrastrain genetic variability. Virus populations with extensive microheterogeneity have been defined as swarms or quasispecies. Many of the genomes within HIV-1 swarms appear to be defective in one or more genes required for viral replication. It is unclear to what extent defective viruses play a role in the process of HIV-1 infection or in the pathogenesis of AIDS. We have isolated two biologically active HIV-1 clones: LW 12.3, which contains defects in the vif and vpr genes, and MN ST.1, which has a defect in the vpu gene. LW 12.3 is unable to replicate in peripheral blood mononuclear cells (PBMC). The growth of MN-ST.1 in SupT1 cells is marked by a 3-week lag in extracellular virus production and by the presence of unusually abundant viral buds. We demonstrate here that coinfection of PBMC with these two partially defective HIV-1 clones extends the cellular host range of LW 12.3, significantly increases the replication rate of both viral genomes, and eliminates the delay in production observed with the vpu-defective MN ST.1. When the lesions in vpr and vif of LW 12.3 are repaired, the resultant virus grows normally in PBMC. This is also the case when only vif is repaired, indicating that complementation of LW 12.3 in PBMC by MN ST.1 is mediated by vif in trans. The reciprocal complementation results in a dramatic increase of HIV-1 virulence. This two-component model represents a simplified version of the in vivo situation and illustrates one way in which interaction of defective viruses could increase the spread of infection and progression of disease. PMID- 1501291 TI - In vivo binding of wild-type and mutant human immunodeficiency virus type 1 Rev proteins: implications for function. AB - The Rev transactivator protein of human immunodeficiency virus type 1 (HIV-1) is required for protein expression from the HIV-1 RNAs which contain a binding site for the Rev protein, termed the Rev-responsive element (RRE). This transactivator acts both at the level of splicing/transport of nuclear RNAs and at the level of translation of cytoplasmic RNAs. We used a monoclonal antibody specific for the HIV-1 Rev protein to immunoprecipitate cellular extracts from HIV-1-infected and transfected cells. High levels of specific binding of wild-type Rev to the RRE containing RNAs were found in cytoplasmic, but not nuclear, extracts from these cells. A Rev mutant which lacked both nuclear and cytoplasmic Rev function but retained RNA binding in vivo was generated. This binding was detectable with both nuclear and cytoplasmic extracts. These results verify the existence of direct binding of Rev to HIV-1 RNAs in vivo and conclusively prove that binding of Rev is not sufficient for nuclear or cytoplasmic Rev function. The results also support a direct role for Rev in the nuclear export and translation of HIV-1 RNAs. PMID- 1501292 TI - Tat- and Rev-directed antisense RNA expression inhibits and abolishes replication of human immunodeficiency virus type 1: a temporal analysis. AB - Replication of human immunodeficiency virus type 1 (HIV-1) was inhibited by stable intracellular expression of antisense RNA in the human T-lymphoid cell line Jurkat. When the viral subregion encoding the HIV-1 activator proteins was targeted, the extent of antisense RNA-mediated inhibition was greater than 97% during the first 2 weeks postinfection. Later in the time course, productive HIV 1 infection broke through at high initial infective doses. However, at initial multiplicities of infection equal to or smaller than 0.1, HIV-1 production was not detectable during the 5 weeks of observation. The results underline the effectiveness of stable intracellular antisense RNA expression in inhibiting HIV 1 replication. PMID- 1501293 TI - Contribution of the TATA motif to Tat-mediated transcriptional activation of human immunodeficiency virus gene expression. AB - Tat-mediated transcriptional activation of human immunodeficiency virus (HIV) gene expression requires the presence of the cis-acting Tat-responsive element, TAR, and a functional enhancer-promoter element. The ability of Tat to function with heterologous enhancer sequences led us to examine the role of the minimal basal promoter for trans activation. Substitution of HIV TATA sequences (nucleotides -20 to -35) with TATA elements derived from other promoters had little effect on the basal level of transcription or the ability to activate the HIV long terminal repeat upon stimulation through upstream activation sequences. In contrast, minimal alterations within the TATA motif had a profound effect on trans activation, as demonstrated by the 3- to 10-fold reduction in activation following expression of Tat. Our findings suggest that minor changes in the TATA motif affect the composition of the initiation-elongation complex and that the composition of this complex is critical for Tat-dependent activation of gene expression. PMID- 1501294 TI - Multimeric CD4 binding exhibited by human and simian immunodeficiency virus envelope protein dimers. AB - The envelope (Env) glycoproteins of human and simian immunodeficiency viruses (HIV and SIV) form noncovalently associated oligomers which mediate virus binding to the cell surface and fusion between the viral envelope and plasma membrane. A high-affinity interaction with CD4 is a critical step in this process. In this report, we show that Env protein dimers, but not monomers, can bind two CD4 molecules simultaneously. Multimeric CD4 binding may have important implications for Env protein-CD4 avidity, CD4-induced release of gp120, and subunit-subunit cooperativity during virus membrane fusion as well as for therapeutic strategies. PMID- 1501296 TI - Nonhomogeneous distribution of human immunodeficiency virus type 1 proviruses in the spleen. AB - A nonhomogeneous spatial distribution of human immunodeficiency virus type 1 proviruses in an infected spleen was observed. Antigenic stimulation of infected cells might explain this partition. PMID- 1501295 TI - Interactions of HTF4 with E-box motifs in the long terminal repeat of human immunodeficiency virus type 1. AB - We have identified three consensus E-box motifs in the long terminal repeat of human immunodeficiency virus type 1. One of these E boxes interacts selectively with representative members of the class A group of basic helix-loop-helix proteins, including HTF4, E47, and their heterodimers. Our analyses implicate the helix-loop-helix proteins in regulation of human immunodeficiency virus type 1 gene expression. PMID- 1501297 TI - Examination of potato virus X proteins synthesized in infected tobacco plants. AB - Nucleotide sequence analysis of potato virus X (PVX) genomic RNA predicts five open reading frames (ORFs). Previous analysis of total RNAs from PVX-infected leaf tissue suggested that six subgenomic RNAs are synthesized during infection. However, the proteins encoded by the genomic RNA, the subgenomic RNAs, or the predicted ORFs have not been identified in vivo. To characterize the coding properties of the viral RNA, particularly to determine whether the five predicted ORFs function in vivo, total protein extracts prepared from PVX-infected leaf tissue were analyzed by using antibodies raised against virus-specific synthetic peptides and against the virus capsid protein. Dot blot analyses showed that these antibodies reacted to PVX-infected extracts, indicating in vivo expression of the five predicted ORFs. In addition, Western blot (immunoblot) analysis of the extracts showed that ORF 1, 2, 3, and 4 peptide antisera and coat protein antiserum detect predominantly a single protein. PMID- 1501298 TI - Regulation of nuclear transport of a plant potyvirus protein by autoproteolysis. AB - The NIa proteinase encoded by tobacco etch potyvirus catalyzes six processing events, three of which occur by an autoproteolytic mechanism. Autoproteolysis is necessary to cleave the boundaries of both NIa and the 6-kDa protein, which is located adjacent to the N terminus of NIa in the viral polyprotein. As a consequence, NIa may exist in a free form or in a transient polyprotein form containing the 6-kDa protein. While the majority of NIa molecules localize to the nuclei of infected cells, a fraction of the NIa pool is attached covalently to the 5' terminus of genomic RNA in the cytoplasm. To determine whether the presence of the 6-kDa protein affects the nuclear transport properties of NIa, we have generated transgenic plants that express genes encoding a reporter enzyme, beta-glucuronidase (GUS), fused to NIa or NIa-containing polyproteins. The NIa/GUS fusion protein was detected by histochemical analysis in the nucleus. Similarly, an NIa/GUS fusion protein that arose by autoproteolysis of a 6 kDa/NIa/GUS polyprotein was found in the nucleus. In contrast, fusion protein consisting of 6-kDa/NIa/GUS, which failed to undergo proteolysis because of the presence of a Cys-to-Ala substitution in the proteolytic domain of NIa, was detected in the cytoplasm. The inhibition of NIa-mediated nuclear transport was not due to the Cys-to-Ala substitution, since this alteration had no effect on translocation in the absence of the 6-kDa protein. These results indicate that the 6-kDa protein impedes nuclear localization of NIa and suggest that subcellular transport of NIa may be regulated by autoproteolysis. PMID- 1501299 TI - The C terminus of human immunodeficiency virus type 1 matrix protein is involved in early steps of the virus life cycle. AB - Deletion mutations at the C terminus of the matrix (MA) protein of human immunodeficiency virus type 1 (HIV-1) were generated by site-directed mutagenesis. The resultant mutant viruses had a severe defect in virus infectivity. This defect did not involve late steps of the virus life cycle, as the synthesis and processing of the Gag polyprotein and the assembly and release of mutant virions were not greatly affected. The incorporation of viral proteins and the viral RNA genome was similar for mutant and wild-type virions. In contrast, the early steps of the virus life cycle were severely affected, as the synthesis of viral DNA postinfection was dramatically reduced in mutant-virus infected cells. One stretch of amino acids that was deleted in one of the mutants has significant homology with a region in VP1 of the picornavirus family. This region of VP1 is presumably involved in poliovirus penetration into cells. These results suggest that in addition to its functional role in virus assembly, the MA protein of HIV-1, and possibly of other retroviruses, plays an important role in virus entry. PMID- 1501300 TI - The precore gene of the woodchuck hepatitis virus genome is not essential for viral replication in the natural host. AB - A number of naturally occurring hepatitis B virus mutants that cannot synthesize the virus precore protein have been identified. Such mutants have been associated with more severe forms of hepatitis, including fulminant hepatitis. The most common mutation observed is a substitution of G to A in the distal precore gene that converts a codon specifying Trp (TGG) to a termination codon (TAG). Using oligonucleotide-directed mutagenesis, we have produced the same point mutation in the precore gene of an infectious clone of woodchuck hepatitis virus (WHV). Transfection of mutant WHV DNA into the livers of adult woodchucks resulted in replication of the mutant in three of three susceptible animals. Levels of virus replication and transient elevations in liver enzymes in serum were similar to those of adult animals infected with wild-type WHV. Virions, found to possess mutant precore genes by polymerase chain reaction amplification and DNA sequencing, were recovered from the serum of one of the animals and inoculated subcutaneously into neonatal woodchucks. They produced infection in all five animals studied. The level of virus replication in neonatal animals infected with this mutant virus was comparable to that found in neonatal woodchucks infected with wild-type WHV, but none of five woodchucks infected with the precore mutant virus as neonates became chronic virus carriers. It was concluded that the precore gene of the WHV genome is not essential for virus replication in the natural host but may be important for chronic infection. PMID- 1501301 TI - The downstream regulatory sequence of the adenovirus type 2 major late promoter is functionally redundant. AB - Mutagenesis of promoter sequences and oligonucleotide competition assays have been used to demonstrate the late-phase-specific stimulation of the adenovirus type 2 major late promoter is mediated by functionally redundant elements located between positions +75 and +125. These octamer motif-related sequences are recognized by multiple factors. PMID- 1501303 TI - Evolution of the V3 envelope domain in proviral sequences and isolates of human immunodeficiency virus type 1 during transition of the viral biological phenotype. PMID- 1501302 TI - Interference established in mice by infection with Friend murine leukemia virus. AB - Retroviral interference is manifested in chronically infected cells as a decrease in susceptibility to superinfection by virions using the same cellular receptor. The pattern of interference reflects the cellular receptor specificity of the chronically infecting retrovirus and is mediated by the viral envelope glycoprotein, which is postulated to bind competitively all cellular receptors available for viral attachment. We established retroviral interference in mice by infecting them with Friend murine leukemia virus and them measured susceptibility to superinfection by challenging the mice with the erythroproliferative spleen focus-forming virus. Infection of approximately 10% of nucleated splenocytes rendered mice 1% as susceptible to superinfection as untreated controls. The magnitude of this effect was the same in mice incapable of producing neutralizing antibodies or genetically deficient for T cells. The results indicated that retroviral interference in vivo was established rapidly with infection of a fraction of the host cell population and that the decrease in susceptibility to superinfection occurred without a detectable contribution by immunologic factors. PMID- 1501304 TI - Effect of a media blitz and a threatened lawsuit on stimulant treatment. AB - OBJECTIVE: To enumerate and evaluate changes in the rate of medication treatment for hyperactive/inattentive students subsequent to negative media publicity about methylphenidate (Ritalin) and related lawsuits threatened or initiated from late 1987 to early 1989. DESIGN: Biennial 1971 to 1991 school nurse surveys of medication treatment for hyperactive/inattentive students; a 1989 school nurse questionnaire on parent attitudes about medication; annual 1984 through 1991 hyperkinetic clinic treatment data; annual 1986 through 1990 Drug Enforcement Administration estimates of retail sales of methylphenidate, nationally and locally. PRIMARY SETTING: All public and private elementary and secondary schools in Baltimore County, Maryland. PATIENTS: Students receiving medication for hyperactivity/inattentiveness. RESULTS: Whereas the medication rate for the treatment of hyperactive/inattentive students in Baltimore County doubled every 4 to 7 years from 1971 through 1987, it declined 39% in the 1989 and 1991 surveys from its 1987 peak. This drop occurred after the 1987 through 1989 media blitz against methylphenidate and after a well-publicized threatened lawsuit locally. Parents became fearful of media-reported medication "side effects" and school staff hesitated to refer restless, impulsive, and inattentive students to physicians. Most inhibited from the prospect of medication treatment were less affluent parents and parents of hyperactive/inattentive elementary schoolchildren who had never received medication. Drug Enforcement Administration data revealed that the Baltimore metropolitan area had a far greater decline in methylphenidate use than that which occurred nationally. CONCLUSION: Strong circumstantial evidence suggests that the prominent 1989 and 1991 declines in the initiation of stimulant medication for hyperactive/inattentive students were related to the apprehension of parents and involved professionals generated by the methylphenidate media blitz and the threatened lawsuit. PMID- 1501305 TI - Survey of advertising for nutritional supplements in health and bodybuilding magazines. AB - The use of food supplements by the general public is poorly quantified, and little information on this subject is available in the medical literature. We surveyed 12 recent issues of popular health and bodybuilding magazines (1) to quantify the number of advertisements for food supplements, the number of products advertised, and the number and type of ingredients in these products; (2) to identify the purported health benefits of these products; and (3) as a preliminary effort to identify areas for future research. We counted 89 brands, 311 products, and 235 unique ingredients, the most frequent of which were unspecified amino acids; the most frequently promoted health benefit was muscle growth. We also found many unusual or unidentifiable ingredients, and 22.2% of the products had no ingredients listed in their advertisements. Health professionals may not be aware of how popular food supplements are or of a particular supplement's potential effects or side effects. In addition, patients may be reluctant to discuss their use of these products with traditional medical practitioners. We recommend that routine history taking include specific questions about patients' use of food supplements and that any possible adverse effects or side effects be reported to public health authorities. PMID- 1501306 TI - The definition of alcoholism. The Joint Committee of the National Council on Alcoholism and Drug Dependence and the American Society of Addiction Medicine to Study the Definition and Criteria for the Diagnosis of Alcoholism. AB - To establish a more precise use of the term alcoholism, a 23-member multidisciplinary committee of the National Council on Alcoholism and Drug Dependence and the American Society of Addiction Medicine conducted a 2-year study of the definition of alcoholism in the light of current concepts. The goals of the committee were to create by consensus a revised definition that is (1) scientifically valid, (2) clinically useful, and (3) understandable by the general public. Therefore, the committee agreed to define alcoholism as a primary, chronic disease with genetic, psychosocial, and environmental factors influencing its development and manifestations. The disease is often progressive and fatal. It is characterized by impaired control over drinking, preoccupation with the drug alcohol, use of alcohol despite adverse consequences, and distortions in thinking, most notably denial. Each of these symptoms may be continuous or periodic. PMID- 1501307 TI - Multiple false-positive serologic tests for HIV, HTLV-1, and hepatitis C following influenza vaccination, 1991. AB - OBJECTIVE: (1) To assess factors associated with the occurrence of multiple false positive viral enzyme-linked immunosorbent assays (ELISAs) for human immunodeficiency virus (HIV), human T-cell lymphotrophic virus type 1 (HTLV-1), and hepatitis C virus (HCV) among individual blood donors and (2) to determine the frequency and time course of this phenomenon. DESIGN: Case-control study. SETTING: A regional blood center. PARTICIPANTS: Blood donors found to have multiple false-positive viral ELISAs (case donors) and randomly selected seronegative controls (control donors) who donated between October 31, 1991, and December 15, 1991. An additional random sample of 262 donation records was reviewed to calculate the proportion of donors who received influenza vaccine. MAIN OUTCOME MEASURES: Multiple false-positive viral ELISAs, receipt of influenza vaccination formulated for the 1991-1992 influenza season, and follow-up ELISA results on serum samples obtained from case donors. RESULTS: Among 17,941 donors, 10 case donors were identified. Nine of the 10 case donors received influenza vaccine, compared with three of 30 control donors (odds ratio [OR] = 81; 95% confidence interval [CI], 6 to 3670; P less than .001). Among nine case donors, the mean time between vaccination and blood donation was 26 days (range, 9 to 68 days). Follow-up ELISAs of serum samples from seven case donors obtained 52 to 130 days (mean, 75 days) after vaccination demonstrated reversion to HIV and HTLV 1 seronegativity in all but one specimen, with persistence of positive HCV ELISAs in four specimens. We estimate between 0.6% and 1.7% of blood donors who received influenza vaccine this season had multiple false-positive viral ELISAs. CONCLUSIONS: The occurrence of multiple false-positive viral ELISAs among blood donors was associated with influenza vaccination, but was infrequent among vaccinees. This phenomenon is of short duration for HIV and HTLV-1, but may persist longer for HCV. We recommend influenza vaccinees not be deferred from blood donation. Blood donors with multiple false-positive viral ELISAs should be considered for future reentry as blood donors. PMID- 1501308 TI - NIH consensus conference. Diagnosis and treatment of depression in late life. PMID- 1501309 TI - Does smoke get in your eyes? PMID- 1501310 TI - TV or not TV. Communicating health information to the public. PMID- 1501311 TI - A Piece of my mind. Sunday rounds. PMID- 1501312 TI - Congress wants alternative therapies studied; NIH responds with programs. PMID- 1501313 TI - Next step, if any, lies with NIH in alleged scientific fraud; nobelist claims vindication. PMID- 1501314 TI - Latest from pertussis front: Swedish vaccine. PMID- 1501315 TI - From the Surgeon General, US Public Health Service. PMID- 1501316 TI - From the Centers for Disease Control. Outbreak of type E botulism associated with an uneviscerated, salt-cured fish product--New Jersey, 1992. PMID- 1501317 TI - From the Centers for Disease Control. Public-sector vaccination in response to measles. PMID- 1501318 TI - From the Centers for Disease Control. Coronary heart disease incidence, by sex. PMID- 1501319 TI - From the Centers for Disease Control. Estimated national spending on disease and injury prevention--United States, 1988. PMID- 1501320 TI - Predictors of achievement in academic medicine. PMID- 1501321 TI - Predictors of achievement in academic medicine. PMID- 1501322 TI - The sans of time. PMID- 1501323 TI - Violence in the hospital. PMID- 1501324 TI - A prospective study of cigarette smoking and risk of cataract in men. AB - OBJECTIVE: To examine the association between cigarette smoking and the incidence of cataract. DESIGN, SETTING, AND PARTICIPANTS: The design was a prospective cohort study using data from the Physicians' Health Study, a randomized trial of aspirin and beta carotene among 22,071 US male physicians aged 40 to 84 years that began in 1982. This analysis includes the 17,824 physicians who did not report cataract at baseline and did provide complete risk factor information. Based on information reported at baseline, 10% were current smokers, 39% were past smokers, and 51% were never smokers. MAIN OUTCOME MEASURE: An incident cataract was defined as a self-report confirmed by medical record review to have been first diagnosed after randomization, age-related in origin, and responsible for a decrease in best corrected visual acuity to 20/30 or worse. MAIN RESULTS: During 60 months of follow-up, 557 incident cataracts among 371 participants were confirmed. Compared with never smokers, current smokers of 20 or more cigarettes per day had a statistically significant increase in the risk of cataract (relative risk [RR], 2.16; 95% confidence interval [Cl], 1.46 to 3.20; P less than .001). Similar results were obtained after simultaneously controlling for other potential cataract risk factors in a logistic regression model (RR, 2.05; 95% Cl, 1.38 to 3.05; P less than .001). Among the 557 eyes with cataract, nuclear sclerotic changes were present in 442 while posterior subcapsular changes were present in 204. After controlling for other potential cataract risk factors, current smokers of 20 or more cigarettes per day had statistically significant increases in nuclear sclerosis (RR, 2.24; 95% Cl, 1.47 to 3.41; P less than .001) and posterior subcapsular (RR, 3.17; 95% Cl, 1.81 to 5.53; P less than .001) cataract. Past smokers had an elevated risk of posterior subcapsular (RR, 1.44; 95% Cl, 0.97 to 2.13; P = .07) but not nuclear sclerosis cataract. For current smokers of fewer than 20 cigarettes per day, no increased risks were observed of total, nuclear sclerosis, or posterior subcapsular cataract. CONCLUSIONS: These data provide support for the hypothesis that cigarette smoking increases the risk of developing both nuclear sclerosis and posterior subcapsular cataract. PMID- 1501325 TI - A prospective study of cigarette smoking and risk of cataract surgery in women. AB - OBJECTIVE: To examine prospectively the association between cigarette smoking and the risk of cataract extraction in women. DESIGN: Prospective cohort study beginning in 1980 with 8 years of follow-up. SETTING: United States, multistate. PARTICIPANTS: Registered nurses 45 to 67 years of age and free of diagnosed cancer. There were 50,828 women included in 1980 and others were added as they became 45 years of age. MAIN OUTCOME MEASURE: Incidence of senile cataract extraction. RESULTS: We documented 493 incident senile cataracts diagnosed and extracted during 470,302 person-years of follow-up. The age-adjusted relative risk (RR) among women who smoked at least 65 pack-years was 1.63 (95% confidence interval [Cl], 1.18 to 2.26; P for trend, .02). A similar increase in RR was noted when smoking was assessed in terms of number of cigarettes currently smoked or number of cigarettes smoked by past smokers. Results were also similar after adjusting for other potential risk factors for cataract. Smoking was also strongly associated with posterior subcapsular cataract specifically (RR, 2.59; 95% Cl, 1.49 to 4.50 for greater than or equal to 65-pack-year smokers relative to nonsmokers. CONCLUSION: Smoking appears to increase the risk of cataract extraction. PMID- 1501326 TI - Medical researchers and the media. Attitudes toward public dissemination of research. AB - OBJECTIVE: To study the experience of recently published authors with the news media. DESIGN: A self-administered questionnaire. PARTICIPANTS: All first authors of scientific articles published in JAMA and The New England Journal of Medicine during a 6-month period. Of 397 surveyed, 92% responded. MAIN OUTCOME MEASURES: Researchers were asked about (1) their experience with the news media, (2) their attitudes toward the dissemination of health-related research to the general public, and (3) their attitudes toward the lay press. RESULTS: Of respondents, 65% stated that their research was discussed in the lay press, and 60% reported that they were directly contacted by the press. Researchers had positive attitudes toward the press; 86% reported that news reports based on their research were accurate and 44% felt that media coverage would help them achieve their overall professional goals. Positive aspects of media coverage most frequently endorsed were that (1) it improves the image of the profession, (2) it informs the professional community of their research, and (3) it allows the public to understand the topic better. Negative aspects of media coverage were (1) it gives the impression that the researcher is seeking publicity, (2) it creates jealousy among colleagues, and (3) it takes too much time. Researchers were not eager to change the existing dissemination process, yet they endorsed the need for uniform standards concerning relations with the press. CONCLUSIONS: The majority of first authors in two leading medical journals reported substantial media coverage of their research, expressed generally positive sentiments about the press coverage of their work, and expressed a need for consensus on interactions involving the press. PMID- 1501327 TI - A piece of my mind. The intubation. PMID- 1501328 TI - Educational programs in US medical schools. AB - Trends of the past few years indicate that the 1990s will be a time of intense activity in medical education reform. A number of areas described in this annual review of medical education are grounds for optimism, tempered, however, by caution. The applicant pool has been increasing rapidly over the past 2 years and has reached the levels of the early 1980s. The average proportion of women and some minorities also has been rising. While these are positive signs, efforts to ensure diversity in the student population should not be abandoned. The number of faculty members continues to rise, especially in the clinical disciplines. The increases, occurring in the context of stable medical student enrollments, raise questions about the various roles and responsibilities of medical school faculty. Many medical schools are in the process of curriculum review and revision; while these changes respond to identified problems, they may have implications for faculty and other resources. External financial support fueled previous waves of curriculum innovation, and some of these gains could not be maintained when that support was withdrawn. The revisions in the examinations of the NBME are being well received, and the single pathway to licensure through USMLE has been initiated. This system does, however, affect graduates' options for licensure. Finally, the increased interest in program evaluation, especially the definition of goals and the measurement of educational outcomes to assess their attainment, demonstrates that medical schools are serious about educational accountability. Some schools also are being asked to address externally imposed objectives, related specifically to specialty choice, creating a potential for conflict between the objectives that the medical school sets for itself and those mandated by its external constituencies. While this analysis may imply that medical education is now in a "good news/bad news" situation, the message is that planning and careful assessment of options are perhaps even more important today than they were in the past. Change has its costs and its implications, but it must nonetheless be undertaken. PMID- 1501329 TI - Financial assistance and education programs to encourage care to the underserved. PMID- 1501330 TI - Liaison Committee on Medical Education. Past successes, future challenges. PMID- 1501331 TI - Report of the Medical Schools Section Primary Care Task Force. PMID- 1501332 TI - The organization and financing of graduate medical education in Canada. PMID- 1501334 TI - Continuing medical education. Unabated debate. PMID- 1501333 TI - Evidence for the effectiveness of CME. A review of 50 randomized controlled trials. AB - OBJECTIVE: To assess the impact of diverse continuing medical education (CME) interventions on physician performance and health care outcomes. DATA SOURCES: Using continuing medical education and related phrases, we performed regular searches of the indexed literature (MEDLINE, Social Science Index, the National Technical Information Service, and Educational Research Information Clearinghouse) from 1975 through 1991. In addition, for these years, we used manual searches, key informants, and requests to authors to locate other indexed articles and the nonindexed literature of adult and continuing professional education. STUDY SELECTION: From the resulting database we selected studies that met the following criteria: randomized controlled trials; educational programs, activities, or other interventions; studies that included 50% or more physicians; follow-up assessments of at least 75% of study subjects; and objective assessments of either physician performance or health care outcomes. DATA EXTRACTION: Studies were reviewed for data related to physician specialty and setting. Continuing medical education interventions were classified by their mode(s) of activity as being predisposing, enabling, or facilitating. Using the statistical tests supplied by the original investigators, physician performance outcomes and patient outcomes were classified as positive, negative, or inconclusive. DATA SYNTHESIS: We located 777 CME studies, of which 50 met all criteria. Thirty-two of these analyzed physician performance; seven evaluated patient outcomes; 11 examined both measures. The majority of the 43 studies of physician performance showed positive results in some important measures of resource utilization, counseling strategies, and preventive medicine. Of the 18 studies of health care outcomes, eight demonstrated positive changes in patients' health care outcomes. CONCLUSION: Broadly defined CME interventions using practice-enabling or reinforcing strategies consistently improve physician performance and, in some instances, health care outcomes. PMID- 1501335 TI - Accreditation of allied health education. Assessing for educational effectiveness. PMID- 1501336 TI - Allied health education in rural health professional shortage areas of the United States. PMID- 1501337 TI - Health care reform and the medical education imperative. PMID- 1501338 TI - Lifelong learning tailored to individual clinical practice. PMID- 1501339 TI - Challenge to osteopathic education. Returning to its primary care roots. PMID- 1501340 TI - An overview of reform initiatives in medical education. 1906 through 1992. PMID- 1501341 TI - The Robert Wood Johnson Foundation Commission on Medical Education. The sciences of medical practice, summary report. PMID- 1501342 TI - Education as part of the health care solution. Strategies from the Pew Health Professions Commission. PMID- 1501343 TI - US medical school finances. PMID- 1501344 TI - Medical schools in the United States and Canada. PMID- 1501345 TI - Graduate medical education. PMID- 1501346 TI - Medical education and financial assistance programs sponsored by US government agencies. PMID- 1501347 TI - AIDS and the medical student: the risk of contagion and the duty to treat. PMID- 1501348 TI - Do not substitute: physicians should teach medical students. PMID- 1501349 TI - Writing is my best defense. PMID- 1501350 TI - Jonathan E. Rhoads Lecture. Body composition research: implications for the practice of clinical nutrition. PMID- 1501351 TI - Polyamine excretion in depleted patients with gastrointestinal malignancy: effect of perioperative nutrition and tumor removal. AB - Polyamines, synthesized by all mammalian cells, are involved in protein and energy metabolism. We measured urinary excretion of polyamines, putrescine, spermidine, spermine, and their metabolites N1-acetylspermidine and N8 acetylspermidine, resting energy expenditure, and nitrogen excretion in 12 depleted patients with gastrointestinal malignancy during preoperative and postoperative parenteral nutrition and in 7 patients with multiple trauma receiving similar parenteral nutrition. During preoperative nutrition support, the excretion of putrescine (p less than .05) and total polyamines (p less than .01) increased by 420% and 60%, respectively. Increases in energy balance and resting energy expenditure during nutrition could entirely explain the observed changes in polyamine excretion. Preoperatively, the excretion of N1 acetylspermidine (p less than .05), N8-acetylspermidine (p less than .001) and total polyamines (p less than .05) was higher in patients with a surgically noncurable tumor than in those with a surgically curable tumor. The energy balance and resting energy expenditure could also explain the differences in polyamine excretion between patients with surgically curable and noncurable disease, excluding the increased N8-acetylspermidine. Postoperatively, the excretion of N8-acetylspermidine in patients with multiple trauma without malignancy and in patients with palliative operation was similar, and was higher than in patients with a totally resected malignancy (p less than .01). Our results suggest that the excretion of polyamines reflects the activity of energy metabolism in general and that polyamine excretion is not specific for any particular disease. PMID- 1501352 TI - Interaction of protein and zinc malnutrition with the murine response to infection. AB - Malnutrition increases the host's susceptibility to infection. However, the mechanisms are not well understood. This study examined the interaction of protein and zinc underfeeding in mice before challenge with an intracellular pathogen, Salmonella typhimurium. C3H/HeN mice (n = 68) were weighted and placed on one of four diets: 20% ovalbumin with adequate zinc (20% NL), 20% ovalbumin without zinc (20% LO), 1% ovalbumin with zinc (1% NL), and 1% ovalbumin without zinc (1% LO). At the end of 6 weeks they were again weighed and then challenged with 10(4) S. typhimurium intraperitoneally. Mortality was recorded over the next 2 weeks. Although weight loss was markedly affected by protein malnutrition (two way analysis of variance: p = .0001), there was no independent effect by zinc (p = .3459). Similarly, protein malnutrition alone affected mortality rates (chi 2: p = .0001), whereas zinc had no independent effect (p = .7166). However, both protein and zinc underfeeding shortened the length of survival (Mann-Whitney U test: p less than .001). We conclude that protein malnutrition is the dominant factor influencing weight loss and mortality in this model. However, zinc malnutrition does shorten the length of survival and may contribute to the global immunosuppression noted in malnourished subjects. PMID- 1501353 TI - Metabolic effect of short-term total parenteral nutrition highly enriched with leucine or valine in rats recovering from severe trauma. AB - The metabolic impact of infusing a large amount of leucine (Leu) or valine (Val) was examined with regard to the corrective effect of total parenteral nutrition (TPN). Rats recovering from severe sepsis received either Leu- or Val-enriched TPN solution for 30 hours. The in vivo behavior of the amino acids administered was explored by a pulse injection of 14C-labeled Leu or Val. The recovery of 14CO2 from Leu increased by 64% in the septic rats of Leu-TPN group (41% of dose; p less than .01), as compared with control rats receiving the same TPN solution, whereas no significant rise in the 14CO2 recovery from Val occurred in the septic rats given Val-TPN (45% of dose) in comparison with the corresponding controls. The enhancement of Leu catabolism to CO2 in the Leu-TPN group was compatible with the alterations of urinary nitrogen excretion, plasma Leu level, and metabolite contents of liver and muscle. The only difference in metabolite levels observed between the two TPN groups was in hepatic total adenine nucleotides. Plasma amino acid levels were largely unaffected by infusion of these TPN solutions highly enriched with branched-chain amino acids (45%), except for an approximately threefold elevation of the Val level in Val-TPN rats. Thus, when administered in a large quantity during such short-term TPN, Leu can exert its metabolic effect without causing an imbalance in plasma amino acids under severe catabolic conditions. PMID- 1501354 TI - Thiamine, riboflavin, folate, and vitamin B12 status of low birth weight infants receiving parenteral and enteral nutrition. AB - Thirty infants were randomly assigned to receive either 3 mL of MVI-Pediatric supplement (PAR3 group, parenterally fed) or 2 mL (PAR2 group, parenterally fed). For the first week, 100% received total parenteral nutrition (TPN), 50% by the second, and less than 33% by the third. Eighteen control infants received enteral feeds of infant formula. Baseline (before TPN) and subsequent weekly blood samples, dietary data, and 24-hour urine collections were obtained. The adequacies of thiamine and riboflavin were assessed by the thiamine pyrophosphate effect and erythrocyte glutathione reductase activity, respectively. Urinary thiamine and riboflavin levels were measured by fluorometry. Plasma folate, red blood cell folate, urinary folate, and plasma vitamin B12 concentrations were determined by radioassay. No differences between groups were observed in thiamine pyrophosphate effect, erythrocyte glutathione reductase activity, urinary B1 or B2, or red blood cell folate levels at any time. Plasma folate differed (p less than .05) among the PAR3 group (24 +/- 7 ng/mL), and both the PAR2 (13 +/- 5 ng/mL) and enterally fed (ENT) groups (16 +/- 3 ng/mL) before the initiation of feeds, at week 1 (PAR3 = 32 +/- 15 ng/mL; PAR2 = 18 +/- 4 ng/mL; ENT = 19 +/- 9, ng/mL) and between the PAR3 (30 +/- 16 ng/mL) and PAR2 (16 +/- 4 ng/mL) infants at week 2. Plasma vitamin B12 levels differed among the ENT groups (551 +/- 287 pg/mL) and both the parenteral groups (PAR2 = 841 +/- 405 pg/mL; PAR3 = 924 +/- 424 pg/mL) at week 1 and between the ENT (530 +/- 238 pg/mL) and PAR3 (999 +/- 425 pg/mL) groups at week 2.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1501356 TI - Effects of pectin and cellulose on fat absorption after massive small-bowel resection in weanling rats. AB - The effects of pectin and cellulose on fat absorption after massive small-bowel resection were studied in rats. Weanling Wistar rats underwent 80% resection of the small intestine with gastrostomy, and fat emulsion labeled with 14C-linoleate was given via a gastrostomy tube for the fat absorption test on the 10th postoperative day. They were classified into three groups by diet as follows: E group, a fiber-free, chemically defined diet (CDD); EP group, CDD with 2% pectin; and EC group, CDD with 2% cellulose. The cumulative and hourly output of 14C in the expired air, the absorption rate of 14C in the intestine, and the metabolic utilization rate of 14C were calculated. The cumulative 14CO2 output was significantly lower in the EC group than in the E and EP groups. However, there was no significant difference in the 14CO2 output between the E and EP groups. The highest hourly 14CO2 output in the E and EP groups was observed during the first 2 hours. However, in the EC group, this fluctuated at low levels. No significant difference in the 1-14C-linoleate absorption rate was observed between the E and EP groups, whereas it was significantly lower in the EC group than in the E and EP groups. The metabolic utilization rate of 1-14C-linoleate showed no significant difference among the three groups. These data suggest that an addition of pectin to CDD does not impair small intestinal absorption of 1-14C linoleate after massive small-bowel resection, and an addition of cellulose decreases absorption of 1-14C-linoleate. PMID- 1501355 TI - Muscle protein degradation in severely malnourished patients with chronic obstructive pulmonary disease subject to short-term total parenteral nutrition. AB - Patients with chronic obstructive pulmonary disease (COPD) often lose weight and muscle mass with progression of the disease. Muscle protein degradation in patients with COPD has never been examined before and during hypercaloric feeding. Eight severely malnourished patients with COPD were examined at home consuming their usual intake, in the hospital after 3 days of a meat-free regular oral diet (period B), and during a hypercaloric (55 kcal/kg) high-lipid (55%) parenteral formula (total parenteral nutrition [TPN]). During period B, 8 well nourished patients and 10 malnourished cancer patients were used as control groups. Measurements included plasma assays, leg blood flow, leg exchange (of 3 methylhistidine [3MeH], glucose, lactate, and oxygen) and urinary measures of 3MeH, creatinine, and nitrogen. During period B, net release of 3MeH across the leg in patients with COPD was similar to that in well-nourished control subjects and cachectic cancer patients. In COPD patients, there was only a transient decrease in leg exchange values of 3MeH with administration of TPN. COPD patients demonstrated a reduction (p less than .01) in urinary 3MeH excretion and an increase in nitrogen balance (p less than .01) with TPN compared with period B. The decrease in muscle protein degradation with administration of TPN accounts for about 50% of the increase in nitrogen retention in patients with COPD. These data suggest that in severely malnourished patients with COPD the weight loss is not dependent on increased rates of skeletal muscle protein degradation; nevertheless, degradation rates attenuate with a positive nitrogen balance during nutrition repletion. PMID- 1501357 TI - Effects of amino acids in mixtures given by enteral or parenteral route on intestinal morphology and hydrolases in rats. AB - This study compares the effects of amino acid addition to an elemental liquid diet containing carbohydrates and triglycerides given either intragastrically or intravenously on the morphology and on hydrolase activities in the jejunum and ileum of adult rats. The isocaloric mixtures were administered for 4 days and control rats received an isocaloric laboratory diet orally. Independent of their content in amino acid, all mixtures given intravenously caused a drop in mucosal weight and a shortening of the height of the villi in both the jejunum and ileum. By enteral route, the addition of amino acids to a carbohydrate-triglyceride liquid diet led to the maintenance of normal villus height (this effect being prominent in the ileum) and to a significant increase of jejunal sucrase and aminopeptidase activities when compared with the carbohydrate-triglyceride mixture. Feeding the mixtures by parenteral route caused a significant drop of both enzyme activities. In contrast, lactase activity was generally not modified by the route of nutrient administration or by the composition of the diets. However, the absence of amino acid in the mixture given intravenously caused a specific drop of lactase activity in the ileum. Ileal sucrase activity was lowered dramatically by intragastric or intravenous feeding of the elemental diets. This effect was not modulated by the presence of amino acids. The presence of amino acids caused a significant drop of aminopeptidase activity in the ileum independently of the route of administration when compared with animals receiving the carbohydrate-triglyceride liquid diet.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1501358 TI - Duplex Doppler ultrasound identifies veins suitable for insertion of central feeding catheters. AB - Central venous access for feeding catheters may prove difficult in patients who have had numerous previous central line insertions or complications. Duplex Doppler ultrasound was used to identify the anatomy and patency of major central veins in 11 patients in whom attempts at obtaining central venous access by an experienced operator had failed at least once and in 40 control subjects. Doppler ultrasound demonstrated the subclavian veins (diameter 12.5 +/- 3.5 mm, mean +/- SE) and internal jugular veins (11 +/- 3.5 mm) in all the control subjects. In the patients, 18 of 44 veins were patent, 11 were small or had low blood flow, and 15 were thrombosed. In 7 patients who required central feeding catheter insertion, a suitable vein was identified and the catheter suitably placed, even in 3 subjects where no central vein was considered normal. Duplex Doppler ultrasonography is a useful technique for identifying veins suitable for the insertion of central venous lines when access has previously proved difficult. PMID- 1501359 TI - Vancomycin stability in heparin and total parenteral nutrition solutions: novel approach to therapy of central venous catheter-related infections. AB - To facilitate therapy of central venous catheter-related Gram-positive bacterial infection in patients who require total parenteral nutrition (TPN) therapy, we studied the stability of vancomycin in a commonly used TPN solution (V-TPN) at final concentrations of 0.5 mg/mL and 1.0 mg/mL and in heparin (100 U/mL in 0.9% NaCl) at 25 micrograms/mL (V-H). Vancomycin concentrations in V-TPN and V-H after storage at 4 degrees C over 35 and 14 days, respectively, were stable (within 10% of the prestorage vancomycin concentration). After 14 days at 4 degrees C heparin activity in V-H solution was 100 +/- 4% of that noted initially. Vancomycin remained stable (100 +/- 6% of the original vancomycin concentration) when the previously refrigerated V-TPN was held for an additional 24 hours at 22 degrees C. When the previously refrigerated V-H was held for an additional 24 hours at 37 degrees C, vancomycin concentrations decreased to 78 +/- 9% of the baseline concentrations (p less than .001). The stability of vancomycin in this TPN solution allows the daily dose of vancomycin to be mixed with the solution and then infused over 10 hours. As shown with pharmacokinetic modeling, this form of therapy will achieve serum vancomycin concentrations within the therapeutic range throughout a 24-hour period. The relative stability of vancomycin in a heparin line-flush solution allows vancomycin concentration in the lumen of the catheter to be maintained at greater than or equal to 15 micrograms/mL during the interval between catheter flushing and the subsequent TPN infusion. A simplified method of administering vancomycin to patients receiving concurrent TPN is possible. PMID- 1501360 TI - Different quantities of two commercial liquid diets consumed by weight-losing cancer patients. AB - Twenty ambulatory, weight-losing patients with advanced cancer of the lung, breast, or ovary were randomized to supplement their diet for 2 months with either of two commercial complete liquid diets, one containing intact milk proteins and the other partially hydrolyzed soy proteins. Both products were prescribed as sip feeds in addition to normal food. The patients consumed more of the hydrolysate-containing product than of that with intact (milk) protein. The difference was significant and was maintained during both months of the study. An increase in total energy and protein was obtained in both groups, but was significant only with the hydrolysate product. At the end of the study there was no group difference in measures of nutritional status, but weight loss was halted in both groups. PMID- 1501361 TI - Metabolic clearance of a fat emulsion containing medium-chain triglycerides in cirrhotic patients. AB - Medium-chain triglycerides (MCTs) may be advantageous in cirrhotic patients, but data on the clearing capacity are lacking. Intravenous fat tolerance test (IVFTT) was performed on 28 cirrhotic patients (Child's A, n = 9; Child's B, n = 13; Child's C, n = 6) to determine the clearance rate of Lipofundin MCT 20%, which contains a physical mixture of MCT and long-chain triglycerides (LCT). The mean fractional elimination rate (k2) of MCT/LCT physical blend in the cirrhotic patients (7.72%/min) was comparable with that of the healthy control subjects (n = 9, k2 = 5.43%/min). Significantly higher serum free fatty acid (FFA) levels were found in the cirrhotic patients during IVFTT. The difference could be accounted for by their higher basal levels. In all patients, serum FFA concentrations returned to basal value at the end of 1 hour. Prompt appearance of glycerol and beta-hydroxybutyrate was seen during IVFTT, indicating that hydrolysis of triglycerides and release of ketone bodies from the liver were rapid. It was concluded that the ability to eliminate MCT/LCT physical blend was not impaired in the cirrhotic patients. PMID- 1501362 TI - Inadvertent arterial administration of parenteral hyperalimentation solution resulting in generalized seizure activity. AB - Serious complications may arise from improper central venous catheter placement. In this case report, seizures occurred as a result of inadvertent arterial administration of parenteral hyperalimentation. There is a need for radiographic confirmation of central venous catheter position by qualified personnel before catheter use. PMID- 1501363 TI - Subcutaneous jejunostomy. AB - When the surgeon must obviate to an impending obstruction because of an unresectable tumor of the supramesocolic space and an intestinal bypass is not feasible, a jejunostomy is usually indicated. We describe a new method to provide enteral nutrition via a subcutaneous jejunostomy without any external device, which can be used only when the patient is at risk for developing an obstruction or dysphagia. The feeding tube is inserted into the jejunum and then connected to a Port-a-Cath lodged in a subcutaneous pocket. Subsequently, the nutrition can be delivered via a Huber needle inserted in the port, or, to minimize the need for strict aseptic surveillance, the tube can be exteriorized from the pocket and used as the usual tube jejunostomy. This procedure allows placing a precautionary jejunostomy without distortion of the body-image. PMID- 1501364 TI - Accelerated improvement of alcoholic liver disease with enteral nutrition. PMID- 1501365 TI - Stimulation of protein synthesis in human tumors by parenteral nutrition: evidence for modulation of tumor growth. PMID- 1501366 TI - Effect of a short-term infusion of intravenous fat on serum lipids. PMID- 1501367 TI - Stability of three-in-one TPN solutions. PMID- 1501368 TI - Muscle glutamine concentration and protein synthetic rate. PMID- 1501369 TI - [Hemodynamics of intrahepatic portal vein studied in healthy subjects and liver cirrhosis by pulsed Doppler method]. AB - The hemodynamics of the intrahepatic portal vein in 35 healthy subjects and 74 patients with liver cirrhosis was studied by measuring blood flow velocity with pulsed Doppler ultrasound technique. The flow velocity of portal vein decreased from the portal trunk to the first branches and to the second branches in the right and left lobes. Especially, an abrupt decrease of the flow velocity in the umbilical part of the left portal vein was characteristic of hemodynamics in the intrahepatic portal vein. The flow velocity in the third branches decreased more than that of the second branch in the right portal vein, but did not exist in the left. And the velocity was almost equal in all the subsegments. Blood clots of the left portal vein in 25 of 36 lesions were found in 31 patients with intrahepatic portal vein thrombus. This characteristic hemodynamics of the left portal vein was thought to be the main cause for the formation of blood clots. In the group with liver cirrhosis, the flow velocity was lower than in healthy subjects in the portal trunk, bilateral first branches and right second branches, but did not exist in the left second branch and bilateral third branches. No interrelationship between the intrahepatic portal flow velocity and the severity of liver cirrhosis and portal hypertension was observed. PMID- 1501370 TI - [Clinical utility of receptor imaging in the assessment of liver function]. AB - Technetium-99m diethylene triamine pentaacetic acid-galactosyl human serum albumin (TcGSA) is a newly developed receptor-binding radiopharmaceutical, specific for the asialoglycoprotein receptor, which resides exclusively on the plasma membrane of hepatocytes. Clinical utility of TcGSA was evaluated in 3 control subjects with normal livers and in 54 patients with various liver diseases. The parameter, Receptor Index, was derived from liver and heart time activity data and is the ratio of radioactivity of the liver over the radioactivity of the liver plus heart at 15 min after the intravenous injection of 3 mg of TcGSA. Receptor concentration ([R]o) was obtained by kinetic analysis of liver and heart time-activity data using pharmacokinetic nonlinear modeling. Values for the Receptor Index and [R]o was statistically different in the control subjects and in patients with mild, moderate, and severe liver diseases. Good correlations were obtained between the Receptor Index, [R]o and conventional liver function tests, such as Child-Turcotte criteria score, prothrombin time, and indocyanine green test. Receptor Index and [R]o were properly estimated even in patients with obstructive jaundice or remarkable portocaval shunt. These data suggest that the receptor imaging as well as its parameters, Receptor Index and [R]o, is a potentially practical and reliable diagnostic method for estimating the functioning hepatocyte mass and for assessing liver function. PMID- 1501371 TI - [Corrosion carcinoma of the esophagus. Report of two cases]. PMID- 1501372 TI - [A case of eosinophilic gastroenteritis with small bowel perforation]. PMID- 1501373 TI - [A case of heterotopic pancreas in the ileum]. PMID- 1501374 TI - [The analysis of p53 on the way of submucosal invasion in superficial type colorectal cancer]. PMID- 1501376 TI - [Transaction of the 79th annual meeting of the Japanese Urological Association]. PMID- 1501377 TI - [Photosensitizers in cancer treatment]. PMID- 1501375 TI - [Experimental ileitis in dogs induced by trinitrobenzenesulfonic acid]. PMID- 1501378 TI - [Prostatic cancer in Japan]. PMID- 1501379 TI - [Oncology: current status and future]. PMID- 1501380 TI - Prognostic indicators in prostatic cancer. AB - For therapeutic decisions it is essential to have an evaluation of the tumor volume and the grade of dedifferentiation. Measurement of PSA gives a good additional guide to the tumor volume and to dissemination of the disease. Investigation of the DNA ploidy values can offer further important information on the aggressiveness of the tumor and be helpful for our understanding of the process of tumor propagation. However, DNA studies can still not be regarded as being standard in the clinical work-up of these patients. They are optional but they have a definite place in the research on prostatic cancer. The various methods to study tumor growth by analysis of the S phase fraction are interesting new contributions but still belong to the research laboratories. When we consider prognostic indicators we have to take into account the biologic character of carcinogenesis. Modern research has shown that the development and the progression of cancer is not an instantaneous and solitary reaction. It is a series of events and a net-work reaction between growth-regulating factors, stimulating and inhibiting, a step-wise alteration of the genome. We must recognize that what we are observing is the condition at the present time, and, of course, the observation must be evaluated together with the whole clinical scenario, the man's age, his general condition etc. But still the series of diagnostic procedures presented here will give a rather solid ground for both our therapeutic decisions and for evaluation of the results of treatment. PMID- 1501381 TI - Radical surgery in prostatic cancer. PMID- 1501382 TI - Conservative renal surgery for renal cell carcinoma. Technique and results of in situ and ex-situ surgery. PMID- 1501383 TI - Some aspects in treatment of superficial bladder cancer. PMID- 1501384 TI - Molecular biology and urological tumors. PMID- 1501385 TI - Measurement techniques in neuro-urology. Definitions and clinical applications. PMID- 1501386 TI - Renal transplantation in Scandinavia. PMID- 1501387 TI - [Micturition control]. PMID- 1501388 TI - [Urinary candidiasis]. PMID- 1501389 TI - [Renal transplantation in Japan]. PMID- 1501390 TI - [Differentiation of male genital organs]. PMID- 1501391 TI - [Fibrinolysis in urological cancer and renal transplantation]. PMID- 1501392 TI - [Function and dysfunction of male accessory genital organs]. PMID- 1501393 TI - [Targeting therapy in urology]. PMID- 1501394 TI - [Urology in the aged society]. PMID- 1501395 TI - [Biological response modifiers and urological cancer]. PMID- 1501396 TI - [Chemosensitivity test in urologic oncology]. PMID- 1501397 TI - [Molecular biology in urology]. PMID- 1501398 TI - [Gynecologic infections and childlessness]. PMID- 1501399 TI - [Obviously pregnant. Interview by Arja Laiho]. PMID- 1501400 TI - [The future, challenges and visions of midwifery activities]. PMID- 1501401 TI - [Maternity and child care education in the jungles of Uganda]. PMID- 1501402 TI - [Annual meeting of the Finnish Federation of Midwives: high level and comprehensive professional skills]. PMID- 1501403 TI - [The menopause--a woman's third life experience]. PMID- 1501404 TI - Thromboxane synthesis and action within the kidney. AB - PGH2 and TxA2 exert their actions via tissue specific, receptor isoforms. PGH2/TxA2-dependent platelet aggregation and contraction of vascular and bronchial smooth muscle and of glomerular mesangial cells occur via receptors linked to activation of phospholipase C. Although PGH2/TxA2 appear to be of little importance in the maintenance of renal function under physiological circumstances, increased renal TxA2 biosynthesis has been documented in a variety of animal models of renal disease and in some clinical disorders (Table 2). The effects of this eicosanoid on renal tissues in vitro and of pharmacological manipulation of TxA2 synthesis and action in vivo suggest that such interventions will provide new drugs for the treatment of human kidney disease. PMID- 1501405 TI - Acute phosphate depletion and in vitro rat proximal tubule injury: protection by glycine and acidosis. AB - The effects of phosphate (PO4) removal from Krebs Henseleit buffer on freshly isolated rat proximal tubules (rPT) were assessed by measuring Ca2+ uptake (nmol/mg protein), cellular adenosine triphosphate (ATP) (nmol/mg), tissue K+ content (nmol/mg) and lactate dehydrogenase (LDH) as an index of cell integrity. Ca2+ uptake increased by 50% in rPT incubated in zero PO4 medium as compared to control (2.6 +/- 0.1 vs. 3.9 +/- 0.19, P less than 0.001) and LDH release increased 2.5-fold from 14.2 +/- 0.6 to 31.6 +/- 1.6%, P less than 0.001. Neither verapamil (200 microM) nor mepacrine (50 microM) reduced Ca2+ uptake or decreased LDH release suggesting that the increased Ca2+ uptake was not occurring through potential operated channels and that phospholipase-induced cell injury was not the cause of increased LDH release. Either glycine (2 mM) or extracellular fluid acidosis (pH 7.06), however, significantly diminished rPT injury and Ca2+ uptake. Specifically, as compared to the increased LDH released in untreated. PO4 depleted rPT, LDH release was diminished significantly by glycine treatment (31.0 +/- 0.9 vs. 15.5 +/- 1.6%, P less than 0.001) or acidosis (30.3 +/- 0.04 vs. 19.2 +/- 0.9%, P less than 0.01). Ca2+ uptake did not increase in glycine treated tubules (2.6 +/- 0.1 vs. 2.8 +/- 0.2 nmol/mg, NS) or in the presence of acidosis (2.6 +/- 0.1 vs. 2.97 +/- 0.17 nmol/mg, NS). ATP concentrations were markedly reduced by PO4 depletion (2.8 +/- 0.2 vs. 4.8 +/- 0.3 nmol/mg, P less than 0.001) and remained at low levels during either acidosis or glycine-induced protection.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1501406 TI - Impaired phagocytosis in chronic renal failure is mediated by secondary hyperparathyroidism. AB - Patients with chronic renal failure (CRF) display impaired phagocytosis by the polymorphonuclear leucocytes (PMNL), and these cells have elevated basal levels of cytosolic calcium ([Ca2+]i) and reduced ATP content. It has been suggested that these changes in PMNL metabolism and function are mediated by the state of secondary hyperparathyroidism of CRF. To examine the role of excess PTH in these derangements of PMNL, we studied [Ca2+]i, ATP and phagocytic ability of PMNL in five groups of rats including: CRF, CRF normocalcemic parathyroidectomized (CRF PTX), CRF and normal animals treated with verapamil (CRF-V), and normal-V, respectively. The level of [Ca2+]i in the PMNL of CRF rats (149 +/- 2.7 nM) was significantly (P less than 0.01) higher and the ATP content (4.2 +/- 0.17 nmol/5 x 10(6) PMNL) significantly lower (P less than 0.01) than in normal (108 +/- 2.4 nM; 9.5 +/- 0.15 nmol/5 x 10(6) PMNL), CRF-PTX (103 +/- 2.9 nM; 9.2 +/- 0.19 nmol/5 x 10(6) PMNL), CRF-V (107 +/- 2.2 nM; 9.0 +/- 0.2 nmol/5 x 10(6) PMNL) and normal-V (106 +/- 1.8 nM; 9.2 +/- 0.2 nmol/5 x 10(6) PMNL), despite sustained elevation in blood PTH in the CRF-V group. Phagocytosis was significantly (P less than 0.01) impaired in CRF animals (5.6 +/- 0.25 micrograms oil/10(7) PMNL/min) but was normal in CRF-PTX (9.3 +/- 0.21 micrograms oil/10(7) PMNL/min) and CRF-V (9.5 +/- 0.22 micrograms oil/10(7) PMNL/min) rats. The values of phagocytosis in normal and normal-V rats were 9.6 +/- 44 and 9.6 +/- 0.18 micrograms oil/10(7) PMNL/min, respectively.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1501407 TI - Culture of endothelial cells from baboon and human glomeruli. AB - Whereas mesangial and epithelial cells from glomeruli are commonly grown in vitro, there has been a failure to isolate and propagate human glomerular capillary endothelial cells. This study defines the conditions for the reproducible isolation and growth of homogeneous monolayers of primate (baboon and human) glomerular capillary endothelial cells. Using selective media and growth factors, the following criteria were identified to optimize the isolation and proliferation of glomerular endothelial cells: (1) collagenase treatment of isolated glomeruli; (2) requirement for 20% serum, endothelial cell growth factor and heparin; (3) requirement of fibronectin as surface matrix; and (4) isolation from donors less than 60 years old, as premature senescence was directly proportional to the age of the human kidney donor. Under these conditions, primary cultures with an endothelial cell composition greater than 70% were reproducibly obtained. Homogeneous endothelial monolayers were developed from 20 of 23 human kidneys, and maintained for 5 to 10 passages, depending on the age of the kidney donor. Purification to homogeneity was achieved by patch cloning or by fluorescence-activated cell sorting. Glomerular capillary endothelial cells exhibited a cobblestone morphology at confluence, expressed factor VIII-related antigen, angiotensin converting enzyme activity, and endocytosed acetylated low density lipoproteins. Electron microscopy revealed the presence of intracellular Weibel-Palade bodies and caveolae and microvillous projections on the luminal surface. Glomerular cells also stained positive for Ulex europaeus, a lectin characteristic of human endothelial cells. In addition, preliminary results indicate that human glomerular endothelial cells increase intracellular cyGMP in response to alpha-human 5 to 28 atrial natriuretic peptide and intracellular free calcium in response to thrombin. PMID- 1501408 TI - Depletion of CD8 positive cells in nephrotoxic serum nephritis of WKY rats. AB - Following a small dose of nephrotoxic serum (NTS) WKY rats demonstrated crescentic glomerulonephritis, which was characterized by the early infiltration of CD8 positive cells in glomeruli. In vivo depletion of CD8 positive cells from WKY rats completely prevented proteinuria (4.6 +/- 4.8 mg/day vs. 105.3 +/- 11.6 mg/day on day 10; N = 19, P less than 0.001) and crescent formation (2.7 +/- 2.9% vs. 94.3 +/- 2.6%; P less than 0.001). Immunofluorescence revealed complete inhibition of the influx of CD8 positive cells and subsequent reduction of the infiltration of macrophages in the glomeruli. Glomerular binding of 125I-anti-rat glomerular basement membrane antibodies, host anti-rabbit IgG production and the C3 level in the circulation were the same as in the control. These data indicate that CD8 positive cells play a key role in glomerular injury and crescent formation. This model provides a useful system for studying the cellular mechanisms that lead to glomerular injury and subsequent crescent formation. PMID- 1501409 TI - Effects of salt restriction on renal growth and glomerular injury in rats with remnant kidneys. AB - Male Munich-Wistar rats underwent right nephrectomy and infarction of two thirds of the left kidney. Rats were randomly assigned to ingest standard chow (REM) or a moderately salt restricted chow (LS). A third group of rats were fed the low salt diet and were injected with an androgen (LSA). Eight weeks after ablation, glomerular volume and glomerular capillary radius were markedly increased in REM. This increase was prevented by the low salt diet, however, the antihypertrophic effect of the diet was overcome by androgen. Values for glomerular volume and capillary radius were similar in LSA and REM. Morphologic studies revealed that approximately 25% of glomeruli were abnormal in REM. Much less injury was observed in salt restricted rats, however, the protective effect of the low salt diet was significantly abrogated when renal growth was stimulated in salt restricted rats by androgen. Micropuncture studies revealed that glomerular pressure was elevated in all three groups and not affected by diet or androgen. Serum cholesterol was also similar in the three groups. These findings indicate that renal and glomerular hypertrophy are correlated with the development of glomerular injury after reduction in renal mass and suggest that dietary salt restriction lessens renal damage, at least in part, by inhibiting compensatory renal growth. PMID- 1501410 TI - Chronic metabolic acidosis accelerates whole body proteolysis and oxidation in awake rats. AB - Previous work has documented an acceleration of proteolysis and branched-chain amino acid oxidation when muscles from rats with chronic metabolic acidosis were incubated in vitro. The present study examines the impact of chronic metabolic acidosis on whole body amino acid turnover and oxidation in chronically catheterized awake male Sprague-Dawley rats using stochastic modeling and a primed continuous infusion of L-[1-14C] leucine. Whole body protein turnover was accelerated by acidosis as reflected in a 70% increase in proteolysis and a 55% increase in protein synthesis. Amino acid oxidation was increased 145% in rats with chronic metabolic acidosis relative to control rats receiving diets identical in protein and calories based on a reciprocal pool model and plasma alpha-ketoisocaproate specific radioactivity. These changes were accompanied by a 104% increase in liver branched-chain ketoacid dehydrogenase (BCKAD) activity in rats with acidosis, similar to previously documented increases in skeletal muscle BCKAD activity caused by acidosis. In contrast, kidney BCKAD activity was decreased 38% by acidosis, illustrating the tissue-specificity of the changes that were present. We conclude that chronic metabolic acidosis accelerates whole body protein turnover and affects the reincorporation of amino acid into body proteins by accelerating amino acid oxidation. PMID- 1501411 TI - Importance of NO/EDRF for glomerular and tubular function: studies in the isolated perfused rat kidney. AB - The effect of the addition of N omega-nitro-L-arginine (L-NNA, 10 and 100 microM) to isolated rat kidneys perfused with a complex medium containing 21 amino acids has been studied. A cyclooxygenase inhibitor was added throughout to block prostaglandin synthesis. L-NNA caused significant reductions in renal perfusion flow rate (PFR, 9.8 +/- 1.4 vs. 15.9 +/- 1.1 ml.min-1.g kidney wt-1, P less than 0.0001), glomerular filtration rate (GFR, 566 +/- 57 vs. 705 +/- 47 microliters.min-1.g kidney wt-1, P less than 0.05) and an increase in the relative filtration fraction (%FF, 7.0 +/- 0.6 vs. 5.2 +/- 0.4%, P less than 0.05) compared to control kidneys. L-NNA perfused kidneys had a lower absolute sodium (72 +/- 9 vs. 88 +/- 4 mumol.min-1.g kidney wt-1, P less than 0.05) and glucose reabsorption (3.5 +/- 0.5 vs. 5.4 +/- 0.4 mumol.min-1.g kidney wt-1, P less than 0.05), corresponding mainly to a lower sodium and glucose filtration. However, the relative reabsorption of sodium and glucose in the presence of L-NNA was attenuated, too (82.8 +/- 2.0 vs. 87.0 +/- 3.3% P less than 0.05 and 91.3 +/- 1.1 vs. 94.1 +/- 0.5%, P less than 0.05). Potassium handling and protein excretion were not changed significantly; fractional protein excretion increased slightly with the addition of L-arginine (47 +/- 5 vs. 55 +/- 7 ng.microliters-1, P less than 0.05). The differences between control and L-NNA treated kidneys (with the exception of differences in FRGluc) could be fully (L-NNA, 10 microM) or partially (L-NNA 100 microns) reversed by adding L-arginine (1 mM) to the perfusion medium. The observed results could be obtained in two different rat strains (Sprague-Dawley and Wistar). Only L-NNA and L-arginine caused the observed changes, while D-NNA and D-arginine were without effect. It is concluded that NO/EDRF is basally released from the isolated perfused rat kidney, and is of importance not only in the regulation of renal hemodynamics but also in the regulation of renal tubular function. PMID- 1501412 TI - Long term effects of morphine on mesangial cell proliferation and matrix synthesis. AB - Since focal glomerulosclerosis is the predominant glomerular lesion in heroin nephropathy and since mesangial expansion is considered to be a precursor of glomerulosclerosis, we have evaluated the effect of opiates on mesangial cell (MC) proliferation and matrix synthesis. We showed, using a fluorometric assay, that MC are not capable of metabolizing heroin to its active metabolite morphine. Cells exposed to morphine (10(-5) M or 10(-4) M) in prolonged cultures either continuously (Group A) or intermittently (Group B) showed enhanced incorporation of [3H]thymidine when compared to control cells (control, 88600 +/- 26303 cpm/well vs. morphine 10(-4) M-Group A, 321203 +/- 52867, P less than 0.001; control vs. morphine 10(-4) M-Group B, 223126 +/- 46866 cpm/well, P less than 0.01; control, 107593 +/- 42284 cpm/well vs. morphine 10(-5) M - Group A, 267108 +/- 41866 cpm/well, P less than 0.001; control vs. morphine 10(-5) M - Group B, 202317 +/- 24325 cpm/well, P less than 0.05). However, MC incubated with a lower concentration of morphine (10(-6) M) enhanced DNA synthesis when exposed intermittently only (control, 107593 +/- 42284 cpm/well vs. Group B, 219164 +/- 15552 cpm/well, P less than 0.05). This growth stimulating effect of morphine (10(-6) M and 10(-5) M) was also observed at earlier time points, that is, one- and one-and-a-half-week old cultures. However, in one-week-old cultures. morphine in a higher concentration (10(-4) M) showed a suppressive effect (P less than 0.05) on MC proliferation (morphine, 3620 +/- 220 cpm/well vs. control, 4668 +/- 410 cpm/well). This effect not only subsided by one and a half weeks but morphine (10(-4) M) treated cells enhanced MC proliferation. An opioid antagonist, naloxone attenuated the effect of morphine in one and half week old cultures. Morphine at 10(-6) M to 10(-4) M concentrations enhanced incorporation of [3H]proline in the extracellular proline pool (a component of mesangial matrix) when compared to control (control, 309661 +/- 3992 vs. morphine 10(-4) M, 363104 +/- 10539 cpm/well, P less than 0.05 or morphine 10(-5) M, 397954 +/- 31008 cpm/well, P less than 0.001 or morphine 10(-6) M, 384630 +/- 26369 cpm/well, P less than 0.01). In addition, MC incubated with morphine (10(-6) M and 10(-4) M) also enhanced (P less than 0.001) synthesis of laminin.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1501413 TI - Direct amphotericin B-mediated tubular toxicity: assessments of selected cytoprotective agents. AB - Amphotericin B (AB) may induce acute renal failure by vasoconstrictive and tubulo toxic effects. Although mannitol, Ca2+ channel blockers, and lipid-based AB preparations have been suggested to mitigate in vivo AB nephrotoxicity, whether they confer direct tubular cytoprotection has not been defined. Therefore, this study assessed the impact of mannitol, verapamil/extracellular Ca2+, and cholesteryl sulfate (CS) AB binding on AB cytotoxicity, employing an isolated rat proximal tubular segment (PTS) preparation. After 30 to 60 minutes of incubation, 0.2 mg/ml of AB (Fungizone) caused marked toxicity, as assessed by LDH release (29 to 44%) and ATP depletion (greater than 90%). Approximately 40% of the LDH release could be attributed to deoxycholate, the standard AB (Fungizone) solubilizing agent. Both 100 mM mannitol and 100 mM glucose decreased AB-mediated LDH release, despite having a quantitatively trivial impact on ATP concentrations (increments of less than or equal to 1% at normal values). Dimethylthiourea (25 mM; equipotent to 100 mM mannitol/glucose as a hydroxyl radical scavenger) did not decrease LDH release. Neither verapamil addition (100 microM) nor Ca2+ removal from the PTS buffer had a protective effect. CS binding completely eliminated AB's toxicity (no LDH or ATP losses). The effect of AB and CS-AB on concomitant O2 deprivation/reoxygenation (30 min/15 min) PTS injury was also assessed. AB and hypoxia/reoxygenation caused additive, not synergistic, LDH release whereas CS-AB had no adverse effect.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1501414 TI - Hydrated clearance of gadolinium-DTPA as a measurement of glomerular filtration rate. AB - Technetium (99mTc)-diethylene triamine pentaacetic acid (DTPA) hydrated clearance studies are accurate for determining GFR but require special facilities for handling and measuring samples. We investigated the potential of a non radioactive paramagnetic analog, Gadolinium (Gd)-diethylene triamine pentaacetic acid (DTPA), an approved NMR contrast agent, as a glomerular filtration marker. Instead of relying on the radioactivity of technetium, this test is based on the fact that gadolinium induces alterations in the NMR T1 relaxation times in blood and urine samples. Ninety patients underwent simultaneous determinations of GFR using 1 mCi of Tc-DTPA and 0.05 mmol/kg Gd-DTPA (Berlex Labs) IV. The patients were hydrated with oral and intravenous fluid. Following a one hour equilibrium period, three or four consecutive urine collections were obtained; plasma samples were acquired at the beginning and end of each approximately 20-minute interval. 99mTc-DTPA radioactivity was determined with a scintillation counter. T1 relaxation times were measured on a 10 MHz NMR spectrometer. These were converted to Gd-DTPA concentration by comparison with standard solutions. The Gd-DTPA derived GFR closely approximated the 99mTc-DTPA derived GFR which ranged from 15 to 147 ml/min. The equation and correlation coefficient of the regression line is y = 1.04 x -2.2, r = 0.94. Thus, Gd-DTPA is a safe, non-radioactive indicator of GFR that may provide an alternative renal clearance method for clinical studies of progressive renal disease and nephrotoxicity. PMID- 1501415 TI - The sodium retaining effects of cyclosporine. AB - The effect of chronic cyclosporine administration on volume regulation was studied in mongrel dogs. Dogs received either cyclosporine (20 mg/kg/day p.o.; N = 7) or vehicle (N = 6) while being maintained on a constant sodium diet. Dogs had measurement of baseline vasoactive hormones. Daily sodium excretion was determined. Following eight days of drug administration, dogs were anesthetized, pre-volume expansion data was collected, and dogs underwent a one hour, 10% body weight 0.9% saline volume expansion. Daily sodium balance was +8.6 +/- 2.2 mEq in the cyclosporine group versus 0.4 +/- 1.8 mEq (P less than 0.05) in the control group after 8 days. Prior to acute volume expansion, aldosterone was 22.5 +/- 7.1 ng% in the cyclosporine group versus 4.7 +/- 0.7 ng% in controls (P less than 0.05). ANF was suppressed in the animals receiving cyclosporine. In response to volume expansion, the cyclosporine group demonstrated an attenuation of maximum urine flow by 56%, fractional excretion of sodium by 52%, and electrolyte free water clearance by 75% when compared to controls (P less than 0.05). We demonstrate that chronic cyclosporine administration activates the renin angiotensin-aldosterone system, suppresses circulating ANF, and results in chronic sodium retention. Additionally, cyclosporine attenuates the natriuretic and diuretic response to acute volume expansion. PMID- 1501416 TI - Childhood membranoproliferative glomerulonephritis type I: limited steroid therapy. AB - Nineteen patients with biopsy proven membranoproliferative glomerulonephritis type I (MPGN I) and a minimum of three years of follow-up (mean 6.5 +/- 0.7 years) have been treated with an uncontrolled regimen of limited corticosteroids. Initial therapy ranged from 20 mg per os (po) every other day to 30 mg/kg/day i.v. for three consecutive days, depending on clinical disease severity. Therapy was then decreased based on each patient's improving clinical status. At diagnosis creatinine clearance (CCr) was less than 80 ml/min/1.73 m2 in 12 patients and less than 50 in 2. All patients had hematuria and proteinuria, with 15 in the nephrotic range. Hypertension, present at diagnosis in 13, developed in five others following institution of prednisone, and was controlled medically. Renal biopsy was repeated after two years of therapy prior to cessation of treatment (mean total treatment duration 38 +/- 3 months). Follow-up biopsy revealed decreased glomerular inflammatory activity in 88% of patients. All patients have now been off prednisone for 40 +/- 9 months. The mean CCr is 126 +/ 5 ml/min/1.73 m2. Eight patients have normal urinalyses. These data suggest that early therapy with a limited course of corticosteroids, and control of associated hypertension, may forestall progressive renal insufficiency in children with MPGN type I. PMID- 1501417 TI - Carnitine metabolism during exercise in patients on chronic hemodialysis. AB - Patients on hemodialysis (HD) have impaired exercise performance. Carnitine homeostasis is also abnormal in this population. As carnitine is an important cofactor for muscle energy metabolism, exercise performance and skeletal muscle carnitine metabolism were characterized in eight HD patients, and in five age matched controls. Each patient underwent graded bicycle exercise testing to define maximal performance, and prolonged exercise at 70% of their peak work capacity. Muscle (vastus lateralis) total carnitine content (carnitine plus all acylcarnitines) at rest was lower in HD patients than in controls (2320 +/- 1190 vs. 3800 +/- 940 nmol/g, P less than 0.05). In patients on HD, muscle carnitine content was inversely correlated to time on HD (r = -0.74, P less than 0.05), and positively correlated to peak exercise performance (r = 0.77, P less than 0.05). In patients on HD, 8 +/- 7% of the muscle carnitine pool at rest was short-chain acylcarnitines (similar to the distribution in controls), but 32 +/- 5% of the plasma carnitine pool consisted of short-chain acylcarnitines. With high intensity exercise in patients on HD, muscle short-chain acylcarnitine content increased from 130 +/- 130 to 1380 +/- 820 nmol/g (P less than 0.01). The change in muscle short-chain acylcarnitine content with exercise was correlated with the increase in muscle lactate content (r = 0.88, P less than 0.01). In summary, patients on HD had a lower muscle total carnitine content than control subjects which was correlated to exercise performance.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1501418 TI - Protein intake and blood glucose as modulators of GFR in hyperfiltering diabetic patients. AB - Glomerular hyperfiltration has been claimed to be a risk factor for the development of diabetic nephropathy. Protein intake and hyperglycemia can both increase GFR in diabetic and normal subjects. Our study was designed to explore the relative importance of short-term changes in protein intake and glycemia on the modulation of renal hemodynamics in insulin-dependent diabetic (IDDM) patients with and without glomerular hyperfiltration. The renal hemodynamic response to a protein challenge was studied in eight hyperfiltering (HF) and eight normofiltering (NF) patients after a three week period of low or normal protein diet (LPD, NPD), each study being conducted twice, in random order, under conditions of prevailing hyperglycemia (H) and euglycemia (E). In HF patients GFR failed to increase significantly in response to protein challenge during NPD under conditions of either H or E (Baseline vs. 2 hr H: 151 +/- 4 vs. 155 +/- 6, NS; E 147 +/- 4 vs. 157 +/- 7 ml/min/1.73 m2, NS). A more normal response was restored following LPD with GFR increasing in all but one patient after challenge during H and in all patients during E (Baseline vs. 2 hr H: 130 +/- 7 vs. 145 +/- 8, P less than 0.07; E: 127 +/- 7 vs. 143 +/- 7 ml/min/1.73 m2, P less than 0.01). Changes in RPF paralleled the changes in GFR and filtration fraction remained stable under all study conditions.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1501419 TI - Immunochemical studies of the Alport antigen. AB - The Alport antigen, a component of normal glomerular basement membranes (GBM) which is absent in Alport familial nephritis, is characterized as a 26 kD non collagenous (NC1) peptide identified by a monoclonal antibody (Mab A7) and an Alport alloantibody. Both antibodies discriminate X-linkage of the Alport defect using indirect immunofluorescence of hemizygous and heterozygous Alport GBM and epidermal basement membrane (EBM). Immunoblotting of SDS-PAGE gels of collagenase digested Alport renal BM shows absence of monomeric and dimeric components of the Alport antigen, alpha 3(IV) NC1, and alpha 4(IV) NC1. By immunoprecipitation experiments with specific antibodies, the Alport antigen is distinct from the 26 kD NC1 peptide derived from alpha 1(IV). The monoclonal antibody to the Alport antigen and rabbit antiserum to a non-consensus sequence of alpha 5(IV) NC1 react similarly by immunofluorescence with normal kidney and both fail to bind to Alport renal BM. Two dimension Western blots of collagenase-digested BM show that the anti-Alport antigen and the ant-alpha 5(IV) NC1 react similarly with monomeric and dimeric components of BM collagen. These studies are consistent with the likelihood that the Alport antigen and alpha 5(IV) NC1 are the same or are highly homologous molecules. The precise relationship will require characterization of alpha 5(IV) NC1 protein and determination of the nucleotide sequence of the Alport antigen. The associated absence of alpha 3(IV) NC1 and alpha 4(IV) (NC1) from Alport BM is consistent with other observations for a molecular association of these chains in a novel collagen network. PMID- 1501420 TI - Expression of a monoclonal antibody (3G5) defined ganglioside antigen in the renal cortex. AB - The monoclonal antibody (mAb) 3G5 was found, by indirect immunofluorescence, to bind to renal cortical structures in frozen sections of human, rat and calf kidneys. Double indirect immunofluorescence studies on frozen sections of rat kidneys showed that 3G5 stained only the glomerulus and the distribution of the 3G5 antigen on the glomerulus was more extensive than the staining observed with antibodies to Factor VIII antigen. 3G5 stained the proximal convoluted tubules and collecting tubules in bovine renal sections but glomeruli did not stain with 3G5. The 3G5 mAb did not stain tissue cultured bovine glomerular endothelial cells or mesangial cells, but did stain bovine glomerular epithelial cell cultures. 3G5 did not stain MDCK cell cultures. The binding of mAb 3G5 to glomeruli was investigated by immunoelectron microscopy of rat renal tissue. In contrast to the podocyte specificity on bovine glomerular cells in vitro, it was found that the specificity of 3G5 expression on rat glomerular cells in vivo was broader. No binding of mAb 3G5 was found outside the glomerulus in the rat renal cortex. Podocytes, endothelial cells and capsular epithelial cells expressed the 3G5 antigen most strongly. A lesser amount of binding was found in the glomerular basement membrane. The mesangium showed a little binding of mAb 3G5 and no binding at all was found to other cortical structures. The 3G5 antigen in rat renal tissue was found to be a glycolipid that migrated between the ganglioside markers GM2 and GM1 by immunostaining of thin layer chromatograms.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1501421 TI - Cervical discs are most susceptible to beta 2-microglobulin amyloid deposition in the vertebral column. AB - Intervertebral discs of 41 chronic renal failure autopsy cases were examined histologically and immunohistochemically to assess the distribution of beta 2 microglobulin-associated (beta 2m) amyloid in the vertebral column. The results demonstrated beta 2m amyloid to appear first in the cervical discs, then in the lumbar and upper thoracic discs, and finally in the middle and lower thoracic discs as the dialysis period is prolonged. The shortest dialysis period for which beta 2m amyloid was detected was one year and seven months. Deposition of beta 2m amyloid was most remarkable in the C4-5, 5-6, and 6-7 levels, which are known to sustain severe mechanical stress in daily life. Thus it is suggested that local mechanical stress accelerates beta 2m amyloidosis. A marked macrophage reaction was observed around the amyloid in cases of severe amyloidosis, the macrophages themselves being immunohistochemically positive for IL-1 beta and TNF-alpha. Amyloid deposition and reactive inflammation mediated by cytokines appear to be closely related to the pathogenesis of destructive spondyloarthropathy. PMID- 1501422 TI - Impaired metabolism of high density lipoprotein in uremic patients. AB - We measured lipoproteins, apolipoproteins, lipoprotein lipase (LPL), hepatic triglyceride lipase (HTGL), lecithin: cholesterol acyltransferase (LCAT) and parameters of calcium metabolism to evaluate the roles of these enzymes and hypertriglyceridemia for impaired high-density lipoprotein (HDL) metabolism in chronic renal failure, and to examine the impact of altered calcium homeostasis on the lipoprotein-regulating enzymes. The subjects were 25 healthy volunteers and 66 uremic patients, 24 treated with hemodialysis (HD) and 42 with continuous ambulatory peritoneal dialysis (CAPD). Lipoprotein analysis revealed: (1) reduction in HDL cholesterol especially in HDL2 subfraction; (2) increase in HDL triglyceride; and (3) decreased ratio of HDL2 cholesterol to HDL3 cholesterol in both HD and CAPD patients. Simple regression analysis showed: (1) a positive correlation between VLDL triglyceride and triglyceride/cholesterol ratio of HDL; (2) positive correlations of LPL level in post-heparin plasma to cholesterol concentrations in HDL2, HDL3 and total HDL, and to apolipoproteins A-I and A-II; and (3) inverse correlations of HTGL to HDL2 cholesterol and to the ratio of HDL2 cholesterol/HDL3 cholesterol. Multiple regression analysis of HDL cholesterol indicated positive association with LPL and inverse correlation with VLDL triglyceride. Four variables including LPL, HTGL, LCAT and VLDL triglyceride explained 51.5% of the variation of HDL cholesterol. HDL2 cholesterol was associated positively with LPL and negatively with VLDL triglyceride in the model. HDL3 cholesterol was associated positively with LPL, HTGL and LCAT and inversely with VLDL triglyceride. Stepwise multiple regression analysis indicated that independent predictors of HTGL were gender, parathyroid hormone levels by a mid-portion assay, ionized calcium and age, and that those of LCAT were ionized calcium and age.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1501423 TI - Treatment of chronic hyponatremia in rats by intravenous saline: comparison of rate versus magnitude of correction. AB - The role of the rate of correction in the development of demyelinating brain lesions after correction of chronic severe hyponatremia is controversial. It has been recently suggested in rats treated by intravenous (i.v.) hypertonic saline (NaCl) that both the rate and the absolute change in serum sodium represent critical risk factors. However, we previously demonstrated in rats treated by intraperitoneal (i.p.) injections of NaCl that below a threshold of serum sodium rise of 20 mEq/liter/24 hr, only 5% of the brain lesions were recorded, even in rats submitted to a rapid (1 hr) serum sodium increment following the i.p. injection. Working below this threshold (serum sodium rise less than 20 mEq/liter/24 hr) in the present work, allowed us to independently determine the role of the rate in the outcome of the correction. This was done by submitting the rats to a rapid (1 hr) intravenous infusion of NaCl. As a difference between the i.p. and i.v. route in the degree of volume expansion produced by the NaCl administration could also play a role in the pathogenesis of the brain lesions, rats treated with rapid i.v. infusion of NaCl (associated with volume expansion) were compared to a group of rats treated with water restriction (associated to volume contraction) to evaluate the role of volemia on the incidence of neurological damage. Hyponatremia was induced over three days with d-glucose in water and vasopressin. The group 1 was corrected by intravenous (i.v.) infusion of hypertonic saline over one hour.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1501424 TI - Anti-DNA antibodies form immune deposits at distinct glomerular and vascular sites. AB - To investigate the capacity of lupus autoAb to produce glomerular immune deposits (ID) and nephritis, 24 murine monoclonal (m) anti-DNA antibodies (Ab), derived from either MRL-lpr/lpr, SNF1 or NZB lupus-prone mice and selected based on properties shared with nephritogenic Ig, were administered i.p. (as hybridomas) and i.v. (as purified Ig) to normal mice; at least four mice/mAb were evaluated. Three general patterns of immune deposit formation (IDF) were observed: extracellular ID within glomeruli (+/- blood vessels, N = 8); intranuclear ID (N = 5); or minimal or no ID (N = 11). The four MRL m anti-DNA Ab that produced significant extracellular ID demonstrated different disease profiles including: (a) mesangial and subendothelial ID with anti-basement membrane staining, associated with proliferative glomerulonephritis, PMN infiltration, and proteinuria; (b) diffuse fine granular mesangial and extraglomerular vascular ID, associated with proliferative glomerulonephritis and proteinuria; (c) dense intramembranous ID and intraluminal ID, associated with capillary wall thickening, mesangial interposition and expansion, aneurysmal dilatation and intraluminal occlusion of glomerular capillary loops, and heavy proteinuria; and (d) mesangial and extraglomerular vascular ID, associated with mild segmental mesangial expansion, without proteinuria. These MRL mAb were derived from four different mice, and they had variable pIs and isotypes. They all cross reacted with multiple autoantigens (autoAg), however, their autoAg binding profiles were distinguishable. Among the SNF1 derived mAb, four produced histologically and clinically indistinguishable disease characterized by diffuse mesangial and capillary wall ID, associated with cellular proliferation/infiltration and proteinuria. Three of the four mAb were derived from the same mouse and were clonally related; they were: IgG2b with SWR allotype, relatively cationic, highly cross reactive with similar Ag binding patterns, idiotypically related and encoded by identical VH and nearly identical VL sequences. We conclude that both the capacity of lupus autoAb to form ID and the location of IDF are dependent on properties unique to individual Ig. The results also indicate that the Ag binding region of the autoAb is influential in this process, and they suggest that multiple Ab-Ag interactions contribute to IDF in individuals with lupus nephritis. Furthermore, these observations raise the possibility that the pathologic and clinical abnormalities resulting from these interactions are influenced by the location of IDF, and that the dominant interaction, in a given individual, may be highly influential in the phenotypic expression of nephritis. PMID- 1501425 TI - An accurate practical method for estimating GFR in clinical studies using a constant subcutaneous infusion. PMID- 1501426 TI - Extraction of protein bound ligands from azotemic sera: comparison of 12 deproteinization methods. PMID- 1501427 TI - Pathogenesis of IgA nephropathy. PMID- 1501428 TI - The assessment of depth of anaesthesia in animals and man. AB - The assessment of the depth of anaesthesia in man has received much attention in recent years, following a number of reports of people being aware during surgery. A range of different measures have been suggested for determining the adequacy of anaesthesia in man, but such a critical assessment is rarely applied to laboratory animals. This article describes the methods used to assess anaesthetic depth in both man and animals, and compares the relative states of knowledge about anaesthetic depth in animals and man. PMID- 1501429 TI - A modified anaesthetic induction chamber for rats. AB - The anaesthetic induction chamber for rats described in this paper has been designed for use in conjunction with a controlled delivery of halothane/O2 mixture and an anaesthetic scavenger system. Using this system rapid induction of anaesthesia is achieved using low levels of anaesthetic vapour without risk to the operator. PMID- 1501430 TI - Developmental and regressive changes in the testes of the Himalayan rabbit. AB - The testes of 81 Himalayan rabbits, controls in toxicity studies, and 113 purpose bred rabbits of various age groups from birth to 2 years were studied. In mature male rabbits, regressive changes in the seminiferous tubules including the multinucleated spermatid giant cells were common and showed a tendency for age related and seasonal differences. The finding is considered as a remnant of the previous seasonal and possibly also social testicular regression in wild living animals. The giant cells develop from the syncytium of the germinative epithelium and have parallels in phylogenesis. PMID- 1501431 TI - The effects of buprenorphine, nalbuphine and butorphanol alone or following halothane anaesthesia on food and water consumption and locomotor movement in rats. AB - Locomotor activity and food and water consumption are potentially indices of post operative pain in laboratory rodents, but it is important to establish whether these variables are directly affected by opioid analgesics or by halothane anaesthesia in normal rats. The effects of three opioids, buprenorphine, nalbuphine and butorphanol administered alone or following halothane anaesthesia, were studied in groups of normal non-operated adult Wistar rats. All 3 analgesics affected food intake and activity levels, but had little or no effect on water intake. Buprenorphine caused a significant elevation of activity levels and a reduction in food intake at clinical doses (0.01 and 0.05 mg/kg s/c). Nalbuphine (0.5, 1 and 2 mg/kg s/c) caused a reduction in food intake but had a smaller stimulatory effect on locomotion. Butorphanol (0.4 mg/kg s/c) caused a reduction in food intake and elevation in activity. These results suggest that water consumption is likely to be a more reliable variable to use when assessing post operative pain and the efficacy of analgesics in rats. PMID- 1501432 TI - Echocardiographic parameters and indices in the normal beagle dog. AB - M-mode and two-dimensional echocardiographic measurements were made from the right sternal border of 50 healthy Beagles (25 males and 25 females) approximately 7 months old. The dogs were conscious and standing during the investigation. The following parameters, in systole and diastole, were measured on the echocardiographic images: left ventricular posterior wall thickness (LVWT); intraventricular septum thickness (IST); left ventricular internal dimension (LVID); and circumference (LVC). Fractional shortening (FS) and ejection fraction (EF) were also calculated. Mean, standard deviation, range and coefficient of variation are reported for each echocardiographic parameter and for body weight. Males and females were considered separately and together. Each parameter was analysed statistically to check for differences between the sexes and for correlations with body weight. A statistically significant difference between the sexes was only observed for LVWT in systole and diastole. A linear regression with body weight was obtained only for LVID in systole and in diastole. The results show that morphofunctional cardiac homogeneity is independent of size in dogs of this breed and age. PMID- 1501433 TI - Anterior cervical microsurgical approach to the cranial base in the rabbit: technical note. AB - Current trends in research on craniofacial syndromes have led to enhanced interest in the cranial base as a contributory factor in the development of normal and abnormal midfacial structure. Indeed, attention has focused upon one particular growth plate in the posterior cranial base, the spheno-occipital synchondrosis, since it has been shown that alterations in this structure are associated with profound changes in craniofacial growth. In this report we describe a surgical approach to the cranial base of the rabbit that is safe, simple and reliable. It is applicable to neonatal as well as adult rabbits. PMID- 1501434 TI - Lymphatic drainage of Listeria monocytogenes and Indian ink inoculated in the peritoneal cavity of the mouse. AB - The lymphatic drainage of the peritoneal cavity has been investigated by intraperitoneal inoculation of an intracellular bacterium (Listeria monocytogenes) and an inert marker (Indian ink). The results reveal that both agents are transported, either after phagocytosis by intraperitoneal macrophages or in suspension in the lymph, towards the cranial sternal lymph nodes (Lymphonodi sternales craniales) of the ventral thoracic lymphocentrum (Lymphocentrum thoracicum ventrale) and to the lymph nodes of the mediastinal lymphocentrum (Lymphocentrum mediastinale), prior to systemic dissemination. This mechanism of peritoneal lymph drainage has relevance on experimental studies involving the inoculation of pathogens, and on the investigation of metastatic diffusion of neoplasms from the peritoneum. PMID- 1501435 TI - The effects of intracage ventilation on microenvironmental conditions in filter top cages. AB - Filter-top cages, while effective in reducing cross contamination by particulate material including microbes, can also cause accumulation of the waste gases carbon dioxide and ammonia as well as increased intracage relative humidity. A prototype system which provided each cage with 23 air changes per hour through a nozzle inserted in the filter lid was evaluated. The ventilated cageing system was effective in reducing intracage carbon dioxide, ammonia and relative humidity levels. Mean weekly carbon dioxide levels were 2900 ppm lower, ammonia levels 240 ppm lower and intracage relative humidity levels 8% lower in the ventilated cages than in unventilated controls. PMID- 1501436 TI - A fast and simple technique for jugular catheterization in adult sows. AB - Obtaining measures of an animal's physiological state with minimum disturbance to the animal is essential in animal welfare studies and it is also ethically desirable. A simple technique for implanting a temporary jugular catheter in adult sows is described. The technique involves implantation via an ear vein and can be performed in 5-7 min. Local but not general anaesthetic is required. The technique has no effect on basal levels of salivary cortisol 1-2 h later, suggesting that it has no long term stress consequences. Catheters continue to function perfectly well after 4 h. PMID- 1501437 TI - Haematological and serum biochemical values in hairless and haired descendants of Mexican hairless dogs. AB - Haematological and serum biochemical measurements were carried out in 1-year-old hairless and haired hybrids derived from the Mexican hairless dog (MHD). These hybrids included F1 hybrids obtained from male MHD and female Beagles, and BCF1 hybrids obtained from male hairless F1 and female Beagles. There were no significant differences between F1 and BCF1 hybrids, nor between male and female hybrids. Except for red blood cell counts, haemoglobin concentrations and packed cell volumes which were slightly higher in MHD-descendants than in Beagles, there were no differences for haematological and serum biochemical findings between hairless and haired hybrids when compared to age-matched Beagles. PMID- 1501438 TI - Rabbit encephalitozoonosis in Kenya. AB - Encephalitozoon cuniculi infection was diagnosed in a laboratory rabbit breeding colony at Muguga, Kenya. This is the first report of the disease in rabbits in Kenya. Post-mortem examination showed gross renal lesions and the presence of the parasite in histological sections of the cerebrum and cerebellum. On Gram stain, spores were observed in the kidney sections. PMID- 1501439 TI - Magnetic resonance imaging using a clinical whole body system: an introduction to a useful technique in small animal experiments. AB - A clinical whole body magnetic resonance imaging (MRI) system with high resolution coils was used to obtain non-invasive images of the living rat. The results demonstrate the feasibility of the set-up and the advantages of this new imaging technique: detailed information, no extra costs, longitudinal studies without killing animals and simple anaesthesia. It is concluded that in small animal experimentation, this use of high resolution coils in whole body magnetic resonance systems may be particularly helpful in establishing effects of experimental procedures. Whenever non-invasive visualization is required, especially in longitudinal animal studies, e.g. biomaterial research or tumour investigation, this use of MRI will offer challenging possibilities. PMID- 1501440 TI - Pygomelia in a C3H/Crl mouse: case report. AB - Accessory hind limbs (pygomelia) were found in a male pup born in our colony of C3H/Crl mice. This malformation has not previously been reported in mice. PMID- 1501441 TI - Tumor infiltrating cells. PMID- 1501442 TI - Alterations in tubular epithelial cell adhesion and mechanisms of acute renal failure. PMID- 1501443 TI - Tumor infiltrating cells in human cancer. On the possible role of CD16+ macrophages in antitumor cytotoxicity. AB - BACKGROUND: To obtain a better understanding of the mechanism underlying different modalities of immunotherapy, we investigated the types of tumor infiltrating cells present at the tumor site, with special attention to the presence of macrophages. EXPERIMENTAL DESIGN: Frozen sections of carcinomas of the kidney, colon, breast, lung, ovary, and thyroid gland, as well as malignant melanoma were investigated with a panel of monoclonal antibodies against macrophage, T cell and NK cell associated antigens. Both type and pattern of the tumor-infiltrating cells were analyzed. RESULTS: All tumor-infiltrating cells accumulated preferentially in the stromal bands between tumor cells. In all types of tumor, CD11c+, CD14+, CD68+ and alpha-naphthyl-acetate-esterase positive monocytes/macrophages accounted for most tumor-infiltrating cells. Next in frequency were T lymphocytes (CD2+, CD3+, TCR alpha beta +). Only a few B lymphocytes (CD22+), and T cells expressing the T cell receptor gamma delta (TCR gamma delta) were found. Hardly any lymphoid cells with an NK phenotype (CD3-, CD56+) were present in the tumors studied. Large numbers of CD16+ cells were found, which could be identified as macrophages on the basis of their morphology, positive staining with a panel of monocyte/macrophage markers, and the results of double staining with CD11c. CONCLUSIONS: We have demonstrated the presence of a large number of macrophages in the cellular infiltrates of several types of tumors. The largest numbers of CD16+ macrophages were found in renal cancer, melanoma, and colonic-carcinoma. These are the tumors that are most susceptible to immunotherapy with lymphokine activated killer cells, suggesting that these CD16+ macrophages may be involved in antitumor cytotoxicity. Furthermore, these findings suggest that new strategies of immunotherapy aimed at the use of macrophages present in many tumors could be developed. PMID- 1501444 TI - Glomerular localization of nephritogenic protein complexes on a nonimmunologic basis. AB - BACKGROUND: In a preliminary study, we have found that a group of charge-distinct protein molecules can react with each other to form protein complexes in vitro. The present study was conducted to determine the nephritogenic effect and the mode of action of these proteins in vivo. EXPERIMENTAL DESIGN: To demonstrate the precipitating interactions, a phosphorylcholine (PC)-conjugated, cationized bovine serum albumin (BSA(+)-PC) was applied to react with dinitrophenyl (DNP) protein conjugates by double diffusion test. The types of forces involved in binding actions were determined. The experimental groups of CDF1 mice were injected simultaneously with BSA(+)-PC and individual DNP-protein conjugates through the tail vein. Both clearance kinetics and renal tissue studies were performed. RESULTS: BSA(+)-PC was able to form precipitin lines with respective DNP-protein conjugates in the agarose gel without any antigen-antibody interactions. These precipitating reactions were partially prevented by the presence of either NaCl, urea, or trifluoroacetate, suggesting that electrostatic force, hydrogen bond, and/or hydrophobic force are involved in the precipitation of these modified protein molecules. The clearance kinetics of BSA(+)-PC/BSA-DNP, and BSA(+)-PC/DNP-apoferritin showed a significant acceleration of the rapid phase of elimination. All of the experimental mice had hematuria and systemic thrombotic microangiopathic changes 1 hour later. By immunofluorescence, both the BSA(+)-PC and the DNP-protein conjugate injected were present in the renal glomerular tufts of experimental groups, although these protein molecules failed to deposit in the glomerulus when injected alone. Concomitant fibrinogen deposition was noted in almost all of the glomeruli affected. Moreover, 10 to 50% of the glomeruli examined 4 hours after injection had deposition of the third component of complement (C3). CONCLUSIONS: These data strongly support a hypothesis that nondeposited nephritogenic protein molecules in a fashion of heterogeneous complexes can localize in the glomerulus, thereby initiating renal injury, with the lack of antibody involvement. PMID- 1501445 TI - Impaired attachment of hepatocytes to extracellular matrix components after chronic ethanol administration. AB - BACKGROUND: Previous studies have shown that the assembly and properties of the hepatocyte plasma membrane are altered by ethanol administration, indicating possible changes in the receptor-mediated binding of the plasma membrane to extracellular matrix substrates. In the present study, the effects of chronic ethanol consumption on the ability of hepatocytes to attach to various components of the extracellular matrix were investigated. EXPERIMENTAL DESIGN: Rats were pair-fed for 5 weeks with a liquid diet containing either ethanol (as 36% of total calories) or isocaloric carbohydrate. The effects of ethanol treatment on hepatocyte-extracellular matrix interactions was ascertained by determining the ability of isolated hepatocytes to attach to various extracellular matrix substrates. RESULTS: The attachment of hepatocytes, isolated from the ethanol-fed rats, to laminin-coated plates was significantly decreased compared with hepatocytes from chow-fed or pair-fed controls. Greater decreases in attachment were seen when higher numbers of hepatocytes were seeded in the plates. Similar inhibitions of attachment were also observed when fibronectin or type I collagen were used as matrices. Time-course cell attachment assays indicated that the maximum extent of attachment rather than the rate of attachment was primarily altered by chronic ethanol feeding. Hepatocytes from the ethanol-fed rats also detached more readily from the matrix-coated plates than those from the controls. A reduced number of functional surface receptors for matrix components is likely the most important factor that accounts for the ethanol-induced impairment of hepatocyte attachment. CONCLUSIONS: These results indicate that chronic ethanol administration impairs the interactions of hepatocytes with their extracellular matrix and that this defect could lead to alterations of hepatocyte structure and function. PMID- 1501446 TI - Role of intercellular junctions in the passage of horseradish peroxidase across aortic endothelium. AB - BACKGROUND: The manner in which molecules are transported across the arterial endothelial layer has been a subject open to much interpretation and controversy. Further elucidation and clarification of these mechanisms are of primary interest. EXPERIMENTAL DESIGN: To investigate the ultrastructural features of arterial endothelial junctions and to evaluate their functional roles as a transendothelial pathway for macromolecular transport, experiments were performed on the thoracic aortae of adult male Sprague-Dawley rats by using the ultrathin serial sectioning technique and horseradish peroxidase (HRP). The aorta was perfusion-fixed with or without prior intravenous injection of HRP. RESULTS: The intercellular clefts exhibited a great deal of variety in shape, being linear, winding, interdigitated, irregular and/or dumbbell-shaped in appearance. Besides the typical 20-nm width encountered at the uniform region of intercellular clefts, local widenings (up to several hundred nm) were quite common. The arterial endothelial junctions were highly organized. Junctional elements, including tight junctions and gap junctions, were frequently present in the same intercellular cleft, even on the same plane of sectioning. Sometimes, gap junctions were found without tight junctions, but the intercellular clefts were rarely obliterated by tight junctions alone. Some intercellular clefts were not obliterated by either gap or tight junctions, and HRP was found to reach the subendothelial space by passing through these junctionless clefts. Densitometric determination of the HRP concentration profile in such junctionless clefts showed a decreasing gradient from the luminal to the abluminal front. The serial sections provided evidence that the apparently free vesicles were actually plasmalemmal membrane invaginations open to the luminal or abluminal front in the arterial endothelium. CONCLUSIONS: The present study showed that the junctionless normal endothelial clefts, in addition to the transiently open junctions surrounding mitotic cells, might provide a significant pathway in the transendothelial transport of macromolecules with the size of HRP. PMID- 1501447 TI - Endothelin. Immunohistologic localization in aorta and biosynthesis by cultured human aortic endothelial cells. AB - BACKGROUND: Endothelin-1 (ET-1) has been shown to exist in many organs and to have various biologic functions including vasoconstriction. However, an exact location of ET gene expression of the tissues is not fully investigated. Human aortic tissue was examined to elucidate the exact location of ET gene expression. EXPERIMENTAL DESIGN: Human aortas were obtained at autopsy and fixed in either conventional 10% formalin or 3% paraformaldehyde. The aortic thin sections were subjected to examinations of an immunohistochemistry and in situ hybridization of ET-1. Human aortic endothelial cells were cultured by a previously reported method. ET-1 released in the supernatant from the cultured endothelial cells was radioimmunoassayed. RESULTS: Immunohistologic study of ET-1 revealed a linear staining of the endothelial monolayer and diffuse staining in the intimal and medial smooth muscle cells on human aorta except for fetal aorta. In situ hybridization signals were intense in the endothelial cells from the elderly as well as younger subjects as examined with 35S-labeled anti-sense probe RNA. Fetal aortic endothelial cells revealed the least signals that meant developing but still immature gene translation. Smooth muscle cells showed positive but weak in situ hybridization signals. Control immunohistologic and hybridization studies were negative. ET-1 biosynthesis by cultured human aortic endothelial cells was invariably low in the subjects under the age of 50, ranging from 0.23 to 0.40 pmol/1 x 10(5) cells for 3 days. On the other hand, endothelial cells from the elderly subjects generally synthesized a greater amount of endothelin in vitro. CONCLUSIONS: These findings indicate that ET-1 is most highly expressed in endothelial cells, although not as highly but certainly, expressed in intimal and medial smooth muscle cells. This fact gives a new insight into the biophysiologic and pathologic roles of ET. In addition, these methods are applicable to investigate the gene expression of ET-1 in all organs and tissues. PMID- 1501448 TI - Expression of syndecan in transformed mouse keratinocytes. AB - BACKGROUND: Malignant transformation is frequently associated with altered behavior of cells, a phenomenon that also suggests changes in cell-matrix interactions. We have studied expression of syndecan, a cell surface proteoglycan that binds extracellular matrix components and growth factors, in various chemically transformed mouse keratinocyte cell lines that differ in their morphology and tumorigenicity. EXPERIMENTAL DESIGN: A monoclonal antibody, specific for mouse syndecan, and a cDNA clone for mouse syndecan, were used to detect syndecan in seven different keratinocyte cell lines. The glycosaminoglycan composition of syndecan was studied using differential digestions of heparan sulfate and chondroitin sulfate chains. RESULTS: In general, the tumorigenic cells were found to express lower amounts of syndecan, both at protein and mRNA levels, than the nontumorigenic cells. The most tumorigenic cell line CarC revealed barely detectable syndecan expression. Also, molecular polymorphism of syndecan was observed, as three forms of syndecan with different molecular weights appeared on the surfaces of different keratinocytes. The highly tumorigenic cells, that expressed low amounts of syndecan, expressed syndecan with the largest molecular weight. The different molecular weights were shown to reflect an increased amount of both heparan and chondroitin sulfate chains attached to the core protein. An increased shedding of syndecan ectodomain from the membrane-associated domain was observed in cells that express high amounts of mutated Ha-ras p21. CONCLUSIONS: The results suggest, that transformed epithelial cells can modulate the appearance of syndecan on the cell-surface by at least two ways: (a) by altering its glycosylation or (b) by increasing its shedding from the cell surface. These modulations, together with overall suppression of syndecan expression, could be associated with malignant transformation of keratinocytes. PMID- 1501449 TI - Ploidy independence of Ag-NOR number in neuroblastoma. AB - BACKGROUND: Ag-NOR number and ploidy have potential use in predicting prognosis in malignancy. The issue of independence has not been conclusively studied. In contrast to other malignancies in neuroblastoma poor outcome is linked to diploidy, allowing independent analysis of the reaction of Ag-NOR status to outcome. EXPERIMENTAL DESIGN: A consecutive unselected series of 20 pediatric neuroblastoma patients was used to study the relation between ploidy and mean Ag NOR number per nucleus. Ploidy was established by flow cytometric analysis of nuclear suspensions prepared from Formalin fixed and paraffin embedded tissue. The mean number of Ag-NORs per nucleus was determined using 3-microns paraffin sections, silver staining methods and quantification procedures detailed in the literature. RESULTS: The seven diploid lesions were found to have a mean Ag-NOR number per nucleus of 4.38 (range 0.86-7.5). The 13 aneuploid lesions were found to have a mean Ag-NOR number per nucleus of 2.31 (range 1.17-4.44). Probability of difference (Wilcoxon's two-tailed rank sum test) was greater than 99%. Nonsurvivors (6 of 10 diploid) had mean Ag-NOR number per nucleus of 4.34 (range 2.24-7.5). Survivors (9 of 10 aneuploid) had mean Ag-NOR number per nucleus of 1.73 (range 0.86-2.56). Probability of difference (Wilcoxon's two-tailed rank sum test) was greater than 99%. In aneuploid lesions (n = 13) a negative correlation exists between DNA index and mean number of Ag-NORs per nucleus (correlation coefficient 0.84, slope -0.74, probability of noncorrelation less than 0.010). CONCLUSIONS: The present observations offer the first independent support to the theory that Ag-NOR number is an independent variable to DNA ploidy based on the unique feature of neuroblastoma that diploid lesions have an established poorer prognosis than aneuploid lesion. The observations, although the number of cases is too limited for independent analysis, confirm previously published, strong negative relations between mean Ag-NOR number per cell and survival in childhood neuroblastoma. This relation is similar to findings in other solid tumor lesions. PMID- 1501451 TI - Medicare fraud and abuse anti-kickback safe harbor regulations: where do we go from here? PMID- 1501450 TI - Improved accuracy in diagnostic immunohistochemistry, lectin histochemistry and in situ hybridization using a gold-labeled horseradish peroxidase antibody and silver intensification. AB - BACKGROUND: Improvements in the use of the avidin-biotin peroxidase complex technique and direct as well as indirect labeled avidin-biotin methods for application in diagnostic immunohistochemistry, lectin histochemistry and in situ hybridization are reported. The new technology combines the advantages of immunoenzyme and immunogold silver staining techniques and can be performed on routinely fixed and paraffin-embedded tissues. EXPERIMENTAL DESIGN: The basic modification of the labeling procedures was introduced at the final revealing step. The histochemical visualization of catalytic activity of horseradish peroxidase by the diaminobenzidine reaction was replaced by the detection of horseradish peroxidase immunoreactivity using anti-horseradish peroxidase-gold complexes and their intensification with silver acetate which is relatively light insensitive. RESULTS: The use of gold-labeled anti-horseradish peroxidase antibodies eliminates the need for quenching of endogenous peroxidase activity. Furthermore, the immunogold silver staining provides improved lateral resolution, higher contrast, and lower background staining as compared with the diaminobenzidine reaction. The new technology has been applied for the localization of different polypeptides in endocrine cells, cytoskeletal elements, cell surface receptors, basal lamina type IV collagen, endothelial cell marker, lectin binding sites, and DNA of various viruses. CONCLUSIONS: We concluded that the anti-horseradish peroxidase-gold complex is of general use in a variety of techniques applying horseradish peroxidase as a marker and should be a valuable alternative to existing enzyme substrate techniques. PMID- 1501452 TI - Medicine in 1992: past, present and future. PMID- 1501453 TI - Do doctors control the cost of medical care? PMID- 1501454 TI - House Bill 4244. PMID- 1501455 TI - A death attributed solely to diltiazem. AB - An elderly woman, distraught over the recent death of her husband, was found dead of an apparent suicide. Qualitative screening detected only the presence of diltiazem, an antihypertensive, antianginal agent that was prescribed for a known heart ailment. Quantitation of diltiazem was carried out on available fluids and tissues with the following results: blood 6.7 mg/L, urine 5.4 mg/L, vitreous 5.5 mg/L, and liver 79 mg/kg. Death was subsequently attributed to an overdose of this medication. PMID- 1501456 TI - Two fatalities from ingestion of acetonitrile: limited specificity of analysis by headspace gas chromatography. AB - A married couple was found dead in bed at their home, and the police investigation indicated that they might have ingested methanol and/or ethanol the previous evening. Postmortem examinations were performed and samples of femoral vein blood, urine, and stomach contents were submitted for toxicological analysis. Headspace gas chromatography (HSGC) using two different column packings (Carbopak B and Carbopak C) was used for qualitative and quantitative analysis of organic volatile substances. The apparent concentrations of ethanol in blood and urine were 0.20 and 0.27 g% w/v, respectively. On reanalysis of body fluids by another HSGC method and gas chromatography/mass spectrometry (GC/MS), the presence of ethanol was not confirmed. Instead, acetonitrile was identified at concentrations of 0.8 g/L in blood, 1.0 g/L in urine, and 1.3 g/L in stomach contents. Inorganic cyanide, the toxic metabolite of acetonitrile, was identified in blood from both victims at concentrations of 2.4 micrograms/g (female) and 4.5 micrograms/g (male). Despite the use of two different column packing materials for HSGC, acetonitrile was mistakenly identified as ethanol. PMID- 1501457 TI - Evaluation of phencyclidine by EMIT d.a.u. utilizing the ETS analyzer and a 25 ng/mL cutoff. AB - This study evaluates the usefulness of the EMIT d.a.u. phencyclidine assay using the Syva ETS instrument to reliably detect phencyclidine in urine specimens at 25 ng/mL and above. More than 1600 urine specimens were screened over a one-month period. Fifty three (53) specimens screened positive (25 of these were previously tested positive by EMIT and GC/MS at or above the 25-ng/ml level and resubmitted as unknowns). Of the 53 specimens, 52 were confirmed positive by GC/MS. Reanalysis by EMIT of the one sample that was confirmed negative by GC/MS yielded a negative result. The absorbance difference between a negative sample and a sample containing 25 ng/mL of phencyclidine averaged 53 absorbance units with a standard deviation of 7.7 units. The absorbance difference between a negative sample and a sample containing 75 ng/mL of phencyclidine averaged 105 absorbance units with a standard deviation of 6.8 units. PMID- 1501458 TI - A procedure for eliminating interferences from ephedrine and related compounds in the GC/MS analysis of amphetamine and methamphetamine. PMID- 1501459 TI - Cocaine and some of its products in hair by RIA and GC/MS. AB - Noncomminuted hair samplings (100 mg) from 132 individuals were analyzed for cocaine products by both RIA and GC/MS with D3 internal standards and selected ions for cocaine, benzoylecgonine, and methylecgonine. Ethanol and pH 7 buffer washing until the washes were negative by RIA or GC/MS were followed by overnight digestion in warm 0.1M HCI. A small portion of digest buffered to pH 7 was analyzed by RIA. The remainder, internally standardized, buffered extract was TMS derivatized and analyzed on a capillary OV-1 column by GC/MS. Of the 132 specimens, 10 were positive by RIA and positive by GC/MS for cocaine only, while another 20 specimens were positive for both cocaine and benzoylecgonine by GC/MS as well as positive by RIA. One specimen that was positive by RIA was positive for cocaine and methylecgonine by GC/MS; an additional one was positive for cocaine, methylecgonine, and benzoylecgonine and positive by RIA. The RIA used (100x more reactive to cocaine than to benzoylecgonine) gave positive test results for an additional 47 of the 132 hair samples. Cutoffs used for the RIA were equivalent to 2 micrograms benzoylecgonine or 0.04 micrograms cocaine/g hair, and for GC/MS, cutoffs per gram hair were 0.1 micrograms cocaine and 0.2 micrograms benzoylecgonine or methylecgonine. Relationships between RIA and GC/MS results and distribution of values found are discussed, as are factors that appear to affect recovery from the hair. PMID- 1501460 TI - Preliminary evaluation of the Abbott TDx for screening of D-methamphetamine in whole blood specimens. AB - The Abbott TDx Urine Amphetamine/Methamphetamine II fluorescence polarization immunoassay technique was applied to the determination of D-methamphetamine in hemolyzed whole blood. The assay was found to have 100% cross-reactivity with D methamphetamine and only an 8% cross-reactivity with L-methamphetamine. Whole blood was fortified with D-methamphetamine at concentrations ranging from 25 to 1000 ng/mL. These whole blood calibrators were used to evaluate the following sample preparation techniques: direct, diluted and buffer, and precipitated using methanol, acetone, sulfosalicylic acid, trichloroacetic acid, and zinc sulfate. Calibrators and samples were prepared by mixing 200 microL of whole blood and 200 microL precipitation reagent and centrifuging at 10,000 rpm for 5 min (9600 x g). A 50-microL aliquot of the supernatant was used for the assay. Using the zinc sulfate precipitation, blood calibration curves showed a linear range of 25-1000 ng/mL. The within-run precision for the 25-, 60-, and 200-ng/mL D-methamphetamine blood controls showed percent coefficients of variation of 17.8, 17.0, and 5.4, respectively. The TDx results were compared to RIA and GC/MS assays for the methamphetamine controls and for eight positive case specimens and found reliable for the screening of hemolyzed whole blood. PMID- 1501461 TI - Evaluation of the Syva ETS-PLUS Ethyl Alcohol Assay with application to the analysis of antemortem whole blood, routine postmortem specimens, and synovial fluid. AB - A critical evaluation of the ETS-PLUS Ethyl Alcohol Assay indicates that it is simple to perform, sensitive enough to reliably detect ethanol above a concentration of 0.010 g/dL, and dynamic enough to reliably quantitate ethanol concentrations between 0.010 and 0.400 g/dL, correlating well with headspace gas chromatography. The technique is suitable for the analysis of relatively fresh (less than 1 month old) serum, plasma, urine, bile, vitreous humor, and gastric samples. With the aid of dilution, it is adaptable to the analysis of whole blood, relatively old specimens (more than 3 months old), viscous and highly pigmented plasma, bile, and the occasional extremely viscous vitreous humor specimens. Our evaluation further indicates that samples can remain in the system's covered sample wheel for up to 2 h without significant (less than 10%) diminution in ethanol concentration. This technique was further utilized to evaluate the suitability of synovial fluid as an alternative for vitreous humor. PMID- 1501462 TI - Nonparametric assessment of toxicologic assay linearity by bootstrap analysis. AB - An important aspect in the evaluation of toxicologic assay methodology is the assessment of calibration. This paper presents a new approach for validating calibration using bootstrap analysis. The technique is illustrated with a quantitative assay for benzoylecgonine in urine by gas chromatography/mass spectrometry (GC/MS). Because the bootstrap analysis does not rely on parametric assumptions regarding the distribution of errors about the regression line, it can be applied to situations where the parametric distribution of response errors about the regression line is unknown. This application of bootstrap methodology yields a probabilistic measure of confidence on the linearity of the calibration curve. PMID- 1501463 TI - Alcohol-specific cocaine metabolites in serum and urine of hospitalized patients. AB - The serum and urine from 44 consecutive patients that tested positive for the cocaine metabolite benzoylecgonine (BE) were examined for free cocaine, ecgonine methyl ester (EME), and other metabolites by gas chromatography/ion trap mass spectrometry (GC/MS). In 13 of these patients, unique ethanol-related cocaine metabolites, cocaethylene and ecognine ethyl ester (EEE), were detected in urine and serum. One was from a newborn baby whose mother's blood was positive for cocaine and negative for cocaethylene. In two other patients, isopropanol was also consumed with cocaine and ethanol. In one of these two, cocaisopropylene and ecognine isopropyl ester (EPE) were identified in urine. The urine ethanol concentration in 7 of the 13 cocaethylene-positive patients ranged from 19 to 322 mg/dL. In the other six, ethanol was not detected in the urine. However, each of these latter patients had either prior serum results that were positive for ethanol or admitted to recent alcohol abuse. In the remaining 31 of 44 cocaine positive patients, ethanol and the alcohol-specific cocaine metabolites were absent. The detection of alcohol-related cocaine metabolites is fairly common in a cocaine-positive patient population. PMID- 1501464 TI - Identification of methamphetamines and over-the-counter sympathometic amines by full-scan GC-ion trap MS with electron impact and chemical ionization. AB - An underivatized methane chemical ionization (CI) assay for measuring amphetamines in urine was evaluated against derivatized electron impact (EI) assays using a gas chromatograph-ion trap mass spectrometer. The full-scan CI mass spectra of methamphetamine, ephedrine/pseudoephedrine, and phentermine were compared with the full scan and three-ion EI mass spectra of heptafluorobutyric anhydride (HFBA) and 4-carbethoxyhexafluorobutyryl chloride (CB) derivatives. The fragmentation patterns for these compounds were nearly identical for the three major high molecular weight ions (m/z 254, 210, and 169 for EI-HFBA derivatives, and m/z 308, 262, and 280 for EI-CB derivatives). The CI mass spectra of the underivatized drugs contained more discernible differences at the higher molecular weights, including m/z 119, 148, and 150 for methamphetamine, 148, 166, and 176 for ephedrine/pseudoephedrine, and 91, 133, and 150 for phentermine. The within-run precision ranged from 7-9% for CI versus 5-6% for EI with HFBA derivatization (mean 500 ng/mL, n = 5). The limits of detection (LOD) for amphetamine and methamphetamine were 2.4 and 8.6 ng/mL, respectively, for CI versus 0.7 and 1.4 ng/mL for EI. The limits of quantitation (LOQ) were 4.5 and 19.1 ng/mL for CI versus 1.4 and 5.7 ng/mL for EI. The use of full-scan mass spectral analysis with either electron impact or chemical ionization provides additional qualitative data that may be helpful for measuring methamphetamine in the presence of other sympathomimetic amines. PMID- 1501465 TI - A possible association between fluoxetine use and suicide. AB - Fluoxetine has been available for use as an antidepressant since early 1988. Numerous reports have indicated that it is at least as good as some of the tricyclic antidepressants and that it does not produce as serious toxicity as the tricyclics. Recently, however, case reports have suggested that it may produce suicidal tendencies in some patients. The present report provides data from a medical examiner's office regarding the number of cases in which fluoxetine has been detected and the proportion certified as suicides. PMID- 1501466 TI - Urinalysis of alpha-hydroxyalprazolam, alpha-hydroxytriazolam, and other benzodiazepine compounds by GC/EIMS. AB - This procedure was developed as an overall benzodiazepine confirmation scheme and includes the detection of the most important urinary analytes encountered by clinical toxicology laboratories in North America: alpha-hydroxyalprazolam, alpha hydroxytriazolam, 2-hydroxyethylflurazepam, oxazepam, temazepam, and lorazepam. Desmethyldiazepam (nordiazepam) was not targeted because it is metabolized to oxazepam. This procedure takes advantage of beta-glucuronidase hydrolysis for analysis of intact benzodiazepine molecules, oxazepam-2H5 as an internal standard, a newly developed extraction solvent, and a silylating moiety that may be more sensitive than trimethylsilyl (-TMS) derivatives, the tertbutyldimethylsilyl (-TBDMS) derivative. For all compounds the extraction efficiency was greater than 90% and the limit of quantitation (LOQ at a S/N of 10) was less than 10 ng/mL. Coefficients of variation for a 200-ng/mL control were less than 5% and less than or equal to 11% for within-run and between-run trials, respectively. Of 13 human specimens screened by EMIT and most with self reported histories, alpha-hydroxyalprazolam was found in seven (range 49-1264 ng/mL), oxazepam was found in five (72-3897 ng/mL), and lorazepam (476 ng/mL), 2 hydroxyethylflurazepam (2301 ng/mL), and alpha-hydroxytriazolam (106 ng/mL) in one each. PMID- 1501467 TI - Forensic drug testing for opiates. IV. Analytical sensitivity, specificity, and accuracy of commercial urine opiate immunoassays. AB - Four commercial immunoassays, TDx Opiates (TDx), Coat-A-Count Morphine in Urine (CAC), Abuscreen Radioimmunoassay for Morphine (ABUS) and Emit d.a.u. Opiate Assay (EMIT), were tested for sensitivity, specificity, and accuracy with urine specimens containing known amounts of opiates and opiate metabolites. The immunoassays were evaluated in a semiquantitative mode by comparison of morphine equivalents to GC/MS assay of free and total morphine and codeine or to target concentrations. In all cases, the apparent sensitivities of the assays were higher than those required for detection of morphine at cutoffs mandated by the Health and Human Services guidelines for testing of Federal workers. The apparent specificities of the immunoassays varied considerably. The CAC assay was found to be highly selective for free morphine, whereas TDx, ABUS, and EMIT demonstrated broad cross-reactivity with other opiates. Comparison of semiquantitative results from the immunoassays with GC/MS data indicated a high degree of accuracy for determination of morphine levels. Generally, the patterns of sensitivity and cross-reactivity were unique for each assay, indicating that a detailed knowledge of assay performance characteristics is necessary for accurate interpretation of forensic urine testing data. PMID- 1501468 TI - Biological fate of sulfur mustard, 1,1'-thiobis(2-chloroethane). Urinary excretion profiles of hydrolysis products and beta-lyase metabolites of sulfur mustard after cutaneous application in rats. AB - The urinary excretion profiles of some metabolites of sulfur mustard were determined by gas chromatography/mass spectrometry after cutaneous application of sulfur mustard in rats. Excretion profiles of the individual metabolites thiodiglycol and thiodiglycol sulfoxide, derived from the hydrolysis of sulfur mustard, were determined in different groups of three rats. Concentrations of thiodiglycol detected increased up to 10 fold after treatment of the urine with hydrochloric acid, presumably because of the excretion of acid-labile esters of thiodiglycol. Free thiodiglycol, free plus esterified thiodiglycol, and thiodiglycol sulfoxide excreted over 8 days accounted for less than 0.3%, 1-1.5%, and 3.4-4.3%, respectively, of the applied dose of sulfur mustard. In a further study, a modified analytical method was applied to determine these hydrolysis products and their acid-labile esters as the single analyte thiodiglycol, after treatment with acidic titanium trichloride. The excretion profile of the combined hydrolysis products was compared with the excretion profile of a different group of metabolites of sulfur mustard derived from the glutathione/beta-lyase pathway. These were also reduced to a common analyte, 1,1'-sulfonylbis-[2 (methylthio)ethane], after similar treatment with titanium trichloride. Urinary excretion of hydrolysis products determined in 4 rats over 8 days accounted for 3.7-13.6% of an applied cutaneous dose of sulfur mustard. Urinary excretion of beta-lyase metabolites accounted for 2.5-5.3% of the applied dose in the same group of rats. The excretion of beta-lyase products showed a much sharper decline than was observed for the hydrolysis products of sulfur mustard. PMID- 1501469 TI - Measurement of ethylenethiourea using thermospray liquid chromatography-mass spectrometry. AB - Reliable measurement of ethylenethiourea (ETU) is important because ETU is a potent thyroid carcinogen. A method for the separation and identification of ethylenethiourea (ETU) by applying reversed-phase high-pressure liquid chromatography (HPLC) followed by thermospray (TSP) mass spectrometry (MS) detection is described. Single ion recording detection applying HPLC-MS of ETU appeared to be highly selective and equally sensitive as an HPLC method applying UV detection reported in our earlier study (1). The detection limit for ETU was 100 pg per injection. PMID- 1501470 TI - Measurement of carbamazepine and its main biotransformation products in plasma by HPLC. AB - We present a method that permits the simultaneous analysis of carbamazepine (CBZ) and its major biotransformation products, carbamazepine-10,11-epoxide (CBZ-E) and carbamazepine-10,11-dihydroxide (CBZ-diOH), in plasma samples. The method consists of plasma extraction in alkaline medium with NaCl added using chloroform ethyl acetate (1:1, v/v) and later purification with n-hexane. The samples were submitted to reversed-phase chromatography (RP-18) using acetonitrile-water (3:7, v/v) as the mobile phase and detection at 220 nm. Recoveries of 62.0, 99.9, and 105.4% were obtained for CBZ-diOH, CBZ-E, and CBZ, respectively, with sensitivities of 0.32 micrograms/mL for CBZ-E and CBZ-dOH and of 0.64 micrograms/mL for CBZ. The method proved to be specific, thus permitting measurements in situations of drug combinations. PMID- 1501471 TI - Determination of procaine in equine plasma and urine by high-performance liquid chromatography. AB - The variability in plasma and urine equine procaine measurement between three independent laboratories using current methods led to the development of a sensitive, reliable, and reproducible high-performance liquid chromatographic method. Standardbred mares were administered either a penicillin G procaine preparation intramuscularly or procaine hydrochloride subcutaneously, and blood and urine were collected at defined time intervals. By HPLC the detection limits for procaine in plasma and urine were 1 and 10 ng/mL, respectively. In contrast procaine in plasma could not be detected by GC-NPD, while the urinary detection limit was 50 ng/mL. The concentration of fluoride in the collection tubes and repetitive freeze-thawing modified plasma procaine measurement. Urinary pH was a factor in estimation of urine procaine levels with greater recovery and reproducibility of results at pH 5 as compared to pH 7. This HPLC method provides a simple, sensitive, and reliable quantitation of procaine in equine plasma and urine. PMID- 1501473 TI - Evaluation of six commercial amphetamine and methamphetamine immunoassays for cross-reactivity to phenylpropanolamine and ephedrine in urine. AB - We evaluated six commercially available amphetamine (A) and methamphetamine (MA) immunoassays for their relative cross-reactivities to isomers of phenylpropanolamine (PPA) and ephedrine (E) in urine: Syva EMIT, Abbott fluorescence polarization (FPIA), Roche, and Diagnostic Products Corporation (DPC) radioimmunoassays for A and MA. Two stereoisomers of PPA and four stereoisomers of E were tested using (1) drug-free urine spiked at 1,000 mg/L or 100 mg/L of each compound and (2) 60 clinical urine specimens not containing A or MA but having varying amounts of PPA and/or E. Specimens responding greater than the 1-mg/L A or MA cutoff were defined as positive. All specimens spiked at 100 mg/L were negative by all immunoassays. All specimens spiked at 1,000 mg/L were positive by EMIT and negative by FPIA, Roche A, and DPC A; 1,000 mg/L/-E and d pseudoephedrine were also positive by Roche MA and DPC MA. Three of the 60 clinical specimens tested positive by EMIT and one specimen tested positive by DPC A and DPC MA. PMID- 1501472 TI - Continuous flow quantification of total mercury in whole blood, plasma, erythrocytes, and urine by inductively coupled plasma atomic emission spectroscopy. AB - Mercury determination in blood and urine can be performed by inductively coupled plasma atomic emission spectroscopy (ICPAES) after dilution in an ammonia buffer and reduction by sodium borohydride. The proposed method does not need an oxidative mineralization. The sample is not nebulized into the torch, but the mercury vapor, after collection in a reactor vial, is swept into the plasma by the argon carrier gas using the described glass apparatus. PMID- 1501474 TI - A rapid, simultaneous determination of paraquat and diquat in serum and urine using second-derivative spectroscopy. AB - A rapid, simple method based on second-derivative spectroscopy of the simultaneous analysis of paraquat and diquat in serum and urine is described. Paraquat and diquat in serum were deproteinized with sulfosalicylic acid, and those in urine were reduced with NaOH-dithionite solution. A qualitative and quantitative analysis of reduced paraquat and diquat was made at the amplitude peaks of 396-403 nm and 454-464 nm in the second-derivative spectra, respectively. The entire procedure was completed within about 10 minutes for a serum sample and within about 5 minutes for a urine sample. Application of the proposed method on a poisoned patient is also reported. PMID- 1501475 TI - Mass spectral characterization of three anthracycline antibiotics: a comparison of thermospray mass spectrometry to particle beam mass spectrometry. AB - Mass spectral results for three anthracyclines, doxorubicin, daunorubicin, and carminomycin are compared by using thermospray (TS) or particle beam (PB) [electron ionization (EI) and chemical ionization (CI)] instruments. Typically, positive ion TS mass spectrometry (MS) provided intense [MH]+ ions and some fragment ions, while PBMS in the EI mode provided only fragment ions. Significant [MH]+ ions were observed for carminomycin and daunorubicin when analyzed using PBMS in the positive ion CI mode. Under negative ion detection, TSMS yielded intense [M-H]- ions for these compounds while PBCIMS resulted in significant M- ions. Fragment ions observed in all three anthracyclines under positive and negative ion detection by TSMS and PBCIMS are due mainly to the cleavage of glycosidic bond, loss of H2O, and the loss of the side chain (COCH2R2) from the aglycone. PMID- 1501476 TI - Determination of nonderivatized para-hydroxylated metabolites of diazepam in biological fluids with a GC Megabore column system. AB - A method was developed using gas chromatography (GC) and a Megabore column system capable of simultaneous detection of diazepam, N-desmethyldiazepam, temazepam, oxazepam, and their para-hydroxylated metabolites. This method does not require derivatization of para-hydroxylated metabolites. Standard curves for pure reference compounds were linear, with the minimum detectable concentration of diazepam and its metabolites as low as 0.13 ng/injection. PMID- 1501477 TI - Simultaneous sequential determination of compounds of toxicological interest in mixtures by derivative spectroscopy. AB - An absorption spectroscopic method was developed for the sequential determination of mixture components. The proposed method is straightforward and convenient and provides optimal results that increase the potential of spectrophotometric techniques as applied to date. The method was applied to the sequential resolution of mixtures of pure components of toxicological interest yielding close UV absorption bands by using derivative spectroscopy. PMID- 1501478 TI - Hair analysis for drugs of abuse. III. Movement and stability of methoxyphenamine (as a model compound of methamphetamine) along hair shaft with hair growth. AB - This paper describes the movement of methoxyphenamine (MOP, a model compound of methamphetamine) along the hair shaft at the rate of hair growth and the stability of drugs in hair for several months. Five healthy subjects (3 males and 2 females) took 50 mg of methoxyphenamine orally once a day for 7 days. Scalp hairs from the posterior vertex were collected every 2 weeks or every 8 weeks after the first dosage. The hairs were cut into 1-cm sections and extracted with methanol-5N HCl (20:1). MOP in the extract was determined by gas chromatography/mass spectrometry (GC/MS) with tetradeuterium labeled MOP as an internal standard. The drug moved along hair shaft at the rate of 2.8-3.2 mm/week, according to hair growth, without diffusion. When drug bands were extrapolated according to the sections in which drug was detected, the bands were approximately 5 mm wide, equivalent to 1.7-2.4 periods of 7-day hair growth. In the case of identical doses, the drug level was highest in the root side and lowest in the distal side. In our data, we found that the drug level in hair had decreased approximately 50% five months later. The ratio of drug levels in corresponding sections correlated well to the ratio of doses, except where the hair shafts had been damaged or the drugs had decomposed. PMID- 1501479 TI - Determination of serum levels of dietary thiocyanate. AB - A spectrophotometric method was used to determine thiocyanate (SCN-) levels in human serum, in an attempt to relate serum levels of this ion to the dietary intake of vegetables of the genus Brassica. Thiocyanate ion was measured before and after a one-week period during which the subjects ate a diet rich in these vegetables. We also determined the serum increase in SCN- 2 h after the administration of 0.5 g KSCN. PMID- 1501480 TI - The analysis of cocaine and benzoylecgonine in meconium. AB - We describe an assay for measuring cocaine and benzoylecgonine in meconium of infants born to mothers suspected of using cocaine during their pregnancy. The assay involves the use of fluorescence polarization immunoassay (FPIA) to screen for benzoylecgonine in a methanolic extract of the meconium. The FPIA is sensitive to 0.6 microgram benzoylecgonine per gram meconium. Confirmation of the presence (or absence) of benzoylecgonine and cocaine in meconium samples was performed by solid phase extraction of a second methanolic extract of the meconium, derivatizing using BSTFA, followed by a gas chromatographic/mass spectrometric (GC/MS) analysis, which can detect both cocaine and benzoylecgonine. The GC/MS confirmation was sensitive to less than 0.25 microgram cocaine or 0.5 microgram benzoylecgonine per gram meconium. FPIA, which is commonly used in many toxicology laboratories, is advantageous because it precludes the need to use radioimmunoassays for the initial screen. The confirmation step provides greater certainty for the presence of cocaine and/or benzoylecgonine in meconium. PMID- 1501481 TI - Solid-phase extraction of drugs from biological tissues--a review. AB - Solid-phase extraction procedures are being used increasingly in all types of drug testing laboratories, including those which carry out forensic toxicology. The advantages of such procedures include decreased operator time, reduced solvent volumes, and increased extraction efficiency. The application of existing techniques, however, has not yet been applied to tissues that are widely available postmortem. Tissue analysis can make the task of interpretation of drug levels much easier, particularly where unstable drugs are involved (e.g., cocaine). This review article explores the possibilities of applying existing extraction procedures to human tissue samples. We also consider the reasons why forensic laboratories have been slow to investigate such possibilities. We hope to stimulate interest in alternative tissue extraction procedures by reviewing reported procedures that apply to both human and animal tissue. PMID- 1501482 TI - Medicolegal alcohol determination: implications and consequences of irregularities in blood alcohol concentration vs. time curves. PMID- 1501483 TI - The relationship between duplicate reproducibility and concentration in breath alcohol testing programs. PMID- 1501484 TI - Divergent perceptions of lesbians: a comparison of lesbian self-perceptions and heterosexual perceptions. AB - Social-psychological research on stereotyping was applied to lesbianism among American college students. The hypothesis that stereotypes of lesbians are often inaccurate predictors of individual lesbians was supported. Using stereotypes of lesbians identified by previous research, lesbians rated themselves on a series of bipolar stereotypical adjectives, and a comparison group of nonlesbians rated lesbians as a group on these same adjectives. Significant differences were found on 16 of the 21 adjectives. Knowing a lesbian personally did not influence heterosexuals' ratings, suggesting the resistance of stereotypes to change. PMID- 1501485 TI - Fraisse's theory of emotion and aggression. AB - This article shows how Fraisse's (1964) theory of emotion is a better explanation of aggression than any other theory of emotion. It discusses conceptual and methodological difficulties in existing theories of aggression and reports a study that supports a hypothesis based on Fraisse's theory. This study, which used Canadian university students equally divided by sex, supports the hypothesis that subjects would be more aggressive when faced with an unexpected annoyance than with an expected annoyance. Aggression was indexed by subjects' evaluation of the target person (confederate) as a source of annoyance. PMID- 1501486 TI - Predicting Zimbabwean women's ability to tell their partners to use condoms. PMID- 1501487 TI - Social support as a moderator of the effect of work stress on personal strain among black employees in South Africa. PMID- 1501488 TI - Psychoticism, extraversion, and neuroticism among Batswana adolescents. PMID- 1501489 TI - War and hunting poisons of the New World. Part 1. Notes on the early history of curare. AB - The history to about 1850 of the muscle-relaxant poison curare is discussed, especially the developments leading to the botanical identification of the plants that yield the alkaloidal active principles: Loganiaceae (Strychnos species) and Menispermaceae (Abuta, Chondrodendron, and Curarea species). One of the earliest encounters with the poison appears to have been during the exploration of the Lake Maracaibo region in Colombia by Alonso Perez de Tolosa in 1548. It is pointed out (yet again) that Sir Walter Ralegh did not bring back the poison to Europe in 1595 and that it was Keymis who first came across the word ourari when exploring the lower reaches of the Orinoco in 1596. Gumilla, La Condamine, Ulloa, Veigl, and others gave much additional information about the poison during the 18th century. Scientific studies began in the latter part of the century when Schreber listed the botanical identities of four of the plant components entering into the curare prepared by the Akawai Indians of Surinam. As far as is known, none of these people actually saw curare being made. Thereafter, progress was rapid. Humboldt and Bonpland were the first trained scientists to witness the preparation of the poison, at the very beginning of the 19th century. Subsequent exploration by Martius and Spix, Poeppig, Youd, the Schomburgk brothers, De Castelnau and Deville, Spruce, and others, up to the middle of the century, extended and deepened botanical and ethnological knowledge of curare. Study of its physiology started at about that time with the classical experiments of Rudolf von Koelliker and Claude Bernard. PMID- 1501490 TI - Recent advances on ginseng research in China. AB - Ginseng, Panax ginseng C.A. Meyer, is a well-known Chinese traditional medicine. There have been more than 300 original papers in Chinese and in English during the last 10 years in China. This review paper summarizes some achievements from some of these published papers. Twenty-eight ginsenosides and some minor constituents were extracted and isolated from the root, root-stock, stems, leaves, flowers and flower-buds of ginseng. The chemical analysis demonstrated that the content of ginsenosides is related to the source, part and growth years of ginseng. The drug has a wide range of pharmacological and therapeutical actions, it acts on the central nervous system, cardiovascular system and endocrine secretion, promotes immune function and metabolism, possesses biomodulation action, anti-stress and anti-ageing activities, and so on. Many preparations of ginseng have been officially approved for clinical application in China. Clinical evaluation has shown that these preparations play a special role in medicinal use. PMID- 1501491 TI - Antimicrobial activity of benzylisoquinoline alkaloids from Annona salzmanii D.C. AB - Bark of Annona salzmanii D.C. (Annonaceae), used in Brazilian folk medicine, was found to contain four benzylisoquinoline alkaloids, namely reticuline, anonaine, laurelliptine and isoboldine. Only anonaine possesses some antibacterial property while all four alkaloids show some antifungal activity. PMID- 1501492 TI - Uses, chemistry and pharmacology of Malouetia (Apocynaceae, subf. Apocynoideae). AB - An outline of the uses, chemistry, and pharmacology of the South American and African genus Malouetia A.DC. (Apocynaceae-Apocynoideae) is given. The chemotaxonomy of the genus is also discussed. PMID- 1501493 TI - Comparative study of the effects of beta-sitosterol, estradiol and progesterone on selected biochemical parameters of the uterus of ovariectomised rats. AB - A comparative study was made of the effects of beta-sitosterol, estradiol-17 beta and progesterone, individually and in combinations, on certain biochemical parameters important to carbohydrate metabolism in the uteri of adult ovariectomised rats. beta-Sitosterol (SITO), estradiol (E2) and combined treatment (SITO + E2) induced significant increases in glycogen concentration and the activities of glucose-6-phosphate dehydrogenase (G6PDH), phosphohexose isomerase (PHI) and total lactate dehydrogenase (LDH). Progesterone (P) administration however, raised only the uterine PHI and LDH activities. Co administration of P with beta-sitosterol (P + SITO) suppressed the SITO-induced increase in glycogen concentration and G6PDH activity. On the other hand, combined treatment (P + SITO) augmented total LDH activity. PMID- 1501494 TI - Analysis of some Malaysian dart poisons. AB - An investigation of nine Malaysian dart poisons has confirmed that their main active components are cardenolides from Antiaris toxicaria (Pers.) Lesch. and alkaloids probably from different forms of Strychnos ignatii P. Bergius. It is not possible to determine the ethnic origin of the poisons from the results of the analyses on their own. Two new cardiac glycosides have been isolated and their structures determined as 12 beta-hydroxycannogenin 3 beta-O-beta-D deoxygulopyranoside and 3 beta-O-alpha-L-rhamnopyranoside, respectively. PMID- 1501495 TI - Indigenous phytotherapy of gastrointestinal disorders in a lowland Mixe community (Oaxaca, Mexico): ethnopharmacologic evaluation. AB - Gastrointestinal disorders are one of the major health problems in developing countries. Sixty-five plants used popularly in the treatment of such disorders in a Mixe Indian community in Oaxaca (Mexico) and collected during a fieldstudy of 15 months are described. According to indigenous criteria a plant is used in the treatment of a certain illness because of the plant's characteristic smell and taste. Plants with astringent properties are particularly valued to treat diarrhoea and dysentery. Bitter, aromatic and bitter-aromatic plants are especially employed to treat gastrointestinal cramps and pain. Additionally, the efficacy of these plants was evaluated using ethnobotanical, phytochemical and pharmacologic information on the plants. The majority of the plants contain chemicals that may produce the effects desired by the Mixe. Frequently tannin containing drugs are used to treat diarrhoea and dysentery. A large number of the plants used by the Mixe in the treatment of gastrointestinal pain contain essential oil or bitter principles. As a result of this evaluation, plants were selected which should be studied phytochemically and pharmacologically with priority, to evaluate further their potential in the treatment of gastrointestinal disorders. PMID- 1501496 TI - Parasitological and microbiological evaluation of Mixe Indian medicinal plants (Mexico). AB - Medicinal plants are an important health resource in many regions of the Americas and are of particular importance to many Indian communities. Based on a recent ethnobotanical study in Mexico, we investigated the activity of 29 plant extracts against Entamoeba histolytica, three bacteria (Bacillus subtilis, Escherichia coli, and Micrococcus luteus) and two fungi (Cladosporium cucumerinum and Penicillium oxalicum). After separation of these extracts between CH2Cl2 and H2O the resulting phases were also evaluated. PMID- 1501497 TI - The medicinal flora of Majouri-Kirchi forests (Jammu and Kashmir State), India. PMID- 1501498 TI - Daime--a ritual herbal potion. PMID- 1501499 TI - Adverse effects of traditional drug preparations. PMID- 1501500 TI - In vivo selective monitoring of basal levels of cerebral dopamine using voltammetry with Nafion modified (NA-CRO) carbon fibre micro-electrodes. AB - The electrochemical technique of differential pulse voltammetry (DPV) with micro biosensors has been used for a number of years to monitor in vivo and in situ changes in the extracellular concentration of cerebral ascorbic acid, as well as that of the metabolites of dopamine (DA) and serotonin (5-HT). We have recently prepared a carbon fibre micro-electrode (mCFE) which specifically pretreated and coated with Nafion (a negatively charged polymer which repels acids such as 3,4 dihydroxyphenylacetic acid (DOPAC)) allows the direct selective detection of the oxidation of DA and 5-HT in nanomolar concentration in vitro and that of extracellular basal levels of cerebral 5-HT in vivo (peak B at +240 mV). We describe here a modified version of this micro-biosensor now called NA-CRO mCFE as its active tip (30 microns in diameter) is coated with a 50/50 (v:v) mixture of Nafion and dibenzo-18-crown-6 (Aldrich). In vitro this newly reported electrode shows insensitivity to acids (e.g., DOPAC) up to 100 microns and sensitivity to 0.5-1 nM DA. In vivo, in the striatum of anaesthetised rats, a basal oxidation peak at +80 mV (peak A, on average 0.6 nA in height), which corresponds to the oxidation potential of DA in vitro, is consistently detectable with the NA-CRO mCFE (corresponding to an estimated concentration of 1.5 nM). Experiments performed in vivo in anaesthetised rats implanted in the striatum with uncoated (normal) mCFE to measure extracellular DOPAC or with NA-CRO mCFE have been performed in order to analyse the chemical nature of peak A in vivo. It is concluded that the addition of the crown-ether compound to the Nafion coat improves the sensitivity of the micro-biosensor for DA in vitro and allows the detection of its basal extracellular levels in vivo. PMID- 1501501 TI - A method for automatic identification of periods of muscular activity from EMG recordings. AB - A computer-based method of identifying periods of activity in EMG recordings is described. Its application to the analysis of muscle activity patterns in freely moving human or animal subjects is illustrated and discussed. PMID- 1501502 TI - Clinical experience with reinforced, anchored intramuscular electrodes for functional neuromuscular stimulation. AB - Implanted intramuscular electrodes must remain functional for many years if functional neuromuscular stimulation (FNS) is to become a standard treatment in paralysed individuals. In initial trials we found that 5 of 11 coiled single-wire FNS electrodes implanted in 3 patients failed within 8 months. Consequently, we turned to a reinforced electrode comprising 2 multi-stranded, insulated wires tandem-wound on a prolene core and terminated by a prolene anchor or tine (after Mortimer et al., 1986, 1987). The electrodes were implanted with a translumbar aortogram needle, the teflon sheath of which enabled us to stimulate through the tip to guide placement. We have monitored the electrical and functional properties of 8 reinforced electrodes implanted in 2 incomplete quadriplegic patients over 22 months. Four of the electrodes were used for at least 1 h daily to exercise muscles or to provide FNS in gait. Electrical impedances, thresholds and elicited limb motion remained constant in all 8 electrodes over the test period. Disadvantages of the reinforced electrodes are (1) difficulty of eventual removal, and (2) risk of pathogenic infiltration is increased by the 3-filament structure (fortunately dense tissue encapsulation seems to mitigate infection). We conclude that tandem-wound, prolene-reinforced FNS electrodes are much more robust than previous single-coil designs and may form the basis for FNS devices of the future. PMID- 1501503 TI - Simultaneous recording of [Ca2+]i increases in isolated olfactory receptor neurons retaining their original spatial relationship in intact tissue. AB - A new method is described for isolating olfactory receptor neurons suitable for simultaneous recording of odorant responses in several cells. This method, called "tissue printing" by Cassab and Varner, was used to isolate cells for measurement of odorant-induced increases in cytosolic-free calcium concentration ([Ca2+]i) using the Ca2+ indicator dye fura-2. A large number of receptors could be isolated from a piece of olfactory epithelium (about 300 microns square), preserving their normal morphology and relative local topology to that in the intact olfactory tissue. The probability that there are one or more receptor cells with odorant-induced responses in [Ca2+]i per preparation was 4 times higher with cells isolated by the tissue printing than with those obtained by the pipetting method. The responses of 2 receptor cells separated by 28 microns in the recording chamber differed for 2 odorants: isoamyl acetate and citralva. The method was useful for isolating receptor neurons without losing their morphological features and for investigating the spatial distribution of odorant responsiveness of each receptor over the olfactory epithelium. PMID- 1501504 TI - Deblurring of 3-dimensional patterns of evoked rat cerebellar cortical activity: a study using voltage-sensitive dyes and optical sectioning. AB - One of the benefits of imaging neuronal activity is the capability of resolving spatial patterns in the x-y plane. With optical sectioning microscopy, the 3 dimensional (3-D) structure may also be studied without physical deformation by serially moving the focal plane of the microscope through the volume of interest along the focal axis. However, each image is blurred by contributions from neighboring planes. This degradation is most severe for low numerical aperture lenses and large amounts of defocus. In this study, an image restoration method using the optical properties of an aberration-free, defocused optical system has been developed for improving optical signals from voltage-sensitive dyes. Deblurring based on the optical transfer function (OTF) of the system was applied on two test sets of serially sectioned images: (1) fluorescent beads and (2) in vivo rat cerebellar cortex stained with the voltage-sensitive dye RH795. This method was shown to reduce significantly the out-of-focus contribution to the images, improving the spatial resolution not only in the x-y plane, but also the z axis. The algorithms were then applied to optical signals obtained by stimulation of the cerebellar surface. Optical signals having a distinct beam like pattern were evoked and recorded over depths ranging from 0 to 300 microns prior to deblurring. Application of the deblurring algorithm reduced the depth of cerebellar cortex over which the optical signals were observed. In agreement, field potential recordings of the evoked parallel fiber volley and post-synaptic components were restricted to a narrow range of depths similar to the deblurred optical images. Removal of out-of-focus information is an essential step in the serial sectioning of central nervous system structures for neuronal imaging and 3 D reconstruction. PMID- 1501505 TI - Ethidium bromide fluorescence of 28S ribosomal RNA can be used to normalize samples in northern or dot blots when analyzing small drug-induced changes in specific mRNA. AB - Quantitative analysis of Northern blots is frequently accomplished with the aid of an internal standard. Most common is probing for an additional message the steady-state levels of which do not change in response to the experimental conditions and the signal of which is sufficiently removed from that of the target gene after gel electrophoresis. However, this strategy is not always feasible. When total RNA is immobilized on nylon, 28S ribosomal RNA on the blot can be used as an internal standard and quantitated by scanning the negative photograph of the blotted RNA stained with ethidium bromide. This procedure can also be used for RNA dot blots. The method is quick, reliable, will work with laser or white-light densitometers, and can serve as a universal internal standard, eliminating the need for additional probes. PMID- 1501506 TI - Parametric analysis of sojourn times in conditioned place preference experiments. AB - In conditioned place preference experiments, groups of animals are typically compared by means of the total time spent in a treatment environment. The total times are often positively skewed, which prohibits the use of parametric procedures that require normal distributions. Common response time models for such total times are also inadequate because the fit of the models to the data is often poor. The present paper assumes that the sojourn times of a single animal are independent and that they all follow the same 1-parameter exponential model. The exponential parameter allows a number of simple interpretations. We propose point estimates, confidence intervals, a goodness-of-fit test, and a test for comparing 2 samples. The procedures are also applied to single animals, and a test is given for comparing the animals of a group. The kind of parametric analysis suggested enables better interpretation than does the simple distribution-free comparison of 2 groups based on the total time spent in the treatment environment. PMID- 1501507 TI - Analysis of the structure of the muscular pulmonary arteries in patients with pulmonary hypertension and COPD: National Institutes of Health nocturnal oxygen therapy trial. AB - We examined the cardiovascular function as well as the structure of the muscular pulmonary arteries in patients who had died while enrolled in the National Institutes of Health nocturnal oxygen therapy trial (NOTT). The cardiovascular function of the patients classified into groups based on the severity of the pulmonary hypertension was examined, and we compared the morphologic data in these groups to those obtained from age-matched controls who died with no evidence of cardiovascular disease. The groups with severe pulmonary hypertension had markedly increased pulmonary vascular resistance but similar cardiac index to the group with only mild hypertension. In the structural analyses, we found definite alterations in arterial structure from the control population: the patients who had pulmonary hypertension had markedly increased percentages of intima and media. These differences were most pronounced in the medium and larger muscular arteries. The degree of pulmonary hypertension did not appear to alter vascular structure consistently, although there was a trend towards an increase in muscle media in the smaller vessels. When the patients were classified into a group who responded to oxygen administration by a decrease in Ppa, and an age- and Ppa-matched group who did not respond, there were no differences in vascular structure between these groups, although both groups had greater percentages of intima and media compared to the control group. We conclude that, in patients with pulmonary hypertension secondary to chronic obstructive pulmonary disease (COPD), there are structural alterations of the muscular pulmonary arteries, but these do not correlate with either the severity of the pulmonary hypertension or the ability of the pulmonary vasculature to respond to oxygen administration. PMID- 1501508 TI - The search for tumor-associated proteins in pleural effusions by means of monoclonal antibodies and a dot blot assay. AB - Liquid moiety of 61 pleural effusions was tested for tumor-associated proteins (TAP) by means of a dot immunobinding (dot blot) assay (DIA) and a panel of monoclonal antibodies (Moabs). The sensitivity of the assay was checked using a purified, serially diluted carcinoembryonic antigen (CEA) preparation and an anti CEA monoclonal IgG system. The latter was examined using both DIA and enzyme linked immunosorbent assay ELISA solid phase assays in simulated conditions that mimicked the protein content of effusions. Finally, the results of DIA were compared to the immunohistochemistry carried out on cell sediments from the same effusions with similar Moabs. It was found that the prevalence of several TAPs, including CEA, epithelial membrane antigen (EMA), vimentin, tenascin, and Thomsen Friedenreich antigen, was significantly higher in the malignant effusions than in the nonmalignant ones. A total, larger than 2, of detected TAPs in a given fluid, was found almost exclusively in malignant effusions (p less than 0.0001). The detection limit of the DIA for a CEA was determined at 5 ng/ml, while for the ELISA it was 1 ng/ml. Several TAPs, especially the CEA, could be detected in parallel tests, carried out on the liquid moiety and the cell sediments of malignant effusions. The evaluation of selected TAPs in pleural effusions by dot blot assay may be of clinical value. PMID- 1501509 TI - Influence of exercise-induced bronchoconstriction on refractoriness. AB - This study determined if the degree of exercise-induced refractoriness is determined by the degree of exercise-induced bronchoconstriction. In 12 patients with exercise-induced asthma (mean [SEM] age 27 [3] years) we performed 2 pairs of exercise challenges 45 min apart at different work loads on 2 days. Mean (SEM) total respiratory heat loss during low and high work loads was 3.4 (0.2) and 5.1 (0.4) kcal, respectively. After the first and second exercise challenge at low work loads, mean (SEM) SRaw increased by 107 (15) and 73 (16)% (n.s.), as compared to 361 (40) and 98 (25)% at high work loads (p less than 0.005). We found a correlation between the initial airways response and refractoriness (r = 0.58, p less than 0.005) and conclude that the degree of refractoriness after exercise-induced bronchoconstriction is in part dependent on the severity of exercise-induced bronchoconstriction. PMID- 1501510 TI - Advances in sodium-ion coupled biogenic amine transporters. AB - The sodium-ion coupled transporters for 5-hydroxytryptamine (5HT), noradrenaline and dopamine function to reduce extracellular levels of biogenic amines. Over the past fifteen years selective inhibitors of these transport systems have been developed including fluoxetine, citalopram, paroxetine, litoxetine (for 5HT), nisoxetine, desipramine, maprotiline (for noradrenaline) and GBR-12935 (for dopamine). Some of these inhibitors, including drugs selective for noradrenaline transport and particularly those selective for the 5HT transport system are currently widely used in the clinical management of affective disorders. Selective biogenic amine uptake inhibitors have, in addition, provided tools to undertake molecular pharmacological and biochemical studies of their respective transporters. By this means, the rat brain 5HT and dopamine transporters have been identified as polypeptides with relative molecular masses of 73,000 and 80,000, respectively, using affinity-chromatographic purification and photoaffinity-labelling techniques. Recently, the biogenic amine transporters have been cloned and a comparison of their predicted amino acid sequences reveals that these proteins share a considerable degree of similarity with notably 12-13 transmembrane spanning domains. Perspectives for future fundamental and clinical research on biogenic amine transport systems using molecular biological techniques are discussed. PMID- 1501511 TI - Pharmacokinetic simulations of SPECT quantitation of the M2 muscarinic neuroreceptor subtype in disease states using radioiodinated (R,R)-4IQNB. AB - Alzheimer's disease (AD) involves selective loss of muscarinic M2, but not M1, subtype neuroreceptors in the posterior parietal cortex of the human brain. Emission tomographic study of the loss of M2 receptors in AD is limited by the fact that there is currently no available M2-selective radioligand which can penetrate the blood-brain barrier. However, by taking advantage of the different pharmacokinetic properties of (R,R)-[123I]IQNB for the M1 and M2 subtypes, it may be possible to estimate losses in M2. It has previously been hypothesized that the difference between an early study and a late study should provide information on the M2 receptor population. In order to test this hypothesis, we present here the results of pharmacokinetic simulations of the in vivo localization of (R,R) [123I]IQNB in brain regions containing various proportions of M1 and M2 subtypes. These results permit us to conclude that SPECT imaging of (R,R)-[123I]IQNB localization can potentially be used to quantitate changes in the M2 subtype in a disease state within a brain region for which the ratio M2/M1 is sufficiently high in normal individuals. PMID- 1501512 TI - Synthesis and bioactivity studies of two isosteric acyclic analogues of melanin concentrating hormone. AB - Salmon melanin concentrating hormone (MCH) is a cyclic heptadecapeptide. MCH stimulates perinuclear aggregation of melanosomes within integumental melanocytes of teleost fishes resulting in skin blanching. MCH contains a disulfide bridge forming a 10-residue ring [sequence: see text]. It has been proposed that the ring is necessary for maintenance of potency. In order to test this proposal, we have synthesized two pseudo-isosteric analogues of MCH that cannot cyclize. They differed only in the polarity of the side chain group of positions 5 and 14. Serine was substituted for Cys5 and Cys14 in one peptide and L alpha aminobutyrate (Abu) was the substitution at the two positions in the other peptide. Using a fish skin bioassay we determined that these analogues exhibit less than 1/10,000th the potency of the native hormone. These results suggest that the disulfide bridge is necessary to maintain the correct conformational and topographical features of the hormone for receptor binding and transmembrane signal transduction. PMID- 1501513 TI - Sodium-lithium countertransport and body fat distribution. AB - The relationship between erythrocyte sodium-lithium countertransport (Na-Li CT) and body fat distribution is analyzed in a sample (n = 101) of normotensive and untreated hypertensive men participating in an epidemiological study of coronary heart disease risk factors. Na-Li CT is significantly and positively associated with both subscapular skinfold and waist to hip ratio, but not with triceps skinfold. The univariate correlation between Na-Li CT and blood pressure is diminished when adjusted for body mass index and waist to hip ratio. These findings support the existence of an association between Na-Li CT and central body fat distribution and suggest that the metabolic abnormalities associated with centrally distributed body fat could explain, at least in part, the association between Na-Li CT and blood pressure. The maximal velocity of the sodium-lithium countertransport (Na-Li CT) in erythrocytes has been reported to be directly associated with blood pressure and hypertension in numerous reports from both clinical and epidemiological studies. In most of these studies, indices of weight and/or adiposity (body mass index, in particular) have been shown to be among the most important correlates of Na-Li CT. Adiposity is an important determinant of blood pressure, and there is evidence suggesting that the patterning of the fat cells in the body is linked to a number of metabolic disturbances that could lead to hypertension and an increase in other CHD risk factors. The present report analyses the relationship between Na-Li CT and body fat distribution in a sample of normotensive and untreated hypertensive men participating in an epidemiological study. PMID- 1501514 TI - Response to 5-hydroxytryptamine on neurons of guinea pig celiac and inferior mesenteric ganglia in primary culture. AB - The electrophysiological effects of serotonin, a putative neurotransmitter in prevertebral sympathetic ganglia, were evaluated in cultured celiac and inferior mesenteric ganglia (IMG) neurons. Intracellular microelectrode recordings were performed in neurons that were maintained in culture an average of 26 days. Seventy-eight of 85 neurons responded when serotonin (10 microM) was applied by pressure ejection from a micropipette to the surface of the isolated cells. The majority of the neurons (n = 48) generated fast depolarizations, although slow depolarizations (n = 17), bipolar responses (n = 5), hyperpolarizations (n = 7), and a biphasic response (n = 1), were also seen. Hyperpolarizing responses were evoked in celiac neurons only. All responses were inhibited by the 5-HT3 antagonist MDL 72,222 (5 microM). Fast responses were not inhibited by tetrodotoxin (n = 3). These results demonstrate that serotonin evokes a variety of membrane potential changes in cultured prevertebral sympathetic neurons by activating 5-HT3 receptors. PMID- 1501515 TI - Free fatty acids have nucleating effects in model biles. AB - Nucleating factors are thought to be responsible for the more rapid nucleation of gallbladder bile from patients with gallstones as compared to controls. Biliary proteins and, in particular, mucus and non-mucus glycoproteins are the focus of current research. Non-protein nucleating factors were not extensively investigated. In this study we studied the role of free fatty acids (FFA) as possible nucleating factors. Palmitic, oleic and linoleic acid were added to model biles in increasing concentrations from 0 to 20 mu mol/ml. The nucleation time of model biles decreased to 45%-60% of the initial following the addition of 0.5 to 1 mu mol/ml of each of the three fatty acids. Only a small further decrease in the nucleation time was noted with higher concentrations of up to 20 mu mol/ml. The pronucleating effect of FFA added to whole model bile was also examined in the isolated vesicular and non-vesicular fractions. The decrease in the nucleation time at each concentration of the three fatty acids was in the following order of magnitude: whole bile greater than vesicular phase greater than non-vesicular phase. The addition of each of the three fatty acids resulted in a partial solubilization of vesicles, with transfer of their lipid contents to the non-vesicular fraction. The effect was more marked with oleic acid and least marked with linoleic acid. The vesicular cholesterol to phospholipid ratio did not change following the addition of exogenous free fatty acids. Studies with labeled FFA showed that they migrated with the non-vesicular fraction on gel chromatography.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1501516 TI - Effect of thermal injury on transfer of IR22 IgA myeloma protein into bile in the rat. AB - We previously observed a 75-90% decrease in concentration of biliary IgA after thermal injury to rat skin. Decrease in biliary IgA might result from an alteration in supply of polymeric IgA delivered to the hepatocyte or from an alteration in hepatocyte transfer of polymeric IgA into bile. In the present study, we examined the transfer of intravenously administered 125I-IgA into bile. Purified IR22 rat IgA myeloma protein consisting of both monomeric and polymeric IgA was labelled with 125I. Sprague-Dawley rats (140-180 g) received a 20-30% body surface area scald-burn or sham treatment. The bile duct was cannulated 18 24 h later and 125I-IgA preparations were injected into the tail vein. Bile was collected under light ether anesthesia for 3 h. In rats injected with 125I-IR22 IgA myeloma protein there were no significant differences in total, TCA precipitable, or immunoprecipitable radioactivity in bile from burn-injured or sham-treated animals. On Bio-Gel A-1.5 m gel permeation, the radioactivity in bile from sham-treated animals eluted in the region of polymeric IgA as expected; the radioactivity in the bile from burn-injured animals eluted equally in the same regions as polymeric IgA and monomeric IgA. In sham-treated rats injected with isolated polymeric IgA only, bile contained primarily polymeric IgA. In burn injured rats injected with polymeric IgA only, bile contained a mixture of polymeric IgA and monomeric IgA. These findings suggest that hepatocyte processing of polymeric IgA is altered after thermal injury, resulting in the transformation of some polymeric IgA into its monomeric form. PMID- 1501517 TI - Bile duct hemorrhage: a biopsy finding after cholangiography or biliary tree manipulation. AB - We report on 13 patients with a distinctive bile duct lesion that presented histologically as erythrocyte engorgement of the epithelium of the small bile ducts, resulting in a red-beaded appearance. In ten of our cases, the lesion was associated with a recent history of cholangiography, and in two of our cases with vigorous manipulation of the distal biliary tree, raising the possibility that the hemorrhage might have been caused by increased pressure within the ducts during cholangiography or as a result of mechanical trauma to the biliary system. PMID- 1501518 TI - Variations in human liver fucosyltransferase activities in hepatobiliary diseases. AB - The hyperfucosylation of a number of glycoconjugates observed in liver diseases involves the action of several specific fucosyltransferases (F.T.) notably responsible for synthesizing histo-blood group antigens. We determined the activities of alpha 3, alpha 2 and alpha 3/4 F.T. in 35 liver biopsy samples from patients with fatty liver, alcoholic or post-hepatic liver cirrhosis, primary or secondary biliary cirrhosis, acute hepatitis or a normal liver. F.T. activities were measured by transfer of GDP [14C] fucose to asialotransferrin for alpha 3 F.T., to phenyl beta-D-galactoside for alpha 2 F.T. and to 2' fucosyllactose for alpha 3/4 F.T. The diseased liver extracts showed an early increase in non-Le gene-associated alpha 3 F.T. activity (p = 0.001), which was related to the number of steatosic hepatocytes and the degree of intralobular inflammatory infiltration. Overexpression of this alpha 3 F.T. provides an explanation for the strong expression of 3-fucosyl lactosamine structures described in several hepatobiliary diseases. alpha 2 F.T. levels were significantly elevated in the two groups of liver cirrhosis and acute hepatitis (p = 0.05), but not enough to consider alpha 2 F.T. as a sensitive feature of mesenchymal cell injury. All Lewis-positive biopsies displaying biliary alterations showed increased Le gene encoded alpha 3/4 F.T. activity (p = 0.001), which was related to the intensity of neoductular proliferation. Elevated levels of alpha 3/4 F.T. may be a very early sign of biliary regeneration. PMID- 1501519 TI - Estradiol-17 beta modifies the induction of spermidine/spermine N1 acetyltransferase activity in the liver of lipopolysaccharide-treated mice. AB - In an attempt to elucidate the effects of estrogen on polyamine metabolism in lipopolysaccharide (LPS)-treated mice, we assayed polyamine content and the activity of spermidine/spermine N1-acetyltransferase (SAT) and ornithine decarboxylase (ODC) in some organs. LPS elevated N1-acetylspermidine levels in the liver and lung and putrescine levels in the liver, lung and spleen. LPS increased the activity of ODC at 6 h and that of SAT at 12 h in the liver. When estradiol-17 beta was simultaneously administered with LPS, the maximum increase in hepatic N1-acetylspermidine levels was found 6 h earlier than in the LPS control. Likewise, the peak of the hepatic SAT activity after LPS-treatment was observed 6 h earlier in the estradiol-17 beta-treated mice than in the LPS control. No such effect of estradiol-17 beta was found in the lung and spleen. The LPS-induced ODC activity was not affected by estradiol-17 beta in the liver, lung or spleen. Estrone and 16 beta-ethylestradiol (an anti-estrogen) were also effective in enhancing the LPS-induced elevation of N1-acetyl-spermidine and putrescine in the liver, while both diethylstilbestrol, which has a potent estrogenic activity without steroid structure and estradiol-17 alpha (a non estrogenic isomer of estradiol-17 beta) were without effect. Tamoxifen (an estrogen receptor antagonist) did not suppress the estrogen-induced increase in hepatic N1-acetylspermidine levels. PMID- 1501520 TI - Factors influencing contrast in fast spin-echo MR imaging. AB - Multi-echo pulse sequences for producing T2-weighted images in much reduced imaging times have recently been developed for routine clinical use. A number of recent articles have described the contrast obtained with fast spin-echo (FSE) sequences and have generally indicated that they depict tissues very similarly to conventional spin-echo (SE) imaging. There are, however, some important differences in contrast between some tissues in FSE images. This work presents a detailed study of the contrast obtained with FSE imaging sequences and examines the image sequence and tissue parameters which influence contrast. The use of multiple refocusing pulses produces several subtle effects not seen in conventional SE imaging sequences, and in this study the precise nature and extent of such effects are described. The relative contributions to image contrast of magnetization transfer, the decoupling of J-modulation effects, the production of stimulated echoes and direct saturation effects, of diffusion and of the effects of the differential attenuation of different spatial frequencies, are each quantified. The mechanisms responsible for the brighter fat signal seen in FSE images, as well as the loss of signal from some other tissues, are explained. Computer simulations, phantom experiments, and clinical images are all used to support the conclusions. PMID- 1501521 TI - Pelvic phased array coil: image quality assessment for spin-echo MR imaging. AB - The NMR phased array coil (PA) provides improved signal-to-noise ratio (SNR) over that available with the body coil. We evaluated image quality obtained with a pelvic PA compared to that obtained with the body coil for spin-echo imaging. Thirty-three women undergoing clinical pelvic MRI were imaged with the body coil followed by imaging with the PA with the same field-of-view (FOV) in 11 patients, and with a small FOV in 23 patients. Image quality was assessed independently by two radiologists. In individual cases there was significant improvement in image quality with the PA, however the expected marked improvement in image quality was not consistently found. Two factors which may limit image quality are increased motion artifact and nonuniformity of signal with distance from the coils. Significant improvements in image quality may occur with improved techniques to decrease motion artifact. PMID- 1501522 TI - Magnetic resonance findings in sarcoidosis of the thorax. AB - Fifteen patients with sarcoidosis underwent thoracic MRI examinations. The T2 signal intensity of lymphadenopathy varied, with no characteristic pattern noted. Three of four patients with bright lymph nodes on T2 images had stage I sarcoidosis, but low intensity nodes were also seen in stage I patients. Coronal images were complementary to axial images and better depicted subcarinal adenopathy. MRI does not distinguish the lymphadenopathy of sarcoidosis from other entities, but is useful for defining the anatomic extent of disease and differentiating pulmonary artery enlargement from adenopathy. PMID- 1501523 TI - MR knee imaging: axial 3DFT GRASS pulse sequence versus spin-echo imaging for detecting meniscal tears. AB - The knees of 17 patients (34 menisci) referred for magnetic resonance (MR) imaging to evaluate knee pain were examined using thin axial three-dimensional Fourier transform (3DFT) gradient-refocused acquisition in a steady state (GRASS) images through the menisci, to determine if this method is sensitive and specific for detecting meniscal tears. Results were compared with spin-echo images with long TR and double-echo TE in both coronal and sagittal planes. Arthroscopy results, available in each case, were used as the "gold standard." Twelve meniscal tears were identified at arthroscopy. Axial 3DFT GRASS technique detected 10 of the 12 meniscal tears compared to 9 or 12 using spin-echo technique. With axial 3DFT GRASS technique one false-positive meniscal tear was reported, compared with two false-positive tears on spin-echo images. Axial 3DFT GRASS images were very useful in detecting peripheral tears, showing displaced meniscal fragments, and evaluating complex tears. In this small study, thin axial 3DFT GRASS images were comparable to spin-echo images for detecting meniscal tears, and were helpful in complicated cases in which they provided complementary information to that obtained from spin-echo images. PMID- 1501524 TI - Mass-like hepatic hypertrophy: MRI findings with histologic correlation. AB - Hepatic parenchyma may hypertrophy following asymmetrical injury. The histologic characteristics of hypertrophic hepatic parenchyma are more similar to normal hepatic parenchyma than is the more severely damaged liver. We present four cases where large hypertrophic masses resembled neoplasm on other imaging modalities or at surgery, but had MRI signal characteristics similar to those of normal liver. PMID- 1501525 TI - Magnetic resonance imaging in human lymphedema: comparison with lymphangioscintigraphy. AB - Magnetic resonance (MR) imaging and isotope lymphography (lymphangioscintigraphy, LAS) was done in 32 patients with peripheral lymphedema (19 primary and 13 secondary). MRI characteristically showed diffuse dermal and subcutaneous edema, a nonedematous, occasionally hypertrophied skeletal muscle compartment, variability in regional lymph node size and appearance depending on the underlying clinical disorder, serpiginous "channels" or "lakes" consistent with dermal collateral lymphangiectasis and sequestered lymph, and increased subcutaneous fat. In contrast, LAS showed dermal diffusion ("backflow"), cross over with retrograde tracer backflow (reflux), delayed tracer transport, and depending on the cause of lymphedema (i.e., primary or secondary), discrete or poorly defined lymph trunks (tracer "bands") and delayed or nonvisualization of regional lymph nodes. Although not a first-line clinical test, MR particularly in conjunction with LAS noninvasively provides accurate anatomical definition of the peripheral lymphatic system. In contradistinction to LAS, MR can visualize lymph trunks, nodes, and soft tissues proximal to sites of lymphatic obstruction. Together these imaging modalities may substitute for conventional oil contrast lymphography in the evaluation of the pathogenesis and evolution of most lymphologic disorders. PMID- 1501526 TI - Evaluation of the susceptibility effect on gradient echo phase images in vivo: a sequential study of intracerebral hematoma. AB - Susceptibility effect of intracerebral hematoma was estimated on the phase images of gradient echo (GrE). Thirty-five hematomas were studied 3 hr to 5 yr after the onset, a total of 72 times with use of phase and magnitude images of GrE, as well as T1-, T2-, and density-weighted spin-echo (SE) images at 1.5 T. On the basis of the theory of electromagnetism, phase shift to hematoma was calculated for simplified models with concentric distribution of paramagnetic susceptibility. All hematomas were well visualized by the phase images, the pattern of which changed sequentially. The distribution of paramagnetic susceptibility could be estimated by correlating the observed phase shifts with the calculated one. SE images were necessary to presume the type of magnetic substances. A probable hypothesis of the evolution of intracerebral hematoma is proposed. PMID- 1501527 TI - The accuracy of signal intensity measurements in magnetic resonance imaging as evaluated within the knee. AB - Quantitative signal intensity measurements are being utilized in both clinical and research magnetic resonance imaging protocols. This paper addresses three questions in quantitative MRI measurements as evaluated within the knee: 1) the accuracy of quantitative measurements; 2) improvement of accuracy by phantom normalization; and 3) the amount of signal change that is clinically significant. Seven normal subjects were imaged on three different days within a 1-wk period. Test-tube phantoms of manganous chloride (MnCl2) were imaged posterior to the knee and were used to normalize each image. The variation in signal intensity within the same subject averaged 20% for both the anterior cruciate ligament (ACL) and the posterior cruciate ligament (PCL). The phantom variation was approximately 18%. Signal intensity normalization by background subtraction, background division, phantom division, or a combination of subtraction and division did not significantly improve either the phantom variation or the ligament variation. Given that an individual ligament intensity will be measured with standard errors of +/- 20% of its value, we calculated the minimum increase in signal intensity to be considered abnormal relative to a normal ligament. A relative signal increase of 46% can be considered pathologic with 95% confidence. These findings emphasize that quantitative measurements must be carefully assessed when being applied in clinical settings. PMID- 1501528 TI - In vivo evaluation of the reproducibility of T1 and T2 measured in the brain of patients with multiple sclerosis. AB - The precision (reproducibility) of relaxation times derived from magnetic resonance images of patients with multiple sclerosis (MS) were investigated. Measurements of 10 MS patients were performed at 1.5 T on two occasions within 1 wk. T1 and T2 was measured using a partial saturation inversion recovery sequence (6 points) and a Carr-Purcell-Meiboom-Gill phase alternating-phase shift multiple spin-echo sequence with 32 echoes. Regions of interest (ROI) were placed both in apparently normal white matter and plaques. The precision (+/- 1.96 SD) and the confidence intervals for T1 and T2 for white matter and plaques were calculated. The precision of T1 for white matter and plaques was respectively +/- 94 msec and +/- 208 msec. The precision of T2 for white matter and plaques was respectively +/- 18 msec and +/- 26 msec. For all measurements the coefficient of variation was about 9%. Judging from our own study and others as well, a precision better than 10% for T1 and T2 would seem unrealistic at present. PMID- 1501529 TI - Semiautomated quality assurance for quantitative magnetic resonance imaging. AB - It is now well established that MRI can be used for quantitative (as opposed to simply qualitative) measurements, and good accuracy and precision have been obtained in phantom experiments. To make routine quantitative measurements as part of a clinical scanning protocol, however, quality assurance (QA) methods particularly suited to quantification must be developed. We describe a set of QA tests using clinical protocols on test phantoms, with which we have assessed quantitative performance of our Picker 0.5-T scanner (Picker International, Cleveland, OH) over 2 years. We also describe the automated data processing methods we have developed to deal with the large amounts of data generated by these tests. PMID- 1501530 TI - Analysis of machine-dependent and object-induced geometric distortion in 2DFT MR imaging. AB - Geometric distortion in MR imaging predominantly arises from the inhomogeneity of the static field and the nonlinearity of the gradients. It is the purpose of this paper to analyse the object and machine related contributions to geometric distortion in order to determine which corrections are necessary for attaining a specified precision. System related imperfections were measured by systematic variation of the strength, direction, and polarity of the read-out gradient in imaging experiments on a grid of cylindrical sample tubes. For the 1.5-T system used in this study, static field related errors up to 7 mm and gradient related errors up to 4 mm were observed (midcoronal plane, FOV 400-mm, G-read between 0.5 and 3.0 mT/m). Field related errors were shown to be inversely proportional to gradient strength, whereas gradient related errors turned out to be virtually independent of gradient strength. It therefore seems recommendable to always apply the strongest available selection and read-out gradients when geometric fidelity is given preference to signal-to-noise considerations. Correction of system related geometric distortions in MR images can readily be performed by table lookup. Object-induced distortions of the gradient fields were studied by experiments on a grid of sample tubes immersed into a cylindrical water bath of variable saline concentration. These experiments revealed a negligible influence of the object on the gradient error distribution, and lead to the conclusion that correction for the nonlinearity of the gradients only requires the application of system dependent correction factors. Object-related distortions of B0 were studied by conventional SE and fat-suppressed IR experiments on phantoms and human subjects. In these experiments the polarity of the read-out gradient was reversed. Subtraction images showed significant object-induced inhomogeneities of the static field at tissue-air interfaces and in the immediate vicinity of the object being imaged. A first attempt to correct for object related B0 inhomogeneities was made by contour analysis of the source images. At present this correction still has to be done manually. PMID- 1501531 TI - Correction of spatial distortion in magnetic resonance angiography for radiosurgical treatment planning of cerebral arteriovenous malformations. AB - A treatment planning system based on magnetic resonance (MR) angiographic imaging data for the radiosurgery of inoperable cerebral arteriovenous malformations is reported. MR angiography was performed using a three-dimensional (3D) velocity compensated fast imaging with steady-state precession (FISP) sequence. Depending on the individual MR system, inhomogeneities and nonlinearities induced by eddy currents during the pulse sequence can distort the images and produce spurious displacements of the stereotactic coordinates in both the x-y plane and the z axis. If necessary, these errors in position can be assessed by means of two phantoms placed within the stereotactic guidance system--a "2D-phantom" displaying "pincushion" distortion in the image, and a "3D-phantom" displaying displacement, warp, and tilt of the image plane itself. The pincushion distortion can be "corrected" (reducing displacements from 2-3 mm to 1 mm) by calculations based on modeling the distortion as a fourth order 2D polynomial. Displacement, warp, and tilt of the image plane may be corrected by adjustment of the gradient shimming currents. After correction, the accuracy of the geometric information is limited only by the pixel resolution of the image (= 1 mm). Precise definition of the target volume could be performed by the therapist either directly in the MR images or in calculated projection MR angiograms obtained by a maximum intensity projection algorithm. MR angiography provides a sensitive, noninvasive 3D method for defining target volume and critical structures, and for calculating precise dose distributions for radiosurgery of cerebral arteriovenous malformations. PMID- 1501532 TI - A fast T1 algorithm. AB - Multispectral tissue classification using magnetic resonance T1, T2, and rho images may be useful in diagnosing and locating certain pathology. Techniques for generating the T1 images necessary for this classification scheme often require longer data collection and post processing times than are practical. As a consequence, further development of this classification scheme may be limited. This paper addresses an improvement in the post processing time required to generate T1 images. A nonlinear least-squares algorithm is described for rapidly generating spin-lattice relaxation time images from variable repetition time magnetic resonance images. The algorithm generates a 256 x 256 pixel T1 image from nine variable repetition time images in approximately 60 sec on a VAX-6510 computer. PMID- 1501533 TI - Motion artifact suppression: a review of post-processing techniques. AB - Patient motion during data acquisition in magnetic resonance imaging causes artifacts in the reconstructed image, which for two-dimensional Fourier transform imaging techniques appear as blurring and ghost repetitions of the moving structures. While the problem with intra-view effects has been effectively addressed using gradient moment nulling techniques, there is no corresponding technique for inter-view effects with equal effectiveness and general applicability. A number of techniques have been proposed for correcting the inter view effects, and these may be divided into those that minimise the corruption of the data, and those that post-process the data to restore the image. The techniques in the former category are briefly reviewed, then those in the latter category are examined in detail. These are analysed in terms of motion model, model parameter estimation, and data correction. PMID- 1501534 TI - High density barium sulfate suspension for MRI: optimization of concentration for bowel opacification. AB - In this in vitro study of a potential oral MRI contrast agent, barium sulfate suspension (BSS), the object was to examine the effect of varying barium sulfate concentration on signal intensity while keeping suspension additives the same; and to optimize the concentration of a specific preparation of BSS. A phantom was used to test suspensions with concentrations of barium sulfate ranging from 90% to 220% w/v. T1-weighted, T2-weighted, and gradient echo sequences all showed a decrease in signal as concentration was increased to 170%. Between 170% and 220%, the signal intensity was constant on the T1-weighted and T2-weighted sequences. With the proton density and gradient echo sequences, there was a slower rate of decline in the signal intensity in the 170 to 220% range of BSS concentrations. We conclude that BSS with a concentration in the range of 170% to 220% w/v is optimum for the specific preparation used. We speculate that the behavior of the signal-to-noise ratio with changing concentration is explained by factors including proton density, T1 relaxation enhancement, diffusion effects, and magnetic field inhomogeneity, depending on the particular pulse sequence used. PMID- 1501535 TI - Dissociation of gadolinium chelates in mice: relationship to chemical characteristics. AB - Tissue distributions of seven 153Gd-labeled Gd chelates were determined at five residence intervals (5 min to 14 days) following intravenous administration of 0.4 mmol/kg to mice. Relationships were sought among physicochemical parameters: thermodynamic and conditional (pH 7.4) equilibrium stability constants (log K and log K'), acid dissociation rate constants (k(obs)), lipophilicity (log P), overall charge, and size (molecular weight). Size and lipophilicity did not correlate with tissue distributions. There were possible correlations between anionic charge and rapid, early renal excretion and between stability constants and long-term residual Gd deposition. Strong correlations (r greater than 0.99) were found between acid dissociation rates and long-term deposition of Gd in the whole body, liver, and femur. This is attributed to dissociation of Gd from the chelates in vivo. Acid dissociation rates may be useful in predicting dissociation of Gd from chelates in vivo. PMID- 1501536 TI - Localized phosphorus NMR spectroscopy: a comparison of the FID, DRESS, CRISIS/CODEX, and STEAM methods in vitro and in vivo using a surface-coil. AB - The FID, DRESS, CRISIS/CODEX, and STEAM techniques for localized 31P NMR spectroscopy were compared using a Siemens Magnetom SP63 1.5 T whole-body imager and a surface-coil, 80 mm in diameter, acting as transmitter and receiver coil. The comparison was performed with phantom experiments and human in vivo investigations on the calf muscle. The phantom experiments which used the same volume size showed a comparable signal-to-noise ratio for FID and DRESS, while the two fully localized techniques showed a reduction in signal-to-noise ratio to 76% for CRISIS/CODEX and 31% for STEAM. The in vivo measurements confirm the phantom results and reveal that CRISIS/CODEX gains a 2.5 fold higher signal-to noise ratio than STEAM under the same conditions. PMID- 1501537 TI - Ethanol-induced fatty liver in the rat examined by in vivo 1H chemical shift selective magnetic resonance imaging and localized spectroscopic methods. AB - In vivo 1H magnetic resonance imaging (MRI), chemical shift selective imaging (CSI), and localized (VOSY) 1H magnetic resonance spectroscopy (MRS) were used to study fatty infiltration in the livers of rats chronically fed an ethanol containing all-liquid DeCarli-Lieber diet. Conventional total proton MRI showed a somewhat hyperintense liver for ethanol-fed rats, compared with pair-fed controls. CSI showed a dramatic increase in the fat signal intensity for ethanol treated rats that was fairly homogeneous throughout the liver. However, CSI also showed a substantial decrease in the water signal intensity for the ethanol treated rats compared to pair-fed control rats. 1H VOSY MR spectra also showed a 5.5-fold increase in the methylene resonance (1.3 ppm) of fat and a 50-70% decrease in the water resonance (4.8 ppm). Relative in vivo proton T1 and T2 relaxation times for the water resonance separate from the fat resonance, determined from modified VOSY experiments, were found to tend to increase and decrease, respectively, for ethanol-treated rat livers compared with controls. The decrease in hepatic water signal intensity could be accounted for by the decrease in T2 and decrease in water density due to the presence of accumulated hepatic fat (approximately 25 mg/g wet weight of liver). When ethanol was withdrawn from the chronically treated rats, fatty infiltration was observed by both CSI and VOSY spectra to revert toward control values with a half-life of 2-4 days. By day 16, however, the signal intensity for hepatic fat was still significantly higher than control levels. In vitro 1H MRS studies of chloroform methanol extracts confirmed the 5.5-fold increase in total hepatic fat induced by the chronic ethanol treatment, and showed further that triacylglycerols were increased 7.7-fold, cholesterol was increased fourfold, and phospholipids were increased 3.3-fold, compared with liver extracts from pair-fed control rats. PMID- 1501538 TI - Use of 1H/23Na and 1H/31P double frequency tuned birdcage coils to study in vivo carbon tetrachloride-induced hepatotoxicity in rats. AB - In vivo 1H and 23Na magnetic resonance imaging (MRI) and 31P magnetic resonance spectroscopy (MRS) techniques were used to study CCl4-induced acute hepatotoxicity in rats in situ. One or two hours following exposure to CCl4, a localized edematous region was detected in the liver by 1H MRI. The CCl4-induced edema was localized in a region surrounding the hepatic portal vein. With the use of a 23Na/1H double frequency tuned bird-cage imaging coil an increase in Na+ ion flux was also observed in the same region as the edematous region detected by 1H MRI. Pretreatment with alpha-phenyl-tert-butyl nitrone (PBN), a free radical spin trap, 30 min prior to CCl4 exposure, was found to reduce the CCl4-induced edematous response in the liver observed in either 1H or 23Na-NMR images. Inhibition of the CCl4-induced edematous response in rat liver by PBN demonstrates that free radical intermediates, arising from the metabolism of CCl4, are possibly the key causal agents in the initiation of the edematous response. In addition, with the use of a 31P/1H double frequency tuned bird-cage imaging/spectroscopy coil, localized 31P spectra (ISIS) were obtained from the regions of CCl4-induced "tissue damage" observed in the 1H-MRI images. The most notable changes observed from the 31P spectra were an increase in inorganic phosphate (Pi) and a decrease in hepatocytosolic pH in the CCl4-treated rat livers in comparison to saline-treated control livers. PMID- 1501539 TI - Bio-effects of high magnetic fields: a study using a simple animal model. AB - The desire to do clinical imaging and spectroscopy at magnetic field strengths greater than 2 Tesla (T) necessitates investigation of possible bioeffects at these high fields. A simple T-maze was utilized to evaluate the aversive effects of exposure to three levels of static magnetic field (0, 1.5, and 4 T). The right arm of the maze extended into the center of a 30-cm horizontal bore magnet, while the left arm extended into a mock magnet bore with the same dimensions. The self shielded design of the magnet reduces the fringe field to zero within 1 m of the bore, placing the start box of the maze outside the 5-G line of the magnet. Each rat performed a total of ten trials at each level of magnetic field strength. A follow-up subset was run at 4 T with the maze reversed. At 0 T, the rats entered the magnet freely. No significant differences from the control were observed at 1.5 T. At 4 T, however, in 97% of the trials the rats would not enter the magnet. In the maze-reversed subset a majority of the rats turned toward the magnet, indicating that they had learned an aversive response from the previous trials at 4 T. However, in only 4 decisions out of 58 did the rats actually enter the magnet. Eighteen decisions to turn around were made at the edge of the magnet in a region of strong field gradients (up to 13 T/m) and a field strength up to 1.75 T.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1501540 TI - Artifacts in chemical shift selective imaging. AB - The role of susceptibility effects in the production of artifacts in chemical shift images generated by the selective excitation technique is discussed. The effects are demonstrated in images of phantom samples of agarose gels containing small air bubbles. The artifacts can lead to erroneous interpretations, in which the resonances to be resolved exhibit a relatively small chemical shift separation, such as that between water and soluble carbohydrates (sugars). PMID- 1501541 TI - MR imaging of diplomyelia. AB - We present an unusual case of duplication of the fifth lumbar vertebra and sacrum in a 6-year-old boy. The spinal cord was also duplicated and tethered by bone spurs bilaterally. The imaging features and the embryological basis of diplomyelia are discussed. PMID- 1501542 TI - MR appearance of intra-abdominal metastatic melanoma. AB - We present a case illustrating the magnetic resonance (MR) features of a large retroperitoneal metastatic melanoma. MR characteristics of intra-abdominal metastatic melanoma have not been reported previously. We report MR features similar to those reported for melanoma metastatic to other sites. PMID- 1501543 TI - [AIDS in Italy: update to December 31, 1991]. PMID- 1501544 TI - [AIDS in the world, up to October 1, 1991]. PMID- 1501545 TI - [Cognitive-behavioral model and instruments of evaluation. Organization of a rehabilitation center]. AB - The Authors describe the one year experience they had at A.MI.G a rehabilitation centre in Florence. Problems of organization and evaluation are considered. Methods of evaluation have been used to divide the patients in three groups which have been treated differently. Rehabilitating interventions based on verification and therapeutic continuity are shown. Problems which have arisen and considerations on the hypothetic future interventions are considered. PMID- 1501546 TI - [Revival of convulsive therapy]. AB - After a brief review of the history of convulsive therapy, the paper criticises the denigratory campaign which was directed against this form of therapy for many years in Italy and later abroad. It stresses that convulsive therapy is now used worldwide, in spite of a few justifiable restrictions, for these indications and that the risks involved in the therapy itself, which are minimum, have been reduced. The Authors complain that this revival, which is now spreading internationally, has been hardly felt in Italy, especially in university circles. PMID- 1501547 TI - [Primary community health districts and changes in the utilization of a psychiatric service for diagnosis and therapy]. AB - The Authors analyze the activity of Pavia's General Hospital Psychiatric Unit over a ten year period. Data, presented as rates standardized by sex and age, are processed according to patients' residential socio-health districts. The analysis of the results shows marked differences in the Service utilization among different districts. Correlations between these differences and some socio demographic and clinical variables enable the Authors to put forward some hypotheses in order to understand this pattern of Service utilization. In particular, "high-users" and patients with a past history of admissions to psychiatric hospitals tend to be found especially in the districts which provide the Service with a heavy workload. A closer attention to these patients and to their pathways to care will enable the Service staff to optimize its supply of care and to plan new kinds of treatments. PMID- 1501548 TI - [The etiological problem of schizophrenia]. AB - The originality and heterogeneity of hyperthese on the aetiologies of schizophrenia continue to make this entity debatable an uncertain. From the study of the numerous, discordant hypotheses that have accompanied schizophrenia this century, the need emerges for scientific thought that takes in the relativity of single theories and transcends them in a momentaneous suspension of judgment. PMID- 1501549 TI - [Culture and alcoholism]. AB - The paper examines the varying importance which has been attributed to alcohol in different periods and emphasis that today cultural attitudes towards alcohol and alcoholics are becoming increasingly ambiguous: there is growing difference towards teetotallers and substantial permissiveness towards drinkers. This incongruous attitude even goes so far as to romanticise the death of several artists from alcoholism. PMID- 1501550 TI - [Analytical psychology and philosophy]. PMID- 1501551 TI - [Epidemiologic psychiatric investigation in the community health district of Avezzano]. AB - The aim of the epidemiological psychiatric survey carried out among the users of the Mental Hygiene Centre of Avezzano local health district was to study the socio-demographic and clinical characteristics of participants. Data for patients for the years 1979 and 1989 were collected and analysed by studying all clinical records registered during those periods. This choice reflected the need compare user characteristics and methods of using the service following the introduction of the reform decree no. 180/1978. The aim of this retrospective epidemiological survey was to obtain data and information which would serve to formulate answers which responded to the needs expressed by users. The results revealed a heterogenous territorial distribution of psychiatric cases and this provided some indication for the realisation of a complex network of psychiatric network in the Avezzano health district. PMID- 1501552 TI - [Schizophrenia and multiple sclerosis]. AB - On the basis of published data on the frequent incidence of psychiatric disorders in demyelinating diseases, the paper report the case of a 22 year old patient who was brought to the Authors' attention with a schizophrenia-type disorder, with prevalently negative symptoms, and suffering from the advanced stages of a demyelinating pathology. Anamnestic and clinical characteristics reported by other Authors were also evident in this patient: the absence of familiarity for schizophrenic disorders, the absence of earlier psychiatric pathologies, the constant progress of psychosis and limited response to pharmacological therapy. The main results of clinical and instrumental tests are discussed. PMID- 1501553 TI - [Medico-social aspects of AIDS]. AB - The AIDS crisis has brought us face to face with complex medical and social challenges unparalleled in this century. The magnitude of this tragic epidemic is measured not only in the cost in human lives, but also the enormous financial burdens of health care and lost productivity which each and every one of us, as well as future generations, will ultimately bear. This article presents an opportunity to explore a variety of health, social, economic, juridical and working issues of AIDS. PMID- 1501554 TI - [Study of acute psychoses. I. The problem of acute psychoses: nosographic classification]. AB - Survey of the first admitted patients for nonorganic and nonaffective acute psychotic decompensation in an Inpatient Treatment Unit, as a part of a Mental HealthCenter, in a General Hospital. Preliminarily the Authors review the concept of "acute psychosis" from Bleuler to Leonhard, Wyrsch, Lanfeldt, the bouffees delirantes of the French literature, the schizophreniform disorder of the DSM III R. The acute psychosis is "a carrefour state" where many types of acute events come together: schizophrenic, affective, reactive. Sometimes, but rarely, acute psychosis is a nosographic unit. This unit needs further evidence. PMID- 1501555 TI - [Mental retardation and psychiatric pathology. Statistical investigation and follow-up]. AB - The Authors describe the organization and aims of the rehabilitation institute "G. Ferrero" of Alba, Cuneo district, Italy. Afterwards they present, analyse and compare 34 items regarding patients over 14 years of age that were present on the 30 November 1978 and 1988. The most important data are: 1) a large rise in average age and stay at the institute; 2) a similar rise in the mental retardation level; 3) the lack of link between handicap level and possibility for the subject to go back to the original family; 4) a considerable increase in the subjects with psychosis or cerebropathia; 5) the poor prognosis for psychotic subjects, that are affected 10 years after and almost never succeed in going back to their original family or in finding a job; 6) big changes that changing types of patients produced in the institute's aims and in treatment, with partial renunciation to rehabilitation and development of nursing and ergotherapy. PMID- 1501556 TI - The effects of closed-head injury on postural sway. AB - The purpose of this study was to determine the effects of closed-head injury upon postural sway. Forty-eight subjects (26 males and 22 females) between the ages of 18 and 45 were equally divided into four groups corresponding to their level of head injury. Group 1 had not incurred a head injury, group 2 members incurred head injuries but did not lose consciousness, group 3 lost consciousness for less than 6 h, and group 4 lost consciousness for greater than 6 h. All subjects were at least 1 yr postinjury. Each subject performed three trials of six variations of the Romberg test. The center of pressure transmitted through the bottom of the feet was monitored during each 30-s trial. Total, anterior-posterior (AP), and medial-lateral (ML) sway was calculated from center of pressure data. The severely head-injured group generally evidenced greater AP sway than the other three experimental groups for all but one test condition. It was concluded that closed-head injury, particularly when associated with relatively long periods of unconsciousness, results in postural instability. PMID- 1501557 TI - An analysis of supraspinatus EMG activity and shoulder isometric force development. AB - Injury to the shoulder represents a significant disability to the athlete participating in throwing and other overhead sporting activities. There are few scientifically based rehabilitation protocols regarding the most efficient exercises for the rotator cuff musculature. There is contradiction concerning the most efficient position for supraspinatus muscle electromyographic (EMG) activity. Because the supraspinatus is the most frequently injured musculotendinous structure of the shoulder, the most efficient position for testing and rehabilitation of this structure should be identified. The purposes of this study were to compare two test positions for supraspinatus EMG activity and maximal voluntary isometric contraction (MVIC) force development of the shoulder. Twenty-two subjects performed MVIC in the two recommended testing positions. A paired t-test revealed the prone position produced significantly greater (P = 0.04) EMG activity than the standing test position. An additional paired t-test revealed the standing position produced significantly greater (P = 0.0001) force than the prone position. Since the supraspinatus EMG activity was lowest in the position that produced the greatest shoulder MVIC force, we hypothesize that muscle substitution occurred. We recommend the prone position for supraspinatus rehabilitation and testing. PMID- 1501558 TI - Isometric exercise training lowers resting blood pressure. AB - Both rhythmic and "resistive" (weight lifting) exercise training can produce modest decreases in resting blood pressure. The next logical point along an exercise continuum consisting of different proportions of rhythmic and isometric efforts is a strictly isometric effort. The purpose of these studies was to assess the effects of isometric, handgrip exercise training on resting blood pressure. To avoid the extreme pressor responses elicited by fatiguing isometric efforts, the isometric exercise training used in this study consisted of brief handgrip contractions separated by rest periods. Modest repeated rises in systolic and diastolic pressures therefore served as the putative stimuli for training adaptations in resting blood pressures. Human subjects in study 1 trained with four, 2-min isometric handgrip contractions with 3-min rests between contractions. The intensity of the contractions was equal to 30% of their maximal effort for each day. The bouts of isometric exercise were performed three times per week for 8 wk. Study 2 training consisted of four contractions of 50% of maximum effort held for a duration of 45 s with 1-min rests. These were performed 5 d.wk-1 for 5 wk. In Study 1, all eight trained subjects had a significant decline in both systolic and diastolic resting blood pressures, with group averages of 12.5 and 14.9 mm Hg, respectively. Seven matched control subjects who did not train had no change in resting pressures. In study 2, subjects were trained in their home or workplace and experienced significant mean declines in resting systolic and diastolic pressures of 9.5 and 8.9 mm Hg.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1501559 TI - Growth and menarcheal status of elite female gymnasts. AB - The growth and maturity status of 201 elite female gymnasts was considered. The subjects were participants at the 24 World Championship Artistic Gymnastics in 1987. In addition to age at menarche, weight, stature, biacromial, and bicristal breadths, the sitting height/stature ratio, and the Health-Carter anthropometric somatotype of gymnasts 13-20 yr of age were compared with reference data for a nationally representative sample of Flemish girls. Median age at menarche (probit analysis) in gymnasts is 15.6 +/- 2.1 yr compared with 13.2 +/- 1.2 yr in Flemish girls. Anthropometric dimensions increase with age until about 16 yr and then tend to plateau. In contrast to body size, there is little variation in somatotype with age. Compared with adolescent girls, elite gymnasts are considerably shorter and lighter with narrower shoulders and hips, but the differences are more apparent after 17 yr. Elite gymnasts do not differ from nonathletes in relative leg length, but they have proportionally broader shoulders relative to hips. Differences in somatotype occur primarily in endomorphy (especially lower in gymnasts) and to a lesser extent in mesomorphy (higher in gymnasts). PMID- 1501560 TI - Estradiol and progesterone during exercise in healthy untrained women. AB - Ten eumenorrheic nonathletic women, aged 21-25, were studied on the 8th day following the LH peak in three consecutive cycles. Plasma level and metabolic clearance rate (MCR) of estradiol (E2) and progesterone (P) were measured before and during a 2-h continuous treadmill test at a speed corresponding to 70% of their running speed at anaerobic threshold on three separate occasions. A significant decrease of plasma level of the hormones (-30% and -40%, respectively, P less than 0.01; mean) from resting values was found, while their metabolic clearance rate increased significantly [E2-MCR from 1017 l.d-1 to 1312 l.d-1 (+29%), P less than 0.001; mean; P-MCR from of 2061 l.d-1 to 2988 l.d-1 (+45%), P less than 0.003; mean]. The increase in MCR of the two hormones was significantly correlated with the increase in heart rate and systolic blood pressure accompanying the beginning of the exercise test. PMID- 1501561 TI - The effect of normoxic or hypobaric hypoxic endurance training on the hypoxic ventilatory response. AB - Cross-sectional studies in endurance athletes have demonstrated a diminished hypoxic ventilatory response (HVR) compared with mountaineers or sedentary controls. Conversely, short-term altitude acclimatization may increase the HVR. The longitudinal effect of training, either at sea level or altitude, on HVR has not been previously reported. We therefore studied 21 untrained men and women before and after 5 wk of cycle ergometer training at either sea level or 2,500 m. HVR was determined using the steady-state method (16). Minute ventilation (VE) was measured with a Tissot spirometer during the last minute of 5 min breathing room air, 8% and 12% O2, administered in random order. CO2 was added at the mouth in an effort to maintain end-tidal CO2 at baseline levels. Oxyhemoglobin saturation was measured directly from arterial blood with a hemoximeter (OSM 3). HVR was defined as the positive slope of the line relating VE to O2 saturation in l.min-1%-1. One group of subjects trained at sea level at 70% maximal oxygen uptake (VO2max; N = 7). A second group trained at 2,500 m in a hypobaric chamber, at the same relative exercise intensity (i.e., 70% altitude VO2max) or same absolute intensity (same power output) as group 1 (N = 14). Both groups trained on a bicycle ergometer for 45 min.d-1, 5 d.wk-1 for 5 wk.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1501562 TI - Sweat electrolyte loss during exercise in the heat: effects of gender and maturation. AB - Humans may lose large amounts of water and electrolytes from sweat during prolonged exercise in a hot climate. Gender and maturational differences for the total sweat electrolyte losses have not been reported. The purpose of this study was to compare sweat electrolyte losses of prepubescent (PP), pubescent (P) and young adult (YA) males and females, under the same environmental conditions and relative exercise intensities. Twenty-five females (8 PP, 9 P, 8 YA) and 26 males (10 PP, 8 P, 8 YA) cycled for two 20-min bouts at 50% of their peak VO2 in a climatic chamber (42 degrees C, 18% relative humidity). Sweat was collected from a plastic bag attached to the lower back. Total body sweat loss was calculated from the differences in nude body weight corrected for fluid intake, urine, and respiratory water loss. Sweat [Na+] and [Cl-] tended to increase with maturation while sweat [K+] was lower in YA compared with that of PP. Children had a lower sweating rate than YA, even when corrected for body surface area. As a result, total Na+ and Cl- losses per kg body weight from sweat (mEq.kg-1.h-1) were higher in YA compared with those of PP and P; however, no maturational difference was found in K+ losses. Within the same maturational group, there were no gender differences in any of the electrolyte losses. These results may be useful in recommending "optimal" fluid-electrolyte drinks for children exercising in the heat. PMID- 1501563 TI - Cycling efficiency is related to the percentage of type I muscle fibers. AB - We determined that the variability in the oxygen cost and thus the caloric expenditure of cycling at a given work rate (i.e., cycling economy) observed among highly endurance-trained cyclists (N = 19; mean +/- SE; VO2max, 4.9 +/- 0.1 l.min-1; body weight, 71 +/- 1 kg) is related to differences in their % Type I muscle fibers. The percentage of Type I and II muscle fibers was determined from biopsies of the vastus lateralis muscle that were histochemically stained for ATPase activity. When cycling a Monark ergometer at 80 RPM at work rates eliciting 52 +/- 1, 61 +/- 1, and 71 +/- 1% VO2max, efficiency was determined from the caloric expenditure responses (VO2 and RER using open circuit spirometry) to steady-state exercise. Gross efficiency (GE) was calculated as the ratio of work accomplished.min-1 to caloric expenditure.min-1, whereas delta efficiency (DE) was calculated as the slope of this relationship between approximately 50 and 70% VO2max. The % Type I fibers ranged from 32 to 76%, and DE when cycling ranged from 18.3 to 25.6% in these subjects. The % Type I fibers was positively correlated with both DE (r = 0.85; P less than 0.001; N = 19) and GE (r = 0.75; P less than 0.001; N = 19) during cycling. Additionally, % Type I fibers was positively correlated with GE (r = 0.74; P less than 0.001; N = 13) measured during the novel task of two-legged knee extension; performed at a velocity of 177 +/- 6 degrees.s-1 and intensity of 50 and 70% of peak VO2 for that activity.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1501564 TI - Carotid-cardiac baroreflex response and LBNP tolerance following resistance training. AB - The purpose of this study was to examine the effect of lower body resistance training on cardiovascular control mechanisms and blood pressure maintenance during an orthostatic challenge. Lower body negative pressure (LBNP) tolerance, carotid-cardiac baroreflex function (using neck chamber pressure), and calf compliance were measured in eight healthy males before and after 19 wk of knee extension and leg press training. Resistance training sessions consisted of four or five sets of 6-12 repetitions of each exercise, performed two times per week. Training increased strength 25 +/- 3 (SE)% (P = 0.0003) and 31 +/- 6% (P = 0.0004), respectively, for the leg press and knee extension exercises. Average fiber size in biopsy samples of m. vastus lateralis increased 21 +/- 5% (P = 0.0014). Resistance training had no significant effect on LBNP tolerance. However, calf compliance decreased in five of the seven subjects measured, with the group average changing from 4.4 +/- 0.6 ml.mm Hg-1 to 3.9 +/- 0.3 ml.mm Hg-1 (P = 0.3826). The stimulus-response relationship of the carotid-cardiac baroreflex response shifted to the left on the carotid pressure axis as indicated by a reduction of 6 mm Hg in baseline systolic blood pressure (P = 0.0471). In addition, maximum slope increased from 5.4 +/- 1.3 ms.mm Hg-1 before training to 6.6 +/- 1.6 ms.mm Hg-1 after training (P = 0.0141). Our results suggest the possibility that high resistance, lower extremity exercise training can cause a chronic increase in sensitivity and resetting of the carotid-cardiac baroreflex.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1501565 TI - Effects of a functional knee brace on the biomechanics of running. AB - The purpose of the study was to assess the biomechanical effects of a functional knee brace on joint moments of force and joint powers in the lower extremity during the stance phase of running in subjects with a previous ACL injury. Sagittal-plane film records and ground reaction force data were obtained from five previously injured subjects running with and without a functional knee brace and from five healthy subjects running without the brace. Inverse dynamics were performed on these data to obtain the moments of force and joint powers. The angular impulse in the extensor direction was assessed from each moment of force curve, and the work performed during selected portions of the stance phase was assessed from the joint power curves. ANOVA techniques on these variables indicated no significant differences between the brace and no-brace conditions in the previously injured subjects. In comparison with the healthy runners, the previously injured subjects had, on average, 49% and 32% greater extensor angular impulse about the hip and ankle (both P less than 0.05). In contrast, the healthy runners had, on average, 233% greater (P less than 0.05) extensor angular impulse about the knee. The corresponding negative and positive work performed at the knee were 321% and 191% larger (both P less than 0.05) in the healthy runners. The reduction in the extensor moment of force about the knee and the increase in the moments of force about the hip and ankle in the previously injured subjects reduced the stresses on the ACL and tibia while at the same time enabling them to run at the required speed. PMID- 1501566 TI - Timing of lower extremity joint actions during treadmill running. AB - It has been suggested that a disruption in timing between the subtalar and knee joints may be a possible mechanism for knee injury. It has also been documented that shoe construction can alter rearfoot motion. The purpose of the study was to describe the relationship between the subtalar and knee joint actions during the support phase of treadmill running while wearing different shoes. Twelve healthy subjects ran in each of three running shoes with unique midsole durometers (C1, 70; C2, 55; C3, 45). High-speed video (200 Hz) of the rear and sagittal views of each subject/condition were taken during the last minute of a 5-min run. Retro reflective markers were processed to determine the rearfoot angle and the sagittal view knee angle. The shoes were also subjected to a midsole material impact test. The impact test results indicated a linear trend in peak g and time to peak g across midsoles with the firmer midsole having a greater peak g and a shorter time to peak g. The results of the kinematic analysis indicated that there were no significant differences among the shoe conditions for the knee flexion parameters. However, there were significant differences in both the magnitude and the time to maximum pronation between the two firmer midsole conditions (C1 and C2) and the softer midsole condition (C3), indicating a nonlinear trend for these parameters. The softer midsole exhibited greater pronation values and a shorter time to maximum pronation.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1501567 TI - Effect of macronutrient composition of an energy-restrictive diet on maximal physical performance. AB - Thirty-six sedentary, mildly obese (30-40% fat), premenopausal women (29-49 yr) were randomly assigned to one of two dietary regimens for an 8-wk double-blind, parallel study of the effect of moderate caloric restriction and macronutrient variation on maximal physical performance. Group 1 (N = 19) consumed 4186 kJ.d-1 (1000 kcal.d-1) with a diet composition of 40% fat, 40% carbohydrate (CHO), and 20% protein. Group 2 (N = 17) also consumed 4186 kJ.d-1 but varied the percent kilojoules to 20% fat, 60% CHO, and 20% protein. Maximal aerobic power was measured using a modified Balke protocol, strength was assessed using isotonic bench and leg press machines and a Cybex 340 isokinetic device during knee flexion and extension, and muscular endurance was taken as the number of sit-ups performed in 1 min. Pre- to post-testing revealed significant (P less than or equal to 0.05) reductions in body weight (group 1, -7.4 kg; group 2, -6.5 kg) within both groups. No significant changes were seen in maximal aerobic power within both groups. Strength measures for both groups showed a trend toward reduction but statistical significance was only evident in right knee extension for group 1 and left knee extension for group 2 (P less than or equal to 0.05). Sit-up number increased nonsignificantly for both groups. Between group differences were not found in any body weight, body composition, or physical performance index. We therefore conclude that in mildly obese women, maximal exercise performance is relatively unimpaired after 8 wk of caloric restriction with either of two diets differing moderately in their macronutrient content. PMID- 1501568 TI - Effect of iron supplementation on endurance capacity in iron-depleted female runners. AB - The purpose of this investigation was to examine the effects of oral iron supplementation on endurance performance in initially iron-depleted, nonanemic female distance runners. Eighteen iron-depleted (serum ferritin less than 20 ng.ml-1, hemoglobin greater than or equal to 12 g.dl-1) women (22-39 yr) performed a VO2max test and an endurance run to exhaustion. Subjects were pair matched on the basis of endurance time and then randomly assigned to an iron supplement or a placebo group. Following supplementation, the iron group had a significantly higher (P = 0.03) mean serum ferritin concentration (23.4 vs 15.7 ng.ml-1) and lower (P = 0.04) mean total iron-binding capacity than the placebo group. Both groups increased their time to exhaustion (25.5% and 22.2% for the iron and placebo groups, respectively) but were not significantly different (P = 0.72) from each other. There were also no differences (P greater than 0.05) between the groups with respect to lactate concentrations and physiological measures taken during the two exercise tests. The results of this study suggest that 8 wk of oral iron supplementation improves iron status in iron-depleted female distance runners, but does not enhance endurance capacity. PMID- 1501569 TI - A technique for locating the center of mass and principal axes of the lower limb. AB - The position of the human body in space is typically recorded using a fixed inertial coordinate system, often referred to as a laboratory coordinate system. Although these fixed reference axes simplify the collection and reduction of such position data, the results produced often have little or no anatomical significance. The purpose of this study was to develop the methods, both experimental and analytical, to construct a set of orthogonal principal axes for each the foot, shank, and thigh segments of the lower limb for use in motion analysis. The axes chosen were determined by targeting specific bony landmarks as suggested by the literature and forming the principal axes with respect to these landmarks. The location of the center of mass of each segment was also determined from these anatomical landmarks. It was found that the foot, due to its less rigid nature and more complex geometry, required a more extensive analysis using a single frame of standing data prior to the analysis of the motion data. The axes formed do not attempt to solve the problems of joint rotation axes, but provide an initial, anatomically significant set of reference axes that may be easily reproduced and utilized in further analyses. PMID- 1501570 TI - Body composition of healthy sedentary and trained, young and older men and women. AB - This study examined the effects of age and physical activity on body composition and fat distribution by comparing differences between young and older endurance trained men and women with differences between young and older sedentary people. Although indices of total body adiposity (fat mass, percent body fat) were higher in the older than in the young people in both the trained and the sedentary groups, the magnitude of the difference was markedly less in the trained group (P less than 0.01). The average differences in fat mass between young and old sedentary men and women were 10.1 kg and 12.2 kg, respectively, but only 4.3 kg and 5.5 kg in trained men and women. Skinfold thicknesses were approximately 24% and approximately 47% larger at all sites (triceps, thigh, subscapula, pectoralis, umbilicus, suprailiac) in the older than in the young trained men and women, respectively. Similar differences were found between young and older sedentary people except at central, upper body sites, where the relative differences in skinfold thicknesses between young and older sedentary people were 2- to 6-fold greater than in trained people. Thus, people who exercise regularly appear to accumulate less adipose tissue in upper, central body regions as they get older, potentially reducing the risk for the metabolic disorders associated with upper body obesity. PMID- 1501571 TI - Physical conditioning among HIV-positive men. PMID- 1501572 TI - Local induction of tumor necrosis factor as a molecular mechanism of mucosal damage by gonococci. AB - Tumor necrosis factor (TNF) is an endogenously produced cytokine that plays a critical role in mediating septic shock and multi-organ failure, but previous studies of the role TNF in disease have not examined its role in mucosal disease processes. In an experimental model of acute gonococcal salpingitis, gonococcal infection of human fallopian tube mucosa resulted in increased mucosal production of TNF. Recombinant human TNF-alpha damaged fallopian tube mucosa in a dose response manner and produced epithelial damage with the same ultrastructural features as those observed in gonococcal infection. Blocking production of TNF during gonococcal infection diminished the extent of damage to fallopian tube mucosa. In addition to mediating systemic disease, such as septic shock, TNF is also produced locally, and can play a critical role in mediating mucosal disease processes, such as acute gonococcal salpingitis. PMID- 1501573 TI - Serum TNF alpha inhibitor in mouse typhoid. AB - Administration of anti-TNF alpha antiserum enhanced a sublethal infection with salmonellae of moderate virulence (Salmonella typhimurium M525) in innately susceptible (Ity(s)) BALB/c mice, indicating that TNF alpha is important in the early response which suppresses bacterial growth in the reticuloendothelial system (RES). However, only transient low levels of TNF alpha were detectable on day 3 in sera from some, but not all, sublethally infected mice. Conversely, on day 4 of the same infection, clear TNF alpha inhibitory activity was detected in some sera. Neither TNF alpha or any inhibitory activity were detected in sera of lethally infected BALB/c mice undergoing an acute, overwhelming Salmonella infection. In contrast, TNF alpha inhibitory activity, but not TNF alpha, was detected in sera of mice showing a cachectic syndrome induced by persistent high bacterial numbers following intravenous inoculation of a very high dose (2 x 10(7)) of the attenuated aro- S. typhimurium SL3261 strain. PMID- 1501574 TI - Receptor utilization by reovirus type 3: distinct binding sites on thymoma and fibroblast cell lines result in differential compartmentalization of virions. AB - Reovirus type 3/D infects cells following binding to specific cell-surface receptors. The characteristics of these receptors may play an important role in determining post-binding events critical to the viral life cycle. Some cell lines, i.e. L-cells, appear to bind reovirus type 3/D utilizing sialylated proteins as specific receptors for viral adsorption. Such binding results in productive infection. Other cell lines, i.e. R1.1 thymoma cells, bind reovirus type 3/D in a sialic acid independent manner which does not result in productive infection. Yet, a peptide analogue of the viral binding site is capable of inhibiting binding of reovirus type 3 to both cell types, suggesting the same viral epitope interacts with both cellular receptors. When binding of reovirus is studied by electron microscopy, the virus particles enter the L cells via coated pits, and are later seen in large accumulations in endocytic vesicles near the transGolgi network. In contrast, R1.1 cells appear to divert the reovirus particles to a cell membrane elaboration, with reovirus remaining bound to the cell membrane. At later time points with R1.1 cells, there are no apparent intracellular accumulations. These studies demonstrate that viruses can attach to different cells utilizing distinct receptors, and this may play a role in the ability of the virions to productively infect the cells. The capacity of virus to be adsorbed to cellular receptors which do not lead to internalization may be an important mechanism for the sequestration and clearance of virus. These observations have implications for the tissue tropism demonstrated by reovirus type 3/D and other viruses. PMID- 1501575 TI - Murine hypersensitivity pneumonitis: interleukin-4 administration partially abrogates the disease process. AB - C57BL-6 inbred mice were given intranasal instillations of Faeni rectivirgula (150 micrograms/day, 3 days a week for 3 weeks) to produce a lung inflammatory reaction which mimics Farmers' lung in humans. Challenged mice developed a strong inflammatory response in their lungs, based on various markers (lung index, bronchoalveolar cell number, fibrosis). The effect of interleukin-4 (IL-4) was studied by infusing mice intraperitoneally with 100, 1000 or 10,000 units of IL-4 weekly during the challenge period. It was shown that IL-4 infusion decreased the inflammatory response, as seen by a decreased lung index (1.7 in mice given F. rectivirgula and 10(3) U IL-4 and 1.31 in mice given antigen and 10(4) U IL-4 weekly versus 2.3 in mice instilled with F. rectivirgula). Interleukin-4 infusion also partially abrogated the F. rectivirgula-induced alveolitis, as seen by a decrease in cell numbers in the broncho-alveolar lavage (BAL) (1.3 x 10(5) cells in saline-instilled mice; 8.3 x 10(5) cells in mice given 10(3) U IL-4 and F. rectivirgula; 3.2 x 10(5) cells in mice given antigen and 10(4) U IL-4; 1.8 x 10(6) cells in mice given F. rectivirgula only). Also, it was apparent that IL-4 administration could partially block the appearance of the fibrosis induced by F. rectivirgula (220 micrograms of hydroxyproline/lung in challenged mice; 170 micrograms/lung in challenged mice given 10(3) U IL-4; 131 micrograms/lung in mice given antigen and 10(4) U IL-4 and c. 100 micrograms/lung in control animals). Infusion of 10(2) U IL-4 weekly had no statistical effect on any marker of inflammation.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1501576 TI - Expression of Bordetella pertussis filamentous hemagglutinin in Escherichia coli using a two cistron system. AB - Expression of Bordetella pertussis filamentous hemagglutinin (FHA) has been achieved in Escherichia coli K-12. This involved the construction of a two cistron system where the first cistron was provided by the NH2-terminus (first 98 amino acids) of MS2 polymerase. When the FHA gene sequences were fused to the first cistron, higher levels of expression were obtained and the fusion protein aggregated in inclusion bodies. FHA expressed by the two cistron system, however, appeared to be diffusely dispersed in the cytoplasm. PMID- 1501577 TI - A basic approach to periodontal diagnosis. PMID- 1501578 TI - A comprehensive approach to conservative periodontal therapy. PMID- 1501579 TI - Periodontal surgery. PMID- 1501581 TI - Oral implantology: a multidisciplinary approach. PMID- 1501580 TI - Supportive periodontal therapy. PMID- 1501582 TI - Periodontal prosthesis. PMID- 1501583 TI - Cefonicid potentiation of human macrophage activity. AB - This study was undertaken to evaluate the in vitro effects of cefonicid on phagocyte functions such as phagocytosis and intracellular killing of phagocytosed bacteria. At concentrations of half the MIC cefonicid caused human macrophages to ingest and kill Klebsiella pneumoniae at a greater rate than did drug-free macrophages. Bacteria pretreated with subinhibitory concentrations of cefonicid became more susceptible to the phagocytic and bactericidal activity of macrophages than untreated microorganisms. Sub-MIC cefonicid pretreatment of macrophages did not reduce phagocytosis and killing, confirming the inability of beta-lactam antibiotics to cross biological membranes. PMID- 1501584 TI - Studies on the epidemiology of child infections in the Bari area (south Italy). V. Epidemiology of Toxoplasma gondii infections. AB - Sera from 2790 0-15 aged infants and children were titrated for antibodies to Toxoplasma gondii by indirect immunofluorescent test. Maternal-derived antibodies were found at high rates in the first six months of life (32.9%). The positivity rate declined during the second semester of life (7.5%) and increased again with time (7.8% between 1 and 5 years, 11.2% between 5 and 10 years, 14.4% between 10 and 15 years). No statistically significant differences were found between the sexes. IgM specific antibodies were found at a titre of 1:32 or greater in 41 subjects (1.5%), who also exhibited IgG antibody titres ranging from 1:512 to 1:1024. Our results indicate a remarkable diffusion of toxoplasma infection in our area. PMID- 1501585 TI - Cytotoxic activity and IL-1 production in mice infected with Aspergillus niger. AB - In this report, we demonstrate an interaction between macrophages and T lymphocytes during A. nigr infection. Supernatants obtained after 48 hrs adherence of infected peritoneal macrophages were able to increase the cytotoxicity of T lymphocytes. Our results also indicate that macrophage supernatant (MS) from mice, in the first 5 days after challenge, is more active on T cell than MS produced later. Splenic T cells activated by IL-1 from mice at 5 days of infection show a significantly increased cytotoxicity, at 10 days after challenge, the cytotoxicity of T cells activated by IL-1 did not significantly differ from non-activated T cells. PMID- 1501586 TI - Comparison of three immunoassays for the rapid detection of bovine respiratory syncytial virus. AB - Three enzyme-linked immunosorbent assays (EIA) designed for the detection of human respiratory syncytial virus (RSV) were evaluated for the detection of bovine respiratory syncytial virus (BRSV) in bovine lungs and the results were compared with those obtained by a direct fluorescent antibody assay (DFA). The EIA tests used were Directigen EIA, Kallestad Pathfinder EIA, and Abbott RSV EIA. Homogenates of lung tissues obtained from 64 cattle that had died of respiratory disease were used; 32 were positive by DFA and 32 were negative. All EIA's varied in the amount of labor and time involved but their relative sensitivities were similar ranging between 59 and 66% when compared with DFA. The specificity of Pathfinder EIA was lower than those of the Directigen and Abbott tests. The overall agreement between the three EIA's and the DFA was 66-77% indicating that DFA is still the test of choice for detecting BRSV infection in lung tissues of cattle. PMID- 1501587 TI - Molecular cloning of a specific DNA probe for the identification of Bacillus licheniformis. AB - Bacillus licheniformis has been found to be one of the dominant nosocomial species of Bacillus: laboratories dealing with nosocomial infections must be able to identify Bacillus up to the species level. To date, no DNA probes have been isolated for B. licheniformis although there is a clear need for a direct detection by polymerase chain reaction. The isolation of a B. licheniformis specific DNA probe, as described in this paper, represents the first step toward accomplishing this goal. PMID- 1501588 TI - Density-dependent responsiveness to autocrine growth factors of Epstein-Barr virus transformed human B lymphocytes. AB - Analysis of the growth requirements of Epstein-Barr virus (EBV)-transformed B lymphocytes shows that interleukin 1 and thioredoxin, a disulfide reducing enzyme, are able to induce a marked increase in DNA synthesis in the early phases of in vitro culture. By contrast, interleukin 6 induces a steady increase in DNA synthesis comparable to that observed with crude conditioned supernatant. Furthermore, EBV-transformed B cells exhibit a density-dependent responsiveness to autocrine growth factors, thus suggesting that growth regulation of EBV transformed B cells might result from the interplay between different self stimulating soluble factors and from the competence of the cells to respond to autocrine growth factors. PMID- 1501589 TI - Possible relationship between Chlamydia trachomatis and acquired immunodeficiency syndrome. AB - This study suggests the possibility that the intracellular parasite Chlamydia trachomatis (Ct) may facilitate the transmission of the human immunodeficiency virus (HIV) during vaginal or rectal intercourse. This is based on the following findings: a) elevated titers of anti-Ct IgG are present in symptomatic acquired immunodeficiency syndrome (AIDS) patients; b) elevated titers of anti-Ct IgA are found in asymptomatic AIDS patients; c) low anti-Ct IgA titers were observed during the progression of the disease; d) high titers of anti-Ct IgA were found in patients suffering from autoimmune diseases; e) high levels of C3 fraction of the complement are found in many of the Ct patients. The presence of anti-Ct IgA and high C3 may be crucial since IgA inactivates Ct and C3 which may increase the invasion of HIV into the cells. This activity of IgA and C3 in Ct patients may increase the susceptibility of male homosexuals and other risk groups in the population to AIDS. PMID- 1501590 TI - Use of enzyme linked immunosorbent assay for estimation of antibody to Newcastle disease virus. AB - Serum antibody assay of 1045 serum samples from birds vaccinated with Newcastle Disease vaccine by HI test and ELISA was carried out. Five hundred and twenty seven birds were challenged with virulent virus and data on HI test, ELISA and challenge test results were used for comparison. A good correlation between HI titres, ELISA absorbance and potency was observed indicating the usefulness of ELISA for potency estimation of vaccines and determination of immunization level in vaccinated flocks. PMID- 1501591 TI - Aluminium, chromium and manganese detoxification mechanisms in Pseudomonas syringae: an X-ray fluorescence study. AB - Pseudomonas syringae cultured in a defined citrate medium supplemented with 1 mM aluminium, chromium and manganese, respectively, appeared to elicit disparate biochemical responses. At the stationary phase of growth aluminium was predominantly present as an insoluble residue. Although virtually none of this metallic element was detected in the supernatant, the bacterial cells appeared to contain some aluminium. Following the initial uptake of chromium the microbe secreted the metal in the supernatant. Only a small fraction of the chromium was localised in the bacterial cells; 91% manganese was biotransformed into an insoluble pellet. No citrate was detected in the exocellular fluid at cessation of cellular growth. PMID- 1501592 TI - Enzyme-linked immunosorbent assay for the detection of Fusobacterium necrophorum antibody in bovine sera. AB - An enzyme-linked immunosorbent assay (ELISA) with HCl heat extracted antigen of Fusobacterium necrophorum was developed for the detection of antibody in bovine sera. Optimal conditions for antigen concentration and dilution of bovine serum were established. Pretreatment of positive reference serum with the antigens of different bacteria demonstrated no decrease, whereas the serum pretreated with F. necrophorum antigens revealed a decrease in the ELISA values. The apparent difference in ELISA values was observed between the sera derived from cattle infected and not infected with Fusobacterium necrophorum. These findings indicate that the ELISA detects the antibody to F. necrophorum in bovine sera. PMID- 1501593 TI - Effect of seawater storage on coliforms, faecal coliforms and Escherichia coli. AB - The effect of refrigeration of seawater samples for 24 h prior to assaying coliforms, faecal coliforms and Escherichia coli was assessed. When the initial coliform counts were low, the amount of bacteria in refrigerated samples decreased. When the number of initial total coliforms was high, there was an increase following cold storage. E. coli counts also decreased. Faecal coliforms, when in the initial 200-500 count range, showed a decrease during cold storage but with good correlation (r = 0.9). In all other groups, no correlation between counts of before versus after storage was found. Assessment of seawater pollution following 24 h cold storage should not be made. PMID- 1501594 TI - Occurrence of haemolysin producing Aeromonas species in the aquatic environment. AB - A total of 532 environmental isolates of motile aeromonads were evaluated for their ability to produce haemolysins. Of those isolates tested, 68 (12.5%) and 18 (3.4%) were found to be alpha and beta haemolytic, respectively. Aeromonas caviae was found to be alpha haemolytic (3.8%) for the first time. Isolates of Aeromonas which were either alpha or beta haemolytic on plate assay also produced detectable amounts of haemolysin in cell free broth assay. PMID- 1501595 TI - Lactoferrin binding properties of Vibrio cholerae. AB - The lactoferrin binding properties of Vibrio cholerae, a non-invasive pathogen were investigated. Screening of fifty V. cholerae strains of different serogroups and serotypes, showed that 10% of the V. cholerae strains bound to 125I-labelled lactoferrin, and 40% of the 125I-labelled lactoferrin bound to V. cholerae strain 623 could be displaced by unlabelled lactoferrin. Other iron-binding glycoproteins and ferroproteins like ferritin, transferrin, haemoglobin, and myoglobin inhibited the binding of 125I-lactoferrin to a lesser degree. Monosaccharides (GalNac, Man, Gal, and Fuc), and other glycoproteins such as fetuin and orosomucoid also inhibited the binding to a lesser extent. V. cholerae 623 showed a cell surface associated-proteolytic activity which cleaved off the cell-bound 125I-labelled lactoferrin. The generation of cryptotopes on the V. cholerae cell surface by proteolytic digestion favoured the binding of ferritin, transferrin, haemoglobin, and haemin, as well as Congo red, to cells of V. cholerae 623. PMID- 1501596 TI - Bacterial uptake of 14C-chlorhexidine diacetate and 14C-benzyl alcohol and the influence of phenoxyethanol and azolectin: studies with gram-negative bacteria. AB - The uptake of 14C-chlorhexidine (14C-CHA) by Pseudomonas aeruginosa and smooth, rough and deep rough strains of Escherichia coli was very rapid with maximum uptake occurring within 20 s. Despite the rapid binding, the lethal action of CHA, although concentration-dependent, is comparatively slow and occurs in minutes rather than seconds. This indicates that the initial rapid binding is followed by a second slower action, responsible for the lethal effects of CHA. The lethal action could be accelerated, particularly at modest concentrations of CHA, by the simultaneous presence of phenoxyethanol (POE) or benzyl alcohol (BZA), although the magnitude of the effect was small. Both alcohols had little effect on the binding of 14C-CHA, which does not explain the enhanced bactericidal action of CHA. Uptake of 14C-benzyl alcohol (14C-BZA) by the same strains showed very different patterns with slower and time-related binding. CHA had a marked effect on BZA absorption but no direct link was established between binding patterns and cell death. The CHA neutraliser, azolectin, removed bound CHA (in the presence or absence of POE) very efficiently even at contact times of only 20 s. PMID- 1501598 TI - Digest of proceedings of the 1992 Michigan State Medical Society House of Delegates meeting. PMID- 1501597 TI - Regulation of intracellular osmotic pressure during the initial stages of salt stress in a salt-tolerant yeast, Zygosaccharomyces rouxii. AB - The accumulation of glycerol and inorganic ions as it related to osmotic pressure, and the regulation of intracellular osmotic pressure in a salt-tolerant yeast, Zygosaccharomyces rouxii, were examined for several hours after salt stress. Intracellular contents of glycerol increased for up to 6 h in media supplemented with 1 M and 2 M NaCl and did not increase in medium containing 3 M NaCl. Intracellular contents of Na+ and Cl- reached a maximum value within 1 and 3 h, respectively, in all NaCl-containing media and increases were proportional to the concentration of NaCl in the medium. As glycerol was accumulated in cells, the intracellular contents of Na+ and Cl- gradually decreased in media containing 1 M and 2 M NaCl. After salt stress, cell volume decreased within 1 h and the original volume was re-established for 3 to 6 h in media with 1 M and 2 M NaCl but not in medium with 3 M NaCl. Intracellular concentrations of solutes, which were calculated from the total contents of glycerol and inorganic ions and the cell volume, became almost equivalent to the external osmotic pressure within 1 h after salt stress. Experiments using various inhibitors showed that a large amount of ATP was required not only for the synthesis and accumulation of glycerol but also for the exclusion of Na+ and Cl- from cells under salt-stressed conditions. PMID- 1501599 TI - Humoral mechanisms in immune neuropathies. AB - Antibody and complement are implicated in the pathogenesis of a number of human, primarily demyelinating neuropathies. The ability of serum and purified, primarily IgM, antibodies to mediate demyelination was demonstrated in both in vitro and in vivo model systems. Complement activation to produce channel-forming terminal complement complexes, C5b-8 and C5b-9, was required for demyelination in vitro. Antibodies implicated in the demyelination of peripheral nerve of GBS patients and patients with monoclonal gammopathy-associated neuropathy bind carbohydrate epitopes on various neutral or acidic glycolipids and glycoproteins of peripheral nerve. In acute monophasic GBS, antibodies of multiple specificities may be induced to different infectious agents. These Ab, following penetration of a damaged blood-nerve barrier, are proposed to bind determinants of human peripheral nerve and participate in demyelination of nerve through activation of complement. These antibodies correlate with the clinical course, the generation of complement activation products, and the response to plasmapheresis. The mechanism by which the blood-nerve barrier is broken in GBS and other inflammatory demyelinating neuropathies and the extent of the role of the cellular immune system remain to be determined. Recent experiments demonstrated that T cells, antibody, and complement could synergistically contribute to central nervous system demyelination in naive rats. A similar synergism would be an attractive hypothesis for demyelination in the peripheral nervous system. PMID- 1501600 TI - Multifocal motor neuropathy. AB - We believe that our present understanding of these syndromes is insufficient to separate CIDP from MMN clearly and consider MMN to be a remarkably multifocal, predominantly motor variant of CIDP with the very unusual electrophysiologic feature of conduction block confined to motor axons. Further studies are clearly needed to clarify fully the relationship between CIDP and MMN and the relationship of MMN and other motor syndromes to various ganglioside antibodies. PMID- 1501601 TI - Participation in school physical education and selected dietary patterns among high school students--United States, 1991. AB - Inadequate physical activity and unhealthy dietary patterns (particularly diets high in fat and low in fruits, vegetables, and grains) established during youth may extend into adulthood and may increase risk for chronic diseases, such as coronary heart disease and cancer (1-5). This report examines the prevalence of self-reported enrollment, attendance, and participation in school physical education (PE) and examines selected dietary patterns among students in grades 9 12 from two school-based components of CDC's Youth Risk Behavior Surveillance System (6): 1) the national Youth Risk Behavior Survey (conducted during April May 1991) and 2) individual state and local Youth Risk Behavior Surveys (conducted by departments of education in 23 states and 10 cities during the same time). PMID- 1501602 TI - Lizard-associated salmonellosis--Utah. AB - During June 1992, CDC identified a rare Salmonella serotype, S. poano, from a stool specimen from an infant. The specimen was sent from the Utah Division of Laboratory Services. This report summarizes the epidemiologic investigation of this case. PMID- 1501603 TI - Publicly funded HIV counseling and testing--United States, 1991. AB - Human immunodeficiency virus (HIV) counseling and testing (CT) services provided by health departments are a major component of the national HIV-prevention program. The purpose of HIV CT is to 1) reinforce perception of risk by those who are unaware or uninformed, 2) help uninfected persons initiate and sustain behavior changes that reduce their risk for becoming infected, and 3) identify HIV-infected persons who can be referred for early medical care and counseled to practice safer behaviors. The use of publicly funded HIV CT has steadily increased; in 1991, nearly 2,091,000 HIV-antibody tests were performed, compared with approximately 79,000 tests in 1985. CT services are provided by health departments in 65 HIV-prevention project areas including the 50 states, the District of Columbia, six cities, and eight territories. Each calendar quarter, the programs report to CDC data regarding the number of pretest counseling sessions. HIV-antibody tests, positive tests, and posttest counseling sessions. Information is also provided on self-reported risk category, age group, sex, and race/ethnicity. This report summarizes data reported for 1991.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1501604 TI - Condom use among male injecting-drug users--New York City, 1987-1990. AB - Heterosexual transmission of human immunodeficiency virus (HIV) continues to increase, especially among injecting-drug users (IDUs) and their sex partners. During 1991, 22% of women with acquired immunodeficiency syndrome (AIDS) in the United States reported having had sex with a male IDU; this risk behavior was second to injecting-drug use (48%) as a transmission category for women. To better understand how to reduce heterosexual transmission of HIV, a study on condom use among male IDUs on the Lower East Side of Manhattan, New York City, was conducted as part of CDC AIDS Community Demonstration Projects. This report summarizes the results of that study.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1501605 TI - Surveillance of children's blood lead levels--United States, 1991. AB - Lead poisoning is one of the most common environmental pediatric health problems in the United States (1): in 1984, an estimated three to four million children had blood lead levels (BLLs) sufficiently high to adversely affect intelligence, behavior, and development (2). Because little is known about efforts to monitor BLLs among U.S. children, in 1991, the Council of State and Territorial Epidemiologists (CSTE) and CDC conducted a survey to characterize reporting requirements and data-collection activities for BLLs among U.S. children during 1989. This report summarizes the findings from that survey.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1501606 TI - Food and Drug Administration approval of a second diphtheria and tetanus toxoids and acellular pertussis vaccine. PMID- 1501607 TI - Models for embryonic periodicity. PMID- 1501608 TI - [Differential diagnosis of pediatric dyspnea]. PMID- 1501609 TI - [Are children philosophers? Opening address of the 87th annual congress of the German Society of Pediatrics]. PMID- 1501610 TI - [Pathogenesis of epilepsy in childhood and adolescence]. AB - After a short discussion of the basic mechanisms of epileptic reactions, the conditions for epileptrogenesis are reviewed. As demonstrated by studies in animal models, distinctive structural and neurochemical characteristics of the brain tissue, probably genetically determined, build a main precondition for seizure manifestation. Starting from these basic concepts, the multifactorial pathogenesis of human epilepsy is discussed with special regard to genetic factors. The seizure liability results from the interaction of several independently transmitted genetic and lesional factors. None of these traits are epileptogenic by themselves, but effective only in interaction with other pathogenetic factors. Genetically determined "normal" structural and functional properties of the brain, e.g. expressed by generalized alpha rhythm, are involved in the complex pathogenesis of epilepsy. From a neurobiological point of view, epilepsy is always a multifactorially determined disease. The nowadays usual separation of idiopathic and symptomatic types of epilepsy may be helpful for communication in daily practice, but represents a simplification under pathogenetic aspects. PMID- 1501611 TI - [Differential diagnosis of cerebral seizures]. AB - Several non-epileptic disorders may cause episodic and paroxysmal symptoms that resemble epilepsy and they must be considered in the differential diagnosis. Some of these disorders are discussed in the present review: vasovagal, vasomotor and cardiac syncopes, breath holding spells. Among the sleep disorders, parasomnias, nightmares and the benign neonatal sleep myoclonus are mentioned. Migraine with aura, alternating hemiplegia and benign vertigo of childhood are probably related disorders. Benign myoclonus of early infancy, paroxysmal choreoathetoses and pseudoepileptic or hysterical seizures are further non-epileptic attack disorders to be considered in the differential diagnosis. PMID- 1501612 TI - [Ophthalmoplegia interna after varicella]. AB - We present the case of a 5 1/2 year old girl. 14 days after the onset of the typical rash, the right pupil was dilated and fixed to light. Her manifest refraction was O.D. +1.0 dpt. No signs of iridocyclitis could be found, the fundus was normal. One year later, the pupil of the right eye was still dilated, whereas accommodation had slightly improved (+0.5 dpt). Internal ophthalmoplegia complicating chickenpox is rare, 13 cases have been reported so far. PMID- 1501614 TI - [Severe human bite injuries in a 7-day-old newborn infant]. AB - It is reported about a 7-day-old newborn showing considerable bite wounds in his face. Due to the evidence of blood group characteristics on his pajamas and by means of a dental impression, the 2 1/2-year-old brother was "found guilty" of having caused the injuries. During a short antibiotic treatment the bite wounds cleared, showing very good results. Jealousy is assumed to be the reason for the incidence. Based on a comprehensive and also child-psychiatric examination of the family, other reasons could be excluded. Similar cases of sibling violence with newborns, partly fatal, are reported in literature. If infants fear to loose the security of their homes, jealousy may lead to severe aggressive reactions. PMID- 1501613 TI - [Congenital anhidrotic ectodermal dysplasia in a female infant]. AB - Fever of unknown origin, unability to sweat, hypotrichosis, absent eyebrows and thick everted lips were symptoms in a 3 month old female infant and raised the suspicion of anhidrotic ectodermal dysplasia. After several days of high fever and enteritis our patient presented with convulsions which could hardly be interrupted for a couple of days. Two months later brain scanning revealed serious brain damage. Finally the diagnosis of anhidrotic ectodermal dysplasia was confirmed by the unability to sweat by means of the quantitative pilocarpin iontophoresis test. Skin biopsy showed absence of the eccrine glands. PMID- 1501615 TI - [Etiology and diagnosis of cerebral infarcts after the neonatal period]. AB - QUESTION: After the neonatal period, cerebral infarctions are very rare in childhood. In the present study we aim to evaluate the etiology and diagnostic procedures of this disorder on the basis of our own experience. METHODS: We saw four children aged 3 2/12 to 11 4/12 years with a cerebral infarction at our hospital. Three children were followed up until 6 months after the infarction. The case reports are presented. On the background of the literature, the etiology and diagnostic possibilities and requirements are discussed. RESULTS: As the underlying cause, we saw a hemolytic-uremic syndrome in one case, and a (post )infectious vasculitis following measles resp. scarlet fever in two cases. CCT, NMR, and transcranial Doppler sonography are the diagnostic methods of choice, although none of these by itself is able to diagnose this disorder with any certainty. Therapeutic measures are restricted to the causative disease. The prognosis is good quoad vitam, although serious regarding neurologic sequelae. CONCLUSIONS: An early diagnosis of this disorder is essential, because the only known effective therapy is the management of a possibly underlying disorder. Intensive physiotherapy as an additional measure is helpful to avoid neurological sequelae. PMID- 1501616 TI - [Mucoviscidosis screening with immunoreactive trypsin. Initial experiences in Austria]. AB - Up to now, 16.338 IRT-measurements have been carried out on dried blood spot specimens; 15.505 of them were taken in the first week of life. Related to a provisionally chosen cut-off point of 750 ng/ml, 134 newborns (= 0.86%) showed an elevated IRT-value and subsequently were recalled between the fourth and sixth week of life for a second IRT-determination. Twenty-five out of 116 reinvestigated children again showed an elevated value, as based on likewise provisional, age-dependent reference values. Four of these children subsequently were identified as CF patients by sweat testing. So far, we did not encounter any false-negative IRT values. We also commenced to establish a profile of reference values for the first twelve weeks of life; as yet, there are not enough data for definitely defining these limits of normality. In conclusion, IRT-screening appears to be a reliable method for identifying CF patients in the newborn period. Our preliminary results indicate an incidence of CF of 1 to 3880 in the southeast of Austria. PMID- 1501617 TI - [Taurine requirement of premature infants in parenteral nutrition]. AB - The aim of our studies was to clarify, which dose of taurine should be added to amino acid solutions, in order to achieve plasma levels in premature infants as they are found during nutrition with mother's milk. In 22 premature infants born in the 30th-35th week of gestation plasma taurine levels during parenteral nutrition were measured on the 5th-9th day of life before and after infusing an amino acid solution supplemented with taurine. For analysis the principle of chromatographical ion exchange was applied. The requirement of taurine was calculated by means of a linear regression between supply and blood level. The mean plasma taurine levels before substitution were 88.7 mumol (95%-range of tolerance: 32.8-240 mumol/l). In premature infants with cerebral haemorrhages significantly higher plasma taurine levels were observed. Continuous parenteral taurine supply of approximately 0.05 g/kg/day was able to raise the taurine level by about 70 mumol/l, which caused a plasma taurine level of above 100 mumol/l in any case. During parenteral nutrition it is possible to achieve taurine levels as high as in breastfed neonates by substituting taurine at an amount of 0.05 g taurine per kg body weight. PMID- 1501618 TI - [Extrahepatic bile duct atresia. Comparison of surgical and non-surgical therapy]. AB - In recent years hepatoportoenterostomy according to Kasai undoubtedly was the only successful therapy for extrahepatic biliary atresia. Since liver transplantation becomes more successful than previously, the question arises if the Kasai procedure is still justified. From this point of view a prospective study was started based on the following findings in 15 EHBA-children after hepatoportoenterostomy compared to those in 15 patients without the Kasai procedure: the survival rate at the end of two years of life; the development of ascites until the end of the first year of life; the weight and length percentiles at the end of the first year of life; and the activity of serum cholinesterase. In order to calculate significant differences in weight and length percentiles, the exact Fisher test was used. Serum cholinesterase activities of both the above mentioned groups were compared with each other, as well as with the normal values of a third group of 50 healthy children, by analyzing variances and then comparing one by one with adjustment for multiple comparisons. There was a significant difference between the operated and not operated group, and in addition between the non-operated and the healthy group. In contrast, no significant difference was detected between the operated and the healthy group. These differences were best demonstrated by the findings of weight and length percentiles and the activity of serum cholinesterase. From this we conclude sofar hepatoportoenterostomy undoubtedly is standard procedure in the treatment of EHGA. However, if the Kasai procedure fails or the liver disease progresses to a greater extent, liver transplantation will become the method of choice. PMID- 1501619 TI - [Acute diarrheal diseases. Treatment with carrot-rice viscous solution is more effective than ORS solution]. AB - In infants and children, the treatment of acute diarrhoea with glucose-based electrolyte solutions results in rehydration but does not reduce the severity and duration of diarrhoea. In german-speaking countries, rice- and carrot-based solutions have a long tradition in the treatment of diarrhoea and may also reduce stool output and the duration of diarrhoea. Therefore, we evaluated the efficacy and safety of a carrot-rice-based rehydration solution (Na 57 mmol/L, n = 70) and two conventional glucose-based solutions with high or low sodium concentrations (Na 90 mmol/L, n = 48 or Na 55 mmol/L, n = 60) in a prospective study. The study subjects were Pakistani boys and girls between 3 and 48 months of age with mild or moderate dehydration. We measured duration of diarrhoea, fecal and urine output, fluid intake and serum electrolytes. The duration of diarrhoea was significantly lower (p less than 0.05) in the group receiving the carrot-rice based rehydration solution (59.5 +/- 30.9 h) than in the groups receiving the high-Na (75.5 +/- 30.5) and low-Na (74.8 +/- 32.5) glucose-electrolyte solutions. The mean fecal output (p less than 0.01) and fluid intake (p less than 0.001) were also significantly lower in the infants and children receiving the carrot rice-based rehydration solution. No major electrolyte imbalances were observed in the three groups. We conclude that the carrot-rice-based rehydration solution was safe and more effective than two conventional glucose-electrolyte solutions in the rehydration of infants and children with acute diarrhoea. PMID- 1501620 TI - AAEM case report #24: electrodiagnosis in posttraumatic syringomyelia. AB - An adult male with C-7 quadriplegia developed neck pain. Axillary F central latencies were prolonged, and MRI showed a syrinx extending to C-1. After shunting, F latencies normalized. At subsequent follow-up, a rostral syrinx persisted by magnetic resonance imaging (MRI); motor evoked potential (MEP) latencies were prolonged but F latencies were normal. Later, the syrinx was less distended by MRI, MEPs normalized, and strength improved. We discuss the electrophysiologic methods available for diagnosing and monitoring posttraumatic syringomyelia. PMID- 1501621 TI - Insulin increases amino acid transport into rat soleus motor axons. AB - Hyperosmotic neurosecretion was used to measure basal and insulin-stimulated amino acid and myoinosital transport into rat motor nerve terminals. L-Alanine and alpha(methylamino)-isobutyric acid (a nonmetabolizable system A-specific analog) transport was rapid into motor nerve terminals innervating a fast-twitch muscle, the extensor digitorum longus, and slow into motor nerve terminals innervating the soleus, a slow-twitch muscle. A physiological concentration of insulin, 10 microU/mL, increased L-alanine and alpha(methylamino)-isobutyric acid transport into motor nerve terminals in the soleus. Large doses of insulin, 100 or 1000 microU/mL, had no effect on L-alanine or alpha(methylamino)-isobutyric acid transport into nerve terminals in the extensor digitorum longus. There was negligible basal or insulin-stimulated transport of D-alanine or myoinositol into nerve terminals of the soleus or extensor digitorum longus. These studies show that insulin regulates sterospecific amino acid transport into soleus motor axons, but has no effect on the rapid amino acid transport into extensor digitorum longus motor axons. Differences in basal and insulin-stimulated transport suggest that motor axons differ in their metabolism, and might be selectively vulnerable to disease processes. PMID- 1501622 TI - Improved medium with EGF and BSA for differentiated human skeletal muscle cells. AB - Epidermal growth factor (EGF) and bovine serum albumin (BSA) are both required for serum-free clonal growth of human muscle satellite cells (HMSC). However, neither inhibits differentiation of HMSC, and when both are added to a minimal serum-free differentiation medium, they enhance survival and maintenance of human myotubes. A combination of 10 ng/mL EGF and 0.5 mg/mL BSA, added to MCDB 120 plus 10 micrograms/mL insulin, increases both total protein per dish and total creatine kinase activity, and keeps the myotubes in good condition for a longer period of time. The myotubes become cross-striated and exhibit frequent spontaneous twitching. Substantial amounts of neonatal myosin heavy chain and the MM isozyme of creatine kinase are expressed, together with detectable amounts of adult fast myosin heavy chain. With regular feeding, these cultures can be maintained for at least 3 weeks with no overgrowth by mononucleate cells, and with far less degeneration than with insulin as the only supplement. PMID- 1501623 TI - Myotrophic effects of an anabolic steroid in rabbit limb muscles. AB - There has been no reliable evidence that the actions of anabolic steroids extend to limb muscles. In this study, female rabbits were treated with anabolic steroid (nandrolone decanoate) or arachis oil placebo for 4 weeks or 12 weeks. After 12 weeks, tibialis anterior muscles of treated animals showed highly significant increases in wet weight (38%), twitch tension (66%), maximum isometric tetanic tension (48%), maximum cross-sectional area (27%), and specific tension (17%). Fiber type composition showed a significant trend toward a less oxidative metabolic character. The experiments provided clear physiological and morphological evidence of a steroid-induced hypertrophy that was not attributable to fluid retention or changes in body weight. Of the muscles examined, the myotrophic effect was confined to the tibialis anterior muscle; extensor digitorum longus, plantaris, and soleus muscles showed no significant response. The work establishes an experimental model for the responses of limb muscles to anabolic compounds. PMID- 1501624 TI - The influence of the stimulus on normal sural nerve conduction velocity: a study of the latency of activation. AB - Conduction along the sural nerve was studied in 64 normal subjects using near nerve electrodes. Conduction velocities over the same nerve segments were calculated: (1) from the latency recorded from a site of stimulation to a site of recording (1R-method); and (2) from the difference in latency between 2 recording sites, the site of stimulation being situated elsewhere along the nerve (2R method). Consistently faster velocities were seen with the 2R-method and could best be explained by a fixed delay of about 0.15 ms at the stimulus site (latency of activation, utilization time). This delay was markedly prolonged when a ramp rather than a rectangular stimulus was applied, though fast fibers were excited with both types of stimuli. The delay is thought to be dependent on the relationship between the density of current at the stimulus site and the threshold of responding fibers. PMID- 1501627 TI - Twitch and tetanus in mdx mouse muscle. AB - We compared mdx and C57BL10 anterior tibial muscle force in situ (single pulse, multiple pulse, staircase, posttetanic potentiation, and fatiguing stimulation patterns) to define muscle strength, physiology, and fatigue resistance. The relatively hypertrophied mdx muscle showed: reduced strength (N/cm2), an increased twitch-tetanus ratio, and resistance to post-fatigue twitch slowing. These differences implicate altered mdx calcium regulation, and emphasize the importance of measuring both muscle function and morphology in mdx treatment trials. PMID- 1501625 TI - McArdle's disease and gout. AB - We report the first case of McArdle's disease (muscle phosphorylase deficiency) and tophaceous gout. To examine the contribution of adenine nucleotide degradation to the disturbance of uric acid metabolism, we labeled the adenine nucleotide pool with [8-14C]adenine, and measured plasma and urine purines following vigorous exercise tests. Plasma and urinary hypoxanthine and xanthine concentrations and the specific radioactivity of urinary purines increased markedly, but plasma urate levels and uric acid excretion were not substantially modified. We suggest that, in this patient, the association of McArcle's disease with gout is coincidental. PMID- 1501626 TI - Transcranial magnetic stimulation of the facial nerve: intraoperative study on the effect of stimulus parameters on the excitation site in man. AB - Magnetic stimulation (magStim) of the intracranial facial nerve is performed in clinical and research settings, but the activation site is a matter of controversy. Latencies of nasalis muscle responses to magStim were, therefore, compared with those obtained by direct electrical stimulation of the facial nerve (a) at the root exit zone (REZ); (b) at the porus of the facial canal; and (c) in the stylomastoid fossa during microvascular decompression operations in the cerebellopontine angle (CPA). Measurements of latencies of the nasalis muscle response, obtained while the stimulating coil was placed over the parieto occipital area of the scalp, indicated that it was the labryinthine segment of the facial canal, 5 to 16 mm distal to the CPA, that was activated. This would be in agreement with studies of physical models reported in the literature that showed (a) the strength of the electrical current generated by a magnetic field is particularly high close to a nerve foramen; and (b) excitation to magStim is most likely to occur where the induced electrical field changes rapidly over distance, i.e., at anatomical boundaries between media of high and low specific resistance. These characteristics are found at the end of the labyrinthine segment of the facial canal, where the facial nerve leaves the low-resistance cerebrospinal fluid and enters the high-resistance petrous bone. The site of neural excitation is robust and unaffected by stimulus intensity and current direction within a wide range, or by large changes in location of the coil.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1501628 TI - Case-of-the-month: painful thigh mass in a young woman: diabetic muscle infarction. AB - A 29-year-old female with type I diabetes mellitus developed pain, focal tenderness, and swelling in the posterior left thigh. Subsequent evaluation included a muscle biopsy, which revealed large confluent areas of necrosis and edema, compatible with a diagnosis of diabetic muscle infarction (DMI). Diabetic muscle infarction (DMI) is an unusual neuromuscular complication of diabetes mellitus. DMI begins with the acute onset of focal pain and swelling in the thigh. The anterior compartment (quadriceps muscle group) or posterior compartment (hamstring muscle group) are most frequently involved. The focal region of muscle damage can be noninvasively viewed by magnetic resonance imaging and radionuclide scans. Muscle biopsy demonstrates large confluent regions of muscle necrosis and edema. DMI needs to be differentiated from other processes that can cause leg pain in a diabetic patient. PMID- 1501629 TI - The HIV wasting syndrome. PMID- 1501630 TI - Mimicry of elastin repetitive motifs by Theileria annulata sporozoite surface antigen. AB - Theileria annulata is an important pathogen of cattle in the tropics. The gene sequence of a sporozoite surface antigen (SPAG-1) is reported. Data is also presented demonstrating that SPAG-1 is synthesised as a large precursor. This antigen, which is a candidate for inclusion in a subunit vaccine, shows a remarkable degree of molecular mimicry to the extracellular matrix protein elastin. It contains both repetitive motifs PGVGV and VGVAPG. Immunofluorescence using a monoclonal antibody against VGVAPG confirmed that this peptide is expressed on sporozoites as predicted. The presence of VGVAPG is particularly interesting since this is the ligand for elastin receptors on a range of cell types, including macrophages/monocytes which are a major class of host target cells. It is proposed that this antigen represents the ligand whereby T. annulata recognises its host cells. PMID- 1501631 TI - Leishmania tarentolae taxonomic relatedness inferred from phylogenetic analysis of the small subunit ribosomal RNA gene. AB - The sequence of the Leishmania tarentolae SSU rRNA (small subunit or 18S rRNA) gene was completely determined from 2 different strains and used to determine phylogenetic relationships between this organism and other trypanosomatids. Extensive structural similarities were observed between L. tarentolae and mammalian leishmanias the SSU rRNA. Phylogenetic reconstructions, using distance matrix or parsimony methods, showed large evolutionary distances between trypanosomes, either African and American, and L. tarentolae. Further analysis using intergenic rDNA spacer (IGS) sequences as probes in dot blot experiments confirmed the results obtained with the SSU rDNA comparisons. The data presented here clearly indicate that L. tarentolae is closely related to the mammalian parasite Leishmania donovani and highly divergent from trypanosomes. PMID- 1501632 TI - Random mating of natural Plasmodium populations demonstrated from individual oocysts. AB - DNA amplified from individual Plasmodium vivax oocysts, produced by feeding mosquitoes directly on naturally infected humans in Thailand, was used to study cross-mating of 2 polymorphs of the circumsporozoite (CS) gene, VK 210 and VK 247. Alleles were detected in matched blood parasites, sporozoites, and individual oocysts with oligoprobes specific to characteristic repeat units. Oocysts developing from 3 cases in which mixed alleles were present in the blood parasites had genotype frequencies, including hybrids, consistent with the Hardy Weinberg equilibrium. There was apparently no barrier to hybridization of the 2 alleles nor a bias, as has been found in some laboratory experiments, favoring hybrid formation. These are the first measurements of cross-mating frequencies directly from natural Plasmodium infections and the first observations of genetic hybridization in P. vivax. PMID- 1501633 TI - Mechanisms of microenvironmental pH regulation in the cuticle of Ascaris suum. AB - The excretion kinetics of various organic acids by Ascaris suum were quantified to determine if the excretion of these metabolic end-products could generate and maintain a microclimate pH within the aqueous compartment of the cuticle. Ligated and nonligated A. suum were incubated in media buffered with 0.25 or 2.5 mM Hepes (initial pH 7.5) or 0.5 or 5 mM glycine (initial pH 3.25). The concentration of organic acids and the pH of the media were followed for 24 h. Several volatile fatty acids, including acetic, 2-methylbutyric, 2-methylvaleric, n-valeric, and n butyric, were excreted at relatively high rates. Propionic, n-caproic, 2 methylcaproic, tiglic acid, and the non-volatile organic acids, lactic and succinic, were excreted more slowly. The organic acids were excreted at a constant rate and in apparently fixed molar concentration ratios. The accumulation of organic acids was associated with changes in pH of the medium until a limiting constant pH, in the vicinity of the pKa of the volatile fatty acids, was reached. The rate of organic acid excretion was not affected by initial medium pH, buffer capacity, or parasite ligation. The rate of pH change induced by the excretion of organic acids was also insensitive to whether ligated or nonligated A. suum were used, but was dependent on the initial buffer capacity of the medium. These results suggest that A. suum excrete the end-products of carbohydrate metabolism across the cuticle. The presence of organic acids in the aqueous pores of the cuticle creates and maintains a microclimate pH of about 5.0 +/- 0.3. This pH will influence the transport properties of weak acids and bases and should be considered in the design of delivery systems for anthelmintics. PMID- 1501634 TI - Isolation, sequence and differential expression of the p58 gene family of Babesia bigemina. AB - Four copies of the gene encoding the merozoite surface protein p58 from the protozoan hemoparasite Babesia bigemina were amplified from genomic DNA by polymerase chain reaction (PCR) techniques, molecularly cloned and subjected to DNA sequence analysis. The amplified DNA (Bbg7, Bbg9, Bbg13, Bbg14) could be placed into 2 classes with respect to its size and the length of the open reading frame (ORF). With the exception of a single base substitution, the sequence of Bbg13 is identical to the cDNA sequence published earlier [1]. The Bbg7 and Bbg14 copies of p58 diverged from Bbg13 sequence at regions towards the 3' and 5' ends, respectively. In contrast, Bbg9 has incorporated both regions of divergence within its sequence. Using a cloned strain of B. bigemina, RNA-PCR and Northern blot analyses demonstrate the in vivo transcription of 3 of the 4 copies, although one of the 3 expressed copies is present in very low abundance. The relative abundance and size of the two p58 mRNA species detected are consistent with the 58- and 55-kDa proteins detected by in vitro translation of B. bigemina poly(A)+ mRNA by immunoprecipitation with an anti-p58 monospecific antibodies. These results indicate that the gene encoding p58 exists as a multigene family that appears to be differentially expressed in the blood stage of the parasite's life cycle. PMID- 1501635 TI - Cloning and expression in Escherichia coli of cDNAs encoding a 31-kilodalton surface antigen of Sarcocystis muris. AB - Using polyadenylated RNA isolated from Sarcocystis muris cyst merozoites, we have constructed a cDNA library in the expression vector lambda ZAP. Immunoscreening with monoclonal and polyclonal antibodies directed against a 31-kDa surface antigen of S. muris [1] yielded a number of clones with insert sizes ranging between 1.1 kb and 1.3 kb. An additional clone with an insert length of 1.55 kb was isolated by screening with a labeled DNA probe derived from one of the cDNA clones. The cDNA sequence was found to contain an open reading frame specifying a polypeptide of 280 amino acids with a predicted size of 29.7 kDa. The deduced amino acid sequence is rich in serine and threonine (22%) and harbors a hypothetical N-terminal signal peptide sequence as well as a C-terminal glycosyl phosphatidylinositol anchor attachment site. The predicted amino acid sequence has been confirmed by peptide sequencing and an analysis of the overall amino acid composition of the 31-kDa protein. A recombinant protein was obtained which was recognized by the polyclonal antibodies directed against the 31-kDa antigen. Antiserum raised against the purified fusion protein specifically reacted with a 31-kDa protein from S. muris cystozoites. Southern blot analysis indicated that the corresponding gene exists as a single copy within the S. muris genome. PMID- 1501637 TI - Alternative splicing of the Schistosoma mansoni gene encoding a homologue of epidermal growth factor receptor. AB - The complete coding DNA for a Schistosoma mansoni homologue of the epidermal growth factor receptor (SER) was characterized from cDNA clones obtained by homology to the tyrosine kinase domain of erbB. The DNA sequence predicts a 200 kDa translation product that contains a secretory leader, a cysteine-rich extracellular domain, a hydrophobic transmembrane sequence, and an intracellular tyrosine kinase domain. The SER transcript is present in cercariae and adult schistosomes. In addition to SER transcripts, schistosomes produce at least 3 variant transcripts encoding truncated SER products that include the secretory leader and a small portion of the extracellular domain followed by short sequences of unrelated, C-terminal amino acids. Based on these sequences, 2 of the variant mRNAs (class 2 and 5) appear to encode soluble, secreted proteins while one (class 4) encodes an SER variant protein with a hydrophobic C-terminus that may serve as a membrane anchor. Class 2 SER variant transcripts are present at levels comparable to SER transcripts in adult worms but are not detected in cercariae. Class 4 and 5 SER variant transcripts are also found within adult worms but at lower levels. Genomic cloning and characterization demonstrate that the variant SER transcripts arise through alternative splicing of the SER gene. PMID- 1501636 TI - Cloning of the gene encoding Leishmania donovani S-adenosylhomocysteine hydrolase, a potential target for antiparasitic chemotherapy. AB - A full-length gene encoding the S-adenosylhomocysteine hydrolase (AdoHcyase) enzyme has been isolated from a genomic library of Leishmania donovani DNA in lambda GEM-11 by cross-hybridization to the full-length human AdoHcyase cDNA. The nucleotide sequence of the SalI fragment contained a single open reading frame that encoded a polypeptide of 438 amino acids (47,712 Da). After maximum gap alignment, the predicted amino acid sequence of the leishmanial AdoHcyase was 70 73% identical to AdoHCyases from higher eukaryotes. In addition, a data base search revealed that the primary structure of all AdoHcyase proteins was highly homologous to that of a protein encoded by a mRNA from Drosophila melanogaster that maps near the r element function of the Abd-b homeotic gene. In Northern blots, the SalI fragment hybridized to a 3.0-kb transcript that presumably encodes the parasite enzyme. Southern blot analysis of genomic DNA revealed that the AdoHcyase gene did not exist as a tandemly repeated array within the L. donovani genome. Moreover, monoclonal antibodies generated against human AdoHcyase recognized a leishmanial protein on immunoblots. Finally, the growth of L. donovani promastigotes could be arrested by micromolar concentrations of 3 deazaaristeromycin (C3Ari) and 9-(trans-2',trans-3' dihydroxycyclopentanyl)adenine, 2 known inhibitors of mammalian AdoHcyase. C3Ari also induced a substantial expansion of the intracellular pools of both AdoHcy and S-adenosylmethionine (AdoMet), as well as a significant diminution of the AdoMet/AdoHcy ratio. Thus, AdoHcyase may have therapeutic potential for the selective treatment of diseases of parasitic origin. PMID- 1501638 TI - Brefeldin A inhibits protein secretion and parasite maturation in the ring stage of Plasmodium falciparum. AB - The release of all newly synthesized soluble proteins from the ring stage of Plasmodium falciparum-infected erythrocytes was reversibly blocked by brefeldin A, indicating the presence of a conserved step of classical eukaryotic secretory export within the parasite. This implies that proteins exported to the erythrocyte cytosol undergo secretory release at the parasite plasma membrane and subsequent translocation across the vacuolar membrane. Along with inhibiting protein export brefeldin arrested parasite maturation, but the cells remained viable even after 24 h in the presence of the drug. The results suggest that secretory export may be important for development, but not for immediate survival, at the ring stage. PMID- 1501639 TI - Utilization of a carbohydrate reserve comprised primarily of mannose by Leishmania donovani. AB - Promastigotes from late log phase and 3-day stationary phase cultures of Leishmania donovani were collected, washed in buffer, and the cell pellet was treated with boiling KOH. A putative carbohydrate storage material was then precipitated and washed in ethanol/LiBr. This material did not liberate glucose when treated with amyloglucosidase, indicating that it was not glycogen. Acid hydrolysis released a hexose which was identified as mannose by several criteria. Considerably more of this mannan-like carbohydrate is present in cells from 3-day stationary phase than from late log phase cultures, consistent with the ability of 3-day stationary phase cells to survive in non-nutrient buffer and maintain oxygen consumption for longer than log phase cells. The amount of this mannan like compound decreased by over 50% during a 3-h incubation in buffer of cells from 3-day stationary phase cultures. The presence of glucose during the incubation prevented the utilization of this carbohydrate, consistent with the possibility that it serves as an energy reserve. PMID- 1501640 TI - Regulation of hsp70 expression in Trypanosoma cruzi by temperature and growth phase. AB - The steady-state level of the hsp70 mRNAs of Trypanosoma cruzi cultured at different temperatures and growth conditions has been analyzed by Northern blotting. We show that only one size class of hsp70 mRNA, of about 2.2 kb, is transcribed from the hsp70 cluster and that its transcription is constitutive at 28 degrees C. However, after a heat shock treatment at 37 degrees C for 2 h of logarithmically growing parasites, the abundance of the hsp70 mRNA increased about 4-fold. A similar increase was observed at 28 degrees C when the parasite culture reached the stationary phase of growth. On the other hand, a heat shock at 42 degrees C did not change the steady state level of the 2.2-kb size class of hsp70 mRNA. However, accumulation of transcripts of high molecular weight was detected when stationary growing parasites were cultured at 42 degrees C for 2 h. Also at 37 degrees C the steady state level of the alpha- and beta-tubulin mRNAs of logarithmically growing parasites exhibited a slight increase but only after a period of 24 h. Analysis by one-dimensional immunoblots of the Hsp70 levels showed that at 37 degrees C the abundance of the protein was 4-fold higher than at 28 degrees C. Immunoblots of high-resolution two-dimensional gel electrophoresis showed, moreover, that various isoforms of this protein are constitutively expressed at 28 degrees C and that some of them have a specific pattern of induction at 37 degrees C. We observed, moreover, that the heat shock induces the expression of a series of proteins while it causes repression of others. PMID- 1501641 TI - Characterisation of melarsen-resistant Trypanosoma brucei brucei with respect to cross-resistance to other drugs and trypanothione metabolism. AB - An arsenical resistant cloned line of Trypanosoma brucei brucei was derived from a parent sensitive clone by repeated selection in vivo with the pentavalent melaminophenyl arsenical, sodium melarsen. The melarsen-resistant line was tested in vivo in mice against a range of trypanocidal compounds and found to be cross resistant to the trivalent arsenicals, melarsen oxide, melarsoprol and trimelarsen (33, 67 and 122-fold, respectively). A similar pattern of cross resistance was found in vitro using a spectrophotometric lysis assay (greater than 200-fold resistance to melarsen oxide and greater than 20-fold resistance to both trimelarsen and melarsoprol). Both lines were equally sensitive to lysis by the lipophilic analogue phenylarsine oxide in vitro, suggesting that the melamine moiety is involved in the resistance mechanism. Although trypanothione has been reported to be the primary target for trivalent arsenical drugs [1], levels of trypanothione and glutathione were not significantly different between the resistant and sensitive lines. Statistically significant differences were found in the levels of trypanothione reductase (50% lower in the resistant clone) and dihydrolipoamide dehydrogenase (38% higher in the resistant clone). However, the Km for trypanothione disulphide, the Ki for the competitive inhibitor Mel T (the melarsen oxide adduct with trypanothione) and the pseudo-first order inactivation rates with melarsen oxide were the same for trypanothione reductase purified from both clones. The melarsen-resistant line also showed varying degrees of cross resistance to the diamidines: stilbamidine (38-fold), berenil (31.5-fold), propamidine (5.7-fold) and pentamidine (1.5-fold). Cross-resistance correlates with the maximum interatomic distance between the amidine groups of these drugs and suggests that the diamidines and melaminophenyl arsenicals are recognised by the same transport system. PMID- 1501642 TI - The interaction of arsenical drugs with dihydrolipoamide and dihydrolipoamide dehydrogenase from arsenical resistant and sensitive strains of Trypanosoma brucei brucei. AB - D,L-dihydrolipoamide and D,L-dihydrolipoic acid react to form stable complexes with melarsen oxide with association constants of 5.47 x 10(9) and 4.51 x 10(9) M 1, respectively. These complexes possess 6-membered cyclic dithioarsenite rings which are 10-fold less stable than the 5-membered rings found in the trypanocidal drugs melarsoprol and trimelarsen, but 500-fold more stable than the 25-membered macrocyclic ring formed between melarsen oxide and dihydrotrypanothione. L-Lipoic acid concentrations in arsenical sensitive and resistant cloned lines of Trypanosoma brucei brucei have been determined by bioassay using a mutant of Escherichia coli auxotrophic for lipoate. The arsenical resistant strain was found to contain significantly less lipoic acid than the sensitive strain (19.2 +/- 4.3 and 9.7 +/- 2.9 pmol (10(8) cells)-1, respectively). The activity of the plasma membrane-associated dihydrolipoamide dehydrogenase was found to be slightly, but significantly increased in the arsenical resistant strain (34.7 +/- 1.4 and 47.8 +/- 3.7 mU mg-1, respectively). However, the Km for dihydrolipoamide and the inactivation kinetics with melarsen oxide were not significantly different between these strains. Estimates of the ratio of substrate to enzyme are of the order of 12:1 and 6:1 for arsenical sensitive and resistant strains, respectively, suggesting that these components are likely to be intimately associated with each other in the plasma membrane. These findings implicate lipoic acid, but not dihydrolipoamide dehydrogenase, in resistance to arsenical drugs, either through the mechanism of uptake or as the final target of these drugs. PMID- 1501643 TI - Rapid and simple method for isolating malaria DNA from fingerprick samples of blood. PMID- 1501644 TI - Characterization of the gene encoding sporozoite surface protein 2, a protective Plasmodium yoelii sporozoite antigen. AB - Sporozoite surface protein 2 (SSP2) is a 140-kDa, protective sporozoite surface protein from Plasmodium yoelii distinct from the circumsporozoite protein (CSP). A genomic clone containing the SSP2 gene was isolated and sequenced to determine its size, structural organization and deduced primary amino acid sequence. The coding sequence consists of a single, long open reading frame encoding 826 amino acids. The overall structure of SSP2 is similar to that of the CSP, consisting of a central region of immunogenic amino acid repeats flanked by non-repetitive sequence. SSP2 has one copy of a thrombospondin repeat motif in common with several cell adhesion molecules as well as with the CSP and the thrombospondin related anonymous protein (TRAP) of P. falciparum. Additionally, SSP2 shares substantial sequence similarity to TRAP, suggesting that TRAP is the analogue of SSP2 in P. falciparum. PMID- 1501645 TI - DNA fingerprints: a tool for identification and determination of the relationships between species and strains of Leishmania. AB - Using nonradioactive hybridization, the multilocal probes 33.15, F10 and (CAC)5 were shown to recognize multiple minisatellite regions in nuclear DNA of Leishmania, producing on Southern blots complex banding patterns typical of DNA fingerprints. We used the 33.15 probe to study 14 different strains belonging to 6 different species from both the sub-genus Viannia and the Leishmania mexicana complex of the sub-genus Leishmania. Distinct DNA fingerprints were obtained for each strain, permitting their identification. On the other hand, each strain showed little or no clonal variation. The information from the fingerprinting maps could be used for constructing phenograms and cladograms of the species and strains of Leishmania. PMID- 1501646 TI - Sulfate metabolism in Entamoeba histolytica. AB - Sulfate fluxes and sulfate metabolites in Entamoeba histolytica were characterized employing [35S]sulfate as a marker. Sulfate was taken up both across the plasma membrane and by pinocytosis; in growth medium (sulfate concentration, 1.1 mM) total uptake was 1.5 mumol h-1 (5 x 10(7) cells)-1. The fate of sulfate within the cells was investigated by thin-layer chromatography. Major metabolites (together greater than 3 mumol (5 x 10(7) cells)-1) were monoethyl sulfate and 3-cholesteryl sulfate; both these products were released into the growth medium. As minor components we identified the activated sulfate derivatives, adenosine-5'-phosphosulfate and 3'-phosphoadenosine-5' phosphosulfate. In addition, up to 10% of the sulfate taken up was incorporated into high-molecular weight material (possibly proteoglycans). We propose that sulfurylation of cholesterol may play a role in controlling membrane sterol content. PMID- 1501647 TI - Characterisation of the secretory acetylcholinesterases from adult Nippostrongylus brasiliensis. AB - The biochemical nature and relationship between the different isoforms of acetylcholinesterase (AChEs) secreted by adult Nippostrongylus brasiliensis was investigated, primarily via staining for enzyme activity and active-site labelling with [3H]-diisopropylfluorophosphate (DFP). Analysis by 1-dimensional SDS-PAGE under non-reducing conditions revealed the existence of 2 proteins of 74 kDa and 39-kDa, and each protein resolved as 2 species by isoelectric focusing. Both AChEs were co-purified via affinity chromatography on 9-[N beta-(epsilon aminocaproyl)-beta-aminopropylamino]-acridine-coupled Sepharose 6B, and utilised to raise a polyclonal rabbit antiserum. Examination of the expression of secretory AChEs by adult worms during their residence in the gastrointestinal tract showed that the initial secretion of both forms on day 4 post-infection switched to predominant secretion of the 39-kDa protein by day 8. Immunoprecipitation of 35S-labelled products of in vitro translation via RNA from day 4 and day 8 worms predicted a single primary translation product of 59 kDa. These data suggested that the 'switching' event seen in vivo most likely corresponded to processing of the 74-kDa molecule. This interpretation was supported by limited digestion with V8 protease and chymotrypsin, which showed that the 74-kDa and the 39-kDa proteins possessed structural similarities. PMID- 1501648 TI - Intramolecular mapping of Plasmodium falciparum P126 proteolytic fragments by N terminal amino acid sequencing. AB - Protein P126 (also called P140, P113, SERA, SERP1) is a major parasitophorous vacuole antigen of Plasmodium falciparum. This protein is processed upon merozoite release into 2 fragments of 73 kDa (P73) and 50 kDa (P50), which are found in the culture medium. P73 is composed of 2 polypeptides of 47 and 18 kDa linked by disulfide bridges. In the presence of leupeptin, an inhibitor of serine and cysteine proteases which inhibits merozoite release, a 56-kDa intermediate product (P56) is recovered in the culture medium instead of P50. In order to map these proteolytic fragments on the 126-kDa precursor, we purified them from Plasmodium falciparum culture medium by immunoadsorption, SDS-electrophoresis and Western blotting on PVDF membrane and determined the N termini of P126, P73 (P47 and P18), P50 and P56. Comparison of these sequences with the amino acid sequence deduced from the P126 gene allowed the mapping of the different fragments on the precursor. P47 was at the N-terminal and P18 at the C-terminal end of P126. P56 and P50 had the same N-termini and were located in the middle of P126. This latter result indicates that the proteolysis of P56-P50 occurs at the C-terminus of P56. The peptide bonds cleaved by leupeptin-insensitive activities are Glu-Thr and Gln-Asp; C-terminal sequencing of P50 will be needed to identify the leupeptin-sensitive cleavage site. PMID- 1501649 TI - Arginine metabolism during culture of Giardia intestinalis. AB - The effect of arginine on the growth and metabolism of Giardia intestinalis trophozoites was determined. Supplementation of the normal growth medium (Diamond's TYI-S-33) with 5 or 10 mM arginine accelerated trophozoite growth over the first 2 days. There was a corresponding rapid utilisation of arginine, with none being detectable after this time. The decrease was associated with the appearance in the growth medium of 1 mol of ornithine and 2 mol of ammonia per mol of arginine utilised, the stoichiometry being consistent with the operation of the arginine dihydrolase pathway. Subsequently, there was a decrease in the ammonia concentration in the medium. Removal of arginine from the medium by pretreatment with arginase substantially decreased cell growth. In TYI-S-33 medium containing no added glucose, instead of the normal 50 mM glucose concentration, arginine supplementation also increased cell growth over the first 2 days, with concurrent stoichiometric production of ornithine and ammonia. However, in these conditions, the ammonia concentration remained elevated. This suggests that under normal conditions there is re-uptake of ammonia, which is glucose dependent. The observations confirm the operation of a functional arginine dihydrolase pathway in G. intestinalis. The concordance of cessation of rapid growth with the depletion of arginine, and the beneficial effect on growth of arginine supplementation suggests that arginine availability is a limiting factor during the initial stages of rapid growth. It would appear that arginine is a major potential energy source during the initial stages of giardial growth, and that supplementation of Diamond's TYI-S-33 medium with additional arginine may provide an improved in vitro culture medium. PMID- 1501650 TI - Gastrointestinal damage associated with the use of nonsteroidal antiinflammatory drugs. AB - BACKGROUND: Long-term use of nonsteroidal antiinflammatory drugs (NSAIDs) may lead to inflammation of the small intestine associated with occult blood and protein loss. The aim of this study was to investigate the prevalence and structural correlates of this enteropathy. METHODS: We examined the stomach, duodenum, and small intestine of 713 patients post mortem. Of these patients, 249 had had NSAIDs prescribed during the six months before death and 464 patients had not. All visible small intestinal lesions were removed for histologic examination, and specific etiologic factors were sought. The prevalence of nonspecific small-intestinal ulcers and ulcers of the stomach and duodenum was compared in the two groups of patients. RESULTS: Nonspecific small-intestinal ulceration was found in 21 (8.4 percent) of the users of NSAIDs and 3 (0.6 percent) of the nonusers (difference, 7.8 percent; 95 percent confidence interval, 5.0 to 10.6 percent; P less than 0.001). Three patients who were long term users of NSAIDs were found to have died of perforated nonspecific small intestinal ulcers. Ulcers of the stomach or duodenum were found in 54 (21.7 percent) of the patients who used these drugs and 57 (12.3 percent) of those who had not (difference, 9.4 percent; 95 percent confidence interval, 3.9 to 15.1 percent; P less than 0.001). CONCLUSIONS: Patients who take NSAIDs have an increased risk of nonspecific ulceration of the small-intestinal mucosa. These ulcers are less common than ulcers of the stomach or duodenum, but can lead to life-threatening complications. PMID- 1501651 TI - Role of plasminogen-activator inhibitor type 1 in the pathogenesis and outcome of the hemolytic uremic syndrome. AB - BACKGROUND: Deposition of fibrin in glomeruli and renal failure are characteristic features of the hemolytic uremic syndrome. An inhibitor of glomerular fibrinolysis has been detected in plasma from children with this disorder. In this study, we define the inhibitor and show that its plasma level is correlated with the outcome of the disease. METHODS AND RESULTS: Plasminogen activator inhibitor type 1 (PAI-1) in plasma was measured with an assay employing a specific monoclonal antibody in 40 consecutive children hospitalized with the hemolytic uremic syndrome: 12 who recovered adequate renal function (serum creatinine, less than or equal to 2.0 mg per deciliter [177 mumol per liter]) without dialysis, 23 who recovered adequate renal function after peritoneal dialysis, and 5 who did not recover adequate renal function after undergoing dialysis. At presentation, plasma PAI-1 levels were higher in the patients with the hemolytic uremic syndrome than in nine children with other forms of acute renal failure. That the inhibitor was PAI-1 was indicated by the fact that it was a potent inhibitor of tissue plasminogen activator, was acid-resistant, and was not inhibited by denaturation (all unique traits of PAI-1) and that it was neutralized by an antibody specific for PAI-1. Multivariate discriminant-function analysis revealed that the duration of elevated PAI-1 activity was strongly correlated with the outcome of the disease (P less than 0.001). Peritoneal dialysis reduced plasma PAI-1 levels dramatically. CONCLUSIONS: Our studies suggest that PAI-1 is the circulating inhibitor of fibrinolysis in the hemolytic uremic syndrome. Normalization of plasma PAI-1 levels (e.g., by peritoneal dialysis) is correlated with improvement in renal function. However, the possibility that increased plasma levels of PAI-1 are either causes or effects of the hemolytic uremic syndrome is not unequivocally established by these studies. PMID- 1501652 TI - Relation of skin capillary pressure in patients with insulin-dependent diabetes mellitus to complications and metabolic control. AB - BACKGROUND: Microvascular disease is a major problem in patients with diabetes mellitus. It has been suggested that diabetic microangiopathy may result from an increase in capillary blood flow and capillary hypertension, but direct evidence of capillary hypertension in such patients is lacking. METHODS: We measured capillary pressure at the summit of the capillary loop by direct microcannulation of skin nail-fold capillaries and a dynamic method of pressure measurement in 29 patients with insulin-dependent (Type I) diabetes and 29 normal subjects matched for age and sex. Among the diabetic patients, 7 had had diabetes for less than one year, 12 had incipient nephropathy (albumin excretion, 20 to 200 micrograms per minute), and 10 had overt nephropathy (albumin excretion, greater than 200 micrograms per minute). In addition, seven patients with no evidence of nephropathy were studied before and after three months of improved glycemic control. RESULTS: The median capillary pressure in the diabetic patients was 20.4 mm Hg (range, 13.6 to 25.3), as compared with 16.7 mm Hg (range, 12.8 to 22.8; P less than 0.001) in the normal subjects. The values were higher in each subgroup of diabetic patients than in the corresponding group of normal subjects, but the values did not differ among the three subgroups of diabetic patients. In the seven patients who were studied before and after three months of improved glycemic control, the median capillary pressure fell from 20.0 mm Hg (range, 18.5 to 21.7) to 17.8 mm Hg (range, 14.1 to 20.3; P = 0.02). CONCLUSIONS: Nail-fold capillary hypertension may develop early in the course of diabetes, before the emergence of microvascular disease, and may be influenced by changes in metabolic control. PMID- 1501653 TI - Brief report: the hemodynamic mechanism of pounding in the neck in atrioventricular nodal reentrant tachycardia. PMID- 1501654 TI - Predisposing factors for severe, uncontrolled hypertension in an inner-city minority population. AB - BACKGROUND: Hypertensive emergency and urgent hypertension are the most severe forms of uncontrolled hypertension and are now seen predominantly in poor, minority populations. We studied the characteristics of the medical care received by patients with these conditions in order to identify risk factors for severe, uncontrolled hypertension. METHODS: Using a case-control study design, we interviewed 93 patients with severe, uncontrolled hypertension who presented in the hospital emergency room and 114 control patients with hypertension; both groups were seen at two New York City hospitals from 1989 through 1991. All the patients were black or Hispanic. Multiple logistic-regression models were used to adjust for age, sex, race or ethnic background, education, smoking status, alcohol-related problems, and use of illicit drugs during the previous year. RESULTS: After additional adjustment for lack of health insurance, severe, uncontrolled hypertension was found to be more common among patients who had no primary care physician (adjusted odds ratio, 3.5; 95 percent confidence interval, 1.6 to 7.7) and among those who did not comply with treatment for their hypertension (adjusted odds ratio, 1.9; 95 percent confidence interval, 1.4 to 2.5). Lack of health insurance was marginally associated with severe, uncontrolled hypertension (adjusted odds ratio, 1.9; 95 percent confidence interval, 0.8 to 4.6) after adjustment for lack of a primary care physician and noncompliance with antihypertensive treatment. Patients without a primary care physician and without health insurance were more likely to have their blood pressure checked and receive prescriptions for blood-pressure medications in emergency rooms than in physicians' offices or clinics. CONCLUSIONS: Characteristics of both the health care system and patients' behavior are associated with severe, uncontrolled hypertension. Improving access to primary care physicians, through health insurance or other means, may be an effective strategy for improving control of hypertension in disadvantaged minority populations. PMID- 1501655 TI - The presidential candidates and health care reform. PMID- 1501656 TI - The Bush administration's health care plan. PMID- 1501657 TI - The Clinton health care plan. PMID- 1501658 TI - Commentary: measuring the candidates on health care. PMID- 1501659 TI - Commentary: politics and the health care system. PMID- 1501660 TI - "Prolife" perinatologist. PMID- 1501661 TI - "Prolife" perinatologist. PMID- 1501662 TI - "Prolife" perinatologist. PMID- 1501663 TI - "Prolife" perinatologist. PMID- 1501665 TI - "Prolife" perinatologist. PMID- 1501664 TI - "Prolife" perinatologist. PMID- 1501666 TI - "Prolife" perinatologist. PMID- 1501667 TI - Early zidovudine and survival in HIV infection. PMID- 1501668 TI - Early zidovudine and survival in HIV infection. The Veterans Affairs AIDS Cooperative Studies Group. PMID- 1501669 TI - Intravenous immune globulin versus plasma exchange in Guillain-Barre syndrome. PMID- 1501670 TI - Intravenous immune globulin versus plasma exchange in Guillain-Barre syndrome. PMID- 1501671 TI - Management of acute hypercalcemia. PMID- 1501672 TI - Beware of offers of indemnity. PMID- 1501673 TI - Tinea gladiatorum. PMID- 1501674 TI - [Kinetics of thermal killing of microorganisms in egg yolk]. AB - Egg yolk is relating to its germ content and enzyme activity only restricted storable. Unpasteurized egg yolk get spoiled between a few hours and days. The rapid spoilage can be reduced by a pasteurization and following cold storage. The storage stability of egg yolk can be increased by additives, e.g. salt or saccharose. Kinetic results of the thermal microorganisms destruction in the egg yolk with and without stabilizing additives are presented in this article. It will be shown that the evaluation method from REICHART gives representative results for mixed cultures, too. A further evaluation method by a differential equation will be demonstrated and discussed. PMID- 1501675 TI - Toxicological evaluation of rapeseed products in a subacute feeding study in rats. AB - Groups of 15 male rats were fed ad libitum for 4 weeks standard diet containing 0, 2.5, 5 or 10% rapeseed protein isolate (RPI), 2.5, 5 or 10% rapeseed extraction residue (RER) or 10% casein. Body weight gain and food intake were recorded weekly. Clinical chemistry analyses, haematology, urinalysis, organ weights and histology were performed terminally. Serum alanine aminotransferase was decreased by RPI, RER and casein, while serum albumin only increased in rats fed RER. Microscopic examinations revealed abnormalities in liver and kidneys of animals at the 10% RPI, RER and casein levels. The absolute liver weights showed increases in the 5 and 10% RER groups and in the 10% RPI group. The relative kidney weights were reduced at all RER levels and in the 2.5% RPI group. Antithyroid activity of the rapeseed products were not noted. PMID- 1501676 TI - Study on some trace elements content of certain internal organs and muscles of lambs. AB - The aim of the investigations was the determination of the lead, cadmium, copper, zinc and iron content. It was found that lead and cadmium content in the kidneys and livers of lambs from the Sedziszow region was by several times higher than in the case of lambs from an agricultural region (control). The average lead concentration in 31% of kidneys and livers coming from the lambs of the Sedziszow region exceeded the permissible norm. PMID- 1501677 TI - [The effect of thyroid- and sex hormones on triglyceride secretion in rat liver]. AB - The influence of thyroxine, estradiol and testosterone on the triacylglycerol (TG) secretion rate out of the liver into the blood as well as on concentrations of FFA, triglycerides, and glucose in serum was determined. All of these experiments were carried out under different nutritional conditions (non-fasting, and 10 or 16 h fasting, respectively). Accordingly the results after hormone application were compared with three groups of controls. Within these control groups increasing time of fasting caused exclusively an enhancement of FFA concentrations, while the TG secretion rate and other parameters were not influenced. Concerning all hormones effects on several lipid parameters have been observed. In particular, a decrease of FFA concentrations in comparison with controls after 16 h fasting was evident. In these cases, the TG secretion rate and TG concentration in serum were simultaneously lowered. Both alterations may be a consequence of a diminished mobilization of FFA in adipose tissue. Increases of FFA concentrations in serum after hormone application, compared with the corresponding controls, only occurred after administration of thyroxine and testosterone, while changes of the TG secretion rate and the TG concentration in serum were scarcely observed. Final remarks about the actual influence of hormones on the investigated parameters, especially TG secretion rate were drawn including results of a previous paper, where catecholamines, insulin, and prednisolone had been tested under the same conditions. PMID- 1501678 TI - Time-intensity determination of bitterness. PMID- 1501679 TI - Bioavailability of drugs to the brain and the blood brain barrier. PMID- 1501680 TI - The blood-brain barrier is not a "barrier" for many drugs. PMID- 1501681 TI - Drug delivery to the brain: barrier modification and drug modification methodologies. PMID- 1501682 TI - Some relationships between addiction and drug delivery to the brain. AB - Hemodynamic radioisotope studies of brain blood flow in humans have been correlated with the delivery of some common addictive drugs. Both lipophilic and hydrophilic tracers were used in the hemodynamic studies. Iodoantipyrine is lipophilic and is completely cleared by brain during a single brain circulatory passage, as are cocaine and nicotine. Iodohippurate is hydrophilic, so its brain clearance after IV injection resembles that of morphine. The earlier studies performed in humans have been related here with recent studies of blood brain penetration of drugs of abuse. As presented, these separate studies are consistent with the proposed hypothesis that the interval between drug intake and perceived effect is a significant consideration when explaining severity of addiction. The shorter the time interval between drug intake and its perceived effect, the more severe the addiction appears to be. This relationship may explain differences in severity of addiction to the same drug taken by various routes of administration. PMID- 1501683 TI - Cultured brain microvessel endothelial cells as in vitro models of the blood brain barrier. PMID- 1501684 TI - Opioid peptide drug development: transport of opioid chimeric peptides through the blood-brain barrier. AB - The use of chimeric peptides and physiologic-based strategies for drug delivery through the BBB may be applied to opioid peptides (dynorphins, endorphin analogs, and enkephalin analogs), and these agents have considerable advantages in drug development with respect to drug addiction. Recent research has allowed for the development of efficacious BBB drug transport vectors, as well as the demonstration that these vectors allow for shuttling of opioid peptides through the BBB in vivo. The major challenge to future research is the development of coupling strategies that allow for the release of biologically active opioid peptide from the drug transport vector following its cleavage by disulfide reductase enzymes, which are abundant in brain. These coupling strategies must be developed in advance since the amino groups necessary for coupling are incorporated into the opioid peptide at the level of solid-state synthesis. PMID- 1501685 TI - Redox approaches to drug delivery to the central nervous system. PMID- 1501686 TI - Drug delivery to the brain using an anti-transferrin receptor antibody. PMID- 1501687 TI - Permeation of the blood-brain barrier for drug delivery to the brain. PMID- 1501688 TI - Pathways into, through, and around the fluid-brain barriers. AB - The potential intracellular and extracellular pathways that blood-borne substances may follow for circumventing the fluid-brain barriers and entry to the CNS are numerous. The extracellular avenues, patent to blood-borne protein the size of IgM, and movement of blood-borne macromolecules through perivascular clefts deep into the CNS complicate the interpretation and identification of bona fide transcytosis through the BBB. The often-stated belief in literature reviews of the BBB that nonfenestrated cerebral endothelia fail to engage in endocytosis and possess few vesicles under normal conditions is invalid. Endocytic vesicle formation and vesicular traffic among constituents of the endomembrane system are no different in BBB endothelia than in other cell types. Available biochemical and morphological data advocate the transcytosis of blood-borne protein and peptides through nonfenestrated cerebral endothelia. However, absence of demonstrable endocytic activity at the abluminal front compared with a very prominent endocytic activity at the luminal surface of BBB endothelia argues against bidirectional membrane trafficking through the BBB and supports the concept of a brain-blood barrier. The latter is no less significant functionally than the BBB and may be more so in deterring transendothelial transfer of peptides and proteins bidirectionally through the nonfenestrated cerebral endothelium. The difficulty in interpreting transcytosis through BBB endothelia is not encountered for epithelia of the blood-CSF barrier at the level of the choroid plexus. Choroid epithelia engage in endocytosis circumferentially; hence, the potential for transcytosis and circumvention of the blood-CSF barrier through an intraepithelial route exists bidirectionally in the choroid plexus. PMID- 1501689 TI - Neuroactive peptides and amino acids at the blood-brain barrier: possible implications for drug abuse. PMID- 1501690 TI - The basic neurobiology of addiction. AB - This overview on cocaine's addiction liability is presented in this monograph on the blood-brain barrier (BBB) because the National Institute on Drug Abuse has been given the task of finding pharmacotherapies to treat addiction. Knowledge about the BBB might help researchers design better drugs or approaches to keep the "good" drugs inside and/or the "bad" drugs outside. It is to be hoped that the BBB community can be convinced that drug abuse is an exciting area and that work on biological barriers has something to offer. PMID- 1501691 TI - MPTP toxicity and the "biochemical" blood-brain barrier. PMID- 1501692 TI - An overview of the multiple functions of the blood-brain barrier. AB - The BBB formed by brain capillary endothelial cells is now recognized as more than an impermeable wall. It has specific transport systems that facilitate the uptake of important nutrients and hormones and active pumps that help to regulate the concentrations of ions and metabolites in the brain's ISF. Enzymes present in the endothelial cell metabolize neurotransmitters, drugs, and toxins before they can enter the brain and disrupt its function. Many of these properties are likely to be under regulation either by neurotransmitters and hormones released in the brain or by those present in the systemic circulation. As a result of this constellation of diverse functions, the brain capillary endothelial cell is able to efficiently supply the brain with the metabolites that it requires while contributing to the maintenance of the brain's ionic homeostasis and protecting it from circulating toxins. PMID- 1501693 TI - Formation and differentiation of brain capillaries. PMID- 1501694 TI - Nonpermeable and permeable vessels of the brain. PMID- 1501695 TI - Human Frontiers in rough water. PMID- 1501696 TI - Conflict over scope of research splits Human Frontier programme. PMID- 1501697 TI - Report urges UK universities to recoup full overhead costs. PMID- 1501698 TI - Rifkin wins battle over NIH growth trials. PMID- 1501699 TI - Widespread CF testing inevitable, congressional report finds. PMID- 1501700 TI - Bush spins tall tale of technology transfer. PMID- 1501701 TI - Japan 'loses' new funds for research infrastructure. PMID- 1501702 TI - French increase ties with industry but researchers still face hurdles. PMID- 1501703 TI - Differences in brain size. PMID- 1501704 TI - Differences in brain size. PMID- 1501705 TI - Fetal tissue banks. PMID- 1501706 TI - Popovic says OSI is wrong. PMID- 1501707 TI - Orphan drugs. PMID- 1501708 TI - Tuberculosis. Back to a frightening future. PMID- 1501709 TI - Natural products. Sponges to wipe away pain. PMID- 1501710 TI - Protein function below 220 K. PMID- 1501711 TI - A small metalloribozyme with a two-step mechanism. AB - An RNA molecule consisting of an asymmetric internal loop of six nucleotides can be rapidly and specifically cleaved by Pb2+ in the presence of Mg2+. The 5' cleavage product terminates with a 3' phosphomonoester generated from a 2',3' cyclic phosphodiester reaction intermediate. This two-step reaction mechanism resembles that of many protein ribonucleases but has not previously been observed for reactions catalysed by RNA. PMID- 1501712 TI - Genetic divergence, speciation and morphological stasis in a lineage of African cichlid fishes. AB - Since their discovery at the turn of the century, the species assemblages of cichlid fishes in the East African Lakes Victoria, Malawi and Tanganyika have fascinated evolutionary biologists. Many models have attempted to account for the 'explosive' evolution of several hundred species within these lakes. Here we report a case of surprisingly large genetic divergence among populations of the endemic Tropheus lineage of Lake Tanganyika. This lineage of six species contains twice as much genetic variation as the entire morphologically highly diverse cichlid assemblage of Lake Malawi and six times more variation than the Lake Victoria species flock. Although it is highly variable in coloration, this group of species and its closest relatives have not undergone appreciable morphological change. The observed geographic pattern of genetic variation suggests that major lake level fluctuations affected the distribution and speciation of this lineage of cichlid fishes. PMID- 1501713 TI - The catalase-peroxidase gene and isoniazid resistance of Mycobacterium tuberculosis. AB - Tuberculosis is responsible for one in four of all avoidable adult deaths in developing countries. Increased frequency and accelerated fatality of the disease among individuals infected with human immunodeficiency virus has raised worldwide concern that control programmes may be inadequate, and the emergence of multidrug resistant strains of Mycobacterium tuberculosis has resulted in several recent fatal outbreaks in the United States. Isonicotinic acid hydrazide (isoniazid, INH) forms the core of antituberculosis regimens; however, clinical isolates that are resistant to INH show reduced catalase activity and a relative lack of virulence in guinea-pigs. Here we use mycobacterial genetics to study the molecular basis of INH resistance. A single M. tuberculosis gene, katG, encoding both catalase and peroxidase, restored sensitivity to INH in a resistant mutant of Mycobacterium smegmatis, and conferred INH susceptibility in some strains of Escherichia coli. Deletion of katG from the chromosome was associated with INH resistance in two patient isolates of M. tuberculosis. PMID- 1501714 TI - Candidate proto-oncogene bcl-3 encodes a subunit-specific inhibitor of transcription factor NF-kappa B. AB - The NF-kappa B subunits p50 and p65 and the product of the rel proto-oncogene are members of a growing class of transcription factors with a unique DNA-binding and dimerization domain. Nuclear transfer of each of these factors is controlled by cytoplasmic inhibitors, and regulated by specific stimuli. The inhibitors I kappa B-alpha and -beta and pp40 recognize either p65 or the c-rel protein. We show here that the proto-oncogene bcl-3, believed to be involved in certain human B cell leukaemias, encodes a protein that functions as an I kappa B-like molecule for native NF-kappa B but is specific for the p50 subunit. The ankyrin repeat domain of the bcl-3 product is shown to mediate complex formation with NF-kappa B dimers by contracting the conserved dimerization domain of NF-kappa B. PMID- 1501715 TI - DNA electrophoresis in microlithographic arrays. AB - We have used optical microlithography to fabricate capped quasi-two-dimensional obstacle courses in SiO2. We report here observations using epifluorescence microscopy of the electrophoresis and length fractionation of large DNA molecules confined in arrays. Simple reptation theory, based on the work of deGennes, predicts that at low electric fields the electrophoretic mobility of a polymer of length L much greater than the persistence length p scales inversely with L (ref. 2). But elongation of the coil in the matrix at sufficiently strong electric fields results in a length-independent electrophoretic mobility. The application of suitably timed pulsed electric fields restores the fractionating power of gels for long molecules but the protocols of pulsed-field electrophoresis are semi empirical because the complex and ill-understood gel matrix plays a critical role in fractionation. Microlithographically constructed obstacle arrays, with their low dimensionality, small volume and extremely reproducible topography, will make it possible to understand the motion and fractionation of large polymer molecules in complex but well characterized topologies. PMID- 1501716 TI - Automated real-time immunoassay of biomolecules. AB - ImmunoDetection is a novel technique combining perfusion chromatography technology with antibodies to perform the steps of an immunoassay in a flow through column format. Sensitive and precise measurements are performed in seconds to minutes using automated liquid chromatography instrumentation. PMID- 1501717 TI - [Word association and schizophrenia--an empirical study]. AB - Since Bleuler's (1911) work on dementia praecox, numerous studies on associative disturbances in schizophrenics have been published. Methodological flaws and difficulties in interpreting the disturbances consistently have brought about a certain dilemma: they are unanimously considered a basic disorder in schizophrenia, but the problem of their reliable evaluation has remained unanswered. 43 schizophrenics, 15 affective psychotics, and 46 normals were investigated in order to compare different forms of the word association test (WAT). The schizophrenics gave less common responses than the normals in the free association task. However, the two groups differed more widely in their performance when asked to respond "individually", "commonly", or using a multiple choice associative test. The affective psychotics were similar in their response behaviour, partly to the schizophrenics (free and common response conditions; multiple-choice test), partly to the normals (individual response condition). The relationship of the WAT to personality characteristics (Eysenck's psychoticism), the influence of psychopathology and the course of the disease, the patients' well-being and self-report of speech and thought disorders are discussed. PMID- 1501718 TI - [Artificial diseases (self-induced diseases)--a review]. AB - Factitious disorders have gained greater significance in all medical specialties during recent years, and continue to pose difficult problems. At present factitious disorders can be divided into four sub-types, the pretence and/or production of somatic and/or psychic medical symptoms being central to all. Apart from disturbance of ego structure the self and the body image (self) a specific disturbance of the doctor-patient relationship is of pathognomonic value. An integrated therapeutic approach (combination of palliative measures, somatic therapy and psychotherapy) seems to be most successful. In the differential diagnosis, factitious diseases have to be delineated from many other diseases in which self-destructive behaviour may occur. PMID- 1501719 TI - [Coping with depressive disorders]. AB - Coping behavior was assessed in 40 depressed patients during their hospitalization and 2 months later. Patients completed an antidepressive activity questionnaire and were interviewed. External assessment and patient self assessment showed significant differences between patients with monopolar or bipolar depressive disorders and those with neurotic/reactive disorders. Patients treated with antidepressants reported more frequent and effective coping behaviors. There is a fundamental difficulty in distinguishing differentiate between symptoms of depression and certain coping behaviors (eg withdrawal). Only a longitudinal analysis of individual cases could help us to differentiate. PMID- 1501720 TI - [Results of electroconvulsive therapy in restrictive indications. A retrospective study of 15 years]. AB - In Tubingen ECT is restricted to severely ill patients who do not respond to other somatic therapies; especially to patients with endogenous depression and pernicious catatonia. Between 1976 and 1990, 45 patients were treated with ECT, of whom 22 suffered from endogenous depression and 10 from pernicious catatonia. Thirteen patients with other diagnoses (schizophrenic and schizoaffective psychoses, borderline schizophrenia and obsessive-compulsive disorder) were treated with ECT for severe depressive states after failure of psychopharmacological therapy. A positive therapeutic response to ECT was observed in 46% of patients with endogenous depression and in all 10 with pernicious catatonia. In the patients with schizophrenia and schizoaffective psychosis, borderline schizophrenia and obsessive-compulsive disorder, an amelioration of the depressive or anxiety syndrome was observed only in individual cases. Side effects of ECT were transit syndromes (20%), reversible amnestic syndromes (20%) and cardiac arrhythmias (6%). According to our results, ECT is highly effective in therapy-resistant endogenous depression and pernicious catatonia, and therefore remains a necessary part of psychiatric therapy. PMID- 1501721 TI - [Prognosis, long-term sequelae and occupational reintegration 2-4 years after severe craniocerebral trauma]. AB - 122 patients with severe head injuries were assessed in terms of their global outcome and social and vocational reintegration 2 to 4 years after trauma. Some patients were studied with regard to physical, psychological, psychosocial, and cognitive long-term consequences. Less than half of the patients (43%) were found to be without employment handicap, while the remainder showed various degrees of occupational difficulty. Most of the patients had significant long-term problems related to cognitive and psychosocial dysfunction. The cognitive disorder, physical handicap, age, and duration of unconsciousness are all important prognostic factors for vocational reintegration, neuropyschological impairment being the single most important factor. PMID- 1501722 TI - [Differential neuroleptic treatment of schizophrenic psychoses in puerperium: advantages of the atypical neuroleptic clozapine]. AB - Clozapine is an atypical neuroleptic drug characterised by specific pharmacological properties and clinical side effects, which are different from those observed with conventional neuroleptics such as drugs of the phenothiazine or butyrophenone classes. This report suggests a new clinical indication for clozapine, based on its negligible influence on plasma prolactin levels: the pharmacotherapy of schizophrenic psychoses in the post-partum period and in patients suffering from acute mastitis. PMID- 1501723 TI - [Critical comments on the contribution by N. Scherbaum and N. Gaspar. Substitution with methadone as a therapeutic approach in the treatment of drug dependent patients]. PMID- 1501724 TI - Virus hepatitis and the kidney. PMID- 1501725 TI - Nosography and immunopathogenesis of viral hepatitis. AB - Five viruses are responsible for the vast majority of cases of viral related hepatitis. They have been named hepatitis A virus (HAV), hepatitis B virus (HBV), hepatitis C virus (HCV), hepatitis D virus (HDV), hepatitis E virus (HEV). The more recent literature concerning the viral structure, the epidemiology, the serological identification, the clinical course and the prevention of each type of hepatitis is reviewed. HBV is not directly cytopathic. Hepatitis is a consequence of the destruction of the virus-infected cells. The efficient elimination of the virus relies on the viral antigenic determinants (HBs, pre-S1, pre-S2, HBc, HBe) and on the immune system of the host. The viral persistence may be caused by defect of the host immunity (interferon production, T and B lymphocyte function) or by factors related to the virus such as a genome mutation (lack of HBe formation). Some evidence suggesting an immunopathogenetic mechanism also for HCV, HDV and HAV is reported. PMID- 1501726 TI - Prevention of viral hepatitis in dialysis units: isolation and technical management of dialysis. AB - The contamination of dialysis machines is an important risk factor for the spread of viral hepatitis in hemodialysis units. The use of reserved machines in separate rooms is a safe prophylactic measure. PMID- 1501727 TI - Renal transplant recipients and chronic liver disease: statistical evaluation of predisposing factors. AB - 278 azathioprine and methylprednisolone (AZA)-treated and 406 ciclosporin (CS) treated patients with a kidney graft functioning for more than 1 year were investigated for the presence of chronic liver disease (CLD), defined as an increase in transaminases of 1.5 times the upper normal limits for a period of at least 12 months. The prevalence of CLD was 36 and 27% in the two groups, respectively. The univariate analysis showed that male sex, alcohol abuse and HBsAg positivity correlated with CLD onset in the AZA group while blood transfusions, length of dialysis treatment, pretransplantation CLD, HBsAg positivity and ferritin levels over 800 ng/ml correlated with CLD onset in CS. The multivariate analysis identified male sex and HBsAg positivity in the AZA group and age over 18 years, high ferritin levels and HBsAg positivity in the CS group as risk factors predictive of CLD onset. Liver failure represented the 4th cause of death in the AZA group but 1 of the 2 most important causes of death in CS in the long term. However, these drawbacks were overcome by the overall low mortality rate in CS. Therefore, renal transplantation should not be refused to patients positive for HBsAg and/or with preexisting liver disease. PMID- 1501728 TI - Prevalence of hepatitides in our hemodialyzed population. AB - We evaluated the prevalence of hepatitis in our hemodialysed population (65 patients, 37 M and 28 F). Screening for A and B hepatitis was tested with the RIA method and research of the anti-HCV with the immunoenzymatic method (Ortho HCV ELISA test of 2nd generation). 15 patients (23.07%) were anti-HCV positive (anti HCV+); 23 (35.38%) showed positivity for 1 or more markers of B hepatitis (HBV+). A meaningful greater prevalence of B virus infections in anti-HCV+ patients (86.66%), compared to negatives, (20.00%) resulted. All non-A, non-B hepatitides are anti-HCV+. The dialytic treatment of the anti-HCV+ patients was meaningfully longer than in the negatives (p less than 0.05). The prevalence of the seropositive patients to B and C virus is not correlated to the number of transfusions, while it is to the number of surgical operations carried out in the predialytic period. This information suggests common pathogenetic mechanisms between the 2 forms of hepatitis and increased probability to find anti-HCV+ with a longer dialytic treatment. PMID- 1501729 TI - Retrospective study on the prevalence of B and non-A, non-B hepatitis in a dialysis unit: 17-year follow-up. AB - To evaluate the prevalence of HBV, non-A, non-B hepatitis (NANBH) and HCV, their evolution and the route of transmission, we performed a retrospective study (17 years) on 65 hemodialyzed patients (mean dialytical age 5 years, range 1-16) who developed acute viral hepatitis. Twenty-six percent of them were affected by HBV; 5 of them (29%) became chronic. Fourty-eight of 65 patients were affected by NANBH; in 1990, 42 of them were tested for antibody to HCV with the C-100 Elisa assay: 27 patients (64%) were positive. Seven of 27 patients demonstrated normal values of ALT. The evaluation of intrafamiliar transmission of HBV showed 8 sexual partners infected. In the family, no one was anti-HCV positive. In agreement with the current literature, we have observed: (1) a decrement in HBV infection; (2) that HCV is the major cause of NANBH; its rate of chronicity is over 50%; (3) that the prevalent mode of HCV transmission is the parenteral route while the sexual route seems to be negligible. PMID- 1501730 TI - Non-A, non-B hepatitis in patients on dialysis: retrospective evaluation of measures taken to limit the diffusion of the virus. AB - 329 patients were evaluated from 1978 to 1990. 40 new cases of non-A non-B hepatitis were observed, all regarding patients on hemodialysis. Since the beginning of 1989, we introduced measures to limit the diffusion of the virus: reduction to a minimum of blood transfusions and a new disinfection protocol for monitors, instruments and surroundings. Of the 40 new cases, 30 took place between January 1985 and March 1989, only 2 later. If we consider the annual incidence before and after the introduction of preventive measures, we can observe a significant reduction in NANB hepatitis incidence in the last 2 years. PMID- 1501731 TI - Anti-hepatitis C virus epidemiological study in two dialysis centers in Florence. AB - We studied the prevalence and incidence of anti-hepatitis C virus (HCV) antibodies in 350 patients during 15 months and looked for some risk factors. We found a significant correlation between anti-HCV positivity and length of dialysis treatment and treatment in more than one center. We propose some prophylactic rules. PMID- 1501732 TI - Glucose and insulin metabolism in uremia. PMID- 1501733 TI - Immunosuppression by T cell antibodies in renal transplantation. PMID- 1501734 TI - Pharmacokinetics of recombinant human erythropoietin in dialysis patients after single and multiple subcutaneous administrations. AB - The pharmacokinetics of recombinant human erythropoietin (rhEPO) were evaluated after single intravenous and single subcutaneous administration of 40 U/kg to 8 patients with dialysis treatment. All patients suffered from renal anemia with a hematocrit less than or equal to 24% and were treated with 40 U/kg rhEPO subcutaneously, three times a week for 6 weeks. At the end of the treatment period, kinetics of rhEPO were repeated. After the initial subcutaneous rhEPO dose, the following results were obtained: maximum plasma concentration 39.5 (26.7-56.9) U/l, area under the curve (AUC) 1,122 (582-3,220) U.h.1-1 and terminal half-life 13.2 (2.6-53.1) h. The corresponding data after multiple rhEPO doses were: maximum rhEPO plasma concentration 26.3 (9.4-49.1) U/l, AUC 724 (407 1,464) U.h.1-1 and terminal half-life 14.2 (3.5-24.4) h. There were no statistical significant differences between the two investigations. From the present study, it can be concluded that after a treatment period of 6 weeks with multiple subcutaneous rhEPO doses, rhEPO absorption as well as rhEPO elimination are unchanged. PMID- 1501735 TI - Effectiveness and safety of recombinant human erythropoietin in predialysis patients. Austrian Multicenter Study Group of r-HuEPO in Predialysis Patients. AB - Experience with erythropoietin in the treatment of anemia in predialysis patients is limited. A practical treatment regimen which minimized the number of outpatient visits was investigated. The Austrian multicenter study included 123 patients. At baseline, the treatment protocol mandated once weekly the administration of 10,000 U recombinant human erythropoietin (r-HuEPO) subcutaneously. The follow-up period was 3 months, and dose adjustments were made at montly intervals. At baseline, the mean values for creatinine were 6.2 +/- 0.2 mg/dl, and for hemoglobin (Hb) 9.0 g/dl. During 3 months of therapy, mean Hb increased to 10.8 g/dl and creatinine to 6.6 mg/dl. The initial r-HuEPO weekly dose was 10,000 U. The mean dose after 3 months was 9,000 +/- 4,000 U. There was no significant alteration of the slope of the reciprocal creatinine curve or of blood pressure values. No side effects occurred during the 3-month treatment period. In conclusion, the results of this multicenter trial demonstrate that using a simple once-weekly subcutaneous treatment regime, r-HuEPO can be administered safely and effectively in predialysis patients. PMID- 1501736 TI - Anemia and chronic renal failure: a therapeutical approach by reduced glutathione parenteral administration. AB - Authors report on the effect of reduced glutathione parenterally administered on the anemic status in patients suffering from chronic renal failure and undergoing hemodialysis. Twenty patients were studied for 180 days and were divided into two age- and sex-matched groups. The first group (10 patients) received placebo, the second group (10 patients) received the treatment (1,200 mg of reduced glutathione). Reduced glutathione and placebo were given for 120 days in a randomized double-blind fashion and the following measurements were performed: red blood cells reduced and oxidized glutathione, plasma reduced and oxidized glutathione, hematocrit, hemoglobin, reticulocytes, serum iron, transferrin, indirect bilirubin, urea, creatinine, calcium, phosphate, parathyroid hormone and alkaline phosphatase. In the treated group, during the supplementation period, there was an increase in the levels of red blood cells and plasma reduced glutathione, hematocrit and hemoglobin and a concomitant decrease in plasma oxidized glutathione and reticulocytes with a maximum effect on the 120th day of therapy. In the placebo-treated group there were no significant variations of the parameters considered during the study period. When the therapy, on patients undergoing treatment, was terminated there was a drop in the analyzed parameters, which fell to pretreatment values at the subsequent controls. These findings seem to indicate that reduced glutathione could represent a useful drug in the treatment and management of anemia in patients affected by chronic renal failure. PMID- 1501737 TI - Comparison of lipids, apoproteins and associated enzyme activities between diabetic and nondiabetic end-stage renal disease. AB - Lipids, apoproteins and associated enzyme activities in type 2 diabetic end-stage renal disease (ESRD) were compared with that in nondiabetic ESRD and normal controls. Of the 40 uremic patients with non-insulin-dependent diabetes mellitus, 20 patients were receiving stable continuous hemodialysis treatment (CHT). Of the 39 patients with nondiabetic ESRD, 21 were undergoing CHT. Patients with nondiabetic ESRD exhibited elevated levels of serum triglyceride and a marked reduction in high-density-lipoprotein (HDL) cholesterol. Concentrations of serum apolipoprotein (Apo) C-3 were higher than in controls, whereas mean levels of serum Apo E were lower. The concentrations of serum Apo A-1 and Apo A-2 decreased with diminished lecithin: cholesterol acyltransferase activity. Lipoprotein lipase activity decreased in undialysed patients, and hepatic triglyceride lipase activity decreased significantly throughout the observation. Patients with diabetic ESRD exhibited elevated serum Apo B and normal serum Apo E levels, besides the lipid and Apo abnormalities observed in nondiabetic ESRD. Moreover, a prominent reduction in serum Apo A-1 was found in dialysed diabetic patients. The Apo B/Apo A-1 ratio was significantly higher in diabetic ESRD than in nondiabetic patients undergoing CHT. These results indicate that lipid abnormalities are accelerated in diabetic ESRD and may constitute a serious risk for the development of atherosclerosis. PMID- 1501738 TI - Heparan sulfate proteoglycans are lost in patients with diabetic nephropathy. AB - The pathogenesis of diabetic nephropathy relative to the changes in the glomerular extracellular matrices was investigated. Renal tissues from 10 diabetic patients were immunostained with antibodies directed against heparan sulfate proteoglycans (HS-PGs), laminin, type IV collagen and fibronectin. Seven patients were nephrotic and had advanced glomerulosclerosis with nodular lesion, while the other 3 had no renal manifestations or minor glomerular tissue alterations. Controls included kidneys removed from patients with renal tumors and specimens obtained by renal biopsy from patients with IgA nephropathy. Relationships among proteinuria, intensity of fluorescence and glomerular changes were studied. In diabetes 3 patients with minor glomerular lesions were found to have no changes in various components of extracellular matrices. A marked reduction in the intensity of staining with anti-HS-PG antibodies was observed in renal specimens from patients with nodular glomerulosclerosis and proteinuria, while a mild decrease in the intensity of fluorescence was observed in tissues stained with antilaminin antibodies. An increase compared to normal control sample findings in type IV collagen and fibronectin was observed in the mesangium of sclerosing glomeruli. No loss of HS-PG was observed in patients with IgA nephropathy. These results indicate that glomerular extracellular matrix HS-PG is lost in association with diabetic nephropathy; this loss results in alteration of the charge-selective properties of glomerular capillaries. This alteration may, in part, be the cause of the proteinuria associated with diabetic nephropathy. PMID- 1501739 TI - Determinants of intact parathyroid hormone and free 1,25-dihydroxyvitamin D levels in mild and moderate renal failure. AB - Parameters of calcium and phosphate metabolism were measured in 27 patients with mild renal failure [glomerular filtration rate (GFR) 40-90 ml/min], 12 patients with moderate renal failure (GFR 20-39 ml/min) and in 12 healthy subjects. GFR was determined by technetium-99m diethylenetriamine penta-acetic acid clearance. Intact parathyroid hormone (PTH) was measured by a sensitive immunochemiluminometric assay and somatomedin-C was determined by radioimmunoassay. Both 1,25-dihydroxyvitamin D [1,25(OH)2D] and vitamin-D-binding protein were measured allowing calculation of the free 1,25(OH)2D index. By linear regression and multivariate analysis, PTH was negatively and independently correlated with GFR, plasma bicarbonate and 25-hydroxyvitamin D [25(OH)D] while free 1,25(OH)2D was positively correlated with GFR. Increased PTH secretion and reductions in 1,25(OH)2D were present in mild renal failure patients before any changes in plasma calcium, phosphate and bicarbonate were noted. Plasma alkaline phosphatase was significantly higher in mild chronic renal failure patients compared to normal subjects, possibly indicating early effects of the secondary hyperparathyroidism on the skeleton. Somatomedin-C did not correlate with the free 1,25(OH)2D index or a measure of 1,25(OH)2D production. It is concluded that the secondary hyperparathyroidism which occurs very early in the onset of chronic renal failure may be due to a reduction in the circulating concentration of 1,25(OH)2D consequent upon the renal failure. Low plasma bicarbonate and 25(OH)D also appear to be determinants of a raised PTH concentration. The compensatory increase in PTH presumably maintains extracellular calcium and phosphate levels constant but with possible deleterious effects on the skeleton. PMID- 1501740 TI - Decreased renal clearance of xanthine and hypoxanthine in a patient with renal hypouricemia: a new defect in renal handling of purines. AB - Renal handling of urate, xanthine and hypoxanthine was studied in a hypouricemic patient who had increased plasma concentrations of xanthine and hypoxanthine. The patient, a 50-year-old man, had been suffering from Parkinson's disease, while neither systemic disorders nor particular renal diseases known to affect plasma purine levels were found. His serum urate level was 58 +/- 6 mumol/l (healthy controls for males, 310 +/- 48 mumol/l, mean +/- SD) and the renal uric acid clearance was 3 times higher than that of the controls, establishing a diagnosis of renal hypouricemia. Xanthine and hypoxanthine concentrations in the plasma were elevated to 1.3 +/- 0.1 mumol/l (controls, 0.5 +/- 0.3) and 5.9 +/- 3.5 mumol/l (controls, 1.6 +/- 0.4), respectively. Both renal xanthine and hypoxanthine clearance was only half the value of the controls, indicating reduced urinary excretion of xanthine, and hypoxanthine appears to be responsible for their elevation in plasma. A probenecid loading test revealed no response of urinary urate excretion but normal responses of xanthine and hypoxanthine excretion. However, urinary excretion of urate, xanthine or hypoxanthine did not respond at all to pyrazinamide administration. These findings indicate that the patient had a defective renal handling of xanthine and hypoxanthine as well as urate. PMID- 1501741 TI - Two cases in whom pyrazinamide does not inhibit the uricosuric action of benzbromarone. AB - The 2 subjects were a diabetic male with renal hypouricemia and a healthy male with normouricemia. In these subjects, 200 mg of benzbromarone increased fractional uric acid clearance (FUa) and 3.0 g of pyrazinamide decreased FUa. However, pyrazinamide did not inhibit the uricosuric action of benzbromarone at all on the administration of 3.0 g of pyrazinamide together with 200 mg of benzbromarone. These results indicated that in these cases, the relative role of each component could not be determined on the basis of the hypothetical four component model. PMID- 1501742 TI - Role of platelet cytosolic calcium in regulation of blood pressure in patients on chronic hemodialysis. AB - We measured blood pressure, platelet cytosolic calcium concentration ([Ca2+]i) and vasoactive hormones in 20 anuric normotensive patients on chronic hemodialysis (HD) to clarify the role of cytosolic calcium in regulation of blood pressure. All measurements were performed at the end of HD (post-HD) and at the beginning of the next HD (pre-HD). During the HD-HD interval, mean blood pressure increased from 85 +/- 4 to 94 +/- 4 mm Hg (mean +/- SEM, p less than 0.05), but the median [Ca2+]i in platelets did not show any significant change (133 +/- 5 vs. 136 +/- 5 nmol/l). Although all patients were within their ideal body weight at post-HD, platelet [Ca2+]i did not correlate with mean blood pressure. By contrast, platelet [Ca2+]i correlated with mean blood pressure (r = 0.489, p less than 0.05) at pre-HD. Moreover, platelet [Ca2+]i at post-HD also correlated with changes in mean blood pressure during the HD-HD interval (r = 0.532, p less than 0.05). In addition, there were negative correlations between platelet [Ca2+]i and plasma renin activity both post- and pre-HD (r = -0.652, p less than 0.005; r = 0.673, p less than 0.005; respectively). These results suggest that cytosolic calcium plays important roles in regulation of renin secretion and in the elevation of blood pressure induced by volume expansion in patients on chronic HD. PMID- 1501743 TI - Trace elements in dialysis fluids and assessment of the exposure of patients on regular hemodialysis, hemofiltration and continuous ambulatory peritoneal dialysis. AB - Forty-four elements (Al, Sb, As, Ba, Be, B, Br, Cd, Ce, Co, Cr, Cs, Cu, Eu, Ga, Au, Hf, In, Ir, Fe, La, Lu, Mn, Hg, Mo, Nd, Ni, Pb, Rb, Sm, Sc, Se, Ag, Sr, Ta, Tb, Tl, Th, Sn, W, U, V, Zn, Zr) have been determined in the dialysate for hemodialysis (HD) and fluids for hemofiltration (HF) and continuous ambulatory peritoneal dialysis (CAPD). Multiple determinations have been performed for each dialysis fluid. Several trace elements (TE) showed remarkably elevated average levels; moreover, different bathes of the same commercial product may present a wide variability in TE concentration. The data point out the pivotal role of dialysis fluids in contributing to TE imbalance in dialysis patients and allow the assessment of the potential element exposure of patients on regular dialytic treatment. Patients on HD treatment would be exposed on a weekly basis to milligrams of Al, B, Ba, Br, Cu, Fe, Ni, Pb, Rb, Sr and Zn; on HF, the highest exposures are due to Al, B, Br, Fe, Pb and Zn; on CAPD to B, Br, Fe and Zn. The weekly exposure for several TE appears to be 50- to 12,000-fold higher than the corresponding values on the amount absorbed via the diet (HD: Au, Ba, Be, Ce, Ga, La, Sc, Ta, Th, V, Zr; HF: Be, Ce, Ta, Th, V, Zr; CAPD: Au, Be, Ce, Ga, V, Zr).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1501744 TI - Glutathione monoethyl ester moderates mercuric chloride-induced acute renal failure. AB - Glutathione (GSH)-dependent reactions are an important cellular defense against ischemic or oxidative injury, although their role in toxin-induced renal cellular injury is less clear. Because of the known sulfhydryl reactivity of mercury (M), we hypothesized that GSH could modify mercuric chloride (MC)-induced acute renal failure (ARF). Therefore, we evaluated the effects of glutathione monoethyl ester (GE), which produces high intrarenal levels of GSH, on the nephrotoxicity of MC. GE treatment in normal rats did not alter their creatinine clearance (CCr), fractional sodium (CNa/CCr) or lysozyme (CLy/CCr) excretion, but histologically resulted in prominent proximal tubular vacuolization. GE pretreatment in rats with MC-induced ARF resulted in partial preservation of their CCr, CNa/CCr and CLy/CCr. Renal histology also demonstrated a reduction in tubular necrosis. M content in the renal cortex 3 following MC was lower in the MC + GE group, but levels were higher in the liver and inner stripe/inner medulla as compared to animals receiving MC alone. No differences were seen in the outer stripe at 3 h or in any of the tissues 24 h following MC injection. Thus, GE moderated MC induced ARF, likely by providing a large intracellular sulfhydryl pool and thereby reducing M reactivity with endogenous cellular proteins and enzymes. PMID- 1501745 TI - Synthesis of fibronectin by isolated glomeruli from nephrectomized hypertensive rats. AB - The accumulation of extracellular matrix (ECM) is an important feature of most forms of progressive glomerular diseases. In order to examine the relationship between ECM synthesis and glomerulosclerosis, we evaluated fibronectin synthesis by glomeruli with the immunoprecipitation of conditioned media from isolated glomeruli in 5/6 nephrectomized spontaneously hypertensive rats (5/6N-SHR). There was no difference in blood pressure between 5/6N-SHR and control SHR throughout the experiment. Two weeks after the nephrectomy, most of the glomeruli were intact and no difference in the synthesis of fibronectin was observed between either groups. Twenty weeks after the nephrectomy, marked glomerulosclerosis associated with an increase in urinary protein was revealed in 5/6N-SHR but no glomerular lesions in control SHR. The synthesis of fibronectin by isolated glomeruli increased in 5/6N-SHR compared to control SHR. The administration of enalapril or hydralazine + reserpine + hydrochlorothiazide markedly attenuated the glomerular sclerosis and urinary protein excretion to a comparable degree, although the later therapy reduced blood pressure more effectively. These antihypertensive therapies also suppressed fibronectin synthesis in the 5/6N-SHR group at week 20. In conclusion, increased synthesis of glomerular fibronectin appeared to contribute to the glomerulosclerosis caused by subtotal nephrectomy and hypertension. PMID- 1501746 TI - Hypoglycemia during hemodialysis in diabetics treated with insulin. PMID- 1501747 TI - Variability of urinary chloride--a clue to diuretic abuse. PMID- 1501748 TI - Possible mechanisms underlying potentiating effects of iron chelators in hematopoietic response to erythropoietin. PMID- 1501749 TI - Multiple European wasp stings and acute renal failure. PMID- 1501750 TI - Africanized bee stings and pathogenesis of acute renal failure. PMID- 1501751 TI - IgA nephropathy in two HLA-identical brothers and acute, diffuse proliferative glomerulonephritis in the third, HLA-different brother. PMID- 1501752 TI - Varicella pneumonitis in children with hemodialysis. PMID- 1501753 TI - Urticaria-associated recurrent glomerulonephritis with a favorable response to indomethacin. PMID- 1501754 TI - What is a true cause of high level of urinary beta-2-microglobulin after renal transplantation? PMID- 1501755 TI - Core biopsy of the transplanted kidney using 1.1-mm needles: results and comparison with the Tru-Cut technique. PMID- 1501756 TI - [Research and surgical treatment of epilepsy]. AB - The currently available surgical procedures for the treatment of epilepsy, from fundamental data to therapeutic results, including various means of investigation are reported. The work is based on a review of the literature and on the cases studied by the two teams from the Universities of Montreal and Bordeaux who share the same concept of epilepsy surgery. The patient groups of the two teams include 316 S.E.E.G., 214 cortectomies, 39 callosotomies and 2 multiple sub-pial transsections. In the first part, the authors attempt to demonstrate that the epileptic focus corresponds to the region where the seizures arise, that this focus is not directly comparable to the region where inter-ictal spikes are recorded and sometimes becomes autonomous from the causal lesion. The epileptic phenomenon has a definite harmful effect on cerebral functions and a probable self-aggravating potential. The second chapter summarizes the clinical data on which the indications and contraindications are based. These obviously depend on whether the intervention is intended to be curative or palliative. Various non invasive and invasive investigations are then reviewed, according to their relative importance and the experience of each team. The main points developed are: the electroclinical correlations during seizures, the symptomatological data for differentiating between temporal and frontal lobe seizures, the contribution of M.R.I. in demonstrating the epileptogenic and epileptic lesions, the electrophysiological information suggesting that S.E.E.G. remains the most informative mean of investigation. The various methods of investigation of assessing electrical, functional (cerebral blood flow, metabolism) and morphological aspects of epilepsy, supply non-redondant findings about the localisation of the epileptic focus. The chapter on surgical techniques mainly discusses the various modes of implantation of subdural and intracerebral electrodes and reports the same rate of morbidity in both cases. Orthogonal teleradiography is still perfectly suited to the implantation of intracerebral electrodes. S.E.E.G. is still the most anatomically precise technique. However, in certain conditions, extraoperative E.Co.G. is more adequate. New surgical modalities have recently appeared such as the multiple subpial transsections which allow treatment of epileptic foci unapproachable by cortectomy and such as modified techniques of hemispherectomy, which by decreasing morbidity, renew interest in them. In the chapter on surgical results, the authors emphasize the methodological problems of evaluation that partly account for their wide variability. The results obtained with the various surgical modalities are reviewed. The outcome in cortectomies is discussed at length in terms of the data from the literature as well as the results reported by both teams.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1501757 TI - Modulation of the in vitro electrophysiological effect of corticosterone by extracellular calcium in the hippocampus. AB - The electrophysiological effects of various concentrations of corticosterone (CORT) on the hippocampus were investigated using extracellular recordings from CA1 hippocampal slice preparations subjected to four different extracellular concentrations of calcium. In all cases, the CORT effect was manifested by a PS amplitude decrease without affecting the slope of either the input volley or the EPSP. Our results showed that, for the lowest extracellular calcium concentrations (1.3 and 2.5 mM), the inhibitory effect of CORT on the PS amplitude appeared only with the supra-physiological 10,000 nM CORT concentration, whereas for the highest ones (3.13 and 5.32 mM) this effect was observed, respectively, with 5 and 0.05 nM CORT concentrations. The antiglucocorticoid RU 486, used in combined application with CORT, blocked the electrophysiological effect of CORT. The possible involvement of calcium dependent mechanisms at the CORT receptor level or in the final cellular response are discussed. PMID- 1501758 TI - Effects of angiotensin II on LHRH release, as measured by in vivo microdialysis of the anterior pituitary gland of conscious female rats. AB - The present experiments assessed the effects of central administration of angiotensin II (Ang II) on mean levels of luteinizing hormone-releasing hormone (LHRH) in the extracellular fluid of the anterior pituitary gland, monitored by in vivo microdialysis. Ovariectomized rats were tested under two conditions: (1) nonhormone-treated where Ang II infusion inhibits luteinizing hormone (LH) release, and (2) ovarian hormone-treated where Ang II stimulates LH secretion. Animals were ovariectomized and chronic guide cannulae were implanted, one into the lateral cerebral ventricle for infusion of Ang II and one directed toward the anterior pituitary gland for the insertion of the microdialysis probe. Approximately 1 week later, the dialysis probe was inserted and cemented into place. The length of the dialysis probe transected the pituitary gland from its dorsal to ventral aspects. Dialysis samples were collected at 15-min intervals. Levels of LHRH were continuously monitored in nonhormone-treated animals, prior to and during intracerebroventricular (i.c.v.) infusion of Ang II. The dialysis probe was removed at the end of the experiment. One week later, the same animals were treated with estrogen and progesterone and dialysis of the anterior pituitary gland was performed 3 days later using a protocol identical to the first dialysis sampling session. A separate group of animals was tested to confirm the effects of lateral ventricle infusion of this dose of Ang II on LH release. There were no detectable values of LHRH in dialysis samples from non hormone-treated animals.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1501759 TI - Angiotensinogen secretion by single rat pituitary cells: detection by a reverse haemolytic plaque assay and cell identification by immunocytochemistry. AB - A reverse haemolytic plaque assay (RHPA) for angiotensinogen was developed in rat hepatoma H4 cells and applied to investigate the possible secretion of angiotensinogen from rat pituitary cells in primary culture. Over a 24-hour incubation period in Cunningham chambers plaques with a mean area of 2,800 +/- 430 and 590 +/- 220 microns2/plaque (SD, n = 6) formed around all viable H4 cells and 2.8 +/- 0.59% of viable pituitary cells respectively. As a positive control PRL secretion from lactotrophs was routinely checked by the RHPA and shown to form plaques with a mean area of 4,050 +/- 1,850 microns2/plaque after a 4-hour incubation. By comparing plaque size in H4 cells with angiotensinogen release in cell culture, as quantified by radioimmunoassay, the secretion rate of angiotensinogen from pituitary cells was calculated as 22 +/- 8 ng/10(6) cells/24 h. Plaque-forming cells consisted of two morphologically distinct populations; 78% being small cells (less than 6 microns diameter) containing little cytoplasm and 22% were large (greater than 9 microns diameter) cells with an abundant cytoplasm. Immunocytochemical staining of pituitary cells after formation of plaques with anti-angiotensinogen, anti-LH and anti-PRL antiserum showed that the large plaque-forming cells were gonadotrophs and none were lactotrophs. All plaque-forming cells stained for angiotensinogen but only 44% of the viable cells which stained for angiotensinogen actually formed plaques. The possibility that cellular angiotensinogen was imported from extracellular sources was investigated by incubation of pituitary cells with pure 125I-angiotensinogen for periods up to 24 h. No uptake of the radiolabelled protein was found.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1501760 TI - Influences of hypothyroidism on TRH concentrations and preproTRH mRNA levels in rat hypothalamus: a simple and reliable method to detect preproTRH mRNA level. AB - To gain further insight into the regulation of hypothalamic TRH by thyroid hormones, we measured TRH concentration in specific hypothalamic nuclei and preproTRH mRNA levels in the anterior hypothalamus. Adult male rats were decapitated 1, 7, 14 days after thyroidectomy. Micropunches by the method of Palkovitz from seven hypothalamic nuclei and median eminence were used for measurement of TRH by radioimmunoassay. As compared with normal levels, TRH concentration significantly decreased in the median eminence and five hypothalamic nuclei including paraventricular nucleus (PVN), posterior nucleus, anterior nucleus, arcuate nucleus, and ventromedial nucleus pars lateralis, by 7 days after thyroidectomy. No significant changes were observed in dorsomedial nucleus or ventromedial nucleus pars medialis until 14 days after thyroidectomy. A rapid and simple method to detect specific mRNA for preproTRH was developed using the polymerase chain reaction and a single anterior hypothalamic section. PreproTRH mRNA levels in the anterior hypothalamus increased approximately twice 7 days after thyroidectomy. These data indicate that thyroidectomy caused a marked increase in preproTRH mRNA levels of the anterior hypothalamus, while it significantly reduced TRH concentrations not only in PVN and median eminence but also in other specific hypothalamic nuclei, suggesting that these nuclei might be involved in the thyrotropin regulation in the hypothalamus. PMID- 1501761 TI - Evidence that circadian variations of circulating melatonin levels in fetal and suckling rats are dependent on maternal melatonin transfer. AB - Although the circadian variation of melatonin content in the pineal gland appears during the 3rd week of extrauterine life, recent studies suggest that the fetus perceives the day length through maternal melatonin transfer. Accordingly, we determined serum melatonin concentrations in pregnant and lactating rats and in their offsprings during the day (D) and at night (N). As compared with nonpregnant adult female rats (D: 6.0 +/- 0.5 and N: 112.0 +/- 5.0 pg/ml), significant increases of serum melatonin concentrations, both during the day and at night, were observed in 21-day pregnant (D: 21.0 +/- 2.6 and N: 222.0 +/- 7.2 pg/ml) and in 10-day (D: 20.0 +/- 2.6 and N: 145.0 +/- 12.3 pg/ml) and 20-day (D: 19.0 +/- 1.2 and N: 140.0 +/- 8.0 pg/ml) lactating animals, while a profound decrease was found in 5-day (D: 13.0 +/- 1.0 and N: 50.0 +/- 5.6 pg/ml) lactating rats. In addition, melatonin levels were significantly higher during the night than during the day in all the experimental groups. High levels and circadian variation of serum melatonin were detected also in 21-day-old fetuses (D: 13.0 +/ 0.8 and N: 108.0 +/- 4.8 pg/ml) and in 5- and 10-day-old suckling (in 5-day-old, D: 13.0 +/- 0.6 and N: 71.0 +/- 3.1 pg/ml; in 10-day-old, D: 17.0 +/- 1.4 and N: 63.0 +/- 3.8 pg/ml) rats.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1501762 TI - Hypothalamic regulation of microtubule-associated protein phosphorylation in lactotrophs. AB - Endogenous phosphorylation of microtubule-associated proteins was examined in cultures of anterior pituitary cells from estradiol-treated rats. The cells were incubated for 1 h with 32P-orthophosphate and challenged for different times with removal of dopamine (DA), the addition of TRH in the presence of DA, or the transient removal of DA followed by addition of TRH. Microtubules were bundled by taxol followed by electrophoretic separation of the phosphorylated proteins and autoradiography. Within 10 s to 1 min of any of the treatments increased labeling of eight phosphoproteins (64, 80, 95, 110, 125, 155, 205 and 300 kDa) appeared in autoradiograms. The pattern of labeling in response to DA withdrawal was longer lasting than that induced by TRH, whose effect disappeared by 10 min. The administration of TRH after a transient 10-min withdrawal of DA increased the magnitude and prolonged the duration of the effect of TRH. The 80-kDa microtubule associated protein comigrated with the well characterized heat-stable, acid soluble protein substrate for protein kinase C (PKC). The migration of the proteins following two-dimensional polyacrylamide gel electrophoresis and autoradiography was identical. Furthermore, the sequential extraction of microtubule-associated proteins followed by extraction of heat-stable, acid soluble proteins showed a phosphoprotein of Mr 80 kDa. These observations suggest that the ubiquitous, heat-stable, acid-soluble 80-kDa phosphoprotein that is a specific substrate for PKC is associated with microtubules in lactotrophs. Furthermore, the levels of microtubule-associated phosphoprotein are increased following hormonal activation of PKC, although it is unclear whether this increase represents translocation of the phosphoprotein or phosphorylation of a previously associated protein. PMID- 1501763 TI - The chromogranins A and B: the first 25 years and future perspectives. PMID- 1501764 TI - Slowing of electroencephalogram and choline acetyltransferase activity in post mortem frontal cortex in definite Alzheimer's disease. AB - Twenty-five (96%) of 26 patients with histologically verified moderate to severe Alzheimer's disease had abnormal electroencephalograms. The patients with the slowest (5-6 Hz) dominant occipital rhythms had significantly lower choline acetyltransferase activity in the post mortem frontal cortex than the patients with highest rhythm (8-9 Hz) (analysis of covariance adjusted for the neuropsychological test score). Concentrations of dopamine, noradrenaline or serotonin in the frontal cortex did not differ in the patient groups with the slowest and highest rhythms. Neither did scores of senile plaques or neurofibrillary tangles differ between these groups. In Alzheimer patients, the frequency of the dominant occipital rhythm correlated with the total score of the neuropsychological test (r = 0.58, P less than 0.01) and with the subscales of praxic functions and expressive speech, memory and general reasoning. The results suggest that the cholinergic deficit may contribute to the slowing of the electroencephalogram found in patients with Alzheimer's disease. PMID- 1501765 TI - The barbiturate thiopental reduces ATP levels during anoxia but improves electrophysiological recovery and ionic homeostasis in the rat hippocampal slice. AB - The barbiturate anesthetic thiopental enhances recovery of the evoked population spike recorded from rat hippocampal slices after short periods of anoxia. Thiopental reduces changes in sodium, potassium and calcium but enhances the fall in ATP levels during anoxia. The postsynaptic population spike recorded from the CA1 pyramidal cell region of the slices treated with thiopental (600 microM) recovered to 67% of the preanoxic amplitude after 3.5 min of anoxia. There was less recovery (24%) when a lower concentration of thiopental (250 microM) was used. Untreated slices recovered to only 10% of their preanoxic amplitude after 3.5 min of anoxia. Other studies have demonstrated that maintaining ATP levels during anoxia may be an important mechanism of protection. In contrast to those studies, thiopental was protective although it enhanced the fall of ATP levels after 3.5 min of anoxia in the CA1 region and after 3.5 and 5 min in the dentate region. Thus enhanced recovery of the population spike with thiopental is not due to its preservation of ATP levels. This result allows a clear separation of improved ATP levels during anoxia from other mechanisms of protection. We therefore looked for other mechanisms of protection. Sodium and potassium levels were measured after 10 min of anoxia. In untreated tissue, sodium levels in the slice rose and potassium levels fell significantly. In thiopental-treated tissue, changes in sodium and potassium caused by anoxia and by veratridine under normoxic conditions were significantly reduced. During anoxia calcium-45 uptake increases; thiopental significantly reduces this uptake.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1501766 TI - Desensitization of GABA-induced currents in cultured rat hippocampal neurons. AB - The basic characteristics of desensitization of the GABAA receptor were investigated in cultured rat hippocampal neurons (three days to four weeks in vitro) using whole cell patch clamp techniques. GABA at 10-500 microM was perfused on to neurons for 30 or 60 s, with 60 s intervals of wash with control bath solution between perfusions. Desensitization, evaluated by peak-to-plateau ratio and time constants of current decay (tau), was dose-dependent and culture age-dependent. Desensitization was observed as early as three days in culture, the earliest time tested. At all ages, higher concentrations of GABA induced both larger and faster desensitization. Desensitization was markedly voltage-dependent and decreased with depolarization; peak-to-plateau ratio went from 6.3 to 1.4 and tau went from 4.6 to 26.8 s when holding potentials were changed from -80 mV to +30 mV. Low concentrations of GABA (1-2 microM) perfused for 2-60 s, which did not induce any current, had no effect on the maximal response nor desensitization produced by a subsequent application of 100 microM GABA. This finding suggests that GABA receptors were not desensitized without first being activated. PMID- 1501767 TI - Biochemical and immunohistochemical demonstration of a tightly bound form of prostaglandin E2 in the rat brain. AB - Basal levels of prostaglandin E2 in the rat brain were determined by radioimmunoassay to be 0.68-0.79 pmol/g brain. About one-third of the prostaglandin E2 (0.23-0.28 pmol/g) was resistant to extraction with ethanol, but could be recovered with a mixture of ethanol and 1 N HCl (9:1, v/v), indicating that a tightly bound form of prostaglandin E2 exists in the brain. The amount of the bound form of prostaglandin E2 was almost unchanged by pentylenetetrazole induced convulsion or by transcardial perfusion with a formaldehyde solution, although these treatments resulted in 40- to 80-fold increases in prostaglandin E2 content extracted with ethanol at neutral pH. A polyclonal antibody against prostaglandin E2-albumin conjugates recognized the bound form of prostaglandin E2, giving a punctate appearance in many neuronal cell bodies in the brain. Although almost all of the neuronal perikarya were immunoreactive for prostaglandin E2, intense immunoreactivity was observed in the mitral cell layer of the olfactory bulb, layer V of the cerebral neocortex, anterodorsal and reticular nuclei of the thalamus, supraoptic, paraventricular, accessory neurosecretory and lateral mammaillary nuclei of the hypothalamus, mesencephalic trigeminal nucleus, nucleus of the trapezoid body and deep cerebellar nuclei. When the cerebral neocortical regions were observed electron microscopically, immunoreaction products were seen as fine granules which were clustered into small patches in the cytoplasm of neuronal cell bodies and proximal dendrites. No immunoreaction products were seen in glial cells or endothelial cells. These results suggest that prostaglandin E2 is involved in fundamental processes of neurons. PMID- 1501768 TI - The tuned displacement response of the hearing organ is generated by the outer hair cells. AB - The motile responses of the guinea-pig hearing organ in response to a tone applied to the ear were measured by laser interferometry. Two types of responses can be recorded: (i) a vibration at the frequency of the applied tone; and (ii) a displacement response consisting of a shift in the position of the organ surface. The purpose of this study is to characterize the displacement response. The results are as follows. There is a relationship between the frequency of highest sensitivity (best-frequency) of the displacement response and the site from which it is recorded. High best-frequencies are noticed at more basal locations, low best-frequencies towards the apex. The displacement response is more frequency selective than the vibration response. The displacement response is observed within physiological sound pressure levels. Its sharpness is dependent on the stimulus intensity, it shows biological variability and can be manipulated by drugs that are known to modify the receptor potential of the sensory cells, or to interfere with outer hair cell motility. These results suggest that the displacement response is an important step in the transduction process in the mammalian hearing organ and that it is generated by the motile action of the outer hair cells. PMID- 1501769 TI - Expression of c-fos-like immunoreactivity in brainstem after meningeal irritation by blood in the subarachnoid space. AB - The expression of c-fos protein was examined by immunohistochemistry in serial sections of brainstem following the instillation of either autologous arterial blood (0.3 ml) or mock cerebrospinal fluid (0.3 ml) through a catheter placed in the cisterna magna, or following catheter placement alone in pentobarbital anesthetized Sprague-Dawley rats. After injection, blood was distributed within the subarachnoid space surrounding the brainstem and in the region of the circle of Willis. c-fos protein-like immunoreactivity was present at 1 h, peaked at 2 h and decreased by 8 h. At 2 h, immunoreactivity was strongly expressed within trigeminal nucleus caudalis (lamina I, IIo), as well as within nucleus of the solitary tract, area postrema, ependyma, pia mater and arachnoid in every animal. Moderate labeling was found in parabrachial nucleus, medullary lateral reticular nucleus and central gray. Sparse labeling was present in trigeminal nucleus caudalis (lamina III-V) and trigeminal nucleus interpolaris; few or no labeled cells were detected in other parts of the trigeminal nuclear complex, thalamus, cerebral cortex, cerebellar cortex or trigeminal ganglion. The number of positive cells was not related to the volume of injectate but was related to the amount of injected blood. The density of cell labeling evoked by injecting mock cerebrospinal fluid or after catheter placement was markedly lower than after blood in all brainstem areas. The number of labeled cells was greatly reduced within trigeminal nuclear complex, parabrachial nucleus and medullary lateral reticular nucleus, but not within the nucleus of the solitary tract, area postrema or ependyma when blood was injected into adult animals in which unmyelinated C-fibers were destroyed by neonatal capsaicin treatment. Similar results were obtained after blood was instilled into the cisterna magna of rats in which meningeal afferents were chronically sectioned at the ethmoidal foramen bilaterally. We conclude that blood in the subarachnoid space is an effective stimulus for activating c-fos expression within subpopulations of brainstem neurons. Activation within trigeminal nucleus caudalis is mediated in large part by excitation of small-caliber meningeal afferents (trigeminovascular fibers), whereas c-fos expression within nucleus of the solitary tract and area postrema may reflect direct stimulation of blood or blood products, or possibly the response to autonomic activation from noxious stimulation.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1501770 TI - Persistent pain inhibits contralateral somatosensory cortical activity in humans. AB - To assess cortical activity during pain perception, regional cerebral blood flow (rCBF) studies were done in humans using single photon emission computed tomography (SPECT) with the radiotracer Tc99m-HMPAO and magnetic resonance imaging localization. Normalized SPECT data were analyzed by region of interest and change distribution. Contralateral somatosensory rCBF was decreased when the digits of the hand were immersed in a hot water bath for 3 min which was rated as moderately painful (persistent pain). No decrease was observed when the hand was immersed in tepid water (control). In contrast, cortical rCBF was increased during vibratory and sensorimotor tasks, in the contralateral somatosensory and sensorimotor areas, respectively. These results indicate that pain perception in man is associated with somatosensory cortical inhibition. PMID- 1501771 TI - Evidence for L-dopa systems responsible for cardiovascular control in the nucleus tractus solitarii of the rat. AB - Microinjections of L-DOPA (10-100 ng) into the medial area of the nucleus tractus solitarii (NTS) led to dose-dependent decreases in arterial blood pressure and heart rate in rats treated with i.p. 3-hydroxybenzylhydrazine, a central inhibitor of DOPA decarboxylase, or similarly with intraventricular 6 hydroxydopamine. D-DOPA, dopamine or noradrenaline (100 ng) produced no effect. L DOPA methyl ester (1 microgram), a competitive antagonist for L-DOPA, microinjected into NTS, blocked the depressor and bradycardic responses to L DOPA. High K+ (40 mM) released endogenous DOPA in a Ca(2+)-dependent manner from slices of the rat dorsomedial medulla including NTS. These results support the hypothesis that there exist systems of L-DOPA itself responsible for cardiovascular regulation in NTS of rats. This regulatory action of L-DOPA seems to be postsynaptic in nature. PMID- 1501772 TI - A neuropeptide Y (NPY)-related peptide is present in the river lamprey CNS. AB - Pancreatic polypeptide (PP)-like material from brain+spinal cord, and retina extracts of Lampetra fluviatilis was studied by HPLC and RIA. The brain+spinal cord extract showed a complex elution profile with multiple peaks of immunoreactivity. The retina extract showed a much simpler pattern with a single significant peak along with a trace of a second peak corresponding to the latest and penultimate peaks in the brain extract. Twenty-one out of 36 residues could be sequenced from the latest eluting peak in the brain extract. This sequence showed 81% identity with porcine neuropeptide (NPY) suggesting that both the brain/spinal cord and retina of the river lamprey contain a peptide homologous to NPY. PMID- 1501773 TI - Dendritic integration of motion information in visual interneurons of the blowfly. AB - Dendritic integration plays a key role in the way information is processed by nerve cells. The large motion-sensitive interneurons of the fly appear to be most appropriate for an investigation of this process. These cells are known to receive input from numerous local motion-sensitive elements and to control visually-guided optomotor responses (e.g., Trends Neurosci., 11 (1988) 351-358; Stavenga and Hardie, Facets of Vision, Springer, 1989). The retinotopic input organization of these cells allows for in vivo stimulation of selected parts of their dendritic tree with their natural excitatory and inhibitory synaptic input signals. By displaying motion in either the cells' preferred or null direction in different regions of the receptive field we found: (i) Responses to combinations of excitatory and inhibitory motion stimuli can be described as the sum of the two response components. (ii) Responses to combination of excitatory stimuli show saturation effects. The deviation from linear superposition depends on the distance and relative position of the activated synaptic sites on the dendrite and makes the responses almost insensitive to the number of activated input channels. (iii) The saturation level depends on different stimulus parameters, e.g. the velocity of the moving pattern. The cell still encodes velocity under conditions of spatial saturation. The results can be understood on the basis of passive dendritic integration of the signals of retinotopically organized local motion-detecting elements with opposite polarity. PMID- 1501775 TI - An electron microscopic study of neurosecretion in the cerebral ganglion of the earthworm. AB - Non-synaptic, exocytotic release of neurosecretory granules in cerebral ganglion neurons was observed electron microscopically in 3 species of the oligochaete annelids Aporrectodea caliginosa, Octolasion cyaneum and Lumbricus terrestris. In addition to the features indicating exocytotic release of neurosecretory granules into perineuronal space, possible features of neurosecretion into blood vessels were seen within the cerebral ganglion. Axon terminals in synaptic contact with perikaryal profiles of cerebral ganglion neurons were also found. PMID- 1501774 TI - Contribution of protein kinase C to central sensitization and persistent pain following tissue injury. AB - This paper provides evidence that central sensitization and persistent nociception following formalin-induced tissue injury in rats is dependent on the production of protein kinase C. Persistent nociceptive behavior in rats induced by subcutaneous formalin injection was significantly reduced by intrathecal pretreatment with a phospholipase C inhibitor (neomycin), and an inhibitor of protein kinase C (W-7), and was significantly enhanced by a phorbol ester (phorbol 12-myristate 13-acetate, PMA) and a stimulator of protein kinase C (SC 10). It is expected that noxious inputs associated with tissue injury produce a release of aspartate and glutamate within the spinal dorsal horn which by acting at ionotropic (NMDA) and metabotropic excitatory amino acid receptors produce an increase in intracellular messengers such as calcium and diacylglycerol which stimulate protein kinase C. PMID- 1501776 TI - Characterization of a glial associated antigen GA-1 by monoclonal antibody. AB - A glial antigen (GA-1) was identified by monoclonal antibodies (MAb) raised against C6 rat glioma cells. MAb-7D3 (IgG2a kappa) revealed GA-1 as a single protein band with a Rf value of 0.09 by the use of basic-PAGE Western blot. SDS PAGE Western blot and radioimmunoprecipitation (RIP) further resolved GA-1 into two subunits with a molecular weight of 200 and 78 kDa respectively. Subcellular localization by immunocytochemical staining revealed its cytosolic presence with a punctate pattern perinuclearly. Significant expression of GA-1 may be detected in 4 glioma or glial cell lines derived from rat brain. However, no expression may be detected in the rest of the 18 mammalian cell lines or primary neural cell cultures examined. All of the above data thereby suggest that GA-1 may be glial specific whereas the epitope of GA-1 defined by MAb-7D3 is species (rat) specific. PMID- 1501777 TI - Evidence that biocytin is taken up by axons. AB - Unexpected anterograde labeling is systematically observed in the pontine nuclei following iontophoretic injection of biocytin in the substantia nigra pars reticulata. Control experiments using WGA-HRP have led to deny the existence of a nigro-pontine pathway. The possibility that biocytin is taken up by fibers of passage has been tested. Deposits of biocytin in the corpus callosum result in a massive axonal labeling of this fibrous system. This study, in contrast to previous reports, stresses that biocytin is easily taken up and transported by axons. Hence, this tracer has to be used with careful controls when injected in structures crossed by fibrous tracts. PMID- 1501778 TI - Ultrastructural characterization of gonadotropin-releasing hormone (GnRH) immunoreactive terminal nerve cells in the dwarf gourami. AB - Recently we have been studying gonadotropin-releasing hormone (GnRH) cells of the terminal nerve (TN) in the dwarf gourami, which may serve as a good model system for the study of neuromodulator functions. Here we report on the ultrastructural characterization of TN-GnRH cells using postembedding immunoelectron microscopy. The GnRH immunoreactivities could be demonstrated on dense-cored vesicles (DCVs) in cell bodies, fibers and varicosities. However, we could find no evidence of GnRH-immunoreactive synapses which are characterized by active zones. This may suggest that GnRH is released non-synaptically from DCV-containing fiber varicosities and that it exerts its modulatory action on GnRH receptors located on nearby as well as distant target neurons. PMID- 1501779 TI - Reduction of NGF protein level in rat dorsal hippocampus following administration of kainic acid. AB - Intraperitoneal administration of kainic acid (KA) into adult rats caused a profound increase in nerve growth factor (NGF) mRNA and a significant reduction of NGF protein level in the hippocampus. Diazepam pretreatment suppressed both. The reduction of NGF level was apparent in the dorsal hippocampus at 2 h after KA administration, but a marked elevation of NGF protein was observed in the ventral hippocampus at 4 h. These results suggest that non-N-methyl-D-aspartate (NMDA) receptor agonists negatively influence NGF synthesis or stimulate NGF protein degradation in the dorsal hippocampus involving the CA1 sector. PMID- 1501780 TI - Increase of plasma neuropeptide Y-like immunoreactivity following chronic hypoxia in the rat. AB - In an attempt to understand the changes of circulating neuropeptide Y (NPY) during hypoxia, the plasma level of NPY was investigated by radioimmunoassay. Exposure of rats to hypobaric hypoxia at an altitude of 18,000 ft for 4 weeks causes an increase of pulmonary pressure and an elevation of plasma NPY-like immunoreactivity (NPY-LI). However, the systemic blood pressure was not elevated by this chronic hypoxia. Also, plasma noradrenaline (NA) estimated by chromatographic analysis (HPLC-ECD) was not markedly raised. Failure of bretylium and guanethidine, sympathetic neuron blockers, in reducing the plasma NPY-LI level of these rats ruled out the participation of adrenergic nervous terminals. Adrenal medulla seems responsible for this elevation of plasma NPY-LI because this magnitude disappeared in adrenalectomized rats. These data suggest that chronic hypoxia induced an elevation of circulating NPY from the adrenal gland of rats. PMID- 1501781 TI - Noradrenergic innervation of vasopressin-containing neurons in the rat hypothalamic supraoptic nucleus. AB - The noradrenergic innervation of vasopressin (VP)-containing neurons in the supraoptic nucleus (SON) of the rat hypothalamus was studied electron microscopically by using double-labeling immunocytochemistry combining the pre embedding peroxidase-anti-peroxidase method with post-embedding immunocolloidal gold staining. Noradrenaline-like immunoreactive axon terminals were found to make synaptic contacts with neurophysin II-like immunoreactive neurons in the SON. This provides morphological evidence for noradrenergic control of neuronal activity of VP-containing neurons at the SON level. PMID- 1501782 TI - Acute morphine induces oscillatory discharge of noradrenergic locus coeruleus neurons in the waking monkey. AB - Neurons were recorded extracellularly from the locus coeruleus (LC) of a waking, chair-restrained cynomolgus monkey before and for 0.5-4 h after intramuscular injections of morphine sulfate (0.3-10 mg/kg). Tonic discharge of each LC neuron tested (n = 11) decreased after morphine injection; this effect appeared to be dose-dependent for the range of 0.3-3.0 mg/kg. Unexpectedly, these same doses of morphine also induced a pronounced burst-pause discharge pattern in all LC neurons recorded. Thus, whereas in the naive animal pauses in discharge longer than 3 s were rare during waking, after morphine injection LC neurons frequently exhibited pauses in impulse activity of 10 s or longer during non-drowsy waking. The bursts in activity following morphine corresponded to orienting behaviors or apparent alertness, whereas pauses were associated with eye closure or slowly drifting gaze. Closer analysis revealed that this burst-pause activity pattern was somewhat regular, with a period of about 15-35 s. This observation was confirmed by autocorrelogram analysis. In view of previous findings in rodent LC, we suggest that acute morphine elicits a dual effect on primate LC neurons: inhibition of discharge by direct effects on opiate receptors located on LC cells, and periodic phasic activation mediated by excitatory afferents to the LC. PMID- 1501783 TI - Neuroprotective actions of riluzole in rodent models of global and focal cerebral ischaemia. AB - Riluzole (2 amino 6-trifluoromethoxybenzothiazole), when administered at 4 and 8 mg/kg i.p., 0.5, 4.5, 24 and 28 h after the initiation of ischaemia, significantly reduced the prevalence of slow wave, and increased the proportion of higher frequency activity seen in the quantified electrocorticogram (ECoG), during the weeks that followed a 6 min bilateral occlusion of the common carotid arteries in the Mongolian gerbil. In focal ischaemia, provoked in Fischer rats following the occlusion of the middle cerebral artery, administration of riluzole (8 mg/kg) at 30 min and 24.5 h post occlusion significantly reduced the volume of infarcted cortex. These activities of riluzole could be related to its inhibition of sodium channel activity, which in turn inhibits glutamate release. PMID- 1501784 TI - Time-dependent disruption of passive avoidance acquisition by post-training intra amygdala injection of tetrodotoxin in rats. AB - The role of the amygdala (AM) in the consolidation of the passive avoidance reaction (PAR) has been examined with the tetrodotoxin (TTX)-induced functional block of this structure. Rats were trained in the step-through PAR and anesthetized with ketamine. TTX injected immediately after acquisition into both AM (2 x 10 ng) significantly reduced avoidance of the dark compartment in the retrieval test performed two days later. The amnesic effect was significant when the acquisition--TTX delay was prolonged to 90 min but not to 6 h or 24 h. Earlier research indicated that TTX blockade of the parabrachial nuclei caused similar PAR disruption when elicited 24 h but not 48 h after acquisition. Comparison of the TTX-induced retrograde amnesias indicates that the two structures play different roles in the formation of the PAR engram. PMID- 1501785 TI - Muscarinic modulation of acetylcholine release from slices of guinea pig nucleus basalis magnocellularis. AB - Spontaneous and electrically evoked endogenous acetylcholine release and [3H] choline efflux from slices of guinea pig nucleus basalis magnocellularis (nbM) were studied. Tetrodotoxin reduced the spontaneous endogenous release by 55%, while the Ca(2+)-free medium reduced it by about 30%. Evoked [3H]-choline efflux was Na+ and Ca2+ dependent and frequency related. Physostigmine, 30 microM, nearly halved the stimulation-evoked efflux; atropine, 0.15 microM, not only antagonized, but even reversed this effect into facilitation. Pirenzepine, 1 microM, and AFDX 116, 1 microM, were less effective than atropine, and reversed the inhibitory effect of physostigmine only when applied together. 4-DAMP, 0.01 microM, was ineffective. These findings indicate that acetylcholine release in guinea pig nbM slices is inhibited by the cooperation of muscarinic autoreceptors, possibly belonging to the M1 and M2 subclasses. PMID- 1501786 TI - Event-related potentials in auditory backward recognition masking: a new way to study the neurophysiological basis of sensory memory in humans. AB - Task-irrelevant pairs of short tones were presented to healthy human subjects while electric potentials were recorded from their scalp ('event-related brain potential', ERP). Infrequent increments in the frequency of the first tone of the repetitive tone-pair elicited an extra ERP component termed 'mismatch negativity' (MMN) when the silent interval between the first and second tone of the pair ('inter-tone interval') was long (150, 300, or 400 ms) but not when this interval was short (20 or 50 ms). This effect did not depend on whether the two tones of the tone-pair were presented to the same or to different ears. The present inter tone interval effect is consistent with the effects of backward-masking on recognition performance in audition, suggesting that the MMN reflects the neurophysiological basis of echoic memory. PMID- 1501787 TI - Cortical and quasi-cortical regions innervate ventrostriopallidal structures in the rat: an electrophysiological analysis. AB - Antidromic unit driving was utilized to demonstrate afferent projections from prefrontal cortical (PFC) and quasi-cortical structures (main olfactory bulb, MOB; anterior olfactory nucleus, AON; basolateral amygdaloid nucleus, BLA) to the ventrostriopallidal region (VSPR) of the rat. In all regions explored, a substantial number of antidromically invaded neurons were found following electrical stimulation of the VSPR. In addition, both the AON and the amygdalostriatal zone harbor cells with branched axons which innervate the MOB and the VSPR and the agranular insular cortex and the VSPR, respectively. These results support and extend previous neuroanatomical and neurophysiological data on afferent connections of the VSPR and emphasize the fact that several regions of the basal forebrain, which are actively involved in processing of olfactory information, and the VSPR, are more closely interrelated than hitherto suspected. PMID- 1501788 TI - Noradrenergic-induced expression of c-fos in rat cortex: neuronal localization. AB - beta Adrenoceptors in the rat forebrain have been shown to exist predominantly on astrocytes. Studies were undertaken to determine whether the cellular localization of c-fos expression caused by the activation of brain beta receptors would have a similar cellular localization. Double label light and electron microscopic immunohistochemical experiments with a glial (glial fibrillary acidic protein, GFAP) and neuronal marker (neurofilament protein, NFP) were undertaken in rats treated with the adrenergic drug, yohimbine. These studies revealed a predominantly neuronal localization of Fos protein in the cerebral cortex. The latter results indicate that neurons are the postsynaptic noradrenergic target cells in which this immediate early gene is expressed in response to the stimulation of beta adrenoceptors. The possible relation of these findings to the glial localization of these receptors is discussed. PMID- 1501790 TI - Health-education workshops pay off for public and practitioners. PMID- 1501789 TI - Sleep-wake disorganization in cats exposed to ozone. AB - The effects of the exposure to ozone in the central nervous system are unknown, as it is doubtful if ozone enters beyond the respiratory tract. However, ozone exposure impairs human performance and induces subjective complaints such as fatigue, lethargy and headache. We studied electrographic aspects of sleep-wake organization in cats, and found that paradoxical sleep was promptly reduced during ozone exposure, followed by a dose-related increase of slow-wave sleep. These findings suggest that high concentrations of ozone or its reaction products induce striking changes in sleep patterns. PMID- 1501791 TI - NP shares experiences in ARNP Program. PMID- 1501792 TI - Syphilis: a review and update of this 'new' infection of the '90s. AB - Reported cases of primary, secondary and congenital syphilis are reaching epidemic proportions in the United States. Several factors have been associated with this increase, including budget reductions for syphilis-control programs, the growing use of cocaine among women of childbearing age and the practice of trading sex with multiple partners for illegal drugs. This article reviews the pathogenesis, clinical stages and presentation, serologic testing, treatment, and pertinent patient education for syphilis. Recommendations for the identification and prevention of syphilis are provided. PMID- 1501793 TI - AIDS dementia complex in the elderly. Diagnosis and management. AB - Ten percent of acquired immunodeficiency syndrome cases are reported in people 50 years of age or older. These older people have been infected with the human immunodeficiency virus primarily through homosexual contact, heterosexual contact or blood transfusion. AIDS in the elderly can be described as the new great imitator, often manifesting as an undetected dementia. This article focuses on the diagnosis and management of the AIDS dementia complex, a subcortical dementia with subtle and variable manifestations. The pathogenesis of AIDS dementia complex is not well understood; however, studies have shown that two-thirds of patients with AIDS exhibit overt dementia, and less than 10 percent of the brains of AIDS patients are found to be normal upon post-mortem examination. Clinical features of AIDS dementia complex include impairment in cognitive, motor and behavioral function. Since the primary care practitioner is the first line of defense in controlling the AIDS epidemic, including AIDS in the differential diagnosis for dementia is imperative. PMID- 1501794 TI - Canada's health care system provides lessons for NPs. AB - With increasing economic pressures, swaying public opinion and new government policies rationing health care resources, nurses in Canada are again challenging physicians for room to practice as nurse practitioners. Although the last Canadian nurse practitioner program was discontinued in 1983, and it was argued that the death of the role was inevitable in Canada's health care system, nurse practitioners have not vanished. Social plans in the United States are drawing heavily on the Canadian model of universal access and a government-funded health care system, and dramatic changes are taking place in Ontario's health care system. Now more than ever it is important that nurse practitioners understand Canada's health care system, why the NP role in Ontario has not been highly successful, and why the time is right for reintroduction of nurse practitioners into Ontario's health care system. PMID- 1501795 TI - Oral contraceptives still misunderstood. PMID- 1501796 TI - Nurse practitioner management of hospital-affiliated primary care centers. AB - Escalating health care costs have forced hospitals to develop alternative sources of revenue. Hospital-affiliated primary care centers that provide comprehensive health services to patients may also supplement hospital revenues with referrals for admission and/or special services. With their documented history of effectiveness, nurse practitioners are well-qualified to manage these primary care centers. This article provides guidelines to help nurse practitioners establish and manage a hospital-affiliated primary care center. Identification of clinical-services and staffing needs, and determination of office, administrative and facility requirements are also discussed. PMID- 1501797 TI - Hyperactive gag reflex linked to alcoholism. PMID- 1501798 TI - MCN outlines strategies for improving migrant health care. PMID- 1501799 TI - [Perinatology and nurse midwives. Divided opinions]. PMID- 1501800 TI - [Grading of the professional admission examination]. PMID- 1501801 TI - [Concerning ethics committees]. PMID- 1501802 TI - [Professional ethics. A universe to explore]. PMID- 1501803 TI - Discovering Jeanne Mance. PMID- 1501804 TI - [Moral choice. Its games and stakes]. PMID- 1501806 TI - [The new Civil Code Of Quebec: more respect for the person]. PMID- 1501805 TI - [The code of deontology. A useful but limited instrument]. PMID- 1501808 TI - [Ethics, rights and politics. Let's stake out shared ethical responsibilities]. PMID- 1501807 TI - [An ethical dilemma: reproductive rights for women infected with HIV]. PMID- 1501809 TI - [The acquisition of moral competences]. PMID- 1501810 TI - [Chronic obstructive pulmonary diseases. Elaboration of an ethical judgment]. PMID- 1501811 TI - Tuberculosis in New Zealand, 1985-90. AB - AIM: to examine recent trends in tuberculosis in New Zealand. METHODS: histologically and bacteriologically confirmed cases of tuberculosis notified to area health boards from 1985 to 1990 were analysed. RESULTS: a total of 843 cases were reported during 1985-90 for an average annual incidence rate of 4.2 cases per 100,000 population; incidence rates for each year were similar. The incidence of tuberculosis was higher among males than females and increased with age. Maori were five times more likely to develop tuberculosis than Europeans, Pacific Islanders were 10 times more likely, and persons of other ethnic groups combined were 15 times more likely. From 1985 to 1990, the number of cases decreased among Europeans, remained stable among Maori and Pacific Islanders, and increased among persons of other ethnic origin. CONCLUSION: although the overall incidence of tuberculosis is relatively low, it continues to be a public health problem in New Zealand, particularly among Maori and immigrants from Asia and the Pacific Islands. PMID- 1501813 TI - Jehovah's Witnesses and blood transfusion of infants. PMID- 1501812 TI - Primary malignant melanoma of skin in four regions of New Zealand. AB - AIMS: to describe the incidence and thickness of a representative collection of melanomas occurring in recent years in New Zealand. METHODS: all pathology reports of primary malignant melanoma of the skin, in defined periods in 1987-9, were collated for four regions of New Zealand. RESULTS: nonMaori incidence rates were 52 and 58 melanomas per 100,000 person years for men and women, respectively. These rates are much higher than the 24 per 100,000 person years for melanoma registrations in 1983-4. The age standardised invasive melanoma rate of 35 per 100,000 person years was higher than those of most Australian states and close to the rate for Queensland in 1986. Preinvasive melanomas comprised 26% of all melanomas. Of invasive melanomas, 58% in men and 55% in women were less than 0.76 mm in thickness; 7% of invasive melanomas in men and 5% in women were at least 3.5 mm thick. CONCLUSIONS: increasingly early detection of malignant melanomas in successive years is likely to have contributed to the recent increase in incidence, perhaps to a major degree, but an environmental cause cannot be excluded. PMID- 1501814 TI - Taking an infant's temperature: axillary or rectal thermometer? AB - AIM: to examine the validity of routine use of axillary thermometers to measure body temperature in infants. METHODS: comparison of 49 simultaneous paired axillary and rectal temperature recordings in infants between one and 11 months of age, who were considered afebrile by their clinicians. Regression analysis of the paired measurements, and a plot of the differences between the paired measurements against their means, were used to examine the limits of agreement of the two methods. RESULTS: the limits of agreement ranged from 0.2 to 1.6 degrees C difference between simultaneous paired measurements. As there was no consistent relationship between axillary and rectal temperatures, the use of a correction factor added to axillary values is invalid. The axillary thermometer may record almost the same as the rectal temperature or more than 1.5 degrees C lower at the same point in time. CONCLUSION: we question the validity of current clinical practice in assessing infant body temperature by using axillary thermometers, and we suggest that such measurement does not reflect the rectal temperature in a reliable or consistent fashion. If infant body temperature is sought, a rectal thermometer should be used. PMID- 1501815 TI - The difficulties and costs of ethical assessment of a national research project. AB - In 1990 we applied to the 14 area health board ethical committees for approval of a national study of childhood cancer. All the committees approved the study, but the process was time consuming and costly. The times taken for the committees to grant approval, ranged from two to 36 weeks. The committees had differing requirements. We recommend that a single ethical committee should take responsibility for dealing with each multicentre study in New Zealand. This would ensure uniformity of approach, and minimise delays and costs. PMID- 1501816 TI - Diabetes--inpatient utilisation, costs and data validity. Dunedin 1985-9. AB - AIM: to describe the impact of diabetes on the public hospital inpatient services in one New Zealand region over the period 1985-9, from one 450 bedded university teaching hospital in a major urban centre in New Zealand serving a population of approximately 125,000 people. METHODS: by the analysis of routinely collected hospital discharge data and the application thereto of the resource utilisation system (RUS). Data validation was performed by means of a survey of clinical notes. RESULTS: admission, bed utilisation rates and associated costs for diabetes rose over the period by factors of 3.2, 3.8 and 2.8 respectively; due primarily to the management of macrovascular disease in the elderly. The rise was most marked in those 75 years and over; admission rates, bed utilisation rates and costs in this age group being respectively 1.9, 4.3 and 2.9 times greater than the 60 to 74 year age group. For admissions with diabetes as principal diagnosis, admissions for glycaemic control showed a significant decrease in lengths of stay over the period. Admissions with diabetic peripheral vascular disease were cumulatively, and per case, the most costly, the mean cost, at $16,000 per case, being 5.1 times greater than the mean cost of all admissions with diabetes as principal diagnosis. In 1989 diabetes accounted for 5% of the cost of all inpatient care provided by the hospital. These results are an underestimate, as 45% of admissions of people where diabetes should have been cited as a subsidiary diagnosis were omitted from the discharge data. CONCLUSION: diabetes is a major consumer of hospital resources in this region. As the majority of diabetes associated resource use is in the elderly, a population projected to increase significantly, consideration needs to be given to the options for the provision of care. More work also needs to be done on the reasons underlying these changes. If routinely collected data is to be used for these purposes then audit of the data must be performed or use should be restricted to certain defined groups, eg, diabetes as principal diagnosis only. PMID- 1501817 TI - Travel associated illness. PMID- 1501818 TI - Cot death. PMID- 1501819 TI - Immunisation in the Nelson area. PMID- 1501820 TI - Screening for noninsulin dependent diabetes mellitus. PMID- 1501821 TI - Fetal echocardiography. PMID- 1501822 TI - X-linked muscular dystrophy--phenotypic/genotypic correlation. PMID- 1501823 TI - Details please... PMID- 1501824 TI - New grads' goals not clear yet. PMID- 1501825 TI - Reflections of a new nurse manager. PMID- 1501826 TI - Labor liability--recruiting and hiring. PMID- 1501828 TI - When the system fails. PMID- 1501827 TI - Community nursing centers coming of age. PMID- 1501829 TI - Informatics: nursing's newest specialty. PMID- 1501830 TI - Patient needs drive an integrated approach to care. PMID- 1501831 TI - Whole brain thinking and the nurse manager. PMID- 1501832 TI - Making performance appraisals a positive experience. PMID- 1501833 TI - Nursing ethics committees: the time is now. PMID- 1501834 TI - Nine budget-conscious strategies for education. PMID- 1501835 TI - New graduates: what does my manager expect? PMID- 1501836 TI - The child care business: should hospitals invest? PMID- 1501837 TI - Recollections of a pioneering venture. PMID- 1501838 TI - 12 commandments to communication in a decentralized system. PMID- 1501839 TI - Education: growing our own nurses. PMID- 1501840 TI - Successful downsizing. PMID- 1501841 TI - Day of renewal. PMID- 1501842 TI - Using simulation to project staffing levels. PMID- 1501843 TI - Empowerment: charting for retention. PMID- 1501844 TI - "Operation Information" for ambulatory surgical patients. PMID- 1501845 TI - Establishing a women's center. PMID- 1501846 TI - A student mentor award. PMID- 1501847 TI - Outreach: prostatic cancer screening. PMID- 1501848 TI - Executive stress: an ounce of prevention... PMID- 1501849 TI - Advanced licensure: personal plum or public shield? PMID- 1501850 TI - [Surgical implications of chronic liver diseases]. AB - Complications of chronic liver diseases requiring surgical interventions are the following: esophageal varices and bleeding, ascites hypersplenism, some forms of liver insufficiency. The most widely accepted method for treatment of esophageal varices is endoscopic sclerotherapy. Portal systemic shunts are indicated in some cases. Intractable ascites is to be treated by peritoneovenous shunt insertion. "Ressissance" of paracentesis is not confirmed by late results. Splenectomy is proposed if clinical signs are prominent. If portal hypertension exists, shunt should be performed simultaneously. Liver transplantation is indicated in cases of irreversible liver damage. Optimal selection of patients and timing of transplantation remains of critical importance. As a consequence of numerous technical modifications liver transplantation becomes more popular. Statistical data on liver diseases in Hungary call for urgent development of hepatology. Cooperation of physicians is of outmost importance to realize it. PMID- 1501851 TI - [Obstructive ectopic ureterocele: review of the literature in the light of the authors' own experience]. AB - The epidemiology, clinical presentation, evaluation and methods of surgical management of ectopic ureteroceles was studied. The prenatal detection of hydronephrosis of the upper pole of duplex systems allows early surgical correction, and this effectively decreases the risk of urinary tract infection, urosepsis and irreversible loss of renal function. Yet a precise prenatal diagnosis of accompanying ureterocele is not necessary for efficient postnatal management. PMID- 1501852 TI - [Cellular DNA determination and its significance in the identification of tumor recurrences, metastases and second primary tumors]. AB - The DNA content of 30 malignant tumors and their metastases were compared. The DNA indices of tumors (expressed by the mean DNA content of G0.1-phase tumor cells and leukocytes) differ from each other, but in metastases they are almost the same with the values of primary tumors. It can also be observed, if a tumor consisted of more than one subpopulation of tumor cells, the metastatic potential of clones can be different. However, there is no significant relationship between the degree of ploidy and the occurrence of metastasis. The stability of DNA index in tumors and their metastases were used to distinguish two primary tumors even if their histological patterns were very similar. We present an example of the above mentioned phenomena in which the results of DNA analysis is supported by the results of mucin histochemistry and the follow up data. PMID- 1501853 TI - [Newest method for the detection of chronic intestinal ischemia: color Doppler sonography]. AB - Authors describe the case of a patient with chronic abdominal pain due to the occlusion of the superior mesenteric and the significant stenosis of the inferior mesenteric artery, discovered by color-Doppler ultrasonography. The role of this new non-invasive method in the diagnose of chronic intestinal ischaemia is emphasized. It seems to be suitable for the replacement of angiography also in the postoperative period. PMID- 1501854 TI - [Collagen sprue--a rare form of adult celiac disease]. AB - The authors report the first case of collagenous sprue in Hungary. This condition is characterized by coeliac type small bowel malabsorption, resistant to gluten free diet and other therapeutic efforts, associated with poor prognosis. The diagnosis depends on the histological demonstration of extensive collagenization of the lamina propria in the flat jejunal mucosa. This disease must be kept in mind at differential diagnosis of chronic diarrhoea with progressive malabsorption, especially if it is resistant to gluten withdrawal than conventional coeliac disease. PMID- 1501855 TI - [Hepatology at the middle of the past century: contemporary Hungarian review of Frerichs' book]. PMID- 1501856 TI - [The dismal 125 days of the Royal Hungarian University Battalion relocated to Germany at the end of 1944]. PMID- 1501857 TI - [External irradiation of differentiated thyroid cancer: 30 follow up]. AB - Following surgery which left no macroscopic residue 114 patients with differentiated thyroid cancer (58 papillary, 56 follicular) were subgrouped on the basis of the dose of prophylactic postoperative external radiation applied: group I--an adequate dose of radiation (greater than or equal to 4500 cGy of telecobalt, greater than or equal to 4000 R of orthovolt therapy); group II--an inadequate dose of radiation (including non-irradiated patients). Local/regional relapse-free survival (LRRFS), distant metastatic relapse-free survival (DMRFS) and total cause-specific survival (TCSS) were calculated by means of life-table analysis for both histologic types separately. Results. 1. TCSS and LRRFS were significantly (p less than 0.001) better for group I in papillary cancer. No difference was found in DMRFS. 2. LRRFS was significantly (p less than 0.001) better for group I in follicular cancer. No differences were found in TCSS and DMRFS. CONCLUSIONS: 1. The prophylactic postoperative external irradiation is an effective method for survival prolongation in papillary cancer, the local/regional recurrences thereby being reduced. 2. External irradiation, in conjunction with radioiodine treatment, should be considered in the postoperative management of follicular cancer to diminish local/regional relapse. PMID- 1501858 TI - [Barrett esophagus]. AB - There are a lot of contradiction and uncertainty related to Barrett's esophagus. Authors review the literature about the incidence, the aetiology, the pathology of the ailment, the possibility of diagnosis and treatment. 25 Barrett's esophagus were observed in the course of controlling of patients after antireflux operations and investigations of patients suffering from gastroesophageal reflux disease. X-ray examination, endoscopy, biopsy, 24-hour pH monitoring of the distal esophagus and esophageal manometry were performed. Because of the possibility of malignant transformation Barrett's esophagus requires yearly endoscopic surveillance and biopsy at least. Antireflux procedure does not protect against the development of adenocarcinoma. PMID- 1501859 TI - [Comparison of human milk with 3 different types of infant food in the nutrition of full-term neonates]. AB - Healthy, term infants who were either breast-fed, or received conventional formula (Mildibe, EGIS; Pre-Aptamil, Milupa), or a formula containing hydrolyzed proteins (Aptamil H. A., Milupa) were investigated. Each group consisted of 10 infants who were fed ad libitum. Somatic development (gain in weight, length and head- and chest circumferences), serum Ca and P levels, alkaline phosphatase activities and basic biochemical parameters of protein metabolism (serum total protein, albumin, uric acid, creatinine and urea nitrogen levels) were determined at the ages of 2, 4 and 8 weeks. Anthropometric measurements did not reveal considerable differences between the groups investigated. At the age of four weeks, serum calcium levels were significantly higher in the breast-fed infants than in those receiving formula. Both at the ages of four and eight weeks, serum total protein levels were significantly lower in the infants receiving the formula consisting of hydrolyzed proteins than in the breast-fed controls. No difference of considerable extent was seen in the other biochemical parameters measured. The results obtained indicate that, in the lack of the possibility of breast-feeding, all the three formulae investigated can be used as substitute of breast milk. PMID- 1501860 TI - [Experience with the Direx Tripter X-1]. AB - In nonselected patients 81.5% stone-free rate could be reached in 3 months. In authors's opinion Direx Tripter X-1 is suitable in the treatment of renal and ureteral calculi. They treated staghorn calculi by ESWL monotherapy with success. The Direx lithotripter was found to be effective and easy to operate; the potential cost reduction is of great significance. The treatment requires general anaesthesia and the equipment causes significant noise. After all, Direx lithotripter is a useful machine in the armamentarium of stone disease treatment. PMID- 1501861 TI - [Primary neonatal liver cyst]. AB - The authors found with neonatal ultrasound screening a cyst in the epigastrium sized 45 x 18 x 36 mm. The newborn was operated at age of 7 days. The cyst was in the right lobe of the liver and after extirpation healed. PMID- 1501862 TI - [Comparison of ST depression and various exercise test indices in the diagnosis of coronary stenosis]. AB - Various modifications and refinements have been proposed to improve the diagnostic accuracy of standard ST-segment criteria for identifying coronary artery disease using exercise testing. To ascertain if the treadmill exercise score (TES), the ST integral, or the ST/HR index are significantly better markers for coronary disease the standard ST analysis, measured visually or by computer, a retrospective study of 173 male patients was performed. Exclusions were clinical or electrocardiographic evidence of prior myocardial infarction, left ventricular hypertrophy, left bundle branch block, or resting ST segment depression on their baseline electrocardiogram, digitalis, previous revascularization procedure or any significant valvular or congenital heart disease. Ninety-six patients (55.5%) had at least one epicardial coronary stenosis (more than 70% diameter stenosis). Cutpoints were chosen for each method, that maximized their best combination of sensitivity and specificity. There were no statistically significant differences between any of the five methods (TES, ST integral, ST/HR index, standard and computer ST analysis) for identifying any coronary disease. CONCLUSION: careful visual or ST-segment analysis continues to be the simplest as well most effective marker for coronary disease during exercise testing. PMID- 1501863 TI - [A new method for the classification of neonates based on maturity and somatic development]. AB - The author points out the sad fact that the methods of estimating classifying, comparative examining of the maturity, somatic development of newborns and the methods of marking off the retarded newborns used up to now are essentially centering round the birth-weight. He exposes the errors, deficiencies of these methods and confronts them with the possibilities of the NDN-system (newborn's somatic development and nutritional state) worked out earlier by him. He thinks the NDF-system to be able to express simultaneously and exactly the gestational age, weight- and length-development, state of being fed of the newborns and the relation to the populational average, the fact and type of retardation, as well. The informational means of NDF-system in NDF-index. The NDF-system makes it possible to break down the birth-weight centric view as it offers a more suitable and qualified method than used before to describe the maturity and somatic development and the classifying of the newborns on the basis of these. PMID- 1501864 TI - [Practical questions concerning the laboratory diagnosis of monoclonal immunoglobulin A (IgA)]. AB - Authors discuss about the laboratory determination and differential diagnostic problems of the homogenous and heterogenous immunoglobulin increases--in respect to the monoclonal IgA--in the serum and urine. Their investigating system is convenient for the early detection of the small M-components and to discover the other rare protein anomalies too. PMID- 1501865 TI - [Reasec poisoning in childhood]. AB - Three cases of severe accidental poisoning with "Reasec" in infants and young children are reported. Patients' medical history, the clinical features and ways of antidote administration are described. In severe poisoning in addition to symptomatic intensive care administration of "Narcanti" in continuous infusion is recommended. The necessity of strict observation and ventilation facilities because of the potential respiratory failure is emphasised. PMID- 1501866 TI - [Successful electroconvulsive treatment of a schizophrenic patient suffering from severe hemophilia A]. AB - Experiences obtained with the electroconvulsive treatment of a schizophrenic patient suffering from severe haemophilia A are reported. No haemorrhagic complications were observed. According to our experiences electroconvulsive therapy can be applied also in severe haemophilia A if satisfactory replacement therapy can be ensured. Similar case has not been found in the literature. PMID- 1501867 TI - [A case of Lyme carditis]. AB - The authors introduce their patient suffering from Lyme carditis. This causes III. degree AV block, then spontaneous remission, and complete recovery. Depending on the bases of other scientists' works they introduce their experiences in the clinic and therapy of the disease. PMID- 1501868 TI - [Analysis of human growth hormone-binding protein in plasma by high pressure liquid chromatography]. AB - A technique using high pressure liquid chromatography gel filtration was used to evaluate GH-binding proteins (GH-BPs) in human plasma; eluate was monitored for radioactivity in a gamma-detection system connected to a computer. Plasma (200 microliters) was incubated with 125I-human (h) GH (200,000 cpm) at 4 degrees C for 20 hours. Our GH binding assay offers important gains in terms of rapidity and resolution; it has permitted a clear separation and characterization of the two GH-binding components present in human plasma. PMID- 1501869 TI - [Economic aspects of roentgen film. Expert opinions, proposals]. PMID- 1501870 TI - [Family medical care and laboratory diagnosis]. PMID- 1501871 TI - [The intrauterine contraceptive device]. PMID- 1501872 TI - [Olfactory inhibitor effect of gentamycin nose drops]. PMID- 1501873 TI - [Position of the Hungarian Society of Family Physicians on the introduction of a new family physician system]. PMID- 1501874 TI - [Backwards of forwards?]. PMID- 1501875 TI - [Abnormal eating behavior in children. "I will not eat my soup ...!]. PMID- 1501876 TI - [Child abuse]. PMID- 1501877 TI - [Child oncology]. PMID- 1501878 TI - [Diplomated pediatric and infant nurse in extramural nursing]. PMID- 1501879 TI - [A man and many babies]. PMID- 1501880 TI - [Discharge information for maternity patients]. PMID- 1501881 TI - Biochemical properties of the growth suppressor/oncoprotein p53. AB - The cellular p53 protein is so called because of its molecular weight as determined by SDS-polyacrylamide gel electrophoresis. It was originally classified as a nuclear oncogene product when it was shown by DNA transfection experiments that p53 is able to extend the lifespan of primary rodent cell cultures and to cooperate with an activated ras oncogene to achieve complete transformation of primary cells. However, there is now conclusive evidence that loss of normal p53 expression may be an important step in cell transformation and tumorigenesis. Furthermore, it has been shown that mutant p53 was used for the experiments demonstrating the immortalizing and transforming capacity of p53. Wild-type p53 seems to negatively regulate cell growth and division. So far, the basic function of p53 is not known. Biochemical variability seems to be a key feature of p53 and an understanding of biochemical variations in the p53 protein may contribute to an understanding of how p53 is regulated or how p53 may regulate cell proliferation. Thus, the present review will focus on the biochemical properties of p53. PMID- 1501882 TI - The functional domain of the stimulatory GDP/GTP exchange protein (smg GDS) which interacts with the C-terminal geranylgeranylated region of rap1/Krev-1/smg p21. AB - rap1/Krev-1/smg p21 (smg p21), a member of the small GTP-binding protein (G protein) superfamily, has a geranylgeranylated cysteine residue and clustered basic amino acids in the C-terminal region. The GDP/GTP exchange reaction of smg p21 is regulated by smg GDS, which is also active on Ki-ras p21 and rho p21. The C-terminal region of smg p21 is essential for its interaction with smg GDS. Moreover, smg p21 is phosphorylated by cyclic AMP- and cyclic GMP-dependent protein kinases at the serine residue between the polybasic region and the prenylated cysteine residue, and this phosphorylation initiates the smg GDS induced smg p21 activation. Thus, the C-terminal cationic and hydrophobic region is important for the regulation of the smg p21 activity. In the present study, we attempted to determine the functional domain of smg GDS which interacts with the C-terminal region of smg p21 by use of a cross-link method and a site-directed mutagenesis method. The region of smg GDS cross-linked with the C-terminal region of smg p21B was residues 444-492, which is located at the C-terminal fifth of smg GDS. On deletion of these residues, smg GDS became inactive on smg p21B, Ki-ras p21 and rhoA p21. These results indicate that residues 444-492 of smg GDS are at least one of the domains which interact with the C-terminal region of its substrate small G proteins. PMID- 1501883 TI - Genomic dispersal of the ets gene family during metazoan evolution. AB - Evolutionary homologs of the ets proto-oncogene have been discovered in the genomes of widely divergent eucaryote species from Drosophila to sea urchin to vertebrates. The prototype mammalian ets-1 and ets-2 genes are divided into three coding domains that differ in their rate of accumulation of sequence divergence. An analysis of sequence divergence of ets gene homologs in various species has produced a phylogenetic history of the ets gene family in the context of metazoan evolutionary radiation. A minimum of five duplication events of ets primordial genes were evident, namely (1) a duplication that separates primitive ets genes (Drosophila precursor of 74E, mouse PU.1 and human ELK1) from the ets-1, ets-2, erg ancestor; (2) and (3) two duplications that established separate ets, erg and elg/GABP-alpha lineages which occurred prior to invertebrate-vertebrate divergence; (4) divergence of ets-1 and ets-2 gene family also associated with vertebrate-invertebrate divergence; (5) duplication of ets-1 and ets-2 in Xenopus laevis to produce two ets-1 genes and two ets-2 genes during genomic tetraploidation in the recent ancestry of this species. PMID- 1501884 TI - Mapping of UV photoproducts within ras proto-oncogenes in UV-irradiated cells: correlation with mutations in human skin cancer. AB - Mutations in ras proto-oncogenes have been found in human skin cancers. Since ultraviolet light is implicated in the development of skin cancers, we have investigated the formation of UV-induced photoproducts along exons 1 and 2 of the three ras proto-oncogenes, H-ras, K-ras, and N-ras, in UV-irradiated human cells. The two major types of DNA photoproducts, cyclobutane pyrimidine dimers and pyrimidine (6-4) pyrimidone photoproducts [(6-4) photoproducts], were mapped at the DNA sequence level by ligation-mediated polymerase chain reaction (LMPCR). No significant differences were seen between irradiated purified DNA and irradiated cells, implying that local chromatin structure does not influence the distribution of photoproducts along exons 1 and 2 of the three ras genes. We find that the transcribed strand near codon 61 in H-ras, K-ras and N-ras shows a high frequency of potentially mutagenic cyclobutane dimers and (6-4) photoproducts. Codon 12 of H-ras, K-ras and N-ras displays only barely detectable photoproducts at a CpC dinucleotide. In human skin cancers, mutations were most frequently detected at codon 12 of H-ras and K-ras. These results imply that the initial frequency distribution of a mutagenic DNA adduct may not correlate with mutation spectra in human tumors. PMID- 1501885 TI - Transcriptional activator Tax of HTLV-1 binds to the NF-kappa B precursor p105. AB - Human T-cell leukemia virus type 1 (HTLV-1) induces adult T-cell leukemia and also a neurological disease, tropical spastic paraparesis. Tax protein (p40tax) of HTLV-1 activates in trans its own transcriptional enhancer in the long terminal repeat and also those in some cellular genes such as interleukin 2 receptor alpha, granulocyte-macrophage colony-stimulating factor, Fos, Jun and MHC class I. Thus, Tax has been proposed to play a critical role in the pathogenesis induced by HTLV-1 infection. Here, we report formation of a complex of Tax protein with the precursor protein p105 of the NF-kappa B p50 subunit. p105 was co-immunoprecipitated with Tax protein from cells infected with HTLV-1 from cells transfected with the Tax expression plasmid, but not from cells transfected with inactive mutants of Tax. Furthermore, a GST-p105 fusion protein produced in Escherichia coli bound to Tax protein. These results strongly suggest that the trans-activator Tax protein forms a complex with precursor NF-kappa B p105 and plays a role in trans-activation of transcriptional initiation. PMID- 1501886 TI - Functional analysis of the N-terminal domain of Tat protein of the human immunodeficiency virus type 1. AB - The Tat protein of human immunodeficiency virus type 1 (HIV-1) is a potent trans activator of the viral long terminal repeat (LTR). The N-terminal region of Tat is rich in proline and acidic residues analogous to the activation domains of other transcription factors such as GAL-4 and CTF/NF-1. Several basic residues are also present in this region. To investigate the role of these structural features in the Tat-mediated trans-activation, we have chemically synthesized and evaluated Tat analogs with alanine or glutamine replacing one or more of these amino acid residues. Our data show that substitution of Glu-2, His-13, or all the proline in the Pro-Xaa3-Pro triad drastically reduced activity. In contrast, changes at Arg-7, Lys-12 and any one proline residue in the triad moderately reduced, and substitution of Lys-19 showed little effect on, activity. These results show that the native structure of the N-terminal 19 amino acid sequence is essential for Tat function, and that the overall topology of this domain and not the acidic residues alone appears necessary for trans-activation. PMID- 1501887 TI - Activation of interleukin-2 receptor alpha expression by extracellular HTLV-I Tax1 protein: a potential role in HTLV-I pathogenesis. AB - The Tax1 protein of human T cell leukemia/lymphoma virus type I (HTLV-I) has been shown to stimulate the proliferation of human lymphocytes. Here we report that lymphocyte proliferation can be induced at extracellular Tax1 concentrations as low as 25 pM. The proliferative response induced by extracellular Tax1 is accompanied by an activation of endogenous interleukin-2 receptor alpha-chain (IL 2R alpha) expression in human lymphocytes. Functional activation of IL-2R alpha expression in peripheral blood lymphocytes treated with Tax1 was demonstrated using an [125I]IL-2-binding assay. In addition, an enzyme-linked immunosorbent assay demonstrated that soluble IL-2R alpha in the medium of IL-2- and Tax1 treated cells was over 13-fold greater than in the medium of control treated cells. Overexpression of IL-2R alpha is a common clinical feature of some patients with adult T-cell leukemia (ATL) and tropical spastic paraparesis/HTLV-I associated myopathy (TSP/HAM). The ability of extracellular Tax1 protein to activate expression of IL-2R alpha in both infected and uninfected lymphocytes may contribute to the abnormal lymphocyte proliferation observed in both ATL and TSP/HAM. PMID- 1501888 TI - Max and c-Myc/Max DNA-binding activities in cell extracts. AB - We have examined the interactions and DNA-binding activities of the c-Myc oncoprotein and its partner Max. In cell extracts virtually all c-Myc molecules are associated with Max in heterodimeric complexes. Moreover, DNA-binding studies with in vitro-translated protein and cell extracts show that both Max alone and c Myc/Max bind the same DNA sequence. Conversely, c-Myc is unable to bind this sequence in the absence of Max. These findings suggest that c-Myc may function via obligate complex formation with Max. PMID- 1501889 TI - Rapid, complete and reversible transformation by v-sis precedes irreversible transformation. AB - v-sis is the oncogene of simian sarcoma virus, but whether tumor growth is maintained by v-sis expression alone or requires additional changes is unknown. To distinguish these possibilities we studied a model of reversible transformation including tumorigenicity using NIH3T3 cells bearing a metallothionein promoter-v-sis construction. Cells subcultured from 10 out of 18 tumors from athymic mice, all less than 0.1 g and less than or equal to 21 days in age, reverted to a normal phenotype but exhibited transformation upon addition of zinc as judged by morphology, growth rate, saturation density and anchorage independence of growth. Thus, activation of v-sis alone is sufficient for initiation and early autocrine-based growth of tumors. However, the cells from the remaining and predominantly larger, 0.5 +/- 0.7 g, tumors did not revert and exhibited zinc-independent transformation as judged by the same criteria. Southern analysis and examination of the regulation of v-sis product expression in cells derived from these tumors showed no change in zinc-dependent and reversible regulation of v-sis sequences. These results suggest that subsequent tumor growth strongly favors acquisition of additional irreversible change(s) in the tumor cell genome at high frequency (44%). Thus an early event of a multistep process stimulated by v-sis-dependent transformation best accounts for the sum of results. PMID- 1501890 TI - The binding of transcription factor Sp1 to multiple sites is required for maximal expression from the rat transforming growth factor alpha promoter. AB - Transcription from the rat transforming growth factor alpha (TGF-alpha) promoter initiates at multiple sites within a 200-bp G+C-rich region that lacks TATA and CAAT motifs but contains multiple potential binding sites for the transcription factor Sp1. In the present study, we used deletion analysis to establish the 5' boundary of sequences required for efficient transcription from the predominant 58 start site. We then examined the functional activity of several putative Sp1 binding sites that occur within the transcriptionally important region downstream from -155. In the presence of either crude HeLa cell extract or purified Sp1 protein, two double-stranded oligonucleotides from this region, each of which contains three Sp1 elements, both displayed gel mobility shifts that were specifically inhibited in the presence of excess bona fide Sp1-binding sequence from the hamster dihydrofolate reductase (DHFR) gene. Methylation interference analysis of the major gel-shift complex produced with one of these oligonucleotides revealed a series of critical guanine residues located in, or adjacent to, one of the putative Sp1 recognition elements. The functional importance of Sp1 binding was confirmed by the findings that transcription in vitro from the -58 start site was inhibited in the presence of excess consensus Sp1-binding sequence and that coexpression of Sp1 dramatically induced TGF-alpha promoter-directed chloramphenicol acetyl transferase (CAT) expression in transfected Drosophila Schneider cells that otherwise lack functional Sp1. Additionally, the introduction of mutations into any of several putative Sp1 elements inhibited transcription in vitro from the -58 site, with the most proximal element tested having the largest effect. Sequential mutation of more distal elements produced a synergistic inhibition of transcription, suggesting that cooperative interactions between Sp1 sites are necessary for full expression from the TGF-alpha promoter. PMID- 1501891 TI - Constitutive expression of exogenous myc in myelomonocytic cells: acquisition of a more transformed phenotype and inhibition of differentiation induction. AB - The effects of deregulated expression of the human c-myc and MC29 v-myc oncogenes have been examined in a murine myelomonocytic cell line J774 (c-myc) and in a variety of myelomonocytic cell lines of different degrees of maturity generated from primary hematopoietic tissue (v-myc). Introduction of a Moloney murine leukemia virus long terminal repeat (LTR) c-myc construct into J774 cells resulted in constitutive expression of the exogenous myc gene and a concomitant increase in the degree of transformation and tumorigenicity of the cells. In addition, constitutive expression of exogenous myc inhibited induced differentiation of these cells by a variety of treatments including addition to the medium of lipopolysaccharide (LPS) or the phorbol ester 12-O-tetradecanoyl phorbol 13-acetate (TPA) as well as complete withdrawal of serum from the medium. The degree of increased transformation, tumorigenicity and inhibition of terminal differentiation was dependent upon the level of exogenous myc expression. For the v-myc-generated myelomonocytic cell lines, introduction of v-myc resulted in a high degree of transformation and, irrespective of the differentiation status of the cells, a block of induced differentiation. These results indicate that the level of constitutive myc expression can affect the transformed phenotype, tumorigenicity and differentiation inducibility of myelomonocytic cells. PMID- 1501892 TI - In vivo footprints between the murine c-myc P1 and P2 promoters. AB - Assuming that when transcription starts at the P2 promoter of the c-myc gene sites located immediately upstream from P2 are occupied whereas in the absence of initiation they are not, the polymerase chain reaction (PCR)-based method of Mueller & Wold [(1989). Science, 246, 780-786] was used to map in vivo footprints upstream from the P2 promoter in various mouse cell lines. In cultured Friend erythroleukemic cells induced to differentiate with dimethysulfoxide (DMSO), a clear protection corresponding to ME1a2 and E2F sites was observed, consistent with in vitro band-shift and footprint data. However, in cell lines in which the gene was either silent or truncated the footprints were no longer visible. Friend c-myc transcripts decreased to a barely detectable level after 3 h of DMSO treatment. Transcription, as measured by in vitro run-on, was turned off at the level of RNA polymerase elongation rather than initiation [Mechti N., Piechaczyk, M. Blanchard, J.-M., Marty, L., Bonnieu, A., Jeanteur, Ph. & Lebler, B. (1986). Nucleic Acids Res., 24, 9653-9666]. The state of occupancy of the sites did not vary from the first hours up to 9 days of DMSO treatment, suggesting that DNA occupancy per se cannot explain premature termination, which rather would involve a more complex phenomenon. PMID- 1501893 TI - Expression of the normal p53 gene induces differentiation of K562 cells. AB - The multistep nature of human cancers is well illustrated by chronic myelogenous leukemia (CML), a clonal hematologic malignancy with two distinct phases: chronic and acute. Transition between these phases is characterized by unregulated growth and loss of differentiation of myeloid cells and their progenitors. We recently reported that loss of normal p53 expression correlates with transition from the chronic to acute phase in at least 25% of cases of CML. However, the precise relationship between this loss and biologic features of acute-phase CML is uncertain. To study this question, we artificially expressed normal p53 in K562, an erythroid acute-phase CML cell line lacking normal p53 expression. Biological effects were assessed by determining several growth parameters and by measuring synthesis of hemoglobin, a feature of mature erythroid cells. K562 cells expressing normal p53 had an increased proportion of cells in G1 versus S + G2, a longer doubling time and a lower growth saturation density than control K562 cells or K562 cells with antisense p53. Cells with normal p53 also expressed up to 50-fold more hemoglobin than controls. These data are consistent with the notion that loss of p53 expression may be responsible for many of the features of acute-phase CML cells. The data also demonstrate direct involvement of p53 in differentiation processes. PMID- 1501894 TI - Lack of expression of tumor-suppressor genes in human malignant glioma cell lines. AB - Human malignant gliomas (glioblastomas and anaplastic astrocytomas) are the most frequent brain tumors and are associated with a variety of genetic alterations including retinoblastoma (RB) and p53 gene mutations, loss of interferon alpha and beta (IFNA, IFNB) genes and lack of O6-methylguanine-DNA methyltransferase (MGMT) expression. Yet, in the studies performed to date, the relationship between these alterations has not been addressed. In this report, we have studied gene expression in 29 malignant glioma cell lines and have determined that, although loss of the interferon genes and loss of RB, p53 and MGMT mRNAs are frequent events, combinations of genetic alterations involving these four proven or putative tumor-suppressor genes are relatively infrequent. The exception was loss of RB mRNA, which may be associated with lack of MGMT mRNA. PMID- 1501895 TI - Characterization and cell cycle-regulated expression of mouse B-myb. AB - We have isolated a full-length mouse B-myb cDNA clone and used this to examine cell cycle-regulated expression of this gene. Mouse B-Myb was predicted to comprise 704 amino acids and to be 84% homologous with human B-Myb. There were three regions of extensive amino acid homology which may indicate functional domains: the first corresponded to the c-Myb DNA-binding domain, while the second had no counterpart in c-Myb but was instead homologous to a short segment of the related A-myb protein. The third region of homology is partially conserved in both c-Myb and A-Myb and may correspond to the c-Myb negative regulatory domain. Stimulation of quiescent 3T3 fibroblasts with serum was found to result in induction of B-myb expression in late G1 and to lead to high levels of gene transcripts that persisted through S phase. Similarly, maximum B-myb mRNA levels were reached in G2/M synchronized cells prior to entry into S phase. These results are consistent with a role in G1/S transition as has been suggested for c myb. PMID- 1501897 TI - [Clinical course of laryngeal cancer in relation to sex]. AB - In 1960-1987 2352 cases of larynx cancer were cured and observed. The number of the side men to women was in the ratio of 11.5:1. The cancer of epiglottis was prevailing in both sex but percentage of these cancers was higher in women's cases than men's (67.6% vs 62.7%). Besides women called for the treatment more often with the cancer in initial states of the disease (62.2% vs 53.4%). Five- year survivals (actuarial method) were higher amongst women (69.8% vs 60.0%). In the same state of clinical advancement of the disease, the 5-year survivals were also higher with women. In the cases of cancer in the early states of larynx cancer (I and II) the difference was about 5.0%, and among patients with cancer in the late state of the disease (III and IV) the difference was 8.4%. The last premise caused the authors to put forward the hypothesis that apart from the sooner calling for the treatment of women, there may also be other unknown phenomena, perhaps hormone--immune, conditioning higher index of survivals in women. PMID- 1501896 TI - [Evaluation of early results and failures of radiotherapy in patients with cancer of the oral cavity and throat]. AB - Since 1986 to 1989 in the Department of Teleradiotherapy of Center Oncology- Institute branch Gliwice 102 patients with oral cavity cancers and 114 with pharyngeal cancers were treated. Patients underwent external radiation, which was delivered with Co60 to the dose 70 Gy on the tumor and additionally regional lymph nodes were irradiated with 10 MeV linear accelerator. There were 69 patients (32%) with stage T-2 and 147 patients (68%) in stage T-3. Metastatic regional lymph nodes in 130 patients (60%) were recognized. Free of disease one year survival in 98 patients (45%) was observed: 41% with oral cavity cancer and 49% with pharyngeal cancer. The conclusion suggests that the results depend on the size of the tumor and presence of the metastatic lymph nodes. Among the patients with oral cavity cancer in 40% with free nodes and 69% with metastatic nodes unsuccessful treatment was observed. In the group with pharyngeal cancer percentage were 35% and 63% respectively. Results of the treatment, were unsatisfactory when diameter of metastatic nodes was more than 5 cm (N-3). PMID- 1501898 TI - [Supracricoid reconstructive laryngectomy with cricohyoidopexy and cricohyoidoepiglottopexy]. AB - On the base of the personal material, comprising 19 patients with glotto supraglottic cancer, an operative technique on supracricoid reconstructive laryngectomy with CHP and CHEP has been presented. The data achieved within 3 years allowed to evaluation of preliminary oncological and functional results. In the group of 19 operated patients, one case of local recurrence was found. Cervical recurrence was observed in 2 persons in the first year after the operative treatment. No remote metastases and secondary neoplastic++ focus were found in the digestive and respiratory tract. One patient died of massive pneumonia in the course of disturbances in deglutition. The most difficult problem of the postoperative period in the cases of CHP were the disturbances in deglutition. For that reason pneumonia was observed in 4 patients. Nasogastric tube was left in place for a mean time of 20 to 60 days. All CHEP patients were decannulated and 5 ones out of 14 persons group after the operation of CHP remain with tracheotomy tube. PMID- 1501899 TI - [Cancer of the pharynx--results of treatment with cobalt-60]. AB - One hundred two patients with pharyngeal cancer had been treated from 1980 to 1984 in Center Oncology--Institute branch Gliwice. Total radiation doses were 60 65 Gy. From the group of 44 patients without metastatic lymph nodes, 5 year survival rate was 36%. In cases with advanced pharyngeal carcinoma and with metastases to the lymph nodes (58 patients), 5 year survival rate was 18%. The results of this study suggest that survival rates depend on the size of the tumor and presence metastases to the local lymph nodes. PMID- 1501900 TI - [Serum ceruloplasmin activity in patients with cancer of the larynx]. AB - The ceruloplasmin activity of serum was measured in 50 patients with larynx cancer and 50 healthy subjects. The determination of serum ceruloplasmin based on the diamine oxidase activity with o-dianisidine as a substrate. In patients with laryngeal cancer the ceruloplasmin activity was significantly higher than that in healthy controls. The increase in the ceruloplasmin activity was correlated with clinical stage of larynx cancer. PMID- 1501901 TI - [Organization of the bone system of the nasal septum and its homologues. V]. AB - The aim of these anatomo-comparative investigations was the differentiation and systematization of the osseous nasal septum and vomer complex in rhesus monkeys (Catarrhina). ). The material consisted of 66 monkey heads: 52 of the fixed in formaline solution and 14 naturally macerated. The methodology was described elsewhere (part--1). The nasal osseous system philogenetically was presented in rhesuses only by alar bone. As lower--secondary part of septum emerges the typical parasphenoid complex. The alar bone in monkeys is homologous monominal elements (septal and subnasal bones) in pairhoofed mammals, birds, fishes and amphibians. It proves that in rhesuses as others Craniota the "mesoethmoid" and "ethmoidal bone" do not exist. In the skull of these monkeys the axially palate system was proved. This system does not dominate in the mechanics of the splanchnocranium. PMID- 1501902 TI - [The role of sclerotherapy in the treatment of esophageal varices in children]. AB - The authors presented the actual views and their own results of using sclerotherapy in children with oesophageal varices. Oesophageal varices exist almost every time as a most dangerous complication in patients with portal hypertension. Acute haemorrhage caries a high mortality and the extremely important priority is control of bleeding as soon as possible. Traditional conservative methods of treatment often do not improve long-term survival and portal systematic shunt is rarely possible in patients under the age of 10. Because of it sclerotherapy may be proposed as a treatment of choice for children with oesophageal varices. PMID- 1501903 TI - [Vestibular function in calcium and phosphate metabolism disorders in chronic renal failure]. AB - 45 patients with chronic renal failure (25 dialysed and 20 undialysed) were examined for function of vestibular organ and 35 patients with chronic renal failure treated by diet and drugs were examined for hearing acuity by pure tone audiometry and above-threshold audiometry. All patients serum sample's were examined for calcium, inorganic phosphates and uric acid. The examination revealed the damage of vestibular organ in 84.4 per cent of patients and statistically significant increase of parathormone serum concentration in patients with central type of damage. The hearing loss was found in 51 per cent of patients. The hearing loss in most number of cases was symmetrical and it was mainly the extracochlear auditory damage. The role of disturbances in calcium and phosphates metabolism in the pathogenesis of hearing loss seems to be unsure. PMID- 1501904 TI - [Instruments for microsurgery of the ear]. PMID- 1501905 TI - [A case of metastasis of clear cell carcinoma of the kidney to the hypopharynx]. AB - A rare case of kidneys clear cell carcinoma metastasis to the laryngopharynx was described. The observed metastasis manifested itself only just three months after total left-sided nephrectomy and partial right-side nephrectomy because of clear cell carcinoma. PMID- 1501906 TI - [A case of surgery of the lingual thyroid gland]. PMID- 1501907 TI - [A case of esthesioneuroblastoma in a 25-year-old man]. PMID- 1501908 TI - [35th anniversary of surgical activities at the Otolaryngology Department of the District Merged Hospital in Zielona Gora 1953-1987]. AB - 40,506 patients were treated at the Laryngology Department in the last 35 years. 30,787 surgical interventions were performed. The type and number of operations were analysed as well as their upward and downward tendencies. A considerable decrease in radical operations of the ears, antrotomies, antromastoidectomies and intracranial, ear and sinusal complications was noted; whereas the number of tracheotomies, laryngectomies and radical neck lymphadenectomies due to larynx neoplasm was increased. PMID- 1501909 TI - Clinical aspects of cochlear implants. PMID- 1501910 TI - Pennsylvania Medical Society membership directory 1992-1993. PMID- 1501911 TI - Surgical management of cerebral palsy. AB - Musculoskeletal manifestations of cerebral palsy (CP) change with growth, necessitating orthopaedic management. The goal of orthopaedic management, which may involve surgical and/or rehabilitative intervention, is to help each individual reach optimal functional ability and prevent deformity. Goals of surgical intervention are to improve function, decrease discomfort, and prevent structural changes that may become disabling. Knowledge of the basic surgical procedures to correct deformities as well as understanding the special needs of CP patients will help nurses successfully care for these individuals. PMID- 1501912 TI - Osteoporosis: the silent disease. AB - Osteoporosis is a major health problem in the United States. It affects 24 million Americans; women are affected 6-8 times more often than men. It is a disease that is associated with pain, disability, and death due to complications from fractures. Health interventions that prevent bone loss are more effective than trying to retard bone loss once an individual has osteoporosis. This article discusses prevention practices as they relate to nursing assessment and intervention. PMID- 1501913 TI - Transportation resources for pediatric orthopaedic clients. AB - Pediatric orthopaedic surgery clients may be unable to safely, comfortably, and affordably use child safety seats (car seats) for a variety of reasons. This article describes commercially available child safety seats suitable for transporting pediatric orthopaedic surgery clients. Discussed are those children with cerebral palsy, spina bifida, hip dislocations, arthrogryposis, scoliosis, and osteogenesis imperfecta. PMID- 1501914 TI - Variables associated with hypotension in postoperative total knee arthroplasty patients receiving epidural analgesia. AB - The purpose of the study was to identify variables that may place the total knee arthroplasty patient receiving epidural analgesia at risk for hypotension postoperatively. A review of medical records of this convenience sample of 99 subjects was conducted in this retrospective, descriptive, correlational study. Variables predictive of postoperative hypotension using stepwise multiple regression included low postoperative systolic BP on the nursing unit the day of surgery (R2 = .26, p less than .001), low diastolic BP in postanesthesia room (R2 = .31, p less than or equal to .01), low hemoglobin the third postoperative day (R2 = .37, p less than or equal to .01), use of diuretics preoperatively (R2 = .40, p less than or equal to .05), and total fluid intake first day postoperatively (R2 = .43, p less than or equal to .05). These variables accounted for 43% of the variability in the occurrence of hypotension. Identification of variables predictive of hypotension should provide direction for future care givers and researchers. PMID- 1501915 TI - Using pulse oximetry to make clinical nursing decisions. AB - Pulse oximetry provides intermittent or continuous evaluation of a patient's oxygen saturation. Sound clinical nursing judgments can be based on oximetry readings if the nurse combines effective operation and trouble-shooting of the oximeter with knowledge of the principles of oxygenation and their relationship to a patient's total clinical picture. PMID- 1501916 TI - Heparin today, hirudin tomorrow? PMID- 1501917 TI - Orthopedic nursing practice guidelines. The NAON Standards Task Force. AB - The NAON Standards Task Force has revised Orthopaedic Nursing: Process and Outcome Criteria for Selected Nursing Diagnoses published jointly by the American Nurses' Association (ANA) and NAON in 1986. The new document is entitled Orthopaedic Nursing Practice Guidelines. It contains guidelines for the care of orthopaedic patients with 11 selected nursing diagnoses and is an important decision-making tool for orthopaedic nurses. This article contains excerpts from the new guidelines with suggestions for its use. PMID- 1501918 TI - Gerhard Domagk. PMID- 1501919 TI - Immunofluorescent test for AIDS introduced. PMID- 1501920 TI - Noncompressive spinal radiculitis. AB - Sciatica can be caused by a herniated disc (compressive neuropathy) or by the process of disc degeneration (noncompressive neuropathy). Laminectomy and discectomy usually produce a good result in compressive neuropathy, whereas surgery for noncompressive neuropathy, if necessary, consists of complete excision of the disc and anterior interbody fusion, posterior fusion, or both. Noncompressive spinal radiculitis is a biochemical, not a biomechanical, problem. Phospholipase A2, substance P, and increased fibrinolytic activity have been implicated in the process. PMID- 1501921 TI - Biomechanics of the human anterior cruciate ligament. ACL structure and role in knee motion. AB - Surgical reconstruction of the anterior cruciate ligament (ACL) to restore knee stability has introduced many subjects of debate, including graft selection, reconstructive technique, and postoperative rehabilitation. In the first part of this two-part review, the tensile properties of the human ACL and the role of the ACL in knee kinematics are discussed. Reconstructive techniques for ACL replacement with regard to the biomechanics of the ACL in normal and ACL deficient knees will be addressed in Part II. PMID- 1501922 TI - Postoperative course after total hip arthroplasty: wound drainage versus no drainage. AB - This retrospective study of 364 patients with total hip replacements performed between 1985 and 1990 showed no benefit in the use of drains and found an increased rate of transfusion associated with the use of drains. The two study groups (171 patients with two closed-wound suction drains in the wound and 193 patients closed without drains) differed in the type but not in the rate of wound problems; the drained group had more drainage at the port site, whereas the undrained group had more ecchymosis and swelling. There was no significant difference between the groups in operative blood loss; however, the drained group did require transfusions significantly more often than the undrained group (98 of 171 [57.3%] as opposed to 83 of 193 [43%], respectively). Of the patients requiring transfusions, patients with wound drains required significantly more blood than those without drains (1.12 versus 0.62 transfusions per patient for men; 1.73 versus 1.03 transfusions per patient for women). PMID- 1501923 TI - Congenital pseudarthrosis. AB - Five cases of congenital pseudarthrosis of the clavicle were treated with open reduction and fixation with appropriate-sized contoured plates and screws. Iliac bone grafts were used to bridge the gap in four patients; local bone graft was used in the fifth patient. Consolidation was noted an average of 3 months postoperatively in all five cases. The plate and screws were removed in all patients at an average of 16 months postoperatively. Average length of follow-up for the five patients is 4 years. Roentgenograms demonstrate that the clavicle has continued to grow normally. All five patients have pain-free full range of motion and are engaged in unrestricted activities. PMID- 1501924 TI - Chondromyxoid fibroma. AB - Chondromyxoid fibroma (CMF) is the least common cartilage-producing tumor. In Dahlin and Unni's series of 8,542 bone tumors, 39 of which were CMF, none were found in the femoral shaft. In this case, a CMF in the femoral shaft presented initially as a pathologic fracture. Attempts at curettage and autogenous bone graft failed, and en bloc resection and segmented allograft reconstruction were eventually required. PMID- 1501925 TI - Imaging rounds. Bizarre parosteal osteochondroma. AB - The following case is presented to illustrate the roentgenographic findings of a condition of interest to the radiologist and orthopaedic surgeon. Initial history, physical findings, and roentgenographic examinations are presented along with the final histologic and roentgenographic differential diagnosis. PMID- 1501926 TI - A new goniometer. AB - A newly designed goniometer is presented for rapid and accurate measurement in the orthopaedic practice. This new instrument consists of two extensible arms with special calibrations. With proper adjustment of these arms, common and specific angles, such as the Cobb angle, can be measured easily and accurately. Specific calculations of various indices can be done quickly with special calibrations on the arms. This new instrument is simple, convenient, and accurate. PMID- 1501927 TI - Use of the tibial curved driving piece for AO femoral nail insertion. AB - The purpose of this article is to demonstrate an improved method of AO femoral nail insertion. The AO/ASIF Universal Femoral Nail (Synthes, Paoli, Pennsylvania) has proven effective in the treatment of femoral shaft fractures. The procedure is sometimes difficult when nailing in the supine position, especially with large or obese patients. The ram device impinges on the flank soft tissue of the patient. By using the curved driving piece (355.16) attached to the femoral set, the ram and the ram rod are brought away from the patient's side, thus allowing a less obstructed nail insertion. PMID- 1501928 TI - Improving the C-arm image of small bones. AB - The C-arm image of a small bone can sometimes be improved by suspending the extremity in the air, rather than positioning it flat on the operating-room table in the traditional manner. The C-arm roentgenogram is a modern development that allows rapid visualization of a roentgenographic image via computer enhancement of a low, k-voltage shot. As with any technical advance, it has its limitations; for small bones and bones involving growth plates, it is frequently deceiving. PMID- 1501929 TI - Sprains and strains. PMID- 1501930 TI - Inclusion of fellowships within the training program of orthopaedic surgeons. PMID- 1501931 TI - Inclusion of fellowships within the training program of orthopaedic surgeons. PMID- 1501932 TI - Inclusion of fellowships within the training program of orthopaedic surgeons. PMID- 1501933 TI - Inclusion of fellowships within the training program of orthopaedic surgeons. PMID- 1501934 TI - Sonographic imaging of the thyroid gland in congenital hypothyroidism. AB - We have attempted to facilitate differential diagnosis of etiological types of congenital hypothyroidism using real-time ultrasonography. Sonography of the thyroid gland was performed on 418 normal children, and 23 patients with congenital hypothyroidism and hyperthyrotropinemia. The thyroid gland was imaged by transverse scanning at the neck; the maximum thickness and the maximum width of the right and left lobe were measured. On the basis of the normal thyroid gland size obtained from normal children, the thyroid gland image of the patients were classified into 4 types: large image, normal image, small image, and no image of the thyroid gland at the neck: no image of the thyroid gland indicated agenesis or ectopia; large thyroid gland image indicated goitorous hypothyroidism. On the other hand, normal or small thyroid gland image probably included mild or transient forms of hypothyroidism, and transient hyperthyrotropinemia; these 2 types required further examination to complete the diagnosis. We concluded that real-time ultrasonography of the thyroid gland was a useful diagnostic imaging technic for patients who revealed elevated serum thyrotropin on neonatal mass-screening. PMID- 1501935 TI - The bubble sign in the gasless abdomen of the newborn. AB - The bubble sign (BS) in the gasless abdomen of the newborn is a helpful clue in the diagnosis of an upper gastrointestinal obstruction. The already swallowed air serves as the natural contrast agent. The single, double and triple BS are described in view of 23 cases indicating the level of the obstruction, and its differential diagnosis is discussed. The presence of BS in the gasless abdomen of the newborn is an indication for surgery until proved otherwise. With the increasing experience by ultrasonography, this modality should be considered as the first bed-side procedure when suspecting upper gastrointestinal obstruction, and then be confirmed by radiograms. PMID- 1501936 TI - The plain abdominal film in intussusception: the accuracy and incidence of radiographic signs. AB - The incidence of four plain abdominal film features associated with intussusception was recorded by four observers in 180 films of patients with intussusception mixed with 100 films of control subjects. The crescent sign and target sign were the most accurate indicators of intussusception. The target sign was the commoner being seen in 68% of films. Signs of small bowel obstruction were not useful in the diagnosis of intussusception. The soft tissue mass was the commonest indicator of intussusception. The soft tissue mass was found more commonly, however, than small bowel obstruction in the control subjects who did not have intussusception. PMID- 1501937 TI - Value of sonography including color Doppler in the diagnosis and management of long standing intussusception. AB - 15 cases of intussusception with presenting symptoms of more than 24 h duration were studied by sonography and Doppler. The aim of the study was to determine the validity of the sonographic criteria of peritonitis and bowel ischaemia in order to reduce the risk of colonic perforation and to increase confidence in achieving a successful hydrostatic reduction. The results were reviewed retrospectively and cases divided into 2 groups. Cases in group 1 were reducible by barium enema while those in group 2 required surgical intervention. Sonographic features of peritonitis were absent in all cases of group 1 and 3 cases of group 2. These 3 cases were reduced manually at surgery while the other 5 cases in group 2 with positive features of peritonitis required bowel resection. Blood flow was documented by colour flow Doppler in all cases except the 3 cases with gangrenous bowel in group 2. When sonographic features of peritonitis and loss of blood flow to the intussusception are present in late intussusception, surgical intervention is required. On the other hand, enema reduction should be pursued when such features are absent. PMID- 1501938 TI - Contrast enema diagnosis of necrotizing enterocolitis. AB - Contrast enema was performed in a select group of 126 neonates with ambiguous diagnosis of necrotizing enterocolitis (NEC). Enema findings were compared with that on plain abdominal radiographs (AXR) and the clinical outcome. Thirty-one of the 34 patients with a discharge diagnosis of NEC were interpreted to have a positive contrast enema, and 91 of the 92 patients without a discharge diagnosis of NEC were interpreted to have a negative contrast enema. The AXR was interpreted as positive in 57 patients and as negative or indeterminate in 69. Not a single case of perforation was produced. Judicious use of contrast enema can improve specificity of diagnosis in cases with discordant clinical and plain radiographic findings. PMID- 1501939 TI - Recurrent pneumatosis intestinalis in young infants. AB - In 67 infants with necrotizing enterocolitis (NEC) at Children's Hospital of Michigan from 1987-1990, three had recurrent pneumatosis intestinalis (PI) after the neonatal period and after hospital discharge. All three infants were premature (26-34 weeks), and one had an additional risk factor of gastroschisis. All three had their initial episode of NEC within the first month of life. Two had bowel resections, and one was treated medically. 15 h to seven months after discharge from the hospital, all three infants developed recurrent PI at ages ranging from 2.5 to 9 months. Two of the infants had free intraperitoneal air. Though all three infants had PI, only one had true recurrent NEC with ischemic bowel and died. This baby was the only one with rotazyme positive stools. The second infant, who had surgery for gastroschisis, had incomplete obstruction secondary to adhesions resulting in PI. Since surgery this infant has thrived. The third infant had extensive PI of the colon with free air. At surgery there was no evidence of bowel perforation. The free air was attributed to rupture of one of the many colonic cysts of PI. Subsequently, the child has done well. Recurrent PI in infants who have had NEC is unusual and the causes are varied. Because more neonates are surviving NEC, the pediatric radiologist needs to be aware of this delayed complication. PMID- 1501940 TI - Deep cerebral venous thrombosis in thalamo-ventricular hemorrhage of the term newborn. AB - Unilateral thalamic bleeding with associated intraventricular hemorrhage is reported in three full-term neonates. The first presented within 48 hours from birth with early onset streptococcal meningitis, persistent pulmonary hypertension, tonic seizures and a tense fontanelle. The second presented 6 days after birth with irritability, opisthotonus, a tense fontanelle and tonic seizures. The third was admitted three days after birth with seizures and a tense fontanelle. In the latter two infants NMR and CT imaging documented thrombosed superficial and deep cerebral veins. The etiopathogenesis of intracranial venous thrombosis in the neonate is diverse: asphyxia, dehydration, polycythemia, sepsis meningitis and difficult delivery are the main causes. In one of our patients jugular vein compression by the collar of a negative-pressure ventilation chamber probably initiated the intracranial events. More than half of the survivors sustain severe neurological impairment. PMID- 1501941 TI - Reverse flow in the intracranial arteries--the possible significance of comparative flow in the anterior cerebral and the basilar arteries. AB - Four infants with reverse flow patterns of the intracranial arteries are reported. Two with severe brain damage, had a reverse flow pattern in the anterior cerebral artery, which was recorded during the recovery stage from cardiac arrest. The other two patients showed a reverse flow pattern in the basilar artery and had a good prognosis. Reverse flow in the anterior cerebral artery suggests severe brain damage, but that in the basilar artery does not. PMID- 1501942 TI - Dysplastic gangliocytoma of cerebellum in a newborn. Diagnosis by ultrasonography and MRI. AB - A cerebellar lesion was detected by ultrasonography (US) in a symptomatic newborn. Magnetic Resonance Imaging (MRI) demonstrated this lesion as a gyriform structure. Therefore a rare dysplastic gangliocytoma was suspected, which was compatible with histopathology. Immunohistochemical studies (monoclonal antibody Ki-67) showed signs of progression. PMID- 1501943 TI - Congenital primary cerebral angiosarcoma: CT, US, and MR findings. AB - Congenital primary intracranial angiosarcoma (CAS) is an exceptionally rare tumor. To our knowledge the imaging features of intracranial angiosarcomas have only been briefly mentioned in the neuropathologic literature. To our knowledge, only one case of CAS has been reported. We present a case of a pathologically proven CAS found in a neonate. PMID- 1501944 TI - Bilateral choroid plexus carcinoma of the lateral ventricles. US, CT and MR findings. AB - This is a case report of a bilateral choroid plexus carcinoma (CPCa) of the lateral ventricles in whom contralateral ventricular dissemination was thought to be due to seeding. The disease was diagnosed by ultrasonography; CT and MRI confirmed the pre-operative diagnosis. PMID- 1501945 TI - Choroid plexus angioma: a rare cause of cerebral hemorrhage in childhood. PMID- 1501946 TI - Early childhood presentation of neurovascular disease in hereditary haemorrhagic telangiectasia. AB - This paper describes an unusual case of hereditary haemorrhagic telangiectasia related cerebrovascular disease with an arteriovenous malformation and aneurysm presenting with intracranial haemorrhage in early childhood. PMID- 1501947 TI - "Brown tumor" of the maxilla. AB - A case of brown tumor of hyperparathyroidism in a young girl with a long history of chronic renal failure and hemodialysis therapy is reported. The diagnosis can be reached with the aid of the classic skeletal radiological sign which address the evaluation of both CT and MR imaging. PMID- 1501949 TI - CT diagnosis of gastric rupture following blunt abdominal trauma in a child. PMID- 1501948 TI - Involvement of the white matter in the initial stage of herpes simplex encephalitis. PMID- 1501950 TI - Pedunculated colonic polyp diagnosed by colonic sonography. AB - A solitary hamartomatous polyp of the colon in a four year old boy was diagnosed by colonic sonography while barium enema and colonoscopy were non-diagnostic. Colonic sonography provides an additional simple, relatively non-invasive modality for evaluation of the colon. PMID- 1501951 TI - Benign mediastinal lipoblastoma in a 14-months-old infant. AB - Lipoblastomas are rare benign tumors arised from the fetal-embryonal fat that occur almost exclusively in children. About 70% of them arise in the limbs but several other sites have been reported. To date there are only 4 cases of mediastinal lipoblastoma in children, described in the international literature. The radiologic examination, including the chest X-ray, sonography and CT scan, can be used to detect the mass and its relationship to surrounding structures, and to define the typical features of the fat-like tissue. A case of a mediastinal lipoblastoma in a 14-months-old infant is reported, with a respiratory stridor and occasional dyspnoea, appearing only in the supine position. The radiologic findings, treatment and follow-up are also described. PMID- 1501952 TI - Branchial fistula: CT manifestations. AB - A patient with a recurrent left neck abscess was found to have a branchial fistula from the pyriform sinus. This uncommon anomaly was demonstrated by CT and barium swallow. The embryology, pathology and clinical features of this lesion are discussed and contrasted with those of the branchial cyst. PMID- 1501953 TI - Bronchoesophageal fistula of tuberculous origin in a child. AB - Bronchoesophageal fistulas (BEF) are uncommon in children, the etiology being congenital or acquired. Acquired bronchial perforation of tuberculous origin is common in children with pulmonary tuberculosis but bronchoesophageal perforation secondary to tuberculosis and leading to a fistulous tract formation is rare. To date, there have only been 4 case reports of BEF of tuberculous origin in children. We present yet another case of an acquired BEF of tuberculous origin in a child who presented with a sudden onset of dysphagia and choking sensation. PMID- 1501954 TI - Lymphangioma of the lung associated with respiratory distress in a neonate. AB - Congenital pulmonary lymphangioma involving the entire left lower lobe in a newborn is reported. Respiratory distress was the presenting symptom. Radiography was suggestive of congenital diaphragmatic hernia or congenital cysts of the lung. PMID- 1501955 TI - Echocardiographic assessment of radiation-induced mitral valve disease in a child. AB - A young girl, previously treated with mediastinum irradiation because of a pulmonary fibrosarcoma, developed mitral valve disease with valvular insufficiency. In consideration of the clinical course and the echocardiographic findings, authors hypothesize a relation between the radiation therapy and the valvular damage. PMID- 1501956 TI - An autosomal recessive variant of spondylo-epiphyseal dysplasia in three sibs. AB - A report of one male and two female sibs with an unusual form of spondylo epiphyseal dysplasia (SED) manifesting in late childhood. The anomalies are pronounced at the femoral head. There is platyspondyly with biconcave deformation and irregular vertebral end-plates. As the parents are healthy autosomal recessive inheritance is likely. PMID- 1501957 TI - Spondylometaphyseal dysplasia, type VII. AB - Spondylometaphyseal dysplasia was first described by Kozlowski et al. in 1967 as a new dysplastic bone disease, characterized by metaphyseal dysplasia associated with generalized platyspondyly in the vertebral column [1]. Kozlowski et al. have pointed out the autosomal dominant transmission of this disorder at that time. However, later reports showed that the manner of genetic transmission and the degree of the manifestation of the radiological findings could be variable and accordingly seven types of spondylometaphyseal dysplasia were described [2]. In this article, three cases displaying one of the rare forms of spondylometaphyseal dysplasia, "type VII" are presented and the diagnostic findings as well as the differential diagnostic criteria are discussed. PMID- 1501958 TI - Platyspondylic lethal osteochondrodysplasia: Shiraz type with radiological pathological correlation. AB - We report two cases of a platyspondylic lethal osteochondrodysplasia in siblings. The condition affects predominantly the metaphyses of the axial skeleton associated with limb shortening and mild platyspondyly. The radiological and pathological features correlate very closely with Sedaghatian's lethal metaphyseal chondrodysplasia, which has previously been described only in Iranian Nationals. Both the radiological and pathological appearances will be described, together with a discussion of the differential diagnosis, the genetical implications and a review of literature. PMID- 1501960 TI - Sonographic findings of testicular teratoma with pathologic correlation. AB - Testicular teratoma is a rare tumor in children. We recently encountered two boys, aged 18 months and 2 years respectively, with this tumor. Sonography revealed an intratesticular mass in both. The first revealed a predominantly cystic lesion with echogenic components along its wall. The second showed a complex mass occupying most of the right testicle, and containing several areas of calcifications and cysts. Excellent pathologic correlation was obtained in both. Preoperative diagnosis of testicular teratoma is possible if the characteristic features are recognized. The prognosis is good following orchiectomy in the pediatric patients. PMID- 1501959 TI - Phase III clinical evaluation of gadoteridol injection: experience in pediatric neuro-oncologic MR imaging. AB - Twenty-two pediatric patients with known CNS neoplasms underwent magnetic resonance (MR) imaging before and after intravenous injection of 0.1 mmol/kg gadoteridol injection as part of a Phase IIIB open label multicenter clinical trial. Intravenous administration of this neutral, nonionic contrast agent was found to be safe in children. No clinically relevant changes in vital signs or laboratory values (including complete blood count, blood chemistry, serum electrolytes, thyroid and metabolic panel and clotting function) were attributed to the administration of gadoteridol injection. There were no systemic complaints. The imaging characteristics of gadoteridol in pediatric CNS disease appeared similar to those of gadopentetate dimeglumine. Contrast enhancement was present in 17 of 22 patients (77%). The administration of gadoteridol injection provided additional clinically relevant information including improved visualization and delineation of the primary lesion, detection of additional lesions, determination of tumor recurrence and narrowing the list of differential considerations in all 17 enhancing studies as well as in 2 of 5 studies without signal intensity enhancement. The very low toxicity, inherent to this nonionic low osmolal paramagnetic contrast formulation may allow administration of increased doses at increased infusion rates for an increased number of indications with improved sensitivity. PMID- 1501961 TI - Contributions to the history of psychology: LXXXV. Jean Piaget, student of Pierre Janet (Paris 1919-1921). AB - This article provides information about an important period of Piaget's formative years, those he spent in Paris from 1919 to 1921, during which he came into contact with eminent members of the French scientific and philosophical community of the time. Among these was the psychiatrist and psychologist Pierre Janet, whose genetic approach to the psychology of behaviour and ideas about the hierarchical organization of psychological functions converged with Piaget's early scientific interests and provided Piaget a conceptual framework within which to work and develop his own project of studying the genesis of knowledge. PMID- 1501962 TI - Locus of control and perceptions of human aggression. AB - 116 college students were given a locus of control scale and a measure of misconceptions about human aggression. A negative correlation of -.52 indicated that as feelings of mastery and control increased, belief in a human propensity for aggression decreased. PMID- 1501963 TI - Conservation of distance in African children from rural and urban schools. AB - This paper contains a review of the small literature on the association of rural/urban residence and attainment of distance conservation among African children and an account of a study of the age at which children in Sierra Leone, West Africa, attain conservation. 150 children from the ages of 8 to 18 years, from rural and urban schools, were assigned Piagetian tasks to judge their conservation of distance. Analysis showed that at 11 + years, conservation was observed and that there was no significant difference between the urban sample and the rural one. Several confounds in the data limit conclusions but use of the children's own languages was possible in some experiments. PMID- 1501964 TI - Toe graphaesthesia as a discriminator of brain impairment: the outstanding feet for neuropsychology. AB - Because of the vulnerability of the medial surfaces of the cerebral hemispheres to the consequences of shear forces, we hypothesized that quantitative sensori motor deficits for the feet would be strong indicators of general brain dysfunction. On the basis of the Halstead-Reitan Impairment Index, 28 adults who had received closed head injuries were assigned to perfectly normal, normal, or (mildly to severely) impaired groups. Foot tap and finger tap as well as agnosia and graphaesthesia for the fingers and toes were measured. Deficits in toe graphaesthesia were the most powerful group discriminator. Potential usefulness of haptic/motor, finger/toe comparisons for recording the progress of degenerative diseases, such as AIDS, is also suggested. PMID- 1501965 TI - Symmetry in building block design for learning disabled and nonlearning disabled boys. AB - This study examined perceptual differences in symmetry with and without a model between 21 learning disabled boys with reading deficits and 28 learning disabled boys with deficits in mathematics. 55 nonlearning disabled boys served as controls. All boys were in Grades 3, 4, or 5. Without a model, all learning disabled boys built significantly more asymmetrical building block designs than nonlearning disabled boys. However, with a model, all learning disabled boys could imitate the model, but it took them longer to complete the task successfully. All boys appeared to have difficulty in modeling asymmetrical tasks, taking more time for task completion after seeing an asymmetrical model. This study suggests modeling perceptual tasks might be an effective teaching strategy for such children. PMID- 1501966 TI - Improving African children's cognitive development through training. AB - According to Piaget, cognitive development can be realized with maturation and environmental experience, but he attached some significance to training as a means of facilitating cognitive development. This paper gives brief summaries of eight studies carried out in Africa clearly showing that cognitive development can be facilitated by training. PMID- 1501967 TI - Hemisphere differences in event-related potentials (ERPS) to monaural presentations of simple speech sounds. AB - The aim of the present study was to compare ERPs over the left and right hemispheres to monaural consonant-vowel (CV) syllables. It was predicted that, if the contralateral auditory representation is stronger than the ipsilateral one, then ERPs over the left hemisphere should be larger for right-ear stimulus input. Furthermore, if the hemispheres differ in efficiency in processing of speech sounds, then ERPs recorded at any given site should vary as a function of the ear to which the sound is presented. Twelve right-handed subjects participated. The CV-syllables used were /Ba/ and /Pa/ with 15 presentations of each syllable to each ear in a randomized order. EEG was recorded from F3, Fz, and F4 with linked ears as reference. The results showed no significant asymmetry in the ERP-leads. N1- and N2-amplitudes were, however, larger at Fz than at F3 and F4, and N1 latency was shorter for right-ear presentations, which also interacted with the /Pa/-syllable presentations. P3-latency was longer to the /Pa/-syllable compared to the /Ba/-syllable, while N4-latency was longer to the /Ba/-syllable. N4 amplitude was more negative for the /Pa/-syllable presented to the left ear. The results are discussed in terms of phonemic differences between the unvoiced /Pa/ and voiced /Ba/, and early versus late stages of processing. The results are also seen in relation to ear differences in dichotic listening. PMID- 1501968 TI - Listeners' perceived verbal and nonverbal behaviors associated with communicators' perceived understanding and misunderstanding. PMID- 1501969 TI - Confirmation of Tabachnick and Klugman's hypothesis that the death instinct is constant. AB - In reporting the accident death rate and the chronic liver disease death rate for 1980, the Bureau of the Census divided the United States into nine areas. To test Tabachnick and Klugman's hypothesis that the amount of death instinct per capita remains constant across regions, the 1980 death rates for accidents and chronic liver disease were correlated. Contrary to earlier studies, the present study gave support for Tabachnick and Klugman's hypothesis. PMID- 1501970 TI - Perspectives of research participants, psychologist investigators, and institutional review boards. AB - This study investigated the views of 100 student research participants, 107 psychologist investigators, and 45 members of Institutional Review Boards (Human Subject Committees). Participants in these three groups responded to questions regarding the ethical parameters of a fictitious psychological research protocol. Psychologist investigators' endorsements are similar to those of Institutional Review Board members when the debriefing procedure of the protocol and its potential benefits to others are questioned. The views of psychologist investigators are similar to those of students when the topic of risks to participant is at issue. Implications of these findings for review of research proposals in psychology by Institutional Review Boards are discussed. PMID- 1501971 TI - Willingness to take legal action in wrongful dismissal cases: perceptual differences between men and women. AB - 146 business students with full-time work experience participated in a study of dismissal from employment. Based on self-ratings, men were more likely than women to favor court action in the event of dismissal. PMID- 1501972 TI - Relation of anxiety about social physique to location of participation in physical activity. AB - The purpose of this study was to examine the relationship of anxiety about social physique to location of participation in physical activity. 37 nursing students completed the Social Physique Anxiety Scale and answered questions relating to the location of the physical activity in which they participated. Women were assigned to either a high- or low-anxiety group based on these scores. An examination of the reported location where participation in physical activity occurred showed that more high than low scorers reported a tendency to exercise privately than publicly; the number was higher than expected. Perhaps high scorers prefer exercise settings that provide less opportunity for their physiques to be evaluated. PMID- 1501973 TI - Biochemical and galvanic skin responses to music stimuli by college students in biology and music. AB - The purpose of this study was to examine biochemical and physiological responses to musical stimuli. Specifically, university music and biology students' plasma levels of norepinephrine, endorphin, and cortisol, and their galvanic skin responses were measured before and after listening to two different musical selections in an anechoic chamber and during controlled silence. The results indicated that biochemical variables changed significantly in both groups during listening to music but were not different during the controlled silence. These data suggest that music majors may listen more analytically to music. GSR responses were significantly higher for music majors than biology majors, and plasma cortisol increased in music students but decreased in biology students. Music which elicits specific emotions induces physiological changes which may be beneficial to relaxation and behavioral therapies. PMID- 1501974 TI - Fundamental frequency variability in elderly women during production of stressed and unstressed words. AB - The purpose of this investigation was to examine intrasubject and intersubject fundamental frequency (F0) variability in a group of young adult and elderly female speakers during the production of stressed and unstressed words. While both groups exhibited greater intersubject variability during stressed versus unstressed productions, stressed productions were more variable in the elderly women than in the young adults. Also, the elderly women exhibited greater intrasubject variability during stressed and unstressed productions relative to young adults. Implications of these findings were discussed. PMID- 1501975 TI - Effects of listeners' experience on two measures of intelligibility. AB - 10 speech-language pathologists with extensive experience in judging speakers' intelligibility and 10 control subjects with no such previous experience provided written identification and magnitude-estimation scaling judgments of the intelligibility of nine audiotaped speech samples. Analysis indicated no significant main effect for experience on either the written identification or the magnitude-estimation scaling tasks. Implications for the continued use of magnitude-estimation scaling as a measure of speech intelligibility are discussed. PMID- 1501976 TI - Art training and the Rey figure. AB - A 55-yr.-old woman who had had a meningioma removed many years previously performed well on various neuropsychological tests but showed apparent gross loss of gestalt in copying the Rey figure, and poor subsequent recall of the figure. Further investigation suggested that her copying style was at least partly attributable to her training in art and that she was capable of copying in a more usual fashion with subsequent improvement in recall. PMID- 1501977 TI - Consistency of interform content for the Gordon Test of Visual Imagery Control. AB - A total of 116 undergraduates (49 men, 67 women) completed the Gordon Test of Visual Imagery Control followed immediately by another form. Scores were higher for women than for men and on the original than on the new version. Alternate form reliability coefficients were .517 for the complete sample, .712 for men, and .210 for women. It was concluded that consistency across content was lower than desirable. PMID- 1501978 TI - Comment on Nelson, et al.: 'Comparative time estimation skills of Hispanic children'. AB - Recently Nelson, Smith, Dodd, and Smith reported a dissipation of a cross cultural difference in time estimation. A number of difficulties in this study are noted and a recommendation for further research is provided. The difficulties include an inappropriate jump to a conclusion about future perspective and the restriction of the dissipation of the cross-cultural difference to Grade 5 children. Research on children beyond Grade 5 would demonstrate the durability of the dissipation reported. PMID- 1501979 TI - Comparison of Kaufman's short form of the McCarthy Scales of Children's Abilities and the Stanford-Binet Intelligence Scales--Fourth Edition. AB - 21 kindergarten children completed the Stanford-Binet-IV (Binet-IV) and the McCarthy Scales of Children's Abilities. Kaufman's (1977) estimated General Cognitive Index (GCI) was computed from the entire McCarthy scales. There was only one significant difference among the Binet-IV and estimated GCI scores. Abstract/Visual Reasoning was significantly lower than the Kaufman GCI. Correlations of the five Binet-IV Standard Age Scores and the Kaufman GCI ranged from .29 to .67. The correlation between the GCI and the Kaufman estimated GCI was .91. PMID- 1501980 TI - Psychological aspects of chronic fatigue syndrome. PMID- 1501981 TI - Addressing the psychosocial needs of orthopedic pain patients. AB - Analysis of comprehensive examinations of 258 patients with orthopedic pain yielded 5 types of pain responders. Research is under way to analyze the response to pain and effectiveness of response treatment for each type of pain responder. PMID- 1501982 TI - Differential diagnosis of disturbed adolescents with the Minnesota Percepto Diagnostic Test-Revised. AB - Two groups of psychiatric adolescent patients (19 schizophrenics, 22 nonschizophrenics) on an acute inpatient ward of a general hospital were compared for their performance on the Minnesota Percepto-Diagnostic Test--Revised. The effects of admission on test performance were also investigated. Results supported the efficacy of the test in differentiating between the two groups. The schizophrenic adolescents scored significantly less well (higher rotation scores) than the nonschizophrenics. It was shown that the groups' test performance significantly improved from admission to nine days later. PMID- 1501983 TI - Hemisphericity style, sex, and performance on a mirror-tracing task. AB - 60 right-handed college students classified as preferring either a style of left or right hemisphericity mirror-traced a star pattern once with each hand. Speed of tracing and number of deviations outside the star pattern were the dependent measures. Analysis showed no statistically significant differences in performance between right- and left-style groups or between men and women. However, subjects classified as showing a right-hemisphericity style mirror-traced the star pattern significantly faster and more accurately with the left hand than with the right. The left-hemisphericity-scoring group displayed a nonsignificant tendency to perform better on the reverse pattern. PMID- 1501984 TI - Perception of loudness and musical preference: comparison of musicians and nonmusicians. AB - To estimate the relationship between musical preference and perceived loudness, 25 subjects, musicians and nonmusicians, were asked to match the loudness of a neutral stimulus to a given musical selection. Ten different types of music were used; each was rated for likability by the subject. Over-all analysis of loudness ratings indicated that nonmusicians were more accurate in matching loudness of a neutral stimulus with the musical selections. This finding suggests differences in loudness perception between musicians and nonmusicians. Both groups were most accurate on the selection which could be inferred as most familiar. PMID- 1501985 TI - Effects of four physical education teaching methods on development of motor skill, self-concept, and social attitudes of fifth-grade children. AB - The purpose of this study was to examine the effects of four teaching methods on several measures of motor skill, self-concept, and social attitudes of 130 fifth grade children (67 boys, 63 girls), who were randomly chosen from five elementary schools in one area. Teaching methods were systematically applied for 60 teaching days (20 weeks). Measurements were assessed on three occasions (pre-, mid-, and post-experiment). A 4 x 2 x 3 multivariate analysis of covariance showed the 'combined' method most effective in improving the students' motor ability, while 'indirect' and 'game-oriented' methods contributed to the improvement of self concept and social attitudes, respectively. Since each of the four methods had different effects on various measures made to evaluate whether aims of physical education had been met, the teacher should be aware of many methods and able to implement them in various combinations, depending upon the special features and purposes of a lesson. PMID- 1501986 TI - Binocularity and photophobia in intermittent exotropia. AB - The relationship between photophobia and binocular function in intermittent exotropia was examined in 42 subjects (21 patients and 21 controls). In all subjects fusional amplitude and strength of binocular sensory status were tested before and during exposure to bright light. An explanation of photophobia in intermittent exotropia was suggested as impairment in binocular cooperation, since the indicators of binocular function were significantly altered in the patients, particularly during light exposure. PMID- 1501987 TI - Empirical evidence for assumptions underlying time orientation in undergraduates. AB - 282 undergraduate students between 17 and 68 years of age were asked to list the 5 most significant experiences of their lives, to assign the time zones to these experiences, and to provide estimates of emotional valence corresponding to each significant life experience they listed. Subjects also provided judgements of time perspective on a Life Line. The sample showed a near-past orientation and a positive emotional valence across the experiences reported. However, the first experiences reported were distant past experiences significantly more frequently than expected by chance, while the last experiences in the Experiential Inventory were significantly more often located in the distant future. While this result validates the prevailing assumption of a unidirectional flow of past to future, empirical evidence was also found for the larger magnitude and variability of future as compared with past perspective. This suggests a bidirectional model of time should be invoked to explain the differing character of the opponent temporal processes of recall and anticipation in human experience. PMID- 1501988 TI - Prison norms for Raven's Standard Progressive Matrices. AB - Prison norms for the Raven's Standard Progressive Matrices were developed using 1126 male inmates in a prison in Nevada. 556 of the men were white, 480 black, 55 Mexican, 19 Cuban, 9 Asian, and 7 Native-American. Norms were provided for three age categories--under 35 years, age 36 to 54, and all ages combined. Normative information was presented for white inmates, black inmates, and all ethnicities combined. There was substantial overlap in distribution of scores by black and white inmates. PMID- 1501989 TI - Knowledge and motor performance. AB - Traditionally, motor skill acquisition has implied that the performance of a given individual on a particular skill is dependent on the amount of prior practice of that skill. However, concepts such as schema theory, or kinetic formulae, or the strategic allocation of resources imply that, even when practising specific skills, performers gain knowledge about their own motor performance which can be used or applied to related or novel situations. An attempt was made to relate the performance of a complex psychomotor task to differing levels of motor skill expertise or knowledge (athlete and nonathlete). 20 subjects performed (1600 responses) on a novel pursuit or tracking task. Analysis indicated that the athletes performed significantly better. Their main advantage appeared to be more in their ability to control and produce fast, accurate movements than in their decision-making. Accepting Henry and Rogers' 1960 proposition that there is no such thing as a general motor ability or coordination factor does not imply that the only alternative is for all motor skills to be specific. It is argued that the differences in the present study arose from the athletes' greater knowledge (schema, kinetic formulae) related to their understanding of their own motor capabilities. PMID- 1501990 TI - Context effects in recall and recognition at various retention intervals. AB - This study investigated the differential effects of cuing in a number of contexts on recall and recognition at various retention intervals. Subjects were shown cue target word pairs and were asked to recall the target words under three sets of cues, varying in relation to the original cue. All 80 subjects completed a recognition task following the final recall task. Results suggest type of cuing does not have differential effects on recall and recognition; both recall and recognition are hindered by cuing in a number of different contexts, and the ability to recall improves over time, cuing, and exposure to the list. PMID- 1501991 TI - Use of subliminal stimulation to enhance learning mathematics. AB - 24 students, who participated in a summer session mathematics enrichment program, viewed subliminally presented messages. Prior to each class, the experimental group of 16 viewed a subliminally presented psychoanalytic merging message and the control group of 8 viewed a neutral message. After 20 sessions students were retested. Experimental students had higher mathematics scores than controls. These data are compared with results obtained by other investigators. PMID- 1501992 TI - Validation of an instrument to measure understanding of pattern by elementary school children. PMID- 1501993 TI - Comparison of parents' leadership styles: perceptions of parents and student leaders. AB - The Parent Leadership Style instrument was completed by 99 students enrolled in a leadership program and also by 129 of their parents. Data were analyzed and reported according to predominant leadership style (Telling, Selling, Participating, and/or Delegating) and effectiveness of leadership. A comparison was made between the parents' self-perceptions and how their children as student leaders perceived their parents. Some suggestions for parents are made relative to the development of leadership skills in students. PMID- 1501994 TI - Co-winner of the 1991 Dwight J. Ingle Memorial Writing Award. PMID- 1501995 TI - Professional profiteering? The ethics of physician entrepreneurship. PMID- 1501996 TI - RU 486: how abortion politics have impacted on a potentially useful drug of broad medical application. PMID- 1501997 TI - Coronary artery disease: diet-associated viruses as initiators. PMID- 1501998 TI - Survival of peas, peaches, and prenatal pigs. PMID- 1501999 TI - One hundred years of imaging: new benefits, new challenges. PMID- 1502000 TI - The Sinkovics hybridoma--the discovery of the first "natural hybridoma". PMID- 1502001 TI - The perils of "X-ray vision": How radiographic images have historically influenced perception. PMID- 1502002 TI - The influence of romantic literature on the medical understanding of pain and suffering--the stimulus to the discovery of anesthesia. PMID- 1502003 TI - Regression in renal cell carcinoma as re-expression of cell death in kidney development. PMID- 1502004 TI - Biology is beautiful. PMID- 1502005 TI - A search for the certitude of scientific facts with Giambattista Vico and Karl Popper: the importance of integrative physiology. PMID- 1502006 TI - Boundaries of psychiatry. PMID- 1502008 TI - Influence of co-medication on the metabolism of valproate. AB - Valproate is extensively metabolized in the liver and at least six main pathways which produce about 50 metabolites have been identified in man. The enzyme inducing antiepileptic drugs phenobarbital, primidone, phenytoin and carbamazepine increase total valproate clearance by 30-85%, whereas cimetidine and the new anticonvulsant compound striripentol display a small inhibitory effect (10-20%). Both carbamazepine and phenytoin induce a two-fold increase in the formation of delta 4-valproate and stimulate omega-oxidation and omega-1 oxidation. Acetylsalicylic acid causes a fall of 60-70% in the content in the urine of the metabolites of the beta-oxidative pathway, i.e. delta 2-valproate, 3 OH-valproate and 3-oxo-valproate, and an increase of glucuronidation (approximately 30%) and delta-dehydrogenation (approximately 20%). Stiripentol inhibits the formation clearance of delta 4-valproate by 30%. In the light of the possible therapeutic and toxic effects of some valproate metabolites, drug interactions with valproate at metabolic level may have important clinical implications. PMID- 1502007 TI - Differentiation between valproate-induced anticonvulsant effect, teratogenicity and hepatotoxicity. Aspects of species variation, pharmacokinetics, metabolism and implications of structural specificity for the development of alternative antiepileptic agents such as delta 2-valproate. AB - Valproate is metabolized into a large number of compounds via various metabolic routes. Metabolic profiles depend on species and age. Hepatotoxicity may be correlated with abnormal metabolism, especially in young age. Teratogenicity is associated with specific structural requirements: a free carboxyl atom connected to a carbon atom which also carries a hydrogen, and two carbon chains. This provides a clue for the development of alternative antiepileptic agents. PMID- 1502009 TI - Pharmacokinetics of valproate in pregnancy: mother-foetus-newborn. AB - An increased risk of seizures during and immediately after labour has been observed in epileptic women, and it is recognized that serum levels of antiepileptic drugs may decrease in pregnancy. Several studies have suggested that total valproate levels fall, but that free fractions increase during pregnancy. Recent findings suggest that the actual metabolism of valproate is not altered by pregnancy and that the changes of the plasma clearance are due primarily to decreased protein binding. The levels of free drug will not change significantly as pregnancy advances. However, dose reduction after delivery may be necessary to avoid toxicity. Valproate and its metabolites undergo placental transfer. In the foetus the plasma level of valproate and the protein binding are higher than in maternal plasma, and the half-life of valproate following placental transfer is considerably longer than in adults. Only small amounts of valproate appear in breast milk and those are not likely to cause any problems. During pregnancy and the first month after delivery preferably both total and free valproate serum levels should be closely monitored to determine the lowest effective dose. PMID- 1502010 TI - Valproate hepatotoxicity syndrome: hypotheses of pathogenesis. AB - Therapeutic use of the anticonvulsant valproate (VPA) has been associated with a rare, but severe and often fatal hepatotoxicity. Cases usually present with lethargy, anorexia, and vomiting with rapid progression to coma. Liver histopathology is characterized by steatosis with and without necrosis. In some instances only necrosis was present. Several hypotheses of pathogenesis have been postulated. These deal mainly with biochemical systems that are known to be affected by VPA, or with the possible idiosyncratic production of toxic VPA metabolites, especially delta 4-VPA. At present, no hypothesis entirely explains the diverse characteristics of the disorder. PMID- 1502011 TI - Metabolism of valproate to hepatotoxic intermediates. AB - A number of lines of evidence indicate that metabolites of valproate rather than the parent drug, mediate the microvesicular steatosis which characterizes valproate-associated liver injury. In this article, two mechanisms are discussed whereby valproate may cause hepatic steatosis through interference with the process of fatty acid beta-oxidation. In the first, valproate itself enters the mitochondrion where it completes for the enzymes and/or co-factors involved in the beta-oxidation of endogenous substrates, while in the second, valproate is metabolized via the hepatotoxic terminal olefin, delta 4-valproate, to a variety of chemically reactive intermediates which inhibit key enzymes in the beta oxidation cycle. PMID- 1502012 TI - Neural tube defects in association with epilepsy and its treatment. PMID- 1502013 TI - Effects of valproate on xenobiotic biotransformation in rat liver. In vivo and in vitro experiments. AB - Male Wistar rats were in vivo exposed for 2 weeks to 100 micrograms/ml sodium valproate by subcutaneous implantation of osmotic pumps and hepatocytes were isolated. As an in vitro model co-cultures of rat hepatocytes with epithelial cells were daily treated with valproate (25, 50, 100, 200 micrograms/ml) for 2 weeks. In both models the cytochrome P-450 content and the enzymatic activities of 7-ethoxycoumarin O-deethylase, aldrin epoxidase and glutathione S-transferase were determined in valproate-treated hepatocytes, in controls and in phenobarbital-induced cells. It appeared that in both systems the cytochrome P 450 content and the 7-ethoxycoumarin O-deethylase activity increased significantly after valproate treatment. On the other hand, the activities of aldrin epoxidase and glutathione S-transferase decreased. A cDNA probe, encoding rat P450IIB2 was used to determine whether mRNAs encoding the P450IIB subfamily were induced by valproate. It became clear that the inducing effect of valproate was even more pronounced in vitro than in vivo. PMID- 1502014 TI - Strategies for identifying and developing new anticonvulsant drugs. AB - The identification of new anticonvulsant drugs depends on the use of different animal models of epilepsy. The models should be mechanism-independent, able to screen a large number of compounds, at limited cost and technical expertise. Primary screening models include genetic or reflex models of epilepsy and electrically and chemically induced seizures. Once active compounds have been identified, more advanced mechanistic and seizure-specific models are needed to refine the choice of a lead compound. These can be either in vivo or in vitro models. Models known to interact with specific receptors or the production of the putative neurotransmitters of neural excitability or inhibition are valuable in assessing possible mechanisms of action. In vitro models have evolved as important tools in correlating changes in electrical phenomena and therapeutic spectrum. The use of the hippocampal slice and the cultured neuron permits classification of anticonvulsant activity based on cellular actions of the drug. Interactions by the experimental drugs with specific subcellular fractions of the central nervous system augment information on possible mechanisms of action. The final choice of compounds for development requires synthesizing and comparing all of the pharmacodynamic information with the pharmacokinetic and toxicologic data. In the final analysis, no single animal model of epilepsy known today can assure the development of better drugs for all treatment of the epilepsies. PMID- 1502015 TI - Pharmacological, toxicological and neurochemical effects of delta 2(E)-valproate in animals. AB - The E isomer of 2-ene-valproic acid (delta 2(E)-VPA) is the major active metabolite of the antiepileptic drug valproate (VPA) in various species, including humans. Experimental studies on delta 2(E)-VPA and VPA indicate that delta 2(E)-VPA may be a useful antiepileptic drug itself. delta 2(E)-VPA has the same wide spectrum of anticonvulsant activity as VPA with a somewhat higher anticonvulsant potency in rodent and dog models of different seizure types. As VPA, delta 2(E)-VPA increases presynaptic gamma-aminobutyric acid (GABA) levels in the brain, presumably by an effect on GABA synthesis and/or GABA degradation. delta 2(E)-VPA is a much more potent inhibitor of the human brain GABA-degrading enzyme than VPA. In high doses delta 2(E)-VPA is more sedative in rodents than is VPA; LD50 values are about the same. In mouse and rat models for teratogenicity, delta 2(E)-VPA does not induce teratogenic effects, whereas VPA is teratogenic in these models. Pilot rat studies on liver toxicity of VPA and VPA metabolites suggest that delta 2(E)-VPA is not hepatotoxic. In view of the rare but serious hepatotoxicity and teratogenicity of VPA in humans, delta 2(E)-VPA obviously merits interest as a valuable alternative drug in antiepileptic therapy. PMID- 1502016 TI - Delta 2-valproate biotransformation using human liver microsomal fractions. AB - The metabolism of 2-n-propyl-2-pentenoate (delta 2-VPA) was evaluated in human hepatic microsomal fractions. Two biotransformation pathways have been particularly investigated. In the presence of the cytochrome P-450 co-factor, NADPH, the main metabolites recovered were delta 3-VPA, delta 2,4-VPA and VPA. The glucuronidation of delta 2-VPA was also studied on various hepatic microsomal fractions using Brij 35 as activator and UDP-glucuronic acid as co-factor. A large interindividual variability occurred in this metabolic pathway. Km and Vmax were 0.85 mmol/l and 1.75 nmol.min-1.mg-1, respectively, for delta 2-VPA and 1.11 mmol/l and 5.71 nmol.min-1.mg-1 for VPA, respectively. The good correlation (r = 0.82; p less than 0.001) observed between the glucuronidation of VPA and delta 2 VPA as well as the mutual inhibition of each other's glucuronidation strongly suggests that (a) common single UDP-glucuronosyltransferase isoenzyme(s) was (were) involved in this glucuronidation step. The glucuronidation of specific substrates for various UDP-glucuronosyltransferase isoenzymes showed a good relationship between the glucuronidations of delta 2-VPA and morphine, a substrate for UDP-glucuronosyltransferase-2B. Moreover, morphine competitively inhibits delta 2-VPA glucuronidation. It seems the same isoenzyme or, at least, (a) very closely related isoenzyme(s) belonging to UDP-glucuronosyltransferase-2 isoenzyme, is involved in delta 2-VPA glucuronidation. PMID- 1502017 TI - Single-dose tolerance and pharmacokinetics of 2-n-propyl-2(E)-pentenoate (delta 2(E)-valproate) in healthy male volunteers. AB - 2-n-Propyl-2(E)-pentenoic acid (delta 2(E)-valproate) was administered to healthy volunteers in oral doses of 50-800 mg. The drug was tolerated well and no significant adverse effects were observed. Pharmacokinetic parameters were determined. Valproate and 3-keto-valproate were detected as metabolites. PMID- 1502019 TI - Enzymes involved in the metabolism of valproate. PMID- 1502018 TI - Studies on 2-n-propyl-2(E)-pentenoate (delta 2(E)-valproate) in man. PMID- 1502020 TI - Clinical Pharmacological Meeting. Gent, Belgium, 3 April 1992. Abstracts. PMID- 1502021 TI - A double-blind, placebo-controlled multicentre trial of ticlopidine in patients with peripheral arterial disease in Argentina. Design, organization and general characteristics of patients at entry. The EMATAP Group. AB - Patients with atherosclerotic disease of the lower limbs are at high risk of thrombotic events not only in the peripheral circulation, but also in the coronary and cerebral arteries. Ticlopidine, a potent inhibitor of platelet aggregation, can reduce the incidence of arterial thrombosis in patients suffering from intermittent claudication, as shown by a meta-analysis performed in 1987. In order to confirm these findings, we undertook a randomized, stratified, placebo-controlled, double-blind multicentre trial in Argentina in two parallel groups of patients suffering from intermittent claudication. Twenty one clinical centres participated in the trial and 615 patients were enrolled. Patients were eligible if they had presented obstructive arterial disease of the upper part of the lower limb (popliteal or above) for at least 12 months, confirmed by either angiography or Doppler studies, and intermittent claudication (stage II) assessed by treadmill testing. Non insulin treated diabetic patients were eligible if they fulfilled the other inclusion criteria and two strata, diabetic and non diabetic, were established. Patients enrolled were treated with either ticlopidine (500 mg/day) or placebo for 24 weeks. In this paper, we report the design and organization of the study and the baseline characteristics of the patient population at inclusion.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1502022 TI - Decreased G3PDH binding to erythrocyte membranes in sickle cell disease. AB - Several membrane abnormalities have been described in red cells from patients with sickle cell disease, responsible for chronic hemolytic anemia. We describe here a 35-50% inhibition of the binding of glyceraldehyde-3-phosphate dehydrogenase (G3PDH) to the membrane of sickle red cells. Varying the phosphorylation state of the membrane proteins did not change their affinity for the enzyme. Protein band 3 and the cytoplasmic domain of this protein isolated from sickle red cells showed normal interaction with the enzyme. The inhibition observed with intact membranes is not due to short term oxidation of membrane proteins, as various procedures inducing acute oxidative stress in normal membranes did not reproduce the inhibition of G3PDH binding. We conclude that the alteration of the binding of G3PDH to the membrane of sickle erythrocytes is probably related to long term processes involving cycles of HbS polymer formation. PMID- 1502023 TI - Age and sex matched analysis of Hb Lepore trait in a new population in Spain. AB - A group of subjects with Hb Lepore trait has been found in the region between Extremadura and Toledo in Spain. Clinical, radiological and hematological studies were carried out on 81 cases from 23 families. Asthenia was the sole complaint in seven of forty cases. Abdominal echography showed no cholelithiasis in 16 children under 16 years. Hb Lepore mean was 10.81 +/- 1.97%, range 6.5 to 16.1%, Hb A2 levels were normal and Hb F values were high. Globin chain synthesis in reticulocytes showed a total alpha/beta ratio of 1.89 +/- 0.3. Hematological values from Hb Lepore trait subjects were analyzed according to age and sex and the data compared to beta thalassemia and delta-beta thalassemia cases of matched age and sex. Hb Lepore trait patients had a milder form of thalassemia minor than beta thalassemia patients, with higher levels of hemoglobin, MCV and MCH for all three groups: children under 13 years, males over 14 years and females over 14 years. Children and females with Hb Lepore had higher hemoglobin levels than those with delta-beta thalassemia minor, while no significant difference was found in males. PMID- 1502024 TI - Chromosome studies in stimulated lymphocytes of 50 patients with B-cell chronic lymphocytic leukemia. AB - The chromosome constitutions of stimulated lymphocytes from 50 B-cell chronic lymphocytic leukemia patients were studied using different stimulation systems, i.e., TPA alone or associated with different cytokines. Adequate metaphases were obtained in 44 subjects (88%). Among 20 patients with abnormal karyotypes (45.5%), 7 had trisomy 12. The most frequent structural abnormality was a 14q+ resulting from translocations including one t(11;14) and two t(14;17), while deletions on the long arms of chromosomes 6 and 13 constituted a second common alteration. The most important finding in this series was the recurrence of a t(18;22) observed in two cases. PMID- 1502025 TI - Inhibition of human endothelial cell growth by human monocytes in coculture. AB - Previous studies conducted in different experimental models have shown that human monocytes (Mo) possess both stimulating and inhibiting factors for endothelial cell growth. Since Mo are frequently found in the vicinity of endothelial cells, we examined the direct effect of human peripheral blood Mo on the proliferation of human umbilical vein endothelial cells (HEC) in in vitro culture systems. Mo obtained either by counter centrifugation elutriation or by selective adhesion on gelatin-autologous plasma or purified fibronectin coated plastic surfaces inhibited HEC growth as determined by HEC count or 3H-methyl thymidine incorporation. This growth inhibitory effect was dependent on the number of monocytes: 50% inhibition of 3H-thymidine uptake by HEC was achieved for a Mo-EC ratio of 1:4. Mo isolation by selective adhesion on gelatin-plasma resulted in a significantly higher inhibitory effect (p less than 0.02) than that observed with Mo isolated on fibronectin coated surfaces or by elutriation techniques, suggesting a possible stimulation of Mo by contact with gelatin-plasma. Endothelial cell growth factor plus heparin did not reverse this inhibition of HEC growth. Results obtained in diffusion chamber and coculture systems showed that soluble products of Mo origin can inhibit HEC proliferation but the inhibition was greater when Mo and HEC were in contact. The effect was not due to cytotoxicity as evaluated by cell counting and 51Chromium release from HEC. These in vitro results suggest that normal monocytes could exert a regulatory role on the proliferation of endothelial cells. PMID- 1502026 TI - Streptococcal bacteremia in neutropenic adult patients. AB - In order to define the circumstances of occurrence, clinical presentation and prognostic factors of streptococcal bacteremia in neutropenic patients, we retrospectively reviewed 60 cases of streptococcal bacteremia following intensive chemotherapy for acute myeloblastic leukemia (AML), acute lymphoblastic leukemia (ALL) or allogeneic bone marrow transplantation. Causative streptococcal species included streptococcus viridans (42 cases), streptococcus faecalis (12), streptococcus pneumoniae (4) and other streptococci (2). All patients were febrile and 32% presented diffuse pneumopathy with frequent isolation of streptococci from bronchoalveolar washing fluids. There were no statistical differences in presentation between the bacteremia caused by different streptococcal species. Death occurred in 22% of the patients and factors favoring poor prognosis included pneumopathy (p less than 0.001), more than 2 positive blood cultures (p less than 0.01) and initial chemotherapy for AML (p less than 0.01). Pneumopathy occurred more frequently after chemotherapy for AML. It is concluded that streptococcal bacteremia is to be prevented in patients undergoing intensive chemotherapy, particularly if cytarabine is used. PMID- 1502027 TI - A national Italian survey in hemocytometry: first year report. AB - The paper presents the results of the first year of an Italian nation wide quality control programme for hemocytometric tests, involving public laboratories and concerning the following parameters: hemoglobin, erythrocytes, leukocytes (nucleated cells), mean corpuscular volume, platelets and hematocrit. Results are compared principally with those obtained from the French national programme owing to the use of identical blood standards. PMID- 1502028 TI - Plasma prekallikrein, coagulation and fibrinolytic parameters in myeloma patients. AB - Plasmatic prekallikrein, factor XII, factor XI, C1-inactivator and alpha 2 macroglobulin were evaluated in myeloma patients. Results suggest no modification in the contact phase since there was no significant difference between patients and controls. Other parameters of blood coagulation and fibrinolysis (APTT, TT, fibrinogen, factor V, ELT and LAFP) gave findings consistent with those described in the literature. PMID- 1502029 TI - Evaluation of the erythrocyte and platelet morphological analysis given by the hematology analyzer Coulter STKS. AB - The morphological profiles of red blood cells (RBC) and platelets (Plt) derived from the distribution analysis given by the Coulter STKS were evaluated in two groups of patients suffering from non hematological (n = 293) and hematological (n = 257) conditions. The RBC and Plt flags were studied in terms of sensitivity of the morphological analysis and specificity and significance of each flag. When all RBC and Plt flags were considered, the percentages of false negatives and false positives in our subjects were found to be 4.7% and 13.4% respectively, with a global efficiency of 81.8%. The sensitivity of the alarm system was higher than 90% for all types of abnormality, except microcytosis (81%) and Howell-Jolly bodies (57% over a limited number of 7 cases). The specificity of the STKS response was found to be low except for anisocytosis (88.5%) and macrocytosis (86.1%). It was shown that the flags microcytosis and/or hypochromia and macrocytosis were poorly significant when they appeared in isolation (false positive rates of 86.6% and 84.2% respectively). Thus, these alarms could be eliminated from the review criteria. When considering only the flags anisocytosis, NRBCs, micro RBCs/RBC fragments, dimorphic RBC pop, PLT clumps and giant Plt, the percentage of false positives was 8.1%. However, it must be kept in mind that suspect leucocyte flags remained review criteria, resulting in a final false negative rate of 2.5% for RBC and Plt morphological abnormalities. PMID- 1502030 TI - Malignant melanoma and hairy cell leukemia. Two cases. AB - The authors report two cases of malignant melanoma associated with hairy cell leukemia. Skin neoplasia preceded hematological malignancy in the first observation. Among reports concerning the association of malignant melanoma with hematological diseases, chronic lymphocytic leukemia, Hodgkin's lymphoma and non Hodgkin's lymphoma are preponderant. Epidemiological studies would be of value to predict the expected risk of malignant melanoma in hairy cell leukemia. PMID- 1502031 TI - Juvenile chronic myelocytic leukemia with unusual cytogenetic clonal evolution. AB - Cytogenetic studies are reported in a case of juvenile chronic myelocytic leukemia with dysmyelopoiesis and skin involvement. The clonal evolution of a 6q anomaly is described. Hematological and cytogenetic findings suggest a role of hematopoietic stem cell in this patient for whom the outcome was fatal. PMID- 1502032 TI - Malignant thymic lymphoblastic lymphoma and myasthenia gravis: an exceptional association. AB - Thymic lymphoblastic lymphoma and myasthenia gravis rarely coexist. Only two cases have been reported and we describe here a third case. A 60 year old man presented a typical history of myasthenia gravis, confirmed by neurological investigations including electromyography. Chest X-ray revealed an anterior mediastinal tumor. At thoracotomy, a 60 mm mass adherent to the pericardium was excised and a lymphoblastic lymphoma was diagnosed. The lymphogram showed enlarged pelvic and abdominal lymph nodes consistent with lymphoma. A m-BACOD chemotherapy regimen gave rapid and complete remission of both lymphoma and myasthenia gravis and the patient is now alive 25 months after the start of chemotherapy with no evidence of disease. PMID- 1502033 TI - No doctor in the house. PMID- 1502034 TI - Inappropriate support. PMID- 1502035 TI - Future trends. PMID- 1502036 TI - Everyone's problem. PMID- 1502037 TI - A whiff of reality. PMID- 1502038 TI - A ban for all seasons. PMID- 1502039 TI - The facts behind the smoking argument. PMID- 1502040 TI - On the receiving end. PMID- 1502041 TI - James and Sarah. PMID- 1502042 TI - Team spirit. PMID- 1502043 TI - Higher aims. PMID- 1502044 TI - A rare event. PMID- 1502045 TI - Systems of life. Muscle 3. PMID- 1502046 TI - Gauging outpatient satisfaction. PMID- 1502047 TI - Primary nursing. Keeping it going. PMID- 1502048 TI - Primary nursing. The heart of communication. PMID- 1502049 TI - Pioneer spirit. PMID- 1502050 TI - A healthy nation? PMID- 1502051 TI - Social development. PMID- 1502052 TI - Brain waves. PMID- 1502053 TI - The price of health. PMID- 1502054 TI - Hard sell? PMID- 1502055 TI - Patients' choice. PMID- 1502056 TI - Fed up? PMID- 1502057 TI - Sorting out triage. PMID- 1502059 TI - Dogged determination. PMID- 1502058 TI - Understanding dyspraxia. PMID- 1502060 TI - Adult education. PMID- 1502061 TI - Teaching what comes naturally. PMID- 1502062 TI - Responding to aggression. PMID- 1502063 TI - Learners' shifting images of nursing. PMID- 1502064 TI - Mixed feelings. PMID- 1502066 TI - Sore points. PMID- 1502065 TI - Finding the limits. PMID- 1502067 TI - A good death. PMID- 1502068 TI - Cutting edge. PMID- 1502069 TI - Pressing problem. PMID- 1502070 TI - Vital ingredient. Interview by Claire Laurent. PMID- 1502071 TI - Everything shipshape? PMID- 1502072 TI - The pursuit of excellence. PMID- 1502073 TI - Protecting the species. PMID- 1502074 TI - Who will pay for PREP? PMID- 1502075 TI - Understanding compound drugs. PMID- 1502076 TI - Assessing health needs and measuring patient satisfaction. AB - This paper describes two aspects of the NHS reforms--an emphasis on needs assessment and patient satisfaction. The latter is illustrated with reference to day surgery. PMID- 1502077 TI - Back to nature. PMID- 1502078 TI - Planning the future. PMID- 1502079 TI - Labouring in comfort. PMID- 1502080 TI - Helping Billy move on. PMID- 1502081 TI - French lessons. PMID- 1502082 TI - Focusing on solutions. PMID- 1502083 TI - From Pompeii to the present. PMID- 1502084 TI - Material benefits. PMID- 1502085 TI - Attitude problems. PMID- 1502086 TI - Pulling together. PMID- 1502087 TI - ECT use sign of problems. PMID- 1502088 TI - The gentle touch. PMID- 1502089 TI - Out of the shadows. PMID- 1502090 TI - A job for sister? PMID- 1502091 TI - Mixed blessings. PMID- 1502093 TI - Coming of age. PMID- 1502092 TI - Unequal struggle. PMID- 1502094 TI - Managing the boundaries. PMID- 1502095 TI - Baby milks and the EC. Infant nutrition. PMID- 1502096 TI - Weaning without sugar. Infant nutrition. PMID- 1502097 TI - The home team. Mental health. PMID- 1502098 TI - A critical response. PMID- 1502100 TI - Making sense of pulse oximetry. PMID- 1502099 TI - Education. The clinical nurse tutor debate. PMID- 1502101 TI - Yes, Minister! History. PMID- 1502102 TI - Finding the key. Nursing narratives. PMID- 1502103 TI - A special relationship. Nursing narratives. PMID- 1502104 TI - Attending the spirit. Nursing narratives. PMID- 1502105 TI - Lifting the mask. PMID- 1502106 TI - Which lavender oil? Complementary therapies. PMID- 1502107 TI - Can nurses do their sums? PMID- 1502108 TI - Computing--getting into the system. PMID- 1502109 TI - Evaluation of the effects of orthodontic pacifiers on the primary dentitions of 24- to 59-month-old children: preliminary study. AB - This study was designed to compare the occlusions of 24- to 59-month-old children who used orthodontic or conventional pacifiers to the occlusions of a group of controls who had no sucking habits. Information on the habits was collected by parental questionnaires. Ninety-five children were examined for malocclusions involving overbite, overjet, canine, and molar relationships, and posterior crossbites. Users of orthodontic pacifiers had statistically significantly greater overjets, and there was a significantly higher proportion of subjects with open bite in the conventional pacifier group. There was a trend toward a greater number of subjects in the control and orthodontic pacifier group with overbites less than or equal to 50%. These differences were not clinically significant, however. There appeared to be only minor differences between the occlusions of the two pacifier groups. PMID- 1502110 TI - The effects of various dental procedures and patient behaviors upon nitrous oxide scavenger effectiveness. AB - This prospective study of 36 children, ages 44-93 months, receiving nitrous oxide oxygen under standardized conditions during routine dental procedures was conducted to determine what influence eight selected dental procedures and three patient behaviors had on ambient nitrous oxide (N2O) levels in the dentist's breathing zone. Half the children received nitrous oxide-oxygen via a scavenging nasal mask. An infrared spectrophotometer analyzed the ambient N2O level continuously throughout the procedure and the time-weighted average (TWA) for consecutive 15-sec intervals was recorded by a microprocessor. A video camera was used to synchronize the coded dental procedures and patient behaviors to the TWA ambient N2O levels recorded. The results demonstrated that scavenging significantly reduced the dentist's exposure to ambient N2O (P less than 0.05, nonscavenged mean = 284.7 ppm; scavenged mean = 36.6 ppm), but the mean TWA N2O concentration remained significantly higher, P less than 0.05, than the 25-ppm level recommended by the National Institute for Occupational Safety and Health (NIOSH). Supplemental oral evacuation was the only dental procedure capable of reducing ambient N2O to below NIOSH's recommendation when scavenging was employed. The administration of local anesthesia consistently created a significant increase in ambient N2O levels. Patient behaviors of talking, crying, and movement also resulted in significant increases from baseline ambient N2O levels. PMID- 1502111 TI - Dental caries in relation to nutritional stress in early English child populations. AB - This research studied an association between dental caries prevalence in the primary dentition and cribra orbitale, an indicator of nutritional stress in archeological populations. Skeletal remains of 221 British children (Pre-Roman to Late Medieval) were examined, of whom 100 had orbital material available. Dental caries, as dmfs, was related to the presence of cribra orbitale (none, slight, moderate, or severe). Thus, data for 50 children showed a statistically significant association (P less than 0.005) between caries prevalence and cribra orbitale using the Fisher Exact Test, suggesting that nutritional stress is an associated factor in caries etiology in children. PMID- 1502112 TI - Frequency of alveolar bone loss adjacent to proximal caries in the primary molars and healing due to restoration of the teeth. AB - The frequency of alveolar bone loss adjacent to extensive proximal caries, and the effect of dental restorations on alveolar bone loss and healthy alveolar bone were examined in human primary molars. Proximal caries, contact loss, mesial drift and the presence of alveolar bone loss were recorded from 190 bite-wing radiographs from 60 boys and 46 girls. Proximal caries was evident in 297 quadrants. In 63.0% of quadrants, both primary molars had proximal caries. Contact loss was evident in 38.4% of the quadrants with proximal caries. Bone loss was found in 12.1% of the quadrants with proximal caries or 31.6% of those with contact loss. Analysis of variance for the presence of bone loss indicated statistically significant values (P less than 0.05) for one or two teeth with caries by quadrant, the presence or absence of contact loss, and age. A second examination was available for 41 children. Among these, eight out of the 36 bone defects disclosed at the first examination were present. At the second examination, after tooth restoration, healing of five bone defects was evident. These findings indicate a connection between the presence and treatment of extensive proximal caries and alveolar bone health in the primary dentition. PMID- 1502113 TI - Class IV preparation design for microfilled and macrofilled composite resin. AB - The current standard preparation for Class IV composite restorations is the placement of a bevel on all enamel margins. This study evaluated chamfered and beveled preparations for Class IV restorations of lesions with microfilled and macrofilled composite resin. Forty incisors were obtained and standardized lesions for Class IV restorations were formed. Twenty teeth had a 1.5-mm bevel placed and 20 had a 1.5-mm chamfered preparation placed. Half of the beveled and chamfered preparations were restored with microfilled composite resin; the remaining were restored with macrofilled composite resin. All restorations were fractured with an Instron Testing Machine. The mean force (lbs +/- SD) to fracture the restorations were: (beveled, microfilled composite 16.0 +/- 4.4); (chamfered, microfilled composite 30.6 +/- 20.0); (beveled, macrofilled composite 34.9 +/- 18.6); (chamfered, macrofilled composite 48.8 +/- 14.3). The chamfered preparations provided greater restoration fracture resistance than beveled preparations, for both microfilled and macrofilled composite restorations. Scheffe's test indicated traditional beveled, microfilled Class IV composite resin restorations significantly decreased fracture resistance compared to chamfered, macrofilled composite restorations (P less than 0.001). PMID- 1502114 TI - Influence of vitamins and iron on plasma fluoride levels in rats. AB - Thirty female Sprague-Dawley rats (250 +/- 10 g) were divided randomly into five equal groups. After overnight fasting, a silastic catheter was placed in the jugular vein of each rat. Each group was intragastrically administered 0.25 mg F/250 g rat weight in 1 ml of one of the following forms of fluoride supplements: Pediaflor (Abbott/Ross, Columbus, OH), Tri-Vi-Flor, Tri-Vi-Flor + iron; Poly-Vi Flor or Poly-Vi-Flor + iron (Mead Johnson Nutritionals, Bristol-Myers Squibb Co., Evansville, IN). Timed blood samples were collected and plasma fluoride concentration was determined using the microdiffusion method. The presence of iron and vitamins affect the bioavailability of fluoride as measured by the area under the time-plasma fluoride concentration curve. PMID- 1502115 TI - Use of a bonding agent to reduce sealant sensitivity to moisture contamination: an in vitro study. AB - Moisture contamination of etched enamel during application of sealant is the most frequently cited reason for sealant failure. In preliminary studies, a dentin bonding agent (Scotchbond Dual Cure, 3M, St. Paul, MN) has been shown to bond adequately to etched enamel after salivary contamination. This study investigated bond strength in vitro, when a bonding agent was used beneath sealants under varied conditions of contamination. Five hundred bovine incisor crowns were separated randomly into eight groups. The enamel samples, etched for 60 sec with a 37% phosphoric acid gel, were contaminated with: 1) fresh whole saliva, air dried, 2) fresh whole saliva, left wet, or 3) moisture from a humidity chamber. All contamination conditions were tested for sealant bond strength with and without the bonding agent as an intermediate layer under the sealant. As controls, both sealant and bonding agent under sealant also were applied to clean etched enamel. Bond strength was measured using a universal testing machine. Data were analyzed using a two-way ANOVA. Under conditions of humidity or intact saliva, sealant alone showed significant reduction in bond strength (P less than 0.001). Bonding agent under sealant on wet contamination yielded bond strengths equivalent to the bond strength obtained when sealant was bonded directly to clean, etched enamel. Bonding agent used without contamination yielded bond strengths significantly greater than the bond strength obtained when using sealant alone without contamination (P less than 0.001). When the saliva was air dried onto the surface, there was no significant difference in bond strengths whether or not a bonding agent was used under the sealant. PMID- 1502116 TI - Comparison of colorimeter and electrode analysis of water fluoride. PMID- 1502117 TI - Effect of prophylaxis agents on the shear bond strength of a fissure sealant. PMID- 1502118 TI - Shell teeth--management from the mixed to the permanent dentition: case report. PMID- 1502119 TI - Bilateral double primary molars: case report. PMID- 1502120 TI - Anatomy of primary incisor and molar root canals. PMID- 1502121 TI - Enamel defects of the primary dentition and osteopenia of prematurity. PMID- 1502122 TI - Nutritional value of some non-conventional plant foods of India. AB - Thirteen non-conventional foods including fruits, leaves and grains consumed in various parts of the Indian subcontinent were analysed for their nutritional value. Khejri beans (Prsopsis cineria), Pinju (Capparis decidua) and Kachri (Cucumis species) contained considerable amounts of protein (15-18%). Kachri was rich in fat (13%). Bhakri (Tribulus terristris), Gullar (Ficus glomerata) and Peehl (Salvadora oleoides) were found to be rich sources of calcium; Gullar contained about 15 times the amount of calcium present in wheat. Phosphorus content of Santhi (Boernavia diffusa), Khejri beans, Bhakri, Pinju and Lehsora (Cordia dichotoma) were noticeable. Zinc was present in high amounts in Peepalbanti (Ficus religiosa) and Gullar; as was iron in Santhi and Bhakri and manganese in Santhi. Besides iron, zinc and calcium, Pinju contained appreciable amounts of beta-carotene and vitamin C. However, Santhi contained high amounts of oxalic acid. PMID- 1502123 TI - Physico-chemical composition and characterisation of the seed and seed oil of Sclerocarya birrea. AB - The physicochemical composition of Sclerocarya birrea was assessed by standard methods and was found to contain 11.0% Crude oil, 17.2% Carbohydrate, 36.70% Crude protein 3.4% fibre and 0.9% crude saponins. The fatty acid distribution in the seed oil was obtained by fractionating the volatised fatty acid by GC-MS. The oil is made up of nine fatty acids of which palmitic, stearic and arachidonic acids are the most dominant. PMID- 1502124 TI - The effect of fermentation on the nutrient status and on some toxic components of Icacinia manni. AB - The effect of fermentation on the nutrient status and on some toxic components of Icacinia manni was investigated. Chemical analysis of both unfermented and fermented products revealed an increase in protein, ash and fibre content while the lipid and carbohydrate content showed a decrease. The results indicated that fermentation resulted in protein enrichment of the fermented Icacinia manni mash. Fermentation was also observed to cause a marked decrease in the level of some toxic components (oxalic acid, phytic acid and hydrocyanic acid) of the product. The possibility of incorporating Icacinia manni among the edible starchy plant tubers is discussed. PMID- 1502125 TI - Protein quality of developed home made weaning foods. AB - Home made weaning foods developed from locally available foods like bajra, barley, green gram (Vigna radiata L.), amaranth grain (Amaranthus sp.) and jaggery using household technologies like roasting and malting had a PER ranging from 2.04 to 2.13, BV 79.56 to 80.68, NPU 66.75 to 67.86, NPR 2.13 to 2.76 and PRE 34.18 to 44.18. The values were comparable to that of cerelac--a commercial weaning food. PMID- 1502126 TI - The nutritive quality of sorghum-commonbean tempe. AB - The nutritive quality of sorghum-commonbean (40:60) tempe manufactured by Rhizopus oligosporus: Rhizopus oryzae (1:1) mixed culture fermentation was determined. The protein, crude fat and ash content increased slightly, while carbohydrates decreased. The dietary fibre of the tempe increased by 10%. Mould fermentation increased the content of reducing sugars, total acid and aminonitrogen 15.3, 6.7 and 4.6-fold, respectively. It decreased the phytate content by 44% and it increased the tannic acid content by 52%. In vitro iron absorption increased from 2.8 to 12.5%. The protein efficiency ratio of tempe was 1.61 +/- 0.33; the net protein ratio was 2.39 +/- 0.20; the in vitro and in vivo protein digestibility were 88.2 and 80.0 +/- 0.05% respectively, while the protein efficiency ratio, net protein ratio in vivo digestibility of skim milk was 2.96 +/- 0.17, 3.51 +/- 0.17 and 98.0 +/- 1.87, respectively. The sorghum bean tempe could be used for supplementary feeding. PMID- 1502127 TI - Certain functional properties of defatted pumpkin seed flour. AB - Defatted pumpkin (C. pepo and C. maxima) seed flour has potential food uses because of its high protein content, 61.4 +/- 2.56%. The functional and electrophoretic properties of the defatted flour were investigated. Polyacrylamide gel electrophoresis and electrofocusing indicated 14 bands of water-soluble protein subunits with isoelectric points between 3.81-8.08 and apparent molecular weights between 19,200 and 97,000 daltons. Minimum nitrogen solubility was observed at pH values between 3.0-7.0 and exceeded 90% at pH above 9.0. Solubility was a function of ionic strength. It appeared that, even at the pH of minimum solubility, the pumpkin seed proteins could be dissolved up to high concentrations by increasing NaCl molarity. The viscosity of flour-water dispersion was affected by flour and salt concentrations, and temperature. The least gelation concentration was 8% (w/v) and the water and oil absorption 24.8 +/- 2.03 and 84.4 +/- 4.05 g/100 g respectively. Sorption isotherms, BET monolayer moisture and binding energy of sorption were also calculated. Both foam capacity and stability were pH dependent. PMID- 1502128 TI - In vitro enzymatic hydrolysis of protein and protein pattern change of soya and faba beans during germination. AB - In addition to technological processes like heat treatment, germination can be an alternative process for the improvement of protein quality of legumes. This was demonstrated by enzymatic protein hydrolysis of flour of germinated faba and soya beans, using a pepsin-pancreatin enzyme system. SDS-PAGE was used to study the changes in protein pattern of these legumes during germination. In addition, the effect of germination on the content of condensed tannins in flour from germinated faba beans and trypsin inhibitors in flour from germinated soya beans were studied. Germination for five days resulted in a maximum increase in enzymatic protein hydrolysis by 21.3% in flour from faba beans and by 25.7% in flour from soya beans after 12 hours of germination. Protein patterns, obtained with SDS-PAGE demonstrated a considerable protein breakdown during germination between day 2 and 3 in faba beans and between day 1 and 2 in soya beans. The tannin content in flour from faba beans decreased by 29.7% after seven days of germination, but the tannin content of the hulls of the faba beans did not change during that period of germination. The trypsin inhibitors in flour from soya beans decreased by 25.5% after seven days of germination. We conclude that the increased enzymatic hydrolysis of protein in both legumes cannot be explained by a decrease of tannins or trypsin inhibitors. The possible explanation is that through degradation of proteins during germination of the legumes, the cleaved protein fragments are more susceptible for hydrolysis by pepsin-pancreatin. PMID- 1502129 TI - Major U-turn on 13.8% pay cut, but for how long? PMID- 1502130 TI - Hobson's (dental) choice: going private, going grey or going under? PMID- 1502131 TI - NHS pensions give good benefits but not a panacea for all GDPs. PMID- 1502132 TI - Electronic dental anaesthesia review. PMID- 1502133 TI - Current topic: comparative physiology of placental oxygen transport. AB - Development of knowledge about placental O2 transport (PO2) is discussed by focusing attention on the factors that determine umbilical venous PO2. In near term pregnant sheep umbilical venous PO2 is much lower than maternal arterial PO2 and is about 20 torr lower than uterine venous PO2 in ewes who are the homozygous carriers of low O2 affinity ovine hemoglobin. Experimental evidence points to two main reasons for the low umbilical venous PO2 of sheep: (a) the uterine and umbilical circulations form an ineffective venous equilibration exchanger, and (b) a large uterine-umbilical venous PO2 gradient is required to draw O2 across a placental barrier which has a small O2 diffusing capacity relative to placental and fetal O2 demand and relative to the ineffective perfusion pattern. The latter explanation contradicts theoretical models which represent placental O2 transport as virtually 100 per cent blood flow limited. In near-term rabbits and guinea pigs umbilical venous PO2 is also quite low, but for different reasons. In these species, the uterine and umbilical circulations form a countercurrent exchanger which allows the mother to perfuse the uterus at a very low rate. The effectiveness of countercurrent exchange is exploited to decrease the demand of pregnancy on the maternal circulation, rather than to increase the level of fetal oxygenation. There is suggestive, as yet inconclusive, evidence suggesting that in some species, notably the domestic cat, placental countercurrent exchange is combined with a low O2 affinity maternal hemoglobin and a sufficiently high uterine blood flow to produce a high level of umbilical venous PO2. The striking diversity and complexity of data about placental O2 transport demands great caution in applying comparative knowledge to the human placenta. Experimental evidence seems to indicate that the near-term human placenta is a venous equilibration exchanger, but the information which is presently available is inadequate for a firm conclusion. PMID- 1502134 TI - Current topic: proteolysis in the penetration phase of the implantation process. PMID- 1502135 TI - Ultrastructural evidence for transtrophoblastic channels in the hemomonochorial placenta of the degu (Octodon degus). PMID- 1502136 TI - Expression of transferrin receptors during differentiation of human placental trophoblast cells in vitro. AB - In most cell types, transferrin receptor expression is correlated with the proliferation rate, being increased by growth stimulation, or decreased by induction of terminal differentiation. In the human placenta the multinucleated syncytiotrophoblast, in direct contact with maternal blood, is derived by differentiation from mononucleated cytotrophoblast. In this study we examined changes in transferrin receptor expression during in vitro differentiation of trophoblast. Cells cultured in Ham's/Waymouth's medium (HWM) remained primarily mononuclear throughout the study, whereas incubation in keratinocyte growth medium (KGM) led to formation of multinucleate masses within 2-3 days of culture. Cell surface binding of 125I-labelled transferrin increased fivefold between days 1-5 of culture in both media and surface receptors were saturated at 7-14 micrograms/ml (90-200 fM). At saturation, the amount of transferrin bound to syncytiotrophoblast was 37 per cent lower than in cytotrophoblast. Scatchard analysis revealed a reduction in the number of surface transferrin receptors in syncytiotrophoblast compared to cytotrophoblast. A corresponding 29 per cent reduction in the binding of transferrin to intracellular sites was observed in syncytiotrophoblast. Distribution of receptors between surface and intracellular sites was therefore similar in both cytotrophoblast and syncytiotrophoblast. The affinity of transferrin for transferrin receptors was 3.7-fold higher in syncytiotrophoblast when compared to cytotrophoblast. Observed differences between the two cell types were not due to the presence of growth factors or higher iron levels in KGM. Expression of a high number of surface transferrin receptors in syncytiotrophoblast (1.5 x 10(12)/mg protein), along with a high affinity of these receptors for iron-saturated transferrin, could help explain the efficient transport of large amounts of iron from mother to fetus. PMID- 1502137 TI - Multiple forms of rat placental lactogen-II (rPL-II): purification and partial characterization of rPL-II. AB - The present study was designed to develop a procedure for purifying rPL-II and a homologous radioimmunoassay (RIA) for rPL-II. Molecular profiles of rPL-II were also investigated in tissue and plasma. rPL-II was purified 3,780-fold, based on its radioreceptor assay (RRA) activity compared to ovine prolactin (0PRL), from the placenta of day 18 pregnant rats using ammonium sulfate precipitation and chromatography on phenyl-Sepharose, DEAE-TOYOPEARL 650S, AF-chelate TOYOPEARL 650M and Sephadex G-100. Electrophoretic analysis on SDS gel revealed molecular weight heterogeneity of purified rPL-II, which consisted of three proteins; a major form with a molecular weight of 20.0 K and two minor forms with molecular weights of 20.6 K and 21.0 K under non-reducing conditions. One of the minor forms of rPL-II observed under non-reducing conditions disappeared with 2 mercaptoethanol treatment and the rest of the hormones migrated as 24.5 K and 25.0 K molecular weight species, suggesting that it is a cleaved form of rPL-II. Purified rPL-II displaced 125I-labelled oPRL from binding sites on rabbit mammary gland membranes in a dose-dependent manner. rPL-II and rPRL were, respectively, 21 and 2 per cent as effective as oPRL in the displacement. Antibody to purified rPL-II was raised in rabbits and a homologous RIA for rPL-II was developed. No displacement was observed with rPRL, rGH, oPRL, and other pituitary hormones up to 1,000 ng/ml. Molecular profiles of rPL-II in the placental tissue and plasma from day 18 pregnant rats were examined by gel chromatography on Sepharcryl S-300 HR and by Western blotting. Chromatography of the placental extracts revealed a single peak, which accounted for 86 per cent of the total RIA activity. Anti-rPL II antiserum detected proteins of at least three molecular sizes as monomeric forms with molecular weights of 20.0, 20.6, and 21.0 K in the non-reducing placental extracts. One of them disappeared with 2-mercaptoethanol treatment and other two proteins had molecular weights of 24.5 and 25.0 K, indicating monomeric heterogeneity of rPL-II in the tissue. The elution profile of day 18 plasma in RIA activity gave two major peaks; the first, eluting just after the void volume (approximate molecular weight of 530 K) accounted for 35 per cent of the total RIA activity, and the second coinciding with the same elution volume as the monomeric form in the placental extract constituted about 26 per cent of the total RIA activity.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1502138 TI - Chorionic peptidase inactivates GnRH as a post-proline peptidase. AB - Recently, we have described a chorionic peptidase (C-ase-1) which inactivates gonadotropin releasing hormone (GnRH), oxytocin, angiotensin II and thyrotropin releasing hormone. Since all these hormones contain a proline residue, we proposed that C-ase-1 may act as a post-proline peptidase. Using HPLC and amino acid analyses, we have defined the products which resulted from enzymatic inactivation of GnRH by C-ase-1. The N-terminal nonapeptide of GnRH was isolated by HPLC and confirmed by amino acid composition analyses. Thus, it was demonstrated that C-ase-1 acts as a post-proline peptidase when inactivating GnRH, yielding the nonapeptide, i.e., des-Gly10-NH2-GnRH, and Gly-NH2. The levels of intrauterine GnRH, angiotensin II, oxytocin and thyrotropin releasing hormone may be affected and integrated by this enzyme. Thus, C-ase-1 may play an important role in the regulation of the paracrine and endocrine function during pregnancy. PMID- 1502139 TI - Decidual inflammation in villitis of unknown aetiology. PMID- 1502140 TI - Classics revisited: Joseph Needham: 'Chemical Embryology'--Cambridge 1931. PMID- 1502141 TI - Overexpressed full-length human BCL2 extends the survival of baculovirus-infected Sf9 insect cells. AB - Full-length and truncated human BCL2 lacking the entire C-terminal hydrophobic domain have been overexpressed in Spodoptera frugiperda insect cells with the baculovirus expression system. Immunoblot analysis with BCL2-specific antibodies revealed that both full-length and truncated BCL2 are expressed as multiple immunoreactive species, suggesting posttranslational modifications. The expression of the full-length but not the truncated BCL2 extended the survival of baculovirus-infected cells by preventing virus-induced DNA cleavage. This result is consistent with the reported protective effect of BCL2 against apoptosis in mammalian lymphocytes and suggests a conserved function in evolution. Subcellular fractionation and indirect immunofluorescence studies in intact cells demonstrated that the recombinant full-length and truncated BCL2 proteins were expressed predominantly as nuclear membrane-associated proteins. These results imply that BCL2 must utilize hydrophobic domains other than the deleted domain for its association with the subcellular membranes. Metabolic labeling of insect cells expressing the full-length and the truncated form of BCL2 with 32P(i) demonstrated that BCL2 is a phosphoprotein. PMID- 1502142 TI - Evolution of consciousness. AB - The hypothesis of the origin of consciousness is built upon the unique properties of the mammalian neocortex. The apical dendrites of the pyramidal cells bundle together as they ascend to lamina I to form neural receptor units of approximately 100 apical dendrites plus branches receiving hundreds of thousands of excitatory synapses, the collective assemblage being called a dendron. It is proposed that the whole world of consciousness, the mental world, is microgranular, with mental units called psychons, and that in mind-brain interaction one psychon is linked to one dendron through quantum physics. The hypothesis is that in mammalian evolution dendrons evolved for more effective integration of the increased complexity of sensory inputs. These evolved dendrons had the capacity for interacting with psychons that came to exist, so forming the mental world and giving the mammal conscious experiences. In Darwinian evolution, consciousness would have occurred initially some 200 million years ago in relation to the primitive cerebral cortices of evolving mammals. It would give global experiences of a surrounding world for guiding behavior beyond what is given by the unconscious operation of sensory cortical areas per se. So conscious experiences would give mammals evolutionary advantage over the reptiles, which lack a neocortex giving consciousness. The Wulst of the avian brain needs further investigation to discover how it could give birds the consciousness that they seem to have. PMID- 1502143 TI - Dual role of the nucleolar transcription factor UBF: trans-activator and antirepressor. AB - In a reconstituted system consisting of partially purified RNA polymerase I (pol I) and the initiation factors TIF-IA, TIF-IB, and TIF-IC, the nucleolar factor UBF (upstream binding factor) stimulates transcription from the rRNA-encoding DNA (rDNA) promoter at least 50-fold. This activation is not observed at high template concentrations or in the presence of highly purified pol I. Template commitment experiments suggest that UBF activates transcription by relieving inhibition exerted by a negative-acting factor(s) in the polymerase fraction that competes for TIF-IB binding to the rDNA promoter and prevents the formation of preinitiation complexes. Using purified histone H1 bound to DNA as a model for the repressed state of the rDNA promoter, we show that UBF counteracts H1 mediated repression of pol I transcription. The implications of these findings are discussed with respect to the protein-protein and protein-DNA interactions at the rDNA promoter and the possible involvement of UBF in control of ribosomal gene transcription. PMID- 1502144 TI - Toward rules relating zinc finger protein sequences and DNA binding site preferences. AB - Zinc finger proteins of the Cys2-His2 type consist of tandem arrays of domains, where each domain appears to contact three adjacent base pairs of DNA through three key residues. We have designed and prepared a series of variants of the central zinc finger within the DNA binding domain of Sp1 by using information from an analysis of a large data base of zinc finger protein sequences. Through systematic variations at two of the three contact positions (underlined), relatively specific recognition of sequences of the form 5'-GGGGN(G or T)GGG-3' has been achieved. These results provide the basis for rules that may develop into a code that will allow the design of zinc finger proteins with preselected DNA site specificity. PMID- 1502145 TI - Spatial pattern of cdc2 expression in relation to meristem activity and cell proliferation during plant development. AB - The p34 protein kinase encoded by the cdc2 gene is a key component of the eukaryotic cell cycle required for the G1- to S-phase transition and entry into mitosis. To study the regulation of plant meristem activity and cell proliferation, we have examined the tissue-specific accumulation of cdc2 transcripts in Arabidopsis thaliana and the related crucifer radish (Raphanus sativus) by in situ hybridization using A. thaliana cdc2 cDNA sequences as a probe. cdc2 transcripts accumulated in leaf primordia and within the vegetative shoot apical meristem. During flower development, high levels of expression were observed in meristems, in the basal regions of developing organs, in the developing vasculature, and associated with rib meristems elaborated late in the development of some floral organs. In root tips, cdc2 transcripts accumulated in the meristematic region and adjacent daughter cells but were not detected in the quiescent center. There was strong hybridization throughout the pericycle, and a further localized accumulation of cdc2 transcripts was observed in the initial stages of the activation of a new meristem at sites of lateral root development. We conclude that cdc2 expression is a critical factor in the regulation of meristem activity and establishment of proliferative competence. PMID- 1502146 TI - Development of a quasispecies of human immunodeficiency virus type 1 in vivo. AB - During treatment with one specific batch of blood clotting factor IX, a number of hemophilia B patients in Germany recently became infected with human immunodeficiency virus type 1 (HIV-1). The nucleotide sequences of cloned HIV-1 envelope gene regions including the variable V3 loop and the V4 region derived from short-term virus cultures and directly from peripheral blood cells of these patients were shown to be highly homologous. Based on the assumption that the corresponding consensus sequence (termed HIV-1MBK) was identical to the genotype of the initially infecting virus, we were able to construct phylogenetic trees of the developing quasispecies in two patients studied in detail. True intermediates between input and multiply mutated genotypes were found in individual blood samples. Except for the initially infecting variant HIV-1MBK, variants found at 11 months postinfection had replaced those seen at 5 months postinfection. Variability early after infection was shown to cluster in two small regions located 3' of the V3 loop (i.e., outside the loop) and within the V4 region. This communication therefore describes the evolution of an HIV-1 quasispecies in humans starting from a single genotype. PMID- 1502147 TI - A pattern of accumulation of a somatic deletion of mitochondrial DNA in aging human tissues. AB - An assay that selectively amplifies a specific deletion of the mitochondrial genome has been used to study the extent of the deletion's accumulation in a variety of human tissues. The deletion occurs at much higher levels in nervous and muscle tissues than in all other tissues studied. The variation in deletion level between the same tissues in different persons of similar age appears to be less than the variation among tissues within an individual. Tests for artifactual explanations of the level differences were each negative. Three cellular parameters that are correlated with the level of the deletion are identified. The preferential accumulation of deleterious mitochondrial mutations in a restricted subset of aging human tissues may compound deficiencies of function in those tissues that accrue with age. PMID- 1502148 TI - Involvement of endogenous tumor necrosis factor alpha and transforming growth factor beta during induction of collagen type II arthritis in mice. AB - Both tumor necrosis factor alpha (TNF-alpha) and transforming growth factor beta (TGF-beta) are found in synovial fluid from arthritic joints of humans and of rodents with experimental arthritis. The role of endogenously produced TGF-beta and TNF in the pathogenesis of collagen type II-induced arthritis (CIA) in DBA/1 mice was examined by determining the effect of neutralizing monoclonal antibodies to these factors on the course of the disease. Endogenously produced as well as systemically administered TGF-beta 1 and TNF-alpha had opposite effects, since TGF-beta 1 and anti-TNF protected against CIA, whereas anti-TGF-beta and TNF alpha increased CIA incidence and/or severity. Intraperitoneally injected TGF beta 1 at a dose of 2 micrograms per day for 14 days significantly ameliorated arthritis, even when started at the time of arthritis development, although it did not reverse established disease. The resistance to CIA induction caused by a prior intravenous injection of collagen type II was not significantly influenced by the simultaneous injection of TGF-beta 1, TNF-alpha, or interleukin 1 alpha. It is concluded that the endogenous production of TNF and TGF-beta is important in determining the course of CIA. PMID- 1502149 TI - Apolipoprotein AI mutation Arg-60 causes autosomal dominant amyloidosis. AB - A mutation in the gene for apolipoprotein AI (apoAI) was identified in an English family with autosomal dominant non-neuropathic systemic amyloidosis. The plasma of all affected individuals contained a variant apoAI with one additional charge, as well as normal apoAI. The propositus was heterozygous; the coding region of his apoAI gene contained both the normal sequence and a single-base substitution changing the codon for residue 60 of the mature protein from CTG (leucine) to CGG (arginine). Allele-specific oligonucleotide hybridization showed that the other affected individuals were also heterozygotes and that there was concordance of the mutant allele with the presence of variant plasma apoAI. Amyloid fibrils isolated from the spleen of the propositus consisted of proteins that ran as a doublet with an apparent mass of approximately 10 kDa in SDS/PAGE and a trace band at 28 kDa. Electrospray mass spectrometry of the purified 10-kDa material revealed components with mass corresponding to the N-terminal 88, 92, 93, and 94 residues of apoAI each with substitution of arginine for leucine. These observations were confirmed by direct protein sequencing and laser desorption time-of-flight mass analysis. No material with the normal apoAI sequence was detected. The trace band at 28 kDa yielded the N-terminal sequence of mature apoAI, indicating that intact or minimally degraded apoAI was also present in the fibril preparation. Discovery of this mutation and the detailed characterization of the apoAI fragments that form the amyloid fibrils open additional avenues for investigation of amyloidogenesis. PMID- 1502150 TI - Somatotopic organization in rat striatum: evidence for a combinational map. AB - 2-Deoxy-D-[14C]glucose autoradiography was used in awake rats to map neural activity in the sensorimotor sector of striatum. Stimulation of hindlimb, trunk, or forelimb activated primary sensory cortex in a localized columnar pattern, indicating activation of somatosensory receptors and a discrete cortical functional unit. In sensorimotor striatum, an image analysis detection technique revealed regions of maximal activity, or features, that formed a patchy pattern of activation reminiscent of the known anatomic patterns of cortico-striate terminals. Ipsilateral as well as contralateral activation was observed. The activated areas revealed a body map in striatum that was organized in a manner consistent with cortical topography (dorsoventrally: hindlimb, trunk, forelimb) at most anteroposterior levels, similar to that found in other species. However, at other levels, a different organization (e.g., trunk, hindlimb, forelimb) was observed. Furthermore, the arrangements of body region and side were also unique at different anteroposterior levels. Thus, functional activity showed multiple, different juxtapositions of body elements--i.e., a combinational map. The data suggest that striatum may provide an anatomic substrate for different combinations of inputs necessary to select and integrate movement. PMID- 1502151 TI - Serine tRNA complementary to the nonuniversal serine codon CUG in Candida cylindracea: evolutionary implications. AB - In the asporogenic yeast Candida cylindracea, the codon CUG is read as serine instead of leucine. This is an unusual instance in which the amino acid assignment of a codon deviates from the universal code. To infer the evolutionary process of this change, the tRNA with the anticodon sequence CAG, which is complementary to and thus responsible for translation of the codon CUG, has been identified. Indeed, this tRNA translates an in-frame CUG codon in a synthetic mRNA as serine in an in vitro translation system. The gene for the tRNA is interrupted by an intron in the anticodon loop. Sequence comparisons of the tRNA and its gene suggest that a single cytidine was inserted into the anticodon loop of the gene for tRNA(Ser)IGA during evolution to produce tRNA(Ser)CAG. The tRNA(Ser)CAG may be produced from its precursor molecule containing the cytidine insertion by splicing. PMID- 1502152 TI - Purification of the heteromeric protein binding to the URS1 transcriptional repression site in Saccharomyces cerevisiae. AB - The protein that binds to the URS1 site situated upstream of many genes in Saccharomyces cerevisiae is a central element responsible for global negative control of transcription in this organism. Among the genes whose expression is regulated by this protein are those that participate in nitrogen metabolism, carbon metabolism, electron transport, inositol metabolism, heat shock response, meiosis, and sporulation. This factor, binding URS1 factor (BUF), has been purified and shown to be a heteromeric protein composed of 37.5- and 73.5-kDa monomers. The heteromeric form of BUF is stably maintained both in solution and bound to its DNA target site. PMID- 1502153 TI - Complexes of tissue-type plasminogen activator and its serpin inhibitor plasminogen-activator inhibitor type 1 are internalized by means of the low density lipoprotein receptor-related protein/alpha 2-macroglobulin receptor. AB - Tissue-type plasminogen activator and urokinase are serine proteases secreted by many cell types that participate in biological processes, such as tissue restructuring, cell migration, and tumor metastasis. Clinically, these proteases are used to dissolve coronary fibrin clots that are the proximal causes of acute myocardial infarction. In vivo, the activity of these enzymes is controlled by plasminogen-activator inhibitors, members of the serpin family of protease inhibitors. This study shows that tissue-type plasminogen activator-inhibitor complexes bind in solution to low density lipoprotein receptor-related protein (LRP), a large heterodimeric ubiquitous membrane receptor. In cultured cells, endocytosis and degradation of these complexes is reduced by polyclonal antibodies directed against LRP and inhibited by a M(r) 39,000 protein that binds to LRP and inhibits its interaction with previously known ligands, including apolipoprotein E and alpha 2-macroglobulin. We propose a role for LRP in the clearance of plasminogen activator-inhibitor complexes that is analogous to its function in the endocytosis of alpha 2-macroglobulin-protease complexes. PMID- 1502154 TI - Low density lipoprotein receptor-related protein/alpha 2-macroglobulin receptor is an hepatic receptor for tissue-type plasminogen activator. AB - Tissue-type plasminogen activator (t-PA), a serine protease that catalyzes the initial and rate-limiting step in the fibrinolytic cascade, is cleared rapidly in vivo by the liver. Using chemical crosslinking, we have recently identified a plasminogen-activator inhibitor type 1 (PAI-1)-independent t-PA clearance receptor on rat hepatoma MH1C1 cells with a relative molecular mass of approximately 500 kDa. Another recently identified membrane receptor, low density lipoprotein receptor-related protein/alpha 2-macroglobulin receptor (LRP/alpha 2MR), was also detected on MH1C1 hepatoma cells by using immunoprecipitation with anti-LRP/alpha 2MR antibody. When analyzed by SDS/PAGE, we found the t-PA receptor identified on MH1C1 cells comigrated with the large subunit of LRP/alpha 2MR. The t-PA receptor was immunoprecipitated by an anti-LRP/alpha 2MR antibody after chemical crosslinking of specifically bound 125I-labeled t-PA to its receptor. Through chemical crosslinking studies, we found that t-PA and methylamine-activated alpha 2-macroglobulin could bind to LRP/alpha 2MR simultaneously without competing with one another for binding, suggesting that the two ligands bound to two independent sites on the LRP/alpha 2MR molecule. Furthermore, a 39-kDa protein, which modulates ligand binding to LRP/alpha 2MR, was also found to inhibit t-PA binding to its receptor. These data thus show that the t-PA clearance receptor identified on MH1C1 hepatoma cells is LRP/alpha 2MR. PMID- 1502155 TI - Intracellular accumulation and resistance to degradation of the Alzheimer amyloid A4/beta protein. AB - The A4 or beta protein is a peptide that constitutes the major protein component of senile plaques in Alzheimer disease. The A4/beta protein is derived from a larger, transmembrane amyloid precursor protein (APP). The putative abnormal processing events leading to amyloid accumulation are largely unknown. Here we report that a 42-residue synthetic peptide, beta 1-42, corresponding to one of the longer forms of the A4/beta protein, accumulates in cultured human skin fibroblasts and is stable for at least 3 days. The peptide appears to accumulate intracellularly, since it does not accumulate under conditions that prevent endocytosis and accumulation is correlated with the acquisition of resistance to removal by trypsin digestion. This intracellular accumulation is also correlated with the ability of the peptide to aggregate as determined by SDS/polyacrylamide gel electrophoresis. At low concentrations of the beta 1-42 peptide, which favor the nonaggregated state, no accumulation is observed. Shorter peptide analogs (28 or 39 residues) that are truncated at the C terminus, which lack the ability to aggregate in SDS gels, fail to accumulate. The accumulated intracellular beta 1 42 peptide is in an aggregated state and is contained in a dense organellar compartment that overlaps the distribution of late endosomes or secondary lysosomes. Immunofluorescence of the internalized peptide in permeabilized cells reveals that it is contained in granular deposits, consistent with localization in late endosomes or secondary lysosomes. Sequence analysis indicates that some of the internalized peptide is subject to N-terminal trimming. These results suggest that the aggregated A4/beta protein may be resistant to degradation and suggest that the A4/beta protein may arise, at least in part, by endosomal or lysosomal processing of APP. Our results also suggest that relatively nonspecific proteolysis may be sufficient to generate the A4/beta protein if this part of APP is selectively resistant to proteolysis. PMID- 1502156 TI - The T-DNA-linked VirD2 protein contains two distinct functional nuclear localization signals. AB - Agrobacterium tumefaciens causes neoplastic growth in plants by transferring a piece of DNA, called T-DNA, into the nucleus of the plant cell. The virulence protein VirD2 of A. tumefaciens is tightly linked to the T-DNA and is thought to direct it to the plant genome. Here we show that the VirD2 protein contains two nuclear localization signals that are functional both in yeast and in plant cells. One signal is located in the N-terminal part of the protein and resembles a single-cluster-type nuclear localization signal. The second signal is near the C terminus and is a bipartite-type nuclear localization signal. The involvement of these sequences in the entry of the T-DNA into the nucleus is discussed. PMID- 1502157 TI - MAZ, a zinc finger protein, binds to c-MYC and C2 gene sequences regulating transcriptional initiation and termination. AB - ME1a1, a 16-base-pair nuclear factor binding site residing between the c-MYC P1 and P2 transcription initiation sites, is required for P2 activity. A cDNA encoding a 477-amino acid zinc finger protein designated MAZ (MYC-associated zinc finger protein) was cloned from a HeLa lambda gt11 library by screening with a concatamerized ME1a1 binding site probe. In addition to six potential zinc fingers of the Cys2His2 type, MAZ contains an amino-terminal proline-rich domain and several polyalanine tracts. Its mRNA was present in all human tissues tested except for kidney, as a doublet of approximately 2.5 and 2.7 kilobases, along with differentially expressed minor species. MAZ bound specifically to the wild type ME1a1 sequence but not to a ME1a1 mutant that also failed to yield P2 activity. When expressed as a fusion protein in a pMAL-c vector, MAZ binds with specificity to a GA box sequence (GGGAGGG) found in the c-MYC P2 promoter, to the P2 attenuator region within the gene's first exon, and to a related sequence involved in the transcriptional termination of the C2 gene. MAZ may encode a transcription factor with dual roles in transcription initiation and termination. PMID- 1502158 TI - Refolding and oriented insertion of a membrane protein into a lipid bilayer. AB - We have studied the refolding and membrane insertion of the outer membrane protein OmpA of Escherichia coli. The protein was extracted from its native membrane by sonication in the presence of urea and dissolved in the urea/water mixture in unfolded form. In this form it was purified. Upon addition of preformed lipid vesicles, the protein spontaneously refolded and inserted into the vesicle membranes. The vesicles had to be small and the lipids had to be in the fluid state. The insertion occurred in an oriented manner. PMID- 1502159 TI - Sensitivity of transformation to small differences in population density during serial passage of NIH 3T3 cells. AB - Early passages of the NIH 3T3 mouse cell line undergo spontaneous neoplastic transformation leading to the development of transformed foci if grown to confluence in 2% (vol/vol) calf serum (CS) and left there for more than a week. Transfer of the postconfluent cultures results in the appearance of large numbers of transformed foci; many of them are larger and denser than those in the original culture. If the cells are continually kept at low population densities by frequent passages in 10% CS, they lose the capacity to undergo spontaneous transformation. If however the low-density passages are made in 2% CS or in 10% (vol/vol) fetal bovine serum, both of which support lower growth rates and saturation densities than does 10% CS, they gain the capacities to grow to high saturation densities and produce more foci when grown to confluence in 2% CS. These increases are proportional to the population densities used in the frequent passages, although the densities are all kept well below confluence. We conclude that the combined constraints of submaximal serum plus those of the limited cell contacts of the low cell densities used here elicit an adaptive response that endows the entire population with increased growth capacity. The increased growth capacity of the heterogeneous population in turn increases the capacity of a fraction of the population to initiate distinctive transformed foci. Similar studies have indicated that the capacity of cells to produce tumors and metastases in mice and rats is enhanced by prior maintenance at high density in culture. We propose the concept of progressive state selection to account for the general increase in the growth capacity of cells that is elicited by moderate constraints on their growth and metabolism. PMID- 1502160 TI - Association of titin and myosin heavy chain in developing skeletal muscle. AB - To understand molecular interactions that organize developing myofibrils, we examined the biosynthesis and interaction of titin and myosin heavy chain in cultures of developing muscle. Use of pulse-labeling, immunoprecipitation, and a reversible cross-linking procedure demonstrates that within minutes of synthesis, titin and myosin heavy chain can be chemically cross-linked into very large, detergent-resistant complexes retaining many features of intact myotubes. These complexes, predominantly of titin and myosin, occur very early in myofibrillogenesis as well as later. These data suggest that synthesis and assembly of titin and myosin are temporally and spatially coordinated in nascent myofibrils and support the hypothesis that titin molecules help to organize sarcomere formation. PMID- 1502161 TI - The evolutionary selection of DNA base pairs in gene-regulatory binding sites. AB - The DNA base-pair sequences that serve as gene-regulatory sites have been selected during evolution to provide an appropriate functional binding for a particular protein. In most cases, the function depends on the binding probability, which can be influenced both by the binding strength and by the abundance of the protein in the cell. As a consequence, the same function can be achieved with strong binding sites and a small amount of protein as with weak binding sites and a large amount of protein. However, increasing the protein burden will decrease the growth rate of the cells, even when all functions remain the same. Thus, for maximal growth, the protein levels should be as low as possible and the binding correspondingly strong. On the other hand, sequences with a weaker binding can be formed in many more ways and are, therefore, more probable, and random mutations are more likely to produce them. Thus, the selection pressure against an increased protein burden can be balanced against the random mutational drift in the recognition sequences, thereby tying together the statistics of base-pair choice, the binding strength, and the protein burden. In terms of this model, the selection pressure can be estimated from the properties of a gene-regulatory protein and its recognition sites. A key feature is the mutational randomization pressure that appears as a fundamental force shaping the optimal solutions that provide maximal growth. The model is tested on a number of gene-regulatory systems in Escherichia coli. The same principles should hold for all proteins for which overall activity in the cell is proportional to abundance; then the selective pressure to increase the efficiency of an individual protein cannot be larger than the selective pressure to decrease the total protein burden. PMID- 1502162 TI - Pyrimidine dimers in DNA initiate systemic immunosuppression in UV-irradiated mice. AB - Exposing the skin of mice to UV radiation interferes with the induction of delayed and contact hypersensitivity immune responses initiated at nonirradiated sites. The identity of the molecular target in the skin for these immunosuppressive effects of UV radiation remains controversial. To test the hypothesis that DNA is the target for UV-induced systemic immunosuppression, we exposed C3H mice to UV radiation and then used liposomes to deliver a dimer specific excision repair enzyme into the epidermis in situ. The application of T4 endonuclease V encapsulated in liposomes to UV-irradiated mouse skin decreased the number of cyclobutane pyrimidine dimers in the epidermis and prevented suppression of both delayed and contact hypersensitivity responses. Moreover, the formation of suppressor lymphoid cells was inhibited. Control, heat-inactivated endonuclease encapsulated in liposomes had no effect. These studies demonstrate that DNA is the major target of UV radiation in the generation of systemic immunosuppression and suggest that the primary molecular event mediating these types of immunosuppression by UV radiation is the formation of pyrimidine dimers. Furthermore, they illustrate that the delivery of lesion-specific DNA repair enzymes to living skin after UV irradiation is an effective tool for restoring immune function and suggest that this approach may be broadly applicable to preventing other alterations caused by DNA damage. PMID- 1502164 TI - Classification and evolution of alpha-amylase genes in plants. AB - The DNA sequences for 17 plant genes for alpha-amylase (EC 3.2.1.1) were analyzed to determine their phylogenetic relationship. A phylogeny for these genes was obtained using two separate approaches, one based on molecular clock assumptions and the other based on a comparison of sequence polymorphisms (i.e., small and localized insertions) in the alpha-amylase genes. These polymorphisms are called "alpha-amylase signatures" because they are diagnostic of the gene subfamily to which a particular alpha-amylase gene belongs. Results indicate that the cereal alpha-amylase genes fall into two major classes: AmyA and AmyB. The AmyA class is subdivided into the Amy1 and Amy2 subfamilies previously used to classify alpha amylase genes in barley and wheat. The AmyB class includes the Amy3 subfamily to which most of the alpha-amylase genes of rice belong. Using polymerase chain reaction and oligonucleotide primers that flank one of the two signature regions, we show that the AmyA and AmyB gene classes are present in approximately equal amounts in all grass species examined except barley. The AmyB (Amy3 subfamily) genes in the latter case are comparatively underrepresented. Additional evidence suggests that the AmyA genes appeared recently and may be confined to the grass family. PMID- 1502163 TI - Mammalian skeletal muscle fibers distinguished by contents of phosphocreatine, ATP, and Pi. AB - We tested the proposition that muscle cell types have different contents of phosphocreatine (PCr), ATP, and Pi by 31P NMR spectroscopy and HPLC analyses of adult rat and mouse muscles containing various volume fractions of different fiber types. There was a 2-fold difference in the PCr content between muscles with a high volume fraction of fiber types 1 and 2x versus those with fast-twitch (types 2a and 2b) fiber types. Pi content was low, and PCr and ATP contents were high in muscles with large contents of type 2b and 2a fibers; the reverse was true in muscles with a large volume fraction of type 1 and 2x fibers. There is a large range in the Pi/PCr ratios in normal resting muscles, from less than 0.05 in type 2 to 0.51 in type 1 fibers, depending upon the distribution of their component fiber types. In all muscles, the peak area resulting from the beta phosphate of ATP constituted approximately 13% of the sum of all peak areas observable in the 31P spectrum. Fiber types 2a and 2b were not distinguishable, and the content of type 2x fibers was similar to type 1 fibers. From the profile of these metabolites, we could distinguish only two classes of fibers. For type 2a and 2b fibers, the intracellular concentrations were 8 mM ATP, 39 mM total creatine, 32 mM PCr, 0.8 mM Pi, and 8 microM ADP. For type 1 and 2x fibers, these quantities were 5 mM ATP, 23 mM total creatine, 16 mM PCr, 6 mM Pi, and 11 microM ADP. Thus our results establish an additional criterion upon which to distinguish skeletal muscle cells, one based on the resting content of bioenergetically important metabolites. These results also provide the basis for estimating skeletal muscle fiber-type composition from noninvasive NMR spectroscopic data. PMID- 1502165 TI - Reciprocal control of RNA-binding and aconitase activity in the regulation of the iron-responsive element binding protein: role of the iron-sulfur cluster. AB - Several mechanisms of posttranscriptional gene regulation are involved in regulation of the expression of essential proteins of iron metabolism. Coordinate regulation of ferritin and transferrin receptor expression is produced by binding of a cytosolic protein, the iron-responsive element binding protein (IRE-BP) to specific stem-loop structures present in target RNAs. The affinity of this protein for its cognate RNA is regulated by the cell in response to changes in iron availability. The IRE-BP demonstrates a striking level of amino acid sequence identity to the iron-sulfur (Fe-S) protein mitochondrial aconitase. Moreover, the recombinant IRE-BP has aconitase function. The lability of the Fe-S cluster in mitochondrial aconitase has led us to propose that the mechanism by which iron levels are sensed by the IRE-BP involves changes in an Fe-S cluster in the IRE-BP. In this study, we demonstrate that procedures aimed at altering the IRE-BP Fe-S cluster in vitro reciprocally alter the RNA binding and aconitase activity of the IRE-BP. The changes in the RNA binding of the protein produced in vitro appear to match the previously described alterations of the protein in response to iron availability in the cell. Furthermore, iron manipulation of cells correlates with the activation or inactivation of the IRE-BP aconitase activity. The results are consistent with a model for the posttranslational regulation of the IRE-BP in which the Fe-S cluster is altered in response to the availability of intracellular iron and this, in turn, regulates the RNA-binding activity. PMID- 1502167 TI - Polarized distribution of glucose transporter isoforms in Caco-2 cells. AB - We have examined the expression and cellular location of facilitated glucose transporter proteins (GLUT1, -3, and -5) in a human colonic epithelial cell line (Caco-2) by using peptide-specific antibodies. A differential cellular distribution of these transporters was observed in differentiated (greater than 14 days postconfluence) Caco-2 cells by immunofluorescence and immunoelectron microscopy. GLUT1 was localized primarily to the basolateral membrane, whereas GLUT3 was predominantly localized to the apical membrane. GLUT5, which was detected in only approximately 40% of fully differentiated Caco-2 cells, was found primarily in the apical membrane but was also present in both basolateral and intracellular membranes. A Na(+)-independent glucose transport system in the apical membrane of Caco-2 cells has been described previously [Blais, A., Bissonnette, A. & Berteloot, A. (1987) J. Membr. Biol. 99, 113-125], and we propose that GLUT3 mediates this process. The amino acid sequence identity (57%) and structural conservation between GLUT1 and GLUT3 may make these transporters an ideal model system for examining the molecular basis for polarized sorting of membrane proteins. PMID- 1502166 TI - Identification of a peroxisome proliferator-responsive element upstream of the gene encoding rat peroxisomal enoyl-CoA hydratase/3-hydroxyacyl-CoA dehydrogenase. AB - Ciprofibrate, a hypolipidemic drug that acts as a peroxisome proliferator, induces the transcription of genes encoding peroxisomal beta-oxidation enzymes. To identify cis-acting promoter elements involved in this induction, 5.8 kilobase pairs of promoter sequence from the gene encoding rat peroxisomal enoyl-CoA hydratase/3-hydroxyacyl-CoA dehydrogenase (EC 4.2.1.17/EC 1.1.1.35) was inserted upstream of a luciferase reporter gene. Transfection of this expression vector into rat hepatoma H4IIEC3 cells in the presence of ciprofibrate resulted in a 5- to 10-fold, cell type-specific increase in luciferase activity as compared to cells transfected in the absence of drug. A peroxisome proliferator-responsive element (PPRE) was localized to a 196-nucleotide region centered at position 2943 from the transcription start site. This PPRE conferred ciprofibrate responsiveness on a heterologous promoter and functioned independently of orientation or position. Gel retardation analysis with nuclear extracts demonstrated that ciprofibrate-treated or untreated H4IIEC3 cells, but not HeLa cells or monkey kidney cells, contained sequence-specific DNA binding factors that interact with the PPRE. These results have implications for understanding the mechanisms of coordinated transcriptional induction of genes encoding peroxisomal proteins by hypolipidemic agents and other peroxisome proliferators. PMID- 1502168 TI - Disruption of the CD4-p56lck complex is required for rapid internalization of CD4. AB - CD4 is a cell surface glycoprotein expressed by a subset of T lymphocytes and functions to enhance T-cell activation. CD4 is noncovalently associated via the cytoplasmic domain with the protein-tyrosine kinase p56lck, a member of the src protein-tyrosine kinase family. Upon activation of protein kinase C by phorbol ester, CD4 is phosphorylated on cytoplasmic serine residues and internalized from the cell surface, and disruption of the CD4-p56lck complex occurs. The exact relationship between these events is likely to be functionally significant, as cytoplasmic-domain serine phosphorylation and internalization have been shown to regulate the function of receptors that possess intrinsic protein-tyrosine kinase activity. Here we demonstrate that p56lck slows the rate of phorbol 12-myristate 13-acetate-induced internalization of CD4 in a manner that depends on a physical association between p56lck and CD4. This decreased rate is due at least in part to a requirement for disruption of the CD4-p56lck complex prior to internalization of CD4. Furthermore, disruption of the CD4-p56lck complex appears to depend on the integrity of the cytoplasmic-domain serine at position 408, probably due to a requirement for phosphorylation. PMID- 1502169 TI - Purification and characterization of the diphtheria toxin repressor. AB - The diphtheria toxin repressor gene (dtxR) encodes a protein (DtxR) that regulates transcription of the diphtheria toxin gene (tox) by an iron-dependent mechanism. Cloned dtxR was expressed in Escherichia coli from the phage T7 gene 10 promoter, and DtxR was purified. Specific binding of DtxR to the tox+ operator was dependent on reduction of DtxR and the presence of ferrous ions. DtxR protected a sequence of approximately 30 nucleotide pairs, partially overlapping the tox promoter and containing a region of dyad symmetry, from digestion by DNase I. DtxR exhibited very little binding to the mutant tox-201 operator region and failed to bind to the promoter/operator region of the ferric uptake regulation (fur) gene of E. coli. PMID- 1502170 TI - Torsional stress generated by RecA protein during DNA strand exchange separates strands of a heterologous insert. AB - Previous studies have shown that the helical RecA nucleoprotein filament formed on a circular single strand of DNA causes the progressive, directional transfer of a complementary strand from naked linear duplex DNA to the nucleoprotein filament, even when the duplex contains a sizable heterologous insertion. Since RecA protein lacks demonstrable helicase activity, the mechanism by which it pushes strand exchange through long heterologous inserts has been a quandary. In the present study, a linear duplex substrate with an insertion of 110 base pairs in its middle yielded the expected products, whereas much less of the heteroduplex product was seen when the insertion was located at either end of the duplex substrate or 160 base pairs from the far end of the duplex substrate. In an ongoing reaction of the substrate with an insertion in its middle, P1 nuclease cleaved intermediates from the point of the insertion to various distal sites. Acting on a duplex substrate that contained a single nick located in the complementary strand just beyond the insertion, RecA protein formed joint molecules but failed to complete strand exchange. These data show that negative torsional stress is generated by distant homologous interactions that occur beyond the heterologous insertion and that such stress is essential for unwinding a heterologous insertion that otherwise halts strand exchange. PMID- 1502171 TI - In vivo footprint analysis of the HLA-DRA gene promoter: cell-specific interaction at the octamer site and up-regulation of X box binding by interferon gamma. AB - Analysis of the major histocompatibility complex class II gene promoter DRA has previously identified at least five cis-acting regions required for maximal expression. We have examined the DRA promoter for protein-DNA interactions in the intact cell, which may mediate transcriptional activation. Using in vivo genomic footprinting we identified interactions in B-cell lines at the octamer site and the Y, X1, and X2 boxes. Class II antigen expressing T-cell lines maintained contacts identical to B-cell lines, while class II-negative T-cell lines exhibited no interactions. In lymphoid cell lines, the octamer site is occupied and required for maximal expression. This is most likely due to the presence of the lymphoid-specific OTF-2 factor. In contrast, the class II-positive nonlymphoid glioblastoma cell line does not exhibit interactions at the octamer site despite the presence of the ubiquitous OTF-1 factor and an open binding site. Thus, the DRA promoter discriminates against OTF-1 activation at the level of DNA binding in the glioblastoma line. Interferon gamma induces class II expression in this glioblastoma cell line and, in parallel, up-regulates X1 and X2 box protein-DNA interactions, while all other interactions remain unchanged. These results suggest that interferon gamma functions on a poised promoter by altering weak, nonproductive interactions at the X boxes to strong interactions. These findings provide direct in vivo evidence to strongly suggest that the modulation of X1 and X2 interactions is an important constituent of the interferon gamma induction pathway. PMID- 1502172 TI - Sequencing heavy- and light-chain variable genes of single B-hybridoma cells by total enzymatic amplification. AB - We have devised a protocol to obtain accurate and complete sequences of the immunoglobulin heavy- and light-chain variable-region (VH and VL) genes of single B-hybridoma cells that express defined V genes. The amplification achieved ranges from 2 x 10(13)- to 1 x 10(14)-fold. Only one potential Taq DNA polymerase error was observed in 7590 nucleotides of sequence, thus permitting the identification of naturally occurring somatic mutations. The two-step nature of the amplification protocol provides sufficient DNA for a minimum of 160 sets of sequencing reactions of both the VH and VL genes from one cell without cloning. The amplification of relatively long segments of DNA in the first step of the protocol permits second-step amplification and sequencing of regions that flank VH and VL codons. Fractionating cellular lysates prior to the first step of amplification permits the separate amplification of V genes on opposite sister chromatids and possibly on opposite strands of the same DNA duplex. Accurate sequencing of VH and VL genes of defined germ-line origin that are expressed by single B cells taken directly from the animal is thus made feasible by this approach. PMID- 1502173 TI - Stochastic rearrangement of immunoglobulin variable-region genes in chicken B cell development. AB - The molecular mechanism by which immunoglobulin (Ig) gene rearrangement occurs is highly conserved between mammalian and avian species. However, in avian species, an equivalent to the mammalian pre-B cell, which has undergone Ig heavy-chain gene rearrangement and expresses mu heavy chains in the absence of Ig light-chain rearrangement, has not been convincingly demonstrated. It is consequently unclear whether an ordered progression of gene rearrangement events leading to functional Ig expression occurs in avian species. To examine the sequence of Ig gene rearrangement events in chicken B-cell development, we transformed day 12 embryo bursal cells with the REV-T(CSV) retrovirus. More than 100 clones were analyzed by Southern blotting and polymerase chain reaction for the presence of Ig gene rearrangements. The majority of these clones contained only germline Ig sequences. Several clones contained complete heavy- and light-chain rearrangements and 13 clones contained only heavy-chain rearrangements analogous to stages of mammalian B-cell development. However, 5 clones contained rearrangements of light-chain genes in the absence of complete heavy-chain rearrangement. Consequently, we conclude that rearrangement of chicken Ig light chain genes does not require heavy-chain variable-region rearrangement. This observation suggests that chicken Ig gene rearrangement events required for Ig expression occur stochastically rather than sequentially. PMID- 1502174 TI - Neurally evoked calcium transients in terminal Schwann cells at the neuromuscular junction. AB - We examined the effects of motor-nerve stimulation on the intracellular Ca2+ levels of Schwann cells, the glial cells at the frog neuromuscular junction. Schwann cells, which were loaded with the fluorescent Ca2+ indicator fluo-3 and examined by confocal microscopy, showed a transient increase in free Ca2+ within a few seconds of the onset of tetanic stimulation of the motor nerve. The Ca2+ response was specific to the synapse in that it was found in the terminal Schwann cells at the junction but not in the myelinating Schwann cells along the axon. The Ca2+ transients occurred in the presence of d-tubocurare, indicating that they were not mediated by nicotinic acetylcholine receptors and recurred when the stimulus was repeated. The Ca2+ response persisted after degeneration of the postsynaptic muscle fiber, demonstrating that the terminal Schwann cell was stimulated directly by presynaptic activity. The finding that terminal Schwann cells at the neuromuscular junction respond to presynaptic activity suggests that glial-cell function is modulated by synaptic transmission. PMID- 1502175 TI - Long-term expression of human adenosine deaminase in rhesus monkeys transplanted with retrovirus-infected bone-marrow cells. AB - Gene transfer into hemopoietic stem cells could offer a lasting cure for a variety of congenital disorders. As a preclinical test for such a gene therapy, rhesus monkeys were transplanted with autologous bone-marrow cells infected with helper-free recombinant retroviruses carrying the human adenosine deaminase gene. The in vivo regenerative capacity of the infected bone marrow could be conserved, suggesting survival of repopulating hemopoietic stem cells. In the hemopoietic system of transplanted animals the foreign gene could be observed for as long as the animals were analyzed (in two monkeys greater than 1 yr after transplantation). Genetically modified cell types and tissues included peripheral blood mononuclear cells, granulocytes, bone-marrow cells of various densities, and spleen and lymph nodes. The presence of the provirus in the short-living granulocytes greater than 1 yr after bone-marrow transplantation provided evidence for the transduction of very primitive hemopoietic progenitors. Moreover, the gene transfer resulted in sustained production of functional human adenosine deaminase enzyme in peripheral blood mononuclear cells. These results demonstrate the feasibility of bone-marrow gene-therapy approaches, in particular for treating adenosine deaminase deficiency. PMID- 1502176 TI - The particle SSV1 from the extremely thermophilic archaeon Sulfolobus is a virus: demonstration of infectivity and of transfection with viral DNA. AB - The lemon-shaped "virus-like" particle SSV1 produced by the thermophilic archaeon Sulfolobus shibatae has not previously been observed to infect any host. Using a plaque assay suitable for the extreme growth conditions of this archaeon, we have shown infection of Sulfolobus solfataricus by SSV1. Upon infection, the viral genome was always found integrated into a tRNA gene of the host chromosome, a situation similar to that in S. shibatae, proving that site-specific integration is involved in establishing the lysogenic state. As in S. shibatae, UV irradiation of lysogenized S. solfataricus led to virus production apparently not accompanied by cell lysis. We have also demonstrated the efficient uptake of exogenous DNA and its expression in Sulfolobus by transfecting S. solfataricus with SSV1 DNA by electroporation. Transfection efficiencies of up to 10(6) transfectants per microgram of DNA were obtained. PMID- 1502177 TI - Circulating estrogens in a male songbird originate in the brain. AB - Gonadal steroids act on brain to regulate the development and expression of vertebrate reproductive behavior. In addition, steroid targets in brain are an integral part of the feedback regulation of gonadal steroidogenesis. The actions of androgens in brain are often mediated by enzymatic activation or inactivation of circulating hormone, including local conversion of androgen to estrogen. We now report that in zebra finches, the brain synthesizes large quantities of estrogen from androgen and releases this estrogen into blood. Since there appears to be no other significant source of estrogen synthesis in adult male zebra finches, it is likely that the brain directly controls plasma levels of this steroid by contributing most or all of the high levels of estrogen found in the circulation. PMID- 1502178 TI - The antibiotic azatyrosine suppresses progesterone or [Val12]p21 Ha-ras/insulin like growth factor I-induced germinal vesicle breakdown and tyrosine phosphorylation of Xenopus mitogen-activated protein kinase in oocytes. AB - The antibiotic azatyrosine [DL-3-(5-hydroxy-2-pyridyl)alanine] suppressed meiotic maturation in oocytes induced by progesterone or the combination of [Val12]p21Ha ras microinjection and insulin-like growth factor I. The suppression was dose dependent in the range of 20-250 microM azatyrosine. In addition, azatyrosine blocked the tyrosine phosphorylation of Xp42, a member of the mitogen-activated protein kinase family, after progesterone or [Val12]p21Ha-ras/insulin-like growth factor I stimulation. Activation of maturation-promoting factor, as shown by a decrease in the tyrosine phosphorylation of the Xenopus homolog of p34cdc2, was also suppressed by azatyrosine. Azatyrosine had no effect in vivo or in vitro on the growth factor-induced autophosphorylation of the oocyte insulin-like growth factor I receptor. Azatyrosine has been shown by others [Shindo-Okada, N., Makabe, O., Nagahara, H. & Nishimura, S. (1989) Mol. Carcinog. 2, 159-167] to inhibit the growth of ras-transformed cells without affecting that of nontransformed cells. In oocytes, the antibiotic exerts an inhibitory action on both a ras-dependent and a ras-independent pathway. Lack of an effect of azatyrosine on germinal vesicle breakdown induced by the microinjection of an extract from mature oocytes, however, suggests that azatryosine is acting upstream of maturation-promoting factor activation. PMID- 1502179 TI - Simple derivation of TFIID-dependent RNA polymerase II transcription systems from Schizosaccharomyces pombe and other organisms, and factors required for transcriptional activation. AB - Resolution of whole cell extract through two chromatographic steps yields a single protein fraction requiring only the addition of TFIID for the initiation of transcription at RNA polymerase II promoters. This approach allows the convenient generation of RNA polymerase II transcription systems from Saccharomyces cerevisiae, human lymphocytes, and Schizosaccharomyces pombe. TFIIDs from all three organisms are interchangeable among all three systems. The S. cerevisiae and Sch. pombe systems support effects of acidic activator proteins, provided a further protein fraction from S. cerevisiae is supplied. This further fraction is distinct from the mediator of transcriptional activation described previously and represents a second component in addition to general initiation factors that may facilitate a response to acidic activators. PMID- 1502180 TI - ATP hydrolysis by initiation factor 4A is required for translation initiation in Saccharomyces cerevisiae. AB - Saccharomyces cerevisiae translation initiation factor eIF-4A, an RNA helicase of the Asp-Glu-Ala-Asp (DEAD) box protein family, was mutated in the putative ATP binding site and expressed in Escherichia coli. Mutant proteins with alanine at position 66 replaced by glycine [eIF-4A(A66G)] or valine [eIF-4A(A66V)] were purified from Escherichia coli extracts and analyzed in vitro for activity in ATP crosslinking, ATP hydrolysis, RNA helicase, and translation assays. The results show that in vitro ATP hydrolysis activity, RNA helicase activity, and translation activity of eIF-4A correlate with in vivo activity of the factor. Whereas eIF-4A(A66G) showed wild-type activity in all assays, eIF-4A(A66V) was active in ATP crosslinking but inactive in ATP hydrolysis and RNA helicase assays. In vitro translation was supported by wild-type eIF-4A and eIF-4A(A66G) but not by eIF-4A(A66V). The results show that, for their translation, the majority of mRNAs from Saccharomyces cerevisiae including an mRNA with the initiator AUG positioned 8 nucleotides downstream of the cap structure require eIF-4A that is able to hydrolyze ATP. PMID- 1502181 TI - Origins of the Indo-Europeans: genetic evidence. AB - Two theories of the origins of the Indo-Europeans currently compete. M. Gimbutas believes that early Indo-Europeans entered southeastern Europe from the Pontic Steppes starting ca. 4500 B.C. and spread from there. C. Renfrew equates early Indo-Europeans with early farmers who entered southeastern Europe from Asia Minor ca. 7000 BC and spread through the continent. We tested genetic distance matrices for each of 25 systems in numerous Indo-European-speaking samples from Europe. To match each of these matrices, we created other distance matrices representing geography, language, time since origin of agriculture, Gimbutas' model, and Renfrew's model. The correlation between genetics and language is significant. Geography, when held constant, produces a markedly lower, yet still highly significant partial correlation between genetics and language, showing that more remains to be explained. However, none of the remaining three distances--time since origin of agriculture, Gimbutas' model, or Renfrew's model--reduces the partial correlation further. Thus, neither of the two theories appears able to explain the origin of the Indo-Europeans as gauged by the genetics-language correlation. PMID- 1502182 TI - Nitric oxide circulates in mammalian plasma primarily as an S-nitroso adduct of serum albumin. AB - We have recently shown that nitric oxide or authentic endothelium-derived relaxing factor generated in a biologic system reacts in the presence of specific protein thiols to form S-nitrosoprotein derivatives that have endothelium-derived relaxing factor-like properties. The single free cysteine of serum albumin, Cys 34, is particularly reactive toward nitrogen oxides (most likely nitrosonium ion) under physiologic conditions, primarily because of its anomalously low pK; given its abundance in plasma, where it accounts for approximately 0.5 mM thiol, we hypothesized that this plasma protein serves as a reservoir for nitric oxide produced by the endothelial cell. To test this hypothesis, we developed a methodology, which involves UV photolytic cleavage of the S--NO bond before reaction with ozone for chemiluminescence detection, with which to measure free nitric oxide, S-nitrosothiols, and S-nitrosoproteins in biologic systems. We found that human plasma contains approximately 7 microM S-nitrosothiols, of which 96% are S-nitrosoproteins, 82% of which is accounted for by S-nitroso-serum albumin. By contrast, plasma levels of free nitric oxide are only in the 3-nM range. In rabbits, plasma S-nitrosothiols are present at approximately 1 microM; 60 min after administration of NG-monomethyl-L-arginine at 50 mg/ml, a selective and potent inhibitor of nitric oxide synthetases, S-nitrosothiols decreased by approximately 40% (greater than 95% of which were accounted for by S nitrosoproteins, and approximately 80% of which was S-nitroso-serum albumin); this decrease was accompanied by a concomitant increase in mean arterial blood pressure of 22%. These data suggest that naturally produced nitric oxide circulates in plasma primarily complexed in S-nitrosothiol species, principal among which is S-nitroso-serum albumin. This abundant, relatively long-lived adduct likely serves as a reservoir with which plasma levels of highly reactive, short-lived free nitric oxide can be regulated for the maintenance of vascular tone. PMID- 1502183 TI - Derivation of a biologically contained replication system for human immunodeficiency virus type 1. AB - Human immunodeficiency virus type 1 (HIV-1) proviral mutants that lack viral regulatory genes are unable to replicate unless rescued by complementation in trans. Structurally intact virus can be produced by infecting recombinant cell lines expressing the deficient genes. A HIV-1 mutant functionally defective in tat and rev (vIIIB delta Tat/Rev), which replicates only in a recombinant T-cell line expressing tat and rev (CEMTART), is described in this report. Infection of the CEMTART cell line with vIIIB delta Tat/Rev permits the complete HIV-1 life cycle, including cytopathology, decreased expression of CD4, and production of viral structural proteins, to be biologically contained. Culture supernatants from infected CEMTART contain virus that is able to replicate only in uninfected CEMTART. No reversion of vIIIB delta Tat/Rev to wild-type HIV-1 was observed as measured either by sequencing proviral vIIIB delta Tat/Rev or by detecting the ability of vIIIB delta Tat/Rev to replicate in CEM or activated CD4-bearing T lymphocytes. Defective HIV-1 mutants produced by trans complementation of essential genes permit infection and analysis of defined genotypes on cellular function and phenotype. Authentic HIV-1 structural proteins and infected cells can be prepared in mass, and agents that interfere with the HIV-1 life cycle can be studied on a large scale with minimum risk of exposing workers to virulent HIV 1. PMID- 1502184 TI - Magnetite biomineralization in the human brain. AB - Although the mineral magnetite (Fe3O4) is precipitated biochemically by bacteria, protists, and a variety of animals, it has not been documented previously in human tissue. Using an ultrasensitive superconducting magnetometer in a clean-lab environment, we have detected the presence of ferromagnetic material in a variety of tissues from the human brain. Magnetic particle extracts from solubilized brain tissues examined with high-resolution transmission electron microscopy, electron diffraction, and elemental analyses identify minerals in the magnetite maghemite family, with many of the crystal morphologies and structures resembling strongly those precipitated by magnetotactic bacteria and fish. These magnetic and high-resolution transmission electron microscopy measurements imply the presence of a minimum of 5 million single-domain crystals per gram for most tissues in the brain and greater than 100 million crystals per gram for pia and dura. Magnetic property data indicate the crystals are in clumps of between 50 and 100 particles. Biogenic magnetite in the human brain may account for high field saturation effects observed in the T1 and T2 values of magnetic resonance imaging and, perhaps, for a variety of biological effects of low-frequency magnetic fields. PMID- 1502185 TI - Identification of ubiquitous high-molecular-mass, heat-stable microtubule associated proteins (MAPs) that are related to the Drosophila 205-kDa MAP but are not related to the mammalian MAP-4. AB - AX3, a monoclonal antibody raised against isolated microtubule-organizing centers of Dictyostelium discoideum, stains microtubule-containing structures in species ranging from Dictyostelium to human. On immunoblots, the AX3 antibody recognizes heat-stable proteins in the 260- to 280-kDa molecular-mass range in a number of different species. The AX3 antigens from HeLa and embryonic mouse fibroblast cells coprecipitate with microtubules in vitro, indicating that these antigens are, indeed, MAPs. The AX3 antigens are not immunologically related to the mammalian MAP-2 or MAP-4 but are related to the 205-kDa MAP of Drosophila. This report describes a structural-type MAP in Dictyostelium and a MAP that is detected in a wide variety of species. The Drosophila 205-kDa MAP had previously been proposed to represent a member of the MAP-4 class of proteins. From the results reported here, however, it is suggested that proteins recognized by AX3 monoclonal antibody, including the Drosophila 205-kDa MAP, represent a distinct class of MAPs that has been widely conserved through evolution. PMID- 1502186 TI - Human glucokinase gene: isolation, characterization, and identification of two missense mutations linked to early-onset non-insulin-dependent (type 2) diabetes mellitus. AB - DNA polymorphisms in the glucokinase gene have recently been shown to be tightly linked to early-onset non-insulin-dependent diabetes mellitus in approximately 80% of French families with this form of diabetes. We previously identified a nonsense mutation in exon 7 in one of these families and showed that it was the likely cause of glucose intolerance in this dominantly inherited disorder. Here we report the isolation and partial sequence of the human glucokinase gene and the identification of two missense mutations in exon 7, Thr-228----Met and Gly 261----Arg, that cosegregate with early-onset non-insulin-dependent diabetes mellitus. To assess the molecular mechanism by which mutations at these two sites may affect glucokinase activity, the crystal structure of the related yeast hexokinase B was used as a simple model for human beta-cell glucokinase. Computer assisted modeling suggests that mutation of Thr-228 affects affinity for ATP and mutation of Gly-261 may alter glucose binding. The identification of mutations in glucokinase, a protein that plays an important role in hepatic and beta-cell glucose metabolism, indicates that early-onset non-insulin-dependent diabetes mellitus may be primarily a disorder of carbohydrate metabolism. PMID- 1502187 TI - Induction of endonuclease-mediated apoptosis in tumor cells by C-nitroso substituted ligands of poly(ADP-ribose) polymerase. AB - 6-Nitroso-1,2-benzopyrone and 3-nitrosobenzamide, two C-nitroso compounds that inactivate the eukaryotic nuclear protein poly(ADP-ribose) polymerase [NAD+:poly(adenosine diphosphate D-ribose) ADP-D-ribosyltransferase, ADPRT, EC 2.4.2.30] at one zinc-finger site, completely suppressed the proliferation of leukemic and other malignant human cells and subsequently produced cell death. Tumoricidal concentrations of the drugs were relatively harmless to normal bone marrow progenitor cells and to superoxide formation by neutrophil granulocytes. The cellular mechanism elicited by the C-nitroso compounds consists of apoptosis due to DNA degradation by the nuclear calcium/magnesium-dependent endonuclease. This endonuclease is maintained in a latent form by poly(ADP-ribosyl)ation, but inactivation of ADPRT by C-nitroso drugs derepresses the DNA-degrading activity. ADPRT is thus identified as a critical regulatory enzyme component of a DNA binding multiprotein system that plays a central function in defining DNA structures in the intact cell. PMID- 1502188 TI - Selective expression of interleukin 10, interferon gamma, and granulocyte macrophage colony-stimulating factor in ovarian cancer biopsies. AB - The variable clinical response seen with most cancer immunotherapy suggests that there is a large interindividual variation in immunologic response to tumors. One of the key functional parameters of an immune response is the local production of cytokines. As a method to survey the immune status of tumor-infiltrating cells, we have investigated the constitutive expression of cytokine mRNA in biopsies from epithelial ovarian carcinomas by using a PCR-assisted mRNA amplification assay. Using a set of cytokine-specific primers for 10 different cytokines, we have found selective expression of interleukin 10 (IL-10), granulocyte-macrophage colony-stimulating factor, and interferon gamma mRNA in ovarian tumor tissue as compared to normal ovaries and ovarian tumor cell lines. Such differences could not be explained by the extent of T-cell infiltration, since comparing samples with the same intensity of T-cell receptor (TCR) constant region alpha-chain product from the tumor and normal biopsies demonstrated different cytokine patterns. No IL-2 gene expression was detected in the tumor biopsies. IL-2 mRNA, however, became expressed after stimulation of the tumor-derived cells via the CD3 molecule but not after growth in recombinant IL-2 alone. Using the same methodology, we also analyzed the TCR variable region beta-chain gene repertoire. No restriction or biased expression of these genes was observed. PMID- 1502189 TI - Prolactin synthesized and secreted by human peripheral blood mononuclear cells: an autocrine growth factor for lymphoproliferation. AB - Prolactin has been shown to have an immunoregulatory role in the rodent immune response. A prolactin-like molecule has also been found in mouse splenocytes and a human B-lymphoblastoid cell line. We have evaluated whether human peripheral blood mononuclear cells (PBMCs) synthesize and/or secrete prolactin. We used the polymerase chain reaction (PCR) to generate a 276-base-pair prolactin product from human PBMCs, and Southern blot analysis confirmed that it was related to prolactin. Western blotting using a polyclonal antibody to prolactin indicated that cell extracts prepared from human PBMCs contained a high molecular mass (60 kDa) immunoreactive prolactin. To determine whether this PBMC prolactin was being secreted, we developed a highly sensitive and specific hormonal enzyme-linked immunoplaque assay. With this assay, we were able to detect human prolactin secretion from concanavalin A (Con A)- or phytohemagglutinin-stimulated PBMCs but not from unstimulated PBMCs. We next sought to determine whether this secreted prolactin could function as an autocrine growth factor in lymphoproliferation. We observed that anti-human prolactin antiserum significantly inhibited human PBMC proliferation in response to Con A or phytohemagglutinin. We conclude that a prolactin-like molecule is synthesized and secreted by human PBMCs and that it functions in an autocrine manner as a growth factor for lymphoproliferation. PMID- 1502190 TI - Chloroplast DNA inversions and the origin of the grass family (Poaceae). AB - The phylogenetic affinities of the grass family (Poaceae) have long been debated. The chloroplast genomes of at least some grasses have been known to possess three inversions relative to the typical gene arrangement found in most flowering plants. We have surveyed for the presence of these inversions in grasses and other monocots by polymerase chain reaction amplification with primers constructed from sequences flanking the inversion end points. Amplification phenotypes diagnostic for the largest inversion (28 kilobase pairs) were found in genera representing all grass subfamilies, and in the nongrass families Restionaceae, Ecdeiocoleaceae, and Joinvilleaceae, but not in any other monocots- notably, Flagellariaceae, Anarthriaceae, Cyperaceae, or Juncaceae. This finding is consistent with one of the two principal views of grass phylogeny in suggesting that Poaceae and Cyperaceae (sedges) are not closest relatives. A second (approximately 6 kilobases) inversion appears to occur in a subset of the families possessing the 28-kilobase inversion and links Joinvilleaceae and Poaceae, while the smallest inversion appears unique to grasses. These inversions thus provide a nested set of phylogenetic characters, indicating a hierarchy of relationships in the grasses and allies, with Joinvilleaceae identified as the likely sister group to the Poaceae. PMID- 1502191 TI - T-cell antigen receptor binding sites for the microbial superantigen staphylococcal enterotoxin A. AB - We have examined the interaction of the microbial superantigen staphylococcal enterotoxin A (SEA) with peptides corresponding to overlapping regions of the T cell antigen receptor beta chain variable region V beta 3. SEA is known to stimulate murine T cells bearing certain V beta elements, among them V beta 3. Five peptides were synthesized representing amino acids 1-24, 20-44, 39-60, 57 77, and 74-95 of V beta 3. We demonstrate here that soluble V beta 3-bearing beta chains can bind to a complex of SEA and major histocompatibility complex class II and that the synthetic peptide V beta 3-(57-77) blocked this interaction. The peptide V beta 3-(57-77) also inhibited SEA-induced interferon-gamma production and SEA-induced proliferation of B10.BR spleen cells. Conversely, the peptide corresponding to amino acids 57-77 of V beta 8.2, a V beta element that is not recognized by SEA, decreased staphylococcal enterotoxin C-2-induced proliferation but did not affect SEA-induced proliferation. The peptide inhibition of SEA induced function was due at least in part to inhibition of V beta 3-bearing T cell activity, since the percentage of T cells reactive with an anti-V beta 3 monoclonal antibody was significantly reduced by V beta 3-(57-77). These data suggest that the region of V beta 3 encompassing amino acids 57-77 is an area that displays the appropriate sequence and conformation for binding of the SEA molecule and blocking of the resultant interaction with the T-cell antigen receptor. PMID- 1502192 TI - Stable genetic transformation of a beneficial arthropod, Metaseiulus occidentalis (Acari: Phytoseiidae), by a microinjection technique. AB - A microinjection technique has resulted in stable transformation of the western predatory mite Metaseiulus occidentalis. Early preblastoderm eggs within gravid females were microinjected. The needle was inserted through the cuticle of gravid females into the egg, or the tissue immediately surrounding the egg. This maternal injection method resulted in relatively high levels of survival and transformation. Transformation was achieved without the aid of any transposase producing helper plasmid. The predatory mite was transformed with a plasmid containing the Escherichia coli beta-galactosidase gene (lacZ) regulated by the Drosophila hsp70 heat-shock promoter. Putatively transformed lines were isolated based on beta-galactosidase activity in first-generation larvae. Transformation was confirmed in the sixth generation by polymerase chain reaction amplification of a region spanning the Drosophila/E. coli sequences. Amplification of a nested region, also spanning the interspecific boundary, provided further evidence for stable transformation. Maternal microinjection may be adaptable to other beneficial arthropods, particularly other phytoseiid mites. Genetic transformation of M. occidentalis may improve its efficiency as a biological control agent as well as provide a method for investigating details of its physiology and ecology. PMID- 1502193 TI - Phosphorylation stimulates the transcriptional activity of the human beta 1 thyroid hormone nuclear receptor. AB - The role of phosphorylation on the gene activation activity of the human beta 1 thyroid hormone nuclear receptor (h-TR beta 1) was examined. h-TR beta 1 was found to be a phosphoprotein when expressed in COS-1 cells, with serine, threonine, and tyrosine (85:10:5) as the phosphorylation sites. Okadaic acid (a potent inhibitor of phosphatases 1 and 2A) at 0.1, 0.25, and 0.5 microM increased the phosphorylation of h-TR beta 1 by 3-, 7-, and 11-fold, respectively. The increase in phosphorylation was accompanied by a concomitant increase in phosphorylation was accompanied by a concomitant increase in receptor-mediated transcription in transient transfection assays. h-TR beta 1 purified from Escherichia coli was phosphorylated in vitro by the endogenous kinase from cellular extracts. Serine, threonine, and tyrosine were phosphorylated in a similar ratio to that found in COS-1 cells. The in vitro phosphorylation was stimulated by okadaic acid. Phosphorylation did not affect the binding of h-TR beta 1 to 3,3',5-triiodo-L-thyronine. However, phosphorylation of h-TR beta 1 resulted in an increase of its binding to DNA and conferred on it the ability to bind to nuclear accessory proteins. The results indicate that phosphorylation plays an important role in the transcriptional activity of h-TR beta 1. PMID- 1502194 TI - Correlating genetic variation in carbon isotopic composition with complex climatic gradients. AB - Genetic variation in both carbon isotope discrimination and the proportions of leaf and photosynthetic twig tissues were observed in ecotypes of Hymenoclea salsola T.G., a common shrub in the deserts of the western United States, when grown under common garden conditions. These variations were correlated with climatic conditions in the habitats of origin through a model that described the leaf-to-air water vapor gradients experienced by plants during the growing season. Both carbon isotope discrimination and the proportion of leaves in the canopy were lower in plants derived from habitats with higher leaf-to-air vapor gradients, despite the fact that some of these sites received relatively high amounts of annual precipitation. These patterns were consistent with the notion that plants are able to maintain substantial control of water-use efficiency over large environmental gradients of temperature and moisture availability. PMID- 1502195 TI - Interleukin 1 regulates secretion of zinc-thymulin by human thymic epithelial cells and its action on T-lymphocyte proliferation and nuclear protein kinase C. AB - Thymic epithelial cells (TEC) are known to secrete thymic hormones that influence maturation of T lymphocytes. One of these peptides, thymulin, requires zinc in an equimolar ratio for biological activity. A previous study [Cousins, R. J. & Leinart, A. S. (1988) FASEB J. 2, 2884-2890] showed that interleukin 1 (IL-1) in vivo stimulates zinc uptake by the thymus. Both the alpha and beta forms of IL-1, which stimulate proliferation of human TEC, also stimulate their uptake of zinc in vitro, and this latter stimulation is both dependent and independent of proliferation. Zinc induces zinc accumulation without proliferation. Two other stimulants of proliferation, bovine pituitary extract and epidermal growth factor, stimulate zinc uptake by TEC, but only in a manner dependent on proliferation. Utilizing in situ hybridization, we show that the IL-1 alpha and beta forms and zinc induce metallothionein mRNA expression TEC. Metallothionein is thought to be involved in the transfer of zinc to thymulin. IL-1 was shown to stimulate the secretion of thymulin as measured both by its ability to stimulate induction of IL-2 receptor-positive lymphocytes from human peripheral blood lymphocytes and by the azathioprine-sensitive rosette assay. In addition, the zinc-thymulin complex in the presence, but not absence, of IL-1 stimulates nuclear protein kinase C in isolated lymphocyte nuclei. IL-1 apparently regulates the synthesis or secretion and delivery of zinc-thymulin complex to the T lymphocyte system. PMID- 1502196 TI - Induction of immunity and oral tolerance with polymorphic class II major histocompatibility complex allopeptides in the rat. AB - We studied the immunogenicity and tolerogenicity of class II major histocompatibility complex (MHC) allopeptides in the rat. Inbred LEW (RT1l) rats, used as responders, were immunized in the foot pad with a mixture of eight synthetic class II MHC allopeptides emulsified in complete Freund's adjuvant. These sequences represent the full-length second domain of RT1.Bu and RT1.Du (WF) beta chains. In vitro, responder lymphocytes harvested from popliteal and inguinal lymph nodes of immunized animals exhibited significant proliferation to the MHC allopeptide mixture. In addition, these responder lymphocytes had significantly increased proliferation to allogeneic WF (RT1u) stimulator cells, when compared to naive controls in the standard one-way mixed lymphocyte response. In vivo, peptide-immunized LEW animals were challenged in the ear 2 weeks after immunization with the allopeptide mixture, the individual allopeptide sequences, or allogeneic WF splenocytes. When compared to controls, these animals had significant delayed-type hypersensitivity responses to the allopeptide mixture, to the beta-pleated sheet allopeptide sequences, and to allogeneic WF splenocytes but not to the alpha-helix allopeptide sequences, to syngeneic LEW splenocytes, or to third party allogeneic BN splenocytes. Oral administration of the allopeptide mixture to LEW responder rats daily for 5 days before immunization effected significant reduction of delayed-type hypersensitivity responses both to the allopeptide mixture and to allogeneic splenocytes. This reduction was antigen-specific, since there was no reduction of delayed-type hypersensitivity responses to mycobacterium tuberculosis. These data demonstrate that lymphocytes from animals immunized with polymorphic class II MHC allopeptides can recognize and proliferate to the same amino acid sequences on allogeneic cell surface MHC molecules. In addition, oral administration of these peptides down-regulates the systemic cell-mediated immune response in a specific fashion. Synthetic MHC allopeptides should allow the study of alloimmunity in vivo, including induction of immune tolerance. PMID- 1502197 TI - Adenovirus-human immunodeficiency virus (HIV) envelope recombinant vaccines elicit high-titered HIV-neutralizing antibodies in the dog model. AB - Recombinant human adenoviruses (Ads) (types 4, 5, and 7) expressing the HIV-1 envelope membrane glycoprotein (gp160) were tested for immunogenicity in the dog. Administration of recombinant Ad7-env by intratracheal inoculation resulted in a low serum antibody response to gp160, which developed over several weeks. A strong neutralizing antibody response to the Ad7 vector developed within 1 week of infection. A subsequent booster inoculation 12 weeks later with the heterotypic Ad4-env recombinant virus resulted in significantly enhanced humoral responses directed at the envelope antigen, as measured by both ELISA and Western blot analysis as well as high-titer type-specific neutralizing antibodies, with some animals achieving neutralization titers approaching 1000. Recombinant HIV envelope glycoprotein derived from Ad-HIV-infected cell cultures was used as a subunit booster injection for dogs that had previously received sequential immunizations with heterotypic recombinant Ads. Significant immune responses against the envelope developed as measured by ELISA, Western blot analysis, and neutralization assays. These data indicate that live recombinant Ad-HIV vaccines are capable of inducing high-titer type-specific neutralizing antibodies to gp160 in vivo. Recombinant HIV envelope glycoprotein subunit vaccines, prepared from Ad env-infected cells, are capable of boosting these responses. PMID- 1502198 TI - Dopamine transporter site-directed mutations differentially alter substrate transport and cocaine binding. AB - Polar amino acids lying within three hydrophobic regions of the dopamine transporter (DAT) are analogous to those important for ligand recognition by catecholamine receptors. Possible functional significance of these amino acids was examined by expressing DAT cDNAs mutated in these polar residues. Replacement of aspartate at position 79 with alanine, glycine, or glutamate dramatically reduced uptake of [3H]dopamine and the tritium-labeled Parkinsonism-inducing neurotoxin 1-methyl-4-phenylpyridinium (MPP+) and reduced the mutants' affinity for the tritium-labeled cocaine analog (-)-2 beta-carbomethoxy-3 beta-(4 fluorophenyl)tropane (CFT) without affecting Bmax. Replacement of the serine residues at positions 356 and 359 in the seventh hydrophobic region by alanine or glycine caused reductions in [3H]dopamine and [3H]MPP+ uptake, whereas [3H]CFT binding was less affected. Substitution of two serines in the eighth hydrophobic region yielded wild-type values for [3H]dopamine and [3H]MPP+ uptake and [3H]CFT binding. These results demonstrate that aspartate and serine residues lying within the first and seventh hydrophobic putative transmembrane regions are crucial for DAT function and provide identification of residues differentially important for cocaine binding and for dopamine uptake. PMID- 1502200 TI - An algorithm for protein engineering: simulations of recursive ensemble mutagenesis. AB - An algorithm for protein engineering, termed recursive ensemble mutagenesis, has been developed to produce diverse populations of phenotypically related mutants whose members differ in amino acid sequence. This method uses a feedback mechanism to control successive rounds of combinatorial cassette mutagenesis. Starting from partially randomized "wild-type" DNA sequences, a highly parallel search of sequence space for peptides fitting an experimenter's criteria is performed. Each iteration uses information gained from the previous rounds to search the space more efficiently. Simulations of the technique indicate that, under a variety of conditions, the algorithm can rapidly produce a diverse population of proteins fitting specific criteria. In the experimental analog, genetic selection or screening applied during recursive ensemble mutagenesis should force the evolution of an ensemble of mutants to a targeted cluster of related phenotypes. PMID- 1502199 TI - Species specificity of renin kinetics in transgenic rats harboring the human renin and angiotensinogen genes. AB - The renin-angiotensin system (RAS) is the most important regulatory system of electrolyte homeostasis and blood pressure. We report here the development of transgenic rats carrying the human angiotensinogen TGR-(hAOGEN) and human renin TGR(hREN) genes. The plasma levels and tissue distribution of the transcription and translation products from both genes are described. A unique species specificity of the enzyme kinetics was observed. The human RAS components in the transgenic rats did not interact with the endogenous rat RAS in vivo. Instead, infusions of exogenous human RAS components specifically interacted with human transgene translation products. Thus, infusion of human renin in TGR(hAOGEN) led to an increase of angiotensin II and an elevation of blood pressure, which could not be antagonized by the human-specific renin enzyme inhibitor Ro 42-5892. Rat renin also elevated blood pressure and angiotensin II in TGR(hAOGEN); however, this effect was not antagonized by the human renin inhibitor. Compared to mice, rats offer the advantage of chronic instrumentation and repetitive, sophisticated, hemodynamic, and endocrinological investigations. Thus, transgenic rat models with human-specific enzyme kinetics permit primate-specific analyses in non-primate in vivo and in vitro experimental systems. PMID- 1502201 TI - The intrinsic helix-forming tendency of L-alanine. AB - Conformational energy calculations have been carried out for three hexadecapeptides in water--namely, a copolymer with the sequence acetyl-AAAAKAAAA KAAAAKA-amide, 3K(I), in both the charged and neutral forms; a neutral peptide with the sequence acetyl-AAQAAAAQAAAAQAAY-amide, AQY; and a 16-residue L-alanine homopolymer with acetyl and amide terminal groups. The conformational energy was a sum of the empirical conformational energy program for peptides (ECEPP/2) potential energy plus continuum hydration free energy. An empirical (JRF) parameter set was used for the hydration free energy, together with an electrostatic contribution to the solvent effect from charged lysines. The computed relatively high helix content of the most probable conformation of charged 3K(I) and the intermediate helix content of AQY agree reasonably well with experimental values. The computed very low helix content of the alanine homopolymer agrees with experiments on block copolymers and on host-guest random copolymers. The calculations suggest that the high helix content computed for 3K(I) is due to the sum of internal and hydration free energies of the lysine residues rather than to a high intrinsic helix-forming tendency of alanine. The principal component lowering the computed helix contents of AQY and the alanine copolymer relative to 3K(I) is hydration. PMID- 1502202 TI - NF-kappa B-dependent induction of the NF-kappa B p50 subunit gene promoter underlies self-perpetuation of human immunodeficiency virus transcription in monocytic cells. AB - The molecular mechanisms underlying the sustained nuclear translocation of NF kappa B observed in U937 monocytic cells chronically infected with human immunodeficiency virus (HIV) were studied. The activity of the promoter regulating the synthesis of the p105 precursor of the NF-kappa B p50 subunit was enhanced in these cells. Deletions in this promoter indicated that this upregulation was mediated through the NF-kappa B- but not the AP-1-binding motif, by bona fide p50/p65 heterodimers. Analysis of cytosolic extracts indicated that NF-kappa B levels were increased in HIV-infected cells. In contrast to the transient NF-kappa B activation induced by phorbol ester, the permanent NF-kappa B translocation induced by HIV infection was not dependent on PKC isoenzymes alpha and beta as shown by the use of a specific inhibitor (GF 109203X). These observations indicate that during chronic HIV infection of U937 cells, continuous NF-kappa B (p50/p65) translocation results in p105 promoter upregulation with subsequent cytosolic NF-kappa B accumulation, ready for further translocation. This HIV-mediated mechanism results in a self-perpetuating loop of NF-kappa B production. PMID- 1502203 TI - Proteins of transcription factor ISGF-3: one gene encodes the 91-and 84-kDa ISGF 3 proteins that are activated by interferon alpha. AB - ISGF-3 is an interferon-dependent positive-acting transcription factor that is cytoplasmically activated, possibly through direct interaction with the interferon receptor. The factor has been purified, its component proteins have been separated, and its peptide sequences have been obtained. From the sequences, degenerate oligonucleotide probes were constructed to screen for cDNA clones. Sequencing of the selected clones shows that the 91- and 84-kDa components represent two forms of a previously unknown (to our knowledge) protein. Several antibodies raised against these proteins prove that they indeed do encode protein components of ISGF-3. This work provides reagents to explore the modification of this cytoplasmically activated transcription factor. PMID- 1502204 TI - The proteins of ISGF-3, the interferon alpha-induced transcriptional activator, define a gene family involved in signal transduction. AB - ISGF-3 is a multiprotein transcription factor that is very quickly activated in the cell cytoplasm only after attachment of interferon alpha to the cell surface. To understand the specific cytoplasmic activation of proteins that move to the nucleus and direct increased transcription of specific genes, we have purified and now report completion of the cloning of cDNA encoding the four proteins of ISGF-3. With all of the sequences available, it is clear that three of these proteins are encoded by members of a previously unrecognized gene family. We suggest that proteins encoded by this gene family serve the function of interpreting the fact that a cell surface receptor has bound its ligand so that specific signal transduction to the nucleus can occur. PMID- 1502205 TI - Extensive variation in evolutionary rate of rbcL gene sequences among seed plants. AB - Extensive variation in synonymous and nonsynonymous rates of substitution was observed among 50 sequences of the gene coding for the large subunit of ribulose 1,5-bisphosphate carboxylase (rbcL) representing bryophyte, conifer, dicot, and monocot taxa. Relative rate tests revealed rate differences of up to 138% for nonsynonymous substitutions and up to 85% for synonymous ones. Within angiosperms, the annual forms evolved more rapidly, on average, than perennial forms. This rate heterogeneity was more extensive at nonsynonymous sites than synonymous ones, and it resulted primarily from a recent acceleration of substitution rate in many groups of angiosperms. PMID- 1502206 TI - Heparin-binding growth factor 1 induces the formation of organoid neovascular structures in vivo. PMID- 1502207 TI - Role for sympathetic nerves and mast cells in vasodilation induced by primary afferent nerves. PMID- 1502208 TI - Renal and metabolic clearances of sulfamethoxazole in Mexican healthy subjects. PMID- 1502209 TI - Pharmacokinetics of pelanserin in healthy volunteers. PMID- 1502211 TI - Pharmacological properties of acetylcholine mediated relaxation of the human umbilical artery. PMID- 1502210 TI - Gastrointestinal prokinetic activity of serotonergic agents. PMID- 1502212 TI - A new spectrophotometric assay for cholinesterase activity. PMID- 1502213 TI - Oxygen radical generation and alkylating ability of mitomycin C bioactivated by xanthine dehydrogenase. PMID- 1502214 TI - Effects of the bromophenyl-dihidro-2H-1,5-benzodiazepine-2-thione on sleep. PMID- 1502215 TI - Effect of atropine sulphate on sleep of the iguanid lizard Ctenosaura similis. PMID- 1502216 TI - The simultaneous measurement of uric acid and ascorbic acid in the lateral ventricles of freely moving rats by brain microdialysis and electrochemical detection. PMID- 1502218 TI - A model for the K+ channel pore based on close packing of helices with substantial tryptophan bulk. PMID- 1502217 TI - Microdialysis measurement of striatal dopamine levels in freely moving rats after cocaine or amphetamine treatment. PMID- 1502219 TI - The importance of K+ channel rectification to cardiac repolarization. PMID- 1502220 TI - Effects of hypertension and ageing on vascular reactivity and associative learning. PMID- 1502221 TI - Antagonism of the lethal effects of cyanide with rhodanese containing murine carrier erythrocytes. PMID- 1502222 TI - Anticonvulsant effect of the 7-(p-chlorophenyl)-8-phenoxy-4,5-benzo-3-aza-2 nonem. PMID- 1502223 TI - Comparative study of intramuscularly administered ketorolac and nalbuphine in patients with pain following orthopedic surgery. PMID- 1502224 TI - Experimental tension headache in humans: a double blind comparison of the analgesic effect of dipyrone, naproxen plus paracetamol or placebo. PMID- 1502225 TI - Evaluation of the analgesic efficacy of a combination of naproxen and paracetamol versus dipyrone on the tourniquet test in healthy volunteers. PMID- 1502226 TI - Are there monoaminergic mechanisms in sleep regulation in reptiles? PMID- 1502227 TI - Naproxen effects during acute inflammation produced by Staphylococcus aureus and by thinner structural study. PMID- 1502228 TI - Allosterism and drug action. PMID- 1502229 TI - Effect of 5-hydroxytryptamine agonists and antagonists on cholera toxin induced intestinal fluid accumulation in conscious rats. PMID- 1502230 TI - Rat esophagus anaphylaxis. PMID- 1502231 TI - Irreversible effects of 4-DAMP mustard on muscarinic receptors in vivo. PMID- 1502232 TI - MPTP treatment decreases striatal copper content in mice. PMID- 1502233 TI - Comparison of the effect of isoquinoline analogs and propranolol on voluntary ethanol ingestion. PMID- 1502234 TI - Partially protective effect of amantadine in the MPTP model of Parkinson's disease. PMID- 1502235 TI - Copper plus ascorbate inactivates lactate dehydrogenase: are oxygen radicals involved? PMID- 1502236 TI - Ultrastructural changes in photoreceptors and retinal layers of the mouse fetus exposed to diazepam. PMID- 1502237 TI - Effects of prenatal administration of diazepam on the cerebral cortex of adult mice. PMID- 1502238 TI - Pharmacokinetic/pharmacodynamic analysis of the interaction between acetaminophen and caffeine. PMID- 1502239 TI - The biomethylation of sodium arsenate by rat liver cytosol determined by mass spectrometry. PMID- 1502240 TI - Morphological and functional changes in WRL-68 cells treated with heavy metals. PMID- 1502241 TI - Cytotoxicity of inorganic and organic arsenics in cell culture. PMID- 1502242 TI - Novel non-peptide angiotensin II receptor antagonists. PMID- 1502243 TI - Effects of RS-59022-198 on the uptake and release of norepinephrine in isolated rat hearts. PMID- 1502244 TI - Protective effect of perfluorocytylbromide emulsions on a cardioplegic model of reperfusion injury. PMID- 1502245 TI - Cerebral vessels in spasm show an enhanced response to calmodulin antagonists. PMID- 1502247 TI - Monthly Prostaglandin Bibliography prepared by the University of Sheffield Biomedical Information Service. PMID- 1502246 TI - Comparative effects of the K+ channel openers, pinacidil and cromakalim on vascular tone: sensitivity to glyburide and calcium. PMID- 1502248 TI - Enhancement of prostaglandin E2 production by liver macrophages (Kupffer cells) after stimulation with biological response modifiers. AB - PGE2 production by liver macrophages (Kupffer cells) activated by biological response modifiers was examined. Kupffer cells obtained from a normal rat liver possessed cyclooxygenase activity and produced TXB2, PGD2, and PGE2 from (1 14C)arachidonic acid. The major product was PGD2. When Kupffer cells were incubated in the presence of lipo-polysaccharide (LPS), OK-432, or heat-killed Propionibacterium acnes for 24 h, the amount of arachidonate cyclooxygenase products increased and the major product changed from PGD2 to PGE2. When liver macrophages including Kupffer cells were prepared from rats after an injection of LPS, OK-432, or heat-killed P. acnes, it was noticed that the number of cells obtained and PGE2 production increased compared with those of normal rat. These results suggested that PGE2 production by rat liver was induced when they were treated with biological response modifiers. PMID- 1502249 TI - The influence of dietary essential fatty acids on uterine C20 and C22 fatty acid composition. AB - The effect of dietary fatty acids on uterine fatty acid composition was studied in rats fed control diet or semi-synthetic diet supplemented with 1.5 microliter/g/day evening primrose oil (EPO) or fish oil (FO). Diet-related changes in uterine lipid were detected within 21 days. Changes of 2- to 20-fold were detected in the uterine n-6 and n-3 essential fatty acids (EFA) and in certain saturated and monounsaturated fatty acids. The FO diet was associated with higher uterine C20 and C22 n-3, and the EPO diet, with higher uterine n-6 fatty acid. High uterine C18:2 n-6 was detected in neutral lipid (NL) of rats fed high concentrations of this fatty acid, but there was little evidence of selective incorporation or retention of C18:2 n-6 by uterine NL. The incorporation of EFA into uterine phospholipids (PL) was greater than NL EFA incorporation, and uterine PL n-3/n-6 ratios showed greater diet dependence. Tissue/diet fatty acid ratios in NL and PL also indicated preferential incorporation/synthesis of C16:1 n-9, and C16:0, and there was greater incorporation of C12:0 and C14:0 into uteri of rats fed EPO and FO. Replacement of 50-60% of arachidonate with n-3 EFA in uterine PL may inhibit n-6 EFA metabolism necessary for uterine function at parturition. PMID- 1502250 TI - Correlation between dysmenorrheic severity and prostaglandin production in women with endometriosis. AB - The role of prostaglandins (PGs) in dysmenorrhea of endometriosis is poorly understood. The relationship between dysmenorrheic severity and prostaglandin production was investigated in endometriosis. Slices of normal myometrium, adenomyosis, normal ovary and endometrial cyst were incubated. 6-Keto-PGF1 alpha (a metabolite of PGI2), TXB2 (a metabolite of TXA2), PGF2 alpha, and PGE2 concentrations of the incubation medium were measured by RIA. The results showed that 6-keto-PGF1 alpha production in adenomyosis and endometrial cyst were significantly higher than those in normal myometrium and ovary. A direct relationship between the degree of dysmenorrheic severity and PGs production in tissue in endometriosis was observed. PMID- 1502251 TI - Selective growth inhibition of a human malignant melanoma cell line by sesame oil in vitro. AB - Ayurveda, an ancient and comprehensive system of natural medicine, recommends regular topical application to the skin of sesame oil, above all other oils, as a health-promoting procedure. We examined the effect of sesame oil and several other vegetable oils and their major component fatty acids on the proliferation rate of human normal and malignant melanocytes growing at similar rates in serum free media. We found that sesame and safflower oils, both of which contain large amounts of linoleate in triglyceride form, selectively inhibited malignant melanoma growth over normal melanocytes whereas coconut, olive and mineral oils, which contain little or no linoleate as triglyceride, did not. These oils were tested at a range of 10-300 micrograms/ml. We found that of the fatty acids tested, only linoleic acid was selectively inhibitory while palmitic and oleic were not. These fatty acids were tested in the range of 3-100 micrograms/ml. These results suggest that certain vegetable oils rich in linoleic acid, such as the sesame oil, recommended for topical use by Ayurveda, may contain selective antineoplastic properties which are similar to those demonstrated for essential polyunsaturated fatty acids and their metabolites. This suggests that whole vegetable oils may have potential clinical usefulness. PMID- 1502252 TI - Synthesis of prostaglandin F2 alpha, E2 and prostacyclin in isolated corpora lutea of adult pseudopregnant rats throughout the luteal life-span. AB - The ability of de novo biosynthesis of prostaglandins (PGs) in individual whole corpora lutea (CL) obtained from sterile-mated adult pseudopregnant rats on different days of the luteal phase and the post-luteolytic period was evaluated. Production of PGs, progesterone and 20 alpha-dihydroprogesterone were determined after in vitro incubation of CL extirpated from Day 2 to Day 19 after mating. A time-relationship with increased accumulation of PGs in the medium was demonstrated from 18 s to 5 h, with large increments during the first 30 min. Basal accumulation of PGs in the incubation medium was highest for 6-keto-PGF1 alpha (the stable metabolite of prostacyclin) greater than PGE2 greater than PGF2 alpha greater than thromboxane B2 (TXB2) and basal accumulation of PGF2 alpha and PGE2 measured in the medium was maximal on Day 10-11 of pseudopregnancy, concomitantly with a decline in secretion of progesterone. Addition of arachidonic acid (AA) dose-dependently increased synthesis of PGs, with absolute amounts of PGE2 greater than 6-keto-PGF1 alpha greater than PGF2 alpha greater than TXB2 and addition of 14 microM indomethacin markedly inhibited accumulation of all PGs measured. Luteinizing hormone (LH, 10 micrograms/ml) stimulated progesterone secretion on all days during pseudopregnancy, but not on the post luteolytic Day 19. LH increased PGF2 alpha, PGE2 and 6-keto-PGF1 alpha secretion on Day 13 of pseudopregnancy by 76%, 91% and 28%, respectively, but not on the other days tested. Furthermore, stimulation of PG-synthesis by addition of AA abrogated the LH-induced progesterone accumulation markedly, but only on Day 13 of pseudopregnancy. Epinephrine (5 micrograms/ml) increased production of progesterone and also PGs, but only on Day 2 of pseudopregnancy, whereas oxytocin (100 mIU/ml) was found to be without effect on progesterone as well as PG secretion on all days tested. The results of the present study demonstrates the independent ability of the rat CL to synthesize PGG/PGH2-derived prostaglandins, including the putative luteolysin PGF2 alpha. Secondly, we demonstrate that LH and AA-induced increases in PGF2 alpha and PGE2 production during the luteolytic period, may be an autocrine or paracrine mechanism involved in luteolysis. PMID- 1502253 TI - Studies on the involvement of prostaglandins in implantation in the rat. PMID- 1502254 TI - Cigarette smoking and platelet-vessel wall interactions. PMID- 1502255 TI - Effect of n-3 and n-6 dietary fats on the lipoxygenase products from stimulated rat neutrophils. AB - Fish oil was fed to rats in combination with an equal amount of olive, sunflower or linseed (flax) oil in semisynthetic diets for 3 weeks. Following stimulation of isolated neutrophils with calcium ionophore the levels of leukotrienes (LT) were determined by HPLC. Graphical presentation of the resultant data show a direct linear relationship between LTB production and substrate concentration with no preferential conversion of n-3 or n-6 substrates. In addition the results highlighted the greater conversion of eicosapentaenoic acid (EPA) and arachidonic acid (AA) to 5-hydroxy metabolites in stimulated neutrophils. There is no suggestion in our results of inhibition of any of the enzymatic conversion steps between EPA or AA and LTB production by any of the dietary fatty acids except by altering the EPA/AA ratio in neutrophil membranes. PMID- 1502256 TI - Changes in ovarian NAD(+)-dependent 15-hydroxyprostaglandin dehydrogenase activity in pregnant and pseudopregnant rabbits. AB - The specific activity of NAD(+)-dependent 15-hydroxyprostaglandin dehydrogenase (PGDH) was found to increase in the ovaries of pregnant and pseudopregnant rabbits. The mean specific activity of cytosolic ovarian PGDH in 14- to 28-day pregnant rabbits was 24.3 +/- 8.1 nmol NADH formed/min/mg protein (n = 16) using PGE1 as substrate whereas in nonpregnant rabbits the specific activity was 1.5 +/ 0.8 nmol NADH formed/min/mg protein (n = 8). The reaction was dependent on NAD+; NADP+ did not support the reaction. In grouping the PGDH activities from pregnant rabbits into second (14-18 days) and third (2-28 days) trimester periods, no significant difference between values was found (26.1 +/- 8.9 vs 23.4 +/- 8.1 nmol NADH formed/min/mg protein, respectively). Western blot analysis of the ovarian cytosol using an antibody which was made to the purified lung PGDH of pregnant rabbits recognized an ovarian protein of identical molecular mass (30 kDa). Ovarian PGDH activities were also examined in rabbits treated with pregnant mare's serum gonadotrophin (PMSG) and human chorionic gonadotrophin (hCG) to induce a state of superovulatory/pseudopregnancy and only on day 11 following hCG treatment was an increase in PGDH specific activity observed. On day 11, the specific activity was 14.8 +/- 4.3 nmol NADH formed/min/mg protein whereas values on days 10 and 12 were only 1.1 +/- 1.1 and 1.0 +/- 0.8, respectively. PGDH activities on days 3, 7 and 16 were also low.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1502257 TI - Abnormal response of urinary eicosanoid system to norepinephrine infusion in patients with essential hypertension. AB - To define the role of the renal eicosanoid system in sustaining renal homeostasis in hypertension, we investigated the alterations in urinary excretions of 6-keto prostaglandin F1 alpha (6-keto-PGF1 alpha), a stable metabolite of vasodepressor prostacyclin, and thromboxane B2 (TXB2), a stable metabolite of vasoconstrictor TXA2, when norepinephrine was continuously infused for 90 min in hypertensive (n = 13) and normotensive subjects (n = 14). There was no difference in plasma norepinephrine concentration after the infusion between the hypertensive and the normotensive subjects. Moreover, the percent changes in renal vascular resistance elicited by norepinephrine in the hypertensives were equal to those of the normotensive subjects. In the normotensive subjects, the norepinephrine infusion significantly increased urinary 6-keto-PGF1 alpha excretion and decreased urinary excretion of TX, both of which are beneficial for sustaining renal function. In fact, the greater the production of renal 6-keto-PGF1 alpha was, the less the reduction of renal blood flow and urinary sodium excretion was. In the hypertensive subjects, however, these normal responses of the renal eicosanoid system, seen in the normotensives, were abolished; urinary 6-keto-PGF1 alpha was unaltered and thromboxane generation was rather increased. Thus, the renal eicosanoid system dysfunctions in hypertensive subjects when the renal circulation is challenged by norepinephrine. These abnormal responses are likely to cause sodium retention and could contribute, in part, to the hypertensive mechanism in patients with essential hypertension. PMID- 1502258 TI - Resonance Raman and surface-enhanced resonance Raman spectroscopy of hypericin. AB - Hypericin has been found to exhibit a variety of photodynamic effects. To correlate biological activity with molecular structure, complete physical characterization of hypericin is required. The vibrational spectrum has been determined and resonance Raman and surface enhanced resonance Raman scattering spectra are reported. In addition, the Raman spectrum of a model compound has been studied to facilitate assignment of the vibrational modes of hypericin. PMID- 1502259 TI - A new fluorescent cholesterol derivative: structure and blood plasma analysis. AB - A fluorescent cholesterol derivative produced by reaction with gaseous HCl and zinc chloride in ethyl acetate is shown to be a chlorine substituted B-ring diene. The species forms relatively rapidly via an i-steroid rearrangement, requiring a temperature around 70 degrees C. A weak, possibly dimeric pi-allyl zinc complex exists in solution, leading to a red shift in the fluorescence emission. The application of the derivative to the determination of cholesterol in bovine plasma provides good sensitivity and precision and requires notably small sample volumes. PMID- 1502261 TI - Retention and phototoxicity of tetra(4-sulfonatophenyl)porphine in cultivated human cells. The effect of fractionation of light. AB - Human cervix carcinoma cells of the line NHIK 3025 were incubated for 18 h with tetra(4-sulfonatophenyl)porphine (TPPS4) and further incubated for 1-29 h in sensitizer free medium before exposure to light. After 1 h in sensitizer free medium only a 20% further loss of TPPS4 was observed within the next 28 h. During the time in sensitizer free medium, each TPPS4 molecule became more efficient in sensitizing single cells to photoinactivation. This enhanced photosensitizing efficiency of TPPS4 correlated well with the enhanced fluorescence yield of TPPS4. In some experiments the cells were exposed to a light dose inactivating 10% of the cells after incubation for 1 h in sensitizer free medium and a second graded light dose given 4-28 h later. Exposure of the cells to the first light dose led to loss of 60% of TPPS4 from the cells. Despite the significant loss of sensitizer from the cells the fluorescence yield of TPPS4 from each cell was found to increase (e.g. by 100% 4 h after light exposure). The enhanced fluorescence yield of cell bound TPPS4 was followed by a 1.6-2.5-fold increase in sensitivity of each cell to second light dose. Thus, a small light dose increased the photosensitivity of TPPS4-loaded NHIK 3025 cells for several hours after the first light exposure. The advantageous effect of light fractionation was reduced by a significantly enhanced loss of sensitizer induced by the first light exposure. The optimal time between the two fractions of light seems to be 30-90 min. PMID- 1502260 TI - Action spectra of phthalocyanines with respect to photosensitization of cells. AB - Human carcinoma cells (NHIK 3025 cells) and Chinese hamster cells (V79 cells) were incubated with AlPcS1, AlPcS2 and AlPcS4, phthalocyanines with different lipophilicity but with similar photochemical properties when in monomeric solutions. The absorption- and fluorescence spectra of the dyes in the cells were recorded as well as their action spectra with respect to sensitizing cells to photoinactivation. These spectra show that under the present conditions AlPcS1 is strongly aggregated in both cell lines; AlPcS2 is aggregated in V79 cells but much less so in NHIK 3025 cells. A main finding is that the shapes of the action spectra are similar to that of the fluorescence excitation spectra, but not to the absorption spectra, indicating that the photosensitizing effects of the dyes are mainly due to their monomeric fraction in the cells. AlPcS2 and AlPcS4 localize intracellularly mainly in lysosomes while AlPcS1 was found to be more diffusely distributed in cells. As measured per quantum of fluorescence emitted, AlPcS1 and AlPcS2 are more efficient sensitizers than AlPcS4. The difference in efficiency between AlPcS2 and AlPcS4 is supposedly due to a different localization pattern on the suborganelle level. PMID- 1502262 TI - Psoralens cleave pBR322 DNA under ultraviolet radiation. AB - Supercoiled (SC) pBR322 was used to probe the recent claim that 5 geranoxylpsoralen (5-GOP) did not photoreact with DNA. Contrary to expectations, 5-GOP was found to damage DNA in the presence of UV-A through two competing pathways: (a) single strand breaks, identified by the conversion of supercoiled into open circular and linear DNA, and (b) cross-linking, revealed by the fluence dependent decrease in the extent of denaturation of the double stranded supercoiled DNA to single stranded circular DNA. In addition, a fluence-dependent modification reduced the ability of the restriction enzyme EcoR I to linearize the photosensitized DNA, and alkali-labile lesions were generated. Psoralen, 5 methoxypsoralen, and 8-methoxypsoralen, which are well-known to undergo cycloaddition to DNA, had a more pronounced effect on supercoiled DNA. Single strand breaks occurred more readily than with 5-GOP, and the surviving SC form remaining had reduced electrophoretic mobility in agarose gels. In all cases, the DNA damage was more prominent when oxygen was absent. PMID- 1502263 TI - Influence of dietary omega-6, -3 fatty acid sources on the initiation and promotion stages of photocarcinogenesis. AB - To determine the segment along the carcinogenic continuum at which dietary lipid exerts its principal effect, six groups of 35 Skh-HR-1 hairless mice were placed on defined isocaloric diets containing either 0.75%, 12% corn oil or 12% menhaden oil as sources of omega-6 or omega-3 fatty acids, respectively. All animals received an 11 week course of UV-radiation from fluorescent sunlamps. Upon termination of UV, diets of some groups were crossed-over to either low fat, high fat, omega-6 or omega-3 fatty acid sources. The first tumor appeared at week 14. Life-table analysis of the tumor incidence curves and Wilcoxon tests of tumor multiplicity provided evidence that high corn oil diets significantly (P less than 0.01) enhance carcinogenic expression; that tumor enhancement by the omega-6 fatty acid source occurs during the post-initiation, or promotion, stage; that replacement with a low corn oil diet after UV-initiation will negate the exacerbating effect of high corn oil; and that an omega-3 fatty acid source inhibits UV-carcinogenesis even at high dietary levels, although not during the post-initiation stage. PMID- 1502264 TI - Photosensitization of MCF-7 cells with diaziquone using visible light: correlation with DNA strand breaks and free radical production. AB - The ability of visible light to enhance the activity of diaziquone (AZQ) was evaluated in MCF-7 human breast cancer cells. MCF-7 cells were sensitive to AZQ, while visible light illumination had no appreciable effect on cell survival. In the presence of AZQ, visible light potentiated AZQ's cytotoxicity. This potentiation of AZQ activity correlated with a 2-2.5-fold increase in the formation of free radicals (hydroxyl radicals and AZQ semiquinone) and with the production of DNA strand breaks as measured by electron paramagnetic resonance and gel electrophoresis respectively. These results support the hypothesis that free radical formation is part of the mechanism of action of AZQ. PMID- 1502265 TI - Mechanisms of citral phototoxicity. AB - Citral, a monoterpene aldehyde synthesized by several plant genera, has been reported to exhibit antimicrobial activity. For the first time, we report that critral exhibits UV-A (315-400 nm) light enhanced oxygen-dependent toxicity against a series of Escherichia coli strains differing in DNA repair and catalase proficiency. Those E. coli strains carrying a gene leading to catalase deficiency (katF) are particularly sensitized to inactivation by citral and UV-A treatment when compared to catalase proficient strains (katF+). Consistent with these in vivo observations, citral when treated with UV-A in vitro produces H2O2. When tested against Fusarium oxysporum and F. solani, fungal root pathogens of Citrus, enhanced toxicity by citral in the presence of UV-A was demonstrated, while dark toxicity was negligible. When the plasmid pBR322 was treated with citral in the presence of UV-A, a change in conformation from the covalently closed circular to the open circular and, ultimately, the linear form was observed. The change in plasmid conformation corresponded to a reduction in transforming activity. Holding plasmid DNA which had been treated with UV-A light in the presence of citral at 4 degrees C for 22 h in the dark resulted in continued degradation of the DNA and loss of transforming activity. Holding plasmid DNA treated with UV-A or citral alone under identical conditions had no detectable effect on either plasmid conformation or transforming activity. PMID- 1502267 TI - Atmospheric sun protection factor on clear days: its observed dependence on solar zenith angle and its relevance to the shadow rule for sun protection. AB - Global irradiances measured in seven 5-nm bands of UV-B at Rockville, MD (39.1 degrees N, 77.1 degrees W) on 28 clear days near the summer solstice are convoluted with the erythemal action spectrum of human skin to determine dose rates at various hours of the day. These rates are averaged with respect to solar zenith angle to obtain the diurnal variation of mean dose rate and of the Sun Protection Factor (SPF) of the atmosphere (reciprocal of the normalized atmospheric transmissivity) on a typical clear summer day in Rockville. At a 45 degrees zenith angle the atmospheric SPF is computed to be 2.7 and increases rapidly to greater than 7 at 60 degrees. Dose rates are integrated with respect to time to obtain estimates of mean doses for various periods during clear days at Rockville in mid summer and near the autumnal equinox. In mid summer the effective erythemal UV-B exposure during the period when the solar zenith angle is less than 45 degrees is about five times greater than that during the remainder of the day. These observations provide scientific basis for a shadow rule for solar UV-B protection: when shadows are shorter than objects casting them, sunburn is much more likely than at other times. PMID- 1502266 TI - In vitro and in vivo ultraviolet-induced alterations of oxy- and deoxyhemoglobin. AB - Ultraviolet (UV) radiation was found to convert oxyhemoglobin and deoxyhemoglobin stoichiometrically into methemoglobin and a met-like product, respectively. The peak conversion efficiency for oxyhemoglobin occurred at 285 nm and decreased by a factor of 100 by 315 nm. The peak conversion efficiency for deoxyhemoglobin occurred at 290 nm and decreased by a factor of 30 by 320 nm. The transformation of oxyhemoglobin to methemoglobin was also documented in intact erythrocytes using UV-B radiation. Finally, similar transformations were found to occur in human skin with UV-B exposure but not on all volunteers tested. These results imply that methemoglobin will be formed in vivo on solar exposure and provide evidence that UV-B photons reach the blood vessels. PMID- 1502268 TI - Interphotoreceptor retinoid-binding protein and alpha-tocopherol preserve the isomeric and oxidation state of retinol. AB - Retinol decomposes rapidly into a number of products, including its aldehyde form, retinal, when introduced into buffer in phospholipid vesicles or ethanol. Interphotoreceptor retinoid-binding protein at low concentrations is found to protect retinol from isomerization and oxidation. The addition of alpha tocopherol to either liposomes or an ethanolic-buffer solution also prevents decomposition. Neither of these agents interferes with the successful regeneration of pigment with 9-cis retinal in rod outer segment preparations or the restoration of sensitivity by retinoids in isolated rod photoreceptors. PMID- 1502269 TI - Analysis of photo-oxidized amino acids in tryptic peptides of calf lens gamma-II crystallin. AB - Insoluble and crosslinked proteins and increased pigmentation in the eye lens are features of aging and cataracts. Determining the amino acids which are involved in insolubilization, crosslinking and visible light scattering will shed light on the mechanisms by which cataracts form. Calf lens gamma-II crystallin was irradiated at 295 nm, digested and separated into tryptic peptides. Additional tryptic peptides were found in the digest of irradiated gamma-II which were not present in the dark control digest. These peptides were identified by amino acid sequencing and shown to correspond to expected tryptic fragments of the protein, indicating more facile digestion in the UV-irradiated protein than in dark controls. Amino acid analysis of the irradiated protein and peptides showed losses of histidine, methionine and cysteine residues as compared to control samples. Tryptophan, which is not detected by amino acid analysis, was also found to be reactive since losses in its fluorescence intensity were observed after irradiation. Some of the photochemically active amino acids had lower than expected responses in amino acid sequencing experiments. This suggested specific sites of photochemical activity in the various peptides. The evidence for peptide crosslinks is also discussed. PMID- 1502270 TI - Photooxidation products of merocyanine 540 formed under preactivation conditions for tumor therapy. AB - In order to gain insight into the preactivation of merocyanine 540 (MC540) 1 for the photodynamic therapy (Gulliya et al., 1990a, Photochem. Photobiol. 52, 831 838) its photo-oxidation was investigated. After irradiation of MC540 1 on a preparative scale three main photodegradation products were isolated with 16-20% yields. They turned out to be derivatives of benzoxazole, thiouracil and thiohydantoin with the structures 4, 5 and 6, respectively. It may be possible that they contribute to the cytostatic and antiviral activity of preactivated MC540 1. PMID- 1502271 TI - Limited cell-cycle dependence of the merocyanine 540-sensitized photoinactivation of L1210 leukemia cells. AB - L1210 leukemia cells were synchronized by a double thymidine block technique and then characterized with regard to their susceptibility to merocyanine 540 (MC540) sensitized photoinactivation. Cells harvested 5 (G2/M phase) h after release from the second thymidine block were most susceptible to MC540-sensitized photoinactivation followed, in order of decreasing sensitivity, by cells harvested 2 (S phase) h and by cells harvested 7 (G1 phase) h after release from the second block. The expression of dye-binding sites changed very little during the cell cycle. PMID- 1502272 TI - Stagewise cognitive development: an application of catastrophe theory. AB - In this article an overview is given of traditional methodological approaches to stagewise cognitive developmental research. These approaches are evaluated and integrated on the basis of catastrophe theory. In particular, catastrophe theory specifies a set of common criteria for testing the discontinuity hypothesis proposed by Piaget. Separate criteria correspond to distinct methods used in cognitive developmental research. Such criteria are, for instance, the detection of spurts in development, bimodality of test scores, and increased variability of responses during transitional periods. When a genuine stage transition is present, these criteria are expected to be satisfied. A revised catastrophe model accommodating these criteria is proposed for the stage transition in cognitive development from the preoperational to the concrete operational stage. PMID- 1502273 TI - Inference during reading. AB - Most current theories of text processing assume a constructionist view of inference processing. In this article, an alternative view is proposed, labeled the minimalist hypothesis. According to this hypothesis, the only inferences that are encoded automatically during reading are those that are based on easily available information, either from explicit statements in the text or from general knowledge, and those that are required to make statements in the text locally coherent. The minimalist hypothesis is shown to be supported by previous research and by the results of several new experiments. It is also argued that automatically encoded minimalist inferences provide the basic representation of textual information from which more goal-directed, purposeful inferences are constructed. PMID- 1502274 TI - Dynamic binding in a neural network for shape recognition. AB - Given a single view of an object, humans can readily recognize that object from other views that preserve the parts in the original view. Empirical evidence suggests that this capacity reflects the activation of a viewpoint-invariant structural description specifying the object's parts and the relations among them. This article presents a neural network that generates such a description. Structural description is made possible through a solution to the dynamic binding problem: Temporary conjunctions of attributes (parts and relations) are represented by synchronized oscillatory activity among independent units representing those attributes. Specifically, the model uses synchrony (a) to parse images into their constituent parts, (b) to bind together the attributes of a part, and (c) to bind the relations to the parts to which they apply. Because it conjoins independent units temporarily, dynamic binding allows tremendous economy of representation and permits the representation to reflect the attribute structure of the shapes represented. PMID- 1502275 TI - Testing global memory models using ROC curves. AB - Global memory models are evaluated by using data from recognition memory experiments. For recognition, each of the models gives a value of familiarity as the output from matching a test item against memory. The experiments provide ROC (receiver operating characteristic) curves that give information about the standard deviations of familiarity values for old and new test items in the models. The experimental results are consistent with normal distributions of familiarity (a prediction of the models). However, the results also show that the new-item familiarity standard deviation is about 0.8 that of the old-item familiarity standard deviation and independent of the strength of the old items (under the assumption of normality). The models are inconsistent with these results because they predict either nearly equal old and new standard deviations or increasing values of old standard deviation with strength. Thus, the data provide the basis for revision of current models or development of new models. PMID- 1502276 TI - A critical role for "affective neuroscience" in resolving what is basic about basic emotions. AB - Ortony and Turner (1990) asked "What's Basic About Basic Emotions," and they concluded "very little." They proceeded to advocate a "componential" or "mosaic" view of how emotional systems should be analyzed. Their thesis was flawed by their failure to consider the available neurobehavioral data. Genetically dictated brain systems that mediate affective-emotional processes do exist, even though there are bound to be semantic ambiguities in how we speak about these systems. This commentary summarizes key lines of evidence for coherently operating emotional systems in the brain and advocates the position that the issue of basic emotions can no longer be credibly discussed without adequate consideration of the relevant brain research in the area. The type of conceptual, logical analysis pursued by Ortony and Turner, in the absence of a thorough analysis of the available neurological data, is not an adequate basis for resolving what is basic about basic emotions. PMID- 1502277 TI - Basic emotions, relations among emotions, and emotion-cognition relations. AB - From the cognitive theory perspective that emotions are cognition dependent and contain cognitive components, Ortony and Turner (1990) questioned the validity of the concept of basic emotions. They argued that the so-called basic emotions were neither psychologically or biologically "primitive" nor "irreducible building blocks" for generating the "great variety of emotional experiences." In the biosocial theory tradition, researchers have identified multiple noncognitive activators of emotion and demonstrated the usefulness of defining the essential components of emotion as phenomena that do not require cognitive mediators or constituents. In this framework, emotions are seen as basic because their biological and social functions are essential in evolution and adaptation. Particular emotions are called basic because they are assumed to have innate neural substrates, innate and universal expressions, and unique feeling motivational states. The great variety of emotional experiences is explained as a function of emotion-cognition interactions that result in affective-cognitive structures. PMID- 1502278 TI - Basic emotions: can conflicting criteria converge? AB - The authors discuss some of the key points raised by Ekman (1992), Izard (1992), and Panksepp (1992) in their critiques of Ortony and Turner's (1990) suggestion that there are and probably can be no objective and generally acceptable criteria for what is to count as a basic emotion. A number of studies are discussed that are relevant to the authors' contention that a more promising approach to understanding the huge diversity among emotions is to think in terms of emotions being assemblages of basic components rather than combinations of other basic emotions. The authors stress that their position does not deny that emotions are based on "hardwired" biological systems. On the other hand, the existence of such systems does not mean that some emotions (such as those that appear on lists of basic emotions) have a special status. Finally, the authors note that Ekman, Izard, and Panksepp, in adopting different starting points for their research, arrive at rather different conclusions as to what basic emotions are and which emotions are basic. It is concluded that converging resolutions of these questions are improbable. PMID- 1502279 TI - Categorization and metaphor understanding. AB - Glucksberg and Keysar (1990) have proposed a class-inclusion model of metaphor comprehension. This theory suggests that metaphors are not understood as implicit similes but are seen as class-inclusion statements in which the topic of a metaphor is assigned to a diagnostic, ad hoc category, whereas the metaphor's vehicle is a prototypical member of that category. The author claims that verbal metaphors are not simply instantiations of temporary, ad hoc categories but reflect preexisting conceptual mappings in long-term memory that are metaphorically structured. Various evidence from cognitive linguistics, philosophy, and psychology are described in support of this claim. Evidence is also presented that supports, contrary to Glucksberg and Keysar's position, the role of tacit conceptual metaphors in the comprehension of verbal metaphors in discourse. PMID- 1502280 TI - Society for Psychophysiological Research. 32nd annual meeting. San Diego, California, October 14-18, 1992. Abstracts. PMID- 1502281 TI - The whole patient is not less than the sum of his parts. PMID- 1502283 TI - Major depression in coronary artery disease patients with vs. without a prior history of depression. AB - Major depression (MD) is common in patients with coronary artery disease (CAD). Some of these patients have a history of prior depressive episodes, whereas others experience their first episode around the same time that their CAD is diagnosed. The purpose of this study was to determine whether there are systematic differences between these two subgroups of depressed patients. Of 39 patients with recently diagnosed CAD who met DSM-III-R criteria for MD, 17 (44%) had a prior history of MD. This subgroup had a higher proportion of females (p less than 0.003), more severe depression (p less than 0.004), were marginally younger (p = 0.08), and had slightly less severe CAD (p = 0.07) compared with those with no prior history of MD. These results support the hypothesis that there may be two distinctive subtypes of MD in patients with CAD. Additional studies are needed to determine whether these subgroups differ with respect to course, treatment, and relationship to the coronary artery disease. PMID- 1502282 TI - Effects of experimental psychological stress on distribution and function of peripheral blood cells. AB - Fifty male subjects (aged 24 to 55 years) were subjected to a mild and potentially uncontrollable interpersonal stress situation. They were asked to solve a difficult puzzle. Subsequently they were requested to explain their solution to "another subject," actually a confederate to the researchers. The confederate frustrated the subjects' explanation efforts. Care was taken that neither solving nor explaining of the puzzle was successful. The experimental situation induced mild psychological strain as documented by mood changes in the experimental group when compared with a control group of 36 male subjects. Peripheral blood was drawn by an indwelling catheter just before, directly after, 15 minutes after, and 30 minutes after the stress situation. Numbers of leukocytes, lymphocytes, monocytes, T-cell subsets, natural killer (NK) cells, and B-cells were determined. As functional assays we used in vitro proliferative responses of T- and B-cells to mitogenic stimulation (PHA and PWM) and to an antigen cocktail. The potential influences of health- and biobehavioral variables were taken into account in the analyses, as well as incidental differences in initial mood or immunological baseline. The results replicated and expanded on previous research. In contrast to controls, experimental subjects showed a significant increase in numbers of NK cells after the stress-period, returning to baseline values after 15 minutes of rest. A similar effect was shown on T suppressor/cytotoxic cells and, inversely, on T-helper/suppressor ratio, but these effects could be attributed to changes in the numbers of CD8+CD57+ cells. No effects were observed on proliferation. From the results we conclude that the effects of a short lasting mild psychological stressor are mainly restricted to cells of the NK cell population. PMID- 1502284 TI - Cardiovascular differentiation of emotions. AB - This study examined the cardiovascular mechanisms governing differential blood pressure changes during the emotions of joy, sadness, fear, and anger. Heart rate, blood pressure, stroke volume, peripheral vascular resistance, cardiac output, and indices of myocardial contractility were measured during fear, anger, joy, sadness, physical action, and neutral imagery conditions in 27 right-handed male volunteers screened for imagery ability, alexithymia, anxiety, and depression. Anger imagery, rather than fear, was accompanied by the largest effects on the cardiovascular system. Increased diastolic blood pressure in anger was associated with maintained levels of peripheral vascular resistance and increased cardiac output and heart rate compared with changes during neutral imagery. Sadness produced a distinct pattern with moderate increases in blood pressure and vascular resistance and a decrease in cardiac output compared with changes during neutral imagery. Fear, action, and joy produced similar blood pressure changes in which systolic pressure increased and diastolic pressure was relatively unchanged. The measurement of cardiac output and determination of vascular resistance changes during emotional imagery demonstrate that previously observed emotion-specific blood pressure responses are produced by underlying patterns of cardiovascular activation, which differ between the major categories of emotions. PMID- 1502285 TI - Diminished pulse pressure response to psychological stress: early precursor of essential hypertension? AB - An excessive blood pressure response to mental stress is a widely reported characteristic of young normotensive offspring of hypertensive parents. At odds with these reports are data from a large biracial study showing that high risk adolescent offspring had diminished pulse pressure under mental stress and no evidence of greater blood pressure reactivity. We examined this apparent contradiction in a similar but larger sample of 213 normotensive adolescents, comparing blood pressure and heart rate responses to video game, mirror drawing, mental arithmetic, interview, and physical exercise in high- and low-risk offspring. Results replicated the diminished pulse pressure finding, suggesting it is characteristic of African Americans and is evoked by behavioral tasks that entail skeletal-motor inhibition. Submaximal physical exercise failed to discriminate between offspring groups. Possible biologic correlates of diminished pulse pressure in black adolescents with "high normal" blood pressure warrant further investigation. PMID- 1502286 TI - Behavioral clusters and coronary heart disease risk. AB - The purpose of the present study was to empirically identify individuals who differed in their patterns of components derived from the structured interview (SI), and to evaluate whether individuals characterized by the different patterns varied in terms of their risk for coronary heart disease (CHD). The present study represents a reanalysis of data from the Western Collaborative Group Study in which components of Type A were individually related to risk for CHD. Subgroups of individuals who differed in the patterns of their component scores were identified by means of cluster analytic techniques and were found to vary in their risk of CHD. As expected, a pattern of characteristics in which hostility was salient was found to be predictive of CHD. Moreover, another pattern of characteristics that appears to reflect pressured, controlling, socially dominant behavior in which hostility was not salient also was found to be predictive of CHD. Further, two patterns of characteristics were identified that were unrelated to CHD risk. Finally, two patterns of characteristics were identified that were related to reduced risk of CHD. Overall, these results suggest that future research should investigate variables in addition to hostility in regard to risk for and protection from CHD. PMID- 1502287 TI - Power spectral analysis of heart rate variability in Type As and Type Bs during mental workload. AB - Recently several studies have suggested that there are differences in autonomic balance between Type As and Type Bs. This study evaluates a sympathovagal interaction in Type A (n = 8) and Type B (n = 11) male students during a mental arithmetic task by power spectral analysis of heart rate variability. The low frequency component to high-frequency component ratio was significantly greater in Type As than in Type Bs during a resting period. No significant differences were found in heart rate changes and blood pressure between the two kinds of subject groups. The present findings indicate that there was a significant difference in sympathovagal balance between Type As and Bs. Type As showed dominant sympathetic activity. PMID- 1502288 TI - Family stress and coronary risk in children. AB - This study examined children of 64 families for associations between a) family conflict and cohesion and b) plasma lipids, lipoproteins, and aggressiveness. Ratings of conflict and cohesion were obtained from parents. Children rated themselves on aggressiveness, one component of Type A behavior. The presence of conflict in the family was positively related to an unfavorable lipid profile (total plasma cholesterol/high-density lipoprotein cholesterol) among boys, but not girls. Family conflict predicted increased levels of aggression in girls, and in boys whose family cohesion was low. These findings suggest that stress in the family may play an important role in the development of coronary risk. PMID- 1502289 TI - "Person under train" incidents: medical consequences for subway drivers. AB - From the subway driver's point of view, a "person under train" (PUT) incident is a serious life event. This study focuses on the 1-year consequences of such events. Follow-up was made 3 weeks, 3 months, and 1 year after the event. Forty consecutive PUT subway drivers were followed. For each PUT driver, a control driver matched with regard to gender, age, and country of birth was followed at identical intervals. MAIN RESULTS: The PUT group had significantly more sick days during the interval from the event to 3 weeks later. During the period 3 weeks to 3 months after the event no difference between the groups was observed. From 3 months to 1 year after the PUT significantly more days were again reported by the PUT group. Thirty-eight percent in the PUT group versus 14% in the control group had at least 1 month of sickness absence during this period. A mild acute psychophysiological reaction was observed 3 weeks after the event, with elevated prolactin and increased sleep disturbance in the PUT group. Such acute reactions were transitory and not correlated with long-term sick leave, which was predicted independently, however, by a high plasma cortisol level (analyzed in men) and a high depression score. Drivers in the group with seriously injured victims were absent from work for longer periods than drivers in the groups with mildly injured or dead victims. PMID- 1502290 TI - Effects of psychological treatment on cancer patients: a critical review. AB - Twenty-two studies on the effects of psychological treatment on cancer patients are reviewed. Only studies that compared one or more experimental conditions with at least one control group have been considered. The studies were evaluated with respect to a) research methods, b) psychological interventions, and c) results. Tailored counseling has been shown to be effective with respect to distress, self concept, (health) locus of control, fatigue, and sexual problems. Structured counseling showed positive effects with respect to depression and distress. Behavioral interventions and hypnosis were effective with respect to specific symptoms such as anxiety, pain, nausea, and vomiting. The research methods, interventions and results of the studies are reviewed critically. Several recommendations for future research are made. PMID- 1502291 TI - Cognitive processing of contradictory statements: an experimental study of reasoning on proverbs in schizophrenia. AB - Twenty schizophrenic patients and 20 normal subjects matched for age, sex and verbal level were asked to identify, from a list of alternatives, the statement that was the most contradictory to each of 8 proverbs. Schizophrenics (whether severely disturbed or not) were found to be less accurate in detecting the contradictions [F(1,18) = 29.21; p less than 0.0001]. No significant differences between undifferentiated and disorganized DSM-III subtypes were observed. The greatest tolerance of contradictory statements was interpreted in terms of violation of the 'no contradiction principle' and examined in the light of a deficit in logical abilities. PMID- 1502292 TI - Psychomotor activity in unipolar and bipolar depressive patients. AB - Findings on the psychomotor activity of unipolar versus bipolar depressive patients and on the relationship between psychomotor activity and sleep are divergent. In this study, the psychomotor activity of 37 depressive patients (25 unipolar, 12 bipolar) was examined by means of continuous actometric monitoring (48 h). The mean activity level of the unipolar depressives is higher (though not at a significant level) than that of the bipolar group. There is a weak but significant negative correlation between psychomotor activity and self-rated sleep time. Elderly and female patients display greater psychomotor activity than younger depressives and male patients. After matching for age and gender, the psychomotor activity of unipolar and bipolar patients is virtually identical; a significant correlation between psychomotor activity and sleep time cannot be established any more. PMID- 1502293 TI - Deficit of birthrates in winter and spring months in distinct subgroups of mainly genetically determined schizophrenia. AB - The birthrates of 507 schizophrenic patients with high familial loading were compared to the general population. The patient group showed a clearcut decrease in births within a defined winter and spring period. In particular, this was obvious if Leonhard's classification of schizophrenia was applied. The hypothesis is proposed that, in some fetuses at high genetic risk for schizophrenia, an exaggerated level of abortions or stillbirths occurs if additional environmental noxious agents are present in a crucial period of brain maturation. Pertinent evidence in support of this is found in literature. PMID- 1502294 TI - Patterns of abnormal processing of emotional information in panic disorder and major depression. AB - Studies showing interference with color naming threat-related words in patients with anxiety disorders suggest a bias towards processing threatening material in these patients. We assessed the specificity of this finding to anxiety disorders and to threatening stimuli by administering Stroop cards with a variety of types of emotional stimuli to 24 panic disorder patients with no history of major depression, 30 patients with major depression and no history of panic attacks and 25 controls with no history of an axis I disorder. Our findings suggest that the abnormal information processing seen in panic disorder may be characterized by a more general bias towards processing emotional stimuli than previously thought. They also suggest that this more general bias may illustrate differences in information processing in panic disorder and major depression. PMID- 1502295 TI - On the descriptive validity of DSM III schizophrenia. AB - The study sample is drawn from patients seeking evaluation in a psychiatric intake facility. It concentrates on those who are assigned a diagnosis of psychosis as stipulated in DSM III. The aim is to elucidate the distinguishing characteristics of patients diagnosed as Schizophrenia Disorder. The descriptive validity of this disorder is pursued by systematically comparing clinical and demographic characteristics of patients with this disorder to those diagnosed as Paranoid Disorder, Atypical Psychosis, Brief Reactive Psychosis, Schizoaffective Disorder and Schizophreniform Disorder. These comparisons uncover special characteristics pertaining to the demography and impact of schizophrenia. The results obtained are explained using generalizations drawn from the epidemiology, natural history and clinical manifestations of schizophrenia and other psychoses. PMID- 1502296 TI - Sex differences and distinct subgroups in schizophrenia. A study of 54 chronic hospitalized schizophrenics. AB - Sex differences with regard to age at first hospitalization and residual symptomatology were investigated in 54 long-term hospitalized chronic schizophrenics. Patients fulfilled diagnostic criteria of DSM-III, Kraepelin's dementia praecox and Leonhard's group of schizophrenias as well. The severe residual psychopathology necessitated continuous hospitalization in all the patients. The 27 women and 27 men neither differed in duration of illness or period of hospitalization nor in their social environment. We found that women were older than men at their first hospitalization and exhibited more marked positive symptomatology during the course and in the residual state than men. However, regardless of the residual symptomatology, men generally received more neuroleptics. A classification of the schizophrenic patients by means of the Leonhard criteria revealed that unsystematic schizophrenics (affect-laden paraphrenia, periodic catatonia, cataphasia) of both sexes were significantly (p less than 0.001) more often married at the time of first hospitalization than were systematic schizophrenics. Further, there was an overwhelming preponderance of women among the group of affect-laden paraphrenia and, conversely, of men in the group of periodic catatonia. Presuming different etiology in affect-laden paraphrenia and periodic catatonia, our findings suggest a significantly varied frequency in the rate in which women and men are afflicted by heterogeneous subgroups of schizophrenia. PMID- 1502297 TI - Acid etching of dentin: too early to recommend. PMID- 1502298 TI - Composite resin veneers: a new technique. AB - A new technique for the fabrication of composite resin direct veneers is presented. In this technique, a transparent acrylic resin matrix is fabricated before preparation of the facial surface of the tooth, to allow the adequate reproduction of contour, shape, and surface texture originally exhibited by the tooth. Advantages, as well as limitations, of the procedure are also presented. PMID- 1502299 TI - The use of adhesive metal partial crowns to restore attrition defects: a case report. AB - A patient presented with severe loss of enamel on the palatal surface of the maxillary anterior teeth, resulting from attrition. After correction of the mandibular occlusal position, the palatal defects were restored with metal partial crowns cemented with an adhesive cement. One of the six restorations dislodged during 4 years of observation, but was replaced successfully. PMID- 1502300 TI - Treatment of gingival lichen planus with a free gingival graft: a case report. AB - Lichen planus is an inflammatory dermatosis affecting the skin and mucous membrane. In oral lichen planus, the gingival tissue is often involved. Treatment is symptomatic and depends mostly on the administration of corticosteroids and tranquilizers. This report presents the case of a patient with gingival lichen planus who was treated with free gingival graft. Followup after 3 1/2 years showed that the lesions had completely disappeared. PMID- 1502301 TI - A new technique for the custom fabrication of mouthguards with photopolymerized urethane diacrylate. AB - The use of protective mouthguards in athletes has proven to be an effective and inexpensive means of preventing traumatic injuries to the teeth and supporting structures. Of the three general types of mouthguards available currently, the custom-fabricated type is considered superior to stock and mouth-formed protectors. A new technique is introduced for the fabrication of custom-made mouthguards with light-curing urethane diacrylate material. PMID- 1502302 TI - Reparative dentin: factors affecting its deposition. AB - Results of this study showed no correlation between the thickness or amount of reparative dentin deposited and the type of dental restorative material placed at either 5 or 8 weeks in controlled Class V cavity preparations in monkey teeth. Factors such as preparation trauma from the bur, operator hand instrumentation, and microleakage of bacterial toxins played a greater role in the stimulation of reparative dentin than did material irritation or toxicity. Some differences in the thickness of the reparative dentin deposited were noted when teeth were grouped according to the amount of remaining dentin. PMID- 1502303 TI - In vitro evaluation of marginal fit and morphology of fired ceramic inlays. AB - The marginal adaptation of fired ceramic inlays prepared by three dental technicians in two ceramic materials was evaluated in vitro. The thickness of the sealing gap varied between 46.4 and 57.6 microns, and the percentage of marginal ceramic defects ranged between 8.6% and 25.0% of the total inlay circumference. The incidence of marginal defects increased in areas of complex occlusal morphology. Differences observed in inlay adaptation were related to the technician rather than to the material used. The accuracy of ceramic inlays was comparable to that of metallic and porcelain-fused-to-metal crowns with butt joint margins and fell within the range of clinically acceptable adaptation. PMID- 1502304 TI - In vitro corrosion behavior of 13 prosthodontic alloys. AB - The corrosion behavior of 12 high-gold, low-gold, palladium-silver, and nickel chromium alloys was tested using electrochemical techniques. A 22-carat-gold alloy was used as a control. High-gold alloys were extremely resistant to corrosion, but the resistance of the alloys decreased with decreasing mobility (from high-gold, to palladium-silver, to low-gold, to nickel-chromium alloys). Tests were also made to determine the type of corrosive attack; nickel-chromium alloys exhibited pitting, and palladium-silver alloys demonstrated the selective dissolution of the silver-rich phases. The corrosion resistance of noble alloys was far superior to that of nickel-chromium-based alloys; therefore, the palladium-silver alloys, which have a moderate price range, may be more suitable for restorations. PMID- 1502305 TI - Preventive resin restorations: indications, technique, and success. AB - Although preventive resin restorations have been reported since 1977, there is little uniformity concerning the indications for this procedure, nor is there a standard technique. This article proposes diagnostic criteria for pit and fissure occlusal caries and diagnosis-related considerations for treatment planning for preventive resin restorations. A step-by-step "laminate" technique, which includes, successively, a glass-ionomer cement liner, a posterior composite resin, and a sealant, is described. The success rates reported for several clinical studies of preventive resin restorations are presented, although the criteria for this restoration, treatment methodology, and the determinates of success vary from study to study. PMID- 1502306 TI - Enamel microabrasion followed by dental bleaching: case reports. AB - Certain enamel coloration defects can best be eliminated by a combination of treatment methods. This report describes the treatment of two patients whose enamel discoloration was corrected with a combination of enamel microabrasion and patient-administered dental bleaching with a carbamide peroxide gel solution. PMID- 1502307 TI - Treatment of Class II open bite in the mixed dentition with a removable functional appliance and headgear. AB - Early diagnosis of patients exhibiting open bites that are complicated by skeletal Class II and vertical growth problems can facilitate subsequent treatment. Eight patients with Class II skeletal open bite were treated with the high-pull activator appliance and compared to reasonably matched controls to determine the effects of the appliance. The high-pull activator was found to reduce forward growth of the maxilla and increase mandibular alveolar height, transforming the Class II molar relationship into a Class I molar relationship. The overjet and open bite were decreased, and, in addition, the appliance reduced the amount of forward and downward movement of the maxillary molars, providing vertical control of the maxilla during Class II orthopedic correction. These results demonstrated that open bite complicated by a Class II vertical growth pattern can be treated during the mixed dentition with favorable results by a combination of a removable functional appliance and high-pull headgear. PMID- 1502308 TI - In vitro growth of periodontal fibroblasts on treated cementum. AB - The aim of the present study was to assess the ability in vitro of phosphoric and citric acids, applied on human root cementum, to neutralize noxious plaque and calculus and to allow the growth of human gingival fibroblasts. Fibroblasts grown on cementum treated with phosphoric acid appeared typically elongated and aligned parallel to the root surface. Fibroblasts grown on cementum treated with citric acid, in both normal and periodontally diseased teeth, lost their elongated shape, acquiring polygonal borders with irregular cytoplasmic extrusions, and the cell density was significantly lower. These findings suggest that phosphoric acid cleaning of both normal and diseased root surfaces may result in an oriented, high rate of fibroblastic growth with more effective periodontal cellular proliferation than that observed after citric acid treatment. PMID- 1502309 TI - Tooth buildup prior to endodontic treatment. AB - Inadequate isolation will greatly compromise routine endodontic therapy. Loss of coronal tooth structure to caries or trauma often makes adequate rubber dam isolation difficult to achieve. This article presents some techniques for placing a buildup prior to endodontic therapy. The few minutes spent placing a buildup prior to the initiation of root canal therapy are an excellent investment in time. The time spent will be repaid by the ease of placement of the rubber dam, the quality of isolation achieved, the reduced chance of losing the provisional restoration, and the increased quality of the completed endodontic treatment. PMID- 1502310 TI - Bilateral transposition of maxillary canines and first premolars: case report. AB - Transposition of teeth is a rare phenomenon. A case of bilateral transposition of maxillary canines and first premolars in a 27-year-old man is described. PMID- 1502311 TI - Color vision and dentistry. AB - Color vision is a critical component of restorative and esthetic dentistry, but dentists, as a group, do not have their color vision tested at any time during their careers. A study was undertaken to ascertain the color-vision status of practicing dental personnel at the University of Tennessee, College of Dentistry. One hundred fifty individuals, 75 men and 75 women, were screened. The results corroborated the existing medical data for the general population. It was found that 9.3% of the men and none of the women exhibited color-vision defect. Since most dentists are male, this study demonstrates an area of potential weakness for some practitioners. Once a color-vision problem is found, it is simple to remedy by employing a team approach to shade matching or mechanical means of matching shades (by the practitioner). No ethnic or racial distinctions were detected, although these have been reported in other studies. PMID- 1502312 TI - In vitro evaluation of dentinal bonding agents in mixed Class V cavity preparations. AB - The effect of ten dentinal bonding agents on composite resin restorations was tested in mixed Class V cavity preparations. The marginal quality of the restorations was quantified under a scanning electron microscope before and after thermocycling. In addition, the marginal seal was semiquantitatively evaluated with a dye penetration technique. Marginal adaptation in dentin was poor in seven test groups. Three products showed values of excellent margin in dentin exceeding 50% after thermocycling. Furthermore, some dentinal bonding agents had a deleterious effect on marginal adaptation to the etched enamel surfaces. PMID- 1502313 TI - The prevalence of nonrepaired fractured incisors in visually impaired Chinese children and young adults in Hong Kong. AB - The purpose of this study was to determine the prevalence of nonrepaired fractured incisors in visually impaired Chinese children and young adults in Hong Kong. Eighty-eight children were examined, and it was found that there were significantly more fractures of anterior teeth in the totally blind than in the partially blind. The totally blind seem to be at greater risk of sustaining a fractured anterior tooth than were the sighted. PMID- 1502314 TI - The influence of environmental pressure on retentiveness of prosthetic crowns: an experimental study. AB - To determine the effect of pressure variations on the retention of prosthetic crowns, 36 identical, cast metal crowns were fixed to simulated, epoxy resin crown preparations with zinc oxyphosphate cement. Eighteen specimens were placed in a hyperbaric chamber and subjected to 15 cycles of simulated immersion at 30 m and decompression, as usually carried out by scuba divers. The untreated specimens served as controls. When the force required to dislodge the crowns was measured, the treated crowns were dislodged at about one third the load that was required to dislodge the control group, indicating that a statistically significant decrease in cement strength follows pressure variations. PMID- 1502315 TI - Zinc oxide-eugenol pulpotomy and stainless steel crown restoration of a primary molar. AB - The most durable and reliable method of retaining a primary molar in the mouth after a pulpotomy procedure is complete-coverage restoration with a preformed stainless steel crown. This paper describes a method for performing pulpotomy and stainless steel crown restoration of a primary molar. Neither formocresol, glutaraldehyde, nor calcium hydroxide is used during the pulpotomy phase of the treatment. PMID- 1502316 TI - Corrosion of a nonprecious metal post: a case report. AB - This paper describes a case in which an endodontically treated molar, which was restored with a post-retained cast restoration, was eventually lost following corrosion of the nonprecious metal post and fracture of the distal root. PMID- 1502317 TI - Orthodontic forced eruption: case report of an alternative treatment for subgingivally fractured young permanent incisors. AB - Subgingivally fractured incisors are still a challenge to treat. A case report is used as a basis for reviewing the different treatment options, which involve either extraction or preservation of the root. A multidisciplinary approach, using orthodontic forced eruption, is presented in detail. PMID- 1502318 TI - A guide for tooth resection with a used reamer or file. AB - Tooth resection is an important procedure, frequently encountered in dental treatment. A surgical guide is essential to providing the direction for tooth resection. A used (dulled) endodontic reamer or file can be utilized as directional guide for tooth resection, because it is economical, autoclavable, and safe. The clinical use of this surgical guide is described. PMID- 1502319 TI - Overdentures and the periodontium. AB - Several periodontal factors are critical to the prognosis of overdenture abutment teeth. This literature review outlines these factors and discusses the documented effects of long-term overdenture use on periodontal health. The efficacy of a professional periodontal maintenance program, which is coordinated with a home oral hygiene program, is related to the success of overdenture therapy. PMID- 1502320 TI - A new method for positioning the maxillary anterior arch, orienting the occlusal plane, and determining the vertical dimension of occlusion. AB - A new method for positioning the maxillary anterior arch, orienting the occlusal plane, and establishing the vertical dimension of occlusion in edentulous patients is described. The procedure uses a newly developed registration pin assembly that is fixed to the maxillary acrylic resin baseplate. The vertical dimension of occlusion is determined by having the patient swallow. This approach eliminates the tedious and time-consuming process of trimming the occlusion wax rims. The accuracy of the new method is currently being evaluated. PMID- 1502321 TI - Fabrication of a fixed provisional restoration utilizing a light-curing acrylic resin. AB - The properly fabricated provisional restoration must take into account the following interrelated factors: pulpal protection, periodontal health, occlusion, esthetics, and phonetics. The techniques advocated for construction of a provisional restoration include direct, indirect, and a combination of direct and indirect techniques. Two simple techniques that use light-curing acrylic resin for the fabrication of fixed provisional restorations are presented, and advantages and disadvantages of these techniques are discussed. PMID- 1502322 TI - Effect of bonded gold inlays on fracture resistance of teeth. AB - The purpose of this study was to determine if bonding gold inlays to tooth structure with an adhesive resin cement would increase the fracture resistance of restored teeth. Extracted paired maxillary premolars were prepared for mesio occlusodistal inlays, and the inlays were cast in type II gold. In one tooth of each pair, the inlay was sandblasted with aluminium oxide, tin plated, and cemented with an adhesive resin into the etched preparation. For the other (control) tooth in each pair, the inlay was sandblasted and then cemented into the preparation with zinc phosphate cement. The teeth were thermocycled and loaded until fracture. The teeth in the bonded group had a statistically significantly higher fracture resistance than did the teeth in the control group. Scanning electron microscopic examination revealed that failure in the bonded group occurred predominantly within the resin. PMID- 1502323 TI - Calcium release after acid pretreatment of fluoridated and nonfluoridated enamel. AB - Spectrophotometric analysis of calcium released by the acid-etching procedure was used to evaluate the effect of topical fluoride on the acid resistivity of enamel. The influence of superficial enamel surface reduction (chamfering) on the efficacy of the etching procedure was investigated. PMID- 1502324 TI - Comparative investigation of dynamic loading of prepared and intact human premolars. AB - The aim of this study was to obtain some data on the dynamic strength of premolar teeth. Experiments were performed on three groups of human premolars: intact teeth, teeth prepared for partial veneer crowns with flat occlusal surfaces, and teeth prepared for partial veneer crowns with rounded occlusal surfaces. The loading procedure was performed in a modified Amslers high-frequency pulsator. The greatest dynamic strength was exhibited by the intact specimens. The highest continual (unlimited number of loading cycles) dynamic stress withstood by all three groups of premolars was about 300 N. A statistically significant negative correlation was found between Fmax and the number of cycles in all three tested groups. PMID- 1502325 TI - A scanning electron microscopic observation of inner carious dentin after cleansing and of the dentin-resin interface. AB - Inner carious dentin after cleansing and the dentin-resin interface were observed with scanning electron microscopy. Results suggested that, similar to 10% citric acid-3% ferric chloride solution, 10% ethylenediaminetetraacetic acid may thoroughly remove the smear layer on the surface of inner carious dentin and make it possible for the dentinal bonding agent to penetrate the cleansed dentin to form an acid-proof layer and dense resin tags. These changes may improve the bond strength as well as tubule aperture seal. Ethylenediaminetetraacetic acid is not destructive to collagen, and may be of negligible toxicity to the pulp of intact dentin. PMID- 1502326 TI - LET, track structure and models. A review. AB - Swift heavy ions when penetrating through matter strip off those electrons having a smaller orbital velocity than the ion velocity. The remaining electrons screen the nuclear charge yielding an effective charge. The effective charge of the ions interacts predominantly with the target electrons causing excitation and ionizations of the target atoms. Using the Bethe Bloch formula for the energy loss combined with the Barkas formula for effective charge, the energy loss values as well as unrestricted and restricted linear transfer can be calculated within a few percent of accuracy. From the primary energy loss only a small fraction of 10% or less is transformed into excitation. The major part of the energy loss is used for the ionization of the target atoms and the emission of the corresponding electrons with a high kinetic energy. These electrons form the track around the trajectory of the primary ion in which two thirds of the primary energy is deposited by collisions of primary, secondary and later generations of electrons with the target molecules. In the electron diffusion process the energy is transported from the center of the track into the halo. The radial dose decreases with the square of the radial distance from the center. The diameter of the track is determined by the maximum range of the emitted electrons, i.e. by the maximum energy electrons. All ions having the same velocity i.e. the same specific energy produce electrons of the same energy and therefore tracks of the same diameters independent of the effective charge. But the dose inside the track increases with the square of the effective charge. Track structure models using this continuous dose distributions produce a better agreement with the experiment than models based on microdosimetry. The critical volume as used in microdosimetry is too large compared to the size of the DNA as critical structure inside the biological objects. Track structure models yield better results because the gross-structure of the track i.e. its lateral extension and the thin down toward the end of the track is included in these calculations. In a recent refinement the repair capacity of the cell has been included in a track structure model by using the complete shouldered x-ray survival curve as a template for the local damage produced by the particle tracks. This improved model yields presently the best agreement with the experiment. PMID- 1502327 TI - Cell inactivation by heavy charged particles. AB - The inactivation of cells resulting in lethal or aberrant effects by charged particles is of growing interest. Charged particles at extremely high LET are capable of completely eliminating cell-type and cell-line differences in repair capacity. It is still not clear however whether the repair systems are inactivated, or merely that heavy-ion lesions are less repairable. Studies correlating the particle inactivation dose of radioresistant cells with intact DNA analyzed with pulse field gel electrophoresis and other techniques may be useful, but more experiments are also needed to assess the fidelity of repair. For particle irradiations between 40-100 keV/microns there is however evidence for particle-induced activation of specific genes in mammalian cells, and certain repair processes in bacteria. New data are available on the inactivation of developmental processes in several systems including seeds, and cells of the nematode C. elegans. Future experimental and theoretical modeling research emphasis should focus on exploring particle-induced inactivation of endpoints assessing functionality and not just lethality, and on analyzing molecular damage and genetic effects arising in damaged but non-inactivated survivors. The discrete nature of selective types of particle damage as a function of radiation quality indicates the value of accelerated ions as probes of normal and aberrant biological processes. Information obtained from molecular analyses of damage and repair must however be integrated into the context of cellular and tissue functions of the organism. PMID- 1502328 TI - Radiobiological problems in space. An overview. PMID- 1502329 TI - Light ion accelerators for cancer therapy. AB - The paper concentrates on the accelerator choices for light ion cancer irradiation facilities, as outlined in several proposals over the last 15 years and concludes with the description of a modern synchrotron facility. Further summary papers on the same subject are cited in references [14, 19]. PMID- 1502330 TI - Beam delivery systems for charged particles. AB - Heavy charged particle therapy, started at research institutes three decades ago, is now on the verge of entering a clinical phase. This phase has resulted from the evolution and development of various beam delivery systems and techniques with existing research accelerators and with newly built accelerators. For the first thirty years, heavy charged particle therapy was administered with a fixed horizontal beam line. In 1991, the first treatment with an isocentric gantry was administered. The development of the isocentric gantry, the newest beam delivery system, and clearly a consequence of all the experience gained at the earlier facilities has many advantages. It offers advantageous physical properties of the particles as well as being equal in the flexibility of dose delivery to the modern photon radiotherapy gantries. PMID- 1502331 TI - Clinical gain from improved beam delivery systems. AB - The feasibility of dynamic conformal heavy charged particle radiotherapy has been investigated at UCLBL, and shows high promise of: 1. an improved therapeutic ratio and 2. reduction in the number of treatment portals required for efficient treatment delivery. Assessment of dose to tumor and critical structures for several anatomical sites have been carried out using a normal tissue complication algorithm developed at LBL. For high-LET charged particle treatment delivery, dynamic conformal therapy using a raster scanned beam with variable modulation and multileaf collimator appears to be the optimal technique for treatment delivery. PMID- 1502332 TI - 3D treatment planning for heavy charged particles. AB - The comments herein describe, at a necessarily superficial level, a number of issues which must be addressed in developing plans for heavy charged particle therapy. Programs now exist which provide the needed capabilities. The challenge now is to make the planning process easier and faster--and possibly more effective. It seems likely that this will be achieved in the next few years. PMID- 1502333 TI - Uses of 3D planning in addition to creating a good treatment: ongoing studies at MGH/HCL. PMID- 1502334 TI - Dose calculation and optimization for 3D conformal voxel scanning. PMID- 1502335 TI - The role of mesencephalic and thalamic arousal systems in experimental seizures. PMID- 1502336 TI - Central nervous angiotensin II responsiveness in birds. PMID- 1502337 TI - G protein activation of cardiac muscarinic K+ channels. PMID- 1502338 TI - Dopamine functions in appetitive and defensive behaviours. AB - The data reviewed here are compatible with the hypothesis that telencephalic dopamine activity is elicited by motivationally significant stimuli which in turn creates a neural state in which animals are more prepared to respond to significant stimuli in the environment. This analysis may be viewed as extensions of both the sensorimotor hypothesis, which depicts dopamine as potentiating the ability of stimuli to elicit responses (Clody and Carlton, 1980; Marshall et al., 1974; White, 1986) and of the incentive motivational hypothesis, which emphasizes the importance of dopamine in responding to stimuli that serve as signals of biologically significant events (Blackburn et al., 1989a; Crow, 1973; Mogenson and Phillips, 1976). In addition, we have sought to emphasize that not all responses are equally dependent upon the integrity of forebrain dopamine activity. Some responses, such as ingestion of standard foods by hungry animals, copulation, and escape, are relatively impervious to dopamine disruption. Further, once other behaviours, such as avoidance or appetitive operant responses, have been acquired, they can be maintained at an initially high rate despite perturbation of dopamine systems, although performance deteriorates with repeated testing. This analysis has emerged from the joint consideration of how both appetitive and defensive behaviours are influenced by dopamine antagonists, along with an examination of dopamine release during sequences of behaviour. The data reviewed suggest that dopamine is involved in fundamental psychological processes through which environmental stimuli come to exert control over certain aspects of behaviour. In the future, as knowledge in this field advances, there will have to be an integration of the literature on dopamine and motivation with the literature on dopamine and motor systems. We expect that dopamine release will be seen as a mechanism by which important environmental cues, of innate or learned significance, lead to a general enhancement of motor skeletal responses directed towards distal cues. We conclude with a caveat: Caution must be exercised when attempting to infer a general role of any neurotransmitter in motivated behaviour based on the study of a limited number of motivational systems. Although neurotransmitter pathways may figure prominently in the control of certain behaviours, it is incorrect to think of neurotransmitters as having a single role in behaviour. However, when comparative analyses reveal a common thread among different motivational systems, as is becoming apparent for the general role of mesotelencephalic dopamine pathways in behaviour, then the goal of generating coherent and comprehensive theory concerning a neurotransmitter's function in behaviour will begin to be realised.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1502339 TI - Thyroid receptors in the rat brain. PMID- 1502340 TI - Plasticity of the barrel cortex neurons. PMID- 1502341 TI - Peptides in cerebellar circuits. PMID- 1502342 TI - [Hypothesis of carcinogenesis by adaptive transformation in wound healing milieu]. PMID- 1502343 TI - [Structure and function of sequence directed DNA curvature]. PMID- 1502344 TI - [Structure and function of renal dipeptidase]. PMID- 1502345 TI - [Radiology as a profession: responsibility and risk]. PMID- 1502346 TI - [Chronic bronchiolitis in adults]. PMID- 1502347 TI - [Magnetic resonance in trigeminal neuralgia]. AB - One of the possible causes of the so-called "essential" trigeminal neuralgia is a neurovascular compression of the fifth cranial nerve root at the pons. The demonstration of this hypothesis could orientate the surgical treatment to microvascular decompression. In order to evaluate the role of MRI in the diagnosis of trigeminal neuralgia due to neurovascular compression, the authors present the results of a prospective evaluation of the cranial MR studies of 18 neuralgic patients in comparison with a retrospective evaluation of the cranial MR studies of 50 healthy control subjects. The results show that neurovascular compression can be demonstrated in 83.3% of the neurological patients. In all cases a good correlation between the clinical symptoms, the side of positive MR findings and the surgical findings, when available, was demonstrated. On the other hand, neurovascular compression was demonstrated in 28% of the healthy control subjects. The authors conclude that neurovascular compression can be demonstrated in a high percentage of patients with the so-called "essential" trigeminal neuralgia. Compared with the other imaging modalities (angiography, Computed Tomography) MRI is the best technique in the diagnosis of this disease. In fact, MRI is not only able to differentiate the symptomatic from the essential type of neuralgia, but is also very sensitive in the identification of trigeminal neuralgia due to neurovascular compression. This diagnosis could direct the surgical treatment to microvascular decompression. PMID- 1502348 TI - [Magnetic resonance in the study of the facial nerve: methodological approach and normal anatomy]. AB - The authors report their experience in the study of facial nerve anatomy by means of MR Imaging. The seventh pair of cranial nerves was studied in 6 healthy and informed volunteers with a super-conductive MR unit at 0.5 T using surface and head coils. Slices were 3 mm thick and were acquired on the axial and sagittal planes, when the petrous and the mastoid bones were studied. The parotid gland was studied with 5-mm slices acquired on the axial, angled axial, and sagittal planes. In all cases T1-weighted images (TR 450, TE 30) were performed. If the above research protocol, which is relatively simple and direct, is applied, the whole course of the facial nerve up to its main distal branches can be almost completely demonstrated. PMID- 1502349 TI - [Technical principles of solid tridimensional modeling with computerized tomography for the study of maxillofacial diseases]. AB - 3DCT allows the solid modeling of body structures from contiguous slices. The 3D images are free to rotate on the x, y, and z axes. It is possible to evidentiate structures with various densities by means of threshold operators, which allow a 3D model of both soft tissues and bones to be obtained. Shading operations allow image quality to be improved by varying the elementary units to surface units ratio. Implemented 3D rendering reduces the spatial edges by means of anti aliasing functions. The 3D images allow the study of the complexity of maxillofacial bony structures, and they are especially useful in both surgical planning and in postoperative follow-up. We studied 58 patients with maxillofacial diseases (34 traumatic, 14 malformations, 4 dysplastic, and 6 neoplastic). In most cases (96.5%), we obtained high-quality images, which allowed both the site and the extension of the lesions to be evaluated, together with their relationships to adjacent structures. In 65% of traumatic cases, the 4 basic views thoroughly demonstrated lesion spread, while in the extant 35% of cases cutting operations and rotatory translations were necessary. In all malformation cases a clear visualization of somatic asymmetries was obtained. In both dysplastic and neoplastic cases, the best lesion evidence was obtained in superficial lesions with cortical bone involvement. This technique was always easy and quick to perform, with no need for supplemental dose exposure to the patient. PMID- 1502350 TI - [Diffuse idiopathic skeletal hyperostosis. Review of diagnostic criteria and analysis of 915 cases]. AB - DISH is a common systemic skeletal disease, probably of dysmetabolic and/or degenerative origin, yet of unknown etiology. It is observed in middle-aged or elderly patients of both sexes, and is characterized by ossification of the anterior longitudinal ligament on the antero-lateral aspect of the spine, and by ossifying enthesopathy, in both the central and the peripheral skeleton. Diagnosis is solely based on radiographic abnormalities, according to the so called Resnick criteria. In the present study, the spines of 915 patients (414 males, 501 females, mean age: 65 years) were considered, and the peripheral entheses (heel, patella and elbow) of 494 of them (234 males and 260 females). The incidence of DISH was 14.09% (129 cases): 17.6% in males (73 cases) and 11.7% in females (56 cases). DISH strikes in the VI and VII decades of life most. The most affected sites of the spine were: the dorsal portion (100%), especially in the D7-D11 segment (93%); the lumbar spine in L1-L3 (81%), and the cervical spine, in the C5-C7 segment (69%). Peripheral areas of involvement were: pelvis (90%), heel (76%), elbow (46%) and knee (29%). The symptoms of DISH must be promptly detected: the disease is not asymptomatic, but presents with pain and stiffness in the spine, recurrent tendinitis and bursitis, and myelopathy. PMID- 1502351 TI - [Ultrasonic assessment of the capsular-ligamentous structures of the ankle. Normal features]. AB - The study of normal ankles by means of US has enabled the authors to define the articular system so as to obtain a useful reference for the study of pathological ankles. A real-time (Ansaldo AU 530) unit with a 10 MHz sectorial probe was employed together with a Toshiba unit with a 7.5 MHz sectorial probe. In 6 cases, the stretching of the capsuloligamentous system before arthroscopy was examined. The authors' attention focused on 3 major functional anatomic areas: the talofibular ligament area, the calcaneofibular ligament area, and the deltoid ligament area. The comparison of US scans before and after stretching the capsula with a physiological solution allowed the most interesting structures to be recognized and quantified from a US-anatomical point of view. Useful parameters were both the length of the lateral aspect of the ligament (mean difference in length between rest and exercise conditions: 15 mm for the anterior talofibular ligament and 14 mm for calcaneofibular ligament) and the thickness of intra articular echoes (mean value: 5 mm). PMID- 1502352 TI - [Mammography and echography in the study of breast prosthesis]. AB - Between October 1990 and December 1991, the authors studied 58 women with breast implants (46 monolateral and 12 bilateral prostheses) by means of clinical examination, mammography, and US. The patients' age ranged 31-56 years (mean: 32). Thirty women had undergone subpectoral implantation, 22 subcutaneous and 18 retroglandular. In the group of subpectoral prostheses, 4 women had periprosthetic fibrosis and 3 presented benign calcifications; in 1 case both fibrosis and calcifications were observed. In the depiction of retroglandular implants, US appeared to be very useful: indeed, it detected 3 fibroadenomas and 5 cysts that had been missed at mammography. The only 2 breast carcinoma recurrences (1 non-palpable lesion, confirmed at surgery) were observed in patients with retrocutaneous prostheses. Both mammography and US currently play a major role in the follow-up of women with breast implants. Benign complications and breast cancers can be promptly detected even in patients with no palpable findings. PMID- 1502353 TI - [Mammary ductal system. Echographic features]. AB - Real-time breast US is useful in the evaluation of localized lesions. Our study was aimed at examining the US features of the ductolobular system in physiological condition. To this purpose, all breasts were imaged on the radial plane by rotating the probe around the nipple, thus depicting the ductal system from nipple to gland periphery. The patients were made to lie supine or to sit down. In order to depict small lobular excrescences, TV magnification was employed on the target areas. Five hundred and twenty asymptomatic women were evaluated with US; preliminary mammograms had been obtained in 440 of them. Any subject with prominent duct shadows on mammography or mammographic and/or US demonstration of focal lesions was excluded from the study. Different US patterns were observed in the ductolobular system, depending on patients' age, mammographic patterns, physiological hyperplasia during pregnancy and/or involution after pregnancy and lactation. The ductal branches were demonstrated by US only in mammographically dense areas. Thus, US has been observed to allow the evaluation of the physiological changes in the ductolobular system. PMID- 1502354 TI - [Invasive pulmonary aspergillosis: possibility of radiologic diagnosis]. AB - The incidence of invasive pulmonary aspergillosis is increasing in the patients with malignant hematologic diseases; this occurs in the phase of granulocytopenia induced by chemotherapy. In these cases an early diagnosis is mandatory to start a prompt antimycotic treatment. The authors reviewed the personal series of 56 patients with malignant hematologic diseases who, in the phase of granulocytopenia, developed a pulmonary lesion: 32/56 with invasive pulmonary aspergillosis; 8/56 with Candida and 16/56 with bacterial infection. All patients underwent several conventional radiologic controls: 9 cases with invasive pulmonary aspergillosis were also studied with Computed Tomography (CT). After a short pathologic introduction, the conventional radiologic and CT patterns of invasive pulmonary aspergillosis are analyzed, both at onset and over its evolutive phase. The most significant feature for an early conventional radiologic diagnosis is the nodular pattern--single or multiple--; this allowed a correct diagnosis, at onset, of 20/32 (62%) invasive pulmonary aspergillosis cases. CT provided a further diagnostic contribution by showing a peri-nodular halo. Of interest was also the CT demonstration of high-density pleural thickening adjacent to the mycotic lesion, probably due to fungal involvement of the sub-pleural space. The routine chest roentgenogram is the modality of choice; CT may be useful in questionable cases. PMID- 1502355 TI - [Atkinson prosthesis in esophageal carcinoma. Radiologic study: when CT?]. AB - The endoscopic palliative treatment of esophageal and esophagocardial neoplastic stenoses is generally performed in the patients in whom surgery is not indicated for oncological and general reasons and endoscopic dilatation is uneffective. Our experience is reported concerning 92 patients submitted to palliative therapy through placement of Atkinson prostheses; the patients underwent radiologic studies--i.e. (a) plain chest radiographs (before and after intubation), (b) esophagogastric studies with iodate cm, and (c) CT (performed in the last 20 cases only). The mortality rate at 30 days was 6.5% (6 cases), in no case due to specific complications related to intubation. The mean survival was 3.6 months (range: 1-12). As to the complications specifically related to intubation, they were basically 3: perforation, dislocation, and obstruction (of the prosthesis). As to the methods allowing best demonstration of the same: a) CT proved to be superior in revealing perforation, which usually occurs early after intubation. However, considering its low incidence (2 cases only, in our series), the routinary use of CT does not seem justified. CT should be reserved to selected patients in whom the shape of the neoplasm or peculiar anatomical conditions make intubation difficult, with high risks of perforation--e.g., kiphoscoliosis, hiatal hernia, previous surgery or radiotherapy, angulation of the prosthesis, neoplasm of scirrhous or necrotic type or causing luminal deviation; b) if dislocation occurs, as it more often happens (9 cases in our series) in the presence of soft neoplastic tissue or in cases of mild or asymmetrical stenosis, CT seems likewise unnecessary. Conventional radiology proved superior thanks to its more comprehensive view, and therefore sufficient to suggest the correct treatment--e.g. repositioning of the prosthesis by means of fiberoscopy, or withdrawal after gastrostomy; c) CT appeared useless in the cases due to alimentary causes (easily detectable from the clinical history), but proved useful in the cases due to neoplastic overgrowth. In the latter, CT can yield information as to the site and size of the neoplasm, as well as to its relationship to surrounding tissues, and thus help suggest proper treatment--e.g. dilatation and repositioning of the prosthesis, gastrostomy, recanalization by means of NdYAG laser, no treatment at all. PMID- 1502356 TI - [Radiologic assessment of extent of ulcerative colitis in acute phase]. AB - One of the major reference points for both prognosis and treatment of ulcerative colitis is the assessment of its extent. Plain abdominal radiographs were performed on 97 patients previously diagnosed, by means of rectoscopy and histobiopsy, as having acute ulcerative colitis. Within the following 36 hours they underwent either full colonoscopy or colectomy. The extent of colitis was evaluated by means of double-blind radiography. The results were then statistically compared with those obtained from endoscopy or from direct study of surgical colonic specimens. There was agreement between the final X-ray results and the actual extent of ulcerative colitis in 78 of 97 patients (80.4%, r = 0.86). The highest agreement was observed in those patients whose lesions were localized in the rectosigma (81%) and in those with fully extended colitis (90%). The most useful radiological findings in predicting the extent of colic lesions were irregular mucosal profile and thickening of colic wall. The presence of these two signs, together with the flattening or swelling of interhaustral folds and the impossible visualization of the right colon, are invariably suggestive of fully extended colitis. On the contrary, no abnormal findings were present on plain abdominal films in 74% of proctosigmoiditis cases. Plain abdominal radiography seems to be useful for the initial evaluation of acute ulcerative colitis. It allows the early discrimination between diffuse and localized forms, and makes it possible to postpone more invasive and dangerous investigations to a remissive phase of the disease. PMID- 1502357 TI - [Role of MR in characterizing expansive lesions of the adrenal gland]. AB - Five patients with adrenal tumors (20 metastases, 12 adenomas, 8 myelolipomas, 6 primary tumors, 4 pheochromocytomas, and 1 hyperplasia) were studied by means of MRI with SE sequences. Twenty of them underwent dynamic study with GE sequences after i.v. injection of paramagnetic contrast media. Sixteen of 20 metastases exhibited low signal intensity on T1 and high signal on T2. One patient had low signal on both T1 and T2. Two lesions in patients with melanoma showed high signal in T1; in 1 case, the lesion exhibited a hemorrhagic area. Signal from adenomas was low in T1- and T2-weighted pulse sequences in 10/12 patients, while in the extant 2 cases signal was higher in T2. Myelolipomas had hyperintense signal on T1-weighted images in 5 cases and isointense signal with the renal cortex in the extant 3 cases. Pheochromocytomas and primary tumors appeared hypointense on T1 and hyperintense on T2. In 3 CT questionable cases, MRI showed the adrenal origin of the lesion. Dynamic study with GE sequences after Gd-DTPA injection showed low enhancement and fast washout in adenomas, while malignant lesions had higher enhancement and slower washout. In our study, MRI allowed to correctly characterize 11/12 adenomas, with only 1 false negative in a metastatic lesion. PMID- 1502358 TI - [Hydronephrosis and peripelvic cysts. A new echographic sign for the differential diagnosis]. AB - The differential diagnosis of peripelvic cysts and hydronephrosis by means of US sometimes presents some problems; in fact, the use of urography to solve a diagnostic doubt is not uncommon. This study was aimed at demonstrating that another US sign, which we have called the "convexity" sign, can be useful in allowing peripelvic cysts to be distinguished from hydronephrosis. Thus, cysts exhibit convex walls and curved outline, whereas in hydronephrosis the walls of the dilated calices are linear. The latter feature is present in all degrees of hydronephrosis, except in severe cases. Forty-nine adult patients, a total of 98 kidneys, were examined with US and urography; 69 kidneys were found to be pathologic: 48 presented with cysts, and 21 with hydronephrosis. In addition to the new sign, the classic signs of peripelvic cysts were also considered, that is the separate areas and the non-visualization of the ureter. The sensitivity of the new sign was 97% and its specificity was 95%. The sensitivity and the specificity of the classic signs were 97% and 95%, respectively for the separated areas, and 100% and 91% for the non-visualization of the ureter. The cumulative sensitivity of the 3 signs was 99%, and their specificity 96%. Our results show how the integrated analysis of the considered signs (especially those with high specificity) is useful for the differential diagnosis, and therefore to avoid the indiscriminate use of urography. PMID- 1502359 TI - [Echographic features of urachal cysts]. AB - The authors discuss the anatomical, clinical, and US patterns of 5 cases of urachal cysts observed in pediatric patients (average age: 9.2 months) over the last 4 years. All cases had surgical confirmation. Linear and convex probes with 3.75, 5, and 7.5 MHz frequency were employed. Most of the observed lesions were oval in shape, their size ranging 3-6 cm; they were found in ventral-epivesical regions and had no mobility. Liquid echotexture with hyperechoic deposits on the lower layers was observed in 2 cases, and inhomogeneous solid or complex mass like echotexture in 3 cases (suppurated cysts). Differential diagnosis includes mesenteric cyst, simple and teratomatous ovarian cyst, bladder diverticulum and hydrometrocolpos. Echotomography exhibited high accuracy in detecting this kind of lesion and allowed guidance of percutaneous drainage for the preoperative treatment of infected cysts. Both cystography and CT appeared to be useless. PMID- 1502360 TI - [Percutaneous transcatheter embolization of deep visceral pseudoaneurysms]. AB - The authors present their experience with the percutaneous embolization of 13 splanchnic aneurysms and pseudoaneurysms (2 pseudoaneurysms of gastroduodenal artery, 3 of the hepatic artery, 7 renal pseudoaneurysms, 1 aneurysm of the splenic artery). In 9 of 13 cases the lesions were iatrogenic. Embolizing devices and techniques are described. Percutaneous embolization was successful in 12 of 13 cases, and useless in 1 case of renal pseudoaneurysm. In the 12 successfully treated cases the lesions were still occluded in the follow-up period. Transcatheter percutaneous embolization is the elective treatment in splanchnic aneurysms and pseudoaneurysms; surgery must be performed only when embolization fails. PMID- 1502361 TI - [Technical notes and clinical advantages of the use of a new pyelo-ureteral catheter]. PMID- 1502362 TI - [Low dose-rate intraesophageal irradiation]. PMID- 1502363 TI - [Comparison of acceptance tests of 5 linear electron accelerators for radiotherapy]. AB - The acceptance tests of five electron linear accelerators have been analyzed to compare their completeness, the standards specified by the manufacturers and the measured deviations. Involved tests were relative to geometrical and mechanical parameters, photon and electron beam characteristics, dose monitoring systems, treatment table and safety systems. The comparison of acceptance tests has shown a significant nonuniformity, also due to the absence of a specific legislation; anyway, the measured deviations generally appeared to be within internationally recommended values. PMID- 1502364 TI - [Pulmonary neoplasms in patients with heart transplantation]. PMID- 1502365 TI - [Cystic adenomatoid malformation of the lung. Presentation of a case]. PMID- 1502366 TI - [Mediastinal hemorrhage caused by spontaneous parathyroid hemorrhage in a patient in hemodialysis]. PMID- 1502367 TI - [Absence of liver accumulation of 67Ga-citrate in Pneumocystis carinii pneumonitis in AIDS. Description of a case]. PMID- 1502368 TI - [Computerized tomography diagnosis of left paraduodenal hernia. Description of a case]. PMID- 1502369 TI - [Computerized tomography features of giant pseudocyst of the colon. A case]. PMID- 1502370 TI - [Cysts of the seminal vesicles. Sonographic findings in 2 cases, one of them associated to homolateral renal agenesis]. PMID- 1502371 TI - [Too many congresses? Too many authors?]. PMID- 1502373 TI - The role of cancer risk in the regulation of industrial pollution. AB - The extent of carcinogen regulation under existing U.S. environmental statutes is assessed by developing measures of the scope and stringency of regulation. While concern about cancer risk has played an important political role in obtaining support for pollution control programs, it has not provided the predominant rationale for most regulatory actions taken to date. Less than 20% of all standards established to limit concentrations of chemicals in various media address carcinogens. Restrictions on chemical use are more frequently based on concerns about noncancer human health or ecological effects. Of the chemicals in commercial use which have been identified as potential human carcinogens on the basis of rodent bioassays, only a small proportion are regulated. There is an inverse relationship between the scope of regulatory coverage and the stringency of regulatory requirements: the largest percentages of identified carcinogens are affected by the least stringent requirements, such as information disclosure. Standards based on de minimis cancer risk levels have been established for only 10% of identified carcinogens and are restricted to one medium: water. Complete bans on use have affected very few chemicals. The general role that carcinogenicity now plays in the regulatory process is not dramatically different from that of other adverse human health effects: if a substance is identified as a hazard, it may eventually be subject to economically achievable and technically feasible restrictions. PMID- 1502372 TI - Structure and parameterization of pharmacokinetic models: their impact on model predictions. AB - There has been an increasing interest in physiologically based pharmacokinetic (PBPK) models in the area of risk assessment. The use of these models raises two important issues: (1) How good are PBPK models for predicting experimental kinetic data? (2) How is the variability in the model output affected by the number of parameters and the structure of the model? To examine these issues, we compared a five-compartment PBPK model, a three-compartment PBPK model, and nonphysiological compartmental models of benzene pharmacokinetics. Monte Carlo simulations were used to take into account the variability of the parameters. The models were fitted to three sets of experimental data and a hypothetical experiment was simulated with each model to provide a uniform basis for comparison. Two main results are presented: (1) the difference is larger between the predictions of the same model fitted to different data sets than between the predictions of different models fitted to the dame data; and (2) the type of data used to fit the model has a larger effect on the variability of the predictions than the type of model and the number of parameters. PMID- 1502374 TI - Bivariate distributions for height and weight of men and women in the United States. AB - For the U.S. population, we fit bivariate distributions to estimated numbers of men and women aged 18-74 years in cells representing 1 in. intervals in height and 10 lb intervals in weight. For each sex separately, the marginal histogram of height is well fit by a normal distribution. For men and women, respectively, the marginal histogram of weight is well fit and satisfactorily fit by a lognormal distribution. For men, the bivariate histogram is satisfactorily fit by a normal distribution between the height and the natural logarithm of weight. For women, the bivariate histogram is satisfactorily fit by two superposed normal distributions between the height and the natural logarithm of weight. The resulting distributions are suitable for use in public health risk assessments. PMID- 1502375 TI - An analysis of the uncertainties in estimates of radon-induced lung cancer. AB - A recent report by the National Academy of Sciences estimates that the radiation dose to the bronchial epithelium, per working level month (WLM) of radon daughter exposure, is about 30% lower for residential exposures than for exposures received in underground mines. Adjusting the previously published BEIR IV radon risk model accordingly, the unit risk for indoor exposures of the general population is about 2.2 x 10(-4) lung cancer deaths (lcd)/WLM. Using results from EPA's National Residential Radon Survey, the average radon level is estimated to be about 1.25 pCi/L, and the annual average exposure about 0.242 WLM. Based on these estimates, 13,600 radon-induced lcd/yr are projected for the United States. A quantitative uncertainty analysis was performed, which considers: statistical uncertainties in the epidemiological studies of radon-exposed miners; the dependence of risk on age at, and time since, exposure; the extrapolation of risk estimates from mines to homes based on comparative dosimetry; and uncertainties in the radon daughter levels in homes and in the average residential occupancy. Based on this assessment of the uncertainties in the unit risk and exposure estimates, an uncertainty range of 7000-30000 lcd/yr is derived. PMID- 1502376 TI - Microenvironmental analysis of residential exposure to chromium-laden wastes in and around New Jersey homes. AB - The purpose of this study was to identify the significant microenvironments that can lead to chromium exposure in Hudson County, New Jersey residential settings near or on soil contaminated with chromium waste. Measurements were made in indoor air, outdoor air, and house dust. Surface dust was found to be the best index of potential Cr exposure. The values of Cr in Hudson County household dust ranged from 3.25-320 ng/cm2 in wipe samples and 1.0-12 ng/cm2 in vacuum samples. Elevated Cr in household dust was found to be related to residential locations near large chromium waste sites, household cleaning habits, and house renovation activities. Outdoor Cr air levels were similar to those obtained in other urban areas at these seasons of the year, approximately 5-7 ng/m3. Comparisons with measurements of the Cr levels in urine found that the elevated Cr in dust was associated with elevated excretion of Cr. Site-specific Cr differences in household dust suggest different sources and routes of exposure. Within the total group of homes in the present study, Cr in household dust was the major influence on household exposure. PMID- 1502377 TI - Interspecies extrapolation: a reexamination of acute toxicity data. AB - We reanalyze the acute toxicity data on cancer chemotherapeutic agents compiled by Freireich et al.(1) and Schein et al.(2) to derive coefficients of the allometric equation for scaling toxic doses across species (toxic dose = a.[body weight]b). In doing so, we extend the analysis of Travis and White (Risk Analysis, 1988, 8, 119-125) by addressing uncertainties inherent in the analysis and by including the hamster data, previously not used. Through Monte Carlo sampling, we specifically account for measurement errors when deriving confidence intervals and testing hypotheses. Two hypotheses are considered: first, that the allometric scaling power (b) varies for chemicals of the type studied; second, that the same scaling power, or "scaling law," holds for all chemicals in the data set. Following the first hypothesis, in 95% of the cases the allometric power of body weight falls in the range from 0.42-0.97, with a population mean of 0.74. Assuming the second hypothesis to be true-that the same scaling law is followed for all chemicals-the maximum likelihood estimate of the scaling power is 0.74; confidence bounds on the mean depend on the size of measurement error assumed. Under a "best case" analysis, 95% confidence bounds on the mean are 0.71 and 0.77, similar to the results reported by Travis and White. For alternative assumptions regarding measurement error, the confidence intervals are larger and include 0.67, but not 1.00. Although a scaling power of about 0.75 provides the best fit to the data as a whole, a scaling power of 0.67, corresponding to scaling per unit surface area, is not rejected when the nonhomogeneity of variances is taken into account. Hence, both surface area and 0.75 power scaling are consistent with the Freireich et al. and Schein et al. data sets. To illustrate the potential impact of overestimating the scaling power, we compare reported human MTDs to values extrapolated from mouse LD10s. PMID- 1502378 TI - On the use of 0.75 as an interspecies scaling factor. PMID- 1502379 TI - Interspecies extrapolation of toxicity data. PMID- 1502380 TI - [Catamenial pneumothorax. Apropos of a case]. PMID- 1502381 TI - [Acute aseptic meningitis caused by herpes zoster]. PMID- 1502382 TI - [Accessory spleen. Differential diagnosis with Castleman's disease]. PMID- 1502383 TI - [Paralysis of the respiratory muscles in polymyositis. Treatment with cyclophosphamide pulses]. PMID- 1502384 TI - [Immediate efficacy of bromocriptine (BrC)-LAR in the treatment of macroprolactinomas: apropos of a case]. PMID- 1502385 TI - [Shock with 2 concomitant causes: sudden onset of autoimmune polyglandular syndrome type II]. PMID- 1502386 TI - [Acalculous hydronephrosis in Crohn disease treated with ureteral catheterization]. PMID- 1502387 TI - [Multiple pulmonary abscesses caused by Eikenella corrodens]. PMID- 1502388 TI - [Spinal cord disease as a presenting form of Paget's disease of bone with good clinical response to medical treatment]. PMID- 1502389 TI - [Immunotherapy and infection in Goodpasture's syndrome]. PMID- 1502390 TI - [Hepatitis A with biphasic and cholestatic course]. PMID- 1502391 TI - [Clinical relationship]. PMID- 1502392 TI - [Study of 94 cases of sarcoidosis with special reference to erythema nodosum]. AB - We studied 94 patients diagnosed of sarcoidosis in order to establish the incidence of erythema nodosum (EN), in the course of sarcoidosis, in our setting and to check if it induces different clinical and analytical characteristics in patients. 37 patients (39%) showed EN with a mean age of 41 +/- 1.62 years and with a marked female predominance (81%). Its presence was associated with a higher frequency of general symptoms (p less than 0.01), articular manifestations (p less than 0.001), specially in knees and ankles (p less than 0.01), subacute evolution (p less than 0.001), raise in GSR and of alpha-one-globulin (p less than 0.01) and hypoalbuminemia (p less than 0.05). On the other hand, those patients without EN showed higher frequency of dermal lesions different from EN (p less than 0.001) and the articular manifestations were localized preferentially in knees and proximal interphalangeal articulations of hands (p less than 0.05). We underline the high incidence of EN in sarcoidosis in our setting, which originates a more benign clinical type with a more favorable prognostic, embedded in the course of sarcoidosis, to which EN would transfer its clinical, analytical and immunopathogenic characteristics. PMID- 1502393 TI - [Evaluation of the incidence of nephrotoxicity associated with the use of aminoglycosides in patients with extrahepatic biliary obstruction]. AB - In the present publication we discuss nephrotoxicity (NT) incidence by reviewing all the clinical histories of one year (May 1989-May 1990) with diagnosis of obstructive jaundice or cholangitis. Of a total of 90 patients. 53 were treated with aminoglycosides and 37 received other antibiotics. Nephrotoxicity developed in nine patients of the group that received aminoglycosides (17%), versus only three patients (8%) in the other group. Both groups were comparable regarding sex, age and liver and renal basal functions. Analysis of the variables that could be associated with a higher incidence in the nephrotoxicity group that received aminoglycosides showed that there were no differences regarding age, sex, dosage, duration of treatment, plasmatic levels of aminoglycosides and liver and renal basal functions. Only simultaneous administration o furosemide was significantly associated with the development of nephrotoxicity. Results of this study underline the need of a prospective follow-up of patients with biliary obstruction during treatment with aminoglycosides. Meanwhile the evidence available allows us to recommend the monitoring of renal function in this type of patients. PMID- 1502394 TI - [Primary pulmonary leiomyoma. Presentation of 3 cases]. AB - Pulmonary leiomyoma is a benign tumor of mesodermal origin, very rare of which only three cases have been described on the Spanish scientific literature. We present our experience with three new cases and discuss the clinical and therapeutic characteristics of these neoplasms according to their topographical localization. We insist on the need of a gynecological revision when females are affected, because its possible association with uterine tumors. PMID- 1502395 TI - [Bisalbuminemia and bisalbuminuria: a study of a familial case]. AB - We present one case of hereditary bisalbuminuria and bisalbuminemia in a Spanish family with three affected members. The double band of albumin was detected accidentally in an routine analytical study of a patient who showed hyperuricemia, this originated the study of the rest of the members of the family. Protein electrophoresis, in serum as well as in urine, showed a double band of albumin, which as in most published cases corresponded to the slow migration type. With immunoelectrophoresis its immune identity with common albumin was established. The biochemical parameters assessed did not show any alteration which could correlate the protein disorder with any associated pathology. PMID- 1502397 TI - [Multiple pulmonary nodules as an unusual manifestation of pulmonary tuberculosis. Description of 3 cases]. AB - Pulmonary tuberculosis is still one of the more frequent diseases in our setting, adopting a wide variety of clinic as well as radiologic presentations. We present three cases of pulmonary tuberculosis with multiple bilateral pulmonary nodules of segmentary localization, one of them requiring thoracotomy to perform the diagnosis. PMID- 1502396 TI - [Lyme disease: 4 reported cases in the Autonomous Community of Aragon]. AB - Lyme's disease (LD) is a multisystemic infection due to Borrelia Burgdorferi transmitted through the byte of a vector arthropod of the Ixodes genre. Until now we do not know exactly which is the geographical distribution in our setting, no case have been published in the Aragon Community. We present four patients diagnosed of Lyme's disease following clinical and serological criteria (IFI) according to the recommendations of the Spanish Group for the study of Lyme's disease. A patient with Chronic Migratory Erythema (ECM); two others in stage II- one with predominant dermal lesions and other with predominant neurological symptoms--and finally, a patient in stage III with polyarticular symptoms and with antecedent of having showed a lymphocytic meningoencephalitis. PMID- 1502398 TI - [Subpleural pulmonary mass: radiography-CAT correlation]. PMID- 1502399 TI - [Alimentary factors and gastric cancer: design of a hospital based case-control study]. AB - One of the most widely used design in etiologic research is the case-control study. In the present work the methodology used in the design of a case-control study, performed in a hospital setting, which objectives was to verify etiological hypothesis related with food-intake and gastric adenocarcinoma and 234 controls from the population--188 selected through a randomized selection on the phone book and 46 following neighborhood criteria--are studied. The methodology and the development of the field work are described, with a special interest in the possible bias incurred during its design and development. PMID- 1502400 TI - [Hemostatic treatment of acute hemorrhage caused by esophageal varices. Time to ponder]. PMID- 1502401 TI - [Analysis of energy intake, macronutrients and micronutrients in a child population]. AB - With the objective to know precisely the qualitative and quantitative food intake of the infant population of a Health Care Area, the weekly intake of Energy, Proteins, Total and Saturated Fat, Food Fiber, Cholesterol, Calcium, Phosphorus, Magnesium. Iron, Zinc and Vitamin A is studied in 187 pupils, representative of the whole (835 children) population of two schools of Fuenlabrada and Leganes (Madrid), following the Weekly Register technique. Total consumption is quantified, and stratified according to sex and age groups. In order to perform a proper evaluation of these parameters, their adequacy to the Intake Recommendations for age and sex is analyzed, finding an excessive intake of calories, proteins and lipids in all age groups: being saturated Fat a third of the total daily Fat; Carbohydrates intake less than 50% of total energy, which would be desirable to maintain the nutritional ratio. Calcium intake, insufficient in some age group, together with the strong correlation proteins phosphorus as well as total and saturated Fat with Cholesterol of the diet, allow to conclude that the excessive protein intake is predominantly due to meat products. It is also noted the lower intake of Zinc, Calcium, Magnesium, as to the recommended in certain age groups, therefore said individuals are at risk to suffer deficit of these micronutrients. PMID- 1502402 TI - [Epidemiology of acute poisoning: a study of 851 cases detected in the southern area of the Madrid community in 1990]. AB - Epidemiology of acute intoxication (AI) must be reviewed periodically to know its trends, therefore, following a line of RESEARCH, we have studied the AI's attended on the Emergency Ward of Internal Medicine at Hospital Doce de Octubre (Madrid). We found that most of them are voluntary (93%): in females being predominant the suicide attempt and in males the AI secondary to illegal drugs use. Toxic drugs have been used in 96% on suicide attempts; the relative incidence of each drug does not vary, but AI with more than one toxic diminish. Within the non-drug toxics, illegal drugs come first, followed by alcohol. Drug addiction is the numerically most frequent antecedent; depression is predominant in suicide attempts, alcoholism is infrequent in ethyl AI. ICU admissions represent an intermediate figure in our country, mortality (most of them due to overdose) is similar to those of non-Spanish series. PMID- 1502403 TI - [Preliminary results of a program of home oxygen therapy using transtracheal catheter]. AB - We present our experience with oxygen-therapy with transtracheal catheter in the period between January 1990 and December 1991. This procedure was offered to 130 patients who met criteria of home oxygen-therapy being accepted only by twelve. Ten patients maintained oxygen-therapy with transtracheal catheter with excellent results and a notable improve in their quality of life. One patient died twenty three days after beginning the procedure, due to evolution of main disease finding no role of the catheter in the disease. Another patient showed a vagal reaction after placement of the catheter, which forced to perform resuscitation with connection to mechanical ventilation taking the catheter off because familiar request. Patients who benefit this type of oxygen-therapy the trans tracheal catheter has showed its usefulness. With few complications and showing no problems in its home handling. Oxygen savings with this technique have been of 55%. Trans-tracheal catheter was much more effective than face mask to correct desaturation after exercise (p less than 0.001). PMID- 1502404 TI - [Mixed semi-specific cutaneous myiasis]. AB - A case of mixed semi-specific cutaneous myiasis produced by larvae from Calliphora vicina Rob.-Desv. and Lucilia sericata Mg, in their third development stage, is described, as the first case in humans, although there is a precedent described in domestic animals. Main taxonomic characteristics and diagnostic features of the parasites are discussed, together with the implications of their biology in the observed clinical case, discussing, as well the prophylaxis and therapy. PMID- 1502405 TI - [Pulmonary lymphangiomatosis associated with renal angiomyolipoma. Presentation of a case and review of the literature]. AB - The case concerned is one of lymphangiomyomatosis (LAM) in a woman aged 39, that after a episode of spontaneous pneumothorax was subject to medical research for progressive dyspnea of medium efforts and bloodstained sputum. High resolution CT showed numerous thin-walled cystic airspaces of varying sizes distributed diffusely throughout the lungs. The abdominal CT and ultrasound developed multiple right renal angiomyolipomas. The histopathological study of the sample obtained by open lung biopsy was conclusive of LAM. The main feature of this rare disease, which occurs almost exclusively in women of reproductive age, is the abnormal proliferation of immature smooth muscle at the level of the distal airway, small blood vessels and lung lymphatic system, including sometimes the mediastinal and retroperitoneal lymphatic system. The clinical, functional, radiological and differential diagnostic aspects with entities histopathologically similarities are discussed and the therapeutic possibilities are reviewed. PMID- 1502406 TI - [Yellow nail syndrome: presentation of a case and review of the literature]. AB - We discuss the yellow nails syndrome which is constituted by yellow nails, pleural effusion and lymphedema. After reviewing the literature, it can be said that nail disorders are an early and constant sign, and its absence could put in doubt the diagnosis of this syndrome. The most frequent pleuro-pulmonary disorder is the pleural effusion, chylous or exudative type. It is believed that the origin of this disease could be a congenital hypoplasia of the lymphatic vessels. Lymphography and the morphologic study performed show a diminution in the number and size of the lymphatics vessels (lymphedema) which are hypoplastic, varicosities and tortuous dilations are sometimes observed. PMID- 1502407 TI - [Determination of glycosylated hemoglobin in clinical practice care of diabetes]. AB - At the end of 1989 a transversal study to know the availability of glycosylated hemoglobin as a control parameter in diabetic patients was done. Two hundred and three physicians-specialists in diabetes-provided information on the fraction, technique and reference interval used in their clinical practice. 90 +/- 4% of the participants were able to obtain, in their settings, the determination of glycosylated hemoglobin. Regarding work-places it is outstanding that 36 +/- 15% of the physicians in primary care did not have the possibility to get this parameter determined. Fraction and technique more widely used were, respectively, HbA1 and Ionic Interchange Chromatography performed with HPLC. There was no homogeneity in the reference intervals for HbA1 and HbA1c, considering different methodologies. The possibility to obtain different glycosylated hemoglobin determined, depends on the setting where the health care is being provided. It is important to know the reference interval of the Center where the determination is being done, in order to correctly interpret the glycosylated hemoglobin values of each patient. PMID- 1502408 TI - [Changing aspects of acquired immunodeficiency syndrome (AIDS)]. PMID- 1502409 TI - [Cushing's syndrome secondary to nasal instillation of dexamethasone]. PMID- 1502410 TI - [Gastric syphilis: an unusual case of secondary syphilis]. PMID- 1502411 TI - [Myelodysplastic syndrome following radioiodine treatment of differentiated carcinoma of the thyroid]. PMID- 1502412 TI - [Recurrent pericarditis caused by Q fever]. PMID- 1502413 TI - [Prognosis in non-melanoma skin cancer]. PMID- 1502414 TI - [Recurrent empyema caused by bronchial aspiration of a foreign body]. PMID- 1502415 TI - [Benefits of splenectomy in patients with chronic leukemia]. PMID- 1502416 TI - [Diagnostic problems in multiple pulmonary neoplasms]. PMID- 1502417 TI - [Magnesium sulfate in the treatment of asthma]. PMID- 1502418 TI - [The role of free oxygen radicals in myocardial damage from ischemia/reperfusion, in chronic obstructive bronchopneumopathy and in aging]. AB - During the last few years, several observations point out that oxygen-free radicals may play a pivotal role in the development of myocardial ischaemic/reperfusion injury, chronic obstructive pulmonary disease (COPD) and aging. With particular reference to acute myocardial ischaemic syndrome, these compounds may account for reperfusion-mediated ventricular arrhythmias, myocardial stunning and cell death. Such molecules may also be involved in lung damage during the course of COPD. In this regard, polymorphonuclear cell (PMN) recruitment at myocardial and/or lung level play an important role in oxygen-free radical overproduction. Several factors may, in fact, trigger PMN adhesion, respiratory burst and/or lysosomal enzyme release, this leading to a deleterious effect for the host. As far as elderly is concerned, evidence has been provided for a strict relationship between oxygen-free radical generation and metabolic rate. Nevertheless, the occurrence of PMN impaired functions and malnutrition in aged subjects gives rise to an enhanced synthesis of these compounds. All together, these findings outline the toxicity of oxygen-derived radicals and suggest the usefulness of a therapeutical approach to antagonize their effects. PMID- 1502419 TI - [Skin manifestations in 140 kidney transplants]. AB - Cutaneous lesions can be a significant problem in kidney transplant recipients. The AA report a clinical spectrum of iatrogenic, infectious, preneoplastic and neoplastic skin diseases in 140 renal transplant recipients observed, from march 1988 to july 1991, at the Catholic University in Rome. Iatrogenic skin manifestations were the most common, followed by infections of the skin and preneoplastic and neoplastic cutaneous lesions. PMID- 1502420 TI - [Food allergy and asthma]. AB - The prevalence of asthma in patients suffering from food allergy or food intolerance had been studied in 1339 subjects. Of them, 165 patients (12.8%) were affected by asthma. However only 77 (5.7%) had positive prick tests for food antigens and 52 of these have a significant benefit when a suitable oligoallergenic diet was introduced. 35 out of patients were positively tested with a double-blind food challenge. The most frequent food antigen involved were milk and its derivatives and cereals, but some importance have also the additives to the food. In conclusion, in our patients suffering from food allergy or food intolerance asthma was present in 12.8% of the cases, but in only 77 (5.7%) the symptoms might be due to diet. When tested with oligoallergenic diet or with food challenge the percentage of positivity fall to 3.9% and 2.6% respectively. PMID- 1502421 TI - Adrenomyeloneuropathy and hypothyroidism. A 15 year follow-up case report. AB - A case of adrenomyeloneuropathy with diffuse focal demyelination throughout the entire central nervous system, is described in a 29 years old, an adult male, who developed Addison's disease at 14 years of age. Since the age of 23 he has been affected by a progressive spastic paraparesis of the inferior limbs associated with urine incontinence. In the last two years reduced cerebral function, peripheral neuropathy, impotence, primary hypothyroidism and high levels of VLCFA plasma concentration have appeared. PMID- 1502422 TI - Primary empty sella syndrome and hypogonadotropic hypogonadism in young male patients. AB - Twelve male patients with absence of pubertal development and hypogonadotropic hypogonadism underwent a contrast-enhanced computed tomography of the sellar region and dynamic endocrine testing consisting of insulin-induced hypoglycemia, GnRH and TRH test. In two patients, clinically indistinguishable from the others, the presence of an empty sella turcica was demonstrated. They also showed, in comparison with patients with normal sellar morphology, an absent prolactin response to hypoglycemia with otherwise normal pituitary function. Empty sella, either due to congenital incompetence of the diaphragma sellae or to pituitary shrinkage due to regressive changes by hemorrhage, infarction and possibly autoimmune phenomena, may rarely be associated with hypogonadotropic hypogonadism. PMID- 1502423 TI - [The articular sequelae of rheumatic fever: Jaccoud's dislocation arthritis. A case report]. AB - A case of rheumatic fever with severe heart involvement, in which articular rheumatoid-like features involving both hands appeared many years after clinical onset, is described. After reviewing the articular sequelae of rheumatic fever and describing the clinical features of each form, the authors point out the main differences between rheumatic fever and rheumatoid arthritis, and diagnose Jaccoud's arthritis. PMID- 1502424 TI - [Osteosclerotic micromolecular plasmacytoma]. AB - We describe a patient with a k light-chain myeloma revealed by an apparently solitary mixed lytic and sclerotic rib lesion. This rare manifestation may be explained by a still balanced bone remodeling in the early phases of the disease. PMID- 1502425 TI - [The locoregional treatment of neoplastic ascites with interferon-beta]. AB - Peritoneal effusion recurrence is one of the most important problem in the palliative management of patients with gastrointestinal malignancies and ovarian cancer. Ten patients with recurrent malignant ascites (three with ovarian cancer, two with pancreas cancer, two with gastric adenocarcinoma and one affected by colon cancer, one patient with peritoneal carcinomatosis, one subject with pleural mesothelioma surgically treated that after three years showed a peritoneal metastases and ascites), were treated with intraperitoneal beta interferon. In all patients a Tenckoff's catheter for peritoneal dialysis was introduced and peritoneal effusion extracted and measured. Three millions of beta interferon in saline solution was infused in peritoneal cavity every three days for nine days. Successively twenty millions every three days for nine days. In the 50% of patients a significant reduction of peritoneal effusion was observed. The locoregional therapy with beta interferon is proposed in palliative management of malignant ascites. PMID- 1502426 TI - [The nimodipine therapy of acute focal cerebral ischemia (minor stroke). A clinical study with an assessment of regional cerebral blood flow by SPECT]. AB - Aim of the study is the evaluation of therapeutic effectiveness of nimodipine in acute focal cerebral ischaemia. Thirty patients affected by minor ischaemic stroke divided in two randomized groups have been studied consecutively: all the patients were treated with standard therapy, nimodipine was delivered in addition only to the patients of the first group. Both clinical evaluation using Mathew scale, modified by Gelmers, and flowmetric evaluation with SPECT were performed at different times. The results haven't shown any significant statistical difference in the effectiveness of the therapy between the two groups even if a positive clinical trend was evidenced in the group treated with nimodipine. The flowmetric study has shown the poor homogeneity of the groups from a physiopathological point of view not-with-standing the two groups were similar for the clinical severity, sex, age and vascular risk factors. We conclude that is advisable to carry out further trials in which the comparison study groups are more numerous and balanced also from a physiopathological point of view. PMID- 1502427 TI - The neuro-immune network. Some recent developments. AB - Neuroimmunomodulation encompasses, by definition, numerous components and activities primarily derived from the immune system, and treats the immunoneuroendocrine interconnections at different levels of the integrated whole functioning organism. The arbitrary unit of the immunoneuroendocrine network is the immune microenvironment composed of lymphocytes, neurons, endocrine cells, nonlymphoid accessory cells, humoral factors from immune, nervous, endocrine and other tissues, receptors for endogenous and exogenous ligands, pathways for transduction of biological signals, physiological ions, various magnetic and electromagnetic compartments, and impulses from the higher nervous activity (the mind, the psyche). The neuroimmunomodulation is a marvelous mechanism from which arises an amazing quantity of variables and intercommunications in the living organism. Being a multidisciplinary science par excellence, neuroimmunomodulation is strongly antidogmatic and favors multidirectional organization of research. That means that actions of the immune, nervous and endocrine systems should be studied together in terms of intercommunications among identifiable structures and processes. Therefore, research endeavors in neuroimmunomodulation have different directions with seminal discoveries much too numerous to list here. This mini-review is confined to some recent findings dealing with the immunomodulatory activity of micromagnetic fields when applied to the brain, the humoral and cell-mediated components of certain neurological and psychiatric diseases, the autoimmune features in heroin addicts in relation to dementia and HIV infection, the neuroimmunobiology of lithium cation, and the in vivo immune function of enkephalins, and methionine-enkephalin in particular. PMID- 1502428 TI - Sexual dysfunction in selected neurologic disorders: hypothalamopituitary disorders, epilepsy, myelopathies, polyneuropathies, and sacral nerve lesions. PMID- 1502429 TI - Sexual aspects of multiple sclerosis. PMID- 1502430 TI - Sexual aspects of Parkinson's disease. PMID- 1502431 TI - A note on impotence in Guillain-Barre syndrome. PMID- 1502432 TI - Sexuality and mental retardation. PMID- 1502433 TI - Sexuality and chronic illness: biopsychosocial approach. PMID- 1502435 TI - Sexual function in neurologic disorders. PMID- 1502434 TI - Freud und Sechs. PMID- 1502436 TI - Aspects of genital physiology and pathology. PMID- 1502437 TI - Penile erection in men with spinal cord or cauda equina lesions. PMID- 1502438 TI - [The rights of the citizen]. PMID- 1502439 TI - [Nurses in the university?]. PMID- 1502440 TI - [The knowledge of pharmacological therapy of a group of Calabrian nurses. The Cultural Association of Nurses of Catanzaro and the Ospedale di Matera Working Group]. AB - Results of a surveys on nurses' knowledge on drugs, conducted by a group of nurses from 10 hospitals of Calabria Region, are presented. Data were specifically collected on: a. drug cocktails in parenteral infusions, b. antibiotic prophylaxis for medical and surgical patients, c. side effects of drugs, according to nurses perception and d. conflicts between nurses and doctors on drug therapy. Results, though not to be considered representative of the real practice, on the large number of cocktails administered to patients and the wide range of antibiotics used for medical and surgical prophylaxis, evidence how wide is the gap between theoretical principles and practice. The importance of a sound pharmacological knowledge on drugs in order to enable nurses to monitor practice and open a constructive dialog with doctors on drug therapies is stressed. PMID- 1502441 TI - [Group educational intervention in diabetic foot: the objectives, pedagogical strategies, level of knowledge and results]. AB - Detailed contents and aims of an educational intervention for diabetic foot are presented, together with evaluation tools and results at 3, 6 and 12 month interval after the course. Knowledge level and "health" of the foot were assessed at 12 month interval on 2/3 of the 100 diabetic patients originally exposed to the educational intervention. After 12 months 80% of patients showed a good retention of knowledge on practical issues related to foot care, while 77% of patients with persistent foot problems were not independent (because of hypo mobility or sight problems) in foot care. PMID- 1502442 TI - [Initiatives of the Rivista dell'infermiere]. AB - Several research, reflection and work proposals had been published in Rivista dell'infermiere during the past 6 years, with the double aim of starting a dialogue with the reading public and activating research projects. Some of the proposals were carried out and published, some are still at proposal level. A list of proposals presented, divided according main subjects, are presented together with a request to readers to suggest which one Rivista dell'infermiere should develop in the next two years. PMID- 1502443 TI - [Allergies]. PMID- 1502444 TI - [Fractures of the middle third of the face in children: anatomo-clinical, diagnostic and therapeutic characteristics]. PMID- 1502445 TI - [Reconstruction of the function and shape of the middle region of the face]. AB - The anatomical structures and biomechanical features of the middle third of the face require various methods of osteosynthesis in case of fracture. Compression osteosynthesis is mainly confined to the lateral margin of the orbits, where the transverse section of the bone is made so as to resist the force applied to attach the osteosynthetic material. If thin bone blades are fractured, as is often observed in the middle level of the face, adapting osteosynthesis is a method operating without compression. It can be regarded as the method of choice for this type of fracture. PMID- 1502446 TI - [Bilateral temporomandibular joint ankylosis in severe adult-onset Still's disease]. PMID- 1502447 TI - [Traumatic rupture of the levator tendon of the upper eyelid]. AB - We report on two cases of traumatic desinsertion of levator aponeurosis. After a blunt trauma diagnosis between levator aponeurosis desinsertion and neurogenic ptosis is important in planing the treatment: early surgery for the first and foregoing for the later. PMID- 1502448 TI - [The value of computer reconstruction of the frontal and sagittal planes of the facial structures]. AB - The authors evaluate the merits of computer reconstructions in the coronal and sagittal planes to assess the anatomy of the facial structures. If the patient can be kept motionless, the coronal plane provides information similar to those obtained by a study with direct sections. The ethmoidofrontal recesses, the lamina cribrosa, the thin relief of the middle meatus, the floor of the orbit are perfectly examined. The sagittal plane provides a new approach of the anterior and posterior cortical bone, of the frontal sinus, of the nasofrontal canal, of the ethmoidal cells, of the sphenoid sinus and of the vault of the palate. PMID- 1502449 TI - [Materials and infection in oral medicine and maxillofacial surgery]. PMID- 1502450 TI - [The maxillofacial surgeon faced with the HIV-positive patient: risks and prevention]. AB - Prevention against the transmission of the HIV must be universal today, which means that it applies to all patients. Blood, tissues, the CSF are infected, but nasal secreta, tears and saliva are not contaminated unless they contain blood. The statistical risk of an HIV serological conversion when making an injection is an estimate of 0.1 to 0.3%, one hundred times less than with the hepatitis B virus. The best protection for maxillofacial surgeons, who are very exposed by the manipulation of objects (needle, wires) and by considerable projections of blood (rotary motor) is not a systematic HIV serological test for all patients, but goggles with side screens, a double pair of gloves and the use of an antiseptic acting on the HIV in case of staining. PMID- 1502451 TI - [Current evaluation of a self-snapping screw system in traumatologic and orthodontic surgery]. AB - Since the first description in 1970, by F. X. Michelet, of the use of the mini plate system in maxillo-facial surgery, if the fundamental principles remain the same, the equipment has been constantly improved. The plates have been modified in structure and shape, the screws becoming self-tapping and self-drilling and finally self-breaking. The head of the screw has diminished to the point of not going over the level of the plate. The ancillary material is now more performing and easier to use. The authors have presented 3 years ago a new self breaking screw of which they now explain the technical and biomechanical bases, the necessities and the indications insisting on the numerous advantages of this system. PMID- 1502452 TI - [Fractures of the orbit floor. Advances in radiologic imagery]. PMID- 1502453 TI - [Cancer of the upper facial structures: apropos of 241 cases]. PMID- 1502454 TI - [A prosthesis following reconstruction using a micro-anastomosed gastro-epiploic flap in oncology]. PMID- 1502455 TI - [Post-irradiation lingual pain following curietherapy. Excluding recurrence]. PMID- 1502456 TI - [Immediate palatal obturator prosthesis after oncologic surgery]. PMID- 1502457 TI - [A new approach in the study of dry mouth. Apropos of 50 cases]. PMID- 1502458 TI - [Calcinosis of the temporomandibular joint: apropos of a case and critical review of the literature]. AB - We report a case of calcinosis of the temporo-mandibular joint. This microcrystalline arthropathy by deposits of calcium pyrophosphate crystals is exceptional at this level; it is necessary to look for other localizations joints to diagnose articular chondrocalcinosis. The local prognosis is the same with surgical treatment in case of articular destruction or significant deposits. PMID- 1502459 TI - [Mountain sports: their role in 2200 facial injuries occurring over 4 years at the University Hospital Center in Grenoble]. AB - Injuries caused by mountain sports account for many of the injuries admitted to the University Hospital of Grenoble. Out of 4,490 traumas, 470 were injuries sustained during the practice of mountain sports. While the frequency of these accidents does not evolve much, the etiological distribution depends on fashion. Thus an increasing number of lesions caused by cross-country biking has been noted during the past two years. We find it urgent to propose protective measures adapted to this new sport. PMID- 1502460 TI - [Malformed callus: etiologic factors]. PMID- 1502461 TI - [Malformed callus of the mandible: functional and esthetic correction]. PMID- 1502462 TI - [Baldness: flaps or grafts]. PMID- 1502463 TI - [Whose nose?]. PMID- 1502464 TI - [The value of selective grinding of the piriform cavity in Lefort I orthognathic surgery]. PMID- 1502465 TI - [Radio-opaque bridges and computed x-ray tomography]. PMID- 1502467 TI - [Mechanical effects related to Branemark implants]. PMID- 1502466 TI - [The surface finishing of surgical and dental implants (value and difficulties)]. PMID- 1502468 TI - [Mandibular ramus implant framework. 10 years' experience]. PMID- 1502469 TI - [The surgical treatment of sagittal fractures of the mandibular condyle]. PMID- 1502470 TI - The combination of a screw with a miniplate for the therapy of dislocated collum fractures. PMID- 1502471 TI - [Anatomy and imagery of the deep regions of the face]. PMID- 1502472 TI - [The contribution of scanner imagery in implant surgery and sinus overflow using frontal oblique orthogonal reconstruction]. PMID- 1502473 TI - [Severe atrophy of the alveolar ridge in edentulous patients. Combined treatment using bone grafts and screw implants]. AB - In cases of advanced alveolar ridge atrophy, when the bone available for endosseous implants is not sufficient, endosseous implants are combined with augmentation of the alveolar ridge by means of autologous bone transplants. Depending on the type of atrophy found, the authors use three different surgical procedures: onlay technique, sandwich technique and alveolar extension technique. In all cases functional loading of the implants was performed by way of an entirely implant-supported bridgework. Results to date indicate that initial postoperative resorption is followed by a virtual standstill once the implants have been loaded. PMID- 1502474 TI - [Dental implants. The contribution of iliac bone grafts]. PMID- 1502475 TI - [The value of sonography]. PMID- 1502476 TI - Cholecystokinin and the regulation of insulin secretion. PMID- 1502477 TI - Tumour markers CA 19-9 and CA 50 in digestive tract malignancies. AB - CA 19-9 and CA 50 are tumour marker tests measuring the same carbohydrate structure, sialosyl-fucosyl-lactotetraose--that is, the sialylated Lewis blood group antigen. In addition, the C50 antibody reacts with sialosyl-lactotetraose, which may be expressed in small amounts in some carcinomas. In this study we compared these tests in sera from patients with benign and malignant digestive tract diseases. The sensitivity of the markers for different cancers was also compared at several specificity levels with patients with benign diseases as reference groups. Both markers showed a high sensitivity for pancreatic cancer (77% for CA 19-9; 69% for CA 50) and biliary cancer (88%). The figures in colorectal cancer were almost as high as those reported for CEA; 16-21% elevated values in Dukes A and B tumours and 44-47% in Dukes C and D tumours. The sensitivity for gastric cancer was 48% for both markers. CA 50 had a higher sensitivity for liver cancer (55%) than CA 19-9 (9%), but the proportion of elevated values in benign liver diseases was also higher (33% versus 15%, respectively). Overall, there was good correlation between the CA 19-9 and CA 50 levels, and the difference in sensitivity and specificity was marginal. In clinical practice the greatest value of CA 19-9 and CA 50 is in the diagnosis of pancreatic cancer. PMID- 1502478 TI - Effect of cisapride on relapse of reflux oesophagitis, healed with an antisecretory drug. AB - Maintenance treatment with cisapride was evaluated in 298 patients in whom reflux oesophagitis had been healed with antisecretory drugs. Initially, 34% of the patients had grade-I oesophagitis, 33% had grade II, and 33% had grade III. The patients were treated with 20 mg cisapride twice daily or placebo for 6 months or until endoscopic relapse was shown if this occurred earlier. Survival analysis showed that cisapride significantly prolonged the time to endoscopic relapse in grade-I patients (P = 0.02). The intergroup difference in symptomatic relapse in all patients was also significant (P = 0.010). The effect of cisapride was less clearcut in grade II or III, and/or in patients healed with omeprazole. Factors associated with early relapse were placebo therapy, prior omeprazole therapy, duration of pre-trial symptomatic period, and initial endoscopic severity grade. Adverse experiences were limited; diarrhoea was reported by 9% of the cisapride patients. PMID- 1502479 TI - A model of inflammatory bowel disease induced by 2,4-dinitrofluorobenzene in previously sensitized BALB-c mice. AB - The aim of this study was to develop a model of inflammatory bowel disease (IBD) induced by colonic application of 2,4-dinitrofluorobenzene in previously sensitized BALB-c mice. During the follow-up period of 30 days we observed ulcerations, haemorrhage, necrosis, and mononuclear infiltration in the colonic mucosa of previously sensitized (experimental) and, to a lesser extent, nonsensitized (control) animals. In addition, the animals in the experimental group developed adhesions, thickening of colonic segments, stenosis, and dilatation of the colon, and some animals also developed megacolon. Oedema, mononuclear infiltration, and superficial ulcerations were observed in the ileum of experimental animals and, to a lesser extent, in the control group. In addition, the animals in the experimental group developed extraintestinal changes in the liver and spleen (that is, pericholangitis and lymphofollicular proliferation). We suggest that this model of IBD may have some value for the study of early pathogenetic mechanisms of IBD and for developing new therapeutic modalities for this condition. PMID- 1502480 TI - Cimetidine on-demand in dyspepsia. Experience with randomized controlled single subject trials. AB - Double-blind randomized controlled trials in single subjects (N of 1 RCTs) have demonstrated a beneficial symptomatic effect of cimetidine in reflux- or ulcer like non-ulcer dyspepsia (NUD). However, spontaneous fluctuations in symptoms reduce the validity of such trials when performed as continuous trials with fixed dosages. This study was carried out to identify individual responders to cimetidine in NUD, peptic ulcer disease, and oesophagitis and to confirm the beneficial average effect of cimetidine in these clinical entities. We evaluated N of 1 multi-crossover trial designs, which compare the effects of single doses of cimetidine and placebo taken on-demand for symptomatic relief. Each trial consisted of six cimetidine (400 mg or 800 mg) and six placebo tablets randomized in successive pairs. The symptomatic effect of each tablet was measured 1/2-6 h after the intake. Outcomes were assessed by individual p values and confidence intervals. A minimal clinically important difference was defined, to assess the clinical significance as demonstrated by the confidence intervals. Thirteen of 25 patients (52%) with reflux- and ulcer-like NUD obtained individual p values below 0.20. Similarly, 7 of 9 patients (78%) with oesophagitis and 6 of 12 patients (50%) with peptic ulcer obtained such p values. On the basis of the 80% confidence intervals the corresponding numbers of subjects with clinically significant effect were six (NUD), three, and three. The combined data showed a significantly better effect of cimetidine than of placebo (p less than 0.0001) in each of the three diagnostic groups studied. Cimetidine taken on-demand may have a rapid symptom-relieving effect in dyspepsia.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1502481 TI - The effect of dietary yeast on the activity of stable chronic Crohn's disease. AB - The effect of dietary yeast on the activity of stable Crohn's disease was assessed in 19 patients. During the 1st month patients continued their usual diet (base-line period), but during the next 2 months dietary yeast was excluded except that during 1 month patients took baker's yeast capsules while for the other month they took placebo capsules. The patients' mean Pettit Crohn's disease activity index (CDAI) while taking baker's yeast (mean, 107.9; SE, 6.1) was significantly greater than during yeast exclusion (mean, 102.1; SE, 5.7; p less than 0.05). The mean of each patient's maximum CDAI during yeast exclusion (mean, 107.1; SE, 5.7) was significantly lower than those during the base-line (mean, 115.2; SE, 6.1; p less than 0.05) and baker's yeast inclusion periods (mean, 113.9; SE, 6.7; p less than 0.05). Patients with elevated yeast antibodies tended to develop a higher CDAI while receiving baker's yeast (13 of 15). These results suggest that dietary yeast may affect the activity of Crohn's disease. PMID- 1502482 TI - Bile acid malabsorption caused by gastrointestinal motility dysfunction? An investigation of gastrointestinal disturbances in familial amyloidosis with polyneuropathy. AB - Gastrointestinal dysfunction due to autonomous neuropathy is a complication described in various diseases such as diabetes mellitus, multiple sclerosis, and familial amyloidosis with polyneuropathy. We present the results of a prospective investigation of bile acid malabsorption in 17 patients with familial amyloidosis by means of 75Se-labelled homocholic-tauro acid (SeHCAT). The diagnosis was in all cases verified by the DNA test for mutation of transthyretin in position 30. Small-intestinal biopsy specimens were examined for deposits of amyloid, and the presence of gastric retention was evaluated by gastroscopy. In addition, the patients were investigated for bacterial overgrowth by means of the bile acid breath test (BABT). A high frequency of abnormal BABT results (44%) was encountered. However, 65% also had abnormal low SeHCAT values, indicating bile acid malabsorption. Only two patients had abnormal BABT and normal SeHCAT results, indicating bacterial contamination of the small intestine. Bile acid losses increased with the duration of gastrointestinal symptoms. Significantly lower SeHCAT values were encountered in patients with gastric retention, whereas the occurrence of amyloid deposits in small-intestinal biopsy specimens was without effect on SeHCAT retention. Bile acid malabsorption is frequently encountered in familial amyloidosis with polyneuropathy and seems to be more closely associated with gastrointestinal motility dysfunction than with amyloid deposits in the intestinal mucosa. PMID- 1502483 TI - Influence of smoking on basal and on vagally and maximally stimulated gastric acid and pepsin secretion. AB - Published data show that smokers have greater basal or peak acid and pepsin outputs, but the mechanisms underlying these effects are unknown. To confirm this and to determine whether these findings extend to, and implicate, any vagal overactivity, gastric secretions collected for 1 h basally, 1 h after 15 min of modified sham feeding (MSF), and 1 h after pentagastrin (6 micrograms/kg subcutaneously) were analyzed for acid and pepsin content in 204 subjects, 104 with duodenal ulcer (66 smokers) and 101 without (57 smokers). Maximal acid outputs (MAO, mu eq/kg/h, means +/- SEM) were higher in smokers than in non smokers in both duodenal ulcer (DU) (623 +/- 35 versus 491 +/- 35, p less than 0.005) and non-DU (502 +/- 32 versus 376 +/- 20, p less than 0.005). Basal and MSF secretions were generally increased in smokers but, when expressed as a percentage of MAO, were not different in smokers and non-smokers (18% versus 17% and 43% versus 39%, respectively, in DU, and 13% versus 16% and 40% versus 36% in non-DU). Maximal pepsin outputs (units x 10(-2)/kg/h) were also higher in smokers than in non-smokers (DU, 129 +/- 7.9 versus 105 +/- 9.5, p = 0.05, and non-DU, 101 +/- 7.5 versus 77 +/- 10, p = 0.05). Basal and MSF secretions as a percentage of maximal pepsin output were not different in smokers versus non-smokers. Multivariate logistic regression shows that smoking was most strongly associated with MAO and sham feeding outputs, but the duration-intensity (pack-years) of smoking was associated only with elevated MAO.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1502484 TI - Cisapride treatment of patients with non-ulcer dyspepsia and erosive prepyloric changes. A double-blind, placebo-controlled trial. AB - One hundred and twenty consecutive outpatients with non-ulcer dyspepsia (NUD) and erosive prepyloric changes (EPC) were, after a 2-week placebo run-in period, randomly allocated to double-blind treatment with either 10-mg cisapride tablets or placebo three times daily for 4 weeks. The patients' global evaluation and total symptom score were significantly in favour of cisapride at 2 weeks (p less than 0.05). At 4 weeks the effect of cisapride was no longer significant (p = 0.22). Similarly, the investigators' global evaluation showed marked to moderate symptom improvement in 47% of the cisapride-treated patients as compared with 30% of the placebo-treated patients at 2 weeks. The 95% confidence interval of the difference (18%) was 0% to 35%. At 4 weeks the intergroup difference was only 10% (cisapride, 50% versus placebo 40%). Pain on awakening was the only symptom improved in favour of cisapride at 4 weeks. Thus, when patients with NUD and EPC are treated with cisapride, the therapeutic gain might vanish after the 2nd week of treatment. PMID- 1502485 TI - Helicobacter pylori-related hypergastrinaemia is not due to elevated antral surface pH. Studies with antral alkalinisation. AB - It has been postulated that Helicobacter pylori-related hypergastrinaemia is due to bacterial ammonia raising antral surface pH and thus preventing acid inhibition of gastrin release. If true, the infection should not alter gastrin release at neutral intragastric pH. To test this, we have studied basal and meal stimulated gastrin at uncontrolled pH and at pH greater than 6 in duodenal ulcer patients before and after eradication of H. pylori. The median integrated gastrin response to the meal alone was 2525 ng/l.min (range, 550-8725) before and 725 ng/l.min (range, 250-2925) after eradication of H. pylori (p less than 0.01). The corresponding values when intragastric pH was maintained above 6 were 3700 ng/l.min (range, 1900-14,100) and 1400 ng/l.min (range, 400-3400) (p less than 0.01). The median reduction in gastrin after eradication of H. pylori was thus similar when the meal was taken at uncontrolled pH (61%; range, 0-97%) and at pH greater than 6 (69%; range, 36-89%). Likewise, 5 h of gastric alkalinisation did not cause the basal gastrin values when H. pylori was eradicated to increase to those observed when H. pylori was present. These findings indicate that the hypergastrinaemia is not due to elevated antral surface pH. PMID- 1502486 TI - Effects of acute pancreatitis on hepatic secretion of lysosomal enzymes into bile and hepatic lysosomal fragility: protective effects of a new synthetic protease inhibitor, ONO 3307. AB - To evaluate the effects of acute pancreatitis on hepatic function and hepatic cellular and subcellular organellar fragility, we studied 1) the hepatic secretion of lysosomal enzymes (beta-glucuronidase, beta-galactosidase, and N acetyl-beta-glucosaminidase) into bile in the isolated perfused rat liver model; 2) the aspartate aminotransferase (ASAT), alanine aminotransferase (ALAT), and lysosomal enzyme levels in the effluent in an isolated liver model; 3) hepatic lysosomal fragility in an in vitro incubation study; and 4) protective effects of a new low molecular weight synthetic protease inhibitor, ONO 3307, against hepatic injury in doses of 2 and 5 mg/kg.h in acute pancreatitis induced by a supramaximal dose of cerulein in rats. Decreased hepatic secretion of lysosomal enzymes into bile and accelerated hepatic lysosomal fragility were observed in acute pancreatitis induced by cerulein. ONO 3307 showed a significant protective effect against this hepatic injury in acute pancreatitis, the dose of 5 mg/kg.h showing a more potent effect than the dose of 2 mg/kg.h. These results suggest that the impaired hepatic function, including depressed hepatic secretion of lysosomal enzymes, seems to be closely related to accelerated hepatic fragility and that some unknown protease, which is present in pancreatitis and is susceptible to inhibition by ONO 3307, plays a crucial pathologic role in the development of this liver injury during acute pancreatitis. PMID- 1502487 TI - Erosive prepyloric changes in dyspeptics and non-dyspeptics in a defined population. The Sorreisa Gastrointestinal Disorder Study. AB - In this population-based endoscopic survey we found erosive prepyloric changes (EPC) in 38.5% of dyspeptics and 35.1% of non-dyspeptics. EPC were observed more frequently in men than in women in both groups. Occurrence of Helicobacter pylori was not associated with EPC. No common gastrointestinal symptoms were found to be associated with EPC. Endoscopic duodenitis of the duodenal bulb was found more frequently in subjects with EPC of the two highest grades than in subjects without EPC. Only the highest grade of EPC was associated with chronic gastritis. EPC were associated with cigarette smoking and, among women, also use of alcohol. We conclude that EPC constitute an endoscopic finding without relation to specific symptoms. These changes therefore do not represent a clinical entity, and it is doubtful whether this finding will give the clinician a better understanding of dyspepsia. PMID- 1502488 TI - Influence of dehydrocholic and cholic acids on the biliary secretion of anionic polypeptide fraction, the major apoprotein of the biliary lipoprotein complex. AB - This work was undertaken to study the effect of intravenously infused dehydrocholate (DHCA) and cholate (CA) on lipid and anionic polypeptide fraction (APF) secretion in bile. APF is a small acidic amphipathic apoprotein closely associated with biliary lipids and bilirubin and involved in the control of bile destined cholesterol. Rats were infused with increasing doses of DHCA (2 and 3 mumols/min/100 g b.w.) and then CA (1, 2, and 3 mumols/min/100 g b.w.). Each dose was infused for 30 min. As expected, intravenous DHCA inhibited biliary phospholipid (PL) and cholesterol secretion, and CA restored it. When DHCA was infused, the level of APF increased fourfold compared with controls. The APF/PL ratio also increased, but biliary albumin remained stable. When bile secretion was stimulated by infusion of CA, biliary APF returned to normal. These data indicate that biliary secretion of APF depends on the nature and the amount of bile salts returning to the liver, and consequently, APF can be considered a marker of bile secretion disorders. PMID- 1502489 TI - Antrectomy does not accelerate reversal of omeprazole-induced trophic effects in the rat stomach. AB - The oxyntic mucosa in the rat stomach is under the influence of circulating gastrin. The histamine-producing enterochromaffin-like (ECL) cells constitute the major endocrine cell population in the oxyntic mucosa. They are notably sensitive to changes in the serum gastrin concentration and respond to long-term hypergastrinemia with hyperplasia, whereas hypogastrinemia induces hypoplasia. In the present study long-term, sustained hypergastrinemia was induced by daily treatment with a high dose of the proton pump inhibitor omeprazole. After 10 weeks omeprazole-treated and control rats were antrectomized, resulting in prompt hypogastrinemia. Antrectomy was followed by a rapid reduction of the thickness of the oxyntic mucosa and a somewhat slower reduction of the ECL cell number in both omeprazole-treated and control rats. The percentage decrease in the ECL cell number with time was similar in both groups; after 2-3 weeks the ECL cell number was half of that before antrectomy in both groups. Interestingly, however, 12 weeks after antrectomy the ECL cell number in the omeprazole-pretreated rats remained elevated compared with untreated rats. The histamine concentration of the oxyntic mucosa was markedly lowered within a week after antrectomy in both omeprazole-treated and control rats. Although antrectomy induces hypogastrinemia and although atrophy develops rapidly in the oxyntic mucosa, the omeprazole induced ECL cell hyperplasia was not completely reversed by antrectomy during the 12 weeks of examination. PMID- 1502490 TI - Double-blind randomized trial of bismuth subsalicylate and clindamycin for treatment of Helicobacter pylori infection. AB - We evaluated clindamycin and bismuth subsalicylate (Pepto-Bismol) for treatment of Helicobacter pylori infection. Patients with culture or histology positive for H. pylori were randomized to receive two tablets of bismuth subsalicylate four times daily for 4 weeks or bismuth combined with 2 weeks of 300 mg clindamycin four times daily. Clinical symptoms were recorded before and after treatment by means of visual analog scales. Patients in both treatment arms showed improvement in clinical scores for abdominal pain, heartburn, and gas or bloating. Microbiologic cure was achieved in only 1 of 11 patients treated with bismuth alone and in none of 7 treated with bismuth/clindamycin. Successful eradication of H. pylori may require combination of multiple antibiotics, as recommended at the IXth World Congress of Gastroenterology, or pharmacokinetic modulators such as H2-blockers or omeprazole. PMID- 1502491 TI - Diagnosis of bacterial overgrowth after culturing proximal small-bowel aspirate obtained during routine upper gastrointestinal endoscopy. AB - The purpose of this study was to evaluate the method of obtaining aspirated fluid for culture from the small intestine through a fiberoptic gastrointestinal endoscope for diagnosing small-bowel overgrowth. The study population consisted of 10 healthy volunteers and 26 patients with various gastrointestinal problems referred for routine endoscopic examination. The material to be cultured was obtained under direct visualization approximately 25 to 30 cm distal to the pylorus or from the afferent loop (in Billroth-II patients) with a sterilized sheathed wash pipe passed through the suction channel of the endoscope. Cultures were considered positive for bacterial overgrowth if total counts of organisms were 10(5)/ml or more. All healthy volunteers and 16 of 21 unoperated patients had sterile or insignificant growth, whereas all 5 patients who had Billroth-II operations had positive overgrowth. The endoscopic method for collection of proximal gastrointestinal fluid for culture is simple and can be performed during routine endoscopy. PMID- 1502492 TI - The Nobel Lectures in Immunology. The Nobel Prize for Physiology or Medicine, 1980. The major histocompatibility complex in man. Past, present, and future concepts. PMID- 1502493 TI - C3bi/CR3 is a main ligand-receptor interaction in attachment and phagocytosis of C3-coated particles by mouse peritoneal macrophages. AB - We investigated the relative role of C3bi-CR3 interaction in the binding and phagocytosis of EAC43 by mouse peritoneal macrophages. Anti-Mac-1 F(ab')2 markedly inhibited the binding and lymphokine-induced phagocytosis of both EAC43b and EAC43bi. Fifty per cent inhibition of attachment and phagocytosis occurred at 1 microgram/ml of anti-Mac-1 F(ab')2 in the incubation media. On the other hand, EIgG binding and phagocytosis were not inhibited at all even at a concentration of 10 micrograms/ml. Depletion of divalent cations from the incubation media abolished EAC43b and EAC43bi rosettes but not EIgG rosettes or phagocytosis. These data suggested that both EAC43b and EAC43bi binding to macrophages were mediated via CR3. Because a drastic decrease of EAC43bi rosettes was observed in the case of EAC43bi cells prepared with smaller amounts of C3, a small contamination of C3bi molecules on EAC43b, itself, cannot explain the efficient attachment of EAC43b. We propose that EAC43b on the macrophage surface can be quickly converted to EAC43bi, forming EAC43bi rosettes, and that those erythrocytes are vigorously ingested by lymphokine-activated macrophages. In accordance with this hypothesis, we demonstrated that EAC43b was converted to EAC43bi in the medium in which macrophages had been incubated. PMID- 1502494 TI - Enhancement of the antibody response to protein antigens by specific IgG under different experimental conditions. AB - Specific stimulation of the antibody response to protein antigens by IgG antibodies was studied in vivo. The response to TNP-coupled keyhole limpet haemocyanin (KLH-TNP) was enhanced by a TNP-specific IgG monoclonal antibody, 7B4, as measured both in ELISA (enzyme-linked immunosorbent assay) and by ELISPOT (enzyme-linked immunospot) method. Enhancement was seen when using both high and low doses of antigen and antibody. The antibody response to TNP-coupled bovine serum albumin (BSA-TNP), but not to TNP-coupled ovalbumin (OA-TNP), tetanus toxoid (TT-TNP) or diphtheria toxoid (DT-TNP), was also efficiently augmented by 7B4. Enhancement was seen when using both high and low coupling ratio of TNP to KLH. The fact that IgG-mediated enhancement is seen under many different experimental conditions suggests that it is a physiologically relevant phenomenon. In order to enhance the response to KLH-TNP and BSA-TNP, 7B4 had to be injected while antigen was circulating in blood. This supports that IgG mediated stimulation acts by concentrating circulating antigen into lymphoid centres. PMID- 1502495 TI - Involvement of the avian mu heavy chain in recolonization of the bursa of Fabricius. AB - In the chicken, the B cells develop in a specialized organ, the bursa of Fabricius. Earlier it was shown that neonatal bursal cells treated with polyclonal anti-chicken immunoglobulin antibodies are not able to recolonize the bursa when transferred into cyclophosphamide-treated chicks. In this study, 4-day old bursal cells were treated with different polyclonal and monoclonal anti immunoglobulin antibodies and transferred into 4-day-old cyclophosphamide-treated chickens. Two monoclonal anti-chicken IgM antibodies, CVI-59.7 and 21-2B2, recognizing distinct epitopes of the mu heavy chain, were inhibitory. Incubation of cells with 21-2B2 antibody caused about 90% inhibition of bursal recolonization. After incubation with CVI-59.7 antibody the inhibition was 50%. The high inhibition by 21-2B2 antibody was also seen when F(ab')2 fragments of the antibody were used. These results suggest that the entry of the cells needed for bursal recolonization is inhibited almost totally by 21-2B2 antibody, or that this antibody blocks further proliferation of the cells in bursal follicles. In conclusion, we have shown that a mu heavy chain epitope is intimately involved in the recolonization of bursal follicles, and distinct epitopes of the mu heavy chain are not equally important in this process. PMID- 1502496 TI - Aberrations in titre and avidity of serum IgM and IgG antibodies to microbial and food antigens in IgA deficiency. AB - The antibody levels and relative avidity of serum IgM and IgG antibodies against E. coli O antigens, poliovirus type 1 and beta-lactoglobulin were determined with enzyme-linked immunosorbent techniques in IgA deficient (IgAd) patients with frequent respiratory tract infections and healthy IgAd individuals. Healthy individuals with normal immunoglobulin levels served as controls. The IgM antibody levels against the bacterial, viral and food antigens and the IgG antibody levels against the bacterial antigens were significantly higher in the IgAd group with recurrent infections than in the group of healthy IgAd individuals. The symptomatic IgAd group had significantly higher levels of the IgG antibodies against the bacterial antigen, also when compared with controls. In contrast the healthy IgAd individuals had the highest avidities of IgM antibodies to the viral and food antigens. The high avidities of antibodies could be a compensatory host defence mechanism in IgAd. These aberrations may appear as a consequence of increased mucosal exposure in IgAd to antigens such as E. coli or beta-lactoglobulin, but presumably not to poliovirus which is only exceptionally present in the milieux. They could also be a result of the previously suggested dysregulation of antibody responses in IgAd. PMID- 1502497 TI - Hydrocortisone treatment of BCG-infected mice impairs the activation and enhancement of antimicrobial activity of peritoneal macrophages. AB - The present study concerns the effect of hydrocortisone (HC) on the effector functions of Bacillus Calmette Guerin-purified protein derivative (BCG-PPD) activated macrophages. Such activated macrophages release greater amounts of H2O2 and NO2-, inhibit the intracellular proliferation of T. gondii and kill L. monocytogenes more efficiently than resident macrophages. This activation was not fully expressed by macrophages from BCG-activated mice that had received a subcutaneous injection of HC 2 days before intraperitoneal injection of PPD, since the inhibition of the intracellular proliferation of T. gondii, the release of NO2- and the rate of intracellular killing of L. monocytogenes were lower than in macrophages from BCG-PPD-activated mice. However, treatment with HC did not impair the release of H2O2 by BCG-PPD-activated macrophages. The results show that the treatment of infected mice with HC inhibits their ability to develop adequate intracellular microbicidal mechanisms. PMID- 1502498 TI - A family of cross-reacting proteins secreted by Mycobacterium tuberculosis. AB - Cross-reactions between five proteins actively secreted by Mycobacterium tuberculosis were studied by crossed immunoelectrophoresis, SDS-PAGE with immunoblotting, and ELISA using polyclonal rabbit antisera and mouse monoclonal antibodies to the purified proteins. The monoclonal antibody HBT4 was demonstrated to react with the MPT51 protein. The 85A, 85B and 85C constituents of the M. tuberculosis and Mycobacterium bovis BCG antigen 85 complex cross-react extensively, each of the components containing component-specific as well as cross-reacting epitopes. These components also cross-reacted with MPT51 and MPT64. N-terminal sequence studies revealed striking homology at the amino acid level between 85A, 85B, 85C and MPT51. MPT64 showed less homology. In addition, striking homology was demonstrated between two different stretches within the 85B sequence and indicated between three stretches within the MPT64 molecule. Thus, a family of at least four secreted proteins with common structural features has been demonstrated in mycobacteria. MPT64 may also belong to this family. PMID- 1502499 TI - Analysis of HLA genotypes and susceptibility to insulin-dependent diabetes mellitus: HLA-DQ alpha complements HLA-DQ beta. AB - It is well known that certain genes in the HLA-D region confer increased susceptibility to insulin-dependent diabetes mellitus (IDDM). Previous studies have documented an increased risk associated with the HLA-DR beta chain alleles, DR3 and DR4, and the DQ beta chain allele DQB1*0302 (formerly DQw8). Since DQ alpha is also polymorphic and has been strongly implicated as the primary IDDM susceptibility locus in other races, we wanted to assess the contribution of DQ alpha to IDDM in Caucasians. This information would enable us to define more precisely the class II association with IDDM as well as gain insight into issues of cis versus trans association of DQ heterodimers in this disease. To this end, the DQ alpha genotype was determined for a large group of diabetic and normal Caucasian individuals who had been HLA-DQ beta and HLA-DR typed previously. Using the polymerase chain reaction and a set of twelve oligonucleotide probes, we determined the DQ alpha genotype of 323 patients with IDDM and 182 normal subjects. We found that certain DQ alpha alleles are decreased in the diabetic population compared with normal subjects (i.e. DQA1*0102 and *0103), while others are significantly increased in patients with IDDM (i.e. DQA1*0301 and *0501). In addition, certain combinations of DQ alpha alleles are associated with increased susceptibility to disease (i.e. DQA1*0301, *0501). These results parallel our findings at the DQ beta locus; however, because of the various associations between DQ alpha and DQ beta chains, the risks conferred by DQ alpha are generally lower than those at DQ beta. Moreover, our data indicate that, in Caucasians, no single DQ alpha allele accounts for the highest degree of susceptibility to IDDM as in other races, although DQ alpha analysis may be informative in a few cases. When done in combination, however, oligonucleotide analyses at both DQ alpha and DQ beta complement each other and provide a more complete assessment of the HLA-associated component of disease susceptibility in IDDM. PMID- 1502500 TI - Analysis of HLA genotypes and susceptibility to insulin-dependent diabetes mellitus: association maps telomeric to HLA-DP. AB - There is convincing evidence that certain combinations of alleles within the human leucocyte antigen (HLA) complex, particularly within HLA-DQ, are associated with either resistance or susceptibility to insulin-dependent diabetes mellitus (IDDM). A previous study conducted on a large, well-defined group of patients demonstrated that DQB1*0302 (DQw8) conferred 'dominant susceptibility' to IDDM while DQB1*0602 (DQw1.2) conferred 'dominant protection'. The availability of this population enabled us to further assess susceptibility associated with other class II alleles in an effort to map an outside HLA boundary of disease association. Using a group-specific polymerase chain reaction protocol and a series of oligonucleotide probes which define over twenty DP beta alleles, we studied 286 unrelated Caucasian patients with IDDM and 184 normal subjects. We found that while several alleles are increased (DPB1*0201, DPB1*0301, DPB1*0402) or decreased (DPB1*0101, DPB1*0202) in the diabetic population compared with the normal subjects, the HLA association with IDDM is considerably weaker at the DP locus. These data define the centromeric boundary for the HLA-associated susceptibility gene in IDDM, localizing susceptibility to the region telomeric to HLA-DP up to and including HLA-DQ. PMID- 1502501 TI - Peptide binding to class I molecules of the major histocompatibility complex on the surface of living target cells. AB - Molecules encoded by the class I major histocompatibility genes bind short (nonameric) peptides produced by intracellular proteolysis of antigens. These complexes formed intracellularly are then expressed on membranes of target cells and recognized by the antigen receptor of cytolytic T cells. No binding of externally added peptides could so far be monitored directly on the antigen presenting cells, although cytotoxicity experiments and indirect binding assays provided evidence for its existence. Here we report experiments where specific binding to class I molecules, of externally added peptides, has been monitored on living cells. N-terminal biotin-labelled Kd-restricted peptides (residues 147 155, residues 147-158, and an analogue lacking the arginine at position 156, derived from the sequence of the influenza A virus nucleoprotein) were incubated with murine H-2Kd mastocytoma cells (line P815) at 4 degrees C. The binding on surface of live, intact cells was then demonstrated fluorometrically via the interaction of a streptavidin-phycoerythrin conjugate with the biotin-labelled peptides. Thus, this binding does not involve processing, and its specificity in terms of peptide structure was established by competition with the respective unmodified peptides. The specificity of binding to class I molecules was demonstrated by blocking experiments using monoclonal antibodies specific for H 2Kd. Finally, a correlation was observed between the results of peptide binding measurements and those of cytotoxicity assays. PMID- 1502503 TI - [Elbow dysplasia in the dog]. AB - Elbow dysplasia (ED) is a common developmental malformation in many breeds over 20 kg bodyweight. It may affect as many as 50% of all dogs within a breed. Arthrosis and poor performance may result. The most common forms of ED are fragmented medial coronoid process, osteochondrosis of the medial humeral condyle and loose anconeal process. There is evidence for the existence of a hereditary disposition for osteochondrosis in Labrador retrievers. In Sweden selection of ED free dogs for breeding resulted in reduction of frequency and degree of severity of ED in the offspring. Adoption of a similar breeding program for Switzerland is suggested. PMID- 1502502 TI - Nucleotide sequence analysis of rheumatoid factors and polyreactive antibodies derived from patients with rheumatoid arthritis reveals diverse use of VH and VL gene segments and extensive variability in CDR-3. AB - The heavy and light chain nucleotide sequences of 17 monoreactive and polyreactive rheumatoid factors largely derived from the inflamed synovial tissue of two patients with rheumatoid arthritis are described. Some of these sequences have been the subject of a previous report from our laboratories. Additionally, a few rheumatoid factors from the peripheral blood of patients with systemic lupus erythematosus and Sjogren's syndrome as well as a normal individual are included. A review of our previous results as well as the new data provided within this paper lead to the following major conclusions: (1) Rheumatoid factors and polyreactive antibodies derive from a diverse array of VH and VL gene segments; (2) While many rheumatoid factors and polyreactive antibodies are direct or nearly direct copies of germline genes, some show clear evidence of somatic mutation; (3) The CDR3 of all of these antibodies is extraordinarily diverse in length and composition. Certain 'restrictions' do appear in this very large sample: (a) the polyreactive antibodies are exclusively lambda, and (b) there seems to be a preponderance of a particular subset of VH3 genes beyond that one would expect based on random utilization. PMID- 1502504 TI - [What is your diagnosis? Which treatment do you suggest?]. PMID- 1502505 TI - Piecemeal patents. PMID- 1502507 TI - Compulsive canines. PMID- 1502506 TI - Galling the bears. PMID- 1502508 TI - DNA fingerprinting reconsidered (again) PMID- 1502509 TI - Defining dyslexia. PMID- 1502510 TI - G proteins. PMID- 1502511 TI - Breath tests in medicine. PMID- 1502512 TI - Reproductive strategies of frogs. PMID- 1502513 TI - Working memory and the mind. PMID- 1502514 TI - Major disorders of mind and brain. PMID- 1502515 TI - Aging brain, aging mind. PMID- 1502516 TI - How neural networks learn from experience. PMID- 1502517 TI - The problem of consciousness. PMID- 1502519 TI - See-through view. Virtual reality may guide physicians' hands. PMID- 1502518 TI - The hole story. Fine-pore membranes remove viruses from biological drugs. PMID- 1502520 TI - Noisy nucleotides. DNA sequences show fractal correlations. PMID- 1502521 TI - Population pressure. The road from Rio is paved with factions. PMID- 1502522 TI - Mind and brain. PMID- 1502523 TI - Mind and brain. PMID- 1502524 TI - The developing brain. PMID- 1502526 TI - The biological basis of learning and individuality. PMID- 1502525 TI - The visual image in mind and brain. PMID- 1502527 TI - Brain and language. PMID- 1502529 TI - [Sonography in salmonella enterocolitis]. AB - 27 patients suffering from salmonella enterocolitis--24 proven by stool cultures, 3 confirmed serologically--were examined for ultrasound findings. In 81% the left side gut wall was concentrically thickened up to 7 mm (5-11). Further sonographic findings were: Less demarcated gut wall layers in 33%, hypoechoic gut wall in 48%, polypoid mucosa thickening in 33%. In individual cases enlarged mesenteric lymph nodes, splenomegaly, and ascites were seen. Sonographic changes correlated well with clinical results in respect of the intensity of the illness. PMID- 1502528 TI - [Abdominal sonography in primary diagnosis of blunt abdominal trauma]. AB - 200 patients with blunt abdominal trauma were scanned by ultrasound primarily. 152 showed a normal sonographic examination. In 24 patients an organic injury was visualised. These 20 splenic injuries, 2 lesions of the kidney, 1 splenic and renal lesion and 1 hepatic and splenic rupture were confirmed by CT in 9 cases, by laparotomy in 9 cases, by sonographic follow-up in 2 cases. 23 patients showed an intraabdominal fluid collection, in 16 patients a decrease was seen by ultrasound. 7 patients were directly operated on because of a visible increase of intraabdominal fluid. The lesions consisted of 3 hepatic ruptures, 2 retroperitoneal bleedings. Ultrasound is a reliable tool in the diagnosis of blunt abdominal trauma on the day of admittance and in the evaluation of injuries in respect of operative or conservative management. PMID- 1502530 TI - [Sonography of pancreatic cancer]. AB - The aim of this retrospective study was to test the quality of pancreatic sonography in a hospital without CT. Out of 25 patients 21 were assessable. We made the correct diagnosis in 76.2% (n = 16) of the cases. The tumour size was between 25 and 60 mm. 20 tumours showed a relatively hypoechoic mass. A dilatation of biliary ducts could be seen in 87.5%. Metastasis of lymph nodes we could only detect in 38.5%, liver metastases in 64.5%. The sensitivity increases with the experience of the examiner, but lot of time is necessary. It is difficult to make a differential diagnosis between carcinoma and pancreatitis. In this cases, CT shows better results. In spite of improvements in sonography, early cancer still is a diagnostic problem. PMID- 1502531 TI - [Cryptogenetic ascites. Attempts at original pathophysiologic explanation of a monomorphic sonographic image pattern]. AB - In 15,645 consecutive ultrasound examinations of the abdomen (1986 to 1988), free fluid in the peritoneal cavity was found in 247 patients by internal trial during 397 sessions (= 2.5%). Most frequent basic diagnosis for the reason of this symptom were tumorous diseases (99 patients corresponding to 40.1%), cirrhosis of the liver (52 patients corresp. to 22.1%) and heart failure (31 patients corresp. to 12.6%, among these complex gayprooft myocardial insufficiency 24, right heart failure 7). Ovarian cysts or cystomas (7), acute/chronic-recurrent pancreatitis (6), Crohn's disease (3), infections (3), rheumatoid disorders (3), nephrotic syndrome (2), and extra-uterine pregnancy (2) were more rarely represented. In 23 patients (corresp. to 9.3%) the cause of an ascites remained obscure. Among these, a high prevalence of the female sex in the premenopausal age was remarkable with a score of 20:3 (statistically significant difference in terms of the other patients of our group). This observation suggests that an ovarian factor plays a role in the development of ascites in the absence of other evident causes. The literature implies that endometriosis is rather prominent, followed by oligosymptomatic infections or inflammatory diseases. PMID- 1502532 TI - [Representation of texture parameters of B-mode sonograms in image form]. AB - The possibility is exemplified of visualising important parameters of the statistical texture describing the echogenicity of ultrasound B-mode scans of the liver as a composite image. The two relevant parameters are gray level and standard deviation of gray levels. These were selected because they offer the best criterion to differentiate between tissues. In a composite image, the mean gray level is represented by the luminosity information, whereas the other main parameter of the gray-level histogram, the standard deviation of gray levels, is represented by the colour information. These composite images show texture parameters of the whole scan and allow an efficient documentation of the same. PMID- 1502534 TI - [B-scan ultrasound findings in the carotid bifurcation area of hemodialysis patients]. AB - Using B-mode ultrasonography, the frequency of carotid atherosclerosis was investigated prospectively in 50 patients on maintenance haemodialysis compared to healthy controls. The patients showed significantly more atheromatous plaques at the carotid bifurcation, as well in the internal and external carotid artery (chi-square-test, p less than 0.05). There was no statistical difference between normotensive patients on haemodialysis and the control group, but hypertensive patients showed statistically significant more plaques of the cervical vessels (chi-square-test, p less than 0.05). Therefore, atheromatous plaques in haemodialysis patients appear to be due to hypertension rather than to maintenance dialysis. PMID- 1502533 TI - [Sonographic evaluation of changes in testicular tissue by ultrasound spectroscopy]. AB - Experimental investigations were carried out under in vitro conditions on 25 normal human testicular specimens and on 60 pathological testicular specimens to ascertain the ultrasound attenuation using an ultrasound spectroscopic measuring technique. The ultrasound attenuation was established by calculating the ultrasound attenuation coefficient alpha. The average values of ultrasound attenuation (alpha) in normal testicular tissue were distinctly lower than in pathologically altered testicular specimens. A comparison of the various pathologically altered testes showed higher attenuation in the case of malignant neoplasms whilst the highest average values of wore recorded for non-neoplastic pathological alterations in the testicular tissue. The results of the investigations show that certain alterations in the tissue can be ascertained by ultrasound spectroscopy. The analysis of further acoustic parameters in future investigations, such as ultrasound back-scattering and velocity, along with the recording of ultrasound attenuation, gives scope for improved assessment of the tissue. Thus ultrasound spectroscopy increases the sonographic accuracy acquired through analysis and the weighing up of symptoms of tissue dependent ultrasound parameters. PMID- 1502535 TI - [Possibilities and limits of biplane transesophageal echocardiography in dissection of the thoracic aorta]. AB - Dissecting aneurysms of the thoracic aorta can be rapidly and accurately diagnosed by transoesophageal echocardiography. The recent advent of the transoesophageal echocardiographic probe with transverse and longitudinal imaging transducers that add orthogonal viewing planes is an important advance in the evaluation of both the anatomic and haemodynamic status of the patient. It allows a still better understanding of the pathologic changes and therefore helps in surgical decision making. With the capabilities of colour flow Doppler, biplane transoesophageal echocardiography proves to be an ideal tool for the preoperative confirmation of the suspected diagnosis, intraoperative assessment and post operative ambulatory follow-up and should be applied whenever possible. PMID- 1502536 TI - [Hypogangliosis of the sigmoid colon: possibilities of sonographic diagnosis]. AB - This case report concerns a 53-year old woman suffering from recurrent spastic pain and a painful "resistance" in the left lower bowel for the last 30 years. Earlier clinical investigations including endoscopy and laparoscopy did not yield any results. In a recent investigation, only sonography showed wall thickening and an echo-poor wall pattern of the sigmoid colon indicating this to be the site of painful resistance. Resection of the sigmoid colon was performed. Histologically a slight hypogangliosis of the colon and muscular hypertrophy were detected (as the only pathological signs). The patient was free from symptoms since operation. This case report proves that ultrasound may yield pointers (or confirm the diagnosis) in unclear abdominal diseases. PMID- 1502537 TI - [Functional colonic pain. An important clinical and sonographic differential diagnosis]. AB - Functional abdominal pain may often be sonographically attributed to the colon. Typically a segment of the colon is painful at direct palpation, but the wall is not thickened. The contractions between the haustra are often marked. The haustra are clearly outlined and cast acoustic shadows. If the patient also experiences spontaneous pain in this region, functional colonic pain, explained as spasms of the muscle coat, may be assumed. Clinically there are often other symptoms of the irritable bowel disease or a spastic constipation. In daily practice functional colonic pain is as frequent as dyspepsia. Differential diagnosis includes intestinal (peptic ulcer, Crohn's disease, appendicitis, diverticulitis, colon cancer) and extraintestinal diseases (e.g. of the gallbladder, pancreas and female adnexes). PMID- 1502538 TI - [When is ultrasound damaging?]. PMID- 1502539 TI - [Comments on U. Kroschel et al.: Sonographic imaging of pulmonary embolisms- results of a prospective study]. PMID- 1502540 TI - [Sonomorphology of stress cholecystitis]. AB - Acute acalculous cholecystitis is a well-known complication in postoperative and particularly in severely traumatized unit patients. All that is known so far of "stress"-cholecystitis is based on episodic case reports and retrospective analyses. An incidence between 0.5 and 4.2%, a complicated clinical course and a lethality up to 75% have been reported. In intensive-care unit patients a clinical diagnosis of suspected acute cholecystitis is rarely reliable; greater reliance is placed on the ultrasound findings as seen in our prospective study. According to the literature, the established ultrasound criteria of cholecystitis include: hydrops, thickening of the gallbladder wall, sludge, subserosal oedema, pericholecystic fluid collection and fragmentation of the gallbladder wall. Other factors, however, may also lead to morphological changes of the gallbladder, and hence there is no agreement about the definitive sonomorphology of this entity. The variability of sonomorphological criteria is reviewed and compared to the results of a series of our own. PMID- 1502542 TI - Medicine and life. PMID- 1502541 TI - On the consensus for primary care: reflections on the First National Primary Care Conference. PMID- 1502543 TI - Human genome project. AB - Genome n. [gene plus chromosome] the complete set of chromosomes containing all of the genes of an organism. For man this set of 46 per cell stretches to a 6 foot strand of DNA. Within this string of 3 billion nucleotide bases are 100,000 genes. Utilizing a 4 letter alphabet (Adenine, Guanine, Cytosine, Thymine), genes provide the blueprint for the amino acid sequence of structural protein (cell membrane, connective tissue, etc) or functional protein (hormones, enzymes, transmitters, etc). DNA replication guarantees exact gene copies and chromosome meiosis and crossing over guarantees varied gene combinations. This forms the basis for the similarity and the diversity of all of humankind: the similarity needed to perpetuate successful genes and the diversity needed for genes to respond to the weeding out process of evolution. PMID- 1502544 TI - Science is great, but scientists are still people. PMID- 1502545 TI - Condom use. PMID- 1502546 TI - NSF and duplicate grant submissions. PMID- 1502547 TI - Combating epidemic cholera. PMID- 1502548 TI - Fetal transplants show promise. PMID- 1502549 TI - The tissue bank's shaky underpinnings. PMID- 1502550 TI - NSF holds plan close to its vest. PMID- 1502551 TI - Mitochondrial Eve: wounded, but not dead yet. PMID- 1502553 TI - A new dimension in AIDS research. PMID- 1502552 TI - Bush Administration weighs in on AIDS. PMID- 1502554 TI - Getting some "backbone": how MHC binds peptides. PMID- 1502555 TI - Science innovation '92: the San Francisco sequel. PMID- 1502556 TI - Genes, patents, and product development. AB - In the past year, the National Institutes of Health (NIH) has filed patent applications on more than 2750 partial complementary DNA sequences of unknown function. The rationale for the filings--that patent protection may be necessary to ensure that private firms are willing to invest in developing related products -rests on two premises: first, that NIH may obtain patent rights that will offer effective product monopolies to licensee firms, and second, that unless NIH obtains these rights now, firms will be unable to obtain a comparable degree of exclusivity by other means, such as by obtaining patents on their own subsequent innovations. Neither premise is clearly wrong, although both are subject to doubt in view of statements from industry representatives that the NIH patenting strategy will deter rather than promote product development. PMID- 1502557 TI - Genome research: fulfilling the public's expectations for knowledge and commercialization. AB - This article provides a historical perspective for the patenting of gene sequences and describes the fundamentals and evolution of patent law. It summarizes federal technology transfer law and policy and assesses the impacts of patenting on academic research. The patentability of gene sequences is then considered along with potential impacts that published sequence data may have on obtaining patent protection for downstream products. Industry's position on gene patenting is summarized and perspectives from the emerging public record on these issues are presented. The article discussing points at which the filing of patent applications and the licensing of patents may be appropriate. It concludes that technology transfer policies for genome research must be adopted carefully so that they remain viable in a time of rapid technological change. PMID- 1502558 TI - Patents on random complementary DNA fragments? AB - The proposal by the National Institutes of Health (NIH) to patent products resulting merely from sequencing the human genome is a mistake: at worst, it is wrong in patent law; at best, it relies on deficiencies in law concerning what is "useful" as a requirement for patents. The proposal is symptomatic of a problem besieging biotechnology--attempts to control the raw material of scientific experimentation before research has determined the practical value of such material--that needs curing on many fronts. Corrective measures are proposed for adoption by the Executive branch, the Congress, and the courts. PMID- 1502559 TI - Internal stark effect measurement of the electric field at the amino terminus of an alpha helix. AB - The strengths of electrostatic interactions in biological molecules are difficult to calculate or predict because they occur in complicated, inhomogeneous environments. The electric field at the amino terminus of an alpha helix in water has been determined by measuring the shift in the absorption band for a covalently attached, neutral probe molecule with an electric dipole moment difference between the ground and excited electronic states (an internal Stark effect). The field at the interface between the helix and the solvent is found to be an order of magnitude stronger than expected from the dielectric properties of bulk water. Furthermore, although the total electric dipole moment of the helix increases with length, the electric field at the amino terminus does not. PMID- 1502560 TI - Pseudo--half-knot formation with RNA. AB - A pseudo--half-knot can be formed by binding an oligonucleotide asymmetrically to an RNA hairpin loop. This binding motif was used to target the human immunodeficiency virus TAR element, an important viral RNA structure that is the receptor for Tat, the major viral transactivator protein. Oligonucleotides complementary to different halves of the TAR structure bound with greater affinity than molecules designed to bind symmetrically around the hairpin. The pseudo--half-knot--forming oligonucleotides altered the TAR structure so that specific recognition and binding of a Tat-derived peptide was disrupted. This general binding motif may be used to disrupt the structure of regulatory RNA hairpins. PMID- 1502561 TI - Combining experimental information from crystal and solution studies: joint X-ray and NMR refinement. AB - Joint refinement of macromolecules against crystallographic and nuclear magnetic resonance (NMR) observations is presented as a way of combining experimental information from the two methods. The model of interleukin-1 beta derived by the joint x-ray and NMR refinement is shown to be consistent with the experimental observations of both methods and to have crystallographic R value and geometrical parameters that are of the same quality as or better than those of models obtained by conventional crystallographic studies. The few NMR observations that are violated by the model serve as an indicator for genuine differences between the crystal and solution structures. The joint x-ray-NMR refinement can resolve structural ambiguities encountered in studies of multidomain proteins, in which low- to medium-resolution diffraction data can be complemented by higher resolution NMR data obtained for the individual domains. PMID- 1502562 TI - Mechanisms of action of cyclosporine and effects on connective tissues. AB - Cyclosporine is a potent immunomodulatory agent with an increasing number of clinical applications. Its major mode of action is inhibition of the production of cytokines involved in the regulation of T-cell activation. In particular, cyclosporine inhibits the transcription of interleukin 2. Although cyclosporine's major actions are on T cells, there is some evidence that it produces direct effects on other cell types. Its immunosuppressive action is closely linked to its binding of cyclophilin, a member of a family of high-affinity cyclosporine binding proteins widely distributed in different cell types and in different species. The cyclophilins have been shown to have peptidyl-prolyl cis-trans isomerase enzyme activity that is blocked by cyclosporine. Although this may be a factor in cyclosporine's selective inhibition of cytokine gene transcription, it is still unclear whether inhibition of this activity is the mechanism through which cyclosporine exerts its effects on target cells. The ubiquitous presence of cyclophilins raises the question of why cyclosporine has major effects on T cells. Perhaps the critical proteins affected are transcriptional regulators restricted in their tissue distribution. The effects of cyclosporine on T cells and, directly or indirectly, on connective tissue cells, all of which can produce a range of cytokines, are of interest in relation to the tissue changes that occur in such inflammatory conditions as rheumatoid arthritis. PMID- 1502563 TI - The paradox of effective therapies but poor long-term outcomes in rheumatoid arthritis. AB - Treatment of rheumatoid arthritis (RA) presents a paradox: Many effective therapies are extensively documented in numerous clinical trials, but all long term studies from clinical settings indicate that most patients with RA have progressive disease. This paradox may be explained in part on the basis of four observations: (1) Results of therapies for RA have been evaluated primarily according to clinical trials over short periods rather than according to long term clinical observations over many years; (2) increased mortality rates in RA have not been widely recognized because RA is not included on death certificates of more than half of the patients who die with this disease; (3) mortality in RA generally has been attributed to causes unrelated to RA or to drug toxicity, but higher mortality in specific patients is predicted primarily by more severe clinical status; and (4) published reports indicating an optimistic prognosis in RA have been based on epidemiological studies rather than on patients in clinical settings. In epidemiological studies of large populations, 75% of individuals who meet the 1958 American Rheumatism Association (ARA) criteria for RA have no evidence of disease 3 to 5 years later; in contrast, in clinical settings more than 90% of patients with RA have evidence of disease 3 to 5 years later, generally with progression. PMID- 1502564 TI - Prevention of adjuvant arthritis by cyclosporine in rats. AB - The effect of cyclosporine A during the development phase of adjuvant arthritis was studied in 40 female rats. Five groups of eight animals each received oral cyclosporine, 2.5, 5, 10, 20, or 30 mg/kg daily for 30 days. Also, eight normal and eight diseased rats served as placebo controls. At the time of inoculation of the adjuvant suspension on day 0, measurement of disease parameters (paw swelling and vertebral density) was started concomitantly with beginning of therapy. On completion of the study, the animals were killed, and after measurement of total skeletal and segmental (hind legs and caudal spine plus two caudal vertebrae) calcium, the two assessed vertebrae and both femoral condyles were removed for histomorphometric evaluation (vertebrae) and for estimation of glycosaminoglycan (GAG) content of cartilage. Blood for osteocalcin determinations also was taken at term from control and untreated arthritic rats and from animals that had received 10 mg/kg cyclosporine. Treatment with 2.5 mg/kg was ineffective, but doses between 5 and 20 mg/kg prevented the development of articular and osseous lesions. The 20 mg/kg dose showed no better effect than 10 mg/kg. This was shown by the absence of inflammation and the presence of normal condylar GAG and total mineral content in the areas screened. Untreated animals showed marked reductions in all of these parameters. The 30 mg/kg dose was effective in blocking the GAG loss, but significant reductions in bone density and trabecular volume were seen. There was a close correlation between GAG and bone density values, suggesting a common causal relationship. Circulating osteocalcin was significantly elevated in the untreated animals with adjuvant arthritis.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1502565 TI - Cyclosporine in rheumatoid arthritis: documented efficacy and safety. AB - The experience from eight open studies and five controlled trials of cyclosporine in rheumatoid arthritis is reviewed. A therapeutic approach characterized by low initial doses and slow upward titration appears to minimize the toxicity while retaining sufficient amounts of the efficacy seen with higher doses, although the onset of benefit is slower. In short-term studies, renal dysfunction and other side effects appear to be reversible. However, studies of combinations of cyclosporine and other slow-acting agents, long-term studies, and more renal biopsy specimens are needed to determine the appropriate use of this agent. Cyclosporine holds promise as an important addition to the therapeutic armamentarium for patients with rheumatoid arthritis. PMID- 1502566 TI - Cyclosporine in rheumatoid arthritis: beyond experimentation. AB - The potential for combined therapy in rheumatoid arthritis is rapidly increasing considering the recent development of various new treatment modalities. However, an aggressive effort must be made to stage patients according to various clinical and immunological parameters. Only then can appropriate combined therapy be used effectively in this disease process. The development of such combined therapy could expand into other diseases such as scleroderma, systemic lupus erythematosus, and multiple sclerosis. PMID- 1502567 TI - Cyclosporine: nephrotoxic effects and guidelines for safe use in patients with rheumatoid arthritis. AB - Renal abnormalities occur frequently in patients with rheumatoid arthritis; they may be complications of the rheumatoid disease process itself (amyloidosis) or may result from various therapies including gold compounds, D-penicillamine, analgesics such as aspirin or phenacetin used long term, and nonsteroidal anti inflammatory drugs. Cyclosporine, a highly effective immunosuppressive agent currently under investigation as a treatment for RA, is also known to produce renal dysfunction. Some forms of functional and structural tubular changes appear readily reversible. Others associated with renal vasculopathy and interstitial fibrosis can lead to irreversible nephrotoxicity. A clear understanding of the pharmacology, drug interactions, and types of renal side effects encountered with cyclosporine can lead to a reduction of adverse renal reactions. Similarly, an understanding of which patients are at high risk for renal dysfunction can lead to safer and more efficacious use of this potent immunosuppressive agent. PMID- 1502568 TI - [The effect of various sterilization procedures on the osteoinductive properties of demineralized bone matrix]. AB - To minimize potential infection following the transplantation of allogeneic bone, extremely rigorous selection of donors and careful processing and storage of samples are required. Other major problems related to allogeneic transplants, such as reduced osteogenic properties and immunological reactions, led to the development of demineralized bone matrix (DBM). This osteoinductive bone extract is largely free of antigens and is easy to produce. However, to eliminate the potential risk of infection, DBM should be sterilized prior to implantation. The purpose of this study was to investigate the influence of different sterilization techniques on the osteoinductive properties of DBM. A series of 76 cortical defects (drill holes) 0.6 cm in diameter in the tibiae of 11 Merino sheep were filled with DBM in addition to autogeneic and allogeneic cancellous bone. Prior to implantation DBM was sterilized by autoclaving, gamma irradiation, or application of ethylene oxide or ethyl alcohol. A further 12 drill holes were left empty as controls. The formation of new bone was examined 3 and 6 weeks postoperatively, using histological, fluorescent-optical and microradiographical techniques. The amount of newly formed bone was also quantified. Apart from autoclaved DBM all matrix grafts showed excellent new bone formation following sterilization, by far exceeding the formation with allogeneic cancellous bone. PMID- 1502569 TI - [Standardized ultrasound study with computer-assisted documentation of findings in diagnosis of polytrauma patients]. AB - Based on the results of a prospective trial to establish the value of routine ultrasound examination in cases of polytrauma or blunt abdominal trauma, we report on our standard ultrasound examination and computer assisted documentation of the findings. Between May 1988 and December 1990 we examined 233 patients with polytrauma or blunt abdominal trauma. The results were compared with those of abdominal lavage (n = 47) performed during the same period. We found a sensitivity of 100% and a specificity of 99.5% for the ultrasound findings and a sensitivity of 80% and a specificity of 100% for the abdominal lavage. We conclude that ultrasonography should be the first diagnostic procedure used in the emergency room in cases of polytrauma and blunt abdominal trauma. PMID- 1502570 TI - [The problem of the closed abdominal injury in polytrauma patients]. AB - The histories of 66 patients with blunt abdominal trauma requiring surgery in the period from 1985 to 1989 were analysed. The patients were divided into three groups on the basis of the other injuries present. Group I, isolated blunt abdominal trauma and blunt abdominal trauma with slight concomitant injuries (18 patients, ISS 17.17 +/- 1.40); group II, blunt abdominal trauma with severe concomitant injuries but without craniocerebral trauma (23 patients, ISS 29.34 +/ 1.45); and group III, blunt abdominal trauma with severe concomitant injuries and an additional craniocerebral trauma (25 patients, ISS 31.08 +/- 1.27, GCS: 10.04 +/- 0.88). Initially, the diagnosis was made in 23 cases by means of diagnostic peritoneal lavage and in 43 cases by means of sonography. The subsequent laparotomy revealed the ultrasound findings to have been false positive in 3 cases. No false-negative ultrasound findings were demonstrated at all. Peritoneal lavage, on the other hand, was found to have yielded false negative and false-positive findings in 2 cases each. Counting from the time of admission, the time up to diagnosis of the intra-abdominal injury was 85 +/- 14.3 min in group I, 82 +/- 9.9 min in group II, and 86 +/- 12.9 min in group III. Thus, the presence of severe additional injuries did not lead to any significant delay in the diagnosis of blunt abdominal injury requiring surgery. The total mortality rate was 18.18% (group I, 11.1%; group II, 21.7%; group III, 20.0%). Six patients died in the acute phase and a further six patients during their stay on the intensive care ward. PMID- 1502571 TI - [Hyperextension somersault trauma]. AB - Neurological failure can occur as one feature of hyperextension trauma of the cervical spine. Apart from predisposing factors, such as dorsal osteophytes and congenital spinal stenosis, an acute narrowing of the spinal canal caused by a hyperextension somersault trauma can cause such a trauma. We observed three cases of paraplegic syndrome resulting from hyperextension somersault trauma of the cervical spine. Fast recovery from the symptoms within 12 h indicates vascular damage. The mechanism of the accident is shown with reference to clinical and experimental investigations. Hyperextension somersault trauma is characterized by a plunge from a low height, with the danger of somersaulting of the body and impact at the forehead while the head is retroflected. For this reason, extension treatment ought to be contraindicated if an accident of this kind has happened. Emphasis should be placed on adequate positioning of the patient. PMID- 1502572 TI - [Humerus reconstruction after gunshot fracture]. AB - High-velocity bullits can cause severe blast injuries with shattering and defects of the large bones. Initial external fixation is followed by rebuilding of the bone, which is difficult due to concomitant infection, poor revascularization and lack of a suitable bone bed. A case report of an injured African soldier shows the follow-up and difficulties of reconstruction of the shattered humerus by repeated spongious bone grafting. After successful remodeling of the bone, external fixation is followed by ASIF dynamic compression-plate osteosynthesis. PMID- 1502573 TI - [Technique and results of modified percutaneous bore wire osteosynthesis of the distal radius]. AB - A modified technique for percutaneous K-wire pinning of distal radius fractures is presented. With this method, three to four K-wires are introduced from the radial styloid process towards and through the dorsal, volar and ulnar proximal cortical wall, respectively. After the fracture fragments have been demonstrated to be stable, the wires are cut, bent over and fixed. Then a dorsal plaster splint is applied, which should be worn for 4-6 weeks, depending on whether or not there is a dorsal comminution zone. Fifty-five patients have been operated on by this method. At follow-up 6 months after the operation, no secondary dislocation, wire migration, infection, Sudeck syndrome or functional disturbance was seen. The advantage of this method is emphasized as compared with the usual, previously published method. PMID- 1502574 TI - [Injury of the palmar fibrocartilage of the proximal interphalangeal joint of the long finger. Treatment and results within the scope of follow-up]. AB - In 155 out of 389 patients with lesions of the fibrocartilage on the proximal interphalangeal (PIP) joint of the fingers, who were treated between January 1989 and 31 December 1989, a radiological and clinical follow-up was done after a mean interval of 1.5 years. In 82% a palmar lip fracture was diagnosed; the remaining 18% were attributed to a ligamentous lesion of the palmar fibrocartilate because of the clinical findings and negative X-ray results. Very good or good therapeutic results were achieved in 95%. Immobilization of the extended PIP joint for 2-3 weeks by a fingercast or plaster splint turned out to be the treatment of choice; surgical intervention was not indicated in any of these cases. PMID- 1502575 TI - [Reconstructive interventions of the posterior cruciate ligament--experimental studies of isometric aspects. Part I: Studies of a string model]. AB - In six intact cadaveric knees, we measured how the distance between six selected points in and around the femoral and tibial attachment area of the posterior cruciate ligament (PCL) changes with knee flexion. After complete removal of the PCL, 2-mm drill holes were made at the selected points. Each femoral point was measured against each tibial point using a heavy suture that was passed through the drill holes. The proximal end of the suture was fixed to the lateral aspect of the femur. The distal end of the suture was attached to a measuring unit. The changes in femorotibial distance were measured during flexion from 0 degrees to 110 degrees in 10 degrees steps. The tibial drill hole locations had only a minor effect on the changes in femorotibial distance. The most isometric point was located in the centre of the posterior intercondylar area. The femoral locations of the drill holes were the primary determinant of whether the distance increased, decreased or remained nearly constant. According to our results the most isometric femoral point is located at the posterosuperior margin of the anatomical PCL attachment. Using the tibial isometric point as a reference, the femoral points positioned anterior or posterior to the isometric point produced considerable changes in the femorotibial distance upon knee flexion. The anterior point led to an increase of about 7-8 mm at 110 degrees of flexion, the posterior point to a decrease of the same extent. Much smaller changes in femorotibial distance resulted from the points located superior or inferior to the femoral isometric point.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1502576 TI - [Reconstructive interventions of the posterior cruciate ligament--experimental studies of isometric aspects. Part II: Studies of the posterior cruciate ligament replacement model]. AB - Isometric positioning of the posterior cruciate ligament (PCL) graft is important for successful reconstruction of the PCL-deficient knee. This study documents the relationship between graft placement and changes in intra-articular graft length during passive range of motion of the knee. In eight cadaveric knees the PCL was identified and cut. The specimens were mounted in a stabilizing rig. PCL reconstruction was performed using a 9-mm-thick synthetic cord that was passed through tunnels 10 mm in diameter. Three different femoral graft placement sites were evaluated: (1) in four specimens the tunnel was located around the femoral isometric point, (2) in two specimens the tunnel was positioned over the guide wire 5 mm anterior to the femoral isometric point, (3) in two specimens the tunnel was positioned over the guide wire 5 mm posterior to the isometric femoral point. In all knees only one tibial tunnel was created around the isometric tibial point. The location of the isometric points was described in part I of the study. The proximal end of the cord was fixed to the lateral aspect of the femur. Distally the cord was attached to a measuring unit. The knees were flexed from 0 degree to 110 degrees, and the changes in the graft distance between the femoral attachment sites were measured in 10 degrees steps. Over the entire range of motion measured the femoral tunnels positioned around the isometric point produced femorotibial distance changes of within 2 mm. The anteriorly placed tunnels produced considerable increases in femorotibial distance with knee flexion, e.g. about 8 mm at 110 degrees of flexion.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1502577 TI - [Intra-articular calcaneus fracture. Classification in CT as a prerequisite for therapeutic decision and quantitative comparison]. AB - Whether conservative or operative management is selected for intra-articular fractures of the os calcis depends on subjective factors and on the surgeon's experience. There is no classification available that allows ranking of such fractures according to the extent of destruction and the degree of dislocation at the same time. CT scans of 44 calcaneal fractures have been used to elaborate a new classification system for calcaneal surfaces. According to the involvement of joint surfaces, especially of the posterior facet, the degree of dislocation and the number of fragments of the posterior facet, six classes are defined. Within each class of fracture, the formation of "steps" in the posterior facet, widening of the heel, loss of height and deviation of axes are quantified. The new classification provides an instrument for use in the evaluation of joint destruction and dislocation. It helps to provide an objective basis for decisions between functional treatment and open reduction with internal fixation and for prospective analysis of fracture treatment. PMID- 1502578 TI - The periphysis and its effect on the metaphysis: I. Definition and normal radiographic pattern. AB - The zone of Ranvier and the ring of LaCroix, together with the membranous bone bark they produce, are termed the periphysis in order to emphasize their normal effect (the metaphyseal collar) on the metaphysis of the infant and young child. In the first 7 years of life, the normal collar at the wrist is 1-3 mm wide. The step-off between the metaphyseal collar and the curvilinear metaphysis, at the margin of the periphysis, should not be mistaken for abuse fracture. The periphyseal bone bark may be radiologically visible at the edge of the physis at the distal ulna in 9% of infants and should not be mistaken for fracture or rickets. PMID- 1502579 TI - Plain radiographic predictors of survival in treated Ewing's sarcoma. IESS Committee. AB - We analyzed 16 radiographic features of primary Ewing's sarcoma in 342 patients from the IESS 7299 (Intergroup Ewing's Sarcoma Study) for prognostic significance. Of these, 3 features demonstrated a statistically significant relationship to survival: maximal tumor dimension, tumor location, and an appearance of honey-combing within the lesion. Those individuals with primary lesions centered in the pelvis, femur, or humerus had a worse survival rate than those with lesions centered elsewhere. Similarly, we observed an inverse relationship between the greatest dimension of the osseous portion of the lesion and survival. The radiographic finding of honeycombing also showed a statistical association with improved survival. However, this feature was observed infrequently, and its significance should be assessed further. Otherwise, no other feature that we analyzed showed any relationship to patient prognosis. PMID- 1502580 TI - Usefulness of an acoustic edge artifact in assessment of the Ilizarov corticotomy interval. AB - Thirty-three ultrasound examinations of the corticotomy interval of patients undergoing Ilizarov procedures were retrospectively evaluated for the presence or absence of an acoustic edge artifact. This artifact, consisting of a fine anechoic band, has been previously described in phantom models and is presumed to be due to phase cancellation effects. We demonstrated this artifact in 8 of 33 examinations. The artifact proved helpful in identifying the location of the corticotomy margin, even when this margin was obscured by the presence of developing periosteal new bone. Attention to technical factors is, however, important. We believe that this artifact may have a useful role in the routine monitoring of the Ilizarov patient. PMID- 1502581 TI - Ultrasonography after hip arthroplasty. AB - Ultrasonography was performed in 55 patients who had total Charnley hip arthroplasties. Effusions were identified in 19 patients and confirmed in all but 3 by arthrocentesis or at surgery. Aspirations were performed in 5 and demonstrated infection in 2. It is concluded that ultrasound is a valuable noninvasive method for assessing painful hip arthroplasty. It can demonstrate the presence of effusion, which should be aspirated to exclude infection. PMID- 1502582 TI - Proliferative periosteal processes of phalanges: a unitary hypothesis. AB - A unitary hypothesis is offered to explain the various proliferative processes occurring around the phalanges. In the past, these have been separately designated as proliferative periostitis, bizarre parosteal osteochondromatous proliferation, and turret exostosis. Because the appearances of these entities depend on temporal factors, breaching of the periosteum, and local anatomic features, we suggest a single term, proliferative periosteal processes of phalanges. PMID- 1502583 TI - More than just lip service. PMID- 1502584 TI - Patellofemoral characteristics in patients with increased femoral anteversion. AB - In this study, the association between increased femoral anteversion and the characteristics of the patellofemoral joint was investigated in adults. In 17 female control patients, the anteversion angle of the femoral neck measured 12 degrees +/- 8 degrees and 11 degrees +/- 9 degrees for the right and left side, respectively. The sulcus angle of the patellofemoral joint was 145 degrees +/- 10 degrees and 146 degrees +/- 11 degrees, the congruence angle 7.2 degrees +/- 14 degrees and 7.8 degrees +/- 15 degrees, and the lateral patellofemoral angle 5.9 degrees +/- 6 degrees and 5.7 degrees +/- 6 degrees, respectively. In 15 female patients who were evaluated for clinical symptoms of increased femoral anteversion, the anteversion angle of the femoral neck was 30 degrees +/- 7 degrees and 31 degrees +/- 8 degrees degrees for the right and left side, respectively. The sulcus angle was 143 degrees +/- 8 degrees and 147 degrees +/- 9 degrees, the congruence angle 7.3 degrees +/- 12 degrees and 7.1 degrees +/- 13 degrees, and the lateral patellofemoral angle 6.4 degrees +/- 8 degrees and 6.1 degrees +/- 7 degrees, respectively. There was no correlation between the degree of femoral anteversion and the indices of the patellofemoral relationships. Thus, this study indicates that there is no association between increased femoral anteversion and abnormal patellofemoral characteristics. PMID- 1502585 TI - Fracture-dislocation of the elbow with inferior radioulnar dislocation: a variant of the Essex-Lopresti injury. AB - We describe two patients with an Essex-Lopresti fracture dislocation in association with a dislocation of the elbow. This combination of injuries has not been previously reported. The Essex-Lopresti fracture is a rare injury, and the associated distal radioulnar dislocation is often missed. Meticulous radiographic evaluation of the wrist, including dynamic stress radiographs of the forearm, can lead to an earlier diagnosis and improved care of these patients. PMID- 1502586 TI - Case report 721: Intraarticular dislocation of a sesamoid in the first toe (type I). PMID- 1502587 TI - Case report 737: Cystic tuberculosis of femur. PMID- 1502588 TI - Case report 738: Osteoid osteoma of the patella. PMID- 1502589 TI - Case report 739: Tuberculous arthritis of knee. PMID- 1502590 TI - Case report 740: Giant cell tumor of the hamate bone. PMID- 1502591 TI - Case report 741: Chondromyxoid fibroma of T2. PMID- 1502592 TI - Case report 742: Intraosseous epidermoid cyst arising in the fifth metacarpal bone. PMID- 1502594 TI - Ecosystems: Microbes: Food. Society for Applied Bacteriology 60th Anniversary Symposium. Bristol, 16-18 July 1991. PMID- 1502593 TI - Case report 743: Urographic opacification following arthrography of the hip. PMID- 1502595 TI - The contribution of microbial ecology to management and monitoring of the safety, quality and acceptability (SQA) of foods. PMID- 1502596 TI - The relationship between the phenotypic properties of bacteria from chill-stored meat and spoilage processes. PMID- 1502597 TI - Ecosystems in vegetable foods. PMID- 1502598 TI - Membrane inlet mass spectrometry: probing the rumen ecosystem. PMID- 1502599 TI - Ecological concepts in food microbiology. PMID- 1502600 TI - Substrate capturing and growth in various ecosystems. PMID- 1502601 TI - Ecosystem approaches to food preservation. PMID- 1502602 TI - Modes of arrival and establishment of microfungi. PMID- 1502603 TI - Secondary metabolism and food intoxication--moulds. PMID- 1502604 TI - Modelling microbial ecosystems. PMID- 1502605 TI - Antibiotics and the selection of food-borne pathogens. PMID- 1502606 TI - Estrogen therapy for geriatric osteoporosis: just one ball in a complex juggling act. AB - The use of estrogens is the single therapy that has been found consistently to prevent bone loss and fractures in postmenopausal women. Traditional osteoporotic risk factors should be used to select women for bone densitometry. The numeric result provided by densitometry, combined with age-based comparisons, is extremely useful in convincing reluctant women to be treated. The few studies that have been done in geriatric women show that estrogen therapy continues to be effective in reducing bone loss, but the absolute benefit is less than in perimenopausal women. The effects of estrogen therapy extend beyond osteoporosis. A consensus of epidemiologic reports has shown that women who comply with postmenopausal estrogen therapy have a 30% to 50% reduction in the risk of coronary artery disease. Given the frequency of these two conditions, widespread use of estrogen as a national health care policy would be appropriate if it were not for the evidence that estrogens may increase the risk of breast cancer and endometrial cancer. Given these lingering cancer fears, recent calls for a randomized national women's health study of postmenopausal estrogen therapy should be heeded. PMID- 1502607 TI - Calcitonin therapy in osteoporotic syndromes. PMID- 1502608 TI - Role of calcium in preserving the skeletal health of aging women. AB - During the years from adolescence through senescence, the skeleton passes through identifiable phases: consolidation, maturity, menopause, and senescence. Skeletal dynamics and calcium requirements are different during each phase. A adult woman can avoid the skeletal deterioration caused by calcium deficiency if she maintains a minimum daily calcium intake of 800 mg. Increased calcium intake will not increase skeletal mass in mature, premenopausal women and will not prevent bone loss in postmenopausal women. Because intestinal absorption decreases with age, daily calcium intake of 1000 to 1200 mg is recommended for the elderly. Women can increase their dietary calcium intake in various ways, including increasing intake of dairy products, eating calcium-rich nondairy foods, purchasing foods fortified with calcium, and, if all other methods prove inadequate, using calcium supplements. Physicians must prescribe calcium only after learning what is needed for a particular woman's skeletal health by determining that woman's stage of skeletal development and approximate calcium intake; if intake is insufficient, it should be adjusted to the level appropriate at that stage. PMID- 1502609 TI - Bisphosphonate therapy for postmenopausal osteoporosis. AB - Bisphosphonates are agents that are potentially useful for treatment of osteoporosis. They are antiresorptive agents, increasing bone mass by decreasing the frequency of osteoclast activation or the depth of osteoclast resorption, or both. Intermittent cyclical therapy with etidronate has been shown to be effective for postmenopausal osteoporosis in two controlled studies. Several second- and third- generation bisphosphonates are undergoing active clinical trials. PMID- 1502610 TI - Fluorides and osteoporosis. AB - Sodium fluoride has clearly been shown to have pronounced effects on the skeleton, probably more than any other currently available therapeutic agent. Unfortunately, these effects appear to be both beneficial and potentially toxic at the same time. A more clear understanding is needed of the basic mechanisms whereby these effects (both beneficial and detrimental) are exerted. When such data are forthcoming, it may be possible to modify the therapeutic use of fluoride in osteoporosis and other brittle bone diseases such that the beneficial effects outweigh the toxic effects much more completely than is currently the case. Until such time, and despite thirty years of meaningful clinical investigation, we must conclude that sodium fluoride has no role in clinical medicine outside the confines of properly conducted clinical research studies. PMID- 1502611 TI - Osteoporosis: The problem. PMID- 1502612 TI - Osteoporosis: contemporary issues on diagnosis and drug management. Proceedings of the sectional meeting of the Southern Association for Geriatric Medicine. Atlanta, Georgia, November 15, 1991. PMID- 1502614 TI - Glucocorticoid-induced osteoporosis. AB - The incidence of osteoporosis in patients receiving long-term glucocorticoid therapy is 30% to 50%. Trabecular bone is lost more rapidly than cortical. The cause of glucocorticoid-induced bone loss is multifactorial. Gastrointestinal absorption of calcium falls and urinary excretion rises, production of gonadal hormones decreases, and bone formation is inhibited in the presence of glucocorticoids. Bone loss can be minimized by using the lowest effective dose of a glucocorticoid with a short half-life, maintaining good nutritional status and physical activity, limiting sodium intake and giving a thiazide diuretic, maintaining serum 25-OHD at the upper limits of the normal range, giving estrogen replacement therapy to postmenopausal and amenorrheic women, and giving testosterone to men with low serum testosterone levels. The use of calcitonin or bisphosphonates should be considered. PMID- 1502613 TI - Vitamin D metabolism and therapy in elderly subjects. AB - Serum 25-hydroxyvitamin D declines in elderly subjects. This decrease reflects, in part, a lower vitamin D intake. But changes in serum 25-hydroxyvitamin D are more marked in the northern latitudes of the world because less vitamin D synthesis occurs n the skin as a result of a reduced amount of ultraviolet light. Consequently, vitamin D deficiency leading to osteomalacia is more common in thr northern latitudes, particularly among the elderly. The Recommended Daily Allowance of 200 IU of vitamin D in the elderly may be insufficient, since higher doses of 800 IU/day have been shown to reduce the incidence of osteoporotic fractures. The use of more potent analogues of vitamin D, such as calcitriol (Rocaltrol), should be reserved only for those patients who have established vertebral osteoporosis and who generally have more pronounced malabsorption of calcium. PMID- 1502615 TI - Perspectives in the use of newer bisphosphonates in the management of established osteoporosis. PMID- 1502616 TI - The right to die: legal and ethical considerations. PMID- 1502617 TI - Mercy killing. PMID- 1502619 TI - Quackery: the modern highwayman. PMID- 1502618 TI - Diagnosis of osteoporosis. PMID- 1502620 TI - Increased incidence of syphilis in Tennessee during the 1980s: challenges for a new decade. AB - Although recent increases in the incidence of syphilis are well known to public health officials, the general medical community is less well informed regarding the dramatic rise in cases. We present trend data from Nashville and Tennessee over the past decade. These statistics emphasize specific factors, such as drug abuse, that contribute to new difficulties in controlling this sexually transmitted disease. PMID- 1502621 TI - Comparability of alcohol and drug use in injured drivers. AB - During a recent 5-month period, 201 injured drivers were admitted to a level 1 trauma center. Blood alcohol concentrations (BACs) and drug screens were obtained in 187 and 164 subjects, respectively. BACs were positive in 37% and other drugs were confirmed in 40%, suggesting that alcohol and drug use among injured drivers is comparable. More than half of the drivers using alcohol also had drugs detected on the screening examination. Other investigators have previously established driving impairments associated with some of these drugs. These results indicate that the drug problem on our highways may be greater than previously recognized. PMID- 1502622 TI - Acute phenobarbital intoxication. AB - Phenobarbital is a long-acting barbiturate often prescribed for seizure disorders. It has a high abuse potential and was commonly used in suicide attempts in the past. Although benzodiazepines are now more frequently used in suicide attempts, barbiturate intoxications are still occasionally seen and constitute a medical emergency. The management of phenobarbital overdose includes cardiac and respiratory support, cathartics, activated charcoal, and alkaline diuresis. In severely compromised patients, hemodialysis and hemoperfusion can be used to enhance drug clearance. PMID- 1502623 TI - Reconstruction of calvarial defects. AB - We subdivide the calvarium into three zones, each with its special reconstructive requirements. Based on our experience with calvarial defects in 13 patients, we favor use of autogenous material, especially in the face of previous infection or a scarred recipient bed. Alloplasts give excellent forehead contour but alloplastic reconstruction should be delayed for 1 year after injury. Vascularized bone grafts maintain contour well. They are best suited to large periorbital defects. At other locations we favor split calvarial free bone grafts. Occasionally, the defect may be so large as to warrant grafts from multiple donor sites. Use of vascularized muscle helps eradicate infection, provides a vascularized bed for free bone grafts, and fills dead space. The frontal sinus is managed either by cranialization (if the posterior wall is involved) or by mucosal stripping with obliteration of the nasofrontal duct. Additional technical considerations include rigid bone fixation, surgical exposure through a bicoronal incision, and meticulous handling of bone grafts. PMID- 1502624 TI - Severe essential tremor compared with Parkinson's disease in male veterans: diagnostic characteristics, treatment, and psychosocial complications. AB - Essential tremor (ET), more common than Parkinson's disease (PD), has commonly been considered "benign." This investigation compared diagnostic characteristics, patient satisfaction with treatment, and psychosocial complications between a group of male patients treated for essential tremor and a group of male parkinsonian patients. Those who had ET tended to be more commonly misdiagnosed than those with PD. Fewer ET patients were satisfied with response to treatment than PD patients. Both groups equally expressed embarrassment about their condition, and both perceived similar difficulties with common activities of daily living and social situations. There were no significant differences between ET and PD patients for history of ethanol use or pharmacotherapy for anxiety or depression. PMID- 1502625 TI - Hickman catheter malposition in central venous tributaries: an avoidable error? AB - We report three cases of erroneous positioning of Hickman catheters into central venous tributaries. The malposition was not diagnosed intraoperatively because of proximity of such veins to the superior vena cava. Suspicion of misplacement raised by early postoperative catheter malfunction should allow for correction by percutaneous vascular catheters. PMID- 1502626 TI - Clinical management of postmenopausal osteoporosis. AB - Today, 24 million Americans are at risk for osteoporosis. Of the 2 million fractures that occur each year in the United States, approximately 1.3 million are directly due to osteoporosis. Osteoporosis, a preventable and treatable condition, takes on great importance because of the enormous impact these fractures can have on mortality, health care costs, patient productivity, independence, and self-esteem. Advances in diagnostic techniques and improved understanding of risk factors allow clinicians greater acumen in the classification and diagnosis of osteoporosis. Today, FDA-approved therapy for the treatment of postmenopausal osteoporosis includes calcium and vitamin D supplementation, estrogen and progesterone, and calcitonin-salmon. This article presents a review of the current understanding of each of these as well as experimental forms of therapy. PMID- 1502627 TI - Physician-executives past, present, and future. AB - The dramatic changes in the United States' health care system during the last decade have sparked increasing interest in physician-executives. These executives, skilled in both clinical medicine and health care management, can be found in hospitals, managed care organizations, group practices, and government institutions. This paper outlines the physician-executive's roles and the development process. The remarkable growth in the number of physician-executives is expected to continue as they demonstrate their abilities to help health care providers expand ambulatory services, facilitate provider-physician relationships and physician recruitment, and lend expertise in quality improvement and risk management issues. PMID- 1502628 TI - Raccoon heartworm causing a facial mass. AB - A Dirofilaria tenuis subcutaneous nodule was found in the supraorbital area of a 77-year-old woman living in Miami Beach. Removal of this nodule revealed the worm and confirmed the diagnosis. Infection with Dirofilaria tenuis is most common in southern Florida because of the high incidence of these worms in their natural hosts--raccoons and opossums. PMID- 1502629 TI - Tension pneumothorax as a presentation of traumatic diaphragmatic hernia. AB - Spontaneous pneumothorax and tension pneumothorax are being increasingly recognized as complications of traumatic diaphragmatic hernia, particularly when presentation is delayed. This underscores the importance of suspecting the diagnosis of diaphragmatic hernia in patients with a recent or remote history of blunt or penetrating trauma to the chest or abdomen and an unusual or an atypical thoracic process. Once the diagnosis is suspected, confirmation with contrast studies, CT, or MRI should be obtained and surgical repair undertaken without delay. PMID- 1502630 TI - Abdominal pain resulting from cerebrospinal fluid pseudocyst and cholelithiasis. AB - Patients treated with ventriculoperitoneal (VP) shunt procedures for hydrocephalus may have abdominal pain related to complications stemming from the shunt tubing itself or to other intra-abdominal disease. In patients with VP shunts, usually children, lack of absorption of cerebrospinal fluid (CSF) may produce a painful abdominal CSF pseudocyst. We have reported the rare occurrence of a CSF pseudocyst in an adult. The patient was also found to have cholelithiasis. PMID- 1502631 TI - Severe hypertension associated with an intrarenal aneurysm. AB - A 26-year-old woman with regularly documented normal blood pressure had sudden onset of severe hypertension. Investigation revealed an intrarenal artery aneurysm involving the upper pole of the left kidney, as well as elevated levels of both renin and aldosterone. With ACE inhibitor therapy, blood pressure promptly returned to normal, and subsequent surgical removal of the upper pole of the involved kidney has resulted in normal blood pressure for 9 months of follow up. Although uncommon, intrarenal aneurysms may lead to severe renal vascular hypertension that is relieved by surgery. This definitive procedure may not take place if one is not aware of the excellent response to ACE inhibitors in this situation. PMID- 1502632 TI - Complementary role of radionuclide and CT scans in the diagnosis and management of emphysematous pyelonephritis. PMID- 1502633 TI - Multiple epiphyseal dysplasia. PMID- 1502634 TI - Syphilis screening in a suburban community. PMID- 1502635 TI - Morphology of the dens. A quantitative study. AB - Morphometric studies of the dens of the second cervical vertebra were performed on a sample of one hundred twenty bones from the Hamann-Todd Collection. Data were collected on the longitudinal and transverse dimensions of the dens, as well as the size of the dens relative to the centrum of C2. Relationships of dens dimensions to body size and sexual dimorphism were evaluated. In both longitudinal and transverse mean dimensions, the dens in males was slightly, but significantly larger (5-10%) than in females. The relative distributions of dens dimensions were consistently skewed toward the higher values in males and the lower values in females. Body height or weight were not significantly correlated with dens dimensions, and were therefore poor predictors of the size of the dens. Implications for screw fixation of fractures of the dens are discussed. PMID- 1502636 TI - The prevalence of cervical zygapophyseal joint pain. A first approximation. AB - A null hypothesis was tested to the effect that cervical zygapophyseal joint pain was uncommon. The prospectively recorded responses were reviewed of 318 consecutive patients with intractable neck pain who underwent provocation discography and cervical zygapophyseal joint blocks. Symptomatic zygapophyseal joints were encountered in 25% of the sample with a possibility that a further 38% suffered zygapophyseal pain but were not appropriately investigated. The null hypothesis was rejected. Cervical zygapophyseal joint pain is not rare, and is worthy of further consideration not just in research but in clinical practice. PMID- 1502637 TI - Abnormal instantaneous axes of rotation in patients with neck pain. AB - Instantaneous axes of rotation for cervical motion segments C2-3 to C6-7 were determined in 109 patients with uncomplicated neck pain. Their location in each patient was compared to normal ranges determined in a previous study of 46 asymptomatic individuals. Unequivocally abnormal instantaneous axes of rotation were found in 46% of patients, and marginally abnormal instantaneous axes of rotation were found in a further 26% of patients. Abnormal instantaneous axes of rotation significantly correlated with the presence of neck pain, but the location of an abnormal axis did not correlate with the segmental source of pain as determined by provocation discography or zygapophyseal joint blocks. PMID- 1502638 TI - Spinal mobility and posture in adolescent idiopathic scoliosis at three stages of curve magnitude. AB - Spinal posture and mobility were studied in 71 girls with progressive adolescent idiopathic thoracic scoliosis. Measurements were carried out by inclinometers and a compass in three planes; sagittal, frontal, and horizontal. The patients were divided into three groups according to the curve magnitude. Group 1 had curves smaller than 25 degrees, group 2 had curves between 25 and 35 degrees, and group 3 had curves greater than 35 degrees. The positional inclines of sacrum, upper lumbar and upper thoracic areas became more vertical as the curve size increased resulting in smaller lumbar lordosis and thoracic kyphosis. In the thoracic spine flexion and bending to the right was smaller in group 3 than in the other groups. Rotations in both clockwise and counterclockwise directions decreased as the curve size increased. In the lumbar spine only bending to the left decreased significantly with the curve size increase. All thoracic and lumbar movements except lumbar rotations had a general tendency to stiffening as the curve size increased. Of the mobility measurements thoracic rotation most clearly decreased with increased curves, which together with straightening of the spine can be important features in the pathomechanism of a progressive idiopathic thoracic curve. PMID- 1502639 TI - Diurnal changes in the profile shape and range of motion of the back. AB - The diurnal height change reported to occur in young adults was investigated to characterize changes in the lumbar range of motion, spinal profile, and range of motion of the back. Twelve subjects aged 18-22 years were measured using stereophotography and standard clinical examinations in the evening and after a minimum of 8 hours of complete bed rest. The average increase in height was 20 mm. Forty percent of the height increase took place in the lumbar spine without change in the depth of the lordosis, and forty percent took place in the thoracic curve with a decrease in the kyphosis. The remaining 20% of the height increase was not located, but no measurements were taken of the cervical spine. Range of motion studies revealed that lumbar flexion, as measured using the lumbar flexion increment, was decreased in the morning, and straight leg raise was decreased when measured clinically but not when measured photographically. Extension, rotation, and femoral stretch test were not affected. The authors conclude that stereophotogrammetry offers an accurate, noninvasive way to study spinal profiles. Further work is needed to assess and quantify the relative motion of the skin and the underlying structures. PMID- 1502640 TI - Morphologic and histochemical characteristics of skeletal muscle after long-term intramuscular electrical stimulation. AB - The purpose of this investigation was to examine the morphologic and histochemical characteristics of paraspinal muscles in patients with scoliosis after long-term electrical stimulation. Thirty-six children with idiopathic scoliosis, who had been treated with implantable muscle stimulators, had paraspinal muscle biopsies at the time of implantable muscle stimulator removal. Group A patients whose curve did not progress, had 2.9 years of stimulation stopped at skeletal maturity, with a further 1.5 years of nonstimulation before implant removal and biopsy. In group B patients, who had an average of 2.3 years of stimulation, the curve progressed and stimulation was continued until fusion and biopsy. Neither group showed any increase in the frequency of pathologic changes of paraspinal muscles contrasted with values reported in the literature for scoliotic muscle. In group A patients there was an increased proportion of type 1 fibers on the convex side of the curve compared to the concavity. Despite this finding the curves did not require fusion, suggesting that the increased percentage of type 1 fibers was not the cause of the scoliosis. In group B patients there was an even higher type 1 concentration on the convex side contrasted to the convex side of group A patients. PMID- 1502641 TI - A comparative study of computed tomographic and plain radiographic methods to measure vertebral rotation in adolescent idiopathic scoliosis. AB - A comparative analysis of two methods of measuring vertebral rotation in adolescent idiopathic scoliosis is reported in this article. Nash and Moe's pedicle shift method (using plain anteroposterior radiographs) is compared with a new method using computed tomographic scans. The computed tomographic scans of the whole length of the major curve and the scout films obtained from seventeen girls aged 12.5-14 years were measured for rotation of each vertebra of the curve (total number of vertebrae measured by two methods = 173). This study has three interesting new findings: 1) Those vertebrae with Nash & Moe grade 0 had up to 11 degrees of vertebral rotation when measured using the computed tomographic method. Therefore, Nash & Moe's grade '0' is not a neutrally rotated vertebra; 2) For Nash & Moe grade 1 and 2, the computed tomographic method revealed statistically significantly greater rotation for lumbar vertebrae than thoracic vertebrae. There was a similar pattern for Nash & Moe grade 0 but these differences were not statistically significant; and 3) Simple formulae are reported to convert Nash & Moe's grades into angle of vertebral rotation as obtained by CT method separately for thoracic and lumbar vertebrae. PMID- 1502642 TI - Changes in vertebral rotation after Harrington and Luque instrumentation for idiopathic scoliosis. AB - This study was carried out to analyze the three-dimensional and in particular the rotational correction obtained after spine instrumentation for idiopathic scoliosis. Preoperative and postoperative radiographs and computed tomographic scans with single axial cuts through each vertebral level were obtained for 14 patients: 4 Harrington, 7 Luque, and 3 Harrington-Luque. Rotation of vertebrae relative to the spinal axis and rotation between vertebrae (segmental rotation) were measured from computed tomographic scans of instrumented and uninstrumented segments. The derotation and changes occurring after surgery were calculated. Before operation, rotation was maximal at the apex, and close to 0 at the end vertebra; segmental rotation was greatest at the end of the curve, and minimal at the apex. After Harrington instrumentation the apical vertebrae showed a median derotation of 16%, after Luque instrumentation it was 12% and after Harrington Luque instrumentation it was 13%. Segmental derotation did not uniformly occur. Major derotation was obtained at the end vertebrae and 39% of the total derotation occurred outside of the instrumented levels of the spine. PMID- 1502643 TI - Mechanisms of curve progression following sublaminar (Luque) spinal instrumentation. AB - Fifty-two patients with Luque instrumentation were reviewed for spinal deformities. Forty-two patients were reviewed during 1 year (longest 7.2 years) at follow-up. Two patients were included who lost correction within 1 year (both 8 months). Follow up averaged 2.9 years. Curve causes primarily were neuromuscular but included one was caused by idiopathic scoliosis, four by Scheuermann's disease, and 1 by post-laminectomy kyphosis. The Cobb angle progressed in 45% of patients postoperatively. Factors contributing to progression included progressive vertebral rotation or the crankshaft phenomenon (11), wire pull out (7), progressive pelvic obliquity (4), rod bending (3), pseudarthrosis (2), and rod migration (2). Factors correlating with progression were kyphosis, postoperative curve greater than 35 degrees, preoperative curve greater than 60 degrees, and not fusing to the pelvis in nonambulators. Crankshaft was common in patients Risser II or less but did not occur in more mature patients. PMID- 1502644 TI - Iliac crest versus spinous process grafts in posttraumatic spinal fusions. AB - Results of posttraumatic spine fusions in 34 patients who had autogenous iliac crest grafts were compared with those of 70 patients who had autogenous spinous process grafts. The two groups of patients were otherwise homogenous, and fusion occurred in 32 (94%) of the iliac crest graft patients and 70 (100%) spinous process graft patients. However, average operative time (225 vs. 200 minutes) and operative blood loss (1371 vs. 1136 cc) were significantly higher in iliac crest graft patients (P less than 0.05), and five iliac crest graft patients had significant donor site complications. Use of spinous process grafts eliminated donor site problems, reduced operative time and blood loss, and produced a rate of arthrodesis equal to that of iliac crest grafts. PMID- 1502645 TI - Quantitative histologic study of the influence of anterior spinal instrumentation and biodegradable polymer on lumbar interbody fusion after corpectomy. A canine model. AB - Histomorphometric and microradiographic studies were performed to investigate whether there are different rates of bone remodeling based on the intrinsic stability with anterior spinal instrumentation and to evaluate if biodegradable polymer could be used clinically as the material of choice for anterior spinal instrumentation. Twenty-one coon hounds underwent anterior and posterior spinal destabilizing procedures to produce a reproducible amount of spinal instability: corpectomy of L5, discectomies and partial facetectomies of L4-5 and L5-6, resections of L5 lamina, spinous process, supra- and interspinous ligament, and ligamentum flavum. Group 1 (N = 7) underwent anterior autogenous ulna strut graft alone at L4-6; group 2 (N = 7) underwent anterior biodegradable polymer strut alone at the same level; group 3 (N = 7) underwent same bone graft as in group 1, augmented by anterior Kaneda device. Six months after surgery quantitative histologic study showed that device-related osteopenia occurred in spines treated with Kaneda device. Within the L5 vertebral body the volumetric density of bone (mm3/cm3) was less for the group with Kaneda device (group 3) compared with that without instrumentation (group 1, P less than 0.05). In the spine treated with biodegradable polymer, no adverse host tissue responses were observed histologically. In addition, osteoconductive abilities of the polymer were suggested microscopically. Its mechanical property, however, was not rigid enough to stabilize the corpectomized spine. PMID- 1502646 TI - The biomechanics of lumbar facetectomy under compression-flexion. AB - Alterations of posterior spinal elements including the facet joints are commonly associated with a variety of lumbar operative procedures. Under continuous physiologic compression-flexion load application L2-L3 and L4-L5 functional units were tested as intact preparations and then sequentially altered with unilateral facetectomy, bilateral facetectomy, posterior ligament transection, and partial discectomy. Using a method of continuous motion analysis, the movement of the individual spinal components (disc, facet joint, interspinous process distance) were statistically compared between the various surgical alterations. Higher physiologic loads produced significant increases in overall deflection from BF to BFL alterations indicating a preference to preserve the posterior ligaments for this surgical approach. Although insignificant changes in the force-deflection response from one surgical alteration to the next sequential alteration were noted, statistically significant increases in localized facet joint motion may suggest the potential for acceleration of segmental degenerative changes. PMID- 1502647 TI - Induced narrowing and back adaptation of lumbar intervertebral discs in biomechanically stressed rats. AB - The purpose of this work was to develop an animal model of chronic low-back dysfunction induced by biomechanical stress. The intervertebral disc size was measured by radiography and histology in control rats, in rats intermittently forced to ambulate on a flat surface or in cylinders. Forced ambulation in cylinders caused rats to assume a relative extensive posture in the low back. Lumbar discs in biomechanically stressed rats initially narrowed, and after months of continued intermittent stress, regained near-normal size in vivo, shown by radiography. By using histologic methods, discs from rats that ambulated in any posture were shown to be larger than discs from rats not forced to ambulate. The results were consistent with the hypothesis that in vivo discs in biomechanically stressed rats initially narrow due to compressive loading and then widen back toward normal size because of an altered matrix which has increased imbibing properties. According to this hypothesis altered matrix synthesis in the nucleus pulposus was an adaptation induced by the cyclic compressive loading associated with ambulation. PMID- 1502648 TI - Computer tomographically guided discography as a determinant of normal disc level before fusion. AB - Computer tomographically guided discography was used as a reproducible and reliable method of determining the internal architecture and integrity of intervertebral discs before spinal fusion operation. One hundred disc levels were studied in 60 prospective patients with 54 (54%) of levels proving abnormal. Twenty-nine levels (29% of total levels) demonstrated complete anular tears, and 25 (25% of total) showed incomplete radial tears of the anulus, often multiple, indicative of degenerative change. In each of these cases, one level higher had to be studied and was subsequently found to be normal and would, therefore, support a fusion. PMID- 1502649 TI - Anterior lumbar interbody fusion for internal disc disruption. AB - Anterior lumbar interbody fusion was performed as the primary surgical procedure for 36 patients with internal disc derangement. Patients were selected on the basis of clinical complaints, discography, and magnetic resonance imaging results. Twenty-eight patients underwent a one-level fusion and eight patients had a two-level fusion for a total of 44 levels. Autogenous graft was used in all cases. Clinical results were categorized as success or failure based on return to work or activities of daily living, drug usage patterns, and complaints of pain. Thirty-one patients (86.1%) had a successful clinical result and five patients (13.9%) had an unsuccessful clinical result. Based on flexion-extension radiographs fusion was achieved in 32 patients (88.9%). Forty of the forty-four levels (90.9%) fused. Complications include one each of: pulmonary embolus, retrograde ejaculation, wound hematoma at the donor site, and perioperative graft extrusion. PMID- 1502650 TI - Clinical efficacy of spinal instrumentation in lumbar degenerative disc disease. AB - In review of 871 lumbar fusion procedures performed during the last 8 years, the theoretical advantages of lumbar spinal instrumentation are not borne out in simple discogenic disease. Four groups of 30-35 patients without previous surgery who underwent fusion by different techniques were matched for age, sex, length of follow-up, surgeons, number of levels fused, duration of preoperative symptoms, diagnosis, and type of third party payer. At least for the diagnoses of herniated disc with segmental instability and the instrumentation systems used in this study, results were superior with no internal fixation. This is in keeping with the higher complication rates and frequent need for implant removal reported by many authors. PMID- 1502651 TI - Chemonucleolysis. Predictive factors. AB - The aim of this study was to identify factors in the patient's history and parameters of the neurologic, roentgenographic, and electromyographic examinations as well as cerebrospinal fluid analysis before chemonucleolysis that might be used to predict the results of this treatment after 1 year. On the basis of a combination of three factors, that is, the presence or absence of a narrowed intervertebral space on the lumbosacral survey film, the localization of the disc herniation (medial, mediolateral or lateral) on the computerized tomographic scan and the number of cells in the cerebrospinal fluid, a satisfactory result could be predicted for 92% of the patients. PMID- 1502652 TI - Aneurysmal bone cyst of a thoracic vertebra. Treatment by selective arterial embolization and excision. PMID- 1502653 TI - Idiopathic scoliosis with unusual stress fracture of the pedicle within solid fusion mass. A case report. PMID- 1502654 TI - Scoliosis caused by rib fusion after thoracotomy for esophageal atresia. Report of a case and review of the literature. PMID- 1502655 TI - A congenital spinal arachnoid diverticulum expanded into the retropleural cavity. A case report and short literature review. PMID- 1502656 TI - [First meeting of the Mexico-United States Committee on Environmental and Occupational Health]. PMID- 1502657 TI - [Direct costs of the treatment of AIDS in Mexico]. AB - This report presents the results of a study of direct treatment costs of AIDS in Mexico, carried out in five public hospitals, four social security hospitals and one private hospital. The study included: a retrospective phase, a prospective phase and a longitudinal followup. The study found that the average AIDS patient has a total of two hospital admissions per year, with an average stay of 20 days per admission, and an annual cost of almost $4,043 US. The hospital admission costs per patient ranged between $1,430 US and $7,350 US with an average cost of $2,565 US. The outpatient's treatment costs per year were of $300 US. The patient's expenses at their homes were $1,100 US. We conclude that treatment costs for AIDS patients, excluding use of AZT, are higher than the treatment costs of comparable diseases. The greatest cost is that for inpatient care; thus, we recommend improving outpatient care services in order to provide more comprehensive care to patients and their families. PMID- 1502658 TI - [Liver cirrhosis mortality in Mexico. I. Relevant epidemiological characteristics]. AB - Previous studies have emphasized the impact of alcoholism on public health, especially on the incidence of liver cirrhosis, which ranks among one of the main causes of death in Mexico. Accordingly, the epidemiologic features of liver cirrhosis mortality (LCM) are examined, highlighting its historical trends, its geographical distribution and other risk factors like age and sex. The data show a consistently high LCM rate over time, male rates moving slightly up and female rates down. Proportional mortality has been increasing. The significant risk increment with age has determined LCM to be the leading cause of death for both sexes in the 30-64 years age group. A particularly interesting finding relates to the continuous excess of LCM seen in Mexico City and four surrounding states; on the contrary, in the northern states, LCM is considerably low. This difference is valid for women too. Comparing all states, a gradient of LCM rates from high to low mortality areas is observed. The social and health implications of LCM regional distribution demand the conduction of epidemiological studies to identify possible explanatory variables related to the pattern of alcohol consumption or other risk factors. Nonetheless, these data alone justify the implementation of an effective action plan in the high-risk areas to deal with this health problem, inherently associated with individual and social behaviors. PMID- 1502659 TI - [Liver cirrhosis mortality in Mexico. II. Excess mortality and pulque consumption]. AB - Over the years high cirrhosis mortality rates have been reported in Mexico City and in the surrounding states (Hidalgo, Tlaxcala, Puebla and the State of Mexico); on the contrary, well defined areas, such as the northern states, have shown a considerably lower mortality rate. This situation may indicate that some factors such as the pattern of alcoholic intake and other environmental characteristics could explain this striking difference. To determine the role of alcohol, the availability and consumption of alcohol at regional and state level were compared with cirrhosis mortality rates. A high and statistically significant correlation was found with pulque availability and consumption (r = 72-92%, p less than 0.01) in all periods of time under examination. On the contrary, a statistically significant negative association was observed with beer consumption and a positive, but not significant correlation, with distilled alcoholic beverages. Infectious hepatitis incidence, prevalence of exclusive use of native languages (as an indirect index of ethnic background) and nutritional deficiencies were also studied as possible risk factors. Nutritional deficiencies and the prevalence of exclusive use of nahuatl and otomi languages were positively correlated. These results can be useful to conduct further epidemiological studies still needed to determine the etiologic role of pulque consumption as well as of the other risk factors. Nonetheless, the current data stress the need to implement public health programs to reduce alcohol consumption, especially pulque, and to minimize the impact of these risk factors in high mortality areas. PMID- 1502660 TI - [Contraceptive practices among adolescents and youths of the metropolitan area of Mexico City]. AB - The purpose of this article is to provide a brief description of the information that the adolescent and youth population of Mexico City has concerning the knowledge and use of contraceptive methods, as well as the reasons why they do not adopt some contraceptive method during their sexual relations. The data obtained from the Survey on Adolescent and Youth Reproductive Behavior in the Metropolitan Area of Mexico City serves as a basis for pointing out several behavior patterns of the male and female population from 10 to 25 years of age. Of those interviewed, 32.7 per cent had had at least one sexual contact; the average age at which sexual relations had begun was 16 years for males and 17 for females. A total of 33.8 per cent of those who had had sexual contact stated that they had used some form of contraception, the principal methods used during first sexual intercourse being rhythm (36.9%); withdrawal (23.6%), and condoms (12.3%). The reasons for not using any contraceptive method were as follows: lack of knowledge regarding the methods, how to use them or where to obtain them (39.4%), and unplanned sexual intercourse (28.9%). During the last sexual contact they had, 70.5 per cent had used a contraceptive. The methods most frequently used were hormonal contraceptives and IUD (40.9%); rhythm (23.8%), and withdrawal and condoms. The reasons why no contraceptive was used in the last sexual contact were: neither partner thought that pregnancy would occur (27.1%) and the sexual contact was unplanned. PMID- 1502661 TI - [Supply of medical equipment in Mexico]. AB - This article covers the report on Supply of Medical Equipment in Mexico, presented during the Second National Congress of Public Health. The results are part of an investigation that dealt with the general conditions that currently prevail in the production and distribution of medical equipment. The information was obtained by means of a survey applied to 208 companies that comprised the sample study. The facts indicate that of the companies that correspond to this industrial sector in Mexico, 3.8 per cent are manufacturers, 69.7 per cent distributors, 19.2 per cent manufacturer-distributors, and the remaining 7.2 per cent correspond to corrective and preventive maintenance. Also, these companies pose serious problems of external dependence with regard to production costs and the commercialization of products. Furthermore, it became evident that there is a substantial need for financial support to optimally satisfy the demands of various institutions in the country's health sector. PMID- 1502662 TI - [Evaluation of heart rate and blood pressure in residents of Milpa Alta, D.F]. AB - Both the altitude of Mexico City (D.F.) and the increase in atmospheric pollutants make it important to establish parameters of comparison for cardiovascular variables, such as heart rate (HR) and blood pressure (BP). The epidemiological transition occurring in Mexico is increasing the need for human and physical resources at the first level of health care in order to perform early diagnoses of cardiovascular disorders among the population. Heart rate, systolic and diastolic blood pressures (SBP, DBP) were recorded under diverse conditions (seated, standing, performing 30 sit-ups, and then standing and seated after the sit-ups) in 235 inhabitants of Milpa Alta (a suburb of Mexico City). The procedures and equipment used were designed and produced at the Center for Development and Technological Applications, Ministry of Health. The following results were found: HR decreases with age and body surface. Likewise, the HR increase due to exercise is lower with increasing age and larger body surface and its return to resting levels is slower. SBP and DBP magnitude is directly related to body surface. In women an increase of body weight was found to be significantly related to a higher SBP. The orthostatic reflex (OR) decreases with age and body surface. The descending slope is higher in women than in men. We propose that the study of OR could provide better information for predicting cardiovascular changes. The described procedures can be performed with the physical and human resources available at the Health Centers. The extension of this type of applied research to first level health care centers would allow the country to respond efficiently to the epidemiological transition. PMID- 1502663 TI - [Determinants of the development of professional patterns in medical students]. AB - This paper reports the preliminary results of a research work aimed at establishing some determinants of the development of professional patterns in medical students. We present the results of a cohort of medical students in which we explored the type and frequency of general and specialized reading, family and friendship ties within the profession and some educational elements. These three aspects are associated with some aspects of professional patterns. The first statistical estimations show a strong influence of family ties. The presence of a family member or a close friend related with the medical profession strongly influenced the development of traditional beliefs about the medical profession, its practice, and the features of contents and areas of knowledge. Reading of newspapers and specialized journals by the students was used to explore cultural socialization, and this was found not to influence definitely the patterns of the profession. As for the influence of some educational elements, their participation is not clear, and further studies are needed to disclose it. Finally, we point out some questions emerging from this first approach to this information, and future research lines to be addressed. PMID- 1502664 TI - [Between the public and the private. New incentives in health care]. AB - This paper discusses some of the proposals regarding the improvement of the efficiency in the delivery of health care services. Several countries have implemented different strategies based on the experience of the Health Maintenance Organizations, which have used the market to stimulate competition between providers and insurance companies. One of the proposals includes the creation of agencies that would compete in quality and in price. Another one implies the creation of a National Health Service capable of hiring public or private services from local agencies. The ideal strategy would enable a consumer to choose between insurance companies and public and private providers, and would hopefully create cost conditions reasonably correlated with the efficiency and quality of the rendered services. PMID- 1502665 TI - [Carlos J. Finlay]. PMID- 1502666 TI - [Precocious and late puberties]. PMID- 1502667 TI - [Menometrorrhagia in puberty]. PMID- 1502668 TI - [Anorexia, bulimia and pregnancy in adolescents]. PMID- 1502669 TI - [A pause to be reborn]. PMID- 1502671 TI - [Artificial nursing]. PMID- 1502670 TI - [Organization of care in the house of the child]. PMID- 1502672 TI - [Music in the hospital]. PMID- 1502673 TI - [Genital anatomy and physiology of the young girl and the adolescent girl]. PMID- 1502674 TI - [Caring for an epileptic child]. PMID- 1502675 TI - [A severe malaise in infants]. PMID- 1502676 TI - [Gynecologic examination of children and adolescents]. PMID- 1502677 TI - Carl Langenbuch and the first cholecystectomy. PMID- 1502678 TI - Endoscopic drainage of pancreatic pseudocysts. AB - Seventeen patients with pancreatic pseudocysts were treated by endoscopic drainage. In nine cases we performed endoscopic retrograde pancreatic drainage (ERPD) by inserting 7-Fr pigtail catheters via the papilla into the cyst or into the main pancreatic duct. In two cases transduodenal cystotomy (ECD) and in eight cases transgastral cystotomy (ECG) are performed by using coagulator and papillotome. In five cases of ECG an endoprosthesis was inserted into the cyst. In two cases combination therapy of ERPD and ECG was performed. All patients reported reduction of continuous pain and postprandial epigastralgia after placement of endoprosthesis. After disappearance of symptoms and abnormal endoscopic findings within a period of 2-12 months the drainage tubes were removed. In one case postoperative dislocation of the prosthesis was observed; no serious complication was not encountered. The period of observation varied from 5 to 40 months. Two patients are presently under treatment with endoprostheses. Endoscopic drainage yielded good results in the treatment of pancreatic pseudocysts. PMID- 1502679 TI - Sclerotherapy of internal hemorrhoids using newly devised transparent disposable anorectoscope. AB - We devised a transparent anorectoscope for internal hemorrhoidal sclerotherapy. Using this scope the grade of hemorrhoids of the patients can be evaluated accurately through the transparent wall of the scope, and the device facilitates easier and safer sclerotherapy under clear direct vision, compared to the conventional free-hand-style treatment. We conclude that sclerotherapy using this anorectoscope represents a minimally invasive treatment for low-grade internal hemorrhoids and is recommendable for outpatient therapy of internal hemorrhoids. PMID- 1502680 TI - Pneumoperitoneum following percutaneous endoscopic gastrostomy. Does the timing of panendoscopy matter? AB - Percutaneous endoscopic gastrostomy (PEG) has had a significant impact on enteral alimentation in patients unable to maintain adequate oral caloric intake. PEG avoids the morbidity and mortality associated with the traditional feeding gastrostomies placed by celiotomy. Several authors have documented benign, self limiting pneumoperitoneum following PEG placement. No study has addressed whether the timing of panendoscopy in relation to gastric puncture has an effect on the incidence of post-PEG pneumoperitoneum. The authors prospectively studied 30 patients undergoing PEG. Panendoscopy was either performed before or after gastric puncture, and each patient then had abdominal radiographs to determine the presence of pneumoperitoneum. Four of 16 patients (25%) having panendoscopy prior to gastric puncture had radiographic evidence of pneumoperitoneum compared to three of 14 patients (23%) having panendoscopy following gastric puncture. The authors conclude that the timing of panendoscopy in relation to gastric puncture does not significantly effect the incidence of post-PEG pneumoperitoneum. PMID- 1502681 TI - Bioptic techniques in flexible endoscopy. An experimental study in the pig. AB - Low success rates in biopsies of submucosal gastric lesions have been reported. We undertook an experimental study in the pig of three different and commonly used bioptic techniques to test their ability to provide submucosal material using spiked as well as nonspiked biopsy forceps. The best results were obtained using the Crosta technique where the overlying mucosa is excised using a diathermy snare and biopsies are taken from the bared underlying tissue. The hole in-hole technique of Seifert and the ethanol injection technique of Asaki were inferior as to bioptic depth but not in size of the biopsies. Biopsy forceps with a central spike were slightly superior to those without. PMID- 1502683 TI - Thoracoscopic dissection of the esophagus. PMID- 1502682 TI - Pneumopericardium and subcutaneous emphysema of the neck. An unusual manifestation of colonoscopic perforation. AB - Subcutaneous neck emphysema has been reported infrequently following colonoscopic perforation and only a single case of pneumopericardium has been previously reported. The successful management of these patients in the literature has largely been non-operative. We report a case of colonoscopic perforation which presented with subcutaneous neck emphysema, pneumopericardium, and pneumoperitoneum that required operative intervention. PMID- 1502684 TI - Perforated synapses are present during synaptogenesis in rat neocortex. AB - It has been known for some time that perforated synapses increase in number and size with increasing age. Initially, these trends were used to support the concept that nonperforated synapses enlarge until an optimal size is reached, at which point they perforate and may subsequently split. More recent stereological and three-dimensional reconstruction investigations, however, suggest that this may not be the case and that perforated and nonperforated synapses constitute separate synaptic populations. In order to test the separate population hypothesis, synapses have been studied ultrastructurally in the parietal cortex of rats aged 19 and 20 days gestation, and 1 and 4 days postnatal. By examining synapses serially, and also by studying three-dimensional reconstructions, it has been demonstrated that perforated synapses are present at each of these ages. Some are relatively simple in organization, resembling previously described perforated synapses at 14 days of age, although others appear to consist of two or more separate PSD components. These findings demonstrate that perforated synapses are present from early on in synaptogenesis and that developing perforated synapses may have distinct characteristics that cast light on their developmental course. PMID- 1502685 TI - Effects of high-dose methamphetamine on monoamine uptake sites in rat brain measured by quantitative autoradiography. AB - The neurotoxicity of methamphetamine to monoaminergic neurons was examined. Neurotoxicity was assessed by quantitative autoradiography using radioligands specific for binding to norepinephrine, dopamine, and serotonin uptake sites. High-dose administration of methamphetamine led to decreases in binding to uptake sites for the three monoamines. Norepinephrine binding sites were decreased in certain amygdaloid nuclei and in the dorsomedial hypothalamic nucleus. Serotonin binding sites were reduced in widespread brain areas, while dopamine binding sites were reduced in the caudate putamen, olfactory tubercle, and nucleus accumbens. The decreases in binding site density for the three monoamines are limited to terminal field areas; cell body areas are not affected. Our results indicate that methamphetamine is neurotoxic to serotonin, dopamine, and norepinephrine neurons. The neurotoxicity to norepinephrine neurons is in selected brain areas. PMID- 1502686 TI - Aniracetam-evoked potentiation does not interact with long-term potentiation in the CA1 region of the hippocampus. PMID- 1502687 TI - Severe infantile sialidosis--the characteristics of oligosaccharides isolated from the urine and the abdominal ascites. AB - A female infant presenting congenital ascites, hepatosplenomegaly, coarse face, and delayed mental and physical development is described. Oligosaccharides in the urine and the abdominal ascites of this patient were investigated by Bio-Gel column chromatography. The level of urinary oligosaccharides excreted (nmol/mg creatinine) by the patient was 25.8 times the levels of the controls. The oligosaccharides in the urine and the ascites were composed almost entirely of sialyl oligosaccharides. The structures of urinary oligosaccharides were the same as those of oligosaccharides in the ascites. The ratio of high molecular weight sialyl oligosaccharides with repeating structures to low molecular weight sialyl oligosaccharides was higher in the ascites than in the urine. PMID- 1502688 TI - Pericentric inversion of chromosome 9 in prenatal diagnosis and infertility. AB - In order to evaluate the relation between pericentric inversion of chromosome 9 (inv(9)) and clinical problems, the characteristics of inv(9) were investigated on the basis of chromosomal analyses of fetuses and infertile couples. The incidence of such inversion in fetuses with parents having an offspring who suffered from various clinical problems was significantly higher than the basic incidence obtained in fetuses karyotyped by reason of advanced maternal age. In the chromosomal examination of the parents whose fetuses were diagnosed as inv(9), it was revealed that either parent might be the carrier. Furthermore, in the inv(9) carrying fetuses, the number of females was significantly greater than that of males. Analysis of infertile couples revealed that the incidence of such inversion in males was significantly higher than the basic incidence mentioned above. Moreover, infertile couples with an inv(9) carrier showed a significantly higher incidence of intrauterine fetal death, compared with infertile couples with a translocation carrier or those in which the etiology was unknown. These results indicate that inv(9) may often cause clinical problems in offspring of the carrier and infertility with unknown mechanisms related to sex. PMID- 1502689 TI - Role of norepinephrine in the lack of reflex tachycardia after angiotensin converting enzyme inhibitor treatment. AB - Angiotensin converting enzyme inhibitors decrease blood pressure without causing reflex tachycardia in hypertensives, but do not always do so in normotensives. To investigate this phenomenon, hemodynamic changes in normotensive rabbits receiving a subpressor dose of norepinephrine were studied following captopril or diltiazem treatment. We also investigated the effect of captopril on baroreceptor reflex in relation to norepinephrine infusion; the baroreflex sensitivity was determined by the relationship between mean arterial pressure and pulse interval receiving graded doses of phenylephrine. Captopril infusion decreased mean arterial pressure and pulse interval from 84 +/- 4 to 74 +/- 5 mmHg and 244 +/- 7.4 to 216 +/- 7.6 msec, respectively. In contrast, in rabbits receiving a norepinephrine infusion captopril lowered mean arterial pressure to the same extent (92 +/- 5 to 76 +/- 3 mmHg, p less than 0.05) without producing reflex tachycardia. When diltiazem was administered, reflex tachycardia occurred in rabbits both with and without a norepinephrine infusion. There was no difference in the baroreflex sensitivity between rabbits receiving norepinephrine with and without captopril treatment. However, the baroreflex curve showed a slight shift to lower pressures after norepinephrine infusion in the rabbits receiving captopril. These results suggest that elevating circulating norepinephrine might be involved in preventing reflex tachycardia after captopril. PMID- 1502690 TI - The microvasculature of the human bone marrow correlated with the distribution of hematopoietic cells. A computer-assisted three-dimensional reconstruction study. AB - Surgical specimens of ordinary bone marrow from eight patients were submitted to computer-assisted three-dimensional reconstruction from resin-embedded, semi-thin serial sections. This was undertaken with the aim of contributing to a better understanding of hematopoietic microenvironment by establishing the basic architecture of the bone marrow, particularly the microvasculature and its relation to the hematopoietic cell series. The basic vascular structure was found to consist of mutually intertwining sinuses and hematopoietic cords (or compartments), the latter with an arteriole running along the axis. This allowed to define the unitary structure of the bone marrow as a hematopoietic cord with a central arteriole and surrounded by sinuses. Here granulopoietic cells were distributed mostly along the wall of the central arteriole. Erythropoietic cells, located mainly around the sinus wall, proved to be forming a continuous network of cord instead of separate "islands" as usually assumed, justifying a designation of "erythroblastic cords". Megakaryocytes were positioned in close vicinity to the sinus wall. These findings appear not only to be helpful in analyzing factors involved in the in vivo hematopoiesis of man, but also to visualize the importance of structural studies of bone marrow. PMID- 1502691 TI - Acrosin profiles of human spermatozoa recovered from the new Sperm Prep II filtration column. AB - Twenty semen samples were collected and two aliquots of 1.5 ml were prepared from each sample. One sample of each pair (fraction-one) was used for evaluation of semen parameters and total acrosin activity of spermatozoa. The other sample of each pair (fraction-two) was mixed with an equal volume of Ham's F-10 medium and filtered through the Sperm Prep II. At the end of the filtration, the filtrate was pooled, sperm parameters were evaluated and total acrosin activity was assessed. Percentage of normal spermatozoa, sperm motility, and total acrosin activity of spermatozoa were significantly higher in the postfiltered fraction two than in the fresh fraction-one. Considering the great importance of acrosin for fertilization, it is suggested that Sperm Prep II filtration method may be beneficial in preparing spermatozoa from infertile men with low acrosin profiles for assisted reproduction programs. Further studies will be necessary, however, in order to confirm this, since the present study concerned men with known fertility. PMID- 1502692 TI - Comparison of characteristics between frequent participants and non-participants in screening program for stomach cancer. AB - To clarify the differences in characteristics between participants and non participants in the screening program for stomach cancer, life-style and medical histories were compared among 20, 169 subjects who lived in an urban area (Sendai) and a rural area (Wakuya and Tajiri) in Miyagi Prefecture, Japan. All subjects were classified into three groups according to the frequency of participation in the screening program during the last 5 years; i.e., frequent participating group (FPG) for 4 or 5 times, reference group (RG) for 1-3 times and non-participating group (NPG) for 0 times. Subjects in the FPG consumed more milk and green-yellow vegetable whereas those in the NPG consumed less these foods. The age-adjusted proportions of present smokers were higher in the NPG but lower in the FPG significantly. The proportions of subjects who had parental histories of all cancers and stomach cancer and past history of gastro-duodenal ulcer were higher in the FPG and lower in the NPG. To control influences among the variables a stepwise multiple regression analysis was done, and it revealed that smoking and parental history of cancers were strong predictors to explain the frequency of participation. PMID- 1502693 TI - Brunnstrom stages and Wallerian degenerations: a study using MRI. AB - We studied the relationship between the Brunnstrom stages obtained after rehabilitations and Wallerian degenerations detected by magnetic resonance imaging (MRI). Forty-nine hemiplegic patients were retrospectively studied. The patients were grouped into a low stage group (30 patients) demonstrating Brunnstrom stages I approximately IV and a high stage group (19 patients) demonstrating stages V approximately VI. MRI detected Wallerian degenerations as changes of signal intensity in corticospinal tracts on T2-weighted images. The signals were hypointense or hyperintense compared to the normal side according to the intervals between the MRI examinations and the ictuses. MRI showed Wallerian degenerations in 27 of 30 patients in the low stage group and 5 of 19 patients in the high stage group. The difference between the two groups was significant (p less than 0.005). PMID- 1502694 TI - Mortality among female practitioners of Chanoyu (Japanese "tea-ceremony"). AB - A cohort study aimed to evaluate the effect of drinking green tea on longevity was performed. Three thousand three hundred and eighty female practitioners of chanoyu (Japanese tea-ceremony), living in Tokyo, were followed from 1980 to 1988, and 280 were dead during this period. Standardized mortality ratios were estimated 0.55 when all Japanese women was used as standard population and 0.57 when women living in Tokyo was used, indicating the possibility that green tea is a protective factor for several fatal diseases. PMID- 1502695 TI - A physiologically based description of ethylene oxide dosimetry in the rat. AB - A physiologically based pharmacokinetic (PB-PK) model providing a quantitative description of ethylene oxide (ETO) dosimetry in the rat was developed by integrating information on physiology, tissue solubility of ETO, and rate constants for ETO metabolism and binding. The PB-PK model consisted of nine compartments; liver, lung, testis, brain, fat, venous blood, arterial blood, richly perfused and poorly perfused tissues. The tissue: air partition coefficients of ETO, determined by vial equilibration, were similar among the various tissues (range 44-83). The rate constants for glutathione (GSH) conjugation, hydrolysis, and hemoglobin (Hb)- and DNA-binding were estimated from published data and by conducting in vivo inhalation exposure studies. The model adequately predicted the concentrations of Hb and DNA adducts, hepatic and extrahepatic GSH, and urinary N-acetyl-S-(2-hydroxyethyl)-cysteine following inhalation exposures of 1.2 to 1,200 ppm and intravenous administration of 1 to 100 mg/kg of ETO in male Fischer-344 and Sprague-Dawley rats. There was no evidence of nonlinearity in the overall elimination of ETO in the dose range examined. However, nonlinearities in the components of this first order elimination process (namely GSH conjugation, hydrolysis, exhalation) were found to occur at high exposure concentrations. Characterization of the individual metabolic pathways that affect the tissue dosimetry of ETO is important for interspecies extrapolation and risk assessment for this chemical. PMID- 1502696 TI - On reference dose (RfD) and its underlying toxicity data base. AB - The toxicity data of pesticides were summarized and compared amongst different animal species and types of bioassays. These comparisons showed the expected inter-species and inter-bioassay variability. After quantitative and statistical analysis of these data, it was concluded that, on the average, a 2-year dog bioassay detected toxic responses at similar doses as a 2-year rat study, and that both of these bioassays detected toxic responses at lower doses than either a rat 2-generation bioassay, a rat developmental toxicity study, or a 2-year mouse bioassay. Although these chronic dog and rat bioassays were found to detect toxic responses at lower doses than the other studies listed, this analysis does not reflect the seriousness of the effects that were compared. Within the confines of this analysis, then, it appears that a 2-year dog and rat study, reproductive and developmental bioassays are a sufficient data base on which to estimate high confidence Reference Doses (RfDs), and furthermore, that an additional uncertainty factor is needed to estimate RfDs to account for this inter-species and inter-bioassay variability when fewer than this number of bioassays are available. PMID- 1502697 TI - Effects of hexachloro-1,3- butadiene and 1,1,2,2- tetrachloroethylene on individual serum bile acids. AB - Rats were exposed to hexachlorobutadiene (HCBD) or tetrachloroethylene (TET) in order to determine which of these chemicals was more likely to be responsible for elevations in individual serum bile acids (SBA) found in workers exposed primarily to these two chemicals. Increases in cholic and taurocholic acids were found on exposure to high doses of HCBD. Elevations of SBA occurred right down to low exposures for TET, however, with cholic, chenodeoxycholic, and glycocholic acids being the most sensitive bile acids. Only at high doses for each chemical was there any indication of liver injury as determined by routinely used parameters such as serum enzymes or bilirubin. The data suggest that TET is likely to play a role in the elevated individual SBA in an exposure situation where both this chemical and HCBD are found. PMID- 1502698 TI - The U.S. Environmental Protection Agency's Risk Assessment Guidelines: current status and future directions. PMID- 1502699 TI - Human exposure to benzo(a)pyrene:some more of the story. PMID- 1502700 TI - Human immunodeficiency virus (HIV)-indeterminate western blots and latent HIV infection. PMID- 1502701 TI - Activation during preparation and storage of platelet concentrates. PMID- 1502702 TI - Resolution of infection status of human immunodeficiency virus (HIV) seroindeterminate donors and high-risk seronegative individuals with polymerase chain reaction and virus culture: absence of persistent silent HIV type 1 infection in a high-prevalence area. AB - To address concerns over the prevalence of silent (antibody-negative) infections among blood donors and high-risk populations, a combination of proviral amplification by polymerase chain reaction (PCR) and viral isolation by co culture techniques was employed to resolve the human immunodeficiency virus type 1 (HIV-1) infection status of well-characterized groups of suspect blood donors and others identified in the blood bank setting. No silent infections were found in 65 follow-up samples from 26 persistently HIV-1-seroindeterminate blood donors, 16 persistently seronegative heterosexual partners of infected transfusion recipients, and 6 high-risk seronegative homosexual men identified through donor look-back investigations. In contrast, 21 seropositive controls tested positive. These results suggest a low prevalence of persistently silent infections in at-risk populations, even in high HIV prevalence regions. The PCR assay, with a co-detected internal positive control, and appropriate confirmatory algorithms, was found to be a useful direct assay to rule out infection, especially in concert with confirmatory virus isolation. PMID- 1502703 TI - Absence of human T-lymphotropic virus types I and II infection in an Ontario hemophilia population. AB - Two hundred ninety-three serum samples from Ontario hemophiliacs and 200 samples from human immunodeficiency virus-positive blood donors were screened for the presence of antibodies to human T-lymphotropic virus type I (HTLV-I) by enzyme linked immunosorbent assay, radioimmunoassay, and Western blot techniques. None of the serum samples provided unequivocal positive results, but several samples gave inconclusive results. Of the hemophiliacs with inconclusive serologic results from whom peripheral blood lymphocyte DNA could be obtained, all were negative for HTLV-I and HTLV type II (HTLV-II) sequences as determined by polymerase chain reaction (PCR). PCR was also performed on a lymph node biopsy sample taken from a hemophiliac who developed a rare T-cell lymphoma; the sample was negative for HTLV-I and -II sequences. These results indicate that Ontario hemophiliacs have not been exposed to HTLV-I or HTLV-II. PMID- 1502704 TI - A clinical and immunologic study of blood transfusion and postoperative bacterial infection in spinal surgery. AB - Allogeneic blood transfusion has been implicated as an independent risk factor for postoperative bacterial infection in clinical and animal studies. The association among transfusion, quantitative immunologic factors, and infection was examined in 102 patients undergoing 109 spinal fusion procedures. In 60 procedures, patients received autologous blood only; in 24 procedures, they received at least 1 unit of allogeneic blood, and in 25 procedures, they received no transfusions. Twenty-two patients developed bacterial infections, in 8 cases while in hospital and in 14 cases after discharge. Univariate analysis revealed that patients who received any allogeneic blood and those who received no allogeneic blood differed significantly in the rate of hospital-acquired infection (20.8 vs. 3.5%), length of stay (12.3 vs. 9.7 days), days of fever greater than or equal to 38 degrees C (4.0 vs. 2.9), days on antibiotics (3.9 vs. 2.5), duration of surgery (309 vs. 231 min), blood loss (1343 vs. 887 mL), surgeon, and postoperative drop in natural killer (NK) cells (-174 vs. 42/microL). Multivariate logistic and linear regressions revealed that the number of allogeneic units transfused was the only significant predictor of in-hospital infection (p = 0.016) or days on antibiotics and length of stay. None of the clinical, surgical, or transfusion variables was significantly associated with posthospital infection, although a significantly greater drop in NK cells had occurred in patients who developed infection (p = 0.0035). These data strongly implicate allogeneic transfusion as a risk factor for in-hospital postoperative bacterial infection.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1502705 TI - The effect of prestorage irradiation on posttransfusion red cell survival. AB - Transfusion-associated graft-versus-host disease (TA-GVHD) may occur whenever immunologically competent allogeneic lymphocytes are transfused to an immunocompromised recipient. Irradiation of blood components eliminates the risk of TA-GVHD but may damage the cellular elements in the transfused component, particularly if the cells are stored for prolonged periods in the irradiated state. To study the effect of irradiation on long-term storage of red cells, AS-1 red cells from eight normal subjects were prepared on two occasions. On one occasion, the units were stored as standard AS-1 red cells for 42 days at 4 degrees C; on the other, they were exposed to 3000 cGy radiation within 4 hours of collection and then were stored as AS-1 red cells for 42 days at 4 degrees C. The donations were at least 12 weeks apart. Irradiated units demonstrated significant elevations in poststorage plasma hemoglobin (Hb) (623 +/- 206 vs. 429 +/- 194 g/dL [6230 +/- 2060 vs. 4290 +/- 1940 g/L], p less than 0.02) and plasma potassium (78 +/- 4 vs. 43 +/- 9 mEq/L [78 +/- 4 vs. 43 +/- 9 mmol/L], p less than 0.01) and significant decreases in red cell ATP (1.9 +/- 0.2 vs. 2.1 +/- 0.3 microM/g Hb, p less than 0.04) and 24-hour posttransfusion red cell recovery (68.5 vs. 78.4%, p less than 0.02), as compared to nonirradiated units. It can be concluded that irradiation with 3000 cGy damages red cells and that long-term storage in the irradiated state may enhance this damage. Red cells should not be stored for 42 days after irradiation with 3000 cGy. PMID- 1502706 TI - Detection of plasmapheresis-induced platelet activation using monoclonal antibodies. AB - Twelve volunteer plasma donors were studied so as to determine the extent and duration of in vivo platelet activation caused by automated plasmapheresis. Samples obtained immediately before and after donation were mixed with murine monoclonal antibodies PAC-1 and S12, which bind specifically to activated platelets. Antibody binding on platelets was quantitated by flow cytometry. The change in the mean fluorescence intensity (MFI) (MFI after donation minus MFI before donation) was 61 +/- 23 (confidence interval [CI], 48-75) for PAC-1 and 56 +/- 64 (CI, 19-92) for S12 in plasmapheresis donors, as compared to 0.3 +/- 0.8 (PAC-1; CI, -0.2-0.8) and 0.3 +/- 0.9 (S12: CI, -0.3-0.9) in whole blood donors (p less than 0.05). Additional studies showed circulating activated platelets up to 48 hours after plasmapheresis. In contrast to other data, significant platelet activation was demonstrated following plasmapheresis on an automated machine. None of the donors had clinical complications. Nevertheless, it may be appropriate to delay subsequent plasmapheresis and platelet procurement from such donors until evidence of platelet activation has disappeared. PMID- 1502707 TI - Virus sterilization in platelet concentrates with psoralen and ultraviolet A light in the presence of quenchers. AB - The virucidal and functional effect of the treatment of platelet concentrates (PCs) with long-wave ultraviolet light (UVA) and the psoralen derivative 4' aminomethyl-4,5',8-trimethylpsoralen (AMT) was studied. Cell-free vesicular stomatitis virus (VSV) was completely inactivated (greater than or equal to 6.5 log10) on treatment of PCs with 25 micrograms per mL (85 microM) of AMT and with 20.7 J per cm2 (30 min) of UVA in the presence of air, or with 82.8 J per cm2 (2 hours) of UVA under conditions of reduced oxygen tension. When treatment was in air, the extent and rate of platelet aggregation in response to collagen measured after overnight storage were reduced to about 70 and 50 percent of control values, respectively; however, aggregation responses were similar to those of controls when PCs were treated under reduced oxygen tension. As a means of eliminating the necessity of oxygen depletion during AMT and UVA treatment, we examined the effects of the addition of quenchers of reactive oxygen species. The presence of 2 mM (2 mmol/L) mannitol during treatment of PCs with 25 micrograms per mL of AMT and 20.7 J per cm2 of UVA in air significantly improved the aggregation response and other in vitro indicators of platelet function and had little or no effect on VSV inactivation. Less benefit was observed with the other quenchers examined. Thus, the nucleic acid specificity of psoralen photoinactivation under reduced oxygen conditions may also be attainable when selected free radical scavengers such as mannitol are present during treatment in air. PMID- 1502708 TI - Detection of cell-drug (hapten)-antibody complexes by the gel test. AB - Most drugs causing immunocytopenias do not bind firmly to the affected cells. Consequently, the drug-dependent antibodies in such cases are completely removed from their binding sites by conventional cell washing. It has recently been shown that such cell-drug-antibody complexes do survive the washing procedure, if the drug (metabolite) was included in the wash medium. The study reported here used the microtube gel test to reexamine the reactivity of different drug-dependent red cell antibodies: cefotaxime (n = 1), carbimazole (n = 1), cianidanol (n = 1), diclofenac (n = 3), penicillin (n = 3), and nomifensine (n = 10). Whether the drug tested binds (penicillin, cianidanol, carbimazole, and diclofenac) or does not bind (cefotaxime and nomifensine) firmly to the cells, the resultant cell drug-antibody complex could be recognized on and/or in the gel after it was separated from the mixture containing the drug by means of centrifugation alone and without washing. It is concluded that the gel test might be of value not only for the detection of drug-dependent antibodies, but also for the analysis of subtle drug--cell interactions. PMID- 1502709 TI - Biocompatibility of white cell filters as evaluated by complement activation. AB - The biocompatibility of nine different white cell filters was examined by analysis of complement activation in plasma specimens obtained from blood components before and after filtration. Filters for both red cell (RBC) concentrates and platelet concentrates (PCs) were tested. It was found in all of the filters tested that the postfiltration levels of complement activation products were not higher than the prefiltration levels in RBC concentrates and PCs. One exception was the filtration of multiple PCs with Imugard IG-500, in which case a rise in C3 activation products was seen. Moreover, there was a significant rise in C3 activation products, but not the terminal complement complex, when plasma was filtered through Imugard E, which contrasted with results with the other filters. High initial and storage time-dependent levels, especially of C3 activation products, were observed in the PCs, probably due to their processing at room temperature. It can be concluded that the majority of the filters tested do not activate complement. PMID- 1502710 TI - Improvement in appropriate autologous donations with local education: 1987 to 1989. AB - Preoperative autologous blood donation for elective surgery patients at university hospitals was underused in the past. More recently, national educational efforts have been made. To test the impact of local surgeon interviews and education, in 1988 the same local educational program was instituted at three university hospitals; three community hospitals were used as controls. Donation by appropriate patients of interviewed surgeons (elective surgery, crossmatch recommended, no contraindications to donation) increased from 24 percent (44/180) to 40 percent (88/222) (p = 0.002) and 15 percent (21/143) to 32 percent (41/127) (p = 0.001) at two university hospitals where the investigator-educators were on site, but not at the three community hospitals. Between 1987 and 1989, donation rates at all six hospitals remained low among patients for whom autologous donation was (probably) less appropriate. Donation rates for type and screen procedures were 3.0 percent (131/4587) in 1987 and 3.0 percent (199/6606) in 1989 (p = 0.67). Donation rates for "no blood order" procedures were 0.2 percent (15/9429) in 1987 and 0.1 percent (9/11,239) in 1989 (p = 0.14). It can be concluded that appropriate autologous blood donations increased at university hospitals where surgeons were individually interviewed and educated by an investigator on site. However, despite this increase, apparently eligible elective surgery patients in 1989 still failed to donate. This situation deserves additional investigation. PMID- 1502711 TI - Validation of a simple method to count very low white cell concentrations in filtered red cells or platelets. AB - The increased performance of white cell (WBC) filters makes it difficult to count precisely the number of residual WBCs. Concentrations as low as 0.01 WBC per microL cannot be determined with electronic cell counters, conventional hemocytometers, or the flow cytometric techniques currently being used. This article describes a simple, manual method using a Nageotte hemocytometer with a large-volume chamber (50 microL) to count the number of WBCs contained in red cell (RBC) suspensions (preparations A, B, and C) and in platelet suspensions (preparation D) diluted 1 in 10 pure, or concentrated two fold. To validate the method, several reference ranges, prepared by successively adding mononuclear cells to a suspension of pure RBCs or platelets, were used. Among the different series, validation ranges varied from 0.2 to 12 to 0.01 to 0.5 WBCs per microL and correlation coefficients ranged from 0.929 to 0.996. To determine the limit of accurate detection, accuracy tests (n = 160) were carried out by two experienced operators on samples with WBC concentrations of about 5, 10, and 120 times the concentration at the theoretical limit of detection (1 WBC/chamber). No significant difference was observed in the various types of preparations (A, B, C, D) in the tests performed by the two operators. However, intra-assay coefficients of variation were 18, 9.5, and 2.2 percent, respectively, at WBC concentrations of 5, 10, and 120 times that at the theoretical limit of detection. These observations show that a limit of accurate detection (10%) seems to be reached when 10 cells are observed in a Nageotte hemocytometer.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1502712 TI - Anti-i causing acute hemolysis following a negative immediate-spin crossmatch. AB - A unique case of acute hemolysis following transfusion of red cells (RBCs) that were found compatible by immediate-spin (IS) crossmatch technique is reported. Screening tests for unexpected antibodies, using low-ionic-strength saline (LISS), 10 minutes' incubation at 37 degrees C, and anti-IgG, were nonreactive; however, 1 transfused unit was found crossmatch incompatible by indirect antiglobulin technique (IAT). An anti-i (titer 512 at 4 degrees C) that was not an autoantibody was identified in the patient's serum. Unlike the incriminated donor RBCs, most I+ RBCs did not react by LISS-IAT. Variable reactivity was seen with ficin-treated I+ RBCs, and there was marked hemolysis of iadult and icord RBCs. In marked contrast, dominant Lu(a-b-) RBCs, with reduced expression of i, did not react by any test method; nor did autologous I+, Lu(b+) RBCs. The in vivo clinical significance of this anti-i was confirmed by monocyte monolayer assay and RBC survival studies. The patient's i antigen may have been altered, by either chemotherapy or disease, and lacked part of the i antigen-mosaic. Her antibody was directed at epitopes of i that were absent from her RBCs. Those i epitopes missing from her RBCs are also absent on dominant Lu(a-b-) RBCs. This anti-i represents a unique cause of an acute hemolytic transfusion reaction. It also represents a case of acute immune-mediated hemolysis following transfusion of IS crossmatch-compatible blood when screening tests for unexpected antibodies are nonreactive. Because of the rarity of such cases (less than 1/200,000 RBC units transfused), modifications to pretransfusion testing protocols are not proposed. PMID- 1502713 TI - Severe anaphylactic reactions following transfusions of platelets to a patient with anti-Ch. AB - The high-frequency Chido (Ch) antigen, found predominantly in plasma, is a determinant of the C4d fragment of the C4 molecule and is acquired by red cells during in vivo complement activation. Antibodies are made by Ch- people who lack C4S. It has often been reported that anti-Ch (and anti-Rg) do not cause hemolytic transfusion reactions. Reported here is a case of a transfusion reaction caused by anti-Ch. The antibody did not cause red cell destruction, but did cause a life threatening anaphylactic reaction during transfusion of plasma proteins in pooled platelets. The antibody was of the IgG4 subclass and might have caused a short term, sensitizing anaphylactic response. This case, and one previously reported in which a patient with anti-Rg experienced a severe reaction to fresh-frozen plasma and a plasma derivative, illustrates that these antibodies can cause severe, life-threatening reactions in patients who receive plasma-containing components. PMID- 1502714 TI - Antithrombin III: physiology, deficiency, and replacement therapy. PMID- 1502715 TI - Transfusion-related acute lung injury: a neglected, serious complication of hemotherapy. PMID- 1502716 TI - Absence of antibodies to HTLV-I in Northern Marianas blood donors. PMID- 1502717 TI - Standard terminology for weak D antigens. PMID- 1502718 TI - Is the febrile response to transfusion due to donor or recipient cytokine? PMID- 1502719 TI - Understanding liposomal properties to aid their clinical usage. PMID- 1502720 TI - A transcription factor (?) joins the SH2 crowd. PMID- 1502721 TI - Are molecular filters really necessary? PMID- 1502722 TI - A family of DNA virus genes that consists of fused portions of unrelated cellular genes. PMID- 1502723 TI - Glutamyl-transfer RNA: a precursor of heme and chlorophyll biosynthesis. AB - In green plants, archaebacteria and many eubacteria, the porphyrin ring that is common to both chlorophyll and heme is synthesized from 5-aminolevulinic acid (ALA) via an interesting pathway. This two-step process involves the unusual enzymes glutamyl-tRNA reductase and glutamate-1-semialdehyde 2,1-aminomutase. Interest in this pathway has increased since it was discovered that a tRNA cofactor was required for the formation of ALA. This tRNA(Glu) is common to the biosyntheses of both porphyrins and proteins. PMID- 1502724 TI - Bacterial protein translocation: kinetic and thermodynamic role of ATP and the protonmotive force. AB - The energetic mechanism of preprotein export in Escherichia coli has been a source of controversy for many years. In vitro studies of translocation reactions that use purified soluble and membrane components have not clarified the main features of this mechanism. Translocation occurs through consecutive steps which each have distinct energy requirements. Initiation of translocation requires ATP and the SecA protein. Most of the further steps can be driven by the protonmotive force (delta p). PMID- 1502725 TI - Packaging and unpackaging the sea urchin sperm genome. AB - Two species of histones in sea urchin sperm (Sp H1 and Sp H2B) are chimeric molecules whose highly basic amino-terminal domains are dephosphorylated at the last stage of sperm cell differentiation, and rephosphorylated immediately following fertilization. The phosphorylated regions consist largely of repeating tetrapeptides with two basic residues flanking Ser-Pro residues ('SPKK' motifs) and are predicted to have beta-turn secondary structures. Alteration of the charge and structure of the SPKK sites may play a role in the unusually dense DNA packaging of the mature sperm chromatin. The motif resembles the target site of cell-cycle-associated cdc2 kinases and is found in several other proteins whose nucleic acid affinities may be altered during the cell cycle. PMID- 1502726 TI - Experimental determination of DNA helical repeats. PMID- 1502727 TI - The ets gene family. AB - Ets proteins have a conserved DNA-binding domain and regulate transcriptional initiation from a variety of cellular and viral gene promoter and enhancer elements. Some members of the Ets family, Ets-1 and Ets-2, cooperate in transcription with the AP-1 transcription factor, the product of the proto oncogene families, fos and jun, while others, Elk-1 and SAP-1, form ternary complexes with the serum response factor (SRF). Certain ets gene family members possess transforming activity while others are activated by proviral integration in erythroleukaemias. PMID- 1502728 TI - Ribotoxin recognition of ribosomal RNA and a proposal for the mechanism of translocation. AB - The ribotoxins alpha-sarcin and ricin catalyse covalent modifications in adjacent nucleotides in 28S rRNA, yet the elements of nucleic acid structure that they recognize are not only different but incompatible. This suggests that this ribosomal domain (which in two dimensions is a seven-base-pair helical stem and a 17-member single-stranded loop) has alternate conformers. Since the domain is involved in binding of aminoacyl-tRNA and GTP hydrolysis, we propose that the switch between the two configurations, perhaps initiated by the binding of elongation factors, plays a role in translocation. PMID- 1502729 TI - [Morphofunctional features of the nucleoli in glandular hyperplasia and endometrial cancer]. AB - The morphofunctional peculiarities of epithelial cells nucleoli in patients with glandular hyperplasia and endometrial cancer has been studied on the cytological smears from endometrium stained with silver nitrate were investigated. The patterns of nucleolonemic nucleoli content and high activity of nucleolar organizers in cancer of corpus uteri are revealed. PMID- 1502730 TI - [Estimation of combining ability of specialized types of the Big White breeds]. AB - The combining ability of the specialized intrabreed types of Estonia Big White (EBW-1) and Ukrainian Big White (UBW) breeding of pigs has been studied by the results of their productivity using the first Griffing method (1956). A close coincidence of theoretical and practical indices by the studied sings, proves the ability to use this method for prediction of interline hybridization of pigs. PMID- 1502731 TI - [Comparative analysis of variability of various genetic systems in farm animals]. AB - The particularities of the genetic structure formings of the different genetic systems (biochemical and immunogenetic markers) in the breeds, interbreed crosses of sheep and groups of cattle in connections with the locus, breed and the way of the productivity trait selections were described. The uniqueness of the characteristics and forming mechanisms of the genetic structure related with these factors and the inadequacy of the suppositions about them on the genealogical data were discussed. PMID- 1502732 TI - [Genetic interrelationship between lactation maturity, fertility and life productivity in Simmental cows]. AB - In Ukrainian simmental heritabilities of maturity rate defined as ratio of the highest to first lactation yields were 0.17. Single lactation production and longevity are negatively correlated (-0.45). Waiting for third lactation records of test daughters and including secondary trains like reproduction or persistency into selection should slow down or stop the decrease. PMID- 1502733 TI - [Genotoxicity of the preparation "binase" in tests on Salmonella: Ames test and ARA-test]. AB - The present work deals with mutagenicity determination of enzyme sample "binase" (Bacillus intermedius ribonuclease) in microbial test-systems: Ames test and Ara test. The weak mutagenic effect of "binase" high concentration was established in both tests by induction of forward Ara-mutations and Histidine-reverse mutations. A metabolic activation is seen to remove this effect. PMID- 1502734 TI - [Clinico-genetic aspects of the ovarian failure syndrome]. AB - Clinical-genetic examination of 50 patients with menopause praecox syndrome has been performed. The results of the examination show genetic syndrome heterogeneity. Chromosomal and gene mutations take part in the syndrome pathogenesis. Chromosomal abnormalities frequency is 12%. Chromosomal aberrations are presented by different mosaicism types of sex chromosomes. Monogenic syndrome genesis with different inheritance types of the pathologic gene is determined: autosomal-recessive or autosomal-dominant. PMID- 1502735 TI - [Chromosome abnormalities of human gametes and intrauterine selection. Male gametes]. AB - Man appears to be unique among mammals with respect to very high level of reproductive wastage. It seems reasonable to suppose that many early losses attribute to cytogenetical abnormalities. However, this stage of pregnancy is difficult to be studied. The investigation of gametes is one of the most reliable ways to estimate the cytogenetical disorders in early life. The results from cytogenetical analysis of human male gametes are summarized. PMID- 1502736 TI - Anemone cell tumor revisited. PMID- 1502737 TI - Identification of Charcot-Leyden crystals by electron microscopy. AB - Observations of the ultrastructure of Charcot-Leyden crystals are sporadic in the literature. These crystals appear occasionally in clinical materials, however, and may pose diagnostic dilemmas if not correctly identified. Two cases in which unusual crystallike structures were seen on electron micrographs of specimens were evaluated for diagnostic purposes. These structures were tentatively identified as Charcot-Leyden crystals and subsequently were confirmed as such by immunoperoxidase labeling. The cases are reported together with a review of the ultrastructure, histology, immunology, and natural history of Charcot-Leyden crystals. PMID- 1502738 TI - Birbeck granules or Birbeck junctions? Intercellular "zipperlike" lattice junctions in eosinophilic granuloma of bone. AB - Three cases of eosinophilic granuloma of bone exhibited intercellular attachments between histiocytes, with a pentalaminar structure identical to that seen in nearby intracellular Birbeck granules (BG). It is proposed that the term "lattice junction" be coined to describe this organelle, which seems to be expressed only by cells of monocytic-histiocytic lineage. While this finding confirms the ability of the surface membrane to form such structures, it does not necessarily preclude other intracytoplasmic sites of origin for some BG. The previously suggested role of BG in membrane storage and regulation is reiterated as a supportable model for their function. PMID- 1502739 TI - Ovarian myxoma: ultrastructural and immunohistochemical findings. AB - The ultrastructural and immunohistochemical findings are reported in two ovarian myxomas, one of which was also associated with a sclerosing stromal tumor of the same ovary. Both neoplasms showed a myxoid, moderately cellular proliferation of spindle and stellate cells interspersed with areas of fibrosis and hemorrhage as well as delicate vascular spaces. Ultrastructurally, stellate neoplastic cells with irregular nuclei and occasional nucleoli were embedded in a mucinous and loose collagen matrix. Their cytoplasm showed abundant intracytoplasmic thin filaments that rarely condensed into poorly formed dense bodies. These thin filaments correlated with immunoreactivity for muscle-specific actin and vimentin. The neoplastic cells showed no immunoreactivity with antibodies to desmin, S-100 protein, cytokeratin AE1:AE3, factor VIII-related protein, or placental alkaline phosphatase. These ultrastructural and immunohistochemical findings are consistent with myofibroblastic differentiation. These ancillary studies exclude important, clinically more aggressive differential considerations such as myxoid rhabdomyosarcoma, myxoid liposarcoma, myxoid neural tumors, mucinous adenocarcinoma showing pseudomyxomatous change, and myxoid-appearing endodermal sinus (yolk sac) tumor. PMID- 1502740 TI - A fast method for processing biologic material for electron microscopic diagnosis in infectious disease. AB - A fast method for processing biologic material for electron microscopy for precise and specific diagnosis of infectious agents is an increasing necessity. After different, reportedly fast methods were tested, a useful and quick technique was developed that provides well-preserved cellular structures, enabling the etiologic diagnosis of infectious agents even in necrotic tissue or other biologic material such as sputum, bronchoalveolar lavage, and the like. This procedure takes less than 3 hours. PMID- 1502741 TI - Continent urinary diversion using cutaneous ileocecocystoplasty. AB - We have employed a technique of continent urinary diversion that uses ileocecocystoplasty to incorporate native bladder into the urinary reservoir. This allows creation of a reservoir in selected patients using less complicated surgery than complete replacement of the bladder and avoids ureteral-intestinal anastomoses. Early results are promising for this simplified means of continent diversion. PMID- 1502742 TI - Comparison of plicated and stapled continent ileocecal stoma. AB - Tapered terminal ileum and an intact ileocecal valve have been shown to be an effective efferent continence mechanism in patients with continent ileocecal urinary reservoirs. The terminal ileum can be tapered by simple suture plication or with linear gastrointestinal stapling devices. We used precise urodynamic techniques to study 21 continent urinary reservoirs constructed from ileocecal bowel segments: 14 with plicated segments and 7 with stapled segments. Mean contraction pressures tended to be higher in the latter (P = 0.054), although maximum contraction pressures were similar (P = 0.48). Terminal ileum tapered with the gastrointestinal stapling device and an intact ileocecal valve provide for an effective efferent continence mechanism that is easy to construct and catheterize. PMID- 1502743 TI - Surgical management of urethral strictures based on etiology. Where do urethral stents fit in? AB - Recent studies in the urologic literature indicate a renewed interest in the management of urethral stricture disease. Specifically, urologists are now treating all types of urethral strictures regardless of location, etiology, or extent with methods other than primary urethroplasty or direct vision internal urethrotomy (DVIU), i.e., balloon dilation or urethral stenting. To see which patients might best be managed by these new modalities, we reviewed our experience with urethral strictures at LAC-USC Medical Center. PMID- 1502744 TI - Specific investigations in chronic urinary bilharziasis. AB - Seventy-two patients with histologically confirmed chronic urinary bilharziasis were studied for the reliability of some specific investigative tools in diagnosing this disease, namely urinalysis, serology, urography, and cystoscopy. Of the 72 patients 36 (50%) had hematuria and only 3 (4%) had ova of Schistosoma haematobium on urinalysis. Sixty-two patients (86%) had features of bilharziasis on intravenous urography (IVU). Of the remaining 10 patients with negative urography 6 underwent serology and all had positive results. Of the total patients 52 underwent serology and 49 had significant bilharzial antibody titer (94.2%). At cystoscopy all patients (100%) had features of bilharziasis. It is concluded that the most reliable diagnostic tools in chronic urinary bilharziasis are cystoscopy, serology, and to a lesser extent urography. Unlike early bilharziasis, chronic bilharziasis can be missed if total reliance is placed on urinalysis for screening a population at risk. PMID- 1502746 TI - Renal artery aneurysms. AB - Renal artery aneurysms, previously considered to be rare, have been diagnosed more frequently in recent years mainly due to the extensive use of angiography. Fifty-six patients with 67 aneurysms were evaluated, 5 of these were dissecting aneurysms. Most cases were manifestations of medial hyperplasia or atherosclerosis of the renal arteries. Symptomatology is not pathognomonic. Expanding aneurysm, intractable hypertension, hematuria, and renal infarction represent the most common indications for surgical repair. Reconstruction and repair of these aneurysms, with preservation of the kidney, is the preferred treatment. Surgery was performed on 17 patients (30%): 14 patients had primary repair, while 3 patients underwent nephrectomy for associated carcinoma and end stage kidney disease. Temporary occlusion of the renal artery with hypothermic perfusion allows surgical repair safely to both patient and kidney. Autotransplantation into the ipsilateral iliac fossa was employed for dissecting aneurysms after resection and repair of the diseased segment. Nine of 12 hypertensive patients required no treatment for hypertension following aneurysmal repair, while 3 patients had improved control. PMID- 1502745 TI - Transurethral resection of prostate under TV monitoring (TV-TURP). AB - Since February 1987, we have used television monitoring as the main method for operative guidance during transurethral resection (TV-TURP). With this system, the surgeon watches the image on the TV monitor during TURP, and does not look through an endoscope. Seventy-one cases treated using TV-TURP were compared with 50 cases treated by conventional TURP without TV monitoring. The resection time per gram of tissue for TV-TURP was not significantly different from that of the conventional TURP. The other resulting data for TV-TURP were also statistically similar to those for conventional TURP. TV-TURP is an excellent method and not inferior to conventional TURP. PMID- 1502747 TI - Retrospective review of sexual and marital satisfaction of spinal cord injury and diabetic males post penile injection or implant. AB - This study compares sexual activity and sexual and marital satisfaction in spinal cord-injured (SCI) and diabetic men who had received either a penile prosthesis or papaverine/phentolamine injections for the treatment of impotence. Questionnaires were used retrospectively to assess changes pre- and post procedure in 30 SCI and 26 diabetic males. Regardless of whether they received a penile prosthesis or injections, both diabetic and SCI males reported increases in diversity and frequency of sexual activities and satisfaction with sexual activities post-implant/injection. When compared with a normative sample, both diabetic and SCI males were found to have poorer body image post implant/injection. They also reported more disagreement with their partners but engaged in more activities together. PMID- 1502748 TI - Extracorporeal shock-wave lithotripsy (ESWL) monotherapy for stones in lower ureter. AB - Extracorporeal shock-wave lithotripsy (ESWL) has been accepted as the method of choice for most upper urinary tract calculi. However, in cases of stones in the lower ureter, ureteroscopic procedures have generally been preferred. Using the Dornier HM3 lithotriptor with modifications in the patient's position, we were able to successfully treat 155 unselected cases of lower ureteral calculi. The average stone size was 9.6 mm (range 5-23 mm). One hundred forty-three patients had stones located below the lower margin of the sacroiliac joint. These patients were placed in a supine position. The stones were visualized radiologically without use of a ureteral catheter in 78 percent of the patients; in 22 percent a ureteral catheter was inserted prior to ESWL to aid in stone localization. In 145 patients (94%) treatment was completed in one session; 10 patients (6%) required two sessions. Of the patients, 38 percent were free of stones one day after ESWL; 97 percent became stone free within three months, and only 3 patients required endoscopic manipulation, after ESWL. Twelve patients had stones in the midureter overlying the sacroileum. They were placed in the prone position, and the calculi were visualized with the aid of a ureteral catheter. All these patients became free of stones one month after treatment. There were no significant treatment related complications except for bacteremia in 1 case. In view of the remarkable efficacy, negligible complication rate, and shorter hospital stay as compared to ureteroscopic stone manipulations, we recommend high energy ESWL as the primary monotherapy of mid and lower ureteral stones. PMID- 1502749 TI - Management of urinary tract in children with epidermolysis bullosa. AB - Epidermolysis bullosa is a group of rare genetic disorders characterized by noninflammatory blistering lesions of the skin occurring after minor mechanical trauma. In association with junctional epidermolysis bullosa, a syndrome of pyloric atresia has occasionally been noted in the literature. Several infants who had this combined disorder have been reported to have severe genitourinary tract involvement. Most of these patients have died at an early age because of severe urinary tract involvement. We describe a rare survivor who was initially treated with urinary diversion. Subsequent attempts at undiversion of this patient were unsuccessful. He is presently stable following rediversion. The entities of e. bullosa and e. bullosa/pyloric atresia are reviewed with emphasis on urologic associations. PMID- 1502750 TI - Tethered cord syndrome: cause for urge incontinence and pain in lower extremities. AB - An eight-year-old girl has had urge incontinence for the last three years and muscle weakness and pain in the lower extremities for one month. Urodynamic study revealed a bladder instability of severe degree. Tethered cord syndrome caused by a tight filum terminale was identified by metrizamide myelography. An untethering of the filum terminale resolved her symptomatology completely. The urologist should be aware of this syndrome in a patient presenting with incontinence that has persisted for a long time or has recurred. PMID- 1502751 TI - Abdominoscrotal hydrocele: diagnosis by herniogram and ultrasound. AB - A four-month-old male infant presented with a lower abdominal mass and bilateral hydroceles. With pressing on the abdominal mass, the right hydrocele became larger. Herniogram and ultrasound led to the diagnosis of abdominoscrotal hydrocele which was successfully repaired through an extraperitoneal and intraperitoneal approach. PMID- 1502752 TI - Milk of calcium renal cyst: CT findings. AB - Milk of calcium in the kidney is usually found in association with hydronephrosis or caliceal diverticula. A case of milk of calcium in a renal cyst is presented. Contiguity with an adjacent rib can make it difficult to detect the dependent layered milk of calcium. PMID- 1502753 TI - Use of gadolinium-DTPA-enhanced MRI to characterize renal mass in patient with renal insufficiency. AB - A patient with chronic renal insufficiency was found to have an indeterminate renal mass after renal ultrasound, non-contrast CT, and non-contrast MRI studies. The mass was correctly diagnosed as an enhancing tumor with gadolinium-DTPA enhanced magnetic resonance imaging. PMID- 1502754 TI - A seventy-six-year-old man with mild azotemia. PMID- 1502755 TI - Hoarseness; a unique clinical presentation for renal cell carcinoma. AB - The first reported case of an isolated metastasis to the larynx from a regionally localized renal cell carcinoma presenting clinically as hoarseness is discussed. Aggressive management and outcome are presented. PMID- 1502757 TI - Renal leiomyosarcoma: plea for aggressive therapy. AB - We report a case of renal leiomyosarcoma arising from the renal pelvis with immunohistochemical confirmation of the diagnosis. Treatment was extirpative surgery for both primary and metastatic lung lesions as well as adjunctive radiation and chemotherapy. This patient remains disease-free twelve months following treatment. PMID- 1502756 TI - AIDS presenting as primary testicular lymphoma. AB - A case of AIDS presenting as a primary testicular lymphoma is reported. Despite the lack of evident systemic disease, such a presentation in a young patient should alert the physician to the possible presence of an underlying human immunodeficiency virus infection. PMID- 1502758 TI - A modification of extravesical ureteroneocystostomy in kidney transplantation. PMID- 1502759 TI - Clinical value of pathologic changes after intravesical BCG therapy of superficial bladder cancer. AB - Bladder pathologic features related to intravesical bacillus Calmette-Guerin (BCG) therapy in superficial bladder cancer (Ta, T1, Tis) were evaluated and related to clinical outcome. A total of 105 patients were treated with 75 mg Pasteur BCG weekly for six consecutive weeks. When tumor was not demonstrated a maintenance course was given. An additional six-week course was given when tumor recurrence or persistence, without progression, was observed after the induction course. An inflammatory change in the bladder was the most common pathologic finding. Granuloma was the only specific BCG-related feature and did not appear to be a prognostic factor because of low incidence (24%) and lack of correlation with clinical course. Dysplasia occurred more frequently (57%) in nonresponder patients and (26%) in responder patients, often heralding recurrence of tumor. All patients showing concurrent squamous and/or glandular metaplasia were unresponsive to BCG therapy. Histology and cytology did not correlate perfectly: cytology was ineffective in low-grade tumors and improved diagnostic accuracy, particularly when dysplasia was histologically evident. PMID- 1502760 TI - Tumor-associated tissue inflammatory reaction and eosinophilia in primary superficial bladder cancer. AB - In a retrospective study the data of 428 patients with primary superficial transitional cell carcinoma of the bladder were evaluated. The histologic slides were reviewed for presence of a tumor-associated tissue inflammatory reaction, especially tumor-associated eosinophilia. Tumor-associated cell infiltration was found in 23.1 percent and tumor-associated eosinophilia in 2.1 percent. Tumor associated cell infiltration was associated with less recurrences (p = 0.01). Tumor progression rate was not significantly influenced by tumor-associated cell infiltration. Tumor-related death rate was lower in the group with tumor associated cell infiltrate (p = 0.50). Using the Cox regression model carcinoma in situ of the tumor margin, tumor-associated cell infiltrate, and grade of differentiation appeared to be important factors in the prognosis for survival. PMID- 1502761 TI - Aminopenicillins in urology. AB - The use of ampicillin and amoxicillin remains a mainstay of urologic prophylaxis and therapy, however ampicillin's effectiveness against aerobic gram-negative bacilli, especially Escherichia coli has steadily decreased over time due to increasing beta-lactamase-induced resistance. Presently, up to 40-60 percent of E. coli may be ampicillin resistant. Since there have been no major resistance problems with enterococci, ampicillin remains the preferred anti-enterococcal antibiotic in penicillin-tolerant patients. Ampicillin/beta-lactamase inhibitor combinations are preferred when penicillins are used to treat ampicillin resistant aerobic gram-negative bacillary urinary tract infections (UTIs). One response to the problem of resistance has been short-course or single-dose therapy for uncomplicated cystitis in immunocompetent adults, which is less likely to cause side effects, bacterial resistance, or alterations in bowel flora. Another response has been to combine the aminopenicillins with beta lactamase inhibitors such as clavulanate or sulbactam. PMID- 1502762 TI - Sutureless vasovasostomy: new technique using experimental microclip in rat model. AB - Standard microscopic suture vasovasostomy represents a challenge to many urologists. It is technically demanding, and requires two to five hours of operative time. In an attempt to decrease the technical demand and the time requirement, we report the use of a microvascular anastomotic clip and compare this microclip to a standard eight-suture nonstented technique and a six-suture stented technique using a hollow, absorbable 0.5-mm polyglycolic acid stent. The control group with suture required an average of 38.5 minutes per anastomosis for the nonstented group and twenty-two minutes for the stented group. The clip group required 7.6 minutes for the unstented vasovasostomy and 6.5 minutes for the stented vasovasostomy. We obtained a 91 percent patency rate for the stented clip group and 100 percent patency for the unstented clip group. In a rat vasovasostomy, the operative time as well as the inherent technical demand were significantly reduced. PMID- 1502763 TI - Urologists and circumcision of newborns. AB - Although urologists have played a key role in performing clinical studies providing the rationale for newborn circumcision, they have not had primary responsibility for the decision to perform the procedure. Recent confirmatory evidence that newborn circumcision has significant preventive health benefits has called attention to previous urologic articles. This review summarizes the contributions of urologists to the controversy on circumcision of newborns over the past sixty years and emphasizes the importance of clinical objectivity in this field. PMID- 1502764 TI - Megabacteriosis in exhibition budgerigars. AB - Megabacteriosis is a common cause of illness and death in exhibition budgerigars. The clinical signs are variable but include weight loss, difficulty in swallowing, vomiting, diarrhoea and sudden death due to haemorrhage. Significant lesions are confined to the proventriculus which becomes inflamed, dilated and ulcerated, and loses its normal architecture, and to the gizzard in which there are degenerative changes in the koilin layer. PMID- 1502765 TI - Trace mineral levels in the guanaco (Lama guanicoe). PMID- 1502766 TI - Surveillance studies on parasitism in wild boar (Sus scrofa) in Punjab, Pakistan. PMID- 1502767 TI - 'Downer ewes'. PMID- 1502768 TI - Pneumocystis carinii infection in foals in the UK. PMID- 1502769 TI - Welfare of farmed fish. PMID- 1502770 TI - Docking of dogs. PMID- 1502771 TI - A survey of benzimidazole resistant nematodes in sheep in three countries of southern England. AB - Faecal samples were collected from 209 randomly selected sheep farms in southern England, and the nematode eggs extracted were tested by an egg hatch assay and by a larval development test for their resistance to benzimidazoles. Benzimidazole resistance was found on 35 per cent of farms tested in East Sussex, 44 per cent in Oxfordshire and 61 per cent in West Sussex. PMID- 1502772 TI - Ultrasonographic study of early embryonic loss induced by Actinomyces pyogenes in cattle. AB - Four cows were inoculated into the uterus with Actinomyces pyogenes between 30 and 41 days of gestation. Gross morphological changes were monitored by rectal palpation and with a realtime B-mode two-dimensional scanner with a 7.5 MHz transrectal linear transducer, shortly before infection and afterwards at three to 12 hours intervals. Two control groups of cows 27 to 50 days pregnant were used: two cows were inoculated with 6 ml of sterile saline into the uterine lumen and four cows were treated with cloprostenol (prostaglandin F2 alpha analogue). There was a change in the uterine fluid from a black, non-echogenic image before infection to a grey or cloudy echogenic image as early as 21 hours after infection. There was an increase in the thickness of the endometrium of the horns and body of the uterus. The embryonic membranes thickened and separated from the endometrium as early as four hours after infection, followed by cessation of the embryonic heart beat, opening of the cervix and abortion. Abortion was followed by an increase in the amount of echogenic intrauterine fluid leading to an increase in the size of the uterus, and the cervix remained open for at least eight days. The area of the corpus luteum remained greater than 2 cm2 throughout the whole period. Intrauterine inoculation with sterile saline had no effects, but the administration of cloprostenol was followed by the death of the embryo and abortion within 72 hours, and the regression of the corpus luteum from greater than 2 cm2 at treatment to 0.4 cm2, 24 hours after abortion.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1502773 TI - Use of information from pig finishing herds for meat inspection purposes. AB - In a field trial on Integrated Quality Control of finishing pigs we evaluated information written on Quality Information Cards (QUIC) for meat inspection purposes. These cards were sent with 3747 shipments of pigs going from the finishing herd to the slaughterhouse. Pig suppliers answered five questions dealing with health problems and the use of drugs during the finishing period. By comparing QUIC answers to recorded post-mortem abnormalities, we found that the information on the QUIC had some, albeit low, predictive value with respect to the abnormalities 'arthritis', 'condemned liver' and lung lesions. Shipments without a QUIC or with a faulty QUIC were considered 'suspect' because higher levels of abnormalities were found in these shipments. These results indicate the potential use of a QUIC. PMID- 1502774 TI - Preselection of finishing pigs on the farm as an aid for meat inspection. AB - The ability of pig suppliers to separate pigs with abnormalities from pigs without abnormalities at the end of the finishing period was investigated. Nineteen hundred and seventy-eight pigs, delivered by 22 pig suppliers, were involved in the experiment. The pigs were inspected on the farm by the pig supplier and, separately, by a veterinary expert. The animals were sent in 22 deliveries to one slaughterhouse. A veterinary meat inspector carried out the ante- and post-mortem inspections. The results of the inspections were compared. The measure of agreement, Cohen's Kappa (CK), indicated a poor (CK less than 0.40) to fair (0.40 less than CK less than 0.75) agreement among the results of the different inspection procedures, depending on the abnormality under investigation. There was a fair to good agreement for the abnormality 'tail lesion' among all inspections. Some findings of the live animal, such as 'straggler', were associated with a wide range of post-mortem abnormalities. It is concluded that preselection is possible and that the economic and practical feasibility of preselection should be investigated. PMID- 1502775 TI - Pathogenicity of two strains of Newcastle disease virus in the grey-breasted helmet guinea fowl. AB - Thirty-five 6-week-old guinea fowl keets, seronegative for maternal antibodies to Newcastle disease virus, were infected with Herts strain (33/56) and Kumarov strain of Newcastle disease virus intramucularly (IM) or intranasally (IN). Clinical signs were first noticed four days post infection (PI) in the group infected IM but five days PI in the group infected IN with Herts strain of Newcastle disease virus. These clinical signs were similar in both groups and included anorexia, droopiness, huddling together, greenish diarrhoea and marked cachexia. Prominent nervous signs, including spasms of the head and neck, were observed in groups infected with Herts strain. The major gross lesions observed were emaciation with prominent keel bone, empty intestinal tract and distended gall bladder in most keets. The histological lesions were characterised by meningoencephalitis, necrosis and loss of lymphocytes from splenic and lymphoid aggregates. There was muscular degeneration and necrosis in the gizzard and mild pulmonary congestion and oedema in some keets. Neither gross or microscopic lesions were observed in keets that had received the Kumarov strain. PMID- 1502776 TI - Congenital tremor in Holstein Friesian-cattle. AB - In a female family line of Holstein-Friesian cattle a series of trembling calves was born within a period of ten years. All trembling animals were male; female calves appeared normal. At necropsy of one calf severe degenerative lesions of spinal cord and brain white matter were observed. Both myelin and axons were lost and some macrophages occurred within digestion chambers. Obviously degenerated neurones were not found. The lesion was interpreted as a single recessive sex linked hereditary trait. PMID- 1502777 TI - Occurrence of Salmonella in swine in the Latium Region (central Italy) from 1980 to 1989: a retrospective study. AB - An extensive survey was carried out on 849 biological samples (dead animals, organs and viscera, faeces, and rectal swabs) from pigs in the Latium Region (Central Italy) throughout the years 1980-1989. In total, 46 of the samples (5.4%) were found to be bacteriologically positive for salmonellae. Among dead animals, typical gross lesions were observed in 6 clinically infected animals. As far as serotypes are concerned, 11 different ones were isolated, with a predominance of Salmonella typhimurium (26.1%), S. anatum (21.7%), S. bovis morbificans (15.2%), and S. heidelberg (10.8%). According to Kauffmann-White's classification scheme, 39.1% of the isolated strains belonged to serogroup B, 13% to serogroup C1, 17.4% tot serogroup C2, 6.5% to serogroup D, and 23.9% to serogroup E1. In conclusion, the authors speculate that the relatively low Salmonella isolation frequency (5.4%) reported in this study was not dependent upon the cultural procedures used, since different enrichment and plating methods were used, but rather upon the great number of rural-type herds which were investigated over the decade compared to industrial-type herds. Other factors such as stress conditions, which are particularly pronounced in industrial-type herds, and overall climatic situations, which tend to be characterised by warm, dry and long summers in the Latium Region, are also considered in this respect. PMID- 1502778 TI - Towards a sustainable livestock production in developing countries and the importance of animal health strategy therein. AB - Livestock and animal health development projects have not always led to substantial increases in animal productivity or in farmers' welfare. Some have even resulted in unsustainable systems, when they were not based on an understanding of (livestock) production systems. The multipurpose functions of livestock and complex relationships between the biological, technical and social components require a systems approach, whereby nutrition, animal health, breeding, biotechnology knowhow, inputs and technologies are used to optimise resource use. The challenge for developed and developing countries is to reverse the current degradation of the environment, and arrive at sustainable increases in crop and livestock production to secure present and future food supplies. For rural development, governments should show long term commitment and political will to support the rural population in development programmes, because smallholders (including women and landless livestock keepers) represent a large labour force in developing countries. Different systems need different approaches. Pastoral systems must focus on effective management of grazing pressure of the rangelands. Communal rangelands management involves not only the development and application of technologies (e.g. feedlots, vaccination campaigns), but also land tenure policies, institutional development, economic return and a reduction in the number of people depending upon livestock. Smallholder mixed farms must aim at intensification of the total production system, in which external inputs are indispensable, but with the emphasis on optimum input-output relationships by reducing resource losses due to poor management. Resource-poor farming systems must aim at the improved management of the various livestock species in backyards and very small farms, and proper packages for cattle, buffaloes, sheep, goats, rabbits and poultry should be developed. Specialised commercial livestock farming systems (poultry, pigs, dairy or meat) can only be sustainable with adequate marketing, supply of quality feed, veterinary services, labour, management and control of pollution. Animal health programmes play a keyrole in the proposed system approach. PMID- 1502779 TI - Oral administration of calcium chloride-containing products: testing for deleterious side-effects. AB - Two products that contain CaCl2 and that are intended for oral administration were tested for safety aspects. One product contained CaCl2 as a gel, the other contained CaCl2 in an oil emulsion. Oral administration of the CaCl2-containing products caused minor to severe damage to the mucosa of the forestomach and abomasum. The gel solution especially proved to be highly caustic, while the oil emulsion appeared to be relatively safe. PMID- 1502780 TI - Trypanosome infections in warthogs (Phacochoerus aethiopicus) in the Gambia. AB - The prevalence of trypanosome infections in warthogs (Phacochoerus aethiopicus) in The Gambia was found to be 11% of a sample of 62 animals. All isolates were identified as Trypanosoma simiae. Serological evidence indicated a higher level of exposure to T. simiae, but results were inconclusive for the presence of Trypanosoma congolense. The course of T. simiae infection in warthog piglets showed a rapidly rising parasitaemia, with a concomitant fall in packed cell volume, and resulted in a prolonged period of low-level parasitaemia. The same infections killed domestic piglets. PMID- 1502781 TI - Species of coccidia occurring in lambs in Sao Paulo State, Brazil. AB - The purpose of this experiment was to characterize the species of Eimeria affecting lambs and their infection pattern. Faecal samples were collected from each animal at 14-day intervals, beginning when lambs were 2 weeks old and ending when they were 32 weeks old. The oocysts were counted and identified as E. intricata, E. parva, E. pallida, E. crandallis, E. bakuensis, E. weybridgensis, E. ahsata and E. ovinoidalis. The highest oocyst counts were observed when the lambs were 4-8 weeks old. PMID- 1502782 TI - Epidemiologic observations on porcine cysticercosis in a rural community of Michoacan State, Mexico. AB - The prevalence of and risk factors for Taenia solium infection (cysticercosis) in pigs were studied in a rural community in Michoacan State, Mexico. Visual inspection of the tongues of 216 pigs revealed cysticerci in 14 (6.5%). The prevalence was slightly higher in male (10/105) than female pigs (4/110) (P = 0.06) and increased with age (P less than 0.05). The most important risk factors for infection in pigs were access to human feces at a public washing area (P = 0.004), the presence of an indoor latrine (P = 0.05) and indiscriminate disposal of human feces around the pig owner's household (P less than 0.1). Effective and long-lasting control of the transmission of T. solium from humans to pigs must include measures to deny pigs access to human feces, a change which is likely to be resisted because of the traditional and functional aspects of established pig rearing practices. PMID- 1502783 TI - Moxidectin: systemic activity against common cattle grubs (Hypoderma lineatum) (Diptera: Oestridae) and trichostrongyle nematodes in cattle. AB - Moxidectin, a systemic insecticide, was evaluated for its efficacy against the migrating first instars of the common cattle grub, Hypoderma lineatum, and against nematode egg production in beef cattle. It was observed that all three levels (0.1, 0.2 and 0.4 mg moxidectin kg-1) were 100% effective against cattle grubs when administered as a s.c. injection. The same levels of treatment were very effective (90-100%) in reducing trichostrongyle nematode egg production. However, there was a slight indication that at least one species, Cooperia oncophora, was not completely eliminated, as it was observed that small numbers of eggs began to appear after 2 weeks post-treatment when there had been no opportunity for reinfection. PMID- 1502784 TI - Resistance of St. Croix lambs to Haemonchus contortus in experimentally and naturally acquired infections. AB - Parasitological and immunological parameters of experimental or naturally acquired infections with Haemonchus contortus were compared in St. Croix and Dorset lambs. In experimental infections, St. Croix lambs developed significantly greater levels of resistance to H. contortus, following primary exposure, as compared with Dorset lambs. This resistance was influenced both by age and by prior exposure to parasites. In grazing experiments on H. contortus-infected pasture, St. Croix lambs shed significantly fewer eggs as early as 5 weeks following initial exposure. Further, St. Croix lambs had more than 99% fewer worms in the abomasum at necropsy compared with age-matched Dorset lambs. Lymphoproliferative assays using peripheral blood mononuclear cells and antigen specific serological tests demonstrated only minor differences in immune responsiveness between the two breeds despite the dramatic parasitological differences. Similarly, abomasal mucus from both breeds had elevated levels of parasite-specific antibodies and contained substances mediating larval paralysis. In contrast, St. Croix lambs which had become resistant to nematode infection had dramatically higher numbers of globule leukocytes in the abomasal mucosa compared with Dorset lambs. PMID- 1502785 TI - Efficacy of moxidectin against naturally acquired nematode infections in cattle. AB - The efficacy of moxidectin, a new endectocide against natural nematode infections, was evaluated. Twenty-five calves were divided into two groups of eight calves each and a third group of nine calves. Moxidectin was administered s.c. to two groups (I, 0.2 mg kg-1 body weight (BW); II, 0.3 mg kg-1 BW) and the third group (III) received the vehicle (placebo) s.c. Two pre-treatment and one post-treatment faecal nematode egg count determinations were made from all calves, and they were necropsied 2 weeks after treatment for the identification and enumeration of nematode parasites. Group III calves, which received the drug free vehicle, harboured eight species of nematodes (Ostertagia ostertagi, Trichostrongylus axei, Cooperia oncophora, Cooperia punctata, Nematodirus helvetianus, Trichuris discolor, Oesophagostomum radiatum and Dictyocaulus viviparus). The mean total worm burden for this group was 8935. There was a significant reduction in the numbers of many species of nematodes (Ostertagia, Trichostrongylus, Cooperia and Nematodirus) in both treated groups. Cooperia oncophora was reduced by 94% in Group I and by 96% in Group II, while all other nematode species were reduced by 99%. Immature stages of Ostertagia and Nematodirus were significantly reduced in the two treated groups. Two weeks after treatment, the mean faecal egg counts of both treated groups were reduced by more than 98%. There was no significant difference in mean total worm burdens or egg counts between the two treated groups. PMID- 1502786 TI - The efficacy of an albendazole intraruminal controlled-release device against gastrointestinal parasitism in lambs. AB - The effectiveness of albendazole in a controlled-release bolus in controlling gastrointestinal nematodes in lambs was assessed during the summer of 1986. Faecal egg counts were almost entirely negative throughout in the treated group and larval challenge remained low at below 2000 larvae kg-1. Untreated control lambs showed a characteristic pattern of auto-infection, culminating in a peak pasture larval count of over 70,000 larvae kg-1 and an outbreak of parasitic gastroenteritis in September associated with a serum pepsinogen concentration of 1.183 IU tyrosine and a mean worm burden of 91,165 nematodes at necropsy, including Ostertagia, Trichostrongylus and Nematodirus species. Subject to the restrictions imposed by the size of the bolus, this was considered to be a highly effective method of seasonal parasite control. PMID- 1502787 TI - Oral and parenteral administration of ivermectin to reindeer. AB - The anti-parasitic effect of the orally administered paste formulation of ivermectin (Ivomec) in reindeer was evaluated by means of a trial designed to compare the efficacies of orally and s.c. administered ivermectin at the same dosage (0.2 mg kg-1 body weight) in naturally infected adult reindeer (n = 92). Both formulations were 100% effective against larvae of the warble fly, Oedemagena tarandi, while oral treatment was less efficacious than s.c. injection against parasitic nematodes. Both formulations, but particularly the injectable ivermectin treatment, increased the weight gain of pregnant females compared to that of those not treated. PMID- 1502788 TI - Seasonal occurrence of Karoo paralysis in Angora goats in relation to the infestation density of female Ixodes rubicundus. AB - The seasonal occurrence of Karoo paralysis in relation to the infestation density of female Ixodes rubicundus was investigated in an enzootic area of the southwestern Orange Free State, South Africa. Young and adult Angora goats were exposed to infestation during two paralysis tick seasons. Only the young goats became paralysed and their infestation densities (female ticks kg-1 host body weight) were significantly higher than those of healthy animals. The infestation densities on paralysed goats varied between 0.64 and 3.56 ticks kg-1. During the 1988 season, 30% of the naive young goats became paralysed compared with 67% the following season. Twenty-nine percent of previously paralysed goats were paralysed again during the same season. Paralysis occurred during periods of peak tick activity (April-June). PMID- 1502790 TI - Epidemiological observations on Gasterophilus intestinalis and G. nasalis in donkeys from Morocco. AB - During a 24 month period, 198 donkeys were examined for Gasterophilus intestinalis and Gasterophilus nasalis larvae. Gasterophilus intestinalis was found in 97.5% and G. nasalis in 95.5% of donkeys. The third instars (L3) of both species occurred during all months of the year and so did the second instars (L2), except in April (G. nasalis) and May (G. intestinalis). Over 75% of the animals had up to 200 larvae and 1.5% had over 600 larvae. The maximum number of both L2 and L3 larvae found in any animal was 418 G. intestinalis, 433 G. nasalis and 715 of both species combined. The seasonal variation in the numbers and development status of larvae indicated that the period of greatest activity of adult flies of G. intestinalis was from August/September to November, and that of G. nasalis from May to September. Consequently, the L2 larvae in the stomachs were in peak numbers between November and January for G. intestinalis and between July and September for G. nasalis. The L3 larvae of G. intestinalis had peak numbers between December and July, and those of G. nasalis between October and March. During January-March, most of the L2 larvae of G. nasalis were trapped in polypous nodules near the pyloric end of the stomach. It is concluded that the high-risk period for infection is during late spring and autumn, leading to the heavy larval burden of Gasterophilus in the stomach of donkeys during winter. PMID- 1502789 TI - Critical and controlled tests of activity of moxidectin (CL 301,423) against natural infections of internal parasites of equids. AB - The activity of moxidectin was evaluated in 1988 and 1989 against natural infections of internal parasites in 20 critical tests (n = 20 equids) and three controlled tests (n = 20 equids). Two formulations, injectable administered intramuscularly (i.m.) or intraorally (i.o.) and gel i.o., were given at dose rates of 0.2, 0.3 or 0.4 mg kg-1 body weight. For the critical tests (all three dose rates evaluated), removals of second instar Gasterophilus intestinalis were 93-100%, except (89%) for the injectable formulation (i.m.) at 0.2 mg kg-1. Removals of third instar G. intestinalis were 88-100% for the injectable formulation given i.m. or i.o. and 93-100% for the gel formulation, except (53%) for one batch (0.4 mg kg-1). Activity was 100% for third instar Gasterophilus nasalis, Parascaris equorum, Strongylus vulgaris and Strongylus edentatus. For Oxyuris equi, removals were 91-100%, except (27%) for one batch of the injectable formulation given i.o. at 0.3 mg kg-1. There was apparent activity against migrating S. vulgaris and S. edentatus at various dose rates and routes of administration for both formulations. At necropsy, there were local reactions observed at the injection site of three equids. In the controlled tests, dose rates were 0.2 or 0.4 mg kg-1. Removal of third instar G. intestinalis was highest for the injectable formulation given i.m. All formulations and dose rates were highly effective against S. vulgaris and S. edentatus, but variable and incomplete against O. equi. Removal was excellent on Habronema muscae and on migrating S. vulgaris and S. edentatus, although incomplete on S. vulgaris. Gasterophilus nasalis third instars and P. equorum were present in low numbers in some non-treated equids, but none were recovered from treated equids. Toxicosis was not evident. PMID- 1502791 TI - Studies on naturally acquired immunity to African ticks. II. Observations on cattle exposed to Rhipicephalus appendiculatus under varying periods of repeated infestations. AB - Groups of Friesian cattle were infested repeatedly with Rhipicephalus appendiculatus at weekly intervals (eight infestations) and at intervals of 3 weeks (seven infestations) and 6 weeks (seven infestations). The engorgement weight of adults, nymphs and larvae decreased significantly initially, from the second infestation, but rose significantly at later infestations. This rise was more dramatic with larval instars than with any other. A new method for quantifying the resistance status of animals was introduced; this method showed that the resistance acquired by cattle during 6-weekly reinfestations was more stable than that acquired by cattle during weekly and 3-weekly reinfestations. The criteria for assessing natural resistance to ticks was reappraised. These are classified into those serving long- and short-term purposes, and those which have direct and indirect effects. Criteria which could serve long- and short-term purposes include a reduced number of engorged ticks, an increased number of dead male and female ticks, a decreased number of ticks which fed above the critical engorgement weight and an increased number which fed within the pre-mating weight and decreased the number of copulations. The criterion of reduced engorgement weight can serve the short-term purpose only. A new manifestation of resistance to ticks, i.e. decreased moulting weights of nymphs and adults, together with the criterion of decreased egg hatchability, were classified as indirect effects because they were manifested after the ticks had dropped off the resistant cattle. PMID- 1502792 TI - Salivary and serum antibodies in experimental canine taeniasis. AB - Specific IgG and IgA antibodies against adult Taenia pisiformis excretory/secretory antigen were detected in sera and saliva by enzyme-linked immunosorbent assay (ELISA) in experimentally infected dogs. IgG titres in serum and IgA in saliva corresponded with infection status, while serum IgA levels closely reflected faecal egg counts. The salivary IgA response was particularly raised and could have significant immunodiagnostic use for taeniasis in dogs. PMID- 1502793 TI - Efficacy of moxidectin against an ivermectin-resistant strain of Haemonchus contortus in sheep. AB - The efficacy of moxidectin was determined against ivermectin-susceptible and resistant strains of Haemonchus contortus. At the onset of the trial, 40 lambs were each infected with 5000 third stage larvae of one of two strains of Haemonchus contortus. The lambs were randomly sorted into eight treatment groups 28 days post-infection and were treated as follows: Group 1, susceptible strain with no treatment; Group 2, resistant strain with no treatment; Group 3, susceptible strain treated with 0.2 mg moxidectin kg-1 body weight; Group 4, resistant strain treated with 0.2 mg moxidectin kg-1; Group 5, resistant strain treated with 0.4 mg moxidectin kg-1; Group 6, susceptible strain treated with 0.2 mg ivermectin kg-1; Group 7, resistant strain treated with 0.4 mg ivermectin kg 1; Group 8, resistant strain treated with 0.8 mg ivermectin kg-1. The lambs were killed 1 week post-treatment. Comparisons were made among groups based on the number of eggs per gram of feces on the day of treatment and the numbers of worms recovered from each lamb. Both moxidectin and ivermectin were effective in removing susceptible Haemonchus with efficacies of 100% and 99.7%, respectively. The efficacy of moxidectin against the resistant strain was 99.9% and 100% at 0.2 mg kg-1 and 0.4 mg kg-1, respectively, whereas there were only 38.8% and 53.1% efficacies in the lambs treated with 0.4 mg ivermectin kg-1 and 0.8 mg kg-1 body weight, respectively. PMID- 1502795 TI - Optical density spectra of the macular pigment in vivo and in vitro. AB - A precise relative optical density spectrum of the macular pigment, based upon its dichroic properties, was determined. The spectrum proved essentially identical to that of liposome-bound zeaxanthin and lutein, a system duplicating the macular pigment and its environment. Substantial agreement was also found with the spectra of Wyszecki and Stiles (1982, Color science: Concepts and methods, quantitative data and formulae. New York: Wiley) and Vos (1972, Institute for Perception, RVO-TNO, IZF 1972-17, Soesterberg, The Netherlands), and the latter is recommended as a standard. For 7 subjects, the pigment density spectrum derived from foveal and extra-foveal sensitivities was compared with the dichroism-based spectrum. Results indicated that the pigment is described by a common distribution of molecular orientations for all subjects. PMID- 1502794 TI - Resistance to benzimidazole anthelmintics by trichostrongyles in sheep and goats in north-west Cameroon. AB - Following the routine use of tiabendazole at monthly intervals for several years, the trichostrongyle parasites of sheep and goats on a government research station in North-West Cameroon had become resistant to benzimidazole anthelmintics. PMID- 1502796 TI - Evidence for two distinct nonlinear components in the human pattern ERG. AB - We obtained the electroretinogram (PERG) in three observers to a 4.6 c/deg grating pattern with a sinusoidal luminance profile which was modulated in time simultaneously with two sinusoidal temporal frequencies (f1 and f2), or at a single frequency (either f1 or f2). Input temporal frequency ranged from 2.4 to 7.5 Hz. A pattern modulated in the counterphase mode with a single frequency produces a response containing only even harmonics of that frequency. However, when the pattern is counterphase modulated with both f1 and f2, the PERG contains second order response frequencies corresponding to intermodulation components (sums and differences) between the two fundamental frequencies. Such frequencies do not exist in the stimulus--they can only be generated by nonlinear neural interactions. Our results provide evidence for at least two nonsaturating nonlinear response mechanisms in the human retina. PMID- 1502797 TI - Influence of gravitoinertial force level on vestibular and visual velocity storage in yaw and pitch. AB - Velocity storage is an important aspect of sensory-motor control of body orientation. The effective decay rate and three-dimensional organization of velocity storage are dependent upon body orientation relative to gravity and also are influenced by gravitoinertial force (G) level. Several of the inputs to velocity storage including otolithic, somatosensory, proprioceptive, and possibly motor are highly dependent on G level. To see whether the G dependency of velocity storage is related to changes in the effective coupling of individual sensory inputs to the velocity storage mechanism or to alterations in the time constant of velocity storage per se, we have studied horizontal vestibular nystagmus, horizontal optokinetic after nystagmus (OKAN) and vertical vestibular nystagmus as a function of force level. Horizontal OKAN and vestibular nystagmus both showed no effect of G level on their initial or peak slow phase velocities but their decay rates were quicker in 0G and 1.8G than in 1G. Vertical vestibular nystagmus also showed no effect of G level on peak velocity but decayed quicker in 0G relative to 1G. These-findings indicate that the intrinsic decay rate of a common velocity storage mechanism is affected by the magnitude of G. A negligible amount of slow phase eye velocity was observed in planes outside the planes of stimulation, thus short-term changes in G across multiple body axes can change velocity storage, but the change is restricted to the axis common to the rotary stimulus and the G vector. PMID- 1502798 TI - Lower threshold of motion for one and two dimensional patterns in central and peripheral vision. AB - Lower motion thresholds for discriminating opposing motion directions were compared for one dimensional (grating) and two dimensional (plaid) stimuli in central and peripheral vision. The results were consistent with a two-stage model of motion sensitivity in which threshold-limiting noise occurs at both stages, and the speed as well as the direction of the resultant motion is determined by intersection-of-constraints (IOC) from the component motions. The results do not support a purely geometric interpretation of the IOC model, in which thresholds for plaid stimuli are related to thresholds of component gratings by a geometric factor. Neither do the data favour explanations in which local luminance features (i.e. blobs) are detected and their velocity determined. Monte-Carlo simulations of the two-stage process predict thresholds across variations in component direction, contrast, and visual field eccentricity. Lower motion thresholds for gratings and plaids both follow a saturating function of contrast; the fit between grating and plaid data is improved when the plaid contrast is expressed in terms of the contrast of its components. Although less contrast saturation was found in the periphery, in relative terms, plaid and grating motion thresholds were similar in central and peripheral vision, implying cortical magnifications are similar for mechanisms which process grating and plaid motion. PMID- 1502799 TI - Perceived direction of moving two-dimensional patterns depends on duration, contrast and eccentricity. AB - Type II two-dimensional motion is produced by superimposing two one-dimensional drifting cosine gratings with velocity vectors lying on the same side of the intersection-of-constraints (IOC) resultant. When type II patterns were constructed with components having the same spatial frequency and contrast, perceived direction was found to be biased toward the vector sum direction at short durations and approached the direction predicted by IOC only after some time lag. This time lag was contrast dependent. At 5% contrast, the perceived direction after 1 sec of presentation remained biased by more than 20 degrees. Direction perception was also measured at 15 degrees eccentricity. At this eccentricity the perceived direction of type II patterns was grossly biased away from the IOC prediction in the direction of the component vectors by an average of 25 degrees. PMID- 1502800 TI - Properties of cyclopean motion perception. AB - This study investigated the ability of human observers to discriminate the direction of laterally-moving cyclopean stimuli, in order to assess some of the properties of stereoscopic mechanisms that mediate the perception of cyclopean motion (motion existing at levels of binocular integration). The stimuli were moving grating patterns created from dynamic random-dot stereograms. Experiment 1 showed that duration thresholds for discrimination decrease with velocity; they are not governed by temporal frequency nor a constant spatial displacement. Experiment 2 revealed that discrimination thresholds increase with disparity magnitude, for both the crossed and uncrossed disparity directions equally. Experiment 3 showed that the rate of temporal variation at and above which direction discrimination fails (cyclopean upper limit of temporal resolution) is 8 Hz. Our results indicate that a mechanism for motion perception exists at binocular-integration levels of the visual system, which supports a model of motion perception that posits the existence of first-order and second-order processes. PMID- 1502801 TI - Competing motion paths in sequence of random dot patterns. AB - Global motion perception from a sequence of random dot patterns has been studied by means of the competition technique which consists of making a normally less salient motion path in a superimposed multiple-path stimulus more powerful by adding luminous energy to elements forming this path. The perceived motion direction of a sequence of random dot patterns can be dramatically changed by increasing luminance of some fraction of dots leaving all spatial and temporal intervals between dots unchanged. The threshold luminance increment delta I that is required in order to change the perceived motion direction indicates that differently oriented local motion vectors are resolved into a single common motion vector along which the whole pattern appears to move. An inverse spatial proximity rule was discovered: within a certain spatial limit the motion strength of a particular motion path is proportional to the distance between stimulus elements forming this path. PMID- 1502802 TI - Eye movements during motion after-effect. AB - Using the magnetic search coil technique, we measured torsional eye movements in four male subjects during and after rotation of a visual display around the line of sight. During rotation of the display, subjects developed a torsional nystagmus with slow-phases in the direction of target rotation that had a typical gain of less than 0.01. Upon cessation of display motion, subjects experienced a motion after-effect (MAE) in the direction opposite prior target rotation, which persisted for greater than 15 sec. During this MAE, slow-phase eye movements of low velocity were in the same direction as the MAE, but did not persist as long as perceptual effects. In separate experiments, horizontal eye movements were recorded during horizontal stimulus motion; during MAE, no eye movements occurred due to stronger fixation mechanisms. We conclude that MAE is not caused by retinal slip of images, but MAE and the accompanying eye movements might be produced by shared or similar mechanisms. PMID- 1502803 TI - Effects of flicker modulation depth on the detection of changes in target location. AB - Response times to a change in location of a small, low contrast target in a uniform flickering field were investigated under a range of flicker modulation depths. Increasing depth of modulation gave an increased response time for modulation depths from 0% (no flicker, to approx. 35%. Further increases in modulation depth had only a marginal effect on response time. It is shown that this effect is not due to flicker adaptation. The functional form of the modulation dependence is qualitatively similar to that reported by Badcock and Smith (1989, Vision Research, 29, 803-808), but shows a large difference in the modulation at which a levelling of performance occurred. It is shown that this difference is consistent with the presence of a third temporal filter, as proposed by Mandler and Makous (1984, Vision Research, 24, 1881-1887). PMID- 1502804 TI - Wavelength discrimination as a function of field intensity, duration and size. AB - Wavelength discrimination was measured in 8 normal observers as a function of test field intensity (2.5-63 td), duration (0.5-5 sec) and dia (0.5-2 degrees) to determine the conditions under which the just noticeable difference (JND) is smallest. The wavelengths of the standard and comparison hemifields were always equated for the observer's sensation luminance. For field intensity and duration, the wavelength JND was found to decrease until these parameters were increased beyond a certain value--25 td and 1.0 sec, respectively--and to remain constant thereafter. For field diameter, however, the JND was smallest only within a very limited range of values--between 1.0 and 1.5 degrees--and increased sharply with smaller and larger values. PMID- 1502805 TI - Binocularity of early motion mechanisms: comments on Georgeson and Shackleton. AB - The demonstration of compelling dichoptic illusions of motion using a variety of stimuli, all of which share the property that left and right eye patterns were spatio-temporal quadrature pairs, has been interpreted as evidence for binocular integration in the early motion system (short range motion). Georgeson and Shackleton (1989, Vision Research, 29, 1511-1523) have recently challenged this position based on results using 3 types of stimuli, sinusoidal gratings, random line kinematograms and missing fundamental squarewaves. For each class of stimuli motion was perceived during dichoptic presentation, but certain limitations led them to conclude that early motion mechanisms are defeated when no motion is present monocularly. We do not dispute their data, rather an alternative interpretation is offered which supports the position that early motion sensors are capable of binocular integration, a property well established physiologically. PMID- 1502806 TI - Cones in the retina of the Mongolian gerbil, Meriones unguiculatus: an immunocytochemical and electrophysiological study. AB - Immunocytochemistry revealed in the retina of the Mongolian gerbil three immunologically distinct photoreceptor cell types. Rods comprising about 87% of the total receptor population were selectively recognized by an antirhodopsin serum (AO). The most abundant cone type (11-13% of photoreceptors) was labeled by the monoclonal antibody COS-1, specific in mammals to the middle-to-long-wave sensitive cone visual pigments. A minor cone population (2.5-5% of the cones) reacted with the monoclonal antibody OS-2, shown earlier to bind to the blue cones in mammalian species. Color substitution experiments revealed on the ERG level a color discrimination capability which must be attributed to the cooperative activity of green-sensitive (COS-1 positive) and blue-sensitive (OS-2 positive) cones. We conclude that the Mongolian gerbil has a well developed cone system, and that it may possess dichromatic green-blue color vision. PMID- 1502807 TI - No evidence for dichoptic motion sensing: a reply to Carney and Shadlen. AB - Georgeson and Shackleton (1989, Vision Research, 29, 1511-1523) confirmed the existence of dichoptic apparent motion (AM), but argued that its basis was the spatio-temporal correspondence of visible features ("feature tracking"), not early motion sensors. Direction selectivity in motion sensors was probably purely monocular. The key evidence came from AM of missing-fundamental (MF) gratings. Monocular MF motion was always reversed, implying motion sensors responding to the third harmonic (3f) component. Dichoptic MF motion was in the correct direction at the higher contrasts and lower drift rates, and overall was highly correlated with judgements of pattern structure, suggesting feature-tracking. Carney and Shadlen (1992, Vision Research, 32, 187-191) criticized some of our methodology and the theoretical interpretation. Their central argument was that dichoptic AM for sine-waves did reflect dichoptic motion sensing, but was less reliable at higher contrasts. Hence forward motion of the dichoptic MF pattern should occur only where sine-wave (3f) motion-sensing declines. We discuss their critique, and find little support for it. We also present additional data on dichoptic AM for 3f and 5f gratings, showing that Carney and Shadlen's predictions were not upheld. Feature tracking remains the most plausible account of dichoptic AM. PMID- 1502808 TI - On the square root intensity coding at the level of cone photoreceptors. AB - In psychophysics as well as in sensory physiology, the response amplitude R is often a power function of the stimulus intensity S over a wide range of S (i.e. R = aSk; a = constant). In vision, there is a recent report that such a power relationship ("square root intensity coding" if k = 0.5) may arise as early as at the cone photoreceptor level if the stimulus is a narrow slit of light. A simple model is presented here to account for this finding: strong electrical coupling with several neighboring cones can act to expand the dynamic range of the impaled cone in such a way as to produce a square root coding region for the responses to fine visual objects such as small spots and narrow slits. PMID- 1502809 TI - Magnetic resonance microscopy of rabbit eyes. AB - Magnetic resonance (MR) micro-imaging was performed on enucleated eyes from rabbits previously injected with perfluoropropane gas (C3F8), with or without the surgical creation of retinal detachment. Condensed vitreous, which exhibited shortened longitudinal relaxation time (T1), could be differentiated with proton density and T1-weighted imaging. Gradient-echo imaging could in addition detect vitreo-retinal tractions. The detached retina itself was also seen. Further, proton-density but not T1-weighted imaging showed lens opacities appearing as high-intensity regions. MR microscopy is a convenient method for gross morphological examination of intact eyes. PMID- 1502810 TI - Experimental evidence that rearing kittens in stroboscopic light retards maturation of the visual cortex: a new tool for studying critical periods. PMID- 1502811 TI - Temporal properties of human visual filters: number, shapes and spatial covariation. AB - The temporal properties of the foveal visual filters were revealed using a method which is a variant on previously used noise masking paradigms. This enables the temporal properties of the mechanisms underlying threshold detection of a spatio temporal probe to be measured. In accord with recent suggestions these results support the existence of three temporal mechanisms. The evidence for the third, higher temporal mechanism is only persuasive at low spatial frequencies. Furthermore, the results suggest that although there is some degree of spatio temporal covariation in the filtering properties either of individual filters or across the filter population, the well known spatio-temporal covariation in human detection sensitivity is adequately explained by a sensitivity scaling of individual temporal filters with approximately invariant temporal properties. PMID- 1502812 TI - Temporal frequency filters in the human peripheral visual field. AB - The temporal filtering properties of the human peripheral field were investigated by means of measuring: (1) modulation transfer functions for a range of spatial frequencies at four visual field locations (0, 10, 30 and 50 degrees), (2) the contrast of a masking stimulus required to extinguish the visibility of just suprathreshold probes. Results suggest that the number of temporal filters governing detection threshold is dependent upon both eccentricity and spatial frequency. For near-foveal viewing three temporal filters were found (one low pass and two band-pass), whereas at far eccentricities only one was found (band pass). A similar result was obtained by modeling the modulation transfer function by simply scaling the sensitivities of three independently derived filters. Our data suggest that (1) changes in the modulation transfer function with respect to spatial frequency and eccentricity can be adequately explained by the changes in sensitivity of a small number of spatio-temporal separable filters; (2) the peripheral field is not merely a coarser version of the fovea but has qualitative differences which may be thought to emphasize the transient properties of the stimulus. PMID- 1502813 TI - Misdirected visual motion in the peripheral visual field. AB - An object moving against a textured background is accurately perceived when viewed foveally, but when viewed peripherally the object's perceived direction of motion may deviate from veridical by as much as 90 deg. The illusory direction is oblique to the orientation of the background contours, which may themselves be moving or stationary. In several experiments, we examined the boundary conditions for occurrence of the illusion and tested hypotheses concerning its basis. This illusion of perceived direction dramatizes differences in motion processing between the fovea and the periphery. PMID- 1502814 TI - Human sensitivity to expanding and rotating motion: effects of complementary masking and directional structure. AB - A comparison of sensitivity to expanding, rotating, translating and random motion suggests the existence of specialised mechanism for the detection of expansion and rotation. Complementary masking shows that the detection of expansion is unaffected by the presence of rotation, and vice versa. These results are interpreted in terms of a Relative Motion System, which combines the outputs of localised motion detectors in a variety of ways, and which functions to analyse complex image motion into simpler, more useful, components. PMID- 1502815 TI - The relationship between vestibulo-ocular reflex plasticity and changes in apparent concomitant motion. AB - The vestibulo-ocular reflex (VOR) and the apparent motion of a spot stimulus fixated during head movement (apparent concomitant motion, ACM) were measured before and after an adaptation period during which subjects attempted fixation of a stimulus which moved either in the same or opposite direction as head oscillations. Movements of the head were voluntary and paced by a metronome at either 0.5 or 2.0 Hz during the 4 min adaptation period. Pre- and post-adaptation measures of VOR and ACM were obtained for both frequencies of head oscillation. VOR and ACM were altered similarly by the period of exposure to correlated head and stimulus motion. Viewing a stimulus moving in the same direction as head motion resulted in decreased VOR gain and increased ACM in the opposite direction as head motion. Viewing a stimulus moving opposite head motion resulted in increased VOR gain and increased ACM in the same direction as head movement. Differences between pre- and post-measures tended to be maximal at the adaptation frequency, but transferred to a lesser degree to the other frequency. The results indicate that changes in motor and perceptual systems are related, and are consistent with the proposal that VOR gain is a determinant of ACM. PMID- 1502816 TI - Directional acuity for drifting plaids. AB - Orientation discrimination thresholds were estimated for symmetrical "plaids", constructed by the super-imposition of two, independent drifting sine-wave gratings of 2.5 c/deg. Experiments were conducted when the apparent direction of drift was on the two principal meridians (vertical and horizontal), and when the apparent direction of drift was at the two oblique orientations (45 and 135 deg). Acuity for the direction of drift for these stimuli is of the same order of precision as orientation acuity for static or drifting gratings, and exhibits a meridional anisotropy that favours the principal meridians. This anisotropy follows a pattern that is determined by the apparent direction of drift, and not the orientation of the underlying elements. Acuity for orientation is lowest for oblique drift directions, even though both of the elements are oriented on the principal meridians. This finding was confirmed when the orientation of the underlying elements was subject to a random variation. The results are not easily accommodated by models that propose that the individual elements of the plaid are analysed separately. Second, the data are incompatible with models of the oblique effect of orientation discrimination that are based on an axis dependent, differential sampling of the retinal image. PMID- 1502817 TI - The Longitudinal Study of Aging: 1984-90. PMID- 1502818 TI - [A new virus of rabbit. II. Study on morphological structure and some physicochemical properties of a strain of rabbit hemorrhagic disease virus]. AB - In this paper a strain of Rabbit Hemorrhagic Disease Virus (RHDV) was isolated and purified from the diseased rabbit livers with a method of using chloroform, two-phase of polyethylene-glycol-dextran sulfate sodium and sucrose density gradient centrifugation. Purified virus was nonenveloped, icosahedeal symmetry with a triangulation number of 3, and 33-37 nm in diameter. The capsid was composed of 32 capsomeres with central holes in an outer diameter of about 9nm. Two types of viral particles having different sedimentation coefficient, 130s and 166s could be identified after sucrose density gradient centrifugation. Probably no less than four virion proteins with molecular weight of 66.4, 65.0, 63.5, 41.0 x 10(3) dalton were detected by SDS-polyacrylamide gel electrophoresis. Viral nucleic acid was extracted from purified virus by using SDS-proteinase K-phenol. Tests with diphenylamine, formaldehyde, and staining with acridine orange as well as the curves of thermal denaturation showed that this kind of virus had a single stranded DNA. The molecular weight of the ssDNA was approx 2.1 x 10(6) dalton as determined by electron microscopy. Data indicate that the RHDV may like the parvovirus of the family Parvoviridae. PMID- 1502819 TI - [Results of multicenter evaluation of reagents for determination of sodium, potassium and chloride ions using enzyme activation]. AB - We present the results of a multicentre evaluation with Boehringer Mannheim/Hitachi instruments of new "enzymatic" methods for the determination of Na+, K+, and Cl- in serum or plasma. The between-day coefficient of variation was less than 1.4% (Na+), less than 2.6% (K+) and less than 1.7% (Cl-). The linear range of the assays were at least 80 to 200 mmol/l (Na+), 1.5 to 17 mmol/l (K+) and about 30 to at least 200 mmol/l (Cl-). The comparisons with routine flame atomic emission spectrometry and coulometry showed a satisfactory agreement of the test results. The "enzymatic" assays are insensitive to even grossly elevated levels of bilirubin and lipids (sodium, potassium, and chloride assays), NH4+ (potassium assay) and amylase (chloride assay). Interference by various drugs was not detected. Since the new methods can easily be adapted to photometric clinical chemistry instruments, they represent a valuable alternative to the use of ion selective electrodes, flame atomic emission spectrometry and coulometry. PMID- 1502820 TI - [Extreme results in electrolyte determination]. AB - Besides statistical quality control, quality control based on patient specimens is an important tool for quality enhancement and thus for an increased diagnostic certainty in laboratory medicine. One of three possibilities of plausibility judgement is the control of extreme results, that is alert and absurd value check. The aim of our study was to look for extremely high or low findings of the most frequently examined clinical-chemical parameters, to scrutinize their validity according to clearly defined criteria and to find out the underlying actual clinical situations and diseases. In this publication only the results for the electrolytes are discussed. Retrospectively the most extreme values of all results for serum sodium, potassium and chloride concentrations of a 21-month interval were extracted in a large university hospital. The clinical situation was then evaluated by reading the medical reports of these patients. The validity of the findings was judged by previously defined criteria and rated as confirmed, questionable and not confirmed. In all cases the survival time was determined. The most extreme confirmed results were for sodium 191 and 100 mmol/l, for potassium 9.0 and 1.3 mmol/l and for chloride 138 and 65 mmol/l. All these findings were compatible with life, at least for several hours. Even if it is probably impossible to give generally valid extreme ranges. Nevertheless our results should certainly have practical importance in absurd and alert value check. PMID- 1502821 TI - [Organization of the laboratory and practicability of methods for electrolyte determination]. AB - Requirements, possibilities, and pitfalls of electrolyte (sodium, potassium, and chloride) analysis are reviewed within the light of the experiences in the Academic Hospital St. Radboud, Nijmegen, The Netherlands. In view of the ever increasing demands on short turnaround times, attention is paid to problems with specimen delivery, instrumentation and data distribution. The precision levels of available alternatives for electrolyte analysis namely: flame photometry, direct and indirect ion selective electrode methods, dry chemistry, and the newly developed enzymatic approach for sodium and potassium analysis are discussed. PMID- 1502822 TI - [Observations on the cost effectiveness of various methods of electrolyte determination]. AB - New analytical methods have to be considered also with respect to their economic efficiency. Here we present the application of an economic analysis based on the rules of applied economics in our institute for clinical chemistry and laboratory medicine. We started with an analysis of laboratory structure and economic efficiency in 1988, which since then has been followed by a continuously performed laboratory controlling system. The results of unit costing show the different cost groups, which add up to the cost of a single electrolyte determination. Regarding the transferability of our data to other laboratories, one has to consider that the main cost groups besides personnel cost are the apportionment of the overhead cost and the depreciation cost; both may vary markedly between each laboratory. Variable cost (reagents and consumables) differ widely from flame photometry to enzymatic electrolyte determination, but they amount only to 3-15% of the total cost. PMID- 1502823 TI - [Determination of electrolytes in serum and plasma]. AB - In clinical chemistry two different quantities are determined for electrolytes: 1) Electrolyte concentration (total) in serum (S) e.g. S-sodium (mmol/l), S calcium (mmol/l). 2) Electrolyte concentration (ionized) in serum water [S(W)] e.g. S(W)-sodium, ionized (mmol/kg), S(W)-calcium, ionized (mmol/kg) ad 1) For the determination of the electrolyte concentration in serum, various methods are used: Sodium, potassium: Flame atomic emission spectrometry, ion-selective electrodes after dilution of the sample, enzymatic methods; Chloride: Coulometry, absorption spectrometry after chemical reaction, enzymatic method; Calcium, magnesium: Flame atomic absorption spectrometry, flame atomic emission spectrometry (calcium), absorption spectrometry after chemical reaction, enzymatic method (magnesium). A safe and unambiguous medical interpretation of sodium and chloride ion concentration in serum is not possible without knowledge of the water concentration or of the lipid and protein concentration of the individual sample. The same holds true--even though for some other reasons--for calcium concentration in whole serum. The reference intervals of the pertinent ions are valid only for samples, which are "normal" with respect to the size of the electrolyte-free compartment and--depending on the method--the amount of complex-binding ions. ad 2) For the determination of the concentration of the "ionized" or "free" fraction of sodium, potassium, calcium, and magnesium in serum water (or the extracellular water phase of whole blood) the following method is only applicable: Ion selective electrode without dilution of the sample. A save medical interpretation of the ionized electrolyte concentration in serum water is possible without knowledge of the water concentration of the individual sample, because these quantities are independent from the size of the electrolyte-free compartment.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1502824 TI - [Enzyme spectrophotometry determination of sodium, potassium and chloride ions in serum and urine]. AB - The principles and main features of enzymatic methods for the measurement of sodium, potassium, and chloride are reviewed and their performance compared with current procedures. Each method makes use of a relatively specific enzyme, catalysing a reaction whose rate is sensitive to the ion to be determined. Where the (S)0.5 of the enzyme for the ion is much lower than the assay concentration, the ion concentration may be reduced by a binding agent. Alternatively, a competitive inhibitor may be used to raise the (S)0.5 of the enzyme. In the case of chloride determination with amylase the (S)0.5 of the enzyme is raised by limiting the concentration of free calcium. In the measurement of potassium, interfering ions such as sodium are removed by binding with Kryptofix 221 and improvement in performance is also achieved by use of a bacterial pyruvate kinase less sensitive to sodium. The enzymatic methods are applicable to measurement of sodium, potassium and chloride in blood or urine with good precision, accuracy, and specificity. They can be used on mechanized or manual instruments. There appears to be minimal interferences from compounds found in normal or pathological serum or urine. PMID- 1502825 TI - An overview of syphilis tests in Korea. PMID- 1502826 TI - Effects of vanadate on vascular contractility and membrane potential in the rabbit aorta. AB - Isolated rabbit aortic ring with intact endothelial cell preparations precontracted with NE (10(-7) M) were relaxed by vanadate in a dose dependent manner (from 0.2 to 2 mM). Application of vanadate and ACh during the tonic phase of high K+(100 mM)-induced contraction showed a slight relaxation in contrast to that in NE-induced contraction, but sodium nitroprusside (10 microM) more effectively relaxed the aortic ring preparations in high K+ contraction than that of vanadate. Vanadate-induced relaxation in NE-contracted aortic rings was reversed by application of BaCl2 (50 microM) or glibenclamide (10 microM). Furthermore, Vanadate hyperpolarized membrane potential of smooth muscle cells in endothelium-intact aortic strips and this effect was abolished by application of glibenclamide. The above results suggest that vanadate release EDHF (Endothelium Derived Hyperpolarizing Factor), in addition to EDRF (Endothelium-Derived Relaxing Factor) from endothelial cell. This EDHF hyperpolarize the smooth muscle cell membrane potential via opening of the ATP-sensitive K+ channel and close a voltage dependent Ca++ channel. So it is suggested that the vanadate-induced relaxation of rabbit thoracic aortic rings may be due to the combined effects of EDRF and EDHF. PMID- 1502828 TI - Subacute necrotizing lymphadenitis--a collective clinicopathological and immunohistochemical study. AB - Subacute necrotizing lymphadenitis (SNL) is a well documented and unique clinicopathologic entity, although its etiology and pathogenesis have not been clearly established. Microscopically, cortical and paracortical necrotizing lesions with karyorrhexis, abundant nuclear debris and infiltration of large mononuclear cells are characteristic. This study analyzed the common clinical and pathological features of 118 patients with SNL and the nature of the mononuclear cells. Patients were generally young women and revealed cervical lymphadenopathy with tenderness, fever, leukopenia and elevation of the erythrocyte sedimentation rate. Features of the adjacent uninvolved area in the lymph node included a starry sky pattern, follicle centers, sinus histiocytosis or aggregation of foamy histicoytes. There was an inverse relationship between the extent of necrosis and of histocytic infiltration but not between the extent of necrosis and the duration from the onset of symptoms to the diagnosis. Immunohistochemically the infiltrated mononuclear cells of the affected foci were T lymphocytes and histiocytes. The clinical, histological and immunohistochemical features suggest that SNL represents a hypersensitivity reaction to certain infectious agent without forming granuloma. PMID- 1502827 TI - Comparative analysis of lipopolysaccharide and lipid antigens of Leptospira interrogans serovars. AB - Lipopolysaccharide (LPS) or glycolipid antigens of Leptospira interrogans have been candidates as serogroup or serotype specific antigen. In this study, therefore, we prepared the LPS and lipid antigens from L. interrogans serovars lai, icterohaemorrhagiae, copenhageni, canicola, pomona, grippotyphosa, and a Korean isolate 30R. The LPS antigens were analyzed by a polyacrylamide gel electrophoresis and lipid antigens by thin-layer chromatography, respectively. The seroreactivity of the antigens were also examined with homologous or heterologous antisera using an enzyme-linked immunosorbent assay. The LPS antigens from serovar lai and the strain 30R were closely related but different from serovar icterohaemorrhagiae. Particularly, the LPS antigens from serovars icterohaemorrhagiae and grippotyphosa were reactive only with the homologous antisera, thus indicating serovar specificity. However, the LPS antigens of the other serovars were reactive to the heterologous antisera. The lipid antigen of serovar icterohaemorrhagiae reacted only with the homologous antisera. In contrast, lipids of other serovars reacted broadly with heterologous antisera, particularly among serovars lai, copenhageni, canicola, pomona, and the strain 30R. The results thus indicated that the LPS and lipid antigens of L. interrogans may contain serovar-specific as well as cross-reactive epitopes. PMID- 1502829 TI - Natural killer activity and antibody-dependent cellular cytotoxicity in patients with primary lung cancer. AB - The NK activity and ADCC of peripheral blood mononuclear cell were examined to evaluate the contribution of ADCC and NK activity to host immune response against lung cancer. The NK activity and ADCC were examined in 58 patients with primary lung cancer and 40 healthy volunteers as normal controls. The NK activity of patients with lung cancer was significantly subnormal, but ADCC was at a normal level. The NK activity was decreased in non-small cell lung cancer (NSCLC), but not in small cell lung cancer (SCLC) compared to normal controls. According to stage, the NK activity in stage II, III-M0 and III-M1 NSCLC showed low levels compared to that of stage I NSCLC, but there was no difference of NK activity in patients with SCLC. The NK activity was not affected by performance status. There was no significant difference of ADCC in patients with lung cancer according to cell type, stage and performance compared with that of normal controls. The NK activity and ADCC were not changed after chemotherapy and operation respectively. PMID- 1502830 TI - Comparison of outcome among double, bifoil and Inoue balloon techniques for percutaneous mitral valvuloplasty in mitral stenosis. AB - The efficacy and complications of three different methods of percutaneous mitral valvuloplasty (PMV) were evaluated in 245 patients with mitral stenosis (MS). Eight six patients (35%) had severe MS defined in the mitral valve area (MVA) less than 1.0 cm2 (0.8 +/- 0.2) and Echoscore greater than or equal to 8(8.9 +/- 1.1). The results including post MCA greater than or equal to 1.5cm2 and complications, i.e, increment of mitral regurgitation (MR) greater than or equal to +1 and atrial septal defect (ASD) with Qp/Qs greater than or equal to 1.5 were compared in overall and in severe MS groups. There was no statistically significant difference in size of MVA before and after PMV between overall patients group and severe mitral stenosis group (0.8 +/- 0.1 vs 1.7 +/- 0.4cm2 in the double technique, 0.8 +/- 0.2 vs 1.5 +/- 0.3cm2 in the Bifoil technique and 0.7 +/- 0.2 vs 1.8 +/- 0.3cm2 in the Inoue technique. p: NS). However, a significantly larger number of patients in the severe MS group had better MVA with the double than the Bifoil technique [MVA greater than or equal to 1.5cm2; 42 (72%) vs 6 (46%), p less than 0.005] whereas higher complications were observed with the Bifoil than the Inoue technique (MR greater than or equal to +1; 9 (69%) vs 4 (27%), ASD (Qp/Qs greater than or equal to 1.5' 6 (46%) vs 2 (13%) p less than 0.005).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1502831 TI - Effect of porcine bone morphogenetic protein on healing of bone defect in the rabbit radius. AB - Segmental long bone defects due to infection or trauma is a difficult problem to manage in patients. We studied the effect of porcine bone morphogenetic protein (pBMP) on healing of defects in the rabbit radius. Porcine BMP was separated and purified from the tibia and femur of pigs by repeated solubilization and precipitation of the protein with different concentrations of urea and GuHCl. The osteoinductive activity of pBMP was confirmed by bioassay using No. 615 mice. In rabbits, about a 15 mm length of radii were removed and 20 mg of pBMP was implanted in the defected area with fibrin sealant (FS), while only FS was implanted in controls. Union of the affected area was observed in 6 weeks in the experimental side. There was no definite evidence of bone bridging across the affected area in the controls. This suggests that pBMP has a bone forming activity in other species and the clinical use of pBMP in treating patients with segmental bone defects is promising. PMID- 1502832 TI - Development of the mucociliary system in the eustachian tube and middle ear: murine model. AB - In order to describe the developmental anatomy of the murine eustachian tube and its related structures, seventy six mice of ages ranging from gestational day 11 to postnatal day 21 were investigated through the light and electron microscopic observations. Development of the ciliated cells was seen concurrently in both the eustachian tube and middle ear on the 16 th gestation day, one day earlier than the epithelial secretory cells appeared in both the eustachian tube and middle ear. The number of ciliated cells and secretory cells increased rapidly after birth. Tubal glands were well identified with evidence of secretory activity around the time of birth. Thus, the findings of this study indicate that the mucociliary defense system starts to develop during the fetal stage and is well established immediately after birth. PMID- 1502833 TI - The development of a decision support system for diagnosing nasal allergy. AB - This paper deals with the problem of improving the capability of the medical decision support system (MDSS) for diagnosing nasal allergy by integrating the previously developed expert system with the neural network approach. Three knowledge acquisition methods were used to develop the expert system: statistical, rule-based, and the combined approach. Among the three, a combined approach showed the best prediction rate based on discriminant analysis. Using the results of a combined approach as input values, the neural network was developed using back-propagation method. Unlike the expert system, the neural network system provides the resulting allergy status in probabilistic terms. Managerial as well as legal issues were also discussed in this paper. PMID- 1502834 TI - Pyogenic arthritis of the hip due to Campylobacter fetus--a case report. AB - Septic arthritis of the hip caused by Campylobacter fetus subsp. fetusis very rare. The authoris isolated C. fetus subsp. fetus from a specimen of the left hip. The patient was a 53-year old man with a history of heavy drinking, diabetes, and chronic hepatitis, and had been suffering from avascular necrosis of both femoral heads. It was considered that the organism invaded already damaged tissue of the joint. The patient was treated with intravenous antibiotics and later received successful total hip replacement. PMID- 1502835 TI - Adjuvanticity and ISCOM formation by structurally diverse saponins. AB - Adjuvant activity and immunostimulating complex (ISCOM) formation by a series of saponins and glycoalkaloids differing in the structures of their aglycones and sugar chains were examined. The only two saponins apart from Quillaia that were adjuvant-active were Gypsophila and Saponaria, which resemble Quillaia in that they contain saponins with branched sugar chains attached to positions 3 and 28 of the aglycone. Glycoalkaloids with a branched sugar chain lacked adjuvant activity. Saponaria saponins formed irregular ISCOM-like structures, and Gypsophila produced a sheet of joined pore-like structures. The alfalfa hederagenin saponin and Quinoa also formed pore-sheets, despite lacking adjuvanticity. PMID- 1502836 TI - Crossed immunoelectrophoretic analysis of antigenic composition of B subunit/whole-cell and whole-cell only killed oral cholera vaccines. AB - Crossed immunoelectrophoresis was used to identify antigens preserved in the whole-cell component of oral cholera vaccines tested in the field trial in Bangladesh. The composition and immunogenicity of the vaccine antigens were compared with those of antigens obtained from live cells of Vibrio cholerae 01 of both biovars and serovars. The whole-cell component of the vaccine contained ten antigens in comparison with the live Vibrio cells which revealed the presence of 30 antigens. The whole-cell component contained lipopolysaccharide, flagellar antigen, one cell-bound haemagglutinin and at least six outer membrane protein antigens. PMID- 1502837 TI - Influenza vaccine strain selection: equivalence of two antigenically distinct haemagglutinin variants of 1989 H3N2 influenza A virus in protection of mice. AB - Precise antigenic analysis with haemagglutinin-inhibition (HI) tests of 1989 H3N2 influenza A viruses with polyclonal ferret, rabbit and mouse antisera has shown, first, significant differences among 1989 wild-type isolates, second, antigenic differences between two high-yield vaccine candidate reassortant viruses, third, significant antigenic differences of one reassortant (X-105) from the wild-type virus (A/Guangdong A/39) from which it was derived, and fourth, dependence of antigenic characterization of viruses upon the host species used in immunization. Nevertheless, the two reassortant viruses (only 43% similar by HI test) were equally protective in preventing homovariant or heterovariant infection in either previously unimmunized or infection-primed mice. These results not only confirm the known antigenic heterogeneity of influenza A viruses, but raise questions about the adequacy of current methods of antigenic characterization of influenza viruses and the basis for decisions on vaccine strain selection. PMID- 1502838 TI - A purified stage-specific 31 kDa antigen as a potential protective antigen against Ostertagia circumcincta infection in lambs. AB - The 31 kDa antigen of third-stage (L3) Ostertagia circumcincta larvae was evaluated as a potential prophylactic antigen by an analysis of the protective, humoral and cell-mediated responses of lambs immunized with this antigen. Six lambs were immunized by subcutaneous injection with a total of 400 micrograms of the purified 31 kDa antigen in 250 micrograms ml-1 Quil A adjuvant. Five sheep given identical injections but without the 31 kDa antigen were used as controls. All animals were challenged with 4.2 x 10(4) infective L3 O. circumcincta larvae 1 week after the last booster injection. The protection afforded by the 31 kDa antigen was demonstrated by a significant reduction in faecal egg counts (p less than 0.05) and total worm counts (p less than 0.005) in vaccinated animals. Elevated ELISA antibody levels specific to the 31 kDa antigen were detected in the sera of vaccinated animals as early as 3 weeks after immunization. Specific antibodies were further demonstrated by Western blot 4 days after the first booster immunization at 3 weeks. In control animals no antibodies to the 31 kDa antigen were detected in Western blots throughout the course of the experiment. Immunized lambs had significantly higher in vitro lymphocyte stimulation indices (p less than 0.05) than control animals. In haematoxylin and eosin stained sections taken at necropsy from vaccinated sheep, compared with control lambs, there were more larvae present in the crypts of the abomasal epithelium and these larvae were surrounded by lymphocytes and eosinophils. In vaccinated lambs a marked infiltration of lymphocytes in the lamina propria and oedema in the submucosa were also observed.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1502839 TI - Reactogenicity and immunogenicity of a double-strength acellular pertussis vaccine. AB - The reactogenicity and immunogenicity of a double-strength acellular pertussis vaccine were evaluated after administration to 16 4-6-year-old children. The vaccine contained toxoided lymphocytosis-promoting factor (6.0 micrograms/dose), filamentous haemagglutinin (70 micrograms/dose), agglutinogens (1.4 micrograms/dose) and the 69 kDa protein (approximately 8.0 micrograms/dose). The vaccine was extremely well tolerated with few minor side effects following immunization. Significant increases in antibodies to all pertussis vaccine components were noted. In summary, this double-strength acellular pertussis vaccine, containing a very high dose of filamentous haemagglutinin, had minimal reactogenicity and was immunogenic. These findings, as well as other studies with this vaccine, indicate that filamentous haemagglutinin is not a major determinant of vaccine reactogenicity. PMID- 1502840 TI - Enhancement of antibody response of turkeys to trivalent avian influenza vaccine by positively charged liposomal avridine adjuvant. AB - Trivalent avian influenza (AIV) antigens (H4N8, H5N2 and H7N3), mixed with positively charged, negatively charged and neutral avridine-containing liposomes, and oil-emulsion were subcutaneously administered to 6-week-old turkeys. Charged liposomal avridine adjuvant, either positive or negative, produced a better antibody response than uncharged liposomal avridine or oil-emulsion adjuvants when used in a trivalent avian influenza vaccine. The antibody response to the different antigens was generally greater to the positively charged adjuvanted vaccine compared with the negatively or neutral charged or oil-emulsion adjuvanted vaccines and these differences were significant (P less than 0.05) with the three antigens. The results suggest that the positively charged liposomal avridine plays a significant role as adjuvant to the AIV antigens. PMID- 1502841 TI - Immunity to Haemophilus influenzae type b on sample population from central Italy. AB - A study on natural immunity to Haemophilus influenzae type b (Hib) was carried out in the province of Siena on 474 subjects ranging in age from 3 days to 70 years. The titration of antibody to capsular polysaccharide (PRP) was performed by the radioantigen-binding assay (RABA) method. A total of 66.67% of the population studied presented an antibody level considered to be protective (greater than or equal to 0.15 microgram ml-1). Seropositivity was 5.7% in the 5 7 month age group and 29.09% in the 8-17 month age group. This rose progressively in successive age groups reaching 79.54% between 4 and 6 years old and a value greater than 90% after 7 years old. From 3 to 17 months even the geometric mean of antibodies to PRP was below the protective limit. Our data indicate that, even in Italy, the majority of the infant population is not protected against H. influenzae, and therefore that vaccination should also be introduced in this country. PMID- 1502842 TI - Immune response to inactivated influenza virus vaccine: antibody reactivity with epidemic influenza B viruses of two highly distinct evolutionary lineages. AB - Vaccination of adults (healthy female employees potentially capable of transmitting influenza to high-risk persons; n = 104) in autumn 1990 with a trivalent influenza virus vaccine containing B/Yamagata/16/88 induced a low antibody response to B/Finland/150/90, a recent variant of B/Victoria/2/87-like viruses, as compared with the antibody response to B/Finland/172/91, a current variant in the lineage of B/Yamagata/16/88-like viruses. Up to the end of the epidemic season, the antibody status declined but was still significantly better than before the vaccination. The results suggest that the vaccine strain was appropriate for the outbreak of 1990 to 1991 in Finland, but may provide unsatisfactory protection against B/Victoria/2/87-like viruses. Evidence is given that use of Madin-Darby canine kidney (MDCK)-grown virus as an antigen in the haemagglutination inhibition test (HI) may provide more reliable information about the protective antibodies than use of untreated or ether-treated egg-grown viruses. Significantly higher postvaccination and postepidemic antibody titres were recorded among subjects who exhibited the antibody before vaccination than among seronegative subjects. A significantly higher response rate among initially seronegative people than among seropositive people was recorded for antibody to B/Finland/150/90, but no clear evidence was obtained that the pre-existing antibody could have had a negative effect on the antibody production. PMID- 1502844 TI - [A step towards a nurse as chief. Interview by Maria Ejd]. PMID- 1502843 TI - [It takes time to learn all the new things. Interview by Maria Ejd]. PMID- 1502845 TI - [Refugees' nurse takes on the mother role: "sometimes you have to get angry". Interview by Kaj Nyman]. PMID- 1502846 TI - [It is more fun to go to work on a personal schedule]. PMID- 1502847 TI - [Work environment and participation provided under the same agreement. Interview by Maria Ejd]. PMID- 1502848 TI - [Accidents among elderly patients provided PhD degree in geriatric. Interview by Christer Agren]. PMID- 1502849 TI - [Reasonable conditions for education]. PMID- 1502850 TI - [Red Cross has charged for European Championship-football at Ullevi]. PMID- 1502851 TI - [Flexible doctors and effective care in consolidated clinics. Interview by Maria Ejd]. PMID- 1502852 TI - Foreign gene expression in yeast: a review. PMID- 1502853 TI - Application of a microbial sensor for determination of short-chain fatty acids in raw milk samples. AB - A microbial sensor system, based on the use of immobilized Arthrobacter nicotiana and an oxygen electrode, was applied to determine free short-chain fatty acids in raw milk samples and the result was compared with gas chromatography (GC) and a titrimetric method. The sensor response was linearly related to the concentration of short-chain fatty acids obtained by GC (n = 10, r = 0.92) and to the total concentration of free fatty acids obtained by titrimetric measurement (n = 10, r = 0.78). This result suggests that the present microbial sensor can selectively determine free short-chain fatty acids in raw milk samples and may be useful as a very fast detection method of rancidity in milk. PMID- 1502854 TI - Organochlorine pesticide and polychlorinated biphenyl residues in slaughtered and game animal fats from the northern part of Poland. AB - Pooled samples of the adipose fat of swine, cows, sheep, rabbit, ducks, geese, turkeys, wild boar, roe deer and stags collected from the northern part of Poland in 1987-88 were analysed for the presence of polychlorinated biphenyls (PCBs), hexachlorobenzene (HCB), hexachlorohexanes (HCHs), Dichlorodiphenyltrichloroethanes (DDTs), aldrin, dieldrin, heptachlor, heptachlor epoxide and chlordanes (CHLs). All the fats contained detectable, but low concentrations of organochlorine pesticides and PCBs. The mean PCB levels ranged from 9.2 to 47 micrograms/kg of which IUPAC nos. 138, 153, and 180 were dominating congeners in most of the samples. DDT concentrations were apparently lower in fat of the ruminants (45 to 84 micrograms/kg fat) while in rabbits, swine, turkeys and geese, it was from 79 to 140 micrograms/kg fat. Ducks and wild boar had the highest concentrations of 400 and 440 micrograms DDTs/kg fat, respectively. HCB was detected at concentrations ranging from 2.0 to 18 micrograms/kg fat. The total HCH concentration ranged between 15 and 77 micrograms/kg fat. Aldrin and heptachlor remained undetected while dieldrin was found only in some slaughtered species with a range of positive measurements up to 9.1 micrograms/kg fat. Similarly, heptachlor expoxide was traced up to 9.1 micrograms/kg fat and the residues of CHLs from 0.34 to 4.1 micrograms/kg fat. PMID- 1502855 TI - Isolation and enzymatic fragmentation of the coeliac-active gliadin peptide CT-1. AB - Investigations on the structure/toxicity relationships of gliadin peptides were continued with the coeliac-active gliadin peptide CT-1, which is derived from the N-terminal portion (residues 3-24 of the amino acid sequence) of alpha-gliadins [this journal (1986) 182:115-117]. CT-1 was produced by chymotryptic digestion and reversed-phase (RP) HPLC from the peptide fraction G3 [this journal (1992) 194:1-6] and digested with the proteases endoproteinase Glu-C, pancreatin, papain and thermolysin. The fragment peptides were separated by preparative RP-HPLC and characterized by amino acid analysis. On the basis of the specificity of the enzymes for CT-1 and the toxic effect of enzymatic hydrolysates of gliadin described in the literature, the significance of partial sequences, in particular of the sequence -Pro-Ser-Gln-Gln-Gln-Pro- for the coeliac-toxicity effect, is discussed. PMID- 1502856 TI - Selenium content of goat milk and its distribution in protein fractions. AB - This study reports on selenium distribution in goat milk. Skim milk was found to contain the major part (94%) of total milk selenium. The selenium distribution over casein and whey protein fractions depends on the separation method used, but irrespective of these methods, skim milk selenium is mainly associated with the casein fraction (greater than 69%). Approximately 9%, 7% and 24% of selenium is removed by dialysis (molecular cutoff 10-12 kDa) from skim milk, casein and whey respectively, indicating a major association of selenium with milk proteins. This observation is confirmed by selenium analysis of individual caseins and whey proteins isolated through ion-exchange chromatography and gel filtration. Selenium concentrations of the different isolated milk proteins show considerable variation (caseins: 294-550 ng Se/g; whey proteins: 217-457 ng Se/g). PMID- 1502857 TI - [Primary fibromyalgia syndrome--diagnostic statistics from primary care]. AB - The diagnosis of a primary fibromyalgia syndrome (PFS) which is supported mainly by clinical-anamnestic elements is, in many cases, finally established in the generalized stadium of the disease. It would be generally desirable to discover potentially endangered patients and to define "risk groups". During this study a case-by-case retrospective analysis of all available data sources (specialist's and hospital reports) has been conducted on 61 PFS-patients of a general practice. A further clarification diagnosis resulted in 75% of the cases suffering from general exhaustion. In over 50% of the examined patients diagnostic details referred to chronic lumbar and cervical spine syndromes. It is well possible that chronic cervical and lumbar spine as well as psychovegetative exhaustion syndromes predispose the generation of a PFS under consideration of a corresponding personality profile and other factors or it may even be a disease by itself. In every general practice the respective tender points of suspected patients should be examined and they should be questioned as to the basic symptoms of this disease. PMID- 1502858 TI - [Plasma GM-CSF concentrations in rheumatoid arthritis, systemic lupus erythematosus and spondyloarthropathy]. AB - Granulocyte-macrophage colony-stimulating factor (GM-CSF) is a multipotent hematopoietic growth factor, which is mainly produced by T-cells and stromal cells. Beside the stimulating effects on mature granulocytes, it induces the expression of HLA class II-antigen on synovial tissue-cells in patients with rheumatoid arthritis. The concentrations of GM-CSF in the plasma of 87 patients with rheumatoid arthritis, 48 patients with spondyloarthropathy, 17 patients with systemic lupus erythematosus (SLE), and 43 healthy control persons were investigated. We used an immunoradiometric assay (IR-MA) with a detection limit of 30 pg/ml to measure the GM-CSF concentrations in plasma. The GM-CSF levels of 29 patients with severe rheumatoid arthritis (366 +/- 61 pg/ml, p less than 0.05), 58 patients with moderate rheumatoid arthritis (376 +/- 44 pg/ml, p less than 0.0001), and of 17 patients with SLE (256 +/- 41 pg/ml, p less than 0.05) were elevated compared to the control group (174 +/- 18 pg/ml). No significant differences in the mean GM-CSF plasma levels between the patients with spondyloarthropathy (190 +/- 32 pg/ml) and the control group were found. GM-CSF concentrations as high as 1300 pg/ml were detected in the synovial fluids of patients with rheumatoid arthritis. GM-CSF concentrations in the plasma of patients with severe rheumatoid arthritis were correlated with the plasma concentrations of the soluble interleukin-2-receptor (sCD25) (R = +0.53). PMID- 1502859 TI - [Results of late synovectomy of the hip in juvenile chronic arthritis]. AB - The aim of this study was to examine the indication for total synovectomy of the hip in juvenile chronic arthritis. For this purpose, five children with six treated hips were followed up. At the time of synovectomy all patients were suffering from therapy resistance and progressive destructive coxitis, as a result of juvenile chronic arthritis. The procedure carried out must, consequently, be regarded as late synovectomy. At the time of the follow-up examination--at least 2 years after the operation--all patients had lasting relief from pain. The range of hip movement could not be improved, despite being accompanied by tenotomies and consistent rehabilitation in the postoperative years. The functional capacity in everyday life also failed to improve. During the post-operative radiographic follow-up the deterioration of the hips proceeded more rapidly than expected for this spontaneous course of treatment. The results lead to the conclusion that the relief of pain due to a late synovectomy of the hip is achieved at the expense of a rapidly progressive destruction of the joints. For this reason, the late synovectomy of the hip in juvenile chronic arthritis should be regarded as the last possibility where resistance to conservative therapy exists. PMID- 1502861 TI - Selective deafferentation of convergent inputs to trigeminal subnucleus caudalis: effects on calcitonin gene-related peptide distribution. AB - Electrophysiological studies (Sessle, 1987, 1991) suggest that trigeminal deafferenting injuries can cause an "unmasking" of existing but normally suppressed convergent inputs to the spinal trigeminal nucleus, including many that arise from the cervical spinal cord. However, the spatial arrangement of this projection has not been examined, particularly with reference to nociceptive components that might become involved in pathological changes leading to chronic pain. Therefore, the purpose of this study was to apply selective interruptions of the trigeminal and/or cervical primary afferent inputs to the spinal trigeminal subnucleus caudalis (Vc) in the cat, followed by (1) demonstration and quantification of axonal degeneration in the spinal trigeminal tract to determine the extent of trigeminal-cervical primary afferent overlap; and (2) an analysis of lesion-induced alterations in the distribution of calcitonin gene-related peptide immunoreactivity (CGRP-IR) in laminae I and II of Vc, since recent evidence strongly suggests that CGRP is involved in pathophysiological elevations of central nervous system neuronal excitability. Degenerating fibers were found throughout the spinal tract following a trigeminal rhizotomy or tractotomy, with the largest numbers adjacent to the rostral two-thirds of Vc, but with a significant number extending caudally to at least the level of C2. CGRP-IR was reduced or eliminated from the rostral one-third and periobex region of Vc, except for a dorsomedial zone that was minimally affected. Retention of CGRP-IR was greater at more caudal levels. Following a combined trigmeninal and cervical tractotomy, fiber degeneration was massive throughout the spinal tract, yet a population of small myelinated fibers persisted at 60 days after surgery. Concomitantly, CGRP-IR was profoundly reduced throughout Vc, except for a small dorsomedial zone of retention, which became more extensive caudally. A cervical tractotomy resulted in moderate numbers of degenerating fibers adjacent to the caudal one-third of Vc, and this number declined rostrally; however, degenerating fibers could be seen at the level of the obex. CGRP-IR was reduced in the dorsomedial and ventrolateral zones of Vc, particularly in its caudal one-third. Electron-microscopic analysis revealed a population of CGRP-IR boutons, most of which were of the simple axodendritic type with asymmetrical contacts. A few examples of axoaxonic contacts were observed. Loss of labeled boutons observed with the electron microscope was consistent with light-microscopic quantitative results. Those boutons that were retained were variable in size and displayed simple axodendritic contacts.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1502860 TI - [Bacterial sacroiliitis]. AB - We saw two cases of infectious sacroiliitis in young patients. The multi-various clinical symptoms, the predispositions, as well as the alteration of laboratory analyses are described. Further, we discuss problems of early diagnosis, diagnostic measures like x-ray, sonography, bone-scan, computerized tomography scan, magnetic resonance imaging, and their particular significance. Computerized tomography scan of iliosacral joints determined the further therapeutic procedure. In both cases, we prescribed cephalosporin-antibiotic cefotaxime sodium. PMID- 1502862 TI - Characterization of the percepts evoked by discontinuous motion over the perioral skin. AB - The capacity of human subjects to process information about discontinuous and continuous movement was evaluated. Constant-velocity brushing stimuli were delivered through aperture plates that rested lightly upon the mandibular skin. Each plate consisted of either two spatially separated, slit-like openings or a single continuous, longer opening. It was discovered that percepts of smooth apparent motion were achieved with the split apertures (i.e., from discontinuous movement) for only limited ranges of stimulus velocity. Moreover, the optimal velocity supporting smooth apparent motion increased with the separation between the slit-like openings. In a second series of experiments, subjects' ability to discriminate opposing directions of discontinuous and continuous movement was evaluated. It was found that subjects could derive directional information from percepts elicited by discontinuous movement. However, the capacity to discriminate opposing directions of continuous movement cannot be explained solely in terms of the ability to process information about the change in position of a stimulus from its onset to its offset. PMID- 1502863 TI - B scanning evaluation of allergic reactions with binary transformation and image analysis. AB - In order to characterize and quantify allergic skin reactions, 12 nickel sensitized women aged 18 to 45 underwent 5 patch tests with nickel sulfate in petrolatum at the following concentrations: 0.5, 1, 2, 3 and 5%. The tests, performed on volar forearm skin, were removed after a 24-h application. B scanning evaluations were carried out at the beginning and at 24, 48 and 72 h after patch test application using Dermascan C (Cortex Technology, Hadsund, Denmark). After obtaining echographic images, there were processed by a dedicated programme (Dermavision 2D, Cortex Technology, Hadsund, Denmark) enabling the selection of amplitudes of interest and the transformation into a binary colour system. By attributing one colour to a selected amplitude band, part of an image can be highlighted and assessed by a value corresponding to the number of pixels (picture elements). For the evaluation of the images, 2 bands were chosen. The first, ranging from 201 to 255 is able to highlight hyper-reflecting parts of the pictures (epidermis, lower part of the dermis); the second, ranging from 0 to 30, marks the hypo-echogenic part of the tissue, which is the site of inflammation. This method showed a progressive increase in the number of low reflecting pixels according to the nickel patch test concentration and to the elapsing of time. On the contrary, at 24 h there was a decrease in pixel values concerning the hyper reflecting band. This evaluation method proved useful in assessing the intensity of patch test responses. PMID- 1502864 TI - B scanning evaluation of irritant reactions with binary transformation and image analysis. AB - In order to characterize and quantify irritant skin reactions, 12 women aged 18 to 45 underwent 5 patch tests with sodium lauryl sulfate at the following concentrations: 0.5, 1, 2, 3 and 5%. The tests, applied on volar forearm skin, were removed after a 24-h application. Evaporimetry and B scanning were carried out at the beginning and at 24, 48 and 72 h after patch test application. Echographic recordings were performed by Dermascan C (Cortex Technology, Hadsund, Denmark). After the acquisition, the echographic images were processed by a dedicated software (Dermavision 2D, Cortex Technology, Hadsund, Denmark) enabling the selection of amplitudes of interest and the transformation into a binary colour system. By attributing one colour to a selected amplitude band, part of an image can be highlighted and assessed by a value corresponding to the number of pixels (picture elements). For the evaluation of the images, 2 bands were chosen. The first, ranging from 201 to 255 is able to highlight hyperreflecting parts of the pictures (epidermis, lower part of the dermis); the second, ranging from 0 to 30, marks the hypo-echogenic part of the tissue, which is the site of inflammation. The evaluation by means of the 201-255 amplitude band showed a marked decrease of the echogenicity of the epidermis which was more pronounced at 24-h determinations and for higher concentrations of sodium lauryl sulphate (SLS), whereas the increase in pixel numbers, shown by the 0-30 band, was slight and apparent only for high SLS concentrations. Echographic data and transepidermal water loss (TEWL) values showed a good correlation.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1502865 TI - Ultrastructural observation of calcification preceding new bone formation induced by demineralized bone matrix gelatin. AB - Demineralized bone matrix gelatin (BMG) was implanted into the skeletal muscle of Sprague-Dawley rats, and the resulting ultrastructural changes of the BMG were examined 3, 5, 7, 10, 15 and 20 days later. Most of the implanted BMG became calcified 7-20 days after implantation. Calcification ('acellular mineral deposition') was first observed as needle-shaped crystalline deposits in the BMG matrix on day 7 after implantation, which gradually increased in size and fused with one another in some deposits. They appeared to be divided into small partitions consisting of denatured collagen fibers unlike those of noncalcified BMG. Some deposits had electron-lucent areas in their center adjacent to well calcified peripheral areas, and the central area contained many collagen-like fibers and spherical vacuoles. Osteoblast-like cells were not present around these calcified deposits 7 days after implantation. After that, new bone formation was often seen near the area of acellular mineral deposition, and the fused calcified deposits remained until day 15 after implantation. The noncalcified BMG was mainly absorbed by macrophages, and the sites of acellular mineral deposition were absorbed by multinucleated cells resembling osteoclasts which were considered to be activated by the implants. Acellular mineral deposition probably started as calcium and phosphate deposits on some materials in the BMG matrix, and by heterogenic nucleation without osteoblasts or matrix vesicles, inducing bone formation. Thus the BMG may be not only a carrier of bone morphogenetic protein, gradually supplying it to the surrounding tissue but also a storage site for minerals that are indispensable for bone formation.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1502866 TI - Histo- and immunocytochemical characterization of the neurons of the mucosal plexus in the rat colon. AB - The mucosal plexus of the rat colon descendens is constituted of a network of nerves that, in contrast to most other segments of the digestive tract, contains also ganglia. The ganglia, consisting of neurons and glial cells, are located in the basal part of the lamina propria at distances between 100 and 1,200 microns. They are not vascularized. The neurons in these ganglia were characterized by means of: (1) the histochemical demonstration of acetylcholinesterase (AChE) activity, (2) the immunocytochemical identification of neurofilament proteins (NFP; 200 kD) and (3) their ultrastructure. The glial cells, which were AChE negative, could be distinguished from the neurons by differences in size and chromatin pattern. All neurons of the mucosal plexus reveal AChE activity in the perikaryon, but only parts of the axons are AChE positive. NFP-like immunoreactivity was detected in the perikarya but only in a minor part of the axons. These findings confirm previous light-microscopical observations and add new evidence for the existence of neurons (ganglia) in the mucosal plexus of the rat colon. PMID- 1502867 TI - Electron microscopy of the mucosal plexus of the rat colon. AB - The ultrastructure of neurons, glial cells and axons of the mucosal plexus of the rat colon descendens was studied. Serial semithin sections and a re-embedding technique were used in order to localize the ganglia. The ganglia are free of blood vessels and connective tissue. The ratio of neurons to glial cells is approximately 1. Ganglia and nerve strands are enclosed by a basement membrane, without a well-defined perineural connective tissue. The neurons show a structure similar to other enteric plexus. Synaptic contacts were observed frequently in the neuropil, where nerve endings and varicosities show a diverse outfit in vesicles. The glial cells, which contain immunocytochemically detectable glial fibrillary protein, possess the same ultrastructural attributes in the intra- and extraganglionic localizations. In the nerves, axonic profiles and varicosities appear in close relation with glial cells or their processes. The distance between the nerves and their target cells, i.e. the enterocytes, is 0.5 microns or more with interposed basement membranes and fibroblasts. PMID- 1502868 TI - Comparison of the effect of castration on the development of postural and non postural muscles of mice. AB - The effect of castration on the development of muscle mass of postural and non postural muscles was studied in 18 male mice (9 castrated, 9 uncastrated). Results obtained indicated that the castrated males grew faster and were bigger in body size and weight at maturity than the intact males. The bigger body size of castrated males was not due to larger muscle mass but was probably due to increased subcutaneous fat deposition. Atrophy of muscles usually observed following castration was significantly greater in the non-postural (biceps brachii) muscle of the forelimb as compared to the postural (triceps brachii) muscle of the forelimb. Conversely, the amount of reduction in muscle mass was similar in both postural (soleus) and non-postural (tibialis cranialis) muscles of the hindlimb. PMID- 1502869 TI - Cytoplasmic filaments in the endothelial cells of the sheathed capillary: an ultrastructural and immunocytochemical study in the pig spleen. AB - Cytoplasmic filaments of the endothelial cells of sheathed capillaries in the pig spleen were identified and their ultrastructure was studied. Two types of cytoplasmic filaments were found: intermediate filaments (diameter: 10 nm) which filled most of the interior of the cells, and thin filaments (diameter: 5 nm) which were located just beneath the cell membrane and filled the lateral cytoplasmic processes. In immunocytochemical preparations, the intermediate filaments were positive for vimentin and desmin, and were negative for keratin. Staining of the thin filaments with heavy meromyosin resulted in arrowhead formations. These observations suggest that the intermediate filaments maintain the cytoarchitecture, possibly protecting the cell from structural alterations induced by blood pressure changes. Concurrently, thin filaments may facilitate the passage of red blood cells and blood platelets through the interendothelial fenestrae of the sheathed endothelial cell to the reticular meshwork in the capillary sheath. PMID- 1502870 TI - Ultrastructural and morphometric study of hepatocytes from near-term minipig fetuses exposed to ethanol in vivo. AB - Hepatocytes of near-term minipig fetuses were studied after their mothers had received a daily addition of 3 g/kg body weight of ethanol to the ordinary sufficient fodder during the last half of pregnancy. The ethanol-exposed hepatocytes were evaluated ultrastructurally and morphometrically, and compared with hepatocytes of unexposed fetuses. The present results show that hepatocytes of near-term fetuses, exposed to a high concentration of ethanol for a long period exhibit neither qualitative nor quantitative changes. This is in contrast to maternal hepatocytes which show an adaptation of cellular components to ethanol by developing increased volume densities of mitochondria and smooth endoplasmic reticulum and a decreased volume density of glycogen. PMID- 1502871 TI - Central projection of the sensory fibres of the recurrent laryngeal nerve of the cat. AB - There have been few studies of the central projection of the sensory fibres of the recurrent laryngeal nerve into the medulla oblongata. In the present study terminal degeneration was observed in both the nucleus of the tractus solitarius and the nucleus of the spinal tract of the trigeminal nerve after transection of the nerve and after injection of a lectin, Ricinus communis agglutinin (RCA). Degeneration was observed to be more extensive after RCA injection than after nerve transection. In both instances, however, degeneration was observed bilaterally. PMID- 1502872 TI - Further examination of the basicranial anatomy of the megachiroptera: a reply to A.J. King. AB - Four basicranial characters supporting a single origin of megachiropterans and microchiropterans have been identified by Wible and Novacek. King was not able to find two of these characters in specimens of the megachiropteran Pteropus and concluded that these characters be rejected in analyses of chiropteran phylogeny. To address King's claims, the two characters in question (regarding the tegmen tympani and ramus inferior of the stapedial artery) are documented here for Pteropus. The discrepancies between this report and King's appear to result from different criteria for identifying the tegmen tympani. Employed here are the criteria generally accepted by students of the mammalian chondrocranium. PMID- 1502873 TI - Variations in lectin localization in different parts of the bovine heart. AB - In order to study the distribution of endogenous sugar-binding proteins (lectins) in various areas of the adult bovine heart, we used a battery of biotinylated neoglycoproteins. These tools expose carrier-immobilized carbohydrate moieties as ligands for receptor detection. Characteristic staining patterns depending on the type of carbohydrate ligand were observed in all constituents examined. Comparison to data obtained for lectin distribution in the respective areas of the human heart indicate that the localization of certain types of endogenous sugar receptors can exhibit species-dependent variations. PMID- 1502874 TI - Biochemical and cytochemical studies of preadipocyte differentiation in serum free culture of porcine stromal-vascular cells: interaction of dexamethasone and growth hormone. AB - Stromal-vascular cells from adipose tissue of pigs 5-7 days of age were grown in serum for 2-3 days and switched to serum-free (insulin, transferrin and selenium) conditions +/- test hormones for 6-7 days. The interaction of dexamethasone (DEX) and human growth hormone (hGH) was evaluated since glucocorticoids augment and hGH antagonizes the effect of insulin. Low levels (1-10 nM) of DEX with insulin doubled (p less than 0.05) specific activity of glycerol phosphate dehydrogenase (GPDH) and doubled (p less than 0.05) the number of detectable fat cells relative to insulin alone. DEX with insulin enhanced the morphological differentiation of preadipocytes and markedly increased fat cell cluster numbers in the presence of hGH. Furthermore, 1-10 nM of DEX partially blocked (p greater than 0.05) the inhibitory effect of 10 nM hGH on GPDH activity, but 1-100 nM DEX had no effect (p greater than 0.05) on the ability of hGH to compromise lipid deposition. DEX alone (no insulin or hGH) induced the appearance of esterase-reactive but lipid free cells. Cells with these characteristics were increased in number by DEX in the presence of hGH but were nearly absent in the presence of insulin and DEX. Therefore, transient exposure to GH in vivo may have no permanent effect on adipose tissue development in the continued presence of glucocorticoids. PMID- 1502875 TI - Ossification of the human fetal ilium. AB - Ossification of the ilium is similar to that of a long bone. It possesses three cartilaginous epiphyses and one cartilaginous process. Moreover, it undergoes peculiar osteoclastic resorption, comparable with that of the cranium bones. Asymmetrical ossification of the ilium, haversian bone remodelling and apposition of chondroid tissue posterosuperiorly to the acetabulum most probably emphasize the importance of mechanical factors in the morphogenesis of the hip bone during fetal life. PMID- 1502876 TI - A semiquantitative scale for histologic grading of articular cartilage repair. AB - This laboratory has developed a semiquantitative scale for grading the natural healing process of defects drilled into articular cartilage. The scale is composed of four parameters: percent filling of the defect, reconstitution of the osteochondral junction, matrix staining and cell morphology; it has a score range from 0 (best) to 14 (worst). The scale was used to evaluate the healing of defects drilled into rabbit knee articular cartilage at 2, 14, 30, 60 and 120 days after surgery. No statistically significant difference in the graded score was found between the two different defect sizes (2.7 and 1.5 mm). However, the differences in score observed between specimens from different sacrifice times were significant (p less than 0.01). Currently many investigators are manipulating cartilaginous lesions in an attempt to improve healing, and this scale will provide a means for quantitatively comparing results from control and experimental groups. PMID- 1502878 TI - Lewy bodies in Parkinson's disease are recognized by antibodies to complement proteins. AB - The substantia nigra (SN) in 11 Parkinson's disease (PD) patients and 5 neurologically normal controls was examined immunohistochemically using antibodies to various proteins of the complement system. In PD, but not in control SN, intra- and extraneuronal Lewy bodies and dendritic spheroid bodies were stained with anti-human C3d, C4d, C7 and C9 antibodies, but not with antibodies to C1q, fraction Bb of factor B or properdin. Axonal spheroid bodies in the nigrostriatal tract were not stained by any of the complement antibodies. However, complement-activated oligodendroglia were revealed by anti-C3d and anti C4d antibodies in the PD substantia nigral area. These data indicate that some pathological structures in PD activate the classical complement pathway. PMID- 1502877 TI - Neuropathologic findings after liver transplantation. AB - Neuropathologic findings are described in 37 patients autopsied after one or more orthotopic liver transplants. Gross or microscopic lesions were observed in almost all patients, including anoxic-ischemic change, hemorrhages and/or infarcts, and opportunistic infections by fungi (most commonly Aspergillus) and rarely viruses (cytomegalovirus). Central pontine and extra-pontine myelinolysis was commonly observed, and appeared to result from severe multifactorial metabolic abnormalities in the perioperative period. Low-grade (microglial nodule) encephalitis without an obvious pathogen was often encountered. Common clinical neurologic abnormalities included encephalopathy, seizures (myoclonic, focal or generalized), obtundation and coma. These were found more commonly than focal findings, but clinical features in a given patient were not uniformly predictive of underlying neuropathologic change. PMID- 1502879 TI - Gerstmann-Straussler syndrome--a variant type: amyloid plaques and Alzheimer's neurofibrillary tangles in cerebral cortex. AB - This report presents a variant of Gerstmann-Straussler syndrome (GSS). A 53-year old female had developed slowly progressive dementia and atactic gait since the age of 45. No myoclonic jerks and periodic synchronous discharges were observed throughout the illness. The neuropathological study revealed that many amyloid plaques and widespread Alzheimer's neurofibrillary tangles (NFTs) appeared in the cerebral cortex. Characteristically, the plaques reacted with anti-prion protein and none of them reacted with anti-beta protein, and they were made of many components, including amyloid cores, macrophages laden with lipid granules and/or degenerated neurites. Neuropil threads were seen mainly in amyloid plaques. Moreover, plaques appeared which were confluent and laminar in arrangement in the fifth and sixth cortical layers and had a close relationship to the neuronal loss. There was no spongiform change in the cerebral cortex or cerebellum. The cerebellum was almost intact except for a few amyloid plaques. Ultrastructurally, some of the plaques simulated kuru plaques and others had many degenerated neurites possessing paired helical filaments and other accumulated organelles. GSS has been proposed to include cases with progressive ataxia, dementia and massive multifocal plaques in the brain with or without cerebral spongiform changes. The case presented here is a very peculiar case of GSS. Recently, similar cases have been reported in some large families, diagnosed as familial Alzheimer's disease. These cases may be a telencephalic form with numerous NFTs of GSS. PMID- 1502880 TI - Distribution of human immunodeficiency virus (HIV) in the CNS of children with severe HIV encephalomyelopathy. AB - The presence and distribution of human immunodeficiency virus (HIV) were examined in the CNS of two children with severe HIV encephalitis and myelitis. Using polymerase chain reaction-mediated DNA amplification and subsequent Southern analysis, proviral HIV gag sequences were identified in brain tissue of both patients. In situ hybridization using antisense oligonucleotide probes revealed abundant HIV gag and env/nef RNAs selectively in areas with histopathological evidence for HIV-induced tissue damage. The spinal cord of one patient exhibited a striking subpial accumulation of HIV RNAs strongly suggestive of a liquorigenic spread of the infection. HIV RNAs were typically associated with cells of the monocyte/macrophage lineage, as shown by a combined immunohistochemical and in situ hybridization procedure. The present study supports the view that the pattern and distribution of HIV-induced brain lesions is largely determined by the extent of focal HIV replication within the CNS. PMID- 1502881 TI - Distribution of cortical neurofibrillary tangles in progressive supranuclear palsy: a quantitative analysis of six cases. AB - Progressive supranuclear palsy is characterized neuropathologically by the presence of high densities of neurofibrillary tangles in several subcortical structures. In some cases, neurofibrillary tangles have also been described in the cerebral cortex. We performed a quantitative regional and laminar analysis of the distribution of these lesions in six cases of progressive supranuclear palsy. We observed that the neurofibrillary tangle distribution in the cerebral cortex was largely confined to the hippocampal formation. In particular, in all the cases neurofibrillary tangles were observed in the granule cell layer of the dentate gyrus. In the prefrontal and inferior temporal cortex, neurofibrillary tangles were predominantly distributed in layers II and III. In addition, there were moderate-to-high neurofibrillary tangle densities in the primary motor cortex. This localization pattern contrasts with the neurofibrillary tangle distribution observed in the cerebral cortex of Alzheimer's disease cases, where tangles are denser in layer V than in layer III, and where the primary motor cortex and the dentate gyrus are usually not involved. These results suggest that specific elements of the cortical circuitry might be differentially vulnerable in progressive supranuclear palsy as compared to Alzheimer's disease. PMID- 1502882 TI - Intracerebral distribution of albumin after transient cerebral ischemia: light and electron microscopic immunocytochemical investigation. AB - The blood-brain barrier breaks down following cerebral ischemia, but the exact sequence of events for extravasation of serum proteins and their parenchymal distribution remain uncertain. We studied the distribution of serum albumin in the hippocampus of the gerbil brain using light and electron microscopic immunocytochemical techniques. With light microscopy, there was no reaction for albumin for the first 12 h after unilateral common carotid artery occlusion for 10 min and reperfusion. At 12 h, the reaction was weak and limited to the neuropil in the subiculum-CA1 region (between the subiculum and the medial CA1 region). After 24 h, the reaction became intense in the neuropil and neuronal perikarya in the subiculum-CA1 and medial CA1 regions. The electron microscopic immunocytochemical study of the subiculum-CA1 and medial CA1 regions revealed electron-dense immunoprecipitates in the extracellular space and the peripheral part of the apical dendrites as early as 30 min after reperfusion and in the astrocytic cytoplasm after reperfusion for 1 h. However, immunoprecipitates were not found in the neuronal perikarya until after reperfusion for 24 h. The present study demonstrated prompt appearance of albumin in the extracellular space of the brain parenchyma after re-establishment of cerebral circulation and prompt accumulation in the peripheral part of the dendrites with spreading to neuronal perikarya, likely in the process of degeneration and death. PMID- 1502883 TI - The growth of two murine hemangioendotheliomas intracranially, subcutaneously, and in culture, and their comparison with human cerebellar hemangioblastomas: morphological and immunohistochemical studies. AB - Two thorium dioxide-induced murine hemangioendotheliomas, 42021 TCT and 44347 TST, were grown subcutaneously (for up to 22 and 15 passages respectively) or intracranially (single passage) and were adapted to culture as a monolayer and, in a limited fashion, in an organ culture system or in rotary suspension. They remained viable and malignant following 20-21 years of storage in liquid nitrogen, and had ultrastructural similarities to human hemangioblastomas. The murine tumors were positive for Griffonia (Bandeiraea) simplicifolia isolectin B4 binding, establishing their endothelial nature; however, unlike human hemangioblastic tumors, they did not cross-react with antisera to human factor VIII or fibronectin and they did not demonstrate Ulex europaeus type I lectin (UEA I) binding (as is also the case for non-neoplastic murine vascular endothelial cells). A variety of morphological cell types in cultures derived from the tumors were also positive for Griffonia (Bandeiraea) simplicifolia isolectin B4 binding. Both murine hemangioendotheliomas, when implanted in the cerebrum, were potent inducers of reactive gliosis, but there was no evidence of uptake of glial fibrillary acidic protein. Unlike the human cerebellar hemangioblastomas, murine tumors were malignant and invasive and did not contain stromal cells, nor did they demonstrate Weibel-Palade bodies or extensive pinocytotic activity. Thus, the murine tumors appear to more closely resemble angiosarcomas or epitheloid hemangioblastomas than the cerebellar hemangioblastomas. PMID- 1502884 TI - Changes in the choroid plexus, responses by intrinsic epiplexus cells and recruitment from monocytes after experimental head acceleration injury in the non human primate. AB - We have examined, by scanning and transmission electron microscopy, morphological changes in the choroid plexus of the lateral ventricles of the non-human primate brain after lateral head acceleration. We demonstrate passage of plasma and blood cells either through tears in blood vessels and the choroidal epithelium, or through the cells of the choroidal epithelium, 20 min after injury, together with morphological changes in that epithelium. At 3 and 4 h small cells with a reniform nucleus accumulate in the connective tissue core of the choroid plexus. We suggest that these are monocytes. At 6 and 12 h cells can be seen in enlarged intercellular spaces within the choroidal epithelium. These cells possess surface ruffles and we suggest that they are monocytes differentiating into macrophages and epiplexus cells. Further evidence for transepithelial migration of monocytes/macrophages is obtained at 7 days. However, at 28 days all blood has been removed from the surface of the choroid plexus and epiplexus cells possess an appearance typical of that in uninjured animals. The possible sources of epiplexus cells are discussed with reference to studies of responses after brain insult and of development. We have obtained no evidence in support of emperipolesis by monocytes through the choroidal epithelium. We suggest that monocytes/macrophages migrate, via an intercellular route, to differentiate into epiplexus cells, thus providing additional numbers of epiplexus cells after head injury. PMID- 1502885 TI - Anchorage densities associated with hemidesmosome-like structures in perivascular reactive astrocytes. AB - Electron microscopical examination of devastated and reticular gliosis-replaced areas of two human brains revealed novel anchorage densities (ADs) associated with hemidesmosome-like structures (HDLSs) in perivascular astrocytes; the densities, 200-300 nm away from the cell membrane overlying the basal lamina, ran parallel to the membrane. The subplasmalemmal ADs usually received fibrils from the main stream of the deeply located glial fibrils, and sent isolated 13- to 16 nm fibrils roughly perpendicularly to the unusually prominent and frequently continuous HDLSs on the inner leaflet of the cell membrane, undercoated by a thickened basal lamina. The variable profiles of the ADs indicated that they were cell membrane-connected sheets or meshes that were virtually completely composed of bundles of glial fibrils intercrossing at variable angles or running roughly parallel to one another. All these findings suggest that the ADs may provide a significant support to the cell membrane facing the perivascular space. PMID- 1502886 TI - The effect of nerve crush and botulinum toxin on lead uptake in motor axons. AB - After lead (Pb) is injected into striated muscle it binds to the sarcolemma of the neuromuscular junction (NMJ) and crosses into the terminal axons of motor neurons. To find out whether this intra-axonal accumulation of Pb is due to active transport or to diffusion down a concentration gradient, Pb uptake into motor axons of mice was studied at active and inactive NMJs. Twenty-four hours after sciatic nerve crush, 0.1 ml of 5% lead nitrate was injected into the tibialis anterior muscle and 30 min later the location of Pb was sought with electron microscopy and X-ray elemental analysis. A greatly reduced amount of Pb entered the axons after nerve crush compared to non-nerve crush animals, indicating that an active NMJ is required for intra-axonal Pb accumulation. To test if Pb could be entering the axon via recycling vesicles, botulinum toxin (BoTx) was injected into the muscle 24 h before Pb injection. There was no difference in intra-axonal Pb uptake in control and BoTx-injected animals, indicating that Pb is unlikely to use recycled vesicles to enter the axon. PMID- 1502887 TI - Radio-immunotargeting in experimental animal models of intraperitoneal cancer. AB - The field of immunotargeting, and the challenges met when this technique is applied in experimental animals or in patients, are reviewed. Even with highly specific monoclonal antibodies, non-specific uptake in normal tissues and high background level of unbound radioactivity in blood and extravascular body fluids remain significant problems. Further experimental work in animal model systems is needed to bring this technique from the state of being an experimental method, with limited clinical application, to a routine diagnostic or therapeutic method. Different animal models are available, and their potential for elucidation of the various methodological problems in radio-immunotargeting are discussed in the present paper. In our laboratory, two intraperitoneal models were devised, having relevance for gynecologic and other forms of intraperitoneal malignancies. These models were elaborated with special emphasis on the possibility for exact measurement of important parameters in immunotargeting reactions. In the first model, hybridoma cells are inoculated intraperitoneally to mimic intraperitoneal carcinomatosis, and the monoclonal antibody produced by the hybridoma is used as serum tumor marker. In the second model the tumor cells are contained within intraperitoneally implanted micropore chambers, resembling a localized tumor. An artificial tumor like this allows control with the antigen load in the target, and measurement of the concentration of the injected antibody in the fluid within the target. PMID- 1502888 TI - Oncogene and growth factor expression in ovarian cancer. AB - The varying tumor-biological behavior of ovarian carcinomas probably influences both their operability and response to chemotherapy, which are the most relevant prognostic factors. The phenotype of different ovarian carcinomas is obviously associated with an activation of the EGF/TGF-alpha signal pathway, including c myc and c-jun expression. Analysis of EGF-R, TGF-alpha, c-myc and c-jun expression in 33 stage III/IV, and 2 stage I/II ovarian carcinomas with biochemical, molecular-chemical and immunohistochemical methods showed a correlation between the mRNA and protein levels of EGF-R and TGF-alpha for tumors with low or high expressing rates. However, the concentration of measurable free EGF-Rs seems to depend on the amount of TGF-alpha expression by the tumors. The EGF-R binding ligand TGF-alpha is produced by epithelial tumor cells; stromal cells are usually TGF-alpha-negative, as shown by immunohistochemistry. High expression rates of EGF-R. TGF-alpha and c-myc were detected in 6, 7, and 10 out of 35 ovarian carcinomas, respectively. C-jun mRNA was detected in 18/19 cases studied. Non-malignant tissues originating from myometrium or ovary expressed no (or only small amounts of) EGF-R or TGF-alpha mRNA, whereas a high c-myc expression was found in 1/7 normal myometria, and in 2/5 normal ovaries. There was no strong correlation between EGF-R/TGF-alpha and c-myc/c-jun expression.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1502889 TI - Oncogenesis in ovarian cancer. AB - Tumorigenesis is a multistep process involving mutations of dominantly acting proto-oncogenes and mutations and loss-of-function mutations of tumor suppressor genes. Some of these mutations may be inherited, but most of them are acquired. Models for the sequential steps of the genetic changes involved in tumor development have been proposed for certain cancers, such as colon cancer. In the case of ovarian cancer, relatively little is known about the genetic events associated with the initiation or subsequent progression and metastases of the tumor. Cytogenetic analysis has revealed a high incidence of both structural and numerical chromosome changes, and the extent of these changes seems to increase with tumor progression. Oncogene activations of the proto-oncogenes K-ras, c-myc and c-erbB-2 have been found more frequently in aggressive ovarian tumors and may be associated with poor survival. Tumor-specific allele loss involving putative tumor suppressor genes has been observed for loci at chromosomes 11p, 17p, and 17q,--loci commonly deleted in other cancers too. A relatively high incidence of allelic loss on chromosome 6q appears to be specific to ovarian carcinoma. Familial breast/ovarian cancer has been suggested to map to chromosome 8q. Recently we have found a germ-line mutation in the tumor suppressor gene p53 in a family with breast- and ovarian cancers, indicating that this is the predisposing gene in this family. Genetic changes important for the etiology of ovarian cancers seem to involve both somatic mutations of oncogenes and somatic or germ line inactivation of tumor suppressor genes. PMID- 1502890 TI - Intracellular actions of steroid hormones and their therapeutic value, including the potential of radiohalosteroids against ovarian cancer. AB - The biological activities of steroid hormones are effected via intracellular receptors. The receptors are part of a ligand-activated family of transcription regulator proteins that are critical for steroid-regulated cell differentiation. With recombinant cDNA technology, yeast and cultured animal cells can be made to express mammalian cDNA steroid receptors from cDNA clones that contain deletions and substitutions. Among the leading problems addressed in these models is the characterization of sequences that promote association or interaction with other transcription regulating molecules, including oncogene products. Recently it has been found that heat shock proteins may serve not only to stabilize the receptor proteins but also to precondition the activation imparted by ligand binding. Aberrant receptor proteins can be found in ovarian cancer. Whether aberrant receptor proteins are associated with transformation in general or with a variable clinical response to steroidal or anti-steroidal therapy is not known. Even after chemotherapy, steroid receptors are expressed in the metastases of ovarian cancers seen clinically, and they may have potential uses for localization and treatment of receptor-rich cancers. Radioligand pharmaceuticals appropriate for imaging or for site-directed radiocytotoxicity can be sequestered to the nuclei of receptor-rich cancers. Initial clinical imaging and therapy trials with such pharmaceuticals have been approved and begun. In the use of halogenated estrogen radiopharmaceuticals, liver metabolism and enterohepatic recirculation are important considerations. Ascites prolongs retention of a radiohalogenated estrogen in the abdominal cavity. Distant metastases have been localized with [123I]-estrogen in breast cancer patients in pre-operative procedures. Receptor-mediated cytotoxicity occurs when estrogen receptor radioligand pharmaceuticals that are Auger electron emitters are used in vitro. PMID- 1502891 TI - Inhibin as a marker for granulosa cell tumor. AB - In order to determine whether serum-immunoreactive inhibin could constitute a biochemical marker for the presence and progression of ovarian granulosa cell tumors and their metastases, we measured immunoreactive inhibin concentrations in series of serum samples obtained from 8 patients with granulosa cell tumor. Six series were tested in retrospect. From these, three came from patients who had been treated with an abdominal hysterectomy and bilateral salpingo-oophorectomy. In the 2 patients with residual or recurrent disease, inhibin was elevated, 4 and 20 months respectively before clinical manifestations of recurrence became evident; it reflected the effects of secondary therapy. Inhibin remained undetectable in one patient who was free of disease during 11 years of follow-up. Inhibin concentrations were also inappropriately increased in 2 of 3 women with amenorrhea and infertility resulting from small granulosa cell tumors. After removal, inhibin concentrations became normal and fertility resumed. Fertility also returned in the third patient. There was a significant negative correlation between the serum inhibin and FSH concentrations, consistent with autonomous production of inhibin by granulosa cell tumors. It is concluded that granulosa cell tumors have the capacity to produce inhibin. In retrospect, inhibin proved to be a marker for both primary and also recurrent and residual disease. PMID- 1502892 TI - Prognostic indices in ovarian cancer. Their significance in treatment planning. AB - Ovarian cancer exhibits a wide spectrum of behavior, the effectiveness of therapies varies and the circumstances of patients differ. Better outcomes will require more selective treatment strategies considerate of these variables. 1. The need for treatment As long as outcome is affected more by disease than by treatment, survival will be determined by the bulk and growth-rate of residual tumor-prognostic factors reflect these. They indicate the need for treatment, but not whether benefit is likely. FIGO stage is the international standard, but this alone is inadequately predictive. Grade reflects virulence, but subjectivity has limited its usefulness. Newer quantitative pathology techniques (such as DNA ploidy) more reproducibly reflect behavior. Prognostic factors can be used to define subsets of patients at differing degrees of disease risk. 2. Efficacy of treatment No response predictors are yet of practical use in selecting primary chemotherapy on an individual basis. Generally, response is more likely if the tumor is less extensive and if dose and treatment frequency are higher. Monitoring biomarkers can more quickly identify those with a suboptimal response who may require a change or discontinuation of treatment. Re-laparotomy has limited usefulness. Response predictors for second-line treatment (e.g. the failure-free interval) are available and also have implications for new drug testing. 3. Suitability of treatment Advanced age or serious additional illness may render intensive treatment inappropriate. The informed patient's wishes are of prime importance. An evolving strategy of selective management is described. PMID- 1502893 TI - Unsettled questions regarding ovarian cancer. PMID- 1502894 TI - Role of carboplatin in ovarian cancer. Current results and thoughts for the future. AB - Carboplatin is a cisplatin analog that causes less nephrotoxicity, neurotoxicity and nausea and vomiting than its parent compound. In prospective clinical trials, carboplatin has been shown to be as active, but less toxic, than cisplatin in previously untreated patients with advanced ovarian cancer. However, carboplatin has not led to improved survival, compared with cisplatin. Studies are in progress to reduce the dose-limiting myelo-suppression of carboplatin in order to increase the dose intensity. In addition, new carboplatin combinations are also to be evaluated in clinical trials. The molecular basis for resistance to platinum compounds is also undergoing study and future clinical trials will evaluate modulations of resistance. PMID- 1502895 TI - The controversial 'second-look' laparotomy. AB - To determine optimal indications for and clinical assessment of the significance of relaparotomy, the data of 304 women with malignant ovarian tumours (of epithelial origin, predominantly, 72%) who had undergone a 'second-look' operation were analysed. 'Second-look' relaparotomies were performed 10-22 months after the initial operation, on the following clinical indications: 1) clinical remission after initial combined treatment (surgery + chemotherapy) in cases where malignant cells are found at systematically performed cytological examinations of ??? or lavage from peritoneal surfaces of the Douglas cul-de-sac plus high levels of CA 125 in blood serum (8 patients with stages I and II, FIGO classification); 2) remission after adequate combined treatment and following 6 10 cycles of polychemotherapy, in order to decide whether to abandon or continue with treatment (13 patients with stages III and IV); 3) clinical remission following initial operation which was voluminously non-radical (117 patients); 4) suspicion of tumour recurrence after adequate combined treatment (114 patients); 5) no suspicion of cancer recurrence, though with ventral hernia or other pathology requiring relaparotomy (22 patients). Complications arising at the 'second-look' operation or during the postoperative period were observed in 29 of the 304 patients (9.5%), giving a postoperative mortality of 0.9%. According to experience, the positive significance of 'second-look' operations to optimize treatment of patients with malignant ovarian tumours is obvious. PMID- 1502896 TI - What do CA 125 and other antigens tell us about ovarian cancer biology? AB - CA 125 is an antigenic determinant on a high molecular weight glycoprotein. A monoclonal antibody has been produced which recognizes this, and allows us to measure the expression of CA 125 in serum. Tissue distribution of the CA 125 determinant is most commonly seen in serous tumors of the ovary, with highest levels in borderline and frankly malignant serous cystadenocarcinomas. Occasionally cancers of the breast, gastrointestinal tract, and kidney will show elevated levels of CA 125. Normal tissues which show varying levels of CA 125 include decidual tissue and structures derived from celomic epithelium. CA 125 is clearly tumor associated, but not tumor specific. Quantitative correlation of CA 125 levels with tumor volume has not been demonstrated. This observation limits the clinical usefulness of CA 125 as a screening tool, particularly in premenopausal patients who do not have a diagnosis of ovarian cancer. An undetectable level of CA 125 antigen does not rule out the presence of an early ovarian cancer. When CA 125 is used to monitor disease state in patients with known ovarian cancers (whose tumors do express CA 125), changes in levels of CA 125 do correlate with gross changes in tumor volume. Good prognostic significance is attributed to a rapid decline in CA 125 levels following induction chemotherapy in patients with advanced ovarian cancer. However, an undetectable serum level of CA 125 does not predict clinical cure for a patient with ovarian cancer. Further clinical studies continue in the use of CA 125 as a screening tool and as a means to monitor treatment responses of known ovarian cancer. PMID- 1502897 TI - DNA flow cytometry as a new prognostic factor in ovarian malignancies. A review. PMID- 1502898 TI - Aminoterminal propeptide of type III procollagen in ovarian cancer. A review. AB - The concentration of the aminoterminal propeptide of type III procollagen (PIIINP) in serum is a measure of the activity of the metabolism of type III collagen, which is a major constituent of soft connective tissues and of the connective tissue stroma of solid tumours. In advanced ovarian carcinoma, serum PIIINP serves as a tumour-associated antigen, its changes reflecting and preceding changes in the clinical behaviour of the malignancy. Elevated values of serum PIIINP are also observed in endometrial and cervical malignancies, though less frequently than in ovarian tumours. Very high concentrations of PIIINP are found in ovarian carcinoma ascites, suggesting an ongoing fibro-proliferative reaction in the peritoneal cavity as a response to the tumour. PMID- 1502899 TI - Mucosal defense mechanism in health and disease. Role of the mucosal immune system. AB - The mucosal immune system is characterized predominantly by the secretory antibody response and gut-associated lymphoid tissue, cellular part of the mucosal immune system. The secretory antibody system depends on local production and selective epithelial transport of secretory IgA and IgM. Furthermore, secretory antibodies and interactions between the intestinal epithelium and T cells are involved in the mucosal down-regulation of the systemic immune system. Neuropeptides play a crucial role in the regulation of mucosal immune responses. It is possible that impairment of the mucosal immune response contributes to the pathogenesis of various intestinal diseases, such as inflammatory bowel disease. Until recently, however, mucosal immunity received relatively little attention from both basic and clinical scientists. Further research on mucosal immunity seems to have promise in helping to provide new understanding of the immune mechanisms and pathogenesis of several gastrointestinal and systemic diseases. PMID- 1502900 TI - Biological aspects of pituitary tumors induced by synthetic salmon calcitonin (TZ CT) in Sprague-Dawley rats. Immunohistochemical and ultrastructural studies. AB - Rat pituitary tumors induced by synthetic salmon calcitonin (TZ-CT) were studied by the indirect peroxidase-labeled antibody method, together with ultrastructure and serum hormone measurement. Immunohistochemically, TZ-CT-induced pituitary tumors showed staining for only rLH alpha subunit, and were negative for other peptide hormones including GH, PRL, alpha MSH and ACTH, and the beta subunit of glycoprotein hormones. Electron microscopic examination showed that the majority of tumor cells possessed numerous small secretory granules, 100 to 200 nm in diameter. The serum PRL concentrations of rats with TZ-CT-induced pituitary tumors were markedly elevated, but not beyond 130 ng/ml. From our data, TZ-CT induced pituitary tumors are considered to be endocrinologically inactive and to produce alpha subunit. Furthermore, these tumors are thought to be potentially useful models of alpha subunit-producing pituitary tumors in humans. This is the first report to document the tumorigenesis of alpha subunit-producing pituitary tumors in rats after long-term treatment with calcitonin. PMID- 1502901 TI - Fundamental morphological changes in human olivary hypertrophy. AB - Morphological features of neurons in human inferior olivary nuclei were studied in 6 autopsied patients with dentato-olivary pathway lesions, who had survived for between 6 days and 15 months. Central chromatolysis-like neuronal enlargements were already present in the acute cases. Electron microscopy revealed round, homogeneous and electron-dense granules, varying in diameter from 0.15 micron to 2.5 microns, occurring frequently within the rough endoplasmic reticulum (ER) in the chromatolytic neurons of all 6 patients. No similar granules were observed in 6 controls. The vacuoles were due to dilatation of the rough ER, and often contained floccular materials. Neurofilamentous hyperplasia in the neurons was more frequently seen in the chronic cases. These findings suggest that the fundamental changes in the neurons in olivary hypertrophy occur within the rough ER. PMID- 1502902 TI - Histologic changes in Graves' thyroid gland after 131I therapy for hyperthyroidism. AB - The effect of 131I therapy was examined in 13 thyroid glands affected by Graves' disease 3 to 29 years after irradiation for hyperthyroidism. All of the patients had clinically palpable thyroid nodules. Two patients were in a latent hypothyroid, 6 in a euthyroid and 5 in a hyperthyroid state. The microscopic changes in the thyroids showed a pattern of multiple adenomatous nodules with cystic changes, marked oxyphilic cell changes with nuclear atypism and various degrees of chronic thyroiditis. Immunohistochemical staining for TG and T4 was negative to mildly positive in these oxyphilic cells and entirely negative for EGF and CEA. The DNA ploidy pattern was diploid pattern in 6 cases. One papillary type microcarcinoma occurred, but there was no evidence of a relationship between the tumor and the irradiation. The pathologic findings in Graves' thyroid gland after 131I therapy are not specific, but pathologists should differentiate this lesion from adenomatous goiter, which occurs with no apparent cause, or from thyroid carcinoma because of the marked nuclear atypism of this lesion. PMID- 1502903 TI - Neonatal Legionnaires' disease. Histopathological findings in an autopsied neonate. AB - A neonatal case of legionnaires' disease (LD) is reported. A male neonate was admitted to our hospital with high fever and dyspnea, which had started 5 days after birth, and died due to severe pneumonia at 10 days old. An autopsy revealed small areas of granular consolidation scattered diffusely in the bilateral lungs. Microscopic examination of the lungs showed mainly lobularly distributed pneumonia. Extensive exudation of macrophages and neutrophils was observed in the terminal respiratory tract and alveolar spaces. Warthin-Starry and Gimenez staining and electron microscopy detected many coccobacilli in the cytoplasm of exudated macrophages and neutrophils. Immunofluorescence staining using antiserum against Legionella pneumophila, serogroup 1, showed a positive reaction. Bacteriological examinations of aspirate from the respiratory tract and autopsied lung tissue confirmed the presence of Legionella pneumophila, serogroup 1. Extrapulmonary LD was not detected. LD usually affects aged or immunocompromised hosts, but there was no evidence of immune deficiency in this case. Pediatric cases of LD have rarely been reported, and a survey of the literature revealed few neonatal cases. The present case may alert neonatologists and other medical personnel to the possibility of neonatal LD infection. PMID- 1502904 TI - Kappa light chain nodular glomerulosclerosis with conspicuous crescent formation and tubulointerstitial injury. Report of a case. AB - We describe a 39-year-old man who developed kappa light chain nodular glomerulosclerosis with superimposed conspicuous crescent formation and extensive tubulointerstitial injury. The clinical picture was characterized by nephrotic syndrome and rapidly progressive glomerulonephritis. Incessantly progressive loss of renal function culminated in irreversible renal failure 7 weeks after initial manifestations of renal insufficiency. The patient has since been maintained on thrice weekly hemodialysis with chemotherapy for five years. At the time of pathologic diagnosis by renal biopsy, there was no evidence of multiple myeloma, and no serum M-component or Bence-Jones proteinuria was detected. An initial bone marrow aspirate revealed the presence of 0.6% atypical lymphocytes as the sole abnormality, although these were later identified as atypical plasma cells. These cells had also infiltrated the renal interstitium. Crescentic kappa light chain nodular glomerulosclerosis lacking evidence of plasma cell dyscrasia should be included in the differential diagnosis of rapidly progressive glomerulonephritis. PMID- 1502905 TI - Sacrococcygeal chordoma with a malignant spindle cell component. A report of two autopsy cases with a review of the literature. AB - Two autopsy cases of sacrococcygeal chordoma which showed sarcomatous components in the primary and metastatic tumors are reported. Case 1 was a 48-year-old female who died 9 years after the development of the initial symptoms. Autopsy findings showed metastatic tumors consisted of malignant tumor cells similar to fibrosarcoma and osteosarcoma. Case 2 was a 63-year-old male who died 11 years after the development of the initial symptom. At autopsy only sarcomatous tumors resembling malignant fibrous histiocytoma (MFH) were observed in the metastatic lesions. Both cases were treated with irradiation. It is suggested that the appearance of sarcomatous tumor in current two cases of chordoma might be due to the phenomenon of tumor progression closely associated with irradiation therapy. These two cases can be categorized as "chordoma with a malignant spindle cell component" in a sense that highly malignant sarcomatous components existed in conjunction with chordoma in the primary tumors. PMID- 1502906 TI - A case of pulmonary adenocarcinoma with sarcomatous elements initially manifested as a submucosal tumor of the stomach. AB - A case of pulmonary adenocarcinoma, which was initially manifested as a gastric submucosal tumor, is presented. Endoscopy showed a submucosal tumor in the fundic region in a 79-year-old Japanese woman. Initial biopsy specimens of the stomach revealed atypical spindle cell proliferation, suggesting primary leiomyosarcoma of the stomach. However, biopsy specimens obtained one year later were diagnosed as malignant lymphoma or malignant histiocytosis of the stomach. Autopsy revealed a large necrotic lesion in the right S8 region with metastases in multiple organs. Microscopy demonstrated well to moderately differentiated adenocarcinoma containing spindle or pleomorphic sarcomatous elements. Metastatic nodules including the gastric tumors all showed sarcomatous elements with no epithelial component. Immunohistochemistry showed positive reactions for keratin, epithelial membrane antigen, and carcinoembryonic antigen in areas of carcinoma, whereas most of the sarcomatous elements revealed no positivity for any of the antibodies used, except for focal keratin and EMA positivity in the primary site. This is a rare case of pulmonary adenocarcinoma with sarcomatous elements discovered as a gastric tumor at initial diagnosis, resulting from metastasis of the sarcomatous element in the submucosa. PMID- 1502907 TI - Cytogenetic characteristics of a malignant rhabdoid tumor arising from the paravertebral region. A case report. AB - The pathological and cytogenetic features of an extrarenal malignant rhabdoid tumor (MRT) arising from the paravertebral region in an infant were investigated. The patient died 4 months after diagnosis, due to aggressive tumor progression. The tumor was composed of medium-sized round cells with cytoplasm containing eosinophilic inclusions, which ultrastructurally were composed of densely packed whorled intermediate filaments. Flow-cytometric analysis of the tumor cells revealed a diploid pattern. Amplification of the N-myc oncogene was not identified. Immunohistologically, the inclusion bodies showed a positive reaction with antiserum against vimentin. The tumor cells were not reactive with antiserum against epithelial membrane antigen, anti-keratin (polyclonal) or cytokeratin (monoclonal, CK1), but did react with 5H10, an antiserum established from human sarcomatous Wilms' tumor. This case is discussed with reference to the literature on extrarenal MRT, placing stress on the histogenesis of this tumor. PMID- 1502908 TI - Alveolar soft part sarcoma. Are we approaching the goal of determining its histogenesis? PMID- 1502909 TI - Partial upper airway obstruction during sleep. Studies with the static charge sensitive bed (SCSB). AB - Nocturnal respiration, the ballistocardiogram, and body movement activity were studied with the static charge-sensitive bed (SCSB) in snorers who represented a wide range of severity of sleep-related upper airway obstruction. The emphasis was to evaluate the performance of the SCSB as a noninvasive tool for assessing nocturnal breathing disturbances. The results show that periodic episodes of obstructive apnea or hypopnea can reliably be monitored with the method. Additional breathing abnormalities suggesting the presence of increased respiratory resistance and increased body motility were frequently observed not only in OSAS patients but also in snorers without apnea. Permanent morphological abnormalities of the upper airways were observed in pharyngeal CT in patients with OSAS but also in subjects with severe partial obstruction without apnea. The findings in the SCSB recordings clearly illustrate that there is a functional continuum from partial to complete upper airway obstruction during sleep. However, the structural differences of the upper airways observed between subjects with partial airway obstruction and with OSAS suggest that partial obstruction without apnea cannot always be considered as heralding the development of the OSAS, but rather as a separate entity, which may produce the same clinical signs and symptoms as in the OSAS. The SCSB turned out to be a simple but sensitive method to detect complete and partial upper airway obstruction during sleep. The SCSB may optimally yield information beyond reach of more complex recording systems. Nonapneic SCSB findings may have particular significance for the evaluation of preclinical stages of sleep-related upper airway obstruction. PMID- 1502910 TI - Characterization of the antisecretory action of prostaglandin D2 in the rat colon. AB - Previous studies have shown that prostaglandin D2 (PGD2) inhibits neuronally mediated secretion in the rat colon. This antisecretory action of PGD2 was further characterized by the use of a prostaglandin D receptor blocker. Prostaglandin D2 inhibited the neuronally mediated short-circuit current evoked by prostaglandin I2, which represents Cl- secretion. The concentration-response curve for the inhibition by PGD2 was shifted to the right in the presence of the prostaglandin D receptor blocker, AH 6809. AH 6809 had no effect on the short circuit current response induced by prostaglandin E2 or iloprost, a stable prostaglandin I2 analogue, suggesting an interaction of the blocker with receptors specific for PGD2. A direct interaction of PGD2 with enteric neurones was studied by determining its effect on acetylcholine release from enteric neurones preloaded with [3H]choline. Prostaglandin D2 suppressed 3H release induced by electric field stimulation. It had, however, no effect on the release induced by depolarization with potassium. The results suggest that the inhibitory action of PGD2 on enteric cholinergic neurones is mediated by prostaglandin D receptors. PMID- 1502911 TI - Cardiovascular and renal effects of intracerebroventricular angiotensin II in conscious sheep. AB - Effects on systemic and pulmonary haemodynamics, renal electrolyte excretion, and plasma concentration of vasopressin, catecholamines, electrolytes and proteins in response to intracerebroventricular infusions of [Val5]-angiotensin II (ANG II) at 1, 2 and 4 pmol kg-1 min-1 in isotonic saline for 30 min were studied in conscious sheep (n = 6). Vehicle control infusions were performed in four of the animals. All three doses of ANG II were expected to increase CFS concentration of the peptide above physiological levels. All ANG II infusions were noticed to be dipsogenic, but the animals were not allowed to drink freely until at the end of the experiments (at 120 min post-infusion). The systemic arterial blood pressure increased significantly only in response to 2 and 4 pmol kg-1 min-1, concomitant with an increase of the systemic vascular resistance, whereas the cardiac output and heart rate remained unchanged. The central venous pressure increased only after administration of the highest ANG II dose, while pulmonary artery, and capillary wedge pressures were unaffected during all experiments. The plasma protein and K concentration fell in response to ANG II administration. Also here, the effects were significant only at 2 and 4 pmol kg-1 min-1. The plasma levels of vasopressin, noradrenaline, adrenaline and dopamine did not change significantly in response to any of the infusions. The renal Na excretion increased by 100-400%, but not in a strictly dose-dependent manner. Much smaller and more variable effects were seen on the renal K excretion.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1502912 TI - The importance of frequency and amount of electrical stimulation for contractile properties of denervated rat muscles. AB - Soleus (SOL) and extensor digitorum longus (EDL) muscles were denervated and directly stimulated for 23-69 days through implanted electrodes employing three different patterns. The stimulation was delivered in impulse trains where the pulse frequency differed (20, 75, and 150 Hz), while the train duration (0.3 s) and train repetition rate (1 min-1) were identical. Consequently, the number of pulses varied such that higher frequency was combined with a higher amount of stimulation. In both SOL and EDL the high-frequency pattern resulted in shorter twitch time-to-peak, greater post-tetanic potentiation, and greater tetanic force than the low frequency. Isotonic shortening velocity was increased to the same extent by all the patterns in SOL whereas in EDL fast intrinsic shortening velocity was maintained by the low-frequency pattern while it was decreased by the high-frequency pattern. We attribute this unexpected effect on the EDL to the larger number of pulses in the high-frequency pattern. By combining the present findings with previous data on directly stimulated rat muscles we conclude: in SOL the twitch duration is influenced by both the frequency and the amount of impulse activity, higher frequencies and smaller amounts leading to faster twitches. The EDL twitch duration is similarly dependent on the amount of activity, but the role of frequency is more unclear. In both SOL and EDL the isotonic shortening velocity is reduced by increasing amounts of activity and there is no evidence that impulse frequency plays a role. In EDL force output is strongly influenced by the impulse frequency, low frequencies resulting in low force outputs irrespective of the amount of activity. PMID- 1502913 TI - Pavlovian conditioning of corticotropin-releasing factor-induced increase of blood pressure and corticosterone secretion in the rat. AB - Corticotropin-releasing factor (CRF) is clearly involved in the central regulation of the pituitary-adrenal axis and, moreover, of autonomic nervous system functions. Enhanced sympathetic activity with subsequent increases in blood pressure and heart rate and attenuation of the baroreceptor reflex results from the intracerebroventricular (i.c.v.) administration of CRF. Additionally, the peptide has a variety of potent effects on behavioural responses in animals similar to those observed after an experimentally evoked stress. It was therefore of obvious interest to examine whether CRF is a possible mediator of the learning processes associated with physiological stress reaction patterns. This report clearly demonstrates a classical conditioning of the endocrine (i.e. corticosterone secretion) and haemodynamic (i.e. blood pressure) sequelae following central CRF application and thus indicates that this mechanism is of physiological significance for learned stress responses. PMID- 1502914 TI - Water intake and its thermal energy cost in reindeer fed lichen or various protein rations during winter. AB - Captive reindeer were fed four different rations which supplied equal energy but varying amount of crude protein: lichens (3%), mixed hay plus lichens (10%) and two feed concentrates with medium (12%) or high (18%) protein content. Kinetics of total body water were measured with tritiated water from February to March 1985, and thermal energy cost of daily water intake was estimated. Biological half-time of water was shorter, and daily water intake significantly higher on the hay plus lichens diet and on the medium- or high-protein concentrates diet than on the lichens diet during March 1985. Similar differences were found between reindeer on medium-protein concentrate and on lichens at the end of the corresponding feeding period during April 1986. Daily water inflow was positively correlated with a dietary supply of digestible crude protein (r = 0.916). Thermal energy costs of daily water intake were highest 1.9 MJ (3.7 l-1) in reindeer on high-protein concentrate during March 1985, and 2.0 MJ (3.9 l-1) in reindeer on medium-protein concentrate during April 1986. The reindeer fed on lichens had minimal and nearly twice as small thermal energy cost of daily water intake (mean 1.1 MJ 2.1 l-1) as on either of the concentrates. Our results show that even a moderate feed protein ration can significantly increase free water intake and its thermal energy cost in reindeer as compared to dominant natural feed (lichens) during winter. Careful protein supplementation is recommended to support body condition with a concomitant addition of easily soluble carbohydrates to compensate for increased thermal costs of water intake. PMID- 1502915 TI - Local infusion of IGF-I into the kidney of pituitary intact rats induces renal growth. AB - To determine whether insulin-like growth factor I (IGF-I) exerts growth-promoting actions on the kidneys of pituitary-intact animals IGF-I was infused into the kidney via two different routes using osmotic pumps. In a first set of experiments IGF-I was infused directly into the tissue by the use of an implanted catheter traversing the kidney. It was found that a dosage of 50 micrograms IGF-I wk-1 but not 20 micrograms wk-1 caused a gain in weight of the kidney. The growth was accompanied with morphological alterations among the cortical distal tubules. As a marker for hyperplasia, a monoclonal antibody directed against the M1 subunit of ribonucleotide reductase (RR) was used. The altered cells stained with RR, as also did the tubule cells of the medullary thick ascending limb (mTAL). No RR staining was found in the bulk of renal mass, i.e. the proximal tubules, indicating that possible growth in these cells did not involve cell division. In a second set of experiments IGF-I at 50, 100 and 300 micrograms wk-1 was infused into the renal circulation via a side branch of the renal artery, the suprarenal artery. In these experiments, no growth response or morphological alterations of the tissue were found. These findings demonstrate that IGF-I, when administered directly into the parenchyma, causes growth of the kidney in normal animals. The data are compatible with a causative role for IGF-I in the course of renal growth. PMID- 1502916 TI - Effect of increased brain serotonergic activity on endurance performance in the rat. PMID- 1502917 TI - Glycine and GABA potentiate 4-aminopyridine and/or N-methyl-D-aspartate induced [3H]-noradrenaline release from rat hippocampal slices. PMID- 1502919 TI - A comparative study of dynamic CT and ultrasonic pulsed Doppler method for estimation of the portal blood flow. AB - A new dynamic CT method for evaluating the portal blood flow is described. Thirty healthy volunteers were injected with non-ionic hypo-osmotic iodine contrast medium to estimate the portal blood flow. Time density curves (TD-curves) for the abdominal aorta and the main trunk of the portal vein were determined on the basis of data obtained by dynamic CT. From the TD-curves, portal blood flow coefficient and circulation time to flow into the portal vein (P-P time) were calculated. More detailed data of the TD-curves could be obtained by the new dynamic CT than by the previous methods. Subjects were simultaneously studied by an ultrasonic pulsed Doppler method which has been clinically accepted. There was a significant correlation between our dynamic CT method (portal blood flow coefficient) and the ultrasonic pulsed Doppler method concerning the measurement of portal blood flow. Therefore, it may be concluded that this CT method is reliable and clinically acceptable. PMID- 1502918 TI - Cepharanthin reduces thermotolerance by enhancing thermosensitivity in NIH3T3 cells. AB - The effects of cepharanthin (Ce), glycyrrhizin (G), verapamil (V), and G plus V on induced thermotolerance in NIH3T3 cells were studied. Cells were heated with or without the drug at 45 degrees C for 20 min (the first heating), incubated at 37 degrees C for 12h (the incubation period), and heated again at 45 degrees C for 0-210 min (the second heating). G and V were added throughout the experiment, while Ce was added throughout the experiment or during only the first or second heating, or the incubation period. The cells were harvested after the second heating to evaluate cell survival. In control experiments without any drug, thermotolerance developed and reached the highest peak in the cells incubated for 12h at 37 degrees C. However, thermotolerance in the control cells was suppressed by incubating them at 0 degree C, but developed by subsequent incubation at 37 degrees C. This suggests that the acquisition of thermotolerance by the cells required metabolic processes during the incubation at 37 degrees C. When each drug was present throughout the experiment, only Ce or the combined use of G and V was effective in reducing thermotolerance. Thermotolerance was also suppressed in the presence of Ce during the second heating. These results indicate that Ce reduces thermotolerance by enhancing thermosensitivity rather than by inhibiting the development of thermotolerance. PMID- 1502920 TI - Significance of urinary albumin index in the urine collected arbitrarily in the morning. AB - To evaluate urinary albumin index (UAI), the relationship between albumin excretion rate (AER) in the urine stored for 24 h and UAI in the urine collected arbitrarily on the morning of the same day was studied in 123 inpatients. The patients were admitted to our hospital from September 1, 1988 to August 31, 1989, consisting of 67 non-insulin dependent diabetics (Group 1), 40 patients with collagen disease (Group 2), and 16 patients with primary renal disease (Group 3). The relationship between log(e) AER and log(e)UAI was plotted on a graph. Pearson's rank correlation coefficients of Groups 1-3, Group 1, Group 2, and Group 3 were as follows: r = 0.725, r = 0.691, r = 0.855, and r = 0.611, respectively. The formula obtained by using Pearson's rank correlation coefficients to estimate log(e)AER from log(e)UAI in 123 cases of Groups 1-3, 67 cases of Group 1, 40 cases of Group 2, and 16 cases of Group 3 were: log(e)AER/log(e)UAI = 0.815, log(e)AER/log(e)UAI = 0.860, log(e)AER/log(e)UAI = 0.830, log(e)AER/log(e) = 0.722, respectively. In the present study, log(e)UAI was found to correlate well with log(e)AER. As AER is generally accepted to be the most reliable index to know the stage of albuminuria, UAI is considered to be clinically useful. PMID- 1502921 TI - Concentration and uptake of taurine in umbilical blood platelets. AB - The concentration and uptake of taurine in the umbilical and adult blood platelets were studied. Taurine was the most abundant free amino acid in both umbilical and adult blood platelets. The taurine concentration in umbilical blood platelets (2.30 pmoles/10(4) cells) was significantly lower than that of adult blood platelets (3.27 pmoles/10(4) cells) in contrast to the reverse relationship in taurine concentrations in umbilical and adult blood plasma. No other amino acid showed such significant difference in the concentrations between umbilical and adult blood platelets. Taurine uptake into umbilical blood platelets was temperature sensitive and sodium-dependent in a manner similar to that of adult blood platelets. The uptake conformed well to Hanes-plot. The Vmax of the uptake into adult blood platelets was about 3.6 times higher than that of umbilical blood platelets, but no significant difference was seen in the Km value between the two groups. PMID- 1502922 TI - Spa therapy improves ventilatory function in the small airways of patients with steroid-dependent intractable asthma (SDIA). AB - The improvement of ventilatory function by spa therapy was examined in 37 patients with steroid-dependent intractable asthma (SDIA) in relation to clinical asthma types. All subjects had been on long-term corticosteroid therapy before spa therapy. Spa therapy was found to improve the values of ventilatory parameters. The percent improvement in all subjects was +4.1% in %FVC, +8.9% in FEV1.0%, +9.8% in %PEFR, +22.0% in %MMF, +19.7% in %V50 and +28.2% in %V25, respectively. Relating to clinical asthma types, moderate improvement in %MMF and %V25 from 16.7% to 16.9% was observed in type Ia cases, and marked increase in %MMF, %V50 and %V25 was observed from 42.2% to 43.2% in type Ib cases. However, no significant increase was found in these parameters of types Ia or Ib after spa therapy. In patients with type II, a significant increase was shown in %V50 (p less than 0.05) and %V25 (p less than 0.01) after spa therapy. The results show that spa therapy improves the condition of small airways disorder in patients with SDIA. PMID- 1502923 TI - Influences of ventricular pacing on hemodynamics, myocardial metabolism, and cardiac work efficiency: potential risks of rate-responsive ventricular pacing. AB - The influences of ventricular pacing at a rate of 70 beats/min (bpm) on the systemic and coronary hemodynamics, myocardial metabolism, and cardiac work efficiency were evaluated in five patients with bradycardia. The results were compared to those obtained in six normal subjects at rest. In order to elucidate the effects of a relatively high rate of ventricular pacing, cardiovascular and metabolic variables were also obtained at 120 bpm in the normal subjects. It was observed that the patients eventually benefited from ventricular pacing at a rate of 70 bpm and improved in systemic hemodynamics. Although coronary hemodynamics and myocardial metabolism were accelerated, the cardiac work efficiency was not improved. A pacing rate of 120 bpm in the normal subjects did not appear to accelerate systemic hemodynamics, but adverse accelerations of coronary hemodynamics and myocardial metabolism were observed, and the cardiac work efficiency was remarkably reduced as a result. Our observations indicated that the coronary reserve capacity was very important for ventricular pacing, and suggested that an undue increment of the pacing rate not only might be meaningless but also might induce ischemic angina. Therefore, we should be cautious in using a rate-responsive pacing mode, particularly in determination of the upper limit of pacing rates, although many benefits with this pacing mode have recently been advocated. PMID- 1502924 TI - Effect of left atrial plication for the giant left atrium on left ventricular function. AB - Left atrial plication (LAP) following Kawazoe's method was performed on eight patients with mitral valve stenosis associated with a giant left atrium. To investigate the effect of LAP particularly on left ventricular function, the preoperative and postoperative left ventricular function in these patients were compared. The data were also compared to that of the non-left atrial plication (non-LAP) group with left atrial dimension of 60 mm or over. In the LAP group, there were significant differences between preoperative and postoperative data in the following parameters; New York Heart Association (NYHA) class, cardiothoracic ratio, mean pulmonary arterial pressure (PAP), left ventricular end-diastolic pressure (LVEDP), left atrial dimension, stroke volume index, ejection fraction and cardiac index. On the contrary, in the non-LAP group, there were significant differences between preoperative and post-operative data in the following two factors; NYHA class and PAP. The size of the left atrium in the non-LAP group remained unchanged over the course of long-term follow-up. Despite severe clinical symptoms and severely reduced cardiac function of the patients in the LAP group, cardiac function in all patients improved satisfactorily. This suggests that left atrial plication has a considerably beneficial effect on left ventricular function, and therefore, may be recommended for patients with a giant left atrium. PMID- 1502925 TI - Combination of epidermal growth factor and insulin is required for multicellular spheroid formation of rat hepatocytes in primary culture. AB - We showed that the combination of epidermal growth factor (EGF) and insulin is an essential supplement to Williams' #E medium for the formation of floating multicellular spheroids in primary culture of rat hepatocytes. Isolated hepatocytes assembled to form floating multicellular spheroids within 96 h through transient assembly of monolayer islands within the initial 24 h in dishes coated with liver-derived proteoglycans. However, the assembly of multicellular spheroids was severely suppressed in the absence of either EGF or insulin. The reduction of spheroid assembly was correlated with decreased attachment and subsequent decreased formation of monolayer islands within 24 h. The minimum amounts of EGF and insulin required for the formation of floating spheroids were 1 ng/ml and 0.4 microgram/ml, respectively. These results suggest that the enhancement of hepatocyte attachment provided by the combination of EGF and insulin during the early phase of culture is required for the formation of floating spheroids. PMID- 1502926 TI - Experimental study on veno-venous extracorporeal membrane oxygenation for respiratory failure after lung transplantation. AB - Extracorporeal Membrane Oxygenation (ECMO) has been adopted as a means of strong respiratory support. In lung transplantation, reimplantation response is still a serious problem. It causes severe respiratory failure which is refractory to mechanical ventilation in some cases. The purpose of this study was to evaluate the effects of veno-venous ECMO after lung transplantation using a canine autotransplantation model. The autotransplantation model was created by keeping the left lung in a warm ischemic state for 2 h. After reperfusion, the right pulmonary artery was ligated. The following two groups were studied: Group 1, Control group, (no ECMO group) (n = 6). After reperfusion, both lungs were ventilated without ECMO. Group 2, ECMO group (n = 7). After reperfusion, veno venous ECMO support was introduced with reduction of mechanical ventilation. In the no ECMO group, four of the animals died within 210 min after reperfusion. In the ECMO group, two of the animals died of severe pulmonary edema. Data of blood gas analyses (PaO2, PaCO2, and SvO2) after reperfusion were significantly better in the ECMO group, whereas there were no significant differences in both shunt fraction and pulmonary vascular resistance index. In this model with severe pulmonary edema induced by warm ischemia, veno-venous ECMO contributed to the improvement of hypoxemia and hypercapnia, but did not improve pulmonary hemodynamics. PMID- 1502927 TI - The effect of follicle-maturing drugs on mid-cycle androgen levels in women with normal baseline levels. AB - Theoretically, clomiphene citrate or human menopausal gonadotropins might have a higher chance of inducing pregnancy per cycle were it not for the concomitant rise in androgens induced by these follicle-maturing drugs. In the present study, mid-cycle androgen levels were evaluated in anovulatory women with normal baseline early follicular levels who were treated with either clomiphene citrate or human menopausal gonadotropins. The only mid-cycle androgen to rise above the normal range was androstenedione. However, no negative effects of elevated androstenedione levels on pregnancy rates were apparent. Thus, at least in women with normal baseline androgen levels, the use of follicle-maturing drugs does not appear to cause a rise in androgen levels except for androstenedione, and the rise in androstenedione at mid-cycle appears to have no adverse effect on conception. PMID- 1502928 TI - Effects of cross-gender steroid hormone treatment on prolactin concentrations in humans. AB - It is well known that peripheral prolactin levels are significantly higher in menarcheal women than in men. Higher levels of prolactin in menarcheal women are related to exposure to higher levels of estrogen in women than in men. Increased exposure to androgens in men has also been proposed as a possible reason to account for lower prolactin levels in men; however, this suggestion has not been conclusively proven. The current study sought to evaluate the cross-gender effects of male and female hormones on basal levels and the pituitary store of prolactin in humans. Four groups of individuals were involved: normal men and women, male and female transsexuals primed with female hormones and testosterone, respectively for at least 6 months. A metoclopramide challenge test was carried out on each subject of each group. Subjects were rested for 1 h, with an indwelling catheter in the antecubital vein, before a blood sample was collected for estimation of basal hormone levels. Following an oral ingestion of 10 mg of metoclopramide, blood samples were collected at 15, 30, 60, 90, 120, 150 and 180 min. Prolactin, estradiol and testosterone concentrations were measured by radioimmunoassay. Basal levels as well as metoclopramide-induced releases of prolactin (as measured by area under the curve) in normal women were significantly higher (p less than 0.05) than corresponding levels in normal men. Following long-term priming with female hormones, the pattern of response to metoclopramide in male transsexuals was dramatically changed.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1502929 TI - Vaginal bromocriptine--clinical and biochemical effects. AB - Adverse effects occur in over 50% of women taking oral bromocriptine, causing at least 10% to discontinue treatment. Although the drug is absorbed from the vagina and reportedly caused no side-effects in one patient intolerant of oral bromocriptine, long-term clinical effects of daily vaginal administration have not been assessed. We have now given bromocriptine vaginally for up to 2 years to 31 hyperprolactinemic and five normoprolactinemic women, 17 of whom were intolerant of oral bromocriptine. The drug was well absorbed from the vagina and a daily dosage of 2.5 mg lowered serum prolactin levels in 28 of the hyperprolactinemic women (in 11 to within normal limits), restored menstrual cyclicity, and abolished galactorrhea; one of the four infertile women conceived. Minor side-effects occurred in only three women. Vaginal administration is clinically effective, avoids the adverse effects of oral therapy and could be the first-line treatment for patients requiring bromocriptine. PMID- 1502930 TI - The frequency of salivary progesterone sampling and the diagnosis of luteal phase insufficiency. AB - A profile of salivary progesterone concentrations, based on daily samples taken over a full menstrual cycle, provides a detailed picture of changes in luteal function, at the expense of analyzing a large number of samples. Strain can be placed on analytical services by assaying daily samples instead of one or a few serum (or saliva) samples. This study sought to determine the minimum number of salivary progesterone determinations which adequately describe luteal function. Daily salivary progesterone levels from 215 cycles, of which 29 cycles had progesterone profiles indicative of luteal phase insufficiency, were analyzed to ascertain the efficiencies of various sampling patterns of reduced frequency. A single mid-luteal salivary progesterone estimation or the mid-luteal Lenton progesterone index (n = 4) satisfactorily reflected the normal luteal phase, but a frequency of one sample every 3 days over the luteal phase (n = 5-6) was necessary to allow recognition of a short luteal phase or poor progesterone surge. PMID- 1502931 TI - Comparison of ovarian response in the same women with the same or different lots of human menopausal gonadotropin. AB - A variation in the bioactivity of different production lots of human menopausal gonadotropin (hMG) has been suggested. Therefore, we evaluated ovarian response to hMG in 14 women during three separate IVF cycles. The first two cycles were performed with the same lot (#03310027; Cycles A1 and A2); the third cycle utilized different lots of hMG (Cycle B). In all cycles, hMG was administered 3 ampules/day beginning cycle Day 3 and continued for at least 6 days. Estradiol and ultrasound evaluations were performed on Day 3, and then daily, beginning on cycle Day 8. Fourteen women completed all three cycles. There were no significant differences in baseline estradiol and ultrasound. Estradiol levels on Day 8 (A1, 754 +/- 130; A2, 700 +/- 107; B, 520 +/- 80 pg/ml, analysis of variance p greater than 0.5) and on Day 9 (A1, 1051 +/- 144; A2, 1140 +/- 155; B, 840 +/- 124 pg/ml, p greater than 0.05) were similar as well. The number of small (1.0-1.4 cm) follicles, large (greater than or equal to 1.5 cm) follicles, and total follicles (Day 8: total A1, 5.5 +/- 0.9; A2, 4.0 +/- 0.7; B, 4.5 +/- 0.9, p greater than 0.05; Day 9: total A1, 6.7 +/- 0.9; A2, 6.9 +/- 0.8; B, 6.9 +/- 0.9, p greater than 0.05) in all three cycles were also similar.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1502932 TI - Postmenopausal osteoporosis: prevention and treatment with calcitonin. PMID- 1502933 TI - Steroidogenesis in vitro of human granulosa-luteal cells pretreated in vivo with two gonadotropin releasing hormone analogs employing different protocols. AB - We have previously observed impaired progesterone accumulation in vitro in response to human chorionic gonadotropin (hCG) by cells pretreated in vivo with a gonadotropin releasing hormone analog (GnRH-a). The present study was conducted in order to evaluate different protocols for GnRH-a in in vitro fertilization (IVF), employing two different available analogs. Granulosa-luteal cells were collected at ovum pick-up and stimulated with hCG. Buserelin (Bus) was employed as long (Bus-L) and short (Bus-S) protocol, and Leuprolide (Leu) was also used as long (Leu-L) and short (Leu-S) protocol. Progesterone accumulation in vitro was compared with cells treated with clomiphene citrate (CC) and gonadotropins. Maximal progesterone production was observed on culture day 6 using Bus-L in comparison to day 4 when clomiphene citrate was employed. While Leu-S showed a similar pattern of progesterone accumulation to clomiphene citrate, Leu-L and Bus S had an intermediate pattern. The response to hCG was maximal on day 4 for the clomiphene citrate- and Leu-S-treated cells, while the rest of the protocols had a peak on day 6. In addition, hCG consistently stimulated progesterone production in all protocols except in Bus-L. These results confirm an altered progesterone accumulation in vitro when GnRH-a are used. The effect seems to be more evident in long protocols, especially when buserelin is used, suggesting a higher accumulation of the analog in follicular fluid. PMID- 1502934 TI - [Coexistence of hepatic and pancreatic disease in the chronic alcoholic. Unusual or frequent situation?]. AB - In all that has been written there is still some controversy about the importance of the simultaneous pathologycal involvement (functional and/or morphologic) of the pancreas and liver on the same alcoholic patient. Thus, and with the intention of reaching an agreement on the matter, we studied on one hand, on a functional basis, the exocrine pancreas in a group of alcoholic cirrhotics (n = 75) and, on the other, we analysed on a triple perspective--clinical, biological and anatomic-pathological--the pathological involvement of the liver in a series of cases (n = 20) with chronic calcifying pancreatitis. In such case, we verified that, essentially, the secretory capacity of the pancreas had diminished in 17.3% of the cirrhotic cases, while on the other hand, the clinical-laboratorial and anatomic-pathological analysis of liver on pancreatic patients showed clinical biological suspicion of alcoholic hepatic disease, serious lesions considered pre cirrhotic and established cirrhosis, respectively in 56.2%, 12.5% and 6.2% of the cases. We conclude that, although the idea of rarity in associating hepatic cirrhosis with chronic pancreatitis, came through on the clinical symptomatological observation plan, certain investigations of functional and/or histopathological nature, run by us on alcoholic patients, proved to suffer from these affections, permitted us to indicate that the coexistence of pathological involvement of these two organs should not be underestimated. PMID- 1502935 TI - [Risk or pre-term labor. A cross-sectional study of its determinant factors]. AB - Substancial evidence links gestational duration to birth outcome, and a large number of determinants for premature delivery have been identified. However, most preterm births (gestational age of less than 37 weeks) remain unexplained, and there is a wide geographical variation in risk factors. The purpose of this epidemiologic survey was to study the relationship between gestational duration and the mother's demographic, obstetric and nutritional characteristics, clinical course of pregnancy and labour, alcohol, coffee and tobacco consumption, and prenatal care. Data were collected for 740 consecutive deliveries (3.6% preterm) corresponding to 750 live-births. Except for the number of prenatal visits, no relation was found between gestational age and the variables assessed (r approximately equal to 0). There was an increased risk for preterm delivery when a disease complicated the course of pregnancy (OR = 2.7), there were less than 6 prenatal visits (OR = 4.9), pelvic presentation (OR = 5.7) or twins (OR = 12.7). After adjustment for these variables only prenatal care and twinning remained significantly associated with an increased risk. In this population, the authors identified prenatal care as the most important modifiable factor associated with preterm delivery. PMID- 1502936 TI - [Tetanus. A review of 54 cases]. AB - Tetanus continues to be a frequent illness with a high rate of mortality which mainly affects the elderly. In view of this, 54 cases treated in the ICU between 1983 and 1991 were studied. The clinical support with mechanical ventilation and the use of new drugs, which allowed for a more satisfactory sedation and muscular relaxation, and which permitted the control of the autonomic overactivity, were the most determinant factors in the reduction of mortality verified in the late years of our practice. PMID- 1502937 TI - [Culture diseases. Brief review on the way characteristics of today's life affect the ways of mental disease]. AB - Culture is expressed in the content of psychiatric symptoms. In this paper we try to establish a relationship between the pathoplasticity of some paradigmatic psychiatric disorders and characteristics of values and life styles in developed societies. We argue that some aspects of a marked hedonism hide a dangerous nihilism and they both articulate, in a discrepant way, with opposing responsible hiperrational and hypercompetitive register. Doctrinaire fanaticisms increase markedly in other places in the globe with endemic shortages while solid values lack in the societies of abundance. This affects mental health. PMID- 1502938 TI - [Changes in cardiac output in the initial phases of hypertension]. AB - In what concerns to the early phases of arterial hypertension, the difficulty of definition, the usually found hemodynamic changes, especially of cardiac output, and its changes during evolution to established hypertension, are referred. The role of genetic determinants of predisposition to hypertension and of strain situations as factors of precipitation, with acute rise of blood pressure and cardiac output, is emphasized. It is also referred the importance of the early detection of true hypertensives by studying their reaction to strain situations, being particularly promising the mental stress tests and the dynamic exercise tests. PMID- 1502939 TI - [Central and peripheral vascular resistance]. AB - Better knowledge of organ damage produced by arterial hypertension in multiple conditions led to the conclusion that blood pressure readings (the values) were not the only determinant but instead a whole range of factors dependent on the arterial wall characteristics. The concept of windkessel in relation to the stiffness and the compliance of the arterial system, the impedance at any given point evoking different volume/pressure/flow relationship (with pressure tracings) rekindled interest in this matter, leading to a more adjusted model. Invasive (micromanometers) and non-invasive methods (such as the echodoppler) are the investigation and clinical support of this new interest in an old idea developed before the epidemiological period of arterial hypertension study. The similitude between ageing and hypertension, the contraposition that is seen in youngsters, and other metabolic alterations test this model of winkessel. PMID- 1502940 TI - [Renal dysplasia: clinico-pathologic review]. AB - Histology records from 63 nephrectomies were reviewed; 22 patients had unilateral totally dysplastic kidneys and 5 had polar or segmental dysplasia. A clinicopathological study of these cases was undertaken. In the first group, there was a slight male preponderance and 75% of the patients presented were under two years of age. Urinary tract infection was the most common complaint. 4 patients were diagnosed in utero by ultrasound and 5 infants presented an abdominal mass. Hypertension was documented in a newborn baby. Ipsilateral lower urinary tract anomalies were found in 12 patients and those of the contralateral kidney in 2 children. There were 3 cases of extrarenal anomalies. Histological examination revealed 13 cases of multicystic dysplasia and 9 of solid dysplasia. Metaplastic cartilage was found in 1 case. In the group of segmental dysplasia, age ranging from 27 weeks' gestation to 8 years, at the time of the diagnosis. They all had duplex kidneys and 4 had ureterocele. Histological study in these cases was similar to the one found in the previous series, although superimposed inflammatory changes were more pronounced. Some of the theories regarding the pathogenesis of this disorder are reviewed and the importance of its diagnosis is emphasised. PMID- 1502941 TI - [Psychosomatic research in ischemic cardiopathy]. AB - The need felt in the last decades for research concerning the psychosocial aspects of Ischaemic Heart Disease is emphasized. Different methodologies of research in this area are described, as well as their usefulness in different kinds of studies. The main areas of research in Ischaemic Heart Disease and the more recent advances in some of them are mentioned. Finally, the most promising fields for future research in Ischaemic Heart Disease are emphasized. PMID- 1502942 TI - [Benign pleural effusion caused by asbestos exposure]. AB - The Authors present the first case described among us of benign pleural effusion of an asbestotic origin. They stress the importance of thoracoscopy (pleuroscopy) in the diagnosis of this situation. Attention is drawn to the fact that asbestotic lesions and asbestotic bodies have been found in the lung and, in particular, in the parietal pleura as well. They emphasize the fact that exposure to asbestos was not realized by the patient, which made the clarification of the situation more difficult. It was a CT scan that showed the signs suggestive of exposure to asbestos which raised the diagnostic suspicion. They conclude that every patient with a pleural effusion must be thoroughly questioned about exposure to asbestos. Even if the exposure is accepted, they consider that one should proceed to a pleuro-pulmonar biopsy by thoracoscopy. This biopsy allows demonstration of the characteristic histopathological lesions and rule out other etiologies, namely malignancy and tuberculosis. They suggest that these patients must be highly motivated to stop any smoking and kept under periodic surveillance. PMID- 1502943 TI - [Diffuse hyperplasia of the thymus after chemotherapy for Hodgkin's disease]. PMID- 1502944 TI - Management of giant intracranial aneurysms. AB - Based on an own material of 64 cases a survey is given on the management of giant intracranial aneurysms. Essential investigations are as well CT and Magnetic Resonance Scanning as detailed angiographic studies. With regard to the operative handling the following questions are discussed: approach; use of temporary vascular occlusion and related monitoring; preparation of the aneurysm neck for occlusion. In cases without recent subarachnoid haemorrhage morbidity and mortality were less than 10%. It was 15% in cases where recent haemorrhage had occurred. PMID- 1502945 TI - Arteriovenous malformations of the posterior fossa. AB - AVMs of the posterior fossa are reviewed on the basis of personal experience of 47 cases including 2 venous angiomas, 7 cavernous angiomas, 5 arteriovenous fistulas and 33 true arteriovenous malformations and of the few series reported in the literature. MRI is now an indispensable tool to define the exact localization of any malformation. Combined with angiography, it permits one to choose the most adequate therapeutic strategy and the best surgical approach. Radical cure is to be contemplated in most cases considering the often dramatic consequences of bleeding at the infratentorial level. Deep AVMs and moreover cavernous angiomas, even those located in highly functional structures such as the brain stem, can now be discussed for treatment. Encouraging results have already been obtained using, alone or in association, the recently advanced modalities of treatment: interventional neuroradiology, radiosurgery, and microsurgery. PMID- 1502946 TI - Surgery of tumours of the lateral ventricle. AB - Tumours of the lateral ventricle in most cases enlarge significantly before signs and symptoms are exhibited. In the years between 1980 and 1991 we encountered 55 patients of all age groups with tumours of the lateral ventricle. All were diagnosed either by CT or MRI, and in lesions with good enhancement on CT additional angiography was performed. All 55 tumours were operated upon using microsurgical techniques. The approach was chosen according to the location of the tumour, preferably transcortical. In selected cases large tumours were removed in a two-stage operation. Only in one frontal horn and Cella media tumour an interhemispheric transcallosal approach was used. Postoperative or surgically related mortality was experienced in 3 cases. Life expectancy and morbidity were dependent upon histology. PMID- 1502947 TI - Treatment of tumours of the pineal region and posterior part of the third ventricle. AB - The evaluation of tumours located in the posterior part of the third ventricle or pineal region is achieved best by magnet resonance imaging (MRI). It shows the exact localization and extent, the involvement of neighbouring structures like thalamus or quadrigeminal plate and the displacement of the large veins, the internal cerebral veins, the vein of Galen and the veins of Rosenthal. If only CT is available, angiography should be performed prior to operation to identify the course of the veins. In children with a pineal region tumour the "tumour markers" AFP and beta-HCG should be determined before operation. We approach the rare tumours entirely located within the posterior part of the third ventricle by the posterior interhemispheric transcallosal route with the patient in prone position with the head elevated. The same approach is used for pineal region tumours extending above the internal cerebral veins. Tumours arising from the posterior thalamus extending into the thalamus and ventricle as well, are better approached by the posterior transcortical transventricular route since the lateral view is rather limited by the midline approach. The most frequent tumours in the pineal region are approached if they are located below the internal veins by the infratentorial, supracerebellar route in the sitting position. A total of 60 cases are evaluated. If AFP and/or beta-HCG are positive a highly malignant nongerminomatous germ-cell tumour must be suspected. We recommend initial chemotherapy with a combination of Vinblastine, Ifosfamide and Cis-platin without biopsy to avoid tumour seeding. After the "markers" are normalized operative removal of the residual tumour and radiotherapy should be carried out. In a series of 13 children operated on for pineal region tumours a rigid neuropsychological and endocrine evaluation was performed with encouraging results. During the last 10 years we have performed 49 open operations and 11 stereotactic biopsies. 40% of the patients were children under the age of 18. 40% of the tumours in childhood and 60% in adults were benign. In childhood 24% were germinomas and 20% non-germinomatous germ cell tumours. PMID- 1502948 TI - Tumours of the limbic and paralimbic system. AB - 240 patients with tumours of the limbic and paralimbic areas are presented. The following tumour growth patterns have been observed: they remain isolated to areas within the allocortex; they spread throughout allocortical regions; they spread from allocortical to mesocortical zones. With the exception of advanced malignant tumours there seems to be a tendency for tumours to spare the adjacent neocortical and medial structures. The tumours can be approached and extirpated using the trans-Sylvian approach and microneurosurgical technique. 56% have been histologically benign. 60% were below 40 years of age. Seizures were the leading manifestation (77%). In 95% the postoperative results were good. There was no peri-operative mortality. PMID- 1502949 TI - Open stereotactic selective amygdalo-hippocampectomy for drug resistant epilepsy. AB - Selective removal of the medio-basal temporal structures has been introduced as an alternative to standard temporal lobectomy in the treatment of intractable temporal lobe epilepsy not related to gross structural lesions. Various approaches have been described for the surgical excision of the amygdalo hippocampal complex, each of them presenting advantages and limitations. The recently introduced computer-assisted technique of volumetric stereotactic excision of deep-seated intracerebral lesions combines precision of targeting with elimination of unnecessary cortical trauma and may potentially provide an alternative method in the treatment of temporal lobe epilepsy. We present our experience of stereotactic volumetric selective amygdalo-hippocampectomy in six patients with medically intractable temporal lobe epilepsy. The criteria for selection, the pre-operative evaluation and the operative technique are discussed. All patients had a cessation or considerable reduction in seizure frequency while the morbidity was minimal. PMID- 1502950 TI - Surgery of hydrocephalus: past, present and future. AB - The treatment of hydrocephalus, over the centuries, underwent three stages of evolution. During antiquity, middle ages and Renaissance, hydrocephalus was not understood. Medical treatment was useless; surgery was hopeless. The second stage extends from the XIXth century to the end of the first half of the XXth century. CSF circulation was now understood; surgery however, remained inefficient, but some patients survived with arrested hydrocephalus. The third stage begins in the nineteen fifties with the development of silicone shunts with a valve. Surgery transforms the prognosis of hydrocephalus, but the number of post-operative complications creates new problems. The different attempts that have been made during these past two decades to solve these problems are reviewed. They have resulted in a reduction of the mechanical and infectious complications. CSF overdrainage has been minimized. Percutaneous ventriculo-cisternostomies have in some cases replaced shunts. In the future, to improve outcome in these hydrocephalics, surgery, when indicated, should be performed as early as possible. Knowledge and prevention of the causes of hydrocephalus should be developed. PMID- 1502951 TI - Early prediction of outcome in severe head injury. AB - A survey is given of the development and actual state of the prediction of outcome in severe head injury. Thanks to the data collection in some large databanks it has become possible, in a relatively large number of cases, to estimate reliably the chances of survival and the chance of developing an intracranial haematoma base on clinical data and CT obtained during the first 24 hours. Later during the posttraumatic course prediction is possible of the degree of remaining disability in survivors, and the chances of developing epilepsy and neuro-behavioural sequelae. Due to changing management-regimens further data collection in international databanks is necessary. PMID- 1502953 TI - Indications for neurosurgical treatment of chronic pain. AB - Guidelines are presented for the neurosurgical treatment of chronic pain. In these guidelines a distinction is made between the pain of cancer and neurogenic pain. In cancer pain the survival time and the location of the lesion are the important guidelines. Possible procedures are: opioids via CSF route, lesions in nociceptive pathways and PV-PAG stimulation of the thalamus. In neurogenic pain, neurostimulation procedures, tailored to the location of the pain are procedures of first choice. There are however specific indications for other procedures depending on the aetiology of the pain. Causalgia and reflex sympathetic dystrophy: sympathetic blockade; Tic douloureux: radio-frequency lesion, glycerol, balloon inflation of the ganglion of Gasser, and microvascular decompression; Plexus avulsion: dorsal root entry zone lesion (D.R.E.Z.). There is a need for controlled prospective neurosurgical trials in which as a minimal rule an independent party should evaluate the results of the surgical procedure. PMID- 1502952 TI - Image directed stereotactic surgery for brain stem lesions. AB - Advances in neurological imaging may have increased the diagnostic accuracy and the detection rate of intrinsic brain stem lesions, but a histological diagnosis is still an essential requirement for rational and appropriate management. Open exploration allows biopsy and resection in cases where an exophytic component is present. The surgical inaccessibility and the resultant morbidity of these approaches, however, associated with a low diagnostic yield in cases with no visible surface abnormality, are important limiting factors. A series of 45 brain stem lesions stereotactically approached with CT or MRI guidance is presented. A transcortical frontal pre-coronal trajectory was used in all of them. Haematoma was preoperatively diagnosed in 10 cases and the procedure was for therapeutic aspiration. Of 35 cases where the diagnosis was uncertain, although intrinsic tumour was suspected, positive results were obtained in 33, while unexpected findings of granuloma, lymphoma, angioma, leucoencephalopathy, vasculitis and radiation necrosis were found in over 10% of the cases. There were no operative deaths and the morbidity was low. In no case was there a permanent neurological deterioration directly related to the procedure, although there was a transient deterioration in two patients and one patient required early reaspiration of a haematoma. Image directed stereotactic approaches to brain stem lesions can combine a high degree of accuracy (offering positive histological diagnoses) with a low operative morbidity. MRI directed biopsies can complement CT guided ones thus increasing the number of suitable cases and improving the success rate. The frontal precoronal transcortical trajectory provides safe access to the majority of the brain stem targets. PMID- 1502954 TI - Surgery of intramedullary spinal cord tumours. AB - MRI and Cusa have significantly modified the diagnosis and the treatment of intramedullary tumours. Our experience, based on 66 cases, is in favour of surgery performed when the patient's neurological status is still good. Radical surgery, whenever possible, is the best treatment and can be achieved for many histological diagnoses, even in gliomas where we succeeded in 36% of the cases. Surgery is the only way to be sure of the exact histological diagnosis of the lesion which can be suggested in 70% of the cases but not confirmed by MRI. PMID- 1502955 TI - Infections of the spine. PMID- 1502956 TI - Ethics in neurosurgery. PMID- 1502957 TI - The future of neurosurgery. AB - Many factors influence the future of neurosurgery, among them the general growth of the world population with an increasing number of older persons and the political-economical development which differs markedly from region to region. Another important factor will be the biological and molecular revolution which has just begun and makes it likely, that some of the pathologies, which needed neurosurgical management, become accessible to conservative treatment in the future. Finally the neurosurgical sphere of activity is endangered by take-over tendencies of neighbouring medical specialties. Those of us who are in charge of neurosurgical organization and planning should take these and additional factors into consideration early enough, in order to give neurosurgery and neurosurgeons a chance to adapt to the future. PMID- 1502958 TI - Neurosurgical publications in European journals. AB - The number of papers published in European neurosurgical journals during the last decade (1980-90) was analysed using online databases. Thirteen journals devoted to neurosurgery were published in Europe at that time. In five of them neurosurgery appears together with other specialties. Almost 50% of all European neurosurgical journals are written in English. They published 68% of all papers by neurosurgeons appearing in the European neurosurgical journals during the last decade. Together with the American neurosurgical journals English was used in about 80% of all neurosurgical publications. Other languages used are German and French (9% each), Russian (5%), Czech or Slovak (4%), Polish (3%), Rumanian (2%). Most papers by European neurosurgeons originate from England, followed by Germany, France, Italy and Sweden. Of the East-European countries Polish neurosurgeons contributed with 782 publications, followed by Czechoslovakia (568), Hungary (501), USSR (470) and East Germany (452). The proportion of papers published in neurosurgical journals by European neurosurgeons to those in the journals devoted to other neurosciences varied from 99% in the USSR to 12% in Austria with an average of 38%. Citation analysis indicates that only a few of the journals have a large impact on neurosurgical publications, while the others have a rather limited influence. PMID- 1502959 TI - [Annual treated psychopathological morbidity. Demographic and diagnostic features]. AB - We report in this study the demographic and diagnostic variables of all successive outpatients, age 16 years and older, treated during a one year time period, at a Psychiatric Unit of the Spanish Seguridad Social. Diagnosis were made following DSM-III Criteria. Epidemiologic parameters calculated were population based treated morbidity rates. The total number of patients seen was 1,119, annual rate of 13.16 per 1,000 population. Females outnumbered males significantly (rates of 18.25 and 8.41, respectively). Annual rates are compared with six months previously obtained rates. In general, a consistent sex/age epidemiologic profile was found for most DSM-III diagnostic categories. Implications for planning Mental Health Care Systems, as well as for evaluating Epidemiologic Field Surveys in Psychiatry, all of potential value, can be derived from the data. PMID- 1502960 TI - [Carbamazepine: an efficient adjuvant treatment in schizophrenia]. AB - Different studies published in the last years have focused on the psychotropic effects of carbamazepine (CBZ). This study tries to investigate the efficacity of CBZ as an adjunct treatment of schizophrenia. 20 patients with a diagnosis of paranoid schizophrenia, according to the RDC, have been investigated by double blind method. Subjects are divided in two groups (n = 10). The first one is treated with CBZ (with dose in order to reach a plasma level between 8-12 mg /l) and Haloperidol (oral fixed dose: 30 mg /day). The second group only with Haloperidol (same dose). Clinic and psychopathological disturbances are evaluated with the BPRS, and secondary effects with the UKU scale. A clinical improvement (90%, measured by the BPRS) was observed for both groups, without significant differences. Patients treated with CBZ show an important reduction of neurological secondary effects related to neuroleptics (Haloperidol). Carbamazepine appears to be a useful treatment, combined with neuroleptics, for acute schizophrenic episodes. PMID- 1502961 TI - [Buprenorphine use, a bad prognostic indicator in drug dependence]. AB - We studied 184 patients with DSM III-R diagnostic criteria for opiate dependence and classified them in order of their buprenorphine use: those who never used it (21%), others who used it from time to time (43.5%), and those who use it habitually (35.5%). The patients who use buprenorphine habitually have a poorer social functioning and are more disturbed clinically. They present too: more unemployment (p less than 0.05), longer time of opioid dependence (p less than 0.05), they offend usually (p less than 0.001), they traffic in drugs more than the other patients (p less than 0.001), mostly buprenorphine (p less than 0.001) and they are usually polydrug-addicts (p less than 0.001). PMID- 1502962 TI - [Psychiatric diseases in the elderly in an urban Aragonese population (Spain) and their relation to health determinants]. AB - As a part of the SAMAR 89 Project on mental health, we present the results of a psychiatric epidemiological research (in two stages) in a representative sample of the elderly urban population of Zaragoza (Spain). We study the relation between psychological disorders and sociodemographic factors, and network and social support. In the first stage we use a adaptation of the Enquete Sante Quebec and the General Health Questionnaire of 28 items of Goldberg. The Clinical Interview Schedule and the monumental state of Folstein were used for the psychiatric diagnoses in the second stage (diagnoses criteria of the DSM-III). The psychological disorders were more frequent on the women, the more aged and the ones of low socioeconomic level. Also was detected a correspondence between bad mental health and problems in the network and social support. PMID- 1502963 TI - [Comparison of the attitudes of Brazilian and Spanish medical students towards mental disease]. AB - The purpose of this study was to compare the attitudes towards mental illness held by Brazilian and Spanish medical students. These attitudes were measured by means of the Opinions about Mental Illness Scale (OMI), developed by Cohen and Struening in 1962 in the United States, and translated and adapted by Rodrigues in 1983. The scale was answered by 214 5th year students of the School of Medicine of Ribeirao Preto, Brazil (61), and of the School of Medicine of Salamanca, Spain (147), and the data were analysed through the transformation of the raw scores to seten scores. From the seven attitudinal dimensions yielded by the adapted OMI, the subjects showed significant differences in relation to the attitudes called Benevolence, Social Restrictiveness and Mental Effort Etiology. Other significant differences were also found when mean scores were grouped by respondents' sex and future medical specialization. PMID- 1502964 TI - Improvement in pulmonary function following smoking cessation. AB - This study investigated improvement in pulmonary function following smoking cessation. It employed three indices of lung function that are sensitive to improvement following smoking cessation and that can be easily assessed within a clinical setting: maximum mid-expiratory flow (MMF), forced expiratory volume in 1 second (FEV1), and forced vital capacity (FVC). Smoking status was verified by saliva thiocyanate analysis. Significant improvement in MMF was evident after 3 months of cessation and was maintained at the 6-month follow-up. This study demonstrates that significant improvement in at least one parameter of lung function occurs within the time span typically used in smoking cessation programs. PMID- 1502965 TI - Using knowledge maps and scripted cooperation to inform college students about patterns of behavior related to recurring abuse of alcohol. AB - Objectives of this study were to determine the effectiveness of using a specific information format--graphic representations called knowledge maps--and an information processing strategy--scripted cooperation--in teaching college students about behavior patterns that underlie recurring abuse of alcohol. Participants in this three-session, 6-hour study were 111 Texas Christian University students recruited from undergraduate psychology classes. Participants were randomly assigned to one of two materials format conditions (map vs. text format) and to one of two processing strategy conditions (individual processing vs. scripted interaction with a partner). Results indicate that map format facilitated recall of the pattern information; processing with a partner appeared to enhance perception of the multidimensional nature of behavior that supports alcohol use. PMID- 1502966 TI - The abstinence violation effect and very low calorie diet success. AB - This study evaluated the relationship between Marlatt and Gordon's (1985) Abstinence Violation Effect (AVE) and fasting outcomes of patients enrolled in a Very Low Calorie Diet (VLCD) and behavior education program. Within the first 11 weeks of the VLCD, 41 of 76 patients reported a fasting lapse and rated this lapse on an attribution scale. Patients reporting greater characterological attributions for their first lapse (i.e., a higher AVE) lost a smaller percentage of their excess weight during active fasting than patients reporting more situational attributions r(39) = -.36, p less than .025. First lapse AVE ratings did not distinguish between program dropout versus completer status, but high AVE dropouts did spend fewer weeks in the VLCD program than low AVE dropouts, r(12) = -.54, p less than .05. Although a faster's initial level of obesity accounted for the largest portion of weight loss outcome variance, the AVE accounted for a significant additional portion of outcome. PMID- 1502967 TI - A time series investigation of three nicotine regulation models. AB - Time series data were collected twice daily for 62 days from 10 individuals on three variables related to smoking habit strength: number of cigarettes smoked, salivary cotinine, and carbon monoxide. The two purposes of this study were: (a) to evaluate which time series model(s) best fits each of the measures; and (b) to determine which model of nicotine regulation is consistent with the data. Three models of nicotine regulation were considered: (a) nicotine fixed effect; (b) nicotine regulation; and (c) multiple regulation. These models provide different predictions about the size and direction of the lag-one autocorrelation. Each measure was described in terms of one of a family of time series models represented mathematically as ARIMA (p, d, q). Models varied by individual, but a single model described the majority of subjects for all three variables. The clearest model identification was for the number of cigarettes smoked where an ARIMA (1, 0, 0) model with a moderate to strong negative dependency fit the majority of the subjects. This provided strong support for the multiple regulation model. An appendix provides a brief review of time series methodology. PMID- 1502968 TI - Adequacy of recall of drinking patterns and event occurrences associated with natural recovery from alcohol problems. AB - The adequacy of recall of drinking and events surrounding natural recovery from alcohol problems was investigated with 21 abstinent and 18 active untreated problem drinkers. During structured interviews, drinking was assessed for 6 years, and events were assessed for 1 year; both assessment periods ended about 6 years before data collection, which corresponded with the beginning of sobriety for abstinent subjects. The accuracy of subject reports of both variable classes was evaluated through comparisons with collateral reports, and the reliability of drinking reports was evaluated by reinterviewing a subset of subjects about 2 months after the first assessment. Reliability was generally high for subjects' drinking reports. Subject-collateral agreements were significant for drinking and event variables that collaterals could readily observe, but not for variables that were less observable. Current drinking status and the length of recall did not influence reporting accuracy. With some qualifications, these findings support the use of structured recall procedures to investigate drinking patterns and environmental circumstances related to natural recovery and highlight limitations in the use of collaterals as a verification method. PMID- 1502969 TI - Relationship of diagnostic, demographic, and personality variables to self reported stimuli for chemical use. AB - While extensive research has been conducted to determine internal and external stimuli for drinking by alcoholics, the topic of how demographic, diagnostic, and personality variables may relate to these precipitants is largely unexplored. This study suggests that stimuli to use alcohol or drugs differ partly as a function of diagnosis (alcohol dependence vs. concurrent alcohol and drug dependence). Age, education, and gender do not appear related to the stimuli in either diagnostic group. Personality characteristics of cognitive reflectiveness, impulse control, sociability, and intrapunitiveness, however, seem to be associated with certain classes of high risk stimuli. PMID- 1502970 TI - Predictors of smoking relapse among self-quitters: a report from the Normative Aging Study. AB - We followed 235 adults for one year after a self-initiated attempt to stop smoking cigarettes. Relapse rates were much larger than expected in the early days and weeks after the quit attempt. Approximately 62% had relapsed by 2 weeks after their quit dates. Those who smoked any cigarettes at all in the post cessation period (i.e., lapsed) had a 95% probability of resuming their regular pattern of smoking subsequently. Shorter periods of abstinence on prior quit attempts, greater pre-cessation consumption of alcoholic beverages, and lower pre cessation levels of confidence in quitting were related to relapse. In addition, abstainers who reported decreased confidence after cessation concerning their ability to maintain abstinence were more likely to relapse thereafter. The presence of a greater proportion of smokers in the subjects' environment also increased the likelihood of relapse. Demographic variables such as age, gender, and education level did not predict relapse. Likewise, neither baseline psychosocial stress levels, nor post-cessation increases in stress were related prospectively to relapse. Clinical implications of finding are discussed. PMID- 1502971 TI - Co-occurrence of substance abuse with conduct, anxiety, and depression disorders in juvenile delinquents. AB - The purpose of the current study was to examine the co-occurrence of substance abuse and three other psychiatric disorders (conduct disorder, depression, anxiety) in an incarcerated juvenile delinquent sample. Diagnostic interviews were utilized to place participants in one of three groups: No substance abuse, alcohol/marijuana abuse, or polysubstance abuse. Frequency of diagnosis and number of symptoms of three psychiatric disorders were then examined. The results indicated that the diagnosis of conduct disorder increased significantly with the occurrence of substance abuse. Also, the number of symptoms for conduct disorder, anxiety, and depression increased with substance abuse. With polysubstance abuse the probability of having more than one of the other psychiatric diagnoses was above 50%. Potential explanations for the findings, focusing on the developmental trajectory for conduct problems and self-medication for internalizing disorders, are discussed. PMID- 1502972 TI - The impact of prior substance abuse on treatment outcome for bulimia nervosa. AB - The present investigation examined the significance of a past history of substance abuse on treatment outcome for bulimia nervosa. Seventy-five women with bulimia nervosa participated in a 6-week double-blind outpatient trial of desipramine; 19 patients had a history of substance abuse and 56 did not. Although patients with a history of substance abuse reported higher levels of anxiety and depression at presentation for treatment than patients without such histories, the two groups reported a similar age of onset of their bulimia nervosa and similar severity of eating pathology with regards to binge and vomit frequencies and measures of concern about body shape and weight. On all outcome measures, the improvement of the substance abuse group was equal to or greater than that in the group without a history of substance abuse. Results suggest that a past history of substance abuse has no implication regarding response to pharmacological treatment for bulimia nervosa. PMID- 1502973 TI - Relationships among borderline features, body dissatisfaction and bulimic symptoms in nonclinical females. AB - The present study evaluated the utility of combining measures of body dissatisfaction and borderline personality features in screening high-school girls who may be at risk for bulimia nervosa. Two samples (777 high-school girls and 22 bulimic women in-treatment) completed scales assessing borderline traits, body dissatisfaction, eating symptoms, and associated psychiatric disturbances. Students were divided into four groups, respectively showing: (a) high body dissatisfaction and borderline traits, (b) high body dissatisfaction alone, (c) high borderline traits alone, or (d) neither vulnerability component. Clinical and nonclinical groups were then compared for severity of eating and psychiatric symptoms. Girls displaying the combination of high body dissatisfaction and borderline traits (our presumed "high-risk" group) showed an elevated profile of eating and associated disturbances, highly comparable to the bulimic group. They were also more likely to receive threshold and subthreshold diagnoses of bulimia nervosa (according to simulated diagnoses based on self-report items) than subjects in other high-school groups. Implications of these findings were discussed with reference to the "two-component" model of eating disorders. PMID- 1502974 TI - Human antibody effector function. PMID- 1502975 TI - Role of perforin in lymphocyte-mediated cytolysis. PMID- 1502976 TI - The central role of follicular dendritic cells in lymphoid tissues. PMID- 1502978 TI - [The local immune system of ocular surface]. AB - Local immunity on the ocular surface was observed in guinea pigs immunized with horseradish peroxidase (HRP) by determining the activity of a specific antibody in local sites of the conjunctiva by the enzyme-antigen method, which enables a specific antibody to be stained. In addition, immunohistochemical study of the localization of IgA was performed by the enzyme-labelled antibody method. The enzyme-antigen method revealed a number of positive cells in the subconjunctival tissue and the parafollicular area of conjunctival-associated lymphoid tissue. These cells were identified as plasma cells by electron microscopy. The mirror section technique revealed that the cells positive for the enzyme-antigen method were consistent with anti-IgA-positive cells at many sites. Thus the distribution of plasma cells secreting IgA-specific antibody responsible for local immunity on the ocular surface was observed immunohistochemically. The results suggest that immunocytes in the conjunctival-associated lymphoid tissue differentiate and mature into specific antibody-producing plasma cells. PMID- 1502977 TI - The pathobiology of bronchial asthma. AB - Early studies of patients dying from status asthmaticus revealed marked inflammation of the bronchial tree. Subsequent histological studies of the airways and examination of bronchoalveolar lavage fluid of subjects with mild asthma have confirmed the presence of airway inflammation in life. There is epithelial edema and desquamation, subepithelial deposition of collagen and fibronectin, and an inflammatory cell infiltrate in the mucosa. There are increased numbers of activated eosinophils, CD25-positive T lymphocytes, and immature macrophages with the phenotypic characteristics of blood monocytes. An increased expression of HLA class II is present on epithelium, macrophages, and other infiltrating cells. The severity of clinical asthma correlates with several measurements of the severity of the inflammatory response, suggesting a crucial role for airway inflammation in the pathophysiology of the disease. There is considerable interest and research into the mechanisms underlying the pathogenesis and maintenance of the inflammatory response in asthma. The development and maintenance of the inflammatory response in asthma is likely to be a consequence of a complicated interaction between various cells and the mediators they generate. The characterization of an ever-increasing number of cytokines is of particular interest. Interleukin-3, interleukin-5, and granulocyte-macrophage colony-stimulating factor are hematopoietic growth factors that increase the survival of eosinophils in culture and enhance certain eosinophil functions, such as mediator generation and toxicity. Alveolar macrophages derived from asthmatic subjects produce twofold to threefold more GM CSF than do those from normal control subjects. Using in situ hybridization, the presence of IL-5 mRNA has been demonstrated in bronchial biopsies from asthmatic subjects. Thus IL-3, IL-5, and GM-CSF influence eosinophil function and survival, and may be generated by T lymphocytes and/or alveolar macrophages within the airways in asthma. In addition to these three cytokines, IL-4 and interferon gamma may be crucial to the regulation of IgE biosynthesis. TNF-alpha and IL-1 are potentially important in the up-regulation of endothelial adhesion molecules. An important step in the recruitment of leukocytes to an inflammatory focus is margination to the vascular endothelium. Our understanding of the molecular events involved in migration of leukocytes to an inflammatory focus has been advanced by the discovery and characterization of a variety of cell adhesion molecules. The potential role of ELAM-1 and ICAM-1 in allergic inflammation is suggested by their up-regulation on vascular endothelium in association with late cutaneous responses to allergen and by their role in certain primate models of asthma.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1502979 TI - [A flow cytometric study of the effects of benzalkonium chloride on the cell cycle]. AB - The effects of benzalkonium chloride (BAK) on the cell cycle of Chang's cultured human conjunctival cells were investigated by a flow cytometer (FCM). The cells were exposed to BAK solutions for 60 sec and after 12-48 hrs were fixed in 20% ethanol, treated by 0.25% RNase and stained by 0.005% propidium iodide. DNA histograms were analyzed by the FCM. As a result, although many cells were damaged by exposure to solutions of 0.0025% or 0.005% BAK, they began to grow again 48 hrs later. BAK decreased red fluorescence intensity in DNA histograms. The histogram shifted to the left 12 hrs after the cells were exposed to 0.0025% or 0.005% BAK solutions and recovered 48 hrs later. The DNA synthetic phase of the cell cycle was inhibited by exposure to solutions of 0.0025% BAK and then recovered 48 hrs later. PMID- 1502980 TI - [Metabolic analysis of the diseased human corneal endothelium]. AB - Redox states of the corneal endothelium in 42 recipient corneas obtained at the penetrating keratoplasty were measured non-invasively using ocular redox fluorometry. Autofluorescence from reduced pyridine nucleotides (PN) and oxidized flavoproteins (Fp) were measured, and the PN/Fp ratio was used as an indicator of the redox state. Endothelial damage was graded as normal, mildly damaged, moderately damaged, and severely damaged, based on the histopathological findings. Mildly damaged endothelium showed a significantly higher PN/Fp ratio than the that in normal endothelium whereas the ratio was significantly lower in the severely damaged endothelium. These changes in the redox state may represent compensation and decompensation processes of the endothelial metabolism. Ocular redox fluorometry was shown to be useful for the evaluation of the metabolic state in the human corneal endothelium. PMID- 1502981 TI - [The immunosuppressive effects of 0.025% cyclosporin eye drops in alpha cyclodextrin on rabbit corneal allografts]. AB - We reported the ocular penetration of cyclosporin (CYA) and the immunosuppressive effect of rabbit corneal allograft using 0.025% CYA eye drops in alpha cyclodextrin (alpha-CD). Local application using 0.025% CYA in alpha-CD showed the concentration of 4,133 ng/gr in the cornea, but no detectable levels in aqueous humor and serum. All eyes (10/10) in the CYA eye drop group remained clear for 100 days after corneal allografting. CYA eye drops halted and suppressed the corneal allograft's immune reaction when the treatment was begun early in the initial phase of rejection. These results indicate that 0.025% CYA eye drops in alpha-CD penetrate the cornea 5 to 10 times more than CYA eye drops in lipophilic vehicles. Furthermore, they are extremely effective in suppressing the immune reaction of corneal grafts. PMID- 1502982 TI - [Investigation of glutathione-S-transferase isozymes in human lenses]. AB - Glutathione-S-Transferase (GST) isozymes in human lenses were investigated by the immunoenzymatic method using antibody against human liver GST2 and GST3 after polyacrylamide gel isoelectric focusing (western blotting method). Also, rocket immunoelectrophoresis was carried out for the detection of GST1. It was found that GST1 in lens also showed a polymorphism. The GST2 was not found in human clear lenses as well cataractous lenses. In addition, crossreacting materials against both antisera of GST2 and 3 were detected in the pH 6-7 area of the gel in all human lenses. PMID- 1502983 TI - [Changes in rabbit lens epithelial cells after intravitreal silicone oil injection]. AB - Using adult albino rabbits, the clinical course of lens opacity and morphological changes of lens epithelial cells were observed from 2 weeks to 3 months after intravitreal silicone oil injection. Simple vitrectomy was performed in both rabbit eyes. One eye with silicone oil injection served as an experimental eye, while another control eye did not receive any injection. Seven examined eyes showed early posterior subcapsular lens opacity from one month after silicone oil injection by slit-lamp microscopy. Small intracellular vacuoles near to the interdigitation of the lens epithelial cells were observed in the 7 eyes from 2 weeks after the procedure by transmission electron microscopy. These changes were not observed in 7 control eyes. As a result, it is surmised that cataract formation after intravitreal silicone oil injection may be associated with morphological changes of the lens epithelial cells. PMID- 1502984 TI - [Dynamic changes in the organophosphate metabolites of the lenses affected by endotoxin and S-antigen induced uveitis]. AB - Using 31P-NMR spectroscopy, the authors observed dynamic changes in the organophosphate metabolites in the lenses of two groups of Lewis rats affected by experimental uveitis induced by injecting Salmonella lipopolysaccharide (n = 20) or S-antigen (n = 25). A comparative study was done on the metabolic changes, the degree of inflammation, and histological changes in the rat lenses. Dynamic changes in the organophosphate profile in the lenses were measured by 31P-NMR spectroscopy. Only inorganic phosphate showed a significant increase (p less than 0.05) related to the increased inflammation in the endotoxin group, but the lenses showed no morphological change. Choline phosphate, adenosine triphosphate, and inorganic phosphate increased significantly (p less than 0.01) in the acute stage of inflammation, but a significant decrease (p less than 0.01) was evident from the peak of inflammation, following the histological destruction of the lenses. Our results indicated that in experimental uveitis dynamic changes in the organophosphate profile of the lenses were closely related to the protecting reaction against the stress caused by inflammation. Furthermore, we theorized that the generation of the secondary cataract was associated with the decreased metabolism of the phosphate compounds. PMID- 1502985 TI - [Ciliary body changes associate with aldose reductase in galactosemic rats (2)]. AB - Morphological changes of the ciliary body epithelium in rats fed a 50% galactose diet for 18 months with or without aldose reductase inhibitor (ARI: FR74366, Fujisawa) were investigated on coronal sections by both the light microscopic observation and the measurement of the area of non-pigmented epithelium (non-PE) as the ratio of non-PE/PE. The measurement was performed with color image analyzer. Structural change (hypertrophy) was observed only in non-pigmented epithelial cells of galactosemic rats. In contrast, no hypertrophic changes were seen in galactosemic rats treated with FR74366. These results strongly suggest that aldose reductase is associated with hypertrophic change of non-pigmented epithelial cells of the ciliary body as one of the diabetic complications. PMID- 1502986 TI - [Possible mechanisms of inositol phosphate-diacylglycerol signalling pathway in the regulation of intraocular pressure]. AB - To clarify the role of the inositol phosphate diacylglycerol (IP/DAG) signalling pathway in the regulation of intraocular pressure (IOP), the effect of tumor promoter phorbol ester (PMA) and Ca ionophore (A23187) on IOP responses was examined in albino rabbits. PMA stimulates protein kinase C (PKC) directly and A23187 elevates intracellular Ca2+ concentration. In this study, the topical application of 10 microM PMA or 15 microM A23187 slightly reduced IOP. However topical application of both 10 microM PMA and 15 microM A23187 significantly reduced IOP. The maximum IOP decrease was 5.0 mmHg. This decrease was inhibited by pretreatment with 0.5 microM staurosporin, a PKC inhibitor. Quantitative changes of inositol 1,4,5-trisphosphate (IP3) and PKC activity in cultured ciliary epithelia (CE), stimulated with several ocular hypotensive agents were also studied. When cultured CE was stimulated with 50 microM carbachol, the PKC activity and IP3 content rapidly increased. When CE was stimulated with 50 microM epinephrine, isoproterenol or timolol, PKC activity did not show any change and IP3 level declined. These studies suggest that the IP/DAG signalling pathway somehow mediates aqueous dynamic changes in ciliary epithelia. PMID- 1502987 TI - [Measurement of blood velocity of rabbit iris by laser speckle flowgraphy]. AB - We developed laser speckle flowgraphy which displays the relative velocity of blood microcirculation as a color map in two dimensions. We applied this method to the iris in 10 eyes of 5 normal white rabbits under general anesthesia. The coefficient of variation was small and averaged 5.6. There was no significant difference in the values measured on 3 consecutive days. The blood velocity in the iris increased significantly during experimental ocular hypotony and decreased during ocular hypertension and 2 hours after instillation of timolol (p less than 0.05). These findings indicate that the present method is of value in assessing the relative velocity of iris microcirculation in vivo and that topical instillation of timolol induces decrease of blood flow in the iris and, possibly, in the ciliary body. PMID- 1502988 TI - [Effects of carteolol on electroretinograms in isolated perfused cat eye]. AB - Effects of carteolol on ERG b-wave amplitude were investigated in dark adapted isolated perfused cat eyes. Carteolol enhanced ERG b-waves with both strong stimuli that reflect the function of both the rod and cone systems, and weak stimuli that reflect the function of the rod system. These observations suggest the following two ideas i.e.: 1. Carteolol increases the flow in retinal vessels of perfusate. or 2. Carteolol has interaction with retinal beta-adrenergic receptors related to the origin of the ERG b-wave. It is likely that both participate in the intrinsic sympathomimetic activity and the release activity of the endothelium derived relaxing factor of carteolol. PMID- 1502989 TI - [Transient patterns of serotonergic innervation in the rat visual cortex--normal development and effects of enucleation]. AB - Serotonergic innervation formed transient dense aggregation in all rat primary sensory areas during early postnatal development. In the normal rat visual cortex, there were three stages in the transient aggregation of serotonin immunoreactive fibers from postnatal day (PND) 2 to 15. Primary aggregates appeared in the subplate prior to the differentiation of layer IV, and moved upward to the lower layer of cortical plate to form secondary aggregates. Secondary aggregation gave rise to ascending fibers on the cortical surface which were roughly grouped in columns (tertiary aggregation). The serotonin fibers of the tertiary aggregates were arranged in a lattice-like pattern in layer I, and were significantly altered either in size of distribution area or column number after monocular or binocular enucleation. These data indicate that the lattice like pattern of serotonin innervation in neonatal rats may be an evolutionary precursor of the "blobs" seen in the higher primates. PMID- 1502990 TI - [Natural history of intermittent exotropia--statistical study of preoperative strabismic angle in different age groups]. AB - To clarify the natural history of intermittent exotropia, the authors statistically analysed the size of deviations between the initial and the last visit of unoperated intermittent exotropes. In younger patients who were followed for over five years, the magnitudes were almost the same throughout the follow-up periods. A statistical analysis of preoperative strabismic angles in operated cases of different age groups was also done. From comparable studies of the preoperative size of exodeviations in three different age groups, the deviations in distance fixation in adults were apparently larger than in children. We think the size of the deviation in distance fixation tends to increase with aging, but the increase was not so great for the older adult group. However, the size of the deviation in near fixation tended to steadily increase throughout aging, showing statistical significance among all three groups, children, adults in their twenties and thirties, and adults over forty. In the over forty group, the convergence insufficiency type of deviation was present in the majority. PMID- 1502991 TI - [Evaluation of preoperative prism adaptation in patients with acquired esotropia]. AB - A prospective study was carried out of the evaluation preoperative prism adaptation in 77 patients with acquired esotropia. Sixty-three patients who showed a stable esodeviation with prisms of 10 prism diopter or less by alternate prism cover test and fusion response to the prisms were classified as prism responders and were randomly classified into two groups. Thirty-one patients of prism responders underwent surgery based on the prism adapted angle. Patients in the other 32 cases were assigned to undergo surgery for their initially measured angle. On the other hand, 14 patients who did not respond to prism adaptation underwent surgery for their preoperative measured angle of deviation. Success rates with deviations of 0 to 10 prism diopters measured 1 year after surgery by the alternative prism cover test at 5 m and with fusion on Bagolini's striated glasses test were highest (26 [84%] of 31 patients) in prism adaptation responders who underwent surgery for prism determined angle and lowest (3 [21%] of 14 patients) in the prism adaptation nonresponder who showed no fusion response to the prisms. PMID- 1502992 TI - [Frequency response of ocular counter-rolling analyzed with passive sinusoidal head roll]. AB - Using a computerized motor-driven chair that oscillates the subject's head in the frontal plane and a real-time video processing system for analyzing torsional eye movements, the frequency response of ocular counter-rolling to passive, sinusoidal head rolling was studied in darkness in 3 normal subjects. The gain of counter-rolling increased its mean value from 0.22 (0.17 Hz) to 0.52 (1.33 Hz) along with the frequency of head oscillation. Its phase error with respect to ideal compensation was slight (173-181 deg). Furthermore, the gain of counter rolling was increased slightly from 0.31 (+/- 5 deg) to 0.39 (+/- 20 deg) along with the amplitude of head oscillation. Our experimental results agreed with the characteristics of the frequency responses for voluntary head shaking previously reported by Collewijn and colleagues, except that counter-rolling had a slightly lower gain. PMID- 1502993 TI - [A case of peripheral corneal ulcer accompanied by progressive systemic sclerosis]. AB - A 61-year-old woman with progressive systemic sclerosis developed bilateral peripheral corneal ulcer. The corneal lesions were resistant to daily systemic treatment with 15 mg steroid and 50 mg cyclophosphamide. Corneal perforation occurred in her right eye 11 months after the onset of Raynaud's phenomenon and 3 months after the scleritis. Lamellar keratoplasty accompanied with Brown's operation was performed on both eyes. Graft melt and cicatricial corneal opacity developed postoperatively. Removed conjunctival tissue was examined immunohistochemically. HLA-DR protein positive monocytes infiltrated subepithelial tissue, demonstrating that the inflammation of the lesions was in the active stage. Not only perforin but also suppressor/cytotoxic T cell positive reactions were observed, which revealed an involvement of the T cell immune system in the present case. PMID- 1502994 TI - Ketamine, Telazol, xylazine and detomidine. A comparative anesthetic drug combinations study in ponies. AB - This study was designed to assess the effects of 5 anesthetic drug combinations in ponies: (1) ketamine 2.75 mg/kg, xylazine 1.0 mg/kg (KX), (2) Telazol 1.65 mg/kg, xylazine 1.0 mg/kg (TX), (3) Telazol 2 mg/kg, detomidine 20 micrograms/kg (TD-20), (4) Telazol 2 mg/kg, detomidine 40 micrograms/kg (TD-40), (5) Telazol 3 mg/kg, detomidine 60 micrograms/kg (TD-60). All drugs were given iv with xylazine or detomidine preceding ketamine or Telazol by 5 min. Heart rate was decreased significantly from 5 min to arousal after TD-20 but only at 60 and 90 min after TD-40 and TD-60 respectively. Respiratory rate was decreased significantly for all ponies. Induction time did not differ between treatments. Duration of analgesia was 10 min for KX, 22.2 min for TX, 27.5 min for TD-20, 32.5 min for TD 40, and 70 min for TD-60. Arousal time was significantly longer with detomidine and Telazol. Smoothness of recovery was judged best in ponies receiving KX and TD 40. All ponies stood unassisted 30 min after signs of arousal. PMID- 1502995 TI - The role of endotoxins in induced ruminal acidosis in calves. AB - Experimentally induced ruminal acidosis was carried out in 4 calves to investigate the possibility of resorption of endotoxins from Gram negative bacteria originating from the gastro-intestinal tract. The ruminal acidosis was induced by overfeeding of oats and the effect was evaluated by clinical and blood biochemical changes. Blood samples were collected every 2 h for 60 h before and after experimental feeding. The animals showed signs of ruminal acidosis and also the clinical and blood biochemical changes were similar to those seen after experimental endotoxaemia. However, although being less dramatic the changes in many relevant parameters such as an increase in prostaglandin F metabolite levels, body temperature, endotoxins and a decrease in iron indicate that an endotoxaemic state had occurred. The results of the present study show that ruminal acidosis/stasis is linked to resorption of endotoxins from the gastro intestinal tract causing endotoxaemia/endotoxicosis. PMID- 1502996 TI - The role of endotoxins in methscopolamine induced ruminal stasis in calves. AB - Methscopolamine was used to induce ruminal stasis in calves. Clinical and blood biochemical parameters were studied to judge the possible role of gastro intestinal endotoxins from Gram-negative bacteria. Two trials were carried out where one injection of 100 mg and 3 consecutive injections of 70 mg of methscopolamine were administered. The animals showed signs of ruminal stasis. General clinical signs and changes in blood biochemical parameters were similar to what is found in endotoxaemia or in induced ruminal acidosis. Relevant parameters such as prostaglandin F2 alpha metabolite, endotoxin, iron, zinc, calcium and glutamate dehydrogenase changed significantly indicating exposure of endotoxins. PMID- 1502997 TI - Effect of hypophosphatemia on muscle metabolism after exercise in pigs. AB - Five Swedish Landrace pigs with a mean weight of 51 +/- 5 kg performed an exercise test on a treadmill at a speed of 1.8 m/s and a duration of 10 min. Hypophosphatemia was then induced in these pigs by addition of aluminium hydroxide (liquid antacid) to the normal feed. After 3 weeks, the exercise test was repeated when the mean weight of the pigs was 65 +/- 9 kg. Five other Swedish Landrace pigs with a mean weight of 72 +/- 4 kg performed a similar exercise test. Muscle biopsies from M. biceps and blood samples were taken from all pigs 3 5 days before and immediately after each exercise test. Hypophosphatemic pigs had significantly lower serum phosphate and higher aluminium levels than normophosphatemic pigs. In all pigs, glycogen content in muscle decreased significantly (-108 to -135 mmol/kg muscle) with exercise while no changes were seen in adenosine triphosphate, creatine phosphate or inorganic phosphate concentrations. In normophosphatemic pigs, glucose-6-phosphate and lactate concentrations increased significantly during exercise by 2-4 mmol/kg and 12.8 14.4 mmol/kg, respectively. However, in hypophosphatemic pigs, glucose-6 phosphate concentrations decreased significantly during exercise by 4.4 mmol/kg and lactate levels were unchanged. These results indicate that low serum inorganic phosphate levels influence muscle metabolism and glycolysis in connection with physical exercise. PMID- 1502998 TI - Early foetal death in the mare. Histological, bacteriological and cytological findings in the endometrium. AB - Fifteen mares which had each lost their pregnancies 2 to 8 times during the preceding 6 years were used in a study comprising 1 or 2 breeding seasons for each mare. During the research period all 15 mares conceived and 10 of the mares had normal pregnancies in the 1st experimental year. Five mares resorbed/aborted once or twice during the 1st year. This was followed by a pregnancy that terminated in a live foal. Histopathological examinations of uterine biopsies showed a wide range of histopathological conditions, from absence of changes excessive for the mare's age and parity to the most severe changes of the endometrium. Most likely, endometritis, acute as well as chronic degenerative endometritis, is the most common cause of early foetal death in the mare. Good breeding management is essential and was often enough to make the mares produce a foal. Additional treatment was needed in some of the mares and was based on the course of the conceptus loss and the condition of the endometrium, as determined by clinical, histological, bacteriological and cytological examinations. PMID- 1502999 TI - Occurrence of infectious fish diseases in fish farms in northern Finland. AB - A total of 47 fish located in 10 lake and river systems in northern Finland were examined for furunculosis, enteric redmouth diseases (ERM), viral fish diseases and the parasite Gyrodactylus salaris. Furunculosis was found in 2 fish farms in different watercourses, ERM in 8 fish farms in 3 watercourses and viral diseases were not found at all. G. salaris was looked for only in salmon and rainbow trout and was found in both species in 3 farms belonging to 2 watercourses. PMID- 1503000 TI - Occurrence of different serotypes of Erysipelothrix rhusiopathiae in retail pork and fish. AB - Retail pork (38 samples), cod (10 samples) and herring (10 samples) were obtained from 12 stores in the area of Lund in southern Sweden during September and October 1990. Erysipelothrix rhusiopathiae was isolated from 50% of the pork samples, 60% of the cod samples and from 30% of the samples from herring. Serotype 2 dominated on retail pork as well as on fish samples constituting 53% of the pork isolates (10 strains) and 33% of the cod isolates (2 strains). All E. rhusiopathiae isolates originating from herring were serotype 2 (3 strains). Serotypes 1b, 6, and 8 were isolated from retail pork only (6, 2 and 1 strains, respectively). Serotype 5 was isolated from cod only (3 strains) and so was serotype 9 (1 strain). The public health hazards with the occurrence of virulent strains of Erysipelothrix rhusiopathiae in retail pork and fish are discussed. PMID- 1503001 TI - Toxoplasmosis and border disease in 54 Swedish sheep flocks. Seroprevalence and incidence during one gestation period. AB - Serum samples from 704 animals from 54 Swedish sheep flocks were analysed by ELISA twice during 1 breeding season for antibodies to Toxoplasma gondii and border disease virus (BDV). An ELISA, originally developed for the detection of antibodies to bovine viral diarrhoea virus (BVDV) in cattle, was assessed on sheep sera and the results were compared with those obtained in a virus neutralization test. The correlation between the 2 assays proved good. Before breeding, 132 (19%) sheep in 42 flocks had antibodies to T. gondii and 7 (1%) sheep in 5 flocks were seropositive to BDV. During the observation period 4 sheep seroconverted to T. gondii and 13 to BDV, giving an incidence rate of 0.7% and 1.9% respectively. No clinical signs due to the infections were observed. In 5 flocks the frequency of barrenness, abortion or stillbirths exceeded 5%, 5% and 8%, respectively, but there was no evidence that this was attributable to the agents studied. The proportion of BDV-positive flocks was significantly higher among flocks that had been in contact with cattle than among those that had not. PMID- 1503002 TI - Trace elements, minerals, retinol and alpha-tocoferol in calves persistently infected with bovine virus diarrhoea virus. PMID- 1503003 TI - Diurnal changes in the leucogram of ovariectomized gilts. PMID- 1503004 TI - MR measurement of blood flow in the cardiovascular system. AB - Methods for measurement of blood flow with MR were devised many years ago but have been used for diagnosis in only the past few years. The two methods of measurement that have been used most extensively are based on the principles of time of flight and phase shift. A number of factors can influence the accuracy of MR measurements of blood flow. In vitro studies using flow phantoms have verified the accuracy of the phase-shift technique for measuring flow velocities exceeding 5 m/sec, which for practical purposes, encompasses the peak flow encountered in cardiovascular disorders. The flow measurements have been used to quantify valvular heart disease, congenital heart disease, pulmonary arterial disease, thoracic aortic disease, and peripheral vascular disease. PMID- 1503005 TI - Conquerors of yellow fever. PMID- 1503006 TI - Diagnosis of bronchiolitis obliterans in heart-lung transplantation patients: importance of bronchial dilatation on CT. AB - OBJECTIVE: The purpose of this study was to evaluate the significance of bronchial dilatation identified on high-resolution CT scans obtained after heart lung transplantation. Bronchial dilatation has been identified on pathologic specimens and on high-resolution CT scans of patients with severe bronchiolitis obliterans after lung transplantation, but this finding has not previously been systematically studied as a manifestation of this complication. MATERIALS AND METHODS: We studied the high-resolution CT scans of 16 patients who had had heart and lung transplantation at least 1 year before, and compared the percentage of dilated bronchi with evidence of small airways disease shown on pulmonary function tests. RESULTS: We found a close correlation between the percentage of bronchi in the lower lobes that were dilated and the percent predicted forced expiratory volume in 1 sec, forced vital capacity, and forced expiratory flow between 25% and 75% of vital capacity. No other feature identified on high resolution CT scans correlated with pulmonary function abnormalities. CONCLUSION: We conclude that dilatation of the lower lobe bronchi is a good indicator of bronchiolitis obliterans in this population, and that the percentage of dilated bronchi generally increases with increasing pulmonary dysfunction. PMID- 1503007 TI - Hypersensitivity pneumonitis: sensitivity of high-resolution CT in a population based study. AB - OBJECTIVE: Hypersensitivity pneumonitis refers to a group of pulmonary disorders caused by inhalation of organic or inorganic particulates by sensitized persons. The diagnosis relies on a constellation of findings: exposure to an offending antigen, characteristic signs and symptoms, abnormal chest findings on physical examination, and abnormalities on pulmonary function tests and radiographic evaluation. In population-based studies, the sensitivity of chest radiography for detection of this disease is relatively low. The aim of this study was to determine the sensitivity of high-resolution CT (HRCT) for detection of hypersensitivity pneumonitis diagnosed in a population of swimming-pool employees. SUBJECTS AND METHODS: Thirty-one symptomatic employees of a recreation center who were referred because of possible hypersensitivity pneumonitis were examined by using chest radiography, HRCT, and fiberoptic bronchoscopy with bronchoalveolar lavage and transbronchial biopsy. Hypersensitivity pneumonitis was diagnosed in subjects who had two or more work-related signs or symptoms, abnormal results on transbronchial biopsies, and abnormal lymphocytosis as shown by examination of bronchoalveolar lavage fluid. The chest radiographs and HRCT scans were interpreted by consensus by two observers who were unaware of the clinical diagnosis. RESULTS: Only one of 11 subjects with a diagnosis of hypersensitivity pneumonitis had abnormal findings on a chest radiograph. Five had abnormal HRCT findings. The abnormality in each case consisted of small, poorly defined centrilobular nodules with variable profusion. No subject without the disease had abnormal HRCT findings. Those who had granulomas shown by lung biopsy were more likely to have abnormal HRCT findings than were those who had more subtle histologic abnormalities. CONCLUSION: The sensitivity of HRCT for the detection of hypersensitivity pneumonitis in a population-based study is greater than that of chest radiography. The finding of poorly defined centrilobular nodules on HRCT scans should prompt consideration of this disease. PMID- 1503008 TI - Pulmonary sarcoidosis: changes on follow-up CT examination. AB - OBJECTIVE: To determine serial changes in the pattern, distribution, and extent of disease over time, and to determine if any specific findings could be used to predict prognosis in patients with pulmonary sarcoidosis, we reviewed the CT scans of 18 patients with pulmonary sarcoidosis. MATERIALS AND METHODS: The study included 18 patients with biopsy-proved sarcoidosis and pulmonary abnormalities who had two serial high-resolution CT examinations (1.5-mm collimation, high spatial-frequency reconstruction algorithm) 4-49 months apart. Initial and follow up CT scans were evaluated independently and then directly compared with each other by two observers. Scans were assessed for the presence, extent, and severity of ground-glass, nodular, and irregular linear opacities; interlobular septal thickening; cystic air spaces; and architectural distortion. If a finding was predominant, it was noted. RESULTS: Reversible findings included ground glass, nodular, and irregular linear opacities and septal thickening. Irreversible findings included cystic air spaces and architectural distortion. Follow-up CT showed overall improvement in 12 of 18 patients, progression in five, and no change in one. A predominant pattern of disease could be determined for each patient. Fourteen patients had predominant nodular opacities; of these, 11 had improved by follow-up. Four had predominant irregular linear opacities; of these, three showed progression of disease on follow-up. The presence of any other specific abnormalities, including ground-glass opacities, was not helpful in predicting improvement or worsening of disease on the follow-up examination. CONCLUSION: In pulmonary sarcoidosis, ground-glass, nodular, and irregular linear opacities and interlobular septal thickening represent potentially reversible disease, while cystic air spaces and architectural distortion are irreversible findings. Follow-up CT usually shows improvement in patients with predominant nodular opacities, while disease tends to progress in patients with predominant irregular opacities. PMID- 1503009 TI - Anomalous left brachiocephalic (innominate) vein: MR demonstration. PMID- 1503010 TI - Value of MR imaging in detecting a peanut causing bronchial obstruction. PMID- 1503011 TI - Solitary breast papilloma: comparison of mammographic, galactographic, and pathologic findings. AB - OBJECTIVE: Our purpose was to determine the mammographic/galactographic features of solitary breast papillomas and to correlate these features with the pathologic findings. MATERIALS AND METHODS: Retrospective review of pathology files revealed 72 women in whom breast biopsy reports described a solitary papilloma. All patients with additional pathologic abnormalities were excluded from this study. Patients meeting the pathologic criteria and for whom mammograms, galactograms, or both were available and had been obtained within 6 months before biopsy were included. Twenty-four women met these criteria and form the basis of this study. Presenting clinical signs and symptoms were reviewed. Abnormal mammographic/galactographic findings were correlated with pathologic features. RESULTS: Nipple discharge was present in 21 (88%) of 24 patients, two (8%) of 24 patients had abnormal findings on screening mammography, and one patient had a palpable mass that was visible on mammograms. Eight (42%) of 19 mammograms had abnormal findings, including dilated duct(s) in five cases (26%), nodules in two cases (11%), and microcalcifications in one case (5%). All technically adequate galactograms (13/15) had abnormal findings, with 12 (92%) of 13 showing an intraluminal filling defect. The other technically adequate galactogram (8%) showed only a solitary obstructed duct. Ductal dilatation was greatest at or central to the papilloma on 12 (92%) of 13 galactograms. Imaging features correlated well with the histologic findings. CONCLUSION: Patients with solitary papillomas most commonly have nipple discharge, normal mammographic findings, and a galactographic filling defect. Galactography is useful for localizing papillomas. PMID- 1503012 TI - Mammography in women with axillary lymphadenopathy and normal breasts on physical examination: value in detecting occult breast carcinoma. AB - OBJECTIVE: The purpose of this study was to determine the value of mammography in detecting occult carcinoma in patients with axillary adenopathy and normal breasts on physical examination. MATERIALS AND METHODS: We analyzed the results of mammography performed in 17 patients; all women had palpable axillary lymphadenopathy of unknown origin and all had normal breasts on physical examination. RESULTS: In 10 of the 17 patients, mammographic findings were abnormal. The mammographic finding of axillary adenopathy in seven patients was inconsequential because the nodes were evident on physical examination. Three patients had abnormal mammographic findings that were potentially significant, including one with a poorly defined mass suggestive of breast carcinoma, one with a subcutaneous nodule, and one with parenchymal breast edema. Two of 17 patients had an occult breast cancer. In only one of the patients was the cancer detected on mammography. The other patient had undergone prior left mastectomy and was thought to have metastases to the right axilla from the contralateral breast. Mammographic findings in this latter patient were normal. CONCLUSION: While occult breast carcinoma was relatively common in our series (two of 17 patients), the ability to detect the tumor with mammography was disappointing (one of two patients). This may be explained by the fact that one postmastectomy patient with occult carcinoma had metastatic disease to the contralateral axilla and a normal remaining breast, which was pathologically confirmed at mastectomy. Our experience suggests that mammography is valuable in patients with normal breasts on physical examination who have primary carcinoma involving ipsilateral axillary lymph nodes. The procedure should be included in the diagnostic evaluation of patients with axillary adenopathy in order to detect the unusual case of occult breast carcinoma. PMID- 1503013 TI - Left-lobe hepatic transplants: spectrum of normal imaging findings. AB - The limited availability of suitable size-matched donor whole organs has been a major cause of morbidity and mortality in infants and children requiring liver transplantation. Techniques for transplanting segments of the liver have successfully addressed this problem. The surgical anatomy of the left hepatic lobe transplant is unique in three primary respects: the cut edge, the presence of an enteric Roux loop for biliary drainage, and the alteration in the position and number of hepatic vessels. The spectrum of normal imaging findings in 17 left lobe allografts is illustrated. PMID- 1503014 TI - Chronic biliary-type pain in the absence of gallstones: the value of cholecystokinin cholescintigraphy. AB - Radiologic criteria for the diagnosis of gallbladder disease largely rest on the detection of calculi. Surgeons are reluctant to do a cholecystectomy in patients with symptoms of gallbladder disease if the results of sonography or cholecystography are normal. Consequently these patients are often left with no satisfactory treatment. Such patients may have chronic acalculous cholecystitis, partial obstruction of the cystic duct, or gallbladder dyskinesia. Increasing evidence indicates that at least some of these patients have decreased gallbladder emptying in response to a stimulus such as a test meal or cholecystokinin. Impaired emptying shown by cholecystokinin cholescintigraphy may be useful for predicting which patients with typical biliary-type pain but no evidence of calculi will be cured by cholecystectomy. PMID- 1503015 TI - Membranous obstruction of the inferior vena cava: comparison of findings at sonography, CT, and venography. AB - OBJECTIVE: Membranous or segmental obstruction of the inferior vena cava is one of the common causes of chronic Budd-Chiari syndrome. In this study, the venographic findings are compared with the results of sonography and CT in order to ascertain their role in the management of these cases. MATERIALS AND METHODS: Fifteen patients with membranous (n = 8) or segmental (n = 7) obstruction of the inferior vena cava who had been examined with sonography and CT were studied retrospectively. Diagnosis was made at surgery (n = 3) or by venacavography (n = 12). Sonographic findings were analyzed on the basis of the initial report, and CT findings were reviewed retrospectively with knowledge of the sonographic findings. RESULTS: Sonography showed membranous obstruction (n = 5), segmental cordlike obstruction (n = 3), and unspecified obstruction (n = 5) of the inferior vena cava, while CT showed a flap of the membrane (n = 1) and segmental narrowing or obstruction of the inferior vena cava (n = 7). In the remaining cases, the inferior vena cava either appeared normal (n = 6) or was not visualized (n = 1) on CT or was not described in the sonographic report (n = 2). In nine cases, CT showed one or several tiny calcific foci in the inferior vena cava. Sonography showed obliteration of at least one hepatic vein (n = 8) and of intrahepatic collateral vessels (n = 12), whereas CT was less sensitive in evaluating obliteration of intrahepatic veins (n = 4) and collateral vessels (n = 7). Sonography and CT both showed hepatic masses (n = 6), evidence of liver cirrhosis and portal hypertension (n = 14), hepatomegaly (n = 14), enlargement of the caudate lobe (n = 9), and intraabdominal (n = 11) and abdominal wall (n = 15) collateral vessels. CONCLUSION: Sonography was superior to CT in delineating pathologic venous anatomy of the inferior vena cava and hepatic veins whereas CT was better in evaluating hepatic cirrhosis and tumor. We believe that these techniques are useful complements to venography in the diagnosis and management of these cases. PMID- 1503016 TI - Acute lower gastrointestinal hemorrhage: treatment by superselective embolization with polyvinyl alcohol particles. AB - OBJECTIVE: The major risk of transcatheter embolotherapy for acute hemorrhage in the lower gastrointestinal tract is irreversible intestinal ischemia. The authors studied the efficacy and safety of superselective transcatheter embolization with polyvinyl alcohol particles in arresting acute hemorrhage in the lower gastrointestinal tract. SUBJECTS AND METHODS: All patients with clinical or scintigraphic evidence of acute hemorrhage in the lower gastrointestinal tract were considered for superselective embolization. The nine patients with angiograms that showed active hemorrhage in the lower gastrointestinal tract underwent the procedure. Superselective embolization was done through a 3-French catheter and was accomplished by using 100- to 590-microns polyvinyl alcohol particles. The segments of the intestinal tracts involved in the embolizations were examined for the presence of ischemia by endoscopy (n = 7) or histologic evaluation of a surgical specimen (n = 2) 2-44 days (mean, 11 days) after embolization or by clinical evaluation (n = 1). RESULTS: The lesions treated by this method were located in the colon (n = 8) and jejunum (n = 1). Immediate hemostasis was achieved in every case. Three patients had recurrent lower gastrointestinal hemorrhage 1-24 days (mean, 9 days) after initial embolization. Two of these patients had surgery, while one had a successful second embolization. Two asymptomatic patients were found endoscopically to have small areas of ischemia involving only the mucosa. Only one patient was shown to have severe mucosal ischemia; this involved the colon in a distribution that suggested it was not caused by the embolization. CONCLUSION: Ten superselective embolization procedures that used polyvinyl alcohol particles successfully controlled hemorrhage in the lower gastrointestinal tract in nine patients. In no case was intestinal infarction induced by the procedure, and only two endoscopically proved cases of asymptomatic mucosal ischemia occurred. PMID- 1503018 TI - Pancreatic disease: findings on state-of-the-art MR images. AB - Recent technical innovations have made MR imaging a useful technique for imaging the pancreas. The potential impact of MR imaging on the management and outcome of cases can be determined only by controlled prospective comparative studies; however, these cannot be performed adequately until the normal and abnormal appearances of the pancreas on state-of-the-art MR images are understood. This pictorial essay is presented to further this intermediate goal. PMID- 1503017 TI - The density, contour, and thickness of the pancreas in diabetics: CT findings in 57 patients. AB - Insulin has a trophic effect on pancreatic acinar tissue, so the pancreas might be expected to atrophy in persons who have diabetes. Accordingly, we analyzed the density, contour (smooth or lobulated), and thickness of the pancreas on CT scans of diabetic patients and compared the results with those in control subjects. The prevalence of pancreatic lobulation (incisurae deeper than 2 mm) and its correlation with age in diabetic and control subjects were determined. The thickness of the pancreas was measured at three levels (head, body, tail). Three groups of diabetic patients were examined: 20 insulin-dependent patients, 25 patients not treated with nor dependent on insulin, and 12 patients treated with but not dependent on insulin. A control group included 57 nondiabetic patients. The ages of the control subjects were similar to those of the diabetic patients. The statistical significance of the differences between groups of diabetic patients and control subjects was estimated by using Student's t test for the values of density and thickness and the chi 2-test for the prevalence of pancreatic lobulation. The density of the pancreas in diabetic patients and control subjects was not statistically different. Diabetic patients had increased lobulation of the pancreas. All parts of the pancreas tended to be smaller in diabetic patients, but the degree of reduction varied. It was modest in the patients not treated with insulin, pronounced in insulin-dependent patients, and intermediate in non-insulin-dependent, insulin-treated patients. Moreover, the size of the body was significantly reduced in all three groups, whereas the size of the pancreatic head was preserved in patients not treated with insulin. In conclusion, CT of the pancreas shows that although density in diabetic patients is normal, lobulation is increased. Reduction in size involves the body of the pancreas more than other parts of the gland and is more pronounced in insulin treated diabetic patients. CT of the pancreas might be useful to predict which diabetic patients will require insulin therapy. PMID- 1503019 TI - Diagnosis of acute appendicitis in pregnant women: value of sonography. AB - OBJECTIVE: The diagnosis of acute appendicitis in pregnant women often is difficult to make on the basis of clinical findings, and radiologic examination is limited because of the potentially hazardous effects of radiation. This study was done to assess the value of sonography in the diagnosis of acute appendicitis in pregnant women. SUBJECTS AND METHODS: We obtained sonograms in 45 pregnant women with clinically suspected acute appendicitis. Our sonographic technique included graded-compression scanning. The left lateral decubitus position was used in the third trimester of gestation. The sonographic criterion for the diagnosis of acute appendicitis was visualization of an incompressible appendix with a maximal diameter greater than 7 mm. We correlated the sonographic findings with the surgical findings in 22 cases and with the results of clinical follow-up in 23 cases. RESULTS: Sonography could not be used to make the diagnosis in three (7%) of 45 patients because the size of the gravid uterus prevented use of the graded-compression technique. These three patients were in the third trimester of pregnancy (greater than 35 weeks' gestation). Sonographic findings were used as a basis for diagnosis in 42 cases. Acute appendicitis was diagnosed on the basis of sonograms in 16 patients, and in all but one of these patients, acute appendicitis was confirmed by surgical and pathologic findings. In the 42 cases in which the imaging findings indicated the diagnosis, the overall sensitivity of sonography was 100%, the specificity was 96%, and the accuracy was 98%. CONCLUSION: Our experience suggests that graded-compression sonography is a valuable procedure for detecting acute appendicitis in pregnant women despite technical difficulty in performing it during the third trimester of pregnancy. PMID- 1503021 TI - Multiple smooth-muscle tumors of the colon and adrenal gland in an adult with AIDS. PMID- 1503020 TI - Pipestem appearance of small bowel in strongyloidiasis is not pathognomonic of fibrosis and irreversibility. PMID- 1503022 TI - Inadvertent barium hysterosalpingography. PMID- 1503023 TI - Renal diseases in patients with AIDS: sonographic findings. AB - This essay illustrates the spectrum of sonographic findings of various renal manifestations of AIDS. The most common renal abnormality in patients with AIDS is nephropathy, which is manifested by deterioration of renal function and proteinuria. Acute tubular necrosis, intrarenal infections, focal nephrocalcinosis, hydronephrosis, and neoplasms also may occur. PMID- 1503024 TI - Submucosal uterine leiomyomas: diagnosis of prolapse into the cervix and vagina based on MR imaging. AB - OBJECTIVE: We describe the MR appearance, signs and symptoms, and pathologic findings in five patients with submucosal leiomyomas that prolapsed into the cervical or vaginal canal. SUBJECTS AND METHODS: During the past 3 years, five women aged 33-53 years (mean, 43 years) were identified prospectively at MR imaging as having prolapsing uterine leiomyomas. The diagnosis was confirmed by surgical pathology. MR imaging was performed on a 1.5-T unit, using both T1- and T2-weighted spin-echo or fast spin-echo sequences. The images were analyzed for signal intensity, presence of a stalk, and caudal extent of the prolapsed leiomyoma. RESULTS: These leiomyomas, the presence of prolapse, and the caudal extent of prolapse were detected prospectively on MR images in all five cases. Prospective localization of the stalk in two cases aided subsequent hysteroscopic resection. MR imaging correctly indicated the presence of hemorrhage in one, degeneration in a second, and the absence of these complications in two others. In the fifth case, a hemorrhagic focus in the distal tip of the leiomyoma was not detected on MR images obtained 3 days before surgery. CONCLUSION: MR imaging is useful for the diagnosis and characterization of uterine leiomyomas that have prolapsed into the cervical or vaginal canal. PMID- 1503026 TI - Plural effusions. PMID- 1503025 TI - Temporomandibular joint: relationship between MR evidence of effusion and the presence of pain and disk displacement. AB - OBJECTIVE: The purpose of this study was to correlate MR evidence of joint effusion in the temporomandibular joint with symptoms of joint pain and the presence of disk displacement and arthrosis. SUBJECTS AND METHODS: The temporomandibular joints of 379 patients with clinical symptoms of temporomandibular joint disorders and 11 asymptomatic volunteers were imaged bilaterally. Sagittal and coronal proton density-weighted and T2-weighted images were obtained. Imaging findings of joint effusion were correlated with the presence of disk displacement and arthrosis and the symptom of pain. RESULTS: MR showed effusion in 7% of the joints with normal superior disk position, 40% of the joints with disk displacement with reduction, 50% of the joints with disk displacement without reduction, and 27% of the joints with arthrosis. Two of the control subjects had disk displacement with reduction; MR did not show joint effusion in any of the control subjects. A strong association was seen between joint effusion and joint pain. Joint effusion was seen in 46% of the joints on the more painful side and in 13% of the joints on the less painful side. CONCLUSION: The results show that temporomandibular joint effusions primarily occur in joints with disk displacement and are strongly associated with joint pain. PMID- 1503027 TI - Injuries of the superior portion of the glenoid labrum involving the insertion of the biceps tendon: MR imaging findings in nine cases. AB - The goal of this investigation was to describe the MR appearance of traumatic fraying or detachment of the superior portion of the glenoid labrum including the insertion of the tendon of the long head of the biceps. This condition is caused either by an acute injury or by repeated overhead motion during participation in sports. In nine patients with such a lesion, the arthroscopic report and MR images were available for review. These patients were 22-64 years old (mean, 38). In four patients only fraying was noted during arthroscopy, in four patients the superior part of the labrum was detached together with the insertion of the biceps tendon, and in one case there was a bucket-handle tear of the superior portion of the labrum. The MR images were retrospectively evaluated by three osteoradiologists in conference. Signal changes within the labrum and detachment of the labrum were noted, and the findings were compared with the results of arthroscopy. MR imaging did not allow recognition of simple fraying. In two of the five cases with arthroscopic findings of detachment of the superior labrum from the glenoid rim, differentiation between complete and partial labral detachments was not possible even with MR arthrography. However, in these cases the patient's age and history led to the correct diagnosis. We conclude that early traumatic abnormalities of the superior portion of the labrum cannot be detected with MR imaging. Complete detachment, however, can be demonstrated if the patient's age and history are taken into consideration. PMID- 1503028 TI - Value of unenhanced spin-echo MR imaging in distinguishing between synovitis and effusion of the knee. AB - OBJECTIVE: We performed a study to determine if unenhanced spin-echo MR imaging can be used to differentiate effusion from synovitis of the knee joint. MATERIALS AND METHODS: Unenhanced spin-echo MR imaging examinations of 1051 consecutive patients referred for evaluation of internal derangement of the knees were reviewed. Twelve of 550 knees with significant joint effusion also had thickened or irregular synovium. Of these, the cause of synovitis was proved in 10 patients. In the other two, the cause was unknown. RESULTS: Thickened synovium was of intermediate signal intensity on T1-weighted MR images compared with the lower signal intensity of joint effusion. In eight cases, the thickened synovium had an intermediate signal intensity on T2-weighted images relative to the high signal of the joint effusion. MR images in the other four cases showed increased signal intensity indistinguishable from that of joint effusion. CONCLUSION: Our experience suggests that unenhanced spin-echo MR images can be used to distinguish synovitis from effusion in the knee joint. PMID- 1503029 TI - Intraarticular sonography for imaging the knee menisci: evaluation in cadaveric specimens. PMID- 1503030 TI - Elastofibroma: MR and CT appearance with radiologic-pathologic correlation. AB - OBJECTIVE: The purpose of our study was to determine the MR and CT appearances of elastofibroma and correlate the imaging features with the underlying pathologic findings. MATERIALS AND METHODS: We reviewed retrospectively the MR and CT findings in five cases of elastofibroma. All patients had a soft-tissue mass; one patient also complained of pain. The mean age of the patients was 71 years (range, 63-79 years). Four lesions occurred in the subscapular region, and one occurred in the thigh. In addition, we reviewed and compared the demographic data of 72 histologically proved cases for which we had archival data. RESULTS: Three of four lesions evaluated with spin-echo MR imaging were approximately isointense with skeletal muscle and contained areas with a signal intensity similar to that of fat; these corresponded to areas of dense collagen and interspersed fat, respectively. In the fourth case, the MR appearance was nonspecific. In one case, MR imaging with gadopentetate dimeglumine showed areas with and without enhancement. Three of four lesions evaluated with CT had variable margins, with tissue attenuation similar to that of the adjacent soft tissue as well as scattered areas of decreased attenuation, suggesting fat within the lesion. In one case, the lesion was well defined and relatively homogeneous with an attenuation less than that of skeletal muscle. CONCLUSION: The MR and CT features of elastofibroma are different from those of most other soft-tissue tumors, reflecting entrapped fat within a predominantly fibrous mass. Although these features are not pathognomonic, their presence in a subscapular lesion in an older patient suggests a presumptive diagnosis of elastofibroma. PMID- 1503031 TI - Neoplastic diseases affecting the central skull base: CT and MR imaging. AB - Modern imaging techniques play a vital role in the diagnostic evaluation and follow-up of patients with neoplastic disease affecting the skull base. Many of these lesions have a high rate of recurrence if surgical removal is not complete. Newer, more aggressive surgical approaches can have a maximal effect only if the full extent of a lesion is known preoperatively. CT and MR imaging provide the surgeon with detailed information about every site of tumor involvement. Although these lesions are not common in clinical radiologic practice, the radiologist must be prepared to offer a reasonable differential diagnosis and a full evaluation of the extent of disease. This review presents some of the more commonly encountered tumors that can affect the skull base and describes their radiologic features, with emphasis on CT and MR imaging. PMID- 1503032 TI - Diffusion MR imaging: clinical applications. AB - Water self-diffusion, a recently discovered source of contrast on MR images, has already shown promise for some clinical applications. Most studies have been of the brain, essentially for technical reasons. Diffusion is useful in distinguishing the different components of brain tumors (cystic regions, edema, necrosis) from the tumor core itself. Recent studies have shown that diffusion is anisotropic in brain white matter (i.e., dependent on the fiber tract's orientation in space), offering new insights into myelin disorders. Diffusion is also dramatically altered in the minutes following ischemic injury in the cat brain, which may have tremendous impact for the diagnosis and management of hyperacute stroke. With ultrafast acquisition schemes, diffusion imaging has also been used outside the CNS, for instance, in the eye and kidney. Future applications include diffusion-localized spectroscopy and temperature imaging. This article reviews recent progress in this field and suggests potential applications. PMID- 1503033 TI - Sacral neurofibroma. PMID- 1503034 TI - Cystic masses of the head and neck: pitfalls in CT and MR interpretation. PMID- 1503035 TI - CT and MR imaging findings in adults with cerebellar medulloblastoma: comparison with findings in children. AB - The goal of this study was to determine if certain imaging features suggest the diagnosis of cerebellar medulloblastoma in adults and to determine how often the classic CT appearance seen in children is present in adults. The study included 28 adult patients with proved cerebellar medulloblastoma. The tumor was located in the cerebellar vermis in 14 patients and in a cerebellar hemisphere in 14 patients. Thirteen patients had unenhanced CT of the brain, all patients had contrast-enhanced CT, and eight patients had unenhanced MR imaging. The imaging features in adults were compared with those in children, as described in the literature. In our adult patients, all tumors were hyperdense compared with gray matter on unenhanced CT and showed a slight to moderate increase in density after injection of contrast medium. Thirteen lesions had well-defined margins, and 15 had poorly defined margins. Low-density areas consistent with cystic and necrotic degeneration were detected in 23 (82%) of the 28 tumors. By comparison, in children, medulloblastoma usually originates in the vermis. As in adults, the mass is hyperdense on unenhanced CT, but enhances markedly and homogeneously after injection of contrast medium. Usually no evidence of cyst formation or necrosis is seen, and the tumor margins are well defined. This classic CT appearance of medulloblastoma in children was identified in only three (11%) of the 28 adult patients. Medulloblastoma has a variable MR appearance in both children and adults. On T2-weighted images, lesions are hypo-, iso-, or hyperintense compared with normal gray matter. The CT findings of medulloblastoma in adults usually differ from those of medulloblastoma in children. The tumor has a variable and nonspecific appearance in adults and should always be considered in the differential diagnosis of a mass in the posterior fossa. PMID- 1503036 TI - Tortuous vertebral artery shown by MR and CT. PMID- 1503037 TI - Diagnosis of liver disease in children: value of MR angiography. AB - We retrospectively studied the clinical use of MR angiography, a gradient-echo technique susceptible to motion, in the preoperative evaluation of the hepatic vasculature in children with liver disease. Twenty imaging examinations were performed in 18 patients 3 months to 10 years old (mean, 2.3 years). Eleven patients had liver tumors and seven had cirrhosis associated with biliary atresia, cystic fibrosis, and short-bowel syndrome. Respiratory motion artifacts were present in most patients, but all MR angiographic studies were technically adequate. Comparing MR angiograms with spin-echo images, we found that vascular visualization was better with MR angiography in 12 cases (60%), equal in five (25%), and worse in three (15%). In 10 of 20 cases, MR angiography provided additional vascular information not present on spin-echo images. MR angiography is a useful adjunct to spin-echo imaging for assessing hepatic vascular anatomy in children with liver disease. PMID- 1503038 TI - Neonatal hemochromatosis: diagnosis with MR imaging. PMID- 1503039 TI - AIDS-related cholangitis in children: sonographic findings. PMID- 1503040 TI - Bile nephrosis in a neonate: sonographic findings of rapid kidney enlargement and increased echogenicity. PMID- 1503041 TI - Strategies for improving power in diagnostic radiology research. AB - Research studies in diagnostic radiology often compare the diagnostic abilities of two imaging techniques. The "power" of such studies is the probability that they will detect a difference in abilities of a certain amount when, indeed, such a difference does exist. This article outlines several strategies that can be used to assess and improve the power of radiologic diagnostic studies. These strategies include selection of cases and controls, matching, use of one-tailed tests, selection of significance level, and choice of sample size. PMID- 1503042 TI - The Society of Cardiovascular and Interventional Radiology: 17th annual scientific meeting, April 1992. PMID- 1503043 TI - American Roentgen Ray Society, 92nd annual meeting, May 1992. PMID- 1503044 TI - A small cloud on the horizon. PMID- 1503045 TI - Diagnosis of intrathoracic goiter based on sonographic findings. PMID- 1503046 TI - Bronchiolitis obliterans with organizing pneumonia: atypical appearance on radiographs. PMID- 1503047 TI - Aortopulmonary fistula detected by CT. PMID- 1503048 TI - Motion artifact simulating aortic dissection on CT. PMID- 1503049 TI - Choledochal cysts: classification and cholangiographic appearance. PMID- 1503050 TI - Benign schwannoma of the pancreas. PMID- 1503051 TI - Stress-induced adrenal hyperplasia simulating metastatic disease: CT and MR findings. PMID- 1503052 TI - Metastatic papillary adenocarcinoma to the brain simulating toxoplasmosis on CT in a patient with AIDS. PMID- 1503053 TI - Tuberculosis involving the patella. PMID- 1503054 TI - Psychogenic urinary retention in a child. PMID- 1503055 TI - Relationships between upper-arm anthropometry and soft-tissue composition in postmenopausal women. AB - The value of upper-arm anthropometry as a measure of lean- and fat-tissue masses in 140 normal postmenopausal white women was assessed by studying the relationships of these measures to total and regional fat, and lean masses measured by dual-energy x-ray absorptiometry. Midarm circumference (MAC) was highly correlated with total and regional fat masses (r = 0.85-0.89, P less than 0.0001) but less so with lean-tissue masses (r = 0.26-0.34). Triceps-skinfold thickness was also correlated with fat masses (r = 0.70-0.74, P less than 0.0001) but not with lean mass (r = 0.02-0.09). The derived index, arm muscle area (AMA), was less closely correlated with fat mass than was MAC (r = 0.59-0.61), but its correlation with lean-tissue mass was comparable to that for MAC (r = 0.37-0.43). Multiple-regression analysis confirmed that the anthropometric indices were more closely correlated with fat than with lean mass. It is concluded that all these indices are useful measures of fat mass but that none, including AMA, is a specific index of lean-tissue mass in normal postmenopausal women. PMID- 1503056 TI - Reduced tissue arachidonic acid concentration with chronic ethanol feeding in miniature pigs. AB - The effect of ethanol feeding on the essential fatty acid content of tissues has been contradictory. To define the effect, we analyzed fatty acid profiles in various tissues from five miniature pigs fed daily 105 kJ basal diet/kg body wt and 146 kJ ethanol/kg body wt, and also five control pigs pair-fed the same amount of basal diet but with corn starch substituted for ethanol. After 12 mo, biopsy samples were taken, and tissue fatty acid profiles were analyzed. In the phospholipid fraction from the ethanol group there was a uniform decrease in arachidonic acid (AA) and an increase in oleic acid in liver, serum, and muscle. AA was consistently decreased in the triglyceride fractions of liver, serum and subcutaneous adipose of the ethanol group. Possible explanations for this general reduction in tissue AA with ethanol feeding include decreased activities of delta 6 and delta 5 desaturases, and a displacement of AA from lipid fractions by other fatty acids. PMID- 1503057 TI - Relationships between 3-y longitudinal changes in body mass index, waist-to-hip ratio, and metabolic variables in an active French female population. AB - Three-year longitudinal changes in body mass index (BMI), waist-to-hip ratio (WHR), and metabolic variables were examined in 209 active French women. For the entire group, a weak but significant positive association was found between change in BMI and change in WHR. However, analysis of covariance according to the degree of abdominal fat distribution showed a heterogeneity of this association that was confined to women with abdominal fat distribution. Changes in BMI were positively associated with changes in total cholesterol (P less than 0.05), triglycerides (P less than 0.10), and blood pressure (P less than 0.001), whereas changes in WHR were associated with changes in triglycerides (P less than 0.05) and diastolic blood pressure (P less than 0.10). These longitudinal results suggest that a more favorable body-fat pattern and metabolic profile might be achieved by reducing weight, or at least by preventing weight gain, particularly in women with high abdominal-fat distribution. PMID- 1503058 TI - Massive overfeeding and energy balance in men: the Guru Walla model. AB - To determine the magnitude of the thermogenic response to a massive long-term overfeeding, an energy-balance study was carried out in nine lean, young Cameroonian men participating in a traditional fattening session: the Guru Walla. Food intake, body weight, body composition, activity, and metabolic rates were recorded during a 10-d baseline period and over the 61-65 d of fattening. Total energy expenditure (TEE) was measured by using doubly labeled water during the baseline period and the final 10 d of Guru Walla. Cumulative overfeeding consisted of 955 +/- 252 MJ (chi +/- SD) mainly as carbohydrate. Body-weight increase was 17 +/- 4 kg, 64-75% as fat. Metabolic rates increased but TEE did not. However, when accounting for the reduction in physical activity, substantial thermogenesis was observed but its amplitude was not greater than that observed under less extreme carbohydrate-overfeeding conditions. If luxuskonsumption does exist, it is not related to the magnitude of the cumulative overfeeding. PMID- 1503059 TI - Effect of a zinc-fortified formula on immunocompetence and growth of malnourished infants. AB - This study attempted to define the possible contribution of zinc nutrition to immunocompetence and growth in severely malnourished infants. The effect of zinc supplementation was evaluated in marasmic infants during nutritional rehabilitation by using a controlled double-blind design in which 19 infants fed a zinc-fortified formula were compared with 20 infants fed the same non supplemented formula. Evaluation of immunocompetence, growth, and zinc, copper, and iron status was performed on admission and at 30, 60, and 105 d of nutritional rehabilitation. Although energy intake was similar in both groups, the zinc-supplemented infants had significantly higher linear growth gain, and their immune function improved as demonstrated by conversion of their delayed hypersensitivity skin reactions, enhanced lymphoproliferative response to PHA, and increased salivary IgA concentrations. Thus, the use of a zinc-fortified formula during nutritional rehabilitation can prevent the development of zinc deficiency and improve growth and immune function. PMID- 1503060 TI - Protein-energy requirements of boys 12-14 y old determined by using the nitrogen balance response to a mixed-protein diet. AB - Short-term nitrogen-balance response to graded intakes of a vegetable mixed protein diet and to a milk-egg protein diet was tested in eight healthy male children aged 12-14 y. They received 72, 104, 136, and 168 mg N.kg body wt-1.d-1 for 10 d while on the mixed diet, and 160 mg N.kg-1.d-1 on the milk-egg diet. The mean regression equation was nitrogen balance = 0.64 (nitrogen intake)-74, all values are in mg N.kg-1.d-1. Apparent digestibility was 86% and 85% for the mixed and milk-egg diets when the subjects received 168 and 160 mg N.kg-1.d-1, respectively. Mean nitrogen intake for satisfactory nitrogen retention for growth on the mixed diet was 147 mg N.kg-1.d-1; the recommended protein allowance to cover 97.5% of the population, which was derived by using a CV of 12.5%, is 1.15 g protein.kg-1.d-1. We conclude that FAO/WHO/UNU recommendations are adequate, at least for short-term nitrogen retention; long-term studies are needed to evaluate the chronic safety of this protein allowance. PMID- 1503061 TI - Morbidity and the growth of stunted and nonstunted children, and the effect of supplementation. AB - Children aged 9-24 mo were recruited by a survey of poor areas of Kingston, Jamaica. Stunted children were randomly assigned to supplementation or not. Weekly morbidity histories were taken for 2 y. Separate multiple regressions on each symptom for weight or length gain in 2-mo intervals showed significant reductions in weight gain with coughing, apathy, anorexia, diarrhea, and fever, ranging from -2.1 to -16.8 g/d ill. Apathy and diarrhea reduced gains in length ( 0.26 and -0.20 mm/d ill). Significant reductions in linear growth with lower respiratory-tract infections (-0.16 mm/d ill) occurred only in nonsupplemented children. Growth over 4-mo intervals was reduced if diarrhea occurred in the first 2 mo of the interval but there were no long-term effects of apathy, fever, or anorexia. Some of the effects of morbidity on growth were therefore transient and morbidity is unlikely to be a major cause of growth retardation in this population. PMID- 1503062 TI - Effects of dietary cholesterol, type of fat, and sex on bile lipid composition of adult baboons. AB - We measured the effects of dietary cholesterol (0.24 vs 0.0024 mg/kJ), type of dietary fat [saturated, a ratio of polyunsaturated to saturated fatty acids (P:S) of 0.37, vs unsaturated (P:S of 2.2)], and sex on biliary lipid and bile acid conjugate composition of 80 adult pedigreed baboons. From these data we calculated the bile cholesterol saturation index and the bile acid hydrophobicity index. Dietary cholesterol significantly increased the bile cholesterol concentration by 25% and the bile cholesterol saturation index by 15%, but did not significantly affect the bile acid conjugate composition or the bile acid hydrophobicity index. Diets high in saturated fatty acid compared with unsaturated fatty acid significantly decreased the bile cholesterol concentrations by 26% and the saturation index by 23%. Saturated fatty acid also decreased the proportion of hydrophobic bile acids and lowered the bile hydrophobicity index. Male baboons had a higher cholesterol saturation index and a lower hydrophobicity index than females. Dietary cholesterol and saturated fatty acid independently influence the bile lipid composition and the cholesterol saturation index. PMID- 1503063 TI - Phenylalanine and tyrosine kinetics in relation to altered protein and phenylalanine and tyrosine intakes in healthy young men. AB - Plasma phenylalanine (Phe) and tyrosine (Tyr) turnover and the rate of conversion of phenylalanine to tyrosine (Phehyd) and of phenylalanine oxidation (Pheox) after reduced intakes of Phe and Tyr were determined in a metabolic study involving five healthy young adult men. In a pilot study, six postabsorptive young men received either 12- or 4-h infusions of [2H2]Phe and [1-13C]Tyr or [1 13C]Phe and [2H2]Tyro. From these results a primed 8-h constant infusion of [1 13C]Phe and [2H2]Tyr and [2H3]leucine was used in the metabolic study (first 3 h fasted, the 5 h fed) at the end of 1-wk periods during which subjects received an adequate nitrogen L-amino acid based-diet followed by a restricted intake of Phe and Tyr. This procedure was again repeated after 1 and 3 wk when subjects were given a diet low in both nitrogen and Phe and Tyr. Phe and Tyr fluxes were not significantly affected by diet during the fasted metabolic state but Tyr fluxes were lower when the restricted intakes were given. Compared with the rate during the fasting state, Pheox was significantly higher (P less than 0.01) when the adequate diet was consumed; Pheox and Phehyd for fed and fasted states were similar when Phe and Tyr were restricted. PMID- 1503064 TI - Riboflavin requirements and exercise adaptation in older women. AB - The effects of exercise training on riboflavin requirements and of riboflavin intake on endurance were examined in 14 women, 50-67 y of age, who participated in a 10-wk, two-period crossover exercise study at two riboflavin intakes, 0.15 micrograms/kJ (0.6 micrograms/kcal) and 0.22 micrograms/kJ (0.9 micrograms/kcal). Subjects exercised 20-25 min/d, 6 d/wk, for 4-wk periods on a cycle ergometer at 75-85% of their maximal heart rate. Riboflavin status was assessed by measuring the erythrocyte glutathione reductase activity coefficient (EGRAC) and urinary riboflavin excretion. Physical performance was evaluated by using a walking treadmill test to determine maximal oxygen capacity (VO2max) and anaerobic threshold by gas exchange (ATGE). Exercise significantly affected riboflavin status as EGRAC increased (P less than 0.001) and riboflavin excretion decreased (P less than 0.01) in both groups. VO2max increased significantly with exercise (P less than 0.01). However, changes in VO2max (L/min) and ATGE with exercise training were not different in the two groups. Riboflavin requirements of older women increased with exercise training, but increased riboflavin intake did not enhance improvements in endurance. PMID- 1503065 TI - Effect of iron on serum 25-hydroxyvitamin D and 24,25-dihydroxyvitamin D concentrations. AB - In 13 of 17 infants (aged 10.5 +/- 4.3; mean +/- SD mo) with iron-deficiency anemia, the serum 24,25-dihydroxyvitamin D concentration was below the normal range and in 9 of these 13 the serum 25-hydroxyvitamin D concentration was below the normal range despite the fact that these infants received 10 micrograms vitamin D/d from the age of 1 mo. The infants were treated with intramuscular iron dextran (Imferon). The iron-dextran treatment increased the hemoglobin and serum iron concentrations as well as 25-hydroxyvitamin D and 24,25 dihydroxyvitamin D concentrations. It is known that iron deficiency impairs fat and vitamin A intestinal absorption. Therefore, it is suggested that absorption of vitamin D may also be impaired. This may contribute to the development of vitamin D deficiency. Iron supplementation may have improved the absorption of vitamin D in the small intestine and hence increased the vitamin D concentration in the plasma. PMID- 1503066 TI - Serum 25-hydroxyvitamin D: distribution and determinants in the Swiss population. AB - The serum 25-hydroxyvitamin D [25(OH)D] concentration was measured in a representative sample of the general adult population in Switzerland (n = 3276). The median concentration was 46 nmol/L and no significant difference was found between men and women. Between the ages of 25 and 74 y, 25(OH)D was not significantly correlated with age (r2 = 0.01). Six percent of the population was vitamin D deficient [ie, 25(OH)D less than or equal to 20 nmol/L] and between 34% and 95% had a relatively low concentration of vitamin D (ie, less than 38 or less than 95 nmol/L, respectively). Among the determinants of low 25(OH)D were indicators of little sunshine exposure, such as the winter season [odds ratio (OR) 2.4, 1.5-3.7 (95% confidence interval)] and less than 30 min of time spent outdoors daily by individuals greater than 65 y of age (OR 5.6, 1.5-21.2), as well as indicators of low nutritional intake of vitamin D, such as the absence of regular intake of butter or margarine (OR 2.0, 1.3-3.1) and the consumption of few dairy products (OR 1.7, 1.2-2.4). PMID- 1503067 TI - Studies on the application of the relative-dose-response test for assessing vitamin A status in older adults. AB - We investigated the time course and the reproducibility of the relative-dose response (RDR) test for assessing vitamin A status in older adults. The maximum plasma retinol response to 480 retinol equivalents (RE) of retinyl palmitate in abnormal responses was at 6 or 7 h after dosing compared with the 5-h sampling interval recommended by others for younger adults and children. With respect to reproducibility, the diagnostic concordance of two RDR tests at 7-d intervals in 14 elders was 71%. In 29% of tests, one test was abnormal and the other normal. Linear regression of the two RDR values in these 14 subjects gave a correlation coefficient of -0.08. We conclude that the procedure for the RDR should be modified when applied to persons greater than 60 y of age, and that multiple repetitions of the test are needed to provide a stable indication of vitamin A stores in an elderly individual. PMID- 1503068 TI - Vitamin B-6 status of breast-fed neonates: influence of pyridoxine supplementation on mothers and neonates. AB - Vitamin B-6 concentrations in human milk are known to respond rapidly to changes in maternal vitamin B-6 intake. In this study, mothers were supplemented during the first 28 d of lactation with 2 or 27 mg pyridoxine (PN)-HCl/d and a subgroup of breast-fed infants of the 2-mg/d-supplemented mothers were supplemented with 0.4 mg PN-HCl/d. Vitamin B-6 intakes of breast-fed infants reflected the amount of their mother's supplement; intakes were highest for the vitamin-supplemented infants. Vitamin B-6 intake of mothers was a strong indicator of infant vitamin B 6 status. Vitamin intake of infants correlated significantly with five measures of vitamin B-6 status. Plasma pyridoxal-5'-phosphate (PLP) concentrations and birth weight were the strongest predictors of infant growth that were examined. Alkaline phosphatase activity in the mother's milk and infant plasma reflected pyridoxal-PLP ratios in these fluids, suggesting that the enzyme acts in regulating circulating vitamer concentrations. PMID- 1503069 TI - Concentrations of the water-soluble vitamins thiamin, ascorbic acid, and folic acid in serum and cerebrospinal fluid of healthy individuals. AB - Thiamin, thiamin monophosphate, ascorbic acid, and folic acid were determined in serum and cerebrospinal fluid (CSF) in 31 outpatients who underwent a myelography because of back-pain. All subjects were otherwise healthy. The CSF concentration (mean +/- SD) was 8.6 +/- 3.9 nmol thiamin/L, 16.9 +/- 8.3 nmol thiamin monophosphate/L, 133 +/- 58.8 mumol ascorbic acid/L, and 44.9 +/- 13.2 nmol folic acid/L. The CSF-serum ratio was 2.1 +/- 0.8 for thiamin, 8.3 +/- 4.3 for thiamin monophosphate, 3.0 +/- 1.4 for ascorbic acid, and 3.3 +/- 0.8 for folic acid; the amount in CSF was significantly higher than in serum for each compound. These results support the existence of a saturated transport mechanism of water-soluble vitamins from serum into CSF for thiamin monophosphate, ascorbic acid, and folic acid. However, low CSF concentrations are correlated with low serum concentrations for the three vitamins. High serum concentrations should therefore be advocated to ensure high CSF concentrations. PMID- 1503070 TI - Estimated mineral intakes of toddlers: predicted prevalence of inadequacy in village populations in Egypt, Kenya, and Mexico. AB - Intakes of minerals and factors that might affect their bioavailability were estimated for 255 toddlers aged 18-30 mo living in villages in Egypt, Kenya, and Mexico. Mean intakes over 1 y were compared with international-requirement estimates by using a probability approach. The prevalence of iron intakes likely to be inadequate to prevent anemia was estimated as 35% in Egypt, 13% in Kenya, and 43% in Mexico. The prevalence of zinc intakes likely to be inadequate to meet basal requirements was estimated as 57% and 25% in Kenya and Mexico, respectively, but only 10% in Egypt, where the use of yeast-leavened breads was judged to have improved zinc availability. There was no suggestion that estimated copper or magnesium intakes were inadequate, but calcium intakes in Kenya and Egypt were well below recommended amounts. Studies of factors affecting mineral bioavailability in the diets of these countries' populations could suggest dietary changes that might improve effective mineral intake with minimal cost. PMID- 1503071 TI - Soy protein, phytate, and iron absorption in humans. AB - The effect of reducing the phytate in soy-protein isolates on nonheme-iron absorption was examined in 32 human subjects. Iron absorption was measured by using an extrinsic radioiron label in liquid-formula meals containing hydrolyzed corn starch, corn oil, and either egg white or one of a series of soy-protein isolates with different phytate contents. Iron absorption increased four- to fivefold when phytic acid was reduced from its native amount of 4.9-8.4 to less than 0.01 mg/g of isolate. Even relatively small quantities of residual phytate were strongly inhibitory and phytic acid had to be reduced to less than 0.3 mg/g of isolate (corresponding to less than 10 mg phytic acid/meal) before a meaningful increase in iron absorption was observed. However, even after removal of virtually all the phytic acid, iron absorption from the soy-protein meal was still only half that of the egg white control. It is concluded that phytic acid is a major inhibitory factor of iron absorption in soy-protein isolates but that other factors contribute to the poor bioavailability of iron from these products. PMID- 1503072 TI - Factors affecting bone density in young adults. AB - A 14-y follow-up of 581 children who took part in a randomized controlled trial of the effect of a milk supplement on growth of children was conducted to investigate the supplement's effect on adult bone mineral content (BMC) and density (BMD). BMC and BMD of the nondominant forearm were measured by single photon absorptiometry in 371 subjects (64%) aged 20-23 y, at a proximal site (shaft of radius and ulna) and at a distal site near the wrist. BMCs and BMDs tended to be higher in the intervention group (NS). Cross-sectionally, BMD was positively associated with body weight (P less than 0.01) in both sexes; inversely associated with alcohol consumption (P less than 0.05), and positively with manual occupation (NS) in men; positively associated with current intakes of calcium (P less than 0.05), vitamin D (P less than 0.01), and sports activity during adolescence (P less than 0.01), and inversely with parity (NS) in women. In multiple linear-regression analysis body weight and sports activity during adolescence were stronger determinants of female BMD than was diet. PMID- 1503073 TI - Optimal daytime feeding regimen to prevent postprandial hypoglycemia in type 1 glycogen storage disease. AB - To determine the optimal daytime dietary regimen for type 1 glycogen storage disease (GSD), we used uncooked cornstarch (UCS) at a basal glucose production rate (GPR) in single and divided doses, with mixed meals at 0700 and 1700 h. This regimen was compared with a 1.5 times larger single dose of UCS at 0700 h, and with dextrose at GPR at 1200 h. Two-hour UCS loads (amount equal to GPR in 2 h) given with a mixed meal at 0700 h and 180 min later maintained mean blood glucose (BG) concentrations at greater than or equal to 4.2 mmol/L for 300 min. BG was significantly greater from 240 to 300 min compared with a single 4-h UCS load, and at 300 min compared with a single 6-h UCS load. Similar effects were noted when the divided UCS regimen was given with a mixed meal at 1700 h, but not when isoenergetic amounts of dextrose were given on the same schedules with a mixed meal at 1200 h. A daytime schedule of six UCS feedings (with the three main meals and 180 min later) at GPR maintains BG at concentrations that should minimize biochemical abnormalities and optimize clinical outcome in patients with GSD. PMID- 1503074 TI - Parent-child relationships in nutrient intake: the Framingham Children's Study. AB - Nutrient intake affects many of the identified risk factors for coronary heart disease (CHD). Although CHD risk factors have been shown to aggregate within families, less is known about the familial aggregation of nutrient intake. We analyzed diet records for an average of 9 d per subject on 87 mothers, 83 fathers, and 91 children aged 3-5 y. A statistically significant but modest correlation (r less than 0.50) was found between parents' and children's intakes for most nutrients. The intake of nutrients was more strongly related between mothers and children than between fathers and children, and there was a stronger association with children's values for parents consuming more meals at home. The results of this study confirm that parents' eating habits have an impact on the nutrient intake of their preschool children; the study furnishes indirect support for dietary-intervention programs targeting families for the primary prevention of CHD. PMID- 1503075 TI - Decaffeinated coffee and serum LDL-cholesterol concentrations. PMID- 1503076 TI - Coffee and lipoprotein cholesterol. PMID- 1503077 TI - Overestimation of vitamin C status because of the erythorbic acid content of foods. PMID- 1503078 TI - Anticancer effects of phytate. PMID- 1503079 TI - Human resting energy expenditure in relation to dietary potassium. PMID- 1503080 TI - Effect of interleukin-1, tumor necrosis factor-alpha, and interferon-alpha on the blast cells of acute myeloblastic leukemia. AB - In this study, we further established the role of interleukin-1 alpha (IL-1 alpha), interleukin-1 beta, tumor necrosis factor-alpha (TNF-alpha), and interferon-alpha (IFN-alpha) as regulators of proliferation of acute myeloid leukemia (AML) cells. AML cells from 8 of 15 patients incorporated high levels of 3H-thymidine (3H-TdR) in the absence of exogenous growth factors. The spontaneous DNA synthesis could be abrogated with monospecific antibodies directed toward IL 1 alpha, IL-1 beta, or TNF-alpha, as well as with antigranulocyte-macrophage colony-stimulating factor (GM-CSF). Human recombinant GM-CSF reversed the inhibitory action of each of these antibodies and reinduced DNA synthesis in AML cells. Thus, in these cases, constitutively produced IL-1 or TNF-alpha had stimulated the synthesis of GM-CSF, which resulted in GM-CSF-dependent proliferation of AML blasts. Exogenous IL-1 up-regulated the endogenous production of GM-CSF, suggesting a positive regulation of autocrine growth factor production. We also present evidence that TNF-alpha may exert both stimulative as well as inhibitory effects on DNA synthesis in AML cells. The enhancing effect of TNF-alpha was mediated through the induction of GM-CSF production, as stimulation of DNA synthesis in AML blasts could be abrogated with anti-GM-CSF antibody. A concentration-dependent inhibitory effect of TNF-alpha on 3H-TdR incorporation into AML blasts was observed only when these cells were grown in the absence of GM-CSF. Finally, we show that human recombinant IFN-alpha is a potent inhibitor of AML cell proliferation in vitro. PMID- 1503081 TI - Regulation of transferrin receptors by iron in human erythroblasts. AB - We investigated the regulatory mechanism of human erythroblast transferrin receptors (Tf.R) under conditions of iron deprivation and iron loading. Treatment of erythroblasts with an iron chelator, desferrioxamine, induced an increase in surface Tf.R number associated with an elevation of biosynthetic rate and the mRNA level of Tf.R. Reduced cellular iron pool increased the Tf.R number by altering the level of mRNA, as in nonhemoglobin-producing cells. Although treatment of erythroblasts with hemin induced a decrease in the biosynthetic rate and in the level of mRNA, the number of surface Tf.R did not decrease. This phenomenon may explain the fact that a high level of serum iron has no influence on the surface Tf.R number in vivo, as we reported previously. We suggest the existence of a regulatory mechanism specific for hemoglobin-producing cells that keeps surface Tf.R expression constant despite iron loading. PMID- 1503082 TI - Effects of normal and sickle erythrocytes on prostacyclin release by perfused human umbilical cord veins. AB - We compared the effects of normal (AA) and sickle (SS) erythrocytes (RBC) on endothelial cell release of prostacyclin by perfused human umbilical cord veins. Two equal-length segments of fresh umbilical cords were perfused first with serum free Dulbecco's modified Eagle's medium (DMEM) to establish the basal prostacyclin production rate for each segment; then one segment was perfused with SS RBC and/or plasma, while the other segment was simultaneously perfused with AA RBC and/or plasma. Aliquots of perfusate were removed at intervals for measurement of the stable prostacyclin metabolite 6-keto-prostaglandin F1 alpha (6-keto-PGF). Basal prostacyclin production by segments from the same cord was very similar, but it varied considerably among segments from different cords. Therefore, the ratio of prostacyclin release with RBC and/or plasma to basal prostacyclin release for each segment was used to compare prostacyclin release among segments from different cords. Mean prostacyclin release was significantly higher from segments perfused with SS RBC in autologous plasma than from segments perfused with AA RBC in autologous plasma at 15, 30, and 60 min. However, no significant differences in mean prostacyclin production were observed between segments perfused with SS vs. AA RBC in DMEM or between segments perfused with SS vs. AA plasma alone. No significant correlations were observed between prostacyclin production and either the viscosity of SS and AA RBC in autologous plasma or DMEM or the adhesiveness of SS and AA RBC to cultured human umbilical vein endothelial cells. We conclude that SS RBC in autologous plasma cause increased prostacyclin release from perfused human umbilical cord veins. The perfused human umbilical cord vein system may be a useful model for comparing the response of vascular endothelium to SS and AA RBC and plasma under controlled flow conditions. PMID- 1503083 TI - Relationship of thrombohemorrhagic complications to endothelial cell function in patients with chronic myeloproliferative disorders. AB - Thrombotic and hemorrhagic disorders are common complications of the myeloproliferative disorders. Endothelial cells release both procoagulant and profibrinolytic factors, which may contribute to these hemorrhagic or thrombotic complications. The pre- and postvenous stasis levels of the procoagulant and profibrinolytic factors produced by endothelial cells were correlated with the occurrence of complications in polycythemia rubra vera (PRV) patients (n = 29) and essential thrombocythemia (ET) patients (n = 17) compared with normal patients (n = 17). Tissue plasminogen activator (tPA) activity, plasminogen activator inhibitor (PAI) activity, von Willebrand's factor (vWF) activity and antigen (vWF:Ag), and factor VIII activity were measured. The resting tPA activity was significantly higher in the two disease groups compared with normal controls, but no difference between the levels of tPA and either complication within the disease groups was observed. Significantly elevated tPA following venous stasis was observed in the patients of both disease groups who had bleeding complications. Significant decreases, compared with the normal group, in both resting and postvenous stasis levels of PAI were observed in the disease groups regardless of complication history. The subjects from both disease groups with thrombotic complications had significantly elevated resting vWF and both resting and postvenous stasis vWF:Ag levels compared with normal controls. The endothelial cell is likely to be responding to abnormal hemostasis rather than being primarily involved in the genesis of a hyper- or hypocoaguable state. PMID- 1503084 TI - Enhanced platelet reactivity and hypercoagulability in the steady state of sickle cell anaemia. AB - A prospective controlled study was undertaken to investigate the haemostatic and coagulation status of 18 adult subjects in the steady state of sickle cell anaemia (SCA), using a relatively new in vitro technique. Shear induced haemostasis, whole blood dynamic coagulation, and spontaneous thrombolysis were measured using nonanticoagulated blood. As expected, the haemoglobin levels were significantly lower and platelet counts significantly higher in subjects with SCA compared with controls. Haemostasis and coagulation were significantly enhanced in SCA. No correlation was found between the raised platelet count and enhanced haemostasis or the reduced haemoglobin and hypercoagulation, respectively. Hyperactivity of the haemostatic system may have a pathogenic role in vaso occlusive microthrombotic events and in the leg ulcers, both of which occur frequently in SCA. PMID- 1503085 TI - New variant of cytochrome b5 reductase deficiency (b5RKurashiki) in red cells, platelets, lymphocytes, and cultured fibroblasts with congenital methemoglobinemia, mental and neurological retardation, and skeletal anomalies. AB - A Japanese man with cytochrome b5 reductase (b5R) deficiency in various blood cell lineages (red cells, platelets, and lymphocytes) and in cultured fibroblasts demonstrated congenital methemoglobinemia associated with mental and neurological retardation, and various skeletal anomalies, such as spondylosis deformans and finger joint deformations, which have never been described in association with this enzyme deficiency. Cytochrome b5 reductase deficiency was most severe in red cells (0.3-4%) and less marked in platelets (13-27%), lymphocytes (18-31%), and fibroblasts (50%). The present case appears to be a new variant of cytochrome b5 reductase deficiency (b5RKurashiki). PMID- 1503086 TI - Spanish Rhnull family caused by a silent Rh gene: hematological, serological, and biochemical studies. AB - Another example of rare red cells that failed to react with all anti-Rh and anti LW antibodies was discovered in a Spanish woman suffering from a severe hemolytic anemia typical of the Rhnull syndrome. Family study and Rh blood typings demonstrated clearly that the proposita was homozygous for a silent Rh gene complex (Rhnull of the amorph type) that she inherited from her parents who are first cousins. Western blot analysis carried out with glycosylation-independent antibodies directed against the Rh polypeptide and the LW glycoprotein, respectively, confirmed that these protein components were absent from the red cells of the proposita. In addition, the patient was typed U-positive, again in agreement with the presence on her red cells of 45-75 kDa glycoproteins detected with the murine monoclonal antibody 2D10. PMID- 1503087 TI - Presence of an African beta-globin gene cluster haplotype in normal chromosomes in Sicily. AB - African admixture in Sicily has been long suspected because of the presence of the sickle gene. Nevertheless, the degree of African admixture cannot be derived from the study of HbS frequency, since this gene was most likely expanded by the selective pressure of malaria, for a long time endemic to the region. We have examined 142 individuals from the Sicilian town of Butera (12% sickle trait) to search for other markers of the globin gene cluster less likely to be selected for by malaria. The TaqI polymorphism in the intervening sequences between the two gamma genes is informative. We have found only two instances of this African marker (TaqI(-)) among 267 normal chromosomes, demonstrating that the admixture occurred at a much lower level than previously thought. PMID- 1503088 TI - Spontaneous remission in adult-onset cyclic neutropenia. PMID- 1503089 TI - Slide test for determining plasma fibrinogen level approximately. PMID- 1503090 TI - Myelomonocytic associated antigens in early B-chronic lymphocytic leukemia correlate with disease activity. PMID- 1503091 TI - Uric acid nephropathy after radiation therapy in a patient with chronic lymphocytic leukemia. PMID- 1503092 TI - Congenital combined deficiency of factor V and factor VIII with acquired ichthyosis, epidermodysplasia verruciformis, and immunological abnormalities. PMID- 1503093 TI - Myelodysplastic syndromes and malignant solid tumors: analysis of 21 cases. AB - We studied the association between myelodysplastic syndromes (MDS) and malignancies in a cohort of 155 patients with MDS, 21 of whom presented malignant solid tumors. Myelodysplasia was present after the diagnosis of cancer in eight patients (interval between the diagnosis of both conditions 18 months, median survival 49.5 months), simultaneously with diagnosis in 11 (median survival 8 months), and before malignancy in two patients (interval between the diagnosis of both conditions 47 and 7 months). One patient was given chemotherapy for lung cancer, and three patients received radiotherapy for adenocarcinoma of the kidney and cancer of the prostate. At the time of diagnosis of MDS, nine patients already presented metastatic spread. Fourteen patients died, ten as a result of tumor-related complications and four because of transformation to acute nonlymphocytic leukemia. The analysis of the incidence of malignancy in patients with MDS was statistically significant for males, and the relative risk was significant in both sexes. The results of this study show that MDS patients present a higher incidence of malignant tumors than the general population, that MDS may be of real paraneoplastic significance, and that the occurrence of MDS in cancer patients may be considered to be related to the malignancy rather than an independent phenomenon. PMID- 1503094 TI - Splenectomy vs. alpha interferon: a randomized study in patients with previously untreated hairy cell leukemia. AB - Twenty patients with previously untreated hairy cell leukemia were randomized to undergo either splenectomy or to receive interferon alfa-N1, a highly purified natural alpha interferon, as primary therapy. A response in the peripheral blood elements to a hemoglobin greater than 110 gm/l, a granulocyte count greater than 1 x 10(9)/l, and a platelet count greater than 100 x 10(9)/l (Catovsky criteria) was noted in all ten patients receiving alpha interferon but in only three of the patients undergoing splenectomy (P = less than .01). Median time to response was longer in the ten interferon patients (153 days) than in the three splenectomy responders (20 days). Median time to treatment failure was significantly greater in the alpha interferon patients (greater than 18 months) than in the splenectomy patients (less than 1 month). Survival was no different since patients relapsing following splenectomy subsequently responded to alpha interferon. A significant decrease in leukemic bone marrow infiltration was observed in seven of ten patients receiving alpha interferon and in none of the patients undergoing splenectomy. Side effects, primarily infections, were more frequent in patients receiving interferon. Alpha interferon is preferable to splenectomy as initial treatment for hairy cell leukemia. PMID- 1503095 TI - Epidemiology of AIDS in females with hemophilia and other chronic bleeding disorders in the United States: comparisons with males with chronic bleeding disorders and AIDS and with nonhemophilic female blood-transfusion recipients with AIDS. AB - From January 1, 1981 through June 30, 1990, 32 females with chronic bleeding disorders were diagnosed with acquired immunodeficiency syndrome (AIDS) in the United States. Most (81.3%) were white and greater than or equal to 30 years of age, with a median age of 37.5 years. Eighteen (56.3%) had von Willebrand's disease. Pneumocystis carinii pneumonia was reported for 16 (50%). None had Kaposi sarcoma. The median survival time was 10.8 months, with a cumulative probability of survival at 1 year of 47.3% and at 2 years of 27.6%. We compared the demographic data and survival times of these females with those of males with a chronic bleeding disorder and AIDS, and with those of nonhemophilic females with AIDS whose exposure to the human immunodeficiency virus (HIV) was through receipt of blood transfusions, blood components, or tissue. The principal demographic difference was age distribution. The females with chronic bleeding disorders tended to be younger than the transfused, nonhemophilic females, but older than the males. The survival time from AIDS diagnosis to death for the females with chronic bleeding disorders did not differ statistically from that of the other two groups, although older nonhemophilic females whose exposure was transfusion may progress more rapidly to AIDS. PMID- 1503096 TI - Protein C survival during replacement therapy in homozygous protein C deficiency. AB - Homozygous protein C (PC) deficiency is a rare genetic defect that usually results in fatal thrombotic complications (purpura fulminans and DIC), but it can be successfully managed with oral anticoagulants or PC replacement. The successful use of PC replacement for two individuals is described. The activity and antigen levels of PC in fresh frozen plasma (FFP) and prothrombin complex concentrate (PCC) are also reported. The concentration of PC in FFP is 87 +/- 15 units/dl. PC is present in all PCC analyzed; however, a ten-fold difference between the various brands and/or lots is noted. The PC activity and antigen correlates well with no significant levels of APC. Upon infusion of FFP into two homozygous PC-deficient children, the PC levels obtained were less than or equal to 30 units/dl post-infusion and undetectable after 12-18 hr. With infusions of PCC, plasma levels of PC obtained were 100-145 units/dl and less than 10 units/dl after 48 hr. The percent recovery and half-lives of PC from FFP and PCC were 49.8% and 7.8 hr, and 84% and 7.4 hr, respectively. One infant was treated every 48 hr for 2 years without significant purpura fulminans or DIC complications. The levels of the other PC system components did not change during the infusion of the PC-rich material. Based on this information, a specific replacement protocol has been developed using a PC-rich concentrate. However, several problems may arise with the "less pure" PC-rich concentrates: catheter-tip thrombosis, related large vessel thrombosis and blood-transmitted diseases. With a specific PC concentrate, replacement therapy is a viable alternative for the long-term management/treatment of homozygous PC deficiency. PMID- 1503097 TI - Allogeneic bone marrow transplantation for hematological malignancies following etoposide, cyclophosphamide, and fractionated total body irradiation. AB - Forty-three patients received etoposide, cyclophosphamide, and fractionated total body irradiation before allogeneic marrow transplantation. Fifteen patients had chronic myelogenous leukemia in chronic phase or acute leukemia in first remission (standard risk) and twenty-eight patients with more advanced disease (high risk). All patients received etoposide 1,500 mg/m2 intravenously on day -8, cyclophosphamide 60 mg/kg/day intravenously on days -7 and -6, and total body irradiation at 170 cGy twice a day on days -3, -2, and -1. During the first 100 days 12 high risk patients (43%) died from causes unrelated to relapse while none of the standard risk patients died. Renal and hepatic dysfunction were also significantly increased during the first 14 days in the high risk group. The addition of 1,500 mg/m2 of etoposide to the cyclophosphamide and total body irradiation was well tolerated for patients with standard risk. However, the regimen was poorly tolerated with high mortality in patients with more advanced disease. PMID- 1503098 TI - Recombinant interferon-alpha 2A as maintenance treatment for patients with advanced stage chronic lymphocytic leukemia responding to chemotherapy. AB - Forty-five patients suffering from advanced B-CLL were randomized to receive interferon-alpha (IFN alpha) or no treatment after achieving complete remission or partial response, following a chemotherapy protocol called MiNa. The two groups were fully comparable in terms of clinical characteristics and level of response obtained by chemotherapy. IFN alpha was given at a dose of 3 megaunits three times a week intramuscularly for 1 year. The IFN-treated patient group showed a significantly longer duration of response and a less frequent incidence of infections as compared to the no treatment group. A minority of patients who had had partial response to chemotherapy obtained complete remission while on therapy with IFN alpha. Toxicity was mild and patient compliance was excellent. We conclude that IFN alpha may have a role as maintenance therapy in CLL for patients responding to chemotherapy. PMID- 1503099 TI - Cyclosporine and prednisone therapy for pure red cell aplasia in patients with chronic lymphocytic leukemia. AB - We describe the characteristics of response to treatment with cyclosporine (CYA) plus prednisone in seven episodes of pure red cell aplasia (PRCA) in four patients with B cell chronic lymphocytic leukemia (CLL). Fourteen episodes of PRCA occurred in four patients with CLL. Eleven episodes were treated with conventional therapies which included an alkylating agent and prednisone. Four episodes that failed to respond to conventional therapies and an additional three episodes were treated with CYA and prednisone. Six of the seven episodes, including three of four which had failed conventional therapies, responded to CYA plus prednisone compared with six of eleven episodes treated with conventional therapies. Response to CYA and prednisone occurred without a reduction in leukemic mass. In contrast, PRCA remission did not occur until after leukemic mass reduction in three of four patients treated successfully with conventional therapies. Time to response was shorter (14 +/- 3 days) with CYA plus prednisone than with conventional therapies (154 +/- 97 days) in three of four patients. These results indicate that CYA plus prednisone is an effective therapy for the induction of remission from PRCA in patients with CLL. PMID- 1503100 TI - Coexistence of congenital afibrinogenemia and protein C deficiency in a patient. AB - A rare association of congenital afibrinogenemia and hereditary protein C deficiency is described in a 37-year-old female who suffered from ischemic necrosis in the left first toe. The diagnosis of afibrinogenemia was assessed by the absence of fibrinogen in clotting and immunological assays. The diagnosis of hereditary heterozygous type I protein C deficiency was based on the evidence of proportional decreases of activity and antigen of plasma protein C in the propositus, her mother, and two maternal aunts. PMID- 1503101 TI - Reduction in tissue iron stores with a new regimen of continuous ambulatory intravenous deferoxamine. AB - A new regimen of 24-hr ambulatory continuous intravenous infusion of deferoxamine (CIV DFO) through central venous ports was instituted in nine patients aged (mean +/- SD) 22.4 +/- 5.8 years over a period of 15.7 +/- 7.3 months. Central venous infusion sites were changed weekly in the clinic, eliminating the necessity for reconstitution of DFO and needle insertion at home. Because CIV DFO could be interrupted only by medical personnel, patient compliance was documented accurately; patients administered 93.0% +/- 3.2% of CIV DFO prescribed. Mean urinary iron excretion on CIV DFO (66.8 +/- 50.4 mg/24 hr) was significantly greater than that quantitated during 12-hr equivalent-dose subcutaneous DFO infusions (23.4 +/- 18.3 mg/24 hr; P less than 0.025). Mean serum ferritin declined by 71% over the treatment period (P less than 0.005). This regimen confers the advantages of uninterrupted exposure to DFO, is associated with excellent patient compliance, and should be considered in any patient with severe iron overload and erratic compliance with DFO. PMID- 1503102 TI - Mixed type cryoglobulinemia found by an abnormal RBC cytogram in an automated cell counter. PMID- 1503103 TI - Acute onset of juvenile myelodysplastic syndrome mimicking thrombotic thrombocytopenic purpura and rapidly evolving in overt myeloid leukemia. PMID- 1503104 TI - A new case of Passovoy defect. PMID- 1503105 TI - Corticosteroid induced tumor lysis syndrome in acute lymphoblastic leukemia. PMID- 1503106 TI - Desferrioxamine in the treatment of plasmodium falciparum malaria. PMID- 1503107 TI - Immune Bernard Soulier-like syndrome associated with anti-glycoprotein-IX antibody. PMID- 1503108 TI - Successful treatment of thrombotic thrombocytopenic purpura with high-dose corticosteroid. PMID- 1503109 TI - Pruritus secondary to hydroxyurea therapy in a woman with polycythemia vera. PMID- 1503110 TI - Clinical aspects of chronic myeloproliferative diseases. AB - The nonleukemic chronic myeloproliferative disorders, polycythemia vera, essential thrombocytosis, and myeloid metaplasia with myelofibrosis, are clonal disorders with similar but distinct clinical and laboratory findings. This review will discuss the diagnostic criteria for each disease, the variable clinical picture, and the therapeutic modalities, actual and theoretical. PMID- 1503111 TI - Clonality in myeloproliferative disorders. AB - The myeloproliferative disorders are a group of hematologic diseases that are believed to arise from somatic mutations in an early hematopoietic stem cell. This statement is based on the demonstration of monoclonal involvement of terminally differentiated myeloid and lymphoid elements. The techniques for establishing clonal derivation of cells are discussed and the application of these techniques to myeloproliferative diseases is reviewed. The evidence for limited myeloid involvement, lineage heterogeneity, in some patients with myeloproliferative disorders is summarized. PMID- 1503112 TI - Prospects for gene therapy in acute lung injury. AB - Gene transfection is an extremely useful tool with which to explore mechanisms of gene regulation, to examine the molecular physiology of proteins in cultured cells, and to produce transgenic organisms. Several transfection techniques that employ viral and nonviral vectors have been used successfully to transfect functional genes into lung cells in vivo. This report reviews some of the gene transfection techniques that have been applied to the intact lung, an organ that offers unique challenges and opportunities. Results indicate that somatic cell gene therapy is feasible and that gene-based therapies can be developed for acute and chronic lung diseases. PMID- 1503113 TI - Pulmonary endothelial cell pathobiology: implications for acute lung injury. AB - Pulmonary endothelial cells form a continuous monolayer on the luminal surface of the lung vasculature. Until the mid-1970s, the pulmonary endothelium was felt to provide little more than a passive surface for the exchange of gases, water, macromolecules, and some cell traffic. Recent evidence indicates that the pulmonary endothelium is a metabolically active surface, which provides a regulatory interface for the continual processing of blood-borne vasoactive molecules, plays an active role in hemostasis and immunologic and inflammatory events, regulates vascular tone, and interacts with inflammatory cells and neighboring vascular cell types. These metabolic properties are both constitutive and capable of being induced in response to stimuli or injury. Virtually any agent that causes pulmonary endothelial cell injury will lead to impairments in the functional metabolic properties of these cells, resulting in alterations in hemodynamics, hemofluidity, permeability, gas exchange, and intercellular signaling. The net result in the lung is often the clinical picture of acute lung injury with respiratory distress, refractory hypoxemia, diffuse alveolar infiltrates, and respiratory failure. PMID- 1503114 TI - The relationship of total lymphocyte count to CD4 lymphocyte counts in patients infected with human immunodeficiency virus. AB - A simple, inexpensive alternative to CD4 counts would facilitate the management of asymptomatic and early symptomatic patients with HIV infection. In this report, a high correlation was found between CD4 counts and total lymphocyte counts calculated from complete blood counts in a cohort of ambulatory HIV infected patients. Using these data, patients with CD4 counts above and below 500 cells/mm3, 200 cells/mm3, and those with and without symptoms can be identified with a high degree of predictive value. The availability and lower cost of lymphocyte counts make them an attractive alternative to CD4 counts in managing asymptomatic and early symptomatic patients with HIV infection. PMID- 1503115 TI - Impact of hemodialysis on left and right ventricular Doppler diastolic filling indices. AB - Hemodialysis is associated with acute reduction in intravascular volume. To assess the impact of volume reduction on left and right ventricular diastolic filling indexes obtained by Doppler echocardiography, 24 patients on chronic hemodialysis were consecutively studied before, during, and immediately after one hemodialysis session. Twenty four normal sex and age-matched volunteers served as a control group. Study patients had abnormal diastolic indexes when compared to controls. At 2 hours of dialysis (mid dialysis) there was a significant decrease in peak early mitral flow velocity (E), no change in peak atrial filling velocity (A), and a reduction in the E/A ratio. The deceleration time of the mitral E wave also was prolonged compared to baseline. Similar findings were observed with respect to right ventricular filling indices. These changes occurred during the first 2 hours of dialysis and remained unaltered at end dialysis. When patients were subdivided according to weight loss, only the group that lost 1 or more kilograms had significant changes in the Doppler parameters of the left and right ventricle, as well as reduction of the left ventricular dimensions. These findings suggest that preload reduction is the main mechanism that accounts for acute changes in Doppler diastolic indices observed during hemodialysis. PMID- 1503116 TI - Ischemic acute renal failure. AB - Underperfusion of the kidneys often results in the development of ischemic acute renal failure. This review summarizes the recent developments in the understanding of the pathophysiology, diagnosis, and treatment of this serious and costly disorder that affects almost 5% of hospitalized patients. PMID- 1503117 TI - Feeding adaptations in New World primates: an evolutionary perspective: introduction. PMID- 1503118 TI - Systematics and body size: implications for feeding adaptations in New World monkeys. AB - The relationship between body size and feeding ecology is well established for primates. It is argued that the evolutionary history of modern New World monkeys and, in particular, the path to attainment of current body size is significant in understanding the similarities and differences between dietary strategies and other ecological parameters of similar-sized monkeys. Current interpretations of New World monkey evolutionary relationships are reviewed. Based on a synthesis of available body weights and the assumption that the earliest New World monkeys weighed close to 1 kg, similar to modern Aotus and Callicebus, predicted patterns of body size change in each lineage are given. Restrictions on directions of body size change in primates are discussed, and it is shown that "Stanley's Rule" offers a good explanation for differing body size ranges in New and Old World anthropoids. Predicted ecological correlates to body size drawn from the mammalian literature are offered and tested using data on New World monkeys, which show some concurrence and several interesting departures from predicted patterns. Sexual dimorphism in body weight of New World monkey species is reviewed, based on the new summary of body weight data given. PMID- 1503119 TI - Vertical clinging, small body size, and the evolution of feeding adaptations in the Callitrichinae. AB - Primates of the subfamily Callitrichinae (Callimico, Callithrix, Leontopithecus, and Saguinus) are small-bodied New World monkeys (105-700 g) possessing clawlike nails on all manual and pedal digits excluding the hallux. Specialized nails in these genera serve a critical function in feeding by enabling tamarins and marmosets to cling to trunks and other large vertical supports while exploiting food resources. Within the subfamily, there is evidence of at least four distinct large-branch feeding patterns. These include (1) seasonal exudate feeding and occasional trunk foraging (many Saguinus spp.); (2) exploitation of bark surface insects and the use of trunks as a platform to locate terrestrial prey (Saguinus fuscicollis, S. nigricollis, and Callimico); (3) manipulative foraging and bark stripping to locate concealed insects and small vertebrates (Leontopithecus); and (4) tree gouging and year-round exudate feeding (many Callithrix). Large-branch feeding and the use of vertical clinging postures appear to be a primary adaptation among virtually all callitrichines, distinguishing them ecologically from other platyrrhine taxa. Given the anatomy and behavior of extant callitrichines, Saguinus appears to be the most ecologically generalized member of this subfamily, and species of this genus may provide useful models for reconstructing the feeding and foraging adaptations of early callitrichines. PMID- 1503120 TI - Morphological and behavioral adaptations for foraging in generalist primates: the case of the cebines. AB - In addition to being frugivorous, Cebus and Saimiri stand out among the New World primates of similar body size in being heavily dependent on animal matter for protein (faunivory). A detailed description of the morphology and behavior of the two genera is presented with the object of evaluating the interaction and respective contributions of morphological and behavioral adaptations to foraging patterns. Our conclusions include the following: First, body size is extremely important in explaining the observed variation in diet. Second, the emphasis on faunivory is facilitated more by behavioral than by morphological specialization. Third, whatever morphological specializations are present, particularly in Cebus, are probably favored by diet at the most food-depauperate time of year. Fourth, although morphology may well reveal what a primate may potentially eat, to map this potential onto actual diet requires a detailed knowledge of its natural ecosystem. Finally, we consider whether the behavioral data support the tenuous morphological evidence for grouping Cebus and Saimiri within the clade Cebinae. PMID- 1503121 TI - Dietary and dental adaptations in the Pitheciinae. AB - Since Mivart (1865), Cacajao, Chiropotes, and Pithecia have been grouped into a single taxon, which he called the subfamily Pitheciinae but which I, following Rosenberger (this issue), refer to as the living members of the tribe Pitheciini. While few today doubt the association of these three living genera, not all would place them together with Aotus and Callicebus in the subfamily Pitheciinae. This is an attempt to sort out the behavioral and morphological features of feeding and dental morphology in these taxa. Extant members of the tribe Pitheciini are adapted for sclerocarpic foraging, morphological evidence for which is found in the fossils of Soriacebus and Cebupithecia. Sclerocarpic foraging in living pitheciins is a two-stage process of seed predation involving 1) specialized features of the anterior dentition that allow removal of a hard pericarp that protects a seed or seeds, followed by 2) mastication by the posterior dentition having low cusp relief to triturate nutritious seeds of a relatively soft and uniformly pliable consistency. The dentitions of fossil pitheciins, Soriacebus and Cebupithecia, demonstrate that the hypertrophy of lower incisors plus the robustness and flaring of the canine precede development of low cusp relief on molars and premolars in the evolution of morphological features associated with sclerocarpic foraging. Features of sclerocarpic foraging are found less uniformly in the other two pitheciines, Callicebus and Aotus. PMID- 1503122 TI - Atelinae adaptations: behavioral strategies and ecological constraints. AB - Comparisons between the four genera that make up the Atelinae reveal two distinct behavioral patterns, one in which energy expenditure is minimized (Alouatta) and one in which energy intake is maximized (Lagothrix, Ateles, and Brachyteles). Among the atelins, Lagothrix and Ateles devote over 75% of their annual feeding time to fruit, while Brachyteles devotes between 50% and 67% of their feeding time to leaves. Pronounced seasonality in the Atlantic coastal forest inhabited by Brachyteles may be responsible for its more folivorous diet. Alouatta falls in the body size range of Lagothrix and is much smaller than Ateles and Brachyteles. Nonetheless, Alouatta is more folivorous than sympatric atelins. The atelins also share a rapid, suspensory mode of locomotion that appears to enable them to minimize travel time between widely dispersed fruit sources. Alouatta, by contrast, employs a slower, but more energetically efficient, quadrupedal locomotion. Ranging patterns among the Atelinae are consistent with both diet and locomotor abilities: Atelins travel daily distances up to 5,000 m; Alouatta ranges are much shorter. Further distinctions are evident in Atelinae grouping patterns. Alouatta remains in small cohesive groups that occupy home ranges less than 60 ha in size. Both Lagothrix and Ateles have large groups that fission to reduce the costs of intragroup feeding competition when preferred fruits occur in small patches within much larger community ranges. While greater reliance on low energy foods such as leaves may release Brachyteles from similar competitive constraints, their tendency toward fluid grouping associations is consistent with the pursuit of a frugivorous diet. PMID- 1503123 TI - Evolution of feeding niches in New World monkeys. AB - The adaptive radiation of modern New World monkeys unfolded as the major lineages diversified within different dietary-adaptive zones predicated upon a fundamentally frugivorous habit. The broad outlines of this pattern can be seen in the fossil record, beginning in the early Miocene. Cebids are obligate frugivorous predators. The smallest forms (Cebuella, Callithrix) are specialized exudativores, and the largest (cebines) are seasonally flexible omnivores, feeding particularly on insects (Saimiri) or "hard" foods, such as pith and palm nuts (Cebus), when resources are scarce. The smaller-bodied atelids (Callicebus, Aotus) may use insects or leaves opportunistically, but pitheciins (saki-uakaris) specialize on seeds as their major protein source. The larger atelines (Alouatta, Brachyteles) depend on leaves or on ripe fruit (Ateles). Locomotion, body size, and dietary adaptations are linked: claws and small body size opened the canopy subcanopy niche to callitrichines; climbing and hanging, the fine-branch setting to the atelines; large size and strength, semiprehensile tails, and grasping thumbs, the extractive insectivory of Cebus; deliberate quadrupedalism, the energy-saving transport of folivorous Alouatta. Body size increases and decreases occurred often and in parallel within guilds and lineages. Conventional dietary categories, particularly frugivory, are inadequate for organizing the behavioral and anatomical evidence pertinent to evolutionary adaptation. Related models of morphological evolution based on feeding frequencies tend to obfuscate the selective importance of "critical functions," responses to the biomechanically challenging components of diet that may be determined by a numerically small, or seasonal, dietary fraction. For fossils, body size is an unreliable indicator of diet in the absence of detailed morphological information. More attention needs to be given to developing techniques for identifying and quantifying mechanically significant aspects of dental form, the physical properties of primate foods, their mode of access, and the cycles of availability and nutritional value. PMID- 1503124 TI - Reflections on humane values and biopsychosocial integration. PMID- 1503125 TI - Patient care for the twenty-first century. PMID- 1503126 TI - Lawrence Hartmann, M.D., one hundred twentieth president, 1991-1992. PMID- 1503127 TI - Judicial and legislative responses to cost containment. AB - Cost containment through reduction of insurance benefits and aggressive utilization review is increasingly risking the sacrifice of good clinical care in the pursuit of financial objectives. This article provides examples of judicial and legislative responses to perceived fiscal intrusions into clinical practice. Principles for asserting clinical goals in the cost containment process are also provided to assist in the inevitable negotiations and battles ahead. PMID- 1503128 TI - Association of beta-endorphin with specific clinical symptoms of depression. AB - OBJECTIVE: Abnormalities in plasma concentrations of beta-endorphin-like immunoreactivity (beta-endorphin) have been reported in depressed patients. This study was done to test the hypothesis that specific clinical characteristics of depression are associated with plasma beta-endorphin concentration. METHOD: Plasma beta-endorphin was evaluated in 20 depressed patients diagnosed according to DSM-III-R and in 23 age- and sex-matched comparison subjects, and each was evaluated with the structured Schedule for Affective Disorders and Schizophrenia (SADS). Twelve SADS items involving dysphoric mood and related symptoms were chosen for analysis. RESULTS: Within the group of all 43 subjects and within the depressed group, beta-endorphin level correlated significantly with psychic anxiety and with phobia. In the depressed group only, beta-endorphin also correlated significantly with obsessions/compulsions. Concentration of beta endorphin was not significantly correlated with score on the Hamilton Rating Scale for Depression or Beck Depression Inventory or with scores on other SADS symptom items, including somatic anxiety, insomnia, subjective anger, overt anger, agitation, psychomotor retardation, panic attacks, appetite loss, or total weight loss. In the group of 23 comparison subjects, beta-endorphin did not correlate with Beck or Hamilton depression score or with any of the SADS clinical variables. CONCLUSIONS: High levels of plasma beta-endorphin may be associated with more severe anxiety, phobia, and obsessions/compulsions in depressed patients. PMID- 1503129 TI - Prevalence of seasonal affective disorder in Alaska. AB - OBJECTIVE: The goals of this study are to provide estimates of the prevalence of seasonal affective disorder in Alaska, to examine sociodemographic correlates, and to evaluate the relation between seasonal affective disorder and general depression. METHOD: A random sample of 283 residents of Fairbanks who had lived in Alaska for 3 years or more were interviewed with the Seasonal Pattern Assessment Questionnaire and the Center for Epidemiologic Studies Depression Scale (CES-D Scale). RESULTS: Twenty-six (9.2%) of the subjects met diagnostic criteria for seasonal affective disorder, one of the highest figures yet reported. These cyclic winter affective disorders occurred more often in women than men (ratio = 3:2) and were less prevalent among residents who were older than 40 years of age. Assessment of depression with the CES-D Scale supported the diagnostic classification of respondents and the differentiation of seasonal affective disorder from other depression. CONCLUSIONS: This study supports the conclusions that seasonal affective disorder is prevalent in northern populations and that sex and age may represent the major risk factors that differentiate it from the general experience of depression in northern communities. PMID- 1503130 TI - Duration of psychosis and outcome in first-episode schizophrenia. AB - OBJECTIVE: This study was undertaken to assess the potential effect of duration of untreated illness on outcome in a group of first-episode schizophrenic patients. METHOD: Seventy patients with schizophrenia diagnosed according to the Research Diagnostic Criteria entered the study and were followed for up to 3 years. All patients received standardized treatment and uniform assessments both during the acute phase of their illness and throughout the follow-up period. Outcome was measured in terms of time to remission of acute psychotic symptoms as well as degree of symptom remission. RESULTS: The mean duration of psychotic symptoms before initial treatment was 52 weeks, preceded by a substantial prepsychotic period. According to survival analysis, duration of illness before treatment was found to be significantly associated with time to remission as well as with level of remission. The effect of duration of illness on outcome remained significant when diagnosis and gender variables, themselves associated with outcome, were controlled in a regression analysis. Duration of illness was not correlated with age at onset, mode of onset, premorbid adjustment, or severity of illness at entry into the study. CONCLUSIONS: Duration of psychosis before treatment may be an important predictor of outcome in first-episode schizophrenia. Acute psychotic symptoms could reflect an active morbid process which, if not ameliorated by neuroleptic drug treatment, may result in lasting morbidity. Further implications of these findings are discussed. PMID- 1503131 TI - Cigarette smoking in schizophrenia: relationship to psychopathology and medication side effects. AB - OBJECTIVE: The authors' goal was to study the relationship between smoking status and clinical characteristics in schizophrenic patients. METHOD: Seventy-eight schizophrenic outpatients were assessed by a single rater using the Brief Psychiatric Rating Scale (BPRS), the Abnormal Involuntary Movement Scale, and the Simpson-Angus Scale for extrapyramidal symptoms. Current smokers (N = 58) were compared with nonsmokers (N = 20) on clinical variables by independent t tests and chi-square tests. Differences in outcome variables were tested by multiple analysis of covariance (ANCOVA) with smoking status and gender as factors and age, neuroleptic dose, and caffeine consumption as covariates. RESULTS: Seventy four percent of patients were current smokers and reported a mean of 19 cigarettes smoked per day. Compared to nonsmokers, current smokers were significantly more likely to be men, to be younger, and to have had an earlier age at onset and a greater number of previous hospitalizations. Current smokers and nonsmokers received mean neuroleptic doses of 1160 and 542 mg/day (chlorpromazine equivalents); the difference was significant. Current smokers also displayed significantly less parkinsonism and more akathisia and had higher total scores on the BPRS. Overall multiple ANCOVA demonstrated a significant main effect for smoking status but not gender or the interaction between gender and smoking status. Univariate ANCOVAs demonstrated a significant main effect of smoking status only for the Simpson-Angus Scale score. CONCLUSIONS: Cigarette smokers receive significantly higher neuroleptic doses, in part because of a smoking-induced increase in neuroleptic metabolism. Smoking is also associated with significant reduction in levels of parkinsonism. Smoking status is a significant factor that should be considered in assessment of neuroleptic dose requirements and neuroleptic side effects. PMID- 1503132 TI - Sylvian fissure size in schizophrenia measured with the magnetic resonance imaging rating protocol of the Consortium to Establish a Registry for Alzheimer's Disease. AB - OBJECTIVE: Since previous work indicated smaller than normal temporal lobe structures in schizophrenic patients, the authors tested the hypothesis that this abnormality might be reflected in abnormally large sylvian fissures. METHOD: The subjects were 48 schizophrenic patients and 51 normal comparison subjects matched groupwise with regard to age and sex. CSF spaces (sylvian fissures, temporal lobe sulci, temporal horns, third ventricle, lateral ventricles, and superficial cerebral sulci) were visually assessed with the magnetic resonance imaging rating protocol of the Consortium to Establish a Registry for Alzheimer's Disease (CERAD). RESULTS: The sylvian fissures of the schizophrenic patients were found to be bilaterally wider than those of the comparison subjects. There were no other significant differences. CONCLUSIONS: Schizophrenic patients appear to have larger than normal sylvian fissures, which may reflect smaller superior temporal gyri. PMID- 1503133 TI - Predicting feasibility of day treatment for unselected patients referred for inpatient psychiatric treatment: results of a randomized trial. AB - OBJECTIVE: Because previous studies of day treatment as an alternative to inpatient treatment had major disadvantages or methodological shortcomings, the authors conducted a randomized controlled trial to estimate and predict the extent to which day treatment is feasible for unselected patients referred for inpatient treatment. METHOD: Of 160 patients, 57 were randomly assigned to the control condition and 103 were assigned to the experimental condition. Control patients received standard clinical care. In the experimental condition, day treatment was attempted as soon as the patient's condition permitted. The average number of nights per week that experimental patients spent away from the hospital was compared to the average number of nights away for patients under standard care. RESULTS: Day treatment was satisfactory for 40% of the experimental patients but was completely infeasible for another 40%. The level of surveillance needed in the first week, physical illness, number of previous admissions, depressive symptoms, and treatment by qualified psychiatrists versus registrars were variables predictive of these differences. CONCLUSIONS: In this unselected group of patients, no absolute contraindications against day treatment were found. This suggests that the selection criteria applied in nearly all other controlled studies on the subject were unwarranted. The approach used in this study facilitated treatment in the least restrictive environment possible. PMID- 1503134 TI - An evaluation of the Cleveland criteria for inpatient treatment of substance abuse. AB - OBJECTIVE: This study examined the validity of the Cleveland Admission, Discharge, and Transfer Criteria, a comprehensive system for assigning alcohol- and drug-abusing patients to appropriate levels of care. METHOD: The subjects were 143 alcoholic and cocaine-dependent male patients in an intensive Veterans Administration day treatment program for substance abusers. Patients who should have received inpatient treatment according to the Cleveland criteria were compared with those who were properly "matched" to day treatment according to the criteria. The outcome measures were treatment completion, results of urine toxicology screens, and self-reports of substance use and psychosocial functioning. RESULTS: Patients who met the criteria for inpatient care were not more likely to drop out of day hospital treatment, and there was no evidence that they were drinking or using cocaine more frequently during follow-up. Furthermore, they did not appear to be doing worse on any of the other outcome measures, with the exception of psychological status. CONCLUSIONS: The results suggest that for male substance abusers in the lower socioeconomic levels, the Cleveland criteria may not be effective in differentiating patients who can manage well with day hospital treatment and those who require inpatient treatment. PMID- 1503135 TI - Mental health status and community adjustment after treatment in a residential treatment program for homeless veterans. AB - OBJECTIVE: An uncontrolled outcome study was conducted to examine clinical improvement and the relationship of psychiatric and substance abuse problems, community adjustment, and housing status among homeless veterans who participated in a multisite residential treatment program. METHOD: The study was performed at three U.S. Department of Veterans Affairs medical centers in Florida, Ohio, and California. Baseline, discharge, and 3-month postdischarge follow-up data were collected for 255 veterans admitted to the Domiciliary Care for Homeless Veterans Program. Multiple dimensions of outcome were examined, including psychiatric symptoms, alcohol abuse, drug abuse, social contacts, income, employment, and housing. RESULTS: Program participation was found to be associated with improvement in all areas of mental health and community adjustment. Improvement in psychiatric symptoms was associated with superior housing outcomes and improvement in community adjustment. When correlates of improvement in alcohol and drug abuse were examined, only one of eight possible relationships was found to be significant: improvement in alcohol problems was positively associated with improvement in employment. CONCLUSIONS: Homeless mentally ill veterans derive clear benefits from participation in a multidimensional residential treatment program. Improvement in mental health problems, however, is weakly linked to improvement in other areas, suggesting that treatment programs may have to attend separately to multiple domains of life adjustment. PMID- 1503136 TI - Sensitivity of psychiatric diagnosis based on the best estimate procedure. AB - OBJECTIVE: A "best estimate" diagnosis is one made by expert clinicians on the basis of diagnostic information from direct interview conducted by another clinician plus information from medical records and from reports of family members. The authors address the question of whether the best estimate procedure can enhance the classification of psychiatric diagnoses of subjects who are interviewed directly. METHOD: Four hundred seventy-five subjects were interviewed directly: 201 opiate-addicted probands who sought treatment from a university based clinic and 274 of their spouses and/or first-degree relatives. Subjects were interviewed by trained clinical assessors using the Schedule for Affective Disorders and Schizophrenia and classified according to Research Diagnostic Criteria. Two psychologists independently diagnosed the same subjects by applying the best estimate procedure. Lifetime rates of major and minor depressive disorder, antisocial personality, alcoholism, and drug abuse were calculated. The rates of diagnoses made on the basis of direct interviews alone were compared with the rates of diagnoses made according to the best estimate procedure. RESULTS: Higher rates of diagnoses of all four disorders were made when the best estimate procedure was applied than when direct interview alone was used; the best estimate procedure also resulted in a minimal rate of false positives. CONCLUSIONS: The higher rate of diagnoses based on the best estimate procedure may represent an enhancement in the accuracy of psychiatric diagnoses or an increase in erroneous diagnoses. The authors consider the second possibility less likely. PMID- 1503137 TI - The relationship between personality and DSM-III axis I disorders in the population: results from an epidemiological survey. AB - OBJECTIVE: The aim of this study was to assess the relationships between specific personality disorders and DSM-III axis I conditions in a community sample. METHOD: A total of 810 subjects were examined by psychiatrists in the second stage of the Eastern Baltimore Mental Health Survey, part of the Epidemiological Catchment Area Program of the National Institute of Mental Health. A semistructured examination, the Standardized Psychiatric Examination, was employed to assess axis I and axis II conditions. Scales for compulsive and antisocial personality disorders were derived from DSM-III criteria. The relationships between scores on these personality disorder scales and the presence of generalized anxiety disorder, alcohol use disorders (alcohol abuse and alcohol dependence), and simple phobia were evaluated by using logistic regression. RESULTS: Higher compulsive personality scores were associated with a greater odds of generalized anxiety disorder and simple phobia but a smaller odds of alcohol use disorders. In contrast, higher antisocial personality scores were associated with a greater odds of alcohol use disorders but a smaller odds of generalized anxiety disorder. There was no relationship between antisocial personality scores and simple phobia. CONCLUSIONS: Personality disorders have specific relationships to axis I conditions, which suggests different vulnerabilities but also different protective influences. PMID- 1503138 TI - Posttraumatic adaptation and distress among adult burn survivors. AB - OBJECTIVE: The purpose of this study was to examine the prevalence, natural history, and psychosocial impact of posttraumatic symptoms in adult burn survivors. METHOD: Forty-three adult inpatients at a regional burn center were assessed at discharge with standardized instruments to determine the presence of psychiatric disorder, assess personality, and quantify depression. Thirty-one patients were evaluated 4 months after discharge. RESULTS: Posttraumatic stress disorder was diagnosed in 7% of patients at discharge and in over 22% of patients at follow-up. Symptoms of avoidance and emotional numbing (DSM-III-R criterion C symptoms) tended to emerge after discharge from the hospital. While posttraumatic symptoms were associated with symptoms of depression, they were not strongly associated with psychosocial adjustment to illness; psychosocial adjustment was more strongly related to aspects of personality, the injury itself, and its treatment. CONCLUSIONS: Since adult burn survivors often develop new symptoms of posttraumatic distress after leaving the hospital, longitudinal surveillance is required to detect new cases and provide appropriate treatment. Survivors at risk for poor psychosocial adjustment after discharge may be identifiable during hospitalization, and preventive treatment strategies should be developed and tested for this population. PMID- 1503139 TI - Pubertal stage and panic attack history in sixth- and seventh-grade girls. AB - OBJECTIVE: Although the incidence of first panic attacks appears to peak during adolescence, little is known about which features of adolescence contribute to the risk of a first panic episode. The purpose of this study was to compare the relative importance of age and pubertal stage in explaining the occurrence of panic attacks in adolescents. METHOD: From a school-based sample of sixth- and seventh-grade girls, 754 subjects completed both a structured clinical interview determining history of one or more panic episodes and a self-assessment of Tanner stages of pubertal development. A multiple logistic regression analysis was performed with panic attack history as the dependent variable and pubertal stage, age, and their interaction as the independent variables. RESULTS: A history of one or more four-symptom panic attacks was found in 5.3% of the girls (N = 40). After age was controlled for, pubertal stage was significantly related to panic attack history. At each age, higher rates of panic attacks were found in the more physically mature girls. CONCLUSIONS: Pubertal stage, after adjustment for the effects of age, appears to predict panic attack occurrence in young adolescent girls. Understanding the link between puberty and panic may offer clues regarding the onset and etiology of panic attacks. PMID- 1503140 TI - Tics and Tourette's disorder: a 2- to 7-year follow-up of 54 obsessive-compulsive children. AB - OBJECTIVE: This study examined a hypothesized etiologic relationship between Tourette's disorder and obsessive-compulsive disorder. METHOD: Fifty-four children who had initially participated in treatment protocols for obsessive compulsive disorder (Tourette's disorder was an exclusionary criterion) were reevaluated 2-7 years later with a neurological examination and a structured interview to establish the presence or absence of tics and Tourette's disorder. The children's first-degree relatives (N = 171) were also screened for tic disorders. RESULTS: At baseline, 57% (N = 31) of the patients had lifetime histories of tics. At follow-up, 59% (N = 32) had lifetime histories of tics; eight of these (all males) met the criteria for Tourette's disorder (six had developed the disorder, and two, it could be argued in retrospect, might have met the criteria at baseline). The patients with lifetime histories of tics had greater anxiety, a higher ratio of CSF 5-hydroxyindoleacetic acid to homovanillic acid, and a younger age at onset of obsessive-compulsive disorder than those without tics. The patients with Tourette's disorder differed from other male patients only in having an earlier age at onset of obsessive-compulsive disorder. Of the first-degree relatives, 1.8% (N = 3) had Tourette's disorder, and 14% (N = 24) had a tic disorder. CONCLUSIONS: Except for their earlier age at onset of obsessive-compulsive disorder, the patients with Tourette's disorder were indistinguishable from those without. The apparent high rate of tics and Tourette's disorder in the subjects and their relatives is consistent with the hypothesis that in some cases, obsessive-compulsive disorder and Tourette's disorder may be alternative manifestations of the same underlying illness. PMID- 1503141 TI - Differences in neuropsychological and academic achievement between adolescent delinquents and status offenders. AB - OBJECTIVE: This study sought to determine whether neurocognitive factors could discriminate delinquents brought before a juvenile court in a large urban area from nondelinquent status offenders brought before the same court. METHOD: Psychological tests were administered to 216 adolescents, aged 13-15 years, presenting to a large urban juvenile court. One hundred ten delinquents (65 male and 45 female) were compared to 106 high-risk nondelinquents (65 male and 41 female) on the WISC-R subtests, the Wide Range Achievement Test, and the Memory for Designs Test. RESULTS: Discriminant analysis revealed that the male delinquents could not be discriminated from the comparison group of male status offenders on the basis of scores on any of the measures. Among the female subjects, scores on reading, arithmetic, digit span, and picture completion subtests and the Memory for Designs Test differed significantly between groups, with some of the findings favoring status offenders and others favoring delinquents. CONCLUSIONS: Overall, the findings did not support the hypothesis that inferior intelligence is an independent risk factor for delinquent behavior. PMID- 1503142 TI - Intravenous versus intramuscular atropine in ECT. AB - Twelve patients receiving ECT consented to random assignment to either intravenous or intramuscular administration of atropine for a total of 48 ECTs. There were no statistically significant differences between routes of administration in heart rate, blood pressures, or sialorrhea, but intravenous administration eliminated one injection per treatment and the development of dry mouth and tachycardia between the intramuscular injection and ECT. The authors recommend that atropine for ECT be administered intravenously. PMID- 1503143 TI - Addition of fluoxetine to clozapine. PMID- 1503144 TI - Polyserositis associated with clozapine treatment. PMID- 1503146 TI - Major depression or alcohol-induced organic affective syndrome? PMID- 1503145 TI - Disulfiram toxicity and catatonia in a forensic outpatient. PMID- 1503148 TI - New name for ECT could backfire. PMID- 1503147 TI - Protecting patients from clinician-patient sexual contact. PMID- 1503149 TI - Borderline personality disorder in incest victims. PMID- 1503150 TI - The treatment of catatonia: benzodiazepines of ECT? PMID- 1503151 TI - Childhood factors in adult self-destructive behavior. PMID- 1503152 TI - Antidepressants and the treatment of stuttering. PMID- 1503153 TI - Alexithymia and the ECA study. PMID- 1503154 TI - Antidepressant-induced mania in obsessive-compulsive disorder. PMID- 1503155 TI - Simple schizophrenia, negative symptoms, and prefrontal hypodopaminergia. PMID- 1503157 TI - Featuring smoking and health. PMID- 1503156 TI - The vital diversity of tobacco control research. PMID- 1503158 TI - Creating a healthy public. AB - Significant change in thought and action will be required for our health system to become capable of serving all citizens effectively. Reliance on market forces and political expediency to shape health policy has focused attention inappropriately on finding ways to pay for illness care rather than maximizing health status. This misdirection of thought and effort has led many of us to search for ways to assure that health policy decisions are consistently based on both science and an ethic of humane concern. Courageous and disciplined local leadership will be needed to motivate policymakers to focus on the task of creating a healthy public. Linkage of academicians and practitioners with the public in a manner than empowers communities to assess and prioritize their own health problems could foster a strong community-based demand for ethical and humane decision making. Constituent demand for improved health status could provide the support politicians need if they are to legislate a national health program that emphasizes health promotion and disease prevention as well as illness care. PMID- 1503159 TI - Communitywide smoking prevention: long-term outcomes of the Minnesota Heart Health Program and the Class of 1989 Study. AB - OBJECTIVES: The Class of 1989 Study is part of the Minnesota Heart Health Program (MHHP), a populationwide research and demonstration project designed to reduce cardiovascular disease in three educated communities from 1980 to 1993. This paper describes an intensive, school-based behavioral intervention on cigarette smoking, comparing long-term outcomes in one of the intervention communities with those in a matched reference community. METHODS: Beginning in sixth grade (1983), seven annual waves of cohort and cross-sectional behavioral measurements were taken from one MHHP intervention community and its matched pair. All students in each community were eligible to participate (baseline n = 2401). Self-reported data collected at each period described prevalence and intensity of cigarette smoking. RESULTS: There were no differences at baseline for either weekly smoking prevalence or intensity of smoking. Throughout the follow-up period, however, smoking rates as determined by these measures were significantly lower in the intervention community: 14.6% of students were weekly smokers at the end of high school compared with 24.1% in the reference community. CONCLUSIONS: These results suggest that multiple intervention components such as behavioral education in schools, booster programs to sustain training, and complementary communitywide strategies may all be needed for lasting reductions in adolescent tobacco use. PMID- 1503160 TI - Locking devices on cigarette vending machines: evaluation of a city ordinance. AB - OBJECTIVES: Policymakers, researchers, and citizens are beginning to recognize the need to limit minors' access to tobacco by restricting the sale of cigarettes through vending machines. One policy alternative that has been proposed by the tobacco industry is a requirement that vending machines be fitted with electronic locking devices. This study evaluates such a policy as enacted in St. Paul, Minn. METHODS: A random sample of vending machine locations was selected for cigarette purchase attempts conducted before implementation and at 3 and 12 months postimplementation. RESULTS: The rate of noncompliance by merchants was 34% after 3 months and 30% after 1 year. The effect of the law was to reduce the ability of a minor to purchase cigarettes from locations originally selling cigarettes through vending machines from 86% at baseline to 36% at 3 months. The purchase rate at these locations rose to 48% at 1 year. CONCLUSIONS: Our results suggest that cigarette vending machine locking devices may not be as effective as vending machine bans and require additional enforcement to ensure compliance with the law. PMID- 1503161 TI - Adolescents' multisubstance use patterns: the role of heavy alcohol and cigarette use. AB - OBJECTIVES: Knowledge about the roles that heavy alcohol and cigarette use play in patterns of concurrent substance use among adolescents is lacking despite studies showing that adolescent substance users are typically multisubstance users and that alcohol and cigarettes are commonly used heavily by those who use illicit substances. METHODS: The roles of increasing use and heavy first-time use of alcohol and cigarettes in multisubstance use patterns were examined in a cohort of 4192 secondary students who were surveyed three times over a 4-year period. RESULTS: When subsequent use patterns were compared for students who increased their levels of alcohol or cigarette use and those who initiated use for the first time but at heavy frequencies, analyses indicated that the former group was more likely to initiate the subsequent use of other substances and to maintain and increase use already initiated. CONCLUSIONS: These results suggest that adolescents are likely to have been involved in a history of licit substance use characterized by increasing levels of use before progressing to and maintaining the use of other substances. Increasing frequencies of alcohol and cigarette use, therefore, may be markers for more serious patterns of substance use. PMID- 1503162 TI - Determinants of passive smoking in children in Edinburgh, Scotland. AB - OBJECTIVES: Using saliva cotinine as a quantitative marker, we examined the contribution of factors other than parental smoking to children's passive exposure to tobacco smoke. METHODS: Saliva specimens from a random sample of 734 7-year-old schoolchildren in Edinburgh, Scotland, were analyzed for cotinine. Their parents completed a questionnaire covering smoking habits and conditions in the home. RESULTS: A number of independent predictors of cotinine were identified in addition to the main one of smoking by household members. These predictors included home ownership, social class, day of the week, season of the year, number of parents present, crowding in the home, the number of children in the household, and sex. Cotinine was higher in children from less advantaged backgrounds, during winter, on Mondays, in girls, and when fewer other children were present. The effects were similar between children from nonsmoking and smoking homes. CONCLUSIONS: Questionnaire measures of parental smoking are insufficient to fully characterize young children's exposure to passive smoking. Because socioeconomic variables contribute to measured exposure, passive-smoking studies that treat class as a confounder and control for it may be overcontrolling. PMID- 1503163 TI - Cigarette smoking and occupational status: 1977 to 1990. AB - OBJECTIVES: In this study we examined the relationship between occupational status and smoking habits in men and women during the period from 1977 to 1990. METHODS: Cigarette smoking and occupational history were obtained from 8045 men and women who served as controls for a hospital-based study of tobacco-related diseases. RESULTS: There was an association between increasing occupational status and tobacco exposure in men, but not in women. The quit rate increased over time in all sex-occupational groups except for male laborers, whose quit rate remained constant. Nicotine-dependent smokers are likely to find it difficult to quit. Male nicotine-dependent smokers were consistently found in greater numbers among blue collar workers throughout the study period. Initially, female nicotine-dependent smokers were more often found among blue collar workers, but in recent years became more frequent among white collar workers. CONCLUSION: These trends provide clues to the future epidemiological distribution of lung cancer and other tobacco-related diseases. An understanding of gender differences in the occupational profile of cigarette smokers can provide guidelines for effective antismoking interventions. PMID- 1503164 TI - Predictors of smoking relapse after noncardiac surgery. Study of Perioperative Ischemia (SPI) Research Group. AB - OBJECTIVES: We studied 235 smokers who were admitted for major noncardiac surgery and who survived hospitalization to determine the frequency and predictors of smoking relapse 1 year after hospitalization. METHODS: We analyzed data collected prospectively from the Study of Perioperative Ischemia. We determined smoking status by self-report. RESULTS: At 12 months posthospitalization, 142 (76%) of the 186 surviving patients had resumed smoking. Significant independent predictors of relapse at 12 months were a history of alcohol abuse and a history of heavy cigarette smoking (P less than 0.01 and P less than 0.05, respectively). CONCLUSIONS: Since smokers commonly undergo surgery, the perioperative period provides a valuable window of opportunity for smoking cessation interventions designed to decrease the high rate of smoking relapse after surgery. PMID- 1503165 TI - Smoking cessation in women concerned about weight. AB - BACKGROUND: Weight gain after smoking cessation is often cited by women smokers as a primary reason for not attempting to quit smoking or for relapsing after a cessation attempt. METHODS: A randomized trial of 417 women smokers was conducted to test the addition of two weight control strategies to a smoking cessation program. Participants received the standard smoking cessation program, the program plus nicotine gum, the program plus behavioral weight control, or the program plus both nicotine gum and behavioral weight control. Weight and smoking status were measured at the end of treatment and at 6 and 12 months posttreatment. RESULTS: Smoking cessation rates were highest in the group receiving the smoking cessation program plus nicotine gum. Weight gain did not vary by treatment condition, so its effect on relapse could not be examined by group. There was no significant relationship between weight gained and relapse in individuals. CONCLUSIONS: The added behavioral weight control program was attractive to the participants and did not reduce smoking cessation rates. However, it did not produce the expected effect on weight, thereby restricting our ability to examine the effect of weight control on smoking cessation and relapse. PMID- 1503166 TI - How women's adopted low-fat diets affect their husbands. AB - OBJECTIVES: One way of promoting a reduction in dietary fat intake is by changing the diet of family members. This study investigated the long-term effects of a low-fat dietary intervention on husbands of women who participated in the Women's Health Trial (WHT). METHODS: An average of 12 months after the end of the WHT, a randomly selected sample of participants' husbands was sent dietary and health questionnaires as part of a follow-up study of the maintenance of the low-fat diet among WHT participants. RESULTS: We found an absolute difference in fat intake between groups of 4 percentage points (32.9% energy from fat among intervention husbands [n = 188] vs 36.9% among control husbands [n = 180]). The wife's attitude and fat intake were among the most important predictors of her husband's fat intake, indicating that the effect of the WHT intervention on the husbands of participants was more likely due to their acceptance of lower-fat foods being served at home than to overt actions by the men. CONCLUSIONS: Our results suggest that a dietary intervention aimed at women can have an effect on their husbands and may be a cost-effective approach to healthy dietary change for both women and men. PMID- 1503167 TI - Weight loss attempts in adults: goals, duration, and rate of weight loss. AB - OBJECTIVES: Although attempted weight loss is common, little is known about the goals and durations of weight loss attempts and the rates of achieved weight loss in the general population. METHODS: Data were collected by telephone in 1989 from adults aged 18 years and older in 39 states and the District of Columbia. Analyses were carried out separately for the 6758 men and 14,915 women who reported currently trying to lose weight. RESULTS: Approximately 25% of the men respondents and 40% of the women respondents reported that they were currently trying to lose weight. Among men, a higher percentage of Hispanics (31%) than of Whites (25%) or Blacks (23%) reported trying to lose weight. Among women, however, there were no ethnic differences in prevalence. The average man wanted to lose 30 pounds and to weigh 178 pounds; the average woman wanted to lose 31 pounds and to weigh 133 pounds. Black women wanted to lose an average of 8 pounds more than did White women, but Black women's goal weight was 10 pounds heavier. The average rate of achieved weight loss was 1.4 pounds per week for men and 1.1 pounds per week for women; these averages, however, may reflect only the experience of those most successful at losing weight. CONCLUSIONS: Attempted weight loss is a common behavior, regardless of age, gender, or ethnicity, and weight loss goals are substantial; however, obesity remains a major public health problem in the United States. PMID- 1503168 TI - Intestinal parasites among North Carolina migrant farmworkers. AB - OBJECTIVES: The public health significance of intestinal parasitism among migrant farmworkers has been poorly defined. We report a three-part study in which we attempted to provide population-based estimates and identify risk factors for infection. METHODS: Parasite prevalence and incidence were estimated from two cross-sectional studies and a longitudinal study. We used questionnaires and clinical measurements such as hematocrits to examine risk factors and health effects. RESULTS: In the 1987 convenience sample (n = 265), parasite prevalence ranged from 28% among the US born to 86% among the Central American born, with no significant difference between the prevalence of pathogens among US-born (14%) and Mexican-born (24%) subjects (P = .12, chi 2 test). High prevalences were also found in the 1988 random sample. An annual incidence of 9.5% (n = 74) was demonstrated in 1988. Symptoms such as abdominal pain were associated with infection, and lower hematocrits were associated with hookworm infection (P = .02, t test). CONCLUSIONS: Infection with intestinal parasites appears to be an occupational hazard of farmwork, necessitating improved working and living conditions and greater clinical awareness. PMID- 1503169 TI - Restricted activity days among older adults. AB - OBJECTIVES: The number of restricted activity days experienced by an individual in the course of a year is an important measure of functional well-being, particularly for older adults. We sought to determine multivariate associations between restricted activity days and various health conditions. METHODS: We used data from the 1984 Supplement on Aging of the National Health Interview Survey to estimate the relationship between restricted activity days and age, gender, and the presence or absence of selected chronic conditions and falls for all noninstitutionalized people aged 65 years and over. Chronic conditions and falls accounted for most of the variance in the model. RESULTS: Of an annual average of 31 restricted activity days, 6 days were associated with falls; 4 days with heart disease; 4 days with arthritis and rheumatism; 2 days each with high blood pressure, cerebrovascular disease, and visual impairment; and 1 day each with atherosclerosis, diabetes, major malignancies, and osteoporosis. CONCLUSIONS: These results can be used in estimating the potential impact of health promotion programs on the health status of noninstitutionalized older adults. PMID- 1503170 TI - Predictors of smoking cessation and relapse in older adults. AB - We examined longitudinal changes in smoking behavior among older adults in three community cohorts of the Established Populations for Epidemiologic Studies of the Elderly. Smoking prevalence declined from 15% at baseline to 9% during 6 years of follow-up. Annual smoking cessation and relapse rates were 10% and less than 1%, respectively. Interval diagnosis of myocardial infarction, stroke, or cancer increased subsequent smoking cessation but not relapse. Although smoking cessation around diagnosis is increased, primary prevention could yield greater benefits. PMID- 1503171 TI - The Tobacco Institute's "It's the Law" campaign: has it halted illegal sales of tobacco to children? AB - A survey of tobacco retailers was conducted to evaluate the efficacy of the Tobacco Institute's "It's the Law" program, which has the goal of eliminating the illegal sale of tobacco to minors. Only 4.5% (7) of the 156 retailers surveyed were participating in the "It's the Law" program. Eighty-six percent of the retailers who were participating in the program were willing to illegally sell cigarettes to children, compared with 88% (131/149) of the retailers who were not participating. PMID- 1503172 TI - Homosexual and bisexual men's perceptions of discrimination in health services. AB - Questionnaires were distributed to homosexual and bisexual male participants in the Multicenter AIDS Cohort Study and to homosexual and bisexual male patients with acquired immunodeficiency syndrome (AIDS) to determine whether the men believed they had been refused medical or dental treatment because of their sexual orientation or a condition related to the human immunodeficiency virus (HIV). Men with AIDS were significantly more likely (18%) to report being refused treatment by a doctor or dentist on the basis of a known or suspected HIV-related condition than were men who were seropositive (5%) or seronegative (1%). Significantly more respondents reported refusal of dental care than of medical care. PMID- 1503173 TI - Making human junk: child labor as a health issue in the Progressive Era. AB - The adverse health effects of work on approximately 2 million employed children troubled many in the United States during the early 20th century. Advocates of reform initially built a rationale for protective legislation primarily from informal, lay observations of the broad developmental outcomes of premature employment. In this endeavor, they projected a dismal scenario of impending national deterioration. This argument received strong criticism for the inadequacy of its corroborating evidence. In response, Progressive reformers emphasized the specific, measurable consequences of particular occupations. Increasingly, liberal advocates of the exclusion of boys and girls from the work force drew upon statistical compilations of occupational injuries and illnesses diagnosed by physicians. Despite their turn toward scientism, Progressives remained somewhat ambivalent about the sufficiency of quantitative data alone to achieve their aims. PMID- 1503174 TI - Declining child mortality rates in Nicaragua. PMID- 1503175 TI - Intimidation of CTR-funded scientists claimed. PMID- 1503176 TI - Mass media as drug users' key information source on overdoses. PMID- 1503177 TI - Trend in suicide rates since fluoxetine introduction. PMID- 1503178 TI - Native American vs all-races infant mortality. PMID- 1503179 TI - Head and neck injuries from 1990 Illinois tornado. PMID- 1503180 TI - Subpopulation differentials in STD transmission. PMID- 1503181 TI - Prevalence of human T cell lymphotropic virus types 1 and 2 (HTLV-1/2) in selected Tijuana subpopulations. AB - To assess the prevalence of human T cell lymphotropic virus type 1 and 2 (HTLV 1/2) infections among potentially high-risk populations in the city of Tijuana, Mexico, the prevalence of specific antibodies was determined and information on risk behaviors was obtained between June and October 1988. The study involved 631 presumably healthy individuals, randomly selected from a study population recruited sequentially from prisoners, prostitutes, and injecting drug users (IDUs), and randomly from homosexual and bisexual men. The presence of HTLV-1/2 antibodies was determined by enzyme immunoassay and an immunofluorescence method, and positive reactions were confirmed by a radioimmunoprecipitation assay and Western blot. The prevalence of HTLV-1/2 was 2% (2 of 105) among prostitutes, 7% (29 of 410) among prisoners, 1% (1 of 105) among homosexual/bisexual men, and 21% (22 of 106) among IDUs. To properly identify the specific HTLV type, a subsequent sample of 41 imprisoned IDUs were voluntarily and anonymously recruited in June 1990 and asked to donate 20 ml of whole blood. Twenty-two percent (9 of 41) were serologically positive for HTLV-1/2, and polymerase chain reaction analysis performed on peripheral blood mononuclear cells identified HTLV-2 as the specific virus prevalent in this group. Two individuals were positive for human immunodeficiency virus type 1 (HIV-1). One of these individuals was coinfected with HTLV-2.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1503182 TI - The impact of human immunodeficiency virus infection on the epidemiology and treatment of Trypanosoma brucei gambiense sleeping sickness in Nioki, Zaire. AB - To determine if there is an association between human immunodeficiency virus type 1 (HIV-1) infection and Trypanosoma brucei gambiense sleeping sickness, all incident cases of trypanosomiasis and a control group of blood donors presenting to the same rural hospital in Zaire were tested for anti-human immunodeficiency virus type 1 (anti-HIV-1) antibodies. There was no significant difference in the prevalence of HIV-1 infection between the two groups (7 of 220, [3.2%] for the incident cases and 8 of 388 [2.1%] for the blood donors; P = 0.56). Among the three HIV-1 seropositive incident cases of trypanosomiasis treated with difluoromethylornithine, two (67%) relapsed after treatment compared with four of 39 (10%) HIV-1 seronegative incident cases treated with the same drug (P = 0.05). These findings suggest that at the present time, HIV-1 infection is not having a significant impact on the incidence of T. brucei gambiense sleeping sickness in rural Zaire, but the possibility that incident cases of trypanosomiasis concurrently infected with HIV-1 may be at higher risk of treatment failure warrants further investigation. PMID- 1503183 TI - Quantification of Rickettsia australis. AB - Several assay systems were compared for measuring the concentration of viable Rickettsia australis, including embryonated eggs, tissue cultures, and mouse inoculation. Direct rickettsial counts that included the enumeration of both viable and nonviable rickettsiae were used to obtain baseline values. Assays were conducted in parallel using serially diluted R. australis preparations to establish which assay displayed the greatest sensitivity and reproducibility. Overall, the plaque assay using buffalo green monkey kidney cells with centrifugation of the rickettsiae onto the monolayers was the most sensitive assay for detecting R. australis, while the embryonated egg assay and mouse lethality titrations were the least sensitive. PMID- 1503184 TI - Microepidemiology of onchocerciasis in Guatemala: dispersal and survival of Simulium ochraceum. AB - Wild Simulium ochraceum females, both blood engorged and non-blood engorged, were collected from human volunteers infected with Onchocerca volvulus, marked with fluorescent dyes, and released from the same locality as they were collected during February and March 1989. A small hyperendemic village located within 0.5 km of streams supporting large populations of S. ochraceum larvae served as the site for both collection and release of adult females. Fifteen sites for the recapture of flies were located within this same village, within two other villages located 1.0 and 3.7 km from it, and at other places spaced approximately 0.25-3.5 km within a coffee agroecosystem. Flies from both groups were recaptured at distances ranging to 3.5 km from the point of release. Non-blood-engorged flies, however, exhibited a greater tendency to disperse away from the release site. Of the total number of blood-engorged flies recaptured, 51.9% were collected at the release point, 25.7% at 1.0 km, and 1.6% at 3.3-3.5 km. The corresponding percentages for non-blood-engorged flies were 26.9%, 40.4%, and 4.4%, respectively. No flies from either group were recaptured at the most distant site, a large village that was 3.7 km away. Marked flies from both groups were recaptured 12-14 days after release, which was sufficient time for the development of infective O. volvulus larvae. A survival rate (4.7%) of marked, blood-engorged flies over the second and third gonotrophic cycles was estimated from the slope of the regression line of the log number of flies recaptured.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1503185 TI - Ivermectin: reduction in prevalence and infection intensity of Onchocerca volvulus following biannual treatments in five Guatemalan communities. AB - Residents of five hyperendemic communities located in the central focus of onchocerciasis in Guatemala were treated with ivermectin (Mectizan) or placebo every six months for 30 months. The effects of treatment on prevalence and the intensity of skin infection (microfilarial skin density [MFD]) were evaluated. Significant and persistent reductions in both of these indices were achieved by coverage of 80.7% of the eligible populations. The highest proportionate reductions in both indicators of infection occurred after the first treatment, followed by more gradual decreases through the fourth treatment. In one community in which the mean coverage was 92.7%, prevalence decreased from 74.0% at pretreatment to 34.9% after four treatments, while the MFD decreased from 7.8 to 2.0; reductions of 52.8% and 74.3% from pretreatment values, respectively. In every ivermectin-treated community except one, in which drug acceptance was low, the mean community MFD values were reduced to the level associated with low infectiousness for the vector, Simulium ochraceum. Moreover, the category of MFD associated with high vector infectiousness was reduced at least ten-fold over the pretreatment level. One community had low participation during the first two treatments (32.8% and 22.7% of those eligible). This increased to 55.2% at the third treatment because of implementation of an educational program describing both the disease and the beneficial effects of ivermectin and because skin biopsies and nodulectomies were not performed. Secondary reaction rates for all communities were 29.5%, 9.9%, 10.3%, 8.2%, and 7.1% for the first through fifth treatments, respectively. Pruritus was the most common (34.0%) secondary reaction, followed by facial edema (31.8%). All reactions were classified as mild to moderate. Recommendations for mass distribution of ivermectin in Guatemala are given. PMID- 1503186 TI - The effects of repetitive community-wide ivermectin treatment on transmission of Onchocerca volvulus in Guatemala. AB - The effects of biannual ivermectin treatment at the community level on transmission of Onchocerca volvulus during the dry season were measured over a 30 month period in Guatemala. In the Los Tarrales Transmission Zone, an area encompassing three villages, significant changes occurred in both the prevalence and quantity of infection in the Simulium ochraceum vector population. These included a 76% reduction in females with infective stage larvae (L3S) and an 80% reduction in number of L3S per 1,000 parous flies. Significant reductions in both the mean infective biting density (IBD) and mean transmission potential (TP) also occurred. In Santa Emilia, the prevalence of infection with L3S in S. ochraceum was significantly reduced by 77% from the baseline value. The number of O. volvulus L3S per 1,000 parous flies was also reduced by 92%. Changes in both the IBD and TP were substantial but not significant due to the high degree of variance in the occurrence of O. volvulus L3S in the vector population. This was due, in part, to the movement of infected migrant workers into the finca (coffee farm). In Los Andes, four recurrent treatments successfully blocked transmission of infective stage larvae. Prevalence (flies with all stages of developing larvae) in the vector population was reduced by 89% over the two-year period; yearly reductions in both the IBD and TP were also highly significant, ultimately ending in zero values. This finding is particularly striking since prior to treatment, Los Andes exhibited the highest IBD of the three study locations and the second highest TP. PMID- 1503187 TI - Nonvascular delivery of Rift Valley fever virus by infected mosquitoes. AB - To determine whether virus-transmitting mosquitoes inoculate infectious particles extravascularly or directly into the vascular system, we permitted mosquitoes infected with Rift Valley fever virus to feed on the distal third of the tails of suckling mice. Amputation of the distal half of the tail within 5 min after their being bitten significantly increased mouse survival as compared with that of mice whose tails remained intact. Even when tails were amputated 10 or more min after mosquito feeding, the median time to death was significantly longer in the group with the amputated tails (53.5 hr) than in those mice with intact tails (46.0 hr). Mouse survival did not correlate with ingestion of blood by the infecting mosquito. We conclude that mosquitoes inoculate virus extravascularly, rather than directly into the vascular system, when feeding on a vertebrate host. Such extravascular delivery of virus by a transmitting mosquito may affect viral pathogenesis, antiviral activity, and vaccine efficacy. PMID- 1503188 TI - Ingestion of Plasmodium falciparum sporozoites during transmission by anopheline mosquitoes. AB - We investigated the process of sporozoite transmission during blood feeding for Anopheles gambiae and An. stephensi experimentally infected with Plasmodium falciparum. When infective mosquitoes were fed 22-25 days postinfection on an anesthetized rat, sporozoites were detected in the midgut of 96.5% of 57 An. gambiae (geometric mean [GM] = 32.5, range 3-374) and in 96.2% of 26 An. stephensi (GM = 19.5, range 1-345). There were no significant differences between species either in salivary gland sporozoite loads or in the number of ingested sporozoites. There was a significant linear relationship between sporozoite loads and the numbers of ingested sporozoites for both An. gambiae (r = 0.38) and An. stephensi (r = 0.69). Subsequently, An. gambiae were tested for sporozoite transmission by allowing them to feed individually on a suspended capillary tube containing 10 microliters of blood. A total of 83.3% of 18 infective mosquitoes transmitted a GM of 5.9 (range 1-36) sporozoites. The same mosquitoes contained a GM of 23.4 (range 2-165) ingested sporozoites. The number of ingested sporozoites was related to sporozoite loads (r = 0.42) but not to the number of sporozoites ejected into capillary tubes. Ingested sporozoites remained in the midgut up to 10 hr after feeding. The comparable numbers of sporozoites ingested by infective mosquitoes in both experiments indicates that the actual number of sporozoites transmitted to the vertebrate host during blood feeding is significantly reduced by the blood ingestion process.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1503189 TI - Ultrasonographic changes of the liver in Schistosoma haematobium infection. AB - Abdominal ultrasonographic examination was performed in 61 hospitalized patients with chronic liver diseases and 253 school children from a village endemic for Schistosoma haematobium and were compared with 142 urban children without exposure to Schistosoma. The prevalence of ultrasound-detectable hepatomegaly and splenomegaly and the degree of periportal fibrosis was compared between those with and without S. haematobium infection. Among 13 patients with biopsy-proven schistosomal hepatic fibrosis, three with coarse changes secondary to S. mansoni infection showed grade III periportal fibrosis, while 10 patients with fine schistosomal hepatic fibrosis due to S. haematobium had borderline (two) or grade I (eight) changes. Ultrasound evidence of periportal fibrosis was not detected in patients with hepatic cirrhosis, chronic active hepatitis, or fatty infiltration. However, three of 14 patients with chronic persistent hepatitis had grade I periportal fibrosis and two had borderline changes. The frequency of ultrasound detected hepatomegaly and splenomegaly was greater among rural S. haematobium infected children (35.2% and 22.4%, respectively) than among noninfected rural (21.1% and 13.3%) and urban (16.9% and 4.9%) children. Also, the frequency of grade I periportal fibrosis was significantly greater (P less than 0.01) in S. haematobium-infected children (22.4%) than in noninfected rural (11.7%) and urban (0.7%) children. No patients with S. haematobium infections, either in the hospital or the village, had grade II or III periportal fibrosis.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1503191 TI - Evidence that both normal and immune elimination of Schistosoma mansoni take place at the lung stage of migration prior to parasite death. AB - The number and distribution of autoradiographic foci observed in this and previous studies following percutaneous infection with 75Se-labeled Schistosoma mansoni cercariae indicate that the lungs are the principal site of worm elimination in both normal mice and mice immunized with irradiated cercariae. It was observed in the present study, however, that the intensities of the autoradiographic foci produced in the lungs during both the normal (early) and immune (late) phases of elimination were identical to those of foci produced in the livers of the same mice by larvae shown to be alive. In contrast, foci produced in the lungs by heat-killed, intravenously injected, lung schistosomula became smaller and fainter with time, disappearing completely between seven and 10 days after injection in normal mice and between four and six days in immunized mice. These results indicate that although the targets of both normal and immune elimination do not proceed beyond the lung stage of migration, they do not die in the lungs. A possible explanation for this paradoxical situation, for which there is some experimental evidence, is that unsuccessful migrators leave the blood stream, enter alveoli, pass up the trachea, and are eventually digested in the gastrointestinal tract or eliminated from the body intact. PMID- 1503190 TI - Combined microautoradiographic and histopathologic analysis of the fate of challenge Schistosoma mansoni schistosomula in mice immunized with irradiated cercariae. AB - Combined microautoradiographic and histopathologic methods were used to locate and examine schistosomula of Schistosoma mansoni in the lungs of irradiated cercaria-immunized mice 21 days after percutaneous challenge infection with 75Se labeled cercariae. Of 75 schistosomula examined in serial sections, 53% were located in the pulmonary microvasculature, 23% in alveolar spaces, 3% with one end in a vessel and the other in an alveolar space, and the locations of 21% were not identified. Inflammatory reactions of variable intensity were observed around schistosomula in both vascular and alveolar sites, although the most intense category of reactions was associated almost entirely with alveolar larvae. All autoradiographic foci contained recognizable schistosomula. Although the concentration of reduced silver grains precluded cyto-structural analysis, observations on schistosomular contour and shape provided no evidence of larval damage. Our findings suggest that immune elimination of schistosomula in mice immunized with irradiated cercariae is partly or largely effected by a process of alveolar extrusion of viable parasites during their lung migration. PMID- 1503192 TI - Carditis in Lyme disease susceptible and resistant strains of laboratory mice infected with Borrelia burgdorferi. AB - The clinical and pathologic evolution of cardiac Lyme disease was evaluated in four-week-old susceptible C3H/He (C3H) and resistant C57Bl/6 (B6) mice on days 3, 6, 10, 15, 30, 60, and 90 after intradermal inoculation with Borrelia burgdorferi strain N40. Culture, DNA polymerase chain reaction, in situ nucleic acid hybridization, immunoperoxidase histochemical analysis, and silver stain were used to detect spirochetes. Spirochetes were first detected by culture on day 6 in two of four C3H mice. The hearts of all mice of both genotypes were culture positive by day 10 and infection persisted through day 90. The spirochetes had a predilection for connective tissue in the heart base, especially around the aorta, epicardium of the upper ventricles and atria, myocardial interstitium, and endocardium. Carditis was first detectable on day 10, reaching a maximum severity on day 15, then resolved, except for persistence of periaortic lymphoplasmacytic infiltrates through day 90 in C3H mice and through day 60 in B6 mice. The C3H mice developed more severe disease than the B6 mice, and this was associated with the earlier appearance, greater numbers, and later clearance of spirochetes in C3H mice. Electrocardiographs of infected and control mice revealed bradycardia and tachycardia in many C3H mice, but in very few B6 mice. Serum creatinine phosphokinase levels did not become elevated at any interval. PMID- 1503193 TI - Pathology of falciparum malaria in Vietnam. AB - Autopsy samples from the brains of 20 patients who died of falciparum malaria were examined by light microscopy and by an immunohistologic method. Particular attention was paid to a comparison of the pathologic features of the white matter and the cortex. In the high-sequestration (greater than 50%) group (n = 8), the mean +/- SD percentage of cerebral microvessels that showed parasitized red blood cell (PRBC) sequestration was 71.2 +/- 8.1% in the cortex and 84.0 +/- 6.7% in the white matter. The difference in the PRBC sequestration rate between cortex and white matter was statistically significant (P less than 0.01). Perivascular and ring hemorrhages were seen more frequently in the white matter than in the cortex. Deposition of IgG and Plasmodium falciparum antigen in the cerebral microvessels was more highly significant in the white matter than in the cortex (P less than 0.01). Our study demonstrated that the localized concentration of PRBC sequestration in the brain correlated with the marked immunohistologic differences in the microvessels of cortex and white matter. PMID- 1503194 TI - Use of antibiotics for ear, nose, and throat disorders in pregnancy and lactation. PMID- 1503195 TI - The management of epistaxis. PMID- 1503196 TI - Cochlear microphonics recorded from fetal and newborn sheep. AB - PURPOSE: Sounds present within the uterus stimulate the fetal inner ear and central auditory pathway. This study was undertaken to determine the efficiency of transmission of exogenous airborne stimuli to the fetal inner ear. In this way, we may quantify the extent to which the fetal auditory system is isolated from sounds produced outside the mother. MATERIALS AND METHODS: Cochlear microphonics were recorded from fetal and newborn sheep to evaluate the extent to which the fetus is isolated from sounds exogenous to the ewe. Electrodes were surgically placed in contact with the round window membrane in nine near-term fetal sheep. Cochlear microphonics were recorded in response to 1/3 octave-band noises (0.125 to 2.0 kHz) delivered through a loudspeaker 1.8 m from one side of the pregnant ewe. Sound pressure levels generated by the noises were simultaneously recorded ex utero with a microphone and in utero with a hydrophone previously sutured to the fetal neck. After cochlear microphonic amplitudes were recorded, the fetus was delivered through an abdominal incision. Recordings were repeated from the newborn lamb. Fetal sound isolation was calculated as the difference between the sound pressure levels that were necessary to evoke equal cochlear microphonic amplitudes from the fetus and from the newborn lamb. RESULTS: The sound attenuation observed was variable for all frequencies. The fetus was isolated from external sounds by 11.1 dB for 0.125 kHz, 19.8 dB for 0.25 kHz, 35.3 dB for 0.5 kHz, 38.2 dB for 1.0 kHz, and 45.0 dB for 2.0 kHz. CONCLUSIONS: Other investigators have demonstrated that the immature auditory system is more susceptible to damage produced by noise exposure than is the mature auditory system. Low-frequency noise produces damaged cells that later in life code higher frequencies. A possibility of fetal hearing loss produced by intense noise exposure needs more careful evaluation. PMID- 1503197 TI - Bone conduction thresholds in patients with otosclerosis. AB - PURPOSE: Sensorineural hearing loss in patients with otosclerosis is commonly encountered. This study was conducted to determine if surgery on the otosclerotic ear had an effect on the sensorineural hearing. METHODS: A cohort of 262 patients subjected to operation in 311 ears were evaluated. All patients had a minimum of 5 years follow-up and patients over 60 years of age were excluded. Audiograms obtained 1 day before surgery were compared with those obtained 1 year postoperatively and at the last follow-up examination in the study. Results were evaluated using the Student's t test for statistical analysis of hearing results. RESULTS: The mean follow-up was 9.6 years. Deterioration of bone conduction scores occurred in 6.4% of 311 operated ears. Deterioration of bone conduction threshold occurred in the speech frequency in 6 ears (1.9%). CONCLUSIONS: Bone conduction scores of operated ears remained quite stable compared with the otosclerotic ears not subjected to operation. Patients with bilateral otosclerosis may benefit from surgery performed on both ears when indicated. PMID- 1503198 TI - Postsurgical mucocele. PMID- 1503199 TI - Malignant (atypical) carcinoid of the larynx occurring in a patient with laryngotracheal papillomatosis. PMID- 1503200 TI - Metastatic squamous cell carcinoma to the temporal bone. PMID- 1503201 TI - Nasal dilator for management of sleep apnea. PMID- 1503202 TI - Basal cell carcinoma with matrical differentiation. AB - Three cases of basal cell carcinoma showing shadow cells within basaloid islands have been described using the term basal cell carcinoma with matrical differentiation for this histologic variant. We present four new cases of basal cell carcinoma with evidence of matrical differentiation. Unlike the cases previously published, these lesions showed nests of shadow cells either within the lobules of basaloid cells or forming nests in the stroma. We also noted the presence of a foreign body reaction and calcification. These neoplasms illustrate the capability of basal cell carcinoma to differentiate toward hair matrix cells. Basal cell carcinoma with matrical differentiation must be added to the uncommon variants of basal cell carcinoma showing adnexal differentiation. A parallel between the degrees of differentiation of the cutaneous sebaceous neoplasms with those showing matrical differentiation is proposed. PMID- 1503203 TI - Bullous lesions in acrodermatitis enteropathica. Histopathologic findings regarding two patients. AB - Acrodermatitis enteropathica (AE) is an autosomic recessive disorder affecting early infancy. Two cases of infantile AE with low plasma zinc levels are reported in which unusually prominent bullous and vesicobullous lesions were seen on the hands and feet, in addition to the more typical erythematous and scaly patches. Both psoriasiform and bullous lesions responded dramatically to oral zinc-sulfate supplementation. The histopathologic features of the bullous lesions of AE have not previously been fully examined. Histologically, the bullous lesions were characterized by intraepidermal vacuolar changes with massive ballooning, leading to intraepidermal vesiculation and blistering, with prominent epidermal necrosis and with no acantholysis. The bullous lesions did not arise on erythematous patchy lesions, but developed ex novo on unaffected skin. The histopathologic differential diagnosis with other bullous conditions is discussed. PMID- 1503204 TI - Segmental lentiginosis with "jentigo" histologic pattern. AB - We report a case of segmental lentiginosis (unilateral lentiginosis), that is, asymmetric distribution of lentigines on one side of the body, in a 23-year-old woman. Lesions involved the right side of the face and the cervical region, mostly within the area of division of the trigeminal nerve. Histologic examination disclosed a lentiginous pattern as well as some nests of melanocytes at the dermal-epidermal junction (so-called jentigo pattern). Similar cases have been described in the literature under the term "zosteriform lentiginous nevus," which in our opinion makes for confusion since the same term has also been used to describe cases that fit the diagnostic criteria for speckled lentiginous nevus (nevus spilus). PMID- 1503205 TI - Pigmented trichoblastoma. AB - We report a case of trichogenic tumor with epithelial and mesenchymal components recapitulating the formation of hair germs. The epithelial lobules were highly pigmented and affected the full thickness of the dermis, extending into the subcutaneous fat. In addition, amyloid deposits were found within the epithelial lobules and in the stroma. The overall architecture was reminiscent of hair bulbs. Problems of differential diagnosis with other trichogenic tumors and pigmented tumors are discussed. PMID- 1503206 TI - Making sense of the dysplastic nevus controversy. A unifying perspective. AB - There is currently much confusion regarding the "dysplastic nevus." There is justification for this confusion, given the abundance of seemingly contradictory statements in the literature. This article proposes a unifying perspective that can help reconcile seemingly contradictory statements and decrease confusion regarding the "dysplastic nevus." The proposed unifying perspective suggests that the "dysplastic nevus" does not exist in nature as a distinct clinical-pathologic entity, but that there is probably legitimacy to the concept of a "dysplastic nevus." PMID- 1503208 TI - Rapid whitening of the hair first reported in the Talmud. Possible mechanisms of this intriguing phenomenon. AB - The first reported episode of rapid whitening of the hair is recorded in the Talmud. This intriguing phenomenon is explained on the basis of a two-step process. The first step involves the actual abrupt development of white hair due to vitiligo or alopecia areata. The second step involves the apparent sudden whitening of the scalp hair due to either simultaneous lengthening of the white hair or selective loss of the dark hair. In fact, the hair that is perceived as suddenly whitening was already white. PMID- 1503207 TI - A critical analysis of textbooks of dermatopathology in historical perspective. Part 2. PMID- 1503209 TI - Doctor, I'm [sic]. PMID- 1503210 TI - Early melanoma--histologic terms. PMID- 1503211 TI - Early melanoma. PMID- 1503212 TI - Temperature dependence of retention in reversed-phase liquid chromatography. 1. Stationary-phase considerations. AB - The retention mechanism in reversed-phase liquid chromatography (RPLC) has been investigated by examining the temperature dependence of retention, with emphasis on the role of the stationary phase in the retention process. Both chromatographic temperature studies and differential scanning calorimetry were used to examine the role of alkyl chain bonding density on the retention mechanism in RPLC. Phase transitions of reversed-phase stationary phases were observed at bonding densities greater than 2.84 mumol/m2. Thermodynamic constants for the transfer of a solute from the mobile phase to the stationary phase (delta H degrees and delta S degrees) were calculated for low bonding density columns, and comparison of these values to previously reported values for the partitioning of a nonpolar solute from the bulk organic liquid to water indicated that the chromatographic retention process is not well-modeled by bulk-phase oil-water partitioning processes. In addition, this data showed that the entropic contribution to retention becomes more significant with respect to the enthalpic contribution as the stationary-phase bonding density is increased, providing additional support that partitioning, rather than adsorption, is the relevant model of retention. PMID- 1503213 TI - Temperature dependence of retention in reversed-phase liquid chromatography. 2. Mobile-phase considerations. AB - The retention mechanism in reversed-phase liquid chromatography (RPLC) has been examined over a wide temperature range with emphasis on the role of the mobile phase. van't Hoff plot shapes were used to assess the retention mechanism, and the data showed evidence of the hydrophobic effect when water-rich and/or hydrogen-bonded mobile phases such as methanol/water were used. However, different van't Hoff plot shape was observed with acetonitrile/water mobile phases, indicating a change in the retention mechanism. These data showed that the hydrophobic effect, which had previously been proposed as the driving force for retention, is not a satisfactory explanation for the retention process in all RPLC systems. PMID- 1503214 TI - Experimental evaluation of the separation efficiency in capillary electrophoresis using open tubular and gel-filled columns. AB - The band dispersion phenomena in capillary zone electrophoresis (CZE) using untreated and surface-treated open tubular and gel-filled capillaries were experimentally evaluated, with emphasis on small capillary diameters (10-100 microns). Laser-induced fluorescence detection was used for high-sensitivity detection of the isoindoles originated from model amino acids. The plots of plate height vs electric field strength were generated for different column radii and compared with a theoretical model for CZE. In addition to the diffusion controlled band dispersion in the relatively low electric field range, adsorptive interactions between a solute and the capillary wall may play a certain role in band-broadening. The sorption-desorption kinetics become important with increasing electric field strength. Thermal effects appear to contribute little to band-broadening in relatively small capillaries (less than 50-microns i.d.) within normal operating voltages (less than 30 kV), but could become significant in capillaries with larger bores (greater than 75-microns i.d.). With gel-filled capillaries of small diameters (less than 50-microns i.d.), diffusion processes can be minimized. In addition, thermal effects do not appear critical in such columns at reasonable voltages. PMID- 1503215 TI - Sequential injection immunoassay utilizing immunomagnetic beads. AB - A novel sequential injection immunoassay (SIIA) method is described which utilizes immunomagnetic beads to investigate short-time antibody binding. The method is versatile and flexible and may therefore be adapted to many different applications. Initial results for a competitive assay are also presented. The immunomagnetic bead reactor is created within the flowing stream by retaining immunomagnetic beads with an electromagnet to form an open tube reactor. Thus, the spent beads may be discharged after each analysis. This eliminates the problems of instability of reaction surfaces and eliminates the need for additional time traditionally required for regeneration of the solid-reacting phase in order to not only save time and increase sampling frequency but also to provide each individual sampling cycle with a fresh, uniform portion of beads. The spent beads are collected off line and may be regenerated later. Short-time binding kinetic studies demonstrate linear initial binding under 1 min, which then begins to reach saturation in approximately 10 min. Competitive binding assays of monoclonal mouse IgG (MRC OX-19) to polyclonal sheep anti-mouse IgG immobilized to the immunomagnetic beads show reproducible linear displacement in 30-120-s reactions. Fluorescence detection is utilized with a detection limit of 155 ng/mL, and since the reaction time is typically 2 min or shorter, the sampling frequency is 30 samples/h. PMID- 1503216 TI - Performance characteristics of a composite multivariate quality control system. AB - We present the results of an evaluation of the performance characteristics of a composite multivariate quality control (CMQC) system that incorporates quality control rules for univariate, multivariate, and correlation conditions. The CMQC system evaluated is designed to help analysts detect unacceptable trends and systematic error in one or more variables, unacceptable random error in one or more variables, and unacceptable changes in the correlation structure of any pair of variables. It is also designed to be tolerant of missing data, to allow analysts to reject as few as one or as many as all variables in a run, and to provide analysts with control statistics and graphics that logically relate to sources of analytical error. We show that the various components of the CMQC system have adequate statistical power to detect systematic errors, random errors, and correlation changes under the conditions likely to be encountered with multivariate analytical measurement systems: (1) a single variable with increased systematic or random error; (2) all variables or a subgroup of variables affected by a common problem that increases systematic or random error; and (3) missing data for one or more variables in a run. We also show that the power of the multivariate component of the CMQC system to detect systematic and random errors is higher than the power of an alternative multivariate test criterion. PMID- 1503217 TI - Multiwavelength thermal lens spectrophotometer based on an acousto-optic tunable filter. AB - The instrumentation development of a novel, all solid-state, nonmoving parts, fast-scanning and wide-tuning range multiwavelength thermal lens spectrophotometer based on the acousto-optic tunable filter (AOTF) is described. Initially, the essential electronic driver was developed to facilitate the systematic characterization of the paratellurite (TeO2) AOTF and to demonstrate that this filter can be successfully and uniquely used as an all solid-state, nonmoving parts dispersive device to rapidly diffract white incident light into a selected color beam, to amplitude modulate the diffracted monochromatic light, and to keep its intensity constant. The multiwavelength thermal lens instrument was subsequently constructed using this AOTF, and preliminary results on advantages of this spectrophotometer such as its ability to characterize trace chemicals and to analyze multicomponent samples are delineated. PMID- 1503218 TI - Liquid sample injection using an atmospheric pressure direct current glow discharge ionization source. AB - An atmospheric pressure DC glow discharge in helium has been used as an ionization source for organic samples introduced by liquid injection into atmospheric pressure ionization mass spectrometry (API/MS). The glow source operates typically in the range up to 1 mA of current at less than 1 kV, although the source can be operated up to a discharge current of 10 mA. Even at the high current used in this work, the protonated molecule, MH+, is observed with little or no fragmentation for many of the samples studied. The detection limits achieved for API glow discharge detection are typically in the low femtomole region for small organic molecules including small biological neurotransmitters, drugs, pesticides, phenylthiohydantoin-substituted amino acids, and explosives. A detection limit of approximately 2 pg has been achieved for tyramine with linear quantitation over at least 3 orders of magnitude. The sensitivity in these experiments has been further improved by optimization of the skimmer-interface system and the liquid injection/nebulization design. PMID- 1503219 TI - Characterization of N-linked oligosaccharides by electrospray and tandem mass spectrometry. AB - Electrospray and tandem mass spectrometry are used to characterize underivatized oligosaccharides that have been digested from asparagine side chains of glycoproteins. Oligosaccharides that contain sialic acids were detected with the best sensitivity in the negative-ion detection mode whereas those that do not contain sialic acid were detected with the best sensitivity in the positive-ion detection mode. The positive-ion abundances of oligosaccharides were greatly enhanced in electrospray mass spectra by adding 10 mM sodium acetate or ammonium acetate to the sample solvent. Tandem mass spectrometry was used to determine primary structural features of the oligosaccharides. Methodology that has been developed on branched high-mannose, hybrid, and complex carbohydrate standards was applied to a mixture of oligosaccharides that were digested with N-glycanase from the glycoprotein, ovalbumin. The composition and relative abundances of individual oligosaccharides obtained from the electrospray mass spectrum compare favorably to those obtained by anion-exchange chromatography/pulsed amperometric detection and by gel permeation chromatography of the oligosaccharides after radiolabelling the reducing end of the carbohydrates. The oligosaccharide content of ovalbumin was independently determined from the heterogeneity observed in the electrospray mass spectrum of the intact 44-kDa glycoprotein. Comparison of the oligosaccharide compositions determined before and after enzymatic digestion shows a selective digestion of high-mannose and low molecular weight oligosaccharides by N-glycanase. PMID- 1503220 TI - Collisional activation with random noise in ion trap mass spectrometry. AB - Random noise applied to the end caps of a quadrupole ion trap is shown to be an effective means for the collisional activation of trapped ions independent of mass/charge ratio and number of ions. This technique is compared and contrasted with conventional single-frequency collisional activation for the molecular ion of N,N-dimethylaniline, protonated cocaine, the molecular anion of 2,4,6 trinitrotoluene, and doubly pronated neuromedin U-8. Collisional activation with noise tends to produce more extensive fragmentation than the conventional approach due to the fact that product ions are also kinetically excited in the noise experiment. The efficiency of the noise experiment in producing detectable product ions relative to the conventional approach ranges from being equivalent to being a factor of 3 less efficient. Furthermore, discrimination against low mass/charge product ions is apparent in the data from multiply charged biomolecules. Nevertheless, collisional activation with random noise provides a very simple means for overcoming problems associated with the dependence of single-frequency collisional activation on mass/charge ratio and the number of ions in the ion trap. PMID- 1503221 TI - Enantiomeric separations using bovine serum albumin immobilized on ion-exchange stationary phases. AB - Bovine serum albumin (BSA) can be readily immobilized on ion-exchange stationary phases by frontal analysis of a proper solution. This provides a simple means of adjusting the amount of BSA contained in the column and of measuring it accurately. Although the immobilization is ionic and not covalent, the columns are stable for extensive periods of time. If needed, they can be easily regenerated by the same frontal analysis procedure. PMID- 1503222 TI - Analyses, risks, and authoritative misinformation. PMID- 1503223 TI - Analytical chemistry--feeding the environmental revolution? PMID- 1503224 TI - Theoretical and experimental investigation of steady-state voltammetry for quasi reversible heterogeneous electron transfer on a mercury oblate spheroidal microelectrode. AB - A mercury microelectrode formed by electroreduction of mercury on an inlaid gold microdisk is experimentally shown to be well modeled by oblate spheroidal geometry when the ratio of the semiminor axis to the semimajor axis of the protruding drop is less than 1. The validity of the geometry is established by comparison of the experimentally determined coefficient in the steady-state diffusion current equation with the theoretical value for oblate spheroidal geometry. Spherical cap geometry is also shown to be an equally valid geometric model; however, theoretical treatment for this system is more difficult. The theory of a quasi-reversible electrode process is developed and applied to the determination of the electrode parameters of the RuIII(NH3)6/RuII(NH3)6 electrode reaction on a mercury oblate spheroidal microelectrode. Results agree well with others found in the literature for the same process on a mercury electrode. PMID- 1503226 TI - Matrix-assisted laser desorption mass spectrometry of proteins isolated by capillary zone electrophoresis. AB - A simple method for the off-line coupling of laser desorption mass spectrometry (LDMS) and capillary zone electrophoresis (CZE) is described. Representative mass spectra of subpicomole quantities of proteins isolated from CZE are presented and discussed. The current detection limit for bovine alpha-lactalbumin is 100 fmols injected onto the CZE column. Horse heart myoglobin was demonstrated to be stable in CHES/KCl, a CZE buffer, for at least 1 month, suggesting that some isolates can be safely stored for long time periods prior to LDMS analysis. Protein stability in 0.1% aqueous trifluoroacetic acid (TFA), a common solvent for LDMS, must also be considered. In the special case of porcine pepsinogen, significant (greater than 50%) degradation was observed within 5 min in TFA. In favorable cases, mass measurement accuracies of +/- 0.02% were obtained for protein isolates. Factors limiting mass measurement accuracy are presented. Finally, the possibility of identifying protein isolates, by combining N-terminal sequencing, molecular mass measurements, and selective peptide "mapping" procedures, is discussed. PMID- 1503225 TI - Determination of lysergic acid diethylamide (LSD), iso-LSD, and N-demethyl-LSD in body fluids by gas chromatography/tandem mass spectrometry. AB - Procedures for detection and quantitation of lysergic acid diethylamide (LSD), iso-LSD, and N-demethyl-LSD by capillary chromatography/tandem mass spectrometry (GC/MS/MS) are presented. Several methods for derivatization, sample introduction, and ionization, in combination with mass spectrometry/mass spectrometry (MS/MS), have been evaluated for overall ionization efficiency and product-ion sensitivity and specificity. Fragmentation pathways derived from low energy collision-induced dissociation (CID) spectra of protonated LSD, and the protonated trimethylsllyl derivatives of LSD (LSD-TMS) and deuterium-labeled analogs of LSD, have been proposed. Principal dissociations primarily involve the amide and piperidine-ring moieties in which losses of CH3 radical, CH3NH2, CH3NCH2, diethylamine, diethylformamide, and N,N-diethylpropenamide from MH+ are observed. Positive-ion ammonia chemical ionization and subsequent MS/MS analysis of the protonated molecules (MH+) of the trimethylsilyl (TMS) derivatives of LSD, iso-LSD, and N-demethyl-LSD provide a high degree of specificity for identification of these compounds in urine or blood at low-pg/mL concentrations. Negative-ion chemical ionization and GC/MS/MS analysis of the molecular anion (M ) of the trifluoroacetyl (TFA) derivative is well suited for trace-level identification of N-demethyl-LSD, a metabolite of LSD. PMID- 1503227 TI - Conformational effects in the reversed-phase chromatographic behavior of recombinant human growth hormone (rhGH) and N-methionyl recombinant human growth hormone (Met-hGH). AB - This paper examines the retention behavior of recombinant DNA-derived human growth hormone (rhGH) in reversed-phase chromatography and its separation from the closely related N-methionyl variant (Met-hGH). It is first shown that retention for rhGH decreases with increasing column temperature when 1-propanol (1-PrOH) is used as organic modifier. On the other hand, retention increases with temperature when acetonitrile (CH3CN) is employed. The differences in behavior for the two organic modifiers could be related to conformational changes in the protein as determined by solution and adsorption intrinsic fluorescence spectroscopy. Specifically, desorption and elution of rhGH using 1-PrOH could be correlated with a solvent-induced conformational change, with retention decreasing with increasing temperature due to the increasing ease of structural alteration. On the other hand for CH3CN the increase in retention correlated with temperature rise was related to a partial structural change yielding a more hydrophobic species. In this case, a surface-driven process is suggested. The work then turned to the separation of rhGH and Met-hGH where it was found for both organic modifiers optimum separation occurred at 45 degrees C and pH 6.5. Separate studies revealed that during the conformational change Met-hGH appeared more hydrophobic than rhGH since protein-protein aggregation was observed at a lower 1-PrOH concentration. It is suggested that this hydrophobic difference, which was optimized under the conditions cited above, resulted in the separation. The study demonstrates the importance of conformational changes in retention behavior and separation of protein samples. PMID- 1503228 TI - Flow injection spectrophotometric determination of calcium, phosphate and chloride ions in milk. AB - Flow injection procedures for the determination of calcium, phosphate and chloride ions in milk samples are described. The reactions are based on the formation of coloured complexes and their spectrophotometric monitoring. A sample pre-treatment with acetate buffer was carried out owing to the complexity of the sample matrix. For chloride, a rapid and reliable automated procedure for direct measurement of its content in milk (using a dialyser to eliminate interferences) is also described. After optimizing the sample pre-treatment and flow injection variables, the procedures were applied to commercial milk; the results obtained agreed satisfactorily with those of the reference methods. With 50 mm3 samples, a working range of 0-15 ppm for calcium, 50-150 ppm for phosphate and 5-100 ppm for chloride is covered with a precision of better than 1.1%. The sample throughput was higher than 50 samples h-1. These preliminary experiments are the basis for the automation of the determination of calcium, phosphate and chloride ions using a computer-controlled, self-designed and laboratory-built autoanalyser. PMID- 1503229 TI - Spectrofluorimetric flow injection method for the individual and successive determination of L-cysteine and L-cystine in pharmaceutical and urine samples. AB - A flow injection configuration is proposed for the determination of L-cysteine and L-cystine individually and for mixtures of both analytes. The procedure is based on the rapid oxidation of L-cysteine by thallium(III) with concomitant formation of fluorescent thallium(I). The inclusion of a selecting valve and of a copper-coated cadmium column in the configuration allows the successive determination of two analytes. Linear calibration graphs were obtained between 5 x 10(-6) and 5 x 10(-5) mol dm-3 of L-cysteine and between 2 x 10(-6) and 2 x 10( 5) mol dm-3 of L-cystine. The applicability of the method to the determination of L-cysteine and L-cystine in pharmaceutical preparations was demonstrated by investigating the effect of potential interferents and by the analysis of commercial preparations. The method was successfully applied to the determination of L-cysteine and L-cystine in urine samples. PMID- 1503230 TI - Enzymic method for the spectrophotometric determination of choline in liquor. AB - A sensitive spectrophotometric method for the determination of choline in liquor is described. The method involves the conversion of choline into formaldehyde by sequential enzymic reactions (choline oxidase and catalase), followed by the formation of a chromophore with 4-aminopent-3-en-2-one. The calibration graph was linear in the range 0.4-15 micrograms cm-3 of choline. The relative standard deviation at 5 micrograms cm-3 of choline was 1.3%. There was no interference from most of the common ingredients of liquor. More than 95% of choline added at two levels was recovered from real samples. The method is simple, and the detection limit was 2 micrograms g-1 when 5 g of sample were assayed. PMID- 1503231 TI - Behaviour of long-lived Chernobyl radionuclides in a soil-water system. AB - Field and laboratory experiments have been used to study the behaviour of long lived radionuclides in the zone affected by the Chernobyl accident. Speciation of 90Sr and 137Cs in soils and bottom sediments was determined. The principal distinction of the Chernobyl fallout was that it contained a relatively small proportion of exchangeable forms because a considerable fraction of the radionuclides was incorporated as part of the insoluble fuel particles. Disintegration of fuel particles in soils and bottom sediments results in transition of non-exchangeable forms into exchangeable forms. Radionuclide species have different pathways and rates of migration in soils and bottom sediments. Migration of each chemical form was described by a convective dispersive equation taking into account transformation processes of radionuclide species in soils or bottom sediments. Adsorption of 90Sr and 137Cs in the environment is controlled by the cation-exchange capacity and the selectivity of the solid phase (i.e., soil, bottom sediments and suspended matter) and the cationic composition of the liquid phase (i.e., soil solution, surface run-off and river or lake water). The corresponding parameters for the processes were obtained. PMID- 1503232 TI - Cholesterol immobilization via ether-linked sepharose gels. AB - Cholesterol has been immobilized on Sepharose-6B via oxyether linkages to the 3- or 25-position. The 3- or 25-hydroxysterol methanesulfonates were coupled with epoxy-Sepharose-6B at 80 degrees C for 24 h. Approximately 2% of the ligand was incorporated into the gel. These types of affinity columns may be useful in purifying proteins that specifically bind or metabolize cholesterol. PMID- 1503233 TI - Determination of blood lead in dried blood-spot specimens by Zeeman-effect background corrected atomic absorption spectrometry. AB - A simple procedure for the determination of blood-lead levels in dried blood-spot filter-paper specimens is described. A 3/16 inch dried blood spot was analysed by a method involving extraction of the lead into 1.25% (NH4)2HPO4-0.5% Triton X-100 solution. A matrix-based calibration was used for analysis, with use of a Zeeman effect background corrected atomic absorption spectrometer. The within-run precision (% relative standard deviation) of the method at the low end of the analytical range was 19% at 0.36 mumol dm-3 and 14% at 0.60 mumol dm-3. The accuracy of the method was verified by recovery tests and by comparison with a routine whole-blood method. The mean blood lead level of 425 Toronto newborns was 0.19 mumol dm-3 (range 0-0.75 mumol dm-3). PMID- 1503234 TI - Arsenic speciation by ion chromatography with inductively coupled plasma mass spectrometric detection. AB - Four As compounds were successfully separated and detected by single-column ion chromatography with inductively coupled plasma (ICP) mass spectrometric detection. The mass spectral interferent ArCl+ was reduced by chromatographically resolving chloride from the negatively charged arsenic species. Determination of four As species was investigated in urine, club soda and wine. Detection limits of 0.16 ng of As(III), 0.26 ng of As(v), 0.073 ng of dimethylarsinic acid (DMA) and 0.18 ng of methylarsonic acid (MMA) in wine were obtained. Sensitivity was further improved by using an He-Ar mixed gas ICP as the ionization source. However, the intensity of the ArCl+ interference was also increased using this plasma. Detection limits of 0.063 ng of As(III), 0.037 ng of As(v), 0.032 ng of DMA and 0.080 ng of MMA in club soda were achieved using the He-Ar plasma source. Similar limits of detection were found in urine and wine. PMID- 1503235 TI - High-performance liquid chromatographic and derivative ultraviolet spectrophotometric determination of amoxycillin and dicloxacillin mixtures in capsules. AB - Two rapid assay procedures based on high-performance liquid chromatography (HPLC) and derivative ultraviolet (UV) spectrophotometry have been developed for the simultaneous determination of amoxycillin and dicloxacillin in two-component capsule formulations. The HPLC determination was carried out on a reversed-phase C8 column with use of a mobile phase consisting of methanol-0.02 mol dm-3 ammonium acetate (pH 5) (50 + 50) at a flow rate of 1.0 cm3 min-1, with UV detection at 230 nm. The fourth-derivative spectrophotometric procedure depends on the measurement of the derivative amplitudes, in 0.1 mol dm-3 NaOH, at 308.5 and 275 nm for amoxycillin and dicloxacillin, respectively. For both procedures, the calibration graphs were linear in the ranges 20-200 and 20-140 micrograms cm 3 for the HPLC and UV derivative methods, respectively, with an almost zero intercept and a correlation coefficient of 0.999. Commercial capsules and laboratory-prepared mixtures containing both penicillins in different proportions were assayed by the developed procedures. The results were of comparable accuracy as indicated by a statistical analysis of the data, using both t- and F-tests. PMID- 1503236 TI - [The preservation of the whole corpse with natural color]. AB - An especially low-odor embalming technique was developed over a 30-years-period using a total of 977 complete cadavers, numerous cadavers after autopsy, and in vitro series of fresh beef. The color, consistency, and transparency of the tissue were very well preserved. The technique met high standards of preservation without releasing harmful substances into the environment. Concentrations of formaldehyde in room air remained under the limit of detection by Drager capillaries. The efficacy for disinfection of the method was confirmed by bacteriologic tests. None of the cadavers or samples developed molds. PMID- 1503237 TI - [An arterial substance for subsequent injection during the preservation of the whole corpse]. AB - Masses for arterial injection were evaluated in 360 whole cadavers that had been injected with preservation fluid. A mass consisting of dextrin, latex, and lead tetroxide produced the best results. This mass provided high radiopacity at large distances from the injection site and ideal firmness for dissection. The easy application of the mass makes it suitable for research purposes as well as for teaching dissections. PMID- 1503238 TI - [Synovial recesses and bursae of the lumbosacral joint]. AB - There are four types of cavities of the lumbosacral joints. Type A: The synovial membrane is all around attached to the margin of the articular facet of the superior articular process of the sacrum. Type B: The synovial membrane extends to the posterior surface of the sacrum forming a recess at the root of the superior articular process; this recess communicates widely with the cavity of the joint. Type C: The synovial membrane also forms a recess similar to that of type B, but the gap of communication is narrowed by a fibro-adipose meniscoid. Type D: The synovial membrane is attached in the same way as described in type A; besides a synovial bursa non communicating with the cavity is found at the root of the superior articular process. We have found 43% showing type A, 33% type B, 16% type C and 8% type D. The recesses and bursae described above enable the inferior articular process of the fifth lumbar vertebra to slide at the posterior surface of the sacrum, thus avoiding a painful rubbing during dorsiflexion of the lumbar spine. The existence of these sliding facilities does not depend on the range of the lumbosacral angle nor on the quality of the lumbosacral intervertebral disc. PMID- 1503239 TI - [The olfactory region of the bat Scotophilus heathi. Light and electron microscopic studies]. AB - The present investigation reports light and electron microscopical aspects of the main olfactory epithelium (MOE) of the insectivorous bat Scotophilus heathi. Serial frontal sections of the nose and associated structures reveal: 1) that the MOE is located on most of the ethmoturbinals and on the proximal upper portion of the nasal septum; and 2) that the vomeronasal organ is absent in this species. The ultrastructure of the MOE of Scotophilus heathi is similar to that observed in other vertebrates. Moreover, we did not observe significant morphological differences between the MOE of male and female animals. Nevertheless, the supra nuclear region of the supporting cells of males and females shows a different amount and distribution of "lysosome-like" cell organelles at the two times of the year investigated. PMID- 1503240 TI - Endothelial cell helix in small arterioles of human ureters. A study by scanning electron microscopy (SEM). AB - Microvessel corrosion casts of human ureters were prepared. Portions of casts were longitudinally cut by use of a pulsed Eximer laser beam in order to get insight into microvessel branches studied in SEM. Larger arterioles (greater than 30 microns in diameter) showed oval imprints of endothelial cell nuclei along the vessel axis. Imprints were found in furrows parallel to resin ridges. Smaller arterioles (less than microns in diameter) displayed imprints of nuclei aligned in a helix around the vessel axis. With regard to capillaries, one nucleus imprint was spaced far apart from the other. Venules demonstrated a reticular network of thick, attenuated resin ridges and of small meshes which consisted of round or oval nucleus imprints. It is concluded that smaller arterioles form an endothelial cells helix. PMID- 1503241 TI - [The lateral articular surface of the medial cuneiform bone facing the intermediate cuneiform bone]. AB - 300 medial cuneiform bones were examined to explore the different forms of the joint surface on the lateral side of the bone facing the intermediate cuneiform bone. This joint surface consists of two parts, a proximal one and a dorsal one. The proximal part is orientated dorsoplantarally. At its proximal margin there exists a tight contact with the proximal joint surface for the navicular bone. The dorsal part is sited at the dorsal margin of the lateral side of the bone. Different forms of fusion of these part could be seen. In 62.67% they show tight confluence. In 17.67% the fusion is limited to a slight contact. In the rest, 19.67%, there exists no contact between these two parts. These forms correlate to the proximal height of the bone. A large proximal height extends the degree of separation of the dorsal joint surfaces (consisting of the dorsal section of the proximal part and the whole dorsal of the joint surface for the intermediate cuneiform bone as well as the joint surface for the second metatarsal bone). Therefore these joint surfaces are split to their components. PMID- 1503242 TI - [The nomenclature of the blood vessels of the kidney]. AB - The differing interpretations of the course of the renal artery-branches possibly are caused by the Nomina Anatomica. The course of the branches of the renal artery is described and based upon this less misleading names for these branches are suggested. PMID- 1503243 TI - An anatomical investigation of the muscles of the pelvic outlet in Japanese giant salamander (Cryptobranchidae Megalobatrachus japonicus) with special reference to their nerve supply. AB - Four pelvic halves from two Japanese giant salamanders (Cryptobranchidae Megalobatrachus japonicus, one male and one female) were dissected in order to obtain detailed morphological data on the lumbosacral plexus and the muscles of the pelvic outlet. According to the positions of the passage of the metazonal nerves, the nerves can be divided into three groups: 1) the nerves passing dorsal to the caudofemoralis muscle, 2) the nerves passing between the caudofemoralis and the caudoischiadicus, 3) the nerves passing ventral to the caudoischiadicus. In consideration of the sites of origin from the lumbosacral plexus, a three-way stratificational analysis can be made, group 1 arising craniodorsal to group 2, and group 3 caudoventral to group 2. It is suggested that the three pelvic outlet muscles, the caudofemoralis, caudocruralis, and caudoischiadicus, have derived from the ventral muscles of the posterior limb, and have extended ventrocaudalwards. PMID- 1503244 TI - Microvascular pattern during the growth of regenerating muscle fibers in the rat. AB - Quantitative methods were used to analyze changes in the capillarization of skeletal muscle during regeneration. The H-E staining technique was used to establish three arbitrary stages of fiber regeneration on the basis of qualitative histological evaluation. ATPase and light microscopic techniques were used to calculate capillary density, the number of capillaries surrounding each fiber, and the fiber area served by each capillary, for each of the three stages established. The results obtained indicated variations in the vascularization of regenerating fibers from one stage of maturity of another: capillarization was greater in the initial stages of regeneration, returning gradually to normal values by the final stages of the process. Interestingly enough the pattern in the capillarization of skeletal muscle during regeneration seems to be similar to that taking place during postnatal muscle development. Both processes appear to be governed by the increase in fiber size. PMID- 1503245 TI - [The effect of cyclooxygenase inhibitors on the course of hereditary retinal dystrophy in RCS rats]. AB - Daily administration of acetyl salicylic acid (ASA) and ibuprofen leads to an appreciable retardation in the process of retinal degeneration in the RCS rat which is dependent on the dosage given. The photoreceptor cell nuclei and inner segments are relatively well preserved in all regions of the retina. While the outer nuclear layer of 32 day old RCS rats is usually composed of only 3-4 rows, we found 8-9 nuclear rows exhibiting minimal pyknotic change in animals which had been treated with higher doses of ASA. These differences in layer thickness could be confirmed using morphometric analysis. The outer segments show evidence of degenerative change although they are in a clearly better condition than those found in untreated animals and in those animals treated at lower dose. Phagolysosomal structures which are not otherwise apparent in this strain of rat are detected only in the RPE cells of animals treated with higher dose. The animals treated with ibuprofen show essentially the same morphological changes although a corresponding effect in regard to the thickness of the outer nuclear layer was only achieved after a high dose. The determined dose for the optimal preservation (thickness) of the outer nuclear layer lies around 160 mg/kg body weight for acetyl salicylic acid and at 400 mg/kg body weight for ibuprofen. PMID- 1503246 TI - The circulus arteriosus cerebri in the guinea pig. AB - Arteries to the brains of guinea pigs were injected with latex and the circulus arteriosus cerebri was studied. Most of the arterial blood to the guinea pig brain came from the internal ophthalmic and vertebral arteries. The internal carotid arteries were extremely thin. In addition to an anastomosis that was found between the right vertebral and the basilar arteries in one specimen, the right vertebral artery anastomosed with the left vertebral artery in eight specimens and in one animal the basilar artery was double along a major part of its length. PMID- 1503247 TI - The connective tissue sheath of uterus and vagina in the human female fetus. AB - A morphological study concerning the development and arrangement of the connective tissue surrounding uterus and vagina was performed by investigating epoxy resin impregnated sections through the pelves of 9-37-week-old female fetuses, of newborn children and a three-year-old child. In order to study the histology of the connective tissue in detail paraffin, semithin and ultrathin sections were used. The organization of the pelvic connective tissue in female fetuses can best be studied in middle-aged fetuses (19-28 weeks of gestation). We here report that no supportive ligaments of the uterus are found in fetuses of that age group, but that the connective tissue covering uterus and vagina is part of the connective tissue sheaths of neighbouring structures. The fetal uterus is interposed between dense subperitoneal connective tissue circularly covering the vesico- and rectouterine pouch. Dorsally the subperitoneal tissue of the rectouterine pouch joins the circularly arranged connective tissue of the rectal adventitia. A triangularly-shaped plate of dense connective tissue is situated at each lateral border of the cervix uteri. Dorsally it is continuous with the circularly running fibres of the rectouterine pouch. Whereas the dorsal wall of the vagina is loosely connected with the rectal adventitia, fibrous connective tissue intimately fuses the muscular wall of the vagina with that of the neck of the bladder and of the urethra. No evidence is provided for the existence of smooth muscle cells and elastic material within the connective tissue covering the fetal uterus. PMID- 1503248 TI - The sperm penetration test (P-test) can predict fecundability in the male partner from infertile couples. AB - Three hundred and twenty-one consecutive couples were investigated for infertility at Hvidovre University Hospital in the period from November 1977 to June 1985. The male partners were evaluated in two ways: the classical semen analysis, and the ability of sperm to penetrate fresh hen egg white, the P-test. A Cox regression analysis was used to describe the relation between these variables and fecundability, i.e. the time required to conceive. Four of thirteen variables--the number of morphologically normal spermatozoa, the number of motile spermatozoa, the P-test, and the man's age--each have significant relation to the fecundability. However, when covariation is considered, only the P-test and the man's age possess significant prognostic information, whereas the variables of the classical semen analysis do not. This indicates that the P-test may replace the classical semen analysis when trying to predict individual pregnancy probabilities. Finally, the P-test and the man's age are combined to form a prognostic index which predicts the fecundability of the male partner in the individual infertile couple. PMID- 1503249 TI - Use of an ATP-supplemented medium for the conservation of human semen and the effect of caffeine on the motility of preserved sperm. Results in artificial insemination. AB - Human semen can be preserved at 4 degrees C in an artificial medium containing 15% ATP-MgCl2 for up to 5 d. This method has been applied to samples from subjects with either normal or abnormal semen. After the conservation period the recovery of sperm motility observed was good when low doses of caffeine (3.5 or 7.0 mM) were added. PMID- 1503250 TI - Intra-uterine insemination with prepared sperm vs. unprepared first split ejaculates. A randomized study. AB - In this randomized prospective study, we determined the conception rate following intra-uterine insemination with washed and prepared sperm, or with the first portion of a split ejaculate, in couples with longstanding male (n = 27, 70 treatment cycles) or cervical infertility (n = 14, 29 treatment cycles). Folliculogenesis and ovulation were induced by human menopausal gonadotropin and human chorionic gonadotropin. Significantly more couples conceived in the male infertility group following intra-uterine insemination with washed sperm, than after intra-uterine insemination with split ejaculate (9 vs. 2; P less than 0.05), while no difference in pregnancy rate (2 vs. 2) was found by the two intra uterine insemination methods in the cervical infertility group. PMID- 1503251 TI - Effect of different types of textile fabric on spermatogenesis. I. Electrostatic potentials generated on surface of human scrotum by wearing different types of fabric. AB - This paper comprises a study of the electrostatic potentials generated on the surface of the scrotal area when different types of textile fabric were worn. 21 healthy volunteers were divided into 3 equal groups. The first group was dressed in underpants made of 100% polyester, the second of 100% cotton, and the third of a 50:50% polyester:cotton mixture. With an electrostatic kilovoltmeter, the electrostatic potentials were measured 1 h after wearing the pants once at daytime and a second time at night. The test was repeated 4 times, each on a separate day. No electrostatic potentials were detected on the cotton underpants. The polyester pants showed the highest potentials (mean 338.9 +/- 25 SD Volt cm 2) while the mixed polyester:cotton pants produced less than half that level (mean 148.3 +/- 16 SD Volt cm-2). The readings at daytime were higher than at night, probably due to the higher temperature during the day. The accumulated electrostatic charges on the pants are due to the friction of the pants with the skin. As a result of friction, equal and opposite charges are accumulated on the skin surface and on the inner surface of the pants facing the skin. Eventually, an 'electrostatic field' is produced traversing the scrotal contents and may disturb the testicles and/or epididymis leading to disordered spermatogenesis. PMID- 1503252 TI - Loss of acid phosphatase from rat spermatozoa as a method for assessing the acrosome reaction. AB - A method is presented for evaluating the extent of the acrosome reaction by measuring the release of acrosomal acid phosphatase from rat spermatozoa during incubation under capacitating conditions. Treatment of spermatozoa with lysophosphatidylcholine or Triton X-100 released the acid phosphatase from the sperm cell. Using this enzymatic method we could not detect an alteration in enzyme activity following 5 h incubation under capacitating conditions. The effect of in vitro capacitation for 5 h in the absence or presence of heparin or ionophore A23187 was studied. Incubation in the presence of heparin (10 micrograms ml-1) caused a 32% increase in enzyme activity. After exposure of the spermatozoa to ionophore A23187 (0.5 microM) 16% increase of enzyme activity could be detected. PMID- 1503253 TI - The effect of clomiphene citrate and its Zu or En isomers on the reproductive system of the immature male rat. AB - The effect of clomiphene citrate (CC) and of its Zuclomiphene (ZuC) and Enclomiphene (EnC) isomers on the reproductive organs of immature male rats under different experimental conditions is reported. CC, ZuC, and EnC were administered daily to groups of either intact or castrated rats between the age of 21-44 d. This led to inhibition of weight increase of testis and accessory glands in the intact group. Spermatogenesis was arrested at the stage of primary spermatocyte following CC and ZuC treatment, and at the stage of young spermatids by EnC treatment. In the castrated group clomiphenes significantly stimulated weight increase of seminal vesicles (SV) compared with castrated control animals, but the former group were unable to achieve organ weight gain comparable to that in normal controls. Administration of human Chorionic Gonadotropin (hCG) together with CC or each of its isomers to intact animals, abolished the drug effect on spermatogenesis and on reproductive organ growth. Administration of CC, ZuC, and EnC together with testosterone to castrated animals, abolished the drug effect on growth inhibition of accessory glands. In intact treated rats LH and testosterone secretion were suppressed by all forms of clomiphenes. In the castrated group ZuC proved to be the most potent inhibitor of LH secretion. Therefore, it is inferred that ZuC and EnC have different potencies as far as their biological activity in the immature male rat is expressed. PMID- 1503254 TI - Bovine epididymal sperm proacrosin-acrosin system: quantification and partial characterization. AB - Several studies suggest that acrosin, an acrosomal trypsin-like serine proteinase, plays a role in fertilization. The enzyme is present in an enzymatically inactive precursor form, called proacrosin and is believed to be converted to the enzymatically active form(s) through one/multiple physiological event(s) prior to the sperm penetration of the zona pellucida. Although, the proacrosin-acrosin system of several species has been well documented, the study of the enzyme system in bovine caput and cauda epididymis (where the maturation of spermatozoa occurs) has not been characterized. The present study demonstrates the quantification and partial characterization of the proacrosin-acrosin proteinase system in unpurified acrosomal extracts of bovine caput and cauda epididymal sperm. Proacrosin activation followed the sigmoidal type of activation curve. Activation experiments demonstrate that almost 80-90% of this protein exists in zymogen (proacrosin) form either in ejaculated or caput and cauda epididymal spermatozoa. Time-course activation studies showed that the zymogen in isolated spermatozoa was completely converted to active non-zymogen form in 3 and 5 h after removal from the cauda and caput regions, respectively, at pH 8.0 at 25 degrees C. This conversion was markedly inhibited by calcium in a dose dependent manner and the inhibition was reversible. On the other hand, calcium has a stimulatory effect on the hydrolytic activity of acrosin. These studies reveal that the proacrosin-acrosin system can be identified in crude extracts of bull epididymal and ejaculated sperm. PMID- 1503255 TI - Evolutionary genetics of ruminant lysozymes. AB - Comparative studies of mammalian lysozymes and their genes have contributed to knowledge of how new functions arise during evolution. The recruitment of lysozymes for functioning in the stomach fluid of ruminants has occurred in response to selection pressures that are partly known and on a time-scale that is known. A semiquantitative analysis of adaptive evolution is thus made possible by the ruminant lysozyme system. Large-scale production of lysozyme by the stomach lining entailed gene duplication as well as a change in gene expression. Remoulding of the lysozyme for working and lasting in the stomach fluid involved accelerated amino acid replacements, which may have been facilitated by intergenic recombination. The possibility that multigene families can accelerate adaptive evolution, by virtue of their capacity for bringing together functionally coupled substitutions, receives emphasis in this review. PMID- 1503256 TI - Bivariate flow cytometry of farm animal chromosomes: a potential tool for gene mapping. AB - Bivariate flow karyotypes of chromosomes from sheep, cattle and pig lymphocytes and from a cattle-mouse somatic cell hybrid line were obtained using a dual laser fluorescence-activated cell sorter (FACS). Pig chromosomes were resolved into 19 20 peaks, indicating that most, if not all, pig chromosomes could be separated by this technique. Sheep chromosomes showed incomplete separation but three clear peaks, presumably representing the three large metacentric chromosomes, plus five other clusters were obtained. Cattle chromosomes showed poor separation but about four peaks could be distinguished, indicating that certain chromosomes could be sorted in this species. The use of cattle-mouse hybrids may enable other individual cattle chromosomes to be obtained. It is concluded that FACS separation will be a useful additional tool for gene mapping. PMID- 1503257 TI - Identification of the major histocompatibility complex in the ring-necked pheasant, Phasianus colchicus. AB - Reciprocal immunization between parents of an Illinois family of ring-necked pheasants, Phasianus colchicus, resulted in antisera detecting two pairs of alloantigens segregating among 13 progeny. The four alloantigens were tentatively designated as 1 and 2, transmitted antithetically by the sire, and 3 and 4, transmitted antithetically by the dam. Genetic segregation occurring in second generation progeny demonstrated that these two pairs of antigens belonged to a single genetic system. This alloantigen system was shown to correspond serologically to the major histocompatibility complex (MHC) of the chicken by cross-reactivity of the antigens of this system with specific subregional chicken MHC reagents, appropriately absorbed with erythrocytes of individual pheasants. These four haplotypes of the pheasant MHC were subsequently designated as MhcPhco B1, MhcPhco-B2, MhcPhco-B3 and MhcPhco-B4. Traditional immunogenetic analysis of 30 pheasant families produced in this study disclosed a minimum of 14 pheasant haplotypes of this alloantigen system (MHC) to be segregating in the population under evaluation. PMID- 1503258 TI - Numerical variation of nucleolar organizer regions after silver staining in domestic and wild Suidae (Mammalia). AB - Selective silver staining was used to investigate the cellular distribution of numbers of nucleolar organizer regions (NORs) in domestic pigs (Sus scrofa) of eight different breeds, the European wild boar (S. scrofa scrofa), Indonesian wild boar (S. scrofa vittatus), Javan warty pig (S. verrucosus), Sulawesi warty pig (S. celebensis), and pigmy hog (S. salvanius). In the domestic pig as well as in the wild (sub)species of Sus, actively transcribing ribosomal RNA genes were found to be present in the secondary constrictions of chromosome pairs 10 and 8. Chromosomes 10 were consistently Ag-positive. Chromosomes 8 less frequently showed Ag-NORs, resulting in different mean numbers of Ag-NORs per individual animal. Mean Ag-NOR numbers per breed or (sub)species were generally higher in the wild representatives of Sus than in the domestic breeds. The highest mean numbers of Ag-NORs were observed in the Meishan breed and in S. celebensis and S. salvanius. The Meishan breed appears to be conservative in Ag-NOR staining pattern, being more comparable to the Asian wild Suidae than to the European breeds. PMID- 1503259 TI - Cloning and sequencing of the porcine lactoferrin cDNA. AB - cDNA clones encoding the entire porcine lactoferrin protein were isolated and sequenced. The porcine lactoferrin cDNA sequence presented here is 2259bp in length and encodes a leader peptide of 19 amino acids and a mature protein of 684 amino acids. Comparisons with other lactoferrins indicate a single glycosylation site. The iron- and anion-binding sites, and the cysteine residues involved in disulphide bonds, are conserved between the lactoferrin proteins. PMID- 1503260 TI - Sequence of porcine beta-lactoglobulin cDNA. AB - cDNAs encoding porcine beta-lactoglobulin were isolated and sequenced. The porcine beta-lactoglobulin cDNA is 768bp in length and encodes a pre-protein of 178 amino acids. One additional cDNA clone was found to encode an additional amino acid (lysine) in the mature protein. PMID- 1503261 TI - Assignment of the porcine tumour necrosis factor alpha and beta genes to the chromosome region 7p11-q11 by in situ hybridization. AB - The loci of the porcine tumour necrosis factor genes, alpha (TNFA) and beta (TNFB), have been chromosomally assigned by radioactive in situ hybridization. The genomic probes for TNFA and TNFB yielded signals above 7p11-q11, a region that has been shown earlier to carry the porcine major histocompatibility locus (SLA). These mapping data along with preliminary molecular studies suggest a genomic organization of the SLA that is similar to that of human and murine major histocompatibility complexes. PMID- 1503262 TI - Nucleotide sequence of the second exon of a BoLA-DQB gene. PMID- 1503263 TI - Demonstration of serum albumin (ALB) polymorphism in wild rabbits, Oryctolagus cuniculus, by means of isoelectric focusing. AB - Genetic polymorphism of serum albumin was demonstrated by isoelectric focusing in wild rabbit populations from Portugal and England. Gene frequencies were estimated to be (1) ALB*1 = 0.47, ALB*2 = 0.49, ALB*3 = 0.04, in Portugal, and (2) ALB*1 = 0.60 and ALB*2 = 0.40, in England. One hundred Portuguese domestic rabbits of mixed breeds were all of ALB 1 type. PMID- 1503264 TI - A new genetic variant Z2 in the Pi system of horses. AB - A new genetic variant in the horse Pi system, designated Z2, was reported in Polish Arabs by using two-dimensional agarose polyacrylamide gel electrophoresis. The frequencies of Pi alleles F, G, L, L2, N, S, U, W, Z and Z2 were found to be 0.036, 0.005, 0.171, 0.013, 0.008, 0.237, 0.416, 0.003, 0.107 and 0.004 respectively. PMID- 1503265 TI - The sequence of porcine alpha s1-casein cDNA: evidence for protein variants generated by altered RNA splicing. AB - A cDNA library was constructed from mRNA isolated from lactating porcine mammary gland and screened with a bovine alpha s1-casein cDNA clone. Three classes of cDNA isolated varied in the number of bases within the coding region. The full length porcine alpha s1-casein cDNA is 1124bp and codes a preprotein of 206 amino acids. The other two classes of alpha s1-casein cDNA lacked 18bp and 60bp respectively when compared to the 1124-bp cDNA sequence. PCR amplification confirmed the presence of these sequences in total RNA. These differences appear to be due to altered RNA splicing. PMID- 1503266 TI - A TaqI polymorphism at the ovine beta A-inhibin (INHBA) locus. PMID- 1503267 TI - A MspI polymorphism at the ovine thyroxine binding globulin locus (TBG). PMID- 1503268 TI - Detection of leucochimaerism in bovine twins by DNA fingerprinting. AB - Karyotyping and hypervariable genetic markers indicate extensive leucochimaerism between pairs of dizygotic twins in cattle, a result of placental vascular anastomosis. The extent of this chimaerism includes both kind and number of cells exchanged. All heterosexual twin pairs harboured two types of leucocytes, having either XX or XY chromosome pairs, and 30 of 31 pairs of twins shared identical DNA fingerprints. Although chromosome results from skin fibroblasts indicate that some chimaerism occurs in the skin, the low level allows for differentiation of genotypes between twins. The results warrant against the common practice of using blood samples for DNA typing if twinning is not properly documented. PMID- 1503269 TI - Genetic polymorphism of plasminogen and vitamin D binding protein in red deer (Cervus elaphus L.). AB - Genetic polymorphism was detected in the red deer (Cervus elaphus L.), plasma proteins, plasminogen (PLG) and vitamin D binding protein (GC) using antiserum to human proteins. The affinity of the antisera to deer plasma was less than 10% that of a human standard but they bound specifically to proteins of molecular weight expected for GC and PLG. Three codominant alleles of GC and five of PLG were observed. In a set 124 farmed deer calves and their parents, six calves had genotypes which were not consistent with the expectations of inheritance. Further inconsistencies were found when variation in isocitrate dehydrogenase (IDH) and transferrin (TRF) was examined. Using genetic models which included pedigree error parameters the data were shown to be consistent with genetic inheritance of all loci in a data set containing approximately 4.8% (SE 1.4%) parent-progeny pedigree mismatches. In samples from four deer populations representative of the red deer introduced to New Zealand the GC and PLG polymorphisms provided a probability of paternity exclusion (PE) of between 0.34 and 0.54 and when IDH and TRF were also included the PE was between 0.46 and 0.66. The four populations differed significantly in allele frequency, which supports historical evidence that they originate from separate introductions of small numbers of European red deer. PMID- 1503270 TI - Canine plasma alkaline phosphatase polymorphism and its relationship with the canine Tr blood group system. AB - A canine blood group antigen, QN, which was detected by a naturally occurring alloantibody in the antiglobulin test, was shown to be antigenically related to the human A and cattle J antigens by absorption experiments. Family studies supported a dominant mode of inheritance with the gene controlling the production of QN being dominant to the gene responsible for its absence. Frequencies of the QN and Tr antigens and serological data strongly suggested that the two antigens are identical. Two canine plasma alkaline phosphatase variants, F and S, were detected by starch gel electrophoresis, pH 8.65. Assuming genetic control of two codominant alleles, ALPF and ALPS, the distributions of types in families differed significantly from expectation. A relationship between the ALP and Tr(QN) systems was demonstrated with Tr-positive animals having a significant deficiency of S alkaline phosphatase types. PMID- 1503271 TI - Sheep blood polymorphism and genetic divergence between French Rambouillet and Spanish Merino: role of genetic drift. AB - Rambouillet sheep originating from Spanish Merino have been maintained in France as a small and closed flock since their importation. After 190 years of independent evolution, the flock has markedly differentiated from its Spanish parental population. The observed differences between them were characterized by the fixation in Rambouillet of the Mb and F30 alleles, which occurred in Spanish Merino with frequencies of 0.90 and 0.80 respectively (at two distinct blood group loci M and F30) and by the absence in Rambouillet of other alleles or phenogroups (at the Tf and the A, B, C blood group loci) which were observed in Spanish Merino with frequencies ranging from 0.10 to 0.28. On the basis of their phenotypic distributions at 11 blood polymorphic loci, the two populations differed significantly from each other (total chi 2 values = 352.62, 23 df, P less than 0.001). By comparing the observed magnitude of gene frequency differences between Rambouillet and Spanish Merino with the estimate of inbreeding coefficient for Rambouillet obtained from pedigrees, it appeared that the observed genetic differences could be attributed to the evolutionary change due to random drift in the small and closed flock of Rambouillet. PMID- 1503272 TI - Detection of multiple beta-casein (CASB) alleles by amplification created restriction sites (ACRS). AB - Direct sequencing of polymerase chain reaction (PCR) amplified DNA has been used to detect the DNA sequences for bovine beta-casein (CASB) A3 and B variants. Based on these sequences we have designed primers which create allele-specific restriction sites in the PCR product. Restriction analysis of PCR product generated in one reaction enable us to identify the A1, A2, A3 and B alleles of CASB rapidly without the use of radioactivity. PMID- 1503273 TI - Genetic analysis of fingerprints in Merinos d'Arles x Booroola Merino crossbred sheep. AB - The M13.13 minisatellite probe, consisting of a polymer of the M13 VNTR consensus sequence, cross-hybridized to ovine DNA and allowed detection of several polymorphic loci. Individual specific patterns were obtained in sheep using this probe. Pedigree analysis showed that individuals were heterozygous for most of the DNA fragments detected (88%). By studying the segregation of male's variable DNA fragments, a minimum of 10 loci were defined. The ovine DNA 'fingerprint' obtained with M13.13 is polymorphic enough to be used efficiently in animal identification, paternity testing, and possibly as a source of genetic markers for linkage analysis. PMID- 1503274 TI - Expression and characterization of ovine major histocompatibility complex class II (OLA-DR) genes. AB - Previous work made use of nucleic acid probes corresponding to different subtypes of the class II regions of the human and murine major histocompatibility complex (MHC) to isolate seven different alpha and 24 different beta genes of the ovine MHC from two cosmid libraries. In an attempt to identify pairs of alpha and beta genes capable of cell surface expression, all permutations of alpha and beta genes were in turn transfected into mouse L-cells. Two pairs of alpha and beta genes co-expressed and stable ovine MHC class II L-cell lines were developed. The expressed alpha genes had previously been defined as DR-alpha homologues (DRA) by differential Southern hybridization to human subtype specific class II probes. The expressed ovine beta genes were also assigned as ovine DR-beta homologues (DRB) on the basis of their sequence having a higher degree of similarity with human DRB than any other subtype. A total of eight out of 23 anti-sheep class II specific monoclonal antibodies were typed OLA-DR specific by FACScan analysis using the L-cell lines. PMID- 1503275 TI - Cloning and sequencing of the porcine kappa-casein cDNA. AB - cDNA clones encoding porcine kappa-casein were isolated and sequenced. The porcine kappa-casein cDNA is 851 bp in length and encodes a preprotein of 188 amino acids. PMID- 1503276 TI - The sequence of porcine alpha s2-casein cDNA. AB - cDNA clones encoding the entire porcine alpha s2-casein message were isolated and sequenced. The porcine alpha s2-casein cDNA is 1093 bp, excluding the poly(A) tail, in length and encodes a preprotein of 235 amino acids. PMID- 1503277 TI - The sequence of porcine beta-casein cDNA. AB - Porcine cDNAs clones encoding beta-casein were isolated and sequenced. The porcine beta-casein cDNA is 1100bp in length, excluding the poly(A) tail, and encodes a preprotein of 232 amino acids. PMID- 1503278 TI - Genetic polymorphism in sheep plasma detected using antibodies to human plasminogen. AB - Protein variation was identified in sheep when Western blots of polyacrylamide gels (routinely used to resolve transferrin polymorphism) were stained using antibodies to human plasminogen. The affinity of the antibodies to ovine plasma was less than 7% that of a human standard but they bound specifically to a single polymorphic protein. In 146 lambs and their parents the inheritance of the ovine plasminogen antigen polymorphism was consistent with four autosomal alleles segregating codominantly. However, an additional two lambs had types which were incompatible with their putative parents. The pedigrees of these lambs were tested by DNA fingerprinting and shown to have been incorrectly recorded. The genetic polymorphism detected by human plasminogen antiserum provided a probability of sire exclusion (PE) ranging from 0.04 to 0.32 and a polymorphic information content (PIC) of 0.08 to 0.50 in flocks of five sheep breeds: Perendale, Romney, Merino, Texel and Coopworth (in order of increasing genetic variation in this locus). Significant differences in allele frequency were observed between breeds but sampling did not assess the variation among flocks within a breed. PMID- 1503279 TI - Dinucleotide repeat polymorphism within the ovine major histocompatibility complex. PMID- 1503280 TI - Ovine dinucleotide repeat polymorphism at the FCB4 locus. PMID- 1503281 TI - Ovine dinucleotide repeat polymorphism at the MAF214 locus. PMID- 1503282 TI - [Clonidine premedication and isoflurane anesthesia to reduce bleeding in otologic surgery]. AB - Seventy-seven ASA 1 patients scheduled for ear surgery were premedicated orally, 90 min before anaesthesia. They were randomly assigned to two groups, according to the drug used: hydroxyzine alone (group T, n = 39) or combined with clonidine (4.9 +/- 0.3 micrograms.kg-1) (group C, n = 38). Anaesthesia was induced with midazolam (0.3 mg.kg-1) and alfentanil (30 micrograms.kg-1). Ventilation was controlled with a 50/50 v/v mixture of oxygen and nitrous oxide (FETCO2 = 4 to 4.5%), and anaesthesia was maintained with repeated injections of alfentanil (15 micrograms.kg-1 at the start of surgery, and then every 15 min) and with isoflurane (mean end-expiratory concentration 0.6 +/- 0.3 vol %). Surgical bleeding was assessed every ten minutes on a numerical scale with four values. A bloodless surgical field was obtained by adjusting the isoflurane concentration up to 2 MAC, and by using a trinitrine infusion as required. Cardiovascular monitoring included an electrocardioscope and automatic blood pressure measurements. Before induction of anaesthesia, the blood pressure was lower in group C (84.7 +/- 11.2 vs. 95.9 +/- 106 mmHg) (p less than 0.001); the difference in heart rate was not significant (65 +/- 15 vs. 70.6 +/- 14 b.min-1). Moderate stable intraoperative hypotension was obtained in both groups. However, mean arterial blood pressure (C:65.8 +/- 7.8 mmHg; T: 73 +/- 9.4 mmHg) and heart rate (C: 53.4 +/- 6.8 b.min-1; T: 60.4 +/- 8 b.min-1) were significantly lower in the patients premedicated with clonidine (p less than 0.001). There were more periods of sinus bradycardia (heart rate less than or equal to 50 b.min-1), mostly seen before the beginning of surgery, in group C patients (p less than 0.01); atropine was also required more often (when the heart rate was less than or equal to 40 b.min-1) in this group of patients (NS). The comparative assessment of surgical field quality was in favour of group C (no troublesome bleeding) as opposed to the control group (16% troublesome bleeding); there were also more bloodless surgical fields in the former group (73.7% vs. 48.7% in group T, p less than 0.05). This study therefore demonstrated that clonidine premedication before anaesthesia with isoflurane was helpful in decreasing bleeding during ear surgery. PMID- 1503283 TI - [EMLA analgesic cream for venopuncture during anesthetic induction in children]. AB - A prospective study was designed to assess the quality of skin analgesia provided by the EMLA anaesthetic cream, an eutectic mixture of local anaesthetics (prilocaine and lidocaine). The children, aged 3 months to 15 years, and scheduled for genital and urinary surgery, were allocated to two groups, those aged less than or equal to 5 years (35 +/- 14 months, n = 17), and those aged greater than 5 years (97 +/- 26 months, n = 22). The cream (1.6 +/- 0.6 g) was applied by a nurse in the ward as a thick layer on the area of skin to be anaesthetised (on the dorsum of the hand and at the elbow), and covered by a closed adhesive dressing. This required 2.6 +/- 1.7 min, and was considered to be very easy (72%) or easy (28%). The venepuncture (22 or 20 gauge catheter) was carried out by one of the seven anaesthetists of the paediatric surgical units, 92 +/- 51 min after the cream had been applied. The children aged less than or equal to 5 years complained of pain of intensity 7.5 +/- 2.2 (CHEOPS scale, range 4 to 13) and, for those aged greater than 5 years, 24 +/- 21 on a visual analogic scale (range 0 to 100). Local adverse effects occurred in ten patients (skin paleness, erythema, or both). It was concluded that EMLA cream provides convenient analgesia for venepuncture in toddlers and children. PMID- 1503284 TI - [Pharmacokinetics of methohexital given by constant rate intravenous infusion]. AB - The pharmacokinetic characteristics of a constant rate methohexitone infusion were studied in young ASA 1 patients undergoing maxillofacial surgery. They were randomly assigned to two groups; group M patients (n = 7) were given 9 mg.kg-1.h 1 of methohexitone for one hour, and group MF patients (n = 7) 9 mg.kg-1.h-1 of methohexitone with 7 micrograms.kg-1.h-1 of fentanyl, also for one hour. Blood samples for determining methohexitone concentrations were obtained at various times, from before the start of the methohexitone infusion up to 19 h afterwards. In twelve patients, a two-compartment model was appropriate to characterize the decrease of methohexitone concentration; for the other two (one in each group), a three-compartment model was applied. There were no statistically significant differences between the two groups. Elimination half-life in group M was 3.22 +/- 1.96 h, and total plasma clearance 8.54 +/- 2.8 ml.kg-1.min-1. The wide variations in pharmacokinetic parameters between subjects may explain some unpredictable variations in duration of action of methohexitone. Fentanyl did not modify methohexitone pharmacokinetics, which remained of the first order. However, it potentiated the barbiturate's action: extubation was only possible after stopping the infusion for 39.4 min +/- 22 min in group MF, and 15.4 min +/- 6 min in group M (p less than 0.01). At that time, plasma concentrations were respectively 3.12 +/- 0.99 mg.l-1 (group MF) and 5.71 +/- 2.09 mg.l-1 (group M), (p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1503285 TI - [Caudal block in children: analgesia and respiratory effect of the combination bupivacaine-fentanyl]. AB - A study of the duration of analgesia and of the respiratory response to hypercapnia was carried out in 14 children who had had a caudal block with either bupivacaine alone (group B) or combined with fentanyl (Group B+F). Fourteen ASA I or II 5 to 10-year-old children undergoing genital and urinary surgery were included. They were not premedicated. At first, general anaesthesia was induced with halothane and nitrous oxide in oxygen. Thereafter, caudal anaesthesia was then carried out with 1 ml.kg-1 of 0.25% bupivacaine with adrenaline 1 in 200,000. Group B+F patients were also given 1 microgram.kg-1 of fentanyl in 1 ml of normal saline, and those in Group B 1 ml of normal saline. The level of sensory loss on leaving the operating theatre as well as the duration of motor paralysis were monitored. Postoperative pain was scored with Hannalah and Broadman's score (0 to 10) 2, 4, 8 and 24 h after the caudal block. Respiratory rate (fR), tidal volume (VT) and minute ventilation (VE) were assessed 10 min before induction of general anaesthesia, and 30, 60 and 120 min after the caudal anaesthesia. Petco2 was also measured before induction of general anaesthesia, and 60 and 120 min after caudal anaesthesia; at the same times, the ventilatory response to hypercapnia was assessed using Read's method with a Douglas bag containing 7% CO2 and 93% O2.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1503286 TI - [Effect of hygrophobic filter or heated humidifier on peroperative hypothermia]. AB - A study was carried out to find out whether the use of a hygrophobic filter (Pall, Ultipor) or of a heated humidifier (Drager, Aquapor) during surgery had any effect on a patient's intraoperative core temperature and thermal balance. Seventy-five ASA I or II patients scheduled for gynaecological surgery were randomly assigned to three groups: group A (n = 25), where no warming device was used; and two groups (n = 25 for each) where inhaled gases were humidified and heated with either a hygrophobic filter set up between the endotracheal tube and the Y-piece (group B) or a heated humidifier set to 100% saturation at a temperature of 41.5 degrees C (group C). The patients were all anaesthetised with the same technique (thiopentone 5 mg.kg-1, dextromoramide 0.03 mg.kg-1 and 0.1 mg.kg-1 of either pancuronium or vecuronium, followed by enflurane with nitrous oxide in oxygen); the perfused fluids were not heated. Room, tympanic, rectal, oesophageal and four skin (thorax, arm, leg, thigh) temperatures were measured with calibrated Exacon thermistances, on arrival in the operating theatre, during induction, every ten minutes for two hours, and then every twenty minutes for two hours more. Ramanathan's and Burton's formulae were used to calculate mean skin temperature and heat loss respectively. In the recovery room, patients were warmed up with an electric blanket. Shivering was ranked from "0" to "+ +". There were no differences between groups as far as age, drug doses, perfusion volumes and room temperature were concerned.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1503287 TI - [Antibioprophylaxis in pulmonary surgery: a randomized trial with cefamandole versus placebo]. AB - A prospective double-blind study was designed to assess the efficacy of antibiotic prophylaxis in lung surgery. It included 114 patients undergoing lung surgery for primary or secondary malignant tumours randomly assigned to two groups. Group A patients (n = 59) were given cefamandole intravenously every four hours, three times, starting from induction of anaesthesia. The dose was determined according to the patient's weight: 1.5 g for patients weighing less than 60 kg, 2.5 g for those weighing between 60 and 80 kg, and 3 g for those above 80 kg. Group B patients (n = 55) were given a placebo at the same times. Nineteen other patients were excluded because either the tumour was found to be infected, or the patient had to be mechanically ventilated postoperatively, or an exploratory thoracotomy only was carried out, or they were allergic to beta lactam antibiotics. The efficacy of antibiotic prophylaxis was assessed by recording the incidence of postoperative infections, the length of the patient's stay in hospital, and the need to use an antibiotic treatment. Patients, their sputum and wound were examined every day, and their temperature recorded. The white blood cell count and chest X-ray was carried out every day for the first week. All the drain and catheter tips were cultured, as well as sputum and blood (every three days). In case of infection, samples were obtained and cultured. Both groups of patients were similar with regard to age, risk factors (smoking habit, diabetes mellitus), and type of surgery (segmentectomy, lobectomy, pneumonectomy). There were 9 postoperative infections in group A, and 22 in group B (p = 0.003).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1503288 TI - [Thrombosis of the superior vena cava after prolonged catheterization. Treatment by progressive removal of the catheter combined with urokinase-heparin administration]. AB - A retrospective study of 13 cases of complete superior vena cava thrombosis due to prolonged catheterization is reported. All the polyurethane catheters had been inserted by anaesthetists in theatre between January 1985 and December 1989, using Seldinger's technique. On the 10th day after the first catheter had been placed, the catheter was replaced by using a guide wire. Superior vena cava obstruction was diagnosed clinically (eyelid, neck, facial and upper limb oedema, cyanosis, collateral venous circulation, lack of blood reflux in the catheter). The clinical diagnosis was confirmed by phlebography. Treatment consisted in administration of urokinase (1,500 IU.kg-1.h-1), together with 10,000 to 25,000 IU.day-1 of heparin, both being injected via the catheter. The catheter was removed progressively (1 cm every 2 to 4 h). As soon as a venous pressure curve was obtained, the catheter was completely removed. Overall 8,784 catheters were inserted during that period. The incidence of superior vena caval obstruction may therefore be estimated to be 1.48 per 1,000 catheters. The catheters remained in place up to a mean of 14.75 +/- 9.6 days before the obstruction occurred. Treatment with urokinase and heparin lasted a mean of 2.53 +/- 1 days. The clinical picture returned to normal in all 13 patients. Phlebography carried out in three of them, after treatment, showed an excellent degree of venous repermeability. Thrombolysis was confirmed by the increase in the concentration of D-dimers, without any decrease in fibrinogen concentration. There were five haemorrhagic complications, including two haematomas of the psoas muscle, one of which required surgical drainage.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1503289 TI - [Effects of diazepam and incidence of hypoxemia during acute chloroquine poisoning]. AB - The effects of diazepam and the incidence of hypoxaemia on the course of acute chloroquine poisoning were studied prospectively in 21 patients. Were excluded patients who had ingested more than one drug or who had major symptoms on admission (systolic blood pressure less than 80 mmHg; QRS greater than 0.12 s; cardiac dysrhythmias, respiratory disturbances). Arterial blood gases were measured on admission (T0) and 15 min after 0.5 mg.kg-1 of diazepam had been given (T1). Gastric lavage was carried out as soon as the results of the blood gases had been obtained, and after treatment of hypoxaemia (PaO2 less than 90 mmHg). An infusion of diazepam (1 mg.kg-1.day-1) was then given. Arterial blood gases were measured after 1 (T2), 6 (T3), 12 (T4) and 24 h (T5). Hypoxaemia was present on admission in four patients who had a PaO2 = 75 +/- 10 mmHg (Pa(sys) = 130 +/- 19 mmHg; blood chloroquine concentration = 8.2 +/- 5.2 mumol.l-1; kaliemia = 3.1 +/- 0.3 mmol.l-1; PaCO2 = 35 +/- 1 mmHg). In two patients, hypoxaemia decreased after the initial dose of diazepam (T1); however, oxygen was still required by the other two at that time. Oxygen was no longer needed by any patient at T2, as all the blood gas values had returned to normal.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1503290 TI - [Effects of diazepam on mortality from acute chloroquine poisoning]. AB - A retrospective study was carried out, over a twelve-year period, of all cases of acute chloroquine poisoning where more than 2 g of chloroquine had been taken. It included 386 patients; of these, 60 who had taken drugs other than chloroquine, and 17 who had ingested less than 1 g of the drug, were excluded. The remaining 309 patients were allocated to two groups: a "control group", consisting of the patients admitted between January 1973 and April 1980 (n = 146), and a "diazepam group", made up of those admitted from May 1980 to December 1989 (n = 163). The patients in the latter group had had the same symptomatic treatment as those in the control group, and had been routinely given a 0.5 mg.kg-1 bolus of diazepam on admission followed by 0.1 mg.kg-1.day-1 for every 100 mg of chloroquine supposed to have been ingested. Both groups were divided into three subgroups, those patients with cardiorespiratory arrest, and those with, and those without, symptoms on admission. No statistically significant difference was found between either the control and diazepam groups or between subgroups, concerning the distribution of age, sex, amount of chloroquine supposed to have been ingested, delay in hospital admission and death rate. However, there was a higher death rate in the asymptomatic subgroup not treated with diazepam than in the diazepam group. Therefore, the routine use of diazepam for the treatment of acute chloroquine poisoning does not seem to be justified in symptomatic cases and in those with inaugural cardiac arrest.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1503291 TI - [Prostate transurethral resection syndrome]. AB - The "transurethral resection of prostate" syndrome (TURPS) is the clinical manifestation of the resorption into the patient's body of a large amount of glycocolle-containing irrigating fluid used for this procedure. The full clinical picture, which is seldom seen, consists of dyspnoea, nausea, arterial hypertension, an increased central venous pressure, cerebral oedema, cardiogenic shock and renal failure. Improved surgical techniques, as well as incomplete and atypical forms of the syndrome could explain this low incidence. Absorption into the blood stream may be rapid, by way of the prostatic venous plexi, or slower, from the spaces around the prostate and under the peritoneum. The present-day pathophysiological theory explains this syndrome by an acute hyponatraemia, sometimes dissociated from the hypoosmolality, the toxicity of glycocolle, and the neurological effects of hyperammonemia. Acute hyponatraemia, with blood sodium concentrations below 115 to 120 mmol.l-1, should be considered as potentially serious. The different mechanisms involved may act alone or together, thus explaining that the minor forms of the syndrome mostly consist of a neurological picture. The emergency treatment depends on the natraemia. It includes diuretics and progressive reloading of the patient with sodium in case of severe hyponatraemia with seizures. The best prevention is a correct surgical indication and technique. The resection should not last for more than 90 to 120 min. The major problem remains the early diagnosis of TURPS. Carrying out this surgery under regional anaesthesia is helpful for this purpose, but, in the near future, the best means might be the monitoring of expired ethanol concentrations. PMID- 1503292 TI - Clinical separation of the lungs. PMID- 1503293 TI - [Evaluation of 5 years of experimental in utero surgery for the repair of diaphragmatic hernia]. AB - The incidence of diaphragmatic hernia in he newborn is 1:2,500 to 5,000 births. An extensive American programme of foetal surgery for in utero repair of this defect has shown that the pulmonary hypoplasia was due to compression of lung tissue by the herniated organs. This process could be interrupted be repairing the diaphragmatic defect early enough in utero (before the 28th week). The results of five years of experimental surgery for in utero correction of diaphragmatic hernia are presented here. The experimental model used was the Macaca fascicularis monkey, the pregnant female of which having several gestational and endocrine characteristics similar to those of the pregnant woman. Three different experimental programmes were carried out successively. A first series including five animals was used to experiment both surgical and anaesthetic techniques; three foetuses died in utero. The second series (10 animals) was designed to find a suitable protocol for tocolysis. One female died after surgery, and seven other foetuses also died. The third group (13 animals) was the main study group. The diaphragmatic hernia was first created surgically, and then repaired. No foetus died from the surgery. One female died before giving birth, and one offspring died shortly after birth as its mother had no milk. After the encouraging results obtained with this last series of animals, the procedure was applied to human cases, with the Hospital Ethical Committee's approval. In the first case, the foetus died postoperatively as a result of the rupture of the diaphragmatic prosthesis.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1503294 TI - [Cardiac tamponade and central venous catheterization]. AB - A 32-year-old female patient was operated on for a residual colonic stricture occurring after hemicolectomy. A right internal jugular central venous catheter was inserted during the anaesthetic for postoperative parenteral feeding. The anaesthetic combined both general and epidural anaesthesia, the latter being continued for postoperative analgesia (10 ml.h-1 of 0.125% bupivacaine). Two days later, the patient complained of sudden chest pain, with restlessness, tachycardia, cyanosis, resulting in ventricular tachycardia and cardiac arrest. When admitted to the surgical intensive care unit, the patient was in deep coma and had nonsustained ventricular tachycardia, a left haemopneumothorax and a pneumopericardium. The patient died before a definitive diagnosis was made. Postmortem examination revealed an ulcerated anterior pillar of the tricuspid valve, as well as a perforation of the right ventricle and a communication between the pericardium and the left pleural cavity. The diagnosis and treatment of this rare life-threatening complication may be very difficult. It prevention consists in using short catheters for internal jugular venous access, and checking the tip's position radiologically by opacifying the catheter. PMID- 1503295 TI - [Acute respiratory insufficiency caused by diffuse pulmonary hemorrhage]. AB - Two cases of adult respiratory distress syndrome due to diffuse pulmonary haemorrhage are reported. The first patient was treated with azathioprine, prednisolone, cyclosporine and ranitidine for haemorrhagic rectocolitis; the second has untreated primary biliary cirrhosis. Haemoptysis only occurred in the latter. Both had severe isolated hypoxaemia. Chest X-rays revealed bilateral alveolar infiltrates. Bronchoscopies showed a diffusely bleeding bronchial tree. Both patients recovered after having been mechanically ventilated with positive end-expiratory pressure for six and eight days respectively. The cause of the diffuse pulmonary haemorrhage was, in the first case, severe thrombocytopaenia (17,000 G.1-1) of central origin, and, in the other patient, an unspecified vasculitis. Diffuse pulmonary haemorrhage should be added to the list of possible causes of the adult respiratory distress syndrome. PMID- 1503296 TI - [Acute respiratory insufficiency in sickle cell disease]. AB - Two cases are reported of acute respiratory failure occurring during sickling crises. In the first one, the crisis was characterised by priapism, and in the other one, by abdominal pain. The different causes of these respiratory effects are discussed: infection, fat embolism, pulmonary infarct, haemodynamic pulmonary oedema, as was probably the case in the first patient, or non haemodynamic pulmonary oedema due to sickling, as during conventional treatment of a sickling crisis (oxygen, antibiotics, blood transfusion, cytapheresis). Invasive investigations may contribute to keeping up the clinical picture, because of hypoxic sickling. The water equilibrium of these patients must be monitored with great care. Worsening of the patient's condition despite 48 h of correct treatment must lead to the search for a specific cause. PMID- 1503297 TI - [Treatment of algodystrophy of the knee: diagnostic error and misplacement of the peridural catheter]. AB - A fifty-year-old female patient, with a history of reflex sympathetic dystrophy of the left hand and right ankle, complained of pain in her right knee. The skin was slightly oedematous and red, whereas the knee X-ray was quite normal. These findings were thought to be related to another episode of reflex sympathetic dystrophy, and treatment with continuous epidural morphine and lidocaine was prescribed. Catheter insertion was uneventful. However, the lack of pain relief led to the suspicion of femoral neuralgia. Plain X-ray films of the lumbar spine showed the epidural catheter to be passing through the L2-3 foramen. The catheter was removed. The development of fever and major inflammatory signs of the knee revealed gout arthritis. This case stresses the need for careful repeated clinical examination in order to make the right diagnosis. On the other hand, when the expected effect of drugs administered by the epidural route fails to appear, the catheter's position should be promptly checked by X-ray. PMID- 1503298 TI - [Paraplegia after spinal anesthesia]. AB - A case of paraplegia occurring after a spinal anaesthetic is reported. The 79 year-old man was admitted for a fractured neck of femur. Twenty years previously, he had had pharyngeal surgery and a tracheostomy. He had also undergone a prostatectomy for prostate cancer, and had been on oestrogen therapy for two years. He complained of dyspnoea at rest and his chest film showed diffuse pulmonary opacities. In order to avoid possible intubation and respiratory complications, spinal anaesthesia was performed without any problems in the L4 space. After the surgery, the patient recovered all his motor and sensory functions in the lower limbs. On the second postoperative day, he suffered from a motor paralysis of the right leg, which spread to the left leg on the fourth day. NMR imaging showed several vertebral metastases, together with anterior and lateral epidural invasion responsible for cord compression. Treatment with tetracosactide was begun, but the patient died six weeks later in his home, not having recovered any neurological function at all in his lower limbs. In fact, it was only after the procedure that the anaesthetist was informed that, at the time the prostate cancer had been diagnosed, vertebral body metastases, of which the patient had not been informed, were already present. The part played by the spinal anaesthetic in the occurrence of the paraplegia is not clear. It is reminded that such a technique should be used with extreme care in patients having a neoplasm with a very often high incidence of vertebral metastases. PMID- 1503299 TI - [Pharmacology of nalbuphine]. PMID- 1503300 TI - [Fetal surgery: a new challenge for the 1990's]. PMID- 1503301 TI - [What is the value of preoperative determination of blood potassium levels?]. PMID- 1503302 TI - [Apropos of patient's refusal for blood transfusion]. PMID- 1503303 TI - [Anesthesiologists and Jehovah's witnesses]. PMID- 1503304 TI - [Late acute respiratory insufficiency after buprenorphine injection]. PMID- 1503305 TI - [Antitoxin accident during botulism]. PMID- 1503306 TI - [Incidence of thromboembolism depending on the type of surgery]. PMID- 1503307 TI - [Benefits and risks of hemodilution alone or associated with other techniques in the prophylaxis of thromboembolism]. PMID- 1503308 TI - [Prevention of thromboembolism by elastic compression]. PMID- 1503309 TI - [Prevention of thromboembolism by intermittent external pneumatic compression]. PMID- 1503310 TI - [Benefits and risks of unfractionated heparin in orthopedic surgery]. PMID- 1503311 TI - [Benefits and risks of unfractionated heparin in general surgery]. PMID- 1503312 TI - [Prevention of venous thrombosis with antiplatelet agents]. PMID- 1503313 TI - [Benefits and risks of antithrombin III concentrates]. PMID- 1503314 TI - [What are the costs of various preventive methods ?]. PMID- 1503315 TI - [Physical modeling of inhalation anesthesia]. AB - A new physical model simulating the pharmacokinetics of volatile anaesthetics is presented. It consists in a ventilator connected to a water manometer. Gas is removed from the gaseous part of this manometer with a constant rate pump. This gas flow is directed thereafter into three capacitances with valves and pumps: one capacitance only contains air, representing the lungs, and the other two olive oil, representing the visceral and muscle compartments. Halothane, enflurane and isoflurane (1 vol%) were administered to this model with different values of cardiac output and alveolar ventilation. There was good concordance between the values of FA/FI that were measured in this model and those calculated by computer simulation. No correction factor was required. Such a physical model may therefore be used to test new techniques of administration of volatile agents. PMID- 1503316 TI - [Venous echo Doppler: a future standard test in the diagnosis of thrombosis of the lower limbs?]. AB - Duplex ultrasound imaging provides both an ultrasound picture of the tissue being explored and the sound of the flow speed in a particular area. Colour Doppler imaging gives colour codes for the different flow rates. Venous pathology is always investigated, with ultrasound, on both sides, at the iliac and caval, femoral, and foreleg levels. For the latter, excellent equipment and patient position are required. Ultrasound criteria of deep venous thrombosis (DVT) are the incompressibility of the vein being investigated, and detection of the thrombosis with the ultrasound probe. Doppler criteria are asymmetric spontaneous flows, the loss of their respiratory rhythm, and the lack of flow induced by contraction of muscle. The colour Doppler draws provides the contours of a partial or floating thrombus. Compared with phlebography, ultrasound imaging has a sensitivity and specificity of 96%. Colour Doppler imaging is even more accurate: both sensitivity and specificity increase to 100%. The limitations of ultrasound are: its dependence on the investigator, the difficulty of making the diagnosis of recurring DVT when there already are previous sequellae, obesity, intra-abdominal gas, skin lesions or inflammatory oedema. Phlebography remains necessary in 5% of cases. The advantages of this technique are its non invasiveness, excellent diagnostic performance, low cost, and the possibility of diagnosing another cause, whether responsible for the clinical signs or not. It is indicated for the diagnosis of DVT, routine screening in patients at risk, and the early and late follow-up of patients. Today, ultrasound imaging should always be carried out before other investigations.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1503317 TI - [Accidental spinal anesthesia in obstetrics. Limits of epidural test-dose]. AB - Two cases of accidental spinal anaesthesia occurring in obstetrical patients are reported and discussed. Epidural anaesthesia had been asked for by the women, both being free from any significant medical history. A Tuohy needle was inserted in the midline between L3 and L4 with the patient sitting. The extradural space was identified by the loss of resistance using saline. The test-dose (2 ml and 4 ml of 1% lignocaine respectively) was administered five minutes before changing the patient to the supine position. In the first case, after a test-dose had remained without any effect, 8 ml of 0.25% bupivacaine were injected, about one hour later. The patient rapidly complained of paralysis of her legs and difficulties in breathing. Her blood pressure decreased from 120/80 mmHg to 90/60 mmHg. The upper level of analgesia reached T4. She improved after infusion of 1.51 of lactated Ringer's solution. Endotracheal intubation was not required. Delivery was assisted with a vacuum extractor. In the other patient, when the extradural space had been located, there was a small reflux of clear fluid which did not contain any glucose. As the test-dose did not result in any effect. 2 ml of 2% lignocaine with adrenaline were injected. This was followed by an immediate sensory loss in the legs, extending up to T10. Caesarean section was decided on, without any further injections (foetal macrosomia, breech presentation). Both patients totally recovered without any sequela. Both children had an Apgar score of 10 at 1 and 5 minutes. The type of test-dose is discussed. Smaller volumes of more concentrated solutions are recommended. PMID- 1503318 TI - [Abscess of the atrium: a complication of central venous catheters]. AB - A 27-year-old female patient was admitted for parenteral feeding and treatment of an acute episode of her steroid dependent Crohn's disease. An intravenous catheter was inserted, the tip being located in the right atrium. This central line was accidentally removed ten days later and replaced with another one also ending in the right atrium. The patient's condition improved over a four-week period. Thereafter, she suddenly became confused and complained of abdominal pain with contracture. She displayed renal failure, coagulation disorders, and decreased blood cell counts. This was followed by a septic shock requiring mechanical ventilation and adrenaline. Laparotomy failed to reveal a cause for the patient's condition. She improved and was extubated four days later. From then on, she had fever (39 degrees C) again. Her catheter was replaced, the tip of this third one being inside the superior vena cava. Staphylococcus epidermidis was obtained from the catheter tip, as well as from four consecutive blood cultures. Despite administration of three different antibiotics, the high fever persisted (40 degrees C). Finally, the occurrence of a systolic murmur led to the discovery, with cardiac ultrasonography, of a mobile right atrial abscess, which engaged into the tricuspid valve at every contraction. Surgery to remove this mass was rapidly carried out. The bacterium was the same as that which had been isolated from the catheter. The patient improved and was able to return home a fortnight later. The diagnosis and prevention of this complication is discussed. The tip of central venous catheter should not be kept inside the atrium. PMID- 1503319 TI - [Clinical study of EMLA analgesic cream in pediatric locoregional anesthesia]. AB - The advantage of EMLA cream for regional blocks (spinal or caudal blocks) was assessed in 46 children. The study included three groups: group 1, with 1 to 6 month-old children (n = 11); group 2, with children aged between 6 months and 5 years (n = 21), scheduled for emergency surgery and with full stomach; group 3, with 5 to 10 year-old children (n = 14), who were to have a regional block as an alternative to general anaesthesia. The cream was applied as a thick layer on the area of skin to be anaesthetised and covered by a closed adhesive dressing, approximately 2.2 h before performing the regional block. A dose of 1 to 2 g was used in children of more than 1 year, and 0.5 to 1 g for those of less than 1 year. All the blocks were carried out by the same anaesthetist. The technique was considered as being little (45/46) or not constraining (1/46). Patient cooperation in carrying out the regional block was judged to be good or very good in 34/46 children. Additional sedation was required in 7 children of groups 2 and 3. The block was as easy to carry out as usual in 37/46 children. In all three groups, most children complained of little or no pain. Local adverse effects occurred in 19/46 patients, consisting of erythema (14), skin paleness (4), or both (1). The investigator qualified the use of EMLA cream as satisfactory or very satisfactory in 36/46. It is concluded that EMLA cream provides convenient analgesia for regional blocks in toddlers and children. PMID- 1503320 TI - [Tracheal intubation in patients with cervical spine injuries using a fiber optic laryngoscope]. AB - Eleven patients, with a cervical spine injury and scheduled for elective cervical spine fusion at least 48 h after their initial trauma, were intubated using a new fiberoptic laryngoscope (Bullard). This technique uses either a semi-rigid guide independent of the laryngoscope blade, or a rigid one attached to the blade. The cervical spine was immobilized with either a collar or a halo. General anaesthesia was carried out with thiopentone, fentanyl and vecuronium bromide. Orotracheal intubation was successful at the first attempts in 10 out of the 11 patients. No mobilization of the cervical spine occurred. In the first six patients, the semi-rigid guide was used, and the rigid one in the remaining five. The anaesthetist who carried out the intubations was always the same. Using the rigid guide was easier than the semi-rigid one. This is confirmed by the time required, 44 +/- 22 sec for the rigid guide, and 97 +/- 92 sec for the semi-rigid one. In the patient in whom this technique failed at the first attempt, endotracheal intubation was carried out by the nasal route and controlled by the fiberoptic laryngoscope. This technique enables a rapid and easy orotracheal intubation in trauma patients with an immobilized cervical spine, but careful training is necessary. PMID- 1503321 TI - [Diphosphonates: read the instructions]. PMID- 1503322 TI - [Absence of mast cell degranulation during general anesthesia in a child with mastocytosis]. PMID- 1503323 TI - [Laryngeal mask in pediatrics]. PMID- 1503324 TI - [Combination of propofol and alfentanil for corneal surgery in a patient with Duchenne de Boulogne disease]. PMID- 1503325 TI - [A simplified model for anesthesia with a reinhalation circuit]. PMID- 1503326 TI - A low-molecular-weight heparinoid compared with unfractionated heparin in the prevention of deep vein thrombosis in patients with acute ischemic stroke. A randomized, double-blind study. AB - OBJECTIVE: To compare the relative safety and efficacy of a low-molecular-weight heparinoid (ORG 10172) with unfractionated heparin in the prevention of deep vein thrombosis in patients with acute ischemic stroke. DESIGN: Double-blind randomized trial. SETTING: Seven Canadian university-affiliated hospitals. PARTICIPANTS: Eighty-seven patients with acute ischemic stroke resulting in lower limb paresis. INTERVENTION: Patients received either low-molecular-weight heparinoid, 750 anti-factor Xa units twice daily, or unfractionated heparin, 5000 units subcutaneously twice daily. Treatment was continued for 14 days or until hospital discharge if sooner. MEASUREMENTS: Deep vein thrombosis was diagnosed using 125I-labeled fibrinogen leg scanning and impedance plethysmography. Venography was indicated if either test was positive. Overt hemorrhage, major or minor, was assessed clinically. RESULTS: Venous thrombosis occurred in four patients (9%) given low-molecular-weight heparinoid and in 13 patients (31%) given heparin (relative risk reduction, 71%; 95% CI, 16% to 93%. The corresponding rates for proximal vein thrombosis were 4% and 12%, respectively (relative risk reduction, 63%; P greater than 0.2). The incidence of hemorrhage was 2% in both groups. CONCLUSION: Low-molecular-weight heparinoid, given in a fixed dose of 750 anti-factor Xa units subcutaneously twice daily, is more effective than subcutaneous low-dose heparin for the prevention of deep vein thrombosis in patients with acute ischemic stroke. PMID- 1503327 TI - Fibrinogen and viscosity as risk factors for subsequent cardiovascular events in stroke survivors. AB - OBJECTIVE: To investigate whether abnormalities in blood viscosity predict a poor prognosis for subsequent cardiovascular events in stroke survivors. DESIGN: Nested case-control study among a cohort of survivors of a first stroke, followed for an average of 2 years. Patients with a second stroke, myocardial infarction, or cardiovascular death were matched with patients who did not have such events (control patients). SETTING: Buchberg-Klinik, Bad Tolz, Germany, a specialized center for stroke rehabilitation. PATIENTS: A total of 625 consecutive patients. Twenty-one patients (3.5%) were lost to follow-up. Sixty pairs were matched. MEASUREMENTS: Native and hematocrit-standardized blood viscosity at three shear rates, hematocrit, plasma viscosity, fibrinogen, erythrocyte sedimentation rate, total leukocyte count, and the matching variables. RESULTS: Eighty-five patients had a second stroke, myocardial infarction, or died due to a cardiovascular event. Patients with re-events had higher blood viscosity and fibrinogen levels than the control patients. In the 60 matched pairs, the mean of the paired differences between patients with re-events and control patients was 5.03 mPa.s (95% CI, 1.262 to 8.941; P = 0.01) for native blood viscosity at shear rate 0.7 s 1, for plasma viscosity, 0.044 mPa.s (CI, 0.006 to 0.083; P greater than 0.02), and for fibrinogen, 0.056 g/L (CI, 0.010 to 0.101; P greater than 0.02). Odds ratios were significantly increased only for plasma viscosity (odds ratio, 2.86; CI, 1.06 to 8.43) and fibrinogen (odds ratio, 3.67; CI, 1.31 to 11.69). CONCLUSIONS: Hyperfibrinogenemia is an independent risk factor for cardiovascular events in stroke survivors. Intervention trials with fibrinogen lowering measures may be warranted. PMID- 1503328 TI - Comparison of the specificity and sensitivity of Hemoccult and HemoQuant in screening for colorectal neoplasia. AB - OBJECTIVE: To compare the Hemoccult II and HemoQuant tests regarding their specificity and sensitivity in screening for colorectal neoplasia. DESIGN: Cross sectional study in which subjects underwent the two tests in parallel, after excluding dietary hemes and peroxidase-rich foods. HemoQuant results were analyzed for three different upper limits of normality (1.5, 2.0, 3.0 mg/g feces). SETTING: A university hospital and the surrounding community. PARTICIPANTS: A total of 150 healthy volunteers, 124 patients with colorectal cancer, and 86 patients with adenoma. MAIN OUTCOME MEASURES: Blinded comparison of the specificity and the sensitivity of the two tests for colorectal cancer and adenoma. RESULTS: Test specificity was 99.3% with Hemoccult and was 92.7%, 94.7%, and 97.3% with HemoQuant, depending on the cutoff point; differences between Hemoccult and HemoQuant were significant when cutoffs of 1.5 and 2.0 mg/g were used in HemoQuant testing (6.6% [95% CI, 2.3 to 11.1] and 4.7% [CI, 0.8 to 8.5], respectively). Test sensitivity for colorectal cancer at all sites was 89.5% with Hemoccult and was 83.1%, 74.2% and 62.9% with HemoQuant, for the 1.5, 2.0, and 3.0 mg/g cutoffs, respectively; differences were significant with the 2.0 and 3.0 mg/g cutoff points (6.4% [CI, 6.7 to 24.0] and 26.6% [CI, 17.4 to 35.9%], respectively). The two tests had similar levels of sensitivity for cancers proximal to the splenic flexure, but sensitivity was substantially lower with HemoQuant for the more distal cancers. For all adenomas, test sensitivity was 30.2% with Hemoccult and ranged from 45.4% to 22.1% with HemoQuant. CONCLUSIONS: Although HemoQuant provides a precise measurement of fecal heme and its porphyrin degradation products, the test's performance characteristics in the detection of colorectal neoplasia are less satisfactory than those of Hemoccult II, a qualitative test for the presence of heme. PMID- 1503329 TI - Return to work after uncomplicated myocardial infarction: a trial of practice guidelines in the community. AB - OBJECTIVE: To evaluate the effectiveness of practice guidelines for return to work after acute myocardial infarction when disseminated from a university-based setting to a practice-based setting. DESIGN: Randomized clinical trial. PATIENTS: A total of 187 patients with uncomplicated acute myocardial infarction. INTERVENTION: Patients were randomly assigned to the intervention (n = 95) or to usual care (n = 92). The intervention consisted of a treadmill test, a counseling session based on the test results, and a consultation letter from a cardiologist to the primary care physician. Individualized recommendations for the timing of return to work, contained in the consultation letter, were based on the patient's risk for recurrent cardiac events. MEASUREMENTS: Questionnaire, chart review, and a phone interview documented the timing of return to work and the rates of cardiac death, coronary angioplasty, coronary artery surgery, and recurrent myocardial infarction. RESULTS: Median intervals between acute myocardial infarction and return to work were similar in both groups (intervention, 54 days; usual care, 67 days; P greater than 0.2). Among patients without myocardial ischemia, however, the interval was shorter in the intervention group than in the usual care group (38 days compared with 65 days, respectively, P = 0.008). Among patients with myocardial ischemia, intervals were similar in both groups (80 days compared with 76 days, respectively, P greater than 0.2). CONCLUSION: Practice guidelines developed in a university-based setting were not as successful in hastening return to work after uncomplicated acute myocardial infarction when tested in a practice-based setting. Physicians' reluctance to follow guidelines for patients with myocardial ischemia reflected their concern with prognosis even though medical outcome was good. PMID- 1503330 TI - Trimethoprim-sulfamethoxazole compared with vancomycin for the treatment of Staphylococcus aureus infection. AB - OBJECTIVE: To compare trimethoprim-sulfamethoxazole (TMP-SMZ) and vancomycin regarding efficacy and safety in the therapy of serious Staphylococcus aureus infections. DESIGN: Randomized, double-blind comparative trial. SETTING: A tertiary-care hospital. PATIENTS: One hundred and one intravenous drug users hospitalized with S. aureus infection. MEASUREMENTS: Cure and failure rates; blood and wound cultures; minimum inhibitory and bactericidal concentrations; serum inhibitory and bactericidal titers; temperature; leukocyte count; durations of treatment and hospitalization; and toxicity. RESULTS: Of 228 intravenous drug users, 101 had S. aureus infection and were included in the efficacy analysis (43 received TMP-SMZ and 58 received vancomycin). Methicillin-resistant S. aureus (MRSA) accounted for 47% of S. aureus isolates, and 65% of patients were bacteremic. Infections were cured in 57 of 58 vancomycin recipients and in 37 of 43 TMP-SMZ recipients (P less than 0.02). Failure occurred mostly in patients with tricuspid valve endocarditis and only in those with infection caused by methicillin-sensitive S. aureus (MSSA). The mean duration of bacteremia was 6.7 days in TMP-SMZ recipients and 4.3 days in vancomycin recipients. Among 222 subjects hospitalized for at least 24 hours, toxicity rates were similar for TMP SMZ (23%) and vancomycin (20%) recipients; nausea and vomiting were associated with TMP-SMZ and inflammation at the intravenous site was associated with vancomycin. Forty-four percent of TMP-SMZ recipients and 29% of vancomycin recipients experienced side effects in the efficacy cohort (P greater than 0.05). CONCLUSIONS: Vancomycin is superior to TMP-SMZ in efficacy and safety when treating intravenous drug users who have staphylococcal infections. However, all treatment failures occurred in patients with MSSA infection at any site. Therefore, TMP-SMZ may be considered as an alternative to vancomycin in selected cases of MRSA infection. PMID- 1503331 TI - Sarcoidosis with multiple hepatic and splenic nodules on dynamic computed tomography. PMID- 1503332 TI - Cholangiopathy associated with Microsporidia infection of the common bile duct mucosa in a patient with HIV infection. PMID- 1503333 TI - Autocrine secretion--10 years later. AB - The concept of autocrine secretion, its subsequent modifications, its application for understanding pathogenesis of disease, and its potential for developing new approaches to prevention and treatment are reviewed. Peptide growth factors (cytokines) act as local autocrine and paracrine mediators of tissue homeostasis. Many diseases, including cancer, atherosclerosis, rheumatoid arthritis, and other fibrotic diseases characterized by chronic inflammation, are associated with aberrant expression and cellular coordination of the homeostatic action of these regulatory molecules. Modern biotechnology and pharmacology offer unique opportunities for the therapeutic prevention and treatment of these molecular and cellular lesions, using either cytokines or other agents that modify their synthesis and activity. PMID- 1503335 TI - Examined at forty. PMID- 1503334 TI - NIH conference. Respiratory disease in the immunosuppressed patient. AB - Pulmonary complications, both infectious and noninfectious, are an important cause of morbidity in patients with various types of immunosuppression. The appropriate response to these clinical problems requires an understanding of pulmonary host defense and of the various types of systemic immunosuppression. Infectious and noninfectious pulmonary complications may vary according to the type of immunosuppression as well as to the degree and duration of immunosuppression. Appropriate clinical management also requires an understanding of the clinical problems commonly seen in specific groups of immunosuppressed patients and an understanding of the sensitivity, specificity, and potential complications associated with the available diagnostic approaches to those patients. Because respiratory disease in these patient groups may progress rapidly to respiratory failure, an expeditious evaluation based on the knowledge of likely causes of respiratory disease and prompt specific or empiric therapy are indicated. Specific sets of algorithms for the evaluation of both focal and diffuse pulmonary disease may facilitate such an evaluation. In addition, an aggressive approach to the prevention of pulmonary disease including immunization, prophylaxis, and immunomodulation (for example, colony stimulating factors) may be warranted in specific subgroups at risk. PMID- 1503336 TI - New directions in the immunology of autoimmune diabetes. PMID- 1503338 TI - Strategies for elective red blood cell transfusion. PMID- 1503337 TI - Strategies for elective red blood cell transfusion. PMID- 1503339 TI - Strategies for elective red blood cell transfusion. PMID- 1503341 TI - Do restraints prevent falls? PMID- 1503340 TI - Do restraints prevent falls? PMID- 1503342 TI - TIPS-associated hemolysis and encephalopathy. PMID- 1503343 TI - Referred vagal reflexes. PMID- 1503345 TI - How immunoglobulins were named. PMID- 1503344 TI - Diabetic neuropathy and HLA-DR3/4. PMID- 1503346 TI - Levothyroxine binding by sucralfate. PMID- 1503347 TI - The influence of hyperglycemia on outcome of cerebral infarction. AB - OBJECTIVE: To determine whether hyperglycemia in the acute stroke period is associated with worse survival and functional outcome after accounting for acute stress response and chronic hyperglycemia. DESIGN: Prospective, county-wide, multicenter cohort study. SETTING: A community hospital, a university hospital, and a Veterans Affairs hospital. PATIENTS: A cohort of 146 patients hospitalized with new atherothrombotic stroke. MEASUREMENTS: Admission blood glucose concentration, demographic characteristics of patients, 24-hour urinary catecholamine, serum cortisol, and glycosylated hemoglobin levels; outcomes included mortality and functional outcome (Barthel index and Fugl-Meyer score) at 5, 30, 90, and 180 days after stroke. RESULTS: Of the 996 patients with possible acute stroke who were screened, 146 (15%) were eligible for and consented to participate in the study; in most cases, exclusion from study was based on the absence of acute, atherothrombotic stroke. Overall, no evidence was found of a significant univariate association between admission blood glucose level and survival (relative risk, 1.02; 95% Cl, 0.94 to 1.09) or functional outcome (univariate regression coefficient for adjusted Fugl-Meyer score at day 30, - 0.36; Cl, - 1.08 to 0.27). This absence of an association persisted after adjustment for significant predictors of outcome in a multivariate model. CONCLUSIONS: These data do not support an association between level of glycemia and outcome from acute stroke. PMID- 1503348 TI - In-vitro resistance to zidovudine and alpha-interferon in HIV-1 isolates from patients: correlations with treatment duration and response. AB - OBJECTIVE: To measure in-vitro antiviral drug susceptibilities of human immunodeficiency virus type 1 (HIV-1) isolates recovered from patients treated with alpha-interferon or zidovudine and patients not treated with these drugs and to examine the relation of these susceptibility measurements to duration of therapy, disease stage, and response to alpha-interferon therapy. DESIGN: Cross sectional study. SETTING: Outpatient HIV clinic. PATIENTS: Twenty-six ambulatory HIV-1-infected patients: Fifteen of these patients were receiving alpha interferon therapy, and 11 had never received such therapy. Nine patients were participating in a clinical trial of combination therapy with zidovudine and alpha-interferon. MEASUREMENTS: The 50% inhibitory concentration (IC50) of zidovudine and alpha-interferon was determined for HIV-1 isolates recovered from each patient. Plasma concentrations of HIV-1 p24 antigen in the nine patients in the clinical trial were measured monthly after alpha-interferon was added to zidovudine monotherapy. RESULTS: Zidovudine IC50 (range, 0.01 to 4.87 microM) increased steadily with duration of zidovudine therapy (r = 0.57, P = 0.003). In contrast, alpha-interferon IC50 (range, 0.8 to 415 units/mL) was not related to duration of alpha-interferon treatment; in fact, high IC50s were found in isolates from patients who had never received exogenous alpha-interferon therapy. Resistance to alpha-interferon was greater in isolates from the 15 patients with the acquired immunodeficiency syndrome (AIDS) (median, 104 units/mL) than in those from the 10 patients without AIDS (median, 50 units/mL). Interferson activity was detected in plasma samples from 23 of 24 patients and was also at higher levels in patients with AIDS than in HIV-infected patients without AIDS. Reductions in plasma concentrations of HIV-1 p24 antigen in nine patients after beginning alpha-interferon therapy were greater in those with more susceptible isolates (r = -0.72, P = 0.03). CONCLUSIONS: Interferon resistance, possibly due to endogenous interferon, is not related to duration of interferon therapy but may limit the effectiveness of interferon therapy. Determinations of interferon susceptibility may identify patients most likely to benefit from this agent. PMID- 1503349 TI - Patent foramen ovale as a risk factor for cryptogenic stroke. AB - OBJECTIVE: To determine and compare the prevalence of patent foramen ovale in patients with stroke of undetermined origin (cryptogenic) and in patients with stroke of determined origin to assess the possible role of patent foramen ovale as a risk factor for cryptogenic stroke. DESIGN: Cross-sectional study with nested case-control analysis. PATIENTS: A total of 146 patients (73 men, 73 women) with acute ischemic stroke referred to the echocardiography laboratory for evaluation. SETTING: Neurovascular Unit and Echocardiography Laboratory, Columbia Presbyterian Medical Center, New York, New York. MEASUREMENTS: Patients were considered to have strokes of determined origin or cryptogenic strokes according to National Institute of Neurological Disorders and Stroke (NINDS) Stroke Data Bank criteria. The presence of patent foramen ovale was assessed by contrast echocardiography, performed blinded for type of stroke. The association between patent foramen ovale and type of stroke was tested after correcting for patients' demographic variables and stroke risk factors. RESULTS: The overall prevalence of patent foramen ovale was 26 of 146 patients (18%; 95% Cl, 11.4% to 24.6%). Patients with cryptogenic stroke (31%) had a significantly higher prevalence of patent foramen ovale than did patients with an identifiable cause of stroke (69%) in both the younger (less than 55 years; 48% compared with 4%; P less than 0.001) and the older (greater than or equal to 55 years; 38% compared with 8%; P less than 0.001) age groups. Multiple logistic regression analysis was used to identify the presence of a patent foramen ovale as strongly associated with the diagnosis of cryptogenic stroke (odds ratio, 7.2; Cl, 2.4 to 21.7), irrespective of patient age and other stroke risk factors. CONCLUSIONS: Patients with cryptogenic stroke have a higher prevalence of patent foramen ovale than patients with stroke of determined cause in all age groups, even after correcting for the presence of recognized stroke risk factors. This identifies patent foramen ovale as a risk factor for cryptogenic stroke. Regardless of patient age, contrast echocardiography should be considered when the cause of stroke is unknown. PMID- 1503350 TI - Minocycline-induced cell-mediated hypersensitivity pneumonitis. AB - OBJECTIVE: To identify the cause of a hypersensitivity pneumonitis and to determine its pathogenesis. DESIGN: Case study. SETTING: Intensive care unit of a referral hospital. PATIENT: A 51-year-old man with chronic bronchitis who developed a hypersensitivity pneumonitis within 1 month after exposure to minocycline, amoxicillin, and erythromycin. INTERVENTION: Sequential bronchoalveolar lavages after reexposure to minocycline and amoxicillin. MEASUREMENTS: Immunologic analysis of the phenotype and function of alveolar lymphocytes. RESULTS: Reexposure to minocycline but not to amoxicillin was followed by an interstitial pneumonitis. Sequential bronchoalveolar lavages showed a transient rise of eosinophils and neutrophils and a persistent alveolar lymphocytosis. Alveolar lymphocytes consisted predominantly of CD8+ but also CD4+ cells. Two CD8+ lymphocyte subsets were identified: CD8+ D44+ cytotoxic T cells that increased rapidly after the drug was resumed and CD8+ CD57+ suppressor T cells that predominated 11 days after the drug's withdrawal. In-vitro assays showed the presence of a lymphocyte-mediated specific cytotoxicity against minocycline-bearing alveolar macrophages. CONCLUSION: These results support the hypothesis of a central role of T lymphocytes in the pathogenesis of drug-related hypersensitivity pneumonitis. PMID- 1503351 TI - Eosinophilic endomyocardial disease presenting as cyanosis, platypnea, and orthodeoxia. PMID- 1503352 TI - Zidovudine: five years later. AB - Zidovudine, a nucleoside analog, was the first agent proved to be effective in the management of human immunodeficiency virus type 1 (HIV-1) infection. After demonstration of zidovudine's in-vitro activity against HIV-1 in 1985, the drug was rapidly evaluated in phase I and phase II clinical trials and was found to be effective in decreasing both mortality and the incidence of opportunistic infections in patients with the acquired immunodeficiency syndrome (AIDS) and advanced AIDS-related complex; the drug was also found to have a substantial but tolerable toxicity profile. Since the licensure of zidovudine in 1987, an intensive clinical research effort has established the drug's efficacy in the prevention of disease progression in asymptomatic and mildly symptomatic HIV infected persons and has established the success of lower-dose therapy in patients at all stages of disease. The current recommendation is to use zidovudine at a dose of 500 to 600 mg/d in both symptomatic and asymptomatic persons with CD4 counts of less than 500/mm3. The major toxicities of anemia and neutropenia are less frequent at the lower doses presently used and can be managed by dose reduction or by use of hematopoietic growth factors. The inexorable disease progression seen despite zidovudine therapy and the isolation of clinical strains of HIV-1 resistant to zidovudine in vitro highlight the limitations of prolonged monotherapy with this agent. Although alternative dideoxynucleoside agents (for example, didanosine [dideoxyinosine and zalcitabine dideoxycytidine]) are available for the management of HIV-infected persons, zidovudine remains the cornerstone of antiretroviral therapy. Current research efforts are directed at elucidating the clinical relevance of zidovudine resistance and studying regimens in which zidovudine is used in combination with other agents. This latter approach holds great promise for improving efficacy, limiting toxicity, and perhaps preventing the emergence of viral resistance. For the forseeable future, zidovudine will continue to play a role in the development and in our understanding of antiretroviral therapy. PMID- 1503353 TI - Left ventricular diastolic dysfunction as a cause of congestive heart failure. Mechanisms and management. AB - OBJECTIVE: To define the mechanisms underlying left ventricular diastolic dysfunction in patients with congestive heart failure and normal systolic function and to identify the patients at risk for this syndrome. STUDY SELECTION: Studies were selected that describe the clinical observations of congestive heart failure with normal systolic function and that provide experimental and clinical insights into the mechanisms responsible for ventricular diastolic dysfunction. DATA SYNTHESIS: Recent studies indicate that a large number of patients (up to 40% in some series) presenting with congestive heart failure have preserved left ventricular systolic function. The factors contributing to altered left ventricular diastolic function include fibrosis, hypertrophy, ischemia, and increased afterload. The latter three factors, alone or in combination, predispose to impaired left ventricular relaxation, an active energy-requiring process. Thus, decreased left ventricular diastolic distensibility (increased diastolic pressure at any level of diastolic volume) may arise not only from altered passive elastic properties stemming from fibrosis or increased muscle mass but also from derangements in the dynamics of ventricular relaxation. RESULTS: In patients with essential hypertension, all four of the above mechanisms may be operative. Considering the prevalence of hypertension in the general population, hypertension appears to be an important underlying factor in many patients with heart failure on the basis of diastolic mechanisms. In the patient presenting with dyspnea and elevated filling pressures, but with a nondilated, normally contracting ventricle, treatment with standard heart failure medications (such as digitalis, diuretics, and vasodilators) is often ineffective and may be deleterious. Such patients may respond more favorably to beta-blockers and calcium-channel blockers. CONCLUSIONS: Diastolic dysfunction should be considered in the patient presenting with heart failure symptoms but with normal systolic function, particularly in hypertensive patients with left ventricular hypertrophy. PMID- 1503354 TI - Universal insurance for American health care. A proposal of the American College of Physicians. PMID- 1503355 TI - Cost effectiveness of cervical cancer screening for the elderly. AB - OBJECTIVE: To analyze the costs and benefits of alternative cervical cancer screening schedules among elderly women. SETTING: Population-based screening programs. DESIGN: A Markov model predicts the outcomes of periodic screening, diagnosis, and treatment for cervical cancer among women from 65 to 109 years of age. PATIENTS: A hypothetical cohort of one million 65-year-old women; representative of the U.S. population. MEASUREMENTS: The costs and yields of screening. RESULTS: Triennial screening reduced mortality from cervical cancer among the elderly by 74% at a cost of $2254 per year of life saved. Annual screening increased costs to $7345 per year of life saved; less frequent schedules yielded lower costs but decreased savings in life. These results were most sensitive to the quality of the Papanicolaou smear and the characteristics of the women using the benefit. If the sensitivity of the Papanicolaou smear was reduced from a baseline estimate of 75% to 50% and the specificity was decreased to 87% from 95%, the cost effectiveness ratio increased by nearly $7000 per year of life saved. If triennial screening is targeted to women who have not had regular screening, the program will save money as well as years of life; however, screening women who have been screened regularly is considerably less efficient, increasing costs to $33,572 per year of life saved. CONCLUSION: The success of the new Medicare benefit depends substantially on physicians assuring that their elderly patients, particularly women without regular prior screening, obtain high quality Papanicolaou smears. The data also show that after a woman 65 years of age or older has a history of regular negative smears, screening is inefficient and can cease. PMID- 1503356 TI - Health care reform: an American imperative. PMID- 1503357 TI - The cost effectiveness of cervical cancer screening. PMID- 1503358 TI - New macrolide antibiotics. PMID- 1503359 TI - New macrolide antibiotics. PMID- 1503360 TI - Paradoxic paradoxes. PMID- 1503361 TI - Fish oil supplementation and ulcerative colitis. PMID- 1503362 TI - Fish oil supplementation and ulcerative colitis. PMID- 1503363 TI - Overtreating hypertension. PMID- 1503364 TI - Arthritis after bacillus Calmette-Guerin therapy. PMID- 1503365 TI - Common prescribing errors. PMID- 1503366 TI - Inflammatory breast cancer. PMID- 1503367 TI - [Evaluation of the surgical risk in general surgery: usefulness of a predictive system based on statistical analysis]. AB - 1182 patients were prospectively studied in order to evaluate the surgical risk factors. Stepwise regression logistic procedure was employed for statistical analysis. Postoperative complications included death, cardiac, respiratory, hepatic and renal failure, wound infection and sepsis. Various preoperative conditions were associated with postoperative complications but some of them, as malnutrition or operations prolonged over two hours, occurred more frequently. Age did not appear as a major risk factor. The determination of surgical risk is a major problem in general surgical practice and many attempts have been realized in order to predict postoperative outcome. Clinical judgment is still nowadays fundamental but predictive scores based on statistical analysis have proved to be valid and useful tools. The authors underline the importance of surgical risk prediction in therapeutic programming, especially in the aged and in cancer patient. The surgical or non surgical option and the type of operation to be performed result from a careful evaluation of operative risk and expectancy and quality of life. PMID- 1503368 TI - [Evaluation of prognostic factors in general surgery; methodological aspects of a multicenter prospective study of 1182 patients]. AB - Surgical risk is defined as the probability of occurrence of early or late complications. For each patient, knowledge of factors affecting surgical risk in a basic step when evaluating prognosis after surgery and determining therapeutic decision. A greater and more effective information may be obtained studying variables within the context of the other ones that more or less condition them. Such a "multivariate" approach allows simultaneously investigating all characteristics by taking account of their correlations. Specification of the problem, choice of the relevant variables, data collection and statistical data processing were considered. Pros and cos of multiple logistic regression model in the assessment of surgical risk were reviewed. The index could be used to identify the most important factors in determining surgical risk and quantify their respective importance. In this way surgical patients could be classified according to risk level. This approach also allow for the concurrent investigation of various potential risk factors and their interactions. For this reason it is termed multifactorial. PMID- 1503369 TI - [Analysis of mortality and relative prognostic factors in general surgery: use of the multiple logistic regression model]. AB - Surgical risk is defined as the occurrence of complications arising in the individual as a result of surgical stress. The ability to forecast these consequences is an important factor in determining decision taken by surgeon. Several attempts have been made to quantify postsurgical prospects but up till now no overall solution has been found. This paper attempts to define a multifactorial risk index for adults subjected to surgery, with respect to immediate and early per- and post-surgical complications. 1182 adult patients, 14 yrs or more, surgically treated not for urgency during 1985 in six Italian centres, were prospectively studied in order to derive a multivariate prognostic index of after surgery mortality. Stepwise logistic regression model was applied to a set of preoperative and operative factors, five of which were found significantly correlate with death: nutritional status, renal failure, reintervention, bacterial contamination during surgery, age greater than 70 years. Thus, from regression coefficients, scores were derived for modalities of significant variables, allowing to build four classes of risk patients: low (less than 1%), medium (between 1% and 10%), high (between 10% and 50%), extremely high risk (greater than 50%). PMID- 1503370 TI - [Identification of the patient at risk of postoperative infectious complications: risk factors and their evaluation]. AB - The authors report their results of a prospective study on 1182 patients who underwent surgical operation relatively on postoperative infections. Studied variables were: structural and anamnestic: sex, age, smoking, drinking; clinical: evidence of functional changes in various organs, as assessed upon clinical basis and laboratory results; pertinent to surgical intervention: entity, duration, anaesthesia; during and early-after-surgery complications (until discharge or within 30 days since intervention). Stepwise logistic regression model was applied to this set of preoperative and operative factors, four of which were found significantly correlate with postoperative infections: bacterial contamination during surgery, duration surgical intervention greater than 120', cholestasis, serum albumin. PMID- 1503371 TI - [Mortality and clinico-prognostic significance of risk factors in geriatric surgery]. AB - A prospective study for assessment of operative risk in elderly patients was carried in 1182 adult patients, 14 yrs or more, surgically treated not for urgency during 1985 in six Italian centres. Looking for meaningful relations among prognostic factors and outcome of disease is a relevant topic in biomedical of surgical risk was the use of multiple logistic function. Anamnestic, clinical and surgical variables were "explicative" variables, while occurrence of death and postoperative complications were "response" variables. Multipathology (myocardiosclerosis, respiratory failure) frequently associated with advanced age (greater than 70 yrs) contribute to determine the prognosis in surgery of elderly patient. Stepwise logistic regression model was applied to a set of preoperative and operative factors, five of which were found to significantly correlate with death: nutritional status, renal failure, reintervention, bacterial contamination during surgery, age greater than 70 years. From our data some conclusion may be drown: it is emphasized the major role of surgical factors in affecting the postoperative risk; among clinical variables, renal failure furnishes the most relevant contribution to prognosis; advanced age itself does not substantially affect the surgical risk, its role being confounded by association with other pathologies. PMID- 1503372 TI - [Nutritional status and heart valve surgery: response to surgical aggression]. AB - Malnutrition is a condition of increased risk for surgical patients, yet incompletely understood. Its role in the prognosis of neoplastic, gastrointestinal and infective disease undergoing surgery is now better underlined; unfortunately the same attention is still lacking for the majority of cardiac diseases. Nowadays many methods are at hand for evaluation of nutritional status, and it is possible to restore the correct condition before surgery by various techniques of artificial nutrition. Here the authors consider the possibility of discovery and evaluation of various hidden conditions of malnutrition in patients suffering of valvular heart disease--depending or not from the cardiopathy itself--and their complex pathogenesis, to correct at the end such condition and offer the patients an optimal prognosis with therapeutical procedures. PMID- 1503373 TI - [Head trauma in a general surgery department: observations, diagnostic and therapeutic indications]. AB - The authors reviewed the records of 927 patients admitted to Surgical Clinic University of L'Aquila from November 1986 to July 1990 with head trauma. The 5.6% (52 patients) had skull fractures. 23 (2.4%) patients sustained significant intracranial sequelae from their injuries, but only 4 (17.3%) of these also sustained fractures, 17 did not. Of the four fractures 1 were simple, 2 was depressed and 1 was basilar. The patients (17) without a skull fracture and positive CT were transferred to a neurosurgical department, where 12 underwent operation. The patients (4) with a skull fracture and positive CT and 2 patients with a depressed skull fracture and negative CT were transferred to a neurosurgical department where 5 (except 1 patient with simple fracture) underwent operation. The severity of coma was evaluated according to Glasgow Coma Scale (G.C.S.). The 2.4% of patients had the Glasgow Coma Scale = or less than 7. The CT or MNR are indicate in the presence of neurologic abnormalities. Overall mortality rate was about 0.53%. In the severe head trauma (G.C.S. = or less than 7) was of 17,3. IN CONCLUSION: the skull radiography is not indicated of routine and are performed for the evaluation of depressed fractures, of fracture of the cranial base and of cervical vertebrae: the MNR was found to be superior to CT and to be very effective in the detection of traumatic head lesions: the Glasgow Coma Scale is important for monitoring, stratification and prognostic evaluation of patients. PMID- 1503374 TI - [Intermuscular and intramuscular lipomas of the neck]. AB - Two cases of deep lipomas of the neck developed between the skeletal muscles were presented: one intermuscular and the other intramuscular. Taking into consideration the rarity of the case, the authors examined the clinical surgical aspect, paying special attention to the relationship between sonographic and computerized tomographic characteristics and the histological aspects in order to define whether the lipomatous tumors were benign or malignant. They also studied the localization of cervical lipomas, of lipoblastomas of hibernomas and of liposarcomas and defined an anatomo-clinical classification of both superficial and deep cervical lipomas. PMID- 1503375 TI - [Extensive lymphadenectomy and long-term survival in right hemicolectomy for carcinoma]. AB - Late clinical outbreak in patients with right colon cancer translates into very advanced stage of the tumour. Nevertheless, long term results of radical surgery are favourable, even if susceptible of improvements. While earlier diagnoses are not easy to achieve, a greater surgical radicality can be obtained both by extending resections to the surrounding structures and organs, and by enlarging lymphadenectomy to all the inframesocolic compartment and to the main lymph nodes located at the level of superior mesenteric vessels. A series of 60 right hemicolectomies performed from 1968 to 1990 to treat right colonic cancer is presented. Intraoperative mortality was of 4 cases (6.6%). Lymph node "mapping" was drawn, and in 26 cases (43%) metastases were found. Paracolic nodes were involved in 96% of cases, intermediate in 42%, and principal ones in 34%. Forty four patients, surgically treated up to 1985 and eligible for a 5 year follow up, were all verified. Overall free of disease survival was assessed in 28 cases (63.6%). Survival in relation to Dukes staging was 81.8% (9/11) in C. According to presence (LN+) or absence (LN-) of lymphatic spread, 5 year survival was found to be 70.3% (19/27) in LN-, and 52.9 (9/17) in LN+. Difference between the two groups is 17.4%, much smaller than the mean one of 45% reported by world literature. This figure, together with the finding of a 12, 10 and 5 year survival in patients with principal nodes involvement, suggests that extended lymphadenectomy might play a principal role in improving long term survival rates of advanced right colon cancer. PMID- 1503376 TI - [A new fluid-jet dissector in hepatobiliary surgery]. AB - Increasing experience with major hepatic resections has stimulated the development of improved resectional techniques and tools. The authors describe a recently developed high pressure, high velocity water jet which offers significant advantages over previously developed methods like ultrasonic dissectors and low pressure water jet machines. The pressure of the system is significantly elevated (between 200 and 600 Bars) and the ejection speed is over 300 m/sec. although the flux remains low. It has been successfully used in 22 major hepatic resections (2 left hepatectomy, 4 extended left, 3 right, 8 extended right and 5 segmental resections) and also during 6 peripheral biliodigestive bypasses (3 segment III bypasses and 3 peripheral segment III bypasses). The blood loss was low and the visibility excellent. The amount of fluid required by the instrument was small reducing the risk of complications. Previous report demonstrated that the water jets are more effective when compared with ultrasound dissectors. The technical characteristic of the new high pressure water jet improves on those intrinsic qualities allowing a more rapid dissection of both fibrous and normal parenchyma and simplifying the use of the instrument. The authors conclude that the new high pressure, high velocity water jet is an effective tool for biliodigestive surgery. PMID- 1503377 TI - [Action of infrared laser on in vitro culture of fibroblasts: effects of the exposure time parameter]. AB - We have evaluated the effects of low dose laser radiation on in vitro grown fibroblasts. We have observed no differences between treated plates and no treated plates after modification of exposure time. PMID- 1503378 TI - [Use of microcomputers in biomedical research. Project and implementation of an analysis of variance program. Computer notes]. AB - Clinical and experimental numerical data evaluation requires microcomputer programs which greatly facilitate both the ease and speed of handling statistical data processing tasks. In present study designing and construction of variance analysis program is approached for application of computers to surgery. It is an approach which allows a physician who has some familiarity with programming techniques to rapidly construct and use a family of programs for statistical manipulation of numeric information. PMID- 1503380 TI - Commemorative issue. Professor Dato Dr Seah Cheng Siang (1922-1990). PMID- 1503379 TI - [Chemotherapeutic prophylaxis in the preparation of the large intestine for surgical interventions: rifaximin P.O. vs. cephalosporin I.V]. AB - 30 patients were examined: 17 males and 13 females aged between 53 and 83 years (average age 66 years), candidates for large intestine surgery. For 5 days before the operation, they were treated at random, in a balanced way, with cefotaxime (3 g/day intravenously), either alone or associated with rifaximin (1200 mg/day P.O.). Rifaximin, an antibiotic drug endowed with a topical intestinal action, substantially increased the antibacterial activity of the well known and traditional third-generation cephalosporins therapy in the prevention of bacterial infections after major colic surgery. Intestinal bacterial load and pathogenic micro-organisms reduction was substantially increased. Furthermore, a more limited onset of post- surgical complications was observed, together with a better post-surgical clinical course, and a more rapid recovery of normal intestinal functions. The possibility of carrying out an effective chemoprophylaxis by means of an oral drug, such as rifaximin, must be encouraged as, among other things, it substantially reduces the intolerance risk at systemic level, which is nevertheless possible with parenteral antibiotic treatments. PMID- 1503381 TI - The Inaugural Seah Cheng Siang Memorial Lecture: life and times of Seah Cheng Siang. PMID- 1503382 TI - Neonatal screening for biotinidase deficiency. AB - Children with juvenile-onset multiple carboxylase deficiency lack biotinidase activity (biotinamide amidohydrolase, EC 3.5.1.12) in the liver and other tissues. Hence, little free biotin is metabolically available, resulting in seizures, acidosis, and serious neurological damage. As the absence of hepatic biotinidase activity is reflected in serum, assessment of biotinidase status can easily be made from a blood sample. A convenient qualitative procedure for screening infants has been employed in order to estimate serum levels of biotinidase in as little as 10 microliters of sample. This colorimetric procedure detects the formation of free p-aminobenzoate cleaved from the substrate, N biotinyl-p-aminobenzoate at pH 6.0. The assay is easily performed and has a low incidence of false positive results. A kinetic assay for serum biotinidase has also been developed using biotinyl-p-nitroanilide (BpNA) as substrate. When 50 microliters of biotinidase positive serum was incubated with 0.2 mM BpNA in phosphate buffer at pH 6.0, an increase in absorbance was observed at 405 nm. The rate of change in absorbance was followed kinetically on the Roche Cobas BIO analyzer at 37 degrees C. Monitoring the increase in absorbance of para nitroanilide every 60 seconds over 30 minutes demonstrated linearity from 10 to 30 minutes. In comparing results from this kinetic assay on 48 randomly selected sera with those obtained using a colorimetric procedure, a correlation coefficient of 0.85 was obtained. Several false positive results were observed in clearly lipemic sera. PMID- 1503383 TI - Evaluation of a spectrophotometric method for measurement of activity of diamine oxidase in newborn infants. AB - Diamine oxidase (DAO) is an enzyme synthesized primarily in the gastrointestinal mucosal cells. Serum levels of DAO have been used as an indicator of the integrity and/or functional mass of the intestinal mucosa. The enzyme is also produced by the placenta and is elevated in newborn serum. Previous radiometric methods for DAO used tritiated putrescine or cadaverine as substrate. A simple and rapid spectrophotometric procedure for DAO with use of histamine as substrate was developed, and this assay was utilized to evaluate the developmental pattern of activity of DAO in umbilical cord blood of newborn full-term and premature infants, in sequential samples from premature infants, and in samples from infants with necrotizing enterocolitis. The spectrophotometric assay was linear to 200 U per L and was also precise with total imprecision (CV) of 11.9 percent and 3.7 percent at DAO activities of 25.6 U per 1 and 126.1 U per L, respectively. Triglycerides above 275 mg per dL caused a significant reduction in measured activity of DAO; however, this effect could be eliminated by use of ultracentrifugation to remove lipemia. Plasma samples with heparin or ethylenediamine tetraacetic acid (EDTA) as anticoagulant were unsuitable for analysis since DAO activity showed a 24 percent and 32 percent decrease in activity at concentrations of 20 U per mL (heparin) and two mg per mL (EDTA), respectively. Serum samples are the specimen of choice. In infants it was found that the serum activity declined to adult levels by day 12 of life and that this decline is not affected by necrotizing arterocolitis. PMID- 1503384 TI - New methods for assessing liver function in infants and children. AB - Assessment of liver function in infants and children has traditionally relied on static indices of hepatic structure, cellular integrity, or function and are often based on the release of substances from damaged tissues. There has been a rapid development of dynamic tests based on the measurement of substances metabolized or cleared from blood by the liver. These tests, which have been touted to offer a more precise quantitative estimation of hepatic functional capacity, include the measurement of serum bile acids and the hepatic metabolism of xenobiotic compounds such as caffeine and lidocaine. Serum bile acid measurements appear to be reliable indicators of enterohepatic circulation and may be useful in screening for liver disease. It has been observed that caffeine metabolism is decreased in patients with various forms of liver disease in correlating with disease status. Caffeine has the advantage of being well tolerated when administered orally; the saliva level parallels the serum concentration, making a non-invasive test feasible. Lidocaine is metabolized by oxidative de-ethylation to monoethylglycinexylide (MEGX); analysis of MEGX by common laboratory instrumentation makes rapid evaluation of liver function possible. The MEGX values correlated were with pretransplant liver disease assessment. These tests are currently being evaluated at other centers and, if the initial studies are repeated, they offer the hope for reliable dynamic tests of hepatic function. PMID- 1503385 TI - Pathological evaluation of WR-151327 administered orally in irradiated and non irradiated male mice. AB - Studies were made on the radioprotective and toxic effects of orally administered WR-151327 in male CD2F1 mice. The lowest dose of orally administered drug permitting probit analysis of data was 450 mg per kg. The calculated radioprotective dose reduction factors (DRF) at 450 mg per kg and 900 mg per kg of body weight (BW) WR-151327 were 1.2 and 1.3, respectfully. Pathological examination at 8, 30 or 90 days post administration of 100, 450, or 900 mg per kg of the drug demonstrated that the major target organ for orally dosed mice was the testes. There was a decrease in the number of cells in the germinal cell layers of testes from animals administered 450 mg per kg WR-151327 or 10 Gy whole body irradiation after eight days. Moreover, there was a dramatic reduction in the germinal cells in mice seminiferous tubules treated with a combination of 450 mg per kg WR-151327 plus 10 Gy radiation after eight days. PMID- 1503386 TI - The role of the laboratory in the use of biotech drugs: a call to arms. PMID- 1503387 TI - The effect of metal chelators on lipid peroxidation in stored erythrocytes. AB - Lipid peroxidation, an autocatalytic free radical process, is increased in a wide variety of conditions including various hemolytic anemias and hemoglobin disorders. Increased erythrocyte lipid peroxidation occurs in the presence of iron species and some heme moieties. In this study, greatly reduced concentrations of malondialdehyde (MDA), an indicator of lipid peroxidation, were observed in stored blood anticoagulated with citrate, phosphate, dextrose, and adenine (CPDA-1) upon the addition of deferoxamine mesylate (DM), diethylenetriaminepentaacetic acid (DTPA), and ethylenediaminetetraacetic acid (EDTA) (P less than 0.001). Human transferrin has essentially no effect on lipid peroxidation. Conversely, penicillamine and butylated hydroxytoluene significantly increased lipoperoxide production. Although bathophenanthroline disulfonic acid (BPD) appeared to be very effective in reducing lipid peroxidation, its complex chromatographic patterns which were due to the presence of multiple thiobarbituric acid reactive substances, were difficult to fully evaluate. The addition of appropriate metal chelators to stored blood may be effective in increasing the viability and longevity of transfused red cells. PMID- 1503388 TI - Lipoperoxides in sebum of substance users and controls. AB - Sebum was collected from forehead skin in five compulsive heroin and/or cocaine (substance) users and in five controls over three consecutive periods, each lasting three hours. The participants were adult black and white men similar in age and smoking habits, who did not consume alcohol. Lipoperoxides were determined in sebum as malondialdehyde by high performance liquid chromatography. Two participants were excluded in the control group: in both, urinary lipoperoxides were elevated; in one, urine tested positive for delta-9 tetrahydrocannabinol (THC). All other participants had negative urine drug screening tests. Relative to the controls, all substance users had elevated concentrations of lipoperoxides in urine. Compared to the controls, the rate of sebum excretion in the last collecting period was higher in substance users, but sebum had significantly lower lipoperoxide concentration. It is assumed that compulsive drug use may influence lipoperoxidation of incipient sebum, possibly by altered tissue perfusion. PMID- 1503389 TI - Munchausen sickle cell painful crisis. AB - A 22-year-old female with factitious sickle cell anemia and recurrent painful crises is described. Because she had sickle cell trait and iron deficiency anemia, she could successfully feign the symptoms of homozygous sickle cell anemia. The identification of this syndrome in patients with genetic disorders is presented. PMID- 1503390 TI - Whole blood viscosity in beta thalassemia minor. AB - Patients with heterozygous beta-thalassemia minor have a decreased hematocrit (HCT). Since the HCT is a primary determinant of whole blood viscosity, the known reduction in HCT in beta-thalassemia minor should lead to a measurable reduction of whole blood viscosity. The influence of the relatively lower mean corpuscular volume and consequent higher red blood cell count and beta-thalassemia minor on whole blood viscosity using a microporous viscometer has not previously been the subject of investigation. Accordingly, the blood of a group of normal and beta thalassemia minor subjects was examined with a microporous viscometer to elucidate further the relations between whole blood viscosity, HCT, and red blood cell count. The data show that for normal and beta-thalassemia minor subjects a significant positive correlation (r = 0.65, p less than 0.01) exists between HCT and whole blood viscosity. However, the slope of the regression of whole blood viscosity and HCT of beta-thalassemia minor subjects was significantly higher z = 3.14, p less than 0.001) than that of normals. Thus, for any given HCT their whole blood viscosity was higher than that of normals. Studies of the relation of red blood cell counts to whole blood viscosity indicate the higher whole blood viscosity at a given HCT was related to the increased red blood cell counts in beta-thalassemia minor subjects. Because of the opposing interactions of HCT and red blood cell counts, the mean whole blood viscosity of the group of beta thalassemia minor subjects examined was not significantly lower than the normal whole blood viscosity.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1503391 TI - The fluorescent calcium indicator indo-1/AM inhibits renal proximal tubule cell volume regulation. AB - The intracellular calcium indicator, indo-1, is a fluorescent compound related in structure and function to the calcium chelator ethylene glycol-bis(beta aminoethyl ether) tetraacetic acid (EGTA) that binds one calcium ion per molecule. In the extracellular range of 1 to 10 microM indo-1/AM, the estimated intracellular concentration of the dye is 0.1 to 3 microM. Therefore, it is likely that intracellular calcium signals could be blunted under these experimental conditions (Cai approximately 0.1 to 0.2 microM). To evaluate the potential effects of indo-1/AM on cellular function, proximal renal tubules of the teleost Carassius auratus (goldfish) were exposed to its acetoxymethyl ester (cell permeable form) in an isotonic Ringer's solution (290 mOsm, 0.1 mM calcium) followed by exposure to a low sodium hypotonic Ringer's (110 mOsm, 0.1 mM calcium). Cellular regulatory volume decreases (RVD) were determined with videometric methods. In proximal renal tubules incubated with indo-1/AM, RVD was inhibited in a dose-dependent fashion (3 to 5 microM). No effects on RVD were observed with the impermeant salt of indo-1. Overt cellular injury was found at 10 microM indo-1/AM as evidenced by mitochondrial and cell swelling, cellular detachment from the tubular basement membrane, and different degrees of cytolysis. It is postulated by us that the inhibitory effects of indo-1/AM (3-5 microM) on RVD are due to intracellular calcium chelation followed by disruption of intracellular signalling. PMID- 1503392 TI - Natural selection associated with birth weight. VI. Towards the end of the stabilizing component. AB - The secular trend for stabilizing selection on birth weight has been analysed in Italy from 1954 to 1985 in order to study changes in the forces of natural selection which have occurred as a consequence of progress in health care. In previous papers we demonstrated a very rapid relaxation of stabilizing selection on birth weight. In this paper we show that in the last few years this kind of selection has been coming to an end for the vast majority of Italian newborns. PMID- 1503393 TI - Bayesian methods and optimal experimental design for gene mapping by radiation hybrids. AB - Radiation hybrid mapping is a somatic cell technique for ordering human loci along a chromosome and estimating the physical distance between adjacent loci. The present paper considers a realistic model of fragment generation and retention. This model assumes that fragments are generated in the ancestral cell of a clone according to a Poisson breakage process along the chromosome. Once generated, fragments are independently retained in the clone with a common retention probability. Based on this and less restrictive models, statistical criteria such as minimum obligate breaks, maximum likelihood, and Bayesian posterior probabilities can be used to decide order. Distances can be estimated by either maximum likelihood or Bayesian posterior means. The model also permits rational design of radiation dose for optimal statistical precision. A brief examination of some real data illustrates our criteria and computational algorithms. PMID- 1503394 TI - Strategies based on marker information for the study of human diseases. AB - The goals and the ways of using genetic marker information when studying human disease are very different according to whether the disease or sub-entity of the disease is mendelian or if a 'disease gene' in the sense of a rare mutated allele does not exist but rather common genetic risk factors, each one normal if considered alone. In the former case, genetic markers are used in the aim of localizing the defective gene and a systematic screening of the genome seems to be an efficient strategy provided there is not too much ambiguity in the correspondence between phenotypes and genotypes. In the latter case, the goal is to find risk factors allowing us to predict better the risk for an individual and to define different risk groups resulting in greater power to show the potential role of other factors (genetic or environmental). In this situation, the use of the lod score method with random markers presents several disadvantages: first, the multiple testing problem is particularly crucial; second, false rejection of linkage may be induced by misspecification of the model describing the genetic basis of the disease; and last, the power of detecting linkage may be low. A strategy focusing on 'candidate gene' markers may be then more efficient. PMID- 1503395 TI - In the multifactorial model of disease transmission, why is the rank correlation sensitive to choice of bivariate distribution? AB - The multifactorial model uses a dichotomization (ill vs. well) that occurs in the extreme tail of a bivariate distribution. The crudeness of this is responsible for rank correlation - which is a summary statistic calculated from the whole bivariate distribution - being sensitive to the choice of the bivariate distributional form. PMID- 1503396 TI - Chromosomal assignment of human phenol and bilirubin UDP-glucuronosyltransferase genes (UGT1A-subfamily). AB - DNA probes were prepared from the 5'-terminal portion of four cDNA clones encoding human phenol and bilirubin UDP-glucuronosyltransferases (UGTs). An additional sequence common to all four clones was isolated from the 3'-terminal portion of one of the clones (UGT1A1). The four specific and the one common DNA sequences were used as probes on a panel of 16 human--rodent somatic cell hybrid DNAs by Southern-blot analysis. The results obtained indicate that all four cDNA clones are encoded by gene(s) located on human chromosome 2. PMID- 1503397 TI - Carrier detection of deletions of the Hunter gene by in situ hybridization. AB - Deficiency of the lysosomal enzyme alpha-iduronate sulphate sulphatase (IDS) causes the clinical manifestations of Hunter syndrome, an X-linked condition. In about 30% of male patients, the disease is due to a major deletion. Using a non isotopic in situ hybridization (NISH) method, and a yeast artificial chromosome (YAC) probe, the Hunter gene was mapped to the terminal region of the human X chromosome, close to the Xq28 band. The NISH procedure was then applied to investigate the carrier status of female relatives of a Hunter patient known to have a deletion of the IDS gene. Unequivocal evidence that two female relatives were carriers of the deletion was obtained, demonstrating that the NISH method is a valuable diagnostic tool in genetic counselling of families with Hunter patients. PMID- 1503398 TI - Dominant genes for colorectal cancer are not rare. AB - The genetic basis for colorectal cancer was investigated by complex segregation analysis of a published series of consecutive pedigrees ascertained through patients undergoing treatment for colorectal cancer. Analysis favoured a dominant gene or genes with a frequency of 0.006 with a lifetime penetrance of 0.63. These genes account for 81% of colorectal cancer in patients under 35, however, by 65 about 85% are phenocopies. PMID- 1503399 TI - Morphological and immunocytochemical characteristics of human tumor cell lines for use in a disease-oriented anticancer drug screen. AB - A panel of 60 human tumor cell lines is currently being used in the U.S. National Cancer Institute's in vitro anticancer drug screen. The panel is organized into 7 subpanels; 6 leukemia/lymphoma lines comprise one subpanel, and 54 other lines are organized into subpanels representing solid tumors of the central nervous system (CNS), colon, lung, ovaries, kidneys and melanomas. In the present study, the leukemia and lymphoma cell lines were analyzed by flow cytometry for appropriate CD antigens; all but 1 line showed patterns of expression consistent with their reported derivations. The solid tumor lines were characterized individually using morphological and immunocytochemical techniques to determine their relative degrees of representativity for the subpanels within which they are currently grouped. Histological, histochemical and ultrastructural examinations were performed on cell lines grown under identical conventional culture conditions and as xenografts in nude mice. Immunocytochemistry using panels of antibodies raised against 6 types of intermediate filaments, 7 adenocarcinoma-associated antigens, 7 melanoma/neuro-ectodermal-associated antigens, 3 neuroendocrine-associated antigens, 9 urinary tract associated antigens, and 4 markers of muscle differentiation was done on cells grown in monolayer culture. Central nervous system (CNS) cell lines lacked expression of glial fibrillary acidic protein, but all had other features consistent with derivation from glioblastoma. Lines derived from adenocarcinomas of the colon, lung and ovary, for the most part, expressed adenocarcinoma-associated antigens and showed histological and/or ultrastructural evidence of gland formation and other adenomatous features. Most of these lines were poorly differentiated. Lines derived from large-cell and squamous-cell cancers also showed some characteristics consistent with their reported origins, except for one line which showed immunocytochemical and morphologic characteristics consistent with rhabdomyosarcoma. The 2 lines derived from small cell lung cancer (SCLC) lacked neurosecretory granules and 3 other SCLC markers but showed morphologic features consistent with SCLC. Most melanoma cell lines strongly expressed melanoma associated antigens and were morphologically similar to human melanoma. Five lines produced premelanosomes, melanosomes or melanin. Most of the renal cancer cell lines showed morphologic or immunocytochemical features consistent with renal clear cell carcinoma. Collectively, these morphological and immunocytochemical analyses provide information concerning tissue of origin, tumor type, degree of differentiation and other biologic features essential to the use of these lines in a disease-oriented in vitro antitumor drug screen and to the interpretation of data derived therefrom. PMID- 1503400 TI - Differential effects of the spermine analog, N1, N12-bis(ethyl)-spermine, on polyamine metabolism and cell growth in human melanoma cell lines and melanocytes. AB - We have previously found that in one of two human melanoma cell lines, potent increase in the polyamine catabolizing enzyme, spermidine/spermine N1 acetyltransferase (SSAT), correlate with growth sensitivity to the spermine analog, N1, N12-bis(ethyl) spermine (BESPM). Herein, we examine the generality of this SSAT response among seven human melanoma cell lines (LOX, SH-1, STO-1, HO, PANUT-3, MALME-3 and Ebey) and normal melanocytes and further evaluate its possible correlation with growth sensitivity. Following treatment with 10 microM BESPM for 48 hr, SSAT activity among the various cell lines increased from basal levels of 20-90 pmol/min/mg to levels ranging from 170 to 30,470 pmol/min/mg. Five of the seven cell lines and melanocytes induced SSAT activity to levels to greater than 2,500 pmol/min/mg and three of these, to levels greater than 10,000 pmol/min/mg. When ranked according to SSAT responsiveness (LOX less than SH-1 less than STO-1 less than HO less than PANUT-3 less than MALME3 less than Ebey), there was a general correlation among the cell lines with growth sensitivity. Antiproliferative effects ranged from slowing of cell growth in the less SSAT responsive lines (LOX, SH-1) to total cessation of cell growth or overt cytotoxicity in the more potently SSAT responsive lines (MALME-3, Ebey). The polyamine biosynthetic enzyme activities, ornithine and S-adenosylmethionine decarboxylase, were similarly suppressed in all cell lines, presumably via analog activation of inherent regulatory mechanisms. Polyamine pool reduction occurred to a greater extent than predicted in cell lines where SSAT was increased to greater than 2500 pmol/min/mg suggesting a possible role for the enzyme in enhancing polyamine excretion and/or catabolism. The occurrence of potent SSAT induction among several human melanoma cell lines and the growth sensitivity of these same lines to BESPM suggests that the enzyme response may represent a determinant of drug action in this particular malignancy. PMID- 1503401 TI - Antineoplastic activity of boron-containing thymidine nucleosides in Tmolt3 leukemic cells. AB - The sugar boronated thymidine nucleoside, 5' -0-[(triphenylphosphine-boryl) carbonyl]-3'-0-acetyl thymidine 1, and the boron-modified nucleoside phosphotriester, 5'-(diethylphosphite- cyanoborane)-3'-acetylthymidine 2, were successfully synthesized. Both compounds demonstrated differential activity when tested against eight cell lines, with significant cytotoxic activity against the growth of human Tmolt3 leukemia, colon adenocarcinoma, HeLa S3 uterine carcinoma, and osteosarcoma cells. In in vivo studies these agents were found to be active against the growth of Ehrlich ascites carcinoma at 8 mg/kg/day I.P. and to be marginally active against the growth of L1210 and Lewis lung cancers in mice. The mode of action of these thymidine derivatives in Tmolt3 cells was the inhibition of DNA and protein synthesis. Compound 2 was highly effective in inhibiting DNA polymerase alpha and m-RNA, r-RNA and t-RNA polymerase activities. Both compounds inhibited ribonucleoside reductase activity. The de novo purine pathway appeared to be the major site of inhibition of the agents, with IMP dehydrogenase, PRPP amido transferase, and dihydrofolate reductase activities being significantly inhibited. In the pyrimidine pathway, carbamyl phosphate synthetase and aspartate transcarbamylase activities were inhibited by 1. As expected, d[NTP] levels were significantly reduced by treatment with the agents. DNA strand scission was evident after incubating Tmolt3 cells for 24 hr with the agents. PMID- 1503402 TI - Application of anti lung adenocarcinoma monoclonal antibody recognizing cytokeratin-like cytoplasmic antigen for tumor diagnosis. AB - An anti lung adenocarcinoma murine monoclonal antibody (MoAb), KM195 (IgG1), was generated using mice which underwent tolerance treatment to normal lung tissues. KM195 was selected from among a number of hybridoma clones because of its advantageous reactivity such as high binding to cell membranes of lung adenocarcinoma tissues and low binding to cell membranes of major normal tissues. In a binding assay using cultured cell lines KM195 was found to bind cytoplasmic antigen in many adenocarcinoma cells. Detailed immunohistochemical analysis using paraffin-fixed tissue sections showed that many adenocarcinoma cells such as gastric cancer, colorectal cancer, pancreatic cancer, mammary cancer, ovary cancer and cervical cancer reacted positively with KM195, as well as lung adenocarcinoma cells. KM195 also positively stained a small number of normal cells found in adult and fetal tissues like lung, intestine, pancreas, liver and kidney. Western blot analysis using membrane fraction of lung adenocarcinoma tissues revealed two major KM195-positive bands which were electrophoresed nearby at molecular weights (M.W.) of 40 Kd. The protein corresponding to the two major bands was purified by immuno-affinity chromatography and sequenced. The amino terminal 19 residues of the lower band was identified as VLEVDPNIQAVXTQEXEQI, which is identical to that of the human cytokeratin 8 (residues 77 to 95), M.W. 52Kd. The amino-terminal sequence of the upper band was blocked and not determined. To examine the ability of KM195 for tumor imaging, 125I-labeled KM195 was injected i.v. into nude mice bearing SW1116 xenografts. Significantly higher radioactivity was observed in the tumor compared with major organs at days 3 and 5. These data indicate that KM195, which recognizes cytokeratin 8-like cytoplasmic antigen, could be a potential MoAb for use in the immunohistochemical diagnosis and radioimmunodetection of adenocarcinoma. PMID- 1503403 TI - Combined radioimmunotherapy and chemotherapy of human colon carcinoma grafted in nude mice, advantages and limitations. AB - In order to determine if 5-fluorouracil (5FU) could potentiate the effect of radioimmunotherapy (RIT), nude mice bearing subcutaneous human colon carcinoma xenografts were treated by 1 or 2 intravenous injection(s) of subtherapeutic doses of 131I labeled F(ab')2 from anti-carcinoembryonic antigen monoclonal antibodies combined with 5 daily intraperitoneal injections of 5FU. Control mice received either 131I F(ab')2 alone, 5FU alone or no treatment. RIT alone induced significant tumor regression, while 5FU alone gave only minimal tumor growth inhibition. The combined treatment group also resulted in long-term tumor regression with tumors remaining significantly smaller than in the RIT alone group. There was however, no significant difference in tumor recurrence time between the groups treated with RIT alone or with RIT + 5FU. Myelotoxicity, the major side effect of RIT, detected by the decrease of peripheral white blood cells (WBC), was shown to be almost identical between the groups receiving only RIT or only 5FU. Surprisingly, there was no cumulative bone marrow toxicity in animals which received 5FU before RIT. Furthermore, in the latter group, the WBC levels after RIT were significantly higher than in the control group receiving only RIT. Taken together, the results demonstrate the higher therapeutic efficiency of RIT as compared to 5FU in this model. They do not show, however, that the combination of the two forms of treatment can induce longer tumor remission. Interestingly, the WBC results suggest that 5FU given before RIT can have a radioprotective effect on bone marrow, possibly by selecting radioresistant bone marrow stem cells. PMID- 1503404 TI - Inhibitory effects of physalin B and physalin F on various human leukemia cells in vitro. AB - Physalins B and F were isolated and characterized from the ethanolic extract of the whole plant of Physalis angulata L. (Solanaceae). Both physalin B and physalin F inhibited the growth of several human leukemia cells: K562 (erythroleukemia), APM1840 (acute T lymphoid leukemia), HL-60 (acute promyelocytic leukemia), KG-1 (acute myeloid leukemia), CTV1 (acute monocytic leukemia) and B cell (acute B lymphoid leukemia). Physalin F showed a stronger activity against these leukemia cells than physalin B, especially against acute myeloid leukemia (KG-1) and acute B lymphoid leukemia (B cell). From the structural features, the active site seems to be the functional epoxy group for physalin F and the double bond for physalin B located at carbon 5 and 6; the former is much more active than the latter as regards anti-leukemic effects. PMID- 1503405 TI - Clonal drift and role of chromosome dosage in human melanoma metastatic cell lines: a statistical analysis. AB - Karyotypic analyses were performed on twenty human melanoma clones and variants all deriving, following in vivo selections and/or in vitro cloning, from the parental M4Be cell line, but expressing different tumorigenicity (expressed as mean tumor weight) and metastatic ability (expressed as pulmonary metastasis frequency) after s.c. injection in antithymocyte immunosuppressed newborn rats. These cells were hypertriploid, showing quite comparable modal numbers (around 70). They all expressed a wide range of chromosome number per mitosis (28 to 198), as well as a large extent of karyotypic heterogeneity, showed by extensive clonal drifts within the different cell lines. Their common origin was ascertained by five clonal abnormal marker chromosomes deriving from chromosomes 6, 7, 8, 9, 11 and 14. Twenty-one additional marker chromosomes, most of them non clonal, were observed in the different cell lines. We developed a statistical analysis to search for putative relationship between the expression of tumorigenicity and metastatic ability and the evolution of specific subclones within the different cell lines. We showed that the expression of a high mean tumor weight and/or a high metastasis incidence was related to the modification of the ratio of different subclones within each cell line, and more especially to the emergence of subclones presenting partial losses of individual chromosomes or chromosomal fragments, which were encountered with a lower frequency in the low metastatic cell lines. The biological relevance of these findings in terms of clonal evolution and role of chromosome dosage in tumor progression is discussed. PMID- 1503406 TI - Prognostic relevance of DNA ploidy in rhabdomyosarcomas and other sarcomas of childhood. AB - A study of DNA content by flow cytometry revealed a significant difference between rhabdomyosarcomas, which were mainly non-diploid, and other sarcomas of children which were mainly diploid (p = 0.01). There was no association between DNA ploidy and survival or aggressive behaviour of the tumour as indicated for example by advanced clinical stage or unfavourable histology. While DNA ploidy correlated with age, it did not correlate with any other clinical characteristic. The apparent lack of prognostic value of DNA content may have been masked by some high CV values and overridden by the effect of chemotherapy which was the most significant variable in determining a patient's survival (p = 0.00005). PMID- 1503407 TI - Expression of EGF, TGF-alpha and EGFR in squamous cell lung carcinomas. AB - Immunohistochemical study of epidermal growth factor (EGF), epidermal growth factor receptor (EGFR) and transforming growth factor-alpha (TGF-alpha) expression was performed on paraffin-embedded tissue specimens of 70 squamous cell lung carcinomas. The carcinomas were placed to one of the following eight groups, according to the results of EGF, TGF-alpha and EGFR expression: group 1: none, group 2: only EGFR, group 3: EGFR and TGF-alpha, group 4: EGFR and EGF, group 5: TGF-alpha and EGF, group 6: all three, group 7: only TGF-alpha and finally group 8: only EGF. Statistical analysis of the results revealed that the ratio of squamous cell lung carcinomas with lymph node metastasis was significantly higher in groups 4, 5 and 6 (P less than 0.01). We also examined whether EGF receptors were truncated with the use of two monoclonal antibodies directed against different portions of the receptor (EGFR1 and F4). No truncated EGF receptors were detected. These results suggest that lung carcinomas expressing the molecules EGF/EGFR, TFG-alpha/EGFR or TGF/alpha/EGF/EGFR display pathologic features of more aggressive disease. PMID- 1503408 TI - Immunohistochemical analysis of the ras p21 oncoprotein in Hashimoto's thyroiditis. AB - We studied the ras oncogene expression using immunohistochemical detection of p21 oncoprotein in paraffin-embedded tissue sections or fine needle aspiration (FNA) material from 25 patients with Hashimoto's thyroiditis and 12 healthy individuals. We also investigated the presence of this protein in the lymphocytes of thyroid gland, as well as in peripheral blood lymphocytes. We found increased expression of p21 oncoprotein by thyroid epithelial cells in 22 patients (intensity of staining ++), whereas we observed negative or slightly positive in 9 and 3 out of 12 normal controls, respectively (intensity of staining, - or +/ ). We also detected p21 oncoprotein in moderate amounts in patients' intrathyroid lymphocytes (intensity of staining +), but peripheral blood lymphocytes did not present any staining result. Our findings provided evidence that epithelial cells, as well as lymphocytes infiltrating the thyroid gland, are probably "activated" in Hashimoto's thyroiditis. The significance of this "activation" in thyroid tumorigenesis remains unknown. PMID- 1503410 TI - Antimicrobial activity of phenothiazines, benzo[a]phenothiazines and benz[c]acridines. AB - The abilities of 14 phenothiazines, 8 benzo[a]phenothiazines and 12 benz[c]acridines to induce an antibacterial effect against Escherichia coli K12 were compared. Several phenothiazines, which showed antiplasmid activity, displayed the most potent antibacterial activity. All benz[c]acridine derivatives were moderately antibacterial, whereas benzo[a]phenothiazines were inactive. The active phenothiazine derivatives had more potent inhibitory activity against fungi, including phytopathogen filamentous, human pathogen filamentous fungi and yeasts, than against gram-positive and -negative bacteria. Taken together with previously reported data, the induction mechanism of antimicrobial and antiplasmid activity by these compounds seems to be different from that of antitumor, differentiation-inducing and carcinogenic activity. PMID- 1503409 TI - An inducible cell line (Natasha), from a neuroblastoma patient with circulating HSR-positive blasts, expressing neurohormones. AB - A cell line, established from a neuroblastoma patient, expresses NCAM and L1 cell adhesion molecules. Two chromosomal abnormalities were present in bone marrow (10%) and cell line (82%) metaphases: (i) a homogeneously staining region (HSR) at the distal part of chromosome 14, and (ii) an insertion of unidentified dark G banding material in 1 p36. The identification in the patient of chr 14-HSR positive tumour cells, before the in vitro adaptation, suggests a direct HSR formation without preceding double minutes (dms; or a very early in vivo dms--- HSR transformation). N-myc was amplified in the HSR. Cells expressed proopiomelanocortin and corticotropin releasing factor mRNAs. Untreated cells were relatively differentiated; nevertheless they dramatically responded to retinoic acid, forming extensive neurites, growth-cones, cell-cell and cell neurite junctions. Neurofilaments and synaptic figures containing many dense core granules were identified. This differentiation was irreversible. This cell line is therefore useful for the study of differentiation and in particular for the involvement of neurohormones in the differentiation process. PMID- 1503411 TI - The effect of Ganoderma lucidum on induction of differentiation in leukemic U937 cells. AB - Ganoderma (G.) lucidum is a herbal medicine with tumoricidal activity capable of inhibiting the proliferation of mouse Sarcoma 180 cells both in vitro and in vivo. In this study, we investigated the effect of the polysaccharide fraction of G. lucidum (PS-G) on the proliferation and differentiation of human monocytic leukemia cell line, U937. Using an in vitro liquid culture system, we found that the conditioned medium from PS-G-stimulated human blood mononuclear cells (PSG MNC-CM) contained an activity that could significantly inhibit the growth of U937 cells and induce them to differentiate into mature monocytes/macrophages which had functions of phagocytosis and producing cytoplasmic superoxide. Neither PS-G nor normal (untreated) MNC-CM was found to have a differentiating effect on the target cells. The optimal condition for stimulating the in vitro production of MNC-derived differentiation-inducing activity was to use PS-G at a low concentration of 50 micrograms/ml and to incubate MNC for a short period of 24 hours. Long-term (greater than 3 days) incubation resulted in a decrease in the differentiating activity of the conditioned media. PMID- 1503412 TI - Differential surface structures of invasive and non-invasive Ehrlich ascites tumor cell lines with special reference to the effect of hydrocortisone treatment. AB - The purpose of this study is to investigate the relation between the fine structure of the tumor cell surface and the tumor malignancy by scanning electron microscopy. Practically, comparison was made between the invasive Ehrlich ascites clone 1 tumor and the non-invasive Ehrlich ascites clone 3 tumor, and also between the 4th postinoculation day and the 6th postinoculation day as regards the growth of microvilli on the cell surface. On the 4th postinoculation day, an invasive clone 1 tumor cell was indistinguishable from a non-invasive clone tumor cell because of their common paucity of microvilli development. On the 6th postinoculation day, the former was associated with exuberant growth of microvilli, and was clearly distinguished from the latter in which the density of microvilli stayed low as before. The appearance of dense microvilli growth in the invasive clone 1 tumor cells chronologically coincided with the stage of fatal bleeding into the abdominal cavity. Hydrocortisone with a dose of 1 mg/mouse, when given subcutaneously to a tumor-bearing mouse on the 4th postinoculation day, stimulated the development of microvilli in both clone 1 and clone 3 tumors. The enhancing effect of the hormone on this process was detectable 2 hours after hormone injection. It was indicated that the dense growth of microvilli in the clone 1 tumor facilitated its tumor invasion into visceral organs, and that the enhancing effect of hydrocortisone on microvilli development was to be related to the promotion of malignant transformation. The possible implications of glucocorticoid in mammocarcinogenesis are discussed from the point of view of comparative endocrinology. PMID- 1503413 TI - Proton NMR spectroscopy of plasma lipoproteins in the experimental Lewis lung carcinoma. AB - Plasma and fractionated lipoproteins from 40 Lewis Lung Carcinoma grafted mice were tested from the first day up to the fatal issue by biochemical analyses and water suppressed 1H NMR spectroscopy. We have confirmed first, that the 1H NMR spectra of plasma lipoproteins are modified by the tumoral state and could provide a useful marker of the disease as long as they are used for individual follow-up with appropriate spectral parameters. Using fractionated lipoproteins we have demonstrated secondly, that the observed spectral modifications do not result from a specific cancer lipoprotein but from quantitatively modified ratio between Very Light Density Lipoproteins and High Density Lipoproteins. PMID- 1503414 TI - Resistance of MGH-U1 bladder cancer spheroids to vincristine. AB - We compared the cytotoxicity of vincristine in MGH-U1 human bladder cancer cells growing as exponential monolayer culture, spheroids and xenografts. Cells treated as spheroids were resistant to vincristine as determined by clonogenic survival and growth delay. The spheroid population had a smaller proportion of cells in G2 + M than monolayer cells. Cell derived from increasing depths of the spheroid viable rim had similar cell cycle distribution characteristics and sensitivity to vincristine. Prolonged treatment of spheroid did not increase vincristine cytotoxicity significantly. When cells derived from spheroids were treated as monolayers, the cytotoxicity was the same as that of cells maintained as monolayer cultures. The vincristine resistance observed in spheroids was also observed in xenografted tumours treated in vivo. Vincristine decreased the clonogenic survival of xenografted cells at in vivo doses which were greater than the LD10 for the mice. The in vitro cytotoxicity of the xenografted tumours at these lethal doses was similar to that of cells treated as spheroids. We conclude that vincristine resistance in spheroids may be attributed in part to the small proportion of cells traversing mitosis but not to the development of intrinsic resistance by passage through spheroid growth. Our results are consistent with cell cycle kinetics and limited penetration contributing to vincristine resistance in spheroids. The spheroid system can serve as a model of in vivo cytotoxicity for antineoplastic agents with cell cycle phase specificity such as vincristine. PMID- 1503415 TI - Breast cancer in young women: clinical, histological and morphometric prognostic factors. AB - Clinical features, 8 histological features, 7 nuclear morphometric variables and 2 mitotic indices were entered in a univariate and in a multivariate survival analysis to assess their independent predictive value in 56 breast cancer patients under the age of 40 years who were followed up for over 10 years. The most important predictor of recurrence-free survival (RFS) in univariate analysis was the SD of nuclear perimetry (p = 0.003) followed by SD of nuclear area (p = 0.006), M/V index (p = 0.036), pN status (p = 0.046), nuclear area of 10 largest nuclei (p = 0.07), nuclear perimetry (p = 0.09) and nuclear area (p = 0.09) in that order. In pN(-) patients, SDPE (p = 0.04), SDNA (p = 0.07) and NA10 (p = 0.07) predicted RFS. In pN+ patients the most important predictor of RFS was the SDNA (p = 0.001) followed by NA 10 (p = 0.003), SDPE (p = 0.009), PE (p = 0.01), NA (p = 0.01) and Dmin (shortest diameter) (p = 0.04). In multivariate analysis the pN-status independently predicted RFS. Tumour size (p = 0.001), pN status (p = 0.002) and M/V-index (p = 0.079) were related to BS (breast cancer survival). In pN-patients, NA 10 (p = 0.097) predicted BS, whereas in pN+ tumours tumour size (p = 0.06) was the most important predictor of BS. In a multivariate analysis, tumour size (p = 0.02) and pN-status (p = 0.016) were independent predictors of BS. PMID- 1503416 TI - Properties of monoclonal antibodies to human tumor necrosis factor alpha (TNF alpha). AB - Four murine monoclonal antibodies were produced against human recombinant tumor necrosis factor alpha (TNF alpha). They were characterized with respect to specificity, affinity, neutralization of in vitro L929 cell killing by TNF alpha and neutralization of the in vivo biological activities of toxicity and tumor necrosis. The monoclonal antibodies were further investigated for reactivity with TNF alpha in Western blotting. All four monoclonal antibodies reacted with human TNF alpha. One of then also reacted with mouse TNF alpha and human TNF beta (lymphotoxin), this antibody did not neutralize in vitro cytotoxicity or in vitro biological activities of TNF alpha. The other antibodies were neutralizing and it appeared that, in some cases, the systemic toxic effect of TNF alpha could be reversed by anti-TNF alpha monoclonal antibody therapy while retaining significant anti-tumour effects. PMID- 1503417 TI - Squamous cell carcinoma antigen, tumor associated trypsin inhibitor and tissue polypeptide specific antigen in follow up of stage III cervical cancer. AB - 189 clinical and serological examinations were performed in 30 patients before treatment and during follow up of squamous cell cervical cancer stage FIGO III. The serum levels of the tumor markers squamous cell carcinoma antigen (SCC), tumor associated trypsin inhibitor (TATI) and tissue polypeptide specific antigen (TPS) were determined. Sensitivity/specificity for SCC was 63%/91%, TATI 54%/74%, TPS 59%/86% and for a combination of SCC and TPS 81%/77%. In 14 women with recurrence of disease SCC showed lead time effects in seven patients in a time range from three to nine months. SCC was pre-therapeutically elevated in nine cases and showed lead time in five of them. Pretherapeutic TPS serum levels were elevated in seven cases. In all of them lead time effects appeared ranging from three to nine months. TPS never showed lead time effects in patients without elevated pretherapeutic levels. A combination of SCC and TPS in our material provided lead time in 10 of 14 cases. PMID- 1503418 TI - Cell surface glycosylation and characterization of a differentially expressed glycoprotein in metastatic and non metastatic cell lines of the rat BSp73 tumor. AB - The highly (ASML) and non metastatic (AS) variants of the rat tumor BSp73 were compared with respect to cell surface carbohydrate proteins. Fluorescence labelling with lectins (ConA, MPA, PNA, SBA, UEA-I, WGA) revealed a differentiated carbohydrate pattern at the cell surface of these cell lines. The highly metastatic variant was significantly more glycosylated with respect to galactosyl, mannosyl and N-acetylgalactosylamine residues; fucosyl residues were exclusively expressed in the metastatic variant. Examination of isolated plasma membrane fractions showed quantitative differences with respect to glycosylated proteins separated on polyacrylamide gels. A 30 kDa glycoprotein (GP30-ASML) dominant in the metastatic variant was further characterized. Various detergents (CHAPS, Nonidet, SDS, Triton X-100) and urea extracted it exclusively from the highly metastatic variant. GP30-ASML is a predominantly O-glycosylated single polypeptide chain with terminal N-acetylgalactosamine and galactosyl residues; its molecular weight determined by SDS-PAGE is 30 kDa and its isoelectric point is 7.8. Immunofluorescence localization experiments with monoclonal antibodies specific for GP30-ASML and polyclonal antibodies raised against GP30-ASML showed this protein at the cell surface and in the lysosomal compartment of both cell lines; exclusively in the non metastatic variant it was also found in the nuclear membrane. The function of this protein is still unknown. PMID- 1503419 TI - Clinical evaluation of four tumor markers in malignant and benign pleural effusions. AB - Total sialic acid (TSA), lipid-bound sialic acid (LSA), ferritin and carcinoembryonic antigen (CEA) were evaluated in 55 patients with malignant pleural effusions and in 32 patients with benign (exudative) pleural effusions. No significant differences were found in the pleural fluid TSA, LSA and ferritin levels between malignant and benign conditions. CEA levels in malignant effusions were significantly higher than those in benign effusions (43.13 +/- 72.8 ng/ml versus 2.6 +/- 5.56 ng/ml, p less than 0.01). At a cut-off level of 5 ng/ml, 60% of the patients with cancer showed elevated pleural fluid CEA levels. The specificity and diagnostic accuracy of CEA in distinguishing malignant from benign pleural exudates were both very high (91% and 71% respectively). Therefore, of the four markers investigated, only CEA could be a valuable tool in the detection of pleural malignancy. PMID- 1503420 TI - Activity of CuDIPS against mammary cancer in C3H HeNCR mice. AB - A copper complex with superoxide dismutase mimetic activity, Cu(II)2 (3,5 diisopropylsalicylate)4 (CuDIPS), was tested for activity against mammary cancer in female C3H/HeNCR mice. Initiation of treatment at 20 or at 30 weeks of age had a limited beneficial effect on survival rates. Further, a small, but not statistically significant, difference in tumorigenesis was observed in comparisons between experimental and control groups of animals. Implications of these findings are discussed. PMID- 1503421 TI - Long-term effects of flavone acetic acid on the growth of a rat tumour. AB - A rat tumour (MC7 sarcoma), growing subcutaneously, has been shown to be sensitive to a single application of flavone acetic acid. Thirteen rats were still alive after 50 days and 8 of these were tumour free, as compared with control rats which survived for 15.7 +/- 2.53 days. The 8 tumour free animals were rechallenged with MC7 sarcoma 40 weeks later, without further FAA treatment. The tumour grew initially but in all cases the animals became tumour free within 24 days. After a further 30 days they were rechallenged with D23 hepatoma which grew as effectively as in the controls. PMID- 1503422 TI - Effects of different inducers of cytochrome P450 on the mutagenesis of the tobacco-specific nitrosamine 4-(methylnitrosamino)- 1-(3-pyridyl)-1-butanone (NNK) in Salmonella typhimurium TA1535. AB - The effects of six inducers of isoenzymes of cytochrome P450 on the mutagenicity of the tobacco-specific nitrosamine 4-(methylnitrosamino)-1-(3-pyridyl)-1 butanone (NNK) in Salmonella typhimurium strain TA1535 by hamster liver S9 and microsomes were investigated. Comparisons of the effects of dimethylsulfoxide (DMSO) as solvent for NNK were also made. The inducing agents were Aroclor 1254 (AROC), 3-methylcholanthrene (MC), phenobarbital (PB), dexamethasone (DXM), ethanol (ETOH) and isosafrol (ISF). The number of histidine-independent colonies induced by NNK in saline mediated by S9 from the inducing agents was as follows: ISF = AROC greater than PB greater than MC greater than DXM greater than ETOH. AROC-induced microsomes produced the most revertants by NNK (saline) greater than MC greater than PB = DXM and ISF greater than ETOH. The number of revertant colonies induced by NNK in DMSO was significantly less than that by NNK in saline for both hamster liver S9 and microsomes irrespective of the inducing agent. The greatest inhibitory effect of DMSO was observed with ISF-induced S9. PMID- 1503423 TI - Suppression by 1-(2-tetrahydrofuryl)-5-fluorouracil in combination with uracil of preneoplastic mammary hyperplastic alveolar nodule formation in SHN virgin mice. AB - It is known that hyperplastic alveolar nodule (HAN) is a representative preneoplastic state in mammary glands of mice. We examined the effect of 1-(2 tetrahydrofuryl)-5-fluorouracil and uracil (UFT) on HAN formation in a high mammary tumour strain of SHN virgin mice. Oral administration of UFT for 5 months beginning at one month of age significantly reduced the number of HAN and DNA synthesizing enzyme activities in the mammary glands. These results indicate that long-term administration of low dose UFT reduces the de novo and salvage synthesis of DNA and suppresses preneoplastic HAN. PMID- 1503424 TI - The role of additional chemotherapy with oral UFT in intravenous combination chemotherapy with cisplatin and 5-fluorouracil for human gastric cancer xenograft lines of well- and poorly- differentiated adenocarcinomas transplanted in nude mice. AB - In order to assess the role of maintenance chemotherapy with the oral anticancer agent UFT, a mixture of uracil and futraful, in the intensive intravenous chemotherapy for gastric cancer, nude mice transplanted with human gastric cancer xenografts were treated with intravenous 5-fluorouracil (5-FU) and cisplatin (CDDP), alone or in combination, with or without the oral anticancer agent UFT. UFT was given at its maximal clinical dose of 10 mg/kg of body weight daily for 2 weeks, while 5-FU and/or CDDP was intravenously administered at the dose of 20 mg/kg and 1.8 mg/kg of body weight respectively once a week, alone or in combination, for two weeks. The results revealed that 5-FU or CDDP alone were ineffective for both GC-YN, a well differentiated adenocarcinoma line, and GC-SF, a poorly differentiated adenocarcinoma line; however, UFT was effective for GC SF. In combinations, only the three-agent combination 5-FU + CDDP + UFT (FPU) was effective for GC-YN; however, all the two-agent combinations and FPU were effective for GC-SF. FPU significantly suppressed the growth of GC-YN much more than all the other treatment groups. In contrast, although all combinations as well as UFT alone were effective for GC-SF, there was no significant difference among these effective groups. Moreover, no side effects were noted in combined use of UFT. This study suggests that oral UFT as a maintenance treatment may be beneficial in the combination chemotherapy for human gastric cancer. PMID- 1503425 TI - Clinical analysis of cancer patients with bacteremia for the past ten years (1982 1991). AB - A trend in bacteremia associated with malignancies was studied in 159 cancer patients (pts) over the past ten years (1982-1991) in our university hospital. The proportion of female, aged persons and patients from the Int Med Dept had a tendency to increase in the later 5 years compared to the former 5 years. There was no significant change in proportion among G (+), G (-) and fungus groups. However, St. aureus has a tendency to increase among G (+) bacteria and Ps. aeruginosa among G (-) bacteria. The clinical features of the cancer patients with bacteremia were different depending on the types of organisms or kinds of underlying malignancies. PMID- 1503426 TI - Steroid receptors in breast cancer patients. Influence of obesity and age at diagnosis. AB - The influence of host age on estrogen (ER) and progesterone (PR) receptor status was studied in 603 tumors obtained from women with confirmed diagnosis of breast carcinoma. Both ER and PR analysis were performed in our own laboratory using standard techniques. Tumors were classified as positive if minimum receptor contents were greater than 10 fmol/mg cytosol protein and if dissociation constants were 1-9 x 10(-10) M or lower. Data from our study indicate that the incidence of receptor negative (ER-PR-) tumors was higher in women from 21 to 40 years of age than in women from 41 to 60 years of age. In women over 60 years of age, the incidence of ER+PR+ tumors was higher than in women under 40 years of age. Interestingly, women from 51 to 60 years of age had a significantly lower incidence (P less than 0.06, 0.0001) of ER+PR+ but higher incidence (P less than 0.01) of ER-PR- tumors than women 41-50 or greater than 60 years of age. Analysis of steroid receptor distribution in relation to host age and obesity showed a definite tendency: in obese women over 60 years of age, frequency of ER+PR+ was significantly greater than in non-obese women of similar age groups. This altered ER and PR distribution in tumors is probably a result of difference in the hormonal milieu associated with host menopausal status and obesity. PMID- 1503427 TI - Cervical smear total IgA in adenomatous polyp, dysplasia and carcinoma of the cervix. AB - Cervical smear total IgA (IgAc) concentration was determined in cervicitis and proliferative disorders of the cervical epithelium. All disorders except adenomatous polyp showed increased median IgAc levels as compared with healthy controls, in both the reproductive and the postmenopausal ages. In the former age group dysplasia exhibited the highest median IgAc level, while in the latter it ranked, second following specific cervicitis. Though differences between disease groups and controls were statistically non significant, they attained percent values as large as +277% (dysplasia, postmenopausal) and +596.9% (specific cervicitis, postmenopausal). Separate quantitation of the dimeric secretory and monomeric serum-derived components of total IgAc will provide more meaningful information. PMID- 1503428 TI - In vitro chemosensitivity testing of multilayered microcultures. AB - A potential limitation of in vitro microtiter cytotoxicity assays as compared to in vivo antitumor studies is that the complex three-dimensional structure of the solid tumor is lost in monolayer cultures in vitro. We investigated whether more in vivo like cell-cell interactions could be easily and reproducibly obtained in an in vitro cytotoxicity assay. HT29 human colon adenocarcinoma cells were seeded in 96-well microtiter plates with "V"-shaped wells and allowed to form postconfluent multilayered cultures. Cross-sections of microcultures fixed after 2 and 3 weeks following plating revealed approximately 7 and 35 cell layers, respectively. Using a tetrazolium assay to assess cytotoxicity, the EC50 (drug concentration which gives absorbance readings 50% lower than those of non-treated wells) of multilayered cultures exposed to doxorubicin for 24 h was 12 times higher (p less than 0.05) than that determined for subconfluent monolayered cells simultaneously exposed to the drug. This system offers an alternative to study the chemosensitivity of three-dimensionally organized cells using semiautomated microtiter plate technology. PMID- 1503429 TI - In vitro cytotoxicity of diorganotin (IV) trimethoxy-benzoates against sixty human NCl tumor cell lines. AB - Diethyl- and di-n-butyltin (IV) trimethoxybenzoates were tested in vitro at the National Cancer Institute, Bethesda, Maryland, USA, for cytotoxic activity against a panel of 60 human cell lines. The di-n-butylin compounds are more active in vitro against human tumor cell lines than their diethyltin analogs. PMID- 1503430 TI - The effects of steroid hormones on a human colon cancer cell line in vitro. AB - Estrogen analogues, moxestrol (10(-8)-10(-5) M) and ethinyl estradiol (10(-8)-10( 6) M), produced a 30% and 15% inhibition of LoVo cell growth, respectively, in serum-free Ham's F-10 medium. Under the same conditions, no growth effects were observed on these cells following the addition of progesterone or testosterone (10(-8)-10(-6) M); however, metribolone (10(-8)-10(-6) M), a synthetic androgen with glucocorticoid receptor-binding properties, moderately stimulated cell growth (18%). The synthetic antiandrogen, RU 23908 (10(-6) M), did not reduce metribolone effects, and hydrocortisone (10(-9)-10(-7) M) stimulated LoVo cell growth by 31% in serum-free medium. In medium containing 10% charcoal-treated fetal bovine serum, the inhibitory effects of estrogens were not observed, and the lower concentrations (10(-11) M) of moxestrol and ethinyl estradiol facilitated cell growth (10 to 15%). The other steroid hormones produced the same results as observed with serum-free medium. These data suggest that estrogen and glucocorticoid hormones may play an important role in the growth of colon carcinoma cells. Androgen and progesterone hormones appear to be less significant in this regard. Serum factors alter the effects of estrogen, but not of glucocorticoids. PMID- 1503431 TI - Active efflux mechanisms for antimicrobial resistance. PMID- 1503433 TI - Characterization of two plasmids from Campylobacter jejuni isolates that carry the aphA-7 kanamycin resistance determinant. AB - Two small plasmids of 11.5 and 9.5 kb, each carrying an aphA-7 kanamycin phosphotransferase gene, were studied. The MICs of kanamycin for the two human Campylobacter jejuni isolates harboring the plasmids were 10,000 and 5,000 micrograms/ml, while the MICs of amikacin were 32 and 8 micrograms/ml, respectively. The MICs of gentamicin and tobramycin were less than or equal to 2 micrograms/ml for both isolates. The restriction endonuclease maps of the plasmids were similar, with the larger plasmid showing two discrete regions of additional DNA. When the aphA-7 gene from each plasmid was cloned into pBR322, the aphA-7 gene expressed the kanamycin resistance phenotype in Escherichia coli. For transformants containing the cloned aphA-7 gene, kanamycin MICs were greater than or equal to 128 micrograms/ml. The aphA-7 gene was also subcloned from the plasmid pFKT4420 into the E. coli-Streptococcus shuttle vector pDL278 and was transformed into Streptococcus gordonii Challis. For streptococcal transformants containing the novel plasmid, kanamycin MICs were 4,000 micrograms/ml. In the presence of a tetracycline resistance plasmid, both small plasmids could be mobilized during conjugal matings to Campylobacter coli recipients. PMID- 1503432 TI - Molecular targets of 5-fluoroorotate in the human malaria parasite, Plasmodium falciparum. AB - 5-Fluoroorotate is known to have potent antimalarial activity against chloroquine susceptible as well as chloroquine-resistant clones of Plasmodium falciparum. It was hypothesized that this activity was mediated through synthesis of 5-fluoro-2' deoxyuridylate, an inactivator of thymidylate synthase, or through incorporation of 5-fluoropyrimidine residues into nucleic acids. Treatment of P. falciparum in culture with 100 nM 5-fluoroorotate resulted in rapid inactivation of malarial thymidylate synthase activity. A 50% loss of thymidylate synthase activity as well as a 50% decrease in parasite proliferation were seen with 5 nM 5 fluoroorotate. Dihydrofolate reductase activity, which resides on the same bifunctional protein as thymidylate synthase, was not affected by 5-fluoroorotate treatment. Incubation of malarial parasites with 3 to 10 microM radioactive 5 fluoroorotic acid for 48 h resulted in significant incorporation of radioactivity into the RNA fraction of P. falciparum; approximately 9% of the uridine residues were substituted with 5-fluorouridine. However, compared with the 50% inhibitory concentrations of 5-fluoroorotate, a 1,000-fold higher concentration of the pyrimidine analog was required to see significant modification of RNA molecules. Results of these studies are consistent with the hypothesis that thymidylate synthase is the primary target of 5-fluoroorotate in malarial parasites. PMID- 1503434 TI - In vitro susceptibilities of aerotolerant Campylobacter isolates to 22 antimicrobial agents. AB - We evaluated the in vitro activities of 22 antimicrobial agents against 78 human and animal isolates belonging to two aerotolerant Campylobacter species, C. cryaerophila and C. butzleri, using a broth microdilution technique. An additional 10 antimicrobial agents were included at concentrations found in selective Campylobacter media. Strains of C. cryaerophila belonged to two DNA hybridization groups: DNA hybridization group 1A, which includes the type strain of C. cryaerophila, and DNA hybridization group 1B. The aminoglycosides, fluoroquinolones, and one tetracycline (minocycline) demonstrated the most activity against all DNA hybridization groups (C. cryaerophila DNA groups 1A and 1B and C. butzleri). Most isolates were resistant to cephalosporin antibiotics, with the exception of cefotaxime, and were variably susceptible to trimethoprim sulfamethoxazole. C. cryaerophila DNA hybridization group 1A isolates were generally susceptible to the tetracyclines, chloramphenicol, nalidixic acid, azithromycin, erythromycin, and roxithromycin and moderately susceptible to clindamycin, trimethoprim-sulfamethoxazole, ampicillin, and ampicillin-sulbactam. The MICs of tetracyclines were higher for C. butzleri and C. cryaerophila DNA hybridization group 1B isolates than for C. cryaerophila DNA hybridization group 1A isolates, but most strains were still susceptible to doxycycline and tetracycline; all isolates were susceptible to minocycline. C. butzleri and C. cryaerophila DNA hybridization group 1B isolates were generally resistant to the macrolide antibiotics (including erythromycin), chloramphenicol, clindamycin, nalidixic acid, ampicillin, and trimethoprim-sulfamethoxazole. Differences in antimicrobial susceptibility between aerotolerant Campylobacter species and more common Campylobacter species, e.g., C. jejuni, suggest that different treatment strategies may be necessary. Strains of all three DNA hybridization groups of aerotolerant Campylobacter isolates were susceptible to colistin, polymyxin B, and rifampin at concentrations commonly used in selective media. These results suggest that primary isolation methods for Campylobacter species may need to be modified to include aerotolerant Campylobacter strains. PMID- 1503435 TI - Safety and efficacy of intranasal pirodavir (R77975) in experimental rhinovirus infection. AB - Pirodavir (R77975) is a capsid-binding, antipicornaviral agent with in vitro activity against most rhinovirus (RV) serotypes. We conducted four double-blind, controlled trials to assess the efficacy of intranasal pirodavir in experimentally induced RV infection of susceptible volunteers. Intranasal pirodavir (2 mg per dose) or the hydroxypropyl-beta-cyclodextrin vehicle as a placebo was given by metered pump spray. In three prophylaxis trials, subjects were inoculated with RV within 10 min of the second and third doses. When sprays were given six times per day for a total of 25 doses, infection, detected by either virus shedding or seroconversion, developed in 100% of the 13 placebo treated subjects and 58% of the 12 pirodavir-treated subjects (P = 0.015). Clinical colds developed in 54% of placebo-treated subjects and 8% of pirodavir treated subjects during drug administration (efficacy = 85%, P = 0.03), although late-developing colds developed in several subjects in both groups. Significant reductions in morning symptom scores and in the frequency of abnormal middle-ear pressures were also found in the pirodavir group. In contrast, in two prophylaxis studies using three doses daily, no significant antiviral or clinical benefits were observed. When frequent sprays were initiated at 24 h after RV challenge, significant reductions in virus shedding but no clinical benefits were found. Intranasal pirodavir was generally well tolerated but was associated with an excess rate of transient unpleasant taste. The findings indicated that frequent intranasal sprays of pirodavir were effective in preventing experimentally induced RV illness. PMID- 1503436 TI - Identification of factors affecting in vivo aminoglycoside activity in an experimental model of gram-negative endocarditis. AB - Aminoglycoside bactericidal activity during the first 24 h of treatment probably is a determining parameter in the prognosis of severe gram-negative infections in immunocompromised patients. To identify the predictive factors involved in the definition of the best therapeutic regimen for Enterobacter cloacae and Serratia marcescens infections, we studied different gentamicin, tobramycin, and amikacin regimens by using an experimental model of rabbit endocarditis. Two factors appear to play an important role in predicting in vivo efficacy: (i) the level of in vivo bactericidal activity, which can differ widely from one aminoglycoside to another for the same bacterial strain and from one strain to another of the same species, and (ii) the critical serum drug concentration (CSC, in milligrams per liter), defined as the lowest serum antibiotic concentration capable of producing a significant CFU reduction (P less than 0.05) in endocarditis vegetations 24 h after the beginning of a continuous infusion. Stepwise regression analysis showed that for gentamicin and S. marcescens, the area under the concentration-time curve above the CSC and then the time above the CSC are the determining parameters for efficacy (R = 0.69; F = 13.5; P = 0.001), whereas for amikacin and S. marcescens, the time above the CSC and then the area under the concentration time curve above the CSC predict efficacy (R = 0.74; F = 24.0; P = 0.0001). The lowest CSC is that of amikacin (about 8 mg/liter); those of gentamicin and tobramycin are about 15 mg/liter. In severe S. marcescens infections, intermittent amikacin dosing offers excellent bactericidal activity within the first 24 h. PMID- 1503437 TI - Metabolism of S-1108, a new oral cephem antibiotic, and metabolic profiles of its metabolites in humans. AB - The metabolism and pharmacokinetics of pivalic acid, a major metabolite of S 1108, were studied with three healthy volunteers. Concentrations of S-1006 (the active compound), pivalic acid, and pivaloylcarnitine in plasma and urine were measured after administration of S-1108. Recoveries in urine at the doses of S 1108 given (100 and 200 mg) were 33 to 41% for S-1006, 93% for total pivalic acid, and 89 to 94% for pivaloylcarnitine in 24 h, and maximum concentrations in plasma were 2 micrograms of S-1006 per ml, 1 micrograms of total pivalic acid per ml, and 2 micrograms of pivaloylcarnitine per ml after a 200-mg oral administration of S-1108. More than 90% of the pivalic acid was excreted as pivaloylcarnitine, and no measurable amount of free pivalic acid was present in urine samples, indicating that the pivalic acid liberated from S-1108 was almost quantitatively conjugated with carnitine in the human body. The level of free carnitine in plasma was unaffected by a single 200-mg administration of S-1108, whereas urinary excretion of free carnitine decreased as levels of acylcarnitine increased. The acylcarnitines were excreted primarily in the form of pivaloylcarnitine. This study clearly showed how the pivalic acid was metabolized and excreted in humans. The importance of monitoring carnitine, an essential cofactor in fatty acid metabolism, was also discussed in terms of its utilization by pivalic acid. PMID- 1503438 TI - Phase I clinical studies of S-1108: safety and pharmacokinetics in a multiple administration study with special emphasis on the influence on carnitine body stores. AB - S-1108, the prodrug of S-1006, was given to healthy volunteers three times a day (TID) for 8 days in a dose of 200 mg in a crossover placebo-controlled study. The safety of S-1108 and the pharmacokinetics of S-1006 and pivalic acid liberated from pivaloyloxymethyl ester of S-1108 were investigated. There were no abnormal symptoms or signs, as observed by physical and laboratory tests. The half-life and area under the concentration-time curve of S-1006 was reduced from 1.11 +/- 0.17 h at the first dose to 0.87 +/- 0.18 h at the last dose and from 7.30 +/- 1.10 to 5.20 +/- 0.85 micrograms.h/ml, respectively. However, there was no significant difference in the peak concentration between the two doses. Pivalic acid was found to be completely detoxified by conjugation with carnitine. The total urinary recovery of pivalic acid as pivaloylcarnitine was 98.7 +/- 3.6%, resulting in an increase of daily carnitine urinary excretion two- to threefold the predose value. During the multiple administration of S-1108, the plasma carnitine concentration was reduced to and maintained at 50 to 70% of the control value, suggesting that there might be enough carnitine store in the body to detoxify the pivalic acid in a dose of 200 mg TID. Moreover, the reduced plasma carnitine was rapidly returned to the control value within a few days after the cessation of the administration of 200 mg TID. PMID- 1503439 TI - Antimicrotubule benzimidazoles inhibit in vitro growth of Pneumocystis carinii. AB - Nine antimicrotubule benzimidazole derivatives tested in a Pneumocystis carinii culture system with human embryonic lung fibroblast monolayers inhibited organism proliferation. The concentrations of drugs inhibitory in culture ranged from 10 to 0.1 micrograms/ml, with thiabendazole being the least effective (10 micrograms/ml) and parbendazole being the most effective (0.1 microgram/ml). The parent compound, benzimidazole, was inactive at 10 micrograms/ml. Demonstration that this group of compounds has activity against P. carinii provides a new potential target that can be exploited, the microtubules. Also, the variability in the effectiveness of the compounds provides the basis for studies of structure activity relationships, which were initiated in this study. PMID- 1503440 TI - Overproduction of a penicillin-binding protein is not the only mechanism of penicillin resistance in Enterococcus faecium. AB - In 1989 and 1990, a large number of ampicillin-resistant strains of Enterococcus faecium were isolated from infected patients treated at intensive care units in Berlin, Germany. Twenty-five clinical isolates, including five different biotypes as classified by acid production from various sugars and a wide range of susceptibilities to ampicillin (MICs between 0.5 and 128 micrograms/ml), were selected for a detailed analysis of penicillin-binding proteins (PBPs). All strains contained a slowly reacting PBP with low penicillin affinity known to be present in enterococci. Overproduction of this PBP relative to susceptible isolates was noted, especially in all strains for which the MIC of ampicillin was 8 micrograms/ml, to a lesser degree in the more resistant strains, but not at all in the three highly resistant isolates for which the MIC was 128 micrograms/ml. In these three strains, this PBP appears to have a reduced affinity for beta lactams. The results suggest that overproduction of PBP 6 correlates only with intermediate resistance levels and that higher resistance is mediated by yet another, still unknown mechanism, probably including reduction of beta-lactam affinity in one or more PBPs. PMID- 1503441 TI - Interaction of Vibrio cholerae cells with beta-lactam antibiotics: emergence of resistant cells at a high frequency. AB - Unlike other gram-negative enteric bacteria, Vibrio cholerae cells were equally susceptible to penicillin and ampicillin and in general more susceptible than Escherichia coli to most of the beta-lactam antibiotics. The turbidity of penicillin-treated cultures contained to increase exponentially for about 3 h, although the cell viability declined rapidly within 30 min of penicillin addition. Prolonged treatment with beta-lactam antibiotics produced cells resistant to these antibiotics. A fluctuation test indicated that this resistance might be due to adaptive mutation. Cells resistant to a beta-lactam exhibited broad cross-resistance to other beta-lactam antibiotics. A new 12,000-Da outer membrane protein was detected both in beta-lactam-resistant cells and in wild type cells growing in medium containing beta-lactam antibiotics. While the penicillin-resistant cells had all of the penicillin-binding proteins (PBPs) present in the parental cells, significant differences in the relative proportion of low-molecular-weight PBPs were seen. The low-molecular-weight PBPs from resistant cells seemed to form more stable complexes with penicillin than those from the parental strain. PMID- 1503442 TI - Imipenem versus gentamicin combined with either cefuroxime or cephalothin as initial therapy for febrile neutropenic patients. AB - A prospective randomized study was conducted to determine the efficacy of imipenem-cilastatin (hereafter referred to as imipenem) (500 mg four times daily) versus combination therapy for febrile neutropenic patients receiving either no prophylaxis or ciprofloxacin for prevention of infections. Combination therapy consisted of gentamicin (80 mg every 8 h) plus either cefuroxime (1,500 mg every 8 h) or cephalothin (1,000 mg every 4 h) for suspected catheter-related infections. Ninety-four neutropenic fever episodes in 87 patients were evaluable for efficacy. The overall clinical rate of response to imipenem was significantly higher than that to combination therapy (91 versus 74%; P = 0.05). The difference in efficacy was most pronounced in patients with microbiologically documented infections (89 versus 53%; P = 0.025), which were predominantly caused by gram positive bacteria. Differences in susceptibility may have caused the better rate of response to imipenem. Two of 29 gram-positive bacteria were imipenem resistant, whereas 10 were resistant to cephalothin and cefuroxime and 12 were resistant to gentamicin. No causative gram-negative bacterium and 24 gram positive bacteria were isolated in 61 fever episodes with ciprofloxacin prophylaxis (oral). In contrast, nine causative gram-negative and five gram positive bacteria were isolated in 33 episodes without prophylaxis. The difference in distribution proved to be statistically significant for gram negative (P = 0.0001) as well as gram-positive (P = 0.025) bacteria, indicating that ciprofloxacin effectively prevented the occurrence of gram-negative bacteria and may have contributed to the relatively large number of gram-positive bacteria isolated. Empirical initial therapy with imipenem may be a valuable alternative to combination therapy for neutropenic fever episodes. PMID- 1503444 TI - Bactericidal activities of five quinolones for Escherichia coli strains with mutations in genes encoding the SOS response or cell division. AB - The bactericidal effects of five quinolones (at the optimum bactericidal concentration for strain AB1157) on 15 strains of Escherichia coli with mutations in genes for the SOS response or cell division was studied by a viable-count method. The kill rate data were normalized for growth rate and compared to those for the wild type, AB1157. Similar MICs of enoxacin and fleroxacin were obtained for all mutants; however, different mutants had differing susceptibilities to ciprofloxacin, norfloxacin, and nalidixic acid. Killing kinetic studies showed that mutants with constitutive RecA expression (recA730 and spr-55 mutants) survived longer than AB1157 with all quinolones. Mutants deficient in SOS induction, e.g., recA430 and lexA3 mutants, also survived longer, suggesting that induction of the SOS response by quinolones is harmful to wild-type cells. Recombination repair-deficient mutants (recB21, recC22, and recD1009 mutants) were killed more rapidly than AB1157, as were excision repair mutants, except with nalidixic acid. Mutants which were unable to filament (sfiA11 and sfiB114 mutants) survived longer than AB1157 with all agents, but a mutant defective in the Lon protease was killed more quickly. It was concluded that (i) recombination and excision repair were involved in the repair of quinolone-damaged DNA and (ii) continuous induction (in response to exposure to quinolones) of the SOS response, and hence induction of the cell division inhibitor SfiA, causes cell filamentation and thereby contributes to the bactericidal activity of quinolones. PMID- 1503443 TI - Comparisons of anti-human immunodeficiency virus activities, cellular transport, and plasma and intracellular pharmacokinetics of 3'-fluoro-3'-deoxythymidine and 3'-azido-3'-deoxythymidine. AB - 3'-Fluoro-3'-deoxythymidine (FLT), a candidate anti-AIDS compound in clinical trials, showed anti-human immunodeficiency virus type 1 (HIV-1) potency (50% effective concentration, 0.0052 microM) slightly better than or equal to that of 3'-azido-3'-deoxythymidine (AZT) in MT4 cells and was threefold more potent in H9 cells. There was no FLT resistance demonstrable in the AZT-resistant HIV-1 strains. Both FLT and AZT showed low cytotoxicity for MT4 cells, with selectivity indices (efficacy/toxicity ratio) of greater than 47,000 and greater than 33,000, respectively. Cellular permeation of FLT and thymidine (dThd) was greater than that of AZT, and FLT and dThd permeated the cell membranes by a carrier-mediated mechanism as well as by simple diffusion, as indicated by the existence of nitrobenzylthioinosine-5'-monophosphate-sensitive and -insensitive components. By contrast, transport of AZT into cells was by simple diffusion. The intracellular level of the triphosphate of FLT (FLTTP) in MT4 cells was two- to threefold higher than that of AZT (AZTTP) after exposure to 1.8 microM each compound for 12 h. The elimination kinetics of FLTTP and AZTTP in HIV-1-infected MT4 cells in fresh medium showed biphasic patterns, with initial half-lives of 1.03 and 1.09 h, respectively. In phytohemagglutinin-stimulated human peripheral blood lymphocytes, the FLTTP level was increased 59-fold compared with that in unstimulated cells at 12 h, was four- to sixfold higher than the level of AZTTP in stimulated cells at 12 h, and remained four- to fivefold higher during a 4-h elimination period in fresh medium and twofold higher at the end of a 12-h elimination period. Two- to eightfold more [3H]AZT than [3H]FLT was incorporated into the host cell DNA, and both [3H]AZT and [3H]FLT remained persistently incorporated for over 24 h. The incorporated [3H]AZT and [3H]FLT were alkali labile, whereas incorporated [3H]dThd was alkali stable. Pharmacokinetics of FLT in plasma of monkeys after intravenous (i.v.) administration showed that the FLT concentration in plasma declined, with a half-life of 1.19 +/- 0.1 h; the steady state volume of distribution was 0.93 +/- 0.2 liter/kg of body weight, and total clearance was 0.56 +/- 0.15 liter/kg. Oral bioavailability of FLT was excellent and comparable to i.v. bioavailability in terms of areas under the concentration time curves for three monkeys. Of the total dose, 41 to 61% was excreted in urine as unchanged FLT, and only 3.2 to 7.4% of the total dose was identified as glucuronide-conjugated FLT in urine 48 h after i.v. administration to monkeys. We conclude that FLT exhibits an anti-HIV-1 potency similar to that of AZT but with slightly better selectivity of effects and with higher intracellular active metabolite levels. PMID- 1503445 TI - The lipid A biosynthesis mutation lpxA2 of Escherichia coli results in drastic antibiotic supersusceptibility. AB - The conditionally lethal lpxA2 mutant of Escherichia coli, which lacks detectable UDP-N-acetylglucosamine acyltransferase activity and which produces greatly reduced amounts of lipid A after a shift to 42 degrees C (S. Galloway and C. R. H. Raetz, J. Biol. Chem. 265:6394-6402, 1990), was found to be, at conditions which promote normal growth, remarkably susceptible to a number of antibiotics. The MICs of hydrophobic antibiotics, such as rifampin, erythromycin, clindamycin, and fusidic acid, were 32- to greater than 128-fold lower for the lpxA2 strain than for the parent type strain, and those of the peptide antibiotics vancomycin and bacitracin were 32- and 256-fold lower, respectively. Futhermore, the lpxA2 strain was found to be sensitive to hypoosmotic conditions. Comparisons with the other characterized outer membrane permeability mutants, such as the heptose deficient strains of E. coli and Salmonella typhimurium, the acrA and abs mutants of E. coli, and the ssc-1 and class SS-B mutants of S. typhimurium, indicated that the lpxA2 mutant had characteristically the most antibiotic-supersusceptible phenotype. These findings advocate the possible use of the lpxA2 strain as a tool in various fields of basic and applied bacterial research in which the impermeability of the outer membrane currently poses problems. PMID- 1503446 TI - Effects of aluminum hydroxide and calcium carbonate antacids on the bioavailability of ciprofloxacin. AB - This study was designed to determine the effects of an aluminum hydroxide antacid and a calcium carbonate antacid on the bioavailability of ciprofloxacin (Cipro). Cipro (750 mg) was administered orally to 12 healthy volunteers in a three-way randomized crossover design. The three treatments included Cipro alone, four 850 mg calcium carbonate tablets taken 5 min before Cipro, and three 600-mg aluminum hydroxide tablets taken 5 min before Cipro. The relative bioavailability of Cipro when given with calcium carbonate was approximately 60% of the control value. When Cipro was given with aluminum hydroxide, the relative bioavailability was approximately 15%. Urinary recovery of Cipro in the aluminum hydroxide treatment group was approximately one-fourth of that in the calcium carbonate group. Although calcium carbonate decreased absorption to a lesser extent than aluminum hydroxide, these data suggest that antacids containing either aluminum or calcium should not be given concomitantly with Cipro. PMID- 1503448 TI - In vitro antistaphylococcal activity and testing of RP 59500, a new streptogramin, by two methods. AB - The in vitro antistaphylococcal activity of RP 59500, a new streptogramin, was comparable to those of vancomycin and teicoplanin against Staphylococcus aureus, and RP 59500 was the most active agent against coagulase-negative staphylococci. All staphylococcal strains were inhibited by 4 micrograms of RP 59500 per ml, including multiply resistant strains. Broth microdilution and agar dilution testing gave comparable results in 97% of the tests with RP 59500. PMID- 1503447 TI - Iron transport-mediated antibacterial activity of and development of resistance to hydroxamate and catechol siderophore-carbacephalosporin conjugates. AB - Peptides containing residues of N5-acetyl-N5-hydroxy-L-ornithine were evaluated as potential artificial siderophores of beta-lactam-hypersusceptible Escherichia coli X580. Only those peptides which were capable of forming a hexadentate complex around ferric iron, which is analogous to the natural siderophore ferrichrome, were able to reverse the growth inhibition effects of the ferric iron chelator ethylenediamine di(o-hydroxyphenylacetic acid). A synthetic bis(catechol) spermidine derivative, similar to the natural siderophores enterobactin and agrobactin, also exhibited siderophore activity with this strain. Conjugation of the N5-acetyl-N5-hydroxy-L-ornithine tripeptide and the bis(catechol) siderophore to the potent carbacephalosporin loracarbef and closely related analogs provided compounds which exhibited antibacterial activity against E. coli X580. As was observed with the naturally occurring albomycins, the initial bactericidal effect was followed by the appearance of survivors that were resistant to the test compound. An enhanced killing effect was observed when the parent was incubated simultaneously with hydroxamate and catechol siderophore antibiotic conjugates. Natural and synthetic siderophore growth promotion experiments with survivors resistant to the conjugates strongly suggested that disabled ferrichrome and enterobactin-catechol assimilation mechanisms may be responsible for the observed resistance. One isolated survivor was postulated to be a tonB mutant. The antibacterial activities of the described siderophore carbacephalosporin conjugates appear to be related to an iron transport assimilation mechanism and would not have been detected during routine MIC testing procedures. PMID- 1503449 TI - In vitro and in vivo antibacterial activities of levofloxacin (l-ofloxacin), an optically active ofloxacin. AB - The antibacterial activity of levofloxacin was compared with those of ofloxacin, ciprofloxacin, and other antibiotics. In general, levofloxacin was equally active or up to fourfold more active than ofloxacin against all 801 organisms tested. Levofloxacin was twofold [corrected] more active than ciprofloxacin against Streptococcus pneumoniae and 2- to 4-fold more active than ciprofloxacin against Staphylococcus aureus, Xanthomonas maltophilia, and Bacteroides fragilis. Levofloxacin was two- to eightfold more active than ciprofloxacin against coagulase-negative staphylococci and Acinetobacter spp., although these improvements in potency may not be clinically relevant. Levofloxacin inhibited 90% of streptococci when it was used at concentrations of 1 to 2 micrograms/ml. Levofloxacin was two- to fourfold less active than ciprofloxacin against most members of the family Enterobacteriaceae, such as Escherichia coli; Klebsiella pneumoniae; Citrobacter, Proteus, Providencia, Salmonella, and Yersinia spp.; and Pseudomonas aeruginosa. Both compounds were equally active against Pseudomonas cepacia. The in vitro DNA gyrase inhibitory activity of levofloxacin was as potent as that of ciprofloxacin, with a 50% inhibitory concentration of 0.65 micrograms/ml against an E. coli enzyme. In vivo, oral treatment with levofloxacin was as efficacious or more efficacious than that with ciprofloxacin in systemic as well as pyelonephritis infections in mice. Levofloxacin achieved higher concentrations in the serum and tissue of mice than did ciprofloxacin. This study presents some potential advantages of the pure L isomer of ofloxacin over ciprofloxacin and other quinolones. PMID- 1503450 TI - Evidence for in vivo incorporation of D-lactate into peptidoglycan precursors of vancomycin-resistant enterococci. AB - The VanA ligase encoded by the vancomycin resistance plasmid pIP816 of Enterococcus faecium BM4147 condenses D-alanine with various D-2-hydroxy and D-2 amino acids in vitro. D-Lactate added to the culture medium restored the vancomycin resistance of a strain that does not produce the VanH dehydrogenase and therefore appears to be a substrate of VanA in vivo. PMID- 1503451 TI - In vitro susceptibilities of Mycoplasma genitalium to antibiotics. AB - The susceptibilities of seven clinical isolates of Mycoplasma genitalium and three strains of Mycoplasma pneumoniae to a variety of antibiotics were examined by an agar dilution method. Macrolides, pristinamycin, and tetracyclines were very active against both species. Sparfloxacin was the most active quinolone tested. None of the 21 antibiotics tested had differential activity toward the two organisms. PMID- 1503452 TI - Tet determinants provide poor protection against some tetracyclines: further evidence for division of tetracyclines into two classes. AB - Atypical tetracyclines were active against Escherichia coli and Staphylococcus aureus strains containing determinants that mediate resistance to typical tetracyclines by efflux (Tet B and Tet K) or ribosomal protection (Tet M) mechanisms. The results support recently published data that tetracyclines are divisible into at least two classes on the basis of their modes of action. PMID- 1503453 TI - In vitro activity of Ro 23-9424, a dual-action antibacterial agent, against bacterial isolates from cancer patients compared with those of other agents. AB - The in vitro activity of Ro 23-9424 against bacterial isolates from patients with cancer was compared with those of fleroxacin, ciprofloxacin, cefoperazone, and ceftazidime. Ro 23-9424 inhibited the majority of the members of the family Enterobacteriaceae and all Aeromonas isolates at a concentration of less than or equal to 1.0 micrograms/ml. It was also active against Acinetobacter spp. and Haemophilus influenzae, including beta-lactamase-producing strains. The MIC for 90% of isolates (MIC90) of Pseudomonas aeruginosa was 16.0 micrograms/ml. All group A and B streptococci were inhibited by less than or equal to 0.25 micrograms/ml, and 90% of group G streptococci and Streptococcus pneumoniae were inhibited by 1.0 micrograms/ml. All methicillin-susceptible strains of Staphylococcus aureus and 60% of methicillin-resistant strains were susceptible to 2.0 micrograms of Ro 23-9424 per ml, whereas the MIC90 for Staphylococcus epidermidis and Staphylococcus hominis isolates was 4.0 micrograms/ml. Staphylococcus haemolyticus and Enterococcus spp. were less susceptible; MIC90s for them were 16.0 and 32.0 micrograms/ml. Ro 23-9424 has a broad antibacterial spectrum and potential utility for therapy of infections in cancer patients. PMID- 1503454 TI - A pneumococcal clinical isolate with high-level resistance to cefotaxime and ceftriaxone. AB - A beta-lactam-resistant serotype 23F Streptococcus pneumoniae clinical isolate from the cerebrospinal fluid of a pediatric patient from California is unusual in that the MICs of cefotaxime and ceftriaxone (2.5 micrograms/ml each) are higher than that of benzylpenicillin (0.3 micrograms/ml); the isolate also has patterns of penicillin-binding proteins and of cell wall peptides which are atypical compared with those of previously examined penicillin-resistant pneumococci. PMID- 1503455 TI - Kinetic interaction of biofilm cells of Staphylococcus aureus with cephalexin and tobramycin in a chemostat system. AB - Planktonic and young biofilm cells were completely eradicated after exposure of these cells to drug levels representing one loading and two maintenance doses of tobramycin and cephalexin. A very different picture was observed when antibiotic exposure was initiated on day 21. Complete eradication of the old biofilm cells was not observed even when the antibiotic exposure was continued for an extra 6 days. Regrowth of the organism was observed when the antibiotic exposure was terminated. PMID- 1503456 TI - In vitro studies of activities of some antifungal agents against Candida albicans ATCC 10231 by the turbidimetric method. AB - Different criteria (the drug concentration which inhibited 50% of growth [IC1/2], the lowest drug concentration at which growth was just less than 30% of that in a positive control well [IC30], the visual inhibitory concentration [ICv], and the minimum fungicidal concentration [MFC]) were applied to study the effects of some antifungal agents against Candida albicans. Amphotericin B, flucytosine, and bifonazole produced total growth inhibition. Clotrimazole, itraconazole, ketoconazole, and miconazole produced partial growth inhibition. The values of IC1/2 and IC30 were similar for all agents and avoided the problems of partial inhibition; the values of ICv and MFC were higher than those of IC1/2 and IC30. PMID- 1503457 TI - Effects of amino acids on expression of enterococcal vancomycin resistance. AB - The effects of various amino acids on vancomycin MICs obtained with resistant enterococci was investigated by using broth dilution testing. For both the type A (i.e., possessing transferable resistance to teicoplanin and vancomycin) and the type B (i.e., possessing teicoplanin susceptibility and nontransferable vancomycin resistance) resistant strains, vancomycin MICs in the presence of glycine were substantially lower than those in unsupplemented broth (range of MIC decrease, 8- to 128-fold). No such effect was seen with Enterococcus gallinarum AIB-39 or with the susceptible control Enterococcus faecalis ATCC 29212. Further testing of two type B strains (E. faecalis V583 and V583-2) showed that certain other amino acids (i.e., D-methionine, D-serine, D-alanine, and D-phenylalanine) had effects similar to that of glycine. Results of sodium dodecyl sulfate polyacrylamide gel electrophoresis with membrane preparations from these strains revealed the production of vancomycin-inducible proteins of sizes comparable to those describe for other enterococcal isolates that exhibit acquired vancomycin resistance. Even in the presence of 0.2 M glycine, the inducible proteins were produced. These results indicate that certain amino acids specifically interfere with the mechanism(s) of acquired vancomycin resistance in enterococci and that the nature of interference probably involves inhibition or circumvention of the inducible proteins' functions. PMID- 1503458 TI - Executive summary. Nursing's Agenda for Health Care Reform. PMID- 1503459 TI - This tuberculosis epidemic cannot be 'silent'. PMID- 1503460 TI - Responses to physician bonding editorial. PMID- 1503462 TI - Project teams developing models; defining perioperative practice, terminology. PMID- 1503461 TI - Responses to physician bonding editorial. PMID- 1503463 TI - New AIDS test licensed. PMID- 1503464 TI - Arthroscopic evaluation and treatment of rotator cuff pathology. A nursing perspective. PMID- 1503465 TI - Pressure ulcer development in the operating room. Nursing implications. PMID- 1503466 TI - Extracorporeal shock wave lithotripsy. The electromagnetic method. PMID- 1503467 TI - Gloving. Clinical question demands further research. PMID- 1503468 TI - Postoperative orthopedic autotransfusion. Successful management for the total knee arthroplasty patient. AB - Orthopedic autotransfusion is an effective technique that should be available to patients having total knee arthroplasty. Patient safety, however, must not be compromised simply because the blood is autologous. Blood products, in any form, require close observation and careful administration. The best results are achieved when the physician and all nursing departments involved have comprehensive knowledge of the system and the guidelines for its safe use. PMID- 1503469 TI - Autologous blood transfusion. Current trends, nursing implications. AB - Developing a quality perioperative autologous blood recovery program is a team effort. Members of transfusion committees, hospital blood bank personnel, OR staff members, and the members of the surgery committee are all possible sources of information. Your local blood center also may have literature or services that could be of assistance. Knowledge of current autologous transfusion alternatives will help nurses communicate with patients regarding transfusion therapy and will make nurses more valuable participants in the crucial decisions necessary to deliver optimal patient care in the perioperative period. PMID- 1503470 TI - Computerized nursing documentation systems. Development, implementation. PMID- 1503471 TI - Proposed recommended practices. Traffic patterns in the surgical suite. PMID- 1503472 TI - Proposed recommended practices. Monitoring the patient receiving i.v. conscious sedation. PMID- 1503473 TI - Creative strategies for retaining OR nurse recruits. PMID- 1503474 TI - Issues and legislation surrounding trauma care. PMID- 1503475 TI - The doctrine of res ipsa loquitur places burden on perioperative personnel. PMID- 1503477 TI - [Endoscopic therapy of cancer]. PMID- 1503478 TI - [Endoscopic treatment of esophageal cancer]. AB - With the advance of endoscopic equipment the number of superficial cases of esophageal cancer has been increasing dramatically. It has been clarified as to which cancer can be treated as an early cancer with desirable results as in gastric cases. Endoscopic treatment for early cancer already established in gastric or colorectal cases have been applied to esophageal cases with nationwide popularity. Especially endoscopic mucosal resection, which can assure accurate pathological findings, can be the treatment of choice for endoscopic procedures for early cancer. In this paper, our methodology of endoscopic treatment of early esophageal cancer is introduced and our endoscopic approach to advanced cases which is still to be established is reported. PMID- 1503476 TI - [The need for death education]. AB - "Death Education" is at the same time "Life Education." For many years I have endeavored to create an awareness of the need for death education in Japan. In this paper I would like to stress the necessity of death education for the following three groups. 1. For medical personnel. Three objectives of death education: 1) Learn to understand the fears and anxieties of the patients facing death and try to reduce their excessive fears and anxieties. 2) Familiarize yourself with the ethical issues related to terminal care and try to establish a warm relationship based on trust and continue communication with the dying patient till the end. 2. For patients. 1) Be aware that the time of your life is limited and try to discover the preciousness of the remaining time. Meditate on the uniqueness of your own death. 2) Finish your unfinished business, reevaluate your human relationships and benefit from a life review therapy. 3) Remove the taboo on death, arrange your own funeral and consider the possibility of another life after death. 3. For the patient's family and friends. 1) Continue warm communication with the dying patient till the end. 2) Prepare for your own bereavement and grief. 3) Try to make your own grief process an opportunity for personal growth. When a cure is no longer possible for a dying patient, the focus of our endeavors should be loving care of the person. Death education can help us to provide better terminal care during the final stage of life. PMID- 1503479 TI - [Endoscopic treatment of lung cancer]. AB - There are many kinds of endoscopic treatment for lung cancer. In this paper the authors describe these methods and present representative cases. The first is laser treatment. There are three methods of endoscopic laser treatment. One is vaporization using high-power lasers, for example, the Nd-YAG laser. Indications for high-power laser treatment include obstructive lesions of the trachea or large bronchi with no recognizable peripheral focus. The second is photodynamic therapy (PDT) using tumor-specific photosensitizers, and low-power lasers. PDT has potential for the treatment of early stage lung cancer. The third is "laser chemotherapy," which is a new method developed by the authors using low-power lasers, e.g., He-Ne lasers, combined with chemotherapy. It is possible that antitumor drugs could be administered in doses lower than used at present. The second method is bronchofiberscopic ethanol injection therapy for stenosis or obstruction of central airways in order to obtain airway dilatation or hemostasis. The third method is brachytherapy or endobronchial radiation for central type lung cancer. We use a bronchofiberscope to place the applicator into the target bronchial lumen. Radiation therapy is performed with 60Co high dose rate endobronchial radiation by a remote after-loading system. The value of laser treatment has been amply demonstrated and the other methods are also yielding encouraging results in the treatment of lung cancer. PMID- 1503480 TI - [Endoscopic treatment of early gastric cancer]. AB - We assessed the results of endoscopic resection (ER) of early gastric cancer using electrocoagulation with high frequency current. Resection was performed utilizing endoscopic double-snare polypectomy (EDSP) and electrocoagulation. The initial endoscopic total resection rate was 65.0% (119/183 lesions). There were 32 lesions in which no residual cancer was present at follow-up biopsy or surgery, and when these were included the endoscopic resection cure rate was 82.5%. Extensive tissue necrosis and degeneration occurred in the resected stump as a result of using electrocoagulation. Since an increase in suitable patients and an expansion of the indications for endoscopic resection are anticipated in the future, careful clinical evaluation of endoscopic resection based on the results of pathological assessment of the resected tissue is needed. PMID- 1503481 TI - [Endoscopic treatment of early colorectal cancer]. AB - Early cancer of the colon and rectum is currently treated by endoscopic or surgical resection. We studied the indications for endoscopic treatment of early colorectal cancers (80 lesions) in relation to the size and macroscopic findings. The endoscopic treatment consists of polypectomy for a pedunculated or a sessile polyp and strip biopsy for a plaque-like or a depressive lesion. Microscopic or most small cancers were completely treated endoscopically. From macroscopic findings of the early cancers, type Ip (less than 2cm and 2cm in diameter) was completely treated by polypectomy, type I s and type II a (less than 1cm and 1cm in diameter) by polypectomy or strip biopsy, and type II c (less than 0.5cm and 0.5cm in diameter) by strip biopsy. PMID- 1503482 TI - [Phase III study of DWA2114R for ovarian cancer]. AB - A phase III study of DWA2114R for ovarian cancer was carried out in CAP regimen by a cooperative study group consisting of 42 institutions. The response rate of 31 cases for DWA2114R regimen was 38.7% and out of 30 cases for CDDP regimen 46.7%. No significant differences were observed between the two regimens in efficacy, adverse reactions, and abnormalities in laboratory findings except for red blood cell and creatinine clearance, but the incidence of thrombocytopenia was likely to be lower in DWA2114R than in CDDP regimen. Since the DWA2114R regimen did not need hydration, or require diuretics, DWA2114R is more useful in the treatment of ovarian cancer than cisplatin. PMID- 1503483 TI - [Prospective randomized trial comparing modified FAM (5-fluorouracil (5-FU) + adriamycin + mitomycin C) versus 5-FU alone for the treatment of non-resectable pancreatic and biliary tract carcinomas (the 1st trial in non-resectable patients). Study Group of Surgical Adjuvant Therapy for Carcinomas of the Pancreas and Biliary Tract]. AB - The modified FAM (5-fluorouracil (5-FU) + adriamycin (ADR) + mitomycin C (MMC)) therapy (FAM group) was compared with 5-FU mono-therapy (F group) by multi institutional randomized trial in the patients with cancer of the pancreas or the biliary tract who underwent non-resection. The patients in FAM group received 6 mg/m2 of i.v. MMC during operation, 310 mg/m2 of i.v. 5-FU for 5 days in the 1st and 3rd postoperative weeks and 12 mg/m2 of i.v. ADR in the 2nd postoperative week. Those in F group received only 5-FU course in the administration schedule of FAM group. Among the cases which completed respective whole administration schedules. 35 cases in FAM group and 36 in F group, better effect than partial response (PR) was observed in neither groups, and there was no significant difference between groups with respect to overall/each disease survival duration, progression-suppressed duration and clinical effect. Primary adverse effects were alimentary symptoms and hepatic dysfunction, neither of which was serious, and there was no difference between groups except that hair loss was observed in more cases in FAM group (p less than 0.05). Results in FAM group did not statistically surpass those in F group, but a tendency was observed that FAM group was better than F group in terms of survival duration and clinical effect for cancer of the gall-bladder. PMID- 1503484 TI - [Evaluation of 58 patients with acute leukemia]. AB - We made a retrospective study of 44 patients with acute non-lymphocytic leukemia (ANLL) and 14 patients with acute lymphocytic leukemia (ALL) admitted to our hospital from September 1984 to May 1991. The complete remission (CR) rate of ANLL was 90.9%, against 85.7% for ALL. The 5-year survival of ANLL was 50.7%, and that of ANLL under age 60 years was 70.3%. The 2-year median survival of ALL was 35.1%. These results were obtained with response-oriented individualized therapy, and intensive chemotherapy with a view to eradication of residual leukemic cells. Eight elderly patients with ANLL were treated with cytosine arabinoside in low doses. Complete remission was achieved in 6 patients, but these cases relapsed. These treatments should be reconsidered for long CR duration. Our schedules of response-oriented individualized therapy were too flexible to apply at another institute so they should be arranged for general application. PMID- 1503485 TI - [Intensive induction chemotherapy of adult acute myelogenous leukemia by continuing daunorubicin, behenoyl-cytosine arabinoside, 6-mercaptopurine and prednisolone until marrow aplasia]. AB - Intensive induction chemotherapy was applied to 25 patients with acute myelogenous leukemia by continuing drugs (daunorubicin, behenoyl-cytosine arabinoside, 6-mercaptopurine and prednisolone) until the achievement of severe bone marrow aplasia (leukemic cells less than 1,000/microliters). Complete remission (CR) was achieved in 18 (72%). Numbers of partial remission and an early death were 5 (20%) and 2 (8%), respectively. Although median nadirs of white blood cells (WBC) and platelet counts (Pl) (205/microliters and 8,200/microliters, respectively) were remarkably low, recovery of WBC (over 1,000/microliters) and Pl (over 50,000/microliters) were achieved in 23.8 and 24.5 days, after an initiation of the chemotherapy. Sepsis was a most frequently observed complication during induction stage and a duration of fever was 2-48 days (median 15). Median duration of CR was 22.9 months. Unexpectedly, 11 of 17 CR (except one with bone marrow transplanted) relapsed after 4.2-41.4 months (median; 9.4), but 6 (35.3%) still remain in first CR for 30.5-72.9 months (median; 51.4). A long-term survival might be obtained by intensifying induction chemotherapy in about one fourth of patients, but the intensification or application of non-cross resistant anti-leukemic agents in post-remission therapy may be required to avoid relapses even if induction is intensified. PMID- 1503486 TI - [Comparative study of cefpiramide + amikacin versus piperacillin + amikacin in granulocytopenic patients: a randomized, prospective study]. AB - Cefpiramide + amikacin (CPM + AMK) was compared in a prospective randomized trial with our standard regimen of piperacillin plus amikacin (PIPC + AMK) as an empiric therapy for fever in 252 episodes of 141 patients with granulocytopenia. Initial profound granulocytopenia (fewer than 100/mm3 mature granulocytes) was present in approximately 69% of the patient trials in both treatment groups. Both groups were equally distributed in regard to age, disease, pretreatment WBC count and duration of antibiotic treatment, although septic shock was more frequently seen in CPM + AMK. Responses to PIPC + AMK and CPM + AMK were similar for microbiologically and clinically documented infection, while the response rate for clinically documented infections treated with PIPC + AMK was superior to CPM + AMK (63% vs. 52%). Patients with persistent granulocytopenia of less than 100/mm3 of mature granulocytes without a rise during therapy responded significantly less in both groups (22% vs. 9%) than those in whom the granulocyte count rose (79% vs. 79%). Toxicities of jaundice or disordered hepatic function test were infrequent in both groups. Disordered renal function test occurred in one case in PIPC + AMK groups. PMID- 1503487 TI - [Effects of UFT and loxiglumide (CR1505) on liver metastasis of human pancreatic cancer cell line, KP-1 N in nude mice]. AB - Effects of caerulein (CCK), 5-FU and CCK antagonist, loxiglumide (CR1505), were studied on the growth of human pancreatic cancer cell line, KP-1 N, in vitro. And effects of UFT and CR 1505 were also studied on liver metastasis in nude mice. The growth of KP-1 N was stimulated approximately 40% by addition of 10(-10) M of CCK in vitro. CR1505 antagonized the action of CCK, that is, the 40% growth rate increase was suppressed by addition of 25 microM of CR1505. Moreover, the growth rate of the cells dose-dependently decreased by the addition of CR1505. 5-FU also dose-dependently inhibited the growth of KP-1 N in culture. 5-FU additionally decreased the growth rate of KP-1 N in combination with CR1505. A number of metastatic nodules were found in the liver of nude mice a month after injections of KP-1 N cells into the spleen CR1505 suppressed the liver metastasis in nude mice which were administered with UFT. These results suggest that CR1505 would be useful for the treatment of human pancreatic cancer in combination with UFT. PMID- 1503488 TI - [Ototoxicity of cis-diammine glycolato platinum, 254-S]. AB - Ototoxicity of cis-diammine glycolato platinum, 254-S, was evaluated from the results obtained in phase II studies for head & neck cancer, lung cancer, breast cancer, gastrointestinal cancer, urogenital cancer and gynecological cancer at 114 institutions, and in randomized comparative study of 254-S plus vindesine vs. cisplatin plus vindesine for advanced non-small cell lung cancer conducted at 41 institutions. In these studies, 254-S was administered at doses ranging from 80 to 100 mg/m2, repeated at least 2 times at 4-week intervals. Impaired hearing was examined in a hearing audiometry test before and after 254-S administration. The incidence of impaired hearing was 25.8% (16/62) in the 254-S phase II studies. The incidences in the randomized comparative study were 17.6% (3/17) for the 254 S/vindesine group and 20.0% (3/15) for the cisplatin/vindesine group. From these results, the ototoxicity of 254-S was thought to be similar to that of cisplatin in incidence and type. PMID- 1503489 TI - [A case of advanced breast cancer effectively treated with tamoxifen]. AB - A 69-year-old female with advanced breast cancer was daily administered 20 mg of tamoxifen. After 4 months, her left breast tumor decreased in size. Left breast tumor and metastatic lymph nodes disappeared completely (CR) 7 months later. CR has been continued for 6 months up to the present, and the patient has been enjoying favorable quality of life. PMID- 1503490 TI - [A bladder cancer with complete remission after arterial infusion of anti-cancer agents (CDDP and THP) and balloon-catheter occlusion of the internal iliac artery: a case report]. AB - The case was a 63-year-old male with the chief complaint of hematuria. A local doctor made the diagnosis of a bladder tumor (egg-sized) on the basis of the results of ultrasonography. CT-scan and cystoscopy. He was thus referred to our Department for treatment. Histopathological study of the biopsied tumor specimen revealed that the tumor was a squamous cell carcinoma. The bilateral internal iliac arteries were occluded for 48 hours, and 100 mg of CDDP and 40 mg of THP were arterially infused. After 7 days, hematuria disappeared, as did the tumor 5 weeks after treatment. No malignancy was noted from histological examination of a biopsy specimen obtained from the cured cancer region using a cystoscope. Since then, there was no recurrence for 12 months. Thus, this approach is thought to be an effective treatment for primary bladder cancer. PMID- 1503491 TI - [Suppression of breast cancer cells by cardiac glycosides]. PMID- 1503492 TI - [Psychological evaluation in chemotherapy of lung cancer]. PMID- 1503493 TI - [Cell culture and its application primary culture of human hepatocytes and its application]. AB - Difficulty in obtaining human liver specimens has made a delay in the development of methodology for isolation and primary culture of human hepatocytes compared to animal hepatocyte cultures. Recently the collagenase-liver-perfusion technique, which was developed for rat hepatocyte isolation, has been applied to prepare isolated human hepatocytes. This method greatly improved the yield and viability of hepatocytes of human liver tissues. Since then, the isolated human hepatocytes and their primary culture have been widely used for studies of hepatic metabolism, regeneration, transplantation, hepatitis B virus infection, hepatotoxins, detection of human carcinogens, hepatocarcinogenesis and so forth. These current studies were reviewed. PMID- 1503495 TI - Delayed type hypersensitivity is abnormal in patients with lichen planus. AB - Lichen planus is characterized by the histological features of a cell-mediated attack on the epidermis. To see whether there is any defect in cutaneous immunity in non-lesional skin, we measured the response to a contact sensitizer in 17 patients with lichen planus and 27 control subjects. Sensitization was induced with 30 micrograms dinitrochlorobenzene applied to the thigh. The subjects were challenged 4 weeks later with three doses of dinitrochlorobenzene (8.8, 12.5 and 17.7 micrograms), and responses were quantified with calipers as the change in skinfold thickness at 48 h. Patients with lichen planus were significantly less responsive with smaller reactions at all challenge doses. These abnormalities suggest that the skin is abnormal in areas unaffected by the rash, and raise the possibility that there may be a primary defect in the cutaneous immune system in lichen planus. PMID- 1503494 TI - Isolation of human skin-derived lymph: flow and output of cells following sodium lauryl sulphate-induced contact dermatitis. AB - By means of microsurgery a peripheral subcutaneous lymph vessel draining a defined skin area was isolated and cannulated on the lower leg of six healthy volunteers. Lymph was collected over a period of 8 days. During the first 2 days baseline values for lymph flow and output of cells were established. A contact dermatitis was then induced in the drained skin area by the application of 10% sodium lauryl sulphate. All six probands developed a mild to moderate irritant contact dermatitis. Lymph flow as well as output of cells increased with the intensity of the skin reaction. Subsequent local treatment with clobetasol propionate decreased the cell output, but the lymph flow increased further. Neither lymph flow nor output of cells returned to the initial baseline values at the end of the study, when the clinical signs of contact dermatitis had completely disappeared. During the experiment significant individual variations were found, with means ranging from 0.10 to 0.48 ml/h for lymph flow and from 8700 to 174000/h for cells, which probably depended mainly on the different topographies and calibres of the cannulated lymph vessels. PMID- 1503496 TI - Thermal and sweating responses in normal and atopic subjects under internal and moderate external heat stress. AB - To compare the thermoregulatory responses of normal subjects and patients with atopic dermatitis, the effect of exercise under moderate heat stress was examined in two groups of subjects. Each group of eight subjects (controls or clinical atopics) underwent a 90-min experiment after being equipped with probes for measurement of core and skin temperatures, heart rate and overall and local sweating rates. Sweat surface tension was determined from sweat collection made at the end of the session. The experimental procedure was as follows: 30 min rest at thermoneutrality, 30 min cycling at 90 W at 36 degrees C, followed by 30 min recovery sitting at rest at 36 degrees C on the cycloergometer. None of the registered variables differed significantly between the normal and atopic subjects except for variations in mean skin temperature, core-to-skin temperature difference and sweat surface tension. Since local sweating on non-affected skin under a controlled thermal clamp was not altered by atopy, it can be concluded that the thermoregulatory modifications under heat stress is of vasomotor origin, the benefit of which, in terms of heat dissipation capacity, remains uncertain. There may be alterations in the constituents of sweat, but not in its excretion rate. Local, rather than central, factors are probably involved in this qualitative change, which remains to be investigated. PMID- 1503499 TI - Organ culture of psoriatic skin: effect of TGF-alpha and TGF-beta on epidermal structure in vitro. AB - Normal skin and uninvolved and involved psoriatic skin specimens were maintained in vitro in organ culture. The 3-4 mm punch-biopsied skin specimens were put freely into the culture medium with or without fetal calf serum, under an atmosphere of 95% O2 plus 5% CO2, and rotated at 60 rpm at 37 degrees C. In the serum-free culture medium (vitamin A-free) granular layers appeared in the involved psoriatic epidermis in culture. Addition of TGF-alpha caused normal skin and uninvolved and involved psoriatic skin specimens to become acanthotic and to degenerate easily almost to the full thickness of the epidermal layer in proportion to increasing concentrations of TGF-alpha as well as with the duration of the culture, but without disappearance of their granular layers. TGF-beta caused the normal skin and uninvolved psoriatic skin specimens to become thinned without disappearance of granular layers, but caused the involved psoriatic skin specimens to be thinned without appearance of granular layers in serum-containing medium or with their disappearance in the serum-free medium. TGF-beta also antagonized the acanthotic and degenerative effect of TGF-alpha. The results suggest that TGF-alpha and TGF-beta may partially be related to the induction of psoriatic epidermal lesions. PMID- 1503498 TI - Carbonic anhydrase--a marker for fenestrated capillaries in psoriasis. AB - A strong correlation between capillary fenestrations and the demonstration of carbonic anhydrase (CA) has previously been shown. In the present histochemical study we sought to determine whether CA could serve as a marker for fenestrated capillaries in psoriasis. In normal human skin capillary staining for CA was found only in the fenestrated capillaries of the perifollicular and periglandular plexus. In psoriatic skin lesions, however, the intrapapillary capillaries also reacted for CA. From ultrastructural investigations it is known that these capillaries are fenestrated. Our findings have shown that there is a strong correlation between fenestrated and CA-positive capillaries in normal human skin as well as in the lesional skin of psoriatics. Therefore, the demonstration of CA activity may serve as a specific and sensitive marker for fenestrated capillaries in psoriasis using an uncomplicated method, which makes it possible to detect numerous fenestrated capillaries in a single histological section. PMID- 1503497 TI - The interleukin-2 receptor in lesions and serum of bullous pemphigoid. AB - The interleukin-2 receptor (IL-2R) is mainly expressed on activated T cells. Depending on its rate of synthesis, a portion is released from the cell surface as soluble IL-2R (sIL-2R). Since the role of mononuclear cells in the pathology of bullous pemphigoid (BP) is not well understood, we determined the sIL-2R in both blister fluid and serum of 15 BP patients with generalized disease before initiating systemic treatment. In addition, we obtained both lesional and perilesional skin biopsies and examined the mononuclear infiltrate with a panel of monoclonal antibodies. In BP blisters, sIL-2R levels were significantly increased (2070 +/- 350 U/ml), (+/- SEM) compared with serum samples taken at the time of blister puncture (1340 +/- 290 U/ml). In six patients with blisters due to second-degree burns or friction and in five suction blister volunteers, sIL-2R levels were normal in both blisters and serum. In BP, elevated serum levels decreased to normal during therapy, correlating with disease activity. The immunohistology showed that 30% of mononuclear cells in the dermal infiltrate of lesional skin expressed the IL-2R, whereas only 15% were positive in perilesional skin. IL-2R-positive cells are the most likely source of the shed receptor in BP blisters. Our results indicate the presence of activated T cells in lesions and peripheral blood of BP and thus underline the importance of cell-mediated immune mechanisms in the pathology of this disease. PMID- 1503500 TI - Immunohistological and immunoelectron microscopic identification of TNF alpha in normal human and murine epidermis. AB - The presence, distribution and cellular localization of tumour necrosis factor alpha (TNF alpha) were investigated in normal human and murine epidermis using immunohistological and immunoelectron microscopic methods with monoclonal and polyclonal antibodies. The immunostaining revealed an intercellular plasma membrane and cytoplasmic labelling of the epidermal keratinocytes, but no labelling of Langerhans cells, melanocytes and Merkel cells. Large amounts of TNF alpha were regularly found in the sebaceous glands. These findings demonstrate that epidermal keratinocytes and especially sebocytes produce and release TNF alpha and that this keratinocyte-derived cytokine may be important for the structural and functional homeostasis of normal epidermis. PMID- 1503501 TI - Expression of cadherin cell adhesion molecules during human skin development: morphogenesis of epidermis, hair follicles and eccrine sweat ducts. AB - Expression of E (epithelia) and P (placental) cadherin cell adhesion molecules was examined immunohistochemically using human developing skin. In adult skin, E cadherin was expressed on cell surfaces of whole epidermal layers including skin appendages, whereas P-cadherin was expressed only on those of basal layers and the outer layers of skin appendages, which was consistent with the compartment of proliferating cells. In fetal skin, while the patterns of E- and P-cadherin expression were generally similar to those in the adult, P-cadherin temporarily showed a unique spatiotemporal expression pattern in developing sweat ducts. During this stage, the expression of P-cadherin accumulated in the epidermal ridges and showed a discrepancy with the compartment of proliferating cells. These results suggest that the expression of P-cadherin is spatiotemporally controlled, and may be closely related to the segregation of basal layers as well as to the arrangement of epidermal cells into eccrine sweat ducts, but is not closely related to cell proliferation. PMID- 1503502 TI - MON-150, a versatile monoclonal antibody against involucrin: characterization and applications. AB - A monoclonal antibody, designated MON-150, was found serendipitously to react strongly with the granular layer of normal human epidermis and with the upper spinous layers of psoriatic epidermis. From analysis by flow cytometry of cultured human keratinocytes, it appeared that the percentage of MON-150-positive cells strongly increased when the cells reached confluence and the growth fraction declined. To identify the antigen recognized by MON-150, a lysate of human keratinocytes was subjected to affinity chromatography using a MON-150 Sepharose column. This yielded a single protein of approximately 350 kDa as measured on Superose 6 FPLC gel permeation chromatography using non-denaturing conditions. In Western blot analysis under denaturing and reducing conditions, a 140-kDa protein was detected. The subcellular localization and the molecular weight of the antigen recognized by MON-150 suggested that the antigen involved might be involucrin. This was confirmed using a commercial polyclonal antiserum against involucrin. We conclude that MON-150 is a new, versatile antibody against human involucrin. PMID- 1503503 TI - Effect of cyclosporins A, G, and H on normal and ichthyotic keratinocyte growth in culture. AB - Cyclosporin A (CsA) was first used in organ transplantation and for the treatment of autoimmune disorders because of its strong immunosuppressant properties. Several laboratory studies have demonstrated that CsA exerts an inhibitory action on the growth of various cell types in culture, including human skin cells. Such an influence on epidermal keratinocytes, if not associated with the serious adverse effects of CsA medication, would be of interest for the treatment of hyperproliferative genodermatoses such as non-bullous congenital ichthyotic erythroderma (NBCIE). In our study, we used cyclosporin G (CsG) and H (CsH), analogues CsA, to examine the impact of these three cyclosporins on normal and ichthyotic keratinocyte growth in vitro. Epidermal cells were grown in a low calcium, serum-free medium in the presence or absence of cyclosporins A, G or H (1-10 micrograms/ml). The effects of a 72-h exposure to the drugs were evaluated by cell counting, 3H-thymidine incorporation and cytofluorimetric analysis of the BrdU-labelled cell suspensions. Our findings indicate a dose-dependent keratinocyte growth inhibition by the three cyclosporins. The data obtained with the three quantitation methods were in agreement and the cyclosporin-mediated effects were observed in both normal and ichthyotic keratinocyte cultures. CsG and CsH proved less effective than CsA, which induced a highly significant reduction even at 1 microgram/ml. Our results suggest, however, that ichthyotic keratinocytes are more sensitive to CsG and H when compared with normal cells (50% inhibition of 3H-thymidine uptake at significantly lower doses). A possible therapeutic action of non-toxic doses of CsG and CsH on NBCIE and other hyperproliferative epidermal diseases needs to be confirmed clinically. PMID- 1503504 TI - The antipsoriatic drug, anthralin, inhibits protein kinase C--implications for its mechanism of action. AB - In psoriatic patients, anthralin is known to attenuate lesional inflammation, but often generates perilesional dermatitis. This phenomenon is well reflected by the contrasting action of anthralin on human leukocytes. The release of reactive oxygen species (ROS) is inhibited by anthralin in phorbol ester-activated leukocytes, whereas anthralin directly induces this cellular response in unstimulated cells. In order to elaborate further the underlying mechanisms, we compared the kinetics of anthralin and different well-characterized stimuli, including the phorbol ester, phorbol-12-myristate-13-acetate, in this test system. Compared with standard stimuli, anthralin only marginally induced the release of ROS from human leukocytes and displayed different kinetics. Protein kinase C (PKC), the major cellular phorbol ester receptor, is considered to be involved in the regulation of this cellular response. Furthermore, its involvement in the pathophysiology of psoriasis has been suggested. Therefore, we also investigated the effects of anthralin on purified PKC. Anthralin was found to inhibit the enzyme activity in a dose-dependent manner but not to display any stimulatory effects. The present results provide first evidence that the therapeutic activity of anthralin, at least in part, might be mediated by inhibition of PKC. PMID- 1503505 TI - UV-induced DNA strand breaks detected by in situ nick translation in human epidermis. PMID- 1503506 TI - The long term follow-up of asymptomatic women with Chlamydia trachomatis. AB - A community oriented intervention program was initiated in 1985 in 12 rural communities in southern Israel to identify and treat women of reproductive age with markers of Chlamydia trachomatis (CT) infection. Among 860 women tested, 21 (2.4%) had CT IgG antibody titers greater than or equal to 128, or CT IgA antibody titers greater than or equal to 16, and 9 of these women had positive cultures for CT. The 21 women, as well as their male partners, received specific anti-CT treatment, and were followed up for 5 years to assess obstetric complications, and to evaluate the effectiveness of treatment. In 9 women positive cultures became negative. In 13 out of the 17 cases with sequential follow-up a four fold decrease in IgG specific antibody titers was observed. Yet, in all but two of the cases, IgA specific antibody titers remained greater than or equal to 16. PMID- 1503507 TI - Lactic dehydrogenase activity of platelet subpopulations during pregnancy. AB - We determined the LDH activity of different platelet subpopulations throughout pregnancy. While no changes in LDH content occurred in large, dense platelets, a significant change was found in small, light platelets. PMID- 1503508 TI - Creatine phosphokinase isoenzyme activity in umbilical artery, umbilical vein and capillary blood of newborn infants at term. AB - Serum levels of creatine phosphokinase isoenzyme pattern (CPK MM, MB, BB) were measured in cord blood and capillary blood samples of 20 healthy term infants. Total CPK activity was high but similar in all samples, the main source being derived from the CPK-MM fraction. The CPK-MB fraction was absent in cord blood. Moreover, CPK-BB activity was significantly higher in capillary blood than in cord blood. These results suggest specific organ involvement in the production of CPK fractions. PMID- 1503509 TI - The effect of periconceptional multivitamin-mineral supplementation on vertigo, nausea and vomiting in the first trimester of pregnancy. PMID- 1503510 TI - Dihydroergotamine causes fetal growth retardation in guinea pigs. AB - Dihydroergotamine is a vasoactive drug which enhances venous tone, central blood volume and cardiac output but has variable effects on arterial tone. Its effect on the uterine arterial circulation is unstudied and yet dihydroergotamine is widely used to treat postural hypotension in pregnant and nonpregnant women. For this reason we undertook studies to determine if its chronic use had any adverse effect on the placental arterial circulation and fetal growth in an animal model. We administered dihydroergotamine (14 micrograms/kg/day) to pregnant guinea pigs with 2-4 fetuses from day 30-60 of pregnancy. At term under light ketamine anaesthesia, we measured maternal arterial blood pressure and blood flow to myometrium, placenta, skin and skeletal muscle using left ventricular injection and standard sampling techniques. Vascular resistance was calculated from arterial blood pressure and blood flow. When controlled for litter size, both fetal weight and the fetal weight/placental weight ratio were significantly less (P less than 0.001) in the dihydroergotamine group (-21% and -11% respectively). Placental blood flow was decreased by 51% (P less than 0.01) whereas myometrial blood flow, skin blood flow and muscle blood flow were not significantly altered. There was no significant difference in mean arterial blood pressure but placental vascular resistance was increased (+45%, P less than 0.05) while it was unchanged in myometrium and skin and decreased in skeletal muscle (-51%, P less than 0.05). Chronic administration of dihydroergotamine at a clinical dosage level has a constrictive effect on the placental vasculature of guinea pigs with a subsequent adverse effect on flow and fetal growth. PMID- 1503512 TI - Vaginal schwannoma. AB - In the patient reported here, a solid tumor lying between the vagina and the rectum was detected using various imaging techniques (ultrasonography and MRI), and S100 protein was found in the tumor cells. Thus, a schwannoma was the final diagnosis. This is a slow-growing neoplasm, and its early detection is difficult. PMID- 1503511 TI - Non-ovarian peritoneal papillary serous carcinoma with high CA125 levels. AB - A patient with peritoneal papillary serous carcinoma involving the colon and omentum is presented. Following palliative right-sided hemicolectomy and partial omentectomy, chemotherapy was given. The patient had a second look operation after 6 months when a pelvic clearance was done and histology revealed some residual tumor in one mesosalpinx. She was well and clinically free of recurrence after a further 6 months. Serum CA125 and CEA levels were measured and CA125 levels remained high throughout. PMID- 1503513 TI - Antenatal diagnosis of prune belly syndrome. PMID- 1503514 TI - Magnetic resonance imaging of uterine leiomyosarcoma. AB - The magnetic resonance imaging (MRI) findings in a patient with uterine leiomyosarcoma are reported. MRI provides higher contrast resolution in soft tissues than ultrasonography or CT, and the MRI findings described in this case report suggest that MRI can be used to help differentiate between leiomyosarcoma from myoma. PMID- 1503515 TI - Multiple systems organ failure. PMID- 1503517 TI - Acute small bowel volvulus in adults. A sporadic form of strangulating intestinal obstruction. AB - Small bowel volvulus is an uncommon but important cause of small intestinal obstruction. It often results in ischemia or even infarction. Delay in diagnosis and surgical intervention increases morbidity and mortality rates. Based on cause, small bowel volvulus can be divided into primary and secondary type. Goals for treatment of small bowel volvulus should include physician awareness of this uncommon diagnosis, accurate workup, and advanced surgical intervention. The presentation and subsequent management of 35 patients with small bowel volvulus confirmed by laparotomy are reviewed and discussed. The incidence of small bowel volvulus in the adult European and North American is low. The resultant mortality rate, however, makes diagnosis critically important. The cardinal presenting symptom is abdominal pain. There is no single specific diagnostic clinical sign or abnormality in laboratory or radiologic finding. In practice, the diagnosis can only be made by laparotomy. The failure to perform an exploratory laparotomy cannot be justified. Early diagnosis and early surgery are the keys for successful management of strangulation obstruction of the small bowel. PMID- 1503518 TI - Saline resuscitation after fixed-volume hemorrhage. Role of resuscitation volume and rate of infusion. AB - The authors have reported previously that small-volume resuscitation (1.8 x bled volume) with 0.9% NaCl restores blood volume and attenuates hormonal responses after large hemorrhage without correction of arterial hypotension. The authors studied the role of rate of infusion in this observation in chronically prepared dogs (aortic flow probe, right atrial pressure and volume, and arterial catheters) after 30% hemorrhage (24.1 +/- 0.4 mL/kg). After 30 minutes, subjects were observed either without treatment (no resuscitation) or with infusion of 43 mL/kg 0.9% NaCl over 3 hours by one of three protocols: (1) impulse infusion over 10 minutes, (2) variable rate infusion, bolus with tapering infusion, or (3) constant rate infusion. Significant improvement in cardiac output and in blood volume and significant decreases of vasopressin and arterial catecholamines were observed in all fluid-treated groups. This benefit was relatively independent of rate of infusion, although impulse infusion produced greater early improvement, which dissipated with time, and constant rate infusion produced better late results. In none of the fluid-treated groups were these improvements reflected in improved mean arterial pressure compared with the no resuscitation group. The authors conclude that small-volume, slow-rate saline infusion produces physiologic benefits that cannot be assessed by easily measured clinical parameters. Thus, early resuscitation after trauma could aid patients even if arterial pressure is unchanged. This benefit might be even greater in patients with uncontrolled bleeding because arterial pressure, and hence bleeding, may not be increased by resuscitation of this type. A reassessment of the value of prehospital fluid resuscitation in the injured patient is warranted. PMID- 1503516 TI - Multiple organ failure. Pathophysiology and potential future therapy. AB - Multiple organ failure (MOF) has reached epidemic proportions in most intensive care units and is fast becoming the most common cause of death in the surgical intensive care unit. Furthermore, in spite of the development of successive generations of new and more powerful antibiotics and increasing sophisticated techniques of organ support, our ability to salvage patients once MOF has become established has not appreciably improved over the last two decades. Clearly, new therapeutic strategies aimed at preventing or limiting the development of the physiologic abnormalities that induce organ failure are needed to improve survival in these critically ill patients. Based on our rapidly increasing knowledge of the mechanisms of MOF and the fruits of molecular biology, a number of new therapeutic approaches are in various stages of development. To effectively use these new therapeutic options as they become available, it is necessary to have a clear understanding of the pathophysiology of MOF. Thus, the goals of this review are to integrate the vast amount of new information on the basic biology of MOF and to focus special attention on the potential therapeutic consequences of these recent advances in our understanding of this complex and perplexing syndrome. PMID- 1503519 TI - Biosynthetic human growth hormone preserves both muscle protein synthesis and the decrease in muscle-free glutamine, and improves whole-body nitrogen economy after operation. AB - As a reproducible human trauma model, patients (n = 17) undergoing elective cholecystectomy were studied for 3 postoperative days. They were randomly allocated to receive either recombinant human growth hormone (hGH; 0.3 U/kg/24 hours) or placebo together with total parenteral nutrition, including 0.2 gN/kg/24 hours and 135 kJ/kg/24 hours. Before operation and on the third postoperative day, percutaneous muscle biopsies were performed to determine the concentration and size distribution of ribosomes and the free amino acid concentrations. The significant postoperative decrease in the total ribosome concentration (15.3 +/- 6.4%) and the polyribosome concentration (20.9 +/- 6.5%) in the control group was impeded in the group receiving synthetic hGH. Muscle free glutamine decreased by 35.6 +/- 4.2% in the control group and to a lesser extent in the group that was given hGH after operation (p less than 0.05). The protein content of skeletal muscle was unchanged. The cumulated nitrogen balance for the study period was negative in the control group (-7.09 +/- 0.71 gN), but was not different from zero in the hGH group (-2.32 +/- 1.66 gN). It is concluded that synthetic hGH administered after operation has beneficial effects on the whole-body nitrogen economy, as indicated by the unchanged capacity for protein synthesis in skeletal muscle, the preserved levels of muscle free glutamine, and improvement in the whole-body nitrogen balance. The effects of hGH on skeletal muscle protein and amino acid metabolism can explain the postoperative nitrogen sparing effect attributed to hGH. PMID- 1503520 TI - Preoperative and long-term cardiac risk assessment. Predictive value of 23 clinical descriptors, 7 multivariate scoring systems, and quantitative dipyridamole imaging in 360 patients. AB - A total of 360 patients underwent preoperative cardiac risk assessment using 23 clinical parameters, seven multivariate clinical scoring systems, and quantitative dipyridamole-thallium imaging to predict postoperative and long-term myocardial infarction and cardiac death after noncardiac surgery. There were 30 postoperative and an additional 13 cumulative long-term cardiac events after an average follow-up of 15 months. Clinical descriptors were not useful in predicting the outcome of individual patients. The postoperative and long-term cardiac event rates were 1% and 3.5%, respectively, in patients with normal scans or fixed perfusion defects, and 17.5% and 22% in patients with reversible defects. Using quantitative indices reflecting the amount of jeopardized myocardium, patients could be stratified by dipyridamole imaging into multiple scintigraphic subsets, with corresponding postoperative and 1-year coronary morbidity and mortality rates ranging from 0.5% to 100% (p = 0.0001). Thus, postoperative and long-term cardiac events cannot be predicted clinically, whereas quantitative dipyridamole imaging accurately identifies high-risk patients who require preoperative coronary angiography. PMID- 1503521 TI - Selected sperm differ from nonselected cells in their electrophoretic mobility (EPM) after demembranation. AB - Human semen samples were first treated by swim-up migration or by Percoll density gradient centrifugation for selection of spermatozoa. The net surface charges of spermatozoa in the resulting compartments were indirectly evaluated by the electrophoretic mobility (EPM) during spermatozoal microelectrophoresis. Significantly different electrophoretic mobilities were measured between the compartments after demembranation with 0.1% (v/v) Triton X-100. However, without intermediate treatment by the detergent no significant differences were detected between the spermatozoal EPM. In addition, spermatozoa were divided into migrated and nonmigrated spermatozoal populations by the swim-up technique, and then treated with urea to remove spermatozoal coats. No significant differences in EPM were detected between these two groups. This investigation demonstrates that selected spermatozoa from semen exhibit an additional dimension of superiority, in EPM, to nonselected spermatozoa, which may better equip them for the process of fertilization. Measurements of EPM, therefore, may provide yet another, perhaps valid, means of developing a clinical tool for evaluating the potential fertilizing capacity of a semen sample in infertility studies. PMID- 1503523 TI - A double method sperm wash for artificial insemination. AB - Recently, there have been concerns regarding the presence of reactive oxygen species (ROS) produced during sperm processing for insemination. However, the sperm wash methods that yielded low ROS levels also had low sperm recovery after processing. The objective of this study was to compare sperm recovery after swim up from pellet, overlay, and 2-layer Percoll wash methods with the recovery after the double method wash. The latter method consisted of a combination of 2 sperm wash methods, namely, the overlay and the Percoll method. Motile sperm were first collected through the overlay method. The leftover semen was then processed through the 2-layer Percoll method to scavenge motile sperm and the resultant pellet combined with the pellet from the overlay method. In this manner, the level of ROS was kept to a minimal, sperm recovery was improved, and a mixture of sperm with different surface properties was produced as a result of using different processing methods. The results indicated an improvement in sperm recovery and in total sperm motility in noncryopreserved sperm after using the double method wash when compared with the other wash methods. The study suggests that the double method wash is a feasible method for processing sperm for insemination. PMID- 1503522 TI - Effect of spermine on sperm capacitation of guinea pig in vitro. AB - Spermine (Sp) 10(-5) mM had vigorous activity of guinea pig spermatozoa, while it completely abolished sperm forward motility (SFM) at a concentration of 10(-3) mM. There appeared to be a dose relationship to inhibition to motility. 2 Difluoromethylornithine 10 mM antagonized the Sp-induced inhibition of SFM after 3 h of incubation. Capacitation of a guinea pig sperm was inhibited by Sp in a concentration-dependent manner. The majority of acrosome-reacted sperm did not display hyperactivated motility. Precapacitated sperm were able to undergo the acrosome reaction (AR) in the presence of Sp. Moreover, Sp-mediated inhibition of capacitation was a reversible process. Once sperm capacitation was completed, Sp no longer inhibited AR. Before capacitation, the content of Sp in spermatozoa was 4.5 +/- 0.5 micrograms/5 x 10(7) cells, whereas in case of capacitated spermatozoa it was significantly decreased (2.1 +/- 0.4 micrograms/5 x 10(7) cells). The penetration of spermatozoa into the zona-free hamster eggs in the presence of Sp was markedly decreased, but it did not affect the fertilizability of ova as compared to the control. These results suggest that Sp may be an inhibitory agent of sperm capacitation in guinea pig in vitro, and it may also be involved in the modulation of capacitation. PMID- 1503524 TI - Diet-induced changes in the male reproductive system of rats. AB - Either quantitative or qualitative modification of diet interferes markedly with the reproductive functions of the rat. The effect of chick mash or cowpeas (Vigna unquiculata) on body growth, accessory sex organ weights, serum testosterone, and epididymal histology was studied. Body growth was markedly decreased in cowpeas fed group. Binucleated, multinucleated giant cells (MGCs), and lymphocytes were found in large numbers in the lumen of caput and cauda epididymis of the cowpea fed group. No noticeable effect was seen in chick mash-fed group. Serum testosterone levels were significantly decreased in cowpea-fed group. Presence of MGCs in cowpea-fed animals indicates epididymal dysfunction and probably renders them infertile. PMID- 1503525 TI - Testicular injury: late results of semen analyses after uniorchiectomy. AB - Semen parameters from 4 patients with testicular injury after uniorchiectomy were investigated. Semen volume and sperm morphology were not affected after the operation, but sperm count and motility were severely diminished. Two of 4 cases showed azoospermia, and the other 2 cases showed low values in both sperm count and motility. After 150-300 days from the operation, 2 cases recovered to the normal range in sperm count while the other 2 remained in the abnormal range. In sperm motility, 3 cases recovered to the normal range but the rest remained abnormal. The results suggest that long-term follow-up in semen parameters is needed when unilateral orchiectomy is performed. PMID- 1503526 TI - Glutathione therapy for male infertility. AB - Eleven infertile men were treated with glutathione (600 mg/day IM) for 2 months. The patients were suffering from dyspermia associated with various andrological pathologies. Standard semen and computer analyses of sperm motility were carried out before treatment and after 30 and 60 days of therapy. Glutathione exerted significant effect on sperm motility patterns. Glutathione appears to have a therapeutic effect on some andrological pathologies causing male infertility. PMID- 1503527 TI - Adverse effects of chronic GnRH antagonist administration on seminiferous epithelium in adult rats. AB - Seminiferous epithelium in adult rats was studied by light and electron microscopy after 5 weeks of chronic administration of GnRH antagonist (Ac-D2 Nal 1, D4ClPhe 2, DTrp 3, DArg 6, DAla 10; GnRH code-103-289-10, National Institutes of Health, USA). In these rats, the epithelium showed significant accumulation of vacuoles in more than 80% of the tubules, along with germ cell degeneration and nuclear pyknosis. Disruption in the process of spermatogenesis was also very much evident. In most of the tubules studied (greater than 90%), germ cell development was arrested beyond the pachytene spermatocyte stages. The vacuoles in the seminiferous epithelium were different sizes and when magnified were seen to consist of a thickened outer margin of solid nonfibrous coat within the Sertoli cell cytoplasm. Associated changes in the interstitium showed increased intertubular space but no inflammatory type of response. In actual cell counts, the decrease in the average number of macrophages was 32% and in Leydig cells 23%, while the total number of all types of cells in the interstitium was 30% less than that of the controls. Following the treatment, weights of testis, epididymis, seminal vesicle, and ventral prostate were drastically reduced. Rats treated with testosterone supplementation (60 micrograms/rat day) to GnRH antagonist recovered testicular and epididymal weights to approximately 57% and seminal vesicle and ventral prostate weights by 82.9 and 84%, respectively. Normalcy returned to the tubular epithelium and the interstitial cell counts were restored to original levels. PMID- 1503528 TI - Epidermal growth factor contents in seminal plasma as a marker of prostatic function. AB - Epidermal growth factor (EGF), first identified in extracts from submaxillary salivary glands of adult male mice, acts as a potent mitogen in a wide variety of cells and tissues in culture. Human EGF, a polypeptide of 53 amino acids isolated from human urine, has been identified in several biological fluids, including prostatic fluid and seminal plasma. Epidermal growth factor content in seminal plasma was measured by RIA. The EGF content in seminal fluid did not change after bilateral vasectomy and the first fraction of sample obtained by split ejaculation contained a significantly larger amount of EGF than the second fraction. Seminal EGF originates from the prostate. There was a close correlation between EGF and zinc contents in seminal fluid. The seminal fluid EGF content was lowered in patients with prostatitis and systemic androgen deficiency. The EGF content in seminal fluid seems to be a reliable indicator of prostatic function. PMID- 1503529 TI - Effects of human antisperm antibodies on development of preimplantation embryos. AB - The effects of antisperm antibodies (ASAs) present in sera of immunoinfertile patients and vasectomized men were investigated on preimplantation embryonic development in mice. Of the nine immunoinfertile sera tested, two were effective in inhibiting blastulation rates of in vitro cultured murine 2-cell embryos (p less than .05 to .002). Similarly, sera from two of the three vasectomized men were capable of affecting early embryonic development in mice (p less than .05 to .002). Specificities of the embryotoxic effects of ASAs were further confirmed by culturing embryos in the presence of affinity-purified monovalent Fab' antibodies isolated from these sera. Fab' antibodies from only one of the two immunoinfertile patients whose sera affected blastulation rates, and from one of the three vasectomized men were effective in influencing blastulation rates of in vitro cultured 2-cell murine embryos (p less than .05 to .001), mainly due to an arrest of development at 2 to 8-cell and morula stages. In the Western blot procedure, none of the immunoinfertile Fab' antibodies recognized any specific band on blots of extracts from murine ova or 2-cell embryos. However, all the immunoinfertile Fab', but not fertile control Fab', specifically recognized a protein band in the M(r) 25 +/- 2 kD region, on the Western blots of extract from murine blastocyst stage embryos. In addition, Fab' from one immunoinfertile serum, which inhibited embryonic development, reacted specifically with a protein band in the lower molecular range (approximate M(r) 12 kD) on Western blot involving exact from blastocysts. Fab' antibodies of sera from vasectomized men did not react with any specific protein band on blots of extracts from murine ova, 2-cell embryo, or blastocyst. These results suggest that ASAs from some immunoinfertile patients and vasectomized men, especially those reacting with 12 kD blastocyst protein, are capable of affecting preimplantation embryonic development in mice, and thus may contribute toward immunologically medicated infertility both at fertilization and postfertilization stages. PMID- 1503530 TI - Relatedness of the flagellins from methanogens. AB - Purified flagellar filaments isolated from six methanogens were composed of multiple flagellins. Two flagellins were present in Methanococcus deltae (Mr = 34,000 and 32,000), Methanoculleus marisnigri (Mr = 31,000 and 25,500) and Methanococcus jannaschii (Mr = 31,000 and 27,500), three in Methanothermus fervidus (Mr = 34,000, 25,000 and 24,000) and four or more in both Methanococcus vannielii and Methanococcus maripaludis (Mr ranging from 27,500 to 32,000). The flagellins of M. fervidus and M. deltae reacted positively with glycoprotein specific stains. The flagellins of M. deltae, M. maripaludis and M. vannielii were closely related to those of M. voltae based on cross-reactivity with antisera raised against M. voltae flagellins and homology with flagellin-specific oligonucleotide probes to the N-terminus and leader peptide of M. voltae flagellins. Similarities appear to exist among the flagellins of M. fervidus, M. marisnigri and Halobacterium halobium based on cross-reactivity with antisera produced against the flagella of Methanospirillum hungatei JF1. The N-termini of the flagellins from the mesophilic Methanococcus spp. and M. marisnigri show homology with the N-termini of other archaebacterial flagellins. These N-termini may undergo a modification involving removal of a leader peptide. PMID- 1503532 TI - Purification and properties of a F420-nonreactive, membrane-bound hydrogenase from Methanosarcina strain Go1. AB - The distribution of the F420-reactive and F420-nonreactive hydrogenases from the methylotrophic Methanosarcina strain Go1 indicated a membrane association of the F420-nonreactive enzyme. The membrane-bound F420-nonreactive hydrogenase was purified 42-fold to electrophoretic homogeneity with a yield of 26.7%. The enzyme had a specific activity of 359 mumol H2 oxidized.min-1.mg protein-1. The purification procedure involved dispersion of the membrane fraction with the detergent Chaps followed by anion exchange, hydrophobic and hydroxylapatite chromatography. The aerobically prepared enzyme had to be reactivated anaerobically. Maximal activity was observed at 80 degrees C. The molecular mass as determined by native gel electrophoresis and gel filtration was 77,000 and 79,000, respectively. SDS gel electrophoresis revealed two polypeptides with molecular masses of 60,000 and 40,000 indicating a 1:1 stoichiometry. The purified enzyme contained 13.3 mol S2-, 15.1 mol Fe and 0.8 mol Ni/mol enzyme. Flavins were not detected. The amino acid sequence of the N-termini of the subunits showed a higher degree of homology to eubacterial uptake-hydrogenases than to F420-dependent hydrogenases from other methanogenic bacteria. The physiological function of the F420-nonreactive hydrogenase from Methanosarcina strain Gol is discussed. PMID- 1503531 TI - Nickel-dependent reconstitution of hydrogenase apoprotein in Bradyrhizobium japonicum Hupc mutants and direct evidence for a nickel metabolism locus involved in nickel incorporation into the enzyme. AB - A double mutant (JH103K10) was created from hydrogenase constitutive mutant (JH103) by replacement of a chromosomal 0.60 kb nickel metabolism related locus with a kanamycin resistance gene. The double mutant required 10 to 20 times more nickel (Ni) to achieve near parental strain levels of hydrogenase activity. In the absence of nickel, both JH103K10 and JH103 synthesized high levels of (inactive) hydrogenase apoprotein (large subunit, 65 kDa). With nickel, the double mutant JH103K10 synthesized the same level of hydrogenase apoenzyme (65 kDa subunit) as the JH103 parent strain; however, whole cell hydrogenase activity in JH103K10 was less than half of that in JH103, and the CPM (due to 63Ni in hydrogenase) of membranes and the calculated ratio of nickel per unit of hydrogenase enzyme of the double mutant were 40% of that in JH103. Therefore, the difference in hydrogenase activities between the double mutant and the Hupc strain can be accounted for by different abilities of the strains to incorporate nickel into the hydrogenase apoenzyme. The addition of nickel ions to previously Ni-starved and then chloramphenicol-treated Bradyrhizobium japonicum whole cells (JH103 and JH103K10) resulted in (an in vivo) restoration of hydrogenase activity, suggesting that the apoprotein synthesized in the Ni-free cultures could be activated by addition of nickel even in the absence of protein synthesis. The extent of reconstitution of active hydrogenase by nickel was greater in the absence of chloramphenicol. Hydrogenase apoprotein could not be activated by nickel in vitro even with the addition of ATP. The successful in vivo but not in vitro results suggest that enzymatic but cell-disruption labile factors are required for Ni incorporation into hydrogenase. PMID- 1503533 TI - Accuracy in diagnosis of ectopic pregnancy by transvaginal ultrasonography. AB - Forty patients suspected to have ectopic pregnancy by transvaginal ultrasonography had surgery. 77.5% were confirmed to have ectopic pregnancy and 10% had other abnormal pelvic findings. The transvaginal approach appears to enable us to diagnose ectopic pregnancy at an earlier date, with the earliest diagnosis made at 4 weeks 0 days of amenorrhoea. In cases of confirmed ectopic pregnancy, the presence of a complex adnexal mass was the most common feature seen on transvaginal ultrasound and its predictability of ectopic pregnancy is enhanced by a concomitant finding of an empty uterus (95%) or free fluid in the Pouch of Douglas (94%) in the presence of a positive hCG test. The significance of transvaginal ultrasound features, and the advantages of transvaginal over transabdominal ultrasound, are discussed. PMID- 1503534 TI - Sonographic evaluation of clinical suspicion for ectopic pregnancy. AB - Analysis of transabdominal ultrasonic findings of 167 patients presented with clinical suspicion of extrauterine pregnancies (EUP), all with measurable serum HCG, has been undertaken. Patients were divided into two main groups, namely those with demonstrable typical intrauterine gestational sac (46.7%), and those without (53.3%). This later group of patients, i.e., without intrauterine sac, was further subdivided into four other groups depending on whether or not they have adnexal mass and/or fluid in cul-de-sac. In this first subgroup of patients (21 cases), without any demonstrable mass or fluid, a positive predictive value (PPV) for EUP of only 28.6% was obtained. With ultrasound showing fluid but no mass, the PPV was 55.6%, while those with both mass and fluid, the PPV as high as 95.7% was possible. Characterization of the adnexal mass or cul-de-sac findings among those with empty uterus may further improve PPV. The results of this study indicates that ultrasonic examination can help to provide a more correct diagnosis in the investigation of EUP. EUP can be easily excluded, in the great majority of cases, with sonographic visualization of intrauterine pregnancy. In the case of empty uterus with no mass or fluid, patients should be closely followed up with HCG titer and ultrasonic examination. For those with empty uterus with fluid, culdocentesis may be indicated; whereas in the case of empty uterus with mass, laparoscopy should be considered as additional investigative procedures. PMID- 1503535 TI - Sheehan's syndrome following eclampsia: a case report. AB - A case of Sheehan's syndrome following eclampsia is presented. The clinical features were not recognised early probably because the condition was not suspected, being a rare sequel of eclampsia. Non availability of specialist care may have been partly responsible and is highlighted. Increased awareness of all possible aetiological factors in this condition is necessary for clinicians. PMID- 1503536 TI - Prenatal diagnosis of holoprosencephaly by transvaginal ultrasonography in the first trimester. AB - A diamniotic-monochorionic pregnancy of twins was revealed by transvaginal ultrasonography: one fetus with holoprosencephaly was diagnosed at 11 weeks of gestation. This is the first case of holoprosencephaly diagnosed in the first trimester. Prenatal diagnosis of this anomaly in the first trimester is now possible by transvaginal ultrasonography. PMID- 1503537 TI - Clinical course of early fetal loss and its chromosomal characteristics. AB - The relationship between types of chromosomal abnormalities and fetal development documented by ultrasonography was discussed in early spontaneous abortions. The subjects were 113 patients who had vaginal ultrasonography at least twice between 6 and 8 weeks of pregnancy, among 167 abortuses with chromosome analyzed. The results were also compared against those for 303 normally developing fetuses. The results obtained in the present study suggested that each fetus with a chromosomal abnormality succumbed at or after a specific stage of fetal development and that the fetal death might be the results of severe fetal growth suppression. PMID- 1503538 TI - The Israel perinatal census. AB - A nation-wide perinatal census which included 22,815 deliveries was carried out. The cesarean section rate was 9.6% and the perinatal mortality rate was 13.5/1000. Using a logistic regression analysis the risk factors for cesarean section and for perinatal mortality were ranked. Breech presentation and one uterine scar were found to be the most important risk factors for cesarean section and breech presentation, maternal disease and multiple pregnancy for perinatal mortality. Low birth weight rate was 6.9% with nonsignificant differences between the various ethnic groups. The national cesarean section rate in breech presentation was 57.8%. It was performed mainly at the extremes of birth weight. From those with one previous cesarean section 55.1% delivered vaginally and 44.9% abdominally. The chance for vaginal delivery is higher (67.2%) providing the woman had delivered vaginally in the past. Comparison between primiparae and multiparae showed that preeclampsia, hypertension and diabetes mellitus were all significantly more frequent among older parturients and among primiparae. PMID- 1503539 TI - Elastase activity of endocervical mucus in normal pregnancy. AB - Elastase activity of 294 samples of endocervical mucus taken from 125 normal pregnant women during the visits to antenatal clinic were measured. Activity of the enzyme increased gradually with the advance of gestational age. Steep rising of the enzyme was seen between 34-35 weeks of gestation and the peak was achieved at 37 week since then the enzyme activity sustained at relatively high level until deliveries. Average activity of the enzyme after 34 weeks of gestation showed significant difference over that of earlier period. To use delivery date as a referent point, the peak was reached in the last fourth week of pregnancies and then sustained until deliveries. Significantly higher average activity was also seen in these last 4 weeks of gestation. These correlated very well to the fact that cervical maturation progresses most rapidly during last month of pregnancy. Immunohistochemical staining for elastase demonstrated elastase containing granules in polymorphonuclear leukocytes. These cells found in cervical tissue taken from immediately postpartal women were much more than in those of early pregnant women. These findings may be the evidences support roles of granulocyte elastase in the process of cervical maturation preceding spontaneous labors in normal pregnancies. PMID- 1503540 TI - The immunohistochemical localization of new membrane-associated placental tissue proteins (MP2 A, B, C, D, and E) in human and cynomolgus monkey placentae. AB - New membrane-associated placental tissue proteins (MP2 A, B, C, D, and E) were investigated by avidin-biotin immunoperoxidase technique in the human and cynomolgus monkey placentae, decidua and umbilical cords. In human early placentae, MP2 A, B, C, and E were localized mainly in the membrane of villous syncytiotrophoblasts and cytotrophoblasts. Histiocytes in the villous stroma were positive for MP2 A, B, D, and E. In human term placentae, obvious positive staining for MP2 A, B, C, and E was observed in the membrane of villous syncytiotrophoblasts, in the amniotic epithelium, and in the umbilical cord sheath. Histiocytes in the villous stroma were positive for MP2 A, B, C, E, and especially for MP2 D. Importantly, MP2 A, C, and E were positive in polymorphonuclear neutrophils, since most of these common antigens are also carcinoma-associated, suggesting clinical usage of MP2 proteins as a new tumor marker. In the cynomolgus monkey placentae, similar immuno-staining results were obtained. The monkey can thus serve as a experimental model for the investigation of the placental proteins. PMID- 1503541 TI - Cell-mediated immunity in cervical intraepithelial neoplasia. AB - Various immune parameters, i.e., peripheral T and B cell distribution, T cell subpopulation, interleukin 2 (IL-2) activity and in vitro lymphocyte responses to phytohemagglutinin (PHA) and concanavalin A (Con A), were investigated in 24 pretreated patients with cervical intraepithelial neoplasia (CIN) and in 35 normal controls. Of the measured parameters, lymphocyte response to PHA was significantly lower in the CIN than control group (P less than 0.05). The values of all other measured parameters were similar in both groups. PMID- 1503542 TI - The effect of nifedipine and dipyridamole on the Doppler blood flow waveforms of umbilical and uterine arteries in hypertensive pregnant women. AB - In a study of 45 hypertensive pregnant women, the systolic velocity/diastolic velocity ratio and pulsatility index of the umbilical and uterine arteries showed good correlation with the maternal blood pressure, and they appeared to provide a good parameter for the fetoplacental condition. Using the pulse Doppler method, we studied the effects of the antihypertensive agent nifedipine and of dipyridamole (an agent used to treat proteinuria) on the blood flow of the umbilical and uterine arteries in 16 hypertensive pregnant women. The results proved that both drugs caused a decrease in the vascular resistance of the umbilical artery and suggested that they increased the blood flow volume of this artery and were useful in the treatment of hypertension during pregnancy. PMID- 1503543 TI - Malakoplakia of the omentum and endometrium. AB - A rare case of malakoplakia involving the omentum and endometrium is presented. This is the first documented case of malakoplakia in the Thai population. PMID- 1503544 TI - Experience with screening for abnormal glucose tolerance in pregnancy: maternal and perinatal outcome. AB - In order to determine the prevalence of glucose intolerance in pregnancy, 2,230 consecutive women attending the antenatal clinic at the Aga Khan University Medical Centre in Karachi, Pakistan were subjected on the first antenatal visit, irrespective of gestational age, to a 75 g glucose challenge followed 2 hr later by plasma glucose determination. The test, was repeated at 28-32 weeks of gestation for those patients who had an abnormal initial screen at less than 28 weeks gestation followed by a normal glucose tolerance test and for those who had a risk factor for gestational diabetes even though the initial screen at less than 28 weeks gestation was normal. The initial glucose challenge test was abnormal (2 hr plasma glucose greater than 140 mg%) in 8.6% of the screened population. An oral glucose tolerance test on these patients revealed a prevalence for the entire population of 3.5% of gestational diabetes and 1.9% of impaired glucose tolerance test based on the modified O'Sullivan criteria. Patients with abnormal glucose tolerance test were older, had higher parity, a past history of macrosomia and a family history of diabetes compared to the controls. These patients also had a higher incidence of preterm labour and caesarean section. In the neonates hypoglycemia and hyperbilirubinemia were similarly higher. The fetal abnormality rate was 5.6% and the perinatal mortality was 28/1,000 which were higher than the controls. PMID- 1503545 TI - Analysis of relative mRNA levels and protein patterns in brains of rat strains bred for differing levels of emotionality. AB - mRNA and protein populations were studied in the brains of Maudsley reactive (MR) and Maudsley nonreactive (MNR) rat strains, which exhibit differing levels of emotionality. Translational analysis of forebrain mRNA indicated that the relative levels of two translation products (42 kDA, pI 5.0; 30 kDa, pI 5.8) were increased in the MR compared to the MNR strain. In addition, a charge-shift variant of a 36 kDa protein was present in the MR strain. Analysis of brain protein patterns indicated that a protein of 39 kDa, pI 5.0, was found to be more abundant in MR compared with MNR strains in both frontal cortex and hippocampus and the relative level of one protein (40 kDa, pI 5.8) was decreased in the frontal cortex. PMID- 1503546 TI - The hyperactive spontaneously hypertensive rat learns to sit still, but not to stop bursts of responses with short interresponse times. AB - The spontaneously hypertensive rat (SHR) is hyperactive and has been proposed as an animal model of attention-deficit hyperactivity disorder (ADHD). Although ADHD in most cases is treated with central stimulants, behavior therapy has also been used, but with relatively limited success. The purpose of the present study was to investigate suppression of SHR hyperactivity by differentially reinforcing immobility (DRI) using a positive reinforcer. The DRI schedule required that the rat remain immobile in a particular part of an operant chamber, the target, in order to obtain the reinforcer. The time requirement, the DRI value, of these periods was increased progressively. The results showed that time spent on the target increased by increasing DRI value in both hyperactive and control rats. However, the total number of movements, on as well as outside the target, was higher for the hyperactive rats. The behavior grouped into two independent response components. One component consisted of immobility responses with durations less than 1 s, actually bursts of active responses; the other component consisted of immobility responses with durations more or less matching the DRI requirement. The reinforcement schedule modified the long-lasting immobility component in both groups. SHR received more reinforcers than WKY as long as the schedule did not require too long periods of immobility. However, the total number of movements on target was not reduced in SHR; on the contrary, it increased somewhat as the schedule requirements increased. If the behavior of ADHD children consists of two, or more, independent components similar to the ones observed in the present study, the present results may offer an explanation of why behavior therapy has limited success in the treatment of ADHD. PMID- 1503547 TI - Are paw preference differences in HI and LO mice the result of specific genes or of heterosis and fluctuating asymmetry? AB - Collins (1985) has described two separate mouse strains, obtained by selective breeding, which differ in having high (HI) or low (LO) degrees of paw preference on a standard test. In this paper I argue that the differences between these strains may not be due to a specific gene (or genes) but, instead, probably reflect differences in the total heterozygosity of the strains, such that the HI strain is more heterotic than the LO strain. Greater degrees of heterozygosity are argued to buffer against fluctuating asymmetry and hence result in a greater degree of paw preference. PMID- 1503548 TI - A biometrical genetic approach to chromosome analysis in Drosophila: detection of epistatic interactions in geotaxis. AB - Chromosome analysis has been widely used as a first step in elucidating the genetic architecture of several behaviors of Drosophila melanogaster. These chromosome studies have generally used incomplete designs or fairly simple statistical analyses. Here I reanalyze two data sets on geotaxis from Pyle (1978) and Ksander (1966) using a biometrical genetic design. Results from the biometrical genetic reanalysis suggest that individual differences in geotaxis might be due to genes on all three major chromosomes which show extensive epistatic interactions. PMID- 1503549 TI - Male sexual signaling is defective in mutants of the apterous gene of Drosophila melanogaster. AB - The apterous (ap) gene of Drosophila melanogaster exhibits extreme pleiotrophy: its functioning is essential for life, normal wing structure, juvenile hormone production, female fertility, and normal development of female sexual receptivity. Four mutant ap alleles (ap4, ap56f, apc, and apblt) were characterized for three additional phenotypes: male mating success, courtship behavior, and immature male sex appeal (the ability of males to stimulate homosexual courtship). Mating success with mature wild-type virgin females is reduced in males mutant for the ap gene, the extreme case being ap4/ap4 males, which are behaviorally sterile. In ap mutants, nonwing courtship elements are qualitatively like those of ap+/ap+ males. However, the mean rate of nonwing courtship directed toward virgin wild-type females (i.e., the mean temporal frequency of these displays) is reduced in males homozygous for ap4, ap56f, or apc alleles. In contrast, the apblt allele makes for wild-type rates of nonwing courtship. Immature male sex appeal persists for at least 3 days in males homozygous for apc and, to a lesser extent, in ap56f or ap4 homozygotes; apblt/apblt and wild-type males lose immature male sex appeal after 1 day. All three male phenotypes map to the ap locus, which is therefore essential for the development of normal levels of male courtship and male mating success and for the timely loss of immature male sex appeal. For each phenotype, ap+ is dominant to ap alleles making for behavioral abnormalities, with a single exception (for rate of nonwing courtship, ap+/apc was low). For mating success and frequency of nonwing courtship, each allele pair exhibits at least partial complementation, except for ap4 and ap56f, which fail to complement. For immature male sex appeal, apc, ap4, and ap56f fall into the same complementation group. Juvenile hormone production is not correlated with effects on male reproductive behavior. PMID- 1503550 TI - Multiple regression analysis of twin data: a model-fitting approach. AB - The multiple regression methodology proposed by DeFries and Fulker (DF; 1985, 1988) for the analysis of twin data is compared with maximum-likelihood estimation of genetic and environmental parameters from covariance structure. Expectations for the regression coefficients from submodels omitting the h2 and c2 terms are derived. Model comparisons similar to those conducted using maximum likelihood estimation procedures are illustrated using multiple regression. Submodels of the augmented DF model are shown to yield parameter estimates highly similar to those obtained from the traditional latent variable model. While maximum-likelihood estimation of covariance structure may be the optimal statistical method of estimating genetic and environmental parameters, the model fitting approach we propose is a useful extension to the highly flexible and conceptually simple DF methodology. PMID- 1503551 TI - Genetic and environmental effects on type A scores in monozygotic twin families. AB - Monozygotic (MZ) twin pairs with spouses and children, altogether 787 subjects, completed the Jenkins Activity Survey (JAS). The observed correlations for the various sets of relationships fitted well with biometric models including only parameters for additive genetic effects and, for Type A and Job Involvement, assortative mating. There was no evidence of effects of the family environment (cultural transmission) or genetic dominance (nonadditivity). For all but the Hard Driving and Competitive scale, there was evidence of effects of sex-specific genes. The heritability estimates were, for males and females, respectively, .33 and .39 for Type A, .36 and .48 for Job Involvement, .20 and .52 for Speed and Impatience, and .13 (both sexes) for Hard Driving and Competitive. The estimates given here are deflated by measurement errors and should probably be corrected by multiplying by values in the neighborhood of 1.3. Even after correction, the results suggest that individual differences for Type A and related traits depend more on nonfamilial environment than on genes. PMID- 1503552 TI - Mouse models of human single gene disorders. I: Nontransgenic mice. AB - Mouse models of human genetic disorders provide a valuable resource for investigating the pathogenesis of genetic disease and for testing potential therapies. The high degree of resolution of linkage mapping in the mouse allows mutant phenotypes to be mapped precisely which, combined with the accurate definition of areas of homology between the mouse and human genomes, greatly facilitates the identification of mouse models. We describe here mouse models of human single gene disorders dividing them into three categories depending on the information available; phenotypic similarities, comparative mapping and identification of the underlying genetic lesion. PMID- 1503553 TI - The molecular biology of desmosomes and hemidesmosomes: "what's in a name"? AB - Desmosomes are junctions involved in intercellular adhesion of epithelial cells and hemidesmosomes are junctions involved in adhesion of epithelia to basement membranes. Both are characterised at the ultrastructural level by dense cytoplasmic plaques which are linked to the intermediate filament cytoskeleton of the cells. The plaques strongly resemble each other suggesting a relationship between the two kinds of junctions, as implied by their names. Recent characterisation of the molecular components of the junctions shows they are, in fact, quite unrelated implying that structural similarity is fortuitous. The molecular biology raises many fascinating problems relating to their structure and function. PMID- 1503554 TI - The molecular basis of the type 1 glycogen storage diseases. AB - Microsomal glucose-6-phosphatase catalyses the last step in liver glucose production. Glucose-6-phosphatase deficiency, now termed type 1 glycogen storage disease, was first described almost 40 years ago but until recently very little was known about the molecular basis of the various type 1 glycogen storage diseases. Recently we have shown that at least six different proteins are needed for normal glucose-6-phosphatase activity in liver. Four of the proteins have been purified and three cloned. Study of the type 1 glycogen storage diseases has stimulated investigations of the mechanisms of small molecule transport across the endoplasmic reticulum membrane and demonstrated the existence of novel endoplasmic reticulum transport proteins for glucose and phosphate. PMID- 1503555 TI - Does protein structure determine amino acid sequence? PMID- 1503556 TI - Polycomb and friends. PMID- 1503557 TI - A mammalian molecular clock? AB - The molecular clock hypothesis remains controversial more than a quarter of a century after it was first proposed. A variety of approaches have been applied to testing the molecular clock in mammals. In many of these studies apparent refutation of the molecular clock has been based on false assumptions about the pattern of mammalian evolution. With a few exceptions there now appears to be little evidence for variation in the rate of molecular evolution among mammalian lineages, although comparison of more genes and proteins among a greater variety of mammalian orders is needed before a definitive conclusion can be reached on the issue. PMID- 1503558 TI - Carrier detection of deletions in female relatives of X-linked disorders by non isotopic in situ hybridisation. AB - Recent studies suggest that a non-isotopic in situ hybridisation (NISH) approach can be successfully employed to investigate the carrier status of female relatives in families of selected patients with Duchenne muscular dystrophy (DMD) or Hunter syndrome, whose diseases are due to a specific X chromosome deletion. Whilst the majority of metaphase spreads from normal females show specific hybridisation signals on both X chromosomes when tested with either dystrophin or Hunter gene-derived probes, only one X chromosome in each metaphase spread will show the relevant hybridisation complex in female carriers of deletions involving the dystrophin or Hunter gene. Thus, the NISH method can be a valuable diagnostic tool for the detection of the carrier status of female relatives of patients with X chromosome deletions. PMID- 1503559 TI - Two proteins with ribosome-inactivating, cytotoxic and abortifacient activities from seeds of Luffa cylindrica roem (Cucurbitaceae). AB - Two immunologically distinct glycoproteins, with a molecular weight of 28,000 and 28,500 respectively, were isolated from seeds of Luffa cylindrica using a procedure that involved acetone precipitation, gel filtration on Sephadex G-75 and ion exchange chromatography on CM-Sepharose CL-6B. The proteins differed in the content of aspartic acid, threonine, proline and alanine but were otherwise similar in amino acid composition. The proteins were capable of inducing mid-term abortion in mice, inhibiting protein synthesis in a cell-free system and suppressing thymidine uptake by human choriocarcinoma cells. PMID- 1503560 TI - Novel fractionation of proteins using novobiocin as a precipitating agent: application to ribosomal proteins from the archaebacterium Sulfolobus acidocaldarius and Escherichia coli. AB - A fractionation method involving precipitation of proteins with novobiocin has been developed to separate ribosomal proteins of the archaebacterium Sulfolobus acidocaldarius. Four groups of proteins were obtained corresponding to those precipitated with 0.2, 0.5 and 1.0 mg/ml novobiocin and the proteins soluble at 1.0 mg/ml novobiocin. The same procedure was also successful for the fractionation of ribosomal proteins from Escherichia coli. Two dimensional gel electrophoresis showed that proteins present in each group were distinct with only a minor contamination of proteins from other groups. Our results indicate that proteins with similar charge and molecular weight can be separated by this method. This procedure may have applications for the fractionation of other complex protein mixtures. PMID- 1503561 TI - Purified uteroglobin lacks anti-proteinase activity. AB - Rabbit uteroglobin was purified from both uterine fluids and lung lavages by a combination of gel filtration and ion-exchange column chromatography. Anti trypsin and anti-papain activities were measured in the fractions of the eluates. Anti-proteinase activities were detected in minor contaminants eluting close to the uteroglobin peak but the protein itself was devoid of anti-proteinase activity. Ion-exchange-purified uteroglobin also lacked inhibitory activity of elastase, chymotrypsin or subtilisin. The presence of contaminants could explain the anti-proteinase activity reported occasionally for uteroglobin. PMID- 1503562 TI - Reconstitution of a purified and partially active low Km iodothyronine 5' deiodinase with phospholipids. AB - We previously reported the detergent-extraction and purification to homogeneity from rat liver microsomes of an iodothyronine 5'-deiodinase which differed from the type I enzyme in its molecular size as well as its Km, thiol responsiveness, and its expected sensitivity to the antithyroid drug, propylthiouracil. The specific activity enhancement (22-fold) of the delipidated enzyme was, however, relatively modest. We report here that the purified enzyme can be activated a further 25-fold by reconstitution in microsomal phospholipids and, to a lesser extent, in soybean phospholipids. The data suggest that a native lipid environment is necessary for proper conformation of the enzyme for optimal activity. PMID- 1503563 TI - Bovine erythrocyte glutathione S-transferase: purification, inhibition, and complex formation. AB - Glutathione S-transferase has been purified from bovine erythrocytes by affinity chromatography. The enzyme has an isoelectric point of 7.2, behaves as a 48-kDa protein composed of two identical subunits, and has an N-terminal sequence of PPYTIVYFPVQGR?EAMRMLL. This sequence, the amino acid composition, and the kinetic parameters suggest that the enzyme belongs to the pi-class of transferases. Hemins, porphyrins, and fatty acids form complexes with the enzyme and serve as effective inhibitors. Treatment of the transferase with N-ethylmaleimide, 3-amino 1,2,4-triazole, diethyl pyrocarbonate, or 2,3-butanedione inhibits transferase activity without altering tetrapyrrole binding. The role of the complexation and inhibition of glutathione S-transferase in erythroid metabolism has yet to be elucidated. PMID- 1503564 TI - Purification and characterization of the HPR protein of Pediococcus halophilus. AB - HPr protein, the ptsH gene product, of the phosphoenolpyruvate:sugar phosphotransferase system of Pediococcus halophilus was purified to homogeneity using heat and acid treatments, DEAE-Sepharose CL-6B and hydroxyapatite column chromatographies. The purified protein complemented the HPr activity of the phosphotransferase system in Staphylococcus aureus ptsH mutant cell lysate. The molecular weight was estimated as 6,500 by SDS polyacrylamide gel electrophoresis. The amino acid sequence of the amino-terminal part (1-44) of the native purified protein was highly homologous to those of HPr proteins from gram positive bacteria. Antiserum raised against the purified HPr protein specifically reacted with the Pediococcus halophilus HPr protein and did not cross-react with Staphylococcus aureus or Escherichia coli HPr proteins. PMID- 1503565 TI - A tentacle gel simplifies the purification of ceruloplasmin. AB - The mechanism of how chloroethylamine-treated agarose greatly simplifies the purification of ceruloplasmin (Cp) by preferentially binding this protein from blood plasma has been investigated. Chloroethylamine readily cyclizes to ethylenimine under alkaline conditions which then polymerizes to polyethylenimine (PEI). Ethylenimine and PEI were detected in the reaction mixture used to generate the resin. PEI polymers are grown from the matrix and form "tentacle" ligands, while PEI-silica and PEI-cellulose which are not tentacle gels did not bind Cp as readily. Spermine and spermidine, naturally occurring polyamine compounds, were attached to CNBr activated-agarose and showed weak affinity for Cp. [It should be noted that ethylenimine is a potential human carcinogen and presents an inhalation hazard.] PMID- 1503566 TI - Rate laws for the exchange of guanine nucleotides bound to EF-Tu catalysed by EF Ts. AB - The rate laws governing the exchange of guanine nucleotides bound to EF-Tu catalysed by EF-Ts are set out and the information that is available from various studies is analysed in terms of the laws. In particular the consequences of k-1 being equal to k-4 in the reaction sequence as set out below are examined in relation to results obtained by Hwang and Miller (J. Biol. Chem. 260, 11498 11502) and the contradiction these pose in relation to other published results. Measurement of on and off rate constants for binding of GTP to EF-Tu.EF-Ts and of the affinity of EF-Ts for EF-Tu.GTP should prove of importance in resolving discrepancies. PMID- 1503567 TI - Isolation and purification of mitochondrial monoamine oxidase B from bovine liver by chromatofocusing. AB - Mitochondrial monoamine oxidase B has been isolated and purified from bovine liver. The isolation procedure involves (a) a series of purification steps including isolation of the mitochondria, extraction with non-ionic detergents and chromatofocusing; (b) a novel fluorimetric titration assay. The purified enzyme is isolated following a 8.8 fold purification with an overall yield of 12% and a specific activity of 3460 nM.g-1. A comparison is made with other established procedures. Ion exchange chromatography on DEAE-Cellulose produced a 6.8 fold purification, 6.2% yield and 2383.3 nM.g-1 specific activity while with affinity chromatography on Blue Sepharose CL-6B gave a 3 fold purification, 4.1% yield and a specific activity of 1152.7 nM.g-1. PMID- 1503568 TI - Membrane binding and autolytic activation of calpain-I in human platelets. AB - The binding of calpain-I (Ca2+ activated neutral protease with high Ca2+ sensitivity) to the membranes of human platelets and the subsequent autolytic activation of calpain-I were analyzed by an immunoblot technique. In A23187 stimulated platelets, cytosolic calpain-I translocated to the membranes with autolysis in a Ca2+ dependent manner and simultaneously underwent autolysis. Although calpeptin, a cell permeable calpain inhibitor, inhibited autolysis of calpain-I, it was unable to prevent the translocation of calpain-I. In a cell re constituted system, the membrane binding of calpain-I was also Ca2+ dependent and was significantly inhibited by a substrate of calpain. It was suggested that the binding of calpain-I to the membranes required the substrate binding site of this enzyme. PMID- 1503569 TI - [Protein motifs and their structure-functional role]. AB - The review deals with repeating fragments of amino acid sequences, so-called "motifs", that are important in maintaining structural integrity and/or function of various proteins, especially those interacting with phospholipid aggregates. The occurrence of Phe-Leu-Gly motif characteristic for the amino acid sequence of the primate immuno-deficiency viruses fusion peptides is analysed in various proteins, as well as tripeptide fragments of general formula Xaa-Xah-Gly (Xaa Phe, Tyr; Xab-hydrophobic amino acids Ala, Val, Leu, Ile) homologous to the above motif and retro-sequences Gly-Xab-Xaa. These tripeptide repeats are characteristic for the amino acid sequences of complex membrane proteins, viral envelope proteins, proteinases and proteins connected with energy transfer or interacting with lipids. These repeats are frequently met in conservative regions of amino acid sequences, in sites readily accessible for other molecules at the boundary of or between structured fragments, this being due to the backbone semi coiled form's preference in the given amino acid fragment. This protein motif appears to play an important role at the initial stages of the large protein's interaction with the phospholipid membrane. PMID- 1503570 TI - [Conformational aspects of the biological action of functional fragments of the p21ras oncoprotein family. 1. Fragments 1-11 and 9-16 of the polypeptide chain]. AB - Using theoretical conformational analysis, spatial structures of the N-terminal undecapeptide, common to all p21 modifications, and of the 9-16 fragments of the protein's active and passive analogues have been investigated. The data obtained reveal an essential differences between the predominant backbone forms of the active and passive modifications of the oncoprotein. PMID- 1503571 TI - [Conformational aspects of the biological effect of functional fragments of the p21ras oncoprotein family. 2. Fragment 1-16, various sequences]. AB - The conformational analysis data on active ([Val12-Gly13], [Asp12-Gly13] and [Gly12-Asp13]) and passive ([Gly12-Gly13] and [Pro12-Gly13]) modifications of the p21ras family oncoproteins are presented. The activating amino acid substitutions are shown to be accompanied by essential changes in the secondary structure, resulted in the 9-16 fragment spiralization. The spatial structure of the 1-9 fragment does not vary for all the predominant forms of the active and passive analogues. The results of the conformational analysis have been used for studying the structural-functional relationships. PMID- 1503572 TI - [Effective complementarily-addressed photomodification of nucleic acids by oligonucleotide derivatives, containing aromatic azido groups]. AB - Highly effective site-specific photomodification of a DNA-target was carried out with oligonucleotide reagents carrying aromatic azido groups. Oligonucleotide derivatives with a photoactive function R on the 5'-terminal phosphate and at C-5 atom of deoxyuridine were synthesized: R1NH(CH2)3NHpd(TCCACTT) and d(ULNHRCCACTT), where R1 is p-azidotetrafluorobenzoyl, R2 is 2-nitro, 5 azidobenzoyl, R3 is p-azidobenzoyl; LNH = -CH2NH-, -CH2OCH2CH2NH- or CH2NHCOCH2CH2NH-. The prepared compounds form stable complementary complexes and effect site-specific photomodification of the target DNA. The modification of pentadecanucleotide d(TAAGTGGAGTTTGGC) with the reagents was investigated. Maximum extent of modification strongly depended on the reagent's type, the photoreagent with R1 being the most effective. Whatever the binding site was, this agent provided a 65-70% modification in all cases except LNH = -CH2NH-, when the yield was twice lower. For the reagents bearing R1 the modification sites were identified. Selective modification at the G9 residue was detected in the case of LNH = -CH2OCH2CH2NH- and when a photoactive group was linked to the terminal phosphate. PMID- 1503573 TI - [Dependence of anti-acetylcholinesterase effectiveness of phosphoorganic inhibitors on the accessibility of the phosphorus atom]. AB - All equilibrium conformations of 12 anti-acetylcholinesterase organophosphorus inhibitors were calculated by the molecular mechanics method. The accessibility of the phosphorus atom of the inhibitors for interactions with the nucleophilic group at the enzyme active centre was estimated. The conformers with the phosphorus atom sterically accessible from the side opposite to the breaking ester bond were classified as productive. A correlation was revealed between the activity of the inhibitors and the population of their productive conformation. PMID- 1503574 TI - Otitis media. PMID- 1503575 TI - American Academy of Pediatrics AAP Task Force on Infant Positioning and SIDS: Positioning and SIDS. PMID- 1503576 TI - Naftifine treatment for dermatophytosis: multicenter clinical investigations in Turkey. Turkish Multicenter Dermatophytosis Study Group. PMID- 1503577 TI - What will become of Arctic medical research? PMID- 1503578 TI - Low birth weight in the central Canadian Arctic. AB - Birthing, health and prenatal records of 523 infants born between 1984 and 1988 in the central Canadian Arctic, were reviewed. The incidence of low birth weight (LBW) was 5.5%, which is lower than in many other populations. Principal indicators of risk were a previous history of a LBW infant, a short inter pregnancy interval, low weight at the time of the first prenatal visit and a weight gain of less than 200 gm/wk throughout pregnancy. Use of nicotine and alcohol may have been contributing factors. Although low, it is argued that the incidence could be further reduced through prepregnancy social and educational programs, as well as intensified prenatal care for those at risk. PMID- 1503579 TI - Infant mortality in Greenland: secular trend and regional variation. AB - Infant mortality and stillbirths were studied in the Inuit population of Greenland. Infant mortality rate decreased from 110 per 1000 live births in 1951 to 50 in 1970 and 20 in 1989. Statistically significant decrease was in particular seen for acute respiratory infections and certain perinatal conditions. Both perinatal and postperinatal mortality rates increased significantly with remoteness from the capital and were higher in settlements than in towns. The overall trend in Greenland is similar to the Danish pattern 30 years earlier, but there was pronounced regional variation. In towns, the infant mortality rate decreased continuously while in settlements an initial decrease was followed by a substantial increase during 1980-87 when the mortality rate doubled. The greater part of this increase could be attributed to an increased number of deaths in the postperinatal period countrywide during 1981-84 and an increased number of perinatal deaths in the settlements of one particular municipality during 1983-86. PMID- 1503580 TI - Influence of genetic and demographic factors on etiology and pathogenesis of chronic disease in north Siberian aborigines. AB - The relationship between genetico-demographic parameters (endogamy, inbreeding, mating structure, gene diversity) and regularities of the prevalence of hereditary and common diseases (ischemic heart disease, arterial hypertension) and their risk factors in the North Khanty, a small, semi-isolated Siberian ethnic group of Finno-Ugric linguistic affinities, were studied. It has been shown that among hereditary diseases autosomal-dominant and polygenic ones are most frequent. Special features of the genetic liability to common diseases were described. The contributions of hereditary factors to the total variability of the 20 studied morphophysiological traits were shown to vary significantly. PMID- 1503581 TI - The role of hereditary factors in phenotypic variability of hormone levels in the population genetically adapted to circumpolar environment. AB - The variability of the plasma cortisol, T3, T4, TSH and estradiol levels were studied in the North Khanty population genetically adapted to the extreme conditions of the North. The relationships between genetic markers and hormone concentrations were also studied. Negative linear correlations of T3 and T4 levels with age were obtained. Cortisol, estradiol and T3 levels showed nonlinear age dependency. T4 concentrations were significantly lower in August than in February and November. The highest heritability estimate was shown for estradiol levels (44%). PMID- 1503582 TI - The death divide: differentials in premature mortality by gender in Puerto Rico. AB - The use of the indicator "years of potential life lost" (YPLL) highlights the extent to which premature mortality in Puerto Rico is a predominantly male phenomenon. While men accounted for 58.6% of all deaths in 1987, they represented fully 71.8% of all YPLL attributed to the thirteen leading causes of death. The breakdown of YPLL by gender also underlines sex-specific differences in the causes of mortality. While accidents constitute the leading cause of premature death among men, malignant neoplasms take the lead among women. Similarly, homicides and cirrhosis are significant sources of years of life lost among males, while pneumonia/influenza and diabetes are higher priorities among females. These findings suggest that health promotion strategies need to be gender-specific in order to reach the right targets. PMID- 1503583 TI - [The social consequences of aging]. PMID- 1503584 TI - [Dr. Diego Alvarez Chanca introducer of universal medicine in America]. PMID- 1503585 TI - The new macrolides: expanding the ways in antibiotic treatment. AB - After almost forty years of its introduction, erythromycin will not be the exclusive member of the macrolide group of antibiotic agents, but a new generation of its derivatives which surpass it in pharmacological properties and clinical efficacy will also be available. Clarithromycin, a 14-membered derivative, has shown acid stability, longer half-life, lower protein binding and higher lung tissue penetration. Its exceedingly high activity against erythromycin-susceptible gram-positive cocci, Mycoplasma pneumoniae, and Legionella pneumophila makes it and important alternative choice in the therapy of respiratory tract infections. Also, it has shown high activity against Chlamydia trachomatis, and high urinary clearance of this unmetabolized molecule, important properties which would render it a special role in the treatment of genitourinary tract infections. Azithromycin, a 15-membered derivative has shown enhanced basicity (due to the nitrogen atom in its lactone ring), longer half life and lower protein bindings. Its exceptional activity against Hemophilus influenzae, Branhamella catarrhalis, Neisseria gonorrhoeae, Ureaplasma urealyticum and gram-negative bacteria, and its high concentration in tonsillar, pulmonary, prostatic and female reproductive tract tissues, assigns it an honorific place among the macrolides in the therapy against respiratory tract and genitourinary tract infections. Its role against T. gondii deserves further study, but points out this agent as a promise against this parasite. PMID- 1503586 TI - Disseminated histoplasmosis. AB - We have presented the microbiology, pathogenesis, clinical presentation, diagnosis and treatment of disseminated histoplasmosis. Emphasis is presented on the manifestations in the HIV infected patient. PMID- 1503587 TI - [Postoperative pain and the future]. PMID- 1503588 TI - AIDS Clinical Trials Information Service. PMID- 1503589 TI - [A biographical sketch of Dr. Arturo L. Carrion Pacheco]. PMID- 1503590 TI - Infected bullae: a recognizable entity. AB - Infected bullae are seldom diagnosed. They are frequently confused with pulmonary abscess. We present a case with a characteristic evolution. Bullae were identified previous to the infection. The illness developed gradually with scanty sputum, pleuritic pain and finally a febrile illness. Fever abated 48 hours after initiating two weeks of therapy with intravenous Clindamycin and Amikacin. As it is commonly seen, radiographic resolution was slow but it was complete in 8 weeks. Recognition of infected bullae is important to avoid inappropriate diagnostic or therapeutic interventions. PMID- 1503591 TI - Synthesis, hypoglycemic and toxicological evaluation of new 1,2-benzisothiazolyl derivatives. AB - The synthesis of 1,2-benzisothiazol-3-ylguanidines, 1,2-benzisothiazol-3 ylbenzensulphonylureas and 1,2-benzisothiazol-3-ylbenzensulphonamides is described. Some of the new compounds showed moderate hypoglycemic activity but most of them caused serious acute toxic effects. PMID- 1503592 TI - Controlled release of proteins and peptides from hydrogels synthesized by gamma ray-induced polymerization. AB - Hydrogels prepared by radiation-induced polymerization at a low temperature have been used as carriers for the controlled release of peptides and proteins. It was found that polymerization of 2-hydroxyethyl methacrylate in the presence of poly (ethylene glycol) methyl ether (MPEG) enabled the more porous and swellable matrics to be obtained, the higher the molecular weight of MPEG. As a consequence, protein release took place at an increasing extent and, provided that MPEG molecular weight was high enough, high molecular weight proteins could also be released. Such a state of affairs was not met in the case of hydrogels based on poly (2-hydroxyethyl acrylate). SEM analysis revealed that even high molecular weight MPEG did not give rise to any porosity, even though the degree of swelling was very high. As a result, no protein release was observed. It was therefore concluded that control of hydrogel porosity for the controlled release of large proteins is of overwhelming importance. PMID- 1503593 TI - Synthesis and evaluation of gastroprotective and antiulcer activity of some 2 substituted-1H-imidazo[4,5-b] pyridines and -1H-benzimidazoles. AB - Several compounds possessing imidazo[4,5-b]pyridine and benzimidazole structure bearing substituents in position 2 were prepared in order to evaluate an anti ulcer and gastroprotective activity in rat pylorus ligature, in comparison with omeprazole. Among sixteen compounds taken as representatives of the synthetised series only one (3d) showed a good activity by i.m. administration at 50 mg/kg, while by oral administration of 100 mg/kg a certain number was active and in some cases this activity was quite superior to that of omeprazole. PMID- 1503594 TI - Synthesis, spectral studies and biological activities of some N-bridged heterocycles derived from 3-arylaminomethyl-4-amino-5-mercapto-1,2,4-triazoles. AB - Synthesis of four 3-arylaminomethyl-4-amino-5-mercapto-1,2,4-triazoles starting from substituted anilines is described. These triazoles were employed in the synthesis of some N-bridged heterocycles carrying arylaminomethyl substituents. All the newly synthesized compounds were characterized by analytical, NMR and mass spectral studies. Some of the newly synthesized compounds were screened for their antibacterial and antiviral properties. PMID- 1503595 TI - Synthesis of some new fluorine bearing trisubstituted 3-thioxo-1,2,4-triazin-5 ones as potential anticancer agents. AB - In a search for new anticancer agents fluorine bearing trisubstituted 3-thioxo 1,2,4-triazin-5-ones (2-12) have been prepared and characterized by their elemental analysis, UV, IR and 1H-NMR spectral data. The in vitro anticancer activity of all the compounds has been determined. Compounds 3 and 7 showed a moderate activity against Leukemia/Lymphoma, Small/Non small Cell Lung, Colon carcinoma and Melanoma Cells. PMID- 1503596 TI - Synthesis and local anesthetic activity of some derivatives of N,N-dimethyl-2-(2 alkoxyphenylcarbamoyloxy)-1,1-dimethylethyl-ammonium chlorides. AB - A series of 8 new derivatives of 2-alkoxyphenylcarbamoic acid were synthesized and assayed for local anesthetic activity. The above compounds were isolated as hydrochlorides and their structure was proved by 1H NMR, 13C NMR and IR spectroscopy. The index of anesthetic activity of the compounds in infiltration and surface anesthesia increases with the length of the alkyl chain and, except for the C1-C3 congeners, all higher homologues proved to be significantly more active than the standard reference compounds, procaine and cocaine, respectively. Toxicity of the drugs decreases with increasing the chain length and is within acceptable limits. PMID- 1503598 TI - Cyclohepta[b]pyran derivatives with platelet antiaggregating and other activities. AB - The synthesis of some N,N-disubstituted 4-amino-6,7,8,9-tetrahydro-3 phenylcyclohepta[b]pyran-2(5H)-ones by reaction of phenylchloroketene with a series of N,N-disubstituted 2-aminomethylenecycloheptanones, followed by dehydrochlorination of the primary adducts with DBN, is described. Some compounds showed a platelet antiaggregating activity in vitro superior or comparable to that of acetylsalicylic acid, as well as weak local anesthetic, antiinflammatory and analgesic activities in mice and rats. PMID- 1503597 TI - Structure-activity studies on a 1,2,3-triazole derivative, a potent in vitro inhibitor of prostaglandin synthesis: the role of the heterocyclic ring. AB - This paper reports further structural modifications concerning the 1,2,3-triazole ring of the compound A, an effective in vitro inhibitor of prostaglandin synthesis. The introduction of different heterocyclic rings provided further information about of the role of the heterocyclic ring in enzymatic inhibition, as regards the number and position of the nitrogen atoms, the electronic effects, basicity, steric hindrance and hydrophilicity. The benzimidazole derivative 4e proved to possess a high enzymatic inhibitory activity. PMID- 1503599 TI - 1-Phenyl-1H-indazole derivatives with analgesic and anti-inflammatory activities. AB - The synthesis of 4-hydroxy-1-phenyl-1H-indazole-5-acetic acid 5 4-methoxy-1 phenyl-1H-indazole-5-yl-acetic acid 7 and 5-benzyl-1-phenyl-1H-indazol-4-ol 8, starting from 1,5,6,7-tetrahydro-1-phenyl-4H-indazol-4-one, is described. These compounds showed in mice an analgesic activity superior to that of acetylsalicylic acid and comparable to that of dipyrone; moreover, compound 5 exhibited an appreciable anti-inflammatory activity in rats. Grossbehavioral effects and acute toxicity in mice are also reported. PMID- 1503600 TI - Cannabinoid acids analysis. AB - The cannabinoid pattern of vegetable preparations from Cannabis sativa (hashish, marijuana) allows to recognize the phenotype of the plants, to be used as drug or for fiber. Cannabinoid determination by analytical point of view has represented some problems caused by the complex composition of the hexane extract. Capillary gas chromatography of the hexane extracts of vegetable samples, shows the presence of rather polar constituents that eluted, with noticeable interactions, only on polar phase. The compounds can be methylated by diazomethane and silanized (TMS) by silylating reagents. The methyl and methyl-TMS derivatives are analyzed by high resolution gas chromatography (HRGC) and by gas chromatography mass spectrometry (GC-MS). The identification of the compounds shows their nature of cannabinoid acids, which the main by quantitative point of view results the cannabidiolic acid (CBDA). It is known that the cannabinoid acids are thermally unstable and are transformed in the corresponding cannabinoids by decarboxilation. This is of interest in forensic analysis with the aim to establish the total amount of THC in the Cannabis preparations, as the active component. PMID- 1503601 TI - Red blood cell partitioning of gallopamil, verapamil and norverapamil. AB - In-vitro binding of calcium-antagonists gallopamil and verapamil (and its main metabolite norverapamil) to human red blood cells (RBCs) was investigated. The drugs are bound reversibly and dose dependent to RBCs in the same order of magnitude, with partition-coefficients of kRBC = 0.12-0.34 for gallopamil, kRBC = 0.10-0.30 for verapamil and kRBC = 0.10-0.27 for norverapamil. The data indicate that, although RBCs may act as subcompartments of the blood for this class of compounds, they may have no influence on therapeutic plasma concentrations, due to their low kRBC. PMID- 1503602 TI - Spectrophotometric determination of diltiazem in dosage forms. AB - A simple and reproducible method for determination of diltiazem in bulk and in dosage forms is presented. The method is based on formation of hydroxamic acid, which reacts with iron (III), forming a complex with a maximum absorption at 525 nm. Assay procedure for diltiazem dosage form requires thin-layer chromatographic separation prior to colorimetric analysis. PMID- 1503603 TI - [Detection of an inhibition of benzo(a)pyrene and sodium azide induced mutagenesis by extracts from human feces]. AB - Low levels of mutagenic activities were detected in only 5-25% of the feces of people on a normal mixed-western diet, when feces were extracted by solvents and extracts were analyzed for mutagenicity with Ames' standard Salmonella/microsome assay. Since mutagens are know to be present in this type of diet and may be synthesized endogenously by bacteria in the large bowel, the question is if antimutagenic compounds mask the presence of genotoxic substances. We therefore tested the inhibition of known mutagens--benzo(a)-pyrene and sodium azide--by acetone/ethyl-acetate extracts of lyophilized feces in model experiments. These extracts completely suppressed the mutagenicity of benzo(a)pyrene and reduced the mutagenicity of sodium azide by about 60%, but were non-cytotoxic. Using gel filtration over Sephadex LH-20 and subsequent silica gel column chromatography we found that the inhibitors were polar organic compounds with molecular weights about 500 or more. The inhibitory effect could not be changed by esterification or saponification methods but was completely abolished by alkaline potassium permanganate oxidation. We therefore conclude that the antimutagenic activities might be identical with bile pigments. PMID- 1503604 TI - [The behavior of fiber-reinforced plastics during laser cutting]. AB - The pattern of the organic emissions, which are produced by processing of fibre reinforced plastics (epoxy resins reinforced by aramid and glass fibres and phenol resins reinforced by aramid fibre) with laser beam was studied and the concentrations of the main components determined. Despite the application of plastic materials with different chemical structures, the observed patterns are very similar. Mainly aromatic hydrocarbons are emitted, especially benzene and toluene, as well as some heteroatom-containing aromatic hydrocarbons (e.g. phenol). By use of oxygen as process gas the emissions during cutting of glass fibre reinforced plastics can be reduced, while they will be constantly high with aramid fibre reinforced plastics. PMID- 1503605 TI - Influence of the pH-value on the growth of Staphylococcus epidermidis, Staphylococcus aureus and Propionibacterium acnes in continuous culture. AB - A cutaneous isolate of Staphylococcus epidermidis, Staphylococcus aureus and Propionibacterium acnes was grown in continuous culture at varying pH-values ranging from 5.0 to 8.5. In terms of the specific growth rate as well as the bacterial density during the plateau phase there were remarkable differences. In particular, Propionibacterium acnes grew much better in the pH 6.0 to 7.0 range than in a more acidic or alkaline milieu. Staphylococcus epidermidis resembled Staphylococcus aureus showing no major difference at pH 5.5 and 7.0. These findings substantiate the hypothesis that minor changes of the pH in the pH 5.5 to pH 6.0 range as to be induced by chemically neutral or alkaline skin cleansers on the human skin surface can increase the number of propionibacteria but not staphylococci remarkably due to the relative alkalinity by itself. PMID- 1503606 TI - [Halogenated organic compounds in swimming pool water]. AB - 18 different swimming pool waters in the Bonn-Rhein-Sieg area were analysed for trihalogenmethanes, halogenated acetic acids, 2,2-dichloropropionic acid, dihalogenacetonitriles and chloral hydrate. Most substances mentioned above were determined in almost every sample reaching total concentrations up to 538 micrograms/l. Considering the results one can see that some of the main pollutants are polar organic compounds like di- and trichloroacetic acid as well as chloral hydrate. PMID- 1503607 TI - T cell activation and antigen presentation in human thyroid autoimmunity. AB - In 1983, a hypothesis concerning the relevance of class II expression and antigen presentation to the induction and maintenance of endocrine autoimmunity was published. This article reviews the evidence that has been marshalled to support this concept, both in man, chiefly in Graves' disease, and in murine systems. New data concerning the multiplicity of thyroid autoantigens recognized by in vivo activated thyroid infiltrating T cells are compatible with this concept since the thyroid epithelial cells are the source of these antigens. Whether other autoimmune diseases also employ the same mechanism remains to be ascertained, as does the initial trigger for the autoimmune process. PMID- 1503608 TI - Studies on the role of tumor necrosis factor in murine and human autoimmunity. AB - We have analyzed the roles of tumor necrosis factor alpha (TNF-alpha) in human systemic lupus erythematosus (SLE) and murine models of lupus as well as in type 1 diabetes in NOD mice. These studies suggest an important role for TNF-alpha in the pathogenesis of autoimmune disease. Rather than being involved mainly in the effector arm of the inflammatory process of autoimmune organ destruction, our data suggest a primary involvement in some of the basic mechanisms of the autoimmune process. Evidence has been presented that emphasizes the possibility of the involvement of this cytokine in the genetic predisposition to SLE. The data may imply that the effect of TNF on the immune system may be more relevant to the pathogenesis of the autoimmune disease than direct local effects at some target organs. Based on the data presented, one should be cautious in extrapolating the effects of this cytokine in various in vitro systems to the in vivo situation. PMID- 1503609 TI - The effects of cyclosporin A on non-T cell components of the immune system. AB - Cyclosporin A (CsA) is a potent inhibitor of cytokine (IL-2-IL-6, IFN gamma) production by CD4+ T lymphocytes stimulated via the T cell antigen receptor pathway. This action results in indirect inhibitory effects on the growth and differentiation of B lymphocytes (IL-4 and IL-6). Using experimental models, it has also been shown that the functional activities of mononuclear phagocytes (IFN gamma) and other antigen-presenting cells, production of mast cells (IL-3) and eosinophils (IL-5) and the activity of natural killer (NK) cells may be inhibited indirectly by CsA. In addition, however, CsA blocks B cell responses to Ca(2+) dependent signals (e.g., anti-IgM) downstream of phosphatidyl inositol diphosphate hydrolysis; Ca(2+)-independent responses (e.g., to LPS or IL-4) are largely unaffected. In general terms, the functions of macrophages are unchanged or reduced in the presence of CsA. These include phagocytic activity in vitro and in vivo, chemotactic migration, superoxide and H2O2 production, protein (including monokine) secretion and MHC gene product expression. Antigen presentation (e.g., by epidermal Langerhans cells) may be affected, especially at high drug concentrations. There is recent evidence that CsA inhibits mediator (histamine and prostaglandin) release from human mast cells and that mucosal mast cell numbers may be diminished in CsA-treated animals exhibiting graft-versus host disease or helminth infections. PMID- 1503610 TI - Cyclosporin monitoring: its role in autoimmune indications. AB - This paper describes some of the methodological problems related to the measurement of cyclosporin. The clinical value of the measurements following organ transplantation are discussed and those areas also applying to autoimmune indications are highlighted. It is concluded that the routine use of cyclosporin monitoring in samples from patients receiving the drug for autoimmune indications is unlikely to be of significant value as a guide to efficacy or toxicity. However, some settings, such as suspected poor patient compliance, for the avoidance of potential drug interactions and for research on the absorption of new formulations are considered to be useful applications of the methodology. PMID- 1503611 TI - The optimal use of cyclosporin A in autoimmune diseases. AB - The optimal use of cyclosporin (CsA) in autoimmune diseases aims at achieving the best risk/benefit ratio and ensuring the absence of potentially irreversible adverse effects, particularly with respect to the kidney [corrected]. The experience gained with CsA therapy in more than 3,000 patients with autoimmune diseases is the basis for the current recommendations: the initial dose should be the lowest effective one and not exceed 5 mg/kg/day in non-life-threatening conditions; treatment should be as brief as possible (2-4 months) in cases of inefficacy; once a satisfactory clinical improvement has been achieved, the treatment should be maintained in the long-term using the lowest individually titrated effective dose; the dose of CsA should be decreased when serum creatinine rises by more than 30% above pre-CsA level. Continuous clinical and biological monitoring (especially of blood pressure and serum creatinine) is mandatory as long as CsA is prescribed. When these conditions are fulfilled, CsA may be an effective and safe therapy for selected autoimmune diseases, even in long-term treatment. PMID- 1503612 TI - Timing of immunosuppression in the natural history of autoimmune diseases. AB - We have insufficient data to guide us to the optimal timing of immunosuppression in the natural history of any autoimmune disease. Moreover, there are differences among the many autoimmune diseases and the many drugs available for use. Nevertheless, certain principles have emerged. Prophylactic non-specific immunosuppression prior to the onset of the immune-mediated process often is of minimal benefit. Vigorous immunosuppression shortly after the onset of the immune mediated process is most effective; many agents are of benefit at such times. If the disease has progressed to substantial clinical involvement, certain drugs previously useful may no longer be effective. At such a time of moderately advanced clinical involvement, only selected agents may suppress the disease. With substantial loss of function of irreplaceable organs, or parts thereof, immunosuppression becomes progressively less effective. Such drugs can interfere with inflammatory processes, but are of little benefit after deletion of cells or scarring of an organ. Therefore, to have any benefit, immunosuppression must be instituted prior to the time of irreversible loss of critical organs or parts thereof. PMID- 1503613 TI - The case for early intervention in rheumatoid arthritis. AB - A case for early intervention in rheumatoid arthritis is presented on the basis of the following observations: (1) established rheumatoid arthritis of 5 years duration or more is a progressive disease in most patients; (2) most patients with rheumatoid arthritis already have evidence of permanent radiographic damage within the first 2 years of disease; (3) the morbidity and mortality of rheumatoid arthritis are predicted by baseline data indicating more severe clinical status, rather than drug toxicity or causes 'unrelated' to rheumatoid arthritis; (4) currently used therapies, even those documented to be effective in randomized controlled trials, are not effective in most patients over periods of 2 years or longer. It is not known whether earlier intervention will result in better outcomes. However, these phenomena suggest a need for studies to evaluate early aggressive intervention in rheumatoid arthritis. PMID- 1503614 TI - Immunologically specific treatment of spontaneous insulin-dependent diabetes mellitus of NOD mice. AB - This paper discusses the possibility of immunologically specific therapy of spontaneous autoimmune disease. The results of animal studies encourage optimism. PMID- 1503615 TI - Cyclosporin in the treatment of rheumatoid arthritis. PMID- 1503616 TI - Insulin autoimmunity: the rate limiting factor in pre-type I diabetes. AB - Type I diabetes is preceded by a series of autoantibodies including recently recognized subtypes of cytoplasmic islet cell antibodies (ICA) which we have termed 'restricted' and 'non-restricted'. Amongst the autoantibodies detected in prediabetics the antibodies to insulin are unique in that their levels correlate with the rate of progression to type I diabetes. The levels of insulin autoantibodies appear to be stably regulated prior to the appearance of ICA and the highest levels are associated with expression of DR4. The above studies have led to the hypothesis that an immune response to insulin is an early and central feature of anti-islet autoimmunity and that such as immune response when associated with loss of tolerance to other islet antigens (e.g. ICA) is pathogenic. PMID- 1503618 TI - Low-dose cyclosporin therapy of ocular inflammation: preliminary report of a long term follow-up study. AB - Cyclosporin A (CsA) is an effective therapy for severe intraocular inflammation but nephrotoxicity and hypertension are major side effects even in low dose in combination with oral corticosteroids and clinical studies on the long-term effects of low-dose CsA therapy outside the field of organ transplantation are lacking. This multicentre, open, longitudinal study has been established to evaluate the long-term efficacy and side effects of low-dose CsA therapy (initial dose less than or equal to 5 mg/kg/day, with a maximum dose of 7 mg/kg/day, and total treatment duration greater than 3 months) in severe ocular inflammation where conventional therapy had failed to control the disease or caused intolerable side effects. Visual response to treatment, clinical signs and symptoms of side effects, biochemical and haematological parameters have been recorded at 3-monthly intervals since January 1987 and will continue until December 1993. Data for 74 patients (age 35.5 +/- 16.6 years) and 293 follow up visits are presented in this preliminary report. [table: see text] Other side effects include (% of all visits): hypertrichosis (4.2), headache (2.8), cramps (1.8), arthropathy (1.8), paraesthesiae (1.8), abdominal pain (1.5), weakness (1.5), dyspepsia (1.4), nausea (1.4), others (4). PMID- 1503617 TI - The expanding use of immunosuppression in the treatment of non-infectious ocular disease. AB - Cyclosporin has been used for an increasing number of ocular indications. This review attempts to put into perspective the present scope of cyclosporin use in the treatment of ophthalmic disorders. This includes a review of randomized masked trials performed to date and work done to minimize and characterize cyclosporin induced renal toxicity. In addition, the ocular surface is an ideal target for topical cyclosporin therapy, and the status of this therapeutic approach is reviewed. PMID- 1503619 TI - Cyclosporin A in asthma therapy: a pharmacological rationale. AB - Lymphocytes play a central role in immunological reactions and control the mobilisation and recruitment into lung tissue of eosinophils and mast cells. Since cyclosporin A can profoundly influence lymphocyte activation, it is appropriate to consider this drug as a novel anti-asthma therapy. Inhalation of low doses of cyclosporin A strongly inhibits the influx of inflammatory cells into the airways during acute allergic reactions, even though associated bronchospasm and airway hyper-reactivity are undiminished. It is suggested that cyclosporin A will be an effective anti-asthma therapy with an anti-asthma profile resembling that of established glucocorticosteroids. PMID- 1503620 TI - Post-thymic tolerance to self antigens. AB - There is now convincing evidence for the imposition of self-tolerance by means of the clonal deletion of self-reactive T cells operating within the thymus. Since not all self components may be encountered there, the question must be asked whether tolerance can occur post-thymically. To test this, we have used transgenic technology to direct expression of a known 'non-self' gene, H-2Kb, to the insulin producing beta cells of the pancreas of mice. H-2Kb-bearing skin, but not skin from other mouse strains, failed to be rejected by the 'RIP-Kb' transgenic mice indicating specific tolerance. Following in vitro stimulation, their spleen cells could not kill H-2Kb-bearing targets, but could respond to third party targets. Their reactivity to H-2Kb was restored by providing them with IL-2. Two hypotheses could account for the above: tolerance results either from the deletion or functional silencing of high affinity effector cytotoxic cells or of regulatory, IL-2-producing helper T cells. Since it is difficult to distinguish between these, we have produced a second series of transgenic mice with rearranged T cell receptor (TCR) genes encoding an anti-H-2Kb TCR, and obtained 'double transgenic' offspring by mating these mice with RIP-Kb mice. The TCR utilized the V beta 11 segment which can be detected by a monoclonal antibody. Although the double transgenic mice were tolerant of H-2Kb, there was no evidence of deletion of anti-H-2Kb T cells. It seems, therefore, that a non deletional mechanism operates to induce post-thymic tolerance.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1503621 TI - A multicenter randomized study comparing cyclosporin-A alone and antithymocyte globulin with prednisone for treatment of severe aplastic anemia. The cooperative group on the treatment of aplastic anemia. AB - This article reports the results of a randomized multicentric study comparing the efficacy of antithymocyte globulin (ATG) with cyclosporin-A (CsA) as first line therapy for severe aplastic anemia (SAA). Patients were randomized to receive ATG and prednisone (PDN) or CsA; hematological response and toxicity were compared. At 3 months, patients who had no or minimal response received the alternative therapy in order to assess the value of a sequential immunosuppressive therapy for treatment of severe aplastic anemia. One hundred and sixteen patients were analysed, 60 received CsA and 56 received ATG/PDN. The actuarial survival was 55% with a median follow-up time of 19 months. There was no significant difference in survival between the two groups. The main prognostic factor was the absolute neutrophil count (ANC) at entry: patients with ANC less than 0.2 x 10(9)/L had a significantly lower survival when compared with patients with an ANC greater than 0.2 x 10(9)/L (P = 0.0001). At 3 months, 16% of patients had a complete or partial response and a cross-over treatment was given to 68 patients. At 12 months, 77 patients were alive, with a complete or partial response in 47 patients. Patients who had responded to the first treatment had a better recovery of bone marrow failure than those who had a sequential immunosuppression. The main complication was infection which was more often observed and was more often lethal during ATG and PDN. This study demonstrates that CsA is comparable to ATG for primary treatment of SAA, but it is less toxic with fewer infectious deaths.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1503622 TI - Psoriasis: immunopathology and long-term treatment with cyclosporin. AB - Psoriasis is a disorder of abnormal keratinocyte proliferation mediated by T lymphocytes. Initiation of psoriasis is associated with an influx and activation of CD4 T lymphocytes into the dermis and epidermis, and resolution with an influx and activation of CD8 T lymphocytes within the epidermis. As a result of these observations it was postulated that cyclosporin (CsA) should prove to be an effective treatment for psoriasis. A total of 82 patients with psoriasis have been treated with CsA. Thirty patients with moderate disease were treated for periods up to 12 weeks, and comprised a short-term study. Two groups have been treated with long-term CsA. A group of 18 patients have been treated for greater than 1 year but less than 3 years, (mean 2.1) and a group of 10 patients for 4.0 5.5 (mean 5) years. A total of 15% of patients can be maintained on less than or equal to 2 mg/kg/day; 55% on 3 mg/kg/day, 80% on 4 mg/kg/day, and 92% on 5 mg/kg/day. Hypertension occurred in 17% of patients in the short-term study, 29% in the 2.1-year group and 44% in 5-year group. Blood pressure returned to normal in all hypertensive patients when CsA was discontinued for 1 month. Nephrotoxicity was assessed by serum creatinine levels and glomerular filtration rate (GFR) and renal biopsy in the 5-year group. In the short-term group there was no significant rise in the serum creatinine.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1503623 TI - Cyclosporin for palmoplantar pustulosis. AB - Palmoplantar pustulosis (PPP) is a chronic skin disease characterized by persistent erythematous, scaly plaques incorporating sterile pustules on palms and soles, which is resistant to most treatments. Recently, two published uncontrolled studies suggested that cyclosporin (CsA) could be an effective treatment for PPP. Similarly, an unpublished, randomized, placebo-controlled study showed that CsA is effective in preventing new pustule formation in PPP. In the present paper we review the treatment of PPP with special emphasis on CsA treatment. PMID- 1503624 TI - Extension of indications of immunosuppression in inflammatory bowel disease. AB - Treatment of the two chronic inflammatory bowel diseases (IBD), Crohn's disease (CD) and ulcerative colitis (UC) is still hampered, because we do not understand the pathophysiological processes behind them. Are they caused by a normal inflammatory response reacting towards a foreign agent, or are they caused by an abnormal inflammatory response against a common or even universal agent? Our only choices at present are symptomatic treatments, including immunosuppressive drugs. To make the necessary controlled testing of new immunosuppressive drugs ethically acceptable, we have to choose carefully between different designs: comparing a new drug against placebo in overall treatment failures, to add the new drug or placebo to ongoing treatment (addition design), or to apply a classical group comparison between test drug and placebo in moderately active cases. There exists a strong need for extension of indications for immunosuppressive and anti inflammatory treatments: to be able to treat long-term instead of short-term, to do without extensive surgery in some UC cases, to treat severe UC cases with isolated distal involvement, to treat CD patients with short bowel syndrome, and to treat CD patients with fistulae and severe extra-intestinal manifestations. Future drug treatment of IBD will probably still be based on immunosuppressive and anti-inflammatory drugs, while waiting for a pathophysiological breakthrough in these two diseases. PMID- 1503625 TI - Immunointervention in primary biliary cirrhosis: an overview. AB - Since autoimmune processes are probably involved in the early stages of primary biliary cirrhosis (PBC), immunomodulatory drugs have been investigated with the aim of prolonging survival, delaying transplantation, slowing histological progression and relieving symptoms. Corticosteroids, azathioprine, chlorambucil and, more recently, cyclosporin A and methotrexate have all be subjected to clinical investigation. In the latest of these, a European multicentre trial, cyclosporin A has been shown to delay death or transplantation with a reduction in liver related deaths and slowing of the rise of serum bilirubin. The incidence of nephrotoxicity and hypertension are low at the doses used. PMID- 1503626 TI - Immunointervention with cyclosporin A in autoimmune neurological disorders. AB - Cyclosporin A has proven a remarkably effective compound in suppressing disease activity in a number of animal models of autoimmune neurological disorders. During the last decade a number of controlled clinical trials have been carried out in human neurological disorders which are considered to be immune-mediated. The results of those trials are reviewed. PMID- 1503627 TI - Treatment of the nephrotic syndrome with cyclosporin A. AB - The three main causes of primary nephrotic syndrome are minimal change nephropathy, focal glomerulosclerosis and membranous nephropathy. Corticosteroids obtain remission of proteinuria in most patients with minimal change nephropathy. Many patients, however, show either frequent relapses or steroid dependency. A short course of cyclophosphamide or chlorambucil can achieve stable remission in many of these patients but alkylating agents cannot be repeated, their toxicity being cumulative. Analyses of the available studies showed that some 80% of patients can be maintained in remission with cyclosporin A (CsA) but relapse occurs when the drug is stopped. Severe side effects are rare. In particular, the mean values of creatinine clearance did not deteriorate in cyclosporin-treated patients and repeat renal biopsy showed only mild changes in some patients. There is no definite treatment for focal glomerulosclerosis. An analysis of 10 clinical trials showed that some 17% of nephrotic patients may enter complete remission of proteinuria and another 13% may attain partial remission of the nephrotic syndrome with CsA. There is concern over the use of this drug since cases of irreversible renal dysfunction have been reported. However, retrospective reviews of the available studies showed that the mean serum creatinine levels did not modify if patients had normal renal function when given CsA. A 6-month course of methylprednisolone and chlorambucil may obtain remission of the nephrotic syndrome in some 60% of patients with membranous nephropathy. Some trials have shown that CsA may improve proteinuria and there is also some suggestion that the drug might protect against renal function deterioration. Thus, when given at correct doses, CsA may exert an anti-proteinuric effect without deteriorating renal function, suggesting that the drug may represent a further tool in treating the primary nephrotic syndrome. PMID- 1503628 TI - Treatment of idiopathic nephrotic syndrome with cyclosporin in children. Preliminary results of growth data in long-term use. PMID- 1503629 TI - Pharmacokinetic strategies for cyclosporin therapy in organ transplantation. AB - Marked interindividual variations in cyclosporin (CsA) produce disparate clinical results in organ transplant recipients. In an attempt to eliminate marked deviations of insufficient or excessive CsA concentrations consequent to the administration of uniform drug doses, test dose pharmacokinetics were performed on each potential organ transplant candidate. An intravenous 3 mg/kg test dose delivered over 3 h proved to be readily performed, namely 53% perfect studies, and relatively reliable, namely 73% of observed concentrations within 10% of the predicted values. Furthermore, the use of CsA doses predicted by pretransplant studies reduces the incidence of delayed graft function, early rejection episodes and transplant loss. The oral test dose study predicted a suitable amount of CsA to achieve sufficient gastrointestinal absorption but was less accurate than the iv prediction method: namely, 40% of observed post-transplant concentrations were within 10% of the predicted target value. Furthermore, patients who received oral doses predicted by the test dose strategy showed no improvement in the incidence of acute rejection episodes between 7 and 60 days, and only modestly improved serum creatinine values. The lower accuracy of predictions from oral test dose studies may reflect the impact of non-linear oral (as opposed to iv) drug pharmacokinetics, of variable diet, and/or of altered postoperative gastrointestinal function. PMID- 1503630 TI - Immunological monitoring in organ transplantation and autoimmune disease. AB - The clinical manifestations of graft rejection or autoimmune disease represent the terminal phase in a complex sequence of inflammatory events. Although the spectrum of response to injury within each tissue is normally narrowly defined, the immune mechanisms involved may be heterogeneous, influenced by the immune status of the host, the nature of the stimulus (i.e. viral antigen, allostimulation, or aberrant recognition of self), and the use of exogenous immunosuppression. Within this framework, immunological monitoring is employed to distinguish the causative effector mechanisms, to characterize the disease course, to tailor therapeutic intervention, and to monitor treatment impact in individual immunological disorders. PMID- 1503631 TI - The effect of cyclosporin on renal function. AB - The depression of renal function caused by cyclosporin does not generally reflect permanent kidney damage but is caused by a reversible vasoconstriction, with no relevant changes in tubular function. Serum creatinine may remain within the normal range during therapy, but any decline in renal function can be detected by a rise in serum creatinine above the baseline value. Measurements of glomerular filtration rate before and during therapy have shown the degree of renal dysfunction in individual patients to correspond to their rise in serum creatinine. The cause of renal vasoconstriction is uncertain but animal experiments have highlighted several possibilities. These include: (1) albumin leakage with circulatory volume contraction; (2) enhanced Ca mobilization in contractile cells; (3) activation of a renin-like enzyme in vessel walls; and (4) renin accumulation in the renin-producing cells of the afferent arteriole. Such mechanisms, although seeming to operate at different doses, may act in unison at high doses, when renal function is most severely depressed. PMID- 1503632 TI - Serial kidney biopsies in patients with nephrotic syndrome treated with cyclosporin. AB - A total of 21 patients with severe steroid-resistant or steroid-dependent nephrotic syndrome have been treated with cyclosporin (CsA) over a period of 6 to 71 months. A permanent treatment was started in patients with complete [c] (proteinuria less than 0.3 g/day) or partial [p] (0.3 to less than 3.0 g/day) remission. In four cases proteinuria was markedly reduced but still greater than 3 g/day. Informed consent was obtained and all patients agreed to further control biopsies. Out of 14 patients treated for longer than 6 months, a fall in creatinine clearance was seen in three cases, including two patients with focal sclerosis who required dialysis treatment. Control biopsies were performed once in 11 and twice in seven patients. In two cases definite CsA-related damage was diagnosed after 1 and 24 months of treatment. Possible CsA-induced damage could not be excluded in three additional cases. In all other biopsies no CsA-related alterations could be demonstrated up to 47 months of treatment. The mean values of the creatinine clearance showed no deterioration. The drop off in a few cases has been related to the basic disease. PMID- 1503633 TI - Malignancy in autoimmune diseases. AB - Rheumatoid arthritis (RA) represents the autoimmune disease that has been most studied in relation to malignancy. An examination of all published cohort studies has indicated a 9.7-fold increase of non-Hodgkin's lymphoma among RA patients after immunosuppressive therapy, and a 2.5-fold increase in the absence of such treatment. Corresponding data for Sjogren's syndrome point to a similar contrast. These findings are inseparable from the hypothesis of impaired immunosurveillance which implies that malignancy is promoted by defects in the immune system. Studies of individuals treated with immunosuppressive drugs, particularly to prevent graft rejection, have indicated that immunosurveillance operates only against a restricted range of neoplasms. These include non-Hodgkin's lymphoma (NHL), squamous cell skin cancer, Kaposi's sarcoma and cervical carcinoma. Other states of immune impairment including AIDS are also associated with marked increases of NHL. There is a striking correspondence between malignancies for which there is epidemiological or laboratory evidence for a virus aetiology and those that are increased by immune impairment. In this respect the epidemiological evidence accords with experimental work that immunosurveillance primarily operates against neoplasms of viral origin. It is therefore possible that a viral aetiology also underlies the excess of NHL in certain autoimmune disorders, particularly after immunosuppressive therapy. PMID- 1503634 TI - Specific and non-specific autoreactive immunity. AB - Most autoimmune diseases are HLA-associated which supports the notion that they are dependent upon specific immune activation of a limited set of T cell clones. Findings which imply that induction of autoimmune reactivity probably does not differ from normal immune responses are discussed. The possibility of transferring autoimmune disease using T cell clones indicates that target structures for auto-immune attack are also present in healthy individuals. In the present article, it is argued that autoimmune reactions and immunity against nominal conventional antigens in principle are effected and regulated by similar mechanisms. It is assumed that persistent tissue damage occurs if immune attack is directed against tissues that cannot be regenerated, such as in diabetes, or are only slowly reconstituted, such as in rheumatoid arthritis. Normal immune responses are regulated by various inflammatory mediators and cytokines/interleukins. The joint of patients with rheumatoid arthritis is discussed as a model for propagation of immune reactions and tissue destruction in autoimmune disease. Of the different cytokines which are present in the synovial fluid or produced by cells in the synovial tissue, most are presumed to have originated in macrophages/monocytes such as IL-1, IL-6, IL-8, TNF-alpha and TGF-beta. Even so, T cells are believed to have an important role for the continued reactivity associated with autoimmune disease. This discrepancy can be explained in different ways. T cell products might escape detection because they are short-lived, they are immediately consumed or they are produced only during short time intervals.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1503635 TI - HLA class II disease associations: molecular basis. PMID- 1503636 TI - Generation of mutant mice lacking surface expression of CD4 or CD8 by gene targeting. AB - With the use of homologous recombination in embryonic stem cells, two new strains of mice lacking surface CD4 or CD8 expression have been generated. It is hoped that they will be useful mouse strains for the study of autoimmune diseases, tissue transplantation rejections and tumour rejections. PMID- 1503637 TI - Inhibition of T cell activation by MHC blockade: a possible strategy for immunointervention in autoimmune diseases. AB - Autoimmune diseases result from the activation of self-reactive T cells induced by autoantigens or by foreign antigens cross-reactive with an autoantigen. A striking characteristic of autoimmune diseases is the increased frequency of certain HLA alleles in affected individuals. Moreover, as demonstrated for example in rheumatoid arthritis and insulin-dependent diabetes mellitus, class II alleles positively associated with autoimmune diseases share amino acid residues in the hypervariable HLA regions involved in peptide binding. Therefore, it is likely that disease-associated HLA class II molecules have the capacity to bind the autoantigen and present it to T cells, thereby inducing and maintaining, under appropriate conditions, the autoimmune disease. The data reviewed here demonstrate MHC-selective inhibition of antigen-induced T cell responses in vivo by parenterally administered soluble, MHC-binding peptide competitors, under conditions in which the competitor is not immunogenic. This suggests the feasibility of a therapeutic approach based on blockade of MHC class II molecules in the treatment of HLA-linked autoimmune diseases. PMID- 1503638 TI - T cell receptor peptide therapy for autoimmune disease. AB - Synthetic peptides corresponding to germline T cell receptor (TCR) V beta sequences shared by encephalitogenic T cells can prevent and treat experimental autoimmune encephalomyelitis in rats. The operative mechanism apparently involves boosting of anti-TCR immunity that develops during the course of experimental autoimmune encephalomyelitis (EAE), leading to the induction of autoregulatory T cells and antibodies. Striking parallels are present between patients with multiple sclerosis and animals with EAE in the T cell frequency and TCR V gene bias of BP reactive T cells, suggesting the involvement of an encephalitogenic process in multiple sclerosis. Preliminary trials with the appropriate human TCR peptides indicate that anti-TCR immunity can be boosted efficiently and safely, with concomitant loss of BP response, thus providing an effective strategy for selective regulation of autoimmunity in man. PMID- 1503639 TI - Monoclonal antibodies as agents to reinduce tolerance in autoimmunity. PMID- 1503640 TI - Selective pressures and ras activation in carcinogenesis. PMID- 1503641 TI - Resistance of adult keratinocytes to differentiation-induced decrease in Ha-ras mRNA levels observed in newborn keratinocytes. AB - During two-stage mouse skin tumorigenesis, the mouse c-Ha-ras oncogene undergoes activation by point mutation after initiation with polycyclic aromatic hydrocarbons. Furthermore, initiated epidermal cells containing an activated Ha ras oncogene have been shown to be resistant to calcium-induced terminal differentiation. However, the relationship between Ha-ras expression and the differentiation process is not well understood in either normal or initiated cells. Before attempting to explore the role of Ha-ras expression in epidermal differentiation during tumorigenesis, we felt that investigation of Ha-ras gene expression in normal primary epidermal cells undergoing differentiation was warranted, since primary cultures of normal newborn and adult keratinocytes presumably contain the stem cells from which skin tumors arise. In the present studies, northern blot analysis was used to compare Ha-ras expression in normal newborn and adult epidermal cells undergoing differentiation. Steady-state levels of Ha-ras mRNA remained unchanged in primary cultures of normal adult epidermal cells during calcium-induced differentiation, whereas steady-state levels of Ha ras transcripts decreased during calcium-induced differentiation in primary newborn epidermal cells. Differentiation was induced by switching the adult and newborn keratinocytes from medium containing 0.05 mM Ca2+ to medium containing one of three different calcium concentrations (0.15, 0.5, or 1.2 mM Ca2+). The decrease in Ha-ras mRNA levels observed during differentiation in newborn keratinocytes occurred as an intermediate event in the differentiation process, was specific for the Ha-ras gene, and was not due to a general decrease in transcriptional activity during differentiation. Characteristic patterns of keratin 14 gene expression and cornified envelope formation were observed, verifying that the differentiation process had been induced in both the primary adult and newborn epidermal cells. That adult keratinocytes are resistant to the differentiation-induced reduction in Ha-ras mRNA expression observed in newborn keratinocytes may explain the difference in in vivo tumorigenic potentials of newborn and adult skin. PMID- 1503642 TI - Tissue-specific expression and induction of human O6-alkylguanine-DNA alkyltransferase in transgenic mice. AB - O6-Alkylguanine-DNA alkyltransferase (ATase) activity was determined in crude sonicates of tissues obtained from the F2 offspring of human ATase transgenic founder mice. In certain cases, samples were analyzed both before and after administration of zinc sulfate in the drinking water for 2 wk to upregulate the mouse metallothionein-1 promoter that controls the expression of the transgene. In liver samples obtained by partial hepatectomy, the ATase activities of nontransgenic mice ranged from 63 to 139 fmol/mg total protein (mean of 10 mice, 95.3 +/- 23 fmol/mg), whereas in positive transgenic mice, the range was from 503 to 2119 fmol/mg (mean of 10 mice, 963 +/- 475 fmol/mg). The difference between the mean ATase values for these two groups of mice is highly significant (P less than 0.001). All positive mice expressed ATase and in those examined using the human ATase coding sequence as a probe, isoschizomeric-restriction endonuclease digestion showed no evidence of cytosine methylation in the transgene. After zinc sulfate induction, the ATase levels in residual liver tissue were for the controls 84-191 fmol/mg (mean of 10 mice, 123 +/- 31.5 fmol/mg) and for positive mice 908-3273 fmol/mg (mean of 10 mice, 1960 +/- 724 fmol/mg). Induction thus caused a 1.4- to 3.2-fold increase in ATase activity in the tissues of individual transgenic mice (mean, 1.8-fold; P less than 0.003), with the greatest increase generally occurring in those mice that had the lowest preinduction levels. Hepatic ATase levels were thus increased up to 28 times higher in transgenic mice than in nontransgenic mice. When data from other groups of transgenic and nontransgenic mice (eight of each) was included and analyzed in an independent rather than paired fashion, the mean values for zinc-treated controls and transgenic mice, respectively, were 106 fmol/mg and 1415 fmol/mg, still a highly significant (P less than 0.001) difference. In two mice given a single intraperitoneal dose of cadmium chloride, hepatic ATase increased 2.1- and 4.9 fold, respectively. The effect of partial hepatectomy alone was also considered: for transgenic mice the mean ATase level increased from 453 to 661 fmol/mg protein after 48 h. In other offspring subjected to either unilateral nephrectomy or orchidectomy, induction of ATase activity by zinc sulfate was also seen in kidney (5.7- and 8.4-fold) and testis (1.7- and 3.1-fold), although these observations were made with small numbers of mice.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1503643 TI - Mutagenesis by apurinic sites in normal and ataxia telangiectasia human lymphoblastoid cells. AB - We used a shuttle vector based on the Epstein-Barr virus origin of plasmid replication (oriP) to determine the types of mutations induced by depurination in human cells. Plasmid DNA was incubated at pH 2 at 40 degrees C for various times to induce up to 20 apurinic (AP) sites per 9.7-kb plasmid and electroporated into lymphoblastoid cells derived from either a normal individual or an ataxia telangiectasia patient. After replication of the vector in the human cells, plasmid DNA was isolated and analyzed for mutations induced in the plasmid encoded herpes simplex virus type 1-thymidine kinase gene. Both the frequencies and types of mutations induced by depurination were essentially identical for normal and ataxia telangiectasia cells. The mutant frequency at 20 AP sites/plasmid was 10-fold to 13-fold greater than that observed for untreated DNA. Deletion and frameshift events accounted for 46-55% of the mutants induced by depurination. The induced deletions were relatively small (median size, 100 150 bp) and characterized by short (1-5 bp) regions of sequence homology at the endpoints. These mutations and the frameshifts, a majority of which occurred in runs of identical nucleotides, are consistent with a model involving AP-site induced template dislocation during DNA synthesis. A broad spectrum of base substitution mutations, which accounted for 19-36% of the induced mutants, was observed. The apparent preference for insertion opposite AP sites in human cells was G (43-55%) greater than A approximately C (18-21%) greater than T (9-14%). Our results in human cells contrast markedly with those published previously for the mutational specificity of AP sites in Escherichia coli, in which a large majority of the mutants resulted from insertion of an A opposite the abasic site. PMID- 1503644 TI - Analysis of point mutations in murine c-Ha-ras of skin tumors initiated with dibenz[a,j]anthracene and derivatives. AB - This study was designed to evaluate the point mutations in the murine c-Ha-ras gene of skin papillomas induced by initiation with dibenz[a,j]anthracene (DB[a,j]A), its bay-region anti-diol epoxide ((+/-)anti-DB[a,j]A-DE), and a 7,14 dimethyl analogue (7,14-diMeDB[a,j]A). Recent studies (Nair RV, et al., Chem Res Toxicol 4:115-122, 1991) in our laboratory have revealed both deoxyguanosine (dGuo) and deoxyadenosine (dAdo) adducts formed from the anti- and syn-diol epoxides of DB[a,j]A in cultured mouse epidermal cells after exposure to this hydrocarbon. Using PCR amplification and direct sequencing, we found specific A182----T transversion mutations (eight of 10 tumors) in codon 61 of c-Ha-ras in papillomas induced by initiation with DB[a,j]A. Analysis of papillomas generated by initiation with the more biologically potent analogue 7,14-diMeDB[a,j]A revealed that five of five tumors exhibited A182----T transversions in codon 61. The nature of the changes in the two DB[a,j]A tumors not showing codon 61 mutations in Ha-ras is currently not known since these tumor DNAs also did not possess c-Ha-ras mutations at codons 12, 13, or 59. Interestingly, papillomas produced by initiation with (+/-)anti-DB[a,j]A-DE also possessed A182----T transversion mutations in codon 61 of c-Ha-ras (five of five tumors). These data suggest that dAdo adducts derived from both parent hydrocarbons may play an important role in their tumor-initiating activity and possibly implicate a specific diol epoxide-dAdo adduct in this process. PMID- 1503645 TI - Activation of the Ki-ras gene in spontaneous and chemically induced lung tumors in CD-1 mice. AB - As part of an evaluation of the effectiveness of using ras mutation analysis for distinguishing carcinogen-induced from spontaneous tumors, we examined the profile of ras gene point mutations in spontaneous, 7,12 dimethylbenz[a]anthracene (DMBA)-induced, and N-nitrosodiethylamine (DEN)-induced lung tumors from Crl:CD-1(ICR)BR (CD-1) mice. Although all of the lung tumors were assayed for mutations in the Ha-ras, Ki-ras, and N-ras genes (codons 12, 13, and 61), only Ki-ras mutations were found, which is consistent with other studies that have noted a strong preference for Ki-ras gene activation in mouse, rat, and human lung tumors. We found that spontaneous CD-1 mouse lung tumors had a very high frequency of Ki-ras gene activation (17 of 20 tumors; 85%), distributed among codons 12 (5 of 20), 13 (1 of 20), and 61 (11 of 20). DMBA-induced lung tumors had a slightly higher frequency of Ki-ras gene mutations (16 of 16; 100%), again distributed among codons 12 (5 of 16), 13 (2 of 16), and 61 (9 of 16). However, seven of the DMBA tumors had mutations qualitatively different from those found in spontaneous tumors. In contrast to DMBA-induced tumors, DEN induced tumors had a lower frequency of Ki-ras mutations (36%) when compared with spontaneous lung tumors, suggesting that DEN primarily induces lung carcinogenesis by a mechanism other than ras gene activation. Thus, although spontaneous and induced CD-1 mouse lung tumors have a strong tissue-specific preference for carrying an activated Ki-ras gene, the nature of the initiating carcinogen can influence the frequency or profile of Ki-ras mutations. PMID- 1503647 TI - Fetal nuchal oedema: associated malformations and chromosomal defects. AB - During an 8-year period, oedema in the dorsal cervical region that produces a characteristic tremor on ballotement of the fetal head (nuchal oedema) was observed in 145 (7%) of the 2,086 fetuses that underwent karyotyping in our unit because of fetal malformations and/or growth retardation. Nuchal oedema was distinguished from nuchal cystic hygromata and from hydrops foetalis. In 132 (91%) of the cases with nuchal oedema, there were other fetal malformations, and 53 (37%) fetuses had chromosomal abnormalities, mainly trisomy 21 but also other trisomies, deletions or translocations, triploidy and Turner syndrome. Furthermore, the chromosomally normal fetuses with nuchal oedema had a very poor prognosis because, in many cases, there was an underlying skeletal dysplasia, a genetic syndrome or cardiac defect. PMID- 1503646 TI - Fetal abdominal hyperechoic mass: diagnosis and management. AB - In the last 2 years, we have had the opportunity to follow 12 cases diagnosed with hyperechoic abdominal masses. Four of the cases ended with a fetal demise, while 7 resulted in the birth of an anomalous or medically ill neonate. Only 1 case has shown spontaneous resolution of the hyperechoic mass with the birth of a normal neonate. The in utero diagnosis of a hyperechoic abdominal mass should encourage the clinician to further investigation since the differential diagnosis is quite diverse. Appropriate counselling for the patient is a necessary part of prenatal care. PMID- 1503648 TI - Strawberry-shaped skull in fetal trisomy 18. AB - During an 8-year period, a strawberry-shaped skull (flattening of the occiput with pointing of the frontal bones), was observed in 54 (3%) of the 2,086 fetuses that underwent karyotyping in our unit because of fetal malformations and/or growth retardation. In all 54 cases with a strawberry-shaped skull, there were other fetal malformations; in 43 (80%) fetuses, there was trisomy 18 and in 1 triploidy. Therefore, the ultrasonographic finding of a strawberry-shaped skull should initiate a diligent search for the presence of other markers of trisomy 18 and is a strong indication for fetal karyotyping. However, in the total series of 2,086 fetuses with malformations and/or growth retardation, there were another 40 fetuses with trisomy 18 and 41 with triploidy who did not have a strawberry shaped skull. PMID- 1503649 TI - Early prenatal diagnosis and therapy of fetal hypothyroid goiter. AB - We report a case of early diagnosis of iodide-induced fetal hypothyroidism at 22 weeks of gestation, confirmed at 29 weeks by cordocentesis and successfully treated intra-amniotically. The ultrasonographic feature was the presence of two echogenic masses in the fetal neck; polyhydramnios was absent. Mild hypothyroidism was diagnosed based on fetal serum obtained by percutaneous umbilical blood sampling at 29 weeks of gestation. The persistence of fetal hypothyroidism in spite of maternal thyroid improvement was confirmed by a second cordocentesis at 35 weeks of gestation, and a single injection of intra-amniotic levothyroxine (250 micrograms) was performed. The serial ultrasonographic examinations showed disappearance of the fetal goiter. A healthy female baby (3,630 g) was delivered at term. At birth, the thyroid gland was not enlarged, and neonatal thyroid hormones were within the normal range. This case suggests that cordocentesis is a reliable method to assess the fetal thyroid status; moreover a single injection of intra-amniotic thyroxine was effective in treating fetal hypothyroid goiter. PMID- 1503650 TI - Fetal cardiovascular physiology and therapy. AB - The ability to diagnose fetal cardiovascular malformations prenatally has been established during the past 14 years. This has naturally led to an increased interest in the possibility of providing timely therapy in the neonatal period and has raised the prospects for prenatal intervention. Before medical, catheter, and/or surgical interventions are performed, however, it is important to understand the normal and abnormal physiology of the fetal cardiovascular system. Significant insights have been gained into human fetal cardiovascular physiology utilizing data previously gleaned from fetal lamb models and correlating anatomic, pulsed Doppler, and color flow Doppler observations that have been made echocardiographically during the second and third trimesters of human fetal cardiac development. Regional blood flow distribution studies in the human have demonstrated a relative right-ventricular volume dominance in the human fetus of a somewhat lesser magnitude than previously described in the lamb. Observations of ventricular filling characteristics suggest a relative paucity of diastolic 'reserve' in the human fetal heart implying a relative sensitivity to acute volume overloading. The human fetal heart, like that of the fetal lamb, also appears to have a relatively modest amount of 'systolic reserve', making the heart particularly susceptible to acute ventricular afterload. Further studies have demonstrated the ability to recognize altered intrauterine shunt flow across the fetal ductus arteriosus and foramen ovale. As predicted in fetal lamb models, alterations in shunt flow accompany major malformation complexes including ventricular hypoplasia. Studies to date suggest that attempts at surgical intervention should be made very cautiously due to the inability to ascertain whether altered shunt flow patterns precede (cause?) or follow the development of structural abnormalities. PMID- 1503651 TI - Fetal therapy, ethics and public policies. AB - This article reviews the evolution of ethical problems in the first generation of experimental fetal therapy and the prevailing approaches to them. The problems include: review of risks/benefits, case selection, informed consent, twin pregnancies, and refusal of proven fetal therapy. The article further discusses ethical and public policy issues in the lack of U.S. federal support for fetal diagnosis, fetal therapy, and human embryo research. An argument is made for such support, beginning with experimental gene therapy in the fetus. Ethical principles are identified that support an obligation to learn to relieve and treat such human suffering at the earliest time. Contradictions of these principles are also identified in terms of research not now supported. PMID- 1503652 TI - Intrathoracic silo for the potential antenatal repair of diaphragmatic herniae with liver in the chest. AB - Antenatal correction of congenital diaphragmatic hernia in the human fetus is an attractive theoretical possibility that might reverse pulmonary hypoplasia before it becomes too severe for post-natal survival. Initial attempts at correcting these herniae in the human fetus have been beset with many technical problems, one of which has been to prevent acute obstruction to the ductus venosus when the left lobe of the liver is reduced back into the abdomen. We describe a new procedure intended to reduce the liver gradually so that the ductus venosus is never acutely kinked and more normal rib cage mechanics may be maintained. PMID- 1503653 TI - First trimester interfetal size variation in well-dated multifetal pregnancies. AB - Sonographic measurements of multifetal pregnancy for dating and growth are considered identical to singleton pregnancies until the second trimester. Observations in 57 patients having triplets or more, who were referred for first trimester multifetal pregnancy reduction, suggest considerable size variability both within an individual pregnancy and among pregnancies of the same gestational ages (GAs). These data are unique because the GAs are precisely known, because the pregnancies were established by assisted reproductive technology. We observed a greater standard deviation at 12 and 13 weeks of GA. We also observed significant interfetal variation within an individual pregnancy. Because multifetal pregnancy reduction was performed, follow-up of any given fetus to term was not possible. We conclude that for high-order multiple gestations: (1) interfetal size variability begins much earlier than often stated; (2) differences in the degree of variability can be observed among different pregnancies of the same gestational age and within the same pregnancy, and (3) there is a trend for increasing variability with increasing gestational age. PMID- 1503654 TI - Fetal cerebral blood flow velocity during labour. Preliminary report. AB - The authors have tried to ascertain in a preliminary study if monitoring of fetal cerebral blood flow velocity during labour could identify a situation threatening the fetal brain, which could justify a compulsory fetal extraction. Nine patients were explored at term during labour. The Doppler signal was recorded using the abdominal route at the level of the fetal internal carotid. The diastolic carotid index was used (DCI = D/S). In 5 cases, fetal heart rate (FHR) was normal during labour and the DCI was on average comparable for each of the patients and the mean DCI (20.1 +/- 1%) was in close agreement with the values normally seen after 33 weeks of amenorrhoea during pregnancy. The case of isolated deceleration shows that deceleration causes an almost instant drop in the telediastolic flux, but the index increases more rapidly than could be expected from the increase in cardiac frequency if this phenomenon were of purely cardiogenic origin. In the case of bradycardia, it was noticed that during the return to the initial FHR frequency, the DCI was much higher than during the measurements performed before bradycardia. In the 1st case of pathological FHR, the index was very high and remained elevated during all the observation period. The fetus presented at birth a normal Apgar score as well as normal blood pH and neurological examination. In the 2nd case of pathological FHR, the FHR was abnormal with decelerations, the DCI increased rapidly and remained high.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1503655 TI - Ventrolateral prefrontal cortex lesions in rats impair the acquisition and retention of a tactile-olfactory configural task. AB - Rats with aspirative lesions of the ventrolateral frontal cortex were tested on acquisition and postsurgical retention of an associative learning task that required that they learn a tactile-olfactory configural discrimination. The task required that they pull up a string to obtain attached food and that they identify the correct string using a compound of string size and odor. The rats were not impaired in initial learning or reversal of the olfactory elements of the discrimination. They were impaired in acquisition and retention of the compound, and their deficit was proportional to lesion size. The results confirm that the ventrolateral frontal cortex is involved in processing of olfactory information and imply that the prefrontal cortex is involved in at least certain types of cross-modal configural associative learning. PMID- 1503656 TI - Visual and auditory spatial and nonspatial delayed-response performance by Korsakoff and non-Korsakoff alcoholic and aging individuals. AB - Thirty-six male alcoholics (13 with Korsakoff's syndrome) and 24 controls performed visual and auditory delayed-response tasks sensitive to prefrontal cortical damage in nonhuman primates. Korsakoff patients were consistently impaired compared with other subjects. Impairments by Korsakoff patients were evident when demands were placed on visual processing time (brief stimulus durations), and the deficits became exaggerated with increased demands on short term memory. Under the most difficult experimental conditions, controls and non Korsakoff alcoholics who were over 50 years old performed somewhat worse compared with younger groups 27-49 years old. Age-linked deficits were mild compared with Korsakoffs' deficits, and age-group differences disappeared with easier task demands. The results implicate cortical pathology in alcoholism and normal chronological aging and suggest that prefrontal damage accompanies alcoholic Korsakoff's syndrome. PMID- 1503657 TI - Radio-frequency lesions of the thalamus produce delayed-nonmatching-to-sample impairments comparable to pyrithiamine-induced encephalopathy in rats. AB - Rats were trained and matched on a delayed-nonmatching-to-sample (DNMTS) task and randomly assigned to treatment. In Experiment 1, radio-frequency (RF) lesions were aimed at lateral portions of the internal medullary lamina (L-IML), midline thalamus (MT), mammillary bodies (MB), and the combination of MT and MB. In Experiment 2, RF lesions were aimed at the fornix. After recovery, DNMTS was retrained at retention intervals retention interval of 3.0-18.0 s, the critical retention interval for 75% DNMTS accuracy was determined by a staircase procedure, and spontaneous exploration was observed in an open field. L-IML lesions produced significant deficits on DNMTS and exploratory behavior that were comparable to deficits on the same tasks in rats recovered from pyrithiamine induced thiamine deficiency. Fornix lesions produced significant DNMTS deficits that were substantially smaller than for the L-IML group. The MT, MB, and MT+MB treatments had no significant effect on DNMTS. PMID- 1503658 TI - Eyeblink conditioning in the developing rat. AB - Long-Evans rat pups, 17-18 or 24 days of age, were trained with an eyeblink conditioning (EBC) procedure that was used previously with adult rats (Skelton, 1988). Pups received 3 sessions of delay conditioning in a single day at about 4 hr intervals (100 trials/session). Trials involved pairings of an auditory conditioned stimulus (2.8-kHz, 82-dB tone) and a periocular-shock unconditioned stimulus (US; 100 ms, 2 mA), which were presented 280 ms apart. EBC was observed at both ages, but older pups learned much more rapidly. Subsequent experiments established that this effect is associative (Experiment 2), that age differences in EBC cannot be attributed to differences in ability to respond or in sensitivity to the US (Experiment 3), and that EBC rate can be modulated by motivational state (Experiment 4). This preparation may help elucidate the relation between neural development and the ontogeny of learning. PMID- 1503659 TI - Learning-dependent timing of Pavlovian eyelid responses: differential conditioning using multiple interstimulus intervals. AB - This study demonstrates that individual animals can concurrently acquire differently timed conditioned eyelid responses using a differential conditioning procedure in which distinctive conditioned stimuli (CSs) are individually paired with an unconditioned stimulus, with each using a different interstimulus interval (ISI). This promotes robust conditioning, and the timing of the conditioned responses is appropriate for the respective ISIs, differs for each CS to the extent that the ISIs are dissimilar, and is apparent in individual trials. This procedure was used to demonstrate that response timing is not a function of associative strength. These data suggest response timing is mediated by an ability to make temporal discriminations during the CS. The within-animals comparisons made possible by this differential conditioning should facilitate lesion and unit recording analyses of the neural basis of response timing. PMID- 1503660 TI - Pelvic and pudendal nerves influence the display of paced mating behavior in response to estrogen and progesterone in the female rat. AB - Two experiments examined whether the pudendal and pelvic autonomic nerves are important for pacing behavior shown by the female rat during mating. Ovariectomized female rats received bilateral transection of the pudendal (Pux), pelvic (Pex), or pudendal and pelvic (Pu + Pex) nerves or were sham-operated (Shx). Lordotic behavior, precopulatory solicitations, postural adjustments, and pacing behavior were measured 14 days after nerve transection in Experiment 1 after sequential treatment with estradiol benzoate (EB) and progesterone (P) and in Experiment 2 on the day after 7 daily injections of EB. After combined EB and P treatment, disruption of pacing behavior occurred in Pex and Pu + Pex animals. After EB-only treatment, Pux animals as well as Pex and Pu + Pex animals showed decreased pacing behavior. Thus, afferent input via the pelvic nerve is important for the display of pacing behavior, and P may counteract the effects of autonomic nerve transection. PMID- 1503661 TI - Effects of unilateral hypothalamic manipulations on the sexual behaviors of rats. AB - Four experiments that assessed the contributions of each side of the hypothalamus to the control of sexual behavior found the following. (a) Exposing the left, but not the right, ventromedial nucleus to estrogen neonatally defeminized sexual behavior in female rats. This asymmetry did not reverse as sexual differentiation progressed. (b) Unilateral cuts lateral to the medial preoptic area disrupted mounting in females that had mounted regularly before surgery, when given testosterone. The deficits were greater when the cuts were on the left side, but a third of the females with unilateral cuts showed severe deficits regardless of the side. (c) Comparable cuts did not impair masculine sexual behavior in gonadally intact males. In fact, left-side cuts seemed to accelerate copulation in males. (d) Unilateral lesions of the ventromedial nucleus disrupted lordosis in female rats in an essentially all-or-none fashion. This effect did not vary with side. PMID- 1503662 TI - Control of ingestion by oral habituation in rat pups. AB - The role of habituation of mouthing activity in the control of ingestion was investigated in 6-, 12-, and 18-day-old rat pups. In pups at all ages, oral habituation to a flavored diet inhibited ingestion of a continuous oral infusion of that same diet. Twelve-day-old pups that had orally habituated to a diet continued to consume less of a continuous oral infusion of that diet both 30 min and 3 hr later, and the duration of suppressed ingestion was shown to be dependent on the rate of stimulus presentation during habituation experience. These data suggest that oral habituation may be a diet-specific influence on both intra- and intermeal patterning. PMID- 1503663 TI - Depletion of cortical norepinephrine in rats by 6-hydroxydopamine does not impair performance of a delayed-nonmatching-to-sample task. AB - Rats were trained on a spatial delayed-nonmatching-to-sample (DNMTS) task, matched for performance, and randomly assigned to treatment with dorsal noradrenergic bundle injections of either 6-hydroxydopamine, to deplete cortical norepinephrine (NE), or vehicle, to control for the effects of surgery. After recovery, there were no significant differences between the groups when retrained on the DNMTS task at retention intervals (RI) from 0.1 to 15.0 s. Furthermore, no differences were observed when rats were trained at a 6.0-s RI filled with distracting stimuli or when dummy information runs were added to increase proactive interference. These results demonstrate that depletion of cortical NE cannot account for the DNMTS performance deficits observed in rats recovered from pyrithiamine-induced thiamine deficiency (Knoth & Mair, 1991; Robinson & Mair, 1992). PMID- 1503664 TI - Chloramphenicol. Are concerns about aplastic anaemia justified? PMID- 1503665 TI - Recent developments in the management of paracetamol (acetaminophen) poisoning. AB - Paracetamol (acetaminophen) poisoning accounts for almost a third of admissions to our district poisons unit, and is the commonest cause of death in such patients. Antidotal treatment may be effective up to 10h after overdose with oral methionine or up to 24h with acetylcysteine (not 15h as previously suggested for the latter). Patients taking paracetamol overdose while also receiving drugs which induce hepatic enzymes are more susceptible to liver damage, and antidotal treatment may be necessary at lower plasma paracetamol concentrations (50% of the normal treatment line). As survival following liver transplantation is now increasing, it is important to identify early prognostic indicators in fulminant hepatic failure, so that those patients with a high chance of fatal outcome can be considered for transplantation. Useful indicators are the presence of acidosis, marked prolongation of prothrombin time or a continued rise in prothrombin time on day 4 after the overdose. There is no evidence that paracetamol or acetylcysteine are teratogenic in pregnancy. Delays in administering acetylcysteine after paracetamol poisoning in pregnancy have been shown to increase the risk of spontaneous abortion and fetal death. Thus, acetylcysteine should be started as early as possible where treatment is indicated. PMID- 1503666 TI - Adverse effects of local anaesthetics. AB - Local anaesthetics are responsible for 5 to 10% of all reported adverse reactions to anaesthetic drugs. Adverse effects may be classified as: (a) those associated directly with blocking ion channels in cell membranes, such as cardiovascular and CNS toxicity; (b) those due to other effects of drug or vehicle (mainly peripheral nerve complications); (c) allergic reactions (often a mistaken diagnosis); and (d) mechanical or other effects of technique, such as needle trauma or introduction of infection. Signs and symptoms of CNS toxicity include convulsions, followed by coma and respiratory depression. Convulsions are due to disinhibition of nervous conduction, probably by an action at the gamma aminobutyric acid (GABA) receptor complex, while depressant effects, which predominate at higher doses, are due to blockade of sodium channels. CNS toxicity is potentiated by hypoxia and hypercapnia, so acute management must minimise these. Cardiovascular toxicity also involves sodium channel blockade, reducing contractility and interfering with conduction. Bupivacaine differs from lidocaine (lignocaine) in the sudden occurrence of dangerous ventricular arrhythmias including fibrillation at subconvulsant doses. Ropivacaine is a newer amide local anaesthetic with toxicity intermediate between these but potency similar to bupivacaine. Neurotoxic complications leading to prolonged deficit after intraspinal administration are uncommon. Causes are multifactorial, and include pH of and additives to preparations. Allergic reactions account for only 1% of untoward reactions, but anaphylactoid collapse can be lifeth-reatening and requires rapid and effective management. PMID- 1503667 TI - Dextromethorphan. An overview of safety issues. AB - Dextromethorphan is a highly effective and widely used nonopioid antitussive drug. As it has been in use for more than 30 years, a large body of clinical experience has been used to formulate a safety profile. An anthology of adverse drug events has been analysed, drawn both from published case records and a data base recording dextromethorphan-related adverse events spontaneously reported by physicians or pharmacists. The resulting safety profile indicates that adverse drug reactions are infrequent and usually not severe. The predominant symptoms are usually dose related and include neurological, cardiovascular and gastrointestinal disturbances. Particular safety concerns arise when monoamine oxidase inhibiting (MAOI) drugs and dextromethorphan are coadministered. In addition to adverse drug reactions, the safety profile of dextromethorphan is affected by episodic and sporadic abuse. In fact, abuse appeared to be the most significant hazard identified by analysis of spontaneous adverse event reporting. No evidence could be found that the well documented pharmacokinetic polymorphism observed with dextromethorphan is correlated with any clinically significant safety risk if it is used for short term treatment. In summary, the safety profile of dextromethorphan is reassuring, particularly relating to overdose in adults and children. PMID- 1503668 TI - Mutagenicity of quinolone antibacterials. AB - The literature is summarised on the activity of quinolone antibacterial compounds in assays which are commonly used for risk assessment of new pharmaceuticals. These include assays for DNA damage, sister chromatid exchanges, chromosome aberrations and mutation induction. The general pattern of activity exhibited by these compounds is induction of DNA damage in both prokaryotic and eukaryotic cells, and induction of mutations in DNA repair-proficient bacteria and at the thymidine kinase locus in mammalian cells. They do not appear as a class to induce mutations at the hypoxanthine-guanine-phosphoribosyltransferase (HGPRT) or Na+,K(+)-ATPase loci or to cause chromosome aberrations. It is suggested that these actions may be the result of interference with eukaryotic topoisomerase and that this interference differs in some respects from the topoisomerase interference caused by certain antitumour compounds. The postulated mechanism of action has important implications for assessment of risk from consumption of quinolone antibacterials. The risk of adverse genotoxic events should vary directly with the concentration of drug reaching the intracellular enzyme target and the affinity of the drug for the target. Results of carcinogenicity studies conducted to date with the quinolone antibacterials suggest minimal risk from long term consumption of the newer, second-generation compounds. PMID- 1503669 TI - Comparative risk-benefit assessment of drugs used in the management of hypertension in pregnancy. AB - Antihypertensive treatment in pregnancy is needed to protect the mother from the dangers of severe hypertension (greater than or equal to 170/110mm Hg), particularly cerebral haemorrhage in the context of preeclampsia. There is no evidence that treatment of the hypertension confers any other benefit; the onset and progression of preeclampsia is neither prevented nor ameliorated. Therefore, there are no indications for treating mild-to-moderate hypertension (140 to 169/90 to 109mm Hg). Intravenous hydralazine and oral nifedipine are effective drugs to treat severe hypertension acutely, the latter having the advantage of ease of administration. For long term therapy, methyldopa is the only drug which has been fully assessed and shown to be safe for the neonate and infant. beta Adrenoceptor antagonists are safe to use in the third trimester but cause significant intrauterine growth retardation when used for longer periods. ACE inhibitors are contraindicated and diuretics should be avoided. Although calcium antagonists appear to have much potential they require further assessment of their use in pregnancy. PMID- 1503670 TI - Adverse reactions to drugs as a cause of admissions to a general teaching hospital in Hong Kong. AB - To determine the pattern of and the risk factors for adverse drug reactions (ADRs) in Hong Kong, a prospective study of acute admissions to 2 general medical wards at the Prince of Wales Hospital was undertaken. Of the 1701 admissions included in this study, 74 (4.4%) were attributed to ADRs. Sulphonylureas, nonsteroidal anti-inflammatories (NSAIDs) and insulin accounted for 61% of cases. The most frequent ADRs were hypoglycaemia (43%) and gastrointestinal haemorrhage (29.7%). Both old age and impaired renal function appear to be important risk factors for ADRs. In such situations, careful dose adjustments, use of an alternative drug or total avoidance may be necessary. Particular attention should be given to oral hypoglycaemic drugs and NSAIDs. PMID- 1503671 TI - A report of clozapine-induced agranulocytosis in the United States. Incidence and risk factors. PMID- 1503672 TI - HLA-associations in Leponex/Clozaril (clozapine)-induced granulocytopenia and agranulocytosis. Statistical viewpoints. AB - This paper describes a statistical analysis of the simultaneous occurrence of 48 human leucocyte antigens (HLAs) in an attempt to predict whether a patient treated with clozapine will develop granulocytopenia or agranulocytosis. Whereas the numerical results show that use of HLAs does not appear to satisfy the intended purpose, emphasis is placed on the statistical methodology recommended for a problem of this type. Other work in this area is critically discussed. PMID- 1503673 TI - Mechanisms of clozapine-induced agranulocytosis. AB - The aetiology of clozapine-induced agranulocytosis remains unknown. Leading candidates include an immune mechanism that is possibly complement- or drug dependent and a toxic mechanism. We analysed these mechanisms by culturing the granulocyte precursor stem cell from the bone marrow in the presence of patients' serum, clozapine or clozapine metabolites. Studies with patients' serum failed to identify an immune mechanism. On the basis of our preliminary data, it appears that a toxic mechanism may be responsible, and this is more likely to be due to a metabolite than to clozapine itself. Further studies are required to determine the sensitivity of bone marrow precursors to these clozapine derivatives. For instance, prospective collection of serum will make it possible to evaluate whether high metabolite concentrations develop in sensitive individuals and whether they are responsible for agranulocytosis. If such elevated levels occur, further studies will be required to determine whether prospective monitoring will effectively identify patients at risk and ultimately prevent the onset of agranulocytosis by early discontinuation of the drug. PMID- 1503674 TI - Clinical experience of clozapine-induced neutropenia in the UK. Laboratory investigation using liquid culture systems and immunofluorocytometry. AB - An incidence of drug-induced neutropenia of 2.5% has been found in the first 1000 patients to be treated with clozapine in the UK. The majority of affected patients experienced mild neutropenia (n = 22) with only 3 patients developing agranulocytosis. Data collected from these 25 patients suggest that the mechanism of neutropenia may be multifactorial. Laboratory investigation using liquid culture systems and immunofluorocytometry has identified clozapine and its major metabolite N-desmethyl clozapine as exhibiting toxic effects against myeloid maturation and myeloid mitotic compartments, respectively. Increased susceptibility to the toxic effects of clozapine was shown in 1 patient who had previously developed clozapine-associated neutropenia. No clinical or laboratory evidence of drug-induced antineutrophil or antimyeloid precursor antibodies was found. PMID- 1503675 TI - No direct clinical relevance of the human leucocyte antigen (HLA) system in clozapine-induced agranulocytosis. AB - The clinical use of clozapine in psychiatry is restricted by the associated risk of agranulocytosis. This risk is significantly higher than that associated with conventional antipsychotic medications. In order to identify a possible parameter to detect susceptible individuals before treatment, 103 patients with a history of clozapine-induced granulocytopenia or agranulocytosis and 95 matched control patients were typed for human leucocyte antigen (HLA)-A, -B, -C, -DR, -DQ and for a number of neutrophil-specific alloantigens. No significant association between certain HLA alleles or neutrophil antigens and susceptibility to clozapine induced granulocytopenia or agranulocytosis was observed. PMID- 1503676 TI - On the possible mechanisms and predictability of clozapine-induced agranulocytosis. AB - Studies were conducted on serum removed from 15 patients before, during, and after, clozapine-induced agranulocytosis. Cytotoxic studies were compared with samples taken from patients during treatment with clozapine who did not develop agranulocytosis or treatment controls (TC); additional controls consisted of allogeneic (NC) and autogeneic serum from apparently normal people. The effect of serum on measurable functions of polymorphonuclear neutrophils (PMNs) taken from normal people was tested. Procedures under study included suppression of post phagocytosis-induced 14CO2-indicated respiratory burst, as well as ejection of trypan blue by test PMNs. PMNs exposed to active agranulocytosis serum plus complement displayed diminished 14CO2 emission during phagocytosis or failed to eject trypan blue. PMNs exposed to serum of TC and NC continued to function normally as regards 14CO2 emission and trypan blue ejection. Five patients studied before the development of agranulocytosis showed suppressed PMN function, which increased to peak value during agranulocytosis and then disappeared within 40 days of recovery. Similar suppression of colony forming units of granulocytes and macrophages (CFU-GM) was found whenever agranulocytosis serum was included in the marrow culture. The cytotoxic material required complement for its full expression, was not dialysable, was neutralised by anti-IgM serum, and was absorbed by test PMNs. Furthermore, solutions of clozapine or 5 of its metabolites offered no similar suppression of PMN function in vitro after incubation in an aqueous medium or with normal serum. These observations favour development of an immunogenic clone in sensitive people during active treatment with clozapine, which eventually leads to precipitous depletion of PMNs and their precursors. The early appearance of this suppressive substance may offer an early warning for development of agranulocytosis. PMID- 1503677 TI - Possible role of free radical formation in drug-induced agranulocytosis. AB - The use of clozapine, a unique antipsychotic drug, has been restricted due to a 1 to 2% incidence of drug-induced agranulocytosis. Many other drugs, including paracetamol (acetaminophen), can cause agranulocytosis, although with a much lower incidence. Metabolic activation of these drugs by neutrophils or stem cells could be the molecular mechanism underlying this adverse effect. Drug oxidation by myeloperoxidase leads to free radical metabolite formation; these reactive free radicals can oxidise glutathione to a thiyl free radical, which in the presence of oxygen forms oxygen-derived free radicals. In contrast to glutathione, when these free radical metabolites oxidise ascorbate an unreactive free radical is formed, which does not even react with oxygen. In both reactions, the free radical metabolite is reduced to the original drug, although ascorbate is the more effective reducing agent. Thus ascorbate, when coadministered with agranulocytosis-causing drugs, may inhibit free radical chain reactions and other free radical-mediated reactions, such as protein adduct formation, and thereby prevent drug-induced agranulocytosis. PMID- 1503678 TI - Metabolism of clozapine by neutrophils. Possible implications for clozapine induced agranulocytosis. AB - Many types of adverse drug reactions appear to involve reactive metabolites which, by their very nature, usually have short biological half-lives. Therefore, reactive metabolites formed by neutrophils, or neutrophil precursors in the bone marrow, would seem more likely to be responsible for drug-induced agranulocytosis than metabolites formed in the liver. We have found that several drugs associated with a relatively high incidence of drug-induced agranulocytosis are metabolised by activated neutrophils to chemically reactive metabolites. In preliminary experiments with clozapine, we found that clozapine was metabolised by neutrophils. It also reacted with hypochlorous acid, the principal oxidant generated by neutrophils, to form a reactive intermediate. This intermediate has a half-life of 1 minute in buffer, but reacts very rapidly with glutathione. We believe that this intermediate is a nitrenium ion. Such a metabolite could be responsible for clozapine-induced agranulocytosis, either by direct toxicity or through an immune-mediated mechanism. PMID- 1503679 TI - Major histocompatibility complex associations with clozapine-induced agranulocytosis. The USA experience. AB - In order to determine associations between the major histocompatibility complex (MHC) and the development of clozapine-induced agranulocytosis, HLA typing was performed in a group of 42 clozapine-treated patients, of whom 11 had developed this adverse reaction. Among the patients with agranulocytosis, 7 (63%) were of Ashkenazi Jewish background and 4 (37%) were non-Jewish. An association between the HLA-B38, -DR4, -DQw3 haplotype and clozapine-induced agranulocytosis was found in all Jewish cases (7/7; 100%); in contrast only 4 of 21 (19%) Jewish control (nonagranulocytic) patients carried this haplotype. Among non-Jewish patients the HLA-DR2, -DQw1 haplotype was present in 4 of 4 (100%) patients with clozapine-induced agranulocytosis and in only 3 of 10 (30%) ethnically matched control patients. Our results indicate that gene products within the MHC could be involved in clozapine-mediated haematological toxicity. PMID- 1503680 TI - Retrovirus-induced immunodeficiency in the mouse: MAIDS as a model for AIDS. PMID- 1503681 TI - AIDS in prison: a review of epidemiology and preventive policy. PMID- 1503682 TI - HIV-1 western blot: development and assessment of testing to resolve indeterminate reactivity. AB - OBJECTIVE: To reduce the number of HIV-1 Western blot (WB)-indeterminates requiring follow-up and the time taken to provide a clear positive or negative result. DESIGN: In the first of two stages, a testing and follow-up strategy was developed to resolve anti-HIV-1 status of WB-indeterminates. In the second stage, implementation of this strategy was assessed. METHODS: After dividing indeterminates into four groups according to WB profile, samples were tested for anti-HIV-1, anti-HIV-2, anti-HTLV-I antibodies, and HIV-1 antigen using the most sensitive assays available. When testing failed to clarify anti-HIV-1 status, follow-up samples were taken to monitor changes in antibody status. RESULTS: Samples in two out of the four indeterminate groups were negative for anti-HIV-1. The other two groups required additional testing and/or follow-up to distinguish reactivity caused by anti-HIV-1 from cross-reactivity. CONCLUSION: Grouping HIV-1 WB-indeterminates according to profile allows a significant percentage to be reported as anti-HIV-1-negative, while additional testing may allow others to be reported as anti-HIV-1-positive. The remainder require a maximum of 3 months' follow-up to resolve anti-HIV-1 status. PMID- 1503683 TI - HIV-1 viral DNA load in peripheral blood mononuclear cells from seroconverters and long-term infected individuals. AB - OBJECTIVE: To determine viral DNA load in peripheral blood mononuclear cells (PBMC) from HIV-1-infected individuals. DESIGN: HIV-1 copy numbers were determined using a quantitative polymerase chain reaction (PCR), the PCR-aided template titration assay (PATTY). PATTY utilizes an internal plasmid control DNA, which is amplified within the same tube and using the same primers as the PBMC target DNA. HIV-1 copy numbers were confirmed by limiting-dilution PCR analysis. RESULTS: PBMC viral load of 19 long-term (greater than 4 years) HIV-1-infected individuals ranged from 0.8 to 100 copies per 10(3) PBMC. Significantly higher copy numbers were found among p24-antigen-positive than among p24-antigen negative individuals. In addition, the PBMC viral load of two HIV-1-infected individuals was monitored during the first 3 months after acute infection. For both patients, the HIV-1 copy numbers were shown to peak at the time of HIV-1 antibody seroconversion and decline subsequently (range, 0.6-10 copies per 10(3) PBMC). CONCLUSIONS: PATTY is a useful method for assessing the HIV-1 copy numbers in PBMC DNA. Viral DNA load peaks shortly after infection and reaches an individual specific level that is probably stable within a few months of infection. Viral DNA load in PBMC varies widely among long-term HIV-1-infected individuals. PMID- 1503685 TI - Multicentre quality control of polymerase chain reaction for detection of HIV DNA. AB - OBJECTIVE: Seven French laboratories tested the specificity and sensitivity of the polymerase chain reaction (PCR) for the detection of HIV-1 DNA. METHODS: Following its own PCR protocols, each laboratory independently tested blind two panels of 20 coded peripheral blood mononuclear cell samples collected from HIV-1 seropositive individuals and from HIV-1-seronegative individuals at high or low risk of HIV infection. For the first panel, laboratories were free to select type and number of primers; for the second, all were required to use the two primer pairs Pol 3/4 and MMy 9/10' (Nef 1). RESULTS: False-positive and false-negative results were observed in all laboratories (concordance with serology ranged from 40 to 100%). In addition, the number of positive PCR results did not differ significantly between high- and low-risk seronegatives. The use of crude cell lysates in DNA preparation produced the same PCR results as phenol-extracted DNA. Discrepancies between laboratories indicated that factors other than primer pairs contributed strongly to laboratory variability. CONCLUSIONS: Our results emphasize the importance of both positive and negative controls in PCR and demonstrate the value of multicentre PCR quality control. PMID- 1503684 TI - Relationship between cell-free viraemia, antigenaemia and antibody levels in HIV 1-infected Ethiopian patients. AB - OBJECTIVE: To determine the relationship and occurrence of cell-free viraemia, free or immune-complexed p24-antigen and p24-antibody levels in blood from HIV-1 infected patients in Ethiopia. METHODS: Peripheral blood was obtained from 66 Ethiopian and 137 Swedish HIV-1-seropositive patients. Blood samples were analysed for free or immune-complex bound p24 antigen by enzyme-linked immunosorbent assay before and after acid hydrolysis of immune complexes for infectious virus in plasma and peripheral blood mononuclear cells (PBMC), and for p24-antibody levels. We compared the kinetics of viral replication of Ethiopian with Swedish isolates in vitro. RESULTS: Infectious virus was isolated from PBMC in 95% and from plasma in 81% of Ethiopian AIDS patients. In contrast, p24 antigen was detected in only 5% of AIDS patients from Ethiopia, compared with 76% of those from Sweden. p24-antibody levels were much higher and more persistent in Ethiopian than in Swedish subjects. The ratio between reverse transcriptase activity and p24 antigen was significantly higher in Ethiopian isolate culture than in those of the Swedish isolates. CONCLUSIONS: Our results show that relationships between viraemia, p24 antigenaemia and p24-antibody levels in HIV-1 infected Ethiopian patients differ from those found in comparable Swedish patients. This pattern may partly explain the differences seen in the natural course of HIV-1 infection in Ethiopia and Sweden. PMID- 1503686 TI - Natural history of advanced HIV disease in patients treated with zidovudine. The Zidovudine Epidemiology Study Group. AB - OBJECTIVE: To describe the natural history of advanced HIV disease in patients treated with zidovudine. DESIGN: Longitudinal, observational study. SETTING: Twelve academic and community-based sites. PATIENTS, PARTICIPANTS: Eight hundred and sixty-three patients with AIDS or AIDS-related complex (ARC) with a CD4+ lymphocyte count less than 250 x 10(6)/l, who first received zidovudine between 15 April 1987 and 14 April 1988. MAIN OUTCOME MEASURES: Survival, progression to AIDS and first development of specific opportunistic illness. RESULTS: Median survival after initiation of zidovudine therapy ranged from greater than 900 days in patients with a baseline CD4+ lymphocyte count greater than or equal to 150 x 10(6)/l to 560 days in patients with a CD4+ lymphocyte count less than 50 x 10(6)/1. Other factors associated significantly with poorer survival were diagnosis of AIDS (versus ARC), baseline age greater than or equal to 40 years, hematocrit less than 35%, and diminished functional status. In patients with ARC at enrollment, median time of progression to AIDS ranged from 810 days in patients with a CD4+ lymphocyte count greater than or equal to 150 x 10(6)/l to 310 days in patients with a CD4+ lymphocyte count less than 50 x 10(6)/l. Rates of development of specific opportunistic infections or neoplasms and HIV encephalopathy were determined for different baseline CD4+ lymphocyte count ranges. Myelosuppression was significantly more common in patients with CD4+ lymphocyte counts greater than or equal to 100 x 10(6)/l. Sixty-five per cent of patients with a CD4+ lymphocyte count greater than or equal to 100 x 10(6)/l and 51% with a CD4+ lymphocyte count less than 100 x 10(6)/l continued to receive zidovudine 2 years after starting therapy. CONCLUSIONS: We describe the natural history of a cohort of patients treated with zidovudine for advanced HIV disease. These CD4+ lymphocyte count-stratified estimates of disease progression should provide prognostic information useful in the clinical management of advanced disease and the design of future studies. PMID- 1503687 TI - Parvovirus infection in children with AIDS: high prevalence of B19-specific immunoglobulin M and G antibodies. AB - OBJECTIVE: Investigation of the prevalence and pathogenic role of parvovirus B19 infection in Italian and Rumanian children with AIDS, compared with age-matched HIV-negative children (controls) with various recurrent infections of unknown aetiology. DESIGN: Detection of B19-specific immunoglobulin (Ig) M and IgG antibodies as the most indicative markers of past or current B19 infection. METHODS: B19 antibodies were detected by two enzyme immunoassays using synthetic peptide or recombinant protein, which corresponded to different B19 epitopes, as coating antigens. RESULTS: B19 IgM and IgG were seen in 10 out of 20 (50%) Italian and in 20 out of 51 (39.2%) Rumanian children with AIDS, in contrast to none out of 17 Italian and one out of 22 Rumanian controls (P less than 0.001). In addition, two Italian controls (11.8%), two Rumanian children with AIDS (3.9%), and two Rumanian controls (9.1%) had B19 IgM alone. Specific IgG alone was detected in eight (40%) Italian and 14 (27.5%) Rumanian children with AIDS, and in seven (41.2%) Italian and four (10.2%) Rumanian controls. CONCLUSIONS: While it is possible to attribute some B19 infections in Rumanian children to blood transfusion, the source was unknown for Italian children. However, in three of the Italian children who had B19 IgM and IgG persistently for 15-22 months, and in a 2-month-old Italian infant with B19 IgM and IgG, HIV might have activated a congenital or perinatally-acquired B19 infection. PMID- 1503688 TI - Changes in neuropsychological performance of AIDS-related complex patients who progress to AIDS. AB - OBJECTIVE: To investigate the changes in neuropsychological performance associated with progression from AIDS-related complex (ARC) to AIDS. DESIGN: A repeated measures design was used to compare three groups: ARC patients who progressed to AIDS (n = 15), those who did not (n = 19) and seronegative controls (n = 16). METHODS: The three groups were compared on tests of memory, information processing, motor performance, attention and conceptual flexibility. Clinical and immunological characteristics were recorded. Rates of neuropsychological impairment among the three groups were calculated and compared. RESULTS: The only significant difference between the groups at baseline was for one measure of motor performance. Repeated measures analysis indicated that there was a differential rate of change for the three subject groups for tasks of motor performance and attention. ARC patients who progressed to AIDS did not differ significantly from the non-progressors, although both groups showed significant deterioration over time compared with seronegative controls. Although there was a tendency for the progressors to have a higher rate of impairment, there were no consistent significant differences between visits. CONCLUSION: There were no significant changes in performance exclusively associated with progression to AIDS. PMID- 1503689 TI - Specific nutrient abnormalities in asymptomatic HIV-1 infection. AB - OBJECTIVE: To determine whether specific nutrient abnormalities occur in earlier stages of HIV-1 infection, thereby preceding the marked wasting and malnutrition that accompany later stages of the infection. DESIGN: A longitudinal investigation to determine biological, psychological and social factors thought to influence the progression and outcome of HIV-1 infection. Nutritional status was assessed using biochemical measurement of nutrient levels, dietary history, anthropometry and clinical examination for the signs and symptoms of nutritional deficiency or excess. SETTING: The study was performed on an outpatient basis at the University of Miami School of Medicine. PARTICIPANTS: One hundred homosexual men, aged between 20 and 55 years, who were asymptomatic other than persistent generalized lymphadenopathy (Centers for Disease Control stage III) and 42 age matched homosexual men demonstrated to be free of HIV-1 infection at two 6-month intervals. MAIN OUTCOME MEASURES: Biochemical measurement of nutrient status, dietary history, anthropometry, clinical signs or symptoms of nutritional excess or deficiency were obtained for all participants. RESULTS: Despite few differences in mean blood levels of specific nutrients, prevalence of specific nutrient abnormalities was widespread among HIV-1-infected subjects, compared with non-infected male homosexual controls. Overtly and marginally low blood levels of vitamins A (18%), E (27%), riboflavin (26%), B6 (53%), and B12 (23%), together with copper (74%) and zinc (50%) were documented in HIV-1-seropositive subjects. With the exception of riboflavin, zinc, and copper, a similar prevalence of abnormalities among HIV-1-seronegative controls was not observed. CONCLUSION: Specific nutrient abnormalities occur with relative frequency in asymptomatic HIV-1 infection and may contribute to the rate and form of HIV-1 disease progression. PMID- 1503690 TI - Experience with a totally implantable venous access device (Port-A-Cath) in patients with AIDS. AB - OBJECTIVE: To determine the complication rate of a totally implantable central venous access device [Port-A-Cath (PAC)] in AIDS patients, used mainly for home infusion therapy. DESIGN: A retrospective study. SETTING: The study was performed at the AIDS Unit of the Department of Internal Medicine, Academic Medical Centre, University of Amsterdam, The Netherlands. PATIENTS, PARTICIPANTS: Forty-seven consecutive AIDS patients who had a PAC device implanted to receive either drug maintenance therapy (42 patients) or total parenteral nutrition (TPN; five patients). RESULTS: Fifty-one devices were implanted between June 1987 and October 1990. Mean puncture frequency was five times per week. The total number of catheter days was 9069. The total complication rate was 0.43 per 100 catheter days. Complications occurred in 17 (36%) patients: three implantation-related bleedings (0.03 per 100 catheter days), three puncture-related bleedings (0.03 per 100), two infections (0.17 per 100), seven occlusions (0.08 per 100), four flow problems (0.04 per 100) and one central vein thrombosis (0.011 per 100). Imminent skin necrosis at puncture site occurred in one case (0.01 per 100) and drug extravasation in two cases (0.02 per 100). Eight devices (17%) had to be removed. Primary septicaemias were resolved using antibiotics in three out of six patients in whom they occurred. Occlusions were almost exclusively caused by TPN. CONCLUSION: A totally implantable venous access device appears to be safe and convenient in (home) infusion therapy in AIDS patients, without risk of additional infection. PMID- 1503691 TI - Anonymous HIV surveillance in Saughton Prison, Edinburgh. AB - OBJECTIVES: To estimate the prevalence of HIV by anonymous saliva testing in Her Majesty's Prison, Saughton (Saughton Prison), Edinburgh, UK. To elicit linked anonymous risk factor information from which to estimate risk scores for those who had taken an HIV blood test and, among drug injectors, for those who were HIV 1-antibody-positive on saliva testing. SETTING: Saughton Prison on 15 and 16 August 1991; HIV Immunology and Regional Virus Laboratories, Edinburgh, and the Medical Research Council Biostatistics Unit, Cambridge, UK. PARTICIPANTS: Male inmates (378 out of a total of 499) of Saughton Prison. MAIN OUTCOME MEASURES: Answers to a brief questionnaire about age, usual residence, present and past custodial sentences, drug injecting and sexual behaviour prior to and in prison, HIV testing and history of acute hepatitis. HIV-1-antibody status was established by saliva testing. RESULTS: Eighteen per cent of participants were injecting drug users (IDU), of whom approximately one-half (47%) had injected while inside prison. Ninety men (26%), including 40 (14%) of 278 participants who had never injected drugs and 77% of IDU participants, had taken an HIV blood test. Nine per cent of all participants and 35% of IDU participants had had an acute attack of hepatitis. Forty-one (62%) of 66 IDU had been imprisoned five or more times before their current prison sentence. After taking account of region of residence, injecting drug history and acute hepatitis, aspects of sentencing and sexual behaviour were not determinants of those who had been tested for HIV. On the study days, 18 out of 499 (3.6%) participants were known to prison medical officers to be HIV-infected. Following saliva testing, HIV prevalence was 17 out of 375 (4.5%) inmates tested. All 17 had at some time 'taken the blood test for HIV' and all had injected non-medically prescribed drugs. Edinburgh residence, age 26-30 years, have injected in prison and having first injected before 1983 all contributed to the risk score for whether an IDU was HIV-1-antibody-positive on saliva testing. CONCLUSIONS: Documented HIV prevalence in saliva was 4.5%, which--assuming no volunteer bias (as supported by questionnaire returns)- suggests that actual HIV prevalence was 25% greater than revealed to Saughton's prison medical service. All 17 inmates who were HIV-1-antibody-positive on saliva testing had injected non-medically prescribed drugs. The high reported frequency by inmates of injecting in prison highlights the urgent requirement for drug reduction and rehabilitation programmes for injecting inmates. Linked anonymous voluntary HIV testing of saliva can provide valuable information about HIV prevalence for the planning of prison resources and policy. PMID- 1503692 TI - Inactivated polio vaccine hyperimmunization in adults with HIV disease: a placebo controlled study. PMID- 1503693 TI - HIV antigens detected in gingival fluid. PMID- 1503694 TI - Detecting HIV antibodies in needle-exchange syringes. PMID- 1503695 TI - Disseminated Rhodococcus equi infection initially presenting as foot mycetoma in an HIV-positive patient. PMID- 1503696 TI - Necrotizing enterocolitis in a patient with AIDS. PMID- 1503697 TI - Preventive tuberculosis chemotherapy in HIV infection: a priority for study. PMID- 1503698 TI - Candida krusei sepsis in HIV infection. PMID- 1503699 TI - Treatment of patients with advanced HIV infection and zidovudine intolerance with dideoxyinosine. PMID- 1503700 TI - Cranial Salmonella abscess with parietal bone osteomyelitis in an HIV-infected patient. PMID- 1503701 TI - Progression to AIDS in HIV-infected patients with oral candidiasis or hairy leukoplakia. PMID- 1503702 TI - [A drug evaluation and classification program in the USA--also a model for Germany]. AB - The question of recognition and possibilities of proof regarding impairment by narcotics and drugs is gaining significance also in Germany. Therefore, it is necessary to deal more closely with the United States "Drug Evaluation and Classification Program" and consider its application in Germany as well. The American program is based on standardized education of drug recognition expert trainees and well-tested methods of examination. The results are convincing. The expert reports prepared by the examiners and the chemical-toxicological results correlate in 80 to 97% of the cases. As long as no definite findings regarding dose/concentration effect relationships exist, the classification of behavior, appearance and medical examination plays a significant role. To a great extent, the program makes allowance for the existing possibilities in Germany as well. The authors of this article would consider it to be wrong if, in Germany extensive, time-consuming field studies were undertaken to obtain further knowledge prior to introduction of such a program. On the other hand, despite the existing difficulties, it should be endeavored to find dose/concentration effects. PMID- 1503704 TI - [Leaving the scene of an accident--a special offense in forensic psychiatric assessment?]. AB - A retrospective study on a hit-and-run group of drivers is reported. In comparison with a control group the study did not reveal special characteristics of these offenders. Mechanisms responsible for a driver leaving the place of a traffic accident are discussed. With reference to driver's escape psychogenic reactions and alcoholic intoxication often are observed, while (post-traumatic) twilight states and brief reactive psychosis are extremely rare events. Intensity of psychological disturbance during the offence may be assessed by criteria for evaluating responsibility of offenders with crimes of passion. PMID- 1503703 TI - [Effect of alcohol as a cause of fatal traffic accidents: are official figures correct?]. AB - Starting point is the question whether in the official records of fatal road accidents driving while intoxicated is adequately taken into account as a cause. A former investigation with accident data of 1976 yielded a considerable number of undetected and not registered cases. On the basis of the fatal road accidents of the Saarland region for the years 1988, 1989 and 1990 the former results could be confirmed on the whole. Only with 25 per cent of all persons involved in a fatal accident a breath or blood test for checking alcoholic impairment had been arranged. The assumption is well substantiated that the remaining 75 per cent include many impaired persons and that not only every fifth victim of traffic accidents is a result of alcoholic impairment but about 40 per cent. Proposals are made for getting in the future more reliable counts and a better basis for fighting against DWI-offences. PMID- 1503705 TI - [Long-term rehabilitation of alcohol dependent drivers (1)--individual psychologic traffic therapy]. AB - The "Individualpsychologische Verkehrstherapie (IVT-Ho)" is a rehabilitation measure for accident-prone drivers. In it are treated principally drivers who are problem drinkers, for whom the usual re-education is unsuitable because of severe alcohol problems. IVT comprises a psycho-therapeutic process, medical care and traffic re-education, and is tailored to individual problem situations respectively. A scientific study of the success rate indicates that through IVT, reductions of the probability of relapse are achievable, which far exceed even the effectiveness of re-education carried out with fewer problematical cases (e. g. Leer model). PMID- 1503706 TI - [Regulatory proposals concerning sterilization by means of ionizing radiation]. PMID- 1503707 TI - [Sterilization by gamma radiation of materials for pharmaceutical use: the problem of its effect on chemical structure]. PMID- 1503708 TI - [Concrete possibilities for sterilization of raw materials for pharmaceutical use with gamma rays]. PMID- 1503709 TI - [Sterilization of ophthalmic products with gamma rays]. PMID- 1503710 TI - [Description and confirmation of the process of gamma irradiation]. PMID- 1503711 TI - Vocal fold stripping. PMID- 1503712 TI - Stroboscopy and phonosurgery. PMID- 1503713 TI - Structured abstracts come to the Archives of Otolaryngology--Head and Neck Surgery. PMID- 1503714 TI - Management of the paralyzed face with microneurovascular free muscle transfer. AB - Facial paralysis is a devastating physical condition in which no single therapeutic approach consistently restores mimetic facial expression. The purpose of this article is to review the current treatment modalities for facial paralysis with particular emphasis on the indications for using free flaps to achieve facial reanimation. Primary attention is given toward rehabilitation of the lower two thirds of the face. The various neuromuscular free flaps used for facial reanimation are described and their merits and deficiencies are discussed. PMID- 1503715 TI - Complications and early outcome of anterior craniofacial resection. AB - OBJECTIVE: To evaluate the complications of anterior craniofacial resection and correlate their impact with tumor control status. DESIGN: We conducted a retrospective review of 32 consecutive, operable patients' records seen over a 6 year period, requiring 35 procedures. SETTING: Academic tertiary referral medical center. PARTICIPANTS: Twenty-six patients (81%) had malignant lesions (esthesioneuroblastoma, squamous cell carcinoma, and a group of miscellaneous malignant tumors). Six patients had various benign neoplasms. INTERVENTION: The surgical approach involved bifrontal craniotomy coupled with lateral rhinotomy in 19 cases (61%), facial degloving in 10 cases (32%), a total rhinectomy in one case, and endoscopic sinusectomy without facial incision in two cases. OUTCOME MEASURE: Clinically noted complications and oncologic outcome. RESULTS: There was one avoidable perioperative death indirectly associated with the patient's procedure. Nine patients suffered significant intracranial neurological complications such as tension pneumocephalus and delayed epidural abscess. All of these complications were managed successfully. Of patients with malignant tumors, 13 (52%) are alive with no evidence of disease and one is alive with recurrence after a mean follow-up period of 28.9 months. The 10 patients who succumbed to disease had a mean postoperative survival of 22.9 months. CONCLUSIONS: In contrast to the perspective of only a decade ago, we conclude that craniofacial resection is a relatively safe, versatile, and effective procedure for surgical management of tumors involving the anterior skull base. PMID- 1503716 TI - Accuracy of pathologic diagnosis in thyroid lesions. AB - Although there is much literature devoted to the role that fine-needle biopsy plays in the management of the thyroid mass, only a handful of studies deal with the diagnostic accuracy of the frozen section and final paraffin section of thyroid lesions. Fine-needle biopsy results, frozen-section diagnoses, final paraffin-section diagnoses, and panel review diagnoses were recorded for 137 consecutive patients who underwent thyroidectomy procedures. The overall accuracy of fine-needle biopsy, frozen-section, and paraffin-section diagnoses was 81%, 87%, and 94%, respectively. The high positive predictive value and specificity of both the fine-needle and frozen-section modalities suggests that intraoperative pathology consultation, given that the preoperative needle aspirate is positive for malignant neoplasia, can offer little further in the treatment of the patient. Statistical analysis of the accuracy of the three modalities suggests strategies for accurate treatment of the thyroid nodule. PMID- 1503717 TI - Pathological basis of surgery in the management of postradiotherapy cervical metastasis in nasopharyngeal carcinoma. AB - Radical neck dissection was performed on 43 patients with nasopharyngeal carcinoma in whom persistent or recurrent cervical metastasis developed after radiotherapy. The pathologic nature of the tumor in the cervical lymph nodes was studied with step serial sectioning of the entire radical neck dissection specimen at 3-mm intervals. In 70% of patients, more tumor-harboring lymph nodes were detected in the specimen when compared with clinical examination. The extensive behavior of the tumor in the cervical metastases was reflected by the presence of extracapsular spread in 70% of the lymph nodes and the existence of isolated clusters of tumor cells in 35% of the specimens studied. Tumor tissue lying in close proximity to the spinal accessory nerve was demonstrated in 27.5% of the specimens, and 72% of the tumor-bearing lymph nodes were located in the posterior triangle. Radical neck dissection is recommended as the salvage procedure for these patients. PMID- 1503718 TI - Experience with the modified pectoralis major myocutaneous flap. AB - Results of 75 reconstructions with a modified pectoralis major myocutaneous flap are described in patients with advanced (stages III and IV) head and neck tumors between 1982 and 1986. The course of the supplying thoracoacromial artery was determined with angiographic studies and was found to follow the middle clavicular line in most cases. The pectoralis major muscle was mobilized up to its acromial attachment, which made the bridging of considerable distances possible between the site of the removed tumor and the donor site. The bulk of the pedicle was reduced at the same time without endangering the safety of the blood supply of the pectoralis major myocutaneous flap. The flaps were viable in the 70 evaluable patients. Partial necroses were observed in three cases. Postoperative fistulas were encountered in 13 patients (surgical closure was necessary in three). Reconstruction with the pectoralis major myocutaneous flap is a safe and versatile procedure, yielding good clinical and functional results in patients with advanced head and neck tumors. PMID- 1503719 TI - Paranasal sinusitis associated with nasotracheal and orotracheal long-term intubation. AB - The impact of nasotracheal and orotracheal long-term intubation on the development of sinusitis paranasalis was investigated in a prospective study. Daily A-scan ultrasound examinations of the maxillary sinuses were performed on 44 intensive care unit patients (20 nasally, 24 orally intubated) who required prolonged intubation (greater than 24 hours). At the end of the investigation period 19 (95%) of 20 nasotracheally and 15 (63%) of 24 orotracheally intubated patients showed pathologic antral sinus findings. In nasally intubated patients the incidence of bilateral sinusitis was significantly higher and its onset sooner. Pathologic organisms were found in the sinus aspirates in seven of 13 nasotracheally intubated patients, but only in two of nine patients with an oral tube. Thus, the nasotracheal tube can be seen as an adding factor in the development of sinusitis paranasalis. PMID- 1503720 TI - Respiratory compromise after adenotonsillectomy in children with obstructive sleep apnea. AB - A retrospective study of pediatric patients with obstructive sleep apnea who underwent adenotonsillectomy between 1987 and 1990 was undertaken to determine the frequency of postoperative respiratory compromise and to determine if risk factors for its development could be identified. Sixty-nine patients less than 18 years old had polysomnographically documented obstructive sleep apnea and were observed postoperatively in the pediatric intensive care unit. Of these, 16 (23%) had severe respiratory compromise, defined as intermittent or continuous oxygen saturation of 70% or less, and/or hypercapnia, requiring intervention. Compared with patients without respiratory compromise, these patients were younger (3.4 +/ 4 vs 6.1 +/- 4 years) and had more obstructive events per hour of sleep on the polysomnogram (49 +/- 41 vs 19 +/- 30). They were more likely to weight less than the fifth percentile for age (odds ratio [OR], 5.1; 95% confidence interval [CI], 1.4 to 18.7), to have an abnormal electrocardiogram and/or echocardiogram (OR, 4.5; 95% CI, 1.3 to 15.1), and to have a craniofacial abnormality (OR, 6.2; 95% CI, 1.5 to 26). Multiple logistic regression analysis revealed the most significant risk factors were age below 3 years and an obstructive event index greater than 10. Children with obstructive sleep apnea are at risk for respiratory compromise following adenotonsillectomy; young age and severe sleep related upper airway obstruction significantly increase this risk. We recommend in-hospital postoperative monitoring for children undergoing adenotonsillectomy for obstructive sleep apnea. PMID- 1503721 TI - Histiocytosis X of the head and neck in a pediatric population. AB - Despite an extensive literature, histiocytosis X is still a poorly understood disease and the origin remains unknown. To study the impact of recent therapeutic and diagnostic advances on this disease, 28 cases of histiocytosis X treated at Children's Hospital of Los Angeles, Calif, from 1976 through 1987 were reviewed. A classification system was developed that accurately described the clinical outcome in our patients. Type patients (n = 7) had monostotic disease, and type 2 patients (n = 15) had multiple tissue sites other than the viscera. The latter type was further divided into types 2A and 2B, depending on whether lesions were solely osseous (type 2A [n = 8]) or if soft-tissue sites were involved (type 2B [n = 7]). Type 3 patients (n = 6) had disseminated disease at the time of presentation, as defined by visceral involvement other than the liver. Type 1 patients were usually treated by surgical curettage alone and had an excellent prognosis. Type 2A patients required either surgery or radiation for symptomatic lesions. Type 2B patients were treated similarly. In addition, Type 2B patients received chemotherapy, a practice that is intensively debated in the literature. All the Type 2 patients survived with varying morbidity. Type 3 patients were all treated with chemotherapy but none of them survived. The majority of patients with histiocytosis X had otolaryngologic manifestations ranging from bony lesions to infectious complications. To conclude, the term histiocytosis X should be maintained to describe a spectrum of diseases. A simple classification system with three divisions gives reliable prognostic and therapeutic guidelines. PMID- 1503722 TI - Side effects of repeated ototopical application of fosfomycin. An animal study. AB - In view of the possible role of fosfomycin in the topical treatment of chronic suppurative otitis media, the effects of this drug on inner ear function were investigated. Fosfomycin (20% aqueous solution) was applied repeatedly to the round window membrane of both ears of pigmented guinea pigs. Hearing thresholds were determined by daily frequency-specific evoked response audiometry with stimulation frequencies ranging from 1 to 32 kHz. Both positive (neomycin) and negative (saline) controls were included. Results were analyzed statistically. No significant and progressive hearing loss was found with fosfomycin. At 32 kHz, however, the hearing levels at the end of the test period were significantly worse in the fosfomycin group than in the saline group. PMID- 1503723 TI - Eyelid level after lower lid blepharoplasty with skin excision. The relationship of intraoperative and postoperative lid levels. AB - Sixty-seven consecutive patients (134 lids) undergoing lower lid blepharoplasty with skin excision had preoperative, intraoperative, and postoperative photographs taken in a sitting position. There was correlation between intraoperative and postoperative lower lid levels in 119 (89%) of 134 lids. There were nine lids with normal intraoperative lower lid level but postoperative lower lid retraction (scleral show). All nine of these lids had preoperative lower lid retraction. This demonstrated a high correlation between intraoperative and postoperative lower lid levels in the sitting position in lower lid blepharoplasty with skin excision, providing preoperative lower lid retraction is not present, horizontal lid laxity is corrected, and cicatricial lid retraction does not occur. PMID- 1503724 TI - Rigid endoscopy for the control of epistaxis. AB - Six individuals were selected to undergo rigid nasal endoscopy and electrocautery for treatment of refractory epistaxis. This intervention was successful in five cases, with no major complications. The procedure was found to be both cost effective and acceptable to the patient population. PMID- 1503725 TI - The first branchial cleft carcinoma. AB - Primary branchiogenic carcinoma was previously a debated entity. Initially it was a popular diagnosis for many cystic carcinomas of the neck. Then, in 1950, stringent criteria were defined for establishing the diagnosis of primary branchiogenic carcinoma. Only a limited number of cases have successfully fulfilled these criteria. We describe a patient who meets the criteria and who we believe represents the first reported case of a carcinoma arising from the vestigium of the first branchial cleft. We also review the literature on branchial cleft carcinomas and discuss the diagnosis, histopathologic features, and therapeutic options. PMID- 1503726 TI - Cholesteatoma of the maxillary sinus. AB - Cholesteatoma of the maxillary sinus, also known as keratoma, primary epidermoid tumor, epidermoid cyst, and keratocyst, is a rare entity, with a clinical presentation and radiologic findings that are difficult to distinguish from those of malignancy. We report a case of cholesteatoma of the maxillary antrum that occurred in a 12-year-old boy without any history of predisposing factors. Multiple theories of pathogenesis have been proposed throughout history; currently there are two accepted ones. We discuss these theories and present, along with the differential diagnosis, a review of the literature and the characteristic radiologic and pathologic findings. While it is a rare entity, the diagnosis of cholesteatoma should be considered for any slowly expanding lesion of the maxillary antrum. PMID- 1503727 TI - Bilobed flap reconstruction of the temporal forehead. AB - The temporal forehead is a particularly challenging area for reconstruction. Temporal forehead skin lies in a broad flat plane that varies in thickness. The eyebrow, scalp hairline, and lateral canthus comprise its aesthetic boundaries and limit the available tissue for repair of defects. Characteristically, skin tumors of the temporal forehead have extensive subclinical spread and their removal leaves large defects. The goal of temporal forehead reconstruction is to recreate the aesthetic boundaries of the forehead and to regain symmetry with the contralateral side. The temporal forehead bilobed flap is a single-stage procedure that takes advantage of the best color match of adjacent tissue and often allows primary closure of the donor sites in relaxed skin tension lines with minimal distortion. Several cases are presented for illustration of the technique. PMID- 1503728 TI - Preoperative thyroid scanning in presumed thyroglossal duct cysts. AB - The purpose of this study was to determine if preoperative thyroid scans are essential in the workup of presumed thyroglossal duct cysts. Questionnaires were sent to pediatric otolaryngologists and pediatric general surgeons with a 65% response rate. Fifty-seven percent of the physicians have encountered ectopic thyroid. In 58% of these, this was the only functioning thyroid tissue. Twenty eight percent of pediatric surgeons vs 65% of pediatric otolaryngologists routinely order scans. Two of the physicians encountering ectopic thyroid volunteered that they had successful litigation directed against them for removing the sole functioning thyroid and creating permanent hypothyroidism. There is a likelihood of encountering ectopic thyroid during the course of one's practice. A case of ectopic thyroid is presented, and management strategies are discussed. PMID- 1503729 TI - Congenital nasal pyriform aperture stenosis. Isolated abnormality vs developmental field defect. AB - Congenital nasal pyriform aperture stenosis has recently been described as a cause of nasal airway obstruction in the newborn. As some investigators have observed, the nasal pyriform aperture is narrowed owing to bony overgrowth of the nasal process of the maxilla. This overgrowth is confirmed by computed tomography. In six previously reported cases, follow-up as long as 16 months revealed normal facial growth. We describe six patients with congenital nasal pyriform aperture stenosis. On eruption of deciduous dentition, four of the six patients were found to have a single prominent central maxillary incisor, ie, "megaincisor." Computed tomographic scans have confirmed this dental anomaly as well as maxillary bony overgrowth. A single maxillary incisor has been described as an autosomal dominant microform of holoprosencephaly, a developmental field defect. We propose that in some patients congenital nasal pyriform aperture stenosis may represent more than an isolated congenital abnormality of the airway and may, in fact, be a midfacial dysostosis with associated endocrine and central nervous system abnormalities. PMID- 1503730 TI - Hereditary hemorrhagic telangiectasia. A new dermoplasty technique. AB - A new dermoplasty technique is described that allows both sides of the nasal septum to be covered with a single split-skin graft. This graft is designed with a narrow central dermal band that covers the septal dorsum and can be buried under the alar tissues. Exposure is obtained via a modified external rhinoplasty approach. The operation has been successfully performed on 11 patients, and in nine of them the graft take was complete. PMID- 1503731 TI - Paraganglioma of the inferior laryngeal paraganglia. A case report. AB - Laryngeal paragangliomas are uncommon, usually benign neoplasms. The overwhelming majority of these tumors are supraglottic, arising from the superior laryngeal parasympathetic paraganglia. Few paragangliomas of the infraglottic region have been described. We describe the case of a 35-year-old man with a family history of carotid body tumors who presented with an infraglottic paraganglioma. PMID- 1503732 TI - Pathologic quiz case 1. Basaloid-squamous carcinoma (BSC) of the larynx. PMID- 1503733 TI - Cytoplasmic and nuclear volume in the neurons of the spinal ganglia of the lizard: observation during hypertrophy. AB - It is known that neurons can undergo a process of hypertrophy when they are involved in an increase of the innervation field. This situation is easily observable in the spinal ganglia of the lizard which innervate the regenerated tail. Morphometric analysis carried out on the whole neuronal population of such ganglia has shown a greater increase of cytoplasmic volume with regard to the nuclear volume during hypertrophy (a decrease of the nucleo-plasmic index). Hypertrophy in the neurons of lizard spinal ganglia has been analysed both in still growing animals and in adults after amputation of the tail, showing analogous behaviour in the two situations. This suggests that the physiological growth of the animal does not influence the reaction to hypertrophy. PMID- 1503735 TI - [Presence of calretinin in neurons of the human intestine]. AB - Calcium-binding proteins are present in different neuron populations in the Central Nervous System. As concerns the Enteric Nervous System, only a few studies have been performed. In the present work we investigated immunohistochemically the localization of Calretinin in neurons of the human intestinal wall. Our results showed the presence of stained cell bodies and fibers with antibodies against Calretinin in the Auerbach plexus. Since most of the enteric neurons are characterized by a slow phase after hyperpolarization caused by Ca2+ dependent K+ channels, the role of Calretinin could be to modulate this particular electrophysiological behaviour. PMID- 1503734 TI - [Satellite cells of te dorsal root ganglia in neuronal hypertrophy]. AB - Amputation of the lizard tail is followed by its complete regeneration over a period of six-eight months. The new tail is innervated only by the last three pairs of spinal nerves upstream from the plane of amputation, since no nerve cells are present in the regenerated. The corresponding dorsal root ganglia increase in volume (hypertrophic ganglia) and most of their sensory neurons become hypertrophic. Satellite cells belonging to this hypertrophic ganglia increase in number. This paper describes an autoradiographic study, after administration of tritiated thymidine, of the hypertrophic dorsal root ganglia of the lizard during tail regeneration. We evaluated the number of satellite cells which neo-synthetize DNA ("labeling index = LI%) and are therefore suitable to undergo cell division. The LI% was significatively increased in hypertrophic ganglia when compared to internal control ganglia (not directly involved in the reinnervation process) and normal ganglia (lizards with intact tails). The comparison between internal control ganglia and normal ganglia showed higher LI% values in the formers, although this difference was not statistically significative. These results are in line with those obtained by other authors and suggest that satellite cells of dorsal root ganglia can undergo cellular proliferation also in the adult, especially in particular experimental conditions. PMID- 1503736 TI - Serum neuron-specific enolase in various pathological conditions. AB - Quantitative determination of neuron-specific enolase in the serum was performed by RIA method in 18 neurological patients and in 22 patients with pulmonary diseases. The data confirmed that the specificity of this marker is not absolute for the detection both of the nature and of the seat of origin of the disease. Further problems are posed in patients which simultaneously suffer from endocrine, nervous and pulmonary abnormality. PMID- 1503737 TI - Immunogenotypic characteristics of chronic lymphocytic leukemia patients from northern Italy. AB - Ig gene analysis, carried out in 25 patients failed to show rearrangement patterns typical of each stage, but, nevertheless, confirmed the monoclonal origin of leukemic cells in these patients. In addition, in 14 of them the pattern of Ig gene rearrangements measured on two different occasions was analyzed. Only in patients who had received chemotherapy, the intensity of the Ig germline band was greater than that of the rearranged bands, indicating the reduction of lymphocytosis after the therapy. Thus, though Ig gene rearrangement could not distinguish the CLL stage, our data confirm the usefulness, at all clinical stages, of Ig gene analysis as a tool in the evaluation of the efficiency of the therapy. PMID- 1503739 TI - Effect of N-2-acetylaminofluorene on poly(ADP-ribose) polymerase activity and DNA synthesis in cultured rat hepatocytes exposed to epidermal growth factor. AB - The nuclear enzyme poly(ADP-ribose) polymerase is involved in basic cellular processes such as DNA replication and repair, cell differentiation and transformation, gene expression. We have studied the effect of 2AAF, a genotoxic aromatic amine, on pADPRP activity during DNA synthesis stimulated by EGF, using the cultured rat hepatocytes model. DNA synthesis was measured as [3H]thymidine incorporated/microgram DNA while pADPRP activity was expressed in pmol[32P]NAD incorporated/min/microgram DNA. Our results show that 2AAF treatment of EGF stimulated rat hepatocytes induces a full block of DNA replication which is preceded and accompanied by a net inhibition of endogenous and total pADPRP activity, respectively. A block in pADPRP activity in normal hepatocytes, exposed to 2AAF in vitro or in vivo, could play a key role in cell transformation. Our data add further information on the possible involvement of this nuclear catalytic activity during DNA replication. PMID- 1503738 TI - A few remarks on the morphogenesis of the larynx. AB - After having reviewed the principal theories regarding the development of the larynx the authors performed a study on the morphogenesis of the above structure using four horizontally- and sagitally-sectioned human embryos. The conclusion of a study of these sections is that the LC constitutes the primordium of the laryngeal vestibule. From its lateral margin, caudally (Stage 19, Carnegie System), the primitive ventricles begin to form, while in the final stages the EL extends caudally enclosing a small cephalic infraglottic area and therefore completely separating the IG from the LC. Such findings in our opinion would confirm a different embryological derivation of the laryngeal cavity above and below the glottis. PMID- 1503740 TI - The extracellular matrix in slow-growing tumors of the central nervous system. AB - This report describes and illustrates the results of the histopathological and histochemical investigation on five slow-growing tumors of the central nervous system: four meningiomas and an ependymoma of the spinal cord. We have studied, by means of polarizing microscopy, sections stained with picro-sirius red F3BA that enhance the birefringence of collagen and reticulum fibres. The heterogeneous behaviour of the distribution of the collagen let us conclude that the fibrillar component of the extracellular matrix have a scarce importance for the speed of growth of these tumours. PMID- 1503741 TI - [Recall of the proper names of persons: effect of age and the modality of access]. AB - Aging is associated with phenomena of slowing down of cognitive processes and impairment of neuropsychological performances. Elderly people also report difficulty in the retrieval of proper names. Verbal fluency (VF) tests are particularly effective for the identification of even slight mental impairments. In this experiment we utilized the usual tests of VF for semantic categories and letters of the alphabet together with three new tests of VF for first names, differing in mode of access. The first mode was free recall, the second mode was semantic (first names beginning with a particular letter), and the third mode was autobiographical (first names of relatives). There were 3 experimental groups: young people with high education level, elderly people with high education level and elderly people with low education level. The aim of our work was to verify whether aging modifies the performance in the VF tests, particularly in the three first name VF tests. No difference was found between the groups of young and elderly people with high education level. The comparison between the two groups of elderly people, with high and low education level, showed that significant differences were present in some but not in all of the VF tests. While the two groups clearly differed in semantically oriented tests, no difference could be detected in the test oriented to episodic memory. This result seems to be inconsistent with the hypothesis that aging affects mainly episodic memory. PMID- 1503742 TI - [Hyperplasia of the intestinal smooth muscle tissue proximal to a partial surgical stenosis: an autoradiographic study]. AB - Hypertrophy of the smooth muscle wall of the rat small intestine occurs in the loops upstream from a partial surgical stenosis. This phenomenon is due both to cell hypertrophy and cell proliferation (hyperplasia). The thickness of the muscular layers reached its maximum after ten days from the intervention and then was maintained over the following days. Hyperplasia of the smooth muscle tissue has been demonstrated by means of autoradiography after administration of tritiated-thymidine. This investigation revealed the presence of 37%-44.5% of heavily labeled smooth muscle nuclei, index of active DNA neo-synthesis. On the contrary, no labeled nuclei were observed in the downstream tract as well as in the small intestine of the controls. These results, together with those obtained by other researchers, confirms that the smooth muscle tissue can undergo cell proliferation under particular conditions and that this phenomenon is often associated with the hypertrophic process. PMID- 1503743 TI - Enhanced sensitivity to G418 of human KB cells adapted to certain media and sera. AB - Sensitivity to the neomycin derivative G418 was determined for a human cell line, KB 3-1, that had been adapted to six different combinations of media and sera. The results indicate that while the plating efficiency is similar for all conditions, the susceptibility to G418 can differ markedly depending on the particular combination of media and sera used. This suggests that in experiments using neomycin resistance as a selectable marker, conditions may be found where the amount of G418 required for selection and maintenance of transfected cell lines can be reduced, providing a significant savings. PMID- 1503744 TI - Using proteases to avoid false identification of DNA-protein complexes in gel shift assays. AB - Gel mobility shift assays using crude nuclear extracts may result in the formation of multiple DNA-protein complexes reflected by their discrete gel mobilities. Identification of the multiple complexes can sometimes be complicated by the presence of protease activities in the extract as demonstrated here. We describe a simple protease-mediated partial digestion method that can be coupled with the gel shift assay to overcome the problem. The combined approach enables us to identify gel complexes that arise from protein degradation and therefore is suitable for analyzing those DNA-binding proteins exhibiting prominent protease sensitivity. The method should prove particularly informative in the search for tissue-specific complexes when crude extracts from different sources are compared by the gel shift assay. PMID- 1503745 TI - Direct PCR of washed blood cells. AB - We report a simple and rapid method for direct DNA amplification of washed blood cells by PCR. Small samples (2-100 microliters) of blood were washed, the cells resuspended in a buffer and used directly for PCR after boiling. Amplification of a specific DNA sequence of the human transthyretin gene, directed by the primers, was successfully performed. The method gives comparable results to amplifications made by purified DNA from blood. PMID- 1503746 TI - Measurement of protein in 20 seconds using a microwave BCA assay. PMID- 1503747 TI - Nitro-Block enhancement of AMPPD chemiluminescent signal in the detection of DNA. PMID- 1503748 TI - PCR amplification of GC-rich templates containing palindromic sequences using initial alkali denaturation. PMID- 1503749 TI - Electrophoresis gel buffer recirculator for under twenty dollars. PMID- 1503750 TI - A general, PCR-based method for single or combinatorial oligonucleotide-directed mutagenesis on pUC/M13 vectors. PMID- 1503751 TI - PCR screening of DNA cloned into polylinker-containing vectors with M13 sequencing primers. PMID- 1503752 TI - Rapid deprotection of synthetic oligonucleotides. PMID- 1503753 TI - A method for empirically optimizing the detection of DNA polymorphisms in genomic DNA by denaturing gradient gel electrophoresis. PMID- 1503754 TI - A simple treatment of serum for precise determination of recombinant factor IX in the culture media. PMID- 1503755 TI - Recombinant circle PCR and recombination PCR for site-specific mutagenesis without PCR product purification. AB - Two simple methods for site-specific mutagenesis are described and compared. In each method, the PCR is used in two separate amplifications to mutate the site of interest and to add ends to one PCR product that are homologous to the ends of the other PCR product. In the first method, the two products are combined, denatured and reannealed prior to transformation of E. coli in order to form recombinant circles in vitro, while in the second method, the two linear products are co-transfected directly into E. coli without prior manipulation, resulting in transformation of E. coli with the recombinant of interest by recombination in vivo. Each PCR amplification uses a plasmid template that has been linearized by restriction enzyme digestion outside the region to be amplified. This permits use of unpurified PCR products in these two protocols and generation of the mutant of interest with no other enzymatic manipulation in vitro apart from PCR amplification. In each protocol greater than or equal to 50% of the resulting clones contained the mutation of interest without detected errors. PMID- 1503756 TI - Use of a ligand-screening procedure to study the interaction of S. cerevisiae alpha 2 repressor with its operator sequence. AB - A simple and rapid screening procedure was developed to study the interaction of the S. cerevisiae alpha 2 repressor with its operator sequence. An E. coli expression vector was constructed in which the alpha 2 coding sequence was placed under control of the lac promoter. Bacterial colonies containing this vector could be lysed and assayed directly for binding of wild-type and mutant operator sequences when grown on nitrocellulose filters. alpha 2 assayed in this way showed the same sequence specificity as determined in vivo. Pools of mutant alpha 2 repressors in which the codons for Arg185 or Ser181 in the homeodomain region were randomized were created by cassette mutagenesis. These pools of mutants were screened with the wild-type operator sequence to determine allowed amino acid substitutions at each position. Results suggest that both Arg185 and Ser181 have a role in high affinity operator binding. PMID- 1503757 TI - Recombinant peptides as immunogens: a comparison of protocols for antisera production using the pGEX system. AB - Using an inducible vector system that directs high-level production and rapid purification of recombinant protein, we have immunized mice with peptides prepared by several methods: 1) samples fractionated by sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) subsequently transferred to PVDF membrane and subcutaneously implanted in mice; 2) samples cut directly from SDS PAGE gels and injected intraperitoneally; 3) injection of recombinant protein bound to agarose beads; and 4) injection of log-phase E. coli transformed with recombinant vector. All four strategies yielded specific antisera reacting with both the parental fusion protein and the recombinant fragment as determined by enzyme-linked immunosorbent assay and immunoblot analysis. Specific recognition of the recombinant fragment was demonstrated by a competitive inhibition assay in which the parental fusion protein abrogated reactivity of serum with the isolated recombinant fragment. PMID- 1503758 TI - Production of recombinant rat interleukin-6 in Escherichia coli using a novel highly efficient expression vector pGEX-3T. AB - Interleukin-6 (IL-6) is one of the most important mediators of the acute phase reaction in liver. For the production of recombinant rat IL-6 in Escherichia coli, a previously isolated cDNA coding for the rat IL-6 was cloned into the modified novel expression vector pGEX-3T. The IL-6 cDNA was highly expressed as a fusion protein with the glutathione S-transferase (GST) at its C-terminus and rat IL-6 at its N-terminus. The GST-IL-6 fusion protein was controlled by a tac promoter and could be induced very efficiently by isopropyl-beta-D thiogalactopyranoside. The synthesized GST-IL-6 fusion protein was insoluble and precipitated intracellularly in E. coli. Using an advanced technique, the insoluble protein was solubilized and purified to homogeneity by affinity chromatography using immobilized glutathione in a one-step procedure. PMID- 1503759 TI - Rapid separation of DNA molecules by agarose gel electrophoresis: use of a new agarose matrix and a survey of running buffer effects. AB - This report describes the use of a new type of agarose (FastLane agarose) for faster separation of DNA by agarose gel electrophoresis. DNA molecules separated in this agarose exhibited electrophoretic mobilities up to 30% higher than similar separations in standard analytical grade agarose. DNA molecules of all sizes examined showed higher mobilities in FastLane agarose. The mobility increase was predominantly due to the low electroendosmosis of FastLane agarose and was most pronounced in pulsed field gel electrophoresis separations. The magnitude of mobility increase varied depending on the conditions used for electrophoresis. PMID- 1503760 TI - A mechanically strong matrix for protein electrophoresis with enhanced silver staining properties. AB - Duracryl is a mechanically strong and elastic acrylamide-based matrix, useful for a wide variety of electrophoretic applications. The matrix is stable as a refrigerated solution for one year. Upon addition of appropriate catalysts, Duracryl forms a polymer-reinforced polyacrylamide gel matrix suitable for electrophoresis. The polymer-reinforced gel is superior to conventional polyacrylamide gels in terms of mechanical strength, elasticity and protein silver staining properties. Protein detection sensitivity by silver staining, as well as the linear response of silver deposition versus protein load, is equivalent to standard acrylamide/N,N'-methylene bisacrylamide gels. Additionally, the silver staining properties of the Duracryl matrix result in proteins appearing as monochromatic shades of grey instead of red, brown and yellow, as is the case of conventional polyacrylamide matrices. Monochromatic shades of grey are more suitable for image analysis and densitometry. The matrix is compatible with standard electroblotting and protein N-terminal sequencing procedures. Low acrylic acid content and conductivity allow incorporation of the matrix into isoelectric focusing gels. The matrix was found not to alter polypeptide migration relative to the standard acrylamide/N,N'-methylene bisacrylamide matrix. PMID- 1503761 TI - A simplified method for determination of specific DNA or RNA copy number using quantitative PCR and an automatic DNA sequencer. AB - Quantification of specific RNA or DNA molecules that are present in minute amounts in biological samples has previously been performed using PCR in the presence of an internal standard. We have adapted this concept by introducing several modifications that facilitate the quantification of the products and obviate the need for radioisotopes. After amplification, individual products are separated on sequencing gels and directly quantified using a fluorescent automated DNA sequencer. We describe two applications of this approach: the quantitation of minute amounts of bcr-abl hybrid mRNA from malignant cells and the determination of gene copy number in cells stably transfected with a plasmid bearing a chloramphenicol acetyltransferase gene. PMID- 1503762 TI - A two-step hybridization method for chemiluminescent detection of single copy genes. AB - We have developed a technique for the chemiluminescent detection of single copy genes that eliminates the high backgrounds and problems with probe labeling associated with existing methods. The procedure employs a primary hybridization of single-stranded probe DNA to immobilized target DNA, a secondary hybridization with a covalently cross-linked oligonucleotide-alkaline phosphatase conjugate, followed by incubation in the chemiluminescent substrate AMPPD and detection on x ray film. The key to the success of this method is that the primary probe contains a region complementary to the target DNA as well as to the oligonucleotide sequence of the secondary probe-alkaline phosphatase conjugate. Here we report our results using the two-step hybridization procedure to detect single copy genes from genomic Southern blots. PMID- 1503763 TI - A new approach to template purification for sequencing applications using paramagnetic particles. AB - A new method using traditional hybridization methodology, coupled with the new magnetic particle technology, has been developed for DNA purification, specifically for sequencing applications. The method is similar to the reverse hybridization blot system; however, a specific oligonucleotide probe was attached to the paramagnetic particle instead of a sheet membrane. The target DNA containing the complementary sequence of the probe hybridizes to the probe that is attached to the bead and is then magnetically removed from solution, washed and collected. This system eliminates the need of organic extractions and precipitation/concentration steps. The entire hybridization-purification system can be done in a 1.5-ml microcentrifuge tube making the method ideal for automation. M13 phage clones were purified with this method, both by manual means and by using the CATALYST 800 Molecular Biology LabStation fitted with a prototype magnetic station, and then sequenced. DNA sequencing results obtained with this system were reproducible and gave excellent length of read with low background. PMID- 1503764 TI - Use of a novel agarose gel-digesting enzyme for easy and rapid purification of PCR-amplified DNA for sequencing. AB - The use of a novel gel-digesting enzyme preparation provides an easy, rapid and convenient method to quantitatively recover PCR-amplified DNA from low melting point agarose gels. The PCR products purified using this method were readily sequenced and yielded good and unambiguous sequence data. PMID- 1503765 TI - A simple and efficient procedure for transformation of yeasts. PMID- 1503766 TI - An efficient procedure to dialyze volumes in the range of 10-200 microliters. PMID- 1503767 TI - Improved phenol-based method for the isolation of DNA fragments from low melting temperature agarose gels. PMID- 1503768 TI - A rapid and efficient method of subcloning into transformation vectors. PMID- 1503769 TI - Construction of a versatile set of retroviral vectors conferring hygromycin resistance. PMID- 1503770 TI - Efficient removal of hybridization signal from Southern blots probed with radio labeled oligonucleotides. PMID- 1503771 TI - A simple step to reduce background in E. coli transformations of blunt-ended plasmid ligation products. PMID- 1503772 TI - A rapid protocol for the introduction of large, multiple oligonucleotide-mediated insertions. PMID- 1503773 TI - Automated sequencing and mapping of cosmid DNA with fluorescently-labeled dideoxynucleotide terminators. AB - We have established a method for directly sequencing cosmid DNA on an automated DNA sequencer. The major advantage of this method is that only small amounts of cosmid template DNA are needed for the sequencing reactions. PMID- 1503774 TI - Double-stranded dideoxy sequencing from "dirty" DNA--done in a day. AB - A rapid method for preparing and directly sequencing plasmid and phagemid miniprep DNA is described. This protocol is a novel combination of two fairly standard procedures, resulting in quick and easy generation of sequence data. The lack of extensive manipulations in the purification process allows the production of DNA sequence data in a single day. PMID- 1503775 TI - A quick and inexpensive method for removing polysaccharides from plant genomic DNA. AB - A quick and inexpensive method has been demonstrated to remove polysaccharide contamination from plant DNA. Isolated plant genomic DNA with polysaccharide contaminants was dissolved in TE (10 mM Tris-HCl, pH 7.4, 1 mM EDTA) with NaCl ranging from 0.5-3.0 M, then precipitated with two volumes of ethanol. Most of the polysaccharides were removed effectively in a single high-salt precipitation at 1.0-2.5 M NaCl. At 3.0 M NaCl, the salt precipitated out of solution. Purified DNA was easily digested by either HindIII or EcoRI and was satisfactory as a template for PCR. The results show that high-salt precipitation effectively removed polysaccharides and their inhibitory effects on restriction enzyme and Taq polymerase activity. PMID- 1503776 TI - DNA cassettes containing the origin of transfer (oriT) of two broad-host-range transfer systems. AB - Plasmid constructs are described that carry retrievable DNA cassettes containing the origin of transfer region (oriT) from two broad-host-range plasmids. Restriction of these high copy number plasmids with any one of a variety of enzymes yields a linear DNA fragment of convenient size containing the oriT region of either pCUI or RK2. This DNA can be ligated into any vector or recombinant plasmid containing a compatible enzyme site and can be easily identified by size on an agarose gel. Any plasmid can therefore be mobilized using a number of helper strains or conjugative plasmids derived from the parental plasmids. In addition, the cassettes can be used for a variety of genetic manipulations including "selectable" linker mutagenesis. PMID- 1503777 TI - Magnesium-dependent thermostability of DNase I. AB - DNase I can be used to remove contaminating DNA from RNA samples. Heat treatment has been recommended as a method to inactivate DNase I enzymatic activity, thereby allowing subsequent reverse transcription and PCR amplification of DNase I treated RNA. We have found that inactivation of DNase I by heat treatment is strongly dependent on Mg2+ concentration. In addition, deoxyribonucleolytic activity of "inactivated" enzyme may be restored by changes in Mg2+ concentration following heat treatment. Caution should be exercised when using heat treatment alone as a method of DNase I inactivation. PMID- 1503778 TI - Cloning and direct sequencing of plant promoters using primer-adapter mediated PCR on DNA coupled to a magnetic solid phase. AB - A method that allows amplification and direct sequencing or cloning of an unknown DNA segment flanked by a known sequence is described using barley genomic DNA. The method avoids the step of circularization necessary for inverse PCR by ligation of primer-adapters to restricted genomic DNA. Specificity is achieved in the first amplification step; linear PCR with a biotinylated primer complementary to the known flanking sequence (primer 1-B) produces a single-stranded product that is purified employing streptavidin-coated magnetic beads. After this step, which removes genomic DNA, two rounds of exponential PCR are performed, first with the adapter-primer and primer 1 and second with primer 1 substituted by a nested primer 2. If the second primer is biotinylated, the product can be sequenced directly using solid-phase sequencing. We have employed this method to sequence directly and to clone the promoters of two late embryogenesis-abundant (Lea) genes (B19.4 and B19.3) from barley. Lea B19.4 and B19.3 encode putative desiccation-protective proteins that act in the final stages of embryogenesis and have previously been cloned as cDNAs. We demonstrate here that their proximal promoter regions are very similar (80% identity) and that both contain putative abscisic acid-responsive elements. PMID- 1503779 TI - Direct sequencing of baculovirus genomic DNA: sequence determination of the engineered respiratory syncytial virus chimeric FG gene. AB - Primer-directed enzymatic sequencing has proven to be an efficient and effective method for sequencing various size double-stranded DNA templates. We previously developed a primer-directed sequencing procedure for using double-stranded cosmid (50 kb) DNAs as template. We are interested in using this method to directly sequence larger DNA templates. Towards this goal we applied this method to directly sequence an engineered gene that had been transferred and integrated into the 130-kb baculovirus genome. Both crudely prepared and CsCl gradient banded baculovirus DNAs were tested and reasonable sequencing ladders were obtained for both types of DNA templates. As little as 3 micrograms of gradient banded baculovirus DNA were found to be sufficient to obtain film exposure times similar to those observed for cosmid size templates, 24 to 48 h. Effectiveness of the described method was demonstrated by obtaining the complete sequence of the engineered respiratory syncytial virus chimeric FG gene (2.5 kb in length) directly from the recombinant baculovirus "Baculo-FG" genome. Thus, our results demonstrate first, that double-stranded DNA templates as large as 130 kb can be sequenced directly and second, that the nucleotide sequence of engineered genes integrated within the baculovirus genome can be determined without the use of any intermediate steps of procedures. PMID- 1503780 TI - Localization of bFGF mRNA in cyclic rat ovary, diethylstilbesterol primed rat ovary, and cultured rat granulosa cells. AB - Evidence from in vitro studies strongly implicates basic fibroblast growth factor (bFGF) as a local regulator of ovarian function. However, the in vivo function of this growth factor in the ovary is uncertain. The objective of this study has thus been to investigate the biological role of bFGF in the rat ovary by monitoring bFGF gene expression using in situ hybridization in 3 systems; (1) the naturally cycling ovary, (2) ovaries of immature rats treated with diethylstilbesterol (DES), and (3) primary rat granulosa cell cultures. The rat estrus cycle can be divided into 4 stages as determined by vaginal cytology; diestrus, proestrus, estrus and metestrus. bFGF mRNA transcripts were localized to granulosa and theca cells of developing follicles during proestrus and estrus and in the corpus luteum following ovulation during metestrus. The estrogen analogue DES induced extensive in vivo folliculogenesis and high levels of bFGF mRNA in both granulosa and theca cells when compared to controls. Detectable levels of bFGF mRNA were also observed in primary granulosa cell cultures grown to high density. Employment of this in situ hybridization procedure has enabled the in vivo cellular sources of bFGF mRNA to be identified and the time course of expression during the estrus cycle to be monitored. The biological significance of this expression and the interplay between bFGF, extra- and intra-ovarian modulators are discussed. PMID- 1503781 TI - Inhibition of differentiation in a murine F9 embryonal carcinoma cell subline by leukemia inhibitory factor (LIF). AB - Leukemia inhibitory factor (LIF) is a cytokine previously shown to maintain pluripotent embryonic stem cells in their undifferentiated state. We have examined the effects of LIF in nullipotent embryonal carcinoma cell lines, and have found that LIF blocks differentiation induced by retinoic acid and at low temperature in OTF9 cells. LIF did not block differentiation in a parent F9 cell line. For OTF9 cells, LIF acts early in differentiation, inhibiting the appearance of parietal endoderm-type product cells. However, it acts subsequent to retinoic acid, and at least one early retinoic acid-induced event is unaltered in the presence of LIF. This finding provides both a means of dissecting the cascade of events leading to EC cell differentiation, and a well-characterised target cell type for studying the mechanism of action of LIF. PMID- 1503782 TI - Transforming growth factor e: amino acid analysis and partial amino acid sequence. AB - Our previous studies have demonstrated that transforming growth factor e (TGFe) acts as a mitogen for epithelial and fibroblastic cells in both monolayer and soft agar. We have also identified TGFe in both normal and neoplastic tissues of mostly epithelial origin, and in body fluids. In this study we report on the purification of TGFe to homogeneity from bovine kidney using a multistep purification protocol which utilizes high performance electrophoresis chromatography in the final step. Amino acid analysis of TGFe revealed high content of proline, aspartate and glutamate. Examination of partial amino acid sequence indicated no similarity to other, already characterized, growth factors. PMID- 1503783 TI - [Inquietude]. PMID- 1503784 TI - [Ibopamine in the treatment of congestive heart failure. Multicenter follow-up study]. AB - OBJECTIVE: To assess safety and efficacy of ibopamine, 200 mg TID, added to conventional treatment of congestive heart failure. DESIGN: A prospective, longterm, open study over two years (1986-88). A multicenter trial. SETTING: Outpatients of Departments of Internal Medicine of S. Francisco Xavier Hospital and Sta. Maria Hospital, and Departments of Cardiology of Sta. Cruz Hospital and Hospital Militar Principal, Lisbon. PATIENTS AND METHODOLOGY: 63 patients, 49 males from 34 to 80 years (m = 55.6 +/- 11.36) and 14 females from 41 to 80 years (m = 63 +/- 10.2), with congestive heart failure, NYHA class II in 52 patients (82.5%) and NYHA class III in 11 patients (17.5%) with a mean disease duration of 47.9 months entered into the study. Digoxin, diuretics, nitrates and antiarrhythmic drugs were allowed as concomitant therapy. Patients carried out clinical examination, ECG and laboratory tests monthly and X-Ray at the beginning and at the end of each year of the study. RESULTS: 42 patients completed one year of treatment and 20/42 continued for an additional year, 17 patients completed this second year of follow-up. From the 42 patients who completed the first year period, the NYHA class changed from II to I in 17/38 from II to III in 2/38 patients from III to II in 3/4 patients, and from III to IV in one patient. Twenty patients dropped during the first year of treatment. Six for non compliance (less than 80% of the treatment). Two were submitted to cardiac valve surgery. Seven had cardiovascular clinical events: one ventricular tachycardia, one atrial fibrillation, one pulmonary edema, one patient had no therapeutic effect, two patients had anxiety and fatigue and one patient died suddenly. One diabetic patient had uncontrolled hyperglycemia. One patient had gastric ulcer. Two had nausea and vomiting. Dysrhythmia and nausea and vomiting were the only clinical events, considered, respectively, possibly related and related, to ibopamine. During the second year of treatment 9/11 patients were stabilized in NYHA class I and 6/9 in NYHA class II, one patient changed from class II to class I, and one patient changed from class I to class II of the NYHA. Three patients did not complete the second year of treatment; one due to abnormal creatininemia; one for probable pulmonary embolism with CHF worsening; the third died suddenly. None of these events was considered related to ibopamine. Heart rate, arterial pressure, laboratory values and cardiothoracic index did not vary over the two years of the study. CONCLUSIONS: This has been the first study with data from patients treated with 200 mg TID of ibopamine during two years. Ibopamine has been shown to be a safe and useful drug added to conventional treatment of cardiac heart failure. Clinical events were few and well controlled after ibopamine interruption. PMID- 1503785 TI - [Evaluation of the aerobic capacity of blind people, by direct VO2 maximal measurement]. AB - Physical activity is the basic factor to the human being in order to assume his place in society. Blind persons are often sedentary, which compromises its physical capacity. The present work evaluates the blind person's physical capacity, analysing possible differences related to sex, age and life time blindness. The sample was constituted by 27 blind (congenital and noncongenital), 18 male and 9 female, aged between 17 and 37 years old. To evaluate previous physical activity, a questionnaire, was answered which showed a dominant sedentary population. The maximum oxygen uptake was determined in a treadmill test using standard procedures (Bruce protocol). Medium results for boys were 45.85 +/- 8 ml/kg/min and for girls were 34.46 +/- 3.8 ml/kg/min. The difference between congenital and acquired blindness on the VO2max values was 2.9 ml/kg/min, not statistically significant (p = 0.468). Those findings lead us to consider that aerobic capacity mostly depends on type and intensity of physical exercise which may be temporary related to the onset of blindness and visual impairment degree. PMID- 1503786 TI - [Changes in the physiologic pattern of mitral prosthesis regurgitation in the presence of a prosthetic dysfunction]. AB - AIM OF STUDY: Evaluation by transesophageal echocardiography of the effect on the characteristics of physiological regurgitant jets (JF) resulting from prosthetic disfunction due to pathologic regurgitation (JF). PATIENTS AND METHODS: We studied 69 consecutive patients with the diagnosis of prosthesis in mitral position using transesophageal echocardiography and color doppler codification. The patients were divided in two groups (N and D groups) according to the presence of prosthesis disfunction by pathologic regurgitation. In each patient we determined planimetric areas and atrial peak depth of each JF and also the sum of JF planimetric areas of each mitral prosthesis. When pathological regurgitation was present we calculated the highest planimetric area, severity degree and atrial peak depth in each JP. RESULTS: The planimetric area in each JF of group N was 330 +/- 167 mm2 and in group D 117 +/- 116 mm2 (p less than 0.001). The sum of the areas of JF in group N was 474 +/- 204 mm2 and in group D 254 +/- 176 mm2 (p less than 0.01). The atrial depth of JF in group was 32 +/- 15 mm and in group D 26 +/- 18 mm (p less than 0.01). In group D 29% of the patients had mild pathological regurgitation, 10% moderate and 61% severe. The maximum planimetric area of JP in group D was 1078 +/- 1007 mm2 with atrial depth of 37 +/- 28 mm. CONCLUSION: The pathological regurgitation in disfunction prosthesis in mitral position has a significant reduction effect in the dimension of prosthesis physiologic regurgitation jets. This transesophageal echocardiographic observation makes it possible to characterize and clarify more precisely the different types of mitral prosthesis jets. PMID- 1503787 TI - [Coronary atherosclerosis in acute myocardial infarct. Anatomic profile of diverse causes of death]. AB - OBJECTIVE: to study the degree of coronary obstruction by atherosclerotic plaques in a population dying with acute myocardial infarction. We defined subgroups by the degree of the obstructive lesion and compared the severity and distribution of coronary atherosclerotic lesions in different groups according to cause. STUDY DESIGN: systematic prospective study in patients dying in the acute phase of myocardial infarction in a University Hospital Coronary Unit during a four years period. POPULATION AND METHODS: we studied 193 patients corresponding 77% of the patients dead in the same period. 24 patients were excluded by technical reasons related to the preparation of necropsic material. The clinical protocol included 64 parameters and were considered the following causes of death: left ventricular failure (shock or acute pulmonary edema), left ventricular free wall rupture, interventricular septum rupture, primary asystole, pulmonary embolism and ventricular fibrillation. To study of the heart we performed the transverse slices technic after fixation; to study the epicardial coronary arteries we isolated the coronaries after fixation and made 5 mm transverse slices. The slices were macroscopic and microscopic evaluated for the degree of coronary obstruction in every 5 mm segment. We classified the degree of coronary obstruction in five grades: less than or equal to 25%; greater than 25% e less than or equal to 50%; greater than 50% e less than or equal to 75%; greater than 75% e less than 100%; and total obstruction. RESULTS: the degree of coronary obstruction in each epicardial segment were: Right ostium--grade I = 21%, grade II = 46%, grade III = 26%, grade IV = 7%, grade V = 0; Right coronary--grade I = 5%, grade II = 10%, grade III = 19%, grade IV = 28%, grade V = 38%; Left ostium- grade I = 27%, grade II = 50%, grade III = 19%, grade IV = 4%, grade V = 0; Left main--grade I = 16%, grade II = 43%, grade III = 28%, grade IV = 10%, grade V = 2%; Anterior descendent--grade I = 1%, grade II = 5%, grade III = 11%, grade IV = 34%, grade V = 49%; Left circumflex--grade I = 2%, grade II = 14%, grade III = 22%, grade IV = 40%, grade V = 22%. The number of coronary arteries with more than 75% obstruction for each group of one, two or three vessel disease were: 1 vessel--41 cases; 2 vessels--56 cases; 3 vessels--68 cases. The number of vessels with more than 75% obstruction for each cause of death were: Wall rupture--1 vessel = 20, 2 vessels = 18, 3 vessels = 11; Septum rupture--1 vessel = 0, 2 vessels = 2, 3 vessels = 2; Shock--1 vessel = 12, 2 vessels = 21, 3 vessels = 30; Acute pulmonary edema--1 vessel = 1, 2 vessels = 9, 3 vessels = 7; Asystole--1 vessel = 4, 2 vessels = 1, 3 vessels = 8; Pulmonary embolism--1 vessel = 2, 2 vessels = 5, 3 vessels = 8; Ventricular fibrillation--1 vessel = 2, 2 vessels = 0, 3 vessels = 2. CONCLUSION: in most patients dying with acute myocardial infarction, the coronary atherosclerotic lesions were present in two or three epicardial coronary arteries. The left anterior descendent artery was the more frequent artery with major lesion (greater than 75%). Major atherosclerotic lesion in just one vessel were more frequent in patients dying by cardiac rupture. PMID- 1503788 TI - [Effect of converting enzyme inhibitors in cardiac insufficiency mortality in the elderly]. AB - In a retrospective study we analyse two populations of aged patients in congestive heart failure, one treated with ACE inhibitors other not and the other with conventional therapy. Both populations received the same medication (diuretics and digitalis) and are equivalent in age, sex distribution, NYHA functional class and echocardiographic left ventricular parameters. Comparing the mortality of the two populations at the first, second and third year of follow up, a statistically significant reduction in mortality was found on the ACE inhibitors treated population, at the first year. However, this reduction did not reach statistical significance at second and third years. The results are similar to trials in which the effects of ACE inhibitors are studied on general populations in heart failure. PMID- 1503789 TI - [A case of incessant junctional tachycardia in a female patient with aneurysm of the interauricular septum]. AB - A permanent supraventricular tachycardia (SVT) was diagnosed in a 54-year-old hypertensive but cardiologically asymptomatic female patient, admitted to a surgery department for biliary lithiasis and hepatic echinococcosis. Heart rate was about 130 bpm and ECGs showed negative P waves in leads I, II, III, aVF, and precordial leads V2 to V6, being the RP' interval longer than P'R interval. Pharmacological intervention during Holter monitoring (20 hours) was instituted: following i.v. propranolol (4 mg), heart rate progressively decreased (to 112 bpm), mainly due to an increase in SVT RP' interval, and brief, spontaneous SVT interruptions occurred, preceded by P'R interval prolongation; SVT stopped after P' recording, and resumed after 2 sinus beats, (showing enlarged P waves and slightly prolonged PR interval), induced by cycle length shortening; later on, under i.v. amiodarone infusion (100 mg/hour) and coincident with the sleeping period, SVT cycle length progressively increased (to 600 msec), due to equivalent increases in P'R and R'P intervals. Two premature ventricular contractions (PVC) occurred during Holter monitoring at a coupling interval of 80-85% of SVT cycle length (480 msec): one PVC apparently originated in left ventricle lateral wall, captured the atria, which were activated 75 msec earlier than expected; the other PVC, apparently originated in left ventricle septoapical region, did not interfere with SVT cycle length. Before these data, a diagnosis of circus movement tachycardia, incorporating a concealed accessory pathway with slow retrograde conduction and ventricular insertion in the postoroseptal or left posterior paraseptal region, and showing minor impairment of antegrade AV nodal conduction, was made. Invasive electrophysiological study was then discarded. With combined oral antiarrhythmic therapy (amiodarone, 600 mg/d), plus propafenone, 450 mg/d), sinus rhythm was permanently restored, with evidence of intraatrial block, slightly prolonged PR interval and no preexcitation. Transesophageal echocardiography revealed a small atrial septal aneurysm associated with a small atrial septal defect; echocardiographic features were consistent with the hypothesis of incomplete regression of the atrial septal aneurysm after partial closure of the atrial septal defect. Abdominal surgery (cholecystectomy plus partial hepatic pericystectomy) was performed without any complications or SVT recurrences. During a 6-month follow-up period, maintaining amiodarone (200 mg/d) and propafenone (450 mg/d), the patient remained SVT-free, and Holter monitoring performed at 3 and 5 months showed permanent sinus rhythm and 1:1 AV conduction with slightly prolonged PR interval (less than 0.29 sec and shortening at faster heart rates). This case documents Holter monitoring capability for the evaluation of tachycardia mechanisms in patients with permanent SVT. PMID- 1503790 TI - [Civil aviation and cardiology. Admission rules and follow-up of the technical flying personnel of TAP-Air Portugal]. AB - The authors, based in European and American rules, consensus positions of Clinical Aerospace Congresses and their own experience, marked admission and follow-up rules of conduct for TAP Air Portugal aircrew. They stressed the importance of modern technology in arterial pressure ambulatory diagnosis and pointed the necessity of arterial pressure treatment in the other cardiovascular risk factors context. They relief ischemic myocardial disease because it is incompatible with flying safety, even in those submitted to coronary angioplasty or bypass graft surgery. For those with arrhythmias, valvular heart disease, myocarditis, cardiomyopathy and adult life congenital heart disease, we emphasize admission and follow-up rules. PMID- 1503791 TI - Magnetic resonance angiography (MRA) PMID- 1503792 TI - Physical principles and application of magnetic resonance angiography. AB - This paper reviews the physical principles of magnetic resonance angiography (MRA) acquisition methods, explains image presentation strategies for MRA, and discusses the advantages and disadvantages of various MRA methods. These methods include the time-of-flight, phase contrast, and black blood techniques. The essential goal of each of these flow imaging methods is to maximize signal differences between flowing and stationary tissues in order to provide morphological and physiological information. PMID- 1503793 TI - Approaches to diagnostic magnetic resonance carotid angiography. AB - MR angiography (MRA) by the time-of-flight technique has been very successful in the carotid arteries as a result of relatively rapid flow velocities and the availability of high sensitivity neck coils. Two-dimensional or three-dimensional acquisition through the carotid bifurcation is an effective screening technique whose accuracy is very competitive with Doppler ultrasound and whose anatomic detail rivals that of conventional contrast angiography. As methods are perfected for visualizing the entire carotid from the aortic arch to the circle of Willis, MRA will replace contrast angiography for many diagnostic applications. PMID- 1503794 TI - Magnetic resonance angiography in intracranial vascular disease. AB - Magnetic resonance angiography (MRA) offers a noninvasive alternative for studying normal and pathological blood vessels within the brain. Insights from important clinical aspects of intracranial vascular disease enable the effective application of MRA. Several MRA techniques have demonstrated clinical utility for the detection and characterization of intracranial vascular pathology. Clinical protocols should comprise combinations of time-of-flight and phase-contrast acquisitions to achieve diagnostic sensitivity. PMID- 1503795 TI - Cardiothoracic magnetic resonance angiography. AB - At the current state of the art, cardiothoracic MR angiography offers the clinician information that is supplemental to that provided by other noninvasive imaging techniques. Indeed, in some areas MR angiography will likely surpass currently used methods as the technique of choice. Specifically, measurement of cardiac output, pulmonary blood flow, and lung perfusion can be performed relatively accurately and simply during a brief MR examination. Both standard spin-echo and angiographic evaluation of the thoracic aorta provide qualitative images with superior resolution. Additionally, development of pulmonary artery angiography is progressing rapidly and may soon be clinically useful. Phase incoherence caused by complex flow and resulting in a signal void is useful for location and qualitative assessment of abnormal flow jets induced by stenoses. However, this phenomenon represents the major limitation to quantitative assessment of flow abnormalities. Methods to increase signal to noise and/or reduce phase incoherence must be developed before MR angiography can be used effectively to assess abnormal flow conditions. PMID- 1503797 TI - Prospects for the future: magnetic resonance fast scanning and flow quantitation. AB - High-speed scanning techniques are quickly emerging to provide new applications in the MRI domain. These potential applications range from the reduction of patient examination time to the functional imaging of human cognition. Additionally, flow quantitation is rapidly developing into a clinical diagnostic tool available for routine use. This article provides the concepts to acquire a rudimentary understanding of both topics. PMID- 1503796 TI - Magnetic resonance angiography of the lower extremity and renal arteries. AB - Magnetic resonance angiography (MRA) has been used to image the arteries to the lower extremities and to the kidneys, with promising initial results. In the case of the lower extremity arterial system, MRA provides a first opportunity to obtain anatomic images in a completely noninvasive fashion, including evaluation of the iliac and tibial vessels, to supplement the hemodynamic measurements that are a routine part of the preoperative evaluation. In the case of renal artery stenosis, MRA may soon become the initial screening modality of choice, especially in patients with renal insufficiency, in whom contrast scintigraphy may have limited accuracy and in whom contrast angiography is relatively contraindicated. PMID- 1503798 TI - The contribution of nutrition research to the control of undernutrition: the Indian experience. AB - Since diseases directly related to undernutrition are the major public health problems of India, nutrition research in the country has been largely directed towards elucidating their causes and identifying the most feasible methods for their prevention and control. This effort is an interdisciplinary exercise carried out in the laboratory, the clinic, and the field, with close interaction among biochemists, clinicians, and epidemiologists. Some of the identified solutions have found practical application; but, as in other areas of scientific endeavor, a gap exists between the acquisition of knowledge in the laboratories and its application in the field. Today, thanks to research efforts of the last few decades, we have the knowledge with which most diseases related to undernutrition can be prevented. Unfortunately, however, we do not always have the means of applying this knowledge under real-life conditions in the field. Even so, nutrition research during the last few decades has contributed significantly to the amelioration of undernutrition among poor communities in India. PMID- 1503799 TI - The influence of maternal nutrition on lactation. PMID- 1503800 TI - Dietary impact of food processing. PMID- 1503801 TI - Dietary carotenes, vitamin C, and vitamin E as protective antioxidants in human cancers. PMID- 1503802 TI - Retinoids and cancer prevention. AB - As indicated above, in some cases the effects of retinoids appear to be species specific. Although retinyl acetate and 4-HPR are ineffective in preventing mammary cancer induced by DMBA or occurring spontaneously in mice, these retinoids prevent carcinogen-induced mammary cancer in rats. In contrast, retinoids have modest chemopreventive activity for bladder cancer in various strains of both mice and rats and may have some therapeutic and preventive effects in human bladder. Retinyl palmitate is reported to reduce the incidence of esophageal lesions in hamsters; however, retinyl acetate may increase the incidence of esophageal tumors in rats. Although 13-cis-RA reduces the incidence of spontaneous thymic lymphomas in AKR mice and C57Bl/10W mice exposed to X rays and has some therapeutic effect on myelodysplastic syndromes in humans, 4-HPR may enhance leukemic progression in patients with this syndrome. For treatment of this syndrome, selection of the proper retinoid appears to be important. Topically applied retinyl palmitate reduces the incidence of cervical cancer in hamsters, and topically applied RA has a therapeutic effect on cervical dysplasia in humans. Retinamides have a modest chemopreventive effect against pancreatic cancer in rats dosed with azaserine; these compounds are reported both to increase and to decrease the incidence of pancreatic cancer in hamsters. Retinoids may, or may not, be carcinogen-specific in different species. Some are effective in preventing mammary cancer in rats, regardless of which carcinogen is used. Applied to mouse skin, retinoids are active with either DMBA or BP as the carcinogen and 12-tetradecanoyl phorbol-13-acetate (TPA) as the promoter. Nevertheless, retinoids are not effective in preventing skin papillomas and carcinomas caused by UV light. There is no comparable system for humans, although retinoids demonstrate activity against basal cell carcinomas, squamous cell carcinomas, and actinic keratoses on the skin of humans. Fewer bladder tumors develop in rats dosed with HO-BBN when they are put on diets containing certain retinoids, but those dosed with FANFT are not affected. Similarly, retinyl acetate is reported to be active against liver tumors induced by 3'-MeDAB but not against those induced by aflatoxin B1. In contrast, forestomach carcinomas induced in hamsters by either DMBA or BP are prevented by retinyl palmitate. The route of administration of retinoids may also be important.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1503803 TI - Nutrient transport pathways across the epithelium of the placenta. PMID- 1503804 TI - Cellular and molecular aspects of adipose tissue development. AB - Both in animals and humans, before or after birth, angiogenesis appears to be closely coordinated in time and space with the formation of fat cell clusters. Monobutyrin, a novel fat-specific angiogenesis factor, may play a role in this process. The potential to acquire new fat cells appears to be permanent throughout life in both animals and humans, as revealed by in vitro experiments. Considerable evidence now supports the view that BAT and WAT are distinct organs; in addition, the existence of distinct BAT precursor cells is demonstrated by their unique ability to express the UCP gene. In bovine and ovine, the transformation of BAT into WAT is strongly suggested by the rapid disappearance after birth of UCP from the various BAT depots. Despite the initial cell heterogeneity of the stromal-vascular fraction, cultured stromal-vascular cells of adipose tissue are adipose precursor cells that show varying capacities for replication and differentiation, according to age and fat depot. Studies of adipose cell differentiation in vitro correspond to the sequence: adipoblast (unipotential cells)----commitment preadipose cell (preadipocyte)----terminal differentiation immature adipose cell----terminal differentiation mature adipose cell (adipocyte). Cell commitment is triggered by growth arrest and characterized by the expression of early markers (A2COL6/pOb24; clone 5; LPL), whereas only terminal differentiation of preadipocytes requires the presence of various hormones. Multiple signaling pathways have been characterized and shown to cooperate in the process of terminal differentiation. The concept that adipose cells behave as secretory cells is now emerging from in vitro data, since secretion of various proteins (LPL, adipsin, CETP) and important metabolites (fatty acids, monobutyrin, androgens, estrogens, prostaglandins) takes place both constitutively and upon hormonal stimulation. This suggests that adipose tissue participates more directly than previously thought in metabolic activities and energy balance. PMID- 1503805 TI - The eosinophilia-myalgia syndrome and tryptophan. PMID- 1503806 TI - Nutritional questions relevant to space flight. PMID- 1503807 TI - Hyperhomocyst(e)inemia as a risk factor for occlusive vascular disease. PMID- 1503809 TI - Coordinated multisite regulation of cellular energy metabolism. PMID- 1503808 TI - Dietary impact on biliary lipids and gallstones. AB - Although dietary factors influence bile lithogenicity and gallstone formation, the main dietary effect appears to be indirect, depending on an interaction between caloric consumption and gender-specific aspects of lipoprotein metabolism. Excessive energy intake elicits its detrimental effect by altering lipoprotein and hepatic cholesterol metabolism in association with hyperinsulinemia. Factors, dietary and genetic, that favor elevated hepatic cholesterol synthesis and production of a bile acid profile in which chenodeoxycholic acid predominates appear to be associated with lithogenic bile. An inconsistent effect of dietary fat saturation on gallstones is that polyunsaturates possibly increase risk in men and decrease risk in women. Vegetable protein may reduce the risk of cholelithiasis. Whereas both the amount and type of dietary fiber influence cholesterol and bile lipid metabolism, specific associations between fiber and gallstones in humans remain elusive. PMID- 1503810 TI - Nutritional aspects of collagen metabolism. PMID- 1503811 TI - Vitamin A: physiological and biochemical processing. PMID- 1503812 TI - Serum cholesterol and cancer risk: an epidemiologic perspective. AB - This review has examined the evidence surrounding two questions: (a) Is having low serum cholesterol associated with increased risk of cancer? (b) Does reducing serum cholesterol increase the occurrence of cancer? Some elevated risk of cancer for males with low serum cholesterol levels has been noted: the median of the studies examined is consistent with a 30% increased risk. The answer for females is less clear. The median of the studies examined suggests no more than a 5-10% increased risk associated with having low serum cholesterol. However, the risk seems to depend strongly on whether females have a central or peripheral body fat pattern (54). The cancers most consistently associated with low serum cholesterol levels are those of the colon and lung in males, the cervix and breast (but only for females under 50 years of age) in females, and leukemia in both sexes. In contrast, high cholesterol levels have been linked with an increase in brain cancer. While immunologic, genetic, and dietary explanations have been offered to explain the association, it is difficult to support the idea that low serum cholesterol causes cancer in any direct manner. First, the findings themselves tend to be generally weak and somewhat inconsistent. Second, the strong influence of fat distribution in women suggests that a metabolic/hormonal basis underlies the association. One would not expect the results to differ by body fat pattern if the relationship were a causal one. Finally, if there were a direct causal role, one would expect populations with low serum cholesterol levels to have higher cancer rates. In China, counties with the lowest average plasma cholesterol levels have the lowest cancer rates (78). While this observation is open to a number of interpretations, it does not support the idea that low serum cholesterol is a tumor initiator. In aggregate, the trials of lipid-lowering interventions reviewed here show an increase in cancer occurrence (primarily mortality) of approximately 24% in the cholesterol-lowered groups. However, the post-trial experience has shown a comparative deficit of cancer occurrence in the experimental groups. Recent evidence indicates that products in the cholesterol biosynthetic pathway affect DNA replication and cell proliferation. These findings suggests a mechanism by which cholesterol lowering might accelerate the development of tumors already initiated. The data that have been reviewed in no way suggest that treatment of hypercholesterolemia should not be pursued. They do suggest the presence of a relatively small subpopulation in whom reduction of plasma cholesterol may lead to increased occurrence of cancer.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1503813 TI - Lipids in human milk and infant formulas. AB - About 50 metabolically important fatty acids can be identified in human milk. The extent of absorption of milk fatty acids varies considerably from infant to infant, particularly in pre-term infants, and requires more study. Human milk provides sufficient vitamins A and E for the term infant, but supplementation with vitamins D and K may be necessary. More research is needed on the amounts of the fat-soluble vitamins in human milk, the efficiency of transfer from mother to infant, the reasons for variation in different women, and the consequences to breast-fed infants of inadequate intake of vitamins D and K. Breast milk contains the PUFA needed by term infants who are able to synthesize the long-chain PUFA soon after birth. Pre-term infants fed formulae need supplementation with n3 and n6 long-chain PUFA, since formulas currently do not contain these acids. More work is needed to determine the requirements for n3 and n6 fatty acids, expressed as weights per kilogram. A larger data base using improved analytical procedures to study the nature and content of lipids in human milk is needed. The impact of maternal genetics and diet on fatty acids in milk should be studied, as well as the effect of maternal diet on eicosanoids secreted by the mammary gland. Information on the structure and function of the milk fat globule and its membrane is needed. Little is known about the effect of milk banking on milk lipids. The reader of this review will no doubt find other gaps in our knowledge of the lipid composition and nutritional value of milk that require additional investigation. PMID- 1503814 TI - Fat substitutes: a regulatory perspective. AB - Fat substitutes, in theory, may provide special health benefits to certain population segments. The most probable benefits are a reduction in total fat intake and a subsequent reduction in intake of calories from fat. Whether individuals who consume high intakes of fat substitutes that are partially or totally nondigestible also benefit from lower calorie intake on a long-term basis is unknown. It is likely that many individuals will compensate by increasing total food intake to maintain calorie intake. Consumption of fat substitutes presents nutrition problems. Those fat substitutes that are partially or totally nondigested may reduce the bioavailability of other nutrients. Similarly, fat substitutes may have adverse effects on normal gastrointestinal tract function or intestinal tract flora. Unlike other functional food additives, fat substitutes can make up a significant portion of the total diet. For this reason, traditional safety factors cannot be applied. Consequently, more reliance on data from clinical studies involving human subjects and requirements for postmarket surveillance will be necessary as part of the approval process. PMID- 1503815 TI - Regulation of enzymes of urea and arginine synthesis. PMID- 1503816 TI - Intracellular immunization: trans-dominant mutants of HIV gene products as tools for the study and interruption of viral replication. PMID- 1503817 TI - The immunology of HIV infection: implications for therapy. AB - It is known that antiretroviral drugs can induce immunologic improvement in patients with acquired immunodeficiency syndrome (AIDS) and other manifestations of HIV infection. However, the improvements so attained are often partial and transient. This may result from a number of factors, including incomplete inhibition of human immunodeficiency virus (HIV) replication by available agents, the development of viral drug resistance, the effect of cytokines, or thymic damage. An understanding of this problem may be important in further development of AIDS therapies. It will also be important to learn how to best assess the response to various therapies. In this regard, the CD4 count is evolving as a mortality risk indicator in AIDS and as such may find utility in assessing new therapeutic approaches. We have observed that in a cohort of gay men receiving antiretroviral therapy in a research environment, nearly all deaths occurred in individuals with fewer than 50 CD4 cells/mm3. However, the relationship between the CD4 count and the hazard of dying may be influenced by a number of factors (e.g., active intravenous drug use, extreme poverty, etc.), and further studies are needed to define the relationship between CD4 and clinical endpoints under a variety of conditions. PMID- 1503818 TI - Potential use of immunoconjugates for AIDS therapy. AB - More than a dozen of hybrid proteins possessing reactivity with human immunodeficiency virus-type 1-(HIV-1) infected cells and cytotoxicity have been produced and studied by several groups. These proteins are prepared either by chemical cross-linking of a toxin and a carrier molecule or by expressing fused genes of the two moieties. These cytotoxic agents have been investigated to eliminate HIV-1-infected cells in vitro. The ID50 of these agents range from pM to nM. This article compares the results of the various approaches and discusses the limits and potential of immunoconjugates for AIDS therapy. PMID- 1503819 TI - HIV-specific vaccine therapy: concepts, status, and future directions. PMID- 1503820 TI - HIV drug resistance. PMID- 1503821 TI - HIV gp120 epitope immunodominance in MRL/Ipr mice. PMID- 1503822 TI - Localized conformational changes in the N-terminal domain of CD4 identified in competitive binding assay of monoclonal antibodies and HIV-1 envelope glycoprotein. AB - The CD4 antigen is established as a major cellular receptor for the human immunodeficiency virus (HIV). Previous studies have suggested that certain anti CD4 monoclonal antibodies (MAbs) can inhibit or enhance the binding of the viral envelope glycoprotein gp120 to CD4 by allosteric effects. In the study reported here, 17 anti-CD4 MAbs were tested for their ability to influence the binding of each other to recombinant soluble CD4 in a solid-phase radioimmunoassay. Marked enhancement of binding between specific pairs of MAbs was seen, as well as inhibition or lack of interaction. Enhancement was seen less often when CD4+ cells were used as the target antigen. Information on patterns of enhancement and inhibition permitted grouping of MAbs on the basis of epitope specificity, and this grouping was in agreement with published findings based on X-ray crystallographic studies. These results demonstrate connectivity between epitopes in the first domain of recombinant CD4 and suggest a high degree of flexibility of surface structure. These findings may be of physiological significance both in the normal function of CD4 and in the interaction of CD4 with HIV. The data have implications for research or therapeutic strategies based on recombinant CD4 or CD4 mutants and highlight the problems of interpreting experimental findings based on abrogation of MAb binding. PMID- 1503823 TI - Anti-CD4 anti-idiotype antibodies in volunteers immunized with rgp160 of HIV-1 or infected with HIV-1. AB - We examined the sera of volunteers vaccinated with recombinant gp160 of human immunodeficiency virus type 1 (HIV-1) and control volunteers for the presence of anti-(anti-gp160 idiotype) antibodies which antigenically mimic gp160 and, therefore, bind to CD4 on human cells. Anti-CD4 antibodies were detected in the sera of 3 of 5 rgp160 recipients and 1 of 5 controls by indirect immunofluorescence using CD4-transfected HeLa cells or enzyme-linked immunosorbent assay (ELISA) using recombinant soluble CD4 as the solid phase. The control volunteer who was positive subsequently developed antibodies to HIV-1 by Western blot analysis. The anti-CD4 antibodies detected in the sera of the rgp160 vaccinees and the control volunteer appeared to be anti-idiotypic in nature, reacting with a paratope expressed on goat anti-gp160 antibodies but not on antibodies from normal goat serum. Binding to either transfected CD4+ HeLa cells or blotted anti-gp160 serum could be inhibited by preincubating the anti-CD4 serum with soluble CD4, or preincubating the cells or blotted anti-gp160 serum with recombinant gp160. Anti-CD4 antibodies were initially detectable only after the antibody response to gp160 began to decrease in the vaccinees, and the HIV-1 infected volunteer mounted a detectable anti-HIV-1 antibody response only after a decline in the anti-CD4 antibodies in his serum. These data strongly suggest that anti-CD4 antibodies which are anti-idiotypic to a paratope expressed on anti gp160 antibodies are generated in response to both vaccination with rgp160 and infection with HIV-1.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1503824 TI - High-titer HIV-1 neutralizing antibody response of rhesus macaques to gp160 and env peptides. AB - Three groups of four rhesus macaques were immunized twice, one month apart with purified recombinant HIV-1LAI gp160 in the presence of either alum, incomplete Freund's adjuvant (IFA), or SAF-1. Two months later, the animals were injected twice again with a synthetic peptide with the sequence of the principal neutralization determinant (PND) of the HIV-1LAI isolate mixed with the same adjuvants. All animals received a booster injection of gp160 and PND peptide at 6 months. This regimen of immunization induced in the SAF-1 and IFA groups a high titer neutralizing antibody response that declined progressively over the course of the following 6 months. In contrast, only a weak response was observed in the alum group. Neutralizing antibody titers varied as anti-PND titers, suggesting that they were principally targeted to the PND. A shortened immunization protocol comprising two injections of gp160 at 0 and 1 month followed by one injection of PND peptide at 3 months is suggested as optimal for the induction of high titers of HIV-1 neutralizing antibodies in primates. PMID- 1503825 TI - Lack of autologous neutralizing antibodies in the cerebrospinal fluid of HIV-1 infected individuals. AB - The cerebrospinal fluids (CSF) and sera from HIV-1-infected individuals at different clinical stages were monitored for neutralizing activity against CSF derived HIV-1 isolates. None of the CSF samples and only one of seven serum samples could neutralize the autologous CSF isolate. CSF samples collected one to two years later from the same patients also lacked autologous neutralizing antibodies against these isolates. However, some CSF samples were able to neutralize heterologous CSF isolates albeit in low titers. HIV antibody positive control sera could readily neutralize all of the CSF isolates demonstrating that these isolates were not resistant to neutralization per se. IgG antibodies against the HIV-1 envelope protein and, specifically, against the V3 loop of HIV 1 gp120 (MN) were present in some CSF samples, although the samples lacked neutralizing activity. In summary, this study demonstrates a lack of autologous neutralizing antibodies in CSF samples when assayed against CSF-derived HIV-1 isolates. PMID- 1503826 TI - Molecular clones from a non-acutely pathogenic derivative of SIVsmmPBj14: characterization and comparison to acutely pathogenic clones. AB - Molecularly cloned simian immunodeficiency viruses capable of inducing acute, fatal disease in pig-tailed macaques had been derived previously from a biological clone (bcl-3) of the PBj14 isolate of SIV from sooty mangabey monkeys (SIVsmmPBj14). The present study was undertaken in order to characterize virus from a second biological clone of SIVsmmPBj14, bcl-1, which fails to induce acute or fatal disease. Polymerase chain reaction was used to amplify 5' and 3' viral genome halves. The DNA sequence of two 3' halves was determined, and an infectious recombinant generated using a bcl-3-derived 5' half and a bcl-1 derived 3' half. Overall, bcl-1- and bcl-3-derived viruses displayed close homology, differing by a total of 2% at the DNA level and 1-6% at the amino acid level within the 8 open reading frames examined. In contrast to the bcl-3-derived viruses, the bcl-1-derived viruses encode a truncated transmembrane envelope glycoprotein. Another consistent difference was the presence of a 22 bp duplication in the U3 portion of the long terminal repeat (LTR) of bcl-3-derived viruses that includes the NF-kappa B transcriptional enhancer binding site. To assess the importance of this duplication, virus chimeras were generated which removed the duplication from the 3'-LTR or from both LTRs of a bcl-3 clone. The former virus was unstable, reacquiring the duplication through recombination with the 5' LTR. No consistent difference were observed, however, between viruses with or without the duplication in the in vitro studies conducted to date.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1503827 TI - A caution on the use of SIV/HIV gag antigen detection systems in neutralization assays. PMID- 1503829 TI - Clinical therapeutics in HIV disease. PMID- 1503828 TI - Differences in neutralization of simian lentivirus (SIVMAC) in lymphocyte and macrophage cultures. AB - Comparison of neutralization of SIVmac251 in primary macrophage cultures with neutralization in lymphocytes (CEM174 cells) showed that neutralizing antibodies induced by SIV251 in infected rhesus macaques protected both macrophages and T lymphocytes against infection when the virus was preincubated with the antibodies. In macrophages, the neutralizing antibodies also protected against infection when added 1 hour after the virus. Addition of antisera to macrophages between 24 and 48 hours after virus inoculation resulted in infection with continuous release of small amounts of p24 into the supernatant fluids but these antibody-treated cultures failed to exhibit cytopathic virus replication. In contrast, the same neutralizing antisera did not protect lymphocytes against infection and subsequent cytopathic replication of the virus when added only 1 hour after virus inoculation. This distinction in the effect that neutralizing antibodies had on the development of cytopathic infection in lymphocytes and macrophages when added after virus inoculation, suggests that they could alter the dynamics of virus replication and therefore the pathogenesis of disease. PMID- 1503830 TI - Insights into HIV chemotherapy. PMID- 1503831 TI - Application of latent HIV-1 infected cellular models to therapeutic intervention. AB - The 10-year period of clinical latency following infection with the human immunodeficiency virus type-1 remains as a tremendous opportunity for therapeutic intervention. To decipher the viral and cellular mechanisms involved in controlling active and nonproductive viral expression, chronically infected cell lines have been developed which mimic in vivo latency at a cellular level. This review compares these models of chronic infection, emphasizing the advantages and limitations of this approach to the understanding of AIDS progression. In addition, it accentuates the utility of these models of chronic infection in the development and testing of novel drugs aimed at altering the efferent component of the HIV--1 life cycle. It is this component of the viral life cycle that has remained largely unexplored and open to novel therapeutic strategies for the prevention of lethal immunosuppression. PMID- 1503832 TI - Transmission of HIV to dental patients: more data. PMID- 1503833 TI - 'Odontogenic keratocyst in an infant'. PMID- 1503834 TI - A shot in the dark. PMID- 1503835 TI - Alternative management of a crown root fractured tooth in a child. AB - A crown root fracture of a tooth in a young person may necessitate the removal of the root and the placement of a space-maintaining partial denture followed by provision of a bridge. A case is reported of an alternative approach to treatment, in which the root fragment is retained in situ until the end of the pubertal growth spurt, in order to preserve alveolar bone, following which it is removed and replaced by an implant. PMID- 1503836 TI - An iatrogenic foreign body (dental bur) in the maxillary antrum: a report of two cases. AB - Two cases of foreign bodies of the antrum are reported. One was a turbine bur which presumably entered through an oro-antral fistula after a tooth extraction. The other was also a turbine bur where the mode of entry was not clear (lack of oro-antral fistula), but it presumably entered through the socket of the extracted tooth. The mucosa of the antrum appeared normal in spite of the lengthy presence of the foreign body. PMID- 1503837 TI - The clinical use of ITI transmucosal implants. AB - The ITI implant system has a background of research and development of over 15 years. It is distinctive in that the implant fixtures are transmucosal from the time of placement, requiring only a single stage in surgical treatment. In a relatively simplified approach to prosthetic management, standard overdenture components and conventional fixed partial denture techniques are used. In this report the assessment, surgical treatment and post-operative management of patients using ITI Bonefit implants are described and early results from 168 consecutive fixtures placed over a period of 3 years indicated. PMID- 1503838 TI - Arterial embolisation of a facial haemangioma. AB - Non-invasive investigations in the diagnosis of highly vascular lesions are without doubt a sound principle. A case is presented however, in which the clinical diagnosis of a haemangioma was confirmed by ultrasound and magnetic resonance imaging (MRI) but required further investigation by angiography to facilitate treatment. Embolisation is a well established technique available in most large radiology departments, but may not be well known by general dental practitioners. PMID- 1503840 TI - Tooth with a mission on a mercy ship. PMID- 1503839 TI - The check record in NHS practice. AB - Incorrect occlusion is a major cause of complete denture failure. Any technique which has the potential to solve this problem and consequently limit the number of review appointments must be worthy of consideration. The pre-occlusal or precentric check record is an accurate method of verifying the occlusion of complete dentures. Although the check record is taught in many teaching hospitals, it is not widely used in general practice. This is primarily due to the time-consuming nature of the conventional method. A variation on the standard technique is described, which is designed specifically for NHS complete denture practice. The materials used are inexpensive and the procedure takes approximately 10 minutes. PMID- 1503841 TI - Contributing factors and symptoms of stress in dental practice. PMID- 1503843 TI - Who is in control? PMID- 1503842 TI - Changes in dental health and dental practice. PMID- 1503844 TI - The cost of keeping one's hands clean. AB - After reading 'A Practical Gloving and Handwashing Regimen for Dental Practice' (Field E A, Jedynakiewicz N M, King C M. A Practical Gloving and Handwashing Regimen for Dental Practice. Br Dent J 1992; 172: 111-113), I undertook to do some simple research into the economics of glove wearing for the general dental practitioner based on the regimens mentioned in the article. The conclusion which I reached is that one not only needs to take into account the cost of the gloves but also the valuable surgery time taken in the washing of one's hands and gloves. The most cost-effective method of hand and glove washing was found to be the use of a single non-sterile glove with Hibisol. PMID- 1503845 TI - 'Audit in primary dental care'. PMID- 1503846 TI - 'Is there anybody out there?'. PMID- 1503847 TI - Cross-infection prevention. PMID- 1503848 TI - Psychological factors in oral lichen planus. PMID- 1503849 TI - A preliminary report on the effect of storage in water on the properties of commercial light-cured glass-ionomer cements. AB - Two commercially available light-curable glass-ionomer cements, Vitrebond and XR Ionomer, have been studied and their compressive strengths measured following storage under wet and dry conditions for varying lengths of time up to 3 months. The strongest cements were those stored in air and allowed to age. On the other hand, cements that were stored in water were found to become progressively weaker with time. Their failure mode was different from that of cements stored in air in that specimens became barrel-shaped as they were loaded and exhibited considerable plastic deformation prior to fracturing. By contrast, air-stored specimens behaved as predominantly brittle materials, the specimens essentially maintaining their integrity up to the point of catastrophic failure. Both of these findings indicate that the properties of these particular light-cured cements change markedly on exposure to moisture, a fact which is of clinical significance. PMID- 1503850 TI - Revising, reformatting and reforming the health-care system. PMID- 1503851 TI - Managing the cognitive enterprise: a new leadership paradigm for nurse executives. PMID- 1503852 TI - Mentoring in nursing administration. PMID- 1503853 TI - Application of antibody-mediated extraction for the stereoselective determination of the active metabolite of loxoprofen in human and rat plasma. AB - Antibody-mediated extraction followed by chiral high-performance liquid chromatography (HPLC) was applied to stereoselective determination in human and rat plasma of the active metabolite [(2S,1'R,2'S)-trans-alcohol] with three chiral centers of Loxoprofen, a 2-arylpropionic acid antiinflammatory agent after oral administration. Antiserum against the (1'R,2'S)-cyclopentanol moiety was obtained from a rabbit immunized with bovine serum albumin conjugate linked to the propionic acid moiety, in which another chiral center is located. Then, the immunoglobulin G purified by a protein A column was coupled to BrCN-activated Sepharose 4B. Plasma samples were applied to the immobilized antibody column. After washing the column to remove unrequired stereoisomers, a mixture of two diastereomers whose configurations were 1'R,2'S in the cyclopentanol moiety was extracted with 95% methanol. The solvent was evaporated and the residue was derivatized with (+)-(R)-1-(1-naphthyl)ethylamine as a chiral reagent to separate the diastereomers by HPLC. This combined analytical method showed the stereoselective metabolism of Loxoprofen in human, that is, 64% of the total amount of four trans-alcohol stereoisomers was in the 2S,1'R,2'S form, which is the active metabolite. This phenomenon was also observed in rats given Loxoprofen and its (2S)- and (2R)-isomers, and is explained by stereoselective ketone reduction of Loxoprofen to the (1'R,2'S)-trans-alcohol and inversion from 2R to 2S in the propionic acid moiety. Antibody-mediated extraction should be a selective and simple clean-up method for determining haptens with complicated structures, combined with an appropriate analytical method. PMID- 1503854 TI - [Cantrell's pentalogy: complete treatment, step by step]. AB - Since MAYOR and CANTRELL described in 1953 and in 1958 the ectopia cordis associated to other four anomalies, few cases have been reported, and only a small part of them have survived. We report the case of a neonate who presented with the features of the pentalogy. On the 3rd day we found at operation the heart laying over the left hepatic lobe, no pericardium could be identified and diaphragm was absent at its anterior edge. We made an "isolating sac" with duramadre fixed to the anterior thoracic wall, to both sides and to the posterior diaphragmatic defect. The initial management of the ventral defect is described. At the age of two years we initiated the definitive treatment aiming to: 1. To protect the heart. 2. To correct the huge abdominal eventration following the closure of the omphalocele. We described in details the technic employed to cover the precordial defect, to reconstruct the diaphragm, and finally as we treated in three consecutives stages the huge abdominal eventration. PMID- 1503855 TI - [Pyknodysostosis: extreme cause of sleep apnea]. AB - We describe a twentieth month old infant who had a pycnodysostosis syndrome. This malformation shows a loss of the normal mandible angle with generalized bone hyperdensification. The first produced and airway obstruction, with special relevance during sleeping hours. A polysomnography revealed an obstructive sleep apnea syndrome. The respiratory picture deteriorated with worsening of the airway obstruction, hypoxemia and finally pulmonary hypertension and cor pulmonale. A tracheostomy was performed, with resolution of the sleep apnea and pulmonary hypertension. The etiology, pathophysiologic consequences and surgical treatment of obstructive sleep apnea syndrome is reviewed. PMID- 1503857 TI - [If it is not negligence, what can it be called]. PMID- 1503856 TI - [Superficial cutaneous nevus lipomatosus of Hoffmann-Zurhelle. Report of a case]. AB - Nevus lipomatosus cutaneous superficialis is a rare idiopathic abnormality characterized by ectopic adipose tissue in the dermis. We present a typical case, making reference to the main clinical characteristics, histological peculiarities, pathogenical hypothesis and treatment of this tumor. PMID- 1503858 TI - [Hirschsprung disease]. PMID- 1503859 TI - [Intestinal neuronal dysplasia]. AB - Neuronal intestinal dysplasia and hypogenesis of the submucous plexus, frequent cause of constipation in infancy and childhood. PMID- 1503860 TI - [Manometric study in the newborn]. AB - Hirschsprung's disease in the newborn period has a bad prognosis due to the high mortality rate caused mainly by enterocolitis. It has been shown that the incidence of enterocolitis diminishes with the precocity with which diagnosis is made. All diagnostic methods have problems in the neonate. We intent to investigate the anorrectal manometry in the neonate using a probe devised and built by us. The hypothesis we try to prove is that the rectoanal reflex is present in all newborn, having no relation with age, length of gestation period, nor weight. The characteristics of the probes used allowed long recording sessions without any sedation of patients. The validity of this technique is unquestionable from the view of the reliability of the recordings independently of the weight, gestational age and birth age of the infants. PMID- 1503861 TI - [Intraoperative histochemical diagnosis of Hirschsprung disease]. PMID- 1503862 TI - [Total colonic aganglionosis]. AB - Between 1966 and 1990, 171 cases of Hirschsprung's disease, of which 21 were total colonic aganglionosis, were surgically treated at our centre. In the first period up to 1978, in which total parenteral nutrition (TPN) was not used, six of 11 patients died. From 1979 to 1990, ten further cases were treated with the support of TPN and only one death occurred, in a child with aganglionosis up to one-half of the yeyunum. The 14 surviving patients were treated, ten with the Duhamel technique, two with Rehbein and one with Boley procedure. The Lester Martin technique was not used. Follow-up of ten of then patients showed their good general condition. The number of daily bowel movements, on the average three, was higher than normal. Studies of serum iron, vitamin B12 and folic acid absorption showed slightly low values, which require close monitoring. Hydrogen and fecal test were normal. PMID- 1503863 TI - [Mechanical sutures]. PMID- 1503864 TI - [Diagnosis and treatment of Hirschsprung disease in Spain in 1990. Results of a multicentric survey]. PMID- 1503865 TI - [Mechanical ventilation in rats]. AB - In order to create an experimental model of mechanical ventilation that allows functional respiratory studies and different studies related to thorax surgery in small animals, young adult Sprague-Dawley male rats were anesthetised with sodium thiopental and a tracheostomy with a tephlonated catheter was performed. The carotid artery was canulated for arterial blood gas samples, and the cardiovascular system was controlled permanently. A continuous flow time cicled neonatal ventilator, Loosco Amsterdan Infant Ventilator M.K.2, was used for mechanical ventilation. Conventional ventilation with different volumes and pressures were tested. Good adaptation and tolerance and normal blood gases were found with a rate of 60/min; flow rate 0.2 l/min; I:E 1:2; PEED 0 cm H2O; PIP 6.7 +/- 0.5 (mean +/- SD) cm H2O and sharp waves. We conclude that with these very old neonatal ventilators it is possible to ventilate very small experimental animals easily, and allow to small laboratories to do respiratory functional studies or experimental surgery of the thorax. PMID- 1503866 TI - [Intestinal dysmotility-pseudo-obstruction]. AB - Chronic intestinal pseudo-obstruction is defined as a syndrome related to any process which affects intestinal regulation and propulsion. Its origin may be muscular, neurogenic or hormonal, excluding Hirschsprung's disease or any known mechanical obstruction. Between 1989 and 1991, 11 patients with intestinal pseudo obstruction were studied at our centre, and included nine hyperganglionisms B, and two hypoganglionisms) and two visceral myopathies (Berdon's syndrome). Diagnosis was established in all cases by histologic study. The techniques of haematoxylin-eosin, acetylcholinesterase, enolase, protein S-100 and Smith were used in neuropathies and haematoxylin-eosin and Masson's trichromic in myopathies. Intestinal motility was studied by ano-rectal and gastrointestinal manometry in seven and three cases respectively. Gastrointestinal manometry and radiology permitted differentiation of localized and diffuse forms of involvement. Medical treatment consisted of total parenteral nutrition when oral feeding was impossible, and in five cases, cisapride was given, with good results in four. Derivative surgery was performed in cases of diffuse involvement, and resection with anastomosis in those of localized forms. We conclude that: 1. Diagnosis is established according to histologic criteria. 2. Complementary examinations should be directed towards distinguishing localized from diffuse involvement. 3. Cisapride was effective in the treatment of neuropathies in the majority of cases. PMID- 1503868 TI - The seronegative spondyloarthropathies. PMID- 1503867 TI - [Cholelithiasis in childhood. Proposals based on a multicentric study]. AB - Fifty six cases of cholelithiasis in patients aged two months to 15 years (mean age 7.65 years) concerning to 11 hospitals are reviewed. The study protocol followed was the same in all medical records, although own criterions were considered on management performed in each center. From the cases, it follows: 1. Male/female rate is 1/1.5. 2. Symptomatology in infancy is relatively poor and pain localization is not orientative. 3. It was an incidentally finding in 41 per 100 of the cases. 4. Ultrasonography is the best examination procedure rendering diagnosis in the 51 cases it was underwent. 5. Hematologic study was abnormal in six of 46 cases. 6. Medical treatment was not performed in any hospital. 7. Existence of "lithogenic families" seems to be demonstrated. 8. The presence of four patients with Down syndrome in this series must be pointed out. 9. Among total 56 cases, 21 underwent surgical treatment, 29 were conservatively treated, two have died and four patients had spontaneous stone resolution. 10. In the face of these, we propose: A) Surgical treatment in symptomatic cases, porcelain gallbladder and nonfunctionating gallbladder. B) Expectant management and sonographic monitoring in asymptomatic cases. C) Carefully evaluation in patients with predisposing factors and patients with recurrent abdominal pain. PMID- 1503869 TI - New clinical and radiographic features of ankylosing spondylitis. AB - This article reviews new classification criteria for spondyloarthropathies and describes ankylosing spondylitis-like features in nonhuman primates. It describes the literature in general and analyzes specific papers on clinical assessment, outcome measurements, and standardization procedures. The extra-articular manifestations of ankylosing spondylitis and recent papers dealing with the clinical associations and differential diagnosis of ankylosing spondylitis are reviewed. The normal appearance of sacroiliac joints with magnetic resonance imaging and the value of different imaging techniques in the diagnosis of sacroiliitis, are discussed. PMID- 1503870 TI - Psoriatic arthritis. AB - Psoriatic arthritis is an inflammatory arthropathy associated with psoriasis and is classified as a seronegative spondyloarthropathy. It occurs in approximately 5% to 7% of patients with psoriasis. The etiopathogenesis of psoriatic arthritis is not well known, but interaction among genetic, immunologic, and environmental factors is believed to play a key role in the development and clinical expression of the disease. Studies on intercellular interactions, particularly concerning the role of cytokines, growth factors, and intercellular adhesion molecules, have provided new insights into the pathogenesis. A new clinical classification has been introduced based on the experience of a British group. New concepts in the topography (chest, lower limbs, temporomandibular joint) and extra-articular manifestations of the disease have been reported. The usefulness of the erythrocyte sedimentation rate and of bone scintigraphy in the evaluation and follow-up of patients with psoriatic arthritis has also been reported. PMID- 1503871 TI - Immunogenetic basis of the seronegative spondyloarthropathies. AB - This review discusses recent data relevant to better understanding the HLA-B27 association with seronegative spondyloarthropathies. Although much is known about the B27 molecule, its contribution to the pathogenesis of disease is unclear. It is still unknown whether the B27 molecule is involved directly, and whether this is due to the basic function of the molecule, ie, presentation of allele-specific antigenic peptides to the T-cell receptor. Experiments performed with B27 transgenic mice and rats strongly support the view that some unique or special property of the B27 molecule is involved in pathogenesis. However, the data are of a preliminary nature. PMID- 1503872 TI - Infections and the immunopathogenesis of seronegative spondyloarthropathies. AB - Evidence is accumulating for invasion of joints by bacterial antigens in the seronegative spondyloarthropathies. In spite of the inability to isolate bacteria directly from joint material, indirect evidence, provided by antibody and cellular immune studies, points to a local response to local antigen within the joint. Using monoclonal or polyclonal antibodies, several groups have reported detection of bacterial antigens in synovial fluid cells and synovium itself both in reactive arthritis and in undifferentiated forms of seronegative arthritis. There appear to be direct parallels with animal models insofar as bacterial persistence and arthritogenicity are concerned. To date, however, attempts to detect bacterial DNA in joint material, with the possibility of viability that such findings might imply, have been negative. PMID- 1503873 TI - Therapy for the seronegative spondyloarthropathies. AB - Rheumatologists have recently become more circumspect and have begun to demand biologic as well as statistical meaning from the data obtained in therapeutic trials. The same may be applied to therapy for the seronegative spondyloarthropathies. In some respects, the spondyloarthropathies present an even greater problem, because the axial skeleton is even more difficult to evaluate. The studies reviewed here represent the current state of the art, and with the exception of those examining the effects of antimicrobial treatment in reactive arthritis occurring after specific infections, are subject to the same uncertainties. Nonetheless, they represent our immediate point of departure. PMID- 1503874 TI - Bacterial arthritis. AB - The 1991 literature on septic arthritis included a concise review of adult septic arthritis, examples of pseudoseptic arthritis, and two interesting animal studies. One animal study examined the induction of acute synovitis by the intra articular injection of bacterial endotoxin and the cytokines tumor necrosis factor-alpha, and interleukin-1 beta; and the other studied the effects of early and delayed synovectomy in the management of septic arthritis. The predispositions to septic arthritis can be divided into local joint abnormalities, systemic factors, or both. Examples of the local joint abnormalities include osteoarthritis of the hip and apatite-associated arthropathy. Septic arthritis in a patient with rheumatoid arthritis, in a patient with diabetes mellitus and hip arthropathy associated with hemochromatosis, or in a patient with acquired immunodeficiency syndrome and hemophilic arthropathy are examples of how systemic predisposition is coupled with local joint pathology to increase the vulnerability of the host to joint infection. Other examples of systemic disease that predispose to septic arthritis are systemic lupus erythematosus, hypogammaglobulinemia, and human immunodeficiency virus infection, as well as intravenous drug abuse. Unusual microorganisms causing septic arthritis in the adult include Achromobacter xylosoxidans, Moraxella catarrhalis, meningococci, and diphtheroids. Uncommon pathogenesis is represented by a case of intra-articular inoculation of Mycobacterium gastri into the small joint of the hand and a case of mixed bacterial infection of the hip resulting from an extension of a contiguous pelvic infection associated with trauma. Two cases of immune complex glomerulonephritis illustrate the extra-articular complications of septic arthritis: one due to group G streptococcus and the other due to pneumococcus. Finally, septic bursitis is reviewed from the community practice perspective. PMID- 1503875 TI - Arthritis due to tuberculosis, fungal infections, and parasites. AB - A significant proportion of the world's population is afflicted with tuberculosis, fungal infections, or parasitic diseases. The epidemic of acquired immunodeficiency syndrome in developing and developed countries is partially responsible for the increased number of cases. These conditions can cause infectious arthritis and localized bone infection. In addition, reactive arthritis, manifestations that resemble connective tissue disorders, and vasculitis continue to be reported. Prompt diagnosis and adequate treatment of these infections continue to be emphasized in the current literature. PMID- 1503876 TI - Epidemiology, clinical features, and diagnosis of Lyme disease. AB - Lyme disease is the most common vector-borne disease in the United States. Epidemiologic research has contributed to a better understanding of the factors involved in the geographic spread and increased incidence of the disease. Clinical features of Lyme disease, including skin, joint, cardiac, and neurologic involvement, are discussed here, along with recent studies that better characterize these clinical manifestations and more clearly define their immunopathogenesis. The diagnosis of Lyme disease is based on the clinical presentation. Laboratory testing may be helpful but has significant limitations, which we discuss in our review. PMID- 1503877 TI - Viral infections, acquired immunodeficiency syndrome, and rheumatic diseases. AB - There is increasing evidence of a role for viruses in the pathogenesis and etiology of rheumatic diseases. Although definitive evidence of any involvement in diseases such as rheumatic arthritis and systemic lupus erythematosus is currently lacking, there is increasing evidence that viruses may be involved in the pathogenesis of related diseases. In particular, the recent world-wide epidemic of human immunodeficiency virus infection has been associated with the identification of a wide variety of rheumatic manifestations, most notably oligoarthropathies, psoriatic arthropathies, and Reiter's-like syndromes. The spectrum of rheumatic diseases associated with human immunodeficiency virus infection appears to be expanding at a considerable rate. Other viruses have also been shown to be associated with rheumatic disorders, most notably hepatitis viruses, human T lymphotropic virus type I, and parvoviruses. In the latter case, acute arthropathies and those resembling rheumatoid arthritis and Lyme arthritis have recently been identified. This review presents some of the evidence in the recently published literature on the role of different viruses and their implications in the pathogenesis of various rheumatic diseases. PMID- 1503878 TI - Infection as a cause of reactive arthritis, ankylosing spondylitis, and rheumatic fever. AB - Recent advances in understanding the role of infectious agents in the etiology of reactive arthritis (Reiter's syndrome), ankylosing spondylitis, and rheumatic fever are reviewed. The reader is referred to other reviews in this section for discussions of septic, spirochetal, mycobacterial, and fungal arthritis, and human immunodeficiency virus-related connective tissue diseases. PMID- 1503879 TI - Osteoarthritis and crystal deposition diseases. PMID- 1503880 TI - The epidemiology of osteoarthritis of the knee. AB - Estimates of the prevalence and incidence of knee osteoarthritis increase with age and are higher for women. Other differences in such estimates arise due to methodologic variables, including radiographic techniques. The risk for knee osteoarthritis increases with increasing body weight, long-term occupational joint stresses, joint trauma, and probably higher bone mass. Weight restriction and cigarette smoking are associated with reduced risk of knee osteoarthritis. The relationships among these risk factors (eg, bone mass, physical activity, weight, and smoking) and other influences (eg, genetics) remain to be classified. PMID- 1503881 TI - Cartilage research and treatment of osteoarthritis. AB - Research in the past year involving the cartilage structural components, especially the collagens and proteoglycans, has helped to increase our understanding of their complex macromolecular interactions in both normal and osteoarthritic cartilage. The number of factors that regulate the synthesis, deposition in tissue, and catabolism of cartilage, and the complexity of their interactions, continually grows. One of the most significant advances is that the powerful techniques of molecular biology are beginning to be applied to the study of articular cartilage, improving our understanding of chondrogenesis, gene expression in both normal and diseased cartilage, and genetic disorders affecting cartilage. Studies of cartilage in culture suggest the possibility of therapeutic intervention that would have a meaningful impact on disease outcome, the so called chondroprotective therapy, but none has been demonstrated conclusively. Nonsteroidal anti-inflammatory drugs continue to be the most common mode of therapy for osteoarthritis, but recent studies have called this form of treatment into question, suggesting that analgesic therapy may produce equivalent results. PMID- 1503882 TI - Imaging, arthroscopy, and markers in osteoarthritis. AB - Osteoarthritis is the most common form of arthritis occurring in humans, but its diagnosis in early stages continues to be elusive. Early diagnosis is of great potential importance because it would allow identification of individuals at risk for progressive disease and permit early intervention. At present, perhaps even more important, the ability to recognize patients with early, often asymptomatic, disease and the ability to monitor disease progression over time would be most useful for the evaluation of new forms of therapy to prevent, halt, or even reverse osteoarthritis. Thus, 1991 has witnessed the continued search for the ideal indicator of early osteoarthritis. PMID- 1503883 TI - Gout and hyperuricemia. AB - A number of investigators have applied the tools of molecular biology to characterize genes responsible for the control of urate homeostasis and clarify the roles of uric acid precursors in inflammation. Some, using the tools of clinical medicine, continue to provide novel descriptions of gout and to explore better ways for evaluating hyperuricemia and for understanding the pathophysiology of disorders such as familial urate nephropathy. Others link the disciplines of basic research and clinical medicine in approaching the perplexing questions of crystal-induced inflammation. PMID- 1503885 TI - The seronegative spondyloarthropathies. PMID- 1503884 TI - Calcium pyrophosphate crystal deposition disease and other crystal deposition diseases. AB - A number of cells, chemotactic factors, and inflammatory mediators are implicated in the complex mechanisms underlying crystal-mediated inflammation. Interleukin 8, released from mononuclear cells that have been exposed to urate and other crystals, is a potent chemotaxin and activator of neutrophils. Experimental and clinical observations suggest that joint movements, local biomechanical factors, and previous joint damage may play a role in influencing the intensity of microcrystalline synovitis and the distribution of articular and periarticular crystal deposits in both calcium pyrophosphate dihydrate crystal deposition disease and gout. There are rare reports of extra-articular calcium pyrophosphate dihydrate crystal deposition in tendons, bursae, dura mater, and ligamentum flavum (with radiculomyelopathy) and of massive "tumoral," tophuslike, periarticular calcium pyrophosphate dihydrate crystal deposits. Synovial fluid levels of ATP, the main substrate for nucleoside triphosphate pyrophosphohydrolase ectoenzyme, which cleaves ATP-releasing inorganic pyrophosphate, are higher in patients with calcium pyrophosphate dihydrate crystal deposition disease than in those with other arthritides, and the levels correlate with inorganic pyrophosphate concentrations. Further reports of acute calcific periarthritis of the first metatarsophalangeal joint (hydroxyapatite pseudopodagra) in young women have been described. The mitogenic response of fibroblasts to stimulation with basic calcium phosphate crystals is accompanied by induction and secretion of collagenase and neutral proteases, implicating a role for the crystals in the pathogenesis of both synovial proliferation and joint damage in chronic basic calcium phosphate crystal-associated arthropathy. Subcutaneous cholesterol crystal deposition with tophus formation is extremely rare and has been described in a patient with scleroderma and calcinosis cutis. PMID- 1503886 TI - Infectious arthritis and immune dysfunction. PMID- 1503887 TI - Osteoarthritis and crystal deposition disease. PMID- 1503888 TI - Functional abnormalities in the intestine associated with mucosal mast cell activation. AB - Mast cells are a significant component of the mucosa in the gastrointestinal tract. There is increasing evidence that these cells are involved in the pathophysiology of various intestinal disorders ranging from food allergy to inflammatory bowel disease. When activated, mast cells release a host of potent mediators and cytokines which are capable of inducing pathophysiology. The bulk of the evidence has come from hypersensitivity studies in experimental animals sensitized either by parasitic infection or by active immunization to an antigen using adjuvants which stimulate IgE production. Subsequent antigen challenge of the gut results in mast cell activation associated with alterations in intestinal functions including ion transport and epithelial permeability. Intestinal secretory transport responses are inhibited by antagonists of mast cell mediators and neurotoxins, implicating mast cell-nerve interactions with the epithelium. In genetically mast cell-deficient mice, antigen-induced secretion is reduced approximately 70% and this component is not affected by neural or mast cell inhibitors; adoptive transfer of bone marrow containing mast cell precursors derived from congenic normal mice restores the complete antigen response. These results provide more direct proof that mast cell activation causes abnormal gut function. Recently, we have begun studies which indicate that activation of mast cells induces ion secretion in surgically resected human intestine. Reduced secretory responses in specimens from patients with IBD suggest that mast cells may play a role in the pathophysiology of inflammatory bowel disease. PMID- 1503889 TI - The mucosal immune system: features of inductive and effector sites to consider in mucosal immunization and vaccine development. PMID- 1503890 TI - Cholera toxin conjugates for intragastric vaccination against herpes simplex virus type 2. AB - In this study, we tested the hypothesis that enteric immunization with cholera toxin (CTX) conjugated to glycoprotein D (gD) of herpes simplex virus type 2 (HSV 2) or a peptide corresponding to residues (1-23) of gD (gD(1-23)) would induce relevant antiviral immunity. Intraperitoneal (IP) immunization of mice with CTX gD(1-23) conjugate induced anti-HSV-2 sera antibody responses which correlated with protection from a lethal IP challenge with HSV-2. Intragastric (IG) immunization of mice with the same conjugate or a CTX-gD conjugate did not result in measurable anti-HSV-2 responses in sera or vaginal washings and only small numbers of anti-HSV-2 antibody-secreting cells (ASC) were found in intestinal lamina propria cell and splenocyte preparations. In comparison, anti-CTX responses were detected in sera and vaginal washings after IG immunization with CTX and anti-CTX ASC in lamina propria cell preparations accounted for 5-10% of total ASC detected at this site. No significant differences in the survival of mice immunized with the conjugates were noted after a lethal intravaginal (IVAG) challenge with HSV-2. The poor enteric immunogenicity of gD(1-23) and gD conjugated to CTX was attributable to proteolysis in the gastrointestinal tract. These results indicate that although peptide-CTX conjugates can induce protective immune responses when administered parenterally, it may not be feasible to use peptides as the basis of an oral vaccine unless methods are developed to protect these antigens from degradation in the gastrointestinal tract. PMID- 1503892 TI - A strategy for the control and prevention of cholera in Africa. Declaration. PMID- 1503891 TI - The use of the hu-PBL-SCID mouse model to study lymphocyte homing and responsiveness to recall antigens. AB - SCID mice were injected intraperitoneally with human peripheral blood lymphocytes (PBL) that had been previously stimulated with pokeweed mitogen (PWM) for two days to generate activated B cells. After two weeks, serum and gut washes obtained from SCID mice reconstituted with human PBL (hu-PBL-SCID mice) contained human IgA, IgG, and IgM indicating the successful survival of human lymphoid cell grafts in both mucosal and nonmucosal tissues of the SCID mice. Human IgA plasma cells could be detected by immunofluorescence microscopy in the lamina propria of the small intestine, while IgM plasma cells predominated in the spleen. The results suggested that PWM-activated plasma cell precursors homed to the spleen and the lamina propria of the SCID mouse where they differentiated into plasma cells. In vivo stimulation of hu-PBL-SCID mice with diphtheria and tetanus toxoids (DT/TT) elicited a primary (IgM) immune response pattern rather than a secondary (IgG) response. Antigen-specific antibody-secreting cells were found in the spleen and lamina propria after immunization. The microenvironment of the hu PBL-SCID mice may select virgin B cells subsets over memory B cell clones. PMID- 1503893 TI - Infected areas as of 9 January 1992. PMID- 1503894 TI - Implications of an overview of chemotherapy in advanced ovarian carcinoma. PMID- 1503896 TI - The Walter Herbert Lecture. Control of cell motility and tumour invasion by extracellular matrix interactions. AB - Integrins are heterodimeric transmembrane proteins with large ectodomains and a short cytoplasmic tail inside the cell. They mediate cell adhesion to extracellular matrix proteins and to the surfaces of other cells. In many cases the sequence recognised by the integrins in the extracellular matrix proteins is the tripeptide Arg-Gly-Asp (RGD). Short synthetic peptides containing this sequence can inhibit invasion in vitro and tumour dissemination in vivo. Thus, the alpha 5 beta 1 fibronectin binding integrin appears to be the key integrin in the invasion of at least melanoma, osteosarcoma and glioblastoma cells. Modulation of the level and activities of this integrin can suppress invasion, whereas the alpha v beta 3 vitronectin binding integrin appears to be associated with increased invasiveness. There is increasing evidence that some of these effects are mediated through signals elicited by the binding of integrins to their target proteins. This possibility has generated a great deal of interest in the cytoplasmic molecules that might mediate the integrin-associated signalling. PMID- 1503895 TI - Modulation of cis-diamminedichloroplatinum(II) resistance: a review. AB - In this review an inventory is made of agents used to circumvent cis diamminedichloroplatinum(II) (CDDP) resistance in vitro and in vivo. Agents that affect CDDP accumulation and membrane related systems, cytoplasmic defense mechanisms, as well as DNA accessibility and repair are reviewed. In resistant cell lines that have decreased accumulation, this can be restored by hyperthermic treatment. With or without effects on accumulation compounds that affect cell signal transduction often increase CDDP cytotoxicity. Calcium channel blockers and calmodulin inhibitors do not seem to be uniformly good modulators of CDDP resistance. For transduction modulators as well as cellular calcium affecting agents mechanisms are mainly unclear or controversial. Glutathione appears, with the now available agents, to be the most promising target for modulation of cytoplasmic defense mechanisms. At the nuclear level the inhibition of DNA repair related enzymes as well as the use of modified nucleosides to interfere with repair is studied in various cell lines. Results with these agents suggest opportunities for clinically feasible cytotoxicity modulation. DNA accessibility could in vitro be affected, but seems to be an unreliable target for modulation. Whenever possible the resistance mechanism affected and the mode of action of the modulator are discussed. As an alternative for modulation another method of overcoming CDDP resistance namely the application of CDDP analogues is considered. PMID- 1503897 TI - Growth control by epidermal growth factor and transforming growth factor-alpha in human lung squamous carcinoma cells. AB - Although EGF receptor expression is generally elevated in human lung squamous carcinoma, the biological significance of this phenomenon and the role of EGF and TGF-alpha in this disease are poorly understood. We have investigated three human lung squamous carcinoma cell lines (NX002, CX140 and CX143) and have shown, using an antibody (EGFR1) directed against the EGF receptor, that the majority of cells in all three lines express the EGF receptor. Using a ligand binding assay, Scatchard analysis indicated high concentrations (1,300-2,700 fmol mg-1 protein) of a single low affinity binding site (Kd = 3-5 nM) within these lines. Addition of EGF or TGF-alpha at concentrations greater than 0.1 nM resulted in growth inhibition of all three lines and this was associated with an accumulation of cells in the G2/M phase of the cell cycle. Growth inhibitory effects were not explained by an enhancement of cellular differentiation as monitored by involucrin expression and the ability to form cornified envelopes. While the presence of EGF could not be detected in medium conditioned by the NX002 cell line, mRNA for TGF-alpha was detected in all three lines suggesting the possibility of an autocrine loop. These results together with reports of growth inhibition by EGF and TGF-alpha in other systems suggest that EGF and similar molecules might have a growth regulatory role in lung cancer cells and modulation of such may have therapeutic potential. PMID- 1503898 TI - The binding of cis-dichlorodiammineplatinum(II) to extracellular and intracellular compounds in relation to drug uptake and cytotoxicity in vitro. AB - The biological consequence of the binding of cis-dichlorodiammineplatinum(II) (cis-DDP) to serum protein as well as to cellular components in general, was studied on human NHIK 3025 cells in vitro. As expected, we found that the cytotoxicity of cis-DDP was lost by binding to serum protein, and that protein bound platinum was impermeable to the cells. As we have previously shown that electropermeabilisation may transiently increase the influx of cis-DDP, we applied this technique in an attempt to increase the efflux of cis-DDP or any other cytotoxic intermediates. Our data demonstrate that if cells are electropermeabilised shortly after treatment with cis-DDP, cell survival increased. This indicates that cis-DDP in an active form is released from the cells; furthermore, the plasma membrane represents a barrier against efflux, as it has also been shown to be against influx of active cis-DDP. Thus, our data are consistent with the idea that there must be an intracellular pool of either cis DDP, or some biologically active intermediates, in cells treated with this drug. Additionally, our data indicate that the binding rate of cis-DDP to biological molecules is much quicker intracellularly than in the extracellular environment: We found the biological half-life at 37 degrees C to be about 2.1 h in human serum and about 11 min inside our cells. PMID- 1503899 TI - The effects of ICRF-154 in combination with other anticancer agents in vitro. AB - We studied the effects of ICRF-154 in combination with 11 anticancer agents on four human leukaemia cell lines. Cells were incubated for 3 days in the presence of two drugs (ICRF-154 and one other), and cell growth inhibition was determined by MTT assay. Effects of drug combinations at the ID50 level were analysed using the isobologram method (Steel). In the lymphoblastic leukaemia cell lines, MOLT 3, HSB, and B-ALL, supra-additive effects were observed for ICRF-154 in combination with amsacrine, bleomycin, doxorubicin, and etoposide. Additive effects were observed for its combinations with cisplatin, CPT-11, cytosine arabinoside, 5-fluorouracil, mitomycin C, and vincristine. Sub-additive to protective effects were observed in combination with methotrexate. In an erythroleukaemia cell line, K-562, no drug showed supra-additive effects with ICRF-154, while sub-additive to protective effects were observed for ICRF-154 in combination with cisplatin and methotrexate. The other drugs showed additive effects with ICRF-154. These results indicate that the combined effects of ICRF 154 with other agents vary, depending on the cell line. Against lymphoid malignancies, ICRF-154 would be advantageous when administered simultaneously with many anticancer agents. Of such agents, amsacrine, bleomycin, doxorubicin, and etoposide are the most suitable, while methotrexate is least suitable for such combined treatment. PMID- 1503900 TI - Is there a relationship between regional microsphere distribution and hepatic arterial blood flow? AB - The relationship between hepatic arterial albumin microsphere distribution and hepatic arterial blood flow and the effects of regional angiotensin II were studied in a rat liver metastases model. Hooded-Lister rats were inoculated subcapsularly with 2 x 10(6) HSN sarcoma cells. At 20 days, hepatic arterial blood flow was measured using the reference microsphere technique. Animals then randomly received 50 microliters hepatic arterial saline or albumin microspheres (40 microns, 20 mg ml-1). Hepatic arterial blood flow measurements were then repeated at 5 min. After 5 min, animals were killed and tissues were weighed and counted in a gamma well counter. There were no significant differences between the hepatic blood flow measurements recorded before and after the control hepatic arterial saline infusion. However, regional albumin microspheres produced a significant reduction in tumour and normal liver blood flow and an 80% reduction in mean T/N blood flow ratio. Regional albumin microspheres were delivered to tumour in greater proportions (mean T/N ratio 3.89, SE 0.49) than would be expected from baseline hepatic arterial blood flow (mean T/N ratio 1.28, SE 0.22. P = 0.006). There was no correlation between T/N for baseline blood flow and albumin microsphere distribution. PMID- 1503901 TI - Uptake of plasma lipids by tissue-isolated hepatomas 7288CTC and 7777 in vivo. AB - The uptake of myristic (C14:0), palmitic (C16:0), palmitoleic (C:16,N-7), stearic (C18:0), oleic (C18:1,N-9), linoleic (C18:2,N-6) and arachidonic (C20:4,N-6) acids from plasma free fatty acids (FFA), triglycerides (TGA), phospholipids (PL) and cholesterol esters (CE) was measured in tissue-isolated hepatomas 7288CTC and 7777 in vivo. Adult tumour-bearing Buffalo rats were fed a normal chow diet ad libitum and were subjected to darkness from 1800 to 0600 h. Arterial plasma levels of FFA, TGA, PL and CE were increased during the dark period without change in fatty acid compositions. Arteriovenous difference measurements of tumour lipid uptake were performed between 0600 and 0900 h and included both high (dark) and low (light) arterial blood lipid concentrations. The rate of lipid uptake from each lipid class was directly dependent on the rate of supply of the lipid to the tumour. The efficiency of uptake, however, depended on the type of plasma lipid and the tumour. During one pass of arterial blood, hepatoma 7288CTC (n = 5 to 13) removed 46, 33, 36 and 31%, and hepatoma 7777 (n = 7 to 9) removed 48, 50, 52 and 49% of the fatty acids supplied in FFA, TGA, PL and CE, respectively. Perfusion of tissue-isolated tumours in situ with donor blood containing plasma free (1-14C)palmitic acid showed that 14C-palmitic acid was removed from the arterial blood and was incorporated into tumour lipids and that 14CO2 was released into the tumour venous blood. Uptake of the seven fatty acids over a 24 h period was greatest from PL greater than TGA greater than FFA greater than CE and was estimated to total 18.1 +/- 3.5 mg fatty acids g-1 for hepatoma 7288CTC and 25.9 +/- 3.5 mg fatty acids g-1 for hepatoma 7777. Both hepatoma 7288CTC and 7777 grew at a rate of about 1 g day-1 and contained 13.4 +/- 2.5 and 10.6 +/- 3.9 mg of these 7 fatty acids g-1 tumour wet weight, respectively. We conclude that these two tumours obtain all of the fatty acids needed for daily growth from host arterial blood. PMID- 1503902 TI - The effect of omega-6 and omega-3 fatty acids on 3H-thymidine incorporation in hepatoma 7288CTC perfused in situ. AB - Ingestion of diets containing corn oil or marine fish oils is known to increase or decrease, respectively, the growth of transplantable rodent tumours. The active agents in these oils have been identified as linoleic acid (in corn oil) and omega-3 fatty acids (in marine oils), but it is still not known how they influence the tumour growth processes. In these experiments we examined the effects of plasma free omega-6 and omega-3 fatty acids on the rate of 3H thymidine incorporation in tissue-isolated hepatoma 7288CTC perfused in situ. Host Buffalo rats were fed an essential fatty acid-deficient diet. Plasma and tumours in these animals contained low endogenous levels of both omega-6 and omega-3 fatty acids. Perfusion of these tumours for 2 h with donor whole blood containing added omega-6 free fatty acids, including 0.5 mM linoleic (C18:2,N-6), gamma-linolenic (C18:3,N-6), dihomo-gamma-linolenic (C20:3,N-6) or arachidonic acids (C20:4,N-6), increased the rate of 3H-thymidine incorporation. Linoleic acid was about three times more effective than the other omega-6 fatty acids. Typical hyperbolic substrate-saturation curves were observed as the plasma free linoleate or arachidonate concentration was increased. When perfused alone plasma free omega-3 fatty acids had no effect on tumour 3H-thymidine incorporation, but in the presence of linoleic acid the omega-3 fatty acids, alpha-linolenic (C18:3,N-3) and eicosapentaenoic (C20:5,N-3), competitively inhibited both tumour linoleate uptake and the stimulative effect on 3H-thymidine incorporation. The results suggest that the ambient plasma free linoleic and arachidonic acid concentrations in host arterial blood directly influence the rate of tumour DNA synthesis. Plasma free omega-3 fatty acids appear to modulate the effect of linoleic acid by competitively inhibiting its uptake. These relationships could explain the actions of dietary linoleic and omega-3 fatty acids on tumour growth in vivo. PMID- 1503904 TI - Effects of agents which inhibit the regulation of intracellular pH on murine solid tumours. AB - Cell killing can be achieved in an acidic environment in tissue culture (medium pH less than 7.0) by agents (nigericin, carbonylcyanide-3-chlorophenylhydrazone (CCCP)) which transport protons from the extracellular space into the cytoplasm. Cell killing is enhanced when these agents are used in combination with compounds (amiloride, 4,4'-diisothiocyanostilbene-2,2'-disulfonic acid (DIDS)) which inhibit the membrane-based exchangers responsible for the regulation of intracellular pH (pHi). We describe experiments which assess the ability of these agents to kill tumour cells in spheroids and in vivo. Both nigericin and CCCP were observed to penetrate tissue based on their ability to kill tumour cells in spheroids. The mean extracellular pH (pHe) of the KHT fibrosarcoma and the EMT-6 sarcoma were observed to be 0.21 and 0.32 pH units more acidic than the mean pHe in muscle tissue. Intraperitoneal (i.p.) administration of the vasodilator hydralazine (10 mg kg-1) caused a reduction of the mean pHe of the KHT but not the EMT-6 tumour. Nigericin (2.5 mg kg-1, i.p.) plus amiloride (10 mg kg-1, i.p.) followed 30 min later by hydralazine (10 mg kg-1, i.p.) reduced the surviving fraction of cells in the KHT and EMT-6 tumours, but had minimal effects on growth delay. When KHT tumours were treated with 15 Gy X-rays followed immediately by nigericin plus amiloride and hydralazine a reduced surviving fraction as well as an increase in tumour growth delay was observed compared to radiation alone. The administration of nigericin (2.5 mg kg-1, i.p.) or the combination of nigericin (2.5 mg kg-1, i.p.) followed by hydralazine (10 mg kg-1, intravenous (i.v.)) resulted in reductions of tumour pHi of 0.27 and 0.29 pH units respectively as determined by 31P magnetic resonance spectroscopy (MRS). Our results show that the combination of nigericin and hydralazine (with or without amiloride) can kill cells in rodent solid tumours and that cell killing is associated with a reduction in the mean pHi of tumour cells. PMID- 1503903 TI - Synergism between a novel amphibian oocyte ribonuclease and lovastatin in inducing cytostatic and cytotoxic effects in human lung and pancreatic carcinoma cell lines. AB - A novel anti-tumour amphibian oocyte RNase, ONCONASER (ONC), previously known as P-30 Protein, is in the clinical trials. The effect of ONC alone and in combination with lovastatin (LVT), an inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase, a rate-limiting enzyme of mevalonate (MVA) and cholesterol synthesis pathway, in three human tumour cell lines ASPC-1 pancreatic, A-549 lung, and HT-520 lung carcinomas, has been presently studied. A synergism between ONC and LVT in inducing the cytostatic and cytotoxic effects was observed. The cytostatic effect, seen during the early phase of the treatment with this combination of drugs was manifested as prolongation of the cell cycle duration, especially of the G1 phase; cell death was apparent after 72 h of treatment. The synergistic effect of ONC and LVT was also evident in the clonogenicity assays. Both LVT lactone and its in vitro activated beta-hydroxy acid form, alone and in respective combinations with ONC, exerted similar degree of growth suppression. The effects of both forms of LVT (used alone or in combination with ONC) were reversed by MVA, which suggests that HMG-CoA reductase inhibition is a primary mechanism of LVT action. The data indicate that the LVT lactone can be activated intracellularly by tumour cells studied, and that the combination of ONC with LVT can produce significantly enhanced anti-tumour activities. PMID- 1503905 TI - Changes in expression of alpha 6/beta 4 integrin heterodimer in primary and metastatic breast cancer. AB - The alpha 6/beta 4 integrin complex has been shown to be expressed in murine tissues at the basolateral aspect of most epithelial cells including the mammary epithelium, thus suggesting that this heterodimer may interact with components of the basement membrane. Because transformation of mammary epithelium frequently results in disappearance of basement membranes and loss of cell polarisation we have analysed in the present study whether expression of the alpha 6/beta 4 complex is altered in human breast tumours. The results of the present study confirm that in human mammary gland alpha 6 and beta 4 subunits colocalise at the basolateral aspect of the epithelium. While in benign breast lesions this distribution pattern remains mostly unchanged, in primary carcinomas the expression of both chains is either redistributed over the cells surface or significantly reduced. This altered pattern of expression is paralleled by the lack of detection of basement membrane laminin and collagen type IV. In metastatic lesions the expression of the heterodimer is maintained in most of the lymphnodal foci, but less frequently detected in metastasis localised in the pleural cavity and in parenchymal tissues. These findings indicate that in breast epithelium expression of the alpha 6/beta 4 heterodimer is modulated by the presence of basement membrane and is possibly influenced by microenvironmental factors as suggested by the different pattern of alpha 6/beta 4 expression in nodal and extranodal metastatic foci. PMID- 1503906 TI - The influence of hydralazine on the vasculature, blood perfusion and chemosensitivity of MAC tumours. AB - We have studied the influence of the peripheral vasodilator hydralazine (HDZ) on the vasculature and blood perfusion of two members of a series of subcutaneous murine adenocarcinomata of the colon (MAC tumours), and the influence of HDZ on the efficacy and/or toxicity of TCNU and melphalan. The fluorescent DNA stain Hoechst 33342, showed that HDZ caused a shutdown of tumour vasculature, related in magnitude to both dose and tumour differentiation state; 10 mg kg-1 caused an 80% vascular shutdown of well differentiated MAC 26 tumours, but only a 50% shutdown of the poorly differentiated MAC 15A tumours. 2.5 mg kg-1 was ineffective. The blood perfusion marker 99mTc-HMPAO showed that the normal perfusion of MAC tumours was consistently markedly less than that of lung, liver or kidneys (4-5% of lung perfusion). HDZ (10 mg kg-1) decreased MAC 26 perfusion by 63%, and that of MAC 15A by 20%. Again, 2.5 mg kg-1) was ineffective. Use of in vivo to in vitro clonogenic assays showed that HDZ (10 mg kg-1) potentiated the efficacy of melphalan (1-10 mg kg-1 i.p.) by a factor of 2.1, and increased the efficacy of TCNU (1-10 mg kg-1 i.v., factor = 1.7) when given 10 or 15 min respectively after dosing. However, the addition of HDZ increased the acute bone marrow toxicity of melphalan, but not that of TCNU. The clinical relevance of these results is discussed. PMID- 1503907 TI - Serum concentration of the cross-linked carboxyterminal telopeptide of type I collagen (ICTP) is a useful prognostic indicator in multiple myeloma. AB - Type I collagen is the main collagen type found in mineralised bone. Specific immunoassays for PICP (carboxyterminal propeptide of type I procollagen) and ICTP (cross-linked carboxyterminal telopeptide region of type I collagen) allow simultaneous assessment of the synthesis and degradation of type I collagen in serum samples, respectively. Our aim was to find out whether these metabolites of type I collagen are useful markers for following bone turnover and evaluating treatment response in multiple myeloma, which is a good model disease of excessive osteolysis. Fifteen consecutive patients were studied before and throughout their treatment. Samples for serum PICP and ICTP were collected before starting each treatment course of melphalan and prednisolon. Response to treatment was evaluated by following the changes in M protein and bone roentgenograms. The disease was progressing in four and regressive in 11 patients, but in four of these a recurrence occurred. In nonresponders the ICTP concentration was permanently elevated despite treatment. In responders both increased or normal levels of ICTP were initially observed, but they returned to or remained in the reference interval during treatment. The ICTP concentration increased upon recurring disease. There was a strong correlation between the extent of bone lesions and ICTP. There was no correlation between ICTP and PICP, the latter mainly remaining within the reference range, a finding that suggests no change in bone formation. ICTP was a significant predictor for survival in this patient group (P less than 0.05). We conclude that ICTP is a specific and sensitive marker for bone resorption. Simultaneous use of serum ICTP and PICP offers an additional and easy means to follow bone turnover and evaluate the response to therapy in multiple myeloma. PMID- 1503908 TI - Antigenic modulation of metastatic breast and ovary carcinoma cells by intracavitary injection of IFN-alpha. AB - Antigenic modulation of major histocompatibility and tumour associated antigens was observed in neoplastic cells obtained from patients with pleural and abdominal effusions of breast and ovary carcinomas following a single intracavitary dose of 18 x 10(6) U recombinant IFN-alpha. This regimen resulted in antigenic modulation in seven out of 11 tested cases, suggesting a potential, although limited, responsiveness of at least a fraction of breast and ovary carcinoma cells to in situ biomodification with IFN-alpha. PMID- 1503909 TI - Modification of the volumetric growth responses and steady-state hypoxic fractions of xenografted DLD-2 human colon carcinomas by administration of basic fibroblast growth factor or suramin. AB - We studied the growth characteristics and hypoxic fractions of DLD-2 human colon tumours xenografted into male nude mice either in the unperturbed state or after i.p. injection (q.i.d. x 7) of basic fibroblast growth factor (0.25 mg kg-1) or suramin (50 mg kg-1). Hypoxic fractions were measured by clonogenic excision assay 1 day after administration b FGF or suramin was stopped. As compared to controls, the growth of tumours in b FGF treated mice was increased by a factor of 1.5 as indicated by the relative volumes of tumours on the day of excision. Similarly, suramin decreased the growth of DLD-2 tumours by a factor of 1.6. The percentage of hypoxic cells in control neoplasms was 42.9% (95% confidence limits 34.2-52.1%). In mice that received basic fibroblast growth factor injections, hypoxic fractions decreased to 19.1% (95% confidence limits 13.5-26.9%). In contrast, in mice treated with suramin, the percentage of hypoxic cells increased to 74.0% (95% confidence limits 65.3-83.9%). These data indicate that the biology of solid tumours can be significantly modified by alteration of growth factor status. PMID- 1503910 TI - Separable growth and migration factors for large-cell lymphoma cells secreted by microvascular endothelial cells derived from target organs for metastasis. AB - Metastatic variant sublines of the murine large-cell lymphoma cell line RAW117 were tested for their growth and migration properties in vitro in medium conditioned by soluble factors released from syngeneic mouse liver-, lung-, and brain-derived microvessel endothelial cells. Medium conditioned with hepatic sinusoidal endothelial cells stimulated the growth of highly liver-colonising (RAW117-H10) and highly liver- and lung-colonising (RAW117-L17) sublines at higher rates than the poorly metastatic parental line (RAW117-P) (H10 greater than L17 greater than P). Medium conditioned with lung microvessel endothelial cells selectively stimulated the growth of the lung-colonising RAW117-L17 subline. Medium conditioned with brain microvessel endothelial cells showed no growth selectivity, and equivalently stimulated the growth of various RAW117 cell sublines. Medium conditioned with hepatic sinusoidal endothelial cells preferentially promoted the migration of the liver-colonising H10 and L17 sublines, and medium conditioned with lung endothelial cells differentially stimulated the migration of the lung-colonising L17 subline; whereas medium conditioned with brain endothelial cells only slightly stimulated the migration of L17, but not H10 or P cells. Fractionation of medium conditioned with hepatic sinusoidal endothelial cells by DEAE Sephacel anion exchange chromatography revealed that the growth-stimulating activities were clearly separable from migration-stimulating activities. The growth- and migration-stimulating activities released from organ microvessel endothelial cells may be important in determining the ability of RAW117 cells to selectively form metastatic colonies in particular organs. PMID- 1503911 TI - Immunohistological examination of the inter- and intracellular distribution of O6 alkylguanine DNA-alkyltransferase in human liver and melanoma. AB - The tissue and cellular distribution of the DNA repair protein O6-alkylguanine DNA-alkyltransferase (ATase) is an important question in relation to the response of tumour and normal tissues to chemotherapeutic regimes employing alkylating agents such as methyltriazenes and nitrosoureas. In order to examine this issue by immunostaining, we have raised a rabbit antiserum to apparently pure recombinant human enzyme. The antiserum is highly specific and sensitive, detecting a band at 24 kDa on western blots of crude extracts of ATase-expressing human lymphoblastoid cells, liver and melanoma. Adjacent sections of acetone or formalin fixed normal human liver and subcutaneous malignant melanoma were reacted with preimmune serum or antiserum and an immunoperoxidase detection system with silver enhancement was used to locate binding of the primary antibody to the antigen. In sections reacted with preimmune serum or with antigen preadsorbed antiserum, only faint cytoplasmic and little or no nuclear staining was seen. In contrast, using antiserum, the reaction in positively staining cells was very intense and predominantly nuclear. In the liver, there was interindividual variation in the cellular distribution of reaction with staining present in all discernable cell types in most samples but confined to the hepatocytes and bile duct epithelial cells in others. In the melanoma sections, all discernable cell types showed mainly nuclear staining: the intensity of staining varied between tissue samples and there was evidence of a range of intermediate staining intensities with some melanoma cells showing no detectable reaction. PMID- 1503912 TI - Prognostic implications of p53 protein, epidermal growth factor receptor, and Ki 67 labelling in brain tumours. AB - The expression of p53 protein, epidermal growth factor receptor (EGFR), and Ki-67 nuclear antigen was examined by immunohistochemistry in biopsies of 16 types of human brain tumours, including 43 astrocytomas. P53 protein, almost certainly its mutant form, was expressed in seven of the 16, and EGFR in 11 of the 16 types of tumours. In astrocytomas both the proportion of tumours which expressed p53 or EGFR increased with grade of malignancy as did the mean Ki-67 labelling index (LI): p53-0% in grade 1, 17% in grade 2, 38% in grade 3, 65% in grade 4; EGFR-0% in grade 1, 33% in grade 2, 85% in grade 3, 95% in grade 4; mean Ki-67 L1-1.1% in grades 1 and 2, 8.3% in grade 3, and 13.4% in grade 4. Astrocytomas which expressed p53 or EGFR had a significantly higher Ki-67 LI at P less than 0.05 (11.8% and 10.7%, resp.) than those that did not (6.2% or 4.1%, resp.). Patients with astrocytomas expressing p53 or EGFR had a significantly reduced survival (P = 0.035 and P = 0.007, resp.): only 11% of the p53 + ve and 13% of the EGFR + ve patients were alive at 100 weeks following diagnosis compared to 36% of p53-ve or 60% of EGFR-ve patients. Patients with Ki-67 LI greater than 5% had a reduced survival (P less than 0.0001)--none survived beyond 86 weeks following diagnosis, whilst 63% of patients with less than 5% positive cells were still alive at 100 weeks. The univariate analysis showed that in astrocytomas expression of p53 mutants, EGFR protein, and Ki-67 greater than 5% are associated with malignant progression and poor prognosis. The multivariate analysis revealed that only tumour grade and Ki-67LI were independent prognostic factors for survival. PMID- 1503913 TI - Reduced risk of colorectal cancer among recent generations in New Zealand. AB - Male and female age standardised mortality and incidence rates of colorectal cancer have increased over the most recent 30 years in New Zealand. Among men and women aged 40 to 74, age standardised mortality and incidence rates increased 18 to 105%. However, age standardised mortality and incidence rates among younger men and women have declined from 14 to 69%. Analysis of trends in age specific mortality and incidence rates indicates that the occurrence of colorectal cancer has been declining equally for men and women in successive cohorts born about 1943 to 1953 in New Zealand. This decline in the frequency of colorectal cancer among recent generations was apparent for both the right and left sides of the colon and the rectum. Age-specific trends in coronary heart disease and breast cancer differed from those apparent for colorectal cancer, suggesting that the factors producing the reduction in colorectal cancer risk may affect these diseases among different age groups or may not be of major aetiological importance in these diseases. These trends provide empirical evidence that the occurrence of colorectal cancer can be reduced by at least 50% with a substantial component of the risk being determined before the age of 30. Further study is needed to establish whether changes in risk factors at older ages contribute to the prevention of the disease. PMID- 1503914 TI - Time trends in accuracy of classification of testicular tumours, with clinical and epidemiological implications. AB - Initial classifications of 1009 testicular tumours were reviewed as part of a population based survey of all testicular neoplasms in Victoria, Australia, between 1950 and 1978. All reviews were made by one of two pathologists at the Peter MacCallum Cancer Institute, using the system of the British Testicular Tumour Panel. Accuracy of diagnosis varied markedly over the time period and with pathological category. Seven cases were initially designated malignancies but were determined to be non-malignant conditions upon review. In each decade, review reduced the proportion of seminomas and increased the proportion of non seminoma germ cell tumours (NSGCT) and non germ cell tumours. Reclassification resulted in changed age specific incidences of seminoma and NSGCT, most noticeably in 1950-59. Trends in age standardised incidence of seminoma and NSGCT were not affected by reclassification although the values were. The trend in age standardised incidence of non germ cell tumours was affected by reclassification. The implications of the changes in classification for epidemiological studies and clinical management are discussed. PMID- 1503915 TI - A randomised trial of second-line hormone vs single agent chemotherapy in tamoxifen resistant advanced breast cancer. AB - Sixty patients with advanced breast cancer unresponsive to tamoxifen have been randomised to receive four course of mitozantrone, 14 mg m-2 (n = 30) intravenously every 3 weeks (9 weeks total) or megesterol acetate, 160 mg bd (n = 30). One in three patients (11 from each group) had substantial disease control for a minimum period of 6 months i.e., lack of progression; seven patients (23%) showed objective response to mitozantrone compared to four (13%) receiving megesterol. Non-progressive disease occurred in all sites, including visceral metastases and receptor negative patients. There were no significant differences between treatment groups in the median time (5 months each) to disease progression response duration or survival (13 months megesterol, 11 months mitozantrone) from commencing second-line therapy. Toxicity was considerably higher in the mitozantrone group. Second-line hormonal therapies can produce similar therapeutic results as those achieved from a short course of a 'short option' single agent cytotoxic in patients who were previously thought hormone insensitive. Provided that the patient does not have life threatening disease a trial of megesterol acetate is worth consideration in that it does not prejudice subsequent response to combination cytotoxic chemotherapy. PMID- 1503916 TI - Phase I study of intra-arterial interleukin-2 in squamous cell carcinoma of the head and neck. PMID- 1503917 TI - Completeness of cancer and death follow-up obtained through the National Health Service Central Register for England and Wales. AB - For the last 20 years the National Health Service Central Register (NHSCR) has been used as the principal source of follow-up for mortality, and often for cancer incidence, in many cohort and clinical follow-up studies in England and Wales. Completeness of notification of childhood cancer registrations and deaths from the NHSCR was investigated by comparison between cancers and deaths notified to the Childhood Cancer Research Group (CCRG) from this source and notifications received directly from regional cancer registries and the national death registry. Six thousand, seven hundred and seventy-six (91.8%) of 7,379 cancers incident 1971-84, and 588 (95.8%) of 614 deaths occurring 1953-88, were successfully notified. Failures in cancer notification occurred mainly between the regional cancer registries and the National Cancer Register (3.3%), and between the National Cancer Register and the NHSCR (3.0%). An additional 1.9% of cancer notifications failed between the NHSCR and the CCRG. Incompleteness of registration of childhood cancers by regional cancer registries was estimated to be 4.7%. A total of 12.5% of incident childhood cancers were not notified by NHSCR. Incompleteness of notification may be greater for adults, for whom registration and record linkage may be more difficult. Failures in death notifications occurred mostly because deaths entered on the NHSCR were not notified to the CCRG (3.3%). This incompleteness of notification needs to be taken into account in the interpretation of published studies and in the analysis of studies using NHSCR flagging. It also implies similar incompleteness in published national cancer survival data, which use the same system of flagging. Nevertheless it is a notable achievement that NHSCR has successfully monitored such a high proportion of a population of 50 million people, by entirely clerical procedures, for 40 years. PMID- 1503918 TI - Introduction--cancer in the very young. PMID- 1503919 TI - Neuroblastoma in the very young child: biological considerations. AB - Neuroblastoma is one of the childhood malignancies that frustrates both the clinical and scientist. Clearly, some forms of the disease are relatively benign and the patient can expect to be cured. However, even today, Stage 4 neuroblastoma is one of the childhood malignancies where the overall prognosis remains very poor. Despite extensive investigations into the biology of the disease, little has been gleaned about the underlying causes of the tumour and what truly separates good and poor risk disease. Fortunately, patients under the age of one with neuroblastoma often fall into the good risk group. Many people now believe that neuroblastoma is not just one disease, but several. Some forms of the tumours may, in fact, not be truly malignant. The data that has led to this conclusion and the biological characteristics that are associated with the different forms of the neuroblastoma will be reviewed. In addition, a brief outline of new studies which may identify some of the factors associated with the neuroblasts ability to metastasise will be discussed. PMID- 1503920 TI - Alternative models for early onset of childhood leukaemia. AB - This paper considers theoretical models for early-onset childhood leukaemia. The major focus of attention is the two-hit mutational model. A simple mathematical representation is used to explore mechanisms which might lead to onset of leukaemia at an unusually early age. Two such mechanisms are considered. The first of these, a germinal or very early embryonic first mutation is shown to imply that multiple independent leukaemic clones are likely to arise sequentially in very young patients. Clonal multiplicity could underlie the poor prognosis which has been associated with early onset childhood acute lymphoblastic leukaemia. It implies that curative therapy might require intensive treatment followed by bone marrow rescue to ensure eradication of all single-hit predisposed target cells. The prediction of multiple leukaemic clones might be tested in female patients by means of X-linked restriction fragment length polymorphisms and in patients with B-lineage neoplasms by determination of immunoglobin gene rearrangements. A second mechanism for early onset leukaemogenesis is the occurrence of a high cellular mutation rate in some patients. This is shown to result in leukaemia at significantly earlier age if the mutation rate is sufficiently high to influence target cell loss rate. This mechanism would enable more rapid clonal evolution of leukaemic cells and the early emergence of drug resistant variants. The prediction might be tested experimentally by sequential observation of genetic markers (e.g. Karyotypes, DNA fingerprint patterns) and the rate of emergence of drug resistant phenotypes. Other models, considered more briefly, include one-hit mutational 'dominants' in the developing embryo and faster growth kinetics in neoplasms of younger patients.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1503921 TI - The epidemiology of infant cancers. AB - Cancers in infants represent less than 0.05% of all malignant neoplasms, but form a particularly interesting group for study. The ratio of solid tumours to leukaemias is 2:1 in children aged 1-14 but 5:1 in infants less than 1 year. The rate for neuroblastoma which is the most common malignancy in infants is four times higher in children aged under 1 year than in 1-14 year olds. Other embryonal tumours, e.g. Wilms', heptablastoma and retinoblastoma also show higher rates in infants. The ratios of incidence in males to females differed in a number of instances in the two age groups, e.g. in leukaemias and liver tumours the male to female ratio is greater than one in 1-14 year old children but less than one in infants. These observations suggest that many infant tumours may be aetiologically distinct. Their early onset and predominantly embryonal nature suggest a pre-natal origin and genetic factors may be important. PMID- 1503922 TI - Cytogenetic findings in acute leukaemias of infants. AB - Of 706 children, 528 with acute lymphoblastic leukaemia (ALL) and 178 with acute myelocytic leukaemia (AML), whose leukaemia karyotypes could be successfully analysed, 48 were infants less than 1 year of age, 28 with ALL (5% of ALL patients) and 20 with AML (11% of AML patients). In contrast to older children. ALL-leukaemocytogenetics in infants was characterised by lack of hyperdiploidy with over 50 chromosomes and higher incidence of pseudodiploidy. Thirteen (= 46%) infants had an 11q23 aberration, and 11 of them had t(4;11). In AML, nine (= 45%) infants also had an 11q23 abnormality, e.g. t(9;11). Thus, the 11q23 aberration was present in almost 50% of all leukaemia karyotypes of infants. In ALL of infants, the CALLA negative, pre-pre-B immunophenotype prevailed. In AML of infants, the monocytic subtype dominated. A biphenotypic morphology (lymphoid monocytic) with the expression of lymphoid and myeloid antigens was seen in several ALL and AML cases. In conclusion, leukaemogenesis in infants is a rare event, arising in stem cells of very early hematopoietic differentiation (probably due to gene rearrangement errors, most frequently at FRA11B), and differs from leukaemogenesis in older age groups by unique clinical and cellular features. PMID- 1503923 TI - Disposition of antineoplastic agents in the very young child. AB - Maturation of physiologic process which govern the disposition of pharmacologic agents can yield significant changes in absorption, distribution, metabolism, and elimination of drugs in neonates, infants and children. However, there are very little data concerning the disposition of anticancer drugs in young children. Pharmacokinetic data for six anticancer agents were compared in infants less than 1 year of age and children greater than 1 year of age treated at St Jude Children's Research Hospital. No pharmacokinetic data were available for infants less than 2 months of age. Median methotrexate clearance tended to be lower in four infants (0.26-0.99 years) vs 108 children (1-19 years): 80 vs 103 ml min-1 m 2, respectively (P = 0.01). There was no difference in the median 42 h methotrexate concentration. Teniposide systemic clearance and terminal half-life and cytarabine systemic clearance were not different between the two groups. There was no significant difference in etoposide systemic clearance when normalised to body surface area (ml min-1 m-2), however a significantly lower systemic clearance relative to body weight (ml min-1 kg-1) was observed in two infants, 0.5 to 1 year of age, vs 23 children, 3-18 years of age. Doxorubicin systemic clearance was not significantly different between the two groups when systemic clearance was expressed in ml min-1 kg-1. However, there was a trend toward a lower rate of systemic clearance in ml min-1 m-2 in infants.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1503924 TI - The influence of age on nephrotoxicity following chemotherapy in children. AB - Nephrotoxicity is an important adverse effect of chemotherapy in children. Renal function after treatment with either ifosfamide or cisplatinum in children aged 5 years or less ('younger children') was compared with that in those over 5 years ('older children'). Eighteen children (six younger, 12 older) given ifosfamide were studied after completion of chemotherapy, and 28 patients (16 younger, 12 older) were evaluated after cisplatinum. Glomerular filtration rate was measured from the plasma clearance of 51chromium-labelled edetic acid. Proximal tubular function was assessed by determination of plasma and urine calcium, phosphate, magnesium and glucose concentration; calculations of their fractional excretions, and of the renal threshold for phosphate; and measurement of urinary excretion of beta 2-microglobulin. Distal tubular function was evaluated by measurement of the early morning urine osmolality. Younger children had more severe proximal tubular toxicity than older children treated with ifosfamide, with significantly lower plasma phosphate concentrations and higher fractional excretions of glucose. However, there was no evidence of any such difference in glomerular or distal tubular damage after ifosfamide, and no difference in any aspect of renal function between younger and older children treated with cisplatinum. Increased proximal tubular toxicity after ifosfamide in younger children may have serious implications for future growth and development. PMID- 1503926 TI - Brain and spinal tumours in children aged under two years: incidence and survival in Britain, 1971-85. AB - There were 548 children aged under two with brain and spinal tumours diagnosed during 1971-85 in Great Britain and included in the population-based National Registry of Childhood Tumours. Children aged under two accounted for 12% of all children registered with tumours in these sites. The annual incidence was 25.0 per million. Ependymoma, astrocytoma and medulloblastoma (including primitive neuroectodermal tumour) each accounted for around a quarter of the total. Five year survival rates were 20% for ependymoma, 43% for astrocytoma and 13% for medulloblastoma, each significantly lower than for children aged 2-14 in the corresponding diagnostic group. Mortality in the first year after diagnosis was very high but there were also substantial numbers of later deaths. There was no significant trend in survival rates during the period under review. PMID- 1503925 TI - Toward a cure for infants with brain tumours: the challenge for the 1990's. PMID- 1503927 TI - Leukaemia in the young child. AB - Leukaemia is rare in infancy with an equal predominance of lymphoblastic and myeloblastic cases. Acute lymphoblastic leukaemia in infants under one year is characterised by a high leucocyte count, organomegaly, early B-cell phenotype, sometimes with evidence of monocytoid differentiation and cytogenetic abnormalities. This is reflected in its poor prognosis. The toddler (aged 1-2) tends to develop typical childhood ALL which is responsive to treatment, but remains vulnerable to late effects of therapy, particularly radiation. The distribution of subtypes of AML differs in the younger and older child and results of treatment have improved in all age groups. A uniform strategy appears desirable for all cases of childhood AML. It seems probable that different genetic and environmental factors may be involved in the genesis of infant ALL, childhood ALL and AML in children. The management of leukaemia in children under two poses a considerable challenge. PMID- 1503928 TI - Children under two years treated according to the Medical Research Council UKALL VIII study and trial 1980-1984 (on behalf of the Medical Research Council Working Party on Leukaemia in Childhood). AB - Ten per cent of children entered into the national leukaemia study UKALL VIII were under 2 years at diagnosis. The 6 year event-free survival of this cohort was 39%. Specific adverse features were age under 1 year, high initial white cell count and null cell ALL. Those with common ALL, WBC 10-50 x 10(9) 1-1 and especially those aged 18 months or older did not have an adverse prognosis compared with the whole trial entrants. Overall, however there was a doubling of CNS relapse rate and of both induction and remission deaths. Those with a WBC under 10 x 10(9) 1-1 had a high haematological relapse rate. The type of leukaemia and method of management rather than specifically the age appeared to be the predictor for poor outcome. PMID- 1503929 TI - Acute myelogenous leukaemia in children under 2 years--experiences of the West German AML studies BFM-78, -83 and -87. AML-BFM Study Group. AB - Clinical, morphological, immunological, cytogenetical and prognostic features of 84 children under 2 years of age with AML in studies AML-BFM-78, -83 and -87 were retrospectively analysed. There was a high incidence of acute monoblastic leukaemia (FAB M5) (41 patients--49%) and acute megakaryoblastic leukaemia (FAB M7) (study AML-BFM-87: five patients--13%) in this age group. Acute monoblastic leukaemia was associated with hepatosplenomegaly, extramedullary organ manifestations and chromosomal abnormalities involving 11q23. The probability of an 11-year event-free survival of all patients under 2 years of the three studies combined was 39% (SD 6%). While the event-free survival rates of patients aged 2 years and older could be improved in studies AML-BFM-83 and -87 compared with study AML-BFM-78, overall prognosis in children under 2 years in the three consecutive studies remained unchanged. The event-free survival rate of children with acute monoblastic leukaemia in both age groups was comparable (7 yr-EFS (AML BFM-83 and -87): much less than 2 years--43% (SD 9%), =/much greater than 2 years -33% (SD 9%); P much greater than 0.5). This also applied to other risk groups. In conclusion, taking the high incidence of acute monoblastic and megakaryoblastic leukaemia in children under 2 years into account, no significant differences between children under 2 years or older children concerning response to therapy and overall prognosis could be evaluated. PMID- 1503930 TI - Spontaneous regression of neonatal fibrosarcoma. AB - We report a case of fibrosarcoma, which presented in a two week old boy. Excision was not performed because it would have required mutilating surgery. The tumour regressed and was impalpable by 7 months of age. The patient is tumour free at 4 years of age. This is the first reported case of spontaneous regression of a fibrosarcoma. The literature is reviewed. We conclude that the chances of metastasis are low, tumours are likely to respond to chemotherapy, and mutilating surgery is not appropriate initial treatment for infantile fibrosarcomas. PMID- 1503931 TI - Allogeneic marrow transplantation in the treatment of infants with cancer. AB - Marrow transplantation in infants with cancer present special challenges particularly because of the need to use conditioning regimens containing cytotoxic agents during a period of rapid somatic growth. An up-date of the largest study in children under 2 years of age treated by marrow transplantation for acute myeloblastic leukaemia, and a review of late effects experienced by older children, demonstrate the necessity to develop conditioning regimens which avoid total body radiation. Efforts to achieve this aim in the treatment of leukaemia are summarised. PMID- 1503932 TI - Neonatal soft tissue tumours. AB - Thirty-five different soft tissue tumours occurring in the first month of life are described and classified into five Clinical Groups. A. Excellent prognosis with no treatment or simple surgical excision. B. Good prognosis. Treatment depends upon anatomical site. C. Good prognosis. Treatment usually surgical but chemotherapy may be indicated in certain situations. D. Intermediate prognosis. Treatment as for older child, usually surgery or chemotherapy. E. Poor prognosis. Treatment palliative or experimental. The relatively good prognosis of tumours in this age group and the importance of avoiding over-treatment are emphasised. Treatment guidelines are given and the value of obtaining tissue for biological studies to improve our understanding of these rare tumours is stressed. PMID- 1503933 TI - The evaluation and management of pain in the infant and young child with cancer. AB - In the last decade, there has been a developing awareness of pain in paediatric patients and especially in young patients who may be unable to express their pain. This paper addresses the issue of pain in the infant and young child with cancer. Current understanding of pain and its physiological consequences are explored. Evaluation of pain within a developmental context is outlined. Guidelines are presented for the behavioural and pharmacological management of pain with emphasis on appropriate therapy for the infant and young child. PMID- 1503934 TI - Late effects of early childhood cancer therapy. AB - The late effects of cancer treatment in children diagnosed early in life (under 2 years of age) may be compared to those in children who were over 2 years at the time of diagnosis. Such areas as growth and development (e.g., intellectual and sexual), vital organ function and risk for second cancer are of particular interest. This report reviews late occurring morbidity which was studied in approximately 400 survivors of childhood cancer, 93 of whom were under 2 years of age at diagnosis. The most commonly reported late effect was musculoskeletal in radiation treated patients. More severe cognitive deficits were seen among both age groups cranially irradiated for leukaemia prophylaxis with 24 Gy compared to 18 Gy. Second cancers developed equally between the two age groups. Predisposing factors and/or prior therapy may produce second cancers. There are inherent problems in assessing the outcomes of very young children treated for cancer. Improved survival has only been evident during the last 15 years, a period too short to appreciate many of the end points of interest in adult life. Such patients require a necessarily long follow-up period but this will prove informative in the future as more institutions initiate procedures for extended surveillance. PMID- 1503935 TI - Poor prognosis neuroblastoma: is screening the answer? AB - Neuroblastoma is one of the most common solid tumours of childhood and is unique amongst paediatric cancers in that it results in the urinary excretion of catecholamine metabolites which are easily measured in spot urine samples and so is a condition for which screening may be considered. The continuing poor prognosis associated with late stage disease has stimulated great interest in this proposition. The Japanese have been undertaking pioneering studies of such screening since 1974 and since 1985, all 6 months old babies have been offered screening. Preliminary data would appear to suggest that screening is effective in greatly improving the survival of children with neuroblastoma. However there are difficulties associated with the interpretation of survival data since screening undoubtedly results in the detection of cases which would otherwise have remained 'silent', and the well known problems of lead-time and length-time bias complicate matters still further. The time is not yet ready for universal implementation of screening and further investigation is required. PMID- 1503936 TI - HIV/AIDS. PMID- 1503937 TI - Test for predicting progression to AIDS. PMID- 1503938 TI - Mental health: setting the ball rolling. PMID- 1503939 TI - Learning difficulties: keeping the plates spinning. Interview by Charlotte Alderman. PMID- 1503940 TI - Accident and emergency: the management of hypovolaemic shock. PMID- 1503941 TI - Using education to manage skill mix. AB - The English National Board framework and higher national award for post registration education has at its core the tripartite contract between practitioners, managers and educationalists. For managers the framework offers the potential to develop effective education and training strategies, particularly related to skill mix. By devising a skills matrix based on the ten characteristics of the framework, the author shows how managers can assess the skills required at unit, specialty and individual level. PMID- 1503942 TI - Waking up to safer sex. PMID- 1503943 TI - Uncommon disorders. Summer seasonal affective disorder. PMID- 1503945 TI - Fluid-balance charts. PMID- 1503944 TI - Quality monitoring: its role in purchasing. PMID- 1503946 TI - Psychiatry sidelined. PMID- 1503947 TI - Professional status: automatic autonomy? PMID- 1503948 TI - Sister Susie's column. Reports from the wild side. PMID- 1503949 TI - A day in the life. What do they want--blood? PMID- 1503950 TI - HIV/AIDS. Decision to rule out prosecutions welcomed. PMID- 1503951 TI - The NHS computer revolution. PMID- 1503952 TI - Mental health: invisible arts. PMID- 1503953 TI - Nursing awards: contributing to quality of care. PMID- 1503954 TI - Haemorrhagic brain injury: a care study. AB - Mark was only 20 years old when an unfortunate sequence of events dramatically altered his life. In July 1989 he sustained two subarachnoid haemorrhages within a fortnight, first from a left anterior communicating artery aneurysm and then from a right middle cerebral artery aneurysm. Both aneurysm were successfully clipped but Mark remained hemiplegic with severe physical and behavioural problems, including incontinence, sexual disinhibition, aggression and uninhibited spitting. In November 1989, he was transferred to a neuro rehabilitation unit and his management there will be described, showing how his complex problems were managed within enforced environmental limitations. PMID- 1503955 TI - Alzheimer's disease: does it exist? AB - In posing the question that forms the title of this article, the author seeks not to provide a definitive answer, but to raise the issue in nursing literature. Through this, he suggests, nurses will become aware of the controversy that surrounds the diagnosis, or even existence, of Alzheimer's disease. His objective is to bring the nursing profession more fully into the arena where decisions are made about the future of research into the disease and appropriate strategies for the care of elderly people with dementia. PMID- 1503956 TI - Strategic planning in patient education. AB - Patient education is an important part of health promotion. It can be described as a planned, systematic process designed to influence the behaviour of those who come into contact with the health services. It produces changes in their knowledge, attitudes and the skills required to maintain and improve health. Patient education involves health care professionals in activities which help patients and their relatives learn and incorporate new behaviours into their everyday lives. The author describes a strategic planning tool aimed at achieving this. PMID- 1503958 TI - Promoting open learning systems. PMID- 1503957 TI - Health reforms in New Zealand. PMID- 1503959 TI - Psychiatric nurses reacting to threats to their specialty. PMID- 1503960 TI - Safe practice: machine age killers. PMID- 1503961 TI - Education: criticising 'critical'. PMID- 1503963 TI - Nursing in a critical state. PMID- 1503962 TI - Professionalism: one in the eye for care. PMID- 1503964 TI - A day in the life. Hoe-down at the surgery. PMID- 1503965 TI - Quality: dire care for diabetes. PMID- 1503966 TI - Lateral nursing: cut out the tantrums, nurse. PMID- 1503967 TI - The Sister Susie column. Patients' pop records. PMID- 1503968 TI - Polyphasic taxonomic study of the emended genus Arcobacter with Arcobacter butzleri comb. nov. and Arcobacter skirrowii sp. nov., an aerotolerant bacterium isolated from veterinary specimens. AB - The relationships of 77 aerotolerant Arcobacter strains that were originally identified as Campylobacter cryaerophila (now Arcobacter cryaerophilus [P. Vandamme, E. Falsen, R. Rossau, B. Hoste, P. Segers, R. Tytgat, and J. De Ley, Int. J. Syst. Bacteriol. 41:88-103, 1991]) and 6 reference strains belonging to the taxa Arcobacter nitrofigilis, Arcobacter cryaerophilus, and "Campylobacter butzleri" were studied by using a polyphasic approach, in which we performed DNA rRNA hybridizations, DNA-DNA hybridizations, a numerical analysis of whole-cell protein patterns after sodium dodecyl sulfate-polyacrylamide gel electrophoresis, an analysis of cellular fatty acid compositions, and a phenotypic analysis and determined DNA base ratios. Our results indicate that "C. butzleri" should be transferred to the genus Arcobacter as Arcobacter butzleri comb. nov., as was suggested by Kiehlbauch and coworkers (J. A. Kiehlbauch, D. J. Brenner, M. A. Nicholson, C. N. Baker, C. M. Patton, A. G. Steigerwalt, and I. K. Wachsmuth, J. Clin. Microbiol. 29:376-385, 1991). A rapid screening of all strains in which we used the sodium dodecyl sulfate-polyacrylamide gel electrophoresis technique revealed five major groups, which were identified by using DNA-DNA hybridization data as A. cryaerophilus (two distinct electrophoretic subgroups), A. butzleri, A. nitrofigilis, and a new species, for which we propose the name Arcobacter skirrowii. The phylogenetic position within rRNA superfamily VI was established for each species. A. butzleri strains and strains belonging to one of the electrophoretic subgroups of A. cryaerophilus had similar fatty acid contents. An analysis of fatty acid compositions allowed clear-cut differentiation of all of the other groups. All of the species could be distinguished by using classical phenotypic tests, although erroneous identifications due to a shortage of clear cut differentiating tests could occur. PMID- 1503969 TI - Mycoplasma penetrans sp. nov., from the urogenital tract of patients with AIDS. AB - An unusual mycoplasma, which was isolated from the urine of a human immunodeficiency virus-positive male homosexual patient, has an elongated flask shape and two unique sharply divided internal compartments. The tiplike compartment is densely packed with fine granules, and the body compartment is loosely filled with coarse granules consistent with ribosomal structures. The organism has properties of adherence, hemadsorption, and cytadsorption and invades many different types of mammalian cells. Adhesion and penetration apparently involve the terminally located tiplike structure. Cholesterol is required for growth, and the mycoplasma ferments glucose and hydrolyzes arginine, but does not hydrolyze urea. The results of DNA homology studies revealed that this organism is not genetically related to previously described mycoplasma species that have the same biochemical properties. The results of serologic studies demonstrated that this organism is antigenically distinct from all previously described mycoplasmas. We propose that this new mollicute species should be named Mycoplasma penetrans sp. nov. The type strain is strain GTU-54 6A1 (= ATCC 55252). PMID- 1503970 TI - Enterococcus flavescens sp. nov., a new species of enterococci of clinical origin. AB - Four yellow-pigmented group D enterococci of uncertain taxonomic position were isolated from several humans with severe infections. The results of DNA composition, DNA-DNA hybridization, fatty acid content, and biochemical property studies demonstrated that these organisms were slightly related to other previously described yellow-pigmented enterococcal species and constitute a new species, for which we propose the name Enterococcus flavescens. The type strain of E. flavescens is strain CCM 4239 [corrected]. PMID- 1503971 TI - Genomic fingerprinting by arbitrarily primed polymerase chain reaction resolves Borrelia burgdorferi into three distinct phyletic groups. AB - The causative agent of Lyme disease, Borrelia burgdorferi, was first identified by Burgdorfer et al. in 1982 (W. Burgdorfer, A. G. Barbour, S. F. Hayes, J. L. Benach, E. Grunwaldt, and J. P. Davis, Science 216:1317-1319, 1982) and was isolated by Barbour et al. in 1983 (A. G. Barbour, W. Burgdorfer, S. E. Hayes, O. Peter, and A. Aeschlimann, Curr. Microbiol. 8:123-126, 1983). Since then, a large number of isolates have been collected, and there have been questions regarding the relationships among the various strains. Using genomic fingerprinting by an arbitrarily primed polymerase chain reaction, we resolved into three groups a collection of Eurasian and North American isolates of spirochetes that are generally categorized as B. burgdorferi. Group I strains have been identified in both North America and Eurasia, while strains belonging to Borrelia groups II and III have been found only in Eurasia. These same three groups have also been delineated by Baranton et al. (G. Baranton, D. Postic, I. Saint Girons, P. Boerlin, J.-C. Piffaretti, M. Assous, and P. A. D. Grimont, Int. J. Syst. Bacteriol. 42:370-375, 1992) by independent methods. Two isolates are distinct from all of the other strains in our collection but are clearly members of the genus Borrelia. PMID- 1503972 TI - Legionella shakespearei sp. nov., isolated from cooling tower water. AB - A Legionella-like organism (strain 214T [T = type strain]) was isolated from a cooling tower in Stratford-upon-Avon, England. This strain required L-cysteine and contained cellular branched-chain fatty acids that are typical of the genus Legionella. Strain 214T produced pink colonies on buffered charcoal-yeast extract agar. Ubiquinone Q-12 was the major quinone. Strain 214T was serologically distinct from other legionellae as determined by a slide agglutination test. The results of DNA hybridization studies showed that strain 214T (= ATCC 49655T) is a member of a new Legionella species, Legionella shakespearei. PMID- 1503973 TI - Description of Porphyromonas circumdentaria sp. nov. and reassignment of Bacteroides salivosus (Love, Johnson, Jones, and Calverley 1987) as Porphyromonas (Shah and Collins 1988) salivosa comb. nov. AB - A new species, Porphyromonas circumdentaria, is proposed for pigmented, asaccharolytic strains that were isolated from the gingival margins or mouth associated diseases of cats. This bacterium is an obligately anaerobic, gram negative, brown- or black-pigmented, asaccharolytic, nonmotile, nonsporing, rod shaped organism which does not grow in bile and has a guanine-plus-cytosine content of 40 to 42 mol%. It produces major amounts of acetic, butyric, and isovaleric acids and minor amounts of propionic, isobutyric, and phenylacetic acids as end products of metabolism in cooked meat medium. Glutamate and malate dehydrogenases are present, while 6-phosphogluconate and glucose-6-phosphate dehydrogenases are absent. The major cellular fatty acid is 13 methyltetradecanoic acid (iso-C15:0 acid). P. circumdentaria strains are catalase positive and produce ammonia, and colonies fluoresce under short-wavelength UV light. These strains do not hemagglutinate erythrocytes, exhibit trypsinlike activity, or produce chymotrypsin or alpha-fucosidase. They are heavily piliated and produce a capsule. The type strain is strain VPB 3329 (= NCTC 12469). Bacteroides salivosus (D. N. Love, J. L. Johnson, R. F. Jones, and A. Calverley, Int. J. Syst. Bacteriol. 37:307-309, 1987) is an obligately anaerobic, gram negative, pigmented, asaccharolytic, nonmotile, rod-shaped organism which does not grow in bile and has a guanine-plus-cytosine content of 42 to 44 mol%. This organism produces major amounts of acetic, butyric, and phenylacetic acids and minor amounts of isobutyric and isovaleric acids as end products of metabolism in cooked meat medium.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1503974 TI - Flexibacter ovolyticus sp. nov., a pathogen of eggs and larvae of Atlantic halibut, Hippoglossus hippoglossus L. AB - A psychrotrophic Flexibacter sp., Flexibacter ovolyticus sp. nov., was isolated from the adherent bacterial epiflora of Atlantic halibut (Hippoglossus hippoglossus L.) eggs and was shown to be an opportunistic pathogen for halibut eggs and larvae. The strains which we isolated had the enzymatic capacity to dissolve both the chorion and the zona radiata of the egg shells. A total of 35 isolates were characterized by using morphological and biochemical tests. These strains were rod shaped, gram negative, Kovacs oxidase positive, and pale yellow and exhibited gliding motility. They did not produce acid from any of the wide range of carbohydrates tested. Our isolates had the ability to degrade gelatin, tyrosine, DNA, and Tween 80. Starch, cellulose, and chitin were not degraded. The strains were catalase and nitrate reductase positive, did not produce H2S, and did not grow under anaerobic conditions. F. ovolyticus resembles Flexibacter maritimus, but differs from the latter species in several biochemical and physiological characteristics. DNAs from F. ovolyticus strains had guanine-plus cytosine contents which ranged from 30.3 to 32.0 mol% (strains EKC001, EKD002T [T = type strain], and VKB004), and DNA-DNA hybridization studies revealed levels of relatedness between F. ovolyticus EKD002T and F. maritimus NCMB 2154T and NCMB 2153 of 42.7 and 30.0%, respectively. Compared with previously described Cytophaga and Flexibacter spp. with low guanine-plus-cytosine contents, F. ovolyticus constitutes a new species. Strain EKD002 (= NCIMB 13127) is the type strain of the new species. PMID- 1503975 TI - DNA relatedness among Erysipelothrix rhusiopathiae strains representing all twenty-three serovars and Erysipelothrix tonsillarum. AB - The levels of relatedness among strains of Erysipelothrix rhusiopathiae (serovars 1 through 23 and type N) were estimated by performing DNA-DNA hybridization experiments with the type strains of E. rhusiopathiae and Erysipelothrix tonsillarum, which are the two Erysipelothrix species that have been described. Two distinct DNA relatedness groups were identified. The group 1 strains, representing serovars 1, 2, 4 through 6, 8, 9, 11, 12, 15 through 17, 19, and 21 and type N, exhibited more than 73% hybridization with the type strain of E. rhusiopathiae but less than 24% hybridization with the type strain of E. tonsillarum. Group 2 included serovar 3, 7, 10, 14, 20, 22, and 23 strains, and these strains exhibited more than 66% hybridization with the type strain of E. tonsillarum but less than 27% hybridization with the type strain of E. rhusiopathiae. Strains representing serovars 13 and 18 exhibited low levels of hybridization (16 to 47%) with both of the type strains, indicating that these serovars may be members of a new genomic species. The members of the E. rhusiopathiae and E. tonsillarum groups resembled each other in many phenotypic characteristics, but differed in their ability to produce acid from saccharose and in their pathogenicity for swine. Our results confirm that the genus Erysipelothrix contains two main genomic species, E. rhusiopathiae and E. tonsillarum, which can be differentiated into serovars. PMID- 1503976 TI - Chemotaxonomic differentiation of coryneform bacteria isolated from biofilters. AB - Coryneform bacteria that were isolated from biofilters which are used for waste gas treatment of animal-rendering plant emissions were differentiated and partially identified by using chemotaxonomic methods. On the basis of the results of a numerical analysis of whole-cell fatty acid profiles, 79 isolates were divided into two major groups; the members of the first group contained saturated and monounsaturated fatty acids, whereas the members of the second group were characterized by iso- and anteiso-branched fatty acids. Division into subclusters was based mainly on quantitative differences in fatty acid composition and was confirmed by the results obtained for additional chemical markers (e.g., respiratory quinones, mycolic acids, polar lipids, cell wall amino acids, and whole-cell sugar patterns). By combining the results obtained for chemotaxonomic analyses that were performed for strains containing saturated and monounsaturated fatty acids, we were able to identify the genus Corynebacterium (two Corynebacterium species were differentiated on the basis of the occurrence of tuberculostearic acid), the genus Gordona, and the genus Mycobacterium. Among the strains that produced iso-anteiso fatty acid patterns, one subgroup was affiliated with the "nicotianae" group of the genus Arthrobacter; however, some strains contained a new combination of chemical markers. Peptidoglycan type A4 alpha, L-Lys-Gly-L-Glu was combined with menaquinones MK-7 and MK-8, whereas peptidoglycan type A4 alpha, L-Lys-L-Glu occurred together with MK-8 and MK-9. The second subgroup was characterized by a new type B peptidoglycan and MK-11, as well as small amounts of MK-12. Differentiation that was based first on chemotaxonomy and second on physiology gave reliable results. Thus, coryneform strains with new characteristics were isolated from biofilters. PMID- 1503977 TI - Taxonomic study of the Lactobacillus acidophilus group, with recognition of Lactobacillus gallinarum sp. nov. and Lactobacillus johnsonii sp. nov. and synonymy of Lactobacillus acidophilus group A3 (Johnson et al. 1980) with the type strain of Lactobacillus amylovorus (Nakamura 1981). AB - Biochemical properties and DNA-DNA reassociation studies of Lactobacillus acidophilus strains isolated from humans and animals indicate that these include six genomospecies. Two new species can be differentiated from the established species of the genus Lactobacillus: L. gallinarum sp. nov. (type strain, ATCC 33199) and L. johnsonii sp. nov. (type strain, ATCC 33200). Furthermore, it was clarified that L. acidophilus group A3 (Johnson et al. 1980) is synonymous with L. amylovorus. PMID- 1503978 TI - Tetrazolium [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] reduction by mycoplasmas. AB - We investigated 22 mycoplasma and acholeplasma species for their ability to reduce tetrazolium salts by using the MTT [3-(4,5-dimethylthiazol-2-yl)-2,5 diphenyltetrazolium bromide] assay. The test results were evaluated visually, as well as spectrophotometrically, by using an enzyme-linked immunosorbent assay reader. Our results were very similar to the results obtained when the tetrazolium salt reduction assay described by Aluotto et al. was used. However, the MTT reduction assay appeared to be better because it is faster, more objective and sensitive, easier to evaluate, and less expensive; in addition, it allows quantitative determinations. By using regression analysis a linear correlation between formazan production and the number of colony-forming units was demonstrated for all of the species investigated, indicating that the MTT assay can also be used for growth, toxicity, or chemosensitivity tests for the mycoplasma species that are capable of reducing tetrazolium salts. PMID- 1503979 TI - [Aspects of long-term nursing care of children with spina bifida and hydrocephalus]. PMID- 1503980 TI - [Tasks of the hygiene nurse in the pediatric ward]. PMID- 1503981 TI - [The new social insurance identity card--important tips]. PMID- 1503982 TI - [For child-friendly treatment in pediatric hospitals. Children are children, even when sick]. PMID- 1503983 TI - [Fred Bamatter (1899-1988)]. PMID- 1503984 TI - [Event "Nursing during the war"]. PMID- 1503985 TI - [Prone position--a risk factor for sudden infant death]. PMID- 1503986 TI - [Hermann Mai, 90 years old]. PMID- 1503987 TI - [Nursing shortage in the intensive care unit--on the situation in pediatric cardiac surgery in Germany]. PMID- 1503988 TI - [Hydrocephalus as an associated malformation]. PMID- 1503989 TI - [Student commitment at an oncologic ward]. PMID- 1503990 TI - [A mother's experiences in a pediatric hospital]. PMID- 1503991 TI - [Pediatric nurse in a transit camp--at the same time a contribution to swaddling]. PMID- 1503992 TI - [Commentary on the paper by Christina Klausing on "Swaddling of children in transient camps"]. PMID- 1503993 TI - Detection of drugs in human hair for clinical and forensic applications. AB - While hair has for sometime been analyzed for assessment of trace elements, it is only in recent years that attention has been focused on this matrix as a possible means of evaluating drug impregnation. This technique was applied to treated subjects and drug abusers for determination of drug consumation. The method involved decontamination in ethanol, solubilization in sodium hydroxide at 100 degrees C for 10 min, extraction in chloroform/isopropanol/n-heptane (50:17:33, v/v), separation on a BP-5 capillary column (GC) and detection by mass spectrometry. Hair samples were analysed for barbiturates, antidepressants, benzodiazepines, beta-blockers, nicotine, opiates, benzoylecgonine, cannabis and amphetamines. PMID- 1503994 TI - Technical parameters influencing the severity of injury of front-seat, belt protected car passengers on the impact side in car-to-car side collisions with the main impact between the front and rear seats (B-pillars). AB - Authentic car-to-car side collisions (n = 30) with the main impact area at the B pillar were analyzed to find technical parameters corresponding with the injury severities of the front seat, belt-protected car passengers on the impact side. EES (Energy Equivalent Speed) and delta v (delta v, change in velocity) were highly significant predictors of the severity of thoracic and abdominal injuries and total injury severity coded according to the Abbreviated Injury Scale (AIS). At an EES or delta v greater than or equal to 40 km/h all front-seat car passengers on the impact side sustained a total injury severity of Maximum AIS (MAIS) greater than or equal to 4 and died. Although a passenger could survive the crash without injury to one or more body regions up to the highest EES- and delta v-values, at EES or delta v greater than or equal to 40 km/h fatal injuries were sustained in at least one body region. At an EES greater than or equal to 35 km/h or a delta v greater than or equal to 15 km/h no front-seat car passenger on the impact side remained uninjured. PMID- 1503995 TI - Characterisation of HLA DQ alpha for forensic purposes. Allele and genotype frequencies in British Caucasian, Afro-Caribbean and Asian populations. AB - Allele and genotype frequencies for British Caucasian, Afro-Caribbean and Asian populations were determined for a total of over 600 unrelated individuals at the HLA-DQ alpha locus. These were analysed by polymerase chain reaction amplification of the DNA followed by hybridisation to allele specific oligonucleotide probes in a reversed dot-blot test. Six different alleles were detected and the allele distributions for the 3 populations analysed displayed significant differences. However, the British Caucasian genotypes were statistically very similar to previously published data from US Caucasians as were British Afro-Caribbean genotype frequencies with US Black data. In Caucasians the allele frequencies ranged from 5.2% to 26.9% with a power of discrimination of 0.93. DQ alpha genotype frequencies of Caucasian and Afro Caribbean populations do not deviate from Hardy-Weinberg equilibrium. However, the Asian data displayed significant deviation due to excess homozygotes. PMID- 1503996 TI - Immunohistochemical localization of fibronectin as a tool for the age determination of human skin wounds. AB - We analyzed the distribution of fibronectin in routinely embedded tissue specimens from 53 skin wounds and 6 postmortem wounds. In postmortem wounds a faint but focal positive staining was exclusively found at the margin of the specimens which did not extend into the adjacent stroma. Vital wounds were classified into 3 groups. The first comprising lesions with wound ages ranging from a few seconds to 30 min, the second comprising those with wound ages up to 3 weeks, and the third group with lesions more than 3 weeks old. Ten out of 17 lesions with a wound age up to 30 min showed a clear positive reaction within the wound area. Three specimens in this group were completely negative, while in 4 additional cases the result was not significantly different from postmortem lesions. These 7 cases were characterized by acute death with extremely short survival times (only seconds). In wounds up to 3 weeks old fibronectin formed a distinct network containing an increasing number of inflammatory cells corresponding to the wound age. In 2 cases with a survival time of 17 days and in all wounds older than 3 weeks fibronectin was restricted to the surface of fibroblasts and to parallel arranged fibers in the granulation tissue without any network structures. We present evidence that fibronectin is a useful marker for vital wounds with a survival time of more than a few minutes. Fibronectin appears before neutrophilic granulocytes migrate into the wound area.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1503997 TI - A suicidal death by explosives. AB - A 23-year-old man committed suicide by detonating an explosive substance clutched to his abdomen. The face was singed, the hands were lacerated and the chest and the upper part of abdomen were badly mutilated. The death was due to the destruction of several vital organs. The injuries had a directional nature. Only the consideration of all the facts of the case in relation to the situation, nature, distribution and extent of wounds and the preceding medical and social history allowed a reconstruction of the circumstances. PMID- 1503998 TI - DNA fingerprinting of freeze-dried tissues. AB - DNA profiling is usually unproblematic when carried out on material sampled shortly after death. Prolonged postmortem intervals and improper storage cause significant DNA degradation, however there are instances where DNA analysis becomes necessary months after the autopsy. In such cases the investigator may be able to revert to material initially stored for toxicological purposes. In some cases such specimens undergo freeze-drying before storage. We have therefore tested DNA fingerprinting of freeze-dried postmortem material. It was found that freeze-drying is a suitable method for preserving tissue samples for DNA profiling. PMID- 1503999 TI - Sudden death due to disseminated porocephalosis--a case history. AB - An 18-year-old Nigerian girl died suddenly and unexpectedly from disseminated porocephalosis. The patient was hospitalised complaining of fever, dizziness, weakness and jaundice. Clinical examination revealed a restless, confused and hypotensive patient. She died within two hours of admission. Autopsy revealed disseminated Porocephalus armilatus infestation involving the thoracic and abdominal linings and their internal organs. The relationship between the disseminated parasitic involvement and the death of this girl is discussed. PMID- 1504000 TI - Biostatistical evaluation of blood group, HLA and DNA findings in Jeffreys' immigrant test-case using special kinship and DNA algorithms. AB - In the immigration case cited by Jeffreys et al. (1985), the biostatistical evaluation of blood group findings in 16 systems and of HLA-A,B findings for the mother and child, using a special kinship algorithm developed by Ihm and Hummel (1975), produced a probability of maternity of the Ghanaian-born putative mother of W = 6%; the probability of maternity for her sister was W = 94%. Using the DNA multilocus probes 33.15 and 33.6 and the bandsharing technique, the authors analysed band patterns from the putative mother and child as well as another 3 children of the same woman. It was concluded that the putative mother was the mother of all 4 children. An evaluation of the band patterns using the multi-di allelism model and the kinship algorithm in accordance with the Essen-Moller principle produced: W = 99.99999999999999991%, or, if the "-----" constellations were not considered, W = 99.99998%. PMID- 1504001 TI - Suppression of ischemia-reperfusion injury by liposomal superoxide dismutase in rats subjected to tourniquet shock. AB - To investigate the role of oxygen-derived free radicals in the pathogenesis of tourniquet shock, the authors present an experimental animal model. Two groups of rats were fastened with rubber tubes on both thighs (1.5 kg/cm2) for 6 h under pentobarbital anaesthesia. One group was administered liposomal superoxide dismutase (L-SOD 30,000 U/kg body weight), and the other liposome as a control 3 h prior to tourniquet removal. No rats in the control group (n = 20) survived more than 24 h after reperfusion, whereas 55% of animals treated with L-SOD (n = 20) survived for 24 h or more, and two recovered completely (P less than 0.005). Blood samples were obtained from the abdominal aorta after laparotomy of anaesthetized rats of both groups at different time intervals. Changes in the hematocrit value and blood urea nitrogen during the early periods after reperfusion were attenuated by prior administration of L-SOD, and the total plasma SOD activity of the control animals decreased promptly and continuously throughout the experimental period. This experimental model was very useful to study the pathogenesis of tourniquet shock with respect to reproducibility, induction of the shock stages and mortality. It is thought that oxygen-free radicals are involved in the induction of tourniquet shock, and L-SOD was, to a certain extent, effective against reperfusion injury in the early stages of shock. PMID- 1504002 TI - Formal and population genetic studies of AHSG: further data from Galicia. AB - A sensitive immunodetection method for Alpha-2-HS glycoprotein (AHSG) after ultrathin layer polyacrylamide gel isoelectric focusing has been applied to a family study of 126 matings including 292 offspring. Formal genetic studies are in agreement with an autosomal mode of inheritance for this system. A population study of 506 unrelated individuals from Galicia (NW Spain) gave the following frequencies: AHSG*1 = 0.7559 and AHSG*2 = 0.2441, which correspond to a exclusion chance for non-fathers of 0.1505. PMID- 1504003 TI - Bite injuries upon a newborn. AB - A 2 1/2-year-old boy inflicted on his 7-day-old brother suction and bite injuries of the head with loss of tissue of nose and lips. Place of the incident was the parents' bed. The event motivated us to report on the assignment of such injuries and the reasons for sibling violence. PMID- 1504004 TI - New phenomenon of correlation between measurements errors pertaining to heterozygous DNA profiles. PMID- 1504005 TI - Differential regulation and polyadenylation of transferrin mRNA in Xenopus liver and oviduct. AB - Estrogen destabilizes transferrin mRNA in male Xenopus liver in the same manner as observed for albumin and gamma-fibrinogen. The present study examined estrogen regulation of transferrin gene expression in female Xenopus liver and oviduct. In female Xenopus liver estrogen causes the same enhanced degradation of transferrin mRNA from the cytoplasm as seen in males. In contrast, transferrin is induced 3- to 4-fold in both oviduct nuclear and cytoplasmic RNA. The similar increase in transferrin RNA in both preparations suggests a transcriptional mechanism is responsible for this stimulation. Therefore, transferrin expression is differentially regulated in these tissues by the same hormone. Previous experiments showed that Xenopus serum albumin mRNA has a very short (17 residue) poly(A) tail that may play a role in its hormone-regulated instability. Transferrin mRNA has a similarly short poly(A) tail in liver of both male and female Xenopus. Estrogen has no effect on transferrin polyadenylation in liver. Similarly short poly(A) is found on transferrin mRNA from estrogen-deprived oviducts in explant culture. However, addition of estradiol to the medium results in the appearance of a 50-200 nucleotide poly(A) concurrent with induction. Therefore, transferrin mRNA is differentially polyadenylated in Xenopus liver and oviduct. In the latter tissue polyadenylation is under hormonal control. PMID- 1504006 TI - The metabolic pathways for hormonal steroids appear to be reflected in the stereochemistry of DNA. AB - Computer graphics and energy calculations were employed to examine the relative fit of progesterone and its major biosynthetic precursors and inactive metabolites into partially unwound double stranded DNA. Progesterone was found to be the best fitting molecule; moreover, it was the only compound which exhibited full stereochemical complementarity by inserting completely between base pairs and forming optimal hydrogen bonds with both deoxyribose-phosphate backbones. Intermediates in each step of the biosynthetic and degradation pathways were progressively increasing and decreasing fits into DNA, respectively. When the fits of various possible stereoisomers were examined, the positions of functional groups manifest in the known biosynthetic precursors were found to provide the best possible fitting structures. Conversely, the positions of functional groups of known inactive metabolites provided the worst possible fitting structures. These findings coupled with previous reports showing that the specific biological function assigned to each class of steroid hormone correlates with the formation of a unique pattern of donor/acceptor linkages confirms that hormonal structures are indeed rare in their capacity to form "lock and key" complexes with DNA. Given that all possible linkages to DNA are not yet accounted for, the existence of other naturally occurring compounds with salient biological function is predicted. PMID- 1504007 TI - A Leu----His substitution at residue 93 in human corticosteroid binding globulin results in reduced affinity for cortisol. AB - A steroid binding capacity assay and a radioimmunoassay were both used to measure corticosteroid binding globulin (CBG) in serum samples from 22 patients with sepsis. An approximately 50% discordancy between the two values in one patient suggested the presence of a CBG variant with reduced affinity for cortisol, and this was confirmed by Scatchard analysis. We therefore used the polymerase chain reaction to amplify exons that encode for human CBG from the genomic DNA of this patient. This revealed two mutations within the coding sequences: one of which results in a Leu----His substitution at residue 93 and another which encodes a Ser----Ala substitution at residue 224 of the human CBG polypeptide. To assess the impact of each substitution on the steroid binding affinity of CBG, each mutation was introduced separately into a normal human CBG cDNA, and the normal and mutated cDNAs were expressed in Chinese hamster ovary cells. Scatchard analysis of the CBG produced in culture indicated that the His93 mutation (Kd = 2.24 +/- 1.75 nM) reduced the cortisol binding affinity of CBG (mean +/- SD) significantly (P less than 0.024) when compared to normal CBG (Kd = 0.64 +/- 0.31 nM), while the Ala224 mutation (Kd = 0.63 +/- 0.33 nM) did not influence cortisol binding affinity. We therefore conclude that residue 93 may play an important role in determining the structure of the CBG steroid binding site. PMID- 1504008 TI - Novel antiprogestins Org 31806 and 31710: interaction with mammalian progesterone receptor and DNA binding of antisteroid receptor complexes. AB - We have examined steroid binding parameters and transformation of calf uterine progesterone receptor (PR) liganded with progestins (progesterone and R5020) and the newly synthesized antiprogestins (Org 31806 and 31710). Species specificity analysis indicated that [3H]R5020 binding in the chicken oviduct cytosol could be eliminated in the presence of 100-fold excess radioinert progesterone and R5020 but not Org 31806 and 31710. In the calf uterine cytosol, the progestins and the antiprogestins appeared to interact with the same PR as revealed by the displacement of [3H]R5020 by all of the above steroids. When the extent of [3H]R5020 binding was examined in the presence of different concentrations of radioinert steroids, the relative affinity with which these compounds interacted with the uterine PR was found to be comparable. A 23 degrees C incubation of cytosol transformed the progestin-bound PR complexes increasing their binding to DNA-cellulose from 5 (0 degrees C, nontransformed) to 35%. Under these conditions, 20% Org 31710- and RU486-occupied PR complexes bound to DNA-cellulose whereas only 10% Org 31806-receptor complexes were retained by the resin. Transformation (23 degrees C) of cytosol receptor caused a loss of the larger 8 S form and an increase in the smaller 4 S form. In its unliganded state or when it was complexed with R5020 or the antiprogestins, incubation of PR at 23 degrees C led to dissociation of the receptor-associated 90 kDa heat-shock protein (hsp90). The PR-hsp90 association was stabilized in the presence of 10 mM iodoacetamide when the ligand binding site was occupied by Org 31806 and 31710. The R5020 receptor complexes, however, allowed release of hsp90 under the above transforming conditions. Our results indicate that although Org 31806 and 31710 show no affinity for the avian PR, these steroids interact with the mammalian PR. We propose that the reported antiprogestational effects of Org 31806 and 31710 are mediated via their interaction with PR which appears similar to one that exists between PR and RU486. PMID- 1504009 TI - Properties of a potent LHRH antagonist (Org 30850) in female and male rats. AB - Org 30850 (Ac-D-pClPhe1,2,D-Bal3,D-Lys6,D-Ala10-LHRH) is a novel LHRH antagonist, which is being developed for the treatment of hormone-dependent disorders. The activities of this compound with respect to its endocrinological properties and side-effects were tested in rats and the results were compared with one of the first LHRH antagonists: Ac-D-pClPhe1,2,D-Trp3,D-Arg6,D-Ala10-LHRH (Org 30276). A single subcutaneous (s.c.) dose of 0.3 micrograms/kg Org 30850 administered to rats in pro-estrus gave inhibition of ovulation in approx. 50% of the rats, whereas Org 30276 was approx. 4 times less potent. The effect of a single s.c. injection of Org 30850 on testosterone levels in young adult male rats was also studied. The administration of 250 micrograms/kg or higher of Org 30850 induced a significant decrease in testosterone levels after 3 h, this effect lasted for at least 48 h. Treatment of female rats for 14 days with a daily dose of 12 micrograms/kg Org 30850 decreased statistically significantly uterine and ovarian weights. At a daily dose of 50 micrograms/kg Org 30850 completely suppressed estrous cycles and significantly decreased estradiol and FSH serum levels. The LH levels were below the detection level in both control and treated animals on the (expected) second day of di-estrus. Treatment of male rats for 14 days (25-200 micrograms/kg) resulted in a dose-dependent reduction of the gonads, accessory sex organs, testosterone levels and gonadotrophins. The decrease in gonadal function in both sexes was reversible since the females proved to be as fertile as the controls 6 weeks after the last treatment and an almost complete recovery of the weight of testes, seminal vesicles and ventral prostate was observed in the males 4 weeks after cessation of treatment. In contrast to Org 30276, Org 30850 exerted very slight irritation at the site of injection and no edematous reactions in the extremities at a daily dose of up to 8 mg/kg in male rats. It is concluded that Org 30850 is a very potent LHRH antagonist without edematous reactions and with a more favourable therapeutic index than Org 30276. PMID- 1504010 TI - Identification of an estrogen-binding protein in Pseudomonas aeruginosa. AB - A constitutive estrogen-binding protein (EBP) has been identified in the cytosol of Pseudomonas aeruginosa, a Gram-negative bacterium. All 14 strains tested contained the EBP. Estradiol binding was rapid and maximal binding occurred by 90 min at 0 degrees C. Dissociation of estradiol from the binding protein occurred at a rate of 4.6 fmol/min with a t1/2 of 42 min. EBP binding was destroyed by protease treatment and at high temperature. Sodium molybdate had no effect on binding. The Kd determined by Scatchard analysis was 3.9 nM and the Bmax was 323 fmol/mg protein. The EBP sedimented at 8.9 S on sucrose density gradients. The presence of 0.4 M KCl increased estradiol binding 6-fold but did not cause a shift in the sedimentation value. Gel filtration of the native protein gave an estimated molecular weight of 215,000 and a Stokes radius of 50.2 A. Steroid binding specificity, in order of decreasing affinity, was estradiol, estrone, dihydrotestosterone, estriol, testosterone, progesterone and promegestone. Other steroid hormones tested did not compete for estradiol binding. Identification of an EBP in a bacterium allows a comparative analysis of other steroid-binding proteins in unicellular microorganisms. PMID- 1504011 TI - The influence of NADPH-dependent lipid peroxidation on the progesterone biosynthesis in human placental mitochondria. AB - In an in vitro system consisting of human term placental mitochondria and an NADPH-generating system plus Fe2+, significant lipid peroxidation was observed along with a concomitant inhibition of progesterone biosynthesis. This inhibition could be markedly blocked by Mn2+, superoxide dismutase and dimethylfuran, inhibitors of NADPH-dependent lipid peroxidation. In addition, it has been found that malondialdehyde formation is accompanied by a corresponding decrease in placental mitochondrial cytochrome P-450 content. Inhibitors of lipid peroxidation also prevent the loss of cytochrome P-450, further demonstrating a direct relationship between NADPH-dependent lipid peroxidation and degradation of cytochrome P-450 in cell-free systems. These measurements provide the first evidence that the inhibition of progesterone biosynthesis by a NADPH-dependent lipid peroxidation in placental mitochondria is a consequence of cytochrome P-450 degradation due to lipid peroxidation. PMID- 1504012 TI - Glucocorticoid-recognizing and -effector sites in rat liver plasma membrane. Kinetics of corticosterone uptake by isolated membrane vesicles--I. Binding and transport. AB - To gain insight into the mechanisms governing cellular uptake of glucocorticoids, we studied the binding and membrane transport of corticosterone (B) on a highly purified plasma membrane fraction from rat liver that was homogenized using a gentle, isotonic procedure. The fraction was mostly in the form of right-side out and osmotically active vesicles that were free of intracellular glucocorticoid receptors (GCR), transcortin (CBG) and ATP. Our uptake and binding studies carried out at 22 degrees C with [3H]B in physiological concentrations resulted in the following findings: (1) unlabeled B competed with [3H]B for uptake by the membrane vesicles; half-maximal competition of specific uptake was achieved with a 10- to 11-fold molar excess of unlabeled B. (2) [3H]B uptake was a saturable process of unusual kinetics (multiple sigmoidity); modified Scatchard plots revealed three significantly different apparent Kd-values of 1.3, 4.7 and 17.3 nM, corresponding to free B in the blood of non-stressed rats (4-16 nM). (3) Osmotic shrinkage of the vesicles led to a linear decrease in specific uptake, while non-specific uptake was independent of vesicle volume. Passive diffusion of [3H]B took place in leaky, but not in intact, vesicles. Reversible binding to, and mediated transport through, the membrane were interdependent parts of a strongly linked process. B was accumulated inside the vesicle up a concentration gradient by an active transport that followed first-order kinetics (Kt:3.9 nM); for its statistically reliable mathematical formulation and kinetic analysis, a replot was developed that revealed that relative accumulation increased with decreasing external hormone concentration. (4) Comparative binding studies disclosed that the apparent Kd-values (86.5 +/- 7.3 and 77.0 +/- 14.3 nM, respectively) of the [3H]B interactions with CBG and GCR did not differ (P greater than 0.3). These findings permit the conclusion that a plasma membrane inserted carrier for B, effectively operating at physiological concentrations in the blood, is involved in a functional and regulatory manner in the biological action of glucocorticoids. PMID- 1504013 TI - Glucocorticoid-recognizing and -effector sites in rat liver plasma membrane. Kinetics of corticosterone uptake by isolated membrane vesicles--II. Comparative influx and efflux. AB - To elucidate the initial step in the interaction between glucocorticoids (GC) and the hepatocyte, we examined at 22 degrees C further kinetic properties of active corticosterone (B) transport mediated by a putative, plasma membrane-inserted carrier for GC (GCC) as previously reported [Allera and Wildt, J. Steroid Biochem. Molec. Biol. 42 (1992) 737-756]. We used a purified, well-characterized, osmotically active vesicle fraction of plasma membrane (PM), free of ATP, isolated from rat liver and a method developed by us to describe transport processes mathematically: (1) uptake (U) of 7 nM B into the vesicles (influx, I) occurred very rapidly whereby T1/2 = 8.3 s, the time (S) required for half maximum transport; the influx velocity (dU/dS = V) decreased degressively with time following second-order kinetics characterized by an initial transport V (VT0) of 177.7 fmol/mg membrane protein/s. (2) VToI of B-influx rose with temperature biphasically (P less than 0.025): activation energy above and below 15 degrees C (at PM phase transition) amounted to 9.5 and 26.5 kJ/mol. Neither at 45 nor at 60 degrees C did transport take place, revealing the high thermolability of GCC. (3) Efflux (E) of 6.5 nM B, i.e. transport out of the vesicles preincubated with the steroid, showed that influx had resulted in a 19.6 fold intravesicular hormone accumulation, indicating active ("uphill") transport. (4) The efflux velocity (dE/dS = V) exhibited almost the same kinetic quality as that of influx: it decreased following mainly second-order kinetics whereby T1/2 = 8.0 s. However, its whole time-course was much slower and the VT0 of efflux (VToE) was 6.3 lower than VToI. (5) Using physics and thermodynamics, we deduced that the affinity (AF) between B and GCC is proportional to the square of VT0. (6) Thus, because AF approximately (1/6.3)2, AF of the B-GCC interaction after completion of influx was calculated to be 40 times lower (Kd = 708 nM; delta G degrees = -34.9 kJ/mol) than at outset of influx, whereby delta G degrees = -44.0 kJ/mol. Concluding from these and previous findings, we present a new hypothesis on B transport into the hepatocyte: There is no difference (P greater than 0.3) in free enthalpy between transcortin (CBG) and the intracellular GC receptor interacting with B (delta G degrees = -40.1 and -40.4 kJ/mol). The GCC, however, is characterized by its ability to switch from a high- to lower-affinity when interacting with B (and vice versa due to metabolic energy input).(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1504014 TI - Changes in plasma testosterone levels during the peri-hatching period in the chicken. AB - Blood was obtained by heart puncture from 19-day-old Black Sex link chicken embryos and from Black Sex link chickens at 1.5, 6, or 24 h post-hatching. Plasma testosterone was determined by gas chromatography-mass spectrometry associated with stable isotope dilution. At 19 days the plasma of male and female chick embryos contains measurable amounts of testosterone and levels do not differ between sexes. After hatching plasma testosterone gradually declines from pre hatch concentrations in males and females, but in all the post-hatch ages studied, plasma testosterone was significantly higher in male than in female chicks. These results indicate that in male chickens, contrary to mammals at birth, there is no surge in plasma testosterone at hatching. PMID- 1504015 TI - Transforming growth factor beta modulates phosphorylation of the epidermal growth factor receptor and proliferation of A431 cells. AB - Transforming growth factor beta (TGF-beta) increased the phosphorylation of the epidermal growth factor (EGF) receptor and inhibited the growth of A431 cells. Incubation with TGF-beta induced maximal EGF receptor phosphorylation to levels 1.5-fold higher than controls. Phosphorylation increased more prominently (4-5 fold) on tyrosine residues as determined by phosphoamino acid analysis and antiphosphotyrosine antibody immunoblotting. The kinase activity of EGF receptor was also elevated 2.5-fold when cells were cultured in the presence of TGF-beta. The antiproliferative effect of TGF-beta on A431 cells was accompanied by prolongation of G0-G1 phase and by morphological changes. TGF-beta augmented the growth inhibition of A431 cells which could be induced by EGF. In parallel, the specific EGF-induced increase in total phosphorylation of the EGF receptor was also augmented in the presence of TGF-beta. In cells cultured with TGF-beta, the phosphorylation of EGF receptor tyrosines induced by 20-min exposure to EGF was further increased 2-3-fold, suggesting additive effects upon receptor phosphorylation. EGF receptor activation by TGF-beta is characterized by kinetics quite distinct from that induced by EGF and therefore appears to take place through an independent mechanism. The TGF-beta-induced elevation in the phosphorylation of the EGF receptor may have a role in the augmented growth inhibition of A431 cells observed in the presence of EGF and TGF-beta. PMID- 1504016 TI - Stability of retinoblastoma gene expression determines the tumorigenicity of reconstituted retinoblastoma cells. AB - Mutational inactivation of the retinoblastoma gene (RB) is an invariant feature of the childhood eye cancer retinoblastoma and of tumor cells derived therefrom. In a previous study, retrovirus-mediated transfer of wild-type RB into cultured retinoblastoma cells resulted in a marked enlargement and reduced growth rate of these cells, as well as loss of their tumorigenic properties in nude mice. It was therefore difficult to separate the proposed growth-suppressing and tumor suppressing activities of RB protein. Here, we show that clones of RB reconstituted retinoblastoma cells can be isolated that stably express apparently normal RB protein for at least 20 months of continuous culture. These clones were indistinguishable from nonreconstituted cells by multiple parameters including morphology, growth rate, and cell cycle distribution. Despite similar phenotypes in culture, clones with stable RB expression were uniformly nontumorigenic in nude mice, whereas those that lost such expression regained their tumorigenic properties. These results indicate that the tumorigenicity of these cells is entirely determined by the presence or absence of exogenous RB protein expression and that suppression of tumorigenicity is distinct from inhibition of cellular growth in culture. PMID- 1504017 TI - Inducible transformation of cells from transgenic mice expressing SV40 under lac operon control. AB - If it were possible to clone in vitro cells of any type, at any stage of differentiation, from an extensively characterized animal such as the mouse, many areas of cell biology would benefit. Indeed, it would be even more helpful if these cells could subsequently be restored to their normal in vivo phenotype whenever required. Here, we describe a step on the pathway to such an idealized "clonable" mouse. In principle, it seeks to link a "universal" transforming agent to a regulatory system that is relatively simple, yet quite foreign to the mouse. A plasmid containing the bacterial lac operator/promoter region linked to the SV40 large T antigen and a vector containing the lac repressor that can be expressed in mammalian cells were coinjected into fertilized mouse oocytes utilizing the standard techniques for generating transgenic mice. Two progeny were obtained that express large T antigen in the presence, but not the absence, of the nonmetabolizable lac inducer, isopropyl-beta-thio-D-galactoside. This report characterizes fibroblast cell lines established from these transgenics that are readily transformed in vitro with isopropyl-beta-thio-D-galactoside. A significant proportion of the cells are restored to their "normal" (nontransformed phenotype) when isopropyl-beta-thio-D-galactoside is removed. PMID- 1504018 TI - Erks: their fifteen minutes has arrived. AB - In conclusion, a multigene family (ERK) encoding protein kinases that have the capacity to convert tyrosine kinase signals to serine/threonine phosphorylation signals has been identified in animal and yeast cells. Protein kinases from this family have been shown to be phosphorylated on tyrosine and threonine in response to mitogens, as well as to have the capacity to autophosphorylate on these amino acid residues. In contrast, they apparently phosphorylate exogenous substrates on serine and/or threonine. Studies with cultured cells, Xenopus, and sea star oocytes have furthered our understanding of possible functions of Erks in vivo. These enzymes respond immediately to extracellular signals and are involved in G0 G1 transition (cultured cells), as well as in the M phase of oocyte maturation (Xenopus and sea star oocytes). Their usage of MAPs as substrates in vivo suggests a possible role of Erks in microtubule reorganization. ERK-encoded protein kinases use c-Jun, EGF receptor, and Raf-1 as potential substrates and can also reactivate dephosphorylated S6 kinase in vitro. Taken together, these data suggest that these enzymes play an important role in relaying the mitogenic signal by phosphorylating down-stream kinases and specific transcriptional factors, as well as having possible feedback function in the process of signal transduction. The results from the study of the yeast enzymes are pertinent to Erk activation in cells with nonmitogenic responses described above. In such cases, Erk protein kinases may act directly or indirectly on cyclins to arrest division and permit differentiation. The pathways influenced by ERK-like gene products in animal and yeast cells suggest that, depending on the downstream targets of substrates, transcriptional changes in a particular cell may occur to drive the cell cycle or, alternatively, withdrawal from the cell cycle may lead to specific differentiation events.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1504019 TI - Discordant transforming growth factor beta 1 RNA and protein localization during chemical carcinogenesis of the skin. AB - Transforming growth factor beta (TGF-beta) inhibits proliferation of normal keratinocytes, and this response is retained, to variable extents, in benign tumors of the skin (S. Haddow, D. J. Fowlis, K. Parkinson, R. J. Akhurst, and A. Balmain, Oncogene, 6: 1465-1470, 1991). To investigate the profile of TGF-beta biosynthesis during various stages of chemical carcinogenesis of the skin, we used a combination of ribonuclease protection assay, in situ hybridization with gene-specific probes for TGF-beta 1, -beta 2, and -beta 3, and immunohistochemistry with isoform-specific antibodies against TGF-beta 1. Following 12-O-tetradecanoylphorbol-13-acetate treatment of adult mouse skin, there was a rapid induction of TGF-beta 1 protein. Intracellular TGF-beta 1 protein was localized to suprabasal keratinocytes, and the extracellular form was localized predominantly to the dermis. Despite ubiquitous induction of TGF-beta 1 protein by 12-O-tetradecanoylphorbol-13-acetate in various mouse strains, we noted strain-specific differences in the quantitative induction of TGF-beta 1 RNA. Papillomas and carcinomas induced in vivo had elevated levels of TGF-beta 1 RNA within the basal keratinocyte compartment but did not contain significant levels of TGF-beta 1 protein within the tumor. We postulate that the tumor evades TGF-beta 1-controlled negative growth regulation by altered translational and/or posttranslational processing mechanisms of this growth factor. Levels of TGF-beta 2 and -beta 3 RNA were not elevated at any stage of chemical carcinogenesis of the skin. PMID- 1504020 TI - Evoked potential and psychophysical analysis of Fourier and non-Fourier motion mechanisms. AB - Some visual stimuli produce a strong percept of motion, even though they fail to excite motion detectors based on Fourier energy or cross correlation. Models which suffice to explain the motion percept in these non-Fourier motion (NFM) stimuli include linear spatiotemporal filtering, followed by rectification, followed by standard motion analysis (Chubb & Sperling 1988). We used the human "motion-onset" evoked potential, which has been assigned to area 17 on the basis of work in the macaque (van Dijk et al., 1986; van Dijk & Spekreijse, 1989), to investigate the neural substrate of the processing stages postulated in the above models. Motion-onset VEPs elicited by FM and NFM matched for spatial and temporal characteristics were indistinguishable in temporal characteristics and scalp topography at a transverse chain of electrodes. Addition of textural cues (granularity and higher-order form) did not influence the response dynamics or scalp topography of NFM responses. However, comparison of responses to NFM stimuli and related stimuli without coherent motion but similar spatial and temporal properties showed that the motion-onset responses were distinct from responses to the onset of fixed flicker-defined contours not undergoing coherent motion. We discuss the implications of these results for computational models of motion analysis. PMID- 1504021 TI - Visual receptor cycle in normal and period mutant Drosophila: microspectrophotometry, electrophysiology, and ultrastructural morphometry. AB - Visual pigment, sensitivity, and rhabdomere size were measured throughout a 12-h light/12-h dark cycle in Drosophila. Visual pigment and sensitivity were measured during subsequent constant darkness [dark/dark (D/D)]. MSP (microspectrophotometry) and the ERG (electroretinogram) revealed a cycling of visual pigment and sensitivity, respectively. A visual pigment decrease of 40% was noted at 4 h after light onset that recovered 2-4 h later in white-eyed (otherwise wild-type, w per+) flies. The ERG sensitivity [in w per+ flies in light/dark (L/D)] decreased by 75% at 4 h after light onset, more than expected if mediated by visual pigment (MSP) changes alone. ERG sensitivity begins decreasing 8 h before light onset while decreases in visual pigment begin 2 h after light onset. These cycles continue in constant darkness (D/D), suggesting a circadian rhythm. White-eyed period (per) mutants show similar cycles of visual pigment level and sensitivity in L/D; per's alterations, if any on the D/D cycles were subtle. The cross-sectional areas of rhabdomeres in w per+ were measured using electron micrographic (EM) morphometry. Area changed little through the L/D cycle. PMID- 1504022 TI - Microspectrophotometric determinations of rod visual pigments in some adult and larval Australian amphibians. AB - Visual pigments from the red rods of adults of eight species of Australian anuran amphibians, from a variety of habitats, were analyzed by microspectrophotometry. The lambda max in all cases fell between 502 nm and 506 nm, and the absorption spectra were well fitted by an A1-based visual pigment template curve. Red rod pigments were also analyzed for a number of tadpoles. In some cases the data were best fitted with an A1-based visual pigment template, in other cases with an A2 based template, and finally some tadpoles appeared to have mixtures of the two pigments. PMID- 1504023 TI - Binocular rivalry suppression disrupts recovery from motion adaptation. AB - The motion aftereffect (MAE) lasts longer when the test period does not immediately follow adaptation, a phenomenon called storage. Does storage of the MAE occur if the test target is present but rendered phenomenally invisible owing to the presence of a rival target presented to the other eye during the storage period? Our experiment addressed this question. Following adaptation to a drifting grating, an intervening period preceded testing with a stationary grating. During this period, the adapted eye either viewed the test target immediately or was occluded, and the unadapted eye either viewed a high-contrast rival target or was occluded. Thus four conditions were employed. The duration of the residual MAE was found to be longer for the rivalry condition (grating and rival target viewed) than for the normal MAE condition (grating viewed), and comparable to that in the stored MAE condition (both eyes occluded). Thus, the MAE is stored when the test target is rendered invisible due to binocular rivalry, indicating that a suppressed target is ineffective at promoting decay of the MAE. So while suppression does not prevent information about the adapting grating from reaching the site of generation of the MAE (Lehmkuhle & Fox, 1975), it can prevent information about the test target from reaching the site of the stored MAE. Current models attribute the MAE to reduced responsiveness of direction-selective cortical neurons (Sutherland, 1961; Barlow & Hill, 1963). Thus, storage should reflect a differential return of these adapted cells to preadapted response levels, dependent on postadaptation stimulation.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1504024 TI - A breakdown of the blood-brain barrier is associated with optic nerve regeneration in the frog. AB - We have examined the integrity of the blood-brain barrier during optic nerve regeneration in the frog Litoria (Hyla) moorei using rhodamine B-labeled bovine serum albumin (RBA). A transient localized breakdown of the blood-brain barrier was observed between 1 and 5 weeks after extracranial optic nerve crush. The zone of breakdown progressed along the experimental optic nerve, ascended the opposite optic tract, and swept rostro-caudally across the tectum contralateral to the crushed nerve. By 7 weeks, the blood-brain barrier was once again intact along the length of the optic pathway. In a concurrent series of frogs, regenerating optic axons were visualized by anterograde transport of horseradish peroxidase (HRP). At each stage examined, the region reached by the front of regenerating axons corresponded to that in which the blood-brain barrier had been shown to break down. In contrast to the results after nerve crush, the blood-brain barrier remained intact along the length of the optic pathway following optic nerve ligation to prevent regeneration. We conclude that the breakdown of the blood brain barrier which occurs during optic nerve regeneration in the frog is triggered by the regenerating axons. PMID- 1504025 TI - Visual deprivation fails to reduce calbindin 28kD or GABA immunoreactivity in the rhesus monkey superior colliculus. AB - Antibody labeling of the calcium-binding protein calbindin 28kD (CaBP) and gamma aminobutyric acid (GABA) is altered by short-term monocular deprivation in the lateral geniculate nucleus and visual cortex of adult primates. It is not known whether these alterations occur in other subcortical visual structures. We therefore have examined antibody labeling to CaBP and GABA in the superior colliculus (SC) of visually deprived Rhesus monkeys. One group was monocularly enucleated as adults. The other monkeys experienced different types of monocular and binocular deprivation from birth, including occlusion of one eye, and/or surgically induced aphakia, optically corrected with extended-wear contact lenses, or an intraocular lens implant. Some of these monkeys also had one eye enucleated prior to perfusion. In the SC of normal monkeys, CaBP-immunoreactive neurons formed three laminar tiers within SC, one within the zonal layer (ZL) and upper superficial gray layer (SGL), another bridging the optic and intermediate gray layers, and a third within the deep gray layer. CaBP neurons within the upper tier had small pyriform or stellate morphologies while those in the deeper tiers were slightly larger neurons, most with a stellate morphology. GABA immunoreactive neurons were densely distributed within the SGL and more sparsely distributed within the deeper layers. These cells were mostly small neurons with horizontal, pyriform, or stellate morphologies. Neither monocular enucleation nor occlusion nor aphakia combined with continuous occlusion of the fellow eye produced any visible reduction in antibody labeling in cells or neuropil within the SC. Full-field measures of labeling intensity (optical density) within the ZL and upper SGL revealed no consistent differences between the SC contralateral or ipsilateral to the affected eye in either CaBP- or GABA-labeled sections. Measures of the optical density, number, and size of labeled neurons also showed no consistent effects of enucleation and/or occlusion. We therefore conclude that the retino-geniculostriate and retino-collicular systems differ in their response to deprivation which is likely due to the significant overlap of retinal axons from the two eyes that occurs in the SC of the Rhesus monkey. PMID- 1504026 TI - Packing geometry of human cone photoreceptors: variation with eccentricity and evidence for local anisotropy. AB - Disorder in the packing geometry of the human cone mosaic is believed to help alleviate spatial aliasing effects. To characterize cone packing geometry, we gathered positions of cone inner segments at seven locations along four primary and two oblique meridians in an adult human retina. We generated statistical descriptors based on the distribution of distances and angles to Voronoi neighbors. Parameters of a compressed-jittered model were fit to the actual mosaic. Local anisotropies were investigated using correlograms. We find that (1) median distance between Voronoi neighbors increases with eccentricity, but the minimum distance is constant (6-8 microns) across peripheral retina; (2) the cone mosaic is least compressed and jittered at the edge of the foveal rod-free zone; (3) disorder in the foveal center resembles that described by Pum et al. (1990); (4) cone spacing is 10-15% less in one direction than in the orthogonal direction; and (5) cone spacing is greater in the radial direction (along meridians) than in the tangential direction (along lines of isoeccentricity). The nearly constant minimum distance implies that high spatial frequencies may be sampled even in peripheral retina. Local anisotropy of the cone mosaic is discussed in relation to the growth of the primate retina during development and to the orientation biases of retinal ganglion cells. PMID- 1504027 TI - Normalization of cell responses in cat striate cortex. AB - Simple cells in the striate cortex have been depicted as half-wave-rectified linear operators. Complex cells have been depicted as energy mechanisms, constructed from the squared sum of the outputs of quadrature pairs of linear operators. However, the linear/energy model falls short of a complete explanation of striate cell responses. In this paper, a modified version of the linear/energy model is presented in which striate cells mutually inhibit one another, effectively normalizing their responses with respect to stimulus contrast. This paper reviews experimental measurements of striate cell responses, and shows that the new model explains a significantly larger body of physiological data. PMID- 1504028 TI - Functional binocular vision is not dependent on visual experience in the praying mantis. AB - In vertebrates, it has been shown that binocular visual experience is necessary to develop normal spatial vision. We have investigated whether this is also true for an invertebrate, the praying mantis. The praying mantis is a predatory insect in which prey localization involves the use of binocular disparities. We raised mantids which had one eye occluded throughout development and tested monocular visual fixation and binocular distance estimation in the adult animals. The results revealed that both fixation and prey catching behavior were normally functional in the monocularly reared animals. Thus we conclude that, in mantids, binocular vision is based on a fixed mode of development. PMID- 1504029 TI - NADPH-diaphorase reactivity in the ventral and dorsal lateral geniculate nuclei of rats. AB - The present study describes the patterns of NADPH-diaphorase reactivity in the ventral and dorsal lateral geniculate nuclei of rats. In the ventral lateral geniculate nucleus, two distinct populations of NADPH-diaphorase reactive cells are apparent. One population is deeply stained, generally larger in somal size and located in the more superficial or dorsolateral regions of the nucleus. The second population of reactive cells in the nucleus is lightly labeled, small in somal size, and found in deeper or more ventromedial regions of the nucleus. Double labeling with an antibody to GABA revealed that neither cell class is GABAergic. In the dorsal lateral geniculate nucleus, reactivity is apparent in lightly labeled small cells only, most of which are GABA immunoreactive also. The NADPH-diaphorase reactive cells, however, form only a small proportion of the total population of GABAergic cells in the nucleus. The striking feature of the NADPH-diaphorase reactive cells in the dorsal lateral geniculate nucleus is their spatial distribution. Most cells are located in the more superficial or dorsolateral areas: very few are apparent in deeper or more ventromedial areas of the nucleus. This distribution closely parallels the location of the outer "shell" region of the nucleus (see Reese, 1988), which receives most of its afferents from the smaller class II and III ganglion cells of the retina and from the superior colliculus. PMID- 1504030 TI - The assessment of maritally violent men on the California Psychological Inventory. AB - This study assessed 87 maritally violent men (MV), 42 maritally nonviolent, maritally discordant men (NVD), and 48 maritally nonviolent, maritally satisfied men (NVS) on the California Psychological Inventory (CPI), a test of the normal personality. A MANOVA and subsequent range tests indicated that the NVD and NVS groups had significantly higher scores than the MV group on 10 of the 18 subscales: Responsibility, Socialization, Self-Control, Tolerance, Achievement via Conformance, Achievement via Independence, Good Impression, Intellectual Efficiency, and Psychological Mindedness. A discriminant analysis contrasting the MV group with the combined NVD and NVS group correctly classified 68% of the subjects and accounted for 20.94% of the variance between groups. Along with previous findings, the data indicated that maritally violent males exhibit different personality characteristics than maritally nonviolent men in three general areas: intimacy, impulsivity, and problem-solving skills. Many of these problem areas were significantly correlated with childhood violence experiences. PMID- 1504031 TI - Patterns of socially desirable responding among perpetrators and victims of wife assault. AB - Wife assaulters attending a treatment group and women who had just exited an abusive relationship were asked to report on the extent of physical violence and emotional abuse in their relationship. Measures of socially desirable responding (SDR) were administered to both groups. Wife assaulters' self-reports of physical abuse correlated negatively with one SDR measure (the Balanced Inventory of Desirable Responding) but not another (the Marlowe-Crowne Social Desirability Scale); emotional abuse correlated negatively with both measures. Although physical abuse was primarily related to impression management, psychological abuse was affected by both impression management and self-deception aspects of SDR. Wife assaulters' reports of their own anger also correlated negatively with SDR. Both self-deception and impression management appear to contribute to underreporting of anger. Finally, abuse victims' reports of both physical and emotional abuse were unrelated to SDR. PMID- 1504032 TI - Dating violence, social learning theory, and gender: a multivariate analysis. AB - The study of violence between dating partners is a logical extension of interest in marital violence. However, little of this research tests explanations of intimate violence using multivariate techniques, and only recently have such tests occurred within a theoretical framework. Drawing on a recent social learning model of courtship violence (Riggs & O'Leary, 1989), this paper empirically examines constructs hypothesized to be predictive of the use of dating violence and investigates possible gender differences in the underlying causal structure of such violence. Logit analysis indicates that parent-child violence, drug use, and knowledge of use of dating violence by others predict the use of courtship violence by females. Belief that violence between intimates is justifiable, drug use, and parental divorce are related to perpetration of dating aggression by males. Explanations for these results and the importance of a multivariate approach to the problem are discussed. PMID- 1504033 TI - A structural model examining the relationship between physical child abuse, sexual victimization, and marijuana/hashish use in delinquent youth: a longitudinal study. AB - A structural model of the relationships among physical abuse and sexual victimization experiences, marijuana/hashish use (measured by self-report and urine test data) and self-reported delinquent behavior (theft crimes, index offenses, crimes against persons, drug sales and total delinquency) over time was tested in a longitudinal study of juvenile detainees. The hypothesized model was supported by the data. Theoretical, research and policy implications of the results are drawn. PMID- 1504034 TI - The nuts and bolts of implementing large-scale longitudinal studies. AB - Studies that assess large numbers of subjects for longitudinal research, for epidemiological purposes, or for the evaluation of prevention and intervention efforts, are very costly and should be undertaken with the greatest care to ensure their success. The success of a study, apart from its scientific merit, depends largely on the ability of the researcher to plan and set up a smoothly running operation. However, the skills required for such a task are often not acquired in academic training, nor do scientific journals abound with information on the practical aspects of running a large study. This paper summarizes the experience gained in executing a longitudinal study and covers aspects of planning, hiring of staff, training and supervision of interviewers, data collection and data entry and management. The importance of the use of the computer as a management tool is stressed. PMID- 1504035 TI - Recruiting nonviolent men as control subjects for research on marital violence: how easily can it be done? AB - Data regarding the prevalence of violence among subjects recruited for nonviolent control groups in five studies are presented. These studies examined subjects recruited using a variety of methods, including couples seeking marital therapy and couples recruited from newspaper advertisements. Across the studies, it appears that up to one-third of maritally nondistressed couples and one-half of maritally distressed couples report that husband violence has occurred in their relationship. The implications of these data for the recruitment of control groups in future studies of marital violence are discussed, and questions regarding the ease of recruiting nonviolent couples for control groups are raised. PMID- 1504036 TI - Monomer units for the beta-bend ribbon structure: MeAib peptides. AB - A conformational analysis in CDCl3 solution by using i.r. absorption and 1H nuclear magnetic resonance spectroscopy was performed on the fully blocked dipeptides Z-MeAib-Aib-NHMe, Z-MeAib-L-Ala-NHMe, Z-Aib-MeAib-NHMe, and Z-L-Ala MeAib-NHMe, representing repeating units of the beta-bend ribbon spiral (an approximate 3(10)-helix, with an intramolecular H-bonding donor every two residues), where Z represents benzyloxycarbonyl, MeAib alpha methylaminoisobutyric acid, and NHMe methylamino. The molecular and crystal structures of the first three compounds were also assessed by X-ray diffraction. While the -MeAib-Aib-, -MeAib-L-Ala-, and -Aib-MeAib- sequences give stable beta bend structures, the preferred conformation of the -L-Ala-MeAib- sequence is open. These results indicate that the MeAib residue is a good beta-bend promoter, but less efficient than its unmethylated counterpart at position i + 2. PMID- 1504037 TI - Modes of binding of alpha (1-2) linked manno-oligosaccharides to concanavalin A. AB - Three-dimensional structures of the complexes of concanavalin A (ConA) with alpha(1-2) linked mannobiose, triose and tetraose have been generated with the X ray crystal structure data on native ConA using the CCEM (contact criteria and energy minimization) method. All the constituting mannose residues of the oligosaccharide can reach the primary binding site of ConA (where methyl-alpha-D mannopyranose binds). However, in all the energetically favoured complexes, either the non-reducing end or middle mannose residues of the oligosaccharide occupy the primary binding site. The middle mannose residues have marginally higher preference over the non-reducing end residue. The sugar binding site of ConA is extended and accommodates at least three alpha(1-2) linked mannose residues. Based on the present calculations two mechanisms have been proposed for the binding of alpha(1-2) linked mannotriose and tetraose to ConA. PMID- 1504038 TI - The contribution of halogen atoms to protein-ligand interactions. AB - The three-dimensional structure of para-fluoro-D-phenylalanine (PFF) in its complex with the zinc protease carboxypeptidase A (CPA) has been determined at 2.0 A resolution by X-ray crystallographic methods. The structure reveals that the para-fluorobenzyl side chain of the inhibitor is buried in the S'1 hydrophobic pocket of the enzyme. Intriguingly, this ligand molecule inhibits CPA better than its amino acid analogues D-phenylalanine (D-Phe) and D-tyrosine (D Tyr) by factors of 4 and 5, respectively. Moreover, the para-fluoro derivative is a better inhibitor than para-chloro- or para-bromo-D-phenylalanine by nearly a factor of 50. This result is consistent with binding enhancements realized in other protein complexes involving halogenated ligand molecules, regardless of whether the carbon-halogen group of the ligand makes specific polar interactions or non-specific hydrophobic interactions with its protein host. In the CPA-PFF complex, the fluorine atom of PFF does not make any direct polar contact with the enzyme, and the contact surface area of the protein-ligand interface is only slightly greater, although more hydrophobic, than that of D-Phe and D-Tyr. Therefore, we conclude that the slight binding enhancement measured for PFF relative to D-Phe and D-Tyr arises predominantly from increasing the hydrophobic character of the protein-ligand interface, and not solely from increasing the degree of protein-ligand contact. PMID- 1504039 TI - Chemical modification of arginyl residues in silk fibroin: 1. Reaction of 1,2 cyclohexanedione in borate buffer. AB - Chemical modifications of silk fibroin were attempted in order to add new properties and functions to silk fibroin. The arginyl residue in solubilized silk fibroin was chemically modified with the reaction of 1,2-cyclohexanedione in borate buffer. FT-i.r. and c.d. spectra of the silk fibroin before and after the modification indicated that the fraction of random coil conformation increased with the modification. The chemical stability of the modified silk fibroin membrane was investigated in vitro with phosphate buffer. The modified arginyl residue in the membrane was considerably regenerated with the treatment in phosphate buffer. PMID- 1504040 TI - Interaction of two fragments of cibacron blue F3GA having anthraquinone chromophores with basic polypeptides. AB - The interaction of two anthraquinone dyes, bromaminic acid 1-amino-4-bromo anthraquinone-2-sulphonic acid (BA) and 1-amino-4-(4'-aminophenylamino) anthraquinone-2,3'-disulphonic acid (ASSO), with poly-L-lysine (PLL), poly-L ornithine (PLO) and poly-L-arginine (PLA) has been studied. The flexibility of the side chain (chain length) and the geometry of the charge centre (tetrahedral/planar) of the polypeptide were found to affect the interaction. Further, both dyes induce ordered conformation (alpha or beta) for the three polypeptides, but the final conformation was found to depend on the polypeptide as well as the number of anionic sites on the ligand. While the bidentate ASSO polypeptide complexes acquire beta-conformation, the monodentate BA distinguished between the three substrates and induces beta-conformation only for PLO. PMID- 1504041 TI - Chemical modification of proteins under high pressure. Preparation of ferrocene attached bovine serum albumin and glucose oxidase. AB - High hydraulic pressure was used for denaturing proteins during chemical modifications. Bovine serum albumin and glucose oxidase were selected as the first targets of this unique technique and the ferrocene group was introduced into them, to obtain a macromolecular electron mediator and a self-electron mediating oxidase, respectively. The result was compared with those obtained under non-denaturing conditions and under urea-denatured conditions. As for the number of ferrocene group linked to the protein, the pressure denaturation is superior to chemical denaturants, where ferrocenecarboxyaldehyde was used as the modifier. In both proteins the ferrocene group seemed to be introduced mainly inside the molecules with the pressure method, as the native conformation of the protein was restored when the high pressure was removed. PMID- 1504042 TI - Studies on the function mechanism of a Formosan grey mullet protamine-mugiline beta M6: interaction of the M6 and M6 fragments with DNA. AB - The interaction of three peptide segments of one component of Formosan grey mullet protamine (mugiline beta M6), obtained by chemical and enzymatic cleavage, with DNA was studied by spectroscopic measurement, thermal denaturation and circular dichroism. The data obtained were then compared with those of whole M6 and other fish protamines such as salmine of salmon and clupeine of herring. M6-B I, which lacks C-terminal 11 amino acids in M6, showed significantly different properties. It showed remarkably high DNA aggregating ability which was due to a conformational change of DNA from B to A form. The conformational change of DNA induced by the binding of M6-B-I was reproduced by the carboxypeptidase B digestion of DNA-M6 complex. From these results, the arginine-rich, C-terminal domain of the M6 molecule was estimated to be essential for natural DNA binding. PMID- 1504043 TI - Single crystals of alpha-chitin. AB - Single crystals of alpha-chitin were grown by the addition of precipitants to dilute solutions of low molecular weight chitin fractions dissolved in aqueous LiSCN. At temperatures around 200 degrees C, bundles of thin needle-shaped crystals were obtained. Each of these needles was an alpha-chitin single crystal, characterized by a spot electron diffraction pattern which could be indexed along the hk0 reciprocal net corresponding to the Minke and Blackwell unit cell [a = 0.474 nm, b = 1.88 nm, c (fibre axis) = 1.032 nm, space group P2(1)2(1)2(1)]. In a crystal, the a* parameter was along the crystal axis and the b* perpendicular to it. PMID- 1504044 TI - Studies on chitosan: 4. Lysozymic hydrolysis of partially N-acetylated chitosans. AB - The lysozymic digestibility of partially N-acetylated chitosans was studied by measuring the reducing sugars produced and the molecular weights of their hydrolysates. Moderately N-deacetylated chitosans (MDC), obtained by N deacetylation of chitin under heterogeneous conditions, were about four times more digestible at an early stage than partially N-acetylated chitosans (PAC-H) with similar acetyl content, prepared by N-acetylation of highly N-deacetylated chitosans under homogeneous conditions. The molecular weights of the hydrolysates of MDC decreased rapidly but gradually reached a constant value in contrast to the behaviour of PAC-H. The Km was 0.14 mM for 30% N-acetylated MDC and 0.12 mM for 65% N-acetylated PAC-H although the degree of N-acetylation of the latter was twice as much as the former. These differences were due to the different distribution patterns of N-acetyl groups in two types of the chitosans. MDC with 20-30% acetyl content have the sequences of more than three N-acetyl-D glucosamine residues but PAC-H with about 30% acetyl content are random-type copolymers of N-acetyl-D-glucosamine and D-glucosamine units. PAC-H with more than 50% acetyl content have the sequences of more than three N-acetyl-D glucosamine residues. PMID- 1504045 TI - Conformation ability test of human, rabbit and bovine plasminogens and their specific interaction with streptokinase. AB - Human, rabbit and bovine plasminogens, having different sensitivity to streptokinase-activating action, differ, according to spectrophotometric titration, tryptophan fluorescence and circular dichroism spectroscopy, in the state of tyrosine and tryptophan residues, and in secondary and tertiary structures. Human plasminogen-streptokinase equimolar complex formation (according to gel chromatography) is accompanied by a differential ultraviolet spectrum. Difference spectroscopy is a convenient and adequate means of studying the formation of the said complexes. Streptokinase-human plasminogen complex formation is not hindered by partial substitution of water (20%) with ethanol or dimethylsulphoxide or by addition of 0.001 M sodium dodecylsulphate. The complex is not formed in 6 M urea, in solution, at pH less than 2.0 or approximately 12.0 13.0, or with bovine plasminogen. Circular dichroism and tryptophan fluorescence spectral pattern changes during streptokinase-plasminogen complex formation enable us to conclude that streptokinase secondary and tertiary structures undergo certain rearrangements in the framework of the complex, while tryptophan containing sites of the molecule are not drastically changed. The data obtained enable us to presuppose formation of streptokinase-rabbit plasminogen complexes which differ from human plasminogen complexes with streptokinase. PMID- 1504047 TI - GCI: a network server for interactive 3D graphics. AB - The Graphics Command Interpreter (GCI) is an independent server module that can be interfaced to any program that needs interactive three-dimensional (3D) graphics capabilities. The principal advantage of GCI is its simplicity. Only a limited set of powerful features have been implemented, including object management, global and local transformations, rotation, translation, clipping, scaling, viewport operations, window management, menu handling and picking. GCI and the master (client) program it serves run concurrently, communicating over a local or remote TCP/IP network. GCI sets up socket communication and provides a 3D graphics window and a terminal emulator for the master program. Communication between the two programs is via ASCII strings over standard I/O channels. The implied language for messages is very simple. GCI interprets messages from the master program and implements them as changes of graphical objects or as text messages to the user. GCI provides the user with facilities to manipulate the view of the displayed 3D objects interactively, independently of the master program, and to communicate mouse-controlled selection of menu items or 3D points as well as keyboard strings to the master program. The program is written in C and initially implemented using the Silicon Graphics GL graphics library. As the need to link special libraries to the master program is completely avoided, GCI can very easily be interfaced to existing programs written in any language and running on any operating system capable of TCP/IP communication. The program is freely available. PMID- 1504046 TI - Extracellular poly(hydroxyalkanoate) depolymerases and their inhibitor from Pseudomonas lemoignei. AB - Enzymatic degradation processes of microbial copolyesters, poly(3-hydroxybutyrate co-3-hydroxyvalerate): P(3HB-co-3HV) and poly(3-hydroxybutyrate-co-4 hydroxybutyrate): P(3HB-co-4HB), were studied by the weight loss (erosion) of copolyester films. These studies employed three extracellular depolymerases which degrade poly(3-hydroxybutyrate): P(3HB). Two enzymes were purified from the culture supernatant of Pseudomonas lemoignei and one from Alcaligenes faecalis T1. The rate of enzymatic degradation of microbial copolyester films with various compositions showed an almost similar tendency to three different P(3HB) depolymerases, and decreased in the following order: P(3HB-co-4HB) greater than P(3HB) greater than P(3HB-co-3HV). An inhibitory protein of P(3HB) depolymerases in the succinate culture medium of P. lemoignei was isolated and characterized. The molecular weight of P(3HB) depolymerase inhibitor was 35,000 as determined by polyacrylamide gel electrophoresis in the presence of sodium dodecyl sulphate. This inhibitor of a single polypeptide chain may reversibly bind the serine residues at the active site of P(3HB) depolymerase. This inhibitory protein was not induced in the culture medium when P. lemoignei was grown on P(3HB) as the sole carbon source. PMID- 1504048 TI - DNA and protein tetragrams: biological sequences as tetrahedral movements. AB - A graphical approach is introduced for representing information-containing sequences in biology. In particular, the procedure takes DNA or protein sequences containing n bases or amino acids, respectively, and computes n three-dimensional real vectors. When displayed on connected tetrahedra these characteristic patterns appear as DNA or amino acid tetragrams T(n). Experiments indicate that these tetragrams are sensitive to certain important patterns in the sequence of bases and allow the human observer to visually detect various properties of biological sequences. The system presented is special in its focus on the fast characterization of the progression of sequence data using a graphics supercomputer with several controlling parameters. PMID- 1504049 TI - VisiCoor: a simple program for visualization of proteins. AB - A well-drawn picture acts as an excellent metaphor for something real, and human vision provides instant, random access to any part of which the picture represents. It is in this sense that pictures can convey information more effectively than words alone. The power of the graphics work-stations available today makes visual presentation of scientific results a reality. A molecular graphics program for investigating protein structures, as well as several sample plots that show the power of the program, are presented. PMID- 1504050 TI - A crystallographic molecular lattice builder applied to model lipid bilayers. AB - It is often desirable for noncrystallographers to generate graphical models of three-dimensional crystal structures based on published coordinates of the atoms that make up the crystallographic unit cells. This type of visualization is particularly important for small-molecule crystals, such as lipid crystals, where one may be interested in investigating interactions between the individual molecules in addition to their conformations. BILAYER BUILDER is a program that generates a portion of the entire crystal structure from the coordinates of the molecules in a single unit cell. It gives users of small desktop computers, such as the Apple Macintosh, the capability to generate and examine model crystal structures with a molecular graphics display program. BILAYER BUILDER stores the crystal coordinates in a Brookhaven Protein Data Bank file format for possible use in a variety of applications on many different computers. Initially, it was written for use with lipid crystals and bilayers but may be used for building an assortment of molecular crystals. PMID- 1504051 TI - A graphics program for the analysis and display of molecular dynamics trajectories. AB - The program SCARECROW has been developed to help the molecular modeler to analyze and display the very big and complex data files produced by molecular dynamics programs. The molecular graphics program SCARECROW is written to support the display, animation, and extensive analysis of molecular dynamics trajectories. Using the macro language it is easy to make scripts for video animation and for the automated display and analysis of time series. Extensive coloring and atom selection commands are included to help the user to focus on relevant regions of the molecule. Time series can be produced and viewed on the screen or transferred to other programs. PMID- 1504052 TI - A phase II study of recombinant interleukin-2 with or without recombinant interferon-beta in non-Hodgkin's lymphoma. A study of the Cancer and Leukemia Group B. AB - Interleukin-2 (IL-2) and interferon-beta (IFN-beta) have demonstrated activity against lymphoid malignancies, presumably mediated by the augmentation of lymphokine-activated killer (LAK) cell and natural killer (NK) cell activity. There is in vitro and in vivo evidence to suggest that the combination of IL-2 and IFN-beta is synergistic. The Cancer and Leukemia Group B (CALGB) conducted a randomized phase II trial of IL-2 with or without IFN-beta in 49 patients with relapsed or refractory non-Hodgkin's lymphoma (NHL). Overall toxicity was severe, with 17 patients experiencing life-threatening toxicity. Three patients had treatment-related deaths. Responses were noted in seven patients (17%). There were no meaningful differences between treatment arms in toxicity profile, response rate, or modulation of in vivo NK and LAK activity. We conclude that IL 2 with or without IFN-beta is not effective therapy for NHL in the doses and schedule used in this study. PMID- 1504053 TI - Rapid cytokine release in cancer patients treated with interleukin-2. AB - Serum concentrations of interleukin-2 (IL-2), tumor necrosis factor-alpha (TNF alpha), interferon-gamma (IFN-gamma), interleukin-6 (IL-6), interleukin-1 (IL-1) and interferon-alpha (IFN-alpha) were determined by commercially available enzyme linked immunosorbent assay (ELISA) or radioimmunoassay (RIA) in cancer patients treated with recombinant IL-2 (rIL-2) either as 1-h infusion (3 or 5 x 10(6)/m2) or continuous intravenous infusion for 5 days (3 x 10(6)/m2/day). A significant increase of TNF-alpha and IL-6 serum levels was observed in each patient. One hour infusion of IL-2 induced a very rapid secretion of TNF-alpha, IL-6 and IFN gamma with considerably higher peak levels than during IL-2 continuous intravenous infusion. IFN-gamma was released into the blood of all patients receiving IL-2 1-h infusion, but only occasionally during or after IL-2 continuous intravenous infusion. Neither IFN-alpha nor IL-1 were detectable in the serum before, during, or following IL-2 treatment in all patients studied. The kinetics of IL-2 after 1-h infusion fitted to a two-compartment model, suggesting the synthesis of considerable amounts of endogenous IL-2. Following IL 2 1-h infusion, rising TNF-alpha serum levels preceded the increase of serum IFN gamma or IL-6. The serum peak levels of IFN-gamma and IL-6 decreased rapidly with a half-life of 0.29 to 2.5 h. The concentration time profiles of TNF following 1 h infusion of IL-2 demonstrated a considerably longer half-life than that of intravenously administered recombinant TNF as done in other studies.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1504054 TI - In vivo administration of recombinant macrophage colony-stimulating factor induces macrophage-mediated antibody-dependent cytotoxicity of tumor cells. AB - Macrophage colony-stimulating factor (M-CSF) has been previously shown to facilitate the in vitro survival and differentiation of mononuclear phagocytes. We assessed whether M-CSF administration in vivo could induce macrophages capable of killing tumor via an antibody-dependent mechanism. C57BL/6 mice were given intraperitoneal M-CSF, and peritoneal macrophages were assayed for their ability to kill fluorochrome-labeled R1.1 thymoma cells in vitro in the presence or absence of target-specific antibody. Two-color flow cytometry was used in measuring tumor ingestion by macrophages; macrophages from M-CSF-treated mice eliminated greater than 90% of R1.1 thymoma target within 24 hours, while macrophages from saline-treated controls were ineffective. R1.1 tumor elimination by macrophages depended on the presence of target-specific antibody. These are the first studies that demonstrate the in vivo induction, by M-CSF, of macrophages directly capable of ingesting antibody-conjugated tumor cells. PMID- 1504055 TI - Phase I study of recombinant human interleukin-2 for pediatric malignancies: feasibility of outpatient therapy. A Pediatric Oncology Group Study. AB - Published data indicate that when recombinant interleukin-2 (rIL-2) is administered to children as a 15-min i.v. bolus, doses of 18 x 10(6) IU/m2 are poorly tolerated, requiring intensive care unit (ICU) management of IL-2-induced hypotension. We administered rIL-2 as a 1- or 2-h i.v. infusion to 11 children with malignancies refractory to conventional therapy. IL-2 was given every Monday/Wednesday/Friday for 3 weeks. Four children received 12 x 10(6) IU/m2/dose, four received 18 x 10(6) IU/m2/dose, and three received 24 x 10(6) IU/m2/dose (1 Cetus Unit = 6 IU). Fever, chills, flushing, nausea, vomiting, transient weight gain, and oliguria were observed at all three dose levels (not dose-limiting toxicities). Cardiovascular toxicity was significantly reduced compared to the bolus regimen. Mild hypotension was observed at all three dose levels; however, there was no severe dose-limiting hypotension. Because of reduced cardiovascular toxicity, IL-2 was safely administered on an outpatient basis. This regimen induced marginal transient increases in natural killer cell activity and lymphokine-activated killer cell activity. No measurable clinical tumor response was observed in any of the 11 children. The maximum-tolerated dose has not been reached. This regimen allows for a considerable cost reduction (outpatient care instead of ICU care) and safety, making further clinical trials on the use of IL-2 in children more feasible. PMID- 1504056 TI - Bryostatin 1 activates T cells that have antitumor activity. AB - Several strategies have been used to stimulate the growth of tumor-specific T cells in place of tumor antigen. One approach is to use pharmacologic agents to activate the second messenger pathways of T-cell activation. In the present study, we examined the ability of the protein kinase C activator bryostatin 1 (B) plus the calcium ionophore ionomycin (I) to stimulate the growth of lymphocytes obtained from the axillary lymph nodes (DLN) draining a progressively growing intradermal plasmacytoma tumor. Draining lymph node cells were initially cultured with autologous tumor cells and 20 U/ml of interleukin-2 (IL-2) for 7 days. The lymphocytes were then incubated with various concentrations of bryostatin 1 plus 1 microM ionomycin and cultured for an additional 14 days in IL-2. DLN cells initially cultured with autologous tumor and then restimulated with 5 nM bryostatin 1 and 1 microM ionomycin exhibited marked in vitro proliferation and 15-fold expansion of cell numbers over 2 weeks. The cells expanded with B/I were predominantly CD8+ T cells and retained specific in vitro cytotoxicity against autologous tumor. When adoptively transferred to mice with established liver metastases, DLN cells restimulated with B/I-mediated specific tumor regression. PMID- 1504057 TI - Modulation of tumor-infiltrating lymphocytes derived from human renal cell carcinoma by interleukin-4. AB - Current methods of expanding tumor-infiltrating lymphocytes (TILs) from renal cell carcinoma bulk cultures result in a heterogeneous population of cells with low tumor-killing specificity. To improve the yield of cells with higher autologous and lower nonspecific cytotoxicity, interleukin-4 (IL-4) was added to high (1,000 U/ml)- and low (20 U/ml)-dose IL-2 and compared to cultures grown without IL-4 for proliferation, phenotype, and cytotoxicity against targets including autologous and allogeneic tumors. When compared to culture in IL-2 alone, the addition of IL-4 improved overall expansion in both high-dose (mean fold expansion of 2,061 vs. 1,087) and low-dose (mean fold expansion of 1,904 vs. 262) IL-2. Enhancement of TIL proliferation was dependent on the timing of IL-4 addition to the culture; augmented growth occurred only when IL-4 was added with or following activation by IL-2. The phenotype consisted primarily of CD3+/CD4+ lymphocytes with a reciprocal reduction in CD56+/CD16+ cells. Finally, there was a significant reduction in nonspecific cytotoxicity against K-562, M-14, and allogeneic tumor targets, but no significant change against autologous tumor. We conclude that IL-4 has an important regulatory effect on the expansion of renal cell carcinoma TILs in IL-2 by the promoting growth of CD3+/CD4+ lymphocytes and inhibiting the growth and nonspecific cytotoxicity associated with LAK-like CD16+/CD56+ cells. These findings may be beneficial in extracting more potent effector cells from bulk TIL culture for use in clinical trials. PMID- 1504058 TI - Activation of human monocytes by interleukin-2 and various cytokines. AB - We previously reported that human macrophages cultured with IL-2 for a long period (lymphokine-activated macrophages, LAMs) showed high tumoricidal activity against human and murine leukemic cell lines through a different mechanism from lymphokine-activated killer (LAK) cells. In this report, we investigated the effects of various cytokines on the tumoricidal activity of IL-2-induced LAMs against HeLa cells. CSF-1 and IL-1 were found to enhance the tumoricidal activity of LAM in a dose-dependent manner, whereas IFN-gamma and TNF had inhibitory effects. CSF-1 in combination with a low dose of IL-2 synergistically induced LAMs with highly tumoricidal activity. We also found that monocytes from some donors that did not respond to IL-2 were differentiated to tumoricidal macrophages by treatment with a combination of CSF-1 and IL-2. Furthermore, IL-2 induced LAMs were found to produce cytotoxic factors in the culture medium when they were cocultured with tumor cells, and the cytotoxic activity in the culture supernatant of LAMs was also increased by the incubation of LAMs with CSF-1. The cytotoxicity of the supernatants from macrophages with different tumoricidal activity correlated with their cell-mediated cytotoxicity. It is suggested from these results that the cytotoxicity of LAMs is regulated by CSF-1, IL-1, IFN gamma, and TNF, and that the production of cytotoxic molecules is involved in cell-mediated killing by LAMs. PMID- 1504059 TI - European Collection for Biomedical Research. PMID- 1504060 TI - Antidepressant activity of S-adenosyl-L-methionine in mice and rats. AB - S-Adenosyl-L-methionine (SAM), main methyl donor, was tested in mice and rats in several models which are predictive of possible antidepressant activity. In the forced swimming test in rats the effect of SAM was compared with that of the tricyclic antidepressant amitriptyline. SAM decreased dose-dependently immobility time in the forced swimming test in mice and rats, these effects being antagonized by haloperidol and prazosin (the latter only in rats). Locomotor or exploratory activity in mice and rats was not increased by SAM. D-Amphetamine induced locomotor hyper-activity in rats was increased by repeated (14 days, twice daily) treatment with SAM. Behavioural stimulation induced by D-amphetamine or L-dopa (given with benserazide) in mice was not changed by a single dose of SAM. The drug reduced hypothermia induced by apomorphine in mice. Hypothermia induced by reserpine or clonidine in mice was not antagonized. SAM increased the amplitude of the acoustic startle reflex. The above results indicate that the psychopharmacological profile of SAM resembles that of antidepressants in only some tests. The mechanism by which SAM produces its antidepressant effect needs further investigation. PMID- 1504061 TI - Amitriptyline attenuates the febrile response to a pyrogen in rabbits. AB - We investigated the effect of a tricyclic antidepressant (TCA) agent on fever in rabbits. In the first series of experiments, the TCA agent amitriptyline hydrochloride (AMI) was administered intraperitoneally (i.p.) at a dose of 1 mg/kg or 10 mg/kg daily for three weeks. The rabbit's response to intravenous (i.v.) injection of 0.1 micrograms/kg of the lipopolysaccharide (LPS) of Salmonella typhosa was tested on a weekly basis. In the second series of experiments, rabbits were given simultaneous i.v. injections of either 1 mg/kg or 10 mg/kg of AMI together with 0.1 microgram/kg of LPS. After two weeks of chronic i.p. administration of 10 mg/kg AMI, and for the remainder of the experimental period, the rabbit's response to the LPS was significantly attenuated when compared to control animals. When AMI was administered simultaneously with the LPS, a significant dose-dependent antipyresis was observed from 50 minutes after injection, compared to the response of control animals. AMI had no effect on the body temperature of afebrile animals. PMID- 1504062 TI - Melatonin levels are decreased in rheumatoid arthritis. AB - The hormone, melatonin, is a product of the pineal gland. This methoxy-indole, also known as N-acetyl-5-methoxy-tryptamine, is structurally related to indomethacin, a derivative of methylated indole. The fact that indomethacin has been used successfully in patients suffering from certain chronic inflammatory conditions (such as rheumatoid- and osteoarthritis) gives rise to the question as to whether melatonin also possesses anti-inflammatory virtues. This hypothesis has been tested by determining melatonin concentration levels by means of a radioimmunoassay in patients with rheumatoid arthritis. The daytime melatonin levels of untreated patients were significantly lower (mean concentration = 5.76 pg/ml) than the normal value (mean concentration = 15-33 pg/ml). The second part of this study showed that the administration of indomethacin (100 mg/day) to normal healthy subjects led to a 14.7 pg/ml decrease in plasma melatonin levels. This may indicate that melatonin and indomethacin act synergistically. PMID- 1504063 TI - Peripheral-type mitochondrial binding sites for benzodiazepines in GH3 pituitary cells. AB - Benzodiazepines (BZs) interact with two classes of high affinity binding sites, equilibrium dissociation constants in the nanomolar range, a neuronal or central type and a non-neuronal or peripheral-type. The peripheral-type binding site has been shown to be present on the outer mitochondrial membrane and appears to be involved in regulation of cholesterol transport in steroid hormone-producing endocrine cells. In rat pituitary GH3 cells, BZs bind to receptors for thyrotropin-releasing hormone (TRH) and via interaction at a different site block Ca2+ influx through voltage-sensitive channels. These, however, are low affinity interactions occurring at micromolar BZ concentrations. Here, using [3H]Ro 5 4864, we report that GH3 cells also have high affinity peripheral-type BZ binding sites. Apparent equilibrium dissociation constants of 7.8 +/- 1.7 nM and 9.3 +/- 4.5 nM for [3H]Ro 5-4864 were measured with intact cells and isolated mitochondria, respectively. As predicted from studies of these sites in other cells, the order of potencies of BZs to displace [3H]Ro 5-4864 was Ro 5-4864 greater than diazepam (DZP) much greater than clonazepam (CIZP); chlordiazepoxide (CDE) did not affect binding. Nifedipine, a dihydropyridine antagonist of Ca2+ channels that has been shown to displace BZs from peripheral-type sites in other cells, was shown to be a competitive inhibitor of [3H]Ro 5-4864 binding with a half-effective concentration in the micromolar range. Ro 5-4864, however, had no effect on Ca2+ influx or efflux in mitochondria isolated from GH3 cells. Hence, GH3 cells exhibit mitochondrial, peripheral-type BZ binding sites but the role of these putative receptors in these neuroendocrine cells, which do not produce steroid hormones, is unclear. PMID- 1504064 TI - Pentazocine reduces cholinergic responses in the guinea-pig extrahepatic biliary tract by a non-opiate mechanism. AB - The mechanical responses of the guinea-pig gallbladder and common bile duct to pentazocine were measured in vitro. At concentrations of 1 microM or higher, pentazocine reduced the responses of the gallbladder and common bile duct to electrical stimulation and to carbachol. This antagonism was not blocked by naloxone and appears to be due to an atropine-like action of pentazocine. At concentrations of 5 microM or higher pentazocine induced gallbladder contraction which was naloxone-insensitive. Both effects were not affected by tetrodotoxin and appear to be due to direct action on the muscle. The antimuscarinic activity of pentazocine should be taken into consideration when this opioid is administered experimentally or clinically. PMID- 1504065 TI - The concentration dependence of the depolarization of yeast by monovalent cations. AB - Monovalent cations decrease the initial rate of uptake of the membrane potential probe 2-(dimethylaminostyryl)-1-ethyl-pyridinium (DMP) into metabolizing cells, showing that the cells are depolarized. A steep decrease in this rate was found even at low cation concentrations, reaching 62%, 42%, 58%, 40% and 40% at high concentrations of K+, Rb+, Cs+, Na+ and Li+, respectively. The corresponding concentrations at which half-maximum decrease was found were 0.22, 0.36, 1.2, 17 and 17 mM. These values are of the same order of magnitude as the half-saturation concentrations for monovalent cation uptake by the yeast. PMID- 1504066 TI - Lithium fluxes in Paramecium and their relationship to chemoresponse. AB - Paramecia respond to environmental stimuli by altering swimming behavior to disperse from or accumulate in the vicinity of the stimulus. We have found, using the T-maze assay, that treatment of paramecia with LiCl in a time- and concentration-dependent manner modifies the normal response to folate, acetate, and lactate from attraction to no response or even repulsion. Responses to NH4Cl were unaffected and to cAMP were variably affected by LiCl. Cells incubated in the presence of K+, or both Na+ and K+, but not Na+ alone reliably recovered attraction to folate. Treatment of cells with 4 mM LiCl for 1 h dramatically slowed swimming speed from about 1 mm/s in NaCl or KCl (control) to 0.18 mm/s in LiCl. Li-treated cells subsequently incubated in 4 mM NaCl, KCl or sequentially in KCl and NaCl for a total of 20 min increased their swimming speed to 0.35, 0.45 and 0.67 mm/s, respectively. Paramecia readily took up Li+ in Na(+)- and K(+)-free media reaching intracellular concentrations of 5-10 mM in 10 mM extracellular Li+. Efflux of intracellular Li+ was stimulated 35% by extracellular 10 mM NaCl and 185% by 10 mM KCl over 10 mM choline chloride. Incubation of cells in 10 mM LiCl for 1 h inhibited the rate of Ca2+ efflux by 44% compared to cells in 10 mM NaCl. This may relate to the mechanism by which Li+ perturbs chemoresponse. A mutant with defects in Ca homeostasis responds normally to NH4Cl, but not to any of the stimuli that are affected by LiCl. PMID- 1504067 TI - Transbilayer incorporation of 1-pyrenebutyltrimethylammonium by blood platelets and its application for analyzing changes in physico-chemical properties of the membrane lipid bilayer induced by platelet activation. AB - The binding of cationic butyltrimethylammonium derivative of pyrene to bovine platelets was initially rapid and then increased gradually, unlike the bindings of other anionic and neutral derivatives of pyrene tested. The rate of increase in binding of the cationic probe depended on temperature and was due to its incorporation into the cytoplasmic side of the platelet membranes, as shown quantitatively by monitoring decrease in its extractability with albumin. The penetration into the inner membrane compartment did not reach equilibrium even after 4 h at 37 degrees C. Slow penetration of a fluorescent probe such as this is useful in studies on the physico-chemical properties of the outer layer and cytoplasmic side of the platelet membranes and their changes. Initial rapid binding of the cationic probe to platelets, representing the binding of the probe to the outer layer of the plasma membrane, was increased by ionomycin-induced platelet activation. Fluorescence spectra in the presence of a relatively high concentration of the cationic probe showed increase of the excimer of the cationic probe accompanied with the incorporation of the probe to the cytoplasmic side. On ionomycin-induced activation, the excimer-to-monomer intensity ratio of the probe in the cytoplasmic side of the platelet membranes decreased, possibly due to decrease in fluidity of the lipid layer near the probe or change in distribution of the probe. PMID- 1504068 TI - Involvement of histidine residues and sulfhydryl groups in the function of the biotin transport carrier of rabbit intestinal brush-border membrane. AB - Possible involvement of histidine residues and sulfhydryl groups in the function of the intestinal brush-border membrane (BBM) transporter of biotin was investigated. This was done by examining the effects of pretreatment of BBM vesicle (BBMV) isolated from rabbit intestine with the histidine-specific reagent diethyl pyrocarbonate (DEPC) and the sulfhydryl group-specific reagents p chloromercuribenzenesulfonic acid (p-CMBS) and 7-chloro-4-nitrobenz-2-oxa-1,3 diazole (NBD-Cl) on carrier-mediated biotin transport. Pretreatment of BBMV with DEPC caused significant inhibition in the initial rate of biotin transport without affecting the substrate uptake at equilibrium. Addition of biotin plus Na+ to vesicle suspensions prior to treatment with DEPC provided significant protection to biotin transport. Treatment of DEPC-pretreated vesicles with the reducing agents dithiothreitol and 2,3-dimercaptopropanol failed to reverse the inhibitory effect of DEPC on biotin transport. The inhibitory effect of DEPC was found to be mediated through a marked decrease in the number of the functional biotin transport carriers with no change in their affinity, as indicated by the severe inhibition in the Vmax but not the apparent Km of the biotin transport process, respectively. Pretreatment of BBMV with p-CMBS and NBD-Cl also caused significant inhibition in the initial rate of biotin transport without affecting the substrate uptake at equilibrium. Addition of biotin plus Na+ to vesicle suspensions prior to treatment with p-CMBS (or NBD-Cl) failed to protect biotin transport from inhibition. On the other hand, treatment of vesicles pretreated with p-CMBS (or NBD-Cl) with the reducing agents dithiothreitol and mercaptoethanol caused significant reversal in the inhibition of biotin transport. The inhibitory effects of p-CMBS (and NBD-Cl) on biotin transport was also found to be mediated through inhibition in the Vmax, but not the apparent Km, of biotin transport process. These results indicate the involvement of histidine residues and sulfhydryl groups in the normal function of the biotin transport system of rabbit intestinal BBM. Furthermore, the results also suggest that the histidine residues are probably located at (or near) the substrate binding site while the sulfhydryl groups are located at a site other than the substrate binding region. PMID- 1504069 TI - Merocyanine 540 as a probe to monitor the molecular packing of phosphatidylcholine: a monolayer epifluorescence microscopy and spectroscopy study. AB - The characteristics of the fluorescent dye, merocyanine 540 (MC-540), incorporated in monolayers of 1,2-dipalmitoyl-phosphatidylcholine (DPPC), and 1 palmitoyl-2-oleoylphosphatidylcholine (POPC) were studied in different states of molecular packing. Conditions for phase separation in these monolayers were defined by their pressure/area (pi-A) isotherms. Within the liquid expanded (LE) and the liquid condensed (LC) coexisting phases of DPPC monolayers, low light level epifluorescence microscopy revealed 'dark' discoid domains embedded in a 'bright' matrix. Under the same conditions, and at temperatures as low as 12 degrees C, the pi-A isotherms of POPC demonstrate the existence of a single phase, and no fluorescent domains were observed. Fluorescence spectra of MC-540 labelled monolayers, recorded in different structural states, reveal three distinct emission peaks: a 572 nm peak, present for monolayer packing conditions at low surface pressures; a 585 nm peak, similar to that obtained from dye molecules in fluid phase lipid bilayers, and observed here within the respective area/molecule ranges of 54-62 A2 and 62-69 A2 for monolayers of DPPC and POPC with diminishing intensity at increasing surface pressure; and finally, a peak at 560 nm, which predominates in densely packed POPC monolayers. Our results are interpreted on the basis of dye partitioning between monolayer and subphase, and different orientations of the dye with respect to the monolayer in various structural states. The usefulness of MC-540 to differentiate lipid packing in cell membranes is discussed. PMID- 1504070 TI - A role for the transient increase of cytoplasmic free calcium in cell rescue after photodynamic treatment. AB - Chinese hamster ovary (CHO) cells and T24 human bladder transitional carcinoma cells were treated with the photosensitizers aluminum phthalocyanine (AlPc) and hematoporphyrin derivative (HPD), respectively. Exposure of both sensitized cell lines to red light caused an immediate increase of cytoplasmic free calcium, [Ca2+]i, reaching a peak within 5-15 min after exposure and then returning to basal level (approximately 200 nM). The level of the peak [Ca2+]i depended on the light fluence, reaching a maximum of 800-1000 nM at light doses that kill about 90% of the cells. Loading the cells with the intracellular calcium chelators quin2 or BAPTA prior to light exposure enhanced cell killing. This indicates that increased [Ca2+]i after photodynamic therapy (PDT) contributed to survivability of the treated cells by triggering a cellular rescue response. The results of experiments with calcium-free buffer and calcium chelators indicate that both in CHO cells treated with AlPc and with HPD-PDT of T24 cells extracellular Ca2+ influx is mainly responsible for elevated [Ca2+]i. PDT is unique in triggering a cell rescue process via elevated [Ca2+]i. Other cytotoxic agents, e.g., H2O2, produce sustained increase of [Ca2+]i that is involved in the pathological processes leading to cell death. PMID- 1504071 TI - The permeability and the effect of acyl-chain length for phospholipid bilayers containing cholesterol: theory and experiment. AB - The model of Cruzeiro-Hansson et al. (Biochim. Biophys. Acta (1989) 979, 166 1176) for lipid-cholesterol bilayers at low cholesterol concentrations is used to predict the thermodynamic properties and the passive ion permeability of lipid bilayers as a function of acyl-chain length and cholesterol concentration. Numerical simulations based on the Monte Carlo method are used to determine the equilibrium state of the system near the main gel-fluid phase transition. The permeability is calculated using an ansatz which relates the passive permeability to the amount of interfaces formed in the bilayer when cholesterol is present. The model predicts at low cholesterol contents an increase in the membrane permeability in the transition region both for increasing cholesterol concentration and for decreasing chain length at a given value of the reduced temperature. This is in contrast to the case of lipid bilayers containing high cholesterol concentrations where the cholesterol strongly suppresses the permeability. Experimental results for the Na+ permeability of C15PC and DPPC (C16PC) bilayers containing cholesterol are presented which confirm the theoretical predictions at low cholesterol concentrations. PMID- 1504072 TI - Amphotericin B-phospholipid interactions responsible for reduced mammalian cell toxicity. AB - When interacting with phospholipid in an aqueous environment, amphotericin B forms unusual structures of markedly reduced toxicity (Janoff et al. (1988) Proc. Natl. Acad. Sci. USA 85, 6122-6126). These structures, which appear ribbon-like by freeze-fracture electron microscopy (EM), are found exclusively at amphotericin B to lipid mole ratios of 1:3 to 1:1. At lower mole ratios they occur in combination with liposomes. Circular dichroism (CD) spectra revealed two distinct modes of lipid-amphotericin B interaction, one for liposomes and one for the ribbon-like structures. In isolated liposomes, amphotericin B which comprised 3-4 mole percent of the bulk lipid was monomeric and exhibited a hemolytic activity comparable to amphotericin B suspended in deoxycholate. Above 3-4 mole percent amphotericin B, ribbon-like structures emerged and CD spectra indicated drug-lipid complexation. Minimal inhibitory concentrations for Candida albicans of liposomal and complexed amphotericin B were comparable and could be attributed to amphotericin a release as a result of lipid breakdown within the ribbon-like material by a heat labile extracellular yeast product (lipase). Negative stain EM of the ribbon-like structures indicated that the ribbon-like appearance seen by freeze-fracture EM arises as a consequence of the cross-fracturing of what are aggregated, collapsed single lamellar, presumably interdigitated, membranes. Studies examining complexation of amphotericin B with either DMPC or DMPG demonstrated that headgroup interactions played little role in the formation of the ribbon-like structures. With these results we propose that ribbon-like structures result from phase separation of amphotericin B-phospholipid complexes within the phospholipid matrix such that amphotericin B release, and thus acute toxicity, is curtailed. Formation of amphotericin B-lipid structures such as those described here indicates a possible new role for lipid as a stabilizing matrix for drug delivery of lipophilic substances, specifically where a highly ordered packing arrangement between lipid and compound can be achieved. PMID- 1504073 TI - A second phenazine methosulphate-linked formate dehydrogenase isoenzyme in Escherichia coli. AB - A biochemical and immunological study has revealed a new formate dehydrogenase isoenzyme in Escherichia coli. The enzyme is an isoenzyme of the respiratory formate dehydrogenase (FDH-N) which forms part of the formate to nitrate respiratory pathway found in the organisms when it is grown anaerobically in the presence of nitrate. The new enzyme, termed FDH-Z, cross reacts with antibodies raised to FDH-N and possesses a similar polypeptide composition to FDH-N. FDH-Z catalyses the phenazine methosulphate-linked formate dehydrogenase activity present in the aerobically-grown bacterium. FDH-Z and FDH-N exhibit distinct regulation. Like formate dehydrogenase N, formate dehydrogenase Z is a membrane bound molybdoenzyme. With nitrate reductase it can catalyse electron transfer between formate and nitrate. Quinones are required for the physiological electron transfer to nitrate. It seems likely that like FDH-N, FDH-Z functions physiologically as a formate: quinone oxidoreductase. PMID- 1504074 TI - Induction of a Ca(2+)-activated K+ channel in human erythrocytes by mechanical stress. AB - Mechanical deformation of normal ATP-replete human erythrocytes increased their permeability to Ca2+ sufficiently to turn on the Ca(2+)-activated K+ channel (the Gardos channel). When Ca2+ is absent, mechanical deformation of normal erythrocytes induces an equivalent increase the permeability of both Na+ and K+, In the presence of 0.1 to 1 mM Ca2+, a further increase in the K+ efflux rate was seen. There was no increase in Na+ flux above that induced by deformation itself. The involvement of the Ca(2+)-activated H channel was verified by showing the specific inhibitors of the channel, quinine and charybdotoxin, prevent the Ca(2+) induced increase in K+ efflux. These results are consistent with a model of sickle cell dehydration proposed by Bookchin et al. ((1987) Prog. Clin. Biol. Res. 240, 193-200). The estimated rate of Ca2+ entry under these conditions (37 degrees C, 1000 dyne/cm2, and laminar shear) was about 1 mmol/loc per h. PMID- 1504075 TI - Temperature-dependent effects of cholesterol on sodium transport through lipid membranes by an ionizable mobile carrier. AB - Temperature-jump relaxation experiments on Na+ transport by (221)C10-cryptand were carried out in order to study the influence of cholesterol and its temperature-dependence on ion transport through thin lipid membranes. The experiments were performed on large, negatively charged unilamellar vesicles (LUV) prepared from mixtures of dioleoylphosphatidylcholine, phosphatidic acid and cholesterol (mole fractions 0-0.43), at various temperatures and carrier concentrations. The initial rates of Na+ transport and the apparent rate constants of its translocation by (221)C10 increased with the carrier concentration and the temperature. The incorporation of cholesterol into the membranes significantly reduced the carrier concentration- and temperature dependence of these two parameters. The apparent energy required to activate the transport decreased significantly with increasing carrier concentrations at any given cholesterol molar fraction, and increased significantly with the cholesterol molar fraction at any given carrier concentration. Our interpretation of the action of cholesterol on this transport system is based on the assumption that the binding cavity of cryptands is likely to be located towards the aqueous side of the dipole layer. The results are discussed in terms of the structural, physico-chemical and electrical characteristics of carriers and complexes, and of the interactions occurring between an ionizable mobile carrier and the membrane. PMID- 1504076 TI - Freeze-fracture analysis of the effects of intermediates of the phosphatidylinositol cycle on fusion of rough endoplasmic reticulum membranes. AB - While searching for the identity of the effector of the putative GTP-binding protein involved in fusion of rough endoplasmic reticulum (RER) cell-free incubation conditions were found permitting fusion in a GTP-independent manner. Membrane fusion was obtained using medium required to study synthesis of phosphatidylinositol (PI). We now report on the effects of various co-factors and intermediates of the PI cycle on the interaction of rough microsomes. By freeze fracture, fusion of rough microsomes was defined as the appearance of fracture planes of membrane larger than those of unincubated membrane. Cytosine triphosphate (CTP, 3 mM) in the presence of 2 mM MnCl2 was most effective in stimulating fusion. Guanosine triphosphate (GTP) at the same concentration, could substitute for CTP to stimulate fusion, ATP, ITP, UTP and guanosine 5'-[gamma thio]triphosphate (GTP gamma S) could not. When combined together in the same medium CTP potentiated the effect of GTP. Arachidonic acid (20 micrograms/ml) also stimulated fusion in the presence of MnCl2. This led to the appearance of large fracture-planes of membrane with a heterogeneous distribution of intramembranous particles. Other saturated fatty acids at the same concentration did not stimulate fusion. Phosphatidylinositol (PI, 50 micrograms) and 2 mM MnCl2 had a similar effect as arachidonic acid and MnCl2 in stimulating fusion. The PI effect was largely augmented in the presence of CTP. Our results are consistent with the concept that metabolism of phospholipids may modulate GTP-dependent fusion of RER membranes. PMID- 1504077 TI - The relaxation effect as observed on lipid suspensions of low polydispersity. AB - Lipid suspensions with a low polydispersity (delta = 0.15 +/- 0.05, as given by photon correlation spectroscopy (PCS)) were used to elucidate the origin of the disagreement between the experimental zeta potential values (zeta sm), obtained from the electrophoretic mobilities through the Smoluchowski equation, and double layer theory prediction (zeta potential) at low salt concentrations. The values of zeta sm, measured for cardiolipin and phosphatidylserine suspensions in monovalent electrolytes, were compared with the correspondent theoretical values of the zeta potentials correlated for the relaxation effect; the correction was made according to the S.S. Dukhin theory of electrophoresis. It was found, that this correction eliminates the disagreement for cardiolipin in NaCl entirely; it partly solves the problem for cardiolipin in KCl but fails to improve the situation for phosphatidylserine in NaCl. PMID- 1504078 TI - Triggered release of hydrophilic agents from plasmalogen liposomes using visible light or acid. AB - Triggered release from liposomes composed of semi-synthetic 1-alk-1'-enyl-2-acyl sn-glycero-3-phosphocholine (plasmalogen) lipids has been demonstrated using either aerobic visible illumination or low pH to induce leakage. The photodynamic release system consists of three functional components: (1) small (less than 1000 A) unilamellar plasmalogen vesicles (SUVs) containing encapsulated glucose, (2) oxygen and (3) zinc phthalocyanine (ZnPc) incorporated within the hydrophobic region of the SUV membrane. Irradiation (lambda greater than 640 nm) at 37 degrees C of air-saturated 1-alk-1'-enyl-2-palmitoyl-sn-glycero-3-phosphocholine (PlasPPC)/1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) (8:1, mol/mol) liposomes at physiologically relevant temperatures results in glucose release rates that are twice those of the corresponding dark control. Photolysis of argon saturated PlasPPC/DPPC liposomes or of identical vesicles lacking either ZnPc or the plasmalogen vinyl ether bond exhibit glucose release curves which are indistinguishable from the dark control. Irradiation under identical conditions, but in the presence of 100 mM sodium azide, also results in no increased rate of glucose release above that of the dark control. TLC analysis indicates that oxidized lipid species are produced only in air-saturated, irradiated plasmalogen liposomes. The acid lability of the plasmalogen vinyl ether linkage has also been used to trigger release of entrapped calcein. At pH 4.2, the release rate at 37 degrees C is increased 4-fold over rates observed at pH 8. TLC analysis indicates formation of a lysoplasmalogen product. Taken together, these results indicate that both photodynamic and acid triggering can be used to increase plasmalogen liposome permeability and suggest that these liposomes are potentially useful for drug delivery applications. PMID- 1504079 TI - Effect of oligomers of ethylene glycol on thermotropic phase transition of dipalmitoylphosphatidylcholine multilamellar vesicles. AB - The effect of oligomers of ethylene glycol (EG) on thermotropic phase transitions of dipalmitoylglycerophosphatidylcholine multilamellar vesicles (DPPC-MLV) were investigated. Diethylene glycol (di-EG) had a biphasic effect on transition temperature, reducing pre-transition temperature (Tp) at low concentrations but increasing main transition temperature (Tm) and extinguishing pre-transition at high concentration. Results of the X-ray diffraction method and the excimer method indicated that di-EG induced interdigitated gel phase (L beta 1 phase) in the DPPC membranes at high concentration. Phase diagram of temperature-di-EG concentration for DPPC-MLV was determined by use of X-ray diffraction and differential scanning calorimetry, which was similar to that of temperature-EG concentration. The minimum concentration of di-EG where L beta 1 phase was induced was 42%(w/v), which was larger than that of EG (30%(w/v)). On the other hand, in the presence of triethylene glycol (tri-EG), Tm and Tp increased with an increased in tri-EG concentration, as well as poly(ethylene glycol). These differences, between the effects of di-EG and those of tri-EG, might be due to the differences of their sizes. PMID- 1504080 TI - Presence of small GTP-binding proteins in the peroxisomal membrane. AB - Highly purified peroxisomal membranes stripped from their peripheral membrane proteins and only minimally contaminated with other membranes, contained three GTP-binding proteins of 29, 27 and 25 kDa, respectively. Bound radioactive GTP was displaced by unlabelled GTP, GTP analogs and GDP but not by GMP or other nucleotides. GTP binding was markedly decreased by trypsin treatment of intact purified peroxisomes; it increased 2-3-fold after pretreatment of the animals with a peroxisome proliferator. We conclude that the peroxisomal membrane contains small GTP-binding proteins that are exposed to the cytosol and that are firmly anchored in the membrane. We speculate that these proteins are involved in peroxisome multiplication by fission or budding during peroxisome biogenesis and proliferation. PMID- 1504081 TI - Subcellular distribution of carbonic anhydrase in the enterocyte of the rabbit ileum and the Caco-2 cell. Evidence for the presence of two isozymes bound to brush-border membranes. AB - The activity of CA has been determined in the membranes of enterocytes from rabbit ileum and of Caco-2 cells. No CA activity was detected in the BLM, but the activity in the BBM (43 and 7 WAU/mg protein for rabbit and Caco-2, respectively) was doubled by the addition of Triton. These two types of activity could be distinguished in rabbit ileum by their different IC50 in the presence of acetazolamide (10(-5) and 5 x 10(-7) M) and their different sensitivities to heat. They were not modified by inhibitors of cytoplasmic isozymes and seem to correspond to two forms of CA, one situated in the extracellular leaflet of the BBM and the other one in the intracellular leaflet. PMID- 1504082 TI - Protein flux across the membrane of single secretion granules. AB - We have applied, for the first time to our knowledge, X-ray microscopy to measure the mass of protein contained in single sub-cellular membrane-bound structures and to make high resolution, time-resolved observations on them. Using this method we have been able to follow the flux of protein out of secretion (zymogen) granules isolated from the acinar cells of the exocrine pancreas. The results provide direct visual and quantitative confirmation of the hypothesis that the membrane enclosing this object is permeable to its various contained proteins, although the mechanism remains unknown. PMID- 1504083 TI - Effect of lipidic factors on membrane cholesterol topology--mode of binding of theta-toxin to cholesterol in liposomes. AB - We have previously suggested the existence of two distinct states for cholesterol in cell membranes as revealed by high- and low-affinity binding sites for theta toxin of Clostridium perfringens. In liposomes, phospholipid and cholesterol compositions, but not membrane protein composition, have been shown to be major determinants for the topology of membrane cholesterol. The effects of lipidic factors on cholesterol topology were investigated in detail by analyzing toxin binding to large unilamellar liposomes composed of cholesterol and phospholipids (neutral phospholipids/phosphatidylglycerol = 82:18, mol/mol). The numbers of high- and low-affinity toxin-binding sites depend strictly on the cholesterol mole percentage in liposomes. High-affinity toxin-binding sites appear only in liposomes with high cholesterol contents. Liposomes whose cholesterol/phospholipid ratio is 0.4 or less have no high-affinity sites regardless of their phospholipid compositions, while low-affinity sites appear in liposomes with lower cholesterol contents. The threshold values for the cholesterol mole percentage above which high-affinity toxin-binding sites appear were examined. The values decrease in accordance with the increase in the mole fraction of 18-carbon hydrocarbon chains among the total 14-18 carbon-hydrocarbon chains of the liposomal phospholipids. Furthermore, both the partial replacement of phosphatidylcholine with phosphatidylethanolamine and the digestion of phospholipids with phospholipase C also affect the threshold values. Thus the cholesterol mole percentage, in combination with phospholipid chain length and other factors, determines the topology of membrane cholesterol providing distinctively different affinity sites for theta-toxin. PMID- 1504084 TI - Tellurite-induced damage of the erythrocyte membrane. Manifestations and mechanisms. AB - Chemical and biophysical mechanisms underlying the thiol-dependent lytic action of tellurite (and selenite) on human erythrocytes were investigated using native and GSH-depleted cells. Exposure of GSH-depleted cells to tellurite alone produces oxidative cross-linking of membrane thiols paralleled by a moderate membrane leakiness comparable in its extent to that induced by other SH-oxidizing agents (diamide, periodate). Exposure to tellurite in presence of endogenous or exogenous GSH produces marked leakiness which stems from the formation of aqueous leaks permeant to ions and nonelectrolytes and sensitive to inhibition by phloretin. Apparent pore radii, derived from exclusion limits for polar non electrolytes, range from 0.3 to at least 1.3 nm. Leak size increases with increasing exposure time and concentration of the modifier. Leak formation is paralleled by membrane rigidification based on the cross-linking of spectrin. Thiol-dependent leak formation by tellurite in GSH-depleted cells can be sustained not only by exogenous GSH but also by other thiols. Progress of leak formation by tellurite/thiol can not be reliably quenched by procedures such as removal of tellurite from the medium, inhibition of anion transport via band-3 protein, washing of the cells or low temperature. The reaction can, however, be terminated, even in the presence of tellurite, by addition of N-ethylmaleimide, presumably due to the blockage of thiols or thiol-analogous tellurium compounds. N-ethylmaleimide even brings about a partial reversal of leakiness, suggesting the contribution of a reversible and an irreversible component of tellurite damage. Membrane perturbation by tellurite/thiol involves the formation of a membrane permeant tellurium species, possibly HTe-, which is likely to induce progressive damage of membrane proteins by a redox shuttle going along with a formation of elemental tellurium and its reduction by thiols. PMID- 1504085 TI - Denaturation of glucose-6-phosphate dehydrogenase from Leuconostoc mesenteroides by guanidine hydrochloride; identification of inactive, partially unfolded, dimeric intermediates. AB - The denaturation of the dimeric enzyme glucose-6-phosphate dehydrogenase from Leuconostoc mesenteroides by guanidine hydrochloride has been studied using enzymatic activity, intrinsic fluorescence, circular dichroism, and light scattering measurements. Equilibrium experiments at 25 degrees C revealed that between 0.9 and 1.2 M denaturant the enzyme underwent a conformational change, exposing tryptophan residues to solvent, with some loss of secondary structure and a complete loss of enzymatic activity but without dimer dissociation to subunits. This inactive, partially unfolded, dimeric intermediate was susceptible to slow aggregation, perhaps due to exposure of 'sticky' hydrophobic stretches of the polypeptide chain. A second equilibrium transition, reflecting extensive unfolding and dimer dissociation, occurred only at denaturant concentrations above 1.4 M. Kinetics experiments demonstrated that in the denaturant concentration range of 1.7-1.9 M the fluorescence change occurred in two distinct steps. The first step involved a large, very rapid drop in fluorescence whose rate was strongly dependent on the denaturant concentration. This was followed by a small, relatively slow rise in the emission intensity, the rate of which was independent of denaturant concentration. Enzymatic activity was lost with a denaturant-concentration-dependent rate, which was approx. 3-times slower than the rate of the first step in fluorescence change. A denaturation mechanism incorporating several unfolding intermediates and which accounts for all the above results is presented and discussed. While the fully unfolded enzyme regained up to 55% of its original activity upon dilution of denaturant to a concentration that would be expected to support native enzyme, denaturation intermediates were able to reactivate only minimally and in fact were found to aggregate and precipitate out of solution. PMID- 1504086 TI - Structural analysis of the interaction between the side-chain of substrates and the active site of lanosterol 14 alpha-demethylase (P-450(14)DM) of yeast. AB - The role of the side-chain of lanosterol in the enzyme-substrate interaction of yeast P-450(14)DM (lanosterol 14 alpha-demethylase) was analyzed with lanosterol derivatives having functional groups on the side-chain. Purified P-450(14)DM from Saccharomyces cerevisiae catalyzed 14 alpha-demethylation of 26-hydroxylanosterol and 25-hydroxy-24,25-dihydrolanosterol with a lower activity than lanosterol and 24,25-dihydrolanosterol. This enzyme demethylated the (Z)-24-ethylidene-24,25 dihydrolanosterol with a low rate, but did not metabolize the E-isomer. The apparent Km of 26-hydroxylanosterol was 10.8 microM, which was higher than that of lanosterol, but lower than that of 24,25-dihydrolanosterol. On the other hand, competition experiments suggested that the affinity of 25-hydroxy-24,25 dihydrolanosterol and (Z)-24-ethylidene-24,25-dihydrolanosterol for P-450(14)DM was significantly lower than that of 24,25-dihydrolanosterol. Integration of the present results with the preceding ones (Aoyama, Y., Yoshida, Y., Sonoda, Y. and Sato, Y. (1991) Biochim. Biophys. Acta, 1081, 262-266 and Aoyama, Y. and Yoshida, Y. (1991) Biochem. Biophys. Res. Commun., 178, 1064-1071) suggests that yeast P 450(14)DM recognizes two parts of the side-chain, the structure around C-24 and the terminal fork consisting of C-25, C-26 and C-27. PMID- 1504087 TI - Localization and characterization of hemoglobin-degrading aspartic proteinases from the malarial parasite Plasmodium falciparum. AB - Three hemoglobin-degrading proteinases were partially purified from food vacuoles isolated from trophozoite-stage forms of the malarial parasite Plasmodium falciparum. Two of the proteinases (M1 and M2) were solubilized by repeated sonication. The remaining proteinase (M3) was solubilized by treatment of the particulate fraction with taurocholic acid, suggesting that proteinase M3 is a membrane-bound proteinase whereas proteinases M1 and M2 are weakly associated with parasite membrane. The location of these proteinases suggests that they may participate in the digestion of host cytosolic protein. After partial purification, but not before, proteinases M1, M2 and M3 are highly sensitive to pepstatin, supporting their designation as aspartic proteinases. These aspartic proteinases show broad specificity for protein substrates. Native hemoglobin, acid denatured hemoglobin and oxidatively damaged hemoglobin are comparable substrates. Hemoglobin within the food vacuole was shown to be primarily native hemoglobin. Chemical modification studies indicate that these three aspartic proteinases have similar properties. The peptide maps from degradation of hemoglobin, however, suggest that aspartic proteinases M1, M2 and M3 are distinct proteinases. PMID- 1504088 TI - NADPH activates a decarboxylation reaction catalysed by lamb liver 6 phosphogluconate dehydrogenase. AB - NADP-dependent lamb liver 6-phosphogluconate dehydrogenase catalyses the oxidative decarboxylation of 2-deoxy-6-phosphogluconate, an analogue of the natural substrate. The first products of the reaction are NADPH and 3-keto-2 deoxy-6-phosphogluconate. The NADPH, released from the enzyme, binds to the coenzyme site of the same or the other subunit, activating the decarboxylation reaction in which has not a redox role, since it can be substituted by an analogue devoid of enzymatic redox power. These findings are compared to those obtained with other NADP-dependent decarboxylating dehydrogenases. PMID- 1504089 TI - A heat-stable serine proteinase from the extreme thermophilic archaebacterium Sulfolobus solfataricus. AB - A proteinase was purified to electrophoretic homogeneity from crude extracts of the thermoacidophilic archaebacterium Sulfolobus solfataricus. Molecular mass values assessed by SDS-PAGE and gel filtration were 54 and 118 kDa, respectively, which points to a dimeric structure of the molecule. An isoelectric point of 5.6 was also determined. The enzyme behaved as a chymotrypsin-like serine proteinase, as shown by the inhibitory effects exerted by phenylmethanesulfonyl fluoride, 3,4 dichloroisocoumarin, tosylphenylalaninechloromethyl ketone and chymostatin. Consistently with the inhibition pattern, the enzyme cleaved chromogenic substrates at the carboxyl side of aromatic or bulky aliphatic amino acids; however, it effectively attacked only a small number of such substrates, thus, displaying a specificity much narrower than and clearly different from that of chymotrypsin. This was confirmed by its inability to digest a set of natural substrate proteins, as well as insulin chains A and B; only after alkylation casein was degraded to some extent. Proteinase activity was significantly stimulated by Mn2+ which acted as a mixed-type nonessential activator. The enzyme also displayed a broad pH optimum in the range 6.5-8.0. Furthermore, it was completely stable up to 90 degrees C; above this temperature it underwent first order thermal inactivation with half-lives ranging from 342 min (92 degrees C) to 7 min (101 degrees C). At 50 degrees C it could withstand 6 M urea and, to some extent, different organic solvents; however, at 95 degrees C it was extensively inactivated by all of these compounds. None of the chemical physical properties of the enzyme, including amino-acid analysis, provided evidence of a possible relation to other well-known microbial serine proteinases. PMID- 1504090 TI - Conversion of non-functional to functional iron following reconstitution of hemerythrin. AB - A recent report from this laboratory (Zhang, J.-H., Kurtz, D.M., Jr., Xia, Y.-M. and Debrunner, P.G. (1991) Biochemistry 30, 583-589) described a procedure for reconstitution of a functional di-iron site in the octameric, non-heme iron O2 carrying protein, hemerythrin by addition of ferrous salts to apoprotein, followed by slow dilution of the denaturant. Although the resulting protein contained its full complement of iron, i.e., 2 Fe per subunit, about 30% of the iron was found to remain ferrous under ambient O2, i.e., this iron was incapable of forming an O2 adduct. In this report a method is described for obtaining essentially fully functional hemerythrin by passage of the freshly reconstituted protein through an [oxy/30% non-functional----met----deoxy----oxy redox cycle. UV/vis absorption and 57Fe Mossbauer spectroscopies show that little or no non functional iron remains in the reconstituted oxyhemerythrin after the redox cycle. Quantitations of protein and diiron sites show that, during the first step of the redox cycle, the non-functional iron is converted to a form that is spectroscopically indistinguishable from that of native methemerythrin. Far-UV circular dichroism shows that the secondary structure of this reconstituted methemerythrin is essentially identical to that of native protein. Non-denaturing polyacrylamide gel electrophoresis shows that the size and charge of the native and reconstituted proteins before and after redox cycling are essentially identical. These results indicate that the non-functional iron is converted to a functional form by the redox cycling, and that the key step in this conversion is the [oxy/30% non-functional]----met transformation. PMID- 1504091 TI - Effect of NaCl addition on nanosecond O2 escaping reaction of myoglobin: evidences for the transition of myoglobin dynamic structure at 20 degrees C. AB - We studied the nanosecond (ns) geminate O2 escape reaction from the protein interior of myoglobin (Mb) to the solvent phase in the temperature range of 5-40 degrees C containing 0-0.1 M NaCl. In the flash photolysis experiments, we found that both the rate constant, kout, and its Arrhenius plot changed upon the variation of the NaCl concentration. In particular, it was noteworthy that the Arrhenius plot of kout dramatically changed in its slope, keeping the break at 20 degrees C, upon the addition of NaCl, indicating that the thermodynamic parameters such as an enthalpy of activation (delta H not equal to) and an entropy of activation (delta S not equal to) are different between above and below 20 degrees C, and that they are further altered upon the NaCl addition to the sample solution. From these results, we suggested that the Mb dynamic structure in the ns geminate O2 escape reaction is sensitively regulated by the interaction of the protein surface and the salt. The present study also showed that an inconsistency of the Arrhenius plot of kout between Chatfield et al. ((1990) J. Am. Chem. Soc. 112, 4680-4687) and us ((1990) J. Biol. Chem. 265, 18823-18828) is probably due to the difference in the solution condition. PMID- 1504092 TI - Hydrophobic interaction of lysozyme and alpha-lactalbumin from equine milk whey. AB - From fluorescence measurements on mixtures of bis-ANS and equine lysozyme and from Ca(2+)-dependent hydrophobic interaction chromatography of equine lysozyme, it is demonstrated that Ca2+ binding induces a conformational change upon which hydrophobic regions in the protein become less accessible. Bis-ANS fluorescence titrations in the absence of Ca2+ and in 2 mM Ca2+ are also performed with equine alpha-lactalbumin variants B and C. These variants differ by an amino-acid exchange Asp----Ile at residue 95. The fluorescence titration curves indicate that the accessibility of the probe to the Ca2+ conformers is clearly influenced by the mutation. The Ca(2+)-dependent exclusion of a hydrophobic domain is used in a new and simplified method for preparing lysozyme and alpha-lactalbumins simultaneously from equine milk whey. PMID- 1504093 TI - Adenosine deaminase from Saccharomyces cerevisiae: kinetics and interaction with transition and ground state inhibitors. AB - Several adenosine analogs, such as coformycin, 2'-deoxycoformycin and erythro-9 (3-nonyl-p-aminobenzyl)adenine (EHNA), which are strong inhibitors of mammalian adenosine deaminase, are much weaker inhibitors of the Saccharomyces cerevisiae enzyme. The specificity of the yeast enzyme is more restricted than that of mammalian adenosine deaminase, particularly towards the ribose moiety and around position 6 and 1 of the substrate. The sulphydryl group appears to be more masked in the yeast than in the mammalian enzyme. The kinetic effects of pH with adenosine substrate and with the inhibitor purine riboside are reported. The findings on specificity and pH kinetic effects can be interpreted in a model involving proton transfer from the -SH group of the enzyme to the N-1 atom of the substrate. PMID- 1504094 TI - Promotion of beta-structure by interaction of diabetes associated polypeptide (amylin) with phosphatidylcholine. AB - The interaction of the diabetes associated polypeptide (amylin) with dimyristoylphosphatidylcholine (DMPC) was assessed by measurements of turbidity (absorbance at 400 nm) and secondary structure by CD spectroscopy. In trifluoroethanol, human amylin adopts a highly alpha-helical conformation while the rat peptide is less structured. In water, the rat peptide is largely disordered and the human peptide exhibits a combination of alpha- and beta structures. Mixtures of DMPC and the rat peptide have no effect on either the turbidity of the DMPC or the CD spectrum of the peptide. By contrast, mixtures of the human peptide with DMPC form relatively clear mixtures similar to those observed with amphipathic alpha-helical peptides, but the structure adopted, based on the CD spectrum, is largely beta. These data demonstrate that fundamental differences in the structures adopted by amylins from human and rat species exist in mixtures with DMPC and suggest that these differences may be related to the formation of amyloid fibrils in the human amylin peptide which are not observed in the rat peptide. PMID- 1504095 TI - Limited proteolysis of chicken gizzard 5'-nucleotidase. AB - Chicken gizzard 5'-nucleotidase represents an ectoenzyme which is linked to the plasma membrane via a phosphatidylinositol glycan. We have characterized the possible domain-like organization of 5'-nucleotidase by limited proteolysis. A hydrophobic proteolytic fragment carrying the intact C-terminus, as well as two major hydrophilic products, were identified. We developed procedures for specific radiolabelling of the active center of 5'-nucleotidase. This allowed us to locate the catalytic site within hydrophilic fragments obtained after limited proteolysis. We demonstrate that removal of N-linked carbohydrate chains increases the sensitivity of 5'-nucleotidase to proteolytic attack, indicating that sugar moieties protect against proteolysis. 5'-Nucleotidase represents a binding protein for components of the extracellular matrix. The interaction between 5'-nucleotidase and the laminin/nidogen complex unmasked proteolytic cleavage sites in the C-terminal portion of the enzyme. This resulted in the specific production of a hydrophilic form of 5'-nucleotidase. In summary, we have further characterized chicken gizzard 5'-nucleotidase: (1) the protein is organized into two domain-like structures, (2) the N-terminal domain harbors the active center; (3) N-linked carbohydrates protect the protein against proteolytic degradation; (4) interaction with components of the extracellular matrix alters the conformation of 5'-nucleotidase. PMID- 1504096 TI - Structure and metabolism of multiple heparan sulphate proteoglycans synthesized by the isolated rat glomerulus. AB - Metabolism of biosynthetically [35S]sulphate-labelled heparan sulphate proteoglycan (HSPG) was studied in the isolated glomerulus. Chromatography and electrophoresis resolved HS into 5 components, designated HS1a, HS1b, and HS2 to HS4 in order of increasing Kd. Both HS1a (250 kDa) and HS1b (130 kDa) are present in the glomerular basement membrane and have glycosaminoglycan chains of 25-45 kDa. Chemical analysis of glycosaminoglycan chains indicated a similar content of 50% N-sulphation and 30% 6-O-sulphation on the hexosamine residues of all HSs, with the remaining 20% of sulphate likely at the 2-O-position of uronic acid residues. By pulse-chase analysis, the basement-membrane fraction was found to have a half-life of residency in the glomerulus of 37 h. Both HS1a and HS1b are mainly released intact into the medium and are not further broken down in that compartment. In contrast, HS2 is almost completely released into the medium immediately after synthesis and is not normally recovered from the tissue. It is a 90-kDa HSPG with a hydrophobic core protein and glycosaminoglycan chains similar in size to those of HS1. In addition to these larger PGs, HS3 and HS4 represent glycosaminoglycan chains with little or no core protein. HS1a, HS1b and HS2 were iodinated and deglycosylated. Each has a 30-kDa core protein in addition to 18 kDa of chondroitinase ABC- and nitrous-acid-resistant O-linked carbohydrate. This suggests the possibility of a single core protein with variable glycosylation and destination. HS1a has 5-6 glycosaminoglycan chains, HS1b 2-3 and HS2 1-2. We propose that basement-membrane HSPG (HS1a and HS1b) and a related, underglycosylated secreted HSPG (HS2) are the major HSPGs synthesized by the isolated glomerulus. Other molecular species may represent discrete steps in the turnover of basement-membrane HSPG. PMID- 1504097 TI - Ammonium chloride-induced acidification in renal TALH SVE.1 cells monitored by 31P-NMR. AB - The aim of this study was to investigate the effect of NH4+ on the intracellular pH in TALH SVE.1 cells derived from the medullary thick ascending limb of Henle's loop (TALH) of rabbit kidney. These cells are specialized to perform NH4+ transport in vivo. Intracellular pH was monitored by 31P-NMR. The steady state intracellular pH (pHi) under standard conditions was 7.24 +/- 0.04 (n = 46). Exposure to NH4Cl resulted in an initial intracellular acidification of the TALH SVE.1 cells, followed by a recovery to the initial steady-state pHi value. The NH4(+)-induced acidification followed saturation kinetics up to 20 mM NH4Cl (delta pHmax = 0.2 pHunits). Half-maximal acidification was observed at 0.6 mmol/l. The intracellular acidification due to NH4Cl exposure was completely inhibited by 0.1 mM of the diuretic bumetanide, an inhibitor of the Na+/K+/2Cl- cotransporter. The effect of bumetanide was dose-dependent and a Ki value of 8.10(-7) M was calculated. NH4+ influx via K+ channels or the (Na+ + K+)ATPase could not be detected. pHi recovery to the initial value was caused mainly by amiloride-sensitive Na+/H+ exchange and to a lesser extent by an amiloride insensitive system, which was not studied in detail. In the presence of bumetanide, pulses of high concentrations of NH4Cl induced small intracellular alkalinizations. From these experiments, an intrinsic buffer capacity (beta i) in TALH SVE.1 cells of 26 +/- 3 mM x pH-1 (pHi = 7.65) was determined. It could also be shown that the TALH SVE.1 cells exhibit maximal 'functional buffer capability' between pHout 6.9 and 7.3. Within these limits the cells can maintain their intracellular pH at a constant level, even though the extracellular pH changes. These data strongly suggest that the Na+/K+/2Cl- cotransporter is the main site of NH4+ entry into rabbit thick ascending limb cells in culture. A high intracellular buffer capacity and potent acid extrusion mechanism cooperate in counteracting the intracellular acidification caused by NH4+ influx into the cell. PMID- 1504098 TI - Abnormal accumulation and toxicity of polyamines in a difluoromethylornithine resistant HTC cell variant. AB - Mammalian cells possess an inducible, active polyamine transport system that is stringently regulated by feedback controls. This study provides evidence that DH23b cells, which were initially selected from the rat hepatoma HTC line for overproduction of ornithine decarboxylase, demonstrate an abnormality in the regulation of polyamine transport. Exposure of these cells to micromolar levels of spermidine or spermine resulted in inhibition of protein synthesis and eventual cell lysis. These effects were not due to by-products of polyamine oxidation by serum oxidases as neither inhibition of protein synthesis nor cell lysis was mitigated by aminoguanidine, reduced glutathione, dithiothreitol, or catalase. Although the polyamine transport system in the DH23b cells has the same Km and Vmax as that in the parental HTC line, the variant cells accumulated abnormally high levels of both spermidine (8-times normal) and spermine (4-times normal). In the HTC line, however, transport of both polyamines as well as putrescine was feedback inhibited within approx. 3 h, while in the variant cells uptake was not diminished by 12 h and terminated only with cell lysis. The DH23b cells appear to lack the normal mechanism responsible for feedback control of active polyamine incorporation. This defect provided the opportunity to manipulate intracellular levels of spermidine from 30 to approx. 800% of normal, allowing the demonstration that cellular protein synthesis is as sensitive to spermidine levels as previous in-vitro studies had suggested. PMID- 1504099 TI - Guanine nucleotides stimulate carboxyl methylation of kidney cytosolic proteins. AB - We studied the effect of guanine nucleotides on the carboxyl methylation catalyzed by class II protein carboxylmethyltransferases (PCMT). Addition of guanosine 5'-O-(gamma-thio)triphosphate (GTP gamma S) promoted a time- and concentration-dependent enhancement of protein methylation in the cytosolic fraction isolated from kidney cortex. GTP gamma S affected the kinetics of the methylation reaction, as reflected by alterations of both apparent Km and Vmax of the methyltransferase. This effect was specific for guanine nucleotides and was completely abolished by addition of S-adenosyl-L-homocysteine, a well-known inhibitor of methyltransferase-catalyzed reactions. No GTP gamma S stimulation of methylation was found in cytosolic extracts from any of the other tissues studied, including brain, testis, spleen, and liver, nor in brush-border membranes isolated from the kidney cortex. The methylated proteins were highly sensitive to moderately alkaline conditions, suggesting that the methyl esters were formed on L-isoaspartyl residues and thus methylated by a class II PCMT. These results suggest that class-II-associated protein methylation activity from the soluble fraction of the kidney can be regulated by guanine nucleotides. PMID- 1504100 TI - Measurement of intracellular Ca2+ in young and old human erythrocytes using 19F NMR spectroscopy. AB - Elevated cell calcium has been implicated in functional changes with human erythrocyte aging. However, until recently it has been difficult to measure free ionic intracellular calcium in red cells. We have made use of a fluorinated calcium chelator probe (5,5'-difluoroBAPTA) and fluorine nuclear magnetic resonance (19F-NMR) techniques to measure changes of intracellular Ca2+ concentrations ([Ca2+]i) with cell aging. We have demonstrated in these studies that human erythrocyte [Ca2+]i is significantly elevated as a function of in-vivo aging. Young cells, the least dense fraction of density-separated erythrocytes, contained an average of 62 (+/- 4) nM Ca2+ (+/- S.E.), whereas the oldest, most dense cell fraction contained 221 nM Ca2+ (+/- 25). Mechanisms by which intracellular [Ca2+] increases with in-vivo aging are currently under investigation. PMID- 1504101 TI - Glucocorticoid stimulation of amnion cell prostaglandin synthesis: suppression by protein kinase C inhibitors and independence of phorbol ester-sensitive protein kinase C. AB - Glucocorticoids stimulate the prostaglandin E2 production of confluent amnion cell cultures, but have no stimulatory effect on the PGE2 output of freshly isolated human amnion cells. Since protein phosphorylation may modify the responsiveness of target cells to steroids, and activators of protein kinase C (PKC), as well as corticosteroids, promote amnion cell PGE2 output by stimulating the synthesis of prostaglandin endoperoxide H synthase (PGHS), we investigated the possibility that PKC is involved in the glucocorticoid-induction of PGE2 synthesis in cultured amnion cells. The dexamethasone-induced PGE2 output of arachidonate-stimulated cells was blocked by the protein kinase inhibitors staurosporine, K-252a, H7, HA1004, and sphinganine, in a manner consistent with their effect on PKC. However, dexamethasone increased the PGE2 production of cultures treated with maximally effective concentrations of the PKC-activator compound TPA. Moreover, dexamethasone stimulated PGE2 synthesis in cultures which were desensitized to TPA-stimulation by prolonged phorbol ester treatment. Concentration-dependence studies showed that staurosporine completely (greater than 95%) blocked glucocorticoid-provoked PGE2 synthesis at concentrations which did not inhibit TPA-stimulated prostaglandin output, and that K-252a inhibited the effect of TPA by more than 95% at concentrations which decreased the effect of dexamethasone only moderately (approximately 40%). Dibutyryl cyclic AMP had no influence on the basal- or dexamethasone-stimulated PGE2 production, and on the staurosporine inhibition of the steroid effect. These results show that glucocorticoids and phorbol esters control amnion PGE2 production by separate regulatory mechanisms. It is suggested that the response of human amnion cells to glucocorticoids is modulated by protein kinase(s) other than phorbol ester sensitive PKC and cyclic AMP-dependent protein kinase. PMID- 1504102 TI - Sphingolipid metabolism and signal transduction: inhibition of in vitro phospholipase activity by sphingosine. AB - Sphingosine inhibits protein kinase C activity in vitro and has been used to implicate this enzyme in signal transduction and cell function. We report that sphingosine directly inhibits phospholipases A2 and D. Sphingosine inhibits Ca(2+)-dependent phospholipases A2 from Naja naja, porcine pancreas, Crotalus adamanteus, human disc and neutrophil in a dose-dependent manner with IC50 values ranging from 5-40 microM using [1-14C]oleate-labelled autoclaved E. coli (20 microM) as substrate. Inhibition is comparable using the same concentrations (20 microM) of [1-14C]oleate-labelled C. albicans or E. coli, or aqueous dispersions of 1-acyl-2-[1-14C]linoleoylglycerophosphoethanolamine or -choline. Sphinganine and stearylamine are as inhibitory as sphingosine; monoolein is less inhibitory (IC50 = 70 microM), while octylamine, N-acetylsphingosine, sphingomyelin and ceramide have no effect. Inhibition is relieved by increasing concentrations of substrate phospholipid. The molar ratio of sphingosine to phospholipid required for 50% inhibition ranges from 0.5 to 1.0 with 2-100 microM E. coli phospholipid. In contrast, sphingosine has a biphasic effect on the hydrolysis of E. coli by S. chromofuscus phospholipase D; concentrations less than or equal to 25 microM stimulate activity while concentrations greater than 25 microM are inhibitory. Addition of Triton X-100 eliminates both the stimulatory and inhibitory effects of sphingosine on phospholipase D activity. PMID- 1504103 TI - Exo-protein kinase release from intact cultured aortic endothelial cells. AB - Extracellular protein kinase activity is demonstrated in intact cultured porcine aortic endothelial cells and is characterised. When cells were incubated with [gamma-32P]ATP (1 microM) a major cell surface protein, corresponding to 115 kDa, and at least four serum proteins (19, 21, 55 and 126 kDa) became phosphorylated. Protein kinase activity is released by intact endothelial cells, which is not due to cell damage, as judged by various cell viability parameters (e.g., release of marker enzymes, trypan blue exclusion). The activity of the protein kinase released amounted to 170 fmol/min per mg endothelial cell protein with phosvitin as substrate, which represents 9% of the total cellular phosvitin protein kinase activity. Repetitive incubation of endothelial cells substantially decreased phosvitin-kinase release. Exo-protein kinase is not influenced by cAMP and cGMP but is effectively inhibited by heparin (EC50, 0.3 microgram/ml). The findings clearly demonstrate: (1) exo-protein kinase is released by intact porcine aortic endothelial cells; (2) substrates of this enzyme are endothelial surface proteins and serum proteins. PMID- 1504104 TI - Poly(ADPR)polymerase expression and activity during proliferation and differentiation of rat astrocyte and neuronal cultures. AB - Poly(ADPR)polymerase (poly(ADPR)P) mRNA and enzymatic activity levels were investigated in primary cultures of rat astrocytes and neurons in the absence or presence of basic fibroblast growth factor (bFGF) and nerve growth factor (NGF), respectively. In cultured rat astrocytes, a biphasic increase in poly(ADPR)P mRNA, associated with enhanced nuclear poly(ADPR)P enzymatic activity, were observed. The first rise in poly(ADPR)P mRNA and enzymatic activity is at the beginning of cell proliferation and the second with the occurrence of cell differentiation. In the presence of bFGF (5 ng/ml) the mRNA peaks and the differentiation-associated poly(ADPR)P enzymatic activity undergoes a 2-fold increase. In neuronal cultures an initial high level of poly(ADPR)P mRNA is followed by a decrease while differentiation is progressively achieved. A limited increase of poly(ADPR)P activity is observed during this phase. In the presence of NGF (50 ng/ml), similar poly(ADPR)P mRNA expression and enzymatic activity patterns are observed. The results suggest that poly(ADPR)P is involved at the onset of nerve-cell proliferation and differentiation. PMID- 1504105 TI - Cell-free phosphorylation of the murine small heat-shock protein hsp25 by an endogenous kinase from Ehrlich ascites tumor cells. AB - The small heat-shock protein hsp25 of the Ehrlich ascites tumor exists in one non phosphorylated (hsp25/1) and two phosphorylated (hsp25/2, hsp25/3) isoforms. In stationary phase tumor cells, a protein kinase activity was detected which phosphorylates hsp25/1, resulting in the formation of several phosphorylated hsp25 isoforms, including those occurring naturally in the tumor. Cell-free phosphorylation of hsp25 required Mg2+ and ATP and was independent of Ca2+, phosphatidylserine, cAMP and cGMP. Polymyxin B inhibited, specifically, hsp25 phosphorylation, whereas trifluoperazine, staurosporine and the protein inhibitor of protein kinase A had no effect. In its properties, the hsp25 phosphorylating kinase differs from other common kinases such as protein kinases A and C, calcium/calmodulin-dependent kinases, and the ribosomal protein S6 kinase. PMID- 1504106 TI - cAMP-dependent protein kinases in the rat testis: regulatory and catalytic subunit associations. AB - Based upon recent reports that the rat testis exhibits mRNAs for cAMP-dependent protein kinase (A-kinase) regulatory (R) subunits RI alpha, RI beta, RII alpha, and RII beta, this study was designed to identify R proteins present in extracts of germ cell-rich testis from adult and Sertoli cell-enriched, germ cell-poor testis from 14-15-day-old rats. Following separation by DEAE-cellulose, R subunits were identified by Mr: (a) upon labeling with 8-N3[32P]cAMP and 32P in an RII phosphorylation reaction and; (b) by Western blot analysis using R specific antibodies on one- and two-dimensional gel electrophoresis. Elution of R subunits as catalytic (C) subunit-free dimers or in association with C subunits to form holoenzyme was determined by their sedimentation characteristics on sucrose gradient centrifugation in conjunction with their cAMP-stimulated activation characteristics on Eadie-Scatchard analysis. Soluble extracts of testes, from both adult and 14-15 day-old rats, showed the presence of a prominent type I holoenzyme containing RI alpha subunits (47 kDa, peak 1), a minor type II holoenzyme, containing RII beta subunits (52 kDa, peak 2), and a second, more abundant, type II holoenzyme peak containing predominantly RII alpha and, to a lesser extent RII beta subunits (peak 3). The 53 kDa RI beta protein predicted by mRNA studies was only tentatively identified by Western blot analysis. Testes extracts of 14-15-day-old, but not adult, rats exhibited high levels of C subunit-free RI alpha, a result not predicted by mRNA studies. This latter result may be attributable to direct RI alpha regulation or to indirect RII beta regulation at a time during testis development prior to germ cell maturation. PMID- 1504107 TI - Amylin inhibits insulin-stimulated glucose uptake in C2C12 muscle cell line through a cholera-toxin-sensitive mechanism. AB - Rat amylin inhibits insulin-stimulated glucose uptake with an IC50 of 12.1 +/- 4.1 pM in C2C12 myotubes. The maximal inhibition is 64 +/- 5.4% observed at a 100 pM dose of the peptide. Consistently, presence of 100 pM amylin shifted the dose response curve of insulin to the right, increasing the ED50 from 0.71 to 16 nM. No effect of amylin is observed on basal glucose uptake in these cells. Cholera toxin treatment of the cells did not affect the insulin-stimulated glucose uptake, while the inhibitory effect is completely lost in toxin-treated cells. These findings strongly suggest that rat amylin is active at a physiological concentration and the amylin inhibition of glucose uptake is mediated through a cholera-toxin-sensitive mechanism. PMID- 1504108 TI - Hypofrontality on topographic EEG in schizophrenia. Correlations with neuropsychological and psychopathological parameters. AB - Topographic EEG was performed in 17 DSM-III-R schizophrenic patients and in 15 sex- and age-matched healthy controls. Eleven patients were first-onset (neuroleptic naive) schizophrenics. EEG band power was compared with psychopathology, neuropsychology and neurological soft signs. The EEG was recorded at 14 topographic locations monopolarly and movements of the eye and of the lid were monitored by two bipolar electro-oculogram (EOG) derivations, one vertical and one horizontal. A multivariate correction of EOG artefacts was performed based on regression analysis with respect to EOG channels. Schizophrenic patients showed higher mean and median power in most bands. These differences were marked in the delta band, in the fast alpha and beta bands, in particular at left frontal sites. Delta power at F7 was by far the best separating variable between schizophrenics and controls in a discriminant analysis. Significant positive correlations were found between the Brief Psychiatric Rating Scale scores "Anxiety-depression" and "Activation" and power in the fast bands and negative ones between "Anergia" and the beta bands. Positive significant correlations emerged between the total score in the Negative Symptoms Rating Scale and the amount of delta power, predominantly over the temporal region. Impairment in the Luria-Nebraska neuropsychological scores "Rhythm" and "Memory" correlated highly significantly with EEG band power. No correlations were found between neurological soft signs and EEG band power. Our results are in line with the hypothesis of a hypofrontality in schizophrenia. It is unlikely that these findings are an artefact of prior psychiatric treatment, as they were also observed in first-onset, neuroleptic naive schizophrenics.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1504109 TI - Smooth pursuit eye movements and neuropsychological tests in schizophrenic patients: possible involvement of attentional components. AB - The relationships among different components of frontal lobe dysfunction and voluntary attention were studied. Drug-free schizophrenic patients and matched normal controls were recruited and assessed for smooth pursuit eye movements, voluntary saccadic eye movements and by means of neuropsychological tests (Toluse Pieron test and Wisconsin Card Sorting Test). No clear-cut relationship was found between eye movement performance and neuropsychological impairment. PMID- 1504110 TI - Anxiogenic properties of yohimbine. I. Behavioral, physiological and biochemical measures. AB - The anxiogenic effects of yohimbine, a specific alpha-2-receptor antagonist were examined by administering 20 mg yohimbine orally to 8 panic patients on placebo treatment, 7 panic patients on alprazolam treatment and 12 controls using a double-blind randomized design, instructions that minimized the expectancy of experiencing a panic attack and two additional structured situations. Yohimbine induced more pronounced increases in anxiety and panicky ratings, norepinephrine secretion, maximum heart rate and high heart rate variability and decreases in skin temperature in panic patients compared with controls. However, possibly owing to an instructional set and experimental design that distracted patients from unpleasant bodily sensations no panic attacks were observed. PMID- 1504111 TI - Anxiogenic properties of yohimbine. II. Influence of experimental set and setting. AB - To study the pharmacological induction of stress along with psychological stress and their possible interaction, 20 mg yohimbine and placebo orally were administered to 8 panic patients on placebo treatment, 7 panic patients on alprazolam treatment and 12 controls in a double-blind crossover design. Two structured situations which can be considered as 'neutral' stressors were included: a mental arithmetic task and a continuous performance task. Mental arithmetic induced robust increases in ratings of panicky, anxiety, nervousness, heart rate and electrodermal activity, while the continuous performance task induced increases exclusively in skin conductance reaction. Patients responded to these tasks less than controls with regard to subjective ratings and electrodermal activity. Yohimbine did not potentiate the response to the tasks in the patients. In controls, heart rate during the mental arithmetic task, but not during rest, was increased after yohimbine. In contrast to other yohimbine challenge studies no panic attacks were observed. It is hypothesized that the experimental design together with an instructional set that reduces expectancy factors and the inclusion of structured and time-limited tasks in a challenge paradigm is able to reduce the anxiogenic effects of yohimbine. PMID- 1504112 TI - The deleterious effect of ocular artefacts on the quantitative EEG, and a remedy. AB - The effect of ocular artefacts on spectral EEG parameters is assessed statistically. These artefacts are caused by movements of the eyeball and/or of the lid. Further, methods for correcting ocular artefacts are presented and evaluated. This methodological study is based on data from an investigation comparing the EEG of schizophrenic patients (n = 17) with healthy controls (n = 15). Ocular artefacts are monitored by the bipolar vertical and the bipolar horizontal electro-oculogram (EOG). It is shown that the influence of ocular artefacts on the measured electrical activity in the frontal region is larger than the cerebral potentials which the EEG is ideally intended to record. The more frequent occurrence of blinks and eye movements in schizophrenic patients may lead to an artificial enhancement of slow frequency EEG power for schizophrenics and eventually "false significances". In contrast to this, we found more significant group differences when correcting for EOG artefacts than without it. This can be attributed to a very much inflated sample variability of the uncorrected EEG, due to the individually varying EOG power. We conclude that it may not be sufficient to select visually epochs for analysis that are considered artefact-free. Rather, one should monitor EOG artefacts and apply an appropriate correction. PMID- 1504113 TI - Subclinical hyperthyroidism: physical and mental state of patients. AB - We investigated whether subclinical hyperthyroidism [subnormal basal thyroid stimulating hormone (TSH) level, attenuated TSH response to thyrotropin-releasing hormone (TRH) stimulation, peripheral thyroid hormones within normal range] is accompanied by physical and mental changes. Thirty-five subclinically hyperthyroid patients (27 female, 8 male) were compared with 60 overtly hyperthyroid patients (51 female, 9 male) and with 28 euthyroid control patients (18 female, 10 male) with respect to physical symptoms, affective state, short term memory, ability to concentrate and psychomotor performance. Patients with subclinical hyperthyroidism ranged between the other two groups. The major difference between controls and subclinically hyperthyroid patients was an increase in frequency of nervous symptoms and symptoms due to an increase of metabolic rate and thermal regulation changes. The major differences between subclinically hyperthyroid and overtly hyperthyroid patients were psychomotor impairment and symptoms of increased metabolic rate. Self-ratings of affective state tended to be similar in patients with subclinical and overt hyperthyroidism. The ability to concentrate and short-term memory were not impaired in any group. Symptoms in patients with subclinical hyperthyroidism probably result from central changes which lead to attenuated TSH responses to TRH, or from elevated but still normal thyroxine levels, which possibly enhance the effect of catecholamines. PMID- 1504114 TI - Serum prolactin concentrations and epilepsy. A study which compares healthy subjects with a group of patients in presurgical evaluation and circadian variations with those related to seizures. AB - In 20 healthy subjects (10 female and 10 male) and 17 patients undergoing presurgical epilepsy evaluation with intracranial EEG electrodes, circadian variations of serum prolactin (PRL) were measured. A comparison between the peak values found in normals with the postictal rises in patients, led us to consider 700 microU/ml to be the threshold of diagnostic value and the observed rises above this level to be all induced by seizures. In order to assess the clinical value of this threshold, PRL was measured postictally in a further 30 patients with epilepsy and in 11 patients with psychogenic seizures. In none of the latter group did PRL rises exceed 700 microU/ml, while they did so in 39% of the complex partial seizures and in 80% of the tonic-clonic seizures. There was no significant difference with respect to sex (a rise over 700 microU/ml in 42% in male and in 55% in female patients). Based on the findings in 17 patients investigated by means of intracranial electrodes, we were not able to establish different criteria for different focus localisations: in 66% of both temporal as well as frontal lobe seizures the 700 microU/ml level was exceeded. As a trend, in the period preceding an epileptic seizure we found a slightly decreasing PRL level, whereas in healthy persons the PRL concentrations gradually increased in the 40 minutes before the maximum spontaneous peak was reached. PMID- 1504115 TI - [Results of radioiodine therapy in different forms of hyperthyroidism in relation to the planned dosage]. AB - The aim of this study was to assess the efficacy of radioiodine therapy (131J) in a large group (n = 925) of hyperthyroid patients treated at two major departments of nuclear medicine (Freiburg, abbr. FR, and Munich, abbr. M). 761 patients suffered from non-immunogenic hyperthyroidism (Plummer's disease) and the remaining 164 patients from immunogenic hyperthyroidism (Graves' disease). In these cases, radioiodine therapy using doses between 60 and 80 Gy proved ineffective, FR (80 Gy) recording 28% success and M (60 Gy) 54%. A dose of 150 Gy, however, is successful in more than 80% of the cases: FR 81%, M86%. However, the incidence rate of hypothyroidism increases consecutively with 150 Gy: FR 49%, M 62%. In patients suffering from Plummer's disease, the solitary autonomous nodule can be eliminated by radioiodine therapy (400 Gy) with a high rate of success (95%); the same applies to multinodular autonomous adenomas. The therapeutic concept applying a dose of 400 Gy to the total functional autonomous tissue (delineated by ultrasound) yields slightly better results (95%) than 150 Gy applied to thyroid gland (M88%, FR82%). This dosimetric compromise is a practicable alternative which is tolerably successful. In patients suffering from disseminated non-immunogenic hyperthyroidism, a dose of 150 Gy applied to the entire organ succeeds in 85% of the cases. The rate of hypothyroidism resulting from these dose recommendations is the lesser evil compared to residual or recurrent hyperthyroidism, since hypothyroid patients can be treated without any problem with thyroid hormones. PMID- 1504116 TI - [Reactive enlargement of cervical lymph nodes and cervical lymph node metastases: sonography (M/Q quotient) and computed tomography]. AB - Ranking of sonographic maximum/transverse diameter quotients was compared with the ranking of CT in respect of identification and exclusion of cervical lymph node metastases. Both sonography and CT are distinguished by a high degree of sensitivity in the imaging of cervical lymph node metastases. Sonography, with the assistance of the maximum/transverse diameter quotient, can differentiate between benign enlarged and non-enlarged lymph nodes on the one hand and cervical lymph node metastases on the other, with a safety of 95 per cent. CT can yield definite information regarding the tumour status only after contrast medium administration under the criteria of central hypodensity and peripheral marginal enhancement. CT is much less specific than the sonographic M/T quotient (66% vs 95%). Accuracy of sonography (94%) is clearly superior to that of CT (79%). PMID- 1504117 TI - [The mean optical density in x-ray pictures: measurement methodology, results and parameters]. AB - A simple testing method for defining the average density or the integral density of x-ray images is described. In a semiquantitative way the physicians in radiological offices can measure the proper integral density. The amount of scattered x-rays influences the integral density significantly. Proper values for testing the integral density of x-ray images are described. PMID- 1504118 TI - [FCR AC-1: prototype of a new generation of equipment for digital luminescence radiography (DLR)]. AB - The promising perspective to integrate the project-image-radiography into future picture archiving and communication systems (PACS) failed in medium terms because of high costs. A new generation of compact computed radiography systems (CR) facilitate the entry into storage phosphorus technique for routine application while future PACS-connection is still possible. In August 1990 the Institute of Diagnostic Radiology (University of Dusseldorf) received the first FCR AC-1 in Germany for clinical trials. The acquired experiences expounded by case reports emphasize the diagnostic benefit of this technique. The varying use of expandible FCR AC-1 systems is illustrated. PMID- 1504119 TI - [Focal spot sizes and the geometric unsharpness of mammographic equipment]. AB - The visibility of microcalcifications in mammography is limited, inter alia, by the dimensions of the focal spot of the x-ray tube. The user should be able to evaluate a given nominal value of the focal spot and to assess the effective size of the focal spot in his x-ray tube. Determination of the resolution with the help of the mammographic phantom suggested by the German DIN standards specifications requires special care. In the framework of the German Mammography Study, 45 mammography devices at different locations were tested with regard to their focal spot sizes. All devices complied with the acceptance test without any adverse comment, although--if judged objectively--only half of them have the resolution demanded by DIN standards. Consequently, in most of the cases the users are unaware of this, and the negative effects on the visibility of possibly present microcalcifications are often underestimated. The diagnostic importance of microcalcifications for the detection of breast cancer suggests, however, to abstain from devices which are only of limited usefulness in relevant mammography screening. PMID- 1504120 TI - [Typical findings and erroneous findings in SPECT-radioimmunoscintigraphy using 99mTc-labeled CEA antibodies in colorectal tumors]. AB - Radioimmunoscintigraphy with 99mTc-labelled monoclonal antibodies against Carcino Embryonic-Antigen (CEA) is increasingly accepted in the follow-up of patients suffering from colorectal carcinomas. However, interpretation of transversal, coronal and sagittal reconstructions of "Single Photon Emission Computed Tomography" radioimmunoscintigraphic studies is difficult due to physiological antibody accumulations and anatomical based variations of antibody distribution. In the following study we demonstrate therefore, the typical findings and "pitfalls" of radioimmunoscintigraphy with 99mTc-labelled CEA antibodies in comparison to findings in computed tomography, to help to avoid misinterpretations. PMID- 1504121 TI - [Radiologic diagnosis of osteoporosis. Current methods and outlook]. AB - Osteoporosis is defined as a decrease in bone mass and structural changes in bone leading to an increase in fractures. Early diagnosis as quantification of prophylaxis and treatment are of great interest. A number of non-invasive techniques are available for measuring bone mass at multiple sites of the skeleton. This article reviews basic methodology and developments in radiography as in x-ray or gamma photon absorptiometry, quantitative computed tomography, ultrasound velocity and attenuation and magnetic resonance imaging. Clinical applications of these methods are discussed. The still experimental use of ultrasound and MRI in assessment of bone-mineral content may also give information on bone quality. PMID- 1504122 TI - [Results of CT-guided puncture biopsies in the abdominal and pelvic regions]. AB - Results of 285 abdominal and pelvic CT-monitored biopsies are presented. 81.6% of the histological biopsies (n = 46) were evaluable (39.1% right positive, 43.5% right negative, 4.35% suspect). In 13% no definite findings were made. For the cytologic examinations and those due to an abscess 44.8% led to a right positive diagnosis and 23.8% gave a true negative finding. In 4.2% of the cases a suspect finding was given. 28% of all cytological evaluations were not definite. The complication rate was 1%. PMID- 1504123 TI - [The value of imaging techniques in the diagnosis of non-specific abdominal pain in young patients]. AB - In a retrospective study the use of imaging modalities in the diagnosis of non specific abdominal pain in patients under 31 years was evaluated. 253 patients with primarily non-specific abdominal complaints were analysed. For further investigation one of the following methods had to be applied: abdominal sonography and/or upper gastrointestinal tract roentgenograms and/or enteroclysis and/or barium enema. In 66% (167/253) of all cases abdominal pain remained non specific. Clinical history and physical examination led to the final diagnosis in 66/86 (76.7%) of patients with pathologic findings. 21/561 (3.7%) radiographic examinations revealed abnormalities of clinical importance. In 10/253 (4%) patients the final diagnosis could be established only with the help of radiologic and/or endoscopic examinations. The low efficacy of conventional radiology justifies the demand for a stricter indication in the young patient suffering from non-specific abdominal pain. PMID- 1504124 TI - [Congenital diaphragmatic hernia]. PMID- 1504125 TI - [Acute abdomen caused by inflammation of a Meckel's diverticulum containing a stone]. AB - Meckel's diverticula have a prevalence of approx. 2% in the population. About 90% of them are clinically inapparent. Usual complications are a perforation of ectopic gastric mucosa (possibly with intestinal bleeding), an invagination and a volvulus. Etiology is normally revealed only by surgical exploration. Calculi are rarely found in Meckel's diverticula, males being afflicted much more often than females. The enterolith consists of calcified residues of food. Unexplained abdominal symptoms with an ileus situation should also be considered a Meckel's diverticulum containing enteroliths. This is especially so, if there are unidentified calcifications visible on the abdominal X-ray. PMID- 1504126 TI - [The diagnosis of osteoporosis]. PMID- 1504127 TI - Quality of life and antihypertensive drugs in the elderly. AB - Hypertension is common in the elderly with estimates of around 10-20% showing a sustained level of pressure, either systolic (greater than or equal to 160 mmHg), or diastolic (greater than or equal to 90 mmHg) or both. The benefits of treating subjects with raised diastolic pressure was shown by the trials of the European Working Party on High Blood Pressure in the Elderly (EWPHE), the Hypertension in Elderly Patients in Primary Care (HEP), and the Swedish Trial in Old patients with Hypertension (STOP-Hypertension). Evidence for the benefit of treating isolated systolic hypertension in the elderly was provided in one trial (SHEP: Systolic Hypertension in the Elderly Program), and the results of two others are awaited. However, it is important to provide data on all treatment effects, including adverse reactions as well as benefits. In addition to traditional measures of mortality, morbidity and side effects, the quality of life in patients on antihypertensive treatment should be considered. The methods of measuring quality of life in trials is discussed, and some results presented. PMID- 1504128 TI - Accidents in the institutionalized elderly: injuries and consequences. AB - A total of 308 major and 519 minor accidents involving 588 patients occurred during one year at a somatic long-term care hospital and its associated nursing homes. In relation to the number of patients, the incidence of accidents was nearly three times higher in the nursing homes than in the hospital. The most prevalent injuries in female patients were fractures and hematomas, while open wounds were more frequent among male patients. Hip fractures were about as common in women as in men, while fractures of the extremities were three times more frequent in women. The majority of the accidents occurred during daytime, in the patient's room and in many cases soon after admission. Most of the injuries were caused by falls and in more than 90% no staff was present. Accidents were reported most frequently in October-December, and least often in July-September. Two thirds of the severely injured had to be transferred to an emergency hospital for surgery or other treatment. Patients who had had major accidents also had a higher mortality rate six months after the accidents as compared to a control group. The medical and functional consequences for the patients were considerable. Measures to reduce the number of accidents among geriatric patients are therefore urgently needed. PMID- 1504129 TI - Plasma lactoferrin as a marker of infection in elderly individuals. AB - To assess lactoferrin as a marker of infection, plasma lactoferrin (LF) levels were determined in elderly in patients with infection and compared with age- and sex-matched healthy and hospital controls and young healthy blood donors. The median LF level in infection (800 ng/mL) was significantly higher than in healthy elderly living in old people's home (300 ng/mL) or elderly hospital controls (298 ng/mL) (p less than 0.01 in each case). Plasma LF correlated significantly with elastase alpha-1-proteinase inhibitor complex (EPIC) (Rs = 0.8, p less than 0.01) and C-reactive protein (CRP) (Rs = 0.45, p less than 0.02), but not with erythrocyte sedimentation rate (ESR) or white blood cell counts. We conclude that plasma LF, like CRP and EPIC, is a marker of infection in elderly individuals. PMID- 1504130 TI - Orthostatic reactions in the 85-year olds. AB - Testing of the orthostatic reaction is recommended in the examination of elderly fallers. This test usually includes blood pressure and instantaneous heart rate measurement but is difficult to perform in very elderly people according to the guidelines suggested for younger subjects. One reason for this is that old people often stand up slowly. The use of a tilt table, which enables a rapid change in posture from recumbent to erect position, is tempting as it could provide a method for a better standardized test. To study the usefulness of the tilt table as well as the degree of orthostatic reaction in the very elderly, we examined a sample of 85-year olds who did not suffer from falls. All were tested both with the tilt table and with active rising. The drop in blood pressure was equal in the two test types, but the increase in heart rate was significantly larger in active rising. Many test subjects were afraid of the tilt table, and two developed cardiac arrhythmia, i.e., atrial fibrillation, during the test. In our opinion, active rising is the method of choice in old persons. While the test subjects were in unusually good health for their age and thus could provide a suitable reference group for this test, the systolic blood pressure dropped considerably in several during the test. Criteria and indexes developed for younger subjects are not useful, and different evaluation criteria should be developed for the very elderly. PMID- 1504131 TI - Dietary intake in a group of independent-living old people in Oslo. AB - Dietary intake (24-h recall), dietary supplementation practice and relative weight (BMI) were investigated in a random sample of 257 independent-living elderly persons above 75 years. The proportion of energy from fat was unfavorably high among women (41.7%), while diet nutrient density was similar for men and women. Mean intakes of vitamin D, thiamin and iron were below recommended levels. Use of a dietary supplement was more common among women (66%) than men (48%). Average daily energy intakes of 6.3 +/- 2.1 MJ in women and 7.3 +/- 2.2 MJ in men were just below the lower limit of the reference interval. Overweight was uncommon, while 14% of the women and 4% of the men had BMI below 18.5 kg/m2; 2% had a BMI below 16. We conclude that low energy intake is the major reason for potential malnutrition in this group of elderly persons; up to 10% may be at risk for energy deficiency, while 2% were chronic energy deficient. PMID- 1504132 TI - Age-related effects of ischemia, lidocaine and verapamil on overdrive-induced suppression of ventricular pacemakers in isolated rat heart. AB - The effect of age on ventricular automaticity in the isolated perfused rat heart was determined under different conditions. When the ventricle is electrically stimulated at a faster rate, drive cessation is followed by a temporary suppression of ventricular automaticity (overdrive suppression). The effects of ischemia, lidocaine and verapamil on overdrive suppression were studied in isolated perfused adult and senescent rat hearts with complete atrio-ventricular block, by monitoring ventricular escape rate and escape rhythm recovery time after 1 minute of overdrive at a constant multiple (x3) of the spontaneous rate. The results demonstrated that: 1) lidocaine decreases ventricular automaticity especially in senescent hearts; 2) verapamil does not modify ventricular automaticity in basal conditions in either adult or senescent hearts; 3) myocardial ischemia causes a reduction in ventricular automaticity and more markedly in senescent hearts; and 4) lidocaine exaggerates the effect of ischemia, while verapamil seems to antagonize its depressant effect more in adult than in senescent hearts. PMID- 1504134 TI - Successful aging and artistic creativity. PMID- 1504133 TI - Serotonin response in sweet-food craving Alzheimer's disease subjects. AB - Abnormal sweet-food craving may occur in subjects with Alzheimer's disease. This behavior may be due to abnormalities in the brain serotonin system. Fenfluramine stimulates the brain serotonin neurosystem, producing an increase in systemic prolactin. Using the fenfluramine stimulation test, brain serotonin system response was evaluated in 12 subjects with probable Alzheimer's disease. The subjects' caregivers completed questionnaires concerning subject food preferences and behaviors. Alzheimer's disease subjects with sweet-food craving were found to have a significantly higher response to fenfluramine than non sweet-food craving subjects. This preliminary study is limited by small sample size. Allowing for assumptions concerning central nervous system regulatory processes, the data suggest a possible role for the serotonin system in sweet-food craving in Alzheimer's disease. PMID- 1504135 TI - Neutrophil activation and function in health and disease. PMID- 1504136 TI - Granulocyte responses to cytokines. Basic and clinical research. PMID- 1504137 TI - Eosinophil activation and function in health and disease. AB - The emerging picture regarding the role of eosinophils in the immune response appears to be the following: IL-3 [in humans, (251)], and/or IL-1 [in the mouse system, (253)], then IL-5 and GM-CSF [which are secreted from activated T-cells at the inflammation sites or even from activated mast cells (346-348)] induce differentiation and proliferation of eosinophils in bone marrow. Other factors, such as PAF (303-309), C5a, soluble parasite products (259-261), or even IL-5 (139), serve as chemoattractants for eosinophils to the sites of allergic inflammation, usually around mucosal surfaces. Eosinophil survival and state of activation is enhanced by IL-5 (139). Eosinophils degranulate, thus releasing their toxic granule proteins by cross-linking Ig receptors, the most potent of which is sIgA, and the degranulation is enhanced by IL-5, IL-3, GM-CSF, and other factors or parasite products. Eosinophil degranulation can also be induced by complement, as well as PAF. The interplay of all these different mediators, and their effects on eosinophil function, is an integral part of the eosinophil's involvement in different disease conditions. Eosinophils appear to be involved in the pathophysiology of different diseases, in part, by releasing their toxic granule contents in tissues and causing tissue damage. PMID- 1504138 TI - Basophils and mast cells: piecemeal degranulation in situ and ex vivo: a possible mechanism for cytokine-induced function in disease. PMID- 1504139 TI - Regulatory effects of cytokines on myelopoiesis. PMID- 1504140 TI - Cytokine-stimulated emigration of granulocytes in vivo. PMID- 1504141 TI - Physiological studies with human leukocyte inhibitory factor. AB - LIF has been shown to be a potentially important activator of neutrophil function. By means of its dose-dependent dichotomous effects on chemotaxis, LIF can be predicted to both enhance the potency of chemotactic stimuli and promote the passive accumulation of PMN at inflammatory loci. Furthermore, LIF's stimulatory effects on both PMN- and endothelial cell-mediated adherence will promote the migration of neutrophils from the circulation to the inflammatory site. We have demonstrated LIF stimulation of fMLP, CR1, and CR3 expression and function, as well a stimulated Fc gamma RIII function. Through both receptor dependent and -independent effects. LIF produces increased target cell attachment, phagocytosis, respiratory burst activity, and degranulation. Together, these effects result in a significant increase in killing of both phagocytosed targets and extracellular targets. PMID- 1504142 TI - The biology of NAP-1/IL-8, a neutrophil-activating cytokine. PMID- 1504143 TI - Activation of neutrophils by interleukins-1 and -2 and tumor necrosis factors. AB - This review outlines evidence that IL-1, IL-2, and TNFs modulate neutrophil functions. These cytokines affect some or all of the following functions of the neutrophil: adherence, cell migration, respiratory burst, lysosomal enzyme release, and cell surface receptor expression. TNFs, especially TNF alpha, remains one of the most highly studied cytokine with respect to regulation of neutrophil function. TNFs are a direct stimuli for the neutrophil respiratory burst and weak stimuli of lysosomal enzyme release. The cytokines enhance cell adhesion and inhibit neutrophil migration. The TNFs augment the oxidative burst and lysosomal enzyme release response to a wide range of soluble and particulate cell stimuli. These changes in the cell seem to be closely correlated with the increased fungicidal, bactericidal, tumoricidal, and protozoacidal activity of the TNF-primed neutrophils. In contrast to TNFs, IL-1 and IL-2 inhibit neutrophil adherence, and this provides evidence that the cytokine family represents a regulatory system. Another form of regulation of TNF alpha and IL-1 neutrophil activating activity is by the release of inhibitors to these cytokines (58). We have evidence which shows that the soluble TNF alpha inhibitor (a cleaved product of the TNF alpha receptor) (59) binds and inhibits TNF from activating and priming neutrophils (60). Priming of neutrophils by TNFs involves surface receptor binding but is independent of protein kinase C system, pertussis toxin sensitive guanine nucleotide regulatory protein, and direct burst of respiratory activity. The translocation of cell surface receptors and constituents of the NADPH oxidase from stored vesicles may be the major mechanism of TNF-induced cell priming. PMID- 1504144 TI - Activation of neutrophils by granulocyte-macrophage colony-stimulating factor. AB - A hypothetical pathway of GM-CSF-induced signaling in human neutrophils is presented in Figure 4. The earliest postreceptor events leading to activation of cellular kinases and phosphorylation of c-raf on tyrosine and serine remain a mystery. It is conceivable that downstream events such as the production of LTB4 and PAF as well as other autocrine or paracrine activators of neutrophil activation function may be involved in neutrophil activation and priming, or they may be downstream events irrelevant in the signaling cascade. The association of GM-CSF signaling and G-proteins, PLD, c-raf, tyrosine kinases, and the Na+/H+ antiport remain poorly understood. PMID- 1504145 TI - The neutrophil respiratory burst mechanism. PMID- 1504146 TI - Mechanisms of host tissue damage by cytokine-activated neutrophils. AB - Although extensive investigations into the role of neutrophils and their products in tissue injury have been conducted, very little work has been carried out on the role of polypeptide cytokines in the regulation of neutrophil-mediated tissue damage. A range of cytokines are known to promote a wide variety of functions of the neutrophil, including neutrophil adhesion, surface receptor expression, ODRS production, and release of lysosomal constituents. Evidence has been presented to show that these products, either singly or in combination, cause tissue injury. At this stage, TNF alpha and TNF beta are cytokines which have been shown to regulate neutrophil tissue injury. From this work it is suggested that TNFs promote neutrophil-mediated tissue damage. PMID- 1504147 TI - Tumor necrosis factor stimulation of neutrophils for antitumor activity. PMID- 1504149 TI - Effects of hematopoietic growth factors on nonhematopoietic cells. PMID- 1504148 TI - Regulation of human eosinophil production and function by interleukin-5. PMID- 1504150 TI - Clinical trials of granulocyte-macrophage colony-stimulating factor for the treatment of aplastic anemia. PMID- 1504151 TI - Regulation of lipoxygenase enzymes in leukocytes. PMID- 1504152 TI - Activation of leukotriene production in granulocytes: effects on cell activation. PMID- 1504153 TI - HIV infection in children: epidemiological and diagnostic aspects. PMID- 1504154 TI - Treatment of bacterial vaginosis. PMID- 1504155 TI - The prevalence of hairy leukoplakia in HIV seropositive and HIV seronegative immunocompromised patients. AB - The prevalence of hairy leukoplakia was determined among 176 symptomatic HIV seropositive patients seen at the outpatient department of the Institute of Tropical Medicine in Antwerp, Belgium. Moreover, systematic tongue biopsies were performed during postmortem examination of 21 patients with AIDS, 100 HIV seronegative immunocompromised patients with haematologic or other malignancies and 100 HIV seronegative non-immunocompromised patients who died at the University Hospital Antwerp. Hairy leukoplakia was observed in 52 (29.5%) of the outpatients, but only in one (5%) of the AIDS patients in the postmortem study (P = 0.03). An explanation for this difference may be that significantly more AIDS patients who died had received either acyclovir or ganciclovir during the 3 months prior to the postmortem examination than the HIV seropositive outpatients during the 3 months prior to examination. Hairy leukoplakia occurred more often in Caucasian homosexual men with HIV infection (38%) than among heterosexual Africans with HIV infection (17%) (P = 0.06). Hairy leukoplakia was observed in none of the HIV seronegative patients. PMID- 1504156 TI - Sexual behaviour related to the spread of sexually transmitted diseases--a population-based survey. AB - Behavioural patterns pertinent to the spread of sexually transmitted diseases (STD) were assessed in a random sample population study in Sweden. From a sample of 1150 individuals aged 16-31 years, 768 (68%) completed a questionnaire on past and present sexual contacts. Response rate was highest in youngest and oldest age groups. Median age at first intercourse was 16.4 years for women and 17.1 years for men; the woman's partner at first intercourse was a median of 2 years older; men chose partners of the same age for first intercourse. The time to second partner was a median of 2 years; number of lifetime partners increased with one new partner for 2.5 years. Condoms were more frequently used in younger age groups. In all age groups, 5-10% of individuals reported a high-risk behaviour for the spread of STDs. PMID- 1504157 TI - Eight year prospective study of HIV infection in a cohort of homosexual men- clinical progression, immunological and virological markers. AB - Three hundred and fourteen homosexual/bisexual men at risk for human immunodeficiency virus (HIV) infection (170 seroprevalent HIV-positive, 144 seronegative) were prospectively studied over 8 years to assess rates of HIV infection and disease progression, in conjunction with cellular and HIV serological markers. In HIV-positive subjects, CD4+ lymphocyte counts rose strikingly during the period surrounding seroconversion, then fell progressively over the intervening period to a mean level of 300 cells/mm3 when AIDS developed. Changes in CD8+ lymphocyte counts were less consistent. The trend for HIV serological markers over the study period was of progressive decline in the proportion of subjects with anti-p24 antibody, associated with an increase in the proportion of subjects with detectable HIV antigenaemia. However, only 45% of subjects tested had lost anti-p24 antibody by the time of AIDS diagnosis, and HIV antigen was detectable up to 4 years before this. Different HIV serological patterns were also observed in subjects presenting either with Kaposi's sarcoma or opportunist infections. Our data support the continued use of cellular and virological markers in the evaluation of HIV disease; however, the variability observed in this study highlights their limited ability in predicting specific clinical events. Care should therefore be taken to encompass both clinical and laboratory information in the medical assessment of the HIV-infected individual. PMID- 1504158 TI - Trends in sexual behaviour in a cohort of homosexual men: a 7 year prospective study. AB - A cohort of homosexual men at risk for human immunodeficiency virus (HIV) infection were studied prospectively over a 7-year period (1982/88) to assess trends in sexual behaviour and amyl nitrite intake. During the period, there were dramatic declines in the proportion of HIV seropositive and seronegative subjects reporting multiple casual partners for anal intercourse, unprotected anal intercourse and recreational use of amyl nitrite. Reported rates of orogenital intercourse remained the same during the period, whilst the total number of seroconversions fell from 17 for the period 1982-84 to 8 for 1985-88. High-risk sexual and related social behaviour among homosexual men, as assessed by patterns of anal intercourse behaviour and nitrite intake, changed over the 7-year period, with the greatest changes apparent before the widespread availability of HIV antibody testing and public education campaigns. This highlights the effectiveness of peer-group and community-based programmes in modifying the sexual behaviour of their members. PMID- 1504159 TI - Strain characteristics and antibiotic susceptibility of isolates of Neisseria gonorrhoeae causing disseminated gonococcal infection in Australia. Members of the Australian Gonococcal Surveillance Programme. AB - The auxotype (A) and serovar (S) distribution and antibiotic and serum sensitivity of 22 strains of Neisseria gonorrhoeae isolated from blood and joints were determined. With one exception, these strains from disseminated gonococcal infections (DGI) belonged to one of 4 serovars of the IA serogroup and were resistant to killing by normal human serum. The auxotype distribution of these Australian strains differed significantly from that reported elsewhere in that 17 of the 22 isolates were proline requires, but none were of the AHU auxotype. This lack of the AHU auxotype in the DGI strains in Australia was explained by the virtual absence of AHU requirers in a sample of 1560 mucosal strains isolated in Sydney and Darwin from 1987 to 1990. The A/S distribution of these mucosal isolates also helped to account for the low (0.12) percentage of DGI strains in isolates examined by the Australian Gonococcal Surveillance Programme (AGSP) from 1981 to 1991, and the differences in the rates of DGI in Sydney (0.08%) and Darwin (0.87%). There was a relative lack of the IA serogroup strains which are mostly responsible for DGI in the mucosal isolates from Sydney (15% of all strains) but a higher proportion of these serovars (40%) in the Darwin sample. There were 46 cases of DGI in data from the AGSP, 29 of these being women. Seven of the cases diagnosed in Australia were infected with penicillinase-producing gonococci suggesting that antibiotics other than the penicillins should now be used for this condition in this region. PMID- 1504160 TI - Megestrol acetate vs cyproheptadine in the treatment of weight loss associated with HIV infection. AB - Two appetite stimulants, megestrol acetate and cyproheptadine were administered in a randomized trial to 14 patients who had no evidence of opportunistic infection or malabsorption but were wasted (had lost more than 5 kg body weight) as a result of human immunodeficiency virus (HIV) infection. Energy intakes were calculated from a 7 day weighed dietary record. Mean energy intakes per kilogramme body weight were similar in both treatment groups (greater than 34 kcal/kg) and were higher than that in well British males. Energy intakes increased by just over 500 kcal during both treatments, but fell to pretreatment levels after therapy. Patients in both treatment groups gained a moderate amount of weight. Megestrol acetate was associated with impotence in 4 patients. Insufficient calorie intake alone is not a common cause of wasting associated with HIV and the role of appetite stimulants is likely to be limited. PMID- 1504161 TI - Prevalence of HIV-2 infection in a family planning clinic in Lisbon. AB - A significant proportion (10%) of notified AIDS cases in Portugal are due to HIV 2 infection as a result of the close connections of Portugal with Western African Countries (ex-Portuguese colonies) where there is a high HIV-2 seroprevalence. We conducted a seroepidemiological study of HIV-1 and HIV-2 infection in 1400 women attending family planning and antenatal clinics in a health centre in Lisbon with the objective of analysing whether there was evidence of HIV-2 spread in this population. The seroprevalence for HIV, as determined by ELISA and confirmed by Western Blot, was 0.42% (6 cases) and 50% of these were of HIV-2 infection. Analysis of the epidemiological inquiries reveals that out of the 6 seropositive cases, only one was a drug addict (HIV-1) and another a western African black woman (HIV-2). The other 4 cases (2 HIV-2 and 2 HIV-1) were white Portuguese women with no history of travelling to Africa or previous blood transfusions, and the only risk factor was a history of multiple sexual partners (in 3 out of 4). PMID- 1504162 TI - Empirically treated Pneumocystis carinii pneumonia in London, 1983-1989. AB - For 227 episodes of Pneumocystis carinii pneumonia (PCP) treated at St Mary's between 1983 and 1989, factors predictive of fatal outcome were age, haemoglobin levels, peripheral lymphocyte count and alveolar-arterial oxygen gradient. Case fatality for the 47 empirically-treated episodes was significantly higher compared with the 180 cytologically proven episodes (55% vs 18%, chi 2 = 25.7, P less than 0.0001). Case fatality for episodes which could not be bronchoscoped was significantly higher compared with bronchoscopy negative cases (66% vs 25%, chi 2 = 4.5, P less than 0.05). Predictive factors for fatal outcome differed significantly for cases which could not be bronchoscoped and cytologically proven cases: haemoglobin level (10.7 g/dl vs 12.0 g/dl, P less than 0.001), lymphocyte count (0.64 x 10(9)/l vs 0.87 x 10(9)/l, P = 0.05) and oxygen gradient (77.7 mmHg vs 58.9 mmHg, P less than 0.02). Such differences were not observed between bronchoscopy negative and cytologically proven cases. Case fatality decreased significantly over time (b = -0.39, SE = 0.14, P less than 0.05). Total and non fatal first time episodes displayed an inverse relationship between oxygen gradient and time (r = -0.22, P less than 0.006 and r = -0.24, P less than 0.01, respectively). Mean oxygen gradient of fatal episodes for sequential years increased significantly from 73 mmHg in 1983 to 102 mmHg in 1989 (r = 0.92, P less than 0.01). This suggests that medical intervention as well as presentation with less severe disease both contributed to improved case fatality over time. PMID- 1504163 TI - Reduction in needle sharing among community wide samples of injecting drug users. AB - Evidence of reduced levels of needle sharing among injecting drug users (IDUs) has largely been confined to IDUs attending needle exchanges or receiving treatment. In this paper we present the results of a serial cross-sectional study of needle sharing conducted in Glasgow using a multisite sampling strategy. Of the estimated 9400 IDUs in the city, 503 were interviewed in 1990 and 535 in 1991. The proportion of IDUs reporting injecting with, or passing on used needles and syringes in the last 6 months fell significantly as did the number of individuals from whom equipment was received or passed on to. The impact of this level of sharing has been limited in terms of HIV transmission; the prevalence of HIV among the 1990 sample was 2.0% and 1.1% for the 1991 sample. However, the fact that third of IDUs in Glasgow continue to inject, even occasionally, with used equipment gives cause for concern in view of the other pathologies known to be associated with poor injecting hygiene. PMID- 1504164 TI - Bordetella bronchiseptica recurrent bacteraemia in the setting of a patient with AIDS and indwelling Broviac catheter. PMID- 1504165 TI - Staphylococcus aureus psoas abscess in a patient with AIDS. PMID- 1504167 TI - AIDS Literature Index. PMID- 1504166 TI - Hutchinson's triad in a 9-year-old girl. PMID- 1504168 TI - An emphasis on solutions rather than problems. PMID- 1504169 TI - Do we care enough to attempt change in American Indian alcohol policy? PMID- 1504170 TI - Alcohol policy considerations for Indian people. PMID- 1504171 TI - Alcoholic beverage control policy: implementation on a northern plains Indian reservation. PMID- 1504172 TI - Alcohol policy considerations for Indian reservations and bordertown communities. AB - For some topics, particularly in public health, summaries are dangerous because they may create the idea that a single or simple solution exists. This topic is one where a summary can create a false expectation of simplicity. There is no simple or easy solution to the problem of alcohol abuse in any community, especially reservation and bordertown communities in the western United States. The solution is complex, it must be comprehensive, and it will take a great deal of effort over time to reduce alcohol and substance abuse in any individual community. Indian communities must develop a comprehensive, consistent, and clearly defined alcohol prevention/intervention policy. Such a policy must utilize a systematic, public health approach that considers the physical, mental, and social well being of each and every individual within the region. It must address all types of problematic alcohol consumption, from sporadic alcohol consumption (light and heavy) to regular alcohol abuse and chronic alcoholism, for the problems found in Indian and bordertown communities arise from a variety of different drinking patterns. Presented in this paper are a large number of policy and prevention options that have been used successfully in human societies in various parts of the world and in the United States. The intent of the paper is to present and describe the variety of options for addressing alcohol problems that have been found to be of value in the control and reduction of alcohol abuse and related problems. The three broad categories of approach are: controlling the supply of alcoholic beverages through statute and regulation; shaping drinking practices directly; and reducing the physical and social environmental risks. Indian tribal councils and Native communities can, if they so desire, consider, debate, and enact any or all of these measures. The important issue is that they should be aware of these ideas for prevention and consider them carefully. If the preventive measures described here can be applied systematically and reasonably within the social and cultural contexts of a Native community, then the ultimate result should be positive. Readers are encouraged to read this paper carefully, to study the tables and figures, and if more detail is desired, to consult some of the many references found in the back. Comprehensive and positive alcohol policy has been ignored for too long in Indian country, and the resultant toll in morbidity, mortality, and suffering is too high. This paper presents the ingredients for a comprehensive policy. Each community need to work its own recipe. PMID- 1504173 TI - Native alcohol policy options. You've been given a map: blazing a trail is up to you. PMID- 1504174 TI - Alcohol policy considerations in American Indian communities: an alternative view. PMID- 1504175 TI - Commentary on "Alcohol policy considerations for Indian reservations and bordertown communities". PMID- 1504176 TI - The need for community consensus as a condition of policy implementation in the reduction of alcohol abuse on Indian reservations. PMID- 1504177 TI - Community development as context for alcohol policy. PMID- 1504178 TI - The next twenty years of prevention in Indian country: visionary, complex, and practical. PMID- 1504179 TI - Much remains to be done. PMID- 1504180 TI - Histochemical probing of potato periderm with neutral red: a sensitive cytofluorochrome for the hydrophobic domain of suberin. AB - A technique is described which uses the lipid fluorochrome neutral red as a cytochemical probe to detect the hydrophobic domain of the ligno-suberin matrix in native and wound periderm of potato tuber. Toluidine blue O is used as a counterstain to quench autofluorescence. The neutral red technique appears to be specific for the hydrophobic/lipid domain of suberin and is significantly more sensitive than Sudan III and IV. The fluorochrome was extensively used on paraffin-embedded tissue with excellent results but also worked on freehand sections of fresh periderm tissue. In tuber tissue undergoing wound-healing, the pattern of suberin fluorescence obtained with the neutral red probe was identical in specificity to the color pattern obtained with Sudan III/IV, but somewhat different than that observed when berberine was used. Results obtained with the neutral red probe and berberine probe visually demonstrated that during ligno suberin biosynthesis, the depositions of hydrophobic/lipid and phenolic/lignin like components in potato tuber periderm were separate processes. The deposition of these components does not necessarily require their simultaneous presence because the fluorescence from these probes showed that the components were not consistently present together on the cell walls. PMID- 1504181 TI - Distinctive uptake of neutral red by mitotic cancer cells. AB - Neutral red stains both normal and cancer mitotic cells, but uptake by living mitotic cancer cells is distinctly higher than in normal cells. This new approach to cancer cell identification is demonstrated in 4 established tumorigenic cancer cell lines: human skin epidermoid carcinoma A431, mouse Cloudman malignant melanoma, human oral epidermoid carcinoma and rat hepatoma. Human Chang liver cells served as normal controls. With epidermal growth factor (EGF) prepulse, neutral red uptake is dramatically enhanced. The possibility of a causal relationship with M-phase specific phosphorylation is discussed. PMID- 1504182 TI - A method for histological examination of undecalcified teeth. AB - A method is presented for histological examination of undecalcified ground sections of tooth roots affected with periodontal disease. The roots were placed in Karnovsky's fixative overnight, postfixed in 2% buffered osmic acid, and dehydrated in an ascending series of ethanol. The specimens were then infiltrated with propylene-oxide and Epon-Araldite resin, embedded in Epon-Araldite, and sections were prepared using a cutting and grinding system. The resulting ground sections were 8-12 microns thick. The sections were allowed to air dry at room temperature. When thoroughly dried, a coverglass was applied using resinous mounting medium DPX. The specimens were examined by phase-contrast microscopy. The method is useful for simultaneous examination of mineralized dental tissue and bacterial morphotypes covering the root surface of teeth involved with periodontal disease. PMID- 1504183 TI - Macroscopic sectioning of undecalcified tissues. AB - An inexpensive laboratory apparatus designed to section undecalcified teeth and bone has been constructed. It consists of an electric motor with a mandrel bearing a carborundum sectioning disk centered within a Plexiglas enclosure. A coolant flows from a reservoir positioned in the upper portion of the Plexiglas enclosure to prevent desiccation or burning of the tissues. Undecalcified tissue can be cut into a series of thin, 0.5-1 mm slices to facilitate studies of pulpal enzymes, tooth morphology and design of dental cavity preparations. PMID- 1504184 TI - [The 150th anniversary of anesthesia. 1992-1996: a space of 5 years for evaluating the history of anesthesia in the German-speaking world]. PMID- 1504185 TI - [Alternative mechanical autotransfusion. Hemofiltration vs. hemoseparation]. AB - The effect of haemoconcentration of shed blood from operative field during vascular surgery by either centrifugation (cell separation, n = 10) or haemofiltration (n = 10) was investigated. Interest in this in-vitro-study was focused on the quality of the blood concentrated. Various parameters were measured in the patient (before onset of anaesthesia), and in the blood after suction from operative field: 1. shed blood, 2./3. after haemoseparation/ filtration. Both procedures were easy to perform but haemofiltration produced whole blood quicker than the cell-separation technique (1.2:3.0 minutes). All patients had normal parameters. Suction led to an activation of plasma coagulation and an increase of free haemoglobin and elastase. Haemoseparation in contrast to filtration led to an elimination of thrombocytes, elastase, free hemoglobin and all proteins including antithrombin III and fibrinogen; concentration of red cells was more pronounced after separation (hct 55 vs. 35%). Heparin reduction was better after separation but plasma-heparin-levels were in a tolerable range after both procedures (0.21 vs. 0.75 U/ml). None of the procedures was followed by the appearance of activated clotting factors (F XII a). The data presented demonstrate that haemofiltration may be an alternative in intra- and postoperative autotransfusion. The particular advantage of this method is the preservation of plasma proteins after concentration procedure thus avoiding the need for additional application of fresh frozen plasma in patients with significant blood loss. PMID- 1504186 TI - [Autologous transfusion--organization and results of preoperative blood donation by heart surgery patients]. AB - This study presents our preoperative autologous blood donation programme that is in use since 1987. 246 patients of cardiothoracic surgery participated in this program. 77% of all patients had preoperative concentrations of haemoglobin above 12g/dl despite frequent donations. 36.5% of patients were transfused exclusively with their own blood products. Reduction of homologous blood transfusion has been achieved with second preoperative plasmaphereses and more restricted indication for blood transfusion. More blood donation could be performed with application of erythropoietin resulting in more frequent preoperative blood donations. PMID- 1504187 TI - [The effect of blood conservation techniques on the plasma concentration and elimination of midazolam in patients undergoing hip joint surgery]. AB - OBJECTIVE: The question was to evaluate whether haemodilution or intraoperative autotransfusion have an influence on plasma levels and clearance of midazolam. DESIGN: The study was designed as a prospective evaluation of patients with total hip joint replacement. The patients received neuroleptanalgesia supplemented with enflurane. After induction of anaesthesia with midazolam (0.1 mg/kg body weight) haemodilution procedure was started. During surgery a cell saver was used for blood salvage. In the recovery room drainage blood was also being processed by a cell saver. PATIENTS: The study includes 10 patients belonging to ASA-group II with an average weight of 79.4 kg (53-100 kg), at an average age of 57.9 years (44-68 years). MEASUREMENTS AND MAIN RESULTS: Midazolam was measured in patient blood and in autologous blood units by gas chromatography. 151 micrograms of midazolam, i.e. 1.8% of the initial dose was retransfused in hemodilution blood. By processing of blood in the cell saver, 99.5% of the amount of midazolam found in the sample unit was eliminated. The maximum quantity was 5.5 micrograms in the washed autologous red cell concentrate. CONCLUSION: Considering the analytic limit of 2 micrograms/l of midazolam in plasma, retransfusion of autologous blood cannot influence the plasma concentration of midazolam. Therefore, there is no risk of re-sedation in retransfusing autologous blood postoperatively. PMID- 1504188 TI - [The history of anesthesia in thoracic surgery. The problem of pneumothorax, intubation, one-lung ventilation]. PMID- 1504189 TI - [Polytrauma following a fall from a great height. The injury pattern and the intensive medicine aspects]. AB - We report on 10 polytraumatised patients who were treated in an ICU after a free fall injury. The injury pattern of these patients proved to be relatively uniform. Brain oedema occurred in many victims. Remarkable was the fact that 8 out of 10 patients developed a pneumothorax, but only three of them had rib fractures on the same side. All patients suffered from fractures of the extremities with the lower extremities being affected more often. Abdominal injuries were not of importance. PMID- 1504190 TI - [Checking the precision of capnometers]. AB - Capnometry, i.e. measurement of CO2 concentration (cCO2, vol%) and calculation of the respective CO2 partial pressure (pCO2, mmHg), is simple to apply, but the user must understand its principles of operation in order to appreciate its power and its limitations. However, sidestream capnometers use to dry the humidified respired gas (37 degrees C, pH2O 47 mmHg) for methodological reasons, thus increasing pCO2 by ca. 6% which, in turn, requires correction. With infrared spectroscopy, overestimation of pCO2 in presence of N2O and underreporting of pCO2 in presence of O2 also require to be corrected. These require either knowledge of the respective gas concentrations (mainstream analyzers) or adequate (i.e. correct) measurement (some sidestream capnometers). Changes in barometric pressure (pB) must be also either known or be measured automatically. Evaluation of the precision of capnometers must therefore focus on, (1) the possible pH2O correction, (2) the possible effects exercised by O2 and N2O, and (3) the possible dependence on barometric pressure. Two mainstream (Capnolog D/Drager; Sirecust 404-1/Siemens) and eight sidestream capnometers (AGM 1304/Bruel & Kjaer; SARAcap A. G. and SARA-trans/Biomedical Systems/Hellige; Capnomac and Normocap 200/Datex/Hoyer; CO2 Monitor/Drager; Nellcor N-1000/Nellcor/Drager; Multinex/Datascope) were investigated. Dry and humidified gases (37 degrees C) of defined composition in respect of CO2, O2, N2, N2O, and H2O, were used for evaluation. The results prove reproducibility of ca. =/- 1 mmHg for the 10 capnometers within the 30-50 mmHg pCO2 range.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1504191 TI - [Measurement artifacts in Gaeltec intracranial pressure monitors due to radio waves from personal beeper systems]. AB - Artifacts were observed when using epidural pressure monitoring systems (Gaeltec ICT/B Titan). These were produced by radio waves from our beeper system. A non existing electromagnetic shield of the Gaeltec-measuring amplifier SN 10/11 could be found as the cause. The artifacts can lead to therapeutical errors. PMID- 1504192 TI - [A new single-lumen endobronchial tube for artificial respiration following pneumonectomy in thoracic surgery]. AB - If a patient who has undergone a major resection such as a pneumonectomy or radical pneumonectomy develops during the postoperative period respiratory failure requiring mechanical ventilation, this may cause problems with the respirator treatment. It is of particular interest that the newly sutured bronchus stump can be protected from high ventilation pressures. Until now, patients who have undergone pneumonectomy have been ventilated using a single lumen tube or a double lumen tube (Table 1). A major complication often leading to death is a bronchial stump dehiscence giving rise to a bronchopleural fistula on the operated side due to aggressive mechanical ventilation. Therefore, we developed a new single lumen endobronchial tube (produced by Willy Rusch AG, W 7050 Waiblingen, Germany, Cat.No. 115900) for the mechanical ventilation of pneumonectomised patients (Fig. 1). The sutured bronchial stump lies between the bronchial and tracheal cuff (Fig. 2) and for that reason is not exposed to any increased ventilation pressure. This new tube contributes to a lower complication rate in mechanically ventilated patients after pneumonectomy. PMID- 1504193 TI - [Tubal malpositioning as a cause of tubal cuff hernia]. AB - Airway obstruction of endotracheal tubes may occur during general anaesthesia. A case is reported where endobronchial intubation and inflation of the cuff caused herniation into the left bronchus before the malpositioning had been corrected. This led to a cuff herniation that caused airway obstruction at the end of anaesthesia. The regional overinflation of the tubes cuff could be reproduced by a model by other tubes of the same type. Malpositioning of endotracheal tubes may cause cuff herniation that potentially leads to acute airway obstruction. PMID- 1504194 TI - [Historical vignette (1). Crawford W. Long]. PMID- 1504195 TI - [Comment on the original article: Electrophysiologic studies of polyneuropathy in intensive care patients]. PMID- 1504196 TI - Real-time measurement of microvascular dimensions using digital cross-correlation image processing. AB - A real-time automatic digital image-processing algorithm was developed for measuring microvascular dimensions. Using video microscopic images of the vasculature, the video images are digitized and analyzed using contrast enhancement, frame averaging, and pattern recognition, rather than edge detection. Performance of the algorithm was evaluated for second- and third-order vessels surrounded by the complex interfering features of in vivo skeletal muscle. Graded diameter changes and vasomotion were induced with pharmacological agents. Data obtained by auto-tracking agreed with data obtained by traditional manual methods of measurement. These findings indicate that a pattern recognition algorithm based on cross-correlation analysis provides a highly accurate method for real-time automatic tracking of microvessel diameters. PMID- 1504197 TI - Heme-containing proteins suppress lymphatic pumping. AB - Red blood cells (RBCs) and lysate products (erythrolysate) are consistently observed in lymph draining inflammatory reactions and from tissues subjected to trauma or surgical procedures. We determined previously that erythrolysate modulates lymphatic pumping by altering the pressures over which the lymph pump is active. The purpose of this study was to test the hypothesis that oxyhemoglobin was the active material within erythrolysate. To quantitate lymphatic pumping, bovine lymphatics were suspended in an organ bath preparation with the vessels cannulated at both inflow and outflow ends. By raising the heights of the Krebs reservoir and the outflow catheters appropriately, a transmural pressure could be applied to the vessels. This procedure stimulated pumping activity. Erythrolysate was prepared from sheep RBCs by lysis in Tris buffer and a portion of this was purified by column chromatography using DEAE Sephadex A-50. Both the purified hemoglobin (10(-5) M) and crude erythrolysate (the latter diluted appropriately in Krebs solution to contain 10(-5) M hemoglobin) reduced lymphatic fluid pumping approximately 70% over a period of 2 h. To determine whether this activity was due to the heme or the protein portion of the molecule, we compared the activity of purified oxyhemoglobin with that of its oxidized methemoglobin derivative. This was achieved by conversion with potassium ferricyanide. Methemoglobin was inactive, suggesting that the heme portion was important for the lymphatic effect. Further confirmation of this observation was provided by experiments with myoglobin which was purified from sheep heart. Oxymyoglobin, which shares an identical heme but has a different protein component, inhibited lymphatic pumping, when tested on the bovine lymphatics.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1504198 TI - Altered aortic production of 6-keto-prostaglandin F1 alpha from aldosterone-salt hypertensive rats. AB - Supersensitivity of vascular smooth muscle to catecholamines in aldosterone-salt hypertensive rats appears to reside beyond the alpha 1-adrenoceptor. The objective of this study was to assess the norepinephrine-stimulated production of arachidonic acid metabolites by aorta from control-salt rats (CSR) and aldosterone-salt hypertensive rats (AHR) to determine whether these metabolites might contribute to the altered sensitivity. Norepinephrine increased in a time dependent manner the production of 6-keto-prostaglandin F1 alpha (6-keto-PGF1 alpha), thromboxane B2 (TXB2) and prostaglandin E2 (PGE2) by the aortae of CSR. Production was an alpha 1-adrenoceptor-mediated event since it was inhibited greatly by prazosin but not by yohimbine. Basal values of the metabolites did not differ for 6-keto-PGF1 alpha and TXB2, but were higher in AHR compared with CSR for PGE2. The norepinephrine concentration-response curve for 6-keto-PGF1 alpha was shifted significantly to the right for the AHR group compared with CSR (EC50 = 2.30 +/- 0.55 and 0.29 +/- 0.07 microM, respectively) indicating decreased production of norepinephrine-stimulated prostaglandin I2 in AHR. The norepinephrine-stimulated TXB2 concentration-response curves for AHR and CSR were similar. Indomethacin was an effective inhibitor of TXB2 and 6-keto-PGF1 alpha production in both. Norepinephrine-stimulated contraction was significantly affected by indomethacin in CSR but not in AHR. Whereas we observed an attenuation of a norepinephrine-stimulated vasodilatory substance in aortae of AHR compared with CSR, the effect of attenuation on vascular activity is presently unclear. PMID- 1504199 TI - l-NG-nitro-arginine methyl ester in the anesthetized rabbit: venous vasomotion and plasma levels. PMID- 1504200 TI - [Narcolepsy]. PMID- 1504201 TI - [Clinical activity and serum immunoglobulin concentrations in patients with ankylosing spondylitis]. AB - Several authors have suggested that immunoglobulin A plays a pathogenic role in ankylosing spondylitis. We have determined the levels of immunoglobulins in 30 patients, observing higher levels than in control patients (248 vs 176 mg/dl); p less than 0.01) and a relation between the increase of immunoglobulin A and the presence of clinical activity in the subgroup of patients B27-negative (163 vs 398 mg/dl, p less than 0.005), but not in B27-positive patients. We think that these e results support the hypothesis that ankylosing spondylitis is an heterogeneous disease, with different pathogenic mechanisms depending on the presence or absence of the serological marker HLA-B27. PMID- 1504202 TI - [Intralymphatic administration of adoptive (LAK) immunotherapy in the treatment of patients with metastatic cancer resistant to conventional therapies]. AB - Between January, 1990 and May, 1991, we administered LAK immunotherapy using the intralymphatic route to 25 patients with metastatic cancer resistant to conventional therapies. In the preparation of the immunotherapy, we followed the technique described by Pizza G. et al. The age of our patients ranged between 50 and 75 years and their Karnofsky's indexes were above 70%. The histological type of the metastasis were determined by Rx, ECO and/or CAT before and after the administration of the immunotherapy. In the intralymphatic administration, we followed the technique described by Pizza G. et al. The immunological therapy was administered on days 1, 21, 90 and 111 and the clinical response was assessed by RC, RP, EE and F. The immunological behaviour of the host was assessed through the determination of lymphoid populations (CD2, CD4, CD5 and CD8) and cytolytic cells were studied with monoclonal antibodies CD and CD16. Such immunological study was carried out before the administration of each immunotherapy series. In 7 out of 25 patients (28%), we were able to administer the four LAK series. Such patients were subsequently studied, observing that, although tumoral lesions did not increase in size, they did not disappear and, thus, they were classified as clinically stable. Clinical and analytical toxicity was null. The immunological study did not show any statistically significant changes and the activity of cytotoxic cells (NK) was not modified. PMID- 1504203 TI - [Incidence of typhoid fever in our environment. Analysis in Guipuzcoa]. AB - Based in 184 cases of Typhoid Fever bacteriologically demonstrated in the past 14 years (greater than 90% of all cases registered in the whole province), we have observed that, with the exception of some epidemic outbreaks, the disease has been constantly present during all these years, with a higher incidence between August and November. Salmonella typhi infected primarily young adults, its distribution being similar to the one among the general population. 49% of cases were males. The estimated incidence rate of the disease during this period was 2 3 per 100,000 population. A seroepidemiological study among healthy women with ages between 20 and 40 years showed a seroprevalence of anti-H:d antibodies greater than or equal to 1/40 of 1%. Although the epidemiological situation of Typhoid fever in our environment is not as bad as it has been referred in reports and textbooks, an effort is needed to situate the problem at the appropriate level, given our geographical situation and our economical development. PMID- 1504204 TI - [Narcolepsy and alopecia areata: a new association?]. AB - We here present three cases with Alopecia Areata and Narcolepsy, an association we believe to be hitherto undescribed. Narcolepsy is a low-frequency (0.5%) disorder. It is now accepted that the majority of patients with narcolepsy are DR2 positive. Alopecia Areata is a disease whose incidence in Caucasian population is between 0.05% and 1%. In both diseases there is a set of common data and the origins of the two diseases have been related to an autoimmunity mechanism. In both, a higher than normal incidence of diabetes has been recorded, together with a predominant HLA type pattern. We believe that this association is not casual although epidemiological studies are needed to test our working hypothesis. PMID- 1504205 TI - [Non-specific digestive ulcers and Behcet's disease]. AB - We present a 56-year-old patient with episodes of recurrent abdominal pain and constitutional syndrome, whose evolution was complicated by mucous ulcers in mouth, esophagus, anus and ileocecal valve, as well as occasional aphthae in scrotum. All these clinical signs are compatible with a Behcet's disease with relevant digestive manifestations. PMID- 1504206 TI - [Tuberculosis caused by Mycobacterium bovis: apropos of 2 cases]. AB - Infection by Mycobacterium bovis is currently a rare form of tuberculosis in developed countries, being its incidence lower than 1%. Its main mechanism of transmission is through the ingestion of contaminated milk. In this paper, two cases of tuberculosis by Mycobacterium bovis are described, one of lymphatic location by endogenous reactivation and another of pulmonary location, probably by a primary infection acquired through the inhalation route. We stress the risk of transmission of the disease through the respiratory route from infected animals and by person to person contagion. PMID- 1504207 TI - [Previous dissociative psychiatric disorder and status epilepticus in a case of acute HIV infection]. AB - We described an 18 old homosexual man who after 5 days developed a neurologic picture associated with Human Immunodeficiency Viruses (HIV) seroconversion. The patient had developed a dissociative psychiatric disorder 6 months before, and after resolution of the acute neurologic disease a mild neuro-psychiatric disorder remained. After mononucleosis-like syndrome of three weeks, the patient developed a meningo-encephalitic process 48 h post admission. He evolved with tonic seizures and twilight state and was admitted into Intensive Care Unit because of epileptic status and deep coma. Evolution was favourable after 72 h of treatment with acyclovir and antiepileptic drugs. Laboratory data showed an inverted T4/T8 ratio and seroconversion to HIV-antibodies and p24-antigen both in serum and CSF. These observations confirm the existence of psychiatric as well neurological alterations in acute HIV infection, and also the significance of p24 antigen and Western-Blot in serum and CSF in showing the seroconversion profile. PMID- 1504208 TI - [Magnesium: therapeutic usefulness in emergency situations]. AB - Magnesium has been a forgotten cation from the therapeutical point of view, given that, although its properties began to be known more than a century ago, its use has been always empirical or isolated. With respect to its use in emergency situations, in addition to correcting its deficit and using it for the treatment of hypercalcemia and hypopotassemia, it is currently recommended as the therapy of choice for the treatment and prevention of several arrhythmias. It can also be used to prevent its deficit, when such deficit is pathological or associated to the ingestion or certain drugs. Given the multiple properties of magnesium, controlled studies are required in order to define its potential therapeutical applications. PMID- 1504209 TI - [Diagnostic and therapeutic attitude toward a patient with a suspected urinary infection]. PMID- 1504210 TI - [Vertebral osteomyelitis caused by group B streptococci (Streptococcus agalactiae) in a previously healthy adult]. PMID- 1504211 TI - [Adult Still's disease: an unusual form of presentation]. PMID- 1504212 TI - [Neuroleptic malignant syndrome]. PMID- 1504213 TI - [Hemolytic anemia and acute renal failure caused by rifampicin]. PMID- 1504215 TI - [Rhabdomyolysis as a form of presentation of polymyositis]. PMID- 1504214 TI - ["Pseudo-osteoblastic" pattern and bone marrow metastasis as a presenting form in gastric cancer]. PMID- 1504216 TI - [Cefuroxime axetil in the treatment of lower respiratory tract infections in patients with chronic lung diseases]. PMID- 1504217 TI - [AIDS and primary acre]. PMID- 1504218 TI - [The university and primary care. The current status of the question]. PMID- 1504219 TI - [The motives for consultation and the clinical stages of HIV-positive patients attending a health center]. AB - OBJECTIVE: To find the clinical condition and motives for consultation of HIV + patients seen in our Health Centre. DESIGN: This was an observational and retrospective study. SITE. The study was carried out in the Primary Care context, in the Natahoyo Health Centre (Gijon). PATIENTS AND OTHERS PARTICIPANTS: The clinical histories of 26 HIV + patients registered at the Health Centre were studied. These supposed a total of 387 consultations from the day they were diagnosed as seropositive to the 31 August, 1991, or until their death. MAIN MEASUREMENTS AND RESULTS: The 387 consultations recorded broke down into a average of 14.8 consultations per patient (SD 12.7). 43% due to a request for detoxification. Only 5.5% of patients were referred to the second level. In line with the classifications of the W.H.O., 14 patients (56%) would be in stage I; 3 (12%) in stage II; 3 (12%) in stage III; and 5 (20%) in stage IV. CONCLUSIONS: HIV + patients often attend our Health Centre, but mainly for bureaucratic reasons. Consultations due to illness tend to be for minor pathologies, which are almost always treated successfully in the Centre itself. The WHO's classifications were found to be useful for assessing the stage of each HIV + patient at the Primary Care level. PMID- 1504220 TI - [Urinary infections. Outpatient antibiotic sensitivity in the province of Girona]. AB - OBJECTIVE: To discover the level of autochthonous urinary microflora and their sensitivity to antimicrobials, at the primary care level. DESIGN: A descriptive and retrospective study of a sequential sampling of urine cultures in primary care (during July, August and September, 1991). SITE. Primary care in the Province of Girona. PATIENTS AND OTHER PARTICIPANTS: 700 individuals between one month and 91 years, with positive urine cultures. 19% men, 68% women, 13% not specified. MAIN MEASUREMENTS AND RESULTS: 76% of the urine cultures studied contained E. coli. The proportion of Proteus and Pseudomonas is higher in the pediatric group. We detected a low sensitivity in those with urinary pathologies to ampicillin and cotrimoxazole; lower sensitivity to pipemidic acid with regards to norfloxacin; and high sensitivity to first--and second-generation cephalosporins. CONCLUSIONS: Only the knowledge of the sensitivity of pathogenic germs to antimicrobials in a specific medium can allow us to use antibiotics rationally. Knowledge can be increased by working out prospective diagnostic and treatment procedures, which could substantially improve the delivery of primary care medicines. PMID- 1504221 TI - [The conduct stemming from the application of a program of preventive activities]. AB - OBJECTIVE: To evaluate the results of putting into practice the Programme of Preventive Measures and Health Promotion of the SEMFYC and the level of intervention into each risk factor. DESIGN: Descriptive study of a sample of clinical records of patients included in the program. SITE. The population seen at a Health Centre. PATIENTS: A sample of 772 clinical records, 51.1% being women. Average age was 31.8. MAIN MEASUREMENTS AND RESULTS: 389 smokers, 35 people with hypertension, 175 with hypercholesterolemia, 96 heavy drinkers and 268 suffering from overweight were found. The level of intervention recorded in the clinical histories is low by the criteria of the Programme: it swings between 27.68% for overweight and 47.6% for tobacco dependency. CONCLUSIONS: The Programme of Preventive Measures and Health Promotion (PAPPS in Spanish) is seen to be useful as a method of detecting health problems in the asymptomatic population. But it needs to be followed up with some minimal intervention and control of the problem, if the desired aims are to be met. PMID- 1504223 TI - [Chronic patients confined to home and their impact on the family: a qualitative study]. AB - OBJECTIVE: To describe and assess the social and psychic overload which falls on those who care for chronically ill patients confined to their homes. DESIGN: Qualitative study, with semi-structured interviews. SITE: Primary care in the public sector, in an urban context. PATIENTS OR OTHERS PARTICIPANTS: Those caring for the chronically ill, confined to their homes, and who are included in the home care programme of a General Medicine office. INTERVENTION: Semi-structured interview and analysis of the clinical history. Data were obtained concerning: 1. The general characteristics of the patient; 2. General characteristics of the carer; and 3. Social activities, family relationships and both physical and psychological health of the carers. MAIN RESULTS: 12 patients were studied. Two of these had no carer. In the remaining ten cases, the carer was a member of the immediate family. Only one carer was male. In 60% of cases the carer showed dysfunction in relation to the family. There were social repercussions in 70% of the cases and psychiatric morbidity in 50%. CONCLUSION: Care of the chronically ill patient confined to the home carries with it a serious social and psychological burden, which falls essentially on the wife or daughter. PMID- 1504222 TI - [Inequality before death: a comparative study between Navarra communities in the population segment from 25 to 74 years old]. AB - OBJECTIVE: To identify differences in mortality between communities in function of certain socio-economic factors. Firstly, between the urban and rural population of Navarra; and secondly, among different neighbourhoods in Pamplona categorised according to their socioeconomic status. DESIGN: Descriptive study. As the instrument of comparison, the standard mortality rates (SMR) have been used with the direct method. The relationship between mortality and socio economic status in the neighbourhoods of Pamplona has been analysed by means of lineal regression. SITE. Institute of Public Health of Navarra. PATIENTS OR OTHERS PARTICIPANTS: Those people recorded on the Municipal Censuses of Navarra in 1986, who were between 25 and 74 years old. 8,086 of these died during our period of study, which covered the five years between 1985 and 1989. MAIN MEASUREMENTS AND RESULTS: The SMRs for all causes in men (741 x 10(6)) and women (324 x 10(6)) who live in rural communities are significantly lower (p less than 0.05) than those in urban communities (863 and 390). The specific cause of death which marks the most difference between the two types of community are tumours (p less than 0.05). In the capital (Pamplona), masculine mortality was found to increase in line with the socio-economic status of the neighbourhood lived in (p = 0.017). CONCLUSIONS: There is greater mortality in urban than in rural communities; and in neighbourhoods with low socio-economic status as against those with a high status. However, in this second case, the greater mortality only applies to men. PMID- 1504224 TI - [The demand for care at a health center according to the regional information system]. AB - OBJECTIVE: Our work is designed to find the level of demand for care in a health centre by studying data gathered with the system of regional information. DESIGN: This was a descriptive analysis of the health problems for which patients sought treatment, based on a sampling of these problems one week a month. SITE. The study, covering the whole of 1990, was carried out in an urban health centre in Valladolid. MAIN MEASUREMENTS AND RESULTS: 4.1 problems per person per year were recorded. Infants under a year old constitute the category with most problems (14.3 problems per year), followed by people over 65 (13 problems per year). The biggest group of problems concerned respiratory functions and social and administrative problems. CONCLUSIONS: In spite of the differences in methodology, there are a large number of similarities between several studies. PMID- 1504225 TI - [Vaginitis. Its diagnosis and treatment]. PMID- 1504226 TI - [Death in the family]. PMID- 1504227 TI - [Rheumatic diseases in the community]. PMID- 1504228 TI - [An analysis of the process of diagnostic and/or therapeutic support in primary care]. PMID- 1504229 TI - [Kawasaki's syndrome: the importance of an early diagnosis]. PMID- 1504230 TI - [The Reynolds syndrome. Its diagnostic accessibility and therapeutic intervention in primary care]. PMID- 1504231 TI - [The vaccinal status against tetanus in the basic health area of rural east Avila]. PMID- 1504232 TI - [Chorioretinitis due to Toxoplasma in an immunocompetent patient]. PMID- 1504233 TI - [Acute icteric hepatitis due to infectious mononucleosis]. PMID- 1504234 TI - Sleep classification in infants based on artificial neural networks. AB - The study reports on the possibility of classifying sleep stages in infants using an artificial neural network. The polygraphic data from 4 babies aged 6 weeks, 6 months and 1 year recorded over 8 hours were available for classification. From each baby 22 signals were recorded, digitized and stored on an optical disc. Subsets of these signals and additional calculated parameters were used to obtain data vectors, each of which represents an interval of 30 sec. For classification, two types of neural networks were used, a Multilayer Perceptron and a Learning Vector Quantizer. The teaching input for both networks was provided by a human expert. For the 6 sleep classes in babies aged 6 months, a 65% to 80% rate of correct classification (4 babies) was obtained for the testing data not previously seen. PMID- 1504235 TI - [Movement correction of digital sequence angiographies of the retina]. AB - Retinal hemodynamics can be quantified from videoangiographic image sequences by digital image processing. Intensity changes of dye dilution curves provide dynamics parameters of the local retinal blood flow. The measuring points of dye dilution curves have to be fixed on identical image contents in each image of a complete image sequence. To obtain measurements for every pixel on the retinal surface a motion-compensated image sequence is required. A new method adapted to the compensation of eye motion and movement artifacts in Scanning Laser Ophthalmoscopy in long image sequences (300-500 images) is presented in this paper. To inhibit error propagation of time sequential motion estimation, the eye movement is divided into two dynamic movements components. The method presented permits compensation for eye motion in retinal fluorescein angiographic sequences. Owing to the short calculation times, this algorithm can be used in clinical routine. PMID- 1504236 TI - [Online control of evaluation algorithms of the image applied to identification of deglutition function]. AB - Comprehensive software and hardware have been developed for the processing of biosignals. Such automatic signal processing, however not only has advantages, but also drawbacks. The question as to the reliability of the evaluation algorithm arises when the signal is modified, in the presence of interindividual differences, and in particular when noise is superimposed. This is of great interest for long-term recording when the original signal can no longer be inspected visually. The aim of our work was to display the signals on the screen of a monitor simultaneously with lines marking the points (start, end, extreme value, etc.) processed by the specific signal processing algorithm. The program package permits the on-line recording and monitoring of signals, the parallel processing and marking of detected events on the monitor, as well as storage of the parameters extracted. It is a very effective tool for developing, improving and monitoring of algorithms and their efficiency for signal processing. PMID- 1504237 TI - Calorimetric studies on the influence of N-methylated headgroups on the mixing behavior of diheptadecanoyl phosphatidylcholine with 1-behenoyl-2 lauroylphosphatidylcholine. AB - Recent studies of five different phosphatidylcholine/phosphatidylcholine (PC/PC) systems indicate that binary mixtures of phosphatidylcholines in which one component has a normalized chain length difference (delta C/CL) in the range of 0.09-0.40 and the other a delta C/CL in the range of 0.42-0.57 exhibit the phase behavior of a eutectic system. Here, delta C is the effective chain-length difference between the two acyl chains, and CL is the effective length of the longer of the two acyl chains for the same lipid molecule in the gel state. In each mixture, gel phase immiscibility occurs over a wide compositional range due to the difference in the gel phase acyl chain packing properties of each component. Although the mixtures differ in the location of their eutectic horizontal, with respect to temperature, all have a similar eutectic point that occurs at a composition of approximately 40 mol percent of the component with the delta C/CL value in the range of 0.42-0.57. Here, we extend these studies by systematically modifying the headgroup of C(17):C(17)PC and then analyzing the mixing behavior of the modified lipid with C(22):C(12)PC using DSC. Progressive demethylation of the C(17):C(17)PC headgroup leads to an increase in gel phase immiscibility and a decrease in the amount of C(22):C(12)PC that comprises the eutectic composition. The temperature defining the location of the eutectic horizontal, however, remains virtually unchanged in all three phase diagrams. Our results suggest that the eutectic composition is influenced by changes in gel phase acyl chain packing that are dependent on headgroup-headgroup interactions. In contrast, the eutectic nature of the phase diagram and the location of its solidus line are properties of acyl chain interactions that are independent of phospholipid headgroup-headgroup interactions. PMID- 1504238 TI - Monovalent cation binding to cubic insulin crystals. AB - Two localized monovalent cation binding sites have been identified in cubic insulin from 2.8 A-resolution difference electron density maps comparing crystals in which the Na+ ions have been replaced by Tl+. One cation is buried in a closed cavity between insulin dimers and is stabilized by interaction with protein carbonyl dipoles in two juxtaposed alternate positions related by the crystal dyad. The second cation binding site, which also involves ligation with carbonyl dipoles, is competitively occupied by one position of two alternate His B10 side chain conformations. The cation occupancy in both sites depends on the net charge on the protein which was varied by equilibrating crystals in the pH range 7-10. Detailed structures of the cation binding sites were inferred from the refined 2 A resolution map of the sodium-insulin crystal at pH 9. At pH 9, the localized monovalent cations account for less than one of the three to four positive counterion charges necessary to neutralize the negative charge on each protein molecule. The majority of the monovalent counterions are too mobile to show up in the electron density maps calculated using data only at resolution higher than 10 A. Monovalent cations of ionic radius less than 1.5 A are required for crystal stability. Replacing Na+ with Cs+, Mg++, Ca++ or La+++ disrupts the lattice order, but crystals at pH 9 with 0.1 M Li+, K+, NH4+, Rb+ or Tl+ diffract to at least 2.8 A resolution. PMID- 1504239 TI - Microviscosity of human erythrocytes studied using hypophosphite two-spin order relaxation. AB - A new 31P NMR method is used to probe the cytoplasmic viscosity of human erythrocytes. The method is based on observing two-spin order relaxation of the 31P atom of the hypophosphite ion. This method is superior to our previous method, using the longitudinal relaxation time of the ion, because random field effects such as intermolecular dipole-dipole relaxation can be separated from intramolecular relaxation. This allows a more accurate determination of the effective reorientational correlation time from the measured intramolecular relaxation because it is now unaffected by random field effects. The new method also provides a means by which to estimate the random field effects. Both two spin order and proton-decoupled T1 measurements were conducted on hypophosphite in water solutions at various temperatures, glycerol solutions of various viscosities, and in erythrocyte samples of various cell volumes. The results show that the effective reorientational correlation time of the hypophosphite ion varies from 7.2 to 15.2 ps in the cytoplasm of cells ranging in volume from 102 to 56 fl cells. PMID- 1504240 TI - Ion effects on gating of the Ca(2+)-activated K+ channel correlate with occupancy of the pore. AB - We studied the effects of permeant ions on the gating of the large conductance Ca(2+)-activated K+ channel from rat skeletal muscle. Rb+ blockade of inward K+ current caused an increase in the open probability as though Rb+ occupancy of the pore interferes with channel closing. In support of this hypothesis, we directly measured the occupancy of the pore by the impermeant ion Cs+ and found that it strongly correlates with its effect on gating. This is consistent with the "foot in-the-door" model of gating, which states that channels cannot close with an ion in the pore. However, because Rb+ and Cs+ not only slow the closing rate (as predicted by the model), but also speed the opening rate, our results are more consistent with a modified version of the model in which the channel can indeed close while occupied, but the occupancy destabilizes the closed state. Increasing the occupancy of the pore by the addition of other permeant (K+ and Tl+) and impermeant (tetraethylammonium) ions did not affect the open probability. To account for this disparity, we used a two-site permeation model in which only one of the sites influenced gating. Occupancy of this "gating site" interferes with channel closing and hastens opening. Ions that directly or indirectly increase the occupancy of this site will increase the open probability. PMID- 1504241 TI - Dynamics of energy transfer and trapping in the light-harvesting antenna of Rhodopseudomonas viridis. AB - By low intensity picosecond absorption spectroscopy it is shown that the exciton lifetime in the light-harvesting antenna of Rhodopseudomonas (Rps.) viridis membranes with photochemically active reaction centers at room temperature is 60 +/- 10 ps. This lifetime reflects the overall trapping rate of the excitation energy by the reaction center. With photochemically inactive reaction centers, in the presence of P+, the exciton lifetime increases to 150 +/- 15 ps. Prereducing the secondary electron acceptor QA does not prevent primary charge separation, but slows it down from 60 to 90 +/- 10 ps. Picosecond kinetics measured at 77 K with inactive reaction centers indicates that the light-harvesting antenna is spectrally homogeneous. Picosecond absorption anisotropy measurements show that energy transfer between identical Bchlb molecules occurs on the subpicosecond time scale. Using these experimental results as input to a random-walk model, results in strict requirements for the antenna-RC coupling. The model analysis prescribes fast trapping (approximately 1 ps) and an approximately 0.5 escape probability from the reaction center, which requires a more tightly coupled RC and antenna, as compared with the Bchla-containing bacteria Rhodospirillum (R.) rubrum and Rhodobacter (Rb.) sphaeroides. PMID- 1504242 TI - Significance of glomerular compartmentalization for olfactory coding. AB - This paper deals with the dendritic signal processing by mitral cells in the olfactory bulb and its meaning for olfactory coding. The output signals of olfactory receptor neurones are sent to the olfactory bulb where they converge onto the secondary neurones, the mitral cells. On a short time scale, the connectivity between receptor and mitral cells can be assumed to be constant, whereas on a longer time scale, when considering the ongoing de- and regeneration, it is necessary to model the synaptical weights between receptor and mitral cells as variables. In a first approach we used Hebb's rule to this end and presumed that a mitral cell can be represented by one compartment only. In this case, and with a sequence of realistically modeled receptor activity signals, the synaptical weights of all mitral cells converged to the same point though every mitral cell had initial weights different from those of any other mitral cell. This means that a mitral cell, when modeled as one compartment, does not become sensitive to any particular odor quality. A similar lack of quality tuning turned out to occur when one-compartment mitral cells were connected among each other by laterally inhibiting interneurones. We therefore took into account the glomerular fine structure of mitral cell dendrites, assuming electrotonically decoupled dendritic subbranches. This feature together with local inhibitory circuitry at the subbranches led to a fundamentally different type of synaptical convergence pattern. In this case, mitral cells developed differential sensitivities for different odors. Mitral cells have thus to be regarded as multicompartment cells, and local, non-Hebbian learning rules for their afferent synapses are necessary to achieve a reasonable map of odors upon mitral cell activities. PMID- 1504243 TI - Spectral hole burning study of protoporphyrin IX substituted myoglobin. AB - Protoporphyrin IX substituted myoglobin reveals excellent hole burning properties. We investigated the frequency shift of persistent spectral holes under isotropic pressure conditions in a range from 0 to 2.4 MPa. In this range, the protein behaves like an elastic solid. The shift of the holes under pressure shows a remarkable frequency dependence from which the compressibility of the protein can be determined. The compressibility, in turn, allows for an estimation of the equilibrium volume fluctuations. Within the frame of the model used to interpret the pressure data, it is possible to determine the absorption frequency of the isolated chromophore and the associated solvent shift in the protein environment. PMID- 1504244 TI - Structural polymorphism correlated to surface charge in filamentous bacteriophages. AB - Fiber diffraction studies are used to demonstrate that changes in the helical symmetry of the protein coat of filamentous bacterial viruses fd and M13 are correlated with changes in the surface charge. Comparison of the structure of M13 and fd at pH 2 and 8 indicate that surface charge affects both the helical symmetry and flexibility of the virions. The changes in helical symmetry are similar in magnitude to that observed in the Pseudomanas phage Pf1 and probably reflect an inocuous side effect of the particle flexibility required for protection of the virus particles from damage due to shear. The magnitude of the observed changes in helical symmetry appears to be limited to that which can occur without repacking of the interfaces between the alpha-helices making up the viral protein coat. PMID- 1504245 TI - Multiple conductances in the large K+ channel from Chara corallina shown by a transient analysis method. AB - The large conductance K+ channel in the tonoplast of Chara corallina has subconductance states (substates). We describe a method that detects substates by monitoring the time derivative of channel current. Substates near to the full conductance tend to have long durations and high probabilities, while those of smaller amplitude occur with less probability and short duration. The substate pattern is similar in cell-attached, inside-out and outside-out patches over a range of temperatures. The pattern changes at high Ca2+ concentration (10 mol m 3) on the cytoplasmic face of inside-out patches. One substate at approximately 50% of the full conductance is characterized by a high frequency of transitions from the full conductance level. This midstate conductance is not a constant proportion of the full conductance but changes as a function of membrane potential difference (p.d.) showing strong inward rectification. We suggest that the channel is a single pore that can change conformation and/or charge profile to give different conductances. The mean durations of the full conductance level and the midstate decrease as the membrane p.d. becomes more negative. Programs for analysis of channel kinetics based on an half-amplitude detection criterion are shown to be unsuitable for analysis of the K+ channel. PMID- 1504246 TI - Cable analysis with the whole-cell patch clamp. Theory and experiment. AB - A theoretical analysis was undertaken of a Rall motoneuron under voltage clamp with a finite access resistance. This model is relevant to the conditions of the whole-cell patch clamp, which to date has been used very little for cable analysis. It was shown that the soma and cable charging currents can be distinguished, and that the soma is charged with a time constant approximately equal to the access resistance times the somatic capacitance. Thus, the charging time of the soma is similar to what it would be if the cell had no process. Simple formulas were derived that can be used to calculate the electrotonic length, the membrane time constant, and the soma-dendrite resistance ratio of a cell with a cylindrical process. With the aid of these formulas, reasonable estimates of parameter values were recovered from simulated transient currents. Tests of the Rall model were proposed to determine when there is an equivalent cylinder that is consistent with observed charging behavior. The analysis was extended to a cable with an open end and to a model in which the soma and dendrite have different membrane time constants. It was shown that with voltage clamp data estimates of electrical parameters other than rho are relatively insensitive to differences between the membrane properties of the soma and dendrite. The methods of cable analysis introduced here were illustrated by application to charging transients recorded from a hippocampal pyramidal cell and from a neurohypophysial nerve ending. The Rall model provided a good description of the pyramidal cell current transient but was inconsistent with the charging behavior observed for the nerve ending. With the recent technical advance of patch clamp recording in brain slices, the analysis presented here should help neurophysiologists investigate cable properties in a wide variety of systems. PMID- 1504247 TI - Comparison of the lipid acyl chain dynamics between small and large unilamellar vesicles. AB - 13C NMR spin-lattice relaxation (T1) rates and 13C-1H nuclear Overhauser effects (NOEs) were measured in an identical fashion in two lipid preparations having dramatically different curvatures. The T1 times that were obtained at four magnetic field strengths were fit along with the NOEs to simple models for lipid molecular dynamics. The results indicate that phospholipid chain ordering and dynamics are virtually identical in small and large unilamellar vesicles at the time scales sampled by these 13C-NMR studies. The order parameters and reorientational correlation times that characterize the amplitudes and rates of internal acyl chain motions were equal within experimental error for the methylene segments in the middle of the chains. The only significant differences in order parameters and correlation times between the two vesicle types were small and appeared at the ends of the acyl chains. At the carbonyl end the order was slightly higher in small vesicles than large vesicles, and at the methyl end the order was slightly lower for small vesicles. This indicates that in the more planar systems the acyl chains exhibit a slightly flatter order profile than in more highly curved membranes. The use of the same experimental approach in both small and large vesicle systems provided a more reliable and accurate assessment of the effect of curvature on molecular order than has been previously obtained. PMID- 1504248 TI - Intermolecular protein interactions in solutions of calf lens alpha-crystallin. Results from 1/T1 nuclear magnetic relaxation dispersion profiles. AB - From analyses of the magnetic field dependence of 1/T1 (NMRD profiles) of water protons in solutions of calf lens alpha-crystallin at several concentrations, we find two regimes of solute behavior in both cortical and nuclear preparations. Below approximately 15% vol/vol protein concentration, the solute molecules appear as compact globular proteins of approximately 1,350 (cortical) and approximately 1,700 (nuclear) kD. At higher concentrations, the effective solute particle size increases, reversibly, as evidenced by the appearance of spectra like 14N peaks in the NMRD profiles and a change in the field and temperature dependence of 1/T1. At these higher concentrations, the profiles are very similar to those of calf gamma II-crystallin, a crystallin that undergoes an analogous transition near approximately 15% protein (Koenig, S. H., C.F. Beaulieu, R. D. Brown III, and M. Spiller, 1990. Biophys. J. 57:461-469). By comparison with recent analyses of NMRD results for solutions of immobilized proteins as models for the transition from protein solutions to tissue (Koenig, S. H., and R. D. Brown III. 1991. Prog. NMR Spectr. 22:487-567), we argue that alpha-crystallin solute behaves as aggregates approximately greater than 50,000 kD as protein concentration is progressively increased above 15%. Finally, the concentration dependence of the NMRD profiles of alpha- and gamma II-crystallin can readily explain recent osmotic pressure data, in particular the intersection of the respective pressure curves at approximately 23% vol/vol (Veretout, F., and A. Tardieu. 1989. Eur. Biophys. J. 17:61-68). PMID- 1504249 TI - Modulation of the interbilayer hydration pressure by the addition of dipoles at the hydrocarbon/water interface. AB - The effects of the cholesterol analog 5 alpha-cholestan-3 beta-ol-6-one (6 ketocholestanol) on bilayer structure, bilayer cohesive properties, and interbilayer repulsive pressures have been studied by a combination of x-ray diffraction, pipette aspiration, and dipole potential experiments. It is found that 6-ketocholestanol, which has a similar structure to cholesterol except with a keto moiety at the 6 position of the B ring, has quite different effects than cholesterol on bilayer organization and cohesive properties. Unlike cholesterol, 6-ketocholestanol does not appreciably modify the thickness of liquid-crystalline egg phosphatidylcholine (EPC) bilayers, and causes a much smaller increase in bilayer compressibility modulus than does cholesterol. These data imply that 6 ketocholestanol has both its hydroxyl and keto moieties situated near the water hydrocarbon interface, thus making its orientation in the bilayer different from cholesterol's. The addition of equimolar 6-ketocholestanol into EPC bilayers increases the magnitude, but not the decay length, of the exponentially decaying repulsive hydration pressure between adjacent bilayers. Incorporation of equimolar 6-ketocholestanol into EPC monolayers increases the dipole potential by approximately 300 mV. These data are consistent with our previous observation that the magnitude of the hydration pressure is proportional to the square of the dipole potential. These results mean that 6-ketocholestanol, despite its location in the bilayer hydrocarbon region, approximately 10 A from the physical edge of the bilayer, modifies the organization of interlamellar water. We argue that the incorporation of 6-ketocholestanol into EPC bilayers increases the hydration pressure, at least in part, by increasing the electric field strength in the polar head group region. PMID- 1504250 TI - Events leading to the opening and closing of the exocytotic fusion pore have markedly different temperature dependencies. Kinetic analysis of single fusion events in patch-clamped mouse mast cells. AB - The earliest event in exocytosis is the formation of a fusion pore, an aqueous channel that connects the lumen of a secretory granule with the extracellular space. We can observe the formation of individual fusion pores and their subsequent dilation or closure by measuring the changes in the admittance of patch-clamped mast cells during GTP gamma S-stimulated exocytotic fusion. To investigate the molecular structure of the fusion pore, we have studied the temperature dependency of the rate constants for fusion pore formation and closure. An Arrhenius plot of the rate of fusion pore formation shows a simple linear relationship with an apparent activation energy of 23 kcal/mol. In contrast, the Arrhenius plot of the rate of closure of the fusion pore is discontinuous, with the break at approximately 13 degrees C. Above the break point, the rate of closure has a weak temperature dependence (7 kcal/mol), whereas below 13 degrees C the rate of closure is temperature independent. This type of temperature dependency is characteristic of events that depend on diffusion in a lipid phase that undergoes a fluid-solid phase transition. We propose that the formation of the fusion pore is regulated by the conformational change of a molecular structure with a high activation energy, whereas the closure of the fusion pore is regulated by lipids that become phase separated at 13 degrees C. PMID- 1504251 TI - Determination of electric field threshold for electrofusion of erythrocyte ghosts. Comparison of pulse-first and contact-first protocols. AB - Rabbit erythrocyte ghosts were fused by means of electric pulses to determine the electrofusion thresholds for these membranes. Two protocols were used to investigate fusion events: contact-first, and pulse-first. Electrical capacitance discharge (CD) pulses were used to induce fusion. Plots of fusion yield vs peak field strength yielded curves that intersected the field strength axis at positive values (pseudothresholds) which depended on the protocol and decay half time of the pulses. It was found that plots of pseudothreshold vs reciprocal half time were linear for each protocol; when extrapolated to reciprocal half time = 0 (i.e., t----infinity), these lines intersected the ordinate at values of the field strength considered to be the true electrofusion thresholds. In this fashion, the contact-first protocol gave an electrofusion threshold of 46.5 +/- 11.5 V/mm for hemoglobin-free ghosts (white ghosts) and 40.9 +/- 8.8 V/mm for ghosts with fractional hemoglobin (pink ghosts), while the threshold for the pulse-first protocol applied to pink ghosts was determined to be 93.4 +/- 11.0 V/mm. Although the thresholds depended on the electrofusion protocol, plots of critical field strength vs reciprocal time had the same slopes, i.e., approximately 24 Vs/mm. The results suggest that the fusogenic state induced by an electric pulse in either the contact-first protocol or the pulse-first protocol (long-lived fusogenic state) may in fact share a common mechanism, if the two states are not actually identical. PMID- 1504252 TI - Flexibility in crystalline insulins. AB - Comparisons of atomic models for chemically identical protein molecules solved in differing crystal environments provide information on flexibility in the protein structure. The structures of five T4 lysozyme proteins in differing crystal environments showed large relative displacements of the two domains with conserved backbone conformations that are connected by a flexible hinge (H. R. Faber and B. W. Matthews. 1990. Nature (Lond.). 348:263-266). In contrast, my comparison of the positions of all the atoms in two crystal forms of insulin shows that the structural changes caused by the differing crystal contacts are contained within nearby amino acids and are not propagated through the core of the insulin molecule. Groups of atoms that are most significantly displaced are not shifted in large rigid units but are repacked into new and distinct conformations. The transmission of displacements through the single domain insulin molecule is, like the movements due to thermal vibrations (D. L. D. Caspar, J. Clarage, D. M. Salunke, M. S. Clarage. 1988. Nature (Lond.). 332:659 662), characterized by short-range interactions between small atomic groups. PMID- 1504254 TI - The endo-8,9-epoxide of aflatoxin B1: a new metabolite. PMID- 1504253 TI - A residue substitution near the beta-ionone ring of the retinal affects the M substates of bacteriorhodopsin. AB - The switch in the bacteriorhodopsin photocycle, which reorients access of the retinal Schiff base from the extracellular to the cytoplasmic side, was suggested to be an M1----M2 reaction (Varo and Lanyi. 1991. Biochemistry. 30:5008-5015, 5016-5022). Thus, in this light-driven proton pump it is the interconversion of proposed M substates that gives direction to the transport. We find that in monomeric, although not purple membrane-lattice immobilized, D115N bacteriorhodopsin, the absorption maximum of M changes during the photocycle: in the time domain between its rise and decay it shifts 15 nm to the blue relative to the spectrum at earlier times. This large shift strongly supports the existence of two M substates. Since D115 is located near the beta-ionone ring of the retinal, the result raises questions about the possible involvement of the retinal chain or protein residues as far away as 10 A from the Schiff base in the mechanism of the switching reaction. PMID- 1504255 TI - Supercritical fluid extraction in the determination of tobacco-specific N nitrosamines in smokeless tobacco. AB - A new approach to the analysis of the carcinogenic, tobacco-specific N nitrosamines (TSNA) in moist snuff tobacco is based on the extraction of tobacco with methanol-modified supercritical carbon dioxide. Extracted TSNA are trapped across a glass cartridge filled with Tenax GR, from which they are subsequently released by thermal desorption and analyzed by capillary gas chromatography with a thermal energy analyzer. The analytical recoveries for the major TSNA range from 83 to 98%; the detection limits are below 2 ng/g. The methodology is fast, reproducible, highly selective, and sensitive. The supercritical fluid extraction (SFE) releases up to 7 times more of the highly carcinogenic 4 (methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) from tobacco than has been determined after conventional solvent extraction. Studies have confirmed that this is not an artifact. In contrast, the cyclic N-nitrosamines, N' nitrosonornicotine, N'-nitrosoanabasine, and N'-nitrosoanatabine, showed no significant quantitative differences whether determined by the SFE method or the conventional solvent extraction method. PMID- 1504256 TI - The oxidation of 4-aminobiphenyl by horseradish peroxidase. AB - The oxidation of the carcinogen 4-aminobiphenyl (4-ABP) catalyzed by the model peroxidase enzyme horseradish peroxidase (HRP) was investigated. 4-ABP served as a reducing cosubstrate for HRP during the enzyme-catalyzed reduction of the synthetic hydroperoxide, 5-phenyl-4-penten-1-yl hydroperoxide, to its corresponding alcohol. Spectral analysis during the incubation of HRP, 4-ABP, and H2O2 showed an increase in absorbance at 230 and 325 nm and decrease at 270 nm, suggesting metabolite formation. Oxygen consumption was not detected in incubations of HRP, 4-ABP, and H2O2. However, oxygen uptake was observed after the addition of glutathione, which indicated that a free radical metabolite of 4 ABP was formed by the peroxidase. The 4-ABP free radical reacted with glutathione forming a glutathionyl radical which, in turn, reacted with and consumed oxygen. HPLC analysis of organic extracts of incubations with HRP, [3H]-4-ABP, and H2O2 showed the formation of one major peak identified by mass spectroscopy as 4,4' azobis(biphenyl). The addition of glutathione to the incubations decreased the formation of 4-ABP metabolites, suggesting a reduction of the 4-ABP free radical and/or the formation of glutathione conjugates. Subsequent HPLC analysis of incubations including [35S]glutathione indicated formation of several unidentified 4-ABP-glutathione conjugates as well as recovery of parent compound. These studies suggest that HRP metabolizes 4-ABP by a one-electron oxidation mechanism, resulting in formation of a free radical. This radical can either react with a second radical to form azobis(biphenyl), be reduced by glutathione back to parent, or react with glutathione to form glutathione conjugates. PMID- 1504257 TI - Correlation studies of anodic peak potentials and ionization potentials for polycyclic aromatic hydrocarbons. AB - One-electron oxidation represents one of the major metabolic pathways of bioactivation of polycyclic aromatic hydrocarbons (PAH) to ultimate carcinogens capable of binding to cellular macromolecules, thereby initiating the cancer process. Since the ionization potential (IP) is related to the ease of removal of a pi electron from an aromatic molecule, a low IP is a necessary condition for the PAH to undergo one-electron oxidation. The principal aim of this study was to provide a general and simple technique suitable for obtaining IP of PAH with satisfactory accuracy. Anodic peak potentials (Eap) of 90 PAH were measured by cyclic voltammetry under irreversible oxidation conditions and correlated with the corresponding IP. This allowed determination of a least-squares regression line. From the corresponding equation, IP = 1.70Eap + 5.29, IP can be calculated with a narrow margin of error after a simple electrochemical measure. It was also found that PAH substituted with a methyl group on a position of appreciable electron density are best represented by a different line, corresponding to the equation IP = 1.65Eap + 5.27. The calculated IP were also compared to other tabulated values, determined by different experimental techniques, and our set of IP values proved to yield the most satisfactory correlation. For some PAH, further studies under reversible voltammetric conditions allowed determination of two additional parameters: formal oxidation potentials (Eo) and the number of electrons (n) involved in the redox process. IP is an important parameter in predicting the metabolic activation of carcinogenic PAH. PMID- 1504258 TI - Antioxidant activity of the pyridoindole stobadine. Pulse radiolytic characterization of one-electron-oxidized stobadine and quenching of singlet molecular oxygen. AB - Antioxidant properties of stobadine, a pyridoindole derivative described to exhibit cardioprotective properties, were characterized. The radical scavenging potential of stobadine was evaluated using pulse radiolysis with optical detection, by which it is shown that one-electron oxidation of stobadine with radicals such as C6H5O., CCl3O2., Br2.-, and HO. (reaction rate constants approximately 5 x 10(8)-10(10) M-1 s-1) leads to the radical cation (absorbance maxima at 280 and 445 nm) which deprotonates from the indolic nitrogen (pKa = 5.0) to give a nitrogen-centered radical (absorbance maxima at 275, 335, and 410 nm), probably bearing a positive charge at the pyrido nitrogen. The radical of stobadine reacts with Trolox (i.e., 6-hydroxy-2,5,7,8-tetramethyl-chromane-2 carboxylic acid) with a rate constant of 1.2 x 10(7) M-1 s-1 at pH 7.0 by one electron oxidation to yield the phenoxyl-type radical of Trolox. This reaction is reversible (k = 2 x 10(5) M-1 s-1). The redox potential of stobadine at pH 7 is 0.58 V/NHE. Stobadine is also a quencher of singlet molecular oxygen (1O2) with an overall quenching rate constant of 1.3 x 10(8) M-1 s-1, determined with the endoperoxide of 3,3'-(1,4-naphthylene)dipropionate (NDPO2) as 1O2 source and by monitoring 1O2 photoemission with a germanium diode. PMID- 1504259 TI - Bioactivation mechanism of S-(3-oxopropyl)-N-acetyl-L-cysteine, the mercapturic acid of acrolein. AB - S-(3-Oxopropyl)glutathione, the glutathione conjugate of acrolein, has been reported to be nephrotoxic. The objective of the present studies was to investigate the bioactivation mechanism of the analogues S-(3-oxopropyl)-N-acetyl L-cysteine (1) and S-(3-oxopropyl)-N-acetyl-L-cysteine S-oxide (2) and to test the hypothesis that the cytotoxicity of 1 is associated with its latent potential to release acrolein in kidney cells. Mechanistic considerations indicated that sulfoxidation of sulfide 1 to form S-oxide 2 and a subsequent general-base catalyzed beta-elimination reaction would release the cytotoxin acrolein. Hence the release of acrolein from 1 and 2 was studied in chemical systems, and their cytotoxicity was investigated in cultured LLC-PK1 cells and in isolated rat renal proximal tubular cells. Acrolein formation from S-oxide 2, but not from sulfide 1, was observed under basic conditions and with phosphate as the base. Kinetic analysis indicated that a general-base-catalyzed reaction was involved. Both S conjugates 1 and 2 were cytotoxic in LLC-PK1 cells and in isolated rat renal proximal tubular cells, and the cytotoxicity of sulfide 1, but not of S-oxide 2, in isolated renal proximal tubular cells was reduced in presence of methimazole, an inhibitor of the flavin-containing monooxygenase. These findings indicate that the cytotoxicity of S-conjugate 1 is associated with a novel bioactivation mechanism that involves sulfoxidation followed by a general-base-catalyzed elimination of acrolein from S-oxide 2. PMID- 1504260 TI - Quantitative structure-metabolism relationship analyses of MAO-mediated toxication of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine and analogues. AB - The 1-octanol/water partition coefficients of a number of toxic and nontoxic analogues of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) were determined using centrifugal partition chromatography (CPC), a novel and effective technique for measuring lipophilicity, and found to be highly correlated with values calculated by a fragmental method. Some conformational properties of these compounds were also assessed by molecular mechanics calculations and 1H-NMR spectroscopy. A quantitative structure-metabolism relationship (QSMR) study of MPTP and analogues based on literature data was undertaken in order to determine the key features eliciting MAO-A and MAO-B reactivity and selectivity and influencing toxication. Multiple regression analysis (MRA) and comparative molecular field analysis (CoMFA) showed that MAO-B activity is nonlinearly (parabolically or bilinearly) correlated to the lipophilicity of MPTP analogues and influenced negatively by steric effects exerted by bulky substituents in the ortho position. With regard to MAO-A activity, while lipophilicity was shown to play no relevant role, electrostatic and steric fields led to a 3D-QSAR model with an acceptable predictive value (cross-validated r2 = 0.571). The results of this study bring evidence at a quantitative level that the MAO-B and MAO-A catalytic sites differ in their hydrophobic, steric, and stereoelectronic requirements. PMID- 1504261 TI - Identification of cyclophosphamide-DNA adducts in rat embryos exposed in vitro to 4-hydroperoxycyclophosphamide. AB - Cyclophosphamide and other bifunctional alkylating agents are potent animal teratogens inducing a variety of malformations. Although cyclophosphamide-induced DNA damage is implicated as a primary mechanism underlying the teratogenesis initiated by cyclophosphamide, additional insights into the complex nature of the teratogenic process have been hampered by the inability to analyze the primary teratogenic lesions, i.e., cyclophosphamide-DNA adducts. Using tandem mass spectrometry, we show that the monofunctional adduct N-(2-chloroethyl)-N-[2-(7 guaninyl)ethyl]amine (NOR-G) and bifunctional adduct N,N-bis[2-(7 guaninyl)ethyl]amine (G-NOR-G) can be detected in the DNA of organogenesis-stage rat embryos after an in vitro exposure to an embryotoxic concentration of activated cyclophosphamide, i.e., 4-hydroperoxycyclophosphamide. PMID- 1504262 TI - Utilization of glutathione during 1,2-dihaloethane metabolism in rat hepatocytes. AB - The metabolism of 1,2-dihaloethanes (DHEs) to glutathione-containing metabolites by freshly isolated rat hepatocytes was investigated. 1,2-Dichloroethane (DCE), 1,2-dibromoethane (DBE), and 1-bromo-2-chloroethane (BCE) were metabolized to S (2-hydroxyethyl)glutathione (HEG), S-(carboxymethyl)glutathione (CMG), and S,S' (1,2-ethanediyl)bis(glutathione) (GEG). The formation of these glutathione containing metabolites was concomitant with the depletion of intracellular glutathione (GSH) and accounted for 58%, 84%, and 71% of the DCE-, BCE-, and DBE induced loss of intracellular GSH, respectively. The covalent binding of [14C]DBE to hepatocyte protein reached 18.7 nmol/mL of cell suspension (7.8 nmol/mg of protein) within 2.0 h of incubation. Half of this covalent binding occurred within 0.5 h of incubation (4.0 nmol/mg of protein) in the presence of high levels of intracellular GSH (30% of initial GSH level at 0.5 h). Hepatocyte metabolism of 2-chloroacetic acid produced only CMG. 2-Chloroethanol metabolism gave rise to CMG and HEG in a 11.5:1.0 ratio; 2-chloroacetaldehyde produced almost equal amounts of CMG and HEG. GEG formation was increased significantly for DBE and BCE when GSH was added to the medium during treatment, suggesting that the GSH conjugates S-(2-haloethyl)glutathione are exported from the hepatocytes. These results indicate that the glutathione S-transferase-catalyzed conjugation of GSH with the DHEs is responsible for the majority of the DHE induced GSH depletion. The S-(2-haloethyl)glutathione conjugates appear responsible for the extensive covalent binding to protein observed during [14C]DBE metabolism. PMID- 1504263 TI - Associations of the bacterial mutagenicity of halogenated 2(5H)-furanones with their MNDO-PM3 computed properties and mode of reactivity with sodium borohydride. AB - Electrophilicity as a general basis for both the mutagenicity and nucleophile inactivation of halogen-substituted 2(5H)-furanones was tested. Lowest unoccupied molecular orbital (LUMO) energy levels and stabilities of 2(5H)-furanone radical anions and C-2, C-3, and C-4 anionic hydride adducts were computed with MNDO-PM3 for each of 10 compounds. These three computed sets of values were considered electrophilicity indicators. Each individual value from a given indicator set was plotted against the logarithm of the Salmonella typhimurium (TA100) mutagenicities (log Mm) for each of the corresponding compounds. Highest occupied molecular orbital (HOMO) energy levels for the 10 compounds were also computed. Strong negative correlations were obtained from the plots of LUMO and radical anion stability against log Mm of the 10 compounds. Also, a negative correlation was observed for the plot of the stability of the C-4 anionic hydride adduct for a smaller set of six compounds possessing a 4-(chloromethyl)-2(5H)-furanone structure and having the same HOMO characteristics. HOMO energies failed to correlate with mutagenicity. Neither computed atomic charge nor 13C chemical shift values for the larger compound group of 10 correlated well with mutagenicity or with each other. Sodium borohydride and borodeuteride reductions of 3-chloro-4-(dichloromethyl)-5-hydroxy-2(5H)-furanone demonstrated experimentally that hydride became attached to C-4. PMID- 1504264 TI - The calcium-binding protein calreticulin is covalently modified in rat liver by a reactive metabolite of the inhalation anesthetic halothane. AB - A general procedure is presented for the isolation of several liver microsomal target proteins of the reactive trifluoroacetyl halide metabolite of halothane. It was found that most of these proteins could be selectively extracted from microsomes with 0.1% sodium deoxycholate and separated into partially purified fractions by DEAE-Sepharose anion-exchange chromatography. Using this method, we describe the isolation and identification of a 63-kDa target protein of halothane in rat liver. Amino acid sequences of the N-terminal and of several internal peptides of the protein, as well as the deduced amino acid sequence of a nearly full-length rat liver cDNA clone of the protein, showed 98% identity with a reported murine cDNA that encodes for calreticulin, a major calcium-binding protein of the lumen of endoplasmic reticulum. Although it remains to be determined what role calreticulin has in the development of halothane hepatitis, this study has shown that calreticulin can be a target of reactive metabolites of xenobiotics. PMID- 1504265 TI - Inhibition of acetylcholinesterase by hemicholiniums, conformationally constrained choline analogues. Evaluation of aryl and alkyl substituents. Comparisons with choline and (3-hydroxyphenyl)trimethylammonium. AB - 2-Substituted-2-hydroxy-4,4-dimethylmorpholiniums (hemicholiniums) inhibit acetylcholinesterase (EC 3.1.1.7)-catalyzed hydrolysis of acetylthiocholine (ATCh). The 4-substituted arenes [NH2, NHC(O)CH3, Cl, CN, and NO2] have values of inhibition constants (Ki) that range from 220 to 3690 microM, which correlate with Hammett sigma, rho approximately 0.8. The alkyl compounds, hydrogen, methyl, tert-butyl, and trifluoromethyl, have values of Ki of 550, 560, 1200, and 1200 microM, respectively. These values compare favorably with Ki = 960 microM for choline. The conformation of AChE-bound choline must be gauche to support our suggestion that hemicholiniums are conformationally constrained analogues of choline. (3-Hydroxyphenyl)trimethylammonium (5) inhibits most strongly, Ki = 0.21 microM, of the compounds examined in this study. The solvent isotope effect (H2OKi/D2OKi = 0.83 +/- 0.04) suggests that inhibition by 5 involves hydrogen bonding. The binding by AChE of the hemicholiniums of various sizes and the strong binding of 5 support an earlier proposal [Schowen, K. B., Smissman, E. E., and Stephen, W. F., Jr. (1975) J. Med. Chem. 18, 292-300] that the active site of AChE has ample space for rotation about the C-C bond in choline. Compound 5, which has one more carbon between the hydroxy and trimethylammonium than does choline, inhibits much more potently than either choline or the hemicholiniums. Compound 5 provides a correct spacer to span the trimethylammonium recognition site and the esteratic site of AChE. This aromatic spacer interacts favorably with the hydrophobic active site, and the phenolic hydroxyl probably hydrogen bonds to the histidine in the esteratic site. Choline in any conformation and the hemicholiniums are too short to make a strong hydrogen bond. PMID- 1504266 TI - Toxicology of drinking water disinfection byproducts from nutrients. Rate studies of destruction of polyunsaturated fatty acids in vitro by chlorine-based disinfectants. AB - As model reactions between unsaturated fats and water disinfectants in the GI tract, relative rates of destruction of seven polyunsaturated fatty acids (L, alpha Ln, gamma Ln, Ara, EPA, DH, and DT) by OCl- and NH2Cl were investigated in vitro. Using millimolar solutions of seven PUFAs combined with various OCl- mole ratios, disappearance of PUFAs was followed by UV spectrophotometry at pH = 9.5 and at 35 degrees C via conjugated hydroperoxydienes at 234 nm. While OCl- rapidly destroyed all PUFAs, NH2Cl was inert. Overall second-order rate constants computed for L at increasing times disclosed that the attack on the cis CH=CHCH2CH=CH moiety by OCl- does not follow simple second-order kinetics. Using a logit-log transform and second-order polynomial regression analysis of L's disappearance in a stoichiometric ([L] = 1.2 mM; [ClO-] = 2.4 mM) mix, data were analyzed by the time ratio method of Schwemer and Frost. These agreed with a sequential system of at least two irreversible second-order reactions having k1 = 15.6 L.mol-1.s-1 and k2 = 2.6 L.mol-1.s-1. Preliminary GC/MS analysis indicated that the initial product is a mix of chlorohydrin isomers. These undergo second addition of HOCl and/or lose halogens and polymerize. Additional minor products were also C5-C9 mono- and bifunctional carboxylates and mixed acid aldehydes. Studies with mol equiv of Cl- - free 36ClO- allowed estimation of covalent binding of Cl by L at various times, supporting the kinetic findings. For other PUFAs of higher degree unsaturation, the complexity of feasible reactions precluded an analogous approach.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1504267 TI - Inactivation of alpha 1-proteinase inhibitor by peroxynitrite. AB - We here report the reactions of peroxynitrite (O=NOO-) with alpha 1-proteinase inhibitor (alpha 1PI) and with a synthetic decapeptide (MER10) containing the sequence of amino acids found in the active site of alpha 1PI (Pro-Met-Ser-Ile Pro-Pro-Glu-Val-Lys-Phe). Peroxynitrite inactivates alpha 1PI at both pH 7.4 and 12.0. Thiourea and methionine protect alpha 1PI against inactivation by peroxynitrite, while mannitol and benzoate fail to afford effective protection. The major product isolated from the reaction between peroxynitrite and MER10 was analyzed by NMR, mass spectrometry, and amino acid analysis. These analyses indicate that peroxynitrite primarily oxidizes the methionine residue in the peptide. We detect neither smaller molecular weight peptides, which would indicate cleavage of MER10, nor hydroxylation or nitration of the phenylalanine residue. Our results suggest that peroxynitrite is capable of oxidizing methionine residues in proteins without the involvement of the hydroxyl radical or nitrogen dioxide. The implications of these observations on lung diseases attributed to cigarette smoke are discussed. PMID- 1504268 TI - Mutagenic activation of benzidine requires prior bacterial acetylation and subsequent conversion by prostaglandin H synthase to 4-nitro-4' (acetylamino)biphenyl. AB - We have used the Ames test in combination with prostaglandin H synthase (PHS) to study the bioactivation of benzidine as well as other aromatic amines. Previous investigations established that the formation of benzidine mutagens by PHS is dramatically enhanced in Salmonella typhimurium strains with high levels of acetyl CoA-dependent arylamine N-acetyltransferase/arylhydroxylamine O acetyltransferase activity despite the fact that acetylation of aromatic amines decreases their susceptibility to oxidation by peroxidases. In this study, we used a new strain (YG1012) that has very high acetylation capability to investigate the metabolism and mutagenicity of benzidine and N-acetylbenzidine catalyzed by PHS (from ram seminal vesicle microsomes) and horseradish peroxidase (HRP). YG1012 bacteria rapidly acetylated benzidine to N-acetylbenzidine and N,N' diacetylbenzidine. Preincubation of the bacteria with benzidine before addition of PHS increased the mutagenicity. Under conditions identical to those used to assess mutagenicity, PHS metabolized benzidine rapidly, but the substrate was not totally consumed, with about 40% of the original concentration remaining intact. These data suggest that conversion to N-acetylbenzidine may be the initial step in the bioactivation of benzidine in the PHS-mediated Ames assay. N Acetylbenzidine is a cosubstrate for PHS peroxidase activity as measured by 5 phenyl-4-pentenyl hydroperoxide reduction, spectral changes, and formation of protein adducts. N-Acetylbenzidine was converted to mutagens by PHS but not HRP, with enhanced mutagenicity observed in bacteria with high acetylation activity. We used reverse- phase HPLC to characterize the metabolites of N-acetylbenzidine formed by PHS and HRP.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1504269 TI - Update on oral contraceptive pills and postcoital contraception. AB - Modern oral contraceptive pills are safe for the majority of American women. The most important contraindications to oral contraceptive pill use are a history of thrombophlebitis or thromboembolism while on the pill or during pregnancy, smoking over 15 cigarettes daily if over 35 years of age, active liver disease, hypertension, diabetes, a lipid disorder, or breast cancer. A history of gestational diabetes is not an absolute contraindication to oral contraceptive pill use, but women with such a history must be encouraged to exercise and eat properly to reduce the high risk of developing overt diabetes. Couples should be encouraged to use condoms to reduce the risk of sexually transmitted diseases. Most antibiotics do not decrease the effectiveness of the pill. Nonuse of contraception among adolescents and older couples is the most common reason for failure. Postcoital contraceptive pills are available but are not completely effective. The use of modern contraceptives is almost always safer than nonuse. PMID- 1504270 TI - Abortion: epidemiology, safety, and technique. AB - In 1991, the abortion literature was characterized by articles relating to 1) epidemiologic issues in abortion care, 2) advances in knowledge and experience with medical abortifacients such as mifepristone (RU 486), and 3) cervical ripening prior to abortion with the use of both mifepristone and prostaglandins. Technical methods of achieving termination of pregnancy continue to be similar in the United States, the United Kingdom, and Europe, although induction-abortion times are generally slower in Europe than in the United States. Surgically, dilatation and evacuation procedures continue to be more common in the United States than in other countries. The effectiveness of mifepristone is undisputed, and the recommended dose for early first-trimester termination is being compared with lower dose alternative regimens. There is additional evidence that at least in the short term, the negative psychological sequelae of abortion are infrequent and are inconsequential as a public health issue. PMID- 1504271 TI - New condoms for men and women, diaphragms, cervical caps, and spermicides: overcoming barriers to barriers and spermicides. AB - Barriers and spermicides are being developed for the prevention of unwanted pregnancy and sexually transmitted infection. The inconvenience of current methods limits their acceptability and leads to higher user failure rates. New methods, such as female condoms, nonlatex male condoms, and new cervical caps are being developed: the Reality (Wisconsin Pharmacal, Jackson, WI) polyurethane vaginal pouch has already received conditional Food and Drug Administration approval for use in the United States. The material used in a Food and Drug Administration-approved nonallergenic glove is being tested for its effectiveness as a condom. In addition, the Fem Cap, a cervical cap that had a life table probability of failure within 1 year of 4.8%, is expected to be available within the next 2 years. It is important for clinicians to be informed of new options becoming available for those patients who may be good candidates for these barrier methods. PMID- 1504272 TI - Future directions in contraception. AB - Although contraceptive research has markedly decreased in the United States, it has continued in other countries. The emphasis has been on the development of long-acting, noncoitally related contraceptives, including the progestogen-only and progestogen-estrogen vaginal rings. The levonorgestrel-releasing intrauterine device is highly effective and, like other contraceptives, may contribute to a decrease in the incidence of pelvic inflammatory disease. There is a great need for more effective, acceptable barrier contraceptives. The vaginal condom does not appear to be acceptable to many couples. Studies continue to demonstrate couples' lack of adherence to plans for abstinence and poor utilization of the present barrier contraceptives. The potential for the development of a male contraceptive utilizing gonadotrophin hormone-releasing hormone agonists or antagonists in conjunction with testosterone may hold promise in the future. PMID- 1504274 TI - Surgical treatment and complications of urinary incontinence. AB - Numerous surgical approaches to the management of incontinence, particularly genuine stress incontinence, have been reported. No single operation is a panacea for the condition, and many factors must be taken into account before deciding which procedure is best tailored to an individual's needs. The procedures vary in their results, morbidity, and associated complications. Awareness of these previous complications encourages their avoidance and permits better management should they occur. PMID- 1504273 TI - Investigative techniques, assessment of incontinence, and urodynamics. AB - The past year's literature reflects a continued interest in studying and refining standard investigative techniques, both urodynamic and radiographic, that have long been used to evaluate patients with lower urinary tract dysfunction. In addition, new, simple, and inexpensive technologies that allow relatively accurate diagnosis and that minimize medical costs have been introduced. These continued efforts to understand the pathophysiology of the lower urinary tract better bring both the practicing physician and the urogynecologist closer to making correct diagnoses and appropriate therapeutic decisions. PMID- 1504275 TI - Idiopathic fecal incontinence. AB - Pelvic floor dysfunction is related to neuropathic injury to the pelvic floor musculature. Clinically, the patient may present with genital prolapse or urinary or fecal incontinence. For a successful outcome, the physician must consider all pelvic compartments in the evaluation and treatment of patients with these disorders. Disorders of the posterior compartment are the least familiar to the gynecologist. Idiopathic fecal incontinence, a posterior compartment defect, is defined as a progressive deterioration of anal sphincter function in patients with no history of sphincter damage. This review discusses the latest findings about idiopathic fecal incontinence within the context of pelvic floor dysfunction and neuropathy. PMID- 1504276 TI - Lower urinary tract infection in women. AB - Infections of the lower urinary tract affect 10% to 20% of all women, among whom a substantial proportion go on to experience recurrent infections. Bacterial virulence factors, particularly those enhancing mucosal adherence, are important in the pathogenesis of urinary tract infection. The use of a diaphragm with spermicides predisposes to urinary tract infection, most likely through alterations of the normal vaginal flora. Urine microscopy is the most accurate rapid office test for urinary tract infection. Automated and dipstick techniques yield slightly lower sensitivity and specificity. Recent treatment trials indicate that 3-day therapy for uncomplicated lower urinary tract infection provides an optimal balance between efficacy and adverse effects when compared with single-dose therapy or treatment for 7 to 10 days. Antibiotic prophylaxis is an important strategy in treating recurrent infections and is effective for periods as long as 5 years without undue emergence of resistant bacterial strains. Interstitial cystitis remains an elusive entity without definite diagnostic criteria or clearly effective therapy. PMID- 1504277 TI - Gynecologic pathology. PMID- 1504278 TI - Malignant endometrial pathology. AB - This review discusses recent papers on endometrial carcinoma variants, immunohistochemical studies, and prognostic indicators. The aggressive nature of uterine papillary serous carcinoma is confirmed, even in the absence of myometrial or vascular invasion, with a comprehensive review of the histology, clinical presentation, and proposed treatment protocols. The possible etiologic role of radiation in the development of uterine papillary serous carcinoma is alluded to. The virulence of endometrial carcinomas with trophoblastic differentiation, endometrial carcinomas with a malignant giant cell component, and clear cell carcinomas of the endometrium is documented. A series of immunohistochemical studies is presented suggesting that uterine carcinosarcomas are metaplastic carcinomas derived from a common stem cell and that a shared histogenesis of endometrial stromal tumors and uterine mesoderm exists. Immunohistochemical techniques may clarify diagnostic problems of uterine tumors and their metastases and differentiate mucinous tumors of endometrium from endocervical origin. Staining of both carcinoembryonic antigen and ferritin in neoplastic endometria may be helpful in their differentiation from hyperplasias in curettage specimens. Significant prognosticators in endometrial carcinoma are depth of myometrial invasion and lymphovascular space involvement with greatest prognostic information provided by the depth of myometrial invasion above DNA index. PMID- 1504279 TI - Benign and malignant breast pathology. AB - Research is focused on defining high-risk factors associated with the development of breast cancer and occult metastatic disease in node-negative patients. The interaction between hormones and growth factors is being diligently investigated, both in the genesis of breast cancer and in metastases. The effect of oral contraceptives on breast pathology remains under close scrutiny. Screening mammography for young women is proving to be of doubtful value. PMID- 1504281 TI - Family planning. PMID- 1504280 TI - Ovarian pathology. AB - During the period under review (December 1990 through January 1992), the revised World Health Organization Histological Classification of Ovarian Neoplasms and Tumor-like Lesions was completed, and it is presented herein. This system of classification incorporates recent advances and includes newly recognized entities and subtypes. A number of significant reviews covering the whole field of ovarian tumor pathology have been published, including reviews of clinical syndromes associated with ovarian neoplasia, metastatic tumors of the ovary, and the interrelationships between ovarian and appendiceal mucinous tumors and pseudomyxoma peritonei. PMID- 1504282 TI - Gynecologic urology. PMID- 1504283 TI - Gynecologic pathology. PMID- 1504284 TI - Measurement in psychogeriatrics. AB - Stake's concept of Responsive Evaluation is applied in evaluating the chain of psychogeriatric services of a general psychiatric hospital. Central to the approach presented are methodological considerations in describing individual treatment courses in their objective and subjective features. This can only be accomplished by establishing multidimensional strategies, incorporating biological, mental, psychological, and sociocultural aspects. PMID- 1504285 TI - Treatment of behavioral symptomatology of Alzheimer's disease, with emphasis on aggression: current clinical approaches. AB - A scientific information base is developing which focuses on understanding and managing behavior problems in geriatric populations, especially those with dementing illnesses such as Alzheimer's disease. Many of these behavior problems occur in long-term care settings, which have a high prevalence of residents exhibiting emotional and behavioral disorders, often secondary to psychiatric illness. Prior to beginning treatment, behavior disorders must be systematically evaluated and understood to insure optimum care planning. One approach to effectively treating these disorders is to first separate them into two categories: those not amenable to psychotherapeutic medication treatment (nonpsychiatric disorders) and those that are amenable (psychiatric disorders). Specific nonpharmacological treatments may benefit those nonpsychiatric behavioral disorders and include behavioral and environmental paradigms. The psychiatric disorders, especially aggression and assaultive behavior, may be treated beneficially using a variety of psychopharmacological agents, including antianxiety agents, neuroleptics, carbamazepine, beta-blockers, and lithium. The most effective approach toward treating the psychiatric behavior disorders often combines both medication and nonmedication strategies. PMID- 1504286 TI - Psychiatric phenomena in dementia of the Alzheimer type. AB - Psychiatric symptoms and behavioral disturbances are of importance in dementia of the Alzheimer type (DAT) but have been relatively neglected by researchers. The main psychiatric symptoms are disorders of thought content (delusions and paranoid ideation), disorders of perception (hallucinations and misidentifications) and disorders of affect (depressed and elevated mood). They occur commonly in DAT, and there is evidence that they may indicate subtypes of the disorder in view of their demographic, structural, and prognostic correlates. Personality changes are very common, and these may be the earliest manifestation of dementia. Behavioral disturbances tend to be associated with advanced dementia and are particularly disruptive to caregivers. Structural correlates suggest that some behaviors are a direct result of brain damage. Psychiatric and behavioral features in DAT are important, as they may serve as a model for symptomatology in functional psychiatric disorders. PMID- 1504287 TI - Alzheimer's disease--clinical course: methodologic implications for pharmacologic trials. PMID- 1504288 TI - Functional assessment staging (FAST) in Alzheimer's disease: reliability, validity, and ordinality. AB - Evaluation of changes in functional performance and activities of daily living skills is an essential aspect of the assessment of elderly individuals with chronic illness. Although functional decrement is a central aspect of Alzheimer's disease (AD), many measures currently utilized to assess these changes have limitations. Empirical and systematic examination of the functional changes occurring in patients with AD has resulted in the development of an assessment measure termed Functional Assessment Staging (FAST) that allows for the specific evaluation of these changes throughout the entire course of AD. In this paper the results of three separate investigations regarding the reliability, validity, and progressive ordinality of FAST are described. The results indicate that FAST is a reliable and valid assessment technique for evaluating functional deterioration in AD patients throughout the entire course of the illness. Moreover, the results suggest that the FAST elucidates a characteristic pattern of progressive, ordinal, and functional decline in AD. Because the elements of functional capacity incorporated in FAST are relatively universal and readily ascertainable, as well as characteristic of the course of AD, FAST can serve as a strong diagnostic and differential diagnostic aid for clinicians. The sensitivity of FAST to the entire course of AD, even in its most severe stages, may be indicative of the potential value of this instrument for further investigation of the temporal longitudinal course of AD, and of the relationships between clinical pathology and neuropathology throughout the entire longitudinal course of AD. PMID- 1504289 TI - Functional rating scales and psychometric assessment in Alzheimer's disease: applications in pharmacological trials. AB - New findings on cognitive aging show that decline in brain functions is not part of a general decline of functioning in old age. We know now that with increasing age there is a differentiation of cognitive functions into two independent dimensions (fluid and crystallized functions). This two-dimensional model allows a more precise description of the cognitive aging process and of pathological changes. While crystallized cognitive abilities can be improved by training till late in life, fluid cognitive functions are subject to a progressive decrease starting as early as age 30, becoming most evident in cases of organic mental disorders. Thus, pathological aging is not necessarily accompanied by global loss of functions. Different abilities undergo changes in different ways, a fact taken into consideration by modern methods of psychometric evaluation. Beyond the aging processes mentioned previously, cognitive and behavioral changes in the elderly may be considered to be early indicators of organic mental disorders. The Nuremberg Self-Evaluation List seems to be a promising approach to diagnosis. PMID- 1504290 TI - Global rating, symptoms, behavior, and cognitive performance as indicators of efficacy in clinical studies with nimodipine in elderly patients with cognitive impairment syndromes. AB - Nimodipine is a calcium antagonist which improves learning and memory in brain lesioned or aged animals (LeVere & Sandin, 1989; Schuurman & Traber, 1989). It also accelerates the recovery of experimentally damaged sciatic nerves (van der Zee et al., 1987) and reduces age-associated gait abnormalities in aging rats (Schuurman et al., 1987). Selective action on cerebral vessels has also been proven. Vasoconstriction was prevented or reduced with nimodipine under experimental conditions (Toward, 1981) and cerebral blood flow could be increased (Kazda et al., 1982). The drug has been tested in subarachnoid hemorrhage, stroke, severe head injury, cerebral resuscitation after cardiac arrest, impaired brain function in old age, and dementia. Methodological aspects of clinical studies with this agent are examined in this paper. PMID- 1504291 TI - Pharmacologic treatment of Alzheimer's disease: a methodologic critique based upon current knowledge of symptomatology and relevance for drug trials. AB - Research on the nature of clinical symptomatology in AD indicates that two fundamentally different types of symptoms are identifiable. Symptoms within each of these two domains have common characteristics. The first symptomatic domain has been termed the "cognitive domain" and the second the "noncognitive behavioral domain." Symptoms and losses in the cognitive domain occur invariably and progressively with the advance of AD over time. Symptoms in the behavioral domain do not invariably occur in AD and do not progress monotonically with the advance in AD over time. However, characteristic behavioral domain symptoms can be described over the course of AD. The two symptomatic domains are likely to differ not only in nature and progression in AD, but also in underlying pathophysiology and in terms of possible treatment modalities. They also pose fundamentally different issues of assessment in AD. These distinct factors necessitate the separate assessment of the two symptomatic domains in AD treatment trials. Judgments of efficacy and utility in remediating either symptomatic domain in AD should take into consideration the effects of treatment on both cognitive domain and behavioral domain symptoms separately and interactively. Appropriate assessment procedures are discussed. PMID- 1504292 TI - The fifth business. PMID- 1504293 TI - HIV testing and life insurance. PMID- 1504294 TI - A comparative study of the maximum oxygen uptake of regularly exercising and non exercising health adult men in sedentary occupations. AB - This study aims to assess and compare the aerobic fitness (max VO2) of 210 healthy adult men in sedentary occupations in Singapore. All the subjects studied were in codes 0 to 2 of the Singapore Standard Occupational Classification, comprising professional, technical, administrative and related workers. Their max VO2 were determined from direct analyses of their expired respiratory gases during an all-out run on a treadmill. Of these 210 men, 71 (33.8 per cent) were recreation-related regular exercisers and their mean max VO2 of 40.9 ml/kg per min STPD (at standard temperature and pressure, dry) and 95 per cent confidence interval of 39.2-42.6 ml/kg per min was significantly higher (p less than 0.001) than that of the remaining 139 men (34.3 ml/kg per min STPD) with 95 per cent confidence intervals of 33.2-35.4 ml/kg per min who were not regular exercisers. The regular exercisers also met the max VO2 requirements for heavy physical work capacity and compared favourably with the recommended standards for aerobic fitness in the National Physical Fitness Award of Singapore as well as Cooper's Standards based on North American men while the non-regular exercisers did not. The study has shown that the recreation-related regular exercise of the study defined type, intensity, duration and frequency can significantly improve the physical work capacity of healthy adult men in sedentary occupations in Singapore. PMID- 1504295 TI - Mortality of urban transit workers: indications of an excess of deaths by suicide using gas. AB - Urban bus drivers are exposed to a variety of discomforts and physical hazards associated with their occupation. We obtained death certificates for 99 per cent of 219 decreased members of the Amalgamated Transit Union Local 596 of Edmonton, Alberta, and conducted a proportionate mortality study against the distribution of all deaths among men in the province of Alberta, standardized by age and year of death. We found a highly significant excess from undetermined accidents due to gas (proportionate mortality ratio (PMR) 3761, based on 3 cases; p less than 0.003), which may bear a relationship to an elevation observed for suicide due to gas, which failed to achieve statistical significance (PMR 242, based on 2 cases). Collateral evidence suggests that this excess may include misclassification of some suicides. Gas inhalation as an instrument of suicide may be suggested by familiarity with vehicle exhaust. No other excess achieved statistical significance. Several causes of death showed elevated PMRs of relatively modest magnitude; elevations in PMR for lung cancer (PMR 154) and chronic obstructive pulmonary disease (PMR 176) suggest a mutual association with smoking. PMID- 1504296 TI - Workplace upper limb disorders: a prospective study with intervention. AB - A prospective longitudinal study was carried out to investigate the occurrence of upper limb disorders in an electromechanical plant between 1980 and 1988. It included clinical and epidemiological studies, measurement of vibration produced by the power tools used, ergonomic assessment of the works and time and motion studies. Simultaneously during the same period remedial actions were taken through multidisciplinary interventions when the specific causal factors were known. The study shows the clinical entities of the disorder, identifies the risk factors and evaluates the results of the interventions. It assists in establishing a cause and effect relationship for the condition and demonstrates the way a preventive strategy could be developed. PMID- 1504297 TI - Epilepsy and employability: a comparative evaluation of epileptic employees working in the steel plants of India. AB - Information on seizures and provoking factors, occupational status, shift work, overtime, home and work place adjustment was obtained from 176 epileptic employees working in hazardous, less and non-hazardous areas of steel plants in India. Accidents at work and sickness absence were also assessed in 44 epileptics. An overall comparison was made between Group A hazardous (63) and Group B less/non-hazardous (76) of the total of 139 epileptic employees over a three year period. Group A performed better than Group B. When compared with 77 employees with occupational dermatoses, 139 epileptics did more fixed shifts and had less promotion. PMID- 1504298 TI - Causes of hypersensitivity reactions in flour mill workers in Sudan. AB - A study of 237 male workers at two flour mills and 71 controls was carried out in Sudan in order to investigate the main possible causes of hypersensitivity reactions to flour dust. Statistical analysis was carried out for the skin test results of wheat, mixed moulds (A13), grain dust, and mixed moulds (group MH) allergen extracts. The results showed that there was no statistical significance between the two exposed groups namely allergy complaining vs. allergy non complaining except for wheat results in one of the two flour mills which was very slightly significant. But there were highly significant differences between the exposed compared with the control group in all allergens tested. There was no significant correlation, between allergic symptoms and precipitins to wheat or grain dust, nor between precipitins and positive skin tests. The results of respirable flour dust concentrations at different work locations had exceeded the threshold limit values which were taken as 10 mg/m3. Aspergillus supp. and Rhizopus niger were the predominant fungi in the wheat grains and products which were collected from the two mills. PMID- 1504299 TI - Vision assessment for display screen users: a hospital-based study. PMID- 1504300 TI - Management of post-incident trauma: a fire service perspective. AB - Post-incident trauma relates to the results of exposure to death and destruction. It has specific features relating both to the incident and symptoms it produces. Reactive symptoms occur in most people in the immediate after-period but rising or persisting anxiety towards the end of the first week indicates a risk of a serious disorder developing. Management should start immediately after the event and is a three stage process. Immediate management involves de-briefing and peer group support of the participants in the incident. For those who continue to experience rising or persisting anxiety after the first week, referral to occupational health advisers, welfare/counsellors or general practitioners is necessary and, if symptoms persist or recur, tertiary referral to specialist advisers such as psychologists or psychiatrists may be required. The most important factor in the treatment of post-incident trauma is to acknowledge its existence. Whilst the coping mechanisms are well established in theory, they require widespread implementation in practice. PMID- 1504301 TI - Does RSI exist? PMID- 1504302 TI - An evaluation of several laboratory tests and test combinations in the detection of lupus anticoagulant. AB - The laboratory assessment of the lupus anticoagulant, a factor frequently associated with venous and arterial thrombosis, recurrent miscarriages and abortions, is not straightforward, as indicated by the variety of tests proposed and the different results obtained. On account of the marked variability and heterogeneity of lupus anticoagulant among patients, no single test or reagent will identify all patients with lupus anticoagulant, and a panel of several tests has to be used. This is time consuming and increases the workload of the laboratory. The aim of this study was to assess the minimum number of tests necessary for the satisfactory identification of the patient with lupus anticoagulant. Our study confirms that lupus anticoagulant may be present in a significant number of patients with normal routine activated partial thromboplastin time, a test which therefore cannot be used as the sole criterion for identifying patients suspected of having lupus anticoagulant. In contrast all patients who had positive results in at least one test could be detected (100% sensitivity) with two combinations of tests: (1) dilute activated partial thromboplastin time and Kaolin clotting time and (2) dilute activated partial thromboplastin time and tissue thromboplastin inhibition test. Since the latter inhibition test has been reported to give a high number of false-positive or negative results, we suggest the combination of dilute activated partial thromboplastin time and Kaolin clotting time as the standard pair of tests for the screening of suspected lupus anticoagulant patients. PMID- 1504303 TI - Evidence that factor VII levels correlate strongly with fibrinopeptide A release: evaluation by an ex vivo method. AB - The generation of thrombin was estimated by an assay for fibrinopeptide A which was developed and employed to evaluate the relationship between factor VII and thrombin release. The amount of fibrinopeptide A released correlated strongly, when assayed in the early stages of the reaction, with factor VII coagulant activity levels in the range 50-2,000 units/dl. The method was then applied to study the relationship between factor VII and fibrinopeptide A in plasma from blood donors, women on the pill and patients on oral anticoagulants (with a range of factor VII coagulant activity from 8.5 to 600 units/dl). The overall evaluation of the relationship between factor VII and fibrinopeptide A showed a strong correlation which was higher for factor VII coagulant activity (r = 0.90) than for factor VII antigen levels (r = 0.817). The regression analysis which best fitted the data was the multiplicative one, indicating that thrombin formation increases faster when factor VII coagulant activity is in the upper part of the normal range or higher. In patients on oral anticoagulants, the correlation between factor VII and fibrinopeptide A was very poor. Our data fit well with the findings of the epidemiological studies in which high levels of factor VII coagulant activity were shown to be associated with an increased incidence of fatal coronary artery disease. PMID- 1504304 TI - The effects of lipoproteins on the tissue factor-dependent activation of factor X. AB - We examined the effect of the lipoproteins on the activation of human factor X in an in vitro system containing purified human factor VII, low levels of tissue factor and calcium ions. In the absence of the lipoproteins the maximum activation was achieved within 10 min of the start of incubation; after this period the formation of factor Xa ceases. When very low-density lipoproteins, low density lipoproteins or high-density lipoproteins were present at normal or subnormal plasma concentrations, the factor Xa generated was almost doubled after 10 min. This increase could be abolished by treating each lipoprotein subfraction with the phospholipase A2; hence, the treated lipoproteins lowered the factor Xa activity. We conclude that the phospholipids favor factor Xa formation and protect the tissue factor/factor VIIa/factor Xa complex from a potent inhibitor contained in the lipoprotein subfractions. PMID- 1504305 TI - Molecular characterization of the P and I variants of alpha 1-antitrypsin. AB - Two rare alpha 1-antitrypsin variants, Pi I and Plowell, originally defined at the protein level through isoelectric focusing, were characterized at the DNA level by the polymerase chain reaction and direct sequencing. The I variant was confirmed in one individual and three independent families to result from a CGC(Arg) to TGC(Cys) transition at codon 39, within exon II. In our population, the Pi I variant might be more common than expected. The Plowell allele was shown in one M3P heterozygous individual to be due to a GAT(Asp) to GTT(Val) change at codon 256, in agreement with a previous study based on hybridization with allele specific oligonucleotides. PMID- 1504306 TI - Is therapy with cytostatics obsolete in hairy-cell leukemia? PMID- 1504307 TI - Molecular economy and antibody function: the evolution of a Protecton. AB - The humoral immune response protects against a very large array of pathogens which attempt to escape immune recognition by changing the antigens they display. When looked at from the point of two competing sets of DNA (i.e., the pathogens vs. the host), there is a vastly larger pool of mutating pathogen DNA than in, say, a mouse. The stratagems that allow a tiny fraction of the mouse's genome to effectively compete with a hugely diverse array of pathogens is analyzed in terms of how antibody functions and how the immune system avoids such pitfalls as self recognition and destruction. This review is a more general description of a lengthy series of papers which detailed the evolution of the Protecton. Starting from the obvious, that is the concentration-dependence of antibody function, it is apparent that the functional antibody repertoire must be relatively small if a sufficient concentration of specific antibody is to be produced in time to arrest the growth of pathogens and eventually eliminate them. Thus, commonly quoted estimates of antibody repertoires in the range from greater than 10(10) to "complete" (infinite?) must be seriously in error. Other well known "facts", such as D-diversity, and B cell signaling by receptor aggregation are also shown to be lacking in biological commonsense. PMID- 1504308 TI - Cell adhesion molecules in neoplastic disease. AB - In a variety of human malignancies, tumorigenesis and the development of metastatic disease are accompanied by changes in the expression of cell adhesion molecules. In carcinomas, normally expressed cell adhesion molecules are lost, or expressed in a functionally altered form, events which may help tumor cells to escape from contact-mediated controls and leave the primary tumor. The development of metastatic potential is, in a number of solid tumors, associated with the expression of new cell adhesion molecules by the tumor cells. These newly expressed cell adhesion molecules appear to mediate tumor cell interaction with leukocytes and endothelium, and may direct dissemination of the tumor cells throughout the body. PMID- 1504309 TI - CD38: a multi-lineage cell activation molecule with a split personality. AB - This review reports the characteristics of the human surface molecule CD38, a structure not linked to a definite line and predominantly expressed in early and activated phenotypes. The CD38 molecule consists of a single chain of 46 kDa, spanning the membrane and with the carboxyl terminus located in the extracellular compartment. The CD38 molecule is also involved in the transduction of activation and proliferation signals, which are line unrestricted. The gene coding for the CD38 antigen has been cloned and used for the construction of simian and mouse transfectants expressing the human molecule. These cell models are used for the analysis of several unanswered issues, mainly concerning the in vivo function of CD38, the existence of a natural ligand and of polymorphism in the population. PMID- 1504310 TI - Update on tumor vaccines. AB - Vaccination against tumor has always been an attractive idea for the treatment of patients bearing tumor. By harnessing the host's own immune response the attack on tumor cells would act on a continuing basis, with emerging tumor cells stimulating their own destruction. However, the approach has been hampered by our poor understanding of the nature of tumor antigens and of the pathways by which immune cells might operate against tumor growth. Recent developments in molecular biology and immunology are remedying this deficiency and bringing vaccination to the forefront of new approaches to treatment of a range of tumors. Results obtained in B-cell tumors, where the idiotypic immunoglobulin at the cell surface provides a well-defined tumor antigen, are already indicating exciting possibilities as well as delineating problems. There is considerable clinical evidence that patients have some intrinsic ability to control tumor growth and that certain tumors remain dormant for long periods. Attempts to understand and perhaps stimulate the mechanisms involved are being made through the use of biological modifiers and by manipulating potential effector cells in vitro. Ideally this approach, which may include non-specific and specific elements, could be combined with specific vaccination in order to combat the apparent ability of many tumor cells to evade host defences. PMID- 1504311 TI - Are heat shock proteins involved in autoimmunity? AB - Heat shock proteins (HSPs) have been postulated to be critical antigens in both autoimmune disease and experimental models of autoimmunity. This postulate has been largely based on the remarkable conservation of aminoacid sequence between human and bacterial HSPs, so that it has been argued that immune responses initially directed against the HSP of an infectious agent, would have the potential to initiate or maintain autoimmune disease. This would apply especially to T cell recognition of HSPs, since the T cell focuses on short peptide epitopes within a protein antigen rather than on the antigen's secondary structure. This article critically evaluates the available experimental evidence relating to this hypothesis: although research has clearly highlighted the central role of HSPs in the cellular immune response to pathogenic organisms and has shown the potential for T cell responses directed against self HSPs, a role for self HSPs as major target antigens in autoimmune disease has yet to be firmly established. PMID- 1504313 TI - Change: both a reality and a challenge. PMID- 1504312 TI - Symptoms of a troubled nation. PMID- 1504314 TI - Nursing's agenda for health care reform: a critique. AB - This paper discusses the nature of the health care crisis with a focus on the issues of economics, the private insurance industry, race and ethics as they relate to Nursing's Agenda for Health Care Reform. Recommendations are made for assuring the entire population quality, equitable health care. PMID- 1504315 TI - Predicting nursing student's success on NCLEX-RN. AB - The purpose of this retrospective pilot study was to evaluate the importance of four predictor variables in predicting success on the NCLEX-RN. The predictor variables included: pre-nursing GPA, ACT scores, comprehensive examination scores and scores on the Basics I, NLN Achievement Test. The subjects were a sample of 35 graduates of a newly developed baccalaureate nursing program. Findings of this study were inconclusive. Basic I test scores were significantly correlated with successful achievement on the NCLEX-RN and were significant predictors of success. The other variables were not significant predictors. Recommendations were to repeat the study with a larger sample. PMID- 1504316 TI - Many different health problems confronting African American communities. PMID- 1504317 TI - Storage proteins are present in the hemolymph from larvae and adults of the Colorado potato beetle. AB - The protein composition of larval and adult hemolymph from the Colorado potato beetle, Leptinotarsa decemlineata, was investigated and some abundant, high molecular weight proteins were identified and characterized. Diapause protein 1, which occurs in the hemolymph of last instar larvae and short-day adults, appeared to be a storage protein. This protein dissociated into two bands due to the high pH used in nondenaturing gels. Its quaternary structure was established by chemical crosslinking. It appeared to be a hexamer. Diapause protein 1 is composed of approximately 82,000 subunits. The amino acid composition and N terminal sequence of this protein has been determined. Specific antibodies against diapause protein 1 have been developed. Topical application of 1 microgram pyriproxyfen, a juvenile hormone analog, to last instar larvae and short-day adults suppressed the appearance of this protein in the hemolymph. Pyriproxyfen prematurely induced vitellogenin, when applied to last instar larvae. A larval specific protein was also identified in the hemolymph. Its temporary appearance in the hemolymph of last instar larvae, its subunit composition (M(r) approximately 82,000) and its suppression by pyriproxyfen suggests that this protein is a storage protein as well. PMID- 1504318 TI - Infradian cycles of oxygen consumption in diapausing pupae of the flesh fly, Sarcophaga crassipalpis, monitored by a scanning microrespirographic method. AB - Fine details of the infradian O2 consumption cycles that characterize pupal diapause in flesh flies have been monitored by a newly designed microrespirographic method coupled with an electronically regulated O2 generator. During the 4-5 days between the peaks of elevated O2 consumption, the diapausing pupae maintained a very low and fairly constant respiratory rate (13 microl O2 x g-1.h-1). During the intercalated peaks of increased respiratory metabolism, which lasted an average of 33.6 h to 24-27 degrees C, the average maximum rate of O2 consumption was 86.9 microl.g-1.h-1, a value of 6.7 times higher than the interpeak values. The respiratory peaks started abruptly in some cases while the decline was consistently gradual. During the periods between the peaks there were no discontinuous bursts of CO2 release, a feature common to diapause in many other insects. Diapause was characteristically terminated during a peak of the O2 consumption cycle. At diapause termination O2 consumption remained at the maximum values of the peak for many hours and then gradually increased to levels characteristic of nondiapause development. PMID- 1504319 TI - Separation of insect hemolymph proteins by cascade-mode multi-affinity chromatography. AB - The hemolymph of the adult female Manduca sexta was fractionated by cascade-mode multi-affinity chromatography (CASMAC) on a main-line tandem column chain containing Zn(2+)-TED, T-gel, Ni(2+)-DPA, and phenylsepharose and a side-line column containing Zn(2+)-DPA. The technique separated some of the previously described major hemolymph proteins, and yielded a number of fractions with simple composition. Some of these fractions contained only less abundant proteins of Manduca hemolymph. Thus, it appears that CASMAC would be a very useful fractionation technique for purification and characterization of the minor proteins of insect hemolymph. PMID- 1504320 TI - Allatostatins in the nerves of the antennal pulsatile organ muscle of the cockroach Diploptera punctata. AB - The presence of allatostatins in the nerves of the antennal pulsatile organ muscle of the cockroach Diploptera punctata was confirmed by immunocytochemistry, bioassay, and HPLC. Immunocytochemical reactivity with monoclonal antibody against allatostatin I showed strong allatostatin immunoreactivity in the antennal heart nerve which innervates this muscle with varicosities along the muscle fibers and in the insertion of the muscle on the pulsatile ampullae. Bioassay of Sep-Pak purified muscle extract demonstrated inhibition of juvenile hormone synthesis by corpora allata in vitro. A dose-response curve showed maximum inhibition of juvenile hormone synthesis was achieved with 10-20 pulsatile organ muscle eq/corpora allata, and 50% inhibition achieved with an estimated 2.6 pulsatile organ muscle eq. Two successive HPLC separations of the Sep-Pak purified extract yielded bioactive fractions corresponding to the elution times of the five known allatostatins. PMID- 1504321 TI - Role of phospholipids in the lipophorin particles of Rhodnius prolixus. AB - The lipophorin of Rhodnius prolixus metabolically labelled with 32P exclusively in the phospholipid moiety was purified on a potassium bromide gradient and treated with phospholipase A2 in the presence of an excess of fatty acid-free albumin. The treatment completely removed the phospholipids from the particles and generated [32P]-lysophosphatidylcholine, [32P]-lysophosphatidylethanolamine, and free fatty acids that remained bound to albumin. The phospholipid-depleted lipophorin particles remained soluble, indicating that phospholipids are not essential in maintaining the stability of the particles in aqueous solution. Complete removal of phospholipids did not affect the association of apolipophorin III with lipophorin particles. Lipophorin density increased slightly from 1.120 to 1.134 g/ml after treatment. The phospholipid-depleted particles also retained their ability to be recognized and loaded in vitro with phospholipids delivered by the fat body, thus supporting the concept of lipophorin's role as a reusable lipid shuttle for phospholipids. PMID- 1504322 TI - Storage proteins of the larval root weevil Diaprepes abbreviatus (Coleoptera: Curculionidae): riboflavin binding and subunit isolation. AB - Proteins present at high concentrations in hemolymph of the larval weevil Diaprepes abbreviatus were previously shown to bind a synthetic coumarin, 7-amino 3-phenyl coumarin (coumarin-10). One of the two native proteins previously identified (protein I) is now shown to separate into two distinct bands (proteins Ia and Ib) using native gradient pore-limiting electrophoresis. The high concentration of proteins Ia, Ib, and II in larval hemolymph, their disappearance from hemolymph upon pupation, and an apparent hexameric structure shown by chemical crosslinking identify them as hexameric storage proteins (hexamerins). At least one chromatographic form of Ib isolated by anion exchange HPLC is now shown to bind riboflavin (Rb). Binding was also demonstrated by quenching of Rb fluorescence by a partially isolated mixture of the storage proteins. Lipophorin did not quench Rb fluorescence. Rb was heat-extracted from whole hemolymph and identified by its fluorescence spectra and by reverse phase HPLC with fluorescence detection. The two subunits shared by the three holoproteins have been isolated by sequential density gradient ultracentrifugation, gel permeation HPLC, and reverse phase HPLC. All three holoproteins shared the alpha subunit (M(r) 75,000), while the beta subunit (M(r) 71,000) was lacking from one of the three. Repeated passage through an anion exchange column yielded two of the three proteins (Ib and II) in homogeneous form. Chemical crosslinking with dimethylsuberimidate indicated a hexameric structure for the holoproteins. All subunits and holoproteins stained as high mannose glycoproteins when probed with biotinylated concanavalin A on PVDF membranes. The alpha subunit was high in Met, His, and Thr, and the beta subunit was high in Lys. Both were high in Pro and had approximately 16% Phe+Tyr. Sequences of the 20 N-terminal amino acid residues of each subunit showed 45-60% homology between subunits. These coleopteran proteins also showed some sequential homology but no immunological cross-reactivity with storage proteins from the lepidopterans Galleria mellonella and Heliothis virescens. PMID- 1504323 TI - [Introduction of "Uniform requirements for manuscripts submitted to biomedical journals"]. PMID- 1504324 TI - [Attributable risk percent under an effect modifier and legal causality]. AB - Among civil trials there are cases which are influenced by evidence derived from epidemiologic studies. In such cases, causality of a factor (X) illegitimately introduced by defendants is considered to be measured with an epidemiologic measure, attributable risk percent (AR%) expressing the level of risk. This paper aims to discuss calculations and interpretations of AR% in complicated cases where plaintiffs themselves introduced an additional risk factor (Y) for the alleged health injury. When X is not an effect modifier, AR% of X adjusted for Y can be simply adopted for arriving at a judgement of causality. Where Y is an effect modifier, and is not an indispensable item in the plaintiffs' daily life (e.g., smoking), the AR% of X for those not exposed to Y and also the AR% for those exposed to Y may both need to exceed a legally determined threshold, in order for X to be legally acknowledged as being causal to the alleged injury. The role of epidemiologists for such trials is to determine the AR% of X for each level of Y, and to advise the court on a realistic range of the AR%s. PMID- 1504325 TI - [A review of studies on school-based smoking prevention programs]. AB - Research papers on school-based programs designed to prevent adolescent smoking were reviewed to determine trends in the development of smoking prevention programs as well as measures and methods of evaluation. In the USA and Europe, evaluation studies have demonstrated that the most promising smoking prevention approaches are those that focus primary attention on the psychosocial factors promoting smoking initiation. In Japan, however, most programs have shown little success. The following recommendations are made for improving the methods for evaluating program effectiveness and the future of research orientation of educational program on adolescent smoking. 1) Refinement and standardization of evaluation methods to be valid and feasible for use in studies of Japanese adolescents. 2) Improved study designs for evaluation of program effectiveness which include control groups and long term follow-up. 3) Applying smoking prevention programs which were demonstrated to be effective in the USA and Europe. 4) Development of effective cessation programs for adolescent smokers. PMID- 1504326 TI - [Effect of daily energy intake and amount of walking on body weight reduction and its maintenance]. AB - The relationship of daily energy intake and the amount of walking performed, based on pedometer readings, for effective body weight reduction were studied based on results of a weight reduction program at the Aichi Prefectural Center of Health Care from 1983 to 1990. In addition, a follow-up study based on a mailed questionnaire was performed, to further determine the relationship to maintenance of body weight reduction of energy intake and amount of walking after the conclusion of program. The subjects were two-hundred and forty middle-aged obese women who were placed on a 5-month weight reduction program consisting of diet (1500 kcal/day) and exercise (10000 walk steps/day). At the end of the program, the mean energy intake and the mean number of steps per day had reached target levels and the mean body weight reduction was 4.2 kg. The relationship of energy intake, and the number of steps walked at the end of program to the amount of reduction in body weight during the program was analyzed by multiple regression analysis, and the amount of walking expressed in the number of steps necessary for weight reduction were calculated for various energy intakes. A follow-up study was performed in 1988, with sixty-six women responding to the mailed questionnaire. Since the end of the program, body weight increase of 1.1 kg occurred, but body weight was still lower than initially. Although mean energy intake increased after the program, a level about 200 kcal less than at the beginning of the program was being maintained, so the effect of diet recommendation in the program appeared to be retained.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1504327 TI - [A study of the relationship between job type and/or position to life style and health of male white-collar workers]. AB - The relationship between the type of job and/or position of male white-collar workers to their working life, life style, health behavior, and health condition was examined based on data obtained from a survey of 1129 male workers in a major computer manufacturing company in 1988. The results were as follows: 1. Work, life style, health behavior, and health condition of male white-collar workers are strongly affected by type of job and position when adjusted for education, income, and age. 2. Workers in the sales department and engineering department appeared to have the most problems associated with working life, life style, health behavior, and health condition. Workers in sales, especially, displayed Type A behavior and their job was characterized by a lot of business transactions in a working environment that requires them to work until late at night. This leads to an irregular diet, late bed time, and makes their family relationships worse. Workers in the engineering department had work loads that were heavy because they have the longest working hours, and the content of their jobs is a mixture of both research and sales. Consequently their health is not good. On the other hands, workers in the laboratory had the best situation, and with general workers about average in terms of working life, life style, health behavior, and the state of health. 3. The department heads have the best conditions of life and health over all, except for their diet. The chiefs of sections are generally in the middle between the department heads and ordinary workers in terms of life and health. They drink and smoke heavily and show Type A behavior characteristics. Ordinary workers appear to have the most problems in working life, life style, health behavior, and health condition. From these results it may be concluded that this is associated with the difference in work type and position of these workers compared to managerial class and also with a low level of morale. PMID- 1504328 TI - [The rupture of cedar pollens in nasal secretions]. AB - Allergic rhinitis caused by pollen of Japanese cedar (Cryptomeria japonica) is found in Japan. These pollens, when inhaled into the nasal cavity, contact the nasal mucus membrane, and the allergens separate from the pollens, and pass through the nasal mucosa to interact with the mast cell-bound IgE. Patients with allergic rhinitis produce a great volume of nasal secretion from the mucosa. The morphological transformation of the cedar pollens when mixed with nasal secretion was studied. Nasal secretion was collected from two patients with allergic rhinitis. Cedar pollen gathered from a Japanese cedar tree was mixed with distilled water, and the cedar pollen suspension was mixed with a drop of nasal secretion on a slide glass at the room temperature (23 degrees C), and examined by phase-contrast microscopy. Of the pollen 20.6% were ruptured after 3 min, and 52.9% after 10 min, 84.9% after 40 min, and 81.3% after 60 min respectively. Further changes in shape of the ruptured pollens were observed with continued incubation. A hole opened in the cytoplasmic membrane through which the nucleus escaped, and crinkling of the residual cytoplasmic membrane was observed. The escaped nucleus separated into many small granules. In order to determine possible causes of the pollen rupture in nasal secretion, the relationship between pH of the nasal secretion and rupture rate was examined. The pH of the nasal secretion from two patients was 8.95 and 9.15 respectively. Salt solutions of 0.1 M NaCl, (NH4) 2SO4, NaNO3, CaCl2, Na2SO4, KCl, MgSO4, had pH range from 5.13 to 6.40.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1504329 TI - [Involuntary smoking in a workplace situation--discomfort of nonsmokers and interpersonal awareness of smokers]. AB - A questionnaire survey was conducted to examine the socio-behavioral interaction between smokers and nonsmokers in a workplace situation. A socio-behavioral interaction is hypothesized to be centered around the subjective discomfort such as 'bothered feelings' towards involuntary smoking among nonsmokers. Study subjects were 1,134 nonsmokers and 1,457 smokers working in 21 small-scale production companies in Japan. Among nonsmokers, a combined 93.3% reported 'perceived exposure to smoking', 'always', 'often', or 'sometimes' compared to 6.6% reporting 'never'. Similarly, 74.6% experienced 'bothered feelings' 'sometimes', 'always', or 'often' compared to 25.3% reporting 'never'. A combined total of 39.4% expressed their discomfort to smokers 'sometimes', 'often', and 'always' compared to 60.6% who 'never' did. In contrast, 59.1% of smokers responded that they smoked with consideration of nonsmokers' presence (interpersonal awareness) 'sometimes', 'often', and 'always' compared to 41.0% for 'never'. 'Bothered feelings' among nonsmokers was significantly lower among those with past smoking history and correlated positively with 'perceived exposure to smoking' (rs = 0.22, p less than 0.001) and with 'expression of discomfort among both male (rs = 0.32, p less than 0.001) and female nonsmokers (rs = 0.34, p less than 0.001). Among male smokers 'interpersonal awareness' was significantly higher for those with less cigarette consumption and with past history of smoking cessation. A regression analysis was performed using mean scores calculated for smokers and nonsmokers of each workplace. Lower 'bothered feelings' of nonsmokers significantly correlated with higher 'interpersonal awareness' of smokers (r = -0.59, p less than 0.005). These finding imply the presence of socio-behavioral interactions between smokers and nonsmokers and thus suggest the significance of workplace education on involuntary smoking. PMID- 1504330 TI - [Death education for the healthy elderly]. PMID- 1504331 TI - [Diagnosis of colon cancer--history and problems]. PMID- 1504332 TI - [Problems associated with mass-screening system for gastric cancer in Japan]. AB - In the mass-screening system for gastric cancer, subjects are primarily examined by contrasted indirect roentgenography and if secondary examination is diagnosed to be necessary, they are examined by contrasted direct roentgenography or gastric fiberscopy. Methods for increasing the efficiency of this system from the standpoint of cost-effectiveness were studied, and the basis for decision of whether or not serological examinations such as of serum pepsinogens and serum anti-Helicobacter-antibodies should be brought in to the system, and in what manner serological examinations should be brought in to the system if proven to be effective were examined. Problems found in the present practiced system and the proposed new system with serological examinations were repetition interval for examinations, selection of high-risk subjects and communication between subjects and the medical staff or among the members of the medical staff. Analysis by receiver operating characteristics curve should be included when serological examinations are indicated. In addition whether the mass-screening system for gastric cancer produces an actual reduction in death by gastric cancer should be confirmed after the system is made more efficient. PMID- 1504333 TI - [Relationship of smoking to absenteeism due to illness and injury in male workers]. AB - The relationship between smoking and absenteeism due to illness and injury was studied in 21,924 male workers employed in the chemical fiber industry in Japan. Smokers had a significantly higher incidence of absence than non-smokers. The proportion of cases of absence in smokers was 30% higher and the number of days of absence was 28% greater than in non-smokers. Ex-smokers also had a significantly higher incidence of absence than non-smokers. In ex-smokers the proportion of cases of absence was 22% higher and the number of days of absence was 68% greater than in non-smokers. Although there was no significant difference between smokers and non-smokers in the number of days of absence attributed to cardiovascular or respiratory diseases, smokers were absent for about twice as many days as non-smokers for diseases of the digestive system. For ex-smokers the number of days of absence was 4.3 times higher for cardiovascular diseases, 1.5 times higher for respiratory diseases, and 2.9 times higher for digestive system diseases than in non-smokers. After correction for age, type of work, Body Mass Index, exercise, and drinking by multiple logistic analysis significantly elevated relative risks for absence persisted both in smokers and ex-smokers vs. non-smokers at 1.4 and 1.3, respectively. Significant dose-response relationships between incidence of absence and the number of cigarettes smoked per day were observed in respiratory disease, diseases of the digestive system and all disease causes. A significant dose-response relationship between incidence of absence and smoking index was also observed for diseases of the digestive system. These findings clearly indicate that smoking by workers was associated with absence due to illness and injury, and suggest that smoking was a factor contributing to an increase in absenteeism due to illness and injury in workers. PMID- 1504334 TI - [A cross-sectional study of lipid peroxide levels (plasma TBA levels) in a mass health examination]. AB - Differences in plasma thiobarbituric acid (TBA) levels were studied by sex and age in 1,178 adults (471 males and 707 females) participating in a mass health examination conducted in a town of Kumamoto Prefecture in 1989. The relationships between plasma TBA levels and obesity, the consumption of cigarettes, alcohol, and fish, and various indices for health status derived from the data of physiological examinations were analyzed in age-groups 40-59 and 60-79 for both sexes. The prevalence of abnormal physiological findings by plasma TBA levels were further investigated. The results were as follows; 1. The highest plasma TBA levels for males were observed in the group aged 40-49, with levels gradually decreasing with age thereafter. The plasma TBA levels for females increased with age and the highest levels were obtained at age 60-69. The plasma TBA levels for males were significantly higher than for females at aged 40-49. 2. Plasma TBA levels for both sexes increased with obesity and the amount of fish consumed. 3. Plasma TBA levels in all examined groups had significant and strong positive correlations with serum total cholesterol levels and atherogenic indices, and had significant positive correlations with serum calcium and gamma-GTP levels. 4. A stepwise multiple regression analysis showed that plasma TBA levels for males were associated with serum total cholesterol, gamma-GTP, fish consumption and serum HDL-cholesterol in that order. The levels for female were associated with serum total cholesterol, body mass index, serum HDL-cholesterol and serum calcium in that order. The relationship with serum HDL-cholesterol was a negative correlation. 5. Prevalence of abnormal values of serum total cholesterol, atherogenic index and body mass index were significantly higher in the high plasma TBA level group than in the group with median-plasma TBA level. These results suggest that plasma TBA levels may be useful as an index of undesirable lipid metabolism. Further studies should be performed to establish the significance of the relation of plasma TBA levels to fish consumption. PMID- 1504335 TI - [A nested case-control study of risk factors for intracerebral hemorrhage and cerebral infarction classified by computed tomographic findings]. AB - Risk factors for intracerebral hemorrhage (ICH) and cerebral infarction (CI), were studied by a prospective study of 7,390 men and women aged 40-69 without a history of stroke living in three rural populations in Japan. Baseline examinations were done for populations in Akita-Ikawa and Akita-Ishizawa in 1975 1979, and for Ibaraki-Kyowa in 1981-1987, and followed until 1989 for Akita-Ikawa and Ibaraki-Kyowa and 1987 Akita-Ishizawa. There were 246 stroke cases diagnosed by clinical criteria during the follow-up period in which 74 percent (n = 181) had data from computed tomography (CT) performed within three weeks of the onset. According to these CT-findings, 181 stroke were classified as 48 with ICH, 50 with CI in penetrating artery regions (penetrating artery infarction), 33 with CI in cortical artery regions (cortical artery infarction), and 31 with subarachnoid hemorrhage while there were 19 with stroke without any evident CT abnormality. Cortical artery infarction was further classified as embolic type (n = 17) and thrombotic type (n = 9) according to clinical findings of the onset and presence of possible embolic sources such as atrial fibrillation, congenital heart disease, myocardial infarction and heart valve diseases. Using a nested case control design, risk variables at baseline examination were compared between 131 stroke cases, 48 ICH and 83 CI, with 655 controls matched for sex, age (+/- 3), and the follow-up year. Univariate analysis showed that high blood pressure was associated with all types of stroke. From conditional logistic regression analysis significant risk variables were found to be high blood pressure for ICH and penetrating artery infarction, while atrial fibrillation and ST-T abnormality in electrocardiogram (ECG) were risk variables for cortical artery infarction. Associations with hypertensive or arteriosclerotic changes in ocular fundus were stronger for penetrating artery infarction than ICH and cortical artery infarction. ST-T abnormality in ECG was associated with embolic type cortical artery infarction and high blood pressure was associated with the thrombotic type, although the number of cases were small. Compared to controls, cortical artery infarction showed a higher mean value of serum total cholesterol for thrombotic type cortical infarction, and lower mean values for embolic type and ICH, but none of them reached statistical significance. The present study also suggests that duration of hypertension varied with type of stroke. ICH may develop due to acute effects of hypertension, while penetrating artery infarction and cortical artery infarction develop by chronic effects of hypertension. PMID- 1504336 TI - [Differences in the prevalences of Raynaud's phenomenon in general populations living in a mountain area and in a plain area]. AB - Raynaud's phenomenon (RP) which is the episodic and reversible vascular spasm of the extremities can be elicited by cold or emotional changes. RP has been classified into two groups. One is primary Raynaud's phenomenon (PRP) with no identifiable underlying disease and/or cause, and the other is the secondary form of RP (Raynaud's syndrome) with underlying disease and/or cause, e.g., collagen disease, trauma, vibration from vibrating tools, etc. In the present study using this definition of RP the prevalences of RP were studied in general populations in a mountain village "T" and in a town "K" located in a plain area in Gifu prefecture, Japan. The prevalences of RP in T Village were 8.0% (25/314) in males and 3.5% (16/454) in females, and in K Town 2.7% (7/259) in males and 3.2% (21/657) in females. In 52% of the male cases in T Village it was estimated that the exposure to vibration from vibrating tools was the cause of RP. In K Town no male cases of RP were induced by vibration. Exposure to vibration may be one of the important factors when prevalences of RP are investigated in various areas. There were no significant differences between the two areas in the prevalences of PRP (T Village: male 2.9%, female 3.1%; K Town: male 2.7%, female 2.9%). The annual mean air temperature was usually 5-6 degrees C lower in T Village than that in K Town. From the results of this study the differences in the mean air temperature did not appear to have a significant influence on the prevalence of PRP in each area. PMID- 1504337 TI - [Effects of food intake, dietary habits and life style on health status as determined by clinical blood tests of adult men]. AB - A survey of the frequency of various kinds of foods, dietary habits, life style, and health status was performed on 2,049 men aged from 40 to 59 living in an urban area who were participants in a "human dock" medical checkup. The relationships between these factors and health status were studied in order to identify a particular life style associated with good health status. The instrument utilized in this survey was a special form of a structured questionnaire. The results are summarized below. 1. The frequency of various kinds of foods were correlated with the kind of breakfast eaten, dietary habits, physical exercise habits, daily physical activity, smoking, and occupation. The strongest correlation to frequency of various kinds of foods was found to be with the kind of breakfast eaten and dietary habits. 2. Dietary habits were also correlated to various aspects of life style: smoking, drinking, the frequency of various kinds of foods, kind of breakfast eaten, daily physical activity, sleeping hours, habits related to physical exercise, and the frequency of meals eaten away from home. Dietary habits correlated most closely with the frequency of various kinds of foods and daily physical activity. The frequency of various kinds of food and dietary habits were found to correlate with various aspects of life style, and those subjects with good overall life styles were also found to have desirable dietary life styles. The correlation of desirable dietary habits, food intake and a suitable life style with good health status was confirmed by the results of clinical blood tests used as an index of health status.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1504338 TI - Peptide sequencing by matrix-assisted laser-desorption mass spectrometry. AB - A novel method of peptide sequencing by mass spectrometry is described. Metastable decay of laser-desorbed ions, taking place in the first field-free drift region of a reflection time-of-flight mass spectrometer, has been monitored to get structural information from larger peptides. Fragment ions from metastable decay are mass analysed by adjusting the potentials of the ion reflectron according to the kinetic energies of the ions. The features of the technique and its significance for future applications are outlined. PMID- 1504339 TI - Determination of the acyl moieties of the antibiotic complex A40926 and their relation with the membrane lipids of the producer strain. AB - Structures of the fatty acid residues characterizing the various components of A40926 were determined by gas chromatography/mass spectrometry on the methyl esters obtained by methanolysis of the complex. The results confirm the residues previously assigned to Factor A (n-undecanoic acid) and B (10-methyl-undecanoic acid) and establish the residues of Factor A1 (9-methyl-decanoic acid), B1 (n dodecanoic acid), RS1 (8-methyl-nonanoic acid), RS2 (n-decanoic acid), and RS3 (n tridecanoic acid). As the Actinomadura species contain in their mycelia large quantities of C15-C17 fatty acid residues as membrane phospholipids, these mycelia were saponified and the fatty acids obtained were analyzed as above. There is a close correlation between the fatty acid content of A40926 complex and that of the longer homologues in the producer mycelia. PMID- 1504340 TI - Ionspray mass spectrometry of marine toxins. IV. Determination of diarrhetic shellfish poisoning toxins in mussel tissue by liquid chromatography/mass spectrometry. AB - An improved liquid chromatographic/mass spectrometric (LC/MS) method utilizing gradient elution and ion-spray ionization is described for the sensitive determination of okadaic acid and dinophysistoxin-1, the principal toxins implicated in cases of diarrhetic shellfish poisoning. The method was used to confirm the presence of both toxins, together with a recently identified isomer of okadaic acid, dinophysistoxin-2, in various samples of cultivated blue mussels (Mytilus edulis) from Canadian and European waters. The method provided a mass detection limit of 0.4 ng for each toxin, thus allowing detection of 40 ng per g of whole mussel tissue (or approximately 10 ng/g if only the digestive glands were used in the assay). Quantitative results obtained by LC/MS were in good agreement with those obtained by derivatization and high-performance liquid chromatography with fluorescence detection. PMID- 1504341 TI - Analysis of saxitoxin in urine by continuous-flow fast-atom bombardment mass spectrometry. AB - An improved method of saxitoxin analysis in urine using continuous-flow fast-atom bombardment mass spectrometry was developed. Parameters studied were matrix composition, matrix flow, temperature of probe tip, probe-tip design and sample extraction. Optimal detection was obtained using the following matrix composition: 5% glycerol, 0.5% acetic acid, 0.025% sodium dodecylsulfate, 0.1% polyethylene glycol (PEG) 400 and 0.5% PEG 300; probe-tip temperature: (approximately 55 degrees C); flow rate: 5 or 8 microL per min.; probe tip: Olson Hogge design. The STX standard was detected at 200 pg with signal-to-noise ratio of 11. The percent recovery of saxitoxin from human urine after clean-up on a weak cation exchange column was 75%. PMID- 1504342 TI - Secondary-ion and electron production from surfaces bombarded by large polyatomic ions. AB - Heavy molecular ions with energies in the range 10-20 keV and masses from 276 u to 132,000 u, produced by matrix-assisted laser desorption, were used as primary projectiles to produce secondary-ion spectra from a variety of surfaces in a tandem time-of-flight mass spectrometer. In the negative mode the ratio of electron emission to secondary-ion emission was found to decrease rapidly with increasing projectile mass. Ion emission was found to dominate for primary ions larger than approximately 10,000 u. Positive or negative molecular ions and cations were observed from several organic targets of masses up to 1140 u (gramicidin S) for incident projectiles up to mass 132,000 u, i.e., for projectile speeds down to approximately 7000 m/s. Other ions characteristic of the target were also observed for these projectiles. Thus, large polyatomic ions can cause secondary-ion desorption even at very low velocity. The background ions of both polarities are similar to those found in keV particle bombardment by monatomic projectiles. The same ions are observed for all the projectiles; most can be identified with hydrocarbon background. The relative intensities of the background positive ions are largely independent of projectile, and for both polarities the ratio of the ions characterizing the target to those forming the background is approximately constant for all the projectiles. These results strongly suggest that the background ions come from the usual layer of organic impurities attached to the target surface. No direct evidence for surface-induced dissociation was observed in this mass and energy range. PMID- 1504343 TI - Mass spectrometer systems and products. An expanded directory of manufacturers and suppliers. PMID- 1504344 TI - Fragmentation studies of peptides: the formation of y ions. AB - The mechanism for the formation of y ions in the collision-induced dissociation (CID) spectra of protonated peptides produced by fast-atom bombardment was investigated by tandem mass spectrometry and deuterium labelling studies. The results show that a hydrogen atom attached to nitrogen and not to carbon migrates during cleavage of the amide bond. A mechanism based on these results is presented. PMID- 1504345 TI - Preservation and visualization of molecular structure in detergent-extracted whole mounts of cultured cells. AB - Today's electron microscopes have a resolution sufficient to resolve supramolecular structures. However, the methods used to prepare biological samples for electron microscopy often limit our ability to achieve the resolution that is theoretically possible. We use whole mounts of detergent-extracted cells grown on Formvar-coated gold grids as a model system to evaluate various steps in the preparation of biological samples for high resolution scanning electron microscopy (SEM). Factors that are important in determining the structure and composition of detergent-extracted cells include the nature of the detergent and the composition of the extraction vehicle. Chelation of calcium is extremely important to stabilize and preserve the cytoskeletal filaments. We have also demonstrated both morphologically and by gel electrophoresis that treatment of cells with bifunctional protein crosslinkers before or during extraction with detergent can significantly enhance the preservation of both proteins and supramolecular structures. The methods used to dry samples are a major determinant of the quality of structural preservation. For cytoskeletons freeze drying (FD) is superior to critical point-drying (CPD), one reason being that CPD samples have to be dehydrated, thereby causing more shrinkage as compared to FD samples. The high pressures to which samples are exposed during CPD may also cause increased shrinkage, and water contamination during CPD causes severe structural damage. We have obtained the best structural preservation of detergent extracted and fixed cells by manually plunging them into liquid propane and drying over night in a freeze-dryer. The factor that most limits achievement of high resolution in SEM is the metal coat, which has to be very thin, uniform, and free of grain in order not to hide structures or to create artifactual ones. We have found that sputter-coating with 1-3 nm of tungsten (W) or niobium (Nb) gives extremely fine-grained films as well as satisfactory emission of secondary electrons. These samples can also be examined at high resolution by transmission electron microscopy (TEM) and scanning transmission electron microscopy (STEM). The best preservation and visualization of supramolecular structures have been obtained using cryosputtering, in which the samples are freeze-dried and then sputter-coated within the freeze-dryer while still frozen. PMID- 1504346 TI - Sample preparation for electron microscopy of internal cell structure. AB - Methods are reviewed for examination of internal cell structure by high resolution scanning electron microscopy and compared with the rapid-freeze deep etch replica technique used in transmission electron microscopy. Rapid freezing of fresh material, followed by freeze-fracture, provides a theoretically attractive approach in ultrastructure studies, but the high protein and solute content of most cells prevents a deep three-dimensional view for material frozen without some form of extraction. After discussion of other methods it is concluded that the most useful general approach, at least for cultured cells, is to first permeabilize or break open the cells in a medium which preserves the structure under study in a functional state as, for example, the movement of chromosomes along the division spindle, or transport of proteins within the Golgi region. After permeabilization, with attendant partial extraction, the preparation can be fixed, then viewed by either deep-etch replication, or by high resolution scanning electron microscopy, with structure of interest revealed in deep view. PMID- 1504347 TI - Ultrastructural imaging of freeze-fractured plant cells in the scanning electron microscope. AB - The application of the freeze-fracture and cytoplasmic maceration technique in ultrastructural studies of plant cells is described. A major advantage of the technique is, that by extracting mobile cytoplasmic components from the freeze fractured cells, surface relief is introduced and three-dimensional information is obtainable. The details of specimen preparation are described and the results obtained are reviewed. The use of chitosan embedding for very small or fragile specimens is described. PMID- 1504348 TI - Freeze-substitution of chemically stabilized samples for biological field emission scanning electron microscopy. AB - The high resolution imaging capabilities of modern field emission scanning electron microscopes require adequately improved tissue preparation procedures to prevent the collapse of macromolecular structures and the extraction of molecules. A routine cryo-stabilization technique is described which utilizes chemical crosslinking and cryo-dehydration for mechanical and chemical stabilization of protein and lipid structures and increase of electrical conductivity of the sample. Thiocarbohydrazide (TCH) serves as a general mordant for osmium tetroxide crosslinking. However, extensive washing after all impregnation steps is necessary to dissolve unspecific osmium black precipitations at the sample surface. Collagen I aggregates showed increased stability against collapse after TCH osmification alone, whereas pulmonary surfactant liposomes require additional freeze-substitution in methanol and Freon 113 for stabilization during critical point drying. Environmental scanning electron microscopy (at water vapor pressures of 5-10 torr within the specimen chamber) was used to control, in the wet phase, the stabilization procedure at the level of chemical crosslinkage. It could be confirmed that tannic acid, often used to stabilize lipids, leads to artificial rearrangement of bilayered liposomes into compact presumable multilayered bodies, whereas the TCH osmification preserved liposome structures and their aggregates. The increase of electrical conductivity of sliced tissue was demonstrated on kidney. Support technologies for the cryo-stabilization procedures are described in detail, as well as simple routines for first stabilization trials with new samples. On pulmonary tissue, the excellent preservation of alveolar shape and fine structures of intermediate forms of surfactant are described. PMID- 1504349 TI - Chemical extraction of the cytosol using osmium tetroxide for high resolution scanning electron microscopy. AB - Detailed examination of subcellular structures in three dimensions (3D) by high resolution scanning electron microscopy (HRSEM) is now possible due to improvements in the design of the scanning electron microscope and the introduction of methods of specimen preparation using chemical removal of the cytosol and cytoskeleton by dilute osmium tetroxide. Cells which have been fixed, frozen, cleaved, thawed, and subjected to cytosol extraction display intact intracellular structures in 3D including nuclear chromatin, endoplasmic reticulum, mitochondria, and the Golgi complex at a resolution close to that of conventional biological transmission electron microscopy (TEM). Small changes in the 3D structure of subcellular components can be conveniently examined in this way in development, in a variety of physiological processes and in disease. Broad areas of the specimen can be quickly surveyed by HRSEM since sectioning is not required and specimens of comparatively large size (up to 5 mm3) can be placed in the microscope. Extraction of the cytosol with dilute osmium tetroxide (OsO4) exposes subcellular structures in relief, permitting their examination in 3D from several aspects. However, the OsO4 extraction technique is limited, since significant intracellular structures, such as the cytoskeleton, vesicles, and antibody binding sites can be removed or inactivated during the cytosol removal steps. PMID- 1504350 TI - Determination of conditions for optimum resolution of a high angle thin window energy dispersive spectrometer. AB - The energy resolution of an energy dispersive spectrometer (EDS) equipped with an ultrathin window (UTW) and mounted at a high take-off angle (72 degrees) on a transmission electron microscope has been studied under a variety of operating conditions. The spectrometer resolution is close to that specified by the manufacturer, up to count rates of 400 cps. Above 400 cps the resolution deteriorates rapidly, and the MCA dead time and zero width increase. Above 10 keV, the height of the background is much greater than expected for bremsstrahlung and shows the shape which has previously been attributed to backscattered electron flux into the detector. It is postulated that the deterioration in resolution with count rate is caused by backscattered electrons reaching the detector through the UTW. PMID- 1504351 TI - Comparative study of ion milling techniques in cross-sectional transmission electron microscope specimen preparation. PMID- 1504352 TI - Preparation of aqueous standards for low temperature X-ray microanalysis. AB - A technique, using Nuclepore polycarbonate membrane filters as a containing medium for very small volumes of ionic standard solutions, to produce homogeneous ice standards is described. The standards are suitable for use in a scanning electron microscope. The relationship between elemental X-ray counts and ionic concentration is found to be linear. The method is rapid and simple. Minimum detectable concentrations are given. PMID- 1504353 TI - Ultrastructural studies on membrane, cytoskeletal, mucous, and protective compartments in olfaction. AB - There is a great variety in the morphological appearance of olfactory structures across the metazoan animal kingdom. Despite this variety the receptive structures themselves have a strikingly similar architecture, namely some type of elongated cellular extension that is spanned by a membrane and surrounded by mucus. These cellular extensions can either be modified primary or secondary cilia, or microvilli. There are more similarities between membranes of these extensions than between the cytoskeletal elements immediately underneath the membranes. One might infer that the cytoskeletal elements of the cellular extensions merely serve as a scaffold for the membranes, whereas the similarity in membrane ultrastructure provides morphological evidence supporting the concept that these membranes are responsible for the initial olfactory transduction process. The transduced message is transported to the brain, where it is decoded to initiate the cascade of events resulting in the organisms' appropriate behavioral response to the initial odorous stimulus. The varying appearance of olfactory structures across the animal kingdom is probably produced by evolutionary pressure to adapt the olfactory system to the animal's environment. This review deals with the ultrastructural aspects of these facets of olfaction. PMID- 1504355 TI - Peripheral sensilla of some lower invertebrates: the Platyhelminthes and Nematoda. AB - The flatworms (Platyhelminthes) and the round worms (Nematoda) are phyla exhibiting strikingly different levels of cellular organization. In both, sensilla are composed of the endings of sensory dendrites intercalated into their epidermis. In flatworms, sensilla that penetrate the syncytial epidermis bear sensory processes derived from cilia. In free-living species, the sensory processes more closely resemble motile cilia, while in parasites, greater deviations occur from the classical cilium pattern. Estimates of the function of the various sensilla have been largely arbitrary, and remain based on ultrastructural features. Sensilla in round worms lie below or within a heavy secreted cuticle. Two glia-like cell types occur. The socket cell mediates contact with cuticle and is responsible for cuticular modifications essential for operation of the sensillum. The sheath cell forms a receptor cavity around the sensory processes and regulates its environment. Sensory processes vary greatly from the classical cilium pattern. Absence of a basal body, but preservation of a ciliary necklace, suggests that the latter has a primary importance in sensory transduction. Estimates of function are based largely on ultrastructural features and analogies to arthropod sensilla. Genetic studies with the free-living nematode Caenorhabditis are beginning to demonstrate details of function and development. Speculations on the roles of basal bodies, rootlets, and vesicles and on the significance of recessed sensilla are given. PMID- 1504354 TI - Cortical ultrastructure and chemoreception in ciliated protists (Ciliophora). AB - The ciliated protists (ciliates) offer a unique opportunity to explore the relationship between chemoreception and cell structure. Ciliates resemble chemosensory neurons in their responses to stimuli and presence of cilia. Ciliates have highly patterned surfaces that should permit precise localization of chemoreceptors in relation to effector organelles. Furthermore, ciliates are easy to grow and to manipulate genetically; they can also be readily studied biochemically and by electrophysiological techniques. This review contains a comparative description of the ultrastructural features of the ciliate cell surface relevant to chemoreception, examines the structural features of putative chemoreceptive cilia, and provides a summary of the electron microscopic information available so far bearing on chemoreceptive aspects of swimming, feeding, excretion, endocytosis, and sexual responses of ciliates. The electron microscopic identification and localization of specific chemoreceptive macromolecules and organelles at the molecular level have not yet been achieved in ciliates. These await the development of specific probes for chemoreceptor and transduction macromolecules. Nevertheless, the electron microscope has provided a wealth of information about the surface features of ciliates where chemoreception is believed to take place. Such morphological information will prove essential to a complete understanding of reception and transduction at the molecular level. In the ciliates, major questions to be answered relate to the apportionment of chemoreceptive functions between the cilia and cell soma, the global distribution of receptors in relation to the anterior-posterior, dorsal-ventral, and left right axes of the cell, and the relationship of receptors to ultrastructural components of the cell coat, cell membrane, and cytoskeleton. PMID- 1504356 TI - Preparation of TEM foils from Nb-10 a/o Si. AB - Ductile phase toughened composites contain phases with significantly different physical properties. Consequently, these phases thin at different rates depending on the sample preparation procedure. A new TEM foil preparation method for the ductile phase toughened Nb-10 a/o Si material has been developed. The method involves chemical thinning in a 70% nitric acid/30% hydrofluoric acid solution followed by electropolishing in a 12.5% sulfuric acid/87.5% methanol electrolyte at -40 degrees C. This procedure for making TEM foils results in large thin areas with the minimum of artifacts. Mechanical grinding of a sample followed by either ion milling, dimpling, or electropolishing produced foils with large electron transparent areas, but with uncharacteristic features of the original Nb-10 a/o Si alloy microstructure. These artifacts were identified as dislocations, surface mottling, and antiphase domains. PMID- 1504357 TI - In situ freeze-fracture of monolayer cell cultures grown on a permeable support. AB - The growth of cultured epithelial cells on permeable supports allows increased cell differentiation and the assessment of a variety of transcellular and paracellular transport processes. The need to assess the corresponding ultrastructural characteristics of these cells under identical conditions prompted this laboratory to develop a reliable method for producing freeze fracture replicas of these cultures. Sections of filter inserts with the cell side facing up are placed between layers of polyvinyl alcohol with a strip of mylar positioned on the layer of polyvinyl alcohol. Following freezing, the monolayer is fractured by lifting the mylar strip from the assembly. The result is a consistent fracture of the apical membrane sufficient for analysis of tight junction sealing strands, microvilli distribution, and intramembranous particle (IMP) distribution between apical and lateral membrane domains. This method utilizes standard equipment and readily available materials and, most importantly, allows the freeze-fracture and replication of an undisturbed cell monolayer. PMID- 1504358 TI - A method for rapidly collecting serial sections for light microscopy. PMID- 1504360 TI - The language of epidemiology (XII.): Meta-analysis, studying studies. PMID- 1504359 TI - Gauging the fevered brow. PMID- 1504361 TI - Colorectal carcinoma in Rhode Island: clinical experience with 841 cases. PMID- 1504362 TI - Immune neutropenia and pregnancy. PMID- 1504363 TI - Transfer from animal to human insulin: a clinical experience. PMID- 1504364 TI - Radon: health implications in Rhode Island. PMID- 1504365 TI - Decline in cigarette smoking among Rhode Island women. PMID- 1504366 TI - Impartial medical evaluation. PMID- 1504367 TI - Role for the submandibular gland in modulating pulmonary inflammation following induction of systemic anaphylaxis. AB - Previous studies have shown that bilateral decentralization of the superior cervical ganglia (SCG; decentralization) attenuates allergen-induced pulmonary inflammatory responses in male rats sensitized to the nematode Nippostrongylus brasiliensis. The present report examines the neuronal and glandular mechanisms mediating the protection against pulmonary inflammation afforded by decentralization. Tissues and organs innervated by the SCG are responsible for this protection since, in a manner similar to decentralization, bilateral removal of the SCG (ganglionectomy) reduced anaphylaxis-induced accumulation of inflammatory cells in bronchoalveolar lavage fluid. Removal of the submandibular gland (sialadenectomy) did not modify the severity of the pulmonary inflammation, but concurrent sialadenectomy and decentralization abolished the protective effect of decentralization. Thus, we postulate that cervical sympathetic nerves tonically inhibit release of anti-inflammatory factors from submandibular glands. No relationship was found between noradrenaline and serotonin content of submandibular glands and the degree of protection against pulmonary inflammation offered by decentralization and ganglionectomy. Both decentralization and ganglionectomy appeared to increase the level of transcripts that encode immunomodulatory growth factors (nerve growth factor and epidermal growth factor) in submandibular glands, but these denervations evidently did not modify the transcripts for TGF beta 2. Systemic inflammatory events are regulated by the central nervous system at a level superior to the SCG probably through modulation of immunoregulatory factors in submandibular glands. PMID- 1504368 TI - Modulation of human natural killer cell activity by exposure to uncontrollable stress. AB - Changes in natural killer cell (NK) activity and proportions of circulating T and NK lymphocyte subsets were assessed in adult males immediately after exposure to controllable or uncontrollable stress (noise) as well as 24 and 72 h later, in order to track the time course of the effects of stress. The role of control relevant personality variables as moderators of the stress-immunosuppression relationship was considered. Subjects who perceived they had control over the noise as well as no-noise "control" subjects showed no reduction in NK activity. By contrast, subjects who perceived that they had no control over the stressor showed reduced NK activity immediately after the conclusion of the first 20-min stress session, and the reduced NK activity was found as long as 72 h later. Optimism and one's desire to be in control enhanced the negative impact of uncontrollable noise on NK activity. No differences between conditions were found on number of NK cells or a variety of T cell subsets. The results suggest the importance of perceived control in moderating the short- and long-term effects of stress on NK activity. PMID- 1504369 TI - Neuro-hormonal host defence in endotoxin shock. AB - The sensitivity (LD100) of mice to lipopolysaccharide (LPS) endotoxin and to its toxic moiety, lipid A (LA), increased 500-fold after adrenalectomy (ADX). Inhibition of glucocorticoid synthesis in intact mice by metyrapone had a similar, though less dramatic, sensitizing effect to LPS. In ADX mice, the serum level of tumor necrosis factor-alpha (TNF) was 40-60 times higher than that in controls at 2 h after LPS/LA treatment. In intact mice the serum corticosterone level fell 1 h after lipid A injection to below detectable levels, which was followed by a brisk increase reaching the peak level of 48-50 micrograms/100 ml at 2 h. Both TNF production and the lethal effect of PLS/LA could be inhibited in ADX mice by glucocorticoid treatment. Plasma prolactin was increased significantly 1 h after endotoxin administration in both intact and ADX animals. PMID- 1504370 TI - Stress-induced alterations in interferon production and class II histocompatibility antigen expression. AB - Mild electric foot-shock has been shown to be a stressor that can alter immune responses. Male Lewis rats were exposed to one session of 16 5.0-s 1.6-mA foot shocks. Production of interferon-gamma by splenocytes in response to concanavalin A was decreased in spleens from the shocked rats compared to control spleens. Spleen cells from rats treated with nadolol, a peripherally acting beta adrenergic receptor antagonist, and then shocked, showed dose-dependent attenuation of the suppression of interferon-gamma production. This suggests that catecholamines mediate shock-induced suppression of interferon-gamma production. The percentage of splenic mononuclear cells expressing class II histocompatibility (Ia) antigens on their surfaces from spleens of shocked rats was determined by flow cytometry. Significantly decreased class II positive mononuclear cells were present in the spleens of shocked rats in comparison to the spleens of control rats. This may reflect an alteration of cell trafficking or decreased production of class II antigens. PMID- 1504371 TI - Removal from natal social group to peer housing affects cortisol levels and absolute numbers of T cell subsets in juvenile rhesus monkeys. AB - Psychosocial stress associated with the removal of six naive juvenile rhesus monkeys from their natal social group to peer housing resulted in increased basal cortisol secretion and significant decrements in the absolute numbers of the T lymphocyte subsets in the peripheral blood. Six subjects matched for age and social rank remained in the group of 80 animals serving as controls. Baseline immune and cortisol measurements were obtained before the six test subjects were removed from the group and housed together in an outdoor circular enclosure. Blood samples were taken 24 h following removal of the test subjects from the group and at intervals thereafter through 11 weeks. Compared to controls, test subjects showed a significant decrease in the absolute numbers of CD4+ (-56.9%) and CD8+ T cells (-57.6%) and a significant increase in basal cortisol levels (+43.9%) 24 h following removal to peer housing. Group difference in the absolute numbers of most immune cells persisted through 11 weeks, whereas cortisol differences lasted only through 2 weeks. These data, when compared to an earlier study employing an identical protocol, with the exception that subjects were housed in indoor individual cages following separation, fail to demonstrate a modulating effect of randomly chosen peer-mates on the stress effects produced by social separation. PMID- 1504372 TI - Central nervous system influences on lymphocyte migration. AB - The immune response network is only one of many physiologic adaptive responses to environmental change and there is now substantial evidence that adaptive responses involving the central nervous system have an impact on immune outcome. Effective immune function depends upon a highly mobile population of precursor and effector cells of the lymphoid system. In this review it is proposed that many of the alterations in immunity resulting from CNS activity may be explained in terms of changes in lymphocyte migration patterns in response to endocrine signals, neural signals via neurotransmitter release, or direct contacts between nerves and cells of the immune system. PMID- 1504373 TI - What differentiates antiestrogen-liganded vs estradiol-liganded estrogen receptor action? AB - This paper provides an annotated summary of the current literature detailing what is known about the interaction of antiestrogen-liganded estrogen receptor (ER) vs estradiol-liganded ER with DNA in vitro and in vivo. It describes the current models of the mechanism by which antiestrogen-liganded ER blocks transcription of certain estrogen-regulated genes. PMID- 1504374 TI - Gene amplification as a target for cancer chemotherapy. AB - Facile gene amplification is one aspect of the genetic instability associated with transformed cells. Amplification of oncogenes and proto-oncogenes contributes to carcinogenesis and tumor progression. Gene amplification is also a common basis for resistance to anticancer drugs. The observation that low level cytotoxic stress can cause rapid loss of amplified genes from cultured cell populations suggests that gene amplification may be a potential target for cancer chemotherapy. Drug-induced loss of amplified genes is seen with a wide variety of extrachromosomally amplified genes, including drug resistance genes and proto oncogenes. A number of drugs and differentiating agents have been reported to cause rapid loss of unstably amplified genes. An effect on amplified genes or cells carrying amplified genes may contribute to the selective action of drugs presently used for cancer chemotherapy. A better understanding of drug-induced amplified gene loss may lead to new strategies for cancer treatment. PMID- 1504375 TI - Effect of 2',2'-difluorodeoxycytidine on the viability and radiosensitivity of EMT6 cells in vitro. AB - EMT6 mouse mammary tumor cells were used to examine the cytotoxic effects of 2',2'-difluorodeoxycytidine (gemcitabine; dFdC) alone and in combination with radiation. The cytotoxicity of dFdC differed from that of most antimetabolites. The concentration-response curve for exponentially growing cells treated for 4 hr with various drug concentrations was exponential down to a surviving fraction of 0.05; thus, dFdC appeared to kill cells in all phases of the cell cycle, rather than killing only the S-phase cells that compose approximately 50% of the cell population. High concentrations of dFdC were toxic to cells in plateau phase EMT6 cultures, as well as to cells in rapidly proliferating cultures. These findings are thought to reflect the unusual cellular pharmacokinetics of the compound. Treatment of exponentially growing cultures with dFdC before, during, and after irradiation was extremely effective in killing the cells; the survival curves for cells treated with drug plus radiation were statistically compatible with either additive cytotoxicity or a synergistic effect (i.e., radiosensitization by dFdC). These studies also provided evidence that dFdC released by dying cells could produce delayed cytotoxic effects on cells not treated directly with dFdC. These data provide several bases for expecting beneficial therapeutic effects from antineoplastic regimens combining dFdC plus radiation. PMID- 1504377 TI - 5-hexyl-2'-deoxyuridine inhibition of nucleoside transport in L1210 cells. AB - Previous studies have shown that 5-hexyl-2'-deoxyuridine (HdUrd) blocked the cytotoxic effects of 5-fluorodeoxyuridine and deoxyadenosine in L1210 cells. HdUrd had no effect in preventing the inhibitory effects of 5-fluorouracil. These data suggested that HdUrd was an inhibitor of nucleoside transport in L1210 cells (Cory, J. G.; Halley, M. C.; Janey, A.; Lapis, K. Cancer Res. 50:4552-4556; 1990). Studies have now been carried out which show that HdUrd inhibits nucleoside transport as measured by [3H]uridine or [3H]formycin B transport into L1210 cells in culture. The IC50 for HdUrd inhibition of total [3H]uridine uptake was approximately 20 microM in wild-type L1210 cells. Since wild-type L1210 cells have three distinct nucleoside transporters, the effect of HdUrd on each transporter was examined using the non-metabolized nucleoside analog, formycin B. The nitrobenzylmercaptopurine riboside (NBMPR)-sensitive transporter, es, was most sensitive to HdUrd with an IC50 of 1.0 +/- 0.1 microM; the NBMPR-insensitive transporter, ei, was much less sensitive to HdUrd with an IC50 of 32 +/- 2 microM; the sodium ion-dependent transporter, cif, was the least sensitive transporter to HdUrd with an IC50 of 130 +/- 5 microM. These data support the concept that HdUrd, a relatively non-cytotoxic agent, could be useful in increasing the potency of antitumor inhibitors directed at the de novo pathways for nucleotide synthesis through the blockage of the salvage pathways for nucleosides. PMID- 1504376 TI - Cytosine methylation and suppression of O6-methylguanine-DNA methyltransferase expression in human rhabdomyosarcoma cell lines and xenografts. AB - Human tumor cell lines that do not express O6-methylguanine-DNA methyltransferase (MGMT) in detectable quantities (Mer-) are hypersensitive to the effects of O6 guanine-alkylating agents. Because the Mer- phenotype enhances tumor response to such agents, we investigated possible mechanisms involved in regulation of MGMT expression in a panel of Mer+ and Mer- pediatric rhabdomyosarcoma xenograft and cell lines. All Mer- cell and xenograft lines lacked not only MGMT activity but also the protein and mRNA as well, suggesting that its expression is transcriptionally regulated. Transfection of Mer+ and Mer- rhabdomyosarcoma cell lines with MGMT gene promoter-CAT constructs yielded similar levels of CAT expression, indicating that Mer- cells possessed the necessary factors to support transcription. Methylation in the 5'-untranslated region of the MGMT gene was assayed by Southern analysis using methylation-sensitive restriction enzymes. Digestion with HpaII and its methylation-insensitive isoschizomer, MspI, revealed little overall correlation between methylation and MGMT expression. However, methylation in a single SmaI site at position-69 was observed in all MGMT deficient lines but not in any MGMT expressing lines. These results suggest that methylation of specific cytosines in the MGMT promoter may play a role in suppressing its expression, as well as being a potentially useful marker for the Mer- phenotype. PMID- 1504378 TI - EGF receptors in R3230AC rat mammary carcinomas: characteristics and regulation in vitro and in vivo. AB - Epidermal growth factor (EGF), at 10(-11) M and 10(-10) M, stimulated [methyl 3H]thymidine incorporation into DNA and cell growth of R3230AC mammary adenocarcinomas in primary cultures, whereas at higher concentrations (10(-9) M and 10(-8) M) EGF inhibited DNA synthesis and cell growth in vitro. To determine whether these responses were receptor-mediated, 125I-EGF binding to freshly dissociated cells and primary cultures of R3230AC cells was measured and found to be time- and temperature-dependent. Specificity of EGF binding was demonstrated by 50% displacement occurring at an EGF concentration of 0.46 nM. Using 125I-EGF concentrations from 0.05 nM to 10 nM, saturable binding sites were documented; Scatchard analysis of these data produced curvilinear plots, suggesting the presence of high affinity (0.44-0.93 nM) and low affinity (1.5-4.8 nM) sites. 125I-EGF was rapidly internalized by cultured R3230AC tumor cells. By 30 min, 73% (25 degrees C) and 77% (37 degrees C) of total 125I-EGF was internalized (resistance to acid/salt extraction), whereas at 4 degrees C, cells internalized only 20% of EGF over a 3 hr incubation period. Following incubation with 125I-EGF for 2 hr at 4 degrees C, 25 degrees C, or 37 degrees C, the majority of cell associated radioactivity eluted with intact 125I-EGF. However, when the material that dissociated from R3230AC cells after the 2 hr incubation was analyzed, 38% (25 degrees C) and 46% (37 degrees C) of the radioactivity migrated as lower molecular weight products, indicating that 125I-EGF was partially degraded intracellularly by R3230AC cells in primary culture. Pre-incubation of cells in primary culture with EGF (1-100 nM) for 30 min at 37 degrees C, led to "down regulation" of EGF receptors; 1 nM EGF reduced the specific binding of 125I-EGF by 54% with higher concentrations (10 nM and 100 nM) reducing it further. Scatchard analysis of down-regulated cells showed a reduced number of high affinity binding sites with no change in the Kd of binding. Sialoadenectomy of rats had no effect on R3230AC tumor growth or EGF receptor levels in the tumor, liver, or uterus. Experiments to determine whether perturbations of the insulin milieu or ovariectomy would alter EGF receptors were performed. 125I-EGF binding was significantly elevated in tumors from diabetic rats (152% increase vs controls) and binding was returned to control (77% of intact rats) levels after administration of insulin to diabetic rats.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1504380 TI - Reference listing in cancer research. PMID- 1504379 TI - Bone marrow matrix promotes differentiation and prolongs the cell cycle of U-937 cells. AB - The extracellular matrix influences the growth and differentiation of a variety of cell types. In this study, the effects of bone marrow extracellular matrix on U-937 cells, a human histiocytic lymphoma cell line, were assessed. Sixty percent of U-937 cells adhered to extracellular matrix, whereas only 1% adhered to uncoated plastic. U-937 cells grown on extracellular matrix released significantly more lysozyme into the medium (8.3 +/- 0.3 micrograms/10(6) cells) compared to those grown on plastic (4.2 +/- 0.5 micrograms/10(6) cells). FMLP (f met-leu-phe) receptor expression was also enhanced suggesting a more mature phenotype in cells grown on matrix (2980 cpm/10(6) cells vs 230 cpm/10(6) cells on plastic). Furthermore, bone marrow extracellular matrix inhibited proliferation of U-937 cells. After four days in culture, there was a 65% inhibition of cell growth in matrix-coated flasks compared to uncoated flasks. Since an arrest in G0/G1 usually precedes mammalian cell differentiation, DNA histograms were performed on U-937 cells grown on matrix to detect such an arrest. However, the cell cycle distribution of U-937 cells grown on extracellular matrix or uncoated plastic for various time periods was similar. In contrast, bromodeoxyuridine pulse labeling revealed approximately a 5 hr prolongation in cycle length in cells grown on extracellular matrix. We conclude that bone marrow extracellular matrix induced macrophage-like differentiation and inhibited proliferation of U-937 cells with a prolongation of the cell cycle that was not G0/G1 phase specific. PMID- 1504381 TI - Pharmaceutical education--a matter of degree. PMID- 1504382 TI - Revisiting some factors contributing to variability. PMID- 1504383 TI - Medication assistance: the development of drug surveillance and drug information in The Netherlands. AB - OBJECTIVE: To describe the development of drug surveillance and drug information in The Netherlands. DATA SYNTHESIS: Historically, the professions of medicine and pharmacy have existed separately with little contact between them. Since the 1960s, this situation has changed in The Netherlands. Both professions are cooperating to an ever-increasing degree, primarily in the areas of computerized drug surveillance and individualized patient drug information, resulting in greater patient benefit. CONCLUSIONS: Exchange of knowledge between physicians and pharmacists, greater cooperation among professionals, use of computerized patient medical records, and involvement of the patient in his own healthcare will have a positive influence on the development of drug assistance in the future. PMID- 1504384 TI - Contribution to the issue of essential drugs in Czechoslovakia. AB - OBJECTIVE: To determine the ratio represented by essential drugs (EDs) in the total consumption of drugs in Czechoslovakia in 1989. DESIGN: Retrospective analysis of the assortment and consumption of EDs in 1989. SETTING: Department of the Organization and Management of Pharmacy, Faculty of Pharmacy, Bratislava. MAIN OUTCOME MEASURES: Consumption of drugs and/or pharmacotherapeutic groups, expressed by the number of formulations, number of units, and in financial terms. RESULTS: EDs constitute approximately one-third of the total consumption of drugs in Czechoslovakia (both in terms of volume and finances); almost 60 percent of EDs have dosage forms and concentrations identical to those shown in the World Health Organization Model List of Essential Drugs (Sixth List). CONCLUSIONS: The results obtained indicate that there is need for a regular updating of the drug policy within the public health branch of the government to more effectively regulate the production and import of drugs. PMID- 1504385 TI - Sucralfate-warfarin interaction. PMID- 1504386 TI - Thiethylperazine treatment of gastroparesis diabeticorum. PMID- 1504387 TI - Lack of effect of cisapride on phenytoin free fraction. PMID- 1504388 TI - How much is the Pharm.D. worth to a student? PMID- 1504389 TI - Clinical pharmacology in two scientific medical journals. PMID- 1504390 TI - Comment: the new macrolide antibiotics and terfenadine. PMID- 1504391 TI - Parenteral and oral fluconazole for acute cryptococcal meningitis in AIDS: experience with thirteen patients. AB - OBJECTIVE: Cryptococcus neoformans infections of the central nervous system affect up to ten percent of AIDS patients. Standard therapy with amphotericin B with or without 5-flucytosine has a high rate of failure, relapse, and toxicity. Fluconazole is a new triazole antifungal agent available in both oral and intravenous forms that has shown efficacy in the primary and maintenance treatment of cryptococcal meningitis in AIDS patients. In this open, noncomparative trial, we evaluated the safety and efficacy of intravenous fluconazole followed by oral fluconazole in the treatment of acute cryptococcal meningitis in AIDS patients. METHODS: Thirteen AIDS patients with acute cryptococcal meningitis, or relapse after successful primary therapy, received 400 mg of intravenous fluconazole daily for 12-16 days followed by oral fluconazole 400 mg/d for the duration of primary therapy. If cerebrospinal fluid (CSF) cultures converted to negative within 32 weeks of treatment, the fluconazole dose was decreased to 200 mg/d as maintenance therapy. RESULTS: Fluconazole therapy was successful in six patients (46 percent) and unsuccessful in seven (54 percent). Of the seven patients considered unsuccessful, one demonstrated clinical improvement but remained CSF-culture positive, five were clinical failure and were switched to amphotericin B therapy, and one died after two weeks secondary to cryptococcal meningitis. No patient experienced any adverse reactions necessitating discontinuation of therapy. CONCLUSIONS: In this small group of patients, moderate doses of parenteral and oral fluconazole for acute cryptococcal meningitis in AIDS patients demonstrated failure rates similar to those reported in other studies with fluconazole and with amphotericin B. As there was no difference in initial Karnofsky scores or the severity of disease in treatment successes versus failures, it is difficult to determine who might respond to fluconazole as initial therapy or who should be treated initially with another agent. Further studies and clinical experience are needed. PMID- 1504392 TI - Possible correlation between glycemia and blood pressure in black, diabetic, hypertensive patients. AB - OBJECTIVE: To determine if there is any association between glycemia and blood pressure in black patients with hypertension and diabetes mellitus whose antihypertensive medications had been unchanged for six months. DESIGN: Retrospective, from March 1990 through February 1991. SETTING: Internal medicine ambulatory clinic at Detroit Receiving Hospital/University Health Center. PATIENTS: Patients seen during this period with hypertension and type II diabetes. Of the 639 possible subjects, 124 met the following criteria: (1) no change in antihypertensive medications for six months, (2) absence of secondary hypertension, and (3) weight change (if any) was less than five percent. Changes in antihypertensive medication(s) excluded 388 patients, secondary hypertension excluded 3, weight changes of more than five percent excluded 94, and lack of matching postprandial capillary blood glucose (PCBG) values excluded 30. The mean age of the subjects was 66.8 years, mean diabetes duration was 12.0 years, mean PCBG was 10.7 mmol, mean systolic blood pressure (SBP) was 1543 mm Hg, mean diastolic blood pressure (DBP) was 90.1 mm Hg. There were 28 men in the study and 96 women; 90 were obese (body mass index greater than 25 kg/m2) and 34 were nonobese. The diabetes was managed with insulin in 67 patients, with sulfonylureas in 50, and with diet in 7. INTERVENTION: None MAIN OUTCOME MEASURES: SBP and DBP versus PCBG at matching time both at baseline and at six months. RESULTS: There was a positive association between blood pressure measurements and glycemia. Overall change in SBP was strongly correlated with PCBG changes (r = 0.745, p less than 0.0001). Improved glycemia correlated with improved SBP control (r = 0.330, p less than 0.0024). Deterioration of glycemia correlated with a worsening of SBP control (r = 0.445, p less than 0.0053). The method of blood glucose control had no statistically significant effect (ANOVA) on these results. CONCLUSIONS: Glycemia is positively associated with blood pressure. PMID- 1504393 TI - Acceptance of a pharmacy-based, physician-edited hospital pharmacy and therapeutics committee newsletter. AB - OBJECTIVE: To assess the level of physician acceptance and perceived usefulness of a pharmacy-prepared, physician-edited pharmacy and therapeutics (P&T) committee newsletter. DESIGN: Two separate surveys conducted after 7 and 24 months of publication, respectively. SETTING: 500-bed, university-affiliated, tertiary-care hospital. MAIN OUTCOME MEASURES: The initial survey was mailed to physicians after 7 months of publication and they were requested to rate various aspects of the newsletter, including timeliness of articles, usefulness of articles, quality of writing and design, and overall value of the publication on a scale of 1-4: (1 = excellent, 2 = good, 3 = fair, 4 = poor). Physicians were also asked to rank different categories of articles (articles on new drugs, drug class reviews, topical reviews, formulary news, and articles providing P&T committee information) and were encouraged to provide comments. A separate follow up survey conducted at 24 months asked physicians to indicate whether they (1) regularly received the newsletter, (2) regularly read the newsletter, (3) found the information in the newsletter to be useful, and (4) desired to continue receiving the newsletter. RESULTS: Initial survey results yielded mean newsletter quality scores ranging from 1.54 to 1.66. Respondents preferred, in descending order, articles on new drugs, drug-class reviews, topical reviews, formulary news, and P&T committee information. The 24-month survey revealed that 96 percent of the physicians regularly receiving and reading the newsletter found the information useful and 97 percent felt that the newsletter should continue to be published. Favorable comments were also received from several prominent physicians. CONCLUSIONS: The results indicate strong physician acceptance of a pharmacy-prepared, physician-edited newsletter and provide information about the types of articles preferred by physicians in a university hospital setting. PMID- 1504394 TI - Development of a questionnaire for detecting potential adverse drug reactions. AB - OBJECTIVE: To develop a comprehensive list of symptoms categorized by body system as part of a questionnaire for detecting potential adverse drug reactions. DATA SOURCES: A preliminary list of symptoms in lay terminology was extracted from the "Side Effects" section of all drug monographs contained in the United States Pharmacopeia Dispensing Information (USP DI) computerized database (Volume II, Advice for the Patient) using natural language processing software. The list was sorted alphabetically and duplicate terms were eliminated. Symptoms were then categorized by body system or anatomic region. A preferred term for each symptom was selected when multiple synonyms and related words were listed. Finally, all of the symptom terms were incorporated into a thesaurus from which the questionnaire was derived. RESULTS: The questionnaire will be used as part of a computer-assisted interview, developed to solicit information from patients regarding their medication regimens and to systematically query them regarding the presence of salient symptoms or complaints. The computer system will eventually interface with the USP DI database to identify drugs from a patient's regimen that may be associated with adverse symptoms. The symptom thesaurus will provide the link to the USP DI database. Preliminary experience with the questionnaire in a limited number of patients has been encouraging. CONCLUSIONS: The questionnaire can assist clinicians in identifying drug-related symptoms including unreported adverse clinical effects of newly marketed or investigational therapeutic agents. When the questionnaire is computerized and linked to a comprehensive database, it can be more widely used to alert healthcare providers of potential adverse drug reactions that may otherwise go undetected. PMID- 1504395 TI - Relationships among prescription payment methods and interactions between community pharmacists and prescribers. AB - OBJECTIVE: This research was performed to examine community pharmacists' interactions with prescribers and to determine if these interactions are related to payment method. DESIGN: Randomly selected pharmacists (47 in chain pharmacies and 26 in independent pharmacies) collected data concerning prescriber interactions for a 40-hour period. These interactions were analyzed in terms of payment methods, prescriber acceptance, and types of information discussed. RESULTS: Information concerning 730 interactions by 72 pharmacists was obtained. Payment methods were related to the frequency of interactions per pharmacist (p less than 0.01). There were higher percentages of interactions for self-pay (median 2.2 percent) and Medicaid (median 1.8 percent) prescriptions than for third-party fee-for-service (mode 0 percent) or capitation prescriptions (mode 0 percent). Type of information discussed was related to payment method. The vast majority of information provided by pharmacists (91 percent) was accepted by prescribers. The rate of acceptance was 97 percent for prescriber-initiated interactions versus 88 percent for pharmacist- or patient-initiated interactions (p less than 0.01). CONCLUSIONS: Relationships between payment method and interactions were identified. These findings may be attributable to prescribing policies and reimbursement policies. Prescribing policies that restrict prescribers to a formulary may help make them become more adept at using those products; thus, they will make fewer prescribing errors. Reimbursement policies that require patients to consistently use a specific pharmacy (i.e., capitation) may help pharmacists become more familiar with the patient's prescription history. Therefore, interactions with prescribers are needed less frequently for these patients' prescriptions. PMID- 1504396 TI - Mercaptopurine-induced fever in a patient with Crohn's disease. AB - OBJECTIVE: To report a case of mercaptopurine-induced fever. CASE SUMMARY: A patient with Crohn's disease was treated with mercaptopurine (6-MP) for an exacerbation of his illness. The patient developed fever and chills. After thorough diagnostic examinations and failure to respond to antimicrobial therapy, symptoms were attributed to an allergic-type reaction to 6-MP. The patient defervesced after 6-MP withdrawal. Fever and chills, along with arthralgias, recurred upon rechallenge with a single dose of 6-MP. DISCUSSION: Adverse effects attributable to 6-MP therapy in inflammatory bowel disease were reviewed in the literature. Drug-induced fever has been previously reported; however, it is an uncommon adverse effect and is difficult to diagnose. It is also difficult to predict which patients will have the reaction. It is a diagnosis of exclusion requiring a thorough investigation. CONCLUSIONS: Drug-induced fever should be considered when confronted with fever and chills in patients with inflammatory bowel disease being treated with 6-MP. This case report shows the difficulty in differentiating between an infectious process and an adverse reaction to a medication. PMID- 1504397 TI - Cefaclor-associated serum sickness-like disease: eight cases and review of the literature. AB - OBJECTIVE: To describe the clinical features of serum sickness-like diseases (SSLD) in cefaclor-treated patients. DESIGN: Analysis of a case series spontaneously reported to Lyons Pharmacovigilance Center. SETTING: General and hospital practitioners and the French Network of Regional Pharmacovigilance Centers (FNRPC). PATIENTS: All reported cases with a possible causative relationship between cefaclor treatment and SSLD. MAIN RESULTS: Eight cases of SSLD following cefaclor treatment are described. The clinical features included cutaneous reactions, arthralgias, and moderate hyperthermia. In 50 percent of the patients, hospitalization was required because of incapacitating symptoms. The outcome was benign in all cases following discontinuation of the offending drug. All eight cases were reported in children under five years of age. Among 137 cefaclor-associated drug reactions collected by FNRPC, 27 cases of SSLD have been reported; 23 of these patients were younger than five years of age. A literature survey confirmed the higher reporting of SSLD in children with cefaclor compared with other antibiotics and suggested an incidence of 0.024-0.2 percent of SSLD per drug course of cefaclor. CONCLUSIONS: The case reports and epidemiologic studies confirmed the presumed role of age (patients under five years of age) in cefaclor-induced SSLD and the benign outcome despite severe clinical presentations in some reports. PMID- 1504398 TI - Nightmare cessation following alteration of ophthalmic administration of a cholinergic and a beta-blocking agent. AB - OBJECTIVE: To document the termination of nightmares brought about by an alteration in the ophthalmic administration of beta-blocking and cholinergic agents. PATIENT: A 75-year-old man residing in a long-term care facility experienced nightly nightmares of approximately one-year duration. INTERVENTION: Other potential causes for the nightmares were eliminated. The administration of the ophthalmic agents was evaluated and the resident was then instructed to alter administration to include closure of his eyes for one or two minutes after administration. OUTCOME: Following the alteration in administration the nightmares were not present and have not reappeared in the ensuing year. CONCLUSIONS: Ophthalmic application of beta-blocking and cholinergic agents is used for the treatment of glaucoma and has been reported to cause a wide variety of central nervous system effects. Researchers have documented reduced systemic absorption and enhanced ocular retention time with specific modifications in the administration of the ophthalmic products. Based on this research the suggestion has been made that systemic adverse effects may be reduced by altering administration through use of lid closure and lacrimal occlusion. This case validates this hypothesis and provides strong evidence for the need to counsel all patients receiving ophthalmic agents on proper administration, including techniques to reduce absorption in order to avoid undesirable systemic effects. PMID- 1504399 TI - Implication of dispensing cups in dosing errors and pediatric poisonings: a report from the American Association of Poison Control Centers. AB - OBJECTIVE: To characterize reports to poison centers involving liquid medication errors associated with the use of dispensing cups. DESIGN: Case series reported by 16 US poison centers over an eight-day period. SETTING: Calls to poison control centers, predominantly but not exclusively from homes. PATIENTS: Children and adults. RESULTS: Of 34 reported cases, most (79 percent) involved a two- to threefold dosing error, and most (94 percent) involved an error in a single dose of medication. Cough and cold preparations were implicated in 65 percent; acetaminophen elixirs in 18 percent. Three major causes of dosing errors were identified, including teaspoon/tablespoon confusion, assumption that the dispensing cup was the unit of measure, and assumption that the full dispensing cup was the actual dose. CONCLUSIONS: Dispensing cup markings should use a single unit of measure, and a uniform labeling system should be implemented. Teaspoon/tablespoon abbreviations should be avoided, and dispensing cup lettering should be more legible. Consumer education is essential to correct the misimpression that the full cup is always the recommended dose. PMID- 1504400 TI - Evaluation of medication knowledge in elderly patients. AB - OBJECTIVE: To identify problems with medication knowledge, self-estimated compliance, and recall of medication education in a group of elderly patients. DESIGN: Survey. SETTING: Medicine and geriatric clinics at a county hospital. PATIENTS: Patients greater than or equal to 60 years old and taking at least one prescription medication. MAIN OUTCOME MEASUREMENTS: Medication knowledge, self estimated compliance, and recall of medication education. RESULTS: The percent of geriatric patients correctly stating 76-100 percent of their medication doses, uses, and frequencies was 30, 64, and 66 percent, respectively. Fifteen patients (34 percent) stated they never missed a medication dose and 27 (61 percent) remembered to take their medications by memory alone. Sixteen and 86 percent, respectively, of the patients from the medicine and geriatric clinics could not recall receiving verbal or written educational material. Only 27 percent of patients recalled having been told about possible adverse reactions. The most frequently cited providers of medication information were physicians. CONCLUSIONS: Specially designed multidisciplinary medication education programs with repeated written and verbal reinforcement for elderly patients may improve patients' knowledge about their medications, recognition and management of adverse reactions, and compliance. PMID- 1504401 TI - Possible intraoperative anesthetic-sparing effect of parenteral ketorolac. AB - OBJECTIVE: Because the analgesic effects of ketorolac are equivalent to those of narcotic analgesics, we investigated the possibility that this non-steroidal antiinflammatory drug might also exhibit anesthetic-sparing properties similar to those described for narcotic agents. DESIGN: A nonrandomized, double-blind convenience sample. The treatment group received a preoperative dose of ketorolac 60 mg im 45 minutes prior to the induction of anesthesia. All other preoperative medications were identical. SETTING: Brooke Army Medical Center, a primary care setting. PARTICIPANTS: Six women requiring vaginal hysterectomies from American Society of Anesthesiologists class I/II, all of similar age, weight, and body surface area. OUTCOME MEASURES: End-tidal concentrations of the anesthetic gas were measured at five-minute intervals using a gas analyzer. A mean percent end tidal concentration versus time curve was generated for each group. RESULTS: The area under the concentration curves for the anesthetic gas in the ketorolac and control group were 15.9 +/- 5.1 and 52.3 +/- 13.4, respectively (p = 0.006). CONCLUSIONS: Ketorolac exhibits an anesthetic-sparing quality similar to that observed with narcotic analgesics. PMID- 1504402 TI - Hypersensitivity immune reaction as a mechanism for dilevalol-associated hepatitis. AB - OBJECTIVE: To assess lymphocyte reactivity to dilevalol and to serum containing putative ex vivo dilevalol antigens or metabolites in a case of dilevalol-induced liver injury. PATIENT: A 58-year-old woman with a clinical diagnosis of dilevalol induced liver injury. METHODS: Peripheral blood mononuclear cells collected from the patient were cultured in the presence of a solution of dilevalol and also with sera collected from a volunteer before and after dilevalol intake. A similar protocol was performed with lymphocytes from a healthy subject. RESULTS: No lymphocyte proliferation was observed either in the patient or in the healthy volunteer in the presence of dilevalol solutions. A significant proliferative response to serum collected after dilevalol intake was observed in the case of the patient compared with the proliferative response to the serum collected before the drug intake. No reactivity was found when lymphocytes from the healthy subject were tested under similar conditions. CONCLUSIONS: The methodology used allowed the detection of lymphocyte sensitization to sera containing ex vivo prepared dilevalol antigens, suggesting the involvement of an immunologic mechanism in dilevalol-induced liver injury. PMID- 1504403 TI - Weight gain associated with cinnarizine. AB - OBJECTIVE: To report four cases of cinnarizine-induced weight gain. DATA SOURCES: Case reports from a local obesity center and review articles. DATA EXTRACTION: Data were abstracted from spontaneous comments made by patients to one of the authors, who was a doctor at the clinic, and reviewed by the remaining authors. DATA SYNTHESIS: We reviewed the cases of four women, aged 50-57 years without endocrine or metabolic pathologies, that showed weight gain associated with the intake of cinnarizine for one to two years. No other drugs usually were administered during the period in which the women gained weight, although in two cases cinnarizine was associated with dihydroergocristine in the same medicine (Clinadil). The mean weight increase was 6.25 kg (range 4-10). The increases do not appear to be related to whether the patients' initial weight was ideal or excessive. The weight gain was always associated with increased appetite and food intake. One patient discontinued cinnarizine treatment and her weight returned to its previous level. CONCLUSIONS: Cinnarizine is a piperazine derivative used in the treatment of vertigo and in the prophylaxis of migraine. In contrast to related drugs, data about cinnarizine are scarce because randomized trials of cinnarizine have been inconclusive. Our observations indicate that cinnarizine may cause weight gain, as observed with other drugs in the same class. PMID- 1504404 TI - Ciprofloxacin-induced psychosis. AB - OBJECTIVE: To report a case of ciprofloxacin-induced psychosis and to discuss occurrence rates, risk factors, possible etiologies, preventive measures, and treatment courses for this adverse reaction. DATA SOURCES: Case reports and review articles identified by MEDLINE. DATA EXTRACTION: Data from pertinent published sources were reviewed and abstracted. DATA SYNTHESIS: A 49-year-old man developed symptoms of severe psychosis concomitant with ciprofloxacin (250 mg bid) treatment. Central nervous system effects secondary to ciprofloxacin treatment are uncommon and usually consist only of minor dizziness or mild headache, although rare occurrences of seizures and hallucinations have been reported. The mechanism by which ciprofloxacin causes these adverse effects is not fully understood. It has been suggested that quinolones may produce an epileptogenic effect by inhibiting the binding of gamma-aminobutyric acid to its receptor sites in the brain. There is yet no explanation for the occurrence of hallucinations or psychosis. CONCLUSIONS: Caution should be exercised when using ciprofloxacin in the treatment of patients with personality abnormalities or symptoms of psychosis. PMID- 1504405 TI - Corticosteroids in AIDS patients with Pneumocystis carinii pneumonia. PMID- 1504406 TI - Amantadine in the treatment of cocaine withdrawal. PMID- 1504407 TI - Aerosolized atropine as an antidote to nerve gas. PMID- 1504408 TI - Pentostatin: an adenosine deaminase inhibitor for the treatment of hairy cell leukemia. AB - OBJECTIVE: To review the pharmacology, pharmacokinetics, adverse effects, and various dosage regimens of pentostatin, and to evaluate the role of pentostatin in the treatment of hairy cell leukemia (HCL). DATA IDENTIFICATION: Articles were identified via an English-language literature search of MEDLINE (1966-91) and an extensive search of bibliographies from identified articles. STUDY SELECTION: Human clinical trials and case reports were selected for evaluation. DATA EXTRACTION: The literature was assessed for quality, methodology, and outcome information. DATA SYNTHESIS: At dosages of 4 mg/m2 administered every other week for 6-9 months, pentostatin has been shown to successfully induce a complete response in 58-90 percent of patients and to produce a partial response in up to 30 percent of patients with HCL. The median time to achieve a response is 4.7 months. Long-term remissions of at least 14 months' duration have occurred in some patients. Compared with interferon alfa alone, total response rates are not significantly different when pentostatin and interferon alfa are used in combination. When dosed appropriately, pentostatin is generally well tolerated. Common adverse effects include nausea, vomiting, myelosuppression, fever, and infection. CONCLUSIONS: Pentostatin is a purine analog that inhibits adenosine deaminase, a key enzyme necessary for purine salvage. Pentostatin has received labeling approval for the treatment of HCL refractory to a minimum of three to six months of treatment with interferon alfa. Based on current data, pentostatin will be a useful addition to the therapeutic agents presently available to patients with HCL. Ongoing trials are evaluating the effectiveness of pentostatin as first-line therapy for patients with HCL. PMID- 1504409 TI - Psychotropic drug-related rhabdomyolysis. AB - OBJECTIVE: The objective of this review is to discuss the pathophysiology and potential etiologies of rhabdomyolysis in psychiatric patients, with an emphasis on psychotropic drug-induced rhabdomyolysis. DATA SOURCES: References were obtained through an on-line search of MEDLINE, using English-language and human literature only. STUDY SELECTION: Because the topic is a potential drug-induced adverse effect, no controlled studies are available. Most of the literature are case reports and series of case reports. DATA EXTRACTION: The quality of case reports was assessed using the Food and Drug Administration guidelines for assessing the causality of a potential adverse drug reaction. DATA SYNTHESIS: The results of this review are based on qualitative data and indicate that rhabdomyolysis in psychiatric patients can be from multiple etiologies, including agitation, dehydration, and intramuscular injections, as well as an adverse effect of psychotropic medications. Although the deficiencies of this type of data are recognized, it is the only type of data often available to assess the etiology and causality of an uncommon adverse event. CONCLUSIONS: Rhabdomyolysis in psychiatric patients can be caused by many factors, both drug- and non-drug related. Rhabdomyolysis is more likely to occur when patients are faced with a combination of risk factors. When combinations of factors are present (e.g., aggression and restraints, intramuscular injections, and extrapyramidal effects), or when muscle trauma from an individual factor is sufficiently traumatic, muscle necrosis may occur to the point that rhabdomyolysis ensues. PMID- 1504410 TI - Selective decontamination of the digestive tract in intensive care patients: review and commentary. AB - OBJECTIVE: To evaluate the benefits, risks, and costs of antimicrobial regimens used for selective decontamination of the digestive tract (SDD) in intensive care unit (ICU) patients. DATA SOURCES: Information was obtained from clinical trials, review articles, abstracts, and textbooks. Key indexing terms included antibiotics, selective decontamination, and infections. STUDY SELECTION: Research articles describing controlled clinical trials of SDD in medical or surgical ICU patients were reviewed. Trials that investigated transplant, cirrhotic, leukemic, or oncology patient populations were excluded. DATA EXTRACTION: The details of studies that evaluated nosocomial infection or nosocomial pneumonia rates were extracted. These included study design, demographics, SDD regimens, severity of illness scores, and colonization, infection, and mortality rates. DATA SYNTHESIS: The use of SDD in mechanically ventilated surgical or trauma ICU patients reduces the incidence of colonization, nosocomial pneumonia, and overall infection rates, but does not change the overall mortality rate. Administration of antibiotic and antifungal agents in a nasogastric suspension is required for SDD. The addition of systemic prophylactic antibiotics or oropharyngeal paste was not required to decrease nosocomial infections. The most frequently studied SDD regimen (colistin/amphotericin B/tobramycin) is not feasible for use in the US because of exorbitant drug costs. Less expensive alternatives include norfloxacin/nystatin, or colistin/nystatin/gentamicin. CONCLUSIONS: Additional research is required before SDD regimens can be routinely recommended in surgical and trauma ICU patients. A multicenter study is warranted to determine the long-range benefits, potential for resistance, and cost-effectiveness of SDD. PMID- 1504411 TI - Metoclopramide: an analysis of inappropriate long-term use in the elderly. AB - OBJECTIVE: To present a case of possible metoclopramide-induced tardive dyskinesia and document the frequent use of metoclopramide for inappropriate lengths of treatment in elderly, ambulatory subjects. DESIGN: Descriptive study that identified long-term users of metoclopramide among a population of 4515 elderly subjects. SETTING: Participants in an ambulatory health-screening program in Florida (Florida Geriatric Research Program). PARTICIPANTS: Individuals (2898 women and 1617 men) over the age of 65 years who volunteered for annual health screening. INTERVENTIONS: All medication histories for participants were reviewed to identify subjects who reported metoclopramide use on at least one visit to the program. RESULTS: Thirty-four participants (0.75 percent) reported the use of metoclopramide during at least one visit. Eleven subjects (32.4 percent) reported that they had used this drug for longer than one year. Nine of the 34 subjects (26.5 percent) also reported the use of metoclopramide at their next annual visit. CONCLUSIONS: Results from this study suggest that metoclopramide is frequently prescribed inappropriately to treat gastrointestinal disorders. Long term use of this drug exposes patients to an unnecessary risk of adverse drug reactions. PMID- 1504412 TI - Short- and long-term retention of a nursing home education program on metered dose inhaler technique. AB - OBJECTIVE: To evaluate an education program on metered-dose inhaler (MDI) technique designed for nurses and trained medication aides (TMAs). DESIGN: The education program included a handout, a lecture incorporating a videotape on correct inhaler and device technique, and hands-on experience with placebo inhalers. The participants' ability to verbalize and demonstrate correct MDI technique was assessed by the same two-person teams before, immediately after, and two months after the program. SETTING: Five nursing homes. PARTICIPANTS: Fifty-six nurses and TMAs practicing in nursing homes. MAIN OUTCOME MEASURES: Learning and retention. RESULTS: The participants' mean (+/- SD) verbal and demonstration scores increased immediately after the program by 68 +/- 18 points for verbalization and 47 +/- 16 points for demonstration. The participants were always better at demonstrating than verbalizing MDI technique. The participants' baseline verbal and demonstration scores correlated with the amount learned. Learning was influenced by the individual nursing home (verbal and demonstration) and personal use (demonstration only), but not by academic degree, previous training, past instruction of a patient, or current care of a patient who was receiving inhaler therapy. After two months, the scores were lower than immediately after the program test by 0-92 points for verbalization and 10-80 points for demonstration; however, the mean scores were still significantly greater (p less than 0.05) than the baseline scores. Retention of knowledge on the correct technique was greater for the demonstration component. Retention was influenced only by the nursing home in which the participant worked, and not any of the other variables. CONCLUSIONS: Our structured education program significantly improved inhaler technique; however, to maintain retention of the material, the program should be frequently repeated. PMID- 1504413 TI - Hepatic and renal dysfunction following nafcillin administration. AB - OBJECTIVE: To review four cases of combined hepatic and renal toxicity that may be associated with the administration of nafcillin in adults. This type of adverse event with the use of nafcillin has not been previously documented in the literature. DATA SOURCES: References from pertinent articles are identified throughout the text. DATA SYNTHESIS: Nafcillin is a widely used penicillinase resistant penicillin. In four patients receiving nafcillin doses greater than 9 g/24 hours, changes in renal and hepatic function markers were noted within 72 hours of the initiation of nafcillin therapy. Laboratory values returned toward baseline when nafcillin therapy was discontinued. Elevations in blood urea nitrogen, creatinine, total bilirubin, and lactate dehydrogenase have been previously described in the literature for penicillin-like agents other than nafcillin. The exact mechanism for such toxicities as well as patient risk factors have not been clearly established. CONCLUSIONS: Caution should be taken when initiating nafcillin therapy. Evaluation of renal and liver function tests prior to initiating nafcillin therapy and within the first 72 hours appears warranted. If hepatic and/or renal toxicity is observed, discontinuation of nafcillin should be considered. PMID- 1504414 TI - A description of a pharmacotherapy curriculum in a university-based family medicine program. AB - OBJECTIVE: To describe the methods by which a family medicine residency program implements a pharmacotherapy curriculum. The goal of the curriculum is to teach family medicine residents the principles of rational drug therapy. SETTING: A university-based family medicine residency program. TEACHING STRATEGIES: Specific learning objectives are discussed and the following teaching strategies are expanded upon: (1) monthly noon conferences; (2) a printed formulary and pharmacotherapy handbook; (3) a pharmacy and therapeutics committee; (4) policy statements for drug representatives and use of samples; (5) an on-site pharmacy; (6) quarterly newsletter; and (7) inpatient consultation coverage. PHARMACIST ROLE: The role and responsibilities of the pharmacy faculty and pharmacist(s) who implement this curriculum and the methods used to evaluate its effectiveness are also described. The availability and funding of the pharmacy faculty member can sometimes be arranged with local schools of pharmacy seeking clerkship sites. Interaction with pharmacy students also serves to enhance the educational experience of the family medicine residents. CONCLUSIONS: The family medicine program implements a comprehensive curriculum designed to teach family medicine residents the principles of rational drug therapy. The curriculum may be expanded upon as necessary, or, if the entire program is not feasible, certain elements may be extracted and applied in other institutions. PMID- 1504415 TI - Pharmacy's version of "The Wizard Of Oz". PMID- 1504416 TI - All-Pharm.D. Degree alone will not significantly alter the pharmacy profession. PMID- 1504417 TI - Analysis of IgA antibody to Pseudomonas aeruginosa in sera and sputa of patients with chronic airway diseases. AB - The change of IgA system for Pseudomonas infection was examined by enzyme-linked immunosorbent assay of the system in sera and sputa of patients with chronic airway diseases. The anti-Pseudomonas total IgA antibody titers in both sera and sputa were not elevated in group I with no infection (mainly chronic bronchitis) and group II infected with bacteria other than Pseudomonas, but were elevated in group III colonized transiently with Pseudomonas [diffuse panbronchiolitis (DPB) and bronchiectasis] and group IV colonized persistently with Pseudomonas (mainly DPB). The elevation in the sera and sputa were mainly due to monomeric IgA and polymeric IgA (S-IgA), respectively, and values were significantly higher in group III than in group IV only in the sera. These results indicate that the IgA system is enhanced in advanced DPB and bronchiectasis complicated by Pseudomonas infection, and that the anti-Pseudomonas IgA antibody titer in serum is more useful than that in sputum for the diagnosis of respiratory Pseudomonas infection. PMID- 1504418 TI - Localization of exercise-induced myocardial ischemia with ST depression. AB - This study was undertaken to determine whether the site of ST depression on 12 lead exercise electrocardiography can identify the ischemic site assessed by myocardial Tl-201 emission computed tomography in 409 patients with transient defects. ST depression in some leads was more frequent in those with inferior or lateral ischemia than in those with anterior ischemia. In 214 patients with ST depression and no ST elevation, however, the frequency of ST depression in each lead was similar between those with and without anterior ischemia. In 63 patients with ST depression, single vessel disease and no infarction, the frequency of ST depression in each lead was similar among those with anterior, inferior and lateral ischemia. Moreover, in patients with abnormal Q waves, the site of ST depression was not related to the location of ischemia. In conclusion, the site of exercise-induced ST depression could not be used to determine an ischemic region. PMID- 1504419 TI - Ultrasonography in the diagnosis of aldosterone-producing adenoma: is it useful? AB - The usefulness of ultrasonography (US) in the diagnosis of aldosterone-producing adenoma(s) (APA) was compared with computed tomography (CT) and adrenal scintigraphy in 13 patients. The initial examination with US could demonstrate four of seven right APA. Repeat examinations later in two patients whose tumors were initially not detectable did reveal a tumor in one patient. On the other hand, two left APA were delineated on the initial trial. The other seven left APA, except two small APA in one patient, could be delineated during repeat US examinations performed on other days. With CT, all APA were detected during the first or second trial except for the smallest one. The rate of localization by adrenal scintigraphy with dexamethasone pretreatment was 11 of 13 patients. CT had the highest localization rate. However, US was shown to be useful in the localization diagnosis of APA on repeat examinations with a high delineation rate comparable to CT. PMID- 1504420 TI - Diagnosis and management of endobronchial tuberculosis. AB - We examined the records of sixty-one patients (17 males and 44 females) with endobronchial tuberculosis (EBTB). Smear tests of acid-fast bacilli were positive in 42 cases and cultures of tubercle bacilli (TB) were positive in 57. The main findings of chest roentgenogram on admission were as follows: no abnormal findings in 8, atelectasis in 30, infiltration in 25, and cavitary lesions in 6. The localization and cross-sectional extension of lesions confirmed bronchoscopically were as follows: trachea in 15, with 3 circular lesions (CLs). Right (R-) main bronchus in 19 with 11 CLs, left (L-) main bronchus in 18 with 11 of CLs, R-truncus intermedius in 14 with 6 of CLs, R-upper lobar bronchus (UB) in 17 with 12 CLs, R-middle lobar bronchus in 14 with 11 of CLs, R-lower lobar bronchus (LB) in 6 with 2 CLs, L-UB in 10 with 7 CLs and L-LB in 3 with 2 CLs. All cases were treated by combination chemotherapy with isoniazid, rifampicin, streptomycin and/or ethambutol and the rate of negative conversion of TB was good, but most of circular lesions resulted in severe bronchial stenosis or complete obstruction during and after chemotherapy, and no improvement was seen in any of the atelectasis cases at the cessation of chemotherapy. We discuss the points of early diagnosis and management of EBTB. PMID- 1504421 TI - Cell profile and elastase activity in diffuse panbronchiolitis investigated by bronchoalveolar and bronchial lavage. AB - To examine the mechanism of tissue damage which causes bronchiolectasis in diffuse panbronchiolitis (DPB), the cellular components, elastase and its main inhibitor, alpha 1-protease inhibitor (alpha 1-PI) were measured in bronchoalveolar and bronchial lavage fluid (BALF and BLF) from 14 DPB patients. A predominant increase in the neutrophil count was observed in DPB. Elastase activity in BALF and BLF was about 1,000-fold higher in the DPB group than in the control group. An inhibitor study and a positive correlation between elastase activity and the neutrophil count in both lavage fluids from the DPB group indicated that the activity was mainly that of neutrophil elastase. Western blot analysis of alpha 1-PI showed that most of the alpha 1-PI in the lavage fluids from DPB group was degraded. These results indicated that neutrophil infiltration increases the level of elastase in the DPB lesions; this increase seems to be closely related to tissue damage. PMID- 1504422 TI - The first report of a case with acute myocardial infarction showing familial deficiency of creatine kinase. AB - A 46-year-old male patient was diagnosed as suffering from acute myocardial infarction, but his serum creatine kinase (CK) level was extremely low and no CK isozymes were detected in the serum. The total CK activities in the skeletal muscle amounted to only 2% of that of the control. Electrophoresis of the CK isozymes in the skeletal muscle showed that CK-MM was absent but the CK-BB and abnormal isozyme bands were present. There was no evidence of myocardial ischemia, although the exercise treadmill test revealed ST segment depression in the chest leads. One of the patient's sisters had an extremely low serum CK level suggesting inheritance of this abnormality. This is the first report of a case showing familial deficiency of CK. PMID- 1504423 TI - Bence-Jones myeloma with pleural effusion: response to alpha-interferon and combined chemotherapy. AB - A 73-year-old female patient with myelomatous pleural effusions is described. She was admitted to our hospital with lumbago and emaciation. Laboratory findings revealed cytopenia and hypogammaglobulinemia. Immunoelectrophoresis demonstrated Bence-Jones monoclonal protein in the serum, but not in the urine. Bence-Jones myeloma was diagnosed by the bone marrow aspiration. Chest X-ray film, however, showed bilateral pleural effusions. Fluid cytology revealed numerous immature plasma cells, indicating pleural involvement. Intrapleural administration of alpha-interferon combined with systemic chemotherapy (oral melphalan-prednisolone with alpha-interferon im.) was successful in maintaining the resolution of pleural effusions. Intrapleural alpha-interferon administration seems to be effective in the management of myelomatous pleural effusions. PMID- 1504424 TI - Horseshoe kidney and membranous glomerulonephritis with cold activation of complement. AB - A 48-year-old woman was admitted to our hospital because of proteinuria associated with persistent hypocomplementemia. Intravenous pyelography indicated the presence of horseshoe kidney without other abnormalities. Hypocomplementemia was caused by cold activation of complement. There were some findings suggestive of chronic liver disease (positive HCV antibody, hypergammaglobulinemia, low cholinesterase, etc.). Percutaneous renal biopsy showed the features of multiple evolutional phases of membranous glomerulonephritis. PMID- 1504425 TI - Meningioma developed 25 years after radiation therapy for Cushing's disease. AB - A 44-year-old woman who had been therapeutically irradiated with 45 Gy to the sellar lesion for Cushing's disease has been in remission for 25 years. A large but asymptomatic brain tumor was accidentally found in the right middle fossa by a routine follow-up computed tomography. Upon surgical removal of the tumor, the histology revealed a fibroblastic meningioma. Although the incidence of meningioma following irradiation to pituitary adenoma is rare, a follow-up computed tomography should be taken to any possible late onset, and curable complication. PMID- 1504426 TI - Hereditary angioedema: a case with ascites yet no symptoms in the family. AB - An interesting case of hereditary angioedema in a 26-year-old female is reported, with a finding of transient effusion of fluid into the peritoneal cavity during the attacks. The patient suffered from recurrent abdominal pain for several years, but no family members had any similar symptoms. In spite of repeated hospital admissions and many examinations, accurate diagnosis was not made until the most recent admission. The recognition of hereditary angioedema as a cause of acute and/or recurrent abdominal pain may avoid useless invasive procedures and lead to adequate treatment in other similar cases. PMID- 1504427 TI - Methyldopa-induced colitis in a patient with membranoproliferative glomerulonephritis. AB - A 76-year-old man with membranoproliferative glomerulonephritis complicated by methyldopa-induced colitis is reported. Eight months after administration of methyldopa, mucous bloody stool was noted. A barium enema examination showed disappearance of haustra and a spastic rectosigmoid with pseudo-polyposis. Biopsy specimens obtained from the sigmoid mucosa revealed interstitial edema and small inflammatory cells. After cessation of methyldopa treatment, the sigmoid findings, blood pressure, and proteinuria were improved, suggesting that methyldopa not only induced the acute colitis but also worsened the nephrotic syndrome in this patient. PMID- 1504428 TI - Interstitial nephritis associated with glomerulonephritis in a patient with Hashimoto's disease and idiopathic portal hypertension. AB - A middle-aged women with hypothyroidism, idiopathic portal hypertension and nephrotic syndrome is presented. This unusual clinical appearance could not be explained as SLE by serological examinations. Pathohistological examinations showed "Banti's liver", Hashimoto's thyroiditis and diffuse proliferative glomerulonephritis with severe tubulo-interstitial nephritis. Immunohistochemical studies revealed IgA deposits in glomeruli. Electron microscopic study disclosed peculiar lucent areas of rarefaction with osmiophilic particles in tubular basement membranes. This tubulointerstitial nephritis was considered to be related to the immunological mechanism involving thyroid gland, liver and kidney disorders. This case thus had a clinically rare combination of these three. PMID- 1504429 TI - A successful therapy with plasma exchange for interstitial pneumonia of progressive systemic sclerosis. AB - A 47-year-old woman who was diagnosed as progressive systemic sclerosis (PSS) had acute and severe interstitial pneumonia. Based on the results of her chest roentgenogram, computed tomography, transbronchial lung biopsy (TBLB) and bronchoalveolar lavage (BAL), her interstitial pneumonia was considered to be atypical of PSS. Although she was treated with corticosteroid, methylprednisolone pulse therapy and immunosuppressive drug, the effect of these drugs was insufficient as treatment for the interstitial pneumonia. Therefore, plasma exchange was attempted. After plasma exchange was carried out for three days, her symptoms improved as well as the laboratory data and chest roentgenogram without any severe side effects. We recommend plasma exchange for interstitial pneumonia of PSS as an effective treatment. PMID- 1504430 TI - Primary malignant lymphoma of the trachea and subglottic region. AB - A 44-year-old female was admitted with the complaint of choking. On fiberbronchoscopic examination, multiple, polypoid lesions with a smooth surface were exhibited at the cervical trachea. Histological diagnosis was B-cell malignant lymphoma, diffuse, medium sized cell type (LSG classification). No other lesions were detected in the systemic evaluation. After combined chemotherapy and regional irradiation, the tumor disappeared. The clinical and pathological characteristics of this case are similar to those of malignant lymphoma of mucosa-associated lymphoid tissue (MALT). PMID- 1504431 TI - Hemoglobin Andrew-Minneapolis (beta 144 (HCl) lysine----asparagine) in a Japanese family. AB - Hemoglobin Andrew-Minneapolis, an abnormal hemoglobin with an asparagine residue substituted for a lysine at position 144 of the beta-globulin chains, was identified in three members of two generations in a Japanese family. The carriers of hemoglobin Andrew-Minneapolis showed false high levels of hemoglobin A1c, as measured by the standard cation exchange high performance liquid chromatography, and a moderate tendency for erythrocytosis. This family is the first report of this abnormal hemoglobin in Japan. PMID- 1504432 TI - Hypokalemic paralysis associated with distal renal tubular acidosis. AB - A 68-year-old man had hydronephrosis due to ureteral stones for two months earlier and then increasing muscle weakness developed. A 30-year-old woman had rapidly progressive quadriparesis. In both cases, severe hypokalemia with metabolic acidosis was observed and the diagnosis of distal renal tubular acidosis was made. The former was considered to be an idiopathic incomplete form and the latter was a secondary complete form associated with Sjogren syndrome. Hypokalemic paralysis may occur as a complication of distal renal tubular acidosis. PMID- 1504433 TI - An autopsy case of intravascular lymphomatosis (neoplastic angioendotheliomatosis) accompanied by high fever, hypertension and without focal sign. AB - A 75-year-old woman suffered from intermittent high-grade fever and hypertension without any focal sign. Serum lactic dehydrogenase (LDH) was markedly elevated. The fever was resistant to antibiotics and temporarily sensitive to prednisolone. She had heart failure and died. Postmortem examination revealed intravascular proliferation of B lymphocytes, indicative of the diagnosis of intravascular lymphomatosis. The clinical diagnosis is usually very difficult because of the absence of pathognomonic clinical manifestations. PMID- 1504434 TI - Ehlers-Danlos syndrome combined with von Recklinghausen neurofibromatosis. AB - We recently had the opportunity to study a 25-year-old male with both Ehlers Danlos syndrome (EDS) and von Recklinghausen neurofibromatosis (VRNF). We describe the clinical manifestations of the case and discuss the probable pathomechanism of the combination of the two syndromes, with a review of the literature. As recent literature suggests that both syndromes are linked to chromosome 17, we conclude that their combination is not coincidental, but genetically linked. PMID- 1504435 TI - Follicular bronchiolitis associated with rheumatoid arthritis. AB - Follicular bronchiolitis is a rare disorder, though it has been recognized as a pulmonary involvement of rheumatoid arthritis in recent years. A 57-year-old woman with rheumatoid arthritis was admitted to the hospital with persistent productive cough and breathlessness on exertion. An open lung biopsy was performed to establish a definite pathologic diagnosis of her disease, and she was diagnosed as having follicular bronchiolitis on the basis of the histopathological findings. It is essential to differentiate this disease from other bronchiolar or lymphoproliferative disorders of the lung. PMID- 1504436 TI - Lupus nephritis associated with bacterial panperitonitis and lung alveolar hemorrhage. AB - A 36-year-old woman was admitted to the hospital with the diagnosis of nephrotic syndrome due to lupus nephritis. The patient had panperitonitis caused by Staphylococcus aureus as a complication, and an emergency laparotomy was performed. After the operation, the patient developed a massive lung alveolar hemorrhage. Methylprednisolone pulse therapy showed a marked effect on the lung hemorrhage. It is known that lung alveolar hemorrhages associated with systemic lupus erythematosus have a very high mortality; the present case is relatively rare because of the good response to steroid pulse therapy. PMID- 1504437 TI - Sweet's syndrome associated with subacute necrotizing lymphadenitis. AB - A 34-year-old man with Sweet's syndrome associated with subacute necrotizing lymphadenitis is reported. Histological examination of an erythematous, painful, cutaneous plaque revealed a dermal interstitial neutrophilic infiltrate. A biopsy specimen obtained from an inguinal lymph node showed granulomatous formation, consisting of histiocytes, with central necrosis in the paracortex and macrophages in the sinus. Although the causes of the two diseases remain obscure, this appears to be the first report of Sweet's syndrome associated with subacute necrotizing lymphadenitis. PMID- 1504438 TI - The first report of diffuse panbronchiolitis in Korea: five case reports. AB - Diffuse panbronchiolitis (DPB), which is prevalent in Japan, is known to be rare outside Japan. Although a case of diffuse panbronchiolitis in a second generation Korean was reported in Japan in 1986, no case has been reported in Korea. Recently we found 5 cases of diffuse panbronchiolitis in Korea, two histologically proven and three clinically and radiologically suspected. All 5 cases had the typical respiratory symptoms and signs and a history of chronic sinusitis. In three clinically and radiologically suspected cases, high resolution computed tomography showed the typical findings of DPB and other diseases such as pulmonary emphysema, bronchial asthma, chronic bronchitis and bronchiectasis could be ruled out. More cases of DPB are expected to be found in Korea in the near future. PMID- 1504439 TI - A new variant of alpha-1-antitrypsin deficiency (Siiyama) associated with pulmonary emphysema. AB - A 38-year-old male with pulmonary emphysema due to severely reduced serum alpha-1 antitrypsin (AAT) level (14.5 mg/dl) was found to have an inherited new AAT deficient variant Siiyama. Chest roentgenogram and CT scanning revealed advanced emphysema, and severe obstructive ventilatory impairment was observed. During the 4-year follow-up period, the annual rate of decline of FEV 1.0 showed approximately 10-fold greater than the normal decline in FEV 1.0 (-380 ml/yr). Treatment with tamoxifen in order to raise the serum AAT level only resulted in an insufficient increase. Augmentation therapy of human AAT should be considered in the future. PMID- 1504440 TI - Acute renal failure following hypokalemic rhabdomyolysis due to chronic glycyrrhizic acid administration. AB - A 72-year-old man developed acute renal failure (ARF) following severe hypokalemic rhabdomyolysis. The hypokalemia was due to chronic glycyrrhizin (glycyrrhizic acid) administration. Although glycyrrhizin-induced hypokalemic rhabdomyolysis has been occasionally reported, the association of this type of rhabdomyolysis with ARF has not been described. In the present case, there was a sensitivity to glycyrrhizin the preceding renal insufficiency, and dehydration which was thought to have contributed to ARF. It should be recognized that elderly patients with such predisposing factors may be susceptible to a rapid deterioration of renal function after glycyrrhizin-induced hypokalemic rhabdomyolysis. PMID- 1504441 TI - Over-the-counter self-medication. The issues. PMID- 1504442 TI - Nimodipine. A review of its pharmacological properties, and therapeutic efficacy in cerebral disorders. AB - Nimodipine is a dihydropyridine calcium antagonist which dilates cerebral blood vessels and increases cerebral blood flow in animals and humans. Preliminary findings reveal its potential benefit for the treatment of a wide range of cerebrovascular disorders, particularly for prophylaxis and treatment of delayed ischaemic neurological deficits resulting from cerebral vasospasm in patients with subarachnoid haemorrhage. Studies involving patients aged up to 79 years have confirmed these preliminary findings by showing that nimodipine reduces the incidence of severe ischaemic deficit after subarachnoid haemorrhage. Initial results from studies of patients with acute ischaemic stroke indicate that nimodipine, started within 72 hours of onset, improved recovery, particularly in patients over 65 years. However, other investigators have found no marked difference in 6-month mortality or morbidity rates of stroke patients aged up to 97 years. Findings from other studies suggest that nimodipine may improve symptoms of cognitive dysfunction in elderly patients. Nimodipine is well tolerated by both younger and older patients. The most frequently reported adverse event has been hypotension. Thus, nimodipine therapy offers important benefits as part of the approach to management of patients with subarachnoid haemorrhage and has potential in other cerebral disorders, including stroke and impaired cognitive function, although confirmation of initial results in patients with cerebral impairment are required. PMID- 1504444 TI - The management of diabetic proteinuria. Which antihypertensive agent? AB - Diabetic renal disease is a clinical syndrome in which proteinuria is followed by the development of renal failure, and is commonly associated with the concomitant development of hypertension. In insulin-dependent diabetic (IDDM) patients, hypertension often first appears in the microalbuminuric phase of diabetic nephropathy whereas in non-insulin-dependent diabetic (NIDDM) patients, hypertension often antecedes nephropathy and may precede the diagnosis of diabetes. Antihypertensive regimens including diuretics, vasodilators such as hydralazine, beta-blockers and ACE inhibitors reduce proteinuria and delay the decline in renal function in IDDM patients with established nephropathy. No such data are as yet available for calcium antagonists. In microalbuminuric diabetic patients with hypertension, conventional antihypertensive agents, ACE inhibitors and calcium antagonists have been shown to decrease urinary albumin excretion. In the diabetic patient with normal blood pressure and microalbuminuria, there is much less information. It appears likely that ACE inhibitors reduce or retard the rate of increase in albuminuria in these patients. The effect on ultimately delaying or preventing renal failure remains unknown although the preliminary evidence is encouraging. Data on calcium antagonists remain inconclusive with some reports suggesting an increase in proteinuria with the dihydropyridine calcium antagonists. However, a recent longer term study suggested that nifedipine may prevent the rise in albuminuria which is generally observed in the untreated normotensive microalbuminuric subject. PMID- 1504443 TI - Pharmacological treatment strategies in age-related cataracts. AB - Cataract is the major cause of blindness worldwide and at present the only approved treatment in many countries including the UK and USA is surgical removal of the lens. In other countries various anti-cataract drugs are available without proof of their efficacy. Research is continuing into the possible benefits of several groups of drugs and some vitamins. The first to be studied were sorbitol lowering agents (aldose reductase inhibitors) based on the sorbitol hypothesis for diabetic cataract. Sorbitol-lowering agents have distinct effects in vitro and many of them delay the development of cataract in galactose-fed rats. A few delay cataract in diabetic rats but none have been proved effective in clinical trials, although these continue. Aspirin, paracetamol (acetaminophen) and ibuprofen delay diabetic cataract in rats, and have been shown to delay other experimental cataracts. Case-control studies from 3 continents indicate that these drugs, or at least aspirin, protect against cataract. Results of studies on all 3 drugs indicate a benefit even at low doses. Population-based studies did not identify any protection against early lens opacities but tiny opacities that do not impair vision are not a problem. Bendazac protects lens proteins in vitro and delays cataractogenesis in x-irradiated rats. In humans, it reached the clinical trial stage but most trials have been small and with subjective criteria of opacification. One objectively monitored trial suffered from a high drop-out rate. Other preparations studied less extensively include vitamins, aminoguanidine to prevent protein cross-linking in diabetes and agents designed to boost glutathione levels. It is probable that some agents which may delay or prevent cataract will be proved effective soon, and in the end there may be different drugs to delay cataract in different high risk groups. This is what might be expected of a multifactorial disease, although compounds that intervene in the final common pathways to cataract could have a broad efficacy. PMID- 1504445 TI - The use of oral fluoroquinolones in nursing home patients. AB - The approach to management of patients with presumed infection in the nursing home is influenced by the limited availability of diagnostic tests and support staff. Although antibiotics are most often prescribed in the absence of laboratory data, many studies indicate that empirical therapy for nursing home infections is relatively successful. With the scrutiny on containment of healthcare costs, therapy of nursing home patients has been changing and will continue to shift toward treatment within nursing homes without transfer to a hospital. Better oral antimicrobial agents with a wide spectrum of activity, such as the fluoroquinolones, will play a major role in the treatment of many infections acquired in the nursing home. Because of the favourable characteristics of the fluoroquinolone agents, they should be useful for elderly patients who develop infections in nursing homes. They have excellent in vitro activity against Gram-negative bacteria which are often multidrug-resistant and are common in nursing home patients. Studies indicate that absorption of orally administered fluoroquinolones is very efficient in the elderly and these drugs are well tolerated. Numerous clinical trials have documented good efficacy of the fluoroquinolones in the treatment of elderly patients for the most common infections in the nursing home, including urinary tract infections, respiratory tract infections and skin infections. PMID- 1504447 TI - The pathophysiological role and therapeutic implications of platelet activating factor in diseases of aging. AB - Platelet activating factor (PAF) is a unique phosphoglyceride which possesses many potent biological activities relevant for the pathogenesis of diseases of the elderly. PAF is generated and released by numerous cell types and tissues and is rapidly metabolised through a well defined metabolic cycle. Its biological actions are mediated via direct and indirect stimulatory effects on target cells and tissues. The current knowledge of PAF and its role in cardiovascular disease, thromboembolism, cerebral ischaemia and neurodegenerative disorders are discussed in detail. It is likely, that in future, a better understanding of the pathophysiological and physiological roles of PAF will provide new strategies for the treatment of human diseases of aging. PMID- 1504446 TI - Impotence in elderly men. AB - Impotence is a highly prevalent condition occurring in 10 million American men over the age of 18 years. Alterations in vascular supply, hormonal changes with age, neurological dysfunction and the use of a variety of medications may combine and contribute to impotence. Impotence should not be considered a normal part of the aging process. Careful attention to evaluation for the aetiology of impotence will lead to making appropriate therapeutic choices. PMID- 1504448 TI - Adverse reactions as a cause of hospital admission in the aged. AB - Truly elderly people comprise an increasingly large fraction of the population and consume a disproportionate amount of drugs. Over the last 25 years a number of different studies have illustrated that advancing age is associated with adverse drug reactions (ADRs). Advancing age is also associated with polypharmacy and multiple pathology, and this complex inter-relationship makes it difficult to conclude that age itself is a causative factor for ADRs. ADRs resulting in hospital admission have been the subject of study for many years, but it has not been consistently demonstrated that advancing age is a predisposing factor. Early studies used the method of intensive inpatient monitoring and identified digoxin, diuretics, aspirin, psychotropics and cytotoxics as drugs of concern. Smaller more recent studies have used more sophisticated statistical techniques to identify predisposing factors. Nonsteroidal anti-inflammatory drugs have been added to the list of drugs that may cause ADR-related hospital admission. Polypharmacy, and altered pharmacokinetics and pharmacodynamics are possible causative factors; however, variable compliance and multiple pathology may cause difficulties with attributing causality. Some basic guidelines for sensible prescribing would almost certainly result in fewer ADRs in the elderly, including those ADRs severe enough to result in hospital admission. PMID- 1504449 TI - Rapid induction of atherosclerosis in rabbits. AB - Japanese white rabbits fed a restricted amount (100 g/head/day) of an atherogenic diet (AD) containing 0.2% cholesterol and 6% peanut oil showed mild and persistent hypercholesterolemia (338 +/- 79 mg/dl). They developed atherosclerotic lesions 4 weeks after deendothelialization of aorta carried out at the 4th week of AD-feeding. This rabbit model of atherosclerosis has such advantages as being able to be produced in a short period and having similar biochemical and pathological characteristics with those in human atherosclerosis. PMID- 1504450 TI - Bronchial-associated lymphoid tissue (BALT) response to airway challenge with cigarette smoke, bovine antigen and anti-pulmonary serum. AB - The bronchial-associated lymphoid tissue (BALT) is a lymphoepithelial organ, related to the immune defence of the lung and to alveolar clearance, which changes size in certain states of disease. Changes in the size of BALT were quantified and compared, and Spearman's test was used to test the relation with the bronchial epithelium. A total of 180 rats were used, divided into 6 groups of 30 as follows: 1) untreated controls; 2) exposed to cigarette smoke for two months; 3) treated with anti-pulmonary serum three doses daily over five days; 4) exposed to cigarette smoke and treated with anti-pulmonary serum; 5) sensitized with bovine albumin and exposed to an environment containing this antigen for two months; 6) exposed to cigarette smoke and bovine albumin. The lungs were processed for histological study, and were stained with the PAS-Alcian blue method. The main left bronchi BALT was studied, and the following were quantified: Lymphatic area (LA), as a percentage of the lung surface occupied by BALT; the flat epithelium (FEp), as the length of bronchial epithelium anatomically related to LA, whose cells tend to adopt a flat shape; the Contact epithelium (Cep), as the length of bronchial epithelium which is in direct contact with the LA. A percentage count of bronchial cells was made in the following classifications: globet cells; globet cells stained with the PAS-Alcian blue method; flat cells; lymphoepithelium cells; columnar cells; and bronchial epithelium cells excluding the above two cell types.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1504451 TI - Presence of melanin in normal human Schwann cells. AB - The presence of melanin granules in Schwann cells of unmyelinated nerve fibres in the normal skin of a black woman is demonstrated by electron microscopy. Pathological conditions associated with the differentiation ability of Schwann cells for melanogenic are reviewed. This capacity may be due to the common origin of Schwann cells and melanocytes in the neural crest. PMID- 1504452 TI - Studies on the interaction between titin and myosin. AB - This study examines the interaction of titin and myosin. In order to analyze the domains of myosin contributing to the binding for titin, we conducted a solid phase binding assay. Different portions of myosin (heavy chains, light chains and myosin fragments) were coated on the microtiter wells and reacted with biotinylated titin. Then the binding of biotinylated titin to these polypeptides was detected by using the avidinbiotin-peroxidase method. The results demonstrated that light meromyosin and subfragment 1 were the major domains of myosin interacting with titin. Titin fragments obtained by trypsin digestion were allowed to react with myosin in an affinity column, and the bound fragments were isolated by an acidic elution. Immunoblot analysis of myosin-bound titin fragments revealed that an A-band domain of titin was responsible for the binding of myosin. In addition, biotinylated titin labelled the outer A-bands and Z-bands in intact myofibrils, thus confirming the in situ binding of titin to myosin. PMID- 1504453 TI - A scanning and transmission electron microscopic study of the membranes of chicken egg. AB - Questions regarding the structure of the inner and outer shell membranes of the chicken egg were addressed in this study by correlating observations from light microscopy and scanning and transmission electron microscopy. The egg membrane had a limiting membrane, which measured .9 to .15 microns in thickness and appeared to be a continuous and an impervious layer, but the shell membrane did not. Under the SEM, each membrane was seen to be made up of several fibre layers. In the tear preparations viewed under the SEM two layers were observed in the egg membranes and three to five layers in the shell membrane, with an apparent plane of cleavage between each layer. Each fibre was made up of a central core and an outer mantle layers. The central core was perforated by channels which measured .08 to 1.11 microns in diameter and ran longitudinally along the length of the fibre. Between the mantle layer and the fibre core was a gap or cleft measuring between .03 to .07 microns. The diameter of the fibres of the inner layer of the egg membrane ranged between .08 to .64 microns, whereas those of the outer layer of the same membrane ranged from .05 to 1.11 microns. Fibres in the shell membrane ranged from .11 to 4.14 microns diameter. PMID- 1504454 TI - In vitro analysis of the cellular resistance to chemotherapeutic BCNU. AB - Our assays in vitro show that BCNU inhibits cell proliferation in the C6 cell line experimental glioma and is dose-dependent, starting from 0.5 microgram/ml of the drug with just an hour of exposure. For every tested concentration of BCNU it is shown that, from the fifth day after exposure, cellular resistance appeared. This resistance is justified by the capacity of cell DNA reparation. A study of the clonogenic capacity of the C6 cells exposed to BCNU also shows the appearance of cellular resistance for doses of 0.5 microgram/ml and 1 microgram/ml. Furthermore, the exposure of C6 cell cultures to BCNU at these levels produces a cellular evolution towards more differentiated morphological patterns. PMID- 1504455 TI - Hematoencephalic barrier. Ultrastructure and histophysiology of the endothelium capillary of the neuronal nuclei of the mesencephalon. AB - The ultrastructure of the dorsal periaqueductal nucleus capillaries of the mesencephalon in the cat was studied under the electron microscope in relation to the hematoencephalic barrier, and its four structural levels: 1. Endothelium; 2. Basal membrane; 3, Pericytes; and 4. Glial prolongations. An analysis was performed of what occurs in these four components (in a non-experimental histophysiological state, and without manipulation by markers) in the thinnest capillaries of the centre of the mesencephalic neuronal nucleus. Special attention was placed on the first diffusion barrier formed by the endothelium capillary as the intimate guardian of the Central Nervous System (C.N.S.) neurons. The C.N.S. capillaries are formed from the continuous endothelium, with no fenestrations, and hermetic joining complexes, without pinocytosis vesicles on both sides of the plasmatic membrane (adluminal and external), and surrounded by a continuous basal membrane. The non-fenestrated capillaries of the C.N.S. are less permeable than those with similar characteristics located in other areas. In the C.N.S. these capillaries form a selective physiological barrier which determines the size of the molecules that are permitted to cross the capillary wall. It is suggested that the electron-dense globules found in the endothelium cytoplasm may be molecules assimilated from the blood, which might represent the first level or step to the selective diffusion entrusted to the hematoencephalic barrier. It is also suggested that the elongated electron-dense particles found in the endothelium cytoplasm and basal membrane may be macromolecules which are normally retained for an active defensive function. They would represent the first and second level or steps of the retention performed by the hematoencephalic barrier which blocks their passage to the confined space of the perivascular capillary. PMID- 1504456 TI - Ultrastructure of murine cardiac ganglia in experimental Chagas' disease. AB - Albino mice, infected with Trypanosoma cruzi (Tulahuen strain) were sacrificed on days 7, 9, 12, 14, 16, 18, 21, 32 and 39 following infection. Transmission electron microscopic examination of the cardiac ganglia revealed no ultrastructural change at day 7. At day 9 there was peri- and intraganglionic monocytic infiltration but parasites were absent. Between days 12 and 16 there was intense monocytic infiltration, with intra-ganglionic presence of parasites within fibroblasts, monocytes and macrophages. None were seen within capsular cells, endothelial cells, Schwann cells, satellite cells and ganglion cells. The Schwann cells and satellite cells, however, showed phagocytic activity. Satellite cells were also reactive with proliferative pseudopodia which encircled neuronal processes. By day 18, parasites were absent in the ganglia. But monocytes were still present up to day 39, some of them still engulfing satellite cell and neuronal processes. Satellite cells continued to be reactive and Schwann cells phagocytic. Ganglion cells remained normal throughout the experiment. The results suggest that infection of Schwann cells, satellite cells and ganglion cells may depend upon the tissue tropism of the strain of the parasite used and its concentration in the inoculum. The results are consistent with the view that any parasympathetic dysfunction in experimental Chaga's disease in the mouse may be of a transient nature. PMID- 1504457 TI - Structural and ultrastructural modifications of adenohypophyseal gonadotropic cells in goat (Capra hircus) in anoestrus, gestation and milk production. AB - The structural and ultrastructural modifications of the gonadotropic cells of goats were studied with an immunohistochemical method (peroxidase antiperoxidase), in anoestrus, gestation and milk production. The cell type which predominates in anoestrus corresponds in its morphological characteristics to the classic FSH cells, and has two populations of homogeneous and electrodense secretory granules (141-244 nm and 244-400 nm in diameter), rough endoplasmic reticulum of flat cisternae and many large-sized lysosomes. During gestation secretory granules show a characteristic reduction in size and are less abundant; lysosomes are also more scarce and the endoplasmic reticulum shows a high development; dilated and intercommunicated cisternae show a slight electrodense content, characteristic of typical LH cells. During milk production the cells show an increase in the number of secretory granules which are still small, and an increase in the number of lysosomes which appear as in anoestrus. PMID- 1504458 TI - Distribution of neuropeptide Y-like immunoreactivity in the brain of Salmo salar and Gambusia affinis. AB - Through the immunohistochemical PAP technique, the distribution of immune positive neurons and fibres for an antibody anti-NPY in the encephalon of salmon fixed in Bouin have been located and studied. NPY-positive neurons are found forming three important nuclei: in the ventrolateral telencephalon; in the tegmentum mesencephali; and in the locus coeruleus. Neurons in the optic tectum, in the thalamic region and a few in the preoptic recess have also been located. The fibres were found throughout the brain, with the exception of the cerebellum, presenting a greater density in three regions: in the dorsal telencephalon; in the mesencephalon; and in the visceral lobes in the rhombencephalon. With the aim of proving if this distribution is found in other groups of teleosts, we processed, with the same technique, the advanced teleost Gambusia affinis, in order to compare it with the primitive teleost Salmo salar. The results show that in both fish this neuropeptide has the same pattern of distribution. The results also suggest that in fish this neuropeptide can be involved in several functions of the central nervous system, as has been demonstrated for mammals. The innervation of the visceral lobes and also the presence of NPY-fibres in the posterior hypothalamus are anatomical supports of the studies which suggest that NPY is related to the control of the food intake. PMID- 1504459 TI - Scanning electron microscopic and light microscopic observations on morphological changes of freeze-dried bone implantation in rats: comparison with fresh autogenous bone transplantation. AB - Bone remodelling after the implantation of freeze-dried autogenous bone in rat parietal bone was compared with fresh autogenous bone transplantation, using a scanning electron and light microscope revealed the time intervals after transplantation/implantation. The light microscope revealed the time delay of the bone remodelling in the implantation, compared with the transplantations. The scanning electron microscope showed that the differences between the two groups were in the states of bone union and bone resorption. In the fresh bone group, the newly-formed bone filled the spaces between host and the transplanted bones at 2 to 3 weeks after the transplantation: the newly-formed bone fused and melted into the transplanted bone. New bone formation was more dominant on the bone surface in the dura mater side than in the skin side. The union was almost completed at 5 weeks. In freeze-dried bone implantation, the bone union in the contact space was very poor and the implanted bone was mainly covered by the new bone, which developed from the host bone surface in the dura mater side at 2 to 3 weeks after the implantation. What is noteworthy is that bone resorbed areas showing numerous Howship's lacunae were mainly observed on the host bone surface in the vicinity of newly-formed bone. However in freeze-dried bone implantation, the bone resorption was greater on the host and implanted bone surface than that of fresh bone transplantation: the resorption of host bone was considerably larger at certain periods after freeze-dried bone implantation. The present results show that the healing process of freeze-dried bone implantation, even though autogenous bone was used, differed from that of fresh autogenous bone transplantation, and the differences are concerned not only with time sequences but also with qualitative changes. This suggests that the host would have some different responses to the freeze-dried autogenous bone from fresh materials. PMID- 1504460 TI - Monoclonal antibody against histiocytosis X cells. AB - Monoclonal antibody against histiocytosis X cells (HXCs) was established. The antigen was the cell membrane of HXCs from the submandibular lesion of a 63-year old man who had been diagnosed as an adult type of histiocytosis X (HX) and whose HXCs had numerous Birbeck granules (BGs). The obtained monoclonal antibody, named MI1, reacted with the antigenic cell membrane of HXC. Immunoblotting showed that MI1 bound to the cell membrane of 28500 mw. MI1 also reacted with interdigitating reticulum cells (IDCs) in the tonsil and Langerhans cells (LCs) in the epidermis. MI1 reacted with the BGs which connected to the cell membrane, but not with those located near the nucleus. PMID- 1504461 TI - Morphometric studies on the development of human thyroid gland in early fetal life. AB - Histological and morphometric studies were performed on 30 thyroid glands obtained from normal human fetuses. Their crown-rump length (CRL) ranged from 57 to 190 mm, corresponding to the gestational age of 10-20 weeks. The weight of the thyroid gland increased proportionally in relation to CRL, foot length and fetus weight. The first follicles containing PAS-positive colloid were observed in the peripheral part of the thyroid gland of 57 mm CRL fetus. The number of follicles per 1 mm2 of thyroid surface section increased up to 85 mm CRL and thereafter gradually declined for the end of studied period of fetal life. The volumes (in mm3) of thyroid epithelium, colloid and stroma, beginning from 85 mm increased proportionally to the CRL while the height of epithelial cells did not change. The epithelium/colloid ratio decreased notably to 165 mm CRL and thereafter remained constant. Results of the present study suggest that the thyroid gland of human fetus approaches structural maturity in 17.5 week of gestation. PMID- 1504462 TI - Kupffer cells and PIMs in acute experimental African swine fever. AB - An ultrastructural study of Kupffer cells and pulmonary intravascular macrophages (PIMs) of healthy and African Swine Fever (ASF)-infected pigs was carried out. A vascular perfusion method was performed in order to obtain an optimal intravascular morphology and tissue fixation. The infection developed acute ASF lesions in both organs. Both Kupffer cells and PIMs were studied at different stages of infection. The differences observed in both macrophagic cells from uninfected and infected tissues are shown and discussed. PMID- 1504463 TI - Age-related morphometric changes occurring in the somata of astrocytes of the granular layer of rat neocerebellar cortex (Crus I and Crus II). AB - A quantitative study concerning the age-related changes occurring in the cell body and somatic organelles of neocerebellar astrocytes is carried out, using rats aged 2 to 24 months. Manual stereological techniques are used to determine the following parameters on electron micrographs: the somatic volume, the volume density and the absolute volume of the protoplasmic structures as well as the mean surface of the rough endoplasmic reticulum cisternae per cell. None of the parameters reveals any clear-cut general temporal pattern. The soma and the cell components show statistically significant differences in the parameters with ageing, excepting the dense bodies (relative and absolute volumes) and the Golgi apparatus (relative volume). There are significant positive linear trends between, on the one hand, the somatic volume and, on the other hand, the absolute volume of either of the following structures: nucleus, glial filaments, ground substance and dense bodies. Some linear correlations between the absolute volumes of organelles are also found. Despite the ability for karyokinesis, it is concluded that astrocytes do undergo changes with ageing. PMID- 1504464 TI - The toxic effects of bis (tributyltin) oxide on the rat thoracic aorta. AB - The toxic effects of bis (tributyltin) oxide (TBTO) on the ultrastructure and permeability of rat thoracic aorta were studied electron microscopically and the accumulation sites of tin were determined with an X-ray microanalyzer. Male Wistar rats received 0.05ml/kg of TBTO as an emulsion in 1 ml of distilled water through a stomach tube. After time intervals of 2, 4, 6, 8, 10, 12 h after intubation, thoracic aortae were isolated and prepared for electron microscopy. Marked swelling of mitochondria in the aortic endothelial cells appeared at 4 h after TBTO treatment. By x-ray microanalysis, tin L-alpha peaks (3.44 keV) were obtained from these swollen mitochondria. Subendothelial edema progressed between 6 and 8 h after TBTO treatment. By tracer experiment, it was seen that large amounts of peroxidase reaction products filled the expanded subendothelial space. At 12 h after TBTO treatment, degenerative changes of the endothelial cells were prominent. These results indicated that orally administered TBTO accumulated in the mitochondria of the endothelial cells of thoracic aorta. The direct toxic effects of TBTO on mitochondria might induce severe damage to the endothelial cells and cause disturbance of the permeability barrier function of the endothelial layer and subendothelial edema. PMID- 1504465 TI - Histopathology of the pituitary gland in neonatal little (lit) mutant mice. AB - The pituitary gland in the little (lit) mutant mouse was analyzed with respect to the cytoarchitecture of the pars distalis and the volumetric density of immunoreactive growth hormone (GH) cell granules in neonatal lit/lit and normal C57BL mice. At 8 days postnatally the volume of GH granules/total tissue was significantly less in the lit/lit pars distalis, and the cells were loosely arranged, as compared with the normal pars distalis. In newborn mice a statistically significant difference could not be detected between normal and lit/lit mice with respect to the volumetric density of GH granules; however, differences occurred in the cytoarchitectural organization of the pars distalis. These differences included prominent vascular channels and well-defined cords and clusters of cells in the normal newborn mice, in contrast to indistinct vascular elements and a more diffuse arrangement of cells in lit/lit. PMID- 1504466 TI - Transforming growth factor-alpha expression in rat experimental hepatocarcinogenesis. AB - Growth factors in general and transforming growth factor-alpha in particular have been related to cell proliferation and cell differentiation. This study was designed to clarify the distribution pattern of TGF-alpha in chemically-induced hepatocarcinogenesis. Sprague-Dawley rats were subjected to different non intensive or intensive carcinogenic treatments using diethylnitrosamine (DEN) as carcinogen and ethinyl estradiol (EE) as promoter. The livers were fixed in 2% paraformaldehyde, dehydrated in a series of ethanol solutions, embedded in paraffin and sectioned. In the preneoplastic lesions no TGF-alpha immunoreactive cells were identified, but in some hepatic tumours cell immunostained with TGF alpha antibody were observed. These results suggest that the cells capable of expressing TGF-alpha constitutively may be involved in neoplastic development in vivo. PMID- 1504467 TI - Retinal photoreceptor fine structure in the red-backed salamander (Plethodon cinereus). AB - The retinal photoreceptors of the red-backed salamander (Plethodon cinerus) have been studied by light and electron microscopy. Rods and single cones are present in this duplex retina in a ratio of about 25:1. The photoreceptors in this amphibian species are much larger than is reported for most vertebrates. In the light-adapted state, rods reach deep into the retinal epithelial (RPE) layer. The rod outer segment is composed of discs of uniform diameter displaying several very deep incisors. The rod inner segment displays a distal elliposid of mitochondria and a short stout myoid region. Rod nuclei are electron dense and often protrude through the external limiting membrane. Rod synaptic spherules are large and display several invaginated synaptic sites as well as superficial synapses. It is felt that the rods do not undergo retinomotor movements. The cone photoreceptors are much smaller than the rods and display a tapering outer segment, an unusual modified ellipsoid and a large parabolid of glycogen in the inner segment. Cone nuclei are less electron dense than rods and are located at all levels within the outer nuclear layer. The synaptic pedicle of the cones is larger, more electron lucent and display more synaptic sites (both invaginated and superficial) than that of rods. It is felt that cone photomechanical responses are minimal. PMID- 1504468 TI - Retinal pigment epithelial fine structure in the red-backed salamander (Plethodon cinereus). AB - The retinal pigment epithelium (RPE) of the red-backed salamander (Plethodon cinerus) consists of a single layer of large squamous shaped cells. The RPE cells are but minimally infolded basally (sclerally) but show many large apical (vitreal) processes interdigitating with the rod outer segments. These epithelial cells are joined laterally by prominent tight junctions located in the mid region of the cells. Internally smooth endoplasmic reticulum is very plentiful while rough endoplasmic reticulum is not. Polysomes, small dense mitochondria and small round to oval melanosomes are plentiful. Golgi zones and lysosome-like bodies are also present as are phagosomes of outer segment material and myeloid bodies. The RPE cell nucleus is large and vesicular. It is felt that the melanosomes undergo retinomotor movements but as only light-adapted specimens were examined it is not known how extensive are these movements. Bruch's membrane or complexus basalis shows the typical pentalaminate structure noted for most vertebrates. The choriocapillaris is a single layer of large anastomosing capillaries which are minimally fenestrated facing Bruch's membrane. PMID- 1504469 TI - Carbohydrate cytochemistry of bonnet monkey (Macaca radiaca) nasal epithelium. Response to ambient levels of ozone. AB - The main purpose of this study was to determine whether exposures to ambient levels of ozone induced changes in the carbohydrate content in the anterior nasal cavity of bonnet monkey. Monkeys were exposed to 0.00. 0.15, or 0.30 ppm of ozone for 6 or 90 days, 8 hours/day. Monkeys treated for 90 days to 0.15 or 0.30 ppm of ozone displayed damaged ciliated cells and a new cell type in their respiratory nasal epithelium, the "intermediate" cells possessing morphological characteristics of both ciliated and secretory cells. Characterization of the secretory cell carbohydrates with the PA-TCH-SP, HID-TCH-SP and LID-TCH-SP techniques indicated the existence of periodate-reactive sulfated and carboxylated polysaccharides in both treated and control monkeys. Ozone inhalation, however, induced the appearance of a large number of mucous cells with dilated cisternae of rough endoplasmic reticulum compared to controls, which reacted negatively for sugar presence. In addition, in the respiratory epithelium ozone induced the increase of cells with intracytoplasmic lumina containing material reacted positively for sulfated and carboxylated polysaccharides. PMID- 1504470 TI - Morphometric study on the interhemispheric asymmetries in the Wistar rat and the effects of early experience. AB - Sixty male Wistar rats were used for this experiment and assigned at random to the control group or to the stimulation method. Control rats show cerebral asymmetry with right bias at the frontal and occipital lobes. In the case of stimulated rats the differences from the occipital zone increase while those from the frontal lobe disappear. PMID- 1504471 TI - Expression of HBsAg and HBcAg in liver tissue: correlation with disease activity. AB - The patterns of Hepatitis B surface antigen (HBsAg) and Hepatitis B core antigen (HBcAg) expression were studied in liver biopsies taken from 41 patients with chronic HBV disease. Immunohistochemical methods were used on deparaffinized sections for the identification of HBsAg and HBcAg in liver tissue. Twenty-one of the 41 cases (51.2%) were classified as inactive liver disease and 20 (48.8%) as active liver disease. In liver biopsies with inactive disease, HBsAg demonstrated varying types of cytoplasmic expression in a rather high number of hepatocytes distributed mainly in clusters, while HBcAg was rarely expressed in liver nuclei. On the other hand, in liver biopsies with active disease HBsAg was characterized by a diffuse cytoplasmic expression in a few discrete hepatocytes, while HBcAg was expressed in the nuclei of the hepatocytes in 70% of the cases and in half of the positive cases it was also detected in the cytoplasm. In conclusion, HBsAg expression in a few scattered hepatocytes correlates with active liver disease and positive HBcAg, while varying HBsAg cytoplasmic expression in a rather high number of clustered hepatocytes is related to chronic inactive liver disease and negative expression of HBcAg. PMID- 1504472 TI - The phylogenetic odyssey of the erythrocyte. III. Fish, the lower vertebrate experience. AB - The piscine erythrocyte can be considered the prototype of the red cells that are distributed among inframmalian vertebrates. It is a permanently nucleated, hemoglobin-ladened, oval, flattened, biconvex disc. Ultrastructurally it demonstrates a cytoskeleton comprised of a marginal band and a membrane skeleton which are responsible for the erythrocyte's conversion to an ellipsoid during morphogenesis and endow it with resilience to physical trauma. Erythropoiesis initiates in the yolk sac, followed in many fishes, by the intermediate cell mass. These sites are the sources of the transitory, primitive generation red cells which apparently make their first phylogenetic appearance in fishes and which are subsequently represented in all classes of vertebrates including mammals. Production of definitive generation erythrocytes is centered in evolutionary "pre-splenic" tissue of the gastrointestinal tract or in the spleen in cyclostomes, dipnoi, and chondrichthyes while in teleosts it is typically located in the kidneys with or without splenic participation. The blood is a major site of erythrocyte maturation in the lower fishes and exhibits significant numbers of immature erythroid cells plus occasional mitotic figures. Some teleosts also circulate developing erythroid cells. Certain fishes have occasional circulating erythroplastids, conceptually a portent of phylogenetic changes in higher vertebrates. Remarkably, some bristlemouths have denucleated erythrocytes exclusively in the circulation. The largest piscine erythrocytes are found in the dipnoi, myxines, and chondrichthyes. Primitive fish with the exception of the endothermic sharks tend to have lower hemoglobin concentrations than the modern teleosteans. The very highest hemoglobin concentrations are attained by the endothermic scombrids. Erythrocyte-based data have a broad extent and are variably affected by age, sex, season and environment. This report includes a substantial selection of illustrations (fish species and rbc micrographs). PMID- 1504473 TI - Submucosal plexus of terminal ileum: a study of the cholinergic and noradrenergic nerves in rats with streptozotocin-induced diabetes. PMID- 1504474 TI - Epidemiology of essential hypertension and diabetes mellitus. AB - Essential hypertension and diabetes mellitus are highly prevalent and potentially lethal chronic diseases in the US population. Both have ocular complications that can result in permanent vision loss. Ten risk factors for hypertension and six risk factors for diabetes are discussed to help practicing doctors of optometry screen, refer, educate, monitor and co-manage patients who have one or both of these diseases. PMID- 1504475 TI - In-office laboratory testing for diabetes mellitus. AB - New technology has made accurate blood glucose determination a possibility within all optometric practices. This paper reviews the technology, methodology, and potential sources of error in office glucose testing. PMID- 1504477 TI - Hypertension and diabetes: a clinicolegal review. AB - The optometric management of patients with essential hypertension and diabetes mellitus is determined by both clinical and legal requirements. The most common cause of litigation is failure to recognize retinal changes requiring treatment, combined with a failure to refer. To comply with appropriate standards of care, an optometrist should perform a thorough eye examination (including evaluation of the retina with a dilated fundus examination), educate patients concerning the risks of hypertension or diabetic retinopathy and the need for periodic assessment, describe pertinent findings to the patient's treating physician, schedule patients for periodic reevaluation (as required by examination findings), and refer patients promptly if sight-threatening retinal changes are encountered. PMID- 1504476 TI - Co-management of patients with hypertension or diabetes. PMID- 1504478 TI - Diagnosis, pathogenesis, and management of essential hypertension. AB - Hypertension, defined as systemic blood pressure equal to or exceeding 140/90 mm Hg, is a common health problem afflicting approximately 20% of the adult population of the United States. Ninety-five percent have "essential hypertension" for which the pathogenesis is unknown, although both genetic and environmental factors probably are important. Using proper technique, multiple blood pressure determinations made both inside and outside the physician's office are used to diagnose hypertension and assess the effects of treatment. The goal of therapy is to reduce the morbidity and mortality attributable to high blood pressure, which is accomplished by reducing blood pressure to below 140/90 mm Hg. Treatment involves both nonpharmacologic and pharmacologic modalities. Because noncompliance remains a major problem, proper selection of therapy is important. Cooperation of all health care professionals who deal with hypertensive patients is important to ensure control of this common health problem. PMID- 1504479 TI - Ocular manifestations of hypertension. AB - Systemic hypertension is a highly prevalent clinical condition encountered in optometric practice on a daily basis. Hypertension produces, both directly and indirectly, a variety of ocular manifestations for which the patient may seek optometric care, or which may be detected by the optometrist during the course of examination. Determination of the patient's blood pressure status through thorough history taking and patient examination, including in-office sphygmomanometry screening, offers a tremendous opportunity for holistic optometric care that has a positive impact on patient longevity and quality of life. This review of hypertensive fundus changes provides an in-depth historical perspective of the ocular manifestations of systemic hypertension, the current clinical and basic research thinking on the pathophysiology of observed hypertensive ocular changes and its appropriate documentation, and the clinical application of this important information in the primary care optometric setting. PMID- 1504480 TI - Diagnosis, pathogenesis, and management of diabetes mellitus. AB - Proper care of the patient with diabetes mellitus poses a challenge for all health care professionals. The diagnosis is often established at the onset of symptoms. Early diagnosis through screening of patients at high risk allows prompt initiation of therapy and may help prevent long-term complications. The fasting plasma glucose determination is the most useful diagnostic test, but random plasma glucose and the oral glucose tolerance test are also used to diagnose diabetes, depending on the circumstances. Complex insulin programs and frequent self-monitoring of blood glucose are required to achieve acceptable glucose control in patients with insulin-dependent diabetes mellitus. Treatment of non-insulin-dependent diabetes mellitus requires a choice among diet, sulfonylureas, insulin, or a combination of these therapies. Achievement of treatment goals requires diet, monitoring, education, and continuing care in addition to medication. A general understanding of these goals may help the optometrist participate more effectively in the care of this challenging and important class of patients. PMID- 1504481 TI - Ocular manifestations of diabetes mellitus. AB - Diabetes mellitus afflicts approximately 14 to 15 million Americans and is a leading cause of new blindness in the United States. Since eye disease represents an end-organ response to a generalized medical condition, all structures of the eye are susceptible. Furthermore, diabetes produces multiple effects on visual function and visual acuity that require specific clinical consideration. This paper offers a review of some of the key ocular manifestations of diabetes mellitus. PMID- 1504482 TI - [The concept of continuing education in medical service--competence of physicians in counseling in the field of (social) medicine, law and economics]. AB - The paper describes the performance of continuing education programmes of the Medical Advisory Services in Germany and explains the methodical background. Elements of conceptional structure comprise basic and advanced seminars, professional und special training courses. Realizations of this training concept are described with special regard to demand, utilisation and acceptance with prospects of future. PMID- 1504483 TI - [Behavior and attitude regarding skin cancer prevention and early detection in relation to current knowledge--studies of visitors to an industrial fair]. AB - During the course of the 42nd International Trade Fair 1990 in Munich a total of 1245 visitors were interrogated with regard to their education in the early recognition of skin cancer, and their behaviour in respect of exposure to sunlight. The same persons were also subjected to melanoma screening, both with regard to special assessment of pigment lesions and inspection of the entire skin. The questionnaire showed that women were better informed than men. Approximately 87% of the questioned women had heard of the problems of melanoma, whereas only about 55% of the men belonged to the informed group. The knowledge of cancer education proved to be above average in the age group between 30 and 60 years. Persons with ample knowledge on melanoma education demonstrated more motivation to take part in cancer prevention examinations and also in examinations relating to other organ systems. Thus, the necessity of cancer screening examinations was substantially more often a matter of course among women than among men. The occurrence of skin cancer on the own body as well as its occurrence in members of one's own family does not guarantee essential knowledge on melanoma education, although in the informed group the percentage of persons directly or indirectly affected by melanoma, was higher. With regard to the behaviour towards sunlight, young people dealt more cautiously and consciously with the sun than those aged 45 and over who had exposed themselves to sunlight without exercising any caution, especially in the past.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1504484 TI - [The Charlottenburg Allergy Prevention Program 90. Early detection and prevention of allergic diseases by modifying mass screening of 3d grade students]. AB - On the one hand, the Charlottenburg allergy prevention programme showed the spread of allergic diseases among the pupils of the third form of public schools, and on the other hand it familiarized parents, teachers and pupils with health promotion schemes under the slogan These who are informed well in time will suffer less. For the first time within the area of Berlin, the Charlottenburg district developed a quality standard in respect of screening and health promotion connected with allergy. This new focal point of attention was set up by means of mass screenings of pupils while at the same time critically reviewing previous routine methods, weeding out unnecessary procedures and emphasizing the essential. The difficult tasks confronting Public Health services in this regard could not be managed without outside help. This was forthcoming from partners recruited from the university, the sickness insurance bodies and self-help groups. The cooperation that developed in this manner was exemplary and might serve as a model for future on-target health prevention programmes. PMID- 1504485 TI - [Epidemiologic studies of the occurrence of Salmonella heidelberg in the Leipzig area]. AB - This paper reports on observations regarding the appearance of Salmonella heidelberg (S. heidelberg) in the Leipzig district. Included are all isolations of S. heidelberg from 1985 to 1989 in human and veterinary materials as well as surface water and sewage. Our results show that this serovar--originating in a poultry farm--is spreading quickly among the animal stock of the northern part of the former Leipzig district. Parallel to that, S. heidelberg infections in the population increase strongly, with territorial differences. Besides partially very severe clinical findings, the incidence of human germ excretors is very high. Temporal and local parallels to the spreading of the serovar in animal and man are also seen in the surface water and sewage samples. The epidemiological observations and the possible routes and modes of transmission of S. heidelberg are discussed. PMID- 1504486 TI - [The aims of German medical anthropology in countries of the European Community]. AB - Medical Anthropology deals with the anthropological conditions of health, illness and health care in different societies and cultures, and has to be distinguished in that respect from Social and Industrial Medicine in German language countries which could be considered a kind of official and governmental medicine. While in North America Medical Anthropology has been established at nearly all universities and medical colleges during the last 25 years, corresponding activities in Germany and most other European countries have not reached university level up to now. After referring to general anthropology during the period of enlightenment and to philosophical and medical anthropology in the first half of our century, both to be considered forerunners of medical anthropology in german-speaking countries, an outline of medical anthropology in German-speaking countries, an outline of medical anthropology in the USA is given followed by a survey of questions and problems with which medical anthropology in German-speaking and other European countries has to cope, and would be confronted after the opening of the EC Market in 1993. The article concludes by briefly going into the circumstance of teaching medical anthropology in the Federal Republic of Germany. PMID- 1504487 TI - [An accident at work or an occupational accident? The verdict of the Federal Social Court of Saarland 23 January 1992--regulation L2U53/91, S3U18/90]. PMID- 1504488 TI - [Physical therapy in mucoviscidosis]. PMID- 1504489 TI - [Diabetes mellitus in childhood and adolescence]. PMID- 1504490 TI - Ear wax: a new biological monitoring medium for metals? PMID- 1504491 TI - Blood lead level as a criterion of global pollution. PMID- 1504492 TI - Total mercury and methylmercury in hair, maternal and umbilical blood, and placenta from women in the Seville area. PMID- 1504493 TI - Inflammatory response and resistance in lead-treated mice. PMID- 1504494 TI - Effect of mercury on tissue glutathione following intrarenal injection of mercuric chloride. PMID- 1504495 TI - Cadmium concentrations in plants and goats tissues from various areas of Chalkidiki, Greece. PMID- 1504496 TI - Genetic markers in relation to different exposures. PMID- 1504497 TI - Dermal exposure of pesticide applicators in staked tomato (Lycopersicon esculentum Mill) crops: efficiency of a safety measure in the application equipment. PMID- 1504498 TI - Effect of DDT on the immune system in Swiss albino mice during adult and perinatal exposure: humoral responses. PMID- 1504499 TI - Comparative effects of potassium dichromate on the mutagenicity of some nitrohydrocarbons and methylating agents. PMID- 1504500 TI - Hematological and biochemical changes in rats administered with Aspergillus niger infested diet. PMID- 1504501 TI - ELISA of simazine in soil: applications for a field leaching study. PMID- 1504502 TI - Investigation of isomer specific polychlorinated biphenyls in printing inks. PMID- 1504503 TI - Implications of physico-chemical factors on the migration of phthalate esters from tubing commonly used for oral/nasal feeding. PMID- 1504504 TI - Copper induced metabolic changes in Sunetta scripta (Bivalvia): oxygen uptake and lactic acid production. PMID- 1504505 TI - Biosorption and degradation of butyltin compounds by the marine diatom Skeletonema costatum and the associated bacterial community at low temperature. PMID- 1504506 TI - Oxadiazon residue concentrations in sediment, fish, and shellfish from a combined residential/agricultural area in southern California. PMID- 1504507 TI - Effects of deltamethrin on the South American toad, Bufo arenarum, tadpoles. PMID- 1504508 TI - Evaluation of head space technique for the determination of trihalomethanes in water. PMID- 1504509 TI - Evaluation of a pentachlorophenol immunoassay for environmental water samples. PMID- 1504511 TI - Carbon filtration of EDB-contaminated well water: a one-year study. PMID- 1504510 TI - Quantification of alachlor in water by a novel magnetic particle-based ELISA. PMID- 1504512 TI - Sorption and leaching of bromacil and simazine in Florida flatwoods soils. PMID- 1504513 TI - Identification of decomposition products of 1,1'-ethylidenebis [L-tryptophan], a compound associated with eosinophilia-myalgia syndrome. PMID- 1504514 TI - Apparent threshold of lead's effect on child intelligence. PMID- 1504515 TI - Maternal toxicity of methacrylonitrile in Sprague-Dawley rats. PMID- 1504516 TI - Metabolic profile of atrazine and N-nitrosoatrazine in rat urine. PMID- 1504517 TI - Effects of daily phosphamidon administration on certain blood biochemical measurements in Bubalus bubalis. PMID- 1504519 TI - Arsenic and copper residues in waterbirds and their food down inlet from the Island Copper mill. PMID- 1504518 TI - Toxic elements and organochlorines in harbor seals (Phoca vitulina richardsi), Kodiak, Alaska, USA. PMID- 1504520 TI - Mancozeb residues on field sprayed apricots. PMID- 1504521 TI - Egg mercury levels decline with the laying sequence in charadriiformes. PMID- 1504522 TI - Methane in well water from Lake Charles, Louisiana. PMID- 1504523 TI - Response of rainbow trout to a two month exposure to Vision, a glyphosate herbicide. PMID- 1504524 TI - Effects of kraft lignin and chlorolignin on the binding and bioavailability of benzo(a)pyrene to Daphnia magna straus. PMID- 1504526 TI - The goose story. PMID- 1504525 TI - Active decision making. PMID- 1504527 TI - Socially responsible travel. PMID- 1504528 TI - [Effects of traditional Chinese medicine and pharmacology on increasing sensitivity and reducing toxicity in tumor patients undergoing radio-chemical therapy]. PMID- 1504530 TI - [Relation of T-lymphocyte subsets and symptom complex groups of patients with chronic aplastic anemia]. AB - The T-lymphocyte subsets of 38 patients with chronic aplastic anemia (CAA) were measured by monoclonal antibody (McAb) and ABC method and the relationship of T lymphocyte subsets and symptom complex groups by traditional Chinese medicine theory were also analysed. It was shown that the T subsets of patients with CAA have remarkable changes: Ts (41.3 +/- 11.2%) increased more than the control (22.9 +/- 4.5%), Th/Ts decreased significantly more than the normal control (0.98 +/- 0.38 to 1.59 +/- 0.38). From the group of deficiency of both vital energy and blood to the group of deficiency of Kidney-yang to the group of deficiency of Kidney-Yin to the group of deficiency of both Kidney-Yang and Kidney-Yin, the Th lymphocyte gradually decreased, Ts lymphocyte successfully increased (from 33.8 +/- 7.9% to 57.7 +/- 7.5%), Th/Ts ratio declined (from 1.29 +/- 0.36 to 0.57 +/- 0.19). The Th/Ts ratio of the latter two groups decreased more than the former two groups (P less than 0.01). These results indicated that the T lymphocyte subsets and symptom complex group of patients with CAA were closely related and when deficient Yang affects Yin the immunologic function of body has a more obvious change. This revealed the connotation of Kidney-Yin and Kidney-Yang on the immuno-regulating cells (T lymphocyte subsets) level. PMID- 1504529 TI - [Correlation between traditional Chinese medicine classification of 53 patients with aplastic anemia and varieties of hemopoietic progenitor cells in vitro culture]. AB - Aplastic anemia can be classified distinctively three types as progenitor depletive; immunosuppressive and androgenic sensitive. Using bone marrow culture in vitro which had been accomplished in our laboratory, 53 patients with aplastic anemia were also classified according to TCM term in three groups as Yin deficiency, Yang deficiency and both Yin and Yang deficiency, and the correlation was observed between TCM classification and lab character of these patients. The results showed that the number of CFU-GM, CFU-E and BFU-E in Yang deficiency group was significantly higher than that in the other two groups (P less than 0.01 and P less than 0.05). It also showed that the sensitivity of progenitor cells to androgenic hormones of Yang deficiency group was preferential to all (P less than 0.005 and P less than 0.05). The percentage of immunosuppressive type of aplastic anemia in Yin deficiency group was much higher than those in the other two groups (P less than 0.005). These observations suggested that TCM classification for aplastic anemia in this paper has objective material foundation. PMID- 1504531 TI - [High dose cinobufocini in attenuation and treatment of infection and granulocytopenia during combined chemotherapy of malignant blood diseases]. AB - The use of high dose Cinobufocini in attenuation and treatment of infection and granulocytopenia during combined chemotherapy was observed in patients with malignant blood diseases. The study was designed in such a way that each patient served as self control. The patients, 18 males and 12 females, aged 16-66 (average 34), 62 experiments in 20 patients with acute leukemia, 8 with malignant lymphoma and 2 with multiple myeloma were observed. In patients with the treatment of high dose Cinobufocini, infection was significantly decreased and the number of granulocytes was not markedly changed before and after the treatment. The observation demonstrated that high dose Cinobufocini can significantly reduce the risk of infection and degree and duration of granulocytopenia associated with chemotherapy of patients with malignant blood diseases. The use of high dose Cinobufocini is simple and convenient and with very little side effects. PMID- 1504532 TI - [Relation between cardiac function and the pulse condition, sphygmogram in patients with hemopathy]. AB - The authors determined the impedance plethysmogram, differentiator (dz/dt), carotid arterial pulse wave, apexcardiogram, electrocardiogram and radial sphygmogram of 106 cases with hemopathy by using a RM-6000 polygraph systems. The results showed that the cardiac function of the patients with hemopathy had obviously been injured. The time of ejecting blood was shortened markedly in the left ventricle. The heart rate increased, total peripheral resistance and cardiac output decreased. These led to the formation of rapid slippery and thready pulse. The formation of string-like pulse is related to the injury of cardiac function and decrease of the arterial compliance. PMID- 1504533 TI - [Pathology of syndrome-differentiation types of superficial deficiencies in patients with gastric cancer]. AB - Analysing the relations between TCM syndrome differentiation type and pathology in 312 patients with gastric cancer, the authors put forward the syndrome differentiation type of deficiency of vitality and excess in superficiality. The studies showed that the four syndrome types of deficiency of vitality such as Spleen-Stomach deficiency, Qi-Xue deficiency, Yin deficiency and inner heat, Spleen-Kidney Yang deficiency and the three syndrome types of excess in superficiality such as Liver-Stomach disorder, blood stasis and stagnation of Qi, Phlegm-dampness and stagnation of toxic. The same changes in pathologic characteristic of both were from early to late stage, the infiltration getting deeper, the tumor getting larger and the metastasis of lymph nodes around the stomach from little to much. Their difference was that in the deficiency of vitality syndrome-type, the chief manifestation was in nest or spread infiltration type which became serious by degrees, whereas in excess in superficiality type, the reaction of lymphoidocytes around the cancer was decreasing. The studies also showed that in most syndrome types of Spleen-Kidney Yang deficiency and Phlegm-dampness and stagnation of toxic, the tumor occurred in wide-range and the degree of tissue differentiation was quite low. The authors suggested that there might be morphopathologic basis in TCM syndrome differentiation types and the conclusion has practical value in guiding clinics. PMID- 1504534 TI - [Antitumor effect of Tripterygium wilfordii]. AB - A new component of antitumor action TG has been isolated from the ethyl acetate extract of Tripterygium wilfordii (besides Triptolide, Tripdiolide and Triptonide). TG was shown in this study to have obvious antitumor effects. The average life span of H22, S180, EAC and breast carcinoma-bearing mice treated with TG ip x 2 days were 100% more than those of the control mice (P less than 0.01) TG was able to inhibit tumor growth of S37-bearing mice at the dose of 150 mg/kg per day, ig x 3, its inhibitory rate was 42% (P less than 0.01). TG could also inhibit squamous epithelial lung carcinoma induced by 3-methylcholanthrene. The inhibitory rate was 65.13% (P less than 0.05). TG had remarkable killing effect on human HL60 and Daudi cells and two direction effects on function M phi of mouse abdominal cavity in vitro. PMID- 1504536 TI - [Development of traditional Chinese medicine and pharmacy in Singapore]. PMID- 1504535 TI - [Effects of Chinese materia medica in activating blood and stimulating menstrual flow on the endocrine function of ovary-uterus and its mechanisms]. AB - Effects of Salvia miltiorrhiza (SM), Ligusticum chuanxiong (LC) and Artemisia anomale (AA) on the endocrine function of ovary-uterus were studied. In immature Wistar rats, SM increased the level of estradiol (E2) in plasma (131.8 +/- 7.4 pg/ml, P less than 0.01), the weight of uterus (35.3 +/- 4.5 mg, P less than 0.05) and the ovarian PGF2 alpha content (495.0 +/- 41.7 pg/ova., P less than 0.05), but the ovarian PGE2 content was reduced (2198.3 +/- 139.0 pg/ova, P less than 0.01), as compared with that in the control (96.6 +/- 3.2 pg/ml, 23.3 +/- 2.6 mg, 339.0 +/- 30.0 pg/ova, and 3840.8 +/- 480.0 pg/ova. respectively). LC and AA had no influence except that they decrease PGE2 content in ovary (2534.8 +/- 351.3 and 2629.7 +/- 290.7 pg/ova). AA decreased the receptor binding capacity for E2 in uterus (P less than 0.05). SM stimulated the ovulation in immature mice pre-treated with PMSG. LC and AA had no significant effect on ovulation. In pseudopregnant rats (with PMSC-hCG), SM, LC and AA all inhibited the function of corpus luteum, decreased the level of progesterone in plasma (11.1 +/- 2.8, 15.5 +/- 2.5, 19.3 +/- 5.6, respectively, 55.4 +/- 5.4 ng/ml in control, P less than 0.01) and hCG/LH receptor binding capacity of ovary (P less than 0.01). In pseudopregnant animals treated with AA, endogenous PGE2 content of ovary (50.2 +/ 2.7 pg/ml ova.) and the formation of PGE2 form AA in vitro in ovary (1765 +/- 166 pg/mg ova.) were reduced. The PGF2 alpha content in uterus was increased.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1504537 TI - [Correlation between Chinese traditional drug Rhubarb and Western medicine]. PMID- 1504538 TI - [Trace elements and hemopoietic system diseases]. PMID- 1504539 TI - Nursing models redundant in practice. PMID- 1504540 TI - Why nurses do not write. PMID- 1504541 TI - Neuropsychopathology of HIV/AIDS. AB - Most, if not all, patients with HIV/AIDS experience significant problems in adjusting to a probably fatal illness and require psychological or psychiatric assistance. This places an enormous neuropsychiatric burden on the psychiatric services. PMID- 1504542 TI - The use of hypochlorite solutions in wound management. AB - Hypochlorite solutions have been an issue of controversy for many years. Research has highlighted their harmful effects and yet doctors and nurses continue to use them. This article will review the literature both for and against the use of hypochlorite solutions and will examine alternative wound dressings. PMID- 1504543 TI - Juvenile chronic arthritis. AB - Juvenile chronic arthritis affects one in a thousand children in Great Britain. This article will outline the acute systemic forms and describe the impact that this condition has on child and family so that nurses may better manage their care. PMID- 1504544 TI - Promoting continence following head injury. AB - Assessment and identification of related problems are crucial in the management of incontinence and the promotion of continence. Assessment checklists and regular recording of incontinence using appropriate charts (toilet charting) help the nurse to diagnose the problems. It is not sufficient just to identify incontinence as the problem; assessment should be much more specific, e.g. identifying problems such as nocturia, nocturnal enuresis, urgency, urge incontinence and polyuria. Planning and implementing care should always promote the optimum level of continence as its final ideal goal. Appropriate and adequate management of any specific aspect/type of incontinence should be considered only if the ideal goal is unachievable. The tools and charts used for assessment are also useful in evaluating the effectiveness of care. Incontinence aids should be chosen only after careful assessment and should be used to lessen the specific problem and help promote continence. They should not be used to encourage continuing incontinence. PMID- 1504545 TI - The nurse as patient educator. AB - This article aims to examine the andragogical theory of adult learning and the implication that knowledge of adult learning theory is a prerequisite for successful patient teaching. PMID- 1504546 TI - A case for continuing education. PMID- 1504547 TI - Primary nursing and the law. AB - All professional nursing activities carry legal implications as nurses owe a legal duty of care to their patients. As primary nursing is being increasingly adopted as a system of organizing care nurses need to be aware of the accountability it entails. PMID- 1504548 TI - How to respond at interview. AB - Interviewers use a wide range of questioning techniques to explore candidates' potential. Understanding the techniques helps the candidate make a response. This is the first of two articles which consider questioning skills and how to respond. PMID- 1504549 TI - Staff support groups: are they necessary? AB - The NHS has the reputation of being a poor provider of emotional care and support for its staff. However, informal data suggest that staff support work is increasing dramatically and is gaining a higher profile on the management agenda. PMID- 1504550 TI - Caring for people with learning difficulties in Czechoslovakia. AB - In June 1992 a massive step forward was made in Czechoslovakia when the first school for people with learning difficulties was opened. This article examines the problems facing this school and the background to its creation. PMID- 1504551 TI - The whistle-blower's charter. PMID- 1504552 TI - Mental health nursing: now you see it, now you don't. PMID- 1504553 TI - Feeding the critically ill patient. AB - Evidence for the active role of the gut in multiple organ failure has turned attention away from total parenteral nutrition back to enteral nutrition as the optimal nutritional support in the critically ill. With proper feeding protocols it is possible to feed enterally the most critically ill patients. PMID- 1504554 TI - Measurement of quality of life for elderly people on dialysis. AB - Renal nurses face certain difficulties when caring for a rapidly increasing population of elderly people. This article examines quality of life and analyses the appropriateness of a self-care philosophy for this group of patients. In addition, the process of adaptation to chronic illness is discussed. PMID- 1504555 TI - Preoperative fasting of patients undergoing elective surgery. AB - Preoperative fasting regimens tend to be based in ritualistic practice causing physical and psychological harm to patients. This research study investigates current nursing practice and concludes that it must be research based. PMID- 1504556 TI - Health visiting in a well-baby clinic. AB - This article highlights the changes that were implemented after research was carried out into health visiting practice in a well-baby clinic. The study was the result of collaboration between practitioners and nurses working in the academic field. PMID- 1504557 TI - Advances in the clinical practice of psychiatric nursing. AB - Understanding mental health needs forms the basis of psychiatric nursing care. Analysis of these needs and knowing what resources are available determines the clinical practice of psychiatric nursing. PMID- 1504558 TI - New Code of Professional Conduct: how it affects you. PMID- 1504560 TI - How to respond at interview: 2. AB - The previous article in this series considered some of the extensive questioning techniques that interviewers use to explore candidates' potential. This article will consider in depth the remaining types of questions used in selection interviews. PMID- 1504559 TI - Accountability in principle and in practice. AB - The United Kingdom Central Council for Nursing, Midwifery and Health Visiting (UKCC) has again declared its position on the subject of accountability by publishing the third edition of its Code of Professional Conduct for the Nurse, Midwife and Health Visitor and a new The Scope of Professional Practice. This article examines what these documents mean for professional nursing practice. PMID- 1504561 TI - Analysis of training needs of qualified nurse practitioners. AB - Training needs analysis is essential in the development of continuing education programmes. This article outlines a study that attempts to identify a systematic approach to the assessment of training needs of qualified nurse practitioners within three separate health authorities. PMID- 1504563 TI - Mental health nursing: getting the message across. PMID- 1504562 TI - Perception of pain management in a hospital in Thailand. AB - After winning the American Medical International Nurse Scholarship Award in 1990, the author went to the Chulalongkorn University Hospital in Bangkok to study how the nurses in the surgical intensive care unit manage patients in acute pain. PMID- 1504564 TI - Educating for collaboration in community care. PMID- 1504565 TI - A critique of the Barthel Index. AB - This article provides a critical review of a popular functional index, the Barthel Index. The strengths and weaknesses of the index with an emphasis on its use by nurses is considered and the need to use this and other functional indices for measuring disability is addressed. PMID- 1504566 TI - A nursing muse. AB - The nursing process and nursing models can obstruct nurses' understanding and prevent them from caring for patients in a personalized way. This article introduces a 'nursing muse' as a way of extending understanding beyond scientific intellectualization. PMID- 1504567 TI - Community care: are we putting all our eggs in one basket? AB - The forthcoming community care legislation due in April 1993 has been adopted largely without criticism. While supporting the general principles underpinning community care this article sounds a cautionary note, highlighting the need to keep appropriate institutional alternatives to retain an element of choice. PMID- 1504568 TI - Developing a community-based leg ulcer clinic. PMID- 1504569 TI - Poverty: a challenge for nursing in the 1990s. AB - How seriously is poverty considered in nursing practice? This article aims to provide an introduction to poverty in the UK today for all nurses, midwives and health visitors. PMID- 1504570 TI - Wound care: how well do you dress? PMID- 1504571 TI - Local research ethics committees and nursing: a critical look. AB - The Department of Health guidelines on local research ethics committees are now in operation. But, are they enforceable and what relevance do they have to nursing? PMID- 1504572 TI - How to choose the right applicant. AB - Appointing staff to a post is a complex process for nurse managers. The cost of failing to select the best person can be high. Careful preparation on the interviewer's part is essential if the selection process is to be effective. PMID- 1504573 TI - Outpatient nurses must adapt to survive. AB - Outpatient nursing has long been considered a clinical backwater. However, recent critical reports, the NHS reforms and other trends in healthcare are likely to change this. Outpatient nurses must move quickly to develop a new role for themselves or the opportunity will be lost. They should aim to make the best possible use of their nursing skills, given that outpatients need nursing care. PMID- 1504574 TI - Healthcare in an Indian hospital. AB - The Hospicio Hospital of Margoa provides a vast array of services that cater for diverse healthcare needs. This article describes what it is like to nurse in an Indian hospital. PMID- 1504576 TI - Morphological aspects of early and late collagen degradation in granulation tissue. AB - A sequential histologic, ultrastructural and immuno pathologic study was carried out in the Selye's inflammatory pouch model to observe extracellular matrix and cellular changes during granulation tissue formation. Besides changes involving different components of the connective tissue, it was observed that collagen resorption occurred under a biphasic process. At an early phase (3rd to 15th day), in which exudative inflammatory changes predominated, signs of collagen synthesis and degradation were seen simultaneously. Extracellular breakdown and internalization of collagen fragments within fibroblasts and myofibroblasts were observed. Later on (30th to 60th day), changes affecting collagen had a different ultrastructural appearance. Collagen fragmentation, focal "lytic" and "electron dense" changes occurred in the extracellular space specially at the periphery of fibroblasts, myofibroblasts and smooth muscle cells. Collagen degradation, thus seems to be a continuous process in granulation tissue, occurring with different morphologies at different times. PMID- 1504575 TI - The ontogenesis of skin and organ characteristics in the Syrian golden hamster. III. Ontogenetic and intraspecific allometry for strain and sex as well as body weight- and age-dependent correlations. AB - The allometric relations, i.e. bodily characteristics, body weight-relationships as well as age-dependent organ and biochemical data were studied in a total of 464 golden hamsters of both sexes of an acromelanic white inbred and agouti coloured outbred strain. In the 3 age sections studied (I = day 1-20, II = day 25 100, III = day 110-365) the body weight- and age-dependent relations were found to be altered between and within the various characteristics. The body weight correlations predominated in the case of organ weights and skin muscle thickness. By contrast, age correlations were seen above all in the skin compartments with cyclic growth, hair follicle density and reticular thickness in the age sections I and II. Papillary thickness showed a positive relation to body weight and age after weaning, but no long-term relations were observed with both plasma insulin and blood glucose levels. The allometric behaviour of skin compartments could be explained particularly by thermoregulatory and "geometric" similarities and that of the organs by metabolic and other similarities. Most sex and strain differences in the absolute data, except for the kidney and adrenal weights, disappeared on allometric analysis and were thus mainly due to differences in body weight. For long-term toxicological investigations, the documentation of age and body weight as well as the determination of ontogenetic allometry is a "must". PMID- 1504577 TI - Studies on quantitative morphology. XIV. Morphometry of connective tissue in normal and cirrhotic rat livers between accuracy and working expense. AB - The percentages of connective tissue in sections of normal and cirrhotic rat livers up to values of about 40% are measured by point counting with net point distances between 160 microns and 5,120 microns. For a test area of about 1 cm2 a suitable distance of 640 microns led to a sufficient number of data for an always acceptable accuracy, therefore the measuring time per organ was not more than 10 min for approximately 250-400 hits. In the case presented the coefficient of variation for 10 repeated measurements decreases from 26.9% for normal livers down to 3.5% for livers with about 40% connective tissue. An enlargement of the net point distance for this test area to 1,280 microns and about 100 or less hits results in higher coefficients of variation and inacceptable differences between the x min and the x max data during a series, which becomes more clear for lower percentages. A further enlargement of the net point distance is accompanied by a further inaccuracy, but an enlargement of the test area allows larger net point distances. PMID- 1504578 TI - Morphometric investigations on endocrine glands. VIII. Karyometry in epithelial cells of thyroid glands during inhibition of lactation by quinestrol. PMID- 1504579 TI - Ex vivo investigation of blood monocyte and platelet behaviour in pigs maintained on an atherogenic diet. AB - Domestic pigs aged 4 months were fed for 16 weeks an atherogenic diet rich in cholesterol and saturated fatty acid. The increase of plasma cholesterol and triacylglycerol levels was found to be accompanied by a significant increase in the number of blood monocytes and platelets when compared to control animals. Furthermore, the atherogenic diet produced a small but significant reduction in the blood monocyte phagocytic capacity and adhesion to plastic surface. No significant differences between both groups were found when spontaneous platelet aggregation in whole blood was studied. However, platelets from pigs fed the atherogenic diet had a smaller mean cell volume compared to controls. The results indicate than an atherogenic diet may affect blood monocytes and platelets in pigs. PMID- 1504580 TI - The male reproductive organs in experimental Chagas' disease. II. Morphometric study of the vas deferens in the chronic phase of the disease. AB - A previous study showed that the vas deferens of mice in the acute phase of Chagas' disease had a slight increase in the muscle layer area associated with a small decrease in the luminal area. The vas deferens of chronic chagasic mice, investigated in the present experiment, presented a marked increase in the luminal area in addition to a significant thinning of the muscle and epithelium layers. The structural alterations of the vas deferens observed in the acute and chronic phases of Chagas' disease were compared with the evolution of chagasic esophagopathy. PMID- 1504581 TI - In vivo changes of heterogeneity of mouse peritoneal macrophages induced by cis diamminedichloroplatinum (II) (cis-DDP) and related platinum compounds. AB - The s.c. injection of cis-DDP into ABD2F1 mice (8 mg/kg b.m.) resulted in alterations of size and surface structure of peritoneal macrophages (PM) and in a reduction of the mean number of Concanavalin A (ConA) binding sites of PM. The PM population of control mice which received physiological saline only consisted of 2 subgroups with a higher and a lower mean ConA binding site number per cell. Contrarily, PM of cis-DDP-treated mice failed the subpopulation with higher ConA binding site number. A loss of this subpopulation was also found in mice treated with platinum salt K2PtCl4 or K2PtCl6. X-ray microanalytically determined elemental contents of PM of control and treated mice showed a correlation between ConA binding site number and cellular concentration of phosphorus or sulphur with the exception of a small group of PM which was characterized by a high content of sulphur and a low number of ConA binding site. This correlation was not found in normal mice. PMID- 1504583 TI - Biology of Bacilli. Applications to industry. PMID- 1504584 TI - Control of postexponential gene expression by transition state regulators. PMID- 1504582 TI - Liver regeneration in partially hepatectomized rats infused with carnitine and lipids. AB - Male Wistar rats were subjected to 65-70% hepatectomy. Immediately after surgery a 6-hour infusion was given containing 115 kJ/kg b.w. of long-chain fatty acids (Nutralipid Spofa) (N) or N combined with L-carnitine (Carnitene Sigma Tau) in doses 8 mg (12.4 mumol), 40 mg (62 mumol) and 200 mg (310 mumol)/kg b.w. The rats were killed 6, 18, 21, 24 and 30 h after surgery. The results of our study demonstrate that infusion of lipids combined with carnitine, has a stimulating dose-dependent effect on liver regeneration in partially hepatectomized rats, excluding the low dose of carnitine--8 mg/kg. The dose of carnitine of 40 mg/kg had the highest stimulating effect on the course of the liver DNA synthesis, culminating 21 h after partial hepatectomy. Later, 24 and 30 h after hepatectomy, the mitotic activity of hepatocytes was highest in rats infused with carnitine in doses of 200 mg/kg b.w. PMID- 1504585 TI - Molecular cloning. PMID- 1504586 TI - Protein export and the development of secretion vectors. PMID- 1504587 TI - Extracellular enzymes: gene regulation and structure function relationship studies. AB - The first conclusion that one could make from the literature covered in this section is that most single mutations in subtilisin BPN'n do not cause major structural alterations. Even multiple mutations, though they may cause local minor perturbations at each of the altered sites, do not affect the overall structure to a large degree. Bott and Ultsch (1986) observed that the subtilisin BPN' structure is very tolerant of single mutations, and this tolerance may have been necessary for survival of the enzyme during the course of evolution. This structural tolerance is not all that surprising if one considers that the structure of subtilisin Carlsberg is very similar to that of subtilisin BPN' while the protein sequences differ by 31%. A superposition of the 274 alpha carbon atoms of the two enzymes gives a root mean square (rms) deviation of 0.053 nm, a value indicating significant structural similarity (McPhalen and James 1988). Furthermore, the fungal enzyme proteinase K, which is classified as part of the subtilisin family, has approximately 38-40% sequence homology with bacilli subtilisins, particularly in the catalytic site and substrate-binding regions (Betzel et al. 1988). For these sequence-homology regions there is also a structural similarity indicated by a least squares superposition of alpha-carbons giving an rms deviation of 0.11 nm (Betzel et al. 1988). Thermitase, also a member of the subtilisin family, has 47% sequence homology to subtilisin BPN' (Gros et al. 1989). If the best 203 alpha-carbon atoms are superposed, then an rms deviation of 0.05 nm is obtained (Gros et al. 1989). Apparently a significant amount of sequence variation still allows for overall structural similarities in the subtilisin family of enzymes. Though the overall structure of subtilisin is not easily perturbed by single or even multiple mutations, it is clear from the evidence reviewed here that single mutations can lead to very significant effects on the catalytic efficiency, substrate preference, and stability of the enzyme. Analyzing the structural alterations in subtilisin mutants will lead to an understanding of the molecular effects of the mutations at the atomic level. This understanding enables investigators to model and predict the effects of other substitutions, and allows them to focus their efforts on those mutants that are most likely to have the desired properties.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1504588 TI - Properties of Bacillus thuringiensis and its intracellular crystal proteins. PMID- 1504590 TI - Useful Bacillus strains and plasmids. PMID- 1504589 TI - Development of genetic engineering in Bacillus megaterium. AB - The opportunities for industrial genetic engineering in several species of Bacillus other than B. subtilis and B. thuringiensis are now becoming a reality. Many species have advantages for certain industrial applications, such as the lack of alkaline proteases, stable plasmid maintenance, and production of thermostable enzymes. It is now possible to increase production levels in many Bacillus strains that are already high producers of amylases, proteases, penicillinases, and penicillin amidases, by the introduction of such genes on high-copy-number plasmids. Possible problems in gene regulation, expression, limits on protein production, and secretion will be encountered, but recent reports on comparisons of expression of bacterial and eukaryotic genes in B. subtilis and B. megaterium (Shivakumar et al. 1989; Donovan et al. 1989a, 1989c; Ginsburgh et al. 1989) suggest that some species may prove to be better expression hosts for specific genes than others. What is needed is extensive comparative studies in promising species to better understand the parameters affecting cloning, gene expression, and protein secretion in the bacilli. In this chapter we have emphasized the development of genetic analysis and rDNA methods in B. megaterium. While the chromosomal map is still not a complete circle, many gene loci have been mapped, some with three-factor crosses, and have been characterized by enzyme assays (leu, trp, hem, cob, cbl) as well as complementation with B. subtilis genes (trp, dnaK, pur, met, ssp) E. coli genes (ATPase), hybridization (spoVG, abrB, sigK, ssp), and by growth on intermediates (trp, leu, thy, gua, ade, pur, pyr, his, arg). A mapping kit of 12 strains is available, and can facilitate the mapping of new mutations rapidly. This is of great advantage in strain construction since genes can be transferred at will by cotransduction. A partial physical map generated by pulse gel electrophoresis is also available (Muse 1990). It remains to be determined whether gene conversion occurs in B. megaterium as it does in B. subtilis. This is a powerful tool for rescuing genes and mutations of interest from the chromosome. There are now over 600 mutants available in our laboratory, over 100 in the laboratory of J.C. Vary, and several more that have been characterized in various laboratories throughout the world. Many of these are available in stock culture collections, although this source needs to be expanded. Mutants that should be useful for genetic engineering include recombination negative, protease negative, and plasmidless wild type, as well as Lac negative and several auxotrophs in the plasmidless background, and many sporulation negative mutants. PMID- 1504591 TI - Standard techniques for Bacillus. PMID- 1504592 TI - Transcriptional regulation of gene expression in Bacillus. PMID- 1504594 TI - Aspergillus: biology and industrial applications. PMID- 1504593 TI - Heterologous gene expression in Bacillus subtilis. PMID- 1504595 TI - New developments in fermented beverages and foods with Aspergillus. PMID- 1504596 TI - Industrial enzymes from Aspergillus species. PMID- 1504597 TI - Early developmental events during asexual and sexual sporulation in Aspergillus nidulans. PMID- 1504598 TI - Expression of foreign proteins in the genus Aspergillus. PMID- 1504599 TI - Mycotoxins: molecular strategies for control. PMID- 1504601 TI - Human pathogenesis. PMID- 1504600 TI - Mycoses and mycotoxicoses of animals caused by aspergilli. PMID- 1504602 TI - United States government regulations affecting aspergilli and their products. PMID- 1504603 TI - Patent protection for Aspergillus-related inventions. AB - Patents are important indicators of trends in biotechnological developments. Patents involving Aspergillus have stimulated growth in bioindustry, particularly in the fermentation and food industries. Patent specifications of Aspergillus related inventions contain a voluminous amount of technical information and scientific data concerning Aspergillus biotechnology. A review of U.S. patents where Aspergillus cultures are cited in the disclosure demonstrates the value and versatility of the fungus. Identifying and evaluating these inventions is one measure of assessing the technical changes resulting from the use of Aspergillus cultures and of helping the industry maintain its innovative edge. PMID- 1504604 TI - Sexual and parasexual genetics of Aspergillus species. PMID- 1504605 TI - Culture collections: sources and management of Aspergillus cultures for biotechnology. PMID- 1504606 TI - Current taxonomic schemes of the genus Aspergillus and its teleomorphs. PMID- 1504607 TI - Control of gene expression in the catabolic pathways of Aspergillus nidulans: a personal and biased account. PMID- 1504608 TI - Protein synthesis in Aspergillus nidulans. AB - In this review of protein synthesis, we have described a system for translation of mRNA using extracts of A. nidulans. This system is useful for characterizing mutants suspected to have defects in protein synthesis and for assessing the toxicity of various antibiotics and their effects on misreading the genetic code. The well developed genetical system of A. nidulans has enabled us to map at least 27 new genes whose mutation disturbs the level of translational accuracy. These mutants could be used to identify new components of translation or new roles for established components. The abundant fidelity mutations themselves could be used to elucidate the mechanism for maintaining the accuracy of protein synthesis. The large number of mutations in the control of fidelity indicate that mutations in other parts of the translation system could be easily obtained. This would be particularly important for initiation where many factors are thought to be needed and yet their exact roles are unknown. A. nidulans appears to have normal eukaryotic ribosomes and translation factors that can be used to study the mechanism of protein synthesis, its regulation, and the maintenance of its high fidelity. If highly purified factors were used, requirements for hitherto undiscovered factors could be seen. Since A. nidulans has typical eukaryotic responses to inhibitors of translation, it could be used to study new inhibitors, their mode of action, and their potency. Among the fungi, A. nidulans could be a worthy competitor to S. cerevisiae in the field of protein synthesis, particularly because so many translation genes have been identified. The system awaits further exploitation. PMID- 1504610 TI - Mammalian genetics. PMID- 1504609 TI - Industrial acids and other small molecules. PMID- 1504611 TI - The human genetic map. AB - The introduction of new technology and increased effort from around the world is driving the completion of the human gene map. In parallel with the creation of the map, we are beginning to see the biomedical benefits that are a direct consequence of learning more about our own genome. PMID- 1504612 TI - CEPH maps. AB - There are CEPH genetic maps on each homologous human chromosome pair. Genotypes for these maps have been generated in 88 laboratories that receive DNA from a reference panel of large nuclear pedigrees/families supplied by the Centre d'Etude du Polymorphisme Humain. These maps serve as useful tools for the localization of both disease genes and other genes of interest. PMID- 1504614 TI - The mouse genome: an overview. AB - A genetic map with one molecularly marked locus per cM will be available for the mouse in the near future. A map of this density should provide molecular reference points that connect genetic and physical maps, identify sites to initiate positional cloning studies for the molecular characterization of mutant loci, and define homologous regions of mouse and human genomes. PMID- 1504615 TI - Genome mapping: cDNA approaches. AB - Clones of cDNAs have several practical advantages as start points for making physical maps of genomes: they are mainly single copy; they expand the map because of the introns in the genomic version of the gene; and they are conserved between species. They also address biologically important regions of the genome. Sequence information helps to identify new gene functions. PMID- 1504613 TI - Integrating maps of chromosome 21. AB - The past year has seen major progress in the construction of various types of maps of human chromosome 21. Perhaps more significantly, the chromosome 21 research community is making very significant progress on integration of these maps through the use of common resources and increased collaboration and communication. PMID- 1504616 TI - The gene for X-linked Kallmann syndrome: a human neuronal migration defect. AB - A new gene from the distal short arm of the human X chromosome has recently been cloned and characterized. Mutations in this gene lead to the neuronal migration defect observed in Kallmann syndrome. Although there is no direct proof for the involvement of this gene in neuronal migration, significant similarities between its predicted protein product and neural adhesion molecules have been found. X linked Kallmann syndrome represents the first example in vertebrates of a neuronal migration defect for which the gene has been isolated. PMID- 1504617 TI - Molecular genetics of the fragile-X syndrome: a novel type of unstable mutation. AB - Fragile-X syndrome, the most common inherited form of mental retardation, has a very unusual mode of inheritance. The disease is caused by a multistep expansion, in successive generations, of a polymorphic CGG repeat localized in a 5' exon of FMR-1, a gene of unknown function. Two main mutation types have been categorized. Premutations are moderate expansions of the repeat and do not cause mental retardation. Full mutations are found in affected individuals and involve larger expansions of the repeat, with abnormal methylation of the neighboring CpG island. The full mutations demonstrate striking somatic instability and extinguish expression of FMR-1. Premutations are changed to full mutation only when transmitted by a female with a frequency that increases up to 100% as a function of the initial size of the premutation. Direct detection of the mutations provides an accurate test for pre- and postnatal diagnosis of the disease, and for carrier detection. A similar unstable expansion of a trinucleotide repeat occurs in myotonic dystrophy. PMID- 1504618 TI - Beckwith-Wiedemann syndrome, tumourigenesis and imprinting. AB - The concurrent development of cytogenetic, clinical, genetic and molecular studies has led to the recognition that the different hereditary and non hereditary forms of the Beckwith-Wiedemann syndrome and associated tumours result from an imbalance between maternal and paternal alleles. The most exciting development in the past year was the discovery of uniparental paternal disomy and the increased understanding, arising from studies in the mouse and in hereditary cases, of the role possibly played by imprinting and somatic mosaicism in partial and complete expression of this complex syndrome. PMID- 1504619 TI - Mammalian X-chromosome inactivation and the XIST gene. AB - X-chromosome inactivation is a unique developmental event that results in the cis limited transcriptional inactivation of most genes on one of the two X chromosomes in female mammals. Studies in both human and mouse have demonstrated that X inactivation requires the presence in cis of a locus, the X-inactivation center, that is thought to be involved in the initiation and/or spreading of the inactivation signal in early development. Identification and characterization of a gene, XIST, which is located at or near the X-inactivation center and which is expressed specifically from the inactive X chromosome in both humans and mouse, suggests that it may be involved in X inactivation. PMID- 1504620 TI - Prion diseases. AB - There have been remarkably rapid advances in the understanding of prion diseases over the past year. The controversial notion that the transmissible agent may be an abnormal isoform of a host-encoded protein, the prion protein, is now gaining wide acceptance. The conundrum of how a disease can both be inherited as an autosomal dominant condition and also be experimentally transmissible by inoculation is beginning to make sense. PMID- 1504621 TI - Mutations in signal transduction pathways and inherited diseases. AB - Intracellular signal transduction pathways have central roles in processes such as growth, differentiation, neurotransmission and development. The aberrant expression of components of various signal transduction pathways has profound consequences for cellular functions. Recent findings indicate that many cases of neoplasia and inherited diseases have, at their roots, mutations in key steps of signalling pathways. PMID- 1504622 TI - Molecular genetics of inherited retinal degenerations. AB - There has recently been substantial progress in categorizing the vast range of human retinal degeneration phenotypes. A molecular approach has assigned chromosomal locations for approximately a dozen such diseases and has identified four of the genes involved. PMID- 1504623 TI - The olfactory multigene family. AB - A novel multigene family has been identified that is likely to encode odorant receptors on olfactory sensory neurons. Further studies on this gene family are likely to shed light on the molecular mechanisms underlying information coding in the mammalian olfactory system. This review is also published in Current Opinion in Neurobiology 1992, 2:282-288. PMID- 1504624 TI - Diabetes mellitus. AB - Developments on four fronts have contributed to an exciting year for the study of diabetes. These include advances in molecular genetic mapping, analysis of animal models of disease, understanding of disease phenotype, and the extension of statistical methods to the study of complex, non-Mendelian traits. PMID- 1504625 TI - Mammalian artificial chromosomes. AB - A mammalian artificial chromosome would enable analysis of the cis-acting DNA sequences necessary for mammalian chromosome function and would allow large numbers of genes in a defined sequence environment to be introduced into experimental animals, agricultural livestock or human cells. Recent technical progress suggests that a route to mammalian artificial chromosome construction is now open. PMID- 1504626 TI - The Y chromosome as a tool for studying human evolution. AB - The use of the Y chromosome in human evolutionary research has only recently begun to gain momentum, partly because of a paucity of polymorphism. Differences in male/female behaviour patterns and the unique mode of inheritance of the Y chromosome also complicate interpretation of the data on Y chromosome variation. PMID- 1504627 TI - The MHC: relationship between linkage and function. AB - It is intriguing that several genes with associated functions, including all of class I and class II genes, as well as some genes affecting antigen presentation of both class I and class II pathways, are linked in the MHC. Recent observations have led to speculation that there may be a functional explanation for keeping these related genes together. PMID- 1504628 TI - An overview of developmental genetics in mammals. AB - Publications in mammalian developmental genetics during the past year reflect a shift of emphasis from the phenotypic level to the primary level of gene expression and the nature of the gene product. A result of this, the developmental role of a considerable number of regulatory genes and specific gene sequences have been identified. The cell type-specific effects of several mutations analyzed in the past have been correlated with effects on growth factors and signal transduction pathways. Specific gene sequences such as those containing the homeobox domains and paired-box sequences have recently been implicated in the control of pattern formation and positional information. PMID- 1504629 TI - Mammalian genetics. PMID- 1504630 TI - The petroleum industry and the public health debate over petroleum products. PMID- 1504632 TI - Physical and mathematical simulation of gasoline component migration in ground water systems. AB - Results are presented from a research study examining the transport and fate of gasoline components in ground water systems. A two-phased modeling approach is described: first, physical laboratory pilot scale models of aquifer systems are constructed and second, mathematical models are constructed to simulate the data generated in the laboratory studies. In general, single-component batch studies overpredicted the degree of retardation shown by multi-component column experiments. PMID- 1504631 TI - Assessing total exposures to gasoline vapor using the source exposure model. AB - Recent developments in source apportionment modeling of volatile organic compounds (VOCs) include receptor modeling (RM) applications to "total" (indoor and outdoor) exposure assessment for source of VOC. Source fingerprints are available for major VOC sources such as gasoline vapor, automobile exhaust, refinery emissions, cleaning solvent vapors, printing inks, and waste-water treatment facilities. The relative proportion of each VOC species in the source fingerprint enables the RM method, through a least squares analysis, to identify each source's presence and quantify its contribution to ambient air concentrations. Sampling periods and locations may be selected to represent microenvironmental exposures. Receptor modeling has direct applicability to determining the relative contribution of gasoline vapors to VOC exposures in the general population. PMID- 1504633 TI - Exposure assessment as applied to risk characterization. A summary report of work group IV. PMID- 1504634 TI - General summary and recommendations of the workshop on general population exposures to gasoline. PMID- 1504635 TI - Gasoline and vapor exposures in service station and leaking underground storage tank scenarios. AB - Exposure to gasoline and gasoline vapors from service station operations and leaking underground storage tanks is a major health concern. Six scenarios for human exposure were examined, based primarily on measured air and water concentrations of total hydrocarbons, benzene, xylenes, and toluene. Calculated mean and upper limit lifetime exposures provide a tool for assisting public health officials in assessing and managing gasoline-related health risks. PMID- 1504636 TI - Stages of change for smoking cessation among former problem drinkers: a cross sectional analysis. AB - Recent research suggests that problem drinkers are less successful in quitting smoking. Stages of change, decisional balance, and self-efficacy measures were used to assess readiness for smoking cessation in a cross-sectional sample of former problem drinkers who were current smokers. As was expected, a very high percentage of recovering problem drinkers had been or currently were regular smokers. Distributions across the stages of change and relationships between stages and decisional balance in this problem drinker sample was found to be similar to results from more general smoking populations. Of those who had quit both smoking and alcohol, 62% quit drinking before or at the same time as smoking (53% before; 9% simultaneous). Those who quit drinking before or at the same time as smoking were characterized by a more problematic alcohol history. A stages-of change perspective with this group is discussed, as are new avenues for future research with such populations. PMID- 1504637 TI - Parental history of alcoholism and probability of marriage. AB - Personal interview data for 16,795 U.S. adults 18-39 years of age were analyzed to assess the effect of positive parental history of alcoholism on the probability of ever having been married. The data were collected as part of the 1988 National Health Interview Survey. The effects of parental history were estimated using logistic regression models that adjusted for age, race, gender, and respondent history of alcohol problems. Nonblack adults who lived with one or more alcoholic parents when growing up were 50% more likely ever to have been married than those with no parental history. The effect was of the same magnitude regardless of whether the alcoholic parent was the mother or the father, but was larger if both parents were reported to be alcoholics. Among blacks, positive parental history of alcoholism did not affect the odds of marriage. The greater likelihood of early marriage among children of alcoholics may help explain their excess risk of marital disruption. PMID- 1504638 TI - Effects of nicotine on subjective arousal may be dependent on baseline subjective state. AB - The often disparate and contrasting effects of nicotine on subjective arousal in smokers may be due in part to differences in presmoking subjective state. In Study 1, on each of 2 days, 10 male smokers were divided into high- and low baseline subgroups on the basis of median split of resting predrug baseline subjective arousal. Then, subjects received intermittent nicotine (15 mu/kg) or placebo via measured-dose nasal spray, with drug conditions counterbalanced between days. In Study 2, 32 male and female smokers were similarly divided into high- and low-baseline subgroups on subjective arousal prior to either smoking or sham-smoking (n = 16 each) during a single session. Results were virtually identical between studies in showing that subjective arousal responses to nicotine (Study 1) or smoking (Study 2) were significantly inversely related to baseline arousal level; those initially low in arousal showed large increases following nicotine or smoking whereas those high in arousal showed little change. No such baseline dependency of responses was seen following placebo or sham smoking. Baseline dependency of cardiovascular responses to nicotine or smoking was also evaluated in similar fashion to determine generalizability of these effects to nonsubjective responses. In each study, systolic blood pressure response was related to baseline level but there was no effect of baseline level on heart rate and diastolic blood pressure responses. Implications of these results for explaining differential rewarding effects of smoking are discussed. PMID- 1504639 TI - Relationship of Tridimensional Personality Questionnaire scores and smoking variables in female and male smokers. AB - The Tridimensional Personality Questionnaire (TPQ) was developed by Cloninger (1986) to measure heritable variation in three patterns of response to environmental stimuli: novelty seeking, harm avoidance, and reward dependence. Cloninger (1987) used the TPQ to identify two types of alcoholism: Type 1 (low novelty seeking, high harm avoidance and reward dependence; both male and female) and Type 2 (high novelty seeking, low harm avoidance and reward dependence; predominantly male). To determine whether characteristic patterns exist in smokers, we administered the TPQ to 119 female and 121 male smokers, along with the Fagerstrom Tolerance Questionnaire (FTQ, a measure of nicotine dependence), the Russell Motives for Smoking Questionnaire (RMSQ), and the Spielberger State Trait Anxiety Inventory (STAI/trait). Compared with a normative sample, our sample exhibited elevated scores on the Novelty-Seeking scale; female smokers were somewhat overrepresented in the highest quartile of the Harm-Avoidance scale; both genders tended to be clustered in the lower quartiles of the Sentimentality-Attachment-Dependence subscale of the Reward-Dependence scale and in the highest quartile of the Persistence subscale. Female smokers showed a significant positive association between Harm Avoidance and FTQ scores, and Harm Avoidance was positively correlated with several RMSQ factors (including Additive smoking) in both genders. These findings suggest that the likelihood of becoming a smoker may be a function of novelty seeking and reward dependence, whereas degree of dependence or addiction once the habit is entrained may be linked to harm avoidance. Our observations establish the potential utility of the TPQ as a tool for examining environmental and heritable variation in smoking behavior and may contribute to improved strategies for prevention and treatment of smoking. PMID- 1504640 TI - Patterns of alcoholism inheritance. AB - Like many other common, complex disorders, alcoholism tends to run in families. Evidence from animal studies as well as biochemical, electrophysiologic, and personality studies of alcoholics and their offspring indicate the existence of heritable factors predisposing to the development of alcoholism. Twin and adoption studies also support the idea that vulnerability to alcoholism depends in part on genetic factors. The observed inheritance, however, does not fit any simple pattern, indicating a substantial degree of etiologic heterogeneity in the alcoholism phenotype, with the ultimate manifestation of the disorder dependent on poorly understood gene-environment interactions. Efforts to address these issues, including the hunt for biological markers, defining more homogeneous subtypes of alcoholism, and molecular genetic strategies of potential use in alcoholism are reviewed. PMID- 1504641 TI - The association of drinking levels and drinking attitudes among Japanese in Japan and Japanese-Americans in Hawaii and California. AB - This study examined cross-cultural differences in drinking attitudes and drinking levels and their correlation among Japanese in Japan and Japanese-Americans in Hawaii or California. In most situations, an increase in drinking levels was associated with more tolerant drinking attitudes in all three groups. Abstainers were less likely to say that getting drunk is sometimes all right, whereas the reverse was true for heavier drinkers. Drinking levels among Japanese, especially among Japanese women, were not highly associated with how much drinking was perceived as acceptable in each situation, whereas among Japanese-Americans, drinking levels were highly associated with drinking attitudes. Although the Japanese had generally tolerant attitudes toward drinking, they indicated higher abstention rates before driving than Japanese-Americans regardless of their drinking levels. This may reflect the impact of public education on drunken driving in Japan. PMID- 1504642 TI - Pediatricians' perspectives on fetal alcohol syndrome. AB - Since the identification of fetal alcohol syndrome (FAS) in 1973, significant inroads have been made towards understanding the effects of alcohol on fetal development. However, it is not clear if these findings are considered clinically relevant by pediatricians. This survey was designed to assess clinical knowledge, practice, and attitudes concerning alcohol-related birth defects. Data were collected in a questionnaire that was mailed to 234 randomly selected Massachusetts pediatricians. Responses suggest that a substantial proportion of pediatricians have knowledge about the effects of alcohol on pregnancy. However, many considered themselves unprepared to deal with this topic. More physicians suspected FAS/FAE than made the diagnosis. Almost three fourths reported they would find professional education in this area helpful. Broader dissemination of research findings in clinically relevant formats and improving the sense of preparedness among pediatricians have the potential to improve the care of children born to heavily drinking pregnant women. PMID- 1504643 TI - Effects of fasting on responses to intravenous fentanyl in healthy volunteers. AB - The effects of food deprivation on the subjective, psychomotor, and physiological responses to intravenous fentanyl (50 micrograms/70 kg) were studied in 6 healthy male volunteers. A randomized, placebo-controlled, crossover design was used in which subjects were injected with fentanyl or saline after either 2, 12, or 24 hours of fasting. Subjects completed several subjective effects questionnaires as well as psychomotor tasks prior to, and at regular intervals, following the intravenous injection for a 3-hour period. An observer-rated behavioral checklist was completed at regular intervals during the session and several physiological measures (including measurement of pupil size) were recorded. Fentanyl induced opiate-like mood changes, miosis (pupil constriction), and impairment of extraocular muscle control, and 4 of the 6 subjects reported liking the effects; however, fasting had no impact on any of fentanyl's effects. We conclude that food deprivation up to 24 hours does not alter the subjective, psychomotor, or physiological response to the opiate, fentanyl. PMID- 1504644 TI - Gender issues in the treatment of abusers of alcohol, nicotine, and other drugs. AB - This review considers gender issues in the recent literature for alcohol, nicotine, and other psychoactive drug abuse and for each of the three drug types reports: (1) the ratio of men to women treated; (2) gender differences in treatment outcome; (3) whether the senior author's gender is related to the gender ratio of subjects in studies; and (4) the percentage of studies reporting methodological variables by gender (e.g., dropouts, outcome). No evidence for sex differences was obtained for any drug class. However, despite the recognized importance of gender as a treatment variable, the majority (72%) of studies failed to address gender differences in treatment outcome. PMID- 1504645 TI - Post-RN degree program curriculum review. PMID- 1504646 TI - Clinical advancement programs. PMID- 1504647 TI - Continuing education is for everyone! PMID- 1504648 TI - Adapting to change: 30 years of nursing. PMID- 1504649 TI - Free choice of life styles for the aged. PMID- 1504650 TI - Life style and environment. PMID- 1504651 TI - [The secular trend of standing height in adolescent girls from longitudinal data]. AB - In this study which is based on the longitudinal data aggregated from health examination records, the subjects consist of 287 girls who attended a private school in Tokyo. The subjects are divided into five groups according to birth year from 1950 to 1970 in order to find secular trend during twenty years with one-way analysis of variance. Age at Peak Height Velocity (APHV), Peak Height Velocity (PHV) and Height attained at Peak Height Velocity (HPHV) were computed in each height velocity curve derived from differential calculus of height distance curve. The result show that HPHV is gradually getting taller by year although APHV and PHV do not change. It may be considered that our subjects of the private school are girls of families in the relatively upper-middle class. PMID- 1504653 TI - [The curriculum and teaching of basic nursing skills in four baccalaureate nursing programs in the U.S.A]. PMID- 1504652 TI - [A survey on the graduates of the baccalaureate program who elected the midwifery course at St. Luke's College of Nursing]. AB - A survey was conducted on the Midwifery Graduates (MG) at the college. 244 students completed midwifery course from 1968 to 1990. The questionnaire was sent to 229 whose address were known, and 133 were responded. The questionnaire consists of demographic data, engagement status with job, expectation to the job, attitude toward the job, and comment on the midwifery course. The results of this study were compared with the study done on the all graduates from 1968 to 1984 at the same school in 1984. As a result, among MG it was shown high rate of higher degree holders and higher in engagement with job. Rate of job holders decreased in the period of childbearing and childrearing, which was similar to the '84 study. But higher in MG who kept their job after marriage. MG who are working in the area of maternal-infant nursing at the time of study, the highest number were being in the clinical nursing, and in the teaching next. The shorter the period from graduation, more number in clinical area, and those who staying in job longer, they were more in either teaching or community nursing area. Among all the subjects worked maternal-infant nursing area, the length of experience as a clinical nurse was approximately 4 years, and it as a teacher was approximately 3 to 4 years. 30 percent of clinical nurse in the maternal-infant nursing, later moved to teaching area. Those who have left their job for personal reasons or earning higher degree, most of them took the job in the area of maternal-infant nursing again. Among MG who were out of job, the rate of willing to return to job were similar to the '84 study.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1504654 TI - The separation of human cord blood by density gradient does not induce a major loss of progenitor cells. PMID- 1504655 TI - International bio-library: quality--safety. PMID- 1504657 TI - Retroviral-mediated gene therapy--safety considerations and preclinical studies. AB - Retroviral mediated gene transfer (1) is now a clinical reality, with several protocols being conducted. The features that have made these vectors appropriate for the first clinical studies in humans are (i) they are derived from well characterized murine retroviruses (ii) many foreign genes have been expressed in many different cell types, and transduction efficiency can be very high (iii) helper or wild type virus free vectors can be obtained in good titer and (iv) the number of sites of proviral integration is limited although the site of integration in the genome is random. Most of the work described has been conducted in the laboratories of our collaborators, notably Drs. W. French Anderson, R. Michael Blaese, Steven A. Rosenberg, and Arthur W. Nienhuis at the National Institutes of Health, Bethesda, MD, and Dr. Malcolm K. Brenner at St. Jude's Hospital in Memphis, as well as work conducted at Genetic Therapy, Inc. But it is very important to appreciate that retroviral vectors themselves were developed from the pioneering work of researchers in a large number of laboratories in the early and mid 80's. PMID- 1504656 TI - Cell targeting by murine recombinant retroviruses. AB - Cell targeting by murine retroviruses carrying recombinant genes would have numerous applications such as immortalization of under-represented cell types from complex cellular mixtures, increasing therapeutical yields in the case of gene therapy and delivery of specific genes at any location and at any moment of the life-time of living animals. To this aim, we are currently developing techniques that allow binding of viral particles to specific cell membrane markers different from the natural receptors. We have shown that biochemical bi specific molecular adaptors able to bind both viral particles and cell surface molecules may reveal appropriate for piloting viruses toward specific cell types. More recently, we have undertaken the genetic engineering of the retroviral envelope glycoprotein in order to modify its natural tropism. This approach is discussed below. PMID- 1504658 TI - Feasibility of adenovirus-mediated gene transfer in vivo. AB - We have evaluated the use of Adenovirus as a new vector for gene transfer in vivo. The capacity of this virus to express a foreign gene even in the absence of viral and cellular replication makes it attractive to deliver a gene to quiescent cells. We show here that organs like lung, liver and muscles are relevant to this strategy. PMID- 1504659 TI - A normal level of beta-globin expression in erythroid cells after retroviral cells transfer. PMID- 1504660 TI - Transduction and culture of purified hemopoietic progenitor cells. PMID- 1504661 TI - p53 as a potential target in cancer therapy. PMID- 1504662 TI - Prospects for tumour therapy using gene transfer. PMID- 1504663 TI - IL-2 gene transduction in malignant cells: applications in cancer containment. PMID- 1504664 TI - The tumor-cytokine transplantation assay and the antitumor activity of interleukin-4. PMID- 1504666 TI - Cell-cell matrix and cell-cell interactions during hematopoietic differentiation. PMID- 1504665 TI - Clinical application of intrauterine bone marrow transplantation for treatment of genetic diseases--feasibility studies. AB - Intrauterine bone marrow transplantation (BMT) may represent a new approach for correction of a large variety of genetic disorders in utero. The procedure may become feasible for more genetic disorders in the future, since a large majority of potentially correctible diseases can be diagnosed at an early stage of gestation in utero using molecular probes that permit analysis of small biologic samples and even few cells that may be obtained by chorionic villi biopsy and/or amniocentesis. Haploidentical paternal marrow (2 cases) and sibling bone marrow cells from a disease-free family members, were infused into the fetus. GVHD was avoided following in vitro T-lymphocyte depletion using monoclonal antilymphocyte (CDW52) antibodies (Campath-1) without affecting stem cell viability, similarly to the procedures in routine use in clinical BMT programs in man. Three women underwent intrauterine BMT at 34, 23 and 25 weeks of gestation for metachromatic leucodystrophy (Arylsulfatase A deficiency, 2 cases) and beta thalassemia major (1 case), respectively. A total of 33 x 10(8), 30 x 10(8) and 30 x 10(8) bone marrow cells were infused intraperitoneally (1 case), intraportally plus intraperitoneally (2 cases) with no fetal distress. Although the procedure was uneventful and no clinical evidence of GVHD was observed following delivery, correction of the basic disorders was not accomplished because of anticipated rejection of marrow allografts.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1504667 TI - Hematopoiesis in the human yolk sac: quantitation of erythroid and granulopoietic progenitors between 3.5 and 8 weeks of development. AB - In a first attempt to investigate the regulation of the early steps of human embryonic hematopoiesis, we measured the number of erythroid and granulopoietic progenitors in 38 human yolk sacs and 15 embryonic livers between 27 and 62 days of development. Both erythroid and granulopoietic progenitors were identified in the yolk sac as soon as 27 days, while in the embryonic liver significant numbers were not observed before 40 days. In the yolk sac, the number of granulopoietic and/or macrophagic progenitors was significantly negatively correlated with gestational age. Such a correlation was not observed for CFU-E and BFU-E, even though in the youngest (less than 30 days) and the oldest embryos studied (greater than 40 days), the number of BFU-E was clearly lower. PMID- 1504668 TI - Cell trafficking and early ontogeny of human lymphopoietic progenitor cells. PMID- 1504669 TI - Embryonic stem cells. PMID- 1504670 TI - The bare lymphocyte syndrome. AB - The bare lymphocyte syndrome is a combined immunodeficiency resulting from the lack of expression of either class I or class II HLA antigens at the cell surface. The main clinical manifestations are infections of the respiratory or the digestive tract. The immunodeficiency involves the absence of antibody formation and the absence of cell-mediated response, to specific antigen, contrasting with virtually normal transplant immunity to allogeneic determinants. The responsible gene(s) is not born by chromosome 6. The best treatment appears, at the present time, to be in utero stem cell transplantation into the sick fetus, and it may, in the future, be gene therapy. PMID- 1504671 TI - HLA 1992: perspectives in bone marrow transplantation. PMID- 1504672 TI - Characterization of lymphocyte subpopulations in cord blood. AB - 27 cord blood samples from healthy newborns were processed according to a "whole blood" flow cytometric analysis. The CD3-positive T cells are characterized by their variability: 44.8 +/- 13.3% of lymphocytes with a lower expression of the gamma delta T cell receptor. The majority of the CD3+ cells are CD38+. Newborn T cells have less ability than adult T cells to express IL-2 receptors as well as HLA-DR. The CD4-positive T cells are equal to 31.0 +/- 10.8% of lymphocytes with a great prevalence of the CD4+/CD45RA+ population. The CD3+/CD8+/CD11b+ cells are increased to 23.4 +/- 7.1% of lymphocytes. The CD57 antigen is not expressed. The NK population, CD16+/CD56+ is increased to 25 +/- 11% of lymphocytes. 68% of CD19+ cord blood B lymphocytes coexpressed CD5. Thus the "suppressive" and "naive" cells are prominently represented in cord blood. PMID- 1504673 TI - Growth and maturation requirements of human B cell precursors. AB - The present study describes our efforts to induce the proliferation of human B cell precursors (BCP). Committed BCP (CD10+, sIgM-) isolated from fetal bone marrow (18-25 weeks) were induced to proliferate at low levels in the presence of IL7. IL3 potentiated this effect of IL7 on BCP, while IL4 partially inhibited this proliferation. However, neither of these cytokines allowed the emergence of mature B cells. The growth of BCP was strongly potentiated by the presence of an adherent fibroblastic bone marrow stromal layer devoid of cells of hematopoietic origin. Addition of IL7 to such cocultures further increased BCP proliferation. BCP were shown to proliferate as stroma-adherent and non adherent cells. Total cell numbers expanded during 3 weeks, as much as 8 fold in the presence of IL7 when compared with input BCP numbers. Finally, BCP remained sIgM- in stroma dependent cultures, and only a subpopulation of cells became CD20+ in the presence of IL7. Our present study demonstrates the feasibility of human BCP expansion in vitro. However, the signals required for the transition of BCP to mature B cells remain to be determined. PMID- 1504674 TI - Fetal liver cell transplantation in various murine models. AB - Allogeneic fetal liver cell transplantation has been shown to be able to reconstitute lymphopoietic systems of mice when these systems are defective or destroyed. Lethally irradiated mice or mice with inherited severe combined immunodeficiency disease (SCID) were grafted with 14 days gestation allogeneic fetal liver cells, then subjected to a follow-up for the immune tolerance to the donor and the normal or subnormal immune reconstitution allowing prevention of diabetes in NOD mice or cure of leukemia in AKR mice and of immunodeficiency in SCID mice. Briefly, when normal CBA mice were lethally irradiated and then grafted with allogeneic fetal liver cells from Balb/c mice, a specific immune tolerance was induced to donor skin grafts. Unrelated skin grafts were rejected and a response to antigens was observed in these chimeras. However, despite the capacity to develop hyperacute rejection of skin allografts, following hyperimmunization, these chimeric mice did not produce anti-H2 cytotoxic antibodies. In SCID mice (CB17), the immune reconstitution occurred when mice were grafted with allogeneic (C57/B16) as well as with syngeneic fetal liver cells. Human cells were found in SCID mice following implantation of human fetal liver and thymus cells. When NOD mice were irradiated, then grafted with allogeneic fetal liver cells, a large part of donor cells were found in NOD recipients, correlating with a low incidence of diabetes. Leukemic AKR mice grafted with allogeneic fetal liver cells had virtually no leukemia relapse, suggesting a strong graft-versus-leukemia effect following such a transplant. PMID- 1504675 TI - Human embryo as a source of cells. PMID- 1504676 TI - Nursing interventions for children with attention-deficit hyperactivity disorder. AB - Attention-deficit hyperactivity disorder frequently coexists with a variety of psychiatric and developmental disorders of child psychiatric inpatients. The author highlights characteristics of these patients and examines nursing contributions to treatment. She emphasizes issues of medication administration and monitoring, as well as the development and implementation of interventions to decrease disruptive behavior, enhance self-control, and develop social skills. Effective management techniques are supported by research evidence and illustrated by case examples. PMID- 1504677 TI - Psychotherapeutic interventions with brain-injured children and their families: I. Diagnosis and treatment planning. AB - Children who suffer brain injuries are at high risk for the development of psychiatric disorders. Using a case study of a healthy, well-endowed boy who suffered a serious brain injury in early childhood, the author highlights typical psychological problems encountered in these children and their families and describes psychotherapeutic issues in diagnosis and treatment planning. PMID- 1504678 TI - Psychotherapeutic interventions with brain-injured children and their families: II. Psychotherapy. AB - Drawing on the case of a boy who was treated in an expressive psychotherapy process in childhood and followed for more than 15 years, the author explores a number of critical issues in the literature on psychotherapy with brain-injured children. These issues include: (1) the efficacy of psychotherapy with neurologically impaired children, (2) its relationship to other modes of treatment, (3) the nature of the therapeutic process, (4) the role of concomitant work with parents in treatment, and (5) the importance of follow-up contacts. PMID- 1504680 TI - Learning disabilities in children with borderline personality disorder. AB - Children with borderline personality disorder are known to have a variety of school problems, including low achievement. Clinicians working with these youngsters have estimated that one third or more may be learning disabled; however, no empirical studies have confirmed these estimates. The author reports the results of a study of 56 hospitalized borderline children in which score profiles from academic and cognitive measures were cluster analyzed. She examines the incidence of independent learning disabilities as well as subgroup membership, and discusses implications for treatment. PMID- 1504679 TI - Headlock: psychotherapy of a patient with multiple neurological and psychiatric problems. AB - Psychodynamic psychiatrists seldom engage in psychotherapy with brain-injured patients because psychodynamic treatment typically depends on the patient's highly developed verbal skills, reflectiveness, tolerance of frustration, and capacity for abstract thinking and generalization--characteristics impaired by brain injury. The author describes the difficult but successful extended treatment of a young adult patient with preexisting attention-deficit hyperactivity disorder and personality disorders who had also abused alcohol and drugs and had suffered severe brain trauma. Treatment was characterized by a lengthy developmental process, the success of which depended on several factors, particularly the maintenance of the therapeutic alliance. PMID- 1504681 TI - Transactions of the Topeka Psychoanalytic Society. PMID- 1504682 TI - Excised human tissues: seek the truth or burn the evidence? PMID- 1504683 TI - Transtracheal oxygen catheters. AB - Transtracheal oxygen catheters enable oxygen to be delivered directly into the trachea without the need for a facemask or nasal cannula. They reduce oxygen requirements by approximately 50% and are, therefore, particularly useful when a portable oxygen system is required. These devices are also indicated in selected patients receiving long-term oxygen treatment. PMID- 1504684 TI - Active management of infertility. AB - Management of infertility is slow, time consuming and, paradoxically, costly. It needs to be streamlined so that diagnosis and management go hand in hand with proper division between primary physicians at district level and highly trained specialists at regional level. Incorporation of assisted conception techniques is the key to the success of such an approach. PMID- 1504685 TI - Shared diabetic care. AB - Increased diabetic mini-clinic activity in general practice offers an unparalleled opportunity to spread the net of integrated care. Important lessons from results of published schemes must, however, be applied to harness the new energy and resources for maximum patient benefit. PMID- 1504686 TI - Uses of labelled white cells. AB - In addition to an established clinical role, labelled white cells have great potential for clinical research. This review will therefore outline the clinical use of labelled white cells and briefly consider their contribution to developments in clinical science. PMID- 1504687 TI - Haemophilus influenzae type b vaccines. AB - Haemophilus influenzae type b (Hib) is a major cause of serious infections in childhood. New vaccines have been developed which are effective in invoking immunity against this organism when administered to children of all ages, including young infants. Their widespread introduction in the UK should lead to a dramatic decline in the incidence of Hib disease. PMID- 1504688 TI - Fluid balance in severe pre-eclampsia. AB - Women with severe pre-eclampsia are at high risk of pulmonary oedema, especially 12-24 hours postdelivery. Effective vasodilatation with fluid restriction and early diuretic therapy are the cornerstones of preventative therapy. PMID- 1504689 TI - Terminology and truth. PMID- 1504690 TI - Cholesterol measurement in high-risk patients. PMID- 1504691 TI - ECG vital during tachycardia termination. PMID- 1504692 TI - HRT and breast cancer. PMID- 1504693 TI - Effects of childhood sexual abuse on adult mental health. PMID- 1504694 TI - Role of cardiotocography. AB - The cardiotocograph (CTG) is a composite record of fetal heart rate and uterine activity. During pregnancy, the CTG is a diagnostic test of fetal condition whenever acute or chronic complications arise. In labour, the CTG provides a continuous indication of fetal response to uterine contractions and interventions. PMID- 1504695 TI - Quality of life during treatment for cancer. AB - Assessment of quality of life produces a hard outcome measure of treatment which allows us to tailor therapy to the patient's needs. This article look at ways in which quality of life can be measured and at its clinical importance in the treatment of cancer. PMID- 1504696 TI - Doctors, confidentiality and the law. AB - Doctors risk erasure from the register and legal action by breaching patients' confidentiality. They should be aware of the instances in which it is legally acceptable. PMID- 1504697 TI - MRCP (Paeds) exam: the present and the possible future. AB - In this article I will give some general advice on how to prepare for the MRCP (Paeds) exam and outline the exam's present structure. I will also discuss the changes that may occur subsequent to the proposed establishment of a college of paediatricians. PMID- 1504698 TI - Whistle-blowers urged to pipe down. PMID- 1504699 TI - A tale of two children. PMID- 1504700 TI - Amniotic fluid embolism and PGs. PMID- 1504701 TI - Serology and AIDS-associated toxoplasmosis. PMID- 1504702 TI - Serology and AIDS-associated toxoplasmosis. PMID- 1504703 TI - Goodbye D&C, welcome hysteroscopy. PMID- 1504704 TI - Why is HIV so malevolently successful? PMID- 1504705 TI - Children's psychiatric services: crisis or media hype? PMID- 1504706 TI - Travellers' diarrhoea. AB - Travellers' diarrhoea affects 15-20 million people each year worldwide. Intestinal infection is the major cause and this can be partially prevented by avoidance of contaminated food and drink. Antimicrobial chemotherapeutic agents are also effective in preventing and treating the condition but widespread indiscriminant use is not recommended. PMID- 1504707 TI - A clinical approach to poorly controlled seizures in children. AB - Uncontrolled seizures are a serious problem and a source of much anxiety to physicians, parents and others concerned with the care of children with epilepsy. A systematic approach to the causes of poor seizure control, considering basic diagnostic, pharmacological, neurological and psychological factors, can reveal treatment possibilities previously unrecognized. PMID- 1504708 TI - Bone scanning. AB - This article outlines the physical and biological bases of bone scanning and then describes the essential features of the technique. The principles underlying the clinical applications are listed, followed by a brief introduction to interpretation of the scan images. PMID- 1504709 TI - Changes in adenosine sensitivity in the hippocampus of rats with streptozotocin induced diabetes. AB - 1. Hippocampal slices have been used to assess the sensitivity of the CNS to adenosine and gamma-aminobutyric acid (GABA) in diabetes. The effects of adenosine, 2-chloroadenosine, GABA, muscimol and baclofen were studied on orthodromic synaptic potentials recorded in the CA1 region of slices taken from normal rats or animals made diabetic by the injection of streptozotocin. 2. In diabetic animals the sensitivity to adenosine was increased 4 fold compared with normal rats. The potency of 2-chloroadenosine was unchanged. 3. The nucleoside transport inhibitor, hydroxynitrobenzylthioinosine (HNBTI), increased the potency of adenosine in slices from normal rats but not in slices from diabetic rats. 4. No change was observed in the potency of GABA or muscimol, although a small but significant decrease was detected in the EC50 value for baclofen. 5. Treatment of diabetic animals with insulin restored the potency of adenosine to control levels. 6. It is concluded that the diabetic state is accompanied by substantial changes of adenosine sensitivity due to the loss of nucleoside uptake processes. Secondary neurochemical changes following from this in human diabetic patients may contribute to the reported behavioural changes. PMID- 1504710 TI - Effect of metformin on glucose metabolism in the splanchnic bed. AB - 1. Use of the antihyperglycaemic agent, metformin, is often associated with a small rise in circulating lactate. This study investigates the source of the lactate and examines the effect of metformin on glucose metabolism by the intestine and liver of rats. 2. Changes in plasma glucose and lactate were measured in the inferior vena cava (IVC), hepatic portal vein (HPV), hepatic vein (HV) and aorta (A) after intrajejunal administration of metformin (50 and 250 mg kg-1) without and with glucose (2 g kg-1). 3. Metformin 250 mg kg-1 reduced the hyperglycaemic response to a glucose challenge, associated with a greater reduction of glucose concentrations in the HPV (average decrease of 33% at 60 and 120 min) than at other sites. 4. Both doses of metformin increased lactate concentrations in the glucose-loaded state: the highest concentration (2.5 fold increase) was recorded in the HPV 60 min after administration of 250 mg kg-1 metformin, with a high lactate concentration persisting in the HV at 120 min. Metformin 250 mg kg-1 also increased lactate concentrations in the basal state, with highest concentrations (2 fold increase) in the HPV. 5. Two hours after intrajejunal administration of metformin, 50 mg kg-1, rings of tissue from the small intestine showed an average 22% decrease in glucose oxidation ([14C] glucose conversion to 14CO2) and a 10% increase in lactate production. Since glucose metabolism in the gut is predominantly anaerobic, metformin caused an overall 9.5% increase of intestinal glucose utilization.6. Metformin, 10-6 and I0 mol 1', did not significantly alter glucose oxidation or lactate production by isolated hepatocytes, but a very high concentration of metformin (102 mol 1') increased lactate production by 60%.7. The results support the view that metformin increased intestinal glucose utilization and lactate production by the intestine. Under basal conditions there was net extraction of lactate by the liver but not after an enteral glucose load. PMID- 1504711 TI - Arterial and venous plasma concentrations of adenosine during haemorrhage. AB - A haemorrhage model was used to impose severe metabolic stress in anaesthetized cats by removing blood (15.3 ml min-1) to attain an arterial pressure of ca. 50 mmHg for a 2 h period. Adenosine levels in central venous blood rose by 5 min, reached a peak of about 3.5 times control levels by 15 min and then returned to the basal level (1 microM) by 60 min. However, the adenosine concentration in arterial blood remained unchanged for the entire 2 h period of hypotension. These data demonstrate that haemorrhage results in rapid adenosine release, but the released adenosine is not able to serve a role as a systemic circulating vasodilator even in this severe model. PMID- 1504712 TI - Enteral absorption of octreotide. AB - 1. The somatostatin octapeptide-analogue, octreotide, is absorbed as intact peptide from the gastrointestinal (GI) tract. 2. In situ absorption experiments in rats confirmed our recent intubation studies in human volunteers demonstrating that the peptide has preferential absorption sites in the small intestine. Absorption of octreotide was higher in the jejunum than in the duodenum or the ileum. 3. Experiments with bile-duct cannulated rats demonstrated that the absorption of octreotide decreased in the presence of bile, reflecting a negative influence of biliary components on the absorption of the peptide. 4. Uptake experiments using rat jejunal brush border membranes were performed to analyse the absorption mechanisms. The transport of octreotide into jejunal brush border membranes was significantly higher than the uptake into membrane vesicles isolated from rat ileum. When initial uptake (0-15s) rates into the membrane vesicles were calculated as a function of the peptide concentration, a saturable component could be observed, indicative of transport mechanisms different from simple diffusion. PMID- 1504713 TI - Evidence that epithelium-dependent relaxation of vascular smooth muscle detected by co-axial bioassays is not attributable to hypoxia. AB - 1. The present study was undertaken to examine further the contribution of hypoxia to airway epithelium-dependent relaxation of rat aorta in the co-axial bioassay. 2. Endothelium-denuded rat aorta contracted with phenylephrine (0.05 microM) relaxed in a time-dependent manner (t1/2 = 8.3 +/- 0.4 min, n = 38) when the bathing solution was bubbled with 95% N2 and 5% CO2. In co-axial bioassays, the t1/2 for histamine (100 microM; guinea-pig trachea)- and methacholine (100 microM; rabbit bronchus)- induced relaxation was 1.9 +/- 0.2 min (n = 14) and 1.2 +/- 0.1 min (n = 26), respectively. 3. Hypoxia-induced relaxation was not associated with a rise in intracellular guanosine 3':5'-cyclic monophosphate (cyclic GMP). This contrasts with previous findings of an elevation in cyclic GMP associated with epithelium-dependent relaxation of rat aorta in co-axial bioassays. 4. Hypoxia-induced vascular relaxation was antagonized by the ATP sensitive K+ channel blocker, glibenclamide (100 microM). In contrast, glibenclamide (100 microM) failed to inhibit histamine (100 microM; guinea-pig trachea)- and methacholine (0.1-100 microM; rabbit bronchus)-induced release of epithelium-derived inhibitory factor (EpDIF), in co-axial bioassays. Glibenclamide (100 microM) antagonized BRL 38227 (lemakalin), but not isoprenaline-induced relaxation of phenylephrine-contracted rat aorta. 5. These data strongly suggest that the airway epithelium-dependent relaxant responses observed in co-axial bioassays cannot be attributed to hypoxia. PMID- 1504714 TI - Sodium-dependence and ouabain-sensitivity of the synthesis of dopamine in renal tissues of the rat. AB - 1. The present study has examined the influence of sodium chloride (0-160 mM) and ouabain (100 and 500 microM), an inhibitor of the enzyme Na(+)-K+ ATPase, on the synthesis of dopamine in slices of rat renal cortex loaded with exogenous L dihydroxyphenylalanine (L-DOPA). The deamination of newly-formed dopamine into 3,4-dihydroxyphenylacetic acid (DOPAC) was also examined. The assay of L-DOPA, dopamine and DOPAC in kidney slices was performed by high performance liquid chromatography (h.p.l.c.) with electrochemical detection. 2. The accumulation of newly-formed dopamine and DOPAC in kidney slices loaded with L-DOPA (50 and 100 microM) was found to be dependent on the concentration of NaCl in the medium. A similar picture could be observed for DOPAC. The fractional rate of accumulation (k; mM NaCl-1) was at 50 and 100 microM L-DOPA, respectively, 0.00305 +/- 0.00036 and 0.00328 +/- 0.00029 for dopamine and 0.00672 +/- 0.00072 and 0.00641 +/- 0.00069 for DOPAC. The sodium-dependent formation of dopamine was completely abolished when the experiments were performed in the absence of oxygen. 3. In experiments performed in the presence of 120 mM NaCl, but not in conditions of low sodium (20 mM NaCl in the medium), ouabain (100 and 500 microM) was found to inhibit the accumulation of newly-formed dopamine and DOPAC (14-57% reduction; P less than 0.05); this effect was more marked at 50 and 100 microM L-DOPA. When the experiments were performed in the absence of oxygen the renal production of dopamine and DOPAC became markedly decreased (respectively, 40% and 77% reduction; P<0.05) and ouabain (100 and 500 microM) was no longer able to reduce the accumulation of both newly-formed dopamine and DOPAC.4. The formation of dopamine and its deamination to DOPAC in kidney homogenates closely depended on the concentration of L-DOPA added to the medium; ouabain (100, 500 and 1000 microM) was found to affect neither the formation of dopamine nor its deamination to DOPAC when homogenates were used instead of kidney slices.5. In conclusion, the results presented here show that the formation of dopamine in kidney slices loaded with L-DOPA is sodium-dependent and ouabain-sensitive suggesting the involvement of a co-transport system of sodium and DOPA into the tubular epithelial cell. PMID- 1504715 TI - ATP overflow from the mouse isolated vas deferens. AB - 1. A modified form of the highly specific luciferin-luciferase assay was used to measure the overflow of adenosine 5'-triphosphate (ATP) from the field-stimulated mouse vas deferens in vitro. Precise timing of the stimulation, superfusate collection and assay minimized ATP degradation before assay, offering the opportunity for quantitative studies. 2. Stimulation with between 50 and 200 supramaximal pulses at 5 Hz increased ATP overflow by between 7 and 28 times over basal. 3. ATP overflow increased steadily with increasing numbers of stimuli from 50 to 200 pulses. Increasing the frequency of stimulation initially had no effect, but above 10 Hz there was increased overflow, suggesting an interaction between facilitated release and the rate of degradation by extracellular ATPases. 4. Contractions of the vas induced by exogenous (-)-phenylephrine produced only a small increase in ATP overflow, suggesting that the stimulation induced increase in ATP overflow is mostly pre-junctional in origin, though tetrodotoxin eliminated stimulation-induced overflow only in a proportion of preparations. PMID- 1504716 TI - The effects of acute and repeated nicotine treatment on nucleus accumbens dopamine and locomotor activity. AB - 1. The effects of acute and subchronic nicotine and (+)-amphetamine on the extracellular levels of dopamine and its metabolites, dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) in nucleus accumbens (NAc) have been studied in conscious, freely-moving rats by use of in vivo microdialysis. 2. In rats which had been habituated to the test apparatus for approximately 80 min, the acute subcutaneous (s.c.) administration of nicotine (0.1 or 0.4 mg kg-1) caused a dose-dependent increase (P less than 0.01) in spontaneous activity and evoked significant increases (P less than 0.05) in the extracellular levels of DOPAC and HVA. 3. Measurements made 24 h after the last injection of nicotine showed that pretreatment with the higher doses tested (0.4 mg kg-1) resulted in increased basal levels of dopamine (P less than 0.01) and decreased basal levels of DOPAC (P less than 0.05) in the NAc dialysates. 4. Pretreatment with nicotine (0.1 or 0.4 mg kg-1 daily for 5 days) enhanced the effects of the drug on spontaneous locomotor activity and enhanced the effects of the drug on extracellular levels of dopamine to the extent that the response became significant (P less than 0.05). 5. If a dopamine uptake inhibitor, nomifensine, was added to the Ringer solution used to dialyse the probe, the s.c. administration of both acute and subchronic nicotine (0.4 mg kg-1) resulted in significant increases (P less than 0.05) in the dopamine concentration in the dialysate. Under these conditions, pretreatment with nicotine prior to the test day prolonged (P less than 0.05) the dopamine response to a challenge dose of nicotine.6. Subcutaneous injections of (+)-amphetamine (0.2 or 0.5 mg kg-') evoked dose-dependent increases in both spontaneous activity and the concentration of dopamine in NAc dialysates. These responses were unaffected by 5 days pretreatment with the drug.7. The results of this study support the conclusion that the enhanced locomotor response to nicotine observed in animals pretreated with the drug prior to the test day is associated with potentiation of its effects on dopamine secretion in the NAc. PMID- 1504717 TI - Effects of purines on the longitudinal muscle of the rat colon. AB - 1. Adenosine and adenosine 5'-triphosphate (ATP) have been reported to cause relaxation of the rat colon longitudinal muscle preparation; the purinoceptors mediating this effect were investigated by use of a series of agonists and antagonists. 2. The tissue was precontracted with carbachol (1 microM), and the purines induced reversible relaxations with a potency order of 5'-N ethylcarboxamidoadenosine (NECA) greater than N6-cyclopentyladenosine (CPA) = adenosine 5'-(alpha, beta-methylene) triphosphonate (AMPCPP) greater than adenosine = adenylyl 5'-(beta, gamma-methylene) disphosphonate (AMPPCP) = ATP. The P1-selective antagonist 1,3-dipropyl-8-cyclopentylxanthine (DPCPX) (3 microM) shifted to the right the log concentration-response curves of all these agonists except for AMPCPP, indicating that they all act via P1-purinoceptors. The order of potency of the adenosine analogues and the relatively high concentrations of the antagonist required indicated that these receptors are of the A2 subtype. The P2-selective antagonist suramin (300 microM) inhibited responses to AMPCPP, but not to the other agonists. 3. The dephosphorylation of the nucleotides was studied by high performance liquid chromatography following incubation with the longitudinal muscle preparation for up to 30 min. ATP was rapidly degraded, largely to adenosine, and AMPPCP and AMPCPP were also degraded, although more slowly, to adenosine and adenosine 5'-(alpha, beta-methylene) diphosphonate (AMPCP) respectively. AMPCP, like AMPCPP, caused relaxations by acting on P2 purinoceptors, as it was also inhibited by suramin (300 microM). Incubation of the tissue with adenosine deaminase abolished responses to adenosine, reduced those to ATP and AMPPCP, but had no effect on those to AMPCPP.ATP and AMPPCP therefore appear to be acting on the A2 receptors in this tissue largely via their degradation product adenosine.4. The longitudinal muscle of the rat colon therefore contains both P.- and P2-purinoceptors, which both mediate relaxation. The P,-purinoceptors are of the A2 subtype and the P2-purinoceptors are probably of the P2Y subtype, although the rapid degradation of the nucleotides means that it is difficult to classify them with certainty. PMID- 1504718 TI - Multiple effects of ryanodine on intracellular free Ca2+ in smooth muscle cells from bovine and porcine coronary artery: modulation of sarcoplasmic reticulum function. AB - 1. The effects of ryanodine and caffeine on intracellular free Ca2+ concentration ([Ca2+]i) were studied by use of fura-2 microfluorometry in single smooth muscle cells freshly dispersed from bovine and porcine coronary artery. 2. Bovine and porcine cells demonstrated similar sensitivities to 10 min of exposure to ryanodine in physiological salt solution (PSS), as determined by comparable dose dependent decreases in the subsequent [Ca2+]i transient induced by 5 mM caffeine. 3. Ryanodine (10 microM) caused a significant increase in [Ca2+]i to a plateau level 27 +/- 3% and 38 +/- 4% above baseline [Ca2+]i (baseline [Ca2+]i = [Ca2+]i at 0 min) in porcine and bovine cells, respectively, when bathed in PSS. In bovine cells the time required to reach 1/2 the plateau level was only 3 min versus 6 min for porcine cells. 4. The ryanodine-induced plateau increase in [Ca2+]i was 35 +/- 5% above baseline for bovine cells bathed in 0 Ca PSS (PSS including 10 microM EGTA with no added Ca2+), but only 7 +/- 3% above baseline in porcine cells during 10 min exposure to 10 microM ryanodine. In bovine cells [Ca2+]i showed proportional increases when extracellular Ca2+ was increased from the normal 2 mM Ca2+ PSS to 5 and 10 mM. 5. Cells pretreated with caffeine in 0 Ca PSS, which depleted the caffeine-sensitive sarcoplasmic reticulum Ca2+ store, showed no increase in [Ca2+]i when challenged with 10 microM ryanodine. The ryanodine-associated increase in [Ca2+]i, which was sustained in 0 Ca PSS during the 10 min ryanodine exposure in cells not pretreated with caffeine, suggests that ryanodine releases Ca2+ from the sarcoplasmic reticulum, but also inhibits Ca2+ efflux.6. Intracellular free Ba2+ ([Ba24],) was measured with fura-2 microfluorometry to define further the Ca2" efflux pathway inhibited by ryanodine; specifically, Ba2+ is not transported by the Ca2" pump, but will substitute for Ca2" in Na+-Ca24 exchange. In porcine cells pretreated with caffeine in 0 Ca PSS to deplete the caffeine-sensitive sarcoplasmic reticulum Ca2+ store, depolarization with 80 mM K4 in 2 mM external Ba24 caused a 100 +/- 6% increase in fura-2 fluorescence ([Ba2+]j). During the 17.5 min 0 Ca PSS recovery from depolarization, exposure to 10 microM ryanodine inhibited the removal of [Ba24]i by 69 + 3% when compared with control (0 Ca PSS without ryanodine).7. It was concluded that in bovine and porcine smooth muscle cells: (a) ryanodine (> 10 microM) releases Ca24 from the sarcoplasmic reticulum; (b) ryanodine ( 10O microM) decreases Ca24 efflux, probably by inhibition of Na+-Ca2+ exchange; (c) the sarcoplasmic reticulum Ca24 store may be larger in bovine than in porcine smooth muscle cells; thus, porcine cells have a relatively greater reliance on Ca24 influx to increase [Ca2+]i. PMID- 1504719 TI - Phosphoramidon potentiates the contractile response to endothelin-3, but not endothelin-1 in isolated airway tissue. AB - 1. Phosphoramidon (10 microM) markedly increased the contractile response to endothelin-3 in human and rabbit bronchus in vitro. In human tissue the contractile response to 0.3 microM endothelin-3 was significantly increased from 54 +/- 12% to 137 +/- 34% (of the response to 1 nM acetylcholine) in the presence of phosphoramidon. Similarly, in rabbit isolated bronchus, the endothelin-3 induced response was increased from 34 +/- 5% to 61 +/- 7%. 2. In addition, the potency (as measured by EC30 values) of this peptide in human and rabbit airways was significantly augmented in the presence of the enzyme inhibitor. The geometric mean EC30 value was decreased from 53 nM (95% CI:15, 190) to 8 nM (95% CI:3, 23) in human bronchus and from 150 nM (95% CI:89, 250) to 23 nM (95% CI:11, 50) in rabbit tissue. 3. Neither the potency nor the response (at 0.3 microM) to endothelin-3 in canine bronchial rings was altered after incubation of the tissue in phosphoramidon. 4. A previous study carried out in human airways has implied that the difference in potency between endothelin-1 and endothelin-3 may be attributed to a heterogeneous endothelin receptor population. The results of our study, while also demonstrating this difference in potency, have shown that this marked difference, as well as that obvious in rabbit airway tissue can be abolished in the presence of phosphoramidon. 5. Phosphoramidon produced no change in the cumulative concentration-response curve for endothelin-1 in airway tissue from the three species studied. 6. These results suggest that a phosphoramidon sensitive enzyme (probably neutral endopeptidase) found in lung, may be responsible for local degradation of endothelin-3, but not endothelin-l in human and rabbit isolated bronchus. PMID- 1504720 TI - Effects of BRL 38227 on neurally-mediated responses in the guinea-pig isolated bronchus. AB - 1. In guinea-pig isolated bronchus treated with indomethacin (2.8 microM), electrical field stimulation (EFS; 10 Hz, 0.5 ms, 60-70 V, for 10 s) evoked a tetrodotoxin (3 microM)-sensitive, biphasic contraction comprising a rapid, atropine (1 microM)-sensitive cholinergic response succeeded by a slowly developing, capsaicin (10 microM)-sensitive, non-adrenergic, non-cholinergic excitatory (NANCe) response. 2. BRL 38227 (0.3-3 microM), salmeterol (0.003-3 microM) and ketotifen (1.0-300 microM) each produced concentration-dependent inhibition of both NANCe and cholinergic responses to EFS in guinea-pig isolated bronchus. 3. Substance P (SP; 1 microM) and neurokinin A (NKA; 0.07 microM) produced contractions equivalent in magnitude to the NANCe response to EFS, which were inhibited by salmeterol (1 microM), but not by BRL 38227 (3 microM) or ketotifen (100 microM). 4. Acetylcholine (ACh; 6 microM) was equi-effective with the electrical activation of cholinergic neurones. BRL 38227 (3 microM) slightly inhibited responses to ACh (6 microM). Salmeterol (1 microM) and ketotifen (100 microM) markedly inhibited responses to ACh (6 microM). 5. In bronchial rings pre contracted with ACh (100 microM), BRL 38227 (0.1-30 microM), salmeterol (0.001-3 microM) and ketotifen (0.1-100 microM) each produced concentration-dependent relaxation. Unlike ketotifen, BRL 38227 and salmeterol only partially (18.8 +/- 2.1% and 51.8 +/- 3.9% respectively) reversed the ACh-induced contraction. 6. The (+)-analogue of BRL 38227, BRL 38226 (0.3-100 microM), was without effect on responses to EFS and had no effect on the inhibition caused by BRL 38227. The K+ channel activators pinacidil (3.0-30 microM) and RP 52891 (3.0-30 microM) exerted similar inhibitory actions on responses to EFS as BRL 38227, but were less potent. Glibenclamide (0.1-1.O microM) and phentolamine (3 microM) antagonized the inhibitory effects of BRL 38227 on responses to EFS.7. It is concluded that BRL 38227 and ketotifen can inhibit NANCe neuroeffector transmission at concentrations exerting little or no inhibitory effects on responses to exogenously applied tachykinins.By contrast, in addition to suppressing NANCe responses to EFS, salmeterol also markedly inhibits responses to SP and NKA. At concentrations markedly suppressing cholinergic neuroeffector transmission, BRL 38227 has only minor effects on responses to exogenously-applied ACh. Salmeterol and ketotifen both depress responses to ACh within the concentration-range over which they inhibit cholinergic responses to EFS. The inhibitory effects of BRL 38227 on responses to EFS exhibit stereo-specificity and may involve the opening of a neuronal K+-channel. This K+-channel is glibenclamide-and phentolamine sensitive and appears similar to the smooth muscle K+-channel which is modulated by BRL 38227. PMID- 1504721 TI - Synergism between the contractile effect of epidermal growth factor and that of des-Arg9-bradykinin or of alpha-thrombin in rabbit aortic rings. AB - 1. Rabbit aortic rings were used to test the possible contractile effects of growth factors and their interaction with other stimuli. A rapid potentiation of kinin-induced contraction by epidermal growth factor (EGF) has been previously observed in this preparation. 2. EGF (5-1500 ng ml-1) and the isoform BB of platelet-derived growth factor (PDGF-BB; 1-126 ng ml-1) exerted modest but sustained contractile effects in rabbit aortic rings. 3. EGF pretreatment (100 ng ml-1) potentiated the contractile responses to des-Arg9-bradykinin (des-Arg9-BK), an agonist of the B1 receptors for kinin found in this preparation, and to human alpha-thrombin but not to several other contractile stimuli. The interaction appeared also relatively selective for the growth factor, because PDGF-BB pretreatment potentiated neither des-Arg9-BK nor alpha-thrombin-induced contraction. 4. EGF, applied on a contraction plateau induced by des-Arg9-BK or alpha-thrombin, exerted a synergistic contractile effect, with a time course and a half-maximal concentration for EGF-induced contraction similar to the ones recorded in resting tissues (between 67 and 220 ng ml-1, depending on the series of experiments). 5. The direct or synergistic contractile effects of EGF were not modified by the removal of the endothelium or by treatment with indomethacin. However, the tyrosine kinase inhibitors, erbstatin or genistein, inhibited the synergistic effect of EGF with des-Arg9-BK. The small direct contractile effect of EGF was significantly reduced by genistein. The synergistic effect of EGF with alpha-thrombin was comparatively more resistant to the tested tyrosine kinase inhibitors.6. An inhibitor of the catalytic activity of alpha-thrombin, D-Phe-Pro Arg-CH2Cl, prevented the contractile effect of x-thrombin in the aortic rings. In this system, a tetradecapeptide derived from a recently cloned alpha-thrombin receptor was a contractile stimulus at and above 10 microM. Consistent with the hypothesis that this peptide could behave as an alpha-thrombin receptor agonist, its contractile effect was potentiated by EGF pretreatment. Pharmacological evidence was provided to show that the receptors for alpha-thrombin were distinct from the B, receptors for kinins. Together, these findings suggest that a model of a cleavable receptor recently elaborated to account for alpha-thrombin effects on human platelets is valid in blood-free vascular smooth muscle preparations such as the rabbit isolated aorta.7. The synergism between EGF and kinin- or alpha-thrombin-induced contractions constitutes a novel mode of myotropic action for growth factors. The synergism is probably dependent on the tyrosine kinase activity of receptors for EGF. These combinations of stimuli could occur in various types of vascular disease and account for abnormal vascular reactivity often associated with atheroma lesions or vascular wound healing. PMID- 1504722 TI - The pharmacological modulation of thrombin-induced cerebral thromboembolism in the rabbit. AB - 1. Intracarotid (i.c.) administration of thrombin induced a marked accumulation of 111indium-labelled platelets and 125I-labelled fibrinogen within the cranial vasculature of anaesthetized rabbits. 2. Thrombin (100 iu kg-1, i.c.) - induced platelet accumulation was completely abolished by pretreatment with desulphatohirudin (CGP 39393; 1 mg kg-1 i.c., 1 min prior to thrombin). Administration of CGP 39393 1 or 20 min after thrombin produced a significant reduction in platelet accumulation. 3. Intravenous (i.v.) administration of the platelet activating factor (PAF) receptor antagonist BN 52021 (10 mg kg-1) 5 min prior to thrombin (100 iu kg-1, i.c.) had no effect on platelet accumulation. 4. An inhibitor of NO biosynthesis, L-NG-nitro arginine methyl ester (L-NAME; 100 mg kg-1, i.c.), had no significant effect on the cranial platelet accumulation response to thrombin (10 iu kg-1, i.c.) when administered 5 min prior to thrombin. 5. Defibrotide (32 or 64 mg kg-1 bolus i.c. followed by 32 or 64 mg kg 1 h-1, i.c., infusion for 45 min) treatment begun 20 min after thrombin (100 iu kg-1, i.c.) did not significantly modify the cranial platelet accumulation response. 6. Cranial platelet accumulation induced by thrombin (100 iu kg-1, i.c.) was significantly reversed by the fibrinolytic drugs urokinase (20 iu kg-1, i.c., infusion for 45 min), anisoylated plasminogen streptokinase activator complex (APSAC) (200 micrograms kg-1, i.v. bolus) or recombinant tissue plasminogen activator (rt-PA; 100 micrograms kg-1, i.c. bolus followed by 20 micrograms kg-1 min-1, i.c., infusion for 45 min) administered 20 min after thrombin.8. These results suggest that neither endogenous PAF nor NO modulate thrombin-induced intracranial platelet accumulation in the rabbit. However, fibrin deposition appears to play an important role as shown by the ability of fibrinolytic agents to reverse platelet and fibrinogen accumulation induced by i.c. thrombin. PMID- 1504723 TI - Opposing roles for 5-HT1B and 5-HT3 receptors in the control of 5-HT release in rat hippocampus in vivo. AB - 1. Intracerebral microdialysis was used to determine whether 5-hydroxytryptamine (5-HT) release in the ventral hippocampus of rats anaesthetized with chloral hydrate was modulated by 5-HT3 receptors. 2. It was confirmed that 5-methoxy-3 (1,2,3,6-tetrahydro-4-pyridinyl)-1H-indole (RU 24969), a selective 5-HT1B receptor agonist, decreased 5-HT release in a dose- and concentration-related manner when administered i.p. (1 and 5 mg kg-1) or via the dialysis probe (0.1 and 1 microM) respectively. The effect of RU 24969 infusion (1 microM) was attenuated by concurrent infusion of metitepine (10 microM) into the hippocampus. 3. When infused into the hippocampus for 15 min, the selective 5-HT3 receptor agonist, 2-methyl-5-hydroxytryptamine (2-methyl-5-HT; 0.1- 10 microM) increased dialysate 5-HT levels in a concentration-related manner; an effect which was abolished by concurrent infusion of 3-tropanyl-3,5-dichlorobenzoate (1 microM, MDL 72222), a selective 5-HT3 antagonist. 4. MDL 72222 had no effects on hippocampal 5-HT release when administered via the dialysis probe (1 or 10 microM). 5. The data show that 5-HT3 and 5-HT1B receptors have opposing roles in the control of 5-HT release in the hippocampus, with 5-HT3 receptors facilitating and 5-HT1B receptors inhibiting 5-HT efflux, respectively. They also indicate that the facilitatory 5-HT3 receptors are not tonically activated. PMID- 1504724 TI - Contractions induced by potassium-free solution and potassium relaxation in vascular smooth muscle of hypertensive and normotensive rats. AB - 1. Vascular contractions induced by K(+)-free solution and relaxation responses following the return of K+ to the organ bath were studied in mesenteric arterial rings from spontaneously hypertensive rats (SHR) and normotensive Wistar-Kyoto rats (WKY) with particular focus on the role of vascular adrenergic nerve-endings and endothelium. 2. In endothelium-denuded rings the omission of K+ from the incubation medium resulted in gradual contractions, the rate of which was slower in SHR than WKY. Nifedipine (1 microM) inhibited the contractions more effectively in SHR than WKY. 3. Adrenergic denervation in vitro with 6 hydroxydopamine reduced the contractions induced by the K(+)-free medium in endothelium-denuded rings. The remaining contractions after denervation were markedly greater in SHR than WKY. 4. The presence of intact vascular endothelium attenuated the K(+)-free contractions in both strains, the attenuation being smaller in SHR than WKY. NG-nitro-L-arginine methyl ester (L-NAME, 0.1 mM) and methylene blue (10 microM), but not indomethacin (10 microM), abolished the attenuating effect of endothelium on the K(+)-free contractions. L-Arginine (1 mM) reversed the effect of L-NAME in WKY but not in SHR. 5. The re-addition of K+ after full K(+)-free contractions dose-dependently relaxed the rings. The rate of this K(+)-induced relaxation was significantly slower in SHR than WKY at all K+ concentrations (0.1-5.9 mM) studied, whether the endothelium or functioning adrenergic nerve-endings were present or not. Ouabain (1 mM) totally inhibited the K+ relaxation in SHR but only partially in WKY.6. Vascular smooth muscle contractions induced by high concentrations of potassium were comparable between the strains. The EC50 for noradrenaline-induced contractions was lower in SHR than WKY, but the maximal forces did not differ significantly.7. In conclusion, the contractile response in K+-free solution more clearly differentiates vascular rings from SHR and WKY than the responses induced by the classical contractile agents noradrenaline and high concentrations of potassium. The depressant effect of the presence of intact endothelium on the K+-free contractions, which was smaller in SHR than WKY, is mediated via the endothelium-derived relaxing factor. Neurotransmitter release from vascular adrenergic nerve-endings participates less in the K+-free contractile response in SHR than WKY. Moreover, the contractile response is more dependent on calcium entry through nifedipine-sensitive calcium channels in SHR than WKY. The greater K+-free contractions of denervated endothelium-denuded rings and the reduced K+ relaxation rate in SHR when compared to WKY suggest increased cell membrane permeability and decreased activity of vascular Na+, K+-ATPase, respectively, in this type of genetic hypertension. PMID- 1504725 TI - The involvement of potassium channels in the action of ciclazindol in rat portal vein. AB - 1. In whole portal veins, ciclazindol (0.3-10 microM) increased the amplitude and duration, but decreased the frequency of spontaneous contractions. Glibenclamide (0.3-10 microM) produced a small increase in contraction amplitude and duration with a small reduction in contraction frequency. 2. In whole portal veins, ciclazindol (1-10 microM) antagonized the relaxant effects of BRL 38227 in a non competitive manner. Under identical conditions, the effects of glibenclamide (0.3 10 microM) appeared to be competitive. 3. In whole portal veins loaded with 42K, ciclazindol itself (up to 3 microM) had no detectable effect on basal 42K exchange. However, the increase in 42K efflux produced by BRL 38227 (5 microM) was antagonized by ciclazindol (3 microM). Similar effects were produced by glibenclamide (up to 3 microM). 4. In freshly-isolated portal vein cells examined by the whole-cell voltage-clamp technique, ciclazindol (1-100 microM) inhibited the slowly-activating and inactivating transient outward current (ITO) which could be generated at potentials more positive than -30 mV. In addition ciclazindol (1-10 microM) inhibited the non-inactivating K-current (IKCO) induced by BRL 38227 (10 microM). 5. In freshly-isolated portal vein cells under current clamp conditions, the hyperpolarization produced by BRL 38227 (10 microM) was reversed by ciclazindol (1-10 microM). 6. In porcine brain membrane fragments, glibenclamide (0.65 nM) displaced 50% of the binding of [3H]-glibenclamide whereas ciclazindol (up to 10 microM) had no effect. 7. It is concluded that ciclazindol is a K-channel blocker. Its action is not selective for the channel(s) which carry IKCO but also extends to those which carry ITO.Its inability to displace [3H]-glibenclamide from porcine brain fragments may indicate that antagonism of BRL 38227 by ciclazindol in smooth muscle is exerted at a site different from that of glibenclamide. PMID- 1504726 TI - Influence of NG-nitro-L-arginine on non-adrenergic non-cholinergic relaxation in the guinea-pig gastric fundus. AB - 1. The influence of NG-nitro-L-Arginine (L-NNA) on non-adrenergic non-cholinergic (NANC) relaxations induced by electrical field stimulation was investigated in circular muscle strips of the guinea-pig gastric fundus. 2. In the presence of 10(-6) M atropine and 4 x 10(-6) M guanethidine, electrical field stimulation (40 V, 1 ms, 0.125-16 Hz) with 10 s trains at 5 min intervals induced short-lasting, frequency-dependent relaxations. Continuous stimulation, with cumulative increase of the stimulation frequency, induced sustained frequency-dependent relaxations. Both types of response were abolished by 3 x 10(-6) M tetrodotoxin. 3. L-NNA (10( 5) M and 10(-4) M) concentration-dependently reduced both types of NANC response. Pre-incubation with 2 x 10(-3) M L-arginine prevented the inhibitory action of 10(-5) M L-NNA and partially antagonized that of 10(-4) M L-NNA. D-arginine (2 x 10(-3) M) did not protect against the inhibitory effect of L-NNA. 4. L-NNA did not consistently influence the basal tone of the tissues. L-Arginine and D arginine likewise did not influence basal tone; they also had no influence on the electrically-induced NANC relaxations. 5. NO (10(-6)-10(-4) M) induced short lasting concentration-dependent relaxations, while vasoactive intestinal polypeptide (VIP, (10(-9)-10(-7) M) induced more sustained relaxations, that developed at a slower rate. The NO- and VIP-induced relaxations were not influenced by 10(-4) M L-NNA.6. These results suggest that NO is involved in NANC neurotransmission of the guinea-pig gastric fundus; its contribution to sustained NANC relaxation in the guinea-pig gastric fundus is much more important than in the rat. PMID- 1504727 TI - Haemodynamic and abdominal motor reflexes elicited by neurotensin in anaesthetized guinea-pigs. AB - 1. Single intraperitoneal (i.p.) injections of neurotensin (NT) (0.14- 140 nmol kg-1) in anaesthetized guinea-pigs were found to trigger transient abdominal wall contractions (TAWC) accompanied by relatively sustained increases of systemic blood pressure (BP) and heart rate (HR). The modification of the latter NT effects by various drugs and surgical manipulations was examined to obtain some insight into the nature of, and possible relationship between, these responses. 2. The abdominal motor response (i.e. TAWC) to i.p. NT (14 nmol kg-1) was inhibited by prior i.v. injection of the guinea-pigs with pancuronium (0.27 mumol kg-1), morphine (1.5 and 15 mumol kg-1), clonidine (0.34 mumol kg-1), by concomitant i.p. injection of procaine 2% w/v, or by acute spinalization. It was potentiated by naloxone (2.8 and 28 mumol kg-1), but not affected by i.v. injection of autonomic drugs (i.e. pentolinium, prazosin, yohimbine and atropine), by capsaicin desensitization, or by acute bilateral cervical vagotomy. In spinalized animals a sustained abdominal wall contraction (SAWC) was unmasked, which was resistant to i.v. morphine, clonidine or baclofen but suppressed by i.v. pancuronium or i.p. lignocaine 2% w/v. 3. Haemodynamic responses to i.p. NT were not affected by i.v. pancuronium, morphine, naloxone, atropine, or by vagotomy. They were inhibited by i.v. pentolinium or clonidine (BP, HR), i.v. prazosin (BP), i.p. procaine 2% w/v (BP, HR), capsaicin desensitization or acute spinalization (BP, HR). Yohimbine (i.v.) potentiated BP and HR increases caused by i.p. NT.4. These results suggest that: (1) the haemodynamic and TAWC responses to i.p. NT in this animal model, are two independent, neurally-mediated reflexes which are likely to originate from the abdominal cavity and require a functionally intact spinal cord for their full expression; (2) the neural pathways subserving both types of responses appear to be different from each other. The nature and time-response characteristics of the reflexes caused by i.p. NT, raise the possibility that i.p. NT is a noxious stimulus, at least in guinea-pigs. PMID- 1504728 TI - Effects of a new pteridine derivative on urinary sodium, potassium and magnesium excretion in conscious saline-loaded rats. AB - 1. Two recently synthesized pteridine derivatives (RPH 3036; RPH 3038) were tested in conscious saline-loaded rats and showed natriuretic and antimagnesiuretic properties but hardly reduced potassium excretion. 2. In the same model a dose-response curve was performed for RPH 3036. ED50 and Emax values were calculated for the natriuretic (ED50 = 13.4 mumol kg-1; Emax = 1.08 mmol kg 1) and antimagnesiuretic (ED50 = 11.3 mumol kg-1; Emax = -0.099 mmol kg-1) properties of RPH 3036. There were no significant changes of potassium and calcium excretion. 3. After a single dose of RPH 3036 (100 mumol kg-1) the time course of electrolyte excretion was analysed over 6 h. RPH 3036 did not show any significant effects on renal potassium and calcium excretion whereas a pronounced decrease (P less than 0.01) in renal magnesium excretion was evident during the 6 h. A moderate increase of sodium excretion was observed only after 3, 5 and 6 h. 4. A selective reduction of magnesium secretion in the late distal tubule and collecting duct was proposed as a possible mechanism of action of RPH 3036. This would explain the fast onset of action as well as the lack of antikaliuretic and anticalciuretic effects. The high selectivity of RPH 3036 makes it potentially valuable for the future investigation of renal magnesium transport. PMID- 1504729 TI - Modulation by peripheral opioids of basal and distension-stimulated gastric acid secretion in the rat. AB - 1. The influence of opioids in modulating gastric acid secretory responses has been investigated in the continuously perfused stomach of the anaesthetized rat. 2. Intravenous administration of morphine (0.75-3 mg kg-1) or the peripherally acting enkephalin analogue, BW443C (0.75-3 mg kg-1), substantially augmented acid secretion in basal conditions. These effects were significantly inhibited by the opioid antagonists naloxone (1 mg kg-1) and the peripherally acting N methylnalorphine (2 mg kg-1). When administered alone, neither opioid antagonist influenced basal acid output. 3. Acid secretory responses to different levels of gastric distension (5-20 cmH2O) were significantly and dose-dependently reduced in rats pretreated with morphine (3 mg kg-1) or BW443C (1.5 mg kg-1). Previous administration of either naloxone or N-methyl nalorphine reversed the inhibitory effects of opioids on gastric acid secretion stimulated by distension. Likewise, blockade of opioid receptors with naloxone or N-methylnalorphine significantly increased acid output induced by distension. 4. Levels of serum gastrin in control animals were not increased after intragastric distension (20 cmH2O). Pretreatment with BW443C (1.5 mg kg-1) did not modify the levels of gastrin present during basal or distension stimulated conditions. 5. Pretreatment with morphine or BW443C did not influence the acid responses to i.v. injection of pentagastrin (100 micrograms kg-1), histamine (5 mg kg-1) or carbachol (4 micrograms kg-1). Acid secretion induced by i.v. administration of 2-deoxy-D glucose (150 mg kg-1) was reduced in rats pretreated with morphine but not with BW443C. Gastric secretory responses to insulin (0.3 i.u. kg-1) were not modified by i.v. morphine.6. These observations support a role for peripherally acting opioids in the regulation of gastric acid secretion during basal and distension stimulated conditions. PMID- 1504730 TI - Mechanism of the vasodilator action of calcitonin gene-related peptide in conscious rats. AB - 1. The aim of this study was to investigate whether the hypotensive effect of rat alpha-calcitonin gene-related peptide (alpha CGRP) in conscious rats is mediated by endothelium-derived nitric oxide (NO) or the opening of adenosine 5' triphosphate (ATP)-sensitive potassium (KATP) channels. 2. Dose-mean arterial pressure (MAP)-response curves of alpha CGRP were examined in the presence of vehicle, phenylephrine, KATP channel antagonist glibenclamide or NO synthase inhibitors, NG-nitro-L-arginine methyl ester (L-NAME) and NG-nitro-D-arginine methyl ester (D-NAME). Dose-MAP-response curves for sodium nitroprusside were also constructed in the presence and absence of L-NAME and D-NAME. 3. alpha CGRP and nitroprusside produced dose-dependent reductions in MAP which were potentiated by phenylephrine. Both L-NAME and D-NAME attenuated the depressor response to alpha CGRP but not nitroprusside. 4. Dose-MAP-response curves for pinacidil, a KATP-channel activator, were also examined in the presence of glibenclamide or vehicle. Glibenclamide attenuated pinacidil- but not alpha CGRP induced reductions in MAP. 5. It is concluded that the hypotensive effects of alpha CGRP are partially mediated via endothelium-derived NO but not via the opening of KATP channels. PMID- 1504731 TI - Studies on curare-like action of 2,2',2''-tripyridine in the mouse phrenic nerve diaphragm. AB - 1. The curare-like action of 2,2',2''-tripyridine (a synthetic by-product of the herbicide, paraquat) was studied in mouse phrenic nerve-diaphragm preparation. The inhibition by 2,2',2''-tripyridine of nerve-evoked twitches was dependent on the concentration, ranging from 1 to 100 microM, which had no significant effect on the twitch amplitudes evoked by direct muscle stimulation. 2. The twitch inhibition by 2,2',2''-tripyridine was reversible and could be antagonized by anticholinesterase agents such as neostigmine, physostigmine as well as ecothiophate. 3. Pretreatment with either 0.7 microM (+)-tubocurarine or 2.2 microM succinylcholine shifted the concentration-inhibition curve of 2,2',2'' tripyridine to the left. 4. 2,2'2''-Tripyridine inhibited not only acetylcholine induced contracture of the denervated mouse diaphragm but also that of the chick biventer cervicis muscle. Like (+)-tubocurarine, 2,2',2''-tripyridine protected the twitches from the inhibition by alpha-bungarotoxin and also specifically inhibited the binding of [125I]-alpha-bungarotoxin to the mouse diaphragm. All of these findings indicate that 2,2',2''-tripyridine possesses curare-like action and inhibits the muscle contractions through binding to postsynaptic acetylcholine receptors. 5. The postsynaptic inhibition exhibited by 2,2',2'' tripyridine was also implicated in the tetanic fade, a decrease in the amplitude of miniature endplate potential (m.e.p.p.) and endplate potential (e.p.p.). 6. The clinical implication of these findings is that 2,2',2''-tripyridine may be involved in the cause of respiratory failure in paraquat-intoxicated workers since 2,2',2''-tripyridine is a by-product of paraquat synthesis. PMID- 1504732 TI - Combined dose-ratio analysis of cholecystokinin receptor antagonists, devazepide, lorglumide and loxiglumide in the guinea-pig gall bladder. AB - 1. Interactions between cholecystokinin octapeptide (CCK-8) and CCKA-receptor antagonists derived from benzodiazepines (devazepide) and glutamic acid (lorglumide and loxiglumide) have been examined in an improved bioassay using the guinea-pig, isolated, gall bladder preparation. 2. The presence of CCKB-receptors in the assay was provisionally-ruled out on the basis of the low potency of pentagastrin in the assay. By applying analyses of both agonism and antagonism, pentagastrin was shown to behave as a partial agonist at the CCKA-receptor. 3. Devazepide, lorglumide and loxiglumide behaved as simple competitive antagonists of CCKA-receptors and pKB values of 9.98, 7.59 and 7.07 were estimated, respectively. 4. Application of a combined dose-ratio analysis to the interactions between CCK-8 and combinations of devazepide/lorglumide and devazepide/loxiglumide indicated that these molecules behave as syntopic, competitive, antagonists at the CCKA-receptor. 5. We conclude that the guinea-pig gall bladder assay contains a homogeneous population of CCKA-receptors and offer an explanation for the differences between our results and those obtained recently by Maubach et al. (1991) which were taken as preliminary evidence for CCKA-receptor heterogeneity. PMID- 1504733 TI - Intervascular and stimulus selectivity of nitrendipine and related derivatives in KCl and prostaglandin F2 alpha precontracted porcine arteries. AB - 1. Dihydropyridine-type calcium entry blockers exhibit a different vasodilator potency depending on the arterial tissue (intervascular selectivity) as well as on the precontracting stimulus used (stimulus selectivity). In addition, the structure of their ester side chains seems to influence their activity. 2. Vascular activity of nitrendipine and six related 3-ester side chain derivatives was investigated in isolated coronary, ulnar and basilar arteries of the pig following precontraction with KCl or prostaglandin F2 alpha (PGF2 alpha). 3. After depolarization, all dihydropyridines exhibited a weak preferential action on coronary arteries. Bay E 6927 produced the strongest effect in all vessel types. By contrast, precontraction with PGF2 alpha resulted in a marked preferential action in basilar arteries, although higher concentrations of the dihydropyridines were required for half maximal vasorelaxation. In each case, ulnar arteries were less sensitive. 4. Except with Bay O 5572, the most bulky substituted and least active derivative, only moderate differences were observed within the dihydropyridines studied. On the other hand, there was a pronounced increase in the ratios of the half maximal active concentrations required after precontraction of the vessels with PGF2 alpha compared to KCl (stimulus selectivity) following a limited prolongation of the 3-ester side chain up to an isopropyl-group. 5. It is suggested that the observed shift in the intervascular selectivity after precontraction with PGF2 alpha is a consequence of different contractile mechanisms in the three vessel types studied. The degree of the stimulus selectivity may also depend on the structure of the dihydropyridines. PMID- 1504734 TI - Comparison of the actions of acetylcholine and BRL 38227 in the guinea-pig coronary artery. AB - 1. The contractile and electrical responses to acetylcholine (ACh) in isolated segments of guinea-pig and rabbit coronary arteries were compared to those of the putative adenosine 5'-triphosphate (ATP)-dependent K+ channel opener, BRL 38227. 2. Both ACh and BRL 38227 produced concentration-dependent relaxation of vessel segments contracted with the H1-receptor agonist, 2-(2-aminoethyl)pyridine. 3. An IC90 of either vasodilator also produced 17-20 mV of hyperpolarization of the guinea-pig coronary artery. 4. Glibenclamide (1-35 microM) depolarized the guinea pig coronary artery by 8-12 mV and antagonized BRL 38227- but not ACh-induced relaxation and hyperpolarization. 5. In the guinea-pig coronary artery, the K+ channel blockers phencyclidine (PCP, 100 microM), tetraethylammonium (TEA, 10 mM) and scorpion venom (8.7 micrograms ml-1) all significantly reduced ACh-induced relaxation and hyperpolarization whereas only PCP was an effective antagonist of both relaxation and hyperpolarization with BRL 38227. 6. Similar effects of glibenclamide and scorpion venom on ACh- and BRL 38227-induced relaxation were observed in the rabbit coronary artery. 7. Apamin (3.5 microM) was without effect on either the ACh- or BRL 38227-induced relaxation in the guinea-pig coronary artery. 8. In conclusion, the actions of BRL 38227 in coronary artery are compatible with its proposed effects on ATP-dependent K+ channels. In contrast, the results with ACh suggest that some step between the initial binding of ACh to endothelial muscarinic receptors and the final relaxation of the smooth muscle depends upon the opening of Ca(2+)-activated K+ channels. PMID- 1504735 TI - Human brain contains a metalloprotease that converts big endothelin-1 to endothelin-1 and is inhibited by phosphoramidon and EDTA. AB - Incubation of big endothelin-1 (bET-1) with protein derived from the detergent extracted 100,000 g pellet prepared from human brain tissue resulted in the formation of endothelin-1 (ET-1) at a rate of 90 fmol mg-1 protein min-1. This formation was inhibited in a concentration-dependent manner by either phosphoramidon or EDTA, with half-maximal inhibitory concentrations of 2 and 20 microM, respectively. No conversion of big endothelin-3 (bET-3) to endothelin-3 (ET-3) was detected under the same conditions. These results show the presence in the human brain of a metalloprotease-like enzymatic activity which selectively converts bET-1 and ET-1. Together with earlier reports of mRNA for ET-1 this suggests the presence of the entire synthetic pathway for ET-1 in human brain. PMID- 1504736 TI - Dependence of the metabolism of nitric oxide (NO) in healthy human whole blood on the oxygenation of its red cell haemoglobin. AB - Plasma or whole venous or arterialized blood from healthy human donors was incubated with NO (50-300 microM), and the resulting formation of methaemoglobin (MetHb), nitrosyl haemoglobin (HbNO), and plasma nitrite and nitrate were measured. In plasma, NO was converted to nitrite and nitrate in a ratio of 5:1. In arterial blood (O2 sat. 94-99%) NO was almost quantitatively converted to nitrate and MetHb. No nitrite was detected and HbNO formation was low. In venous blood (O2 sat. 36-85%) more HbNO and less nitrate was formed, in comparison to arterialized blood. We propose that NO liberated from endothelium of conductance and resistance vessels is taken up by red blood cells and inactivated by HbO2 via stoichiometric conversion to MetHb and nitrate. PMID- 1504737 TI - Ionic mechanisms responsible for the antiarrhythmic action of dehydroevodiamine in guinea-pig isolated cardiomyocytes. AB - 1. Dehydroevodiamine alkaloid (DeHE), an active ingredient of a Chinese herbal medicine Wu-Chu-Yu (Evodiae frutus), has been shown to decrease aterial blood pressure in experimental animals and prolong action potential duration in cardiac cells. The aim of the present study was to explore the ionic basis of its possible antiarrhythmic effects. 2. Guinea-pig atrial and ventricular myocytes were isolated enzymatically and the ionic currents were recorded under whole-cell patch-clamp with single suction pipettes. 3. DeHE at a concentration of 0.1 microM inhibited reversibly the time-dependent outward K current (delayed rectifier, Ik) and the Na-dependent inward current (INa). 4. In low-K (1 mM) and high-Ca (9 mM) solution, DeHE also depressed the delayed afterdepolarizations (DAD) and the transient inward current (Iti) induced by 2 microM strophanthidin. On the other hand, DeHE occasionally induced early afterdepolarizations and slow response action potentials at a depolarized level. 5. At higher concentrations (1 microM and above), the L-type Ca current (ICa,L) was moderately inhibited. 6. The present findings indicate that DeHE may depress triggered arrhythmias in Ca overloaded guinea-pig cardiac myocytes through its inhibitory actions on INa, Iti and, to a smaller extent, ICa. DeHE may also exert class III antiarrhythmic effect through a reduction of outward K currents (Ik) across the sarcolemma. PMID- 1504738 TI - Pharmacological characteristics of 5-hydroxytryptamine autoreceptors in rat brain slices incorporating the dorsal raphe or the suprachiasmatic nucleus. AB - 1. Changes in extracellular concentrations of 5-hydroxytryptamine elicited by electrical stimulation in rat brain slices containing the dorsal raphe nucleus and the suprachiasmatic nucleus were monitored with fast cyclic voltammetry. 2. Using pseudo single pulse stimulation (5 pulses applied at 100 Hz) we have shown that the release of 5-hydroxytryptamine in the dorsal raphe and the suprachiasmatic nucleus can be regulated by autoreceptors in both brain regions. 3. In the suprachiasmatic nucleus, 5-carboxamidotryptamine, RU24969, 1-(m trifluoromethylphenyl) piperazine and sumatriptan caused a concentration dependent inhibition of stimulated 5-hydroxytryptamine overflow in the range 1 x 10(-9) M to 3 x 10(-6) M. The actions of 5-carboxamidotryptamine and RU24969 were reversed competitively by methiothepin (10(-8) M to 10(-6) M); Schild plots revealed pKB values of 7.9 and 8.1. By contrast, ipsaparone and 8-hydroxy-2(di-n propylamino)tetralin (8-OH-DPAT) are not effective 5-hydroxytryptamine autoreceptor agonists in the suprachiasmatic nucleus. 4. Isamoltane (10(-6) M), the putative 5-HT1B receptor antagonist, blocked the responses to RU24969 (10(-6) M) and 1-(m-trifluoromethylphenyl)piperazine (10(-6) M) in the suprachiasmatic nucleus. 5. In the dorsal raphe nucleus, 8-OH-DPAT, ipsapirone, RU24969, 5 carboxamidotryptamine, and sumatriptan (all 1 x 10(-8) M to 3 x 10(-6) M) produced a concentration-dependent reduction in the stimulated release of 5 hydroxytryptamine. The maximum effect observed was less than that seen in the suprachiasmatic nucleus.6. Methiothepin (1 10-7 M) blocked the effect of 5 carboxyamidotryptamine (10-8 M to 10-6 M) in the dorsal raphe nucleus while propranolol (10-6 M) and NAN-190 (10-6 M) but not isamoltane (10-6 M) were found to block significantly the effect of ipsapirone (10-6 M).7. We conclude, that drugs with 5-HTIA binding activity act as agonists in the dorsal raphe nucleus while drugs showing some activity for 5-HTIB and 5-HTID binding sites, act as agonists in the suprachiasmatic nucleus. Our results confirm predictions from binding studies, that functional 5-HT autoreceptors regulating release of endogenous 5-HT have different drug specificity in the dorsal raphe and suprachiasmatic nucleus. PMID- 1504739 TI - Receptor-coupled shortening of alpha-toxin-permeabilized single smooth muscle cells from the guinea-pig stomach. AB - 1. Isolated single smooth muscle cells from the fundus of the guinea-pig stomach were permeabilized by use of Staphylococcus aureus alpha-toxin. Receptor-coupled shortening of individual cells was monitored under phase contrast microscopy. 2. Most of the isolated cells responded to 0.6 microM Ca2+, but not to 0.3 microM Ca2+, with a resulting maximal shortening to approximately 65% of the resting cell length. The contractile activity of these permeabilized cells lasted for several hours and repeated shortening was readily achieved after washing out. 3. Addition of acetylcholine (ACh) at a maximal concentration (10 microM) resulted in a marked decrease in the concentration of Ca2+ required to trigger a threshold response from 0.6 microM to 0.2 microM, and 1 mM guanosine 5'-diphosphate (GDP) blocked this decrease. Moreover, treatment with 100 microM guanosine 5' triphosphate (GTP) mimicked the action of ACh. 4. Addition of 100 microM inositol 1,4,5-trisphosphate (InsP3) with 0.2 microM Ca2+ did not cause cell shortening, whereas 10 microM ACh with 0.2 microM Ca2+ did, suggesting that InsP3-induced Ca2+ release is not involved in ACh-operated cell shortening. 5. The present study demonstrates an alpha-toxin-permeabilized single smooth muscle cell preparation which retains its receptor function and also provides an insight into mechanisms leading to augmentation of Ca2+ sensitivity by stimulation of muscarinic receptors or GTP-binding proteins. PMID- 1504741 TI - Phenytoin potentiates interleukin-1-induced prostaglandin biosynthesis in human gingival fibroblasts. AB - 1. The effect of phenytoin (PHT) on prostaglandin E2 (PGE2) biosynthesis in human gingival fibroblasts stimulated by interleukin-1 (IL-1 alpha, IL-1 beta) or by tumour necrosis factor alpha (TNF alpha) was studied. 2. IL-1 alpha (1.5-6.0 ng ml-1) and IL-1 beta (30-300 pg ml-1), dose-dependently, stimulated PGE2 formation, in 24 h cultures, with IL-beta being the most potent agonist. 3. PHT (2.5-20 micrograms ml-1) did not induce PGE2 formation itself but potentiated IL 1 alpha- and IL-1 beta-induced PGE2 formation in the gingival fibroblasts in a manner dependent on the concentrations of both IL-1 and PHT. 4. IL-1 beta (0.1 1.0 ng ml-1) induced release of [3H]-arachidonic acid ([3H]-AA) from prelabelled fibroblasts that was potentiated by PHT (20 micrograms ml-1). 5. TNF-alpha (greater than or equal to 0.01 micrograms ml-1) significantly stimulated the biosynthesis of PGE2 by a process that was potentiated by PHT. 6. Addition of exogenous arachidonic acid (AA) (greater than or equal to 1 microM) caused an increase of PGE2 formation in the fibroblasts that was not potentiated by PHT (20 micrograms ml-1). 7. The results indicate that treatment with PHT results in upregulation of prostaglandin biosynthesis in gingival fibroblasts challenged with IL-1 or TNF alpha, at least partly due to enhanced level of phospholipase A2 activity. PMID- 1504740 TI - Effects of nitric oxide synthesis inhibition on the goat coronary circulation under basal conditions and after vasodilator stimulation. AB - 1. The role of nitric oxide in the coronary circulation under basal conditions and when exposed to various vasodilator stimuli was studied in instrumented, anaesthetized goats, by examining the action of inhibiting endogenous nitric oxide production with NG-nitro-L-arginine methyl ester (L-NAME). 2. In 12 goats, left circumflex coronary blood flow (electromagnetically measured), systemic arterial blood pressure and heart rate were continuously recorded. L-NAME (3-4, or 8-10 mg kg-1 injected i.v.) decreased resting coronary blood flow by 20 and 28%, increased mean arterial pressure by 23 and 30% and increased coronary vascular resistance by 47 and 65%, respectively, without affecting heart rate, or blood gases or pH. These haemodynamic effects were reversed by L-arginine (200 300 mg kg-1 by i.v. injection, 5 goats). 3. Acetylcholine (0.001-0.1 micrograms), sodium nitroprusside (0.01-0.3 mg), and diazoxide (0.1-3 mg), injected intracoronarily in 6 goats, produced dose-dependent increases in coronary blood flow; sodium nitroprusside (0.1-0.3 mg) also caused hypotension and tachycardia. 4. During the effects of L-NAME, the coronary vasodilatation to acetylcholine was attenuated, to sodium nitroprusside was increased, and to diazoxide was unaffected, in comparison with control conditions. The hypotensive effects of sodium nitroprusside were also increased during treatment with L-NAME. 5. Graded coronary hyperaemic responses occurred after 5, 10 or 20 s of coronary occlusion. The magnitude of hyerpaemia for each occlusion duration was increased during treatment with L-NAME, in comparison to control.6. The results suggest: (a) endogenous nitric oxide is involved in regulation of coronary circulation by producing a basal vasodilator tone, (b) acetylcholine-induced coronary vasodilatation is mediated, in part, by nitric oxide, and (c) inhibition of basal endogenous nitric oxide production induces supersensitivity of coronary vessels to nitrovasodilators and enhances hyperaemic responses after short periods of ischaemia of the myocardium. PMID- 1504742 TI - Endothelin-1 inhibits PAF-induced paw oedema and pleurisy in the mouse. AB - 1. The current study analyses the effects of endothelin-1 (ET-1) on paw oedema and pleurisy induced by platelet activating factor (PAF) and other inflammatory agents in the mouse. 2. Combined subplantar injection of ET-1 (0.5 pmol/paw) did not modify oedema caused by histamine (1 to 100 mumol/paw), 5-hydroxytryptamine (1 to 100 mumol/paw) or bradykinin (1 to 100 nmol/paw) but markedly inhibited the response to PAF (0.95 to 3.8 nmol/paw). The selective action of ET-1 against PAF induced (1.9 nmol/paw) oedema was dose-dependent, reaching a maximum at 0.5 pmol/paw and lasted up to 2 h. 3. ET-1 (0.5 pmol/paw) also inhibited paw oedema (3-4 h) caused by zymosan (500 micrograms/paw). In contrast, it did not modify either the early (1-4 h) or late (48-72 h) phases of the oedematogenic response to carrageenin (300 micrograms/paw), when given either together with or 24 h after the carrageenin. 4. Intrathoracic injection of PAF (1.9 nmol/cavity) induced pleurisy characterized by an increase in pleural exudate volume, and in accumulation of Evans Blue which was maximal at 30 min and lasted up to 4 h. When injected together with PAF, ET-1 (0.5 pmol/cavity) virtually abolished PAF induced pleurisy. 5. It is concluded that ET-1 is a potent inhibitor of PAF induced inflammation in the mouse. Its mechanism of anti-inflammatory action in this species, in contrast to what has been found in other species, does not appear to derive from its potent vasoconstrictor properties as ET-1, at the doses used, failed to affect oedematogenic responses to other inflammatory mediators. PMID- 1504743 TI - Analysis of the depressant effect of the endothelium on contractions of rabbit isolated basilar artery to 5-hydroxytryptamine. AB - 1. The effects of endothelium removal and of a number of pharmacological agents known to modify endothelial cell function on the contractile response of rabbit isolated basilar arteries to 5-hydroxytryptamine (5-HT) and other vasoconstrictors were studied. 2. Endothelium removal slightly reduced the contractile response to potassium chloride (40 mM) but markedly augmented and potentiated contractions to 5-HT (1 nM-10 microM). 3. L-NG-nitro-arginine (L NOARG, 1-30 microM), an inhibitor of nitric oxide formation in vascular endothelial cells, evoked endothelium-dependent contraction, and augmented and potentiated contractions to 5-HT in endothelium-intact but not endothelium denuded tissues. Prior incubation with L-arginine (1 mM), but not D-arginine (1 mM), abolished these effects of L-NOARG (1 microM). L-NOARG (30 microM) also augmented contractions of endothelium-intact tissues to noradrenaline, prostaglandin F2 alpha, and to a lesser degree endothelin-1. 4. Neither glibenclamide (3 microM) nor N-ethylmaleimide (1 microM), putative inhibitors of the effects of endothelium-derived hyperpolarizing factor (EDHF) and of agonist stimulated endothelium-derived relaxing factor (EDRF) release respectively, had any effect on either resting tension or the contractile response to 5-HT. In some tissues indomethacin (3 microM), a cyclo-oxygenase inhibitor, produced a small contraction and augmented the contractile response to 5-HT, but in most cases indomethacin was without effect. 5. In endothelium-intact tissues precontracted with uridine 5'-triphosphate (UTP; 100 microM), 5-HT did not evoke relaxation but rather caused further contraction. Under the same conditions acetylcholine (0.01 10 microM) evoked endothelium-dependent relaxation.6. These data demonstrate that the endothelium profoundly depresses contractions of rabbit isolated basilar artery to 5-HT, and that this phenomenon can be fully accounted for by the release of an L-NOARG-sensitive relaxing factor. Neither glibenclamide-sensitive EDHF nor cyclo-oxygenase products plays a major role. As we could find no evidence that 5-HT stimulates the production of EDRF per se, and L-NOARG caused endothelium-dependent contraction and augmented contractions to other vasoconstrictor agents, it seems likely that a basal release of EDRF underlies this phenomenon. PMID- 1504745 TI - Steroid inhibition of oedema formation in the rat skin. AB - 1. A model has been developed to compare the inhibitory effects of the topical steroid, betamethasone-17-valerate, to those of systemically administered betamethasone upon oedema responses induced by 5-hydroxytryptamine (5-HT), platelet activating factor (PAF) and zymosan-activated serum (ZAS) +/- prostaglandin E1 (PGE1), measured in the rat skin by use of 125I-labelled human serum albumin. 2. Systemic betamethasone had a selective, time- and dose dependent inhibitory effect upon oedema treatment, with 1 mg kg-1 and a 3 h pretreatment having the greatest effect of the doses and times employed. 3. Topical betamethasone inhibited the oedema responses to all of the stimuli showing no apparent selectivity. 4. Topical betamethasone inhibits inflammatory stimuli in a different manner from systemic betamethasone. The broad spectrum of inhibition suggests that topical betamethasone acts by affecting a fundamental feature of the inflammatory response common to all of the stimuli. PMID- 1504744 TI - P2y purinoceptor responses of beta cells and vascular bed are preserved in diabetic rat pancreas. AB - 1. To investigate the effect of experimental diabetes on the P2y purinoceptor responses of pancreatic beta-cells and vascular bed, we used adenosine-5'-O-(2 thiodiphosphate) (ADP beta S), a potent and stable P2y agonist. This work was performed in the isolated perfused pancreas of the rat. 2. Diabetes was induced by streptozotocin (66 mg kg-1, i.p.). Five weeks after the induction of diabetes, on the day of pancreas isolation, the animals displayed marked hyperglycaemia (37.6 +/- 2.7 mM). Age-matched rats were used as controls. 3. Insulin response to a glucose stimulation from 5 to 10 mM was completely lost and stimulation of insulin release by the sulphonylurea, tolbutamide (185 microM), was drastically impaired in the diabetic pancreas (maximum responses were 1.5 +/- 0.4 and 7.0 +/- 1.4 ng min-1 for diabetic and age-matched rats respectively). 4. In contrast, in the diabetic pancreas ADP beta S (15 microM), infused in the presence of glucose 5 mM, elicited an immediate and significant insulin release similar to that observed in the age-matched pancreas (maximum responses were 7.6 +/- 1.5 and 6.7 +/- 1.3 ng min-1 respectively). This ADP beta S stimulating effect occurred independently of the glucose concentration (5, 8.3 and 28 mM) in the diabetic pancreas. On pancreatic vascular resistance, ADP beta S induced a similar vasodilatation in diabetic and age-matched rats. 5. In conclusion, ADP beta S retains its insulin stimulatory and vasodilator effects in experimental diabetes; P2y purinoceptors could therefore be considered as a new target for the development of antidiabetic drugs. PMID- 1504746 TI - The M3 muscarinic receptor links to three different transduction mechanisms with different efficacies in circular muscle of guinea-pig stomach. AB - 1. In a previous publication, we showed that 10 microM carbachol induced contraction by activating three independent transduction mechanisms in circular smooth muscle of guinea-pig gastric fundus (Parekh & Brading, 1991). These were: inositol trisphosphate-mediated intracellular Ca2+ release, Ca2+ influx through a nifedipine-sensitive route and Ca2+ influx through a receptor operated nifedipine insensitive pathway. The former two processes contribute to the phasic contraction and the latter two to the tonic contraction. In this paper, we have studied the effects of muscarinic receptor antagonists with known selectivity for different muscarinic receptor subtypes, on the contraction evoked by 10 microM carbachol. 2. Low concentrations of pirenzepine (M1 selective) had little effect on the contraction initiated by carbachol. Higher concentrations (greater than 1 microM) reduced only the phasic component. This concentration of pirenzepine greatly reduced the contraction evoked by 10 microM carbachol in Ca(2+)-free solution, indicating inhibition of intracellular Ca2+ release. 3. In the presence of 10 microM nifedipine, the tonic contraction evoked by 10 microM carbachol (reflecting the receptor-operated nifedipine-insensitive route) was abolished by 10 microM pirenzepine. In the absence of nifedipine pretreatment, however, 10 microM pirenzepine did not abolish the contraction to 10 microM carbachol. This contraction was subsequently abolished by nifedipine. 4. Only high concentrations (greater than 10 microM) of the M2-selective antagonist, gallamine, inhibited the contraction to 10 microM carbachol. Like pirenzepine, gallamine preferentially inhibited the phasic component of the contraction, indicating an effect on intracellular Ca2+ release. 5. The non-selective muscarinic receptor antagonist, atropine, abolished all components of the contraction. At low concentrations, atropine also reduced the phasic component without affecting the tonic one, indicating preferential inhibition of intracellular Ca2+ release.6. It is concluded that (i) the different transduction mechanisms have different sensitivities to the antagonists used and (ii) an M3 receptor activates the three transduction mechanisms with different efficacies. PMID- 1504747 TI - Effects of glucose, insulin or aldose reductase inhibition on responses to endothelin-1 of aortic rings from streptozotocin-induced diabetic rats. AB - 1. This study investigated the constrictor responsiveness to endothelin-1 (ET-1, 0.1 nM-0.1 microM) of aortic rings (under 10 g resting tension in Krebs solution) from 2- and 6-week streptozotocin (STZ, 60 mg kg-1, i.v.)-induced diabetic rats and vehicle-treated control rats. 2. In aortae from 2- and 6-week STZ-treated rats, and their corresponding controls, removal of endothelium caused leftward shifts of ET-1 concentration-response curves without affecting maximum responses. 3. Maximum responses to ET-1 were reduced in aortae from both 2- and 6-week STZ treated rats compared to those from control rats. Such reductions were still evident after removal of the endothelium. 4. Decreased responsiveness to ET-1 of aortae from 2-week STZ-treated rats was still evident after chronic treatment with the aldose reductase inhibitor epalrestat, but not after chronic insulin treatment or in aortae bathed in high glucose (30 mM) Krebs solution. 5. Decreased responsiveness to ET-1 of aortae from 6-week STZ-treated rats (compared with those from controls) was still evident after chronic epalrestat treatment and in high glucose Krebs solution. 6. These data suggest that the decreased responsiveness to ET-1 observed in aortae from 2- and 6-week STZ-induced diabetic rats is not due to abnormal activity of the polyol pathway. The altered responsiveness in aortae from 2-week diabetic rats (compared with those from control rats) may possibly be a manifestation of changes (adaptive or otherwise) which occur as a result of high glucose concentrations in vivo.However, in aortae from rats with diabetes of longer duration, other mechanisms may also play a role in the altered responsiveness, since it was no longer reversible by bathing in high glucose Krebs solution. PMID- 1504748 TI - Nitric oxide and sensory nerves are involved in the vasodilator response to acetylcholine but not calcitonin gene-related peptide in rat skin microvasculature. AB - 1. The contributions of sensory nerves and nitric oxide (NO) to vasodilator responses to acetylcholine (ACh) and calcitonin gene-related peptide (CGRP) were examined in rat skin microvasculature with a laser Doppler flowmeter to monitor relative blood flow. 2. Perfusion of ACh (100 microM; for 30 min) over a blister base on the rat hind footpad elicited microvascular vasodilatation and this response was not sustained. CGRP (1 microM; 10 min perfusion) also elicited vasodilatation and this response was maintained even when CGRP was no longer in contact with the blister base. 3. The vasodilator response to ACh was significantly smaller in rats pretreated as neonates with capsaicin to destroy primary sensory afferents than it was in age-matched controls. The vasodilator response to CGRP was unaffected by capsaicin pretreatment. 4. Selective inhibitors of NO synthase, NG-nitro-L-arginine (L-NOARG) and NG-monomethyl-L arginine (L-NMMA) (both at 100 microM) attenuated the vasodilator response to ACh in control rats, but had no effect on the vasodilator response to CGRP. There was a significant L-NOARG-resistant component in control rats while in capsaicin treated rats the vasodilator response to ACh was virtually abolished by L-NOARG. The inactive stereoisomer NG-monomethyl-D-arginine (100 microM) did not affect the vasodilator response to ACh. 5. The efficacy of L-NOARG and L-NMMA as inhibitors of endothelium-dependent responses was confirmed by use of an endothelium-dependent vasodilator, the calcium ionophore A23187 (100 microM; 10 min perfusion). Vasodilatation to A23187 was strongly attenuated by both L-NOARG and L-NMMA.6. These results suggest that sensory nerves and NO are both involved in the dilatation produced by ACh in rat skin microvasculature. A component of the vasodilator response elicited by ACh involves a direct action on the microvascular endothelium with subsequent generation of NO, while an additional component is elicited via activation of sensory nerves. The vasodilator mediator(s) released by ACh from sensory nerves acts largely independently of NO.7. The vasodilator response to CGRP is independent of a prejunctional action on sensory nerves and of NO. PMID- 1504749 TI - Inhibition of human neutrophil responses by alpha-cyano-3,4 dihydroxythiocinnamamide; a protein-tyrosine kinase inhibitor. AB - 1. Activation of neutrophils results in increased tyrosine phosphorylation of several proteins that may have important roles in receptor/effector coupling. In this study, the effect of a protein tyrosine kinase inhibitor on receptor mediated neutrophil activation by platelet-activating factor (PAF), leukotriene, B4 (LTB4) and N-formylmethionylleucylphenylalanine (FMLP) is investigated. 2. alpha-Cyano-3,4-dihydroxythiocinnamamide dose-dependently inhibited intracellular calcium release and superoxide generation from human neutrophils activated by 1 microM LTB4, PAF, and FMLP. 3. In the presence of cytochalasin B, FMLP stimulated elastase release from neutrophils was also inhibited to unstimulated levels by 5 min pretreatment with alpha-cyano-3,4-dihydroxythiocinnamamide. 4. The inhibitory action of alpha-cyano-3,4-dihydroxythiocinnamamide was found to be at or upstream of phospholipase C activation, blocking both phosphatidylinositol hydrolysis and protein kinase C activation. alpha-Cyano-3,4-dihydroxythiocinnamamide did not affect agonist receptor binding sites or receptor affinity in neutrophils. 5. Immunoblot analysis demonstrated the tyrosine phosphorylation of proteins of 41, 56, 66, and 104 kDa in neutrophils treated with agonists. Treatment of neutrophils with alpha-cyano-3,4-dihydroxythiocinnamamide prior to stimulation with chemoattractants reduced tyrosine phosphorylation of the above phosphoproteins. 6. These results indicate that alpha-cyano-3,4 dihydroxythiocinnamamide might be a useful agent in characterizing the essential proteins and biochemical pathways that regulate neutrophil activation. PMID- 1504750 TI - Prevention of intimal thickening after endothelial removal by a nonpeptide angiotensin II receptor antagonist, losartan. AB - 1. The present experiments were designed to investigate the role of local angiotensin II receptors in the myointimal proliferative response of the vascular wall after endothelial removal, by use of a novel, nonpeptide, angiotensin II receptor antagonist, losartan. 2. When administered 1 week before endothelial removal from the rabbit carotid artery and then continuously until animals were killed 6 weeks later, losartan in a dose of 10 mg kg-1 daily, p.o. had no significant effects on the carotid blood flow (CBF), mean arterial blood pressure (MBP) and heart rate (HR). 3. A full endothelial lining with increased density of regenerated endothelial cells was observed 6 weeks after the endothelial removal. These changes were unaffected by treatment with losartan. 4. Six weeks after endothelial removal, acetylcholine (ACh)- and adenosine diphosphate (ADP)-induced relaxations were greatly reduced though endothelial cells had regenerated. The reduction of the relaxations to these agonists were significantly restored by chronic treatment with losartan. The endothelial-independent, sodium nitroprusside (SNP)-induced relaxation remained unaffected in all groups. 5. There were no differences in the noradrenaline (NA)- and endothelin-1 (ET-1) induced contractions of the carotid artery strips between vehicle and losartan treated groups. In contrast, the contractile response of the strips to angiotensin II was significantly decreased in the losartan group, indicating the specific antagonism by chronic losartan against the angiotensin II receptor. 6. Six weeks after endothelial removal, marked myointimal proliferation resulting from new accumulation of proliferating smooth muscle cells and connective tissue was observed in the vehicle group. Losartan treatment greatly suppressed the myointimal proliferative response.7. These results suggest that the local angiotensin II receptors play a role in the myointimal proliferativeresponse of the vascular wall to removal of the endothelium. PMID- 1504751 TI - The effect of neosurugatoxin on the release of neurohypophysial hormones by nicotine, hypotension and an osmotic stimulus in the rat. AB - 1. Experiments were carried out to test whether neosurugatoxin (NSTX) which blocks autonomic ganglia also acts centrally, like hexamethonium, on nicotinic cholinoceptors involved in the neural control of release of vasopressin and oxytocin from the neurohypophysis. 2. In the water-loaded rat under ethanol anaesthesia, nicotine 100 micrograms i.v. produced a pressor and an antidiuretic response accompanied by an increase in the urinary excretion of vasopressin and of oxytocin-like radioimmunoreactivity (OLRI). This indicates release of both vasopressin and oxytocin. 3. Under conditions in which tachyphylaxis was avoided, NSTX, 80 ng i.c.v., caused a prolonged inhibition of the release of both hormones by nicotine. 4. NSTX i.c.v. caused some reduction in the pressor response to nicotine. It is suggested that this response involves both central and peripheral stimulation of the sympathetic nervous system and that the central component is blocked by neosurugatoxin. 5. Muscarine, 40 ng i.c.v., produced a pressor and an antidiuretic response with increased urinary excretion of vasopressin and OLRI. All these effects were blocked by atropine but were not inhibited by NSTX. 6. Sodium nitroprusside (SN), 200 micrograms i.v., and hypertonic saline (HS; 1.54 M NaCl solution) 4 microliters i.c.v., both produced antidiuretic responses accompanied by increased urinary excretion of vasopressin and OLRI. The ratio of the excretion of vasopressin to that of OLRI was 5.1 +/- 1.3 (mean +/- s.e.: n = 8) for SN and 1.2 +/- 0.24 (mean +/- s.e.: n = 6) for HS.NSTX 80 ng i.c.v., caused a significant reduction in the antidiuretic response to the hypotension induced with SN: the increased urinary excretion of vasopressin was also significantly reduced but not that of OLRI. NSTX had no effect on the response to HS.7. We conclude that NSTX acts centrally on nicotinic cholinoceptors to block the release of vasopressin and oxytocin by nicotine and the release of vasopressin, but not that of oxytocin, by hypotension. It does not inhibit the release of either hormone by a central osmotic stimulus. PMID- 1504752 TI - Identification and distribution of 5-HT3 recognition sites in the rat gastrointestinal tract. AB - 1. Tritiated derivatives of the potent and selective 5-HT3 receptor antagonists GR65630 and LY278584 were used to identify 5-HT3 recognition sites in the rat gastrointestinal tract. 2. Binding studies were carried out in homogenates of the rat oesophagus, the cardia, fundus, body and antrum of the stomach, regions of the small intestine, caecum and large intestine. The specific binding of a single concentration of GR65630 (0.5 nM) defined by granisetron (10 microM) in these areas indicated that the density of 5-HT3 recognition sites varied from 2.4 +/- 1.0 to 10.1 +/- 1.0 fmol mg-1 protein. 3. Saturable binding of [3H]-GR65630 could only be demonstrated in the terminal regions of the small intestine (Bmax in the range of 13.83 +/- 4.54-21.19 +/- 0.89 fmol mg-1 protein; mean +/- s.e. mean) and of high affinity (Kd in the range of 0.42 +/- 0.18-0.79 +/- 0.24 nM). Use of [3H] LY278584 revealed a similar binding density (Bmax 19.54 +/- 0.26 fmol mg-1 protein) and affinity (Kd 1.04 +/- 0.07 nM) in the terminal small intestine. 4. Binding of [3H]-GR65630 and [3H]-LY278584 to the terminal region of the small intestine was inhibited by 5-HT3 receptor ligands ondansetron and S-zacopride (and 5-hydroxytryptamine), but not by 5-HT1, 5-HT2, catecholamine, gamma aminobutyric acid and opioid receptor ligands. 5. These data demonstrate that there are regional variations in the density of 5-HT3 recognition sites within the rat gastrointestinal tract. Such data are relevant to the potential use of 5 HT3 receptor ligands to modify secretory and contraction responses in the gastrointestinal system. PMID- 1504753 TI - Effects of almitrine on the release of catecholamines from the rabbit carotid body in vitro. AB - 1. Almitrine increases ventilation by stimulating the carotid body (CB) arterial chemoreceptors but neither its intraglomic target nor its mechanism of action have been elucidated. 2. We have tested the hypothesis that chemoreceptor cells are targets for almitrine by studying its effects on the release of 3H catecholamines in an in vitro rabbit CB preparation. 3. It was found that almitrine (0.3 and 1.5 x 10(-6) M; i.e. 0.2 and 1 mg ml-1) increases the resting release of 3H-catecholamines from CBs (previously loaded with [3H]-tyrosine) incubated in a balanced 95% O2/5% CO2-equilibrated solution. 4. Almitrine at a concentration of 3 x 10(-6) M (2 mg l-1) also augmented the release of 3H catecholamines elicited by incubating the CBs in a hypoxic solution (equilibrated with 7% O2/5% CO2 in N2), by high external K+ (35 mM) and by veratridine (2 x 10( 5) M), but did not modify release induced by dinitrophenol (7.5 x 10(-5) M). 5. At the same concentration (3 x 10(-6) M), almitrine increased the rate of dopamine synthesis and was ineffective in modifying the cyclic AMP levels in either normoxic or hypoxic CBs. 6. It is concluded that chemoreceptor cells are the intraglomic targets for almitrine. The mechanisms of action of almitrine on chemoreceptor cells are discussed. PMID- 1504754 TI - An endothelial 5-HT receptor that mediates relaxation in guinea-pig isolated jugular vein resembles the 5-HT1D subtype. AB - 1. Endothelium-dependent and -independent, concentration-related, relaxations to 5-hydroxytryptamine (5-HT) are described in a preparation of guinea-pig isolated jugular vein. 2. An endothelial 5-HT receptor was studied in the presence of mesulergine (at 10.0 microM, a concentration sufficient to antagonize 5-HT2 receptor-mediated contractions and endothelium-independent relaxations to 5-HT). Relaxations mediated by the endothelial 5-HT receptor were resistant to antagonism by mesulergine. 3. Several 5-HT receptor agonists activated the endothelial receptor with the following rank order of potency: 5 carboxamidotryptamine (5-CT) greater than 5-HT greater than methysergide greater than or equal to alpha-methyl-5-HT greater than sumatriptan greater than 8 hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) greater than 2-methyl-5-HT. 4. Relaxations to 5-HT were not blocked by (+/-)-pindolol (1.0 microM), (-) propranolol (1.0 microM), spiperone (1.0 microM), ondansetron (1.0 microM) or ICS 205-930 (10.0 microM). 5. Both 5-HT and sumatriptan evoked endothelium-dependent relaxations which were sensitive to antagonism (pA2 and apparent pA2 values respectively) by methiothepin (8.1 and 8.6), metergoline (7.4 and 7.5), PAPP (8.2 and 8.2), yohimbine (7.1 and 6.8), rauwolscine (6.8 and 6.7), but not by corynanthine (10.0 microM). 6. These observations are consistent with a 5-HT1D receptor-mediated effect, and provide further support for the concept that differences exist between endothelial 5-HT receptors in different tissues and species. PMID- 1504755 TI - Construction of antagonist dose-response curves for estimation of pA2-values by Schild-plot analysis and detection of allosteric interactions. AB - 1. One aim of this paper is to show an alternative approach for the determination of antagonist affinity estimates, KB and pA2, by construction and evaluation of antagonist dose-response curves (DRCs), using the curve-fitting programme, ALLFIT. 2. Parallel antagonist DRCs were derived by vertical analysis of families of conventional agonist DRCs in the presence and absence of an antagonist at a certain agonist concentration above its ED50. The latter represents a chosen, i.e. fixed dose-ratio (DR). The antagonist concentration that reduces an agonist effect to its Emax/2 was termed Bx. It corresponds to B, the fixed antagonist concentration, tested to obtain DR-1, conventionally. 3. The dissociation constant was calculated as KB = Bx/DR-1, analogous to the conventional approach (KB = B/DR-1). Likewise, pA2-values were estimated by plotting log Bx, obtained by the alternative approach, vs log (DR-1) in an 'alternative Schild plot'. 4. Experimental agonist DRCs from our laboratory and from the literature were analysed and KB- and pA2-values obtained by the alternative approach were compared with those obtained by the conventional method. The results showed a very good agreement (correlation) between the pA2-values obtained by either method (slope = 1.02, r = 0.99, n = 9), in agreement with theoretical DRCs. 5. Besides estimation of KB and pA2, antagonist DRCs were also evaluated qualitatively. The most important finding was that allosteric antagonists or competitive antagonists with an allosteric component, such as gallamine, showed a significant reduction in the maximum of the antagonist DRCs (Imax). The evaluation of antagonist DRCs appears to be a sensitive procedure to detect allosteric interactions.6. This alternative approach can supplement or replace the conventional approach for the evaluation of antagonists on a quantitative and qualitative basis. The alternative approach appears of special advantage where the supply and/or the solubility of the agonist is limited, resulting in incomplete agonist DRCs.7. For rapid screening of potential antagonists, a single antagonist DRC at the maximum effective agonist concentration may be constructed to calculate KB reliably. PMID- 1504756 TI - Characterization of potassium currents modulated by BRL 38227 in rat portal vein. AB - 1. Smooth muscle cells of the rat portal vein were dispersed by enzymatic treatment and recordings of whole-cell membrane potassium currents were made by the voltage-clamp technique. In isolated cells by use of combined voltage- and current-clamp the effect of BRL 38227 on membrane potential and ionic currents was also studied. 2. BRL 38227 (0.1 to 10 microM) induced a non-inactivating potassium current (IKCO) which developed slowly (900 s to 300 s, respectively) to its full size. These effects of BRL 38227 were reversible. 3. In addition to its K-channel opening properties, BRL 38227 (1 to 10 microM) inhibited the amplitude and changed the activation and inactivation characteristics of a slowly inactivating, calcium influx-independent, outward potassium current (I(TO)). 4. Application of stationary fluctuation analysis to IKCO, showed a mean single channel current of 0.65 pA at -10 mV under a quasi-physiological potassium gradient. 5. In a combined voltage-clamp/current-clamp configuration, BRL 38227 (1 microM) induced a mean hyperpolarization of 22 mV. 6. The induction of IKCO by BRL 38227 and the associated hyperpolarization were suppressed by glibenclamide (1 to 10 microM) in a concentration-dependent manner. Glibenclamide (1 microM) had no effect on the inhibition of I(TO) by BRL 38227 (1 microM). PMID- 1504758 TI - Effect of 17 beta-oestradiol on contraction, Ca2+ current and intracellular free Ca2+ in guinea-pig isolated cardiac myocytes. AB - 1. The effect of 17 beta-oestradiol on cardiac cell contraction, inward Ca2+ current and intracellular free Ca2+ ([free Ca2+]i) was investigated in guinea-pig single, isolated ventricular myocytes. The changes of cell length were measured by use of a photodiode array, the voltage-clamp experiments were performed with a switch clamp system and [free Ca2+]i was measured with the Ca2+ indicator, Fura 2. 2. 17 beta-Oestradiol (10, 30 microM) caused a decrease in cell shortening at both 22 and 35 degrees C. This negative inotropic effect was accompanied by a decrease in action potential duration mainly brought about by a shortening of the plateau region of the action potential. 17 beta-Oestradiol (10, 30 microM) induced a similar decrease in cell shortening in voltage-clamped and current clamped cells. 3. In Fura-2 loaded cells, 17 beta-oestradiol (10 and 30 microM) decreased systolic Fura-2 fluorescence to 72 +/- 7% and 47 +/- 4% (n = 6, P less than 0.001) of control respectively. 17 beta-Oestradiol (10 microM) had no significant effect on diastolic Fura-2 fluorescence, but at higher concentration (30 microM) induced a slight decrease in resting Fura-2 fluorescence. The effect of 17 beta-oestradiol was reversible after 1-2 min of washout of the steroid. 4. 17 beta-Oestradiol (10 and 30 microM) decreased the peak inward Ca2+ current (ICa), which was sensitive to [Ca2+]o, dihydropyridines and isoprenaline, to 59 +/- 3% and 39 +/- 5% (n = 7 approximately 9, P less than 0.01) respectively, without producing any significant change in the shape of the current-voltage relationship.5. The recovery time of ICa from inactivation was delayed by 17beta oestradiol (10microM). The inhibitory effect of 17beta-oestradiol on ICa was less at a holding potential of -80 mV than at -40 mV.6. We conclude that 17beta oestradiol has a negative inotropic effect on guinea-pig single ventricular myocytes by inhibiting ICa and so reducing systolic [Ca2+]i. 17beta-Oestradiol may therefore have a Ca2+ channel blocking property in guinea-pig isolated ventricular myocytes. PMID- 1504757 TI - Responses to endothelins in the rat cutaneous microvasculature: a modulatory role of locally-produced nitric oxide. AB - 1. The response of the cutaneous microvasculature to intradermal injection of the endothelins (ET-1, ET-2 and ET-3) and the modulatory effect of endogenously produced nitric oxide (NO) have been determined in the rat. 2. Intradermal injection of endothelins (0.1- 10 pmol/site) induced dose-dependent local reductions in blood flow, measured by 133xenon clearance, with the following potency order; ET-1 = ET-2 greater than ET-3. 3. Laser Doppler blood flowmetry established that ET-1 (10 pmol/site) significantly (P less than 0.05) reduced microvascular blood flow for 3 h after injection. Over a wide dose-range, the response to the endothelins did not include any vasodilatation or visible flare. 4. A possible modulatory role of locally-produced NO was investigated by the intradermal injection of the potent inhibitor of NO generation NG-nitro-L arginine methyl ester (L-NAME). L-NAME (100 nmol/site) injected alone induced a significant decrease in blood flow. The vasoconstriction induced by L-NAME was partially reversed by L-arginine (P less than 0.05) but not observed with NG nitro-D-arginine methyl ester (D-NAME). 5. L-NAME significantly (P less than 0.05) enhanced the decrease in blood flow induced by submaximal doses of ET-1, ET 2 and ET-3 and vasopressin, although the results do not suggest that any of the vasoconstrictors stimulate NO release. The response to L-NAME was still observed 3.5 h after inducing a prolonged constriction with ET-1 (10 pmol/site).6. These results indicate that locally produced NO maintains a dilator tone in the cutaneous microvasculature of the rat and acts to modulate the effect of vasoconstrictors such as endothelins. Hence, it is suggested that in conditions where endogenous NO release is reduced, vasoconstrictor agents such as the endothelins could induce a dangerous decrease in blood flow possibly leading to ischaemia and tissue necrosis. PMID- 1504759 TI - Serotoninergic depression of auditory evoked responses recorded in the rat hippocampus: effect of repeated buspirone treatment. AB - Auditory evoked middle latency responses recorded in the hippocampus (HAER), were monitored in alert, gently restrained rats with chronic indwelling electrodes and cannulae. Intrahippocampal (i.h.) injection of 5-hydroxytryptamine (5-HT, 10 micrograms) reduced the amplitude and increased the latency of the N28 and P55 peaks of the HAER. An early (P18) negative peak was unaffected. Buspirone (1 microgram, i.h. and 3 mg/kg, i.p.) had similar effects to those produced by i.h. 5-HT. RU 24969 (1 mg/kg, s.c.) also reduced the amplitude of the N28 peak of the HAER. Long-term treatment with buspirone for 14 days at a dose (0.5 mg/kg, i.p.) which when applied acutely did not produce any observable effect, caused an increase in the latency of both the N28 and P55 peaks. Direct i.h. injection of 5 HT into these chronically treated animals did not have any additional depressant effect on the HAER peaks. It is concluded that these serotoninergic agonists can modulate the later peaks of the HAER possibly via 5-HT1A receptors. In the case of buspirone there was evidence of an enhanced depressant effect following chronic treatment [corrected]. PMID- 1504760 TI - Effects of phencyclidine on 5-hydroxytryptophan- and suckling-induced prolactin release. AB - The effects of acute and chronic exposure to phencyclidine (PCP) on the regulation of prolactin (PRL) secretion were examined. Female Sprague-Dawley rats were injected with PCP (10 mg/kg) or saline for 14 days, or just prior to the administration of the serotonin precursor, 5-hydroxytryptophan (5-HTP). A single injection of PCP had no effect on the 5-HTP-induced rise of plasma PRL levels. In contrast, chronic administration of PCP facilitated the release of PRL induced by 5-HTP. Peak plasma PRL levels were more than 3-fold higher after chronic PCP. The acute effect of PCP on suckling-induced PRL release was also examined. PCP delayed the rise of plasma PRL levels by suckling. The magnitude and profile of PRL, however, were similar to saline controls. The pups of PCP-treated dams failed to obtain milk during the suckling episode. Exogenous oxytocin restored the milk ejection reflex in PCP-treated dams. PCP had no effect on basal PRL release from anterior pituitary cells in vitro, and failed to alter the effects of TRH or dopamine. CONCLUSIONS: (1) chronic, but not acute, administration of PCP facilitates the 5-HTP-induced release of PRL, (2) acute exposure to PCP delays the suckling-induced rise in PRL and appears to inhibit oxytocin release. These data demonstrate that both acute and chronic PCP may alter the regulation of PRL release, likely through an indirect central mechanism. PMID- 1504761 TI - The effects of neurotensin on GABA and acetylcholine release in the dorsal striatum of the rat: an in vivo microdialysis study. AB - The effects of local perfusion with the tridecapeptide neurotensin (NT) on endogenous gamma-aminobutyric acid (GABA), acetylcholine (ACh) and choline release in the dorsal neostriatum were monitored using in vivo microdialysis in the halothane anaesthetized rat. The results show that NT (10 and 1000 nM) differentially regulates striatal GABA release without significantly influencing the release of either striatal ACh or choline. NT increased striatal GABA release both in the absence and presence of the ACh esterase inhibitor neostigmine (neo; 10 microM) in the perfusion medium. However, both basal GABA levels and responsitivity to NT were elevated in the presence of neo. The NT induced increase in striatal GABA release was reversed by the addition of tetrodotoxin (TTX; 1 micron) to the perfusion medium. These data suggest that (1) NT may play a role in modulating GABAergic neurotransmission in the dorsal neostriatum and (2) that the increase in GABA release may occur independently of an increase in the cholinergic component in the dorsal neostriatum, possibly via high affinity NT receptors located on striatal GABAergic neurons. PMID- 1504762 TI - EEG-dependent modulation of response dynamics of cat dLGN relay cells and the contribution of corticogeniculate feedback. AB - Single unit recordings were made extracellularly from the dorsal lateral geniculate nucleus (dLGN) in the anaesthetized and paralysed cat. The impulse rates of phasic (peak) and tonic components of visual responses to stimulation of the receptive field center by a flashing spot were determined during different states of the EEG, during local cortical cooling and during micro-iontophoretic application of the excitatory amino acid receptor agonists, quisqualate (QUIS) and N-methyl-D-aspartate (NMDA). Typically, visual responses were phasic during low frequency/high amplitude EEG patterns, resembling slow wave sleep (SWS). During high frequency EEG patterns (non-SWS) visual responses of X- and Y-cells exhibited a prominent tonic response component. This tonic component could be clearly reduced during ipsilateral cortical cooling in the non-SWS state. QUIS or NMDA, applied in order to mimic corticofugal activity, augmented the tonic response component, most efficiently during SWS EEG. The effects did not differ significantly for X- and Y-cells. During non-SWS EEG Y-cells exhibited a tonic response component similar to X-cells, but because of their higher peak rates the responses of Y-cells were on average more phasic than those of X-cells. Our results indicate that state-dependent changes in CNS activity modulate dL'GN responsiveness in part via the corticogeniculate feedback, and that predominantly the tonic response component is modulated. PMID- 1504764 TI - Neural correlates of genetically determined and acquired color preferences in quail chicks. AB - The uptake of tritiated 2-deoxyglucose (2-DG) was examined in brains of artificially selected and unselected control quail, in relation to genetically and environmentally variable early approach preferences of a colored stimulus. The data indicated high labeling in the tectofugal and low labeling in the thalamofugal projection systems in birds exhibiting preference for the light wavelength characteristics of the stimulus in independently tested choice situations. The differential labeling was observed regardless whether the stimulus preference was genetic or environmental in origin (i.e. whether it was exhibited by artificially selected and experientially naive or by unselected and imprinted control chicks). Chicks responding to the stimulus after prior imprinting experiences also exhibited high labeling in the intermediate medial portions of the neostriatum and hyperstriatum ventrale. PMID- 1504763 TI - A selective sexually dimorphic response in the median eminence neuropeptide Y. AB - Recent studies show that neuropeptide Y (NPY) is widely distributed in the hypothalamus and that it stimulates luteinizing hormone-releasing hormone (LHRH) release from the medial basal hypothalamus (MBH) of male and female rats. The neuroendocrine factors that regulate NPY neurosecretion in two sexes are not well understood. We have previously observed that orchidectomy (orch) in male rats decreased and testosterone (T) replacement increased NPY levels selectively in the median eminence (ME), arcuate nucleus (ARC) and ventromedial nucleus (VMN) and the KCl-evoked in vitro release of NPY from the MBH was likewise decreased after orch and restored by testosterone replacement. Now we report that these NPY responses are different in female rats following removal of the ovaries. Ovariectomy (ovx) decreased NPY concentrations in the ARC and VMN and not in the ME. Estrogen replacement restored NPY concentrations in the ARC and VMN, however, in the ME NPY concentration decreased significantly. Further, the KCl-evoked NPY release in vitro from either the MBH or ME of intact and ovx rats was similar. In an additional concurrent comparative study in male and female rats, we observed that of the 6 microdissected hypothalamic sites, NPY levels were approximately 50% less in the ME of intact females than in those of intact male rats. Again, in male rats there was a significant decrease in NPY levels in the ME, ARC and VMN after orch, whereas in female rats, NPY levels in the ARC and VMN, but not in the ME decreased after ovx.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1504765 TI - C-fos immunoreactivity in the brain following unilateral electrical stimulation of the dorsal periaqueductal gray in freely moving rats. AB - C-fos immunoreactivity was used to reveal brain areas in which neurons were influenced by electrical stimulations applied to the dorsal periaqueductal gray. These stimulations were applied in freely moving rats so that the resulting behaviors could be observed. Shortly afterwards, the brains of the rats were processed for C-fos immunoreactivity. In order to determine the specificity of the brain areas thus labeled, control stimulations were applied to the ventral tegmental area of other rats. Immunoreactive cells were found surrounding the tip of the stimulation electrode within a radius of 0.5 mm. This labeled area extended further along the rostro-caudal axis than along the medio-lateral or dorso-ventral axis in the periaqueductal gray. Distally, clusters of labeled cells were found ipsilaterally in the caudal periaqueductal gray extending to the nucleus cuneiformis, and bilaterally in the locus coeruleus and supramamillary decussation. More widespread labeling was found in most hypothalamic subareas and in the lateral habenula. The labeled brain areas following ventral tegmental area stimulations were totally distinct, and comprised the medial forebrain bundle, the nucleus accumbens, the vertical limb of the diagonal band and the medial septum. The pattern of labeling produced by periaqueductal gray stimulations was therefore specific, and provided information about brain structures involved in the motivational and behavioral effects of such stimulations. PMID- 1504766 TI - Membrane-bound choline acetyltransferase of the torpedo has characteristics of an integral membrane protein and can be solubilized by proteolysis. AB - Due to Triton X-114 fractionation of synaptosomes isolated from the electric organ of the fish Torpedo, the existence of a hydrophilic and an amphiphilic form of the enzyme choline-O-acetyltransferase (ChAT) was revealed. Amphiphilic ChAT which represents about 10% of total enzyme activity in synaptosomes, reached 40% of ChAT activity measured in preparations of synaptosomal plasma membranes (SPM) which were washed with solutions of increasing ionic strength. ChAT activity bound to washed SPM could be partially solubilized using proteinase K but not phospholipase C. No ChAT solubilization occurred by treating intact synaptosomes with proteinase K. Water/Triton X-114 partition coefficients of hydrophilic and amphiphilic ChAT were found to be 6.5 and 0.17, respectively. Sedimentation coefficients determined by centrifugation in linear density gradients of sucrose containing Triton X-100, were 4.2S and 4.4S for amphiphilic and hydrophilic ChAT, respectively. On the other hand, removal of Triton X-114 from the detergent phase containing amphiphilic ChAT activity led to enzyme aggregation. Finally, amphiphilic ChAT was slightly more acidic (pH 6.6) than was hydrophilic enzyme (6.8-7.0). We conclude that in Torpedo synaptosomes two forms of ChAT activity, a soluble and a membrane-bound form, are indeed present which differ in their hydrophobicity. The soluble form is hydrophilic. The membrane-bound form is amphiphilic and it aggregates upon removal of detergent. These are two characteristics of integral membrane proteins. Membrane-bound ChAT is most probably intracellularly oriented and not bound to membrane through a 'receptor' protein. PMID- 1504767 TI - Significance of an opiate mechanism in the adjustment of cerebrocortical oxygen consumption and blood flow during hypercapnic stress. AB - The role of adrenal medulla-derived enkephalins in the control of hypercapnic cerebrocortical blood flow (CBF) and oxygen consumption (CMRO2) was investigated in the ketamine anesthetized rat. Three experimental interventions were utilized: inhibition of opioid receptors with naloxone, decrease of adrenal enkephalin production with chronic adrenal medullectomy, and treatment of adrenal demedullated animals with the synthetic enkephalin analog, D-Ala2, N-Me-Phe4, Gly5-ol-enkephalin (DAGO). In intact, untreated animals hypercapnia increased CBF and CMRO2 by approximately 300 and 35%, respectively. Naloxone reduced the hypercapnic increase of CBF, and transformed the hypercapnic increase of CMRO2 into a decrease. The mid-points of the dose-response curves for (1)-naloxone and (d)-naloxone were 10 micrograms/kg and 100 micrograms/kg, respectively. Adrenal demedullation and treatment with (1)-naloxone (0.2 mg/kg) decreased the hypercapnic CBF and CMRO2 by approximately 50%. DAGO treatment of adrenal demedullated animals restored the hypercapnic CBF and CMRO2 to values similar to those found in intact animals. These observations suggest that opioid peptides (most likely adrenal medulla-derived enkephalins) play a significant role in the regulation of CMRO2 and CBF during moderate hypercapnia. PMID- 1504768 TI - Electrophysiology of dentate granule cells after kainate-induced synaptic reorganization of the mossy fibers. AB - Morphological data from humans with temporal lobe epilepsy and from animal models of epilepsy suggest that seizure-induced damage to dentate hilar neurons causes granule cells to sprout new axon collaterals that innervate other granule cells. This aberrant projection has been suggested to be an anatomical substrate for epileptogenesis. This hypothesis was tested in the present study with intra- and extracellular recordings from granule cells in hippocampal slices removed from rats 1-4 months after kainate treatment. In this animal model, hippocampal cell loss leads to sprouting of mossy fiber axons from the granule cells into the inner molecular layer of the dentate gyrus. Unexpectedly, when slices with mossy fiber sprouting were examined in normal medium, extracellular stimulation of the hilus or perforant path evoked relatively normal responses. However, in the presence of the GABAA-receptor antagonist, bicuculline, low-intensity hilar stimulation evoked delayed bursts of action potentials in about one-quarter of the slices. In one-third of the bicuculline-treated slices with mossy fiber sprouting, spontaneous bursts of synchronous spikes were superimposed on slow negative field potentials. Slices from normal rats or kainate-treated rats without mossy fiber sprouting never showed delayed bursts to weak hilar stimulation or spontaneous bursts in bicuculline. These data suggest that new local excitatory circuits may be suppressed normally, and then emerge functionally when synaptic inhibition is blocked. Therefore, after repeated seizures and excitotoxic damage in the hippocampus, synaptic reorganization of the mossy fibers is consistently associated with normal responses; however, in some preparations, the mossy fibers may form functional recurrent excitatory connections, but synaptic inhibition appears to mask these potentially epileptogenic alterations. PMID- 1504769 TI - TCP enhances the survival of human fetal spinal cord cells in culture. AB - Dissociated cell cultures were prepared from human spinal cords of 7-10-week-old fetuses. After 10 weeks progressive neuronal necrosis was observed in controls whereas N/1-(2-thienyl)cyclohexyl/piperidine (TCP) enhanced the survival time of the cells. After 21 weeks the number of gamma-aminobutyric acid (GABA)ergic and neuron specific enolase (NSE)-stained neurons was higher in the TCP-treated cultures than in controls. TCP appears to be a promising drug for long term survival of neurons. PMID- 1504770 TI - Serotonergic phase shifts of the mammalian circadian clock: effects of tetrodotoxin and high Mg2+. AB - The mammalian circadian clock in the suprachiasmatic nuclei (SCN) can be phase shifted in vitro by the serotonin agonist quipazine. Here we show that quipazine resets the SCN clock in the presence of tetrodotoxin or 10 mM Mg2+, treatments that block Na+ action potentials and Ca2+ channels, respectively. These results support the hypothesis that quipazine resets the clock by stimulating receptors located on clock elements rather than on cells afferent to the clock. PMID- 1504772 TI - Horseradish peroxidase labeling of growth cones and axons beyond the site of injury in injured rabbit optic nerve axons growing in their own environment. AB - Spontaneous growth of injured axons in the mammalian central nervous system is limited. We have previously shown an apparently regenerative growth of injured optic axons in the adult rabbit, achieved by supplying them with soluble substances originating from growing axons, followed by low energy helium-neon laser irradiation. The growing unmyelinated and thinly myelinated axons were embedded in astrocytes, and some were in the process of remyelination by oligodendrocytes. They were shown to have originated from the retinal ganglion cells. The present study further supports evidence relating to the origin and nature of these axons. Light microscopic analysis of these axons labeled with anterogradely transported horseradish peroxidase revealed that many of these axons have varicosities and bear growth cone-like swellings in their tips. These axons traverse the lesion site and extend into the distal stump in a disorganized pattern. PMID- 1504771 TI - 5 alpha-pregnane-3 alpha, 21-diol-20-one (THDOC) attenuates mild stress-induced increases in plasma corticosterone via a non-glucocorticoid mechanism: comparison with alprazolam. AB - 5 alpha-Pregnane-3 alpha,21-diol-20-one (THDOC; 5 mg/kg) and the triazolobenzodiazepine alprazolam (1 mg/kg) attenuated mild stress-induced increases in plasma corticosterone concentrations via GABAergic mechanisms. Unlike alprazolam, THDOC failed to decrease corticotropin-releasing factor (CRF) concentrations in the locus ceruleus. While THDOC may plausibly act via endogenous GABAergic mechanisms to reduce stress-induced endocrine and behavioral responses that are likely mediated in part by CRF neurons, these preliminary findings suggest that, at the dose and time point studied, THDOC does not identically mimic the actions of alprazolam, another drug which potentiates GABAergic activity. PMID- 1504773 TI - Protection against dendrotoxin-induced clonic seizures in mice by anticonvulsant drugs. AB - Various anticonvulsant drugs were evaluated for their ability to protect against clonic seizures induced in mice by intraventricular injection of the K+ channel blocking peptide dendrotoxin (DTX). Phenytoin, the phenytoin-like anticonvulsant carbamazepine and the broad spectrum drug valproate were effective in this model, whereas the GABA-enhancers diazepam and tiagabine, the NMDA antagonists (+/-)-CPP and (+)-MK-801, the AMPA antagonist NBQX, the antiabsence drug ethosuximide and the Ca2+ channel antagonist nimodipine were inactive. In contrast to the lack of activity of other NMDA antagonists, phencyclidine and ADCI [(+/-)-aminocarbonyl 10,11-dihydro-5H-dibenzo [a,d]cyclohepten-5,10-imine] were potent antagonists of DTX-induced seizures. PMID- 1504774 TI - Intracerebral transplants of primary muscle cells: a potential 'platform' for transgene expression in the brain. AB - After the transplantation of rat primary muscle cells into the caudate or cortex of recipient rats, the muscle cells were able to persist for at least 6 months. Muscle cells transfected with expression plasmids prior to transplantation were able to express reporter genes in the brains for at least 2 months. These results suggest that muscle cells might be a useful 'platform' for transgene expression in the brain. PMID- 1504775 TI - Kindling of the massa intermedia of the thalamus in rats. AB - The kindling response of the massa intermedia (MI) was assessed in rats. Clinical manifestation of the MI kindling was generally similar to that of limbic kindling, and positive transfer to the amygdala (AM) was obtained following MI kindling. However, MI kindling showed (1) a relatively high after discharge threshold which sometimes increased during the course of kindling, (2) a seizure stage instability with frequent regression to earlier stages, (3) a failure to establish a generalized seizure triggering threshold with an 'all-or-none' property, and (4) a generalized tonic-clonic seizure, which was quite different from a kindled limbic seizure, during early phase of kindling. Furthermore, the MI stimulation caused violent beating movement of the forelimbs, jumping, or running regardless of presence/absence of afterdischarge. The findings suggest that mechanisms other than a simple activation of limbic structures are involved in the process of MI kindling. PMID- 1504776 TI - Evidence that fine primary afferent axons innervate a wider territory in the superficial dorsal horn following peripheral axotomy. AB - Peripheral axotomy initiates changes in central primary afferent receiving areas of the dorsal horn of the spinal cord. Most of the presently known changes are degenerative in nature and consist of such things as cell and axon death or declines in peptides or enzymes. Other changes are regenerative in nature and because most of these occur in the superficial dorsal horn, which is where fine primary afferents end, we wished to ask whether peripheral axotomy results in a change in the distribution in these fine afferents. Using recently available markers for fine primary afferent axons and small dorsal root ganglion cells, we demonstrate that peripheral axotomy results in a considerable increase in the immunolabeled area for these compounds. Our interpretation is that there may be an extension of fine primary afferent fibers into lamina III and possibly lamina IV following peripheral axotomy. If further work bears out this conclusion, this would provide a possible explanation for the chronic pain states that sometimes follow peripheral nerve damage. PMID- 1504777 TI - Preservation of hippocampal brain slices with in vivo or in vitro hypothermia. AB - Hippocampal brain slices show CA1 injury similar to that seen after global ischemia in vivo. Cooling rats to 31 degrees C prior to sacrifice or cooling slices to 21 degrees C for 45 min increased the percentage of normal CA1 pyramidal cells after 5 h in vitro from 30% to over 80%. Brain slices also show a unique, consistent injury in dentate which is lessened by transient cooling to 21 degrees C but not by cooling the animal. PMID- 1504778 TI - Evidence for different sites of monoamine oxidase and catechol-O methyltransferase in the striatum. AB - Wistar rats were implanted with a probe for brain microdialysis in the striatum, and measured for two major dopamine metabolites, 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA). Intraperitoneal chlorpromazine (5 mg/kg) increased the concentrations of both metabolites in the dialysate when the determinations were carried out before 90 min after the administration. An apparent difference between the declines in concentrations of DOPAC and HVA was observed. Although the concentration of HVA maintained higher levels for over 6 h after the administration, DOPAC underwent a decrease in its concentration after the maximum level, which occurred at 90 min after the administration. These results are discussed in terms of the different distributions of two enzymes related to the metabolism of dopamine, catechol-O-methyltransferase and monoamine oxidase. PMID- 1504779 TI - Different effects of hypoxia on the membrane potential and input resistance of isolated and clustered carotid body glomus cells. AB - Intracellular recordings were made from cultured glomus cells of rat carotid bodies. Hypoxia (PO2 1-61 Torr), induced by Na-dithionite (Na2S2O4), differentially affected cells that were clustered and those that were isolated. More than 80% of clustered cells depolarized and their input resistance decreased, whereas about 60% of isolated cells hyperpolarized and their input resistance increased. In both groups, the mechanisms for cell depolarization or hyperpolarization appeared similar. Differences between clustered and isolated cells seemed to be conditioned by the sustentacular cells. Their processes surrounded clustered cells but were absent around isolated ones. However, we may have also functionally different glomus cells which may or may not correspond to the different types described by anatomists. PMID- 1504780 TI - Brown adipose tissue temperature responses following electrical stimulation of ventromedial hypothalamic and lateral preoptic areas or after norepinephrine infusion to Long Evans or Sprague-Dawley rats. AB - Thermoregulatory (brown adipose tissue temperature) experiments were conducted in age-matched anesthetized, male Sprague-Dawley and Long Evans rats kept at 37 degrees C given unilateral electrical stimulation of the ventromedial hypothalamic nucleus or the lateral preoptic area or after intravenous infusion of norepinephrine HCl (50 micrograms/kg total dose). Unilateral electrical stimulation (0.5 ms pulses of 250 microA at 50 Hz for 30 s) of the ventromedial nucleus or lateral preoptic area caused significant rises (greater than 0.6 degrees C) of intrascapular brown adipose tissue temperature in the Long Evans group only. Norepinephrine infusion (0.1 ml/min for 10 min), or intravenous bolus injection of propranolol HCl (2.5 mg/kg) caused significant yet similar increases (greater than 1.0 degrees C) and decreases (greater than -0.3 degrees C), respectively, of intrascapular brown adipose tissue temperature from pre administration control temperatures in both Long Evans and Sprague-Dawley groups. The results demonstrate that intrascapular brown adipose tissue sensitivity towards exogenous norepinephrine or propranolol administration is similar between Sprague-Dawley and Long Evans rats acclimated to 21 degrees C as determined by increases in temperature in the intrascapular brown adipose tissue pad. However, intrascapular brown adipose tissue thermogenesis of 21 degrees C-acclimated Long Evans rats is also activated after CNS electrical stimulation of the ventromedial nucleus or lateral preoptic area, an activation not seen in Sprague-Dawley rats suggestive that the latter group has some inhibition of neural pathways that activate brown adipose tissue thermogenesis. PMID- 1504781 TI - Acute and persistent effects of methamphetamine on developing monoaminergic neurons in reaggregate tissue culture. AB - Three-dimensional, rotation-mediated reaggregate tissue cultures composed of rostral mesencephalic cells and corpus striatal cells were used to examine the short-term and persistent effects of methamphetamine on developing monoamine containing neurons. Reaggregates were exposed to drug for one week. Reductions in reaggregate endogenous dopamine and serotonin levels occurred following treatment with methamphetamine during days 15-22 of culture over the concentration range 10(-7) to 10(-4) M. The highest methamphetamine concentration reduced dopamine and serotonin levels to 29 and 33%, respectively, of control values. Monoamine levels were reduced from control values after 3 days of exposure to 10(-4) M methamphetamine. No further reduction resulted from 4 additional days of drug treatment. In order to determine whether monoaminergic neurons would recover from the drug-induced deficit, reaggregates were exposed to 10(-4) M methamphetamine for 7 days and then grown in drug-free media for an additional 20 days. During the 20 day recovery period, monoamine levels in the control group increased with time in culture. After an initial rapid increase (recovery days 0-9), the level of monoamines in the recovery group remained at a constant proportion to the level in the control group suggesting that the monoaminergic neurons return to a rate of development similar to that seen in untreated cultures. However, this rate was not sufficient to overcome the reduction in monoamine levels produced by 7 days of methamphetamine treatment. The results indicate that the effects of methamphetamine on developing monoaminergic neurons are marked and persistent. PMID- 1504782 TI - Corticotropin-releasing factor mediated muscle atonia in pons and medulla. AB - The dorsolateral pontine inhibitory area (PIA) and medial medullary reticular formation (MMRF) have been found to mediate the muscle atonia of REM sleep. Our previous studies have shown that acetylcholine (ACh) microinjection in the PIA and in the nucleus paramedianus of the medial medulla produces muscle atonia. Glutamate microinjection in both PIA and nucleus magnocellularis (NMC) of the medial medulla also produces muscle atonia. Since immunohistochemical studies have identified corticotropin-releasing factor (CRF) as a potential dorsolateral pontine and NMC transmitter, the present study was undertaken to determine whether this transmitter could produce suppression of muscle tone. Experiments were performed on unanesthetized, decerebrated cats. CRF was microinjected into points in the PIA and NMC at which electrical stimulation produced bilateral inhibition of muscle tone. We found that CRF produced a dose-dependent muscle tone suppression. At 10 nM concentration, the latency and duration of muscle inhibition produced by CRF injection were comparable with those of L-glutamate, at 18.8 s and 4.1 min, respectively. This CRF-induced muscle inhibition was blocked by the CRF antagonist, alpha-helical [Glu27]corticotropin-releasing factor 9-41 (CRF 9-41). Microinjection of CRF and non-NMDA agonists, kainate and quisqualate, into the same sites in PIA and NMC produced muscle atonia. Pontine sites at which CRF injection induces atonia are identical to those at which acetylcholine microinjection produces atonia. These results indicate that CRF may interact with glutamate and acetylcholine in the generation of muscle atonia. PMID- 1504783 TI - Acute and prolonged effects of ibogaine on brain dopamine metabolism and morphine induced locomotor activity in rats. AB - Ibogaine, an indolalkylamine, proposed for use in treating opiate and stimulant addiction, has been shown to modulate the dopaminergic system acutely and one day later. In the present study we sought to systematically determine the effects of ibogaine on the levels of dopamine (DA) and the dopamine metabolites 3,4 dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) in tissue at several time points, between 1 h and 1 month post-injection. One hour after ibogaine-administration (40 mg/kg i.p.) a 50% decrease in DA along with a 37-100% increase in HVA were observed in all 3 brain regions studied: striatum, nucleus accumbens and prefrontal cortex. Nineteen hours after ibogaine-administration a decrease in DOPAC was seen in the nucleus accumbens and in the striatum. A week after administration of ibogaine striatal DOPAC levels were still reduced. A month after ibogaine injection there were no significant neurochemical changes in any region. We also investigated the effects of ibogaine pretreatment on morphine induced locomotor activity, which is thought to depend on DA release. Using photocell activity cages we found that ibogaine pretreatment decreased the stimulatory motor effects induced by a wide range of morphine doses (0.5-20 mg/kg, i.p.) administered 19 h later; a similar effect was observed when morphine (5 mg/kg) was administered a week after ibogaine pretreatment. No significant changes in morphine-induced locomotion were seen a month after ibogaine pretreatment. The present findings indicate that ibogaine produces both acute and delayed effects on the tissue content of DA and its metabolites, and these changes coincide with a sustained depression of morphine-induced locomotor activity. PMID- 1504784 TI - 5-HT2 receptors in the nucleus tractus solitarius: characterisation and role in cardiovascular regulation in the rat. AB - The effects of the local application of drugs acting on 5-HT2 receptors in the nucleus tractus solitarius (NTS) on the heart rate and blood pressure were investigated in normal and nodose ganglionectomized anaesthetized rats. The unilateral micro-injection of an agonist such as 2,5-dimethoxy-3-bromo amphetamine (DOB) (0.1-0.5 pmol) or 2,5-dimethoxy-3-nitroamphetamine (DON) (0.1 0.5 pmol) produced a dose-dependent hypotension and bradycardia in both intact and ganglionectomized animals. These cardiovascular effects were similar to those observed after the unilateral micro-injection of low doses (pmol) of 5-HT, and could be prevented by the prior micro-injections of the 5-HT2 antagonists ketanserin, ritanserin and piremperone. These findings support the hypothesis that 5-HT2 receptors within the NTS play a role in the reflex regulation of blood pressure. In addition, it was also observed that the micro-injection of subthreshold doses of 5-HT or DOB significantly enhanced the hypotension and bradycardia produced by the unilateral micro-injection of N-methyl-D-aspartate (NMDA). The potentiation of NMDA depressor effects by 5-HT or DOB could be totally prevented by ketanserin or piremperone, suggesting that 5-HT acting upon 5-HT2 receptors in the NTS may intervene in the reflex control of blood pressure by modulating the glutamatergic transmission. PMID- 1504785 TI - Is CNS trauma a prerequisite for the elongation of CNS axons into denervated peripheral nerve? AB - The demonstration that some central nervous system (CNS) axons can regenerate when provided with a suitable environment raises the possibility of new treatments for CNS injury. However, at present the conditions for optimal regeneration are not well understood. For example, the methods used in previous studies have entailed CNS trauma as part of the research protocol (e.g. that resulting from the implantation of peripheral nerve grafts), and so the role of neuronal or axonal injury in the regrowth observed has been difficult to establish. To determine whether such injury is necessary for the central reinnervation of denervated peripheral nerve, the L5 dorsal root has been chronically denervated in rats by freeze-thawing its dorsal root ganglion (DRG), and the root has been left attached to either traumatized or non-traumatized spinal cord. The trauma induced was quite mild, and resulted from several vertical insertions of a fine needle. Two to 4 months later, retrogradely transported horseradish peroxidase (HRP) was used to label spinal neurons which sent axons into the denervated roots. HRP-labelled neurons were found in each of the spinal cords subjected to trauma, but no labelled neurons were observed in any of the non-traumatized cords. The number of HRP-labelled neurons in individual spinal cords was positively correlated with the degree of spinal cord trauma. We conclude first that the chronic and intimate presence of a denervated PNS tissue in continuity with the spinal cord is not, in itself, a sufficient stimulus to induce its reinnervation by CNS axons. Second, we conclude that under the conditions of this experiment CNS trauma is a prerequisite for the reinnervation of denervated peripheral nervous tissue by CNS axons. PMID- 1504786 TI - Differential sites of origin and collateralization of corticospinal neurons in the rat: a multiple fluorescent retrograde tracer study. AB - Cells of origin for corticospinal fibers in the rat were identified following retrograde transport of Fluoro-Gold (FG), Propidium iodide (PI), Fast blue (FB), and Diamidino yellow (DY) injected unilaterally into lumbar (FG), mid-thoracic (PI), cervical enlargement (FB), and cranial cervical (DY) spinal gray matter. Most labeled neurons were contralateral to injection in lamina V and ranged from small to very large. These cells occupied two distinct cortical regions: one rostral and the other larger and more caudal. Neurons of the rostral region projected axons solely to cervical spinal segments whereas neurons of the caudal region projected fibers to all spinal segments. Somatotopically, most neurons projecting to lumbar segments were most medial. More than 98% of all labeled cortical neurons contained only a single fluorescent tracer; however, within a single tissue section each of the 4 tracers could be found in these single labeled neurons. The few double labeled neurons contained only cervical (DY + FB) or thoracolumbar (PI + FG) tracers. No triple or quadruple labeled cells were seen. Hence morphological evidence is presented that corticospinal axons branch to terminate in more than one spinal region, but these collateral terminations are restricted to only a few adjacent spinal segments. PMID- 1504787 TI - Distribution of cannabinoid receptors in rat brain determined with aminoalkylindoles. AB - Extensive mapping of the cannabinoid receptor in rat brain has been reported recently using synthetic cannabinoids. Another class of compounds, the aminoalkylindoles (AAIs), does not resemble the cannabinoids structurally. Ligand binding data on isolated membranes, however, indicate that AAIs bind to the cannabinoid receptor. The present experiments compared the binding of AAIs and synthetic cannabinoids in vitro and by receptor autoradiography. The AAIs bound to a receptor in rat cerebellum with high affinity (Kd = 15 nM), and synthetic cannabinoids were potent competitors for AAI binding sites. In the autoradiographic studies in rat brain, an AAI and a synthetic cannabinoid were used to compete for the binding of a radiolabeled AAI to compare regionally and quantitatively the inhibition of AAI binding by the two classes of compounds. The distribution of the AAI binding was very similar to that reported for synthetic cannabinoid binding. These data add further evidence that the aminoalkylindoles bind to the cannabinoid receptor. Furthermore, the autoradiographic data for AAI binding, in addition to the autoradiographic data for the synthetic cannabinoid, provide a high degree of confidence in the localization of the cannabinoid receptor in the rat brain. PMID- 1504788 TI - Amphiphilic behavior of a brain tetrameric acetylcholinesterase form lacking the plasma membrane anchoring domain. AB - We have studied the behavior of a mammalian brain tetrameric acetylcholinesterase (AChE) form released by proteinase K from a crude membrane fraction of bovine caudate nucleus. The solubilization of active AChE indicated the presence of a protease-sensitive site in the anchored protein. Unexpectedly, the solubilized AChE maintained its capacity to form aggregates in detergent-free gradients. We demonstrate here that this property was due neither to the presence of the hydrophobic membrane-anchoring domain still linked to the enzyme, nor to the presence of AChE activity trapped in small plasma membrane vesicles. Moreover, we found that the proteinase K-treated extract, devoid of AChE activity, induced the aggregation of purified hydrophilic AChE which usually does not form aggregates. Our results suggest the presence of an AChE aggregating factor in bovine brain extracts prepared in the presence of proteinase K. It is possible that this aggregation may reflect a process of AChE clustering on neurons. PMID- 1504789 TI - Infusions of 6-hydroxydopamine into the nucleus accumbens abolish the analgesic effect of amphetamine but not of morphine in the formalin test. AB - The effects of bilateral infusions of 6-hydroxydopamine into the nucleus accumbens on analgesia produced by D-amphetamine and morphine were examined, in separate experiments, in the formalin test in rats. The lesions in the two experiments were not significantly different and dopamine in the nucleus accumbens, olfactory tubercle and striatum was depleted to 21.1%, 40.3% and 65.0% of control values, respectively. D-Amphetamine (0.75 and 2.0 mg/kg) and morphine (3.0 and 6.0 mg/kg) attenuated the response to formalin in unlesioned control rats. The analgesic effect of amphetamine was severely reduced by 6 hydroxydopamine lesions, and the residual analgesia was correlated with the amount of dopamine in the nucleus accumbens, but not with dopamine levels in the olfactory tubercle or striatum. Lesions also attenuated the locomotor stimulant effect of amphetamine. The analgesic effect of morphine was not altered by 6 hydroxydopamine infusions, nor was there any correlation between the analgesic effect of morphine and dopamine concentration in the nucleus accumbens, olfactory tubercle or striatum. The results indicate that the dopamine innervation of the nucleus accumbens is not critical for the analgesic effect of morphine but plays a major role in the analgesic effect of amphetamine. PMID- 1504790 TI - Insulin-like peptide(s) in the central nervous system of the snail Helisoma duryi. AB - The central nervous system of the snail Helisoma duryi contains porcine insulin immunoreactive cells. Most of these cells are known as neurosecretory mediodorsal cells (MDC), and are involved in regulation of growth. There are about 25-40 large and small MDC in each cerebral ganglion near the commissure. Besides the MDC, 6-8 insulin-immunoreactive cells are also seen in the left parietal ganglion and the visceral ganglion. Insulin-immunoreactive material can be traced from the MDC perikarya into their axons in the median lip nerve. The elementary granules of the MDC are 150-250 nm in diameter, and are insulin-immunoreactive. Insulin like material is released by the CNS in vitro, and can be measured by radioimmunoassay using an antiserum against human insulin. High potassium and 4 aminopyridine increase such release in vitro. It is likely that insulin-like peptide is a growth hormone in H. duryi. PMID- 1504791 TI - Chronic neonatal MK-801 treatment results in an impairment of spatial learning in the adult rat. AB - Chronic neonatal treatment with the non-competitive N-methyl-D-aspartate (NMDA) receptor antagonist MK-801 from postnatal day 8 through 19 has been shown to affect hippocampal NMDA receptor function of adult rats. Since many studies have shown that NMDA receptors play a crucial role in learning and memory, and since one of the hippocampal functions is spatial learning, we have examined whether this changed response of hippocampal neurons is associated with changes in its normal function. We therefore tested spatial learning and memory using a water maze in adult rats neonatally treated with MK-801. MK-801-treated rats were able to learn the spatial task as well as control rats but at a significantly slower rate. Performance in a visual cue task was not affected by the neonatal treatment, suggesting that the slower spatial learning is not caused by locomotor or sensory deficits. These results suggest that chronic NMDA receptor blockade during the neonatal period leads to long-lasting disturbances of hippocampal function. PMID- 1504792 TI - The effects of A- and C-fiber stimulation on patterns of neuropeptide immunostaining in the rat superficial dorsal horn. AB - The present study determines the effects of sciatic nerve stimulation at intensities that activate A-fibers alone or both A- and C-fibers on immunostaining for substance P (SP), cholecystokinin-octapeptide (CCK-8), galanin (GAL), dynorphin (DYN) and vasoactive intestinal polypeptide (VIP) in the superficial dorsal horn of the rat spinal cord. The goal of this study is to provide a more precise spatial localization of the sites of release or accumulation of these compounds in relation to specific types of stimuli. Following A-fiber stimulation, there was no significant change in immunostaining for any of these compounds. However, A- and C-fiber stimulation resulted in major changes. For SP, CCK-8, GAL and DYN there was a large and significant loss of immunostaining in medial regions of the dorsal horn. This is the area where sciatic nerve primary afferent fibers terminate and the depletion is probably correlated with activity in these fibers. By contrast, VIP immunostaining is increased in the lateral part of the superficial cord, which is outside of the central sciatic afferent fiber terminations. This indicates that the increase is not in the fine sciatic sensory axons that are directly stimulated. As a final point, the fact that C-fiber but not A-fiber stimulation causes marked changes in the immunocytochemical distribution of all these compounds is further evidence, albeit indirect, that they are involved in nociceptive information processing. PMID- 1504793 TI - Electrophysiological and anatomical studies on thalamic mediodorsal nucleus projections onto the prefrontal cortex in the cat. AB - Electrical stimulation of the mediodorsal nucleus (MD) of the thalamus elicited field potentials in the gyrus proreus (PRO), frontalis (FR), rectus (RE) and cinguli anterior (CIant) of the ipsilateral prefrontal and adjacent cortical areas in cats. The results of a laminar field potential analysis indicate that the field potentials can be regarded as a combination of deep and superficial thalamocortical responses. By injecting horseradish peroxidase (HRP) into the MD, HRP-labeled terminals were distributed in the prefrontal and adjacent cortical areas where the field potentials were elicited. Densely labeled terminals in cortical layer I were distributed where the superficial thalamocortical responses were prominent, while those in layers III-V were distributed in the areas where the deep thalamocortical responses were prominent. PMID- 1504794 TI - Correlation between the induction of an immediate early gene, zif/268, and long term potentiation in the dentate gyrus. AB - Expression of the immediate early gene zif/268 (also termed NGFI-A, Krox 24, TIS8 and Egr-1) was investigated in awake rats following various long-term potentiation (LTP) induction protocols. zif/268 mRNA (Northern blots) and protein (immunohistochemistry) levels sharply increased following LTP, and followed a time course characteristic of other immediate early genes. When measured across 3 tetanization protocols known to produce differing degrees of LTP persistence, zif/268 induction was found to be more highly correlated with LTP duration than with the magnitude of initial LTP. These data support the hypothesis that the immediate early gene zif/268 plays a role as a third messenger in the cascade of cellular and nuclear events that govern the persistence of LTP. PMID- 1504795 TI - Ibotenic acid lesions in the amygdaloid central nucleus but not in the lateral subthalamic area prevent the acquisition of differential Pavlovian conditioning of bradycardia in rabbits. AB - The present study examined the effect of ibotenic acid lesions in the amygdaloid central nucleus (ACe) or in the lateral zona incerta of the subthalamus (LZI) on the acquisition of differential Pavlovian conditioning of bradycardia in rabbits. Previous work has shown that bilateral electrolytic lesions in either ACe or LZI abolished the retention of conditioned heart rate (HR) responses. In order to determine whether these findings were due to destruction of cells intrinsic to ACe or LZI, ibotenic acid lesions were placed bilaterally in either structure or in control sites. Following recovery, animals were subjected to differential Pavlovian conditioning in which one tone (CS+) was paired with periorbital shock and a second tone (CS-) was presented alone. It was found that destruction of cell bodies in ACe, but not LZI, prevented the acquisition of the differential bradycardiac conditioned response. In addition, ACe lesions did not interfere with baseline HR, the HR orienting response, the HR unconditioned response to shock, or the concomitantly conditioned corneoretinal potential. The results of this study suggest that destruction of cells intrinsic to ACe selectively prevents the acquisition of differentially conditioned HR, and perhaps other conditioned responses related to conditioned arousal, but does not affect unlearned HR responses or specific somatomotor conditioned responses. PMID- 1504796 TI - Male rat copulation following 6-OHDA lesions of the medial preoptic area: resistance to repeated administration and rapid behavioral recovery. AB - Dopamine (DA) in the medial preoptic area (MPOA) has been shown to facilitate male rat sexual behavior. However, injections of the catecholamine (CA) neurotoxin 6-OHDA into the MPOA did not impair copulation in tests 3 days after injection. In the present study, three weekly (serial) injections produced no copulatory deficits compared to animals that received a single injection or to preinjection copulatory behavior scores. However, blocking CA synthesis, which did not impair control rats, produced deficits in both single and serial lesion animals, with significantly fewer serial than single lesion animals initiating copulation. Biochemical analysis of tissue punches showed no difference in MPOA concentrations of dopamine, norepinephrine, epinephrine, or the dopamine metabolite DOPAC between the two groups. Additional animals were tested at earlier intervals after 6-OHDA injections into the MPOA. Tests conducted 30 min after an MPOA injection of 6-OHDA revealed that all measures of copulation were impaired, relative to scores 24 h later. However, these scores were not significantly different from animals tested 30 min after a vehicle injection. A final group, tested 4 h after injection, showed impairment of all measures of copulation compared to vehicle injections and to tests 24 h later. Furthermore, in the tests 24 h later, 6-OHDA animals were not different from vehicle animals. Results from all experiments show that 6-OHDA injections into the MPOA impair copulation for at least 4 h, but that behavioral recovery is complete 24 h later. However, deficits can be reinstated by inhibiting DA synthesis, suggesting that increased synthesis in undamaged terminals contributed to behavioral recovery. PMID- 1504797 TI - The effect of stimulus duration on noxious-stimulus induced c-fos expression in the rodent spinal cord. AB - C-fos is a proto-oncogene that is expressed within some neurons following depolarization. The protein product, fos, has been proposed as an anatomical marker for neuronal activity following noxious peripheral stimulation. However, the literature on noxious-stimulus induced fos expression contains several puzzling observations on the time course and laminar distribution of neuronal labeling within the spinal cord. This study has analyzed the effect of stimulus duration on the expression of fos-like immunoreactivity (FLI) within the spinal cord of anesthetized rats. In order to examine the time course of fos expression following brief periods of stimulation, we required a type of stimulus that was intense enough to activate nociceptors but that did not produce tissue damage. We have therefore employed pulsed, high intensity electrical stimulation, with stimulus durations ranging from 3 s to 24 h. The results indicate that stimulus duration has a profound effect upon the number of labeled cells, the intensity of neuronal labeling, the laminar pattern of FLI, and the time course of fos expression. Brief stimulation periods induce relatively few and relatively lightly labeled neurons, located predominantly within the most superficial laminae of the dorsal horn. Maximal immunoreactivity appears approximately 2 h after stimulation has ceased, and disappears within hours. Continuous stimulation produces many more labeled cells, darker labeling, and FLI within both dorsal and ventral laminar regions. Maximal FLI is seen after approximately 4.5 h of continuous stimulation, with reduction in the number of labeled cells thereafter. These data indicate that the results of any study employing c-fos as a marker for neuronal activity may be affected by the duration of the exciting stimulus. PMID- 1504798 TI - Impulses of variable amplitude recorded from cell-attached patches on small hippocampal neurons. AB - Small cultured neurons from embryonic rat hippocampus were investigated with the cell-attached configuration of the patch-clamp technique. The currents associated with spontaneous cellular impulse generation were studied. The positive peak current amplitudes varied by a factor larger than 2.5 for 11 of 12 cells quantitatively investigated, suggesting underlying action potentials of variable amplitude. A simple RC-network was found to describe the properties of the patch membrane, and was used to calculate the underlying potential time course. The action potentials computed showed a considerable variation in amplitude. The results suggest that the impulse variability previously analysed with the whole cell technique was not caused by dialysis of the cell interior. PMID- 1504799 TI - Myoclonus in the decerebrate cat produced by gallamine. AB - After intravenous infusion maintaining a neuromuscular blocking concentration very little gallamine enters the cerebrospinal fluid (CSF) of the intact anesthetized cat even after several days. After a similar intravenous infusion in the decerebrate cat gallamine enters the CSF slowly over 4 days eventually reaching a concentration similar to that in the plasma. This procedure is accompanied by very strong twitching in many muscles and the occurrence of slow waves in the inferior olive in synchrony with the twitches. A large dose (4 mg) of gallamine triethiodide injected directly into the cisterna magna of an intact anesthetized cat produced twitching within 1 min and slow waves in the inferior olive in good synchrony with the twitches; the effects lasted at least 43 h. Injection of a quantity of gallamine triethiodide (about 130 micrograms) sufficient to mimic the concentration in the CSF obtained after 3-4 days of neuromuscular block in the decerebrate cat (50-120 micrograms/ml gallamine) had extremely weak effects lasting for at most 1 h. However, this weak effect is probably due to the anesthetic because injection of a similar quantity into an (unanesthetized) decerebrate cat at any time after decerebration had strong effects. After intracisternal injection of gallamine the concentration in the CSF reaches very low levels within 12 h but twitching and activity in the inferior olive persists for 1-2 days. The reasons for this prolonged action are now being investigated. The effects of gallamine are compared with the condition of reticular reflex myoclonus. PMID- 1504800 TI - Protective effects of brain hypothermia on behavior and histopathology following global cerebral ischemia in rats. AB - The present experiments were designed to assess whether brain hypothermia can reduce the behavioral and histopathological deficits associated with global forebrain ischemia. Animals were subjected to 12.5 min of four vessel occlusion (4VO) with moderate hypotension, and brain temperature maintained at either 37 degrees C (4VO-37) or 30 degrees C (4VO-30). Behavioral tests designed to assess forelimb reflexes and sensorimotor function were given on post-operative weeks 2 and 4. Beginning in week 5, the rats were trained on a variety of navigation problems in the Morris water maze. Histopathological examination of the tissue 2 months following reperfusion revealed that 4VO-37 animals sustained substantial cell death in hippocampal region CA1 and moderate damage to the dorsolateral neostriatum. 4VO-30 animals showed minimal cell death in CA1 and neostriatum. There were no group differences for any of the sensorimotor measures, or for acquisition performance on either the simple place task or visible platform version of the water maze. In contrast, during acquisition of the learning set task, the performance of 4VO-37 animals was impaired relative to either of the other groups, whereas the performance of 4VO-30 animals was not significantly different from the sham controls. These data suggest that moderate intra-ischemic brain hypothermia provides long-lasting protection from behavioral deficits as well as neuronal injury following transient global ischemia. PMID- 1504801 TI - Cortical input to parvalbumin-immunoreactive neurones in the putamen of the squirrel monkey. AB - The cortex projects heavily to the striatum and makes asymmetrical synaptic contact mainly with the spines of medium-sized densely spiny neurones. The possibility exists that corticostriatal terminals also make synaptic contact with classes of striatal interneurones. The primary objective of the present experiment was to determine whether parvalbumin-immunoreactive neurones, which represent a class of GABAergic interneurones in the striatum, also receive a direct synaptic input from corticostriatal fibres. The anterograde tracer biocytin was injected into the motor and premotor cortices of the squirrel monkey (Saimiri sciureus). Following perfuse-fixation, sections of the striatum were processed histochemically to reveal the transported biocytin using an avidin biotin-peroxidase complex and diaminobenzidine as the chromogen. They were then immunostained to reveal parvalbumin using benzidine dihydrochloride as the chromogen. In both the light and electron microscopes, the morphological features and the afferent synaptic input of the parvalbumin-immunoreactive neurones were similar to those observed in other species. Similarly, the morphology and postsynaptic targets of the corticostriatal terminals were similar to those described in other species. Light microscopic examination revealed that the anterogradely labelled corticostriatal terminals were often in close apposition to the parvalbumin-positive neurones. At the electron microscopic level the biocytin-positive corticostriatal terminals were found to make asymmetrical synaptic contacts mainly with spines. The parvalbumin-positive neurones were seen to have an invaginated nucleus, extensive cytoplasm and relatively few spines. Parvalbumin-immunoreactive dendrites received a dense synaptic input consisting mainly of asymmetric synapses and only a few symmetric synapses. Biocytin labelled corticostriatal terminals were often seen in asymmetrical synaptic contact with parvalbumin-immunoreactive dendrites. These results show that GABAergic interneurones identified on the basis of parvalbumin immunoreactivity, in addition to the projection neurones of the striatum, are under the direct influence of the cerebral cortex. PMID- 1504802 TI - A novel monoclonal antibody against carbohydrates of L1 cell adhesion molecule causes an influx of calcium in cultured cortical neurons. AB - We have studied the function of carbohydrates of the L1 molecule, a member of the immunoglobulin superfamily of adhesion molecules, using a novel monoclonal antibody, mAb-L1(2E12), against L1 molecule. This antibody was specific for the 200 kDa component of mouse L1 molecule and its epitope was N-linked for complex type oligosaccharides. The mAb-L1(2E12) was found to induce a rise in intracellular Ca2+ concentration ([Ca2+]i) in cultured mouse embryonic cortical neurons. The rise in [Ca2+]i was dependent on the concentrations of mAb-L1(2E12). The rise seemed to be due to an influx of extracellular Ca2+ as EGTA treatment abolished it. Both cadmium and nifedipine blocked the effect of mAb-L1(2E12), suggesting the Ca2+ influx was through voltage-operated Ca2+ channels, particularly L-type Ca2+ channels. These results provide an important insight for understanding the mechanisms by which oligosaccharides of the L1 molecule influence various functions of neural cells. PMID- 1504803 TI - Neural and endocrine sensitivities to opioids decline as a function of multiparity in the rat. AB - Hormonal changes during pregnancy regulate the onset of maternal behavior at parturition. In addition, the concentrations of beta-endorphin and mu opioid receptors are higher during pregnancy and lower during lactation. Previous studies have shown that sensitivity of female rats to the disruptive behavioral effects of morphine changes as a function of the number of pregnancies and/or lactations the females undergo. The objectives of the present study were to determine whether central infusions of the endogenous opioid, beta-endorphin, would disrupt maternal behavior. Next, we investigated the possibility that the neural sensitivity to beta-endorphin changes with repeated pregnancies. And finally, we examined whether opioid-mediated endocrine responses also change as a function of multiparity. In the first study, bilateral infusions of low doses (0.06-0.72 nmol) of beta-endorphin into the medial preoptic area (MPOA) of lactating, primiparous rats disrupted maternal behavior. When comparable doses of beta-endorphin were infused into the MPOA of age-matched, multiparous rats, the behavioral effects of beta-endorphin were significantly attenuated. In response to suckling stimulation, an opioid-mediated endocrine response, primiparous mothers secreted more prolactin than did multiparous rats. Moreover, multiparous, but not primiparous, mothers were insensitive to the ability of naloxone, an opiate antagonist, to block suckling-induced increases in prolactin. These findings indicate that reductions in neural sensitivity to opioids develop as females undergo repeated pregnancies and lactations, changes which affect both behavioral and endocrine functions. PMID- 1504804 TI - The functional anatomy of manual motor behavior after unilateral frontal lobe lesions. AB - In normal brains different behavioral tasks lead to increased metabolism in different loci. Resting monkeys with acute hemineglect following periarcuate lesions show deficient glucose utilization (LCGU) in motor thalamus and other loci of the hemisphere with the lesion. To determine if the abnormal LCGU could be altered by a specific behavioral task, we used behavioral testing and training, and quantitative 2-deoxyglucose (2-DG) autoradiography. Animals reached criterion in a bimanual traction task (BMTT), then were tested for hand preference and responses to sensory stimuli, and received unilateral frontal or sham lesions. Operated animals showed hemineglect, and, on BMTT, intermanual coordination errors. 2-DG of frontals at rest showed deficient LCGU in 4 of 7 thalamic, and 1 of 4 cortical regions assessed. In contrast, only 2 thalamic and no cortical regions were deficient in pulling animals. Thus, in the face of structural damage and distant deficient neural activation, performance of a specific behavioral task may increase metabolism in specific brain loci, implying that plasticity of neural activation vis-a-vis behavioral demand is present even acutely after brain injury. PMID- 1504805 TI - Evoked responses from an in vitro slice preparation of a primary gustatory nucleus: the vagal lobe of goldfish. AB - The vagal lobe of goldfish (Carassius auratus) is a laminated structure in which primary gustatory afferents terminate in a stereotypical pattern. Because the afferent fibers enter and distribute within the lobe in the transverse plane, the structure appeared suitable for in vitro slice electrophysiology. Slices were cut on a vibratome at 400-800 microns thickness and placed in a fresh water teleost Ringer's solution. Following a recovery period, clear population responses were recorded following electrical stimulation of the incoming fiber bundle. The later two components of this evoked waveform were eliminated by removal of the calcium from the bathing solution indicating the synaptic origin of these potentials. Further, the waveform was highly dependent on the position of the recording electrode, both in terms of laminar and tangential position. Evoked response maxima corresponded to the layers in which the primary afferent fibers terminate. In addition, the maximal evoked response was limited to a tangential distance of approximately 100 microns. The spatial restriction of the evoked waveform therefore corresponds well with the known anatomical organization of the primary gustatory afferent fibers. The evoked waveforms are sensitive to stimulus repetition rate, being facilitated by stimulus trains less than 50 ms in duration and fatigued by stimulus repetitions as slow as 1 Hz. This in vitro preparation should provide a means for investigating the physiological and pharmacological properties of primary gustatory fibers and nuclei. PMID- 1504806 TI - Morphological and functional development of the suprachiasmatic nucleus in transplanted fetal hypothalamus. AB - The development of the suprachiasmatic nucleus (SCN) in fetal rat hypothalamus transplanted to the adult brain was studied using morphological and functional methods. Anterior hypothalamic tissue was transplanted into the third ventricle, lateral ventricle or subarachnoid space of intact, adult hosts from E17 fetuses. These transplants developed the cytoarchitectonic and immunohistochemical staining characteristics of SCN, clusters of parvocellular neurons expressing vasopressin- and vasoactive intestinal polypeptide-like immunoreactivity in adjacent cellular populations, irrespective of the exact location of the transplanted tissue in the host brain. The functional status of the transplants placed in the rostral third ventricle and the foramen of Monroe was analyzed and compared to host SCN using in vitro recording of neuronal firing rate and measurement of metabolism using the 2-deoxyglucose (2-DG) technique. During subjective day, neuronal firing rates and 2-DG uptake were high in discrete cell groups within the transplants which were subsequently demonstrated to exhibit the cytoarchitectonic and immunohistochemical characteristics of SCN. The firing rates and 2-DG uptake in these areas were lower during the subjective night. This pattern of activity closely resembles that of the intact SCN. In contrast, neither transplanted anterior hypothalamic area, lacking an identifiable SCN-like structure, nor posterior hypothalamic area showed day-night differences in firing rate or 2-DG uptake. These observations indicate that SCN transplanted into intact adult hosts exhibits morphological and functional differentiation nearly identical to the host and that the transplanted SCN maintains circadian function which is probably entrained to the host SCN. PMID- 1504807 TI - Plasminogen activators in the neuromuscular system of the wobbler mutant mouse. AB - Wobbler, the neurological mutant mouse, carries an autosomal recessive gene (wr) and has been characterized as a model of lower motoneuron disorders with associated muscle atrophy, denervation and reinnervation. During normal murine neuromuscular development a decrease in muscle plasminogen activator (PA) activity accompanies synapse maturation. In contrast, experimental denervation in adult mice leads to an increase in muscle PA activity. The purpose of the present study was to determine the possible involvement of PAs in the denervation/reinnervation phenomena and motoneuron degeneration that characterize the wobbler mutant mouse. We determined the degree of innervation and its characteristics in wobbler mice by measuring choline acetyltransferase (ChAT) activity. We measured ChAT in the spinal cord as well as in two different muscles known to be differentially affected, biceps brachii and gastrocnemius. We found a sharp decrease of ChAT activity in both muscles but not in spinal cord extracts. We estimated the extent of sprouting by the silver/cholinesterase stain. Motoneuron terminal sprouting, not detected in normal animals, was present in 40% of the neuromuscular junctions in wobbler mice. We estimated specific PA activities in biceps brachii and gastrocnemius muscle extracts, as well as spinal cord extracts, using both an amidolytic assay and fibrin zymography. Increased PA, predominantly urokinase-PA (uPA), was observed in wobbler mouse muscle. A greater uPA was detected in biceps brachii muscle than in gastrocnemius muscle, which is less impaired by the mutation. There was no change in spinal cord PA, although tissue type PA (tPA) is the predominant PA type there.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1504808 TI - Modulation of net outward current in cultured neurons by angiotensin II: involvement of AT1 and AT2 receptors. AB - In this study we have used whole-cell, voltage-clamp procedures to determine the effects of angiotensin II (AII) on net outward current (I(no)) in neurons co cultured from the hypothalamus and brainstem of 1-day-old rats. Ino is the sum of all inward and outward membrane currents (minus Na+, which is blocked by tetrodotoxin) which occur during the repolarization phase of the action potential. We have determined that AII elicits two separate effects on I(no) in cultured neurons. AII caused a reversible and concentration (0.1 nM-10 microM) dependent increase in I(no). This effect is inhibited by the AT2 receptor selective antagonists, PD123177 and PD123319 (both 100 nM), but not by the AT1 selective receptor blocker, DuP753 (Losartan; 100 nM), and so it is mediated by AT2 receptors. In a smaller number of neurons AII induced a reversible and concentration (0.01 nM-10 microM)-dependent decrease in I(no) that was blocked by Losartan (100 nM) but not by PD123177 (100 nM). Thus the decrease in I(no) is mediated by AT1 receptors. Additionally, some neurons displayed both AT1- and AT2 receptor-mediated effects on I(no). Our results demonstrate two distinct actions of AII on membrane ionic currents in cultured neurons, effects that are mediated by different AII receptor subtypes. PMID- 1504810 TI - Effect of chronic pre- and post-natal low-dose ethanol exposure on brain enolase isoenzyme activities. AB - Sprague-Dawley dams were treated with 3 v/v % ethanol in liquid diet from the 8th day gestation through 3 weeks nursing period. Offsprings, ages 1, 2 and 3 weeks, and their dams were studied. Brain weights and their total proteins were not affected by this ethanol treatment. Total enolase activity/mg protein and its isoenzymes, i.e. non-neuron-specific, hybrid and neuron-specific, (mumol/min/mg protein) in 100,000 g supernate, were significantly lower in the treated. Additionally, enolase isoenzyme transformation was delayed. PMID- 1504809 TI - The effects of ibotenate lesions of the median preoptic nucleus on experimentally induced and circadian drinking behavior in rats. AB - Male Sprague-Dawley rats were injected with either ibotenic acid or vehicle in the region of the median preoptic nucleus (MnPO) during methoxyflurane anesthesia. Later, the rats were tested for drinking responses elicited by angiotensin II (1 and 2 mg/kg s.c.) and hypertonic saline (3 and 6% w/v s.c.). Tests were conducted at 3 different phases of a 12:12 light-dark (LD) cycle (in the middle of the light phase and in the early and midportion of the dark phase). The rats with ibotenate lesions of the MnPO drank significantly less than vehicle injected and lesion control groups regardless of when the tests were conducted. Subsequent monitoring of the diurnal rhythm of drinking, employing electrical lickometers, detected no difference between the rhythms of 4 rats with ibotenate lesions of the MnPO who failed to drink to homeostatic challenges and 4 vehicle injected control rats. The results indicate that ibotenic acid lesions of the MnPO block drinking behavior stimulated by angiotensin II and hypertonic saline without disrupting the entrainment or pattern of ad libitum drinking. PMID- 1504811 TI - Differential effects of right-sided and left-sided orchidectomy on lateral asymmetry of LHRH cells in the mouse brain. AB - Luteinizing hormone-releasing hormone (LHRH) immunoreactive cells were found to be more numerous in the right side of the brain than in the left in male mice. Bilateral orchidectomy or removal of the right testis decreased the number of LHRH cells, while removal of the left testis failed to cause any changes in the number of LHRH cells. The results indicated a clear left-right difference in the neuroendocrine regulation of gonadal function in male mice. PMID- 1504812 TI - Effects of Ca2+ antagonists and aminoglycoside antibiotics on Ca2+ current in isolated outer hair cells of guinea pig cochlea. AB - The effects of various Ca2+ antagonists and aminoglycoside antibiotics on the Ca2+ channel in isolated outer hair cells of the guinea pig were investigated using a whole-cell patch-clamp technique. The inhibitory action was in the order of La3+ much greater than Cd2+ much greater than Ni2+ greater than Co2+ for inorganic Ca2+ antagonists, and flunarizine = nicardipine greater than omega conotoxin greater than methoxyverapamil = diltiazem much greater than amiloride for organic ones. Aminoglycoside antibiotics also had antagonistic effects on the Ca2+ channel. PMID- 1504813 TI - Enhancement of acetylcholine release during REM sleep in the caudomedial medulla as measured by in vivo microdialysis. AB - Previous studies in our laboratory have found that muscle atonia could be triggered by two distinct areas of the medial medulla, a caudal region, corresponding to the nucleus paramedianus (NPM) and a rostral region, corresponding to the nucleus magnocellularis (NMC). The former region is responsive to acetylcholine (ACh) and the latter region is responsive to glutamate. In this study we have measured the endogenous ACh release across the sleep-wake cycle in these two areas with the microdialysis technique in unanesthetized, freely moving cats. We found that ACh release in NPM was state dependent and was about 30% higher (P less than 0.001) during rapid eye movement (REM) sleep than during slow-wave sleep and wakefulness. However, ACh release in NMC was not selectively elevated in REM sleep. The enhancement of ACh release in NPM during REM sleep supports our hypothesis that ACh release onto cholinoceptive neurons in this area mediates the muscle atonia of REM sleep. PMID- 1504814 TI - The neuroprotective actions of 2,3-dihydroxy-6-nitro-7-sulfamoyl benzo(F)quinoxaline (NBQX) in a rat focal ischaemia model. AB - The neuroprotective effects of NBQX, a selective antagonist for the AMPA/kainate subtype of excitatory amino acid receptors, were investigated in a rat focal ischaemia model, involving permanent occlusion of the left middle cerebral artery (MCA). NBQX (3, 10 or 30 mg/kg) was administered i.v. immediately after MCA occlusion and again 1 h later. The highest dose of NBQX (2 x 30 mg/kg) gave significant protection against hemispheric (24%) and cortical (27%) ischaemic damage. The lower doses of NBQX (2 x 3 or 2 x 10 mg/kg) were ineffective. No protection was seen against caudate damage for any of the doses of NBQX tested. NBQX has a t1/2 of 30 min, therefore, a second experiment was done in which a dose of 30 mg/kg was given as an i.v. bolus followed immediately by an infusion of 10 mg/kg/h for 4 h, dosing was started immediately after MCA occlusion. This dosing regimen resulted in a mean plasma level over the 4 h of 17 micrograms/ml, and significant protection against the volume of hemispheric (29%) and cortical (35%) ischaemic damage, which was slightly better than that achieved with two bolus doses of 30 mg/kg. Once again no protection was seen against caudate damage. We conclude that NBQX, an AMPA/kainate antagonist was neuroprotective in a focal ischaemia model in the rat. PMID- 1504816 TI - Neuronal multipotentiality: evidence for network representation of physiological function. AB - Extracellular action potentials of single neurons in motor cortex and rectified and integrated electromyographic activity (EMG) of gastrocnemius and anterior tibialis were recorded while a monkey performed isometric ankle plantar and dorsal flexion tasks. This study determined the consistency of neuronal behaviors across different tasks. Methods characterized neuronal behaviors by determining which behavioral event within a single task, such as the appearance of the 'go' signal, force onset, or agonist and antagonist EMG onset, was best related to changes in neuronal activity. Another method compared the temporal profiles of discharge modulation across different tasks. Of 220 neurons recorded, 44 were selected because they were consistently active in the tasks. Of these, 37 were in the precentral cortex and the remaining seven were in the postcentral cortex. Only 14 of the 33 in motor cortex were consistent in their behavioral correlations. Several had multiple changes in activity within a single task that were related to different behavioral events. Half were consistent for direction of force and a third were consistent for magnitude of force. Furthermore, there was little consistency in the temporal profiles of discharge activity for all 44 neurons across tasks. Similar modulations of discharge activity among neurons in one task were different in another task. Such inconsistencies are evidence against the cardinal cell hypothesis of physiological representation. We offer a new hypothesis analogous to connectionism in parallel distributed processing. PMID- 1504815 TI - Cholinergically induced REM sleep triggers Fos-like immunoreactivity in dorsolateral pontine regions associated with REM sleep. AB - We sought to determine the presence of Fos-like immunoreactive (Fos-LI) cells in the pontine brainstem following cholinergically induced sustained rapid-eye movement (REMc) sleep in cats. Microinjections (0.25 microliter) of vehicle (N = 2) or carbachol (2.0 micrograms/0.25 microliter; N = 4) were made into the medial pontine reticular formation. Carbachol produced a state with all the signs of natural REM sleep and with durations of 15.2-57.8 min. Compared with vehicle control animals, carbachol treated animals showed a significantly higher number of Fos-LI cells in pontine regions implicated in REM sleep generation, with longer REMc bouts associated with more Fos-LI cells than the short-duration bout. Regions with REMc-associated Fos-LI increases included: the lateral dorsal tegmental (LDT) and pedunculopontine tegmental (PPT) nuclei, where some Fos-LI cells were immunohistochemically identified as cholinergic; the locus coeruleus, where some of the Fos-LI cells were identified to be catecholaminergic; the dorsal raphe and the pontine reticular formation. These findings suggest immediate early gene activation is associated with the ubiquitous biological state of REM sleep. PMID- 1504817 TI - Repeated injections of cocaine inhibit the serotonergic regulation of prolactin and renin secretion in rats. AB - Alterations in serotonergic function following repeated cocaine injections were examined using neuroendocrine responses to a serotonin (5-HT) releaser and 5-HT agonists. Forty-two hours following administration of cocaine (1-15 mg/kg i.p.) twice daily for 7 or 30 days, male Sprague-Dawley rats were injected with the 5 HT releaser p-chloroamphetamine (PCA; 8 mg/kg i.p.) and blood samples were collected 1 h later for radioimmunoassays of plasma prolactin, plasma renin activity (PRA) and plasma renin concentration (PRC). PCA significantly increased secretion of prolactin and renin. These responses were attenuated in rats pretreated with cocaine for 30 days. In rats receiving cocaine for 7 days, the attenuation of PCA-induced secretion of prolactin and renin was less consistently observed. To determine whether these alterations were due to pre- or postsynaptic effects, rats were injected with cocaine (15 mg/kg i.p.) twice daily for 7 days, and the neuroendocrine responses to the direct 5-HT agonists RU 24969 and m-CPP were examined, 42 h after the last cocaine injection. Pretreatment with cocaine potentiated RU 24969-induced stimulation of plasma prolactin concentration. However, cocaine did not alter the ability of m-CPP to increase plasma prolactin concentrations. The stimulation of renin secretion in response to both 5-HT agonists was not altered by cocaine pretreatment. The data suggest that repeated cocaine impairs the function of serotonergic nerve terminals that regulate these endocrine responses. Furthermore, the 5-HT receptors that mediate prolactin secretion may exhibit supersensitivity. PMID- 1504818 TI - Vasopressin-containing neurons of the suprachiasmatic nuclei inhibit corticosterone release. AB - The suprachiasmatic nucleus (SCN) is the major pacemaker in the central nervous system responsible for generating circadian rhythmicity in mammals. Tracer studies show limited projections of the SCN, mainly to the paraventricular nucleus of the thalamus and paraventricular and dorsomedial nuclei of the hypothalamus, suggesting that the latter two areas may be the target areas of the SCN for controlling corticosterone release. The present results show that when infused in the paraventricular/dorsomedial nucleus of the hypothalamus femtomolar concentrations of vasopressin (VP), but not vasoactive intestinal peptide (VIP), are able to suppress elevated levels of corticosterone in SCN-lesioned animals to basal daytime values. On the other hand, infusion of the VP antagonist in the same hypothalamic area induced a sevenfold increase of basal corticosterone levels in intact animals. The SCN origin of this VP input was established in SCN lesioned animals where no difference between the effect of infusing the antagonist or Ringer could be detected. These results imply that the SCN can influence the daily corticosterone rhythm through its VP-containing projection to the paraventricular/dorsomedial nucleus of the hypothalamus. PMID- 1504819 TI - Maintenance and synthesis of proteins for an anucleate axon. AB - The anucleate (distal) segment of a crayfish medial giant axon (MGA) remains intact for months in vivo after severing the axon from its cell body, a phenomenon referred to as long-term survival (LTS). We collected axoplasm from chronic anucleate MGAs by perfusing 2-cm lengths of axons with an intracellular saline. This axoperfusate was analyzed by SDS-PAGE and silver stained. Axoperfusate proteins from intact MGAs and from chronic anucleate MGAs exhibiting LTS for up to 6 months were the same. Furthermore, immunoreactive levels of actin and beta-tubulin were similar in axoperfusates from intact and chronic anucleate MGAs. This maintenance of proteins in chronic anucleate MGAs must be due to a lack of protein degradation and/or to local protein synthesis by a source other than the cell body. To investigate local protein synthesis in vitro, we added [35S]-methionine to the extracellular saline surrounding intact and chronic anucleate MGAs. After 4- to 6-h incubations, radiolabelled proteins were detected in axoperfusates analyzed by SDS-PAGE and fluorography. The similarity between radiolabelled proteins in axoperfusates and MGA glial sheaths indicated a glial origin for the radiolabelled axoperfusate proteins. Various observations and control experiments suggested that glial-axonal protein transfer occurred by a physiological process. Glial-axonal protein transfer may contribute to the maintenance of proteins during LTS of chronic anucleate MGAs. PMID- 1504820 TI - Ventral pontine catecholaminergic pathway mediates the vasopressin response to splanchnic osmostimulation in conscious rats. AB - This study examines the role of catecholamines, cell bodies and fibers of passage within the subcoeruleus area (subLC) in the arginine vasopressin (AVP) response to splanchnic osmotic stimulation and hemorrhage. Bilateral chemical lesions were induced into the subLC, approximately 1 mm ventral to the locus coeruleus (LC), using 6-hydroxydopamine (6-OHDA) and ibotenic acid to selectively destroy catecholaminergic components and cell bodies, respectively. Vehicle and 5,7 dihydroxytryptamine (5,7-DHT) injections into the subLC area, 6-OHDA injections into the LC, as well as systemic desipramine pretreatment, were performed as controls for the possible non-specific effects of the lesions. Seven and 8 days later, plasma AVP level, plasma osmolality, mean arterial pressure and heart rate were measured following either gastric infusion of hypertonic (598 mOsm/kg; 2 ml/4 min) or isotonic (290 mOsm/kg) saline or a mild hemorrhage (2.5 ml/300 g) in conscious rats with indwelling tail artery catheters and naso-gastric tubes. 6 OHDA injections into subLC reduced the AVP response to the osmotic stimulation by 62.3% (P less than 0.01), as compared to vehicle-injected controls. These same rats demonstrated a normal AVP response to hemorrhage implying a specificity of the disrupted pathway. All controls confirmed that the effects of the 6-OHDA were due to specific action on noradrenergic components within the subLC area. Ibotenic acid lesions in the subLC did not significantly decrease the AVP response, demonstrating that mainly fibers and not cell bodies in this region are part of the pathway. 6-OHDA injections just anterior to the LC, where the dorsal noradrenergic bundle (DNAB) forms, reduced the AVP secretion due to hemorrhage by 77.0% (P less than 0.05), but had minor effects on the response to osmotic stimulation. These results indicate that catecholaminergic fibers travelling primarily within the subLC, in the ventral noradrenergic bundle (VNAB), carry splanchnic osmotic input to the hypothalamus, whereas the DNAB may mediate the AVP response to hemorrhage. PMID- 1504821 TI - Disappearance of circadian rhythms in Parkinson's disease model induced by 1 methyl-4-phenyl-1,2,3,6-tetrahydropyridine in dogs. AB - Administration of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) to dogs produces clinical, pathological and neurological features in dog resembling human Parkinson's disease. Using this animal model, we studied the changes in diurnal rhythms of urine volume, creatinine in urine, and vasopressin, aldosterone and renin activity in plasma. Before MPTP treatment, urine volume showed a peak between 17.00 and 1.00 and plasma vasopressin concentration also showed a clear circadian rhythm with a peak at 13.00 and a minimum level at 5.00. Two weeks after MPTP treatment (2.5 mg/kg i.v.), the rhythm of urine volume disappeared and that of vasopressin became less clear. Plasma renin activity increased 2 and 4 weeks after MPTP treatment. The increase was, however, not enough to change the concentration of plasma aldosterone. We examined the effect of L-3,4 dihydroxyphenylalanine (levodopa), on the circadian pattern of urine volume and vasopressin attenuated by MPTP. Levodopa (4 mg/kg/day) was administered orally every day from the first week after MPTP treatment. The circadian rhythms of urine volume and vasopressin reappeared within one week after the start of levodopa administration. PMID- 1504822 TI - Intraretinal xenografts of differentiated human retinoblastoma cells integrate with the host retina. AB - We report on the successful use of chemically modified Y79 human retinoblastoma cells for intraretinal xenografting into damaged adult mammalian eyes. Y79 cells were exposed in vitro to retinoic acid/butyrate to induce differentiation. Using a multisite transplantation method, the suspension was injected into the subretinal space of Fischer 344 rats. The survival, integration, and differentiation potential of these cells was studied, following their return to the intraocular milieu from which the progenitor cells originated. The grafted cells survived and differentiated into immature photoreceptor elements in the subretinal and intraretinal locations, as multiple clusters of rosette-forming cells intimately attached to the host neuroretina. The differentiation process included development of synaptic connectivity of the ribbon type with the surrounding neuropil. No signs of renewed cell division were found within grafts performed on 42 rat eyes, and there was no indication of cell-mediated host reaction against the transplants. This study indicates that tumorigenicity can be suppressed in mitotically arrested Y79 cells, and that these cells are capable of undergoing differentiation in vivo. This provides evidence of the remarkable differentiation properties of human retinoblastomas while indicating that Y79 cells may ultimately be able to substitute for fetal cells in experimental retinal transplantation. PMID- 1504823 TI - The effects of lesions of the habenular nuclei on the development of sensitization to the behavioral activational effects of repeatedly administered morphine in the rat. AB - The effects of lesions of the habenular nuclei on the development of sensitization to the behavioral activational effects of morphine (MOR), administered repeatedly either systemically or directly into the ventral tegmental area (VTA) were examined. Lesions of the habenular nuclei blocked the early-appearing sedative effects and enhanced the later-appearing locomotor activational effects seen after systemic injections of MOR (10 mg/kg, i.p.). Habenular lesions did not potentiate the development of sensitization to the locomotor-activational effects seen with the repeated, systemic administration of MOR. The bilateral injection of MOR (5.0 micrograms/0.5 microliter/side) directly into the VTA of animals with habenular lesions resulted in the performance of stereotyped behaviors that appeared as early as the second MOR exposure and remained at high levels with repeated MOR treatment. The stereotyped behavior shown by lesioned animals did not appear to interfere with the acute locomotor activational effects of intra-VTA MOR nor the development of sensitization to these effects when it was administered repeatedly. These results are in agreement with previous research suggesting that by disinhibiting the dopamine (DA) systems, habenular lesions enhance the acute behavioral activational effects of MOR. The results also suggest that the habenular nuclei do not control the changes in the response of the DA systems underlying the development of sensitization to the locomotor-activating effects of MOR when administered repeatedly. PMID- 1504824 TI - The response of the 5-hydroxyindole oxidation current to noxious stimuli in the spinal cord of anesthetized rats: modification by morphine. AB - The effects of cutaneous noxious heating and of systemic morphine on serotonergic activity in the spinal cord were examined in anesthetized rats. An oxidation current of 5-hydroxyindole signal was seen at 280-300 mV with differential normal pulse voltammetry. Noxious heat stimuli produced a mean signal increase over control values of 15.5 +/- 3.4% at 52 degrees C, and 7.2 +/- 5.5% at 45 degrees C. These increases lasted for 5-10 min. Non-noxious stimuli (37 degrees C) did not affect the 5-hydroxyindole signal. Morphine (0.5, 2.0 and 5.0 mg/kg, i.p.) in the absence of cutaneous stimulation did not change the signal significantly. Systemic morphine alone did not significantly modify the 5-hydroxytryptamine (5 HT) metabolism, as observed in in vivo voltammetry, in the spinal cord of anesthetized rat. However, a low dose of morphine (0.5 mg/kg, i.p.) attenuated the increase in the signal modified by noxious stimuli, and high doses (2.0 or 5.0 mg/kg, i.p.) enhanced it. Both effects of morphine were antagonized by naloxone (0.5 mg/kg, i.v.). It is likely that morphine with noxious stimuli modify the sensitivity of serotonergic descending inhibitory system. It is concluded that noxious heating of the skin increases the 5-HT metabolism in the spinal cord of anesthetized rats and that systemic administration of morphine modulates this 5-HT metabolism. PMID- 1504825 TI - Abnormal profiles of polyunsaturated fatty acids in the brain, liver, kidney and retina of patients with peroxisomal disorders. AB - The polyunsaturated fatty acid (PUFA) composition of the brain was studied in 8 patients with Zellweger's syndrome (ZS), 3 with neonatal adrenoleukodystrophy (NALD), one with bifunctional enzyme deficiency (BED), one with X-linked adrenoleukodystrophy (X-ALD), and one with adrenomyeloneuropathy (AMN). The PUFA composition of the liver, kidney and retina was studied in 8, 6 and 1 patients with ZS, respectively. An infant with NALD and a child with rhizomelic chondrodysplasia punctata (RCDP) were also studied for the PUFA composition of the liver. The liver and kidney of the patient with X-ALD and the liver of the patient with AMN were included in the study. The fatty acid values in the peroxisomal patients were compared with control data obtained in the normal developing brain (38 cases), liver (9 cases), kidney (7 cases) and retina (16 cases). The brain of a patient with metachromatic leukodystrophy (MLD) and the liver of a child with Krabbe's disease (KD) were also studied for comparison. The most constant and severe abnormality in all the peroxisomal patients was a drastic decrease in the total amount of docosahexaenoic acid (22:6 omega 3), especially in the brain. The other product of delta 4-desaturation, 22:5 omega 6, was generally decreased in the brain, liver and kidney of the ZS patients, but very much increased in the brain of two patients with NALD. The 22:6 omega 3/22:4 omega 6 ratio, which remains quite constant throughout normal brain development, was consistently decreased in the peroxisomal brain, in ZS as well as in NALD. This study confirms that, in classical Zellweger's syndrome, the two products of delta 4-desaturation are affected. In contrast, in neonatal adrenoleukodystrophy the deficiency is probably restricted to the omega 3 product of delta 4 desaturation, docosahexaenoic acid, especially in the brain, while the other product, 22:5 omega 6, is either normal or increased, perhaps in an attempt to compensate for the 22:6 omega 3 deficiency in brain membranes. PMID- 1504826 TI - Evidence that long-term estrogen treatment disrupts opioid involvement in the induction of pituitary LH surge. AB - Recent evidence suggests that a decrease in the inhibitory opioid influence is a necessary hypothalamic neural event in the preovulatory and ovarian steroid induced luteinizing hormone (LH) surge. Whether shifts in ovarian steroidal milieu disrupts this neural event is not known. Therefore, the effects of short term (3 days) and long-term (13 or 17 days) estradiol 17 beta (E2) exposure on spontaneous, naloxone (NAL) and progesterone (P)-induced LH surges were assessed in ovariectomized (ovx) rats. Two weeks after ovariectomy, rats received subcutaneous Silastic capsules filled with crystalline E2. In rats exposed to E2 for 3 days and infused with saline intravenously between 11.00-14.00 h, plasma LH rose significantly at 17.00 h. NAL infusion between 11.00-14.00 h in these rats to decrease the inhibitory opioid influence, advanced both the onset of LH rise and amplified the secretion of LH in the afternoon. Continuation of E2 exposure for 13 days produced no deleterious effects on either the spontaneous or NAL induced augmentation in LH responses. However, uninterrupted E2 exposure for 17 days abolished the spontaneous afternoon LH rise and drastically diminished the ability of NAL to advance and amplify the LH response. In the next experiment, we evaluated the effect of P injection (2 mg/rat) at 11.00 h on the afternoon LH release in rats similarly exposed to E2 for either 3 or 17 days. In rats exposed to E2 for 3 days, the P-induced LH release was significantly greater than that observed after saline or NAL infusion.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1504827 TI - Role of glutathione in repair of free radical damage in hippocampus in vitro. AB - Depletion of glutathione (GSH), an intrinsic antioxidant, increases vulnerability to free radical damage in a number of cell systems. This study investigates the role of GSH in limiting electrophysiological damage and/or recovery from free radical exposure in slices of guinea pig hippocampus. Synaptic potentials (PSPs) and population spikes (PSs) were recorded from field CA1. Free radicals were generated from 0.006% peroxide through the Fenton reaction. Analysis of the input output curves showed that peroxide treatment decreased PSPs and impaired ability of the PSPs to generate PSs as previously reported. Recovery was nearly total within a half hour. Treatment with 5 mM buthionine sulfoximine (BSO) for 2 h depleted hippocampal GSH to 79.2% of control values. The extent of free radical damage was not increased. Recovery, however, was only partial. GSH was further depleted by oxidation with diamide or covalent bonding with dimethyl fumarate (DMF) immediately before and during the peroxide treatment. Neither diamide nor DMF treatment in BSO-incubated tissue enhanced peroxide-induced electrophysiological deficits. Following these treatments, however, tissue showed little recovery from free radical damage. We conclude that glutathione is essential for repair processes in hippocampal neurons exposed to oxidative damage. PMID- 1504829 TI - Behavior of axons, Schwann cells and perineurial cells in nerve regeneration within transplanted nerve grafts: effects of anti-laminin and anti-fibronectin antisera. AB - Wistar rats (close cloned strain) were used to investigate the effect of endogenous laminin and fibronectin on axons, Schwann cells and perineurial cells in the regenerating peripheral nervous system (PNS). Sciatic nerve grafts obtained from donor rats were frozen, thawed and treated with rabbit anti-rat laminin or anti-fibronectin antiserum. Control grafts were treated with normal rabbit serum alone. One cm long portions of the sciatic nerve of the recipient rats were replaced with grafts. At 15 days after transplantation the number of regenerated axons in the laminin- and fibronectin-depleted grafts was half of that in the control. The growing axons in the laminin-depleted grafts did not recognize the basal lamina scaffolds (BLS) remaining in the basal lamina tubes, while in the control and fibronectin-depleted grafts 90% or more of axons grew inside the BLS. Elongation of axons always preceded migration of Schwann cells with the latter subsequently adhering to and wrapping around the former. Perineurium-forming fibroblastic cells recognized the combination of axons and Schwann cells and formed perineurial fasciculi around them. These fibroblastic cells did not recognize empty BLS but responded to them only when fibronectin was depleted. Macrophages sometimes closely faced the naked axons which elongated outside the BLS. These results suggest that in the early stages of nerve regeneration endogenous laminin and fibronectin not only regulate the growth of regenerating nerve fibers, but also exert a positive influence on perineurial cells and macrophages, both of which play important roles in nerve tissue injury and repair. PMID- 1504828 TI - Fos expression in intrastriatal striatal grafts: regulation by host dopaminergic afferents. AB - Previous studies have shown that transplants of fetal striatum, implanted into the ibotenic acid-lesioned striatum of adult rats, become innervated from the host nigrostriatal dopamine (DA) pathway. In the present study we have used DA receptor-mediated expression of the Fos protein (i.e. the product of the immediate-early c-fos gene) as a cellular marker for functional dopaminergic host graft interactions in the striatal grafts. Amphetamine (5 mg/kg; 2 h) induced Fos like immunoreactivity in clusters of cells located mainly within the DARPP-32 positive areas within the transplants, i.e. within the striatum-like graft compartment which is preferentially innervated by the host DA afferents. As in the normal striatum, this effect was largely, although not completely, abolished by a 6-hydroxydopamine lesion of the ipsilateral nigrostriatal DA pathway. Apomorphine (0.25 mg/kg; 2 h) had no detectable effect in grafts with an intact host DA system. Two to 3 weeks after a 6-OHDA lesion of the host DA pathway (i.e. a time sufficient for DA receptor supersensitivity to develop), apomorphine induced extensive Fos-activation selectively within the DARPP-32-positive areas of the graft. The magnitude of the response was similar to that seen in the DA denervated host striatum. Dual Fos/DARPP-32 immunostaining revealed that the activated graft neurons were, at least in part, DARPP-32-positive. In intrastriatal grafts of fetal neocortical tissue, which were studied for comparison, the amphetamine- and apomorphine-induced effects on Fos expression were much smaller and similar to that seen in the DARPP-32-negative, non-striatal compartment within the striatal grafts.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1504830 TI - Testosterone reverses a senescent decline in extrahypothalamic vasopressin mRNA. AB - The biosynthetic activity of extra-hypothalamic vasopressin (VP) neurons in the bed nucleus of the stria terminalis (BNST) is regulated by gonadal steroids. These neurons have also been implicated in a number of behaviors that are impaired in aging. We previously reported that VP mRNA labelling in the BNST is decreased in senescent rats. We hypothesized that the age-related decrease in VP mRNA labelling is due to the decline in circulating testosterone (T) levels in aged animals. T or saline was administered peripherally for 1 month in physiologic or superphysiologic doses to 3 month old or 24 month old Fischer 344 male rats. In situ hybridization and quantitative autoradiography for VP mRNA in the BNST were performed using a 48-base 35S-labelled oligonucleotide probe. Administration of T completely reversed the decline in VP mRNA labelling in the aged animals. Superphysiologic T further increased VP gene expression in both age groups. These data are consistent with a previous report of T-induced increase in VP immunoreactive fiber density in other extrahypothalamic regions of the brain in aged rats. This study offers further evidence that alterations in the hormonal milieu may play an important role in modulating neuronal biosynthetic activity in senescence. PMID- 1504831 TI - Auto- and cross-correlation analysis of subthalamic nucleus neuronal activity in neostriatal- and globus pallidal-lesioned rats. AB - Statistical analyses (autocorrelation and first-order interstimulus interval) were conducted on the spontaneous activity of over 420 subthalamic neurons recorded in 5 groups (control, large globus pallidus kainic acid lesion, partial globus pallidus kainic acid lesion, partial globus pallidus ibotenic acid lesion and neostriatal lesion) of anesthetized rats. Cross-correlation and peristimulus time histogram (to frontal motor cortex stimulation at 0.7 mA) analyses were conducted on pairs (n = 58) of subthalamic neurons recorded simultaneously on a single microelectrode. Lesion of the globus pallidus increased spontaneous firing rate as compared to controls and shifted the pattern of spontaneous activity from either a regular or irregular pattern to a markedly bursting pattern. Neostriatal lesion reduced firing rate and reduced the likelihood of highly regular firing. In control, neostriatal and partial lesioned animals, approximately 1 in 3 pairs of neurons showed correlated firing. The correlations were joint increased probabilities of firing over intervals of 200-400 ms, suggesting a shared excitatory input. No short-interval (less than 10 ms) correlations were seen. Large globus pallidus lesion increased the likelihood of correlated firing (12 of 16 pairs). In all groups of animals the peristimulus time histograms (PSTHs) to motor cortex stimulation were more similar than would be expected by chance and pairs of neurons showed the same increases in response following globus pallidus lesion. Thus adjacent neurons share common cortical inputs and responsiveness to those inputs. These changes indicate that the globus pallidus influences the spontaneous firing rate and pattern of subthalamic neurons as well as the degree of correlated firing of adjacent neurons. PMID- 1504832 TI - Biochemical characterization of independent olfactory receptor sites for 5'-AMP and taurine in the spiny lobster. AB - To understand the initial events in chemosensory transduction (i.e. binding of odorants to olfactory receptor sites), we have utilized a radioligand-receptor binding assay on a tissue preparation that is enriched in dendritic membrane from olfactory receptor cells in the spiny lobster Panulirus argus. Radioligands used were tritiated adenosine 5'-monophosphate (AMP) and taurine, which are two of the most excitatory compounds for spiny lobsters. Our results indicate the existence of two independent types of binding sites--a taurine binding site and an AMP binding site. For both the taurine and AMP binding sites, odorant binding is rapid, reversible, and saturable. KD values for the taurine and AMP binding sites are 2.3 and 2.0 microM, respectively, and Bmax values are 159 and 3.2 fmol/micrograms protein, respectively. The fact that the specificity, affinity, and independence of these two binding sites as defined in these biochemical studies are in agreement with those from electrophysiological studies suggests that these binding sites are olfactory receptor sites involved in sensory transduction. PMID- 1504834 TI - Ultrastructural immunolocalization of rat oxytocin-neurophysin in transgenic mice expressing the rat oxytocin gene. AB - Cell-specific expression of the rat oxytocin (OT)-neurophysin transgene in mice was achieved using a construct containing both OT and vasopressin genes (Young III, W.S., Reynolds, K., Shepard, E.A., Gainer, H. and Castel, M., Cell-specific expression of the rat oxytocin gene in transgenic mice, J. Neuroendocrinol., 2 (1990) 1-9). The present study describes the distribution of the protein products of these genes in various regions of the cell, and determines whether the transgenic rat and endogenous mouse OT-neurophysins are colocalized within the same neurosecretory granules. Two monoclonal antibodies against OT-neurophysins were used: PS38 which can react with both rat and mouse OT-neurophysin (pan specific), and PS67 which is specific for rat OT-neurophysin only. Various approaches to double immunolabeling at the ultrastructural level were employed; these included: (1) pre-embedding immunoperoxidase followed by post-embedding immunogold; (2) post-embedding immunolabeling using gold particles of different sizes; and (3) labeling of consecutive ultrathin sections with different antibodies. Results from each of these approaches showed that both in the transgenic mouse and in the rat (used as control), immunocytochemical labeling for both PS38 and PS67 occurred in the same OT-ergic neurosecretory granules. In the control mouse, only PS38 elicited labeling. Hence, it may be concluded that the protein and peptide products of the transgene and the endogenous gene for OT neurophysin are being processed similarly in the cell and finally concentrated together in the same neurosecretory granules. PMID- 1504833 TI - Symmetric synapses formed by callosal afferents in rat visual cortex. AB - Following an electron microscopic examination of 437 degenerating terminals of callosally projecting axons in layer II/III at the 17/18a border, it has been found that some of these terminals form symmetric synapses with dendritic shafts (1.83%), pyramidal cell bodies (1.37%) and dendritic spines (0.46%). The remainder of the axon terminals (96.33%) form asymmetric synapses, mainly with dendritic spines although a few form synapses with dendrites. These results suggest that in the rat visual cortex the corpus callosum is a source of both inhibitory and excitatory input to the contralateral hemisphere. PMID- 1504835 TI - Further studies on interactions between periaqueductal gray, nucleus accumbens and habenula in antinociception. AB - Previous findings from this laboratory with the intracerebral microinjection technique suggested that the periaqueductal gray (PAG), nucleus accumbens, and habenula might constitute a unidirectional loop to play their roles in pain modulation. In the present study we demonstrate that intra-habenular injection of naloxone antagonizes the analgesia elicited by morphine injected into the periaqueductal gray (PAG) and that intra-accumbens injection of naloxone is capable of attenuating the analgesic effects of morphine injected into the habenula. These results indicate that the relationships between these nuclei may be more complex than the putative unidirectional loop. PMID- 1504836 TI - TNF alpha induces IL-6 production by astrocytes but not by microglia. AB - Astrocytes and microglia, both produced interleukin-6 (IL-6) in culture by lipopolysaccharide (LPS) stimulation. IL-6 activity was detected 3-5 h after LPS stimulation and reached a maximum at 10 h. Microglia responded faster than astrocytes. Tumor necrosis factor alpha and interleukin 1 also induced IL-6 mRNA and biological activity in astrocytes, but not in microglia. Among these stimuli, LPS was the most potent inducer of IL-6 production by astrocytes. Our results suggest that different regulatory mechanisms for cytokine production exist in glial cells. The possible roles of astrocytes and microglia in CNS immune responses are also discussed. PMID- 1504837 TI - Neurochemical effects of vagus nerve stimulation in humans. AB - An implanted stimulating device chronically stimulated the left cervical vagus nerve in epileptic patients. Cerebrospinal fluid concentrations of free and total gamma-aminobutyric acid, homovanillic acid, 5-hydroxyindoleacetic acid, aspartate, glutamate, asparagine, serine, glutamine, glycine, phosphoethanolamine, taurine, alanine, tyrosine, ethanolamine, valine, phenylalanine, isoleucine, vasoactive intestinal peptide, beta-endorphin, and somatostatin were measured before and after 2 months of chronic stimulation in six patients. Significant increases were seen in homovanillic acid and 5 hydroxyindoleacetic acid in three patients, and significant decreases in aspartate were seen in five patients. These changes were associated with a decrease in seizure frequency. PMID- 1504838 TI - Effect of age on [3H]nisoxetine binding to uptake sites for norepinephrine in the locus coeruleus of humans. AB - [3H]Nisoxetine ([3H]NIS) was used to measure uptake sites for norepinephrine (NE) in the locus coeruleus (LC) of humans. Regression analysis demonstrated an inverse correlation between age and the binding of [3H]NIS to NE uptake sites in the LC (r = -0.6; P less than 0.01). Since considerable cell loss has been reported to occur with age in the human LC, the decreased binding of [3H]NIS probably reflects loss of LC cells rather than a down-regulation of these sites. PMID- 1504839 TI - Olfactory bulb output neurons excited from a basal forebrain magnocellular nucleus. AB - We present intracellular data which demonstrates a unique facilitatory centrifugal influence on the output cells of the olfactory bulb; the source being the lateral component of the nucleus of the horizontal limb of the diagonal band (HDB), part of the basal forebrain magnocellular complex. Damage to this facilitatory HDB influence may explain the loss of olfactory sensitivity seen early in Alzheimer's disease in which pathological changes occur in the basal forebrain. PMID- 1504840 TI - Involvement of hypothalamic noradrenergic systems in the modulation of intestinal motility in rats. AB - Selective lesions of the noradrenergic systems of the paraventricular nucleus (PVN) of the hypothalamus with 6-hydroxydopamine (6-OHDA) lengthen the periodicity of the migrating myoelectric complex (MMC), an index of intestinal motility, in rats. These lengthening effects resemble those obtained after lesions of the locus coeruleus (LC), thus suggesting that noradrenergic terminals from LC to the PVN are involved in this modulation. PMID- 1504841 TI - A double-label study demonstrating that all serotonin-like immunoreactive amacrine cells in the larval tiger salamander retina express GABA-like immunoreactivity. AB - A previous study localized serotonin-like immunoreactivity to amacrine cell populations in the larval tiger salamander retina. The present double-label immunocytochemical analysis of the tiger salamander retina was performed to determine if gamma-aminobutyric acid (GABA)-like immunoreactivity is expressed by serotonin-immunoreactive amacrine cells. More than 3,000 serotonin-amacrine cells were observed in double-label preparations, and all were found to express GABA like immunoreactivity. This finding extends previous studies of serotonin-GABA coexistence in the retina by providing the first report of the co-localization of endogenous serotonin and GABA-like compounds in a retinal neuron. PMID- 1504842 TI - Identification of an AII(3-8) [AIV] binding site in guinea pig hippocampus. AB - A unique angiotensin binding site specific for the hexapeptide, AII(3-8), has been identified in guinea pig hippocampus. This binding site, which is present in the pyramidal cell layer of CA1, CA2, CA3 of the hippocampus and dentate gyrus, binds AII(3-8) with high affinity (KD = 1.29 +/- 0.18 nM) in a saturable manner (Bmax = 449 +/- 62 fmol/mg protein). The N-terminal structure of the binding ligand is paramount in determining the binding affinity. The C-terminal requirements seem less stringent as evidenced by the binding affinity of AII(3-7) (KD = 20.9 +/- 2.1 nM). Neither AII, AIII,Sar1, Ile8-AII, Dup 753 nor CGP42112A appear to bind, indicating that this binding site is neither the AT1 nor AT2 sites described for AII/AIII. Autoradiographic analysis of hippocampus binding confirms the inability of Sar1,Ile8-AII to compete for [125I]AII(3-8) binding. Conversely AII(3-8) was unable to displace [125I]Sar1,Ile8-AII binding. PMID- 1504843 TI - The magnocellular arginine-vasopressin mRNA responds differently to food deprivation between the supraoptic and paraventricular nuclei of the hypothalamus in adrenalectomized rats with low corticosterone replacement. AB - We previously reported that food deprivation significantly decreased arginine vasopressin (AVP) mRNA levels in the supraoptic (SON) and paraventricular (PVN) nuclei of the hypothalamus and also greatly stimulated the pituitary adrenocortical system in rats. In this study, we deprived adrenalectomized rats with subcutaneously implanted low-dose corticosterone pellets (ADX + B) of food for 3 days to investigate the involvement of corticosteroid feedback regulation in the food deprivation-induced decrease in AVP mRNA in both the SON and the PVN. The plasma corticosterone levels in these animals were maintained at low levels constantly over 24 h. The ACTH concentration in the morning plasma was markedly increased in the food-deprived ADX + B rats as compared to the fed ADX + B rats. Food deprivation significantly decreased the corticotropin-releasing hormone (CRH) content in the median eminence and increased the CRH and AVP content in the neurointermediate lobe of the pituitary. Semiquantitative in situ hybridization histochemistry revealed that AVP mRNA levels were decreased in the SON but, inversely, increased in magnocellular as well as parvocellular subdivisions of the PVN following food deprivation. These results suggest that: (1) AVP mRNA responds differently to food deprivation between the SON and the PVN; (2) the glucocorticoid feedback can exert on AVP mRNA in the PVN but not in the SON in the food-deprived rats; and (3) food deprivation affects the neurohypophysial levels of CRH and AVP. PMID- 1504845 TI - Frequency selectivity is related to temporal processing in parallel thalamocortical auditory pathways. AB - Lemniscal and non-lemniscal parallel thalamocortical auditory pathways have been identified with the ventral medial geniculate body (MGB) vs. the dorsal and medial MGB, respectively. Lemniscal neurons have narrow frequency tuning and provide highly specific frequency information to the auditory cortex whereas non lemniscal neurons generally have broader tuning and greater response lability, including plasticity of frequency receptive fields during learning. To determine if frequency selectivity is related to temporal fidelity of response, we measured both the breadth of tuning and neuronal excitability in a paired tone paradigm for single neurons throughout the MGB. Excitability to the second tone of a pair was directly correlated with frequency selectivity: the narrower the frequency tuning, the greater the excitability. Cells with broad tuning based on multiple peak response areas also were less excitable than cells with single-peak RAs. Cells in the ventral MGB showed greater temporal fidelity of response (greater excitability) than cells in the dorsal and medial MGB. These findings show that high degrees of both frequency selectivity and temporal response fidelity are characteristic of the lemniscal, but not the non-lemniscal, thalamocortical auditory system. PMID- 1504844 TI - Effects of inorganic constituents of saliva on taste responses of the rat chorda tympani nerve. AB - The effects of saliva on the taste responses of the chorda tympani nerve to the 4 standard chemical stimuli (sucrose, NaCl, HCl, and quinine hydrochloride) and water were investigated in anesthetized rats. When the tongue was adapted to pilocarpine-stimulated whole saliva (pH 8.7), the magnitude of neural response to sucrose was about 2 times that obtained when the tongue was adapted to distilled water. Under saliva-adapted conditions, the magnitude of responses to other taste stimuli was reduced by 10-30%, and the water response appeared. These changes were dependent on the concentration of electrolytes (Na+, K+, Cl-, and HCO3-) and on the pH of the saliva. When the tongue was adapted to 10-30 mM NaHCO3 (pH 8.4 8.6), taste and water responses were similar to those under saliva-adapted conditions. Single fiber analyses revealed that the enhancement of the sucrose response after adaptation to NaHCO3 was produced by an increased overall activity of sucrose-responsive fibers. The correlation coefficients of the magnitude of the taste responses between the 4 taste stimuli remained unchanged, but the water response showed a high correlation to HCl and quinine hydrochloride responses after adaptation. Possible mechanisms for the effects of saliva on taste and water responses were discussed. PMID- 1504846 TI - Hippocampal cholinergic alterations and related behavioral deficits after early exposure to phenobarbital. AB - Mice were exposed to phenobarbital (PhB) prenatally and neonatally. Prenatal exposure was accomplished by feeding the mother PhB (3 g/kg milled food) on gestation days 9-18. Neonatal exposure was accomplished by daily injections of 50 mg/kg sodium PhB directly to the pups on days 2-21. Long-term biochemical alterations in the pre- and postsynaptic septohippocampal system, as well as related behavioral deficits, were assessed in the treated animals. Significant increase in B(max) values for binding of [3H]QNB to muscarinic cholinergic receptors was obtained on both ages 22 and 50 in prenatally (40-90%, respectively, p less than 0.001) and neonatally exposed (58-89%, p less than 0.001) mice whereas Kd remained normal. Similarly, a significant increase of inositol phosphate (IP) formation in response to carbachol was found after both prenatal and neonatal exposure to PhB (p less than 0.05). No alterations in choline acetyltransferase (ChAT) activity were observed in the prenatally or neonatally treated animals. The early exposed mice showed deficits in the performance in Morris water maze, a behavior related to the septohippocampal pathway. The results suggest that early exposure to PhB induces alterations in postsynaptic components of the hippocampal cholinergic system and concomitantly to impairment in hippocampus-related behavior. PMID- 1504847 TI - Neural circuit computation: complex patterns in the olfactory bulb. AB - The olfactory bulb principal neurons show complex responses during olfactory stimulation that are characterized by periods of profound suppression, temporal patterns of activity, and nonmonotonic intensity response functions. The model presented here suggests that these features may arise from changing spatial patterns of activity across the bulbar surface due to restricted (chemotopic) activation in bulbar glomeruli. The model is based on a simplified version of the bulbar neural circuit as it is presently known from anatomical and physiological investigations and provides explanations for several anomalous bulbar response patterns. PMID- 1504848 TI - Facilitation of sexual behavior shortly after electrolytic lesion of the medial preoptic area: what does it mean? AB - To analyze the behavioral effects of an unphysiological manipulation of the medial preoptic area (MPOA), sexually experienced male rats received small bilateral electrolytic lesions within this area. Thirty-five percent of the lesioned animals showed a drastic facilitation of sexual behavior when tested 3 h after lesion. The number of intromissions, ejaculation latency, and postejaculatory interval were drastically reduced. The mean number of ejaculations was significantly higher in lesioned animals that displayed the behavior in comparison both to an intact group and a sham-lesioned group. Neither the size of the lesion nor its exact location could be correlated with the facilitation of sexual behavior. However, animals that showed facilitation tended to have the lesion located in the ventral part of the MPOA. Lesions rostral or dorsal to the MPOA were ineffective. It is suggested that the small electrolytic lesions in the MPOA produced iron deposits that stimulated the remaining intact preoptic region, resulting in the drastic facilitation of sexual behavior. The results of the present study support the hypothesis suggesting that the MPOA is involved in the mechanisms related to the initiation and execution of sexual behavior. PMID- 1504849 TI - Coexistence of autonomic and somatic mechanisms in the pressor areas of medulla in cats. AB - The effects of electrical stimulation and microinjection of sodium glutamate (0.5 M) in the sympathetic pressor areas of the dorsal medulla (DM), ventrolateral medulla (VLM), and parvocellular nucleus (PVC) on the knee jerk, crossed extension, and evoked potential of the L5 ventral root produced by intermittent electrical stimulation were studied in 98 adult cats anesthetized with chloralose and urethane. During electrical and glutamate stimulation of these pressor areas, in addition to the rise of systemic arterial blood pressure marked inhibition of the spinal reflex was produced, indicating presence of neuronal perikarya responsible for these actions. Mild to moderate augmentation of spinal reflexes was also observed during brain stimulation but only in a few cases. The magnitude of the somatic effects among the pressor areas of the VLM, DM, and PVC subsequent to glutamate activation was about the same. Induced spinal reflex inhibition, independent from the baroreceptor and vagal influence, remained essentially unaltered after acute midcollicular decerebration. The inhibition was also observed in cats decerebellated 8-10 days in advance. The inhibition was not affected after bilateral electrolytic- or kainic-acid-induced lesions in the paramedian reticular nucleus (PRN). On the contrary, PRN-induced spinal reflex inhibition was attenuated after bilateral lesions in the DM or VLM. Data suggest that there coexists neuronal subpopulations in the VLM, DM, and PVC that can affect both the sympathetic pressor systems and spinal reflexes. PMID- 1504851 TI - Elevated content and secretion of gut GLI in VMH-lesioned rats. AB - Gut glucagon-like immunoreactivity (GLI), a supposed intestinal growth factor in the plasma and gastrointestinal tract, and weight of the gastrointestinal tract, an intestinal growth indicator, were examined in ventromedial hypothalamic (VMH) lesioned rats 1 week after VMH lesions. Postprandial plasma gut GLI in VMH lesioned rats was significantly higher than that in control rats. The content of gut GLI in all gastrointestinal sections except the duodenum in VMH-lesioned rats was significantly greater than that in control rats. Gel chromatography in the lower portion of the small intestine in which GLI content was the highest of all sections revealed the same pattern in both VMH-lesioned and control rats with two peaks of similar molecular size. Weight of all gastrointestinal sections except the cecum in VMH-lesioned rats significantly increased. These results demonstrated that both gut GLI secretion and production were enhanced in VMH lesioned rats. The elevated gut GLI release may accelerate growth of the gastrointestinal tract in these animals. PMID- 1504850 TI - Hypothalamic neuronal responses to interleukin-6 in tissue slices: effects of indomethacin and naloxone. AB - We recently reported that human recombinant interleukin-6 (hrIL-6) microinjected into the preoptic area (POA) of guinea pigs induced fever at high doses, suggesting that IL-6 may be another endogenous pyrogen. This study was undertaken to determine whether hrIL-6 affects the single-unit activity of thermosensitive and thermally insensitive neurons in hypothalamic tissue slices and whether indomethacin (Indo) or naloxone (Nal), a cyclooxygenase inhibitor and a mu-opioid receptor antagonist, respectively, influences the effects of hrIL-6 on those neurons. hrIL-6 (2 x 10(3)-8 x 10(3) U/ml) depressed the activity in 50 (83%) of 60 warm-sensitive (W) neurons and excited all 4 cold-sensitive (C) neurons found. It had no effect, however, on 14 (48%) of 29 thermally insensitive (I) neurons, albeit 7 and 8 I neurons decreased and increased their firing rates, respectively. Indo (0.05-1 mg/ml) blocked the effect of hrIL-6 on 22 of 24 W neurons and 2 C neurons tested. Nal(0.1-1 mg/ml) blocked or reduced the effect of hrIL-6 on 21 of 25 W neurons and 1 C neuron recorded. These drugs induced no neuronal response per se. Nal at 2-5 mg/ml, which increased the activity of four W neurons by itself, reversed their depressed response to hrIL-6. These results support the possibility that IL-6-induced fevers may be mediated through an effect on thermosensitive neurons in the POA and that opioids and prostaglandin E may both be involved in this process. PMID- 1504852 TI - Airflow receptors in the lip and buccal mucosa. AB - Airflow receptor afferents in the oral mucosa responding to changes in intraoral air pressure during blowing were found to be innervated by the infraorbital nerve. They provided one response corresponding to the onset of blowing, a second related to an increase in air pressure, a third corresponding to the cessation of blowing, and a fourth that exhibited little change throughout sustained blowing. Intraoral air pressure in the cavity between the lips and the velopharyngeal portal may be monitored by these receptors, and the data they provide may contribute to the control of phonation. PMID- 1504853 TI - Intracerebroventricular LHRH relieves behavioral deficits due to vomeronasal organ removal. AB - Contact between the sexes in many species is known to produce hormonal changes in the male [increases in serum luteinizing hormone (LH) and/or testosterone] that can be interpreted as due to an intracerebral release of LH-releasing hormone (LHRH). In some circumstances, these hormonal changes appear to depend on an intact vomeronasal sensory system. Exogenous LHRH is also known to facilitate mating behavior in several species. We show here that LHRH delivered into the cerebral ventricles can restore some mating behavior lost when the vomeronasal organs are removed from sexually inexperienced male hamsters. The results are consistent with our working hypothesis that intracerebral LHRH release is an intermediate in the facilitation of mating behavior by vomeronasal sensory input. PMID- 1504854 TI - Implantation of genetically modified mesencephalic fetal cells into the rat striatum. AB - Transplantation of dopamine (DA) cells into the rat model of hemiparkinsonism induced by intranigral 6-hydroxydopamine (6-OHDA) injections has so far focused mainly on DA replacement via a pump-like mechanism. In the present study, we employed a model of hemiparkinsonism that uses an intrastriatal approach to lesioning the nigrostriatal DA pathway to assess the possibility of using cell transplantation to cause regeneration of that system. Toward that end, we transplanted two types of cells on the side of the 6-OHDA-induced lesions: 1) nonmodified fetal mesencephalic cells and 2) fetal mesencephalic cells that have been infected with a retrovirus vector containing a PKC beta 1 cDNA. Both types of cells cause behavioral improvement although the changes were more prominent and occurred earlier in the PKC-modified groups. Tyrosine hydroxylase (TH) immunocytochemistry revealed significantly cell survival in both groups of animals; in situ hybridization studies confirmed the continuous expression of TH mRNA in both groups. Interestingly, long TH-positive axons were observed only in the striata of animals implanted with PKC-modified cells. More importantly, surviving endogenous nigral TH-positive cell bodies were found only on the lesioned side in the latter group. The observations in these animals were associated with significantly smaller decreases in [3H]mazindol-labeled DA uptake sites in both the striata and substantia nigra pars compacta on the side ipsilateral to the 6-OHDA-induced lesions. Furthermore, immunohistochemical studies revealed increased gliosis in the striata of animals grafted with the PKC modified cells. When taken together, these results indicate that transplantation of normal fetal mesencephalic cells can cause behavioral improvement by providing DA to the host striata whereas PKC-modified cells can, in addition, prevent the progressive degeneration of or cause regeneration of the dying nigrostriatal DA neurons in this model of hemiparkinsonism. These results are discussed in terms of their support for a role for second messenger systems and glial cells, as well as extracellular matrix molecules in the regeneration of the CNS. PMID- 1504855 TI - Subnuclear organization of the human caudal nucleus of the solitary tract. AB - The caudal human nucleus of the solitary tract (NTS) is composed of 10 subnuclei. The commissural subnucleus spans the midline below the obex, merging rostrally into the medial subnucleus. The other subnuclei of the NTS are best seen just above the obex. The ventrolateral subnucleus contains large, darkly staining neurons. The interstitial subnucleus consists of neurons lying in groups intermingled with the fibers of the tract. The lateral subnucleus is small at caudal levels, merging with the interstitial subnucleus more rostrally. The dorsal subnucleus contains large melanotic neurons and encircles the substantia gelatinosus, a round, cell-poor subnucleus. The ventromedial subnucleus curls around the medial and ventral edge of the tract. The intermediate subnucleus, laying ventrolateral to the dorsal motor nucleus of the vagus, also contains melanotic neurons. The subpostremal subnucleus separates the area postrema from the NTS proper. The medial subnucleus is the largest subnucleus in the caudal NTS, containing medium-sized fusiform neurons. Adoption of a uniform cytoarchitectural map of the caudal NTS will permit more accurate comparisons between human and nonhuman studies. PMID- 1504856 TI - [Rupture of abdominal aorta aneurysms. Study of 92 cases operated on over a ten year period (1980-1989)]. AB - From January 1980 to December 1989, 92 ruptured abdominal aortic aneurysms (AAA) were operated upon in emergency at our institution. During the same period, 747 AAA were operated in election or in the absence of rupture. The mean age of patients was 72.8 +/- 9.1 (52-95). There were 81 men and 11 women. Etiology of the AAA was common degenerative in all cases except in one case of aortic dissection and one case of infectious aneurysm. 27 (29.3%) patients presented antecedents of bronchopathy, 31 (33.7%) antecedents of hypertension and 36 (39.1%) antecedents of coronary heart disease. All patients were operated upon under general anesthesia, in two (2.1%) cases through a thoraco-abdominal exposure, in one case through a lombotomy, in one case, using exclusion and an extra anatomic bypass and through a midline transperitoneal laparotomy in all 88 (96.9%) other cases. The mean diameter of the AAA was 9 +/- 3.9 (4-25) cm. The rupture was intra-peritoneal in 26 (28.3%) cases, intra caval in 5 (5.4%) cases, intra duodenal in 2 (2.2%) cases and retro peritoneal in all the other 59 (64.1%) cases. The aorta was cross clamped above the renal arteries in 15 (16.3%) cases, under the renal arteries in 48 (52.2%) cases and at both levels in 29 (31.5%) cases. Surgical treatment consisted in an aorto-aortic tubular graft in 45 (48.9%) cases, a bifurcated aortic graft in 32 (34.8%) cases, an exclusion with extra anatomic bypass in one (1%) case and could not be completed before the death of the patient in 14 (15.3%) cases. There were 56 (60.9%) deaths, 27 (29.4%) in the per operative and 29 (31.5%) in the post operative periods after a mean time of 5.7 +/- 9.2 (0-36) days. The cause of the death was hemorrhage in 25 (44.4) cases, cardiac complications in 28 (50%) cases, renal insufficiency in 1 (2%) case, pulmonary complications in 1 (2%) case and septic complications in one (2%) case. During the period of the present study, rupture of an AAA remained, in our institution as in other institutions an often fatal condition. This condition could probably be avoided with a policy of early detection and surgical treatment. PMID- 1504857 TI - [Human placental implantation]. AB - Like malignant tumor cells, cells of the trophoblast, of the blastocyst and of the hemochorial placenta are highly invasive. This invasiveness is essential for implantation and penetration of the epithelial and connective tissues of the endometrium. According to Hertig's data and the observations (henceforth classical) of the Carnegie Foundation, it is commonly admitted that trophoblastic cells penetrate rapidly the blood vessels of the maternal endometrium, open them and allow the establishment of a communication between maternal circulation and fetal tissues from the 20th day after fertilization. As suggested in the classical textbooks of Embryology, the hemochorial placentation would be established very early in human pregnancy. These observations (essentially histological) are actually contradicted by clinical observations performed by Doppler contact echography and by dynamic observations with a microvideo camera implanted in the intervillous placental chamber. Echographic observations coupled with the study of Doppler signals suggest the absence of placental maternal vascularization during the first trimester of pregnancy. It is possible to mount an optical system between the membranes and the uterine wall up to the placental tissue to observe the placental circulation. This direct observation concludes to the absence of maternal vascularization in the intervillous chamber during the first trimester of pregnancy. At the beginning of the 13th week of gestation, uterine arteries open directly into the intervillous chamber ensuring the direct perfusion of placental villi. These informations allow to suggest that the placenta becomes hemochorial at the beginning of the second trimester of pregnancy. PMID- 1504858 TI - [Coronary disease in black Africans: epidemiology, risk factors, clinical symptomatology and coronarography, evolution]. AB - The study of the epidemiological data (published since 1952) seems to show an increasing frequency of the coronary disease for 15 last years. But this incidence seems to reach a stable level about 6 to 7% of the cardiovascular diseases at the Abidjan Institute of Cardiology; and 3.17% in a study in 13 countries but without coronarography (except at the Abidjan Institute). The study of the risk factors show that they are the same ones than in Europa. The risk index in Black Africa was 2.1 to 2.7 risk factor patient. These numbers are lesser than the risk index noted in France (3.6 in coronary patients and 1.9 in non-coronary subjects). The signs of the disease show that myocardial infarctions were frequent (48.8%) and often were the first manifestations of the coronary disease (40%). Angina pectoris was observed in 32.2%, an ischemic cardiomyopathy in 6.6% and a ventricular aneurysm in 6.6%. A silent ischemia was observed in 5.5% among at risk diabetic patients. The in-hospital mortality after myocardial infarction was 15% and was the same in European and African patients. But the mortality in Africans was greater than in Europeans the next years. Coronarography showed that 18.8% of the patients with coronary disease had normal coronary arteries. The arteries were also normal in 19.9% of the patients examined after an infarction. These high percentages can be related to coronary arterial spasms or to recanalized thrombosis. A spontaneous spasm was observed in 6.6% of the patients (a provoked coronary arterial spasm was not studied. The coronary arterial lesion was an one artery disease in 38.8% of the coronary patients and 50% of the patients with infarction. The stenosis were frequently proximal (82.6%) and the anterior descending artery was interested in 45.6%. Ventricular aneurysms were observed in 56.6% and the ejection fraction was lower than 0.50 in 63.3%. These data permit to compare the myocardial infarction of Blacks with the myocardial infarction of the young occidental men. We can think that thrombolysis or angioplasty would be very useful but they are often impossible in the Black African conditions. PMID- 1504859 TI - [Intraluminal transport of vitamin B12]. AB - Since the existence of vitamin B12 was suggested by Castle in the first few decades of this century, vitamin B12 has been the subject of many studies which have proved the high complexity of it assimilation by the organism. Over the last few years the marked progress in functional digestive exploration methods and the physical and the chemical characteristics of biological molecules have revived the established idea of the vitamin's intraluminal transit. Our recent studies have been concentrated on the bilioduodenopancreatic stage of the vitamin B12 transport. In nature, vitamin B12 is only exceptionally met in its free form it is always associated with a binder. Like a ball being tossed from one player to another, it moves between binders. Alimentary vitamin B12 released from its protein complexes by culinary preparation and gastric secretions, is combined with haptocorrin. Around the duodenum the transfer of B12 on intrinsic factor is due to partial degradation of haptocorrin by pancreatic enzymes and intraluminal pH balance. This combined with intrinsic factor the vitamin can be caught by the ileal receptor. The partial degradation haptocorrin joins vitamin B12 analogs from excreted bile or synthesized by the intestinal microorganisms. PMID- 1504860 TI - [Analytic study of noise]. AB - This analysis examines the definition, origin, category, acoustic and psycho acoustic properties and the quantitative and qualitative measurements of noise, allowing one to delineate the problems associated with such a disturbance. There are several definitions of sound, depending on the angle at which one considers the phenomenon: social, acoustic, psycho-acoustic or medical. The acoustic aspect determines its physical characteristics; the psycho-acoustic aspect deals specifically with its effect on the human ear. Noise assumes very different aspects: ambient, stable, fluctuating, intermittent, pulsing. It presents a disturbance depending on different factors: intensity, frequency, length of exposure, mode of arrival, evolution in time, acoustic characteristics. Over and above all these is added a factor of personal sensitivity, varying from one individual to another. Measurement of noise is performed with the help of an instrument called a sonometer, which records the level of the acoustic pressure, i.e. intensity. From this point, one can evaluate the magnitude of auditive disturbance, Leq. Measurement of human hearing has also been established. This is called audiometry. It allows one to assess the auditive value by drawing a graph: the audiogram. AFNOR has established a classification of noises to be found related to social life. Two broad categories: indoor noises, related to the activity in an apartment building and within the lives of its inhabitants, and outdoor noises, linked to traffic noise and its different forms, and to economic and social activity and noise produced by recreational pursuits. PMID- 1504861 TI - [Noise and hearing]. AB - The injuries induced by noise to auditory system affect above all the inner ear. Thus the hair cells forming the most fragile structures of the sensorial neuro epithelium will suffer from hair disturbances. As a result these lesions will reduce hearing acuity and sensitivity leading to noise induced hearing loss. There are two types of hearing loss. The sudden hearing loss, called acute sonorous trauma, or the insidious one due to industrial-like noises. On the other hand, noisy environments may have some effects on the intelligibility known as effects on the recognition of speech. To conclude, the epidemiological studies carried on all sections of the population, including teen-agers, revealed a worrying yielding of their hearing performances, probably resulting from excessive level of noisy surroundings as supposed some years ago by Glorig. PMID- 1504862 TI - [Non-auditory responses to noise. Objective estimation. Experimental and individual analyses]. AB - The physiological reactions to a strong noise are immediate and transitory: start, arousal reactions, postural oculo-cephalo-motor response, cardiovascular reactions with tachycardia and peripheral vasoconstriction, mydriasis. The chronic reactions to an occupational permanent noise are mostly a state of fatigue, lowering of the psychotechnic ability, aggressivity, transitory tachycardia and elevation of blood pressure, mainly diastolic. The best argument in favour of a correlation between these reactions and the noise is their reversibility with the cessation of the nuisance. The non-auditive responses to noise--including blood pressure variation--described for stimuli of moderate intensity considered as environmental nuisances are less evident. Among inhabitants of a town the neurophysiological examination of the modifications due to different demonstrate the evident perturbation of the sleep organisation: difficulties to fall asleep, need of a complementary rest. The epidemiological inquiries in noisy zones indicate however that, within a common population, 10% of the subjects feel very uncomfortable, but that 30% of them declare to be normal. The revendications and the trials against the factors of noise let us recommend to associate the efforts of physicians and of physiologists to those of acousticians experts. The different sonometric assays, the methods used in order to decide if a noise is a nuisance are described and should be widely used to demarcate very quiet territories (climatic areas) and sectors to be improved. PMID- 1504863 TI - [Cardiovascular effects of noise]. AB - The circulatory response to noise is dominated by a peripheral blood vessels vasoconstriction, of greater magnitude when asleep than awake. Noise of lower frequency seems more able to produce this response. With repetition of the noise, adaptation and tolerance to it quickly appears. Meanwhile prolonged high level noise exposition induces an increasing prevalence of arterial hypertension among industrial workers. This increase is also clearly found in residential communities living near airports. Long-term exposure to noise is a dangerous nuisance, that can lead to an increase in arterial blood pressure and favour coronary artery disease development. PMID- 1504864 TI - [Noise, sleep and behavior]. AB - The negative effects of noise on sleep and behaviour have been related to three mechanisms: a physiological arousal (above a certain threshold of noise), an aversive reaction and an interference with non auditive neurophysiological and mental processes. The perturbation of verbal communication and the effects of sleep are the directly observable consequences. The negative effects of noise above a certain threshold on sleep have been demonstrated both in experimental conditions and in real life. They concern length, EEG pattern, and subjective quality and produce an increase of irritability and tiredness. There is no habituation. In all populations studied, strong discomfort is expressed by 50% of the subjects living in an area with an Ldn of 75 dB in the case of air traffic noise, the same results being obtained with ground traffic for a 5-15 dB higher level. Objective expressions of discomfort: use of aural protections, closing the windows, staying indoor, changing residence, increase linearly with the intensity of noise. Noise influences the incidence of stress-related disorders: hypertension, related cardio-vascular diseases, psychosomatic and psychological disorders. It has been shown by the use of different techniques (epidemiological studies based on the frequency of medical contacts, on the diagnoses made by general practitioners, on the use of specific drugs, and on the examination of the whole population) that the prevalence increases in relation with the level of noise in the vicinity of airports.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1504865 TI - [Noise: neuro-endocrine aspects]. AB - Experimental study of neuro-endocrinological effects of noise stress shows neuro mediator modifications. Exposure to stress induces a marked stimulation of the adrenergic structures which increases plasma concentrations of ACTH and glucosteroids. The increased secretion of the cortico-releasing factor (CRT) from the hypothalamo-hypophyseal system mediates a complex cascade in which other neuro-modulators also participate. Within the CNS, CRF activates the sympathetic nervous system, raising plasma concentrations of epinephrine and nor-epinephrine. These neuro-mediator and endocrine variations modify the activity of central nervous structures, mainly hypothalamic (endocrine) and hippocampic (emotion) formations, inducing many homeostatic perturbations. Stress also causes marked alterations in the immune function. In chronically noise-stressed patients, a comparative clinical study showed a significant increase of the plasmatic STH, but no modification of others biological parameters. Some psychosomatic disorders and also a psychological unbalance were seen in these patients. The final response to a stressful event will either be no or certain specific chemical and physiological changes which will depend greatly on the ability of the individual to cope with the outside stimuli. PMID- 1504866 TI - [Legal aspect: regulation]. AB - We gather, under the expression of regulation, both Parliament Acts and general texts emanating from executive Authorities. The analysis must be made according to the source of noise. So we have successively examined noisy equipment, industrial, commercial and agricultural activities producing noise, noisy material, carriage, leisure activities, building and neighbourhood noises, and after all the protection of working people. We have also studied the organization of the fight against noise, since it depends on law. Finally, this regulation is already very rich, including both texts directly concerning the fight against noise and other texts belonging to wider regulations (protection of environment or protection of working people). On the whole it seems to be well adapted to its objective, the prevention, even if it may be completed. The main thing is a better application to matters concerning everyday life and striking opinion, such as neighbourhood and traffic noises. It will be surely evolutive, first by connection with related and wider regulations, and above all according to the progress of our scientific and technical knowledge. Thus it will be constantly adapted, if exactly applied, to the needs of prevention. PMID- 1504868 TI - [Antibiotic residues and digestive microflora]. AB - Can antibiotic residues modify the human gut flora, and select drug resistant bacteria? In volunteers given ampicillin (1.5 mg/d) or oxytetracycline (2 mg/d), the fecal excretion of resistant enterobacteria was not changed significantly. However a possible effect would be hidden in human beings by the huge day to day fluctuations in the resistant bacterial populations. Heteroxenic mice (i.e. germfree mice associated with the flora of a human donor) and dixenic mice (i.e. mice harboring 2 isogenic strains, one of which carries an R-plasmid) are possible models to study the gut flora in vivo without contaminations and interfering factors. Minimum selecting doses in these models are between 0.5 and 10 mg antibiotic per liter of drinking water. These doses are smaller than what a consumer could ingest in food. Last, fecal resistant enterobacteria directly come from contaminated food, as shown by their clearance from stools of volunteers eating a sterile diet. Hence antibiotic residues do not modify significantly the gut flora. PMID- 1504867 TI - [Is nutritional intervention influencing lipid allowances beneficial?]. AB - An earlier study (consumption study) has shown that in subjects eating normally: 1) the amount of fat consumed per day corresponds to 4/5 of the fat contained in the portions served; 2) the distribution of the fatty acids (FA) consumed is unfavorable because of the use of saturated FA for food preparation and cooking and because of the elimination of mono- and polyunsaturated FA in the unconsumed food. In order to determine whether a simple nutritional intervention might favorably modify the distribution of FA consumed, a computer simulation of a decrease in allowances of saturated FA in exchange for an increase in mono- and polyunsaturated FA was tested. The laboratory results were compared to those of the computer program. Comparison of the intervention study with the consumption study revealed that: 1) the fat content was identical; 2) there were the same number of total calories, but there were more lipidic calories consumed during the intervention (38% instead of 35%); 3) the distribution of FA more nearly approached the recommended amounts: 40% saturated FA (-25%), 39% monounsaturated FA (+8%), 21% polyunsaturated FA (+91%) and a P/S ratio of .60 (instead of .21); 4) these proportions can be explained by a decrease in palmitic (-30%) and stearic (-20%) acids and by an increase in linoleic (+100%) and linolenic (+40%) acids; 5) the allowances of elaidic acid was on the average 4.3 g per day and had little influence on the P/S ratio; 6) the omega 6/omega 3 ratio (ratio of 7) was higher than that of the consumption study (ratio of 5); 7) there was a 16% decrease in cholesterol intake (260 mg instead of 310 mg). The laboratory findings corresponded on the whole to those of the computer program that only faulted by overestimating lipid and cholesterol allowances. PMID- 1504869 TI - [Utilization of blood arising from therapeutic bleeding of genetic hemochromatosis]. PMID- 1504870 TI - [Detection of HIV infection in centers and establishments of public and private care]. PMID- 1504871 TI - [Advertisements for the treatment of obesity or deceit without limits]. AB - In magazines the advertisements for slimming diets or products are more and more frequent. The study of these advertisements shows that most of them do not give any indication on the composition of products or on the nature of the proposed methods. The selling arguments are the most often fallacious: freely diminution of body weight without dieting and physical activities, lack of checks, no successive increase of body weight, dramatic and quick slimming, debatable informations on the mechanisms of actions. In addition these treatments are followed without medical supervision. They are the antithesis of the right therapeutics of obesities. The diffusion of these methods as that of the numerous books on the slimming diets or technics in various European countries requires a study in order to protect the patients against their exploitation and a proposal of legislation for the European Countries in the whole which will make up the future Great European Community. PMID- 1504872 TI - [Iatrogenic illness observed in the hospital environment. I. A report of 109 cases collected in a cross-sectional APNET study]. AB - In an "on a given day" study, we analysed the prevalence and causes of drug related and non-drug-related iatrogenic illnesses for educational and preventive purposes. Forty-three hospital departments of various specialties and involving 62 APNET members participated in the study. From a total of 112 cases reported, 109 were considered iatrogenic illnesses on the basis of the French criteria for adverse effects. Four major types of iatrogenic illness were defined, as follows: I--drug-related cases (n = 83); II--miscellaneous cases (n = 6); III--cases due to therapeutic instrumentation (n = 16); IV--cases due to diagnostic instrumentation (n = 4). Overall, 6.28% of the patients admitted presented an iatrogenic illness; 67 (61.46%) of the 109 cases concerned women and 66 (60.55%) concerned patients aged 65 years or more. The types of illness in the "drug induced" and "miscellaneous" categories were endocrine and metabolic disturbances (n = 14), gastrointestinal conditions (n = 13) and hematological disorders (11 cases of bone marrow aplasia). Instrument-related iatrogenic illnesses comprised cardiovascular conditions (n = 6), locoregional anatomic lesions (n = 5), infectious complications (n = 3), bleeding (n = 3) and others (n = 3). Seventeen incidents were benign, 38 dangerous and 51 serious; there were three deaths. The main drug categories concerned in the 89 cases of "drug-related" and "miscellaneous" iatrogenic illnesses were as follows: cardiovascular agents (n = 20), antiinflammatory and analgesic drugs (n = 18), hormone and nutritional treatments (n = 11) and neuropsychiatric drugs (n = 11). Instrument-related iatrogenic illnesses chiefly involved venous approaches (n = 8), surgery (n = 4), intensive care procedures (n = 2), renal dialysis (n = 2) and radiation therapy (n = 2). The main causes of drug-related iatrogenic illnesses were self-treatment (n = 8), poor compliance (n = 8), and therapeutic errors (n = 27) [non-respect of a contraindication (n = 2), wrong indication (n = 6), excessive dose (n = 13), over-prolonged treatment (n = 2) and other errors (n = 4). A cost-analysis of 74 of the 109 cases gave a minimum figure of 2 million French francs. The human and financial costs of iatrogenic illnesses show that risk-prevention measures are required; these will be dealt with in a later paper, but should be based on stricter regulations and educational programmes aimed at doctors, patients, the general public, the pharmaceutical industry and the health authorities. PMID- 1504873 TI - [Pheochromocytoma. Study of a personal series of 85 cases]. AB - The study of a personal series of 85 cases observed by the same endocrinologist over a period of 40 years shows the modifications of clinical presentation and biological methods of diagnosis and treatment. There is a striking increase in the percentage of patients without any cardiac or vascular manifestations. The methoxyamines assay has the best sensitivity and specificity even in asymptomatic tumors. The recent development of this assay in the blood is very efficient. The tumor may be found with an abdominal CT scan. The use of NMR is not fruitful. The 131I MIBG scintigraphy is necessary if the CT scan is not informative and in malignant forms. The malignancy is more frequent (16.5%) than classical according to the long duration of the disease. The quite good prognosis is improved by the administration of 131I MIBG. The surgery was safer and without mortality over the last 15 years. PMID- 1504874 TI - [Endemic goiter in the La Kara region (Togo). Analysis of etiologic factors]. AB - Among 6,035 people living in 3 villages from the area of La Kara (Togo), 984 randomized subjects were investigated to evaluate goiter prevalence and related etiologic factors. Creatinine and thiocyanates (SCN-) were measured in urine, thyroid hormones and TSH in plasma. Iodine was evaluated in urine, water, salt, soil, millet and sorgho. The amount of cassava was evaluated in food. Mean goiter prevalence was 32%, reaching to 45.9% in one village; urinary iodine remained in a low range (27.2 +/- 2.18 micrograms/g creatinine in adults, 34.3 +/- 6.7 in children--m +/- SEM) independently of the presence of endemic goiter. Urinary SCN was increased. Low iodine values were found in food, salt, soil and water which contained few mineral elements except flour which was increased in the samples collected in one of the 3 villages. Cretinism was absent, T4, T3, TSH remained in a normal range. This study confirms a high prevalence of endemic goiter in the area of La Kara with iodine deficiency, leading to an urgent iodine supplementation. PMID- 1504875 TI - [A new regulatory mechanism of the action of corticosteroid hormones: cellular 11beta-hydroxycorticosteroid dehydrogenase]. AB - Eleven-beta-hydroxysteroid dehydrogenase (11 beta OHSD) protects the aldosterone receptor (MR) against its occupancy by glucocorticoid hormones. We examined the intrarenal distribution of 11 beta OHSD, as compared to that of MR. MR were localized in histological sections from rabbit kidney, using immunohistochemical methods with an anti-MR monoclonal antibody. 11 beta OHSD activity was measured in isolated tubular segments from rabbit, rat and mouse kidneys. Tubules were incubated in the presence of tritiated corticosterone (3H-B:2 x 10(-8)M). Then the rate of degradation of 3H-B into 3H-11-dehydrocorticosterone (3H-A) was determined by HPLC. MR was immunodetected in the distal tubule and the collecting duct. No positive staining was present in the proximal tubule. The conversion rate of 3H-B into 3H-A was high (approximately 80%) in the distal and collecting tubule. It was low in the proximal tubule (less than 15%) except in the rat (approximately 50%). These results indicate that MR and 11OHSD are colocalized along the mammalian nephron. This colocalization constitutes a strong argument in favor of the MR-protective role of 11 beta OHSD, and of a role of a defect of this enzyme in the genesis of some types of arterial hypertension. PMID- 1504876 TI - The quality of caries data from the national and BASCD surveys. PMID- 1504877 TI - The burden of oral disorders in a population of older adults. AB - This paper describes the burden of oral disorders in a population of adults aged 50 years and over living independently in the community. In so doing it uses clinical, functional, experiential and psychosocial impact measures to document the oral health status of this section of the population. The data reveal that substantial proportions of subjects report that their quality of life was compromised in some way by oral problems. Although only 24.1 per cent were edentulous, 30.5 per cent were unable to chew one or more foods; 37.2 per cent reported oral or facial pain in the previous four weeks and 67.5 per cent experienced one or more other oral symptoms. One third reported problems with eating and communication--social interaction, 18.7 per cent worried a great deal about their oral health and 30.8 per cent were dissatisfied with some aspect of their oral health status. Income was consistently associated with all health status measures examined, demonstrating the scope of inequalities in oral health. In addition, regression analysis showed that low income groups had higher scores on a psychosocial impact scale after controlling for clinical, functional and experiential oral health indicators. The paper illustrates the utility of a model of disease and its consequences derived from the international classification of impairments, disabilities and handicaps in exploring oral health. PMID- 1504878 TI - Dental anxiety and oral health in young Israeli male adults. AB - Dental anxiety may be a serious limiting factor in providing adequate dental treatment. The present study sought to define the prevalence of dental anxiety in a cross-section of young Israeli adults (389 male Israeli army recruits) to correlate anxiety scores with their oral health status and to compare the findings with existing data. The main stimuli triggering anxiety were found to be in the following descending order: seeing the needle, feeling the drill, and feeling pain despite local anaesthesia. A positive correlation was found between the degree of anxiety and the dental status; the highest percentage of untreated patients was found in the high anxiety group. It is concluded that young adult Israeli males manifest dental anxiety in a manner similar to that reported in the United States and Sweden. Dental anxiety may be an important factor in the avoidance of seeking dental care. PMID- 1504879 TI - Two critical confounding factors in periodontal epidemiology. AB - The prevalence and severity of periodontitis is considerably lower than was previously estimated. The available epidemiological methods are based on the premise that loss of periodontal attachment is a unique sign of periodontitis. However, additional factors resulting in loss of periodontal attachment confound data obtained from modern studies. The physiological process of continuous tooth eruption results in loss of periodontal attachment over a lifetime, at an approximate rate of 0.1 mm/year. Anthropological and clinical evidence for continuous tooth eruption is reviewed. The position of the alveolar crest appears to be stable; loss of periodontal attachment occurs as the teeth erupt and less of the root is embedded in bone. Retrograde periodontitis caused by pulpal disease is a known cause of severe, localised destruction of periodontal tissues. Its signs and symptoms include periodontal pocket formation, purulent inflammatory exudates, angular bone loss, swelling and bleeding of the gingival tissues and increased tooth mobility. Anthropological, experimental and clinical evidence for retrograde periodontitis is discussed. Misdiagnosis of angular (hemiseptal), furcal and other forms of localised periodontal damage as periodontitis has probably resulted because of the inability to determine the quality of pulpal health and the assumption of a gingivitis-periodontitis continuum. New epidemiological methods need to be developed in which physiological and all pathological conditions which affect the periodontal attachment are recognised and appropriately categorised. PMID- 1504880 TI - Tooth surface loss and associated factors among factory workers in Finland and Tanzania. AB - The relative importance of various factors in the occurrence of tooth surface loss was explored in a, cross-sectional study using blind dental examinations. Two samples were drawn; one from Finland, comprising 186 workers from four factories and another from Tanzania of 180 workers from two factories. Among the 326 dentate individuals who participated, 164 were exposed to acid fumes and 162 were not. In Finland, people with tooth surface loss were older and smoked cigarettes less frequently. In Tanzania, those with tooth surface loss were also older and the proportion of subjects with the condition was significantly higher among people not using a commercial toothbrush and those exposed to acids. Among the Tanzanians, exposure to acids increased the probability of tooth surface loss to a high level of significance, and increasing age increased its probability, both among the Finns and the Tanzanians. Both anterior and posterior teeth were affected. It can be concluded that if the exposure to acids from the air breathed is high, the probability of tooth surface loss will increase. It seems that explanatory factors for tooth surface loss from one society cannot be extrapolated to another. PMID- 1504881 TI - A comparison between the dental health of 3-year-old children living in fluoridated Huddersfield and non-fluoridated Dewsbury in 1989. AB - A study was undertaken to compare the prevalence of dental caries and developmental defects of enamel between 3-year-old children who were lifelong residents of fluoridated areas of Huddersfield (1 ppm F) and non-fluoridated Dewsbury (less than 0.3 ppm F). An interview was also conducted with the parents of the children to provide information regarding previous dental experiences. The study populations were identified using the national child health system. The mean dmft was 0.30 in Huddersfield and 0.74 in Dewsbury. The percentage of children who had experienced dental caries and the percentage with carious teeth were significantly lower in the fluoridated area. The Dewsbury children had suffered more toothache. There was a significantly higher number of children in Huddersfield with diffuse enamel defects on their upper and lower first molars. This study has also demonstrated that the national child health system provides a method for obtaining a random sample of pre-school children from the general population, thus avoiding the problems associated with studies using selected populations. Fluoridation in Huddersfield ceased in October 1989 and it is hoped that this decision will be reversed as soon as possible. PMID- 1504882 TI - Provision of crowns in Scotland--a ten year longitudinal study. AB - The annual reports of the Scottish Dental Practice Board have shown a dramatic increase in the number of crowns provided in the general dental service between the years 1978 and 1988. This paper investigates the changes in crown provision for a sample of dentate adults in Scotland whose dental treatment records have been monitored longitudinally. One hundred and sixteen out of a sample of 720 patients received one or more crowns over the ten year period between 1978 and 1988. A total of 213 crowns were placed, the majority of which were constructed of porcelain. Forty eight of them were replacements for crowns which had been supplied prior to or during the study period. A preliminary life table analysis estimates the median survival time of the crowns to be at least 10 years. PMID- 1504883 TI - The oral health status and health behaviour of 12 and 15 year-old adolescents in Jakarta, Indonesia. AB - Indonesia is a developing country with few dental services and a population at risk to deteriorating oral health. Five hundred and ninety-one 12 and 15 year-old children drawn from a low fluoride (F- less than 0.1 ppm) urban area of Jakarta, Indonesia were examined for dental caries, fluorosis, and periodontal diseases. In addition, a questionnaire was administered investigating socio-demographic background, use of dental services, and preventive oral care. Although the severity of dental caries experience was moderate, untreated caries on the occlusal surface formed the highest proportion of the dental caries experience. CPITN examination revealed a large proportion of the subjects had calculus as their highest score, combined with a substantial number of sites which exhibited bleeding on probing. Questionnaire data revealed a high home use of fluoridated toothpaste by the subjects but a predominant use of dental services for pain relief. Findings from this study suggest a need for primary preventive programmes focusing on occlusal sealants and plaque control. PMID- 1504884 TI - The uptake and completion of dental treatment using a mobile clinic in central Birmingham, UK. AB - The provision of a mobile dental service at a primary school in a socially deprived, multi-ethnic area markedly increased the uptake and completion of treatment after a school dental inspection. Eighty one per cent of children who were offered treatment in the mobile clinic accepted it and 91 per cent of these completed it. In the previous year, when care was offered at a health centre within half a mile of the school, the corresponding figure was 43 and 4 per cent. Over half the children seen in the mobile clinic had not previously visited a dentist. PMID- 1504885 TI - House dust mite control with Acarosan--an extreme test? PMID- 1504886 TI - The beta-agonist controversy: fact or fiction? PMID- 1504887 TI - How useful are guinea-pig models of asthma? PMID- 1504888 TI - The effects of air pollution on allergic bronchial responsiveness. PMID- 1504889 TI - The Jack Pepys Lecture. The hypersensitivity reactions--some personal reflections. PMID- 1504890 TI - Mechanisms and patient compliance of dust-mite avoidance regimens in dwellings of mite-allergic rhinitic patients. AB - We report on the mechanisms, the environmental changes and patient compliance with regard to conventional and new dust and mite avoidance measures to prevent allergic symptoms caused by mite allergens, taking into account both allergen contamination and the developmental success of pyroglyphid Acari. Twenty patients with persisting rhinitic complaints were selected and matched. Although the patients had performed some conventional dust and mite avoidance measures (patient compliance was 90%), the dwellings proved to be a stimulus for mite development. Moisture problems due to faulty construction and excessive moisture production were common. Since humidity conditions could not be changed at short notice, the 20 homes were subjected to the new variants of mite allergen avoidance based on intensive cleaning without (control) and with an acaricide incorporated (acaricidal cleaner [Acarosan]). After the carrying out of conventional avoidance measures, these patients still had allergic symptoms, and dust from only 23 to 52% of their textile objects was under the proposed guanine (mite faeces indicator) risk level. Only the acaricidal cleaner was able to decrease the allergenic mite load (and the burden of the patients) significantly in this 12 month period. With respect to mite-extermination, acaricidal cleaning was 88% better than intensive cleaning. Reduction of guanine was 38% better in the Acarosan treatment group. Clinical results have been reported elsewhere. A significant difference in favour of the acaricidal cleaning was seen in both subjective (as regards symptoms) and in objective data (total IgE). Another 50 patients were questioned.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1504891 TI - Low dose fenoterol aerosol protects against histamine-induced bronchoconstriction in mild asthmatics: a dose response study. AB - Sixteen subjects with mild stable asthma participated in a randomized double blind study on the effects of low dose fenoterol against histamine induced bronchoconstriction. Fenoterol aerosol at concentrations of 10, 50 and 200 micrograms and placebo were delivered at random through a metered dose inhaler as a single dose 30 min before histamine challenges on four separate occasions. Compared to placebo a fenoterol dose of 10 micrograms provided significant bronchodilatation (sRaw [s.d.] 8.3 [2.73] vs 6.3 [1.74] cm H2O* s [P less than 0.05]) and protection (PC100 sRaw [s.e.m.] 0.72 (1.31) vs 1.45 (1.39) mg/ml). The bronchodilatory and protective actions of fenoterol were more pronounced after the inhalation of 200 micrograms (P less than 0.05) with no difference between 10 and 50 micrograms fenoterol aerosol. The magnitude of bronchodilatation and protection was not correlated (r = 0.15). The results from this acute study may suggest that fenoterol at doses up to 20 times lower than routinely recommended may be an effective treatment in mild asthmatics. PMID- 1504892 TI - Specific immunological and bronchopulmonary responses following intradermal sensitization to free trimellitic anhydride in guinea pigs. AB - We have developed a guinea pig model of trimellitic anhydride-induced airway hypersensitivity responses. In one group of guinea pigs, injected intradermally with 0.1 ml 30% trimellitic anhydride (TMA), we examined the specificity of the bronchopulmonary response to TMA comparing the effect of intravenous TMA conjugated to guinea pig serum albumin (GPSA) with a control hapten (procion dye) protein conjugate (PD-GPSA). A significant increase in pulmonary inflation pressure (PIP) was provoked in sensitized animals following intravenous injection with TMA-GPSA (20%; 0-400, median; range) as compared to intravenous injection of PD-GPSA. In the second group we compared three different methods of sensitization: single injection of 0.1 ml of 0.3% TMA; four injections of 0.1 ml of 0.1% TMA; and a single high dose injection of 30% TMA. Following intravenous TMA-GPSA guinea pigs sensitized with a single injection 0.3% TMA had an increase in PIP of 395%; 220-600, while those given four repeat injections of 0.1% TMA had an increase in PIP of 343%; 315-490. These results were significantly higher than the increase in PIP (160%; 0-220) which occurred in guinea pigs sensitized with a single dose of 30% TMA. Four of 11 guinea pigs given low dose injections of TMA had bronchopulmonary responses to inhaled TMA-GPSA. All sensitized guinea pigs had specific IgG1 antibodies demonstrated by enzyme linked immunosorbent assay (ELISA) and confirmed by ELISA inhibition. Four guinea pigs sensitized by low dose injections of TMA had IgE antibodies demonstrated by passive cutaneous anaphylaxis.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1504893 TI - Dynamics of mast cells in the nasal mucosa of patients with allergic rhinitis and non-allergic controls: a biopsy study. AB - Mast cell degranulation is thought to be an important component of the pathogenesis of allergic rhinitis. Quantitative studies on mast cells in nasal mucosa after allergen exposure have given widely divergent results, ranging from an overall decrease via redistribution to an overall increase. We investigated this problem by employing a combination of anti-IgE and toluidine blue staining of biopsy specimens. In allergic patients anti-IgE was found to identify all mast cells and toluidine blue to detect mast cells that were not (totally) degranulated. The study was composed of two parts done in different patient groups. In the first part of the study biopsies were performed in 23 patients with isolated grass-pollen allergy, once during natural provocation in the summer and once in the winter. Biopsies were also performed in 12 controls. Non-allergic controls were found to have the same number of mast cells in the lamina propria as asymptomatic allergic patients. The controls seldom have mast cells in the epithelium. The patients with isolated grass-pollen allergy showed an increase in the numbers of mast cells in the lamina propria during natural provocation and the same seemed to occur in the epithelium as well. During natural provocation almost all of the mast cells in the epithelium and half of those in the lamina propria were degranulated. In the second part of the study 17 patients with isolated grass-pollen allergy and four controls were challenged daily with allergen extract during a 2-week period in the winter. During this period biopsies were performed at eight different occasions, i.e. once before, six occasions during and once after the provocation period. The results of this part of the study showed that during provocation mast cells migrate to the surface of the nasal mucosa, where they become degranulated, and that the pool of mast cells in the lamina propria was apparently replenished by migration of mast cells from the vessels in the lamina propria. The total number of mast cells in the lamina propria remained approximately the same while the mast cells residing in an increasingly thick layer measured from the basal membrane into the lamina propria became degranulated. After 2 weeks, 82% of the mast cells in the lamina propria was degranulated and it was only in the deepest layers that some toluidine blue positive cells were found.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1504894 TI - Panic in the streets. PMID- 1504895 TI - Goodwill--your most valuable asset. PMID- 1504896 TI - The Stern ERA attachment. Exacting retention made easy. PMID- 1504897 TI - Getting patients to say yes: effective case presentations. AB - Getting patients to say yes to recommended treatment requires the dedication of each team member. It demands a commitment to educating patients and motivating them to turn their dental needs into dental wants, as well as providing financial options to make treatment affordable. When the dental team takes the time to nurture the case presentation process, the results can be dramatic. Patients embrace treatment and the practice provides it. It is nothing short of a win-win scenario. PMID- 1504898 TI - The ideal bonding system. PMID- 1504899 TI - Perio and practice management: the inextricable link. PMID- 1504900 TI - Working smarter not harder: maximizing your team's performance. PMID- 1504901 TI - Aptitude + attitude = success. PMID- 1504902 TI - The dental practice purchase/sale--creating a win-win transaction. AB - The importance of the dentist-patient/client relationship makes the dental practice purchase/sale unique compared with other business transactions. Dental practice goodwill can be easily lost, but establishing mutual trust between purchaser and vendor can lead to a win-win transaction through maximizing practice goodwill and minimizing associated taxes. Tax planning for the purchase/sale is complex, and, although this article has provided some basic information, professional advice is recommended. PMID- 1504903 TI - Leadership as the foundation of your practice. PMID- 1504904 TI - Oral pathology in Canada: a survey. AB - The Canadian Academy of Oral Pathology conducted a survey of its active members to obtain information on their demographics, professional activities and university affiliations, and to assess Canada's present and future oral pathology needs. Data were also collected on Canadian oral pathology diagnostic biopsy services. This paper reports the salient findings of the survey, and discusses their implications for the specialty of oral pathology as well as for the Canadian dental community. PMID- 1504905 TI - Vital tooth bleaching: review and current status. AB - Vital tooth bleaching refers to the clinical application of a chemical solution to a tooth surface in order to achieve a lightening effect. This article reviews the available literature to address the following questions: What are the methods of vital bleaching? How does vital bleaching work and is it effective? What effects are there on the teeth, dental restorative materials, soft tissues and systemic health? The techniques used in the application of dentist-applied and patient-applied bleaching systems are described. Generally, vital tooth bleaching has been found to be effective, however, relapse does occur. The literature suggests that bleaching agents may have transient effects on the tooth itself, and may affect some dental materials. Soft tissues exposed to hydrogen peroxide for prolonged periods show changes consistent with inflammation or hyperplasia. Hydrogen peroxide may also potentiate the carcinogenic effect of known carcinogens. However, more clinically relevant studies are needed. Until long term safety data becomes available, the dental practitioner should approach the use of in-home bleaches with caution. The U.S. Food and Drug Administration (FDA) recently classified these products as "new drug." However, dentist-applied bleaching gel systems are a viable alternative and deserve further consideration. They are simple to use, require little armamentarium, and limit the exposure of the bleaching agent to the teeth only. Vital tooth bleaching refers to the clinical application of a chemical solution to a tooth surface in order to achieve a lightening effect. There was a resurgence of interest in vital bleaching with the recent introduction of the in-home bleaching technique.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1504907 TI - Canadian task force on cardiovascular science. PMID- 1504906 TI - A preliminary comparative study of the retentive properties of four post and core systems in etched preparations. AB - Post and core systems anchored and supported by endodontic files, Para Posts, Boston Posts and Flexi Posts were subjected to tensile testing in an Instron testing machine. All forces were applied to the cores until the post-core system was removed. The test results revealed no statistically significant difference among post and core systems built up with Para Posts, Boston Posts or Flexi Posts. The endodontic files proved to be significantly less retentive than the other post systems evaluated. Under the conditions of this study, the use of endodontic files as retentive posts is not supported. PMID- 1504908 TI - Abdominal obesity and the risk of coronary artery disease. PMID- 1504909 TI - The J-curve--it is clinically relevant? PMID- 1504910 TI - Perinatal supraventricular tachycardia. AB - OBJECTIVE: To determine the incidence, therapy required and prognosis of perinatal supraventricular tachycardia (SVT). DESIGN: Retrospective chart review of eight years. SETTING: Tertiary level perinatal and pediatric centres in Halifax, Nova Scotia. PATIENTS: All newborn infants who developed SVT either in utero or in the first 30 days of life. RESULTS: SVT was present in 33 neonates, with a male:female ratio of 2.7:1 and an incidence of 1:4347. Fetal SVT was recorded in nine (group I) but these patients did not differ from those with postnatal SVT (group II) in birthweight, noncardiac illnesses and associated heart disease. Thirty-one of the babies (94%) received digoxin and eight (24%) also required propranolol. All were asymptomatic after 48 h. One late death occurred due to renal failure unrelated to the dysrhythmia. No major congenital heart disease was found in either group. Follow-up over 44 months revealed four late relapses requiring prolonged therapy. CONCLUSIONS: Perinatal SVT is a common disorder in a tertiary centre and may represent a transient adaptation phenomenon. It is usually benign, easily treated and rarely associated with major congenital heart disease. PMID- 1504911 TI - Migration and imaging of 111Indium-labelled lymphocytes in cardiac allograft rejection. AB - BACKGROUND: The diagnosis of cardiac allograft rejection is based on routine endomyocardial biopsy. To study an alternative method the authors evaluated the migration and scintigraphic imaging of 111Indium-labelled lymphocytes in a model of acute heart allograft rejection. METHODS AND RESULTS: Cervical heterotopic heart transplantation was performed in 10 dogs. Blood samples were harvested at 24 and 48 h after surgery for labelling of 36 +/- 6 x 10(6) lymphocytes with 6.62 +/- 0.56 MBq of 111Indium. Daily blood samples and heart biopsies were obtained for nuclear counting on the next three days; animals were sacrificed and both donor and native hearts were studied. Between 20 and 31% of autologous labelled lymphocytes remained in circulation until 72 h after injection. Maximal plasma 111Indium activity was 315 +/- 90 compared with 5513 +/- 1483 cpm/mL in whole blood (P less than 0.05). An average of 10,176 +/- 3444 labelled lymphocytes per gram of tissue were present in allograft biopsies while histological evaluation showed mild to moderate acute rejection. The ratio of tissue biopsy to blood 111Indium counts varied from 0.7 +/- 0.2, 6 h after autologous injection to 8.5 +/- 3.8 48 h later (P less than 0.05). At autopsy, 298 +/- 66 labelled cells per gram of tissue were present in native hearts compared with 2686 +/- 711 in allografts (P less than 0.05). Scintigraphic imaging using holospectral acquisition was performed; six lateral projections showed an indium activity ratio (transplanted heart to background tissue) of 2.8, 24 to 72 h after autologous injection of labelled cells. CONCLUSIONS: Labelling of a small number of lymphocytes with 111Indium gave a stable population of circulatory lymphocytes for studying migration of labelled cells into allografts and a noninvasive scintigraphic approach to diagnose cardiac allograft rejection. PMID- 1504912 TI - Annulo-aortic ectasia extending to the arch: composite graft repair with circulatory arrest. AB - OBJECTIVE: To examine the results of surgery performed in patients with annulo aortic ectasia extending to the arch. DESIGN: Retrospective hospital record review. SETTING: A Canadian teaching hospital. PATIENTS: Five patients (mean age 57 years) had annulo-aortic ectasia with severe aortic insufficiency, a maximum aneurysmal diameter ranging from 6.5 to 13 cm at the root or ascending aortic level, and extending into the arch with a diameter of at least 5 cm at the innominate artery level. They all had reconstruction with a composite prosthetic valve and Dacron tube graft employing standard techniques of aortic root replacement as well as aortic arch reconstruction with a single bevelled anastomosis in a state of profound hypothermia and circulatory arrest. MAIN RESULTS: No perioperative deaths, neurological complications nor significant cardiac complications. At a median follow-up period of 46 months all patients are alive, free from cardiovascular symptoms and show no evidence of aortic aneurysmal disease. CONCLUSIONS: This safe, effective and durable repair should be applied to selected patients with annulo-aortic ectasia which extends to the arch. PMID- 1504913 TI - The antiarrhythmic effect of the ACE inhibitor captopril in patients with congestive heart failure largely is due to its potassium sparing effects. AB - OBJECTIVE: To evaluate the mechanisms by which the angiotensin converting enzyme (ACE) inhibitor captopril may modify the presence of ventricular arrhythmias in patients with chronic heart failure. PATIENTS: Forty-seven patients with chronic stable congestive heart failure. METHODS: Twenty-four hour Holter monitoring was done prior to and after one month of therapy with the ACE inhibitor captopril. In a first group of 25 patients, changes in the incidence of ventricular arrhythmias were correlated with changes in cardiac hemodynamics (assessed invasively). In a second group of 22 patients, changes in ventricular arrhythmias were correlated with changes in echocardiographic measurements. In all patients serum potassium was kept constant, and changes in exercise tolerance and serum noradrenaline levels were assessed prior to and after captopril. RESULTS: One month of captopril therapy caused an improvement in cardiac hemodynamics and in exercise tolerance. It also led to a tendency for improved echocardiographic measurements and serum noradrenaline levels, similar to those already published by others. However, no change in the incidence or severity of ventricular arrhythmias was detected. No correlation could be found between changes in ventricular arrhythmias and any of the variables measured. CONCLUSIONS: As the only obvious difference between this and previous studies that documented a decrease in ventricular arrhythmias when ACE inhibitors were started in patients with congestive heart failure is a lack of change in serum potassium in this study, the current results suggest that the major antiarrhythmic effect of ACE inhibitors in patients with congestive hear failure is the result of their potassium sparing effects. PMID- 1504914 TI - In vitro interactions between low density lipoprotein from hyperapobetalipoproteinemic plasma and arterial wall proteoglycans. AB - OBJECTIVE: To examine the interactions of low density lipoprotein-B (LDL-B) with proteoglycans (PG) in vitro. DESIGN: The PG were isolated from human aortas, removed at autopsy by a combination of extraction with 4M guanidine-Tris buffer containing protease inhibitors and fractionation on a DEAE-Sephacel ion-exchange chromatography column. LDL and LDL-B from healthy or hyperapobetalipoproteinemic sera, respectively, were isolated by standard density flotation techniques followed by radioiodination. Radiolabelled lipoproteins (LP) were incubated with proteoglycans at 4 or 37 degrees C in a low ionic strength buffer with or without addition of polyethylene glycol (PEG) which was used to enhance precipitation of the resulting LP-PG complexes. MAIN RESULTS: Data revealed that a specific ratio of LP to PG is a prerequisite for optimal interactions between these macromolecules. Further, it was observed that LDL-B forms fewer precipitable complexes than normal LDL at 4 degrees C. However, at physiological temperature or with the addition of PEG, precipitation of the two LDLs was equal. CONCLUSION: LDL and LDL-B showed equal reactivity with PG in terms of precipitable complexes. PMID- 1504915 TI - [Reintegration to work in persons having survived a myocardial infarction: current review and ways of development for clinical interventions]. AB - The main purpose of this article is to update the state of knowledge regarding work reintegration following myocardial infarction. Occupational perspectives have greatly evolved during the second half of this century. This can be attributed mainly to a better understanding of the pathology itself and to a development of new therapeutic avenues which are part of a more global vision of the bio-psycho-social characteristics of the patient. The authors did not intend to realize an extensive review of the literature on the subject, but analysed the most significant articles published over the past 20 years. They were selected because of their frequent citation on the scientific literature which seems to confirm their significance and credibility. Following the analysis of the articles selected, the authors conclude that the scientific community has reached a consensus to the effect that the general evolution of the patient post myocardial infarction is greatly determined by psychosocial factors. It follows that comprehensive rehabilitation programs despite their limited impact in an experimental setting offer some stimulating perspectives. They suggest that some research effort be oriented towards the evaluation of the actual long term outcomes of rehabilitative programs especially on quality of life in general and on quality of life at work more specifically. PMID- 1504916 TI - Opioid receptor agonists D-Ala-2-Me-Phe-4-Met-(O)-ol enkephalin and ethylketocyclazocine in the brain accentuate digoxin-induced arrhythmias. AB - OBJECTIVE: To examine the potential effects of two opioid receptor agonists in the brain on digoxin-induced cardiac arrhythmias and to explore cholinergic mechanisms in any potential effect on arrhythmias. METHODS AND RESULTS: Digoxin induced arrhythmias were produced in guinea pigs (weighing between 280 and 350 g) that received digoxin 50 micrograms/kg intravenous bolus plus digoxin 500 micrograms/kg/h intravenously. Animals received D-Ala-2-Me-Phe-4-Met-(O)-ol enkephalin (FK 33,824) (50 or 100 micrograms/kg), ethylketocyclazocine (EKC) (50, 10 or 1 micrograms/kg) or saline (control) into the lateral cerebroventricle prior to digoxin. FK 33,824 produced significant (P less than 0.05) dose dependent reductions in the threshold for digoxin-induced arrhythmias. The mean digoxin dosage at the development of fatal arrhythmias after the 100 micrograms/kg of FK 33,824 was 30% lower than the control group. EKC also produced significant (P less than 0.05) dose-dependent reductions in the threshold for digoxin-induced arrhythmias and the mean dose at development of fatal arrhythmias was 67% lower than the control group after 50 micrograms/kg of EKC. In the absence of digoxin, the highest dosages of each of these opioids did not produce arrhythmias. Changes in blood pressure and heart rate were unlikely explanations for the observed actions of these opioids because D-Ala-2-Me-Phe-4 Met-(O)-ol enkephalin accentuated the increase in blood pressure that accompanied digoxin while EKC reduced the blood pressure response to digoxin and neither altered the heart rate response to digoxin. In the control group, fatal digoxin induced arrhythmias were ventricular tachyarrhythmias in two-thirds of cases and complete heart block in the remainder. These opioids accentuated the development of complete heart block. The role of the cholinergic system was explored for only EKC because both opioids produce similar effects on arrhythmias, using atropine sulphate which crosses the blood brain-barrier and atropine methylnitrate which does not enter the central nervous system. Atropine sulphate, but not atropine methylnitrate, slightly blunted but did not reverse the action of EKC. CONCLUSIONS: These data indicate that: two opioids in the brain--D-Ala-2-Me-Phe-4 Met-(O)-ol enkephalin and EKC--alter the threshold for development of digoxin induced arrhythmias, specifically accentuating development of complete heart block produced by digoxin; and cholinergic mechanisms play only a small role in modulating the action of EKC on digoxin-induced bradyarrhythmias. PMID- 1504917 TI - Slow rehydration improves the recovery of dried bacterial populations. AB - Slow rehydration of bacteria from dried inoculant formulations provided higher viable counts than did rapid rehydration. Estimates were higher when clay and peat powder formulations of Rhizobium meliloti, Rhizobium leguminosarum biovar trifolii, and Pseudomonas putida, with water activities between 0.280 and 0.650, were slowly rehydrated to water activities of approximately 0.992 before continuing the dilution plating sequence. Rhizobium meliloti populations averaged 6.8 x 10(8) cfu/g and 1328 cfu/alfalfa seed greater when slowly rehydrated from bulk powder and preinoculated seeds, respectively. Bulk powder samples were slowly rehydrated to 0.992 water activity by the gradual addition of diluent, followed by a 10-min period for moisture equilibration. Preinoculated seed samples were placed in an environmental chamber at 24 degrees C with relative humidity greater than 80% for 1 h to allow moisture absorption. "Upshock," osmotic cellular stresses that occur during rehydration, was reduced when dried microbial formulations were slowly rehydrated and equilibrated before becoming fully hydrated in the dilution plating sequence. These procedures may also be applicable when estimating total viable bacterial populations from dried soil or other dry formulations. PMID- 1504918 TI - Synthesis of the ferredoxin-like protein FdxN from Rhizobium meliloti bacteroids as a fusion protein in Escherichia coli. AB - To analyze the overexpression of the Rhizobium meliloti fdxN gene in Escherichia coli, different translational and transcriptional fusions were constructed. The translational signals of R. meliloti fdxN were recognized in E. coli as demonstrated by the use of in-frame lac fusions. Translational fusions consisting of the lacZ or the lpp gene fused in frame to the 3' end of the entire fdxN gene were expressed at high levels in E. coli. In contrast, the wild-type R. meliloti FdxN protein without a C-terminal fusion could only be detected using the very sensitive T7 promoter-polymerase system and not in immunoblots with antibodies against an FdxN-LacZ hybrid protein. Evidently, translational fusions to the 3' end of fdxN had a stabilizing effect on the expression of the fdxN gene. A constitutively expressed transcriptional fdxN fusion, which did not mediate detectable amounts of FdxN protein either in E. coli or in free-living R. meliloti cells, complemented the Fix- phenotype of an R. meliloti fdxN::[Tc] mutant strain to wild-type levels. Therefore, either low amounts of the wild-type FdxN protein are sufficient for symbiotic nitrogen fixation or there are stabilizing factors, which are present only in R. meliloti bacteroids but not in free-living R. meliloti cells. Fusion proteins consisting of FdxN and LacZ or a partial Lpp protein restored the Fix- phenotype of an R. meliloti fdxN mutant to 3 and 11%, respectively, indicating that a C-terminal fusion did not completely abolish the function of FdxN. PMID- 1504919 TI - Similarities between legume-rhizobium communication and steroid-mediated intercellular communication in vertebrates. AB - Regulation of the actions of flavonoids and Nod factors in legume-rhizobia communication has several interesting similarities with that of steroid-mediated actions in vertebrates. Oxidation or reduction of flavonoids and Nod factors modifies their biological activity just as, for example, oxidation of an alcohol at C11 on hydrocortisone regulates its biological activity. Second, some flavonoids are anti-inducers, functioning like steroid antagonists to negate the actions of inducer flavonoids. Amino acid sequence analyses show that human 17 beta-hydroxysteroid dehydrogenase, which catalyzes the interconversion of the alcohol and ketone at C17 on estrogens and androgens, and rat 11 beta hydroxysteroid dehydrogenase, which catalyzes the interconversion of the alcohol and ketone at C11 of glucocorticoids, and Rhizobium meliloti NodG and Bradyrhizobium japonicum. FixR are derived from a common ancestor. Just as steroid-metabolizing enzymes can regulate steroid-mediated gene transcription, enzymes that modify substituents on flavonoids and Nod factors may have a similar role in regulating signalling between legumes and rhizobia. The enzymes that modify flavonoids and Nod factors have not yet been identified. However, NodG and FixR are two likely candidates to have this role in regulating legume-rhizobia signalling. PMID- 1504921 TI - Cutaneous melanoma. PMID- 1504920 TI - Overexpression of the dctA gene in Rhizobium meliloti: effect on transport of C4 dicarboxylates and symbiotic nitrogen fixation. AB - Symbiotic nitrogen fixation may be limited by the transport of C4 dicarboxylates into bacteroids in the nodule for use as a carbon and energy source. In an attempt to increase dicarboxylate transport, a plasmid was constructed in which the Rhizobium meliloti structural transport gene dctA was fused to a tryptophan operon promoter from Salmonella typhimurium, trpPO. This resulted in a functional dctA gene that was no longer under the control of the dctBD regulatory genes, but the recombinant plasmid was found to be unstable in R. meliloti. To stably integrate the trpPO-dctA fusion, it was recloned into pBR325 and recombined into the R. meliloti exo megaplasmid in the dctABD region. The resultant strain showed constitutive dctA-specific mRNA synthesis which was about 5-fold higher than that found in fully induced wild-type cells. Uptake assays showed that [14C]succinate transport by the trpPO-dctA fusion strain was constitutive, and the transport rate was the same as that of induced control cells. Acetylene reduction assays indicated a significantly higher rate of nitrogen fixation in plants inoculated with the trpPO-dctA fusion strain compared with the control. Despite this apparent increase, the plants had the same top dry weights as those inoculated with control cells. PMID- 1504922 TI - Cutaneous melanoma. Commentary. PMID- 1504923 TI - Melanoma management. PMID- 1504924 TI - Discerning individuals at elevated risk for cutaneous melanoma. PMID- 1504925 TI - Precursor lesions to melanoma. PMID- 1504926 TI - Melanoma genetics and cytogenetics. PMID- 1504927 TI - Melanoma and ultraviolet radiation. PMID- 1504928 TI - Historical overview of melanoma. PMID- 1504929 TI - Nonsolar factors in melanoma risk. PMID- 1504930 TI - Immunologic factors in melanoma. PMID- 1504931 TI - Hormonal and reproductive factors in melanoma risk. PMID- 1504932 TI - Dietary factors in the etiology of melanoma. PMID- 1504933 TI - Human models of melanoma. PMID- 1504934 TI - Trends in melanoma incidence and mortality. PMID- 1504935 TI - Public and professional educational exercises on melanoma. PMID- 1504936 TI - Screening for melanoma and other skin cancers. PMID- 1504937 TI - Epidemiology of dental diseases in the elderly. AB - The aging of the American population will have enormous social ramifications, among which will be a greater focus on the elderly patient. Traditionally, the dental status of this group has been extracted teeth and full dentures, but that is now steadily changing. There were 41.1% of Americans aged 65 or older who were edentulous in 1985 to 1986, but a good proportion of them have been edentulous for many years. The prevalence of total tooth loss will continue to decline with time. The growth of a dentate elderly population, however, leaves more of that group at risk of caries. Caries, once seen as a disease of childhood, is now clearly a lifelong disease. Elderly persons are particularly at risk of root caries, which follows as a consequence of periodontitis. Total tooth loss and severe caries are both associated with lower socioeconomic status. Although cross sectional survey data invariably show, on average, a greater extent of periodontitis among older than among younger persons, periodontitis is not considered a disease of aging. The age difference in surveys is not because of greater susceptibility among the elderly but represents disease accumulated over time. Limited longitudinal data suggest that rapid loss of periodontal attachment, serious enough to threaten the dentition, is found in 7% to 15% of any population. But this group exhibits the disease when young. Those who have retained a more-or-less intact dentition into old age rarely exhibit a sudden onset of periodontitis. If such a change is seen it could be indicative of broader changes in the immune system. PMID- 1504938 TI - Oral and dental problems in the elderly. PMID- 1504939 TI - Epidemiology of nondental oral disease in the elderly. AB - This article presents the descriptive epidemiology, risk factors, and clinical highlights of the oral mucosal lesions that are most common or of greatest concern among the elderly. Leukoplakia, oral cancer, candidiasis, lichen planus, and RAU have not been studied extensively among the elderly. Recent efforts to standardize definitions and research methods should greatly enhance future information. The paucity of research on oral lesions such as herpes zoster, epulis, and oral medication reactions is surprising, given that these are common problems among the elderly. PMID- 1504940 TI - Oral sequelae of common geriatric diseases, disorders, and impairments. AB - The oral cavity is responsible for two essential functions: the production of speech and the initiation of alimentation. All of the specialized oral tissues and sensory systems that allow for the execution of these functions are susceptible to age-, disease-, and treatment-related changes, and alterations in any one or more function may result in deleterious consequences to the host and impact on the quality of life. Oral physiology is generally believed to be age stable in healthy individuals; however, in the presence of single or multiple medical diseases and their treatment, these functions deteriorate. This article focuses on the influence of common geriatric diseases, disorders, and impairments on oral health and function. Data are presented to suggest that oral health is altered in the presence of heart, cerebrovascular, liver, and renal diseases, cancer, COPD, diabetes, pneumonia, and influenza. Arthritic, hearing, visual, orthopedic, and speech impairments multiple medical problems. Finally, adjustments in treatment and management strategies may be necessary for older patients with these diseases and impairments. PMID- 1504941 TI - Salivary gland dysfunction. AB - Clinically significant declines of salivary output are not a function of aging. Complaints of oral dryness (xerostomia) are common in the elderly patient, however. This complaint is most often a consequence of medications; tricyclic antidepressants, certain antihypertensives, and anticholinergics can cause marked decreases in salivary flow rates. Other medications such as diuretics may cause xerostomia without decreasing salivary output. Systemic diseases such as Sjogren's syndrome can destroy salivary glands. Specific serologic, ophthalmologic, and salivary findings are necessary for the diagnosis of Sjogren's syndrome. Radiation therapy for treatment of head and neck cancers also can damage salivary glands permanently. Infectious agents such as mycobacteria, Epstein-Barr virus, and various oral bacteria can infect human salivary glands. Diminished salivary output can lead to serious oral sequelae. Rapidly progressing dental caries and oral candidiasis are found frequently in this age group. Close supervision of the geriatric patient's oral and dental health is essential. PMID- 1504942 TI - Oral candidiasis. AB - Candida spp. can frequently cause oral infections in the elderly. A number of factors, including yeast virulence factors and compromised host defenses, contribute to outcomes of clinical disease. Precise mechanisms that determine the varied clinical appearances of oral candidiasis have not been delineated fully. Oral candidiasis should be suspected at the clinical level when oral mucosal lesions consistent with the various presentations of candidiasis are observed in patients at risk. Culture remains the gold standard for assessment, although results may be equivocal. Topical or systemic antifungal therapy may result in resolution of symptoms and lesions, but lesions may recur if underlying risk factors remain. PMID- 1504943 TI - Precancerous lesions and oral cancer in the elderly. AB - Oral cancer is closely related to growing old, with over 95% of all cases occurring in individuals over age 40. In spite of advances in treatment, 5-year survival rates remain poor. Therefore, improvement in prevention and control of oral cancer is critically important. This can be accomplished through (1) reducing risks by avoiding tobacco and alcohol; (2) recognizing and treating premalignant lesions; and (3) early detection of developed oral cancers. PMID- 1504944 TI - Taste and smell. AB - Olfaction declines dramatically with age. Taste is relatively robust. A variety of causes other than aging are known to produce declines in olfaction and to a lesser extent in taste. Many chemosensory deficits in the elderly cannot be attributed to age but rather to pathologic conditions. In addition to deficits, individuals may experience taste or smell phantoms. In many cases, losses and phantoms are untreatable but their effects on the elderly may be mitigated by appropriate coping skills. PMID- 1504945 TI - Orofacial pain. AB - Orofacial pain is an area of considerable interest in aging. Orofacial nociceptive pain arises mainly from injury or disease afflicting the teeth or the supporting structures of the teeth (periodontium); however it may arise from other intraoral or nonintraoral structures. Because of the rich innervation of the orofacial complex, pain may be referred to remote sites. Neuropathic pains, such as trigeminal neuralgia and postherpetic neuralgia, result from nerve injury and are usually seen only in older adults. Establishment of the source and cause of the pain results in effective pain management. PMID- 1504946 TI - Oropharyngeal dysphagia in the elderly. AB - Considerable evidence exists to suggest that normal aging alone does not cause significant impairment to the ability to swallow. Although there are changes in muscular tension, speed of responses, taste sensitivity, and smell, the physiology of swallowing remains relatively intact. There is evidence suggesting that the duration of the oropharyngeal swallow is longer in older females and that esophageal motility slows in normal aging. Elderly persons do produce multiple lingual gestures and may eat softer and less spicy foods. These changes are subtle and subclinical but do not indicate oropharyngeal dysphagia. Oropharyngeal dysphagia in the elderly is the specific result of a pathologic condition or illness that may occur more commonly in elderly persons. These conditions are neurologic, neuromuscular, systemic, immunologic, psychiatric, environmental, or societal in nature. Oropharyngeal dysphagia is commonly found in institutionalized elderly populations and presents an ethical dilemma in treatment. PMID- 1504947 TI - General dental care for the elderly. AB - In order to provide the highest level of quality medical care, the physician must be knowledgeable about problems related to the oral cavity. In particular, the physician should understand how to identify specific oral and dental problems such as caries, periodontal disease, and mucosal lesions, refer to and consult with dental health professionals regarding oral health issues, and be aware of the range of dental treatment modalities for oral and dental problems. PMID- 1504948 TI - Considerations for physicians caring for older adults with periodontal disease. AB - Periodontal disease is a generic term encompassing a variety of inflammatory conditions affecting the supporting tissues of the teeth. Periodontitis is inflammation associated with net resorption of supporting alveolar bone and periodontal ligament. Gingivitis is inflammation limited to the covering gingival tissues and does not directly lead to tooth mobility or loss. Periodontal diseases are very prevalent. Because the bone and ligament resorption are essentially irreversible, accumulated tissue damage of periodontitis is reflected in a prevalence and severity that increase with age. Periodontitis is not caused by aging per se but by a complex host-parasite relationship in which specific pathogens among the subgingival microbiota not only injure tissues directly but stimulate a cascade of inflammatory mediators to damage host tissues. Analytic epidemiology has identified several risk indicators for advanced periodontitis in older adults. These are microbiologic (prevalence of certain anaerobes in the microbiota), behavioral (tobacco smoking and infrequent professional dental care), medical (older age, preexisting and generalized periodontitis, gingival bleeding), and social (financial worries). Periodontitis in older adults is treated by reducing the impact of these risk indicators. The infections are controlled by combinations of debridement, antimicrobial agents, and surgical procedures as indicated. Medically well older adults can be treated similarly to younger adults. Management of periodontal conditions can be complicated for patients who are medically compromised. Communication between physicians and dental personnel is often required to ascertain the medical history and list of medications taken by older patients. Many of the medications prescribed for medical problems associated with aging impact on treatment choices for managing periodontitis. Moreover, periodontists frequently prescribe analgesics, antibiotics, and anti-inflammatory agents that might interact with others among the numerous drugs taken by older patients. Older adults with cognitive or physical disabilities have special needs for individualized hygiene instruction and implements. Periodontal health promotion and improving access to periodontal care for the elderly are challenges, because dental services are most often in the private sector and dental insurance does not often apply after retirement. Because they grew up in an era in which tooth loss due to "gum" diseases was considered inevitable, their current motivation toward regular preventive care must be improved by removing barriers and impediments to care. In addition to life-threatening medical conditions, frail individuals institutionalized in collective living centers face compounded problems concerning the provision of adequate, not even optimal, dental care. Their periodontal health often deteriorates rapidly after institutionalization, and in some instances it can possibly predispose to aspiration pneumonia or other disseminated infections.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1504949 TI - Oral and maxillofacial surgical therapy for the older adult. AB - Older adults can present with a wide range of oral and maxillofacial diseases and conditions, and many of these are best treated surgically. One of the distinguishing features of geriatric surgery is the large percentage of older adults who have medical conditions that must be planned for perioperatively. Good communication between the surgeon and the primary care physician is important for this perioperative management. Orofacial infections, the most common of which are odontogenic in origin, require some form of surgical treatment and may or may not require treatment with antibiotics. Preprosthetic and reconstructive surgery may be necessary to treat the sequelae of oral and maxillofacial fractures, the sequelae of tooth loss, or surgical defects incurred during the treatment of cancer, osteomyelitis, osteoradionecrosis, or disorders of the TMJ. PMID- 1504950 TI - Conventional and implant oral prostheses. AB - Despite advances in preventive dentistry, many elderly persons present with several missing teeth replaced by oral prostheses of various kinds. An increasing number of prostheses are retained and supported by oral implants. Maintaining a complete dentition with fixed, removable, or implant-retained prostheses improves function and patient self-esteem. Irrespective of the prosthesis type, periodic functional and health reassessments are necessary. Strict oral hygiene protocols must be reinforced continually and appropriate modifications (relines) and repairs should be performed to prevent possible degeneration of supporting structures. Although implants promise enhanced function and greater patient satisfaction, they too require careful maintenance. Thus, all oral prostheses require close monitoring and maintenance care. A physician can make an important contribution to a patient's health and quality of life by ensuring that he or she receives routine oral health care. PMID- 1504951 TI - Oral health and the quality of life. AB - The study of the impact of oral diseases and conditions on individuals and societies has been slow to develop but has made major progress during the 1980s. Not only did improvements in understanding oral quality of life require developing and using more social and behavioral outcome measures, it required reassessing clinical indices. Reports on oral quality of life to date are often based on investigations that originally had other purposes; consequently there is inconsistent evidence about the associations among oral health, general health, and quality of life. In fact, in much of the cited literature the evidence is equivocal. Yet, in more recent research designed specifically to investigate quality of life (Meei-Shia Chen, PhD, personal communication, 1991), it is evident that orofacial conditions, diseases, and pain can be disruptive and can have considerable impacts at both the individual and societal levels in terms of reduction in normal activities; conversely, medical and social conditions can affect oral health. It is notable that across studies there is an incongruence between health care professional and patient assessments of quality of life--they view the issues differently. Although oral diseases are very prevalent, the early symptoms are often not severe, leading many individuals to disregard them, or if acknowledged, to define them as normal or unimportant. This may reflect a form of fatalism, i.e., their oral health is as good as could be expected. It is necessary to assess oral health and quality of life over time. Individuals indicating satisfaction or dissatisfaction with appearance, function, and self esteem at one point in time are doing so against a framework of immediate or long term expectations. In regard to specific procedures, such as surgery or dentures, it is necessary to know what the individual expects if the health care professional is to provide improvements in perceived and actual quality of life. Similarly, it is difficult to provide meaningful interpretation of self-assessed physical and social functioning and appearance against clinical measures, if the level of earlier dysfunction is not known. For example, in the case of full denture wearers, the evidence might be interpreted to suggest that these individuals have excellent oral quality of life. Without taking into account the extent of physical and social dysfunction and poor appearance prior to the dentures, and the consequent improvement against this base, it is impossible to evaluate and consequently improve quality of life. Understanding this process requires longitudinal studies.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1504952 TI - Problems in oral health care financing for the elderly. AB - The oral health of America's aged has improved dramatically. As the number of elderly swell, their collective need and demand for comprehensive dental services will increase significantly. Payment for those services will pose problems for many, because few options exist for financing dental care among the elderly. Currently most charges are covered by individuals out-of-pocket. Although more older people than ever before have sufficient funds to include dental visits in their health services use, a large proportion of the elderly lack the personal resources necessary to have their numerous dental conditions treated. Innovation is critical. Greater public and private sector support for accessible and affordable dental services must be offered in the future to ensure that the oral health gains of the past decades are not lost because of a lack of financial mechanisms for supporting an adequate level of care. PMID- 1504953 TI - The meaning of quality of life for bone marrow transplant survivors. Part 2. Improving quality of life for bone marrow transplant survivors. AB - Surviving bone marrow transplant (BMT) represents a major victory against malignant disease but also creates challenges of survivorship for patients and the professionals who care for them. Part 2 of this report presents the findings of a qualitative study (N = 119) related to improving quality of life (QOL) for BMT survivors. Results are shared based on BMT survivors' perceptions of (a) what makes QOL better, (b) what makes QOL worse, and (c) what doctors or nurses could do to enhance QOL. The findings of the study have been useful in constructing a quantitative instrument to measure QOL in BMT and in understanding the conceptual basis of QOL for the BMT population. Nursing interventions can improve the QOL for the BMT patient across all phases of the transplant process and long-term issues related to survival. PMID- 1504954 TI - The optimal functioning plan. A key element in cancer rehabilitation. AB - Individuals with cancer should be assisted to achieve optimal levels of functioning before, during, and after cancer treatment. However, to reach optimal functioning a well-defined plan of action is required. This article presents an Optimal Functioning Plan (OFP) aimed at attaining the best possible outcomes for all individuals treated for cancer. The OFP centers on physical functioning, nutritional adequacy, a practical level of independence in activities of daily living, self-care competence, a realistic optimistic outlook, and effective management of side effects. The OFP is a key element of cancer rehabilitation. It represents a way of packaging cancer care in a health-oriented framework. PMID- 1504955 TI - Nursing diagnoses in an oncology population. AB - The purposes of this study are to identify the nursing diagnoses occurring in an oncology population, to validate these using the clinical validation model, and to determine whether clusters of defining characteristics and etiologies occurred among the diagnoses identified. Secondary analysis was conducted using the patient care records of 48 oncology patients. Twenty-five nursing diagnoses were identified. The most common diagnoses were alteration in comfort (pain) and alteration in nutrition (less than body requirements). The etiologies of stress, pain, life changes, disease, and treatment occurred in some combination in 14 diagnoses. The defining characteristics of pain and fatigue/weakness occurred in over six diagnoses. Clusters of defining characteristics occurred with eight diagnoses. Clusters of etiologies occurred with the diagnosis of sleep/rest disturbance. Validation of defining characteristics and etiologies indicated variation from those proposed by the North American Nursing Diagnosis Association. One overriding variation was in the degree of specificity of defining characteristics used in clinical practice. The findings of this study support the need for continued validation of nursing diagnoses and continued education of nurses in the use of nursing diagnoses. The findings also contribute to the body of knowledge in nursing diagnoses in oncology patients, and contribute to the work beginning to be done in the field of nursing diagnosis with research into the existence of clusters of defining characteristics, etiologies, and/or nursing diagnoses. PMID- 1504956 TI - The effects of treatment for cancer on male fertility and sexuality. AB - The sequelae of some treatments for cancer, by virtue of their systemic action, adversely affect three aspects of male sexuality: desire, physical function, and cytokinetic gonadal processes. Other more localized therapies, such as surgery and radiation therapy, may affect only one aspect. Frequently, the effects of cancer therapy are interrelated, thus making it difficult to identify any single problem. This article discusses the impact of medical therapy, including chemotherapy, surgery, radiation therapy, and hormonal manipulation, as they relate to male sexuality. Interventions to promote sexual rehabilitation, either by intensive therapy or nursing actions, are discussed. PMID- 1504957 TI - Comparison of two breast self-examination palpation techniques. AB - In this randomized clinical trial, we compared the vertical strip (VS) and the concentric circle (CC) patterns of breast palpation in order to determine which pattern provided the most thorough self-examination and the best lump detection in breast models. The sample consisted of 34 adult women from a Veterans Outpatient Clinic in the Northwest who were assigned according to breast size (large or small) to one of two groups. Subjects were pretested and randomly taught one method of palpation. Proficiency in the palpation technique, area covered, and number of lumps detected were evaluated. Interrater reliability for proficiency evaluation was 86%. During breast self-examination, the VS group covered significantly more area than the CC group (t = 2.72, p = 0.01). Breast size did not affect breast area covered. Lump detection using breast models did not differ between the two groups. Though this study did not support the conclusion that increased thoroughness leads to increased lump detection, there is support in the literature. Lack of difference in lump detection in this study may have been due to the constraints of the breast models used. However, further research is needed. PMID- 1504958 TI - Distress in cancer patients and primary nurses' empathy skills. AB - This descriptive, correlational study was designed to explore the relationship between the empathy skills of primary nurses and the distress level of their primary patients. Data on empathy skills were generated from the La Monica Empathy Profile. Data on patient distress were generated from the Profile of Mood State Inventory and a Visual Analogue Scale. A nonprobability convenience sample of 65 primary nurses employed on surgical primary nursing care units of a large teaching hospital participated in the study. Sixty-five cancer patients assigned to the participating primary nurses also took part in the study. Descriptive statistics of each variable were examined. Pearson product-moment correlations were used to examine the hypothesis and the demographic variables for nurses and patients. Analysis of variance was used to assess relationships among many of the demographic variables. A significant correlation (but not in the expected direction) was found between the perceiving/feeling/listening empathy skill and patient distress. Nurses' age, years of experience, and education were significantly correlated with some empathy skills. Distress levels of female patients were higher than those of male patients. In general, nurses scored low in the use of empathy skills, and patients scored low in distress. The complex nature of defining and measuring communication skills and relating these skills to outcomes in patient care, such as distress, requires more study. Research questions exploring how and why nurses' interpersonal skills make a difference to patients and their health care outcomes must be generated by nurse administrators, nurse educators, nurse researchers, and practicing nurses. PMID- 1504959 TI - Using diversional activity to enhance coping. AB - Diversional activity deficit, a nursing diagnosis that occurs with prolonged hospital treatment, requires creative and practical ways for nurses to support patients. A tool designed to assess diversional needs is described. Benefits include improved relationships and enhanced patient coping with a minimum of cost and inconvenience. PMID- 1504961 TI - On trials to avoid restenosis after PTCA. PMID- 1504960 TI - Exploration of home care resources for rural families with cancer. AB - The purpose of this qualitative study was to explore the availability and perceived adequacy of formal resources to assist family caregivers of rural persons with cancer. Ten participants who had provided home care for a family member with cancer throughout their illness and death were interviewed in two focus groups. An important finding was that the more rural the family, the more limited and inadequate the formal resources available to assist the family. A second major finding was that the longer the dying trajectory and the greater the deterioration of the person with cancer, the more resources became inadequate and the greater the caregiver burden. PMID- 1504962 TI - [Silent ischemic cardiopathy: a study with dynamic electrocardiogram and ergometric test]. AB - Ninety-two patients with effort angina were retrospectively studied to define the prevalence, the daily distribution and the prognostic value of silent ischemic attacks. All patients had positive Holter monitoring and exercise test; coronary angiography, performed in 75/92 patients, showed 1, 2 or 3-vessels disease. Six hundred ninety-three ischemic episodes, 481 (69.5%) silent and 212 (30.5%) symptomatic, were recorded by Holter monitoring, with the highest incidence in the morning; 74/92 patients (80%) showed silent ischemic attacks. Mean duration of the symptomatic and silent ischemic attacks was respectively 9.8 +/- 5.2 and 6.4 +/- 4.2 min (p less than 0.0001); mean ST-segment depression was respectively 2.8 +/- 1.2 and 2.3 +/- 0.8 mm (p less than 0.0001). During exercise testing 86 patients (93%) had both chest pain and ST-segment changes, 2 patients (2%) only angina and 4 patients (5%) only ST-segment depression. Mean heart rate at onset of ischemia was higher during exercise testing compared with Holter monitoring (119 +/- 20 vs 95 +/- 22 b/min; p less than 0.0001). No significant difference was shown between patients with and without silent ischemia about the prevalence of 1, 2 and 3-vessels disease; 1-year cardiovascular mortality in the 2 groups of patients was respectively 6.8% and 5.5% (p:NS). In patients with effort angina, silent ischemia has not a poor prognostic value; Holter monitoring is very useful to the correct assessment of these patients. PMID- 1504963 TI - [Intraoperative evaluation of tricuspid valve annuloplasty with transesophageal echocardiography]. AB - The present study shows a new application of transesophageal echocardiography (TEE) to optimize tricuspid valve annuloplasty. Eighteen patients with tricuspid regurgitation (TR) underwent De Vega tricuspid annuloplasty. After cardiopulmonary bypass the tension on the suture was adjusted until the surgeon could not feel any regurgitant jet by intraatrial palpation; subsequently, the tension was further adjusted on the basis of TEE. The post-pump residual tricuspid regurgitation was assessed by semiquantitative grading of tricuspid regurgitation (0 to 4+), area of regurgitant jet and percentage of right atrial area subtended by jet area. The data obtained by intraatrial palpation were compared with the data obtained by TEE. A significant reduction of residual tricuspid regurgitation was shown by TEE when compared to intraatrial palpation. After a follow-up period of 2 weeks, no significant changes in the grade of TR were observed. The results showed that the use of TEE was able to optimize the De Vega's tricuspid annuloplasty. PMID- 1504964 TI - [Ambulatory coronary arteriography with 5 French catheters: experience with 604 procedures]. AB - Ambulatory coronary arteriography was carried out in 604 patients, 143 women and 461 men, mean age 53 +/- 14 years. An absolutely stable clinical condition was the main criterion of selection for this investigation and the protocol consisted in day-hospital admission, absence of routine anticoagulation, small calibre (5 French = 1.7 mm diameter) catheters, mobilization 4 hours and discharge 6 hours after the end of the procedure. The percutaneous femoral approach was used in 95% of cases; 56% of patients presented significant single-or multi-vessel coronary artery disease: there were 7 cases of left main coronary artery narrowing; 31 patients required full hospital admission, mainly because of the severity of coronary lesions. Minor complications occurred in 2% of cases. PMID- 1504965 TI - [Color-Doppler echocardiography in electromechanical dissociation. Study of 2 cases]. AB - Electromechanical dissociation (EMD) is a condition of cardiac arrest occurring despite the persistence of apparently effective cardiac electric activity. Secondary EMDs are consequence of catastrophic circulatory failure (i.e. great vessel rupture, massive pulmonary embolism, cardiac tamponade), resulting in sudden and critical changes in hemodynamic load. Primary EMDs, on the other hand, occur in presence of intact circulatory system; they are known to be associated with global cardiac ischemia and contraction failure; however, the exact pathophysiologic change, triggering the onset of primary EMD, is still unknown. The current hypothesis of electromechanical uncoupling (a supposed derangement of excitation and contraction linking) has not been demonstrated. On the contrary, in a previous series of 22 2D-echocardiographic evaluations of patients with EMD, wall and valvular motion was visible in the majority of cases. In our Coronary Care Unit we had the opportunity to perform 2D and color-Doppler echocardiogram in 2 patients, developing primary EMD just while the examination was in course; we subsequently completed the examinations in the short pauses of cardio pulmonary resuscitation. Both patients died and necropsy showed in both cases recent large myocardial infarction, without hemopericardium. The analysis of the echocardiograms emphasized the presence of a residual cardiac mechanical activity: minimal segmental wall motion of left ventricle (LV); residual mitral valve motion, but no visible closure; diastolic low-velocity orthograde transmitralic flow; systolic regurgitant flow from LV to left atrium. On the other hand, we didn't observe any systolic flow directed to the LV outflow tract and to the aorta.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1504966 TI - [Anomalous insertion of the mitral valve. A rare form of subaortic obstruction in children]. AB - Among different anatomical causes of subaortic obstruction, anomalous attachment of the mitral valve on ventricular septum is one of the rarest. We report our experience with 4 such cases of subaortic obstruction. Their age at first observation ranged between 1 and 6 months. All patients had viscero-atrial situs solitus, levocardia and normal atrio-ventricular and ventriculo-arterial connections. None had associated cardiac septal defects. Cases with atrio ventricular canal were excluded. All patients showed a systolic ejection murmur and electrocardiographic features of left ventricular hypertrophy; 3 presented congestive heart failure in the first 3 months of life. Diagnosis was made by 2D echocardiography and cardiac catheterization in 3 patients and intraoperatively in 1. Only in the last 2 patients, correct diagnosis was made at the initial 2D echocardiographic examination. Due to left ventricular hypertrophy, in the first 2 patients hypertrophic obstructive cardiomyopathy was originally suspected. One patient died intraoperatively during attempted transaortic resection of subaortic obstruction. Other 2 patients underwent left ventricle-aortic conduit implantation. Of these 2 patients, 1 died 3 months later for sepsis and the other was reoperated upon 3 years later for mitral valve replacement and conduit take down, with good clinical result. The fourth patient is waiting for surgical intervention. Subaortic obstruction due to anomalous attachment of the mitral valve on ventricular septum may present with early congestive heart failure; the best diagnostic tool is 2D-echocardiography. Left ventricle-aortic conduit may represent a surgical alternative to transaortic resection. PMID- 1504967 TI - Ambulatory electrocardiography: current clinical concepts. PMID- 1504968 TI - Ambulatory (Holter) electrocardiography technology. AB - Ambulatory ECG is an evolutionary cardiovascular discipline with regard to both its clinical applications and technology. With the technologic advances of the past decade, powerful personal computers have expanded the traditional clinical role of ambulatory ECG examination for cardiac arrhythmias to detection of ST segment changes, heart-rate variability, QT interval measurement, and the signal averaged ECG. These expanded clinical applications increase the practicality of a 24-hour ambulatory ECG on an individual cardiac disease patient and make the 24 hour ambulatory ECG one of the most cost-effective cardiovascular diagnostic tests when used properly. The current clinical developments make valid ST-segment detection and quantitation readily available and heart-rate variability an easily applied investigative tool to a wide spectrum of diseases. Automatic QT interval measurements and signal averaging of ambulatory ECG are just technologically emerging and can be expected to develop more in the near future. PMID- 1504969 TI - Ambulatory electrocardiography evaluation of supraventricular tachyarrhythmias and bradyarrhythmias. AB - Long-term ECG recordings are of great value in the diagnosis and management of patients with cardiac arrhythmias. Information from programmed stimulation studies and intracardiac recordings has markedly improved the diagnostic abilities of the person examining the long-term ECG recording. This article discusses how knowledge from intracardiac electrophysiologic studies has resulted in much better recognition of the type and mechanisms of a supraventricular arrhythmia on the Holter record. PMID- 1504970 TI - Evaluating patients with ventricular arrhythmia. Role of the signal-averaged electrocardiogram, exercise test, ambulatory electrocardiogram, and electrophysiologic studies. AB - There are several methods available for the evaluation of patients with ventricular arrhythmia. The most effective approaches, however, involve the use of techniques that provide objective data. These include ambulatory monitoring and exercise testing (a noninvasive approach), and electrophysiologic testing (invasive). The information derived from these two approaches is complementary, and both are important for patient evaluation and management. These methods are useful for establishing the risk of arrhythmia occurrence in certain patient groups and for establishing the effect of antiarrhythmic agents. The signal averaged ECG is of help in establishing risk in some patient groups, but it has no role for evaluating drug therapy. PMID- 1504972 TI - Current concepts of pathophysiology, circadian patterns, and vasoreactive factors associated with myocardial ischemia detected by ambulatory electrocardiography. AB - Transient ST-segment changes during continuous ECG monitoring occur not only in many clinical ischemic syndromes, but also in a proportion of the normal population. The pathophysiology of episodes of ST-segment change that represent transient periods of myocardial ischemia varies according to the underlying disease process, which may include stable coronary artery disease, unstable angina, variant angina, and syndrome X. Patients with stable coronary artery disease have episodes of ischemia as a result of an imbalance between increases in myocardial oxygen demands and changes in coronary blood flow due to physiologic changes in coronary vasomotor tone. Both these factors are subject to a circadian rhythm that results in a preponderance of ischemia in the morning hours. Vasospasm, often beyond the physiologic range, in localized segments of epicardial coronary arteries causes ischemia and ST-segment changes in variant angina, whereas luminal thrombosis with superimposed vasoconstriction is an important cause of continued ischemia in unstable angina. PMID- 1504971 TI - Drug-induced early and late proarrhythmia. AB - Proarrhythmia is the provocation of a new arrhythmia or the exacerbation of a spontaneously occurring arrhythmia due to drug therapy. A drug's toxic effect may occur early after its initiation, and specific definitions have been offered to detect its presence. Primary and secondary forms of proarrhythmia as well as the type of early proarrhythmic events (fatal, serious, and nonserious) have been recognized. More recently, the concept of a late proarrhythmic event (enhanced arrhythmic death) has been defined using placebo-controlled trials. This late proarrhythmic response is extremely important in defining the benefit versus risk ratio that is the key to proper use of drug therapy. PMID- 1504973 TI - Ambulatory electrocardiography evaluation of asymptomatic, unstable, and stable coronary artery disease patients for myocardial ischemia. AB - Transient episodes of myocardial ischemia can be reliably detected by AEM in patients with known CAD. AEM appears to be particularly useful for patients in whom symptom control has been achieved with conventional antianginal drugs because many of these patients (up to 50%) continue to have residual silent ischemia that would otherwise remain undetected. Despite the lack of symptoms, numerous studies in patients with stable and unstable coronary syndromes have shown that the presence of silent ischemia during AEM is associated with an increased risk of subsequent coronary events and cardiac death. Although Holter monitoring is a practical and reliable tool for prolonged evaluation of myocardial ischemia, its routine use can not be advocated until its clinical role has been clearly defined in the ongoing large prospective studies. PMID- 1504974 TI - Ambulatory electrocardiography evaluation of the post-coronary artery bypass graft and post-percutaneous transluminal coronary angioplasty patient. Diagnostic and prognostic value. AB - Investigations carried out in recent years have shown that patients with coronary heart disease display partial to considerable extent transient ST-segment changes that can be determined with ambulatory ECG. An interesting question is how often transient ST-segment changes are present in patients in whom the indication for an aortocoronary bypass operation or percutaneous transluminal coronary angioplasty (PTCA) has already been determined. In the patients who are waiting for a bypass operation or PTCA, the proof of myocardial ischemia has been determined, and which subgroups of patients display ST changes in the ambulatory ECG must be tested. It is interesting to ask what happens to such transient ischemic episodes as a result of surgical or catheter intervention, how often such episodes are present even after these interventions, and whether the latter has a clinical significance in view of the success of the intervention (graft patency in coronary artery bypass graft patients or reocclusion in PTCA patients). Furthermore, it is to be tested whether transient ST-segment changes take on a prognostic significance in the long-term follow-up after bypass operation or PTCA. PMID- 1504975 TI - Do silent myocardial ischemia and ventricular arrhythmias interact to result in sudden death? AB - The relationship between silent myocardial ischemia and sudden death depends on the severity and duration of the ischemia. Severe, transmural and persistent ischemia, as occurs in myocardial infarction, can trigger sudden death. When the ischemia is severe and transmural but not long-standing (e.g., Prinzmetal angina), ventricular arrhythmias appear frequently, but they are rarely malignant. In cases of subendocardial ischemia, there is no definitive proof of this relationship. PMID- 1504976 TI - Complementary role of ambulatory electrocardiographic monitoring and exercise testing in evaluation of myocardial ischemia. AB - For detection of myocardial ischemia, exercise testing is a better tool than AEM and therefore should be preferred procedure for this purpose. In patients who exhibit ischemic changes on exercise testing, the presence of ischemic changes on AEM carries significant prognostic information beyond the results of exercise testing; therefore, it is recommended that this test be performed in those who have ischemic changes on exercise at a moderate or low workload. AEM together with exercise testing can be used to assess efficacy of anti-ischemic drugs, can help to define the underlying mechanism of ischemia during daily life, and in certain groups of patients, like those with unstable angina, peripheral vascular disease, or after cerebrovascular events, it can replace exercise testing as a method for detecting ischemic changes. PMID- 1504977 TI - The role of ambulatory monitoring in assessing cardiac risk in peripheral vascular surgery. AB - Patients undergoing vascular surgery have a uniformly higher risk for postoperative cardiac events, and this risk has traditionally been difficult to quantify. Research has focused on the addition of noninvasive testing to the preoperative assessment of patients at moderate risk by clinical criteria. Current data suggest that preoperative ambulatory monitoring successfully identifies risk for cardiac events in patients undergoing vascular surgery and represents a practical alternative, particularly when patients cannot exercise. Postoperative monitoring appears to be particularly useful in heralding cardiac events in high-risk patients with enough lead time to make prophylactic and preemptive intervention feasible. PMID- 1504978 TI - Myocardial dysfunction in silent myocardial ischemia as demonstrated by ambulatory radionuclide left ventricular function studies. AB - Until recently, it has not been possible to combine both ambulatory electrocardiographic monitoring, monitoring and ambulatory left ventricular function monitoring, but new developments have helped solve this problem. A technique based on the nuclear probe was introduced in the early 1980s to allow continuous recording of left ventricular volumes and ejection fraction over a 4 to 6 hour period during ambulatory activities following a single injection of radioisotope; the device was termed the VEST. In addition to validation studies, left ventricular function during ambulatory activities of various types has been measured with the VEST, and there are now several reports that document reduction in left ventricular ejection fraction in patients with coronary artery disease. These episodes meet the criteria for silent ischemia: objective evidence of myocardial ischemia in the absence of angina or anginal equivalents. Thus, patients with coronary artery disease can be followed for hemodynamic evidence of myocardial ischemia (even when they are not aware of the episodes) and results of therapy better monitored than by the ambulatory ECG alone. PMID- 1504979 TI - Efficacy of therapeutic interventions for silent myocardial ischemia and clinical trial benefit. AB - This article reviews the efficacy of medical and revascularization therapeutic interventions directed at the reduction or elimination of silent myocardial The review focuses on the use of standard anti-ischemic medications, including nitrates, calcium antagonists, and beta-blockers. In addition, data suggesting therapeutic benefit of antiplatelet agents are discussed. Finally, the results of studies evaluating the efficacy of revascularization with PTCA and coronary artery bypass graft surgery are reviewed. PMID- 1504980 TI - Time domain measurements of heart rate variability. AB - Assessment of HRV through time domain variables is a simple and practical method of assessing autonomic function. In this capacity its utility has been demonstrated in normal subjects and in diverse cardiac and noncardiac pathologic states. It can be used to assess the effects of drugs and other interventions, including exercise and psychological and physical stress on cardiac autonomic tone. Importantly, decreased HRV is almost uniformly associated with adverse outcome. The prognostic information appears to incorporate both alterations in autonomic tone and longer term components and is best assessed using ambulatory ECG recordings. Defining the clinical applicability and physiologic mechanisms of changes in HRV remain active areas of research. PMID- 1504981 TI - Heart rate variability. Frequency domain analysis. AB - Experience with frequency domain analysis over the past two decades strongly suggests that it represents a unique, noninvasive tool for achieving a more precise assessment of autonomic function in both the experimental and clinical settings. Available studies indicate that the significance of the HF component is far better understood than that of the lower frequency components. In general, it is considered to reflect vagal activity, and because it is readily manipulated pharmacologically, is used as a an index of that activity. However, some caution is required because this parameter also is strongly influenced by the degree of coupling between respiration and heart rate, which, in turn, reflects the intensity of the respiratory effort as well as of parasympathetic activity. Respiratory pattern also can significantly influence HF power. The use of controlled breathing minimizes these problems, improves reproducibility of test findings, and also facilitates quantitative comparisons. The situation with respect to LF power is more complicated because it is modulated by both sympathetic and parasympathetic outflows (see previous discussion) as well as by other factors, including baroreceptor activity. Therefore, LF analysis per se cannot afford a precise delineation of the state of sympathetic activation. Determinations of the LF/HF ratio, an index of sympathovagal balance both under control conditions and in conjunction with interventions that maximize sympathetic and parasympathetic activity, provide additional insights, as do correlations between spectral activity and direct nerve recordings, plasma norepinephrine concentrations, and radionuclide imaging of adrenergic nerves. Renewed interest has recently been evinced in frequencies lower than 0.04 Hz in view of reports that the VLF portion of the spectrum (0.01-0.04 Hz) reflects a purer form of sympathetic activity than does the LF band. Despite the potential applicability to clinical problems, only very little is known about the physiologic basis of the VLF and ULF bands. Further study is required. However, it is important to note that meaningful determinations of VLF and ULF power may be difficult because decreases in frequency to such low levels are associated with an increasing propensity to violate the rules governing power spectral determinations (see previous discussion and appendix), violations that diminish reliability despite the most sophisticated preprocessing. It is also noteworthy that the reliability of spectral power determinations diminishes with decreases in the power of the signal and of the signal-to-noise ratio.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1504982 TI - Ambulatory electrocardiography signal averaging. Practicalities, clinical value, and potential applications. AB - Ability to perform high-resolution ECG from Holter tapes would significantly increase the utility of ambulatory monitoring as a screening tool for detecting the risk of serious ventricular arrhythmias without the cost and inconvenience of making a separate real-time recording. Despite some theoretical objections focusing on the relatively poor high-frequency response of Holter systems, it has nevertheless been shown to be both reasonable and practical to use them for late potential analysis. Technical issues, history, clinical results, and bibliography are presented in reviewing the current status of this emergent technique that shows promise for combining two techniques already shown to have independent diagnostic and prognostic value. PMID- 1504983 TI - Appropriate indications for ambulatory electrocardiographic monitoring. A clinical perspective. AB - This article summarizes the clinical indications for ambulatory monitoring using current information from the Cardiac Arrhythmia Suppression Trial and utility of the procedure to detect both drug efficacy and proarrhythmia. It also discusses silent ischemia detection and heart rate variability as an indicator of autonomic tone. PMID- 1504984 TI - Factors related to spouses' quality of life 1 year after coronary artery bypass graft surgery. PMID- 1504985 TI - [Medical ethics--an independent medical specialty]. AB - Medical ethics as a discipline was not taught systematically since 1952. Some ethical problems were, however, solved; the author presents therefore the history of medical ethics and reasons for and circumstances under which the Institute of Medical Ethics was created at the Third Medical Faculty in Prague. Workers of the mentioned department (H. Haskovcova, V. Spalek, J. Simek) after presentation of an expose became the initiators of the new independent discipline. The text of the expose is submitted in extenso. Since 1991 medical ethics are an independent medical discipline in the Czech Republic and lectures on the subject are part of the curriculum of medical students. PMID- 1504986 TI - [Use of flow cytometry in the diagnosis of acute leukemias in childhood]. AB - The authors examined, using the method of flow cytometry, 56 children with acute lymphoblastic leukaemia. Leukaemic cells of the bone marrow aspirate and peripheral blood were examined on a FACS 440 apparatus for establishment of the diagnosis before treatment was initiated. Individual immunological subtypes were differentiated by means of a panel of monoclonal antibodies. 80.5% of acute lymphoblastic leukaemias originated from different developmental stages of B cells, 12.5% were formed by leukaemias from T cells and 7% were non differentiated leukaemias. The mean follow-up period in the group was 33 months. According to the therapeutic results children with leukaemia ensuing from precursors of B cells had a more favourable prognosis than children with T leukaemia and children with non-differentiated leukaemia. Quantitative examination of nuclear DNA of leukaemic cells revealed in 55% of the patients of the group aneuploidy with clear predominance of hyperdiploidy, 45% of the patients suffered from diploidy. The least number of relapses was recorded in the investigation period in children with hyperploid acute lymphoblastic leukaemia. The proliferating activity of leukaemic blasts was expressed by the number of cells in the S + G2M stage of the cellular cycle and was higher in the bone marrow than in peripheral blood but did not differ in individual immunological subtypes or in diploid leukaemias. The authors were not able to prove its prognostic importance. Flow cytometry is a rapid and sensitive diagnostic method which makes it possible to characterize more satisfactorily the heterogeneous group of acute lymphoblastic leukaemias. PMID- 1504987 TI - [Personal experience with detection of antibodies against neutrophil cytoplasm]. AB - Detection of antibodies against components of neutrophil cytoplasm (ANCA) is of diagnostic value in Wegener's granulomatosis and in some other types of vasculitis. In the submitted paper the authors discuss methodical aspects of ANCA detection. The most frequently used method for assessment of ANCA is indirect immunofluorescence, at present it is possible to use also the ELISA method. Based on their own group of patients the authors discuss the association of ANCA with various types of diseases and the importance of assessing ANCA during monitoring of immunosuppressive treatment. PMID- 1504988 TI - [Antibodies against neutrophil cytoplasm. A new group of autoantibodies]. AB - Antibodies against cytoplasmic antigens of neutrophils are a recently described group of autoantibodies associated with some types of primary systemic vasculitis and necrotizing glomerulonephritis. In clinical practice they are a useful laboratory examination which helps with the diagnosis of this group of diseases and to follow up their activity and response to treatment. The existence of ANCA implies also a new aspect of classification of vasculitis. The autoimmune reaction of ANCA with lysosomal enzymes is also another possible mechanism of development of tissue damage. The submitted paper is a review of literature on the importance of ANCA from the practical as well as theoretical aspect. PMID- 1504990 TI - [Report on the Internal Grant Agency at the Czech Ministry of Health]. PMID- 1504989 TI - [Jan Brod and Czechoslovak cardiology. On his unattained 80th birthday. 19 May 1912-10 February 1985]. PMID- 1504991 TI - [Patients' rights in the Czech Republic]. AB - The ethical code, the so-called Patients' rights, was published on February 25, 1992 and applies in Bohemia and Moravia. The initiative in this matter was taken by the Central ethical commission of the Ministry of Health of the Czech Republic. The latter commission prepared a draft of the Czech version and after comments supplemented the text approved and proclaimed it. In the submitted paper the text of the document is presented in extenso and the author explains the history of patients' rights in Europe. PMID- 1504992 TI - [EDRF-NO. The endothelium-derived relaxing factor is nitric oxide]. AB - The author reviews findings assembled during the last 20 years on the endothelium derived relaxing factor (EDRF), and in particular findings assembled the last five years which revealed that EDRF is identical with nitric oxide, NO. The enzyme NO synthetase produces NO from l-arginine with the concurrent formation of citrulline and is present not only in the endothelium of the vascular wall but also in cerebral neurons and other tissues. NO is probably also the effective factor of the vasodilatating action of organic nitrates (nitroglycerol, amyl nitrite, sodium nitroprusside). In recent years these findings are applied also in clinical work. In atherosclerosis of the coronary vessels NO formation is obviously reduced and l-arginine infusion may improve the coronary blood supply in patients with hypercholesterolaemia. Inhalation of NO has been tried in pulmonary hypertension. Antidotes of NO (methylene blue) conversely may prevent hypotension in hepatic failure. Infusion of an antidote of l arginine prevents hypotension in septic shock. This is due to the fact that an excess of NO is formed from macrophages during infections. NO is, however, also mutagenic and there are reports on its participation in the genesis of genetic and neoplastic diseases. PMID- 1504993 TI - [Sonographic findings in Crohn's disease]. AB - In 59 subjects (25 men and 34 women) with confirmed Crohn's disease 91 sonographic examinations were made, using dynamic records by means of a sector probe with a frequency of 3.5 and 5 MHz. The disease had persisted on average for 7.1 years. A positive sonographic finding was recorded in 68% of the examined subjects, incl. 42% where the finding on palpation of the abdominal cavity was negative. During examination the following typical findings were recorded: the symptom of a tubular structure with a thickened intestinal wall (frequency 77.5%), cockade symptom (65%), convolution of the loops (62.5%), congestion in the intestinal loops (10%) and abscess in the abdominal cavity (7.5%). Ultrasonography is a significant diagnostic method which can help in the differential diagnosis of resistance on palpation and in the follow up of the disease and the effect of therapy in patients with Crohn's disease. PMID- 1504994 TI - [Long-term home parenteral nutrition using a totally implanted cannulation system]. AB - A 29-year-old patient suffering from stenosis of the rectum and a periproctal fistula due to a severe form of Crohn's disease was completely fed by the parenteral route for 15 months, incl. 13 months at home, via a totally implanted cannula system Implantofix, Braun Co.. The patient felt throughout the period of parenteral nutrition very well, he worked and the secretion from the fistula stopped after four weeks. After 15 months of complete parenteral nutrition and elimination of oral food intake a marked improvement of the local finding in the rectum was observed. All laboratory findings (haemogram, liver tests, urea, creatinine, transferrin, albumin, cholinesterase and pre-albumin, serum levels of sodium, potassium, chlorides, calcium and phosphates) were throughout the observation period within a normal range. The body weight of the patient increased during the 15 months by 1 kg. The described case is the first one where domiciliary parenteral nutrition was used in Czechoslovakia under ambulatory conditions. PMID- 1504995 TI - [Favorable effect of methylprednisolone pulse therapy in dysphagia and primary idiopathic polymyositis/dermatomyositis]. AB - In five previously not treated patients with active primary idiopathic polymyositis/dermatomyositis and severe dysphagia persisting for 3-8 weeks treatment with a series of 4-5 intravenous pulses a 1 g methylprednisolone was provided. In four patients dysphagia disappeared within 2-14 days, in one patient within 30 days marked improvement was recorded. During the 12-64-month follow up period in none of the patients relapse or deterioration of dysphagia was observed. One female patient died 12 months after establishment of the diagnosis during reactivation of the basic disease with marked fibrosis of the pulmonary interstitium, the remaining patients are in permanent remission. PMID- 1504996 TI - [Actinomycosis of the ovary as a cause of cachexia in a young patient]. AB - The authors describe the case of a 40-year-old female patient treated for prolonged periods unsuccessfully with several antibiotics on account of a febrile condition of obscure aetiology and subsequently repeatedly subjected to laparotomy on account of intra-abdominal abscesses. The cause of the fever, abdominal pain and gradual cachectization was an abdominal form of actinomycosis. After establishment of the diagnosis the patient was successfully treated by long term penicillin administration and recovered completely. The authors discuss experience reported in the literature and therapeutic possibilities in actinomycosis. PMID- 1504997 TI - [Medical support for the American troops in the Persian Gulf]. PMID- 1504999 TI - Current bibliography of cell calcium prepared by the University of Sheffield Biomedical Information Service. PMID- 1504998 TI - [The history of Czechoslovak medical boards]. PMID- 1505000 TI - New developments in the calmodulin field. PMID- 1505001 TI - Calcium and calmodulin. AB - A description of the value of calcium and calmodulin is given in terms of their dynamics and structures. It is insisted that a full appreciation of their value demands recognition of the time domain, motion, in evolution in concert with structure. Only in this way can homeostasis of resting states as well as triggering, assisted by calcium/calmodulin, be described. The best analogy is with a regulatory electrical control such as household central heating system where calcium carries the current and calmodulin triggers the heating (cellular work) and the pumps (cellular pumps). There is full feed-back control. PMID- 1505002 TI - The linker of calmodulin--to helix or not to helix. AB - The linker regions of the central helices of calmodulin and of troponin C are observed to be alpha-helices in crystal and in solution. However, these linkers are predicted to be non-helical by standard algorithms. Further, there is strong evidence that when calmodulin interacts with some of its targets this linker helix bends. The linker appears to be delicately balanced between helical and non helical conformations. A review of this subject suggests that one can anticipate more unpredicted conformations for the central helices of the score of other proteins that have four EF-hand domains. PMID- 1505003 TI - The solution structures of calmodulin and its complexes with synthetic peptides based on target enzyme binding domains. AB - Small-angle X-ray and neutron scattering experiments have given important information on the solution structures of calmodulin and its complexes with synthetic peptides used to model target enzyme interactions. In combination with crystallographic data, site directed mutagenesis and various spectroscopic studies, these experiments have contributed to our understanding of the solution structure of calmodulin in different functional states. We have gained important insights into the conformational flexibility in calmodulin that appears to be crucial to its regulatory functions. Specifically, flexibility in the interconnecting helix region of calmodulin has been shown to play a critical role in facilitating calmodulin's binding to a wide variety of target enzymes whose activities are thus regulated. This review will focus mainly on the contributions small-angle scattering has made to our understanding of the solution structure of calmodulin in the context of other studies, with particular regard to circular dichroism and Fourier transform infrared studies that complement the small-angle scattering data. PMID- 1505005 TI - Mutational analysis of calmodulin in Saccharomyces cerevisiae. AB - Calmodulin is well characterized as an intracellular Ca2+ receptor in nonproliferating tissues such as muscle and brain. Several observations indicate that calmodulin is also required for cellular growth and division. Deletion of the calmodulin gene is a lethal mutation in Saccharomyces cerevisiae, Schizosaccharomyces pombe and Aspergillus nidulans. Expression of calmodulin antisense RNA in mouse C127 cells causes a transient arrest at G1 and metaphase. Although these results indicate calmodulin plays a critical function during proliferation, they do not reveal the function. S. cerevisiae offers an excellent system for identifying calmodulin functions. Because calmodulin mutants can be readily constructed by gene replacement the consequences of mutations in calmodulin can be directly examined in vivo without interference from wild-type calmodulin. The available wealth of information concerning all aspects of the yeast life cycle provides a large framework for interpretation of new results. The recent dissection of cell cycle regulation is just the latest example of the important insights provided by analyzing basic cellular processes in yeast. Whether studies of calmodulin in yeast will reveal a universal function is unknown. One encouraging result is that yeast cells relying on vertebrate calmodulin as their only source of calmodulin survive and grow well, even if the amount of vertebrate calmodulin is equivalent to the normal steady state levels of yeast calmodulin. This review discusses the varied techniques we are using to identify the functions of calmodulin in yeast. As part of the analysis, we are defining the essential elements of calmodulin structure. PMID- 1505004 TI - Solution structure of calmodulin and its complex with a myosin light chain kinase fragment. AB - The solution structure of Ca2+ ligated calmodulin and of its complex with a 26 residue peptide fragment of skeletal muscle myosin light chain kinase (skMLCK) have been investigated by multi-dimensional NMR. In the absence of peptide, the two globular domains of calmodulin adopt the same structure as observed in the crystalline form. The so-called 'central helix' which is observed in the crystalline state is disrupted in solution. 15N relaxation studies show that residues Asp78 through Ser81, located near the middle of this 'central helix', form a very flexible link between the two globular domains. In the presence of skMLCK target peptide, the peptide-protein complex adopts a globular ellipsoidal shape. The helical peptide is located in a hydrophobic channel that goes through the center of the complex and makes an angle of approximately 45 degrees with the long axis of the ellipsoid. PMID- 1505006 TI - Yeast calmodulin: structural and functional elements essential for the cell cycle. AB - The budding yeast Saccharomyces cerevisiae is a suitable organism for studying calmodulin function in cell proliferation. Genetic studies in yeast demonstrate that vertebrate calmodulin can functionally replace yeast calmodulin. In addition, expression of half of the yeast calmodulin molecule is found to be sufficient for cell growth. Characterization of conditional-lethal mutants of yeast calmodulin as well as the intracellular distribution of calmodulin have suggested that at least two cell cycle steps require calmodulin function. One is nuclear division and the other is the maintenance of cell polarity. A current focus is to understand which kinds of target proteins are involved in mediating the essential functions of yeast calmodulin in these processes. Thus far, three yeast enzymes whose activity is regulated by calmodulin have been identified. PMID- 1505007 TI - Regulation of expression of calmodulin and calmodulin-related genes by environmental stimuli in plants. AB - Plants are very sensitive to environmental stimuli and have evolved the ability to adapt to many environmental stresses by altering development. In particular, mechanical stimuli such as touch or wind, result in growth changes that result in plants with greater resistance to such mechanical stimuli. We have initiated a molecular dissection of the pathways that enable perception of and responses to these environmental stimuli in plants. We have discovered five genes--termed the TCH genes--whose expression levels are strongly and rapidly increased in response to stimuli such as touch, wind, rain, wounding and darkness. Three of the TCH genes encode proteins related to calmodulin thereby implicating roles for calcium ions and calmodulin in the transduction of signals from the environment. PMID- 1505008 TI - Molecular pharmacology of calmodulin pathways in the cell functions. AB - In this paper we summarize much of the pharmacological evidence that has led to our current understanding of calmodulin-regulated cell function, with emphasis on aspects that may be relevant to drug design. These newly developed compounds are one of the most powerful tools as molecular probes for pharmacological approach, and will shed light on the physiological significance and molecular mechanisms of calmodulin-dependent pathways in various cell functions. PMID- 1505009 TI - Male fertility regulation: a study on acceptance among men in Zimbabwe. AB - Both traditional and modern methods of family planning widely practised currently in most countries, especially in sub-Saharan Africa, focus solely on the woman. There is hardly data on male directed methods of fertility regulation, or indeed whether, or not, such contraceptive options are acceptable. Contraception, whether for spacing, avoiding unintended pregnancy or limiting family size, is almost always a female prerogative. This, in certain circumstances, is despite the available female method being contraindicated. Acceptance of male sterilisation (vasectomy), condom use and male contraceptive pill were investigated in a representative sample of 711 Zimbabwean men. Only 14 pc of men considered vasectomy an acceptable method of contraception and none of the men had current or previous use of this method. Seventeen percent of the men had prompted knowledge of this method, compared to 53 pc who had prompted knowledge of female sterilisation. Only six percent of respondents reported current use of condoms and amongst condom non-users, 58.9 pc would not use the method if asked by a wife or partner. Surprisingly, 31.7 pc of the male respondents reported that they would consider a male contraceptive pill or injection if available. Should husband want no more children, 42.2 pc of men said they would agree to wife sterilisation and 19.5 pc could consider vasectomy. Previous use of condoms was reported by 33.8 pc of the men. Eighty eight (88 pc) percent of respondents had some formal education, although acceptance rates decreased with less education and older ages. Circumstances during which a male method could be considered, reasons and socio-economic determinants for acceptance of male fertility regulatory methods are discussed.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1505010 TI - Drug prescribing in paediatric in-patients at Harare and Parirenyatwa Central Hospitals. AB - Two-hundred-and-fifty records were examined at Harare and 250 at Parirenyatwa Central Hospitals over a six-month period to investigate drug prescribing patterns for paediatric in-patients. The majority of the patients were between one to three years and weight 6 to 7.9 kg. A total of 1,725 prescriptions were received by these patients with an average of 3.45 (range = 0-18 drugs) per patient. The most frequently used pharmacological groups at both hospitals were anti-infectives (51 pc), intravenous fluids and supplements (22 pc) and analgesics (10.6 pc). Benzylpenicillin accounted for 14.6 pc at Harare and 12.9 pc at Parirenyatwa hospital of the anti-infectives respectively. Infections (49 pc) and gastro-enteritis (11.5 pc) were the main diagnoses in all age groups at both hospitals. Respiratory tract infections accounted for 13.5 pc at Harare and 15.2 pc at Parirenyatwa hospital respectively. There was a rational correlation between prevalent diagnosis and drugs used. PMID- 1505012 TI - Current prevalence and some clinical associations of childhood anaemia in urban and rural communities of central Nigeria. AB - The current prevalence of anaemia was determined among children in the age group half to fourteen years in one urban and two rural communities in the middle belt region of Nigeria. A total of 1,775 apparently healthy and 660 sick children were investigated using capillary packed cell volume, PCV, as the diagnostic index. Packed cell volume of healthy children was found to vary between 23 pc and 48 pc. The mean PCV for the whole group was 35.90 pc but the relatively better economic and educational status of urban elite children was reflected in the higher PCV levels. Using the WHO recommended cut-off values for anaemia in children, prevalence of anaemia in the healthy children study was found to be 35.8 pc. When compared with figures recorded in Nigerian children in earlier studies, this finding represents a deterioration and occurs at a time of declining national economy. There were significant differences between groups when classified by age and socio-economic status, with the highest prevalence of 55 pc being found in the rural school-age group and the lowest of 20 pc in the economically better-off urban pre-school children. The overall prevalence of anaemia among sick children was 55 pc with the school age group having the worst value of 70 pc. In most cases, the anaemia was associated with nutritional and infectious conditions. PMID- 1505011 TI - Immunisation and nutritional status of under-fives in rural Zambia. PMID- 1505013 TI - Hysterectomy in the rural tropics. AB - A retrospective study of hysterectomy at a rural hospital in Ghana revealed a high incidence of emergency cases. Uterine fibroids were the commonest indication for elective hysterectomy, followed by surgery for suspected cervical carcinoma. Most emergency hysterectomies were performed because of uterine rupture. The difficulties of managing these problems against the background of the diagnostic and therapeutic facilities available are discussed. PMID- 1505014 TI - Flexor tendon injuries: the result of primary management: a retrospective review of 50 cases treated at Whiston Hospital, England. AB - A retrospective review of 50 cases treated over a 12-month period with 95 tendon injuries was carried out. Post-operative management utilising a modified Kleinert method was used for cases over eight years of age, while those under eight were immobilised in plaster cast. Our results after a mean follow up period of 14 weeks compared well with other series using the Kleinert method. Zone II injuries gave an unexpected better results than those in other zones. PMID- 1505015 TI - Biosocial factors affecting menarche in a mixed Nigerian population. AB - A prospective study of school girls in a mixed Nigerian population revealed that the mean menarcheal age was 13.98 +/- 1.30 years. The mean menarcheal age was influenced by the social class of the parents, being higher in the lower social class, there were considerable variations in the biologic measurements (height, weight and body mass index) among girls who attained menarche. PMID- 1505016 TI - Anatomical sex conversion in a 21-year-old--case report and review of literature. AB - A case of anatomical sex conversion in a 21-year-old genotypic male Nigerian with ambiguous genitalia but who was reared as a girl is presented. The clinical features observed in this particular case and the result obtained after surgery, adjuvant hormone therapy and supportive psychotherapy are discussed. The relevant literature pertaining to the clinical entity is reviewed. PMID- 1505017 TI - Human immunodeficiency virus and Guillain 'Barre' syndrome in intensive care unit patients. AB - Among 155 medical admissions to the intensive care unit during the period 1989 to 1990, 16 patients had Guillain-'Barre' Syndrome (GBS), five of whom were HIV positive. Out of the five cases, three had manifested herpes zoster and one had TB. The impact of HIV infection o GBS is discussed. PMID- 1505018 TI - AIDS in the 1990s--meeting the challenge. PMID- 1505019 TI - p53 function and dysfunction. PMID- 1505020 TI - Anterior pituitary development: short tales from dwarf mice. PMID- 1505021 TI - Are fusion peptides really "sided" insertional helices? PMID- 1505022 TI - Green yeast. PMID- 1505023 TI - A cDNA that suppresses MPP+ toxicity encodes a vesicular amine transporter. AB - Classical neurotransmitters are transported into synaptic vesicles so that their release can be regulated by neural activity. In addition, the vesicular transport of biogenic amines modulates susceptibility to N-methyl-4-phenylpyridinium (MPP+), the active metabolite of the neurotoxin N-methyl-1,2,3,6 tetrahydropyridine that produces a model of Parkinson's disease. Taking advantage of selection in MPP+, we have used gene transfer followed by plasmid rescue to identify a cDNA clone that encodes a vesicular amine transporter. The sequence predicts a novel mammalian protein with 12 transmembrane domains and homology to a class of bacterial drug resistance transporters. We have detected messenger RNA transcripts for this transporter only in the adrenal gland. Monoamine cell populations in the brain stem express a distinct but highly related protein. PMID- 1505024 TI - Connectin: a homophilic cell adhesion molecule expressed on a subset of muscles and the motoneurons that innervate them in Drosophila. AB - Each abdominal hemisegment in the Drosophila embryo contains a stereotyped array of 30 muscles, each specifically innervated by one or a few motoneurons. We screened 11,000 enhancer trap lines, isolated several expressing beta galactosidase in small subsets of muscle fibers prior to innervation, and identified two of these as inserts in connectin and Toll, members of the leucine rich repeat gene family. Connectin contains a signal sequence, ten leucine-rich repeats, and a putative phosphatidylinositol membrane linkage; in S2 cells, connectin can mediate homophilic cell adhesion. Connectin is expressed on the surface of eight muscles, the motoneurons that innervate them, and several glial cells along the pathways leading to them. During synapse formation, the protein localizes to synaptic sites; afterward, it largely disappears. Thus, connectin is a novel cell adhesion molecule whose expression suggests a role in target recognition. PMID- 1505025 TI - Genetic evidence for the involvement of the lck tyrosine kinase in signal transduction through the T cell antigen receptor. AB - Signaling through the T cell antigen receptor (TCR) results both in rapid increases in tyrosine phosphorylation on a number of proteins and in the activation of the phosphatidylinositol pathway. It is not clear how stimulation of the TCR leads to these signaling events. Mutants of the Jurkat T cell line have been previously isolated that fail to show increases in calcium following receptor stimulation. Analysis of one of these mutants, JCaM1, which is defective in the induction of tyrosine phosphorylation, revealed a defect in the expression of functional lck tyrosine kinase. The lack of lck activity was caused in part by a splicing defect. Expression of the lck cDNA in JCaM1 restores the ability of the cell to respond to TCR stimulation. These results indicate that lck is required for normal signal transduction through the TCR. PMID- 1505026 TI - The growth arrest-specific gene, gas1, is involved in growth suppression. AB - This report describes the structure of the mRNA, the protein product, and the growth-regulating activity of one of the growth arrest-specific genes, gas1. From the predicted amino acid sequence, in vitro translation of gas1 mRNA, and immunofluorescence of cells in culture, it appears that the gas1 protein is an integral plasma membrane protein whose expression is linked to growth arrest. When gas1 is overexpressed from a constitutive promoter in quiescent cells, the serum-induced transition from the G0 to the S phase of the cell cycle is inhibited without affecting the normal early serum response. Ectopic expression of the gas1 gene by microinjection in normal and transformed NIH 3T3 cell lines with the notable exception of SV40-transformed 3T3 cells leads to inhibition of DNA synthesis. Thus, gas1 appears to be one component of a negative circuit that governs growth suppression. Its effect is, however, abolished in SV40-transformed cells. PMID- 1505027 TI - Negative control of photoreceptor development in Drosophila by the product of the yan gene, an ETS domain protein. AB - Loss-of-function mutations in the yan gene result in the differentiation of supernumerary photoreceptors in the Drosophila eye. The yan gene encodes a protein with an ETS DNA-binding domain that accumulates in the nuclei of undifferentiated cells during the early stages of eye development. Our data suggest that yan functions as a cell-autonomous negative regulator of photoreceptor development; in the presumptive R7 and cone cells, yan appears to act antagonistically to the proneural signal mediated by sevenless and Ras1. PMID- 1505028 TI - A tissue-specific MAR/SAR DNA-binding protein with unusual binding site recognition. AB - A human cDNA was cloned that encodes a DNA-binding protein (SATB1) that is expressed predominantly in thymus and binds selectively to the nuclear matrix/scaffold-associating DNAs (MARs/SARs). Missing nucleoside experiments showed that SATB1 selectively binds in a special AT-rich sequence context where one strand consists of mixed A's, T's, and C's, excluding G's (ATC sequences). When this feature is destroyed by mutation, SATB1 binding is greatly reduced even if the direct contact sequence remains intact. Conjunctional SATB1-binding sequences become stably unpaired in supercoiled DNA. Specific mutations that diminish the unwinding potential greatly reduce SATB1 binding. However, SATB1 does not bind single-stranded DNA. Chemical interference assays show that SATB1 binds along the minor groove with very little contact with the bases. This suggests that SATB1 recognizes the ATC sequence indirectly through the altered sugar-phosphate backbone structure present in the double-stranded DNA. PMID- 1505029 TI - Autoregulation of the yeast lysyl-tRNA synthetase gene GCD5/KRS1 by translational and transcriptional control mechanisms. AB - We cloned the GCD5 gene of S. cerevisiae and found it to be identical to KRS1, which encodes lysyl-tRNA synthetase (LysRS). The mutation gcd5-1 changes a conserved residue in the putative lysine-binding domain of LysRS. This leads to a defect in lysine binding and, consequently, to reduced charging of tRNA(Lys). Mutant gcd5-1 cells compensate for the defect in LysRS by increasing GCN4 expression at the translational level. GCN4 protein in turn stimulates transcription of GCD5, leading to increased LysRS activity. We propose an autoregulatory model in which uncharged tRNA(Lys) stimulates the protein kinase GCN2, a translational activator of GCN4, and thereby increases transcription of GCD5 and other genes regulated by GCN4. PMID- 1505030 TI - Recombination between similar but not identical DNA sequences during yeast transformation occurs within short stretches of identity. AB - Interactions between similar but not identical (homeologous) DNA sequences play an important biological role in the evolution of genes and genomes. To gain insight into the underlying molecular mechanism(s) of genetic recombination, we have studied inter- and intramolecular homeologous recombination in S. cerevisiae during transformation. We found that homeologous DNAs recombine efficiently. Hybrid sequences were obtained between two mammalian cytochrome P450 cDNAs, sharing 73% identity, and between the yeast ARG4 gene and its human homeologous cDNA, sharing 52% identity. Sequencing data showed that the preferred recombination events are those corresponding to the overall alignment of the DNA sequences and that the junctions are within stretches of identity of variable length (2-21 nt). We suggest that these events occur by a conventional homologous recombination mechanism. PMID- 1505031 TI - A new mechanism of transcriptional regulation: release of an activator triggered by small molecule binding. AB - The FadR protein of E. coli activates transcription of the fabA gene, a key enzyme of fatty acid synthesis. We report that FadR binds to a DNA sequence positioned at -40 relative to the start site of the FadR-regulated fabA transcript (the location favored by positive activators). This binding was found to be specifically antagonized by long chain acyl-CoAs. The chain length specificity of the disassociation of the FadR-DNA complex by acyl-CoAs observed in vitro reflects that seen in the repression of fabA transcription observed upon addition of fatty acids to bacterial cultures. Acyl-CoA antagonism of FadR-DNA interactions is readily reversible. These data indicate that repression of fabA transcription by fatty acids is the first reported example of a repression system mediated by positive control. PMID- 1505032 TI - Integration of human alpha-satellite DNA into simian chromosomes: centromere protein binding and disruption of normal chromosome segregation. AB - Centromeres of mammalian and other complex eukaryotic chromosomes are dominated by one or more classes of satellite DNA. To test the hypothesis that alpha satellite DNA, the major centromeric satellite of primate chromosomes, is involved in centromere structure and/or function, human alpha-satellite DNA was introduced into African green monkey (AGM) cells. Centromere protein binding was apparent at the sites of integrated human alpha-satellite DNA. In the presence of an AGM centromere on the same chromosome, human alpha-satellite was associated with bridges between the separating sets of chromatids at anaphase and an increased number of lagging chromosomes at metaphase, both features consistent with the integrated alpha-satellite disrupting normal chromosome segregation. These experiments suggest that alpha-satellite DNA provides the primary sequence information for centromere protein binding and for at least some functional aspect(s) of a mammalian centromere, playing a role either in kinetochore formation or in sister chromatid apposition. PMID- 1505033 TI - Three-dimensional solution structure of the src homology 2 domain of c-abl. AB - SH2 regions are protein motifs capable of binding target protein sequences that contain a phosphotyrosine. The solution structure of the abl SH2 product, a protein of 109 residues and 12.1 kd, has been determined by multidimensional nuclear magnetic resonance spectroscopy. It is a compact spherical domain with a pair of three-stranded antiparallel beta sheets and a C-terminal alpha helix enclosing the hydrophobic core. Three arginines project from a short N-terminal alpha helix and one beta sheet into the putative phosphotyrosine-binding site, which lies on a face distal from the termini. Comparison with other SH2 sequences supports a common global fold and mode of phosphotyrosine binding for this family. PMID- 1505034 TI - [Multiple pregnancies in the IVF and ET programs at the Institute for Maternal and Child Care]. AB - Of the 71 clinical pregnancies achieved in the IVF and ET programme at the Institute for the Care of Mother and Child between January 1989 and June 1991 22 were multiple (30.9%). In seven cases (31.3%) spontaneous reduction occurred. A total of six patients underwent a multifoetal pregnancy reduction. PMID- 1505035 TI - [Results of transvaginal ultrasound screening for endometrial carcinoma in women at risk after menopause]. AB - Vaginal sonography was used as a prebioptic examination for screening of endometrial carcinoma in postmenopausal women in a risk group (diabetes, hypertension, obesity) without a history of haemorrhage. The examination was made in 104 women. In 23 patients the ultrasonic finding was suspect and subsequent abrasion revealed in three instances carcinoma of the endometrium (2.88%). The authors consider vaginal sonography as important prebioptic method of endometrial cancer in the risk group of women after the menopause. PMID- 1505036 TI - [Interindividual differences in the evaluation of the cardiotocogram in comparison with evaluation using computer technology]. PMID- 1505037 TI - [IUD insertion or a prescription for oral contraceptives immediately after an induced abortion]. PMID- 1505038 TI - [Fetal movement--literature review]. PMID- 1505039 TI - [New views on the etiology of premature labor]. PMID- 1505040 TI - [Why the ovary produces 3 estrogens--the biological purpose of estriol]. PMID- 1505041 TI - [Maternal mortality in the Czech Republic 1978-89]. PMID- 1505042 TI - [Perinatal and neonatal mortality in Slovakia]. PMID- 1505043 TI - [Preventive examinations in girls completing compulsory education in the Semily District in 1990]. PMID- 1505044 TI - [Results of treatment of gynecologic carcinoma based on the FIGO Annual Report, vol. 21, 1991]. PMID- 1505045 TI - [Ca 125 during normal and pathologic pregnancy]. AB - In 44 women in the first trimester of pregnancy a single examination of the Ca 125 serum level was made. In 10 women of the control group after mini interruptions of pregnancy almost in all instances serum concentrations within the normal range were recorded. In 23 women with the diagnosis of spontaneous abortion in the first trimester a mean concentration of 58 U/ml of this protein was found. In a group of 11 women with the diagnosis of imminent abortion with a favourable prognosis, on the other hand, the mean serum concentration was only 42 U/ml, which is close to the mean concentration recorded in the control group of healthy pregnant women (46 U/ml). The difference between the two groups of pathological pregnancies is, however, not statistically significant. PMID- 1505046 TI - [Side effects of amitriptyline in relation to its plasma levels]. AB - In a 21-day investigation in 15 patients with depression the authors investigated the incidence of undesirable side-effects in relation to plasma amitriptyline levels. The authors found the upper range of plasma concentrations when the patient's risk is minimal as regards serious undesirable complications. This upper limit is 350 micrograms/l; as compared with previous work, they consider amitriptyline levels from 150 to 350 350 micrograms/l safe and therapeutically effective. The authors consider investigation of plasma levels indicated in risk patients and in patients with an inadequate response to treatment. PMID- 1505047 TI - [Prevention of suicidal activity in patients with affective disorders by treatment with lithium]. AB - The authors expressed in 1984 the assumption that lithium is the drug of the phenomenon of suicidal action in affective disorders. In the present paper the authors describe in a group of 56 patients with affective disorders in the course of lithioprophylaxis a marked decline of the suicide rate at the 4% level of significance. Therefore the authors are still in favour of the view that lithium is the drug in suicidal behaviour in affective disorders. This mechanism can be explained by the antiaggressive as well as prophylactic action of lithium. In the authors' opinion it is possible that the mechanism of this action may be conditioned by the interference of lithium with the dysfunction of the central serotonergic system. PMID- 1505048 TI - [A university for the third age in Olomouc]. PMID- 1505049 TI - [Development of diagnostic classification systems in psychiatry]. AB - The author presents a historical account of classifications of mental disorders. He follows the development from simple classifications at the onset of the 19th century via Morel's, Kraepelin's, Kuffner's and Bleuler's classification to the new diagnostic classification of North American psychiatrists (DSM-III), International classification of diseases (ICD 10) to the contemporary multiaxial classification of mental disorders. PMID- 1505050 TI - [Terminology problems in schizophrenia]. AB - The author submits a new classification of schizophrenias, schizotype, hallucinatory and other disorders as found in the 10th revision of the International Classification of Diseases (ICD 10) in the chapter bearing the code F20-F29. Some new units will be found (post-schizophrenic depressions, schizotype disorders); paraphrenia and paranoia are no longer separate units. The new revision will be valid from Jan. 1, 1993; by a five-digit classification it will make as regards symptoms and course of mental disorders a more accurate diagnosis possible. PMID- 1505051 TI - [Results, problems and perspectives of modern classification systems in psychiatry]. AB - The new international classification of mental disorders (ICD 10) changes to a considerable extent the logical pattern, terminology and nomenclature of mental diseases. The prerequisite for its understanding is knowledge of general principles of medical classification and knowledge of basic theoretical problems associated with the classification of mental disorders. The paper summarizes these areas. PMID- 1505052 TI - [Use of automated quantitative analysis of electroencephalograms in the diagnosis of dementia]. AB - The submitted paper demonstrates the differential diagnostic value of automatic quantitative analysis of electroencephalograms in the diagnosis of dementia and functional mental disorders in old age. By quantitative autoregression analysis of electric activity of the brain in a group of 53 hospitalized patients (incl. 33 cases of dementia) the conclusions of visual analysis were confirmed as well as the comparability of results obtained by other methods of automatic analysis. Signs characterizing the electroencephalogram in dementia (reduced ratio of alpha activity and increase of slow activity, low value of A/T index, shift of the peak frequency towards slow activity) make differential diagnosis of dementia in organic diseases from pseudodementia possible. Analysis of the results indicates that automatic analysis can be very successful in the detection of Alzheimer's disease. PMID- 1505053 TI - [Intensive psychiatric care of patients with psychogenic eating disorders]. AB - The authors summarize their therapeutic results in anorexia nervosa achieved at the unit of specialized care for eating disorders at the Psychiatric Clinic of the First Medical Faculty, Charles University, Prague. They find that applications for hospitalization of these patients have a rising trend and that in recent years in the unit mainly patients with severe forms of these diseases are admitted. During the past 7 years in the unit a total of 147 patients were hospitalized. By comprehensive regime treatment 84% of the patients with bulimia nervosa. As to basic symptoms, in bulimia nervosa the results were achieved in vomiting and bulimic attacks and in anorexia nervosa as regards appetite, hunger and general attitude to food. Finally the authors summarize the advantages of the unit specialized care for psychogenic eating disorders. PMID- 1505054 TI - [Results of a clinical trial of levoprotiline]. AB - The authors submit results of a double blind clinical trial of levoprotiline controlled by maprotiline. In the multicentre study (which is processed and interpreted in stages) participated after written informed consent 58 patients with the diagnosis of a major depressive disorder. During the first three weeks the results of levoprotiline and maprotiline (from 26 patients each) were processed. The trial lasted 42 days. The psychopathology of the patients was evaluated by independent blind raters by means of Montgomery and Asberg's scale (MADRS), Hamilton's scale for depression (HRDS) and general clinical impression (CGI). In all patients also the pharmacological and EEG response was assessed. In comparison to maprotiline, levoprotiline was clinically ineffective. Its plasma levels (40 ng/ml) were one third to one half of the values obtained with maprotiline in the same daily dosage (150 mg). Although levoprotiline has an EEG profile typical for classical thymoleptics, its clinical antidepressive action is negligible. PMID- 1505055 TI - Induction of class 3 aldehyde dehydrogenase in the mouse hepatoma cell line Hepa 1 by various chemicals. AB - The mouse hepatoma cell line Hepa-1 was shown to express an aldehyde dehydrogenase (ALDH) isozyme which was inducible by TCDD and carcinogenic polycyclic aromatic hydrocarbons. The induced activity could be detected with benzaldehyde as substrate and NADP as cofactor (B/NADP ALDH). As compared with rat liver and hepatoma cell lines, the response was moderate (maximally 5-fold). There was an apparent correlation between this specific form of ALDH and aryl hydrocarbon hydroxylase (AHH) in the Hepa-1 wild-type cell line--in terms of inducibility by several chemicals. However, the magnitude of the response was clearly smaller for ALDH than for AHH. Southern blot analysis showed that a homologous gene (class 3 ALDH) was present in the rat and mouse genome. The gene was also expressed in Hepa-1 and there was a good correlation between the increase of class 3 ALDH-specific mRNA and B/NADP ALDH enzyme activity after exposure of the Hepa-1 cells to TCDD. It is concluded that class 3 ALDH is inducible by certain chemicals in the mouse hepatoma cell line, although the respective enzyme is not inducible in mouse liver in vivo. PMID- 1505056 TI - 32P-postlabelling analysis of DNA adducts from Fischer-344 rats administered 2,4 diaminotoluene. AB - Using 32P-postlabelling and thin layer chromatography, DNA adduct formation by the potent animal carcinogen 2,4-diaminotoluene in Fischer-344 rats was investigated. DNA from four different organs, liver, mammary gland, kidney and lung, were examined for adducts following single administration of this compound. DNA binding was detected in all four organs, with each producing one major and two minor adduct spots on autoradiograms. The adducts induced were qualitatively identical among the different organs, but quantitative differences were observed. The two target organs of 2,4-diaminotoluene induced carcinogenesis, the liver and mammary gland produced higher adduct yields, with levels up to 30-times higher than those for the two non-target organs. Since the liver is the principal target for 2,4-diaminotoluene induced carcinogenesis, we further examined DNA adducts from this site for the effects of different doses and time points. DNA binding in liver was detected following doses as low as 4.1 mumol/kg. At the highest concentration examined (2046 mumol/kg), the level of the major adduct was 29.2 adducted nucleotides per 10(7) total nucleotides. The yields for the two minor adducts were approximately one-tenth that for the major adduct. Following a 410 mumol/kg dose, DNA adduct removal over time was examined. DNA adduct removal exhibited biphasic kinetics, with a rapid initial phase followed by a slower rate of elimination. Up to 60% of maximum adduct levels persisted after 2 weeks. DNA binding by 2,4-diaminotoluene was also compared to that by its weakly carcinogenic analog, 2,4-dinitrotoluene. The two compounds produced identical adduct patterns, suggesting that they share common metabolites and adducts. Adduct yields from 2,4-dinitrotoluene, however, were lower. The results of our studies suggest that the differences in carcinogenic potency between 2,4 diaminotoluene and 2,4-dinitrotoluene, as well as the organotropic effects of 2,4 diaminotoluene may be explained, in part, by quantitative differences in the extent of DNA adduct formation. PMID- 1505057 TI - A mechanism for the development of Clara cell lesions in the mouse lung after exposure to trichloroethylene. AB - Female CD-1 mice exposed to trichloroethylene (6 h/day) at concentrations from 20 2000 ppm developed a highly specific lung lesion after a single exposure, characterised by vacuolation of the Clara cells, the number of cells affected increasing with increasing dose level. At the highest dose levels pyknosis of the Clara cells was apparent. After 5 days of repeated exposures the lesion had resolved but exposure of mice following a 2-day break resulted in recurrence of the lesion. The changes in mouse lung Clara cells were accompanied by a marked loss of cytochrome P-450 activities. No morphological changes were seen in the lungs of rats exposed to either 500 or 1000 ppm trichloroethylene. Isolated mouse lung Clara cells were shown to metabolize trichloroethylene to chloral, trichloroethanol and trichloroacetic acid. Chloral was the major metabolite. Trichloroethanol glucuronide was not detected. In comparative experiments using mouse hepatocytes the major metabolites were trichloroethanol and its glucuronide conjugate. The activity of UDP-glucuronosyltransferase was compared in mouse lung Clara cells and hepatocytes using two phenolic substrates and trichloroethanol. Hepatocytes readily formed glucuronides from all three substrates whereas Clara cells were only active with the two phenolic substrates. The three major metabolites of trichloroethylene, chloral, trichloroethanol and trichloroacetic acid were each dosed to mice and of these metabolites, only chloral had an effect on mouse lung causing a lesion (Clara cell) identical to that seen with trichloroethylene. It is proposed that the failure of Clara cells to conjugate trichloroethanol leads to an accumulation of chloral which results in cytotoxicity. The known genotoxicity of chloral suggests that this lesion may be related to the development of lung tumours in mice exposed to trichloroethylene by inhalation. PMID- 1505058 TI - The anti-carcinogenic plant compound indole-3-carbinol differentially modulates P450-mediated steroid hydroxylase activities in mice. AB - Indole-3-carbinol (I3C), a component of cruciferous vegetables, exhibits anti carcinogenic activity in a variety of model systems. This activity has been attributed in part to the induction of cytochrome P450 CYP1A subfamily members and the resulting increased metabolic inactivation of chemical carcinogens. The present study was undertaken to assess the effects of I3C on several constitutive P450 activities that contribute to both carcinogen and steroid hormone metabolism. Mice were administered I3C in their diet at estimated daily doses of 250, 500 and 750 mg/kg for 1 week. Liver microsomes from treated and untreated mice were subsequently assayed for CYP1A-mediated ethoxy-resorufin O-deethylase (EROD) activity, estradiol 2-hydroxylase activity and seven different testosterone hydroxylase activities. I3C elevated EROD, estradiol 2-hydroxylase and testosterone 6 alpha-hydroxylase activities in a dose-dependent manner. The other six testosterone hydroxylase activities were not significantly affected by in vivo treatment with I3C. In addition to its effects on steroid hydroxylase activities, I3C also elevated NADPH-cytochrome P450 reductase activity, a necessary component to the P450 monooxygenase system. We next examined the direct in vitro effects of I3C and its acid condensation products, as are generated in the stomach following ingestion, on the P450 catalytic activities. Testosterone 6 beta-hydroxylase, the major testosterone hydroxylase activity in untreated mice, was significantly inhibited (IC50 approximately 12 micrograms/ml) by the acid condensation products of I3C. In contrast, all other P450 activities were not appreciably affected by I3C or its acid condensation products. These results indicate that I3C can elicit both inductive and suppressive effects on the constitutive P450s that participate in carcinogen and steroid hormone metabolism. This pleiotropic effect on hepatic catalytic enzymes may contribute to the anti carcinogenic properties of this compound. PMID- 1505059 TI - Activity of the human metallothionein promoter (hMT-IIA) in cell populations isolated from varying depths in multicell spheroids following exposure to cadmium. AB - In order to evaluate whether tumor microenvironment might influence the response of the metallothionein promoter to heavy-metal exposure, we transfected HT-29 colon carcinoma cells with the vector phMTIIA-CAT-neo, containing a fusion gene consisting of 426 bp of the human metallothionein-IIa (hMT-IIA) promoter immediately upstream of the bacterial chloramphenicol acetyl transferase (CAT) gene. We grew one of the stable transfectants (clone 20) as three-dimensional multicell tumor spheroids, exposed them to CdCl2 and measured CAT expression in cells isolated from various depths into the spheroids. Cellular populations were isolated by flow cytometry on the basis of Hoescht 33342 fluorescence intensity, taking advantage of the dye's diffusion gradient to isolate cells from inner (dim) and outer (bright) regions of stained spheroids. When intact spheroids were incubated for 18 h in the presence of 5 microM CdCl2, CAT activity was induced in all cell fractions isolated from the spheroids, but induction was 10-fold greater in cells in the outermost fraction (fraction 10) than inner fraction (fraction 2). When spheroids were dissociated, sorted into individual fractions and then incubated with cadmium, CAT expression was maximized in all fractions. Exposure of intact spheroids to 30 microM CdCl2 resulted in increased CAT induction in cells isolated from the internal fractions of the spheroids. The data suggest that limited diffusion of cadmium through cells organized in a tissue-like arrangement may account for the lower levels of hMT-IIA promoter activity observed in cells collected from increasing depths into the spheroids. PMID- 1505060 TI - Glutathione depletion, lipid peroxidation, DNA double-strand breaks and the cytotoxicity of 2-bromo-3-(N-acetylcystein-S-yl)hydroquinone in rat renal cortical cells. AB - The mechanisms involved in the cytotoxicity of 2-bromo-3-(N-acetylcystein-S yl)hydroquinone, a model compound for hydroquinone derived mercapturic acids, were investigated in rat renal proximal tubule cells. 2-Bromo-3-(N-acetylcystein S-yl)hydroquinone induced a time- and concentration-dependent decrease in cell viability and in the levels of cellular glutathione. Antioxidants such as N,N' diphenyl-p-phenylene diamine and ascorbic acid and the iron chelator desferrioxamine very efficiently protected the cells from 2-bromo-3-(N acetylcystein-S-yl)hydroquinone without influencing glutathione depletion. The acetoxymethyl ester of the Ca2+ chelator Quin-2, the inhibitor of the Ca(2+)- and Mg(2+)-dependent endonucleases, aurintricarboxylic acid and the poly(ADP-ribose) polymerase inhibitor 3-aminobenzamide also ameliorated 2-bromo-3-(N-acetylcystein S-yl)hydroquinone cytotoxicity. Moreover, 2-bromo-3-(N-acetylcystein-S yl)hydroquinone depleted Ca2+ from isolated kidney mitochondria, increased the amount of malondialdehyde in rat kidney cells and induced DNA double-strand breaks in renal cells in culture. These results suggest that renal cells oxidize 2-bromo-3-(N-acetylcystein-S-yl)hydroquinone to the corresponding quinone; this soft electrophile reacts rapidly with glutathione, thus depleting cellular glutathione concentrations as indicated by the tentative identification of a 2 bromo-3-(N-acetylcystein-S-yl)hydroquinone thioether in the incubation medium of renal cells treated with the mercapturate. As a result of the massive glutathione depletion, peroxidative mechanisms then cause an elevation of the cytosolic concentrations of ionized calcium; impairment of the ability of the mitochondria to sequester Ca2+ plays an important role in the elevation of the Ca2+ concentration. Finally, activation of Ca(2+)- and Mg(2+)-dependent endonucleases results in DNA damage and cell death. PMID- 1505061 TI - Monolayer characteristics and thermal behaviour of phosphatidic acids. AB - The monolayer and thermal behaviour of different phosphatidic acids are presented. At neutral pH and 22 degrees C dilauroylphosphatidic acid and unsaturated phosphatidic acids form liquid-expanded monolayers, while dipalmitoyl and distearoylphosphatidic acid form condensed monolayers. Dimyristoylphosphatidic acid undergoes a transition from the liquid-expanded to the condensed state. With long-chain saturated and unsaturated phosphatidic acids little change in molecular area is observed between pH 2 and 7. In contrast, the short chain saturated phosphatidic acids, dilauroyl- and dimyristoylphosphatidic acids, undergo a condensation in the pH range 2 to 7. This is so in spite of the fact that the phosphoric acid group dissociates and the phosphatidic acid molecule attains one negative charge over this pH range. This finding is interpreted to indicate that the electrostatic repulsion between negatively charged phosphatidic acid molecules is compensated for or even outweighed by other intermolecular forces. Hydrogen bonding at the lipid/water interface is supposed to play a major role. All phosphatidates studied exhibit a significant expansion in the pH range 7 to 12. The second apparent pK of the primary phosphate group of phosphatidic acids is 8.6 and the expansion observed in this pH range is therefore due to electrostatic repulsion. At neutral pH the ether analogues of saturated phosphatidic acids have monolayer properties similar to those of the ester compounds. Considering the total pH range of 2 to 12 studied the force-area curves of the ether analogues are more condensed compared to the ester compounds. Synthetic phosphatidates and their ether analogues give reversible sharp crystal(gel)-to-liquid crystal transitions while the naturally occurring egg phosphatidate gives a broad, asymmetric one. The transition temperature Tm of saturated phosphatidates increases with increasing hydrocarbon chain length and at a given chain length Tm decreases markedly with unsaturation. The Tm values of the ether analogues are about 10 degrees C higher and the delta H values are 10-15% lower than those of the corresponding esters. PMID- 1505062 TI - Anthrylvinyl-labeled phospholipids as fluorescent membrane probes. The action of melittin on multilipid systems. AB - The interaction of melittin with multicomponent lipid mixtures composed of phosphatidylcholine, sphingomyelin and phosphatidylserine or phosphatidylglycerol was investigated by measuring the intrinsic fluorescence of the peptide, steady state fluorescence anisotropy of, and Trp-fluorescence energy transfer to fluorescent analogs of the same phospholipids bearing the anthrylvinyl fluorophore in one of the aliphatic chains at various distances from the polar head group. Based on the finding that at high lipid/peptide ratio the peptide induces unequal changes in the fluorescence parameters of phospholipid probes differing structurally only in their polar head groups, it is concluded that melittin induces lipid demixing in its nearest environment. Comparison of the fluorescence energy transfer from Trp to different lipid probes indicates that the depth of penetration of melittin into the bilayer depends on the polar head group composition of the phospholipid matrix and that certain segments of the melittin chain display a specific affinity for a given lipid head group. PMID- 1505064 TI - Synthesis of enantiomerically pure lysophosphatidylinositols and alkylphosphoinositols. AB - A convenient synthesis for enantiomeric pure 1-O-(1'-O-alkyl-sn-glycero-3' phospho)-D (or L)-myo-inositol, 1-O-(1'-O-acyl-sn-glycero-3'-phospho)-D (or L) myo-inositol and alkylphospho-1-D (or L)-myo-inositol has been described. Starting from myo-inositol, penta-O-acetyl-myo-inositol was made in five steps. Then enantiomeric purification was done by a diastereomeric salts separation method, and the purity of each enantiomer was spectroscopically measured (19F NMR). The phosphodiester was made via phosphoramidites. The enantiomeric products (greater than 99% optical purity) of all compounds were easily obtained in large quantities (5-10 g). Synthetic phosphatidylinositol analogues of precisely defined structure and configuration are interesting tools for studying signal transduction mechanism and cell activity modulation. PMID- 1505063 TI - Rat cerebellar granule cells in culture associate and metabolize differently exogenous GM1 ganglioside molecular species containing a C18 or C20 long chain base. AB - A study has been made of the association properties of the two GM1 ganglioside molecular species GM1-C18 and GM1-C20 (containing C18 and C20 long chain bases, respectively) to rat cerebellar granule cells in culture. Both gangliosides recognized, to the same extent, and associated with them to give a form of association, the trypsin-labile form. This form was removed by treatment with trypsin enzyme. Both gangliosides associated stably with the cells to become components of the cell membranes. Although similar amounts of the two gangliosides entered the cells, being then metabolized, the time course of the association was different for the two gangliosides: after 15 h of ganglioside cell incubation the amount of GM1-C18 inserted into the cell membrane was 2.43 times higher than that of GM1-C20. PMID- 1505065 TI - Some oxidation products of ethoxyquin including those found in autoxidising systems. AB - 2,4-Dimethyl-6-ethoxyquinoline (2), 1,2-dihydro-6-ethoxy-2,2,4-trimethylquinoline nitroxide (3), 2,6-dihydro-2,2,4-trimethyl-6-quinone imine N-oxide (4), 2,6 dihydro-2,2,4-trimethyl-6-quinone imine (5), 1.8' -di(1,2-dihydro-6-ethoxy-2,2,4 trimethylquinoline) (6) and 1,2-dihydro-6-hydroxy-2,2,4-trimethylquinoline (7) have been prepared from 1,2-dihydro-6-ethoxy-2,2,4-trimethylquinoline (1) (ethoxyquin) and their spectroscopic properties (UV, IR, mass and NMR) examined. PMID- 1505066 TI - Identification of (all-cis)-6,9,12,15-octadecatetraenoic acid in Ribes nigrum and fish oils: chemical and physical characterization. AB - In this report, we show that the non-conjugated octadecatetraenoic acid found in the oil of the seeds from Ribes nigrum is identical to the C18-polyunsaturated fatty acid previously isolated in a number of fish oils and seed oils. Evidence obtained from mass spectral data of its triazolopyridine derivative clearly indicates the presence of methylene-interrupted double bonds. Comparison with authentic material prepared by chemical synthesis provides further confirmation of the (all-cis)-6,9,12,15-octadecatetraenoic acid structure. The (all-cis) 4,8,12,15-structural arrangement erroneously attributed to this acid in several literature reports is thus definitely ruled out. PMID- 1505067 TI - Enterocolitis due to methicillin-resistant Staphylococcus aureus--report of two cases. AB - Two cases of postoperative enterocolitis due to methicillin-resistant Staphylococcus aureus (MRSA) after gastrectomy were experienced. Case 1: A 59 year-old male underwent subtotal gastrectomy for advanced gastric cancer. Diffuse peritonitis progressed after the first operation, so reoperation for drainage was required. Two days after the second operation, a profuse watery diarrhea developed. Case 2: A 46-year-old male underwent total gastrectomy for early gastric cancer. On the fourth postoperative day, frequent vomiting and cholera like diarrhea started, followed by profound shock several hours later. Both cases were treated successfully by the administration of vancomycin. Stool cultures of both cases revealed MRSA and it had the same minimal inhibitory concentration, coagulase type and enterotoxin type, so that nosocomial infection was indicated. PMID- 1505068 TI - Clinical assessment of the knowledge base of an expert system for data analysis in laboratory medicine. AB - Despite the apparent demand for a consultation system, only a few expert systems have been developed for laboratory medicine. Some studies on the diagnostic precision of such systems have been reported, but the efficiency of their knowledge bases has not yet been investigated. An expert system, named BLOOD, for data analysis in a hematology laboratory, which is written in C-Prolog and runs on VAX-station, has already been reported to have excellent diagnostic reliability and ability to cope with the fuzziness involved in clinical diagnostic procedures. A quantitative examination of the knowledge base of BLOOD using real laboratory data from 58 patients diagnosed as having iron deficiency anemia clearly revealed the verbosity of the knowledge base, and proved that it was effective for obtaining a group of essential diagnostic rules. PMID- 1505069 TI - Cytogenetic studies of human malignant melanoma cell lines. AB - Cytogenetic studies were performed on six cell lines derived from three patients suffering from malignant melanomas. The modal chromosome numbers were in the hypotriploid to hypertetraploid ranges and both the numerical and structural aberrations of chromosomes were found. Aberrations were most frequently observed in chromosomes 1, 6 and 7. Deletion of 1q was consistently present in all cell lines, while loss of 6q was observed in two cell lines of case 1. Translocations t (Y; 6) and t (6;?) occurred in one cell line from case 3. An increased number of copies of chromosome 7 was a characteristic feature of the cell lines from case 2. Since positive correlation between the expression of EGF receptors and an increased dosage of chromosome 7 has been reported for malignant melanomas and the gene for EGFR has been mapped to band 7p12-p13, this phenomenon might be of importance for the proliferation of malignant melanoma. The findings of the present study are generally in agreement with the data previously published in the literature, indicating the existence of specific non-random chromosome lesions during melanoma development. PMID- 1505070 TI - Therapeutic efficacy of combination of antitumor agent with AHC-52 against multidrug-resistant cells in the intravenously inoculated P388 leukemia model. AB - To predict the clinical effect on leukemic disease of a combination regimen developed to circumvent multidrug resistance (MDR), we tested various antitumor agents in the presence and absence of AHC-52, a sensitizing agent for multidrug resistant cells, in the i.v.-i.v. model of murine leukemia. In this model system, sensitive and resistant P388 murine leukemia cells are inoculated i.v. into mice, and each antitumor agent is injected via the i.v. route. Vincristine (VCR) had no effect on the survival of mice bearing VCR-resistant P388, a relatively poorly resistant subline, when given either as a single agent or in combination with AHC 52. In contrast, adriamycin (ADR) alone had no effect on these mice, but its combination with AHC-52 resulted in significant survival, the maximal value achieved being 196% (treated mice/control animals, T/C). Etoposide (VP-16) strongly enhanced survival, even when used alone, and this effect was markedly potentiated by AHC-52. Combination of any antitumor drug with AHC-52 was ineffective in mice bearing ADR-resistant P388, a highly resistant subline. On the other hand, AHC-52 strongly augmented the therapeutic efficacy of these antitumor agents in mice bearing the sensitive parent P388 leukemia, producing some curative effects. On the basis of these results, the feasibility of this type of combination therapy is discussed. PMID- 1505071 TI - Nitrogen mustard-DNA interaction in melphalan-resistant mammary carcinoma cells with elevated intracellular glutathione and glutathione-S-transferase activity. AB - We examined the relationship between intracellular levels of glutathione (GSH), glutathione-S-transferase (GST) activity, and the kinetics of DNA cross-links induced by the bifunctional alkylating drugs melphalan (MLN), chlorambucil (CLB), and mechlorethamine (HN2) in a rat mammary carcinoma cell line (WT) and in a subline selected in vitro for primary resistance to MLN (MLNr, 16-fold resistance). MLNr cells exhibit a 2-fold increase in intracellular GSH concentration and an approximately 5-fold increase in GST activity as compared with the parent cells. They are cross-resistant to a variety of drugs, including CLB (6-fold) and HN2 (14-fold). Treatment of WT cells with 30 microM MLN or CLB induced a significant accumulation of DNA-DNA cross-links for up to 8 h, which decreased over a 24-h period. In MLNr cells, no significant cross-link formation was induced by either MLN of CLB at any time between 0 and 24 h. Doses of up to 100 microM MLN failed to induce cross-links in MLNr cells. Formation of cross links was observed immediately after treatment with HN2 in both cell lines and was followed by a subsequent decrease during a 24-h incubation in drug-free medium. At an equimolar concentration (30 microM), the numbers of HN2-induced cross-links were significantly lower in MLNr cells than in WT cells. However, treatment of MLNr cells with 60 microM HN2 resulted in cross-link levels similar to those obtained using 30 microM HN2 in WT cells. The 35% decrease in MLN accumulation observed in MLNr cells could not entirely explain the absence of cross-links, since thin-layer chromatographic analysis demonstrated that both cell lines accumulate a significant amount of MLN and metabolize it to the same extent. Significant amounts of MLN were also detected in nuclei isolated from WT and MLNr cells that had been treated with 30 microM [14C]-MLN. Intracellular depletion of GSH by a nontoxic concentration of L-buthionine-(S, R)-sulfoximine (BSO, 100 microM; about 70% GSH depletion) significantly sensitized MLNr cells to MLN and increased cross-link formation. A nontoxic concentration (50 microM) of ethacrynic acid (EA, an inhibitor of GST showing some specificity for Yc/Yp subunits) also sensitized MLNr cells to MLN and increased cross-link formation. Our data demonstrate that both EA and BSO are effective modulators of nitrogen mustard cytotoxicity in tumor cells resistant to alkylating drugs.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1505072 TI - Adozelesin, a potent new alkylating agent: cell-killing kinetics and cell-cycle effects. AB - Adozelesin (U-73975) was highly cytotoxic to V79 cells in culture and was more cytotoxic than several clinically active antitumor drugs as determined in a human tumor-cloning assay. Phase-specificity studies showed that cells in the M+early G1 phase were most resistant to adozelesin and those in the late G1 + early S phase were most sensitive. Adozelesin transiently slowed cell progression through the S phase and then blocked cells in G2. Some cells escaped the G2 block and either divided or commenced a second round of DNA synthesis (without undergoing cytokinesis) to become tetraploid. Adozelesin inhibited DNA synthesis more than it did RNA or protein synthesis. However, the dose needed for inhibition of DNA synthesis was 10-fold that required for inhibition of L1210 cell growth. The observation that cell growth was inhibited at doses that did not cause significant inhibition of DNA synthesis and that cells were ultimately capable of completing two rounds of DNA synthesis in the presence of the drug suggests that adozelesin did not exert its cytotoxicity by significant inhibition of DNA synthesis. It is likely that adozelesin alkylates DNA at specific sites, which leads to transient inhibition of DNA synthesis and subsequent G2 blockade followed by a succession of events (polyploidy and unbalanced growth) that result in cell death. PMID- 1505073 TI - Mechanism-based model for tumor drug resistance. AB - The development of tumor resistance to cytotoxic agents has important implications in the treatment of cancer. If supported by experimental data, mathematical models of resistance can provide useful information on the underlying mechanisms and aid in the design of therapeutic regimens. We report on the development of a model of tumor-growth kinetics based on the assumption that the rates of cell growth in a tumor are normally distributed. We further assumed that the growth rate of each cell is proportional to its rate of total pyrimidine synthesis (de novo plus salvage). Using an ovarian carcinoma cell line (2008) and resistant variants selected for chronic exposure to a pyrimidine antimetabolite, N-phosphonacetyl-L-aspartate (PALA), we derived a simple and specific analytical form describing the growth curves generated in 72 h growth assays. The model assumes that the rate of de novo pyrimidine synthesis, denoted alpha, is shifted down by an amount proportional to the log10 PALA concentration and that cells whose rate of pyrimidine synthesis falls below a critical level, denoted alpha 0, can no longer grow. This is described by the equation: Probability (growth) = probability (alpha 0 less than alpha-constant x log10 [PALA]). This model predicts that when growth curves are plotted on probit paper, they will produce straight lines. This prediction is in agreement with the data we obtained for the 2008 cells. Another prediction of this model is that the same probit plots for the resistant variants should shift to the right in a parallel fashion. Probit plots of the dose-response data obtained for each resistant 2008 line following chronic exposure to PALA again confirmed this prediction. Correlation of the rightward shift of dose responses to uridine transport (r = 0.99) also suggests that salvage metabolism plays a key role in tumor-cell resistance to PALA. Furthermore, the slope of the regression lines enables the detection of synergy such as that observed between dipyridamole and PALA. Although the rate-normal model was used to study the rate of salvage metabolism in PALA resistance in the present study, it may be widely applicable to modeling of other resistance mechanisms such as gene amplification of target enzymes. PMID- 1505074 TI - Potentiation of the antitumor activity of 5-trifluoromethyl-2'-deoxyuridine by the use of depot forms of the parent compound. AB - 5-Trifluoromethyl-2'-deoxyuridine (CF3dUrd), an antitumor agent, is known to be short-lived in human plasma. Since its rapid elimination from the bloodstream seems to have descouraged the clinical evaluation of this drug, we explored the potential use of masked derivatives of CF3dUrd as "depot" forms of the parent compound. First, we observed that the toxicity of CF3dUrd against HeLA cells in culture was 10(4) times greater for a 24-h treatment as compared with a 1-h treatment at identical concentrations of the drug, which suggests the importance of using a prolonged treatment period. In fact, the divided dosing of CF3dUrd to L1210-bearing mice was markedly more effective than its single administration. 5' O-Hexanoyl-, N3-p-butylbenzoyl-, 5'-O-benzyloxy-methyl-, and 3'-O-benzyl-CF3dUrd were found to be effective in maintaining the CF3dUrd concentration in plasma. The oral doses of these agents required to achieve 50% growth inhibition (ED50) in mice bearing sarcoma 180 tumors were 19, 34, 10, and 13 mg kg-1 day-1, respectively, whereas that of CF3dUrd was 63 mg kg-1 day-1. The ED50 values for these compounds were inversely correlated with the residence time of CF3dUrd in plasma. The therapeutic indices of these compounds, calculated as the dose producing a 50% inhibition of body-weight gain (IB50) divided by the ED50 value (1.89, 1.21, 1.40, and 2.15, respectively), were significantly higher than that of CF3dUrd (0.78). Consequently, these depot forms of CF3dUrd, particularly 3'-O benzyl-CF3dUrd, are expected to be more useful than the parent compound as antitumor agents. PMID- 1505075 TI - Pharmacokinetics of liposome-entrapped cis-bis-neodecanoato-trans-R,R-1,2 diaminocyclohexane platinum(II) and cisplatin given i.v. and i.p. in the rat. AB - The pharmacokinetics of liposome-entrapped cis-bis-neodecanoato-trans-R,R-1,2 diaminocyclohexane platinum(II) (L-NDDP) and cisplatin (CDDP) were studied after i.v. and i.p. administration of an equimolar dose (11 and 5 mg/kg for L-NDDP and CDDP, respectively) in the rat. The systemic absorption following i.p. administration was faster in rats receiving CDDP than in those receiving L-NDDP. Peak serum platinum (Pt) levels were observed at 30 min and 12 h after the i.p. administration of CDDP and L-NDDP, respectively. Administration by the i.v. route did not significantly alter the serum Pt levels for either compound. However, serum Pt levels were 2-3 times greater in animals treated with L-NDDP than in those treated with CDDP. The estimated pharmacokinetic parameters for each drug were independent of the route of administration, except for the clearance (Cl) of CDDP, which increased 2-fold following i.p. administration. In addition, significant differences in pharmacokinetic parameters were observed between drug treatment groups that were independent of the route of administration: the serum Pt area under the concentration-time curve (AUC) was higher and the volume of distribution at steady state (Vdss) was lower in rats receiving L-NDDP. Pt levels measured at 6 h in the peritoneal fluid, peritoneal tissue, and intestine of rats receiving i.p. L-NDDP were higher than those observed in rats receiving either i.v. L-NDDP or CDDP by either route. Pt levels measured in the liver and spleen of rats receiving L-NDDP were independent of the route of administration and were significantly higher than those determined in rats treated with CDDP. In contrast, kidney Pt levels were lower in rats receiving L-NDDP than in rats receiving CDDP by either route. These results suggest that the prolongation of the mean retention time of L-NDDP in the peritoneum achieved after i.p. administration without compromising the systemic distribution of the drug may result in a significant enhancement of the therapeutic efficacy of L-NDDP against malignancies confined to the peritoneal cavity as compared with that of i.p. CDDP. PMID- 1505076 TI - Minocycline in combination with chemotherapy or radiation therapy in vitro and in vivo. AB - In the present study the potential of minocycline, a semisynthetic tetracycline that inhibits collagenase activity in vivo, as an adjuvant to standard anticancer therapies was explored in vitro and in vivo. In EMT-6 cells, minocycline proved to be only minimally cytotoxic, producing a 50% cell kill at concentrations of 132 and 220 microM in normally oxygenated and hypoxic cells, respectively, after 24 h exposure to the drug. In vitro, there appeared to be no interaction between minocycline and cisplatin (CDDP), melphalan, 4-hydroperoxycyclophosphamide, or radiation. In tumor-cell survival studies using the FSaIIC murine fibrosarcoma, short-term treatment with minocycline (5 x 5 mg/kg given over 24 h) was only minimally cytotoxic and did not alter the tumor response to a range of radiation doses. However, when minocycline (5 x 5 mg/kg given over 24 h) was added to treatment with cyclophosphamide, there was a 4-fold increase in FSaIIC tumor-cell killing across the dose range of cyclophosphamide doses tested, whereas the killing of bone marrow granulocyte macrophage colony-forming units (CFU-GM) remained unchanged. The Lewis lung carcinoma was used to assess the response of both the primary tumor and metastatic lung disease to treatment with minocycline (14 x 5 mg/kg) given alone or in combination with several cytotoxic anticancer drugs or with radiation delivered locally to the primary tumor. Of the various therapies tested, minocycline proved to be especially effective as an addition to treatment with cyclophosphamide both in increasing the response of the primary tumor and in reducing the number of lung metastases. The tumor growth delay produced by melphalan, radiation, Adriamycin, and bleomycin was also increased by the addition of minocycline to these therapies. These results indicate that minocycline given in clinically achievable doses may be an effective addition to some standard therapeutic regimens and that the mechanism of modulation by minocycline is likely to involve an effect of the drug on the host and not its direct interaction with other therapeutic modalities at the level of the tumor cell. PMID- 1505077 TI - Assessment of antineoplastic agents by MTT assay: partial underestimation of antiproliferative properties. AB - In the present study a slightly modified MTT assay was used in conjunction with cell counting to determine the antiproliferative efficacy of N-(2-chloroethyl)-N nitroso-N'-2-hydroxyethylurea (HECNU), vinblastine, and hexadecylphosphocholine (HPC) in a panel of six tumor cell lines. This panel consisted of two human (MDA MB231, MCF-7) and two rodents (1/C2, 1/C32) mammary-carcinoma cell lines as well as of two tumor cell lines of gastrointestinal origin (HT-29, KB). It was shown that the use of acid isopropanol as a solvent of the formazan crystals produced correlations between cell number and absorption that were as good as, if not better than, those seen after dimethylsulfoxide (DMSO) application. The optimal period of incubation with the MTT dye was 2 h. A comparison of the antiproliferative activity of HECNU revealed that the HT-29 cell line was most resistant [50% inhibition concentration (IC50), 138.7 mumol/l], followed by MCF-7 cells (IC50, 127.7 mumol/l), whereas MDA-MB231 cells showed the highest sensitivity (IC50, 6 mumol/l). Vinblastine induced the highest (MCF-7 cells; IC50, 0.68 nmol/l) and the lowest (1/C2 cells; IC50, 7.69 nmol/l) degrees of growth inhibition in cell lines derived from mammary carcinoma. This contrasted with the activity of HPC, which was considerably less effective in the four mammary-carcinoma cell lines (IC50 from 29.4 to 69.9 mumol/l) than in the two cell lines of gastrointestinal origin (IC50, 1.9 and 3.1 mumol/l). Interestingly, treatment with HPC stimulated the growth of 1/C32 cells in the lower dose range. After treatment with HECNU, the average IC50 value determined in the MTT assay was 2.4-fold that disclosed by cell counting, whereas the average values found for HPC and vinblastine by both methods corresponded fairly well, with the respective values obtained using the MTT assay being only 26% and 14% higher than those measured by cell counting. A dose-dependent increase in the mean size of MCF-7 cells was observed after exposure to HECNU, which--if taken into account- considerably reduced underestimation of this parameter by the MTT assay. No variation in cell size was noted following treatment with HPC and vinblastine. Thus, depending on the antitumor agent used, the MTT assay can result in slight or even considerable underestimation of the antitumor efficacy of certain compounds and may need correction by consideration of the effect of the drugs on cell size. PMID- 1505079 TI - In vitro screening of crude extracts and pure metabolites obtained from marine invertebrates for the treatment of breast cancer. AB - A total of 15 samples (crude extracts and pure secondary metabolites) obtained from marine invertebrates collected from the offshore waters of British Columbia, Papua New Guinea, and Sri Lanka have previously been shown to exert cytotoxic activity in the in vitro L1210 leukemic bioassay. We screened these metabolites for in vitro cytotoxic activity against the drug-sensitive breast-tumor cell lines MCF-7, T-47D, ZR-75-1, and MDA-MB-231; the multidrug-resistant and P glycoprotein (Pgp)-positive breast-tumor cell lines MCF-7 Adr and MDA-A1r; and normal and malignant human breast epithelial cells (HBEC) in primary culture. Eight samples exhibited significant [drug concentration resulting in a 50% decrease in cell growth as compared with controls (ED50), less than 25 micrograms/ml] dose-dependent cytotoxicity against the drug-sensitive cell lines; the ED50 values were as low as 0.004 micrograms/ml. Five of the eight samples exhibited significant cytotoxicity against the multidrug-resistant cell lines; the ED50 values were as low as 0.0006 micrograms/ml. Incubation of MCF-7 Adr cells with varying concentrations of compounds in the presence of Adriamycin demonstrated that none of the compounds tested interfered with Pgp function. Results obtained using HBEC in primary culture showed a wide range of chemosensitivities for a given drug against tissue taken from different patients, demonstrating the uniqueness of the response of different individuals to chemotherapy. PMID- 1505078 TI - Thymidylate synthase as a target enzyme for the melanoma-specific toxicity of 4-S cysteaminylphenol and N-acetyl-4-S-cysteaminylphenol. AB - The rationale for melanoma-specific antitumor agents containing phenolic amines is based in part on the ability of the enzyme tyrosinase to oxidize these prodrugs to toxic intermediates. The phenolic amine compounds 4-S cysteaminylphenol (4-S-CAP) and N-acetyl-4-S-cysteaminylphenol (N-Ac-4-S-CAP) inhibited in situ thymidylate synthase activity in pigmented melanoma cell lines but had little or no effect on nonpigmented and nonmelanoma cell lines. Theophylline, a cyclic adenosine monophosphate (cAMP) phosphodiesterase inhibitor, increased tyrosinase activity and potentiated the inhibition of in situ thymidylate synthase by N-Ac-4-S-CAP. The inhibition of in situ thymidylate synthase by both drugs in pigmented melanoma cells correlated with the inhibition of DNA synthesis and cell growth and was not due to an indirect effect caused by inhibition of the enzyme dihydrofolate reductase. 4-S-CAP inhibition of thymidylate synthase activity in cell free extracts required oxidation of the drug. In the presence of tyrosinase, the concentration causing a 50% inhibition of thymidylate synthase activity (IC50) in cell-free extracts was less than 10 microM, but no inhibition was observed in its absence, even at a drug concentration of 500 microM. Two reducing agents, dithioerythritol and glutathione, effectively blocked the inhibition of thymidylate synthase by oxidized 4-S-CAP. In pigmented melanoma cells containing the enzyme tyrosinase, the quinone-mediated mechanism of inhibition of DNA synthesis via inhibition of thymidylate synthase may be uniquely important in the expression of phenolic amine cytotoxicity. PMID- 1505081 TI - The role of out-patient nasal endoscopy in the evaluation of chronic sinus disease. PMID- 1505080 TI - Changes in serum lipids and lipoproteins in cancer patients during chemotherapy. AB - We studied serum lipid and lipoprotein changes occurring during chemotherapy in 57 patients with chemosensitive cancers, including 18 malignant lymphomas, 18 breast carcinomas, 14 small-cell lung carcinomas, and 7 urothelial-cell carcinomas. Patients who responded favorably to chemotherapy demonstrated a significant increase in serum total cholesterol and LDL cholesterol values, with the singular exception of breast-cancer patients, who exhibited a nonsignificant decrease in both of these parameters. Serum levels of free cholesterol and HDL cholesterol did not show any significant changes. Finally, serum triglycerides tended to increase after effective chemotherapy, but this was of statistical significance only in breast-cancer patients. Although our findings were based on a rather small number of patients, they indicate that the lipid and lipoprotein disorders reported in cancer patients are reversible by effective treatment of the tumor, suggesting that these disorders are a secondary phenomenon of malignancy. PMID- 1505082 TI - Occurrence of Streptococcus pneumoniae and Haemophilus influenzae in otitis media with effusion. AB - Eighty mucoid effusion samples obtained from 56 patients with otitis media with effusion (OME) were subjected to quantitative and qualitative bacteriological analysis using standard culturing methods, direct microscopy and immunofluorescent assay. 30% of the samples contained culture-positive pathogens (H. influenzae, S. pneumoniae, B. catarrhalis), with counts never exceeding 5 x 10(5) per ml. In addition, 19% of the samples had dormant H. influenzae and S. pneumoniae, which did not grow on standard agar plates. Viable and dormant bacteria, as well as bacterial remnants, play a crucial role in the pathogenesis of OME and similarities between OME and reactive arthritis, i.e. Lyme arthritis, Reiter's syndrome and rheumatic fever, are evident. PMID- 1505083 TI - The effect of anaesthesia on tympanograms of children undergoing grommet insertion. AB - A prospective study was designed to assess the effect of anaesthesia, including nitrous oxide, on tympanometric results of children undergoing myringotomy and possible grommet insertion. 155 patients (310 ears) were examined with a pneumatic otoscope and had tympanograms performed within 1 hour of operation. The patients were then anaesthetized by a combination of intravenous and gaseous anaesthetic. Immediately before myringotomy, a tympanogram was repeated. In 13% of patients predicted to have fluid at admission, there was a change in their tympanogram after induction of anaesthesia, suggesting clearance of fluid. At myringotomy, these ears were dry. We surmise that there was displacement of fluid from the middle ear by nitrous oxide during the early stages of anaesthesia. Thus we feel that, if an otologist confidently expects to find an effusion at myringotomy, the presence of a dry tap should not change his management plan. PMID- 1505084 TI - Alterations in tympanic membrane appearance and middle ear function in 11-year old children with complete unilateral cleft lip and palate compared with healthy age-matched subjects. AB - Forty-four 11-year-old children born with a complete unilateral cleft lip and palate were examined to determine the frequency and the extent of changes in the tympanic membrane and the middle ear function and compared with 16 healthy children of the same age. The incidence of hearing impairment, abnormal middle ear pressure, retraction of the pars flaccida and abnormal tympanic membrane appearance were 24, 44, 23 and 67% respectively among the patients while the same parameters in the control group were 0, 12.5, 6 and 12%. Previous grommet insertion in the patient group was statistically correlated to both tympanic membrane abnormality and abnormal middle ear pressure but, remarkably, no association was found between grommet insertion and hearing impairment. The poor middle ear function in the children with cleft lip and palate was probably a result of reduced Eustachian tube function. PMID- 1505085 TI - Post-tonsillectomy bacteraemia. AB - Post-tonsillectomy bacteraemia is a well recognized aetiological factor in streptococcal endocarditis. Prophylactic penicillin has been recommended to reduce its incidence in susceptible patients undergoing tonsillectomy. Recent studies have shown a change in the microflora and an increase in the number of penicillin resistant organisms in the tonsils of patients undergoing tonsillectomy. The aim of this study has been to assess the incidence of post tonsillectomy bacteraemia, identify the organisms associated with it and review the suitability of penicillin in prophylactic regimens. Of the 32 patients included in the study, 11 (34.4%) had positive post-tonsillectomy blood cultures. We were surprised at this low incidence of bacteraemia and have postulated a possible reason. Haemophilus influenzae was isolated from 4 (36.4%) of the positive cultures and Streptococcus viridans in only 1 (9%). Rather than using penicillin for prophylaxis a beta-lactamase stable antibiotic would be more appropriate. PMID- 1505087 TI - Why patients fail to attend for ENT operations: a one-year prospective audit. AB - A substantial proportion of patients summoned for routine ENT operations simply fail to turn up on the day of admission. Lacking any notice, the hospital has little prospect of finding replacements, with a consequent waste of resources. A one-year prospective study has tried to identify the potential defaulters and sought their own reasons for non-attendance. All patients (n = 181) failing to respond to invitations for admission for surgery were investigated by means of a questionnaire. Non-attenders were matched with those attenders that were listed next on the admission list. The incidence of non-attenders was significantly higher in the group aged 16 years or below. Non-attenders were more likely to be male, on a longer waiting list (P less than 0.05) and listed for nasal septal operations. One in five who failed to attend had changed their address while on the waiting list. The duration of notification appeared not to influence the rate of non-attendance. PMID- 1505086 TI - Magnetic resonance imaging of the parotid gland using the STIR sequence. AB - The object of this study was to determine the efficiency of the short tau inversion recovery (STIR) sequence in the assessment of salivary disease. Sixteen patients with tumours either in or adjacent to the parotid gland were imaged using a 1.5T Philips Gyroscan, with a standard head coil. T1-weighted spin-echo and STIR sequences were obtained in multiple planes and assessed independently by each of the authors. Positive fine needle aspiration cytology or histological proof of the nature of the imaged lesions was obtained for every patient. T1 weighted spin-echo images were most useful for visualizing anatomical structures and for identification of the facial nerve. All lesions were visible with T1 weighted images but were very much more conspicuous in the STIR sequences, for which a minimal lesion resolution of 6 mm was achieved. No contrast enhancement was required. It was not possible to determine the pathological nature of the lesion by scan appearance only. Our conclusion is that a combination of T1 weighted spin-echo and STIR sequences in the axial and coronal planes is the preferred protocol for salivary gland imaging. PMID- 1505088 TI - Management of facial synkinesis with Clostridium botulinum toxin injection. AB - Associated movements after facial paralysis (synkinesis), due to unphysiological co-innervation of the facial muscles, often complicates the rehabilitation of patients following facial palsy. Clostridium botulinum toxin is a neurotoxin that interferes with the release of acetylcholine from motor nerve end plates, causing skeletal muscular paralysis. This paper concentrates on its clinical use in treating synkinesis affecting orbicularis oculi function and documents the results of treatment in 4 patients. Control of synkinesis, achieved in all 4 patients, was effective within a few days and lasted for 4-6 months. 2 patients developed transient diplopia and ptosis shortly after injection. However, no lasting complications or systemic side-effects were noted. All patients reported a significant improvement in their symptoms and reinjection at 7 months was carried out successfully. PMID- 1505089 TI - Differential diagnosis and treatment of psychogenic voice disorder. AB - Forty consecutive patients with psychogenic voice disorder were studied prospectively to shed light on some problems of differential diagnosis met by the otolaryngologist. The females (n = 35) were on average younger than males (n = 5) (mean age 34.5 vs 51.8 years, respectively). Although an upper respiratory tract infection preceding the voice disorder was reported by no more than 25% of the patients, as many as 40% had been treated with antibiotics on one or more occasions. Other treatment and voice rest had been prescribed to a further 20% of the patients. The frequency rate of reported asthma/allergy-like symptoms (37.5) exceeded the incidence of asthma/allergy in the normal Swedish adult population. Minor laryngeal abnormalities found in 10 patients could be rejected as causative since they were inconsistent with the voice disturbance. In most of the patients (n = 27), vocal function returned to normal or improved after voice therapy combined with counselling. Vocal abnormalities remained unchanged in three patients. The patients who required multiple therapy sessions (n = 10) were older (mean age 48.8 years) and seemed to have more profound personal problems than the average. The findings suggest that psychogenic voice disorder may often be misdiagnosed as acute laryngitis or asthma/allergy. Restricted use of antibiotics and other drugs is to be recommended in the treatment of benign voice disorders. PMID- 1505090 TI - A randomized study to compare calcium sodium alginate fibre with two commonly used materials for packing after nasal surgery. AB - A prospective randomized study was undertaken to compare the qualities of calcium sodium alginate (Kaltostat), trousered paraffin gauze, and glove finger packs as nasal packing material following the operation of partial inferior turbinectomy. All three types of packing material were found to be similarly effective in preventing bleeding whilst the packs were in situ. Calcium sodium alginate (Kaltostat) was associated with significantly less bleeding on pack removal than the other two packing materials. Further, irrespective of the material used, leaving the packs in situ for 48 hours produced significantly less bleeding than when they were removed after 24 hours. PMID- 1505091 TI - Intra-tympanic injections in the treatment of tinnitus. AB - Prolonged reduction or abolition of tinnitus has been reported in about two thirds of patients treated with a single or weekly-repeated injection through the tympanic membrane of either dexamethasone or lignocaine. In a small-scale trial of these treatments, dexamethasone gave 6 patients little benefit but few side effects. Lignocaine gave 5 patients no lasting benefit but violent vertigo for several hours. A. Axelsson (personal communication) had similar experience with 6 patients treated with intra-tympanic lignocaine. It is concluded that this form of treatment does not seem sufficiently effective to offset its low acceptability. PMID- 1505092 TI - Hypoxia in sleeping children: overnight studies can be reduced to 4 hours without loss of clinical significance. AB - Twelve recordings of overnight pulse oximetry representing a range of severity of obstructive sleep disturbance were evaluated by 7 experienced clinicians. Each recording was then scored by counting the number of minutes in each hour affected at any time by a fall in saturation to below 90%. Comparison of the clinical evaluation and the overall scores gave a clear level of 5 minutes per hour at and above which all the assessors agreed that the charts had clinically important desaturation. Overnight pulse oximetry was then performed on 25 children aged between 12 months and 10 years about to undergo adenotonsillectomy. The charts were scored by the method above with a score of 5 or more indicating a positive result for hypoxic episodes. The scores for shortened analysis periods of 1, 2, 3 and 4 hours duration were compared with the overall score and no cases which were negative, up to and including 4 hours, became positive in the overall result. Thus recording pulse oximetry for 4 hours provides sufficiently accurate information for clinical purposes. PMID- 1505093 TI - Effect of irradiation on middle ear effusion due to nasopharyngeal carcinoma. AB - The management of middle ear effusion by myringotomy and insertion of ventilation tubes in 75 adult patients was evaluated. In Group 1 the middle ear effusion was not related to nasopharyngeal carcinoma. The patients with nasopharyngeal carcinoma were subdivided into pre and post-radiotherapy groups (Group 2 and Group 3) according to the time of insertion of the ventilation tubes. Myringotomy and insertion of ventilation tubes achieved significant hearing gain in all three groups. The pre and post-radiotherapy groups had a higher post-operative infection rate than Group 1 (P greater than 0.01). The duration of a persistent tympanic membrane defect in the post-radiotherapy group was significantly longer than Group 1 (P = 0.03). The post-radiotherapy group had more perforations than Group 1 (P = 0.02). A total of 28% of ears in the post-radiotherapy group were discharging at the last visit. In view of the higher complication rate in the post-radiotherapy group, the role of myringotomy and insertion of ventilation tube is reassessed. PMID- 1505094 TI - A review of clinical trials regarding treatment of acute otitis media. AB - A survey was made of the English language literature on clinical trials of therapy in acute otitis media. The articles were analysed systematically for 24 parameters related to study design. We retrieved 50 studies published between 1965 and 1989. Surprisingly, the combination of a double-blind method, clearly defined inclusion criteria, and criteria for outcome was found in only 13 studies. Most of these 13 compared different antibiotic regimens and only 4 were placebo-controlled. A recommendation based on the conclusions reached can, even in these 13 studies, hardly be obtained due to failure to show an overall difference in favour of a specific treatment regimen. Our study shows that many trials are methodologically flawed which makes it difficult to accept their results. In view of current controversy on management of acute otitis media, well conducted placebo-controlled clinical trials are still needed. PMID- 1505095 TI - What is the best method of treatment for labyrinthine fistulae caused by cholesteatoma? AB - A series of 19 patients with a labyrinthine fistula caused by cholesteatoma was analysed. Two patients presented with acute suppurative labyrinthitis and meningitis. A canal wall down procedure was performed in all but one patient. Of the 17 patients with preserved inner-ear function, the cholesteatoma matrix over the fistula was removed in 10 resulting in severe sensorineural hearing loss in one of these. The matrix was left in situ in 7 patients and hearing was maintained or improved in all of them. Post-operatively, 2 patients suffered from vestibular disturbances, the matrix covering the fistula being removed in both of them. It was concluded that preservation of the matrix over the fistula is the safest method of management of this serious complication of cholesteatomatous chronic ear disease. PMID- 1505096 TI - A dynamic and natural frequency analysis of the Fisch II spandrel using the finite element method. AB - The recent introduction of the Fisch II spandrel total ossicular replacement prosthesis (TORP), has provided impressive initial hearing benefits in patients. The design, based on a combination of soft plastic and a highly flexible metal shaft, has been analysed in terms of its sound collecting and conducting behaviour using the finite element method. The analysis has examined the mode shapes, displacements and natural frequencies of the prosthesis for a variety of material properties and geometries. The results indicate the optimum vibration characteristics are obtained with a Polycell elastic modulus of 100 N/mm2, with the natural frequency independent of modulus above this value. Furthermore, the diameter of the spandrel shaft is crucially important, with an increase in magnitude of the first natural frequency of 54% for a 25% increase in shaft diameter. At a Polycell membrane thickness of 0.07 mm and a shaft diameter of 0.12 mm, the tympanic membrane and Fisch II prosthesis have almost identical frequencies over the 1st to 6th frequency range. This fact, together with the flexibility of clinical procedures involved in its use, may be the reason for its success. PMID- 1505097 TI - A prospective study of otitis media with effusion in adults and children. AB - A prospective study of otitis media with effusion (OME) in both adults and children has been carried out. 75 new adult patients were seen during a 4-year period. Of these, 13 had associated diseases which could reasonably be considered to have been a cause of their effusion. Over a 2-year period, 192 new children with OME were seen. There was a significantly higher incidence of previous otalgia and/or aural discharge in the children as compared to the adults (P less than or equal to 0.001). The adults had significantly more serous effusions than the children (P less than or equal to 0.001), but both mucoid and serous effusions occurred in both groups. Similar rates of spontaneous resolution were observed in the 2 groups. Within the adult group, patients with a history of upper respiratory infection at the onset of hearing loss were significantly more likely to have spontaneous resolution of their effusion (P less than or equal to 0.02). PMID- 1505098 TI - Hearing with the bone-anchored hearing aid (BAHA, HC 200) compared to a conventional bone-conduction hearing aid. AB - Sixteen patients have been fitted with a standard bone-anchored hearing aid (HC 200), to replace their conventional bone-conduction aid. The average pure tone threshold at 0.5, 1 and 2 kHz varied from 35 to 75 dB HL, with a sensorineural component varying from 0 to 30 dB HL. The patients' performance with the bone anchored aid was compared to that with the conventional bone-conduction aid in an acoustic-free field. The maximum phoneme score in quiet was 100% in most patients; in 6 patients, the score with the bone-anchored aid was better (range from 5 to 10%). The speech-in-noise ratio was significantly better in 11 patients (range from -1.4 to -8 dB). None of the patients had poorer results on either test with the bone-anchored aid. The improved speech recognition was ascribed to better performance of the hearing aid in the higher frequency range (above 2 kHz) and to relatively less distortion. PMID- 1505099 TI - Small cavity mastoidectomy. AB - Disappointment with the long-term results of closed operations for ears with extensive cholesteatoma has led to a renewed preference for open techniques. Although the technical advantages provided by magnification and hypotensive anaesthesia have reduced the numbers of unstable post-operative open mastoidectomy cavities, when large, they are still frequently troublesome. Frequently, surgical cavities have been much larger than necessary because of adherence to a traditional approach to the pathologic lesion from its posterior aspect, and the inevitable removal of much normal bone. It is proposed herein that if, instead, bone removal were commenced from the area proximate to the origin of the disease and extended only as far as necessary in order to achieve adequate and effective exteriorization of the disease, fewer large cavities would result and the proportion of stable post-operative ears would be increased. To test this, 100 patients have been treated by atticoantrotomy in which bone lateral to the cholesteatoma sac was removed from anterior to posterior. The 5 year status of the first 43 patients thus treated supports the view that atticoantrotomy provides a logical, safe and successful means of treating extensive cholesteatoma. PMID- 1505100 TI - Results of surgery for chronic otitis media in patients with a cleft palate. AB - The long-term results of surgical treatment of 19 chronic ears in 16 patients with a cleft palate were analysed. The mean follow-up period was 6.5 years. The patients were found to be significantly younger than other patients with chronic otitis media. Granulating otitis media was the indication for surgery in 11 ears and cholesteatoma in 7 ears. A successful outcome after the primary operation was found in 68% of the patients. Four patients required a revision operation which was successful in all of them. Hearing results of patients with cleft palate did not differ significantly from those obtained in other patients. It is concluded that middle ear surgery should be offered to patients with a cleft palate with the same indications as in other patients with chronic otitis media. PMID- 1505101 TI - The role for epidemiology in rheumatology. PMID- 1505102 TI - Type II collagen induced arthritis: comparison of histological changes in arthritis-susceptible and arthritis-resistant rats. AB - Wistar rats (type II collagen-induced arthritis-susceptible) and PVG.RT1u rats (arthritis-resistant) were immunised with type II collagen and histological changes in the synovial tissues of the hind feet and in the popliteal lymph nodes draining these feet were examined and compared with unimmunised rats. There were no apparent differences in the joints of unimmunised rats of each strain, but the popliteal lymph nodes of the Wistar rats appeared more "activated", suggesting possible differences between strains in the continuous, low-grade release of antigens from the joints. Whilst the joints of arthritic rats showed the most marked histological changes, the joints of immunised PVG.RT1u rats and of non arthritic Wistar rats showed some minor changes in the synovia and loss of cartilage with a concomitant increase in the size of the popliteal lymph nodes. The number of mast cells per unit area increased in the lymph nodes of immunised PVG.RT1u rats in proportion to the size increase, but decreased in those draining arthritic Wistar rat feet. The number of mast cells per unit area of synovium decreased most in arthritic feet and the staining pattern of the mast cells altered in the most severely arthritic feet, suggesting a change in mast cell population. These differences in mast cells may be directly related to whether or not clinical arthritis develops in a particular joint. Further study of mast cell sub-populations is warranted. PMID- 1505103 TI - Synovitis equivalent to erosions in rheumatoid arthritis: implications of skeletal analysis for the clinical management of contemporary rheumatoid arthritis. AB - Examination of a contemporary skeletal collection revealed a rheumatoid subgroup with parameters mirroring those of contemporary clinical populations. This rheumatoid population was also indistinguishable from contemporary (live) clinical populations, on the basis of the actual distribution of radiologically detectable erosions, thus validating its representativeness. Gross examination of these defleshed skeletons allowed assessment of the significance of erosive disease in rheumatoid arthritis. As anticipated, the frequency of visibly detectable erosions exceeded that detectable radiologically. The frequency of visibly detectable erosions, however, was indistinguishable from the frequency of synovitis in clinical populations. The excellent correlation of the gross and clinical distribution of disease suggests that some degree of erosive disease is integral to all lesions of rheumatoid arthritis and that only the relative insensitivity of radiologic techniques precludes universal recognition of those erosions. This work suggests that any therapeutic intervention which settles for only partial synovitis control will not prevent the progression of erosive disease; and perhaps explains the difficulty of demonstrating alterations in erosion progression in studies of disease modifying agents. PMID- 1505104 TI - Interferon-gamma increases human neutrophil-mediated cartilage proteoglycan degradation. AB - Interferon gamma (IFN-gamma) is known to activate neutrophils and is produced by the synoviocytes, macrophages, T cells and other inflammatory cells in rheumatoid arthritis. Neutrophils participate in articular cartilage destruction and predominate in the synovial fluid of inflamed joints during the early stages and acute exacerbations of the disease. In this study we investigated the effect of recombinant human IFN-gamma on human neutrophil damage to bovine articular cartilage explants which had been coated with heat-aggregated IgG (HAGG). Cartilage proteoglycan degradation by neutrophils was augmented by IFN-gamma at 10(2)-10(4) U/ml. IFN-gamma also increased neutrophil-mediated proteoglycan degradation when the cells were preincubated with IFN-gamma and washed before addition to cartilage. This activity of IFN-gamma was abolished by boiling and was unaffected by polymixin B, indicating that the effects of IFN-gamma were not due to endotoxin contamination. In the absence of neutrophils IFN-gamma had no effect on proteoglycan metabolism, and the ability of IFN-gamma to increase neutrophil-mediated proteoglycan degradation did not require living chondrocytes. Adherence of neutrophils to HAGG-coated and uncoated cartilage explants was enhanced by IFN-gamma. Opsonisation of the cartilage with HAGG also increased the adhesion of neutrophils. In contrast to the enhancement of neutrophil-mediated proteoglycan degradation, IFN-gamma had no effect on the inhibition of proteoglycan synthesis by neutrophils. PMID- 1505105 TI - Elimination diet in the treatment of selected patients with hypersensitivity vasculitis. AB - We have evaluated the effects of an elimination diet in 5 patients with hypersensitivity vasculitis and a personal or family history of allergy. The presence of autoimmune disorders, infections and neoplastic diseases was excluded on the basis of physical examination, clinical history and laboratory data. Three patients had elevated serum immune complexes and evidence of complement consumption before the oligoantigenic diet. In one patient food allergy was diagnosed on the basis of a positive and concordant challenge test, skin prick test and RAST. The study consisted of a 3 week elimination diet, followed by open and double blind challenge tests with specific foods and additives. Four patients achieved a complete remission and one patient experienced great improvement on the elimination diet. In three cases the vasculitis relapsed following the introduction of food additives; in one case with the addition of potatoes and green vegetables (i.e., beans and green peas) and in the last case with the addition of eggs to the diet. The offending foods and additives were subsequently eliminated from the usual diet and no relapses were observed in 2 years of follow up. These results show that in selected patients with a history of allergy, hypersensitivity vasculitis can be triggered and sustained by food antigens or additives. PMID- 1505107 TI - Type II collagen-immune complex arthritis in sheep: collagen antibodies in serum, synovial fluid and afferent lymph. AB - Type II native bovine collagen was used to induce arthritis in sheep. The sheep received a subcutaneous injection of collagen in Freund's adjuvant, and some sheep also received an intra-articular injection of collagen. The response to the collagen injections was monitored by measurement of antibody levels to bovine and ovine collagen in serum, synovial fluid and afferent lymph samples. There were antibodies in the normal sheep serum which reacted with native and denatured type II collagen, but there was a marked rise in serum and synovial fluid reactivity after subcutaneous injection of native collagen. In these sensitised sheep there was a further rise in antibody levels in the synovial fluid and afferent lymph samples after an intra-articular injection of collagen. There was little effect on antibody levels in the non-injected contralateral limb. Histological and immunohistochemical studies showed that the rise in antibody levels was associated with pathological changes to the synovium which were consistent with the development of arthritis. These changes were most severe in those joints of sensitized sheep which had received an intra-articular injection of collagen and were characterized by increased numbers of T cells in the synovial tissue, mainly of the CD4 phenotype. There was a marked increase in B cell expression by cells on the surface of the synovial intima, and accumulations of B and T cells were seen in the subsynovial tissues. Collagen-immune complex arthritis in sheep appears to be a useful large animal model of arthritis, with significant similarities to the arthropathies of other species, including man.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1505106 TI - Production of neutrophil activating peptide-1 (NAP-1/IL-8) by blood and synovial fluid mononuclear cells from patients with arthritis. AB - As polymorphonuclear leukocytes (PMN) are predominant in inflammatory synovial fluids, we investigated the production of neutrophil-activating peptide-1 (NAP-1) by mononuclear cells (MC) from 15 synovial fluids and matched peripheral blood. MC were cultured for 24 h alone or with stimulants (ConA, LPS). NAP-1 was determined in the supernatants by a bioassay (elastase release from normal human PMN) and an immunoassay (sandwich ELISA with a mouse anti-NAP-1 mAb and an alkaline phosphatase labelled goat anti-NAP-1 pAb). The results showed a significant increase in NAP-1 production by synovial fluid MC when compared to peripheral blood MC. Both cell types produced more NAP-1 in the presence of added stimuli. The results obtained with the two methods of detection were in close agreement. No relationship was found between the amount of NAP-1 produced in 24 h and the number of synovial fluid leukocytes, the erythrocyte sedimentation rate, the diagnosis of the underlying arthritis or the treatment of the patients. PMID- 1505108 TI - Proteoglycan structural changes in human rheumatoid articular cartilage. AB - Human rheumatoid arthritic (RA) cartilage contains elevated levels of proteolytic enzymes in which the metalloproteases are believed to be the prime enzyme system involved in cartilage metabolism. We examined the effects of these enzymes and the serine proteases on endogenous proteoglycans (PGs) and newly synthesized PGs of seven RA cartilages. The data was further analyzed with regard to the therapy received by the patients prior to surgery. A structural heterogeneity among the PGs from RA cartilage was found, and two subsets were distinguished. While in the first subset more than 35% of the PGs were in aggregate form, no appreciable amount of PG aggregate was found in the second subset. Interestingly, in all but one specimen the subsets appeared to be a function of prior therapy received by the patients. In subset I patients had received prednisone and/or DMARD in addition to NSAIDs, while those from subset II had all received NSAIDs only, with one exception. Our findings also suggest that PG structure alterations could result from the action of already active and APMA-activated metalloproteases; these reduced the PG aggregation capability and caused extensive cleavage in the PG core protein. The serine proteases did not seem to play a major role. Moreover, when the endogenous latent metalloproteases were activated with APMA, high-density PGs (the A1D1 fraction) showed a reduction in their capacity to reaggregate, and in their hydrodynamic size. Using an immunological technique we demonstrated the presence, in subset I, of the hyaluronan binding region domain (HABR) of the core protein. For subset II this domain could not be found.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1505109 TI - Anticardiolipin antibodies in a patient with Crohn's disease and thrombosis. AB - Thrombosis is an uncommon though well recognized complication of inflammatory bowel disease, for which various coagulation alterations have been described as possible causes. Antiphospholipid syndrome (APS) is defined as the association of thrombosis, fetal loss and thrombocytopenia with anticardiolipin antibodies (aCL) and/or lupus anticoagulant (LA). We describe a case of a 21-year-old female with recurrent thrombosis associated with aCL who went on to develop Crohn's disease. Tissue typing done in this patient revealed the presence of the HLA-DR7, DRw53, which previous studies have shown to be found in increased frequencies in APS patients. To our knowledge, this is the first report of an association between these two clinical conditions and, in this particular case, aCL may be implicated in the thrombotic events. PMID- 1505110 TI - Tenosynovitis due to Mycobacterium avium-intracellulare: case report and a review of the literature. AB - A 57-year-old female patient presented with a tenosynovitis due to Mycobacterium avium-intracellulare (MAI). A relapse occurred following surgical treatment, after which she was successfully treated with ansamycin and ethambutol. Previously reported cases of tenosynovitis due to MAI are reviewed and the treatment modalities are discussed. PMID- 1505112 TI - Atypical Behcet's disease with peripheral erosive arthropathy and pyoderma gangrenosum. AB - We report a 52-year-old male Caucasian who presented with a peripheral erosive arthritis, then pyoderma gangrenosum, and six years later pancolitis and orogenital ulcers. The case illustrates an overlap that may exist between Behcet's syndrome and inflammatory bowel disease. In either condition seronegative erosive peripheral joint disease is an uncommon presenting feature. PMID- 1505111 TI - Intravenous corticosteroid therapy of cervical cord compression in rheumatoid arthritis. AB - We describe a case of atlantoaxial joint subluxation and cervical myelopathy in a patient with rheumatoid arthritis. Magnetic resonance imaging (MRI) demonstrated a large periodontoid pannus compressing the upper cervical cord. Neurological function improved rapidly after treatment with intravenous pulse corticosteroids given before surgical fusion of the cervical spine. Post operative MRI showed a significant reduction in size of the pannus. PMID- 1505113 TI - Human platelets in synovial fluid. A focus on the effects of growth factors on the inflammatory responses in rheumatoid arthritis. AB - The alpha granules of platelets are a major storage site for peptide growth factors. The inflamed synovial fluid of rheumatoid arthritis contains a high number of platelets as well as platelet-derived growth factors. These platelets may apparently be acted upon to release their alpha granule-located substances. It can thus be suggested that platelets present in the synovial fluid express growth factors of significance to the local inflammatory responses of rheumatoid arthritis. PMID- 1505114 TI - Increased frequency of DR4 in systemic onset juvenile chronic arthritis. AB - Eighty-one patients with systemic onset juvenile chronic arthritis (JCA) have been tested for HLA-A, -B, -C, and -DR antigens. This study confirms previous reports of an increased incidence of DR4 in these patients. Subdivision of the patients according to their disease course over ten years showed different HLA associations with different disease courses. The frequency of DR4 tended to be greater in patients with less severe disease. There was also an increased incidence of HLA B27 in patients in whom relapses of disease were associated with intercurrent infections. PMID- 1505115 TI - The correlation between immunoglobulin levels and disease activity in juvenile chronic arthritis. PMID- 1505116 TI - Soluble interleukin-2 receptor in systemic lupus erythematosus--relationship to disease activity and kidney function. PMID- 1505117 TI - The role of iron, vitamin B12, folic acid and erythropoietin in the anemia of rheumatoid arthritis. PMID- 1505118 TI - Nerve growth factor and distribution of mast cells in the synovium of adult rats. PMID- 1505119 TI - The beta-2-glycoprotein I and antiphospholipid antibodies. AB - Beta 2-GPI is a single chain, 50 kd glycoprotein made up of 326 amino-acids, present in human plasma at concentrations of about 200 micrograms/ml. It has been shown to represent the "serum cofactor" important in determining the binding of aCL to phospholipids both in fluid and in solid phase assays. Its cofactor activity is demonstrable for aPL antibodies from patients with autoimmune but not with infectious diseases. It is immunogenic in heterospecific models, and immunization with beta 2-GPI seems to be able to induce the production not only of anti-beta 2-GPI but also of aPL antibodies. Most probably its binding to CL changes the configuration of phospholipids to a more immunogenic one. The various characteristics of beta 2-GPI are summarized in Table I. beta 2-GPI has been recognized as a natural anticoagulant protein, but its possible role in the pathogenesis of the APLS remains to be determined. PMID- 1505120 TI - Isolation and characterization of a low metastatic variant from EL-4 mouse T lymphoma. AB - A variant cell line (EL-4ad) which adhered to a tissue culture dish was isolated from highly metastatic EL-4 murine T-lymphoma. The experimental and spontaneous metastatic ability of EL-4ad was lower than that of the EL-4 parent cell line. The cell surface phenotypes of both cell lines were CD2+3+4-8-45+TCR alpha beta+TCR gamma delta-, but the level of CD2 expression of EL-4ad was much lower than that of EL-4. Furthermore, EL-4ad had higher binding ability to fibronectin and expressed more PNA receptors on the cell surface than EL-4. These differences indicated that either the maturation stage of the less metastatic variant was lower than that of the parent cell line or the activation state of the two cell lines differed. EL-4ad showed higher in vitro invasiveness and adhesiveness to liver cells, and these characters were not consistent with the reduced metastatic ability of this variant. Neuraminidase-releasable cell surface sialic acid levels did not differ significantly between the cell lines. Neither cell line was adhesive to laminin, type IV collagen or reconstituted basement membrane. These metastasis-related properties could not explain the decreased metastatic ability of EL-4ad. On the other hand, EL-4ad was more sensitive to NK activity than EL-4 in vivo, and this was thought to be a major cause of its decreased metastatic ability. The molecules or mechanisms involved in the differentiation or activation of T-cells may be responsible for the sensitivity of tumor cells to NK activity. PMID- 1505121 TI - Calcium depletion reduces the destruction of fibrosarcoma cells in the microvasculature of artificially perfused rat hearts. AB - Earlier studies have shown that most tumour cells (TCs) injected into the circulation die rapidly. The mechanisms behind this rapid elimination of TCs are not known, but some experimental data suggest that mechanical trauma to the cells in the capillary bed plays a role. In the present investigation 725,000 rat fibrosarcoma cells (250,000/ml) were infused into the coronary microcirculation of isolated and artificially perfused (flow rate approx. 6 ml/min), beating and non-beating (Ca2+ excluded from the perfusate) rat hearts. The analyses included calculations of the number of TCs retained in the myocardium 5 min after start of TC infusion and their distribution within the ventricular wall. In addition, ultrastructural studies were performed to identify possible structural changes of trapped TCs and myocardial tissue. Intact and viable TCs in the effluent perfusate were counted. In beating hearts about 20% of the infused TCs were collected microscopically intact after passage through the heart circulation, and of these cells only 32% were viable (in-flow viability 87-91%). In Ca(2+) depleted hearts the corresponding figures were 29 and 48%, respectively. The difference in viable cell counts was statistically significant (P less than 0.001). The TCs trapped in the left ventricular wall of the myocardium of beating hearts were mainly found in the subepicardial third of the wall, whereas in non beating hearts the trapped cells were distributed randomly. The ultrastructural appearance of trapped cells differed between the two groups: 82% of cells trapped in beating hearts showed signs of severe damage, with subcellular vacuolization and plasmalemmal disruption, whereas 65% of cells trapped in Ca(2+)-depleted hearts seemed undamaged with intact cell membranes and cytoplasmic organization. The remaining 35% showed variable subcellular disorganization. The results cannot entirely be explained by mechanical TC damage in the microcirculation due to intracapillary deformation. The observations require additional explanatory mechanisms. One possible important TC damaging mechanism, dependent on extracellular Ca2+ levels, could be endothelial cell release of reactive oxygen species. PMID- 1505122 TI - Murine Kupffer cells and hepatic natural killer cells regulate tumor growth in a quantitative model of colorectal liver metastases. AB - This investigation aimed to develop a biologically relevant murine model of colorectal liver metastases and determine if Kupffer cells (KC) and hepatic natural killer cells (hNKC) regulate tumor growth. The model involves the injection of murine colon adenocarcinoma 26 (MCA 26) tumor cells into the portal vein of female-specific pathogen-free BALB/c mice. Metastases developed in all animals, and the growth was limited entirely to the liver. To determine if KC and hNKC control the development of liver metastases, the in vivo function of these hepatic effector cells was modulated. Tumor growth was quantitated by the uptake of 125I into tumor DNA. Stimulation of the KC and hNKC produced a significant (P less than 0.01) dose-dependent decrease in 125I uptake in the liver in both treatment groups, which was associated with a significant improvement in survival (P less than 0.05). The in vivo cytotoxic function of the liver was inhibited with an intravenous injection of gadolinium chloride (for KC) or asialo GM1 antiserum (for hNKC). Inhibition of KC and hNKC cytotoxic function led to a significant (P less than 0.01) increase in 125I uptake in the liver and a significant decrease in survival (P less than 0.05). PMID- 1505123 TI - Breast carcinoma: periodicity in presentation of metastatic tumour growth in the axilla. AB - The clinical value of assessment of tumour load in the axilla in the treatment of breast cancer patients has stood the test of time. Much information is available on its extent and characteristic distribution but, in contrast, little is known of the biological factors that may control the timing of the metastatic phenomenon. There is recent circumstantial evidence that such factors may exist and this prompted the present detailed study of axillary metastases from a series of 437 consecutive cases of breast carcinoma. Evidence of such factors was found here also: the excess of micrometastases in cases coming to operation in the second half of the year was highly significant (P less than 0.001) and is consistent with a synchronized start to the metastatic process. The total metastatic pattern in the material further indicated that the process may show periods of inactivity, i.e. periods when new colonies are not recruited. Mechanisms controlling this periodicity could theoretically be light-mediated, opening up new possibilities in the development of anti-metastatic treatment regimes. PMID- 1505124 TI - Identification of intracranial liqor metastases of experimental stereotactically implanted brain tumors by the tumor-selective MRI contrast agent MnTPPS. AB - Two cases of stereotactically induced and spontaneously metastasizing neoplasms in the rat and the cat brain are reported. In the rat, a malignant Schwannoma derived from initially supratentorially implanted RN6 cells developed a second tumor in the posterior cranial fossa. In the cat, a highly malignant polymorphous anaplastic glioma induced by implantation of cloned rat glioma cells (F98) into the left internal capsule developed small tumor cell nests along the ependyma of the ipsilateral ventricle. In precontrast magnetic resonance imaging (MRI) of both cases, the primary tumor was detectable only by a very weak hypointensity and through a shift of the midline. No metastases were apparent. Application of the metallated paramagnetic porphyrin derivative manganese(III) tetraphenylporphine sulfonate (MnTPPS) resulted in a remarkable contrast enhancement between tumoral and normal tissue, which was evident not only in the primary tumor but also in the small metastases. These observations demonstrate for the first time that MnTPPS is an efficient MRI contrast agent for the detection of metastases from primary brain neoplasms and, in consequence, support the hypothesis of its selective binding to tumor cells. PMID- 1505126 TI - Unsuspected meningitis diagnosed by In-111 labeled leukocytes. A case report. AB - Clinically unsuspected bacterial meningitis was found in a patient with fever of unknown origin. Blood and urine cultures were negative for growth. Chest radiography and abdominal CT were negative for infection. Triple-phase bone imaging was performed to rule out osteomyelitis from a gunshot wound. A left posterior iliac crest hot spot may have represented osteomyelitis, but In-111 labeled leukocyte imaging instead disclosed unsuspected meningitis. The CSF culture after the imaging was positive for Enterobacter aerogenes. PMID- 1505127 TI - Renal scintigraphy in a patient with pelvic lipomatosis. AB - A patient with a history of benign prostatic hypertrophy and pelvic lipomatosis was evaluated for pain and swelling of the abdomen and left leg. As part of his workup, renal imaging was performed and revealed medial deviation of the ureters, incomplete emptying of the collecting systems, and a pear-shaped bladder. Although these findings have been reported with other imaging modalities in patients with pelvic lipomatosis, they have not been described in renal scintigraphy. This constellation of findings should lead to the consideration of the diagnosis of pelvic lipomatosis. PMID- 1505125 TI - NIH3T3 transfectant containing human K-ras oncogene shows enhanced metastatic activity after in vivo tumor growth or co-culture with fibroblasts. AB - A clone of NIH3T3 transformant (H-3), obtained by transfecting genomic DNA of a human colon carcinoma cell line, contains human K-ras oncogene and yields metastatic pulmonary nodules after intravenous injection of the cells into nude mice. This metastatic ability was enhanced remarkably after in vivo tumor growth (subcutaneous tumor formation in nude mice) accompanied by increased mRNA expression and gene amplification of the human-derived K-ras oncogene, while it declined gradually as the passage number increased in vitro, with corresponding decreases of gene amplification and mRNA expression. Six subclones were randomly selected from H-3 cells which had been subcultured to passage 22. All of the clones in culture showed almost the same low level of metastatic ability and exhibited little K-ras oncogene amplification with correspondingly low mRNA expression. However, after they formed tumors in nude mice, every clone acquired high metastatic ability and the gene amplification increased, with elevated mRNA expression. These experimental facts indicated that acquisition of metastatic ability coupled with the function of K-ras oncogene was conditional in nature, being strongly affected by in vivo tumor circumstances. The low metastatic and G 418-resistant H-3 cells were co-cultured with BALB/c3T3 fibroblasts for 2-4 weeks. After removal of fibroblasts by exposure to G-418, the tumor cells exhibited increased metastatic ability and human K-ras oncogene mRNA, suggesting an intimate interaction between H-3 cells and fibroblasts influencing the function of transfected human K-ras oncogene. Fibroblasts of the host animal may thus have an important role in generating enhanced metastatic activity of H-3 cells. PMID- 1505128 TI - Transient diaphyseal tibial Tc-99m MDP uptake and bone marrow edema in acute rheumatic fever. AB - The authors describe a patient with acute rheumatic fever and polyarthritis in whom scintigraphy unexpectedly identified Tc-99m MDP uptake in the diaphyses of both tibiae. A dramatic rise in antistreptolysin-O titer and rapid resolution of tibial abnormalities paralleled marked articular improvement. Magnetic resonance imaging demonstrated a pattern consistent with marrow edema in the area of abnormal Tc-99m MDP accumulation. This finding has not been previously described in acute rheumatic fever, and it was suspected that the changes in the tibiae resulted from subclinical diaphyseal hyperemia from the inflammatory process observed in the contiguous joints. PMID- 1505129 TI - Bilateral testicular neuroblastoma. Scintigraphic depiction and therapy with I 131 MIBG. AB - The authors describe a 29-year-old man who had a 16-year history of neuroblastoma and uncommon manifestations. At age 13, he was diagnosed with stage III retroperitoneal ganglioneuroblastoma that was resected. Ten years later, bilateral testicular enlargement and a pelvic mass from infiltration of the neuroblastoma became palpable. Metastatic involvement was depicted with MIBG, a radiotracer that concentrates in tissues of the sympathetic nervous system. Using I-131 MIBG, the tumors were treated with therapeutic doses of radiation and a partial response was obtained. This case is unique because of the massive degree of bilateral testicular infiltration and its occurrence as a late manifestation of neuroblastoma in early adulthood. PMID- 1505130 TI - Functional studies of left upper quadrant mass aid management of idiopathic thrombocytopenic purpura. AB - ITP (idiopathic thrombocytopenic purpura) causes rapid sequestration and destruction of thrombocytes by the spleen, liver, bone marrow, and reticuloendothelial elements of other organs. The usefulness of multiple radionuclide functional imaging procedures in the management of a 34-year-old woman with chronic ITP, two splenectomies (removal of the initial spleen and then a hypertrophied accessory spleen), and the failure of chemotherapy to control her thrombocytopenia, are discussed. A combination of In-111 oxine autologous platelet imaging, liver/spleen imaging, disofenin (liver/gallbladder) imaging, and glucoheptonate renal imaging demonstrated that her platelets were being sequestered by a markedly enlarged left hepatic lobe extending to the left lateral wall, with a small amount in the kidneys and lungs, and that there was no second accessory spleen. PMID- 1505131 TI - Nonpustular psoriatic lesions detected by Tc-99m HMPAO labeled granulocytes. AB - A patient with a fever of unknown origin was evaluated by abdominal SPECT using Tc-99m HMPAO labeled granulocytes and a triple detector camera. Although no abscesses were located, nonpustular psoriatic skin lesions were demonstrated incidentally on the reprojectional images. Psoriatic scales contain a chemotactic factor for leukocytes, and this is a likely explanation for the increased uptake of the radiotracer by psoriatic lesions. PMID- 1505132 TI - Progressive soft tissue uptake of Tc-99m MDP reflecting metastatic microcalcification. AB - A 49-year-old woman had longstanding renal impairment. Markedly increased uptake of Tc-99m MDP in the heart, lungs, and kidneys was an incidental finding on bone scintigraphy performed to exclude metastatic bone disease. These findings persisted on repeat bone imaging 1 year later. In addition, gastric and skeletal muscle uptake was subsequently seen. Soft tissue microcalcification was confirmed by computed tomography and renal biopsy. A consideration of the differential diagnosis is presented. PMID- 1505133 TI - Dual isotope SPECT in the evaluation of recurrent brain tumor. AB - Dual isotope brain SPECT was performed in a patient with recurrent brain tumor (grade II astrocytoma). In this case, a good coregistration of brain perfusion and tumor images was obtained because Tc-99m HMPAO and the Tl-201 chloride imaging were done simultaneously using a Triad SPECT unit. This method might play an important clinical role in the evaluation of patients with recurrent brain tumors. PMID- 1505134 TI - Effect of sympathetic blockade on bone imaging. PMID- 1505135 TI - Bone imaging and congenital hemihypertrophy. PMID- 1505136 TI - An unusual anatomic variant of viable myocardium after infarction. PMID- 1505137 TI - Cold fracture on bone imaging in secondary hyperparathyroidism. PMID- 1505138 TI - SPECT detection of pulmonary artery branch obstruction from a migrated Gianturco coil. PMID- 1505139 TI - Detection of myocarditis in dilated cardiomyopathy by Tc-99m HMPAO WBC myocardial imaging in a child. PMID- 1505140 TI - Bile leak into the lesser sac of the peritoneum. PMID- 1505142 TI - Heparin pharmacokinetics and pharmacodynamics. AB - Heparin was discovered approximately 75 years ago and has been used extensively for the last 50 years to treat thromboembolic disorders. An endogenous glycosaminoglycan, heparin is found largely in the liver, lung and intestine. It is available for exogenous administration both as unfractionated and low molecular weight heparin. Unfractionated heparin is a heterogenous mixture of polysaccharide chains of varying length resulting in a range of molecular weights from 3000 to 30,000D while low molecular weight heparin ranges from 3000 to 6000D. Heparin produces its antithrombotic effect by binding to antithrombin III and this complex then binds to thrombin. In order to accomplish this a total of 18 to 22 monosaccharide units is necessary including a specific pentasaccharide binding site for antithrombin III. After either subcutaneous or intravenous injection heparin is distributed primarily within the intravascular space. A short distribution phase is seen which is thought to correspond to endothelial cell binding and internalisation. The disposition curve for unfractionated heparin has a unique concave-convex shape which is the result of combined saturable and nonsaturable elimination mechanisms. The nonsaturable elimination mechanism is renal and is the primary route of elimination for low molecular weight heparins. For this reason, the concave-convex pattern is not seen with low molecular weight preparations. Both forms of heparin are useful antithrombotic agents; however, the correlation between the antithrombotic effect and an in vitro laboratory test for either type still needs further clarification. PMID- 1505143 TI - Pharmacokinetic optimisation of angiotensin converting enzyme (ACE) inhibitor therapy. AB - Angiotensin converting enzyme (ACE) inhibitors are increasingly used to treat hypertension and congestive heart failure. Recently, several new ACE inhibitors with pharmacokinetic features different from earlier agents such as captopril or enalapril have come into use. This review discusses the use of pharmacokinetics to optimise ACE inhibitory therapy in various patient groups. Among the pharmacokinetic characteristics of ACE inhibitors the route of excretion and to a lesser degree the half-life appear to be the most clinically relevant. There is no evidence that being a prodrug offers a significant clinical advantage. The importance of varying tissue penetration also remains to be determined. Knowledge of ACE inhibitor pharmacokinetics is particularly important in patients with renal or hepatic dysfunction in whom the major route of excretion of these agents is impaired. This might also be the case in elderly patients or those with severe congestive heart failure. However, for most ACE inhibitors, major changes in the drug dosage (amount or interval) are necessary only when the glomerular filtration rate falls below 30 ml/min (1.80 L/h). The occurrence of adverse effects due to overdosage or drug interactions may be prevented by adapting the prescription of an ACE inhibitor to its pharmacokinetic characteristics. PMID- 1505144 TI - Pharmacokinetics of factor VIII in humans. Obtaining clinically relevant data from comparative studies. AB - The pharmacokinetics of Factor VIII procoagulant activity (FVIII:C) were investigated in 10 patients receiving 2 different high purity concentrates of FVIII. The in vivo recovery of FVIII:C depended on the method of blood volume estimation and on the in vitro assay used to define the potency of the concentrate; more generally, it also depends on the study design. The use of in vivo recovery to compare FVIII preparations should therefore be discouraged and the achieved area under the FVIII activity-time curve (AUC) should be used instead. The volume of distribution at steady-state (Vss) of FVIII:C was significantly greater than the estimated plasma volume of the patients. The mean terminal half-life of FVIII:C was slightly assay-dependent, being 14h by a 1 stage clotting assay and 12h by a chromogenic assay. The calculated apparent clearance (CL) of FVIII:C, as well as the Vss and the in vivo recovery, depended on the measured in vitro potency of the FVIII concentrate. These methodological aspects of pharmacokinetic studies are of direct interest to the clinician, since the routine administration of FVIII is based on the pharmacokinetic properties of the specific preparation. PMID- 1505145 TI - Pharmacokinetic modelling of a parent drug and its metabolite. Atracurium and laudanosine. AB - A pharmacokinetic model was designed to describe simultaneously the plasma concentrations of atracurium and its metabolite laudanosine. The proposed model satisfactorily fits the observations and is based on the assumptions that the parent drug spontaneously degrades to laudanosine at the rate comparable with that observed in vitro at pH 7.4 and 37 degrees C; that 2 molecules of laudanosine are formed from 1 molecule of atracurium; that an initial very rapid decay of a fraction of the atracurium dose is responsible for the initially high plasma laudanosine concentrations; that the rapid disappearance of atracurium from plasma is accounted for by its spontaneous degradation and by the sequestration of atracurium in a deep compartment; and that laudanosine formed from atracurium is added to its central compartment, with its disposition described by a simple 2-compartment model with elimination from the central compartment. The model projects that about 43% of the atracurium dose is rapidly converted to laudanosine and that nearly the whole injected amount of atracurium is degraded to laudanosine. PMID- 1505146 TI - Publication bias: its implications for clinical pharmacology. PMID- 1505147 TI - Differing effect of atropine on heart rate in Chinese and white subjects. AB - To determine if differences exist between Chinese and white subjects in their response to atropine and if the intrinsic heart rate and the autonomic contribution to the heart differ between the two races, eight white and eight Chinese males were studied. In all subjects the heart rate decreased after the first dose of atropine (0.003 mg/kg) with no difference in the bradycardia between the two races. However, as further doses were administered, the heart rate increased in both groups, resulting in a significantly (p less than 0.05) greater increase in Chinese subjects than in white subjects. The increase in heart rate for each nanogram per milliliter of atropine was 2.8-fold higher (p less than 0.05) in the Chinese subjects (19.24 +/- 4.41 beats/min) compared with white subjects (6.83 +/- 1.62 beats/min). There was no difference in the intrinsic heart rate, in the relative vagal contribution, or in relative sympathetic contribution to the heart rate between the Chinese and white subjects. These data indicate that Chinese subjects are more sensitive to the effect of atropine, which is not related to the contribution of autonomic tone to the heart. PMID- 1505148 TI - N-acetylcysteine enhances nitroglycerin-induced headache and cranial arterial responses. AB - The effects of N-acetylcysteine, a sulfhydryl group donor, on nitroglycerin induced headache and dilation of temporal and radial arteries were investigated in 11 healthy volunteers. Nitroglycerin, 0.06 microgram/kg/min, was infused for 20 minutes immediately after and 120 minutes after pretreatment with N acetylcysteine (100 mg/kg) or placebo. Arterial diameters were measured with high frequency ultrasound, and pain was scored by use of a previously evaluated 10 point scale. Plasma levels of free (n = 2) and total (n = 11) N-acetylcysteine were determined. N-Acetylcysteine potentiated the headache response (median headache score, 3 versus 1), and the headache retained its vascular characteristics. Temporal artery dilation was also potentiated by N acetylcysteine, 139% +/- 3% versus 127% +/- 3% of baseline, whereas the radial artery was unaffected. The potentiation was most pronounced after the first nitroglycerin infusion (12% versus 4.5% compared with placebo). A prolonged dilation of the temporal artery was observed only after the first nitroglycerin infusion, when high levels of N-acetylcysteine were present. PMID- 1505149 TI - Pharmacokinetics and pharmacodynamics of oral diazepam: effect of dose, plasma concentration, and time. AB - Eleven healthy subjects received single oral doses of placebo, 2 mg diazepam, 5 mg diazepam, and 10 mg diazepam in a randomized four-way crossover study. Plasma diazepam levels, the Digit Symbol Substitution Test (DSST), and fraction of total electroencephalographic (EEG) amplitude falling in the sigma plus beta (13 to 31 Hz) frequency range were determined during the 12 hours after drug administration. Peak plasma diazepam concentration and area under the 12-hour curve were proportional to dose; time of peak was independent of dose. Baseline percentage of EEG amplitude falling in the 13 to 31 Hz range averaged 15.7% and did not differ among the four trials. The percentage of EEG amplitude falling in the 13 to 31 Hz range did not change over baseline with placebo or 2 mg diazepam but was increased 1/4 to 2 1/2 hours after 5 mg diazepam, (maximum, +7.3%) and 3/4 to 12 hours after 10 mg diazepam (maximum, +15.2%). The increase in the percentage of EEG amplitude falling in the 13 to 31 Hz range was highly correlated with plasma diazepam concentration. DSST scores for placebo and 2 mg diazepam were nearly identical. DSST decrements with 5 and 10 mg diazepam paralleled and were correlated with the changes in the percentage of EEG amplitude falling in the 13 to 31 Hz range and with plasma diazepam levels. Thus the EEG analysis provides objective quantitation of benzodiazepine central nervous system effects, in turn reflecting plasma levels and other clinical measures. PMID- 1505150 TI - Differential plasma duration of antiplatelet-activating factor and antihistamine activities of oral Sch 37370 in humans. AB - Preclinical studies have established that Sch 37370 (1-acetyl-4-(8-chloro-5,6 dihydro-11H-benzo[5,6]-cyclohepta [1,2-b]pyridin-11-ylidene)piperidine) is an orally active antagonist of platelet-activating factor (PAF) and histamine H1 receptors with potential therapeutic use in the treatment of asthma. To evaluate the efficacy and duration of anti-PAF and antihistamine actions of oral Sch 37370 in humans, a single dose (5 mg/kg) of Sch 37370 was given orally to each of 10 male subjects in a placebo-controlled, double-blind crossover study. Blood samples were drawn before and at various times (2 to 48 hours) after Sch 37370 or placebo. Plasma samples were analyzed for Sch 37370 by a gas chromatographic method, for the anti-PAF activity by measuring the aggregation of platelets stimulated with PAF, and for the antihistamine activity by measuring displacement of [3H]pyrilamine from rat brain membrane binding sites. The plasma anti-PAF activity declined from high levels at 2 hours to barely detectable levels at 24 hours; however, significant activity was still present at 12 hours. The plasma levels of Sch 37370 closely paralleled the anti-PAF profile. The plasma antihistamine activity reached a maximum within 2 to 8 hours and declined thereafter. However, 48 hours after Sch 37370, the antihistamine activity was still present at a significant level in most subjects. It is concluded that, in humans, oral Sch 37370 antagonizes both PAF and histamine with plasma antihistamine activity lasting longer than plasma anti-PAF activity. PMID- 1505141 TI - Clinical pharmacokinetics of endocrine agents used in advanced breast cancer. AB - Endocrine therapy is important in the treatment of advanced breast cancer. The prototype antiestrogen tamoxifen and the prototype aromatase inhibitor aminoglutethimide have been in clinical use for more than 2 decades, as have synthetic progestin derivatives. Currently, several novel antiestrogens and aromatase inhibitors are used to treat breast cancer. This paper reviews the present knowledge of the clinical pharmacokinetics of these drugs. Drug monitoring in plasma and other body fluids has been improved over recent years by the introduction of sensitive and specific high performance liquid chromatography and gas chromatography-mass spectrometry methods. However, we still lack information on such basic pharmacokinetic parameters as the bioavailability of several of these drugs. It is important to study not only plasma but also tissue drug concentrations. PMID- 1505151 TI - Incidence of S-mephenytoin hydroxylation deficiency in a Korean population and the interphenotypic differences in diazepam pharmacokinetics. AB - We studied the genetically determined hydroxylation polymorphism of S-mephenytoin in a Korean population (N = 206) and the pharmacokinetics of diazepam and demethyldiazepam after an oral 8 mg dose of diazepam administered to the nine extensive metabolizers and eight poor metabolizers recruited from the population. The log10 percentage of 4-hydroxymephenytoin excreted in the urine 8 hours after administration showed a bimodal distribution with an antimode of 0.3. The frequency of occurrence of the poor metabolizers was 12.6% in the population. In the panel study of diazepam in relation to the mephenytoin phenotype, there was a significant correlation between the oral clearance of diazepam and log10 urinary excretion of 4-hydroxymephenytoin (rs = 0.777, p less than 0.01). The plasma half life of diazepam in the poor metabolizers was longer than that in the extensive metabolizers (mean +/- SEM, 91.0 +/- 5.6 and 59.7 +/- 5.4 hours, p less than 0.005), and the poor metabolizers had the lower clearance of diazepam than the extensive metabolizers (9.4 +/- 0.5 and 17.0 +/- 1.4 ml/min, p less than 0.001). In addition, the plasma half-life of demethyldiazepam showed a statistically significant (p less than 0.001) difference between the extensive metabolizers (95.9 +/- 11.3 hours) and poor metabolizers (213.1 +/- 10.7 hours), and correlated with the log10 urinary excretion of 4-hydroxymephenytoin (rs = -0.615, p less than 0.01). The findings indicate that the Korean subjects have a greater incidence of poor metabolizer phenotype of mephenytoin hydroxylation compared with that reported from white subjects and that the metabolism of diazepam and demethyldiazepam is related to the genetically determined mephenytoin hydroxylation polymorphism in Korean subjects. PMID- 1505152 TI - Increase of cytochrome P450IA2 activity by omeprazole: evidence by the 13C-[N-3 methyl]-caffeine breath test in poor and extensive metabolizers of S-mephenytoin. AB - Omeprazole has been shown to induce cytochrome P450IA1 and P450IA2 activity in vitro. To reflect cytochrome P450IA2 (CYP1A2) activity in vivo, the 13C-[N-3 methyl]-caffeine breath test was conducted in 18 volunteers: 12 extensive metabolizers, one intermediate metabolizer, and five poor metabolizers of S mephenytoin. Breath tests were performed before treatment with an oral dose of 40 mg omeprazole, on the seventh day of treatment, and after a 7-day washout period. The mean percentage exhalation of the 13C test dose, as determined by 13CO2 in breath during 8 hours, was 23.0% +/- 8.0% (n = 18) before treatment. The largest increases in exhalation rate of 13CO2 were observed in the poor metabolizers and the intermediate metabolizers (range, 12.8% to 62.9%; median, 38.9%); median area under the plasma concentration-time curves (AUC) of omeprazole was four times higher than in the extensive metabolizers. The change after omeprazole treatment in extensive metabolizers ranged from -9.8% to +47.7% (median, 12.3%; n = 12) of pretreatment values. In both groups exhalation rates of 13CO2 returned to near pretreatment values within the 7-day washout period (24.2% +/- 7.8%; n = 17). Changes in the 13C-caffeine breath test correlated well with both the pretreatment value (R = -0.67, p = 0.003; n = 18) and the plasma AUC of omeprazole (R = 0.61, p = 0.007; n = 18). Therapeutic doses of omeprazole seem to induce CYP1A2 activity in poor metabolizers, whereas they exert minor inducing effects in extensive metabolizers of S-mephenytoin. PMID- 1505154 TI - The relationship between alfentanil distribution kinetics and cardiac output. AB - The relationship between cardiac output and the tissue distribution of alfentanil was investigated in seven healthy volunteers. Subjects were given 10 micrograms/kg alfentanil and 0.5 mg/kg indocyanine green. Arterial blood samples were obtained at baseline, 1 minute, every 1/2 minute until 5 minutes, and then every minute until 15 minutes after the drug injection was begun. Subsequent samples were collected to 6 hours. Cardiac output was measured continuously by use of thoracic bioimpedance. Alfentanil pharmacokinetics were modeled with both a standard three-compartment model and a four-compartmental model based in part on the two-compartmental pharmacokinetics of indocyanine green. The sum of intercompartmental clearances for both the three- and four-compartment models were significantly correlated with the measured cardiac outputs, r = 0.93 and r = 0.88, respectively. These findings indicate that the intercompartmental clearance (i.e., tissue distribution) of alfentanil is largely determined by cardiac output (i.e., tissue blood flow). PMID- 1505153 TI - Pharmacokinetics and pharmacodynamics of ibuprofen isomers and acetaminophen in febrile children. AB - The pharmacokinetics of racemic ibuprofen and its stereoisomers have been described in adults, but little has been reported for children. The pharmacodynamics of acetaminophen and ibuprofen have not been well described in either adults or children. Children (N = 39; age range, 11 months to 11 1/2 years) were randomly selected to receive a single dose of either 6 mg/kg of liquid ibuprofen or 10 to 15 mg/kg of liquid acetaminophen (mean +/- dose given, 11.6 +/- 0.7). Pharmacokinetic and pharmacodynamic analyses were performed with temperature as the effect parameter and mean acetaminophen, total ibuprofen, and ibuprofen stereoisomer concentrations over time. Time of maximum serum concentrations for ibuprofen was 54.05 minutes versus 27.0 minutes for acetaminophen, time to maximum temperature decrease was 183 minutes for ibuprofen and 133 minutes for acetaminophen. Temperature reduction for the ibuprofen dose was significantly different than that of the acetaminophen dose at later time points (240, 300, 360, 420, and 480 minutes). Further pharmacokinetic pharmacodynamic studies with use of individual ibuprofen stereoisomers and other dosing regimens are indicated. PMID- 1505155 TI - A new method for rate of analgesic onset: two doses of intravenous morphine compared with placebo. AB - A new method of frequent early pain assessments for 1 hour only was used to determine time of onset of analgesia after intravenous administration of 10 mg morphine, 5 mg morphine, or placebo in a double-blind study; 79 patients were randomized if they required parenteral analgesia in the early postoperative period. Pain intensity was determined by a four-point categoric verbal rating scale and on a verbal ordinal scale from 0 to 100 (0 = no pain, 100 = worst pain imaginable) during the first hour after analgesic administration. The onset time of analgesia, assessed by 50% of patients achieving 25% reduction from their baseline pain assessment, was significantly faster for 10 mg morphine compared with 5 mg morphine (p = 0.02) and placebo (p less than 0.01). More familiar analgesic efficacy measures, including the sum of pain intensity differences and time to next analgesic dose, similarly showed the superiority of 10 mg morphine to placebo in the first hour, confirming sensitivity according to the conventional paradigm. PMID- 1505156 TI - The feasibility of studying drug-induced acute hepatitis with use of Medicaid data. AB - To determine the feasibility of the use of Medicaid data to study drug-induced acute liver disease, we reviewed the medical records of 414 patients receiving Medicaid, age 20 or older, with an ICD-9-CM inpatient billing code consistent with acute hepatitis. Of the patients whose records were reviewed, 15.9% were alcoholics, 31.9% had acute hepatitis A or B, 13.5% were intravenous drug users, 8.2% had acute cholecystitis or choledocholithiasis, and 4.1% had received a blood transfusion within the previous 6 months. No diagnosis of liver disease was found in 10.6% of the patients, and 5.7% had chronic liver disease. Of the 169 patients with idiopathic acute liver disease identified, many had very mild liver disease and were hospitalized for reasons other than liver disease. We conclude that Medicaid billing data has high reliability and validity for the diagnosis of acute liver disease. However, primary medical records are essential for the study of drug-induced hepatitis, to be able to exclude other causes of liver disease, and to obtain information not included in the computer data. PMID- 1505157 TI - Pharmacist with HIV. PMID- 1505158 TI - The all-payer alternative: controlling costs through competition. PMID- 1505159 TI - Wait! What is it we're trying to reform? PMID- 1505160 TI - Autonomous medical treatment decisions. PMID- 1505161 TI - Ineffective ventilation during exercise in patients with chronic congestive heart failure. AB - The pathophysiologic mechanisms causing exertional breathlessness in patients with chronic congestive heart failure (CHF) are not fully understood. Therefore, we have studied whether the ventilation in such patients is ineffective during exercise. Thirteen patients with treated chronic CHF (New York Heart Association class II-IV) and eight healthy controls underwent a maximal bicycle ergometer test with continuous analysis of expired air and frequent arterial blood sampling for gas and lactate analysis. All subjects were non-smokers and none had any signs of a pulmonary disease. Peak O2 consumption of the patients was 14.9 +/- 5.3 ml min-1 kg-1 and that of controls 33.6 +/- 7.5 ml min-1 kg-1. In patients with CHF the ratio of pulmonary dead space to tidal volume was significantly elevated at peak exercise compared with that of the controls (0.36 +/- 0.08 vs. 0.20 +/- 0.07, P less than 0.05). The ventilatory equivalent for CO2 (VE:VCO2) was also significantly higher in patients than in controls during exercise (P less than 0.05). Furthermore, both the ventilatory equivalents for CO2 and O2 (VE:VO2) had a significant inverse correlation with peak O2 consumption (P less than 0.001 for VE:VCO2 and P less than 0.05 for VE:VO2), O2 consumption at anaerobic threshold (P less than 0.01) and O2-pulse (P less than 0.001) among the patients. During exercise the arterial PO2 and PCO2 remained normal in patients and controls. These data indicate that in patients with chronic CHF wasted ventilation is pathologically increased during exercise, and this is related to the severity of the disease. Chronic CHF is not associated with decreased ventilatory reserve, hypoxaemia or alveolar hyperventilation. The ineffectiveness of ventilation is probably an important cause of exertional breathlessness in patients with CHF. PMID- 1505162 TI - Effects of sulphur hexafluoride on psychomotor performance. AB - The narcotic influence of sulphur hexafluoride on mental and psychomotor performance has been studied in 9 subjects at normal atmospheric pressure. Control experiments were performed with air and with nitrous oxide. Psychomotor, perceptual and cognitive abilities were assessed using a computerized test battery. Subjects were exposed to air and six different normoxic gas mixtures: 13, 26, and 39% N2O, and 39, 59, and 79% SF6. Significant performance impairments were found with 13% N2O and gradual further impairment with 26, and 39% N2O. During exposure to 39, 59, and 79% SF6 over-all performance was impaired by 5, 10, and 18%, respectively. Impairment was significant with 59 and 79% SF6. The results indicate that the relative narcotic potency of SF6: N2O is about 1:4 in humans. It is concluded that a normoxic SF6-O2 mixture can be inhaled for lung function studies without any harmful effects and that the short-lasting narcotic effect, although detectable with a test battery, would not impair the ability of the subject to perform simple breathing procedures. PMID- 1505163 TI - The creatine kinase system in the serum of runners following a doubling of training mileage. AB - This study examined the response of the serum creatine kinase (CK) isoenzyme/isoform system following the stress of successive weeks of increased training. Four highly-trained male long-distance runners doubled their training mileage [45.0 (SD 3.5) to 81.2 (4.7) miles] for 3 weeks. Venous blood samples were obtained prior to the start of the increased training period and at the end of each week, days 7, 14, and 21, 12 h after a training run. All runners experienced a significant increase in training perception difficulty, which correlated with the significant increase in training mileage. While total CK activities did not become significantly elevated until day 14, the tissue isoform CK-MM3, as well as the ratio of CK-MM3 to MM1 (final CK-MM degradation isoform) became significantly elevated at day 7 and remained elevated throughout day 21. These findings demonstrate that an increase in training mileage caused a significant and continuous release of tissue CK activity from skeletal muscle into the circulation. PMID- 1505164 TI - Redistribution of skin blood flow during leg dependency in peripheral arterial occlusive disease. AB - A disturbed autoregulation of cutaneous blood flow in legs with peripheral arterial occlusive disease (PAOD) has previously been demonstrated for circumscribed skin areas. In the present study, posturally-induced changes of skin perfusion distribution along ischaemic limbs were investigated topographically in 35 PAOD patients by means of fluorescein perfusography. Among the 68 legs studied, 7 had patent arteries and 61 could be assigned to FONTAINE stages I to IV. Limbs with peripheral skin lesions (stage IV) were further differentiated according to either healing (stage IV+) or non-healing (stage IV-) on conservative treatment. Sitting-up always led to prolonged calf as well as foot fluorescein appearance times (AT) except for legs in stage III or IV- disease. In the latter two groups, decreased sitting as compared to supine AT foot-to-calf ratios indicated a relative shift of dye delivery from proximal towards distal skin regions during posture. In contrast, this measure of blood flow redistribution did not change in the other groups. The redirection of fluorescein influx was significantly correlated with the systolic arterial pressure ankle-to-arm ratios. In conclusion, besides small perfusion pressure increases or passive microvessel distension, a shift of the peripheral resistance ratios may contribute to the improved blood supply of ischaemic skin regions during leg dependency. An arteriolar vasoparalysis does not regularly exist in limbs with skin lesions not primarily originating from ischaemia (stage IV+). PMID- 1505165 TI - Sham-feeding decreases cardiac output in normal subjects. AB - The cardiovascular effect of sham-feeding was measured in seven healthy non-obese human subjects by the Fick principle using the carbon dioxide rebreathing method. The subjects were resting in the sitting position and were exposed to the sight and smell but not the taste of a breakfast meal. Cardiac output decreased significantly from a mean value of 4.0 1 min-1 to 3.5 1 min-1 during sham-feeding (Friedman, P = 0.004). The cardiac output returned to basal values in all seven subjects when the sensory stimulus was removed. The decrease in cardiac output was due to a decreased stroke volume, whereas heart rate and blood pressure did not change. The mechanism of the decrease in cardiac output during sham-feeding remains to be established. PMID- 1505166 TI - Longitudinal systolic shortening of the left ventricle: an echocardiographic study in subjects with and without preserved global function. AB - The atrioventricular (AV) plane displacement was studied by echocardiography in 79 subjects (45 healthy subjects and 34 patients with acute myocardial infarction or chronic congestive heart failure). From apical 4- and 2-chamber views the displacement of the AV plane towards the apex in systole was recorded at 4 sites in the left ventricle (LV) corresponding to the septal, anterior, lateral, and posterior walls and the mean value from the above 4 sites (AV-mean) was calculated. In addition, in healthy subjects, the AV plane displacement at right ventricular free wall was also recorded. The AV-mean correlated well with the echocardiographic ejection fraction determined by biplane area-length method (r = 0.96, P less than 0.001). The correlation was also high when the percentage of the left ventricular shortening along the long axis was used (r = 0.97, P less than 0.001). The correlation between ejection fraction and AV-mean was also good when separate analysis was made for the subjects with preserved ejection fraction (r = 0.86, P less than 0.001) and decreased ejection fraction (r = 0.82, P less than 0.001). The right ventricle had a significantly higher AV plane displacement (P less than 0.001) than the LV. The study also includes determination of the muscular excursions of the septal and posterior walls along the short axis of the left ventricle from the parasternal long axis view. The AV plane displacement of the respective walls was relatively greater (P less than 0.001) compared to concentric contractions. The septal and posterior wall excursions along the short axis correlated poorly with the AV plane displacement of the respective walls (r = 0.55, P less than 0.01 and r = 42, P less than 0.05). PMID- 1505167 TI - Subtraction of extra-renal background in 99mTc-DTPA renography: comparison of various regions of interest. AB - Quantitative evaluation of renal function in 99mTc-DTPA isotope renography is hampered by high background activity. This study compares various background regions of interest (ROIs) to obtain the most accurate estimate of the extra renal background, taking both total counts (integral value) and change by time (slope) into account. Gamma camera renography was performed in 21 patients with a single kidney. Time-activity histograms obtained from 8 different background ROIs were compared in the time interval corresponding to the uptake phase of the renogram with the histogram obtained from a ROI over the empty kidney area. A significant difference could be demonstrated between the slope values of the histograms of the right and left empty kidney ROIs, but not for the integral values. Backgrounds taken over the heart, liver, between the kidneys, and under the kidneys had significantly different characteristics than the one in the empty kidney area. Only background ROIs surrounding each kidney area gave integral and slope values with close resemblance to those recorded over the empty kidney area. The results emphasize the necessity for an individual background ROI for each kidney and the need to separate extra- and intra-renal background activities before subtraction. PMID- 1505168 TI - Testing arterial baroreflex function in acutely unwell patients. AB - Cardiovascular function is deranged in acute illnesses but specific details of this pathophysiological phenomenon are poorly understood. With advances in intensive care it is now necessary to define these changes. Existing tests of cardiovascular reflex function are ill-suited to the study of acutely unwell patients. The arterial baroreflex is the principal cardiovascular homeostatic reflex. We have modified the neck suction test of baroreflex function such that it can be performed in 30 min using portable equipment. The protocol was validated on control subjects. Testing of injured patients showed that this test and protocol could be used sequentially, beginning within 2 h of injury, to demonstrate acute changes in baroreflex function and to follow these changes through the disease process. Patient tolerance of the test was excellent. Subsequently, further modification developed an even shorter protocol whereby similar information could be obtained within 15 min. The cardiac response to deep respiration can be measured with minimal patient upset or compliance and is ideal for repetitive testing in critically ill patients. This is not a specific test of baroreflex function but responses to it show interesting parallels with changes in baroreflex function which merit further study. PMID- 1505169 TI - Does diffuse coronary atherosclerosis affect the relation between coronary stenoses and uptake of thallium-201 after exercise? AB - It has been proposed that diffuse coronary atherosclerosis influences the myocardial perfusion. We performed a study of 94 young men with previous myocardial infarction in order to find out whether the presence and extent of diffuse coronary atherosclerosis affected the relation between maximal stenosis and myocardial perfusion in areas remote from the infarction. The patients were examined by planar-imaging thallium-201 scintigraphy, following exercise, and coronary angiography within 6 months after myocardial infarction. The maximal distinct stenosis and diffuse coronary atherosclerosis, comprising both plaque size and extent, were semiquantitatively assessed. The correlation coefficients between maximal stenosis within the LAD, RCA, and LCX vascular territories and the corresponding initial uptake of thallium were 0.52 (P = 0.0001), 0.30 (P = 0.04), and 0.46 (P = 0.02), respectively. No change of the correlations was found, except for a slight increase of the r-value from 0.30 to 0.37 in regions corresponding to RCA, after controlling for the diffuse atherosclerosis score in a multiple stepwise regression analysis. These findings indicate no impact of diffuse coronary atherosclerosis on regional myocardial perfusion in areas remote from the infarction. PMID- 1505170 TI - Is the high lactate release during arm exercise due to a low training status? AB - To determine whether arm lactate release during arm exercise is related to the training status of the arms, seven arm-trained athletes were studied during 30 min of continuous arm exercise (AE) or leg exercise (LE) of increasing intensities corresponding to 30%, 50%, and 80% of peak VO2 during AE and LE respectively. Blood vessels were catheterized for determination of regional blood flows and substrate exchanges. The respiratory exchange ratio was higher during AE than LE (P less than 0.01). The arteriovenous oxygen difference, [(A-V)O2], for the leg during LE was 11-19% higher than the (A-V)O2 for the arm during AE (P less than 0.01). At the highest intensity the (A-V)O2 was 170 +/- 6 ml O2l-1 during LE, vs. 143 +/- 9 during AE (P less than 0.01). Arm blood flow in relation to limb volume was 56-95% higher during AE (P less than 0.05). Arterial lactate concentrations were 27-60% higher during AE (P less than 0.01) and lactate release from the exercising limb was 2-4 times higher (P less than 0.05) during AE compared to LE. Adrenaline and noradrenaline rose 6- and 21-fold, respectively, during AE and did not differ from corresponding LE values. During AE the (A-V)O2 difference across the arm, arterial lactate concentration, and arm lactate release were of the same magnitude in arm-trained and relatively less arm trained subjects. Lactate release in relation to O2 uptake by the exercising limb was 7-37% lower during AE in arm-trained subjects compared to AE in arm-untrained subjects but was 3-6 times higher than the corresponding relation during LE (P less than 0.01). We conclude that AE is associated with a larger lactate release compared to LE. This difference is only to a minor extent influenced by intense training of the arms. The high arm vs. leg lactate release appears to be associated with differences in regional circulatory adaptation by the exercising limb. PMID- 1505171 TI - Non-invasive assessment of vessel-wall changes in hypertensives and normotensive controls. AB - The aim of this study was to evaluate the feasibility of non-invasive assessment of vessel wall changes in early, untreated hypertension. Measurement of intimal+medial (I-M) thickness in the common carotid artery (CCA) using B-mode ultrasound imaging showed no differences between 12 patients with untreated, newly diagnosed hypertension and 9 age-matched controls (0.63 mm vs 0.63 mm just proximal to the carotid bulb). Echocardiography showed that the hypertensive group had thicker left ventricular walls (LVW) than the normotensive group. Correlation analyses disclosed that I-M thickness was significantly associated with age (r = 0.63; P less than 0.05) for the whole material but not with blood pressure levels, serum lipids, or LVW thickness. These results imply that the arterial I-M layers of the CCA are less responsive to pressure overload than the left ventricle. The feasibility of using I-M thickness as an early marker of structural vessel wall changes in hypertensive patients must await results from large scale prospective studies. In view of the present results, age homogenous materials should be selected for such studies. PMID- 1505172 TI - [Ketoprofen efficacy and tolerance in simple painful shoulder]. AB - Thirty patients presenting with painful shoulder syndrome were treated with i.m. ketoprofen 100 mg b.d. for 8 days to assess the efficacy and tolerance of the above treatment regime. The patients' condition was monitored by clinical, instrumental and laboratory examinations. Ketoprofen was found to be significantly effective in all cases of non calcific rotator cuff tendinitis while no improvement was noted in calcific tendinitis. The above data confirm the efficacy and tolerance of ketoprofen in the treatment of painful shoulder syndrome as an alternative to local steroid therapy. PMID- 1505173 TI - [Potassium canrenoate and the combination of potassium canrenoate-butizide in the therapy of light to moderate arterial hypertension]. AB - The aim of the study was to evaluate the antihypertensive effect of K-canrenoate, alone or in combination with butizide, in mild to moderate essential hypertensives. Fifteen patients (supine diastolic blood pressure ranging from 95 to 114 mmHg) received K-canrenoate 50mg/die (step 1). In patients with supine diastolic blood pressure greater than 90 mmHg therapeutic regimen was modified at two-week intervals according to the following design: K-canrenoate 100 mg/die (step 2), K-canrenoate 50 mg + butizide 5 mg/die (step 3), K-canrenoate 100 mg + butizide 10 mg/die (step 4). Blood pressure control was achieved in 2 patients treated with K-canrenoate alone (step 2) and in 8 patients on a combined regimen (step 3), and it was maintained throughout the whole trial period (12 weeks); step 4 did not achieve the goal of therapy in the remaining 5 subjects. A statistically significant increase in triglyceridemia (123.2 +/- 42.1 vs 158.3 +/ 62 mg/dl) and uricemia (4.6 +/- 0.9 vs 5 +/- 0.9 mg/dl) was observed at the end of the follow-up period. Serum potassium levels remained stable in all patients. Therefore, K-canrenoate in combination with butizide is an effective and well tolerated drug in the treatment of mild to moderate essential hypertension. PMID- 1505174 TI - [The tasks and aims of prevention]. AB - The purpose of the above note was to offer an overall view of preventive medicine the fundamental object of which is the safeguard of the state of health before the manifestation of disease. Prevention is therefore closely related to epidemiology which looks for causes and identifies risk factors. These tasks must be performed with constant effort and tenacity on the one hand by the state via the necessary public health organizations (personnel, facilities, programming), and on the other by the community as well as by the individual citizen who, being the user and driving force, must take advantage of the benefits and at the same time work for better results through changes in his own behavior and lifestyle. PMID- 1505175 TI - [Meteoropathy: a syndrome continuously on the increase]. AB - The authors describe the different kinds of meteoropathies, pointing out how these disorders are becoming ever more frequent in countries belonging to the consumer and welfare society due to the progressive lowering of body resistance and immunologic responses. These "unfavourable meteosyndromes", as meteoropathies should be called, develop when wave disturbances arrive, and are more manifest and persistent in subjects with neurologic disturbances, i.e. in the presence of anxiety, stress, hypertension, coronary artery disease, arthropathy, hyperthyroidism, etc. The different moments in which meteoropathies are more frequent and the possible therapies are also discussed. PMID- 1505176 TI - [The clinical evaluation of the hypocholesterolemic effects of an inhibitor of cholesterol synthesis: mevalonic acid]. AB - Twenty eight patients with heterozygous familial hypercholesterolemia were treated with mevalonic acid (an inhibitor of cholesterol synthesis) for 45 days. Patients received a daily dose of 750 to 1500 mg mevalonic acid depending on plasma cholesterol levels. Results showed a significant reduction in cholesterol values whereas no significant difference was observed in HDL cholesterol and triglyceride levels. PMID- 1505177 TI - [Yersiniosis]. AB - The authors' objective in the above review was to stress the epidemiological importance of Yersinia enterocolitica infections. They therefore detail the clinical and epidemiologic features of acute or primary as well as of secondary forms and complications of Yersinia enterocolitica infections. Further, they dwell on the management of these infections and illustrate the properties, toxic effects and other side effects of the antibiotics commonly used in therapy and for the prevention of complications. Finally, they take stock of the regulations to be applied for the prevention of this complex and multifaceted infection. PMID- 1505178 TI - Role of keratinocytes in allergic contact dermatitis. AB - Although once thought to play a purely structural role, there is increasing evidence that keratinocytes are actively involved in epidermal immune responses, including allergic contact dermatitis (ACD). In vitro studies demonstrate that both urushiol and nickel sulphate induce cytokine production in cultured keratinocytes including molecules responsible for endothelial cell activation and lymphocyte chemotaxis and adhesion. In vivo, these same molecules are expressed in experimentally induced patch test reactions to a variety of allergens. Furthermore, such expression precedes the onset of the inflammatory phase of ACD. Taken together, these studies suggest a role complementary to that of Langerhans cells for keratinocytes in the initiation and propagation of ACD. PMID- 1505179 TI - A comparative study of formaldehyde detection using chromotropic acid, acetylacetone and HPLC in cosmetics and household cleaning products. AB - Chromotropic acid and acetylacetone methods for qualitative determination of formaldehyde were tested in parallel on 48 commercial samples, with high performance liquid chromotography (HPLC) implemented for quantitative measure. In addition, interference with the detection of formaldehyde was investigated by analyzing 12 other aldehydes and ketones, 7 essential oils and 3 polysorbates. Throughout this comparative study, the disadvantages of the chromotropic acid method, of which 2 variants were used, were delineated and we found that the acetylacetone test proved to be a more efficient screening method for formaldehyde detection in a clinical laboratory. PMID- 1505180 TI - Corticosteroid or steroid allergy? AB - The aim of this study was to elucidate the role of the C11-OH substituent of the corticosteroid molecule in relation to contact allergy to corticosteroids. This group, which is essential for glucocorticoid activity, is not present in other steroid molecules, such as deoxycortisol, progestagens, testosterone, and estrogen. Skin tests with these substances in hydrocortisone-allergic patients revealed a division between patients for whom the C11-OH group was essential to induce the allergic reaction and patients for whom this group did not seem to be essential. Some of the patients of the latter group also reacted to 17-alpha-OH progesterone. This may indicate cross-sensitivity between hydrocortisone and 17 alpha-OH-progesterone, which might play an etiological role in autoimmune progesterone dermatitis. PMID- 1505181 TI - Permeation and destructive effects of disinfectants on protective gloves. AB - In working situations where there is a possibility of acquiring blood-borne infections, the use of disinfectants is important. It is also important to use protective gloves, both to protect the skin against disinfectants and to protect against infections. Changes in the structure of the glove material may, however, interfere with the protective capability of the gloves. The influence of 4 disinfectants on the material structure and protective effect of 6 different brands of protective gloves was studied. The proposed International Organization for Standardization (ISO) standard method for determining the liquid chemical resistance of air-impermeable materials was used for permeation testing. Pieces of latex and vinyl glove were also exposed to isopropanol and ethanol for 10, 30 and 60 min and then viewed in a scanning electron microscope. Isopropanol permeated through latex and vinyl gloves in less than 10 min. The polyethylene (PE) gloves were of quite variable quality, and the breakthrough time ranged from 4 to greater than 240 min. The latex and vinyl gloves were also permeated by ethanol, but at a much lower rate. The disinfectants Blifacid, based on p-chloro m-cresol, and Cidex, based on glutaraldehyde, did not permeate any of the gloves tested within 60 min. Isopropanol had a destructive effect on the material, which became opaque, stiff and brittle. This change in structure was verified with the scanning electron microscope. The tested gloves of latex, vinyl and PE, gave acceptable protection from contact with Blifacid and Cidex for at least 60 min. The same gloves do not give any total protection from contact with isopropanol and ethanol. PMID- 1505182 TI - Cutaneous reactivity to allergens at 24-h increases from the antecubital fossa to the wrist: an echographic evaluation by means of a new image analysis system. AB - To establish the existence of regional variations in response to allergens, we performed patch tests with nickel sulfate 5% pet. at 4 different sites on the volar forearm skin in 17 nickel-sensitive women, aged from 18 to 45 years. After a 24-h application, patch tests were removed and evaluated both by clinical scoring and by means of a 20 MHz ultrasound B scanner. Recorded echographic images referring to uninvolved skin and to positive test sites were evaluated by a traditional image analysis method for the determination of skin thickness. Furthermore, they were processed by software which ascribes arbitrary values to the amplitude levels of the echoes and enables quantification of the pixels, (the smallest elements in a visual display with controllable colour and brightness) forming objects reflecting within a selected amplitude band. Thus, we demonstrated an increase in thickness of uninvolved skin at distal sites and a greater reactivity at 24 h to patch tests in skin areas near to the wrist crease, as evidenced by a greater increase in pixel and in thickness values at distal sites. From our data, we have a clear indication for the use of rotating patterns or symmetrical sites in quantitative and comparative investigations concerning the evaluation of contact allergy on volar forearm skin. PMID- 1505183 TI - Contact and photocontact allergy to oxybenzone. AB - The purpose of this study was to determine the frequency of contact allergy and photocontact allergy to sunscreens. A consecutive series of 54 patients with suspected clinical photosensitivity were assessed. All had the same standardized photobiological investigation from January 1989 to December 1990, including patch tests and photopatch tests with 6 sunscreen agents. Oxybenzone was found to cause 4 cases of allergic contact dermatitis (with photoaggravation in 2), and 3 cases of photocontact dermatitis (13% of patients). This is probably due to the wide distribution of oxybenzone in sunscreens and other cosmetics, 2 patients with polymorphic light eruption and persistent light reactivity, respectively, were regular sunscreen users. Photobiological investigation is necessary to ensure accurate diagnosis, since sunscreen contact or photocontact allergy may simulate other photosensitivity eruptions. PMID- 1505184 TI - Results of routine patch testing with corticosteroid series in 2073 patients. AB - The patch test results of 61 patients allergic to at least 1 corticosteroid molecule are presented. These contact allergies were detected by testing with several corticosteroids included in our standard patch test series between February 1988 and December 1990. Whenever possible, further investigations were conducted by means of a more complete corticosteroid series. We found corticosteroids to be the 7th most frequent allergen, positive results being obtained in 2.9% of all patients referred to our contact dermatitis unit. In this series, budesonide was the most common allergen and often gave simultaneous reactions with other corticosteroids. PMID- 1505185 TI - Are barrier creams of any use in contact dermatitis? PMID- 1505186 TI - Contact urticaria induced by Semecarpus anacardium. PMID- 1505187 TI - How large a proportion of contact sensitivities are diagnosed with the European standard series? PMID- 1505188 TI - Regional variations of patch test response in nickel-sensitive patients. PMID- 1505189 TI - Occupational allergic contact dermatitis from ethyl-2-bromo-p methoxyphenylacetate. PMID- 1505190 TI - Patch testing with corticosteroids in xerogel formulations. PMID- 1505191 TI - Grapeseed oil as a safe and efficient hand cleansing agent. PMID- 1505192 TI - Allergic contact stomatitis from methyl methacrylate in a dental prosthesis, with a persistent patch test reaction. PMID- 1505193 TI - Echographic evaluation of corticosteroid inhibition of allergic patch test reactions. PMID- 1505194 TI - Demonstration of epidermal and dermal cell-bound IgE in differentiating between atopic and contact dermatitis. PMID- 1505195 TI - In vitro stimulation of retinal pigment epithelium proliferation by taurine. AB - Taurine is an amino acid that is essential for retinal integrity and function. Although it has been suggested that the ratio of melatonin to taurine in the interphotoreceptor matrix may regulate the phagocytosis of outer segments by retinal pigment epithelial (RPE) cells, the effect of taurine on the RPE has not been studied. Using cultured RPE cells, we found that in vitro taurine specifically stimulated proliferation of human and rabbit RPE, but had only minimal effect on cultured scleral fibroblasts. The RPE proliferation was due to more cells entering into S-phase and thus an increase in DNA synthesis, was not dependent upon cell density, and was most pronounced in the presence of a low concentration of fetal bovine serum. PMID- 1505196 TI - Morphology and movement of corneal surface cells in humans. AB - We examined the morphology of the corneal surface epithelial cells in 13 eyes of 13 subjects using specular microscopy. We determined cell area, perimeter, and shape comparing the central cornea with the inferior and superior periphery. We found surface epithelial cells are significantly smaller in the central cornea. The cells measured 560 +/- 93 square microns in the central cornea, 850 +/- 135 square microns in the superior cornea and 777 +/- 176 square microns in the inferior cornea (p less than .005). Newly emerged surface cells are smaller and are thought to enlarge with time. We postulate that lid shearing forces are greater in the central cornea and contribute to epithelial cell exfoliation. We further postulate that preferential shearing of central corneal surface cells is an important factor driving the centripetal movement of corneal epithelial cells. PMID- 1505197 TI - A comparison of intraocular pressure elevating activity of loteprednol etabonate and dexamethasone in rabbits. AB - A "Soft" corticosteroid, loteprednol etabonate I, designed based on the "inactive metabolite" concept can be used as a safe ophthalmic anti-inflammatory drug. By design, the metabolism of I follows a predicted biotransformation pathway, thus unwanted systemic side effects are avoided. Local side effects are also reduced. Accordingly, in a cross-over study I did not elevate the intraocular pressure (IOP) in rabbits, as opposed to dexamethasone. PMID- 1505198 TI - Microendoscopic observations of the hemodynamics in the rabbit ciliary processes. AB - The in vivo hemodynamics of the ciliary process vasculature in the albino rabbit were studied with an improved technique of intraocular microendoscopy. The spreading pattern and velocity of the dye front has been observed in defined vessel segments following intracarotid injection of Evans Blue. In the anterior portion of the ciliary processes a "thoroughfare channel" (bypass) was found leading from the arteriolar tree directly into the marginal venule bypassing the capillary network of the ciliary processes. This bypass is characterized by a higher blood flow velocity (1.5-3mm/sec) than was found for the capillary network (0.8-1mm/sec). A stoppage of blood flow was observed in the capillary network at 45-50mmHg after step-wise elevation of intraocular pressure (IOP): blood flow was not stopped in the thoroughfare channel until IOP values of 55-60mmHg were reached. Intraarterial administration of vasoconstrictive agents could lead to a complete stoppage of blood flow in the capillary net whereas the marginal route often remained patent. PMID- 1505199 TI - Stimulation of phospholipase D by phorbol esters and ionomycin in bovine corneal epithelial cells. AB - This study was performed to determine the effects of phorbol esters and ionomycin on phospholipase D (PLD) activity in bovine corneal epithelial cells (BCEC). The cells were prelabeled with [3H]myristic acid and incubated for specific time intervals with various test agents in the presence and absence of ethanol. The PLD activity was assayed by monitoring the formation of labeled phosphatidylethanol ([3H]PEt) in [3H]myristate labeled cells. In the absence of ethanol, 1 microM phorbol 12-myristate 13-acetate (PMA) increased the formation of labeled phosphatidic acid ([3H]PA) with no significant effect on the radioactivity of [3H]PEt. In the presence of 85 mM ethanol, whereas there was only a small further increase in [3H]PA, the formation of [3H]PEt was increased by several-fold, demonstrating activation of PLD by the phorbol ester. The effects of PMA were time- and dose-dependent, and were mimicked by phorbol 12,13 dibutyrate. The inactive phorbol derivatives, 4-alpha-phorbol, 4-alpha-phorbol 12,13-didecanoate, 4-alpha-phorbol 12-myristate 13-acetate and 4-alpha-phorbol 12,13-dibutyrate, were without effect. Short-time (30 min) incubation of BCEC with staurosporine or H-7, or prolonged (20 hours) incubation with PMA rendered the cells less sensitive to subsequent treatment with PMA, suggesting that activation of PLD in the cells is mediated by protein kinase C (PKC). Addition of 20 microM ionomycin in the presence of ethanol also increased the formation of [3H]PA and [3H]PEt in a time- and dose-dependent manner. Co-presence of ionomycin and PMA at submaximal concentrations in the incubation medium resulted in increased formation of [3H]PA and [3H]PEt which was less than their individual effects combined, indicating a lack of synergism between Ca2+ and PMA in activating PLD. Incubation of BCEC with staurosporine resulted in significant inhibition of ionomycin-induced production of [3H]PEt, suggesting that in addition to direct activation of PLD by Ca2+, the enzyme is probably stimulated by sequential activation of PLC (producing diacylglycerol) and PKC following the ionomycin addition. We conclude that BCEC possess PLD which is stimulated by PKC as well as elevated intracellular Ca2+. PMID- 1505200 TI - The effects of 5-fluorouracil and mitomycin C on the corneal endothelium. AB - 5-Fluorouracil (5-FU) and Mitomycin C (MMC) are used as adjunct chemotherapy during glaucoma filtering surgery to suppress conjunctival fibroblast proliferation. Since part of these agents may gain access to the anterior chamber and cause cytotoxicity to the corneal endothelium we set up an in vitro system to establish a dose-response effect. Cytotoxicity of MMC and 5-FU was quantified using Mosmann's colorimetric assay in a bovine endothelial cell culture system. In this assay the respiratory activity of the cells is used as a marker for cell viability. After incubation for 5 minutes the 3.0 mg/ml concentration of MMC showed endothelial cytotoxicity, whereas no endothelial toxicity of 5-FU was noted in concentrations up to 50 mg/ml. After incubation for 30 minutes endothelial cytotoxicity was demonstrated for 50 mg/ml of 5-FU and 1 mg/ml of MMC. After an exposure-time of 60 minutes the toxicity level remained 50 mg/ml for 5-FU but decreased to 0.5 mg/ml for MMC. We conclude that with respect to the clinically used concentrations and methods of application of 5-FU and MMC in vivo endothelial toxicity is not to be expected. However, in cases of accidental access of MMC to the anterior eye chamber and following a reduction of aqueous turnover rate the safety of MMC is unwarranted. PMID- 1505201 TI - Cytokines and uveitis, a review. AB - Although the exact pathogenic mechanisms underlying uveitis are unknown, cytokines appear to be involved in this inflammatory disorder. This review describes the studies in which the uveitogenic properties of several cytokines, including tumor necrosis factor (TNF), interleukin 1 (IL-1), IL-6, IL-8 and interferon gamma (IFN-gamma), were investigated and the reports on intraocular expression of cytokines, such as TNF, IL-2, IL-6 and IFN-gamma, during uveitis. The exact contribution of these mediators to uveitis remains to be determined. This may provide new clues in the treatment of uveitis. PMID- 1505202 TI - Pediatrics and child advocacy: preparing for the 21st century. PMID- 1505203 TI - Weaning: historical perspectives, practical recommendations, and current controversies. PMID- 1505204 TI - Molecular and cellular biology of Shigella flexneri invasiveness: from cell assay systems to shigellosis. PMID- 1505205 TI - The large virulence plasmid of Shigella. PMID- 1505206 TI - Functional morphology of the crop of Drosophila auraria. AB - The crop epithelium of Drosophila auraria consists of a single layer of thin epithelial cells whose apex is covered with cuticle. The epithelial cells contain small amounts of rough endoplasmic reticulum, Golgi complexes and secretory granules. The digestive activities of the crop cavity are probably due to enzymes provided by the salivary glands and midgut cells. The epithelium displays continuous folds, which are more frequent in the upper region. The crop of Drosophila is capable of expanding and shrinking, as indicated by starvation and refeeding experiments. Starvation resulted in extensive epithelial folds and a concomitant decrease in the crop volume, while the refed insects displayed an unfolded crop epithelium and a voluminous crop. PMID- 1505207 TI - Ultrastructure of the hyphae and conidia of Arthrinium aureum. AB - Electron microscopic observations of structures in Arthrinium aureum, which have not previously been described, are presented and discussed. Considerable attention is given to cytoplasmic inclusions, especially nuclei, mitochondria and Woronin bodies. PMID- 1505208 TI - The mosquitocidal activity of conidia of Tolypocladium tundrense and Tolypocladium terricola. AB - Tolypocladium tundrense and T. terricola UV-irradiated conidia exhibited acute toxicity to Aedes aegypti larvae in concentrations of 5 x 10(5) and 5 x 10(6) ml 1, respectively. Substances deposited on the surface of conidia following sporulation appear to be responsible for rapid intoxication and killing of mosquito larvae. Treatment of larvae with dried methanolic extract of the spores also induced a high level of mortality accompanied by the same histological changes, including vacuolization and subsequent destruction of mitochondria of the midgut cells. Cyclosporin A was identified as a predominant metabolite forming the spore surface layer. PMID- 1505209 TI - Puffing activity of the salivary gland chromosomes of Drosophila bicornuta. AB - The puffing activity of the salivary gland chromosomes during late third instar and white prepupal development, as well as after in vitro culture with or without ecdysterone of Drosophila bicornuta, was investigated. D. bicornuta belongs to the montium subgroup of the melanogaster species group, and these results are discussed and compared with those of other species of the montium subgroup. PMID- 1505210 TI - Ultrastructural changes in Culex pipiens larvae treated with tolypin, the insecticidal metabolite of Tolypocladium inflatum gams (Deuteromycetes). AB - Tolypin, the insecticidal metabolite of the entomopathogenic fungus of the genus Tolypocladium, causes knock-down effect followed by high mortality in treated Culex pipiens molestus larvae. Histopathological changes accompanying the knock down symptoms were similar in all tissues. Mitochondria, the main target in the cells, were destroyed and consecutively changed into vacuoles with the remains of cristae and lysed internal structures. Despite destruction of the internal content of individual organelles, the membranes of the cell surfaces, the endoplasmic reticulum, the nuclei, and the covering membranes of tissues and organs, were not affected and remained intact until final autolysis of the tissues. Some mitochondria in intoxicated cells were destroyed completely, but others remained intact and apparently structurally unchanged. PMID- 1505211 TI - A chromosomal survey of four species of gekkonid lizards. AB - The karyotypes of the gekkonids were serially graded from the largest to the smallest in the diploid complement. The majority of the chromosomes were subtelocentric. The diploid number was 2n = 38 in Gekko gecko and 2n = 40 in the three species of the genus Hemidactylus examined. A comparative morphometric analysis of the diploid sets of these four members suggested a cytotaxonomic relationship and a possible mode of speciation in this group of reptiles. PMID- 1505212 TI - An hypothesis for a contractile protein based on the principles of submicroscopic physiology. AB - The discovery of the polyguanidinium ring complex and its various properties has emphasised the versatility of arginines in functional proteins. In an extension of these studies the possibility of formulating a polypeptide which could be the basis for a contractile element in muscle presented itself. Although hypothetical, the deduced molecular properties, based on the unique chemistry of arginine guanido groups are in keeping with known functional aspects of some muscles, and could form the foundation for a more detailed theory of muscular contraction. The structural requirements and the theoretical principles involved are briefly described in this paper. PMID- 1505213 TI - Detection of small, single-copy genes on protein-G-banded chromosomes by electron microscopy. AB - A method for the detection by electron microscopy of chromosome banding after in situ hybridization of small, nonradioactive DNA sequences is described. Typical high-resolution G-banding is produced by adding 5-bromodeoxyuridine (BrdU) during the last part of the S-phase and by applying a monoclonal antibody against the BrdU-substituted chromosome segments, followed by the addition of protein G, but no further treatment. A protocol for in situ hybridization of small, single-copy biotinylated DNA sequences and their detection by immunogold tagging on banded chromosomes is also described. This combined approach permits high-resolution mapping of small DNA sequences and should be useful in discriminating between neighboring DNA fragments. PMID- 1505214 TI - Regional mapping of a liver alpha-subunit gene of phosphorylase kinase (PHKA) to the distal region of human chromosome Xp. AB - X-linked liver glycogenosis (XLG) is a glycogen storage disorder resulting from deficient activity of phosphorylase kinase (PHK). PHK consists of four different subunits: alpha, beta, gamma, and delta. Several genes encoding PHK subunits have been cloned and localized, but only the muscle alpha-subunit (PHKA) gene has been assigned to the X chromosome, in the region Xq12----q13. However, we have previously excluded the muscle PHKA gene as a candidate gene for the XLG mutation, as linkage analysis indicated that the mutation responsible for XLG is located in Xp22 and not in Xq12----q13. We report here the chromosomal localization by in situ hybridization of a liver PHKA gene to the distal region of chromosome Xp. Strong hybridization signals were observed on the distal part of the short arm of a chromosome identified as the X chromosome by cohybridization with an X chromosome-specific centromeric probe. The localization of this gene in the same chromosomal region as the disease gene responsible for XLG suggests that the liver PHKA gene is a highly likely candidate gene for the XLG mutation. PMID- 1505215 TI - Sublocalization of an invasion-inducing locus and other genes on human chromosome 7. AB - By somatic cell fusion studies between noninvasive mouse T-lymphoma cells and invasive human activated normal T-cells we have previously shown that the genetic information responsible for the induction of invasive and metastatic potential in interspecies T-cell hybrids is located on human chromosome 7. Apparently, genes derived from normal activated T-cells are dominantly expressed in the hybrids and control the invasive and, as a consequence, metastatic potential of these T lymphoma cells. To sublocalize the invasion-inducing locus on chromosome 7 we have generated hybrids that harbor only specific regions of human chromosome 7 with or without a small fragment of human chromosome 21. Analysis of these hybrids revealed that the invasion-inducing locus maps to 7p12----cen. The human DNA complement of the hybrids was confirmed by Southern blot analysis using a large panel of chromosome 7-specific DNA probes. Several of these genes could be further sublocalized. These included: ARAF2 to 7p12----cen, D7S21 to 7pter--- p12, ACTB to 7p15----p12, EGFR to 7p12, MDH2 to 7cen----q22, and PDGFA to 7pter-- -p15. PMID- 1505216 TI - The human platelet-derived growth factor alpha chain (PDGFA) gene maps to chromosome 7p22. AB - The human PDGFA gene has been mapped previously to two different sites on chromosome 7 (7p21----p22 and 7q11.2----q21.1). Using in situ hybridization and human x mouse somatic cell hybrid lines we present data which confirm the localization of PDGFA to the terminal short arm of chromosome 7, at 7p22. PMID- 1505217 TI - Assignment of the aspartylglucosaminidase gene (AGA) to 4q33----q35 based on decreased activity in a girl with a 46,XX,del(4)(q33) karyotype. AB - Aspartylglucosaminuria (AGU) is a recessive autosomally inherited lysosomal storage disorder due to deficiency of the enzyme aspartylglucosaminidase (AGA). The structural gene for this human enzyme (AGA) has been assigned to the region 4q21----qter. We determined the AGA activity in cultured fibroblasts of a girl with a 46,XX,del(4)(q33) karyotype. The results indicate that the girl is a hemizygote for AGA, permitting the assignment of human AGA to the region 4q33--- qter. PMID- 1505218 TI - Localization of the human 75-kDal Fe-S protein of NADH-coenzyme Q reductase gene (NDUFS1) to 2q33----q34. PMID- 1505219 TI - Somatic cell mapping of the human cyclophilin B gene (PPIB) to chromosome 15. AB - The polymerase chain reaction (PCR) technique was used to generate a unique probe complementary to the hydrophobic 5' end of the human cyclophilin B gene. This unique probe was hybridized to DNAs from human x hamster hybrid somatic cell lines retaining different combinations of human chromosomes. The gene was assigned to chromosome 15. PMID- 1505220 TI - Germ line-restricted supernumerary (B) chromosomes in Eptatretus okinoseanus. AB - Cytogenetic studies were performed on two types of Japanese hagfish (Eptatretus okinoseanus) that eliminate about 45% (type A) and 55% (type B) of their DNA from presumptive somatic cells during the differentiation of somatic cells. The observations revealed inter- and intraindividual variations in the number of chromosomes in germ cells of both types of hagfishes. Although the modal number of chromosomes in the germ cells was 54 in both types, the percentage of cells with the modal number was rather low (38.6% [51/132] in five specimens of type A and 22.7% [25/110] in eight specimens of type B). In addition, one of seven type B specimens clearly had a modal number of 62 chromosomes. Another specimen of type B had a bimodal distribution of chromosome numbers, with peaks of 54 and 59 chromosomes. The observation of interindividual variations was supported by data on the amount of DNA in germ cells of type B specimens. However, these variations were rarely observed in somatic cells. These results suggest that supernumerary (B) chromosomes are maintained in germ cells and are eliminated together with some other chromosomes and/or chromatin from somatic cells. PMID- 1505221 TI - Cytogenetics of bisexual/unisexual species of Poecilia. III. The karyotype of Poecilia formosa, a gynogenetic species of hybrid origin. AB - Chromosomes of the Amazon molly, Poecilia formosa, a unisexual species of hybrid origin, were investigated by C-banding, silver staining, and fluorescent staining with DAPI, quinacrine dihydrochloride, and chromomycin A3. Analysis of heterochromatin distribution indicates that chromosomes similar to the W chromosome of P. latipinna are not present in the unisexual species. Therefore, morphologically differentiated sex chromosomes do not form the basis of the unisexuality in P. formosa. The number and location of nucleolar organizer regions vary in P. formosa and do not correlate well with those of the parental species. PMID- 1505222 TI - Assignment of the NRAS protooncogene to chromosome 12 of Syrian hamster by in situ hybridization. AB - The NRAS protooncogene codes for a GTP binding/GTPase p21 protein which resides on the inner surface of the plasma membrane. Using a human cDNA probe for NRAS, we have assigned the gene to Syrian hamster chromosome 12 with the most likely localization being 12qa5. PMID- 1505223 TI - Localization of the interferon-alpha gene cluster to rat chromosome bands 5q31--- q33 by fluorescence in situ hybridization. AB - The chromosomal location of the rat interferon-alpha (IFNA) gene cluster was determined by fluorescence in situ hybridization. The fluorescent signals were localized to 5q31----q33. A previous report, using somatic cell hybrids, had suggested that the IFNA locus maps at a different region on rat chromosome 5. PMID- 1505224 TI - The persistence of chromosome translocations in a radiation worker accidentally exposed to tritium. AB - The chromosome translocation frequency in lymphocytes of an individual accidentally exposed to tritium six years previously was measured using chromosome painting. Comparisons with results from cytogenetic studies shortly after the accident indicate that the translocation frequency has remained unaltered in this individual for six years. PMID- 1505225 TI - A primate transfer RNA gene cluster and the evolution of human chromosome 1. AB - The localisation of tRNA(Asn) gene clusters in the karyotypes of primates has been studied by means of in situ hybridisation. In the human and orangutan (Pongo pygmaeus) karyotypes there are two such gene clusters, one each on the long and short arms of chromosome 1. Old World monkeys, however, contain both gene clusters on their equivalent of the human chromosome 1 short arm, which can be explained by a pericentric inversion which (amongst other chromosome changes) distinguishes the human and Old World monkey chromosomes 1. The capuchin (Cebus appella), however, a New World monkey, has only one tRNA(Asn) gene cluster, at least on the elements equivalent to human chromosome 1. This cluster is located proximal to the centromere on a chromosome that has been tentatively identified (by others) as the equivalent of the long arm of human chromosome 1. Should this prove to be correct, it would indicate that the large primate metacentric came into being in the form found today in the great apes, rather than in the form currently found in Old World monkeys. These data further show that the tRNA(Asn) gene cluster has been split in two since before the Old World monkeys and hominids diverged, i.e., over 30 million years ago, and also that the original transfer of these genes from one arm of chromosome 1 to the other was unlikely to have involved a pericentric inversion but, rather, some form of replicative transposition. PMID- 1505226 TI - Geographic patterns of chromosomal variation in South American marsh rats, Holochilus brasiliensis and H. vulpinus. AB - Karyotypes were prepared from 146 individuals, representing nine populations evenly spaced along a 2,000-km north-south transect in Paraguay and Argentina, to determine the nature, extent, and pattern of chromosomal variation in Holochilus brasiliensis chacarius and H. vulpinus. Two distinct patterns of chromosomal variation characterized these two species. In H. brasiliensis, the diploid number (2n) ranged from 48 to 56 and the nombre fondamental (NF) from 57 to 63. Four classes of chromosomal variation were found in populations of H. brasiliensis: whole-arm Robertsonian (Rb) translocations, including Rb changes with monobrachial homology, variation in the number and kind of supernumerary (B) chromosomes, centromeric rearrangements (putative pericentric inversions), and variation in the amount of euchromatin. The amount of structural variation was uniformly high in all populations of H. brasiliensis sampled, and all rearrangements appeared to be in Hardy-Weinberg proportions, corroborating the hypothesis that chromosomal rearrangements are not strongly underdominant in this species. In H. vulpinus, 2n ranged from 35 to 39 and NF from 57 to 61. Two classes of variation were found in this species: variation in the number, but not the kind, of supernumerary chromosomes and variation in the amount of euchromatin. PMID- 1505227 TI - Meiotic studies of Robertsonian polymorphisms in the South American marsh rat, Holichilus brasiliensis. AB - Meiosis was studied in male South American marsh rats (1) to help clarify the mechanisms that allow unusually high levels of Robertsonian (Rb) polymorphisms to be maintained in wild populations of these animals and (2) to test competing assumptions in two distinct models of chromosomal speciation. In both simple Rb heterozygotes and Rb heterozygotes with monobrachial homology, no univalency was observed in prophase I or metaphase I. Rates of nondisjunction were uniformly low (less than 10%) and did not differ significantly among any of the animals studied, regardless of karyotype and in contrast to the frequency of nondisjunction in other mammalian species. Robertsonian heterozygotes exhibited significantly more chiasmata than did homozygotes, largely owing to an increase in the number of terminally located chiasmata. There was a significant bias favoring the transmission of two acrocentrics over the single metacentric for some Rb rearrangements in the heterozygous state. In addition, the frequency of sex-chromosome univalency increased with increasing Rb heterozygosity, although the ratio of X- and Y-bearing secondary spermatocytes did not differ significantly from 1:1, and no secondary spermatocytes were observed that were nullisomic or disomic for an X or Y chromosome. PMID- 1505228 TI - Chromosomal rearrangements in rock wallabies, Petrogale (Marsupialia: Macropodidae). VI. Determination of the plesiomorphic karyotype: G-banding comparison of Thylogale with Petrogale persephone, P. xanthopus, and P. l. lateralis. AB - G-banding has demonstrated the presence of a conserved (2n = 22) chromosome complement in the macropod genus Thylogale and in some Petrogale species. This plesiomorphic karyotype consists of acrocentric chromosomes 1, 2, 5, 6, 8, 9, and 10; submetacentric chromosomes 3 and 4; and a metacentric chromosome 7. It should now be possible to relate the G-banding patterns of all other Petrogale species to this plesiomorphic complement and thereby determine the number and types of changes that have occurred during the course of chromosome evolution in Petrogale. It is hypothesised that this 2n = 22 complement is plesiomorphic for all macropodids. PMID- 1505229 TI - Chromosomal rearrangements in rock wallabies, Petrogale (Marsupialia: Macropodidae). VII. G-banding analysis of Petrogale brachyotis and P. concinna: species with dramatically altered karyotypes. AB - G-banded metaphase preparations of cultured fibroblasts were used to construct the karyotypes of Petrogale brachyotis (2n = 18) and P. concinna (2n = 16). The two karyotypes differ significantly from the plesiomorphic karyotype of the genus and from those of all other Petrogale species examined. Petrogale brachyotis and P. concinna are characterised by three synapomorphies: a 1-10 centric fusion, a 3a-6 centric fusion, and a submetacentric chromosome 2 (2s). Both species also possess autapomorphies. Petrogale brachyotis is characterised by submetacentric chromosomes 5 (5s) and 4 (4sm), whereas P. concinna is characterised by a 5-9 centric fusion and a submetacentric chromosome 8 (8m). The 2s, 5s, 4sm, and 8m chromosomes all appear to be derived from their plesiomorphic homologs by centromeric transpositions. Although the rate of chromosome evolution varies considerably in Petrogale, the genus clearly exhibits karyotypic orthoselection, with all the autosomal rearrangements identified being either centric fusions or centromeric transpositions. This study also illustrates the potential for convergent evolution in chromosomally diverse groups and demonstrates the importance of G-banding studies for accurate identification of chromosome rearrangements. PMID- 1505230 TI - Synapsis, recombination, and meiotic segregation in the mesquite lizard, Sceloporus grammicus, complex. I. Pericentric inversion heteromorphism of the F5 cytotype. AB - Chromosomal pairing and recombination were analyzed in male specimens of Sceloporus grammicus heterozygous for a large pericentric inversion of macrochromosome 4. Analysis of silver-stained synaptonemal complexes (SCs) in surface-spread nuclei revealed that homologously paired inversion loops were not formed. Synapsis of the inverted segments proceeded directly to nonhomologous straight pairing. In some nuclei, this resulted in a configuration that could not be distinguished from homozygous bivalents of similar size. Examination of Giemsa and silver-stained diakinetic nuclei indicated that crossing-over was limited to the noninverted (homologous) portion of the heteromorphic bivalent. Analysis of secondary spermatocytes (metaphase II configurations) revealed normal disjunction and balanced segregation of the elements of the heteromorphic bivalent. These observations indicate that the inversion heteromorphism does not lead to the production of unbalanced gametes. PMID- 1505231 TI - Synapsis, recombination, and meiotic segregation in the mesquite lizard, Sceloporus grammicus, complex. II. Fission heteromorphism of the FM2 cytotype and evolution of chromosome 2. AB - Somatic and meiotic chromosomal and synaptonemal complex techniques were used to characterize the chromosomal complement and to study the fission heteromorphism of chromosome 4 in the FM2 cytotype of Sceloporus grammicus. Analysis of silver stained somatic metaphases revealed that the nucleolar organizer region in this cytotype is located at the distal end of a pair of medium-sized acrocentric chromosomes, rather than on the largest acrocentric chromosomal pair, as previously reported. This condition is hypothesized to be the result of at least two sequential rearrangements. Analysis of surface-spread zygotene and pachytene nuclei indicated that the components of the chromosome 4 trivalent initiated synapsis at their distal telomeric regions. Although synapsis of the fission trivalent was synchronous with that of the homomorphic autosomal pairs, completion of synapsis was delayed in the trivalent. Associations between the fission trivalent and other autosomal or sex-chromosomal elements occurred in approximately one third of the pachytene nuclei examined. Analysis of secondary spermatocytes (metaphase II configurations) revealed low levels of nondisjunction in fission heterozygotes. These analyses indicate that FM2 individuals heterozygous for the fission rearrangement of chromosome 4 suffer no meiotic deficit. PMID- 1505232 TI - Interstitial hybridization sites of the (TTAGGG)n telomeric sequence on the chromosomes of some North American hylid frogs. AB - Interstitial hybridization sites for the (TTAGGG)n telomeric repeat sequence were present in all seven species of hylid frogs examined and in a triploid hybrid between two of the species. Intra- and interspecific differences and similarities in hybridization sites agreed with what is known about the systematics of these species. Chromosome fusions, fissions, and inversions do not appear to have played a role in the evolution of the interstitial sites for the telomeric repeat in the species examined. PMID- 1505233 TI - Identification of equine chromosomes in horse x mouse somatic cell hybrids. AB - Giemsa-11 (G-11) staining and in situ hybridization were used to identify the equine chromosome complement of horse x mouse somatic cell hybrids. The presence of horse chromosomes in somatic cell hybrids was determined by differential G-11 staining. The slides were then destained and hybridized with biotinylated total horse (Equus caballus) genomic DNA without suppression. Fluorescence detection permitted rapid confirmation of horse chromosomal DNA in the hybrid cells. PMID- 1505234 TI - Sperm age, sex ratio, and hyperhaploidy frequency in mice. AB - Physiologically aged and unaged sperm from each of 12 sexually mature B6SJLF1/J mice were used to fertilize oocytes from females of the same strain, with each male serving as its own control. Male genomes in 323 and 307 first-cleavage metaphases obtained by in vivo and in vitro fertilization, respectively, were analyzed cytogenetically, using C-banding for detection of the Y chromosome. The sex (X:Y) ratio among all zygotes resulting from in vivo fertilization was 1.18; in zygotes resulting from in vivo fertilization by aged (14-d mating intervals) sperm, however, the ratio was 1.53, which differed significantly (chi 2 = 6.72, P less than 0.01) from the theoretical value of 1.00. Comparison of the sex ratio in zygotes resulting from in vivo fertilization by unaged sperm (3-d mating intervals), 0.94, with that in zygotes resulting from fertilization by aged sperm (using a 2 x 2 contingency table) showed a significant (chi c2 = 4.19, P less than 0.05) relationship between sex ratio and sperm age. In vitro neither the combined nor the individual 3- and 14-d data deviated significantly from the expected sex ratio of 1.00. The frequency of sperm-derived hyperhaploidy did not differ significantly between the in vivo (3.4%) and in vitro (5.9%) populations, but did between unaged (2.5%) and aged (6.8%) sperm (chi c2 = 5.74, P less than 0.01). All hyperhaploid zygotes had a complement of n + 1 chromosomes, except the 14-d in vitro group, where complements of n + 2 and n + 3 chromosomes were seen. Sperm-derived polyploidy, which was observed only in the in vitro group, was independent of sperm age and occurred in 6.8% of the zygotes. These data provide support for the sperm-aging hypothesis and indicate, for the first time, an influence of sperm aging in the male genital tract on the X:Y ratio of conceptuses resulting from natural matings of chromosomally normal males. PMID- 1505235 TI - Linkage of two enzyme loci in the fish genus Poecilia (Teleostei:Poeciliidae). AB - The linkage of loci coding for glucose-6-phosphate dehydrogenase (G6PD) and phosphogluconate dehydrogenase (PGD) is described in fish of the genus Poecilia (Teleostei:Poeciliidae) and designated Poecilia linkage group I. These two loci were shown to assort independently from six other informative markers (peptidase S, malate dehydrogenase 2 [soluble], mannose phosphate isomerase, parvalbumin 2, phosphoglucomutase, and glyceraldehyde-3-phosphate dehydrogenase 2) within the limits of the data obtained. Data for the linkage analyses were generated by scoring starch-gel electrophoretic phenotypes of the eight loci in reciprocal backcross hybrids obtained from matings between Poecilia perugiae and P. vittata. The linkage chi 2 for G6PD-PGD locus pairs was significant (P less than 0.001) in all reciprocal backcross hybrid broods (22.7% recombinants in the combined data), indicating linkage in both parental species. The linkage of G6PD and PGD in gene maps of the poeciliid genera Xiphophorus and Poeciliopsis documents homology of this linkage within the family. Linkages in salmonid and centrarchid fishes suggest conservation of this linkage group in most or all teleosts. The six additional indpendently assorting loci have been assigned to independent linkage groups in Xiphophorus; thus, no example of poeciliid linkage group divergence has yet been identified. PMID- 1505236 TI - Absence of satellite III DNA in the centromere and the proximal long-arm region of human chromosome 14: analysis of a 14p- variant. AB - Cytogenetic methods and molecular probes derived from the centromere and short arm of chromosome 14 were used to investigate the structural properties of a chromosome 14 variant. Results of GTL, CBG, Ag-NOR, and non-banded Giemsa staining of the chromosomes suggested the complete absence of the short arm and possibly a large part of the centromere. Negative in situ hybridisation with an alpha satellite III probe confirmed the absence of the arm; the detection of normal amounts of alpha satellite DNA, however, indicated retention of the centromeric domain. The natural occurrence of a human acrocentric variant lacking a short arm was thus established. Within the detection limits of the methods used, the results demonstrate that satellite III DNA is not essential for normal centromeric activity and allow us to exclude the presence of this satellite DNA within the centromere and proximal long-arm region of human chromosome 14. PMID- 1505237 TI - In situ hybridisation localises the gene for the major intrinsic protein of eye lens fibre cell membranes to human chromosome 12q14. AB - The gene encoding the major intrinsic protein (MIP) of eye lens fibre cell membranes has been localised to human chromosome 12q14 by in situ hybridisation of a cDNA for rat MIP to G-banded metaphase chromosomes. The human MIP gene maps within a conserved region of synteny with mouse Chromosome 10. PMID- 1505238 TI - Measuring bilingual children's receptive vocabularies. AB - Receptive vocabulary of Hispanic children in Miami was tested in both English and Spanish with complementary standardized tests, the Peabody Picture Vocabulary Test (PPVT-R) and the Test de Vocabulario en Imagenes Peabody (TVIP-H). 105 bilingual first graders, of middle to high socioeconomic status relative to national norms, were divided according to the language(s) spoken in their homes. Both groups, whether they spoke only Spanish in the home (OSH) or both English and Spanish in the home (ESH), performed near the mean of 100 in Spanish receptive vocabulary (TVIP-H means 97.0 and 96.5); in contrast, ESH group children scored more than 1 SD higher in English than OSH group children (PPVT-R means 88.0 and 69.7, respectively). It appears, therefore, that learning 2 languages at once does not harm receptive language development in the language of origin, while it does lay the groundwork for superior performance in the majority language. Furthermore, an analysis of translation equivalents, items shared by both tests, shows that a statistically significant portion of bilingual children's lexical knowledge does not overlap in their 2 languages and is therefore not reflected in single-language scores. PMID- 1505239 TI - Influences of witnessed affect on information processing in children. AB - Children between the ages of 5 and 10 years watched a videotape of a child having a routine medical exam. Embedded within the scenes were systematic variations of depicted facial affect shown by doctor and child. Measures were taken of autonomic reactions and information-processing errors in response to positive, neutral, and negative affective cues. For 5-6-year-olds, processing errors were greatest in the negative affect condition. Additionally, peak increases in heart rate (HR) and skin conductance level (SCL) were demonstrated by 5-6-year-olds in response to negative affect shown by the witnessed child; increases in HR were in turn predictive of processing errors. Older children (9-10 years) showed trends reflecting reduced processing errors in response to witnessed negative affect. It was suggested that younger children respond to salient threat cues with a "defensive" response pattern that is relatively adaptive at younger but not older ages. PMID- 1505240 TI - Intermodal perception of happy and angry expressive behaviors by seven-month-old infants. AB - 2 studies were conducted to examine the roles of facial motion and temporal correspondences in the intermodal perception of happy and angry expressive events. 7-month-old infants saw 2 video facial expressions and heard a single vocal expression characteristic of one of the facial expressions. Infants saw either a normally lighted face (fully illuminated condition) or a moving dot display of a face (point light condition). In Study 1, one woman expressed the affects vocally, another woman expressed the affects facially, and what they said also differed. Infants in the point light condition showed a reliable preference for the affectively concordant displays, while infants in the fully illuminated condition showed no preference for the affectively concordant display. In a second study, the visual and vocal displays were produced by a single individual on one occasion and were presented to infants 5 sec out of synchrony. Infants in both conditions looked longer at the affectively concordant displays. The results of the 2 studies indicate that infants can discriminate happy and angry affective expressions on the basis of motion information, and that the temporal correspondences unifying these affective events may be affect-specific rhythms. PMID- 1505241 TI - Responses to the negative emotions of others by autistic, mentally retarded, and normal children. AB - Attention, facial affect, and behavioral responses to adults showing distress, fear, and discomfort were compared for autistic, mentally retarded, and normal children. The normal and mentally retarded children were very attentive to adults in all 3 situations. In contrast, many of the autistic children appeared to ignore or not notice the adults showing these negative affects. As a group, the autistic children looked at the adults less and were much more engaged in toy play than the other children during periods when an adult pretended to be hurt. The autistic children were also less attentive to adults showing fear, although their behavior was not different from the normal children. Few of the children in any group showed much facial affect in response to these situations. The results are discussed in terms of the importance of affect in the social learning experiences of the young child. PMID- 1505242 TI - Maternal responsiveness to infants in three societies: the United States, France, and Japan. AB - This study examines and compares prominent characteristics of maternal responsiveness to infant activity during home-based naturalistic interactions of mother-infant dyads in New York City, Paris, and Tokyo. Both culture-general and culture-specific patterns of responsiveness emerged. For example, in all 3 locales infants behaved similarly, mothers also behaved similarly with respect to a hierarchy of response types, and mothers and infants manifest both specificity and mutual appropriateness in their interactions: Mothers responded to infants' exploration of the environment with encouragement to the environment, to infants' vocalizing nondistress with imitation, and to infants' vocalizing distress with nurturance. Differences in maternal responsiveness among cultures occurred to infant looking rather than to infant vocalizing and in mothers' emphasizing dyadic versus extradyadic loci of interaction. Universals of maternal responsiveness, potential sources of cultural variation, and implications of similarities and differences in responsiveness for child development in different cultural contexts are discussed. PMID- 1505244 TI - Children's relationships with caregivers: mothers and child care teachers. AB - Infant, toddler, and preschool children's relationships with mothers and teachers were examined in this study. 110 children were observed with their mothers during child care arrivals and reunions. 403 children were observed with their teachers in child care. 3 categories of relationships were derived from these observations. Children in the secure relationship category experienced more teacher involvement than children in the avoidant or ambivalent relationship categories. Children in the ambivalent relationship categories experienced more teacher involvement than children in avoidant relationship categories. A subsample (n = 23) of children were seen with their mothers both during child care arrivals and reunions and in the Strange Situation. Relationship classifications were similar. PMID- 1505243 TI - The influence of culturally derived values on Anglo and Puerto Rican mothers' perceptions of attachment behavior. AB - This 2-part investigation examined indigenous concepts of desirable and undesirable attachment behavior among middle- and lower-class Anglo and lower class Puerto Rican mothers in order to formulate culturally sensitive criteria of normative attachment behavior. Study 1 elicited indigenous concepts of desirable and undesirable attachment behavior using open-ended probes. On the basis of mothers' responses in Study 1, culturally sensitive vignettes of desirable and undesirable attachment behavior were constructed, and culturally relevant descriptors of toddler characteristics were selected. In Study 2, mothers' perceptions of the hypothetical toddlers were compared using the selected descriptors. The findings indicate that, whereas the Anglo mothers focus more on characteristics associated with the presence or absence of individual autonomy, the Puerto Rican mothers place more emphasis on the child's ability to maintain proper demeanor in a public context. These findings were coherent across mothers': (a) open-ended conceptualizations, (b) desirability ratings, and (c) descriptor ratings of the toddlers. PMID- 1505245 TI - Children's relationships with child care teachers: stability and concordance with parental attachments. AB - In order to examine caregiving relationships of children enrolled in childcare, two longitudinal samples of children, n = 72 and n = 106, were followed from infancy through preschool. Maternal attachment as assessed by the Strange Situation, 4-year-old reunion behavior, and by the Attachment Q-Set tended to be stable across time. Children's teacher-child relationship quality, as measured by the Attachment Q-Set, was stable if the teacher remained the same. When the teacher changed, teacher-child relationship quality tended to be unstable until the children were 30 months old. After 30 months, relationship quality with teachers tended to be stable regardless of whether or not the teacher changed. Maternal and teacher relationships were nonconcordant. There were few interactions between adult caregiver relationship quality and age of entry into child care or intensity of child care. PMID- 1505246 TI - Maternal and paternal disciplinary styles: relations with preschoolers' playground behavioral orientations and peer status. AB - To explore relations among parents' self-reported disciplinary styles, preschoolers' playground behavioral orientations, and peer status, 106 mothers and fathers of preschool-age children (age range = 40-71 months) participated in home disciplinary style interviews. Observations of their children's playground behavior in preschool settings and measures of sociometric status were also obtained. Results indicated that children of more inductive mothers and fathers (i.e., less power assertive) exhibited fewer disruptive playground behaviors. In addition, daughters and older preschoolers of inductive mothers exhibited more prosocial behavior. Children of inductive mothers were also more preferred by peers. Few significant relations were found between paternal discipline and child behavior/peer status. Age-related patterns of behavior also indicated that older preschoolers who engaged in more prosocial and less antisocial and disruptive playground behavior were more preferred by peers. In addition, child behaviors were found to mediate maternal discipline and peer status. PMID- 1505247 TI - Victimizers and their victims: children's conceptions of the mixed emotional consequences of moral transgressions. AB - 4-8-year-old children's conceptions of the emotional consequences of moral transgressions were assessed in 2 experiments. In Experiment 1, most children expected victimizers to feel positive emotions and victims to feel negative emotions, but 8-year-olds who assessed victims first subsequently attributed less positive emotions to victimizers. Despite efforts to manipulate the salience of victims' losses in Experiment 2, children had similar expectations about the emotional consequences of transgressions. However, a developmental shift emerged: 4-year-olds attributed extremely positive emotions to victimizers due to the material gains produced by victimization, whereas 8-year-olds attributed less positive emotions to victimizers, in part due to the unfairness and harm produced by victimization. Probe questions revealed that older children also attributed additional negative-valence emotions to victimizers, suggesting that victimizers are expected to feel conflicting rather than exclusively positive emotions. Discussion focused on potential cognitive constraints in children's conceptions of moral emotions. PMID- 1505248 TI - Visual attention to and comprehension of television in attention-deficit hyperactivity disordered and normal boys. AB - This study examined the effects of distracters on the television viewing of diagnosed ADHD (n = 19) and normal (n = 20) boys who ranged in age from 6 to 12 years. Subjects were videotaped watching four 7-min segments of "3-2-1 Contact," once in the presence and once in the absence of highly appealing toys. The results indicated that, while in the presence of toys, ADHD boys spent one-half as much time as control boys attending to the television. However, when toys were absent, there were no significant differences in visual attention between ADHD and normal boys. The effect of the toy manipulation was most dramatic with younger children of both groups. Recall of didactic content by ADHD boys and normal subjects did not differ significantly, even when the attention of ADHD boys was reduced. These findings suggest that ADHD children, like their normal counterparts, are active and strategic viewers of television. PMID- 1505249 TI - Effects of early and recent maternal employment on children from low-income families. AB - The effects of early maternal employment (employment during the child's first 3 years) and recent maternal employment (employment during the previous 3 years) on 189 second-grade children from low-income families were examined. Maternal employment was related to a number of selection factors. In comparison to mothers who were not employed, employed mothers scored higher on a mental aptitude test and were more highly educated. Both early and recent maternal employment were also associated with measures of the current family functioning: there was less poverty and higher HOME environment scores when mothers were employed. Hierarchical multiple regressions showed that children's math achievement was positively predicted by early maternal employment and children's reading achievement was positively predicted by recent maternal employment, even after controlling for selection effects and current family environment. These results are discussed in terms of possible mechanisms by which maternal employment may affect children's development. PMID- 1505250 TI - Children's awareness of the biological implications of kinship. AB - Preschoolers' thinking about kinship was explored by means of a simple induction task. A target animal was described as possessing a property, and children were asked whether each of 2 other animals shares the property or not. When no information about kinship was given, children in Experiment 1 based their inductions of biological properties on physical similarity. However, when kinship relations were specified, children judged that dissimilar-looking kin share more biological properties than similar-looking but unrelated members of the same species. In Experiment 2, describing the similar animals as socially related did not change the basic pattern of inductions obtained in the first experiment. Moreover, subjects in Experiment 3 did not induce more acquired physical and psychological properties among families than among unrelated animals. The results of Experiments 1 and 2 illustrate one case where young children favor a nonperceptible relation (kinship) over a perceptible one (similarity) as a basis for judgment. The overall pattern of data suggest that young children distinguish to some extent between the biological and social domains. PMID- 1505251 TI - Young children's understanding of different types of beliefs. AB - The purpose of this investigation was to see whether children's understandings of different types of beliefs develop concurrently. Children of 3, 4, and 5 years of age were told or shown that child story characters held beliefs different from their own or from one another, not only concerning matters of physical fact ("false beliefs"), but also concerning morality, social convention, value, and ownership of property. In contrast to the older subjects, most 3-year-olds had difficulty in attributing to others deviant beliefs of all types, except perhaps ownership, sometimes even after having been told repeatedly what the other child believed. In addition, intercorrelations among different belief tasks were positive and substantial. It was suggested that an emerging representational conception of the mind is what enables older preschoolers to understand the possibility of belief differences of all these types. PMID- 1505252 TI - A reading-level design study of phonological skills underlying fourth-grade children's word reading difficulties. AB - A 3-group reading-level design was used to investigate phonological analysis, verbal working memory, and pseudoword reading performance in less skilled fourth grade readers. Children were given phonological oddity tasks assessing their sensitivity to subsyllabic and phonemic units, together with standardized tests of verbal working memory and pseudoword reading. Less skilled fourth-grade readers performed lower than both chronological age and reading-level controls on the phonological oddity and pseudoword reading tests. Less skilled fourth-grade readers performed at the same level as skilled second-grade readers on a test of verbal working memory. Skilled fourth-grade readers scored higher than both other groups on this test. Correlational analyses were consistent with the view that phonological analysis skills contribute more strongly than verbal working memory skills to children's decoding abilities. PMID- 1505253 TI - [Results of a consensus conference on the topic, "Homologous blood saving methods in surgical medicine"]. PMID- 1505254 TI - [Ambulatory surgery--an alternative to inpatient treatment]. PMID- 1505255 TI - [Experiences in ambulatory surgery: anesthesia procedures]. PMID- 1505256 TI - [Ambulatory pediatric surgery--indications, results and limits]. PMID- 1505257 TI - [Ambulatory surgery of inguinal hernia in adults. A 4-year report of experiences with 89 patients]. PMID- 1505258 TI - [Ambulatory surgery between motivation and frustration]. PMID- 1505259 TI - [The surgeon Johann Friedrich Dieffenbach and his effect on the development of plastic surgery]. PMID- 1505260 TI - [Diagnostic strategies in malignant occlusive jaundice]. PMID- 1505261 TI - [Interventional non-surgical drainage techniques in proximal bile duct tumors]. PMID- 1505262 TI - [Pulmonary complications following surgical abdominal interventions. Identification of various risk groups]. AB - Incidence and type of postoperative complications were prospectively analyzed in 2280 patients undergoing gastrointestinal surgery. 6.6% had one or more pulmonary complications requiring therapeutic intervention (2.3% pneumonia, 1.6% drained pleural effusions, 1.2% atelectases). Based on univariate and logistic regression analyses, the following parameters constitute high-risk patients with regard to pulmonary complications: Elective surgery (4.3%, 61/1428): anemia (7.2% pulmonary complications), pathological blood gas analysis (9.8%), preoperative hospitalization greater than 1 week (6.3%), blood loss under operations greater than 1000 ml (10.5%), length of the operation greater than 3 h (9.7%); emergency surgery (10.4%, 89/852): upper gastrointestinal operation (16.2%), age greater than 75 (19.9%), ASA IV/V (28%), anemia (19.6%), chronic bronchitis (19%), pathological blood gas analysis (26.6%), diabetes (16.5%), heart failure (18.2%), blood loss under operation greater than 1000 ml (24.3%), length of the operation greater than 2 h (15.4%). These results allow to distinguish between different levels of pulmonary risk. PMID- 1505263 TI - [Initial results of minimally invasive lung surgery]. AB - From June 1991-February 1992 we have performed in 10 patients wedge resection of the lung by means of minimally invasive surgery. Indications were: spontaneous pneumothorax (5), tumours (3), suspected systemic disease (2). In all patients the pathological specimen preoperatively diagnosed by x-ray and CT, could be harvested without any problem. Minimally invasive, atypical wedge resection is considered as an effective procedure with low risk and discomfort for the patient. PMID- 1505264 TI - [Routine drainage following uncomplicated, elective cholecystectomy? A prospective, randomized study]. AB - A prospective randomized and controlled study of prophylactic drainage after simple, elective cholecystectomy was carried out. From March 1988 to June 1991 80 patients received an Easy-Flow drain and 80 did not. Operation and perioperative management were standardized. The endpoint of the study was postoperative morbidity, especially postoperative pyrexia and subhepatic fluid collection. The latter was identified by ultrasonography performed daily on postoperative day 1 4. No patient died. The morbidity including postoperative pyrexia revealed no difference between drained and undrained patients. In 19 of the patients with (23.8%) and in 25 of the patients without drainage (31.3%) a subhepatic fluid collection could be demonstrated by ultrasonography. This difference was not statistically significant either. We conclude that prophylactic drainage after elective, simple cholecystectomy is of no use for the patient. As subhepatic fluid collections can be seen in drained as well as in undrained patients it has to be accepted that drainage does not guarantee the removal of subhepatic fluid. Therefore its indicatory function (bleeding) and the ability to prevent the patient having biliary peritonitis or local abscess has to be put in doubt. PMID- 1505265 TI - [Complications of diverticuli of the proximal small intestine. 3 case reports and review of the literature]. AB - Three cases of small bowel diverticula are presented. In the first patient perforation of a congenital diverticulum in pars II of the duodenum occurred, the second case is the first description of bezoar in a duodenal diverticulum with bleeding of the diverticulum at the same time and the third patient suffered from ileus due to unusually large jejunal diverticulum. Up to 20% of all autopsied patients present duodenal diverticula. In other parts of small bowel diverticula are not as frequent. Most cases are asymptomatic and require no treatment. As soon as ailments occur, further investigations and probably surgical treatment is necessary. Perforation, bleeding and obstruction are indications for surgical interventions. The symptomatology is unspecific, therefore preoperative diagnosis is difficult. At least during the operation the possibility of small bowel diverticula and their complications should be considered. Till today complications of small bowel diverticula are affected with a mortality of 33-48%. More awareness of their existence could possibly improve this unfavourable outcome. PMID- 1505266 TI - [Rupture of the Achilles tendon--fibrin gluing or suture?]. AB - The rise of recreational sports activities and the incidence of ruptures of the Achilles tendons has increased simultaneously. Recently the use of fibrin sealing for surgical therapy of ruptured Achilles tendons has emerged as an alternative technique. Between 1982 and 1989 62 consecutive patients were operated for unilateral Achilles tendon rupture. Following causes for ruptures are known: 36 indirect traumas in sport (74%), 9 direct blunt injuries at occupational work (18%), 3 traffic-accidents (11%) and 1 rupture after operation of a Haglund exostosis. 25 patients (56%) were treated by suture technique and 20 patients (44%) with fibrin sealant. The mean long term follow-up of 49 months is known of 49 patients. There were 3 (12%) postoperative infections in the suture group and none in the fibrin group. After suturing the Achilles tendon 3 (12%) reruptures occurred 8-10 weeks after tendon repair and 1 (5%) rerupture after fibrin sealing. All reruptures are caused by a new adequate trauma. The time of return to social and recreational activities was 9 months in the suture group and 7 months in the fibrin group. The functional and cosmetic results after use of fibrin was significant better, and the long-term results were very satisfactory. We prefer fibrin sealing for the treatment of acute ruptures of Achilles tendons. PMID- 1505267 TI - [Compartment resection as therapy of choice in subfascial soft tissue sarcoma exemplified by the thigh]. AB - Soft-tissue sarcomas tend to have local recurrences after inadequate therapy. So reactions with wide margins are required. If a sarcoma is localized subfascially, such wide margins are often hard to achieve in a "wide resection". Concerning the growth behavior of soft-tissue sarcomas and the intraoperative orientation it makes more sense to resect these tumors with their whole anatomical compartment. This kind of operation is described by the three large compartmental resections of the thigh. PMID- 1505268 TI - [Arterio-mesenteric duodenal obstruction]. PMID- 1505269 TI - [Two-step removal of a large retrocaval pheochromocytoma with temporary veno venous bypass]. PMID- 1505270 TI - [Causes of maternal death. A 10-year case analysis]. AB - The causes of maternal deaths in our hospital from 1981 to 1989 were analysed. There were 12,819 live births and 6 maternal deaths during this period, a maternal mortality rate of 46.69/per 100,000. The main cause of maternal deaths was acute fatty liver of pregnancy (50%), and next cardiac disease, acute hemorrhagic necrotic pancreatitis and hemorrhage of subarachnoid space (each 16.67%). There was no death due to obstetric hemorrhage, pregnancy induced hypertension syndrome or ectopic pregnancy. It is suggested that needle biopsy of the liver should be done for pregnant women with jaundice of unknown cause. Pregnant women with cardiac disease should be under the care of both obstetrician and internist in collaboration and cesarean section is indicated when the woman's cardiac function remains at grade 3 or 4. PMID- 1505271 TI - [Fetal umbilical arterial blood flow velocity waveforms as measured in the uterus by pulsed Doppler and B-mode ultrasound]. AB - 3.0 MHz Doppler ultrasound was used to measure the umbilical arterial blood flow velocity waveforms (FVW) in 174 fetuses between 22-42 weeks of gestation. The A/B ratio (systolic/diastolic), resistance index (RI), pulsatility index (PI) and impedance index (ImI) were used as indexes of placental flow resistance. In normal pregnancy (n = 152), 460 measurements were performed. Analysis of these waveforms demonstrated that the placental is an organ of low vascular resistance and that placental resistance to blood flow gradually declines with advancing gestational age. Our results indicated a significant negative correlation between each of the four indexes and gestational age. There was a small but significant decrease in all four indexes, from 22-42 weeks. 56 scans were performed on 22 fetuses with intrauterine growth retardation (IUGR). The sonograms from these IUGR fetuses showed different characteristics which implied a high distal impedance to the blood flow. 16 of these (72.7%) presented an abnormal increase in all four indexes. PMID- 1505272 TI - [Modified method of determining phosphatidylglycerol in amniotic fluid to assess fetal maturity]. AB - In this study the amniotic fluid of 111 cases were analyzed to assess fetal maturity by a modified method of determining phosphatidylglycerol. The L/S ratio was also determined in the amniotic fluid by thin layer chromatography at the same time. This method was found especially valuable where the L/S ratio was not less than 2.0 and the newborn infant did not have RDS. Here the fetal maturation was characterized by an early appearance of PG. Clinical evaluation showed that the rate of accuracy to assess fetal maturity of PG was 97.3%, significantly higher when compared with the 86.5% by L/S ratio (P less than 0.01). The false negative rate for PG was 5%. PG analysis in amniotic fluid as markers of surfactant seems to be of value as an additional index of prenatal evaluation of lung maturity. The modified method of PG assessment in amniotic fluid is a better method for estimating fetal maturity. PMID- 1505273 TI - [Preterm delivery and its risk factors]. AB - A case-control study on preterm delivery was conducted in Jianan and Jianhan District, Wuhan City in 1988. 130 singleton preterm infants were included with 260 term infants as control. The results showed that the risk factors in prematurity were edema-proteinuria-hypertension syndrome (OR 1.8), maternal diseases in pregnancy (OR 1.6), hyperemesis gravidarum (OR 5.1), vaginal bleeding during pregnancy (OR 2.4), premature rupture of membranes (OR 3.6), low weight gain and low average weight gain per week during pregnancy, psychosocial stress during pregnancy, inadequate prenatal care, maternal stature less than 158 cm (OR 1.7), menarche before age 12 (OR 4.3), multi-gravida (OR 2.1), previous induced abortion (OR 2.1) and passive cigarette smoking during pregnancy. The author suggests that early treatment of complications of pregnancy and forcing prenatal care should be emphasized in order to reduce the incidence of preterm births. PMID- 1505274 TI - [Prenatal diagnosis of fetal cardiac disease with echocardiography. National Group for Fetal Echocardiography]. AB - M-mode, 2DE and PDE were performed on 630 fetuses of high risk pregnancies. Fetal gestation ages ranged from 16 to 41 weeks. 21 cases of fetal heart disease were detected during pregnancy. The detected rate of fetal cardiac disease with echocardiography in high-risk pregnancies was 3.3%. In total 21 cases of fetal cardiac disease including 3 cases of atrial septal defect, 5 ventricular septal defect, 3 fetal non-immuno hydrops with pericardial effusion, 2 atrioventricular canal defect, 2 cardiac tumor (one rhabdomyoma, another lipoblastoma), an endocardial fibroelastosis, pulmonary stenosis, a single atrium with single ventricle, a hypoplastic left ventricle with single atrium and pulmonary atresia, a hypoplastic right ventricle with pulmonary atresia and a truncus arteriosus were found. 19 cases of fetal cardiac disease were confirmed at autopsy and other two by auscultation and echocardiography after delivery. The significant high risk factors were bradycardia in 6 cases, non-immuno hydrops in 5 cases and virus infection at early pregnancy in 3 cases. CONCLUSION: (1) 2DE and PDE are the most valuable non-invasive technique for detection of fetal structural cardiac abnormalities. (2) Sustained bradycardia, non-immuno hydrops and virus infection at early pregnancy were the significant high-risk factors of fetal heart disease. Fetal non-immuno hydrops may present congestive cardiac failure in the uterus. PMID- 1505275 TI - [Experiences with bromocriptine treatment of female infertility due to hyperprolactinemia]. AB - From July 1981 to September 1988, 106 infertile patients with hyperprolactinemia treated with bromocriptine were reviewed retrospectively with special attention to the dosage of bromocriptine and the evaluation of infertility before treatment 84 patients (79.2%) became pregnant. The patients were divided into 3 groups according to the following doses of bromocriptine: 7.5, 5.0, and less than 5.0 mg/day. The pregnancy rate was 90.7%, 84.6%, and 66.7% respectively with the highest at 7.5mg/day, which was significantly higher than that at less than 5.0mg/day (P less than 0.02). The average duration from treatment to pregnancy was 3.6, 3.4, and 7.4 months respectively. The duration in the less than 5mg/day group was twice that in the other two groups. 84.5% of the pregnancies occurred within 6 months of treatment. Pretreatment of organic lesions and additional therapy for induction of ovulation were given to 29.8% of patients who later became pregnant. Systematic evaluation of the causes of infertility other than hyperprolactinemia before the use of bromocriptine and an optimal dose of 5 7.5mg/day will give the best results. PMID- 1505276 TI - [Cisplatin nephrotoxicity: clinical observation and animal experiment]. AB - Animal experiment and clinical observation were carried out to study the nephrotoxicity of cisplatin in order to give protective measures. In animal experiment it had been demonstrated that the nephrotoxicity induced by cisplatin was mainly related to the intraperitoneal concentration of cisplatin. The nephrotoxicity was permanent in rats treated with cumulative cisplatin. The main pathologic lesions were characterized by interstitial hyperemia, degeneration of the tubular cells and formation of tubular casts. In a Clinical study to compare two preventive methods (sodium thiosulfate and hydration) from cisplatin induced nephrotoxicity, the BUN and serum Cr were measured in 28 patients. The results revealed that there was no significant difference between the two groups (P greater than 0.05). The two protective measures had similar effect in reducing the nephrotoxicity of cisplatin. Five of 6 patients treated with cisplatin developed hypo-magnesemia but only one had symptoms. PMID- 1505277 TI - [Cervical ripening and drug dilatation for birth control operations]. AB - Cervical ripening in induced labor at second trimester of pregnancy was studied in 81 cases. The method consisted of injecting diazepam gel through Foley's catheter, into the extra-amniotic space, and at the level of cervical internal os. The cervix was found to be softened, the time interval between induction and onset of labor shortened and there was no cervical laceration. A comparison between the experimental and control groups showed significant difference. The use of suppositories for cervical dilatation in 719 cases of induced abortion and 34 cases of insertion and/or removal of IUD was also studied. The results were satisfactory. The mechanism of cervical dilatation and ripening with drug had been investigated at different periods of pregnancy and in non-pregnant women as well. PMID- 1505278 TI - [Clinical uses of Doppler ultrasound in the measurement of fetal umbilical blood flow and uterine blood flow velocity]. PMID- 1505279 TI - [Effect of 3,4-dihydroxyacetophenone on platelet aggregation in normal pregnancy and pregnancy induced hypertension]. AB - The effect of 3,4-Dihydroxyacetophenone (DHAP) on platelet aggregation in normal pregnancy and pregnancy induced hypertension (PIH) in the third-trimester was studied by optical method. The IC50 values of DHAP in inhibiting ADP-induced platelet aggregation in normal pregnancy and PIH were 1.0 x 10(-3) mol/L and 2.4 x 10(-3) mol/L respectively. A dose-effect relationship of DHAP was also demonstrated (r greater than 0.92). At various time-phases of ADP-induced platelet aggregation, the addition of DHAP to the platelet-rich plasma could rapidly decrease the two-phase aggregation. DHAP of 200-240 mg/d x 3-5 days by i.v. drips given to patients with PIH also inhibited ADP-induced platelet aggregation. The authors conclude that DHAP is a potent antithrombogenic agent both in vitro and in vivo and is therefore a promising drug to improve utero placenta-fetal circulation. PMID- 1505280 TI - Gastric acid secretion and gastrin release in the baboon. AB - Significant species differences have been demonstrated in gastric physiology, a factor that limits extrapolation of animal data to man. Primate physiology is thought to be similar to that of man; however, gastric function has not been adequately documented in the primate. In the present study six baboons (body weight 25.5 +/- 1.8 kg) were trained to sit in a chair and gastric acid secretion and gastrin release was studied in conscious animals. Mean basal acid secretion was 1.3 +/- 0.1 mmol (H+)/hr. Maximum output after pentagastrin (12 micrograms/kg/hr) was 9.5 +/- 0.9 mmol (H+)/hr and 11.0 +/- 0.4 mmol (H+)/hr after histamine (40 micrograms/kg/hr). A statistically significant (by cosinor analysis) circadian rhythm was demonstrated for intragastric pH over 24 hr in fasted baboons (P less than 0.001). Mean basal serum gastrin level was 37.7 +/- 8.3 pg/ml. The integrated gastrin response after administration of a protein rich meal was 2.52 +/- 0.07 ng x min/ml and this increased to 5.17 +/- 0.18 ng x min/ml (P less than 0.05) following simultaneous administration of a meal with atropine (0.2 mg/kg) (P less than 0.05). Our results suggest that there is significant basal and stimulated acid secretion in the baboon; the amount of acid secreted is similar to that reported in man. Gastric pH demonstrated a circadian rhythm. Postprandial gastrin release was significantly enhanced by cotreatment with atropine. As the present findings are similar to those previously reported in man, the baboon may be a useful model for further studies in gastric physiology and experimental peptic ulceration. PMID- 1505281 TI - Effect of hepatic collateral hemodynamics on gastric mucosal blood flow in patients with liver cirrhosis. AB - The dependence of the gastric mucosal change in liver cirrhosis on the extrahepatic collaterals is still unknown. Therefore we studied the influence of these collateral hemodynamics on gastric mucosal blood flow and gastric mucosal lesions. The subjects were 23 cirrhotic patients and were divided into two groups by the findings of percutaneous transhepatic portography. The first group consisted of 14 cases whose extrahepatic collaterals were via esophageal varices (group I). The second group included 9 cases having collaterals other than esophageal varices (group II). Multiple red spots were observed in 13 of 14 cases in group I, and two of nine cases in group II. Gastric mucosal blood flow was 2.0 +/- 0.9 volts (mean +/- SD) in group I, 4.0 +/- 1.2 in group II. A statistically significant difference was observed between groups I and II. Gastric mucosal blood flow was not significantly correlated with portal venous pressure in group I. It is concluded that, in liver cirrhosis, gastric mucosal blood flow is changeable according to the types of the extrahepatic collaterals. PMID- 1505282 TI - Nitric oxide-mediated gastric hyperemia decreases ethanol-induced gastric mucosal injury in uremic rats. AB - We investigated whether the recently described endothelium-derived nitric oxide mediated gastric hyperemia in the uremic rat protects the gastric mucosa against ethanol injury. Uremia was induced by subtotal nephrectomy. Basal gastric mucosal blood flow, measured by a hydrogen gas clearance technique, was significantly higher in uremic than control rats. Continuous intragastric perfusion with 40% ethanol produced significantly less gross and histological lesions in uremic than in control rats. The administration of 3 mg/kg of NW-nitro-L-arginine methyl ester, a specific inhibitor of nitric oxide biosynthesis, decreased resting gastric mucosal blood flow to control levels in uremic rats, but had no effect on basal gastric blood flow in control rats. This pretreatment with the inhibitor of nitric oxide biosynthesis increased 40% ethanol-induced gastric mucosal lesions in uremic rats to the same level as that observed in control rats, but had no effect on lesions in control rats. In conclusion, this study suggests that in the uremic rat, gastric hyperemia, mediated by increased endothelium-derived nitric oxide, attenuates ethanol-induced gastric mucosal injury. PMID- 1505283 TI - Superior mesenteric artery is more important than inferior mesenteric artery in maintaining colonic mucosal perfusion and integrity in rats. AB - Mucosal hemodynamics (by reflectance spectrophotometry) and mucosal damage (by histologic examination) following acute colonic ischemia were evaluated in different anatomic locations in the colon of anesthetized rats. The reflectance spectrophotometer provides an index of mucosal hemoglobin concentration (IHB) and an index of oxygen saturation of hemoglobin (ISO2). The patterns of ischemia without congestion (decreases IHB, decreases ISO2) during superior mesenteric artery occlusion, and ischemia with congestion (increases IHB, decreases ISO2) during portal vein occlusion, previously demonstrated in the stomach and duodenum, are also applicable to the colon. The significant linear correlations between changes (as percent of baseline) in IHB, ISO2, and hydrogen gas clearance suggest that changes in these indices are adequate indicators of changes in colonic mucosal perfusion. Superior mesenteric artery ligation produced significant reductions in both indices, and an increase in damage in the mucosa of the cecum, transverse colon, splenic flexure, and left colon, but not the rectum. Inferior mesenteric artery ligation produced only slight reduction in these indices and minimal damage only in the mucosa of the splenic flexure. These results support the hypothesis that the superior mesenteric artery is more important than the inferior mesenteric artery in maintaining colonic perfusion and colonic mucosal integrity in the rat. PMID- 1505284 TI - Role of capsaicin-sensitive afferent neurons in mucosal blood flow response of rat stomach induced by mild irritants. AB - The role of capsaicin-sensitive sensory nerves in gastric mucosal blood flow (GMBF) responses to mild irritants was investigated in the rat stomach mounted on a lucite chamber using hypertonic NaCl and 0.2 N HCl. Exposure of the mucosa to hypertonic NaCl (0.5, 0.75, 1 M) for 10 min caused a reduction in the transmucosal potential difference (PD) in a concentration-related manner, followed by an increase of luminal pH and GMBF. In contrast, mucosal application of 0.2 N HCl caused no or little change in PD and pH, but increased GMBF significantly. Functional ablation of capsaicin-sensitive sensory nerves significantly inhibited the increase of GMBF after exposure to these irritants, although the PD and pH responses induced by 1 M NaCl remained unaltered by this treatment. Pretreatment with indomethacin (5 mg/kg, subcutaneously) significantly attenuated the GMBF responses to 1 M NaCl and 0.2 N HCl and inhibited the increase of pH caused by 1 M NaCl. Mucosal application of capsaicin (0.1 mg/ml for 10 min) produced an increase of GMBF without being accompanied by change in PD and pH, and this effect was significantly blocked by either indomethacin or chemical deafferentation. These results suggest that capsaicin-sensitive sensory nerves as well as endogenous prostaglandins may be involved in the mechanism of GMBF responses induced by mild irritants, and the latter might sensitize these nerves to mucosal irritation. PD reduction may be obligatory for pH but not GMBF responses. PMID- 1505285 TI - Sequence of gastric mucosal injury following ischemia and reperfusion. Role of reactive oxygen metabolites. AB - The mechanisms of gastric mucosal injury following a period of ischemia remain unclear. The aim of this study was to determine the relative contributions of ischemia, reperfusion, and reactive oxygen metabolites to mucosal injury induced by temporary occlusion of the celiac artery. Rats were subjected to 30 min of gastric ischemia in the presence of 100 mM HCl. Reperfusion periods ranged from 1 min to 24 hr. Drug treatments included allopurinol (100 mg/kg) or a combination of superoxide dismutase (15,000 units/kg), catalase (90,000 units/kg), and desferrioxamine (50 mg/kg). Mucosal injury was assessed by quantitative histology and the extent of macroscopic hemorrhage. Approximately one third of the total injury to the volume of the mucosa (11.8 +/- 9.1%) was due to ischemia alone. Another third was blocked by allopurinol or superoxide dismutase, catalase, and desferrioxamine (22.1 +/- 6.9%, P less than 0.001; and 25.9 +/- 4.6%, P less than 0.01), respectively, compared with control (32.5 +/- 5.1%). In contrast, extensive surface mucosal injury (62.2 +/- 27.6%) occurred primarily during ischemia and was not affected by antioxidants. Macroscopic hemorrhage was halved by treatment with allopurinol (17.5 +/- 12.6%, P less than 0.01) or superoxide dismutase, catalase, and desferrioxamine (15.9 +/- 14.5%, P less than 0.01). We conclude that temporary celiac occlusion results in gastric mucosal damage that consists of both ischemic and reperfusion components. The majority of surface mucosal injury occurred during ischemia, whereas injury to the volume of the mucosa and the vasculature occurred equally during reperfusion and was associated with reactive oxygen metabolites. PMID- 1505286 TI - Intestinal fatty acid-binding protein as a sensitive marker of intestinal ischemia. AB - Determination of the serum level of intestinal fatty acid-binding protein has been used to detect rat intestinal ischemia following ligation or 30-min occlusion of the superior mesenteric artery. The normal values were under the minimal detectable level of less than 2 ng/ml in all the 10 rats. The serum fatty acid-binding protein level increased rapidly, to 340.7 +/- 54.6, 438.5 +/- 40.1, 388.1 +/- 37.4, and 292.2 +/- 95.7 ng/ml (P less than 0.01) at 1, 2, 4, and 8 hr after ligation, respectively. It also increased, to 347.2 +/- 127.7 ng/ml (P less than 0.01) at 1 hr, after a 30-min transient occlusion and then returned to a normal level. Histological studies showed destruction of the villi, disappearance of the mucosa, and transmural necrosis with the progress of time after ligation, while no remarkable morphological change was observed following 30-min transient occlusion. These observations strongly suggest that the intestinal fatty acid binding protein is a useful biochemical marker for intestinal ischemia, particularly in the early reversible phase. PMID- 1505288 TI - Omeprazole heals mucosal ulcers associated with endoscopic injection sclerotherapy. AB - Endoscopic injection sclerotherapy (EIS) is a standard and definitive therapy for bleeding esophageal varices. While the overall complication rate of the procedure is low, a substantial minority of patients treated by EIS develop refractory mucosal ulceration and/or esophageal strictures. However, despite the prophylactic use of H2 blockers and sucralfate in our EIS protocol, we observed a number of patients who developed nonhealing esophageal and/or gastroduodenal ulceration. We conducted an open trial in which we enrolled nine patients who had refractory ulcer disease. Patients that enrolled in the trial exhibited complete healing of their mucosal ulcers. These results suggest that acid is an important contributory factor in the pathogenesis and perpetuation of EIS-associated mucosal ulceration. Patients with alcohol-associated liver disease may be at increased risk for the development of EIS-associated complications. PMID- 1505287 TI - Mealtime versus nighttime acid inhibition. A clinical pharmacological study with ranitidine. AB - This study was carried out in order to compare the effects of mealtime and bedtime regimens of ranitidine on gastric acidity. Fifteen duodenal ulcer patients in clinical remission were randomized to receive in single-blind fashion either placebo, ranitidine 300 mg at night (2200 hr) or ranitidine 150 mg three times a day given before each of the three daily meals (1800, 0800 and 1200 hr). Over 24 hr, the two active treatments produced a significantly greater acid inhibition than placebo, while the single daily regimen was superior to the three times a day regimen of ranitidine in terms of both rise in pH values (P less than 0.001) and duration of action expressed as time spent above 3.0 pH units (P less than 0.05). The analysis of these two parameters during fractioned periods of the circadian cycle showed that the three divided doses of ranitidine were more effective during the daytime (P less than 0.01) and the evening (P less than 0.001), whereas the bedtime dose of ranitidine was superior during the night (P less than 0.0001). Thus a short-lasting antisecretory action, which is, however, capable of fully controlling the high acidity of postprandial periods, might be the key to understanding the results of several recent clinical trials in which the suppression of daytime gastric acidity has been shown to promote similar or even faster duodenal ulcer healing rates than the suppression of nocturnal acidity. PMID- 1505289 TI - Effect of oral contraceptive use on reoperation following surgery for Crohn's disease. AB - The influence of oral contraceptive (OCP) use as a risk factor for the development of Crohn's disease is disputed. We wished to determine if OCP use affected the risk of recurrence (defined as need for a second surgery) in women who had already undergone a resection for Crohn's disease. We hypothesized that if contraceptive use was a risk factor for disease development, it could influence recurrence. Using a mail questionnaire, we surveyed 138 women regarding their OCP use following surgery for Crohn's disease. All participants were between ages 16 and 35 at the time of their initial surgery which occurred between 1966 and 1984. Ninety-seven women (70%) responded. Mean follow-up was 9.9 years (range 4-27). Forty-six women required a second surgery. The recurrence rate as determined by actuarial analysis, was 27.2% (95% confidence intervals (CI95 16.5-38.1) and 58.0% (CI95 37.8-78.2) at 5 and 10 years, respectively. Thirty-two women took OCP in the first year following surgery. Eleven OCP users (34.4%) required additional surgery compared to 34 (53.1%) of nonusers. Using life table analysis, the percentage requiring a second surgery was 25.0% (CI95 6.9-43.1) and 40.7% (CI95 1.5-80%) at 5 and 10 years, respectively, for users compared to 28.4% (CI95 6.9-43.1) and 64.0% (CI95 40.5-87.5) for nonusers (Lee Desu, P greater than 0.05). When surveyed about their reasons for using OCP, most women stated that their disease did not affect their decision to use contraceptives.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1505290 TI - Prooxidant properties of 5-aminosalicylic acid. Possible mechanism for its adverse side effects. AB - There is a growing body of experimental and clinical evidence to suggest that oral or rectal administration of 5-ASA or 5-ASA conjugates is associated with significant adverse side effects including pancreatitis, hepatitis, and renal toxicity. The objective of this study was to assess the ability of 5-ASA to interact with low-molecular-weight iron to yield oxygen-derived free radicals and to determine whether these oxidants could damage model biological compounds. We found that 5-ASA was very effective at chelating ferric iron (Fe3+), and it rapidly reduced Fe3+ to the ferrous form (Fe2+). Addition of the 5-ASA/Fe2+ chelate to solutions containing polyunsaturated fatty acids or deoxyribose resulted in lipid peroxidation and oxidative carbohydrate degradation, respectively. These results are consistent with the formation of the highly reactive (and cytotoxic) hydroxyl radical. Formation of this free radical species was confirmed by the ability of hydroxyl radical scavengers (dimethyl sulfoxide, dimethyl thiourea) to inhibit the 5-ASA/Fe-mediated oxidative reactions. Maximum hydroxyl radical formation was achieved at a 5-ASA-to-Fe3+ ratio of 1.0 (20 microM 5-ASA and 20 microM Fe3+). Increasing this ratio significantly inhibited OH. formation with a concomitant reduction in lipid peroxidation and deoxyribose degradation. Finally, we demonstrated that 5-ASA promotes the reductive release of Fe3+ from ferritin. Data obtained in this study suggest that 5-ASA may, under certain conditions, promote the formation of potentially injurious free radical species. These oxidative reactions may contribute to some of the adverse side effects known to be associated with the newer preparations of 5-ASA. PMID- 1505291 TI - Low bone mineral density in patients with inflammatory bowel disease. AB - To assess the prevalence and risk factors for low bone mineral density in inflammatory bowel disease, we studied 61 consecutive patients, mean age 36 +/- 11 years. Twenty-seven had a Crohn's disease and 34 ulcerative colitis (including 13 with ileoanal anastomosis). Three patients, two women and one man (32, 70, and 45 years old, respectively) had vertebral crush fractures. Bone mineral density measured by dual energy x-ray absorptiometry at spine and femoral level was more than 2 SD below normal values in 23% of the patients, all of them having received steroid therapy. Eighteen patients (29%) had never received steroid therapy; their bone mineral density was not different than those who had. Univariate analysis showed a positive correlation between bone mineral density and body weight or oral calcium intakes, and a negative correlation with steroid daily dose. After ileoanal anastomosis, bone mineral density was not different from other groups and showed a positive correlation with time elapsed since coloproctectomy. We concluded that bone mineral density is low in patients with inflammatory bowel disease and exposes them to the risk of bone fracture. Bone mineral density after ileoanal anastomosis may increase with time after surgery. PMID- 1505292 TI - Influence of shock on development of infection during acute pancreatitis in the rat. AB - This study tested the hypothesis that hypovolemic shock elicits or promotes the development of infection during acute pancreatitis. Pancreatitis was induced in rats by ligation of the common biliopancreatic duct; nonlaparotomized animals served as controls. After 24 hr, the animals were subjected to either sham-shock (instrumented only) or to shock by withdrawal of blood through a femoral artery line by maintaining the mean arterial blood pressure at 30 mm Hg for 1 or 2 hr. After completion of the shock period, the shed blood was returned to the animal. All animals were sacrificed 24 hr later and specimens obtained from portal and systemic blood, liver, spleen, pancreas, and mesenteric lymph nodes for bacteriologic culture using standard techniques. The pancreas was also analyzed by morphometric techniques. The histologic changes of pancreatitis induced by biliopancreatic obstruction were characterized by marked edema with accompanying mild inflammation, hemorrhage, and necrosis. Concomitant with these morphologic findings was an associated translocation of enteric organisms to the mesenteric lymph nodes without spread to distant organs. Shock by itself induced only a mild edema in the pancreas and did not cause bacterial translocation. Furthermore, shock failed to aggravate the morphologic alterations of acute pancreatitis and did not promote bacterial spread to mesenteric nodes over that observed with pancreatitis alone. Thus, we conclude that periods of severe shock lasting up to 2 hr do not play a major role in the pathogenesis of infection in our model of pancreatitis. PMID- 1505293 TI - Use of famotidine in severe exocrine pancreatic insufficiency with persistent maldigestion on enzymatic replacement therapy. A long-term study in cystic fibrosis. AB - In patients with pancreatic exocrine insufficiency, the use of pancreatic enzyme does not abolish steatorrhea in some cases. We carried out a long-term prospective study in an attempt to clarify the effectiveness of the associated use of famotidine to enzymatic supplementation on fat absorption and nutritional parameters of patients with pancreatic insufficiency due to cystic fibrosis. We studied 10 patients, mean age 12.5 years, with persistent steatorrhea on enzymatic supplementation. A double-blind crossover design was used and famotidine (1 mg/kg/day) or placebo was given as adjuvant to enzymatic preparations for either of two six-month periods. A statistically significative reduction in fecal wet weight (P less than 0.0001), an improvement in the coefficient of fat absorption (P less than 0.01) and in the steatocrit values (P less than 0.028) were found on famotidine. Moreover, the weight and the height increases were greater after famotidine than after placebo period (respectively, P less than 0.012 and P less than 0.01); also the serum calcium and triglycerides levels were higher after the period on famotidine (respectively, P less than 0.0025 and P less than 0.025). No adverse effects of famotidine were noted. These data suggest that famotidine is a useful adjuvant to pancreatic enzyme therapy in patients with severe pancreatic insufficiency and persistent maldigestion on large doses of pancreatic supplements; in fact, famotidine improves not only fat absorption but the nutritional status of the patients. PMID- 1505294 TI - Acute pancreatitis in Behcet's disease. PMID- 1505295 TI - Phlegmonous gastritis associated with HIV-1 seroconversion. Endoscopic and microscopic evolution. AB - A 40-year-old man presented with peritonitis. Diagnosis of phlegmonous gastritis was made by laparotomy. Conservative treatment combined with antibiotics was successful. Multiple endoscopies with biopsies illustrate the natural history of this disease. The patient developed HIV-1 seroconversion during hospital stay. Prompt diagnosis and treatment may improve the prognosis of this often lethal disease. PMID- 1505296 TI - Primary intrahepatic cholesterol stones. Report of one case and treatment with ursodeoxycholic acid. PMID- 1505297 TI - Antibiotic-associated colitis and cystic fibrosis. AB - The use of antibiotics in patients with cystic fibrosis is widespread, and fecal carriage of Clostridium difficile occurs in up to 50% of these patients; however, antibiotic-associated colitis appears to be a rare occurrence. The reasons why this is so remain unknown. A case of antibiotic-associated colitis occurring in a patient with cystic fibrosis is described. Possible mechanisms for the rarity of antibiotic-associated colitis are reviewed and implications for prompt diagnosis and therapy are discussed. PMID- 1505298 TI - There are no formulae for determining how large a sample is needed in multiple regression or any multivariate technique. PMID- 1505299 TI - Prevalence of esophagitis. PMID- 1505300 TI - High systolic blood pressure increases prevalence and severity of retinopathy in NIDDM patients. AB - OBJECTIVE: To determine whether the severity of retinopathy is higher in a group of NIDDM patients with sBP greater than or equal to 140 mmHg compared with NIDDM patients with sBP less than 140 mmHg. RESEARCH DESIGN AND METHODS: Ophthalmoscopy and FAG were conducted among a group of NIDDM patients with either a sBP above (n = 54) or below (n = 55) 140 mmHg. The groups were matched according to diabetes duration, metabolic control (HbA1c), and AER. RESULTS: Patients with sBP greater than 140 mmHg had a higher prevalence of retinopathy, as established according to a rating scale (4.9 +/- 3.8 vs. 3.2 +/- 3.3, P less than 0.02); furthermore, their BMI values were higher (28.1 +/- 4.5 vs. 24.9 +/- 4.1 kg/m2, P less than 0.001). The group of normotensive subjects showed the highest rate of low grading (0-2) values. However, the highest prevalence rates of 8-10 grading values (proliferative retinopathy) were found in the hypertensive group. CONCLUSIONS: These data suggest that sBP values greater than or equal to 140 mmHg favor the onset of retinopathy in NIDDM patients during their 1st 10 yr of disease. PMID- 1505301 TI - Homogeneity in pattern of decline of beta-cell function in IDDM. Prospective study of 204 consecutive cases followed for 7.4 yr. AB - OBJECTIVE: To study the natural history of beta-cell function from onset of IDDM to expected deterioration of insulin (C-peptide) secretion and to identify different patterns of decline, if any. RESEARCH DESIGN AND METHODS: A cohort of 204 consecutive newly diagnosed IDDM (clinical criteria) patients were followed prospectively for 7.4 yr (range 6-9 yr), measuring fasting C-peptide at onset, 1, 3, 6, 9, 12, and then every 6 mo until 106 wk (range 104-135 wk). Then, postprandial C-peptide was measured. RESULTS: Fasting C-peptide was 0.17 nM (range 0.11-0.25 nM) at onset followed by an annual increase rate of 0.16 nM/yr (range 0.06-0.48 nM/yr) to a peak of 0.28 nM (range 0.23-0.34 nM/yr) after 25 wk (range 12-39 wk). The subsequent annual decline rate of fasting C-peptide was 0.08 (0.05-0.12) and of postprandial C-peptide 0.03 nM/yr (range 0.02-0.06 nM/yr). None of these parameters showed bimodality in their distribution. However, some parameters were important. In men, fasting C-peptide at onset was lower, but the initial C-peptide increase rate was more pronounced compared to women. Furthermore, insulin-free remission was related to higher C-peptide levels throughout the study. C-peptide was higher during the 1st yr of diabetes in subjects greater than 30 yr of age at onset compared with younger diabetic patients. Stepwise multiple regression analysis showed that age, male sex, and fasting C-peptide at onset were of some predictive value for the C-peptide levels at 5 yr. However, simple group comparisons revealed no significant differences. CONCLUSIONS: No major heterogeneity exists in the pattern of decline of beta-cell function in IDDM, although small differences in pattern could be identified in both sexes, in different age-groups, and in relation to achieving insulin-free remission. PMID- 1505303 TI - Asymptomatic hyperglycemia and atherosclerotic vascular disease in the elderly. AB - OBJECTIVE--To investigate the relationship between asymptomatic hyperglycemia (IGT or newly diagnosed NIDDM) and atherosclerotic vascular disease. RESEARCH DESIGN AND METHODS--A representative cross-sectional population sample of 1431 subjects (511 men, 920 women; 65-74 yr old). Altogether, 312 men and 515 women had NGT, 84 men and 158 women had IGT, 33 men and 59 women had newly diagnosed NIDDM, and 82 men and 188 women had previously diagnosed NIDDM. Participation rate was 71%. Main outcome measures were prevalence rates of CHD, stroke, and intermittent claudication. RESULTS--There was no difference in the prevalence of definite or possible MI verified at hospital between subjects with asymptomatic hyperglycemia and NGT (15.5 vs. 13.3% in men, 6.3 vs. 5.3% in women). Men with asymptomatic hyperglycemia had 1.5 x higher prevalence of angina pectoris (29.4 vs. 19.3%, P less than 0.05), major Q-QS changes (21.1 vs. 12.0%, P less than 0.05), ischemic ECG changes (59 vs. 45%, P less than 0.05), and silent MI on ECG (14.8 vs. 7.9%, P less than 0.05) compared to men with NGT. Women with asymptomatic hyperglycemia had more often ischemic ECG changes compared to women with NGT (48.3 vs. 39.7%, P less than 0.05). There was no difference (NS) in the prevalence of verified stroke (3.5 vs. 4.6% in men, 2.7 vs. 2.5% in women) or claudication (7.0 vs. 7.7% in men, 4.6 vs. 4.3% in women) between subjects with asymptomatic hyperglycemia and NGT. In multiple logistic regression analyses, the association between risk factors and MI or ischemic ECG changes in subjects with asymptomatic hyperglycemia was not consistent. CONCLUSION--Elderly subjects with asymptomatic hyperglycemia (particularly men) tended to have an increased prevalence of CHD. Thus, asymptomatic hyperglycemia in the elderly is not a benign phenomenon but is associated with cardiovascular morbidity. PMID- 1505302 TI - Granulocytes and three-phase bone scintigraphy for differentiation of diabetic gangrene with and without osteomyelitis. AB - OBJECTIVE: In diabetic gangrene, concomitant osteopathy and soft-tissue infection often render laboratory and roentgenographic signs unreliable as indicators of osteomyelitis. In this situation, scintigraphic methods can be helpful. RESEARCH DESIGN AND METHODS: Relying on the long-term clinical course as the final indicator of presence or absence of osteomyelitis, we prospectively compared in 31 patients three-phase bone scintigraphy with either indium-labeled autologous granulocytes (n = 20) or 123I-labeled antibodies against granulocytes (n = 11). RESULTS: Three-phase bone scintigraphy and imaging with indium-labeled autologous granulocytes yielded sensitivities and specificities of 95 and 70% for bone scintigraphy and 77 and 100% for granulocyte scintigraphy, respectively. One patient with severe angiopathy and proved osteomyelitis had a negative bone scintigraphy but a positive scintigraphy with labeled antibodies against granulocytes. One patient with aseptic bone necrosis presented with a formally false positive result with both methods. CONCLUSIONS: In contrast to former retrospective studies, three-phase bone scintigraphy compares very well with granulocyte scintigraphy. The care of most patients can be managed with clinical data and this widely available scintigraphic method. PMID- 1505305 TI - Severe hypoglycemia incidence and predisposing factors in 85 pregnancies of type I diabetic women. AB - OBJECTIVE: To evaluate the incidence and predisposing factors of severe hypoglycemia (SH) in pregnant women with insulin-dependent (type I) diabetes mellitus. RESEARCH DESIGN AND METHODS: SH (impairment of consciousness due to hypoglycemia subsequently treated with glucagon or i.v. glucose) was recorded in all pregnant type I diabetic women (n = 77) who attended our pregnancy clinic during 85 pregnancies from 1986 to 1990. RESULTS: Ninety-four SHs were reported during 35 pregnancies. Of 94 SHs, 84% occurred before the 20th gestational wk (median 12th wk) and 77% during sleep. In the group with SH, there was no permanent maternal sequelae, and there was a favorable fetal outcome (no perinatal death and no congenital malformation). Mean HbA1c values were not different between the group with and without SH for the first half (6.4 +/- 1.1 vs. 6.3 +/- 0.9%) and 2nd half (5.4 +/- 0.6 vs. 5.5 +/- 0.7%) of pregnancy. The percentage of women with SH before pregnancy (51 vs. 28%, P less than 0.05) and the incidence of SH patients before pregnancy (0.49 vs. 0.08 SH/patient/yr) was different between the group with and without SH. CONCLUSIONS: SH is frequent during pregnancies of type I diabetic women with near normoglycemia. The risk for SH is particularly pronounced during the first half of pregnancy and in women with a history of SH. PMID- 1505304 TI - Twice-daily humulin ultralente insulin decreases morning fasting hyperglycemia. AB - OBJECTIVE: To test whether a two-injection regimen of HUL/R would improve FBG and metabolic control in pediatric IDDM patients with a dawn rise in FBG compared with our standard twice-daily therapy, HL/R. RESEARCH DESIGN AND METHODS: Seventy seven patients with fasting hyperglycemia (prebreakfast mean FBG greater than or equal to 8.3 mM (150 mg/dl) during the preceding 2 wk) were evaluated with twice weekly midsleep (0230-0330) FBG for 2 wk. Forty-seven patients (61%) had a mean dawn rise between midsleep and prebreakfast of greater than or equal to 2.8 mM (50 mg/dl). Patients continued on HL/R for an additional 4 wk, after which 31 patients were then randomized into a double-blind 12-wk trial of either HUL/R (n = 14) or HL/R (n = 17) administered before breakfast and the evening meal. Midsleep FBG was obtained twice weekly with weekly insulin adjustment as needed to optimize glycemic control. FBG was monitored and verified with memory glucometers (Glucometer M). HbA1c levels were measured at the time of physician visits at 0, 6, and 12 wk. RESULTS: Prebreakfast FBG was lower in the HUL/R treated patients (10.6 +/- 0.6 vs. 12.6 +/- 0.6 mM [191 +/- 6.4 vs. 227 +/- 11.2 mg/dl], P less than 0.02). The dawn rise was diminished in the HUL/R patients (0.5 +/- 0.5 vs. 2.6 +/- 0.7 mM [9 +/- 8.3 vs. 46 +/- 11.7 mg/dl], P less than 0.02). FBG at lunch, dinner, bedtime, and midsleep were similar in both groups, and HbA1c did not differ between groups or change significantly in either group during the 12-wk trial. Insulin dose, percentage R, day-night dosage split, and episodes of hypoglycemia (FBG less than 3.3 mM [60 mg/dl]) were similar in both groups. CONCLUSIONS: A 12-wk trial of twice-daily HUL/R improved fasting glycemia in pediatric patients with a dawn rise but did not improve metabolic control as measured by HbA1c. PMID- 1505306 TI - Plasma endothelinlike immunoreactivity levels in IDDM patients with microalbuminuria. AB - OBJECTIVE: To determine whether plasma endothelin, a potent vasoconstrictor and growth factor for vascular smooth muscle, is elevated in microalbuminuric insulin dependent diabetes mellitus patients. RESEARCH DESIGN AND METHODS: Plasma endothelinlike immunoreactivity was measured by radioimmunoassay in 15 microalbuminuric diabetic patients, 12 normoalbuminuric diabetic patients, and 12 control subjects. RESULTS: The mean levels of plasma endothelinlike immunoreactivity were raised in the normoalbuminuric patients (8.4 pM [range 4.8 12.7 pM]; P less than 0.01) and the microalbuminuric patients (10.2 pM [range 5.6 31.1 pM]; P less than 0.001) compared with control subjects (6.1 pM [range 4.5 7.6 pM]). Plasma endothelinlike immunoreactivity was also higher in the microalbuminuric patients compared with the normoalbuminuric patients (P less than 0.05). CONCLUSIONS: The increase in plasma endothelinlike immunoreactivity further confirms endothelial dysfunction in diabetes and this increase in plasma endothelin may contribute to the vascular disease prevalent in diabetes. PMID- 1505307 TI - Use of blood glucose data by families of children and adolescents with IDDM. AB - OBJECTIVE: Prospective evaluation of the use of blood glucose test results for treatment actions by families of youth with IDDM. RESEARCH DESIGN AND METHODS: Forty-seven patients with IDDM used reflectance meters with memory for SMBG for 28 days. Parents kept weekly diaries of six types of uses of SMBG data. We collected SMBG data from the reflectance meters, HbA1 and serum fructosamine assays, and measures of behavioral factors that could affect use of SMBG data. RESULTS: Families recorded a mean of 4.85 data-based actions during the 28-day study, and 74% of the families reported at least one such action. Fifty percent of recorded actions consisted of management of hypoglycemia and, among the remainder, only 18% were anticipatory, proactive actions. Partial correlation analysis showed that families with more frequent use of SMBG data had less parent child conflict about diabetes, more diabetes knowledge, and better overall treatment adherence. Use of SMBG data was unrelated to objective indices of the need for treatment adjustments or to diabetic control. CONCLUSIONS: Most families made active use of their SMBG data, but few of these actions were proactive. Behavioral factors were stronger predictors of family use of SMBG data than were objective indices of the need for treatment adjustments. The results illustrate the need for further research on use of SMBG data and methods to enhance its impact on diabetic control. PMID- 1505308 TI - Immediate HbA1c results. Performance of new HbA1c system in pediatric outpatient population. AB - OBJECTIVE: This study compared the performance of a new device that uses an IA to measure HbA1c in 9 min with a 1-microliter capillary blood sample with AC and CE methods in both nondiabetic and diabetic pediatric patients. RESEARCH DESIGN AND METHODS: Two hundred seven pediatric subjects (103 nondiabetic, 104 with insulin dependent diabetes mellitus) had HbA1c measured with the IA method and compared with total GHb values determined by AC and HbA1 by the CE method with the same whole-blood capillary aliquot. Glucose values were also obtained from the same blood samples. RESULTS: Correlations and regression analyses show excellent correspondence between the three assays. The correlation between the AC and CE methods is 0.98 (P less than 0.001) with a slope of 1.615 +/- 0.0125 and intercept of 4.00 +/- 0.20. The correlation between the IA and AC methods is 0.99 (P less than 0.001) with a slope of 0.608 +/- 0.007 and intercept of 1.326 +/- 0.066. The correlation between the IA and CE methods is 0.97 (P less than 0.001), with a slope of 0.983 +/- 0.018 and intercept of 1.122 +/- 0.153. The average difference and average percentage difference between methods were also significant (P less than 0.001), reflecting the differences in GHb components measured. There was a significant correlation (P less than 0.001) between each method and glucose values (IA r = 0.72, AC r = 0.70, CE r = 0.73). Within-run precision for IA ranged from 1.7 to 3.5% and between-run precision 2.7 to 4.1%. CONCLUSIONS: Study results suggest that the IA method gives extremely accurate and reliable values over the clinical range of interest. The instrument is small, portable, easy to use, and provides information within 9 min for both physicians and patients. PMID- 1505309 TI - Comparison of two commonly used standard IVGTTs. AB - OBJECTIVE: To compare the magnitude and reproducibility of the FPIR measured during two different IVGTT protocols in nondiabetic subjects. RESEARCH DESIGN AND METHODS: Nine control subjects each had two pairs of IVGTTs with either a 4-min infusion of 0.5 g/kg glucose or a 1-min infusion of 0.3 g/kg glucose. Blood glucose and serum insulin were measured before and 1, 2, 3, 5, and 10 min after completion of the glucose infusion. The FPIR was measured with either 1 + 3-, 2 + 3 + 5-, or 1 + 3 + 5-min serum insulins, areas under the insulin curve (0-5 or 0 10 min), or the ratio of serum insulin to blood glucose area. RESULTS: The FPIR was higher in eight of nine subjects with the short-infusion test, but the within subject variation of the two methods was identical. Reproducibility was not significantly improved with an integrated insulin area or insulin-to-glucose ratio measurement. CONCLUSIONS: Reproducibility of the FPIR measured during IVGTT is not significantly affected by the duration of the glucose infusion. However, the magnitude of the difference in FPIR observed between the two protocols highlights the need for standardization of the methodology if the IVGTT is to be used in studies of the preclinical stage of IDDM. PMID- 1505310 TI - Two incidents of alleged duplicate publication. PMID- 1505312 TI - Journals and authors: rules, principles, and ethos. PMID- 1505311 TI - Duplicate publication in American Diabetes Association journals: challenges and recommendations. Publications Policy Committee, American Diabetes Association. PMID- 1505313 TI - Magnesium supplementation in the treatment of diabetes. American Diabetes Association. PMID- 1505314 TI - New oral thiazolidinedione antidiabetic agents act as insulin sensitizers. PMID- 1505315 TI - Proceedings of a consensus development conference on standardized measures in diabetic neuropathy. Clinical measures. PMID- 1505317 TI - Proceedings of a consensus development conference on standardized measures in diabetic neuropathy. Electrodiagnostic measures. PMID- 1505316 TI - Proceedings of a consensus development conference on standardized measures in diabetic neuropathy. Morphological and biochemical measures. PMID- 1505318 TI - Proceedings of a consensus development conference on standardized measures in diabetic neuropathy. Quantitative sensory testing. PMID- 1505319 TI - Proceedings of a consensus development conference on standardized measures in diabetic neuropathy. Autonomic nervous system testing. PMID- 1505320 TI - Proceedings of a consensus development conference on standardized measures in diabetic neuropathy. Summary and recommendations. PMID- 1505321 TI - Glucokinase gene mutation linked to early-onset NIDDM. PMID- 1505322 TI - Endless debate about an unsubstantiated cause of severe hypoglycemia: reply to human versus porcine insulin gone wrong. PMID- 1505323 TI - Methodology concerns in study of hypoglycemia potential under human versus animal insulin treatment. PMID- 1505324 TI - Insulin storage and injection recommendation. PMID- 1505325 TI - Study in Tanzania of IGT. Effect of regression to the mean. PMID- 1505326 TI - Fruit juices and gestational diabetes. PMID- 1505327 TI - Smokers with IDDM experience excess morbidity. The Colorado IDDM Registry. AB - OBJECTIVE--To determine whether there is an association between smoking and the self-reported morbidity of people with IDDM and to evaluate the nature of a possible interaction between smoking and IDDM in increasing the risk of morbidity among smokers with IDDM. RESEARCH DESIGN AND METHODS--Subjects were non-Hispanic whites aged 18-28 yr who participated in the Colorado IDDM Registry Follow-up Survey (case subjects, n = 24) or the 1985 NHIS (control subjects, n = 5876). Assessments of self-reported morbidity included any hospitalization in the past year; bed days, sick days, and limited-activity days in the past 2 wk; and ratings of poor health. The criteria outlined by Saracci were used to determine whether smoking was associated with greater morbidity among IDDM case compared to control subjects (smoking by IDDM interaction). RESULTS--Age- and sex-adjusted ORs, estimated from logistic regression, showed that people with IDDM reported excess morbidity compared with control subjects, regardless of smoking status. Smokers with IDDM reported morbidity 3-10 times as often as nonsmoking control subjects and were 2-3 times more likely to report morbidity than nonsmokers with IDDM. The smoking by IDDM interaction was more than multiplicative for all morbidity measures. Fifty to 75% of excess morbidity in young smokers with IDDM over simple additive effects was related to the interaction between smoking and IDDM. CONCLUSIONS--There was excess reported morbidity among people with IDDM who smoked, greater than that expected from the combined effects of smoking and IDDM. Smoking cessation in young people with IDDM may alleviate some of this excess, but more study is needed to determine whether smoking serves as an indicator of poor IDDM care practices or has a physiological impact that compounds the morbidity experienced by people with IDDM. PMID- 1505328 TI - Diabetic ketoacidosis. A rare complication of gestational diabetes. AB - OBJECTIVE: To describe a case of severe DKA in an otherwise healthy pregnant woman. RESEARCH DESIGN AND METHODS: We describe 2.5 yr of close follow-up of a Bedouin woman who was hospitalized for DKA while pregnant with her 11th child. Plasma glucose returned to normal levels immediately after delivery of a dead conceptus. Four months later, while normoglycemic, the patient became pregnant again. During the subsequent pregnancy, GDM was diagnosed at week 20 of gestation. Tight plasma glucose control was achieved with an insulin regimen, and the patient delivered a healthy girl at term. Plasma glucose again returned to normal and remained so to date, 18 mo postpartum. An OGTT and a euglycemic hyperinsulinemic clamp were performed between pregnancies; another OGTT was performed at week 14 of the last pregnancy. Plasma glucose, insulin, and C peptide were measured in blood samples during these procedures. RESULTS: We established beyond doubt that the patient developed GDM and returned to essentially normal glucose tolerance after her last (12th) delivery. During the 11th pregnancy, gestational diabetes was complicated by severe DKA. CONCLUSIONS: GDM is a common abnormality of glucose metabolism during pregnancy, which affects fetal development and leads to peripartum complications. Our report stresses that under certain circumstances, gestational diabetes can be complicated by DKA and become life-threatening to the mother and fetus. PMID- 1505329 TI - Telephone modem access improves diabetes control in those with insulin-requiring diabetes. AB - OBJECTIVE: To assess whether modem access improves diabetes control in IDDM patients. RESEARCH DESIGN AND METHODS: Forty-two patients participated in the study and were followed for 12 wk. The patients were randomly divided into two groups at baseline, a modem group and a control group. There were no significant differences between HbA1c, random blood glucose, and weight between the groups at the beginning of the study. Patients were asked to perform five blood glucose determinations/day (before breakfast, before lunch, afternoon [1500], before dinner, and at bedtime) twice/week. The modem group transferred their data over the phone once/week. The control group would bring in their results on their regular visits every 6 wk. Patients in the modem group were counseled every week over the telephone after transferring results to adjust insulin and food intake if necessary. RESULTS: In the modem group, HbA1c improved from 0.106 to 0.092 (13.20%). The control group improved from 0.112 to 0.102 (8.9%). There was no significant change in weight, random blood glucose, or insulin. CONCLUSIONS: The use of telephone modem-based patient-monitoring systems in diabetes clinical research seems to stimulate the patient to keep closer control of blood glucose levels. It might be especially useful in rural settings, for which this study was designed. PMID- 1505330 TI - Glycemic control in early IDDM. The Wisconsin Diabetes Registry. AB - OBJECTIVE: A cohort (n = 277) was followed from diabetes diagnosis to evaluate longitudinal glycemic control, urinary C-peptide levels, and certain features of diabetes self-management. RESEARCH DESIGN AND METHODS: Unselected cases with IDDM, who were less than 30 yr of age, were identified at diagnosis from a 28 county area in Wisconsin. Subjects were asked to submit blood every 4 mo for GHb testing, to report aspects of diabetes self-management every 6 mo, and to collect a 24-h urine specimen 4 mo after diagnosis. RESULTS: In the 1st yr of diabetes, the rate of increase (0.23%/mo) in GHb was significant for the cohort (P less than 0.001) and for almost all age and sex subgroups. In the 2nd yr, there was no significant rate of increase for the cohort as a whole (P greater than 0.10). Adolescent males (10-19 yr of age) had a mean GHb level for year 2 higher than males of other age-groups and higher than female adolescents (P less than 0.001). Adolescent males had a significant rate of increase in GHb for year 2 (P = 0.02), unlike all other age and sex subgroups. Adolescents had higher initial 24-h urine C-peptide levels than children less than 10 yr of age (P less than 0.01). During the 2nd yr of diabetes, the percentage of adolescent males reporting three or more insulin injections/day was lower than any other subgroup. CONCLUSIONS: These data-suggest that glycemic control stabilizes during the 2nd yr of IDDM, except in adolescent males, and that this may be due partly to aspects of self management. PMID- 1505331 TI - Assessment of glucose tolerance test criteria for diagnosis of diabetes in Chinese subjects. AB - OBJECTIVE: To examine and compare WHO diagnostic criteria for diabetes mellitus. RESEARCH DESIGN AND METHOD: The relationship between FPG and 2-h glucose are examined in 680 OGTTs with a quadratic regression model and ROC analysis. Simultaneous measurements of HbA1 and fructosamine are also compared with multiple linear regression. RESULTS: Two hundred eighteen subjects (32%) had 2-h glucose greater than or equal to 11.1 mM, of which only 86 had FPG greater than or equal to 7.8 mM. Only 2 subjects had FPG greater than 7.8 mM and 2-h glucose less than 7.8 mM. Of subjects with 2-h glucose less than 7.8 mM (n = 332), only 9 had FPG greater than 6.0 mM. From the quadratic model, the predicted FPG corresponding to 2-h glucose = 11.1 mM was 5.7 mM, whereas the predicted 2-h glucose corresponding to FPG = 7.8 mM was 15.2 mM. ROC analysis showed that, with 2-h glucose greater than or equal to 11.1 mM as indicating diabetes, an FPG of 5.6 mM gave an intersect for sensitivity and specificity of 87%. HbA1 and fructosamine correlated more closely with 2-h glucose and area under the OGTT curve than with FPG. CONCLUSIONS: Given that a 2-h glucose cutoff of 11.1 mM can be justified from other studies, our results suggest that the FPG cutoff of 7.8 mM when used for screening purposes should be reduced. At a suggested value of 7.0 mM, specificity remains 98.5%, whereas sensitivity increases to 57%. PMID- 1505332 TI - Fibrinolytic system during long-distance running in IDDM patients and in healthy subjects. AB - OBJECTIVE: Endurance exercise has been advocated in diabetes mellitus to improve both metabolic control and prevent atherosclerotic complications. The response of the fibrinolytic system during prolonged exercise has not been studied in diabetes. RESEARCH DESIGN AND METHODS: In seven male marathon runners with IDDM and eight healthy nondiabetic male control subjects, matched for age and degree of training, we studied fibrinolytic and coagulation parameters during a 3-h 32 km outdoor running session. Measurements included t-PA, u-PA, PAI-1, PAP (as a measure of in vivo activation of fibrinolysis), FbDPs, FGN, vWF, and VIII:C. RESULTS: In both IDDM and control subjects, levels of t-PA, u-PA, PAP, vWF, and VIII:C continued to rise throughout the exercise, whereas PAI-1 showed a similar decline in both groups. FbDP rose slightly in both groups, and FGN remained unchanged. t-PA levels during exercise correlated closely with exercise intensity. These findings indicate that continued stimulation by exercise does not deplete endothelial PA stores. Differences between IDDM and control subjects were seen only for t-PA, vWF, and u-PA. The AUC during exercise (AUC0.5-3.0) of t PA in IDDM was insignificantly lower than in control subjects (53 +/- 19 vs. 67 +/- 31 ng.ml-1.h), but the ratio of t-PA to exercise intensity was lower in IDDM (0.24 +/- 0.11 vs. 0.31 +/- 0.13, P less than 0.05). The AUC0.5-3.0 of vWF was lower in IDDM than in control subjects (569 +/- 268 vs. 880 +/- 265%.h, P less than 0.05). The AUC0.5-3.0 of u-PA was higher in IDDM than in control subjects (15.1 +/- 3.5 vs. 11.2 +/- 1.8 ng.ml-1.h, P less than 0.05). CONCLUSIONS: Despite a defect in the exercise-induced endothelial release of vWF and t-PA, the overall potential to activate fibrinolysis is intact in IDDM, possibly by enhancement of u-PA after exercise. Our data suggest that in IDDM, as in nondiabetic subjects, long-distance running may slow the progression of atherosclerosis by stimulating fibrinolysis. PMID- 1505333 TI - Factors predicting course of beta-cell function in IDDM. AB - OBJECTIVE: The purpose of this study was to determine whether the severity o clinical presentation, sex, age, HLA type, and the presence of IAs and ICAs could predict the variation of residual insulin secretion as measured by the serum C peptide response to a Sustacal meal. RESEARCH DESIGN AND METHODS: A cohort of 151 newly diagnosed IDDM children (mean age 10.2 +/- 4.6 yr) was followed prospectively for 3 yr. Thirty-five patients (12 males, 23 females) were still secreting C-peptide after 36 mo. RESULTS: We found that age (P = 0.0001), sex (P = 0.003), presence of ICA (P = 0.006), severity of clinical presentation (P = 0.001), and symptom duration (P = 0.002) significantly predicted the rate of loss of C-peptide secretion. The risks of accelerated C-peptide disappearance decreased with increasing age, the risk ratios being 0.25 for the older group (greater than 12 yr) compared with the younger group (less than 6 yr) and 0.50 for the intermediate group (6-12 yr) compared with the younger group. The risk for the presence of ICA was 1.7, and the risk for males was 1.7 also. There was a significant negative correlation between ICA titers and C-peptide at 18 and 24 mo after diagnosis (P = 0.04). There were no significant differences in HbA1 values between patients who secreted C-peptide and those who did not. CONCLUSIONS: We conclude that younger age of onset, male sex, high titers of ICA, severe clinical presentation, and shorter symptom duration significantly predict accelerated rates of loss of C-peptide secretion. PMID- 1505334 TI - Fundus pigmentation and the dark-adapted electroretinogram. AB - Dark-adapted electroretinograms were obtained over a 3.6-log range of stimulus intensities from 17 black and 15 white normal subjects. Subjects were grouped on the basis of light or dark fundus pigmentation, determined from digitized fundus photographs. B-wave amplitudes for each group were fitted by the Naka-Rushton equation, and the measures Vmax, log K, and n were determined. The luminance response functions revealed that subjects with light fundi had larger b-wave amplitudes at all luminance levels. There was a significant difference between groups for Vmax and n but not for log K. A comparison of b-wave implicit times showed no significant difference between subjects with dark and light fundi. Ancillary tests and multiple regression analysis suggested that the relationship between Vmax and fundus pigmentation could not be attributed to age, gender, refractive error, axial length or intraocular pressure. The results have implications for the collection of normative electroretinographic data and for the interpretation of electroretinogram results. PMID- 1505335 TI - Color electroretinography. A method for separation of dysfunctions of cones. AB - Electroretinograms to white and color stimuli were recorded in four normal subjects and nine subjects with different cone dysfunctions, including protanopia, cone dystrophy, cone dystrophy with supernormal b-waves at dark adaptation, cone dystrophy with missing b-waves during light adaptation and rod cone dystrophy with blue cone hypersensitivity. Color stimuli were obtained with Kodak Wratten filters in blue, blue-green, green, yellow and red. Electroretinograms to all stimuli were recorded during dark and light adaptation with different stimulus intensities and to 30-Hz flicker stimulation. In protanopia, responses to red during light adaptation and flicker stimulation were reduced. All cone dystrophies showed reduced amplitudes and prolonged implicit times to red when dark adapted. The light-adapted responses were equally reduced to all color stimuli in cone dystrophy and cone dystrophy with supernormal b waves. Contrary to other cone dystrophies, in cone dystrophy with missing b waves, responses to red were severely reduced and responses to green were preserved, indicating a predominantly red cone dysfunction. Blue cone hypersensitivity was clearly distinct from other dystrophies in having large response to blue and blue-green and much smaller responses to all other colors in all stimulus conditions. The electroretinogram with color stimuli allowed separation of different cone dysfunctions and identification of new retinal dysfunction syndromes. PMID- 1505336 TI - Spectral characteristics of rapid off-response in congenital deuteranomaly in one of monozygotic female twins. AB - The spectral sensitivity of the rapid off-response in the electroretinogram was studied in monozygotic female twins. One case was diagnosed as congenital deuteranomaly, and the other was normal. The log ratio of the sensitivity at 480 nm to the sensitivity at 620 nm (log S480/S620) was within the deutan range in the first case and within the normal range in the second. The two case were determined to be different at the retinal receptor level by study of the rapid off-response. This result of the rapid off-response was consistent with the results of the psychophysical examinations. PMID- 1505337 TI - Electrophysiologically determined contrast sensitivity in patients with ocular hypertension and chronic glaucoma. AB - Subjectively assessed contrast sensitivity has been found to be abnormal in many patients with glaucoma. We previously reported the use of onset-offset visual evoked potential measurements to determine contrast threshold objectively. We now studied 216 patients (79 with ocular hypertension and 137 with chronic simple glaucoma) with this technique. In comparison with an age-matched control group (68 subjects), mean contrast threshold was found to be significantly different in both patient groups, the degree of significance being greater in the patients with chronic simple glaucoma. Additionally, the slope of the CI-CII amplitude versus log contrast plot was shown to be depressed in the majority of affected eyes in patients with unilateral chronic simple glaucoma. This measure appears to give an indication of suprathreshold contrast processing and is related to the difference in luminance between pattern elements, rather than the quality of the border or "edge" between them. The data support not only an increase in contrast threshold (reduced sensitivity) in early glaucoma and some patients with ocular hypertension but also a suppression in suprathreshold function that is not readily measurable with standard psychophysical methods. The findings are consistent with recent theories concerning the effect of early chronic simple glaucoma on the function of Y-type units of the M (magnocellular)-type pathways. PMID- 1505338 TI - Cortical potentials to pattern reversal and luminance onset under ramp stimulation conditions in glaucoma. AB - Stimulus quantities with a ramp-like temporal course evoke cortical potentials that are delayed and attenuated in comparison with responses evoked by a step like course. This delay probably depends on temporal transfer characteristics of the activated precortical visual system. In a pilot study, luminance onset and pattern-reversal stimulation using this technique (light-emitting diode stimulator; transition time, 50 ms) were applied to 18 glaucomatous eyes with early visual field damage. The visual evoked cortical potential latency shifts between ramp and step mode were compared with visual field indices (mean defect, corrected loss variance). The pattern-reversal stimulation in ramp mode yielded a significant difference between the glaucoma group and normal subjects (p less than 0.004). The difference between groups with pattern-reversal stimulation in step mode was not significant (p = 0.15). From the determined visual field indices, only the mean defect showed a significant correlation to the measured visual evoked cortical potential latency shift, with both luminance-onset and pattern-reversal stimulation. In glaucoma with early malfunction, the precortical transmission and processing of lower and middle temporal frequencies, which are predominant in ramp-like temporal stimulus courses, are obviously more affected than the transmission of higher frequencies. The ramp stimulation technique for visual evoked cortical potentials might be of interest as a tool to detect early and specific functional defects in glaucoma. PMID- 1505339 TI - Pattern flash visual evoked potentials in patients with homonymous hemianopia. AB - Visual evoked potentials from seven horizontally spaced electrodes were recorded from normal subjects and subjects with homonymous hemianopia in response to hemifield pattern flash stimulation. Stimulation produced a large early peak that was positive on the scalp contralateral to the hemifield and negative on the ipsilateral scalp. From computer fitting of the amplitudes versus electrode position, the position of the equivalent source was found to be in the contralateral hemisphere. The horizontal orientation of the dipole source was approximately tangential (parallel) to the occipital scalp surface with negative polarity toward the medial fissure. In normal subjects, visual evoked potential amplitudes at the first peak were positive on the left and negative on the right for right hemifield stimulation. Left hemifield stimulation showed the opposite results. Three patients with homonymous hemianopia showed normal visual evoked potential results from their functional hemifields and nearly flat results from their hemianopic hemifields. The normal visual evoked potentials originated in their intact cortical hemispheres. PMID- 1505340 TI - The topographic distribution of the magnetic P100M to full- and half-field stimulation. AB - Visual evoked magnetic responses were recorded to full-field and left and right half-field stimulation with three check sizes (70', 34' and 22') in five normal subjects. Recordings were made sequentially on a 20-position grid (4 x 5) based on the inion, by means of a single-channel direct current-Superconducting Quantum Interference Device second-order gradiometer. The topographic maps were consistent on the same subjects recorded 2 months apart. The half-field responses produced the strongest signals in the contralateral hemisphere and were consistent with the cruciform model of the calcarine fissure. Right half fields produced upper-left-quadrant outgoing fields and lower-left-quadrant ingoing fields, while the left half field produced the opposite response. The topographic maps also varied with check size, with the larger checks producing positive or negative maximum position more anteriorly than small checks. In addition, with large checks the full-field responses could be explained as the summation of the two half fields, whereas full-field responses to smaller checks were more unpredictable and may be due to sources located at the occipital pole or lateral surface. In addition, dipole sources were located as appropriate with the use of inverse problem solutions. Topographic data will be vital to the clinical use of the visual evoked field but, in addition, provides complementary information to visual evoked potentials, allowing detailed studies of the visual cortex. PMID- 1505341 TI - The application of Laplacian analysis in the recording of half-field pattern onset evoked potentials. AB - The Laplacian operator in electroencephalographic measurements consists of a mathematical combination of the responses from a number of electrodes (e.g., five in a crosswise montage). It enhances activity from sources lying underneath the area covered, relative to activity from outside this area. Thus, by appropriate positioning, the contributions of extrastriate and striate sources can be recorded selectively. To quantify the contribution of each hemisphere to half field onset evoked potentials, the responses in two Laplacian operators, one over each hemisphere, were analyzed and compared to monopolar derivations and a bipolar derivation between the two hemispheres. Both the Laplacian and bipolar analyses were helpful in interpretation of the responses. PMID- 1505342 TI - Visual evoked potentials specific for motion onset. AB - Motion-onset visual evoked potentials were studied in 140 subjects by means of motion-onset stimulation either on a television screen or through back projecting via a moving mirror. The motion-onset visual evoked potentials were characterized in 94% of the population by a dominant negative peak with latency in the range of 135-180 ms. Motion-onset visual evoked potentials with a dominant positive peak, as described in the literature, seemed to be a variant of pattern-off visual evoked potentials, caused by the pattern-disappearance effect at the onset of motion with a high temporal frequency (the multiple of the spatial frequency of the structure and the velocity of motion) of more than 6 Hz. Such visual evoked potentials occur mainly when the stimulus is limited to the macular area only. Additionally, other stimulus and recording conditions were found to be suitable for acquiring the specific motion-onset potentials without their contamination by pattern-related components. These conditions were as follows: an aperiodic moving pattern (e.g., random dots) with a low contrast (less than 0.2); a short duration of motion (less than or equal to 200 ms) and a sufficient interstimulus interval (at least five times longer than the motion duration) to decrease the adaptation to motion; and extramacular stimulation and recording of visual evoked potentials from unipolar lateral occipital leads. Such leads should be used because of the lateralization of these visual evoked potentials (mainly to the right occipital area), which is consistent with their assumed extrastriate origin. PMID- 1505343 TI - The c-wave of the direct-current-recorded electroretinogram and the standing potential of the albino rabbit eye in response to repeated series of light stimuli of different intensities. AB - In 10 experiments on five albino rabbits, the direct-current electroretinogram and the standing potential of the eye were recorded in response to repeated light stimuli (duration, 10 s; interval, 70 s), presented in four series, each consisting of 25 light flashes. Light intensities were, in order of presentation to the eyes, 3, 2, 1 and 0 log rel units (series I, II, III and IV, respectively) below the maximum output of the system. Thirty minutes of dark adaptation preceded each series. At the end of series I, the mean amplitudes of the b- and c waves were higher and that of the a-wave relatively unchanged compared with the corresponding initial amplitudes. During series II-IV, there was a marked decrease in mean a- and b-wave amplitudes between the first and the following electroretinogram responses, and at the end of the three series, the amplitudes were still significantly reduced compared with the corresponding initial values. The mean c-wave amplitude was also markedly decreased immediately after the first electroretinogram recording, but it later recovered to a large extent. A peak in the c-wave amplitude was discerned about 14-18 minutes after the start of the recordings. A standing potential minimum during the second light stimulus was followed by a peak after about 10-13 minutes. The partially parallel behavior of the c-wave and the standing potential suggests the operation of a pigment epithelial mechanism behind the recovery of the c-wave amplitude. The final amplitudes of the b- and c-waves, and to a large extent also of the a-wave, were about the same irrespective of stimulus intensity. The adaptational processes in the rabbit appear to be more complicated than was previously thought. When electroretinogram amplitudes and standing potential levels are discussed and when one experiment is compared with another one, it is important that adaptational and stimulus conditions, as well as time course, are well controlled and clearly specified. PMID- 1505344 TI - [Proteinuria and atherogenic risk]. AB - The relationship between blood-lipid levels and severity of proteinuria was examined retrospectively in 30 patients (12 males, 18 females; mean age 39 [18 58] years). All patients had histologically confirmed glomerulonephritis (minimal change: n = 7, perimembranous: n = 8, focal sclerosing: n = 6, rapid progressive: n = 3, mesangio-proliferative: n = 4, membrano-proliferative: n = 1, diabetic glomerulosclerosis: n = 1). None was taking lipid-lowering drugs. Patients were classified according to the degree of proteinuria. In group 1 (proteinuria less than 5 g/d, n = 13) the LDL-HDL ratio averaged 4.4; in group 2 (proteinuria 5.0 10.0 g/d, n = 10) the average ratio was 8.8, and in group 3 (proteinuria greater than 10.0 g/d, n = 7) 13.3. Total cholesterol concentration also rose with increasing proteinuria (to 300 +/- 87 mg/dl, 375 +/- 168 mg/dl and 464 +/- 143 mg/d, respectively). The size of the LDL-HDL ratio and the level of total cholesterol did not correlate with the degree of excretory renal failure. These results point to an impressive correlation between the degree of proteinuria and the level of LDL-HDL ratio as a measure of atherogenic risk for a given patient. PMID- 1505345 TI - [Bleeding gastric and duodenal varicose veins: endoscopic embolisation using tissue adhesives]. AB - Endoscopically guided intravascular injections of the tissue glue N-butyl-2 cyanoacrylate have since 1990 been performed in eight patients (seven men, one woman; median age 59.5 [40-72] years) with cirrhosis of the liver (alcoholic: n = 6, posthepatic, n = 2), decreased haemoglobin (6-10 g/dl) and transient shock symptoms (n = 5) due to gastric (n = 7) or duodenal varices (n = 1). Gastric acid production was suppressed with omeprazole. Neither balloon catheters nor drugs were used to lower portal vein pressure. Initial haemostasis was achieved in all patients. One patient with consumption coagulopathy died of recurrent bleeding from varices in the body of the stomach which could be only temporarily arrested. Another patient had a recurrence of bleeding from varices in the cardia 3 months after the initial treatment: it was again controlled by endoscopic sclerotherapy with tissue glue. All other patients remain free of bleeding after a mean observation time of 8.4 months. PMID- 1505346 TI - [Diagnosis of autonomic diabetic neuropathies of the gastrointestinal tract]. PMID- 1505347 TI - [Transmitting patient data by telefax]. PMID- 1505348 TI - [Local therapy of chronic synovitis]. PMID- 1505349 TI - [Early summer meningoencephalitis vaccination]. PMID- 1505350 TI - [Mitral insufficiency after percutaneous balloon valvuloplasty in mitral stenosis. Incidence and progression]. AB - Percutaneous balloon valvoplasty of the mitral valve was performed in 126 patients (24 men, 102 women; mean age 55.0 +/- 12.1 years) with mitral stenosis. The mean transmitral valve gradient fell from 12.4 +/- 6.1 to 6.0 +/- 3.2 mmHg, while the valve opening area increased from 1.0 +/- 0.2 to 1.55 +/- 0.3 cm2. After percutaneous balloon valvoplasty 36 patients still had no mitral regurgitation, while the grade of mitral regurgitation remained the same in 47 (grade I: n = 35; grade I: n = 12). Mitral regurgitation, previously not present, occurred in 25 patients, but was severe in only three (grade III: n = 1; grade IV: n = 2). Previously present mitral regurgitation increased in 18 of 65 patients, in four to grade III, in one to grade IV. In three patients acute grade IV mitral regurgitation resulted from a tear in a leaflet of a fibrotic valve which was not or only slightly calcified, requiring emergency surgery. Followup observations over 16.9 (1-60) months showed no change in most patients, but three developed mitral regurgitation. The latter underwent elective surgery, as did one patient with acute mitral regurgitation. Thus a total of seven patients (5.6%) required surgery for mitral regurgitation after percutaneous balloon valvoplasty. PMID- 1505351 TI - [Diphtheria immunity in school beginners and after reimmunization with d vaccine]. AB - The antitoxin immune status against diphtheria was determined in 814 children, aged 6-7 years, 5-6 years after first immunization. All children were then re immunized with d-vaccine. 4-8 weeks later antitoxin was again measured to assess the immunogenic effect of the booster injection (reduced toxoid dosage of 5 IU/0.5 ml). Although all children had been completely immunized as infants, 149 of them (18.3%) presented inadequate or no immunity to diphtheria. The booster injection resulted in a reliably protective antibody concentration of 0.1 IU/ml serum even in children with low or no longer demonstrable residual immunity. The high proportion of inadequately protected children and the further continual loss of antitoxin antibodies makes booster injection mandatory at the time of beginning school as well as in juveniles and adults. The Standing Immunization Commission of the Federal German Health Office recommends this re-immunization every 10 years in the form of combined tetanus-diphtheria immunization with Td vaccine. PMID- 1505352 TI - [Endoscopic sonography in extrahepatic obstructive jaundice]. AB - In a prospective study, 37 patients (20 women, 17 men, mean age 75 [41-93] years) with extrahepatic obstructive jaundice were investigated, within 24 hours of admission, by transcutaneous ultrasound (US), endoscopic ultrasound (EUS) and endoscopic retrograde cholangiopancreatography (ERCP). EUS was always performed after US and immediately before ERCP, and the findings were recorded without any knowledge of the results of ERCP (the 'gold standard'). Dilatation of the common bile duct was demonstrated by all three methods. Concretions in the distal common bile duct causing obstructive jaundice were demonstrated by EUS in 15 out of 16 cases, but in only seven cases by US. All 21 cases with an underlying malignant cause were correctly diagnosed by EUS and ERCP, and the level of the biliary obstruction was accurately determined; using US this was possible in only 15 (70%) and 18 (85%) cases. In comparison with ERCP, which imaged the tumour only indirectly, EUS showed the tumour itself and allowed local and regional staging in all cases. EUS is superior to US for elucidating the cause of biliary outflow obstruction and allows reliable local and regional staging. It is of additional benefit in deciding on appropriate therapy. A disadvantage is the impossibility at present of undertaking surgical therapy during EUS investigations. PMID- 1505353 TI - [Fatal pulmonary embolism after lysis therapy in post-traumatic renal vein thrombosis]. AB - A 30-year-old man was hospitalized because of increasing dyspnoea for 4 weeks. Chest X-ray demonstrated an infiltrate in the right upper lobe and enlargement of the central pulmonary arteries. Lung perfusion scintigraphy revealed, typical of embolism, absent perfusion of the entire right upper lobe, as well as segmental embolism in the left upper and basal lobes. Phlebography of the legs and pelvis was unremarkable. Intravenous heparin treatment was begun (initially 1,250 IU/h, then dosage adjusted according to the partial thromboplastin time). Nonetheless the patient's condition deteriorated the next day and the respiratory failure increased (pO2 61 mm Hg despite oxygen supply). Streptokinase was then infused in ultra-high dosage, 9 million units over 6 hours. But the patient died of cardiocirculatory failure 4 hours after the streptokinase infusion had been finished. Autopsy revealed fulminant recurrent pulmonary embolism with occlusion of the right main pulmonary artery. The emboli had their origin in renal vein thrombosis extending into the inferior vena cava, which had probably been caused by slight trauma to the flank during a game of squash 6 weeks previously. PMID- 1505354 TI - [Therapy of autonomic diabetic neuropathy of the gastrointestinal tract]. PMID- 1505355 TI - [Sleep in the aged]. PMID- 1505356 TI - [Is ulcerative colitis an autoimmune disease?]. PMID- 1505357 TI - [Axillary hyperhidrosis]. PMID- 1505358 TI - [Fulminating pulmonary embolisms: thrombolysis versus thrombectomy]. PMID- 1505359 TI - [Secondary achalasia]. PMID- 1505360 TI - [Potassium restriction and essential hypertension]. PMID- 1505361 TI - [Scanning electron microscopic findings of the navicular bone and deep flexor tendon in podotrochlosis of horses]. AB - In 25 adult horses the podotrochlea of 49 forelimbs was examined by means of light and electron microscopy in order to correlate clinical and morphological findings. According to the clinical diagnosis the animals were divided into three groups: lameness due to syndrome of podotrochlosis (group 1) or due to tendopathy (group 2) and horses without lameness (group 3). The most striking pathological findings of the navicular bone and the opposite surface of the deep flexor tendon were found in horses with podotrochlosis, consisting of loss of cartilage and tendon matrix with denudation of collagen fibrils, superficial degeneration and necrosis, focal occurrence of fissures and far-reaching defects, sometimes accompanied by adhesions between tendon and navicular bone surface. In radiologically only slightly altered tendons and navicular bones light and scanning electron microscopy often revealed moderate to severe pathological changes, which sometimes could also be seen in clinically healthy horses. The distribution of the lesions indicate that in course of podotrochlosis the initial alterations caused by repeated microtraumata start at the surface of the deep flexor tendon and subsequently spread to the opposite facies flexoria of the navicular bone. An involvement of the cartilage and the synovial layer of the hoof joint in cases with podotrochlosis could only be rarely observed and is to regard as a secondary manifestation. PMID- 1505362 TI - [PCB concentrations in hair, blood, tissues and secretions of chronically-exposed dairy cows, fattening bulls and calves. 1. Course and relation of some polychlorinated biphenyls in hair, milk and tissues in exposed nursing cows and conventionally raised dairy cows]. AB - 20 cows contaminated chronically with PCB were kept as nurse cows or in a tie stall. The contamination in different substrates (hair, milk, blood, feces) was examined for a period up to 8 months. The distribution of PCB in the carcass of some animals was registered in addition. The system of keeping nurse cows turned out to be useful in order to overcome a contamination situation. Drying off gravid animals in the first step helps solving problems of handling contaminated milk. With low contaminated animals a short dry off period is sufficient, so that the milk--after calving--is marketable (report II, in preparation). In case of nurse cows with two calves post partum a continuous decline of PCB-concentrations in the milk can be observed. With biological half life periods of 2-4 months, milk with PCB 153-concentrations of 0.15-0.20 mg/kg fat will be marketable within this period. Cows milked by milking-machines show a decline of PCB in the milk similar to nurse cows. Two animals had a limited increase p.p., probably caused by mobilization of fat in the high lactation stage. Over longer periods, the biological half-life-periods were comparable to nursing cows. Hair is easy to sample and store; it is useful as a diagnostic substrate beside the milk in order to estimate the degree of contamination in individual animals. The ratio of PCB concentrations between perirenal fat and hair is 1:0.95 (s = +/-0.192); the ratio of PCB-concentrations between perirenal fat and milk is 1:0.77 (s = +/- 0.122).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1505363 TI - [Evaluation of fixed glucocorticoid-antibiotic combinations]. AB - Fixed combinations of glucocorticoids and antibiotics are widely used for the treatment of bacterial infections because they can cause a rapid relief of the inflammatory symptoms. However, hitherto a decisive improvement of the clinical efficacy of the combination as compared to single antibiotic therapy could not be proved. Without a real clinical advantage the combined use of glucocorticoids causes severe side effects like immune suppression with increased risk of infections, gastrointestinal lesions and depression of endogenous hydrocortisone which all will occur even after short-term use and may last for several weeks. Glucocorticoids exhibit a markedly longer duration of action than antibiotics with the risk of cumulation of the glucocorticoid. Thus, there is no kinetic compatibility as it has to be claimed for a rational combination. Due to the negative risk-benefit relation the systemic use of such combinations has to be rejected. For the topical treatment of skin disorders, however, the short-term use of combinations of corticosteroids and antibiotics with comparable pharmacokinetics on the skin like aminoglycoside antibiotics can be of clinical benefit. PMID- 1505364 TI - [Liver diseases of fattening bulls]. AB - The authors report on occurrence, causes and diagnostics of liver affections observed in fattening bulls in Ukrainia between 1982 and 1988. For this purpose, 2747 bulls in 10 fattening plants had been controlled clinically once during the last month of their final fattening period (lasting, according to the feeding schedule, from the 4th until the 12th, or from the 6th until the 18th month of life), and 1318 of them were controlled for eventual hepatic lesions at slaughter. The authors found an increase in liver affections during the final fattening period. The type of lesion found preferentially in the different fattening plants showed a certain correlation with feeding used in these: The prevalence of liver lesions (i.e. in 87.2% of the animals controlled) were found in fattening bulls fed cereal branstraw-pellets; among these, liver abscesses were most frequent (i.e. 55.2% of all lesions observed in this group). Steatosis of the liver was prevalent in fattening bulls receiving eating offalls (i.e. 82.7% of all lesions found in that group), whereas liver cirrhosis was prevalent in fattening bulls fed with sugar beet chips-silage. In Holstein-bulls, liver lesions were about double as frequent as in Fleckvieh-bulls (i.e. 37.3 and 16.7% of the livers controlled were found involved, respectively). Diagnostical value of several clinical parameters controlled is discussed (i.e. size and sensitivity of liver percussion field, activity of SDH, LDH, AST and ALT in serum, serum concentration of vitamin A, D3-25 and E, concentration of Vitamin A in liver, and concentration of cholic acids and of their glucoconjugates in bile). PMID- 1505365 TI - [Arnold Schell (1821-1900), departmental veterinarian and dozent of the Agricultural Academy in Bonn--contemporary historical profile of a personality]. AB - In the early 19th century numerous scientific educational institutions in the field of agriculture came into existence. Motives were new knowledges in agriculture, science and economics. After a transient establishment of an agricultural institute at the University of Bonn (1819-1826) in 1847 an independent academy of agriculture, later a college resp. a faculty were founded in Poppelsdorf nr. Bonn. Instructions on veterinary science, which was regarded as an auxiliary subject included animal diseases and anatomy as well as physiology of domestic animals. These subjects were taught for 48 years by Prof. Arnold SCHELL, honorary lecturer (1850-1898), being simultaneously Departmentstierarzt in Cologne and Kreistierarzt (district veterinary officer) in Bonn. SCHELL published articles with variable topics. He took an active hand as member of the executive committee (from 1860) and as head of the local section Bonn in the Landwirtschaftliche Verein fur Rheinpreussen. He organized the Verein Rheinpreussischer Tierarzte, and he was for many years its president. As delegate of this association he advocated the corporate concerns in the Deutsche Veterinarrat and in the Centralvertretung der tierarztlichen Vereine Preussens. SCHELL was a distinguished teacher and conveyor between veterinary science and agriculture, he was engaged in problems of animals husbandry and epidemic law, he contributed essentially to the development of the veterinary corporation. He was decorated with top honors as Kronenorden III. class and Roter Adlerorden IV. and III. class. PMID- 1505366 TI - [Leibniz and veterinary medicine--a contribution to Leibniz research]. AB - This study examines LEIBNIZ' idea of Veterinary medicine in a biographical context. It is based on material from the Leibniz-Archives of the Niedersachsische Landesbibliothek Hannover, primary sources as well as the correspondence between LEIBNIZ and F. HOFFMANN and B. RAMAZZINI. Critical analysis of LEIBNIZ' proposal to establish a medical administrative authority and an analysis of further sources corroborate the view of LEIBNIZ as a progressive thinker who included the epidemiology of veterinary medicine (the preventive approach) in his conception. In this way he conceived of veterinary medicine in scientific terms which is going to be the relevant approach today. PMID- 1505367 TI - Otitis media in children: to treat or not to treat. PMID- 1505368 TI - Acyclovir for the treatment of idiopathic vocal fold paralysis. PMID- 1505369 TI - Anterior skull base reconstruction with the pericranial flap after craniofacial resection. AB - No one reconstructive method is always satisfactory, especially when considering repair of a region such as the anterior skull base. Increased morbidity and mortality is directly related to failure of the reconstruction to adequately isolate the cranial cavity from the respiratory tract. Those surgeons performing craniofacial resections for lesions of the paranasal sinuses and anterior skull base must be familiar with a variety of reconstructive techniques which they can utilize depending upon the surgical defect that must be closed. For those small to moderate size defects of the anterior fossa we recommend using the inferiorly based pericranial flap to effect a repair. For larger defects extending laterally from the midline to involve a portion of the orbital roof, a laterally based flap of temporalis and pericranium can be used to provide successful anterior skull base reconstruction. Larger defects of the cranio-orbito-facial region will require additional methods of repair utilizing distant vascularized flaps. PMID- 1505370 TI - Management of head and neck burns. AB - Successful treatment of acute head/neck burns requires assessment and protection of the airway, prevention of further injury to damaged surface structures, and timely and diligent debridement and wound closure. Rehabilitation methods and modalities help to preserve function and control scarring. Reconstructive surgery should be designed to improve function and appearance, primarily by correction of the skin/tissue defect which healed by scar contracture. Thoughtful timing and application of logical surgical principles offer the opportunity of recovery to a level better than merely acceptable. PMID- 1505372 TI - Subglottic and tracheal malignancies. AB - Subglottic and tracheal malignancies are the least frequently encountered laryngeal cancers. When these tumors are encountered, they have often reached advanced size prior to producing symptoms. Once symptoms are brought to the attention of the otolaryngologist, rapid and accurate diagnosis is essential to effect the earliest possible treatment and to minimize morbidity and mortality associated with this problem. Illustrative cases are presented including a highly unusual case that presented with cardiac-like chest pain. A review of the literature including the pertinent anatomy, pathophysiology, and methods of diagnosis and treatment is presented. Increased familiarity with this disease process and a high index of suspicion on the part of the otolaryngologist may lead to improved survival patterns in patients with these malignancies. PMID- 1505371 TI - Loracarbef (LY 163892) vs amoxicillin/clavulanate in bacterial maxillary sinusitis. AB - Loracarbef (LY 163892), a beta-lactam antibiotic (carbacephem), was compared with amoxicillin/clavulanate potassium in a 10-day, single-blind, randomized parallel trial in the treatment of acute bacterial maxillary sinusitis. Based on posttherapy aspirate and culture, there was a 95.2% bacteriologic cure rate in patients receiving loracarbef (400 mg twice daily) and an 86.7% cure rate in patients receiving amoxicillin/clavulanate (500/125 mg three times daily) (p = 0.359). Loracarbef was comparable in efficacy to amoxicillin/clavulanate with a more desirable safety profile. PMID- 1505373 TI - Otogenic brain abscess: the Syracuse experience. AB - A review is presented of five cases of otogenic brain abscesses (from among 34 cases of brain abscesses of all causes) treated during a 16-year period at a major university hospital in upstate New York. Although the morbidity and mortality rates are high for patients with brain abscess, advances in the microbial isolation methods, specificity of antimicrobial agents, and earlier diagnosis by CT scans have all contributed to an improved outcome for this dreaded disease. PMID- 1505374 TI - Late development of lateral sinus vein thrombosis. AB - The incidence of lateral sinus vein thrombosis has been reduced by the use of antibiotics, but it is still a major complication of middle ear disease. Patients without active acute or chronic middle ear infection, however, develop this deadly complication. CT scan is helpful in diagnosis, but mostly the final diagnosis is made by surgical exploration. A case of a 23-year-old patient who developed lateral sinus vein thrombosis without an active middle ear disease is presented. The pertinent literature is discussed. PMID- 1505375 TI - Recurrent meningitis and a congenital perilymph fistula. AB - In any child with recurrent meningitis, the presence of a congenital perilymph fistula must be entertained. All of the patients must have an audiologic assessment, and if a sensorineural loss is demonstrated, CT of the temporal bones should be performed. CT is excellent in identifying malformations within the temporal bones, fistulous tracts, soft tissue densities in the middle ear, and defects in the tegmen tympani. Although MRI may provide superior discrimination of the audiovestibular and facial nerves and cerebellopontine angle, presently it does not offer any distinct advantages over CT in evaluation of the inner ear. When a fistula is suspected, an exploratory tympanotomy is recommended, and any CSF leak is sealed with muscle. PMID- 1505376 TI - CSF anatomy with emphasis on relations to nasal cavity and labyrinthine fluids. AB - Cerebrospinal fluid, occupying the subarachnoid space, is elaborated in an active process by the choroid plexus. It supports the brain and spinal cord and acts in lieu of a lymphatic system for central nervous tissue. Whether or not absorption of CSF into dural venous sinuses is an active or passive process is still controversial. A very thin layer of bone separates the posterior ethmoid air sinus from the subarachnoid space. There appears to be potential in man for flow of cerebrospinal fluid into the perilymphatic space of the inner ear, but it seldom occurs. PMID- 1505377 TI - Neurosurgical approaches to cerebrospinal fluid rhinorrhea. AB - The evolutionary concepts of pinpointing and treating cerebrospinal fluid (CSF) fistulas over the past few decades are reviewed taking into consideration the dynamic character of CSF circulation. The localization of the site of leakage is greatly facilitated by the judicious use of a variety of radioisotope and radiological techniques. The most recent are Metrizamide CT Cisternography and Magnetic Resonance Imaging. It is asserted that still the most challenging cases are those with intermittent liquorrheas, and those patients in which the site of the fistula is not easily defined. The authors will describe their personal experience with intracranial surgical repair of fistulas located in the anterior fossa. PMID- 1505378 TI - Complications of interstitial radioactive iodine implants for recurrent pituitary adenomas. AB - Three cases of recurrent pituitary adenoma elected to be treated with I125 implants are presented. The I125 implants caused significant delayed changes in the tissues surrounding the sella turcica which lead to the development of refractory cerebrospinal fluid (CSF) rhinorrhea. All three cases developed meningitis and two had pneumocephalus. This complication lead to the death of two patients and required intensive therapy in the third to achieve recovery. PMID- 1505379 TI - Extracranial approaches to the repair of cerebrospinal fluid rhinorrhea. AB - This paper presents a review of the extracranial evaluation and treatment of cerebrospinal fluid (CSF) rhinorrhea. Diagnosis with attention to a careful history and physical with maneuvers which exacerbate drainage and thorough physical exam along with imaging techniques are discussed. The common etiologies of CSF rhinorrhea including trauma, spontaneous leakage, tumor, and iatrogenic injury are included. Management consists of conservative measures including the avoidance of straining maneuvers which increases intracranial pressure. Periodic drainage of CSF via lumbar puncture or continuous drainage via flow-regulated systems may also be of benefit in attempts of conservative management. Failure of conservative management, constant leakage, pneumocephalus, and recurrent meningitis are indicators for surgical repairs. Ethmoid-cribiform plate region repairs are generally approached by external ethmoidectomy and the development of mucoperiosteal flaps from various donor sites which are then rotated to the leak area to seal the defect. Frontal sinus leaks are usually repaired via an osteoplastic flap technique with direct repair of the dural defect or the use of fascial graft tucked under the bony defect, then obliterated with abdominal fat. CSF rhinorrhea presents a diagnostic and surgical challenge to the otolaryngologist. After diagnosis and localization, operative repair using extracranial approaches is accepted as the initial method of intervention in these cases. PMID- 1505380 TI - Cerebrospinal fluid rhinorrhea: a review of the literature. AB - CSF rhinorrhea may be spontaneous or traumatic, the majority of cases being traumatic and presenting within the first three months. Spontaneous leaks imply an underlying abnormality which must be identified prior to treatment. Diagnosis and identification of the site of the leak is often inaccurate, even with meticulous care given to placing and removing the nasal pledgets. Once the leak is identified, medical or surgical treatment may be attempted. Recurrent leaks are common and serial operative procedures have been reported to stop even small leaks. PMID- 1505381 TI - Spontaneous cerebrospinal fluid rhinorrhea. AB - The diagnosis of CSF rhinorrhea requires the performance of a thorough history and physical examination. Often no objective findings can be found and further evaluation will be required. In our experience, metrizamide CT cisternography yields the most information for localization of the fistula. When indicated, patients can be protected against meningitis by using prophylactic antibiotics for 4-6 weeks to allow a fistula to close spontaneously. If the fistula fails to close during this time, surgical closure with dural or muscle graft with or without waxing of the bone is the treatment of choice. PMID- 1505382 TI - Assessment of medical impairment: problems v diabetes traumatic. AB - The modern concept of diabetes is first considered, i.e a susceptibility to diabetes which can be inherited. The environment may then interact with this susceptibility to determine which persons actually develop clinical complaints and the timing of its onset. The clinical types of established potential and latent diabetics are described together with the proof required for trauma to be accepted as a cause of diabetes rather than exposing a previous diabetic or latent state. Despite an extensive search of the literature and questioning of experts both in Kenya and outside, in the absence of predisposing factors no evidence of trauma being the direct cause of the diabetic syndrome has been found. The one exception may be where there has been definite gross physical injury to the pancreas, but even in this case the evidence is scanty and not very convincing and such cases must be very rare. Trauma may precipitate latent diabetes and its complications and make control more difficult. A percentage assessment is suggested. PMID- 1505383 TI - Reference values for FEV1 and FVC in male adolescents and young adults of Ibo origin. AB - Forced vital capacity (FVC) and one second forced expiratory volume (FEV1) were measured in 245 healthy Nigerian Ibo males aged 12-23 years. Analysis showed strong correlation between anthropometric factors (age, height, weight) and spirometric measurements (r----0.808-0.994). In the young adult group (18-23 years), FEV1 did not correlate so strongly with weight, however (r----0.654). Prediction equations, based on age and height have been developed for use among male Ibo adolescents and young adults. PMID- 1505384 TI - Acute renal failure as seen at Kenyatta National Hospital. AB - Forty seven patients with acute renal failure were studied prospectively over a two-year period at the Kenyatta National Hospital. There were 20 males and 27 females. The mortality rate was 40.4%. Most patients had medically oriented problems. Complications that were associated with a high mortality were infections and the presence of neuropsychiatric manifestations. PMID- 1505385 TI - Keloids: a study of the immune reaction to sebum. AB - A controlled study of the "immune reaction to sebum" pathogenesis of keloids was carried out at the University College Hospital, Ibadan, Nigeria; on 22 humans using a homogenate solution of liquid paraffin and vernix caseosa from neonates. The 22 human volunteers comprised two groups, 11 of which were keloid formers and 11 non keloid formers. 0.1cc of sterile liquid paraffin was injected intradermally into the anterior aspect of the left forearm. The mean reaction in keloid formers was 11.55mm while in non keloid formers, it was 8.18mm. Although a higher reaction was demonstrated in this study, in keloid formers, this was found not to be significant (p less than 0.05), thus suggesting that sebum may not be an important factor in the pathogenesis of keloid. PMID- 1505386 TI - Insulinoma in pregnancy presenting as a seizure disorder: a case report. AB - We present the clinical course and problems in the management of a 30 year old Nigerian lady who was admitted with fasting hypoglycaemia due to a pancreatic islet cell tumour (insulinoma) during the first trimester of pregnancy. Her case was initially misdiagnosed as idiopathic epilepsy. The outcome was fatal mainly because the poor clinical state of the patient limited our treatment options. This condition though uncommon, is potentially easily recognisable and treatable, as long as there is a high index of suspicion. PMID- 1505387 TI - Current concepts in motor neuron disease. PMID- 1505388 TI - Unusual form of motor neuron disease in Kenya. AB - Over the period November 1978 to October 1988, 46 cases of motor neuron disease were seen at Kenyatta National Hospital, Nairobi. One case was seen in private practice. A bimodal age distribution of the disease was identified with a peak in the fourth decade of life and another peak in the sixth decade of life. The disease seen in the fourth decade of life was different as seen in other parts of the world in that the majority of patients tended to present with very rapidly progressive disease despite the primary presentation with limb symptoms and signs. Serum cholinesterase activity in five of these patients and five of the classical motor neuron disease revealed no abnormalities. This unusually rapidly progressive disease in young adults has not been described anywhere. The disease seen in older age groups and especially in patients over fifty years of age was not different from the one seen in other parts of the world. PMID- 1505389 TI - Cerebellar ataxia in childhood: a review of clinical features, investigative findings and aetiology in 30 cases. AB - The symptoms, neurological deficits and aetiology of cerebellar ataxia were reviewed in 30 children aged from 4 to 16 years, who had been extensively investigated. Fourteen (46.6%) children had perinatal problems, and in 6 (20%), ataxia resulted from these perinatal events. Besides unsteady gait, a common presenting complaint was delayed motor milestones, noted in 15 (50%) patients. In most children (76.6%), clinical examination indicated involvement of more than one of the three main cerebellar divisions, viz archicerebellum, paleocerebellum and neocerebellum. Hypotonia, found in 11 (36.6%) children, was the third most common sign after gait and truncal ataxia. A variety of aetiological factors was identified, the two most frequent being hydrocephalus in 7 (23.3%) children, and perinatal problems in 6 (20%). The findings are discussed against the background of current literature on the subject. PMID- 1505390 TI - Rarity of dementia (by DSM-III-R) in an urban community in Nigeria. AB - Dementia of the elderly, a public health problem world-wide, is underdocumented in black Africa. We carried out a door-to-door survey in Idikan in NW3 ward, a political and administrative unit, with a population of 9000: in Ibadan city, Nigeria, to determine the burden of dementia. Census and demographic listing was done by trained clinical students who concurrently administered a modified Mini Mental State Examination as a screening instrument to those aged 40 years or more. Only 2 out of 932 subjects refused: 293 (31%) were aged 65 years or more. Those who were positive to the screening test and 20% of negatives were investigated by neurologists. Decline in cognitive function significantly correlated with age, female sex and low level of education. Impaired cognition was present in 41 (4.4%) but was due to depressive disorders in 7 (0.6%) patients. In none of the remaining 34 (3.8%) subjects could a diagnosis of dementia as defined by DSM-III-R be justified. PMID- 1505391 TI - Bacteraemia in febrile out-patient children. AB - In order to study the occurrence of bacteraemia, 634 consecutively febrile children aged less than or equal to 14 years with Initial rectal temperature or 39 degrees C and above were evaluated. The overall frequency of bacteraemia was 7.7% (49 cases). Salmonellae, Streptococci and Staphylococci accounted for 57%, 16% and 14% respectively. No statistically significant difference was noted between cases and controls with regard to the nutritional status mean age in months +/- SD (55.9 +/- 49.1 vs 39 +/- 41), and haemoglobin levels in g/dl +/- SD (11.1 +/- 1.5 vs 11.1 +/- 1.5) (P greater than 0.05). None of the parameters studied was a strong predictor of bacteraemia and systemic bacterial infection did not strongly correlate with the magnitude of the clinical illness. PMID- 1505393 TI - Megaloblastic anaemia in Zimbabwe: spectrum of clinical and haematological manifestations. AB - An analysis of 100 cases (43 males and 57 females) with confirmed megaloblastic anaemia is presented. The age distribution showed two peaks with 18% in the third and fourth decades and 25% in the seventh decade. Anaemia of moderate to severe degree occurred in all patients and accounted for the commonest triad of symptoms at presentation viz: weakness (73%); breathlessness (40%) and headaches (33%). Macrocytosis or macroovalocytosis and neutrophil hyper-lobulation were found in all cases; MCV greater than 100fl in 84%; pancytopenia in 47%; and megaloblastic haematopoiesis found in all patients varied from moderate to gross in severity. Thus, the finding of macrocytic anaemia with a high MCV particularly in excess of 100fl, neutrophil hypersegmentation, and characteristic megaloblastic changes in the bone marrow should dictate further appropriate investigations to help in establishing the specific diagnosis if appropriate therapeutic intervention is to be ultimately instituted. PMID- 1505392 TI - Clinical and bacteriological study on childhood empyema in south eastern Nigeria. AB - Forty-eight children with empyema thoracis were seen over a seven-year period (December, 1982 to November 1989) in the University of Calabar Teaching Hospital, Calabar, Nigeria. This number accounted for 0.2% of all paediatric admissions during the period. The peak age incidence was 2 years and under. Pneumonia was the antecedent illness in about all cases, but surprisingly, measles played an insignificant role. Late consultation and severe morbidity were constant feature with anaemia and cardiac failure as frequent complications of the disease. Staphylococcus aureus, the predominant causative organism was resistant to penicillin and ampicillin but sensitive to gentamicin, cloxacillin and erythromycin. The initial use of the parenteral gentamicin or cloxacillin in treating children with empyema is therefore recommended. This study demonstrates the rarity and low fatality (6%) of childhood empyema in Calabar, but protracted hospitalisation and exorbitant medication involved make it an important disease. Perhaps, it can be completely eliminated if parents are educated enough to avoid late reporting of childhood respiratory disease. PMID- 1505394 TI - Comparative study of superficial cancer in Tanzania. AB - Examination of the Tanzania Cancer Registry from 1978 to 1988 showed squamous cell carcinomas to be the most frequent form of superficial malignancy, followed by Kaposi's sarcoma and then malignant melanoma. Males were more afflicted than females, and the lower limbs were predominant sites of the lesion. In terms of relative importance of various types of superficial cancers, the pattern seen in Tanzania was similar to that in another East African country. In a West African country, Kaposi's sarcoma was not common. On the other hand, among blacks in the USA, basal cell carcinomas were almost similar in frequency to squamous cell carcinomas. PMID- 1505395 TI - Consanguineous marriages in the province of Trabzon, Turkey. AB - This study involved 999 married women, aged between 15 and 49, at the twelve health centres in the province of Trabzon in order to determine the ratio of consanguineous marriages, the factors affecting this situation, the ratios of abortion and the mortality of children in the first year. This ratio of consanguineous marriages was found 20 percent. The education levels of the great majority of these were low. The average age was 18. These were most frequently between children of paternal aunts and maternal uncles (39%) and these marriages, the ratio of abortion and children mortality were higher than others (P less than 0.05). Furthermore, it has been established that the kind of marriage has considerably decreased in Trabzon lately, but we believe that this reduction will be higher in the future since the education levels rapidly increase. PMID- 1505396 TI - Adult empyema in Zaria, Nigeria. AB - The clinical records of 41 adult patients who were treated for empyema thoracis at the ABU Hospital, Zaria from 1974 to 1986 have been reviewed. Twenty six (63%) of the patients were younger than 34 years. Bacterial pneumonia, pulmonary tuberculosis and chronic bronchitis were the underlying illnesses in 32 (78%) while advanced malignancies were present in two others. Gram-negative bacilli were as important as the gram-positive cocci as causative agents in the 16 patients whose pleural aspirates were culture-positive. Closed chest tube drainage was most often effective when combined with antibiotics. Overall, 5 patients died, 2 absconded, 34 were discharged home but the default rate from the follow up clinic was high. PMID- 1505397 TI - Microbial contamination of commercial food products: fact or fiction. PMID- 1505398 TI - Raw milk as a source of enterotoxigenic Staphylococcus aureus and enterotoxins in consumer milk. AB - Staphylococcus aureus strains were isolated from 183 of 300 raw milk samples collected at the Kenya Co-operative Creamery (Dandora). 97 of these 183 trains were assayed for the production of enterotoxin A, B, C and D. Seventy two (74.2%) of these were found to produce either a single or a combination of enterotoxins. Raw milk is a potential source of enterotoxigenic S. aureus in milk and milk products, especially if there is defective pasteurisation. PMID- 1505399 TI - Layman's perception of antimicrobial agents: a challenge to health education strategy in Zimbabwe. AB - In many developing countries there has not been any systematic analysis of societal beliefs and attitudes towards drug entities, the meaning which is attributed to drugs and their effects and how such meanings might influence drug consumption and health seeking behaviour. It is in many developing countries that a lot of antimicrobial agents are available freely over the counter or on the street. This is said to make the assessment of the therapeutic outcome during their use often very difficult. The present study has shown that continued health education while at the same time paying attention to societal beliefs and attitudes towards infectious diseases and medicines used, is required. The specific aims must be to reinforce beliefs that facilitate appropriate use of antimicrobial agents and to discourage those that impede it. PMID- 1505400 TI - Disk diffusion antimicrobial assays of agents used in respiratory tract infections in intubated patients admitted to the intensive care unit (ICU) of Kenyatta National Hospital from November to December 1990. AB - Sensitivity patterns of bacterial isolates from respiratory tract infections to benzylpenicillin, gentamicin and ceftazidime were studied. In a period covering 8 weeks from November to December 1990, tracheal aspirates from a total of 22 intubated patients aged 6-54 years were taken. The duration of stay of patients in the unit by the time of specimen collection ranged from 2-92 days. Respiratory tract infections by pathogenic organisms set in earliest on day 4. Elevated temperatures (equal to or greater than 38 degrees C) and/or purulence in sputum were used as diagnostic indicators of respiratory tract infections. A total of 12 pathogenic organisms were obtained: Proteus spp, Pseudomonas spp, Klebsiella spp, Acinetobacter spp, Escherichia coli and Staphylococcus aureus. None of the 12 pathogens isolated was sensitive to benzylpenicillin; 50% of organisms were sensitive to gentamicin and all were sensitive to ceftazidime. PMID- 1505401 TI - Escherichia coli associated with acute measles and diarrhoea at Kenyatta National Hospital, Kenya. AB - Three hundred and three children under 5 years old with acute measles and diarrhoea (cases) and 300 other age-matched children with diarrhoea (controls) were examined for enteroadherent E. coli (EAEC) and other agents including rotavirus and Cryptosporidium. EAEC was determined by tissue culture of HEP-2 cells. Other agents were determined by conventional methods. EAEC was identified from both cases and control accounting for 10.3% (31/303) and 15.2% (46/300) respectively. Other bacterial agents were: 10.3% (31/303) from cases and 12.8% (39/300) from controls. A higher detection rate of enteroparasites was found among cases 15% (45/300) than controls 8.9% (27/300) whereas rotavirus was the reverse, 3% (9/303) in cases and 30.3% (92/300) in controls. To our knowledge characterization of EAEC has not been done before and therefore might be attributing factor to some of our unexplained diarrhoeal cases. PMID- 1505402 TI - Nigerian secondary school teachers: a pilot survey of views and knowledge about drug abuse. AB - The views and knowledge level of 135 randomly selected Secondary School teachers in the Abeokuta Local Government area of Ogun State on drug abuse were sought through a self report anonymous questionnaire. They were mostly male teachers (59.3%) under the age of 30 years (89.6%). The majority (59.3%) were never exposed to drug education as students whilst less than 20% have been exposed since qualifying as teachers. 72.6% do not currently teach their students Drug education. Although the majority had a good concept of the definition of drug abuse, their view on the potential drugs of abuse and the concept of "drug dependence" were inadequate. Respondents recently exposed to drug education were more likely to identify salicylate analgesics as potential drugs of abuse at a statistically significantly level (p less than 0.05). 85.9% of the respondents chose "guidance counselling" as the approach to the management of student drug abusers despite the dearth of this professional cadre in the schools. The disquieting implications of these findings in relation to the National Campaign aimed at stemming the increasing tide of drug abuse among youths in the country were discussed and suggestions proffered on ways of rectifying these. Finally the authors gave suggestions on the pattern and content of teacher-targetted formal drug education programme in the light of the findings. PMID- 1505403 TI - ABO blood groups distribution in relation to hepatitis B surface antigen and the presence of lipoidophil antibodies. AB - Three hundred and thirty donors were screened for HBs Ag using direct passive haemagglutination and the presence of Lipoidophil antibodies as detected by VDRL test. Blood group O donors had the highest HBs Ag prevalence rate of 4.3% as against the 0% frequency for group AB donors. There were no significant association between ABO blood group distribution and the presence of HBs Ag (P greater than 0.05). 11 donors in all were positive for HBs Ag giving a total prevalence of 3.3%. The sera of 27 blood donors (8.2%) contained lipoidophil antibodies. The highest percentage of VDRL test positivity was in blood group B donors (22.7%) followed by group O (9.1%). None of the 6 group AB donors had a reactive sera. Test of significance showed that there was no association between ABO distribution and the presence of lipoidophil antibodies. In conclusion, it is stated that since none of the blood donors that was reactive to the VDRL reagin carried HBs Ag, hepatitis virus B unlike other viral infection, may not elicit the production of lipoidophil antibodies. PMID- 1505404 TI - Assessment of blood compatibility of haemodialysis membranes using a miniature flat sheet dialyser. AB - Available pre-clinical techniques of assessing severity of untoward reaction by blood following contact with haemodialysis membranes do not account for the effects of dialysate and flow characteristics in the observed blood changes. A miniature flat sheet dialyser that considered these effects was prepared and tested in both in-vitro and ex-vivo circuits. Changes in platelets and leucocytes in heparinised human blood in-vitro tests did not distinguish regenerated cellulose (Cuprophan 150PM) membrane from a synthetic membrane, a copolymer of acrylonitrile and sodium methyl sulphonate (AN69S). Ex-vivo tests using rats showed more marked leucocyte (41.3%) and platelet (43.1%) depletion by Cuprophan 150PM than AN69S after 90 minutes of dialysis. Leucocyte and platelet loss due to AN69S were 26.9% and 13.4% respectively. In addition, Cuprophan 150PM membranes exhibited high affinity for leucocytes and platelets in both in-vitro and ex-vivo tests compared to AN69S membranes which were primarily covered with erythrocytes. Application of simulated in-use techniques in preclinical evaluation of blood compatibility membranes that are used in extra-corporeal treatment are recommended. PMID- 1505405 TI - Experience with carbimazole in the drug treatment of the hyperthyroidism of Graves' diseases in Nigerians. AB - To estimate the rate of remission of relapse in patients with thyrotoxic Graves' disease following therapy with thionamides, the course of 49 patients who were treated with carbimazole and followed personally for a mean (+/- SD) of 22.0 +/- 17.8 months, was analysed. A remission rate of 61% was obtained. Remissions were more common in patients with small goitres and those with a short duration of illness. Relapse, which was infrequent, occurred mostly within a few months following the discontinuation of the drug. 32% of the patients left the clinic either before or soon after achieving euthyroidism. It is concluded that carbimazole is quite efficacious in the induction or remission in newly diagnosed Nigerian patients with toxic Graves' disease and, at the present time, should probably be the principal treatment modality for these patients rather than subtotal thyroidectomy. Efforts should be made to reduce the frequent drop-out of our patients from the clinic during follow-up. PMID- 1505406 TI - The response to varied timing and spacing of tetanus toxoid administration in pregnancy. AB - One hundred and sixty-eight pregnant women at the University of Nigeria Teaching Hospital, Enugu, Nigeria, were studied for their response to varied timing and spacing of tetanus toxoid administration. In patients who started immunization before the third trimester of pregnancy, the longer the interval between the two doses, the better the response. In contrast, when immunization was started in the third trimester, the longer the interval between the two injections, the poorer the response. In all cases, the presence of antitetanus antibodies at booking conferred better response. In addition, the titres of antibodies in all patients who responded continued to rise till delivery. The significance of these findings is discussed and recommendations made. PMID- 1505407 TI - Meconium aspiration syndrome--unusual features. AB - A term infant with the meconium aspiration syndrome (MAS) is described. He had the typical clinical course of the disease despite appearing well nourished, and with good Apgar scores. At 5 months of age, he continued to do well with no sequelae. The reason for the initial passage of meconium in-utero remained speculative. The fact that the disease is preventable is emphasised. PMID- 1505408 TI - Primary hypothyroidism with secondary hypertension: a case report. AB - Both primary hypothyroidism and secondary hypertension are thought to be relatively uncommon in most parts of the tropics. A Nigerian hypothyroid patient with thyroxine-responsive hypertension is reported, and this syndrome (secondary hypothyroid hypertension) is examined with respect to its possible aetiopathogenesis. PMID- 1505409 TI - Modern concepts in the management of flail chest. AB - Seven patients with varying degrees of paradoxical chest wall movement (flail chest) were managed conservatively at the University of Port Harcourt Teaching Hospital with frusemide, methylprednisolone, non administration of crystalloid fluids and limitation of fluid intake. Patients showed considerable improvement within the first 24-48 hours which was sustained throughout the period of management. All seven survived and showed no signs of respiratory distress in the resting state or while performing simple exercise. One patient however had slight to moderate chestwall deformity. PMID- 1505410 TI - Giant twin sialoliths presenting with acute cellulitis: a case report. AB - Sialolithiasis is a process of unknown aetiology in which calculus concretions form in the salivary gland ducts and tissue. It may occur at any age but it is most common in middle-aged adults. A case is presented of the occurrence of double giant sialoliths in the left Wharton's duct in a 16-year-old boy. The clinical symptoms and signs were somewhat atypical and included acute suppurative cellulitis in the floor of the mouth plus localized periodontitis involving 36. Under a local anaesthetic the stones were surgically extracted and healing was uneventful. Proper interpretation of symptoms and thoughtful investigation for localization of salivary stones is emphasized. PMID- 1505411 TI - Malaria prophylaxis. PMID- 1505412 TI - The effect of participatory school health programme on the control of malaria. AB - Two hundred primary level school children, aged between 7 and 18 years took part in a comparative pilot study of the effect of participatory school health education in Kisumu, Western Kenya in 1988. An experimental cohort of 100 pupils had participatory health education versus a passive control of another 100. An initial KAP survey revealed comparable sociological variables as well as morbidity statistics. No significant change occurred on the knowledge of the disease between the groups after 3 months. However, positive change in attitude here determined by positive antimalarial practices, was observed more frequently in the experimental group than in the control group. Efforts to environmental manipulation increased by 69% vs 1%, while parasite rates decreased by 32% vs an increase of 5%, respectively. Similarly there was a decrease in absenteeism of 25% vs an increase of 5% between the groups. Clinical malaria was reported less frequently in the experimental group than the control (26% against 8%). In conclusion, this pilot study suggests that participatory approach in effective health education to school children should be investigated further to determine its potential in the intersectoral malaria control strategy. PMID- 1505413 TI - Efficacy of dapsone with pyrimethamine (Maloprim) for malaria prophylaxis in Maputo, Mozambique. AB - In a randomized controlled study of malaria prophylaxis, dapsone-pyrimethamine at a weekly dosage of dapsone 50-100 mg with pyrimethamine 6.25-12.5 mg or placebo was administered to 166 school children for 17 weeks. Fortnightly parasitological controls revealed 28 infections in the placebo group and none in the dapsone pyrimethamine group. It is concluded that weekly dapsone-pyrimethamine is effective for the prophylaxis of falciparum malaria in Mozambique. PMID- 1505414 TI - In vivo and in vitro response of Plasmodium falciparum to chloroquine in pregnant women in Kilifi district, Kenya. AB - In a malaria-endemic area of the Coast of Kenya with chloroquine resistant Plasmodium falciparum, we determined the prevalence and density of falciparum infection in gravid women and assessed the in vivo and in vitro parasite response to a regimen of chloroquine 25 mg/kg body weight divided over three days. P. falciparum infections were present in 65 (21.7%) of 300 pregnant women. The proportion of primigravidae who were parasitaemic was 41.8% which was significantly higher than that of the multigravidae (17.1, P less than 0.01). Primigravidae did not show a significantly higher mean parasite density than the multigravidae. The in vivo tests showed that 45.9% of all the P. falciparum infections were resistant to chloroquine predominantly at RI and RII levels with percentages 36.1% and 8.2%, respectively. PMID- 1505415 TI - Prevalence and frequency of Giardia lamblia in children aged 0 to 60 months with and without diarrhoea. AB - Stool specimen results from children with diarrhoea and without diarrhoea, in a rural village community in Kenya, were analysed in order to compare prevalence and age frequency distributions of Giardia between the 2 groups. There was evidence for 2 age-related prevalence peaks for Giardia in children 60 months and below. Furthermore, there appeared to be a clear Giardia-diarrhoea relationship in the age group of 19 to 24 months. PMID- 1505416 TI - Frequency of isolation of Cryptosporidium oocysts in Ethiopian children with acute diarrhoeal disease. AB - Stool specimens from one hundred children with acute diarrhoeal disease seen at the Gondar College of Medical Sciences Hospital, north-western Ethiopia were prospectively screened for the presence of oocysts of Cryptosporidium species. The study was conducted between June 1989 and January 1990. Nine out of one hundred specimens were positive for oocysts of Cryptosporidium. This study has demonstrated the presence of this parasite in the study region. A well desgned case control study is recommended to elucidate its clinical manifestations and association with malnutrition. PMID- 1505417 TI - A preliminary study on intermediate snail hosts of schistosomes in River Enyau, Arua district, Uganda. AB - A total of 1260 snail intermediate hosts of both Schistosoma mansoni and Schistosoma haemotobium were collected along the non-seasonal River Enyau which lies half a kilometre west of Arua, a north-western Uganda town. The snails collected were Biomphalaria pfeifferi 709: Biomphalaria choanomphala 457, Bulinus Bulinus tropicus 94. These were screened for cercariae shedding and 25 B. pfeifferi and 12 B. choanomphalal shed mammalian cercaricae while none of the Bulinus (Bulinus) tropicus shed any cercariae. River Enyau Biomphalaria snails were susceptible to a Schistosoma mansoni strain from Entebbe. Cercariae derived from these snails and also those found infected in the River Enyau were confirmed to be S. mansoni using laboratory mice. PMID- 1505418 TI - Arterial blood gases and acid-base status of adult patients presenting with acute severe asthma at Kenyatta National Hospital, Nairobi. AB - Forty adult patients with acute severe asthma were assessed for arterial blood gases and acid-base changes at presentation at the Casualty Unit, Kenyatta National Hospital, Nairobi, Kenya. Marked degrees of hypoxaemia (mean P(a)O2 of 8.02 kP(a)), hypocapnia (mean P(a)CO2 of 4.62kP(a)) with apparently normal pH (mean 7.384) were documented in the majority of these patients. Based on these findings, a significant number of the patients (68.5%) were either candidates (5.3%) or potential candidates (63.2%) for artificial ventilation. Records at this hospital suggest an increasing trend in asthma admissions and mortality. Additionally, Intensive Care Unit (ICU) admissions for asthma are associated with high mortality (54.4%). Pulsus paradoxicus emerged as the most significant (p = 0.002) clinical correlate to asthma severity. Central cyanosis was detected in none of the study patients suggesting that it is an unusual finding in the common presentation of acute severe asthma at this hospital. Its clinical detection would therefore imply an ominous clinical state. It is recommended that clinicians should take every opportunity to adequately assess their asthma patients before prescribing medications. They are also encouraged to more frequently request for blood gas studies in acute asthma. Those in charge of clinical teaching should direct appropriate efforts towards improved understanding of the pathophysiology and interpretation of acid-base disorders. PMID- 1505419 TI - Kagera 1989 health survey: 1. Human immunodeficiency virus seroprevalence in adolescents. AB - One thousand four hundred and fifty five adolescents were surveyed for Human Immunodeficiency Virus (HIV) infection in an area experiencing AIDS epidemic. The study was done in order to estimate control measures. Among the 1455 adolescents serosurveyed, 47 (3.2%) were HIV infected, of whom 30 (63.8%) were all aged 10-15 years old. The male/female ratio was 1:1. Of all the adolescents examined 830 (57.1%) were attending school. Among the selected potential risk factors namely non-school enrollment, illicit injections, blood transfusion and sexually transmitted diseases none of these was significantly associated with HIV seropositivity. Special care should be taken when interviewing adolescents on sensitive issues like the ones associated with HIV infection. In this study potential risk factors for getting HIV infection were rarely reported, thus making it difficult to get significant association with the HIV infection. PMID- 1505420 TI - In vitro experimental antileishmanial potential of ethylenediamine tetraacetic acid, disodium salt. AB - Leishmania donovani promastigotes (NLB 065) were treated to various concentrations of ethylenediamine tetraacetic acid (EDTA), disodium salt for 7 days. Concentrations of up to 1.0 mg/ml produced no significant reduction in the population of Leishmania promastigotes cultured in RPMI 1640 medium supplemented with 15% foetal calf serum and incubated at 27 degrees C (P greater than 0.05). Concentrations between 0.05 and 0.1 mg/ml EDTA did not significantly affect the viability of Balb/c mouse peritoneal macrophages (P greater than 0.05) whereas those equal to or above 0.2 mg/ml were severely toxic to macrophages (P less than 0.05; n = 8). Leishmania parasites engulfed in mouse peritoneal macrophages were treated to various concentrations of ethylenediamine tetraacetic acid (EDTA) disodium salt. The higher the EDTA concentration within the acceptable toxic levels for macrophages (less than or equal to 0.1 mg/ml), the higher was the rate at which parasites were cleared (p less than 0.05). The length of time in days within which infected macrophages were treated contributed significantly to a decline in the level of parasite-loads (P less than 0.05; n = 10). Analysis of mean metal ion values in mg/1 using atomic absorption spectrometry revealed that the levels of calcium, magnesium, and iron were virtually unchanged in the supernatant of variant culture experiments (P greater than 0.05). The level of manganese was higher in ethylenediaiene tetraacetic acid (EDTA), disodium salt treated cultures as compared to the control (P less than 0.05; n = 20).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1505421 TI - Thyroid hormone profiles in patients with chronic renal failure on conservative management and regular haemodialysis. AB - Patients with chronic non-thyroid illness (NTI) generally show biochemical features of hypothyroidism despite their being clinically euthyroid. Using assays that employ the antibody coated tubes technique, we measured thyroid hormone levels in 52 patients with chronic renal failure. 30 of the patients were on conservative management while 22 were on regular haemodialysis (HD) for a mean period of 14.2 +/- 9.9 months. The findings were compared to those of 14 healthy controls. All patients were clinically euthyroid. Only 3 patients on HD had goitres. The mean value of total thyroxine (TT4) total triiodo thyronine (TT3), free thyroxine (FT4) and the free triiodothyronine (FT3) were low in patients compared with controls (P less than 0.01). The mean basal thyroid stimulating hormone (TSH) levels were significantly higher in patients than in controls (P less than 0.001). There were no significant differences in all parameters between the patients on conservative management and those on haemodialysis (P greater than 0.05). Although all patients were clinically euthyroid, the biochemical features suggest hypothyroidism. PMID- 1505423 TI - Rehabilitation of the blind: a review. AB - Rehabilitation of the blind is an active process whereby the blind person is helped to become an independent and useful member of the community. Rehabilitation thus improves the psychological wellbeing of the blind person as well as making him a happy, contributing member of the society. PMID- 1505422 TI - Oral health habits and periodontal health among a group of university students in Kenya. AB - The purpose of this study was to determine the oral health habits and periodontal health among a group of university students in Kenya. The study comprised 243 randomly selected first year students, mean age 23 years, at the University of Nairobi. Questionnaire response showed that 39% of the participants had visited a dentist before, mainly for extraction. Sixteen per cent said they visited a dentist at least once a year and 96% said they brushed daily. Clinical examination was done in a room with natural daylight using the WHO criteria. Plaque was visible on 35% of the surfaces. 11% of gingival sites examined bled on probing. Only one participant had pocket depth greater than or equal to 4 mm. Supra- and sub-gingival calculus was recorded at 18% of index tooth surfaces. The study will be considered as a baseline for later studies on oral health trends in similar populations. PMID- 1505424 TI - Multiple sexually acquired diseases occurring concurrently in an HIV positive man: case report, diagnosis and management. AB - A case of an HIV positive man with multiple sexually acquired disease occurring concurrently is described. Risk behaviours that could have predisposed him to HIV infection are discussed. The factors which might have interacted to make the sexually acquired infections severe and difficult to treat are postulated. PMID- 1505425 TI - [Advanced training in the development of human resources. Contributions to a strategic planning methodology for human resources in health]. PMID- 1505426 TI - [Strategic planning in the development of health services in Chile]. PMID- 1505427 TI - [Critical analysis of health planning models in Latin America]. PMID- 1505428 TI - [Theoretical outline for the development of intersectorial action in health]. PMID- 1505429 TI - [Leadership in nursing: possibilities and trends]. PMID- 1505430 TI - [The system of principles of teaching, dialectic of instruction and education]. PMID- 1505431 TI - [Current situation and the future of veterinary medicine]. PMID- 1505432 TI - [The scholarship program as an instrument of technical cooperation and its contribution to the prioritization of necessities in human resources formation in health: the experience in Cuba]. PMID- 1505433 TI - [Formation of human resources in the area of medical teaching at the Faculty of Medicine of Ribeirao Preto, Universidade de Sao Paulo]. PMID- 1505434 TI - [A comparison of EEG mapping with and without visual artefact control in focal cerebral lesions]. AB - In 163 patients with focal cerebral lesions, 43 of them with completed stroke, 43 patients with TIA, 33 patients with ICH and 29 patients with malignant and 15 patients with benign tumors EEG mapping and CT was performed. The results of EEG mapping obtained using automated artifact detection were compared to those achieved by means of visual control of raw EEG. Furthermore the impact of long (850 +/- 250s) or short (32s) analysis time was studied. Eliminating artifacts by means of visual control of raw EEG significantly more positive results were obtained than using automated artifact detection. That was found in patients with as well as in patients without lesions in CT. In relation to etiology a significant difference was found only in cerebrovascular diseases but not in the other patients-groups. Corresponding results were found in 75% of the patients. The visual control provided additional lateralization especially in patients with CS (37%) and TIA (26%). A longer duration of analysed EEG epochs did not increase the number of focal changes in EEG mapping. PMID- 1505435 TI - [The value of EEG mapping in intracerebral hematomas]. AB - 33 patients with intracerebral hemorrhage were studied and the findings of EEG mapping, routine EEG and CT were compared. It could be shown, that the EEG mapping revealed in 6 patients additional focal changes corresponding with the clinical signs compared to conventional EEG. Identical results of EEG mapping and CT were found in 27 patients. In 5 patients the focal changes were localised contralateral to the hyperdense lesion in CT, and in 1 patient the EEG mapping failed to show any lateralisation. A negative intercorrelation between the size of the hematoma and the frequency, which revealed the focal signs in EEG mapping, could be shown. PMID- 1505436 TI - [The dependence of rapid voluntary contractions on the tremor phase in parkinsonism]. AB - Parkinsonian patients sometimes have problems to produce really fast motor responses. Often, these are significantly delayed in comparison to those of normal controls. In patients with tremor-at-rest, this delay might be induced by some attraction of the movement execution to the tremor oscillator, according to a hypothesis of Hallet et al. (1977). This study now examined the phase relationship between the on-going tremor and the onset of fast voluntary contractions in Parkinson's disease (PD), quantitatively. Five patients with prominent tremor-at-rest performed rapid isometric index finger abductions under self paced (SP) and reaction time (RT) conditions, and force and surface EMG signals from the FDI muscle were analyzed. In both conditions the SP and the RT, data showed that the onset of the contraction mostly occurs during the descending phase of the tremor oscillation and, accordingly, the phasic EMG burst synchronously with the tremor bursts confirming the above mentioned hypothesis. PMID- 1505437 TI - [Event-related negativity and alpha band desynchronization in motor reactions]. AB - The foreperiod of a motor reaction to an impending stimulus is accompanied by a slow negative wave of the event-related potential, the "contingent negative variation" (CNV), when the imperative stimulus follows at a fixed interval to a warning stimulus. Using similar experimental paradigms, an event-related desynchronization (ERD) in the alpha range occurs indicating cortical activation before and during motor acts. Both EEG-parameters were quantified for four subjects using the following experimental design: One second after a non informative warning signal (WS) a cue was presented that indicated by which hand the subject had to respond quickly after presentation of a reaction stimulus (RS); subjects were requested to respond by pressing a button with their left or right thumb. EEG-signals were recorded unipolarly from 17 electrodes. Average ERPs and ERD were computed for all electrode sites for trials with left and right hand movements, respectively, and topographically displayed in simultaneous amplitude and ERD-maps. CNV and ERD could be observed simultaneously over similar brain regions, namely central over the motor cortex, frontal with possible location over the supplementary motor area (SMA) and also covering the parietal region. While the CNV had a interindividually different and wide distribution, the ERD calculated for the upper alpha band mapped focally over the electrode sites C3 and C4 overlaying primary sensorimotor structures, with a contralateral dominance. In contrast to the negativity which is terminated following delivery of the response stimulus, the ERD persisted during the motor reaction showing a similar pattern some hundreds of milliseconds before and after movement onset.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1505438 TI - [Are cognitive processes in a phase relation with 40 Hz EEG?]. AB - A coherent EEG-rhythm occurring in the 40 Hz range has been shown to correlate with cognitive processes of attention in a large number of studies. We intended to evaluate whether this frequency is of specific functional significance, and whether it may represent a rhythm of excitability for cognitive processes. The model of a rhythm of excitability assumes the 40 Hz-EEG to be a timer and organizer for information processing. Event-related potentials of 12 healthy normal subjects were recorded in an experiment of attention (auditory click stimulation). In order to evaluate whether the phases of the 40 Hz-EEG represent a rhythm of excitability, responses to stimuli having similar phases at the beginning of the stimulus were selected and averaged. An effect of the different 40 Hz-phases could not be demonstrated on the amplitude and latency of N100 and P200, components of the event-related potential associated with information processing. These findings suggest that a possible timer for cognitive processes of attention is not linked to the phases of the 40 Hz-surface-EEG. PMID- 1505439 TI - [P300 and dementia: diagnostic relevance II]. AB - Recent research on the relationship between ERP-latencies and reduced information process capabilities with demented subjects has yielded divergent results. In the present study P300-latencies and RT are used in an attempt to differentiate between demented and nondemented subjects. Based on the "feature-integration theory" of Treisman an experiment was designed in order to investigate more complex cognitive processes. The results showed that both P300-latency and RT may be used as additional diagnostic indices for cognitive capability. PMID- 1505441 TI - [Acoustic evoked brainstem potentials--patterns of stimulus artefacts in irreversible coma]. AB - Brainstem auditory evoked potentials (BAEP) were performed in a total of 20 subjects (mean age 33.2 +/- 15.1 years; severe head injury in most cases) with the diagnosis of coma depasse. The control group consisted of 33 healthy volunteers (mean age 26.9 +/- 5.3 years). The presence, latency and amplitude of the single BAEP-components and the variations of the stimulus artifact were evaluated. The mean amplitudes of the stimulus artifact of the brain dead subjects were calculated (means +/- SD) to be 0.26 +/- 0.12 microV (control group: 0.11 +/- 0.03 microV). Pathological alterations of the mechanics of the inner ear as well as extracerebral changes in conductivity or stimulus related depolarization processes in extracerebral parts of the auditory system were taken into consideration to be possible reasons for this significant (p less than 0.001; t-test) difference. PMID- 1505440 TI - [The prognostic place of EEG in comparison with evoked potentials in severe hypoxic brain damage]. AB - This retrospective study comprises 34 patients, who died due to the cerebral damage caused by severe anoxia, who were assessed by EEG and AEP or SEP on the same day and in whom at least one of these electrophysiological methods indicated a fatal prognosis. EEG-findings identified 76% of patients with fatal outcome, whereas SEP reliably predicted the outcome in 93% of patients, who died of the cerebral anoxia. In some patients centrally acting drugs made EEG-based but not SEP-based prognosis impossible. In some cases of fatal brain damage, however, only the EEG-findings as opposed to SEP-findings predicted the fatal outcome. Thus the combined assessment by EEG and SEP appears to be optimal in the assessment of an early prognosis. The BAEP were of less prognostic value than the EEG. BAEP findings indicating a fatal outcome were to be found mainly in final clinical stages with loss of brainstem function, whereas EEG as well as SEP identified a considerable number of fatal cases in spite of comparably favourable clinical findings. The evaluation of early electrophysiological testing done within the first 3 days after the anoxic event results in an identical estimation of the prognostic significance of EEG versus BAEP- or SEP-findings, respectively. PMID- 1505442 TI - [Do encephalo-electric signals determine the pulse frequency in man?]. AB - One of the most interesting problems in EEG analysis is the question of the genuine generator of these biosignals. Each spontaneous EEG sampled by surface electrodes looks like a summary of stochastically distributed encephalo electrical events. But analysing these data depending of the time distance of ECG R-waves we found signals which contain the information about the occurrence of the next ECG R-wave. The results make dubious the discussion about the autonomic character of sinus excitation as the heart pacemaker. PMID- 1505443 TI - [Spatial distribution of the action potentials of the sural nerve]. AB - We investigated the spatial distribution of the sural nerve sensory nerve action potential (SNAP) in 25 healthy subjects between 21 and 50 years. Stimulation was achieved through surface electrodes at the lateral malleolus. Recordings were made 15-18 cm proximal to the site of the stimulation from different positions on a line perpendicular to the sural nerve using needle electrodes insulated except for the tip. The amplitude of the SNAP decreased on both sides of the potential of highest amplitude. 10 mm lateral to the potential of highest amplitude the mean amplitude was reduced to 55%. The latency of the first positive phase decreased within increasing distance from the largest SNAP. We explained this with different influence of more distal, earlier depolarized nerve segments on the locally generated SNAP. In 20 subjects we performed an additional recording using an uninsulated needle electrode that was placed 3-4 cm subcutaneously perpendicular to the sural nerve. The latency of the SNAP recorded in this way was similar to the latency of the largest SNAP using the insulated needle electrode; however, the amplitude was smaller by 19%. We recommend for clinical practice to use the uninsulated needle in case the SNAP is smaller than 4 microV. PMID- 1505444 TI - [The tibial evoked potential in healthy children and adolescents: normal values]. AB - The somatosensory evoked cortical potentials were investigated for 35 healthy children (17 boys, 18 girls) between 6 and 17. The stimulation of the N. tibialis was affected at the Malleolus medialis using surface electrodes; the derivation was likewise conducted according to the ten-twenty system using surface electrodes. Investigations carried out employing this methodology demonstrate that the SEP's of the N. tibialis from the N30 to the N70 are clearly measurable in the children. The N30, P40 and N50 could be presented with the smallest standard deviations and side differences. The latencies of N30 and P40 show significant dependencies on the height of the children. Influence of gender could be demonstrated more for the latency of the N30 in from of longer latencies in boys that in girls which were independent of body size. PMID- 1505445 TI - Remembrance: the discovery of the hypothalamic gonadotropin-releasing hormone pulse generator and of its physiological significance. PMID- 1505446 TI - Remembrance: calcitonin: discovery and early development. PMID- 1505447 TI - Effects of activin and follicle-stimulating hormone (FSH)-suppressing protein/follistatin on FSH receptors and differentiation of cultured rat granulosa cells. AB - The aim of this study was to investigate the actions of both activin and FSH suppressing protein (FSP)/follistatin either alone or in combination on FSH receptor number and on the responsiveness of granulosa cells to FSH and LH. Granulosa cells were harvested from diethylstilbestrol-treated immature Sprague Dawley rats and cultured 48 h in serum-free medium with or without treatment. Activin treatment alone (3-100 ng/ml) resulted in a 4-fold increase in FSH receptor number with no change in binding affinity. This effect of activin was inhibited 31% by FSP (100 ng/ml) treatment which alone had no effect on FSH receptor number. Treatment with activin (100 ng/ml) prevented FSH-induced down regulation of FSH receptor number, whereas at lower concentrations (3-30 ng/ml) activin enhanced down-regulation of FSH receptor number by 20% (P less than 0.05). In contrast, FSP alone prevented FSH-induced down-regulation by increasing FSH receptor number up to 40-50%. Pretreatment of granulosa cells with activin, but not FSP, for 24 h increased the responsiveness of cells to FSH (20 ng/ml) and LH (40 ng/ml) shown by increases in aromatase activity, progesterone, and immunoreactive inhibin production over and above control in a manner which depended upon activin doses. We conclude that 1) activin enhancement of FSH action on rat granulosa cells may be mediated in part via regulation of FSH receptor number, and 2) the effects of FSP on granulosa cells are likely to be due to its activin binding properties. PMID- 1505448 TI - Secretion and hormonal regulation of interleukin-6 production by mouse uterine stromal and polarized epithelial cells cultured in vitro. AB - Uterine stromal (USC) and uterine epithelial (UEC) cells were isolated from immature and mature mice to determine their ability to secrete interleukin-6 (IL 6) in response to ovarian steroids, IL-1 alpha, and soluble products produced by the heterologous cell type. In addition, the effect of IL-6 on embryo attachment and outgrowth in vitro was determined. UEC cultured on nitrocellulose filter inserts in a polarized manner secreted IL-6 with a 2.5- to 5-fold apical vs. basal preference, as determined by a B9 hybridoma cell proliferation assay and enzyme-linked immunosorbent assay. The hormonal status of animals at the time uteri were removed did not influence subsequent secretion of IL-6, as UEC isolated from immature, diestrous, and estrous stage mice exhibited both a similar amount and had a similar apical preference for secretion of IL-6. The addition of 17 beta-estradiol (E) to UEC cultures markedly inhibited total IL-6 secretion, but did not affect vectorial secretion. The inhibitory effect of E on IL-6 secretion by UEC was consistent with an apparent decrease in IL-6 transcript observed by a reverse transcriptase polymerase chain reaction assay. Other transcripts detected by this assay in UEC included IL-1 alpha, but not IL-1 beta or tumor necrosis factor-alpha. Secretion of IL-6 by UEC was not stimulated by IL 1 alpha, conditioned medium from USC, or coculture with USC. USC secreted IL-6, and while this also was inhibited by E, progesterone was more effective in this regard at physiological concentrations. In addition, there was a synergistic effect of E plus progesterone on inhibition of IL-6 secretion by USC. Secretion of IL-6 by USC was stimulated by IL-1 alpha, and coculture studies demonstrated the ability of UEC to stimulate a several-fold increase in IL-6 secretion by USC. The cytokine transcripts detected in USC cultures included IL-6 and IL-1 alpha, but not IL-1 beta. Transcripts for tumor necrosis factor-alpha were present in USC only after culture with IL-1 alpha. IL-6 added to blastocysts on laminin coated tissue culture wells resulted in a transient inhibition of the rate of blastocyst attachment and, to a greater extent, an inhibition of the rate of embryo outgrowth. In addition, IL-6 inhibited the size of embryo outgrowths at 24 and 48 h of culture.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1505449 TI - Central corticotropin-releasing hormone activates the sympathetic nervous system and reduces immune function: increased responsivity of the aged rat. AB - CRH acts within the brain to activate the sympathetic nervous system and reduce cellular immune function. To determine the effects of age on CRH-induced elevations of sympathetic activity and suppression of immunity, we examined the responses of plasma catecholamines, neuropeptide-Y (NPY), corticosterone, and splenic natural killer (NK) activity after microinjection of rat CRH (200 pmol) into the lateral ventricle of aged (24-month-old) Fischer 344 (F344) rats compared to those in young (4-month-old) F344 rats. Basal concentrations of plasma norepinephrine and NPY were higher in the aged than in the young animals. In addition, CRH produced a greater elevation of plasma levels of catecholamines and NPY, which persisted for a longer period of time in the aged rats compared to responses in the young animals. Splenic NK activity showed an age-related decrement at baseline, and CRH induced a further significant (P less than 0.01) reduction of lytic activity in the aged rats, but did not alter cytotoxicity in the young rats. Corticosterone basal levels and responses were similar in the aged and young rats. These results show an age-related increase in autonomic outflow and suppression of NK activity after central CRH administration. In aged animals, the central nervous system may have a role in abnormal regulation of sympathetic activity and suppression of natural cytotoxicity in vivo. PMID- 1505450 TI - Carboxypeptidase H processing and secretion in rat clonal beta-cell lines. AB - Carboxypeptidase H (CP-H, EC 3.4.17.10) removes C-terminal basic amino acids from insulin and many other peptide hormone intermediates in endocrine and neural tissues. CP-H was studied in two rat insulinoma-derived clonal beta-cell lines that were chosen in part because their profile of hormone production is restricted. Although RIN 1046-38 cells predominantly produce insulin and RIN 1046 44 cells contain no known polypeptide hormone, both cell lines contain comparable levels of CP-H. The distribution of CP-H in RIN cells differs from primary tissues since only 25% of cellular CP-H is soluble whereas approximately 75% is associated with the membrane fraction. Immunoblotting with both N- and C-terminal antibodies detects a single 54 kilodalton (kDa) band corresponding to the mature form of CP-H in soluble and membrane RIN cell extracts and incubation media. Pulse-chase analysis shows that a 56 kDa precursor is initially synthesized and rapidly processed to a mature 54 kDa form. Newly synthesized, mature CP-H is detectable in the media by 30 min. Approximately 50% is retained within cells after 3 h of incubation. Secretion of CP-H activity from both RIN cell types and insulin from 1046-38 cells is acutely stimulated by membrane depolarization with KCl and attenuated by 10 mM MgCl2. Dense core secretory vesicles characteristic of the regulated secretory pathway are evident on transmission electron microscopy of both RIN cell lines. Thus, mature CP-H exists primarily as a membrane-associated form in RIN cells, but all forms of CP-H, including soluble and secreted enzyme, retain an intact C-terminus. PMID- 1505451 TI - Insulin-like growth factor-I supports formation and activation of osteoclasts. AB - Although the action of insulin-like growth factor-I (IGF-I) on bone formation has been extensively investigated, the effect of the factor on bone resorption is little known. We first examined the effect of IGF-I on bone resorption by preexistent osteoclasts by using unfractionated bone cells cultured on dentin slices. IGF-I had a dose-related effect of stimulating bone resorption by preexistent osteoclasts, whereas IGF-II did not. When IGF-I was added to cultures of bone cells after preexistent osteoclasts had degenerated on the dentin slices, IGF-I increased the number of osteoclastic multinucleate cells (MNCs) with tartrate-resistant acid phosphatase activity. Moreover, IGF-I augmented the area of pits produced by newly formed osteoclasts. These results suggest that IGF-I directly or indirectly stimulates osteoclast recruitment and activation. Therefore, we next examined the direct effect of IGF-I on osteoclastic MNC formation by using hemopoietic blast cells. In the presence of 1,25 dihydroxyvitamin D3, IGF-I, like granulocyte-macrophage colony-stimulating factor (GM-CSF), dose-dependently increased the number of TRAP-positive MNCs. This stimulatory effect of IGF-I was additive with that of GM-CSF. Both IGF-I and GM CSF supported the survival of the blast cells, indicating that IGF-I as well as GM-CSF are supporting factors for osteoclast differentiation. In addition, the blast cells possessed high affinity binding sites for IGF-I, with a Kd of 0.8 nM. These data, thus, indicate that IGF-I stimulates osteoclastic bone resorption through its direct or indirect action of supporting the generation and activation of osteoclasts. PMID- 1505452 TI - Effect of vasotocin on cytosolic free calcium concentrations in frog adrenocortical cells in primary culture. AB - In a previous report we have shown that vasotocin (AVT), the amphibian counterpart of vasopressin, is a potent stimulator of corticosterone and aldosterone secretion by frog adrenocortical cells. We have also observed that the stimulatory effect of AVT on corticosteroid secretion is mediated through activation of receptors positively coupled to phospholipase-C. In the present study we examined the effect of AVT on cytosolic Ca2+ concentrations ([Ca2+]i). Since the interrenal (adrenal) gland of the frog is composed of a mixed population of chromaffin and adrenocortical cells, cytochemical identification of cultured cells was performed by immunofluorescence, using antibodies to AVT or 11 beta-hydroxylase as markers of chromaffin cells or steroid-producing cells, respectively. Cultured interrenal cells were loaded with the fluorescent Ca2+ indicator indo-1, and variations in [Ca2+]i were studied using dual emission wavelength microfluorimetry. Exposure of adrenocortical cells to AVT induced elevation of [Ca2+]i. Prolonged infusion of AVT caused an immediate increase in [Ca2+]i, followed by a sustained response of adrenocortical cells. Repeated pulses of AVT resulted in a gradual decline in the [Ca2+]i increase, suggesting the existence of a desensitization phenomenon. The effect of AVT on calcium mobilization was totally blocked when the cells were incubated in the presence of the V2 antagonist [d(CH2)5,D-Phe2,Ile4,Ala9-NH2]AVP. In calcium-free medium, the AVT-evoked increase in [Ca2+]i was suppressed. In contrast, when Ca2+ was replaced by Mn2+ in the incubation medium, the early response of the cells (transient peak of [Ca2+]i) was preserved, while the plateau phase disappeared. Incubation of the cells with the dihydropyridine Ca2+ channel blocker nifedipine did not affect the AVT-induced [Ca2+]i rise. These results indicate that AVT exerts a dual action on [Ca2+]i in frog adrenocortical cells. The initial rise of [Ca2+]i can be ascribed to immediate mobilization of intracellular Ca2+ stores, probably mediated by inositol trisphosphategated channels, whereas the sustained increase in [Ca2+]i results from nifedipine-insensitive plasma membrane Ca2+ channels. PMID- 1505453 TI - Superinduction of c-fos gene expression by estrogen in cultured guinea-pig endometrial cells requires priming by a cycloheximide-dependent mechanism. AB - The c-fos gene expression is rapidly induced by various mitogenic agents and protein synthesis inhibitors in many cell types. Estradiol-17 beta can induce c fos gene expression in breast cancer cell lines and in the uterus in vivo, but not in cultured guinea-pig endometrial cells. Using this model, we investigated whether a protein synthesis inhibitor, cycloheximide, could induce the c-fos gene and permit a superinduction by estrogens. In the presence of cycloheximide (10 micrograms/ml), protein synthesis was inhibited at 95% within the first hour. From 190 min after the addition of estradiol-17 beta or diethylstilbestrol (10( 8) M) and cycloheximide (10 micrograms/ml), there was a significant increase (ranging from 3- to 5-fold) of the c-fos messenger RNA level (2.2 kilobase in size), compared with the level in cells treated with cycloheximide alone. Nonestrogenic steroid hormones and estradiol-17 alpha were unable to induce c-fos gene expression in the presence of cycloheximide. The effect of estradiol-17 beta observed in the presence of cycloheximide was completely abolished by 4-hydroxy tamoxifen or by Ly 156758 or by ICI 164384 (10(-6) M). The c-fos mRNAs were rather stable in cells treated with cycloheximide for 2 h (half-life = 51 +/- 6 min) and there was no further increase in the c-fos messenger RNA stability after the addition of cycloheximide plus estradiol-17 beta (half-life = 40 +/- 3 min). The overall results suggest a response at the transcriptional level. In conclusion, cycloheximide transmits activating signals to the c-fos gene which act as priming elements to allow the estrogen action in cultured guinea-pig endometrial cells. PMID- 1505454 TI - Developmental changes in levels of luteinizing hormone receptor and androgen receptor in rat Leydig cells. AB - To further assess the hormonal response capabilities of Leydig cell progenitors (PLC) from 21-day-old rats, their levels of LH and androgen receptors (LH-R and AR) were measured and compared to those of isolated immature (ILC) and adult Leydig cells (ALC) from 35- and 90-day-old rats, respectively. Levels of LH receptor were estimated by Scatchard analysis of binding to [125I]hCG, and levels of LH receptor mRNA were determined by Northern blot analysis using a rat LH receptor antisense RNA probe. The numbers of LH receptors per cell measured by the binding study were 2,623 +/- 1,110 in PLC, 9,024 +/- 1,992 in ILC, and 39,896 +/- 15,234 in ALC (mean +/- SEM of four replicate experiments; ALC significantly greater than either PLC or ILC at P less than 0.05). The Northern blotting revealed three major bands [6.7, 2.6, and 2.3 kilobases (kb)] that were present in Leydig cells at all three ages and were not detected in HepG2 cells. When the steady state levels of the predominant 6.7-kb species were normalized to actin mRNA, PLC were 6.3-fold lower than ILC and 1.7-fold lower than ALC (n = 3 replicate isolations of poly(A) RNA). The 2.6- and 2.3-kb species exhibited similar trends. Levels of AR were estimated by immunoblotting using a polyclonal antibody against a synthetic peptide of the receptor (residues 14-32) that detected a 110-kilodalton AR protein. Levels of AR mRNA were estimated by Northern blot analysis, using a rat AR antisense RNA probe that detected a single 10-kb AR mRNA. The relative levels of AR protein were 1.0, 1.5, and 0.5 in PLC, ILC, and ALC, respectively (n = 3). Similar trends were observed for AR mRNA (n = 3). The observation that both LH and AR levels were lower in PLC compared to ILC is consistent with the hypothesis that the former are progenitors of Leydig cells. PMID- 1505455 TI - Characterization of 3T3-L1 storage lipid metabolism: effect of somatotropin and insulin on specific pathways. AB - TLC of total cellular lipids showed that 3T3-L1 cells predominantly accumulate triglycerides. GH and insulin principally regulated glucose utilization for synthesis of the fatty acid portion of 3T3-L1 triglycerides, with little effect on glucose utilization for synthesis of other lipids or triglyceride glycerol. Gas chromatographic mass spectrometry (MS) showed that 50% of 3T3-L1 triglyceride fatty acids are 16-carbon chains. However, 3T3-L1 adipocytes were unusual, in that 20% of their triglyceride fatty acids were C15 or C17 in length, observed by both MS of saponified triglycerides and electrospray MS of intact triglycerides. Gas chromatographic analysis of 14C-labeled fatty acids showed 3T3-L1 utilization of [14C]glucose for synthesis of C15 and C16 fatty acids. Insulin and GH regulated the amount of [14C]glucose incorporation into C15 and C16 fatty acids without altering their relative ratio. GH antagonized all studied insulin regulated events. GH antagonism of insulin-stimulated 3T3-L1 glucose transport, glucose oxidation, and glucose utilization for lipid synthesis reached a plateau of 50-60% inhibition at 0.1-0.2 nM. Insulin, at 0.1 nM, suppressed 3T3-L1 generation of glycerol from lipolysis by approximately 50%. GH, between 0.04-1.0 nM, fully reversed the insulin-inhibited lipolysis, although GH did not stimulate lipolysis beyond that in untreated control cultures. The results suggest that GH regulates a very early event in the insulin signal transduction pathway, such that is affects all insulin-responsive processes to essentially the same extent. PMID- 1505456 TI - Requirements of follicle structure for thyroid hormone synthesis; cytoskeletons and iodine metabolism in polarized monolayer cells on collagen gel and in double layered, follicle-forming cells. AB - Thyroid cells take up iodine and synthesize thyroid hormones. Thyroid cell polarity plays an important role in the uptake of iodine. However, we do not know whether polarity itself is enough for thyroid hormone synthesis or whether follicle structure is required for it. Using polarized monolayer porcine thyroid cells, cultured on collagen-coated filters, and double layered, follicle-forming cells, we analyzed the relationships of iodine metabolism and cell polarity (and follicle formation). We demonstrated that follicle structure was required for thyroid hormone synthesis. A quick-freezing and deep-etching method revealed the three-dimensional ultrastructures of cytoskeletons in the thyroid cells. On the collagen gel, the thyroid cells are reorganized into polarized monolayer cells; the basal cell membranes are in contact with the collagen gel and the apical ones face the culture medium. Actin microfilaments predominate under the apical cell membranes and intermediate filaments in the basal cytoplasm. The arrangement of these cytoskeletons determines the polarity of the cells. When the cells are cultured as double layers, follicle structures are reconstructed between the two monolayers. When apical cell membranes are in contact with other apical ones or when the cells are cultured as double layers, the cells are reorganized into follicles; the basal cell membranes are in contact with the collagen gel, and the apical ones face the follicle cavities. Actin microfilaments predominate at the apical cell membranes and intermediate filaments in the basal cytoplasm. Polarized thyroid cells transport iodine from the basal compartments to the apical ones, but cannot organify iodine into thyroid hormones. However, follicle forming cells, cultured as double layers, take up iodine and organify it into thyroid hormones. Polarity is important for iodine uptake, and follicle structure is required for thyroid hormone synthesis. PMID- 1505457 TI - Parathyroid hormone (PTH)-related protein, PTH, and 1,25-dihydroxyvitamin D in dogs with cancer-associated hypercalcemia. AB - Circulating N-terminal PTH-related protein (PTHrP), N-terminal PTH, and 1,25 dihydroxyvitamin D [1,25-(OH)2D] concentrations were measured in normal dogs and dogs with cancer-associated hypercalcemia (CAH), parathyroid adenomas, and miscellaneous tumors. PTHrP was undetectable (less than 1.8 pM) in normal dogs and increased in dogs with CAH due to adenocarcinomas derived from apocrine glands of the anal sac (44.9 +/- 27 pM), lymphoma (8.3 +/- 4.4 pM), and miscellaneous carcinomas (13.3 +/- 11.4 pM). The PTHrP concentration decreased in dogs with lymphoma and anal sac adenocarcinomas after successful treatment of CAH. The PTHrP concentration had a significant linear correlation with total serum calcium in dogs with anal sac adenocarcinomas and hypercalcemia, but not in dogs with lymphoma and hypercalcemia. Serum N-terminal PTH concentrations were usually in the normal range (12-34 pg/ml) for all groups of dogs except dogs with parathyroid adenomas (83 +/- 38 pg/ml). The serum PTH concentration increased after successful treatment of CAH. Serum 1,25-(OH)2D concentrations were decreased, normal, or increased in dogs with CAH, and 1,25-(OH)2D levels decreased after treatment of CAH. In summary, circulating concentrations of PTHrP are consistently increased in dogs with CAH, and PTHrP appears to play an important role in the induction of hypercalcemia. PMID- 1505458 TI - Cellular mechanism of metformin action involves glucose transporter translocation from an intracellular pool to the plasma membrane in L6 muscle cells. AB - The effects of the oral hypoglycemic drug metformin on glucose and amino acid transporter activity and subcellular localization of GLUT1 and GLUT4 glucose transporters were tested in cultured L6 myotubes. In muscle cells preexposed to maximal doses of metformin (2 mM, for 16 h), 2-deoxyglucose uptake was stimulated by over 2-fold from 5.9 +/- 0.3 to 13.3 +/- 0.5 pmol/min.mg protein. Uptake of the nonmetabolizable amino acid analog methylaminoisobutyrate was unaffected by treatment with the drug under identical conditions. Extracellular calcium was required to preserve the full response to the biguanide. Exposure of muscle cells to insulin in the presence of metformin resulted in further activation of 2 deoxyglucose transport. The latter effect was additive to the maximum effect of metformin, suggesting that the biguanide stimulates hexose uptake into muscle cells by an insulin-independent mechanism. Glucose transporter number quantified by performing studies of D-glucose-protectable binding of cytochalasin-B in plasma membranes (PM) and internal membranes (IM) prepared from L6 myotubes revealed that a 16-h treatment with 800 microM metformin significantly elevated glucose transporter number in the PM (by 47%), with an equivalent decrement in glucose transporter number (47%) in the IM. Western blot analysis using antisera reactive with the GLUT1 and GLUT4 isoforms of glucose transporters showed that metformin caused a reduction in GLUT1 content in the IM fraction and a concomitant increase in the PM. Unlike insulin, metformin treatment had no effect on the subcellular distribution of GLUT4. We propose that the molecular basis of metformin action in skeletal muscle involves the subcellular redistribution of GLUT1 proteins from an intracellular compartment to the plasma membrane. Such a recruitment process may form an integral part of the mechanism by which the drug stimulates glucose uptake (and utilization) in skeletal muscle and facilitates lowering of blood glucose in the management of type II diabetes. PMID- 1505459 TI - Mechanism of angiotensin II-induced proliferation in bovine adrenocortical cells. AB - The peptide hormone angiotensin-II (AII) is a potent vasoconstrictor and major regulator of aldosterone synthesis. In addition, AII also has growth-promoting effects. We have recently shown that the lipoxygenase (LO) pathway of arachidonic acid plays a major role in AII-induced aldosterone synthesis in adrenal glomerulosa cells. The LO pathway is also involved in the vasopressor and renin inhibitory effects of AII. However, the role of LO products in AII-induced mitogenic effects have not yet been investigated. In the present studies we have evaluated the role of the LO pathway in AII-induced proliferative responses in a bovine adrenocortical cell clone termed AC1 cells. In addition, the potential receptor type and mechanism of AII-induced proliferation was studied by evaluating the effect of specific nonpeptide type 1 and type 2 AII receptor antagonists and the role of protein kinase-C (PKC). AII-induced DNA synthesis was significantly attenuated by two structurally dissimilar LO inhibitors, baicalein and phenidone. In addition, the LO product 12-hydroxyeicosatetraenoic acid (12 HETE) itself caused a significant increase in DNA synthesis, suggesting that the 12-LO pathway in part plays a role in AII-mediated mitogenesis. AII-induced proliferative responses were blocked by the type 1 AII receptor antagonist. Both AII- and 12-HETE-induced increases in DNA synthesis were markedly inhibited by two PKC blockers, staurosporine and sangivamycin. Further, both AII and 12-HETE could activate PKC by translocating it from the cytosol to the membrane fraction, as determined by Western immunoblotting. These results suggest that both 12-LO activation and protein kinase-C have an important role in AII-induced adrenal cell proliferation. PMID- 1505460 TI - Constitutive expression of osteoclast-stimulating activity by normal clonal osteoblast-like cells: effects of parathyroid hormone and 1,25-dihydroxyvitamin D3. AB - Osteoblasts are known to produce osteoclast-stimulating activity (OSA). The aim of the current study was to relate the expression of OSA to the osteoblastic phenotype and examine its regulation by calciotropic hormones. The study was performed with the normal osteoblastic cell clone CRP 10/30 and the preosteoblastic clone CRP 4/7. OSA was determined with the well described isolated osteoclast pit assay, using sperm whale dentine as substrate. In contrast to previous studies, the assay was carried out at pH 7.36, rather than at pH 6.4 or 6.9. The results indicate that over 24 h, CRP 10/30 cells produce constitutively OSA, which compared to controls corresponds to an about 7-fold increase in resorption pits. There was considerably less activity expressed by either CRP 4/7 cells or fibroblasts. OSA proved to be heat labile, and its mol wt was estimated to be over 10 kilodaltons. While PTH-(1-34) did not influence the synthesis of OSA, the number of pits formed by osteoclasts incubated with medium conditioned by 1,25-dihydroxyvitamin D3 [1,25-(OH)2D3]-treated CRP 10/30 cells was increased 3-fold above baseline values. A similar increase was obtained with 1.25-(OH)2D3 added directly to CRP 10/30-conditioned medium. These results could not be duplicated with 1,25-(OH)2D3 added to either control medium or medium conditioned by CRP 4/7 cells or fibroblasts. The present study shows that normal clonal bone cells synthesize constitutively OSA, which is not regulated by PTH or 1,25-(OH)2D3. Furthermore, the results suggest that the synthesis of bone cell derived OSA is limited to cells expressing the mature osteoblastic phenotype. Finally, CRP 10/30-conditioned medium appears to permit 1,25-(OH)2D3 to function on osteoclasts. PMID- 1505461 TI - Biological mimicry of gonadotropin action by antiidiotypic antibodies to luteinizing hormone: characterization and biological properties. AB - High affinity polyclonal rabbit antibodies to ovine (o) pituitary LH [anti-oLH immunoglobulin G (IgG) Ab1] were used to immunize young Southdown lambs. Their serum samples as well as those from controls receiving normal rabbit IgG were studied for the presence of anti-Ab1 antibodies. In RIAs using [125I]oLH and affinity-purified Ab1, sera from experimental sheep showed high activity, as expressed in oLH equivalents. These sera also showed ability to compete with [125I]oLH for binding to receptor on pig ovarian and testicular membranes. The antiidiotypic antibodies (Ab2) in experimental sheep sera were purified by successive affinity chromatography on immobilized rabbit normal IgG and immobilized oLH-IgG columns. Ab2-IgG eluted from the latter mimicked oLH in RIAs and RRAs. These purified Ab2 antibodies were also of a stimulatory type, because they elicited progesterone production in rat granulosa cells and collagenase dispersed rat Leydig cells. This stimulatory action was counteracted by coincubation with anti-oLH-IgG, which would also terminate (oLH) hormone action in a similar manner. The Ab2 antibodies had no effect on oFSH RIA or on the binding of [125I]oFSH to pig ovarian receptors, indicating specificity with respect to LH antigenic structure and function. As can be expected from the choice of the immunogen (polyclonal anti-oLH-IgG), only a small percentage of the true Ab2 population could display biological mimicry of the original antigen (oLH). Their presence in circulation during 6-8 months had no effect on testicular size or body growth. The formation of Ab2 antibodies to rabbit anti oLH-IgG was also demonstrated in male rats, but these were not purified. In this instance also there was no effect on testicular weight after 6 months of immunization. These results show the feasibility of producing antiidiotypic antibodies that stimulate gonadal function in a manner much like the pituitary gonadotropin (oLH). PMID- 1505463 TI - Thyrotropin-releasing hormone and lysine-bradykinin stimulate arachidonate liberation from rat anterior pituitary cells through different mechanisms. AB - TRH and lysine-bradykinin (Lys-bradykinin) increase PRL release and arachidonate liberation from anterior pituitary cells. We investigated whether the arachidonate liberation stimulated by TRH and Lys-bradykinin originates in pituitary lactotropes and whether these events are accomplished through similar mechanisms. Lys-bradykinin and TRH rapidly (0.5 min) increased the intracellular [3H]arachidonate content of rat anterior pituitary cells. Lys-bradykinin also increased [3H]arachidonate liberation and PRL release from lactotrope-enriched pituitary cells, but not from a pituitary cell preparation with a diminished number of lactotropes. In contrast, TRH increased [3H]arachidonate liberation from both lactotrope-enriched and lactotrope-diminished preparations; this increased [3H]arachidonate liberation stimulated by TRH in the lactotrope diminished cells may originate in the thyrotropes. The effects of TRH and Lys bradykinin on [3H]arachidonate and [14C]stearate liberation in perfused pituitary cells also were determined. Both secretagogues increased arachidonate and stearate liberation in a biphasic manner, characterized by a transient spike, followed by a lower magnitude wave of fatty acid release. The spike phase produced by Lys-bradykinin was more pronounced than that produced by TRH. The calcium dependence of TRH- and Lys-bradykinin-stimulated arachidonate liberation also was investigated. Cobalt and the low calcium medium containing ionomycin were used to block the secretagogue-induced increase in intracellular calcium concentrations. These conditions blocked TRH-stimulated arachidonate liberation, but only marginally decreased Lys-bradykinin-stimulated arachidonate liberation, indicating that the two peptides act through different mechanisms. Therefore, TRH stimulation of arachidonate liberation is linked to an increase in intracellular calcium. In contrast, Lys-bradykinin increases arachidonate liberation through a calcium-independent intracellular mediator. This calcium-independent increase in arachidonate liberation may involve the bradykinin receptor being coupled directly to a phospholipase, a G-protein that provides a link between the bradykinin receptor and the phospholipases that liberate arachidonate, or bradykinin-induced activation of a protein kinase-C that activates the phospholipases and subsequently liberates arachidonate. PMID- 1505462 TI - Rat melanin-concentrating hormone messenger ribonucleic acid expression: marked changes during development and after stress and glucocorticoid stimuli. AB - Melanin-concentrating hormone (MCH) is a cyclic neuropeptide first isolated from fish and rats. MCH may be involved in the control of the hypothalamic-pituitary adrenocortical axis and, more generally, of specific goal-oriented behaviors and homeostatic functions in mammals. In this paper we examine 1) the cellular distribution of MCH gene transcripts in the rat central nervous system, 2) the changes in neuronal expression of MCH mRNA during rat development, and 3) the effects of stress and hormonal stimuli on rat MCH (rMCH) gene activity. Northern blot analysis and in situ hybridization histochemistry show that mature rMCH mRNA (1.0 kilobase) is very abundant in the zona incerta and the dorsolateral hypothalamus. While this is in agreement with previous peptide mapping by immunohistochemical techniques, a surprising new result is that a few clusters of rMCH mRNA-containing cells are found outside the hypothalamus, in the olfactory tubercle and the pontine tegmentum. Developmentally, rMCH mRNA is detected on embryonic day 18; its level increases gradually during early postnatal life and rises abruptly at weaning to reach a constant value in adult rats. In addition, striking variations in rMCH mRNA length occur during postnatal development and are found to be variations in the polyadenylate tail. Interestingly, this structural modification appears to be independent of the increase in rMCH mRNA levels. The regulation of rMCH mRNA expression by glucocorticoids and chronic stress is examined by Northern blot analysis. Chronic intermittent footshock stress causes a 58% or 29% decrease in rMCH mRNA content in the whole hypothalamus after a 1- or 3-day regimen, respectively. In contrast, the rMCH mRNA level returns to normal after a 7-day regimen. Two weeks after adrenalectomy (ADX) the whole hypothalamus rMCH mRNA content decreases 2.5-fold, but rises close to the control value 3 weeks after ADX. Dexamethasone administration 2 weeks after ADX not only reverses the fall in rMCH mRNA, it even provokes a slight increase (123% of control). No change in rMCH mRNA length is observed after chronic stress or ADX and dexamethasone injection. These results provide evidence for a negative regulation of rMCH gene expression by stress and suggest a major role for glucocorticoids in a positive feedback control of rMCH gene activity. PMID- 1505464 TI - Cellular localization and characterization of Glut 3 glucose transporter isoform in human brain. AB - In the present study we examined the expression and localization of Glut 3 in human brain using peptide-specific antisera. Glut 3 was expressed at 2-3 times higher levels in cerebral cortex from adult (n = 6) compared to that from neonatal infants (n = 4; P less than 0.05). However, similar levels of immunoreactive Glut 3 were present in cerebellum from adults (n = 6) and newborns (n = 4). Cellular localization of Glut 3 in adult (n = 5) and neonatal (n = 5) infant brains was undertaken by immunohistochemical analysis. Glut 3 was visible in the adult neuropil of the cerebral cortex; in certain cellular processes within the deeper cortical layers; in intravascular white cells, including monocytes, lymphocytes and granulocytes; and in microvascular endothelial cells. Neither the premature nor the mature newborn cerebral cortex exhibited Glut 3 labeling in the neuropil or microvasculature. In the cerebellum, given the stratified nature of the cellular arrangement, Glut 3 was more clearly and definitively noted in the cellular processes at all stages of development. Double labeling studies using neuronal (neurofilament) and astrocytic (glial fibrillary acidic protein) markers indicated that Glut 3 was primarily expressed in neurons. We conclude that Glut 3 is localized in many cellular components, including white blood cells in human brain. The prominent localization of Glut 3 to mature neuronal processes suggests an essential role for this transporter in regulating fuel requirements for dendritic and axonal traffic, thereby mediating neurotransmission. Further study is required to address the possibility that another as yet undefined glucose transporter isoform is expressed in other cell specific regions of the brain. PMID- 1505465 TI - A new, nongenomic estrogen action: the rapid release of intracellular calcium. AB - We have investigated the effects of steroids on the intracellular calcium ion concentration [Ca2+]i in chicken granulosa cells obtained from the two largest preovulatory follicles of laying hens. [Ca2+]i was measured in cells loaded with the Ca(2+)-responsive fluorescent dye fura-2. The resting [Ca2+]i in these cells was 100 +/- 5 nM. There was an immediate (i.e. less than 5 sec) 4- to 8-fold increase in [Ca2+]i in all of the 76 cells examined after the addition of 10(-7) M estradiol-17 bdta. Estradiol-17 beta was effective between 10(-10)-10(-6) M. Estradiol-17 alpha, estrone, and estriol (10(-8)-10(-6) M) were as effective as estradiol-17 beta, but the progestins, pregnenolone, and progesterone, and the androgens, testosterone, androstenedione, or 5 alpha-dihydrotestosterone were ineffective at concentrations up to 10(-5) M. The prompt estradiol-17 beta induced [Ca2+]i spike was not affected by incubating the cells in Ca(2+)-free medium containing 2 mM EGTA or by pretreating them with the Ca2+ channel blockers lanthanum (1 mM), cobalt (5 mM), methoxyverapamil (D600; 50 microM), or nifedipine (20 microM). The estrogen-triggered [Ca2+]i surge was also not affected by pretreating the cells with the conventional estrogen receptor antagonist tamoxifen (10(-5) M), or the RNA and protein synthesis inhibitors actinomycin D (1 microgram/ml) and cycloheximide (1 microgram/ml), but was abolished by pretreating the cells with inhibitors of inositol phospholipid hydrolysis, neomycin (1.5 mM) and U-73,122 (2.5 microM). The closely related, but inactive, compound U-73,343 (1 microM) did not affect the estrogen-triggered [Ca2+]i surge. Estradiol-17 beta (10(-7) M), but not progesterone (10(-5) M), also triggered a large [Ca2+]i surge in pig granulosa cells, which, like the [Ca2+]i surge in chicken granulosa cells, was almost immediate, transient, and unaffected by incubation in Ca(2+)-free medium or pretreatment with methoxyverapamil (D600; 50 microM), lanthanum (1 mM), or tamoxifen (10(-5)M). However, granulosa cells from immature rats primed with diethylstilbestrol or PMSG did not respond to estradiol-17 beta, even at concentrations as high as 10( 5) M, although they promptly generated a [Ca2+]i transient upon exposure to LHRH (10(-5) M). These results suggest that estrogens almost instantaneously trigger the release of Ca2+ from intracellular stores which may be mediated through phosphoinositide breakdown. The striking rapidity of this estrogen-induced internal Ca2+ mobilization is consistent with the activation of a cell surface receptor which is different from the conventional slowly acting, gene-stimulating nuclear estrogen receptor. PMID- 1505466 TI - Identification of nuclear triiodothyronine receptors in the thymic epithelium. AB - Thymic epithelial cell physiology is known to be under neuroendocrine control. In particular, thyroid hormones modulate thymic hormone secretion by thymic epithelial cells in vivo and in vitro, thus suggesting the existence of specific receptors for those hormones in this component of the thymic microenvironment. Yet, thyroid hormone-binding sites have previously been detected only in crude thymus fractions and lymphocytes. We, thus, decided to search for T3 receptors in the thymic epithelium, by using an antinuclear T3 receptor monoclonal antibody. In situ immunohistochemical analysis of thymic frozen sections showed nuclear labeling of both lymphoid and nonlymphoid cells in the cortex and medulla. Moreover, in vitro studies using thymic epithelial cell lines and the so-called thymic nurse cells revealed a positive reaction in the chromatin, with nucleoli remaining negative. Immunoblot data clearly showed a single protein band of 57K reactive with the antinuclear T3 receptor antibody in murine thymus extracts as well as in the thymic epithelial cell lines. Lastly, in vitro treatment of these cells with T3 resulted in a transient, yet profound, down-modulation of the receptor. In conclusion, our findings provide molecular evidence that the action of thyroid hormones on thymic epithelium occurs via the typical 57K nuclear T3 receptors. PMID- 1505467 TI - Effect of placement of dexamethasone adjacent to the ovine fetal paraventricular nucleus on adrenocortical steroid hydroxylase messenger ribonucleic acid. AB - The preterm rise in the concentration of ovine fetal plasma cortisol that initiates the events of parturition in sheep commences at approximately 125 days of gestational age (dGA; term = approximately 147 dGA). Concurrent with the rise in fetal plasma cortisol, adrenocortical steroid hydroxylase enzyme activity increases. The purpose of this study was 1) to quantitate changes in levels of mRNA for the steroid hydroxylases, 17-hydroxylase cytochrome P450 (P450(17)alpha), side-chain cleavage cytochrome P450 (P450scc), 11 beta hydroxylase cytochrome P450 (P450(11)beta), and C21-hydroxylase cytochrome P450 (P450C21); and 2) examine the role of the fetal paraventricular nucleus (PVN) in the onset of adrenocortical steroid hydroxylase mRNA expression. Unperturbed fetuses were collected by cesarian section under halothane anesthesia at 105 (n = 4), 120 (n = 4), 126-128 (n = 4), and 136 dGA (n = 3); neonatal animals were collected within 2 h after birth. To examine the role of the fetal PVN in regulation of adrenocortical steroid hydroxylase mRNA expression, ovine fetuses were stereotaxically implanted bilaterally 2 mm lateral to the fetal PVN at 105 107 dGA with either cholesterol (n = 4) or dexamethasone (DEX; n = 3). Implanted fetuses were collected by cesarian section under halothane anesthesia at 126-128 dGA. mRNA for both cytochrome P450(17)alpha and P450scc declined 3-fold from 105 to 120 dGA (P less than or equal to 0.05), and then increased by 126-128 dGA compared to that on 120 dGA (P less than or equal to 0.05) and continued to increase through term. Cytochrome P450C21 increased at 126-128 dGA compared to that on 105 and 120 dGA (P less than or equal to 0.05) and remained elevated through term. Three distinct transcripts [approximately 6.2, 4.2, and 2.5 kilobases (kb)] were observed for cytochrome P450(11)beta; the 4.2-kb transcript was predominant. While total message for P450(11)beta declined over increasing gestational age, no differences were noted for the 4.2-kb transcript until after birth, when levels significantly declined (P less than or equal to 0.025). Placement of DEX adjacent to the fetal PVN prevented reemergence of expression of mRNA for P450(17)alpha and P450scc at 126-128 dGA, but had no effect on mRNA for P450C21 or P45011 beta. We conclude that mRNA for P450(17)alpha and P450scc undergoes a decline in expression concurrent with the previously described period of adrenal hyporesponsiveness from 105-126 dGA, followed by an increase in mRNA that accompanies the preterm rise in fetal plasma cortisol.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1505468 TI - Hypercortisolemia inhibits yohimbine-induced release of norepinephrine in the posterolateral hypothalamus of conscious rats. AB - Chronic hypercortisolemia attenuates yohimbine (YOH)-induced increments in plasma levels of the sympathetic neurotransmitter norepinephrine (NE). The present study used in vivo microdialysis to study the effects of hypercortisolemia on YOH induced release of NE in the brain. Cortisol (25 mg/kg.day) or saline was infused sc into rats for 7 days via an osmotic minipump. Microdialysate and plasma concentrations of NE and its metabolites dihydroxyphenylglycol and methoxyhydroxyphenylglycol were measured before and after YOH (1 mg/kg, iv) administration in conscious animals, with microdialysate and plasma collections beginning 20-24 h after probe implantation. Chronic cortisol treatment resulted in attenuated NE, dihydroxyphenylglycol, and methoxyhydroxyphenylglycol responses in both microdialysate and plasma. The results indicate that YOH increases central neural as well as peripheral release, reuptake, turnover, and metabolism of NE and that hypercortisolemia suppresses these responses. PMID- 1505469 TI - Elevated levels of endogenous pregnenolone fatty acid esters in follicular fluid high density lipoproteins support progesterone synthesis in porcine granulosa cells. AB - Fatty acid esters of pregnenolone (PREG-FA) are present at high levels within ovarian follicular fluid (FF), although no physiological function has yet been attributed to these pregnenolone metabolites. We demonstrate in the following study that PREG-FA are predominantly localized in association with high density lipoproteins (HDL) within FF at levels that surpass those found in plasma HDL by approximately 200-fold. Extensive treatment with dextran-coated charcoal revealed that although nonconjugated steroids could be removed very efficiently from whole fluid and HDL, little effect could be demonstrated on the PREG-FA levels present within the fluid or its HDL component. This observed resistance to charcoal stripping may reflect a steroid-protein interaction that is altogether different from the non-conjugated steroid-protein association. Both plasma and FF-derived HDL were equally effective in supporting PROG biosynthesis in porcine granulosa cell cultures under normal culture conditions, but when PROG synthesis was dramatically blocked by inhibiting the P450 side-chain cleavage enzyme complex with the P450 enzyme inhibitor ketoconazole, only HDL of FF origin was capable of restoring PROG synthesis. Similar cultures that received HDL of plasma origin, containing similar levels of total cholesterol but far less PREG-FA, showed no significant difference in PROG accumulation over control cultures under these conditions. Several reports have described the presence of an entity within FF that was shown to resist charcoal stripping and enhanced PROG synthesis in granulosa cell cultures. Our data suggest that this entity within FF may indeed be the high levels of endogenous PREG-FA. We, therefore, propose a role for PREG FA as a potential substrate in the biosynthesis of PROG in porcine granulosa cells. PMID- 1505470 TI - Dynamic regulation of follicle-stimulating hormone-beta messenger ribonucleic acid levels by activin and gonadotropin-releasing hormone in perifused rat pituitary cells. AB - Maintenance of FSH biosynthesis requires ongoing exposure to pulsatile GnRH. Recent data demonstrate that activin also stimulates FSH biosynthesis. We used a perifused pituitary system to examine regulation of FSH beta mRNA levels by pulsatile GnRH and activin. Hourly pulses of 10 nM GnRH increased FSH beta mRNA levels by 3-fold. In the same experiment, continuous infusion of 50 ng/ml activin elicited a 50-fold increase in FSH beta mRNA. This magnitude of response to activin in perifusion was unexpected, as only a 2.7-fold increase in FSH beta mRNA was observed when activin was administered to pituitary cells that were cultured in dishes. Since perifusion columns, unlike culture dishes, are exposed to a continuous supply of fresh medium, we examined the possibility that endogenous factors produced by pituitary cells cultured in dishes were stimulating the cells in a paracrine fashion, thereby precluding the full response to exogenously added activin. The kinetics of FSH beta mRNA expression were examined immediately after pituitary dispersion and at different times after culturing the cells in plates. FSH beta mRNA levels fell rapidly after dispersion to 8% of initial levels and remained low over 8 h. Thereafter, FSH beta mRNA levels increased slowly and exceeded initial levels by the second day of culture. In a parallel set of experiments, when medium conditioned by exposure to plated cells was applied to the perifusion system, FSH beta mRNA levels were selectively stimulated (6-fold). These data suggest the removal during dispersion and subsequent accumulation in culture of pituitary-derived factors that are important for the maintenance of FSH beta mRNA levels. We conclude that activin plays a greater role in the regulation of FSH beta mRNA levels than was suggested by previous experiments employing static culture systems in which autocrine or paracrine stimulation may have obscured the effects of exogenously added activin. PMID- 1505471 TI - Sexual dimorphism in regulation of type II corticosteroid receptor immunoreactivity in the rat hippocampus. AB - To determine whether there are sex differences in the distribution of type II corticosteroid receptor-immunoreactive (type II-ir) cells in the rat hippocampus, we carried out a quantitative morphometric immunocytochemical study using a mouse monoclonal antibody, BUGR2. We report that in adrenally intact male and female rats, high densities of cells with nuclear type II-ir were observed in the pyramidal layer of field CA1 and the granular layer of the dentate gyrus. In intact males very few cells, presumably glia, in the stratum oriens showed type II-ir. In contrast, in females, interneurons with diffuse or cytoplasmic type II ir were observed in the stratum oriens of CA1 and CA3. There were also sex differences in the regulation of type II-ir by corticosterone, the predominant glucocorticoid, and female sex steroids. In male rats the density of cells with nuclear type II-ir in all parts of Ammon's horn and the dentate gyrus was decreased significantly after adrenalectomy (adx). In contrast, in females such reductions were observed only in the pyramidal layer of CA1 and the granular layer of the dentate gyrus. In both sexes, cells with intense diffuse or mainly cytoplasmic type II-ir were observed in the pyramidal layer and stratum oriens after adx. The loss of nuclear type II-ir in the hippocampus of adx females was not affected significantly by ovariectomy. In adx males, nuclear Type II-ir was restored in CA1 and the dentate gyrus after treatment with corticosterone or progesterone. Cells in CA3 were, however, unresponsive to treatment with either hormone. In contrast, in adx females, treatment with either corticosterone or progesterone restored nuclear type II-ir to cells in all regions of the hippocampus. In both adx males and females, cytoplasmic type II-ir observed in some cells in the pyramidal layer and stratum oriens, was abolished completely by corticosterone, and partially by progesterone treatment. In both adx males and females, estradiol treatment did not affect significantly the pattern of type II ir. Sex differences in the distribution of type II-ir interneurons in intact rats and the regulation of the intracellular location of type II-ir of adx rats by corticosterone and progesterone, may be important determinants of sex differences in the modulation of hippocampal function by glucocorticoids. PMID- 1505472 TI - Increases in cellular sodium concentration by arginine vasopressin and endothelin in cultured rat glomerular mesangial cells. AB - The present study was undertaken to determine whether arginine vasopressin (AVP), angiotensin-II, and endothelin (ET) increase the cellular sodium concentration ([Na+]i) in cultured rat glomerular mesangial cells. [Na+]i was measured using the fluorescence indicator dye sodium-binding benzofuran isophthalate. These three vasoconstrictor hormones increased cellular free calcium ([Ca2+]i) and [Na+]i in a dose-dependent manner ([Na+]i: basal, 11.5; 10(-7) M AVP, 20.5; 10( 7) M angiotensin-II, 13.8; and 10(-7) M ET, 21.2 mM). The mobilization of [Ca2+]i was faster than that of [Na+]i. The AVP-induced increase in [Na+]i was completely blunted by the potent V1 antagonist d(CH2)5Tyr(Me)AVP. Vasoconstrictor hormones produced a biphasic cellular pH (pHi) change, characterized by a transient acidification, followed by a sustained alkalinization. The Ca(2+)-free condition markedly reduced AVP- and ET-induced increases in [Ca2+]i and [Na+]i and biphasic changes in pHi. In the Na(+)-free state, the hormonally mobilized [Ca2+]i was significantly enhanced. Basal [Na+]i decreased to below 3 mM, and there was little increase in [Na+]i after the addition of vasoconstrictor hormones, suggesting that the source of [Na+]i is extracellular space. Only early acidification was obtained in the absence of a sustained alkalinization. The [Na+]i mobilization was closely related to the biphasic change in pHi. These results indicate that AVP, ET, and angiotensin-II increase [Na+]i in glomerular mesangial cells, and that the early mobilization of [Na+]i depends on Na+/Ca2+ exchange, and the sustained phase depends on Na+/H+ exchange. The hormonally mobilized [Ca2+]i is essential for the activation of Na+/H+ exchange, and an increase in [Na+]i is suggested to play an important role in cellular alkalinization. PMID- 1505473 TI - Calcium homeostasis in growth hormone (GH)-secreting adenoma cells: effect of GH releasing factor. AB - Human GH-secreting tumors are heterogenous regarding their basal secretory activity and response to GH-releasing factor (GRF). We have investigated whether such different secretory properties could be accounted for by alterations of intracellular mechanisms occurring at the calcium level. Basal free intracellular calcium concentrations ([Ca2+]i) and Ca2+ responses to GRF were studied in single cells cultured from fragments of five GH-secreting pituitary adenomas. We used the microspectrofluorimetric method and indo-1 as the fluorescent probe. The cell populations cultured from the tumors of patients A and C showed increased hormone secretion in response to GRF in vitro, whereas cultures from patients B, D, and E were unresponsive to the peptide. Basal [Ca2+]i measured in the five cell populations ranged from 82 +/- 18 to 118 +/- 27 nM. A 10-sec application of 10 nM GRF induced an increase in [Ca2+]i in 60% and 54% of A and C cells, respectively. In the nonresponsive cell populations, the number of calcium responses to GRF was lower, 26% (B cells), 5% (D cells), and 10% (E cells). Two principal responses types were observed: 1) an initial increase in [Ca2+]i, followed by a sustained plateau phase lasting for more than 200 sec; and 2) a monophasic peak of increased [Ca2+]i lasting approximately 1 min before returning to baseline levels. GRF responses were totally suppressed in the absence of Ca2+ ions in the external medium. Sixteen to 30% of the cells cultured from four of the five tumors showed spontaneous fluctuations of [Ca2+]i. These spontaneous Ca2+ transients were suppressed in Ca(2+)-free medium. The number of cells exhibiting such Ca2+ transients decreased with time in culture. Basal hormone secretion was higher in cultures from patient D, in which no spontaneous Ca2+ transients were observed in any of the 72 studied cells, and in cultures from patients E, in which only 16% of cells were spontaneously active. We conclude that 1) in human responsive somatotrophs, the involvement of Ca2+ in GRF stimulus-secretion coupling mechanisms is apparently similar to that described in somatotrophs of other species; 2) the lack of a secretory response to GRF observed in some tumors may result from impairment of Ca2+ responsiveness in either cell recruitment or response amplitude and/or duration; and 3) spontaneous rhythmic Ca2+ activity is apparently dissociated from basal hormone secretion in some of these tumor cells. PMID- 1505474 TI - Characterization of angiotensin-II receptor subtype on bovine thecal cells and its regulation by luteinizing hormone. AB - In this study the primary objectives were to localize angiotensin-II (AII) receptors on specific ovarian cells and determine whether these receptors are regulated by LH. AII receptor analysis, carried out using membrane fractions prepared from isolated thecal, granulosa, and luteal cells from bovine ovary, revealed that [125I]AII-binding sites were present only on thecal cells. The Kd and binding capacity were determined to be 0.29 +/- 0.08 nM and 66.9 +/- 8.1 fmol/mg membrane protein (mean +/- SEM from three experiments, each with duplicate determinations), respectively. None of the peptides unrelated to AII affected the binding of [125I]AII. Unlabeled AII, saralasin, and AIII were equipotent (IC50, approximately 5 nM for all three peptides) in competing with the radioligand. However, the binding affinity for AI was less by almost 2 log units. Using AII receptor subtype-specific nonpeptide antagonists, Losartan [a selective antagonist for the type 1 AII (AT1) receptor] and PD 123319 [a selective antagonist for the type 2 AII (AT2) receptor], AII receptors on thecal cells could be classified pharmacologically as AT2-type receptors. The IC50 determined from the competitive binding inhibition experiments for the various unlabeled competing substances were 5 nM, 20 nM, 200 nM, and 200 microM with respect to AII, p-amino-phenylalanine-AII, PD123319, and Losartan, respectively. Thecal cells cultured in a serum-free medium also expressed AII receptors, which could be up-regulated by LH or 8-bromo-cAMP in a dose-dependent manner. The number of AII receptors on thecal cells nearly doubled when the cells were cultured in the presence of 100 ng/ml LH, with little change in their Kd value. This increase in the number of AII receptors was inhibitable by a protein synthesis inhibitor, cycloheximide. In summary, we have demonstrated that in the bovine ovary, AII receptors belonging to AT2 subclass are predominantly expressed on thecal cells, and these receptors can be up-regulated by LH via a cAMP dependent mechanism. Thus, the bovine thecal cells in primary culture can potentially become a useful in vitro system to study the mechanism of regulation of AII receptor induction as well as the so far unknown function of this class of receptor. PMID- 1505475 TI - Increased plasma concentrations, hypothalamic content, and in vitro release of arginine vasopressin in inflammatory disease-prone, hypothalamic corticotropin releasing hormone-deficient Lewis rats. AB - The susceptibility of Lewis (LEW/N) rats to severe inflammatory disease has been causally associated with subnormal responsiveness of their hypothalamic CRH secreting neurons and, consequently, their hypothalamic-pituitary-adrenal axis to several stimulatory neurotransmitters and inflammatory cytokines. In the present study we investigated in this strain the secretory dynamics of another major activator of pituitary ACTH secretion, arginine vasopressin (AVP). To accomplish this, we evaluated the circadian plasma concentrations and circadian and glucocorticoid-induced changes in hypothalamic content and in vitro release of AVP in 8- to 10-week-old female LEW/N rats and compared these measurements to those obtained in parallel from age- and sex-matched histocompatible, inflammatory disease-resistant Fischer (F344/N) rats. Plasma concentrations and hypothalamic content and in vitro release of AVP were significantly elevated in LEW/N compared to F344/N rats in both the morning and evening. These indices of higher AVP secretion in LEW/N than in F344/N rats were also present after chronic dexamethasone treatment. These findings suggest increased AVP production and release in LEW/N rats, perhaps representing an adaptive compensation for insufficient CRH and glucocorticoid secretion. The high levels of circulating AVP might contribute to the excessive inflammatory responses of these animals. PMID- 1505476 TI - Carbohydrate structures of beta-core fragments of human chorionic gonadotropin isolated from a pregnant individual. PMID- 1505477 TI - Lactoferrin expression in the mouse reproductive tract during the natural estrous cycle: correlation with circulating estradiol and progesterone. AB - Lactoferrin (LTF), an iron-binding glycoprotein present in most exocrine secretions and in the secondary granules of polymorphonuclear leucocytes (PMN), is regulated by estrogen in the mouse reproductive tract. We investigated the expression of LTF mRNA and protein during the natural estrous cycle to increase our understanding of how this uterine secretory protein is regulated under physiological conditions. There was a positive correlation between LTF mRNA expression in the genital tract and serum estradiol (E2) concentrations. When E2 peaked in proestrus, LTF mRNA and protein were expressed in the uterus; however, during metestrus, when both E2 and progesterone levels were high, LTF mRNA was expressed, while LTF protein was decreasing. LTF protein expression may be hindered by progesterone or some other local factor in the endometrial epithelium after ovulation. Immunohistochemistry demonstrated two distinct staining patterns for LTF in the vaginal and endometrial epithelium. In one staining pattern, the colorimetric reaction was noted over the cytoplasm, and in the other, the nuclear region stained more intensely. This suggests the possibility that in addition to its known role as a secretory protein, LTF may be transported to the nucleus, serving an autocrine role. Our results also indicated that LTF protein is a useful marker for tracking PMN. Nonproliferating epithelial cells in the vagina and endometrium may synthesize chemotactic and/or adhesion molecules for PMN. PMID- 1505478 TI - Sex difference in the effect of mating on c-fos expression in luteinizing hormone releasing hormone neurons of the ferret forebrain. AB - The pulsatile secretion of LH was previously found to rise in female ferrets after receipt of an intromission, whereas in males that achieved an intromission, both LH and testosterone secretion were either reduced or unchanged. We sought to determine whether this sexually dimorphic pattern of LH secretion reflects a sex difference in the effect of mating on the activity of forebrain neurons that secrete LHRH. Immunocytochemical methods were used to localize the nuclear protein product of the immediate early gene, c-fos, as an index of increased neuronal activity after mating. Nuclear FOS immunoreactivity (FOS-IR) was monitored in LHRH-IR neurons as well as other non-LHRH forebrain neurons. In confirmation of previous reports, LHRH-IR perikarya in ferrets of both sexes were located medially along the base of the brain at rostral, medial, and caudal levels of the preoptic-hypothalamic continuum. In each of these regions a significantly higher percentage of LHRH-IR neurons was colabeled with nuclear FOS IR in mated than in unpaired females. By contrast, an equivalent low percentage of LHRH-IR neurons was colabeled with FOS-IR in mated and unpaired male ferrets. Significantly more FOS-IR neurons (not colabeled with LHRH) were detected in the bed nucleus of the stria terminalis, the medial preoptic area, the dorsal-medial hypothalamus, and the medial amygdala (MA) of mated vs. unpaired females. By contrast, mating significantly augmented FOS-IR only in the MA of male ferrets. The results suggest that the sexually dimorphic pattern of LH secretion that occurs in ferrets after mating reflects a selective activation of LHRH neurons in the female forebrain. This sex-specific increase in the responsiveness of LHRH neurons to mating may depend on input from a limbic circuit which includes the medial amygdala, bed nucleus of the stria terminalis, and medial preoptic area. PMID- 1505479 TI - Effect of human recombinant mullerian inhibiting substance on isolated epithelial and mesenchymal cells during mullerian duct regression in the rat. AB - The effect of human recombinant Mullerian Inhibiting Substance (MIS) on the regression of the Mullerian duct (MD) of female rat fetuses was examined in vitro to determine whether MIS acts on MD epithelium and/or mesenchyme at the critical periods of sexual differentiation. Urogenital ridges (URs) of female rat fetuses at 14.5- to 18.5-days of gestation (plug day = 0) were cultured for 3 days with or without recombinant human MIS in CMRL 1066 medium with 10% female fetal calf serum. In URs from 14.5- and 15.5-day-old fetuses, the cranial portion of the MD regressed almost completely during the 3-day culture period in the presence of MIS, whereas the caudal half to third of the MD remained intact but tapered to a fine point cranially. MDs survived in URs from 16.5-day-old fetuses cultured in the presence of MIS except that the cranial portion of the MDs was deformed. MIS did not elicit regression of MDs in URs obtained from 17.5- and 18.5-day-old fetuses, but instead caused the MD epithelium to form bulges projecting into the mesenchyme. MD epithelium at 15.5-days of gestation was separated from the surrounding UR mesenchyme, and both components (MD epithelium and mesenchyme) were cultured separately for 3 days in the presence or absence of MIS. Both epithelial and mesenchymal cells survived in the presence or absence of MIS. MD epithelium formed typical epithelial colonies, whereas UR mesenchyme spread as fibroblastic cells. Analysis of labeling index after incorporation of [3H] thymidine demonstrated that MD epithelial DNA synthesis was not influenced by MIS. In contrast, mesenchymal labeling index was reduced significantly by MIS. This effect of MIS on UR mesenchyme in conjunction with earlier histological observations of mesenchymal condensation during MD regression and an absence of direct effects of MIS on the epithelium suggests that MIS elicits its effect on the MD epithelium via the surrounding mesenchyme. PMID- 1505480 TI - Multiple forms of affinity-labeled estrogen receptors in rat distinct pituitary cells. AB - The presence of multiple monomeric forms has been described for estrogen receptor (ER) in different target tissues. Using [3H]tamoxifen aziridine ([3H]TA) to covalently label ER and sodium dodecyl sulfate-polyacrylamide gel electrophoresis to analyze labeled products, ER forms were investigated in pituitary cytosol and purified nuclei from male rats. ER forms were also compared in cellular extracts from gonadotrope-enriched populations (GP), prepared using the fast method of centrifugal elutriation, and from lactotrope-somatotrope fractions (LSP), obtained by sequential use of both elutriation and Percoll gradient sedimentation. A major labeled protein of 60,000-65,000 mol wt (M(r)) and a minor species of 50,000-55,000 M(r) were found in the pituitary cytosol and nuclear extracts covalently labeled with [3H]TA. The same results were obtained after ER covalent labeling from cellular extracts or intact dispersed cells. In gonadotrope-enriched cell population (greater than or equal to 50% LH immunoreactive cells), the 65,000 M(r) species is the single unique ER form; in the LSP (80% PRL- and GH-immunoreactive cells), the major TA-labeled species is the 50,000 M(r) form, while the 65,000 M(r) ER is hardly detectable. Thus, the prevalence of 65,000 M(r) protein in the initial cell population can be explained by the higher number of binding sites per gonadotrope than per lactotrope cell. In conclusion, ER heterogeneity is demonstrated in pituitary cell populations. The source of this heterogeneity could be due to 1) different ER mRNAs according to cell type, or 2) a specific posttranslational processing, such as proteolytic activity within lactotrope cells. PMID- 1505481 TI - Expression of 4-ene steroid 5 alpha-reductase messenger ribonucleic acid in the rat epididymis during postnatal development. AB - The regulation of epididymal 5 alpha-reductase mRNA is multifactorial and segment specific. To further investigate the regulation of the message for the enzyme, the expression of 5 alpha-reductase mRNA in the rat epididymis was studied as a function of postnatal development. Developmental changes in 5 alpha-reductase mRNA concentrations were assessed by probing Northern blots with the full-length cDNA for rat steroid 5 alpha-reductase. In the first experiment the effect of postnatal age on 5 alpha-reductase mRNA concentrations in the caput-corpus and cauda epididymides was studied. Male rats, taken at 1-week intervals between the ages of 7-91 days, were used. In both epididymal regions, the mRNA for 5 alpha reductase was present at all ages examined; it appeared in the immature animal at least 2 weeks before detectable 5 alpha-reductase enzyme activity. In the caput corpus epididymidis, mRNA levels for 5 alpha-reductase decreased by half between postnatal days 7 and 21, rose 5-fold by day 56, and then remained constant through day 91. No change with postnatal age, however, was observed in the cauda epididymidis. In the second experiment, the longitudinal distribution of 5 alpha reductase mRNA on postnatal days 21, 42, 49, 56, 77, and 91 was studied. The mRNA levels for 5 alpha-reductase increased remarkably, by 6- to 7-fold, in the initial segment of the caput epididymidis between postnatal days 21 and 42 and stayed constant thereafter. However, no significant change comparable to that found in the initial segment was observed in the adjacent proximal caput region or in any of the other epididymal segments. Thus, the 5-fold rise in 5 alpha reductase mRNA concentrations that occurred in the caput-corpus epididymidis in the first experiment can be attributed solely to changes in the initial segment. We conclude that steady state concentrations of epididymal 5 alpha-reductase mRNA vary dramatically at different postnatal ages and are highly specific with respect to epididymal segment. PMID- 1505482 TI - In vivo evidence that inhibin is a gonadotropin surge-inhibiting/attenuating factor. AB - Hyperstimulation of ovarian function through exogenous gonadotropin administration suppresses the preovulatory surges of both LH and FSH. This phenomenon has been demonstrated to be the result of a non-steroidal factor released from the ovary that has been designated as either gonadotropin surge inhibiting factor or attenuating factor (GnSIF/AF). To examine the possibility that inhibin might possess the activity ascribed to this factor, endogenous inhibin was immunoneutralized in female rats under conditions known to stimulate GnSIF/AF activity. Inhibin-like immunoreactivity was found to be significantly elevated in FSH-treated rats prior to the time of the gonadotropin surges. Spontaneous preovulatory surges of both LH and FSH were observed in saline treated (control) rats that were subsequently treated with either anti-inhibin serum (AS) or normal sheep serum (NS). FSH-treatment completely prevented the occurrence of gonadotropin surges in rats subsequently treated with NS. In FSH injected rats subsequently treated with AS, however, normal preovulatory surges of both LH and FSH were observed. These results indicate that inhibin may be the factor responsible for the suppression of the preovulatory gonadotropin surges in FSH-treated rats and, at least in this species, may be a GnSIF/AF. PMID- 1505483 TI - Modulation of cytoplasmic calcium signaling in rat pituitary gonadotrophs by estradiol and progesterone. AB - The stimulatory action of GnRH on gonadotropin secretion from cultured rat pituitary cells is modulated by estradiol (E) and progesterone (P). Since secretory responses to GnRH are initiated by phosphoinositide hydrolysis and Ca2+ mobilization, the effects of gonadal steroids on the pattern of Ca2+ signaling were analyzed in single pituitary gonadotrophs. Increasing concentrations of GnRH elicited a spectrum of [Ca2+]i signals in single gonadotrophs, ranging from subthreshold to threshold-oscillatory and biphasic (spike & plateau) responses. In E-treated gonadotrophs, short-term P treatment shifted subthreshold [Ca2+]i responses to oscillatory and oscillatory to biphasic responses, whereas long-term P treatment shifted oscillatory to subthreshold [Ca2+]i response profiles. These changes parallel the effects of P on GnRH-induced LH release, and indicate that the modulatory effects of ovarian steroids on gonadotropin secretion include a significant action on the Ca2+ signaling pathway. PMID- 1505484 TI - Structure of human type II 5 alpha-reductase gene. AB - The best known activity of steroid 5 alpha-reductase is the transformation of testosterone into dihydrotestosterone, the most potent androgen. Two types of human steroid 5 alpha-reductase cDNAs and the type I gene have previously been isolated and characterized. This report describes the isolation and characterization of the human type II 5 alpha-reductase gene, the gene most likely responsible for male pseudohermaphroditism due to 5 alpha-reductase deficiency as well as the one presumed to be involved in a major androgen-related diseases such as prostate cancer and benign prostatic hyperplasia. The type II 5 alpha-reductase gene contains five exons of 352, 164, 102, 151 and 1695 bp, respectively, which share 43.8% to 64.1% homology with exons of the corresponding type I gene. These exons are separated by four introns of greater than 29, and approximately 2.3, 2.0 and 3.0 kb. Analysis of primer extension products by polyacrylamide gel electrophoresis as well as by subcloning and sequencing reveals a start site located 71 nucleotides upstream the ATG initiating codon. PMID- 1505485 TI - The effect of hypothyroidism on Sertoli cell proliferation and differentiation and hormone levels during testicular development in the rat. AB - In this study we show that 6-propyl-2-thiouracil (PTU) treatment of Wistar rats from birth up to day 26 p.p. retards the morphological differentiation of Sertoli cells, and prolongs the proliferation of these cells up to day 30. Sertoli cell numbers per testis, determined at day 36, were increased by 84% compared to controls. PTU treatment increased serum thyroid-stimulating hormone (TSH) levels and reduced serum levels of thyroxine (T4) from 5 days onwards, indicative of severe hypothyroidism. Follicle-stimulating hormone (FSH) levels were reduced from day 5 to 9, normal at day 12 and 16, and reduced again from day 20 to 36. Inhibin levels were decreased from day 9 to 20 and increased at 36 days of age. The increase in the number of Sertoli cells per testis in PTU treated rats, as has been reported in the present study, is likely to be responsible for the increased testis size observed by other groups (1) in these animals, when adult. PMID- 1505486 TI - Biliary stent occlusion--a problem solved with self-expanding metal stents? European Wallstent Study Group. AB - The main limitation in the endoscopic palliation of malignant biliary obstruction is due to stent blockage. One of the factors thought to be of importance is the diameter of the endoprosthesis. In this paper, we report the results of a multicenter European study with a one cm diameter self-expanding metal stent (Wallstent) in 103 patients with malignant biliary obstruction. Insertion of the stent following guidewire positioning was successful in 97.1% of the patients without any cases of de novo cholangitis developing after the endoscopic procedure. The median follow-up for the entire group was 145 days. In all but 3 patients, the stent expanded to more than 80% of its maximum diameter. Two patients had ongoing cholangitis after stent insertion. Long-term complications manifested by late cholangitis, were seen in 18% of the cases after a median interval of 125 days. The occlusion rate by biliary sludge was 5% after a median time period of 175 days which is substantially less than the 21% occlusion rate reported for polyethylene stents. In conclusion, our results show that the Wallstent can be easily placed in distal and mid-CBD strictures after guidewire passage, with most of the patients having a- good drainage effect. The occlusion rate by biliary sludge is significantly less than for conventional polyethylene stents, but the occlusion by tumor ingrowth is substantial. A disadvantage is the high cost of the Wallstent. Further randomized trials will be required to determine the cost-benefit ratio for the use of this stent. PMID- 1505487 TI - Technical failure of biliary metal stent deployment in a series of 116 applications. AB - Biliary metal stents are thought to offer improved long-term palliation of malignant biliary obstruction due to a lower incidence of migration and clogging. Placement of these stents is technically more complicated than that of plastic endoprostheses and requires two experienced physicians. We report the incidence and reasons for apparent malfunction of expandable metal stent deployment (Wallstents and Strecker stents). In 116 applications of 82 Wallstents (endoscopic approach: n = 33, transhepatic approach: n = 49), we observed 19 cases of stent malfunction due to technical problems of stent delivery. In 13 cases (15.8%), the restraining membrane of the Wallstent could not be retracted sufficiently to deliver the stent. There were 6 (17.6%) failures in 34 cases of Strecker stent deployment. In 3 cases, we noted difficult balloon removal, including avulsion of the balloon catheter shaft within the endoscope during attempted balloon removal in one case. In one case, the Strecker stent could only be released partially, requiring subsequent endoscopic extraction. In two patients, only partial expansion of one end of the Strecker stent could be achieved. Given the significant malfunction rate of expandable metal stents during stent delivery, further improvements in the delivery system of the metal stents are required. PMID- 1505488 TI - Three years experience with endoscopic variceal ligation for treatment of bleeding varices. AB - Endoscopic variceal ligation (EVL) was developed as an alternative to endoscopic variceal sclerosis (ES) because of the high complication rate seen with ES. The new technique involves placement of small elastic bands around the variceal channels in the distal esophagus. The first 146 consecutive patients treated with EVL during the period from August, 1986 to July, 1989 are reported. Portal hypertension was caused by alcoholic liver disease in 93 of these patients. The average age of the patients was 53 years and 66% were males. All of the patients had recently bled from esophageal varices. At the time of treatment, 23% of the patients were actively bleeding. They were all treated acutely with EVL and had repeated treatments with the long-term goal of variceal eradication. The overall survival was 73%. Varices were eradicated or reduced to grade one in 78% of the 125 patients who were followed for more than 30 days. Variceal eradication required a mean of 5.5 sessions. Recurrent bleeding occurred in 44% of the total patient population. There were no major complications from EVL. It is concluded from this non-randomized experience that EVL is an effective treatment for bleeding esophageal varices and that it appears to be as effective as sclerotherapy with fewer complications. PMID- 1505489 TI - Silicone-covered expandable metallic stents in the esophagus: an experimental study. AB - Modified silicone-covered Gianturco expandable metallic stents were placed in the normal esophagus of six young pigs. Following endoscopic examination, the stents were placed using endoscopic and fluoroscopic control. The animals were observed for eating behavior and weight gain. Stents appeared to be tolerated well based on these parameters. Three stents remained in position for the full study period, and three stents migrated into the stomach during the study. The pigs were sacrificed at four weeks and postmortem examination performed. Esophageal wall thickening and nodular inflammation were noted at the sites where the wire skirts penetrated the mucosa. Injury was limited to the region of the wire skirts and there was no injury due to the radial force of the stent body. There was no free perforation. This preliminary study suggests that endoscopic and fluoroscopic placement of modified silicone-covered Gianturco stents in the esophagus is feasible and safe. More extensive animal studies, followed by clinical investigation for palliation of malignant strictures, are warranted. PMID- 1505490 TI - Metallic mesh stents--is the expanse worth the expense? PMID- 1505491 TI - Helicobacter pylori infection--a common worldwide environmental risk factor for gastric cancer? PMID- 1505492 TI - Early recurrence of obstructive jaundice after placement of a self-expanding metal endoprosthesis. AB - Self-expanding metal endoprostheses have ben used in the treatment of malignant obstructive jaundice for a few years. We report on a patient with obstructive jaundice due to a metastasis of a squamous cell lung cancer into the pancreatic head who received an expandable metal endoprosthesis and suffered recurrent jaundice and cholangitis after 38 days. On repeat ERCP, a very narrow stenosis was seen in the stent lumen caused by tumor ingrowth through the mesh. Intraluminal biopsies showed squamous cell carcinoma. A 10 Fr plastic endoprosthesis was inserted through the self-expanding stent with good drainage. On the basis of this experience, we feel that when faced with a patient with obstructive jaundice due to metastatic disease from a rapidly progressive carcinoma, the use of the currently available self-expanding metal endoprosthesis should be discouraged until the results of prospective studies with large numbers of patients have proven its superiority over the plastic endoprostheses. Meanwhile, modifications to prevent tumor ingrowth through the mesh of the stent are under investigation. PMID- 1505493 TI - Haemorrhage due to erosion of a metal biliary stent through the duodenal wall. AB - Self-expanding, metal biliary stents have recently been used in malignant obstructive jaundice as their large diameter reduces the likelihood of occlusion by biliary sludge and bacterial biofilm. However, there is a significant rate of late obstruction by tumour overgrowth and infiltration through the wire mesh. Our case of stent erosion through the duodenal wall, resulting in massive haemorrhage, is a hitherto unreported serious complication of the Wallstent (Schneider). Its occurrence may be suggested by continuous upper abdominal pain, gastrointestinal bleeding or late expansion of the stent. PMID- 1505494 TI - Endoscopic application of Gianturco-Rosch biliary Z-stent. AB - Ginaturco-Rosch Z-stent is a new self-expanding stainless steel stent for drainage of the obstructed biliary system. It has been used only with a percutaneous transhepatic technique. We describe a new method for endoscopic retrograde placement of a Gianturco-Rosch biliary Z-stent. This report describes our experience for endoscopic application of a Gianturco-Rosch biliary Z-stent in a patient with a benign stricture and multiple common bile duct stones. PMID- 1505495 TI - Acute pancreatitis complicating the insertion of a self-expandable biliary metal stent. AB - A patient is reported who developed acute pancreatitis complicated by pseudocyst formation immediately after the insertion of a self-expanding metallic biliary stent via the percutaneous route. The distal end of the stent was positioned into the duodenum. Endoscopists should be aware of this potential complication of metallic biliary stents. PMID- 1505496 TI - The analysis of human serum transferrins with the PhastSystem: quantitation of microheterogeneity. AB - The PhastSystem was used for three different analyses of human serum transferrins (Tf) by isoelectric focusing: (i) The distribution of iron over the two iron binding sites by separation of the four forms: apoTf, TfFeC, FeNTf and Fe2Tf by using less than 1 microL serum or plasma. The focused bands were visualized by immunoprecipitation and quantified by densitometry. (ii) The relative proportions of the diferic sialo-transferrin fractions in human sera or plasma were determined in a similar way. (iii) The presumed genetic variants can be determined. The methods are easy and reproducible and require much less sample (0.3 microL), time (1 h per run) and antibody (10 microL/sample) than crossed immunoelectrofocusing. PMID- 1505497 TI - Analysis of carbohydrate-mediated heterogeneity and characterization of N-linked oligosaccharides of glycoproteins by high performance capillary electrophoresis. AB - Capillary zone electrophoresis (CZE) has been investigated as an alternative method to analyze the carbohydrate moieties of glycoproteins. Carbohydrate mediated microheterogeneity of the recombinant plasminogen activator (rt-PA) was examined. The glycoprotein was resolved in multiple electrophoretic species using CZE but the separation was complicated by adsorption of the molecules to the wall of the capillary. The influence of several parameters, such as pH, molarity of the buffer and addition of a cationic additive, on the separation of glycopeptides was investigated. High resolution and reproducible separations of rt-PA glycopeptides carrying hybrid and complex type chains were obtained using either a 100 mM phosphate buffer, pH 6.6, or a 100 mM Tricine buffer, pH 8.2, containing 1.25 mM of putrescine. N-Oligosaccharides from fetuin, t-PA and alpha 1-acid glycoprotein were separated within 20 min on the basis of both their sialic acid content and their structure. The use of an oligosaccharide fingerprinting technique, such as the present one, could have many applications in biotechnology to assess, for example, the consistency of production of a glycoprotein or for analytical glycoprotein chemistry. PMID- 1505498 TI - Improvement of BF typing and of BF F subtyping after neuraminidase treatment in the unconverted and converted factor B. AB - When neuraminidase-treated sera are analyzed by agarose gel isoelectric focusing, the factor B (BF) banding pattern is reduced to predominantly one major band without cathodically positioned bands. This not only makes unequivocal typing of BF allotypes possible but also the reliable distinction of all BF F subtype phenotypes with delimitation of "BF F subtype variants". With this new method, serum aging affects the BF determination to a lesser extent than when applying methods that separate native sera. We show that sialylation is not responsible for the BF F subtype polymorphism. All of the investigated BF allotype bands, including those characteristic of the subtypes, show functional hemolytic activity. The banding pattern after removal of neuraminic acid residues ranges from pH 6.8 to 7.3 for factor B, from pH 5.3 to 5.9 for the Ba fragment, and from pH 8.2 to 8.7 for the Bb fragment. The protein structure of factor B is also discussed. Eliminating the superimposition of bands in different BF allotypes, as demonstrated by these methods, proved to be necessary for the detection of hypomorphic BF gene products (BF QL), which are expressed by assumed BF*Q0 alleles in heterozygous genotypes. This allows investigation of BF*Q0 alleles on a protein level, which complements molecular genetic approaches. PMID- 1505499 TI - Analysis of collagen type III by uninterrupted sodium dodecyl sulfate polyacrylamide gel electrophoresis and immunoblotting: changes in collagen type III polymorphism in aging rats. AB - A new method of type III collagen analysis by uninterrupted sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) combined with immunoblotting was developed. The electrophoresis was carried out with gels containing 4 M urea. A negatively charged reducing agent, thioglycolic acid, was added to the running buffer of the cathodic reservoir between 15 and 20 min after Bromphenol Blue (BPB) migrated to the top of the separating gel, to reduce interchain disulfide binding of the collagen. The polymorphic type III collagens, i.e., an alpha-chain derived from a trimer [alpha 1(III)]3 with interchain disulfide bonds but without covalent cross-links, alpha 1(III), a beta-chain with covalent cross-links, beta(III), or an alpha-chain released from a trimer without reduction of the disulfide bonds, alpha*1(III), were identified by immunostaining and quantified by densitometry. Using this method, changes in collagen type III polymorphism with aging were examined in the aorta, brachial artery, and skin of rats. The total quantity of collagen type III decreased with aging in all tissues. beta(III) was the major component in the aorta and brachial artery, but alpha 1(III) was the major component in the skin. With increasing age from 3 to 60 weeks, the ratio of beta(III) to alpha 1(III), which is correlated with the extent of covalent cross-linking, showed a steep increase in the aorta but only a slight increase in the skin and it remained almost constant in the brachial artery.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1505500 TI - A new concept for sequencing DNA by capillary electrophoresis. AB - It is proposed that the scaling symmetry of constant charge density with increasing molecular weight, which prevents the separation by electrophoresis of DNA molecules in solution (with respect to molecular weight) be broken by the attachment of a perturbing entity (protein, virus or charged sphere) to one end of the molecule. An application of this idea to a concept for sequencing DNA by capillary electrophoresis is discussed, and the possibility of using the reattachment of the RecA protein to separate large segments of DNA in solution by electrophoresis following sequence-specific cleavage is mentioned. PMID- 1505501 TI - A new technique for detecting oxytocinase activity in electrophoresis gels. AB - A sensitive staining method for the detection of oxytocinase (EC 3.4.11.3) activity in electrophoresis gels has been described. The method is based on the enzymatic release of p-nitroaniline (PNA) from two specific synthetic oxytocinase substrates, S-benzyl-L-cysteine-p-nitroanilide (BCN) and L-leucine-p-nitroanilide (LN), respectively. The PNA is then diazotized with sodium nitrite and subsequently coupled to a chromogen, N-(1-naphthyl)-ethylenediamine dihydrochloride (NED) to produce a deep pink/magenta colored azo-dye at the site of oxytocinase activity. PMID- 1505502 TI - Tissue-specific pattern of nonhistone high mobility group proteins in various organs of the chicken. AB - Electrophoretic analysis of tissue-specific differences of nonhistone high mobility group (HMG) proteins from nuclei of various organs of the chicken revealed that in organs with a higher proportion of replicating cells (thymus, Bursa Fabricii, spleen) the relative amount of HMG-17 is considerably higher than that of HMG-14; however, in transcriptionally active organs with a very small proportion of replicating cells (glandular stomach, liver) HMG-14 and HMG-17 are present at roughly equal and low amounts. In glandular stomach, liver and spleen, the relative contents of both HMG-1 and HMG-2 are markedly lower than in thymus and Bursa Fabricii. Moreover, the total amount of HMG proteins is higher in those organs which contain replicating lymphocytes. PMID- 1505503 TI - Separation of proteins by sodium dodecyl sulfate-polyacrylamide gel electrophoresis in the presence of soluble, aqueous polymers: Ficoll and polyvinylpyrrolidone. AB - In previous studies we have demonstrated that water soluble polymers of dextran and methylcellulose, when incorporated into sodium dodecyl sulfate (SDS) polyacrylamide gels, can be used to sharpen the protein bands. We have extended these studies to enhance the separations in the mid-molecular weight range. Enhanced separation of protein molecular weight markers between 30,000-67,000 was best achieved in SDS-gels containing 2.5% polyvinylpyrrolidone (average molecular weight 10,000). PMID- 1505504 TI - Anthropometric, muscle strength, and spinal mobility characteristics as predictors in the rating of acceptable loads in parcel sorting. AB - The rating of acceptable load (RAL) attained with a standard test (RALSt) and a wrk-simulating test (RALW) for postal parcel sorting was related to anthropometric, muscle strength, and spinal mobility characteristics of 18 male sorters. The subjects comprised a subsample of 103 experienced male sorters who carried out the RAL tests at postal sorting centres. The dynamic hand-grip endurance correlated significantly (p = 0.036) to the RALSt results. Correspondingly, there was a significant correlation (p = 0.044) between the ratio of maximal isometric strength of trunk extension to body weight and the RALW. The dynamic hand-grip endurance predicted 26% of the variation in the RALSt; in the RALW the maximal isometric strength of trunk flexion to body weight ratio predicted 24%. The subjects who rated heavier weights for RALSt tended to have a better trunk mobility. The dynamic endurance of hand-grip muscles, trunk strength, and spinal flexibility seemed to be the most powerful predictors for the psychophysically assessed 'acceptable loads' in experienced workers performing manual materials handling tasks. PMID- 1505505 TI - Logistical and ergonomic transportation capacity for refuse collection workers: a work physiology field study. AB - In a work physiology field study, the work flow and the electrocardiogram were recorded throughout whole shifts for six male refuse (garbage) collection workers who transported and emptied 1.1 m3 refuse containers. The work rate (WR), indicated by the number of 1.1 m3 containers emptied per unit of time, and the work pulse rate (WPR) were determined in the data evaluation. The work pulse rate increases with the work rate. The functional relationship can be approximated by a linear regression function (WPR = 20.9 + 35.8.WR). The work pulse rate reaches such high values that it must be assumed that the work cannot be performed continuously throughout the whole working day. Consequently, regular breaks should be provided. When determining the necessary duration of the breaks, it was assumed that an equilibrium between fatigue and recovery should be maintained during the working day. The recovery breaks should be at least long enough for the heart rate to return to the resting level. The necessary duration of the breaks was determined on the basis of the present field study and the laboratory investigations described in the literature. A minimum duration of 10 min per working hour results from the calculations. The breaks should be taken regularly at about hourly intervals. A transportation-capacity model is provided for the planning of the deployment of refuse workers. It permits calculation of the number of 1.1 m3 containers a three-man crew, comprising the refuse collection truck driver and two loaders, can empty during one shift. Both the logistical and ergonomic transportation capacities can be determined using the model. The logistical transportation capacity (TCL) indicates the number of containers which can be emptied per shift by a crew when only criteria such as the optimal utilization of the working time are considered. The ergonomic transportation capacity (TCE) is understood as the number of containers which can be emptied per shift taking into consideration the workers' strain and the recovery breaks they require. TCE amounts to between about 140 and 160 containers per shift depending on the type of city district. TCL is higher by between 20 and 30 containers per shift. In order to meet the demand of protecting workers' health, the number of containers to be emptied per shift by a three-man crew should not exceed the ergonomic transportation capacity. PMID- 1505506 TI - The metabolic cost of backpack and shoulder load carriage. AB - Eleven healthy male volunteer soldiers (mean [SD] age 24.0 [2.8] years, stature 174.1 [5.2] cm, body weight 73.2 [10.8] kg, body fat 14.2 [5.0]% and maximal oxygen uptake 4.1 [0.4] 1 min-1) walked at 4.8 km h-1 on a motor driven treadmill for 5 min at each of three gradients (0, 2.5 and 5%) whilst carrying a two-part 26 kg load either on each shoulder or strapped to a backpack frame. The load was made up of two cylinders, one weighing 18.4 kg and the other weighing 7.6 kg. For all treadmill gradients the mean (SD) backpacking heart rates and oxygen uptakes (0% gradient, 122 [10] beats min-1, 1.51 [0.11] 1 min-1; 2.5% gradient, 135 [10] beats min-1, 1.81 [0.13] 1 min-1; 5% gradient, 155 [7] beats min-1, 2.21 [0.11] 1 min-1) were significantly (p less than 0.001) lower than for shoulder load carriage (0% gradient, 130 [9] beats min-1, 1.70 [0.12] 1 min-1, 2.5% gradient, 147 [8] beats min-1; 2.01 [0.10] 1 min-1; 5% gradient 164 [9] beats min-1, 2.39 [0.11] 1 min-1). The relative oxygen cost of backpacking was 4.3-4.7% VO2 max lower than for shoulder load carriage. It is concluded that the metabolic cost of backpacking an asymmetric two part 26 kg load was significantly less than for shoulder load carriage when walking at 4.8 km h-1 on a treadmill over gradients of 0-5%.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1505507 TI - Evaluation of impact loading in overhead work using a bolt pistol support. AB - This paper evaluates the effects of a bolt gun support stand on impact loading of the hand-arm system while firing spiked bolts into a steel beam. Ten healthy male subjects fired two bolts into the centre of the beam, one with and one without the aid of the support stand. During firing of a bolt gun, the shock sequences were recorded by two accelerometers. The analysis showed that peak values of acceleration decreased more than eightfold during firing with the bolt pistol support. The shock damping effect due to the bolt support was noted at the thumb (metacarpal level) and elbow bones. PMID- 1505508 TI - Physical training: a tool for increasing work tolerance limits of employees engaged in manual handling tasks. AB - The lack of physical fitness is a contributing factor to the etiology of musculoskeletal disorders resulting from the manual handling of material in industry. Thus the major objectives of this paper were (1) to discuss the role of physical fitness in the control of occupational injuries; (2) to review techniques available in the exercise physiology literature for increasing human physical capacity in industry; and (3) to review and evaluate studies on the effects of physical training on individuals engaged in manual handling tasks. PMID- 1505509 TI - Effects of job-simulated flexibility and strength-flexibility training protocols on maintenance employees engaged in manual handling operations. AB - This study examined the effects of four flexibility and strength-flexibility training protocols on the dynamic strength, endurance time, and truncal flexibility of 24 maintenance employees engaged in manual material handling operations. The study was conducted over an 8-week period. Significant improvement in physical capacity was obtained through flexibility training either by a progressive increase in the holding time with fixed exercise repetition or a progressive increase repetition with fixed holding time. The flexibility and strength-flexibility training protocols exhibited similar effects on physical capacity. It was suggested that a follow-up flexibility protocol should be performed on a daily basis in order to maintain the gains obtained in flexibility during the intensive/short training programme. PMID- 1505510 TI - Special issue in honour of Professor M. M. Ayoub. PMID- 1505511 TI - Understanding and evaluating manual handling injuries: NIOSH research studies. AB - This paper presents an overview of NIOSH research aimed at characterizing and identifying intervention strategies for reducing musculoskeletal injuries during manual handling activities. Surveillance and evaluative research projects are reviewed. Future research directions of the Institute are also discussed. PMID- 1505512 TI - Ergonomic workplace assessment in a health care context. AB - Nurses, together with other groups in the caring professions, show a high incidence of musculoskeletal injuries as a consequence of the handling of equipment and patients. This is an internationally recognized consequence of the work in these professions, and studies worldwide have investigated these problems. The UK Health and Safety Executive, as well as the European Community (EC) Directives, require workplaces to be assessed for their hazardousness. Ergonomics is the recognized discipline in relation to assessing whether the work, equipment, or environment match the capacities of the people concerned. An assessment procedure is presented, together with proposals for its use, which can form the basis for the ergonomic assessment of workplaces in health care, and give guidance for their improvement. PMID- 1505513 TI - A novel and conserved salt-induced protein is an important determinant of salt tolerance in yeast. AB - We have isolated a novel yeast gene, HAL1, which upon overexpression improves growth under salt stress. In addition, disruption of this gene decreases salt tolerance. Therefore HAL1 constitutes a rate-limiting determinant for halotolerance. It encodes a polar protein of 32 kDa located in the yeast cytoplasm and unrelated to sequences in data banks. The expression of this gene is increased by high concentrations of either NaCl, KCl or sorbitol. On the other hand, the growth advantage obtained by overexpression of HAL1 is specific for NaCl stress. In cells overexpressing HAL1, sodium toxicity seems to be counteracted by an increased accumulation of potassium. The HAL1 protein could interact with the transport systems which determine intracellular K+ homeostasis. The HAL1 gene and encoded protein are conserved in plants, being induced in these organisms by salt stress and abscisic acid. These results suggest that yeast serves as a convenient model system for the molecular biology of plant salt tolerance. PMID- 1505514 TI - Three-dimensional crystal structure of recombinant murine interferon-beta. AB - The crystal structure of recombinant murine interferon-beta (IFN-beta) has been solved by the multiple isomorphous replacement method and refined to an R-factor of 20.5% against 2.6 A X-ray diffraction data. The structure shows a variant of the alpha-helix bundle with a new chain-folding topology, which seems to represent a basic structural framework of all the IFN-alpha and IFN-beta molecules belonging to the type I family. Functionally important segments of the polypeptide chain, as implied through numerous gene manipulation studies carried out so far, are spatially clustered indicating the binding site(s) to the receptor(s). Comparison of the present structure with those of other alpha helical cytokine proteins, including porcine growth hormone, interleukin 2 and interferon gamma, indicated either a topological similarity in chain folding or a similar spatial arrangement of the alpha-helices. PMID- 1505515 TI - Sequences directing dihydrolipoamide dehydrogenase (E3) binding are located on the 2-oxoglutarate dehydrogenase (E1) component of the mammalian 2-oxoglutarate dehydrogenase multienzyme complex. AB - Sequences located in the N-terminal region of the high M(r) 2-oxoglutarate dehydrogenase (E1) enzyme of the mammalian 2-oxoglutarate dehydrogenase multienzyme complex (OGDC) exhibit significant similarity with corresponding sequences from the lipoyl domains of the dihydrolipoamide acetyltransferase (E2) and protein X components of eukaryotic pyruvate dehydrogenase complexes (PDCs). Two additional features of this region of E1 resemble lipoyl domains: (i) it is readily released by trypsin, generating a small N-terminal peptide with an apparent M(r) value of 10,000 and a large stable 100,000 M(r) fragment (E1') and (ii) it is highly immunogenic, inducing the bulk of the antibody response to intact E1. This 'lipoyl-like' domain lacks a functional lipoamide group. Selective but extensive degradation of E1 with proteinase Arg C or specific conversion of E1 to E1' with trypsin both cause loss of overall OGDC function although the E1' fragment retains full catalytic activity. Removal of this small N-terminal peptide promotes the dissociation of dihydrolipoamide dehydrogenase (E3) from the E2 core assembly and also affects the stability of E1 interaction. Thus, structural roles which are mediated by a specific gene product, protein X in PDC and possibly also the E2 subunit, are performed by similar structural elements located on the E1 enzyme of the OGDC. PMID- 1505516 TI - Transmembrane helical interactions: zeta chain dimerization and functional association with the T cell antigen receptor. AB - Members of the zeta family of receptor subunits (zeta, eta and gamma) are structurally related proteins found as components of the T cell antigen receptor (TCR) and certain Fc receptors. These proteins share the ability to form disulfide-linked dimers with themselves and with other members of the family. Comparison of the amino acid sequences of zeta and gamma reveals a significant degree of homology, which is highest within their membrane-spanning domains. Analysis of their transmembrane sequences on a helical wheel projection suggests that all of the identical amino acids are clustered on one face of a potential alpha-helix. This face contains the only cysteine residue within zeta, suggesting that this conserved region may function to mediate dimerization. Indeed, replacing the transmembrane domain of the Tac antigen (alpha chain of the interleukin-2 receptor) by that of the zeta chain resulted in the formation of disulfide-linked dimers of Tac. The conserved aspartic acid residue found in the zeta and gamma transmembrane sequences was found to play a role in disulfide linkage. Replacing the aspartic acid with a lysine but not with an alanine or valine residue allowed formation of disulfide-linked dimers. The ability of the aspartic acid residue to support dimerization was dependent upon its position within the helix. Thus, these observations indicate that residues within the zeta transmembrane domain play a critical role in the formation of disulfide-linked dimers. Expression of zeta mutants in zeta-deficient T cells revealed that the zeta transmembrane domain is also responsible for reconstituting transport of functional TCR complexes to the cell surface and differentiated the requirements for disulfide-linked dimerization per se from assembly of the TCR complex. PMID- 1505517 TI - The human poly(ADP-ribose) polymerase nuclear localization signal is a bipartite element functionally separate from DNA binding and catalytic activity. AB - Poly(ADP-ribose) polymerase (PARP, EC 2.4.2.30) is a zinc finger DNA-binding protein involved in DNA repair processes in eukaryotes. By deletion and extensive site-directed mutagenesis, its DNA-binding domain fused to the N-terminus of beta galactosidase was shown to contain a nuclear localization signal (NLS) of the form KRK-X(11)-KKKSKK (residues 207-226). In vitro, both the DNA-binding capacity and the polymerizing activity of PARP are independent of the nuclear location function. Each basic cluster is essential but not sufficient on its own for this function, while both motifs together are. Crucial basic amino acids (K207, R208 and K222) in each of these two motifs are required for nuclear homing. The results presented here support the concept that the human PARP NLS is an autonomous functional element and belongs to the class of bipartite NLSs. We show that the linear distance between the two basic clusters is not crucial. Insertional mutation analysis leading to a partial reversion of the cytoplasmic phenotype displayed by the mutant K222I highlights the crucial positioning of this lysine. The structure-function relationship of the second cluster of basic residues is discussed. PMID- 1505518 TI - A novel gene, spp91-1, suppresses the splicing defect and the pre-mRNA nuclear export in the prp9-1 mutant. AB - Processing and export of nuclear pre-mRNA are believed to be competing processes in the nucleus. In order to identify factors which are involved in these processes, we isolated suppressors that relieve the growth defect of a prp9-1 temperature-sensitive mutant strain of Saccharomyces cerevisiae. The prp9-1 mutation was previously shown to abolish splicing and to target pre-mRNA to the cytoplasm. One of the suppressors, spp91-1, corrects the prp9-1 growth defect through partial restoration of splicing and by a complete reversion of the pre mRNA escape phenotype. This suppressor is specific for two prp9 alleles and cannot substitute for PRP9 function. The mutant and wild-type alleles of SPP91 were cloned and sequenced. SPP91 encodes a novel protein essential for mitotic growth whose sequence contains motifs indicative of a nuclear localization. In vivo depletion of SPP91 in a prp9-1 genetic background is lethal and is associated with reduced amounts of spliced mRNA and accumulation of pre-mRNA. This observation strongly supports the hypothesis that SPP91 encodes a PRP factor. We suggest that spp91-1 increases pre-mRNA retention in the nucleus by improving the formation of the spliceosome and thereby allowing a larger proportion of the pre-mRNA molecules to be spliced. PMID- 1505519 TI - Histone H3 N-terminal mutations allow hyperactivation of the yeast GAL1 gene in vivo. AB - Recent work has shown that the yeast histone H4 N-terminus, while not essential for viability, is required for repression of the silent mating loci and activation of GAL1 and PHO5 promoters. Because histone H3 shares many structural features with histone H4 and is intimately associated with H4 in the assembled nucleosome, we asked whether H3 has similar functions. While the basic N-terminal domain of H3 is found to be non-essential (deletion of residues 4-40 of this 135 amino acid protein allows viability), its removal has only a minor effect on mating. Surprisingly, both deletions (of residues 4-15) and acetylation site substitutions (at residues 9, 14 and 18) within the N-terminus of H3 allow hyperactivation of the GAL1 promoter as well as a number of other GAL4-regulated genes including GAL2, GAL7 and GAL10. To a limited extent glucose repression is also alleviated by H3 N-terminal deletions. Expression of another inducible promoter, PHO5, is shown to be relatively unaffected. We conclude that the H3 and H4 N-termini have different functions in both the repression of the silent mating loci and in the regulation of GAL1. PMID- 1505520 TI - Hold back of RNA polymerase II at the transcription start site mediates down regulation of c-myc in vivo. AB - Premature termination of transcription is assumed to be an important mechanism of c-myc regulation. Induction of terminal differentiation in the promyelocytic leukemia cell line HL60 by dimethyl-sulfoxide (DMSO) is accompanied by a block of RNA elongation within the first exon of the c-myc gene. We have studied the 3' structure of incompletely elongated transcripts in (i) nuclear RNA of induced and uninduced HL60 cells, (ii) nuclear run-on RNA, and (iii) RNA of in vitro transcribed c-myc constructs. Elongation of c-myc RNA stopped in all three transcriptional systems at similar sites distributed 150-350 bases downstream of the P2 promoter. When HL60 cells were induced to terminal differentiation the short c-myc exon 1 specific RNAs disappeared in nuclear RNA. This implied that RNA polymerase II (pol II) does not continue to transcribe c-myc exon 1 in induced HL60 cells as suggested by earlier nuclear run-on experiments. Therefore, kinetic experiments with small oligonucleotides as probes were performed to determine the start position of pol II on c-myc exon 1 in nuclear run-ons. The results demonstrate that all RNA polymerases are localized at the c-myc P2 promoter in DMSO-treated HL60 cells. Preparation of nuclei for run-on experiments induces a release of pol II from the c-myc P2 promoter leading to the strong nuclear run-on signal on c-myc exon 1. Thus, down-regulation of c-myc in differentiating HL60 cells occurs by retention of pol II at the transcription start site. PMID- 1505521 TI - Homeotic control in Drosophila; the scabrous gene is an in vivo target of Ultrabithorax proteins. AB - The regulatory functions of transcription factors encoded by the Ultrabithorax (Ubx) gene initiate genetic programmes essential for segmental identity and morphogenesis in Drosophila. Based on the formation of DNA-protein adducts in intact nuclei and immunoselection procedure, we cloned genomic targets for Ubx proteins. One clone was studied in detail. It encompasses parts of the last intron and exon of the scabrous (sca) gene, which encodes a secreted protein involved in cellular communication during neurogenesis. Five motifs, presenting the ATTA core, which is shared by most homeodomain binding sites, were found in the nucleotide sequence of this clone. We detail here the dynamic pattern of sca transcript accumulation during embryogenesis and show that mutation of Ubx results in the ectopic transcription of sca in the first abdominal segment. We propose that a direct interaction of Ubx with cis-acting elements in sca negatively regulates the gene. Transcript localization in several combinations of deficiencies in the Bithorax complex (BX-C) indicates that sca is downregulated by abdominal A (abdA) and Abdominal B (AbdB), and suggests that it is a common target of the three genes of BX-C. PMID- 1505522 TI - The extramacrochaetae gene provides information for sensory organ patterning. AB - The Drosophila adult epidermis displays a stereotyped pattern of bristles and other types of sensory organs (SOs). Its generation requires the proneural achaete (ac) and scute (sc) genes. In the imaginal wing disc, the anlage for most of the thoracic and wing epidermis, their products accumulate in groups of cells, the proneural clusters, whose distribution prefigures the adult pattern of SOs. These proteins then induce the emergence of SO mother cells (SMCs). Here, we show that the extramacrochaetae (emc) gene, an antagonist of the proneural function, is another agent that contributes to SO positioning. In the wing disc, emc is expressed in a complex and evolving pattern. SMCs appear not only within proneural clusters but also within minima of emc expression. When one of these spatial restrictions is eliminated, by ubiquitously expressing ac-sc, SMCs still emerge within minima of emc. When in addition, the other spatial restriction is reduced by decreasing emc expression, many ectopic SMCs emerge in a relatively even spaced and less constant pattern. Thus, the heterogeneous distribution of the emc product is one of the elements that define the positions where SMCs arise. emc probably refines SMC (and SO) positioning by reducing both the size of proneural clusters and the number of cells within clusters that can become SMCs. PMID- 1505523 TI - TAR-independent transactivation by Tat in cells derived from the CNS: a novel mechanism of HIV-1 gene regulation. AB - The Tat protein of human immunodeficiency virus type 1 (HIV-1) is essential for productive infection and is a potential target for antiviral therapy. Tat, a potent activator of HIV-1 gene expression, serves to greatly increase the rate of transcription directed by the viral promoter. This induction, which seems to be an important component in the progression of acquired immune deficiency syndrome (AIDS), may be due to increased transcriptional initiation, increased transcriptional elongation, or a combination of these processes. Much attention has been focused on the interaction of Tat with a specific RNA target termed TAR (transactivation responsive) which is present in the leader sequence of all HIV-1 mRNAs. This interaction is believed to be an important component of the mechanism of transactivation. In this report we demonstrate that in certain CNS-derived cells Tat is capable of activating HIV-1 through a TAR-independent pathway. A Tat responsive element is found upstream within the viral promoter that in glial derived cell lines allows transactivation in the absence of TAR. Deletion mapping and hybrid promoter constructs demonstrate that the newly identified Tat responsive element corresponds to a sequence within the viral long terminal repeat (LTR) previously identified as the HIV-1 enhancer, or NF-kappa B domain. DNA band-shift analysis reveals NF-kappa B binding activity in glial cells that differs from that present in T lymphoid cells. Further, we observe that TAR deleted mutants of HIV-1 demonstrate normal late gene expression in glial cells as evidenced by syncytia formation and production of viral p24 antigen.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1505524 TI - Cell cycle regulation of glucocorticoid receptor function. AB - Glucocorticoid receptor (GR) nuclear translocation, transactivation and phosphorylation were examined during the cell cycle in mouse L cell fibroblasts. Glucocorticoid-dependent transactivation of the mouse mammary tumor virus promoter was observed in G0 and S phase synchronized L cells, but not in G2 synchronized cells. G2 effects were selective on the glucocorticoid hormone signal transduction pathway, since glucocorticoid but not heavy metal induction of the endogenous Metallothionein-1 gene was also impaired in G2 synchronized cells. GRs that translocate to the nucleus of G2 synchronized cells in response to dexamethasone treatment were not efficiently retained there and redistributed to the cytoplasmic compartment. In contrast, GRs bound by the glucocorticoid antagonist RU486 were efficiently retained within nuclei of G2 synchronized cells. Inefficient nuclear retention was observed for both dexamethasone- and RU486-bound GRs in L cells that actively progress through G2 following release from an S phase arrest. Finally, site-specific alterations in GR phosphorylation were observed in G2 synchronized cells suggesting that cell cycle regulation of specific protein kinases and phosphatases could influence nuclear retention, recycling and transactivation activity of the GR. PMID- 1505525 TI - Cloning and functional characterization of the rat stomach fundus serotonin receptor. AB - A DNA segment homologous to the third exons of the serotonin 1C and 2 receptor genes was isolated from a mouse genomic library. The positions of the introns flanking these exons were conserved in the three genes. To examine whether the new fragment was part of an active gene, we used a quantitative PCR protocol to analyse rat RNAs from different tissues and ages. The gene was expressed in stomach fundus at an abundance of 1 x 10(5) mRNA molecules. This tissue contracts in response to serotonin via a receptor that has previously resisted classification. We constructed a cDNA library from rat stomach fundus and isolated clones containing 2020 bp inserts with open reading frames of 465 amino acids comprising seven putative membrane-spanning regions. The protein was transiently expressed in COS cells and binding of serotonergic ligands to the membranes was analysed. The pharmacological profile resembled that described for the serotonin-stimulated contraction of the stomach fundus. After expression of this receptor in Xenopus oocytes, the application of serotonin triggered the typical chloride current which presumably results from the activation of phospholipase C. The coupling to this response system was less efficient than that of the 5-HT1C or 5-HT2 receptors. PMID- 1505526 TI - Steroid hormone synthesis by a vaccinia enzyme: a new type of virus virulence factor. PMID- 1505527 TI - Assessment of the in vivo aneuploidy/micronucleus assay in mouse bone marrow cells with 16 chemicals. AB - Assessment of the in vivo aneuploidy/micronucleus Assay in bone marrow cells with 16 chemicals is described. This assay is based on the detection of kinetochores (KC) in micronuclei (MN) by antikinetochore-specific (CREST) antibodies. Among sixteen chemicals tested, six were known clastogens, three were known aneuploidy inducers, and the other seven were suspected spindle poisons. These chemicals were tested for their ability to induce micronuclei with kinetochore(s) in bone marrow cells of CD-1 mice. The majority of MN formed in bone marrow cells treated with aneuploidy-inducing agents contained kinetochore(s) which are considered to be formed from whole chromosomes or centric fragments, while in clastogen treated bone marrow cells, majority of them contained no kinetochore(s) which are considered to be formed from acentric chromosomal fragments. Classification of chemicals into either aneuploidy inducing agents or clastogens is based on the relative frequency of MN with and without KC, respectively. These results suggest that the in vivo aneuploidy/micronucleus assay has a great potential to identify aneuploidy-inducing agents. PMID- 1505528 TI - Cytogenetic effects of vincristine sulfate and ethylene dibromide in human peripheral lymphocytes: micronucleus analysis. AB - Micronuclei kinetics and persistence in mononucleated and binucleated human peripheral lymphocytes following short-term (4 hr) and continuous (until harvest) in vitro exposure to vincristine sulfate (VS) and ethylene dibromide (EDB) were studied. Lymphocytes were exposed to chemicals for various doses and harvested at different culture times. Micronucleus frequencies were scored in both mononucleated and binucleated cells on the same slide. VS-treated cells showed a significantly higher incidence of micronucleus in both mononucleated and binucleated cells than controls (P less than 0.01). The cells treated continuously with VS produced comparatively higher frequencies of micronucleated cells than those treated for 4 hr. Highest micronuclei frequencies were observed 24 hr after chemical treatment in both mononucleated and binucleated cells and decreased later with time. However, the micronucleus frequencies remained significantly higher than the controls even in the cells harvested at 144 hr. VS induced a large number of micronucleated cells with multiple micronuclei. VS also caused a severe decrease in nuclear division due to cytotoxic effect. Lymphocytes treated with EDB for 4 hr and continuously showed a statistically higher incidence of micronuclei in binucleated cells compared to the controls (P less than 0.05), whereas in mononucleated cells higher micronucleus frequencies were observed only in cultures treated continuously. Continuous presence of EDB induced both dose- and time-dependent increase of micronuclei in both mono- and binucleated cells (P less than 0.05). EDB induced relatively few multiple micronucleated cells in comparison with VS. EDB did not affect nuclear divisions even with continuous treatment. High micronucleus frequencies observed at 144 hr harvest following 4 hr treatment of both EDB and VS suggest the persistence of DNA damage in cells. These studies suggest that micronuclei kinetics in human peripheral lymphocytes depends on the genotoxic potentially and cytotoxicity of a genotoxicant. PMID- 1505529 TI - Comparison of rat liver parenchymal and nonparenchymal cells in the activation of promutagens. AB - While the liver consists of both parenchymal cells (PC) and nonparenchymal cells (NPC), virtually all studies on promutagen activation have been performed using PC. To evaluate the comparative roles of PC and NPC in promutagen activation, we cocultivated a cell line generally considered to have an insignificant level of xenobiotic metabolism, Chinese hamster ovary (CHO) cells, with either PC, NPC, or a combination of both. The mixed culture was treated with two promutagens: dimethylnitrosamine (DMN) and 3-methylcholanthrene (3-MC). The induction of 6 thioguanine resistant mutants was evaluated using the well-established CHO/hypoxanthine-guanine phosphoribosyl transferase (HGPRT) assay. Activation of promutagens, as indicated by an increase in mutant frequency in CHO cells, was observed only when the PC were present with the CHO cells during the treatment period. No activation was observed with NPC. Coculturing of PC and NPC yielded essentially the same results as PC alone. P-450 mixed function monooxygenase activity measured by the 7-ethoxycoumarin-O-deethylase assay further substantiates that PC had a significantly higher xenobiotic metabolism activity than NPC. Our study therefore indicates that PC, not NPC, are the major cell population in the liver responsible for the activation of promutagens. PMID- 1505530 TI - Structure-activity relationship of genotoxic polycyclic aromatic nitro compounds: further evidence for the importance of hydrophobicity and molecular orbital energies in genetic toxicity. AB - A quantitative structure-activity relationship (QSAR) has been formulated for 15 polycyclic aromatic nitro compounds acting on E. coli PQ37. Upon damage of DNA by these substances beta-galactosidase is induced and can be easily assayed colorimetrically, hence, this is a short-term test for mutagenicity. The QSAR (log SOSIP = 1.07 log P - 1.57 epsilon LUMO - 6.41) is strikingly similar to that found earlier with nitroaromatics acting in the Ames test (TA100) and differs significantly for that found using TA98 organisms. The QSAR brings out in a unique manner the underlying similarity in the two test systems. PMID- 1505531 TI - Human HPRT mutant database: software for data entry and retrieval. AB - We have developed a computer database containing information on over 1,000 human hypoxanthine guanine phosphoribosyl transferase (HPRT) mutants. Both published and unpublished data are present. The database itself is maintained in a dBASE format (.DBF) and we provide a set of programs to examine and extract information from the database. A program to input information into the database is also supplied. The database and programs are available directly from us or via remote FTP (file transfer protocol) using BITNET/INTERNET. All programs require an IBM compatible computer, the MS-DOS operating system (version 3.3 or greater), and a hard disk with about 5 megabytes of free disk space. The purpose of the database is 1) to allow investigators to contribute their HPRT mutants directly to the database in a standardized fashion, and 2) to allow access to the entire database with a set of programs that allows manipulation and extraction of data. For example, using our programs it is possible to i) order the database by base pair position, ii) examine only information regarding mutagenesis by a particular agent, iii) search for a particular author, iv) create a report which contains selected portions of the database, the report can be printed or saved as a file. The database will be updated every several months and distributed. PMID- 1505532 TI - Mutation spectrum of spontaneous frameshift revertants in yeast using double strand gap repair. AB - A mutation spectrum was constructed from a series of randomly isolated spontaneous His+ revertants of the frameshift mutant his4-38 in Saccharomyces cerevisiae. For each true revertant, a 438 bp region encompassing his4-38 on chromosome III was recovered into a shuttle vector by double-strand gap repair. Of the 45 independent His+ revertants sequenced, 44 were -1 base deletions and one revertant was a +2 base insertion. The -1 deletions exhibited a bimodal distribution. Of the bases encompassing the his4-38 region from +153-181, approximately 45% were not involved in a reversion event, although a -1 frameshift within this region will result in a viable His+ revertant. Approximately 49% of -1 events occurred within runs of 3 repeated bases. At these sites the strand-slippage model for frameshift mutation is supported. However, the -1 events occurring at sites of 2 repeated bases and the low frequency (2%) of +2 base insertions suggest that the transiently misaligned template model is a significant mechanism in reversion of his4-38. When the distribution of -1 events at repeated bases was discounted, a hotspot involving a -T at position +163 was resolved. PMID- 1505533 TI - DNA sequence analysis of spontaneous and N-ethyl-N-nitrosourea-induced hprt mutations arising in vivo in cynomolgus monkey T-lymphocytes. AB - The study of hprt mutations in cynomolgus monkey T-lymphocytes is part of our effort to understand the mechanisms of mutagenesis in vivo. This primate model allows us to study mutations and their kinetics at the molecular level under well controlled conditions using recently developed techniques for selection of mutant T-cells and polymerase chain reaction (PCR) amplification of hprt cDNA, which is directly sequenced. This is the first report of the sequence of the coding region of the cynomolgus monkey hprt gene and PCR/DNA sequence analysis of seven spontaneous mutant T-cell clones, as well as 23 mutant clones isolated 63 and 601 days after treatment with ethylnitrosourea (ENU, 77 mg/kg, intraperitoneal). cDNA was reverse transcribed from hprt mRNA directly from a lysate of about 2-4 x 10(3) cells, and a 700 bp fragment including the coding region was amplified by PCR and sequenced. Of the seven spontaneous mutants, only one point mutation (GC- --AT transition) was detected, and the other six failed to amplify by PCR, possibly due to functional deletions. Of the 14 mutant clones isolated 63 days after ENU treatment, nine base substitutions were detected in ten clones: four transitions (three AT----GC and one GC----AT) and five transversions (four AT--- TA and one AT----CG). Of the nine mutants isolated 601 days after ENU treatment, six single base substitutions were detected in six clones (five AT----TA and one AT----CG transversions), and one mutant had a large deletion or insertion. No changes were detected in three clones (one Day 63 and two Day 601 clones). In summary, only one of 15 single base substitutions isolated after ENU treatment was a GC----AT transition mutation and the rest were transitions and transversions at AT sites. PMID- 1505534 TI - Muscle sound and electromyogram spectrum analysis during exhausting contractions in man. AB - The changes in the soundmyogram (SMG) and electromyogram (EMG) frequency content during exhausting contractions at 20%, 40%, 60% and 80% of the maximal voluntary contraction (MVC) were investigated by the spectral analysis of the SMG and EMG detected from the biceps brachii muscles of 13 healthy men. The root mean squares (rms) of the two signals were also calculated. Throughout contraction the EMG rms always increased while this was true only at 20% MVC for the SMG. A marked decrease was detected at 60% and 80% MVC. With fatigue the EMG spectra presented a compression towards the lower frequencies at all exercise intensities. The SMG showed a more complex behaviour with a transient increase in its frequency content, followed by a continuous compression of the spectra, at 60% and 80% MVC, and a nearly stable frequency content at lower contraction intensities. This study suggested that different aspects of the changes in the motor unit's activation strategy at different levels of exhausting contractions can be monitored by SMG and EMG signals. PMID- 1505535 TI - Effect of carnitine loading on long-chain fatty acid oxidation, maximal exercise capacity, and nitrogen balance. AB - Carnitine has a potential effect on exercise capacity due to its role in the transport of long-chain fatty acids into the mitochondria for beta-oxidation, the export of acyl-coenzyme A compounds from mitochondria and the activation of branched-chain amino acid oxidation in the muscle. We studied the effect of carnitine supplementation on palmitate oxidation, maximal exercise capacity and nitrogen balance in rats. Daily carnitine supplementation (500 mg.kg-1 body mass for 6 weeks) was given to 30 rats, 15 of which were on an otherwise carnitine free diet (group I) and 15 pair-fed with a conventional pellet diet (group II). A control group (group III, n = 6) was fed ad libitum the pellet diet. Palmitate oxidation was measured by collecting 14CO2 after an intraperitoneal injection of [1-14C]palmitate and exercise capacity by swimming to exhaustion. After carnitine supplementation carnitine concentrations in serum were supranormal [group I, total 150.8 (SD 48.5), free 78.9 (SD 18.4); group II, total 170.9 (SD 27.9), free 115.8 (SD 24.6) mumol.l-1] and liver carnitine concentrations were normal in both groups [group I, total 1.6 (SD 0.3), free 1.2 (SD 0.2); group II, total 1.3 (SD 0.3), free 0.9 (SD 0.2) mumol.g-1 dry mass]. In muscle carnitine concentrations were normal in group I [total 3.8 (SD 1.2), free 3.2 (SD 1.0) mumol.g-1 dry mass] and increased in group II [total 6.6 (SD 0.5), free 4.9 (SD 0.9) mumol.g-1 dry mass].(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1505536 TI - The effect of a high carbohydrate diet on running performance during a 30-km treadmill time trial. AB - The purpose of the present study was to examine the influence of a high carbohydrate diet on running performances during a 30-km treadmill time trial. Eighteen runners (12 men and 6 women) took part in this study and completed a 30 km time trial on a level treadmill without modifying their food intake (trial 1). The runners were then randomly assigned to a control or a carbohydrate (CHO) group. The CHO group supplemented their normal diets with additional carbohydrate in the form of confectionery products during the 7 days before trial 2; the control group matched the increased energy intake of the CHO group by consuming additional fat and protein. The mean (SEM) carbohydrate intake of both groups was 334 (22) g before trial 1, after which the CHO group consumed 566 (29) g.day-1 for the first 3 days and 452 (26) g.day-1 for the remaining 4 days of recovery. Although there was no overall difference between the performance times for the two groups during trial 2, the CHO group ran faster during the last 5 km of trial 2 than during trial 1 [3.64 (0.24) m.s-1 vs 3.44 (0.26) m.s-1; P less than 0.05]. Furthermore, the 6 men in the CHO group ran the 30 km faster after carbohydrate loading [131.0 (5.4) min vs 127.4 (4.9) min; P less than 0.05], whereas there was no such improvement in times of the men in the control group.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1505537 TI - The effects of a reduced exercise duration taper programme on performance and muscle enzymes of endurance cyclists. AB - The influence of tapering on the metabolic and performance parameters in endurance cyclists was investigated. Cyclists (n = 25) trained 5 days.week-1, 60 min.day-1, at 75-85% maximal oxygen consumption (VO2max) for 8 weeks and were then randomly assigned to a taper group: 4D (4 days; n = 7), 8D (8 days; n = 6), CON (control, 4 days rest; n = 6), NOTAPER (non-taper, continued training; n = 6). Muscle biopsy specimens taken before and after training and tapering were analysed for carnitine palmityltransferase (CPT), citrate synthase, beta hydroxyacyl CoA dehydrogenase (HOAD), cytochrome oxidase (CYTOX), lactate dehydrogenase, glycogen and protein. Significant increases in VO2max (6%), a 60 min endurance cycle test (34.5%), oxidative enzymes (77-178%), glycogen (35%) and protein (34%) occurred following training. After the taper, HOAD and CPT decreased 25% (P less than 0.05) and 26% respectively, in the CON. Post-taper CYTOX values were different (P less than 0.05) for 4D and 8D compared with CON. Muscle glycogen levels were increased (P less than 0.05) after tapering in the 4D, 8D and CON, but decreased in NOTAPER. Similarly, power output at ventilation threshold was significantly increased in the 4D (27.4 W) and 8D (27 W) groups, but decreased (22 W) in the NOTAPER. These findings suggest that tapering elicited a physiological adaptation by altering oxidative enzymes and muscle glycogen levels. Such an adaptation may influence endurance cycling during a laboratory performance test. PMID- 1505538 TI - Exercise-induced hypoxemia in athletes: role of inadequate hyperventilation. AB - These experiments examined the exercise-induced changes in pulmonary gas exchange in elite endurance athletes and tested the hypothesis that an inadequate hyperventilatory response might explain the large intersubject variability in arterial partial pressure of oxygen (PaO2) during heavy exercise in this population. Twelve highly trained endurance cyclists [maximum oxygen consumption (VO2max) range = 65-77 ml.kg-1.min-1] performed a normoxic graded exercise test on a cycle ergometer to VO2max at sea level. During incremental exercise at VO2max, 5 of the 12 subjects had ideal alveolar to arterial PO2 gradients (PA aO2) of above 5 kPa (range 5-5.7) and a decline from resting PaO2 (delta PaO2) 2.4 kPa or above (range 2.4-2.7). In contrast, 4 subjects had a maximal exercise PA-aO2 of 4.0-4.3 kPa with delta PaO2 of 0.4-1.3 kPa while the remaining 3 subjects had PA-aO2 of 4.3-5 kPa with delta PaO2 between 1.7 and 2.0 kPa. The correlation between PAO2 and PaO2 at VO2max was 0.17. Further, the correlation between the ratio of ventilation to oxygen consumption vs PaO2 and arterial partial pressure of carbon dioxide vs PaO2 at VO2max was 0.17 and 0.34, respectively. These experiments demonstrate that heavy exercise results in significantly compromised pulmonary gas exchange in approximately 40% of the elite endurance athletes studied. These data do not support the hypothesis that the principal mechanism to explain this gas exchange failure is an inadequate hyperventilatory response. PMID- 1505539 TI - Pain, thermal sensation and cooling rates of hands while touching cold materials. AB - Hand cooling and resulting comfort and pain were studied in 12 subjects, while touching six different materials (polyurethane foam, wood, nylon, rustproof steel, aluminium, and temperature-controlled metal) which were initially at ambient temperature. This was done for three ambient temperatures (-10 degrees, 0 degree and 10 degrees C), after pre-exposure exercise or rest, with bare hands or while wearing gloves. The observed cooling curves were analysed as Newtonian cooling curves. The observed time constants appeared to be significantly related to the materials' contact coefficients, the presence of hand protection, the preceding activity, and the interaction between contact coefficient and the presence of hand protection. These parameters also allowed a good description of the time constant (r2 = 0.8) of the related cooling curves. Thermal and pain sensation could be described in terms of the local skin temperature, ambient temperature and hand protection. Equal pain and thermal levels were associated with lower temperatures of the back of the hand than of the contact side. The slightly painful condition was associated with a skin temperature of 16 degrees C for the back and 19 degrees C for the palm of the hand. The pain level appeared to be inversely related to cooling speed. Skin freezing occurred at higher skin temperatures when touching cold objects than when exposed to cold air as a result of reduced supercooling. The regression equations determined allowed calculations to be made of safety limits for hand cooling while in contact with a wide range of materials. PMID- 1505540 TI - One-handed load carrying--cardiovascular, muscular and subjective indices of endurance and fatigue. AB - A group of 5 women and 11 men walked on a treadmill, each carrying a weight in the right hand. In separate experiments, the mass was varied to give total exhaustion within 3 min, 5 min, 9 min, and 13 min. In additional experiments 50% and 25% of the masses leading to exhaustion after 5 min were used, and these were stopped after 16 min. Heart rate (fc) and systolic blood pressure (BPs) were measured noninvasively. There was a consistent increase in fc x BPs during the experiments leading to exhaustion, while steady-states were obtained in the nonexhausting trials. An electromyogram (EMG) was recorded with cutaneous electrodes over the flexor carpi ulnaris and flexor digitorum superficialis muscles and the number of zero crossings (ZC) of the EMG signal per time unit were analysed. As the subjects approached exhaustion, the number of ZC declined exponentially, reaching approximately 50% of their initial values. In the nonexhausting experiments, however, the decline was slower and less marked, and during the second half of the experiment the number of ZC increased again. Subjectively, endurance was underestimated by all the subjects. It was concluded that cardiovascular and muscle criteria of fatigue in carrying coincided. Prolonged carrying in one hand of more than 6 kg or 10 kg for young healthy women and men respectively should not be recommended, since it could lead to cardiovascular non steady-states and EMG signs of fatigue. PMID- 1505541 TI - Simulation of hand cooling due to touching cold materials. AB - A simple analytical model has been developed to simulate the cooling of the hands due to touching various types of cold material. The model consisted of a slab of tissue, covered on both sides with skin. The only active mechanism was the skin blood flow. The blood flow was controlled by body core temperature, mean skin temperature, and local hand temperature. The blood flowed along the palm before returning via the back of the hand. The control function was adapted from an earlier study, dealing with feet, but enhanced with a cold induced vasodilatation term. The palm of the hand was touching materials that were specified by conductivity and heat capacity. The hand was initially at a steady-state in a neutral environment and then suddenly grabbed the material. The resulting cooling curves have been compared to data from an experiment including six materials (foam, wood, nylon, steel, aluminium and metal at a constant temperature), three temperatures (-10, 0, and 10 degrees C), two thermal states of the body (neutral and 0.4 degrees C raised), and with and without gloves. There was a fair general agreement between the model and the experiment but the model failed to predict three specific effects: the unequal effect of equal 10 degrees C steps in cold surface temperature on the temperature of the palm of the hand, the cooling effect of nylon, and the rapid drop in back of the hand temperature. Nevertheless the overall regression was 0.88 with a standard deviation between model and experiment of about 2.5 degrees C. PMID- 1505542 TI - Glucose and free fatty acid utilization during prolonged exercise in prepubertal boys in relation to catecholamine responses. AB - Ten prepubertal boys performed 60-min cycle exercise at about 60% of their maximal oxygen uptake as previously measured. To measure packed cell volume, plasma glucose, free fatty acids (FFA), glycerol and catecholamines, blood samples were drawn at rest using a heparinized catheter and at the 15th, 30th and 60th min of the exercise and after 30 min of recovery. At rest, the blood glucose concentrations were at the lowest values for normal. Exercise induced a small decrease of blood glucose which was combined with an abrupt increase of the noradrenaline concentration during the first 15 min. The FFA and glycerol concentrations increased throughout the exercise linearly with that of adrenaline. Compared to adults, the FFA uptake expressed per minute and per litre of oxygen uptake was greater in children. These results suggested that it is difficult for children to maintain a constant blood glucose concentration and that prolonged exercise provided a real stimulus to hypoglycaemia. An immediate and large increase in noradrenaline concentration during exercise and a greater utilization of FFA was probably used by children to prevent hypoglycaemia. PMID- 1505543 TI - Cardiovascular responses in paraplegic subjects during arm exercise. AB - The purpose of this study was to examine cardiovascular responses during arm exercise in paraplegics compared to a well-matched control group. A group of 11 male paraplegics (P) with complete spinal cord-lesions between T6 and T12 and 11 male control subjects (C), matched for physical activity, sport participation and age performed maximal arm-cranking exercise and submaximal exercise at 20%, 40% and 60% of the maximal load for each individual. Cardiac output (Qc) was determined by the CO2 rebreathing method. Maximal oxygen uptake was significantly lower and maximal heart rate (fc) was significantly higher in P compared to C. At the same oxygen uptakes no significant differences were observed in Qc between P and C; however, stroke volume (SV) was significantly lower and fc significantly higher in P than in C. The lower SV in P could be explained by an impaired redistribution of blood and, therefore, a reduced ventricular filling pressure, due to pooling of venous blood caused by inactivity of the skeletal muscle pump in the legs and lack of sympathetic vasoconstriction below the lesion. In conclusion, in P maximal performance appears to have been limited by a smaller active muscle mass and a lower SV despite the higher fc,max. During submaximal exercise, however, this lower SV was compensated for by a higher fc and, thus at the same submaximal oxygen uptake, Qc was similar to that in the control group. PMID- 1505544 TI - Peak power output predicts maximal oxygen uptake and performance time in trained cyclists. AB - The purposes of this study were firstly to determine the relationship between the peak power output (Wpeak) and maximal oxygen uptake (VO2max) attained during a laboratory cycling test to exhaustion, and secondly to assess the relationship between Wpeak and times in a 20-km cycling trial. One hundred trained cyclists (54 men, 46 women) participated in the first part of this investigation. Each cyclist performed a minimum of one maximal test during which Wmax and VO2max were determined. For the second part of the study 19 cyclists completed a maximal test for the determination of Wpeak, and also a 20-km cycling time trial. Highly significant relationships were obtained between Wpeak and VO2max (r = 0.97, P less than 0.0001) and between Wpeak and 20-km cycle time (r = -0.91, P less than 0.001). Thus, Wpeak explained 94% of the variance in measured VO2max and 82% of the variability in cycle time over 20 km. We concluded that for trained cyclists, the VO2max can be accurately predicted from Wpeak, and that Wpeak is a valid predictor of 20-km cycle time. PMID- 1505545 TI - Heart rate overshoot at the beginning of muscle exercise. AB - A characteristic notch in the heart rate (fc) on-response at the beginning of square-wave exercise is described in 7 very fit marathon runners and 12 sedentary young men, during cycle tests at 30% and 60% of maximal oxygen consumption (VO2max). The fc notch revealed a fc overshoot with respect to the fc values predicted from exponential beat-by-beat fitted models. While at 30% of VO2max all subjects showed a fc overshoot, at 60% of VO2max it occurred in the marathon runners but not in the sedentary subjects. The mean time of occurrence of the fc overshoot from the onset of the exercise was 16.7 (SD 4.7) s and 12.2 (SD 3.2) s at 30% of VO2max in the runners and the sedentary subjects respectively, and 23.8 (SD 8.8) s at 60% of VO2max in the runners. The amplitude of the overshoot, with respect to rest, was 41 (SD 12) beats.min-1 and 31 (SD 4) beats.min-1 at 30% of VO2max in the runners and the sedentary subjects respectively, and 46 (SD 19) beats.min-1 at 60% of VO2max in the runners. The existence and the amplitude of the fc overshoot may have been related to central command and muscle heart reflex mechanisms and thus may have been indicators of changes in the balance between sympathetic and parasympathetic activity occurring in fit and unfit subjects. PMID- 1505546 TI - Psycho-sensorimotor performance in divers exposed to six and seven atmospheres absolute of compressed air. AB - In the present study, we investigated the psycho-sensorimotor abilities of divers exposed to 6 ATA (50 m of sea water; corresponding to legal limit for occupational diving in North America, United Kingdom, and Northern Europe), or 7 ATA (60 m; the legal limit in France and Southern Europe) of compressed air (1 ATA = 100,000 Pa), using psychometric tests of manual dexterity, visual choice reaction time, and number ordination. The results of the present study showed that abilities in these tests were not significantly altered by pressure exposure to 6 ATA of compressed air. However, data obtained at 7 ATA showed slight but significant decreases in performance. Nevertheless, a few subjects presented large decreases in performance ranging from -20% to -25% of control. Finally, our results supported the ergonomic point of view that the laws limiting occupational diving to 6 ATA (50 m) are better adapted to reality and the requirements of underwater activity. PMID- 1505547 TI - D-lactate concentrations in blood, urine and sweat before and after exercise. AB - The purpose of this study was to investigate changes in the concentrations of D lactate, L-lactate, pyruvate and methylglyoxal (MG) in body fluids after exercise. Eight untrained male students and five male students who were boat club members engaged in the exercise. Each subject performed runs of short and long duration. Compared to pre-exercise values plasma concentrations of D-lactate, L lactate and pyruvate increased after running; in trained men by 3.6, 5.0, 3.4 times after short runs and by 1.5, 4.6, 2.0 times after long runs, and in untrained men by 3.0, 12.0, 1.6 times after short runs and 2.5, 5.6, 1.6 times after long runs, respectively. In all cases, the increase of L-lactate was always higher than that of D-lactate after running. The MG contents in red blood cells decreased markedly after running, especially in the untrained students. After short runs the MG concentration had decreased to 13% in the untrained men and 30% in the trained men, and after long runs the concentration had decreased to 41% in the untrained and 60% in the trained men. The MG in plasma and red blood cells appeared to have been utilized during relatively anaerobic exercise, especially by the untrained subjects. The D-lactate and related substances were also determined in urine, but the concentration of these substances showed no relationship to exercise. The D-lactate concentration in sweat samples tripled after short periods of running but the relative concentration to sodium ion concentration was not altered.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1505549 TI - Stress Doppler echocardiography using dobutamine in coronary patients with and without ischaemia induction. AB - To examine the effects of dobutamine on pulsed-Doppler left ventricular ejection dynamics and its utility for evaluation of coronary disease (CAD) we studied 10 patients with normal coronaries (Group 1) and 24 patients with significant CAD (greater than or equal to 70% diameter stenosis) using a graded stress infusion (5 to 20 micrograms.kg-1.min-1). Two-dimensional echocardiography was performed to detect regional asynergy and analysed using an 11-segment model. Patients with CAD were divided into those with (Group 3, n = 14) and without (Group 2, n = 10) inducible ischaemia; six patients had reversible involvement of greater than or equal to three segments (subset 3A). Groups were well matched for baseline left ventricular function and all studies were carried out while the patients were not taking cardioactive therapy. Hyperkinetic wall motion was typical and exaggerated hyperkinesis of normal segments was commonly seen in those with baseline (n = 9) or reversible asynergy (n = 14). Normals and CAD patients showed comparable changes in heart rate and blood pressure (P = NS between groups).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1505548 TI - Venous responses to rhythmic exercise in contralateral forearm and calf. AB - Ten normal healthy subjects performed a rhythmic handgrip at 30% MVC (maximal voluntary contraction) with and without arterial occlusion of the same limb. Contralateral forearm and calf venous capacitance were simultaneously measured by venous occlusion plethysmography. During rhythmic handgrip at 30% MVC contralateral venous capacitance decreased by -7.17% in the forearm and by -5.14% in the calf. With arterial occlusion the decreases in venous capacitance were even more pronounced: contralateral forearm -14.4% and calf -13.1%. In a second set of experiments (n = 5) rhythmic handgrip at 30% MVC with arrest of the forearm circulation 5 s prior to the cessation of contraction was applied to examine the influence of chemically sensitive metaboreceptors per se on the evoked limb venoconstriction. During the postexercise arterial occlusion forearm venous volume decreased further to -30.6% whereas calf venous volume increased slightly but remained below the control value. After the cessation of the arterial occlusion both forearm and calf capacitance returned to baseline values. Thus, this study provided evidence that as well as a chemically generated reflex arising from the working muscle, central command was found to be involved in the increase in venomotor tone in the nonexercising limbs during rhythmic handgrip at 30% MVC. PMID- 1505550 TI - Improved monitoring of myocardial ischaemia during major vascular surgery using transoesophageal echocardiography. AB - As regional wall motion abnormality (RWA) is the first sign of ischaemia, transoesophageal echocardiography was evaluated as a monitoring device in 51 patients undergoing abdominal aortic surgery. Wall motion of the entire left ventricular wall (nine segments) was semiquantitatively evaluated 15 min before and after aortic cross-clamping and 3 h after declamping. In addition, limb lead II of the electrocardiogram was simultaneously recorded. At baseline, RWA was present in 16 patients (31%). New or worsened RWA 15 min after aortic cross clamping was seen in 17 patients, of whom 11 had persistent RWA, i.e. it was still present 3 h after declamping. This was associated in seven patients with enzymatically documented myocardial infarction. Only one infarct patient demonstrated ST segment changes of more than 1 mm. Thus, a single electrocardiographic surface lead is insensitive for perioperative myocardial ischaemia detection. Furthermore, new and/or worsened RWA after aortic cross clamping, which persists until 3 h after declamping, is, to a considerable degree, associated with perioperative infarction. PMID- 1505551 TI - Non-invasive assessment of mitral stenosis before and after percutaneous balloon mitral valvotomy by Doppler continuity equation. AB - The continuity equation was used to estimate non-invasively the stenotic mitral valve area by comparison with two other echocardiographic methods (planimetry and pressure half-time) and with Gorlin's formula as the gold standard. The accuracy of the equation of continuity was determined before and 24 h after valvuloplasty in a study group of 21 patients with severe mitral stenosis. According to the equation of continuity, mitral valve area was calculated by the product of the cross-sectional area and the aortic or pulmonary annulus and the ratio of the time velocity integral of the aortic or pulmonary flow to that of the mitral stenotic jet. In pre-valvotomy basal conditions, the Doppler continuity equation demonstrated significant correlations with 2D planimetry (r = 0.72, P less than 0.01), with the pressure half-time method (r = 0.62, P less than 0.01) and with the Gorlin formula (r = 0.66, P less than 0.01). There was no significant difference between the haemodynamic data and the echocardiographic measurements. Twenty-four hours after valvotomy, the Doppler continuity equation also demonstrated significant correlations with 2D planimetry (r = 0.83, P less than 0.01), with pressure half-time (r = 0.82, P less than 0.01) and with the Gorlin formula (r = 0.69, P less than 0.01). However, the haemodynamic measurements significantly overestimated (P less than 0.01) the echographic measurements. Thus, we conclude that the continuity equation provides an accurate estimation of mitral valve area in mitral stenosis before and after balloon valvotomy. PMID- 1505552 TI - Arterial elastic properties in man: a comparison of echo-Doppler indices of aortic stiffness. AB - Non-invasive assessment of mechanical properties of the aorta may prove useful in the early detection of atheroma. We have evaluated several of the available echocardiographic indices using ability to detect age-related changes in putatively disease-free vessels as a measure of sensitivity to changes in aortic mechanical properties. Suprasternal imaging was used in 49 healthy non-smoking volunteers to measure minimum and maximum aortic arch diameters. Maximal flow velocities, with corresponding acceleration times and heart periods, were determined in the descending aorta in 24 of these subjects. Blood pressure was recorded non-invasively immediately after the echocardiographic study. Doppler derived measurements of aortic flow acceleration did not relate to age (P greater than 0.05). Three different 2D echo assessments of aortic distensibility, however, all showed a close relationship to age. Ep elastic modulus and Beta index (derived from different stress-strain mechanical relationships) were significantly related to age with r = 0.69 and 0.65 respectively. There were no significant effects of gender or left ventricular systolic function on these relationships. There was a tendency for the relationship between these distensibility indices and age more closely to fit an exponential than a linear relationship. We conclude that 2D echocardiographic assessment of aortic distensibility is able to detect sensitively changes in aortic mechanical properties. Even in the absence of risk factors for cardiovascular disease there is a marked reduction in aortic distensibility with increasing age. PMID- 1505553 TI - The effects of thrombolytic therapy on the high-resolution electrocardiogram after myocardial infarction. AB - The effects of thrombolytic treatment was studied in 109 consecutive patients 9 11 days after their first acute myocardial infarction by high-resolution electrocardiography (ECG), 24 h Holter monitoring, exercise test and radionuclide ventriculography. Thirty-seven patients were treated with intravenous thrombolytic agents. Thrombolytic treatment was assessed by clinical criteria to be successful in 22 patients and probably successful in 12 patients. Thrombolysis failed in three patients and 72 patients did not receive thrombolytic treatment (control group). Measurements made on the high-resolution and filtered (60 Hz high-pass) vectormagnitude complex included the total duration, the duration of the potential less than 40 microV, the root mean square (RMS) voltage in 10 ms intervals over the first 50 ms and RMS voltage of the last 40, 50 and 60 ms. The filtered QRS duration was significantly shorter in reperfused patients compared with the control group (83 +/- 10 vs 89 +/- 12 ms; P = 0.017). In inferior infarcts (n = 57) the filtered QRS duration was 83 +/- 11 ms in reperfused and 89 +/- 10 ms in non-reperfused patients (P = 0.044), but in anterior infarcts (n = 52) there was no difference. The RMS voltage of the initial 50 ms of the QRS was higher in the reperfused than in non-reperfused anteroseptal infarcts (38 +/- 14 v 23 +/- 10 microV; P = 0.022). Patients successfully treated with thrombolytic agents within the first 2 h had higher RMS voltage of the terminal 40 ms of the QRS than patients treated within 2-4 h (38 +/- 17 vs 27 +/- 17 microV; P = 0.03).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1505554 TI - Exercise habits and physical performance during comprehensive rehabilitation after coronary artery bypass surgery. AB - The effects of training as part of a comprehensive rehabilitation programme on exercise capacity and habits was studied in 171 male coronary artery bypass surgery patients randomized into a rehabilitation (R) (n = 93) and a reference, hospital-based treatment (H), group (n = 78). The rehabilitation programme started with a 2-day informative course before surgery and continued with a 3 week exercise-based course 2 months after surgery followed by a 2-day refresher 8 months post-operatively. The percentages of subjects having regular exercise were 22% and 10% pre-operatively, 42% and 38% 6 months and 46% and 38% 12 months after surgery in the R and H groups, respectively. The changes in the proportions observed in R and H groups were not significantly different. Total work during a bicycle exercise test increased from 38.9 +/- 24.3 kJ pre-operatively to 64.0 +/- 31.4 kJ 6 months (P less than 0.001) and to 70.0 +/- 35.7 kJ 12 months (P less than 0.001) post-operatively in group R and from 40.8 +/- 25.6 kJ to 57.3 +/- 26.6 kJ (P less than 0.001) and to 60.4 +/- 30.8 kJ (P less than 0.001) in group H, respectively. The increase from the pre-operative value was greater in group R than in group H both 6 (P = 0.03) and 12 months (P = 0.02) after surgery. Respective changes occurred in maximal work load, but the increase was significantly greater in group R than in group H only 12 months post operatively.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1505555 TI - Improvement in left ventricular function after rapid weight loss in obesity. AB - The effect of rapid weight reduction on left ventricular function and blood pressure was studied in 34 obese subjects, who all weighed more than 30% above their ideal body weight. Subjects with co-existing hypertension (N = 15) and proven coronary artery disease (N = 9) were included to assess contributions from these factors. Blood pressure (BP) was measured both indirectly and by direct ambulatory intra-arterial methods. Radionuclide ventriculography was performed at rest and at exercise, before and after dieting, which was supervised in hospital (daily intake 330 kCal day-1 for 4 weeks). Dieting induced a weight loss of (mean +/- SD) 9.6 +/- 3.5 kg (P less than 0.0001) in the whole group. The mean daytime intra-arterial blood pressure fell from 157 +/- 23/90 +/- 15 to 144 +/- 21/85 +/- 13 mmHg (P less than 0.0001). The fall in ambulatory intra-arterial diastolic blood pressure did not reach significance in the normotensive and ischaemic groups. The mean resting left ventricular ejection fraction (LVEF) in the whole group showed a significant reduction after weight loss from 61 +/- 10% to 56 +/- 6% (P less than 0.005). Although the individual groups showed a fall in LVEF, the effect was most marked in the hypertensive group, from 65 +/- 9% to 57 +/- 5% (P less than 0.002). Before dieting none of the groups achieved a 'normal' 5% rise in LVEF above basal in response to exercise, the hypertensive and the ischaemic groups both showing non-significant falls. This phenomenon was, however, reversed after weight loss.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1505556 TI - Left ventricular filling pattern and pulmonary wedge pressure are closely related in patients with recent anterior myocardial infarction and left ventricular dysfunction. AB - To determine whether mitral flow velocity can be used to estimate mean pulmonary wedge pressure (PWP) in patients with left ventricular dysfunction, 50 patients with recent Q-wave anterior infarction and a reduced ejection fraction (less than 40%) underwent simultaneous pulsed-wave Doppler measurements of mitral flow and right heart catheterization. Doppler tracings and PWP were recorded at rest, after passive leg lifting (45 degrees) and (in 15 patients with increased PWP) after 5 mg sublingual ISDN. Significant correlations were found between the ratio of peak early to peak late diastolic velocity (E/A) and PWP (r = 0.83). Early diastolic deceleration and the ratio of the time velocity integral of atrial contribution to the total time velocity integral were also correlated to PWP (r = 0.80 and r = 0.79 (respectively). The E/A ratio was less than 1 in 25 patients and more than 1 in the remaining 25. An E/A ratio of at least 1 predicted a PWP of more than 20 mmHg with a sensitivity of 100% and a specificity of 86%. In all five patients, in whom the PWP was less than 20 mmHg at baseline and became greater with leg lifting, the E/A ratio changed from less than 1 to more than 1. After ISDN, changes in E/A ratio from more than 1 to less than 1 identified all 12 patients with a PWP falling below 20 mmHg. In conclusion, patients with recent Q-wave anterior infarction and a reduced ejection fraction mitral flow velocity derived variables correlate with PWP representing a reliable index for the diagnosis of markedly increased PWP.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1505557 TI - Congenital complete heart block associated with QT prolongation. AB - The coexistence of congenital complete heart block and QT prolongation represents a special type of arrhythmia. The electrophysiological and clinical characteristics of this syndrome were studied in eight patients suffering from congenital AV block and QT prolongation. Data from 22 patients suffering from congenital complete heart block only, served as a control. In the study group, the appearance of a torsade de pointes type of ventricular tachycardia could regularly be observed and the tachycardial attack could usually be provoked by ventricular extrastimuli. The corrected QT time was markedly prolonged; on ventricular stimulation, at higher pacing rates the QT interval shortened, but remained significantly higher than in the control group. Syncopal attacks--with the character of polymorphic tachycardia--appeared in each patient of the study group while occurring in only three patients from the control group. Patients were given pacemaker implants (using a higher pacing rate) and long-term administration of beta-receptor blockers. The outcome was favourable; no ventricular tachycardia or syncopal attack was observed in the follow-up period. PMID- 1505558 TI - Blood pressure changes during the game of squash. AB - The extent and pattern of the blood pressure response to the playing of squash was studied in five healthy volunteers using intra-arterial blood pressure recordings. Systolic pressure increased more than diastolic, but by only 18% of basal, peaking 5.2 +/- 2.3 min into the game (mean game duration 49 +/- 4 min). Thereafter there was a progressive decline, with reducing pulse pressure towards basal. There was a marked and significant increase in beat-by-beat blood pressure variability (P less than 0.01) and systolic peaks of up to 200 mmHg were recorded. A peak heart rate of 171 +/- 25 beats min-1 occurred at 20 min. These findings do not support the concept of a disproportionate and prolonged pressor response induced by playing squash. The possibility of high single-beat systolic peaks still justifies some caution in subjects at risk of arterial rupture. PMID- 1505559 TI - Heart rate correction based on 'universal' regression equation--erroneous conclusions when studying cardiac mechanical function during stress. AB - This paper studies the possible errors associated with the use of a 'universal' regression equation in heart rate correction when used on mechanical cardiac function parameters. Systolic time interval rate correction, using Weissler regression equations, is taken as an example. The measurements were made during the isometric handgrip test, the orthostatic test, the Valsalva manoeuvre and the cold pressor test. It was observed that in most measurements rate correction caused a significant correlation between the changes in heart rate and the rate corrected systolic time interval. It is considered that this new dependence between heart rate and the rate-corrected parameter makes the physiological interpretation of results more difficult. Therefore it is recommended that in stress provocations mechanical cardiac function parameters should not be rate corrected by methods based on a 'universal' regression equation between heart rate and the mechanical function parameter. PMID- 1505560 TI - A double-blind, parallel-group comparison of flosequinan and enalapril in the treatment of chronic heart failure. AB - The effects of flosequinan and enalapril on exercise capacity (bicycle exercise duration), quality-of-life symptomatology (visual analogue scales) and New York Heart Association (NYHA) grading, were compared in 61 patients with chronic heart failure (NYHA, grade III). Bicycle exercise duration improved similarly with flosequinan (+27%) and enalapril (+18%); in patients completing the study, flosequinan produced a significantly greater increase in exercise time at week 12, compared with enalapril (P = 0.02). Improvements in visual analogue scores relating to general health, energy and vitality, ability to perform physical activities and breathing performance, were equivalent for both drugs. Changes in NYHA classification showed that 27 (55%) of 49 patients completing the study had improved by at least one NYHA grade (15 (68%) patients on flosequinan; 12 (44%) on enalapril). The overall safety and tolerability of the two treatments was similar; 18 patients reported adverse effects while on flosequinan, compared with 19 patients on enalapril. Neither treatment was associated with any clinically important changes in haematological or biochemical variables, although some treatment-related effects were observed. This study confirms that flosequinan achieved similar efficacy to enalapril in the symptomatic relief of chronic heart failure. The effect of flosequinan on survival in chronic heart failure has not been tested; pending such studies, our data suggest that it may prove a useful alternative therapy in patients where ACE inhibitors are contraindicated or poorly tolerated. PMID- 1505561 TI - Myocardial protection during percutaneous transluminal coronary angioplasty: effects of trimetazidine. AB - Trimetazidine (TMZ) has recently been shown to improve anginal symptoms without altering haemodynamic variables. A randomized, double-blind, placebo-controlled study was conducted in 20 patients to study the effects of TMZ on the severity of myocardial ischaemia during PTCA of the left anterior descending coronary artery. Five minutes after a first successful dilatation (D0), a control balloon inflation (D1) was performed until onset of ischaemic signs on both the intracoronary (i.c.) and precordial ECG. Two minutes later, patients received either TMZ 6 mg or placebo i.c. Another inflation (D2) was performed 5 min after D1. No differences were found between the two groups regarding responses in heart rate, systemic and i.c. pressures during the study. TMZ decreased the maximum ST segment shift at D2 compared with D1 (0.8 +/- 0.1 vs 1.4 +/- 0.3 mV, P = 0.023) and delayed its onset (46 +/- 4 vs 36 +/- 5 s, P = 0.024). TMZ also decreased maximum T-wave changes (1.06 +/- 0.24 vs 2.19 +/- 0.3 mV, P = 0.001), and significantly reduced the area under the curve (mv s-1) of the i.c. ST-segment and T-wave changes during balloon inflation (P = 0.042 and P = 0.009 respectively). The placebo had no effect on these parameters. These results support the hypothesis that trimetazidine has a direct anti-ischaemic effect on human myocardial cells. PMID- 1505562 TI - Electrophysiological and haemodynamic effects of lidocaine and ajmaline in the management of sustained ventricular tachycardia. AB - The electrophysiological and haemodynamic effects of lidocaine (100 mg) and ajmaline (50 mg) were evaluated while attempting to interrupt sustained ventricular tachycardia. The study was performed as a prospective, non-blinded, randomized investigation in 61 patients. Lidocaine terminated ventricular tachycardia in four of 31 patients, ajmaline in 19 of 30 patients (P less than 0.001). QRS and RR intervals during ventricular tachycardia were prolonged by ajmaline from 164 +/- 28 ms to 214 +/- 49 ms and from 371 +/- 86 ms to 479 +/- 137 ms (P less than 0.001), respectively; lidocaine did not influence these parameters. The duration of the return cycles after termination of ventricular tachycardia did not differ between the two groups. Lidocaine did not change cardiac output during ventricular tachycardia whereas cardiac output increased significantly under ajmaline from 3.5 +/- 1.21.min-1 to 5.5 +/- 1.91.min-1 (P less than 0.001). It is concluded that anti-arrhythmic agents such as ajmaline, which slow conduction velocity and prolong refractoriness, are more effective than lidocaine in the medical treatment of haemodynamically stable, sustained ventricular tachycardia. PMID- 1505563 TI - Effect of benazepril on myocardial ischaemia in patients with chronic stable angina pectoris. AB - The anti-ischaemic properties of benazepril, a non-sulfhydryl inhibitor of angiotensin-converting enzyme, were assessed in 20 patients with chronic stable angina pectoris, by repeated exercise tests and repeated 72-h ambulatory electrocardiographic monitoring. The study was a double-blind, placebo-controlled cross-over; 11 patients received benazepril 10 mg b.i.d. and nine received 20 mg b.i.d. All patients had a positive treadmill stress test and at least three ischaemic episodes during 24 h of ambulatory electrocardiographic monitoring. Benazepril at a dose of 10 mg b.i.d. did not improve the exercise duration, the time taken to reach 1 mm ST depression. Similar findings were observed during treatment with 20 mg b.i.d. Benazepril at a dose of 10 mg b.i.d. was ineffective in improving ischaemic parameters during daily activities. However, among the nine patients who received 20 mg b.i.d. the number of ischaemic episodes was reduced from 142 to 103, and the total duration of ischaemic was reduced from 1099 to 531 min. The number of weekly anginal attacks was reduced from 58 to 33, and the weekly sublingual nitroglycerin tablets consumption was reduced from 31 to 14. When the two doses (10 mg and 20 mg) were combined (N = 20), the number of ischaemic episodes was reduced from 314 to 260 (P = 0.074), and the duration of ischaemic was reduced from 3453 to 2514 min (P = 0.072). PMID- 1505564 TI - Regression of structural vascular changes in hypertensives after captopril treatment. AB - In order to investigate whether hypertension-related structural vascular changes may be influenced by antihypertensive treatment, 10 patients were studied suffering from essential arterial hypertension, five males and five females, aged between 34 and 61 years (mean age: 46.9 +/- 8.13 years). All patients received a placebo for 1 week and then captopril, 75 mg b.i.d. for 3 months. After placebo and captopril treatments, the following parameters were evaluated: SBP, DBP, mean blood pressure (MBP), by the formula 1/3 (SBP + 2 x DBP) and basal and minimal vascular resistances, respectively obtained by the ratios MBP/rest flow and MBP/peak flow. Blood flows have been obtained by strain gauge plethysmography. A significant decrease in systolic (P less than 0.025), diastolic (P less than 0.01) and mean blood pressure (P less than 0.01), basal vascular resistances (52 +/- 19 vs 28 +/- 12 A.U., P less than 0.01) and minimal vascular resistances (6.3 +/- 2.2 vs 3.9 +/- 2.8 A.U., P less than 0.025) has been observed after captopril treatment in comparison to placebo, whereas rest (2.9 +/- 0.7 vs 4.1 +/- 0.9 ml.min-1.100 g-1, P less than 0.01) and peak blood flows (21.3 +/- 5.8 vs 29.7 +/ 9.4 ml.min-1.100 g-1) significantly increased. These data seem to indicate that antihypertensive treatment with the angiotensin-converting enzyme inhibitor, captopril, is not only efficacious in inducing a significant blood pressure decrease, consequent to the reduction of basal vascular resistance (due to the vasodilating effects of the drug), but is also able to reduce minimal vascular resistance.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1505565 TI - Clinical significance of silent ischaemia and implications for treatment: role of radionuclide techniques. AB - Radionuclide techniques have added substantial information to aid detection and heighten the clinical significance of silent ischaemia. While non-invasive assessment of myocardial perfusion, metabolism and wall motion have increased the knowledge of the pathophysiology of silent ischaemia, radioisotope techniques may provide information far beyond that obtained by electrocardiographic criteria alone. Whether patients with silent ischaemia should be treated can only be inferred from indirect evidence suggested by preliminary trials. Only randomized, controlled, clinical trials will yield the definite answers as to the effects of treatment on clinical outcome. PMID- 1505566 TI - Intra-operative contrast echocardiography in coronary artery disease. AB - Intra-operative echocardiography is becoming a reference standard for the evaluation of the results of cardiac surgery. Myocardial contrast echocardiography has been recently introduced to study regional myocardial blood flow and cardioplegia distribution in patients undergoing coronary artery surgery. It can be used in three different stages: before cardiopulmonary bypass, to identify the most hypoperfused myocardial segments; during cardioplegic arrest, to check the adequacy of myocardial protection; postoperatively, to assess graft patency. The priority in revascularization can be assigned according to the regional perfusion pattern, which depends not only on coronary artery narrowing, but also on the extent of collateral circulation. The distribution of cardioplegia to the myocardium can be monitored in real time with clear identification of poorly protected myocardial segments. The injection in the graft after weaning from cardiopulmonary bypass allows assessment of graft patency and measurement of the 'area at risk' for graft occlusion. In conclusion, the information obtained in the operating theatre by myocardial contrast echocardiography is original and promises to have a significant impact on surgical strategy. Implementation of the ultrasonic equipment to obtain quantitative on-line data on myocardial blood flow is desirable. PMID- 1505567 TI - Luis Morquio (1867-1935). PMID- 1505569 TI - Doppler and 2D echocardiographic diagnosis of congenital coronary artery fistulae to the right cardiac chambers: report of 3 cases. AB - We present three cases of coronary artery fistulae to the right cardiac chambers. The first was a 2-day-old neonate in congestive heart failure: 2D and Doppler echocardiography revealed a dilated proximal left coronary artery and a fistulous connection to the right atrium. The other two patients, respectively 4 and 3 years old, were asymptomatic and presented with a continuous heart murmur: a left coronary artery fistula into the right ventricle was detected by ultrasound in one, and a dilated proximal right coronary artery in the other. The diagnosis was confirmed in all three patients. The first patient was operated upon at 18 months of age; the second patient is awaiting surgery, and in the third patient the fistula was ligated at the age of 3 years. The possibility of ultrasound diagnosis without invasive procedures is suggested. PMID- 1505568 TI - Peripheral ischaemia and gangrene presenting at birth. AB - The aetiology of non-iatrogenic causes of peripheral ischaemia and gangrene presenting either at birth or within a few hours of delivery is unknown in the majority of 56 confirmed cases. In this review of 47 cases occurring since 1941 the aetiology was clear in only 6, four due to compression by the encircling umbilical cord. There was no clear association with gestational age, birth weight, maternal age or type of delivery. Seven were infants of poorly controlled diabetic mothers and these may constitute a subgroup due to altered haemostatic mechanisms. Pregnancy hypertension was an association in 7 cases, oligohydramnios in 6. There is only limited support for birth trauma, sepsis, and thrombo-emboli from the ductus arteriosus as causes. There is indirect evidence that thrombo emboli can migrate from the placental bed to the fetus. In recent years death from this condition has been rare with surgical thrombectomy increasingly successful in late presenting cases. When gangrene is established at birth surgical amputation, autoamputation, or some loss of function is usual. Peripheral ischaemic insults presenting at birth may be part of a wider spectrum of disorders, both prenatal and perinatal, attributable to occlusive vascular disruption. PMID- 1505570 TI - Intellectual capacity of subjects exposed to methimazole or propylthiouracil in utero. AB - Antithyroid drugs, considered the treatment of choice for hyperthyroidism during pregnancy, may have an adverse effect on intellectual development of the offspring. We examined the intellectual capacity of 31 subjects aged 4-23 years, born to women with Graves disease who received antithyroid drugs throughout pregnancy. Methimazole 40-140 mg/week (n = 15) or propylthiouracil 250-1400 mg/week (n = 16) was given. I.Q. was assessed using the Wechsler test appropriate for age. Twenty-five unexposed siblings served as controls. The exposed and unexposed groups did not differ with respect to the total I.Q. Both groups scored equally in verbal and performance skills and in each of six main subcategories of the tests. There was no difference between exposure to methimazole and propylthiouracil or between the higher (greater than 40 mg/week and greater than 600 mg/week, respectively) and lower dosages. All children were euthyroid at birth and none had goitre. We conclude that exposure to methimazole or propylthiouracil during pregnancy in doses sufficient to control maternal hyperthyroidism does not pose any threat to intellectual capacity of the offspring. PMID- 1505571 TI - Recurrent abdominal pain of gastro-intestinal origin. AB - A consecutive series of 71 children (mean age 8.6 years) with recurrent abdominal pain underwent endoscopic oesophageal, gastric and duodenal biopsy in order to determine whether the pain was of gastro-intestinal origin. Of these 71 children, 27 (38%) showed oesophagitis, 14 (20%) cardiac gastritis, 29 (41%) body gastritis, 38 (54%) antral gastritis, and 29 (41%) duodenitis. Thus, 66 of the 71 children studied had an inflammatory lesion explaining their complaints. One of the patients had a gastric ulcer. Helicobacter pylori colonisation was found in 5 of the children: One had H. pylori associated antral and body gastritis and 4 H. pylori associated antral gastritis only. Body gastritis without H. pylori was present in three of these four children. Our data do not support the widespread assumption that recurrent abdominal pain for which no medical cause can be found, is psychogenic; neither do they establish an association between H. pylori antral gastritis and recurrent abdominal pain. However, our data provide strong evidence that there is a gastro-intestinal origin of these patients' complaints. PMID- 1505572 TI - Hypergalactosaemia and portosystemic encephalopathy due to persistence of ductus venosus Arantii. AB - Hypergalactosaemia was discovered in a newborn girl during routine metabolic screening. Hereditary enzyme deficiency was ruled out. Because hypergalactosaemia persisted, an open ductus venosus Arantii was suspected but remained undetected by conventional two-dimensional ultrasonography. It was demonstrated by combined colour and pulsed wave Doppler sonography. At age 3 years 6 months, the girl developed initial symptoms of portosystemic encephalopathy which progressed and was treated by protein restriction, oral lactulose and flumazenil, with some success. In the absence of enzyme deficiency, hypergalactosaemia in the newborn is an early sign of duct persistence. For the unambiguous diagnosis of an open duct, colour Doppler sonography is the method of choice. Pulsed wave Doppler sonography is recommended for pathophysiological characterisation of the splanchnic venous return. PMID- 1505573 TI - Patent ductus venosus with hypoplastic right hepatoportal system in a young child born with asymmetric intra-uterine growth retardation. AB - We report a functioning ductus venosus with hypoplasia of the right hepatoportal system in a 2-year-old child born with asymmetric intra-uterine growth retardation. Postprandial galactosaemia and hyperammonaemia were clues to diagnosis of portal-systemic shunt through the patent ductus venosus, which was confirmed by ultrasonography and angiography. PMID- 1505574 TI - Patency of the ductus venosus and disease. PMID- 1505575 TI - Atypical Kawasaki disease: an often missed diagnosis. AB - We describe four patients with vasculitis of the coronary and other medium sized arteries. Three of them died as a consequence of cardiac failure and the fourth had a ruptured aneurysm of the left common iliac artery. Coronary vasculitis is pathognomonic for Kawasaki disease (KD), but our patients had few other signs of this disorder, suggesting so called atypical KD. Because the described patients lacked most of the clinical criteria, the diagnosis was delayed. We focus on other clinical features in these patients and stress the importance of early recognition and treatment. PMID- 1505576 TI - Systemic lupus erythematosus: a case report with unusual manifestations and favourable outcome after plasmapheresis. AB - We report a case of systemic lupus erythematosus (SLE) in a 15-year-old girl with severe neurological disease, platelet function disorder and pulmonary haemorrhage, which remitted after plasmapheresis. The patient developed protein losing enteropathy shrinking lung, and acute pancreatitis with pseudocyst formation. These infrequent complication of SLE are discussed. PMID- 1505577 TI - McKusick-Kaufman syndrome: the diagnostic challenge of abdominal distension in the neonatal period. AB - We report a newborn girl with McKusick-Kaufman syndrome who presented at birth with severe life-threatening abdominal distension due to hydrometrocolpos. In children with polydactyly and cystic masses in the lower abdomen should hydrometrocolpos be especially considered. Ultrasonography is of great value in the correct assignment of lower abdominal tumours, but should be completed by vagino(cysto)scopy when hydrometrocolpos is suspected. PMID- 1505578 TI - Robinow syndrome in two siblings from consanguineous parents. AB - A Kurdish family had two children affected with Robinow syndrome. The daughter had short stature, macrocephaly, hypertelorism, hepatosplenomegaly, short forearms and marked vertebral anomalies. Her brother had hypertelorism, hypertrophied alveolar ridges, hepatosplenomegaly, short forearms, rib anomaly and ambiguous genitalia. The karyotype of the affected male sibling showed mosaicism for 45X, 46,X,dicY(q11.22), 47,X,dicY(q11.22),dicY(q11.22). PMID- 1505579 TI - Salla disease variant in a Dutch patient. Potential value of polymorphonuclear leucocytes for heterozygote detection. AB - A Dutch child with psychomotor retardation, impaired speech, ataxia, sialic acid storage and vacuolized skin fibroblasts and lymphocytes was diagnosed as having free sialic acid storage disease. Slight corneal opacities, pale optic disks at the fundus oculi and vertebral abnormalities, not earlier reported in Salla disease, were peculiar to this case. Free sialic acid was about tenfold increased in urine and cultured fibroblasts, without changes in the glycoconjugate-bound sialic acid pool. A subsequent pregnancy of the patient's mother was monitored by assay of sialic acid in chorionic villi and amniotic fluid. An unaffected foetus was predicted. Sialic acid was also assayed in peripheral blood total leucocytes, and in mononuclear and polymorphonuclear (PMN) leucocyte subpopulations. Each of these leucocyte fractions from the patient showed 10- to 30-fold increase in sialic acid content. The PMN subpopulation provided the most restricted range of control values and showed slightly increased values for the patient's parents. These results suggest that the assay of sialic acid in PMN might be useful for the identification of heterozygotes in sialic acid storage disease. Studies on a larger number of obligate heterozygotes are needed to confirm this observation. PMID- 1505580 TI - Surfactant protein A in the course of respiratory distress syndrome. AB - Surfactant-associated protein (SP-A) was measured in tracheal aspirates of ventilated infants with (n = 51) and without (n = 21) respiratory distress syndrome (RDS). SP-A concentrations in samples collected after birth were significantly lower in RDS than in infants ventilated for other reasons than RDS (median 0.03 vs. 1.60 micrograms/ml). As a biochemical test to diagnose RDS early after birth, the sensitivity of measuring SP-A in tracheal aspirates was 87% and specificity 81%. SP-A content in tracheal aspirates of infants with RDS was monitored during the first 7 days of life. A significant (P less than 0.001) increase within the first 4 days was found in those infants who survived, whereas no such change was found in those infants who died. PMID- 1505581 TI - Benign infantile familial convulsions. AB - Five infants, three girls and two boys, first had convulsions between the ages of 4 and 6 months. Although the aetiology of the attacks was unknown, all the infants had a family history of similar convulsions occurring at the same age and having a benign outcome. The attacks, which always occurred in a cluster, were promptly controlled, in four cases with phenobarbital and in one case with valproate. Seizures were partial with secondary generalization and were characterized by head and eye deviation (not always the same side in each attack) diffuse hypertonia and then bilateral limb jerks. The interictal EEG was normal. The ictal EEG showed diffuse discharge with onset in the central-occipital region. Laboratory, radiological and neurological findings were normal. A history in at least one paternal relative (the father in four cases) of similar seizures, occurring at the same age suggested a genetic predisposition. No seizures or EEG anomalies were observed during the follow up. PMID- 1505582 TI - Benefits and risks of fluoride supplementation: caries prevention versus dental fluorosis. AB - To assess the risks (dental fluorosis) and the benefits (caries prevention) of fluoride (F) tablets and F toothpaste, we surveyed 2003 schoolchildren aged 5-20 years old (mean = 10.82, SD = 3.40). Children were scored for dental caries by means of the decayed, missing, filled teeth index (DMFT index). Frequent use of F toothpaste (toothbrushing frequency) is poorly linked to caries (Spearman r = 0.05, P = 0.02) and dental fluorosis (r = 0.05, P = 0.03). Children who use F tablets regularly and appropriately exhibit mild fluorosis more often than non- or occasional users (odds ratio = 9.58), and have a mean DMFT index 50% lower than other children. We conclude that using F tablets is an effective means of preventing caries. When used appropriately in non fluoridated areas, using F tablets results in minor damage. PMID- 1505583 TI - Fatal pancytopenia during high-dose valproate monotherapy. PMID- 1505584 TI - Acute phosphorus intoxication in very low birth weight infant. PMID- 1505585 TI - Prenatal diagnosis of Canavan disease. PMID- 1505586 TI - Dystonic attacks related to sleep and exercise. AB - Two unrelated children displayed attacks of paroxysmal jerky 'puppet-like' movements lasting 2-3 min. The attacks were not kinesigenic and occurred during wakefulness precipitated by physical exercise and during NREM sleep, spontaneous or upon arousal and awakenings. Paroxysmal dystonic choreoathetosis was excluded by the absent family history, and paroxysmal kinesigenic dystonia by the absence of triggering effects by sudden movements and efficacy of anticonvulsants. Pattern and duration of involuntary movements were not those typical of nocturnal paroxysmal dystonia. Our cases emphasize that overlap exists among the different clinical categories of paroxysmal dyskinesia. PMID- 1505587 TI - Enumeration of T, B and natural killer peripheral blood cells of patients with multiple sclerosis and controls. AB - The median percentages of peripheral blood immunoglobulin-positive (Ig+) lymphocytes (8%, n = 46), CD8+ (12%, n = 49) and CD57+ cell numbers (5%, n = 37) of patients suffering from multiple sclerosis (MS) were significantly (p less than 0.05) lower than the values of age- and sex-matched healthy individuals (Ig+ cells: 13%, n = 46; CD8+ cells: 17%, n = 49; CD57+ cells: 9%, n = 37). Comparison of calculations on decreased peripheral blood cell counts and increased brain cell counts in MS patients revealed that sequestration of blood cells into the MS brain is a possible explanation of these findings. PMID- 1505588 TI - Polymerase chain reaction analysis for specific HTLV-1 sequences from cerebrospinal fluid and peripheral blood cells in Sardinian multiple sclerosis patients. AB - Using polymerase chain reaction and specific primers, we found no gag and env sequences of HTLV-1 in DNA samples from peripheral blood mononuclear cells of 26 multiple sclerosis (MS) patients with relapsing-remitting, relapsing-progressive and progressive course from onset of the disease, and from 8 patients affected with other neurological diseases (OND). A Positive signal for the gag region was found in DNA samples from cerebrospinal fluid mononuclear cells (CSFMC) of 6/17 (27.3%) MS patients (either with relapsing-remitting, or relapsing-progressive and progressive course from onset of the disease), and in 2/11 (18.2%) CSFMC OND samples. Positive hybridization for the env sequence was evident in 2/11 (18.2%) CSFMC from OND and none of MS samples. The finding of positive hybridization for gag and env sequences in a few samples of CSFMC may be related to the presence in the CSF of a great number of activated cells, which could express cross-reacting sequences of endogenous retrovirus. PMID- 1505589 TI - Does the severity of leukoaraiosis contribute to senile dementia? A comparative computerized and positron emission tomographic study. AB - The present study evaluates the origin, severity and location of leukoaraiosis in senile dementia and in normal ageing. The regional white-matter lucency scores, determined on computed-tomographic scan of the brain, are compared to the regional blood flow, oxygen extraction rate and oxygen consumption, determined by the [15O] steady-state technique with positron emission tomography. Thirty patients, classified according to the presence or absence of leukoaraiosis and their mental status, are examined. The occurrence and severity of dementia appear to be mainly correlated to decreased blood flow and oxygen metabolism in the frontal, temporal and parietal cerebral cortex. Leukoaraiosis in demented and nondemented patients is associated with lowered blood flow in the frontal and parietal white matter. The regional lucency score is increased, and blood flow and oxygen consumption decreased in the frontal white matter of severely demented patients. Frontal leukoaraiosis contributes to dementia and is probably of ischemic origin, while parietal and occipital leukoaraiosis is due to wallerian degeneration. PMID- 1505590 TI - Intracranical aneurysm and cerebral embolism. AB - Embolism from the aneurysmal sac is a rare but possible manifestation of intracranial aneurysm; thrombus formation is probably related to the combined action of turbulent flow and a 'stagnant zone'. Three cases are presented: 2 with giant aneurysms (1 internal carotid and 1 sylvian) and 1 with a large aneurysm of the middle cerebral artery. In the latter, surgical treatment was performed, while in the others a conservative therapy was preferred. No ischemic manifestations were observed in the follow-up. PMID- 1505591 TI - Periventricular plaques in multiple sclerosis: irreversible? An MRI follow-up study. AB - Follow-up MRIs over a period of 2-3 years in 50 patients with multiple sclerosis demonstrate that, in contrast to the circumscribed nonperiventricular lesions of the cerebral white matter, the periventricular plaques only show a remission in exceptional cases as ovoid lesions adjacent to the pars centralis of the lateral ventricles. 90% of the patients exhibited at least one new or enlarged nonperiventricular lesion. 72% had more pronounced periventricular lesions in the second scan. With the help of serial MRIs, inferences can be drawn about the histopathological stage of individual demyelination plaques. PMID- 1505592 TI - Dorsolateral pontine hemorrhage producing pure sensory stroke. AB - Pure sensory stroke predominantly results from lacunar infarction in the posteroventral nucleus of the thalamus. We report the history of a young nonhypertensive male presenting with pure sensory stroke due to hemorrhage of a small arteriovenous malformation in the dorsolateral part of the pons. In contrast to the extent of the lesion, only minor degree of objective sensory loss was observed. Furthermore, our observation is unique in that it is the first presentation of this syndrome with that particular location. PMID- 1505593 TI - Sphenoid sinus mucocele with recurrent visual disturbance. AB - We present a case of sphenoid sinus mucocele with recurrent visual disturbance on the same side. A 22-year-old female showed two episodes of visual disturbance in the left eye for 3 months, and acute retrobulbar optic neuritis was diagnosed. With corticosteroid, visual disturbance improved in 1 week. MRI and CT scans showed mucocele in the left sphenoid sinus, and left optic nerve swelling with high intensity was observed in T2-weighted MRI. No destruction of the optic canal was found. The contiguous inflammation in the optic nerve rather than compression was considered as pathogenesis. PMID- 1505594 TI - Structural brain correlates of neurologic abnormalities in multiple sclerosis. AB - We examined the relationship between cerebral magnetic resonance imaging (MRI) findings and urinary dysfunction in 70 consecutive patients with definite multiple sclerosis. MRI-weighted lesion scores for seven different brain regions were recorded according to the number and size of cerebral lesions. Thirty-two subjects (46%) had urinary symptoms and 38 (54%) were asymptomatic. Subjects with urinary symptoms exhibited greater overall functional disability and a higher midbrain MRI-weighted lesion score than asymptomatic patients. No statistically significant group differences were found for the other brain regions. PMID- 1505595 TI - Acute measles encephalitis of the delayed type: neuroradiological and immunological findings. AB - A case of delayed acute measles encephalitis in an immunosuppressed child is reported. Detailed immunological studies have shown defective humoral immunity (defective IgA, IgG2 and IgG3) and decreased natural killer activity. Neuroradiological examination by magnetic resonance imaging revealed several high signal lesions on T2-weighted images in the gray matter without clinical or pathological correlation. The implications of these findings are discussed. PMID- 1505596 TI - Congenital basilar impression: correlated neurological syndromes. AB - A series of 8 cases operated on for symptomatic basilar impression associated with occipitalization of the atlas is reported (with or without atlantoaxial dislocation). Symptoms of onset (such as the frequent association between nuchal pain and vertigo) are emphasized and analyzed in relation to the pathogenetic mechanism that underlies the multiform symptomatology of the basilar impression. The diagnostic workup for basilar impression foresees X-rays, magnetic resonance imaging and computed tomography. The most important diagnostic problem is that of considering the possible existence of such a pathology in the presence of very common symptoms such as nuchal pain and vertigo. The surgical treatment has certainly been useful both to improve and to stabilize the symptomatology mainly when there is atlantoaxial dislocation. In fact in these cases the symptomatology is more severe and progressive for the alteration of the transverse ligament of the atlas secondary to abnormal mechanical stimuli. PMID- 1505597 TI - Protective effect of low-grade hypothermia in experimental skeletal muscle ischemia. AB - In the present study, a rat hindlimb tourniquet model was used to investigate the effect of moderate hypothermia on ischemic muscle necrosis. Complete circulatory arrest was maintained for 4.5 h. During the ischemic period the animals were kept in an infant incubator at different temperatures. After 72 h survival the percentage of necrosis in the anterior tibial muscle was measured morphometrically on histological slides. At an ambient temperature of 24 degrees C there was 80% necrosis in the anterior tibial muscle. At 22 degrees C the necrosis was reduced to 29%. This reduction corresponds to more than 30 min shortening of the ischemia time. Differences in tissue temperature may explain some of the discrepancies reported in tolerance limits for muscle ischemia. To achieve consistent results in experimental muscle ischemia, it is necessary to control the ambient temperature. PMID- 1505598 TI - Acetic acid-induced colitis in the rat: a reproducible experimental model for acute ulcerative colitis. AB - There exists no ideal model for experimental ulcerative colitis in common laboratory animals. Therefore, we tried in the present study to establish a reproducible model for inducing colitis in rats by using acetic acid. A blind loop of the colon including the cecum, ascending colon and part of the transverse colon, was brought out through two colostomies. After mechanical washing with warm normal saline, acetic acid was instilled at different doses (4, 6 and 8%) for different exposure times (10, 15, 20, 25 and 30 s). The excluded colon was examined by light microscopy on the 1st, 2nd, 3rd, 4th, 7th and 14th days after operation and acetic acid instillation. We found that 4% acetic acid for 15 s produced a moderate, superficial colitis on the 1st day after operation, whereafter a uniform colitis evolved in all rats on the 4th day after operation. The developed colitis showed morphological similarities with human ulcerative colitis. Signs of healing and regeneration of the mucosa were seen on the 7th day, and the mucosa became almost normal at the 14th day after operation. 6 or 8% acetic acid solution or exposure times exceeding 15 s resulted in severe, deep colitis with a concomitant high mortality rate. In contrast, at exposure times less than 15 s, acetic acid induced only mild superficial colitis. We conclude that by using 4% acetic acid for 15 s in the excluded colon a uniform and reproducible colitis pathologically resembling human ulcerative colitis could be achieved. Furthermore, no mortality was encountered and the general health of the rats was similar to that of the controls.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1505599 TI - Influences of ciclosporin pretherapy on 90% hepatectomized rats. AB - We studied the effect of ciclosporin (Cs) on rats which underwent a 90% hepatectomy. Rats were divided into two groups: group 1 (without Cs pretreatment) and group 2 (with Cs pretreatment). Animals were given a 4-day treatment of Cs (10 mg/kg/day) prior to hepatectomy. The 1-week survival, serum biochemistry and parameters for hepatocyte proliferation (indices for mitosis and 5-bromo-2 deoxyuridine uptake) were serially investigated. Although Cs pretherapy significantly upregulated liver cell proliferation in group 2, there was no improvement in the survival rate of the immunosuppressed animals (group 2) compared to the controls (group 1). The implications of Cs pretherapy are discussed in the setting of extensive hepatectomy. PMID- 1505600 TI - Adriamycin combined with hyperthermia and dipyridamole is cytotoxic both in vitro and in vivo. AB - The cytotoxicity of adriamycin (ADM) combined with hyperthermia (Hyp) and/or dipyridamole (DP) was investigated using B16 melanoma cells in vitro and in vivo. When ADM was combined with Hyp at 43 degrees C or DP in a dose of 5 microM or with both, drug cytotoxicity enhanced the inhibition of colony formation and cell growth, and the effect was maximal when Hyp and DP were combined. Incubation with DP alone for 24 h, following ADM exposure, enhanced the toxicity even further (p less than 0.01). Measurement of intracellular levels of ADM in the B16 melanoma cells showed that Hyp and DP increased accumulation of ADM, and that DP, but not Hyp, significantly suppressed the ADM excretion (p less than 0.05). Growth of B16 melanoma implanted into subcutaneous tissue of the foot of C57BL mice was inhibited to a greater extent by the combination treatment of ADM and DP, ADM and Hyp, and also that of ADM, Hyp and DP, compared to the findings in cases of ADM or Hyp alone. As this trimodality treatment is effective both in vitro and in vivo, further study on possible clinical advantage is warranted. PMID- 1505601 TI - Lack of correlation between the acute haemodynamic response to intravenous captopril and plasma concentrations of angiotensin II in patients with chronic cardiac failure. AB - We have given a series of incremental intravenous injections of captopril to ten patients with chronic cardiac failure. Small doses of captopril produced significant changes in pulmonary artery end-diastolic pressure and right atrial pressure, up to a total cumulative dose of captopril of 2.5 mg, after which further injections had no significant effect. There were large changes in systemic vascular resistance and blood pressure up to a cumulative dose of captopril of 5.0 mg, after which the injection of larger doses caused no further significant changes. Small doses of intravenous captopril produced large increases in plasma renin activity and plasma angiotensin I concentrations up to a total cumulative dose of captopril of 1.25 mg, after which there were no significant further changes in either plasma renin activity or plasma angiotensin I concentration. However the plasma concentration of angiotensin II fell more slowly, no further change being recorded after a total cumulative dose of captopril of 10 mg. These results suggest that plasma renin activity is not the only determinant of plasma angiotensin II concentrations. PMID- 1505602 TI - Comparison of plasma and synovial concentrations of synthetic salmon calcitonin after a single intravenous dose. AB - The plasma and synovial fluid concentrations of synthetic salmon calcitonin in 10 patients with knee joint effusions have been compared after a single i.v. dose of 200 I.U. calcitonin. Plasma and synovial fluid concentrations of calcitonin were measured using a specific RIA before and 30 and 60 min after administration. Calcitonin was not detectable at zero time in plasma or in synovial fluid. Plasma calcitonin concentrations 60 min after administration were significantly lower than at 30 min, while the synovial fluid concentration remained relatively constant. The results show that synthetic salmon calcitonin penetrates into the articular cavity after a single i.v. dose of 200 I.U. and that a steady concentration persists there over 60 min. PMID- 1505603 TI - Pharmacokinetics of ofloxacin in elderly patients and in healthy young subjects. AB - The pharmacokinetics of ofloxacin, a fluoroquinolone widely used in the treatment of bacterial infections, may be different according to age, owing to the biological differences that exist between an elderly organism and a young subject, especially as regards the renal and the hepatic function. In our study the pharmacokinetics of ofloxacin in 12 elderly patients was found to be different from those of 12 healthy young volunteers. The elimination half-life (t1/2) was slightly shorter in the young subjects than in the elderly: 6.2 (0.9)h against 8.5(1.2)h respectively. The oral total clearance was lower in the geriatric patients compared to the young healthy volunteers: 83.3(16.6) ml/min in the first group, and 23.3(33.3) ml/min in the second group. AUC and peak plasma concentration in elderly exceeded those noted in young healthy volunteers. The results of this study suggest that, compared with younger subjects, older patients experience delayed elimination of ofloxacin. It would be reasonable, from a pharmacokinetic point of view, to limit the dose of ofloxacin in patients more than 75 years old, at least to one half of that given to younger patients. PMID- 1505604 TI - Constant K+/Na+ excretion ratio during peak diuresis after piretanide but insignificant K+ loss during 24 hours. AB - The effect of piretanide on Na+ and K+ excretion and on renal haemodynamics has been studied in 14 subjects with a GFR (Inulin clearance) ranging from 140 to 2 ml.min-1. After a two day fluid and salt balance control period, oral piretanide 6 mg induced a natriuresis and kaliuresis, which was proportional to the GFR of the patients. The ratio of drug-induced K+ to Na+ excretion was always 0.13, independent of individual GFR. This was only true for the duration of the action of piretanide, tau, which was 6 h in subjects with normal GFR and 5 h in patients with impaired kidney function. Surprisingly, after tau, i.e. for 24 h after drug administration, less potassium was lost than in the pretreatment period. Neither the GFR nor the renal blood flow (PAH clearance) of the patients were affected by piretanide. In conclusion, piretanide given once a day was an effective natriuretic agent, even in end-stage renal disease, and it produced relatively little K(+)-loss when given once daily. PMID- 1505605 TI - Computer assisted design of a theophylline dosing regimen in acute bronchospasm: serum concentrations and clinical outcome. AB - The effect of intravenous theophylline on the outcome of inhospital treatment of acute bronchospasm has been assessed, comparing the results achieved by computer assisted dosing, designed to achieve and maintain a serum theophylline level of 16 micrograms.ml-1 (10 patients) with those of unaided physicians (15 control patients). The outcome measures compared were clinical improvement, peak expiratory flow rate and serum theophylline concentration. Loading doses of theophylline in the control and computer groups were: 167 and 437 mg, respectively. Initial serum theophylline concentrations, measured 20 min after the loading dose, were 13.6 and 17.0 micrograms.ml-1 in the control and computer groups, respectively. In patients who had not received theophylline prior to admission, loading doses and initial concentrations were: 200 mg and 9.4 micrograms.ml-1 in the control group (n = 5) versus 613 mg and 15.7 micrograms.ml 1 in the computer group (n = 4), respectively. During maintenance therapy, serum theophylline concentrations were kept in the therapeutic range (10-20 micrograms.ml-1) throughout 51% and 77% of the hospitalisation period, in the control and computer groups, respectively. There were no differences between the two groups in the rate or extent of clinical improvement or in change in peak expiratory flow rate. The computer assisted theophylline dosing regimen outperformed that of the unaided physicians in achieving and maintaining therapeutic serum theophylline concentrations in acute bronchospasm. There was no correlation between clinical outcome and serum theophylline concentration, but this may have been due to the small sample size and modest difference in serum theophylline between the two groups.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1505606 TI - The effect of three different oral doses of verapamil on the disposition of theophylline. AB - Results of previous studies suggest that the theophylline-verapamil drug interaction may be dependent on verapamil dose. Therefore, in a randomized four way cross over study, 12 healthy males received theophylline, as a single intravenous dose of aminophylline, alone (phase I) and after a four day regimen of oral verapamil 40 mg (phase II), 80 mg (phase III), and 120 mg (phase IV) every 8 h. Serial blood samples were collected over a 24 hour period for determination of serum theophylline concentration and subsequent pharmacokinetic analysis. Mean theophylline AUC for phase I-IV was 93.6, 105.6, 110.8, 120.1 mg.h.l-1, respectively. Mean theophylline clearance for phase I-IV was 3.89, 3.59, 3.35, and 3.20 l.h-1, respectively. The changes in AUC, clearance, and lambda z were linearly correlated to verapamil dose. These results suggest that the inhibitory effect of verapamil on the pharmacokinetic disposition of theophylline is directly related to verapamil dose. PMID- 1505608 TI - Change in glucose metabolism after long-term treatment with deflazacort and betamethasone. AB - We have compared the long-term effects of different corticosteroids on glucose metabolism by carrying out a 75 g oral glucose tolerance test in 27 subjects before and after the administration of deflazacort or betamethasone for two months in random balanced sequence. Fasting plasma glucose and insulin concentrations were significantly higher after betamethasone, whereas deflazacort increased only fasting plasma insulin. After oral glucose there were significant increases in blood glucose and insulin after betamethasone compared with deflazacort. These results suggest that the degree of glucose intolerance and insulin resistance depends on the steroid used and on the dose given, although long-term treatment with deflazacort has a smaller effect on glucose metabolism than betamethasone. PMID- 1505607 TI - Nicardipine does not cause deterioration of glucose homoeostasis in man: a placebo controlled study in elderly hypertensives with and without diabetes mellitus. AB - The effect of the calcium antagonist nicardipine on insulin secretion and glucose homoeostasis was investigated in elderly hypertensives with and without diabetes mellitus; 15 patients with essential hypertension for at least 10 years and normal glucose tolerance according to standard criteria (Group I) and 15 elderly hypertensive patients affected by Type 2 diabetes mellitus and on treatment with diet or oral drugs (Group 2). In the basal state, all patients were submitted to an oral glucose tolerance test (OGTT, 75 g) and an iv arginine test (30 g), on two different days and in random order. The same tests were repeated after one month of treatment with nicardipine 60 mg/day, in three spaced doses, the last being given 1 h before the post-treatment test. Nicardipine did not change overall glucose homoestasis, as assessed by haemoglobin Alc and fructosamine, nor did it significantly affect the plasma insulin response either to glucose or arginine in Groups 1 and 2. Only the glucagon response to arginine was significantly reduced in diabetic hypertensives. Small, non-significant variations in the metabolic and hormonal parameters were seen in additional two groups of patients (Groups 3 and 4), matched with Groups 1 and 2 for age, sex and diseases, who took capsules containing placebo. Thus, nicardipine did not produce any significant overall alteration in glucose homoestasis when given to elderly diabetic or nondiabetic hypertensive subjects. PMID- 1505609 TI - Modeling the pharmacokinetics and pharmacodynamics of dexamethasone in depressed patients. AB - Changes in time course effected by cortisol suppression and the relationship of these changes to the plasma dexamethasone concentration of suppressor and non suppressor patients are described in this report on a combined pharmacokinetic pharmacodynamic model. Thirteen depressed patients (8 suppressors and 5 non suppressors) received an intravenous dose (1.5 mg) of dexamethasone. The drug induced effect changes are found to lag behind, in time, the plasma drug level changes. To accurately relate the temporal relationship of effect changes to plasma dexamethasone levels, a pharmacodynamic model (sigmoid-Emax) was combined with a pharmacokinetic model that incorporated an effect compartment. The magnitude of the time-lag was quantified by the half-time of equilibration between concentrations in the hypothetical effect compartment and the plasma dexamethasone levels (t1/2keo). The t1/2keo of the nonsuppressing group was about 50% of that of the suppressing group, indicating that for a given plasma level the onset and termination of effect for the nonsuppressing group is about two times more rapid than for the suppressing group. Moreover, the model can estimate the effect-site concentration that causes one-half of the maximal predicted effect (EC50), a measure of an individual's sensitivity to dexamethasone. The receptor sensitivity (as determined from the EC50 ratio) of the suppressing group was about twice that of the nonsuppressing group. PMID- 1505611 TI - Methods for testing impairment of driving due to drugs. AB - The Transport and Road Research Laboratory has been concerned for a long time with possible causes of driving difficulties and has developed methods for investigating driving performance. The question addressed here was how applicable these methods are in assessing driving problems arising from the use of drugs which can impair performance, particularly widely-available centrally-acting drugs. We assessed four types of driving-related tests by comparing their sensitivities with two laboratory tests, developed elsewhere, which measure more basic effects of drugs on performance, using drugs known to impair skills. Performances under the influences of ethanol, the benzodiazepine lorazepam, and the antihistamine triprolidine, each given both as a single high dose and a single low dose, were compared with performances after placebo. We used double blind crossover design, in which subject variability was minimized by studying only women of a limited age range (45-55 y). The driving-related tests detected the effects of the substances used, although they were generally less sensitive than the laboratory tests. The individual sensitivities of the driving test could be improved to match those used for more general assessments. PMID- 1505610 TI - Long-term nicotine substitution after application of a 16-hour nicotine patch in smoking cessation. AB - The purpose of the study was to examine long-term nicotine substitution and its variability during use of a nicotine patch. In two smoking cessation studies a 16 h nicotine patch, releasing 15 mg nicotine, was applied daily for 16 h over 12 weeks, to 167 smokers. Salivary cotinine was highly correlated with plasma cotinine (r = 0.93), and the concentration of cotinine in a single sample in the afternoon was well correlated with the AUCcontinine over 24 h (r = 0.94). The salivary cotinine concentration after 1 week in 60 abstainers was 183 ng.ml-1. After 3,6 and 12 weeks the cotinine concentrations were 86%, 79% and 59% of the 1 week value. The degree of nicotine compensation attained by the patch after 1 week was 52% (SD 24%) in subjects who succeeded in stopping smoking for at least 3 weeks. A quarter of the subjects achieved a compensation of less than 35% of their usual nicotine intake. Nicotine substitution with this 16-h nicotine patch was stable and the risk of overcompensation was small in this group of smokers. PMID- 1505612 TI - Evaluation of the accuracy of a pharmacokinetically-based patient-controlled analgesia system. AB - Bone marrow transplant patients having severe, prolonged oral mucositis pain (expected to last for one to three weeks) used a computer-controlled infusion system to self-administer morphine for pain control. Individual patient pharmacokinetic information, derived from a pretreatment bolus morphine dose, was used in a new bolus-elimination transfer algorithm to produce rapid adjustments of steady plasma morphine concentrations when the patient requested more or less drug. We evaluated the performance characteristics (bias and precision) of this pharmacokinetically based patient-controlled analgesic infusion system (PKPCA) in a group of 15 cancer patients over six to 14 days. Although we found a three- to fivefold pharmacokinetic variability in the tailoring morphine dose data, the PKPCA system was free of systematic bias (insignificant overall prediction error) during the patient-controlled infusions in this study population. The absolute prediction error was 19.9% for the group on the first study day and 25.6% over the entire study period (aggregate results; 6-14 days of continuous use). Two thirds of the patients exhibited no bias throughout the study period, and individual bias in the others was symmetrically distributed (three patients with underpredictions and two overpredicted). Magnitude of prediction error during the patient-controlled morphine infusions was not related to the magnitude of pharmacokinetic deviation of individual subjects from group parameters. Our results indicate that this PKPCA system provides accurate control of plasma morphine concentration when used by patients to self-administer opioid for prolonged pain relief continuously over 1 to 2 weeks.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1505613 TI - Changes in the haemodynamics of large arteries induced by single doses of nicardipine, enalapril, atenolol and urapidil. AB - Haemodynamic changes in the carotid and brachial arteries produced by single doses of four anti-hypertensive drugs (nicardipine, enalapril, atenolol, and urapidil) have been studied in 12 patients with essential hypertension. Measurements were performed noninvasively using a mechanographic method and B mode pulsed Doppler ultrasonography. Within 7 h all of the drugs had caused a significant reduction in blood pressure, whereas heart rate showed a significant change only after atenolol. All the drugs produced a marked reduction in brachial pulse-wave velocity. Only nicardipine caused a significant reduction in vessel wall tension both in the carotid and brachial arteries, while brachial peripheral resistance was significantly reduced by all the drugs except atenolol. Neither atenolol nor enalapril caused any significant reduction in carotid peripheral resistance. The results show that all four antihypertensive drugs led to a beneficial increase in arterial compliance despite their different effects on peripheral resistance. PMID- 1505614 TI - Steady state pharmacokinetic profile of indomethacin in elderly patients and young volunteers. AB - The steady-state pharmacokinetic profile of indomethacin was examined in twelve healthy volunteers (4 m, 8 f; 20-34 y) and in 12 elderly subjects (7 m, 5 f; 70 88 y). Two formulations of indomethacin were examined, providing duplicate data for each subject group. The subjects received each formulation of indomethacin (25 mg tid) for 6 days in a single blind crossover fashion. On day 7, after an overnight fast, a final 25 mg dose of indomethacin was given and plasma concentrations measured over the following 12 h. Kinetic parameters Cpmin, Tmax and AUC (0-12 h) were determined. There were no differences in the pharmacokinetic parameters between young and elderly subjects or between data for the two formulations of indomethacin. AUC values (micrograms.ml-1.h), for example, for the two formulations in the young subjects were 5.85 and 6.85 while the values for the elderly subjects were 6.55 and 6.50 respectively. When each treatment period was considered independently there was a significant difference between young and elderly subjects with regard to compliance. The rates of non compliance (over and under compliance) using a capsule count technique were, however, low with a mean maximum value of 5.8% being recorded for the elderly subjects. PMID- 1505615 TI - Paracetamol elimination in Chinese and Indians in Singapore. AB - The 24 h urinary excretion of paracetamol and its conjugates after oral administration of about 15 mg/kg was studied in 24 Chinese and 24 Indian healthy young adult male volunteers living in Singapore. The Indians excreted a significantly lower fraction of sulphate conjugate (28.9% compared to 35.9% in the Chinese), and a correspondingly higher fraction as glucuronide conjugate (62.2% compared to 54.5% in the Chinese). There was no difference between the ethnic groups in terms of the urinary recovery of unchanged paracetamol (Indians 3.4%, Chinese 3.6%), glutathione-derived cysteine (Indians 2.3% and Chinese 2.2%) and mercapturic acid (Indians 3.6%, Chinese 3.8%) conjugates. The total fraction of administered paracetamol recovered in the urine was 84.7% and 85.7% in the Indian and the Chinese groups, respectively. Although the total glutathione derived conjugates recovered in the two ethnic groups were similar (Indians 5.9%, Chinese 6%), the values were lower than those reported previously for Caucasians in Scotland (9.3%). PMID- 1505616 TI - Pharmacokinetic and blood pressure effects of carvedilol in patients with chronic renal failure. AB - The pharmacokinetic and acute systemic haemodynamic effects of a single oral dose of 50 mg carvedilol has been studied in 24 hypertensive patients with chronic renal failure. The patients were stratified into 3 groups according to the creatinine clearance: I 51-90 ml.min-1; II 26-50 ml.min-1; III 4-25 ml.min-1. The area under plasma level time curve AUC, the elimination half-life t1/2, the maximum plasma concentration Cmax, the time to peak concentration tmax were not significantly different between groups, whereas the amount of unchanged drug or metabolite excreted in urine Ae and the renal clearance CLR of carvedilol and its metabolites M2, M4, M5 were significantly decreased in Group III. Blood pressure and heart rate decreased in all 3 groups of patients after acute administration of 50 mg carvedilol. Mild adverse effects were reported in 6 patients. Despite a decrease in the renal clearance of carvedilol and of its metabolites with decreasing kidney function, its main pharmacokinetic parameters remained unchanged. The present results suggest that the dose of carvedilol need not be reduced in hypertensive patients with chronic renal failure. PMID- 1505617 TI - Population pharmacokinetics of imipramine in children. AB - The population pharmacokinetics of imipramine (IMI) and its active metabolite desipramine (DMI) have been evaluated using 177 IMI and DMI serum levels from 49 enuretic children (6-13 y) on IMI treatment. Standard two stage (STS) and maximum likelihood (ML) methods were used to estimate fixed and random effect parameters of IMI. Simultaneous estimation of the drug and metabolite parameters was carried out by the STS method. The mean value of the elimination constant of the drug and metabolite were 0.0425 h-1 and 0.0359, h-1 respectively. Significantly higher variability was found in the pharmacokinetic parameters of the metabolite. According to these estimated pharmacokinetic parameters, the recommended dose for enuretic children should be 1.7 mg.kg-1.day-1. The population pharmacokinetic parameters obtained in the study permit dosage individualisation using a bayesian algorithm. PMID- 1505619 TI - [Effect of age on the copulatory behavior of the male rat]. AB - Fifteen male SPF Wistar-Imamichi rats, aged 10, 27 and 44 weeks, that had been raised in the authors' laboratory, were used for the observation of copulatory behavior. Each male was given the opportunity to mate with a proestrous female. During a two hour period, standard measures of copulatory behavior, e.g., mounting, intromission and ejaculation, were documented by a video recording. The following results were obtained; the number of ejaculations in 10-week-old rats, over a two hour period, was 6 to 8. Males showed a subsequent post-ejaculatory interval. The males aged 27 weeks performed 3 to 4 times during the first hour, and then refrained from sexual activity. The copulatory behavior in males aged 44 weeks declined, as compared with that of their 10 and 27 weeks old counterparts. PMID- 1505618 TI - The pharmacokinetics of tiopronin and its principal metabolite (2 mercaptopropionic acid) after oral administration to healthy volunteers. AB - We have studied the pharmacokinetics of tiopronin and its principal metabolite, 2 mercaptopropionic acid (2-MPA) in healthy volunteers after the oral administration of 500 mg (2 Acadione tablets), followed by simultaneous assay of the two compounds in plasma over a period of 48 h using a new method (emission of fluorescence after HPLC and post-column derivatization by pyrene-maleimide). The absorption of tiopronin was slow (tmax between 4 and 6 h) and the plasma concentrations subsequently fell biexponentially. The principal metabolite 2-MPA appeared later in the plasma (tmax between 10 and 12 h after a lag-time of 3 h) then disappeared monoexponentially. About 15% of the tiopronin was metabolized to 2-MPA. PMID- 1505620 TI - [Age-related changes in hematological and serum biochemical values in cats]. AB - Nineteen hematological and serum biochemical values were analyzed for 91 healthy cats of both sexes (aged 1 to 48 months) that were bred and reared in our laboratory. Age-related changes were found for many parameters. Red blood cell counts (RBC), hemoglobin (Hb), hematocrit (Ht), Mean corpuscular constants, GPT, total protein (TP) and albumin (ALB) initially were low but increased then stabilized. White blood cell counts (WBC), alkaline phosphatase (ALP), inorganic phosphorus (Pi), total bilirubin (TBil), total cholesterol (TC), glucose (GLU), and triglyceride (TG) initially were high, but decreased then stabilized. No age related changes were found for GOT, blood urea nitrogen, or calcium. Of the parameters that changed with age, the mean corpuscular constants, GPT, GLU, and TG became stabilized during the first 3 to 4 months of life, but others (RBC, Hb, Ht, TP, ALB) became stabilized after 9 to 11 months, during which period body weight reached a plateau. Some parameters (WBC, ALP, TG, Pi) showed change up to 18 months of age. These results suggest that cats 9 to 11 months old can be regarded as adults; but for some parameters, cats aged 18 months, or older, are better regarded as adults. Sex-related differences in the values for mean corpuscular volume, mean corpuscular hemoglobin, and WBC that were found after 11 months of age were higher in females. ALB was higher in males. PMID- 1505621 TI - Spermatogenesis in the Watase's shrew, Crocidura watasei--a light electron microscopic study. AB - Spermatogenesis in the Watase's shrew, Crocidura watasei, was investigated by light and transmission electron microscopy. The cycle of the seminiferous epithelium was divided into 12 stages using the development of spermatids as a main criterion. The steps of spermatids were characterized by morphological changes of the nucleus and acrosomal structure. The relative frequencies of the stages 1 to x 11 were 11.0, 10.3, 6.8, 10.6, 24.0, 6.4, 4.4, 7.9, 6.4, 4.9, 3.7 and 3.6%, respectively. Four types of spermatogonia (A1, A2, In and B) could be discerned by the observation of whole mount samples. The development of spermatids was divided into four phases (Golgi, cap, acrosome and maturation phases), as in other mammals. In Golgi phase of the spermatid, several acrosomal granules were encountered. In cap phase, the acrosome gradually spread over the nuclear surface. In early acrosome phase, the acrosome began to elongate and reached the maximal length in step 8 spermatids. The acrosome of step 8 spermatids was twice as long as that of spermatozoa. In late acrosome phase, the acrosome was on the way of shrinkage. Finally, the fan-shaped acrosome was formed in maturation phase. These findings suggested that the process of acrosomal formation was quite characteristic in the Watase's shrew in that the spermatid acrosome elongated most prominently in the mammals hitherto examined. PMID- 1505622 TI - Hematological and clinico-biochemical characteristics of leukemia in Fischer 344 rats. AB - Seventy-one male and 52 female F 344 rats with leukemia used as controls in the 30-month inhalation studies were characterized by hematological and clinico biochemical findings. Hematological findings revealed that the leukocyte count, mean corpuscular volume, and mean corpuscular hemoglobin increased in both sexes of leukemic rats showing profound anemia, while the platelet count, erythrocyte count, hematocrit, and hemoglobin concentration decreased. In these rats, the serum levels of low density lipoprotein, free cholesterol, total bilirubin, blood urea nitrogen, and triglyceride and the activities of glutamic oxalacetic transaminase, glutamic pyruvic transaminase, creatine phosphokinase, alkaline phosphatase, and lactate dehydrogenase increased markedly and the level of high density lipoprotein, the oxygen partial pressure, and the cholinesterase activity decreased. Clinical signs such as decrease in redness of the eyes, decrease in body weight, abdominal distension, staining of the public region, and debility were seen in most leukemic animals. These clinical signs and hematological and clinico-biochemical findings may be helpful in diagnosis of leukemia in long-term experiments. PMID- 1505623 TI - H-2 haplotype and sex-related differences in IgG response to ovalbumin in mice. AB - Specific IgG antibodies were determined by enzyme-linked immunosorbent assay (ELISA) in 7 strains of male and female mice after immunization with ovalbumin. Also, H-2 haplotype and sex-related differences in IgG response to ovalbumin were evaluated using statistical methods, slope ratio assay and parallel line assay. H 2k strain mice (C3H/HeN and CBA/JN) showed higher IgG responsiveness to ovalbumin than H-2d (BALB/cAnN and DBA/2 N) and H-2b (C57BL/6 N) mice. With regard to the sex-related differences in IgG response to ovalbumin, females in some strains showed higher IgG response than males, but some strains showed no sex-related differences, and sex-related differences in IgG response to ovalbumin did not relate to their H-2 haplotypes. These results may be caused by other immune response genes which control the sex-related immune response than H-2 or other unknown factors. PMID- 1505624 TI - [Hematological and serum biochemical changes with age in term fetuses, offspring and dams in normal Sprague-Dawley rats]. AB - Hematological and serum biochemical values of dams and offspring of Sprague Dawley rats were measured during late gestation, lactation and postweaning. In dams, slightly low erythrocytic parameters, high platelets and high frequency of neutrophils were seen after parturition although WBC showed no marked changes. On Day 20 of gestation, glucose and triglycerides were extremely high and TP and albumin were low. These changes may be attributed to pregnancy or parturition. In fetuses on Day 20 of gestation and offspring immediately after birth, erythrocytes showed anisocytosis, polychromasia, basophilic stipplings and Howell Jolly bodies and erythroblasts were found. RBC was low. MCV and MCH were extremely high, compared to adult erythrocyte levels. Hemoglobin and hematocrit slightly decreased before weaning. RBC, hemoglobin and hematocrit increased with age and reached adult levels by Day 56. MCV and MCH values decreased, towards adult levels, until weaning. Platelets rapidly increased and reached adult levels before weaning. WBC increased after birth having higher counts in males than in females on Day 35 and thereafter. Glucose, TP and albumin increased with age and reached adult levels by Day 28. ALP was high in fetuses and changed with age having two peaks similar to those reported in man. Cholesterols gradually increased after birth and had a peak on Day 14. Urea nitrogen, inorganic phosphorus and calcium were slightly high in fetuses and preweaned offspring. Potassium was high in fetuses but no age-related trends were seen in offspring. PMID- 1505625 TI - Naturally occurring Mycobacterium scrofulaceum infection in a laboratory mouse colony. AB - A contamination with Mycobacterium scrofulaceum was experienced in a colony of BALB/c-nu/nu mice. The contamination was noticed after introduction of C57BL/6 and C57BL/6. Lyt l. 1 strains into facilities that kept the colony. M. scrofulaceum seemed to be spread by oral infestation and cross-contamination of fecal excretions during handling of the mice. The organisms were shed continually or intermittently into feces of weaned nu/+ and nu/nu mice of BALB/c background, and were isolated from the mesenteric lymph nodes and spleen of some of the mice. Some of the bacillus-carrying mice developed serum antibody to M. scrofulaceum of IgG and IgA classes and gave a low degree of hypersensitivity to PPD from M. tuberculosis. PMID- 1505626 TI - Studies on teratological testing using chicken embryos--effects of solvents, injection sites and the age of the embryo. AB - The purpose of this study was to examine the effects of solvents, injection sites and embryo age when using chicken embryos for teratological testing. The results obtained were as follows: 1) Solvents: distilled water, physiological saline, sesame oil, 25% ethanol, 0.5% carboxymethylcellulose and 0.1% methylcellulose solution were not toxic in Day-4 embryos (eggs incubated for 4 days). 2) With 6 aminonicotinamide, air space injection more effectively induced malformations in chicken embryos. With boric acid, however, yolk sac injection was better. It was shown therefore that the appropriate injection site varied according to the test drug. 3) 6-aminonicotinamide induced characteristic malformations when injected into embryos of various ages ranging from 4 to 13 days of incubation. On the other hand, boric acid was teratogenetic only when injected into Day-3 or Day-4 embryos. It seems, therefore, that the age of the embryo at the time of administration is of critical importance and that the optimum time of administration varies according to the test drug. PMID- 1505627 TI - [Evaluation of enzyme-linked immunosorbent assay for serodiagnosis of Bordetella bronchiseptica infection in guinea pigs]. AB - An enzyme-linked immunosorbent assay (ELISA) for serodiagnosis of Bordetella bronchiseptica (B. bronchiseptica) infection in guinea pigs was evaluated. An isolate of B. bronchiseptica from lung lesion of a guinea pig was used as antigen after ultrasonication. In the experimental infection, specific pathogen-free guinea pigs inoculated with the bacterium intranasally were examined every 5 or 10 days. The organism was recovered from all animals between 5 and 30 days post inoculation (p.i.). Only one animal was sero-positive by agglutination test 30 and 50 days p.i.; whereas, by ELISA, one animal was positive 5 days p.i., and all the animals showed strong reaction 20 to 50 (end of experiment) days p.i. Field samples obtained from 1983 to 1989 were tested by ELISA. The results corresponded to those of macroscopic observations and bacterial isolation. The ELISA proved to be useful method for detection of B. bronchiseptica infection in guinea pigs. PMID- 1505628 TI - Usefulness of ophthalmic examination in postnatal observation in teratology studies. AB - Pregnant rats were irradiated with soft x-ray at a dose of 635 r or 1270 r on Day 9 or 11 of gestation. The eyes of F1 offspring were examined by indirect ophthalmoscopy and slit lamp biomicroscopy in postnatal weeks 3 to 7. Ophthalmoscopic examination of offspring irradiated at a dose of 635r or 1270r on Gestational Day 9 revealed iris and choroidal coloboma together with microphthalmia and anophthalmia at Postnatal Week 3 or later. Choroidal coloboma, an anomaly that cannot be detected by the common external observation method, was found ophthalmoscopically in one rat without any external ocular abnormalities. This fact suggests that ophthalmoscopy in postnatal observation can be useful to detect ocular teratogenic potential of test compounds in preclinical safety studies. PMID- 1505629 TI - Congenital diverticulum of the ileum in a rat. AB - A congenital diverticulum of the ileum (Meckel's diverticulum), approximately 10 mm long, was detected in a rat and examined histologically. The histological findings were basically the same as in the ileum. Although Meckel's diverticulum is uncommon in the rat, the present report demonstrated the possibility of discovering new cases. PMID- 1505630 TI - [Apparatuses for obtaining continuous 24-hour records of water intake and urinary output in dogs]. AB - Two apparatuses were constructed to obtain continuous records of water intake and urinary output in a dog. As a validation of their accuracy, daily patterns of these measurements were observed on a beagle using these two apparatuses during non-treatment and treatment of the diuretic drug, flosemide. During the non treatment, water intakes increased after feeding, but urinary outputs did not show a regular pattern. These patterns were the same as the previously reported patterns. During the treatment, urinary output increased within one hour after treatment. These results show these apparatuses are useful in measuring water intake and urinary output continually on the experimental dog. PMID- 1505631 TI - Histological observation on the female prostate in Mongolian gerbils (Meriones unguiculatus). AB - In Mongolian gerbils, prostatic buds were found in female fetuses at the 23rd day of gestation. In the mothers the well-developed prostate gland consisting of a paired lobes was situated on either side of the neck of the bladder. PMID- 1505632 TI - [Embryo transfer through the wall of the fallopian tube in mice]. AB - Two-cell mouse embryos obtained by in vitro fertilization were transferred into the ampulla of the fallopian tubes of pseudopregnant recipients through the wall of the tubes on day 1 of pseudopregnancy. A total of 112 embryos were transferred to 7 pseudopregnant recipients and 68 young (60.7%) were born. PMID- 1505633 TI - [Occlusion-reperfusion model of cerebral ischemia in Fischer 344 rats]. AB - The effect of transient cerebral ischemia (from 15 to 180 min) by bilateral carotid arterial occlusion on postischemic mortality rate and the signs of nervous disorder in Fischer 344 rat was studied. Total mortality rate was 40 to 60% during 72 hr of reperfusion following 2 hr ischemia. Postischemic mortality rate did not vary distinctly with 10, 20 and 40 weeks-old. PMID- 1505634 TI - [A 1990 report on the actual state of the care and management of experimental animals in Japan. JALAS Subcommittee on Standards Relating to the Care and Management, etc. of Experimental Animals]. PMID- 1505635 TI - CSF-1 deficiency in the op/op mouse has differential effects on macrophage populations and differentiation stages. AB - Osteopetrosis and the absence of colony-stimulating factor 1 (CSF-1) in op/op mice are associated with decreased cellularity of the bone marrow (to one tenth of the normal), a very significant reduction in the number of cells recovered from peritoneal, pleural, and alveolar lavages, moderate leukopenia, and a slight decrease in the number of cells per spleen and thymus. Furthermore, op/op mice possess deficiencies in the number of macrophages in various organs. These cells are apparently absent in the bone marrow, severely reduced (5%-15% of the normal number) in peritoneal and pleural cavities and in the lungs. In addition, a marked decrease in the frequency and total number of circulating monocytes is present (5% of the normal). The deficiency of macrophages is less severe in the liver, spleen, and thymus of op/op mice (approximately 30% of those seen in normal). There is a concomitant redistribution of macrophage progenitor cells (granulocyte-macrophage colony-forming units, CFU-GM) in op/op mice from the marrow to the spleen and liver, associated with an increased sensitivity to interleukin 3 (IL-3). Their total number is decreased at least threefold compared to control mice. Moreover, op/op mice have at least a fivefold reduction in the total number of day-11 spleen colony-forming units (CFU-S) associated with their redistribution to the spleen and liver. These data suggest that the macrophage system in op/op mice is reduced at all levels tested, that is, at the level of mature macrophages, the level of progenitors, and the level of stem cells, whereas the redistribution of progenitor and stem cells could be viewed as a secondary consequence of osteopetrosis. Furthermore, these data suggest that macrophage dependency in vivo on CSF-1 is limited and different in various organs. Particularly in the liver, spleen, and thymus, other growth factors may significantly compensate for CSF-1 deficiency. Based on the relative decrease in the number of CFU-GM in the op/op mice, it appears that the population size of these progenitors is less dependent on CSF-1 than the hematopoietic stem cell population size as evidenced by the day-11 CFU-S assay. The day-11 CFU-S population is severely reduced in op/op mice, suggesting a physiological involvement of CSF-1 in expanding its size. These data provide evidence that CSF 1, besides acting on the final and intermediate stages of macrophage maturation, may also play a role in early stages of hematopoiesis. PMID- 1505636 TI - Abnormal CD4:CD8 ratios and delayed germinal center reconstitution in lymph nodes of human graft recipients with graft-versus-host disease (GVHD): an immunohistological study. AB - We searched for evidence that immunodeficiency in graft-versus-host disease (GVHD) is in part due to alloimmune damage to lymph nodes. We used immunoperoxidase techniques to stain T-cell subsets, pan-B cells, and follicular dendritic reticular cells (FDRC) in frozen sections of lymph nodes from 80 marrow graft recipients (56 with GVHD, 11 autografts, and 13 allografts without GVHD). We found that 46% of the GVHD patients had reversed CD4:CD8 ratios and only 13% of non-GVHD patients had such disturbed ratios (p = 0.006). Pan-B (CD22) cell labeling was present in the follicular regions of 73% of patients without GVHD and only 53% of patients with GVHD (p = 0.05). Focal FDRC staining was geographically concordant with clusters of B cells in 88% of cases (p less than 10(-7)). These data confirm that disturbed intranodal CD4:CD8 ratios are present more frequently in GVHD patients than in non-GVHD patients or in autografted patients. They suggest more delayed follicular B-cell reconstitution in GVHD patients. They show an extremely tight association of FDRC with clusters of B cells in the recovering lymph node, as in the developing fetal node. We hypothesize that the lack of follicular dendritic cells may contribute to dysfunctional B-cell maturation by ablating orderly antigen presentation and clonal expansion in the lymph node cortex. PMID- 1505637 TI - Polyethylene glycol (PEG)-modified granulocyte-macrophage colony-stimulating factor (GM-CSF) with conserved biological activity. AB - Polyethylene glycol (PEG) modification improves the pharmacological properties of proteins, usually extending plasma half-life and concomitantly increasing in vivo bioactivity, reducing both antigenicity and immunogenicity, and increasing solubility and resistance to proteolysis. Despite these established benefits, few PEG proteins are in use. Current coupling methods are either traumatic for the protein or involve lengthy and difficult procedures to activate monomethoxyPEG (MPEG). We have applied a new coupling method that allows coupling of MPEG directly to proteins under physiological conditions. Using this method with recombinant human (rh)granulocyte-macrophage colony-stimulating factor (GM-CSF) we were able to construct biologically active PEG-GM-CSF. Fast protein liquid chromatography (FPLC) and phase-partitioning confirmed the presence of PEG modification, and the former was used to fractionate modified and unmodified material. Bioactivity was measured in colony assays of normal human bone marrow cells and by tritiated thymidine uptake (of chronic myeloid leukemia cells and TF 1 cells). With both uptake and colony assays, using unfractionated material, we observed only a modest reduction in biological activity. Assays of FPLC fractionated material confirmed that much of the bioactivity of the PEG-GM-CSF preparations was due to the modified species and any residual unmodified GM-CSF. Species uncontaminated by tresylmonomethoxyPEG (TMPEG; which was somewhat inhibitory in the thymidine uptake assay and eluted over a broad region of the FPLC profile) had no significant reduction in activity, but we cannot rule out the possibility that PEG-GM-CSF species eluting elsewhere in the profile had modest reduction of activity. Subcutaneous injection into mice confirmed the anticipated improved half-life in vivo and demonstrated a longer uptake from the injection site. This is, as far as we are aware, the first successful construction of PEG-GM-CSF with conserved biological activity. PMID- 1505638 TI - Puritans. PMID- 1505639 TI - Transforming growth factor beta 1 systemically modulates granuloid, erythroid, lymphoid, and thrombocytic cells in mice. AB - Transforming growth factor beta 1 (TGF-beta 1) has been shown to inhibit the development of most early hemopoietic progenitors in vitro. The present series of in vivo experiments show that TGF-beta 1 can simultaneously augment and suppress distinct cell lineages in peripheral and central hemopoietic compartments. Mice treated daily for 7-14 days with s.c. injections of TGF-beta 1 exhibited up to a 95% reduction in circulating platelets and a 50% reduction in red cell counts, whereas a 50%-400% increase occurred in circulating white cells with the morphology of small lymphocytes. Decreased erythrocytes were also evident in the splenic red pulp and bone marrow sinusoids. A dramatic increase in granulopoiesis occurred in the spleen and bone marrow, followed by a peripheral neutrophilia 1 week after treatments ceased. All effects were completely reversible, with normal histologic and hematologic profiles evident 2 weeks after cessation of treatments. Thus, TGF-beta 1 can differentially regulate multiple hemopoietic pathways in a systemic, reversible, and dose-dependent fashion. These actions may be mediated by the direct effects of TGF-beta 1 or through modulation of secondary cytokines and receptors. PMID- 1505640 TI - Alterations in erythropoiesis in TGF-beta 1-treated mice. AB - Chronic treatment of mice with transforming growth factor beta 1 (TGF-beta 1) resulted in a dose-dependent inhibition of erythropoiesis. Following 14 daily s.c. injections of 5 or 25 micrograms of TGF-beta 1, a significant degree of anemia was observed. In addition, erythroid progenitor cells were present in reduced numbers in the bone marrow and spleen. Pluripotent stem cells were present in normal numbers in the bone marrow of mice treated with 25 micrograms of TGF-beta 1. However, significantly elevated levels were present in the peripheral blood. Adequate levels of erythropoietin were present in TGF-beta 1 treated mice. Following suspension of treatment with TGF-beta 1, erythropoiesis was restored, and TGF-beta-treated mice were able to compensate the anemia. One week following treatment, only mice treated with 25 micrograms of TGF-beta 1 continued to show evidence of anemia. However, in contrast to 1 day following treatment, these mice had levels of reticulocytes that were significantly above control values. In addition, erythroid progenitor cells had returned to normal levels in the bone marrow and were present in elevated levels in the spleen in both groups of TGF-beta 1 treated mice. The results provide evidence that the anemia associated with sustained TGF-beta 1 treatment is the result, in part, of a reversible inhibition of the maturation of erythroid progenitor cells. PMID- 1505641 TI - Origin of stromal cells associated with osteoclast recruitment in s.c. implants of bone particles in chimeric mice. AB - Subcutaneous implantation of devitalized bone particles (BPs) in mice elicits a fibrovascular response with subsequent differentiation of multinucleated osteoclast-like cells. In bone marrow, stromal cells are known to play important roles in controlling hematopoiesis. Similarly, the stromal cells in the initial reaction to BPs may take part in supporting subsequent osteoclast recruitment and differentiation within the implants. Cross-gender chimeric mice were used to allow determination of whether these stromal cells were derived from local tissue or from hematopoietic stem cells. In radiation-chimeric mice, there was a 7-day delay in stromal recruitment and osteoclastic differentiation. Therefore cultures were established from the stromal tissue elicited 11 days after implantation, prior to osteoclastogenesis. Analysis of Y-chromatin DNA from these lines demonstrated that the majority (97%) of the lines were of recipient origin. It is possible that these fibroblast-like cells migrate to the site of BP implantation and play a role in the initiation of osteoclast development. This model can be used to define cellular interactions in osteoclastogenesis. PMID- 1505642 TI - Protection of cells capable of reconstituting long-term bone marrow stromal cultures from 4-hydroperoxycyclophosphamide by interleukin 1 and tumor necrosis factor. AB - The cytokines interleukin 1 (IL-1) and tumor necrosis factor-alpha (TNF-alpha) have been implicated in protecting normal hematopoiesis from both irradiation and chemotherapy damage. The mechanism of action of these cytokines and which cells are protected is not known. In this study, we report on the ability of IL-1 and TNF-alpha to protect hematopoietic cells capable of repopulating irradiated long term bone marrow stromal cultures from 4-hydroperoxycyclophosphamide (4-HC). Irradiated long-term bone marrow cultures recharged with hematopoietic cells pretreated with IL-1 and TNF-alpha prior to 4-HC were shown to give rise to greater numbers of colony-forming cells at 4-5 weeks of culture within both the nonadherent and adherent cell populations of the long-term cultures when compared to controls. These results suggest that IL-1 and TNF-alpha can protect human long term culture-initiating cells, which are closely related to reconstituting stem cells. PMID- 1505643 TI - Induction of human monocyte cell line U937 differentiation and CSF-1 production by phorbol ester. AB - The monoblast-like human histiocytic lymphoma cell line U937 can be induced by phorbol 12-myristate 13-acetate (PMA) at concentrations of 8-16 ng/ml to undergo differentiation. The induced cells show growth inhibition, morphological changes to monocyte-macrophage-like cells, and increases in nitroblue tetrazolium (NBT) and nonspecific esterase activities. The expression of surface markers MO1 and MO2 for macrophages is also elevated. The induced differentiation of U937 cells is accompanied by the appearance of colony-stimulating activity in the culture medium as assayed on mouse bone marrow cells. Gel filtration chromatography of the conditioned media shows a peak of colony-stimulating factor (CSF) activity with an apparent molecular weight of approximately 100 kd. Morphological analysis of the colonies reveals a predominant monocyte-macrophage population. This CSF activity can be neutralized by anti-human colony-stimulating factor 1 (CSF-1) antibody, and Western blot analysis shows a CSF-1 band. All these results strongly indicate that CSF produced by induced U937 cells is CSF-1. Northern blot analysis of RNA isolated from U937 cells demonstrated that CSF-1 gene expression started after PMA induction for 3 h and declined after 18 h. Protooncogenes c-fos and c-jun were expressed after half an hour of incubation with PMA. PMID- 1505644 TI - A method for rapid analysis of peripheral blood mononuclear leukocyte cytokine mRNA. AB - Interleukins, hematopoietic growth factors, and adhesion molecules mediate multiple components of the inflammatory response. Conventional methods for purification of cytokine-producing cells are time consuming and can, therefore, depending on the conditions of cell purification and the nature of the mRNA being purified, result in both over- and underestimates of mRNA content. Therefore, it has been difficult to quantify such factors in ways that are unambiguously reflective of in vivo cytokine production. We describe herein a method for such rapid preparation of peripheral blood mononuclear leukocytes (PBML) that amounts of cytokine mRNA derived from these cells, apart from readily quantifiable losses during RNA preparation, will be reflective of quantities in vivo. Small quantities (10(5) of normal PBML were isolated by density centrifugation of heparinized blood for 1.25 min in a capillary tube. Poly(A)+ RNA isolated by oligo(dT)-cellulose column chromatography was sufficient to reverse transcribe both antigen-specific T-cell-receptor beta-chain mRNA and interleukin 6 (IL-6) mRNA and subsequently amplify the cDNA with Taq polymerase in reverse transcription-polymerase chain reactions (RT-PCR). Although IL-6 mRNA was not present in normal PBML, PBML incubated in culture medium for only 3 h contained approximately one molecule per cell. Because of its rapidity this technique will permit quantification of cytokine mRNA in the steady state and in clinical setting of inflammation. Because the method requires only a small quantity of blood it can be applied to clinical research studies involving children. PMID- 1505645 TI - Phenotypic heterogeneity associated with defective apolipoprotein B-100 and occurrence of the familial hypercholesterolemia phenotype in the absence of an LDL-receptor defect within a Canadian kindred. AB - Of 163 individuals with a diagnosis of heterozygous familial hypercholesterolemia (FH), only one subject was found to be positive for familial defective apo B-100 (FDB). The eight-member kindred ascertained through this subject who presented with both a clinical phenotype of FH and the FDB apo B-100 (Arg3500----Gln) mutation was studied. Plasma lipid and lipoprotein profiles, apo E phenotypes, apo B gene markers at the 3' hypervariable region and LDL-receptor haplotypes (ApaLI, PvuII, NcoI), were determined, together with LDL-receptor activity on freshly isolated blood lymphocytes. The FDB mutation, present in four relatives, was associated with three different phenotypes: FH and severe hypercholesterolemia, moderate hypercholesterolemia and normolipidemia. The FH phenotype occurred in the absence of any functional LDL-receptor defect. In homozygotes for the absence of the PvuII cutting site who had the apo B mutation, LDL-cholesterol levels were low in the presence of the apo E3/2 phenotype and high in the presence of the apo E4/4 phenotype. None of the major known environmental influences accounted for the wide range of variation in LDL cholesterol among the affected members. Further observations in the spouse and offspring of the normolipidemic FDB subject confirmed the association of apo E4, the FDB mutation and the PvuII(-/-) genotype with high cholesterol levels. It is concluded that the phenotypic expression of the FDB mutation may vary widely as a function of the genetic environment within a family.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1505646 TI - Focus on anti-atherosclerotic therapy. AB - Calcium antagonists (CA) exert an anti-atherosclerotic effect in cholesterol-fed rabbits through reduction of cholesterol accumulation in the arterial wall. Further studies in our Institute indicate that verapamil-like compounds and diltiazem stimulate receptor-mediated LDL uptake by human fibroblasts in culture, while nifedipine-like compounds and flunarizine are inactive. Verapamil and diltiazem stimulated LDL-receptor activity also in cells from a heterozygous FH patient, while they were inactive in a receptor defective homozygous FH patient. A basic group needs to be present on the CA molecule to modulate the LDL receptor expression. Preliminary data in our laboratory suggest that some CA can achieve concentrations in the aortic wall likely to exert effects on LDL receptors. This stimulatory activity may improve lipid metabolism in the arterial wall. PMID- 1505648 TI - Activity profile of gemfibrozil on the major plasma lipoprotein parameters. AB - Gemfibrozil (G) is a widely used and highly effective fibric acid derivative. It acts both on lipoprotein disorders characterized by hypertriglyceridemia, as well as in hyperchlolesterolemia. The results of two separate studies are summarized, in order to elucidate the differential activity profile of the drug on the major plasma lipoprotein parameters. In a group of hypertriglyceridemic patients (Study I) the major activity of G was on the VLDL cholesterol (C) and triglyceride levels (respectively -40.4 and -35.7%), associated with a marked increase of the HDL-C levels, in particular in the HDL3 subfraction. In addition, apolipoprotein B levels were significantly reduced (-12%) in all treated patients. In Study II, treatment with G in severe hypercholesterolemia was compared to that with pravastatin, a major hydroxymethylglutaryl coenzyme A reductase inhibitor. G, in these patients, markedly reduced both total (-21.6%) and LDL-cholesterol (-24.4%) levels. The increase of HDL-C was less marked than in type IV patients but G, similarly to pravastatin, induced a significant reduction of apolipoprotein B, together with an increase (+19.2%) of apolipoprotein AII levels. These findings indicate that the activity profile of G is wider than expected and that it may include a reduction of LDL levels in severely hypercholesterolemic patients. The mechanism of this latter change is difficult to establish, although it may also be related to an improved delipidation of LDL, resulting in a more efficient interaction with peripheral high affinity receptors. PMID- 1505647 TI - Concept of an antiatherosclerotic efficacy of calcium entry blockers. INTACT Investigators. AB - Animal experiments suggest an inhibitory effect of calcium entry blockers on arterial calcinosis and the formation of atherosclerotic plaques. Experiments with isolated tissues suggest various mechanisms for an antiatherosclerotic effect of calcium entry blockers. INTACT, the International Nifedipine Trial on Antiatherosclerotic Therapy, is the first study investigating, with a prospective, placebo-controlled, randomized, double-blind design, the influence of a calcium entry blocker (nifedipine 80 mg/day) on the progression of coronary atherosclerosis in patients with proven coronary artery disease. Study endpoints were changes of established coronary stenoses (diameter reduction greater than or equal to 20%), as well as the formation of new stenoses as documented by coronary angiography. Standardized coronary angiograms were taken before and after a treatment period of 3 years. The angiograms were quantitatively analyzed with the computer-assisted edge detection system CAAS. Of the 425 patients included in the study, 282 patients (134 on nifedipine and 148 on placebo) revealed no protocol violations. In the inclusion angiograms of these patients, 893 coronary stenoses were detected which were not significantly influenced in their development by nifedipine. However, 196 entirely new coronary lesions, 185 stenoses and 11 occlusions, were found in the follow-up angiograms. There were 78 lesions in 54 patients (40%) on nifedipine (0.58 new lesions/patient) and 118 lesions in 73 patients (49%; n.s.) on placebo (0.8 new lesions/patient; p = 0.031). In two other studies on the inhibiting effect of dihydropyridine calcium entry blockers on the progression of coronary artery disease in man defining angiographic endpoints, the drugs were also shown to reduce the number of newly formed significant coronary lesions. If further trials in man confirm a protective role of calcium entry blockers against the formation of atherosclerotic coronary lesions, a new strategy in the prevention of coronary artery disease has to be considered. PMID- 1505650 TI - Insulin and atherogenesis. AB - A number of processes are involved in the pathogenesis of atherosclerosis. These include an "injury" to the endothelial cell barrier of the inner lining of the artery, infiltration of the artery by lipid filled monocyte-macrophages, proliferation of smooth muscle cells, synthesis of connective tissue and thrombus formation. Insulin may be involved in several of these processes. Over 40 years ago it was shown that insulin is necessary for the production of experimental atherosclerosis in cholesterol fed, alloxan diabetic rabbits. Insulin inhibits regression and stimulates formation of lipid containing lesions in a number of species, and can promote lesions in animals fed normal diets. Insulin is also related to lipid metabolism in the artery wall and interacts with blood pressure to stimulate lipid synthesis in arteries. Arterial smooth muscle cells cultured from a number of species including humans proliferate in response to levels of insulin similar to those found in normal human physiology. The proliferative effects of insulin are mediated by the insulin-like growth factor receptor and hence may not be impaired in states of insulin resistance. Insulin also stimulates arterial smooth muscle cell migration. Insulin stimulates cholesterol synthesis in cultured smooth muscle cells and enhances LDL receptor activity in a number of cell types. Insulin stimulates connective tissue synthesis, and promotes clotting. PMID- 1505649 TI - Atherogenic profiles in insulin-dependent diabetic patients and their treatment. AB - Longitudinal studies have shown a large excess of cardiovascular mortality in insulin-dependent diabetic patients (IDDM) as compared to non-diabetic controls. Although diabetes appears to be an independent cardiovascular risk factor, increases in total and LDL-cholesterol together with a decrease of HDL cholesterol are more pronounced in diabetics with cardiovascular disease. The general opinion, however, derived from a large number of cross-sectional studies, is that in well-controlled IDDM lipoprotein abnormalities are modest and only slightly different from matched non-diabetic controls. Most of the studies, however, used absolute criteria based on consensus statements and do not take the internal relations of the lipoproteins into account. When atherogenic indices (such as the relationship between total cholesterol and HDL-cholesterol or the Apo A1/apo B quotient) are used, 20 to 30% of an IDDM population considered to be in clinically acceptable control have to be considered pathological. This observation is even more important since the recent Diabetes Control and Complications Trial has shown that, especially in the younger group of patients, significantly higher total cholesterol and triglycerides and lower HDL cholesterol were observed. Especially in these patients can diet and drug intervention be the most useful in the prevention of cardiovascular disease. These data are consistent with the fact that more sophisticated techniques have previously shown atherogenic changes in the composition of the VLDL-particles and lipoprotein enrichment in apo B. Since these techniques are not easily available in the clinic one has to refer to more classical techniques and the use of above mentioned atherogenic profiles to decide treatment. PMID- 1505651 TI - Insulin resistance--modelling studies. AB - Elevated insulin concentrations are independent predictors of coronary heart disease (CHD) and are related to high blood pressure, low serum HDL-cholesterol and elevated serum triglyceride. Insulin resistance is a major determinant of the plasma insulin concentration. Computer modelling of plasma glucose, insulin and C peptide concentrations during an intravenous glucose tolerance test enables quantification of the determinants of plasma insulin concentration. The association between risk markers of CHD and model-derived measures of determinants of plasma insulin concentration in a group of healthy males has been investigated. In univariate linear regression analysis of the glucose, insulin and C-peptide data, the incremental insulin area during the second phase (10-180 min.) was found to be the strongest predictor of lipid, lipoprotein and blood pressure variables. Variations in insulin sensitivity and hepatic insulin throughput contribute to variation in the insulin response and may be secondary correlates of lipids, lipoproteins and blood pressure. PMID- 1505652 TI - Characterization of a family with moderate hypercholesterolemia and binding defective low density lipoprotein. AB - Familial defective apolipoprotein B-100 (FDB) is a genetic disorder presenting with hypercholesterolemia and abnormal low density lipoprotein (LDL) that binds poorly to LDL receptors. This disease appears to be caused by a mutation in the apo B gene. In the present study thirteen members of a family with moderate hypercholesterolemia (250-350 mg/dl) were investigated. Biochemical studies on cultured skin fibroblasts ruled out classical familial hypercholesterolemia (receptor deficiency). LDL from nine affected members displayed, in an "in vitro" cell binding assay, a reduced affinity (2.5 fold) for the receptor, and had normal electrophoretic mobility, size and chemical composition. Lp(a) levels in family members were comparable to those present in normolipidemics and lower than those observed in primary hypercholesterolemia. The disorder is transmitted over three generations as an autosomal codominant trait and all the affected members are heterozygotes and hypercholesterolemic. PMID- 1505653 TI - Serum lipoprotein profile in the Mediterranean variant of glucose-6-phosphate dehydrogenase deficiency. AB - Sardinian males with erythrocyte glucose-6-phosphate dehydrogenase (G-6-PD) deficiency have lower serum levels of total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C) and apolipoprotein B (ApoB), compared to normals. Since the enzyme deficiency is expressed also in nucleated cells, we studied cholesterol (C) and DNA synthesis and LDL-receptor expression in freshly isolated circulating mononuclear cells from normal and G-6-PD-deficient Sardinians. Synthesis of C (as 14C-acetate incorporation) and of DNA (as 3H-thymidine incorporation) was clearly reduced, both in basal state and after PHA stimulation, in G-6-PD-deficient cells compared to normal cells. On the other hand, no clear influence of G-6-PD deficiency on LDL-receptor expression could be demonstrated. The Mediterranean variant of G-6-PD deficiency is characterized, whatever the metabolic mechanism may be, by a serum lipoprotein pattern of reduced atherogenicity. PMID- 1505654 TI - Association of a polymorphism in the Apo AI gene promoter with hyperalphalipoproteinemia. AB - The distribution of a polymorphism due to an Adenine to Guanine transition in the ApoAI gene has been studied in 136 women and 108 men, through amplification of the promoter region of the gene and allele-specific oligonucleotide hybridization. The allelic frequencies for the A allele were 0.10, 0.14 and 0.27 in women and 0.08, 0.17 and 0.14 in men for the lowest decile, intermediate group and the highest decile of HDL-cholesterol levels, respectively. Statistical analysis showed that the A allele was associated with high HDL-cholesterol levels in women, but not in men. PMID- 1505655 TI - The molecular defects in lipoprotein lipase deficient patients. AB - The underlying molecular defects that lead to a deficiency of lipoprotein lipase in two patients from different kindreds presenting with the familial hyperchylomicronemia syndrome have been identified. Sequence analysis of amplified LPL cDNA of the patient from the Bethesda kindred revealed a single point mutation (G to A) at position 781 of the normal gene that resulted in the substitution of an alanine for a threonine at residue 176 and the loss of an SfaN1 site present in the normal LPL gene. Amplification of patient cDNA by the PCR followed by restriction enzyme digestion with SfaN1 established that the patient is a true homozygote for the defect. The proband from the second kindred was found to be a compound heterozygote for two separate allelic mutations, including a T to C transition at nucleotide 836 and a G to A mutation at base 983 that led to the substitution of Ile194 by Thr and Arg243 by His, respectively. Transient expression of the mutant LPL cDNAs from both kindreds in human embryonal kidney-293 cells resulted in the synthesis of enzymatically inactive proteins, establishing the functional significance of the mutations. PMID- 1505656 TI - Factor VIII and coronary heart disease. AB - In plasma, Factor VIII is bound to its carrier protein, von Willebrand Factor (vWF). Therefore, the levels of these two factors vary together. From studies in the general population, in patients with coronary heart disease and in hemophilia patients, an association between Factor VIII levels and coronary heart disease clearly emerges. PMID- 1505657 TI - Plasma fibrinogen and factor VII as risk factors for cardiovascular disease. AB - The importance of the thrombotic component of coronary heart disease is increasingly recognised, and in particular the role of the coagulation system in this process. The Northwick Park Heart study was the first major prospective study to identify both fibrinogen and factor VIIc as risk factors, as powerful as total cholesterol in predicting ischaemic events. Since then, a number of epidemiological studies have confirmed the importance of fibrinogen, not just in CHD but in stroke as well. A variety of environmental factors are known to influence levels of factor VII and fibrinogen and therefore support their role in the development of coronary thrombosis. Both are known to increase with age and body weight and are relatively elevated in diabetes. Fibrinogen is strongly related to smoking habit and a substantial proportion of the IHD risk associated with smoking is mediated through this relationship. There is a dose response effect between number of cigarettes smoked and level of fibrinogen and an inverse relationship with time since cessation of the habit. Factor VII is known to correlate with total cholesterol level, and there is a relationship between dietary variability of fat intake and factor VII, which is likely to play an important role in the risk of CHD. The case for using either anticoagulation or anti platelet agents in secondary prevention of myocardial infarction is now clear, but there are still uncertainties in primary prevention which relate to the ideal dose intensity of either aspirin or anti-coagulation and the type of patient most likely to benefit. The ongoing Thrombosis Prevention Trial identifies middle-aged males at high risk of a myocardial infarction.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1505658 TI - Fibrinogen and mechanisms of thrombosis. A difficult link. AB - Epidemiological observations indicate that high plasma fibrinogen levels are strongly correlated to the frequency of two major thrombotic complications of atherosclerosis: stroke and myocardial infarction. Thrombosis is increasingly recognized as a central mechanism in stroke and myocardial infarction, and fibrinogen is involved in events thought to play a major role in thrombosis. Therefore, elucidation of the relationship between fibrinogen and thrombosis may strengthen the predictive value of this protein and define new interventions against stroke and myocardial infarction. In addition, advances in the understanding of the atherogenic potential of several risk factors of coronary heart disease took advantage of information emerging from the measurement of the factor in population-based studies. Thus, it is conceivable that measuring plasma fibrinogen to predict stroke and myocardial infarction is a major direction to be followed to gain insight into the thrombogenic potential on this protein and inspire new strategies against thrombotic complications of atherosclerosis. PMID- 1505659 TI - IDL, VLDL, chylomicrons and atherosclerosis. AB - In humans with the lipoprotein lipase deficiency disorder large amounts of chylomicrons and large very low-density lipoprotein (VLDL) accumulate in plasma. In spite of this, atherosclerosis does not seem to develop at an accelerated rate, suggesting that these lipoproteins do not promote atherogenesis. In humans with dysbetalipoproteinemia remnant lipoproteins (intermediate density lipoprotein (IDL) plus beta-VLDL) accumulate in plasma and these particles may therefore be the factor causing accelerated atherosclerosis in this disorder. Epidemiological studies in humans suggest that IDL or remnant lipoproteins are predictors of the severity or progression of atherosclerosis. Similar studies in the St. Thomas' Hospital rabbit strain, an animal model with genetically elevated plasma levels of VLDL, IDL and low-density lipoprotein (LDL), showed that IDL or remnant lipoproteins were better predictors of the extent of atherosclerosis than were LDL or VLDL. Studies of lipoprotein/arterial wall interactions have demonstrated that the larger the lipoprotein particle, the lower the influx into intima. Very large VLDL and chylomicrons do not seem to enter intima. Although high-density lipoprotein (HDL) enters intima faster than other lipoproteins, the small HDL particles seem to penetrate the entire arterial wall and leave via lymphatics and vasa vasorum in the outer media and adventitia. In contrast, LDL, and possibly also IDL and smaller VLDL, may only leave the intima via the lumen of the artery. In conclusion, a substantial body of evidence suggests that remnant lipoproteins (IDL and smaller VLDL) share with LDL the potential for promoting atherosclerosis, whereas very large VLDL and chylomicrons do not seem to have this effect. PMID- 1505660 TI - The importance of triglycerides: results from the Prospective Cardiovascular Munster (PROCAM) Study. AB - In the PROCAM study hypertriglyceridaemia was much more common among men (18.6%) than women (4.2%). Prevalence increased with age in women, but remained nearly constant at about 20% in men aged 35 years or more. In a multiple regression analysis a strong negative correlation between triglycerides and HDL cholesterol was found. A positive relationship was observed with cholesterol, blood glucose, factor VIIc, and PAI-1 in both sexes. Only in men, triglycerides are positively correlated with Apo A-I, body mass index, cigarette smoking, and alcohol consumption. Postmenopausal women showed higher triglyceride levels than premenopausal women. No independent relationships were observed to age, blood pressure, Lp(a), Apo A-II, Apo B, AT-III, protein C, fibrinogen, and oral contraceptives. A longitudinal analysis of data from 4474 male PROCAM participants aged 40-64 years with a follow-up of 4 years did not identify triglycerides as an independent risk factor, but the data suggest hypertriglyceridaemia is an additional risk factor for CHD, when excessive triglycerides coincide with a high ratio of plasma cholesterol to HDL-cholesterol and with low HDL-cholesterol values. PMID- 1505661 TI - Protein engineering of Drosophila alcohol dehydrogenase. The hydroxyl group of Tyr152 is involved in the active site of the enzyme. AB - Drosophila alcohol dehydrogenase is the most studied member of the family of short-chain alcohol dehydrogenases, although its tridimensional structure still remains unknown. We have engineered a Drosophila alcohol dehydrogenase in which tyrosine-152, an invariant residue in all members of the family, has been substituted by phenylalanine. The mutated gene has been expressed in yeast and pure mutant enzyme has been prepared by a one-step FPLC chromatographic procedure. Drosophila alcohol dehydrogenase-phenylalanine-152 shows no enzymatic activity. This result suggests not only that tyrosine-152 could constitute an essential building block of the active site but also that its hydroxyl group is directly involved in the redox reaction catalyzed by the enzyme. PMID- 1505662 TI - Regions of beta 4.beta 2 subunit chimeras that contribute to the agonist selectivity of neuronal nicotinic receptors. AB - Fifteen chimeric nicotinic receptor beta subunits were constructed consisting of N-terminal neuronal beta 4 sequences and C-terminal beta 2 sequences. Responses to cytisine, nicotine, or tetramethylammonium were compared to acetylcholine responses for these subunits expressed in Xenopus oocytes with alpha 3 subunits. The results show that (i) two residues in the extracellular domain of chimeric beta 4.beta 2 subunits (108 beta 2F/beta 4V, 110 beta 2S/beta 4T) account for much of the relative cytisine sensitivity; and (ii) four extracellular residues of chimeric beta 4.beta 2 subunits (112 beta 2A/beta 4V, 113 beta 2V/beta 4I and 115 beta 2S/beta 4R, 116 beta 2Y/beta 4S) account for most of the relative tetramethylammonium sensitivity. The data did not permit localization of nicotine sensitivity to any particular region. PMID- 1505663 TI - Tobacco chloroplast ribosomes contain a homologue of E. coli ribosomal protein L28. AB - The genes for ribosomal proteins L28 and L33 constitute an operon (rpmBG) in E. coli, but in plant chloroplasts L33 is encoded by the chloroplast DNA and L28 seems to be encoded by the nuclear genome. A 15 kDa protein was isolated from the 50 S subunit of tobacco chloroplast ribosomes and its N-terminal amino acid sequence was determined. A cDNA for this protein was cloned and analyzed. The cDNA encodes a 151 amino acid protein consisting of a predicted transit-peptide of 74 amino acids and a mature protein of 77 amino acids. The mature protein is homologous to E. coli L28, hence we named it chloroplast L28 (CL28). This is the first report on the presence of an E. coli L28-like protein in another organism. PMID- 1505664 TI - Synthesis of the proline analogue [2,3-3H]azetidine-2-carboxylic acid. Uptake and incorporation in Arabidopsis thaliana and Escherichia coli. AB - Azetidine-2-carboxylic acid, the 4-membered ring noranalogue of proline, is regularly used in the study of proline metabolism as well as the study of protein conformation. We prepared D,L-[2,3-3H]azetidine-2-carboxylic acid with an optimized 10% yield from commercially available 4-amino-[2,3-3H]butyric acid. Purification was performed by fast-protein liquid chromatography. The biological activity was checked in both Arabidopsis thaliana and Escherichia coli. The obtained specific activity of 10 mCi/mmol was sufficient for most uptake and incorporation studies. PMID- 1505665 TI - Vitamin E dietary supplementation inhibits transforming growth factor beta 1 gene expression in the rat liver. AB - Overexpression of transforming growth factor beta 1 (TGF beta 1) and increased transcription of pro-collagen type I, are known to represent major events implicated in the development of liver fibrosis under either experimental or clinical conditions. Here we report that long-term dietary vitamin E supplementation in animals undergoing an experimental model of liver fibrosis (induced by chronic treatment of rats with carbon tetrachloride) results in a net inhibition of both hepatic TGF beta 1 and alpha 2 (I) procollagen mRNA levels. Moreover, of striking interest is the observation that vitamin E supplementation per so down-modulates basal levels of TGF beta 1 mRNA in the liver of untreated animals, suggesting that a dietary regimen rich in vitamin E may potentially interfere with both the initiation and progression of the fibrosclerotic processes. PMID- 1505666 TI - Trimethylamine dehydrogenase of bacterium W3A1. Molecular cloning, sequence determination and over-expression of the gene. AB - The gene encoding trimethylamine dehydrogenase (EC 1.5.99.7) from bacterium W3A1 has been cloned. Using the polymerase chain reaction a 530 bp DNA fragment encoding a distal part of the gene was amplified. Using this fragment of DNA as a probe, a clone was then isolated as a 4.5 kb BamHI fragment and shown to encode residues 34 to 729 of trimethylamine dehydrogenase. The polymerase chain reaction was used also to isolate the DNA encoding the missing N-terminal part of the gene. The complete open reading frame contained 2,190 base pairs coding for the processed protein of 729 amino acids which lacks the N-terminal methionine residue. The high-level expression of the gene in Escherichia coli was achieved by the construction of an expression vector derived from the plasmid pKK223-3. The cloning and sequence analysis described here complete the partial assignment of the amino acid sequence derived from chemical sequence [1] and will now permit the refinement of the crystallographic structure of trimethylamine dehydrogenase and also a detailed investigation of the mechanism and properties of the enzyme by protein engineering. PMID- 1505667 TI - Flow-induced prostacyclin production is mediated by a pertussis toxin-sensitive G protein. AB - Fluid flow and several other agonists induce prostacyclin (PGI2) production in endothelial cells. G proteins mediate the response of a large number of hormones such as histamine, but the transduction pathway of the flow signal is unclear. We found that GDP beta S and pertussis toxin inhibited flow-induced prostacyclin production in human umbilical vein endothelial cells. In addition, flow potentiated the histamine-induced production of PGI2. This suggests that flow stimulates prostacyclin production via a pertussis toxin-sensitive G protein and modulates the stimulus-response coupling of other agonists. PMID- 1505668 TI - Molecular cloning and permanent expression in a neuroblastoma cell line of a fast inactivating potassium channel from bovine adrenal medulla. AB - Using a cDNA library from bovine adrenal medulla, we have isolated cDNAs coding for a potassium channel. These cDNAs encode a 660-amino acid protein that has a molecular weight of 73,288 kDa and no amino-terminal signal peptide. We have called it BAK4. Analysis of its sequence reveals close similarity (94% homology) with a recently described potassium channel from rat brain (RCK4) and heart (RHK1). Neuroblastoma cells (Neuro-2a cell line) were stably transfected with BAK4 DNA. Expression of the DNA was under the control of a heat-shock promoter. Several clones, that were isolated by neomycin resistance selection, had integrated the plasmid DNA in a stable form. Upon heat induction, these cells produced BAK4 RNA and a potassium outward current, not present in control non transfected cells. The current, which was transient and decayed markedly during the duration of 200 ms-pulses, can be described as a Ik(A) potassium current. The expression of these types of channels in brain (RCK4,RHK1), heart (RHK1) and adrenal medulla (BAK4) suggest their possible implication in important functions for the cell. PMID- 1505669 TI - Specific release of a 9-kDa extrinsic polypeptide of photosystem I from spinach chloroplasts by salt washing. AB - The newly reported 9-kDa polypeptide in photosystem I [(1991) FEBS Lett. 280, 332 334] is an extrinsic component located on the lumenal side of the thylakoid membrane. This subunit can be solubilized with high salt buffer and does not bind any cofactors. The photosystem I electron transfer chain remains intact and functional in the absence of this component as characterized by the photoreduction of NADP+. PMID- 1505670 TI - Quantitative study of the binding of cysteine proteinases to basement membranes. AB - Binding of cysteine proteinases of the papain superfamily (papain and cathepsins B, B-like and L) to basement membranes was studied by using the enzymatic activity of these proteinases against their specific fluorogenic substrates. Papain inactivated by E64 was used for Kd determination by competition experiments. The binding was characterized using the following parameters, the equilibrium constant, Kd, and the number of substrate sites, n, values of which were in the range of 10(-7) M and 10(12), respectively. Such results would be of significant interest for the understanding of the biological role of cysteine proteinases in tumour invasion and other types of tissue remodeling. PMID- 1505671 TI - Characterization of myocardial extracellular ATP receptors by photoaffinity labelling and functional assays. AB - Extracellular ATP receptors in rat ventricular myocytes were investigated through intact cell photolabelling followed by protein isolation. 8-Azido-ATP (8Az-ATP) was used for labelling under specific conditions determined by parallel functional studies. In those studies ATP-induced cytosolic Ca2+ transients were irreversibly and specifically inhibited by UV-photolyzed 8Az-ATP, but not by 2 azido-ATP (2Az-ATP), even in the presence of high concentrations of phosphonucleotides not affecting myocardial ATP receptors. Under those conditions background labelling is minimized and radioactive 8Az-ATP specifically labels a band of 45-48 kDa on a SDS gel. Labelling under the above conditions in the presence of ATP gamma S or 2-methylthio-ATP (2-meSATP), which are distinct for two functionally different cardiac ATP receptors, shows two different proteins within the same band consistent with the possible labelling of these two receptors. PMID- 1505672 TI - Lipid interaction of tetanus neurotoxin. A calorimetric and fluorescence spectroscopy study. AB - The interaction of Tetanus toxin with phospholipid vesicles containing gangliosides (GD1a, GD1b or GT1b) or phosphatidic acid has been investigated at neutral or acidic pH. Change in the thermotropic properties of the vesicles occurred only after addition of the toxin at acidic pH, and led to surface binding or membrane insertion of the protein, dependent on the physical state of the membrane. Most remarkably, toxin addition at acidic pH to dipalmitoyl phosphatidylcholine vesicles containing GT1b ganglioside, caused formation of ganglioside microdomains on the vesicle surface. PMID- 1505673 TI - Relocalization of alpha B-crystallin by heat shock in ovarian carcinoma cells. AB - alpha B-Crystallin, a major lens protein, is present in clearly detectable amounts in cultured ovarian carcinoma cells. After heat-shock treatment of these cells at 45 degrees C alpha B-crystallin relocalizes from the detergent-soluble, cytosolic fraction to the non-ionic detergent-insoluble nuclear/cytoskeletal fraction. Colchicine treatment of the cells, although giving rise to a vimentin collapse on the nucleus, does not result in redistribution of alpha B-cyrstallin. When this colchicine treatment is followed by heat shock, alpha B-crystallin relocalizes again to the insoluble fraction, indicating that this relocalization is independent of the collapse of the vimentin network. PMID- 1505674 TI - The complete primary structure of abrin-a B chain. AB - The complete 267 amino acid sequence of abrin-a B chain was determined by analysis of peptides obtained by digestion with trypsin, chymotrypsin, lysyl endopeptidase, Staphylococcus aureus V8 protease and thermolysin. The sequence is not identical with that predicted previously by nucleotide sequencing, indicating the presence of isoforms of abrin. Comparison of the amino acid sequence of abrin a B chain with that of ricin-D B chain reveals a high degree of sequence identity (59%). Abrin-a B chain appears to consist of two domains, each domain with subdomains (alpha, beta, gamma) of about 40 amino acid residues. PMID- 1505675 TI - Structure of the small ribosomal subunit RNA of the pulmonate snail, Limicolaria kambeul, and phylogenetic analysis of the Metazoa. AB - The complete nucleotide sequence of the small ribosomal subunit RNA of the gastropod, Limicolaria kambeul, was determined and used to infer a secondary structure model. In order to clarify the phylogenetic position of the Mollusca among the Metazoa, an evolutionary tree was constructed by neighbor-joining, starting from an alignment of small ribosomal subunit RNA sequences. The Mollusca appear to be a monophyletic group, related to Arthropoda and Chordata in an unresolved trichotomy. PMID- 1505676 TI - TATA box-independent transcription of the human tissue plasminogen activator gene initiates within a sequence conserved in related genes. AB - Transcription of the human tissue-type plasminogen activator (tPA) gene has been reported to initiate from a single site proximal to a TATA box motif [1985, J. Biol. Chem. 260, 11223-11230]. In this study, we utilized primer extension analysis to evaluate the tPA mRNA start site in phorbol-12-myristate 13-acetate (PMA) induced WI-38 human lung fibroblast cells. Whilst some tPA mRNA initiated from the predicted TATA-proximal location (+1), a 10-fold greater proportion of tPA mRNA transcripts initiated 110 bases downstream from a sequence conserved and utilized as the TATA-independent transcription start site in the rodent tPA genes. Moreover, the transfection and expression in different cell types of a cosmid containing the entire human tPA gene resulted in utilization of the same downstream (+110) start site. We propose that this, rather than the previously published position, is the major transcriptional initiation point for the human tPA gene. A core sequence (5'-CAGAGCTG-3') was identified which is common to the TATA-independent mRNA start sites of the human, mouse and rat tPA genes, and which demonstrates only partial similarity to sequences found at the initiation point of other TATA-independent genes. PMID- 1505677 TI - A protective role for nitric oxide in the oxidative modification of low density lipoproteins by mouse macrophages. AB - Low density lipoproteins (LDL) oxidatively modified by macrophages have been shown to be atherogenic in ex vivo studies. We studied the potential role of nitric oxide (NO), a free radical produced by macrophages, in LDL modification. Human LDL (1 mg/ml) were incubated with mouse peritoneal macrophages in Ham's F 10 medium. The cells were then stimulated by interferon-gamma and tumor necrosis factor-alpha to increase their production of NO from 1.3 to 12.2 microM in 24 h, as measured by nitrite. Lipid peroxidation of LDL, as measured by thiobarbituric acid-reactive materials (TBARS), was reduced in stimulated cells in a time dependent manner. At 24 h, the decrease was about 27%. In the presence of an NO synthase inhibitor (NG-aminophomoarginine), the generation of NO was diminished and the protection against LDL lipid peroxidation was reversed. The extent of LDL protein modification was also assessed by examining its electrophoretic mobility. It was found that macrophage NO reduced the change in LDL electromobility. These data indicate that the production of NO may inhibit the oxidative modification of LDL with cytokine-stimulated macrophages. We suggest that NO plays a protective role in limiting macrophage-induced LDL modification. PMID- 1505678 TI - X-ray crystal structure of the serine proteinase inhibitor eglin c at 1.95 A resolution. AB - The crystal structure of eglin c, naturally occurring in the leech Hirudo medicinalis, is known from its complexes with various serine proteinases, but the crystallization of free eglin c has not yet been reported. A method is described for growing well-diffracting crystals of free eglin c from highly concentrated protein solutions (approximately 200 mg/ml). The space group of the orthorhombic crystals was determined to be P2(1)2(1)2(1) with unit cell parameters a = 32.6, b = 42.0, c = 44.1 A. The structure of free eglin c was resolved at 1.95 A resolution by Patterson search methods. The final model contains all 70 amino acids of eglin c and 125 water molecules. In comparison to the eglin structure known from its complexes with proteinases, only small differences have been observed in free eglin c. However, the reactive site-binding loop and a few residues on the surface of eglin have been found in different conformations due to crystal contacts. In contrast to the complex structures, the first seven amino acids of the highly flexible amino terminus can be located. Crystallographic refinement comprised molecular dynamics refinement, classical restrained least squares refinement and individual isotropic atomic temperature refinement. The final R-factor is 15.8%. PMID- 1505679 TI - Insulin receptor and glucose transporter mRNA expression in skeletal muscle of genetically obese Zucker rats. AB - Insulin resistance and defective glucose transport are associated with muscle tissue in the genetically obese Zucker rat and are accompanied by changes in the number of insulin receptors and the availability of glucose transporters. The present study was carried out to assess whether, in male Zucker rats at 10 weeks of age, these defects were reflected by changes in the levels of mRNAs for the insulin receptor and for the insulin responsive glucose transporter (GLUT-4). Total RNA was extracted from plantaris and soleus muscles and the levels of insulin receptor and GLUT-4 mRNAs and 18 S rRNA were determined by Northern hybridization and quantified by image analysis of the autoradiographs. A 50% increase in the level of insulin receptor mRNA was detected in both the plantaris and the soleus muscle from the obese rats compared to the lean rats. No change in the level of GLUT-4 mRNA was detected in the plantaris muscle although increases were observed in the soleus muscle from the obese rats. PMID- 1505680 TI - Characterization of a 41 kDa photoinhibition adduct in isolated photosystem II reaction centres. AB - When isolated reaction centres of photosystem II are subjected to photoinhibitory illumination, a 41 kDa SDS-PAGE band is observed under all experimental conditions. The same band is also found, together with lower molecular weight fragments of the D1 protein, in whole thylakoids and in all PSII sub-particles investigated up to now. In the case of isolated reaction centres the 41 kDa band is represented by a heterodimer of the D1 polypeptide and the alpha-subunit of cytochrome b559. The cross-linkage between D1 and alpha-cyt b559 involves a region on D1 between the N-terminal residue and Arg-225, and is an early event in photo-induced damage to the D1 protein. PMID- 1505681 TI - Occupancy of a C2-C2 type 'zinc-finger' protein domain by copper. Direct observation by electrospray ionization mass spectrometry. AB - The metal ion specificity of most 'zinc-finger' metal binding domains is unknown. The human estrogen receptor protein contains two different C2-C2 type 'zinc finger' sequences within its DNA-binding domain (ERDBD). Copper inhibits the function of this protein by mechanisms which remain unclear. We have used electrospray ionization mass spectrometry to evaluate directly the 71-residue ERDBD (K180-M250) in the absence and presence of Cu(II) ions. The ERDBD showed a high affinity for Cu and was completely occupied with 4 Cu bound; each Cu ion was evidently bound to only two ligand residues (net loss of only 2 Da per bound Cu). The Cu binding stoichiometry was confirmed by atomic absorption. These results (i) provide the first direct physical evidence for the ability of the estrogen receptor DNA-binding domain to bind Cu and (ii) document a twofold difference in the Zn- and Cu-binding capacity. Differences in the ERDBD domain structure with bound Zn and Cu are predicted. Given the relative intracellular contents of Zn and Cu, our findings demonstrate the need to investigate further the Cu occupancy of this and other zinc-finger domains both in vitro and in vivo. PMID- 1505682 TI - Reactive oxygen species are involved in the activation of cellular phospholipase A2. AB - Vanadate (V) potentiated (4- to 10-fold) the activation of cellular phospholipase A2 (PLA2) induced by H2O2 (H), a phorbol ester (T), a Ca(2+)-ionophore (A) and opsonized zymosan in macrophages. V+H induced in intact cells the activation and translocation of PLA2 and protein kinase C (PKC) to the plasma membrane. V+H and V+T+A induced strong chemiluminescence (CL) which was abrogated by a specific NADPH oxidase inhibitor diphenylene iodonium (DPI). DPI markedly suppressed the stimulation of PLA2 by V+T+A and V+OZ. The results suggest that the formation of endogenous reactive oxygen species (ROS) is important for PLA2 activation. PMID- 1505683 TI - The microtubule binding repeats of tau protein assemble into filaments like those found in Alzheimer's disease. AB - The paired helical filament, which comprises the major fibrous element of the neurofibrillary tangle in Alzheimer's disease, contains abnormally phosphorylated microtubule-associated protein tau as its principal constituent. The repeat region of tau protein, which represents the microtubule binding domain, forms the core of the filament. Here we show that an expressed fragment of tau protein spanning the repeat region can assemble in vitro into filaments like those found in Alzheimer's disease. PMID- 1505684 TI - Molecular cloning of the alpha-subunit of rat endopeptidase-24.18 (endopeptidase 2) and co-localization with endopeptidase-24.11 in rat kidney by in situ hybridization. AB - Endopeptidase-24.18 (endopeptidase-2, EC 3.4.24.18, E-24.18) is a Zn-ectoenzyme of rat renal and intestinal microvillar membranes exhibiting an oligomeric structure, alpha 2-beta 2. The primary structure of the alpha-subunit of E-24.18 has been defined by molecular cloning and its expression mapped in rat kidney by in situ hybridization. A 2.9-kb cDNA coding for the alpha-subunit was isolated and sequenced. It had an open reading frame of 2,244 base pairs coding for a type I membrane protein of 748 amino acids. The deduced amino acid sequence showed 87% identity with that of meprin A, a mouse metallo-endopeptidase, sharing common properties with the rat enzyme, and 85% identity with the human intestinal enzyme, 'PABA-peptide hydrolase'. Northern blot analysis revealed the alpha subunit to be encoded by a single mRNA species of 3.2-kb. In situ hybridization performed on rat kidney showed a co-localization of E-24.18 with endopeptidase 24.11 in proximal tubules of juxtamedullary nephrons, suggesting that the two enzymes have similar or complementary physiological functions in kidney. PMID- 1505685 TI - Vanadate potentiates the glycogenic action of insulin-like growth factors on isolated diaphragm. AB - Na3VO4 (6.5 mumol/100 g rat weight), co-injected with a trace amount of [14C]glucose, increased within 15 min the incorporation of radiolabel in diaphragmal glycogen. After 2 h the vanadate-induced increases were 12-fold in the diaphragm and 7-8-fold in heart and liver. In contrast, when added to isolated diaphragms for up to 1 h, vanadate (0.1-5 mM) had no effect on the synthesis of glycogen from 5 mM glucose. In search of a putative mediator of vanadate's action in vivo, insulin and the insulin-like growth factors (IGFs) were considered. Their plasma concentration was not affected by vanadate treatment. In isolated diaphragms, 1 mM vanadate did not potentiate insulin induced glycogen synthesis, but it caused a several-fold increase in glycogen synthesis in the presence of concentrations of IGF-I which, alone, had no effect. A similar synergism occurred between vanadate and IGF-II. We propose that the glycogenic action of vanadate in vivo, at least in some tissues, involves a potentiation of the action of IGF-I. PMID- 1505686 TI - Fourier transform infrared (FTIR) spectroscopic investigation of the nicotinic acetylcholine receptor (nAChR). Investigation of agonist binding and receptor conformational changes by flash-induced release of 'caged' carbamoylcholine. AB - The binding and interaction of carbamoylcholine with the nicotinic acetylcholine receptor was investigated using photolytically released carbamoylcholine ('caged' carbamoylcholine). Upon UV flash activation of this photolabile substrate analog, characteristic changes in the IR absorbance spectrum were detected. Apart from difference bands arising from the changes of molecular structure upon photolytical release, spectral features can be attributed to the agonist upon binding to the receptor as well as to conformational changes of the receptor itself. The two photo-labile agonist analogs N-[1-(2-nitrophenyl)ethyl] carbamoylcholine iodide (cage I) and N-(alpha-carboxy-2-nitrobenzyl) carbamoylcholine trifluoroacetate (cage II), with different structures for comparison of the 1680-1540 cm-1 region sensitive for protein conformation, yielded consistent results. A preliminary interpretation in terms of substrate binding and local conformational changes of the receptor upon carbamoylcholine binding is provided, in analogy to the binding of acetylcholine, activation, and subsequent deactivation taking place during signal transduction. PMID- 1505687 TI - Adaptability of the coccidian Coelotropha to parasitism. AB - The coccidian, Coelotropha durchoni, manages to develop in its host, the polycheate annelid, Nereis diversicolor, because of its ability to circumvent the host's internal defence system. First, it avoids phagocytes by penetrating other cells, principally eleocytes and muscular cells, where it undergoes a phase of intracellular development. After becoming extracellular, a thick coat protects it from being attacked by granulocytes. This coat then breaks and is shed from its surface to permit fertilization. Parasites that have lost their coats and remain unfertilized are surrounded with granulocytes and destroyed by encapsulation. A strict hormonal correlation exists between the biological cycles of the parasite and its host. Thus, the mature spores of the coccidian parasite are disseminated when the worm lays its gametes by rupture of teguments. C. durchoni and N. diversicolor have established a biological equilibrium that permits mutual survival of both partners and constitutes a simple model for the study of the host-parasite relationship. PMID- 1505688 TI - Allogeneic resorption in colonial protochordates: consequences of nonself recognition. AB - Colonial tunicates (protochordates of the subfamily Botryllinae) have the property of forming natural chimeras in the wild or in the laboratory with other members of the same species if both individuals share at least one allele at a single highly polymorphic locus, termed the fusibility/histocompatibility (Fu/HC) locus. Laboratory studies revealed that after the establishment of a common blood circulatory system between a fusible pair one of the colonies in the chimera is usually resorbed, a phenomenon that occurs after an interval of 1 week or extends to up to 8 months. In the present article, we review this allogeneic resorption in Botryllus schlosseri, a cosmopolitan protochordate. The studies on allogeneic resorption in B. schlosseri revealed 13 typical characteristics. However, several processes interrupt successful resorption, such as the retreat growth phenomenon, chimeric death, and others. It was also found that allogeneic resorption is not only genetically controlled but is also controlled by a polymorphic hierarchial phenomenon, including the Fu/HC locus and additional unrelated loci. One basic rule for this genetic system is that colonies heterozygotic on the resorption elements will resorb more homozygotic partners. This colony resorption, expressed by a morphological elimination of one partner, is probably manifested by cellular elements circulating in the tunicate blood system. However, it was also shown that some blood-borne cells of the inferior partner, such as the stem cells, may escape resorption, a phenomenon that raises the threat of germ/somatic cell parasitism. PMID- 1505689 TI - Phagocytosis and hydrogen peroxide production by phagocytes of the sea urchin Strongylocentrotus nudus. AB - Phagocytosis of erythrocytes by phagocytes from the sea urchin Strongylocentrotus nudus can occur in vitro, and is enhanced by opsonization with the coelomic fluid. This opsonic activity of coelomic fluid can be elevated over a 5-day period by injecting erythrocytes into the coelom. Phagocytes produce hydrogen peroxide during both resting and stimulated states. This result on hydrogen peroxide production is the first to be observed in echinoderms. During the stimulated state, phagocytes produce more hydrogen peroxide than resting phagocytes. However, hydrogen peroxide production by phagocytes is not affected by opsonic activity of the coelomic fluid. Phagocytes share similar functional properties with vertebrate macrophages and granulocytes. PMID- 1505690 TI - Identification of a second immunoglobulin in the most primitive shark, the frill shark, Chlamydoselachus anguineus. AB - Three molecular forms of immunoglobulins: pentamer, dimer and monomer, were isolated from serum of the frill shark, Chlamydoselachus anguineus, the most primitive extant shark. A pentamer having an apparent mass of 900 kDa, consisting of 68 kDa heavy (H) chains and 22-24 kDa light (L) chains, was considered to be IgM because of its similarity to mammalian IgM in both molecular form and H chain molecular weight. The dimer and monomer with apparent masses of 300 kDa and 150 kDa, respectively, were composed of the same H chains of 45-50 kDa, a value smaller than that of the H chains from the pentamer, and light chains identical to those of the pentamer. The H chains of 68 kDa and 45-50 kDa represented individual epitopes and were synthesized by different plasma cells. We thus concluded that the frill shark has two distinct classes of immunoglobulins: one a pentameric IgM and the other a second class of immunoglobulin with dimeric and monomeric structure. The presence of the second Ig is of considerable interest with respect to antigen recognition and exclusion. PMID- 1505691 TI - The cellular proliferative response, humoral antibody response, and cross reactivity studies of Tetrahymena pyriformis with Ichthyophthirius multifiliis in juvenile carp (Cyprinus carpio L.). AB - The immune response of 10-12-week-old juvenile carp to T. pyriformis [CCAP 1630/w, 1939 (w)] was investigated. The humoral antibody response following one and two intraperitoneal injections of whole live T. pyriformis (protein concentration of 25 micrograms/g body weight), separated by an interval of 4 weeks, was monitored over 12-16 weeks. Peak antibody titres were detected 6 weeks following antigen administration. Antibody titres were elevated following the second injection, and relatively high levels were still maintained by week 16. Proliferative responses measured by autoradiography following intraperitioneal injection of methyl 3H thymidine (1-2 microCi/g body weight) were recorded in the pronephros, opisthonephros, and spleen at weekly intervals for 4 weeks following each injection of T. pyriformis. Immunised fish had higher counts than nonimmunised controls, with the greatest counts occurring at 2 and/or 3 weeks following one injection of antigen and 2 weeks following two injections. Activity was recorded prior to peak antibody production with the pronephros and opisthonephros having greater proliferative responses than the spleen. Cross antigenicity studies to examine protection of carp against I. multifiliis following administration of T. pyriformis, showed little evidence in support of protection using this strain of T. pyriformis. Further, antisera raised in either carp, rabbits, or rats failed to show any cross antigenicity between these two species of protozoa. PMID- 1505692 TI - The effects of MHC chromosome dosage on bursal B-cell subpopulations in embryonic and neonatal chickens. AB - The effect of MHC dosage on the population structure of developing bursal lymphocytes was studied in the Trisomic strain of chickens. These chickens contain either 2 (disomic), 3 (trisomic), or 4 (tetrasomic) copies of the MHC encoding chromosome. To assess the developmental profile of bursal cell populations, bursal cells were characterized in the older embryo (18 days of incubation) and at two neonatal ages (1 day and 1 week post hatch) by a number of cellular parameters. Both transient and persistent alterations in cellular composition were revealed in the bursal subpopulations of trisomics and tetrasomics (aneuploids). Aneuploid bursal cells showed increased cell surface expression of MHC class II Ia antigen, at each age, compared to normal disomic cells. Aneuploid cell populations showed an increased incidence of small cells, at each age, a decreased incidence of Ia+ and IgM+ cells during late embryogenesis, and an increased incidence of IgG+ cells in the late embryo and 1 day-old chick. Significantly fewer proliferating cells were observed in the aneuploids, as compared to disomics, in the late embryo and 1-week-old chick. Three subpopulations were observed to be persistently altered in the MHC aneuploids: an increased pool of Ia , small, IgM+ cells; a decreased pool of Ia+, large, IgM+ cells; and a decreased pool of Ia+, large, IgM- cells. Thus, increasing MHC-chromosome dosage is accompanied by specific alterations in B-cell differentiation. The elevated surface Ia antigen expression found on developing aneuploid B cells may play a role in these alterations. PMID- 1505693 TI - Characterization of a cDNA clone encoding for a porcine immunoglobulin mu chain. AB - We present the complete sequence of cDNA clone BLM6, isolated from a porcine spleen cDNA library. BLM6 encodes for the constant region of a secreted mu heavy chain. The cDNA is 1342 bp in length, begins within C mu 1, and terminates in the 3' translated region. The deduced amino acid sequence indicates there are 111 amino acids in C mu 2, 106 in C mu 3, and 113 in C mu 4, along with 19 carboxy terminal residues that comprise the secreted terminus. The full length transcript is approximately 2.4 kb as determined by Northern blot analysis. Southern blot analysis suggests there is only one mu chain gene within the porcine genome. Comparison of the deduced amino acid sequence of porcine C mu with other mammalian C mu sequences indicates that the overall identity is approximately 60%, with the greatest identity seen in the secreted terminus (approximately 85%) and C mu 4 (approximately 70%); and less identity in C mu 3 (60%) and C mu 2 (50%). PMID- 1505695 TI - Abstracts of the 28th annual meeting of the European Association for the Study of Diabetes. Prague, Czechoslovakia, 8-11 September 1992. PMID- 1505696 TI - Medicine as storytelling. PMID- 1505694 TI - Effects of ammonium chloride on microbicidal activity in hemocytes of Biomphalaria glabrata (Mollusca: Pulmonata). PMID- 1505697 TI - Euthanasia and assisted suicide. I. How often is it practised by family doctors in The Netherlands? AB - A survey was conducted among family doctors to determine the frequency with which they were requested to administer euthanasia or assist in suicide, and how often they actually applied these procedures. Two random samples (in each n = 521) were taken from the population of Dutch family doctors (n = 6300) and requested to complete an anonymous questionnaire. The response was 67%. The entire body of Dutch family doctors practices euthanasia or assisted suicide about 2000 times per annum; 48% have never engaged in these practices. An average of 40% of all requests are complied with. We conclude that far fewer family doctors are involved in euthanasia and assisted suicide than was previously supposed. Euthanasia or assisted suicide was administered to 1 in 25 persons who died in their own homes. PMID- 1505699 TI - Experience of bereaved relatives who granted or refused permission for organ donation. AB - A group of individuals who had granted or refused permission to have organs removed from a decreased relative for transplantation were interviewed. Organ donation was found to be a very delicate subject: the request for organ donation often comes unexpectedly and most relatives are not aware of the wishes of the decreased (donor codicil), which complicates the decision process. Some of the relatives who refused regretted their decision later. Remorse was also encountered in the group who gave their permission, although positive feelings were more common. The position of the member of staff who asks for permission is complicated. Suggestions are presented to improve the procedure. PMID- 1505698 TI - Euthanasia and assisted suicide. II. Do Dutch family doctors act prudently? AB - We conducted a survey among two random samples of Dutch doctors in order to determine whether they acted prudently with regard to euthanasia and assisted suicide. The doctors completed an anonymous questionnaire and those who at one time or another had applied euthanasia or assisted suicide (52%) were asked about several aspects of the requirements for prudent practice. 'Pointless suffering' was the most important and most common reason for requesting euthanasia or assisted suicide; 'pain' was rarely the most important reason. In 7% of the cases alternative forms of treatment were still available; these were hardly ever therapeutic. A total of 12% of the doctors had applied euthanasia or assisted suicide without having had any kind of consultation or discussion with a colleague, a nurse or any other health care professional; 26% had not issued a certificate testifying to death from natural causes. We conclude that some of the family doctors do not observe the procedural requirements, but that the majority satisfies the material requirements for prudent practice. PMID- 1505700 TI - Overall use of proctoscopy in general practice and possible relation to the stage of rectal cancer. AB - Data from the Danish National Health Service records on activities of each of 146 general practices in the county of North Jutland, Denmark, were studied to determine whether the use of proctoscopy influenced the stage at which cancer of the rectum was recognized. Information for all patients in the county who received the diagnosis of cancer of the rectum was obtained from the Danish Cancer Registry. Proctoscopy was performed significantly more often in partnership practices (96%) than in single practices (81%). The frequency with which the test was used varied from 1 to 107 proctoscopies per general practitioner per year. In the 95 patients with cancer of the rectum, no relationship was found between the stage (Dukes') at the time of diagnosis and work-load, size and activity of practice, or use of proctoscopy. PMID- 1505701 TI - Evaluating patients with chest pain using classification and regression trees. AB - We collected data on 320 patients complaining to their general practitioner of a new episode of chest pain, discomfort or oppression. Relationships were examined between initial signs and symptoms and a follow-up diagnosis after a period of 2 weeks to 2 months. The data were analysed with CART, a statistical decision theory software package. In our first run, the number of misclassifications by CART was 56%. After regrouping of the data and diagnostic categories, there were 37% misclassifications. The most discriminating variable turned out to be pain on palpation. When comparing each of five diagnostic groups to all others, we found a positive predictive value of 27% for gastrointestinal diseases, 72% for cardiovascular disorders, 69% for respiratory diseases, 58% for psychopathology and 73% for chest wall pathology. The CART methodology needs further investigation and testing before any clinical application will be possible in general practice. PMID- 1505702 TI - An evaluation of a nurse-run asthma clinic in general practice using an attitudes and morbidity questionnaire. AB - A before and after longitudinal study was conducted to evaluate a nurse-run asthma clinic in general practice. Sibbalds morbidity and attitudes questionnaire was used to monitor the changes in association with attendance at the clinic. One hundred and five patients aged 3-83 years attended the clinic. Over the 12 months of the study patients reported significant reductions in attacks of wheeze, nocturnal attacks, overall trouble (P eta 0.005) and GP home visits (P = 0.02). Patients also reported a significant improvement in feelings of stigma (P less than 0.001), and confidence in self-care (P less than 0.001). There was a significant association between morbidity criteria such as 'overall interference' and stigma at the outset of the clinic (R = -0.44; P less than 0.001; 95% confidence interval -0.58 to -0.26). A patient's feelings of stigma towards their asthma at the outset did not predict the eventual improvement in morbidity. As the patient's asthma improved the feelings of stigma became less apparent. This would suggest that improving a patient's morbidity should be one of the first priorities in asthma care. Confidence in the doctor was high at the outset and did not change throughout the study, despite the fact that a large proportion of patients wanted more information about their asthma but found it difficult to talk to their doctor. General practitioners are often restrained by how much time and resources they can devote to each patient. The nurse-run asthma clinic with its programme of structured care represents a possible solution to these problems. PMID- 1505703 TI - Treatment with inhaled steroids in asthma and chronic bronchitis: long-term compliance and inhaler technique. AB - We investigated compliance and inhaler technique in 50 patients with airway obstruction (26 asthma, 24 chronic bronchitis) being treated with inhaled steroid (beclomethasone dipropionate, BDP) via a dry powder inhaler (Rotahaler omega). Patients had already participated for one year in a 2-year trial of BDP in general practice. They were treated daily with two dry powder inhalations of 400 micrograms BDP in combination with a bronchodilator. Compliance with BDP was measured by counting capsules (single-blind) at the end of a 4-month period and through a questionnaire. Counting capsules revealed non-compliance in 46% of the patients. Compliance was not related to age, sex, diagnosis or side-effects of BDP. In chronic bronchitis, but not in asthma, compliance was related to the outcome parameters of steroid treatment (pulmonary symptoms, change in lung function and non-specific bronchial responsiveness). The inhaler technique was judged insufficient in 27% of the patients. This study stresses the importance of regular instruction in inhaler technique and proper information about prophylactic steroid treatment by the general practitioner during the treatment of asthma and chronic bronchitis. PMID- 1505704 TI - A practical intervention programme aimed at decreasing high serum cholesterol levels in primary care. AB - A practical, primary care based intervention programme which aimed to lower serum cholesterol in a large percentage of hypercholesterolaemic subjects in general practice is described. Intervention consisted of a 8-10 minute interview supplying oral and written diet counselling. The programme was tried in a kibbutz (agricultural settlement) with 93 adult members: 89 had their serum cholesterol determined, 35 of whom (39%) were hypercholesterolaemic--19 had borderline high cholesterol (5.2-6.2 mmol/l), 16 had definitely high cholesterol (greater than or equal to 6.2 mmol/l). Repeat blood samples were taken from 33 of the 35 hypercholesterolaemic patients 6-9 months after exposure to the intervention programme. The initial cholesterol level of the hypercholesterolaemic group was 6.31 +/- 0.2 mmol/l (mean +/- SE): at follow up it was 5.3 +/- 0.2 mmol/l (P less than 0.001), a decrease in serum cholesterol (mean 22.2 +/- 2.1%) being seen in 28 of 33 patients (84%). In 19 patients (58%) cholesterol dropped to normal values, and in six additional cases (18%) it fell to borderline values. These data suggest that high cholesterol levels in otherwise normal adults may be reduced with little effort by the primary care physician and nurse. PMID- 1505705 TI - Controlled evaluation of management of schizophrenia in one general practice: a pilot study. AB - The study reports on a controlled evaluation of services offered to patients with a diagnosis of schizophrenia in comparison to diabetic patients and matched attenders with no chronic illness. Data were collected from one inner city London group practice, by a retrospective analysis of patients' notes over a period of 6 years. Although patients with schizophrenia attended significantly more often than other patients, clinical assessments in the surgery were rarely undertaken. Communications with hospital consultant services were rare for both chronic groups of patients but in the case of those with schizophrenia the doctor received on average only one letter every 2 years. The findings support other recommendations for a more structured approach to the care of schizophrenia in general practice with regular attention to mental state assessment and monitoring of drug treatment. PMID- 1505706 TI - Perceptions of psychological problems in general practice: a comparison of general practitioners and psychiatrists. AB - All general practitioners and psychiatrists working in a single health district were sent a questionnaire on their perceptions of the prevalence of psychological problems among patients consulting in general practice. One hundred and twenty one GPs (75%) and 10 (83%) psychiatrists responded. GPs and psychiatrists agreed that up to 20% of consulting patients were likely to be clinically depressed; they also agreed on the most appropriate management, although GPs tended to be more conservative than psychiatrists would advise on making use of hospital services. GPs, however, believed non-specific psychological problems to be significantly less common than did psychiatrists. This expectation may help explain the reported failure of GPs to diagnose all psychological problems identified by formal psychiatric instruments. PMID- 1505707 TI - Attaching prices to decision making in general practice. AB - This paper is an attempt to evaluate the cost implications of decisions made by general practitioners during consultations. Prices were attached to the cost generating decisions of 85 general practitioners in South East Scotland who participated in a 12-month study of their workload. When the price attached to each referral decision was one out-patient attendance, 56 of the 85 general practitioners' costs per consultation were within 15% of the average cost, and 76 were within 25% of the average. However, when the price attached to referral activity was adjusted upwards (to allow for the inclusion of further hospital care), variations between doctors became more pronounced and the decision to refer replaced prescribing as the most important element of variable cost. No important relationships were discovered which linked cost generating activities with characteristics of the doctor or the practice. Implications for fund-holding are discussed. PMID- 1505708 TI - Principle agendas of doctors and patients in general practice consultations. AB - Seventy-three general practice interviews were analysed according to the method described by Butler et al. Results for the three principal agenda types (physical, emotional and social) are presented in terms of the control exerted by either doctor or patient in determining the content of the interview. Both doctor and patient address physical agendas to a similar high degree. In contrast, patients present emotional agendas to a far greater extent than doctors address these concerns. The findings for social agendas are intermediate between those for physical and those for emotional agendas. It is argued that doctors can facilitate the expression of emotional and social agendas by giving explicit or implicit permission for their presence in the interview. PMID- 1505709 TI - Reasons for encounter and diagnosed health problems: convergence between doctors and patients. AB - This study of 521 encounters in 25 urban general practices in Australia, compares both patient and doctor reported reasons for encounter (RFE) and diagnoses. Although doctors and their patients generally agreed on the overall distribution of RFE and diagnoses that arose, there was disagreement in at least 30% of paired comparisons within individual encounters. There was better agreement for RFE than for diagnoses. This may have been partly due to differences in the classification systems used. However, it suggests that diagnoses recalled by patients at later household interview are at best only a rough approximation of the diagnoses recorded by the doctor. These findings are important both for patient care and for the conduct of general practice morbidity research. PMID- 1505710 TI - Examination and communication: a study of first encounters between patients and physiotherapists. AB - What happens in first encounters between patients and physiotherapists? Videotaped encounters between two patients and their physiotherapists were analysed in depth to try to answer this question. It is advocated that attention must not be restricted to either clinical decision making or communication, but needs to be directed towards the relationship between communication and diagnostic approaches. In other words, in order to understand how a health problem is defined, the complexity and social organization of the process of interaction cannot be ignored. Therapies are chosen and cooperation is built on such socially and professionally constructed basis, and it is suggested that the nature of this construction needs to be grasped. To this end, the author analyses both the therapists' examination and the communication between patient and therapist. Focus is thereby shifted from the 'pure' diagnostic activity to the frame of reference underlying it. The analysis demonstrates differences in the two therapists' practice from the very moment patient and therapist greet one another till they say farewell. The therapists' actions mirror the dissimilar conceptual frameworks underlying their practice, and the therapists' conceptual lenses therefore need to be scrutinized further. PMID- 1505711 TI - Do physicians care about patients with dysphagia? A study on confirming communication. AB - Thirty-nine patients with longstanding oesophageal dysphagia took part in an interview and a questionnaire study to investigate whether they considered themselves met with interest, respect, understanding and knowledge (felt confirmed) when consulting their physician for the first time (mostly general practitioner), whether non-confirmed patients have any distinguishing attributes, and whether confirmation affects the patient's impression of being helped. Twenty five of these considered themselves as non-confirmed. There was no difference between the groups as regards sex, age, education, degree of swallowing difficulties and incidence of chest symptoms other than dysphagia. There was a greater fear of cancer (P less than 0.05) and a stronger indirect aggression (P less than 0.05) among the non-confirmed patients. Patients who felt confirmed reported more often that a correct oesophageal diagnosis had been given (P less than 0.05), felt they had received adequate help (P less than 0.001) and experienced improvement in swallowing difficulties (P less than 0.05). It is concluded that patient attributes seem to slightly influence the patients' possibilities of being confirmed, and that confirmation is of great importance for the patient's feeling of being helped and improved. PMID- 1505712 TI - A negotiation model for the doctor-patient relationship. AB - A model has been developed to help physicians negotiate with patients in more explicit and effective ways. This model provides physician teachers and learners with a framework and a common language to describe the dynamic nature of the doctor-patient negotiation. This framework consists of three dimensions: content, relationship levels, and the problem-solving phases. The constructs of disease, illness, sickness and the patient's context are used to describe the content of negotiation: this is what the doctor and patient are talking about. Autonomy, power, control and responsibility are the constructs that define the relationship levels: autonomism, egalitarianism, parentalism, and autocracy. These levels describe how the doctor and patient relate to one another during their negotiation. The problem-solving phases are relationship building, agenda setting, assessment, problem clarification, management and closure. Teachers and learners can use this model to describe how the doctor and the patient affect the negotiation process, and how the process in turn affects the doctor-patient relationship and medical care. With practice using this model, physicians can increase their repertoire of negotiating strategies that will efficiently enhance doctor-patient collaboration, the problem-solving process and the health of the patient and family. PMID- 1505713 TI - The interrupted consultation. AB - This paper focuses attention, in a modest empirical way, on a hitherto unexplored phenomenon. Widespread in Israel, the interrupted patient-physician consultation may or may not be found extensively elsewhere. It is assumed that interruptions coming from the social environment affect communication and hence diagnosis and therapy, as well as satisfaction of both doctor and patient. Observations were conducted in a random sample of 100 consultations, averaging 9.4 minutes, of four physicians in a neighbourhood health centre in Israel. Interruptions were recorded in 94 cases, with an average of 1.36 interruptions per consultation. Contrary to Israeli myth, most interruptions were not by other patients but by clinic staff. The phenomenon is considered in terms of cultural practice and the consequences of group practice, nurse autonomy and medical student teaching. Further research is proposed to study the extent, sources and consequences of interruptions in family practice and, if warranted, methods of coping. PMID- 1505714 TI - Problems and issues in family medicine psychosocial research. AB - The authors believe that, despite their complexity, psychosocial factors should be included with biological variables in family medicine research. To aid this process, this article reviews some problems and issues in selected areas of psychosocial research relevant to family medicine. Basic background material, dimensions, models, intra-individual, intra-familial physiological mechanisms of transmission, and factors related to stress, support and coping, are discussed. This is followed by methodological issues that include research design, psychometric properties of measures, data collection, quantitative and qualitative methods, family assessment problems and techniques, and analytic procedures. The latter includes scoring problems, global versus specific questions, and statistical analyses issues. Finally, a discussion of biological relationships and potential biological markers for psychosocial processes or variables concludes this review. PMID- 1505716 TI - List of available training programs. PMID- 1505715 TI - Selections from current literature: prevention of stroke in non-rheumatic atrial fibrillation and carotid artery stenosis. PMID- 1505717 TI - In vitro photosensitivity of ecdysteroid synthesis by prothoracic glands of Rhodnius prolixus (hemiptera). AB - The effects of light:dark transitions on in vitro ecdysteroid synthesis by prothoracic glands (PGs) of male fifth instar Rhodnius have been studied. PGs were rendered arrhythmic by prolonged maintenance of the animals in continuous light (LL). PGs were then explanted and ecdysteroid synthesis was measured hourly by radioimmunoassay. PGs were transferred from LL to darkness at various times after explanation and hourly synthesis was measured for several more hours. Transfer of PGs to darkness in vitro invariably elicited a prompt and substantial (up to fivefold) increase in ecdysteroid synthesis. This response was unaffected by the presence of tetrodotoxin in the medium at a concentration that blocks peripheral nervous activity. It is concluded that the PGs are themselves directly photosensitive. In contrast, PGs from animals raised in continuous darkness and incubated in vitro in darkness showed no response when exposed to light. It is inferred that PGs do not respond to maintained states of either light or dark, or to "lights on." Rather, it is argued that transfer from LL to darkness in vitro constitutes a "lights-off" Zeitgeber which is detected by a photosensitive circadian clock in the PGs. This is the first report of photosensitivity in a steroidogenic tissue and provides primary evidence of a photosensitive pacemaker in a nonneural endocrine tissue. PMID- 1505718 TI - An enzyme-linked immunosorbent assay for stanniocalcin, a major hypocalcemic hormone in teleost. AB - An enzyme-linked immunosorbent assay (ELISA) was developed to quantify stanniocalcin (STC) levels in tissue extracts and plasma samples. The detection limit of the competitive ELISA described is 0.2 ng STC per well, allowing detection of 3.7 pmol.liter-1 (assuming a molecular mass of 54,000 Da for native STC). The particular antiserum detects STC in plasma obtained from a variety of freshwater and seawater species. In freshwater post-smolt Salmo salar plasma, STC levels were significantly lower (around 0.74 nmol.liter-1) than those of seawater smolts (around 2.78 nmol.liter-1). Seven days after removal of Stannius corpuscles from freshwater eels a significant hypercalcemia was observed as well as a drop in plasma STC levels (from 2.33 to 0.67 nmol.liter-1). PMID- 1505719 TI - Sexual development and free-running period in quail kept in constant darkness. AB - In Japanese quail (Coturnix coturnix japonica) sexual development may occur in total darkness (DD). Linked to sexual maturation, variations of the rhythm of feeding activity were observed: in DD, the amount of activity increased and the period of the free-running rhythm lengthened. During the first weeks in DD all the quails presented a free-running period less than 24 hr (22.3 +/- 0.5 hr; N = 50). At the end of the experiment, the more a bird was mature, the greater the lengthening of its period. In DD, testosterone implants in castrated male quails can mimic these modifications but we failed to find any correlation between the number of implants (i.e., the level of testosterone) and the extent of the lengthening. PMID- 1505720 TI - Growth hormone binding sites in tilapia (Oreochromis mossambicus) liver. AB - 125I-labeled bovine and tilapia growth hormones were used to assess the presence of growth hormone receptors in membranes prepared from tissues of the tilapia Oreochromis mossambicus. The highest level of specific binding was detected in liver membranes from animals of both sexes and the binding was protein-dependent. Tilapia growth hormone, bovine growth hormone, and ovine prolactin, but not tilapia prolactin, potently inhibited the hepatic binding of 125I-labeled bovine growth hormone. Scatchard analysis of the 125I-labeled bovine growth hormone binding data revealed a Bmax (maximum binding) value of 180 fmol/mg protein and a Kd (dissociation constant) value of 13 nM. Tilapia growth hormone potently inhibited hepatic binding of 125I-labeled tilapia growth hormone. Scatchard analysis revealed a single class of binding sites with Bmax and Kd values of 390 fmol/mg protein and 2.5 nM, respectively. Bovine growth hormone and ovine prolactin were less potent while tilapia prolactin was inactive in inhibiting hepatic 125I-labeled tilapia growth hormone binding. PMID- 1505721 TI - Primary structures of the hypertrehalosemic peptides from corpora cardiaca of the primitive cockroach Polyphaga aegyptiaca. AB - Two hypertrehalosemic neuropeptides from the corpus cardiacum of the cockroach Polyphaga aegyptiaca were isolated by reversed-phase high-performance liquid chromatography, and their primary structures were determined by pulsed-liquid phase sequencing employing Edman chemistry, after enzymically deblocking the N terminal pyroglutamate residue. As neither peptide was cleaved by carboxypeptidase, the C-terminus of each peptide was also blocked. Both peptides were found to be uncharged octapeptides with the sequences: Peptide 1: pGlu-Leu Asn-Phe-Ser-Pro-Asn-Trp-NH2; and peptide 2: pGlu-Ile-Thr-Phe-Thr-Pro-Asn-Trp-NH2. Both peptides are clearly defined as members of the adipokinetic hormone/red pigment-concentrating hormone family of peptides. Whereas peptide 1 is identical in structure to the previously sequenced hypertrehalosemic neuropeptide from tenebrionid beetles (and is therefore designated the acronym Tem-HrTH), peptide 2 is a novel peptide and is designated the acronym Poa-HrTH. Both synthetic peptides caused an increase in the hemolymph carbohydrate concentration in P. aegyptiaca, specifically changing the trehalose concentration. The novel peptide Poa-HrTH was not very potent in elevating blood carbohydrates in the American cockroach. PMID- 1505722 TI - Annual variations in the binding of insulin to hepatic membranes of the frog Rana esculenta. AB - Amphibia undergo regular annual cycles of metabolic activity that are influenced by both exogenous factors and hormones. Insulin binding to crude frog hepatic membranes was studied throughout the year. The general character of insulin binding was similar to that in other vertebrates; the maximum specific binding was achieved after 4 hr at 4 degrees, the optimum pH was 7.8, half-maximal displacement of bound insulin was from 9 x 10(-10) to 1 x 10(-9) M, and insulin analogs competed for the insulin receptor in line with their relative biological potencies. A biphasic Scatchard plot and negative cooperativity of the receptor were also observed in frog liver membranes. Affinity constants from Scatchard plots revealed high and low affinity binding sites which were unchanged during the year. The seasonal cycle, however, markedly affected the binding capacity for both sites. Maximum binding occurred in May-June and the minimum in November December for both classes of receptors. Binding capacities ranged from 1.71 to 11.33 fmol/mg protein for the high affinity sites and from 432 to 3171 fmol/mg protein for the low affinity sites. It is concluded that annual cycles of insulin binding reflect modulation of receptor number rather than receptor affinity. PMID- 1505723 TI - Thyroid and adrenal function in the ring dove (Streptopelia risoria) during food deprivation and a breeding cycle. AB - The concentration of plasma triiodothyronine (T3), thyroxine (T4), corticosterone, and glucose as well as body weight and food intake were measured in pairs of ring doves throughout a breeding cycle and during food deprivation. During courtship and incubation the levels of plasma T4 were significantly higher in males than in females. A transitory decrease in food intake in both sexes was measured at the onset of incubation but was not associated with a change in body weight or in levels of plasma thyroid hormones. After the eggs had hatched, food intake increased but was associated with a reduction in body weight and concentrations of plasma T3 and T4, although plasma corticosterone and glucose both increased. Food deprivation for 48 hr resulted in a significant fall in the concentration of plasma T3 and an increase in plasma corticosterone. These changes suggest that all the food was not being digested by the adult birds during brooding but was almost exclusively regurgitated to feed the squabs. PMID- 1505724 TI - Influence of dihydrotestosterone on sex determination in channel catfish and blue catfish: period of developmental sensitivity. AB - Treatment of channel catfish with 0.2, 20, or 200 mg/liter of dihydrotestosterone (DHT) in the water during the egg stage or during egg and sac-fry stages did not alter the expected 1:1 sex ratio of the progeny. Feeding DHT at 200 mg/kg of feed for the first 21 days after yolk sac absorption resulted in 80% females; this proportion was increased by combining feeding with treatment of 200 mg DHT/liter in the sac-fry stage (90%) or in the egg and sac-fry stage (97%). In contrast, treatment of blue catfish sac-fry with 200 mg DHT/liter, with or without the combination of feeding DHT at 200 mg/kg food, resulted in 100% female populations. Neither clomiphene citrate, an estrogen-receptor blocking agent, nor clofibrate, an inhibitor of hepatic synthesis of cholesterol, affected the sex ratio of channel catfish, and neither of these compounds altered the feminizing effect of 200 mg DHT/kg when fed in combination with DHT. The nonaromatizable androgen DHT is not as effective as many other androgens in producing paradoxical female populations of channel catfish. However, feminization of blue catfish by treatment of sac-fry indicates that this species is more susceptible to hormonal manipulation and that the period of sex determination may occur earlier in development than in channel catfish. PMID- 1505725 TI - Acid-base-electrolyte balance responses of Bufo marinus to aminoglutethimide, corticosterone, and aldosterone during hypercapnia. AB - Experiments were conducted to test the hypothesis that one or more interrenal steroids are active in regulatory responses to respiratory acidosis in the toad, Bufo marinus. Toads were divided into four experimental groups. The first group received sham injections. The second group received 1-3 mg of aminoglutethimide (AG) every 8 hr. AG inhibits the conversion of cholesterol to pregnenolone, thus inhibiting all steroid hormone synthesis. The third group received AG + 5 micrograms of aldosterone on the same schedule. The fourth group received AG + 25 micrograms of corticosterone on the same schedule as the other groups. All four groups were subjected to hypercapnia using 5% CO2 to induce a respiratory acidosis. The sham-operated animals displayed the normal compensatory pattern of producing a metabolic alkalosis (elevated plasma HCO3-) after 24 hr. AG-treated toads failed to elevate plasma HCO3-. Administration of interrenal steroids produced compensation in varying degrees. Aldosterone produced a small compensation while corticosterone produced a compensation similar to that seen in sham-operated animals. Analysis of steroid titers in toad plasma during hypercapnia showed that Bufo marinus does not elevate aldosterone during respiratory acidosis, but that corticosterone is elevated. AG blocked the corticosterone elevation, however. AG also produced a hyponatremia that was corrected with aldosterone or corticosterone. Normocapnic controls showed that AG does not produce deleterious effects on pH or blood gases in toads in the absence of a respiratory acidosis. We conclude that corticosterone is important in acid base regulatory responses to respiratory acidosis in this amphibian. PMID- 1505726 TI - Duodenal acidification and intra-arterial injection of CCK8 increase gallbladder motility in the rainbow trout, Oncorhynchus mykiss. AB - A sensitive method for in vivo measurement of intra-gallbladder pressure in free swimming rainbow trout (Oncorhynchus mykiss) is described. The method gives information on changes in gallbladder pressure after either instillation of liquids into the duodenum or infusion/injection of agents into the circulatory system. Blood samples can also be taken. Duodenal acidification is a potent initiating factor for gallbladder motility in the rainbow trout. Intra-arterially injected sulfated octapeptide of cholecystokinin is also a potent excitatory agent for activating the gallbladder. Acidification of the upper intestine causes release of cholecystokinin, which affects gallbladder motility in trout as in mammals. PMID- 1505727 TI - Effects of photoperiod and temperature on rhythmic melatonin secretion from the pineal organ of the white sucker (Catostomus commersoni) in vitro. AB - The secretion rate of melatonin from cultured pineal organs of the white sucker was examined for several days under either a 12:12-hr light:dark (LD) cycle or continuous darkness (DD) at either 10 degrees or 20 degrees. The incubation medium was changed at 3-hr intervals and secreted melatonin was measured by RIA. Under a 12:12-hr LD cycle (0800 light on, 2000 light off) melatonin secretion was suppressed during the day and highly active at night, with larger amplitudes at 20 than at 10 degrees. In DD at 10 degrees no circadian rhythmicity in secretion was found in October or January, whereas at 20 degrees a circadian-like pattern was detected in pineals which were derived from animals reared at either 10 degrees or 20 degrees for 1 week prior to the experiment in October or January. The pineals in the DD experiment still responded to an additional 24-hr LD cycle at both temperatures even after 6 or more days. These results clearly reveal the influence of photoperiod and temperature on melatonin secretion of organ-cultured pineal glands. The existence of a circadian oscillator for melatonin secretion in the pineal gland of the white sucker is suggested. PMID- 1505728 TI - Amplexus induces surge of luteinizing hormone in male toads, Bufo japonicus. AB - At mating time in the wild, male toads (Bufo japonicus) exhibit a surge in circulating luteinizing hormone (LH) that is thought to result in spermiation. Experiments were performed to identify proximate control of this gonadotropin surge. Male toads migrating to a breeding pond were captured and put in plastic containers either with equal numbers of females or without females. All the males placed with the females clasped them in amplexus that lasted for about 12 hr. During this period, plasma LH and follicle-stimulating hormone levels increased progressively to about 25 and 2 times the initial levels, respectively, and then returned to the initial levels. No significant increases in plasma gonadotropin levels were observed in the males kept without females. These results suggest that the amplexus directly induced the LH surge, but do not preclude control by pheromonal or visual stimuli. To isolate effects of these factors, solitary male toads were kept with dummies of the female. The dummy was a block of "konnyaku," Japanese food whose component is mannan extracted from the root of a plant. Konnyaku is highly elastic, white in color, and virtually odorless. Thus, these dummies felt, but did not look or smell, realistic. All the males clasped their dummy and formed amplexus for 12 hr or more; an LH surge indistinguishable from that with the females was observed. It is concluded that the amplexus itself is the stimulus that induces the LH surge, and subsequent spermiation, in male toads. A strongly male-biased sex ratio, combined with a need to time spermiation precisely with actual mating, may have resulted in the evolution of this neuroendocrine reflex in male Bufo. PMID- 1505729 TI - Thyroid hormone receptor induction by triiodothyronine in tadpole erythrocytes in vivo and in vitro and the effect of cycloheximide and actinomycin-D. AB - Tadpole erythrocyte nuclei contain specific T3 binding sites which increase in number during spontaneous or T3-induced metamorphosis. In the present studies the increase in the number of T3 binding sites after a T3 injections appeared to be completely prevented by cycloheximide and actinomycin D, inhibitors of protein synthesis and RNA synthesis, respectively. However, in some experiments the effect was not statistically significant. The increase in sites was prevented only if the inhibitors were administered at 0 or 24 hr after T3 injection, but not at 48 or 72 hr after T3. When tadpole erythrocytes were incubated with T3 in vitro in M199 culture medium, the number of nuclear T3 binding sites increased within 48 hr. This increase was highly sensitive to inhibition by cycloheximide (maximal at 1 x 10(-6) M) or actinomycin D (maximal at 0.02 micrograms/ml). These inhibitor concentrations only slightly reduced the incorporation of labeled precursors. The T3 concentration required to induce a half-maximal increase in binding sites in vitro was about the same as the T3 concentration at which half the binding sites were occupied. The T3 binding sites had a high affinity for thyroid hormone analogs which stimulate metamorphosis. These results support the designation of the T3 binding sites as T3 receptors. They show that the tadpole erythrocytes respond to T3 with an increase in the number of T3 binding sites without the involvement of other tissues. It is proposed that this is a receptor induction involving synthesis of RNA and protein. PMID- 1505730 TI - Interactions between progesterone and androgens in the stimulation of sex behaviors in male little striped whiptail lizards, Cnemidophorus inornatus. AB - Progesterone is believed to have a suppressive or inhibitory role in regulating androgen-dependent sex behaviors in male mammals and birds. Previous studies in this laboratory have revealed that in the little striped whiptail lizard (Cnemidophorus inornatus), progesterone (P) can stimulate sex behavior in a proportion of the males. The present study sought to determine (i) interactions between androgens and P in activating sex behaviors, and (ii) the overlap in behavioral sensitivities to androgens and P in male C. inornatus. With an increasing length of castration the behavioral sensitivity of males to exogenous P was reduced. However, priming of castrated males with subthreshold doses of exogenous dihydrotestosterone (DHT) greatly facilitated subsequent behavioral responses to exogenous P. Progesterone treatments of castrated males were more effective at reinstating sex behaviors in males that exhibited high-intensity sex behaviors prior to castration compared to males that exhibited low-intensity sex behaviors. Finally, exogenous DHT is more effective at reinstating sex behaviors in P-sensitive males than in P-insensitive males. These data are discussed in light of possible mechanisms underlying the unusual behavioral effects of P in the Cnemidophorus model system. PMID- 1505731 TI - Ultrastructural investigation of the corpora atretica of the electric ray, Torpedo marmorata. AB - Follicular atresia was studied in the ovary of the electric ray, Torpedo marmorata, by light and electron microscopy. The course of atresia may be divided into four stages. The first two comprise the dissolution of the oocyte and its phagocytosis by the small cells of the granulosa epithelium. The third stage consists of the transformation of the granulosa epithelium into an active glandular structure and is accompanied by the development of a smooth endoplasmic reticulum. The fourth stage is marked by sclerosis and pigmentary degeneration of the atretic follicle. Together these observations suggest an endocrine steroidogenic role for the corpora atretica (preovulatory corpora lutea) in T. marmorata. PMID- 1505732 TI - Immunohistochemical demonstration of the presence and localization of diverse molecular forms of gonadotropin-releasing hormone in the lizard (Podarcis s. sicula) brain. AB - The immunohistochemical presence and the distribution pattern of four different molecular forms of gonadotropin-releasing hormone (GnRH) were investigated in the brain of both sexes of the lizard, Podarcis s. sicula. Animals used in this study were collected in November and April, representing two different periods of the reproductive cycle. The antisera used were those raised against synthetic mammalian GnRH, chicken GnRH-I and II, and salmon GnRH. Strong immunoreaction was obtained for salmon, chicken-I, and chicken-II GnRHs, whereas a very weak reaction was seen for the mammalian form of GnRH. The distribution of immunoreactive-GnRH perikarya and fibers did not vary with the sex, the reproductive condition of the animals, or the antiserum used. Also, the intensity of immunoreaction with any one antiserum was quite similar in both periods of the year and in all brains examined. The immunoreactive perikarya was seen as two distinct groups, one in the mesencephalon and the other in the infundibulum. Immunoreactive fiber endings were seen in the telencephalon, the optic tectum, the anterior preoptic area, the median eminence, the central grey matter, the rhombencephalon, and the cerebellum. No immunoreactive perikarya were seen in the telencephalon or the anterior preoptic area. PMID- 1505733 TI - Effects of growth hormones on bone formation and resorption in rainbow trout (Oncorhynchus mykiss), as examined by histomorphometry of the pharyngeal bone. AB - Effects of salmon and eel growth hormones (GHs) on bone metabolism in rainbow trout (Oncorhynchus mykiss) were studied using histomorphometry of their pharyngeal bones. When salmon GH (sGH) was injected intraperitoneally at a dose of 0.01 or 0.1 microgram/g/week for 10 times into fed trout, body growth in both length and weight was accelerated. Formation and resorption of bone were enhanced only by the higher dose of sGH. When a cholesterol pellet containing recombinant eel GH (reGH-pellet) was implanted subcutaneously into starved trout for 1 week (37 micrograms reGH/18 g fish), formation and resorption of bone increased, although activity of bone formation was low. The results indicate that the GHs increased both formation and resorption of bone, regardless of the nutritional status of the fish. PMID- 1505734 TI - Identification of putative egg-laying hormone containing neuronal systems in gastropod molluscs. AB - Of gastropod molluscs, only in the Aplysiidae and the Lymnaeidae have the genes encoding the respective egg-laying hormones been cloned and the neurons controlling egg laying and egg-laying behavior been identified. Immunocytochemistry, using antibodies raised against alpha-CDCP (one of the neuropeptides encoded on the egg-laying hormone gene of Lymnaea stagnalis), identified neurons in various species of gastropods. In the basommatophoran snail, Biomphalaria glabrata, large and small neurons were observed in areas of the central nervous system similar to where immunoreactive cells exist in L. stagnalis, i.e., in the cerebral and pleural ganglia. In the stylommatophoran snail (Helix aspersa) and the slug (Limax maximus), large immunopositive neurons occur in the visceral and right parietal ganglia. In L. maximus, small immunoreactive neurons were found in the cerebral ganglia while in H. aspersa similar cells were observed intermingled with the large cells in the visceral and right parietal ganglia. Similar to the situation in L. stagnalis, in the female part of the reproductive tract of B. glabrata, L. maximus, and A. californica, but not in H. aspersa, neurons and/or fiber tracts are present. The results indicate that egg-laying hormone precursor molecules of gastropod molluscs are phylogenetically closely related. The alpha-CDCP antiserum may allow the identification of hitherto unknown egg-laying regulating systems of gastropod molluscs. PMID- 1505735 TI - High-level resistance to ethidium bromide and antiseptics in Staphylococcus aureus. AB - A gene encoding high-level resistance to ethidium bromide (EB) and antiseptics was isolated from a transferable plasmid, pTZ22, in Staphylococcus aureus. DNA sequencing revealed that the plasmid has two copies of the ebr gene that normally mediates low-level resistance to EB and antiseptics. The efflux rate for EB of strains with duplicated ebr genes was twice the rate of strains with a single ebr gene. It was concluded that the duplication of ebr is responsible for the high level resistance to EB and antiseptics. PMID- 1505736 TI - A method of enhancing verocytotoxin production by Escherichia coli. AB - The number of verocytotoxin producing Escherichia coli (VTEC) present in the faeces during an infection may be very low, making their detection difficult. We report a method for enhancing toxin production by VTEC using mitomycin C as an inducing agent with the aim of improving the detection of VTEC. In pure culture, mitomycin C enhanced toxin production up to 100-fold. When applied to mixed faecal culture, toxin could be detected in mitomycin C treated samples when standard cultures were negative and when substantially fewer verocytotoxin producing bacteria were present. Use of this method may aid in the detection of VTEC and is appropriate for use in the routine diagnostic laboratory. PMID- 1505737 TI - Bordetella heat-labile toxin causes release of radioactivity from smooth muscle cells labeled with [14C]arachidonic acid. AB - The effect of Bordetella heat-labile toxin (HLT) on cultured vascular or tracheal smooth cells labeled with [14C]arachidonic acid for 3 h was examined. At 37 degrees C, in the presence of Ca2+, HLT induced the release of radioactive substances from the cells in a dose-dependent manner but HLT had no effect on release of radioactivity from cells at 0 degrees C or in the absence of Ca2+. After cells were exposed to HLT, a 2-h lag period occurred before release of radioactivity was detected. The substances released from cells by HLT were identified as arachidonic acid and phosphatidylcholine. PMID- 1505738 TI - Incorporation of S-[3H]methyl-D-cysteine into the peptidoglycan of ether-treated cells of Escherichia coli. AB - Certain D-amino acids can be incorporated into the murein sacculus of Escherichia coli apparently through a direct transpeptidation reaction independent of the normal biosynthetic pathway. Investigation of this process is important because it could lead to the identification of hitherto unknown enzymes involved in murein metabolism. However, a serious drawback is the lack of an appropriate in vitro assay. We have analysed the suitability of a system based on the incorporation of a radioactive substrate (S-[3H]methyl-D-cysteine) by ether treated cells, a method successfully applied before to the study of murein biosynthesis. The results reported here indicate that ether-treated cells are indeed proficient in the incorporation of D-amino acids, matching closely the properties of the reaction in growing cells. PMID- 1505739 TI - Two variants of transferrable extended-spectrum TEM-beta-lactamase successively isolated from a clinical Escherichia coli isolate. AB - In a leukaemic patient presenting a septicaemia treated with ceftazidime and amikacin, two clinical Escherichia coli isolates distinguished by their level of resistance to oxyimino-beta-lactams were isolated at an interval of 24 h. The isolates were identified by biotyping and esterase electrophoretic typing and the two host strains were shown to be identical. However, each of these strains exhibited a different transferrable extended-spectrum beta-lactamase. These enzymes had different pI values (5.25 and 5.58), but were both blaTEM-1 mutants. The enzyme with pI 5.25 was identical to TEM-101 (TEM-12) (serine 162 substitution). The enzyme with pI 5.58 showed an additional amino acid substitution (lysine residue instead of an arginine at position 237) and was denominated TEM-23. These data indicate that point-mutations can be successively cumulated in vivo by blaTEM mutants, leading to expression of beta-lactamases with increased hydrolysis rates. PMID- 1505740 TI - Phylogenetic analysis of the genera Planococcus, Marinococcus and Sporosarcina and their relationships to members of the genus Bacillus. AB - A phylogenetic analysis based on 16S rRNA was performed on the genera Planococcus, Marinococcus, Sporosarcina and endospore-forming rods. In agreement with earlier 16S rRNA cataloguing data, Planococcus citreus and Sporosarcina ureae clustered with Bacillus pasteurii and other bacilli containing lysine in their cell walls. Sporosarcina halophila was shown to be genetically distinct from S. ureae and formed a loose association with the main Bacillus subtilis grouping. Marinococcus halophilus (formerly Planococcus halophilus) exhibited low levels of relatedness to all reference species examined and formed a distinct line of descent. PMID- 1505741 TI - Polyclonal antibodies against Staphylococcus aureus ATCC 12600 catalase do not recognize any protein in cellular extracts from S. aureus subsp. anaerobius. AB - Rabbits were immunized with electrophoretically pure catalase from Staphylococcus aureus ATCC 12 600. The antiserum was used to study whether S. aureus subsp. anaerobius was able to synthesize the apoprotein of catalase. Proteins were separated on polyacrylamide gels (SDS-PAGE) and transferred to nitrocellulose membranes and were detected by immunoblotting. No protein reacting with the purified immunoglobulins against S. aureus ATCC 12,600 catalase could be detected in crude and partially purified cellular extracts from S. aureus subsp. anaerobius or its aerotolerant mutants. PMID- 1505742 TI - Co-transfer of vancomycin and other resistance genes from Enterococcus faecalis NCTC 12201 to Staphylococcus aureus. AB - Conjugative transfer, in the apparent absence of plasmid DNA, of high-level vancomycin resistance from Enterococcus faecalis NCTC 12201 to Staphylococcus aureus B111 has been demonstrated in vivo and in vitro. Selection of transconjugants on media containing erythromycin or chloramphenicol may result in the transfer of resistance to erythromycin, chloramphenicol, gentamicin, streptomycin and vancomycin though these are capable of separate transfer. Vancomycin resistance has not been transmitted from staphylococcus to staphylococcus though transfer of erythromycin and of chloramphenicol resistance has been achieved. PMID- 1505743 TI - Serious physical illness as a stressor: effects on family use of medical services. AB - The purpose of this study was to investigate the effect of stress on the family due to the hospitalization of a family member for a serious chronic illness. The data were the health insurance claims of 3,591 families obtained from the largest U.S.A. insurer of federal employees. It was hypothesized that the nonhospitalized family members would have a stress-related increase in medical expenses for some period of time after the chronically ill person was hospitalized. Multiple regression analysis with adjustments for a number of covariates found increases in mean medical charges of $326 per person (p less than 0.01) (excluding the hospitalized person) in the 3 years following the hospitalization. This finding lends support to the theory that stress--in this case, hospitalization of one family member--affects the entire family system. No significant differences were found in medical charges between families who did and did not receive mental health treatment following the hospitalization. PMID- 1505744 TI - The development of clinical practice guidelines for the diagnosis and treatment of depression. PMID- 1505745 TI - Epidemiology of depression in primary care. AB - Major depressive disorder has been recently found to be associated with high medical utilization and more functional impairment than most chronic medical illnesses. Major depression is a common illness among persons in the community, in ambulatory medical clinics, and in inpatient medical care. Studies have estimated that major depression occurs in 2%-4% of persons in the community, in 5%-10% of primary care patients, and 10%-14% of medical inpatients. In each setting there are two to three times as many persons with depressive symptoms that fall short of major depression criteria. Recent studies have found that in one-third to one-half of patients with major depression, the symptoms persist over a 6-month to one-year period. The majority of longitudinal studies have determined that severity of initial depressive symptoms and the presence of a comorbid medical illness were predictors of persistence of depression. PMID- 1505746 TI - Screening laboratory evaluation in psychiatric patients: a review. AB - Routine laboratory screening of psychiatric patients is a common clinical practice. Several studies have demonstrated the limited utility and higher cost of ambulatory and preadmission screening in the evaluation of general medical patients. The data concerning the use of such screening profiles in psychiatric patients are reviewed. Widespread use of extensive screening batteries, consisting of complete blood cell count (CBC), complete blood chemistry analysis, erythrocyte sedimentation rate (ESR), urinalysis, B12, folate, electroencephalogram (EEG), electrocardiogram (EKG), and chest x-ray film, is not indicated in the majority of psychiatric patients. Such investigations result in many abnormal findings, most of which are clinically insignificant and do not affect patient management and outcome. Most abnormal results can be predicted by information obtained from a careful history, review of systems, and physical examination. Certain populations appear to benefit from more extensive evaluation, including those older than 65 years of age or of low socioeconomic status, state hospital patients, patients with drug and alcohol histories, and patients with evidence of disorientation, self neglect, or organic mental disorders. The few tests that have merit as broader screening tests in asymptomatic patients include serum glucose, blood urea nitrogen (BUN), creatinine, and urinalysis. Patients on psychotropic medications should be monitored for side effects of that particular therapy. Further prospective data are needed to develop cost-efficient, population-specific diagnostic strategies. PMID- 1505747 TI - The depressed alcoholic. Clinical features and medical management. AB - A relationship between depression and alcoholism has long been postulated. A review of prior research studies reveals that though patients with depression do not appear to develop alcoholism to any great extent, recently detoxified alcoholics have a depressive syndrome about 20% of the time. This cannot be accounted for readily from data on family studies or genetic studies, which generally suggest that alcoholism and depression are two independent illnesses, albeit both quite common. Clinically, depressed alcoholics resemble alcoholics more than they resemble depressives. The clinical course of depression when it coexists with alcoholism is generally benign and self-limited, with most patients becoming euthymic over the course of 2-4 weeks without specific antidepressant treatment. In some depressed alcoholics, however, a more chronic depression persists, and may predict a worse outcome for the alcoholism. Treatment of depression in alcoholics should be initially conservative. Tricyclic and other antidepressants should be used with extreme care as they may potentiate toxic effects of alcohol. PMID- 1505748 TI - The epidemiology and treatment of depression when it coexists with somatoform disorders, somatization, or pain. AB - This article reviews the relationship between depressive disorders and somatoform disorders, somatization, and pain. These disorders and symptoms are clinically interrelated, yet the nature of the interrelation is not well understood. This review of the literature from 1975 through mid-year 1990 addresses the epidemiology and treatment of these conditions and/or symptoms when they occur together. When robust criteria are used to determine which publications are included, only 14 are available that address depressive disorders, somatoform disorders, and somatization. Similarly, there are only 13 that address depressive disorders and pain. Taken together, these studies indicate that 1) in somatization disorder patients, there is a high prevalence of depression; 2) in patients with major depression, there are substantial levels of hypochondriacal and somatizing symptoms; 3) that depression in the face of coexisting somatization disorder can be successfully treated; 4) in chronic pain patients, there is a high prevalence of depressive disorders; 5) in patients with major depression, pain is a frequent complaint; 6) and finally, that pain improves with the treatment of depression. What is most striking from this review, however, is the very limited number of studies that address these important problems. This lack of research-based data calls for new aggressive research efforts in this area. PMID- 1505749 TI - The pathogenesis of Munchausen syndrome. A review and case report. AB - The authors present a case of Munchausen syndrome notable for an extended premorbid length and lack of early identifiable antisocial behavior. The patient's life history has been reconstructed, and an integrated psychobiological evaluation of the patient is given including neuroanatomical, neurohormonal, and neuropsychological assessments. Frontotemporal cerebral atrophy and lack of thyroid-stimulating hormone response to thyroid-releasing hormone infusion were found. Although self-object losses did appear to precipitate the Munchausen syndrome in a step-wise fashion, it appears that central nervous system deterioration might have been related to the development of the disorder. PMID- 1505750 TI - Terminal cardiomyopathy, splitting, and borderline personality organization. AB - A 63-year-old married man with idiopathic terminal cardiomyopathy was admitted to the medical service for treatment of advanced heart failure. A psychiatric consultation was requested to assist the medical treatment team in dealing with the patient's abusive behavior. The case is presented and discussed within the context of understanding the borderline personality in the medical setting. PMID- 1505751 TI - Clozapine for the treatment of levodopa-induced psychosis in Parkinson's disease. PMID- 1505752 TI - Anaphylaxis due to latex allergy. AB - An anaphylactic reaction to latex is reported in two patients. One occurred intraoperatively with exposure to the surgeon's latex gloves and the other during vaginal contact with a latex condom. Radioallergosorbent test (RAST) and scratch test with latex material identified the allergen. With the increasing use of latex gloves and condoms, one should be aware of the possibility of a severe immediate hypersensitivity reaction to latex products. Latex allergy should be considered when evaluating intraoperative and idiopathic anaphylaxis. PMID- 1505753 TI - Prevalence of latex sensitivity in children evaluated for inhalant allergy. AB - We prospectively examined 80 children referred to a university allergy/immunology clinic for evaluation for inhalant allergies to determine the prevalence of latex hypersensitivity in this group. All children were skin tested with a Multi-test device to 35 inhalant allergens and a latex glove extract. Only one child gave a questionable history of latex sensitivity, but her skin test was negative. Three of 44 (6.8%) atopic children had a positive latex skin test (wheal greater than 4 mm); none of the 36 nonatopic children had a positive latex skin test. Two of the three children had a history of two or more surgical procedures but denied any clinical hypersensitivity reactions during surgery. Previous reports have demonstrated a personal history of atopy and of surgical procedures as risk factors for the development of latex hypersensitivity. This study helps verify these risk factors and should increase the awareness of this possible health hazard in this select group of children. PMID- 1505754 TI - Idiopathic anaphylaxis: diagnostic variants and the problem of nonorganic disease. AB - We report on an expanding series of cases of idiopathic anaphylaxis (IA) with development of a classification, therapeutic regimens, and control of disease and induction of remission. Simultaneously, a growing series of cases referred for diagnosis and management of IA do not have IA. These cases, which approximate 10% of our series of IA cases, present serious time-consuming diagnostic problems for physicians. We present a series of nine cases of this type of nonorganic disease and describe the presenting symptoms, failure to document clinical abnormalities, and the lack of a response to a regimen shown to be effective in altering the course of true IA. The classification of IA has been expanded to include IA variants for patients in whom the symptoms complex varies significantly from other types of IA. Diagnostic suggestions and the problems of management are reviewed. PMID- 1505755 TI - A cross-sectional survey of 46 employees exposed to trimellitic anhydride. AB - This is a report of 46 employees exposed to trimellitic anhydride (TMA). The evaluation consisted primarily of periodic serum antibody studies and a questionnaire that identified symptoms compatible with allergic asthma and/or rhinitis, late respiratory systemic syndrome (LRSS), or pulmonary disease anemia (PDA) syndrome. Industrial hygiene data from the plant in 1989 reported exposures that were lower than levels in 1979. Seven employees had positive IgE antibody against trimellityl-human serum albumin (TM-HSA); one had TMA rhinitis, and another possibly had TMA asthma/rhinitis. Fourteen employees had positive IgG antibody against TM-HSA of whom only three had titers high enough to cause disease, and none of them had symptoms compatible with LRSS or PDA. At most, two workers had asthma or rhinitis during the 1990 evaluation. In summary, in this employee population with low level TMA exposure there is a low incidence of immunologically mediated disease due to TMA. PMID- 1505756 TI - Asthma in antiquity: the Ebers Papyrus. PMID- 1505757 TI - Ferdinand von Hebra on Erythema multiforme. PMID- 1505758 TI - Bilateral posterior optic neuropathy after bilateral radical neck dissection and hypotension. AB - A 67-year-old man became totally blind after bilateral neck dissection complicated by postoperative hypotension. Histopathological study revealed extensive bilateral infarction of the orbital portion of the optic nerves. PMID- 1505759 TI - Surgical results and complications of goniosynechialysis. AB - Goniosynechialysis (GSL) was performed in 70 eyes with primary angle-closure glaucoma in which the intraocular pressure (IOP) could not be controlled with laser or surgical iridectomy. Following GSL, the IOP was maintained at below 20 mmHg, with and without eye drops, in 34 (87%) of 39 aphakic eyes and in 13 (42%) of 31 phakic eyes. In 8 of 10 eyes, all of which were phakic and the first GSL procedure was not effective, IOP could be controlled by a second GSL procedure combined with lens extraction. Life-table analysis showed a significant difference between the probable success rate, after 5 years, between the phakic and aphakic groups. Postoperative tonographic C values showed improvement in outflow facility. However, frequently encountered complications were exudation of fibrin and minor hemorrhage. Our results suggest that a combination of GSL and extraction of the lens may be necessary to control refractory angle-closure glaucoma. PMID- 1505760 TI - Treatment of persistent epithelial defects in neurotrophic keratitis with epidermal growth factor: a preliminary open study. AB - We report three patients with persistent epithelial defects in the context of neurotrophic keratopathy that healed while on treatment with topically applied, mouse-derived epidermal growth factor (m-EGF). The clinical course of these patients was striking and suggests that EGF may have a potential role in the treatment of persistent epithelial defects in subjects suffering from neurotrophic keratitis. PMID- 1505761 TI - Unilateral congenital corneal staphyloma with retinal neovascularization. A case report. AB - I present the light microscopic and ultrastructural findings in an unusual case of unilateral congenital corneal staphyloma. The anterior segment exhibited features of extensive Peters' anomaly whereas the posterior segment showed marked preretinal neovascularization and lack of axons as well as outer segments. These retinal changes might be secondary due to raised intraocular pressure and traction phenomena, but the complexity and extent of the described malformation argue against this. PMID- 1505762 TI - Electrophysiological findings in paraneoplastic retinopathy. AB - Paraneoplastic retinopathy is a cancer-related non-metastatic retinopathy mainly associated with lung cancer. We examined two patients with presumed paraneoplastic retinopathy, both ophthalmologically and electrophysiologically. Both patients presented with initial visual complaints of moderate reduction of visual acuity. No specific fundus anomaly was found in the fundus except for a mild attenuation of the retinal arteries. The electroretinogram and pattern reversal visual evoked responses were either markedly reduced in amplitude or non recordable. The electrooculogram recorded in one patient demonstrated a markedly reduced light peak/dark trough ratio. These results indicate the presence of a severe and diffuse bilateral retinal dysfunction, despite the relatively good visual acuities and mild fundus changes. Electrophysiological evaluations play an important role in the diagnosis of paraneoplastic retinopathy. PMID- 1505763 TI - Morphological changes in ocular surface in dry eyes and other disorders by impression cytology. AB - A study was conducted on 107 eyes of 70 patients with dry eye disorders and mechanical and chemical extrinsic alterations and 64 eyes of 32 control subjects in order to describe a possible specific response of the conjunctival and corneal surface. We found the presence of "snakelike" chromatin cells and other nuclear changes, squamous metaplasia, and inflammatory cells in the conjunctiva in all groups. A decrease in goblet cell densities was also found in all groups, except for patients with blepharoconjunctivitis. The corneal cells were slightly larger in patients with keratoconjunctivitis sicca. PMID- 1505764 TI - Whiplash and its effect on the visual system. AB - Whiplash or indirect injuries to the neck as a consequence of motor vehicle collisions are a common occurrence in which the frequency of ocular complications is largely unknown. Ophthalmic and oculomotor function was investigated in a longitudinal study of 39 cases who had their initial ophthalmological assessment within one week of the whiplash injury. Ten of 39 cases had ocular symptoms and signs which developed shortly after the accident. The principal abnormality in 6 of these was decreased convergence and accommodation, superior oblique muscle paresis in 2, decreased stereoacuity in 1 and bilateral vitreous detachments in 1 patient. All but 2 had complete resolution of their symptoms within 9 months. Four other patients were asymptomatic but had ophthalmic signs which resolved within 3 months. Oculomotor abnormalities following whiplash injuries are generally mild, have a good prognosis, and would appear from this study to be commoner than hitherto expected. PMID- 1505765 TI - Conjunctival cytology in asymptomatic wearers of soft contact lenses. AB - Conjunctival epithelium was systematically investigated with impression cytology in clinically asymptomatic wearers of soft contact lenses who had been using their lenses for several years. Severe abnormalities were observed, which had so far only been seen in diseases of the ocular surface mainly in dry eye syndromes. All patients showed evidence of squamous metaplasia with distinctly enlarged, flattened cells without evidence of keratinization. They also showed frequent nuclear abnormalities, primarily a high percentage of snakelike-appearing condensations of nuclear chromatin (snakes). The goblet cell density observed was relatively low. Snakes were for the first time detected outside the known localization (upper bulbar conjunctiva, 12 o'clock position) and could be demonstrated throughout the whole bulbar conjunctival epithelium. It is suggested that the changes observed are due to chronic mechanical irritation by the contact lens, as indicated by their topographical distribution and as proven by their reversibility after omission of contact lens wear. PMID- 1505766 TI - Abnormal sclerocytes in nanophthalmos. AB - Scleral tissue from a nanophthalmic patient was examined morphologically and by a tissue culture method. Collagen in the unusually thickened scleral tissue was arranged in irregularly interlacing bundles. Results of tissue culture studies showed sclerocytes that seemed to secrete many granules that stained positively with Alcian blue and periodic acid-Schiff (PAS). No granules were seen in cells of scleral tissue cultured from two control eyes. These findings may be the result of the modified glycosaminoglycan metabolism, which in turn contributes to the abnormal packing of collagen bundles and thickening of sclera in nanophthalmos. PMID- 1505767 TI - Exuberant epibulbar tumor penetrating into the orbit in xeroderma pigmentosum. AB - The clinical and histopathological findings are described in a 10-year-old girl with xeroderma pigmentosum and multiple ophthalmic complications, including the eyelids, conjunctiva, orbit, cornea and iris; some of these complications took an unusual form. Histological examination following right orbital exenteration revealed an epibulbar squamous cell carcinoma penetrating the orbit and building a noose all around the ocular globe with subsequent strangulation. Moreover, a palpebral squamous cell carcinoma developed independently from the right lower lid and, unconnected with the epibulbar tumor, penetrated to the orbit. PMID- 1505768 TI - Foveal flicker-fusion frequencies: a simple, new apparatus (4F). AB - While spatial resolution may be easily assessed with contrast-sensitivity frequency (CSF) data, determination of foveal flicker-fusion frequency (4F) is a simple method of providing the ophthalmic practitioner with accurate information about temporal resolution. The authors describe a simple apparatus that controls luminance, light intensity, light intervals, stimulus size, homogeneity of background illumination, and binocular gaze, especially when using two wavelengths, allowing an increased number of applications with reliable and comparable results. It may prove to be a useful tool for screening, clinical and subclinical assessment, and for evaluating visual acuity, also during follow-up. PMID- 1505769 TI - Severe visual loss associated with retinal telangiectasis and facioscapulohumeral muscular dystrophy. AB - Facioscapulohumeral (FSH) muscular dystrophy is known to be associated with retinal telangiectasis. However, there are only few reports of severe visual loss due to exudative complications, so the risk to vision has not been established. Because of the possible therapeutic implications, we have described two cases of young girls who developed FSH muscular dystrophy and exudative retinal detachment due to telangiectasis. In the first patient, the severity of the disease precluded visual recovery despite extensive photo- and cryotherapy. In the other, visual acuity in both affected eyes was retained after treatment. Fundus examinations in young children at risk of having the gene for FSH muscular dystrophy may be justified so that retinal vascular disease can be detected before it becomes untreatable. PMID- 1505770 TI - C-myc oncogene expression in ocular melanomas. AB - We have investigated the expression of c-myc in 24 ocular melanomas by immunohistochemistry, using two monoclonal antibodies raised against a mid sequence portion of the c-myc product (6E10) and against the C-terminus (9E10). The results were compared with other putative prognostic factors, including tumour size, cell type, proliferation index (determined by flow cytometry), and ploidy, as well as immunohistochemical staining for HMB-45 and S-100 antigens. Staining, often focal, for c-myc was found in both the nucleus and the cytoplasm of a proportion of the cells in most tumours studied. Total cell staining for myc protein correlated with proliferative index in diploid tumours; seven out of nine aneuploid and mixed aneuploid/diploid cells showed strong staining in at least one cellular compartment. A positive correlation with myc expression was also found for HMB-45 staining, but not for cell type or staining for S-100. The results support the hypothesis that myc protein is involved in cellular proliferation in uveal melanomas and indicate that immunohistochemistry for myc antigen may be a useful prognostic marker in these tumours. PMID- 1505771 TI - Axial myopia in eyes with optic nerve hypoplasia. AB - Given that abnormal visual experience during post natal development interferes with emmetropization, we proposed that eyes with hypoplastic optic nerves were predisposed to the development of refractive errors. Six of 14 patients with unilateral optic nerve hypoplasia and 5 of 22 patients with bilateral involvement had at least 4 D of myopia. Nine of the 11 patients with asymmetric bilateral involvement had relative myopia in the eye with the more abnormal optic nerve; none of the patients with symmetric bilateral involvement had a significant interocular refractive difference. Analysis of axial length measurements obtained in 10 of the 11 patients with high myopia showed a significant increase in total axial length. The presumed normal eye of patients with unilateral involvement was significantly smaller than the mean value for age-adjusted normals. We suspect that visual input to the central nervous system is one of the feedback signals involved in the regulation of ocular growth. PMID- 1505772 TI - Dosing problems in the use of topical ophthalmic drops. AB - The effect of two drops of the same drug, one instilled immediately after the other, was compared to the effect of a single drop in 100 healthy volunteers. The drugs investigated were tropicamide, 0.125%, and phenylephrine, 2.5%. The mydriatic effect of two drops was 30%-35% stronger than the effect achieved by a single drop. PMID- 1505773 TI - Electrophysiological and morphological changes in rabbit retina after exposure to the light of the operating microscope. AB - Healthy adult rabbit eyes were exposed to up to 4 h of continuous illumination with moderate light intensity, as is produced by the lamp of an ophthalmic operating microscope. Electroretinograms were recorded before and after the long period of illumination. The depression of the waves in the electroretinograms observed just following light exposure recovered within 1 h to normal values. Electron microscopy of the retina revealed changes within the cells of the pigment epithelium. These results are discussed in view of their clinical implications in human patients. PMID- 1505774 TI - Regional differences in the distribution of cytoskeletal filaments in the human and bovine ciliary epithelium. AB - The distribution of the cytoskeletal elements cytokeratin 18, vimentin, desmin, glial fibrillary acid protein (GFAP), and actin was investigated in different portions of the ciliary body of human and bovine eyes. Regional differences were found only for vimentin and cytokeratin. In both species, cytokeratin staining was more intense in the pigmented (PE) than in the nonpigmented epithelial (NPE) cells. In contrast, immunostaining for vimentin was more intense in the NPE than in the PE. The most intense immunoreactivity for cytokeratin 18 in the PE and for vimentin in the NPE was observed in the posterior pars plana and the crests of the pars plicata. In the remaining portions of the ciliary body, staining was reduced or absent. Desmin and GFAP were not found in the ciliary epithelial cells, whereas actin filaments occurred in both cell layers in all regions. PMID- 1505775 TI - Histopathologic findings in eyes treated with a ruthenium plaque for uveal melanoma. AB - Fifty-six globes that had to be enucleated following ruthenium plaque therapy were examined histopathologically. These eyes account for 10% of all uveal melanomas treated at the University Eye Clinic Essen up until 1985. All but one revealed at least some supposedly viable tumor cells. The most prominent findings within the tumors were tumor cell necrosis, vacuolization and balloon cell degeneration, vascular obstruction and fibrosis of the tumor stroma with accumulation of pigmented macrophages. Tumor necrosis was complete or nearly complete in five cases. Tumor regression correlated with cell type and pigmentary characteristics of the tumor, with epithelioid and heavily pigmented tumor cells being more radiosensitive. Tumor regression was inhomogeneous, possibly due to polyclonality, with tumor cells of varying radiosensitivity, or due to patchy areas of vascular obliteration. Among other ocular structures, extensive subretinal gliosis, chorioretinal atrophy and scarring of the sclera within the field of radiation were observed. Scleral necrosis was present in only five cases and was limited to areas in which the tumor had infiltrated the deep scleral layers. The findings described were considered to reflect radiation injury rather than spontaneous tumor regression when compared to 70 control eyes that had been enucleated without prior treatment for uveal melanoma. PMID- 1505776 TI - On weighted visual field indices. PMID- 1505777 TI - UV-C irradiation-induced peroxidative degradation of microsomal fatty acids and proteins: protection by an extract of Ginkgo biloba (EGb 761). AB - After exposure of rat liver microsomes to UV-C irradiation, analysis of membrane fatty acids by gas chromatography confirmed that EGb 761, a drug containing a dosed and standardized extract of Ginkgo biloba, provides effective protection against free radical attack in vitro. This analysis, coupled with thiobarbituric acid (TBA) reaction, permitted qualitative and overall quantitative evaluation of radical-induced damage to polyunsaturated fatty acids (PUFA), as well as evidence of the antioxidant properties of the Ginkgo biloba extract. Assay of thiobarbituric acid reactive substances (TBARS) showed a correlation between TBARS concentration and the state of degradation of the polyunsaturated fatty acids. Mannitol (5.5 mM) did not prevent degradation of microsomal PUFA or malondialdehyde (MDA) production, nor did it prevent polymerization of membrane proteins. Low doses of EGb 761 were found to provide efficient protection of membrane PUFA regardless of individual susceptibility to peroxidation. This protection was accompanied by a decrease in the production of TBARS. EGb 761 also protected membrane proteins from the irreversible polymerization induced by these degradation products, but did not appear to prevent thiols oxidation into disulfide bonds. PMID- 1505778 TI - The site of nonenzymic glycation of human extracellular-superoxide dismutase in vitro. AB - The secretory enzyme extracellular-superoxide dismutase (EC-SOD) has affinity for heparin and some other sulfated glycosaminoglycans and is in vivo bound to heparan sulfate proteoglycan. Nonenzymic glycation of EC-SOD, both in vivo and in vitro, is associated with a reduction in heparin affinity, whereas the enzymic activity is not affected. The glycation sites in EC-SOD are further studied in the present article. It is shown that modification of a few of the five lysyl residues of the subunits of the enzyme with trinitrobenzene sulfonic acid nearly abolishes the in vitro glycation susceptibility. From a chymotryptic digest of in vitro glycated EC-SOD, two peptides with affinity for boronate could be isolated. Amino acid sequence analysis showed that both encompassed the carboxyterminal end. epsilon-Glucitol lysine was identified in both peptides at positions 211 and 212. The primary glycation sites in EC-SOD are thus lysine-211 and lysine-212 in the putative heparin-binding domain in the carboxyterminal end. PMID- 1505779 TI - Effects of recombinant human extracellular-superoxide dismutase type C on myocardial infarct size in pigs. AB - The efficacy of human extracellular-superoxide dismutase type C (EC-SOD C) to limit infarct size after ischemia and reperfusion was explored and compared to that of EC-SOD C combined with catalase (CAT) and to that of CAT alone. EC-SOD C binds to heparan sulphate proteoglycan on the cell surfaces. Thirty-two pigs were subjected to 45 min of myocardial ischemia followed by 4 h of reperfusion. Control pigs (group A; n = 8) received 300 mL of saline into the great cardiac vein during a 30-min period started 5 min prior to reperfusion; pigs in group B (EC-SOD C; n = 8) got 16.6 mg of EC-SOD C; pigs in group C (EC-SOD C + CAT; n = 8) got 16.6 mg of EC-SOD C together with 150 mg of CAT. Pigs in group D (CAT; n = 8) received 150 mg of CAT. In groups B, C, and D, the drug was dissolved in saline and infused into the great cardiac. Infarct size expressed as percent of area at risk was smaller in groups B (14.5 +/- 16.7%) and C (40.8 +/- 13.3%) than in groups A (78.8 +/- 8.6%) and D (67.2 +/- 18.6%; p less than .05). Creatine kinase (CK) activity in ischemic myocardium was higher in groups B (1740 +/- 548 U/g) and C (1729 +/- 358 U/g) than in groups A (1184 +/- 237 U/g) and D (1251 +/- 434 U/g; p less than .05). There was an inverse relation (r = -.83) between infarct size and CK content. The EC-SOD C infusions resulted in only minimal increases in plasma SOD activities. In conclusion, the presence of SOD on the cell surfaces is of importance in the prevention of reperfusion injury rather than circulating SOD. PMID- 1505780 TI - Peroxidation of lipid emulsions: a hazard for the premature infant receiving parenteral nutrition? AB - Lipid emulsions for parenteral use are peroxidized during storage, indicating that the amount of the natural vitamin E in the preparations is inadequate. Peroxidation products in the lipid emulsion preparations can induce cell damage in vitro. The parenteral administration of lipid emulsions increases in vivo lipid peroxidation in adult and healthy newborn patients as well as in premature infants, whereas enteral feeding seems to lead to a more balanced accretion of polyunsaturated fatty acids. The use of parenteral lipids has recently been associated with increased morbidity of premature infants. Current opinion favors the view that evolution of the complications is highly influenced by the inferior defense of the premature infants to resist oxidant loads. A novel antioxidant added in the preparations for the intravenous provision of polyunsaturated lipids could be beneficial for such patients. PMID- 1505781 TI - Electronic properties and free radical production by nitrofuran compounds. AB - Substitution of nifurtimox tetrahydrothiazine moiety by triazol-4-yl, benzimidazol-l-yl, pyrazol-l-yl or related aromatic nitrogen heterocycles determines changes in the quantum chemistry descriptors of the molecule, namely, (a) greater negative LUMO energy; (b) lesser electron density on specific atoms, especially on the nitro group atoms, and (c) modification of individual net atomic charges at relevant atoms. These variations correlate with the greater capability of nifurtimox analogues for redox-cycling and oxygen radical production, after one-electron reduction by ascorbate or reduced flavoenzymes. Variation of the nitrofurans electronic structure can also explain the greater activity of nifurtimox analogues as inhibitors of glutathione reductase and Trypanosoma cruzi growth, although other factors, such as molecular hydrophobicity and connectivity may contribute to the latter inhibition. PMID- 1505782 TI - The use of fluorescent probes to assess oxidative processes in isolated-perfused rat heart tissue. AB - The formation of reactive oxygen species (ROS) in intact heart tissue has been assessed by direct ESR measurements, and indirectly by the formation of characteristic tissue products and the protective effects of various antioxidants. The development of lipid soluble esters of compounds which can be trapped intracellularly after hydrolysis, and which fluoresce after oxidation, has provided a new tool to investigate ROS in vitro. The utility of 2',7' dichlorofluorescin diacetate (DCFDA) in isolated-perfused rat heart tissue was investigated in the present study. DCFDA and its deacetylated form were incubated with various levels of hydrogen peroxide or t-butylhydroperoxide (tBOOH). Conversion of the diacetate form to a fluorescent product required 4-5 h with hydrogen peroxide and up to 24 h with tBOOH. In contrast, the deacetylated form fluoresced at 80% of maximum levels 1 h after the addition of 100 mM tBOOH. DCFDA was loaded into heart tissue by infusing for 10 min at a final concentration of 10 microM in Krebs-Henseleit bicarbonate buffer. After a 10 min washout period, analysis of freeze-clamped heart tissue revealed that the trapped material was readily converted to a fluorescent product by tBOOH, indicating hydrolysis had occurred. Fluorescence of material trapped in heart tissue was approximately 24% of the maximum achieved after oxidation with 100 mM tBOOH. This value decreased to 18 and 13% when the loading and washout periods were from 0 to 20 or 10 to 30 min of hypoxia, respectively. Similar results were obtained with the less readily oxidized dicarboxy derivative of DCFDA. Infusion of 500 microM tBOOH increased the oxidation of DCFDA in heart tissue from 24 to 31%.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1505783 TI - Formation of stable free radicals from kampo medicines TJ-9, TJ-15, TJ-23, TJ-96, TJ-114 and their antioxidant effect on low density lipoproteins. AB - The Japanese herbal Kampo medicines TJ-9 (A), TJ-15 (B), TJ-23 (C), TJ-114 (D) and TJ-96 (E) were effective (2-5x less than alpha-tocopherol) in inhibiting a copper-induced peroxidation of low density lipoprotein. Kampo medicines dissolved in n-butanol formed stable free radical(s), detected by EPR spectroscopy as a single asymmetric line with g-value g = 2.005. The radical concentration increased in the order: C less than D approximately A approximately E less than B. When the Kampo medicines were oxidized in n-butanol by excess of PbO2 their radical concentration increased 7-15 fold and was in the order C less than D less than A approximately E much less than B. A relationship between the potency of the medicines to inhibit peroxidation of LDL and their ability to form stable free radicals upon oxidation was observed. The medicine which formed more radicals was more efficient in inhibiting peroxidation of LDL. In order to study whether Kampo medicines can reduce alpha-tocopherol radical, the alpha-tocopherol radical was generated by the reaction of alpha-tocopherol with UV irradiated di tert-butylperoxide and by autooxidation of alpha-tocopherol in n-butanol (25 microliters ml-1) in air. In both systems vitamin-C greater than Kampo B decreased the concentration of the alpha-tocopherol radical and the EPR spectrum of Kampo B stable radical(s) appeared. The effect of other Kampo medicines was not clearly seen since their EPR spectra were superimposed with the spectrum of the alpha-tocopherol radical. The results indicate that Kampo medicines possess electron donor properties and ability to form stable radical(s). The results may contribute to understanding beneficial effects of Kampo medicines in diseases in which free radical damage is suggested. PMID- 1505784 TI - Scavenging of lipid peroxidation products from oxidizing LDL by albumin alters the plasma half-life of a fraction of oxidized LDL particles. AB - We analyse LDL oxidation in vitro in the presence of copper (II) ions and differentiate a lag phase and a rapid peroxidation phase. We demonstrate that a physiological concentration of albumin does not alter the kinetics of the dienes in the oxidizing LDL but reduces the fluorescence of the oxidizing LDL and alters the biological properties of oxidized LDL. We find in rats after intravenous administration of oxidized LDL, that it is rapidly cleared from the circulating blood. The presence of albumin during the peroxidation phase, however, reduces the fraction of oxidized LDL with rapid blood clearance. We propose that some lipid peroxidation products formed in oxidizing LDL are hydrophilic enough to diffuse into the aqueous buffer from where they react either with the epsilon amino-groups of apolipoprotein B or albumin. Effective scavengers for these hydrophilic endproducts of the LDL oxidation pathways such as albumin might reduce modification of the LDL and might be useful to reduce its atherogenicity. PMID- 1505785 TI - Oxidative damage in the red cells of vitamin E-deficient rats. AB - One month-old male Sprague-Dawley rats were maintained on a basal vitamin E deficient diet supplemented with either 0 or 50 ppm vitamin E for 5 months. Washed red blood cells were resuspended in phosphate buffered-saline, pH 7.4, that contained 0-50 mM glucose and 0-20 mM ethylenediamine tetraacetic acid (EDTA), and were incubated at 37 degrees C for up to 22 h. Contrary to expectations, glucose in the incubation medium accelerated, rather than retarded, the rates of hemolysis, lipid peroxidation and methemoglobin formation in the vitamin E-deficient cells. EDTA, on the other hand, partially inhibited the extent of oxidative damage. Vitamin E-supplemented cells were resistant to oxidative damage in the presence or absence of glucose and/or EDTA. The levels of reduced glutathione (GSH) and activity of catalase were decreased faster in the vitamin E-deficient cells than the supplemented cells, and the rates of their decline were slowed down by either glucose or EDTA. The activities of GSH peroxidase and superoxide dismutase were not significantly altered in the red cells of either group during incubation. The results obtained suggest that reactive oxygen species and reduced metal ions play important roles in initiating oxidative damage to the red cells of vitamin E-deficient rats. However, the agent responsible for initiating the hemolytic event has yet to be established. PMID- 1505786 TI - DNA base damage in chromatin of gamma-irradiated cultured human cells. AB - We report on the chemical characterization of DNA base damage in chromatin of gamma-irradiated cultured human cells. Chromatin was isolated from unirradiated and irradiated cells and analyzed by gas chromatography/mass spectrometry with selected-ion monitoring after acidic hydrolysis of chromatin and trimethylsilylation of hydrolysates. Prior to analysis of chromatin samples, experimental conditions for acidic hydrolysis were optimized by determining the relative molar response factors of modified bases under non-acidic and acidic conditions, and their release from DNA under various acidic conditions. A number of modified bases in chromatin isolated from irradiated cells were identified and quantitated. These were 5-hydroxy-5-methylhydantoin, 5-hydroxyhydantoin, 5 (hydroxymethyl)uracil, cytosine glycol, thymine glycol, 5,6-dihydroxycytosine, 4,6-diamino-5-formamidopyrimidine, 8-hydroxyadenine, 2-hydroxyadenine, 2,6 diamino-4-hydroxy-5-formamidopyrimidine, and 8-hydroxyguanine. Radiation doses ranging from 42 to 420 Gy (J.kg-1) were used. Background levels of all modified bases were observed in chromatin isolated from unirradiated cells. The radiation yields of a number of modified bases were increased significantly over their background levels at a dose as low as 42 Gy. In most cases, linear dose-yield relationships were obtained up to approximately 200 Gy. At radiation doses higher than 420 Gy, no additional increase in the yields of modified bases was observed. The yields of guanine-derived bases amounted to approximately 45% of the total net yield of modified bases measured, followed by almost equal yields of adenine , cytosine- and thymine-derived bases. Modified bases identified were typical products of hydroxyl radical attack on DNA bases, indicating the involvement of hydroxyl radical, although their induction in part by the direct effect of ionizing radiation through ionization of DNA bases cannot be excluded. The yields of modified bases were lower than those previously measured after gamma irradiation of fully expanded chromatin in aqueous buffer solutions. PMID- 1505787 TI - Limited protection against iron-induced lipid peroxidation by cord blood plasma. AB - The ability of plasma from newborn babies (cord blood) and adults to inhibit iron induced lipid peroxidation was compared. The caeruloplasmin and transferrin concentrations, and latent iron-binding capacity were lower in the babies (p less than 0.001). The plasma of many of the babies had no latent iron-binding capacity and contained non-protein-bound iron (measured by the bleomycin assay). The in vitro ability of plasma to inhibit iron-induced liposome peroxidation by either ferroxidase antioxidant activity (caeruloplasmin) or iron-binding antioxidant activity (transferrin) was measured. The antioxidant activity in both assays was decreased in the babies (p less than 0.001). The percentage inhibition of peroxidation in the iron-binding antioxidant assay correlated positively with the latent iron-binding capacity (p less than 0.001) and negatively with the presence of bleomycin-detectable iron (p less than 0.02) in the babies. This assay produced stimulation of peroxidation in 42% of the babies but none of the adults. The diminished capacity of cord blood plasma to prevent iron-induced lipid peroxidation may predispose the newborn baby to the toxic effects of oxygen. PMID- 1505788 TI - Development of a simple antioxidant screening assay using human skin fibroblasts. AB - The purpose of this study was to develop a simple antioxidant screening assay for quantifying the protective effects of antioxidant enzymes, inhibitors and scavengers against extracellularly generated oxygen species on human skin fibroblast cytotoxicity. Different in vitro oxidative stresses have been studied: xanthine oxidase-hypoxanthine, flavin mononucleotide-NADH, and hydrogen peroxide. Cytotoxicity and protection were evaluated by two procedures: evaluation of the living cells using a colorimetric method (3-(4,5-dimethylthiazol-2-yl)-2,5 diphenyltetrazolium bromide MTT), and ability of the viable cells to adherate and proliferate. Hypoxanthine-xanthine oxidase and H2O2 induced a dose dependent cytotoxicity only when we considered the delayed toxicity. The influence of the cell density was also investigated. The delayed toxicity was higher when cell density increased. One hundred percent protection against free radical cytotoxicity induced by the three systems were obtained with catalase (500 U/ml). When the oxidative stress used was H2O2 90-96% protection was obtained with deferoxamine an iron chelating agent that prevents iron catalysed radical reactions. Using the colorimetric method no significant protection was obtained when SOD was added before and during the stresses. Using the fibroblasts ability to proliferate SOD (10-150 micrograms/ml) reduced xanthine oxidase (20 U/l) hypoxanthine (0.10-0.30 mM) or H2O2 (1-6 mM) cytotoxicity by 15-20%. SOD did not act as antioxidant when the applied stress was mediated by flavin. In this study we showed a paradoxical effect and the cytotoxicity of flavin-NADH system increased when we added SOD to the cell medium. This simple and reliable antioxidant screening assay required no costly or radioactive equipment. PMID- 1505789 TI - Thiol compounds as protective agents in erythrocytes under oxidative stress. AB - The potential for the thiol-containing drugs, N-acetyl cysteine and N mercaptopropionyl glycine, to act as antioxidants intracellularly has been studied in erythrocytes under oxidative stress. The effects have been compared with that of the glutathione peroxidase inhibitor, mercaptosuccinate. The results show differential responses of sickle and normal erythrocytes to the thiol compounds. N-acetyl cysteine is the more efficacious with no toxic effects in these systems. N-Mercaptopropionyl glycine is not only limited in its ability to demonstrate antioxidant capacity in erythrocytes but also exerts deleterious effects. PMID- 1505790 TI - Ischemia and reperfusion: effect of fructose-1,6-bisphosphate. AB - Several lines of evidence indicating a close relationship among ischemia, concentration of high-energy metabolites and onset of the "oxygen paradox" in reperfused tissues have been published. In this framework, we have recently studied the effects of exogenous fructose-1,6-bisphosphate on energy metabolism and on oxygen free radical damages of isolated rat heart subjected to anoxia and reoxygenation. In comparison with control groups, hearts perfused in the presence of 5 mM fructose-1,6-bisphosphate throughout the different perfusion conditions showed higher concentrations of energy metabolites at the end of anoxia, most of which were normalized after reperfusion. Furthermore, in comparison with control hearts, a reduction of tissue malondialdehyde and of lactate dehydrogenase release in the perfusate was observed in fructose-1,6-bisphosphate-perfused hearts. In this article we review most of the available data concerning the ability of fructose-1,6-bisphosphate to protect from ischemia and reperfusion damage outlining those recent findings which contributed both to clarify the pharmacological profile of the drug and to give an insight in its probable mechanism of action. PMID- 1505791 TI - [Obstetrics and brain damage in early childhood]. PMID- 1505792 TI - [The low-birth-weight and premature infant. Ethical aspects from the viewpoint of the obstetrician]. PMID- 1505793 TI - [Neurologic disorders of the fetus]. PMID- 1505794 TI - [Delivery in intrauterine growth retardation and prematurity]. PMID- 1505795 TI - [Intensive monitoring of pregnant diabetic patients]. PMID- 1505796 TI - [Ethical aspects of intensive care of premature and newborn infants]. PMID- 1505797 TI - [Current therapy of respiratory distress syndrome in the newborn infant]. PMID- 1505798 TI - [Perinatal brain damage. Conclusions concerning etiology]. PMID- 1505799 TI - [The risk of cerebral hemorrhage in the newborn infant]. PMID- 1505800 TI - [Fetal monitoring in pregnancy and labor. Conclusions concerning causality of early childhood brain damage]. PMID- 1505801 TI - [Legal liability of the obstetrician and damage to the child from the legal viewpoint]. PMID- 1505802 TI - [Diagnosis and therapy of sterility, II. Evaluation and treatment of ovarian insufficiency (endocrine sterility)]. PMID- 1505803 TI - [Intrapartum CTG]. PMID- 1505804 TI - [Is administration of barbiturates in pregnancy for induction of fetal liver maturity in tocolysis of value?]. PMID- 1505805 TI - Effects of exogenous prostacyclin on placental blood flow, placental weight and fetal weight in normotensive and spontaneously hypertensive rats. AB - Recently, prostacyclin (PGI2) has been used for the treatment of preeclampsia. In this study, we investigated the effects of PGI2 on placental blood flow (measured with clearance of hydrogen gas generated by electrolysis) in normotensive Wistar Kyoto rats (WKY) and spontaneously hypertensive rats (SHR). The placental blood flow of PGI2-treated SHR (0.25, 0.5 and 1 mg/kg) was significantly (p less than 0.05) reduced compared with WKY. These data suggest that PGI2 has a certain reducing effect on placental blood flow in SHR; on the other hand, in WKY, it has an increasing effect depending on the dose. PMID- 1505806 TI - The decidua of early human pregnancy: immunohistochemistry and function of immunocompetent cells. AB - Like the endometrial stroma, the decidua contains lymphoreticular cells, and these are probably involved in immunological interactions between the conceptus and the mother. Lymphoreticular cells in decidual tissue obtained from 12 patients undergoing therapeutic abortion of an intact pregnancy at 6-10 weeks' gestation were investigated in this study. Immunophenotyping with a broad panel of monoclonal antibodies revealed various subpopulations of lymphoreticular cells. Macrophages (Ki-M6+, Ki-M7+, Ki-M8+, KP1+, MAC 387+ and Ki-M1P+) represented the largest fraction of intradecidual lymphoreticular cells. CD3+ and CD8+ lymphocytes were found in moderate numbers and CD4+ cells in small numbers. The majority of the intradecidual lymphoid cells exhibited an unusual phenotype [CD7+, CD2+, CD56+, triple negative (CD3-, CD4-, CD8)]. The distribution of these unusual lymphocytes mirrored that of the so-called endometrial stromal granulocytes. A few of these stromal granulocytes reacted with the macrophage associated antibody KP1, but not with Ki-M1P, another macrophage marker. This was confirmed by immuno-electron microscopy. The finding that intradecidual CD3+ lymphocytes express neither the alpha/beta nor the gamma/delta heterodimer of the T cell antigen receptor was unexpected. However, these cells did express the alpha/beta heterodimer after in vitro culture with PHA-P and recombinant exogenous interleukin-2. No stimulated T lymphocytes expressing activation antigens could be detected. B lymphocytes, T and B immune accessory cells and CD15+ granulocytes were found only in small numbers or were absent. Amongst cells expressing NK cell markers, CD57+ and CD16+ cells were found in small to moderate numbers, while CD56+ cells were detected in large numbers.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1505807 TI - Heparin neutralization by an extract of the human placenta: measurements and the concept of placental barrier to heparin. AB - A soluble extract from human placenta was found to neutralize heparin in a factor Xa-dependent heparin assay system. In comparison with serum the antiheparin activity of placenta tissue is 10 times higher (extract from 1 g of placenta neutralizes 8.94 +/- 3.31 IU of heparin; 1 ml of serum approximately 1 IU). The substance neutralizing heparin has not been identified, but it has been found that it is nondialyzable, is not adsorbed on heparin-Sepharose, and does not act progressively. It was suggested that the substance(s) responsible for the antiheparin effect in vitro might contribute to the failure of heparin to penetrate the placenta in vivo (placental barrier to heparin). PMID- 1505808 TI - Action of alpha-methyldopa on human umbilical circulation in vitro. AB - To determine the possible effects of alpha-methyldopa on the motility of human umbilical artery, a total of 53 arterial segments were perfused with different concentrations of the drug as follows: 38 segments with 125, 250 and 500 ng/ml of the drug, 9 segments with 500 ng/ml alpha-methyldopa in combination with 10(-7) M yohimbine, and 6 segments with 10(-7) M yohimbine alone. alpha-Methyldopa had a vasoconstrictor effect at all doses employed, with a clear dose-effect correlation (p less than 0.01). The vasoconstrictor effect of 500 ng/ml alpha methyldopa was fully inhibited in the presence of 10(-7) M yohimbine. These results suggest that alpha 2-adrenergic receptors are present in the umbilical circulation and that alpha-methyldopa may play a role in the control of this circulation. PMID- 1505809 TI - Differential diagnosis of early human pregnancies: impact of different diagnostic measures. AB - A total of 261 women in early pregnancy, either with mild symptoms of ectopic pregnancy (EP) or being at an increased risk for this condition, were included in a longitudinal study. The effectiveness of different diagnostic measures in obtaining correct final diagnoses was analyzed. In addition to clinical findings and symptoms, the use of serum human chorionic gonadotropin, serum progesterone, endovaginal sonography and a risk score for EP were all proven to be valuable in distinguishing normal intrauterine pregnancies from pathological pregnancies. PMID- 1505810 TI - Post-partum contraceptive preference in high-risk parturients in Maputo. AB - A total of 171 consecutive high-risk parturients in Maputo Central Hospital were studied regarding post-partum contraceptive choice in order to plan a new post natal clinic approach in maternal health care. It was found that contraceptive interest was much less in women with experience of child loss than in women with all children surviving (p less than 0.005). The findings were useful in planning various measures to meet the documented demand for available methods under adverse circumstances of scarce manpower and material resources. PMID- 1505811 TI - Endogenous estradiol and progesterone concentrations in smokers on oral contraceptives. AB - The simultaneous effects of cigarette smoking and oral contraceptives on serum estradiol and progesterone levels were investigated in 114 premenopausal women. Serum 17 beta-estradiol and progesterone levels were measured by radioimmunoassay. In smokers, estradiol and progesterone levels were significantly lower (p less than 0.025). In smokers using oral contraceptives, estradiol and progesterone levels were the lowest (p less than 0.001 and p less than 0.01, respectively). The findings suggest that smoking and oral contraceptives independently lower serum estradiol and progesterone concentrations in premenopausal women and that the effects may be additive. PMID- 1505812 TI - Evaluation of the clinical method of measuring cervical dilatation after treatment of the cervix prior to first trimester abortion. AB - A comparison of the subjectively measured cervical dilatation and the dilatation measured objectively with a force-sensing instrument connected to metal dilators was made in two studies of cervical treatment prior to first trimester abortion. It was concluded that the subjective method is a sensitive and accurate method of measuring cervical dilatation but does not allow for comparison between different studies where an objective method of measurement should be used. PMID- 1505813 TI - Evaluation of bone metabolic markers as indicators of osteopenia in climacteric women. AB - Lumbar bone mass (LBM) determination by quantitative computerized tomography in pre-, peri- and postmenopausal women was utilized to identify subjects at risk to develop osteoporosis. The results were related to determinations of bone metabolic markers (serum osteocalcin and urinary calcium excretion). Osteocalcin was the only metabolic marker which underwent significative changes. However, we found very poor correlations between LBM and metabolic markers and it is concluded that bone mass determination remains the method of choice to select women for preventive therapy. PMID- 1505814 TI - Delay in the diagnosis of rupture of the uterus due to epidural anesthesia in labor. AB - A case report of uterine rupture in labor with epidural anesthesia is presented. The woman had good analgesia on the left side, but complained of severe labor pais on her right side. Uterine rupture occurred which was manifested by sudden vaginal bleeding, fainting, low blood pressure and fetal distress. She did not feel any pains typical of uterine rupture. Rupture of the left uterine wall, with a large hematoma in the left parametrium was seen at surgery. It seems the unilateral anesthesia of the left side concealed the early signs of rupture. PMID- 1505815 TI - Maternal hemorrhagic complications following prophylactic low-dose aspirin and dipyridamole therapy. AB - A case is reported of a severe postpartum maternal hemorrhagic complication, which was related to prophylactic antithrombotic therapy with daily low-dose aspirin (75 mg) combined with dipyridamole (225 mg) for the prevention of preeclampsia. The postpartum course was complicated by recurrent episiotomy site hematomas of nonclotted blood and prolonged bleeding time. Transfusion of platelet concentrates was necessary to control the bleeding. This case report draws attention to maternal hemorrhagic complications which may be associated with prophylactic low-dose aspirin and dipyridamole in pregnancy. PMID- 1505816 TI - Third trimester torsion of persistent ovarian cyst following ovarian hyperstimulation--an unusual cause of preterm labor. AB - Herein, a patient being operated for cesarean section due to preterm labor in the 31st week of a triplet pregnancy induced by gonadotropins is being described. On celiotomy, peritoneal effusion was present secondary to torsion of a 10 x 6 cm right ovarian cyst. This uncommon finding contradicts the common belief that the chances for an ovarian cyst in the overcrowded peritoneal space due to a 40-week size uterus to twist around its pedicle are remote. The possibility that preterm labor was initiated by the torsion is discussed. PMID- 1505817 TI - Independent origin of uterine leiomyomas with karyotypically identical alterations. AB - Cytogenetic investigation of multiple uterine leiomyomas from the same patient revealed karyotypes containing cytogenetically indistinguishable del(7)(q21.2q31.2) in two of the tumors. Since this finding seemed to contradict the conclusion from previous glucose-6-phosphate dehydrogenase studies of multiple uterine leiomyomas in which an independent origin of these tumors was found, we assessed clonal tumor origin by DNA-recombinant X-chromosome inactivation analysis. The two leiomyomas with del(7)(q21.2q31.2) had different inactivated X-chromosomes. This proves that they originated independently and indicates that their cytogenetic similarity was coincidental. PMID- 1505818 TI - [Use of thrombolysis for myocardial infarction in Israel]. AB - Thrombolysis is generally accepted as the initial treatment for acute myocardial infarction. The extent to which this therapy is being implemented in Israel and the reasons for exclusion of cases from thrombolytic therapy were prospectively investigated. 413 consecutive patients with acute myocardial infarction hospitalized during January 1990 in 18 of Israel's 25 coronary care units were studied. Thrombolytic therapy was administered to 145 patients (35%: 38% of the men and 29% of the women; NS). It was used more often in those up to the age of 75 (38%) than in those over (18%, p less than 0.005) and in those with a first or anterior infarction (40% and 48%, respectively) than those with recurrent or inferior infarction (23% and 31%, respectively; p less than 0.005 for both). The 2 most frequent reasons for not using thrombolysis were late arrival in the coronary care unit (33%) and absence of ST elevation on the admission electrocardiogram (28%). Hospital mortality was 6% in the thrombolytic group versus 20% in those ineligible for thrombolysis. The significance of this difference is not clear as there was no randomization to treatment. PMID- 1505819 TI - [Hypertension in the community]. AB - Hypertension is a major risk factor for cerebral and coronary disease and its early detection is very important for the family physician. We checked the implications of a hypertension survey in the community (from the age of 10 years) on the attitude of the primary care team. We found that although the medical team was aware of the significance of early detection and treatment of hypertension, according to the "law of halves" half the hypertensives were in treatment and of them half had normal blood pressure. This fact is probably not related to the quality of medical care. High risk groups identified were hypertensive patients who smoked, Jewish men of western origin, and Jewish women of Asian-African origin (who had a high rate of strokes). These groups were targeted for active intervention by the primary care team. This survey is part of planned community intervention by the primary care team in the field of hypertension. PMID- 1505820 TI - [Treatment of retinal detachment with intraocular expandable gas injection]. AB - The injection of expandable gas into the vitreous is a new method for treating retinal detachment. The injected gas bubble seals the retinal break and allows absorption of subretinal fluid. In 12 patients, in all eyes treated by injection of sulfur hexafluoride, the detached retina became reattached. In 3 eyes (25%) detachment recurred. To achieve attachment again, both vitrectomy and the circling band operation were performed in 2 of them, and only the latter operation in the third. Risk factors for redetachment included detachment of the macula, retinal detachment larger than 5-o'clock-hours, and pseudophakia. Proper selection of patients for gas injection is most important. PMID- 1505821 TI - [Familial breast cancer in Arabs]. AB - 500 surviving Arab cancer patients in follow-up were interviewed with regard to other cases of cancer in their families. Among 73 who had breast cancer, in 15 (20.3%) there was another case of breast cancer among first-degree relatives. The incidence of both primary and familial breast cancer was higher among Christian than among Moslem women. We conclude that Arab women with breast cancer in their families are at high risk for developing breast cancer themselves. PMID- 1505822 TI - [Echinococcosis in pregnancy]. AB - Hydatid disease affects sheep and cattle and is caused by the larval form of Echinococcus granulosus. Affected human beings are only chance intermediate hosts. We present a woman admitted in her 22nd week of pregnancy because of upper abdominal pain and persistent vomiting. The presumptive diagnosis of hydatid cyst of the liver was established by ultrasound, X-ray and CT examinations. At laparotomy a 10 x 7 cm hydatid cyst was removed from the liver. She recovered completely and delivered spontaneously at term. There was no evidence of hydatid disease in the newborn or in the placenta. PMID- 1505824 TI - [Idiopathic scrotal edema]. AB - Idiopathic scrotal edema causes painful enlargement of the scrotum, as does torsion of the testis or of a testicular appendage, or epididymo-orchitis. Unilateral edema of the scrotum develops rapidly, the skin becomes pale pink or red, and there is discomfort rather than acute pain. Careful palpation reveals a nontender testis. The condition is usually self-limited, and resolves completely without treatment in 48 hours. It must be differentiated from testicular torsion, for which urgent surgical treatment is mandatory. PMID- 1505823 TI - [Surgery for complete rectal prolapse in adults]. AB - Surgery for complete rectal prolapse was performed in 17 women and 3 men between November 1986 and April 1991. An abdominal approach with posterior rectopexy was used in 17. The Thiersch procedure of anal narrowing was performed in 3 high risk patients. All recovered without major complications. Urinary tract infection developed in 15% and postoperative fecal impaction in 10%. Anal continence improved in 70% of those previously incontinent. There was no recurrence of complete rectal prolapse during follow-up. All patients rated the operative results as either good or very good. PMID- 1505825 TI - [Significance of mass screening for early detection of cervical cancer in Israel]. PMID- 1505826 TI - [Anesthetic considerations in mast-cell proliferative disease (urticaria pigmentosa and mastocytosis)]. PMID- 1505827 TI - [Colony stimulating factors as a treatment modality for acute radiation syndrome]. PMID- 1505828 TI - [Late neuromuscular deterioration in survivors of poliomyelitis]. PMID- 1505829 TI - [Radial keratotomy for correcting myopia]. PMID- 1505830 TI - [Hereditary disorders of the skeleton of the red cell membrane]. PMID- 1505831 TI - [Emotional stress and sudden death]. PMID- 1505832 TI - [The case against cytological mass screening for cervical cancer in Israel]. PMID- 1505833 TI - [Strategies and challenges in the development of gene therapy]. PMID- 1505834 TI - [Extreme pulmonary hypertension in hypertrophic obstructive cardiomyopathy]. PMID- 1505835 TI - [Surfactant replacement therapy for respiratory distress syndrome: a pilot study]. AB - A pilot study of the effect of exogenous surfactant (ES) on premature infants with respiratory distress syndrome (RDS) is reported. Each of the first 15 infants in this study received 200 mg/kg of natural surfactant (Curosurf) during the first day of life. Controls were 56 infants with RDS seen in the 15 months prior to the study. Within 5 minutes of starting ES, in all infants there was rapid and dramatic improvement in oxygenation and improvement in the average arterial/alveolar ratio of 169%. They had lower oxygen and ventilatory requirements than the control group throughout the first 5 days of life. No treated infant suffered from pulmonary air leak, while in the control group 21% developed pneumothorax and 11% had pulmonary interstitial emphysema. Mortality was 13% in the treated group as compared to 27% in the control group (p less than 0.01). There were no differences between the groups in the incidence of sepsis, patent ductus arteriosus, necrotizing enterocolitis, intraventricular hemorrhage, or bronchopulmonary dysplasia, nor were there side-effects of therapy. Dosage, timing and composition of the ideal surfactant are important questions for future studies. PMID- 1505836 TI - [Diathermy-induced gas explosion in the intestinal tract]. AB - Surgical diathermy is widely used in modern operating rooms, although explosion in the gastrointestinal tract is a known serious complication. We report a case of colonic explosion following use of diathermy. Based on our experience and the available data, it is recommended that in cases of gastrointestinal tract obstruction, poor bowel preparation or following use of oral mannitol for bowel preparation, diathermy should be avoided in opening the gastrointestinal lumen. PMID- 1505837 TI - [Implanted subcutaneous venous catheter for prolonged intravenous treatment]. AB - Subcutaneous venous catheter devices were implanted in 104 patients between January 1989 and June 1991. In 90% the implantation was performed under local anesthesia as an ambulatory procedure. In 85% the catheter was implanted for long term chemotherapy and in 15% for intravenous feeding, antibiotic treatment or dialysis. There were postoperative complications in about 10%, the most frequent being infection of the surgical wound or of the catheter canal. Venous thrombosis, cutaneous necrosis and catheter occlusion were observed in only 5%. The main advantages of the method are its convenience for the patient, ease of installation and low rate of complications. From our experience we conclude that the implanted subcutaneous venous catheter is a simple and effective procedure for prolonged intravenous treatment. PMID- 1505838 TI - [Desmoid tumors]. AB - Desmoid tumors in various anatomic sites were treated in 4 females and 3 males, ranging in age from 16-50 years, during a 6-year period. In 5 the tumor was completely excised with free margins. In the other 2 excision was incomplete and the tumor recurred within a few months. Desmoid tumors have a marked tendency to local recurrence, and therefore should be widely excised. There is no evidence that adjuvant therapy has a place in the management of these tumors. PMID- 1505839 TI - [Repair of esophageal perforation with a diaphragmatic flap]. AB - Perforation of the esophagus is life-threatening and requires prompt diagnosis. Immediate surgery with primary suture of the perforation is the treatment of choice. Any delay in diagnosis or treatment results in a sharp increase in mortality due to the combination of rapid development of necrotizing mediastinitis and inability to close the perforation surgically. To avoid leaks from the anastomosis the suture line can be buttressed with adjacent structures. The fundus of the stomach, parietal pleura and muscular flaps have been used to cover the perforation. We describe 2 patients with perforation of the lower esophagus. Both were operated on within 8 hours, the perforation was closed primarily and a diaphragmatic flap was formed to cover the suture line. There were no postoperative leaks and recovery was uneventful. PMID- 1505840 TI - [Assessing judgment in dementia]. PMID- 1505841 TI - [Urinary diversion in gynecologic oncology]. PMID- 1505842 TI - [Continuous spinal anesthesia]. PMID- 1505844 TI - [Rheumatic fever--an immunogenetic disease]. PMID- 1505843 TI - [Positive end-expiratory pressure and prognosis of the adult respiratory distress syndrome]. PMID- 1505846 TI - [Pathogenetic aspects of sarcoma of blood and lymph vessels]. PMID- 1505845 TI - [Hypothalamic-pituitary-adrenal dysfunction in adolescent girls with anorexia nervosa]. PMID- 1505847 TI - [Enteroperitoneal anastomosis for short bowel syndrome]. AB - Creation of neomucosa is one of many experimental surgical techniques tried in order to improve the results of the complicated treatment of short bowel syndrome. The syndrome is associated with severe physical and mental retardation and not infrequently may be fatal. In this experimental study on pigs and rats we successfully enlarged the small bowel surface by growing new mucosa on the parietal peritoneum following enteroperitoneal anastomosis. The technique has 2 more important advantages: fluids and electrolytes are absorbed through the peritoneum and bowel transit time is slowed. PMID- 1505848 TI - [Chemoprevention of neonatal jaundice]. PMID- 1505849 TI - [Passive smoking: clinical aspects and workers' awareness]. AB - Tobacco smoke contains a wide range of toxic vapors and particles which when inhaled are injurious both to the smoker himself (active smoking) and to those around him (passive smoking). It is extremely difficult to define precisely the harmful effects of passive smoking on the individual's health because of problems in quantifying the extent of exposure. A number of epidemiological studies indicate that exposure to passive smoking in public places is circumstantially, but marginally, linked to cardiovascular morbidity and mortality, as well as to pulmonary morbidity. both benign and malignant. Many clinical conditions are further aggravated by exposure to a combination of tobacco smoke and other industrial materials, including cadmium, and radon daughters. Passive smoking during pregnancy constitutes a health hazard for both mother and fetus. Exposure to passive smoking during childhood may predispose to benign and malignant pulmonary morbidity in adulthood. For many the workplace is the main site of exposure. In a pilot study during the past year on 1197 white and blue-collar workers, we found that the proportion of nonsmokers exposed to tobacco smoke at work is very high, almost 80%, and that workers are bothered by it. 2/3 are aware of the serious adverse health effects of tobacco smoke. 98% of the passive smokers and 75% of the active smokers considered legislation to limit smoking in public places justified. PMID- 1505850 TI - [The thymus--30 years afterwards]. PMID- 1505851 TI - [Flat foot--the exact diagnosis]. PMID- 1505852 TI - [Effect of workload on physicians' drug prescribing]. AB - The possible effect of workload on the prescribing of drugs by physicians was studied in 10 primary care pediatricians during a 1-month period. The intraphysician variability revealed a positive correlation (p less than 0.05) between workload and prescription of antibiotics in the case of 2 of the physicians and a negative correlation (p less than 0.05) between workload and prescription of all drug items in another physician. The prescribing of the other 7 was not affected by changes in daily workload. The interphysician variability study revealed a significantly increased rate of prescription of analgesics/antipyretics by physicians with increased monthly workload (r = 0.91, p less than 0.001). These results suggest that although the prescribing habits of a minority of physicians may be affected by their workloads, prescription rates remain stable for the individual physician on most occasions. However, physicians with high workloads tend to prescribe more analgesics/antipyretics than those with low workloads. PMID- 1505853 TI - [Effects of oxiracetam on the decrease in population spikes in hypoxic and low glucose media]. AB - Evoked potentials were recorded in rat cerebral cortical slices. The amplitude of the evoked potential was reduced by perfusion with hypoxic (0-25%) or low glucose (0-5 mM) media in a concentration-dependent manner, and the evoked potentials disappeared under severe conditions (below 15% O2, below 3 mM glucose). We investigated the protective effects of oxiracetam on the decrease in evoked potentials under hypoxic (15% O2) and low glucose (3 mM glucose) conditions. Drugs were perfused from 45 min before hypoxic or low glucose perfusion to the end of the experiment. Oxiracetam (10(-6)-10(-5) M) dose-dependently minimized the amplitude reduction of evoked potentials and prolonged their disappearance time. At a concentration of 10(-5) M, oxiracetam protected against the disappearance of evoked potential in 5 of the 6 samples under hypoxic conditions and in all 6 samples under low glucose conditions. Indeloxazine (5 x 10(-6)-10( 5) M) and bifemelane (5 x 10(-6)-10(-5) M) prevented the reduction of the amplitude of evoked potentials under low glucose conditions. However, these drugs had no effect at a concentration of 10(-6) M. These data indicate that oxiracetam has a protective effect against neuronal dysfunction and that this effect develops at a lower concentration than those of indeloxazine and bifemelane. PMID- 1505854 TI - [Pharmacological effects of Gosha-jinki-gan-ryo extract: effects on experimental diabetes]. AB - Pharmacological effects of Gosha-jinki-gan-ryo extract (KJE) on experimental diabetes induced by cyproheptadine (CPH), aldose reductase activity, and experimental peripheral neuropathy were studied. The effects of KJE were compared with those of Hachimi-jio-gan-ryo extract (HJE). KJE at 417 mg/kg/day (5 times the daily dose in humans) and HJE at 367 mg/kg/day (5 times the daily dose in humans) significantly inhibited the decrease in glucose tolerance by CPH. KJE and HJE inhibited aldose reductase activity, when DL-glyceraldehyde was used as substrate, with IC50 values of 2.68 x 10(-5) g/ml and 4.45 x 10(-5) g/ml, respectively and when D-glucose was used as substrate, with IC50 values of 1.04 x 10(-4) g/ml and 1.55 x 10(-4) g/ml, respectively. KJE at 209 mg/kg/day (2.5 times the daily dose in humans) and HJE at 367 mg/kg/day significantly reduced peripheral neuropathy induced by crushing the sciatic nerve in rats. The potency of these effects of KJE was stronger than that of HJE, when a comparison was made on the basis of the daily dose. PMID- 1505855 TI - [Effects of mosapramine (Y-516), a new dopamine D2 antagonist, on reverse tolerance after repeated administration of methamphetamine by means of the ambulation-increasing effect in mice]. AB - Effects of mosapramine (Y-516), a new dopamine D2 antagonist, on reverse tolerance (sensitization) after repeated administration of methamphetamine (MAP; 2 mg/kg, s.c.) were investigated by means of ambulatory activity in mice; and they were compared with those of clocapramine (CCP), bromperidol (BPD) and chlorpromazine (CPZ). Y-516 (0.3, 1, 3 and 10 mg/kg, p.o.), CCP (3, 10 and 30 mg/kg, p.o.), BPD (0.1, 0.3 and 1 mg/kg, p.o.), CPZ (1, 3 and 10 mg/kg, p.o.) or 0.5% methylcellulose (MC; solvent, p.o.) were given to mice 30 min before MAP administration. The ambulatory activity was measured by tilting-type activity changes for 3 hr after MAP. These treatments were repeated 5 times at 3-4 day intervals. Then MAP alone was challenge-administered to all of these mice 3-4 days after the final administration. Marked reverse tolerance was produced after repeated administration of MC plus MAP. On the other hand, the ambulation increasing effect of MAP was suppressed dose-dependently in groups pretreated with Y-516 or comparison-drugs, although the development of reverse tolerance was not completely inhibited after the repeated administration. In the challenge administration of MAP, the ambulation-increasing effect was dose-dependently suppressed in the Y-516 group or the comparison-drug plus MAP group as compared with that in the MC plus MAP group. PMID- 1505856 TI - [Inhibitory effects of Hachimijiogan on micturition reflex via the locus coeruleus]. AB - Pharmacological studies were undertaken to elucidate the role of Hachimijiogan in the micturition reflex via the locus coeruleus, using alpha-chloralose anesthetized cats. Rhythmic contractions of the urinary bladder induced by continuous infusion of saline into the bladder were dose-dependently inhibited by intravenous injection of Hachimijiogan (10, 30 and 90 mg/kg), as well as flavoxate hydrochloride (1 and 3 mg/kg). In contrast, contraction of the urinary bladder elicited by electrical stimulation of the locus coeruleus was significantly suppressed by intravenous injection of flavoxate, but not affected by that of Hachimijiogan. These results suggest that Hachimijiogan acts on the afferent pathway from the urinary bladder to the locus coeruleus, thereby inhibiting the micturition reflex, while it has no effects on the efferent pathway from the locus coeruleus to the urinary bladder. PMID- 1505857 TI - [Influences of hypercholesterolemia on the vessel function of isolated rat thoracic aorta]. AB - Mature male rats (SD strain, 8-week-old) were fed with a normal diet or a high cholesterol diet (HC: 1.5% cholesterol and 0.5% Na cholate in the normal diet) up to 8 weeks, and we examined how the vascular function level of the isolated thoracic aorta and the histological figures of some tissues including the aorta would change. 1) The contracting reactivity to phenylephrine (Phe, 10 microM) and the relaxing reactivity to acetylcholine (1 microM) measured thereafter remained unchanged during the period of aging and were not influenced by HC-feeding. The addition of L-arginine (Arg, 100 microM) did not affect the results. 2) The ability of the aorta to release NO and to relax, which was evaluated as the extent of the endothelium-dependent potentiation by NG-monomethyl-L-arginine (NMA) of the Phe contraction, did not change by HC-feeding up to 4 weeks, but appears to be attenuated after 8-week feeding. 3) The EC50 of NMA for the potentiation estimated without the addition of Arg remained unchanged, while the one in the presence of Arg gradually increased with aging but not with HC feeding. 4) The histopathological study of the aorta and other tissues failed to detect any notable atherogenic changes in any of the HC-fed groups. The results indicate that under the experimental conditions employed, HC-feeding would not develop any significant atherogenic histopathological changes in the endothelium smooth muscle preparation, but may induce some dysfunction in the NO-release mediated and auto-regulatory function of the vascular tone. PMID- 1505858 TI - Cell growth and alpha-amylase production characteristics of Bacillus subtilis. AB - Growth, differential rate of alpha-amylase synthesis and production characteristics of Bacillus subtilis DP 1 (isolate from starch materials) in comparison with 10 Bacillus strains were examined in batch fermentation. The effect of the carbon and nitrogen source was evaluated with regard to cell growth and enzyme production. The pH optimum of enzyme activity was 6.5 and temperature optimum of 60 degrees C. PMID- 1505859 TI - Immunological quantification of RecA protein in cell extracts of E. coli after exposure to chemical mutagens or UV radiation. AB - Increased synthesis of RecA protein is induced in E. coli cells after their damage, the rate of synthesis being dependent on the extent of DNA alterations. The level of the RecA protein was determined in E. coli cell extracts after damage induced by NQO, MNNG, MMC, NAL or UV radiation, using competitive enzyme linked immunosorbent assay (ELISA). Purified E. coli RecA protein and rabbit monospecific polyclonal antibodies against it were prepared for the quantitative assay. The level of the RecA protein was increased after treatment with all mutagens. Contrary to other induced proteins, the synthesis of the RecA protein increased within 30 min after damage with UV radiation at a relatively slow rate. The ELISA method made it possible to determine 0.5-50 ng of the RecA protein in bacterial extracts. The method can be employed as an auxiliary test for DNA damage determination and also in studied concerning the role of the RecA protein in repair processes. PMID- 1505860 TI - Biological effects of the antibiotic brefeldin A (decumbin, cyanein, ascotoxin, synergisidin): a retrospective. AB - Brefeldin A has been recently characterized to act as an inhibitor of intracellular protein export with profound effects on the structure and function of the Golgi apparatus in animal cells. Manifold activities of the antibiotic (under different names) published in the 1960's and 1970's are reviewed: effects on fungal growth and morphogenesis, inhibition of mitosis in plant cells, cytotoxicity, cancerostatic, antiviral and antinematodal activity and peculiar effects on DNA, RNA and protein synthesis in microbial and animal cells. PMID- 1505861 TI - Effect of growth rate on ethanol tolerance of Saccharomyces cerevisiae. AB - delta 5,7-Sterol-accumulating Saccharomyces cerevisiae cells growing in chemostat at a specific growth rate of 0.075/h exhibited higher ethanol tolerance measured as ethanol-induced death and anaerobic growth inhibition than the cells growing at 0.2/h, the difference being dependent on the carbon-to-nitrogen molar proportion in the medium. The observed difference in sensitivity to ethanol of anaerobic growth between the slowly and rapidly-growing cells was completely reversed as a result of a block in sterol synthesis causing a negligible synthesis of delta 5,7-sterols. Two physiological parameters, budding frequency and membrane composition, evidently affected ethanol tolerance. Differences between the delta 5,7-sterol-synthesizing and deficient strains documented a profound effect of the quality of the sterol present on the physiological state of the cell. PMID- 1505862 TI - Effect of carbon and nitrogen sources on the production of penitrem B by Penicillium aurantiogriseum. AB - Effect of different carbon and nitrogen sources on the production of penitrem B was studied. D-Xylose induced maximum penitrem B production, while melibiose, glycerol, citric acid and succinic acid were poor substrates. Potassium nitrate, L-asparagine, sodium nitrate, glycine, DL-aspartic acid and L-tryptophan supported good production of penitrem B. Conversely zirconyl nitrate, barium nitrate, aluminum nitrate, acetanilide, 4-aminobenzoic acid, 4-nitrobenzoic acid and 4-nitroaniline were toxic and did not even permit the growth of the fungus. PMID- 1505863 TI - Regulation of biosynthesis of vermiculin and vermistatin in Penicillium vermiculatum. AB - Biosynthesis of vermiculin (1) and vermistatin (2) in Penicillium vermiculatum can be controlled by the carbon and nitrogen sources. Glucose and sucrose affect the levels of the two metabolites; cornsteep liquor influences the quality the biosynthesis. The concentrations of Fe3+ and Cu2+ ions also affect the biosynthesis, the effect being dependent on the type of carbon source utilized. The compounds capable of electron transport generally stimulate the production of 1 and 2 but do not influence the biosynthesis qualitatively. PMID- 1505864 TI - Effect of protein phosphorylation on the activity of RNA polymerase in streptomycetes. AB - RNA polymerase was isolated from Streptomyces granaticolor and protein kinase was partially purified from Streptomyces albus. When RNA polymerase was treated with protein kinase in vitro the activity of RNA polymerase was markedly enhanced. Furthermore, a protein of M = 65 kDa was isolated which, after being phosphorylated, stimulated RNA polymerase activity in vitro. Because neither the beta-subunits nor the alpha-subunits of RNA polymerase were phosphorylated it is assumed that phosphorylation of the 65 kDa protein may regulate the activity of RNA polymerase in streptomycetes. PMID- 1505865 TI - Use of whey for production of exocellular polysaccharide by a mutant strain of Xanthomonas campestris. AB - Growth and kinetics of the production of exocellular polysaccharide was studied in a mutant strain of Xanthomonas campestris lac+ during cultivation in a submerged culture in a medium containing whey. The maximum production of the polymer was observed at the initial stage of the stationary growth phase of the culture. The mean production yield was about 1.4%. The results were comparable with those obtained during cultivation on a lactose medium. PMID- 1505866 TI - Taxonomic studies of Streptomyces virginiae mutants overproducing virginiamycin M1. AB - By using both the traditional International Streptomycetes Project methods and chemical approaches followed by a hierarchical cluster analysis, Streptomyces virginiae mutants A-1 and B-43 (yielding higher amounts of the M1 component of virginiamycin complex), their wild ancestor ATCC 13161, and another virginiamycin producer, S. pristinaespiralis NRRL 2958, were subjected to taxonomic studies to find kinship or differences among the strains. Of the methods used, only the test of carbon utilization, investigation of spore surface and analysis of sugar constituents of cell walls proved to be reliable enough to demonstrate the species identity of S. virginiae strains and to distinguish them from S. pristinaespiralis. L,L-2,6-Diaminopimelic acid was present in all strains. Analysis of fatty acids and total proteins as well as investigations of morphology and pigmentation of agar cultures led to confusing results. PMID- 1505867 TI - Characteristics of Streptomyces globisporus strain 0234A forming endospores in submerged cultures. AB - Thermosensitive submerged endospores formed by Streptomyces globisporus 0234 and its natural variant A resembled those of thermoresistant actinomycetes not only in their morphology ultrastructure, but also in the content of dipicolinic acid. The production of endospores containing this substance is unusual in Streptomyces while other features of the strain indicate relatedness to other streptomycetes. Chemotaxonomic analysis of variant A revealed the cell wall to be of chemotype I and fatty acid content typical of Streptomyces. Most characteristics of surface cultures of variant A coincided with those of the original strain 0234 and its endosporeless variant B. Both the strain 0234 and its variants A and B produced identical antibiotics and pesticidal compounds. PMID- 1505868 TI - Degradation of the herbicide bromoxynil in Pseudomonas putida. AB - Biological conversion of the herbicide bromoxynil (3,5-dibromo-4 hydroxybenzonitrile) was studied in a batch culture of Pseudomonas putida by using HPLC. The process had a cometabolic character and proceeded only in the presence of another, simultaneously metabolizable, carbon and energy source. The intensity of degradation correlated with the growth rate, the degradation stopping when the cosubstrate becomes exhausted or the pH value of the medium falls below 6.5. In a medium with glucose, no lag phase longer than one day was observed concerning growth, sugar and herbicide consumption and formation of metabolic herbicide derivatives (3,5-dibromo-4-hydroxybenzamide and 3,5-dibromo-4 hydroxybenzoic acid). In a medium with ribose, the initial lag of the above processes took 2 d. No formation of other degradation products was detected. Growth inhibition was proportional to the concentration of bromoxynil. PMID- 1505869 TI - Effect of glucose and ribose on microbial degradation of the herbicide bromoxynil continuously added to soil. AB - Bromoxynil (3,5-dibromo-4-hydroxybenzonitrile) was continuously added to chernozem (Haplic typic) soil inoculated with a suspension of Pseudomonas putida capable of cometabolic decomposition of the compound in a hetero-continuous-flow cultivation setup. In the steady state, when glucose or ribose were simultaneously added, 90 and 47% of the added herbicide was degraded per day, respectively. If the saccharides were absent, only 10-27% of the herbicide was decomposed. Addition and removal of glucose feeding resulted in an increase and decrease, respectively, of the degradation intensity, irrespective of the amount of the bacterial decomposers present. Two degradation products, 3,5-dibromo-4 hydroxy-benzamide and 3,5-dibromo-4-hydroxybenzoic acid, were formed during cultivation. The total amount of bromine-containing compounds was reduced only in the presence of glucose. PMID- 1505870 TI - Phenomenological theory of substrate-induced acidification with application to Candida utilis dissimilating ethanol. AB - The mathematical theory of substrate-induced acidification by microorganisms was based on special formulation of mass and charge conservation laws for distinct species. The strength of the theory was tested on the ethanol-induced acidification by Candida utilis in pure water and in phthalate buffer. We showed that the theory may be used to approximate, extrapolate and predict the course of apparent acidification including the effects of buffering capacity of the broth. It makes it possible to formulate mathematical models that are suitable for process simulation and computer control of bioreactors when pH is used as a state variable. PMID- 1505871 TI - Adherence of intestinal and extraintestinal Pseudomonas aeruginosa to tissue culture cells. AB - The adherence pattern of Pseudomonas aeruginosa strains to HeLa, Vero and CHO cells was studied. The diffuse type of adherence was found to prevail on HeLa cells. It was characteristic for intestinal and environmental strains. Urinary strains revealed more often a localized adherence. A similar pattern was obtained with CHO cells. Experiments with Vero cells showed an equal distribution of intestinal strains regarding the diffuse, localized and mixed adherence. Urinary strains revealed mostly a localized adherence of a similar pattern as was observed on HeLa and CHO cells. PMID- 1505872 TI - Bacterial infection modulated by glucan: a search for the host defense potentiation mechanisms. AB - Interactions between bacteria and the host were studied from day 0 up to day 10 post-challenge in mice pretreated with soluble glucan (20 mg/kg i.p.) and challenged supralaryngeally with a virulent strain of Klebsiella pneumoniae. In the initial phase of infection, clearance of bacteria in the airways of glucan treated mice was improved to an extent comparable with the vaccinated group but, in contrast to the immunized animals, subsequent regrowth of the bacterial inoculum was not prevented. The efficacy of defense, based during the entire course of infection mainly upon phagocytosis by neutrophils, markedly increased at intervals corresponding to the onset of humoral immune response. No evidence was obtained to indicate an enhanced involvement of alveolar macrophages in the phagocytosis of bacteria in glucan-stimulated mice. The results further support the notion that improvement of specific immune responsiveness rather than activation of nonspecific effector functions might be the most important expression of the host-defense-potentiating capacity of glucan and related stimulants of microbial origin. PMID- 1505873 TI - Functional and metabolic changes of guinea pig peritoneal macrophages induced by bacterial vaccines. AB - Phagocytic activity of peritoneal macrophages of guinea pigs injected subcutaneously with bacterial vaccines was found to be increased. The phagocytic index remained unchanged or was decreased. In addition, a decreased candidacidal activity was observed. Metabolic activation of macrophages, measured by the INT test, was inhibited in unstimulated cells while cells stimulated with zymosan or opsonized zymosan exhibited higher values of the INT test as compared with control animals. After injection of vaccines the number of peritoneal macrophages was increased, but the spleen mass decreased. PMID- 1505874 TI - Effect of pH on the stability of type-C toxin of Clostridium botulinum. AB - Stability of type-C botulinum toxin at pH 1.8-12.0 and during exposure to 5 and 28 degrees C for 20 and 16 h, respectively, was tested by titration on adult mice. The toxin was found in the samples kept at pH of 2.7-10.2, whereas, at the pH extremes of 1.8 and 12.0, it was inactivated. PMID- 1505875 TI - Large-scale isolation and partial characterization of plasmid DNA from B. larvae. AB - Large-scale preparation of plasmid DNA from two Bacillus larvae strains 423 and 728, honey-bee pathogens, is described. The isolated plasmid DNAs were analyzed by restriction enzyme mapping. No difference in the resulting maps was found for six restriction enzymes. The plasmid DNAs were also compared by Southern blot hybridization and by electron microscopy. The results confirmed the identity of these plasmid DNAs. All these data suggest that B. larvae strains harbor the same plasmid. PMID- 1505876 TI - Electron-microscopic study of the effect of various extractants on the morphology of Coxiella burnetii. AB - This paper presents the results of the effect of trichloroacetic acid (TCA) at two different temperatures and the effect of a mixture of detergents (D) on Coxiella burnetii. Both TCA and D caused a large destruction of C. burnetii cells. In both cases complexes of high-molar-mass components from the outer membrane were extracted. In the D case not only proteins but a mixture with other high-molar-mass structures were released from the destroyed cells. By extraction of TCA, the antigenic complex composed of lipopolysaccharides (LPS), proteins and phospholipids was released. The effect of the D mixture on C. burnetii causes their complete destruction. The TCA causes a surface destruction of cells but it does not cause complete disintegration. The small-cell variants (SCV) in both cases were shown to be more stable compared to the large-cell variants (LCV). PMID- 1505877 TI - Growth and enzymological characteristics of a pink-pigmented facultative methylotroph Methylobacterium sp. MB1. AB - Growth characteristics of batch and continuous cultures of the pink facultative methylotroph Methylobacterium sp. MB1 were determined. The response of a chemostat culture to a pulse increase of methanol concentration was studied. Malate, succinate and oxaloacetate additions to the methanol-supplemented medium decreased batch culture growth inhibition by methanol. The carotenoid content in cells grown in a chemostat decreased with increasing growth rate. The key enzyme activities of C1-metabolism were measured in a chemostat culture at different dilution rates. PMID- 1505878 TI - Cloning of Candida boidinii DNA fragments promoting autonomous replication of plasmids in Saccharomyces cerevisiae. AB - Fragments of Candida boidinii chromosomal DNA were inserted into the integrative vector YIp-kanr and examined for the presence of sequences promoting autonomous replication of plasmids in Saccharomyces cerevisiae. Restriction maps of two plasmids, designated S6/4 and S6/5, originating from the same S. cerevisiae transformant, were constructed. Southern hybridization data confirmed that the plasmids carry sequences from the C. boidinii chromosome. Both plasmids transform S. cerevisiae strains at 4-5-fold higher frequency than cloning vectors based on the replication origin of the 2 microns plasmid. Mitotic stability of the constructed plasmids is similar to that of the 2 mu-based vector pNF2 in S. cerevisiae. PMID- 1505879 TI - Transformation of Streptomyces lincolnensis protoplasts with plasmid vectors. AB - A method for the preparation and regeneration of protoplasts of Streptomyces lincolnensis is described. Mycelium in the early exponential phase appeared to be most suitable for this purpose and yielded up to 25% regenerated intact cells. Transformation of S. lincolnensis protoplasts was achieved using broad-host-range streptomycete plasmid vectors pIJ622, pMP66, pRS410 and pIJ943 constructed from replicons pIJ101, pSLG33 and SCP2. The efficiency of transformation was 3.10(3) transformants per micrograms plasmid DNA when (2-5).10(7) recipient protoplasts were used. Interspecific transformations showed that there is no efficient restriction system in S. lincolnensis that would limit the transfer of genetic information from S. lividans or E. coli. PMID- 1505880 TI - Comparison of permuted region lengths in the genomes of related Salmonella typhimurium phages P22 and L. AB - Lengths of permuted regions in the P22 and L phage genomes were estimated from the relative yields of DNA in many electrophoretic bands obtained using several restriction endonucleases. It was found that 3.6 kb (8.7%) of P22-DNA and 7.2 kb (17.8%) of L-DNA were circularly permuted. In both phages the sequential packaging process proceeded in the same direction and four headful-size DNA molecules were, on the average, cleaved in one packaging series. The differences in circular permutation may originate from different genome lengths because their average headful portions are very similar (42.5 kb in P22 and 42.3 kb in L). PMID- 1505881 TI - Construction of a new Escherichia coli-Saccharomyces cerevisiae shuttle plasmid cloning vector allowing positive selection for cloned fragments. AB - A new E. coli-S. cerevisiae shuttle plasmid cloning vector (pPW263) with a positive type of selection, was constructed. The selection system, based on the regulatory region of lambda phage controlling the expression of tetracycline resistance, was derived from the cloning vector pUN121 (Nilsson et al. 1983). There are three cloning sites in the cI gene, EcoRI, HindIII and BglII, and, in addition, two unique sites in the neighborhood, BamHI and SalI. The size of the vector is 7.8 kb. The maintenance of the vector and the selection in yeast was ensured by the replication region of the 2 mu plasmid and by the URA3 marker gene, respectively. PMID- 1505882 TI - Purification of the cellulase complex produced by Penicillium camemberti and its partial characterization. AB - Three cellulase components (FP-ase, CMC-ase and cellobiase) were purified by affinity binding on Avicel followed by Sephadex G-25, DEAE-Sepharose, DEAE cellulose and Sephadex G-100 chromatography from the culture filtrate of the newly isolated strain Penicillium camemberti. The isolated enzymes had the properties of cellobiohydrolase, endo-1,4-beta-D-glucanase and cellobiase and their respective molar masses were 99, 87 and 61 kDa as determined by molecular sieve chromatography on Sephadex G-100. The amino acid composition of each fraction was also determined. PMID- 1505883 TI - Purification and kinetics of extracellular phospholipase A of Salmonella newport. AB - Attempts were made to purify and study the kinetics of extracellular phospholipase A of Salmonella newport (6,8, eb; 1,2). The enzyme was purified by salt precipitation followed by gel filtration, using different grades of Sephadex. The enzymically active purified preparation was found to be a protein, having molar mass ranging between 43 and 67 kDa. The enzyme had a pH optimum at 7.5, giving 18.2 micrograms of lysophosphatidylcholine per mg protein. Its activity was enhanced by all metal ions except potassium, by solvents and surfactants except sodium dodecyl sulfate. It hydrolyzed the membrane phospholipids of red blood cells and was inhibitory to the growth of other microorganisms. PMID- 1505884 TI - Construction and use of Agrobacterium tumefaciens binary vectors with A. tumefaciens C58 T-DNA genes. AB - Five plant morphoregulatory genes were isolated from the Agrobacterium tumefaciens Ti plasmid and binary plasmid vectors for plant transformation with these genes were constructed. All vectors have a similar structure with T-DNA borders, RK2 origin of replication and chimeric kanamycin resistance gene for the selection of transformed plant tissues. Over twenty vectors with single and combined morphoregulatory genes were constructed and their effects after tobacco tissue transformation studied. PMID- 1505885 TI - Viability of basidiospores of Agrocybe cylindracea and Oudemansiella mucida and antibiotic activity of monosporic isolates in the course of 15 years of storage. AB - Basidiospores of Agrocybe cylindracea were found to be viable for 12 years, those of Oudemansiella mucida for 6 years. The ability of monosporic isolates from these spores to produce antibiotics has been partly preserved. PMID- 1505886 TI - Screening for a new generation of anthelminthic compounds. In vitro selection of the nematode Caenorhabditis elegans for ivermectin resistance. AB - Development of resistance to ivermectin in vitro is reported for the first time. Two strains of Caenorhabditis elegans D5 and D6 able to grow on agar plates after treating with up to 3 mg ivermectin per L were selected. The parent strain N2 was extremely sensitive to ivermectin, its growth being inhibited by treatment with 0.1-0.2 mg IVM per L. PMID- 1505887 TI - Imidazoline receptors: historical perspective. PMID- 1505888 TI - Restorative resection for cancer of the rectum. AB - The importance of sphincter preservation in the surgical treatment of rectal cancer was emphasized more than a century ago. Combining these techniques with adequate anterior resection has permitted restorative resection in the treatment of most rectal cancers. Miles' abdominoperineal resection is now being used much less frequently. In this review, the pertinent technical factors, patient selection and current issues relevant to restorative resection of the rectum are presented. PMID- 1505889 TI - Coloanal anastomosis following low anterior resection. AB - Low anterior resection with coloanal reconstruction is indicated for rectal cancer when APR is not necessary and conventional LAR is not possible. LAR/CAA, in properly selected patients, yields results equivalent to those achieved with APR, since it encompasses equally the primary routes for regional spread. Most patients with midrectal tumors are candidates for LAR/CAA if an intrapelvic anastomosis is technically impossible. Complete dissection of the rectum and its mesentery to the anal hiatus of the pelvic diaphragm is essential for optimal cancer treatment and appropriate selection of cases for sphincter preservation. Careful attention to five technical points are essential for a successful outcome with respect to survival and function: (1) complete mobilization of the left colon; (2) sharp dissection; (3) restoration of the anorectal right angle and complete sacralization of the transposed colonic segment; (4) meticulous pelvic hemostasis and drainage to avoid septic complications; (5) routine use of diverting colostomy until completion of healing. In the long run, the LAR/CAA offers patients good function with few side effects and is universally preferable to a permanent colostomy. By avoiding permanent colostomy, cancer treatment is improved without compromising survival. PMID- 1505890 TI - Abdominosacral resection for midrectal cancer. AB - Abdominosacral resection is the most reliable radical sphincter-saving operation for midrectal cancers which are too low for anterior resection. The posterior incision provides maximum exposure for wide resection of the tumor, a measured distal margin, and an accurate anastomosis. The procedure can be carried out consistently to the pelvic floor without disrupting the anal sphincters and their innervation. Sphincter function is consistently preserved. Mortality rate is no higher than for other radical rectal resections. Morbidity can be limited by the selective use of protective colostomy. The use of mechanical retractors and the end-to-end stapler facilitates the operation and should encourage its wider application. The transsacral approach allows mobilization of the rectum to the levators in every case, and resection is limited only by the distance of the tumor from the sphincter, and not by poor exposure due to obesity or a narrow pelvis. In the treatment of 926 consecutive patients with rectal cancer, sphincter-saving resection was possible in 79%. In our experience, abdominosacral resection extends the range of sphincter-saving resection beyond that which is possible by the abdominal approach alone, with no compromise in safety and no increased risk of local recurrence or death from cancer. PMID- 1505891 TI - Local excision of early rectal cancer. AB - During the past 15 years, data from numerous multimodality trials have shown significant improvement in outlook for patients with "high risk" colon and rectum cancers. In this paper, a suggested next step is to use the advance in multiple treatment approach to challenge the major toxicity of treatment in patients with rectum cancer--the permanent colostomy. PMID- 1505892 TI - Adjuvant therapy in rectal cancer. AB - Local failure in the pelvis following radical surgery for rectal cancer produces severe morbidity and responds poorly to subsequent therapy. Overall, 25% of rectal cancer patients will recur in the pelvis. The use of adjuvant pelvic radiation therapy combined with systemic chemotherapy is effective in reducing the incidence of local recurrence as well as subsequent distant metastases. Current clinical trials are evaluating various radiation-chemotherapy-surgical interactions as well as the most efficacious chemotherapy program. PMID- 1505893 TI - Prognostic significance of ploidy determination in rectal cancer. AB - Between 1965 and 1981, 154 patients with potentially curable rectal adenocarcinoma underwent surgical treatment at the University of Chicago Medical Center. In 134 cases, enough histological material was available to perform determinations of DNA content by the cytophotometric method (n = 108), or by the flow cytometric technique (n = 109). In 83 cases, DNA content was analyzed in the same specimen with both techniques, and in 77 of these cases the sections obtained from the paraffin blocks were contiguous. When using flow cytometry, 62% of stage B and 74% of stage C lesions were classified as aneuploid on the basis of a DNA index greater than 1. This correlation was statistically significant (p = 0.002). Patients with diploid tumors had an actuarial five-year survival equal to 62% in comparison with a 46-51% five-year survival for patients with aneuploid tumors. This difference was not statistically significant and it was explained by the tendency for aneuploid tumors to be in an advanced histopathological stage. PMID- 1505894 TI - Genetic abnormalities of colorectal carcinoma. PMID- 1505895 TI - Morbidity and mortality after surgical resection of liver tumors. Analysis of 229 cases. AB - Two hundred and twenty-nine resections of hepatic tumors were performed over the past 10 years. The intraoperative death rate, 30-day operative mortality and major complication rate were 1.3%, 8.3% and 20%, respectively. Both morbidity and mortality were significantly related to the type of surgery and to the extent of the resection to contiguous organs and/or structures. Cirrhotic patients (40% in hepatocellular carcinoma) had a higher mortality rate (19%). Intraoperative blood loss was related to the extent of the resection and was significantly higher in patients with major complications and/or death. The main problem was postoperative liver failure in cirrhotic patients, which is difficult to predict and to treat. PMID- 1505896 TI - Gastric microcirculation and acute gastric mucosal lesions in patients with hepatic cirrhosis. AB - We endoscopically investigated gastric microcirculation using a laser-Doppler flowmeter and acute gastric mucosal lesions (AGML) during a 3-year follow-up period in patients with hepatic cirrhosis. Gastric microcirculation tends to decrease in patients with hepatic cirrhosis, especially when gastric mucosal hemorrhage or mucosal petechiae are observed endoscopically. Total gastric resection was performed for gastric hemorrhage due to AGML in three patients, two of whom had good liver function--Child's grade A--and survived more than 5 years with a good quality of life, but one patient with Child's grade C experienced poor quality of life and died within 2 years after surgery. We conclude that decreased gastric microcirculation plays a role in the occurrence of AGML in patients with hepatic cirrhosis. Total gastric resection should be carefully considered for hemorrhagic gastritis in patients with Child's grade C hepatic cirrhosis. PMID- 1505897 TI - Synthesis of eicosanoids by circulating mononuclears in healthy people and in patients with liver cirrhosis. AB - The synthesis of some of the products of cycloxygenase and lipoxygenase metabolism of arachidonic acid (AA) in mononuclear cells (MNCs) in vitro was studied with [3H]AA in five healthy subjects and five patients with liver cirrhosis (LC). FGA, ionophor Ca A23187 and levamisole were investigated. The eicosanoid synthesis by non-stimulated MNCs of the patients was normal. Mitogens augmented the outcome of PGs, TXB2 and HETE and increased the outcome of LTB4 in comparison with the control group. In liver pathology prostanoid and LT synthesis differed. In patients, but not in healthy subjects, prednisone suppressed eicosanoid production stimulated by FGA and reduced LTB4 and HETE outcome in MNCs treated by ionophor. The role of LTB4 hyperproduction in the pathogenesis of LC and the possibility of prednisone-induced suppression of synthesis of lipoxygenase metabolites in MNCs are discussed. PMID- 1505898 TI - Damage and repair of hepatocyte nuclear DNA after hepatic inflow occlusion. AB - Recent reports emphasize that ischemic tissue damage is caused mainly by superoxide produced at the reperfusion rather than by ischemia itself. In this paper, the damage and repair of hepatocyte nuclear DNA of is investigated using rats with portasystemic shunt. Hepatic inflow was occluded for 30, 60 and two times 30 (with a 10-minute interval) minutes. Extent of DNA damage and repair were measured by nick-translation and 3H-thymidine incorporation, respectively. Superoxide, GOT and endotoxin were also measured. The results are as follows. 1. Sixty minutes of ischemia produced more serious DNA damage of the hepatocyte nucleus and a significant delay in repair as compared with 30 minutes of ischemia. 2. Intermittent ischemia for two times 30 minutes produced milder damage to DNA, and earlier recovery than a single ischemia of 60 minutes. 3. Serum and tissue peroxide increased after reperfusion in 60 minutes and intermittent ischemia, but not after 30 minutes of ischemia. Endotoxin level increased only in 60-minute ischemia. Histological change, neutrophilic cell infiltration, was most prominent in 60-minute ischemia. On the basis of these data, insofar as the duration of ischemia is not so long that cell damage becomes irreversible, damage by superoxide after reperfusion will be negligible. Therefore, intermittent short-term inflow occlusion is preferable in hepatic surgery. PMID- 1505899 TI - Stones in a long pancreaticobiliary common channel: a rare cause of obstructive jaundice and pancreatitis. AB - A case of obstructive jaundice associated with acute pancreatitis is reported. The underlying cause was a dilated long pancreaticobiliary common channel impacted with stones and bile debris. There was no stone in the rest of the biliary system except for one in the lowest part of the common bile duct and the overall appearance of the stones suggested that they originated within the common channel itself. A long common channel may be an underlying cause of various pathological conditions in the pancreaticobiliary system. Early operative intervention is recommended when such a diagnosis is made. PMID- 1505900 TI - Postoperative chemotherapy and follow-up program in colon cancer with high serum CEA level. AB - We present a patient with colon cancer who had a high serum CEA level without detectable liver metastases at surgery. He underwent hepatic arterial infusional chemotherapy for suspicious liver metastasis concomitant with colon resection at the initial operation. He was followed closely by monitoring the serum CEA levels as well as abdominal US and CT. Five months after the first operation, a small but apparent metastatic lesion was detected in the liver, for which curative resection was performed. The importance of postoperative management with chemotherapy for occult metastases in the liver and close follow-up by CEA monitoring is discussed for such a patient. PMID- 1505901 TI - Neoplastic Paneth cells in adenocarcinoma of the stomach: a case report. AB - A case of well-differentiated (intestinal type) adenocarcinoma of the stomach in a 73-year-old man is reported. The tumor contained Paneth-like cells as an integrated part, and their identity at the light microscopic level was confirmed by histochemical stains including an immunohistochemical stain for lysozyme. This case is unusual, since neoplastic Paneth cells occur only rarely in adenocarcinomas of the stomach. PMID- 1505902 TI - Al-type generalized amyloidosis showing a solitary duodenal tumor. AB - An amyloid tumor of the duodenum is a rare occurrence. A patient who presented with epigastric discomfort, in whom a barium meal study revealed a tumor of the duodenum is described. Upper gastrointestinal endoscopy showed a submucosal location of the tumor, and examination of a biopsy revealed amyloid deposition of the AL type. Diffuse tumor involvement of adjacent tissues of the duodenum and also deposits of amyloid fibrils in the liver and skin with no evidence of a chronic pre- existing disease in the patient led to the diagnosis of primary systemic amyloidosis. The distinguishing feature of this case was the formation of a solitary and relatively large tumor in the duodenum mimicking a submucosal tumor, which is in contrast to most reported cases of multiple and smaller amyloid tumors in other parts of the gastrointestinal tract. PMID- 1505903 TI - Effects of growth hormone in patients receiving total parenteral nutrition following major gastrointestinal surgery. AB - The purpose of the present study was to determine whether the administration of a biosynthetic human growth hormone was capable of enhancing the efficacy of total parenteral nutrition. Patients (n = 38) who had undergone major gastrointestinal surgery were randomly divided into two groups. Group I (n = 20) treated only with PN, and Group II (n = 18) treated as in Group I plus human growth hormone (4 IU daily). Our study shows that the administration of human growth hormone produces a statistically significant increase in serum levels of growth hormone, somatomedin-C, transferrin, albumin and total proteins. It also causes a positive nitrogen balance from the first 24 hours onward. These findings suggest that the administration of human growth hormone produces an increase in protein synthesis, perhaps through somatomedin-C as mediator. PMID- 1505904 TI - Ranitidine and antacids in the prevention of duodenal ulcer relapse in Greece. AB - The present study was undertaken to compare the efficacy of ranitidine 150 mg/nocte with that of antacids taken "on demand" in the prevention of recurrence of duodenal ulcer (DU). Two groups (A, B) of patients with DU recently healed by ranitidine or antacids were studied. Patients of Group A (110) healed by ranitidine were put on maintenance treatment with ranitide, and patients of Group B (32) healed by antacids were given antacids "on demand" for a period of one year. Endoscopy was performed at the end of the 6th and 12th months, as well as whenever symptoms appeared. Patients were followed up clinically at 2-month intervals. Relapse rates of 11% (group A) and 34% (group B) were found at the end of the 6th month, (p less than 0.005), while the total relapse rates at the end of the 12th month were 19% and 47%, respectively (p less than 0.005). Recurrences were asymptomatic in 62% (Group A) and 27% (Group B) of patients. No significant side effects were observed. It is concluded that ranitidine 150 mg nocte is significantly superior to antacids "on demand" as far as the recurrence of DU is concerned. PMID- 1505905 TI - A case of liver cirrhosis with an unusual portosystemic shunt via the right testicular vein. AB - We report a case of liver cirrhosis with a rare portosystemic shunt via the right testicular vein. Angiographic examination demonstrated two major hepatofugal collateral pathways. First, the enlarged and tortous left gastric and short gastric veins which drain into the left renal vein after forming varices in the stomach. Second, the superior mesenteric vein forms the large mesenteric varices which drain into the inferior vena cava via the enlarged right testicular vein, which is a very rare shunt. PMID- 1505906 TI - 31st annual meeting of the European Society for Paediatric Endocrinology (ESPE). Zaragoza, September 6-9, 1992. Abstracts. PMID- 1505907 TI - A pilot study of ribavirin therapy for chronic hepatitis C. AB - Interferon-alpha therapy is of proven efficacy in chronic hepatitis C, but it is not universally effective and may be associated with intolerable side effects. Ribavirin is a nucleoside analog with a broad spectrum of antiviral action. We conducted an uncontrolled pilot study of ribavirin therapy in 13 patients with chronic hepatitis C. Ribavirin was given for 6 mo, in a dose that was increased, at 2-mo intervals, from 600 mg to 1,000 mg to 1,200 mg/day. Serum ALT levels gradually decreased in all 13 treated patients; the mean percentage of decrease was 67% (from 210 U/L [range = 109 to 593] to 63 U/L [range = 22 to 108 U/L]; p = 0.0006) after 6 mo of treatment. Serum aminotransferase levels fell to the normal range in four patients (31%). In the 3 to 6 mo after cessation of ribavirin therapy, serum aminotransferase activities gradually rose to near pretreatment levels in all but one patient. Therapy was associated with a significant decrease in the geometric mean titer of hepatitis C virus RNA in serum (1:1,981 vs. 1:199; p less than 0.02) although no patients lost hepatitis C virus RNA from serum during therapy. No significant improvement was seen in liver histological appearance. Ribavirin therapy resulted in mild, reversible hemolysis; no patient exhibited symptomatic anemia. These findings suggest that ribavirin has a beneficial effect in patients with chronic hepatitis C, although further studies are needed to determine how ribavirin is best used. PMID- 1505908 TI - HBsAg retention sensitizes the hepatocyte to injury by physiological concentrations of interferon-gamma. AB - The role that inflammatory cytokines may play in the life cycle of the hepatitis B virus and in the pathogenesis of its associated liver disease has not been carefully delineated. In this report, we demonstrate that bacterial lipopolysaccharide, a potent inducer of inflammatory cytokines in vivo, causes a severe acute liver disease in transgenic mice whose hepatocytes produce the hepatitis B virus large envelope polypeptide and retain HBsAg within the endoplasmic reticulum. In contrast, 100-fold higher doses of bacterial lipopolysaccharide do not induce liver cell injury in nontransgenic littermate controls or in transgenic mice whose hepatocytes secrete HBsAg rather than retain it. Coincident with the hepatocellular injury and the influx of inflammatory cells into the liver, a marked reduction occurs in the intrahepatic content of hepatitis B virus steady-state messenger RNA, thereby confirming the selectivity of this process for the HBsAg-positive hepatocyte. Bacterial lipopolysaccharide induced hepatocellular injury appears to be principally mediated by interferon gamma because it can be markedly reduced by the prior administration of neutralizing interferon-gamma-specific monoclonal antibodies and because recombinant interferon-gamma is also selectively cytotoxic for the HBsAg-positive transgenic hepatocyte in vivo. Tumor necrosis factor-alpha is also involved in this process because bacterial lipopolysaccharide-induced liver cell injury is significantly reduced by tumor necrosis factor-alpha specific monoclonal antibodies. The role of tumor necrosis factor-alpha in bacterial lipopolysaccharide-induced liver cell injury is less clear than interferon-gamma, however, because unlike interferon-gamma it is also toxic for nontransgenic hepatocytes.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1505909 TI - Increased spontaneous and lymphokine-conditioned IgA and IgG synthesis by B cells from alcoholic cirrhotic patients. AB - Immunoglobulin secretion by B lymphocytes is a complex process in which lymphokines secreted by T lymphocytes play an important regulatory role. Increased serum levels of IgA and IgG have been characteristically detected in patients with alcoholic cirrhosis. We have studied the functional alterations of T and B lymphocytes implicated in the physiopathology of this common immunoglobulin abnormality. After activation with phytohemagglutinin, purified T cells from alcoholic cirrhotic patients showed significantly enhanced secretion of B-cell differentiation factors for IgG and IgA with respect to those secreted by T cells from healthy controls (p less than 0.05). Simultaneously, normal secretion of B-cell differentiation factor for IgM was demonstrated in T lymphocytes from these patients. The pattern of secretion of the lymphokines involved in the regulation of the B-cell differentiation pathway found in alcoholic cirrhotic patients was different from that of the primary biliary cirrhotic patients studied. Purified B cells from patients with alcoholic cirrhosis secreted significantly higher amounts of IgA and IgG than did those found in healthy controls, both spontaneously (p less than 0.05) and after sequential activation with immunoglobulin ligands (Staphylococcus aureus Cowan I) and a standard B-cell differentiation factor preparation (p less than 0.05). By contrast, the IgM secretion and regulatory pathway were normal in alcoholic cirrhotic patients. These results support a physiopathological explanation for the characteristic hyperimmunoglobulinemia found in patients with alcoholic cirrhosis. PMID- 1505910 TI - A clinicopathological study of human liver allograft recipients harboring preformed IgG lymphocytotoxic antibodies. AB - Twenty-six adult patients with preformed IgG donor lymphocytotoxic antibodies received primary liver allografts under FK 506 immunosuppression. The effect of the crossmatch-positive state on early graft function and on the immunopathological and histopathological findings was compared with that of 52 crossmatch-negative control recipients. The presensitized (crossmatch-positive) patients had prolongation of early graft dysfunction, underwent more clinically indicated biopsies and had a higher incidence of cellular rejection, both overall (p less than 0.05) and within 10 days of transplantation (p less than 0.01). They also had a higher incidence of graft failure in the first 180 days (p less than 0.01). Hyperacute rejection with necrotizing or neutrophilic arteritis was not seen in the crossmatch-positive grafts. However, histological findings associated with presensitization included platelet margination in central veins and sinusoids in biopsy specimens 60 to 90 min after graft revascularization. Later biopsy specimens had neutrophilic portal venulitis followed by cholangiolar proliferation, acute cholangiolitis and centrilobular hepatocyte swelling that mimicked preservation injury, endothelial activation of arteries with medial changes and relapsing episodes of acute cellular rejection. These clinicopathological observations suggest that lymphocytotoxic antibodies can have a deleterious effect on liver allograft function and survival, even if they do not precipitate immediate or hyperacute rejection. PMID- 1505911 TI - Localization of cytochrome P-450 gene expression in normal and diseased human liver by in situ hybridization of wax-embedded archival material. AB - The localization of the expression of several cytochrome P-450 genes in normal and diseased human liver was investigated by in situ hybridization of formalin fixed, paraffin wax-embedded archival tissue samples with 35S-labeled antisense RNA probes. The results demonstrated that genes coding for members of the cytochrome P-450 3A subfamily (CYP3A) were preferentially expressed in hepatocytes in acinar zone 3 (the centrilobular region), whereas genes coding for CYP1A2, CYP2A, 2B and 2C were expressed uniformly throughout the liver acinus. In cirrhotic livers, CYP2A and 2B genes (and to a lesser extent, CYP3A genes) were highly expressed in isolated hepatocytes located at the junction of parenchyma with fibrous septa. The cause and significance of the position-dependent expression of specific cytochrome P-450 genes in normal and diseased human liver are discussed. PMID- 1505912 TI - Biochemical and histopathological correlation in liver transplant: the first 180 days. AB - It is not known whether the histopathology of the liver allograft can be predicted from biochemical measurements in serum with the same confidence as in the native liver. To answer this question we compared the histopathological diagnoses in 170 biopsy specimens from 70 adult transplant recipients obtained during the first 180 days, with the concentrations of the serum bilirubin and the activities of AST, ALT and alkaline phosphatase measured at the same time. The most frequent diagnosis was cholestasis (n = 45), which was mild, moderate or severe and which may have been complicated by rejection (n = 28) or ischemia (n = 14). Hepatitis (n = 14), ischemia with rejection (n = 6) and spotty focal necrosis (n = 6) were diagnosed less frequently. Fifteen biopsy specimens were reported as histopathologically normal. In general, biochemical measurements discriminated poorly between different histopathological diagnoses. The histopathologically normal liver often showed an abnormal pattern of enzymes and an increase in the serum bilirubin level. As a result histopathologically normal biopsy specimens were indistinguishable biochemically from those with hepatitis. When two pathological conditions were found to coexist (e.g., cholestasis with either rejection or ischemic necrosis, or ischemic necrosis with rejection), the effect on the serum biochemistry was usually not additive and in some instances returned the biochemical abnormalities toward normal. With the exception of the serum bilirubin level, which increased with the severity of uncomplicated cholestasis, we could not identify a specific pattern of biochemical changes corresponding to a given histopathological diagnosis.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1505913 TI - Ursodeoxycholic acid for treatment of primary sclerosing cholangitis: a placebo controlled trial. AB - The efficacy and safety of ursodeoxycholic acid for the treatment of primary sclerosing cholangitis were evaluated in a prospective, randomized, double-blind, placebo-controlled trial. Fourteen patients with primary sclerosing cholangitis documented by cholestatic serum enzyme pattern, liver histological appearance and endoscopic retrograde cholangiography were included in the trial. Six patients received ursodeoxycholic acid (13 to 15 mg/kg body wt/day), and eight patients received placebo. Two patients had to be withdrawn from the study, one because of UDCA-related diarrhea and the other because of worsening of the disease during placebo treatment. Patients in the ursodeoxycholic acid group improved significantly during 1 yr of treatment with respect to serum levels of bilirubin (median = -50%), alkaline phosphatase (median = -67%), gamma-glutamyltransferase (median = -53%), AST (median = -54%) and ALT (median = -36%) compared with the placebo group, but not with respect to serum levels of hydrophobic bile acids. During ursodeoxycholic acid treatment, histopathological features also improved significantly, as evaluated by multiparametric score. Expression of human leukocyte antigen class I molecules appeared to be markedly reduced on liver cells after ursodeoxycholic acid treatment. We conclude that ursodeoxycholic acid is beneficial in reducing disease activity in patients with primary sclerosing cholangitis. PMID- 1505914 TI - Hemodynamics during liver transplantation: the interactions between cardiac output and portal venous and hepatic arterial flows. AB - Liver blood flow and systemic hemodynamics were measured intraoperatively in 34 patients after liver transplantation. Ultrasound transit-time flow probes measured hepatic arterial and portal venous flow over 10 to 75 min 1 to 3 hr after reperfusion. Cardiac output was measured by thermodilution. Mean cardiac output was 9.5 +/- 2.8 L/min; the mean total liver blood flow of 2,091 +/- 932 ml/min was 23% +/- 11% of cardiac output. Mean portal flow of 1,808 +/- 929 ml/min was disproportionately high at 85% +/- 10% of total liver blood flow. Correlation analysis showed a significant (p less than 0.01; r = 0.42) correlation between cardiac output and portal venous flow and a trend toward negative correlation (p = 0.087) between cardiac output and hepatic arterial flow. These data show that increased flow in the newly transplanted liver is predominantly portal venous flow and is associated with high cardiac output and reduced hepatic arterial flow. In the last 13 patients studied, portal flow was reduced by 50% and the hepatic artery response was measured. We saw a significant (p less than 0.05) increase in hepatic artery flow from 322 +/- 228 to 419 +/- 271 ml/min, indicating an intact hepatic arterial buffer response. The hepatic artery response also showed that it is a reversible rather than a fixed resistance that contributes to the low hepatic artery flow in these patients. PMID- 1505915 TI - Differential effects of chenodeoxycholic and ursodeoxycholic acids on interleukin 1, interleukin 6 and tumor necrosis factor-alpha production by monocytes. AB - Cell-mediated immunity and macrophage activity, especially that of Kupffer cells, are impaired during cholestasis. Some evidence exists that bile acids play a role in these immune defects. The purpose of this study was to evaluate the effects of individual bile acids on immunity and to determine whether monocytes could be a target. We assessed the effects of chenodeoxycholic acid, an endogenous bile acid, ursodeoxycholic acid, which has been shown to partially correct the immunological abnormalities observed in primary biliary cirrhosis, and their tauroconjugates on the production of interleukin-1, interleukin-6 and tumor necrosis factor-alpha. Chenodeoxycholic acid had a dose-dependent inhibitory effect on interleukin-1 (inhibitory concentration 50% = 60 mumol/L), interleukin 6 (inhibitory concentration 50% = 80 mumol/L) and tumor necrosis factor-alpha (inhibitory concentration 50% = 80 mumol/L) production; inhibition was almost complete at 250 mumol/L. In contrast, ursodeoxycholic acid had lesser or minimal inhibitory effects (inhibitory concentration 50% = 100 mumol/L for interleukin-1 and above 200 mumol/L for interleukin-6 and tumor necrosis factor-alpha). The inhibitory effects of taurochenodeoxy-cholic acid and tauroursodeoxycholic acid were similar to those of chenodeoxycholic acid and ursodeoxycholic acid, respectively. Ursodeoxycholic acid did not reverse the chenodeoxycholic acid induced inhibition of interleukin-6 or tumor necrosis factor-alpha production. In conclusion, chenodeoxycholic acid exerts strong inhibitory effects on monocyte activity in vitro, whereas the effects of ursodeoxycholic acid are minor. PMID- 1505916 TI - Incidence and predictive factors of first episode of spontaneous bacterial peritonitis in cirrhosis with ascites: relevance of ascitic fluid protein concentration. AB - To investigate the long-term probability of the appearance of the first episode of spontaneous bacterial peritonitis in cirrhosis with ascites and to identify predictors of this complication, we closely followed throughout their illness 127 patients consecutively admitted to our unit for the treatment of an episode of ascites without prior spontaneous bacterial peritonitis (follow-up period: 21 +/- 22 mo). Thirteen patients (10%) had the first spontaneous bacterial peritonitis episode during follow-up. The appearance probability of this complication is 11% at 1 yr and 15% at 3 yr. Thirty-three variables obtained at admission (including clinical data, standard liver and kidney function test results, ascitic fluid protein concentrations and hemodynamic parameters) were analyzed in relation to their value in predicting spontaneous bacterial peritonitis development. In univariate analysis (Kaplan-Meier curves) five variables reached statistical significance (p less than 0.05) as predictive factors for the development of the first spontaneous bacterial peritonitis episode. These five variables were poor nutritional status, increased serum bilirubin levels, increased serum AST levels, decreased prothrombin activity and reduced total protein concentration in ascitic fluid. When these five variables were introduced in a multivariate analysis, only the ascitic fluid protein concentration was found to correlate independently with spontaneous bacterial peritonitis development (p = 0.002). The probability of first spontaneous bacterial peritonitis after 3 yr of follow-up was 24% and 4% in patients with ascitic fluid protein content lower than 1 gm/dl and greater than or equal to 1 gm/dl, respectively.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1505917 TI - Fraternal concordance of types of abnormal hepatocellular mitochondria in Wilson's disease. AB - Three distinct patterns of structural abnormalities of mitochondria, indicated as types I, II and III and associated with steatosis, were identified in the hepatocytes of 40 of 42 asymptomatic and 8 of 22 symptomatic patients with documented Wilson's disease before treatment. No correlation was seen between the type of mitochondrial abnormality and the patient's age, hepatic copper concentration, degree of hepatic steatosis or serum aminotransferase level. However, comparison of the types of abnormal hepatocellular mitochondria displayed by five pairs and one trio of asymptomatic siblings revealed remarkably similar types of abnormalities in each family. The variety of mitochondrial types encountered in different families and the high degree of type identity in sibling relationships indicate that the structural changes are genetically determined. PMID- 1505918 TI - Reversible inhibition of albumin production by rat hepatocytes maintained on a laminin-rich gel (Engelbreth-Holm-Swarm) in response to secretory products of Kupffer cells and cytokines. AB - Decreased albumin synthesis by hepatocytes in liver injury is thought to occur in response to Kupffer cell-derived acute-phase cytokines. In this study we used hepatocytes maintained in a differentiated phenotype, by culture on a laminin rich gel substratum (Engelbreth-Holm-Swarm matrix), to investigate the effects of Kupffer cell-conditioned medium and purified cytokines (interleukin-1, interleukin-6 and tumor necrosis factor-alpha) on albumin synthesis. Kupffer cell conditioned medium caused a reversible decrease in albumin synthesis to 64.7% of control (p less than 0.01, Wilcoxon's rank sum test, n = 11) on day 2. Repeated doses caused further dose-dependent reversible responses. The same result was obtained when protease inhibitors (alpha 1-antitrypsin and alpha 2-macroglobulin) were added to Kupffer cell-conditioned medium (n = 3), thus eliminating the potential effect of matrix degradation. Pure interleukin-1, interleukin-6 and tumor necrosis factor-alpha also inhibited albumin synthesis (p less than 0.05, Wilcoxon's rank sum test, n = 5), interleukin-6 having the greatest effect. After exposure to interleukin-1 (30 U.ml-1) and tumor necrosis factor-alpha (300 U.ml 1), decreased albumin synthesis was followed by a rebound increase (n = 3). Our results support the hypothesis that reduced albumin synthesis in the acute-phase response is modulated by cytokines released from Kupffer cells. Moreover, our results suggest that hepatocytes may exhibit a compensatory increase in albumin synthesis after cytokine withdrawal. These findings may be of physiological importance in the recovery from injury and the acute-phase response in vivo. PMID- 1505919 TI - Loss of mitochondrial respiratory function and its suppression during cold ischemic preservation of rat livers with University of Wisconsin solution. AB - Preservation of the liver involves a period of cold (0 degrees to 4 degrees C) ischemia; the longer the ischemic period, the greater the injury to the liver. The mechanisms for cold-induced ischemic injury are not known, but it is clear that after preservation the liver has a reduced capacity to regenerate high energy phosphate compounds (ATP). One cause for the delayed rate of ATP synthesis could be injury to the mitochondria. The effects of long-term (more than 24 hr) preservation on liver mitochondrial function have not been previously studied. In this study, rat livers were preserved in University of Wisconsin solution at 4 degrees C for up to 96 hr. After preservation, mitochondrial respiratory function was assayed in a homogenate and in isolated mitochondria. We saw a progressive increase in oligomycin-sensitive respiration with time of preservation (from 1.2 +/- 0.09 mumol.min-1.gm tissue-1 at 0 hr to 3.8 +/- 0.2 mumol.min-1.gm tissue-1 after 96 hr). The increase after 24-hr preservation (2.1 +/- 0.2 mumol.min-1.gm tissue-1) was also significantly greater than 0 time values (p less than 0.05). No decrease was found in uncoupler-stimulated respiration for up to 48 hr of preservation; only a small decrease was seen after 72 hr of preservation (about 30%). The cause of the increase in oligomycin-sensitive respiration appeared to be related to free fatty acids (or another uncoupling factor) generated during preservation. This was suggested from the fact that bovine serum albumin prevented the increase in oligomycin-sensitive respiration after all periods of preservation.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1505920 TI - Flow-limited tracer oxygen distribution in the isolated perfused rat liver: effects of temperature and hematocrit. AB - We used the multiple-indicator dilution technique to examine the kinetics of tracer oxygen distribution and uptake in the rat liver perfused in a nonrecirculating fashion with blood. 51Cr-labeled 18O2-saturated erythrocytes, labeled albumin, sucrose and water (the tracers for oxygen and vascular, interstitial and cellular references) were injected simultaneously into the portal vein. Timed anaerobic samples were collected from the hepatic vein and analyzed by mass spectrometry for relative 18O2 enrichment and radioactivity. In a set of experiments performed at 32 degrees C, oxygen uptake was substantially diminished; tracer oxygen profiles approached those expected for a completely recovered, flow-limited substance. At 37 degrees C, much larger tracer oxygen sequestration occurred. Experiments were carried out at each temperature at higher and lower hematocrit, and oxygen consumption at each temperature was found to be independent of hematocrit. The tissue space of distribution for tracer oxygen relative to the total sinusoidal vascular content was influenced by the hematocrit: it was smaller at higher hematocrit and larger at lower hematocrit, as expected. The derived partition coefficient of oxygen for liver cells relative to plasma (expressed in terms of the liver and plasma water spaces) was, on average, 2.62 ml/ml; it was independent of the hematocrit. Analysis of the indicator dilution experiments indicates that the tracer oxygen is distributed into tissue in a flow-limited rather than a barrier-limited fashion, and that with this, an ongoing concomitant intracellular sequestration of tracer can be seen. PMID- 1505921 TI - Inhibition of rat hepatic lipocyte activation in culture by interferon-gamma. AB - Hepatic lipocytes (perisinusoidal, Ito cells) are the primary matrix-producing cells in liver fibrosis. During liver injury they undergo activation, a process characterized by cell proliferation and increased fibrogenesis. We and others have established a culture model in which in vivo features of lipocyte activation can be mimicked by cells grown on plastic. Additionally, we recently showed that activation is associated with new expression of smooth muscle-specific alpha actin both in vivo and in culture. Although interferon-gamma is known to inhibit collagen production in some systems, its action as a general modulator of lipocyte activation has not been examined; this issue forms the basis for our study. In culture-activated lipocytes, interferon-gamma (1,000 U/ml) significantly inhibited lipocyte proliferation as assessed by [3H]thymidine incorporation assay and nuclear autoradiography. In time-course studies of activation, it also markedly reduced expression of smooth muscle-specific alpha actin and its messenger RNA. In dose-response experiments, maximal inhibitory effects on smooth muscle-specific alpha-actin mRNA gene expression were achieved with as little as 10 U interferon-gamma/ml. Inhibition of cellular activation was reversible; after interferon-gamma withdrawal, messenger RNA levels of smooth muscle-specific alpha-actin returned to untreated control levels. The effect of interferon-gamma extended to extracellular matrix gene expression, with reduction of type I collagen, type IV collagen and total fibronectin messenger RNAs to 3%, 24% and 15% of untreated control levels, respectively. In contrast to the marked effects on smooth muscle-specific alpha-actin and extracellular matrix gene expression, interferon-gamma reduced total protein synthesis by only 17.7%.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1505922 TI - Zinc supplementation reduces blood ammonia and increases liver ornithine transcarbamylase activity in experimental cirrhosis. AB - Zinc deficiency is common in cirrhosis and may be involved in the alteration of ammonia metabolism. Rats with carbon tetrachloride-induced cirrhosis have high plasma ammonia and low serum and tissue zinc levels. We used this model to examine the effects of oral zinc supplementation on activities of plasma ammonia and liver ornithine transcarbamylase (a key enzyme in the urea cycle). These parameters were examined in two consecutive experiments. Each experiment included two groups of rats treated with carbon tetrachloride; one group received zinc in the drinking water during the induction of cirrhosis, and another served as a control group. Regardless of zinc supplementation, all carbon tetrachloride treated rats exhibited similar micronodular cirrhosis, with similar histological appearance and liver function impairment. Cirrhotic rats without zinc supplementation showed high plasma ammonia and low serum and hepatic zinc levels and reduced liver ornithine transcarbamylase activity. Serum, hepatic zinc and liver ornithine transcarbamylase activity increased significantly in the zinc supplemented group, and these rats' plasma ammonia levels became normal. Plasma ammonia level was significantly inversely correlated with liver ornithine transcarbamylase activity and positively correlated with serum and hepatic zinc content. Our results suggest that zinc deficiency may modify hepatic ornithine transcarbamylase activity and, therefore, ammonia disposal. PMID- 1505923 TI - Fat-storing cells of the rat liver synthesize and secrete C1-esterase inhibitor; modulation by cytokines. AB - During liver fibrogenesis, fat-storing cells transform into myofibroblast-like cells and produce increasing amounts of extracellular matrix proteins. Because fat-storing cells produce alpha 2-macroglobulin, an important serine protease inhibitor (serpin), we investigated whether fat-storing cells also synthesize C1 esterase inhibitor, another important serpin. C1-esterase inhibitor synthesis was studied in rat fat-storing cells at day 0, 3 and 7 after isolation by biosynthetic labeling, immunoprecipitation and sodium dodecyl sulfate polyacrylamide gel electrophoresis. Messenger RNA was examined by Northern-blot analysis. C1-esterase inhibitor gene expression and synthesis were detectable in freshly isolated fat-storing cells and increased distinctly during the time in culture. The cellular source of C1-esterase inhibitor in fat-storing cell cultures was also identified by in situ hybridization of cells at different times after isolation. By inhibition of the N-glycosylation using tunicamycin, rat C1 esterase inhibitor was identified as a glycoprotein. The time course of C1 esterase inhibitor secretion was determined by pulse-chase experiments. C1 esterase inhibitor synthesis was increased 6-fold to 10-fold by interferon-gamma. Specific messenger RNA levels were also raised distinctly by this cytokine. In contrast, interferon-alpha and dexamethasone did not alter C1-esterase inhibitor gene expression. Because C1-esterase inhibitor synthesis is increased by advancing culture time and by the inflammatory mediator interferon-gamma, we suggest that fat-storing cells may enhance the deposition of extracellular matrix proteins by inhibiting their degradation. PMID- 1505925 TI - Redundant publication: deja vu all over again. PMID- 1505924 TI - Assessment of hepatic phagocytic activity by in vivo microscopy after liver transplantation in the rat. AB - Phagocytic activity of sinusoidal lining cells was studied in 32 livers of male Lewis rats by in vivo fluorescence microscopy with epiillumination. Normal livers (group 1, n = 8) were compared with orthotopic syngeneic liver grafts 90 min after reperfusion after a period of cold storage in University of Wisconsin solution for 17 hr (group 2, n = 10) or 24 hr (group 3, n = 14). After bolus injection of fluorescence-labeled latex particles (3 x 10(8)/kg; diameter = 1.1 micron), zonal distribution and kinetics of adherence of latex beads were quantified by off-line video analysis. Hepatocellular function was estimated by the rate of bile production and biliary concentrations of bile acids. In normal livers 50%, 37% and 13% of injected latex beads adhered in zones 1, 2 and 3, respectively, whereas in transplanted livers a more homogeneous distribution was found (group 2: 37%, 41%, 22%; group 3: 37%, 39%, 24%; p less than 0.01 vs. controls by analysis of variance). Kinetic analysis of phagocytic activity showed no significant difference between group 1 (88% adherence of visible latex beads 3 min after injection) and group 2 (90% adherence). However, after long-term preservation in group 3, sinusoidal adherence was significantly faster (96.4% adherence; p less than 0.001). Bile secretion in group 2 was lower than in controls and severely depressed in group 3 (group 1: 1.1 +/- 0.07 microliter/min/gm liver [mean +/- S.E.M.]; group 2: 0.8 +/- 0.07; group 3: 0.1 +/ 0.04; p less than 0.001) without significant changes in bile acid concentrations.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1505926 TI - Nutritional therapy for alcoholic hepatitis: are we there yet? PMID- 1505927 TI - Anesthesia and liver blood flow. PMID- 1505928 TI - T-cell lymphoma in Singapore: pathology, clinical findings and association with HTLV-1 antibodies. AB - Of 128 cases of malignant lymphomas studied in Singapore between 1986 and 1988, 28 were identified as peripheral T-cell lymphomas. Sera from two of the 128 cases were positive for HTLV-1 antibodies and both cases had the clinical and pathological features of adult T-cell leukaemia/lymphoma. The pathological and clinical features of the 28 cases of peripheral T-cell lymphoma are presented in detail. Survival data indicated no significant difference between the low grade and high grade histological types. Three of the patients had previous or concomitant malignancies. The percentage of T-cell lymphomas associated with HTLV 1 infection in Singapore is low compared to those areas in which HTLV-1 is endemic. PMID- 1505929 TI - Mucosal capillary thrombi in rectal biopsies. AB - We studied the initial rectal biopsy from 46 patients in whom subsequent follow up established the diagnosis of either self-limited colitis or inflammatory bowel disease. An additional 12 non-inflamed rectal biopsies were also studied. There was between 2 and 8 years of follow-up in each of these cases. Staining for fibrin (MSB, fibrinogen), platelets (factor XIIIA, Y2/51), and capillary basement membrane (reticulin, collagen 4) was performed to identify thrombotic material within capillaries. Mucosal capillary thrombi were best identified by staining for factor XIIIA; thrombi were observed in 8/13 cases of ulcerative colitis, 4/10 cases of Crohn's disease, 1/3 cases of unspecified inflammatory bowel disease and 5/20 cases of self-limited colitis. The presence of capillary thrombi was not related to the severity of inflammation, but none of the control biopsies showed capillary thrombi. Their presence seems of little diagnostic value in distinguishing inflammatory bowel disease from self-limited colitis. The pathogenetic significance of these mucosal capillary thrombi is uncertain. PMID- 1505930 TI - Urinary bladder carcinoma with a neoplastic squamous component: a mapping study of 31 cases. AB - A mapping study of cystectomy specimens in three cases of pure squamous cell carcinoma and 28 cases with transitional cell carcinoma with squamous differentiation is described, with an emphasis on the histogenesis of pure squamous cell carcinoma. Two of the three cases of pure squamous cell carcinoma had extensive benign keratinizing mucosa and an atypical squamous metaplastic mucosa contiguous with the tumour. These pure squamous cell carcinomas seemed to be derived from the squamous metaplasia. On the other hand, in all except one of the cases of transitional cell carcinoma with squamous differentiation, there was neither benign keratinizing nor atypical squamous metaplastic mucosa in the bladder. The quantitative amounts of both the transitional cell and squamous components differed from case to case in 28 cases with transitional cell carcinoma with squamous differentiation. Five of the 28 had a tumour composed predominantly of a squamous component with minute transitional cell components at the margin. In another two cases, transitional carcinoma in situ or satellite tumours of transitional cells were present adjacent to the main tumour which was composed of squamous cell carcinoma alone. We think these seven tumours originated as a result of extensive squamous differentiation in the transitional cell carcinomas. These features may indicate two forms of histogenesis of pure squamous cell carcinoma. The first is malignant transformation on the basis of squamous metaplasia of the bladder mucosa and the second is extensive squamous differentiation in a pre-existing transitional cell carcinoma. PMID- 1505931 TI - Localized amyloidosis of the lower genitourinary tract: a clinicopathological and immunohistochemical study of nine cases. AB - A series of nine cases of localized amyloidosis of the lower genitourinary tract are reported. The patients comprised six males and three females with an age range of 50-79 years at initial presentation. Clinically and on cystoscopy, the lesions were often diagnosed as neoplasms. Histologically, seven cases had typical features of localized amyloid deposits, while two cases had an unusual appearance with a florid histiocytic and giant cell reaction. Using an immunoperoxidase staining method the deposits were non-reactive with antibodies to serum amyloid A protein, prealbumin and beta 2 microglobulin, while equivocal immunoreactivity was seen with anti-light chain antibodies. PMID- 1505932 TI - Metastatic prostatic carcinoma presenting as left-sided cervical lymphadenopathy: a series of 11 cases. AB - Eleven cases of metastatic prostatic carcinoma in cervical lymph nodes as a primary presenting sign were identified in a survey of 250 cervical lymph node biopsies from men. The diagnosis was clinically unsuspected in all cases. All occurred on the left side of the neck. These 11 cases represented 11% of all metastatic carcinomas in the neck and 20% of those with left-sided involvement. The diagnosis was readily confirmed by immunostaining for prostate specific antigen and prostate specific acid phosphatase. Six patients are alive and well at an average of 25.8 months and five others survived for an average of 34.4 months, the combined survival being 29.7 months. This contrasts with the dismal fate of patients with metastatic adenocarcinoma from other sites who all died at an average of 2 months from diagnosis. Prostatic carcinoma should always be considered in the differential diagnosis of metastatic carcinoma in cervical lymph nodes in elderly men, as appropriate treatment results in worthwhile prolongation of life. PMID- 1505934 TI - Malignant Warthin's tumour: a case study. AB - Malignant transformation of a benign Warthin's tumour (adenolymphoma) is extremely rare. The light microscopic and ultrastructural features of an adenocarcinoma arising in a Warthin's tumour in the parotid gland are described. Light microscopy demonstrated a transition zone from the benign to the malignant component, and the malignant cells revealed oncocytic features by both light- and electronmicroscopy. PMID- 1505935 TI - Metastatic small cell melanoma to the stomach mimicking primary gastric lymphoma. PMID- 1505933 TI - Collecting duct carcinoma: cytogenetic characterization. AB - Most renal cell carcinomas are assigned to either the papillary or clear cell, non-papillary type by morphological and cytogenetic criteria. In rare cases, papillary carcinomas of the kidney have been classified as collecting duct carcinoma because of their medullary localization and the associated hyperplastic and dysplastic epithelial lesions of collecting ducts in the vicinity of the tumour. In this first report on the cytogenetics of collecting duct carcinoma, we describe unique and consistent chromosomal aberrations in three cases. Each of the three tumours showed monosomies for chromosomes 1, 6, 14, 15, and 22. This suggests that collecting duct carcinoma is the third type of kidney tumour whose definition is based on morphological as well as on cytogenetic criteria. It appears to be cytogenetically different from the cortical papillary kidney tumour which exhibits trisomy 17 and tri- or tetrasomy 7, and from the non-papillary renal cell carcinoma which characteristically presents deletion of the short arm of chromosome 3. PMID- 1505936 TI - Intrapulmonary thymoma. PMID- 1505937 TI - Bladder xanthoma. PMID- 1505938 TI - Angiosarcoma complicating xeroderma pigmentosum. PMID- 1505939 TI - Dermatofibrosarcoma protuberans recurring as a giant cell fibroblastoma. PMID- 1505940 TI - Focal lymphoid hyperplasia of the oesophagus: report of a case. PMID- 1505941 TI - The leucocyte protein L1 (calprotectin): usefulness as an immunohistochemical marker antigen and putative biological function. PMID- 1505942 TI - Evaluation of a cosmid contig physical map of human chromosome 16. AB - A cosmid contig physical map of human chromosome 16 has been developed by repetitive sequence finger-printing of approximately 4000 cosmid clones obtained from a chromosome 16-specific cosmid library. The arrangement of clones in contigs is determined by (1) estimating cosmid length and determining the likelihoods for all possible pairwise clone overlaps, using the fingerprint data, and (2) using an optimization technique to fit contig maps to these estimates. Two important questions concerning this contig map are how much of chromosome 16 is covered and how accurate are the assembled contigs. Both questions can be addressed by hybridization of single-copy sequence probes to gridded arrays of the cosmids. All of the fingerprinted clones have been arrayed on nylon membranes so that any region of interest can be identified by hybridization. The hybridization experiments indicate that approximately 84% of the euchromatic arms of chromosome 16 are covered by contigs and singleton cosmids. Both grid hybridization (26 contigs) and pulsed-field gel electrophoresis experiments (11 contigs) confirmed the assembled contigs, indicating that false positive overlaps occur infrequently in the present map. Furthermore, regional localization of 93 contigs and singleton cosmids to a somatic cell hybrid mapping panel indicates that there is no bias in the coverage of the euchromatic arms. PMID- 1505943 TI - Base compositional structure of genomes. AB - We model the base compositional structure of the human and Escherichia coli genomes. Three particular properties are first quantified: (1) There is a significant tendency for any region of either genome to have a strand-symmetric base composition. (2) The variation in base composition from region to region, within each genome, is very much larger than expected from common homogeneous stochastic models. (3) A given local base composition tends to persist over a scale of at least kilobases (E. coli) or tens of kilobases (human). Multidomain stochastic models from the literature are reviewed and sharpened. In particular, quantitative measurements of the third property lead us to suggest a significant shift in the style of domain models, in which the variation of A+T content with position is modeled by a random walk with frequent small steps rather than with large quantum jumps. As an application, we suggest a way to reduce the amount of computation in the assembly of large sequences from sequences of randomly chosen fragments. PMID- 1505944 TI - MEPS parameters and graph analysis for the use of recombination to construct ordered sets of overlapping clones. AB - Homologous recombination can provide a basis for the construction of an ordered set of overlapping clones. The principle is to make two libraries, each in a vector that has a different selectable marker flanking the insert site. Recombination between the flanking markers, leading to a selectable phenotype, can only occur as the consequence of crossing over between inserts. The two libraries are crossed in a matrix, allowing the construction of an ordered set. The logic, akin to S. Benzer's (1961, Genetics 47:403-415) for the arrangement of deletion and point mutations, has a graph theoretic formulation, which helps to cope with the complex and noisy data inherent in the physical mapping of genomes rich in repeated sequences. The minimum length of identity required for homologous recombination is called the MEPS (minimum efficient processing segment) and is a property of each recombination pathway. The amount and the type of sequence similarity required for two sequences to recombine is different from that implied by either the conservation of restriction sites or by most procedures of hybridization. PMID- 1505946 TI - CpG islands as gene markers in the human genome. AB - CpG islands are short, dispersed regions of unmethylated DNA with a high frequency of CpG dinucleotides relative to the bulk genome. We have analyzed 375 genes and 58 pseudogenes from the human entries in the EMBL Database for the presence of CpG islands. All 240 islands identified are associated with genes, and almost all cover at least a part of one exon; i.e., they are useful landmarks in the genome for identifying genes. More than half of the genes analyzed were associated with islands. All housekeeping and widely expressed genes have a CpG island covering the transcription start, whereas 40% of the genes with a tissue specific or limited expression are associated with islands. In this latter group of genes, the position of the islands was not biased toward the 5' end of the transcription unit. PMID- 1505945 TI - Assignment of a human DNA double-strand break repair gene (XRCC5) to chromosome 2. AB - The Chinese hamster ovary (CHO-K1) cell mutant XRS-6 is defective in rejoining of DNA double-strand breaks and is hypersensitive to X-rays, gamma-rays, and bleomycin. Radiation resistance or sensitivity of somatic cell hybrids constructed from the fusion of XRS-6 cells with primary human fibroblasts strongly correlated with the retention of human chromosome 2 isozyme and molecular markers. Discordancies between some chromosome 2 markers and the radiation resistance phenotype in some of the hybrid cells suggested the location of the X-ray repair cross complementing 5 (XRCC5) gene on the p arm of chromosome 2. Introduction of human chromosome 2 by microcell-mediated chromosome transfer into the radiation-sensitive XRS-6 cells resulted in hybrid cells in which the radiation sensitivity was complemented. The chromosome 2p origin of the complementing human DNA in the microcell hybrids was supported by fluorescent in situ hybridization analysis of human metaphases using human DNA amplified from the hybrids by inter-Alu-PCR as chromosome-painting probes. XRCC5 is therefore provisionally assigned to human chromosome 2p. PMID- 1505947 TI - The evolution of human chromosome 21: evidence from in situ hybridization in marsupials and a monotreme. AB - We have mapped five human chromosome 21 (HSA 21) markers in marsupials and a monotreme, two major groups of mammals that diverged from eutherians 130-150 and 150-170 million years before present (MYrBP), respectively. We have found that these genes map to two distinct autosomal sites, one containing SOD1/CBR/BCEI and the other containing ETS2/INFAR, in the marsupials Macropus eugenii and Sminthopsis macroura (which belong to orders that diverged 40-80 MYrBP), as well as in the monotreme Ornithorhynchus anatinus (the platypus). Since marsupials and monotremes diverged independently from eutherians, these data suggest that HSA 21 genes were originally located in two separate autosomal blocks. In another Sminthopsis species, SOD1 is linked to TRF (a marker on HSA 3q), suggesting that the ancestral SOD1/CBR/BCEI region also included HSA 3 markers. We suggest that these blocks became fused early in the eutherian evolution to form a HSA 3/21 chromosome, which has remained intact in artiodactyls, but has been independently disrupted in both the primate and rodent lineages. PMID- 1505948 TI - Alpha satellite DNAs on chromosomes 10 and 12 are both members of the dimeric suprachromosomal subfamily, but display little identity at the nucleotide sequence level. AB - We have investigated the organization and complexity of alpha satellite DNA on chromosomes 10 and 12 by restriction endonuclease mapping, in situ hybridization (ISH), and DNA-sequencing methods. Alpha satellite DNA on both chromosomes displays a basic dimeric organization, revealed as a 6- and an 8-mer higher-order repeat (HOR) unit on chromosome 10 and as an 8-mer HOR on chromosome 12. While these HORs show complete chromosome specificity under high-stringency ISH conditions, they recognize an identical set of chromosomes under lower stringencies. At the nucleotide sequence level, both chromosome 10 HORs are 50% identical to the HOR on chromosome 12 and to all other alpha satellite DNA sequences from the in situ cross-hybridizing chromosomes, with the exception of chromosome 6. An 80% identity between chromosome 6- and chromosome 10-derived alphoid sequences was observed. These data suggest that the alphoid DNA on chromosomes 6 and 10 may represent a distinct subclass of the dimeric subfamily. These sequences are proposed to be present, along with the more typical dimeric alpha satellite sequences, on a number of different human chromosomes. PMID- 1505949 TI - Localization of the t(2;13) breakpoint of alveolar rhabdomyosarcoma on a physical map of chromosome 2. AB - A characteristic translocation t(2;13)(q35;q14) has been previously identified in the pediatric soft tissue tumor alveolar rhabdomyosarcoma. We have assembled a panel of lymphoblast, fibroblast, and somatic cell hybrid cell lines with deletions and unbalanced translocations involving chromosome 2 to develop a physical map of the distal 2q region. Twenty-two probes were localized on this physical map by Southern blot analysis of the mapping panel. The position of these probes with respect to the t(2;13) rhabdomyosarcoma breakpoint was then determined by quantitative Southern blot analysis of an alveolar rhabdomyosarcoma cell line with two copies of the derivative chromosome 13 and one copy of the derivative chromosome 2 and by analysis of somatic cell hybrid clones derived from an alveolar rhabdomyosarcoma cell line. We demonstrate that the t(2;13) breakpoint is situated within a map interval delimited by the distal deletion breakpoint in fibroblast line GM09892 and the t(X;2) breakpoint in somatic cell hybrid GM11022. Furthermore, from a comparison of our data with the linkage map of the syntenic region on mouse chromosome 1, we conclude that the t(2;13) breakpoint is most closely flanked by loci INHA and ALPI within this map interval. PMID- 1505950 TI - Chromosome mapping of the owl monkey CSF1R and IL5 genes. AB - We mapped the owl monkey colony-stimulating factor 1 receptor (CSF1R) locus to the proximal region of chromosome 3q of karyotype VI(K-VI) and karyotype V(K-V) and the interleukin 5 (IL5) locus to the mid-region of chromosome 3q(K-VI) and 19q(K-IV) using a combination of Southern hybridization of somatic cells and in situ chromosomal hybridization methodologies. The findings support the proposed evolution of owl monkey chromosome 3(K-VI) from a fusion of two smaller structures, the homologs of chromosomes 6 and 19 (K-IV). The data also indicate genomic conservation of the HSA 5q23-q35 segment in the higher primates. PMID- 1505951 TI - High-resolution cytogenetic-based physical map of human chromosome 16. AB - A panel of 54 mouse/human somatic cell hybrids, each possessing various portions of chromosome 16, was constructed; 46 were constructed from naturally occurring rearrangements of this chromosome, which were ascertained in clinical cytogenetics laboratories, and a further 8 from rearrangements spontaneously arising during tissue culture. By mapping 235 DNA markers to this panel of hybrids, and in relation to four fragile sites and the centromere, a cytogenetic based physical map of chromosome 16 with an average resolution of 1.6 Mb was generated. Included are 66 DNA markers that have been typed in the CEPH pedigrees, and these will allow the construction of a detailed correlation of the cytogenetic-based physical map and the genetic map of this chromosome. Cosmids from chromosome 16 that have been assembled into contigs by use of repetitive sequence fingerprinting have been mapped to the hybrid panel. Approximately 11% of the euchromatin is now both represented in such contigs and located on the cytogenetic-based physical map. This high-resolution cytogenetic-based physical map of chromosome 16 will provide the basis for the cloning of genetically mapped disease genes, genes disrupted in cytogenetic rearrangements that have produced abnormal phenotypes, and cancer breakpoints. PMID- 1505952 TI - The amplified long genomic sequence (ALGS) located in the centromeric regions of mouse chromosomes. AB - We reported previously that the haploid genome of standard strains of laboratory mice contains approximately 70 copies of an amplified long genomic sequence, designated ALGS, that includes a retroposon of the gene for elongation factor 2 (MER). The length of each repeating unit is more than 60 kb, and the sequence of the unit is highly conserved among the repeats. In the present study, Southern blot analysis of the genomes of wild rodents demonstrated that the ALGS is present in all subspecies of Mus musculus and is abundant in M. spicilegus, whereas it is absent in M. spretus as well as in Rattus and other closely related genera. This result indicates that the amplification occurred after the species differentiation with the genus Mus and at least prior to the differentiation of subspecies of M. musculus. To locate chromosomal positions of the ALGS, in situ hybridization was carried out with laboratory strains and wild mice. It appears that the ALGS is located in the centromeric regions of most chromosomes in laboratory mice, M. musculus and M. spicilegus, whereas no positive signals were observed with M. spretus, in accordance with the results from the Southern blotting analysis. PMID- 1505953 TI - Nucleotide sequence analysis of 95 kb near the 3' end of the murine T-cell receptor alpha/delta chain locus: strategy and methodology. AB - The nucleotide sequence of a region at the 3' terminus of the murine T-cell receptor alpha/delta chain locus is presented. This region, which encodes the constant region genes for alpha and delta chain polypeptides and all 50 joining gene segments for the alpha chain polypeptide, spans 94,647 bp and includes more than 50 noncoding sequence elements important for T-cell receptor gene rearrangement and expression. DNA sequencing of this region included complete analysis of two cosmid clones and five additional restriction fragments using a random subcloning approach with various manual and automated sequencing strategies. The automated sequencing strategies hold considerable promise for future large-scale DNA sequencing efforts. PMID- 1505954 TI - Organization, structure, and function of 95 kb of DNA spanning the murine T-cell receptor C alpha/C delta region. AB - We have analyzed the organization, structure, and function of the murine T-cell receptor C alpha/C delta region. This region spans 94.6 kb of DNA and contains the C alpha and C delta genes, as well as the V delta 5, J delta 2, and 50 different J alpha gene segments. Within this sequence we have identified 15 new J alpha gene segments, 40 new 5' RNA splice signals, and 40 new DNA rearrangement signals for the J alpha gene segments. The murine C alpha/C delta sequence contains an exceptionally high level of coding sequence with over 5.7% of the total sequence found in the exons. This is much more than that found in the beta globin locus and the HPRT locus. Using the sequence data obtained from the C alpha/C delta region, we have designed simple assays to test for J alpha gene segment transcription and to determine the level of polymorphism for simple repeat sequences among different inbred strains of mice using the polymerase chain reaction. Furthermore, comparisons of this 95 kb of sequence with the available sequence from homologous regions of other species have led to the identification of a highly conserved sequence that is present throughout vertebrates and in the mouse binds lymphocyte-specific nuclear proteins. Comparisons of a 10-kb region, which includes the C alpha gene in human and mouse, average 66% sequence similarity. These studies support the contention that large-scale DNA sequencing projects of homologous regions of mouse and human will provide powerful new tools for studying the biology and evolution of loci such as the T-cell receptor and for identifying and posing new questions about the functions of conserved sequences. PMID- 1505955 TI - Isolation of a zinc finger motif (ZNF75) mapping on chromosome Xq26. AB - We report here the partial characterization of a new human zinc finger (ZNF75) gene of the Kruppel type mapping to the long arm of the X chromosome. A cosmid clone was isolated from a library specific to the Xq24-qter region by hybridization to a degenerate oligonucleotide representing the link between two contigous fingers of the C2H2 type. The sequence of the pertinent cosmid fragments demonstrated five consecutive zinc finger motifs, all pertaining to the Kruppel family. A reading frame starting at least 75 amino acids before the first zinc finger and ending 11 amino acids after the last one was identified; comparison with other ZF genes suggests that this genomic fragment represents the carboxy-terminal exon of the gene. Homology of approximately 55% in the zinc finger region was detected with many zinc finger genes including mouse Zfp-35 and human ZFN7 cDNA clones. Mapping using a panel of sematic cell hybrids and chromosomal in situ hybridization localized the gene to Xq26, in a region not previously known to contain zinc finger genes. PMID- 1505956 TI - Strategy for detecting cellular transcripts promoted by human endogenous long terminal repeats: identification of a novel gene (CDC4L) with homology to yeast CDC4. AB - Several families of repetitive sequences related to integrated retroviruses have been identified in the human genome. The largest of these families, the RTVL-H family, has close to 1000 members in addition to a similar number of solitary long terminal repeats (LTRs) dispersed on all chromosomes. Previous work has shown that the expression of genomic RTVL-H elements is driven by their LTRs and that some LTRs can promote expression of a reporter gene. These observations suggest that some endogenous RTVL-HLTRs may naturally regulate the transcription of adjacent cellular genes or that rearrangements involving these elements may cause aberrant gene expression. To investigate this possibility, we have used a differential screening strategy to identify chimeric cDNA clones derived from LTR promoted transcripts. Here we report the identification and analysis of four such clones isolated from an NTera2D1 (teratocarcinoma) cDNA library. Two of the clones, AF-1 and AF-2, contain termination codons in all reading frames. Another clone, AF-4, contains LTR sequences linked in the genome to a CpG island. The fourth clone, AF-3, contains an 862-bp open reading frame representing part of a novel gene (CDC4L) with homology to the yeast cell division cycle gene CDC4. These findings indicate that RTVL-H elements may be involved in the regulation of diverse cellular transcripts in human cells. PMID- 1505957 TI - Deletion mapping of H-Y antigen to the long arm of the human Y chromosome. AB - A gene encoding or controlling the expression of the H-Y transplantation antigen was previously mapped to the human Y chromosome. We now report the sublocalization of this gene on the long arm of the human Y chromosome. Eight patients with Y-chromosomal abnormalities were examined with a series of existing and new DNA markers for the Y chromosome. The resulting deletion map was correlated with H-Y antigen expression. We conclude that the H-Y antigen gene maps to a portion of deletion interval 6 that is identified by specific DNA markers. PMID- 1505958 TI - Sequences from a family of bovine Y-chromosomal repeats. AB - A 307-bp Sau3AI fragment previously cloned by deletion enrichment from the bovine Y chromosome was used to isolate a larger lambda EMBL3A genomic cattle clone. The whole 13-kb insert did not give a sex-specific pattern of hybridization to Southern blots of cattle DNA. Subclones from this phage, however, did show that this fragment had a Y-chromosomal origin. It was estimated that at least 40% of the cattle Y chromosome is composed of repeated sequences related to those within these subcloned fragments. Sequences within these subclones are male-specific or male-enriched also in sheep, goats, and deer. Comparison of cattle and sheep homologues of these sequences reveals that much greater amplification and rearrangement have occurred on the cattle Y chromosome than on the sheep Y. The apparent insertion of sequences into cattle Y-specific sequences relative to the sheep homologues suggests possible mechanisms for the evolution of the artiodactyl Y chromosome. PMID- 1505959 TI - Human perforin (PRF1) maps to 10q22, a region that is syntenic with mouse chromosome 10. AB - Perforin (PRF1) is a cytolytic, channel-forming protein of cytolytic T cells, natural killer cells, and granulated metrial gland cells and plays a crucial role in the killer cell-mediated elimination of virally infected host cells, tumor cells, and allotransplants. Two-thirds of the perforin sequence is homologous to the lytic, channel-forming complement proteins C6, C7, C8 alpha, C8 beta, and C9. Using cosmid DNA containing the PRF1 gene as a probe for fluorescence in situ hybridization, we have reevaluated its chromosomal location. Previously assigned to chromosome 17q11-q21, it has now been mapped to 10q22. The human PRF1 locus lies within a conserved synteny segment present on mouse chromosome 10, consistent with the previous chromosomal assignment of mouse perforin. The perforin locus is not linked to any of the genes of the terminal complement system. PMID- 1505960 TI - The genes for MHC class II regulatory factors RFX1 and RFX2 are located on the short arm of chromosome 19. AB - RFX1 is a transacting DNA-binding regulatory factor involved in the control of MHC class II gene expression. RFX2 is a structurally very similar protein with identical DNA binding features. A member of the family of RFX factors is affected in an autosomal recessive disease, MHC class II deficient combined immunodeficiency (CID), caused by a defect in a trans-acting regulatory factor controlling MHC class II gene expression. In situ hybridization with 3H-labeled RFX1 cDNA has allowed us to identify two distinct targets on the short arm of chromosome 19 (19p13.1 and 19p13.2-p13.3). With the use of biotinylated genomic cosmid clones specific for RFX1 and RFX2, respectively, it was then possible to localize RFX1 at 19p13.1 and RFX2 at 19p13.2-p13.3. These two regulatory genes are thus assigned to a region of high gene density and RFX1 is close to another DNA-binding factor, LYL1. PMID- 1505961 TI - Structure and sequence of the human alpha-L-iduronidase gene. AB - In humans, a deficiency of the lysosomal hydrolase alpha-L-iduronidase (IDUA;EC 3.2.1.76) results in the lysosomal storage of the glycosaminoglycans heparan sulfate and dermatan sulfate, thereby causing the lysosomal storage disorder mucopolysaccharidosis type I. The gene for IDUA is split into 14 exons spanning approximately 19 kb. We report the sequence of two non-contiguous segments of the IDUA gene, one 1.8-kb segment containing exons 1 and 2 and surrounding sequences and a second segment of 4.5 kb containing the last 12 exons. The potential promoter for IDUA has only GC box type consensus sequences consistent with a housekeeping promoter and is bounded by an Alu repeat sequence. The first two exons of IDUA are separated by an intron of 566 bp, then there is a large intron of approximately 13 kb, and the last 12 exons are clustered within 4.5 kb. No consensus polyadenylation signal was found in the 3' untranslated region, although two variant polyadenylation signals are proposed. PMID- 1505962 TI - A (CA)n repeat polymorphism for the human skeletal muscle alpha-actinin gene ACTN2 and its localization on the linkage map of chromosome 1. AB - A CA dinucleotide repeat polymorphism has been identified for the skeletal muscle alpha-actinin gene ACTN2. The observed heterozygosity is 44% (predicted heterozygosity 50%, PIC 0.47). This polymorphic marker has been localized between D1S74 and D1S103 on the multipoint linkage map of chromosome 1 at a position 44.4 cM from the most distal marker D1S68 at 1 qter. PMID- 1505963 TI - NF1-related locus on chromosome 15. AB - A neurofibromatosis type I (NF1)-related locus has been identified on chromosome 15. It contains a partial copy of the NF1 GAP-related domain, which is known to interact with the ras protooncogenes. However, the chromosome 15 sequence contains multiple deletions resulting in frameshift mutations and stop codons in several highly conserved sequence blocks. The locus on chromosome 15 therefore represents an NF1 pseudogene. This nonprocessed NF1 pseudogene may produce additional fragments in Southern blotting, pulsed-field gel, and PCR experiments with some NF1 cDNA probes or oligonucleotides. In addition, certain regions of the NF1 gene also cross-hybridize with a locus on chromosome 14. These loci must be considered in mutation analysis of patients with NF1 since aberrant findings may not always reflect changes in the NF1 gene. PMID- 1505964 TI - A heterozygous 4-bp deletion mutation in the Gs alpha gene (GNAS1) in a patient with Albright hereditary osteodystrophy. AB - Several heterozygous mutations within the gene encoding the alpha-subunit of Gs (GNAS1), the G protein that stimulates adenylyl cyclase, have been previously identified in patients with Albright hereditary osteodystrophy (AHO). We have now identified a fourth GNAS1 mutation from an AHO patient. Amplification by the polymerase chain reaction (PCR) of a genomic fragment encompassing GNAS1 exons 7 and 8 from one patient resulted in a product with aberrant migration on nondenaturing polyacrylamide and agarose gels. Direct DNA sequencing identified a 4-bp deletion in one allele of exon 7 encoding a frameshift with a premature stop codon. Analysis of lymphocyte RNA by reverse transcription-PCR and direct sequencing showed that the GNAS1 allele bearing the mutation is not expressed as mRNA. Consistent with this, Northern analysis revealed an approximate 50% deficiency in steady-state levels of GNAS1 mRNA. These findings further illustrate the heterogeneity of GNAS1 gene defects in AHO. PMID- 1505965 TI - A method for the rapid sequence-independent amplification of microdissected chromosomal material. AB - We have developed a simple, efficient method by which microdissected material can be amplified directly in the collection container in a few hours. The procedure involves two initial rounds of DNA synthesis with T7 DNA polymerase, using a primer that contains a random pentanucleotide sequence at its 3' end and a defined sequence at its 5' end, followed by PCR amplification with the defined sequence as the primer. The resulting products can be biotinylated and used for fluorescence in situ hybridization (FISH) to confirm their chromosomal location. As few as 17 dissected chromosomal regions provide sufficient material for a specific FISH signal on the appropriate band of metaphase chromosomes. We have obtained a chromosome 6q25-qter-specific painting probe in this way. PMID- 1505966 TI - The gene encoding the human spasmolytic protein (SML1/hSP) is in 21q 22.3, physically linked to the homologous breast cancer marker gene BCEI/pS2. AB - The human spasmolytic protein, SML1/hSP, an inhibitor of spasmolytic activity and gastric acid secretion in the pig, has been shown to exhibit homology to the pS2 protein, an estrogen-dependent breast cancer marker. Moreover, SML1/hSP and pS2 are expressed at the same localization in the normal stomach and during healing of the gastrointestinal tract. Here we report the chromosomal localization, obtained by in situ hybridization, of the hSP gene (SML1) to chromosome 21 at 21q22.3. Using pulsed-field gel electrophoresis, we found SML1 to be within 230 kb of the BCEI/pS2 gene. PMID- 1505967 TI - The human BDNF gene maps between FSHB and HVBS1 at the boundary of 11p13-p14. AB - To map in detail the human gene for brain derived neurotrophic factor (BDNF) we have used a PCR-based assay to amplify the gene from somatic cell hybrids containing human chromosome 11 with deletion or translocation breakpoints in the WAGR region. The BDNF gene maps between the FSHB and HVBS1 loci, an interval of approximately 4 Mb at the boundary of 11p13 and 11p14. PMID- 1505968 TI - Evidence that nucleotide sequence identity is a requirement for meiotic crossing over within the mouse Eb recombinational hot spot. AB - Meiotic recombination in the mouse is sometimes restricted to specific chromosomal sites. For example, when recombinants within the I region of the mouse major histocompatibility complex (MHC) are examined, the breakpoints between standard alleles can usually be mapped to the Eb gene. DNA sequence analysis of five cases of meiotic crossing over associated with this gene suggests that the recombinational hot spot may be confined to large regions of nucleotide identity located within the second intron of the Eb gene. PMID- 1505969 TI - Assignment of the human homologue of the mouse t-complex gene TCTE3 to human chromosome 6q27. AB - The gene TCTE3 from the mouse t-complex region is expressed specifically in testicular germ cells. It maps in the central subregion of the t-complex on mouse chromosome 17 containing loci involved in transmission ratio distortion and male sterility. In this study, somatic cell hybrid lines have been used to map the human homologue, TCTE3, to the long arm of chromosome 6. CISS hybridization with the human lambda clone h117 refined this chromosome assignment to the very distal position of chromosome 6q27, thus providing further evidence that loci from the t complex of mouse chromosome 17 can map to opposite arms of human chromosome 6. PMID- 1505970 TI - In situ mapping of the gene coding for a leucine zipper DNA binding protein (CDR62) to 16p12-16p13.1. AB - A cDNA clone encoding the major antigen (CDR62) associated with the antibody induced paraneoplastic cerebellar degeneration has been used to identify the chromosomal location of the corresponding structural gene(s) by screening for its retention in a panel of rodent-human somatic cell hybrids. Having established the synteny of the gene with the autosome 16, we proceeded to its precise subregional mapping by in situ fluorescence hybridization with a recombinant lambda phage containing the genomic region homologous to the cDNA gene. The latter studies pin pointed the chromosomal localization of the structural CDR62 gene within the interval 16p12-16p13.1. PMID- 1505971 TI - In situ mapping of the chicken progesterone receptor gene and the ovalbumin gene. AB - The chicken progesterone receptor (cPR) gene and the ovalbumin (OA) gene, a target of cPR regulation, have been mapped via fluorescent in situ hybridization to the two largest chromosomes of the chicken karyotype. cPR is subtelomeric on the long arm of chromosome 1 and OA is on the long arm of chromosome 2, close to the centromere. A 35-kb cosmid probe for the cPR gene and two genomic fragments of 9.2 and 15 kb for the OA gene were biotin-labeled for nonradioactive localization of the two chicken loci. PMID- 1505972 TI - Sequence analysis of a full-length cDNA for the murine pro alpha 2(I) collagen chain: comparison of the derived primary structure with human pro alpha 2(I) collagen. AB - Comparison of the nucleotide sequence and primary structure of murine and human pro alpha 2(I) collagen indicates a high degree of homology: 87% at the nucleotide level and 87% at the amino acid level, with the greatest degree of variability in the amino- and carboxy-pro-peptide domains. The homology is greatest in the triple helical domain, repeating [Gly-X-Y]338, exhibiting 90% homology at the amino acid level, with only X and Y position residue substitutions. The X and Y residues show 86% homology between murine and human pro alpha 2(I) collagen triple helices, with no truly nonconservative substitutions. PMID- 1505973 TI - Complementary physical and genetic techniques map the vinculin (VCL) gene on chromosome 10q. AB - Vinculin is a cytoskeletal protein component of adherens type cell junctions. The gene had been mapped to 10q11.2-qter. We have used a combination of physical and genetic mapping techniques to refine this localization. Hybridization of the vinculin cDNA probe, HV1, to a human-rodent somatic hybrid panel initially suggested a position of either 10q11.2 or 10q22.1-10q23. Genetic recombination mapping in three-generation families with multiple endocrine neoplasia type 2 (MEN2) indicated a position distal to D10S22 (10q21.1) in 10q22.1-10q23. This was confirmed by hybridization of the vinculin cDNA to flow-sorted translocation derivative chromosomes containing the q21-qter portion of chromosome 10. We conclude that the vinculin locus maps in 10q22.1-q23, distal to D10S22. PMID- 1505974 TI - Identification and purification of overlapping cosmid clones of the region Xq24 qter of human X chromosome using HPLC. AB - The assembly of a large physical map of genomes requires simultaneous analysis of many cosmid clones for overlapping regions. The search for overlapping regions may be achieved by various means. High-performance liquid chromatography (HPLC) provides an alternative to gel electrophoresis since microgram amounts of each DNA fragment may be collected into individual test tubes for further analysis. HPLC has been used to identify overlapping cosmid clones from a pool of cosmid DNA containing the terminal portion of the long arm of the human X chromosome (Xq24-qter). Among 400 cosmids analyzed, 3 were shown to overlap. PMID- 1505975 TI - De novo splice site mutation in the antithrombin III (AT3) gene causing recurrent venous thrombosis: demonstration of exon skipping by ectopic transcript analysis. AB - A single basepair substitution at conserved position -1 in the exon 3a donor splice site of the liver-expressed antithrombin III (AT3) gene was detected by PCR/direct sequencing in a patient with sporadic type 1 ATIII deficiency and recurrent venous thrombosis. The lesion, a heterozygous silent AAG----AAA transition at Lys 176 occurred de novo in the proposita. Ectopic transcript analysis of lymphocyte mRNA demonstrated the presence of an abnormally sized mRNA specific to the patient which was shown by cDNA sequencing to lack exon 3a. Oligonucleotide discriminant hybridization demonstrated the absence of any detectable transcript of normal length derived from the disease allele. These findings demonstrate the utility of ectopic transcript analysis in the characterization of defects of mRNA splicing. PMID- 1505976 TI - D21S215 is a (GT)n polymorphic marker close to centromeric alphoid sequences on chromosome 21. AB - A plasmid, AWZ1, that contained a dinucleotide (GT)n repeat was identified from a chromosome 21-specific genomic library. When amplified by PCR from human genomic DNA, the repeat length was highly polymorphic between individuals; its location, D21S215, was mapped in the CEPH pedigrees by linkage analysis to the pericentromeric region of chromosome 21. It is the closest polymorphic marker to alphoid sequences on this chromosome. PMID- 1505977 TI - Confirmation of linkage of limb-girdle muscular dystrophy, type 2, to chromosome 15. PMID- 1505978 TI - Localization of the human kinesin-related gene to band 10q24 by fluorescence in situ hybridization. PMID- 1505979 TI - Assignment of the human slow skeletal troponin T gene to 19q13.4 using somatic cell hybrids and fluorescence in situ hybridization analysis. PMID- 1505980 TI - Report on the sequencing by hybridization workshop. PMID- 1505981 TI - A DNA methylation imprint, determined by the sex of the parent, distinguishes the Angelman and Prader-Willi syndromes. AB - The Angelman (AS) and Prader-Willi (PWS) syndromes are two clinically distinct disorders that are caused by a differential parental origin of chromosome 15q11 q13 deletions. Both also can result from uniparental disomy (the inheritance of both copies of chromosome 15 from only one parent). Loss of the paternal copy of 15q11-q13, whether by deletion or maternal uniparental disomy, leads to PWS, whereas a maternal deletion or paternal uniparental disomy leads to AS. The differential modification in expression of certain mammalian genes dependent upon parental origin is known as genomic imprinting, and AS and PWS represent the best examples of this phenomenon in humans. Although the molecular mechanisms of genomic imprinting are unknown, DNA methylation has been postulated to play a role in the imprinting process. Using restriction digests with the methyl sensitive enzymes HpaII and HhaI and probing Southern blots with several genomic and cDNA probes, we have systematically scanned segments of 15q11-q13 for DNA methylation differences between patients with PWS (20 deletion, 20 uniparental disomy) and those with AS (26 deletion, 1 uniparental disomy). The highly evolutionarily conserved cDNA, DN34, identifies distinct differences in DNA methylation of the parental alleles at the D15S9 locus. Thus, DNA methylation may be used as a reliable, postnatal diagnostic tool in these syndromes. Furthermore, our findings demonstrate the first known epigenetic event, dependent on the sex of the parent, for a locus within 15q11-q13. We propose that expression of the gene detected by DN34 is regulated by genomic imprinting and, therefore, that it is a candidate gene for PWS and/or AS. PMID- 1505982 TI - Resolution of the two loci for autosomal dominant aniridia, AN1 and AN2, to a single locus on chromosome 11p13. AB - Two distinct loci have been proposed for aniridia; AN1 for autosomal dominant aniridia on chromosome 2p and AN2 for the aniridia in the WAGR contiguous gene syndrome on chromosome 11p13. In this report, the kindred segregating for autosomal dominant aniridia, which suggested linkage to acid phosphatase-1 (ACP1) and led to the assignment of the AN1 locus on chromosome 2p, has been updated and expanded. Linkage analysis between the aniridia phenotype and ACP1 does not support the original linkage results, excluding linkage up to theta = 0.17 with Z = -2. Tests for linkage to other chromosome 2p markers. APOB, D2S71, D2S5, and D2S1, also excluded linkage to aniridia. Markers that have been isolated from the chromosome 11p13 region were then analyzed in this aniridia family. Two RFLPs at the D11S323 locus give significant evidence for linkage. The PvuII polymorphism detected by probe p5S1.6 detects no recombinants, with a maximum lod score of Z = 6.97 at theta = 0.00. The HaeIII polymorphism detected by the probe p5BE1.2 gives a maximum lod score of Z = 2.57 at theta = 0.00. Locus D11S325 gives a lod score of Z = 1.53 at theta = 0.00. These data suggest that a locus for aniridia (AN1) on chromosome 2p has been misassigned and that this autosomal dominant aniridia family is segregating for an aniridia mutation linked to markers in the 11p13 region. PMID- 1505983 TI - Assignment of the human glycogen debrancher gene to chromosome 1p21. AB - Glycogen debranching enzyme is a monomeric protein containing two independent catalytic activities of glycantransferase and glucosidase that are both required for glycogen degradation. Its deficiency causes type III glycogen storage disease. A majority of the patients with this disease have deficient enzyme activity in both liver and muscle (type IIIa) but approximately 15% of them lack enzyme activity only in the liver (type IIIb); however, the enzyme is a monomer and appears to be identical in all the tissues. The cDNA coding for the complete human muscle debranching enzyme has recently been isolated. Using the cDNA clones, the debrancher gene was localized to human chromosome 1 by somatic cell hybrid analysis. Regional assignment to chromosome band 1p21 was determined by in situ hybridization. Mapping of the debrancher gene to a single chromosome site is consistent with our hypotheses that a single gene encodes both liver and muscle debrancher protein. PMID- 1505984 TI - Automatable screening of yeast artificial-chromosome libraries based on the oligonucleotide-ligation assay. AB - The systematic screening of yeast artificial-chromosome (YAC) libraries is the limiting step in many physical mapping projects. To improve the screening throughput for a human YAC library, we designed an automatable strategy to identify YAC clones containing a specific segment of DNA. Our approach combines amplification of the target sequence from pooled YAC DNA by the polymerase chain reaction (PCR) with detection of the sequence by an ELISA-based oligonucleotide ligation assay (OLA). The PCR-OLA approach eliminates the use of radioactive isotopes and gel electrophoresis, two of the major obstacles to automated YAC screening. Furthermore, the use of the OLA to test for the presence of sequences internal to PCR primers provides an additional level of sensitivity and specificity in comparison to methods that rely solely on the PCR. PMID- 1505985 TI - Determination of the exon structure of the distal portion of the dystrophin gene by vectorette PCR. AB - The structure of the 3' one-third of the dystrophin gene has not previously been established. We have used vectorette PCR on a yeast artificial chromosome containing part of the human dystrophin gene to determine that there are 20 exons in this region and to characterize adjacent intron sequences of each one. Combined with previous information on the remainder of the gene, this study shows that the coding sequence is distributed between 79 exons. We have used PCR between exons to measure the distances that separate the more closely clustered exons. Vectorette PCR products were used as probes on Southern blots to assign all the 3' exons to genomic HindIII fragments that are commonly detected in the analysis of dystrophin gene deletions. The results will be useful for determining the effect of genomic deletions on the translational reading frame, for setting up genomic PCR assays to confirm point mutations, for analyzing splice site mutations, and for investigating potential cis-acting elements involved in tissue specific alternative splicing. Vectorette PCR using primers derived from cDNA sequence represents an efficient and widely applicable method for establishing gene structure and obtaining intron sequence flanking exons, starting from a genomic clone and a cDNA sequence. PMID- 1505986 TI - On the relative importance of marker heterozygosity and intermarker distance in gene mapping. AB - Molecular biologists are often confronted with the problem of whether they should try to generate large numbers of very closely linked markers of low heterozygosity or smaller numbers of less closely linked markers of high heterozygosity. In other words, What is more important for gene mapping, high marker heterozygosity or dense marker spacing? We investigated that problem by analytically computing the expected lod score per meiosis in which the new locus is informative and phase known. We also looked at the length of the 1-unit-of-lod score support interval for the expected lod score from 100 such meioses. We found that while both quantities have an influence on the number of meioses needed to find linkage, the length of the support interval is almost entirely dependent on the intermarker distance, for heterozygosities between 20 and 100%. However, the probability of any given meiosis being phase known and the ability to develop an accurate map of the markers are functions of marker heterozygosity, further complicating the issue. PMID- 1505987 TI - Identification of new markers in Xp21 between DXS28 (C7) and DMD. AB - Characterization of Xp21 distal to Duchenne muscular dystrophy (DMD) in the region containing the genes for adrenal hypoplasia congenita (AHC) and glycerol kinase deficiency (GKD) has been limited due to a paucity of probes. Two probes were localized between DXS28 (C7) and AHC, the yeast artificial chromosome insert YHX39 (DXS727) and the polymorphic phage clone QST59 (DXS319). A genomic clone, FT1 (DXS726), 3' to DMD, was also characterized. Portions of the three probes were sequenced and primer pairs were generated to amplify a sequence-tagged site within each probe. Amplification of DNA from patients confirmed the deletion results obtained by Southern blot analysis, and these three sequence-tagged sites were successfully combined for triplex PCR. In addition to facilitating molecular genetic diagnosis in Xp21, these probes can be used to identify additional YACs and other probes to further increase the genomic information and diagnostic capabilities in this region. PMID- 1505988 TI - Chromosomal localization of seven neuronal nicotinic acetylcholine receptor subunit genes in humans. AB - We have determined the chromosomal location of seven human neuronal nicotinic acetylcholine receptor subunit genes by genomic Southern analysis of hamster/human somatic cell hybrid DNAs. The beta 2 subunit gene was localized to human chromosome 1, the alpha 2 and beta 3 subunit genes were localized to human chromosome 8, the alpha 3, alpha 5, and beta 4 subunit genes were localized to human chromosome 15, and the alpha 4 subunit gene was localized to human chromosome 20. Mapping of the beta 2 subunit gene to chromosome 1 establishes a syntenic group with the amylase gene locus on human chromosome 1 and mouse chromosome 3, while mapping of the alpha 3 subunit gene to chromosome 15 confirms the existence of a syntenic group with the mannose phosphate isomerase gene locus on human chromosome 15 and mouse chromosome 9. PMID- 1505989 TI - Dissecting (CAC)5/(GTG)5 multilocus fingerprints from man into individual locus specific, hypervariable components. AB - Individual components of multilocus fingerprints from man produced by (CAC)5/(GTG)5 oligonucleotides have been scrutinized to characterize their peculiar properties. Successful cloning and changes occurring during the propagation of recombinant simple repetitive DNA in prokaryotic hosts are described. The isolated locus-specific probes were characterized with respect to their formal (and population genetic) properties and their usefulness for individualization and linkage studies. The localization was determined on chromosomes 8, 9, 11, and 22. Repeat flanking sequences were characterized and analyzed for their coding potential because of significant open reading frames and apparent evolutionary conservation among vertebrates. The organization of the repeats and their flanking regions in the human genome is discussed with respect to the sequence (fine) architecture that developed during evolution. Classical "minisatellite" sequences were not detected near hypervariable (cac)n/(gtg)n repeats. The single-copy probes described herein are a convenient complement to the oligonucleotides employed for multilocus fingerprinting. Many practical applications are apparent. PMID- 1505990 TI - Fine-mapping of the spinal muscular atrophy locus to a region flanked by MAP1B and D5S6. AB - The microtubule-associated protein 1B (MAP1B) locus has been mapped in close proximity to spinal muscular atrophy (SMA) on chromosome 5q13. We have identified a second microsatellite within a MAP1B intron, which increases the heterozygosity of this locus to 94%. Two unambiguous recombination events establish MAP1B as a closely linked, distal flanking marker for the disease locus, while a third recombinant establishes D5S6 as the proximal flanking marker. The combination of key recombinants and linkage analysis place the SMA gene in an approximately 2-cM interval between loci D5S6 and MAP1B. Physical mapping and cloning locate MAP1B within 250 kb of locus D5S112. The identification and characterization of a highly polymorphic gene locus tightly linked to SMA will facilitate isolation of the disease gene, evaluation of heterogeneity, and development of a prenatal test for SMA. PMID- 1505991 TI - Clustering of C2-H2 zinc finger motif sequences within telomeric and fragile site regions of human chromosomes. AB - Ninety-three phage clones identified by hybridization with a C2-H2 zinc finger sequence probe have been grouped into 23 genetic loci. Partial sequencing verified that each locus belonged to the zinc finger family. Oligonucleotide primer pairs were developed from these sequences to serve as STS markers for these loci. One or more clones from each locus was mapped onto human metaphase chromosomes by fluorescence in situ hybridization. Several loci map to identical chromosomal regions, indicating the possible presence of multigene clusters. Zinc finger loci were found to reside predominantly either in telomeric regions or in chromosomal bands known to exhibit chromosome fragility. Chromosome 19 carries a disproportionate fraction (10 of 23) of the mapped zinc finger loci. PMID- 1505992 TI - Multiple-model adaptive predictive control of mean arterial pressure and cardiac output. AB - A multiple-model adaptive predictive controller has been designed to simultaneously regulate mean arterial pressure and cardiac output in congestive heart failure subjects by adjusting the infusion rates of nitroprusside and dopamine. The algorithm is based on the multiple-model adaptive controller and utilizes model predictive controllers to provide reliable control in each model subspace. A total of 36 linear small-signal models were needed to span the entire space of anticipated responses. To reduce computation time, only the six models with the highest probabilities were used in the control calculations. The controller was evaluated on laboratory animals that were either surgically or pharmacologically altered to exhibit symptoms of congestive heart failure. During trials, the controller performance was robust with respect to excessive switching between models and nonconvergence to a single dominant model. A comparison is also made with a previous multiple-drug controller design. PMID- 1505993 TI - A random dipole model for spontaneous brain activity. AB - The statistical properties of the EEG and the MEG are described mathematically as the result of randomly distributed dipoles. These dipoles represent the interactions of cortical neurons. For certain dipole distributions, the first- and second-order moments of the electric and magnetic fields are derived analytically. If the dipoles are in a spherical volume conductor and have no preference for any direction, the variance of a differentially measured EEG signal is only a function of the electrode distance. In this paper, the theoretically derived variance function will be compared with EEG- and MEG measurements. It is shown that a dipole with a fixed position and a randomly fluctuating amplitude is an adequate model for the alpha-rhythm. An expression for the covariance between the magnetic field and a differentially measured EEG signal is derived. This covariance is considered as a function of the magnetometer position, and is compared with the measurements of Chapman et al. [23]. The theory can be used to obtain a (spatial) covariance matrix of the background noise, which occurs in evoked potential measurements. Such a covariance matrix can be used to obtain a maximum likelihood estimator of the dipole parameters in evoked potential studies, to evaluate the merits of the so called "Laplacian derivation," and for the interpolation of electromagnetic data. PMID- 1505994 TI - Equivalent source estimation based on the calculation of the electric field from depth EEG data. AB - This paper describes a method for the estimation of equivalent source position and strength based on the estimation of the electric field from depth electroencephalographic (EEG) data. The calculation method for the electric field is based on a tetrahedral geometry. The proposed approach for source parametrization is twofold. Firstly, the distribution of electrical energy by the squared norm of the electric field vector can give an estimate of the source position, without having to assume a dipole source. Secondly, the average electric field can be related to the dipole magnitude and orientation of the equivalent source. Simulation results demonstrate the potential usefulness of the method. The effects of noise and sampling, and the geometry of the measurement system (i.e., implanted electrodes) relative to the source are also investigated through simulations. PMID- 1505995 TI - Detection of reentry currents in atrial flutter by magnetocardiography. AB - We discuss the use of magnetocardiography to detect reentry currents in cardiac flutter and fibrillation. The magnetic field produced by induced atrial flutter was measured in isolated rabbit hearts. A moving dipole model is proposed to treat the experimental data and to locate the reentry path. PMID- 1505996 TI - Direct computation of ultrasound phased-array driving signals from a specified temperature distribution for hyperthermia. AB - This paper presents a new method which obtains ultrasound hyperthermia applicator phased-array element driving signals from a desired temperature distribution. The approach combines a technique which computes array element driving signals from focal point locations and intensities with a new technique which calculates focal point locations and power deposition values from temperature requirements. Temperature specifications appear here as upper and lower bounds within the tumor volume, and a focal point placement algorithm chooses focal patterns capable of achieving the temperature range objective. The linear algebraic structure of the method allows rapid calculation of both the phased-array driving signals and an approximate temperature field response. Computer simulations verify the method with a spherical section array (SSA) for a variety of temperature specifications and blood perfusion values. This scheme, which applies to any phased-array geometry, completes an essential step in both treatment planning and feedback for hyperthermia with ultrasound phased-array applicators. PMID- 1505997 TI - Direct use of CT scans for hyperthermia treatment planning. AB - In the field of deep regional hyperthermia cancer therapy, the BSD-2000 Hyperthermia System is one of the most widely used devices. Because of the complexity of the treatment process, computer modeling has long been viewed as a desirable means of planning patient treatments. Patient-specific, three dimensional computer modeling for treatment planning in the BSD-2000 has been in clinical use at this institution for two years. Two of the persistent problems have been the large amount of time needed to create the patient model from a computed tomography (CT) scan (one and a half days), and the lack of a way to view the large amounts of data that comprise the output of a treatment plan, i.e., the specific absorption rate (SAR) at 20,000 to 30,000 cells. Here we present a method that obtains the dielectric properties needed for hyperthermia treatment planning directly from the CT image with minimum operator interaction, a process which takes about a half day and is more accurate. Comparison is made with the previous method of drawing contours around the different tissue types. We further describe a method which displays the output as iso-SAR contours directly over the CT scan of the patient. PMID- 1505998 TI - Distinguishability in impedance imaging. AB - Impedance imaging systems apply currents to the surface of a body, measure the induced voltages on the surface, and from this information, reconstruct an approximation to the electrical conductivity in the interior. This paper gives a detailed discussion of several ways to measure the ability of such a system to distinguish between two different conductivity distributions. The subtle differences between these related measures are discussed, and examples are provided to show that these different measures can give rise to different answers to various practical questions about system design. PMID- 1505999 TI - Comparison of algorithms for tracking short-term changes in arterial circulation parameters. AB - Three recursive methods especially suited for identification of systems with rapidly changing parameters are applied to tracking of the viscoelastic properties of the systemic arterial bed. These methods include two least squares (LS) algorithms with constant or variable forgetting factor (RLS and LSVF) and a LS algorithm incorporating both a constant forgetting factor and covariance modification (CFCM). The methods are presented in a unified framework and their sensitivity with respect to the design variables is investigated using noisy data from computer simulations. All analysed methods have shown themselves to be able to satisfactory track rapid changes in peripheral resistance. The LSVF method, which offers slightly better performances than the classical RLS, may be preferred when calculation efficiency is the prime requirement. The CFCM algorithm, although maintaining reasonable simplicity, shows the best tracking ability also on varying of the noise sequence. PMID- 1506000 TI - On detecting the presence of fetal R-wave using the moving averaged magnitude difference algorithm. AB - An efficient algorithm detecting the presence of a fetal QRS complex is presented. The proposed fetal QRS detection method computes the averaged magnitude of the difference between the fetal ECG signal and the reference signal to detect the fetal QRS event. The detected fetal QRS complexes are exponentially averaged to generate the template signal which can track the slowly varying shape of the fetal ECG signal. As an effort to obtain improved detection performances, two approaches of normalizing the fetal ECG signal and the template are considered. PMID- 1506001 TI - Muscle input-output model: the static dependence of force on length, recruitment, and firing period. AB - Steady-state isometric active muscle force has a bilinear dependence on length and firing period (inverse of firing rate). At a fixed length, force increases linearly with decreasing firing period. The slope decreases linearly with increasing muscle length, and the value of force extrapolated to zero firing period remains constant. This relationship can be used in Hill-type muscle models. PMID- 1506002 TI - Comments on "Some imaging parameters of the oblique dipole layer cardiac generator derivable from body surface electrical potentials". PMID- 1506003 TI - Role of interleukin-1 in infectious diseases. PMID- 1506004 TI - Cytokines and growth factors in the pathogenesis of AIDS-associated Kaposi's sarcoma. AB - In the past, the study of KS pathogenesis has been hampered by the lack of in vitro and in vivo experimental systems. Recently, the establishment of long-term cultures of KS spindle cells and the development of animal models have allowed a variety of studies on the pathobiology of the disease. The results from these studies, reviewed herein, indicate that KS is a cytokine-mediated disease and that inflammatory and angiogenic cytokines and the HIV-1 Tat protein cooperate in its induction and progression in HIV-1-infected individuals. PMID- 1506005 TI - Different role of cytokine mediators in septic shock related to meningococcal disease and surgery/polytrauma. AB - So far, there has been a tendency towards a uniform concept of the role and kinetics of TNF and other cytokines in septic shock. However, our comparison of data from different groups of shock patients clearly demonstrates marked differences. On the one hand, the cytokine pattern in experimental septic shock and meningococcal disease has similarities which include early burst releases of TNF and IL-6. On the other hand, intensive care unit patients which includes patients with polytrauma, surgery, burns and other underlying diseases have a completely different pattern of appearance of TNF and IL-6 in the circulation. We have not been able to detect bioactive TNF in the circulation of these patients, whereas others have measured elevated levels of immunoreactive TNF. Bioactive IL 6 can be detected in serum; however, the levels are often fluctuating and there is no common pattern of appearance. These differences probably reflect differences in the release of endotoxin and the immunological status of the patients. TNF inhibitors and soluble TNF receptors probably play an important role. Experimental models for septic shock most commonly use administration of live bacteria or endotoxin to anesthesized healthy animals. This appears to be a good model for meningococcal disease, but not for intensive care unit patients. PMID- 1506006 TI - Cytokines in infectious diseases. PMID- 1506007 TI - Non-parasite-specific cytokine responses may influence disease outcome following infection. PMID- 1506008 TI - Bacterial toxin-induced cytokine production studied at the single-cell level. PMID- 1506009 TI - Cytokines, Toxoplasma and intracellular parasitism. PMID- 1506010 TI - Pathogenesis of wasting disease after cyclophosphamide treatment of neonatal mice. AB - Cyclophosphamide is a potent immunosuppressive agent and is being widely used in organ transplantation. The effects of this anti-rejection drug on lymphoid organs are poorly understood. Newborn Swiss mice injected with various doses of cyclophosphamide suffered from wasting disease at 4 weeks post treatment. The incidence of wasting disease was dose dependent. Haematological picture of the wasting animals revealed leukocytosis of variable degree. Lymphocyte/granulocyte ratio was not inhibited. The cyclophosphamide treatment caused shrinkage of lymphoid organs. Bone marrow showed degeneration of haematopoietic cells. The failure to sustain lymphopoiesis by the potential lymphoid sites following cyclophosphamide treatment and the associated immunological insufficiency resulted in the fatal wasting disease. PMID- 1506011 TI - Effect of directional selection on spontaneous male recombination in Drosophila ananassae. AB - Artificial selection was carried out for high and low spontaneous male recombination values in D. ananassae for nine generations by using cu b se marker (second chromosome) and wild stocks which were free from heterozygous chromosome inversions. The mean crossing-over frequency of nine generations was 2.22, 0.70 and 1.20% in high, low and control lines respectively. The values of regression coefficient and realized heritability also indicated that male recombination was affected by selection. However, response to selection was more pronounced in high line as compared to low line. This provides evidence that spontaneous male crossing-over in D. ananassae is under polygenic control. PMID- 1506012 TI - Purification of Salmonella stanley enterotoxin and its immunology and dermatotoxicity. AB - Isolation of an enterotoxic factor from cell-free-culture-supernatant of S. stanley was achieved to homogeneity using salt precipitation, dialysis and molecular seive chromatography through Sephadex G-100 and G-200 columns. The purified enterotoxic factor yielded a single protein band on polyacrylamide gel electrophoresis, induced antibodies in the rabbit and showed single band on agar gel precipitation. It induced fluid accumulation in the rabbit ligated ileal loop (RLIL) and was neutralized by the homologous antiserum. Antigenically it was not related to cholera toxin but with enterotoxin of other Salmonella serotypes. It also exerted dermatotoxic effect in the rabbit skin causing marked central necrosis with peripheral erythema. PMID- 1506013 TI - Anxiogenic activity of quinine--an experimental study in rodents. AB - Quinine, a cinchona alkaloid, was investigated for putative anxiogenic activity in view of clinical reports suggesting that it induces anxiety and apprehension following its use in malaria. The experimental paradigms chosen to elucidate anxiogenic activity have been shown to stand the tests of reliability and validity. Yohimbine, which has been shown to induce anxiety both in animals and in man, was used for comparison. Quinine was found to elicit a complex behavioural profile of activity ranging from overt central stimulation to marked central depression on dose increment. The doses 10 and 20 mg/kg, ip, of quinine chosen to investigate anxiogenic activity were comparable to those induced by 2.5 and 5 mg/kg ip of yohimbine. Quinine induced a dose-related anxiogenic activity in the open-field and elevated plus-maze tests in mice, and the social interaction and thirst conflict tests in rats, similar to effects induced by yohimbine. In addition, both quinine and yohimbine attenuated the effects of diazepam, an anxiolytic agent, in the open-field and thirst conflict tests. The results indicate that quinine exerts significant anxiogenic effect at a particular dose range. PMID- 1506014 TI - Antiinflammatory and antipyretic activity of vicolides of Vicoa indica DC. AB - Vicolides A,B, C and D, the sesquiterpene lactones isolated from V. indica exhibited antiinflammatory activity against cotton pellet granuloma in rats at dose level of 10 mg/kg body weight, sc. Highly significant activity was observed with vicolides C and D. They reduced the protein content, acid and alkaline phosphatase, glutamate-pyruvate transaminase and glutamate oxaloacetate transaminase activities in liver and serum. Significant reduction in ascorbic acid content in adrenals was also observed in treated animals. The highly significant antiinflammatory activity of vicolides C and D can be attributed to their chemical structures. Vicolide D has an epoxy angeloyl group while vicolide C has 3,4 epoxy group and an ester moiety in the molecule. Vicolide D possesses antipyretic activity at 250 mg/kg body weight, po dose. It may be due to the presence of epoxy angeloyl group in the molecule. PMID- 1506015 TI - Distribution pattern and dose-response-relationship of chromosome aberrations in human lymphocytes induced in vitro by 60Co gamma-rays and 110 kV X-rays. AB - Peripheral blood lymphocyte culture system was used to construct reference dose response curves for 60Co gamma-rays and 110 kV X-ray-induced chromosome aberrations at 6 dose points ranging from 0.25 to 4.0 Gy. Qualitative and quantitative differences between these two types of radiation for the yield of induced aberrations and their distribution pattern were analysed. Experimental data of aberration yields were compared after fitting them to five different dose response models. The yields of chromosome aberrations in particular dicentrics, gave a good fit to linear-quadratic besides linear and power models. In this model, single-track events predominated over double-track events for both the qualities of radiation used. The pattern of distribution was mainly Poisson for dicentrics but gave a conflicting result for acentrics which was in excess. PMID- 1506016 TI - Termination of photorefractoriness in the brahminy myna, Sturnus pagodarum: role of photoperiods and gonadal hormones. AB - In brahminy myna a photosensitive species, long days caused full gonadal development followed by rapid regression, whereas short days inhibited these responses. Experiments were performed to investigate the effects of duration of photoperiod and gonadal hormones on the recovery of photosensitivity to long photoperiods in male birds. Groups of photorefractory birds were subjected to 8-, 9- or 11-hr daily photoperiods for 45 (6.5 weeks) or 63 (9 weeks) days and then transferred to 15 h daily photoperiods for 60 days to check for the regaining of photoresponsivity. A control group was held under 15L:9D throughout the period of study. Another experiment included three groups of photorefractory males, which were maintained on 9L:15D for 9 weeks and administered with, birth-1day-1 alternately for first 30 days olive oil or different doses (10 or 100 micrograms) of testosterone propionate (TP)/bird/day alternately for first 30 days, and then transferred to 15L:9D for another 30 days to test the recovery of photosensitivity. The results indicated that (i) a period of exposure to short daylengths is required to dissipate photorefractoriness, (ii) termination of photorefractoriness is dependent on the length and duration of photoperiods and (iii) TP inhibits the recovery of photosensitivity in a dose dependent manner. PMID- 1506017 TI - Chemotactic detection of incipient ovarian follicular atresia. AB - Chemotactic activity was measured in the follicular fluid collected from normal and atretic Graafian follicles isolated from the rat ovaries. The atresia of Graafian follicles was induced by pentobarbitone injections for 3 days beginning the day of proestrous. The chemotactic activity, as measured by direct morphological evaluation of cellular locomotion of individual cells and Boyden leading front assay, was significantly higher in follicular fluid from atretic follicles and it showed a progressive increase from day 1 to day 3 of blockade of ovulation. In vitro exposure of blocked follicles to PMSG and hCG on day 1, 2 and 3 failed to alter the chemotactic response of leukocytes towards follicular fluid of atretic follicles. Increased chemotaxis in the follicular fluid after 24 hr of blockade of ovulation appears to form an important criterion to identify atretic follicles well in advance, before the morphological symptoms of degeneration become apparent and the incipient change once induced in follicles is not reversed by gonadotropins. PMID- 1506018 TI - Reversal of T-cell unresponsiveness through serine-esterase inhibitors mediated enhanced lymphokine induced microbicidal activities in kala-azar. AB - After presenting processed glycoprotein of Leishmania donovani to T-cell, macrophage seeks the help of a panel of T-cells lymphokines to transform from a state that sustains intra cellular replication of parasite to an effector state for destructing parasites. But esterase and trypsin of macrophage membrane prevent T-cells to release MIF. Role of soya-bean trypsin inhibitor (STI) has been exposed in the present study with a view to alter esterase functional behaviour of macrophage for control of T-cell activation and also, if T-cells once made responsive to antigen by STI do alter macrophage response to T-cells or not. Results establish STI as potent effector molecule, which can serve as an adjuvant to candidate T-cell epitope and synthetic peptide for development of anti-Kala-azar vaccine protocol in future. PMID- 1506019 TI - Effect of radiation on some haematological parameters and its modification by vitamin E in chicks. AB - White leghorn male chicks of 1 and 7 day age groups were studied for acute (2.25 Gy) gamma radiation (with or without vit. E pretreatment) induced haematological changes in the peripheral blood at days 1, 3, 5, 7, 14 and 28 postirradiation. A continuous decrease in the erythrocyte numbers was observed in the animals irradiated without vit. E treatment. The changes in haematocrit, haemoglobin, MCV, MCH and MCHC values were in line with the erythrocytic changes reflecting radiation induced damage to the erythroid elements. Animals pretreated with vit. E show lesser depression in the erythrocytic component at all the stages indicating its radio-protective influence. The significant increase in the immature RBC's in the peripheral blood in vit. E treated animals after irradiation, implies enhanced erythropoiesis. PMID- 1506020 TI - In vivo sister chromatid differentiation and baseline sister chromatid exchanges in a mouse ascites tumour model. AB - Induction of differentially stained sister chromatids at G2/M and determination of baseline sister chromatid exchanges (SCEs) in ascites form of mouse sarcoma 180 cell line have been done by in vivo incorporation of 5-bromodeoxyuridine (BrdU) for two consecutive DNA replication cycles. The baseline SCE frequency is 6.24 at log phase of tumour growth. PMID- 1506021 TI - Effects of organophosphorus insecticide phosphomidon on antioxidant defence components of human erythrocyte and plasma. AB - Effect of organophosphorus insecticide, phosphomidon (250 and 500 ppm) on human erythrocyte and plasma were studied in vitro to get insight into the cellular antioxidant defence mechanism and malondialdehyde formation. The antioxidant defence system of erythrocyte was altered as evident by depression of glutathione reductase, glucose 6 phosphate dehydrogenase, whereas the level of reduced glutathione, glutathione peroxidase, glutathione-S-transferase, superoxidedismutase and catalase were stimulated. In the case of plasma fraction, glutathione reductase, glutathione peroxidase, glutathione-s-transferase, glucose 6-phosphate dehydrogenase, superoxide dismutase and levels of reduced glutathione were significantly depressed and the malondialdehyde formation and catalase activity were elevated indicating the less adaptive response of plasma to protect it from oxidative damage. PMID- 1506022 TI - Effect of picroliv on protein and nucleic acid synthesis. AB - Oral administration of picroliv, a standardised fraction of roots and rhizomes of Picrorhiza kurroa, showed stimulation of nucleic acid and protein synthesis in rat liver. Results are comparable with a standard hepatoprotective agent, silymarin. PMID- 1506023 TI - Dosage compensation for a chromosome that comprises an X chromosome and an autosome as its two homologs in interspecific hybrids of Drosophila miranda and D. persimilis. AB - A chromosomal element (C) of an interspecific hybrid of D. miranda (females) and D. persimilis (males) represented a unique situation, where between its two homologous, one derived from an X chromosome (X2 of miranda) and the other from an autosome (3rd chromosome of persimilis). In cytological preparations of polytene nuclei, the X chromosomal homolog in hybrid males exhibited the male-X like inflated structure, known as prerequisite for hypertranscription; whereas the autosomal homolog existed as an haploid autosomal arm. In hybrid females, both the homologs had similar diameter and stainability. This difference in cytomorphology of the X2 homolog between two sexes made the C element potential to transcribe higher in males than in females, raising the inevitable question of compensation. Cellular autoradiography, using 3H-UR, was employed to measure the total transcription of the C element (X2 + 3rd) in hybrid sexes. Results revealed that, although the X2-homolog was hyperactive in males, the total transcription of the C element was equal (relative to autosomal transcription) in both hybrid sexes, and this was achieved in expense of the transcription of the 3rd chromosomal homolog in males. Thus, apart from X-chromosomal and autosomal dosage compensation, the existence of an X-autosomal dosage compensation in Drosophila is evident in the present work. PMID- 1506024 TI - Demonstration of two forms of vitellogenin in serum of estradiol-17 beta-treated Indian major carp, Labeo rohita. AB - Vitellogenin (Vg) synthesis was induced in the male and non-vitellogenic female Rohu, the Indian major carp, by estradiol-17 beta(E2) where effect was more in female. A crude preparation of Vg was isolated in the second peak after gel filtration on Ultrogel AcA 34 from the sera of vitellogenic female Rohu and E2 treated male and female Rohu. Estimation of alkali-labile phosphorus was shown to be used as an index of Vg. Native-PAGE analysis has revealed the presence of two forms of Vg (Vg1: 430,000 dalton and Vg2:240,000 dalton) in Vg fraction obtained after gel filtration as well as in the sera of E2-treated male and female Rohu. Immunological cross-reaction studies between antiserum to yolk protein and Vg fractions as well as the sera from E2-treated male and female Rohu further indicates the presence of two precipitin lines (not clearly visible as the two lines fused to form a thick line) suggesting the occurrence of two forms of Vg in the Rohu. PMID- 1506025 TI - 'Dark' cell formation under protein malnutrition: process of conversion and concept of 'semi-dark' type Purkinje cells. AB - This paper deals with some deleterious effects of protein malnourishment in rat cerebellum. Severe protein deprivation enhanced the formation of 'dark' cells in white rats. It is postulated that abnormal changes in the neuronal contents induced by nutritional stress play a vital role in the formation of the 'dark' cells through an intermediary stage, 'semi-dark' cells. Centrophenoxine a lipofuscinolytic agent, however, seems to interfere with the process of formation of 'dark' cells and/or helps reconversion of the 'dark' cells into the normal or 'light' type Purkinje cells. PMID- 1506026 TI - Microscopic anatomy of small intestine of Macaca radiata with special reference to gut associated lymphoid tissue. AB - The hitherto unreported microscopic anatomy of the small intestine of the bonnet monkey (M. radiata) was studied. There was a striking similarity in the general structure and cellular composition of the small intestine of the animal and that of humans. Of special interest was our observation of the occurrence of cells interspersed in the follicle associated epithelium which were morphologically similar to human M cells. These cells were pale, devoid of a brush border and frequently had lymphocytes apparently enclosed within them. PMID- 1506027 TI - Differential radioprotection of tissues in C3H/J mice by a combination of 5 hydroxy L-tryptophan with 2-aminoethylisothiuronium bromide hydrobromide. AB - Differential radioprotection between normal tissues and carcinoma was observed in C3H/J mice treated with a combination of 5-hydroxy L-tryptophan (5-HTP, 100 mg/kg) and 2-aminoethylisothiuronium bromide hydrobromide (AET, 20 mg/kg). Protection to normal tissues was judged by LD50(30) and by radiation induced damage to bone marrow(BM) using clonogenic ability of blood forming stem cells (10 day CFUs) as the criteria. Pretreatment with 5-HTP + AET combination 30 min before whole body gamma radiation (WBGR) enhanced the recoveries of the number of blood forming stem cells in BM of irradiated mice after 0, 7th and 10th day of irradiation. LD50(30) for C3H/J mice was 7.3 Gy and the dose modifying factor (DMF) of 5-HTP + AET combination was 1.76. On the contrary, pretreatment with this combination did not protect the mammary carcinoma transplanted in C3H/J mice, when exposed to 80 Gy soft X-rays. PMID- 1506028 TI - Induction and regulation of alpha-amylase synthesis in a cellulolytic thermophilic fungus Myceliophthora thermophila D14 (ATCC 48104). AB - The alpha-amylase enzyme synthesis was higher when M. thermophila D-14 (ATCC 48104) was grown in culture medium incorporated with starch or other carbohydrates containing maltose units. Maximum enzyme production was attained with 1% starch followed by a gradual decrease with increasing concentration. Marked decrease in alpha-amylase synthesis occurred with the addition of glucose to the culture medium and this decreasing activity was proportional to the concentration of glucose. The enzyme synthesis was resumed as soon as the glucose concentration fell below a critical level. The addition of cAMP did not eliminate the repressive activity of glucose. The findings suggest that extracellular alpha amylase synthesis in M. thermophila D-14 was inducible and subject to catabolite repression. PMID- 1506029 TI - A rapid method for flow cytometric cell counting and cell cycle analysis from monolayer cultures of tumor cells. AB - A rapid, simple, and reliable flow cytometric method using the histochemical fluorescent stain Hoechst 33342 in presence of the non-ionic detergent Triton X 100 has been reported. The processing of melanoma cell cultures to get nuclei stained with the fluorescent dye was accomplished in one step and within an hour permitted concurrent flow cytometric measurement of cell density and cell cycle analysis. The preparation is stable for more than three weeks at room temperature for flow cytometry. The histograms are reproducible and exhibit a coefficient of variation of less than 2.5% (G1 peak). The cell density measurements varied within +/- 5% limits. PMID- 1506030 TI - Effect of metal mixtures on activity of two respiratory enzymes and their recovery in Oreochromis mossambicus (Peters). AB - Effects of sublethal doses of metal (Cu, Cd, Zn) mixtures on the activities of key respiratory enzymes (succinate dehydrogenase, SDH and glyceraldehyde dehydrogenase, GDH) and their recovery following withdrawal of treatments were studied in the freshwater fish O. mossambicus. On the basis of 96 hr LC50 Cu was highly toxic followed by Zn and Cd, and the trimetal combination (Cu+Zn+Cd) was extremely toxic than any other combination; combination of Zn+Cd was least toxic. A significant gradual decrease in SDH with a concomitant increase in GDH activity observed in liver, brain, muscle and gill of animals exposed to metal suggest a metabolic shift from aerobiosis to anaerobiosis due to metal action. Exposed individuals when transferred to metal impoverished water showed an improvement in SDH activity and decline in GDH activity suggesting slow reversal to aerobic metabolism. O. mossambicus needs more time for complete recovery. PMID- 1506031 TI - Studies on cell growth and development of Dictyostelium discoideum treated with carbaryl, a pesticide. PMID- 1506033 TI - Evaluation of drug effects on spinal cord injury--an experimental study in monkeys. AB - Contusion injury is produced experimentally in anaesthetised monkeys by weight drop method. A group of animals having laminectomy alone served as sham controls. Drugs were administered 30 min after injury initially. Naloxone and nifedipine were administered as single dose administration immediately after injury. Dipyridamole and DMSO were administered daily for a period of 1 week. Acetylcholinesterase (AchE) was estimated in 2 spinal tissue segments, S1-at the site of injury and S2-the segment above the site of injury, at the end of 1 week after sacrificing the animals. Contusion injury produced significant decrease in specific activity of AchE in the traumatised segment of the experimental animals. The non-traumatised adjacent segment did not show any significant change. Nifedipine, naloxone and DMSO produced a decrease in AchE activity in S1 and S2 segments. Monkeys developed paraplegia after contusion injury. A score 2+ was observed after 1 week as compared to the score of 4+ of sham controls. Single dose administration of naloxone seemed to reverse the motor deficit by getting a score of 3+; other drugs did not produce any beneficial effect on motor deficit. PMID- 1506032 TI - Inhalation toxicity of methylisocyanate: assessment of germ cell mutagenicity and reproductive effects in rats. AB - Adult male Wistar rats were exposed to methylisocyanate (MIC, 3.2 mg/l, single inhalation exposure for 8 min under static condition) or ethyl methanesulphonate (EMS, 150 mg/kg, single ip dose) for the assessment of germ cell mutagenicity and reproductive effects. Sequential matings of treated males with normal females on days 1-7, 8-14 and 15-21 post-exposure did not indicate any induction of dominant lethal mutation (increased frequency of preimplantation losses and early fetal deaths) by MIC but it was significantly induced by EMS as compared to respective controls. Males, necropsied after 21 days of exposure, showed no effect of MIC on epididymal sperm density and morphology. EMS also had no effect on sperm density but it significantly induced morphological abnormalities in sperm as compared to untreated controls. There was an acute and transitional reduction in reproductive performance (10-21%) of MIC-exposed males during days 1-14 post-exposure followed by recovery to the normal level during days 15-21 post-exposure. The progeny of MIC-exposed males was also normal in terms of litter size, litter weight, neonatal survival and body weight gain in litters up to 10 days post-partem. It is concluded with the evidence at hand that the observed failure of MIC to cause germ cell mutagenicity is related to its poor biodistribution to the target site(s) and a transient reduction in the reproductive performance of MIC-exposed males is a result of general stress and disconsolate copulation. PMID- 1506034 TI - Bioactivity of marine organisms: Part VI--Screening of some marine flora from Indian coasts. AB - Alcoholic extracts of 50 botanically identified species of marine flora have been screened for a wide range of biological activities. Of these, 2 extracts exhibited anti-amoebic and antiviral activity each, 3 of them had anti implantation activity; 9 had hypoglycaemic activity while hypotensive activity was associated with 11 extracts; 14 extracts were found to be diuretic and 1 of them had anti-inflammatory activity. Further, 10 of these extracts exhibited 2 types of activities while a combination of 3 and 4 types of activities was observed in one extract each. Follow-up studies have been carried out in some plants with confirmed activity. The active principles and results of these studies are reported. PMID- 1506035 TI - Metabolism of very low density lipoproteins--effect of sardine oil. AB - The effect of feeding fish oil on the metabolism of lipoproteins was studied in rats. Rats were fed diet containing 10% sardine or groundnut oil for 6 weeks. There was a significant decrease in the total cholesterol, phospholipids and triglycerides as well as the amount of the lipids associated with VLDL and LDL in serum in fish oil-fed rats. The synthesis and secretion of lipoproteins particularly apoB containing lipoproteins by primary cultures of hepatocytes from these rats were studied by 14(C)-acetate or 3(H)-leucine labelling. Primary cultures of hepatocytes derived from sardine oil-fed rats showed reduced incorporation of 3(H)-leucine into apoB containing lipoproteins secreted into the medium when compared to those fed groundnut oil, indicating a decreased synthesis and secretion of apoB. This was further confirmed by significantly lower incorporation of 14(C)-radioactivity into total and individual lipids of VLDL secreted into the medium, as well as that associated with different lipids in cell layer. The activity of lipoprotein lipase in adipose tissue and aorta was significantly higher in rats fed sardine oil which may cause an increased clearance of triglyceride-rich lipoproteins from circulation. These results indicate that the fish oil exerts hypolipidemic effect particularly by decreasing the synthesis and secretion of VLDL by liver and possibly by an increased clearance of triglyceride-rich lipoproteins from circulation. PMID- 1506037 TI - Albumins enhance motility of sperm of spotted Indian house gecko Hemidactylus brooki (Gray). PMID- 1506036 TI - Antidiabetic effects of S-allyl cysteine sulphoxide isolated from garlic Allium sativum Linn. AB - S-allyl cysteine sulphoxide (SACS), a sulphur containing amino acid of garlic which is the precursor of allicin and garlic oil, has been found to show significant antidiabetic effects in alloxan diabetic rats. Administration of it at a dose of 200 mg/kg body weight decreased significantly the concentration of serum lipids, blood glucose and activities of serum enzymes like alkaline phosphatase, acid phosphatase and lactate dehydrogenase and liver glucose-6 phosphatase. It increased significantly liver and intestinal HMG CoA reductase activity and liver hexokinase activity. PMID- 1506038 TI - Antifertility activity of seed of Nelumbo nucifera in mice. PMID- 1506039 TI - Control of zoopathogenic fungi in vitro by polyamine biosynthesis inhibitors. AB - Effect of inhibitors of polyamine (PA) biosynthesis, alpha difluoromethylornithine (DFMO), methylglyoxal bis (guanylhydrazone)--MGBG and bis (cyclohexylammonium) sulphate (BCHA) on mycelial growth of three clinically important fungi-Trichophyton mentagrophytes, Microsporum gypseum and Aspergillus flavus was examined in vitro. All inhibitors at concentrations 1 to 50 mM produced greater inhibition of mycelial growth in all fungi tested in a dose dependent manner. MGBG was the most effective inhibitor, and T. mentagrophytes was the most sensitive fungus to all inhibitors followed by M. gypseum and A. flavus. The results suggested that control of fungal diseases in animals and human beings with specific inhibitors of PA biosynthesis is possible. PMID- 1506040 TI - Toxicity of dimethoate on urinary hydroxyproline in rats. AB - The effect of the administration of three different concentrations (2.25, 1.13 and 0.56 mg/100 g body weight) of dimethoate on the urinary excretion of total, non dialysable and free hydroxyproline were studied in female albino rats. Compared to controls, the urine contents were significantly lower in higher concentration (2.25 mg/100 g body weight) of dimethoate treated rats. The results clearly indicate that the urine contents were not much affected in lower concentration (0.56 mg/100 g body weight) of dimethoate treated rats compared to the other concentrations (1.13 and 0.56 mg/100 g body weight) of dimethoate treated rats. PMID- 1506041 TI - Antifilarial activity of Centratherum anthelminticum seed extracts on Setaria cervi. AB - Effect of aqueous and alcoholic extract of C. anthelminticum was studied on the spontaneous movements of the whole worm and nerve-muscle preparation of S. cervi. Ethylacetate, acetone and methanol extract showed similar effect, of causing inhibition of spontaneous motility of the nerve-muscle preparation of S. cervi characterized by decreased amplitude and frequency of contractions. The inhibitory effect on the motility was reversible. Further, the extracts did not involve the blockade of cholinergic receptors as evidenced by the presence of unaltered stimulant response of acetylcholine in the presence of drug in bathing fluid. PMID- 1506042 TI - Detection of autoreactive antibodies to serum IgG and IgA in amoebic liver abscess cases. AB - Assessment of autoreactive antibodies in response to healthy human serum IgA and IgG was performed by indirect haemagglutination assay on serum samples from 81 amoebic liver abscess cases for IgA and 70 for IgG. Appropriate controls were taken simultaneously. IgA, IgG were isolated and purified from a healthy human serum through Sephadex G-200 and protein A CL 4B sepharose chromatography. These immunoglobulins were used for the detection of its own antibodies in amoebic liver abscess cases. This revealed that 43.20% and 48.50% of the cases were positive for IgA and IgG respectively, where as only 19.35% and 28.30% of the controls were in positive category (IgA and IgG respectively). The mean titres with standard deviation of the autoreactive antibodies to serum IgA both in ALA cases and controls shows a highly significant difference between tests and controls (P less than 0.001). Similarly the mean titres with standard deviation both in ALA and controls for the serum IgG differed significantly (P less than 0.001). This suggests the presence of autoreactive antibodies against serum IgA and IgG in amoebic liver abscess cases. PMID- 1506043 TI - Effect of aspirin on serum lipoprotein profile in rats subjected to myocardial stress by isoproterenol. AB - The effect of isoproterenol on the levels of serum lipoprotein profile were studied in rats. Rats were treated with isoproterenol (200 mg/100 g body weight, sc twice at an interval of 24 hr) for 2 days. Aspirin was administered orally 1.2 mg/100 g body weight, daily for 60 days. Isoproterenol treated rats showed decrease in the activities of hepatic and extrahepatic lipoprotein lipase. HDL cholesterol level was found to be decreased, significantly with increase in LDL cholesterol in isoproterenol treated rats. Aspirin treated rats showed marked reversal of these metabolic changes. The lipoprotein changes were minimum in rats treated with both aspirin and isoproterenol. PMID- 1506044 TI - Hepatitis E: does person-to-person spread occur? PMID- 1506045 TI - Hepatitis E: evidence for person-to-person transmission and inability of low dose immune serum globulin from an Indian source to prevent it. AB - This study was undertaken to assess the role of person-to-person transmission in hepatitis E and the ability of immune serum globulin (ISG) from an Indian source to prevent such transmission. Seventy six subjects (62 household contacts of patients with sporadic hepatitis E and 14 controls with no household contacts) were studied clinically, biochemically and serologically at entry and fortnightly thereafter for the next 8 weeks. Thirty two household contacts received 2 mL of 16.5% ISG 16.5% while the other 30 household contacts and 14 controls received 2 mL of normal saline intramuscularly at entry. Eighteen (29%) household contacts and none of the control subjects developed biochemical evidence of acute hepatitis E (p less than 0.01). The enzyme elevation occurred after a mean interval of 31.0 +/- 4.5 days from the onset of disease in the index case. This suggested that the disease in the case contacts had been contracted by household contact with the index case and not by simultaneous infection of the index case and the household contact. The incidence of disease was similar in the household contacts receiving ISG and normal saline (25% and 33.3% respectively, p = ns). ISG had no effect on the time interval to SGPT rise or on the severity of disease in household contacts. PMID- 1506046 TI - Hepatic lesions caused by excretory and secretory products of Ascaris lumbricoides in golden hamster. AB - OBJECTIVE: To ascertain the role of excretory and secretory (ES) products of Ascaris lumbricoides in liver damage. METHODS: The ES products of A lumbricoides were collected in vitro and their SDS-PAGE analysis was done. Feeding and subcutaneous injection of ES products were done in hamsters. Estimation of serum proteins, alkaline phosphatase and alanine aminotransferase and histology of liver were carried out. Control animal experiments were done concurrently. RESULTS: The ES products of A lumbricoides contained several proteins ranging in molecular weight from 14 to 205 Kd. Prolonged feeding of ES products caused elevation of ALT and amyloid deposition in the liver, whereas short term feeding or subcutaneous challenge caused focal cell necrosis and granuloma formation in the liver. CONCLUSION: ES products of A lumbricoides can produce liver damage. PMID- 1506047 TI - Evaluation of radical treatment of carcinoma esophagus using a combination of external beam and intracavitary irradiation. AB - Twenty five patients with squamous cell carcinoma arising from the middle third of the esophagus were treated radically, with external radiation, to a dose of 55 60 Gy. All patients had lesions less than 6 cm in length with no extra-esophageal spread on computed tomography scan. Eleven of these patients received additional intracavitary radiation to a dose of 12 Gy, 1 cm from the source axis in two sessions of 6 Gy each, a week apart. There was no significant difference in the relief of dysphagia and survival among these receiving and those not receiving intracavitary radiation. Addition of intracavitary radiation to radical external radiation was associated with significant complications like stricture and fistulae formation, which accounted for the poor results. PMID- 1506048 TI - A prospective study of radiation induced damage of pancreatic ducts. AB - To study radiation-induced pancreatic duct damage, endoscopic retrograde pancreatograms of 11 patients with primary gastric lymphoma who had completed chemotherapy and moderate dose external radiation therapy were compared with those of 22 normal subjects. No significant alteration was seen in the length and caliber of the main pancreatic duct and number of side branches. Clubbing of one or two side branches was observed in four patients who had received radiation (p = ns). We conclude that significant structural changes do not develop in the pancreas following moderate dose upper abdominal radiation. PMID- 1506049 TI - Evaluation of peritoneovenous shunt in refractory cirrhotic ascites in Indian patients. AB - Ten patients with tense and refractory cirrhotic ascites underwent a modified peritoneovenous shunt procedure. Nine patients responded with complete resolution of ascites, mean weight gain of 5 (range 0-8) Kg, and rise in serum albumin level of 0.6 g/dL. Six patients improved from Child's class B to A. The longest survival period was 2.3 years. The main constraint in a developing country is the high cost of the shunt. PMID- 1506050 TI - Nutrition in critically ill cancer patients. PMID- 1506051 TI - Symptomatic solitary giant congenital cysts of liver. AB - Three cases of non-parasitic liver cysts are reported. Each of them presented with upper abdominal pain and enlarged liver, and a cyst of enormous size was detected by ultrasound and isotopic scan. Residual cavity following cyst surgery was obliterated by different surgical techniques. PMID- 1506052 TI - Transient achalasia of esophagus in tetanus. AB - A case with tetanus presenting with progressive dysphagia due to lower esophageal dysfunction is described. A barium swallow at the onset of symptoms showed esophageal dilatation with a smooth tapering at the lower end suggestive of achalasia cardia. The patient recovered from tetanus over the ensuing three weeks; repeat barium swallow at this time was normal, suggesting that esophageal dysfunction was a manifestation of tetanus. PMID- 1506053 TI - Explosive Campylobacter jejuni diarrhea in immunoproliferative small intestinal disease. AB - Campylobacter jejuni is an infrequent cause of self limiting acute diarrheal disease in adults in the Indian subcontinent. We report the occurrence of a life threatening diarrhea due to C jejuni infection in a patient with immunoproliferative small intestinal disease. We postulate that immunosuppression due to malignancy, malnutrition and cancer chemotherapy was responsible for the unusually severe diarrhea. PMID- 1506054 TI - Organoaxial volvulus of the stomach following corrective surgery for gastric outlet obstruction. AB - We report an unusual complication following vagotomy and pyloroplasty for chronic gastric outlet obstruction. Persistence of increased gastric aspirate led to the diagnosis of organoaxial volvulus of the stomach on barium studies. We postulate that laxity of the gastric suspensory ligaments after gastric decompression and postoperative adhesion were responsible for its development. PMID- 1506055 TI - Helicobacter pylori in north Indian subjects. PMID- 1506056 TI - Management of bottle cap ingestion. PMID- 1506057 TI - Microlithiasis and acute pancreatitis. PMID- 1506058 TI - Susceptibility of south Indian strains of Mycobacterium tuberculosis to tuberactinomycin. AB - A total of 114 strains of Mycobacterium tuberculosis isolated from sputum samples of 114 patients of pulmonary tuberculosis in south India, were coded and tested for their in vitro susceptibility to tuberactinomycin (Tum) incorporated in Lowenstein-Jensen (LJ) medium. Of these strains, 95 (83.3%) and 15 (13.2%) were susceptible to Tum at 25 and 50 mg/l respectively. Only 4 (3.5%) strains were inhibited at 100 mg/l or more. Of the 37 drug sensitive strains, 2 (5.4%) were not susceptible to Tum at 25 mg/l compared to 17 (22.1%) of 77 strains-resistant to one or more of antituberculosis drugs (P less than 0.02). The drug susceptibility pattern of the strains revealed that there was no significant association of resistance between Tum and streptomycin or rifampicin or ethambutol or ethionamide or isoniazid. However, 15 (53.6%) of 28 kanamycin (K) resistant strains were not susceptible to Tum at 25 mg/l. This cross resistance between Tum and K was further studied in 24 and 15 K sensitive and resistant strains respectively, by correlating their proportion resistance at 16 mg/l and it was found to have a significant positive correlation (r = 0.55; P less than 0.01). PMID- 1506059 TI - Filter paper blood spot test for detection of anti-ND-BSA antibodies in school children. AB - For identifying individuals at 'high risk' for developing leprosy, a simplified technique of collection of blood samples on filter paper for detection of anti ND-BSA antibodies, was optimised. Anti-ND-BSA antibody reactivity on the filter paper was lost on storage at room temperature, but was stable at least for a period of 8 wk at lower temperature. Among the 1495 children screened, 166 (11.1%) were lepromin negative and 122 (8.2%) positive for anti-ND-BSA antibody. In the first phase, 7 of 871 children followed up for 2 yr developed leprosy, while in the second phase 2 of 624 children followed-up for 9 yr developed leprosy. The positivity and negativity of anti-ND-BSA antibodies and lepromin in these I children indicate that the positive status for anti-ND-BSA antibodies has a better predictive value than negative lepromin reactivity. Measurement of anti ND-BSA antibodies was also of value for monitoring the efficacy of therapy and course of the disease. Extrapolation of the two tests to the total population of children evaluated showed that an individual with negative lepromin reactivity along with presence of anti-ND-BSA antibodies is at a higher risk for developing leprosy than those who have both the tests normal. Lepromin reactivity alone was not of much value for the prediction for development of the disease. However, the presence of anti-ND-BSA antibody was a better indicator for the development of the disease. The probability of developing leprosy in a child with any one of the tests abnormal was higher as compared to a child having all the tests normal. PMID- 1506060 TI - Nonradioactive polynucleotide gene probe assay for the detection of three virulence toxin genes in diarrhoeal stools. AB - The present study describes a nonisotopic DNA-DNA hybridization assay for the detection of enterotoxigenic Escherichia coli (ETEC) in which the probes were labelled with the hapten molecule digoxigenin and after hybridization, DNA hybrids were detected by antidigoxigenin alkaline phosphatase conjugate. A blinded study carried out on a battery of enterotoxigenic and nonenterotoxigenic Esch. coli by dig-probe hybridization assay were compared with the results of a radiolabelled toxin gene probe hybridization assay (performed earlier). The three digoxigenin labelled probes gave a 100 per cent specificity and sensitivities of 95.45, 100 and 100 per cent for LT, STh and STp respectively. These results were comparable to those with the radioactive probes. PMID- 1506061 TI - Serovar, biotype, phage type, toxigenicity & antibiotic susceptibility patterns of Vibrio cholerae isolated during two consecutive cholera seasons (1989-90) in Calcutta. AB - Characteristics of V. cholerae isolated from patients of acute secretory diarrhoea admitted to the Infectious Diseases Hospital, Calcutta during two consecutive cholera seasons (1989 and 1990), with special emphasis on biotyping and toxigenicity, were investigated. The isolation rates of V. cholerae during 1989 and 1990 were 78 and 85.1 per cent respectively, with Inaba serotype dominating in 1989 and Ogawa in 1990. All the V. cholerae 01 strains isolated in this study belonged to biotype Eltor with phage type 4 dominating (48.8%). Most of the strains of V. cholerae were resistant to 10 and 150 micrograms/ml of 0/129 vibriostatic agent. Similarly, majority of the V. cholerae strains were resistant to furazolidone (95.7%), cotrimoxazole (83%) and tetracycline (63.1%) and several resistance patterns were encountered. All the V. cholerae 01 strains examined produced cholera toxin (CT) in amounts ranging between greater than 70 pg/ml and greater than 2.5 ng/ml. In contrast, all but one of the non-01 strains isolated in this study did not produce CT. Further studies are required to elucidate the mechanism involved in the pathogenesis of non-01 V. cholerae mediated diarrhoea. PMID- 1506062 TI - Biological characterisation of group F streptococci causing human infections. AB - Fifty five strains of group F streptococci (GFS) isolated from clinical samples of 53 patients with diverse diseases, were characterised by a battery of physiological tests. Among them 37 (67%) were Streptococcus anginosus F, 14 (25%) were Strep. intermedius, two of which were mannitol positive and 4 (7%) were Strep. constellatus. Determination of minimum inhibitory concentrations of penicillin, erythromycin, ampicillin, gentamicin and cefazolin showed that despite their biochemical heterogeneity, all strains were uniformly susceptible to these antibiotics. Except for bacteraemia, other diseases due to GFS responded well to surgical drainage and/or antibiotics. PMID- 1506063 TI - Comparative efficacy of fluoroquinolones, aminoglycosides, ureidopenicillins & newer cephalosporins against Pseudomonas species. AB - A total of 74 strains of Pseudomonas aeruginosa and 18 strains of Ps. putrefaciens were tested for sensitivity to 14 different antimicrobial agents. Ps. aeruginosa were mostly sensitive to netilmicin (81%), piperacillin (78%), amikacin (73%), azlocillin (70%), ceftazidime (69%) and pefloxacin (65%). Only 66 per cent strains of Ps. putrefaciens were sensitive to netilmicin, ceftazidime and ceftriaxone. The MIC values of the different drugs for the sensitive strains were comparable with the results of susceptibility testing. The Ps. putrefaciens strains showed greater resistance than Ps. aeruginosa. PMID- 1506064 TI - Role of Chlamydia trachomatis infections in infertility due to tubal factor. AB - The prevalence of IgG antibodies to C. trachomatis was determined in 185 infertile women who underwent laparoscopy, and 110 pregnant women with no known infertility problems. In addition, chlamydial antigens were evaluated by EIA in cervical samples taken from all subjects. Subjects with tubal infertility had the highest prevalence of chlamydial antigen and antibody (P less than 0.01). While the percentage of subjects with antigen and antibody positive was 11.6 per cent, those with antigen negative and antibody positive averaged 55.8 per cent among women with tubal related infertility. The results of our study provide additional support to the concept that infertility of tubal etiology often is a sequela of a previous chlamydial infection. PMID- 1506065 TI - Mycoplasma hominis in women with bacterial vaginosis. AB - An association between M. hominis and bacterial vaginosis (BV) was looked for in total 205 women characterized as having BV. Vaginal specimens from these patients were studied for the presence of amines, polymorphonuclear leukocytes, clue cells, and lactobacilli, and were also cultured to isolate Gardnerella vaginalis, M. hominis, Trichomonas vaginalis, Candida albicans and anaerobes. G. vaginalis was found to be the most common isolate from 132 cases (64.3%). M. hominis was isolated from 90 cases (43.9%). 62 per cent of M. hominis isolates were associated with G. vaginalis. 100 age matched control group revealed low prevalence of G. vaginalis and M. hominis whereas the difference in isolation rate of anaerobes was not significant. Anaerobes were found in association with M. hominis in 40 per cent cases. The treatment of these patients was decided after knowing the etiological agent. PMID- 1506066 TI - Bacteriology of ophthalmic infections with special reference to anaerobes. AB - A total of 138 eye specimens were processed for aerobic and anaerobic cultures. Clinical data were obtained from 50 patients with unilateral ophthalmic infection. Cultures from the uninfected eye of 38 of these 50 patients were also processed for comparison. In addition, 50 cultures were obtained from one or both eyes of 30 healthy controls who had no eye infection. Anaerobes and aerobes were isolated from infected eyes of 6 (12%) and 37 (74%) patients respectively. No growth was observed in infected eye of 8 (16%) patients. A mixture of aerobes and anaerobes were recovered only in 2 cases. Of the total 47 aerobic isolates from infected eye specimens, Staphylococcus aureus (11), coagulase negative staphylococci (12) and Streptococcus pneumoniae (9) were predominant isolates. Six anaerobes isolates included Gram positive nonsporing anaerobic bacilli (4 including Propionibacterium acne) as predominant isolates. Clostridium perfringens was isolated from a case of post operative endoophthalmitis. From the uninfected eye of same patients though the number and types of aerobic bacteria were similar, none grew any anaerobes. Aerobic and anaerobic bacteria were isolated in 70 and 6 per cent of eye swabs respectively from the healthy controls. PMID- 1506067 TI - Dermatonecrotic lesions in rabbits caused by neuraminidase. AB - In an attempt to study the role of neuraminidase in cholera vibrio pathogenesis, the dermatonecrotic effect of a purified neuraminidase preparation was studied in rabbits. The experiments demonstrated that dermatonecrotic lesions resulted from intracutaneous injection of a purified neuraminidase preparation (0.5 specific human dose or 1 NU) as well as significant doses of cholera toxoid containing the enzyme (4,12,18 specific human doses). PMID- 1506068 TI - A cost benefit analysis of fish culture strategy towards the control of mansonioides in Shertallai, Kerala state. AB - The cost benefit analysis of fish culture as a means for vector control towards the containment of Brugian filariasis in Shertallai, a highly endemic tract for this disease in Kerala was carried out. While the financial gain accrued to the community was to the tune of Rs. 1,82,052 in ponds (under monoculture) with Chinese grass carp from 763 ponds, it was Rs. 1,83,740 from 1000 ponds under polyculture with Catla catla, Cyprinus carpio, Labeo rohita, Labeo fimbriatus, Cirrhina mrigala and Ctenopharyngodon idella (Chinese grass carp). Monoculture with Giant gourami (Osphronemous goramy) fetched an income of Rs. 7,654 to the community from 128 ponds. A marked reduction in weed reinfestation/vector breeding was observed in ponds under fish culture than other without fishes. The study clearly indicates that fish culture is an ideal strategy for Mansonioides control as it can bring perceptible benefits to the community. PMID- 1506069 TI - Septal polydipsia in rats is a primary polydipsia not mediated by dopamine. AB - Bilateral lesions of nucleus septal lateralis resulted in a sustained and significant increase in water intake, without any change in food intake. Intracerebral injection of dopamine (DA) or of spiperone (a central D2-receptor antagonist) did not elicit any change in water or food intake. The polydipsia resulting from septal lesions is thus a primary polydipsia, which is independent of food intake, and is not mediated by neurotransmitter dopamine. PMID- 1506070 TI - Effect of short term 'Pranayam' practice on breathing rate and ventilatory functions of lung. AB - Thirty three normal male and forty two normal female subjects, of average age of 18.5 years, underwent six weeks course in 'Pranayam' and their ventilatory lung functions were studied before and after this practice. They had improved ventilatory functions in the form of lowered respiratory rate (RR), and increases in the forced vital capacity (FVC), forced expiratory volume at the end of 1st second (FEV1%), maximum voluntary ventilation (MVV), peak expiratory flow rate (PEFR-lit/sec), and prolongation of breath holding time. PMID- 1506071 TI - Effect of short term administration of Tulsi (Ocimum sanctum Linn.) on reproductive behaviour of adult male rats. AB - Effect of feeding Tulsi leaves along with the normal diet, on the reproductory behaviour of adult male Wistar rats, was studied. Experimental animals were given Tulsi extract in graded doses of 100 mg/kg, 150 mg/kg, 200 mg/kg, and 400 mg/kg along with the normal diet while control group only had similar normal diet. Each dose was given for 15 days and reproductory behaviour monitored in terms of score, on every alternative day. There was significant decrease in sexual behavioural score, when Tulsi leaves extract dose was increased to 200 mg/kg and 400 mg/kg. PMID- 1506072 TI - Pharmacokinetics of oxytetracycline in presence of calcium gluconate in goats. AB - The concentration of oxytetracycline (OTC) in plasma, after single dose i.v. administration at 10 mg kg-1, was determined during pre and post induced hypercalcemia in goats. The pharmacokinetic variables were then calculated. Hypercalcemia caused several changes in the determined variables. The CPmax and CPmin of OTC observed at 0.08 and 4 hr in normal goats were respectively 34.50 +/ 1.65 and 1.19 +/- 0.14 micrograms ml-1, while the CPmax and CPmin of OTC in presence of calcium at 0.08 and 8 hr were 20.81 +/- 2.18 and 1.04 +/- 0.05 micrograms ml-1 respectively. Hypercalcemic state in goats increased t1/2 (alpha) (0.19 +/- 0.02 hr), t1/2 (beta) (2.77 +/- 0.03 hr), AUC (37.67 +/- 0.83 micrograms x hr x ml vd (area) (1.07 +/- 0.03 L kg-1) and vd (ss) (0.95 +/- 0.04 L kg-1) values of OTC compared to normal goats. The semilogarithmic plot of plasma level-time profile of OTC administered i.v. showed biphasic decline suggestive of two compartment open model 'kinetics' in both normal and hypercalcemic animals. PMID- 1506073 TI - Blood basopenia as an indicator of ovulation. AB - Direct basophil counts were done on capillary blood samples in thirteen normal young women, during the different phases of their menstrual cycles. Mean basophil counts during the follicular and progestational phases were 36.6/cumm and 39.3/cumm respectively. A significant midcycle fall in counts of 36% and a premenstrual fall of 22% were observed. These changes are probably due to migration of the cells from the peripheral blood into the rupturing follicle of the ovary and into the ischemic premenstrual endometrium. PMID- 1506074 TI - Peak expiratory flow rate in adolescent male swimmers of all India rural swimming meet. AB - Peak expiratory flow rate (PEFR), an important test to assess overall lung function, was determined in 84 male adolescent subjects, out of which there were 46 and 38 nonswimmers (NS). Their ages varied between 9 to 15 years. It was observed that a significant spurt in PEFR value occurs in S at the age of 12 years. A similar spurt in growth (height & weight) in S, not so apparent in NS, was also observed at the same age period. The enhanced growth was recorded in S at all age groups in comparison with those of NS. It was further observed that with increase of height, the PEFR also increased in both the groups however significant by higher values (P less than 0.05) were obtained in S, as compared with NS having the same height. PMID- 1506075 TI - Evaluation of anxiety status in medical students prior to examination stress. AB - Pulse rate (PR), blood pressure (BP), auditory reaction time (ART), galvanic skin resistance (GSR), and eosinophil count (EC) were determined in 30 male and 25 female medical students appearing for the I MBBS viva-voce examination. Two readings were taken viz 2 months (control) and 20 min prior to the examination. A statistically significant increase was seen in the PR and BP while a significant decrease was observed in ART, GSR and EC before the examination as compared to the control readings. There was a significant correlation between the PR and ART. PMID- 1506076 TI - Immunotoxic responses of cypermethrin, a synthetic pyrethroid insecticide in rats. AB - The study was undertaken to evaluate immunotoxic effects of cypermethrin administered orally (in ground nut oil) to male albino rats at dose levels (mg/kg) of 0 (control), 5, 10, 20 and 40 once daily for 90 days. Cypermethrin administration produced a significant leucopenia at 40 mg/kg on day 90. A dose dependent decrease (P greater than 0.05) in delayed type hypersensitivity reaction was noticed on day 61 post treatment. Humoral response as evidenced by serum haemagglutinin and haemolysin titres did not show any definite pattern on day 90. However, a significant decrease in spleen weights and significant increase in adrenal weights was recorded in rats receiving the highest test level. Total body weights and liver weights did not show any significant change with any of the dose level studied. Results of the study reveal that low doses (5 and 10 mg/kg) did not have any adverse effect on the immuno-competence of rats. PMID- 1506077 TI - Comparison of the protective effect of Withaferin-'A' and hydrocortisone against CCL4 induced hepatotoxicity in rats. AB - Protective effect of Withaferin-'A' against CCl4 induced hepatotoxicity has been assessed and the compound at 10 mg/kg dose was found to possess significant protective effect. A comparison of this protective effect with that of hydrocortisone showed it to be as effective as hydrocortisone dose per dose. PMID- 1506078 TI - Aggravating action of hydralazine on ethanol-induced gastric lesions. AB - Endogenous nitric oxide has been proposed as one of the mediators of gastric cytoprotection. We studied the effect of the vasodilator hydralazine which acts via nitric oxide and thus is expected to have a gastroprotective action. However, hydralazine aggravates ethanol-induced gastric lesions. This effect is not influenced by pretreatment with the selective alpha 1 adrenergic antagonist prazosin but is abolished by the angiotensin converting enzyme inhibitor, captopril suggesting the involvement of the renin-angiotensin system. PMID- 1506079 TI - Failure to reduce experimental myocardial infarct size with ibuprofen pre treatment in rats. AB - The prophylactic role of ibuprofen in experimental myocardial infarction has not been reported. Twenty-four rats pre-treated with ibuprofen (30 mg/kg), po, for 21 days were subjected to myocardial infarction by administration of isoprenaline hydrochloride (85 mg/kg), sc, on two consecutive days. An equal number of rats were given saline to serve as control. Heart specimens were taken for macroscopic and microscopic examination after 1 day, 5 days, 12 days and 21 days, following myocardial infarction. Ibuprofen pre-treatment caused a significant increase in infarct size at all the intervals studied (P less than 0.01), indicating that ibuprofen exerted a harmful effect in increasing the size of experimental myocardial infarction. PMID- 1506080 TI - Changes in cognitive functions in epileptics on sodium valproate monotherapy. PMID- 1506081 TI - Effect of extract of leaves of Vinca rosea linn. on glucose utilization and glycogen deposition by isolated rat hemidiaphragm. PMID- 1506082 TI - Drug advertisements in Indian medical journals. PMID- 1506083 TI - Desired pupillary dilation achieved with a smaller drop volume of phenylephrine in rabbits. PMID- 1506084 TI - An assessment of clinical trials with drugs. PMID- 1506086 TI - Physiology: a turning point. PMID- 1506085 TI - Sir Charles Scott Sherrington (1857-1952) PMID- 1506087 TI - Evaluation of semen quality in a local Libyan population. AB - Semen analyses was carried out in a population of 1250 randomly selected Libyan males. Two semen samples collected from each volunteer were subjected to the routine analyses following the World Health Organization recommendations. The Libyan population had a higher percentage of men with sperm density in the range of 40-60 millions/ml. The percentage of men with sperm counts above 100 millions/ml is comparatively lower than that is reported by MacLeod and Gold (9). The seminal plasma transferrin levels showed a positive correlation with sperm density and alpha-glucosidase activity with sperm motility. PMID- 1506088 TI - Effect of Santhi Kriya on certain psychophysiological parameters: a preliminary study. AB - Santhi Kriya is a mixture of combined yogic practices of breathing and relaxation. Preliminary attempts were made to determine the effect of Santhi Kriya on certain psychophysiological parameters. Eight healthy male volunteers of the age group 25.9 +/- 3 (SD) years were subjected to Santhi Kriya practice daily for 50 minutes for 30 days. The volunteer's body weight, blood pressure, oral temperature, pulse rate, respiration, ECG and EEG were recorded before and after the practice on the 1st day and subsequently on 10th, 20th and 30th day of their practice. They were also given a perceptual acuity test to know their cognitive level on the 1st day and also at the end of the study i.e., on the 30th day. Results indicate a gradual and significant decrease in the body weight from 1st to 30th day (P less than 0.001) and an increase in alpha activity of the brain (P less than 0.001) during the course of 30 days of Santhi Kriya practice. Increase of alpha activity both in occipital and pre-frontal areas of both the hemispheres of the brain denotes an increase of calmness. This study also revealed that Santhi Kriya practice increases oral temperature by 3 degrees F and decreases respiratory rate significantly (P less than 0.05) on all practice days. Other parameters were not found to be altered significantly. It is concluded that the Santhi Kriya practice for 30 days reduces body weight and increases calmness. PMID- 1506089 TI - Effect of dothiepin on nociceptive response in diabetic rats. AB - In alloxan-diabetic rats of 4 wk duration with blood glucose levels of about 300 mg/100 ml, the tail flick reaction time (TFRT) to thermal stimuli was significantly elevated (P less than 0.25), indicating hypoalgesia. Intraperitoneal dothiepin, injections of 25 mg & 50 mg/kg body weight per day did not significantly alter the TFRT, either in control or in diabetic rats, following either acute (one dose), or short term (once a day for five days) administration. It is concluded that at least in the dosage schedule used herein, dothiepin does not influence hypoalgesia of diabetic neuropathy. PMID- 1506090 TI - Biochemical and pathological changes in response to hyperoxia and protection by antioxidants in rats. AB - A significant decrease in blood haemoglobin, reduced glutathione and protein in lung and liver, without any change in blood reduced glutathione, was observed in rats exposed to 80% oxygen. Hydrogen peroxide induced erythrocyte haemolysis was significantly increased following exposure to hyperoxia. The lungs of rats exposed to hyperoxia showed perivascular edema. Simultaneous treatment with antioxidants, vitamin A, C, or E, protected the animals against oxygen toxicity. PMID- 1506091 TI - Present day concept of non-invasive imaging. PMID- 1506092 TI - Cranial sonography in preterm infants. AB - Fifty preterm newborn infants with gestational age of 28-36 weeks were subjected to real time cranial sonography to (a) evaluate the ventricular system and brain parenchyma, (b) determine the incidence of intracranial abnormalities, and (c) to establish the utility and advantages of routine cranial sonography in preterm infants. The lateral ventricular width varied from 6-12 mm (8.67 +/- 1.85 mm) while hemispheric width ranged between 3.68 to 3.95 cm with a mean of 3.84 +/- 0.25 cm. The lateral ventricular ratio ranged from 20.9 to 26.4% and it showed progressive decrease with increasing gestational age. Cavum septum pellucidum was found in 68% of the preterms. Incidental intracranial pathologies were detected in 12% of the preterms screened. PMID- 1506094 TI - Normal ventricular size and ventriculo-hemispheric ratio in infants upto 6 months of age by cranial ultrasonography. AB - Fifty cases each of preterm (greater than 34 weeks), full term and one month to six months age (400 total) were subjected to cranial ultrasonography for determination of ventricular size and ventriculohemispheric ratio. Ventricular size steadily increased from 4.64 +/- 1.84 mm in preterm to 10.72 +/- 2.92 mm in six months old infant. Ventriculohemispheric ratio increased from 0.12 +/- 0.052 in preterm to 0.17 +/- 0.056 in three months of age. Then steady level was maintained at 0.17 +/- 0.064 upto six months of age. PMID- 1506093 TI - Role of ultrasound guided percutaneous antegrade pyelography (USPCAP) in the diagnosis of obstructive uropathy. AB - Ultrasound guided percutaneous antegrade pyelography (USPCAP) was performed in 6 cases between 1 month and 8 years age, presenting with obstructive uropathy. The procedure in this age group was characterized by (i) ease of performance without sedation in the neonates and with sedation in older children, and (ii) use of smaller needles and catheters. The procedure enabled delineation of the intimate anatomy of complicated urological abnormalities such as obstructed duplex system, primary megaureters, posterior urethral valves, prune belly syndrome, obstructive hydronephrosis and vesicoureteric reflux. Percutaneous renal puncture may be established rapidly using ultrasonic guidance in severely ill pediatric patients with obstructive uropathy. B-mode ultrasonography has proved to be rapid, accurate and free of radiation hazards, making it applicable to children with little or no sedation. Guided by ultrasound, percutaneous antegrade pyelography should be considered in the few, selected children with obstructive uropathy when the diagnosis is critical for management and difficult with the usual imaging procedures. PMID- 1506095 TI - Multidrug resistant typhoid fever: therapeutic considerations. AB - Forty six blood culture positive cases were studied during the current outbreak of multidrug resistant typhoid fever (MRTF). The present outbreak was caused by E1 phage type and organisms were resistant to all commonly used drugs for the treatment of typhoid fever, viz., chloramphenicol (78%), co-trimoxazole (76%) and ampicillin (68%). Treatment failures with chloramphenicol (45.5%) corroborated well with in vitro resistance. No treatment failure was seen with chloramphenicol and ceftriaxone, when these drugs were used in cases infected with sensitive strains. Among the alternative drugs used in cases with in vitro sensitivity, successful clinical response was seen with ceftriaxone (4/4) and cefotaxime (8/9) as compared to cephalexin (3/5) or a combination of cephalexin and furazolidone (9/12). PMID- 1506096 TI - Assessment of newborn baby's temperature by human touch: a potentially useful primary care strategy. AB - Fifty healthy term neonates delivered at All India Institute of Medical Sciences Hospital were assessed by three pediatricians for skin temperature to the nearest +/- 0.5 degrees C at the three body sites, i.e., mid-forehead, abdomen and dorsum of right foot by touch. The predicted temperatures at different sites were compared with simultaneously recorded temperatures at the same sites with the help of an electronic thermometer having a sensitivity of +/- 0.1 degree C. Rectal temperature was also recorded in all the babies with a rectal thermister to compare the variations between the core and skin temperatures. There was a good correlation between the skin temperatures of the babies as perceived by touch and values recorded with the help of an electronic thermometer. All the hypothermic babies were correctly picked up by all the observers. There was good correlation between core temperature and skin temperature at different sites except forehead. It is amazing that even during the month of May, when ambient temperature was maintained between 26-28 degrees C, nearly one fifth of the healthy term babies were under cold stress as evidenced by greater than 2 degrees C difference between the core and peripheral skin temperatures. It is recommended that health professionals and mothers should be explained the importance of evaluating the core and peripheral skin temperature by touch for early identification of babies under cold stress in order to prevent occurrence of life threatening hypothermia. PMID- 1506097 TI - Exchange transfusions via peripheral vessels. AB - During a 15 month period, partial exchange transfusions (ET) were done in 40 neonates with polycythemia, and double volume ET attempted in 7 neonates with hyperbilirubinemia via peripheral vessels. The procedure was effective and not associated with any complications for partial ET. During double volume ET minor complications were noted in 2 cases, both of whom recovered and subsequently successfully underwent supraumbilical ET. Of the 5 cases who had uneventful double volume exchanges, there was a significant drop in indirect serum bilirubin following the procedure. The mean pre-ET serum indirect bilirubin in these 5 cases was 334 mumol/L and mean post-ET level was 179 mumol/L with a mean drop of 155 mumol/L (46% drop). Technical difficulties in catheterization may be overcome with greater expertise and use of heparin to flush arterial catheters. PMID- 1506098 TI - Stool electrolytes in acute dehydrating gastroenteritis. AB - Stool electrolytes were studied in 100 cases of gastroenteritis. The duration of illness was 24-48 hours in 32% and 72-96 hours in 28% of the cases. On stool culture, 43% children had no growth, 23% had Enteropathogenic E. coli and 10% had cholera and rotavirus each. The stool sodium loss was more in cholera and shigella cases, diarrhea of shorter duration and in children between 24-30 months of age. Potassium loss in the stool was more in shiegella cases, diarrhea of short duration and in children between 30-36 months of age. In cases of gastroenteritis with severe malnutrition, stool sodium loss was less; stool potassium loss was not affected by the nutritional status. Total electrolytes lost in stools can be estimated by knowing purging rate and rehydration therapy can be planned accordingly. PMID- 1506099 TI - Growth, behavior, development and intelligence in rural children between 1-3 years of life. AB - In a rural cohort of 625 children registered from 1981 to 1983 in 10 villages of K.V. Block, Varanasi, 196 children were assessed for physical growth, development, intelligence and concept development between 1 and 3 years of age. Home environment was also assessed using Caldwell Home inventory. These rural children remained below 3rd centile of NCHS standard for weight, height, skull and mid-arm circumferences throughout the study. Malnourished children scored poorly in all the areas of development, i.e., motor, adaptive, language and personal social, 9% in Grade I and 16.6% children in Grade II + III had IQ less than 79 (inferior). Concept for color shape and size was poorly developed in malnourished children. Maternal involvement and stimulation was strongly associated with better behavior development and intelligence. Multiple regression analysis showed that the effect of home environment on development and intelligence was of a higher magnitude as compared to status and family variables and nutritional status during 1-3 years of age. PMID- 1506100 TI - Comparative evaluation of calf, thigh and arm circumferences in detecting low birth weight infants--Part II. AB - In an earlier study usefulness and validity of calf circumference in the identification of low birth weight (LBW) infants was reported. To evolve a simple indicator in identifying LBW in community, comparative evaluation of three simple measurements, i.e., circumferences of calf (CC), thigh (TC) and arm (AC) was done with respect to their sensitivity and specificity. Though all the three measurements showed a high degree of correlation with the birth weight, calf circumference tended to be most sensitive in identifying almost 95% of LBW infants. Having established the superiority of CC, a two color tape demarcating LBW zone from normal birth weight using 10 cm CC as cut off point was tested by two independent investigators and two ANMs. It was observed that only 5% of cases were misclassified either as LBW or normal weight by the tape with hardly any inter individual variation. Measurement of calf circumference being simple and easy even in the hands of paramedics, it would be used as indicator of LBW and neonatal mortality in the community. PMID- 1506101 TI - Prenatal diagnosis of Meckel's syndrome. PMID- 1506102 TI - Antenatal diagnosis of acrania. PMID- 1506103 TI - Can health workers be trained in case detection of pneumonia? PMID- 1506104 TI - Hepatic manifestations in sickle cell disease. PMID- 1506105 TI - Facial hemiatrophy. PMID- 1506106 TI - Values for foot length in newborns. PMID- 1506107 TI - Gangrenous stomatitis following measles. PMID- 1506108 TI - Chylous mesenteric cyst: an unusual cause of neonatal intestinal obstruction. PMID- 1506109 TI - Third generation cephalosporins in multi-drug resistant typhoid fever. PMID- 1506110 TI - Danger of contrast enhanced CT scan. PMID- 1506111 TI - Ileocecal lymphoma presenting as an epigastric mass. PMID- 1506112 TI - Asymptomatic hematuria and proteinuria. PMID- 1506113 TI - Fever without focus. PMID- 1506114 TI - Do exclusively breast fed infants need fluid supplementation? PMID- 1506115 TI - The impact of methodological changes in gerontology. AB - The impact of methodological changes on gerontology is illustrated by discussing the example of the age-cohort-period problem as an innovation in research design, and examining the case of confirmatory factor analysis as an illustration of how methodological innovation informs theory. PMID- 1506116 TI - Generations and the generation of theory in social gerontology. AB - The process of theorizing, creating theoretical explanations, and disseminating theoretical perspectives is most frequently discussed in terms of disembodied ideas. A more insightful rendering of how theory is used in the sociology of aging literature would attend to the real individuals who promulgate the ideas. Looking at theorizing as a career-related activity engaged in by scholars who are prone to the same demographic imperatives as other human beings is a way of shedding more light on the many uses of theory. The concept of theoretical generations is utilized as a means of accounting for the succession of models and explanatory frameworks. PMID- 1506117 TI - The gerontological imagination: social influences on the development of gerontology, 1945-present. AB - This article presents a framework for the analysis of the development of gerontology since 1945. Three distinct historical periods and several forces that have shaped the field are examined. These forces reside in the political, economic, sociocultural, technological, and knowledge realms of society. An analysis of the continuities and discontinuities over time provides a contrast between the historical periods identified. Despite the ideology of a continuous linear disciplinary progression, we find that discontinuities have been increasingly significant in shaping the experience of aging. Yet the field of gerontology lags in reflecting many of these changes. This incongruity calls the field to reassess its paradigmatic foundations and the empirical and theoretical work conducted within them. The implications for the disciplines and practice of gerontology are explored through a review of C. Wright Mills' contribution to a revival of the "gerontological imagination." PMID- 1506118 TI - Continuity and change revisited. AB - This concluding article summarizes key points about continuity and change in gerontology as described in the four previous articles. Synthesis and discussion is focused on five major areas in which gerontological continuity and change are evidenced: 1) transformation of basic themes over time; 2) gerontology's identity crisis; 3) the social ideology of gerontology; 4) evolution and refinement of gerontological ideas and methods; and 5) temporal frameworks. The author raises questions about unsolved issues and suggests the eventual need to examine the roles of individuals in shaping the field of study called gerontology. PMID- 1506119 TI - The continuity of gerontological themes. AB - Based on the premise that scientists should periodically examine the history of their ideas and methodologies, this article focuses on the issue of continuity in the evolution of scientific knowledge about aging. Taking a twenty-five-year perspective, selected research questions and priorities in the biomedical, behavioral, and social domains of aging are used to exemplify the continuity of the gerontological knowledge base. This article concludes that there is considerable evidence of continuity, despite the strong influences of changing cohorts of people and external forces that have shaped new ideas and research questions in gerontology. PMID- 1506120 TI - Rabies antibody titers in vaccinees: protection, failure and prospects. AB - Treatment of symptomatic rabies is a challenging task as no effective drug is yet available. Hence, prophylactic immunization is an important step. The development of adequate level of antibody (greater than or equal to 0.5 IU/ml serum) is necessary for protection against the disease. In contrast to the nerve tissue vaccines, tissue culture vaccines particularly human diploid-cell strain type is highly potent and least reactogenic. To minimize the costs of immunization by this expensive vaccine, small dose intradermal administration has been advocated for developing countries with endemic rabies. Concurrent use of serum and antimalarials may interfere with adequate immune response. Efforts are in progress for the development of more potent subunit and recombinant antirabies vaccine for future human use. This review makes an attempt to study the antibody levels in the vaccinees regarding its role in the protection and failure against clinical and experimental rabies. PMID- 1506121 TI - Plasma lipid peroxides in coronary heart disease. AB - The relation between plasma lipid peroxide and coronary heart disease was investigated at Harapan Hospital in Kita Jakarta. Ninety-eight patients (83 males and 15 females), below 75 years old were included in the study. The samples consisted of 47 cases with angina and 22 cases with myocardial infarction which were proven to suffer from coronary atherosclerosis by the presence of clinical symptoms, ECG abnormalities, angiography and myocardial enzyme measurement. Controls were patients who did not show any abnormalities in the parameters used. Controls and patients were classified into several groups based on the presence or absence of risk factors (smoking, hypertension, diabetes mellitus, hyperlipidemia, obesity, family history). The results of the study showed that plasma lipid peroxide in patients with angina and myocardial infarction which were 3.26 +/- 1.07 mumol and 3.20 +/- 0.82 mumol/l, respectively, were significantly higher (p less than 0.05) than controls 2.50 +/- 0.45 mumol/l. There was no differences in total cholesterol, LDL and triglyceride contents between control and patients with coronary heart disease; whereas HDL cholesterol level was significantly higher in the patients with angina, 38.7 +/- 10.5 mg/dl vs 31.5 +/- 6.76 mg/dl in patients with myocardial infarction. Univariate analysis of various risk factors revealed a strong correlation between plasma lipid peroxide and the chance in developing coronary heart disease. The present study showed that plasma lipid peroxide was increased in coronary heart disease and that it might be used as a determinant in the assessment of the severity of the disease. An investigation on the effects of antioxidants in these patients is planned. PMID- 1506122 TI - Dermal, serological and CSF changes in amyotrophic lateral sclerosis with and without intrathecal interferon beta treatment. AB - In 12 patients with amyotrophic lateral sclerosis (ALS) participating in a therapeutic trial with intrathecally applied human fibroblast interferon-beta (IFN-beta) and in 9 untreated ALS patients, we found significantly elevated circulating serum IgG immune complexes (CIC), quantitative immunoglobulin changes, and creatine kinase (CK) elevation; CK reached significantly more often pathological levels in non-bulbar disease. Dermal ultrastructural changes were equally present in all treated as well as untreated ALS patients. Some time ago IL-6 was quantitatively cleaned out of the Fiblaferon-preparation. Erythrocyte sedimentation rate (ESR) rose during intrathecal IFN therapy in 9/10 ALS patients. In 4/4 adequately monitored motoneuron patients, this elevation coincided with a decrease of serum CK, while ESR and CK did not correlate in 60 non-ALS non-IFN neurological controls. Collagen ultrastructure, CSF total protein or barrier function, immune complexes, immunoglobulin quantitation and serum CK may contribute to differentiated diagnosis and should be included in future study protocols. PMID- 1506123 TI - Efficacy of ibuprofen in pediatric patients with fever. AB - We studied the efficacy of ibuprofen in 56 infants and children (age 0.5-12 years) with rectal temperature greater than or equal to 38.3 degrees C, using a double-blind randomized placebo-controlled design. Ibuprofen liquid was given as a single dose, 5 mg/kg to 18 patients (group I) and 10 mg/kg to 18 patients (group II); placebo was administered to 20 patients (group III). Temperature and vital signs were measured every 0.5-1.0 hours for 8 hours. Multiple blood samples were also collected over this period; ibuprofen plasma concentrations were measured by HPLC. The mean temperature was 38.3 degrees C in group I, 38.1 degrees C in group II, and 38.9 degrees C in group III during 8 hours after drug or placebo administration. The temperature was significantly lower in group I vs III (ibuprofen 5 mg/kg vs placebo) (p less than 0.0005), and group II vs III (ibuprofen 10 mg/kg vs placebo) (p less than 0.0001). The temperature was also markedly different for patients in group I vs II (ibuprofen 5 mg/kg vs ibuprofen 10 mg/kg) between 4 and 8 hours after the dose (p less than 0.01). The duration of action was longer for ibuprofen 10 mg/kg than 5 mg/kg. The mean maximum decrease from baseline temperature was 1.3 degrees C, 1.8 degrees C and 0.8 degrees C for group I, II and III, respectively. The maximum reduction in temperature occurred at 3-4 hours in the ibuprofen groups, and at 7 hours in the placebo group.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1506124 TI - Hemorrheological and circulatory effects of Gincosan. AB - Gincosan is a combined preparation containing 60 mg ginkgo biloba and 100 mg ginseng, standardized of 24% ginkgo flavone glycosides and 4% ginsenosides. Hemorrheological and circulatory effect as well as blood pressure behavior after the administration of gincosan were studied in an acute trial on 10 voluntary subjects with a mean age of 26 years. Systolic blood pressure decreased significantly both for the large-dose (120 mg ginkgo biloba +200 mg ginseng) and low-dose administration (60 mg ginkgo biloba +100 mg ginseng). Diastolic blood pressure and heart rate decreased only in the high dosage group. The pathologically increased spontaneous platelet aggregation is reduced by both dosages. Erythrocyte velocity in nail fold capillaries increased significantly only in the high dosage group. The parallel group comparison of the high dosage and placebo group showed that they differ only significantly concerning the erythrocyte rigidity, erythrocyte velocity in nail fold capillaries and spontaneous platelet aggregation. A trend towards a decrease in the systolic blood pressure is revealed (p less than 0.1). PMID- 1506125 TI - Renal effects of imidazole-2-hydroxybenzoate in patients with compensated liver cirrhosis. AB - A double-blind crossover study versus placebo of the renal effects of the nonsteroidal anti-inflammatory drug imidazole 2-hydroxybenzoate was conducted in 10 patients with compensated liver cirrhosis. The administration of the drug (750 mg, t.i.d., for three days) did not affect renal plasma flow, glomerular filtration rate, free water clearance nor the urinary excretion of sodium or potassium. Values of plasma renin activity also did not change after drug administration. Direct tubular damage from imidazole 2-hydroxybenzoate was also excluded by normal excretion of beta-2-microglobulin and N-acetyl-beta-D glucosaminidase. Urinary 6-keto-PGF1 alpha output were comparable during imidazole 2-hydroxybenzoate and placebo administration. These data indicate that this nonsteroidal antiinflammatory drug does not affect the renal function in patients with compensated liver cirrhosis. PMID- 1506126 TI - Oligohydramnios induced by maternal indomethacin therapy. AB - Indomethacin is a potent tocolytic agent used in premature labor. The most observed adverse effect was the constriction of ductus arteriosus, causing persistent fetal circulation postnatally. Until recently, decrease in amniotic fluid during treatment with indomethacin has been shown partly by subjective methods. In comparison with posttreatment results, using "amniotic fluid index", transient decrease in amniotic fluid was determined semi-quantitatively. PMID- 1506127 TI - Presentation of results from bioequivalence studies. AB - Based on general guidelines and requirements for the design and analysis of bioequivalence studies, specific recommendations are made for the presentation of results, both in tabular and graphical form. This is done by means of two examples, one of a single-dose study and one of a multiple-dose study. The recommendations in this paper are twofold. Firstly, a complete and rather detailed presentation of results is given, which practically corresponds to the standard of research reports. Secondly, a subset of this is suggested for publication. It gives the essential results for bioequivalence assessment in a standardized form. From an editorial point of view, it would be highly appreciated if the papers submitted for publication were always accompanied by a complete presentation including the individual concentration/time data and the various steps of calculation. This would speed up peer review and ultimately improve and harmonize the standard of bioequivalence publications. PMID- 1506128 TI - The effect of nerve blockade on forearm and finger skin blood flow during body heating and cooling. AB - To determine the role of the active cutaneous vasodilatator response in forearm and finger skin, direct assessment of only skin blood flow was performed before and after musculocutaneous and median nerve blockade during whole body heating and cooling. Forearm laser Doppler flow (LDF forearm), forearm heat thermal clearance (HTC forearm), and finger laser Doppler flow (LDF finger) were monitored in the nerve blocked skin and contralateral untreated skin (control). In the pre-blockade period, no significant differences were found between experimental and control arm skin. After nerve block a significant increase occurred only in LDF finger, which rose from 4.3 +/- 0.6 to 6.0 +/- 0.5 volts (p less than 0.05). During whole body heating LDF forearm and HTC forearm increased significantly on both arms. The increase in LDF forearm was greater (p less than 0.05) in control (18.3 +/- 1.2 volts) than in nerve blocked skin (14.6 +/- 1.8 volts) and occurred earlier. The same tendency was observed in HTC forearm between nerve blocked skin (0.522 +/- 0.06 W.m-1.degrees C-1) and control 0.671 +/- 0.037 W.m-1.degrees C-1) (NS). LDF raise up to 6.6 +/- 0.5 and 6.8 +/- 0.5 volts in the blocked finger and in the control respectively. During cooling LDF finger in the control decreased to 1.3 +/- 0.1 volt and was significantly (p less than 0.05) lower than in the resting period, and lower than that in the nerve blocked finger (3.4 +/- 0.8 volts) (p less than 0.05). We conclude that the active vasodilatator system plays an important role as far as the timing and the amplitude of the cutaneous vasodilatator response to whole body heating in the forearm but not in the finger. At thermal neutrality, the vascular vasoconstrictor tone is high to the finger but not to the forearm. The vasoconstrictor response to cooling occurred only in the finger. PMID- 1506130 TI - Spontaneous oscillations of laser Doppler skin blood flux in peripheral arterial occlusive disease. AB - In the present study, local temporal fluctuations of skin perfusion were non invasively measured at the forefoot and calf in 374 limbs of 226 patients with peripheral arterial occlusive disease (PAOD) by means of Laser-Doppler-Flowmetry (LDF). Within the scope of a purely descriptive evaluation, each recording was classified according to four previously defined LDF oscillation types named 'aperiodical', 'sinoidal', 'missing waves', and 'small waves'. The prevalences of these curve patterns distinctly varied with both the macrohemodynamic compensation and clinical severity of PAOD. While type 'aperiodical' predominated in case of a normal or only slightly affected circulation, type 'sinoidal' accumulated in legs with marginal collateralization. In contrast, 'missing waves' and 'small waves' mainly occurred in feet affected by severe PAOD. Which pathophysiological mechanisms are responsible for the different LDF oscillation types still remains to be clarified. Retrospectively, in case of a confirmed PAOD, the diagnosis of critical limb ischemia could not be established and wound healing could not be predicted by means of LDF pattern analysis. PMID- 1506129 TI - Microangiopathy in Ehlers-Danlos syndrome type IV. AB - In two patients with Ehlers-Danlos syndrome type IV, an autosomal dominant disorder characterized by fragility of large vessels, excessive bruising, and deficiency in type III collagen, capillary microscopy was performed at the nailfold. Indocyanine green and Na-fluorescein were used as fluorescent tracers. Both patients exhibited microangiopathy of the skin capillaries with microbleedings, presence of microaneurysms and increased transcapillary diffusion. Microvascular involvement appears to be an additional manifestation of the syndrome. PMID- 1506131 TI - Alteration of microvascular responses to serotonin in the diabetic rat. AB - This study examined the microvascular response to serotonin (5-hydroxytryptamine; 5-HT) in short-term streptozotocin-induced diabetic rats. 5-HT was applied topically to the neurovascularly intact and environmentally controlled cremaster muscle of the two-week diabetic rat. Intravital microscopy was used to measure the diameters of large arterioles (First-order; A1) and small arterioles (Third order; A3), and the FITC-albumin leakage in small venules (Third-order; V3). The diabetic animals were divided into two groups based on the dilator capacity of the A3 arterioles: the Diabetic-Tone group had a dilator capacity of 98 +/- 14.5% compared to 11 +/- 4.1% for the Diabetic No-Tone animals. 5-HT caused significantly greater constriction of A1 arterioles in Diabetic-Tone animals (-40 +/- 6%) than in either the Control (-19 +/- 6%) or Diabetic No-Tone (-18 +/- 5%) animals. 5-HT dilated the A3 arterioles to a similar degree in both the Diabetic Tone and Control groups, but the Diabetic No-Tone group did not dilate to 5-HT because the A3 arterioles in these animals possessed no basal tone. Control animals showed a large 5-HT concentration-dependent increase in leakage of albumin in V3 venules, but this response was inhibited in the Diabetic-Tone animals. The 5-HT-induced leakiness in the Diabetic No-Tone group was intermediate between the other two groups. These results show that large arteriole constriction and small venule permeability responses to 5-HT are altered early in the development of diabetes, and are different in those animals with and without basal arteriolar tone. These data suggest that streptozotocin induced diabetes alters microvascular function in striated muscle by at least two different cellular mechanisms. PMID- 1506132 TI - Attenuation of hypoxic response in cerebral microcirculation following deprenyl. AB - Cerebral blood flow (CBF), cerebrocortical microflow (CMF) and local pO2 were measured in the rat brain cortex during normoxia and hypoxic hypoxia before and after administration of the monoamine oxidase-B (MAO-B) inhibitor deprenyl (0.1 mg/100 g b.wt. i.v.). CBF was measured using intraarterial 133-Xenon injection technique. Both, CMF and pO2 were measured using polarographic multiwire surface electrodes. In the control group without deprenyl CBF increased during hypoxaemia (PaO2 = 44.7 +/- 9.3 mm Hg) by 215% while CVR decreased to 27% of the normoxic control value. Hypoxaemia (PaO2 = 34.4 +/- 3.9 mm Hg) also led to a mean increase of CMF by 38% of the normoxic control (p less than 0.02) while the local cerebrocortical pO2 fell from 20.1 +/- 5.1 mm Hg to 5.2 +/- 1.9 mm Hg (p less than 0.02). The administration of deprenyl during normoxia did not cause any significant changes of CBF and CMF although both increased by 29% and 28%, respectively. The increase of CBF during hypoxaemia (PaO2 = 34.9 +/- 6.3 mm Hg) following deprenyl administration, although diminished, was still present (101%, p less than 0.01). CMF decreased under these conditions by 30% on average (p less than 0.05). These results suggest that MAO-B may be involved in the local regulation of cerebrocortical capillary blood flow during hypoxia. PMID- 1506133 TI - Age and site variability of skin blood perfusion in the hairless mouse ear determined by laser Doppler flowmetry. AB - Laser Doppler Flowmetry (LDF) was used to characterize skin blood perfusion variations present within the Homozygous Hairless mouse ear microvasculature as a function of 1) arteriolar level within the microvasculature, 2) animal age and 3) LDF probe distance above the tissue being studied. To this end blood perfusion measurements (arbitrary perfusion units) were made in the ear at vascular sites in the vicinity of primary vessels (site A), secondary vessels (site B), tertiary vessels (site C), and peripheral zones distant from larger vessels. These were done without any invasive procedures save anesthesia administration and were carried out at three different tissue-probe distances (0.5, 0.75 and 1.0 mm) on three groups of eight mice each with ages of three, five and eight weeks. Results show a significant gradient in perfusion from sites A to D in each age group and a significant increase in perfusion with increasing age. The effect of probe tissue distance variations on perfusion values was found to be significant between 0.5 mm and 1.0 mm but overall differences were small. In addition to these specific findings the present results demonstrate the potential of LDF as a means of detecting, evaluating and correlating perfusion changes, either by itself or as a complementary method to detailed microvascular measurements using conventional in vivo microscopy. PMID- 1506134 TI - Renal microvascular perfusion evaluated by single fibre laser Doppler flowmetry. AB - The single fibre laser Doppler flowmetry technique has been designed to perform continuous quantification of microvascular perfusion deep in tissue. In this study we have evaluated the use of the technique in renal tissue. A total number of 164 recordings were analyzed. Fluctuations in perfusion related to heart rate and respiration were observed. The possible nature of the low-frequency flow motion waves (10-12 min-1) is discussed. No significant difference in perfusion level could be detected between the upper, the middle and the lower parts of the kidneys (p greater than 0.69), or between the cortex and the medulla (p = 0.77). The spatial variation, expressed as the difference between two consecutive measurements, was large. The median and mean values of groups of data are however reproducible. When the renal artery is reopened after 30 sec of occlusion, the pre-occlusive flux levels are regained after approximately 1.5 sec. The single fibre laser Doppler flowmetry technique can be used for renal microcirculatory studies, but comparative studies with other methods have to be performed. PMID- 1506136 TI - Attitudes towards mental patients. AB - A study of attitudes towards mental patients was made using a questionnaire developed by Lehtinen and Vaisanen. Five hundred and fourteen persons from different parts of Finland filled in the questionnaire. The attitudes were generally positive, although, as in other studies, the attitudes of those older and less educated were more negative compared with the other groups. This result was interpreted as a generational effect, which will vanish as the educational level of the population increases. The questionnaire also included questions about the attitudes and behaviour of 'other people'. The attitudes of 'other people' were thought to be very negative compared with one's own attitudes. PMID- 1506135 TI - Supportive housing: a consumer evaluation study. AB - The current debate about how to provide housing for persons with persistent psychiatric disabilities should be informed by empirical information from a variety of sources. Data from a study of 17 residents discharged from Regeneration House Inc., illustrates the value of consumer perceptions in the evaluation of supportive housing. Extensive exploration of the positive and negative aspects of living in a group home from the perspective of experienced residents provides useful input for programme planning. The implications of the findings for the individual programme and the wider field are discussed. PMID- 1506137 TI - 'Not waving but drowning': psychiatric inpatient services in East Lambeth 1990. AB - This paper presents the results of the latest in a series of surveys of an inner city public psychiatric inpatient service. Severe pressures on the service had led to the purchase of inpatient beds in the private hospital sector and intensive care facilities in a large psychiatric hospital. On a census day the nominal occupancy for the inpatient unit was 117%. Implications of the survey, trends over time and possible solutions to the difficulties of the inpatient unit are discussed. PMID- 1506138 TI - Pretreatment expectations of New Zealand clients receiving cognitive-behavioural psychotherapy: comparison with a North American sample. AB - A study of New Zealand clients' expectations of psychotherapy was conducted using the Psychotherapy Questionnaire (PQ). The PQ was administered to 141 New Zealand clients attending their first appointment with a clinical psychologist. The New Zealand clients' expectations were compared to previous research using a sample of USA clients who also completed the PQ prior to their first visit with a therapist. Those differences between the NZ and USA samples were consistent with previous research comparing the expectations of non-American samples. In general the NZ sample expected to be more passive in therapy than the USA sample and did not expect to have to discuss difficult or uncomfortable topics. Despite these differences there were suggestions that NZ and USA clients may have more similarities than differences with regard to their expectations about psychotherapy. PMID- 1506139 TI - Lay explanations of symptoms of mental ill health in Kuwait. AB - The cognitive schemas of 208 subjects were elicited in relation to 12 hypothetical symptoms which are most commonly presented by patients suffering from psychiatric disorder. Three types of explaining schemas were recognised as physical, psychosocial and supernatural explanations. Somatic symptoms tended to have physical explanations and emotional symptoms tended to have psychosocial explanations although both are known in clinical practice to indicate psychiatric disorder and to disappear together when the disorder recovers. Supernatural explanations were most likely in elderly males and in extended families. Symptoms associated with supernatural cognitive schemas fit in with the cultural background and not with the level of modern education achieved. PMID- 1506140 TI - Joshua Bierer and social psychiatry. PMID- 1506141 TI - Bierer's precepts today and tomorrow. The Fifth Joshua Bierer Memorial Lecture delivered to the British Association for Social Psychiatry, 23 May 1991. PMID- 1506142 TI - Community-based treatment of psychiatric disorders in U.S.A. and Norway: insights for new service delivery systems. AB - This article reports on a successful community-based psychiatric treatment program in Philadelphia, Pennsylvania and describes subsequent experiences seeking approval of similar programs in Philadelphia and in Oslo, Norway. Previous studies have shown that the Philadelphia community-based program, which used patient social networks and indigenous community workers assisted by psychological and psychiatric professionals, provided better treatment outcomes than traditional hospital programs and socioenvironmental treatment programs. On the basis of these experiences a new service delivery system was proposed which integrates patient social networks, community workers, and lay community organizations with mental health center professionals. Examination of differences in official responses to the proposal shows the importance of several factors, including the mental health bureaucracy's perception of patient potential, their openness to social psychological therapy, and the power struggles within the bureaucracy and the professional community. PMID- 1506143 TI - Functional components of microtubule-organizing centers. PMID- 1506144 TI - The specialized junctions of the lens. PMID- 1506145 TI - Colloidal gold and its application in cell biology. PMID- 1506146 TI - Molecular and cellular basis of formation, hardening, and breakdown of the egg envelope in fish. PMID- 1506147 TI - Pharmacokinetic behavior of gadoteridol injection. AB - RATIONALE AND OBJECTIVES: To assess the safety and pharmacokinetics of gadoteridol injection (0.5 M) in 18 healthy male volunteers in a phase I clinical trial. METHODS: Volunteers were assigned to one of six dosing groups: 0.05, 0.1, 0.15, 0.2, 0.25, and 0.3 mmol/kg gadoteridol (0.5 M), in an ascending dose study. Physical examination, vital signs, electrocardiogram, clinical laboratory tests, and serum and urine samples were obtained at selected time points before and after administration of gadoteridol. RESULTS AND CONCLUSIONS: No significant changes in vital signs, physical examination, clinical laboratory values, or electrocardiogram, that were believed by the principal investigator to be related to the administration of the contrast agent, were observed. A single adverse event (transient hive) believed to be related to contrast agent administration was observed in one volunteer. Pharmacokinetic data show that the elimination half-life and the distribution half-life were independent of the dose used. The mean distribution half-life was 0.20 +/- 0.04 hours, the mean elimination half life was 1.57 +/- 0.08 hours, and greater than 94% of the drug was excreted in the urine in 24 hours. PMID- 1506148 TI - Phase II clinical trial of gadoteridol injection, a low-osmolal magnetic resonance imaging contrast agent. AB - RATIONALE AND OBJECTIVES: The safety and efficacy of a new, low-osmolal magnetic resonance imaging contrast medium, gadoteridol injection, were evaluated in a phase II, open-label study at doses ranging from 0.05 to 0.30 mmol/kg. METHODS: Eighty-six patients with a diagnosis of intracranial tumor received gadoteridol injection followed by magnetic resonance imaging. RESULTS: Two adverse events (headache, taste disturbance) in 2 of 86 (2.3%) patients were reported. Both were of mild intensity and resolved without treatment and without residual effects. In 4 of 86 (4.7%) patients, 5 laboratory changes were reported by the investigators as possibly related to gadoteridol injection. Efficacy evaluation was conducted in 80 of the 86 patients who received gadoteridol injection. In these patients, a total of 119 lesions was identified, and each was evaluated at four time points after contrast administration, yielding a total of 476 lesion studies. Marked enhancement was demonstrated in 402 of 476 (84%) lesions, whereas slight enhancement was demonstrated in 62 of 476 (13%) lesions. The difference in both the incidence and degree of enhancement of pathology between the predose and postdose images was highly significant (P less than .001). CONCLUSIONS: Overall, enhanced images provided more diagnostic information and facilitated detection of more lesions than precontrast images. Gadoteridol injection at doses up to 0.3 mmol/kg is a safe and effective magnetic resonance imaging contrast agent for use in patients with intracranial tumors. PMID- 1506149 TI - Physicochemical properties of gadoteridol and other magnetic resonance contrast agents. PMID- 1506150 TI - Efficacy of gadoteridol for magnetic resonance imaging of the brain and spine. AB - RATIONALE AND OBJECTIVES: The efficacy of gadoteridol for contrast enhancement of central nervous system pathology was assessed in a multicenter clinical trial involving 411 patients suspected of having intracranial or spinal pathology. METHODS: Magnetic resonance imaging was performed before and after intravenous administration of 0.10 mmol/kg gadoteridol. Two groups of images were interpreted by one of two neuroradiologists blinded to patient history. The results were analyzed separately. RESULTS: Patients with radiologic evidence of disease demonstrated enhancement of intracranial pathologic lesions in 44 of 63 (70%) and in 91 of 111 (82%) cases, respectively, whereas enhancement of spinal lesions was observed in 36 of 58 (62%) and in 65 of 78 (83%) cases, respectively. Subjectively, postcontrast scans provided more information than precontrast images in 37 of 63 (59%) and 84 of 111 (76%) intracranial cases, respectively, and in 25 of 58 (43%) and 55 of 78 (71%) spinal cases, respectively. Additional information included the subjective sense that there was improved visualization of pathology and definition of lesion borders. CONCLUSIONS: Subjective assessment of magnetic resonance scans suggest gadoteridol is an effective intravenous contrast agent for magnetic resonance imaging. PMID- 1506151 TI - Phase III clinical studies with gadoteridol for the evaluation of neurologic pathology. A European perspective. AB - OBJECTIVES AND RATIONALE: The use of paramagnetic contrast agents has improved the diagnostic sensitivity and specificity of magnetic resonance imaging (MRI) for evaluating diseases of the central nervous system. To assess the safety and imaging properties of the nonionic, gadolinium-based MRI contrast agent gadoteridol, 151 patients and controls were evaluated for safety, and 118 patients with cerebral or spinal pathology were evaluated for imaging efficacy. METHODS: Precontrast T1- and T2-weighted spin-echo images and postcontrast (0.10 mmol/kg) T1-weighted spin-echo images were read by unblinded investigators at each site. RESULTS: The rate of adverse events possibly or probably related to gadoteridol was 4.0% (vasodilation [facial flushing], 1 patient; nausea, 3 patients; urticaria, 2 patients). Laboratory changes were reported in 6.0%. None of these events or changes was considered to be clinically significant. Contrast enhancement was noted in 75% of cases with brain pathology and 64% of cases involving spine lesions. CONCLUSIONS: Gadoteridol is safe in routine clinical use at a dose of 0.10 mmol/kg and provides improved lesion detection compared to plain MRI. PMID- 1506152 TI - Review of the use of high-dose gadoteridol in the magnetic resonance evaluation of central nervous system tumors. PMID- 1506153 TI - Efficacy of gadoteridol for contrast-enhanced magnetic resonance imaging in children. AB - RATIONALE AND OBJECTIVES: This study assesses the efficacy of gadoteridol for contrast-enhanced magnetic resonance imaging (MRI) in children. METHODS: Patients were examined by MRI before and after receiving 0.10 mmol/kg gadoteridol. Blinded and unblinded readers analyzed brain and spine MRI studies from a multicenter clinical trial involving 101 patients at 11 sites. Ninety-two cases (76 brain, 16 spine) were evaluated by unblinded investigators, and 91 cases (76 brain, 15 spine) were evaluated by three neuroradiologists unaffiliated with any investigational site and blinded to clinical information. RESULTS: Unblinded readers noted enhancement of brain pathology in 70% of cases versus 50% to 67% among blinded readers. Unblinded readers determined that additional diagnostic information was available after contrast in 82% of brain studies (average, 64% for blinded readers) and would have changed patient diagnoses in 48% of these studies (average, 46% for blinded readers). In spine cases, enhancement of pathology was noted in 38% (unblinded) and 33% to 40% (blinded). Additional diagnostic information was available after contrast in 63% of spine studies (unblinded), or an average of 58% (blinded), and patient diagnoses would have changed in 20% (unblinded), or an average of 59% (blinded). CONCLUSIONS: Gadoteridol is suitable for enhanced MRI detection, localization, and characterization of central nervous system pathology in children. PMID- 1506154 TI - Efficacy of gadoteridol for magnetic resonance imaging of extracranial head and neck pathology. AB - RATIONALE AND OBJECTIVES: This study evaluated the efficacy of gadoteridol in patients with extracranial head and neck pathology. METHODS: One hundred twenty two magnetic resonance imaging (MRI) cases from a multicenter safety and efficacy trial of gadoteridol in patients with suspected head and neck pathology were randomly assigned for evaluation to one of two blinded neuroradiologists. RESULTS: Enhancement of pathology after gadoteridol injection was noted in 96 cases (78.7%) and provided additional diagnostic information in 57 cases (46.7%). Improved lesion visualization was noted in 37 (64.9%) of these 57 cases; an increase in the number of lesions seen was noted in 4 (7.0%) of 57 cases. Blinded readers determined that additional diagnostic information provided by gadoteridol would have resulted in a change in diagnosis in 20 (35.1%, or 16.4% of total population) of 57 patients. CONCLUSION: These results demonstrate that gadoteridol is an efficacious agent for enhanced MRI of head and neck pathology. PMID- 1506155 TI - Future applications of contrast agents for magnetic resonance imaging of the central nervous system. PMID- 1506156 TI - Future applications of magnetic resonance contrast agents in the abdomen. PMID- 1506157 TI - Summary of preclinical safety evaluation of gadoteridol injection. AB - RATIONALE AND OBJECTIVES: To support clinical use of gadoteridol (0.5 M) injection, a battery of in vitro and in vivo safety studies was conducted. RESULTS: In mice, the acute intravenous LD50 for gadoteridol (0.5 M) injection was 11 to 14 mmol/kg, and the intravenous minimal lethal dose in rats was greater than 10 mmol/kg. In 2-week studies with gadoteridol, no serious effects were observed in mice given 3 mmol/kg or dogs given 1.5 mmol/kg daily. In a series of reproduction studies, no treatment-related adverse effects on fertility, reproductive performance, or postnatal development were seen in rats at doses of 1.5 mmol/kg or less, and no teratogenic effects were observed at doses as high as 6 mmol/kg in rabbits and 10 mmol/kg in rats. In an in vitro test, gadoteridol did not demonstrate any potential to hemolyze human erythrocytes when incubated in high concentrations with whole blood, suggesting there is little probability gadoteridol will cause hemolysis in vivo. CONCLUSIONS: A substantial margin of safety exists for the clinical use of gadoteridol in magnetic resonance imaging procedures. PMID- 1506158 TI - Alveolar soft part sarcoma presenting as a pulsating tumour of the arm in a young woman. PMID- 1506159 TI - Endometrial and pulmonary sarcoidosis. AB - A 33 year old woman with irregular menses due to endometrial sarcoidosis and a family history of sarcoidosis is described. Its relative increase in importance in the wake of the decline in the incidence of genital tract tuberculosis in Ireland is discussed. PMID- 1506160 TI - Congenital diaphragmatic hernia in the newborn. Outcome in 59 consecutive cases over a ten year period (1980-1989). AB - A ten year review (1980-1989) of 59 neonates presenting with congenital diaphragmatic hernia (CDH) to Our Lady's Hospital for Sick Children, the main referral centre for neonatal surgery in Ireland, is presented to determine the outcome and make suggestions for improvements. CDH was more common in males (34M, 25F). The hernia was present on the left side in 47 cases and 11 cases were right sided. Overall mortality was 35.6%, with increased mortality for right-sided hernia (54.5%). Mean gestation period for survivors was 39 weeks and for non survivors was 36 weeks. Fifty-two (88.1%) patients presented with symptoms within first six hours after birth. Nineteen of 59 patients (32%) did not have their airways secured with an endotracheal tube at the time of arrival in the hospital. Recurrent chest infections and gastro-oesophageal reflux were the most common long term complications. The prognosis was better for late presenters. A period of prolonged ventilatory stabilisation with appropriate inotropic support to help correct acidosis before surgery improved results. Surgery should be postponed until ventilatory stabilisation is established. A protocol for safe transport of patients to the referral centre is recommended. It is advisable that all patients with congenital diaphragmatic hernia be intubated as soon as the diagnosis is made and that a doctor accustomed to airway management accompanies the patient to the neonatal surgical centre. PMID- 1506161 TI - Blood cultures and antibiotic use in a neonatal intensive care unit. AB - A review of the duration of antibiotic courses in our Neonatal Intensive Care Unit (N.I.C.U.) has shown that in a significant number of cases there was non compliance with the antibiotic policy. An audit of neonatal sepsis and antibiotic usage over a six month period was performed in the N.I.C.U. at the Rotunda Hospital. Three hundred and forty-nine of the 3,163 infants born during this time were admitted to the N.I.C.U. One hundred and fifty-two infants had one or more episodes of suspected sepsis. In 168 instances this preceded a course of antibiotic therapy lasting longer than 48 hours. In 56 (33%) the infant was clinically septic and in 16 (9.5%) of those there was bacteriological proven sepsis. There were 112 episodes (60%) where there was no strong clinical evidence of sepsis and a negative investigation for sepsis where antibiotics were continued for more than 48 hours. The possible reasons why antibiotics were not stopped include the non specific nature of signs of sepsis in neonates, physicians' reluctance to discontinue antibiotics once started, and the logistic difficulty of obtaining routine culture results at weekends. The study emphasizes the need for regular surveillance of antibiotic usage in a N.I.C.U. PMID- 1506162 TI - Interlocking intramedullary nailing for the treatment of tibial fractures. AB - Thirty-seven tibial shaft fractures in 34 patients were treated with the Grosse Kempf interlocking intramedullary nail over a two year period. Thirty-six tibiae were consolidated at a median of 17 weeks; one had re-fractured following nail removal in a separate injury, but was now uniting on conservative treatment. Using very detailed clinical and radiological analysis, and excluding the patient who had re-fractured, the results were excellent in 19, good in 8, fair in 6 and poor in 3. The most significant complications were haematoma formation and additional comminution during nail insertion. Overall, we found tibial nailing to be a satisfactory procedure, facilitating rapid rehabilitation with early weight bearing and resulting in predictable fracture healing in good alignment. PMID- 1506163 TI - Worksite screening for high blood cholesterol: implications for detection, evaluation and treatment--the Israel CORDIS Study. AB - Current recommendations for optimal blood cholesterol levels could have major implications for the detection, evaluation and treatment of high blood cholesterol in Israel. During 1985-87, in the framework of the CORDIS Study, a sample of 3,556 males and 1,558 females, aged 20-64, employed in Israeli industry were screened at the worksite for lipids, lipoproteins and other cardiovascular risk factors. From the age-group 20-24 to 60-64 years, the prevalence of high blood cholesterol (greater than 239 mg/dl) increased from 1.6% to 34.3% for males and from 5.4% to 36.7% for females. Ethnic differences were present, with those from Western countries generally having the highest prevalence. When examined in two age-groups, 20-44 and 45-64 years respectively, 28.6% and 54% of males and 8.8% and 37.5% of females had a combination of cholesterol levels and coronary heart disease (CHD) risk factors for which lipoprotein analysis is currently recommended. There was an increase in the prevalence of high blood cholesterol with increased number of non-lipid CHD risk factors (for 0 to greater than or equal to 3 risk factors, age-adjusted prevalence ranged from 18.2 to 37.5% for males and 9.6% to 41.4% for females). Less than 5% of those with high blood cholesterol were aware of their condition, and less than 1% were under treatment. The prevalence of high blood cholesterol in the working population is Israel appears to be similar to that of the United States. Age-related changes in low density and high density lipoprotein cholesterol levels are such that monitoring of cholesterol in most people need not be more frequent than every 3-5 years. Any cholesterol screening program should be designed to allow for varying schedules according to age, sex and the presence of other risk factors for cardiovascular disease. PMID- 1506164 TI - Is eye cosmetic a source of lead poisoning? AB - Kohl is a lead-containing eye cosmetic applied to many infants in Israel and in other countries in the Middle East. Seven samples of kohl used in our region contained 17.3%-79.5% lead. We assessed 24 kohl users and 30 non-kohl users, aged 6-16 months, for blood lead, zinc protoporphyrin, hemoglobin, mean corpuscular volume (MCV), serum iron and calcium. Blood lead levels were significantly higher in the infants to whom kohl was applied (11.2 vs. 4.3 micrograms/dl, P less than 0.001) and were greater than 20 micrograms/dl in three of them. In the non-kohl users, blood lead levels were significantly higher in infants whose mothers used kohl (5.2 vs. 2.8 micrograms/dl, P less than 0.02). No significant differences were found in the other parameters. The kohl-using infants were significantly shorter at 3-5 weeks of age (P less than 0.005) but not at the time of the study. No significant differences were found in weight and head circumference at birth or at the time of the study between kohl-using infants and controls. Regression analysis showed that among the analyzed variables the infant's blood lead level was related only to the use of kohl. We conclude that application of kohl to the infant's or mother's eyes is associated with a significant increase in the infant's blood lead levels and in the minority of cases with asymptomatic lead poisoning. PMID- 1506166 TI - Plasma dopamine beta-hydroxylase activity in familial Mediterranean fever. PMID- 1506165 TI - A multidimensional autoantibody analysis specifying systemic lupus erythematosus patients with neuropsychiatric symptomatology. AB - Utilizing a newly perfected multiple-response permutation procedure, we analyzed the autoantibody titer of systemic lupus erythematosus (SLE) patients during active and convalescent periods of disease, SLE patients without neurological involvement, and three other comparison groups (patients with active tuberculosis, patients with multiple sclerosis, and healthy normal controls). The multidimensional analysis we used distinguished those SLE patients with neurological involvement from the other SLE patients. Differences were noted by a univariate analysis measuring antibodies to single- and double-stranded DNA, poly (G), Sm, RNP, Ro, La, and gangliosides. Elevated concentrations of the common anti-DNA idiotype 16/6 were also noted among SLE patients with neuropsychiatric illness. This report stresses that increased disease activity in SLE patients with neuropsychiatric phenomena is reflected by their autoantibody profile. PMID- 1506167 TI - Premature mortality, Israel 1986. AB - Mortality statistics serve as the most common tool for health policy planning. However, this method suffers from several shortcomings. The mortality patterns in Israel in 1986 are presented in this article using the measure of years of potential life lost (YPLL), which better expresses premature mortality and the burden of diseases on society. Ischemic heart disease, cancer, and accidents of all types are responsible equally for most premature deaths in males in Israel, whereas cancer is the leading cause of premature mortality in women in Israel. Planning future health policy should rely more heavily on measures such as YPLL. PMID- 1506168 TI - Falls among elderly people living at home: medical and social factors in a national sample. AB - Falls are the most common accidents among the elderly, and while medical risk factors are well known, less is known about the association of falls with social factors. The aims of this study were to estimate the incidence rate of falls in a national, representative sample of Israeli elderly and to examine the association of falls with selected medical and social factors. A special national survey conducted in 1985 by the Israel Central Bureau of Statistics showed that among a representative sample of 3,494 community-dwelling elderly persons aged greater than or equal to 65, 24% reported a fall in the past year; the rate was 16% among men and 31% among women. The majority of falls reported happened out of doors. Of those who fell 37% subsequently visited the emergency room. Analyses adjusted for age and sex showed that single persons, particularly women, living alone reported falls at a higher rate than their married counterparts. Analyses adjusted for age, sex and mobility level showed that frequency of social interaction was inversely related to reported falls. Use of sleeping pills, problems with vision, and mobility restrictions were associated with falls in age- and sex-adjusted analyses. Advanced age (greater than 75 years) was associated with repeated falls that occurred both in the home and outdoors. PMID- 1506169 TI - 'Acceptable' lead exposures in Israel: do they lower childhood IQ and damage workers' health? PMID- 1506170 TI - Neuropsychiatric involvement in systemic lupus erythematosus. PMID- 1506171 TI - Falls in the elderly: a new challenge in medicine. PMID- 1506172 TI - Quotation accuracy: fact or fiction? AB - Results from original studies are not always correctly represented in subsequent medical publications. In this study, randomly selected quotations from Israeli medical journals were examined. Less than 80% of the examined statements were in complete agreement with the original source. In about 7% the cited reference failed to substantiate the previous author's statement. Similar results were found over a range of American and European general and speciality journals. It is concluded that errors in quotation are a widespread problem in the biomedical literature. Editors and peer reviewers can improve quotation accuracy by stressing this issue in decisions regarding publication. Nevertheless, it seems that the most efficient solution would be for authors to increase their vigilance in accurately quoting results and statements from previous publications. PMID- 1506173 TI - 21st annual meeting of the Israel Immunological Society. Rehovot, Israel, 30 April-1 May 1991. Abstracts. PMID- 1506174 TI - Not all that glitters is gold. PMID- 1506175 TI - Genetic secrets: social issues of medical screening in a genetic age. PMID- 1506176 TI - First fruits: genetic screening. PMID- 1506177 TI - Genetic diagnosis of human embryos. PMID- 1506178 TI - Playing with propranolol. PMID- 1506179 TI - The nurse as patient advocate. PMID- 1506180 TI - The transplant baby from outer space. PMID- 1506181 TI - Where ethics comes from and what to do about it. PMID- 1506183 TI - Second thoughts on "second thoughts". PMID- 1506182 TI - Second thoughts on "second thoughts". PMID- 1506184 TI - Second thoughts on "second thoughts". PMID- 1506185 TI - Second thoughts on "second thoughts". PMID- 1506186 TI - Second thoughts on "second thoughts". PMID- 1506187 TI - Taking families seriously. PMID- 1506188 TI - From the Chief Medical Officer. PMID- 1506189 TI - The delivery of interim discharge summaries to general practitioners by the elderly. AB - Two hundred and four patients discharged from an acute geriatric unit were given an interim discharge summary for delivery to their General Practitioner (GP). All but three summaries were received by the practices. Information regarding mode and timing of receipt was available in 191 patients. The summaries were received in a median of 1.0 day in both those living alone and those living with family; 75% of summaries had been received within two days of discharge and 93% within four days. General practitioners collected the summaries from patients' homes in a high proportion of both groups. Interim discharge summaries should be given to elderly patients for delivery to their GPs: this is both reliable and rapid, and clearly more cost-effective than any other form of delivery. PMID- 1506190 TI - Bed blocking in Edinburgh hospitals. AB - A point prevalence survey of in-patients in all acute hospitals within the city of Edinburgh in 1988 identified 224 elderly patients (65 and over) waiting for long stay care. This represents a 'bed blocking' rate of 19% across all specialties. The highest rate was found in Orthopaedic second line beds (approximately 33%) followed by Geriatric Assessment beds (approximately 30%); Acute General Medical Beds had approximately 13% of their beds blocked. Some 75% of the 224 patients were waiting for Geriatric long stay beds, 5% for Psychogeriatric, and a substantial proportion waiting for continuing care outwit the NHS (nearly 9% for Private Nursing Homes and 11% for residential accommodation). A repeat of this survey in 1990 revealed a small overall drop in bed blocking rate (18%) with moderate changes within the specialty groupings. However a substantial increase (from 20% to 32%) had occurred in those awaiting non-NHS accommodation, and a drop in those waiting for Geriatric Care (75% to 62%). PMID- 1506191 TI - A survey of psychiatric intensive care units in Scotland. PMID- 1506192 TI - Telephone calls to a paediatric accident and emergency department. AB - We report a survey of telephone calls to an Accident and Emergency Department. Telephone calls form a significant part of the workload of an Accident and Emergency Department. The differences between telephone advice from an Accident and Emergency Department and general practice are highlighted. In general telephone advice from the Department is a useful adjunct to the service provided by the NHS. The possibility of medico-legal implications is discussed. PMID- 1506193 TI - Child sexual abuse in general practice in north east Scotland. AB - All Grampian and North Tayside General Practitioners (GPs) were surveyed by a postal questionnaire to find out how often they had seen victims of child sexual abuse in the last two years; how they managed these patients; and whether any measures were needed to improve interagency working, especially at Case Conferences. A total of 73% of GPs replied, and 73% of these had seen at least one victim of child sexual abuse in the last two years. From this survey GPs saw approximately 2.5 victims per 1,000 per year for girls aged under 16 years. GPs' experience, views and practice varied considerably, even in one geographical area, and 72% of them felt they needed more information on child sexual abuse. PMID- 1506194 TI - Scottish gynaecologists: their views on hormone replacement therapy. AB - In a postal questionnaire Scottish gynaecologists were asked their views on the use of Hormone Replacement Therapy (HRT). They were almost unanimous in support of HRT, but varied in the circumstances in which they would recommend it and in the length of time they would prescribe it. The need for designated Menopause Clinics was seen to be limited, with most smaller Units preferring the present practice of menopausal patients being seen at general Gynaecology Clinics. Most of those replying thought that General Practitioners (GPs) should continue to be the main providers of the therapy but 89 (77%) felt that Well Women/Family Planning Clinic (WW/FPC) doctors could be an alternative source. Several problems associated with the use of the therapy were indicated. These included uncertainties about the risks of long term use and the management of unscheduled vaginal bleeding, but there was also concern over the administrative and prescribing costs if the therapy is to be widely used as prophylactic medication. PMID- 1506195 TI - The ergonomic analysis of a trauma resuscitation room. AB - Ergonomics is the practical and scientific study of people in relation to their working environment. We describe its application to the operation of a trauma resuscitation room. We used specifically designed computer software. This methodology enables a unique and objective assessment of the design and operation of a clinical system. It may be particularly applicable to other hospital areas where the efficient interaction of staff, patients and equipment is crucial to the optimal clinical outcome. PMID- 1506196 TI - The roles of general and geriatric medicine in the provision of acute medical care for elderly patients. AB - To determine whether there are differences between elderly patients admitted acutely to general medicine and those admitted to geriatric medical wards, and whether the patients are appropriately referred, a prospective survey of 426 consecutive patients aged 65 years or over admitted acutely to general medical and geriatric wards over a three month period was performed. A total of 286 patients were admitted to general medicine (GM) and 140 to the geriatric unit (GER). GER patients were older (81.0 v. 75.8 years) and had greater pre-morbid functional impairment and incontinence. Fewer GER patients presented with readily apparent organ specific diagnoses (56% v. 94%). Median length of stay was longer in GER patients (23 days v. 9 days). Variables independently predictive of GER admission were increasing age, increasing duration of illness, poor pre-morbid functional status and prior reliance on a carer. Length of stay was not associated with unit of admission allowing for the variables described above. GER patients are a different population. They have more chronic illness and functional impairment, and are more likely to require multidisciplinary assessment and rehabilitation in addition to treatment of presenting illness. Elderly patients are appropriately referred by General Practitioners (GPs) without a formal admissions policy. PMID- 1506197 TI - The Chief Scientist reports.... Voluntary agency support for people with mental health problems. AB - The development of a cohesive support system is vital to the success of community based services and day care is an essential component of any system of support. McCreadie et al in a Scottish study of psychiatric hospital provision showed that while there was wide variation around Scotland in the provision of hospital based care, there was a general dearth of health service and local authority community based services. Philip and Stuckey in a survey of NHS long term non-resident patients of the Royal Edinburgh Hospital found that hospital staff felt that such patients would have benefited from additional daytime activity different from that provided in the health service. These authors found that some patients did make significant use of voluntary agencies, but were unable to elicit any systematic reasons for using or not using these agencies. Surveys in the statutory and voluntary sectors completed to date have tended to concentrate on the opinions of staff groups about the requirements and needs of clients. There has been no systematic survey of the facilities and opportunities most desired by users of voluntary sector support agencies. This survey, which received support from the Chief Scientist Organisation Mini-Project Scheme, aims to remedy this lack and to provide a factual basis from which the NHS, local authorities and voluntary agencies can draw, in their mutual aim of helping people with mental health problems. The results of the survey, while carried out in Edinburgh, may have relevance to planners and providers further afield in Scotland. PMID- 1506198 TI - [The effect of cosmetics and dermatologic agents on skin lipids]. AB - The composition of stratum corneum lipids and of sebum lipids is described with respect to their biological function, with special reference to dry skin. In this context, we discuss desiccation and lipid removal by surfactants and the protective and refatting effects of oil bath products and other lipid-containing preparations for topical use. PMID- 1506199 TI - [Osteoma cutis. Pathogenesis and therapeutic possibilities]. AB - No efficacious therapy for the treatment of increasing and spreading cutaneous ossification is yet established. We report a 52 year old white female with multiple miliary osteomas of the skin involving face, chest and back. The patient has a history of acne vulgaris. A therapeutic trial with a diphosphonate (etidronate disodium) was started in order to stop marked progression and appearance of new lesions. In accordance with the two previously described cases of the literature we failed to achieve any improvement. Clinical features, etiology, classification and therapy of osteoma cutis are discussed. PMID- 1506200 TI - [Sulzberger-Garbe exudative discoid and lichenoid chronic dermatosis ("Oid-Oid disease")--reality or fiction?]. AB - In 1937, Sulzberger and Garbe singled out an exudative discoid and lichenoid chronic dermatosis characterized by the combination of various symptoms which by themselves are not specific from the heterogeneous eczema group. The report of a 7-year-old girl is used as a basis to describe the characteristics of the disease and to present the authors' own interpretation. Clinically, there were discoid and lichenoid lesions with severe pruritus. Blood examination revealed eosinophilia. Histopathological examination of skin lesions showed psoriasiform, spongiotic, lichenoid dermatitis. A therapeutic regimen of oral corticosteroids led to complete regression of the skin changes. We feel that there are no clinical or histological findings to differentiate Sulzberger-Garbe disease definitely from extensive nummular eczema. PMID- 1506201 TI - [The growth modifying effect of wound ointments on cell cultures]. AB - Ointments are often used for the treatment of wounds with impaired healing or for patients with severe burning. Therefore, some information about their pharmacological effects is necessary. This paper presents an in vitro model for testing the effects of ointments on an isolated cell type with the possibility of quantification. In this study fibroblasts of the human gums and 12 ointments available without prescription were used. To investigate the toxic effects, we examined the morphological changes and autoradiography. The results and their clinical implications are discussed. PMID- 1506202 TI - [Eosinophilia-myalgia syndrome. Clinical aspects and follow-up of 10 patients]. AB - A retrospective study (1985-1989) of patients suffering from diffuse fasciitis with eosinophilia revealed that five of eight patients had taken L-tryptophan containing drugs before the onset of the disease. In addition, since this drug disease association was first described five patients have been diagnosed during the year 1990. All ten patients developed peripheral eosinophilia, myalgia and deep skin involvement indistinguishable from eosinophilic fasciitis. Corticosteroids were able to reduce the pain and inflammatory parameters, but did not prophylactically improve the long-standing sclerodermalike skin thickening. In 2/5 patients with symptoms longer than 1 year, low-dose corticosteroid maintenance therapy has been continuously required to control joint and muscle pain. PMID- 1506203 TI - [Multiple woolly hair nevi with linear epidermal nevus and persistent pupillary membrane]. AB - The woolly hair nevus is a very rare disease that only occurs sporadically. So far, approximately 48 patients with woolly hair nevus have been described in the world literature. Both sexes are equally affected. Mostly, the dermatosis manifests itself from birth or within the first 2 years of life. Up to 5 circumscribed areas with clearly lighter curly hairs can be observed. About 50% of the patients present a linear epidermal nevus at the same time. Microscopically, the hair shaft diameter of the woolly hair is significantly reduced. Next to oval structures the cross-sections of the hair often show triangular and irregular forms. Furthermore, pili canaliculi and pili torti as well as circumscribed cuticula defects can be observed. We present a 5-year-old boy, who manifested 4 woolly hair nevi on the capillitium in the 9th month of life. From the 2nd year of life onwards he developed a linear epidermal nevus. The ophthalmological examination showed a persistent pupillary membrane. Based on this case and a bibliographical overview, the light and electron microscopical peculiarities are presented. PMID- 1506204 TI - [Mycetoma with black granules: first case in a native of Israel]. AB - We present a case of black grain mycetoma caused by Madurella mycetomatis. The diagnosis was made on the basis of conventional light microscopy and mycological studies. After 12 months of oral therapy with ketoconazole, the patient showed partial response. This is the first native Israeli case of black grain mycetoma. PMID- 1506205 TI - [Botryomycosis caused by fusobacteria]. AB - In the Anglo-American literature botrymycosis is described as a chronic cutaneous granulomatous reaction to bacterial infection, containing granules resembling the sulphur granules seen in actinomycosis. The diagnostic and therapeutic aspects are discussed with reference to a recently observed patient. Fusobacterium nucleatum was isolated as the bacterial cause of the pathologic disorder. PMID- 1506206 TI - [Leukonychia longitudinalis as the primary symptom of Hailey-Hailey disease]. AB - Longitudinal white bands on the fingernails were observed in a 58-year-old male patient with perianal intertrigo. His nail changes were a first clue to the diagnosis of Hailey-Hailey disease, which was later confirmed histopathologically. Similar nail abnormalities were found in the patient's son who was also affected with Hailey-Hailey disease. These findings support the concept that those nail changes, first described by Burge in 1991, constitute a useful diagnostic marker in Hailey-Hailey disease. PMID- 1506207 TI - [Hutchinson-Gilford syndrome]. AB - A case report on a 6-year-old boy suffering from the extremely rare Hutchinson Gilford syndrome (progeria) is presented. The results of histopathological and immunohistological examination of the scar-like skin lesions are reported. Subcutaneous amorphous nodules were eosinophilic, PAS- und elastica-negative und remained unstained with antibodies against collagen type IV, vimentin, and collagenase. The dense perivascular infiltration consisted of CD4+, CD8-, alpha-1 antichymotrypsin-, MAC 387-, and some vimentin-positive cells. Perinodular blood vessels were more abundant and had a thickened wall. Collagen bundles were swollen. The epidermis appeared atrophic with focal basal cell degeneration. PMID- 1506208 TI - [Age-dependent therapeutic response of plantar warts]. PMID- 1506209 TI - [Mobiluncus as the pathogen in a sexually transmitted disease]. PMID- 1506210 TI - [Prevention and therapy of decubitus ulcer]. PMID- 1506211 TI - [Chemically-induced scleroderma]. AB - Scleroderma-like diseases can be induced by a number of chemical compounds, such as plastics, solvents and drugs. Contaminated rapeseed oil was the cause of the toxic oil syndrome and L-tryptophan induces the so-called eosinophilia-myalgia syndrome. On the other hand, paraffin and silicon can trigger so-called adjuvant disease, while long-term exposure to silica can lead to idiopathic scleroderma (associated with silicosis in some cases). In addition to the clinical features, some pathogenetic data in the literature, such as genetic factors (HLA, chromosomal anomalies, enzyme deficiencies) and the metabolism of chlorinated ethylenes via reactive epoxide intermediate products, and our own findings are reported. Silica-induced scleroderma cannot be distinguished from the idiopathic form by epidemiological, clinical or immunological studies or by parameters referring to the blood vessels or collagen metabolism. In cell culture studies it has been shown that macrophages/monocytes release IL1, IL6 and TNF after ingestion of silica, which affects fibroblasts, T-helper cells and endothelial cells. Comparative results from the silicosis literature are reported. Finally, the possibly stimulating role of ionizing irradiation (uranium mining) in favouring the development of scleroderma is discussed. PMID- 1506212 TI - [Homeopathy. Basic aspects and principles of use in dermatology]. AB - Homoeopathy was established in 1796 by Samuel Hahnemann (1755-1843). This method is an alternative form of therapy involving treatment by natural remedies. The basic principles of homoeopathic medicine, "similia similibus curentur", "experimenta in homine sano", "doses minimae" and "unitas remedii", are founded upon the idea of illness as a disorder of the internal equilibrium at the physical, mental and psychic levels. The entire picture of symptoms is ascertained in each individual case by scrupulous history taking. A remedy which provokes a similar picture of effects in healthy persons is finally employed as the homeopathic therapeutic agent (law of similars). According to the homoeopathic view, skin diseases are manifestations of an internal or constitutional disorder. Thus, homoeotherapy of skin diseases is based on morphological, local and constitutional criteria. PMID- 1506213 TI - [The possible nephrotoxicity of a bituminous coal dermatologic agent]. AB - Nephrotoxic effects are discussed as a possible risk of dermatological coal tar preparations. Therefore, we have performed a renal tolerance study with a modern coal tar preparation for the scalp, Berniter. 15 healthy volunteers, randomly subjected to 3 different modes of application, applied the preparation: twice weekly (mode I) or daily (mode II) for a period of 8 weeks. In both modes, application time was 15 min. In mode III, the preparation was used under occlusion for 30 min every second day for a period of 4 weeks. Before, during and after treatment, renal functions and urinary phenol levels were assayed. No pathological change or impairment of renal functions was detected. A relationship between urinary phenol content and the coal tar treatment was not observed, either. We conclude that the coal tar preparation investigated here has no nephrotoxic properties. PMID- 1506214 TI - [Epiluminescent microscopy score for differential diagnosis of dysplastic nevi]. AB - Specific epiluminescent microscopical criteria of histopathologically defined dysplastic nevi are yet unknown. The diagnostic evaluation of dysplasia and atypia is especially based on microscopic assessment of combined morphologic and coloured details of melanocytic lesions. Differences, skin microscopically analysed, between a group of 55 dysplastic nevi and a comparative group of 130 junctional and compound nevocellular nevi were statistically significant for 12 characteristics. Thus a score could be established for surface microscopic differential diagnosis of dysplastic nevi. PMID- 1506215 TI - [Unilateral lentiginosis--a segmental neurofibromatosis without neurofibromas]. AB - Segmental neurofibromatosis (NF) is a usually non-inherited form of NF that is characterized by unilateral neurofibromas and/or cafe-au-lait spots. In partial unilateral lentiginosis (PUL), apart from unilateral lentigines, cafe-au-lait spots of different dimensions have been described in some patients without fulfilling the diagnostic criteria for NF. We report on three patients representing the 4th to 6th cases of segmental NF without neurofibromas. The diagnosis resulted from unilateral cafe-au-lait spots of different sizes in all patients and axillary "freckling" and associated skeletal alterations in two patients each. As these findings are clinically and histologically comparable to reported cases of PUL and moreover fulfil the diagnostic criteria for segmental NF, our cases support the hypothesis that PUL is a segmental NF lacking neurofibromas. PMID- 1506216 TI - [Family study of erythrokeratodermia figurata variabilis]. AB - Erythrokeratodermia figurata variabilis (EKV) is a rare disorder of cornification inherited as an autosomal dominant trait. Genetic linkage to the Rh locus on chromosome 1 has been recently documented. In 1957, Sommacal and Schnyder reported on a family with 14 affected members. We have reexamined this pedigree, which counts 77 members with 29 affected persons over five generations (45 females, 31 males). Twenty females and 9 males were affected. In all patients EKV presented in the first year of life, and several mothers noted the erythematous lesions at birth of their children. The hyperkeratotic lesions appeared later. The reddish macules changed within hours to days. The erythematous areas were sharply outlined and sometimes surrounded by an anemic border. Only few members stated that their erythema could persist for more than a week. Clear triggers were emotional stress and changes of temperature. In all but two of the patients erythema was prominent and in the others hyperkeratotic lesions were more severe. Most patients had a burning sensation in their red areas. There was a marked tendency for improvement of EKV after puberty. Five females reported regular superficial skin peeling on hands and feet. The features in these patients had some similarities with erythrokeratolysis hiemalis. PMID- 1506217 TI - [Loose anagen hair]. AB - We report on a 5-year-old girl whose hair could be pulled out with no effort and without causing pain. Occipital alopecia in a patchy pattern and with no sign of scalp inflammation or scarring was noted. A trichogram from the clinically involved area disclosed a striking predominance of anagen hair with absence of external root sheaths. Histological examination of the hair suggests abnormal premature keratinization of the inner root sheath, resulting in the loss of its anchoring function between the hair shaft and the follicle. Zaun first reported this new type of hair loss in children in 1984. The name loose anagen hair of childhood has recently been suggested for this disease. The differential diagnosis includes alopecia areata, trichotillomania, and congenital hypotrichosis. PMID- 1506218 TI - [Curling and kinking of hair caused by etretinate]. AB - In two female psoriasis patients, curling and kinking of the scalp hair developed subsequent to a long-term etretinate therapy. Scanning electron microscopic examination of kinking hair revealed twists with sharp-edged defects and splitting of the cuticle cells in several hairshafts. The quantitative determination of the mechanical parameters of these hairs using a computerized system revealed statistically significant changes from the pattern in the scalp hair of untreated psoriasis patients. This finding suggests etretinate-induced alteration of the expression of the psoriatic phenotype in the keratin composition of hair in psoriasis patients. PMID- 1506220 TI - [UV-A treatment of psoriatic arthritis]. PMID- 1506219 TI - [Grouped and combined blue nevi]. AB - The simultaneous occurrence of blue and naevocytic naevus in the same lesion is rare and can be difficult to diagnose. Precise differentiation from nodular melanoma may only be possible by histopathological examination. Agminated blue naevi, first described by Upshaw et al. [25] in 1947, are also rare. It is important to differentiate these lesions from nodular melanoma with satellite metastases. We describe two patients with such unusual blue naevi. PMID- 1506221 TI - [Dermatoses in the diaper area]. PMID- 1506222 TI - North of the border. PMID- 1506223 TI - Taking up the challenge of change. Interview by Cath Jackson. PMID- 1506224 TI - Breastfeeding. Setting a standard: the challenge for health visiting. AB - Health visitors agree that breast is best. But how far is this principle translated into practice? Copious evidence exists of conflicting advice and views on breastfeeding among health professionals and even between health visitors themselves. Marianne Cowpe, Ann MacLachlan and Elizabeth Baxter describe how north east Fife health visitors drew up an agreed standard of practice to boost local breastfeeding rates. PMID- 1506225 TI - Breaking down the barriers. AB - In theory, health visitors support a social model of health. But the reality of their practice is very different. Drawing on her own experience in a health visiting community development post, Yvonne Dalziel argues that constraints to this new way of working can be overcome. PMID- 1506226 TI - Games health visitors play: interaction on home visits. AB - Health visitors routinely use a number of verbal ploys to control and direct interactions with clients. Shona Cameron describes some of the findings of a recent study of conversations between health visitors and clients on home visits. PMID- 1506227 TI - Proactive health visiting in Falkirk. AB - Isolation and low morale prompted health visitors in Forth Valley health board to set up a group which could work together proactively at a time of uncertainty and change. Sally Johnson describes the group's beginnings and achievements so far. PMID- 1506228 TI - The children's hearing system and the health visitor's role. AB - Scotland's legal system is widely acknowledged to deal more sensitively with child protection cases. Here Karen Devlin describes the children's hearing system and discusses the role of the health visitor working with families in crisis and coming before a panel hearing. PMID- 1506229 TI - Implementing an annual screening programme. AB - Anna May describes a programme to screen annually the health of people over 75 on her caseload and the opportunities it offers for active health promotion. PMID- 1506230 TI - The new face of family law in Scotland. PMID- 1506231 TI - Avoiding the poverty trap. PMID- 1506232 TI - Clearing the air. PMID- 1506233 TI - Enzyme histochemistry and immunohistochemistry with freeze-dried or freeze substituted resin-embedded tissue. AB - Freeze-drying or freeze-substitution, combined with low-temperature resin embedding, represents a new approach to the optimum preservation of tissue for enzyme histochemistry and immunohistochemistry. This method, which avoids tissue fixation, combines excellent tissue morphology with the preservation of enzyme activity and immunoreactivity and allows high-resolution enzyme histochemical and immunohistochemical studies to be performed. The activity of a wide range of enzymes can be demonstrated in sections of freeze-dried or freeze-substituted resin-embedded tissue. Enzymes are retained in situ with high activity, accurate localization and no diffusion. Immunohistochemical studies can also be performed on resin sections, and antigens--especially labile antigens--are immobilized in situ without denaturation and can be demonstrated with high sensitivity and accurately localized. This method allows the localization and distribution of enzymes and antigens to be studied in relation to excellent histological and cytological detail. PMID- 1506235 TI - Cationic colloidal gold--a probe for light- and electron-microscopic characterization of acidic glycoconjugates using poly-L-lysine gold complex. AB - Cationic colloidal gold (CCG) was used to characterize acidic glycoconjugates in semithin and ultrathin sections of rat large intestine and salivary glands embedded in hydrophilic Lowicryl K4M resin. It was prepared from poly-L-lysine and 10 nm colloidal gold solution. The staining of CCG in semithin sections was amplified after photochemical silver reaction using silver acetate as a silver ion donor and examined under bright-field and epi-illumination microscopy. CCG adjusted to various pH levels was tested on various rat tissues whose histochemical characteristics with regard to acidic glycoconjugates are well known. At pH 2.5 CCG labelled tissues containing sialylated and sulphated acidic glycoconjugates such as the apical cell surface, mucous cells in the distal and proximal colon, and acinar cells of the sublingual gland. In contrast, CCG at pH 1.0 labelled tissues containing sulphated acidic glycoconjugates such as mucous cells in the upper crypt of the proximal colon and mucous cells in the whole crypt of the distal colon. This specificity of CCG was verified by the alteration of CCG staining following several types of cytochemical pretreatment. These results were further confirmed by electron microscopy. CCG staining is thus a useful postembedding procedure for the characterization of acidic glycoconjugates at both the light- and electron-microscopic levels. PMID- 1506234 TI - Light-microscopic detection of acidic glycoconjugates with sensitized diamine procedures. AB - To enhance the efficiency and specificity of diamine methods in light microscopy, these methods were sensitized by silver enhancement in combination with trichloro(ethylene) platinate (KTP). The sensitized diamine methods consisted of a diamine (high or low iron diamine: HID or LID), KTP, borohydride reduction (BH) and a physical development (PD) sequence. The new methods have been successfully applied to routinely prepared tissue sections obtained from rat organs, such as salivary glands, stomach, colon, kidney, lung and trachea. In the tissues subjected to the sensitized diamine methods, weakly diamine-stained histological structures exhibited vivid positive reactions. The combined sensitized diamine methods and selective procedures, such as enzyme digestion and chemical modification, have substantiated that these methods were of sufficient efficiency and specificity. PMID- 1506236 TI - Species differences in adenosine metabolic sites in the heart. AB - 5'-Nucleotidase and purine nucleoside phosphorylase, two key enzymes in nucleoside metabolism, have been localized electronmicroscopically in left ventricular myocardium of the human, dog, pig, rabbit, guinea pig and rat. Ectonucleotidase activity was present in all species at the plasma membrane of pericytes. Reactive endothelial cells in the microcirculatory bed were restricted to those covering resistance arterioles. Cardiomyocytes were reactive only in the rat. Purine nucleoside phosphorylase was localized uniformly in the vascular endothelium of all species. The strongest activity was seen in the pericytes of guinea pig, rat and dog. Pericytes of rabbit and pig were virtually unreactive, whereas a minority of cells in human samples were positive. Cardiomyocytes were unreactive in all species. These variations in the distribution pattern of adenosine metabolic sites may have definite consequences for disposal and recovery of adenylates and their breakdown products in ischaemia and for the effects to be expected from interference with nucleoside transport inhibition. PMID- 1506237 TI - A dot blot technique for the analysis of interactions of lectins with glycosaminoglycans. AB - Glycosaminoglycans are polysaccharides which are widely distributed throughout connective tissue, where they form an essential part of the extracellular matrix. Connective tissue is often stained by lectins, and it is not known whether this staining is due to the interaction of lectins with the glycosaminoglycans or due to the binding of lectins to other glycoconjugates within the matrix. A dot blot technique is presented by which the interaction of lectins with glycosaminoglycans can be analysed. PMID- 1506238 TI - Freedom of Information Act does not provide full disclosure. PMID- 1506239 TI - Ignoring business regulations can be hazardous to your practice. Concerns facing the profession. PMID- 1506240 TI - Wolf hybrids--a biological time bomb? PMID- 1506241 TI - Communicate to avoid malpractice claims. PMID- 1506242 TI - Virology as the cornerstone of a memorable career. PMID- 1506243 TI - Court modifications of covenants against competition. PMID- 1506245 TI - Comparison of applanation tonometers in dogs and horses. AB - Two Mackay-Marg tonometers and 2 Tono-Pen tonometers were evaluated in eyes in which intraocular pressure (IOP) had been altered and measured by use of a manometer. Eyes of anesthetized dogs and enucleated horse eyes were used. Compared with the manometer, none of the tonometers accurately measured IOP over the range between 0 and 100 mm of Hg. However at manometer measurements from 0 to 30 mm of Hg, several of the tonometers accurately measured IOP. In addition, significant differences were observed when the measurement accuracy of one tonometer was compared with that of another, especially at high IOP. Coefficient of determination (r2) values for a linear model ranged from 0.979 to 0.991 in dogs, and from 0.982 to 0.996 in horse eyes. PMID- 1506244 TI - Immunogenicity and efficacy study of a commercial Borrelia burgdorferi bacterin. AB - The immunogenicity and efficacy of a commercial Borrelia burgdorferi bacterin was evaluated for stimulation of the host immune response and protection against clinical disease associated with experimentally induced borreliosis in dogs. A total of 30 vaccinated and 24 control dogs were used in 3 separate studies. The vaccine was given IM as two 1-ml doses separated by a 3-week interval. Two weeks or 5 months following the last vaccination, the dogs were challenge inoculated with 7 daily doses of a virulent preparation of a B burgdorferi field isolate through intraperitoneal, subcutaneous, and intradermal routes with or without glucocorticoid administration at the same time. The development of B burgdorferi spirochetemia and clinical disease in the dogs after challenge exposure was studied. Serum samples were obtained from the dogs at various times during the study for serum neutralizing antibody determination and protein immunoblot antibody assay against various geographic isolates of B burgdorferi. Challenge exposure induced limb/joint disorder, fever, anorexia, signs of depression, and B burgdorferi spirochetemia in the nonvaccinated control dogs. The vaccine was found to elicit cross-reactive serum neutralizing and protein immunoblot antibody responses in dogs to various isolates of B burgdorferi and to protect the vaccinated dogs against experimentally induced borreliosis. PMID- 1506246 TI - Plasma concentrations of 13,14-dihydro-15-ketoprostaglandin F2 alpha in mares during uterine involution. AB - Twelve mares were allowed to foal naturally, after which they were monitored to study uterine involution. Starting on day 3 after parturition, the internal genital tract was examined per rectum manually and ultrasonographically every other day for changes in uterine characteristics and ovarian activity. By day 5, gravid and nongravid uterine horns were similar in size, and by day 7, uterine fluid was absent. On day 7 after parturition, endometrial biopsy samples were obtained for histologic evaluation, and uterine swab specimens were obtained for microbiologic culture. Uterine swab specimens from 10 of 12 mares had slight bacterial growth. The uteri of 8 of the 12 mares were histologically involuted by day 7. All mares ovulated 7 to 12 days after parturition. Concentrations of 13,14 dihydro-15-keto-PGF2 alpha (PGFM) were measured in jugular plasma samples obtained daily for 21 days after parturition. Concentrations of PGFM were low by the day after parturition, and there was no significant correlation between uterine involution and PGFM concentrations in these mares. All 12 mares were bred at the first estrus after parturition, and 9 became pregnant. PMID- 1506247 TI - Effect of repeated collection of multiple endometrial biopsy specimens on subsequent pregnancy in mares. AB - Endometrial biopsy specimens (4 or 5 on each occasion) were collected from 7 mares 2, 3, or 4 times over a 50-day period prior to breeding. Four of the collection days were within 6 days of breeding. Six of the 7 mares were diagnosed as pregnant by use of ultrasonography at day 14 after ovulation. This pregnancy rate was the same as that achieved by these mares when they were bred at estrus before the start of the study. It appeared that repeated collection of multiple endometrial biopsy specimens from genitally normal mares did not adversely affect pregnancy rate. PMID- 1506248 TI - Milk production, water consumption, and somatic cell count responses of cows subject to one to two volts of alternating current. AB - A dairy farm located in central New York was visited because of complaints of electrical shock in the farmhouse shower and the milk house sink. As much as 2 volts AC of potential difference was measured between the waterline and the cow platform (cow-contact voltage). Voltage was coming from the primary neutral wire. The farm's electrical service was modified so that the farmstead could be connected or disconnected from the primary neutral wire at 2-week intervals for 12 weeks. When connected to the primary neutral wire, voltage between waterline and floor ranged between 0 and 1.8 volts, producing estimated current flow through cows of 3.6 to 4.9 mA; when disconnected from primary neutral wire, voltage between waterline and floor was less than 0.1 volt. There was no difference in mean milk production, bulk tank milk somatic cell count, or water consumption among periods when cows were exposed or unexposed to voltage. Despite statistical nonsignificance, the values for somatic cell count were lower and water consumption was higher when cows were exposed to voltage than when they were not. PMID- 1506249 TI - Colostral transfer of Bacteroides nodosus antibodies in sheep. AB - Ovine contagious foot rot may cause lameness in sheep, resulting in decreased wool growth and low weight gain. Affected neonatal lambs are difficult to treat, and treatment is labor intensive; thus, a method of prevention is warranted. Vaccination of ewes with a multivalent vaccine in an oil adjuvant induced development of antibody to the somatic O antigen of Bacteroides nodosus, and this antibody was detected in serum of newborn lambs after consumption of colostrum from the vaccinated ewes. Antibody titers were determined in 48 unvaccinated ewe/lamb pairs, and in 50 once-vaccinated and 78 twice-vaccinated pairs. Serum and colostrum O-agglutinin titers to B nodosus were determined by a microtitration agglutination test. Lambs from vaccinated ewes had significantly (P less than 0.05) higher O-agglutinin titers than those from unvaccinated ewes, and double vaccination of ewes resulted in the highest potentially protective titers (greater than 1:2,400) in ewes and lambs. PMID- 1506251 TI - Resection and anastomosis for treatment of strangulating volvulus of the large colon of horses. AB - Strangulating volvulus of the large colon was treated by resection and anastomosis of the colon in 9 horses. Tissue specimens were obtained at the site of the resection for histologic evaluation. An attempt was made to correlate the appearance of the colon at the time of surgery to the histologic evaluation and the eventual outcome. Six of the 9 horses (66%) survived. This is in contrast to a reported survival of 34.7 to 36% after decompression and reduction of colonic volvulus. Survival after surgery could not be predicted on the basis of visual assessment or histologic examination. PMID- 1506250 TI - Comparison of anthelmintic control programs for sheep in Virginia. AB - Haemonchus contortus is the most serious parasitic problem encountered by sheep producers in southwestern Virginia. Four anthelmintic control programs for grazing lambs were tested. Group TR received monthly SC injections of ivermectin (200 micrograms/kg of body weight). Group SI received the same dose of ivermectin at 0, 3, 6, 9, and 12 weeks after the start of the grazing season. Group SL was given levamisole (8 mg/kg, PO) 0, 3, 6, 9, and 12 weeks after the start of the grazing season, and group TA received ivermectin (200 micrograms/kg) 0, 8, 16, 20, and 24 weeks after the beginning of grazing. None of the 4 programs provided satisfactory control of parasites as indicated by fecal egg counts and serum pepsinogen concentrations, although group-TR lambs gained significantly more weight than lambs in groups SI and TA. Group-TA lambs developed clinical haemonchosis in early August and required additional treatment at that time. These findings suggest that reliance on anthelmintics alone may not provide the most effective and economic control of parasitic infection. PMID- 1506252 TI - Septic peritonitis associated with caudal myotomy in a Tennessee walking horse. AB - A 2-year-old Tennessee Walking Horse colt was admitted for evaluation of signs of abdominal pain, inappetence, and constipation of 5 days' duration. Two days prior to the onset of signs, the owner had cut the sacrococcygeal muscles as part of a tail-setting procedure. On examination, the horse was febrile and lethargic, and intestinal sounds were not heard on auscultation. Results of peritoneal fluid analysis were indicative of peritonitis. The horse continued to deteriorate and died despite treatment with antimicrobials, flunixin meglumine, and balanced electrolyte solution. At necropsy, the peritoneal cavity contained approximately 20 L of serosanguineous fluid. One of the myotomy wounds was filled with yellow green material that extended from the base of the tail along the ventrolateral aspect of the rectum and into the peritoneal cavity. Escherichia coli was isolated from the myotomy site and peritoneal fluid. PMID- 1506253 TI - Laryngeal granuloma in a bull. AB - Dyspnea in an adult bull caused by a large laryngeal granuloma was corrected by use of a surgical technique that allowed resection of the mass without ventral laryngotomy. Endoscopy was used for visualization of the mass during the oral surgery. The technique may be performed in the field. PMID- 1506254 TI - Adenocarcinoma of the middle ear with osteolysis of the tympanic bulla in a cat. AB - Peripheral vestibular disease and lethargy were attributed to an adenocarcinoma in the middle ear of a 10-year-old cat. The tumor was invasive, inducing severe lysis of the tympanic bulla and adjacent temporal bone. Direct invasion to the meninges and brainstem also was observed. Neoplasms of the middle ear are rare in cats, with squamous cell carcinomas reported most commonly, but should be considered as causes of chronic otitis or signs of peripheral vestibular disease. PMID- 1506255 TI - Pancreatic adenocarcinoma with metastasis in two ferrets. AB - Exocrine pancreatic adenocarcinoma with carcinomatosis was diagnosed in 2 ferrets. Clinical signs included abdominal distention and hind limb weakness. Ultrasonography revealed moderate ascites in both ferrets, an irregular abdominal mass in 1 ferret, and multiple abdominal masses in the other ferret. The ferrets were euthanatized, and necropsy of 1 ferret revealed carcinomatosis without visceral metastasis. PMID- 1506256 TI - Bromide toxicosis (bromism) in a dog treated with potassium bromide for refractory seizures. AB - A 4-year-old German Shepherd Dog was evaluated because of chronic hind limb lameness and recurrent seizures. Diagnostic evaluation of the dog confirmed rheumatoid arthritis and idiopathic epilepsy. The rheumatoid arthritis was treated with prednisone and piroxicam. The seizures were treated with phenobarbital plus clonazepam. The seizures were refractory and potassium bromide was substituted for clonazepam. The dog was reevaluated 4 months after initiation of potassium bromide treatment because of recurrence of arthritis signs. During hospitalization, the dog had neurologic signs, which progressed from depression to recumbency and stupor. Anisocoria, muscle pain, and hyporeflexia were noticed. Bromide toxicosis was diagnosed on the basis of toxic serum bromide concentration (2.7 mg/ml; therapeutic range, 1.0 to 2.0 mg/ml). Following cessation of potassium bromide treatment, the neurologic signs resolved. The seizures recurred 6 weeks after potassium bromide was discontinued. Bromide treatment was reinitiated at half the initial dosage. After 6 weeks, the serum bromide concentration was 1.9 mg/ml, and no seizures had been reported by the dog's owners. Therapeutic serum bromide concentrations in dogs has been reported to be 0.5 to 2.3 mg/ml. The serum bromide concentration at which toxic signs are expected is variable in human beings because individuals differ in their tolerance of the drug. Clinical trials are necessary to determine the toxic serum bromide concentrations in dogs. This case of bromism in a dog suggests that the dosage of potassium bromide should be based on serial measurement of serum bromide concentrations. PMID- 1506257 TI - Morbidity and mortality in pups from pet stores and private sources: 968 cases (1987-1988). AB - Morbidity (greater than or equal to 1 disease condition) for pups sold from 3 pet stores from January 1987 through December 1988 ranged from 54 to 68%. In 1 store, morbidity was higher for store pups, compared with pups originating from private parties, for such disease conditions as "kennel cough," diarrhea, and several species of gastrointestinal parasites. In-store mortality ranged from 5 to 9.5% of pups arriving for sale. PMID- 1506258 TI - Nonsteroidal anti-inflammatory drug toxicosis in dogs and cats: 240 cases (1989 1990) AB - A search of medical records at the Georgia Animal Poison Information Center over a 19-month period revealed 240 cases of dog and cat exposure to nonsteroidal anti inflammatory drugs (NSAID). The most common NSAID consumed were ibuprofen, acetaminophen, aspirin, and indomethacin. The most common clinical signs of toxicosis were vomiting and diarrhea, CNS depression, and circulatory manifestations. Pets are at risk from NSAID toxicosis through administration by the owners or accidental consumption of improperly stored drugs. PMID- 1506259 TI - Clinical and laboratory findings associated with actual or suspected azoospermia in dogs: 18 cases (1979-1990). AB - Eighteen dogs were evaluated for azoospermia, 8 of which had sired pups. On the basis of history, physical examination, and various laboratory evaluations, the cause and site of azoospermia varied. Two dogs that had never sired pups had likely been azoospermic from puberty (congenital azoospermia). Two dogs were azoospermic as a result of tumors (Sertoli cell tumor and malignant astrocytoma of the pituitary gland). Deposits of IgG were observed in testicular biopsy samples, which suggested an auto-immune cause for azoospermia in 5 dogs. One of the 5 dogs with IgG deposits in testicular tissues also had evidence of immune mediated thyroiditis. Culturing of microbes in the semen was not helpful in determining potential causes of azoospermia, and results did not correlate with organisms isolated from testicular biopsy samples or with the finding of inflammation in biopsy samples. Because 6 dogs had relatives with histories of reproductive dysfunction, inbreeding also must be considered when evaluating dogs for azoospermia. PMID- 1506260 TI - Complications of nasogastric intubation in horses: nine cases (1987-1989). AB - Pharyngeal or esophageal trauma was diagnosed in 9 horses after nasogastric intubation. Evidence of trauma (edema or ulceration) was detected in the pharynx of 3 horses and in the esophagus of 6 horses. Complications associated with nasogastric intubation were first observed in 5 horses while they were intubated and in 4 horses after extubation. Clinical signs of pharyngeal or esophageal trauma were similar, and included salivation, bruxism, coughing, and nasal discharge. Treatment, including extubation, enteral feeding through a small nasogastric tube, or esophagostomy distal to the affected site, was attempted in 6 horses. Three of 6 treated horses survived, but 4 of 5 horses with perforated esophagus were euthanatized. PMID- 1506261 TI - Effects of sulfate in drinking water for livestock. PMID- 1506262 TI - What is your diagnosis? Diaphragmatic hernia in a horse. PMID- 1506263 TI - Poly ADP-ribosylation reaction. PMID- 1506265 TI - A novel tetracyclic peptide, trapoxin, induces phenotypic change from transformed to normal in sis-oncogene-transformed NIH3T3 cells. AB - A novel tetracyclic peptide, trapoxin [cyclo(L-phenylalanyl-L-phenylalanyl-D pipecolinyl-L-2-amino-8-oxo -9,10-epoxy - decanoyl)], was found to induce the flat phenotype in v-sis-transformed NIH3T3 cells at a quite low concentration of 1 ng/ml. Actin stress fiber could be detected after trapoxin treatment. Almost complete reversion into the flat phenotype was observed at 6 h after the administration of the compound. The effect of trapoxin was reversible, when the cell culture was incubated for more than 24 h after its removal. The intracellular level of sis-mRNA did not decrease with trapoxin treatment at a concentration (50 ng/ml), sufficient to reverse the transformed morphology. Substitution of pipecolinic acid with proline in trapoxin did not change the activity. WF3161, in which leucine was substituted for a phenylalanine of trapoxin, showed only one-sixteenth of the activity of trapoxin. Reduction of the epoxide residue of trapoxin destroyed the activity. PMID- 1506264 TI - Successful graft of HTLV-I-transformed human T-cells (MT-2) in severe combined immunodeficiency mice treated with anti-asialo GM-1 antibody. AB - To develop an experimental model of adult T-cell leukemia/lymphoma in small animals, severe combined immunodeficiency (SCID) mice treated with anti-asialo GM 1 antibody were inoculated with MT-2 cells, a cell line transformed by the human T-cell leukemia virus (HTLV-I). Three mice injected with 4 x 10(7) cells subcutaneously or intramuscularly developed tumors at or near inoculation sites. Immunofluorescent antibody (IFA) staining for HTLV-I structural protein, p19, revealed the specific antigen in the cytoplasm of most cells from tumors and the DNA signals of HTLV-I proviral DNA were also positive in cellular DNA by polymerase chain reaction assay with HTLV-I tax gene primers, SK43/SK44. The MT-2 cells did not invade in mouse organs. PMID- 1506266 TI - Second primary cancer following laryngeal cancer with special reference to smoking habits. AB - The risk of developing a second primary cancer following laryngeal cancer was estimated by following-up 472 male laryngeal cancer patients for an average of 8.6 years by means of record linkage to the Osaka Cancer Registry. Of these patients, 115 developed a second cancer other than laryngeal cancer, whereas the expected number derived from the incidence rates among Osaka residents was 51.4 (relative risk (RR) = 2.2, 95% confidence interval = 1.85-2.69). Cumulative risk of developing a second primary cancer was estimated to be 31.1% at 15 years after laryngeal cancer. By site, the risks were significantly increased for tobacco related cancers, RR = 24.5, 6.1 and 2.3 for cancers of the oral cavity & pharynx, esophagus and lung, respectively. Also, the risks were higher among heavy smokers for cancer of the oral cavity & pharynx and esophagus than among light smokers. No adverse effects of radiotherapy for laryngeal cancer on the development of thyroid cancer, lymphoma and leukemia were observed. The present study suggests the necessity of following-up laryngeal cancer patients over a long period in order to enable the early detection of tobacco-related cancer. PMID- 1506267 TI - Illiteracy, ignorance, and willingness to quit smoking among villagers in India. AB - During the field work to control oral cancer, difficulty in communication was encountered with illiterates. A study to define the role of illiteracy, ignorance and willingness to quit smoking among the villagers was undertaken in a rural area surrounding Doddipatla Village, A.P., India. Out of a total population of 3,550, 272 (7.7%) persons, mostly in the age range of 21-50 years, attended a cancer detection camp. There were 173 (63.6%) females and 99 (36.4%) males, among whom 66 (M53 + F13) were smokers; 36.4% of males and 63% of females were illiterate. Among the illiterates, it was observed that smoking rate was high (56%) and 47.7% were ignorant of health effects of smoking. The attitude of illiterate smokers was encouraging, as 83.6% were willing to quit smoking. Further research is necessary to design health education material for 413.5 million illiterates living in India (1991 Indian Census). A community health worker, trained in the use of mass media coupled with a person-to-person approach, may help the smoker to quit smoking. PMID- 1506268 TI - The effect of breast self-examination on early detection and survival. AB - To investigate the effect of breast self-examination (BSE), we compared the stages, survival, and the risk of death for 355 patients with breast cancer detected by BSE with those for 1,327 patients with breast cancer detected by chance. The early stages of the disease were found to be more common among the symptomatic breast cancer patients detected by BSE than those by chance. The 5 year overall survival rate was 94.4% for the symptomatic patients detected by BSE, and was significantly higher by 8.7% than that (85.7%) for patients detected by chance (P less than 0.001). The 10-year survival rate was 81.6% for patients detected by BSE, and 76.6% for cases detected by chance (the difference was not significant). The overall difference between the two survival curves was statistically significant by the logrank test (P less than 0.01). A multivariate analysis using the Cox proportional hazards model showed that the risk of death for patients detected by BSE was smaller by 0.570 times than that for patients detected by chance, which was statistically significant (P less than 0.05). The effect of biases inherent to BSE in the survival analysis cannot be controlled completely even after conducting multivariate analysis. These results suggest that BSE may contribute to the reduction of the risk of death through early detection of breast cancer. However, further examination should be conducted by other methods to obtain conclusive evidence. PMID- 1506269 TI - Ubiquitous presence in mammalian cells of enzymatic activity specifically cleaving 8-hydroxyguanine-containing DNA. AB - Here we report the finding of enzymatic activity that specifically cleaves DNA containing 8-hydroxyguanine (oh8Gua) residues in various mammalian cells. To detect this activity, we used a synthetic double-stranded DNA containing a single oh8Gua at a defined position as the substrate, and analyzed the products of enzymatic digestion by polyacrylamide gel electrophoresis. Two cleavage sites near the oh8Gua residue were detected with partially purified fractions from cow brain and rat liver, and also with preparations from all mammalian tissues examined. These results suggest that enzymatic activity for the removal of oh8Gua from DNA is widely distributed in mammalian cells. PMID- 1506270 TI - Growth inhibition by anchorage-deficiency is associated with increased level but reduced phosphorylation of mutant p53. AB - Human breast carcinoma MCF-7 cells seeded on type I collagen-coated dishes were provided with an anchor via the collagen receptor, integrin, and grew as actively as those in plastic tissue culture dishes. In contrast, cells seeded on a layer of soft agar became anchorage-deficient and their growth was significantly inhibited, although the cell viability and the cell cycle distribution were unaffected. Immunoprecipitation analysis revealed that mutant p53 was phosphorylated at tyrosine in the anchorage-provided cells. In contrast, the p53 in the anchorage-deficient cells was present in 2-fold greater amount, but was phosphorylated to a lesser extent. Addition of a potent protein-tyrosine kinase inhibitor, herbimycin A, to the anchorage-provided cells caused an elevated level of p53, and inhibitions of cell proliferation and p53 phosphorylation, without interfering with the cell adhesion to the substratum. These results demonstrated that the growth inhibition by anchorage-deficiency or by herbimycin A is associated with an elevated p53 level and reduced p53 phosphorylation at tyrosine. PMID- 1506271 TI - Soluble interleukin-6 receptor is released from receptor-bearing cell lines in vitro. AB - Soluble interleukin-6 receptor (sIL-6R) was found to be spontaneously released from human myeloma cell line U266 cells into culture supernatant, and was quantitatively measured with a fluorescence sandwich enzyme-linked immunosorbent assay employing antibodies specific to IL-6R. The supernatant IL-6R was generated only from IL-6R-positive cell lines; myeloma cell lines RPMI8226 and PRMI1788, and myelomonocytic cell lines U937, THP-1, and HL-60. In contrast, it was not released from the IL-6R-negative cells; T cell line Molt-4 and Burkitt lymphoma cell line Raji. SDS-PAGE analysis of the soluble IL-6R from U266 cells suggested a molecular weight of approximately 50-55 kDa, 25-30 kDa smaller than the mature cell surface receptor. These results suggest that the generation of soluble IL-6R may be a maker of myeloma cells and myelomonocytic cells. PMID- 1506272 TI - Autoradiographic analysis of radiolabeled anti-carcinoembryonic antigen monoclonal antibody CEA102 in colorectal cancer using computed radiography. AB - Anti-carcinoembryonic antigen monoclonal antibody (MAb) CEA102 was produced by immunization with purified CEA and the specific accumulation of radiolabeled CEA102 in colorectal cancers was investigated by autoradiography of surgical specimens using Fuji Computed Radiography (FCR). Five patients with colorectal cancer were injected intravenously with 131I-labeled intact CEA102 or its F(ab')2. Primary tumor and liver metastases were successfully detected by external scanning with a gamma camera in 4 cases. Autoradiographic study of the surgical specimens using FCR showed predominant localization of 131I-labeled CEA102 in primary tumors and liver metastases in all cases. Even a small liver metastasis (0.5 cm) was clearly visualized in the autoradiogram by FCR. The pixel distribution curves of the density of the respective tissues in the autoradiograms by FCR showed the heterogeneity of the distribution of administered radiolabeled MAb in individual tumors, but the density of the tumors was higher than that of the normal tissues. In the quantitative distribution analysis of CEA102, the uptake of the primary tumor (mean 1.10%ID/kg) was ten fold greater than that of the normal colon mucosa (mean 0.10%ID/kg). These results revealed that the application of MAb has great potential in radioimmunodetection as well as in antibody-directed therapy. PMID- 1506273 TI - Metabolism of tegafur in rat liver observed by in vivo 19F magnetic resonance spectroscopy and chromatography. AB - Metabolism of tegafur in the rat liver was observed by in-vivo 19F magnetic resonance spectroscopy (MRS). After MRS observation, tegafur and q-fluorouracil (5-FU) in the liver were determined by a chromatographic method for comparison with the results of 19F-MRS. Rats were divided into 3 groups: 1) CCl4-induced liver injury group, 2) uracil combined group, 3) control group. Catabolism to fluoro-beta-alanine was suppressed in both the liver injury group and the uracil combined group. Low peaks of 5-FU and fluoronucleotides could be found only in the uracil combined group. The result of 19F MRS observation of each group was in agreement with the result of determination of tegafur and 5-FU by chromatography. This showed that substances which could be observed by 19F-MRS were in proportion to all intracellular fluoro-containing substances. 19F-MRS can provide direct information on the metabolism of fluoropyimidines non-invasively and it might be a useful aid in choosing suitable chemotherapy for patients. PMID- 1506274 TI - Effects of antitumor agents on subcutaneous implants and hepatic metastases of colon carcinoma 26 in mice. AB - We investigated the responses of experimentally produced hepatic metastases of colon carcinoma 26 tumor and subcutaneously (SC) implanted colon carcinoma 26 tumor in mice to 17 clinically-used and one under-development antitumor agents using same dose regimen. In intravenous administrations on days 7 and 14, there were no significant differences in their responses to most of the tested agents. However, there were big differences in the responses to some of the agents. Nimustine more effectively prolonged the lifespan of SC implanted tumor-bearing mice than of mice bearing hepatic metastases. Mitomycin C was, however, considerably more effective on hepatic metastases than on SC implanted tumor. ME2303, a new fluorinated anthracycline derivative, showed a similar effect to doxorubicin on both tumors. However, administrations of ME2303 on days 7, 11 and 15 showed more marked antitumor effect only on hepatic metastases than administrations on days 7 and 14. Doxorubicin was less active against both tumors for administrations on days 7, 11 and 15 than for those on days 7 and 14. These results suggest the importance of the site of tumor growth for the action of some drugs. ME2303 may be active against hepatic metastases if it is administered by multiple injections. PMID- 1506275 TI - Cell-killing activity and kinetic analysis of a novel antitumor compound NC-190, a benzo[a]phenazine derivative. AB - A novel antitumor compound, N-beta-dimethylaminoethyl 9-carboxy-5-hydroxy-10 methoxybenzo[a]-phenazine-6-carboxamide sodium salt (NC-190), was evaluated for antitumor activity in vitro against cultured tumor cell lines, and the kinetics of cell killing was elucidated. NC-190 strongly inhibited the growth of all of 3 murine tumor cell lines, 7 human tumor cell lines and 2 normal cell lines. With continuous exposure, the 50% inhibition concentrations were in the range of 0.005 0.06 micrograms/ml, except for KATO-III (2.15 micrograms/ml). By colony-forming assay, concentrations of NC-190 giving 90% cell kill (IC90) at various exposure times were obtained with HeLa S3 cells. The plot of IC90-exposure time on a log log scale was linear for NC-190 with a slope of -1, which is typical for cell cycle phase-nonspecific agents. A 2 h treatment with NC-190 induced a rapid reduction in cell viability at doses of more than 3 micrograms/ml. At the dose where colony formation was completely inhibited, cell viability was persistently reduced to below 20% during the cell culture period. NC-190 caused a dose- and time-dependent reduction in DNA synthesis. The inhibitions of RNA and protein synthesis were less than that of DNA synthesis. Spectroscopic studies of NC-190 mixed with calf thymus DNA demonstrated that NC-190 was capable of interacting with DNA. However, DNA thermal denaturation studies suggested that intercalation of NC-190 was weak in comparison with those of classical intercalating drugs. PMID- 1506276 TI - Radiosensitization and hypoxic cell toxicity of NLA-1 and NLA-2, two new bioreductive compounds. AB - Two new bioreductive compounds, 9-[3-(2-nitro-1-imidazolyl)propylamino]acridine hydrochloride (NLA-1) and 9-[2-(2-nitro-1-imidazolyl)ethylamino]acridine hydrochloride (NLA-2), have been prepared. They feature an acridine ring to intercalate with DNA, a 2-nitroimidazole ring as the radiosensitizing moiety and an amino functionality for increased DNA-binding and hydrophilicity. Time and concentration dependent cytotoxicity as well as radiosensitization efficacy of the two compounds under hypoxic or aerobic conditions were determined in vitro using V-79 cells and an MTT colorimetric or clonogenic assay. The isosensitization point (ISP), defined as that drug concentration which results in the same survival decrement upon exposure of hypoxic or oxygenated cells to a given radiation dose, has been determined for both compounds at 7.5 Gy and the values are significantly lower than the ISPs of 5-[3-(2-nitro-1 imidazolyl)propyl]phenanthridinium bromide, 2-(2-nitro-1-imidazolyl)ethylamine or misonidazole (MISO). NLA-1 and NLA-2 are potent hypoxic cytotoxins and on a concentration basis, more potent than MISO as radiosensitizers in vitro. The sensitization enhancement ratios were significantly increased when 1 h drug preincubation under hypoxia at 37 degrees C was applied, before irradiation at room temperature. PMID- 1506277 TI - Ossification of the membranous portion of the squamous part of the occipital bone in man. AB - The squamous part of the occipital bone consists of 2 parts, supraoccipital and interparietal. The supraoccipital develops both in cartilage and membrane. At the upper margin the bone lying between the superior and highest nuchal lines known as the torus occipitalis transversus is ossified in membrane by a pair of centres. This part of the supraoccipital represents the original membranous part of the primitive occipital bone of lower animals where the interparietals form part of the parietals. This segment of bone is labelled as the intermediate segment which probably never separates from the cartilaginous supraoccipital. The interparietal bone lying above the highest nuchal lines develops in membrane by 2 pairs of centres, 1 pair for the lateral plate and the other for the medial plate. Each centre consists of 2 nuclei. Failure of fusion between these centres or their nuclei with each other and the supraoccipital may give rise to various anomalies in the interparietal region which are discussed. This is the true interparietal bone which has migrated from the parietals of lower animals during evolution to become part of the occipital bone in man. When it appears as an anomaly in the form of an independent separate bone, the suture between it and the supraoccipital lies at the level of highest nuchal lines. There is no pre interparietal bone.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1506278 TI - The vasa vasorum of the rabbit carotid artery. AB - The anatomy of the vasa vasorum of the carotid arteries was assessed by light and electron microscopy in a series of 25 New Zealand White male rabbits. The low viscosity acrylic resin, LR White, was used to cast the microvasculature. The carotid artery was found to have an endothelial monolayer placed directly upon a broad fenestrated internal elastic lamina. The media consisted of 12-18 laminae comprised of smooth muscle cells, elastin, collagen and ground substance. Vasa vasorum were confined to the adventitial layer, with no penetration into the media. They arose directly from the lumen of the carotid artery in addition to the arterial branching points. The potential role of the vasa vasorum in the aetiology of atherosclerotic plaques is discussed. PMID- 1506279 TI - The structure and development of the 'plana semilunata' of the labyrinth of the trout. AB - Five plana semilunata consisting of tall epithelial cells were found in the semicircular canal ampullae of the trout labyrinth. All these areas began to develop after hatching. Their cells were cuboid at fry stages and prismatic in juveniles and adults. Cell outlines were smooth, with no basal infoldings of the plasma membrane or apical microvilli. The cell nucleus occupied basal locations in juveniles but migrated centrally in adults. The most conspicuous organelle, the smooth endoplasmic reticulum, was continuous with a well-developed vacuolar system. These cells stored numerous glycogen granules. The ultrastructural features of the plana semilunata strongly suggest their involvement in endolymph secretion. PMID- 1506281 TI - Scanning electron microscopy of the rabbit gallbladder mucosal microvasculature. AB - The arrangement of the microvasculature of the rabbit gallbladder was studied by means of scanning electron microscopy (SEM) of vascular corrosion casts and parallel uncorroded samples, together with correlated light microscopy (LM) observations. The outer layers of the gallbladder wall possess a coarse capillary network supplied by long and straight vessels which also give off numerous smaller twigs for the mucosal layer. Thin richly branched and anastomosing capillaries originate from the mucosal twigs. The mucosal capillaries are arranged in structures having a bowl-like configuration with the convexity facing towards the serosal layer, and the concavity corresponding to the epithelial lacunae seen by SEM of uncorroded samples. These structures were polygonal or irregularly rounded, and limited by vessels arranged in folds. The vessels running in these folds were capillaries and/or venules. The vascular folds corresponded to the epithelial folds demonstrated by SEM and LM of uncorroded samples. PMID- 1506280 TI - A quantitative description of the epididymis and its microvasculature: an age related study in the rat. AB - The morphology of the epididymal duct and, in particular, the epididymal microvasculature was examined at the light microscope level in young sexually mature rats (3-5 months) and aged rats (18 months) to investigate the structural changes that may occur within the organ as a result of ageing, and which may predispose the organ to pathological changes. Quantitative data on the microvascular network of the epididymis (percentage of capillaries in the interstitial region, average area and surface density of the capillary lumen) were collected in 4 regions of the epididymis: the initial segment, caput, corpus and cauda. Epithelial cell height, epididymal lumen diameter, number of smooth muscle cells and percentage of smooth muscle surrounding the duct were also assessed within the same 4 regions. The data for both young and aged groups revealed a trend of decreasing capillary size from the initial segment of the epididymis to the cauda by 23%. Further, the percentage of capillaries within the interstitial region of the epididymis decreases dramatically (52%) in the same direction. The possible contribution of lymphatic capillaries to the data is discussed. The data revealed that none of the parameters assessed changed significantly up to 18 months of age. The quantitative data on the microvascular morphology of the epididymis presented in this study provide the basis for subsequent studies directed at the blood flow dynamics of the organ. PMID- 1506282 TI - A stereological analysis of kidney structure of honeyeater birds (Meliphagidae) inhabiting either arid or wet environments. AB - Stereology was used to quantify components within the kidney of honeyeater birds. Arid zone and wet zone inhabiting 'matched' body mass pairs of birds were examined. The kidney structure of the arid zone white-fronted honeyeater, Phylidonyris albifrons (16.9 g), was compared with that of the wet zone New Holland honeyeater, Phylidonyris novaehollandiae (21.9 g), and that of the arid zone spiny-cheeked honeyeater, Acanthogenys rufogularis (42.5 g), with that of the wet zone little wattlebird, Anthochaera lunulata (62.0 g). Both arid zone honeyeaters had a significantly higher (P less than 0.001) percentage of medulla in the kidneys, while the wet zone birds had a significantly higher (P less than 0.001) percentage of cortex. There were few differences between arid and wet zone honeyeaters in the percentage of nephron components in the cortex and medulla. Both arid zone bird species had a significantly larger volume of medulla, a feature characteristic of a high ability to conserve water by producing a concentrated urine. Both wet zone species had a higher volume of cortex but the difference was not significant. Few differences were found in the volumes and surface areas of tubules within the nephron. Differences that did occur were not always consistent with a high ability to conserve either ions or water more efficiently. The volume and surface area of brush border in the proximal tubule were significantly higher in the little wattlebird. This characteristic may lead to a greater capacity of its kidneys to absorb both water and ions. PMID- 1506283 TI - Oocyte numbers are reduced in developing mouse ovaries cultured in testis conditioned medium. AB - Reduced numbers of oocytes were present in fetal ovaries of 13 d post coitum (dpc) mice, cultured for 4 d in medium conditioned (-CM) for 2 d by 13 dpc testes, compared with ovaries maintained in standard unconditioned medium. This effect was abolished by heat-inactivation of the testis-CM. Electrophoretic analysis of conditioned media revealed differences between testis-CM and ovary CM. Ovarian differentiation was otherwise unaffected by the testis-CM and gonadal volume was not significantly reduced. Organisation of ovigerous cords proceeded, even though the full complement of oocytes was absent, and connective tissue septa developed normally between the small cords. The reduction in oocyte numbers occurred without any inhibition of mullerian duct development. Since others, using transgenic mice, have shown, that higher concentrations of antimullerian hormone are required to decrease oocyte numbers than are necessary for duct regression, our results suggest that an additional factor is involved in producing this modified effect. PMID- 1506284 TI - Principles and mechanisms of automatic rotation during terminal extension in the human knee joint. AB - The mechanisms solely responsible for automatic rotation during terminal extension were investigated by means of destruction experiments on knee joint structures. These are the posterior cruciate ligament (PCL), the anterior cruciate ligament (ACL) and the curvature of the medial femoral condyle. The first mechanism is based on the extraordinary obliquity of the constantly taut PCL guiding bundle, which produces torque in the final extension stage. The second mechanism depends on the fact that the ACL becomes 'too short' towards the final extension stage, which in turn is due to the shape of the articular surfaces. The third mechanism is caused by the deflection of the medial femoral condyle by the intercondylar eminence of the tibia. Each of the collateral ligaments can, in their own right, prevent excessive automatic rotation. On the one hand, the mechanism of the automatic rotation is reversed during initial flexion by the medial collateral ligament (this would be 'too short' in the case of nonreversal). On the other hand, it is reversed by the popliteus muscle. It is suggested that automatic rotation is not related to securing an amuscular stance (locking mechanism). PMID- 1506285 TI - The intraglandular submandibular ganglion of postnatal and adult rats. I. A light and electron microscope study. AB - The structure of the intraglandular submandibular ganglion is described in both postnatal and adult rats. The ganglion is localised mainly at the hilum where the majority of the cell bodies are observed. Ganglia are also present in the intralobular septa of both the submandibular and the sublingual glands. Often they are found along the main salivary ducts with the larger ganglia being encapsulated by connective tissue. On electron microscopy, the submandibular ganglion cells show the usual features of autonomic neurons. The cells contain a prominent round nucleus. Numerous short processes project from the soma together with a few long dendrites. The organelles are randomly distributed throughout the soma. Most of the synapses observed were on the short processes with occasional axosomatic synapses. Nonsynaptic desmosome-like contacts are a common feature among the ganglion cells. Especially noteworthy are contacts made by the dendrites which deeply invaginate the soma of an adjacent nerve cell. The ganglion cells of the postnatal and adult submandibular ganglia show minor differences. Ultrastructurally, the postnatal cells show signs of immaturity such as abundant free ribosomes, well developed Golgi complexes and disorganised rough endoplasmic reticulum. Mitotic satellite cells were observed associated with the postnatal ganglion cells. The study has confirmed that all the submandibular ganglion cells show a positive reaction for acetylcholinesterase. Enzyme activity is localised in the cisternae of rough endoplasmic reticulum, the Golgi complex, plasma membrane and nuclear envelope. PMID- 1506286 TI - An ultrastructural study of the cytoplasmic aspects of erythrocyte membranes by a quick-freezing and deep-etching method. AB - A novel method for preparing exposed cytoplasmic aspects of erythrocyte membranes is described which improves the resolution in direct electron microscope images. Normal human erythrocytes were briefly fixed with paraformaldehyde and pelleted. Glass coverslips were coated with 3-aminopropyl triethoxysilane and glutaraldehyde to make erythrocytes stick to them. A drop containing the erythrocyte pellets was sandwiched between 2 coverslips. The attached erythrocytes were split open mechanically and postfixed with glutaraldehyde. Some were treated with Triton X-100 or postfixed with osmium tetroxide. All specimens were quickly frozen in an isopentane-propane mixture, deeply etched and rotary shadowed with platinum and carbon. Filamentous structures were seen to form networks on the cytoplasmic sides of the erythrocyte membranes. Triton X-100 and osmium tetroxide fixation distorted the fine network structure. This quick freezing and deep-etching method will be useful in the analysis of the in situ ultrastructure of the cytoplasmic sides of erythrocyte membranes. PMID- 1506287 TI - Variations in the intertubercular sulcus of the humerus related to handedness. AB - Measurements of the maximum width and depth of the intertubercular sulcus (ITS) and the angles formed by the medial and lateral walls of the ITS with the plane of its floor were recorded in 200 adult human humeri, 100 each from the right and left sides. The ITS was more often wider and its medial wall formed a more acute angle with the plane of its floor in right-sided humeri. A supratubercular ridge on the humerus was present more frequently on the right than on the left. The presence of this ridge is probably more necessary on the right to prevent medial displacement of the long head of the biceps tendon from the ITS. The greater thrust exerted by the taut tendon of the long head of the biceps in the upper limb that is used preferentially probably induces structural differences in the ITS. PMID- 1506288 TI - The structure of the insertions of the tendons of biceps brachii, triceps and brachialis in elderly dissecting room cadavers. AB - The terminal portions of the tendon of brachialis, and the distal tendons of biceps brachii and triceps, were compared by routine histology. All tendons came from elderly dissecting room cadavers. There were pronounced quantitative differences between the 3 tendons in (1) the thickness of the attachment-zone fibrocartilage, (2) the thickness of cortical calcified tissue, and (3) the percentage of bone to marrow. There was significantly more uncalcified fibrocartilage at the attachment of biceps than at the other sites, reflecting greater range of movement of the tendon at this site. The thickness of cortical calcified tissue and the percentage of bone to marrow were significantly greater at the attachment of brachialis than either biceps or triceps. The large quantities of bone at the attachment of brachialis may be related more to the importance of the coronoid process in buttressing the elbow joint than to any special requirement for large amounts of calcified tissue at the tendon attachment. Near its attachment zone, the biceps tendon splits into superficial and deep laminae that are distinct from the macroscopic subdivision of this tendon. It is suggested that the lamination may facilitate the movements of pronation and supination. In support of this, the deep portion of the superficial lamina contained fibrocartilage where it rubbed against the attachment-zone of the deep lamina. In one body, the fibrocartilage of the biceps attachment-zone was subject to degenerative changes, including cell clumping and matrix fissuring. PMID- 1506289 TI - Activation and re-expression of surface antigen in microglia following an epidural application of kainic acid in the rat brain. AB - Following an epidural application of kainic acid over the sensorimotor cortex in rats, the ipsilateral hippocampus and the ventrobasal nuclear complex of the thalamus showed extensive neural degeneration. The neuronal death, either as a result of direct neurotoxic destruction or wallerian and retrograde degeneration, elicited a dramatic expression of immunoreactivity on numerous cells bearing the external morphology of microglia. Thus, with the monoclonal antibody OX-42, many amoeboid immunoreactive cells bearing stout processes were observed in the above mentioned lesioned sites. The present electron microscopic immunocytochemical study confirmed that these OX-42 positive cells were activated microglia characterised by an abundant cytoplasm containing a variable number of lysosomes and phagosomes. The surfaces of these activated microglial cells were thrown into pseudopodial processes engaged in the phagocytosis of cellular debris. Immunoreactivity was also observed in these cells with the monoclonal antibodies OX-18 and OX-6, although in the latter the immunoreactive cells were fewer and less intensely stained. With OX-42, the corresponding areas on the contralateral side showed some widely scattered typical microglial cells bearing extremely fine processes. They were not stained with either OX-18 or OX-6. It was concluded from this study that neural degeneration induced the expression of CR3 receptors (marked by OX-42) and MHC encoded antigens (marked by OX-18 and OX-6) in microglia. The elevation of the former antigen was related to their active phagocytic activity. The latter, on the other hand, would facilitate the capability of interaction between the activated microglia and T lymphocytes in a possible immune response. PMID- 1506290 TI - Magnetic resonance imaging of semicircular canals. AB - The present paper reports the results of the first investigation of the semicircular canals in a living, small animal by means of high spatial resolution magnetic resonance imaging. This procedure is noninvasive and allows identification of the endolymphatic and perilymphatic spaces yielding a morphology quite consistent with direct anatomical examination. PMID- 1506291 TI - In memoriam Professor Fritz Jacoby. PMID- 1506292 TI - Effects of alternative lamb production systems, maternal line, and culling strategy on flock age structure. AB - The 5-yr attrition of 1/4 (n = 411) or 1/2 (n = 403) Finnsheep (Finn) ewes exposed to terminal sire breeds in either an accelerated or semi-intensive annual lambing system was recorded to test the effects of system and percentage Finn on flock age structure at equilibrium. Ewes were culled for discernible ailments and failure to lamb after two consecutive non-spring exposures in yr 3, 4, or 5 only. Additionally, four progressively more intensive culling strategies for nonconception were practiced in retrospect. Flock productivity (kilograms of lamb weaned per ewe maintained per year) at age structure equilibrium was estimated for all culling strategies. The majority of all systems (cull strategy x lambing system x percentage Finn combination) were composed of ewes less than or equal to 3 yr old. Replacement requirements ranged from 24 to 38% in the accelerated system and 22 to 26% in the annual system. Quarter-Finns yielded greater replacement needs and shorter productive lives in accelerated lambing but fewer replacement requirements and longer productive lives than 1/2 Finns in annual lambing. Replacement requirements greatly increased with culling intensity in accelerated lambing (up to 54% above original levels) but only slightly in annual lambing (up to 8% above original levels). Mean (reproductive) lifetime estimated from fitted Weibull survival curves ranged from 3.1 to 5.1 yr in accelerated lambing and 4.5 to 5.4 yr in annual lambing. Increased culling for non-lambing decreased productivity at flock age structure equilibrium in accelerated lambing but did not change productivity in annual lambing. Repeatability of ewe effects on conception was generally low. Overall, system, percentage Finn, and culling strategy interact to influence system productivity through flock age structure. Intensive culling for non-lambing and replacement with ewe lambs of equal genetic merit should not be practiced in accelerated lambing systems. PMID- 1506293 TI - Influence of calving season and stocking rate on birth weight and weaning weight of Simmental-sired calves from Brahman-Hereford F1 dams. AB - Braham-Hereford F1 dams have been used to evaluate the influence of grazing pressure on forage attributes and animal performance at the Texas A&M University Agricultural Research Center at Overton. Data for this study were compiled from 1,909 records of Simmental-sired calves born to Braham-Hereford F1 cows from 1975 to 1990. Birth weight and weaning weight were analyzed independently to estimate the influence of year, season of birth, dam age, weaning age, and sex of calf. The effect of stocking rate as represented by levels of forage availability on weaning weights and subsequent birth weights was measured. Within the fall and winter calving seasons, lactating dams grazing at a high stocking rate produced calves with the lowest subsequent birth weights. Lactating dams assigned to creep fed treatments had calves with the heaviest subsequent birth weights. Although dams that were less than 3.5 yr of age had calves with the lightest birth weights, there was no apparent decline in birth weight of calves from dams 12 to 17 yr old. Year, sex of calf, age of dam, stocking rate, season of birth, age at weaning, and birth weight were significant factors affecting weaning weight (P less than .01). Fall-born calves grazing cool-season annual pastures were heavier at weaning (267.6 kg) than either winter- (252.0 kg) or spring-born calves (240.9 kg). A stocking rate x season-of-birth interaction was observed for birth weight and weaning weight (P less than .05). Differences in weaning weight from low- vs high-stocked pastures were greater for fall-born calves (61.6 kg) than for winter born calves (48.7).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1506294 TI - Prediction of carcass characteristics by real-time ultrasound in barrows and gilts slaughtered at three weights. AB - The carcass characteristics of 27 market barrows and 27 market gilts were evaluated at various times (n = 8) with real-time ultrasound (Aloka 210 DX) from approximately 20 kg until slaughter at three end points. The pigs were randomly assigned to slaughter weight groups of 91, 104.5, and 118 kg at weaning time. Correlations were determined over slaughter weight group and sex, and the accuracies of ultrasound measurements were also evaluated. The regressions of ultrasound 10th-rib fat and ultrasound longissimus muscle area on live weight were also developed. Correlations between actual and ultrasound-measured last-rib fat, 10th-rib fat, and longissimus muscle area were high (r = .91, .63, and .53, respectively; P less than .01). The accuracy of ultrasound longissimus muscle area prediction was lower for 118-kg pigs than for the two lighter groups, whereas the accuracy for prediction of last-rib fat was lower for 91-kg pigs than for the two heavier groups, as indicated by higher absolute differences (P less than .05). Last-rib fat and longissimus muscle area tended to be overestimated and 10th-rib fat tended to be underestimated by real-time ultrasound. Prediction of last-rib fat by ultrasound was more accurate for gilts than for barrows, as indicated by a lower absolute difference (P less than .05). PMID- 1506295 TI - Correlated changes in reproductive components accompanying 10 generations of selection for improved sow productivity index. AB - Reproductive components were compared between a line of sows selected (S) for improved sow productivity index (SPI = 6.5 x number born alive + adjusted 21-d litter weight) and sows from an unselected control (C) line. Generation 9 and 10, second-parity, Landrace sows were chosen from both the S (n = 35) and C (n = 33) line. Sows were slaughtered at a commercial slaughter plant at approximately 75 d of gestation and their reproductive tracts were recovered. Reproductive tracts were evaluated for uterine weight (UTWT), uterine horn length (UTLN), ovulation rate (OR), number of fully formed fetuses (NF), number of mummified fetuses (NM), percentage of fetal survival (FS = NF/OR), fetal space (FSPACE = UTLN/[NF + NM]), and fetal position, sex, and weight. Select-line sows had greater NF (P less than .10) and higher FS (P less than .10) than C-line sows. Select-line sows had longer (P less than .05), and heavier (P less than .01) uteri than C-line sows. However, uterine length adjusted for NF was not different between the two lines. Uterine weight adjusted for NF was greater in S-line sows (P less than .05). Select-line sows had greater total fetal weight (TFWT) (P less than .05) than did C-line sows. Female fetuses positioned between two male fetuses were lighter in weight than all other female fetuses (P less than .01). Male fetuses positioned between two female fetuses did not differ in weight from all other male fetuses.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1506296 TI - Economic evaluation of heterosis and culling policies for lifetime productivity in Hereford, Angus, shorthorn, and crossbred cows. AB - Experimental lifetime performance data obtained from 156 straightbred Hereford, Angus, and Shorthorn and 172 first-cross heifers were used to estimate heterosis for economic efficiency in a 100-cow herd at age equilibrium under three culling policies and at terminal ages from 6 to 12 yr. All nonpregnant heifers and cows greater than 9 yr of age were culled. The culling policy for removal of nonpregnant cows from second parity through 9 yr of age were 1) no culling, 2) after two consecutive years (actual), and 3) all (imposed). Efficiency was calculated as input cost per unit of output value. A 10-yr average was used for costs of replacement heifers, cow units, and the ratio of calf:cull cow prices (PR), plus higher and lower PR. Input included costs for both cow units and purchased replacements. Output value included both weaned calves and cull cows. Optimum terminal age was mainly a function of PR: 9 yr for average and high PR, but 6 through 9 yr when PR was low, regardless of culling policy or breed groups. Efficiency differences among culling policies were small for high or average PR, but more culling for infertility was beneficial when PR was low. Estimated reductions in unit costs of output value under any culling policy or terminal age were approximately 6% from crossbred cows plus another 6% from crossbred calves, or a total of 12% from specific three-breed crossing of these British breeds. Cost reductions would be somewhat less for rotation crossbreeding but greater for mating smaller crossbred cows with sires of superior growth-carcass breeds. PMID- 1506297 TI - Effect of culling on selection response using phenotypic selection or best linear unbiased prediction of breeding values in small, closed herds of swine. AB - Records from 7,200 separate closed herds with either 12 or 25 sows that were mated to either four or eight boars per year were simulated by computer. Effects of selection method, herd size, and contemporary group variability on average genetic change, genetic variance, and inbreeding over 10 yr of selection were analyzed for traits with heritabilities of .1, .3, and .6. Selection of replacement animals was on individual phenotype or BLUP of breeding value using a reduced animal model. For both of these selection methods, two culling schemes were imposed: 1) based only on involuntary culling because of losses due to conception rate and age and 2) when an available replacement animal was projected to be superior to an existing breeding animal in the herd in addition to the involuntary culling. The contemporary group standard deviation was set at either .1 or .5 of a phenotypic standard deviation. Selection with BLUP gave 72, 36, and 12% more genetic improvement for heritabilities of .1, .3, and .6, respectively, than selection on individual phenotype after 10 yr. However, inbreeding increased 20 to 52% more rapidly and there was a decrease in genetic variance. Culling based on Scheme 2 increased genetic improvement over Scheme 1 by about 75% with coincident increases in inbreeding level and decreases in genetic variance. The largest changes in inbreeding and genetic variance were associated with culling on BLUP. Culling when a superior animal was available with individual phenotype had little effect on inbreeding and genetic variance. Use of four boars rather than eight boars and 25 rather than 12 sows per herd increased genetic response. Use of four boars also increased inbreeding and decreased genetic variance. Genetic variance was higher in herds with 25 sows, but the size of the sow herd had little effect on inbreeding. Contemporary group variation influenced only the genetic response of individual phenotypic selection with culling. PMID- 1506298 TI - An embryo transfer study of reciprocal cross differences in growth and carcass traits of Duroc and Landrace pigs. AB - Reciprocal cross differences have been reported for growth rate and carcass traits in F1 pigs with the Duroc (D) as a parent breed. Such differences are synonymous with maternal effects if effects of sex linkage and genomic imprinting are negligible. In the present study, transfer of embryos (ET) to paternal breed recipients partitioned effects occurring at or before fertilization from postfertilization effects for growth and carcass traits in F1 D-Landrace (L) pigs. Fifteen boars sired 115 F1 litters, 49 produced by ET. Growth rate of 349 barrows and 361 gilts and carcass measurements on 256 barrows and 159 gilts were analyzed assuming mixed linear models with animal and litter as random effects. Contrasts among genotype (D x L, L x D)- treatment (ET, non-ET) means were tested. Reciprocal cross differences were not detected for growth rate or for carcass weight, length, average backfat thickness, estimated carcass lean, or lean per day of age. Reciprocal cross differences for 10th rib backfat thickness (BF) and longissimus muscle area (LMA) were detected only in barrows. The sexual dichotomy for reciprocal cross differences followed expectations for a Y-linked gene(s), consistent with the fact that reciprocal D-L crossbred barrows exhibited a paternal effect, with responses more like the sire breed than the dam breed. Barrows that were non-ET from D sires and L dams had 3.9 cm2 larger LMA and 5.8 mm less BF than barrows from L sires and D dams (P less than .001). Barrows from ET sired by D boars had 3.8 cm2 larger LMA than did barrows from ET sired by L boars (P less than .001), although no difference was detected for BF. Barrows sired by D boars reared in a D postfertilization environment (ET) had 6.2 cm2 greater LMA and 4.1 mm less BF (P less than .05) than barrows sired by L boars gestated and reared by D dams (non-ET). Barrows sired by D boars reared by L dams (non-ET) had 1.5 cm2 greater LMA and 2.3 mm less BF (P greater than .10) than barrows sired by L boars reared by L dams (ET). In conclusion, reciprocal cross differences detected for BF and LMA in barrows were established before or at fertilization and seemed to be Y-linked. PMID- 1506299 TI - Sire x herd interactions for weaning weight in beef cattle. AB - Weaning weight records of 44,357 Australian Angus calves produced by 1,020 sires in 90 herds were used to evaluate the importance of sire x herd interactions. Models fitted fixed effects of contemporary group (herd-year-date of weighing subclass), sex, calf age, and dam age and random effects of sire or of sire and sire x herd interaction using REML. Effects of standardizing the data, including sire relationships and including dam maternal breeding values (MBV) as a covariate were also investigated. Sire x herd interactions were found (P less than .05) in all cases and, in the most complete model, accounted for 3.3% of phenotypic variance. Across-herd heritabilities ranged from .19 to .28. Differential nonrandom mating among herds seemed to occur in the data. Significant sire x herd effects were observed for dam MBV, and adjustment for dam MBV yielded the smallest estimates of interaction variance and across-herd heritability. If sire x herd interactions were due only to genotype x environment interaction, within-herd heritabilities would range from .33 to .49. These estimates are larger than previously reported estimates. Thus, unreported environmental effects common to progeny of individual sires may also be involved in the observed interaction but could not be disentangled from true genotype x environment interaction effects using these data. Results of these analyses suggest that some accommodation of sire x herd interaction effects on weaning weight may be needed in beef cattle genetic evaluations, but a compelling case for development of herd-specific breeding value prediction cannot be made. PMID- 1506300 TI - Effects of breed and retained heterosis on milk yield and 200-day weight in advanced generations of composite populations of beef cattle. AB - Retained heterosis in F2 cows nursing F3 progeny was evaluated in 3-, 4-, and greater than or equal to 5-yr-old cows. Traits evaluated included milk yield at three stages of lactation and 200-d weight of progeny. Breed effects were evaluated in the nine parental breeds (Red Poll [R], Hereford [H], Angus [A], Limousin [L], Braunvieh [B], Pinzgauer [P], Gelbvieh [G], Simmental [S], and Charolais [C]) that contributed to the three composite populations (MARC I = 1/4 B, 1/4 C, 1/4 L, 1/8 H, 1/8 A; MARC II = 1/4 G, 1/4 S, 1/4 H, 1/4 A; and MARC III = 1/4 R, 1/4 P, 1/4 H, 1/4 A). Breed effects were significant for 12-h milk yield, estimated 200-d milk yield, and 200-d weight of progeny. Herefords were lowest (P less than .05) for 12-h milk yield and estimated 200-d milk yield, and Braunvieh produced significantly more milk than all breed groups except Pinzgauer and Simmental, for which the difference approached significance. The correlation among breed group means (nine parental breeds and three composites) for 12-h milk yield with 200-d weight of progeny was .91. When 200-d weight was adjusted to a common estimated 200-d milk yield, Hereford, Angus, Red Poll, and Limousin did not differ (P greater than .05); all were significantly lighter than Braunvieh, Pinzgauer, Gelbvieh, Simmental, and Charolais, which did not differ (P greater than .05) from each other.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1506301 TI - Genetic analyses of growth, real-time ultrasound, carcass, and pork quality traits in Duroc and Landrace pigs: I. Breed effects. AB - Knowledge of breed effects on carcass and pork quality traits is required to develop commercial crossbreeding programs that emphasize product quality. A 2 x 2 diallel mating system involving Landrace and Duroc pigs was used to estimate individual heterosis, direct breed effects and reciprocal cross differences for post-weaning growth, real-time ultrasound, carcass, and pork quality traits. Data from 5,649 pigs and 960 carcasses representing 65 and 49 sires, respectively, were analyzed assuming animal models. Duroc-sired pigs had 2.1 cm shorter carcasses with 7.3 mm less 10th rib backfat (BF), 4.4 cm2 larger longissimus muscle area (LMA), yielded 2.1 kg more estimated fat standardized lean (FSL), gained 16.5 g more estimated lean per day of age (LDOA), and had 1.0% less water (PWAT) and 1.9% more intramuscular fat (IMF) in the longissimus muscle than did Landrace-sired pigs (P less than .01), adjusted to an off-farm live weight of 111 kg. Reciprocal cross differences were detected for BF, LMA, FSL, LDOA and for subjective marbling, firmness, and muscling scores (P less than .01). Durocsired F1 barrows had 6.3 mm less BF and 5.9 cm2 larger LMA, yielded 3.2 kg more FSL, gained 22.3 g more LDOA, and had less marbling in the longissimus muscle and heavier ham muscling than reciprocal cross barrows. Heterosis estimates (P less than .05) were 27.6 g/d (3.2%) for ADG, -5.8 d (-3.6%) for off-test age, 2.7 cm (3.4%) for carcass length, 1.5 kg (7.2%) for FSL, 14.7 g (5.7%) for LDOA, -.07 ( 3.6%) for muscle color, -.5% (-13.2%) for IMF, and .3% (.3%) for PWAT. Breed effects were not detected (P greater than .10) for muscle pH, cooking loss, shear value, and water-holding capacity or for eating quality traits. Reciprocal cross differences suggest an advantage in using the Duroc as a terminal sire, but improved carcass composition and higher intramuscular fat did not seem to affect eating quality traits. PMID- 1506302 TI - Genetic analyses of growth, real-time ultrasound, carcass, and pork quality traits in Duroc and Landrace pigs: II. Heritabilities and correlations. AB - Knowledge of the genetic control of pork quality traits and relationships among pork quality, growth, and carcass characteristics is required for American swine populations. Data from a 2 x 2 diallel mating system involving Landrace and Duroc pigs were used to estimate heritabilities and genetic correlations among growth (ADG), real-time ultrasonic (US) measures of backfat thickness (BF) and longissimus muscle area (LMA), carcass characteristics, and various pork quality traits. Data were collected from 5,649 pigs, 960 carcasses, and 792 loin chops representing 65, 49, and 49 sires, respectively. Genetic parameters were estimated by REML assuming animal models. Heritability estimates were moderate to high for ADG, USBF, USLMA, carcass BF, and LMA, percentage of LM lipid (IMF), pork tenderness, and overall acceptability. Estimates were low to moderate for percentage of cooking loss, pH, shear force, percentage of LM water, water holding capacity (WHC), pork flavor, and juiciness. Genetic correlations between US and carcass measures of BF and LMA indicate that selection based on US data will result in effective improvement in carcass characteristics. Selection for increased LMA and(or) decreased BF using US is, however, expected to result in decreased IMF and WHC, increased percentage of LM water and shear value, and in decreased juiciness, tenderness, and pork flavor. Average daily gain was favorably correlated with IMF and unfavorably correlated with shear force. Selection for increased ADG is expected to improve WHC but to decrease the percentage of LM water, with an associated decrease in juiciness. The results of this study suggest the feasibility of including meat quality in selection objectives to improve product quality. Favorable genetic correlations between IMF and eating quality traits suggest the possible merit of including IMF in the selection objective to improve, or restrict change in, pork eating quality. PMID- 1506303 TI - Heterosis for lifetime production in Hereford, Angus, shorthorn, and crossbred cows. AB - The effects of maternal heterosis and maternal and grandmaternal breed effects on cumulative lifetime number and weight of calves weaned per cow entering the breeding herd were evaluated for 172 reciprocal crossbred and 156 straightbred cows of the Hereford, Angus, and Shorthorn breeds. Cows born in 1960 and 1961 were developed and mated to calve first at 3 yr of age and those born in 1962 and 1963 at 2 yr of age. Performance under actual culling of cows nonpregnant in two consecutive years and imposed culling of any nonpregnant cows were analyzed. Reproductive rates and weaning weight per calf and per cow exposed increased (P less than .05) as cows advanced from 2 through 5 yr of age, peaked at ages 5 through 9 yr, and decreased from 9 through 12 yr. Effects of heterosis did not interact (P greater than .05) with age at first calving management. During the 12 yr span in the 2-yr-old first-calving management system, crossbred cows produced nearly one more calf than straightbred cows under the actual culling policy (.97 calves, P less than .10) and .82 more calves (P less than .10) if all nonpregnant cows were culled. Corresponding cumulative calf weight weaned was 272 kg (P less than .01), or 25% more, and 232 kg (P less than .01), or 30% more, for crossbred cows than for straightbred cows. The 12-yr cumulative calf weight weaned by straightbred Angus cows exceeded that of Shorthorn cows (P less than .05) and tended to be greater than that of Hereford cows. PMID- 1506304 TI - Estimates of subprimal yields from beef carcasses as affected by USDA grades, subcutaneous fat trim level, and carcass sex class and type. AB - One hundred beef carcasses were selected to represent the mix of cattle slaughtered across the United States. Selection criteria included breed type (60% British/continental European, 20% Bos indicus, and 20% dairy carcasses), sex class (beef and Bos indicus: 67% steers, 33% heifers; dairy: 100% steers), USDA quality grade (4% Prime, 53% Choice, and 43% Select), USDA yield grade (10% YG 1, 43% YG 2, 40% YG 3, and 7% YG 4), and carcass weight (steers: 272.2 to 385.6 kg, heifers: 226.8 to 340.2 kg). One side of each carcass was fabricated into boneless subprimals and minor cuts following Institutional Meat Purchase Specifications. After fabrication, subprimals were trimmed progressively of fat in .64-cm increments beginning with a maximum of 2.54 cm and ending with .64 cm. Linear regression models were developed for each individual cut, including fabrication byproduct items (bone, fat trim) to estimate the percentage yield of those cuts reported by USDA Market News. Strip loin, top sirloin butt, and gooseneck rounds from heifers tended to have a higher percentage yield at the same USDA yield grade than the same cuts from steers, possibly resulting from increased fat deposition on heifers. Percentage of fat trimmed from dairy steers was 2 to 3% lower than that from other sex-class/carcass types; however, due to increased percentage of bone and less muscle, dairy steers were lower-yielding. Fat trimmed from carcasses ranged from 7.9 to 15.6% as the maximum trim level decreased from 2.54 to .64 cm. PMID- 1506305 TI - Beef carcass composition of slaughter cattle differing in frame size, muscle score, and external fatness. AB - Commercial slaughter steers (n = 329) and heifers (n = 335) were selected to vary in slaughter frame size and muscle thickness score, as well as carcass adjusted 12th-rib fat thickness. After collection of USDA carcass grade data, one side of each carcass was fabricated into boneless primals, subprimals, and minor tissue components. Cuts were trimmed to 2.54, 1.27, and .64 cm of external fat, except for the knuckle, tri-tip, and tenderloin, which were trimmed of all fat. Forced four-variable regression equations were used to predict the percentage (chilled carcass weight basis) yield of boneless subprimals at the three fat trim levels as influenced by sex class, frame size, muscle score, and adjusted 12th-rib fat thickness. Independent variables that had the most influence on percentage yield of primals and boneless subprimals were adjusted 12th-rib fat thickness and sex class. Within the same phenotypic group, percentage of trimmable fat increased by 2.32% as 12th-rib fat thickness increased by .75 cm. Estimated percentage yield of the major subprimals from the loin and round tended to be higher or relatively equal for heifer carcasses at all trim levels compared with those subprimals from steer carcasses. Holding frame size, sex class, and fat thickness constant, there was a higher percentage yield of chuck roll, rib eye roll, and strip loin for carcasses from thick-muscled cattle than for those from average- and thin-muscled cattle. Frame size had little effect on percentage yield of boneless subprimals. PMID- 1506306 TI - Meat composition and palatability of Holstein and beef steers as influenced by forage type and protein source. AB - This experiment determined meat composition and palatability changes resulting from feeding Holstein (HOL) and crossbred beef (XB) steers diets containing corn silage (CS) or alfalfa haylage (AH) (forage type) and soybean meal (SM) or fish meal (FM) (protein source). Fifty-nine steers (30 HOL and 29 XB) were randomly assigned to diet combinations for a 2 x 2 x 2 (breed x forage x protein) factorial arrangement. Steers were fed to a fat-constant end point (fat depth over the longissimus muscle measured by ultrasound: 1.0 cm XB, .6 cm HOL). Proximate and fatty acid analysis and sensory evaluation were conducted on a rib eye roast and steaks, respectively, removed from the left side of each carcass at ribs 9 to 12. Proximate analysis of the longissimus muscle showed no significant difference (P greater than .05) in moisture, protein, or fat content due to breed, forage, or protein treatment. Forage type had no significant effect (P greater than .05) on amount of individual fatty acids found in longissimus muscle. However, total polyunsaturated fatty acids were higher (P greater than .05) for AH than for CS-fed animals. Longissimus muscle from steers fed FM had higher palmitoleic and lower stearic acid contents (both P less than .05) than longissimus muscle from animals fed SM. Muscle from HOL had higher palmitoleic and lower stearic acid contents than that from XB steers (both P less than .05). There was no significant interaction (P greater than .05) of breed with either diet treatment for individual fatty acid contents.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1506307 TI - Preparation of muscle samples for comparative electron microscopy. AB - The interpretation of muscle structure by scanning electron microscopy (SEM) has not been consistent among various studies. Consequently, the literature is confusing with respect to the identity of T-tubules, transverse ridges, Z-disks, and intermyofibrillar connections. The objective of this research was to evaluate the effects of different methods of sample preparation and imaging on ultrastructural details of previously identified transverse structures and intermyofibrillar connections and to verify or disprove the commonality of these structures under different viewing conditions. Scanning electron microscopy coupled with a cold stage, SEM at room temperature, and transmission electron microscopy (TEM) of thin sections were most appropriate for exposing detail of inter- and intracellular structures and for measuring sarcomere length and spacing of intermyofibrillar connections. Scanning electron microscopy of samples mounted on a cold stage, fractured, and sublimed provided excellent images of meat and muscle ultrastructure and may be used in correlative microscopy. Sarcomere length and spacing between intermyofibrillar connections were similar among most specimen preparation techniques and were affected similarly by heat treatments. Results indicate that the regularly spaced transverse structures viewed by conventional SEM and the intermyofibrillar connections viewed by low temperature SEM are Z-disks. PMID- 1506308 TI - Effect of dietary fat and cholesterol level on growing pigs selected for three generations for high or low serum cholesterol at age 56 days. AB - Thirty-six female pigs selected for three generations for high (HS, n = 18) and low (LS, n = 18) serum cholesterol at 56 d of age were used to test the hypothesis that the two populations would respond differently to a high-fat, high cholesterol diet (HD) and a low-fat, low-cholesterol diet (LD). The animals were four-way crosses (Chester White x Landrace x Large White x Yorkshire). All pigs were fed a standard corn-soybean meal starter diet from weaning (at 4 wk) to 8 wk of age and a grower diet from 8 to 12 wk of age. Initial serum total cholesterol concentration at 12 wk of age was higher (P less than .05) in HS than in LS pigs (94.6 vs 76.9 mg/dL, respectively). The effect of genetic background persisted throughout the 13-wk experiment (25 wk of age); there was no interaction between diet and genetic background in serum total cholesterol (final concentrations were 114.3 mg/dL in HS-HD; 107.0 mg/dL in HS-LD; 105.9 mg/dL in LS-HD; and 89.7 mg/dL LS-LD). Trends over time revealed significant effects of diet (P less than .01) and genetic background (P less than .01) on serum total cholesterol. There was no effect of genetic background on high-density lipoprotein-cholesterol concentration; high-density lipoprotein-cholesterol as a percentage of serum total cholesterol was similar for all groups: 43% for HS-HD, 48% for HS-LD, 42% for LS-HD, and 45% for LS-LD.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1506309 TI - Efficacy of dietary D-alpha-tocopherol and DL-alpha-tocopheryl acetate for weanling pigs. AB - A 2 x 3 factorial experiment in a randomized complete block design was conducted using a total of 180 weanling pigs in five replicates. The study evaluated the efficacy of two dietary vitamin E sources (D-alpha-tocopherol, DL-alpha tocopheryl acetate) added at three dietary levels (16, 48, 96 IU/kg) during a 35 d postweaning trial. Pigs within each treatment were fed two similarly fortified vitamin E diets in sequence; the first contained 40% milk products and was fed to 14 d, and the second contained 20% milk product and 5% fat and was provided from 15 to 35 d postweaning. Five pigs per pen per replicate were bled weekly for serum analysis of alpha-tocopherol, Se, cholesterol, triglyceride, and glutathione peroxidase (GSH-Px) activity. At the end of the trial, one pig per pen was randomly selected and killed with liver, loin, lung, and heart excised and frozen for tocopherol analysis. Postweaning gains, feed intakes, and efficiencies were similar between the two vitamin E sources and at the various dietary levels. Serum tocopherol concentrations were consistently higher when D alpha-tocopherol was provided. Vitamin E sources and levels had no effect nor did they influence weekly serum Se, cholesterol, or triglyceride concentrations or GSH-Px activity. A serum and tissue interaction (P less than .05) response occurred between dietary vitamin E source x level with alpha-tocopherol concentrations increasing linearly (P less than .01) as dietary vitamin E level increased, but at a higher rate when D-alpha-tocopherol than when DL-alpha tocopheryl acetate as fed.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1506310 TI - Digestible tryptophan requirements of starting, growing, and finishing pigs. AB - Seven hundred eight crossbred pigs were used in growth and digestion trials to determine the digestible tryptophan (Trp) requirement of starting (6 to 16 kg), growing (22 to 50 kg), and finishing (55 to 97 kg) pigs. Each growth trial evaluated a corn-fish meal-corn gluten meal basal diet, the basal diet with five incremental additions of L-Trp, and a control corn-soybean meal diet. The tryptophan content of the six incremental diets ranged from .13 to .255% for starting pigs, .08 to .18% for growing pigs, and .063 to .163% for finishing pigs. Lysine contents of basal diets were 1.38, .90, and .72% for starting, growing, and finishing diets, respectively. In all trials, ADG, ADFI, and gain/feed increased (P less than .001) linearly and quadratically as dietary Trp increased. Broken-line regression analyses determined the total dietary Trp requirements needed to optimize performance to be .19, .13, and .09% (as-fed basis) for starting, growing, and finishing pigs, respectively. These concentrations equated to Trp intakes of .96, 2.18, and 2.88 g/d. A digestion trial using growing pigs (29 kg initially) determined the apparent ileal digestibility of Trp in the basal starting and growing diets to be 72 and 70%, respectively; a similar trial with finishing pigs (55 kg initially) found 59% Trp digestibility for the basal finishing diet. Mean digestibility of L-Trp was 97%. Based on these values and the total Trp requirements given above, the digestible Trp requirements are .15, .10, and .06% for starting, growing, and finishing pigs, respectively. PMID- 1506311 TI - Effect of consuming fungus-infected and fungus-free tall fescue and ergotamine tartrate on selected physiological variables of cattle in environmentally controlled conditions. AB - Two experiments were conducted to determine the physiological responses of consuming a fungus-free (FF) or fungus-infected (INF) tall fescue diet (Exp. 1) or the FF diet plus ergotamine tartrate at 30 ppm (FF/ET, Exp. 2) in a thermoneutral (21 degrees C) or heat-stressed environment (32 degrees C, dry bulb; 10 degrees C dew point). Treatment periods lasted 28 d after a 10-d adaptation period. Experiment 1 was replicated three times, and Exp. 2 was replicated twice, with eight Holstein steers in each replicate (mean BW = 185 kg). Feed intake (FI), rectal temperature (RT), and respiration rate (RR) were recorded daily, and heart rate (HR) and infrared temperatures at the ear canal (ECT), ear tip (ETT), pastern (PT), coronary band (CBT), and tail tip (TTT) were recorded weekly. Consumption of INF and FF/ET compared with FF diets decreased (P less than .10) FI, HR, ECT, PT, CBT, and TTT and elevated (P less than .10) RT and RR by 2.8, 2.77 kg/d; 17, 23 beats/min; .8, 1.1 degrees C; .9, 1.1 degrees C; .8, .9 degrees C; 1.1, 2.6 degrees C; .3, .5 degrees C; and 8, 8 breaths/min; respectively. Ear-tip temperature was reduced (P less than .10) 1.6 degrees C by consumption of INF but not by consumption of FF/ET. Reduction of peripheral temperatures is indicative of reduced blood flow to peripheral areas as a result of vasoconstriction.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1506312 TI - Effect of dietary cysteine supplements on canola meal toxicity and altered hepatic glutathione metabolism in the rat. AB - Experiments were conducted to determine the effects of feeding canola meal (Brassica campestris and Brassica napus) on the rat hepatic glutathione detoxification system and whether dietary cysteine supplements might modify such effects. Rats were fed test diets for 14 d. Body weight change, feed consumption, hepatic glutathione concentration, and hepatic glutathione-S-transferase (GSH-S T) activities were determined. Weight gain was decreased when canola meal was fed, whereas hepatic glutathione concentrations increased, as did hepatic GSH-S-T activity. All effects correlated with total glucosinolate concentration in the canola meal. Dietary cysteine supplements, however, did not influence the growth reduction and increased hepatic glutathione concentrations caused by feeding canola meal. Supplemental cysteine prevented the elevation in hepatic GSH-S-T activity. The elevation in hepatic glutathione concentration caused by canola meals was not an overcompensation caused by an initial depletion and therefore reflected a general hepatotoxicity. Feeding supplemental cysteine increased hepatic glutathione levels at early time intervals and delayed the induction of GSH-S-T caused by canola meal toxicity. There was no beneficial effect of supplemental dietary cysteine in overcoming the toxicity of high levels of canola meal, but supplemental cysteine did modify the canola meal-induced changes in hepatic glutathione metabolism. PMID- 1506314 TI - Alteration of energy metabolism of calves fed below maintenance during 6 to 14 days of age. AB - A study was conducted with seven groups of five to six Holstein-Friesian male calves to evaluate the effect of feeding level during 6 to 14 d of age on energy metabolism of unadapted young calves. Calves were transported at 2 to 3 d of age to their new environment. At 6 d of age measurements of heat production (HP) and ME intake started and continued over a period of 8 d. Calves were fed below (four groups) or near (three groups) the maintenance requirement (19 or 30 g of milk replacer powder.kg-.75.d-1). In contrast to ME intake, HP decreased throughout the experimental period. This decrease was larger at the low than at the high feeding level (3.1 vs .9 kcal.kg-.75.d-2; P less than .001). The relationship between HP and ME intake was estimated as HP = 91 + .318 x ME intake (kilocalories.kilogram-.75.day-1). The decrease in HP, together with the constant ME intake with time, resulted in a time-dependent relationship between HP and ME intake. Estimated basal metabolic rate and efficiency of ME utilization below maintenance decreased with time, whereas the maintenance requirement remained virtually unchanged (134 kcal.kg-.75.d-1). The influence of feeding level on energy metabolism in young calves increased with time. For at least 12 d after transportation the energy metabolism of young calves had not reached steady-state levels. PMID- 1506313 TI - Progesterone production by cultured luteal cells in the presence of bovine low- and high-density lipoproteins purified by heparin affinity chromatography. AB - The objectives of this study were to separate plasma lipoprotein particles based on the presence (low-density lipoproteins; LDL) or absence of apolipoprotein B (high-density lipoproteins; HDL) and to compare the abilities of bovine LDL and HDL to stimulate progesterone production by bovine luteal cells in culture. Plasma lipoproteins were isolated by ultracentrifugation and separated into LDL and HDL by heparin affinity chromatography. Luteal cultures were treated with LDL or HDL cholesterol for 48 h on d 3 of the culture (d 0 = day of dissociation). Progesterone production by luteal cells increased in a dose-dependent manner with increasing concentrations of either LDL or HDL cholesterol. There were no differences in the ability of LDL or HDL cholesterol to stimulate luteal cells to produce progesterone. Because LDL and HDL were equally potent, and experiment was designed to investigate the ability of modified LDL or reconstituted particles without apolipoproteins to stimulate progesterone production. Stimulation of luteal cell progesterone production by lysine-modified LDL was 70% of unmodified LDL. Progesterone production in the presence of phosphatidylcholine liposomes or BSA containing cholesterol was 50 and 108% of that obtained with HDL or LDL. Evidence indicated that apolipoprotein-free particles that contained free cholesterol but not cholesterol esters stimulated luteal cells to produce progesterone. PMID- 1506315 TI - Digestion, feed intake, and live weight gain by cattle consuming bermudagrass hay supplemented with whey. AB - Three experiments were conducted with cattle consuming bermudagrass hay to determine whether low-level supplements of whey alone, corn alone, or whey plus corn affect feed intake, digestion, and(or) BW gain. Six ruminally and duodenally cannulated beef cows (574 kg), used in a Latin-square trial (Exp. 1), were fed bermudagrass hay without supplementation (control) or with 2.8% whey (low whey, LW), 5.6% whey (high whey, HW), 17.4% ground corn (C), 2.8% whey plus 14.9% corn (C-LW), or 5.6% whey plus 12.4% corn (C-HW). Supplementing with whey and(or) corn increased ruminal butyrate (8.8, 9.4, 10.0, 9.6, 10.5, and 11.0 mol/100 mol of total VFA for control, LW, HW, C, C-LW, and C-HW, respectively; SE = .20). Supplements did not affect microbial N flow at the duodenum. Six Holstein steer calves (158 kg) in a Latin square (Exp. 2) consumed bermudagrass hay ad libitum alone (control) or with .075 or .15% BW whey (LW and HW, respectively), .5% BW ground corn (C), or corn-whey mixes made by substituting whey for corn (C-LW and C-HW). Substituting .15% BW of whey for corn increased (P less than .05) total OM intake slightly (3.99, 3.84, 3.75, 4.11, 4.28, and 4.47 kg for control, LW, HW, C, C-LW, and C-HW, respectively; SE = .10). In an 84-d randomized block experiment (Exp. 3), 96 beef calves (194 kg) consumed (ad libitum) low-quality bermudagrass hay alone or with C, LW, HW, C-LW, or C-HW supplements.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1506316 TI - Cattle blood plasma and red blood cell alpha-tocopherol levels in response to different chemical forms and routes of administration of vitamin E. AB - The chemical form and site of administration of vitamin E were assessed in cattle by measuring area under the time curve alpha-tocopherol levels in plasma and red blood cells (RBC). In Exp. 1, four groups of Holstein calves, 4 to 6 d old, received daily one of the following forms equivalent to 228 mg of alpha tocopherol: D-alpha-tocopheryl acetate (DTA); DL-alpha-tocopheryl acetate (DLTA); D-alpha-tocopheryl polyethylene glycol 1,000 succinate (TPGS); and an experimental blend (EB) containing DTA and TPGS. A control group received no supplement. Temporal alpha-tocopherol responses were determined in blood samples collected for 35 d. Relative to controls whose plasma and RBC alpha-tocopherol levels remained unchanged, all supplementation increased (P less than .05) alpha tocopherol levels in plasma and RBC in calves; the highest levels occurred in those that received either DTA or EB. In a second experiment, five Hereford steers with ruminal and duodenal cannulas were used in a crossover design to determine whether site of vitamin E administration affected plasma alpha tocopherol levels. A single dose of 810 mg of DTA was placed daily into the rumen, and the same amount divided into five equal doses was given (into the duodenum) during a 12-h period. Plasma alpha-tocopherol levels were higher (P less than .05) when steers were ruminally dosed than when they were dosed duodenally. The results suggest that the alpha-tocopherol concentration of plasma and red blood cells in cattle depends on both the chemical form and on the site of administration. PMID- 1506317 TI - Bioavailability of vitamin E compounds in lambs. AB - A study was carried out to assess the bioavailabilities of several forms of vitamin E in lambs. A total of 40 lambs was allotted to eight dietary groups of five each and supplemented or not daily for 60 d with equimolar amounts of different vitamin E compounds as follows: 1) control, no supplemental vitamin E, 2) DL-alpha-tocopheryl acetate, 3) D-alpha-tocopheryl acetate, 4), D-alpha tocopheryl succinate, 5) D-alpha-tocopheryl polyethylene glycol 1,000 succinate (TPGS), 6) DL-alpha-tocopheryl nicotinate, 7) DL-alpha-tocopheryl nicotinate+ TPGS, or 8) D-alpha-tocopheryl acetate + TPGS. During these 60 d, serum alpha tocopherol concentrations in the control lambs remained constant and lower (P less than .05) than in lambs that received all treatments. Various indices of bioavailability, including Cmax-C(i) (concentration maximum-concentration initial), Ct-C(i) (concentration terminal-concentration initial), areas under the serum concentrations profiles, and pooled increment were higher (P less than .05) with D-alpha-tocopheryl acetate+ TPGS than in the other groups, suggesting a synergism between these forms. No such effect was observed between nicotinate and TPGS. For the TPGS, a water-soluble form of vitamin E, the indices of bioavailability were lower (P less than .05) than for the other groups. D-alpha tocopheryl acetate resulted in a bioavailability that outranked all the other forms of vitamin E, except those of D-alpha-tocopheryl acetate + TPGS. A slightly higher bioavailability index was observed for D-alpha-tocopheryl succinate than for DL-alpha-tocopheryl nicotinate.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1506318 TI - Serum alpha-tocopherol concentration in sheep after intramuscular injection of DL alpha-tocopherol. AB - Forty-three crossbred wethers weighing 35 to 60 kg were used to investigate the effect of a single i.m. injection of DL-alpha-tocopherol (DL-alpha-ol). Animals were offered 1 kg/d of a basal diet containing 25 ppm of vitamin E. Lambs were randomly assigned to one of five DL-alpha-ol injection treatments as follows: 1) control (placebo, 0 IU), 2) 125 IU, 3) 250 IU, 4) 500 IU, or 5) 1,000 IU. Blood samples were taken via jugular venipuncture on d 1 before treatment administration and thereafter at designated intervals up to 360 h postinjection. The i.m. injections of DL-alpha-ol irrespective of dose increased serum alpha tocopherol. Results showed a dose x time interaction (P less than .0001) across all treatments. Serum alpha-tocopherol increased rapidly to maximum concentration during the first 8 to 12 h for all non-zero treatments, followed by a rapid decline to pretreatment values. The mean serum alpha-tocopherol concentration at 0 h was .69 microgram/mL. Estimated peak serum alpha-tocopherol concentrations +/ SE were 6.68 +/- 1.04, 9.62 +/- 1.04, 21.66 +/- 2.37, and 50.75 +/- 7.05 micrograms/mL for Treatments 2 through 5, respectively. Results showed a quadratic dose effect (P less than .0003) on maximum response with apparently no effect on time taken to reach this peak. There was also a quadratic dose effect (P less than .0001) on the area under the concentration-time curve. The time taken for serum alpha-tocopherol to return to pretreatment levels increased with dose (56, 64, 67, and 74 h, respectively).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1506319 TI - alpha-Tocopherol concentrations in serum and tissues of sheep fed different sources of vitamin E. AB - Thirty-five crossbred wethers were used to determine the concentrations of alpha tocopherol in serum and tissues after oral supplementation of six different vitamin E product forms. Five wethers were assigned to each of the following treatments: 1) control, no supplemental vitamin E (C), 2) emulsifiable DL-alpha tocopheryl acetate-dry (Rovimix E-50% SD), 3) nonemulsifiable DL-alpha-tocopheryl acetate-dry (Rovimix E-50% Ads), 4) emulsifiable DL-alpha-tocopheryl acetate liquid (Rovimix E-40% Dispersible Liquid Concentrate [DLC]); 5) emulsifiable DL alpha-tocopherol-liquid (Hoffmann-La Roche, E-40% DLC alcohol), 6) micellized DL alpha-tocopheryl acetate-liquid (Bioglan, Inc., E-20%); and 7) micellized DL alpha-tocopherol-liquid (Bioglan, Inc., E-20%). Animals were supplemented daily with 1,000 IU of their respective vitamin E sources for 56 d. Blood samples were collected daily from d 0 to 7 and weekly until d 56. Animals were subsequently killed by exsanguination after stunning and eight different tissues were collected for alpha-tocopherol analysis. There were effects of day, treatment, and day x treatment interaction on serum alpha-tocopherol. All supplemented groups were higher in serum alpha-tocopherol concentration than were the C wethers. The emulsifiable vitamin E alcohol liquid product form (Treatment 5) yielded higher (P less than .01) serum alpha-tocopherol concentration than the emulsifiable acetate liquid product (Treatment 4). Sheep on Treatment 5 reached maximum concentration on d 1, sheep on Treatment 6 on d 2, and the sheep on the remaining Treatments by d 3. Blood sera alpha-tocopherol concentrations stabilized by d 6 in all supplemented groups.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1506320 TI - Combinations of rendered protein meals for growing calves. AB - Complementary responses between rendered protein meals were investigated in this study. In a preliminary trial using 12 mature wethers in two replications, there was no difference (P greater than .20) in N digestibility between meat and bone meal (MBM; 96.7%), feather meal (FTH; 89.8%), and soybean meal (SBM; 98.7%). In a 112-d growth trial, individually fed calves (n = 120; 230 kg) received graded levels of FTH, MBM, 50:50 MBM-FTH (CP basis), or SBM with or without tryptophan (Trp) supplementation. Additions of Trp increased plasma Trp levels (P less than .05) but failed to improve efficiency of protein utilization (P greater than .35). Pooled results showed that this efficiency was greater (P less than .05) for FTH (1.47) than for MBM (1.04), FTH:MBM (.80), or SBM (.66). A trial was conducted to determine whether Trp addition reduces growth response to FTH:MBM (50:50) combinations. Calves (n = 230; 285 kg) were blocked by sex and weight into six replications and received FTH:MBM supplying 35% of the supplemental CP fed alone or with a high or low level of Trp supplement. Negative (urea only) and positive controls were included. Calves receiving FTH:MBM combinations gained faster (P less than .10) and were more efficient (P less than .10) than urea supplemented calves. Performance was not altered by Trp addition. Calves (n = 120; 230 kg) were individually fed in two replications (43 or 48% CP MBM in Replications 1 and 2, respectively) of a growth trial to determine whether there was a complementary response between blood meal (BM) and MBM.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1506321 TI - Basic science and applied science instruction: are they compatible? AB - Basic science and applied science instruction are compatible and essential for animal science professionals to succeed in their chosen career. Application of science is a continuum. Although production methods are constantly evolving, the science on which changes are made is fixed and fundamental. Only our understanding changes. We are educating students in preparation for a life-long learning process. Viability of animal science departments depends on attracting and challenging students with curricula that are demanding, create curiosity, and prepare students to understand the "whys and hows" of the phenomena of animal biology. PMID- 1506322 TI - Modernizing the animal science curriculum: is change needed? AB - To identify an animal science curriculum is difficult because it is a "moving target" due to changing needs and demands of our society and, more specifically, to changes in the backgrounds and interests of students. Therefore, animal science curriculums not only should change, but must change, if they are to succeed. With new technological innovations and discoveries that either modify, supplement, or change basic concepts and approaches, it is paramount that changes in courses as well as in the curriculum conform. Because of the applied nature of animal science and because of the many unknowns yet to be discovered, the curriculum should be under continual scrutiny. However, we must not fix something when it is not broken. For all practical purposes, a curriculum reflects a philosophy of what subjects should be included to complete a plan of study. After a philosophy has been established the base curriculum will seldom change significantly. When it does, it will be the result of a change in people's philosophies rather than a reflection of industry needs or student interests. Teachers should not forget how to teach most effectively the material and must never lose sight of their goal of molding students into knowledgeable, wise, and responsible citizens in our society.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1506323 TI - Comment on the technical note by Baldwin and Jesse. PMID- 1506324 TI - Purification and characterization of an imipenem hydrolysing metallo-beta lactamase from Bacteroides fragilis. AB - An imipenem resistant beta-lactamase producing strain of Bacteroides fragilis was isolated from a clinical specimen. The specific activity of the unpurified beta lactamase was 5.5 U/mg protein. The beta-lactamase was purified 60-fold by Q Sepharose, Sephacryl S-300 and Mono Q column passages. The strain was able to inactivate imipenem and cefoxitin in broth cultures. The enzyme hydrolysed imipenem more rapidly than ampicillin, benzylpenicillin, cephalothin and cefoxitin. The activity of the enzyme was Zn2+ dependent and was completely inhibited by EDTA. The inhibition was reversed by ZnSO4. Preincubation with the common beta-lactamase inhibitors clavulanic acid, sulbactam and tazobactam did not reduce the enzyme activity. The molecular weight was determined by sodium dodecyl sulfate gradient gel electrophoresis to be 31,000 Daltons and the isoelectric point was 4.5. PMID- 1506325 TI - Proposed mechanism for metronidazole resistance in Helicobacter pylori. AB - Metronidazole MIC values were determined for ten isolates of Helicobacter pylori. Under microaerobic conditions four were inhibited by less than 0.25 mg/L, two strains required 2.0 mg/L and four strains had MIC greater than 32 mg/L. The strains were tested for their susceptibility to metronidazole after varying lengths of anaerobic exposure prior to or during microaerobic incubation. The susceptibility was determined by E-test and traditional agar dilution technique. The level of susceptibility of primarily susceptible strains was not significantly affected by a 2 to 24 h period of anaerobic incubation. However, the effect on resistant strains was dramatic. These strains were increasingly susceptible when a 2 to 12 h period of anaerobicity was provided anytime during the first 48 h and fully susceptible (MIC less than 0.1 mg/L) if 24 h of anaerobicity was provided. When tested again under microaerobic conditions the strains exhibited their original MIC values. The composition of the medium did not influence the results. We propose that "metronidazole resistance" in H. pylori is due to a decreased ability of these strains to achieve a sufficiently low redox potential under microaerobic conditions for the necessary reduction of metronidazole, and that these strains during short periods of anaerobicity manage to reduce and "store" sufficient amounts of metronidazole to appear fully susceptible after subsequent microaerobic incubation. microaerobic incubation. PMID- 1506326 TI - Maintenance requirements of Escherichia coli ATCC 25922 in the presence of sub inhibitory concentrations of various antibiotics. AB - Escherichia coli ATCC 25922 was grown in minimal medium M63, with glucose 0.1 gL as limiting energy substrate, in the presence of sub-inhibitory concentrations of netilmicin, habekacin, tobramycin, dibekacin, amikacin, kanamycin, amoxycillin, ampicillin, cephalothin, cefoxitin and nalidixic acid. Maintenance requirements were determined with a simple relationship derived from batch growth curves. The apparent relationship between maintenance requirements and antibiotic concentration is an exponential increase, log m(c) = log mo + k.c, where m is maintenance, c antibiotics concentration, mo maintenance without antibiotics, and k a constant. Values for k were found to be in the range 0.5-2.0 mg-1.L. PMID- 1506327 TI - The postantifungal effect of 5-fluorocytosine on Candida albicans. AB - The in-vitro postantifungal effect (PAFE) of 5-fluorocytosine for Candida albicans for short periods of time was investigated. Yeast cells were exposed for 0.5, 1 or 2 h to a range of concentrations (0.1-3.2 mg/L) of 5-fluorocytosine. The PAFE was quantitated by determinations of the number of colony forming units at hourly intervals (0-10 h) after removal of the drug by dilution. The length of the PAFE was dependent upon the concentration of 5-fluorocytosine and the duration of exposure. An exposure time of 0.5 h resulted in PAFE's ranging from 0 to 4.2 h. Exposure times of 1 and 2 h resulted in longer PAFEs and in many instances suppression of cell growth was seen for the entire evaluation period (up to ten hours). PMID- 1506328 TI - The IC50: an exactly defined measure of antibiotic sensitivity. AB - The concentration of gentamicin that inhibits the growth of half of an inoculum of Pseudomonas aeruginosa (IC50) was estimated by doing viable bacterial counts with varying concentrations of gentamicin and fitting a probit inhibition curve to the results. This is a more precisely defined measure than the MIC and its standard error is readily calculable. PMID- 1506329 TI - In-vitro activities of 14-, 15- and 16-membered macrolides against gram-positive cocci. AB - The in-vitro activities of the 14-membered macrolides erythromycin, dirithromycin, roxithromycin, clarithromycin, the 15-membered compound azithromycin and the 16-membered macrolides (16 MM) josamycin, spiramycin and midecamycin acetate (MOM) have been compared against staphylococci, enterococci and streptococci. Results have been analysed separately according to the sensitivity status of the tested strains to erythromycin, namely sensitive (S), inducibly resistant (IR) or constitutively resistant (CR). 14- and 15-membered macrolides were active only against S strains; the order of potency in vitro was clarithromycin = erythromycin greater than azithromycin = roxithromycin greater than dirithromycin. The 16 MM were slightly less active against S strains than were the 14- and 15-membered compounds, and inhibited most IR strains; MOM and josamycin were about twice as potent as spiramycin. IR and S Staphylococcus aureus strains were equally sensitive to 16 MM, while IR strains of coagulase negative staphylococci were less sensitive than were S strains. All CR strains of S. aureus were resistant to 16 MM, as were most of the other CR strains. However, 5/21 CR coagulase-negative staphylococci and 2/20 CR enterococci tested were sensitive to 16 MM. The seven CR strains showing anomalous sensitivity to the 16 MM (five Staphylococcus haemolyticus and two enterococci) were only 'moderately resistant' to erythromycin (MIC 8-64 mg/L), while all the other CR strains were 'highly resistant' (MIC greater than 128 mg/L). These results indicate that it may be difficult to predict the sensitivity of Gram-positive cocci to 16 MM, and therefore individual sensitivity testing to specific compounds is essential. PMID- 1506330 TI - Surveillance of Streptococcus pneumoniae serotypes in Riyadh and their susceptibility to penicillin and other commonly prescribed antibiotics. AB - A total of 358 recent distinct isolates of Streptococcus pneumoniae were recovered from clinical specimens of patients in various hospitals in Riyadh, Saudi Arabia. The commonest serotypes were Groups C, F, B and A. Using specific monosera for typing it was found that serotype 14 was the commonest followed by serotypes 3, 7, 1, 2, 19 and 8 respectively. The minimal inhibitory concentrations (MIC) of penicillin determined by an agar dilution method, showed that 81% were susceptible (MIC less than 0.1 mg/L), 18% were relatively resistant (MIC = 0.1-1 mg/L) and 1% showed increased resistance (MIC greater than or equal to 1.0 mg/L). The use of a 1 microgram oxacillin disc distinguished between susceptible and relatively penicillin resistant pneumococci more reliably than did the use of a penicillin disc (1 or 10 micrograms). Resistance of S. pneumoniae to tetracycline, co-trimoxazole, chloramphenicol, and erythromycin were 70%, 43%, 12% and 4% respectively. All isolates were susceptible to oral cephalosporins (cefadroxil, cephalexin, cefaclor, and cefuroxime axetil) with an MIC range of less than or equal to 0.03-2 mg/L. The selection of antimicrobial therapy and the efficiency of vaccines depend on the knowledge of the local isolates of S. pneumoniae. Clinical isolates should be routinely screened to detect susceptibility to penicillin. The relatively high incidence of resistance to multiple antibiotics indicates the need to perform antibiotic susceptibility testing in order to avoid possible therapeutic failure. PMID- 1506331 TI - The spectrum of antibiotic resistance in human and veterinary isolates of Escherichia coli collected from 1984-86 in northern India. AB - This study was undertaken to assess the spectrum of drug resistance prevalent in Escherichia coli isolates from human and animal populations in Northern India. Three hundred and two isolates of Escherichia coli isolated from various infections of humans (47 from diarrhoea; 101 from urinary tract infection) and veterinary animals (17 from poultry septicaemia; 75 from bovine diarrhoea; 14 from ovine diarrhoea and 48 from equine metritis) were studied for their susceptibility to ampicillin, cephaloridine, amoxycillin, cloxacillin, oxytetracycline, doxycycline, chloramphenicol, gentamicin, and trimethoprim sulphamethoxazole. 63.2% of the isolates (37.7%, human; 25.5%, animal) were resistant to one or more drugs, of which about 41% isolates were multiresistant. Resistant isolates had a wide range of MIC values from 12 to 3200 mg/L, irrespective of origin. Most of the isolates (43.5%) were resistant to ampicillin (MIC greater than 16 mg/L) followed by oxytetracycline (MIC greater than 5 mg/L) (36.4%). Only 9.3% isolates were resistant to trimethoprim-sulphamethoxazole (MIC greater than 21 mg/L). The E. coli isolated from animals tended to be resistant to fewer antibiotics than those isolated from man. 99% of the isolates from human urinary tract infection were resistant compared to only 48.9% of the isolates from diarrhoea. Most of the resistant isolates from animals were recovered from diarrhoea, followed by septicaemia and metritis. This study shows that a high frequency of multiresistant strains are prevalent in both human and animal bacterial populations of Northern India. Since the exchange of these strains among both populations is possible, they pose a great risk in both the selection and the spread of resistance. PMID- 1506332 TI - In-vitro activity of new carbapenem antibiotics: comparative studies with meropenem, L-627 and imipenem against pathogenic Nocardia spp. AB - MICs of two new carbapenems, meropenem and L-627, and imipenem were determined against 98 strains of the Nocardia asteroides group (i.e. N. asteroides sensu stricto, Nocardia farcinica and Nocardia nova), 46 strains of Nocardia brasiliensis and 17 strains of Nocardia otitidiscaviarum. Meropenem and L-627 were less active against the N. asteroides group than imipenem. Among the three species of the N. asteroides group, N. nova was the most sensitive to all the carbapenems. Meropenem was more active than imipenem against both N. brasiliensis and N. otitidiscaviarum with MIC50 values of 28.3-53.3 mg/L. L-627 was less active than meropenem. PMID- 1506333 TI - Effect of erythromycin on ciliary motility in rabbit airway epithelium in vitro. AB - The effect of erythromycin on ciliary beat frequency (CBF) of rabbit tracheal epithelium was studied by a microphoto-oscillation technique in vitro. Addition of erythromycin dose-dependently increased CBF, the maximal increase from the baseline value and EC50 being 23.3 +/- 4.5% (P less than 0.001) and 6.8 +/- 0.9 mg/L, respectively. This effect was not influenced by autonomic receptor antagonists, blockers of arachidonic acid metabolism, Ca(2+)-free medium, or inhibition of protein kinase C and protein kinase A activities. PMID- 1506334 TI - Pharmacokinetics and metabolism of FCE 22101 following its administration as the oral pro-drug FCE 22891. AB - Ten healthy male volunteers who had previously received both intramuscular and intravenous doses of FCE 22101 received a single oral dose of FCE 22891, the acetoxymethyl ester and pro-drug of FCE 22101. After a lag time of 22 min, mean plasma levels of FCE 22101 rose with a T1/2 absorbance of 19 min to 2.5 mg/L at 30 min, 3.6 mg/L at 60 min and a Cmax of 4.6 mg/L at 80 min; levels then fell with a T1/2 beta of 29 min to be undetectable at 300 min. The mean area under the concentration-time curve (AUC) was 497 mg.min/L giving an absolute bioavailability for FCE 22101 of 32%. Neither FCE 22101 or its metabolites were present in any of the saliva samples collected at intervals up to 360 min after dosing. Mean urinary recoveries were FCE 22101 12% (+/- S.D. 4.6), P1 16% (+/- S.D. 9.1) and P2 3.3% (+/- S.D. 2.1). It was not possible to detect the pro-drug FCE 22891 in any of the blood or urine samples. Significant levels of the metabolite P1 were observed in blood with peak levels of 1.7 mg/L seen 130 min after dosing, 50 min later than the peak FCE 22101 levels, and giving a mean AUC of 297 mg.min/L. PMID- 1506335 TI - Awareness of need and actual use of prophylaxis: lack of patient compliance in the prevention of bacterial endocarditis. AB - Antibiotics are given before some medical and dental procedures to patients with congenital or acquired heart disease to prevent endocarditis. The majority of practitioners and patients are aware of the need for this prophylaxis, although in practice prophylaxis is administered infrequently. It is not known how often patients at risk for endocarditis undergo procedures which warrant the prophylactic administration of antibiotics, nor how often prophylaxis is actually administered to these patients. Two groups of adult patients and a group of children with a cardiac lesion predisposing to endocarditis were surveyed by either telephone interview or mailed questionnaire about awareness of the need for prophylaxis, procedures undergone within six months of the survey and the actual use of prophylaxis before these procedures. Of 455 patients surveyed, 371 (81.5%) responded, 258 (69.5%) of whom remembered receiving advice on prophylaxis. Recollection of advice ranged from 77% of those younger than sixty years to 48% of those aged sixty or older. The patients underwent 68 procedures for which prophylaxis was definitely indicated and 71 procedures with a possible indication for prophylaxis; 127 (91%) of these procedures were dental. Antibiotics were allegedly administered before the procedure to 31 patients (22%). There is marked discrepancy between recollection of the advice and actual use of prophylaxis. In view of this it is likely that patients often undergo procedures without antibiotic protection; however, only a few of these patients develop endocarditis. PMID- 1506336 TI - A comparison of the costs of ceftazidime therapy and gentamicin combinations in three UK hospitals. AB - This study compares the utilization costs of ceftazidime therapy with those of gentamicin in combination with other antibacterial drugs. The results show that the relatively high purchase cost of ceftazidime compared to combinations is more than counterbalanced by the additional materials used for drug administration and serum antibiotic assays, even when other drugs were combined with ceftazidime. The average drug and equipment costs were 230.13 pounds for ceftazidime regimens and 253.94 pounds for gentamicin regimens. It is also shown that ceftazidime therapy is associated with a reduction in personnel time compared to gentamicin regimens. The average times per patient for administration and assay were 1 h 43 min for ceftazidime and 4 h 57 min for gentamicin regimens. We conclude that ceftazidime regimens are cheaper than gentamicin regimens when all drug and equipment costs are quantified. Moreover, the use of ceftazidime will release staff time for other purposes. PMID- 1506337 TI - Terminology of Staphylococcus aureus strains showing decreased susceptibility to methicillin. PMID- 1506338 TI - The outer membrane as the penetration barrier against mupirocin in gram-negative enteric bacteria. PMID- 1506339 TI - Activity of sulbactam combinations against Escherichia coli isolates with known amounts of TEM-1 beta-lactamase. PMID- 1506340 TI - Prediction of ofloxacin susceptibility from in-vitro tests with ciprofloxacin. PMID- 1506341 TI - Antibiotic susceptibility of Enterobacteriaceae isolated from patients in northern Tanzania. PMID- 1506342 TI - Killing of ofloxacin-exposed pneumococci by human neutrophils. PMID- 1506343 TI - Antibiotics in the treatment of peptic ulcer disease. PMID- 1506344 TI - Carbapenemases. PMID- 1506345 TI - New insights into the pathophysiology of the Jarisch-Herxheimer Reaction. PMID- 1506346 TI - Effect of subinhibitory antimicrobial concentrations (sub-MICs) on in-vitro bacterial adherence to uroepithelial cells. AB - Subinhibitory antimicrobial concentrations have been reported to alter the adherence of bacteria to uroepithelial cells. Most investigators assessing the influence of subinhibitory antimicrobial concentrations on bacterial adherence in the urinary tract have employed in-vitro techniques using voided uroepithelial cells. These cells are incubated with bacteria previously exposed to antimicrobials and adherence is assessed by light microscopy. Most investigators have studied urinary Escherichia coli isolates. beta-Lactams, tetracyclines, aminoglycosides, nitrofurantoin, chloramphenicol, quinolones, trimethoprim and sulphonamides have been studied in concentrations ranging from 1/32-1/2x MIC. The following effects of subinhibitory antimicrobial concentrations on bacterial adherence have been reported: penicillins consistently reduce bacterial adherence at concentrations 1/4-1/2x MIC; nitrofurantoin and chloramphenicol demonstrate variable effects on bacterial adherence at 1/4x MIC; tetracyclines, but not doxycycline, decrease adherence at high concentrations (1/4-1/2x MIC) and increase it at low concentrations (1/8-1/32x MIC); both trimethoprim and sulphonamides consistently decrease bacterial adherence at concentrations ranging from 1/32-1/2x MIC and 1/4-1/2x MIC, respectively, but it is unclear whether the combination of trimethoprim and a sulphonamide decreases bacterial adherence to a greater extent than either agent alone; aminoglycosides decrease adherence at 1/2x MIC; and quinolones decrease adherence at 1/4x MIC, with variable effects at 1/8x MIC and 1/16x MIC. Subinhibitory antimicrobial concentrations may exert their antiadhesive effects through suppression of formation and/or expression on the surface adhesin, the formation of functionally aberrant adhesins, or a direct effect on the bacterial surface. Presently, the clinical significance of the alterations in bacterial adherence to uroepithelial cells is not fully understood. PMID- 1506347 TI - Characterization of chromosomally encoded penicillinases in clinical isolates of Klebsiella pneumoniae. AB - Four Klebsiella pneumoniae strains, isolated in two geographically distant French hospitals, were found to produce constitutive beta-lactamases with an unusual isoelectric point for this species (8.1). The four enzymes were chromosomally encoded and related to the Ambler's class A plasmid-mediated SHV-type enzymes. The four enzymes were predominantly penicillinases, with good activity against amino- and ureidopenicillins. They poorly hydrolysed cephalothin, cephaloridine and cefoperazone and did not hydrolyse third-generation cephalosporins and aztreonam. The four enzymes were susceptible to the inhibitory effect of clavulanic acid. Finally, the strains were all found to produce an acetyl esterase. The acetyl-esterases catalysized hydrolysis of the acetoxy group of cephalothin and cefotaxime although this did not affect their antibacterial activities. These esterases were not susceptible to the inhibitory effect of clavulanic acid and EDTA. PMID- 1506348 TI - In-vitro activity of tosufloxacin, a new quinolone antibacterial agent. AB - The in-vitro activity of tosufloxacin (A-61827) was compared with that of temafloxacin, ciprofloxacin and selected members of other groups of antimicrobial agents, against 684 recent distinct clinical isolates and strains with known mechanisms of resistance. Against members of the Enterobacteriaceae, ciprofloxacin was slightly more active than tosufloxacin, which was more active than temafloxacin. The MIC90 of tosufloxacin for all species of Enterobacteriaceae, Pseudomonas aeruginosa and Acinetobacter spp. was less than or equal to 1 mg/L. Tosufloxacin was slightly more active than temafloxacin, and four to eight fold more active than ciprofloxacin, against the Gram-positive species tested. The MIC90 of tosufloxacin for Staphylococcus aureus was 0.12 mg/L, and for Streptococcus pneumoniae was 0.5 mg/L. All strains of Neisseria spp., Haemophilus influenzae and Moraxella catarrhalis were inhibited by tosufloxacin at a concentration of less than or equal to 0.12 mg/L. Tosufloxacin was the most active quinolone against the anaerobic organisms tested. Cross resistance between quinolones was seen, but not between quinolones and other groups of antimicrobials. The protein binding of tosufloxacin across a range of concentrations averaged 60%. Human serum at a concentration of 70% decreased the bactericidal activity of tosufloxacin by about four-fold. PMID- 1506349 TI - Comparison of the in-vitro activities of the topical antimicrobials azelaic acid, nitrofurazone, silver sulphadiazine and mupirocin against methicillin-resistant Staphylococcus aureus. AB - The in-vitro activities of the topical agents azelaic acid, nitrofurazone, silver sulphadiazine and mupirocin have been determined against 80 strains of MRSA collected from worldwide sources. MICs were determined by agar dilution (with an inoculum of approximately 5.0 x 10(5) cfu) in Iso-Sensitest agar, and MBCs were measured by replica-plating from MIC plates using velvet pads. The agents tested were uniformly active against MRSA, mupirocin being the most active (MIC50 0.15 mg/L) followed by nitrofurazone (MIC50 19 mg/L), silver sulphadiazine (MIC50 85 mg/L) and azelaic acid (MIC50 850 mg/L). Concentrations of azelaic acid, nitrofurazone and silver sulphadiazine close to the MIC were bactericidal, but mupirocin was only bactericidal at concentrations substantially greater than the MIC. In time-kill experiments, azelaic acid and nitrofurazone were gradually bactericidal, silver sulphadiazine was rapidly bactericidal and mupirocin was not bactericidal. Silver sulphadiazine killed sulphonamide-sensitive and sulphonamide resistant strains equally rapidly. No resistant mutants were found to azelaic acid, nitrofurazone or silver sulphadiazine in an inoculum of 10(9) cfu, but two strains yielded (frequency: 1.0 x 10(-9)) mutants resistant to mupirocin. Our in vitro results suggest azelaic acid, nitrofurazone and silver sulphadiazine could be of use for clearing staphylococcal carriage. PMID- 1506350 TI - Effect of impaired renal function on the pharmacokinetics of coadministered cefoperazone and sulbactam. AB - The pharmacokinetics of cefoperazone 2 g combined with sulbactam 1 g after a single dose administered intravenously were evaluated in 24 subjects with normal and impaired renal function. Subjects were categorized into four groups based on endogenous creatinine clearance Clcr. Patients in groups 1, 2 and 3 had ClcrS of greater than 60, 31 to 60, and 10 to 30 mL/min/1.73 m2, respectively. Patients in group 4 required maintenance haemodialysis and were assumed to have Clcr less than 10 mL/min/1.73 m2. Pharmacokinetic parameters were determined by noncompartmental methods. No significant differences (P greater than 0.05) in mean peak serum cefoperazone-sulbactam concentrations for group 1 (208.4/29.0 mg/L), group 2 (199.0/34.1 mg/L), group 3 (163.2/35.0 mg/L), and group 4 (234.0/66.0 mg/L) were noted. Correlations between both total serum (r = 0.58) and renal (r = 0.35) clearance and creatinine clearances were negative for cefoperazone, although both were shown to decline with diminished renal function. Correlations between serum (r = 0.85) and renal (r = 0.72) clearances and creatinine clearance for sulbactam were, on the other hand, both positive and declined in a linear fashion. No significant differences in steady state volumes of distribution were noted for either cefoperazone (P = 0.53) or sulbactam (P = 0.85) amongst the four groups. After 24 h, urinary recovery was also comparable for both cefoperazone (P = 0.64) and sulbactam (P = 0.85) amongst the four groups. The concentrations of cefoperazone and sulbactam remained at or above the MICs (16/8 mg/L) for common bacterial pathogens for 2.5, 3, 7 and 14 h in groups 1, 2, 3 and 4, respectively. PMID- 1506351 TI - A study of the penetration of meropenem into bile using endoscopic retrograde cholangiography. AB - One gram of meropenem was administered as prophylaxis to patients undergoing endoscopic retrograde cholangiography (ERC) in a study of the bile pharmacokinetics of this agent. Twenty-four patients were evaluated and a single bile sample was collected from each one during ERC at different time intervals following intravenous infusion. Bile concentrations after the dose ranged from 0.7 to 25.7 mg/L (mean 11.1) and exceeded the MIC90s for the pathogens most commonly associated with biliary tract infections for up to 203 mins. The bile concentrations of 13 patients with biliary tree obstruction were compared with those of 11 patients without obstruction. Bile concentrations in excess of the MIC90s for the predominant pathogens were achieved in both groups; a positive correlation between meropenem bile concentration and the time of dose administration was demonstrable only for the obstructed group. ERC may be a useful technique for biliary pharmacokinetic studies. PMID- 1506352 TI - Penetration of rifampicin into the cerebrospinal fluid of adults with uninflamed meninges. AB - The penetration of rifampicin into CSF was studied in seven patients who had undergone external ventriculostomy for occlusive hydrocephalus without major disturbance of the blood-CSF barrier. After the first dose of rifampicin 600 mg i.v. over 3 h, blood and CSF concentrations were determined serially by HPLC. Peak CSF concentrations obtained 0-8 h (median = 1 h) after the end of the infusion ranged from 0.57 to 1.24 mg/L (median = 0.73 mg/L). Elimination from CSF was slower than from serum (T1/2 beta CSF: 9.1-21.0 h (median = 14.5 h, n = 5); T1/2 beta serum: 2.2-5.8 h (median = 3.6 h, n = 7)). Based on the ratios of the areas under the concentration-time curves in CSF and serum, the overall penetration of rifampicin into CSF was 0.13-0.42 (median = 0.22). These results demonstrate effective CSF penetration and favourable pharmacokinetics of rifampicin in the absence of meningeal inflammation. They support the use of rifampicin as part of a combination therapy not only for tuberculosis of the central nervous system (CNS), but also for staphylococcal and listerial infections of the CNS in which there may be little meningeal inflammation. PMID- 1506353 TI - Plasmid carriage and related antibiotic resistance in enterococci. PMID- 1506354 TI - High-level aminoglycoside resistance among enterococci isolated from blood cultures. PMID- 1506355 TI - Respiratory and circulatory activities in carotid body-resected humans. AB - The respiratory and circulatory activities of patients who underwent carotid body resection (CBR) more than two decades ago were reviewed. No significant ventilatory response to continuous hypoxia was observed. However, in response to stimulation of peripheral chemoreceptors, transient hyperventilation occurred before hypoxemic blood arrived at the central nervous system (single-breath test), which indicated the presence of weak peripheral chemosensitivity. Because of this slight residual peripheral chemosensitivity, which was found shortly after the operation and apparently remained more or less unchanged for greater than 20 years, peripheral chemoreceptor activity, which has been reported in other animal species, does not seem to have returned. Delayed hypoxic hyperventilation reported in dogs and cats with CBR was not observed. Hypoxia significantly depressed the ventilatory response to CO2, but the delayed ventilatory depression with time that has been demonstrated in normal subjects did not occur. In our circulatory studies, hypoxia augmented the heart rate and slightly depressed the stroke volume and total peripheral resistance in the systemic circulation but induced no appreciable changes in arterial blood pressure or cardiac output. We used these results to partition the relative contributions to the overall circulatory response of carotid body stimulation, pulmonary inflation, and other modifying influences. From these calculations, it was inferred that the carotid body reflex plays a dominant role in vascular activities whereas the pulmonary inflation reflex dominates in cardiac activities in humans. PMID- 1506356 TI - Augmented hypoxic ventilatory response in men at altitude. AB - To test the hypothesis that the hypoxic ventilatory response (HVR) of an individual is a constant unaffected by acclimatization, isocapnic 5-min step HVR, as delta VI/delta SaO2 (l.min-1.%-1, where VI is inspired ventilation and SaO2 is arterial O2 saturation), was tested in six normal males at sea level (SL), after 1-5 days at 3,810-m altitude (AL1-3), and three times over 1 wk after altitude exposure (PAL1-3). Equal medullary central ventilatory drive was sought at both altitudes by testing HVR after greater than 15 min of hyperoxia to eliminate possible ambient hypoxic ventilatory depression (HVD), choosing for isocapnia a P'CO2 (end tidal) elevated sufficiently to drive hyperoxic VI to 140 ml.kg-1.min 1. Mean P'CO2 was 45.4 +/- 1.7 Torr at SL and 33.3 +/- 1.8 Torr on AL3, compared with the respective resting control end-tidal PCO2 of 42.3 +/- 2.0 and 30.8 +/- 2.6 Torr. SL HVR of 0.91 +/- 0.38 was unchanged on AL1 (30 +/- 18 h) at 1.04 +/- 0.37 but rose (P less than 0.05) to 1.27 +/- 0.57 on AL2 (3.2 +/- 0.8 days) and 1.46 +/- 0.59 on AL3 (4.8 +/- 0.4 days) and remained high on PAL1 at 1.44 +/- 0.54 and PAL2 at 1.37 +/- 0.78 but not on PAL3 (days 4-7). HVR was independent of test SaO2 (range 60-90%). Hyperoxic HCVR (CO2 response) was increased on AL3 and PAL1. Arterial pH at congruent to 65% SaO2 was 7.378 +/- 0.019 at SL, 7.44 +/- 0.018 on AL2, and 7.412 +/- 0.023 on AL3.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1506357 TI - Effect of tidal volume and PEEP in ethchlorvynol-induced asymmetric lung injury. AB - We examined the effects of positive end-expiratory pressure (PEEP) and tidal volume on the distribution of ventilation and perfusion in a canine model of asymmetric lung injury. Unilateral right lung edema was established in 10 animals by use of a selective infusion of ethchlorvynol. Five animals were tested in the supine position (horizontal asymmetry) and five in the right decubitus position (vertical asymmetry). Raising PEEP from 5 to 12 cmH2O improved oxygenation despite a redistribution of blood flow toward the damage lung and a consistent decrease in total respiratory system compliance. This improvement paralleled a redistribution of tidal ventilation to the injured lung. This was effected primarily by a fall in the compliance of the noninjured lung due to hyperinflation. The effects of higher tidal volume were additive to those of PEEP. We propose that the major effect of PEEP in inhomogeneous lung injury is to restore tidal ventilation to a population of alveoli recruitable only at high airway pressures. PMID- 1506358 TI - Circulating neuropeptide Y does not produce pulmonary hypertension during massive sympathetic activation. AB - We tested the possibility that neuropeptide Y (NPY) may contribute to the pulmonary hypertension that occurs after massive sympathetic activation produced by intracisternal veratrine administration in the chloralose-anesthetized dog. In six dogs, veratrine caused arterial NPY-like immunoreactivity (NPY-LI) to rise from 873 +/- 150 (SE) pg/ml to peak values of 3,780 +/- 666 pg/ml by 60-120 min. (In 3 animals, adrenalectomy significantly reduced the increases in NPY-LI.) In five additional dogs, we infused porcine NPY for 30 min in doses that increased arterial NPY-LI to 8,354 +/- 1,514 pg/ml and observed only minor changes in pulmonary hemodynamics. In three isolated perfused canine left lower lung lobe (LLL) preparations, increasing doses of NPY were administered, producing levels of plasma NPY-LI, at the highest dose, that exceeded those observed after veratrine administration by three orders of magnitude. No changes in LLL arterial or double-occlusion capillary pressures were observed at any dose. Similarly, no changes in LLL hemodynamics were observed in three additional lobes when NPY was administered while norepinephrine was being infused. We conclude that it is unlikely that NPY plays a role as a circulating vasoactive agent in producing the pulmonary hypertension and edema that occur in this model. PMID- 1506359 TI - High lung volume increases stress failure in pulmonary capillaries. AB - We previously showed that when pulmonary capillaries in anesthetized rabbits are exposed to a transmural pressure (Ptm) of approximately 40 mmHg, stress failure of the walls occurs with disruption of the capillary endothelium, alveolar epithelium, or sometimes all layers. The present study was designed to test whether stress failure occurred more frequently at high than at low lung volumes for the same Ptm. Lungs of anesthetized rabbits were inflated to a transpulmonary pressure of 20 cmH2O, perfused with autologous blood at 32.5 or 2.5 cmH2O Ptm, and fixed by intravascular perfusion. Samples were examined by both transmission and scanning electron microscopy. The results were compared with those of a previous study in which the lung was inflated to a transpulmonary pressure of 5 cmH2O. There was a large increase in the frequency of stress failure of the capillary walls at the higher lung volume. For example, at 32.5 cmH2O Ptm, the number of endothelial breaks per millimeter cell lining was 7.1 +/- 2.2 at the high lung volume compared with 0.7 +/- 0.4 at the low lung volume. The corresponding values for epithelium were 8.5 +/- 1.6 and 0.9 +/- 0.6. Both differences were significant (P less than 0.05). At 52.5 cmH2O Ptm, the results for endothelium were 20.7 +/- 7.6 (high volume) and 7.1 +/- 2.1 (low volume), and the corresponding results for epithelium were 32.8 +/- 11.9 and 11.4 +/- 3.7. At 32.5 cmH2O Ptm, the thickness of the blood-gas barrier was greater at the higher lung volume, consistent with the development of more interstitial edema. Ballooning of the epithelium caused by accumulation of edema fluid between the epithelial cell and its basement membrane was seen at 32.5 and 52.5 cmH2O Ptm. At high lung volume, the breaks tended to be narrower and fewer were oriented perpendicular to the axis of the pulmonary capillaries than at low lung volumes. Transmission and scanning electron microscopy measurements agreed well. Our findings provide a physiological mechanism for other studies showing increased capillary permeability at high states of lung inflation. PMID- 1506360 TI - Substrate and endocrine responses during exercise at selected stages of pregnancy. AB - To determine whether the concomitant effects of pregnancy and exercise yield substrate and endocrine patterns different from those expected during exercise alone, we compared the responses of glucose, lactate, free fatty acids, insulin, epinephrine (EP), norepinephrine (NE), human chorionic gonadotropin (HCG), human placental lactogen (HPL), estriol, and progesterone (P) in nonpregnant women (NP; n = 7) and pregnant women in the second (TR2; n = 6) and third trimester (TR3; n = 8) of pregnancy, before, during, and after 30 min of bicycle ergometer exercise at heart rates of 130-140 beats/min. In general, all substrates and hormone concentrations increased with exercise (P less than 0.05), except insulin, which decreased (P less than 0.05), and HCG, which did not change (P = 0.08). Differences in selected hormone concentrations (P, estriol, HCG, and HPL) among groups were already present at rest because of the different stages of pregnancy. Differences among groups at rest were also found in insulin and NE (P less than 0.05). Significantly different responses to exercise (i.e., group x time interactions) were as follows. NP vs. TR2:P, estriol, HCG, HPL, EP, and NE (P less than 0.05); NP vs. TR3: glucose, EP, and NE (P less than 0.05); TR2 vs. TR3: lactate, EP, and NE (P less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1506361 TI - A time-course study of the effects of pentobarbital, fentanyl, and morphine chloralose on myocardial mechanics. AB - Cardiovascular physiological studies in anesthetized animals may be confounded by the hemodynamic actions of the anesthetic agents themselves. To identify an anesthetic regimen that does not significantly influence cardiovascular physiology, the hemodynamic responses of 28 dogs were studied. Animals were equally divided among groups with 1) no anesthesia (i.e., trained conscious preparation), 2) pentobarbital sodium, 3) fentanyl citrate, and 4) a combination of morphine sulfate and alpha-chloralose. Anesthesia was maintained for 3 h. Data were acquired with the use of ultrasound imaging of the heart in conjunction with invasive pressure measurements. Left ventricular ejection phase indexes and end systolic force-velocity relations were used to evaluate the effects of each anesthetic agent on overall systolic performance and myocardial contractility. Compared with the conscious animals, pentobarbital profoundly depressed systolic performance (P less than 0.05 vs. control) because of a reduction in myocardial contractility (P less than 0.01) and an increase in left ventricular afterload (end-systolic wall stress, P less than 0.05). Fentanyl increased myocardial contractility (P less than 0.05) but also tended to increase afterload with the net result that overall systolic performance remained unchanged. Morphine chloralose did not affect overall ventricular systolic performance or its individual determinants. Pentobarbital and fentanyl also caused progressive time dependent deteriorations in all parameters of systolic function during prolonged anesthesia. In contrast, cardiac function was stable for greater than or equal to 3 h after induction of morphine-chloralose anesthesia. The hemodynamic profile of dogs anesthetized with morphine-chloralose most closely resembled that of the conscious animals. Morphine-chloralose is recommended when prolonged anesthesia is required for studies of cardiovascular physiology. PMID- 1506362 TI - Capillary and fiber geometry in rat diaphragm perfusion fixed in situ at different sarcomere lengths. AB - To determine the potential range of diaphragm sarcomere lengths in situ and the effect of changes in sarcomere length on capillary and fiber geometry, rat diaphragms were perfusion fixed in situ with glutaraldehyde at different airway pressures and during electrical stimulation. The lengths of thick (1.517 +/- 0.007 microns) and thin (1.194 +/- 0.048 microns) filaments were not different from those established for rat limb muscle. Morphometric techniques were used to determine fiber cross-sectional area, sarcomere length, capillary orientation, and capillary length and surface area per fiber volume. All measurements were referenced to sarcomere length, which averaged 2.88 +/- 0.08 microns at -20 to 25 cmH2O airway pressure (residual volume) and 2.32 +/- 0.05 microns at +20 to +26 cmH2O airway pressure (total lung capacity). The contribution of capillary tortuosity and branching to total capillary length was dependent on sarcomere length and varied from 5 to 22%, consistent with that shown previously for mammalian limb muscles over this range of sarcomere lengths. Capillary length per fiber volume [Jv(c,f)] was significantly greater at residual volume (3,761 +/- 193 mm-2) than at total lung capacity (3,142 +/- 118 mm-2) and correlated with sarcomere length [l; r = 0.628, Jv(c,f) = 876l + 1,156, P less than 0.01; n = 18]. We conclude that the diaphragm is unusual in that the apparent in situ minimal sarcomere length is greater than 2.0 microns.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1506363 TI - Influence of human muscle length on energy transduction studied by 31P-NMR. AB - Muscle contractions at lengths below the optimum for force development were previously found to cause less fatigue than contractions at the optimum length (Lo). Decreased fatigability was suggested to arise from fewer cross-bridge interactions in shortened sarcomeres. In the present study, this suggestion was tested by monitoring energy use of human ankle dorsiflexor muscles during and after contractions at Lo and shortened lengths (Ls) with phosphorus nuclear magnetic resonance spectroscopy. The nuclear magnetic resonance spectra indicated similar rates of ATP use during contractions at Lo and Ls. Phosphocreatine, at an initial concentration of 37 mM, was reduced to an equivalent extent by 2 min of ischemic exercise at Lo (to 2.3 mM) and Ls (to 4.7 mM). Changes in pH (indicating glycolytic ATP production) were also equivalent at Lo and Ls. Exercise caused pH to fall from an initial level of 7.07 to 6.5 at Lo and to 6.53 at Ls. In relation to previous experiments performed under similar conditions on human ankle dorsiflexor muscles, the present experiments suggest that in shortened muscle the decreased force found in this and previous studies and the decreased fatigability that was previously found may not be simply due to fewer cross-bridge interactions in shortened sarcomeres. Examination of the relationships between developed force and levels of metabolites suggests that changes of force during fatigue and recovery correlate better with intracellular [Pi] and H2PO4- than with [H+]. PMID- 1506365 TI - Tumor necrosis factor-alpha does not cause lung edema in rabbits. AB - Although tumor necrosis factor-alpha (TNF) is a key mediator in the pathophysiology of sepsis and septic shock, its role in lung microvascular injury is controversial. In isolated blood-perfused rabbit lungs, we studied the microvascular effects of human recombinant TNF by measuring the capillary filtration coefficient (Kf,c) as an index of microvascular leakiness and the arterial and venous resistances and occlusion pressures to define the microvascular pressure profile. At the end of the experiments, the lung wet-to dry weight ratio (W/D) was determined as an index of edema. TNF increased the pulmonary venous resistance slightly but did not affect Kf,c or W/D. Furthermore, TNF at different doses failed to increase W/D less than or equal to 8 h after in vivo administration. Our data suggest that 1) the pulmonary microvascular response to TNF differs from the systemic response, which is characterized by arteriolar vasodilation, and 2) TNF is insufficient to cause lung edema, both in vivo and in vitro. Thus the development of lung microvascular injury may require the combined action of TNF and other mediators. PMID- 1506364 TI - Effects of cold on vascular permeability and edema formation in the isolated cat limb. AB - We investigated the effects of cold temperatures on microvascular protein permeability in the isolated constant-flow perfused cat hindlimb. The perfusates were 20% cat plasma-80% albumin-electrolyte solution (low-viscosity perfusate, approximately 1 cP) or whole blood (high-viscosity perfusate, approximately 4 cP). The time at low temperature (less than 10 degrees C) was less than 3 h (short term) or greater than 5 h (long term). Decreases in the solvent drag reflection coefficient (sigma f) indicated increases in permeability. The sigma f's were determined with the integral-mass balance method from measurement of changes in protein concentration and hematocrit induced by fluid filtration into the tissues. Short-term cold exposure did not increase permeability with either a low- or a high-viscosity perfusate, whereas long-term exposure with limb temperatures of approximately 5 degrees C significantly increased permeability when the perfusate was whole blood. In addition, we verified our previous prediction that flow had to be reduced to 6-8 ml.min-1.100 g-1 to avoid the hydrostatic edema caused by short-term perfusion with whole blood at approximately 5 degrees C. Also, we found that at approximately 3 degrees C histamine's permeability-increasing effect was totally abolished, whereas at approximately 20 degrees C this effect was partially inhibited. Hence, constant flow perfusion at low temperature with whole blood can cause edema by a pressure dependent mechanism, whereas long-term perfusion with this perfusate at low temperatures can cause a permeability increase that further compounds edema formation. Histamine is not responsible for this permeability increase. PMID- 1506366 TI - Effect of hypothyroidism on myosin heavy chain expression in rat pharyngeal dilator muscles. AB - Although the association between hypothyroidism and obstructive sleep apnea is well established, the effect of thyroid hormone deficiency on contractile proteins in pharyngeal dilator muscles responsible for maintaining upper airway patency is unknown. In the present study, the effects of hypothyroidism on myosin heavy chain (MHC) expression were examined in the sternohyoid, geniohyoid, and genioglossus muscles of adult rats (n = 20). The relative proportions of MHC isoforms present were determined using MHC-specific monoclonal antibodies and oligonucleotide probes. All control muscles showed a paucity of type I MHC fibers, with greater than 90% of fibers containing fast-twitch type II MHCs. In the genioglossus muscle, a population of non-IIa non-IIb fast-twitch type II fibers (putatively identified as type IIx MHC fibers) were detected. Hypothyroidism induced significant changes in MHC expression in all muscles studied. In the sternohyoid, type I fibers increased from 6.2 to 16.9%, whereas type IIa fibers increased from 25.9 to 30.7%. Type I fibers in the geniohyoid increased from 1.2 to 12.8%, whereas type IIa fibers increased from 34.1 to 42.7%. The genioglossus showed the smallest relative increase in type I expression but the greatest induction of type IIa MHC. None of the muscles examined demonstrated reinduction of embryonic or neonatal MHC in response to thyroid hormone deficiency. In summary, hypothyroidism alters the MHC profile of pharyngeal dilators in a muscle-specific manner. These changes may play a role in the pathogenesis of obstructive apnea in hypothyroid patients. PMID- 1506367 TI - K+ channel pulmonary vasodilation in fetal lambs: role of endothelium-derived nitric oxide. AB - To define the role and mechanism of action of K+ channels in regulating fetal pulmonary vascular tone, we studied the hemodynamic effects of pinacidil (a K+ channel activator) and glibenclamide (a K+ channel blocker). The effects of pinacidil were compared with those of acetylcholine [an endothelium-derived relaxing factor- (EDRF) dependent pulmonary vasodilator] and 8-bromoguanosine 3',5'-cyclic monophosphate (8-bromo-cGMP, an EDRF-independent pulmonary vasodilator) before and after treatment with N omega-nitro-L-arginine [a competitive inhibitor of an EDRF, endothelium-derived nitric oxide (EDNO), synthesis], or L-arginine (the substrate for the formation of EDNO). In 14 unanesthetized fetal lambs in utero, catheters were inserted into the fetal pulmonary artery, descending aorta, left atrium, and superior vena cava to measure pressures and administer drugs. An ultrasonic flow transducer was placed around the left pulmonary artery to measure flow (QP) continuously. In eight animals, pinacidil, acetylcholine, and 8-bromo-cGMP caused similar acute maximal increases in QP of 128, 137, and 155 ml/min, respectively. After a 60-min infusion of N omega-nitro-L-arginine (2.07 +/- 0.27 mg.kg-1.min-1), the increase in QP caused by acetylcholine and pinacidil was significantly attenuated, by 84 and 68%, respectively, with only a 10% attenuation of the increase in QP caused by 8-bromo-cGMP. In six additional N omega-nitro-L-arginine-pretreated fetal lambs, infusion of L-arginine (32.2 +/- 4.3 mg.kg-1.min-1) restored the vasodilatory effects of acetylcholine and pinacidil. A 20-min infusion of glibenclamide (n = 6; 0.64 +/- 0.07 mg.kg-1.min-1) blocked the vasodilation by pinacidil but not acetylcholine.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1506368 TI - Influence of lung volume and alveolar pressure on reverse pulmonary venous blood flow. AB - We have reported that left atrial blood refluxes through the pulmonary veins to gas-exchanging tissue after pulmonary artery ligation. This reverse pulmonary venous flow (Qrpv) was observed only when lung volume was changed by ventilation. This was believed to drive Qrpv by alternately distending and compressing the alveolar and extra-alveolar vessels. Because lung and pulmonary vascular compliances change with lung volume, we studied the effect of positive end expiratory pressure (PEEP) on the magnitude of Qrpv during constant-volume ventilation. In prone anesthetized goats (n = 8), using the right lung to maintain normal blood gases, we ligated the pulmonary and bronchial arterial inflow to the left lung and ventilated each lung separately. A solution of SF6, an inert gas, was infused into the left atrium. SF6 clearance from the left lung was determined by the Fick principle at 0, 5, 10, and 15 and again at 0 cmH2O PEEP and was used to measure Qrpv. Left atrial pressure remained nearly constant at 20 cmH2O because the increasing levels of PEEP were applied to the left lung only. Qrpv was three- to fourfold greater at 10 and 15 than at 0 cmH2O PEEP. At these higher levels of PEEP, there were greater excursions in alveolar pressure for the same ventilatory volume. We believe that larger excursions in transpulmonary pressure during tidal ventilation at higher levels of PEEP, which compressed alveolar vessels, resulted in the reflux of greater volumes of left atrial blood, through relatively noncompliant extra-alveolar veins into alveolar corner vessels, and more compliant extra-alveolar arteries. PMID- 1506369 TI - Peripheral chemoreceptor modulation of the pulmonary vasculature in the cat. AB - The present study was undertaken to determine whether stimulation of the carotid and aortic bodies (cb and ab) could affect the pulmonary vasculature. Our hypothesis was that each promoted vasodilation and thus could modulate the pulmonary vasoconstrictor response to hypoxia. The experimental design of the first set of experiments took advantage of the facts that 1) the ab, but not the cb, increases its neural output in response to CO, whereas both respond to a decreased arterial PO2 (hypoxic hypoxia, HH) and 2) the aortic nerves in cats are easily transected. Hence, both cb and ab sent neural activity to the brain stem when the intact cat was exposed to 10% O2 in N2. Only the ab sent information during CO hypoxia (COH intact). Only the cb did so during HH in the cat in which the aortic nerves had been transected, removing the aortic body (HH abr); neither ab nor cb did so during COH abr. Fifteen anesthetized paralyzed artificially ventilated cats were fit with catheters in the femoral artery and vein, right and left atria, left ventricle, and pulmonary artery and with an aortic flow probe. In the HH intact and HH abr conditions, there was a significant rise in cardiac output, whereas pulmonary arterial pressure (Ppa) rose initially but then leveled off while cardiac output continued to rise. During the 15-min exposure to HH, pulmonary vascular resistance [PVR = (Ppa - Pla)/cardiac output, where Pla is left atrial pressure] rose initially and then decreased significantly at 2-3 min. In response to COH, PVR showed only a significant decrease. In the second set of experiments, seven cats were instrumented as above and had loops placed in the common carotid arteries for selectively perfusing the cbs. In response to a brief infusion of venous blood mixed with 0.3-0.5 micrograms NaCN, which selectively stimulated only the cb, aortic flow remained relatively constant while heart rate and Ppa - alveolar pressure difference decreased significantly; so also did PVR. These data are consistent with the hypothesis that stimulation of the ab and cb singly or together can provoke a significant pulmonary vasodilation in the anesthetized paralyzed artificially ventilated cat. PMID- 1506370 TI - Effects of age and physical activity status on the speed-aerobic demand relationship of walking. AB - Older adults tend to show lower preferred walking speeds and higher aerobic demands per distance walked than young adults. It has been suggested that a more sedentary life-style contributes to diminished musculoskeletal functioning, which in turn contributes to poorer economy of motion in the aged and sedentary adults. The purpose of this study was to quantify the speed-aerobic demand relationship during walking for old (greater than 65 yr of age) and young adults and to determine whether physical activity status affects this relationship. Aerobic demands for 30 young and 30 old individuals representing sedentary and physically active groups were measured as the subjects performed treadmill walking at seven speeds ranging from 0.67 to 2.01 m/s. All four age/physical activity groups displayed U-shaped speed-aerobic demand curves with minimum gross oxygen consumption per unit distance walked (ml.kg-1.km-1) at 1.34 m/s. A statistically significant age effect on walking aerobic demand was observed, with old subjects showing an 8% higher mean aerobic demand than the young subjects. This age related effect was not associated with shifts in the speed at which aerobic demand was minimized or with the preferred walking speed of older individuals falling on a less economical portion of the speed-aerobic demand curve. Rather, it was speculated that declines in force-generating capacity of muscle in the aged may require recruitment of additional motor units and perhaps an additional proportion of less economical fast twitch muscle fibers to generate necessary forces. Physical activity status had no significant effect on walking aerobic demand.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1506371 TI - Lung tissue behavior during methacholine challenge in rabbits in vivo. AB - Previous studies have shown that lung challenge with smooth muscle agonists increases tissue viscance (Vti), which is the pressure drop between the alveolus and the pleura divided by the flow. Passive inflation also increases Vti. The purpose of the present study was to measure the changes in Vti during positive end-expiratory pressure- (PEEP) induced changes in lung volume and with a concentration-response curve to methacholine (MCh) in rabbits and to compare the effects of induced constriction vs. passive lung inflation on tissue mechanics. Measurements were made in 10 anesthetized open-chest mechanically ventilated New Zealand male rabbits exposed first to increasing levels of PEEP (3-12 cmH2O) and then to increasing concentrations of MCh aerosol (0.5-128 mg/ml). Lung elastance (EL), lung resistance (RL), and Vti were determined by adjusting the equation of motion to tracheal and alveolar pressures during tidal ventilation. Our results show that under baseline conditions, Vti accounted for a major proportion of RL; during both passive lung inflation and MCh challenge this proportion increased progressively. For the same level of change in EL, however, the increase in Vti was larger during MCh challenge than during passive inflation; i.e., the relationship between energy storage and energy dissipation or hysteresivity was dramatically altered. These results are consistent with a MCh-induced change in the intrinsic rheological properties of lung tissues unrelated to lung volume change per se. Lung tissue constriction is one possible explanation. PMID- 1506372 TI - Pulmonary hemodynamics in fetal lambs during development at normal and increased oxygen tension. AB - During the latter third of gestation, the number of resistance vessels in the lungs of the fetal sheep increases by 10-fold even after correction for lung growth. We measured pulmonary arterial pressure and blood flow directly and calculated total pulmonary resistance (pressure divided by flow) in intrauterine fetal lambs at 93-95 days and at 136 days of gestation (term is 145-148 days). In addition, we used a hyperbaric chamber to increase oxygen tension in the fetuses and measured the effect on the pulmonary circulation. When corrected for wet weight of the lungs, pulmonary blood flow did not change with advancing gestation (139 +/- 42 to 103 +/- 45 ml.100 g-1.min-1). Pulmonary arterial pressure increased (42 +/- 5 to 49 +/- 3 mmHg); thus total pulmonary resistance increased with advancing gestation from 0.32 +/- 0.12 to 0.55 +/- 0.21 mmHg.100 g.min.ml-1. If the blood flow is corrected for dry weight of the lungs, neither pulmonary blood flow nor total pulmonary resistance changed with advancing gestation. Increasing oxygen tension increased pulmonary blood flow 10-fold in the more mature fetuses but only 0.2-fold in the less mature fetuses. At the normal low oxygen tension of the fetus, pulmonary blood flow does not increase between these two points of gestation in the fetal lamb despite the increase in vessel density in the lungs. However, during elevated oxygen tension, pulmonary blood flow does increase in proportion to the increase in vessel density. PMID- 1506373 TI - Response of laryngeal mechanoreceptors to high-frequency pressure oscillation. AB - High-frequency pressure oscillations (HFPO) in the upper airway induce arousal, activation of genioglossus muscle, and bronchoconstriction. The present study was designed to determine the response of superior laryngeal nerve afferent fibers to HFPO. In 10 anesthetized dogs spontaneously breathing through a tracheal cannula, the upper airway was converted to a closed system. The activity of thin bundles separated from the peripheral cut end of the superior laryngeal nerve was monitored. Of 104 mechanoreceptors identified, 87 were classified as respiratory modulated and 17 as non-respiratory modulated on the basis of their response to transmural pressure change and muscle activity. The responses of these fibers to HFPO of +/- 2.5 cmH2O at 10, 20, and 30 Hz were determined. Among the respiratory modulated receptors, 86 of 87 increased their activity in response to HFPO. Of the 17 non-respiratory-modulated receptors, 12 receptors showing a random or tonic activity did not respond to HFPO, whereas the 5 that were silent during control condition responded exclusively to HFPO. Our results show that HFPO of similar frequency but much less magnitude than snoring is capable of activating the vast majority of laryngeal mechanoreceptors. Pressure-sensitive respiratory modulated endings appear to mediate the arousal and genioglossal response, whereas non-respiratory-modulated receptors responding to HFPO presumably mediate the bronchoconstrictive response. PMID- 1506374 TI - Effects of capillary red cell density on gas conductance of frog skin. AB - We tested experimentally the hypothesis that decreasing capillary red blood cell (RBC) density (dRBC) reduces the tissue diffusing capacity of frog skin to CO (DtiCO) and O2 (DtiO2). The effects of dRBC on CO2 transport were also assessed. C18O, O2, and CO2 transport between the skin and a cutaneous sample chamber on the belly of anesthetized (halothane) frogs (Rana pipiens) was measured by mass spectrometry, and the cutaneous conductances to C18O (GCO), O2 (GO2), and CO2 (GCO2) were calculated. The dRBC of the planar cutaneous capillary bed was measured by intravital fluorescent video microscopy. DtiCO and DtiO2 were calculated from a modification of the Roughton-Foster equation: 1/G = 1/Dti + 1/(theta RBC.dRBC), where theta RBC values were estimated from literature values. In one group of animals (n = 6), measurements were made before hemodilution (dRBC = 630 +/- 56 cells/mm2), after one hemodilution (dRBC = 349 +/- 50 cells/mm2), and after a second hemodilution (dRBC = 150 +/- 31 cells/mm2). In controls, time had no effect on GCO, GO2, or GCO2 (P greater than 0.42). Before hemodilution, GCO, GO2, and GCO2 were 0.069 +/- 0.010, 0.088 +/- 0.0012, and 1.23 +/- 0.010 nmol.min-1.Torr-1.cm-2, respectively, and lowering dRBC by hemodilution decreased all these parameters (P less than 0.025). The mean slopes of GCO, GO2, and GCO2 vs. dRBC were 6.0 +/- 1.3 x 10(-7), 7.2 +/- 2.3 x 10(-7), and 7.8 +/- 3.0 x 10( 6) nmol.min-1.Torr-1.RBC-1, respectively. Lowering dRBC also decreased DtiCO and DtiO2 (P less than 0.034). DtiCO and DtiO2 were 0.080 +/- 0.012 and 0.096 +/- 0.013 nmol.min-1.Torr-1.cm-2, respectively, before hemodilution. The mean slopes of DtiCO and DtiO2 vs. dRBC were 4.9 +/- 2.1 x 10(-7) and 6.5 +/- 2.8 x 10(-7) nmol.min-1.Torr-1.RBC-1, respectively. Hemodilution had no effect on perfused capillary density (P = 0.38). These results indicate that tissue diffusive conductance is proportional to dRBC. Regulation of dRBC may be an important mechanism modulating diffusive gas transport in tissue. PMID- 1506375 TI - Determination of maximal oxygen consumption in exercising pregnant sheep. AB - Previous work with pregnant ewes has shown that acute bouts of exercise may cause changes in plasma hormone concentrations, blood flow distribution, and maternal and fetal temperatures. However, most of these studies do not quantify the chosen exercise intensity through measurement of oxygen consumption (VO2). Therefore the purpose of this study was to statistically model the VO2 response of pregnant sheep to treadmill (TM) exercise to determine the exercise intensities (% maximal VO2) of previous studies. Ewes with either single (n = 9) or twin (n = 5) fetuses were studied from 100 to 130 days of gestation. After 1-2 wk of TM habituation, maximal VO2 (VO2max) was determined by measurements of VO2 (open flow-through method) and blood lactate concentration. VO2 was measured as a function of TM incline (0, 3, 5, and 7 degree) and speed (0.8-3.4 m/s). VO2max averaged 57 +/- 7 (SD) ml.min-1.kg-1, and peak lactate concentration during exercise averaged 22 +/ 2 mmol/l. The relationship between VO2 (ml.min-1.kg-1) and incline (INC) and speed (SP) [VO2 = 0.70(INC) + 13.95(SP) + 1.07(INC x SP) - 1.18] was linear (r2 = 0.94). Our findings suggest that most previous research used exercise intensities less than 60% VO2max and indicate the need for further research that examines the effect of exercise during pregnancy at levels greater than 60% VO2max. PMID- 1506376 TI - Respiratory muscle blood flow in exercising dogs after pneumonectomy. AB - In three foxhounds after left pneumonectomy, the relationships of ventilatory work and respiratory muscle (RM) blood flow to ventilation (VE) during steady state exercise were examined. VE was measured using a specially constructed respiratory mask and a pneumotach; work of breathing was measured by the esophageal balloon technique. Blood flow to RM was measured by the radionuclide labeled microsphere technique. Lung compliance after pneumonectomy was 55% of that before pneumonectomy; compliance of the thorax was unchanged. O2 uptake (VO2) of RM comprised only 5% of total body VO2 at exercise. At rest, inspiratory muscles received 62% and expiratory muscles 38% of the total O2 delivered to the RM (QO2RM). During exercise, inspiratory muscles received 59% and expiratory muscles 41% of total QO2RM. Blood flow per gram of muscle to the costal diaphragm was significantly higher than that to the crural diaphragm. The diaphragm, parasternals, and posterior cricoarytenoids were the most important inspiratory muscles, and internal intercostals and external obliques were the most important expiratory muscles for exercise. Up to a VE of 120 l/min through one lung, QO2RM constituted only a small fraction of total body VO2 during exercise and maximal vasodilation in the diaphragm was never approached. PMID- 1506377 TI - Immediate diaphragmatic electromyogram responses to imperceptible mechanical loads in conscious humans. AB - We used an esophageal electrode to measure the amplitude and neural inspiratory and expiratory (N TE) timing responses of crural diaphragmatic electrical activity in response to flow-resistive (R) and elastic (E) loads at or below the threshold for conscious detection, applied pseudorandomly to the oral airway of eight normal subjects. We observed a rapid first-breath neural reflex that modified respiratory timing such that N TE lengthened significantly in response to R loads in six of eight subjects and shortened in response to E loading in six of seven subjects. The prolongation of N TE with R loading resulted primarily from lengthening the portion of N TE during which phasic activity in the diaphragm is absent (TE NDIA), whereas E loading shortened N TE mainly by reducing TE NDIA. Most subjects responded to both types of loading by decreasing mean tonic diaphragmatic activity, the average level of muscle activity that exists when no phasic changes are occurring, as well as its variability. The observed timing responses are consistent in direction with optimally adaptive pattern regulation, whereas the modulation of tonic activity may be useful in neural regulation of end-expiratory lung volume. PMID- 1506378 TI - Cardiovascular responses of heart transplant recipients to graded exercise testing. AB - A group of orthotopic heart transplant (OHT, n = 28) and heart surgery (n = 19) patients, with similar ejection fractions and left ventricular end-diastolic pressures, were exercised to symptom-limited maximum to describe differences in cardiovascular and gas exchange responses. Testing was performed at a mean of 3 and 6 mo after surgery, respectively (P less than 0.05). OHT patients have a greater resting systolic and diastolic blood pressure (P less than 0.01) and a significantly greater (P less than 0.01) heart rate (HR) at rest in the supine and standing positions and during minutes 2 through 7 of supine recovery. Peak treadmill time was significantly less (P less than 0.01) in OHT patients. No significant differences were found for systolic blood pressure (SBP) during recovery, peak HR, ventilation, relative O2 uptake (VO2), body weight, ventilatory equivalents for O2 and CO2, O2 pulse, and HR-SBP product (peak HR x peak SBP). Peak pulse pressure, heart rate reserve, total VO2, and absolute VO2 at ventilatory threshold were significantly lower (P less than 0.01) in the OHT patients. We concluded that 1) complete cardiac decentralization is evident, 2) the significantly reduced VO2 at ventilatory threshold should be considered when activities of daily living are prescribed, and 3) SBP response is more appropriate than HR for assessing recovery of the decentralized heart after maximal exercise. PMID- 1506379 TI - Metabolic effects of treadmill exercise training on the diabetic heart. AB - This study determined whether exercise training in rats would prevent the accumulation of lipids and depressed glucose utilization found in hearts from diabetic rats. Diabetes was induced by intravenous streptozotocin (60 mg/kg). Trained diabetic rats were run on a treadmill for 60 min, 27 m/min, 10% grade, 6 days/wk for 10 wk. Training of diabetic rats had no effect on glycemic control but decreased plasma lipids. In vivo myocardial long-chain acylcarnitine, acyl CoA, and high-energy phosphate levels were similar in sedentary control, sedentary diabetic, and trained diabetic groups. The levels of myocardial triacylglycerol were similar in sedentary control and diabetic rats but decreased in trained diabetic rats. Hearts were perfused with buffer containing diabetic concentrations of glucose (22 mM) and palmitate (1.2 mM). D-[U-14C] glucose oxidation rates (14CO2 production) were depressed in hearts from sedentary diabetic rats relative to sedentary control rats. Hearts from trained diabetic rats exhibited increased glucose oxidation relative to those of sedentary diabetic rats, but this improvement was below that of the sedentary control rats. [9,10(-3)H]palmitate oxidation rates (3H2O production) were identical in all three groups. These findings suggest that exercise training resulted in a partial normalization of myocardial glucose utilization in diabetic rats. PMID- 1506380 TI - Pulmonary artery occlusion is sufficient to increase pulmonary vascular permeability in rabbits. AB - Unilateral pulmonary artery obstruction (PAO) for 24-48 h, followed by reperfusion, results in pulmonary edema and lung inflammation. We hypothesized that lung injury actually occurred during the period of PAO but, because of low microvascular pressures during the period of occlusion, was not detected until perfusion was reestablished. To test this hypothesis, we studied 14 rabbits divided into three groups: group I rabbits underwent sham occlusion of the left pulmonary artery for 24 h; group II rabbits underwent PAO but were not reperfused; and group III rabbits were subjected to PAO and then reperfused for 4 h. The fluid filtration coefficient measured during a zone 3 no-flow hydrostatic stress (pulmonary arterial pressure = pulmonary venous pressure, both greater than alveolar pressure) in group I lungs was less than that of lungs in either group II or III [0.52 +/- 0.02 (SE) ml.min-1.cmH2O.100 g wet wt-1 vs. 0.94 +/- 0.11 and 0.86 +/- 0.13 for groups II and III, respectively, P less than 0.05]. The wet-to-dry weight ratio of the left lung measured after the zone 3 stress was applied for 20 min was 6.90 +/- 0.09 in group I rabbits and 9.21 +/- 0.75 and 11.75 +/- 0.44 in groups II and III, respectively (P less than 0.05). Radiolabeled microspheres demonstrated that flow to the left lung was diminished after the period of PAO (38 +/- 4, 9 +/- 5, and 2 +/- 1% of cardiac output in groups I, II, and III, respectively; P less than 0.05 for group I vs. groups II and III).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1506381 TI - Functional residual capacity and ventilation homogeneity in mechanically ventilated small neonates. AB - A modification of a computerized tracer gas (SF6) washout method was designed for serial measurements of functional residual capacity (FRC) and ventilation homogeneity in mechanically ventilated very-low-birth-weight infants with tidal volumes down to 4 ml. The method, which can be used regardless of the inspired O2 concentration, gave accurate and reproducible results in a lung model and good agreement compared with He dilution in rabbits. FRC was measured during 2-4 cmH2O of positive end-expiratory pressure (PEEP) in 15 neonates (700-1,950 g), most of them with mild-to-moderate respiratory distress syndrome. FRC increased with body weight and decreased (P less than 0.05) with increasing O2 requirement. Change to zero end-expiratory pressure caused an immediate decrease in FRC by 29% (P less than 0.01) and gave FRC (ml) = -1.4 + 17 x weight (kg) (r = 0.83). Five minutes after PEEP was discontinued (n = 12), FRC had decreased by a further 16% (P less than 0.01). The washout curves indicated a near-normal ventilation homogeneity not related to changes in PEEP. This was interpreted as evidence against the presence of large volumes of trapped alveolar gas. PMID- 1506382 TI - Instant of vascular occlusion defined with laser-Doppler flowmetry. AB - Derivation of capillary pressure from tracings postarterial (AO) or -venous (VO) occlusion requires back extrapolation to an instant near the time of occlusion. This instant is difficult to identify because of pressure artifacts created by the occlusion maneuver. Theoretically, when the flow in the main artery (or veins) is stopped instantaneously, the flow in the arterioles (or venule) will stop after a short time delay (perhaps less than 100 ms). When flow had stopped in the main artery and in the arteriole, the pressure in the main artery at that instant would equal the pressure in the arterioles. We sought to identify the instant when flow stops in the arterioles and venules after AO and VO, respectively. In an isolated perfused dog left lower lobe preparation flow in the main vessels were monitored with inline flow probes, whereas flow in the microcirculation was monitored with laser-Doppler flow (LDF) probe placed on the lung surface. A sudden decline in arterial flow was detected by the LDF probe after 54 ms, while a sudden decline in venous flow was detected in the venules after 35 ms. These time delays were used as wave transmission time across the arterial and venous trees. Consequently, it was concluded that after AO, flow in the arterioles would stop 54 ms after it had become zero in the main artery, while after VO flow in the venules would stop 35 ms after it had become zero in the main vein. The pressure post-AO and post-VO was read at these instants (54 and 35 ms after flow in the main vessel reached zero).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1506383 TI - Low-frequency pulmonary impedance in rabbits and its response to inhaled methacholine. AB - We assessed pulmonary mechanics in six open-chest rabbits (3 young and 3 adult) by the forced oscillation technique between 0.16 and 10.64 Hz. Under control conditions, pulmonary resistance (RL) decreased markedly between 0.16 and 4 Hz, after which it became reasonably constant. Measurements of alveolar pressure from two alveolar capsules in each rabbit showed that the large decrease of RL with increasing frequency below 4 Hz was due to lung tissue rheology and that tissue resistance was close to zero above 4 Hz. Estimates of resistance and elastance, also obtained by fitting tidal ventilation data at 1 Hz to the equation of the linear single-compartment model, gave values for RL motion that were slightly higher than those obtained by forced oscillations at the same frequency, presumably because of the flow dependence of airways resistance. After treatment with increasing doses of aerosolized methacholine, RL and pulmonary elastance between 0.16 and 1.34 Hz progressively increased, as did the point at which the pulmonary reactance crossed zero (the resonant frequency). The alveolar pressure measurements showed the lung to become increasingly inhomogeneously ventilated in all six animals, whereas in the three younger rabbits lobar atelectasis developed at high methacholine concentrations and the alveolar capsules ceased to communicate with the central airways. We conclude that the low-frequency pulmonary impedance of rabbits exhibits the same qualitative features observed in other species and that it is a sensitive indicator of the changes in pulmonary mechanics occurring during bronchoconstriction. PMID- 1506384 TI - A multipurpose instrument for quantitative intravital microscopy. AB - An in vivo microscope system has been developed that can measure fluorescence emission and/or light absorption at up to five wavelengths in a tissue area of 18 30 microns diam while imaging adjacent microcirculatory vessels with a video system. The system also incorporates a computer-controlled stage and data acquisition system for rapid and repeated measurements from a number of tissue sites. The tissue area monitored for fluorescence or absorption can be defined further by a confocal arrangement of the microscope optics. Tests of the system for NADH fluorescence measurements show good agreement between the fluorescence at 450 nm and NADH concentration in vitro and in skeletal muscle. The instrument can also be used simultaneously for spectrophotometric determination of O2 saturation and hematocrit in microcirculatory vessels. In vitro tests indicate suitable accuracy for such measurements. The open architecture and modular arrangement of the instrument facilitates its use for a variety of simultaneous measurements of parenchymal cell and microcirculatory function. PMID- 1506385 TI - Role of extracellular Ca2+ in diaphragmatic contraction: effects of ouabain, monensin, and ryanodine. AB - The effects of zero extracellular Ca2+ on the contractility of rat diaphragmatic strips in vitro were studied in conjunction with various pharmacological agents known to influence the intracellular Ca2+ concentration: the Na+ ionophore, monensin, and the Na(+)-K+ pump inhibitor, ouabain, which enhance [Ca2+]i, caffeine, which induces Ca2+ release from the sarcoplasmic reticulum (SR), and ryanodine, which prevents Ca2+ retention by the SR. The effect of increasing [Ca2+]i on diaphragmatic contraction was assessed by comparing contractions induced by 120 mM K+ in the small muscle strips before and after the addition of ouabain or monensin. Monensin (20 microM) and ouabain (1-100 microM) augmented contractions up to threefold. Treatment of diaphragm strips with 3 nM ryanodine increased baseline tension 360% above the original resting tension but only if the diaphragm was electrically stimulated concurrently; 100 microM ryanodine induced contracture in quiescent tissue. High K+ contractures were of greater magnitude in the presence of ryanodine compared with control, and relaxation time was prolonged by greater than 200%. Ca(2+)-free conditions ameliorated these actions of ryanodine. Ryanodine reduced contractions induced by 10 mM caffeine and nearly abolished them in Ca(2+)-free solution. The data demonstrate that extracellular Ca2+ is important in certain types of contractile responses of the diaphragm and suggest that the processes necessary to utilize extracellular Ca2+ are present in the diaphragm. PMID- 1506386 TI - Airway narrowing in excised canine lungs measured by high-resolution computed tomography. AB - The exact site of airway narrowing in asthma and chronic obstructive pulmonary disease is unknown. High-resolution computed tomography (HRCT) is a sensitive noninvasive imaging technique that can be used to measure airway dimensions. After determining the optimal computed tomographic parameters using a phantom, we measured lobe volume and airway dimensions of isolated canine lung lobes at a transpulmonary pressure of 25 cmH2O. These measurements were repeated after deflation and administration of aerosolized saline and carbachol (256 mg/ml). Lobe volume decreased with all treatments. The maximal lobar volume change was 26% at 6 cmH2O after carbachol. Average airway lumen area decreased with all treatments. After carbachol, at transpulmonary pressures of 25, 15, 10, 8, and 6 cmH2O, lumen area decreased by 7.3 +/- 4.1, 62.0 +/- 4.9, 77.5 +/- 3.0, 31.9 +/- 9.0, and 95.2 +/- 1.0% (SE), respectively. When the airways were divided into four categories on the basis of initial lumen diameter (less than 2, 2-4, 4-6, and greater than 6 mm), the greatest decreases in luminal area after carbachol were seen in intermediate-sized airways (2-4 mm, 56 +/- 4%; 4-6 mm, 59 +/- 3%). HRCT can be used to make accurate measurements of airway dimensions and airway narrowing in excised lungs. HRCT may allow measurement of airway wall thickness and determination of the site of airway narrowing in asthma. PMID- 1506387 TI - Reversal of hyperdynamic response to continuous endotoxin administration by inhibition of NO synthesis. AB - Septic shock is characterized by an increase in cardiac output and a fall in systemic vascular resistance index and mean arterial pressure. Endotoxin alters the smooth muscle function of blood vessels, probably by means of an increased production of the potent vasodilator nitric oxide (NO). The present study was accomplished to determine how the inhibition of NO synthesis influences cardiovascular performance in an ovine model of hyperdynamic endotoxemia. Endotoxemia was induced in five range ewes (41 +/- 2 kg) by continuous infusion of Escherichia coli endotoxin (LPS, 10 ng.kg-1.min-1) over the entire study period. After 24 h of LPS infusion, cardiac output increased from 5.2 +/- 0.3 to 7.9 +/- 0.6 (SE) 1/min (P less than 0.05) and mean arterial pressure and systemic vascular resistance index fell from 92 +/- 5 to 79 +/- 6 mmHg (P = 0.08) and from 1,473 +/- 173 to 824 +/- 108 dyn.s.cm-5.m2 (P less than 0.05), respectively. The pulmonary shunt fraction increased from 0.23 +/- 0.03 to 0.32 +/- 0.03 (P less than 0.05). The intravenous administration of the NO synthase inhibitor N omega nitro-L-arginine methyl ester (25 mg/kg) 24 h after the start of the LPS infusion changed these values to approximately baseline levels over the subsequent 4 h. Although N omega-nitro-L-arginine methyl ester increased pulmonary arterial pressure and pulmonary vascular resistance (P less than 0.05), right and left ventricular stroke volume index showed no significant changes. It is concluded that NO has a major function in cardiovascular performance in endotoxemia.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1506388 TI - A mathematical model of life-threatening hyperthermia during infancy. AB - A mathematical model was created to test the hypothesis that a partially covered febrile infant may develop potentially lethal temperature elevation. Infants may be at special risk to develop hyperthermia because, unlike older children, infants may not be able to remove blankets in response to temperature elevation. The model compared heat production (MTsk) with heat loss (Qtot). The difference between these terms is the excess energy (E): MTsk - Qtot = E. In most situations the simulated infant transfers heat to the environment as rapidly as it is produced (E less than 0), so hyperthermia does not result. In some situations, heat production exceeds heat loss (E greater than 0), causing progressive warming. The time was calculated for the simulated infant to progress from 41 to 43.4 degrees C (defined as a lethal end point). In certain circumstances, this may occur in less than 90 min. An infant at high risk of hyperthermia may not appear to be covered by a conspicuous excess of insulation (less than or equal to 3.5 cm may be sufficient). In many situations, heat loss is more closely determined by exposed body surface area than by blanket thickness. These findings have important implications for understanding the antecedents of hyperthermia in infants and may help in understanding the role of hyperthermia in certain pediatric illnesses. PMID- 1506389 TI - An animal model of life-threatening hyperthermia during infancy. AB - A mathematical model of heat balance in human infants suggests that it may be possible for severe hyperthermia to develop if an infant is unable to remove his blankets in response to overheating (thermal entrapment). This hypothesis was tested in an animal model of weanling piglets. Ten piglets were warmed in a radiant heater to rectal temperature of 41 degrees C to simulate a fever. Animals in the experimental and control groups were removed from the heater and covered with ordinary infant blankets (to a thickness of approximately 3 cm). Endogenously produced heat caused the animals to warm to 42 degrees C. At this point, the control animals were uncovered. They rapidly cooled to normal body temperature. Animals in the experimental group remained covered until they expired from hyperthermia at 43.9 +/- 0.7 degrees C (SD) after 96 +/- 43 (SD) min. These data show that lethal hyperthermia may result from thermal entrapment. This finding may help clarify the role that hyperthermia may play in illnesses such as hemorrhagic shock and encephalopathy syndrome and some cases of sudden infant death syndrome. PMID- 1506390 TI - Skeletal muscle carnitine metabolism in patients with unilateral peripheral arterial disease. AB - Patients with peripheral arterial disease (PAD) have abnormalities of carnitine metabolism that may contribute to their functional impairment. To test the hypothesis that muscle acylcarnitine generation (intermediates in oxidative metabolism) in patients with PAD provides a marker of the muscle dysfunction, 10 patients with unilateral PAD and 6 age-matched control subjects were studied at rest, and the patients were studied during exercise. At rest, biopsies of the gastrocnemius muscle in the patients' nonsymptomatic leg revealed a normal carnitine pool and lactate content compared with control subjects. In contrast, the patients' diseased leg had higher contents of lactate and long-chain acylcarnitines than controls. The muscle short-chain acylcarnitine content in the patients' diseased leg at rest was inversely correlated with peak exercise performance (r = -0.75, P less than 0.05). With graded treadmill exercise, only patients who exceeded their individual lactate threshold had an increase in muscle short-chain acylcarnitine content in the nonsymptomatic leg, which was identical to the muscle carnitine response in normal subjects. In the patients' diseased leg, muscle short-chain acylcarnitine content increased with exercise from 440 +/- 130 to 900 +/- 200 (SE) nmol/g (P less than 0.05). In contrast to the nonsymptomatic leg, there was no increase in muscle lactate content in the diseased leg with exercise, and the change in muscle carnitine metabolism was correlated with exercise duration (r = 0.82, P less than 0.01) and not with the lactate threshold. We conclude that energy metabolism in ischemic muscle of patients with PAD is characterized by the accumulation of acylcarnitines.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1506391 TI - Effect of fatigue on maximal inspiratory pressure-flow capacity. AB - The inspiratory muscles can be fatigued by repetitive contractions characterized by high force (inspiratory resistive loads) or high velocities of shortening (hyperpnea). The effects of fatigue induced by inspiratory resistive loaded breathing (pressure tasks) or by eucapnic hyperpnea (flow tasks) on maximal inspiratory pressure-flow capacity and rib cage and diaphragm strength were examined in five healthy adult subjects. Tasks consisted of sustaining an assigned breathing frequency, duty cycle, and either a "pressure-time product" of esophageal pressure (for the pressure tasks) or peak inspiratory flow rate (for the flow tasks). Esophageal pressure was measured during maximal inspiratory efforts against a closed glottis (Pesmax), maximal transdiaphragmatic pressure was measured during open-glottis expulsive maneuvers (Pdimax), and maximal inspiratory flow (VImax) was measured during maximal inspiratory efforts with no added external resistance before and after fatiguing pressure and flow tasks. The reduction in Pesmax) with pressure fatigue (-25 +/- 7%) was significantly greater than the change in Pesmax with flow fatigue (-8 +/- 8%, P less than 0.01). In contrast, the reductions in Pdimax (-11 +/- 8%) and VImax (-16 +/- 3%) with flow fatigue were greater than the changes in Pdimax (-0.6 +/- 4%, P less than 0.05) or VImax (-3 +/- 4%, P less than 0.05) with pressure fatigue. We conclude that respiratory muscle performance is dependent not only on the presence of fatigue but whether fatigue was induced by pressure tasks or flow tasks. The specific impairment of Pesmax and not of Pdimax or flow with pressure fatigue may reflect selective fatigue of the rib cage muscles.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1506392 TI - Cardiopulmonary adaptations to pneumonectomy in dogs. I. Maximal exercise performance. AB - Maximal exercise performance was evaluated in four adult foxhounds after right pneumonectomy (removal of 58% of lung) and compared with that in seven sham operated control dogs 6 mo after surgery. Maximal O2 uptake (ml O2.min-1.kg-1) was 142.9 +/- 1.9 in the sham group and 123.0 +/- 3.8 in the pneumonectomy group, a reduction of 14% (P less than 0.001). Maximal stroke volume (ml/kg) was 2.59 +/ 0.10 in the sham group and 1.99 +/- 0.05 in the pneumonectomy group, a reduction of 23% (P less than 0.005). Lung diffusing capacity (DL(CO)) (ml.min-1.Torr-1.kg 1) reached 2.27 +/- 0.08 in the combined lungs of the sham group and 1.67 +/- 0.07 in the remaining lung of the pneumonectomy group (P less than 0.001). In the pneumonectomy group, DL(CO) of the left lung was 76% greater than that in the left lung of controls. Blood lactate concentration and hematocrit were significantly higher at exercise in the pneumonectomy group. We conclude that, in dogs after resection of 58% of lung, O2 uptake, cardiac output, stroke volume, and DL(CO) at maximal exercise were restricted. However, the magnitude of overall impairment was surprisingly small, indicating a remarkable ability to compensate for the loss of one lung. This compensation was achieved through the recruitment of reserves in DL(CO) in the remaining lung, the development of exercise-induced polycythemia, and the maintenance of a relatively large stroke volume in the face of an increased pulmonary vascular resistance. PMID- 1506393 TI - Human tolerance to heat strain during exercise: influence of hydration. AB - This study determined whether 1) exhaustion from heat strain occurs at the same body temperatures during exercise in the heat when subjects are euhydrated as when they are hypohydrated, 2) aerobic fitness influences the body temperature at which exhaustion from heat strain occurs, and 3) curves could be developed to estimate exhaustion rates at a given level of physiological strain. Seventeen heat-acclimated men [maximal oxygen uptake (VO2max) from 45 to 65 ml.kg-1.min-1] attempted two heat stress tests (HSTs): one when euhydrated and one when hypohydrated by 8% of total body water. The HSTs consisted of 180 min of rest and treadmill walking (45% VO2max) in a hot-dry (ambient temperature 49 degrees C, relative humidity 20%) environment. The required evaporative cooling (Ereq) exceeded the maximal evaporative cooling capacity of the environment (Emax); thus thermal equilibrium could not be achieved and 27 of 34 HSTs ended by exhaustion from heat strain. Our findings concerning exhaustion from heat strain are 1) hypohydration reduced the core temperature that could be tolerated; 2) aerobic fitness, per se, did not influence the magnitude of heat strain that could be tolerated; 3) curves can be developed to estimate exhaustion rates for a given level of physiological strain; and 4) exhaustion was rarely associated with a core temperature up to 38 degrees C, and it always occurred before a temperature of 40 degrees C was achieved. These findings are applicable to heat-acclimated individuals performing moderate-intensity exercise under conditions where Ereq approximates or exceeds Emax and who have high skin temperatures. PMID- 1506394 TI - A signal-averaging technique for the analysis of human muscle sympathetic nerve activity. AB - We present a signal-averaging technique for analysis of human muscle sympathetic nerve activity (SNA). Nerve traffic was averaged by coupling signal acquisition to electrocardiographic R waves. The amplitude of the averaged waveform was multiplied by the number of R waves sampled to provide a measure of SNA in arbitrary units. This was compared with SNA measured by manual digitization of hard-copy records. In nine volunteers, SNA was increased or decreased with stepwise infusions of nitroprusside or phenylephrine: there were 10 5-min periods of data in each subject. Across all subjects, the correlation between manual and signal-averaged measures of SNA was excellent during both nitroprusside (r = 0.98) and phenylephrine infusions (r = 0.91) and the slopes of the regression lines were near unity. In three periods of data collection, electrical artifacts were added randomly at frequencies of 0.5 and 0.07 Hz during playback of the signal into the computer. Signal-averaged estimates of SNA were unaffected by artifacts. This technique provides reliable observer-independent measures of SNA. PMID- 1506395 TI - Contraction-activated glucose uptake is normal in insulin-resistant muscle of the obese Zucker rat. AB - The rates of muscle glucose uptake of lean and obese Zucker rats were assessed via hindlimb perfusion under basal conditions (no insulin), in the presence of a maximal insulin concentration (10 mU/ml), and after electrically stimulated muscle contraction in the absence of insulin. The perfusate contained 28 mM glucose and 7.5 microCi/mmol of 2-deoxy-D-[3H-(G)]glucose. Glucose uptake rates in the soleus (slow-twitch oxidative fibers), red gastrocnemius (fast-twitch oxidative-glycolytic fibers), and white gastrocnemius (fast-twitch glycolytic fibers) under basal conditions and after electrically stimulated muscle contraction were not significantly different between the lean and obese rats. However, the rate of glucose uptake during insulin stimulation was significantly lower for obese than for lean rats in all three fiber types. Significant correlations were found for insulin-stimulated glucose uptake and glucose transporter protein isoform (GLUT-4) content of soleus, red gastrocnemius, and white gastrocnemius of lean (r = 0.79) and obese (r = 0.65) rats. In contrast, the relationships between contraction-stimulated glucose uptake and muscle GLUT-4 content of lean and obese rats were negligible because of inordinately low contraction-stimulated glucose uptakes by the solei. These results suggest that maximal skeletal muscle glucose uptake of obese Zucker rats is resistant to stimulation by insulin but not to contractile activity. In addition, the relationship between contraction-stimulated glucose uptake and GLUT-4 content appears to be fiber-type specific. PMID- 1506396 TI - Plasma Met-enkephalin and catecholamine responses to intense exercise in humans. AB - Native and cryptic Met-enkephalin and catecholamines are coreleased in response to stress. However, it is not known whether Met-enkephalin and catecholamines exhibit concurrent temporal relationships in response to exercise. The purpose of this investigation was to examine the corelease of catecholamines and Met enkephalin in endurance-trained (n = 6) and untrained (n = 6) male subjects during a 6-min bout of exercise: 4 min at 70% of maximal O2 uptake (VO2max) followed by 2 min at 120% VO2max. Peak catecholamine levels were found at 1 min of recovery. In trained subjects, native Met-enkephalin peaked during exercise at 70% VO2max, declined during exercise at 120% VO2max, and returned to basal levels by 1 min of recovery. In the untrained subjects, native Met-enkephalin peaked at 120% VO2max (6 min) and returned to baseline by 5 min of recovery. In both groups, cryptic Met-enkephalin peaked at 70% VO2max and returned to basal levels during exercise at 120% VO2max. These data demonstrate that during exercise there is a temporal dissociation in plasma levels of Met-enkephalin and catecholamines. PMID- 1506397 TI - Effect of leukopenia on pulmonary hypertension after heparin-protamine in pigs. AB - Heparin neutralization by protamine after cardiac surgery and cardiopulmonary bypass may be associated with complement activation, transient leukopenia, thromboxane A2 release, and severe pulmonary hypertension. The role of leukocytes in the heparin-protamine reaction was studied in leukopenic pigs (n = 9) and a control group (n = 8). Leukopenia was induced by pretreatment with cyclophosphamide (30 mg.kg-1.day-1) for 6-7 days. During general anesthesia and after catheterization, baseline recordings of hemodynamics were performed and blood samples were withdrawn. Heparin (250 IU/kg) was injected and measurements were repeated after 10 min. Protamine sulfate (100 mg) was then infused over 2 min and measurements were performed after 2, 5, and 15 min. Prostanoid concentrations were measured by radioimmunoassays. In additional in vitro experiments, the release of thromboxane B2 from washed platelets and leukocytes after heparin-protamine stimulation was measured. Pretreatment with cyclophosphamide reduced leukocyte counts by 95.5% and the number of neutrophils by greater than 99.9%. Protamine infusion increased mean pulmonary arterial pressure by 74 and 46% and pulmonary vascular resistance by 185 and 384% in control and leukopenic animals, respectively. Thromboxane B2 concentrations increased in both groups. Stimulation by heparin, protamine, or heparin and protamine in sequence did not induce any thromboxane A2 release from washed blood cells. It is concluded that leukocytes do not contribute to pulmonary hypertension after heparin-protamine. PMID- 1506398 TI - Pulmonary vascular protein sieving capability after exposure to high vascular pressures. AB - We evaluated the ability of the canine in situ left lower lobe (LLL) vasculature to sieve endogenous plasma proteins of various molecular radii (34-124 A) after LLL arterial pressure had been transiently elevated to 23.8 +/- 0.9 (control group, n = 5) or 92.3 +/- 1.4 (SE) Torr (high-pressure group, n = 9) by restricting LLL venous outflow under conditions of constant flow. After LLL flow was returned to natural perfusion, left atrial pressure was elevated in step increments, and LLL lymph and blood samples were collected until filtration independent lymph-to-plasma protein concentration ratios (CL/CP) were obtained. The osmotic reflection coefficients (sigma d) for total proteins and seven protein fractions (separated by gradient gel electrophoresis) were calculated. The average total protein sigma d of the high-pressure group [0.51 +/- 0.06 (SE)] was significantly lower than that of the control group (0.68 +/- 0.03). Several LLLs of the high-pressure group, however, exhibited normal sigma d's. Protein fraction CL/CP's decreased with increasing molecular radius in both groups, but the CL/CP-molecular radius relationship was displaced upward in the high-pressure group. Pore analysis suggested that the decreases in sigma d could be explained by increases in the fractional flow through a large-pore system. PMID- 1506399 TI - Reduction in myotendinous junction surface area of rats subjected to 4-day spaceflight. AB - The surface area of myotendinous junctions (MTJs), expressed relative to the cross-sectional area of myofibrils attached to them, was determined using established morphometric techniques in which the digitlike processes of the cell at MTJs are modeled as circular paraboloids. The relative area, called the folding factor, was measured for six rats after a 4-day spaceflight and six control rats maintained in a vivarium under otherwise identical conditions. Spaceflight resulted in a significant reduction in relative MTJ surface area, from 19.7 +/- 2.3 (SD) in control animals to 13.3 +/- 2.5 for animals after spaceflight. Furthermore, space animals displayed increased numbers of fibroblasts enriched in rough endoplasmic reticulum near the MTJ, a greater number of ribosomes and mitochondria within muscle at the MTJ, and increased occurrence of lesions in the connective tissue near the MTJ. The results indicate that spaceflight, possibly through the removal of gravity-associated loading from muscle, causes a modification in MTJ structure and may result in injuries at MTJs after return to normal loading. PMID- 1506400 TI - Hypertrophic response to unilateral concentric isokinetic resistance training. AB - The purposes of this study were to 1) determine the effect of concentric isokinetic training on strength and cross-sectional area (CSA) of selected extensor and flexor muscles of the forearm and leg, 2) examine the potential for preferential hypertrophy of individual muscles within a muscle group, 3) identify the location (proximal, middle, or distal level) of hypertrophy within an individual muscle, and 4) determine the effect of unilateral concentric isokinetic training on strength and hypertrophy of the contralateral limbs. Thirteen untrained male college students [mean age 25.1 +/- 6.1 (SD) yr] volunteered to perform six sets of 10 repetitions of extension and flexion of the nondominant limbs three times per week for 8 wk, using a Cybex II isokinetic dynamometer. Pretraining and posttraining peak torque and muscle CSA measurements for both the dominant and nondominant limbs were determined utilizing a Cybex II isokinetic dynamometer and magnetic resonance imaging scanner, respectively. The results indicated significant (P less than 0.0008) hypertrophy in all trained muscle groups as well as preferential hypertrophy of individual muscles and at specific levels. None of the muscles of the contralateral limbs increased significantly in CSA. In addition, significant (P less than 0.0008) increases in peak torque occurred for trained forearm extension and flexion as well as trained leg flexion. There were no significant increases in peak torque, however, for trained leg extension or for any movement in the contralateral limbs. These data suggest that concentric isokinetic training results in significant strength and hypertrophic responses in the trained limbs. PMID- 1506401 TI - Aminophylline increases submaximum power but not intrinsic velocity of shortening of frog muscle. AB - We hypothesized that methylxanthines, such as aminophylline, increase the power developed by submaximally activated frog skeletal muscles by increasing the force developed at any given velocity of shortening. Frog semitendinosus muscles were excised and tested at 20 degrees C in oxygenated control and aminophylline Ringer solutions. Force-velocity relationships were determined and power was calculated from muscles stimulated at frequencies of 80 and 300 Hz. The 300-Hz frequency of stimulation produced a maximum rate of force development. In 50 and 500 microM aminophylline, twitch force increased by 25 +/- 12 and 75 +/- 13%, respectively. Aminophylline did not affect maximum isometric force generation or the shortening velocity at any relative load. At 80-Hz stimulation and in the presence of 500 microM aminophylline, power increased by an average of 11% at 10 of 14 relative loads. At maximum frequencies of stimulation, aminophylline had no effect on any measured parameter. We conclude that aminophylline increases the power developed by submaximally activated frog muscles through an increase in the force generated particularly at the lower velocities of shortening. PMID- 1506402 TI - Human muscle fatigue after glycogen depletion: a 31P magnetic resonance study. AB - To differentiate the effects of high energy phosphates, pH, and [H2PO4-] on skeletal muscle fatigue, intracellular acidosis during handgrip exercise was attenuated by prolonged submaximal exercise. Healthy human subjects (n = 6) performed 5-min bouts of maximal rhythmic handgrip (RHG) before (CONTROL) and after prolonged (60-min) handgrip exercise (ATTEN-EX) designed to attenuate lactic acidosis in active muscle by partially depleting muscle glycogen. Concentrations of free intracellular phosphocreatine ([PCr]), adenosine triphosphate ([ATP]), and orthophosphate ([P(i)]) and pH were measured by 31P nuclear magnetic resonance spectroscopy and used to calculate adenosine diphosphate [ADP], [H2PO4-], and [HPO4(2-)]. Handgrip force output was measured with a dynamometer, and fatigue was determined by loss of maximal contractile force. After ATTEN-EX, the normal exercise-induced muscle acidosis was reduced. At peak CONTROL RHG, pH fell to 6.3 +/- 0.1 (SE) and muscle fatigue was correlated with [PCr] (r = 0.83), [P(i)] (r = 0.82), and [H2PO4-] (r = 0.81); [ADP] was 22.0 +/- 5.7 mumol/kg. At peak RHG after ATTEN-EX, pH was 6.9 +/- 0.1 and [ADP] was 116.1 +/- 18.2 mumol/kg, although [PCr] and [P(i)] were not different from CONTROL RHG (P greater than 0.05). After ATTEN-EX, fatigue correlated most closely with [ADP] (r = 0.84). The data indicate that skeletal muscle fatigue 1) is multifactorial, 2) can occur without decreased pH or increased [H2PO4-], and 3) is correlated with [ADP] after exercise-induced glycogen depletion. PMID- 1506403 TI - Effects of hyperphosphatemia on diaphragmatic strength and endurance. AB - Effects of an infusion of Na2HPO4 on diaphragm strength, endurance, and magnitude of recovery were evaluated in in situ canine diaphragm strips. Results showed no effect on maximal isometric tetanic tension. Twitch tension and tension in the low- (10-Hz) frequency range were significantly increased (P less than 0.01). Time to fatigue (endurance) increased by 38 +/- 4.5% in the group that received phosphorus compared with its control and decreased by 18.5 +/- 2.5% in the group that received dextrose compared with its control (P less than 0.005). Recovery from fatigue was also significantly improved after the phosphorus infusion. Serum ATP and 2,3-diphosphoglycerate levels were unchanged throughout the experiment. The results of this study support the notion that hyperphosphatemia improves diaphragmatic endurance and recovery from fatigue. The mechanisms involved may in part be due to the phosphate-buffering effects, which limit the extent of the muscle intracellular acidosis produced with fatigue. PMID- 1506404 TI - Pores of Kohn are filled in normal lungs: low-temperature scanning electron microscopy. AB - Interalveolar pores of Kohn, small uniform-sized epithelium-lined openings in alveolar walls of normal lung, have historically been demonstrated with electron microscopic techniques that remove water. We show these pores to be present but almost invariably filled with material when water and surfactant are preserved in frozen hydrated lung examined with low-temperature scanning electron microscopy. In the normal mouse, 16 open empty pores per alveolus were found in instillation fixed dried lung vs. less than 1 per alveolus in frozen hydrated lungs (P less than 0.001). In the normal rat, 13 pores were seen per alveolus in instillation fixed dried lung vs. less than 1 per alveolus in frozen hydrated lungs (P less than 0.001). We suggest that pores of Kohn 1) function primarily as conduits for interalveolar movement of alveolar liquid, surfactant components, and macrophages, 2) provide distributed sites for tubular myelin storage without increasing gas diffusion pathway thickness in the alveolar subphase itself, and 3) do not function as pathways for collateral ventilation during normal breathing in the absence of atelectasis or obstruction. PMID- 1506405 TI - Characteristics of spontaneous and evoked motility in the isolated perfused porcine duodenum. AB - The aims of the study were to evaluate characteristics of spontaneous motility and of the ascending excitatory peristaltic reflex (AEPR) and intraluminal cross sectional area in the isolated perfused porcine duodenum. The parameters were measured by an intraluminal catheter by use of the perfused side-hole technique and impedance planimetry. Respiratory parameters such as pH and oxygen consumption and the arterial perfusion pressure were monitored and did not vary significantly throughout the study time. Spontaneous motility was intense at the beginning but declined and disappeared within 45-90 min. It was abolished by atropine, epinephrine, and UK-14,304 (an alpha 2-adrenoceptor agonist). Secondary motility was evoked by intraluminal balloon distensions by raising the balloon pressure to 1.5 kPa for 1-min periods. Reproducible results regarding the AEPR, external balloon diameters to elicit the AEPR, and intraluminal cross-sectional area were obtained. The order of potency (pD2 values) for inhibition of the AEPR was the selective M3-receptor antagonist 4-DAMP greater than atropine greater than the selective M2-receptor antagonist AFDX-116 greater than the selective M1 receptor antagonist pirenzepine greater than hexamethonium. 4-DAMP was 16 and 29 times more potent than AFDX-116 (P less than 0.02) and pirenzepine (P less than 0.02). None of the drugs altered the intraluminal cross-sectional area during the balloon distensions. The model provides the opportunity for physiological and pharmacological studies of duodenal motility and duodenal cross-sectional area devoid of extrinsic neural and endocrine effects. The abolishment of the AEPR by atropine is caused by blockade of the M3-receptor in the porcine duodenum. PMID- 1506406 TI - Medullary CO2 chemoreceptor neuron identification by c-fos immunocytochemistry. AB - In a search for CO2 chemoreceptor neurons in the brain stem, we used immunocytochemistry to monitor the expression of neuronal c-fos, a marker of increased activity, after 1 h of exposure to CO2 in five groups of Sprague-Dawley rats (294 +/- 20 g): five air breathing controls, three breathing 10% CO2, three breathing 13% CO2, three breathing 15% CO2, and three breathing 15% CO2 and treated with morphine (10 mg/kg sc). After exposure the rats were anesthetized with pentobarbital sodium and perfused intracardially with 4% paraformaldehyde. The brain stem was removed and cryoprotected, and then 50-microns frozen sections were cut and immunostained for the fos protein. Brain stem fos-immunoreactive neurons were plotted and counted in the superficial 0.5 mm of the ventral medullary surface. Thirteen to 15% CO2 evoked fos-like immunoreactivity (FLI) in 321 +/- 146 neurons/rat. Significant CO2-induced labeling was confined within the superficial 150 microns: 67% of identified cells were less than 50 microns below the surface, greater than 90% between 1.0 and 3.0 mm from the midline, and approximately 60% in the rostral half of the medulla. Thirteen to 15% CO2 also evoked FLI in the area of the nucleus tractus solitarius but not in other medullary regions. Morphine (10 mg/kg sc) did not suppress high CO2-evoked FLI in either the ventral medullary surface or the nucleus tractus solitarius, although it eliminated excitement and hyperventilation. We suggest that respiratory CO2 chemoreceptor neurons can be identified in rats by their expression of c-fos after 1 h of hypercapnia.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1506407 TI - Nigericin forms highly stable complexes with lithium and cesium. AB - Nigericin is a monocarboxylic polyether molecule described as a mobile K+ ionophore unable to transport Li+ and Cs+ across natural or artificial membranes. This paper shows that the ion carrier molecule forms complexes of equivalent energy demands with Li+, Cs+, Na+, Rb+, and K+. This is in accordance with the similar values of the complex stability constants obtained from nigericin with the five alkali metal cations assayed. On the other hand, nigericin-alkali metal cation binding isotherms show faster rates for Li+ and Cs+ than for Na+, K+, and Rb+, in conditions where the carboxylic proton does not dissociate. Furthermore, proton NMR spectra of nigericin-Li+ and nigericin-Cs+ complexes show wide broadenings, suggesting strong cation interaction with the ionophore; in contrast, the complexes with Na+, K+, and Rb+ show only clear-cut chemical shifts. These latter results support the view that nigericin forms highly stable complexes with Li+ and Cs+ and contribute to the explanation for the inability of this ionophore to transport the former cations in conditions where it catalyzes a fast transport of K+ greater than Rb+ greater than Na+. PMID- 1506408 TI - Hexokinase receptors: preferential enzyme binding in normal cells to nonmitochondrial sites and in transformed cells to mitochondrial sites. AB - Hexokinase plays an important role in normal glucose-utilizing tissues like brain and kidney, and an even more important role in highly malignant cancer cells where it is markedly overexpressed. In both cell types, normal and transformed, a significant portion of the total hexokinase activity is bound to particulate material that sediments upon differential centrifugation with the crude "mitochondrial" fraction. In the case of brain, particulate binding may constitute most of the total hexokinase activity of the cell, and in highly malignant tumor cells as much as 80 percent of the total. When a variety of techniques are rigorously applied to better define the particulate location of hexokinase within the crude "mitochondrial fraction," a striking difference is observed between the distribution of hexokinase in normal and transformed cells. Significantly, particulate hexokinase found in rat brain, kidney, or liver consistently distributes with nonmitochondrial membrane markers whereas the particulate hexokinase of highly glycolytic hepatoma cells distributes with outer mitochondrial membrane markers. These studies indicate that within normal tissues hexokinase binds preferentially to nonmitochondrial receptor sites but upon transformation of such cells to yield poorly differentiated, highly malignant tumors, the overexpressed enzyme binds preferentially to outer mitochondrial membrane receptors. These studies, taken together with the well-known observation that, once solubilized, the particulate hexokinase from a normal tissue can bind to isolated mitochondria, are consistent with the presence in normal tissues of at least two different types of particulate receptors for hexokinase with different subcellular locations. A model which explains this unique transformation-dependent shift in the intracellular location of hexokinase is proposed. PMID- 1506409 TI - High-conductance pathways in mitochondrial membranes. AB - The outer and inner membranes of mitochondria have recently been studied with the patch clamp technique. What has emerged is still an ill-defined picture for either membrane, primarily for the wide range of conductances found. Interestingly, however, a few conductances (in the range of 10-80 pS) seem to be ubiquitously distributed. Parallel studies in situ and in reconstituted systems have allowed the assignment to distinct membrane locations of some conductances, whose physiological role is, however, not yet elucidated. PMID- 1506410 TI - Cytoskeletal elements are required for the formation and maturation of autophagic vacuoles. AB - We evaluated the role of cytoskeletal elements in the degradation of endogenous proteins via autophagy using biochemical and morphological techniques. In the absence of exogenous amino acids, degradation of endogenous proteins was enhanced in cultured normal rat kidney cells. This enhanced degradative state was accompanied by a 4-fold increase in the occurrence of autophagic vacuoles. In the presence of drugs that induce the depolymerization of microfilaments (cytochalasins B and D) or microtubules (nocodazole), protein degradation was not enhanced in nutrient-deprived cells. Although these drugs had similar inhibitory effects on the protein degradation, their effect on autophagy differed. Cytochalasins B and D interfered with the formation of the autophagosome. In cells treated with these drugs, the fractional volume represented by autophagic vacuoles was not substantially increased despite nutrient depletion. On the contrary, nocodazole appeared to have no effect on the formation of autophagosomes. Instead, this drug suppressed the delivery of hydrolytic enzymes, thereby resulting in an accumulation of acidic autophagic vacuoles containing undegraded cellular components. PMID- 1506411 TI - Transforming growth factor-beta 1 mediated alterations in ribonucleotide reductase gene expression in BALB/c 3T3 fibroblasts. AB - Transforming growth factor-beta 1 (TGF-beta 1) stimulated DNA synthesis (3-fold) in BALBc/3T3 fibroblasts following 24 hours of growth factor exposure. Since ribonucleotide reductase is important for the coordination of DNA synthesis and cell proliferation, we investigated the hypothesis that cells like BALB/c 3T3, which are TGF-beta 1 responsive, would exhibit modifications in expression of the gene for ribonucleotide reductase following growth factor treatment. We observed 2.6, 4.1, and 4.8-fold increases in ribonucleotide reductase activity following TGF-beta 1 exposure for 6, 12, and 24 hours, respectively. Increased ribonucleotide reductase R2 gene expression (3, 3.7, and 4.5-fold) and R1 gene expression (2,2.5, and 2.6-fold) were observed following 6, 12, and 24 hours of TGF-beta 1 treatment, respectively. Western blots indicated 2.2, 3.1, and 4.1 fold increases in protein R2 levels at 6, 12, and 24 hours exposure to TGF-beta 1, whereas 2.6 and 3.3-fold elevations in R1 protein levels were observed at 12 and 24 hours post-TGF-beta 1 exposure. These TGF-beta 1 mediated modifications in ribonucleotide reductase gene expression occurred, in part, prior to any detectable changes in the rate of DNA synthesis, demonstrating alterations in the normal regulation of ribonucleotide reductase. Furthermore, these alterations could be markedly reduced by prolonged pretreatment with 12-O tetradecanoylphorbol-13-acetate (R2 gene expression increased by only 1.3, 1.5 and 2.3-fold after 6, 12, and 24 hours of TGF-beta 1 treatment, respectively), suggesting a role for a protein kinase C pathway in the TGF-beta 1 regulated changes in ribonucleotide reductase gene expression. These results indicate for the first time that TGF-beta 1 can regulate the expression of the two genes for ribonucleotide reductase in BALB/c 3T3 fibroblasts, and suggest that regulation of these genes plays an important role in critical events involved in growth factor modulation of normal and transformed cell proliferation. PMID- 1506412 TI - Protein kinase C remains functionally active during TPA induced neuronal differentiation of SH-SY5Y human neuroblastoma cells. AB - SH-SY5Y human neuroblastoma cells can be induced to differentiate into a neuronal phenotype by treatment with 12-O-tetradecanoylphorbol-13-acetate (TPA). In other cell systems, TPA treatment frequently leads to down-regulation of protein kinase C (PKC). However, we now report that TPA-treated and non-treated SH-SY5Y cells express PKC-alpha, but not PKC-beta and PKC-gamma, mRNA. Furthermore, only a slight down-regulation of the PKC-alpha protein could be seen during prolonged treatment with 16 nM TPA, the concentration giving optimal differentiation. In contrast, a higher concentration of TPA (1.6 microM) results in a poor neuronal differentiation and a complete down-regulation of PKC-alpha. PKC-alpha was rapidly translocated to the particulate fraction and remained membrane bound for at least 4 days during treatment with 16 nM TPA. In such cells a sustained increased level of the phosphorylated form of a 80,000 Dalton PKC-substrate was found. In addition to this sustained augmented phosphorylation, administration of fresh TPA at day 4 caused a small but reproducible further increased level of phosphorylated substrate. When the PKC activity was measured by the histone phosphorylation assay a substantial fraction of the initial enzyme activity could still be detected after 4 days of TPA treatment. Taken together, the data demonstrate that PKC remains functionally active during TPA induced differentiation of SH-SY5Y cells, which may suggest a continuous role for the enzyme during the differentiation process. PMID- 1506413 TI - Brefeldin A, thapsigargin, and AIF4- stimulate the accumulation of GRP78 mRNA in a cycloheximide dependent manner, whilst induction by hypoxia is independent of protein synthesis. AB - The glucose regulated proteins (GRPs) are major structural components of the endoplasmic reticulum (ER) and are involved in the import, folding, and processing of ER proteins. Expression of the glucose regulated proteins (GRP78 and GRP94) is greatly increased after cells are exposed to stress agents (including A23187 and tunicamycin) which inhibit ER function. Here, we demonstrate that three novel inhibitors of ER function, thapsigargin (which inhibits the ER Ca(2+)-ATPase), brefeldin A (an inhibitor of vesicle transport between the ER and Golgi) and AIF4-, (which inhibits trimeric G-proteins), can increase the expression of both GRP78 and 94. The common characteristic shared by activators of GRP expression is that they disrupt some function of the ER. The increased levels of GRPs may be a response to the accumulation of aberrant proteins in the ER or they may be increased in response to structural/functional damage to the ER. The increased accumulation of GRP78 mRNA after exposure of cells to either thapsigargin, brefeldin A, AIF4-, A23187, or tunicamycin can be blocked by pre-incubation in cycloheximide. In contrast, accumulation of GRPs after exposure to hypoxia was independent of cycloheximide. In addition, the protein kinase inhibitor genistein blocked the thapsigargin induced accumulation of GRP78 mRNA, whereas the protein phosphatase inhibitor okadaic acid caused increased accumulation of GRP78 mRNA. The data indicates that there are at least 2 mechanisms for induced expression of GRPs, one of which involves a phosphorylation step and requires new protein synthesis (e.g., thapsigargin, A23187) and one which is independent of both these steps (hypoxia). PMID- 1506414 TI - EGF receptor regulation in normal mouse mammary gland. AB - Estrogen (E), progesterone (P), and epidermal growth factor (EGF) are known to regulate growth and development of the normal mammary gland, and it is possible that EGF may interact with E and/or P. Estrogen (ER), progesterone (PR), and EGF receptors (EGF-R) have been detected in both mammary epithelial and stromal cells, and the relative roles of the various cells types in hormone-dependent growth regulation are not known. The present studies were undertaken to determine if E and/or P influence EGF action by exerting a regulatory effect on EGF-R levels and which cell types are affected. The comparative effects of ovariectomy and hormone treatments on EGF-R levels were examined in immature, pubertal 5-week old and sexually mature 10-week-old female mice. EGF-R were characterized as a single class of high affinity sites and EGF-R concentration was 2-fold higher in glands of 5-week-old mice. Ovariectomy had no significant effect on EGF-R concentration in either age group, and treatment with E and/or P had no effect on EGF-R levels in either epithelial or stromal cells in 5-week-old mice. In contrast, E+P treatment caused a 2-fold increase in receptor concentration in 10 week-old mice in the mammary epithelium. Thus it appears that the developmental state of the gland may determine the nature and extent of the interaction of of EGF, E, and P. PMID- 1506415 TI - Transforming growth factor-beta 1 rapidly induces Hsp70 and Hsp90 molecular chaperones in cultured chicken embryo cells. AB - In this report we show that: (1) molecular chaperones in the heat shock protein (hsp) family are a new class of cellular proteins induced by Transforming Growth Factor-beta 1 (TGF beta), a cytokine present in serum, (2) rapid induction of Hsc70 precedes a general increase in protein synthesis and may be a preparatory event, (3) TGF beta is a potent regulator of overall protein synthesis in chicken embryo cells (CEC), and (4) isoforms of Hsp90 with different biochemical properties exist, raising the possibility that they may have different functions. TGF beta can substitute for serum in stimulating synthesis of members of the Hsp90 and Hsp70 families of stress proteins, whereas other cytokines, including PDGF, FGF, and EGF, were not effective nor did they enhance the stimulatory effect of TGF beta on the hsp's. Analysis of the induction of hsp's using one- and two-dimensional polyacrylamide gel electrophoresis indicated that members of the Hsp70 family of molecular chaperones were induced rapidly by TGF beta, reaching maximum rates of accumulation by 5 hours of treatment. Total protein synthesis increased more slowly, undergoing an approximately twofold increase in 24 hours. Using a modified protocol for two-dimensional gel electrophoresis, the Hsp90 protein family was separated into four isoelectric forms, two of which were phosphorylated (Hsp90-2 and -4). These phosphorylated isoforms turned over faster than the unphosphorylated forms of Hsp90. All four isoforms were heat inducible, but only Hsp90-2 and -3 were induced rapidly by TGF beta, again within 5 hours of treatment. The effects of serum on these protein families were similar to those of TGF beta, suggesting that this cytokine may be the serum component primarily responsible for up-regulating members of the Hsp90 and Hsp70 families. We hypothesize that cells rapidly increase their chaperoning capacity for newly synthesized polypeptides in preparation for an increase in the rate of synthesis of proteins up-regulated by TGF beta. PMID- 1506416 TI - C-fos expression is hypersensitive to serum-stimulation in cultured cystic kidney cells from the C57BL/6J-cpk mouse. AB - Cystic kidneys of the C57BL/6J-cpk murine model of polycystic kidney disease show a marked overexpression of the proto-oncogenes c-fos, c-myc, and c-Ki-ras, consistent with an increased rate of cell proliferation and an altered state of differentiation. To determine if cystic cells have increased responsiveness to stimulation with mitogenic agents, quiescent primary cultures from normal and cystic cpk kidneys were treated with fetal bovine serum (FBS), 8-bromo-cAMP (cAMP), or epidermal growth factor (EGF). The level of c-fos induction following stimulation by FBS was found to be dramatically higher in cystic cells than in normal cells; whereas induction by cAMP or EGF was essentially the same in both cell types and much less than that seen in FBS-stimulated cells. To determine if this serum hypersensitivity reflects an increased proliferative state in vivo, c fos induction was examined in cultures derived from normal kidneys stimulated to regenerate by folic acid-induced acute renal injury. As with cystic kidneys, the folic acid-injured kidneys showed increased c-fos responsiveness to FBS in cell culture. These experiments suggest that cystic and regenerating kidneys have an altered phenotypic state in vivo that is manifested in cell culture by serum hypersensitivity. However, whereas the folic acid-injured kidneys ultimately reestablish normal kidney function, cystic kidneys further progress to renal failure, suggesting that cystic epithelial cells are locked in this altered state of differentiation. PMID- 1506417 TI - Cytokines involved in monocyte mediated tumor cell death and growth inhibition in serum-free medium. AB - In a serum-free culture system, the release of TNF, lI-1, lI-6, IFN-alpha, and IFN-beta during interaction of elutriated human monocytes (MO) with human tumor cells (TC) was studied by ELISA-technique. Contributions of these cytokines to inhibition of TC-growth and to induction of TC-death by supernatants (SU) gained from such MO/TC-interaction cultures were investigated using affinity chromatography for removal of individual cytokines. Although the TC used are relatively insensitive to recombinant human TNF, withdrawal of TNF causes 50% to 75% reduction of SU-induced TC-death rates, suggesting that susceptibility to TNF is raised during MO/TC-interaction by the other cytokines. Individual removal of other cytokines does not cause reduction of SU-mediated TC-death. However, combined withdrawal of lI-1 and IFN-alpha/beta causes in 2 of 4 TC-lines significant reduction of TC-death. Combined removal of TNF, IFN-alpha/beta, lI-1, and lI-6 leads to complete prevention of SU-mediated growth inhibitory and lytic effects, suggesting that besides these cytokines other signals are not involved significantly. SU-effects can be mimicked by appropriate combinations of authentic cytokines. The response of TC to SU- or cytokine-exposure is strikingly dependent on TC-density, leading at subconfluent TC-density exclusively to inhibition of growth and at postconfluent TC-density to induction of cell death. The principal effect of SU or cytokine combinations in this context seems to be the activation of growth inhibitory signal transduction pathways leading to TC death in postconfluent TC-populations exclusively if growth stimulatory pathways are activated at the same time. Mouse L cells do not follow this reaction pattern: Their death is exclusively dependent on the presence of TNF in SU and they die upon SU-exposure at postconfluent as well as at subconfluent cell density. PMID- 1506418 TI - Independent regulation of prostaglandin production and the stress response in human fibroblasts. AB - The stress, or heat shock response of eukaryotic cells is characterized by dramatic changes in the metabolism of responding cells, most notably the increased synthesis of a group of proteins known as heat shock proteins. In this study, we examined the relationship of prostaglandin synthesis/release to the stress response. Stress protein synthesis was induced with sodium arsenite, and prostaglandin E2 and prostacyclin (measured as 6-keto PGF1 alpha) levels were determined by enzyme immunoassay. The stress response was monitored by the incorporation of [35S]methionine and separation of protein by one-dimensional sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Prostaglandin synthesis and the stress response were both induced by sodium arsenite. However, aspirin, a cyclooxygenase inhibitor, inhibited arsenite-induced prostaglandin synthesis but did not inhibit stress protein synthesis. Conversely, the calcium ionophore A23187 also stimulated prostaglandin synthesis, but did not induce the stress response. The results of this study indicate that sodium arsenite, a stress response inducer, stimulates prostaglandin production, but this appears to be a correlative rather than causative occurrence in the stress response. Determination of the cytotoxicity of arsenite indicated a high correlation of stimulation of prostaglandin release with cytotoxicity. PMID- 1506419 TI - Relationship between culture conditions and the dependency on mitochondrial function of mammalian cell proliferation. AB - In cultured mammalian cells, the relationship was investigated between mitochondrial function and proliferation under various culture conditions. Continuous inhibition of the expression of the mitochondrial genome was used to reduce the activity of enzymes involved in oxidative phosphorylation by 50% at every cell division. Under these conditions, culturing in relatively poor media resulted in arrest of the proliferation of most cell lines after 1 cell division. This was preceded by decreasing levels of ATP and increasing levels of ADP, suggesting that the ATP-generating capacity of the cells was limiting. Culturing in richer media led to arrest of the proliferation after 5 to 6 divisions, but accumulation of ADP was not observed. Addition of pyruvate to rich culture media and, at least for 1 cell line, increasing the CO2 levels, completely prevented proliferation arrest. Inability to synthesise metabolic precursors via mitochondrial intermediary metabolism probably explains growth arrest of cells cultured in rich media. Pyruvate and CO2 were, however, without effect on the proliferation arrest of cells cultured in relatively poor media. Therefore, pyruvate dependency for growth of cells without functional mitochondria holds true only under culture conditions where the ATP-generating capacity of the cells is not limiting. PMID- 1506420 TI - Reversible G1 arrest of a human lung epithelial cell line by staurosporine. AB - Staurosporine, a microbial-derived protein kinase inhibitor, reversibly blocked non-synchronized, replicating cultures of the human lung epithelial cell line EKVX in the G1 phase of cell cycle and inhibited DNA synthesis and cell replication. The mechanism of this cell-cycle arrest in EKVX cells by staurosporine was likely due to inhibition of protein kinase C (PKC) because: 1) dose-dependent inhibition of DNA synthesis occurred at levels of staurosporine that inhibit phosphorylation of PKC substrate, 2) inhibition of DNA synthesis was also seen after treatment with another PKC inhibitor H7, but not by the chemically similar HA1004, which has a relative inhibitory specificity for cAMP dependent protein kinase, and 3) the DNA synthesis was not inhibited by specific tyrosine kinase inhibitors Genistein and Lavendustin A at concentrations that inhibit tyrosine kinase activity. Removal of staurosporine from cell culture media resulted in a rebound in PKC activity and synchronized DNA synthesis in EKVX cultures. The reversibility of the inhibition was noted even after 5 days of treatment with staurosporine, and DNA synthesis remained synchronized for at least two rounds of cell replication after removal of staurosporine. Flow cytometric analysis confirmed that more than 90% of the cell population was blocked in the G1 phase after cells were treated with staurosporine for 24 h. Agents such as staurosporine may be useful for synchronizing cell populations to study cell-cycle specific biochemical events important for the regulation of cell replication in the EKVX cell line. PMID- 1506421 TI - Colcemid and the mitotic cycle. PMID- 1506423 TI - Effects of vinblastine, podophyllotoxin and nocodazole on mitotic spindles. Implications for the role of microtubule dynamics in mitosis. AB - Inhibition of mitosis by many drugs that bind to tubulin has been attributed to depolymerization of microtubules. However, we found previously that low concentrations of vinblastine and vincristine blocked mitosis in HeLa cells with little or no depolymerization of spindle microtubules, and spindles appeared morphologically normal or nearly normal. In the present study, we characterized the effects of vinblastine, podophyllotoxin and nocodazole over broad concentration ranges on mitotic spindle organization in HeLa cells. These three drugs are known to affect the dynamics of microtubule polymerization in vitro and to depolymerize microtubules in cells. We wanted to probe further whether mitotic inhibition by these drugs is brought about by a more subtle effect on the microtubules than net microtubule depolymerization. We compared the effects of vinblastine, podophyllotoxin and nocodazole on the organization of spindle microtubules, chromosomes and centrosomes, and on the total mass of microtubules. Spindle organization was examined by immunofluorescence microscopy, and microtubule polymer mass was assayed on isolated cytoskeletons by a quantitative enzyme-linked immunoadsorbence assay for tubulin. As the drug concentration was increased, the organization of mitotic spindles changed in the same way with all three drugs. The changes were associated with mitotic arrest, but were not necessarily accompanied by net microtubule depolymerization. With podophyllotoxin, mitotic arrest was accompanied by microtubule depolymerization. In contrast, with vinblastine and nocodazole, mitotic arrest occurred in the presence of a full complement of spindle microtubules. All three drugs induced a nearly identical rearrangement of spindle microtubules, an increasingly aberrant organization of metaphase chromosomes, and fragmentation of centrosomes. The data suggest that these anti-mitotic drugs block mitosis primarily by inhibiting the dynamics of spindle microtubules rather than by simply depolymerizing the microtubules. PMID- 1506422 TI - DNA-binding domain of RCC1 protein is not essential for coupling mitosis with DNA replication. AB - The RCC1 protein that is required for coupling mitosis with the S phase has a DNA binding domain in the N-terminal region outside the repeat. We found that RCC1 protein without any DNA-binding activity complemented the tsBN2 mutation with the same efficiency as that of intact RCC1 protein. In ts+ transformants of tsBN2 cells transfected with the RCC1 cDNA lacking the DNA-binding domain, an endogenous RCC1 disappeared at 39.5 degrees C, and the deleted RCC1 protein encoded by the transfected cDNA was found in the cytoplasm, but a significant amount of it was also found in the nuclei. This deleted RCC1 protein was eluted from the nuclei with the same concentration of NaCl and DNase I as was used for the intact RCC1 protein in BHK21 cells. Furthermore, the deleted RCC1 protein co migrated with the nucleosome fraction on sucrose density gradient analysis. These results indicate that the RCC1 protein binds chromatin with the aid of other unknown protein(s). Thus, the DNA-binding domain of RCC1 protein is not essential for coupling between the S and M phases, but was shown instead to function as a nuclear translocation signal. PMID- 1506424 TI - Subcellular imaging of calcium exchange in cultured cells with ion microscopy. AB - Calcium to calcium exchange between intracellular and extracellular pools has been imaged directly in individual cells using stable 44Ca (98.78% enrichment) in the nutrient medium and an isotopic imaging technique, ion microscopy. Observations were made by imaging mass 40 to determine the native intracellular calcium (40Ca), and mass 44 to localize the 44Ca from the extracellular medium that exchanged with cellular calcium. LLC-PK1 porcine kidney epithelial cells were exposed to the nutrient medium with 1.87 mM stable 44Ca for 0, 1, 2, 5, 8, 20, 60 and 90 min, and cryogenically prepared prior to ion microscopic analysis. The cell nucleus, the Golgi region and the remaining cell cytoplasm could be spatially resolved to within about 0.5 microns using the ion microscope. On the basis of the kinetics of 40Ca to 44Ca exchange it was observed that all three compartments had a rapidly exchanging pool of calcium, which took about 2 min to exchange. A moderately rapidly exchanging pool of calcium was identified between 2 and 20 min of calcium exchange. The cells had exchanged about 50% of their total internal calcium with the external calcium in less than 20 min. The remaining 50% of the cellular calcium could be classified as a slowly exchanging pool. Isotopic images of 39K and 23Na were recorded along with 40Ca and 44Ca images to assess the health status of the cell. Isotopic imaging has the unique ability to distinguish intracellular calcium from the extracellular calcium that enters cells and has enormous potential for studies of calcium transport under physiological and pathological conditions. PMID- 1506425 TI - Differential expression of the VLA family of integrins along the crypt-villus axis in the human small intestine. AB - Regulation of epithelial cell proliferation, migration and differentiation under physiological conditions remains poorly understood. Interaction of the cells with their underlying basement membrane through integrins, a specific subset of cell surface binding proteins, is one potential mechanism. In the present work, I examined this hypothesis by investigating the distribution of a variety of epithelial basement membrane proteins and the expression of the members of the VLA family of integrins in the adult intestinal epithelium. Indeed, this rapidly renewing simple epithelium contains within its functional unit, the crypt-villus axis, essentially two distinct cell populations: the proliferative and undifferentiated crypt cells and the mature enterocytes on the villus. Although immunolocalization of basement membrane molecules revealed that laminin, type IV collagen and heparan sulfate proteoglycan are distributed homogeneously all along the crypt-villus axis, other non-exclusive basement membrane components were found differentially expressed. Tenascin was concentrated at the base of both villus and lower crypt cells while cellular fibronectin was mostly detected in association with the crypt cells. Moreover, VLA beta 1 as well as 5 of the 6 VLA alpha subunits tested were expressed by intestinal epithelial cells under specific patterns of staining. The beta 1 and alpha 6 subunits were strongly detected at the base of all enterocytes while alpha 5, also detected all along the crypt-villus axis, was weaker and consistently appeared with a punctated/interrupted pattern. On the other hand, the VLA alpha 1, alpha 2 and alpha 3 were expressed at the basolateral domains of enterocytes under distinctive crypt-villus gradients. The alpha 1 subunit was detected at the base of all epithelial cells but lateral staining was only observed in differentiating cells (middle and upper crypt). Finally, in most specimens, alpha 2 and alpha 3 displayed strictly complementary staining patterns for the lower crypt region (alpha 2+, alpha 3-) and the upper crypt-to-villus region (alpha 2-, alpha 3+). Taken together, these data emphasize that proliferation, migration and differentiation in the normal state are susceptible to various influences including compositional changes in the basement membrane and differential expression of receptors for these components. PMID- 1506426 TI - Collagen-induced rapid morphogenesis of human mammary epithelial cells: the role of the alpha 2 beta 1 integrin. AB - The cell line MTSV1-7, originally derived by immortalizing mammary epithelial cells cultured from human milk was able to form three-dimensional structures in collagen gel. We have now found that these cells, cultured as a monolayer, are able to undergo rapid morphogenesis forming ridges and balls around collagen fibres, when soluble collagen type I is added to the medium. Monoclonal antibodies to the alpha 2 (P1E6) and beta 1- (mAB13) subunits of VLA-2, but not to the alpha 3-subunit (P1B5) of VLA-3, could block this collagen-induced rapid morphogenesis (CIRM). The effect of the antibodies on cell attachment, spreading, and migration on collagen gels was analyzed to identify alpha 2 beta 1 dependent steps which might be involved in CIRM. The results suggest that while other proteins, besides alpha 2 beta 1, are also involved in cell attachment and migration, cell spreading was specifically blocked by antibodies to the VLA-2, but not to the VLA-3 integrin. The results demonstrate that the alpha 2 beta 1 integrin plays a crucial role in the collagen-induced morphogenesis of human mammary epithelial cells and implicate the process of VLA-2-dependent cell spreading as an important step in this morphogenesis. PMID- 1506427 TI - Antagonistic effects of TGF-beta 1 and MSF on fibroblast migration and hyaluronic acid synthesis. Possible implications for dermal wound healing. AB - The migration of adult skin fibroblasts into three-dimensional collagen gel matrices is differentially affected by cell density, with subconfluent cells displaying a significantly elevated level of migration compared to confluent ones. Fetal fibroblasts differ from adult cells in that they display an elevated level of migration at both subconfluent and confluent cell densities. We have previously reported that this difference in behaviour results from the secretion by fetal fibroblasts of a 'migration stimulating factor' (MSF) which is not made by their normal adult counterparts, and that MSF appears to act by stimulating the synthesis of hyaluronic acid (HA). Data presented in this communication indicate that (a) MSF specifically stimulates the synthesis of high molecular weight species of HA, (b) TGF-beta 1 inhibits the elevated migration of adult fibroblasts plated at subconfluent cell density, (c) under these conditions, TGF beta 1 induces a parallel decrease in the synthesis of high molecular weight HA and increase in the synthesis of low molecular weight HA, (d) TGF-beta 1 is a potent antagonist of MSF, effectively blocking its stimulation of cell migration and synthesis of high molecular weight HA, and (e) the inhibition of fibroblast migration by TGF-beta 1 does not appear to be a chemotactic response dependent upon the existence of a concentration gradient of the cytokine. Our observations regarding the inhibitory effects of TGF-beta 1 on fibroblast migration into 3D collagen gels stand in marked contrast to various published reports indicating that this cytokine stimulates the migration of human skin fibroblasts through the pores of polycarbonate filters as used in modified Boyden chamber assays; this discrepancy underscores the importance of the substratum in modulating cellular response to cytokines. Our results are discussed in terms of the possible combined contribution of MSF and TGF-beta 1 to wound healing. PMID- 1506428 TI - Cell cycle modification during the transitions between meiotic M-phases in mouse oocytes. AB - When metaphase II-arrested mouse oocytes (M II) are activated very soon after ovulation, they respond abortively by second polar body extrusion followed by another metaphase arrest (metaphase III, M III; Kubiak, 1989). The M II/M III transition resembles the natural transition between the first and second meiotic metaphases (M I/M II). We observed that a similar sequence of events takes place during these two transitions: after anaphase, a polar body is extruded, the microtubules of the midbody disappear rapidly and a new metaphase spindle forms. The MPM-2 monoclonal antibody (which reacts with phosphorylated proteins associated with the centrosome during M-phase) stains discrete foci of peri centriolar material only in metaphase arrested oocytes; during both transitional periods, a diffuse staining is observed, suggesting that these centrosomal proteins are dephosphorylated, as in a normal interphase. However, the chromosomes always remain condensed and an interphase network of microtubules is never observed during the transitional periods. Incorporation of 32P into proteins increases specifically during the transitional periods. Pulse-chase experiments, after labeling of the oocytes in M phase with 32P, showed that a 62 kDa phosphoprotein band disappears at the time of polar body extrusion. Histone H1 kinase activity (which reflects the activity of the maturation promoting factor) drops during both transitional periods to the level characteristic of interphase and then increases when the new spindle forms. Both the M I/M II and M II/M III transitions require protein synthesis as demonstrated by the effect of puromycin. These results suggest that the two M-phase/M-phase transitions are probably driven by the same molecular mechanism. PMID- 1506429 TI - Expression and function of ras proto-oncogene proteins in human sperm cells. AB - The presence and role of c-ras proteins were investigated in mature human sperm cells. The v-H-ras monoclonal antibody (mAb) against the c-ras protein, p21, reacted specifically with the acrosomal region of methanol-fixed as well as unfixed-live capacitated and non-capacitated human sperm cell in the indirect immunofluorescence technique. The v-H-ras mAb predominantly recognized c-ras protein of 21 kDa on the Western blot of lithium diiodosalicylate (LIS) solubilized human sperm preparation. The incubation of sperm cells with v-H-ras mAb affected the sperm cell function in the human sperm penetration assay. The antibody significantly reduced the acrosome reaction and release of acrosin activity from the sperm cells. There was no effect of the mAb on percentage motility, although the mAb significantly affected various motility characteristics such as linearity, amplitude of lateral head displacement (ALH) and beat frequency, the motility parameters involved in the hyperactivation phenomenon of sperm cells leading to capacitation and acrosome reaction. These results suggest that the c-ras or c-ras-like proteins are present in mature sperm cell and may have a role in capacitation and/or acrosome reaction of human sperm cell. PMID- 1506430 TI - Constitutive secretion of a bacterial enzyme by polarized epithelial cells. AB - The constitutive (or default) pathway for protein secretion was investigated in two epithelial cells, Madin-Darby canine kidney (MDCK) and human colonic adenocarcinoma (Caco-2), using a bacterial enzyme. The choice of a bacterial protein was based on the requirement to identify a protein devoid of sorting signals. The sorting of a bacterial endoglucanase derived from Clostridium thermocellum, endoglucanase E, from stably transfected MDCK and Caco-2 cells was examined. The choice of a bacterial endoglucanase for these studies has advantages of simple, sensitive and quantitative detection, while higher eukaryotic cells do not express endoglucanase activity. Both cell lines secreted a 50 kDa form of the bacterial protein, while smaller intracellular forms were also observed. In polarized layers of MDCK cells the endoglucanase was secreted into both membrane domains in the ratio 62% apical and 38% basolateral. In Caco-2 cells secretion was predominantly, 70%, through the basolateral membrane. These results define the constitutive pathway for protein secretion in these two model epithelial cells. PMID- 1506431 TI - Effect of caffeine on intracellular transport of Semliki Forest virus membrane glycoproteins. AB - The effect of caffeine on the intracellular transport of Semliki Forest virus (SFV) membrane glycoproteins was studied in baby hamster kidney (BHK) cells. The movement of the proteins was affected at two steps in the exocytic pathway. The exit of the proteins from the endoplasmic reticulum (ER) was inhibited by 10 mM caffeine at 20 degrees C, a temperature that normally allows transport to the Golgi complex. At higher temperatures (28 degrees C and 37 degrees C) in the presence of 10 mM caffeine exit from the ER occurred, but the proteins accumulated at intracellular membrane elements. Immunofluorescence localization, endoglycosidase-H analysis, and analysis of the proteolytical cleavage of the p62 precursor protein suggested that transport in the presence of 10 mM caffeine was arrested at the membranes between the trans-Golgi and the plasma membrane. PMID- 1506432 TI - Origins of the parasitophorous vacuole membrane of the malaria parasite, Plasmodium falciparum, in human red blood cells. AB - We have attempted to determine whether the parasitophorous vacuole membrane, in which the malaria parasite (merozoite) encapsulates itself when it enters a red blood cell, is derived from the host cell plasma membrane, as the appearance of the invasion process in the electron microscope has been taken to suggest, or from lipid material stored in the merozoite. We have incorporated into the red cell membrane a haptenic phospholipid, phosphatidylethanolamine, containing an NBD (N-(7-nitrobenz-2-oxa-1,3-diazol-4-yl)) group, substituted in the acyl chain, and allowed it to translocate into the inner bilayer leaflet. After invasion of these labelled cells by the parasite, Plasmodium falciparum, immuno-gold electron microscopy was used to follow the distribution of the labelled lipid; this was found to be overwhelmingly in favour of the host cell membrane relative to the parasitophorous vacuole. Merozoites of P. knowlesi were allowed to attach irreversibly to red cells without invasion, using the method of pretreatment with cytochalasin. The region of contact between the merozoite and the host cell membrane was in all cases devoid of the labelled phosphatidylethanolamine. These results lead us to infer that the parasitophorous vacuole membrane is derived wholly or partly from lipid preexisting in the merozoite. PMID- 1506433 TI - Syringe loading introduces macromolecules into living mammalian cell cytosol. AB - We describe a simple, efficient, gentle and inexpensive technique for the introduction of normally impermeant macromolecules into the cytosol of living mammalian cells growing in suspension or attached to the culturing substratum. Loading is achieved by the production of transient, survivable plasma membrane disruptions as cells are passed back and forth through a standard syringe needle or similar narrow orifice. The loading volume required, which contains cells and the macromolecule to be loaded, can be as little as 5 microliters, thus minimizing the use of valuable reagents. In addition, we report that the surfactant molecule, Pluronic F-68, is capable of altering the physical properties of the plasma membrane in such a way as to increase loading efficiency and the long-term survivability of cells loaded by this and other mechanically based cell-loading techniques. PMID- 1506434 TI - Structure of the cortical cytoskeleton in mammalian outer hair cells. AB - The cortical cytoskeletal lattice in outer hair cells is a two-dimensional actin based structure, which can be labelled with rhodamine/phalloidin and disrupted by the enzyme deoxyribonuclease I. Structural information from thin sectioned, freeze-etched and negatively stained preparations shows that it is based upon two types of filament that form a cross-linked lattice of circumferential filaments. The cross-links are 70-80 nm long. Measurements of the spacing between circumferential filaments suggest that the lattice is stiffer circumferentially than it is longitudinally. Analysis of the orientation of circumferential filaments shows that it is composed of discrete domains of up to 10 microns 2. Relative movements between domains could allow substantial changes of cell shape without disrupting the unit structure of the lattice, thus allowing the cell cortex to retain its elastic responses to high-frequency deformations. PMID- 1506435 TI - Characterization of the enterocyte-like brush border cytoskeleton of the C2BBe clones of the human intestinal cell line, Caco-2. AB - The brush border (BB) of the enterocyte is a well-studied example of the actin based cytoskeleton. We describe here a cell culture model that expresses a faithful representation of the in vivo structure. Two clones (C2BBe 1 and 2) isolated from the cell line Caco-2 (derived from a human colonic adenocarcinoma) formed a polarized monolayer with an apical BB morphologically comparable to that of the human colon. BBs could be isolated by standard methods and contained the microvillar proteins villin, fimbrin, sucrase-isomaltase and BB myosin I, and the terminal web proteins fodrin and myosin II. The immunolocalization of these proteins in confluent, filter-grown monolayers was determined by laser scanning confocal microscopy; patterns of distribution comparable to those in human enterocytes were observed. Sedimentation analysis of cell homogenates derived from C2BBe cells and human colonic epithelial cells demonstrated similar patterns of fractionation of BB proteins; the physical association of those proteins, as determined by extraction from the BB, was also comparable between the two cell types. Like enterocytes of the human intestine, C2BBe cells expressed multiple myosin I immunogens reactive with a head domain-specific monoclonal antibody raised against avian BB myosin I, one of which co-migrated with the approximately 110 kilodalton (kDa) heavy chain of human BB myosin I. In addition, the C2BBe cells express a pair of higher molecular mass immunogens (130 and 140 kDa). These myosin I immunogens all exhibit ATP-dependent association with the C2BBe cytoskeleton. Although the higher molecular mass immunogens were detected in several other human intestinal lines examined, including the parent Caco-2 line, none of these other lines expressed detectable levels of the 110 kDa immunogen, which is presumed to be the heavy chain of human BB myosin I. PMID- 1506436 TI - Stage-specific tyrosine phosphorylation of actin in Dictyostelium discoideum cells. AB - A 45 kDa protein in Dictyostelium discoideum cells that was recognized by a phosphotyrosine-specific antibody was identified by its binding activity to DNase I and its 2D-electrophoretic behavior as actin. The reactivity of actin with the antibody was transiently enhanced for about 30 minutes shortly after starving cells were reintroduced into nutrient medium. This effect indicates a modification of actin that is regulated under physiological conditions. A similar effect was obtained when growing cells were treated with phenylarsine oxide (PAO), an inhibitor of phosphotyrosine phosphatases. This effect was reversed and the cells fully recovered upon addition of the PAO antagonist 2,3 dimercaptopropanol. Starved cells did not show this enhancement of antibody labelling, which indicates that the response to PAO depends on the developmental stage. Phosphorylated amino acid residues were identified after in vivo labelling with [32P]phosphate in the presence of PAO. Part of the radioactivity in the actin band was recovered as phosphotyrosine, another part as phosphoserine. PAO caused the cells to form elongated blebs, to round up and finally to become immobilized. Fluorescence labelling with phalloidin of cells that were fixed at different times of PAO treatment revealed a progressive decrease in the staining for actin filaments and showed that these alterations in cytoskeleton organization were readily reversible, in accordance with the reversal of tyrosine phosphorylation at actin. PMID- 1506437 TI - The localization of myosin I and myosin II in Acanthamoeba by fluorescence microscopy. AB - We used several fixation protocols and a panel of monoclonal antibodies to re examine the localization of myosin I and myosin II in Acanthamoeba. Two monoclonal antibodies that bind to the head of myosin II stain a range of particles in the cytoplasm. The smallest and most numerous cytoplasmic particles are about the same size and intensity as myosin II minifilaments and are distributed throughout the endoplasm. The largest particles stain like myosin II thick filaments and are concentrated in the cleavage furrow of dividing cells and in the tail of locomoting cells. Five different monoclonal antibodies that bind to the myosin II tail also stain cytoplasmic particles but with a limited range of intensity. None of the myosin II monoclonal antibodies stains the contractile vacuole or plasma membrane. Two monoclonal antibodies to myosin I gave punctate cytoplasmic staining that did not correspond clearly to any of the phase-dense particles in the cytoplasm. In many, but not all, locomoting cells, the myosin I staining was concentrated at the leading edge. Both myosin I antibodies stained a single cytoplasmic vacuole of variable size that was presumed to be the contractile vacuole. The antibody that binds myosin IA but not myosin IB stained novel intercellular contacts and the antibody that binds both myosin IA and myosin IB stained the plasma membrane, especially the tips of filopodia. PMID- 1506438 TI - Formation of highly organized skeletal muscle fibers in vitro. Comparison with muscle development in vivo. AB - Two methods were developed in which long-term cultures of quail skeletal muscle were established so that all of the muscle fibers develop in a highly oriented manner. The muscle fibers became spontaneously and vigorously contractile and established strong connections with the extracellular matrix at their ends that closely duplicate the structure of the myotendinous junction. A continuous basal lamina was formed around each muscle fiber that contained type IV collagen, laminin and heparan sulfate proteoglycan. With one of the methods, an extensive extracellular matrix developed around each muscle fiber that was highly organized with the formation of a distinctive epimysium, perimysium and endomysium. Analysis of the cultures by both methods for different isoforms of myosin showed expression of an adult form of myosin by some of the muscle cells. The results therefore demonstrate that muscle development in the present culture systems proceeds extensively for several weeks. It will now be possible to investigate directly the structure of the connections between muscle fibers and the extracellular matrix. PMID- 1506439 TI - Neuroreceptor quantitation in vivo by the steady-state principle using constant infusion or bolus injection of radioactive tracers. AB - The approaches hitherto used for measuring the kinetic constants Kd and Bmax of neuroreceptors in vivo all violate the steady state of the system. This complicates the kinetic analysis as approximations must be made, introducing errors of unknown magnitude. The present study presents the theory for designing experiments in which the steady state is preserved. It is based on maintaining a constant degree of receptor binding (occupancy) throughout the experiment. This is achieved by administering by prolonged intravenous infusion the non radioactive ligand one wishes to study. The fraction of receptors sites not occupied by the "cold" ligand is measured by using trace amounts of a radioactive ligand binding to the same receptor. A minimum of two studies at different occupanies must be performed. In this presentation it is proposed to make the second study at essentially zero receptor occupancy by administering the tracer alone. The pair of tracer studies, the one without and the other with infusion of cold ligand, allows calculation of the cold ligand's equilibrium dissociation constant Kd. In the special case when tracer and cold ligands are chemically identical, then Bmax can also be calculated. Two different modes of tracer administration can be used. If the tracer is also infused at a constant rate for a long time, then the occupancy of receptor sites by the cold ligand can be calculated by measuring the equilibrium tracer concentrations in brain and plasma. If the tracer is administered as an intravenous bolus injection, then the area under the brain and plasma radioactivity curves or compartmental analysis must be used.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1506440 TI - Repeated negative DC deflections in rat cortex following middle cerebral artery occlusion are abolished by MK-801: effect on volume of ischemic injury. AB - Following permanent occlusion of the left middle cerebral artery (MCA) in rats, electrophysiological and hemodynamic characteristics of the periinfarct border zone were investigated in sham-operated (n = 6), untreated (n = 6), and MK-801 treated (3.0 mg/kg; n = 6) animals. For this purpose, direct current potential (DC), EEG, and blood flow (laser-Doppler flowmetry) were recorded from the cortex in the periphery of the MCA territory. In sham-operated rats, a single negative cortical DC deflection was observed after electrocoagulation of the cortex, whereas in untreated MCA-occluded animals, three to eight transient DC deflections were monitored during the initial 3 h of ischemia. The duration of these cortical DC shifts gradually increased from 1.2 +/- 0.3 to 3.7 +/- 2.7 min (mean +/- SD; p less than 0.05) during this time. In animals treated intraperitoneally with MK-801 (3.0 mg/kg) immediately after MCA occlusion, the number of cortical DC shifts significantly declined to one to three deflections (p less than 0.005). The EEG of the treated animals revealed low-amplitude burst suppression activity. In the untreated and treated experimental group, the reduction of cortical blood flow amounted to 69 +/- 25 and 49 +/- 13% of control, respectively. Despite the more pronounced cortical oligemia, MK-801 treatment resulted in a significant decrease of the volume of the ischemically injured tissue from 108 +/- 38.5 (untreated group) to 58 +/- 11.5 (p less than 0.05) mm3. Our results suggest that repetitive cortical DC deflections in the periinfarct border zone contribute to the expansion of ischemic brain infarcts. PMID- 1506441 TI - Elevated lactate and alkalosis in chronic human brain infarction observed by 1H and 31P MR spectroscopic imaging. AB - The goal of this study was to investigate lactate and pH distributions in subacutely and chronically infarcted human brains. Magnetic resonance spectroscopic imaging (MRSI) was used to map spatial distributions of 1H and 31P metabolites in 11 nonhemorrhagic subacute to chronic cerebral infarction patients and 11 controls. All six infarcts containing lactate were alkalotic (pHi = 7.20 +/- 0.04 vs. 7.05 +/- 0.01 contralateral, p less than 0.01). This finding of elevated lactate and alkalosis in chronic infarctions does not support the presence of chronic ischemia; however, it is consistent with the presence of phagocytic cells, gliosis, altered buffering mechanisms, and/or luxury perfusion. Total 1H and 31P metabolites were markedly reduced (about 50% on average) in subacute and chronic brain infarctions (p less than 0.01), and N-acetyl aspartate (NAA) was reduced more (approximately 75%) than other metabolites (p less than 0.01). Because NAA is localized in neurons, selective NAA reduction is consistent with pathological findings of a greater loss of neurons than glial cells in chronic infarctions. PMID- 1506442 TI - Increased cerebral blood flow in anemic patients on long-term hemodialytic treatment. AB - CBF was measured in 15 patients on chronic hemodialytic treatment. CBF was measured with xenon-133 inhalation using single photon emission tomography. In addition, computerized tomography (CT) and a neurological examination were done prior to hemodialysis. Mean CBF was 66.2 +/- 17.3 (SD) ml 100 g-1 min-1, which was significantly higher (t-test, p less than 0.05) than for an age-matched control group (54.7 +/- 10.2 ml 100 g-1 min-1). However, the hematocrit for the patients was considerably lower, 0.30 +/- 0.07, as compared to 0.43 +/- 0.03 in the controls. A significant negative correlation was observed between CBF and the hematocrit (y = -1.79x + 120.7, r = -0.71, p less than 0.01). Calculating CBF from this equation in the dialyzed patients using a hematocrit of 0.43 yielded a mean CBF value of 43.7 ml 100 g-1 min-1, i.e., 20% below the expected. Two patients showed a focal CBF decrease. CT showed central or cortical atrophy in five patients, and two had small hypodense lesions. The neurological examination revealed slight to moderate dementia in seven cases. Although mean CBF was found to be increased by 21% as compared to the control group, an even higher CBF level would have been expected to outweigh the decreased oxygen carrying capacity of the blood. The findings suggest a lowered metabolic demand of the brain tissue, probably due to subtle brain damage. PMID- 1506443 TI - Distributions of heat shock protein-70 mRNAs and heat shock cognate protein-70 mRNAs after transient global ischemia in gerbil brain. AB - Distributions of heat shock protein (HSP)-70 mRNAs and heat shock cognate protein (HSC)-70 mRNAs after 10 min of transient global ischemia were investigated in gerbil forebrain by in situ hybridization using cloned cDNA probes selective for the mRNAs. Expression of HSP70 immunoreactivity was also examined in the same brains. In hippocampal CA1 neuronal cells, in which only a minimal induction of immunoreactive HSP70 protein was found, the strong hybridization for HSP70 mRNA disappeared at around 2 days before the death of CA1 cells became evident. Furthermore, in hippocampal CA3 cells, a striking induction of HSP70 mRNA was sustained even at 2 days along with a prominent accumulation of HSP70 immunoreactivity. In contrast to the case of HSP70 mRNA, HSC70 mRNA was present in most neuronal cells, especially dense in CA3 cells, of the sham brain. A co induction of HSP70 and HSC70 mRNAs was observed in several cell populations after the reperfusion with a peak at 8 h, although the magnitude of HSC70 mRNA induction was lower than that of HSP70 mRNA, particularly in CA1 cells. The expression of HSC70 mRNA in CA1 cells also disappeared at around 2 days. All the induced signals of HSP70 and HSC70 mRNAs in other cell populations were diminished and returned to the sham level, respectively, by 7 days. These results are the first to show the time courses of distribution of HSP70 and HSC70 mRNAs and the immunoreactive HSP70 protein in the same gerbil brain after ischemia.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1506444 TI - Uncoupled cerebral blood flow and metabolism after severe global ischemia in rats. AB - In a rat model of complete global brain ischemia (neck tourniquet) lasting either 3 min or 20 min, we monitored global CBF (sagittal sinus H2 clearance) and CMRO2 for 6 h to test the hypothesis that delayed postischemic hyperemia and uncoupling of CBF and CMRO2 occur depending on the severity of the insult. Early postischemic hyperemia occurred in both the 3-min and 20-min groups (p less than 0.05 vs. baseline values) and resolved by 15 min. Hypoperfusion occurred in the 3 min group between 15 and 60 min postischemia (approximately 23% reduction), and in the 20-min group from 15 to 120 min postischemia (approximately 50% reduction) (p less than 0.05), and then resolved. CMRO2 was not significantly different from baseline at any time after ischemia in the 3-min group. After 20 min of ischemia, however, CMRO2 was decreased (approximately 60%) throughout the postischemic period (p less than 0.05). At 5 min after ischemia, CBF/CMRO2 was increased in both groups but returned to baseline from 60 to 120 min postischemia. In the 3 min group, CBF/CMRO2 remained at baseline throughout the rest of the experiment. However, in the 20-min group, CBF/CMRO2 once again increased (approximately 100%), reaching a significant level at 180 min and remaining so for the rest of the 6-h period (p less than 0.05). These data demonstrate biphasic uncoupling of CBF and CMRO2 after severe (20 min) global ischemia in rats. This relatively early reemergence of CBF/CMRO2 uncoupling after 180 min of reperfusion is similar to that observed after prolonged cardiac arrest and resuscitation in humans. PMID- 1506445 TI - Influence of preischemic hyperglycemia on osmolality and early postischemic edema in the rat brain. AB - Preischemic hyperglycemia, which raises tissue lactate content during ischemia, is known to aggravate ischemic brain damage. To explore the possibility that the enhanced lactic acidosis gives rise to osmotic damage, we studied the influence of a varied preischemic plasma glucose concentration on the early postischemic edema. Brain edema was measured by the specific-gravity technique. Brain and plasma osmolality were measured with a vapor pressure osmometer. We examined different brain regions in hyperglycemic and moderately hypoglycemic rats subjected to 15 min of forebrain ischemia, followed by recirculation for 5, 15, and 30 min. The decrease in specific gravity was compared with the increase in osmolality, to study whether the edema formation in the different groups correlated to the increase in tissue osmolality. We found edema formation to be most pronounced in frontoparietal cortex. In this structure and in hippocampus, statistically significant decreases of specific gravity were seen at all recirculation times studied. In caudoputamen, significant edema was seen only in the groups with 5 and 15 min of recirculation. Contrary to expectations, no difference was found between hyperglycemic and hyperglycemic animals. Tissue osmolality increased during ischemia in both the low and high glucose groups, but to a higher level in the latter (hypoglycemia 311 +/- 1 mmol kg-1, hyperglycemia 328 +/- 10 mmol kg-1; mean +/- SD, p less than 0.05). In the hyperglycemic group, brain osmolality remained elevated for the first 15 min of recirculation.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1506446 TI - Methodological requirements for accurate measurements of brain and body temperature during global forebrain ischemia of rat. AB - The methodological requirements for accurate measurements of brain and body temperature during brain ischemia have been validated in Wistar rats submitted to 30 min of four-vessel occlusion. During ischemia, brains were exposed to three different temperature profiles: spontaneous cooling from 36 to 31 degrees C (n = 10), constant hypothermia at 30 degrees C (n = 19), and constant normothermia at 36 degrees C (n = 21). Direct and indirect brain temperature recordings were carried out by placing fine thermocouples (200 microns diameter) into the striate nucleus, the temporal muscle, and the epidural space. Body temperature was measured with a flexible thermocouple inserted at various depths into the rectum. Accurate measurements of body temperature required insertion of the rectal probe to a depth of at least 6 cm; lesser insertion resulted in an underestimation of up to 6 degrees C. Accurate estimates of brain temperature were obtained in all three experimental conditions by recording of the epidural temperature. The temperature in the temporal muscle, by contrast, differed from the brain temperature by up to 2 degrees C, depending upon the experimental condition and the duration of ischemia. We therefore suggest that indirect measurements of brain temperature during ischemia are carried out in the epidural space in order to avoid misinterpretations of temperature-sensitive pathological changes. PMID- 1506447 TI - Errors introduced by tissue heterogeneity in estimation of local cerebral glucose utilization with current kinetic models of the [18F]fluorodeoxyglucose method. AB - The effects of tissue heterogeneity on the estimation of regional cerebral glucose utilization (rCMRglc) in normal humans with [18F]2-fluoro-2-deoxy-D glucose ([18F]FDG) and positron emission tomography (PET) were compared with respect to the various kinetic models of the [18F]FDG method. The kinetic models were conventional homogeneous tissue models of the [18F]FDG method, with (4K Model) and without (3K Model) a rate constant to account for an apparent loss of [18F]2-fluoro-2-deoxy-D-glucose-6-phosphate ([18F]FDG-6-P), and a tissue heterogeneity model (TH Model). When either of the kinetic models designed for homogeneous tissues was applied to heterogeneous tissues, estimates of the rate constant for efflux of [18F]FDG from the tissue (k2*) and of the rate constant for phosphorylation of [18F]FDG (k3*) decreased as the duration of the experimental period was increased. When the 4K Model was used, estimates of the rate constant for the apparent dephosphorylation of [18F]FDG-6-P (k4*) were significantly greater than zero and fell with increasing duration of the experimental period. Although the TH Model included no term to describe an apparent dephosphorylation of [18F]FDG-6-P, the fit of the TH Model to the time course of total tissue radioactivity was at least as good as and often better than the fit of the 4K Model in the 120-min period following the pulse of [18F]FDG. Hence, the high estimates of k4* found in PET studies of less than or equal to 120 min can be explained as the consequence of measuring radioactivity in a heterogeneous tissue and applying a model designed for a homogeneous tissue; there remains no evidence of significant dephosphorylation of [18F]FDG-6-P in this time period. Furthermore, use of the 4K Model led to an overestimation of rCMRglc; whole-brain glucose utilization calculated with the 4K Model was greater than 20% higher than values usually obtained in normal humans by the model independent Kety-Schmidt technique. rCMRglc was accurately estimated by the TH Model and, in experimental periods sufficiently long to minimize the effects of tissue heterogeneity, also by the original 3K Model of the deoxyglucose method. PMID- 1506448 TI - Sciatic nerve stimulation does not increase endogenous adenosine production in sensory-motor cortex. AB - Adenosine participates in the coupling of cerebral blood flow to oxygen consumption in the brain during such stimuli as hypoxia, ischemia, and seizures. It has been suggested that it also participates in the regulation of cerebral blood flow during somatosensory stimulation, a condition during which cerebral blood flow and oxygen consumption appear to be uncoupled. Interstitial adenosine was estimated by the microdialysis technique and cerebral blood flow was measured by hydrogen clearance in the hindlimb sensory-motor cortex during sciatic nerve stimulation. Cerebral blood flow increased from 102 to 188 ml min-1 100 g-1 (p less than 0.001) in the cortex contralateral to the stimulated leg without an associated increase in interstitial adenosine (baseline 0.624 microM, stimulation 0.583 microM). Infusion of the adenosine antagonist 8-sulfophenyltheophylline failed to block an increase in cerebral blood flow during central sciatic nerve stimulation, but decreased basal cerebral blood flow (69 ml min-1 100 g-1). These results suggest that adenosine does not mediate changes in cerebral blood flow during somatosensory stimulation, but may participate in the regulation of cerebral blood flow in the basal state. PMID- 1506449 TI - Stimulation of Cl area neurons globally increases regional cerebral blood flow but not metabolism. AB - We examined the effects of electrical and chemical stimulation of the Cl area of the rostral ventrolateral medulla (RVL) on regional cerebral blood flow (rCBF) and regional cerebral glucose utilization (rCGU) in anesthetized (chloralose), paralyzed (curare) and ventilated rats. rCBF and rCGU were measured using 14C iodoantipyrine (IAP) and 14C-deoxyglucose (2-DG), respectively, as indicators, with bilateral regional dissection of 11 brain regions. Electrical stimulation of the RVL elicited increases in arterial pressure (AP), heart rate (HR) and plasma concentration of epinephrine (EPI) and norepinephrine (NE). In addition, stimulation of the RVL, but not the adjacent medial longitudinal fasciculus, with AP maintained, increased rCBF (p less than 0.05, n = 6), but not rCGU, bilaterally and symmetrically (134-169% of control) throughout the brain. Bilateral adrenalectomy abolished the increase in plasma EPI elicited by stimulation of the RVL but did not affect resting rCBF (n = 5) or the elevation in rCBF elicited by RVL stimulation (n = 5). Increases in rCBF elicited by RVL stimulation were also unaffected by acute transection of the superior cervical ganglion (p greater than 0.05). Kainic acid (KA) microinjected into the RVL unilaterally (n = 6) at a dose producing sustained elevation in AP (5 nmol in 100 nl), elicited changes in rCBF similar to those elicited by electrical stimulation. We conclude that neurons within the RVL, possibly those of the adrenergic Cl group, can initiate a global cerebrovasodilation, but not an increase in rCGU, largely through neural pathways intrinsic to the brain. The responses may represent activation of networks in RVL mediating circulatory adjustments to hypoxia. PMID- 1506451 TI - Effects of indomethacin on myogenic contractile activation and responses to changes in O2 and CO2 in isolated feline cerebral arteries. AB - We used an isolated, pressurized, and perfused feline middle cerebral artery preparation to measure how changes in intraluminal pressure and alterations in O2 and CO2 affect vessel diameter and myogenic contractile activation before and after treatment with indomethacin (IND). Vessel diameters were measured over the pressure range 60-140 mm Hg. The arteries were then exposed to low O2 (50 torr) and/or high CO2 (65 torr) and diameters remeasured over the same range. Under control conditions, the arteries exhibited myogenic contractile activation. Exposure to low O2, high CO2, or a mixture of low O2/high CO2, increased vessel diameter but did not change the vessels' myogenic contractile responsiveness to changes in pressure. Arteries exposed to IND decreased in diameter but retained myogenic contractile activity. In the presence of IND, vessels dilated to both low O2 and a mixture of low O2/high CO2, but did not dilate to high CO2 alone. Under all conditions, vessels retained myogenic contractile activity. Results obtained under control conditions and low O2 confirm those of others using similar systems. Myogenic contractile activity in the presence of high CO2 or a mixture of low O2/high CO2 has not been previously reported. The dilation to low O2 but not to high CO2 in the presence of IND suggests that this drug's effects in cerebral arteries are not limited solely to inhibition of prostaglandin synthesis. PMID- 1506450 TI - Regulation of cerebral glucose metabolism in normal and polycythemic newborn lambs. AB - In contrast to previous investigations, a recent study of polycythemic lambs suggested that cerebral glucose delivery (concentration x blood flow), not arterial glucose concentration, determined cerebral glucose uptake. In the present study, the independent effects of arterial glucose concentration and delivery on cerebral glucose uptake were examined in two groups of chronically catheterized newborn lambs (control and polycythemic). Arterial glucose concentration was varied by an infusion of insulin. CBF was reduced in one group of lambs (polycythemic) by increasing the hematocrit. At all arterial glucose concentrations, the cerebral glucose delivery of the polycythemic group was 59.6% of the control group. At arterial glucose concentrations of greater than 1.6 mmol/L, cerebral glucose uptake was constant and similar in both groups. At arterial glucose concentrations of less than or equal to 1.6 mmol/L, cerebral glucose uptake was unchanged in the control group, but was significantly decreased in the polycythemic group. In contrast, the cerebral glucose uptake was similar in both groups over a broad range of cerebral glucose delivery values. At cerebral glucose delivery values less than or equal to 83 mumols/min/100 g, there was a significant decrease in cerebral glucose uptake in both groups. During periods of low cerebral glucose delivery and uptake, cerebral oxygen uptake fell in the control group but remained unchanged in the polycythemic group. Maintenance of cerebral oxygen uptake in the polycythemic group was associated with an increased extraction and uptake of lactate and beta-hydroxybutyrate. We conclude that cerebral glucose delivery, not arterial glucose concentration alone, determines cerebral glucose uptake. PMID- 1506452 TI - Intracerebral microdialysis of extracellular amino acids in the human epileptic focus. AB - Extracellular levels of aspartate (ASP), glutamate (GLU), serine (SER), asparagine (ASN), glycine (GLY), threonine (THR), arginine (ARG), alanine (ALA), taurine (TAU), tyrosine (TYR), phenylalanine (PHE), isoleucine (ILEU), and leucine (LEU) were monitored by using intracerebral microdialysis in seven patients with medically intractable epilepsy, undergoing epilepsy surgery. In association with focal seizures, dramatic increases of the extracellular ASP, GLU, GLY, and SER concentrations were observed. The other amino acids analyzed, including TAU, showed small changes. The results support the hypothesis that ASP, GLU, GLY, and possibly SER, play an important role in the mechanism of seizure activity and seizure-related brain damage in the human epileptic focus. PMID- 1506453 TI - The effect of profound levels of hypothermia (below 14 degrees C) on canine cerebral metabolism. AB - The goal of this study was to determine the temperature coefficient (Q10) for canine CMRO2 at temperatures below 14 degrees C. Eight dogs were anesthetized with halothane for surgical preparation. The animals were placed on total cardiopulmonary bypass and CBF was measured by direct sagittal sinus outflow. Duplicate measurements were taken at 37, 13, and 7 degrees C. The EEG became isoelectric at a temperature of 12.0 +/- 0.8 degrees C. The Q10 between 13 and 7 degrees C was 2.19 +/- 0.59. With rewarming to 37 degrees C, cerebral metabolic variables returned to control levels. Brain biopsies taken at the end of the study yielded normal values for brain energy stores. We conclude that the Q10 for CMRO2 at temperatures between 7 and 37 degrees C can be profoundly affected by the state of cerebral function as reflected by the EEG. In the absence of EEG activity, an expected Q10 value of 2.2 reflects only the direct effect of temperature on the rates of biologic reactions. PMID- 1506454 TI - Plasma L-[18F]6-fluorodopa input function: a simplified method. AB - This article describes a simplified method for the determination of the L-[18F]6 fluorodopa (FDOPA) fraction time course that takes advantage of the strong correlation between the radioactivity ratio (metabolites/FDOPA) and time. Serial arterial blood samples are collected for assay of plasma total radioactivities following an intravenous injection of FDOPA into carbidopapretreated subjects. In addition, a single plasma sample, collected late in the study and analyzed for FDOPA fraction, is sufficient to determine accurately the time course of the FDOPA concentration in plasma. The validated straight-line method greatly simplifies blood analysis for routine positron emission tomography FDOPA studies. PMID- 1506456 TI - Production of polyclonal antibodies in ascitic fluid of mice: time and dose relationships. AB - Further studies of the humoral immune response have been undertaken using ovine immunoglobulin G as the immunogen and BALB/C mice as the recipients. Mice immunized by the intraperitoneal route weekly for five weeks with an emulsion of the immunogen in Freund's complete adjuvant and given an intraperitoneal injection of pristane on day 14 produce relatively large volumes of ascitic fluid. A simple fluoroimmunoassay is used to determine specific antibody titres. The mice do not lose condition, remain active and eat normally throughout, although all show extensive granuloma formation within the peritoneal cavity. Tapping is performed before ascitic fluid production is excessive and each study is complete within 49 days, with a maximum of 5 taps. Only a single immunization site is required, since no higher antibody titres are obtained using combined intraperitoneal plus intramuscular plus subcutaneous immunization routes. A dose response study has shown that relatively large amounts (100 micrograms) of ovine immunoglobulin G must be injected to evoke a maximum response. Studies are in progress of various adjuvants and potential modulators of the immune response and of ways in which the immunogenicity of macromolecules can be changed. This approach can also be used to obtain antibodies for diagnostic purposes more rapidly than in rabbits and sheep. PMID- 1506455 TI - Enzyme-linked immunosorbent assay for the phytotoxin cleistanthin A. AB - Enzyme-linked immunosorbent assay is reported for the estimation of cleistanthin A, a major constituent of the toxic plant Cleistanthus collinus. Rabbit antibodies were obtained by immunisation with cleistanthin A hemisuccinate-BSA conjugate and the ELISA developed thereupon could detect cleistanthin A at as low a concentration as 3 ng/ml. Cross-reactivity studies with structural analogs as well as with other phytotoxins and drugs of common occurrence established the suitability of the ELISA to specifically monitor the C. collinus marker molecules in emergency clinical and forensic cases. The simplicity and specificity make the ELISA superior to the other available techniques. PMID- 1506457 TI - Two-sites immunoradiometric assay using monoclonal antibodies for the determination of serum human sex hormone binding globulin. AB - An immunoradiometric assay (IRMA) for the determination of human Sex Hormone Binding Globulin (SHBG) in serum is described. This IRMA uses three mouse monoclonal antibodies. Two monoclonals anti-human SHBG are coated on tubes and used as capture antibodies. The third monoclonal labeled with 125I completes the system, allowing the formation of the "sandwich". The detection limit of the assay is 2.5 femtomol SHBG per tube (250 pg/tube). Using this test for the measurement of SHBG and radioimmunoassays for the determination of total Testosterone and Estradiol, we calculated the Free Androgen Index (FAI) and the Free Testosterone. The results obtained were compared with the values of Free Testosterone measured by equilibrium dialysis. There is a close correlation between both calculated parameters and the levels of Free Testosterone, validating this SHBG assay. PMID- 1506458 TI - Development of a high capacity radioimmunoassay procedure: ovine follicle stimulating hormone determination in blood plasma as a model. AB - A sensitive, specific and accurate homologous radioimmunoassay (RIA) for ovine follicle stimulating hormone (oFSH) has been developed, using a [125I]oFSH tracer and a polyclonal rabbit anti-OFSH-serum at a final dilution of 1:224,000. The separation of free and antibody-bound tracer is based on the double antibody solid phase system. The assay was found to be specific for oFSH; cross-reactivity with oLH, oPrl and oGH was lower than 0.2%. The detection limit was 7 pg per tube. Inter- and intra- assay coefficients of variation (CV) were 3.7-8.5% and 6.6%, respectively. The use of a few selfmade appliances in combination with a well-considered time-schedule enabled the processing of three thousand blood plasma samples in triplicate within two weeks. The particular advantage of the method described here is the fast, easy and safe separation of free and antibody bound tracer with minimal handling of radioactive tubes. PMID- 1506459 TI - Detection of human anti-annexin autoantibodies by enzyme immunoassays. AB - Annexins belong to a family of proteins characterized by calcium-dependent binding to the cytoskeleton and phospholipid surfaces. Basing on these properties annexins are discussed to be involved in the regulation of cytodynamic, anticoagulatory and antiinflammatory processes. Since autoantibodies against annexin I had been detected in patients suffering from inflammatory or autoimmune diseases, an impact on the pathophysiological outcome was assumed. Therefore we developed solid phase, enzyme-linked immunoassays for the quantitative determination of autoantibodies directed against six members of the annexin family. Some preliminary results obtained from sera of patients with malignant melanoma show a quite frequent presence of such autoantibodies. These data suggest that autoantibodies are generated against all annexins. Furthermore, in the individual patient autoantibodies of the IgG-type are monospecific, while about 1/4 of the IgM-type are directed against several annexins. These observations imply that for investigation of anti-annexin autoantibodies in inflammatory and autoimmune diseases as well as cancer all members of the annexin family have to be taken into consideration. PMID- 1506460 TI - Rapid antibody capture assay for detection of group-A streptococci using monoclonal antibody and colloidal gold-monospecific polyvalent antibody conjugate. AB - A rapid one step, sensitive and specific antibody capture assay for detection of group-A streptococci from the throat swabs of children is described. Monoclonal antibody either MA-106 or MA-107 specific for group-A streptococci polysaccharide (APS) was used as the capture antibody on nitrocellulose paper and rabbit monospecific polyvalent antibody conjugated with colloidal gold to detect the presence of antigen. The lower detection limit of this assay is 15.6ng APS/ml. The assay is specific for APS and failed to recognize polysaccharides obtained from group-B,-C,-G streptococci as well as Staphylococcus aureus. Antigen extracted from throat swabs of children who were positive for beta-hemolytic plaques (other than group-A streptococci) as seen on blood agar culture gave negative readings, thereby confirming the specificity of the assay for APS. PMID- 1506461 TI - Improving the psychological status of children with asthma: a randomized controlled trial. AB - Children with asthma are at special risk for problems in psychological functioning, as are children with other chronic illnesses. We conducted a controlled trial of a combined education and stress management program among children ages 6 to 14 years with asthma. Eighty-one children were randomly assigned to an intervention or a control group; 56 children completed data collection, 29 intervention and 27 control. Psychological status was assessed by the Child Behavior Checklist (CBCL) before and after the intervention, as were children's knowledge of asthma, stress (as measured by children's life events), and functional status (as indicated by such activities as school attendance, time playing with friends, and daily chore performance). Children in the intervention group had a significant improvement in the total Behavior Problems score (p less than .04) and Internalizing scale (p less than .01) on the CBCL and a significant increase in daily chores (p less than .04) compared with the control group. Before intervention, the two groups had statistically significant positive relationships between negative life events and behavior problems scores. After intervention, children in the control group still demonstrated a significant relationship between negative life events and total and Internalizing Behavior Problem scores, although participation in the intervention group negated that relationship. Children in the intervention group whose knowledge of asthma increased were more likely to report an increase in daily chores (p less than .02). We conclude that the intervention had a beneficial effect on psychological status and on children's daily activities. The effect may have occurred in part by decreasing the likelihood that perceived stress from negative life events led to poorer adjustment. PMID- 1506462 TI - Home care for medically fragile children: impact on family health and well-being. AB - The health status of 48 families providing home care for their medically fragile children was studied. Mothers, as the primary caregivers, experienced a greater decline in their physical health than did fathers or siblings. When the financial burden of providing care was greater and when the relationship with care providers was more strained, families had more physical illness symptoms. Who provided home care services for the medically fragile child influenced the psychosocial impact on the family. Care provided by home health aides was associated with greater negative impact, whereas care from professional nurses reduced the negative impact. The trend toward home care for medically fragile children has been accelerating; this study points to the importance of studying the impact on the family of this kind of care. Policy implications regarding the amount and quality of services and payment for them are discussed. PMID- 1506463 TI - Impaired emotional health in children with mild reading disability. AB - Children with reading disabilities are at risk for emotional difficulties. There is some evidence that reading-disabled children with high socioeconomic status may be at risk of having low self-esteem. We conducted a preliminary study of the impact of reading disability on children's self-esteem and emotional health in a select group of mildly impaired reading disabled children with well-educated parents who were well informed about reading disabilities. We interviewed 28 healthy, preadolescent boys and girls with mean reading delay of 9.0 months and 39 comparable nonreading disabled children who formed the control group. Children and parents completed the Harter's Self-Perception Profile. Parents completed the Achenbach Child Behavior Checklist and Rand Mental Health Survey. We found that these mildly impaired reading-disabled children were more anxious and less happy than were nondisabled students despite having well-informed, well-educated parents (mean level of education = 17.0 years). Reading-disabled children considered themselves to be less competent scholastically, and their parents rated them as less competent than nondisabled children on all measures of self esteem. These well-educated mothers tended to underrate their child's perceived scholastic competence. Controlling for behavior problems, Achenbach Child Behavior Checklist scores for social competence were lower for reading-disabled children. These findings suggest that the mildly impaired reading-disabled children with high socioeconomic status are at risk for low self-esteem and poor emotional health. PMID- 1506464 TI - Gender differences in infirmary use at a residential summer camp. AB - Studies of health behavior in adults show that women report more morbidity and greater health service utilization than do men, despite lower mortality rates. Explanations involve social and biological gender differences in adult life. Infirmary utilization at a residential summer camp where parental influence is minimized was studied to determine whether these gender differences occur in the pediatric age group. Three hundred ninety-eight campers, 8 to 18 years old were studied. Girls were observed to make greater use of the infirmary than boys (p less than .01) and were especially likely to present with minor trauma, both musculoskeletal (p less than .05) and skin (p less than .01). No correlation was found between age and frequency of visits. Obvious morbidity was similar for boys and girls, in that no gender difference was observed in those visiting for definite medical indications alone or in those admitted. However, a difference was evident in those visiting for minor and trivial problems, particularly in those making three or more visits for minor and trivial problems (p less than .01). Although obvious morbidity was no different in campers, girls used the infirmary more than boys in a manner similar to that reported for adult health behavior. This suggests that gender differences occur earlier than suspected and are not simply related to adult social roles. PMID- 1506465 TI - Personality development, problem solving, and behavior problems among preschool children with early histories of nonorganic failure-to-thrive: a controlled study. AB - Using a prospective study design, 48 preschool children with early histories of nonorganic failure-to-thrive (NOFT) and 47 physically healthy children of comparable age, sex, birth order, and family demographics were compared on measures of problem solving and personality development (ego control and ego resiliency). In responding to structured measures, NOFT children demonstrated deficits in behavioral organization, ego control, and ego resiliency compared with controls. Parents also identified higher levels of behavioral symptoms in children with early histories of NOFT compared with controls. However, home observational measures of ego control and ego resiliency did not differentiate the two groups. Deficiencies in problem solving and personality development and increased levels of behavioral symptoms in preschool children with early histories of NOFT may affect their future socioemotional development and learning. PMID- 1506466 TI - Psychometric differentiation of conduct disorder and attention deficit disorder with hyperactivity. AB - Using a retrospective chart review procedure, children diagnosed as having attention deficit disorder with hyperactivity (ADDH), conduct disorder (CD), and ADDH+CD, as defined by DSM-III, were compared on measures of cognitive and academic functioning as well as on a continuous performance test (CPT). The groups did not differ in age or IQ, but children in the ADDH and ADDH+CD groups missed significantly more target stimuli on the CPT and performed significantly poorer on measures of academic achievement than did the pure CD group. However, poor CPT performance was not accounted for by learning problems. These findings in clinically referred patient groups are consistent with dimensional and epidemiological studies that suggest that ADDH may be a cognitively based disorder, whereas CD children are characterized by behavioral symptoms with fewer cognitive and learning deficits. PMID- 1506467 TI - Decreased serum bicarbonate as a manifestation of undernutrition secondary to nonorganic failure-to-thrive. AB - Eight of 101 children (8%) seen serially in consultation in an outpatient failure to-thrive (FTT) clinic had isolated serum bicarbonate (TCO2) levels between 16 and 20 MEQ/dL (normal 22 to 30 MEQ/dL). None of these eight patients had signs or symptoms of renal disease, and all had nonorganic etiologic factors associated with their malnutrition. At the time of this review, follow-up TCO2 measurements were available for seven of the eight children who had attained normal weight (wt/age greater than fifth percentile on National Center for Health Statistics (NCHS) growth chart). All these children had normal TCO2 levels and no evidence of renal disease on follow-up more than 12 months later. Clinicians treating undernourished children who have low TCO2 measurements and have no signs or symptoms of renal disease and identified nonorganic factors, should consider a trial of therapies directed at nonorganic factors. Clinicians should be aware that a high percentage of undernourished children without other medical disease may have abnormal TCO2 measurements that correct after the institution of adequate caloric intake. PMID- 1506468 TI - A complex chromosome rearrangement in a boy with autism. AB - Autism is a rare behavioral phenotype defined by a qualitative impairment in reciprocal social interaction, impairment in communication and imaginative activity, and a markedly restricted repertoire of activities and interests. It is the most severe and prototypical form of the general category of Pervasive Developmental Disorders of Childhood. Using even strict diagnostic criteria, the currently described etiologies of autism are heterogeneous, with the majority of cases continuing to be idiopathic. At present, it is not clear whether autism is merely a behaviorally defined phenotype arising from diverse etiologies or a separate category of psychological dysfunction for which some unifying etiology exists. Complex chromosome rearrangements (CCR) are rare structural abnormalities involving at least three chromosomes and three or more break-points. We report a 6.5-year-old boy with classic infantile autism and a CCR involving chromosomes 1, 7, and 21. We discuss the possible relationship of his chromosome abnormality to the etiology of his autism. PMID- 1506469 TI - A combined behavioral/pharmacological treatment of sleep-wake schedule disorder in Angelman syndrome. AB - Angelman syndrome (AS) is a genetic disorder associated with a deletion on chromosome 15. Behavior problems among children with AS include sleep difficulties. Data are presented on the successful treatment of a sleep-wake schedule disorder (SWSD) in a 9-year-old boy with AS. The treatment program included behavioral and pharmacological components. During baseline, the child slept a mean of 1.9 hours per night and 1.3 hours during the day; night sleep was increased to a mean of 8.3 hours and day sleep was reduced to a mean of .08 hours after introduction of the full-treatment program. Medication was discontinued subsequently, and the child slept a mean of 7.8 hours during the night and .07 hours during the day. At 45-day follow-up, night sleep was maintained at 7.1 hours and day sleep remained stable at .29 hours. This is the first known report of an effective treatment of a SWSD in a child with AS. PMID- 1506470 TI - The National Cholesterol Education Program pediatric guidelines: behavioral considerations. PMID- 1506471 TI - Adolescent tobacco, alcohol, and drug abuse: prevention strategies, empirical findings, and assessment issues. PMID- 1506472 TI - Light and electron microscopic characterization of dopamine-immunoreactive axons in human cerebral cortex. AB - The distribution and synaptic connections of dopamine axons were studied by light and electron microscopy in human cerebral cortex. For this purpose, dopamine immunoreactivity was characterized in apparently normal anteriolateral temporal cortex, which was removed to gain access to the medial temporal lobe during tumor excision or treatment of epilepsy. Nissl sections showed this to be granular neocortex. Dopamine fibers were distributed throughout this cortex, although there were relatively more fibers in layers I-II and in layers V-VIa, compared to layers III-IV and VIb, resulting in a bilaminar pattern of labeling. In all layers, fibers were seen to form numerous varicosities, and to vary in size from thick to very fine. Fibers were relatively straight, sparsely branched and were oriented in various planes within the cortex. However, in layer I, they often ran parallel to the pial surface. In order to analyze the functional interactions of dopamine fibers, individual cortical layers were surveyed for dopamine synapses. These were usually symmetrical (Gray's type II), although 13% of them were asymmetrical. Approximately 60% of dopamine synapses were made with dendritic spines, and 40% with dendritic shafts, and this ratio was similar in all layers. On both spines and shafts, it was common to see dopamine synapses closely apposed to an unlabeled asymmetric input, suggesting a dopamine modulation of excitatory input. Some postsynaptic dendritic shafts had features of pyramidal cells, including formation of spines. Since pyramidal cells are the major type of cortical spiny neuron, they probably represent the main target of dopamine synapses in this cortex. There were also dopamine profiles apposed to membrane densities on unlabeled axon terminals, suggesting another type of synaptic interaction. These findings provide the first documentation of dopamine synapses in the human cortex, and show that they form classical synaptic junctions. The location of these synapses on spines and distal dendrites, and their proximity to asymmetric synapses, suggest a modulatory role on excitatory input to pyramidal cells. PMID- 1506473 TI - Changes in lamination and neuronal survival in the isthmo-optic nucleus following the intraocular injection of tetrodotoxin in chick embryos. AB - We have studied how the development of the isthmo-optic nucleus (ION) is affected by electrical activity in the ION's axonal target territory, the contralateral retina. Electrical activity was blocked or reduced in the retina for various periods by tetrodotoxin injected intraocularly in different doses. The effects on the morphology of the retina appear to have been minor. During the ION's period of naturally occurring neuronal death (embryonic days 12 to 17), the injections substantially reduced this neuronal death and disrupted the development of lamination in the contralateral ION; there was also a lesser reduction in neuronal death in the ipsilateral ION. The dose of tetrodotoxin required to affect lamination was lower than that affecting neuronal death. Thus, the effects on neuronal death and on lamination were independent, since either could occur without the other. These effects were mediated by retrograde signals (probably two or more) from the eye; they occurred too early for the alternative anterograde route via the optic tectum (which projects to the ION) to be responsible. After embryonic day 17, the ION's response to intraocular tetrodotoxin changes abruptly from increased survival to total and rapid degeneration. PMID- 1506474 TI - Maintenance of targeting errors by isthmo-optic axons following the intraocular injection of tetrodotoxin in chick embryos. AB - We have studied the role of electrical activity in the elimination of axonal targeting errors, which is a normal process in brain development. The experiments were focused on the isthmo-optic nucleus (ION), which, in adults, projects in topographical order on the contralateral retina. During embryogenesis, however, a few isthmo-optic neurons project to the ipsilateral retina, and many project to topographically inappropriate parts of the contralateral one; both kinds of targeting error are known to be eliminated by the deaths of the parent neurons. We injected tetrodotoxin (TTX) intraocularly at embryonic days 13 and 15 and, on the latter, applied a retrograde label to the retina of the same eye. Embryos were fixed at embryonic day 17. In some embryos, the label was a peripherally placed fleck of the carbocyanine dye "diI"; the resulting retrogradely labeled neurons in the contralateral ION were much more widely scattered in the TTX injected embryos than in controls (errors in topography). In other embryos, the label was a solution of rhodamine-B-isothiocyanate (RITC) injected into the vitreous body; this yielded several ipsilaterally labeled isthmo-optic neurons in the TTX-injected embryos, but virtually none in the controls. The numbers of both kinds of aberrantly projecting neuron approached those previously reported near the beginning of the ION's period of neuronal death. We conclude that electrical activity plays an important role in the elimination of axonal targeting errors in the chick embryo's isthmo-optic system. PMID- 1506475 TI - Area 3a in the cat. II. Projections to the motor cortex and their relations to other corticocortical connections. AB - It is well known that area 3a in the cat may monosynaptically influence the activity of neurons in the motor cortex. Much less information is available, however, on the anatomy of these connections. By using single or combined injections of different retrograde axonal tracers, we investigated the topography (horizontal and laminar) of area 3a neurons projecting to the motor cortex, and the anatomical relationships between these neurons and those projecting to other areas (2, 5, and SII) which, in turn, project to the motor cortex. Area 3a projects to all parts of area 4 gamma, to area 4 delta, and to the agranular area 6 in the lateral bank of the presylvian sulcus (area 6 alpha gamma), but not to other parts of areas 4 and 6. This projection exhibits a loose topographic organization along the mediolateral dimension of area 3a, and, in many cases, arises predominantly from the rostral half of this area. Although single small injections in the motor cortex produced two or more separate patches of retrograde labeling in 3a, after simultaneous injections of fluorochromes in two separate loci there often appeared in area 3a overlapping populations of neurons which were labeled retrogradely by each of the dyes, but with very few double labeled neurons. In horseradish peroxidase (HRP) cases, 72% of area 3a neurons projecting to area 4 gamma were distributed in supragranular layers (mainly layer III), although the proportion of labeling in infragranular layers was larger when using fluorescent dyes. Double-labeled cells predominated in infragranular layers. These results have a bearing upon the functional roles that have been attributed to area 3a, as a cortical locus involved in muscle sensation, and a cortical relay to the motor cortex of rapid feedback information from muscle activity during movement. PMID- 1506476 TI - Immunocytochemistry of dopamine in the brain of the locust Schistocerca gregaria. AB - Catecholamine-induced histofluorescence studies have suggested a rich innervation of the locust brain by dopamine-containing neurons. To provide a basis for future studies on dopamine action in this insect, the location and morphology of neurons reacting with antisera against dopamine were investigated in the supraoesophageal ganglion of the locust, Schistocerca gregaria. In each brain hemisphere, about 100 interneurons in the midbrain and approximately 3,000 cells in the optic lobe show dopamine-like immunoreactivity. All major areas of the brain except the calyces of the mushroom body, the antennal lobe, large parts of the lobula, and some areas in the inferior lateral protocerebrum contain immunoreactive neuronal processes. The arborization patterns of most dopamine-immunoreactive cell types could be identified through detailed reconstructions. The central body exhibits the most intense immunostaining. It is innervated by at least 40 pairs of dopamine-immunoreactive neurons belonging to three different cell types. Additional arborizations of these neurons are in the superior protocerebrum and in the lateral accessory lobes. A group of 4 immunoreactive neurons with ramifications in the antennal mechanosensory and motor center gives rise to a dense meshwork of varicose fibers in the pedunculus and parts of the alpha- and beta-lobes of the mushroom body. Other cell types innervate the ventrolateral protocerebrum, the inferior protocerebrum and the posterior optic tubercles. Three descending neurons originating in the tritocerebrum exhibit dopamine-like immunoreactivity. In the optic lobe, about 3,000 columnar intrinsic neurons of the medulla and a group of centrifugal tangential cells with arborizations in the medulla and lamina are dopamine-immunoreactive.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1506477 TI - Diencephalic projections from the superficial and deep laminae of the medullary dorsal horn in the rat. AB - An important function of the medullary dorsal horn (MDH) is the relay of nociceptive information from the face and mouth to higher centers of the central nervous system. We studied the central projection pattern of axons arising from the MDH by examining the axonal transport of Phaseolus vulgaris-leucoagglutinin (PHA-L). Labeled axon and axon terminal distributions arising from the MDH were analyzed at the light microscopic level. After large injections of PHA-L into both superficial and deep laminae of the MDH in the rat, labeled axons were observed in the nucleus submedius of the thalamus (SUB), ventroposterior thalamic nucleus medialis (VPM), ventroposterior thalamic nucleus parvicellularis (VPPC), posterior thalamic nuclei (PO), zona incerta (ZI), lateral hypothalamic nucleus (LH), and posterior hypothalamic nucleus (PH). Restriction of PHA-L into only the superficial laminae resulted in heavy axon and varicosity labeling in the SUB, VPM, PO, and VPPC and light labeling in LH. In contrast, after injections into deep laminae, labeled axons were mainly distributed in ZI and PH; some were also in VPM and LH, and fewer still in PO and SUB. Varicosities in VPM, SUB, and PO were significantly larger than those in VPPC, ZI, LH, and PH. Varicosity density was highest in SUB and lowest in the VPPC. We concluded that there are two distinct nociceptive pathways, one originating from the superficial MDH and terminating primarily in the dorsal diencephalon and the second originating from deep laminae of the MDH and terminating primarily in the ventral diencephalon. We propose that in the rat, input from the deeper laminae is primarily involved in the motivational-affective component of pain, whereas input from the superficial MDH is related to both the sensory-discriminative and motivational-affective component of pain. PMID- 1506478 TI - Restoration of ascending noradrenergic projections by residual locus coeruleus neurons: compensatory response to neurotoxin-induced cell death in the adult rat brain. AB - There is clinical and experimental evidence that monoamine neurons respond to lesions with a wide range of compensatory adaptations aimed at preserving their functional integrity. Neurotoxin-induced lesions are followed by increased synthesis and release of transmitter from residual monoamine fibers and by axonal sprouting. However, the fate of lesioned neurons after long survival periods remains largely unknown. Whether regenerative sprouting may contribute significantly to recovery of function following lesions which induce cell loss has been questioned. We have previously analyzed the response of locus coeruleus (LC) neurons to systemic administration of the noradrenergic (NE) neurotoxin N-(2 chloroethyl)-N-ethyl-2-bromobenzylamine (DSP-4) to adult rats. This drug causes ablation of nearly all LC axon terminals within 2 weeks after administration, followed by a profound loss of LC cell bodies 6 months later. The present study was conducted to determine the fate of surviving LC neurons and to characterize their potential for regenerative sprouting during a 16 month period after DSP-4 treatment. The time-course and extent of LC neuron degeneration were analyzed quantitatively in Nissl-stained sections, and the regenerative response of residual neurons was characterized by dopamine-beta-hydroxylase immunohistochemistry. The results document that LC neurons degenerate gradually after DSP-4 treatment, cell loss reaching on average 57% after 1 year. LC neurons which survive the lesion exhibit a vigorous regenerative response, even in those animals in which cell loss exceeds 60-70%. This regenerative process leads progressively to restoration of the NE innervation pattern in the forebrain, with some regions becoming markedly hyperinnervated. In stark contrast to the forebrain, very little reinnervation takes place in the brainstem, cerebellum and spinal cord. These findings suggest that regenerative sprouting of residual neurons is an important compensatory mechanism by which the LC may regain much of its functional integrity in the presence of extensive cell loss. Furthermore, regeneration of LC axons after DSP-4 treatment is region-specific, suggesting that the pattern of reinnervation is controlled by target areas. Elucidation of the factors underlying recovery of LC neurons after DSP-4 treatment may provide insights into the compensatory mechanisms of central neurons after injury and in disease states. PMID- 1506479 TI - Sex differences in the gross size of the rat neocortex. AB - The pervasiveness of sex differences in the size of the rat cerebral cortex was investigated in ten littermate pairs of socially housed Long-Evans hooded rats at 90 days of age. Overall, the cortex was longer and wider in male than in female rats. Sex differences were detected in most cortical regions with this sample size; the exception was the temporal cortex. While some asymmetries were found, they did not vary with the sex of the animal nor were they consistently in one direction. The contribution of the cortical layers to sex differences in cortical thickness was examined in four locations: the primary motor cortex, the forelimb area of the sensorimotor cortex and the monocular and the binocular areas of the visual cortex. The layers that showed sex differences varied among the areas but were confined to layers II-III, V and VI. Sex differences in cortical size were widespread in the adult rat but showed some regional and laminar specificity. PMID- 1506480 TI - Sex differences in neuron number in the binocular area of the rat visual cortex. AB - We have previously shown that the thickness of the binocular area of the primary visual cortex is sexually dimorphic in rats. In the present study, sex differences in the number of neurons in this cortical area were examined in nine littermate pairs of 90-day-old Long-Evans hooded rats. Cytoarchitectonic characteristics were used to define the binocular visual cortex, and its volume was estimated through three-dimensional reconstruction of serial coronal sections for each hemisphere. Neuronal and glial density as well as neuronal soma size were estimated from semithin sections through a stereological technique, the disector, in the same animals that were used to estimate volume. The volume of the binocular area was 19% greater in males than in females. While there were no sex differences in soma size or in neuronal density, the differences in the volume of the binocular area resulted in significant sex differences (male greater than female) in the number of neurons overall and in every layer, except layer IV. Glial density was not different between the sexes, but the total number of glial cells was higher in males than in females. These results demonstrate that the binocular visual cortex of the rat is sexually dimorphic in its volume and much of the difference is due to sex differences in the number of neurons and glial cells. PMID- 1506481 TI - Localization of kynurenine aminotransferase immunoreactivity in the rat hippocampus. AB - The localization and distribution of kynurenine aminotransferase (KAT), the biosynthetic enzyme of the excitatory amino acid receptor antagonist, kynurenic acid, was studied in the rat hippocampal formation with immunohistochemical methods. The enzyme was found mainly in glial cells that could be distinguished as 3 types on the basis of their shapes and locations. Typically, these cells shared the morphological features of astrocytes and exhibited glial fibrillary acidic protein immunoreactivity as demonstrated by a double-labeling technique. The distribution of KAT-containing glial cells was heterogeneous throughout the hippocampal formation. In the hippocampus, the stratum lacunosum-moleculare of Ammon's horn and the hilus contained a higher density of KAT-positive glial cells than other regions, whereas the lowest density of KAT glial cells was observed in the granule cell layer of the dentate gyrus and in the stratum radiatum of CA subfields. In the subicular complex, the density of KAT-containing glial cells was generally higher in the superficial than in the deep layer. Hippocampal neurons exhibiting KAT immunoreactivity, distinguished as nonpyramidal cells, were very few in number and mainly distributed in strata oriens and pyramidale of Ammon's horn. Substantially more KAT-positive neurons were observed in layers II and III of the subicular complex. The organization of cellular elements containing KAT may be of relevance for the function and possible dysfunction of kynurenic acid in the rat hippocampal formation. PMID- 1506482 TI - Retrograde tracing of projections between the nucleus submedius, the ventrolateral orbital cortex, and the midbrain in the rat. AB - The fluorescent tracers fluoro-gold and 1,1'-dioctadecyl-3,3,3,3-tetramethyl indocarbocyanine perchlorate were used as retrograde markers to examine reciprocal connections between the rat nucleus submedius and the ventrolateral orbital cortex. In addition, midbrain projections to each of these regions were examined. In the prefrontal cortex, we found that input from the nucleus submedius terminates rostrally within the lateral and ventral areas of the ventrolateral orbital cortex. Conversely, the cortical input to the nucleus submedius originates from the medial and dorsal parts of the ventrolateral orbital cortex. Our data also demonstrated that neurons from the ventrolateral periaqueductal gray and the raphe nuclei project to the midline nuclei of the thalamus, including a small projection to the nucleus submedius. We further determined that regions within the ventrolateral periaqueductal gray and raphe nuclei project to the ventrolateral orbital cortex, and that these regions overlap with those that project to the nucleus submedius. These findings suggest that the nucleus submedius might be part of a neural circuit involved in the activation of endogenous analgesia. PMID- 1506483 TI - GABAergic neurons in the mammalian inferior olive and ventral medulla detected by glutamate decarboxylase immunocytochemistry. AB - Neurons containing glutamic acid decarboxylase (GAD) (presumed GABAergic neurons) were mapped by immunocytochemistry in the ventral medulla of rat, rabbit, cat, rhesus monkey, and human, with emphasis on the inferior olive. In all species, three categories of GABAergic neurons were identified: periolivary neurons in the gray matter and the white matter surrounding the inferior olive, internuclear neurons located in the white matter between the subnuclei of the inferior olive, and intranuclear neurons located within the olivary gray matter. The intranuclear GABAergic neurons of the inferior olive had a characteristic morphology which differed from non-GABAergic olivary neurons; they were usually smaller, and, wherever their processes were stained, they had radiating, sparsely branching dendrites. They were also usually distinguished from the other GABAergic neurons by their smaller size. The intraolivary GABAergic neurons constituted only a minor proportion of the total olivary neuronal population, but they were concentrated in regions of the olive that varied by species. In the rat, they were situated in the rostral tip of the medial accessory olive and in the caudal subdivision of the dorsal accessory olive, while in the rabbit, they were located in the caudal two-thirds of the medial accessory olive, in the dorsal cap, and in the ventral lateral outgrowth. Such neurons were extremely rare in the cat; only a few were found in the rostral parts of the principal olive, the medial accessory olive, and the dorsal accessory olive. In the rhesus monkey, the principal olive and the lateral region of the rostral medial accessory olive contained most of the intranuclear GABAergic neurons, but some were also present in the dorsal accessory olive. In the human, such neurons occurred in the principal olive, the dorsal accessory olive and the rostral medial accessory olive, but as in the rhesus monkey, most were observed in the principal olive. PMID- 1506484 TI - Common synaptic drive to segmentally homologous interneurons in the locust. AB - The aim of the present study was to examine the pattern of synaptic interactions among a set of identified homologous interneurons in the segmental nervous system of the locust. This paper presents two main findings: first, serially homologous interneurons that are the progeny of neuroblast 7-4 in the mesothoracic, metathoracic, and first abdominal neuromeres of the locust central nervous system all receive synaptic drive from one and the same presynaptic interneuron. This interneuron has its entire arborization located in these three neuromeres of the central nervous system. It synapses with cells that are siblings, bilateral homologs, and serial homologs, and is itself connected monosynaptically with auditory afferents. The neuronal network that results comprises postsynaptic cells with the same developmental lineage. The second finding is that there is an additional set of synaptic connections among the homologous neurons themselves. All these connections are excitatory, and the pattern of information flow within the network is highly directional. This may relate to the morphologies of the neurons involved and will influence the contribution of homologs from different segments to behavior. PMID- 1506485 TI - Development of high-affinity choline transport sites in rat forebrain: a quantitative autoradiography study with [3H]hemicholinium-3. AB - The development of cholinergic terminals in rat brain has been quantitatively analyzed by [3H]hemicholinium-3 autoradiography. [3H]Hemicholinium-3 binds to high affinity choline transport sites, a specific marker for cholinergic neurons. In neonatal animals, kinetic and pharmacologic binding characteristics and regional distribution of [3H]hemicholinium-3 sites are consistent with specific cholinergic localization, as in the adult. The distribution of cholinergic terminals is described in the adult rat brain and during development, including heterogeneity of binding within several regions such as the striatum, nucleus accumbens, olfactory tubercle, cortex, and hippocampus. Early development and maturation vary greatly between brain regions. At embryonic day E18 and day 0, specific binding density is high only in the medial habenula. Development occurs primarily during the postnatal period in most brain regions examined. Many brain regions exhibit a lull in development between days 5 and 10, although the rate of development is highly region specific. Specific binding increases 2-12-fold between day 5 and adult animals, with adult density being achieved anywhere from day 15 to after day 21. The ontogeny of [3H]hemicholinium-3 binding sites generally occurs in a rostral to caudal direction. In the striatal body the characteristic lateral to medial gradient of binding site density is apparent by day 5, and development is more rapid in the lateral striatum. Patches of dense [3H]hemicholinium-3 binding coincident with acetylcholinesterase are observed on day 5 in the caudal striatum. The various patterns of cholinergic terminal development suggest that factors regulating cholinergic development are regional and complex. PMID- 1506486 TI - Morphology of the dorsal cochlear nucleus in C57BL/6J and CBA/J mice across the life span. AB - The morphology of the dorsal cochlear nucleus (DCN) was evaluated across the life span in inbred C57BL/6J (C57) and CBA/J (CBA) mice using 5 age groups (young adult to very old). C57 mice exhibit progressive cochlear sensorineural pathology and hearing loss during middle age; CBA mice have only modest sensorineural pathology late in life. DCN layers I, II, and III were evaluated histologically with serial sections stained for Nissl and fibers. DCN volume decreased with age in C57 mice, but the change began earliest and was most pronounced in layer III. In CBA mice, volume increased during the first year of life and decreased only in the oldest mice. All major DCN cell types were found in both strains at all ages. There was an age-related decrease in the mean size of neurons in C57 mice that was first observed in layer III. In CBA mice, only a nonsignificant trend toward smaller neurons was observed in the oldest mice. An age-related decline in the number of neurons in layer III (but not in layers I and II) occurred in C57 mice. Aged CBA mice exhibited no significant loss of DCN neurons. Thus, age-related changes in the DCN were much more pronounced in C57 mice than in CBA mice, and the changes in C57 mice were most pronounced in layer III. Because layer III receives most of the DCN's primary auditory input, it would be directly affected by age-related hearing loss and degeneration of spiral ganglion cells in C57 mice. This suggests that the age-related changes observed in DCN layer III of C57 mice are affected by progressive peripheral degenerative changes; when peripheral loss is minimal (CBA mice), less substantial age-related changes are observed. PMID- 1506487 TI - Relationships between lipid availability and protein utilization during prolonged fasting. AB - Mammals and birds adapt to prolonged fasting by mobilizing fat stores and minimizing protein loss. This strategy ends with an increase in protein utilization associated with behavioural changes promoting food foraging. Using the Zucker rat as a model, we have investigated the effect of severe obesity on this pattern of protein loss during long-term fasting. Two interactions between the initial adiposity and protein utilization were found. First, protein conservation was more effective in obese than in lean rats: fatty rats had a three times lower daily nitrogen excretion and proportion of energy expenditure deriving from proteins, and a lower daily protein loss in various muscles. This phase of protein sparing is moreover nine times longer in the fatty rats. Second, obese animals did not show the late increase in nitrogen excretion that occurred in their lean littermates. Total body protein loss during starvation was larger in fatty rats (57% versus 29%) and, accordingly, total protein loss was greater in their muscles. At the end of the experiment, lean and obese rats had lost 98% and 82%, respectively, of their initial lipid reserves, and fatty rats still had an obese body composition. These results support the hypothesis that in severely obese humans and animals a lethal cumulative protein loss is reached long before the exhaustion of fat stores, while the phase of protein conservation is still continuing. In contrast, in lean rats, survival of fasting seems to depend on the availability of lipid fuels.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1506488 TI - Adaptations of the reed frog Hyperolius viridiflavus (Amphibia: Anura: Hyperoliidae) to its arid environment. VI. The iridophores in the skin as radiation reflectors. AB - Hyperolius viridiflavus possesses one complete layer of iridophores in the stratum spongiosum of its skin at about 8 days after metamorphosis. The high reflectance of this thin layer is almost certainly the result of multilayer interference reflection. In order to reflect a mean of about 35% of the incident radiation across a spectrum of 300-2900 nm only 30 layers of well-arranged crystals are required, resulting in a layer 10.5 microns thick. These theoretical values are in good agreement with the actual mean diameter of single iridophores (15.0 +/- 3.0 microns), the number of stacked platelets (40-100) and the measured reflectance of one complete layer of these cells (32.2 +/- 2.3%). Iridescence colours typical of multilayer interference reflectors were seen after severe dehydration. The skin colour turned from white (0-10% weight loss) through a copper-like iridescence (10-25% weight loss) to green iridescence (25-42%). In dry season state, H. viridiflavus needs a much higher reflectance to cope with the problems of high solar radiation load during long periods with severe dehydration stress. Dry-adapted skin contains about 4-6 layers of iridophores. The measured reflectance (up to 60% across the solar spectrum) of this thick layer (over 60 microns) is not in keeping with the results obtained by applying the multilayer interference theory. Light, scattered independently of wavelength from disordered crystals, superimposes on the multilayer-induced spectral reflectance. The initial parallel shift of the multilayer curves with increasing thickness and the almost constant ("white") reflectance of layers exceeding 60 microns clearly point to a changing physical basis with increasing layer thickness. PMID- 1506489 TI - Effect of ambient temperature and E. coli endotoxin upon the plasma iron level in wild house mice in winter season. AB - The effects of ambient temperatures of 10 degrees C and 30 degrees C and of E. coli endotoxin on brain temperature and plasma iron level were investigated in unrestrained wild house mice, Mus musculus. In control animals (i.p. saline injected) exposed to cold environment the brain temperature decreased and plasma iron levels were lower than those observed under thermoneutral conditions (30 degrees C). Animals injected i.p. with endotoxin (0.5 micrograms.kg-1) and placed at 30 degrees C showed a drop in plasma iron level during the fever episode. The results provide strong evidence for a relationship between brain temperature and plasma iron level in control mice under thermoneutral conditions, and show that during cold exposure or after injection of endotoxin, there is no linear correlation between brain temperature and plasma iron. Moreover, it was found that cold stress influences plasma iron level and that this influence is not mediated by changes in brain temperature. PMID- 1506490 TI - K+ current stimulation by Cl- in the midgut epithelium of tobacco hornworm (Manduca sexta). II. Analysis of Ba(2+)-induced K+ channel conduction noise. AB - Chloride-stimulated K+ secretion by Manduca sexta midgut (5th-instar larvae) was measured as K(+)-carried short-circuit current of the tissue mounted in an Ussing chamber. "Microscopic" parameters, such as single-channel current and channel density for the rate-determining passive transport step across the basolateral goblet cell membrane (i.e. K+ channels), were estimated by means of current fluctuation analysis of the K+ channel blockade by haemolymph-side Ba2+ ions. Ba2+ was equally effective with Cl- or gluconate (Glu-) as the principal ambient anion. The Ba(2+)-induced K+ channel conduction noise is reflected by a Lorentzian, or relaxation, noise component in the power spectrum of the K+ current fluctuations. A reduced Lorentzian plateau value, but an unchanged corner frequency, were observed when Cl- was replaced by Glu-. The results from the analysis of a "two-state" model of K+ channel block by Ba2+, with respect to the anion-replacement effects, suggest that the observed changes in K+ current and Lorentzian plateau value mirror a complex change of the underlying parameters: Cl omission reduces single channel current but increases channel density so that the product of single channel current and channel density is smaller in Glu- than in Cl-. It seems likely that basolateral K+ channels (1) are subject to anionic gating ligands, and (2) depend on anions with respect to the rate of K+ transfer through an open K+ channel. PMID- 1506491 TI - The role of elongation factors in protein synthesis rate variation in white teleost muscle. AB - Protein synthesis-stimulating activity was assayed in the cytosolic fraction of white muscle from teleost fish (rainbow trout, carp) and of rat liver. In vitro protein synthesis-stimulating activity in the cytosolic fraction is reduced by food deprivation. The addition of elongation factors EF1, EF2, or EF1 + EF2 compensates for the starvation-induced loss of protein synthesis-stimulating activity in trout muscle cytosol. The action of EF2 is stronger than that of EF1 in this respect. However, EF1 enhances in vitro protein synthesis-stimulating activity in rat liver cytosol more than EF2. The EF2 concentration in the cytosolic fraction of white muscle from starved trout is significantly lower than in fed specimens. PMID- 1506492 TI - Dietary protein levels affect growth and protein metabolism in trunk muscle of cod, Gadus morhua. AB - Cod (Gadus morhua) of 50 g body weight were kept at 14 degrees C. The fish were fed ad libitum during 80 days a diet containing protein levels which in terms of total energy corresponded to 25%, 45% or 65%. Growth increased in accordance with protein-energy levels. The protein content per gram of wet weight of white trunk muscle was unchanged, as was the myofibrillar protein myosin heavy chain determined by the antigen-antibody reaction of the enzyme-linked immunosorbent assay. The amount of messenger ribonucleic acid (mRNA) coding for myosin heavy chain was lower at 25% than at 45% or 65% protein-energy intake, the differences being significant per gram of wet weight of muscle. Acid proteinase activity was highest at the lowest protein-energy intake. Glycogen content in muscle increased with the protein-energy levels. It is concluded that the metabolic response of white trunk muscle to graded protein-energy intake included a change in the capacity to synthesize myosin heavy chain as judged by its mRNA content. The protein content per gram of wet weight was unaffected by dietary protein-energy levels of 25%, 45% and 65%, but protein accretion and thus growth of the animals increased with the protein intake. Dietary protein-energy restriction caused a rise in acid proteinase activity and a decrease in content of mRNA for myosin heavy chain, resulting in a diminished growth rate at an unchanged protein content per gram of wet weight of muscle. PMID- 1506493 TI - Renal, respiratory and ionic regulation in Atlantic salmon (Salmo salar L.) kelts following transfer from fresh water to seawater. AB - Atlantic salmon may return to the sea after spawning in fresh water. These fish, known as kelts, reportedly show a limited ability to hypoosmoregulate. However, this study shows that fresh-water-adapted kelts exposed to seawater demonstrate rapid adaptation (within 48 h) in osmoregulatory parameters to values characteristics of seawater-adapted salmonids. The urine flow rate falls from 1.2 to 0.2 ml.kg-1.h-1 within 24 h. Over the same period, urine osmolality increases from 48 mosmol.kg-1 to become isosmotic with the plasma, and Mg2+ secretion by the kidney tubules elevates the urine concentration from 0.5 to 100 mmol.l-1. As is characteristic for marine teleosts, kelts drink seawater and process the ingested water in the gut to replace body water lost by osmosis to the hyperosmotic medium. Seawater exposure causes a marked hypoxia, arterial oxygen tension falling by 43% within minutes and persisting for at least 4 days at this low level. This is associated with large changes in blood pH and acid-base balance. The physiological mechanisms involved in adaptation to a hyperosmotic external medium are discussed, and the osmoregulatory capacity of kelts is compared with that of salmon at other stages of the life cycle. PMID- 1506494 TI - Flight muscle catabolism during overnight fasting in a passerine bird, Eremophila alpestris. AB - Brood-rearing passerine birds often have sparse lipid reserves coupled with potentially high energy demands. This may necessitate increased fasting protein catabolism; however, the largest source of protein, flight muscle, must be maintained. This problem was examined in the horned lark (Eremophila alpestris), a 28-g passerine. Overnight fasting caused significant depletion of protein in flight muscle and liver, but not in other muscle groups. Proteolytic enzyme activity of the flight muscle doubled during fasting. Biochemical and ultrastructural studies revealed that protein was depleted disproportionately from the sarcoplasm of flight muscle cells. Fasting caused a reduction in the protein-specific glycolytic capacity of flight muscle tissue. Oxidative capacity of the flight muscle, as measured by both in vivo and in vitro assays, was not significantly affected. The disproportionate catabolism of flight muscle sarcoplasmic protein may be due to a greater susceptibility to proteolysis, and not necessarily because it represents a source of redundant storage protein. PMID- 1506495 TI - Special issue. Behavioral Medicine: an update for the 1990s. PMID- 1506496 TI - Introduction to the special issue on behavioral medicine: an update for the 1990s. PMID- 1506497 TI - Role of behavior theory in behavioral medicine. AB - Behavioral medicine is a multidisciplinary field that combines research methods and findings from behavioral and biomedical sciences. Many investigators in the field have tended to emphasize the contribution of the biomedical more than the behavioral sciences. This is evident in the emphasis on biological rather than behavioral outcomes and on the reductionist approach within the field to reduce mechanisms responsible for behavioral effects and disease to biological influences. There has been a similar shift in psychology toward mechanistic, bottom-up approaches to understanding mechanisms responsible for integrated and dynamic behavior. These shifts in emphasis have stimulated investigators to examine the use of biomedical methods and findings as causes and explanations for behavior, rather than to utilize newer findings in behavioral sciences. New advances in basic research on learning are used to illustrate that findings from behavioral science have implications for the field of contemporary behavioral medicine. Finally, the importance of developing new technologies for measuring behavior is presented. PMID- 1506498 TI - Some structural changes that might facilitate the development of behavioral medicine. AB - Three types of organizational change are considered that may facilitate the development of behavioral medicine teaching, practice, and research over the next decade. The first and most critical of these changes is a consideration of the role of a Department of Behavioral Medicine within the medical school. The second is support for the development of research collaborations across centers, with the advantage of bringing a broader array of expertise and facilities to the solution of health problems. Finally, some changes in the role and organization of scientific societies that support behavioral medicine are considered. It is argued that, without such changes, behavioral medicine will become overly narrow in its focus and will not have the impact on the medical arena that it might otherwise have. PMID- 1506499 TI - Etiology and treatment of obesity: understanding a serious, prevalent, and refractory disorder. AB - Obesity remains a leading public health problem because of its complications, prevalence, and resistance to change, despite record rates of dieting. Risk factors exist at both population and individual levels, thus obesity has diverse etiologies and consequences. Dieting is often grounded in the notion that the body can be molded at will and that the rewards justify the effort, creating a drive for unrealistic goals. This article argues for establishing a "reasonable weight," which may differ from health and aesthetic ideals. Intervention is less a matter of finding a "best" treatment but of finding the approach with "best fit" for the individual. Advances in treatment are most likely when research is driven by theory on the etiology of weight gain, the relapse process, and methods for permanent behavior change. This article integrates information on etiology, social beliefs about body weight, theory, and treatment into a comprehensive and compassionate model for intervention. PMID- 1506500 TI - Smoking cessation: what have we learned over the past decade? AB - This article discusses developments in understanding smoking and smoking cessation, methodological issues, and intervention approaches over the past 10 years. Although effective multisession clinic interventions have been developed, such programs reach relatively few smokers. This has led to self-help, work site, health care setting, and community interventions aimed at delivering less intensive programs to larger populations. Conceptual and empirical developments and trends within these above delivery contexts are reviewed, and avenues of research are identified. Nicotine replacement strategies have benefited from technological advances (e.g., transdermal patches) and present continuing challenges with respect to integration with behavioral strategies and incorporation into primary care medical settings. Research over the next decade should focus on the development of cost-effective interventions that can reach representative and high-risk smokers. PMID- 1506501 TI - Behavioral and cognitive-behavioral approaches to chronic pain: recent advances and future directions. AB - Behavioral and cognitive-behavioral approaches to chronic pain are receiving increasing attention from researchers and clinicians. This article reviews and highlights recent research advances and future research directions. Assessment research reviewed includes studies examining the social context of pain, the relationship of chronic pain to depression, cognitive variables affecting pain, and comprehensive assessment measures. Treatment outcome studies reviewed are those evaluating the effects of behavioral and cognitive-behavioral treatments for chronic pain. These studies focus on comparisons of behavioral treatment with control conditions, comparisons of two behavioral treatments, and prevention of chronic pain. Future directions for assessment and treatment research are outlined. PMID- 1506502 TI - Psychological treatment of benign headache disorders. AB - This article presents a selective summarization and critique of research on the psychological treatment of headache, with the primary focus on research appearing since 1980. Suggestions for future research directions and methodological improvements are included. PMID- 1506504 TI - Psychoneuroimmunology: can psychological interventions modulate immunity? AB - There is ample evidence from human and animal studies demonstrating the downward modulation of immune function concomitant with a variety of stressors. As a consequence, the possible enhancement of immune function by behavioral strategies has generated considerable interest. Researchers have used a number of diverse strategies to modulate immune function, including relaxation, hypnosis, exercise, classical conditioning, self-disclosure, exposure to a phobic stressor to enhance perceived coping self-efficacy, and cognitive-behavioral interventions, and these interventions have generally produced positive changes. Although it is not yet clear to what extent these positive immunological changes translate into any concrete improvements in relevant aspects of health, that is, alterations in the incidence, severity, or duration of infectious or malignant disease, the preliminary evidence is promising. PMID- 1506503 TI - Psychological interventions for cancer patients to enhance the quality of life. AB - Although the thrust of the nation's cancer objectives for the year 2000 is prevention and screening, each year approximately 1 million Americans are diagnosed and must cope with the disease and treatments. They do so with the aid of family, friends, and the health care system, but accumulating data suggest that psychological interventions may be important for reducing emotional distress, enhancing coping, and improving "adjustment." Experimental and quasi experimental studies of psychological interventions are reviewed, and discussion of treatment components and mechanism is offered. A final section discusses future research directions and challenges to scientific advance. PMID- 1506505 TI - Psychological interventions with AIDS and HIV: prevention and treatment. AB - In the decade since acquired immune deficiency syndrome (AIDS) was first diagnosed, behavioral research has focused intensively on risk reduction change processes and, to a lesser extent, on mental health needs of persons with human immunodeficiency virus (HIV) conditions. Although research to date has yielded important findings for primary prevention efforts and has identified some psychological dimensions relevant to mental health interventions, there is a pressing need for much more systematic intervention outcome research in both the prevention/behavior change and emotional coping areas. Progress in these areas will be facilitated by better linkage of intervention approaches to behavioral theory; identification of intervention elements that produce HIV risk behavior change; evaluated field-testing of promising intervention models; continued focus on populations that remain at risk (such as gay men and injection drug users); and expansion of prevention efforts to urban, poor, and minority populations increasingly threatened as AIDS/HIV enters a "second wave." Although AIDS is still a relatively new problem, existing behavioral medicine conceptual models and intervention strategies can be adapted to meet the enormous challenges created by AIDS and HIV infection. PMID- 1506506 TI - Recent advances in the assessment and treatment of insomnia. AB - Persistent insomnia has multiple potential causes such as medical, pharmacological, life-style, personality, and behavioral factors. Although many poor sleepers use hypnotic medications, a wide array of cognitive-behavioral interventions are available that target somatic and cognitive arousal, dysfunctional thoughts, and learned maladaptive sleep habits. Outcome research conducted over the past decade reveals that the single treatments of stimulus control and sleep restriction produced the best results, reducing self-reported target complaints by 50-60%. Approximately half of insomniacs show reliable change although only about one third become good sleepers. Multicomponent methods offer considerable promise but on the whole have not surpassed results achieved with the simpler stimulus control. Recommended new directions of pursuit include (a) examination of a broader range of insomnia sufferers, (b) use of multimodal assessment and more objective verification of self-reported benefits (c) research on treatments tailored to individual causal and maintaining factors, and (d) further scrutiny of newer interventions like sleep restriction and more comprehensive multifaceted strategies. PMID- 1506507 TI - Type A behavior pattern: new perspectives on theory, assessment, and intervention. AB - Research on the Type A behavior pattern (TA) has been plagued by inadequate theory, insensitive assessment, and insufficient interventions. These problems (e.g., using global dichotomous ratings of TA) have contributed to several failures of TA to predict cardiovascular outcomes prompting concern for new approaches. Conceptual models are discussed, such as a transactional model of TA, social cognitive theories (e.g., self-evaluative processes), and associative network theory (e.g., how emotions distort information). The view of hostility as the only pathogenic feature of TA is questioned. The ethnographic gap in TA research is described, and detailed descriptive and experimental case studies are recommended. Profile measures that assess all dimensions of TA are urged along with contextually sensitive multimodal assessments. Unlike results of some correlational studies, controlled TA interventions, although few, have consistently yielded positive results. Study of TA within an expanded conceptual perspective is encouraged, especially controlled experiments and interventions. PMID- 1506508 TI - Behavioral medicine approaches to gastrointestinal disorders. AB - Behavioral research in gastroenterology has grown exponentially over the last decade. Controlled studies demonstrate that psychotherapy, stress management, and hypnosis are effective for irritable bowel syndrome; and behavioral treatments are preferred over medical management for some types of fecal incontinence and vomiting. For peptic ulcer disease, interest in behavioral treatments has declined. However, a new syndrome, functional dyspepsia, is now recognized, in which ulcerlike symptoms occur without ulcer and frequently in association with psychological symptoms. For inflammatory bowel disease, stress management training has produced inconsistent outcomes. Newly recognized disorders for which behavioral treatments are needed include constipation associated with inability to relax the pelvic floor muscles during defecation, functional rectal pain (proctalgia), noncardiac chest pain, and aerophagia (excessive air swallowing). PMID- 1506509 TI - Exercise in behavioral medicine. AB - Research on the preventive and rehabilitative applications of exercise and literature on exercise adherence from the past 10 years are briefly reviewed. Although there is now substantial evidence that a low level of physical activity is associated with decreased life expectancy for both men and women and contributes independently to the development of many prevalent chronic diseases, most adults and children lead sedentary lives. Recent intervention studies suggest exercise adherence can be improved in a variety of populations. Researchers in the next decade should continue to elaborate the population- and disease-specific effects of physical activity and exercise and give priority to the problem of exercise adherence, which limits the effectiveness of exercise interventions and remains a significant challenge to behavioral medicine. PMID- 1506510 TI - Psychological factors in rheumatoid arthritis. AB - This article provides a review and discussion of recent developments in psychological research related to rheumatoid arthritis (RA). A description of the medical aspects of the disease is followed by an overview of the literature relating psychological variables to pain and disability in RA; a summary evaluating affective reactions, disease-related beliefs, and coping strategies in RA patients; and a discussion of psychological interventions with this patient population. Methodological weaknesses in the literature are noted and directions for future collaborative research between rheumatologists and psychologists are suggested. PMID- 1506511 TI - Major developments in behavioral diabetes research. AB - Over the past decade, there has been a major increase in behavioral diabetes research. This review focuses on 6 areas: self-treatment, psychosocial impact, diabetes-specific assessment, psychological stress, weight loss intervention, and neuropsychological effects. There has been great progress in identifying factors that predict self-treatment behaviors and psychological adjustment. This research has produced a number of diabetes-specific assessment tools. Psychological stress appears to affect both the etiology and the control of diabetes, but underlying mechanisms remain unclear. Weight loss studies demonstrate the potential benefits of behavioral interventions for diabetes management. Both acute and chronic abnormalities in diabetic blood glucose cause neuropsychological impairments and may cause permanent deficits. The challenge for the next decade is to translate these findings into interventions that improve quality of life and physical well being for individuals with diabetes. PMID- 1506512 TI - Psychological approaches to the treatment of asthma. AB - Outcome literature on psychological treatment for asthma covers psychoeducational self-management programs, relaxation therapy, biofeedback, and family therapy. Psychoeducational approaches now being standardized in a national program are cost-effective. They produce improved adjustment, increased medication compliance, greater perceived self-competence in managing symptoms, and decreased use of medical services. Significant effects have been found for relaxation therapy, although it is not clear whether the effectiveness depends on whole-body relaxation or specifically facial- or respiratory-muscle relaxation. Family therapy is helpful to some asthmatics. Active components in these methods remain to be identified as do the populations whom they can best serve. Biofeedback for respiratory resistance, trachea sounds, and vagal tone shows promise but has not been given adequate clinical testing. PMID- 1506513 TI - Axon populations in cat lingual and chorda tympani nerves. AB - The lingual and chorda tympani nerves from five cats were examined so that normal axonal populations could be determined. After perfusion fixation, the chorda tympani and lingual nerves were removed and processed, and sections were taken from individual and combined nerves for both light and electron microscopy. The chorda tympani remained as a distinct group of smaller axons for at least 4 mm distal to its junction with the lingual nerve. The mean number +/- S.D. of myelinated axons in the chorda tympani central to the junction was 1322 (+/- 268) and in the lingual nerve central to the junction, 3227 (+/- 510). The counts were not significantly different distal to the junction, and there were no side-to side differences. Mean myelinated axon circumferences were significantly smaller in the chorda tympani (12.86 +/- 0.87) than in the lingual nerve (22.79 +/- 1.99; p less than 0.01). The mean size of axons in the chorda tympani was slightly but consistently larger on the left (13.1 +/- 0.73) than on the right side (12.61 +/- 1.01; p less than 0.05). Distal to the junction, the average proportion of non myelinated axons was 44% in both chorda tympani and lingual nerves. PMID- 1506514 TI - Effect of calcium in model plaque on the anticaries activity of fluoride in vitro. AB - The uptake of calcium by a polysaccharide (agarose) gel used as a model for plaque from a two-step treatment (consisting of a calcium rinse followed by a fluoride treatment) and the effect of the deposited calcium in model plaque on caries lesion formation in enamel were determined. Calcium uptake was measured by treatment of the model plaques with [45Ca]-CaCl2 solutions with or without NaF. A two-step treatment consisting of calcium followed by fluoride produced a 100% increase in calcium content of model plaque, presumably due to the formation of CaF2, compared with a treatment with artificial saliva followed by calcium alone. The effects of these increased plaque minerals on caries lesion formation were studied by subjecting model-plaque-covered enamel blocks to a cyclic demineralization-remineralization treatment. Artificial-plaque-covered enamel blocks were treated daily with 180 ppm calcium for ten min, then 100 ppm fluoride for ten min, followed by demineralization for 16 h, and finally, remineralization for seven h and 40 min. After five days, the blocks were sectioned, and lesion formation was determined by microradiography-microdensitometry. Artificial plaque treated with a calcium rinse followed by a fluoride rinse reduced lesion size by 90%, compared with a 68% reduction by a fluoride rinse alone. When the experiment was repeated with a simulated pre-brush calcium rinse (180 ppm calcium) followed by a fluoride dentifrice suspension (110 ppm fluoride), lesion size was reduced by 46%, compared with a 32% reduction by the fluoride dentifrice suspension alone. PMID- 1506515 TI - Effect of age on the rate of tooth movement in combination with local use of 1,25(OH)2D3 and mechanical force in the rat. AB - The purpose of this study was to compare the amount and rate of tooth movement in young and mature rats administered 1,25(OH)2D3 simultaneous with application of mechanical force. In 30 seven-week-old and 30 28-week-old male Wistar rats, the right maxillary first molar was moved buccally with a fixed appliance. The appliances delivered forces ranging from 5 to 20 g. Twenty microL of 1,25(OH)2D3 (10(-10) and 10(-8) mol/L) was injected locally into the submucosal palatal area of the root bifurcation of the right first molar. The left side was injected with phosphate-buffered saline (PBS). In young rats receiving 10(-10) mol/L 1,25(OH)2D3 every three days, tooth movement significantly increased to 126% of that in PBS-injected control rats on day 20. In 1,25(OH)2D3-injected mature rats, tooth movement was stimulated markedly and increased with 10(-10) mol/L to 245% and with 10(-8) mol/L to 154% of the amount of tooth movement seen in the PBS injected controls by the end of the experiment. PBS-injected rats had a plateau stage where tooth movement did not occur at all, while there was no such lag-time in the 1,25(OH)2D3-injected group which showed continuous tooth movement. The local injection of 1,25(OH)2D3 did not change serum calcium, phosphate, and alkaline phosphatase activity, and there were no apparent clinical or microscopic side-effects. PMID- 1506516 TI - Solubilization of dentin matrix collagen in situ. AB - The effects of the oral environment on dentin matrix collagen were studied. In the partial prostheses of 12 participants, two completely demineralized dentin specimens were mounted covered by a Dacron gauze. After an experimental period of seven weeks, the specimens were transferred to a trypsin-containing buffer for determination of the amount of denatured collagen. Subsequently, the specimens were incubated with a bacterial collagenase for assessment of the amount of collagen. After the intra-oral exposure, there was a collagen loss varying between 1 and 47 wt%. This variation might be due to differences in proteolytic activity of the colonizing microflora. After exposure to the oral environment, only about 0.5 wt% of the available collagen was trypsin-degradable. This indicates a rapid solubilization of the denatured collagen from the specimens into the oral cavity. A separate group of specimens was examined by light microscopy and transmission electron microscopy. Various degrees of breakdown could be discerned. Some experimental specimens showed loss of surface integrity and tubules heavily infected with different types of micro-organisms. The lumens of the tubules were enlarged, sometimes creating caverns as a result of the loss of the intertubular collagenous matrix. PMID- 1506517 TI - Determination and selection of the optimum number of sites and patients for clinical studies. AB - Calculating required sample sizes is a critical step in the design of any study. For dental studies, the sample size needs to be specified at two levels: (1) the number of patients (n) enrolled in the study, and (2) the average number of sites (m) examined per patient. In general, m and n should be selected in such a way that the precision of the research findings is maximized, while the cost of the study is minimized. This objective can be realized by taking stock of the components of variation and the costs involved with enrolling patients and examining sites. The research cost for n patients ($C1/patient), at an average of m sites per patient ($C2/site), can usually be approximated by nC1 + nmC2. The precision varies as a function of the variance components, m, and n. To optimize precision for a fixed cost, the average number of sites examined per patient (m(opt)) should be approximately equal to [formula: see text] where rho is the within-patient correlation coefficient of the site-specific variable measured. When m(opt) is approximately equal to or in excess of the average number of sites available per patient, whole-mouth examinations are indicated. When m(opt) is considerably smaller than the average number of sites available, the sample of optimum size should be obtained by some random mechanism. Examination of a number of sites considerably different from m(opt) results in a waste of resources, regardless of the number of patients studied. Standard statistical analyses for determination of the patient sample size required to obtain a pre-specified precision or power are discussed. PMID- 1506518 TI - Chewing pressure vs. wear of composites and opposing enamel cusps. AB - The effects of various chewing pressures on the wear of composites and enamel were assessed in vitro. Standardized composite discs (8 mm in diameter, 2 mm in height) were made of a fine-particle hybrid (FPH), a coarse-particle hybrid (CPH), and a homogeneous microfilled composite (HMC). The composite specimens were chemically degraded by immersion in 75% ethanol for 24 h, brushed for 30 min, and then thermocycled 300 times (5-55-5 degrees C) while being occlusally loaded 120,000 times at 1.7 Hz, with chewing forces of 25, 50, 75, and 100 N. Standardized human enamel cusps with a uniform contact area of 0.384 mm2 served as antagonists in the chewing machine. Wear of the composites and enamel cusps, their combined wear, and the increase of the enamel contact surfaces were quantified. An increase in chewing pressure significantly enhanced the wear of both composite and enamel in all groups except for the antagonists opposing a HMC. The FPH was most wear-resistant to in vitro chewing pressures in the range of 6.58 to 19.74 MN/m2, the CPH at 26.32 MN/m2, while the HMC was the most enamel friendly of the three composites tested. The FPH composite had the least disintegration in the occlusal contact area. The ranking of the composites generally varied at the different chewing pressures with respect to the three types of quantified wear--that is, composite wear, enamel wear, and total wear. PMID- 1506519 TI - Morphological aspects of the resin-dentin interdiffusion zone with different dentin adhesive systems. AB - Cross-sections of resin-dentin interfaces were etched with an argon-ion beam to make their substructure detectable by scanning electron microscopy. The dentin adhesive systems were categorized morphologically into three groups, and an attempt was made to clarify their adhesive mechanism. The first group of products removed the smear layer. The argon-ion bombardment clearly disclosed a hybrid or resin-impregnated dentin layer. It is hypothesized that conditioning with acidic or chelating agents demineralized the dentin surface-layer to a certain depth, leaving behind a collagen-rich mesh-work. Hydrophilic monomers are then believed to alter this collagen-fiber arrangement in a way that facilitates penetration of the adhesive resin, resulting in a mechanical, intermingled link between collagen and the adhesive resin. The second group preserved the smear layer. In this case, the dentinal tubules were obliterated with globular particles at their orifices and remained patent underneath these smear plugs. This type of adhesive system aims at the incorporation of the smear layer into the hydrophilic monomers, which have an affinity for the organic and/or inorganic components of the underlying dentin. Finally, a third, small group only partly dissolved the smear layer, creating a thin resin-impregnated dentin layer and a resin-impregnated smear plug. This study clearly showed that the application of recent adhesive systems induced structural changes in the dentin surface morphology, creating a retentive interface, called the inter-diffusion zone, between the deep, untouched dentin layers and the composite filling material. This resin-dentin interdiffusion zone offers bonding sites for copolymerization with the resin composite and, concurrently, might have protective potential for the pulp tissues. PMID- 1506520 TI - Conference report: materials research in maxillofacial prosthetics. PMID- 1506521 TI - Pit-and-fissure sealants: a global lack of science transfer? PMID- 1506522 TI - Characterization of external ear impulse responses using Golay codes. AB - This report explains the use of a complementary series, Golay codes, for probing the impulse response of the external ear. The codes are used to measure both the resonance of the human ear canal, using a sealed sound-delivery system, and to measure the transfer function of the pinna, using a free-field source. With two series of 512 binary numbers, the improvement in signal-to-noise ratio over a single impulse approaches the theoretical value of 30.1 dB [10 log(2.512)]. This technique has many of the same properties as maximal-length sequences [M. R. Schroeder, J. Acoust. Soc. Am. 66, 497-500 (1979)], but it has the added advantage that the sequence length is an integer power of two and is, therefore, particularly convenient to use with modern Fourier transform techniques. PMID- 1506523 TI - Lack of association between otoacoustic emissions and hearing difficulty in subjects with normal hearing thresholds. AB - Evoked otoacoustic emissions (EOAE) are a sensitive indicator of subtle cochlear damage and hence might explain why some people complain of excessive difficulty understanding speech in a background of noise, despite having normal hearing thresholds. This phenomenon has been termed "Obscure Auditory Dysfunction" (OAD). Recorded EOAE waveforms from a group of 50 OAD patients were compared with those from a group of 50 matched controls. No significant difference could be found between the two groups across a range of objective and subjective descriptors of the EOAEs. Any cochlear component of OAD does not appear to affect the function of the outer hair cells sufficiently to modify EOAEs materially. PMID- 1506524 TI - Ultrasonic attenuation in articular cartilage. AB - Previous studies have utilized articular cartilage from joints as a model to investigate the influence of various constituents in a connective tissue matrix on ultrasonic properties. These studies have assumed a degree of homogeneity of articular cartilage taken from the same joint. However, tactile loads on articular cartilage vary significantly with location in a joint, and the effects of mechanical load on the connective tissue matrix and the resulting effects on ultrasonic properties are not known. This work reports the variations in acoustical properties of bovine articular cartilage from the stifle (knee) joint both among different joints and within each joint. A pulse-echo transmission technique was used to measure acoustic attenuation in the frequency range of 10 to 40 MHz. The attenuation coefficient was characterized by the integrated attenuation (mean value) over the frequency bandwidth considered. Integrated attenuation averaged over each joint varied among joints from 3.2 to 7.5 NP/cm (6.0 +/- 2.0, mean +/- s.d.). Additionally, a linear regression (r = 0.59) of all the data versus location along the patellar groove indicated that within joints integrated attenuation increased from proximal to distal locations by 6% to 60% (32 +/- 25, mean +/- s.d.). The variations observed among joints and along the patellar groove within a given joint suggest that studies utilizing articular cartilage to determine the role of connective tissue constituents on acoustic properties require control for joint and location. An additional outcome of this study was the observation that damage to the load-bearing surface of articular cartilage may be detectable ultrasonically through characteristics of the acoustic reflection from the articular surface. PMID- 1506525 TI - Inferring articulation and recognizing gestures from acoustics with a neural network trained on x-ray microbeam data. AB - This paper describes a method for inferring articulatory parameters from acoustics with a neural network trained on paired acoustic and articulatory data. An x-ray microbeam recorded the vertical movements of the lower lip, tongue tip, and tongue dorsum of three speakers saying the English stop consonants in repeated Ce syllables. A neural network was then trained to map from simultaneously recorded acoustic data to the articulatory data. To evaluate learning, acoustics from the training set were passed through the neural network. To evaluate generalization, acoustics from speakers or consonants excluded from the training set were passed through the network. The articulatory trajectories thus inferred were a good fit to the actual movements in both the learning and generalization conditions, as judged by root-mean-square error and correlation. Inferred trajectories were also matched to templates of lower lip, tongue tip, and tongue dorsum release gestures extracted from the original data. This technique correctly recognized from 94.4% to 98.9% of all gestures in the learning and cross-speaker generalization conditions, and 75% of gestures underlying consonants excluded from the training set. In addition, greater regularity was observed for movements of articulators that were critical in the formation of each consonant. PMID- 1506526 TI - Native language factors affecting use of vocalic cues to final consonant voicing in English. AB - Preceding vocalic information can cue final consonant voicing for native English speakers. This study examines subjects' use of two vocalic cues, vocalic duration, and F1 offset frequency, as a function of two native language factors, experience with final stop consonants, and experience with phonemic vowel length. Native speakers of English are compared to native speakers of Japanese and Mandarin Chinese who are learning English as a second language. Experiment 1 measured the F1 offset frequency and vocalic duration in productions of "pod" and "pot." Experiment 2 assessed identification of natural tokens of "pod" and "pot" with and without closure segments and bursts. Experiment 3 assessed categorization of synthetic "pod"-"pot" stimuli that systematically manipulated vocalic duration and F1 offset frequency. Native speakers of English showed the strongest implementation of and sensitivity to vocalic duration, Mandarin speakers showed significantly weaker effects, and Japanese speakers fell in between. Group-related differences in use of F1 offset frequency were smaller, and much clearer in the case of production than perception. It is hypothesized that a lack of experience with final consonants penalizes use of vocalic cues among the Japanese and Mandarin subjects, in general. The advantage of the Japanese subjects for use of vocalic duration further suggests a facilitation effect of experience with phonemic vowel length. PMID- 1506527 TI - Phonetic prototypes: influence of place of articulation and speaking rate on the internal structure of voicing categories. AB - In this investigation, the effects of context on the perception of voicing contrasts specified by voice-onset-time (VOT) in syllable-initial stop consonants were examined. In an earlier paper [J.L. Miller and L.E. Volaitis, Percept. Psychophys. 46, 505-512 (1989)], it was reported that the listener's adjustment for one contextual variable, speaking rate, was not confined to the region of the phonetic category boundary, but extended throughout the phonetic category. The current investigation examines whether this type of perceptual remapping also occurs for another contextual variable, the place of articulation of the syllable initial consonant. In a preliminary experiment that involved acoustic measurement of natural speech, it was confirmed that as place of articulation moves from labial to velar, VOT increases, and it was established that this occurs across a range of speaking rates (syllable durations). In the main experiments, which focused on the voiceless category, it was found that this acoustic change was reflected in perception not only as a shift in the location of the voiced voiceless category boundary, but also a change in both the specific range of stimuli identified as members of the voiceless category and the set of stimuli judged to be the best exemplars, or prototypes, of the category. These findings extend earlier research by showing that a change in place of articulation, like a change in speaking rate, systematically alters the internal perceptual structure of voicing categories. PMID- 1506528 TI - Acoustic measures for linguistic features distinguishing the semivowels/wjrl/in American English. AB - Acoustic properties related to the linguistic features which characterize the semivowels in American English were quantified and analyzed statistically. The features can be divided into those which separate the semivowels from other sounds and those which distinguish among the semivowels. The features of interest are sonorant, syllabic, consonantal, high, back, front, and retroflex. Acoustic correlates of these features were investigated in this study of the semivowels. The acoustic correlates, which are based on relative measures, were tested on a corpus of 233 polysyllabic words, each of which was spoken once by two males and two females. For the most part, the appropriate distinctions are made by the chosen acoustic properties for features. However, for each property, there was some overlap in the acoustic correlates of features for the sounds being distinguished. An examination of the sounds in the overlap regions reveals that their surface manifestation varies substantially from the canonical form. In large part, the observed variability can be explained in terms of changes due to feature spreading and lenition. PMID- 1506529 TI - A cognitive influence on the loudness of tones that change continuously in level. AB - The loudness of tones that change continuously in level over time was studied using magnitude estimation and a delayed loudness-balance procedure. In the magnitude estimation task, subjects estimated the loudness of continuous and intermittent 1000-Hz tones that either increased or decreased continuously in level over roughly 3 min. Two stimulus ranges were used: 30 to 70 and 50 to 90 dB SPL. For the low-level conditions, the results are essentially identical to those of Canevet and Scharf [J. Acoust. Soc. Am. 88, 2136-2142 (1990)], who ran similar conditions. Tones that increased in level changed in loudness as a function of SPL at a slower rate than tones that decreased in level. For the high-level conditions, the same result was obtained, but the magnitude of the difference among conditions is smaller. A delayed loudness-matching procedure was used to measure the physical magnitude corresponding to loudness differences among a subset of the conditions. Judged equal-loudness levels showed a sharp decline in loudness for conditions with tones that decreased continuously in level, but the magnitude of the reduction was less than that interpolated from magnitude estimates for identical stimuli. The source of the difference is unclear. To explore the role of cognitive influences, subjects' attention was diverted by a video word-identification task during the period of adaptation. For this task, the loudness decline was reduced for loudness balances and magnitude estimations compared to conditions where attention was concentrated on the adapting stimulus. In another magnitude-estimation task, the loudness decline for monaural stimulation was found to occur only in the "adapted" ear.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1506530 TI - Dynamic frequency change among stimulus components: effects of coherence on detectability. AB - Experiments were performed to determine the effect of coherent dynamic frequency change among stimulus components on detection of one of those components. Detectability of a frequency glide signal, centered at 660 Hz, was measured in the presence of two additional frequency glides centered at 220 and 440 Hz. Results show that the signal is most difficult to detect when it is changing coherently with the other stimulus components, and that detectability gradually improves as the frequency change among stimulus components becomes less coherent. A control experiment indicated that detectability of the signal is influenced somewhat by the average spectral distance between the signal and the other stimulus components. In order to separate the effects of dynamic frequency change from those of altering harmonic relationships, the experiment was repeated with stimulus components not harmonically related. Results are similar in pattern, though with somewhat smaller shifts. A final experiment was performed to determine if the observed shifts in detectability might be due to changes in the maximum spectral distance between signal and masker when their frequencies are changing incoherently. Results of this experiment indicate that detectability improves when frequency change of signal and masker is not coherent, even when maximum spectral distance does not change. These data indicate the likelihood that the auditory system is able to use coherent dynamic frequency change among stimulus components. PMID- 1506531 TI - Auditory filter bandwidths as a function of level at low frequencies (125 Hz-1 kHz) AB - Auditory filter bandwidths were measured using the symmetric notched-noise method in five normally hearing listeners at four masker levels (40-70 dB SPL/Hz in 10 dB steps) and four probe frequencies (125-1000 Hz in octave steps). Accurate stimulus spectrum shape and level were ensured by use of a headphone monitoring technique. Auditory filter bandwidths decreased with decreasing frequency from 1 kHz down to 125 Hz. On the whole, bandwidths increased with increasing level, but the effect of level on bandwidth was greater as frequency increased, with little or no effect of level at 125 Hz. Insofar as the results from the notched-noise method reflect basilar membrane vibration patterns, basilar membrane mechanics appear to become less nonlinear as one approaches the apex of the cochlea. PMID- 1506532 TI - Intensity discrimination in forward masking. AB - A nonmonotonic intensity discrimination function was recently reported in which a midlevel hump occurred for 25-ms sinusoidal standards ranging from 20 to 100 dB SPL and presented 100 ms after an intense narrow-band noise forward masker [F.-G. Zeng et al., Hear. Res. 55, 223-230 (1991)]. This paper provides additional data on how the midlevel hump is affected by three factors of forward masking: signal delay, masker level, and frequency. Specifically, just-noticeable differences (jnd's) in intensity were obtained at signal delays of 50, 200, and 400 ms. Results show that at the midlevels the forward-masked intensity jnd's did not recover to their unmasked values, even at the 400-ms signal delay. The longer the signal delay, the smaller this midlevel hump. This slow recovery of the midlevel jnd's is consistent with the finding that low-spontaneous rate (SR) neurons have a slow recovery from forward masking [E. M. Relkin and J. R. Doucet, Hear. Res. 55, 215-222 (1991)]. The large midlevel effect decreased sharply as masker level was reduced from 90 to 60 dB SPL, and disappeared for masker levels less than 40 dB SPL. A frequency selectivity effect for the large midlevel jnd effect was also observed, as maskers with frequency components 2 to 3 oct away from the signal frequency did not affect the jnd's. Overall, the present data are consistent with the hypothesis of Zeng et al. (1991) that low-SR neurons are involved in the midlevel hump of intensity discrimination in forward masking. PMID- 1506533 TI - On the consistency of tapping to repeated noise. AB - Repeated noise at 1-4 cycles per second evokes an effortless heard rhythmic sensation which is often heard as "clanks" and "rasping." Tapping in synchrony with the period of the perceived structure is easy and consistent within one presentation. The present study addresses the question of whether the tapping to presentations at different times is consistent across presentations and across subjects. Nine listeners from three countries were presented with repeated Gaussian noise samples in 300 separate cyclical presentations. Nine samples of Gaussian noise with sample lengths ranging from 500 to 700 ms were used. In each of the presentations, one of these samples was selected at random and presented cyclically with transientless juxtapositions. The listeners were instructed to tap in synchrony with the perceived structure (i.e., once per period). Tapping to later presentations of a given sample was found to be consistent with prior tapping to the same sample: In most cases, one or two different tapping points per noise sample could be reproduced in different presentations. In the case of two possible tapping points in different presentations, the two points are usually far away from each other (most likely half a period away). The correlation between subjects is noticeable, although not perfect. The correlation between subjects of the same country is not significantly higher. The noise generating algorithm is given explicitly to allow subsequent studies to use exactly the same noises. PMID- 1506534 TI - Use of sound-pressure level in auditory distance discrimination by 6-month-old infants and adults. AB - Six-month-old infants have been found to respond differentially to sounding objects placed within reach and beyond reach when no visual cues were available. The goal of the present study was to investigate whether sound-pressure level (SPL) serves as an auditory cue in distance discrimination. Thirty-two 6-month olds were presented with recordings of sounding objects first in the light at midline position, then in the dark at 45 degrees to the right and left. On half of the dark trials the object was near (15 cm), and on half it was far (100 cm). For the control group the near sound was naturally 7 dB louder than the far. The experimental group had SPL counterbalanced across near and far locations to provide an inconsistent cue. Measures of infant reaching were scored from videotape. Two groups of adults were run under similar conditions; adults were tested on reaching as well as verbal reports of distance judgment. All infants reached more for the near object, regardless of the sound's SPL, suggesting that infants did not rely on this as a major distance cue. In contrast, adults' verbal judgments of distance were based heavily on SPL, a strategy that produced higher error rates in the group with SPL counterbalanced across distance. A followup study in which adults were instructed to move their heads before judging the sound's distance did not support the hypothesis that infants' head movements were responsible for their overcoming the misleading SPL information. PMID- 1506535 TI - Attenuation of sound by schooling fish. AB - Attenuation of sound by schooling fish was measured or estimated for yellowtail (Seriola quinqueradiata), sea bream (Pagrus major), and spotted mackerel (Scomber australasicus) in culture nets and a net cage. The results, along with those of other researchers, are normalized to obtain extinction cross sections per 2/3 power of the body weight. In the normalized cross sections there are no large differences among fish species, sizes, and measuring methods. The attenuation increases slightly with the frequency. Attenuations to be encountered in field observations by echo sounders are estimated and the results reveal that ordinary fish schools do not attenuate sound significantly. PMID- 1506536 TI - Career patterns and job satisfaction of Canadian nurse educators. AB - The purpose of this study was to describe the career patterns and job satisfaction of Ontario university and college nurse educators. A descriptive survey design was employed using mailed questionnaires. The sample comprised 60 nurse educators, 30 from three universities and 30 from three colleges. Forty four returned the completed questionnaire, giving a response rate of 73%. The variables about the career patterns and goals of the nurse educators included their past and present job satisfaction. Career patterns were described as stable, double-track, interrupted and unstable. Similarities and differences were compared and described in relation to these factors. Significant differences in job satisfaction were found between university and college faculty on nine of the 36 job characteristics (for example, leadership style, independence, autonomy and salary). There were no significant differences in job satisfaction for each of the career patterns and the selected demographic variables of age, years in nursing education, educational level and salary between the university and college faculty. PMID- 1506537 TI - Janforum: locus of control theory. PMID- 1506538 TI - Marjorie Simpson: pioneering British nurse researcher. PMID- 1506539 TI - Client-public health nurse relationships in child health care: a grounded theory study. AB - Client-public health nurse relationships are considered to be important in nursing literature. However, little research in nursing has touched this area. The purpose of this paper is to describe a study of the patterns of interaction in terms of relationships between clients (mother and child under 1 year of age) and public health nurses in child health care at Finnish health centres. The qualitative data were collected by observing client-public health nurse interactions during visits. In total, 1554 interactions were observed over 2 years from 20 visits to child health centres. The grounded theory method was used in this study. Various relationships were identified between child and mother, child and public health nurse and mother and public health nurse. The relationship between child and mother during the visit was called a tender, protective and persuasive relationship. The relationship between child and public health nurse was called a persuasive and entertainment relationship. The main relationship between mother and public health nurse was called relationship supporting self-confidence. Suggestions for nursing practice and further research are made. PMID- 1506540 TI - Middle-Eastern immigrant parents' social networks and help-seeking for child health care. AB - The purpose of this research was to describe: (a) Arab-American immigrant parents' perceptions of their social networks, including social support; and (b) Arab-American immigrant parents' perceptions of their help-seeking related to child health care. Seventy-three immigrant parents who were Egyptian-American (n = 17), Palestinian-American (n = 44) and Yemeni-American (n = 12) completed the Norbeck Social Support Questionnaire, four Supplementary Social Support Questions, a Support System Map and a Child Health Interview Guide. Family and relatives were perceived as the major source of support and comprised the highest percentage of social network members. Compared with published scores of a normative American sample, the immigrant parents' scores were lower (P less than 0.01) on all social network and social support variables. There was a moderate negative correlation (r = 0.47) between parents' number of years of residence in the USA and percentage of network members living outside the USA (P less than 0.01) and a weak positive correlation (r = 0.36) between number of years in the USA and percentage of network members living close to the parent (P less than 0.01). Parents' help-seeking for child health care involved use of a variety of resources, with reliance on some long-distance support from family in the Middle East. This descriptive research provides a basis for further research on patterns of support and help-seeking in immigrant parents. PMID- 1506541 TI - The non-existence of non-compliant families: the influence of Humberto Maturana. AB - Non-compliance is not only an epistemological error but a biological impossibility. This profound statement arises from the influence of Humberto Maturana's revolutionary meta-theory of cognition. The definitions and significant implications of two major theoretical concepts of this meta-theory of cognition, namely structural determinism and objectivity-in-parenthesis, are discussed. These radical concepts challenge the approved North American Nursing Diagnostic Association's nursing diagnosis of non-compliance. Maturana's theory reveals the impossibility of instructive interaction, leading the authors to conclude the non-existence of non-compliant families. PMID- 1506542 TI - Suffering: a relatively unexplored phenomenon among family caregivers of non institutionalized patients with cancer. AB - Suffering is a phenomenon with physical and emotional components. Although several studies have drawn attention to the needs of, and demands placed on families who provide care for patients with a diagnosis of cancer at home, few have discussed the suffering which many of these caregivers experience. This paper will illustrate the phenomenon of suffering as seen in the responses made by family caregivers of patients with cancer. Eighty-three family caregivers drawn from a probability sample of patients with a diagnosis of cancer were interviewed in their homes to determine needs they encountered in their caregiving roles. The caregivers consisted of 43 males and 40 females, with mean ages of 53 and 54 years respectively. Families not only identified their needs, they also indicated several areas which were for them sources of suffering. The findings revealed that family suffering often stemmed from fear of loneliness; uncertainty about the future (their own and that of the patients); lifestyle disruption; communication breakdown; lack of support; and their sense of helplessness. These findings suggest that health professionals, particularly nurses, who work with families in their homes, must be alert and sensitive to cues and circumstances which could indicate suffering, and in so doing, take the necessary steps to ameliorate their situation. PMID- 1506543 TI - Effectiveness and cost efficiency of interventions in health promotion. AB - The effect of a stress management programme as a component of an overall fitness programme was evaluated. Psychological, physiological and economic parameters were examined in relation to stress management activities in an experimental study. Subjects were stratified by life stressors and then randomly assigned to groups. Stress-related physical symptoms decreased significantly (P less than 0.05) in the treatment group. Those who practised the relaxation techniques regularly had significantly lower systolic blood pressure (P less than 0.05). Results of cost evaluation demonstrate the benefits from a programme with relatively low overall costs. PMID- 1506544 TI - Coping: an essential element of nursing. AB - How well a person copes is central in determining his or her well-being, no matter how ill he or she is. Without an accurate appreciation of what coping is and how it may be facilitated, attempts to help patients may be both ineffective and harmful. But the subject is multifaceted and poses many problems for clinicians and researchers alike. This paper attempts to synthesize available knowledge on coping from various disciplines and apply it to life as nurses know it. PMID- 1506545 TI - The drama of nursing. AB - This exploratory paper considers a few possibilities for conceiving nursing as a form of aesthetic praxis. More specifically, drawing on the works of Erving Goffman on dramaturgy, and Elizabeth Burns on theatre, it makes some suggestions concerning nursing as a form of dramatic performance, and briefly attempts to relate this to concepts of praxis drawn from the writings of Hannah Arendt and critical social theorists. In contrast to Goffman's dramaturgy, which stresses the artifice of social relations and suggests a cynical view of human interactions, a critical theory of dramatic praxis introduces a normative dimension in which performance may become self-realizing and emancipatory as it aspires to the status of aesthetic praxis. Conceived in such terms, nursing practice becomes a powerful form of self-expression which has the potential to become liberating for the nurse and the patient. PMID- 1506546 TI - The nature of dilemmas in dialysis nurse practice. AB - Dilemmas are a part of nurse practice. In situations where a problem potentially has two or more unsatisfactory resolutions, the nurse chooses which course of action to take. The decision to choose constitutes a dilemma. This study focuses on the dilemmas faced by nurses in dialysis units and the context in which they occur. A qualitative design was employed, using open interviews with eight nurses currently employed in dialysis nursing. This approach was taken in order to explore and gain in-depth understanding of the dilemmas in practice. Analysis reveals that dilemmas encountered in dialysis nursing emerge from conflicts in relationships with other people in the work environment. The dilemmas relate to the nurses' perception of the limited power they have in the determination of their practice. This powerlessness is reinforced by their perceived and real isolation from nurses working outside their area of practice. Traditionally, literature on dilemmas in nursing has focused on the development of ethical frameworks to guide practice and the resolution of dilemmas. However, the findings of this study suggest that if nurses are to deal with dilemmas effectively, both for the nurse and the patient, there must be an examination of the structural constraints affecting their practice. Models that are employed by nurses to guide practice must account for the structural elements in the work environment. PMID- 1506547 TI - Patient satisfaction with care in the emergency department. AB - This paper looks at the patient satisfaction levels with care in an emergency department (ED) setting. Specific aspects of nursing care, information given to patients, auxiliary personnel and ED environment are examined in the light of the current literature on the subject. Recommendations for practice are provided to assist the nurse and administrator in updating their accountability to the ED patient. PMID- 1506548 TI - Quality of life as quality of being: an alternative to the subject-object dichotomy. AB - The opening section of this paper is concerned with certain questions concerning the concept 'quality of life'. Is it possible for one person to make judgements about the quality of life of another? If it is possible, then is it morally acceptable? Given that quality of life is a concept and therefore not amenable to direct observation, which visible phenomena will be chosen as its indicators, and how can their choice be justified? Do the components of a life of quality vary from person to person, or can features be identified which are common to all? Next, it is argued that instruments which have been developed to measure quality of life give clues to the ontological beliefs of their authors; those which address fragments of the human experience, or accept the artificial limits of the subjective/objective dichotomy, are expressive of a fractured and reductionist view of what it means to be a human being. Finally, it is suggested that the adoption of insights drawn from Heidegger's work would enable us to develop a rather more unified view of quality of life as quality of being, and that this theoretical principle might constitute a common link between nurses of varying professional backgrounds. PMID- 1506549 TI - Labelling students in nursing. AB - This paper is concerned with the factors which can lead to the labelling of students in nursing. It commences with some of the considerations involved when one elects to enter a profession. This is examined in the light of changing ideologies about the ways in which it is believed that nurses should be taught and whether teaching aims to train or educate nurses. This analysis is applied to the issues that arise in terms of labelling students, and the possible subsequent effects on the students' capacity to succeed. The continuing dissonance inside the educational environment and between education and clinical practice are proposed as contributory factors in the processes that can lead to student frustration and disenchantment. Finally, some suggestions are made to attempt to address these issues. PMID- 1506550 TI - The relationship between locus of control, instrumental and expressive traits among nurses. AB - The purpose of this study was to explore the relationship between locus of control and sex role orientation among nurses. Ninety-eight participants, working female registered nurses between the ages of 30 and 59, were placed into one of four sex type groups using scores on the Personal Attributes Questionnaire. The groups were then compared to each other using Rotter's Locus of Control Scale. Previous research findings had indicated that women in a traditional female occupation would be sex typed in role orientation and externally locused. The subjects in this study exhibited variability in locus of control and sex role orientation. Locus of control orientation was not related to sex role orientation. The implications of the results were discussed and directions for future research were considered. PMID- 1506551 TI - Facilitator not teacher: a role change for tutors in open learning nursing education. AB - Open learning is now an established, if rapidly changing, part of post-compulsory education and training in the United Kingdom. It has also developed in significant ways within nurse education. A key role in successful open learning is that of the tutor. Differences between the activities of teaching and facilitation are defined and ways of mapping the tutor's role within these are suggested. Differences in approach can be clustered around the topics of: the locus of control; learning methodology; the learning context and media; and the curriculum. These are discussed in turn to elicit what are the key issues for tutoring in relation to each one. PMID- 1506552 TI - Using a manpower database to analyse the nurse limbo stock. AB - A manpower database for nurses employed by the Department of Health and Social Services (DHSS) in Northern Ireland is used to identify the qualified nurses not currently employed by the DHSS, i.e. the limbo stock, and describe this stock in terms of age, sex, length of previous service, grade and location. This information is invaluable for manpower planners who must decide on how many vacancies can be filled by recruitment from the limbo stock, as opposed to training new nurses. Such a methodology provides a valuable tool for the nurse manpower planner. PMID- 1506554 TI - End-of-life issues--a practice perspective. PMID- 1506553 TI - Reading and writing editorials. PMID- 1506555 TI - Regulation of advanced practice nursing--the cog in the health policy engine. PMID- 1506556 TI - Effectiveness and outcomes research--data sources with potential for nursing research. PMID- 1506557 TI - Primary nursing for the 1990s and beyond. PMID- 1506558 TI - Freshmen baccalaureate nursing students' perceptions of their academic and nonacademic experiences: implications for retention. AB - As a component of the evaluation for a program designed to enhance recruitment and retention of disadvantaged nursing students, qualitative interviews were conducted, with a sample of 20 baccalaureate nursing students at the end of their freshman year. Students were asked to describe positive aspects of their academic and nonacademic experiences as well as problems that were experienced, with recommendations for resolving these problems. Positive aspects of the freshman experience that were identified included academic, social, familial, and financial support. Problems cited were related to two categories of factors, external and internal. Problems related to external factors included excessive academic loads, course-specific problems such as with the sciences, large class size, faculty inattentiveness, racial tensions, dorm/roommate problems, and parking or commuting time. Problems related to internal factors included poor study habits, loneliness, homesickness, family conflicts, and difficulties with peer relationships. The findings can be used by nursing faculty to determine the extent to which programs address students' perceived needs and to identify innovative retention strategies that would enhance students' perceptions of their college experience. PMID- 1506559 TI - Spiritual well-being: a predictor of hardiness in patients with acquired immunodeficiency syndrome. AB - This study examined the relationship between spiritual well-being and hardiness in a group of 100 subjects who either tested positive for the human immunodeficiency virus (HIV+) or who had diagnoses of acquired immunodeficiency syndrome (AIDS)-related complex (ARC) or AIDS. Each subject completed the Spiritual Well-Being Scale, the Personal Views Survey (to measure hardiness), and a Demographic Data Survey. Analysis of data included Pearson Product-Moment Correlation Coefficients and multiple regression techniques. The results demonstrated that there was a significant relationship between spiritual well being and hardiness (multiple R = .4165; P less than .001) as well as between the existential component of spiritual well-being and hardiness (multiple R = .5047; P less than .001). The conclusions of the study are that in this sample those individuals who were spiritually well and who were able to find meaning and purpose in their lives were also hardier. This finding has significance for the care that is provided to persons who are HIV+ or who have diagnoses of ARC or AIDS. PMID- 1506560 TI - Refusal to care for patients with human immunodeficiency virus/acquired immunodeficiency syndrome: issues and responses. AB - Nurses historically have accepted the risk of contagion while caring for patients with infectious diseases. The duty to care for patients is directly related to the care the patient requires, the nurse's knowledge, and the extraordinary risk to the nurse. The current infection with human immunodeficiency virus (HIV) and acquired immunodeficiency syndrome (AIDS) highlights other factors, such as fear, ignorance, and homophobia, that influence a nurse's decision to refuse to provide care. Professional associations, nurse administrators, and educators must assist nurses to gain the knowledge and skill necessary to provide care as well as explore feelings about different life-styles. PMID- 1506561 TI - Judgment: the nurse's key to knowledge. AB - Recently, nursing has turned more of its attention to judgment and has given it a high priority for study. A significant part of that study asks: What is judgment? How is it made? Why is it important? The ancient Greeks discovered reason and then created enduring art that demonstrates it. Three nurses are excerpted from this literature to evoke and explain how judgment is made. Euryclea, Cilissa, and Medea's nurse also illustrate the personal commitment in judgment. Human beings depend on the nurse's judgment. They depend on the nurse as knower. Nurses are obliged to move from doubt and opinion towards knowledge and certitude. Judgment is the nurse's key to that knowledge. PMID- 1506562 TI - A statewide consortium initiative to establish an undergraduate clinical internship program. AB - The amount of time and the type of experience needed by undergraduate students in the clinical setting to actually practice nursing has been the subject of many debates between nurses in academe and service. Rather than blaming each other for the culture shock and transition problems of neophyte nurses, members of the academic and practice community in Rhode Island decided to address the problem together. The development of the collaborative program described in this article grew out of a research study and was coordinated through the efforts of nurses from service and academe. The central outcome of this statewide consortium's project was to increase the students' level of nursing competencies. "Turf" issues that related to the colleges and the hospitals involved became secondary. Everyone involved believed that students from different collegiate programs working together presented exciting opportunities to share and learn from one another. In addition, other outcomes included increased recruitment and retention of these baccalaureate-prepared nurses in the hospitals, and greater ease in their orientation and transition. In addition, a cluster of three research studies were conducted by members of the consortium. This ongoing program, in which nurses in education and service are working together in a statewide consortium to break down the turf issues that separated them, is achieving outcomes that could not have been accomplished had it been undertaken independently. This article describes the process used to develop, implement, and evaluate such a program.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1506563 TI - Barriers to health care for Vietnamese refugees. AB - This study was undertaken to determine the dynamics of why Vietnamese refugees may not optimally use existing health services in the United States. A random sample of 75 refugees was interviewed by a bilingual translator. Multivariate analysis of variance was used to analyze the effects of time of arrival on whether the following are barriers to care: not having a translator available in health care facilities, feeling understood by health care providers, being able to understand the written and verbal instructions of providers, and not having a primary provider. The hypothesis, that time-of-arrival groups would differ significantly on these variables, was supported (F = 4.81; df = 8,136; P less than .001). Concern about not having a translator in health care facilities ranked first in distinguishing the groups (F = 17.09; df = 2.71; P less than .001), followed by primary provider (F = 5.68; df = 2.71; P less than .01), feeling understood by the provider (F = 5.15; df = 2.71; P less than .01), and being able to understand written and verbal instructions given by the provider (F = 4.25; df = 2.71; P less than .05). The time-of-arrival groups also differed significantly on supplemental analyses. Subjects expressed willingness to seek more frequent health care if translators were available in health care facilities (F = 18.22; df = 2.72; P less than .001) and to change health care sites to gain a translator (F = 13.74; df = 2.72; P less than .001). PMID- 1506564 TI - Psychiatrically hospitalized college students: a pilot study. AB - This pilot study presents data on an underreported group: college students who require psychiatric hospitalization. Although the study is too small to sustain broad generalizations, the authors found indications of significant correlations between students' hospitalization and the academic cycle, substance abuse, and distance from home. It is hoped that other institutions will undertake similar studies of this group of students to provide a broader body of data from which to draw inferences regarding prevention, intervention, and psychiatric hospitalization. PMID- 1506565 TI - Screening for Chlamydia trachomatis in college women on routine gynecological exams. AB - Chlamydia trachomatis infection poses a serious threat to sexually active college women. Past research has demonstrated the difficulty of predicting infection on the basis of symptoms or physical exam. Recent studies highlight the prevalence of asymptomatic chlamydia infections. This study presents the results of screening 2,303 women for chlamydia infection on routine annual gynecological examinations at a college health center during a 22-month period. A prevalence of 6% was found. The study also assessed the differences between the 140 women identified as chlamydia positive and a control sample of 140 women who were chlamydia negative. The authors compared groups for signs and symptoms that might predict infection, but found no useful predictors. In fact, 79% of the patients who tested positive had no symptoms, and 58% of these had no signs, symptoms, or concurrent infections. Routine screening of women on annual gynecological exam is necessary to bring the chlamydia epidemic under control, the authors conclude. PMID- 1506566 TI - Sexual behavior patterns of gay university men: implications for preventing HIV infection. AB - Gay male university students less than 25 years old were studied to determine whether they had changed their sexual activity patterns to reduce the risk of HIV infection. Most had not established sexual behavior patterns typical of the older gay men who had been studied in earlier research. Although most of the participants surveyed were concerned about HIV infection, some did engage in risky sexual behavior. The risk-reduction strategies most often used were having fewer sexual partners and being more selective in choosing partners. Future HIV prevention interventions must be designed to address the needs of this generation of gay men. PMID- 1506567 TI - Student mental health needs: survey results and implications for service. AB - In preparation for planning counseling and mental health services at Columbia University, the authors conducted a mental health needs assessment survey that sampled representative numbers of students. Respondents were most concerned about academic and school-related issues, followed by concerns in the area of love relationships. Multiple regression analysis revealed certain subgroups that were more likely to have these concerns and certain health and mental health problems that were significantly associated with these concerns. The study identified serious psychological problems, including suicidal/homicidal thoughts and sexual abuse, and surveyed respondents' treatment preferences. Finally, the authors discuss how the study findings contributed to sharpening and expanding focus on different aspects of program development in the collaboration between mental health and health education. PMID- 1506568 TI - The status of nutrition education in ACHA college and university health centers. AB - An assessment of the prevalence and scope of nutrition services offered through 208 randomly selected American College Health Association member student health centers revealed that 79% of the 160 respondents provided some type of nutrition education for students. One-to-one counseling, available at 96% of the institutions, was the most common approach. The larger the school's enrollment, the more likely it was to provide programs in nutrition. All of the institutions with student populations of more than 35,000 offered some type of nutrition service, as did 52% of the 19 schools with enrollments between 2,000 and 5,000. Health educators, nurses, doctors, dietitians, and trained peer educators provided the services, with registered dietitians the most common providers and often coordinators of the programs. Costs to students for nutrition interventions were nominal; weight-management programs were the most expensive and showed the greatest variation in content. PMID- 1506569 TI - College health must advocate high quality care for students. PMID- 1506570 TI - Infection control recommendations for the dental office and the dental laboratory. PMID- 1506571 TI - Street stories. PMID- 1506572 TI - Denturist barred from practicing dentistry without a license. PMID- 1506573 TI - Patient gets new trial on negligent informed consent. PMID- 1506574 TI - Handpieces. PMID- 1506575 TI - An unfavorable light. PMID- 1506576 TI - Public perception. PMID- 1506577 TI - Tip of the iceberg. PMID- 1506579 TI - Misleading facts. PMID- 1506580 TI - Pros and cons. PMID- 1506578 TI - Sterilizing handpieces. PMID- 1506581 TI - OSHA regulations. PMID- 1506582 TI - Dentist employer vs. associate. PMID- 1506583 TI - Dental care for the elderly. PMID- 1506584 TI - Sealants. PMID- 1506585 TI - Fear of AIDS. PMID- 1506586 TI - Government and dentistry. A relationship explored. PMID- 1506588 TI - Legally speaking: when dentistry and government clash in court. AB - This article focuses on ADA advocacy in the courts. As these cases illustrate, organized dentistry's relationship can be adversial when cooperation fails. But that doesn't mean there is no room for agreement. PMID- 1506587 TI - Are we making any progress? AB - This report offers a limited view, by example, of dentistry's multifaceted interactions with several agencies on selected issues. It is intended to be neither comprehensive nor predictive. PMID- 1506589 TI - Analyzing dental procedures performed by an HIV-positive dental student. AB - No evidence of HIV transmission was found between an HIV-positive dental student and 163 treated patients. PMID- 1506590 TI - Reattaching fractured tooth segments: an esthetic alternative. AB - Reattaching fractured tooth segments offers an esthetic transitional restorative alternative to bonded composite and full crowns. The authors review this technique and demonstrate its application. PMID- 1506591 TI - Suture removal-induced bacteremia: a possible endocarditis risk. AB - Multiple intraoral suture removal isn't always a benign procedure for cardiac patients at high risk from bacteremia. Under certain conditions, antibiotic prophylaxis is recommended. PMID- 1506592 TI - Curbing the AIDS hysteria: a shared responsibility. PMID- 1506593 TI - Third molars and incisor crowding: when removal is unwarranted. AB - Recent evidence indicates that extracting unerupted mandibular third molars neither decreases interdental force measurably nor prevents mandibular incisor crowding. There are valid reasons for extracting third molars. But extraction for the exclusive purpose of relieving interdental pressure and thereby preventing incisor crowding is unwarranted. PMID- 1506594 TI - The next revolution: it's here. PMID- 1506595 TI - New patient exam and consultation: providing the initial contact. PMID- 1506596 TI - How does family status affect staff's view of employee benefits? PMID- 1506597 TI - Quality of care: update on ADA policies. ADA Office of Quality Assurance. PMID- 1506598 TI - Recollections of pioneers in nutrition: landmarks in the development of parenteral nutrition. AB - Total parenteral nutrition (TPN) has been available for only 30 years. The successful development of this therapy, in a modern sense, was initiated in the late 30s. However, history in this field goes back more than 350 years, with the first landmark being the description of general blood circulation by William Harvey in 1628. His discovery is the anatomical basis for intravenous infusions. Many investigations were performed during the following centuries showing that solutions containing electrolytes and glucose could be given intravenously in man. The accumulated knowledge of protein metabolism formed the basis for studies on intravenous nutrition with protein hydrolysates, peptides and amino acids. The observation in the late 30s by Robert Elman that amino acids in the form of protein hydrolysate could be administered safely in man was the first major step toward TPN. During the following years, major efforts were made to find methods to prepare infusion solutions with a high energy content and low osmotic pressure. The most realistic alternative seemed to be fat in the form of an emulsion. Many studies of a large number of various fat emulsions were made from the 20s until the end of the 50s. However, all of these emulsions caused severe adverse reactions in man. The first safe fat emulsion, Intralipid, was made available in the early 60s. This was the second major step toward TPN. It was then no problem to include vitamins, electrolytes and trace elements in the fat emulsions and the solutions of amino acids and glucose.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1506600 TI - Nutritional modulators of lipoprotein metabolism in patients with risk factors for coronary heart disease: diet and moderate exercise trial. AB - To study the role of diet as a risk factor for coronary heart disease (CHD), 463 adults (25-65 years, 419 males) at risk of or with CHD were assigned to group A (n = 231) receiving a cardiovasoprotective diet or group B (n = 232) receiving a normal diet in a randomized, single-blind fashion. Age, sex, risk factors and incidence of CHD were comparable between the two groups. Group A received a significantly higher percentage of calories in relation to complex carbohydrates, vegetable proteins, polyunsaturated fatty acids, and had a higher polyunsaturated:saturated fatty acid (P:S) ratio compared to control group B, which received more saturated fat and cholesterol. Group A also received more soluble dietary fiber and magnesium (Mg) and was physically more active than group B. Exercise and dietary adherence were tested by a questionnaire. After 12 weeks, results indicated a significant decrease in mean serum total cholesterol (9.0 vs 3.1%), low-density-lipoprotein cholesterol (LDL-C) (9.8 vs 3.8%) and triglyceride (11.1 vs 5.4%), and an increase in serum Mg (8.5%) in the intervention group compared to initial levels. No significant changes in mean levels were noted in the control group. Body weight significantly decreased and physical activity was significantly higher in the intervention group compared to the control group during the 12-week followup on similar intakes of energy. There were insignificant changes in high-density-lipoprotein cholesterol (HDL-C) in both groups.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1506599 TI - Dietary palmitic and oleic acids exert similar effects on serum cholesterol and lipoprotein profiles in normocholesterolemic men and women. AB - To compare the effects of dietary palmitic acid (16:0) vs oleic acid (18:1) on serum lipids, lipoproteins, and plasma eicosanoids, 33 normocholesterolemic subjects (20 males, 13 females; ages 22-41 years) were challenged with a coconut oil-rich diet for 4 weeks. Subsequently they were assigned to either a palm olein rich or olive oil-rich diet followed by a dietary crossover during two consecutive 6-week periods. Each test oil served as the sole cooking oil and contributed 23% of dietary energy or two-thirds of the total daily fat intake. Dietary myristic acid (14:0) and lauric acid (12:0) from coconut oil significantly raised all the serum lipid and lipoprotein parameters measured. Subsequent one-to-one exchange of 7% energy between 16:0 (palm olein diet) and 18:1 (olive oil diet) resulted in identical serum total cholesterol (192, 193 mg/dl), low-density lipoprotein cholesterol (LDL-C) (130, 131 mg/dl), high density lipoprotein cholesterol (HDL-C) (41, 42 mg/dl), and triglyceride (TG) (108, 106 mg/dl) concentrations. Effects attributed to gender included higher HDL in females and higher TG in males associated with the tendency for higher LDL and LDL/HDL ratios in men. However, both sexes were equally responsive to changes in dietary fat saturation. The results indicate that in healthy, normocholesterolemic humans, dietary 16:0 can be exchanged for 18:1 within the range of these fatty acids normally present in typical diets without affecting the serum lipoprotein cholesterol concentration or distribution. In addition, replacement of 12:0 + 14:0 by 16:0 + 18:1, but especially 16:0 or some component of palm olein, appeared to have a beneficial impact on an important index of thrombogenesis, i.e., the thromboxane/prostacyclin ratio in plasma. PMID- 1506601 TI - Copper deficiency in rats: the effect of clofibrate. AB - This study was undertaken to determine whether hepatic lipogenesis plays a role in the exacerbation of copper (Cu) deficiency. Forty-eight male rats were fed from weaning a Cu-deficient or adequate diet containing 62% carbohydrate as either starch or fructose with or without clofibrate for 5 weeks. Clofibrate was fed since it had been shown to possess hypolipidemic properties. Administration of clofibrate reduced the activity of the lipogenic enzyme glucose-6-phosphate dehydrogenase. Total hepatic lipid, however, was not reduced. Clofibrate did not affect hepatic lipid concentration and the pathology associated with Cu deficiency when fructose was fed was not prevented by the consumption of clofibrate. PMID- 1506602 TI - Electrophysiologic effects of magnesium sulfate infusion in patients with cardiac conduction defects. AB - We report the electrocardiographic and electrophysiologic effects of magnesium (Mg) sulfate infusion in 25 normomagnesemic patients (16 men and 9 women, aged 22 74 years; mean +/- SD, 60.4 +/- 11.9) with different cardiac conduction impairments. Ten patients had chronic ischemic heart disease, two had idiopathic dilated cardiomyopathy, two had hypertensive heart disease, three had valvular heart disease, five had sclerodegenerative heart disease and three had no clinical evidence of cardiac disease. Five patients had trifascicular block [first degree atrioventricular (A-V) block+right bundle branch block (RBBB)+left anterior hemiblock (LAH)], eight had bifascicular block (6 RBBB+LAH, 2 first degree A-V block+RBBB), four had isolated first degree A-V block and eight had bundle branch block [5 RBBB, 3 left bundle branch block (LBBB)]. Before and during Mg infusion (50 mg/min/60 min) we evaluated the A-V (P-R), intraatrial (P A), suprahisian (A-H), infrahisian (H-V) conduction times, electrical ventricular systole (Q-T), Q-T index (Q-Tc) intraventricular conduction time (QRS) and heart rate. At the end of infusion the P-R, P-A, A-H, H-V increased from 215.4 +/- 36.6, 33.6 +/- 9.1, 112.8 +/- 37.3, 69.0 +/- 12.8 ms to 217.6 +/- 37.1 (p less than 0.002), 33.8 +/- 9.4 (NS), 114.2 +/- 38.1 (p less than 0.005), 69.6 +/- 13.3 (NS) ms. QRS complex did not change (125 +/- 16.9 ms).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1506603 TI - Hypothesis: possible role of magnesium and calcium in the development of structure and function of the plasma membrane in mammalian cells and in human diseases. PMID- 1506604 TI - Plasma and erythrocyte magnesium changes following a glucose challenge during pregnancy. AB - This study examined the effects of pregnancy and glucose loading on plasma and erythrocyte (RBC) magnesium (Mg) concentrations. In a completely randomized design with repeated measures, 15 nonpregnant, 15 early pregnant (13-17 weeks) and 15 late pregnant (28-34 weeks) women ingested 100 g glucose. Blood was collected at 0, 30, 60, 120 and 180 minutes to evaluate changes in Mg levels. Fasting plasma Mg concentrations decreased slightly but not significantly as gestational age of the groups increased. Fasting RBC Mg concentrations were significantly higher (p less than 0.05) in late pregnant women compared with early pregnant and nonpregnant women. Plasma Mg responses to a glucose challenge in nonpregnant women exhibited a curvilinear pattern whereas responses in pregnant women appeared unaffected by the glucose challenge. RBC Mg concentrations for nonpregnant and early pregnant women failed to respond to the glucose challenge whereas it decreased in a linear pattern during late pregnancy. The diabetogenic effect of late pregnancy appears to affect RBC Mg. This redistribution of Mg during late pregnancy could suggest a possible role for RBC as a Mg pool. PMID- 1506605 TI - Institutionalized elderly women have lower food intake than do those living more independently (Dutch Nutrition Surveillance System). AB - The habitual intake of energy and nutrients (assessed through dietary history) among elderly women (aged 65 and over) living in a nursing home (n = 54), elderly women living in service flats and receiving their dinners from the nursing home kitchen (n = 29), and elderly women living independently (n = 52) was evaluated within the framework of the Dutch Nutrition Surveillance System. Intake of energy and nutrients was lowest among women in the nursing home and highest among those living independently. Almost all differences in absolute intake found were significant, both unadjusted and adjusted for age. In the nursing home the intake of energy and nutrients was lower at higher age. In qualitative terms the differences among the groups of women were less striking. Mean daily intakes of iron, vitamin A, thiamin, vitamin B6 and vitamin C were below the Dutch recommended dietary allowances (RDAs) among the nursing home women. Several interrelationships among nutrient intakes were found, low intake levels clustering somewhat among elderly subjects. Our data indicate that these nutritional risks are due to a lower food intake resulting in a lower intake of energy and nutrients, and owing to differences in food choice resulting in a lower nutrient density. We conclude that it is difficult to design a diet containing all essential nutrients at the RDA level in a nursing home with residents who have a relatively low intake of energy, especially among those at higher age. PMID- 1506606 TI - Vitamin E status of US children. AB - Data from several national surveys consistently show that American children have lower than recommended intakes of vitamin E, which is reflected in lower than average serum levels. Reduction in dietary fat can further exacerbate the low vitamin E status of children. The consequences of low vitamin E intake may include impaired immune responses, as seen in a study of over 500 Canadian children. Low vitamin E status has been correlated with increased risk of atherosclerosis and cardiovascular disease, cancer, cataract and impaired immune responses in adult populations. Since early signs of chronic degenerative diseases of aging have been seen in autopsies of children, efforts should be made to ensure that prolonged low intakes of vitamin E are avoided in children as well as adults. PMID- 1506607 TI - A review of cancer cachexia and abnormal glucose metabolism in humans with cancer. AB - In 1919, glucose intolerance became the earliest recognized metabolic abnormality in cancer patients. Prior to the development of severe malnutrition, colon, gastric, sarcoma, endometrial, prostate, localized head, neck, and lung cancer patients had many of the metabolic abnormalities of type II (noninsulin dependent) diabetes mellitus. These metabolic abnormalities include glucose intolerance, an increase in both hepatic glucose production (HGP) and glucose recycling, and insulin resistance. In a study of over 600 cancer patients, a diabetic pattern of glucose tolerance test was noted in over one-third of the patients. An increased rate of HGP, commonly seen in diabetics, has been noted in almost all types of cancer patients studied to date. Etiology of the increased glucose production in the cancer patient is not known, but abnormalities in the counter regulatory hormones, especially growth hormone, may contribute to the development of abnormal glucose metabolism. A second possible stimulus for the increase in HGP could be the glucose needs of the tumor. Abnormally high glucose utilization rates in small amounts of tumor tissue have recently been described. This suggests that small tumors may have large needs for glucose calories. An increase in anaerobic glycolysis in the tumor tissue can increase lactate production in the tumor-bearing human, thus supplying substrate to the liver to increase glucose production rates. In this paper, the nature of abnormal glucose metabolism in cancer patients is described. PMID- 1506609 TI - Presbyopia. PMID- 1506608 TI - Morbid obesity: selection of patients for surgery. AB - Massive obesity is associated with serious co-morbidities. After failure of extensive conservative measures, surgical procedures have developed as the only successful method for sustained weight loss. Criteria for operation are: presence of serious diseases associated with morbid obesity; greater than 45 kg above ideal weight or body mass index greater than 40 kg/m2 for usually greater than 5 years; failure of sustained weight loss on extensive conservative regimens; commitment to lifelong follow-up; and acceptable operative risk. Angina pectoris itself is not a contraindication to these operations. Patients who do not quite meet the weight criteria may still be candidates for an obesity operation in certain instances, e.g., debilitating musculoskeletal pains in weight-bearing joints, diabetes, significant hypertension, reflux esophagitis, urinary stress incontinence. Although current operations result in lasting weight loss of greater than 50% of excess weight in the majority of patients, the surgical candidate must understand and accept the principles of the procedures, the potential for serious complications, the dietary necessities, and occasional failures. PMID- 1506610 TI - Sports vision and the high school student athlete. AB - Thorough sports vision evaluations (SVE) utilizing a 30-test battery of established sports vision tests, variations of commonly accepted procedures, and newly designed instruments and/or methods were performed by the Wisconsin Sports Vision Project (WSVP) staff on 232 teenage male and female high school student athletes. Tests are described and results reveal that a state tournament qualifying girls volleyball team (n = 8) demonstrated significantly better visual skills and abilities than 1) the male and female general high school athlete sample (n = 224), 2) the female athlete sample (n = 78), and 3) the other female volleyball players in the sample (n = 46) in some areas of dominant eye vision contrast sensitivity, distance judgement, dynamic visual acuity, tachistoscopic skills, low light and glare-affected vision. PMID- 1506611 TI - Dichromacy and its effect on a young male. AB - Deuteranopia is a dichromatic color vision defect which may cause problems for an individual asked to perform color-oriented tasks. This can especially create problems for grade school children in classrooms whose instructional material depends heavily on color. This case report presents a child with a deuteranopic color vision defect who was mistakenly labeled learning disabled because of his inability to learn and perform color oriented tasks. PMID- 1506612 TI - Inferior punctal occlusion with removable silicone punctal plugs in the treatment of dry-eye related contact lens discomfort. AB - Thirty subjects complaining of a decrease in soft contact lens wearing time secondary to dry eye discomfort were selected for our study. All subjects were between the ages of 25 and 40 and selected on the basis of subjective dry eye complaints alone. Five of these subjects had punctum that were too small to facilitate plug placement and were therefore eliminated from further study. Removable silicone punctal plugs were monocularly placed in the lower puncta of the remaining 25 subjects. In an attempt to minimize the placebo effect, both puncta were manipulated equally prior to plug insertion and the patient was not told which eye had been treated. Three weeks following plug placement, blind data assessment showed that 18 of the 25 subjects reported, on average, a 34.6 percent increase in comfortable contact lens wearing time in the treated eye. Three subjects reported no subjective increase in comfortable wearing time and four subjects were unable to tolerate the punctal plugs for more than a week due to plug-related discomfort. Problematic epiphora was not reported in any of the treated eyes. Reversible inferior punctal occlusion, when tolerated, can significantly increase comfortable contact lens wearing time while still allowing enough drainage from the upper puncta to prevent epiphora. PMID- 1506613 TI - Pigment dispersion syndrome and pigmentary glaucoma. AB - The pigment dispersion syndrome is a relatively uncommon condition, occurring as a result of pigment loss from the posterior-pigmented epithelium of the iris, with subsequent redeposition of the pigment throughout the anterior chamber. Obstruction of the trabecular meshwork occasionally leads to pigmentary glaucoma, with increased intraocular pressure, optic nerve head changes, and visual field loss. We present two cases of pigmentary dispersion syndrome, one of which progressed to pigmentary glaucoma with the eventual need for laser trabeculoplasty. PMID- 1506614 TI - The True Daylight Illuminator (TDI): a less expensive source of illumination for color vision screening. AB - This experiment was designed to examine the feasibility of using the True Daylight Illuminator (TDI) as an illumination option for conducting color vision screening with the Ishihara Test(s). The MacBeth Easel Lamp was designed to provide proper illumination for performing color vision screening with a variety of pseudoisochromatic (PIC) plate tests including the Ishihara. However, over the years, the MacBeth Lamp has become so expensive that many smaller programs cannot afford to purchase one. This problem has promoted the use of alternate light sources that have had a deleterious effect on test results and in some instances contributed to job discrimination. Recently the MacBeth Division of the Kollmorgan Corporation discontinued the manufacture of the MacBeth Lamp due to lack of demand. Thus, it is important to find an inexpensive illumination option for conducting color vision screening. Two groups of subjects were used to compare test results for the 24-plate edition of the Ishihara Test using both the MacBeth Lamp and the True Daylight Illuminator. The first group contained 45 subjects with inherited color defective vision. The second group was made up of 30 color normals. The Nagel anomaloscope was used to confirm the color vision status of the subjects in both groups. Statistics to test the significance of differences between group means clearly demonstrated that there were no significant differences between the mean error scores of the two groups for these two pieces of equipment. Thus, it was concluded that the TDI can be used in lieu of the MacBeth Easel Lamp for screening color vision with the Ishihara test. PMID- 1506615 TI - Retinopathy of prematurity--review of the pathophysiology and classification. AB - This paper provides an update on current concepts concerning retinopathy of prematurity (ROP). It considers the history, risk factors and pathophysiology of ROP as well as clinical recognition of the condition. The paper also describes the approved method of classification of the disease and presents treatment options. PMID- 1506616 TI - A 1988 survey of federal service optometrists. AB - A mailed questionnaire was used to survey federal service optometrists in the U.S. Air Force, U.S. Army, U.S. Navy, U.S. Public Health Service, and the Department of Veterans Affairs. The purpose of this survey was to determine the scope of practice and level of job satisfaction of these optometrists. The results of the study were compared with those of a similar survey conducted 5 years earlier. PMID- 1506617 TI - Conservative and surgical management of incidentally discovered adrenal tumors (incidentalomas). AB - Of 50 patients with incidentalomas (INC), 18 were adrenalectomized and in 18 patients the INC was left in place. For 14 patients clinical data were insufficient for evaluation. Follow-up investigation of the 18 unoperated subjects 11-101 months (median 32.2) after the diagnosis had been made revealed unchanged size of the INC [initially 2.1 +/- 0.8 cm (mean +/- SD) at follow-up 2.0 +/- 1.0 cm]. Cushing's syndrome developed in one patient, which was not evident at the initial discovery of the INC 32 months before. "Pre-Cushing's Syndrome" was detected in 1 patient and confirmed in a second who had displayed a pathologically high dose dexamethasone suppression test 101 months before. In addition, 3 male patients with a hitherto unknown mild subclinical defect of 21 hydroxylase activity were identified. The remaining 12 patients had normal endocrine activity of their adrenals. Eighteen patients were adrenalectomized with an average tumor size of 3.96 +/- 1.88 cm. Histologically, 10 (52%) adenomas were observed, including 3 with signs of hypercortisolism. Adrenal hyperplasias were observed in 2 patients, metastasis in 1 patient. 31.5% of the INC which were removed were nonmalignant tumors of other than adrenal origin. We conclude that initially endocrinologically inactive adrenal tumors can eventually develop autonomous endocrine activity and therefore need to be reexamined at regular intervals. Conservative management with regular follow-up investigations is the preferable treatment for small incidentalomas when endocrine over-activity has been excluded and no indications of malignancy exist. Based on these observations and the literature a diagnostic and therapeutic strategy is presented. PMID- 1506618 TI - Weight reduction lowers blood pressure independently of salt restriction. AB - The existence of a link between obesity and hypertension is nowadays universally accepted; however, there are still some doubts about the fact that weight reduction induces a significant long-term decrease in blood pressure. This clinical trial aimed at evaluating the effects of marked weight loss (at least 30% of excess body weight) induced by a low-energy (600 Kcal), normal sodium diet in severely obese patients, on blood pressure at rest and during sympathetic stimulation. Eight of the 20 patients initially recruited for the study were able to reach the therapeutical goal and brought their body weight from 107 +/- 6 to 91 +/- 4 kg. Their blood pressure (BP) at rest was at the same time reduced from 137/81 +/- 5/4 to 122/74 +/- 4/4 mmHg. Also, blood pressure measured during three different stimuli (cold pressor test, handgrip and mental arithmetic test) was lowered by this nonpharmacological means. These effects are related solely to weight reduction, since no change in salt intake occurred, as demonstrated by measurements of the 24-h sodium excretion test (191 +/- 13 vs 185 +/- 10 mEq/24 h). In conclusion, these results support the hypothesis that a drastic weight loss, independently of salt restriction, significantly reduces BP at rest and during stimulation of the adrenergic nervous system. PMID- 1506619 TI - Direct effects of protirelin (TRH) on cultured porcine thyrocytes. AB - In several cases of thyroid adenoma in which no TSH was detectable in the serum, a paradoxical decrease of PB123I and its conversion rate Q (PB123I/serum total radioactivity) was observed after infusion of protirelin (TRH). The possibile direct effect of TRH on thyrocytes was therefore studied in vitro. Porcine thyroid cells were cultured in NCTC-135 medium supplemented with a serum substitute and insulin. TRH and some of its analogs enhanced the incorporation of [3H]thymidine into DNA and the uptake of radioiodide into thyrocytes. In the presence of TSH, TRH did not stimulate radioiodine uptake, whereas incorporation of [3H]thymidine into DNA was not antagonized by TSH. Thus, in this culture system, TRH had a direct effect on both growth and metabolism of thyrocytes. TSH can modulate these effects. PMID- 1506621 TI - A case of rheumatoid arthritis associated with silent thyroiditis. AB - A 41-year-old female with rheumatoid arthritis had nontender enlarged thyroid gland. Thyroid function tests revealed increased concentrations of serum free T3 (FT3, 10.8 pmol/L) and free T4 (FT4, 31.1 pmol/L) with suppressed concentration of thyrotropin (TSH, lower than 0.1 mU/L) and low 24-hour thyroidal radioactive iodine uptake (1.6%). Serum thyrotropin receptor antibody (TRAb) was negative (0%) and she had positive anti-thyroglobulin and anti-microsomal antibodies. A diagnosis of silent thyroiditis was made based on laboratory findings. Serum concentrations of FT3 and FT4 normalized one month later without treatment. The causal relationship between the two diseases is discussed. PMID- 1506620 TI - Percutaneous intranodular ethanol injection: a new treatment for autonomous thyroid adenoma. AB - Established methods for definitive ablation of autonomous thyroid nodules are surgery and radioiodine. Since it has been demonstrated that percutaneous ethanol injection can inactivate parathyroid adenomas and small hepatocellular carcinomas, we started a trial of this treatment in patients with autonomous thyroid nodules. Twenty-eight patients, 22 toxic and 6 nontoxic, all with undetectable thyrotropin serum levels and suppressed extranodular tissue on scintigraphy, were treated. Treatment consisted of percutaneous intranodular ethanol injection under ultrasound guidance. The total amount of alcohol injected ranged from 0.4 to 2.2 times the estimated nodule volume, divided into 4 to 9 injections performed at 2 to 7 day intervals. Most patients were treated with a single cycle of injections, but 7 of them required 2 cycles. The signs and symptoms of hyperthyroidism disappeared in all cases. Apparently complete cure (normal serum free thyroid hormones, thyrotropin in basal conditions and after thyrotropin releasing hormone, reactivation of extranodular tissue on scintigraphy with nodule no longer visible) was obtained in 17 patients (13 after 1 cycle and 4 after 2 cycles). Partial cure (normal serum free thyroid hormone levels, detectable thyrotropin levels with normal or blunted response to thyrotropin releasing hormone and partial reactivation of extranodular tissue on scintigraphy with nodule or parts of it still visible) was obtained in 10 patients (8 after 1 cycle and 2 after 2 cycles). In 1 patient with a very large nodule thyrotropin levels remained undetectable, but thyroid hormone levels eventually became normal. No recurrences were observed after a follow-up of 12 to 32 months (mean 20 months). No serious side effects were encountered. A clinically valuable result was obtained in all patients. These data suggest that this form of treatment could constitute an alternative to surgery and radioiodine for the ablation of autonomous thyroid nodules. PMID- 1506622 TI - A marked molecular heterogeneity of growth hormone (GH) detected in the plasma but not pituitary of a patient with acromegaly: comparison with other acromegalics and an implication for discrepant plasma levels of GH and insulin like growth factor. AB - We experienced a 41-year-old acromegalic male (Case 1) in whom the basal plasma GH was extremely high (320-450 ng/mL) but plasma IGF-I was only slightly elevated (2.0-2.8 U/mL). His nutritional condition and associated diabetes mellitus did not appear to be responsible for the relatively low IGF-I level, and a GH autoantibody in the plasma was absent. We thus performed gel filtration analyses of his plasma and somatotroph adenoma to determine elution patterns of immunoreactive (IR) and receptor active (RA) GH. For comparison, the same studies were carried out on plasmas and somatotroph adenomas obtained from three other acromegalics (Cases 2-4) whose basal plasma GH and IGF-I levels were 22-45 ng/mL and 3.5-6.0 U/mL, respectively. IR GH in Case 1's plasma distributed over an extremely wide range keeping similar titers rather than showing three discernible components (big-big, big, and little GH) as did plasmas and adenomas from Cases 2 4. And, most of the IR GH in Case 1's plasma was eluted in such fractions that contained low levels of RA GH, indicating a minor proportion of biologically active GH. However, interestingly, the chromatographic profile and total GH content of Case 1's adenoma were similar to those of Cases 2-4's adenomas. These results may, at least in part, explain the discrepancy between the plasma GH and IGF-I levels of Case 1. The unexpectedly different GH elution patterns between the plasma and adenoma from this patient, may suggest a contribution of certain plasma factor(s) to the unusual chromatographic profile of plasma GH. PMID- 1506623 TI - Effect of progesterone supplementation in repeat-breeder cattle on conception and plasma progesterone. AB - Reposital-type progesterone (75 mg/d for cows, 40 mg/d for heifers) or saline were administered to 24 Holstein cattle to assess the effects of exogenous progesterone (P) on fertility in repeat-breeders. Treatments were administered daily from day 6 to 10 after fourth, fifth and sixth insemination. Cumulative conception rate (57.1%) for the fourth through sixth insemination was affected by lactation number, service number, plasma P (4.67 ng/ml for pregnant cows vs 4.06 ng/ml for nonpregnant cows) and corpus luteum size on days 5 and 15. Plasma P concentrations were affected by day of cycle and size of corpus luteum on both ovaries on day 15. A treatment by day interaction accounted for higher plasma P in P-treated cattle than saline-treated cattle from day 5 through 15. Administration of exogenous P during early life of the corpus luteum in the repeat-breeder increased plasma P. Higher plasma P was associated with insemination success. PMID- 1506624 TI - Eurohep. A European Community sponsored concerted action on viral hepatitis: its rationale and execution. PMID- 1506625 TI - Quantitative studies on fatty acid metabolism in isolated parenchymal cells from normal and cirrhotic livers in rats. AB - Parenchymal cells isolated from normal and thioacetamide-induced micronodular cirrhotic rat livers were used to evaluate changes in hepatocellular fatty acid (FA) metabolism in cirrhosis. Exogenous free FA (FFA) are rapidly taken up by hepatocytes obtained either from normal or cirrhotic livers. They are predominantly esterified to triglycerides and accumulate intracytoplasmatically as lipid droplets with increasing cellular FFA uptake. In the parenchymal cells of cirrhotic livers, however, the following changes were observed when compared with controls: (i) decreased cellular output of esterified FA derived both from exogenous sources and from de novo FA synthesis; (ii) increased total ketone body production, mainly as beta-hydroxybutyrate; (iii) decreased cholesterol synthesis; and (iv) enhanced incorporation of newly synthesized FA into phospholipids in spite of an unaffected rate of FA synthesis. In summary, the data provide evidence for intrinsic alterations in the lipid metabolism in the parenchymal cells of cirrhotic livers which are preserved in the isolated hepatocytes under optimum incubation conditions for oxygen and substrate supply. PMID- 1506626 TI - Comparative effects of epidermal growth factor, an insulin-glucagon combination, and a hepatocyte growth factor preparation on epidermal growth factor receptors. AB - We investigated the changes in cell surface epidermal growth factor (EGF) receptors in the liver after partial hepatectomy, and in primary adult rat hepatocyte cultures following stimulation with either EGF, or a preparation of hepatocyte growth factor, or an insulin-glucagon combination. We confirmed a reduction in EGF receptors on hepatocytes after partial hepatectomy and a rapid down-regulation of EGF receptors on normal hepatocytes in vitro following exposure to EGF. Insulin and glucagon and hepatocyte growth factor, whilst initiating hepatocyte DNA synthesis, had only slight effects on their EGF binding capacity and EGF-receptor affinity. These results indicate that changes in cell membranes early in proliferation have only non-specific effects on EGF receptors, and, therefore, support the role of ligand binding to the EGF receptor as an important component of hepatocyte proliferation in vivo. PMID- 1506627 TI - Chronic alcohol intoxication decreases the serum level of hepatitis B surface antigen in transgenic mice. AB - Hepatitis B virus (HBV) infections with an unusual serological profile, viz. positivity of HBV-DNA in the absence of hepatitis B surface antigen (HBsAg), have been described in alcoholics. This atypical pattern could be due to a low circulating level of viral particles rendering HBsAg undetectable with commercial kits, whereas HBV-DNA remains positive using the highly sensitive hybridization technique. We hypothesize that the well-known alcohol-induced impairment of protein secretion could also concern HBsAg particles and leads to a decrease in serum levels of the HBs antigen. To verify this hypothesis, we used HBsAg positive transgenic mice as an animal model. Twelve HBsAg+ mice were separated into two groups; one group (n = 6) was submitted to increasing alcoholisation over an 18-week period, while the other (n = 6) was water fed. Seven HBsAg- littermates acted as controls: three received the alcohol regimen and the remaining four water. Chronic excessive alcoholisation lead to a significant decrease in serum HBsAg concentrations, while there was no obvious change in liver S mRNA. Ultrastructural studies showed a significant decrease in the number of microtubules in the livers of alcohol-fed mice. Finally, immunohistochemical studies performed at the end of the experiment showed a greater accumulation of HBsAg in the livers of HBsAg+ alcohol-fed (mainly located in the centrilobular area) than in the HBsAg+ water-fed mice. Our results (i) validate our initial hypothesis that chronic alcohol abuse leads to a decrease in serum HBsAg concentrations. This could explain, in part at least, the serological dissociations which were observed. (ii) Confirm the utility of screening serum HBV-DNA in alcoholics.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1506628 TI - Prognostic value of hemostatic parameters after liver transplantation. AB - The prognostic value of hemostatic parameters after orthotopic liver transplantation was evaluated in 37 consecutive patients. Six simple hemostatic parameters (prothrombin time, activated partial thromboplastin time, thrombin time, thrombin coagulase time, plasma fibrinogen and platelet count) were obtained for each patient pre-transplantation and daily post-transplantation for at least 8 days. Using the results of these tests, the degree of hemostatic impairment was arbitrarily scored from 0 to 6. Starting from the first day post transplantation, hemostatic parameters improved progressively, reaching plateau values on day 7 post-transplantation. On day 8 there were significant differences in the activated partial thromboplastin time, prothrombin time, and in the overall hemostatic scores between patients who survived at least 6 months and those who died. Comparing these hemostasis parameters with such liver function tests as AST, ALT and serum bilirubin, univariate analysis showed that activated partial thromboplastin time, coagulation score and AST were significant predictors of 6-month survival, but by multivariate analysis (Cox proportional hazard rate model) only the activated partial thromboplastin time was an independent predictor. Hence, a simple coagulation test is useful for predicting the survival of patients undergoing liver transplantation. PMID- 1506629 TI - T lymphocytes from patients with primary biliary cirrhosis produce reduced amounts of lymphotoxin, tumor necrosis factor and interferon-gamma upon mitogen stimulation. AB - Primary biliary cirrhosis (PBC) is considered an autoimmune disease characterized by destruction of small intrahepatic bile ducts by lymphocytes. Altered functions of these lymphocytes might reflect an abnormal immune response leading to tissue damage. We investigated lymphokine secretion by mitogen-stimulated T lymphocytes from the liver biopsies of patients with PBC and for comparison also peripheral blood. In PBC, diminished synthesis of lymphotoxin (TNF beta), tumor necrosis factor (TNF alpha) and interferon-gamma (IFN gamma) was found both in T-cell lines from liver tissue and in peripheral blood. The reduction was most prominent for TNF beta in early histological stages of PBC, and appeared to be a stable phenomenon when T cells were tested after long-term tissue culture. Analysis of mRNA levels indicates a possible link between reduced TNF beta production and a defect in interleukin-2 transcription. The data suggest that diminished lymphokine production in patients with PBC may play an important role in the immunopathogenesis of this disease. PMID- 1506630 TI - Ultrasound, hepatic lymph nodes and primary biliary cirrhosis. AB - Thirty-five consecutive patients with primary biliary cirrhosis were examined using liver biopsy, laboratory tests and ultrasonography of the hepato-duodenal ligament to investigate the possible correlation between enlarged lymph nodes in the hepato-duodenal ligament and biochemical activity, histologic activity or stage and/or humoral immunoreactivity. We found a positive correlation between the size of the largest lymph node and laboratory values of cholestasis, hepatocellular damage and increased humoral immunoreactivity. On the other hand, we found a negative association between lymph node size and hepatocellular function. When twelve of the patients were reexamined after at least 10 months, in the majority of the patients changes in lymph node size were accompanied by similar changes in markers of cholestasis, hepatocellular damage and immunoreactivity. Prognostic index was also directly associated with lymph node size in most of these patients. No association between lymph node size and histologic stage was observed. PMID- 1506631 TI - Deterioration of cholestasis after endoscopic retrograde cholangiography in advanced primary sclerosing cholangitis. AB - Complications of endoscopic retrograde cholangiography specific to patients with primary sclerosing cholangitis have not yet been reported. We observed transient rises of serum bilirubin after diagnostic endoscopic retrograde cholangiography in five of 15 patients and persistent rises in three of 15 patients with primary sclerosing cholangitis examined consecutively by endoscopic retrograde cholangiography from 1985 to 1990. Deterioration of cholestasis was particularly associated with advanced disease. Seven of eight patients with deterioration after endoscopic retrograde cholangiography had septal fibrosis (stage III) or cirrhosis (stage IV) and a priori elevated serum bilirubin levels. In contrast, all patients with no deterioration of cholestasis following endoscopic retrograde cholangiography had early histological changes (stage I-II), and all but one patient had normal serum bilirubin levels. We conclude that the potentially harmful effects on biliary excretion must be taken into account when the use of endoscopic retrograde cholangiography is being considered in patients with advanced primary sclerosing cholangitis. PMID- 1506632 TI - Fipexide-induced fulminant hepatitis. Report of three cases with emergency liver transplantation. AB - Fipexide belongs to a new class of cognition activators and is noted for its lack of amphetamin-like side effects. We describe three patients who developed fulminant hepatic failure less than 2 months after beginning fipexide administration. The mean interval from the onset of jaundice to the onset of encephalopathy was 8 days. Emergency liver transplantation was undertaken when factor V was 20% of normal or less and coma developed. All patients were transplanted less than 1 week after the onset of encephalopathy. Two survived and one died immediately after transplantation. Histologic examination of the livers revealed massive liver cell necrosis, predominantly centrilobular, and a moderate inflammatory infiltrate within the portal spaces. We conclude that fipexide can induce massive liver cell necrosis and fulminant liver failure. As a result of this life-threatening complication, reconsideration of the indications for this drug is warranted. PMID- 1506633 TI - Lactoferrin and lysozyme in the intrahepatic bile duct of normal livers and hepatolithiasis. An immunohistochemical study. AB - Lactoferrin and lysozyme have bactericidal activities and are responsible for mucosal defense against local bacterial infections. To assess the local defense mechanisms in the intrahepatic biliary tree, we studied the distribution of lactoferrin and lysozyme immunohistochemically in 14 normal autopsy livers and in 29 surgically resected and two autopsy livers of hepatolithiasis. In the latter, bacterial infection was constantly found. Lactoferrin and lysozyme were detected in low doses and in specific areas in the intramural and extramural glands of certain normal livers. In contrast, in hepatolithiasis, the incidence of lactoferrin- and lysozyme-positive cases significantly increased both in the intramural glands (94% and 77% of 31 cases, respectively) and in the extramural glands (72% and 48% of 29 cases, respectively) (p less than 0.01) in the stone containing bile ducts. These glands proliferated considerably in the stone containing bile ducts and were stained more widely and intensely than in normal livers. These data suggest that these proliferated peribiliary glands in the stone-containing bile ducts produce and secrete significant amounts of lactoferrin and lysozyme. Increased production and secretion of lactoferrin and lysozyme suggests activated local defense mechanisms against bacterial infection in the stone-containing bile ducts, and may be beneficial for inhibition of the growth of calculi and prevention of the suppurative inflammation. PMID- 1506634 TI - Liver damage from flucloxacillin, cloxacillin and dicloxacillin. AB - We describe a case of severe cholestatic liver disease, which persisted for 7 years, and was probably induced by flucloxacillin. We also report a survey of 77 liver reactions which were probably or possibly induced by penicillinase resistant penicillins and spontaneously reported to the Swedish Adverse Drug Reactions Advisory Committee. The reactions were usually cholestatic with a tendency to a protracted course. There is some evidence for an immunoallergic idiosyncratic reaction. The incidence of reported liver reactions was estimated from sales data to be 1.6-2.9 per million DDD (defined daily doses) or, for flucloxacillin 1:11,000-1:30,000 prescriptions. Female sex, age and high daily doses seemed to be associated with higher risk of liver reactions from flucloxacillin. PMID- 1506635 TI - The origins and kinetics of bilirubin in dogs with hepatobiliary and haemolytic diseases. AB - In 35 dogs with spontaneous hepatobiliary liver disease the kinetics and the sources of bilirubin were quantified. The disorders were extrahepatic bile duct obstruction (n = 4), fulminant hepatitis (n = 2), (sub)acute hepatitis (n = 5), chronic active hepatitis (CAH) with cirrhosis (n = 6), hepatic lymphosarcoma (n = 5), centrizonal necrosis secondary to haemolytic anaemia (n = 6) and other (n = 2). The plasma disappearance of [3H]bilirubin was analyzed with a two-compartment model in all dogs. The ratio early labeled/late labeled bilirubin was determined by measuring the incorporation of [14C]glycine into erythrocyte haem and faecal stercobilin. By introducing this relation in the model analysis the bilirubin production rates from erythrocyte destruction (PE), ineffective erythropoiesis (PI) and hepatic haemoprotein (PL) could be quantified. Total bilirubin turnover was increased in both primary haemolytic disease and most cases of hepatobiliary disease. Erythrocyte survival was reduced in all cases but one. The bilirubin clearance was impaired to 30-50% of the normal value in most cases of hepatobiliary disease and also in primary haemolysis. In dogs with fulminant hepatitis, and cirrhosis with or without CAH, the clearance rates were reduced to values below 15% of normal. In these dogs both an impaired clearance and an increased production were important determinants of hyperbilirubinaemia. In other cases plasma bilirubin was primarily determined by increased production. These clearances and production rates were similar in haemolysis and in many cases of primary hepatobiliary disease. The hepatic haemoprotein turnover was quite variable in all subgroups, ranging from 1-74% of the total bilirubin turnover.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1506636 TI - Relationship of portal pressure, anorectal varices and hemorrhoids in cirrhotic patients. AB - In a prospective study of 103 consecutive cirrhotic patients a high prevalence (43%) of anorectal varices was found compared with only 2% in 103 age- and sex matched control subjects (p less than 0.001). However, there was no significant difference between the prevalences of hemorrhoids in cirrhotic patients and in control subjects (79% vs. 83%, p greater than 0.05). The hepatic venous pressure gradient of cirrhotic patients with anorectal varices was similar to cirrhotic patients without anorectal varices (14 +/- 6 mmHg, n = 22, vs. 16 +/- 7 mmHg, n = 39, p greater than 0.05. There was no significant difference in the hepatic venous pressure gradient between cirrhotic patients with and without hemorrhoids (15 +/- 6 mmHg, n = 47, vs. 16 +/- 8 mmHg, n = 14, p greater than 0.05). The prevalence of anorectal varices and hemorrhoids in cirrhotic patients had no relation to Child-Pugh's grading, esophageal varices with and without sclerotherapy and ascites. We conclude that anorectal varices are common in cirrhotic patients. Anorectal varices and hemorrhoids are not related to the degree of portal pressure. PMID- 1506637 TI - Assessment of the renin-angiotensin system in cirrhotic patients. Comparison between plasma renin activity and direct measurement of immunoreactive renin. AB - The renin-angiotensin system plays an important physiological role and has prognostic significance in cirrhotics with ascites. The degree of stimulation of this system is usually estimated by measuring plasma renin activity after incubation periods of 2-3 h. Recent investigations showed that the direct measurement of immunoreactive renin also estimates the degree of activity of the system. In this study, immunoreactive renin and plasma renin activity (measured at incubation periods of 10, 20, 50 and 180 min) were determined in ten healthy subjects, five hyperreninemic non-hepatic patients and 47 cirrhotics with ascites. Cirrhotic patients showed significantly higher plasma renin activity (5.1 +/- 0.9 ng/ml per h, p less than 0.05) and immunoreactive renin (145.4 +/- 24.4 pg/ml, p less than 0.01) than healthy subjects (1.2 +/- 0.15 ng/ml per h and 25.1 +/- 1.1 pg/ml, respectively). The angiotensin I generation rate was constant during the 3-h incubation in 22 cirrhotics and a close relationship (r = 0.956, p less than 0.001) between plasma renin activity (3.5 +/- 1.6 ng/ml per h) and immunoreactive renin (71 +/- 25 pg/ml) was observed in these patients. In the remaining 25 cirrhotics the generation rate of angiotensin I declined with time and the calculated plasma renin activity at 180 min was lower than the activity calculated at 10 min by 50.7%.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1506638 TI - Who benefits from endoscopic sclerotherapy of bleeding oesophageal varices? Proposal for differential indications. The Copenhagen Esophageal Varices Sclerotherapy Project. AB - The value of early sclerotherapy for variceal haemorrhage remains unsettled, possibly because the treatment may be beneficial to some patients and harmful to others. On the basis of a randomized clinical trial of sclerotherapy in 187 patients presenting with their first variceal haemorrhage, we examined the relationship between clinical, endoscopic and biochemical characteristics at admission and the treatment effect on mortality. As previously published, sclerotherapy had no overall effect on the very high mortality during the first 6 weeks (47%), but thereafter the mortality and risk of rebleeding were reduced. The analysis showed that in the 48% of the patients with disturbed consciousness and/or elevated plasma creatinine, sclerotherapy considerably increased short term mortality, and this was not compensated for by increased long-term survival. Among patients without these characteristics, sclerotherapy reduced mortality in the 25% with ascites, but did not affect short-term mortality in the 27% without. Sclerotherapy significantly improved the long-term survival of these patients. The results suggest that sclerotherapy should not be used in patients with disturbed cerebral or renal function, whereas it may be beneficial in patients without these characteristics. PMID- 1506639 TI - Phosphorus-31 nuclear magnetic resonance of isolated rat liver during hypothermic ischemia and subsequent normothermic perfusion. AB - The effects of prolonged hypothermic ischemia and subsequent normothermic perfusion on the energetic metabolism and intracellular pH (pHin) of isolated rat livers were studied by phosphorus-31 nuclear magnetic resonance spectroscopy. Nucleoside triphosphate (NTP) depletion and intracellular pH were studied within an 18-h-storage phase, by using the following preservation media: Eurocollins (EC), UW Lactobionate (UW) and Bretschneider's solution (HTK). Values obtained after 8-h ischemia were chosen to estimate the performance of the various media: NTP levels were 37 +/- 7%, 10 +/- 5% and 0% of control levels, respectively, in livers stored in UW, HTK and EC solutions. pHin reached values of 7.15 +/- 0.10 in UW and HTK, and 6.96 +/- 0.10 in EC-stored livers. Ischemic damage was assessed by reperfusing the stored organ with Krebs medium: NTP recovery was around 70 +/- 20% for the three solutions used. Recovery of pHin was near the control value (7.23 +/- 0.08), except for EC solution (7.05 +/- 0.20). The main results are that (i) the rates of NTP and pHin decrease are strongly dependent on the nature of the preservation solution, whereas (ii) NTP recovery is not significantly different during post-ischemic reperfusion. With regard to animal survival, UW solution is at present considered largely superior to EC medium for liver preservation. Thus, our data suggest that the rates of NTP depletion and pHin fall during cold preservation could be both considered as better indicators assessing liver injury than the post-ischemic NTP recovery. PMID- 1506640 TI - The epidemiology of hepatitis delta infection in Italy. Promoting Group. AB - The epidemiology of HDV infection in Italy was assessed in a retrospective study involving 1556 HBsAg chronic carriers on their first presentation at one of the 35 Liver Units in 1987. Total anti-HD was detected in 23.4% of HBsAg carriers and was significantly more frequent in southern than in northern Italy (26.6% vs. 19.1%, p less than 0.01). Age distribution showed that 73% of the anti-HD positive subjects, but only 56% of the anti-HD-negative subjects, were under 40 years of age (p less than 0.01). Anti-HD prevalence increased with the severity of the liver disease from 3.8% in healthy carriers to 42.5% in cirrhosis. No geographical statistical difference was found among HBsAg healthy carriers or subjects with chronic persistent hepatitis (CPH), while among patients with chronic active hepatitis (CAH) or cirrhosis anti-HD prevalence was much higher in the south (p less than 0.01). The various potential risk factors were evaluated by multiple logistic regression analysis. HDV infection was independently related to young age, residence in the south, i.v. drug abuse, a large family and household contact with an anti-HD-positive carrier. No association was found with blood transfusion or male homosexuality. These findings confirm that HDV infection is endemic in Italy, particularly in some southern areas, where intrafamily contact probably at a young age may favour the spread of the infection. PMID- 1506641 TI - Syncytial giant-cell hepatitis--a specific disease entity? AB - Syncytial giant-cell hepatitis was recently reported to be related to a paramyxovirus and carried a poor prognosis. Twelve patients with syncytial giant cell hepatitis seen in an 8 1/2-year period in our institute were reviewed. Seven patients had an identifiable aetiological cause: two had autoimmune chronic active hepatitis, one had primary sclerosing cholangitis and autoimmune chronic active hepatitis, two presented with prolonged jaundice after acute hepatitis A and B, one had chronic Epstein-Barr virus infection and the remaining patient was seropositive for antibody to hepatitis C virus. One patient with autoimmune chronic active hepatitis who had frequent syncytial giant cells in the liver responded promptly to corticosteroid treatment and a repeated biopsy 3 years later showed histological improvement with a marked decrease in the number of syncytial giant cells. Of the remaining five patients, three ran a clinical course of fulminant hepatic failure and two had severe chronic active hepatitis. These data indicate that syncytial giant-cell hepatitis is unlikely to be related to only one single aetiological agent and that syncytial giant-cell hepatitis does not always carry an ominous prognosis. PMID- 1506642 TI - Functional spectrum of sinusoidal endothelial liver cells. Filtration, endocytosis, synthetic capacities and intercellular communication. PMID- 1506643 TI - The origins and kinetics of bilirubin in healthy dogs, in comparison with man. AB - The origins and the kinetics of unconjugated bilirubin were assessed in 25 healthy dogs. Bilirubin kinetics were measured by the analysis of the plasma disappearance of [3H]bilirubin in a two-compartment model. The relative bilirubin productions from erythrocyte haem degradation and early labeled bilirubin were determined by measuring the incorporation of [14C]glycine in erythrocyte haem and in fecal stercobilin. The incorporation of this relation into the model permitted the quantitation of the bilirubin production from erythrocyte destruction, ineffective erythropoiesis and the catabolism of hepatic haemoproteins. The contribution of the three bilirubin sources to the plasma concentration was derived from the calculated fraction reflux into the plasma of bilirubin produced in the liver from hepatic haemoproteins. Other calculated model-dependent and independent parameters were plasma bilirubin clearance, hepatic bilirubin extraction efficiency, pool sizes, and the fractional transfer rates which reflect the hepatic uptake process, reflux from liver to the plasma, and the conjugating enzyme activity. In plasma of healthy dogs only unconjugated bilirubin was detected. It averaged 0.68 mumol/l, which is far below levels in man. This is probably due to the 20-fold higher hepatic clearance rate in dogs (median 32.2; range 21.6-43.9 ml/kg per min). In addition, fasting hyperbilirubinaemia could not be documented in the dog. The total bilirubin turnover was 14.9 (12.6-17.1) mumol/kg (median and 95% range), with 67 (60-70)% derived from erythrocyte degradation, 5.3 (4.7-5.5)% from ineffective erythropoiesis and 27.7 (24.5-35.3)% from hepatic haemoproteins. The figures for the plasma bilirubin turnover were 12.3 (10.3-14.2) mumol/kg per day, 79 (75 84)%, 6.3 (6.0-6.6)% and 14.8 (9.2-18.9)%, respectively. The presented model permits the simultaneous quantitation of both the origins and the kinetics of bilirubin. The application of this approach in pathological conditions is expected to provide better insight in the pathophysiology of acquired hyperbilirubinaemia. PMID- 1506644 TI - Biological standards for hepatitis B virus assays. PMID- 1506646 TI - Demonstration of sensitized lymphocytes to trimethoprim/sulfamethoxazole and ofloxacin in a patient with cholestatic hepatitis. PMID- 1506645 TI - Definitions, methodology and therapeutic strategies in portal hypertension. A Consensus Development Workshop, Baveno, Lake Maggiore, Italy, April 5 and 6, 1990. PMID- 1506647 TI - Interindividual variability of the number connection test. PMID- 1506648 TI - Horizontal transmission of hepatitis B virus infection. PMID- 1506649 TI - A mechanism of accumulation and activation of polymorphonuclear cells and macrophages in the liver of alcoholics: production of chemotactic factor by hepatocytes exposed to ethanol. PMID- 1506650 TI - Effects of long-acting superoxide dismutase on postischemic liver injury in rats with cirrhosis. PMID- 1506651 TI - Enoxacin acute liver injury. PMID- 1506652 TI - Portal pressure response to propranolol in portal hypertension. PMID- 1506653 TI - Simultaneous dialytic ultrafiltration and intraperitoneal reinfusion in cirrhotic patients with intractable ascites. Preliminary results of a comparative study versus large paracentesis. PMID- 1506654 TI - Theophylline metabolism in patients with hepatosplenic mansoniasis and cirrhosis. AB - The pharmacokinetics of theophylline were studied in 12 patients with hepatosplenic mansoniasis, 14 patients with cirrhosis and 16 normal controls. Following a single intravenous dose of aminophylline volumes of distribution, serum half-lives and body clearances were determined. Volumes of distribution of theophylline in patients with schistosomiasis (mean 0.624 l/kg) did not differ from cirrhotic patients (mean 0.616 l/kg) or normal controls (mean 0.593 l/kg). Cirrhotic patients had a prolonged half-life compared to normal subjects (mean 22.1 vs. 9.9 h), while patients with schistosomiasis did not substantially differ from normal controls (15.8 vs. 9.9 h). Body clearance in patients with schistosomiasis was similar to controls (34.02 vs. 49.20 ml/h per kg) but decreased (29.24 ml/h per kg) in patients with cirrhosis. Individual analysis of the group with schistosomiasis disclosed three patients with reduced theophylline elimination. No relationship was found between laboratory tests of liver function and the pharmacokinetics of theophylline in any group. The administration of theophylline to patients with hepatosplenic schistosomiasis, although less dangerous than in cirrhosis, must be closely followed. PMID- 1506655 TI - Hepatocyte swelling and portal hypertension. PMID- 1506656 TI - Hemodynamic effects of a combination of vasopressin and ketanserin in patients with hepatitis b-related cirrhosis. AB - We measured the hemodynamic effects of intravenous vasopressin, ketanserin (a 5 hydroxytryptamine-2 receptor blocker), and vasopressin plus ketanserin in 33 patients with hepatitis B-related cirrhosis. Thirteen patients received vasopressin alone (0.66 units/min), ten patients ketanserin alone (10 mg), and ten patients vasopressin followed by vasopressin plus ketanserin. Vasopressin alone reduced the hepatic venous pressure gradient (from 18 +/- 5, mean +/- S.D., to 9 +/- 3 mmHg, p less than 0.0001) and cardiac output (p less than 0.0001), but increased mean arterial pressure (p less than 0.005), mean pulmonary arterial pressure (p less than 0.0001), pulmonary capillary wedge pressure (p less than 0.0001), and systemic vascular resistance (p less than 0.001). There was no significant change in heart rate. Ketanserin alone produced a significant fall in the hepatic venous pressure gradient (from 16 +/- 4 to 13 +/- 3 mmHg, p less than 0.0001), mean arterial pressure (p less than 0.005), mean pulmonary arterial pressure (p less than 0.005), and pulmonary capillary wedge pressure (p less than 0.005). Heart rate, cardiac output, and systemic vascular resistance were not significantly changed. The addition of ketanserin to vasopressin corrected most of the systemic hemodynamic disturbances produced by vasopressin. This combination did not lead to a further reduction in the hepatic venous pressure gradient. We conclude that intravenous ketanserin reduces portal pressure in patients with hepatitis B-related cirrhosis. The addition of ketanserin to vasopressin improves the detrimental systemic hemodynamic effects of vasopressin without further reducing the portal pressure. PMID- 1506657 TI - Molecular composition of biliary phosphatidylcholines, as related to cholesterol saturation, transport and nucleation in human gallbladder bile. AB - It has been suggested that qualitative changes in bile phosphatidylcholine (lecithin) play a role in the pathogenesis of cholesterol gallstones. We investigated the possible relationship between the molecular composition and hydrophobicity of biliary lecithins and bile cholesterol saturation, nucleation time and the mode of cholesterol transport in human gallbladder bile. Nineteen patients (12 with and seven without gallstones) undergoing abdominal surgery were studied. Bile cholesterol saturation ranged from 77% to 186% (median: 123%) and nucleation time from 1 to 24 days (median: 3 days). Biliary lipid carriers (vesicles and mixed micelles) were separated using Superose-6 gel chromatography and their lipid content was quantitated. Biliary lecithin composition was analyzed by HPLC. Fourteen individual molecular species were detected in the bile: none were related to cholesterol saturation or nucleation time. An arbitrary cumulative index of lecithin hydrophobicity was computed for each bile sample, based on the HPLC capacity factor of the individual species and their percent mole fraction: this index ranged from 47.0 and 58.5 (median: 49) and was unrelated to cholesterol saturation and nucleation time. The biliary concentration of sn-1 palmitoyl:sn-2 arachidonoyl lecithin was significantly correlated (p less than 0.01) with the fraction of cholesterol carried by mixed micelles. This finding suggests that arachidonoyl lecithin may play a modulatory role in the partitioning of cholesterol among biliary carriers. We conclude that major abnormalities in the composition of biliary lecithins are unlikely to play a causative role in the pathogenesis of cholesterol gallstone, although the role of arachidonoyl species requires further investigation. PMID- 1506658 TI - Antimitochondrial antibodies in primary biliary cirrhosis. A clue to its etiopathogenesis? PMID- 1506659 TI - Bromosulfophthalein disposition in chronically bile duct obstructed rats. AB - The disposition of bromosulfophthalein was studied in chronically bile duct obstructed rats. In this model a catheter was inserted into the common bile duct and the distal tip was sealed. Resumption of bile flow was achieved with great ease. Obstruction of bile duct for 18 days in rats resulted in elevated bilirubin, ALT, AST, and alkaline phosphatase levels. Portal hypertension developed within this period (11.6 +/- 0.5 in obstructed rats vs. 8.6 +/- 0.6 mm Hg in sham-operated group). After the bile duct obstruction was opened, the half life time for elimination of bromosulfophthalein (42.30 +/- 6.47 min) was longer than in sham-operated rats (21.23 +/- 3.34 min). Plasma clearance was reduced by 70% in bile duct obstructed rats. In spite of increased bile flow rate, biliary excretion of the dye was reduced by 40% in chronically bile duct obstructed rats. Hepatic glutathione levels were significantly reduced by 20% in this model. The specific activity of glutathione S-transferase with chlorodinitrobenzene and styrene oxide, as substrates, was reduced by 50% and 30%, respectively. However, the percent of conjugated bromosulfophthalein in bile was similar to that of sham operated rats. PMID- 1506660 TI - Effects of ursodeoxycholate, its glucuronide and disulfate and beta-muricholate on biliary bicarbonate concentration and biliary lipid excretion. AB - We previously reported that high-dose ursodeoxycholate (UDC) infusion in rats resulted in extensive glucuronidation of UDC, and speculated that the glucuronidation causes bicarbonate-rich hypercholeresis induced by UDC (Takikawa, H., Sano, N., Narita, T. and Yamanaka, M. Hepatology 1990; 11: 743-749). To test this hypothesis, UDC, UDC-3-O-glucuronide, UDC-3,7-disulfate and beta-muricholate were separately and intravenously infused into rats (1 mumol/min per 100 g), and biliary bicarbonate concentration was measured. The effects of these bile acids on biliary lipid secretion were also studied. All four bile acids increased bile flow and biliary bile acid excretion. UDC and beta-muricholate significantly increased biliary bicarbonate concentration, whereas UDC glucuronide and disulfate did not. Independence of UDC glucuronide excretion and biliary bicarbonate concentration was also confirmed in EHBR, a hyperbilirubinemic mutant Sprague-Dawley rat. In this case biliary bicarbonate concentration also increased in spite of the absence of UDC glucuronide in the bile after UDC infusion. Biliary phospholipid secretion was increased with UDC, unchanged with beta muricholate, and decreased with UDC glucuronide and disulfate. Biliary cholesterol secretion was increased with UDC, unchanged with beta-muricholate and UDC glucuronide, and decreased with UDC disulfate. These data indicate that glucuronidation is not the cause of bicarbonate-rich hypercholeresis induced by UDC but that glucuronidation and sulfation change the effect of UDC on biliary lipid secretion. PMID- 1506661 TI - The effect of alcohol-induced hepatomegaly on portal hypertension in cirrhotic rats. AB - Male Sprague-Dawley rats with CCl4-induced cirrhosis (confirmed by increased collagen content and light microscopy) were fed either ethanol (Group A, n = 9) or isocaloric carbohydrate diet (Group B, n = 8) for 4 weeks. Histologic and hemodynamic measurements were obtained in the awake state before (time 1) and after the 4 weeks of diet (time 2). Portal-systemic shunts were evaluated using radiolabelled microspheres. Liver weight was increased in Group A (16.5 +/- 0.5 vs. 14.2 +/- 0.5 g, mean +/- SE, p less than 0.005) as was the ratio of liver weight over total body weight (3.41 +/- 0.05 vs. 2.86 +/- 0.09%, p less than 0.0001, +19.2%). Hepatocytes surface area was increased in the ethanol group (357 +/- 9 vs. 294 +/- 7 microns 2, p less than 0.0001). In Group B, only 9 +/- 2% of hepatocytes had steatosis as opposed to 69 +/- 3% of centronodular and 34 +/- 3% of perinodular hepatocytes in Group A (p less than 0.001). Portal pressure remained stable in both groups (time 1 (A) 16.9 +/- 0.8, (B) 15.8 +/- 1.1 mmHg, n.s.; time 2 (A) 15.9 +/- 0.7, (B) 15.8 +/- 0.6 mmHg, n.s.). Portal-systemic shunts did not change with time or diet (time 1 (A) 10.6 +/- 3.7%, (B) 4.1 +/- 2.1%, n.s.; time 2 (A) 13.4 +/- 5.9%, (B) 10.8 +/- 4.3%, n.s.).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1506662 TI - Copper metabolism in hypercupremic human livers. Studies of its subcellular distribution, association with binding proteins and expression of mRNAs. AB - In the present study we have used differential centrifugation, size exclusion chromatography, Western and Northern blotting to investigate the subcellular distribution of hepatic copper, the association of the metal with hepatic copper binding proteins and the expression of specific mRNAs for copper binding proteins in liver tissue from two patients with Wilson's disease, two patients with chronic liver disease and two patients with normal hepatic copper levels. Unlike previous studies the present results fail to show any gross differences in subcellular distribution of copper between the livers, with most of the copper being found in the soluble supernatant where it is associated with metallothionein. Caeruloplasmin mRNA levels were reduced in the two patients with Wilson's disease and also in a patient with fulminant hepatic failure. It remains to be confirmed if the reduction of caeruloplasmin mRNA is specific for Wilson's disease. Levels of mRNAs for copper zinc superoxide dismutase and metallothionein were variable and not related to liver copper. PMID- 1506663 TI - Immunocytochemical localization of histamine in secretory granules of rat peritoneal mast cells with conventional or rapid microwave fixation and an ultrastructural post-embedding immunogold technique. AB - We used a post-embedding immunogold labeling approach to define the fine structural localization of histamine in rat peritoneal mast cells that were fixed using either standard aldehyde fixation or a fast microwave-aldehyde fixation method. Specimens were processed routinely for electron microscopy. Thin sections were exposed first to guinea pig antihistamine antiserum and then to gold conjugated goat IgG directed against guinea pig IgG. By transmission electron microscopy, gold particles were localized to the matrix of cytoplasmic granules. Control sections treated with non-immune sera did not show labeling of mast cells. Adsorption of antihistamine antiserum with purified histamine or histamine bound to agarose showed a significant reduction (p less than 0.005) in granule staining. We also confirmed that our isolation procedures yielded functionally competent mast cells which released histamine when stimulated with sheep anti-rat IgE antiserum or with compound 48/80. These studies define the conditions of fixation for electron microscopy that are appropriate for the localization of histamine in the granule matrix of rat peritoneal mast cells. PMID- 1506664 TI - Localization of lysosomal acid phosphatase mRNA in mouse tissues. AB - We studied the expression of lysosomal acid phosphatase (LAP) in mouse by hybridizing Northern blots and tissue sections with the mouse LAP cDNA. Three mRNA species of 2.3, 3.2 and 5.2 KB were identified, which differ in the length of their 3' untranslated region (UTR). The 3.2 KB mRNA is expressed in equal amounts in all tissues and represents the major species in most tissues, whereas the amounts of the 2.3 and 5.2 KB species differ. In situ hybridization of different tissues of adult mice showed a uniform expression of LAP, as expected for a housekeeping gene, except in testis and brain. In testis we found an increase in the LAP mRNA level in spermatocytes. By Northern blot analysis of young mouse testis, this increase could be attributed to late pachytene primary spermatocytes or secondary spermatocytes. In brain tissue the neurons were predominantly labeled, especially the Purkinje and pyramidal cells, whereas glial cells expressed only low amounts of LAP mRNA. Very high LAP expression was also found in the epithelial cells of the choroid plexus. Analysis of LAP expression during mouse embryonic development between Days 9.5 and 17.5 revealed a prominent expression relative to other tissues in the neural tube from Day 9.5 to Day 13.5. PMID- 1506665 TI - Simultaneous localization of six antigens in single sections of transgenic mouse intestine using a combination of light and fluorescence microscopy. AB - To study the geographic differentiation of the intestinal epithelium and to understand the complex lineage relationships of its cell populations, it is often necessary to visualize the protein products of multiple genes in sections prepared from different positions along the duodenal-to-colonic and/or crypt-to villus axes. Multilabel fluorescence or brightfield immunohistochemical techniques have previously been used for this purpose. However, the number of antigens that can be identified on single sections is limited in fluorescence microscopy by the number of fluorophores with non-overlapping absorption and emission characteristics, in brightfield microscopy by the number of visually distinguishable chromogens, and in both methods by the availability of primary antisera raised in multiple species. We have now used a combination of light and fluorescence microscopic techniques to increase the number of antigens that can be detected in a single section to six. Sections were sequentially stained using immunogold with silver intensification, peroxidase-antiperoxidase with diaminobenzidine chromogen, and peroxidase-anti-peroxidase with alpha naphthol/basic dye as chromogen, followed by simultaneous fluorescent detection with fluorescein, 7-amino-4-methylcoumarin-3-acetic acid, and beta-phycoerythrin. This method enables up to four separate antigens to be visualized within a single cell and two additional antigens to be detected in unrelated cells. The technique is illustrated by examining the cellular patterns of expression of liver fatty acid binding protein/human growth hormone fusion genes in the intestinal epithelium of adult transgenic mice. It should be generally applicable to other experimental systems that require localization of multiple antigens in single tissue sections. PMID- 1506666 TI - Localization of a novel integrin of the beta 1 subfamily in human tissues. AB - We have previously described a novel integrin composed of a beta 1-chain non covalently linked to an alpha-chain which is biochemically different from those known so far (i.e., alpha 1-alpha 7 and alpha v). This molecule has been identified with a monoclonal antibody (MAb) termed 10.1.2 raised against long term cultured human thymic epithelial cells (TEC). In this study we analyzed the immunohistochemical distribution of this new integrin in a variety of human tissues. MAb 10.1.2 stains several types of endothelial and epithelial cells. Among the endothelia, a strong reaction was detected in the HEV of lymphoid organs including thymus, lymph node, tonsil, and mucosa-associated lymphoid tissue. Epithelial localizations of note were those in the basal layer of the epidermis and of other stratified squamous epithelia, where the lateral and apical but not the deep surfaces of most cells were stained. A variety of water electrolyte transporting cells in sweat glands, salivary glands, and kidney were also stained at their deep surface. The latter findings suggest that this molecule may subserve other functions in addition to those related to cell adhesion. PMID- 1506667 TI - A novel fluorescence detection method for in situ hybridization, based on the alkaline phosphatase-fast red reaction. AB - We have used naphthol-ASMX-phosphate and Fast Red TR in combination with alkaline phosphatase (APase) to produce fluorescent precipitated reaction products in a non-radioactive in situ hybridization (ISH) method. To obtain optimal and discrete localization of the strongly red fluorescent ISH signals, the enzyme precipitation procedure was optimized. The optimal reaction time and the concentrations of substrate and capture agent were determined. Furthermore, polyvinyl alcohol (PVA) was used to increase the viscosity of the reaction mixture and thus to reduce diffusion of the reaction product. Our results show that the APase-Fast Red detection method has at least the same sensitivity as currently observed in other immunofluorescent detection systems. A single copy DNA sequence of 15.8 KB could be localized with high efficiency in metaphase spreads and in interphase nuclei. Double labeling procedures, in which the FITC- and azo-dye fluorescence are combined, are also feasible. The red fluorescent ISH signals showed hardly any fading as compared with FITC fluorescence on exposure to either light from the mercury-arc lamp or laser light. Therefore, these red fluorescent signals with a virtually permanent character allow a better analysis and three-dimensional localization of such cytochemically detected genomic fractions by means of confocal scanning laser microscopy as compared with the use of FITC, TRITC, or Texas Red as label. PMID- 1506668 TI - Stereo views and immunogold labeling of the pellicular microtubules at the inner surface of the plasma membrane of Leishmania as revealed by fracture-flip. AB - We used a modification of fracture-flip to reveal the nanoanatomy of the inner surface of the plasma membrane in promastigotes of Leishmania. After freeze fracture, lightly fixed promastigotes were coated with a stabilizing layer of carbon evaporated from an electron gun, thawed, and washed. Fractured promastigotes attached to the carbon casts by the protoplasmic (i.e., inner) halves of their plasma membranes were treated with Triton X-100, followed by exposure to low concentrations of trypsin and thorough washing. This was followed by picking up and flipping of the replicas, followed by air-drying. The actual inner surfaces of the plasma membrane were then imaged by platinum shadowing. Extended, three-dimensional, high-resolution views of the inner surface of the plasma membrane showed parallel arrays of microtubules (average spacing 47 nm) closely apposed to the inner surface. Cytochemical labeling confirmed the morphological identification of both subpellicular and flagellar microtubules, as determined by treatment with mouse monoclonal anti-alpha- or anti-beta-tubulin, followed by labeling with goat anti-mouse IgG adsorbed to colloidal gold. Removal of the microtubules revealed parallel arrays of particles (average diameter 17 nm). We hypothesize that these particles represent the cytoplasmic portion of proteins that link the microtubules to the plasma membrane. PMID- 1506669 TI - A novel modification of the avidin-biotin complex method for immunohistochemical studies of transgenic mice with murine monoclonal antibodies. AB - When mouse tissues are probed with murine monoclonal antibodies (MAb) by indirect immunohistochemistry, the secondary antibody detects tissue-bound MAb and irrelevant, endogenous mouse immunoglobulins. The latter are a source of confounding background, especially in diseased tissues. To circumvent this problem, we generated complexes of primary MAb and biotinylated secondary antibodies in vitro for use as antigen-specific probes. After blocking free binding sites in the complexed secondary antibodies with normal mouse serum, the complexes were applied to mouse tissue sections and tissue-bound complexes were visualized with an avidin-biotin detection system. Complexes formed with 12 different rat or mouse MAb were used to probe sections of normal mice, tumor bearing transgenic mice, and mice with tumor xenografts. The staining patterns produced by these probes reflected the specificity of the MAb in the complexes, and the labeling of irrelevant, endogenous mouse immunoglobulins was reduced substantially. This novel, indirect immunohistochemical method can be exploited to study normal and diseased mouse tissues using a variety of murine MAb. PMID- 1506670 TI - The expression of desmosomal and corneodesmosomal antigens shows specific variations during the terminal differentiation of epidermis and hair follicle epithelia. AB - Using five monoclonal antibodies (MAb), we studied by indirect immunofluorescence the desmosomes and a junctional structure specific to cornified layers, the corneodesmosome, in normal and plantar epidermis and in the various sheaths of the anagen hair follicle. The monoclonal antibodies DP1&2.2-15, PG5.1, and DG3.10, specific for desmoplakins I/II, plakoglobin, and desmoglein I, respectively, were used to study the desmosome antigens, and G36-19 and G20-21 to study the corneodesmosome antigens. The distribution and sequence of expression of the five antigens allowed the nine epithelial differentiation pathways studied to be merged into four distinct families: non-plantar epidermis, characterized by the absence of desmosome and corneodesmosome antigens in the stratum corneum; the outer root sheath of the hair follicle, which behaves like the viable layers of the epidermis with regard to the desmosome antigens but does not express the corneodesmosome antigens; plantar epidermis and the three components of the inner root sheath in which the corneodesmosome antigens are present up to the desquamating layer; and the three components of the hair shaft, which are characterized by the absence of expression of both the desmosome and the corneodesmosome antigens in its mature portion. PMID- 1506671 TI - Isolation of monoclonal antibodies recognizing rat bone-associated molecules in vitro and in vivo. AB - Knowledge of the number and kinds of differentiation steps that characterize cells of the osteoblast lineage is inadequate. To further analyze osteoblast differentiation, we generated a series of monoclonal antibodies (MAb) to osteogenic cells. Spleen cells from mice immunized with whole-cell populations enriched for expression of osteoblast-associated properties or bone formation in vitro were fused with the SP2/0 myeloma cell line. Supernatants from growing hybridomas were screened by indirect immunofluorescence on frozen sections of a portion of 21-day fetal rat heads that included the calvaria bone, periosteum, muscle, fibrous connective tissue, and skin. Six MAb were selected with bone associated staining and limited ability to label other tissues. Either cell surface or cytoplasmic molecules were recognized by five of the MAb; one recognized a molecule detectable both in the cytoplasm, on the cell surface, and in the extracellular matrix. Of the antibodies selected, one identified both preosteoblasts and osteoblasts and has been found to be against alkaline phosphatase. The others recognized the mature osteoblasts, osteocytes, and chondrocytic cells. The pattern and distribution of the labeling in vivo extended to primary cells and cell lines in vivo. These results support earlier observations on molecules differentially expressed by cells at different stages of the osteoblast lineage and extend the available cell surface and cytoplasmic epitopes identifiable as marker molecules. PMID- 1506672 TI - Localization and quantification of epidermal growth factor receptors on single cells by confocal laser scanning microscopy. AB - We have established a method for quantifying binding of fluorescence-labeled growth factors to their receptors on single cells in situ with the confocal laser scanning microscope (CLSM). Biotinylated epidermal growth factor (EGF) coupled to phycoerythrin-labeled anti-biotin was used to compare the levels of fluorescence on three different cell types for which the number of EGF factors was known from Scatchard analysis of [125I]-EGF binding. The results showed that as few as 10,000 receptors/cell were detectable above back-ground. This method will provide a rapid and quantifiable alternative to autoradiography for ligand binding to single cells in situ. PMID- 1506674 TI - Ultrastructural localization of laminin on in vivo embryonic, neonatal, and adult rat cardiac myocytes and in early rat embryos raised in whole-embryo culture. AB - The temporal and spatial distribution of the basement membrane component laminin was examined in vivo in developing rat hearts at 11.5 and 15 days of embryonic development (ED), and in neonates and adults, by pre-embedding ultrastructural immunocytochemistry. In addition, the patterns observed at 11.5 days ED were compared to the distribution of laminin in embryos maintained in whole-embryo culture. At 11.5 days ED laminin was localized in punctate patches on the surface of the plasma membrane, with large gaps between areas of staining. The development of myocytes and localization of laminin in the whole embryo-cultured embryos was similar to that found in the in vivo embryos. At 15 days ED, laminin localization was limited to distinct patches of developing extracellular matrix material associated with the sarcolemma. Gaps between areas of localization were shorter than in the 11.5-day hearts. In neonates, distribution of laminin localization was more extensive with fewer gaps and was associated with the developing basement membrane. In adult hearts, laminin was localized along the entire length of the basement membrane and was heaviest in areas of morphological specialization, such as Z-bands, where collagen bundles contacted the sarcolemma. PMID- 1506673 TI - Detection of gastrin mRNA in human antral mucosa and digestive endocrine tumors by in situ hybridization: a correlative study with immunocytochemistry and electron microscopy. AB - In gastrinomas, as well as in other endocrine tumors whose hormone overproduction is responsible for clinical syndromes, antibodies against the bioactive form(s) of hormones can fail to detect immunoreactivity. Moreover, tumor secretory granule morphology may fail to allow tumor type identification. The use of anti pre-pro-gastrin antibodies has been proposed as an alternative to identify gastrinomas. The aim of the present study was to demonstrate that in situ detection of gastrin mRNA may represent another possibility. A 35S-labeled cDNA probe encoding the human gastrin pre-pro-hormone was used to localize gastrin gene transcripts in antral mucosa and digestive endocrine tumors from patients with a Zollinger-Ellison syndrome characterized by high serum gastrin levels. In situ hybridization was combined with light and electron microscopic immunostaining of the bioactive gastrin 17/34 form and morphological study of secretory granules. Gastrin mRNAs were detected in antral gastrin cells and in a variable proportion of tumor cells in all endocrine tumor studied. Transcript expression correlated well with immunohistochemical staining and granule ultrastructure for most of the tumors, and provided crucial evidence for identifying as gastrinomas two tumors with weak immunoreactivity and poorly granulated cells. Our data show that in situ hybridization is a sensitive method for gastrin mRNA detection and represents a valuable tool for the identification of gastrinomas. PMID- 1506675 TI - Intranuclear localization of phospholipids by ultrastructural cytochemistry. AB - The presence of phospholipids within the interphase nucleus and in isolated chromatin, previously demonstrated by analytical biochemical methods, has been only rarely documented by cytochemical procedures, especially at the ultrastructural level. By means of a gold-conjugated phospholipase technique, we investigated the fine localization of endogenous phospholipids in the different nuclear domains in rat pancreas and in cell cultures. To reduce possible removal or displacement of phospholipids, different specimen preparation procedures such as cryofixation, cryosectioning, and freeze-fracturing were utilized. Apart from slight differences in efficiency among these methods, phospholipids have been cytochemically identified in the same nuclear domains: the interchromatin granules and fibers and the dense fibrillar component of the nucleolus. These results suggest that the phospholipids are an actual nuclear component, not randomly distributed in the nucleoplasm but mainly localized in the nuclear domains involved in the synthesis, maturation, and transport of ribonucleoproteins. PMID- 1506676 TI - The cell cycle of glial cells grown in vitro: an immunocytochemical method of analysis. AB - Studies of cell cycles have traditionally employed [3H]- and [14C]-thymidine to label the DNA of proliferating cells and autoradiography to reveal the thymidine label. The development of antibodies to the thymidine analogue 5 bromodeoxyuridine (BrdU) has allowed the development of an immunocytochemical method analogous to the thymidine autoradiographic technique. In direct comparisons, we found that the immunocytochemical method consistently detected a larger number of proliferating cells. This suggests that it may be a more sensitive index of proliferation than thymidine autoradiography in some systems. We used the BrdU method to analyze the cycle of astroglia cultured from neonatal mouse cerebral cortex. Cells were exposed to BrdU for 1 hr to label a discrete subpopulation of proliferating cells. At 2-36 hr after the pulse, a combination of anti-BrdU immunocytochemistry and counterstaining with propidium iodide was used to identify proliferating cells. The length of the cell cycle was determined by charting the percent of BrdU-labeled mitotic cells vs time after the pulse. We found the average length of the cell cycle of astrocytes grown in vitro to be 20.5 hr. The combined G2 + M phases were 2-3 hr. These values are virtually identical with those found for glial cells in vivo, suggesting that the culture environment does not interfere with the normal control of cell cycle length. PMID- 1506677 TI - An infrared study of the interaction of polymethyl methacrylate with the protein and mineral components of bone. AB - We used Fourier transform infrared (FT-IR) microscopic mapping techniques to investigate the infiltration of polymethyl methacrylate (PMMA), a widely used medium for embedding biological tissues, into rat femur sections. Monitoring of the infrared absorbances of the PMMA carbonyl stretch, the protein amide I, and the apatite mineral phosphate stretch over a 225 x 975-microns region of the epiphyseal growth plate region of the rat femur enabled comparison of the relative amount of each component in distinct regions of the tissue. It was found that PMMA penetrates less into regions of greater mineral density and that the frequency of the PMMA carbonyl absorbance from the embedded tissue, 1729 cm-1, is identical to the free PMMA carbonyl frequency. This is consistent with a diffusion mechanism of infiltration of the PMMA, with no specific chemical interaction between the PMMA and the tissue components. PMID- 1506678 TI - A simple enhancement method for the silver-gold-intensified diaminobenzidine reaction in the light microscopic immunoperoxidase technique. AB - We describe a simple and sensitive method for enhancement of the silver-gold intensified 3,3'-diaminobenzidine (DAB) reaction demonstrating peroxidase activity. After completing silver-gold intensification of the preparations immunostained by the avidin-biotin-peroxidase method with DAB as the chromogen, the preparations were immersed in a solution containing uranyl nitrate. This new method appeared to increase the sensitivity by at least one order of magnitude as compared with silver-gold intensification alone. PMID- 1506679 TI - Immunophenotyping and molecular cytogenetics. PMID- 1506680 TI - Tcl-30, a new T cell-specific gene expressed in immature glucocorticoid-sensitive thymocytes. AB - Glucocorticoid treatment induces programmed cell death (apoptosis) in susceptible T lymphocytes. We have previously isolated and characterized 13 genes induced by agents that cause apoptosis in the murine thymoma cell line, WEHI-7TG. One of these genes, now designated Tcl-30, encodes a 2.4-kb mRNA that is specifically expressed in thymus. Sequence analysis of a full-length cDNA for Tcl-30 reveals a potential open reading frame of 454 amino acids that shares sequence identity to a human placental-specific protein of unknown function, PP11. The putative protein encoded by Tcl-30 also contains a cysteine-rich somatomedin B-like domain found in vitronectin, PP11, and the plasma cell membrane glycoprotein, PC-1. Subpopulations of murine thymocytes sorted on the basis of their expression of the CD4, CD8, and surface heat-stable Ag (HSA) were analyzed by an RNase protection assay to determine the expression of Tcl-30 as a function of T cell development. Tcl-30 was expressed exclusively in the HSA+ T cell populations (CD4 CD8-HSA+; CD4+CD8-HSA+; CD4-CD8+HSA+; and CD4+CD8+HSA+) and not in the HSA- single positive T cell populations (CD4+CD8- or CD4-CD8+) of the thymus or spleen. Therefore, we conclude that Tcl-30 expression is lost during T cell maturation and is absent at the most mature stages of T cell development. The function of Tcl-30 is unknown; however, the CD4+CD8+ double-positive subpopulation expressing Tcl-30 represents thymocytes destined to undergo massive intrathymic cell death. The possibility that Tcl-30 expression may define a population of T lymphocytes that is sensitive to glucocorticoid-mediated apoptosis is discussed. PMID- 1506681 TI - Immortalization of murine B cells in vitro with oncogene-containing retroviral vectors. AB - A large panel of oncogene-containing retroviral vectors has been constructed and used to infect activated murine splenic B cells to determine whether particular oncogenes are capable of directly mediating B cell immortalization. Mature B cell lines have been consistently established with some of these retroviral vectors. These B cell lines arose at a low frequency, indicating that more genetic events were required in addition to infection with the retroviral vector for immortalization to occur. All such lines were LPS-dependent and non-tumorigenic. All lines secrete IgG and express surface IgG, but not IgD or IgM. In addition, they are CD11b+ and CD23-. These cells may be derived from the CD5 "lineage" or a related B cell subset and appear to be more susceptible to immortalization than conventional B cells. PMID- 1506682 TI - The MB-1/B29 heterodimer couples the B cell antigen receptor to multiple src family protein tyrosine kinases. AB - The B cell Ag receptor complex is comprised of membrane (m)IgM or mIgD noncovalently associated with one or more heterodimers, each containing one subunit of MB-1 (IgM alpha or IgD alpha) and one of B29 (Ig beta or Ig gamma). It is known that cross-linking of the B cell Ag receptor results in protein tyrosine kinase activation. Recent reports from other laboratories have demonstrated that mIg coprecipitates with multiple src family protein tyrosine kinases, including blk, lyn, and fyn. However, the mechanism by which these kinases are physically coupled to the Ag receptor has not been confirmed. It has been hypothesized that the mIg-associated proteins MB-1 and B29 provide a physical link between the Ag receptor (mIg) and one or more protein tyrosine kinases. In this study, we confirm previous findings demonstrating that the B cell Ag receptor coprecipitates with the MB-1/B29 heterodimer as well as the protein tyrosine kinases blk, lyn, and fyn under mild detergent conditions (1% digitonin). Additionally, we demonstrate that in detergent conditions (1% Nonidet P-40 (NP 40)) which disrupt the association between mIg and the MB-1/B29 heterodimer, no protein tyrosine kinase activity can be detected in association with mIg. These findings indicated that NP-40 effectively dissociates the B cell Ag receptor from ancillary signal transducing proteins. MB-1 and B29 were however, found to coprecipitate with blk, lyn, and fyn isolated from B cell lysates containing 1% NP-40. No significant difference was observed in the stoichiometry of association between the kinases and the MB-1/B29 heterodimer in the presence of 1% NP-40 when compared to 1% digitonin. It was further determined that in resting B cells, only a small fraction (approximately 1-3%) of the MB-1/B29 heterodimers appear to be complexed with protein tyrosine kinases. Finally, based on preclearing experiments, it appears that individual heterodimers may associate with a single species of protein tyrosine kinase. These data support the hypothesis that the MB 1/B29 heterodimer couples the antigen receptor to protein tyrosine kinases, thereby providing a physical link that facilitates Ag receptor-mediated regulation of kinase activity. PMID- 1506683 TI - Expression of Mls determinants in mice exhibiting the severe combined immunodeficiency (scid) mutation or X-linked immunodeficiency (xid) defect. AB - While Ig+ B cells appear to be the principal cell type expressing immunogenic minor lymphocyte stimulatory (Mls) determinants, both T cells and B cells are capable of mediating deletion of developing Mls-reactive thymocytes. In addition, levels of mouse mammary tumor proviral transcripts are increased after B or T cell stimulation, and expression of functional Mls determinants is augmented by activation of B cells. These findings suggest Mls determinants are present on B and T lymphocytes, and that activation of B and T cells augments Mls expression. In the present study, we wished to determine whether B and T cells were required for expression of Mls determinants by examining mice with severe combined immunodeficiency (SCID) containing no detectable Ig+ B cells or TCR+ T cells, as well as animals that expressed the X-linked immunodeficiency (xid) defect and lacked a subset of mature B cells. We found Mlsa-reactive V beta 6hi T cells were deleted from thymi of male (CBA/NxAKR/J)F1 xid mice, and that spleen cells from these animals stimulated anti-Mlsa mixed lymphocyte responses by unprimed B10.BR spleen T cells. In addition, Mlsc-reactive V beta 3hi AKR/J thymocytes and spleen T cells were deleted in AKR/J----SCID bone marrow chimeras, and spleen cells from SCID mice stimulated proliferation by an Mlsc-specific T cell clone. These results demonstrate that both xid mice and SCID animals express Mls determinants that mediate deletion of developing, Mls-responsive thymocytes and stimulate proliferation of mature, Mls-reactive T cells. Hence, mature B cells and T cells are not essential for Mls expression. PMID- 1506684 TI - Beta-chain broadens range of CD8 recognition for MHC class I molecule. AB - It is known that the alpha-chain of CD8 binds to a negatively charged loop composed of residues 223 to 229 on MHC class I Ag and that binding of CD8 alpha enhances Ag recognition of T cells. We have recently shown that the mouse CD8 alpha homodimer does not bind to either the HLA class I alpha 3 domain or a mutant of H-2Kb Ag containing a substitution of glutamine for methionine at residue 224, which brings this residue toward the human consensus. Here we report a complementary study of the CD8 beta-chain. The functional role of the CD8 beta chain was analyzed by using four T cell hybridoma lines expressing mouse CD8 alpha and transfected with the mouse CD8 beta gene. As compared with the lines expressing only CD8 alpha, allorecognition of the chimeric H-2Kb Ag that contains the HLA class I alpha 3 domain was enhanced in lines expressing both CD8 alpha and -beta. This enhancement was blocked by either anti-CD8 mAb or anti-HLA class I alpha 3 domain mAb. In addition, we show that CD8 alpha beta binds the H-2Kb mutant Ag at residue 224. These results suggest that the beta-chain allows the CD8 alpha beta heterodimer to recognize the chimeric H-2Kb Ag. A model for the role of the beta-chain is presented. PMID- 1506685 TI - Molecular cloning of the NK1.1 antigen, a member of the NKR-P1 family of natural killer cell activation molecules. AB - In mice, the NK1.1 alloantigen is expressed on all NK cells and it initiates transmembrane signals that activate cytotoxicity. NK1.1 has been mapped to a chromosomal region that encodes two families of receptor-like molecules, the NKR P1 family and the Ly-49 family. Both of these gene families encode type II integral membrane proteins whose extracellular domains are homologous with known C-type lectins. We have isolated and expressed a member of the NKR-P1 gene family (mNKR-P1.9) and have demonstrated both by immunofluorescence and by immunoprecipitation that this cDNA encodes NK1.1. These findings, which demonstrate the receptor-like structure of NK1.1, will facilitate studies regarding the role of NK1.1 in natural killing and regarding the identification of possible NK1.1 ligands. PMID- 1506686 TI - Isolation and characterization of cDNA clones for mouse Ly-9. AB - We describe the production and characterization of a mouse mAb, S-450-33.2, recognizing the Ly-9.2 specificity. This mAb was used to purify Ly-9 molecules from lymphoid cell lines, and the amino-terminal amino acids were determined. The mAb was also used in a eukaryotic expression system, to isolate cDNA clones encoding Ly-9. Analysis of RNA showed that Ly-9 expression is lymphocyte specific, as determined by the presence of a single hybridizing 2.4-kb species found only in lymphoid cells. Genomic DNA analysis indicated that Ly-9 is encoded by a single-copy gene of 10 to 15 kb. The predicted polypeptide belongs to the Ig superfamily of cell surface molecules with four extracellular Ig-like domains, i.e., a non-disulfide-bonded V domain, a truncated C2 domain with two disulfide bonds, a second non-disulfide-bonded V domain, and a truncated C2 domain with two disulfide bonds (V-C2-V-C2). The sequence data also support the view that Ly-9 belongs to the subgroup of the Ig superfamily that includes Bcm-1, CD2, and LFA 3. PMID- 1506687 TI - Characterization of germ-line genes of the VGAM3.8 VH gene family from BALB/c mice. AB - Five germ-line genes of the VGAM3.8 VH family in BALB/c mice have been isolated from genomic libraries and sequenced. The genes are functional and three are expressed in antibodies of different specificities. Overall nucleotide sequence homologies within the family are greater than 90%, whereas homologies with other VH families are less than 70%. Southern blot hybridization and sequencing indicate a minimum family size of six genes. Differences in the coding regions are mostly confined to CDR, where there is a high replacement/silent substitution ratio, indicative of positive selection for diversification associated with Ag binding. VHVGAM3.8 sequences are highly conserved, and polymorphism in the coding regions appears to be very limited. Evidence is presented that the family has evolved, and been homogenized, by recombinatorial events. PMID- 1506688 TI - Evidence for IFN-gamma as a mediator of the lethality of endotoxin and tumor necrosis factor-alpha. AB - Current evidence indicates that endogenously produced peptide cytokines, most notably TNF-alpha and IL-1, mediate the lethality of experimental endotoxemia. Because circulating serum levels of IFN-gamma can be detected soon after TNF alpha and IL-1 in response to endotoxin, we investigated the role of IFN-gamma in endotoxin and TNF-alpha lethality. Specific neutralizing antibodies to murine TNF alpha (anti-TNF-alpha Ab) or murine IFN gamma (anti-IFN-gamma Ab) produced in our laboratory protected mice against the lethality of Escherichia coli endotoxin (LPS) administered 6 h later. Serum IFN-gamma levels 2 h after i.v. LPS were lower in mice treated with anti-TNF-alpha Ab compared to mice that received nonimmune IgG (median less than 2.5 vs 3.0 U/ml, P2 less than 0.05). In contrast, serum TNF-alpha levels 1 h after i.v. LPS peaked more than fourfold higher in mice treated with anti-IFN-gamma Ab compared to controls (median greater than 6400 vs 1405 pg/ml, p2 less than 0.05). Doses of TNF-alpha (300 micrograms/kg) and IFN-gamma (50,000 U) which were well tolerated when given individually were synergistically lethal in combination (0% lethality vs 100% lethality, P2 less than 0.001), and were associated with higher serum levels of IL-6 than with either cytokine alone. Anti-IFN-gamma Ab provided complete protection against exogenous human rTNF-alpha at the LD100 dose (1400 micrograms/kg, p2 less than 0.001), and in fact prevented lethality at doses four- to fivefold greater than the LD100 human rTNF-alpha (up to 6000 micrograms/kg). We conclude that IFN-gamma is synergistic with TNF-alpha, is essential for the lethality of LPS and TNF alpha, and may have modulating effects on the negative control of serum levels of TNF-alpha after LPS in mice. PMID- 1506689 TI - Analysis of role of CD8+ T cells in resistance to murine AIDS in A/J mice. AB - The mixture of retroviruses termed LP-BM5 murine leukemia virus (MuLV) contains a replication-defective genome (BM5def), the crucial element for induction of murine AIDS (MAIDS), as well as helper B-tropic ecotropic and mink cell focus forming MuLV. Among Fv-1b mouse strains, C57BL mice are sensitive to infection by these viruses and to development of MAIDS, but A/J mice are highly resistant to all viral components and to induction of disease. Inasmuch as previous genetic studies indicated a major role in susceptibility for the H-2D locus within the MHC, the effect of CD8+ T cells in A/J resistance to MAIDS was analyzed by depletion of this subset using mAb. A/J mice treated with anti-CD8 mAb beginning soon after inoculation with LP-BM5 MuLV developed disease within 5 wk after virus inoculation. Histopathologic and flow cytometry alteration of tissues and cells from the mAb-treated mice were identical to those seen in virus-infected MAIDS sensitive strains, and assays for MuLV demonstrated high-level expression of ecotropic MuLV and integration of BM5def. Parallel studies of A/J mice treated with anti-CD4 mAb after infection revealed enhanced expression of ecotropic MuLV but no integration of BM5def, and no signs of MAIDS were detected. These observations indicate that CD8+ T cells are critical in the resistance of A/J mice to LP-BM5 MuLV replication and development of disease and suggest that CD4+ T cells play a role in regulation of ecotropic virus replication. PMID- 1506690 TI - Phospholipase activation during monocyte adherence and spreading. AB - Phospholipase activation is an important element in cellular signal transduction. In our study we investigated the role and regulation of phospholipase activation during human monocyte adherence and spreading. In human monocytes, phospholipase inhibition (with bromophenacyl bromide (BPB) or manoalide) impaired cell adherence and spreading. In contrast, neither cyclooxygenase/lipoxygenase inhibition nor platelet activating factor receptor blockade affected these responses. The impaired adherence and spreading induced by phospholipase inhibition with BPB could be partially reversed by the addition of nM levels of arachidonate (20:4(n - 6)). Dihomogammalinolenic acid (20:3(n - 6)) could substitute for arachidonate, but other polyunsaturated fatty acids were ineffective in this regard. The phospholipase inhibitor, BPB was selective in its effects on cellular phospholipase activities. BPB inhibited adherence/spreading related and PMA-stimulated phospholipase activities, but not Ca2+ ionophore stimulated phospholipase activity. To further probe for the role of Ca2+ in monocyte adherence and spreading, monocytes were loaded with MAPTAM (bis-(2-amino 5-methylphenoxy)-ethane-N,N,N',N', tetraacetic acid tetraacetoxymethyl ester), an EGTA analog. In contrast to phospholipase inhibition, intracellular Ca2+ chelation with MAPTAM did not affect monocyte adherence but did inhibit monocyte spreading. MAPTAM partially inhibited adherence/spreading-stimulated phospholipase activity, but did not inhibit PMA-stimulated phospholipase activity. These data suggest that human monocyte adherence and spreading may sequentially activate Ca(2+)-independent and then Ca(2+)-dependent phospholipases to release arachidonate. The activation of phospholipase and the release of arachidonate appear to be integral parts of the adhesion process. PMID- 1506691 TI - Platelet-activating factor as an intercellular signal in neutrophil-dependent platelet activation. AB - The role of platelet-activating factor (PAF) in heterotypic cell to cell interactions in a rabbit neutrophil-platelet mixture model was investigated. Platelets were exposed to each of three chemotactic agonists: PAF, leukotriene B4 (LTB4), or FMLP. Only PAF stimulated aggregation, [3H]serotonin secretion, and cytosolic Ca2+ mobilization in platelets alone. However, platelets were stimulated by LTB4 and FMLP in the presence of neutrophils. This neutrophil dependent platelet activation was blocked by pretreatment of platelets with PAF receptor antagonists, and was prevented by desensitization of platelets to PAF. Furthermore, the time-course of platelet activation showed a positive correlation with PAF production by neutrophils stimulated with either LTB4 or FMLP. The PAF mediated neutrophil-platelet interaction was dependent on direct cell to cell contact, as demonstrated by experiments in which the majority of newly formed PAF was neutrophil associated (rather than released). Platelet activation did not occur when the neutrophil-platelet mixture was not stirred, minimizing cell to cell contact, or when platelets were challenged with a cell-free supernatant prepared from neutrophils activated with LTB4 or FMLP. Finally, the neutrophil platelet interaction was abolished by SC-49992, a peptidomimetic of the fibrinogen binding sequence Arg-Gly-Asp-Phe, indicating a Arg-Gly-Asp-specific recognition mechanism. Our results demonstrate that neutrophil-generated PAF plays a crucial role in neutrophil-dependent platelet activation in this model system. This type of intercellular signaling event may be important in certain inflammatory or thrombotic processes. PMID- 1506692 TI - Human low molecular weight B cell growth factor induces surface IgM+/A- B cells to express and secrete IgA. AB - The regulation of Ig class expression has been a controversial area of research. It is well established that T cells, and/or their products, influence which Ig isotype is produced during an immune response. In this study the regulation of Ig secretion of activated human IgM+/A- B cells was examined. Human T cell supernatants induced PWM-activated IgM+/A- B cells to switch to IgA secretion. Purification of the lymphokine mediating this effect involved hydroxylapatite, ion exchange, and gel filtration chromatography. The purified lymphokine could induce switch of IgM+/A- B cells, and it was also capable of inducing proliferation of Staphylococcus aureus Cowan 1 strain (SAC)-activated IgM+/A- B cells. SDS-PAGE and isoelectric focusing indicated the protein mediating this activity had a molecular mass of approximately 14 kDa and a pI of 6.8. These results suggested that the observed activity might be due to low m.w. B cell growth factor (LMW-BCGF), a lymphokine which is capable of inducing proliferation of SAC-activated B cells and has a molecular weight and pI value in the range of the purified protein. Indeed, rLMW-BCGF was able to switch IgM+/A- B-cells to IgA expression and secretion as well as induce the proliferation of SAC-activated IgM+/A- B cells. These results demonstrate that LMW-BCGF is capable of inducing PWM-activated IgM+/A- B-cells to switch to IgA possibly by providing a proliferation signal which induces clonal expansion of IgM+/A- B cells, the progeny of which express a range of isotypes including IgA. This study also demonstrates that lymphokine induced isotype switching involves an intermediate stage of B cell development where human B cells coexpress IgM and a downstream isotype on their surface. PMID- 1506693 TI - Development of the B cell anti-DNA repertoire in (NZB x NZW)F1 mice. Relationship with the natural autoimmune repertoire. AB - The relationship between pathologic anti-DNA and natural autoantibodies (Auto Ab) remains unclear. In particular, it has not yet been elucidated whether pathologic anti-DNA antibodies originate from and are regulated by the pool of natural Auto Ab. To address this question, a large number of Ig-secreting hybridomas were derived from the unstimulated splenocytes of B/W mice, newborn to 12 mo of age, and their binding activities against a panel of self-Ag (DNA, actin, tubulin, myosin, and myoglobin), isotype, idiotypic determinants, and VH gene utilization were analyzed. A progressive increase in the number of Ig-secreting clones was observed and associated with a constant proportion (approximately 6%) of autoreactive B cell clones. However, dramatic changes in the pool of autoreactive B cell hybridomas were observed as the disease evolved, including the selective maintenance of IgM anti-DNA polyspecific antibodies, reduction in percentage of polyspecific IgM mAb with no DNA-binding activity, and the production of IgG anti DNA antibodies of the IgG2 class. The kinetics, immunochemical properties, and idiotypic analysis of polyspecific IgM mAb with DNA-binding activity strongly suggest that they belong to natural Auto Ab and constitute the precursors of pathologic IgG anti-DNA antibodies. In addition, and IgM polyspecific antibody was demonstrated to bind IgG anti-DNA mAb through F(ab')2 interactions suggesting a regulatory role of natural antibodies and their participation in the control of pathologic Auto Ab production. PMID- 1506694 TI - [Estimation of peripheral metabolism under cardiopulmonary bypass by measuring ketone bodies, lactate, and pyruvate]. AB - Both ketone body ratio (KBR) and pyruvate/lactate ratio (P/L) are metabolic indicators related to NAD-linked dehydrogenase system according to the REDOX THEORY. In order to estimate the peripheral metabolic state under the cardiopulmonary bypass (CPB) which is considered to be a moderate and controllable shock state, we measured the pyruvate (P), lactate (L) and ketone bodies (acetoacetate [ACA], 3-hydroxybutyrate[HOB]) pre, during, and post-CPB in 20 open heart surgical patients (Group 1). We also measured ketone bodies in another group (Group 2: 22 patients) of elective coronary artery bypass surgery (CABG). Five patients in Group 2 who developed postoperative organ failure (Group 2-A) were compared with the other 17 cases with uneventful postoperative course (Group 2-B). In Group 1, P and L concentrations progressively increased until the end of CPB, thereafter decreased (P less than 0.001). HOB and TKB significantly increased immediately after the start of CPB, afterward which declined during CPB and returned to the control level after CPB. Both KBR and P/L regression analysis reveal the significant correlation between P/L and KBR (r = 0.51, P less than 0.001). KBR at 1 hour after CPB returned to the control level, however, P/L at 1 hour after CPB still stayed in the significant lower level than the control (P less than 0.001). KBR at the aortic declamping in group 2-A was significantly lower than that in group 2-B. In conclusion, P/L and KBR changed in relation to hemodynamic change during CPB.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1506695 TI - [Experimental study on hemodynamic and cardiac effects of counterpulsatile blood flow assisted IABP for acute left ventricular failure]. AB - The purpose of this study is to evaluate the effect of newly developed balloon pumping system with synchronized blood flow assist for acute left ventricular failure. In 21 mongrel dogs with left heart failure following left coronary artery ligation, counterpulsatile flow assisted IABP (CFA-IABP) was instituted changing the flow rate from 5% to 70% of the aortic flow at control. The following results were obtained. 1) CFA-IABP significantly increased aortic, carotid, and coronary sinus flows as well increased aortic pressure and endocardial viability ratio, and also reduced left atrial pressure, LVEDP and myocardial oxygen uptake at the low flow assist of about 20% of aortic flow at control. 2) In high flow assist of more than the 50%, the effect of CFA-IABP was present but limited. 3) There was no change of hemodynamics and cardiac function at the timing of CFA method during the diastolic phase. 4) There was no statistically significant difference between CFA and constitute (non-pulsatile) flow assist, but CFA tended to much improve hemodynamics and cardiac function. PMID- 1506696 TI - [Surgical treatment of native valve endocarditis]. AB - Twenty eight patients with native valve endocarditis (NVE) were subjected to this study. Thirteen patients underwent an operation at the chronic phase, and 15 patients at the active phase. One of the 13 patients at the chronic phase died of cardiac rupture due to myocardial infarction which had occurred preoperatively, and one of 10 patients at active phase without annular infection died of rupture of mycotic cerebral aneurysm early postoperatively. Among 5 patients at the active phase with annular infection, prosthetic valve endocarditis occurred in one patient 1.5 months after supraannular aortic valve replacement, and the second operation with a translocation technique was needed. This patient was lost from low output syndrome. Another patient in this group, who underwent a translocation technique because of mycotic annular abscess, died of intestinal infarction late postoperatively. The other 24 patients went a good postoperative course. Five patients with annular infection at the active phase had a shorter duration from the infectious onset to operation (20 days to 2 months, average 38 days), and the causative microorganisms were streptococcus faecalis, staphylococcus epidermidis and gram-negative coccus. One patient, who died of mycotic cerebral aneurysmal rupture, had candida albicans as a causative microorganism. For patients with NVE, an early aggressive operation is essential before infection extends to the annulus or to other vital organs, especially when these microorganisms are identified. PMID- 1506697 TI - [Left atrial myxomas: clinical characteristics, evaluation and considerations in classifying tumors]. AB - Eleven patients underwent surgical excision for left atrial myxomas. Clinical symptoms, coronary angiographic findings and operative procedures were evaluated. Myxomas were classified into two types based on macroscopical findings, and clinical characteristics of these two types were analyzed. Seven cases (64%) classified as "lobular-type myxomas" were seen as lobulated, gelatinous and fragile. Four cases (36%) were classified as "round-type myxomas" were round and elastic soft. Primary symptoms included dyspnea on exertion in five cases (45%) and neurological disturbances in six cases (55%). Brain emboli were found in four patients by CT scan, and were classified as lobular-type myxomas. These eleven myxomas successfully removed in all cases. Four of these myxomas, which were pedunculated with fine fibrous stalks, were shaved along the base at the atrial septum or free wall. Others were excised completely along with a portion of the adjacent septum. Microscopic examination of the operative specimens revealed that two lobular-type myxomas with broad-based attachment to left atrial septum had invaded the atrial septum. All patients are doing well and have had no signs of myxoma recurrence at postoperative periods ranging from 10 months to 12 years (mean follow-up 5.3 years). Seven patients underwent selective coronary angiography due to a diagnosis of a coronary artery disease. All coronary angiograms were normal in all cases. In five (71%) of these seven, abnormally dilated atrial branches were seen as supplying the tumor. In two cases with round type myxomas, neovascularity was evident and was made up of clusters of tortuous vessels with tumor blush.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1506698 TI - [Re-evaluation with abridged life tables of the prognosis of lung cancer patients who underwent surgical therapy]. AB - Some lung cancer patients after surgical treatment die as a result of pneumonia or cardiac failure without recurrence of lung cancer months or years after surgery because many such patients are aged or have decreased lung function. Surgical treatment may be partly to blame for these deaths. In this article, to evaluate the contribution of surgical treatment to deaths resulting from other disease, we calculate predicted survival rates using abridged life tables and compute relative survival rates. From 1952 to 1985, a total of 1289 lung cancer patients underwent surgical resection of lung cancer in our department. We calculated some kind of survival rates according to age, stage, and operative procedure. Each case was classified according to age (5-year periods), year of operation (5-year periods), and sex. The 5-year survival rate indicated by the abridged life tables in each class was regarded as the 5-year predicted survival rate of the case. The mean of 5-year predicted survival rates of all cases in a group was regarded as being the 5-year predicted survival rate of the group. The ratio (actual survival rate of the group/predicted survival rate of the group) was also calculated. The ratio of the patients who had stage O, I, or II diseases tended to decrease according to age. This fact supposed that the number of deaths resulting from other diseases with no recurrence of lung cancer in which surgical treatment contributed to death increased in the elderly. In the other hand, this tendency did not exist in the patients who had stage IIIA diseases. PMID- 1506699 TI - [Coronary artery bypass grafting in patients with poor left ventricular function using retrograde continuous cold blood cardioplegia]. AB - Patients with poor left ventricular function or those requiring urgent surgery may have more extensive ischemic myocardial injury if myocardial preservation is incomplete. We have performed coronary artery bypass grafting (CABG) aimed at complete revascularization in such cases using RC-CBCP, which is considered more effective on myocardial preservation during aortic cross-clamping in particular to protect ischemic area distal to severe coronary artery stenosis or obstruction. In the present study, in 25 patients with poor left ventricular function (left ventricular ejection fraction; LVEF less than or equal to 0.3) including 10 patients who required urgent surgery, the operative results were evaluated. All the distal and proximal anastomoses of grafts (average 2.5 grafts) were completed during one aortic cross-clamping using RC-CBCP, therefore graft flow was obtained immediately after release of the aortic clamping. Though this method required 142 minutes of a mean aortic cross-clamping time, myocardial protection was considered to be preferable judging from postoperative isoenzymatic evaluation and improved ventricular function. Fifteen patients with elective CABG were all alive and restored to NYHA class I to II. Among 10 patients requiring urgent CABG, 4 patients with acute myocardial infarction died but others were restored to NYHA class I to II. We conclude that it is important to aim at complete coronary revascularization in patients with poor left ventricular function and RC-CBCP achieves more effective myocardial protection during CABG in the patients. PMID- 1506700 TI - [Delayed sternal closure after cardiac surgery]. AB - Following cardiac surgery, approximation of sternum will produce systemic hypotension or elevation of left atrial and central venous pressures. A new criteria for delayed sternal closure is proposed. Sternal closure has to be delayed when mean left atrial or central venous pressures increased over 2 mmHg at the tentative closure. In seven cases (3.5%) of consecutive 201 patients was delayed the sternal closure under the above mentioned state, all survived and received the successful closure later. One of them died of congestive heart failure four months after the operation and one died of the rupture of the ascending aortic pseudoaneurysm eleven months after the initial operation. Microbiological examination of the mediastinal and pericardial contents obtained at the final sternal closure were negative in all cases. Comparing the total cardiopulmonary bypass time, ventricular fibrillation time, and myocardial ischemic time between in the secondary closure group and in the primary closure group, the total bypass time and the ventricular fibrillation time of the former were significantly longer than the latter, but the ischemic time revealed no difference. In conclusions, persistent elevation of left atrial or central venous pressures after cardiac surgery at the tentative sternal closure seems the reliable predictor for the delayed closure of the sternum. Careful post-operative management prevents serious mediastinal infection. Delayed sternal closure is preferable procedure for the patient with brittle hemodynamics after open heart surgery. PMID- 1506701 TI - [Preoperative high CEA level in lung cancer patients: significant of measurement of serum CEA level among preoperative and postoperative course in long time observed patient]. AB - We measured pre- and postoperative CEA level in 330 patients who underwent resection for lung cancer at Kyushu Cancer Center Hospital between 1983 and 1986 using RIA method. There were 93 patients with high preoperative serum CEA level above 5 ng/ml. The interrelationships among preoperative serum CEA level, prognostic factors, outcome, and postoperative change of CEA level were investigated in the 93 patients. Five-year survival rate of patients with preoperative serum CEA level ranging from 5.0 to 10.0 ng/ml (N = 53) was 60.0%, while that of patients with preoperative CEA level over 10.1 ng/ml (N = 40) was 24.6% (P less than 0.05). Recurrent rate was higher in patients with preoperative CEA level over 10.1 ng/ml, especially in those with lung cancer at stages I or II. However, patients with preoperative CEA level about 50 ng/ml, showed good outcome after curative resection. All 12 patients in whom postoperative serum CEA level did not return to normal died within 4 years, indicating that normalization of CEA level is an important factor in prognosis. This study indicates that among lung cancer patients with high serum CEA level, the preoperative CEA level and postoperative change of CEA level are apparently prognostic factors. PMID- 1506702 TI - [Coronary artery bypass surgery in patients with familial hypercholesterolemia]. AB - Coronary artery bypass grafting (CABG) was performed in 48 patients with heterozygous familial hypercholesterolemia (FH). Seventy-nine percent of these patients had three-vessel disease or left main trunk disease. The internal thoracic artery was used for grafting in 26 patients and the right gastroepiploic artery was used in 4 patients. Although no patient died during surgery, one died subsequently from graft-versus-host disease. Graft patency at one month after CABG was 95% in vein grafts, 100% in arterial grafts, and 97% overall. Histological study revealed that arterial grafts in patients with FH had similar structures to those in non-FH patients, without evidence of atherosclerosis. All patients were prescribed anti-cholesterol drugs to control serum cholesterol levels, and 4 patients underwent LDL-apheresis because of poor control. Survival rate at 11 years after CABG was 83% without cardiac death. Cardiac event-free rate in 47 surviving patients was 53% at 10 years after CABG in vein bypass group, 93% at 5 years in the arterial graft group, and 58% at 10 years overall. Results of CABG were as good in FH as in non-FH patients, using arterial grafts and anticholesterol therapy. PMID- 1506703 TI - [A successful case of thoracic aortic aneurysm with mixed cryoglobulinemia]. AB - Cold-reactive proteins, such as cold agglutinins, cryoglobulins, and cryofibrinogens, are reversibly precipitates, or gel, upon exposure to cold temperatures. Cryoglobulins are usually not of importance, but under special conditions, such as surgical hypothermia, hyperviscosity and damage in microcirculation may occur in patients with high plasma concentration of cryoglobulins. Several groups have reported their efforts to reduce further the risks of surgical hypothermia in patients with cold agglutinins, but rarely in patients with cryoglobulins. A 57-year-old woman with thoracic aneurysm, requiring replacement of the ascending aorta and the aortic arch, had mixed cryoglobulinemia (cryocrit 29%) associated with rheumatoid arthritis. Steroids therapy and preoperative plasmapheresis were performed, and cryocrit levels were decreased until 0% before operation. Systemic hypothermia (25 degrees C), hemodilution techniques during cardiopulmonary bypass, and cold crystalloid cardioplegia were successfully employed, and no clinical evidence of microcirculation damage was posed after operation. PMID- 1506704 TI - [A successful repair of concomitant rupture of the interventricular septum and left ventricular free wall after acute myocardial infarction]. AB - A 74-year-old woman had acute anteroseptal myocardial infarction. Tissue plasminogen activator (t-PA) was infused intravenously about five hours later from the onset of myocardial infarction. Six hours after the infusion of t-PA her blood pressure fell suddenly with the appearance of a grade 3/6 holosystolic murmur. There was a prominent step up of oxygen saturation in the right ventricle which indicated the presence of a left-to-right shunt. Intraaortic balloon pumping for the support of cardiac function was ineffective. At the emergent operation concomitant rupture of the left ventricular free wall and interventricular septum was seen and successfully repaired. She could be weaned from cardiopulmonary bypass easily with the aid of the intraaortic balloon pumping. Her postoperative course was uneventful. The postoperative angiography showed good left ventricular wall motion without any residual shunt. PMID- 1506705 TI - [A clinical experience of V-A bypass using a new antithrombotic coating material]. AB - To perform V-A bypass with minimal systemically administered heparin, we used a equipment coated by fluorine-acryl-styrene-urethane-silicone graft copolymer. A 67 year old woman developed right heart failure after CABG was treated for 25 hours on V-A bypass without oxygenator by using this new antithrombotic coating material. During V-A bypass, hemodynamics were stable. Not coagulative nor hemolytic disorder was observed. And she did not suffer from thrombotic nor hemorrhagic complications. Scanning electron microscopy of coated equipment demonstrated only minor deposits on the surface, and morphologic study of platelet was almost normal. By using this new antithrombotic material it is possible to perform V-A bypass with minimal heparinization, thus avoiding the risk of major coagulation complications. PMID- 1506706 TI - [A sharp edge of the fractured ribs caused the aortic injury at body-position change: a case report]. AB - The reported patient was a 37-year-old male, who got a blunt chest trauma by a motor vehicle accident. Chest X-ray and computed tomography of the chest revealed bilateral multiple rib-fractures, pneumo-hemothorax, lung contusions, but no evidence of mediastinal hematoma. Since respiratory distress with a flail chest was observed, the patient was placed on an artificial ventilation, and thoracocentesis were also done on both sides, while the hemodynamics was fairly maintained with blood transfusion. On the 10th hospital day, however, he suddenly fell into a deep shock with the left hemothorax by changing the body position. Emergency thoracotomy demonstrated the laceration of the descending aorta, that was considered to be made by the sharp edge of the fractured left 8th rib, which correspondingly protruded into the thoracic cavity toward the aorta. The repair of the aortic injury and the resection of the rib edges were performed. He was discharged on the 45th hospital day. In cases with a blunt chest trauma, the majority of the causes of the traumatic aortic injury are reported to be "deceleration injury". Although the considered mechanism of the traumatic rupture of the thoracic aorta in this case is extremely rare, it should be taken into a consideration for treatment of the cases with a blunt chest trauma and multiple rib-fractures. PMID- 1506707 TI - [Coronary artery bypass grafting for a patient with hypothyroidism--a case report]. AB - A 59-year-old female who had been treated for hypothyroidism was admitted with angina pectoris and underwent aorto-coronary bypass grafting. On closing of the sternum, there was unexpected bleeding from the suture line between the vein graft and the ascending aorta. Histological examination of the aortic wall revealed sparsity and disruption of elastic fibers and deposition of mucopolysaccharide without any findings of atheromatous change. It is concluded that hypothyroidism can cause histological change of the aortic wall and that surgical procedures involving the aortic wall in patient with hypothyroidism should be avoided if possible. PMID- 1506708 TI - [A case of mediastinal liposarcoma]. AB - Primary liposarcomas of the mediastinum are rare neoplasms comprising only 0.13 0.75% of mediastinal tumors. We report a case of liposarcoma arising in the right posterior mediastinum. A 74-year-old man without symptoms was admitted to our hospital for evaluation of an abnormal shadow on chest roentgenogram. Computed tomogram (CT) and magnetic resonance (MR) imaging revealed a mediastinal tumor. The tumor was surgically removed, and the diagnosis of well-differentiated liposarcoma was established. MR imaging was superior to CT in evaluation of tumor extent, but not in differential diagnosis as liposarcoma or lipoma. PMID- 1506709 TI - [A case of drug-induced esophageal ulcer developed at the esophageal constriction due to the right aortic arch]. AB - A 26-year-old male has a tooth extracted at a dental surgery, and was given 40 mg Froben, as an anti-inflammatory analgesic agent, and ingested one tablet without water. After 2 days, anterior chest pain occurred. Esophagography and endoscopy were performed and multiple esophageal ulcers were confirmed. Esophagography revealed an esophageal stenosis which was considered to be caused by the extramural compression on the oral side of the ulcers. In the chest roentogenography and CT scanning, the right aortic arch was observed. This case was diagnosed as having drug-induced esophageal ulcer developed at the esophageal constriction due to the vascular ring. PMID- 1506710 TI - [Esophageal bypass operation of a patient with esophageal stenosis and esophago bronchial fistula due to lung cancer]. AB - Esophageal bypass operation was carried out for a patient with lung cancer who was not able to take oral feeding, due to esophageal stenosis and esophago bronchial fistula. Stomach was used as a esophageal substitute, through antethoracal route. Abdominal esophago-jejunostomy was performed for drainage of esophago-bronchial fistula. Oral intake of foods was started from 11th postoperative day without major complication. And then, she was permitted to discharge only with a jejunostomal feeding tube. Recently the quality of life is emphasized, even in cases in which curativity of cancer cannot be expected. Surgery in such cases entails many risks and then, special care must be taken to determine the indication and procedure of this operation. In the case herein reported, such attention to detail resulted in survival for over one year. PMID- 1506711 TI - [A case of true aneurysm of the mitral valve associated with torn chordae]. AB - The patient was a 62 year old woman complaining of severe exertional dyspnea. Preoperative echocardiogram demonstrated the abnormal uniform echo of the anterior leaflet of the mitral valve which protruded toward the left atrium in systole as well as in diastole. Severe mitral regurgitation was also detected. The aneurysm of the anterior leaflet of the mitral valve was confirmed during the operation and mitral valve replacement was performed. The postoperative course was uneventful. Pathological examination of the resected aneurysm showed myxomatous degeneration. There were no signs of the inflammatory processes. The aneurysm formation in this case was considered to be due to the myxomatous degenerative changes of the anterior leaflet of the mitral valve. Fifteen cases of true aneurysm of the mitral valve reported in Japan were reviewed. PMID- 1506712 TI - [Surgical treatment of aortic root abscesses using a hand-made valved xenopericardial conduit]. AB - A case is described in which a new treatment was taken to eradicate an aortic root abscess in a 56-year-old man with aortic prosthetic valve endocarditis. Debridement of all apparently infected tissue created left ventricular-aortic discontinuity, involving the orifice of the right coronary artery. A conduit of a diameter of 23 mm was made by hand with a glutaraldehyde preserved xenopericardial graft. A 21 mm St. Jude Medical prosthetic valve was sewn in it at 2 cm to its edge. The hand-made valved conduit was used to reconstruct the left ventricular outflow tract and aortic root. A saphenous vein graft was anastomosed end-to-side to the right coronary arterial system and to the conduit distal to the prosthetic valve. The aortography revealed no aortic regurgitation nor abnormalities of the conduit, such as aneurysm formation, and the coronary arteriography showed a functioning graft 5 months after surgery. PMID- 1506713 TI - [An emergency surgical case of double aortic arch with hemoptysis]. AB - A 78-year-old man was admitted because of hemoptysis. CT and aortogram revealed double aortic arch. Bronchofiberscopy revealed intratracheal hemorrhage which was associated with right aortic arch. An emergency operation was performed to prevent massive intra-tracheal bleeding. The patient underwent ligation of the right aortic arch through median sternotomy. After operation, hemoptysis disappeared and the postoperative course was uneventful. Surgical cases of double aortic arch are rare, especially with critical hemoptysis in aged patients. PMID- 1506714 TI - [A case of hypertrophic pulmonary osteoarthropathy caused by adenocarcinoma of the lung]. AB - A 58 year old housewife with tumor shadow in the right upper lung field on the chest X-ray was admitted. Marked swelling and severe arthralgia of both extremities and soft tissue clubbing of the fingers had been presented for two years prior to admission. The radiographs and bone scintigrams indicated proliferating periostitis along the long bones. Bronchofiberscope showed the obstruction of B2a of the right bronchus but the histological diagnosis was not established. Serum level of CEA and IAP were found to be high. Soon after the right upper lobectomy, arthralgia was significantly improved. The histological evaluation revealed a well differentiated adenocarcinoma of a primary lung cancer without mediastinal lymph node metastasis. Within 4 months the serum level of CEA and IAP normalized, the clubbing and the periosteal changes of the bones regressed. PMID- 1506715 TI - [Biosynthesis and possible physiological roles of thiamine triphosphate in animal]. PMID- 1506716 TI - [Structure-function relationship of cytochrome P-450]. PMID- 1506717 TI - [Lactate dehydrogenase subunit deficiencies]. PMID- 1506718 TI - [Purification of transcription factors by using DNA affinity latex particles]. PMID- 1506719 TI - [Actin-myosin motors]. PMID- 1506720 TI - [Phosphatidylcholine breakdown in cellular signal transduction]. PMID- 1506721 TI - [Preparative 2-dimensional electrophoresis--slab NEPHGE/SDS-PAGE]. PMID- 1506722 TI - [The platelet aggregation inhibiting activity in human placenta--study on the ADP degrading activity of human placental villi]. AB - We studied the platelet aggregation inhibiting activity and ADP degrading activity of human placental villi (tissue culture supernatant) and brush border membrane vesicles (BBMV) and obtained the following results. 1. There existed a platelet aggregation inhibiting activity in tissue culture supernatant of villi (S-villi) but not in that of decidua or amnion. The S-villi inhibited the platelet aggregation induced by ADP, but not that induced by collagen, arachidonic acid or ristocetin. And, there was also ADP degrading activity (ADPase activity) in the S-villi. ADP was quickly degraded by S-villi. When ADP was preincubated with S-villi, the platelet aggregation induced by ADP was completely lost. 2. There was very strong platelet aggregation inhibiting activity in placental BBMV. The BBMV almost completely inhibited the platelet aggregation induced by ADP, collagen, arachidonic acid and ristocetin. And there was very strong ADP degrading activity in the placental BBMV. ADP was quickly degraded by BBMV. When ADP was preincubated with BBMV, the platelet aggregation induced by ADP was completely lost. 3. The enzymatic character (heat stability, enzymatic kinetics, Ca++ dependency and pH dependency) of ADP degrading activity in BBMV was very similar to that in S-villi. 4. The ADP degrading activity of both S-villi and solubilized BBMV were fractionated by anion exchange column chromatography and gel filtration column chromatography in similar patterns, and it was shown that ADP degrading substance of both S-villi and solubilized BBMV had a molecular weight of about 60K. PMID- 1506723 TI - [Hematological values in fetal blood by cordocentesis]. AB - Reference ranges for four hematological parameters--hemoglobin, hematocrit, white blood cell and platelet count--in each gestation were established from values for fetal blood samples obtained by cordocentesis from 72 pregnancies at 16-39 weeks gestation. These 72 fetuses turned out as normal or single malformations which should not affect fetal hematological values. Significant correlations were observed between hemoglobin, hematocrit and platelet counts and the number of weeks of gestation. No correlation was found between the white blood cell count and gestational age. Fetal anemia (hematocrit was below the lower limit of the 95% confidence interval) was found in 18 (7%) of all the fetuses that underwent cordocentesis, including nonimmune hydrops fetalis (8 cases), Rh isoimmunization (4 cases), twin-to-twin transfusion syndrome (3 cases), trisomy 18 (2 cases) and autoimmune thrombocytopenia (1 case). Of 26 hydropic fetuses, 8 (31%) were anemic. The prognosis of those fetuses depended on either the gestational age or the severity of the fetal anemia. Our results are useful in diagnosing fetal hematological disorders and to make decisions for fetal therapy. PMID- 1506724 TI - [A biochemical study on the effects of interleukin-6 for premature rupture of membranes]. AB - Chorioamnionitis was thought to be a cause of premature rupture of membranes (PROM). Recently it has been accepted that IL-6 is one of the important cytokines in inflammation. To investigate the correlation between PROM and IL-6, IL-6 production in chorionic cells and amniotic cells was examined. Moreover, the response of these cells to IL-6 was also examined. The results were as follows. 1. Chorionic cells and amniotic cells obtained from human membranes were cultured. 2. Comparing IL-6 production, chorionic cells produced a larger amount of IL-6 (425pg/ml/24 hrs) than amniotic cells (4pg/ml/24 hrs). 3. IL-1 treatment (10U/ml) caused a significant increase in IL-6 release from both chorionic and amniotic cells (43.2ng/ml/24hrs vs. 50.3pg/ml/24hrs, respectively). 4. Lipopolysaccharide (LPS) (10 micrograms/ml) stimulated the release of IL-6 in chorionic cells, but did not affect it in amniotic cells at all. 5. By staining with F actin, it was demonstrated that IL-6 expanded the cellular gap in amniotic cells. 6. After amniotic cells were co-cultured with chorionic cells, IL-1 treatment caused actin-polymerization in amniotic cells. These results suggest that chorionic cells produce a large amount of IL-6 as a result of stimulation by IL-1 or LPS, and the IL-6 produced constricts the amniotic cells. The phenomena may participate in the mechanism of PROM. PMID- 1506725 TI - [Prolactin disorders in patients with habitual abortion]. AB - To evaluate the significance of prolactin (PRL) disorders as one of the etiologic factors in habitual abortion, one hundred and six couples with a history of recurrent spontaneous abortion were assessed clinically and endocrinologically. A high rate of PRL disorders (eight patients with hyperprolactinemia and 31 patients with occulted hyperprolactinemia) was observed (36.8%) in habitual aborters, and only nine of these patients showed clinically detectable luteal insufficiency. These patients who had PRL disorders without luteal insufficiency were further analyzed with immunological examinations. Immunological evaluations revealed that there was no significant difference between the subpopulations of peripheral blood lymphocytes (PBL) in patients with PRL disorders and normal controls while the PHA-stimulated blastogenic activity of PBL and ConA-induced IL 2 synthesis by PBL was slightly suppressed as compared with that of normal controls. And the incidence of HLA sharing in couples with PRL disorders was demonstrated to be higher than that of the normal control couples without abortion. Patients with PRL disorders without impaired corpus luteum function were treated with bromocriptine only, and this therapy was very effective in maintaining pregnancy. The results of this study have allowed us to suggest that PRL disorders might be some of the etiologies in the so called "unexplained" habitual abortion. PMID- 1506726 TI - [Urinary 11-dehydrothromboxane B2 and 6-keto-prostaglandin F1 alpha in normal pregnant women and in women complicated with pregnancy-induced hypertension]. AB - In normal pregnancy, increased production of platelet thromboxane A2(TXA2) parallels increased biosynthesis of vascular prostacyclin (PGI2). An imbalance in the formation of these prostaglandins is believed to be associated with the pathogenesis of pregnancy-induced hypertension (PIH). Recent evidence suggested that aspirin in low doses was effective in reducing the incidence of PIH, by selective inhibition of platelet-derived TXA2 biosynthesis. In this communication, we determined the urinary 11-dehydro TXB2 and 6-keto-PGF1 alpha, which are major metabolites of TXA2 and PGI2, respectively, from early to late pregnancy of normal pregnant women and of women complicated with PIH. The ratio of 11-dehydro TXB2 to 6-keto-PGF1 alpha decreased significantly from as early as 10wks of gestation when compared with that in non-pregnant controls (1.43 +/- 0.15 vs 1.99 +/- 0.13: Mean +/- SEM, p less than 0.05), and increased in later pregnancy to the control values at term. No significant difference was found in the excretion of 11-dehydro TXB2 between normal pregnant women and women with PIH. In contrast, urinary excretion of 6-keto-PGF1 alpha decreased in women with PIH. The ratio of 11-dehydro TXB2 to 6-keto-PGF1 alpha increased significantly as compared with that of pregnant controls. These results demonstrated that disturbed production of vascular PGI2 may be the primary cause of PIH, and affect the vascular responsiveness to pressor inducers such as angiotensin II. PMID- 1506728 TI - [Clinical study of post-term pregnancy]. AB - One hundred fourteen cases of post term pregnancy were clinically analyzed and classified. 1. In case of primipara, the duration of labor was longer and the frequency of prolonged labor (greater than 24 hours) was higher than that of the same number of cases of term delivery at 39 weeks. 2. The main cause of prolonged labor was weak pains. 3. The mean newborn umbilical artery pH in prolonged labor cases was not lower than that in other cases. 4. The cases of post-term pregnancy were classified into 4 groups and compared each other in several respects. Group I: prolonged labor(-), fetal distress(-), vaginal delivery. Group II: prolonged labor(-), fetal distress(+), vaginal delivery. Group III: prolonged labor(-), fetal distress(+), cesarean section. Group IV: prolonged labor(+). 1) The length of the fundus uteri: Group III: minimum after 31 weeks: Group IV: maximum after 35 weeks. 2) The body weight of the newborn and the weight of the placenta: Group III: minimum: Group IV: maximum. 3) The titer of E3 in urine: Group III: obviously low. 4) The frequency of Clifford's sign: Group III: high frequency of meconium staining. Cases of post-term pregnancy were composed of several groups with different clinical features. PMID- 1506727 TI - [Tryptophan and its metabolite concentrations in human plasma during the perinatal period]. AB - The concentration of tryptophan (free and protein bound) and its metabolites in the plasma of the maternal vein and in the umbilical vein, umbilical artery and neonatal vein were determined by high performance liquid chromatography. The plasma levels of tryptophan and most of its metabolites in the umbilical vein and artery were significantly higher than those in the maternal vein. Especially the 3-OHAA level in umbilical blood was approximately 50 times as high as that in maternal blood. The concentration of total tryptophan in the plasma of the neonatal vein showed a marked decrease at one day after birth in comparison with that at birth, but the total kynurenine concentration was not decreased in the plasma of the neonatal vein. In the blood, ratios of free to total tryptophan and kynurenine were kept at a constant level throughout the perinatal period. In conclusion, the present study suggests that tryptophan metabolism may play an important role in fetal development. PMID- 1506729 TI - [A prospective study of psychosomatic reaction to hysterectomy]. AB - Psychosomatic reaction to hysterectomy was prospectively studied by means of psychological tests and a questionnaire. One hundred and twenty patients who had simple hysterectomy were examined before and as long as one year after operation. The mean score for A-state, a state anxiety scale, was high before operation and rapidly declined postoperatively. SRQ-D and CMI, which represent depressive and neurotic states, respectively, showed rather high scores before and 2 weeks after operation. Mean scores in these psychological tests declined to a plateau within 6 months after operation, and there were less psychological and physiological symptoms and there was improved physical activity, showing that most patients can over come psychosomatic problems caused by hysterectomy. A close correlation was observed between the results of psychological tests and the number of psychological symptoms. Forty patients with a high SRQ-D score showed abnormality in other scales. Psychosomatic disorders associated with hysterectomy are characterized by various symptoms but mainly by a depressive state. High SRQ-D patients were divided into three subgroups: A) the SRQ-D score is constantly high, B) the SRQ-D is high for the first several weeks, and C) the score increased after discharge. Patients in each subgroup showed signs of a characteristic personality. These results show the presence of a different psychosomatic approach to the patients personally. PMID- 1506730 TI - [Mass-screening for ovarian cancer by means of transvaginal ultrasonography]. AB - Since April, 1989 in Aomori Prefecture, mass-screening for ovarian cancer by means of transvaginal ultrasonography has been performed in a mass-screening car at the same time mass-screening for uterine cervical cancer. Subjects for this screening were self referred asymptomatic women 30 years of age or older. Real time ultrasonography was performed with a 5-MHz endovaginal transducer 5 sections for scanning were established by means of a transvaginal probe and all ultrasonic pictures obtained were recorded with an 8mm VTR. For women with abnormal ultrasonic findings, such as an ovary (tumor) over 30mm in size and massive ascites, a second screening or accurate examination was performed by retransvaginal ultrasonography, CT-scan, MRI and a combination assay of tumor markers. The results were as follows: The time required for the first screening, including bimanual examination, collection of Pap smear and ultrasonic examination, was about 60-70 seconds. The total number of screened women was 15,282, and 838 (5.5%) of them needed to receive the follow-up examinations. Laparotomy has been done for 48 women to date and 2 women were found to have premalignant and malignant ovarian tumors. PMID- 1506731 TI - [Immunohistochemical study on the expression of epidermal growth factor receptor (EGF-R) in invasive cervical cancer of the uterus]. AB - We have investigated the expression of epidermal growth factor receptor (EGF-R) in invasive cervical cancer tissue of the uterus to determine whether there is a relationship between the expression of EGF-R and lymph node metastasis. Frozen sections of surgical specimens from twenty patients with invasive cervical cancer were immunohistochemically stained by the alkalinephosphatase anti alkalinephosphatase method. The monoclonal antibody 528 we employed reacts with the receptor binding epitope within the EGF molecule, indicating that monoclonal antibody 528 is competitive with ligands such as EGF. Immunohistochemical staining was carried out before and after dissociation of ligands from the cellular surface of the tumor by acid treatment. However, the staining was resulted in no difference between before and after acid treatment. Consequently, the expression of EGF-R was detected in all cancer tissues as well in some normal tissue such as basal cell layers of epidermis. The expression of EGF-R was related inversely with lymph node metastasis by Wilcoxon rank sum test (p less than 0.05). These findings suggest that the expression of EGF-R in cervical cancer does not always lead to tumor growth or tumor invasion, although it does in some types of cancer. PMID- 1506732 TI - [An early detection of the recurrence of serous cystadenocarcinoma of the ovary with the tumor marker CA125 levels]. AB - We studied whether or not, and to what extent, it was possible to predict the recurrence of serous cystadenocarcinoma of the ovary by means of the tumor marker CA125 levels, in 35 treated cases of ovarian serous cystadenocarcinoma. The relationship between the change in CA125 levels and the frequency of recurrence was examined in two groups (recurrent group and non-recurrent group). When CA125 levels over 35U/ml were defined as positive for recurrence, the true positive rate was 22/23 in the recurrent group, and 0 in the non-recurrent group. When this cut-off level was lowered to 30U/ml, and then 25U/ml, the false positive rate in the non-recurrent group was increased to 1/12 and 4/12, respectively. A three-serial increase in CA125 levels was observed at the onset of recurrent cases including two cases with CA125 levels under 35U/ml, while it was not detected in any in the non-recurrent group. Analysis of the CA125 level increase pattern with a non-linear model showed that recurrence could be detected before the CA125 level reached 100U/ml in 13/19 (68.4%) cases if the interval between CA125 measurements was one mouth, and in 17/19 (89.5%) cases if the interval was two weeks. These results suggest that possibility that recurrence can be detected early. PMID- 1506733 TI - [Production of CA125 in cell lines derived from human ovarian carcinoma: in relation to the cell cycle]. AB - The association of the production of CA125 with the cell cycle was investigated in two cell lines derived from human ovarian cancer, one from a serous cystadenocarcinoma (HTOA) and the other from a mucinous cystadenocarcinoma (RMUG s). HTOA and RMUG-s cells secreted CA125 at about 50 and 30U/ml/10(5) cell/24hr, respectively, in the logarithmic growth phase and at about 75 and 100U/ml/10(5) cell/24hr in the steady phase. Analysis by FCM revealed that cultures of both cell lines cultured for 7 days contained more cells in the G0/G1 phase and less cells in the S phase than those cultured for 3 days. The positive rate of immunologically stained DNA polymerase alpha was 31% in HTOA cells and 39% in RMUG-s cells after cultivation of the cells for 3 days. The addition of EGF at 0.01, 0.1 or 1.0nM did not affect the production of CA125 in HTOA or RMUG-s cells while the addition of NaBT at 1, 3 and 5mM raised production in both cell lines as the dose rose. With RMUG-s cells, the addition of EGF at 0.01nM to the culture media accelerated both logarithmic and steady phase growth without a significant change in the production of CA125. In contrast, the addition of NaBT at 1mM suppressed growth, but tended to increase the production of CA125 per cell. With the effect of EGF on the cell cycle of both cell lines, cells in the S phase increased by about 20% as compared with the control, 48 hours after its addition at 0.01nM. In contrast, after cultivation for 48 hours in the presence of 1mM NaBT, cells in the S phase were decreased while those in the G0/G1 phase increased. The results presented above suggested the possibility that some factors other than the cell cycle were involved in the production of CA125. There also is close correlation between cells in the G0/G1 phase and the production of CA125 in the culture of human ovarian cancer cells. PMID- 1506734 TI - [Stimulatory effects of follicular stimulating hormone on the proliferation of ovarian cancer cell line in vitro and in vivo]. AB - The present study was designed to determine the effects of follicular stimulating hormone (FSH) on the proliferation of the human ovarian cancer cell line (HRA line) in vitro and in vivo. The results showed: 1) The number of cells and 3H thymidine uptake significantly increased after FSH treatment, but were suppressed by Buserelin (number of cells: 2.5 +/- 0.4 [con] vs 13.8 +/- 1.7 [FSH] vs 3.0 +/- 0.2 [FSH+GnRHa] x 10(4)/ml, uptake: 1,272.0 +/- 51.5 [con] vs 4,183.4 +/- 114.1 [FSH] vs 885.0 +/- 177.0 [FSH+GnRHa]cpm/10(5) variable cell mean +/- SD, p less than 0.05). 2) FSH increased the proportion of the cells in the S phase but decreased the cells in G0/G1 phase (S: 42.1 +/- 0.72 [con] vs 61.7 +/- 0.5 [FSH], G0/G1: 53.8 +/- 0.4 [con] vs 35.5 +/- 0.6 [FSH]% mean +/- SD, p less than 0.01, t test). 3) Cyclic adenosine monophosphate (cAMP) production by HRA cells was significantly increased by cholera toxin (CTX), but not by FSH (1.29 +/- 0.72 [con] vs 2.05 +/- 0.21 [FSH] vs 16.2 +/- 2.28 [CTX]nM mean +/- SD p less than 0.001), suggesting that FSH has no effects on the adenylate cyclase system in the cell line. 4) FSH and GnRHa receptors were identified in HRA cells, and the number of the receptors was significantly decreased by Buserelin treatment (426.0 +/- 6.8 vs 98.6 +/- 12.3 sites/cell mean +/- SD, p less than 0.05, t test).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1506735 TI - [Development of an experimental model for ovarian cancer invasion using cultured mesothelial cell layer]. PMID- 1506736 TI - [In vitro experiment of transmission of human T-lymphotropic virus type I (HTLV I) to placental villous cells]. PMID- 1506737 TI - [Detection of Chlamydia trachomatis in abdominal cavity using nested PCR]. PMID- 1506738 TI - [Histological and cytological studies of retroperitoneal liposarcoma developing into pelvic cavity]. PMID- 1506739 TI - [Four cases of pregnancy complicated with idiopathic thrombocytopenic purpura (ITP): complete remission of ITP obtained by preoperative high-dose immunoglobulin therapy and splenectomy performed just after cesarean section]. PMID- 1506740 TI - [A case of an acardius in a triplets pregnancy]. PMID- 1506741 TI - [High incidence of vaginal candidiasis in HTLV-I carrier pregnant women]. PMID- 1506742 TI - [A radiological measurements of growing hip joint in 4,000 normal children]. AB - Roentgenograms of 4,000 hip joints of normal children were analyzed. The indices we used were as follows, the YO-value as the standard of growth (half of the distance between the both Y-cartilages), the CO-value as an index of lateralization (the distance between the center line of the pelvis and the center point of the head of the femur), the EO-value as the index of formation of the acetabulum (the distance between the center line of the pelvis and the tip of the acetabular tegmen), epiphyseal height (A), epiphyseal width (B), the alpha-angle, the CE-angle, the Sharp angle etc. The evaluation method we used consisted basically of comparisons made among values indicating length and by which the pelvis showed nearly proportional growth. The correlation coefficient among the YO-, CO-, and EO-values was extremely good. Accordingly, those indices are considered useful for the prognosis of congenital hip dislocation. PMID- 1506743 TI - Metachondromatosis: a report of two cases in a family. AB - We have described a 10-year-old Japanese boy and his father with metachondromatosis characterized by multiple exostoses, enchondromas, and periarticular calcification or ossification and reviewed the literature on this condition. The boy developed bilateral epiphyseal changes in the hips mimicking Perthes' disease. These cases are the first Japanese individuals with this disorder. The natural history and the associated disorders of metachondromatosis are also discussed in this paper. Metachondromatosis is an inherited skeletal dysplasia characterized by multiple cartilaginous exostoses, multiple enchondromas, and periarticular calcification or ossification. The mode of inheritance of the disease is autosomal dominant. In 1971, Maroteaux first described the disorder in 6 patients of 2 kindreds. Since then, 22 cases have been reported. However, no Japanese patient with this disorder has been described to date. We herein report a Japanese boy and his father with this rare bone dysplasia. The boy developed bilateral epiphyseal lesions in the femoral heads mimicking Perthes' disease. PMID- 1506744 TI - Antitumor effect of thermosensitive CDDP-liposomes on human osteosarcoma cells in culture. AB - We have administered cis-diamminedichloroplatinum (II) (CDDP) containing thermosensitive liposome and simultaneous hyperthermia into human osteosarcoma cells (OST) and studied the antitumor effects. Experiments were conducted under the following three different culture conditions as follows, (1) drug treatment alone, (2) hyperthermia after drug treatment, and (3) simultaneous hyperthermia and drug treatment. Antitumor effects were estimated by inhibition of DNA synthesis and decrease in cell growth rates. The antitumor action of simultaneous hyperthermia and drug treatments was the most dominant and synergistic among three experimental conditions. Accumulation of cellular platinum from thermosensitive CDDP-liposomes was markedly enhanced by hyperthermia. Flow cytometric analysis of the cell cycle indicated that CDDP-liposomes only under the simultaneous application of hyperthermia released free CDDP, and evoked cell accumulation in S and G 2/M phase. The results suggested that thermosensitive CDDP-liposomes were not taken up into cells by endocytosis, and released free CDDP into culture media under hyperthermia at 42 degrees C. From these, we have concluded that administration of thermosensitive CDDP-liposomes and simultaneous local hyperthermia could be a promising method for the treatment of osteosarcoma especially in the extremities. PMID- 1506745 TI - [Three-dimensional motion analysis of the wrist using two-directional radiography, with special reference to the motion of the scaphoid]. AB - To clarify the motion of the scaphoid, which exhibits unique movement among the carpal bones, three-dimensional motion analysis of the wrist was conducted. Three fresh-frozen cadavers were thawed, and three-dimensional measurement was carried out using two-directional radiography. Conventional two-dimensional measurement with unidirectional radiography was also carried out for comparison with the three-dimensional measurement. After measurement, the cadavers were dissected and the anatomical findings were correlated with results of measurement. During flexion-extension movement of the wrist, the scaphoid showed flexion-extension movement accompanied by rotation around the longitudinal axis. In radio-ulnar flexion of the wrist, the scaphoid did not exhibit flexion-extension movement in such a way as reported previously, but showed rotation around the longitudinal axis. These results and the anatomical findings suggest that the rotation around the longitudinal axis in both flexion-extension movement and radio-ulnar flexion is the movement along the articular surface of the capitate. PMID- 1506746 TI - [An experimental study on mechanism of cruciate ligament rupture especially on the effect of mechanical property and tensile speed]. AB - Patterns of rupture of the anterior cruciate ligament of the knee are most probably determined by mechanical factors. An experimental study was designed to determine patterns of rupture of the anterior cruciate ligament in immature (young) and fully mature (adult) pig models. Two different methods were used to test disruption forces in young and adult pig knee specimens: quasi-static tension at three different rates using the Instron testing instrument (1000), and impact loading using a specially designed machine. A total of 118 pig test knees was studied. Greater rupture force was required in the adult pigs than in the young pigs. In addition, rupture force was higher with impact loading test than with quasi-static tensile test. In the young pigs, avulsion fracture occurred most commonly in both tests. In the adult pigs, however, mid-substance disruption occurred with quasi-static tensile test and bony avulsion occurred with impact loading test. Patterns of disruption in pig models varies with the relative maturity of the animals tested and mode of force application. A possible explanation for this is the relative strength of the bone and ligament in animals of varied maturity. PMID- 1506747 TI - Stereoscopic vascular architecture of the adult rat femoral head. AB - We studied the micro-architecture of the rat femoral head using a corroding casting method described by Murakami in comparison with haematoxylin-eosin preparation and transparent preparation. Stereoscopic architecture of the microvasculature in the femoral head was finely demonstrated. Vessels in the metaphysis and the epiphysis were aggregated to form a lobular-like structure. The lobules were interconnected with each other by a few capillaries. A bigger vessel probably corresponding to a drainage vein was seen crossing the growth plate. Loop formations, from simple hairpin-like loop to a more complex loop with a glomerular-like aspect, were demonstrated in the metaphysis underlying the growth plate as well as in the articular surface of the epiphysis. PMID- 1506748 TI - [Immunohistochemical localization of interleukin-1 and lipopolysaccharide (LPS) of experimental arthritis in the ankles of rats immunized with LPS extracted from Escherichia coli]. AB - Sprague Dawley (SD) rats were immunized by subcutaneous injections with heat killed E. coli 0:14 and lipopolysaccharide (LPS) extracted from E. coli for 15, 29 and 39 weeks which induced arthritis in the ankle. Localization of interleukin 1 (IL-1) and LPS in the ankle joints were investigated immunohistochemically. Serum IgM rheumatoid factor-like substance (RFLS) and anti-LPS IgM were detected by enzyme-linked immunosorbent assay (ELISA). Rats immunized with LPS for 39 weeks developed synovial lining cell hyperplasia in 25 of 40 ankles and lymphoid cell infiltration in 25 and pannus formation in 23, the rates of which were significantly higher than those of control and rats immunized with LPS for 15 and 29 weeks. The induction rate of arthritis in rats immunized with LPS was the same as that in rats immunized with E. coli. LPS and IL-1 were located in synovial cells and pannus in arthritic joints. Changes of RFLS level in rats immunized with LPS were elevated more gradually than those in rats immunized with E. coli. These findings suggest that LPS could stimulate IL-1 and RFLS production and may induce arthritis in rats resembling rheumatoid arthritis. PMID- 1506749 TI - [Fresh allograft of intact growth plate into immature articular cartilage defects in rats]. AB - In three inbred rat strains with a distinct major histocompatibility complex (MHC), MHC-matched allografts (Fisher, RT1l to Lewis, RT1l, n = 39) or MHC mismatched allografts (Brown Norway, RT1n to Lewis, RT1l, n = 38) of fresh intact cartilage obtained from the tibial epiphyseal growth-plate were grafted into the defects in the femoral articular surface of immature rats. In the controls (n = 72), similar defect on the joint cartilage were made with no epiphyseal plate grafts. The present histological observation was continued throughout one year after transplantation. Total success rate of the repair was significantly better in MHC-matched allografts (92%) than in MHC-mismatched allografts (61%, p less than 0.001) or controls (19%, p less than 0.001). The MHC-matched allografts showed no signs of tissue rejection. However, the MHC-mismatched allografts showed evidence of lymphocyte infiltration and 13 (81%) of 16 grafts were rejected from 12 to 48 weeks after operation. These findings indicate that MHC matched allografts of intact growth-plate have a potential to repair defects in immature articular cartilage over a long period of time, but MHC-mismatched allografts will eventually be rejected. PMID- 1506750 TI - Three-dimensional organization of the cartilage canal--a scanning electron microscopic study by vascular cast of the rabbit's femoral head. AB - The microvasculature of the cartilage canal was studied by plastic corrosion casting using a scanning electron microscopic (S.E.M.) method. At the 25th fetal day, the vascular architecture of the cartilage canal showed an unbranched channel terminated by dividing into a capillary glomerulus. In the later embryonic stage, the canals dilated throughout their course. At birth, before the appearance of the secondary center of ossification, the chondroepiphysis was well vascularized. Anastomosis between the epiphysis and the metaphysis preceded the occurrence of ossification. During the growth stage, the ossifying center was enlarging, the canals extended to the metaphyseal side more frequently than to the articular side. The communicating canals which had traversed the physis faded gradually. In the adult stage, the ossification center had developed completely. The cartilage canals on the surface of the ossification center disappeared. These results show that the cartilage canal has a significant role in the nutrition of the epiphysis and in the osteogenesis of secondary centers of ossification. PMID- 1506751 TI - [Surgical treatment of rheumatoid arthritis]. PMID- 1506752 TI - [Recent advances of diagnosis and treatment of senile osteoporosis]. PMID- 1506753 TI - Effects of some natural products on sugar cataract studied with nuclear magnetic resonance spectroscopy. AB - Four commercial anticataract drugs and five flavonoids isolated from Chinese herbs were studied on their effects to inhibit sugar cataract formation in vitro using 13C-nuclear magnetic resonance spectroscopy (MRS). Pa-Wei-Di-Huan-Wan (PWDHW) and Zhang-Yan-Ming (ZYM) were effective in inhibiting sorbitol formation, whereas Bai-Nei-Ting (BNT) and Pearl Min-Mu-Ye (Pearl MMY) were ineffective in inhibiting sorbitol formation. Among five flavonoids tested, four were moderately effective in inhibiting sorbitol formation, and one was totally ineffective up to 1 x 10(-4)M used. PMID- 1506755 TI - An in vitro comparison of the permeability of prednisolone, prednisolone sodium phosphate, and prednisolone acetate across the NZW rabbit cornea. AB - Controversy and ambiguity in the literature concerning the corneal penetration of prednisolone acetate over Prednisolone Sodium phosphate in NZW rabbits has recently prompted comparative studies using specific chromatographic assays. In vitro, corneal penetration studies were performed using the Ussing Chambers to compare the permeability and flux of both esters and prednisolone at 0.5% using a reversed phase HPLC-UV assay. Chromatograms of samples from the receiver chambers show primarily the presence of prednisolone from both esters; only prednisolone phosphate penetrated the cornea intact. Flux measurements were similar for prednisolone and both salt forms in terms of the metabolite prednisolone. Permeability coefficient calculations give the relative comparison: prednisolone acetate greater than prednisolone greater than prednisolone sodium phosphate. PMID- 1506754 TI - Vascular effects of acetylcholinesterase inhibitors in the rabbit eye: a study with fasciculin and physostigmine. AB - The vascular effects of fasciculin and physostigmine, two acetylcholinesterase inhibitors, were studied with radioactively labelled microspheres in the rabbit eye. In addition, the effects on the intraocular pressure, pupil size and the aqueous humor protein concentration were determined. Both drugs were injected intracamerally in pentobarbital anesthetized and indomethacin pretreated animals. Fasciculin injected in a dose of 0.5 micrograms (0.7 x 10(-10)M) reduced blood flow in the anterior uvea as determined 30 and 60 min after injection. Higher doses had inconsistent effects. Physostigmine injected in a dose of 3 micrograms (1.1 x 10(-8)M) also reduced blood flow in the anterior uvea. The effect was most pronounced in the iris. Neither drug had any appreciable effect on choroidal or retinal blood flow. Both drugs caused pupillary constriction but the reduction in blood flow was not secondary to miosis. The effects on the intraocular pressure and aqueous humor protein concentration were inconsistent. The reduction in blood flow of the anterior uvea after intracameral injection of acetylcholinesterase inhibitors is consistent with a cholinergic vasoconstriction previously described in the eye during electrical stimulation of the oculomotor nerve. PMID- 1506756 TI - Precorneal sampling techniques for ophthalmic gels. AB - Drug-cornea contact time is a critical issue in ocular drug delivery. Existing methods for its experimental determination are developed mainly for eye drops and ointments, and have not been reported for ophthalmic gels. The present study evaluated two tear film sampling techniques (capillary tubes and Schirmer strips) and one recovery technique (cotton swab) for their suitability for the determination of precorneal drug concentration as a function of time for ophthalmic gels. The study was conducted using the rabbit eye model, and the gel studied was a commercial polyacrylate-based gel containing pilocarpine HCl. The three techniques explored yield similar results with respect to drug-cornea contact time, about one hour for the gel studied. The strip method suffers from a gel-carry-over problem at the early time points; therefore it is not recommended for tear sampling until most of the gel is cleared from the cul-de-sac. Successful tear sampling was accomplished using capillary tubes. Drug concentration in the tear film as a function of time determined using this technique reveals not only the duration of contact between the drug and the cornea, but also demonstrates a nonuniform drug distribution in the tear film at the early time points (10 and 30 minutes). Finally the cotton swab technique is gentle, easy, and nondestructive. It recovers total drug remaining in the cul-de sac but does not yield information for the tear film. PMID- 1506757 TI - Absorption, distribution, metabolism, and excretion of bacteria-derived hyaluronic acid in rats and rabbits. AB - The feasibility of using bacteria-derived hyaluronate solution as a viscous aid for anterior chamber surgery was examined by studying the pharmacokinetic behavior and metabolic fate of 14C-labelled material, following administration to rats and rabbits. Intravenously-administered HA disappeared rapidly from the blood of rabbits and rats with a mean t1/2 of 5.3 and 3.7 min, respectively. The labelled material has concomittantly accumulated in the liver, where it was digested to oligomeric sugar subunits; these were further utilized metabolically either for energy generation or for incorporation into new high molecular weight species. Metabolic cage studies has indicated that most of the 14C-HA label administered intravenously to rats was excreted as CO2 via the respiration within 24h, while a smaller portion was excreted in the urine. The disposition of viscous 14C-HA administered into the anterior eye chamber of rabbits was slow and followed first-order kinetics with a t1/2 of 10.5h. No degradation occurred in the aqueous humour. Low blood levels of 14C-labeled material were found during 72h after intra-ocular administration. The results indicate that the absorption, distribution, metabolism and excretion of bacteria-derived HA is similar to those of the currently used ophthalmic surgery HA aids extracted from rooster combs. PMID- 1506758 TI - Review: pathogenesis, progression, and therapeutic intervention of diabetic neuropathy. PMID- 1506759 TI - Duration and long-term efficacy of phenylephrine-induced reduction in the systemic absorption of ophthalmic timolol in rabbits. AB - Co-administration of phenylephrine decreases systemic timolol absorption after a single topical ocular dose of timolol in rabbits. This is probably due to vasoconstriction in the conjunctiva of the eye and nasal mucosa. In this study, we evaluated the duration of action and long-term efficacy of phenylephrine in reducing the systemic absorption of ophthalmic timolol in pigmented rabbits. Although co-administered phenylephrine had a short duration of interaction with systemic timolol absorption (20-60 min), its effect on systemic timolol absorption was substantial. The long-term vasoconstrictive effect of phenylephrine was studied by administering timolol-phenylephrine eyedrops into the eyes of rabbits once a day for two months. Systemic peak concentrations of timolol following timolol-phenylephrine eyedrop administration remained unchanged throughout the study. Phenylephrine may be useful additive in decreasing the systemic concentrations of ophthalmic drugs. PMID- 1506760 TI - Auxiliary tackles catastrophic high school football injuries. PMID- 1506761 TI - LSU Medical Center initiates family medicine clerkship program for third year medical students. AB - This article takes note of the family physician shortage in Louisiana and the continuing need to inform medical students of the career choice in family medicine. Drs English, Gatipon, and Catlin describe the planning stages, the training of clinical teachers, and the implementation of a third (junior) year required clerkship in family medicine at LSU School of Medicine in New Orleans. The students who participated in the pilot year of the program have been enthusiastic about the value of the experience in their total medical education. PMID- 1506762 TI - Nontyphi Salmonella sepsis in an eight-year-old boy. AB - Nontyphi bacteremia is a rare event in older children, especially in those without predisposing conditions. We report a case occurring in a normal 8-year old boy from south Louisiana whose prolonged illness may, in part, have been iatrogenic. Antibiotic treatment is also discussed. PMID- 1506763 TI - ECG of the month. End of the block. Second-degree AV block. PMID- 1506764 TI - Cervical lymph node biopsy. AB - Controversy among head and neck oncologists has centered for many years around the appropriate and inappropriate use of cervical lymph node biopsy. Many authors contend that untimely cervical node biopsy, at best, is unnecessary, and, at worst, may lead to early recurrence and death. More recent data show that adjuvant radiation therapy may ameliorate the adverse effects of lymph node biopsy. At present, although cervical lymph node biopsy is not recommended for the diagnosis of head and neck cancer, it does not appear to shorten survival if appropriate management is administered subsequently. PMID- 1506765 TI - Renal cell carcinoma with extension into the inferior vena cava and the right atrium. PMID- 1506766 TI - "Complete" lumbar hernia. PMID- 1506767 TI - Differences in the onset of the inflammatory response to cutaneous leishmaniasis in resistant and susceptible mice. AB - Sites of cutaneous infection with Leishmania major in genetically susceptible (BALB/c) and resistant (C57B1/6) mice were investigated for the early inflammatory response (6 h to 12 days) by electron microscopy combined with enzyme-histochemical methods. Susceptible BALB/c mice spontaneously recruited only polymorphonuclear leukocytes (PMNs) at the site of infection. Infiltrating mononuclear phagocytes (and eosinophils) were first observed at day 1 in a ratio equal to the influx of PMNs (about 40%). This pattern persisted during the following 11 days of infection. In the resistant C57/B16 mice, the first cellular infiltrate at the infected site contained mononuclear phagocytes (25%) and eosinophils (15%) besides PMNs (60%). Within 3 days after infection, mononuclear phagocytes became the dominant population of cells in cutaneous lesions (up to 80%). It was found in situ that L. major accumulated and replicated in immature macrophages, that is, intermediate stages between monocytes and resident macrophages, which were found in lesions of both strains. The burden of parasites was, however, degraded more rapidly by the infiltrating cells of the resistant mice than by those of the susceptible ones. Within the first 4 days of infection, the parasites were found in PMNs, mononuclear phagocytes, and extracellular spaces in both strains. In susceptible mice this distribution pattern persisted up to 12 days after infection; in resistant C57B1/6 mice parasites accumulated inside mononuclear phagocytes within this period. It is concluded that the features of acute inflammation during leishmaniasis in BALB/c mice are sustained over a prolonged period that is ineffective in the elimination of L. major. PMID- 1506768 TI - Assessment of neutrophil leukocyte secretory response to fMLP in whole blood in vitro. AB - A simple, precise method has been developed for assessing neutrophil secretory responses (release of vitamin B12 binding protein from specific granules) to challenge of aliquots of whole blood with the bacterial chemotactic peptide N formylmethionyl-leucyl-phenylalanine (fMLP). Dose-response studies performed on blood from normal healthy volunteers showed higher maximal secretory responses in males than females (33.3 +/- SEM 2.2 vs. 27.4 +/- 2.5, P less than .005) a left shift in dose-response curves after feeding compared to fasting (P less than .005), spontaneous up-regulation of responses in blood incubated at 37 degrees C for 1 h, and marked upregulation in response to preincubation with endotoxin. This whole blood challenge method may be used to study neutrophil responses in groups of individuals or patients without the confounding effects of changes in cell responses resulting from cell isolation procedures. The method may also be used as a bioassay for neutrophil-activating factors. PMID- 1506769 TI - Effects of phenobarbital on leukocyte activation: membrane potential, actin polymerization, chemotaxis, respiratory burst, cytokine production, and lymphocyte proliferation. AB - Leukocyte activation is known to involve cell membrane potential changes. Phenobarbital, an anesthetic and anticonvulsant that can inhibit neuronal membrane depolarization, may also affect leukocyte activation. Measuring membrane potential, actin polymerization, chemotaxis, superoxide production, lymphocyte proliferation, intracellular calcium concentration, and cytokine production, we found that phenobarbital at a concentration of 15-30 micrograms/ml, which is considered a therapeutic serum level for controlling seizures, did not affect polymorphonuclear neutrophil (PMN) activation. At levels higher than 100 micrograms/ml, phenobarbital significantly suppressed formylmethionyl-leucyl phenylalanine (fMLP)-induced chemotaxis. Concentrations greater than 300 micrograms/ml also inhibited phorbol myristate acetate-stimulated membrane potential change. In contrast, 30 micrograms/ml phenobarbital significantly inhibited lymphocyte proliferation stimulated by phytohemagglutinin (PHA) and pokeweed mitogen. This concentration of phenobarbital also suppressed the increase of intracellular free calcium induced by PHA. However, only a higher concentration of phenobarbital (300 micrograms/ml) was able to inhibit PHA induced interleukin-2 (IL-2) production and suppress the proliferation of PHA induced IL-2 receptor-bearing lymphocytes. These results suggest that concentrations of phenobarbital associated with anticonvulsive levels do not affect PMN activation but suppress lymphocyte activation, possibly by affecting intracellular signal transduction. PMID- 1506770 TI - Impaired stimulus-response coupling in association with increased growth rate of HL60 cells. AB - Impairments in the respiratory burst and stimulus-response coupling were studied with respect to the increased rate of cell replication that occurred in HL60 cells during repetitive passages in cell culture. During a 45-week period of culture, HL60 cells developed a progressive increase in rate of replication. Concomitantly, undifferentiated cells developed an impairment in ATP-induced calcium mobilization. The percentage of cells that could be differentiated with dimethyl sulfoxide progressively diminished. Differentiated cells developed an impairment in both the respiratory burst and secretion of beta-glucuronidase. In addition, regulation of the respiratory burst by cAMP agonists including isoproterenol, adenosine, and prostaglandin E2 was reduced in rapidly proliferating cells. Thus, multiple changes in stimulus-response coupling occur during cell culture in association with an increase in rate of cell replication. It may be important to recognize progressive impairments in cell function in studies using repetitive samples of HL60 cells from a continuously maintained cell population. The observed impairments in stimulus-response coupling may be relevant to unregulated cell growth in neoplastic disease. PMID- 1506771 TI - Effect of lipopolysaccharide on transport and metabolism of arginine in mouse peritoneal macrophages. AB - The transport activity of arginine in mouse peritoneal macrophages was strongly induced when they were cultured with 1 ng/ml bacterial lipopolysaccharide (LPS) for 12 h. Arginine in the medium decreased whereas ornithine in the medium increased during the culture. This time-dependent change of arginine to ornithine was accelerated by LPS. However, the activity of arginase in the macrophages did not change during the culture with or without LPS and release of arginase from the cells to the medium was not detected. It is suggested that the transport of arginine and ornithine was a rate-limiting step in arginine-to-ornithine conversion in the macrophage culture medium. A possible role of the induction of arginine transport activity in the macrophage cytocidal activity due to arginine depletion and nitric oxide production is discussed. PMID- 1506772 TI - Type I interferons (IFN-alpha and -beta) suppress cytotoxin (tumor necrosis factor-alpha and lymphotoxin) production by mitogen-stimulated human peripheral blood mononuclear cell. AB - We studied the effect of the different types of interferons on the production of cytotoxin by human peripheral blood mononuclear cells (PBMCs) stimulated with the mitogen phytohemagglutinin (PHA). Maximum secreted levels of cytotoxin were observed at day 3 in culture and consisted of both tumor necrosis factor alpha (TNF-alpha) and lymphotoxin as determined by specific antibodies. Type I interferons (IFN-alpha and IFN-beta) consistently suppressed cytotoxin production. Both TNF-alpha and lymphotoxin were significantly suppressed. Mean suppression by IFN-alpha and IFN-beta (1000 U/ml) was 56 and 66%, respectively, in PBMCs from 18 different donors. The suppressive effects of IFN-alpha and IFN beta on cytotoxin production were dose responsive over a range of 10 to 1000 U/ml. Type II interferon (IFN-gamma) did not have consistent significant effects. Pretreatment with IFN-alpha or IFN-beta for 24 or 48 h prior to PHA stimulation also resulted in significant suppression. Supplementation with interleukin-2 (10 U/ml) or IFN-gamma (1000 U/ml) did not overcome cytotoxin suppression by IFN alpha or IFN-beta. Cytotoxin suppression by IFN-alpha and IFN-beta together appeared to be noninteractive. Suppression appeared not to be due to blockade of the cytotoxin release, since both cell-associated cytotoxin and secreted cytotoxin were suppressed to the same level. These results demonstrated that cytotoxin and lymphotoxin production by PHA-stimulated PBMCs could be down regulated by type I interferons and that there is a substantial difference between the action of type I interferons and type II interferons (IFN-gamma) in modulating the biosynthesis of cytotoxins. PMID- 1506773 TI - Effects of glucocorticoids on the TPA-induced monocytic differentiation. AB - The human monocytic cell line U937 was used as a model system to investigate the effects of glucocorticoids on monocytic differentiation. Upon incubation with the phorbol ester 12-O-tetradecanoylphorbol-13-acetate (TPA) (5 x 10(-9) M) for 48 to 72 h, the immature U937 cells ceased to proliferate and became morphologically and functionally macrophage-like. Preincubation of the cells with glucocorticoids (dexamethasone and prednisolone, 10(-7) and 10(-6) M) but not progesterone (10( 6) M) had marked effects: The cells remained in suspension and developed very little cell-cell interaction. This correlated with decreased expression of the surface molecules ICAM-1 and CD18 as determined by fluorescence-activated cell sorter analysis. The TPA-induced ability of the cells to release lysozyme or to generate reactive oxygen radicals (determined as reduction of nitroblue tetrazolium) was markedly reduced. The induction of cyclooxygenase activity and thus the ability to release prostanoids was almost completely abolished. Inhibition of prostanoid synthesis was also observed when the glucocorticoids were administered 24 or 48 h after TPA. The primary step of TPA induction, the activation and translocation of protein kinase C, however, was not affected by glucocorticoids as determined by activity measurements and Western blot analysis. There was no change in the subsequent TPA-induced induction of c-fos. The down regulation of the differentiation-related oncogenes c-myc and c-myb was the same in cells treated with TPA in the presence or absence of glucocorticoids. Furthermore, no significant effect of glucocorticoids on the TPA-induced growth arrest was observed. Glucocorticoids thus interfere with TPA-induced functions, which are typical for activated macrophages; however, they do not impair the differentiation process and concomitant growth inhibition. PMID- 1506774 TI - The myeloid leukemia cell line HL-60 produces a factor that induces chloride secretion in cultured epithelial cells. AB - When activated, polymorphonuclear leukocytes (PMNs) produce a small soluble factor, termed neutrophil-derived secretagogue (NDS), that elicits electrogenic Cl- secretion--the transport event responsible for hydration of mucosal surfaces. Work toward purification of this factor has been hampered by variability in activity of PMN-derived NDS. Using a human-derived intestinal epithelial cell line (T84) that serves as a model for studies of the regulation of electrogenic Cl- secretion, we find that the human promyelocytic leukemia cell line HL-60 secrets a factor with NDS-like activity. Buffer conditioned by HL-60 cells (10(7) cells/ml for 1 h), when applied to T84 monolayers grown on permeable supports and analyzed by routine electrophysiological techniques, elicited a short-circuit current (Isc) of 11.7 +/- 1.02 microA/cm2. This short-circuit current was sensitive to bumetanide, an inhibitor of the basolateral Na-K-2Cl cotransporter, and was dependent on the presence of chloride in the assay buffers. Such data indicate that buffer conditioned by HL-60 cells stimulates electrogenic Cl- secretion. Like NDS, the active factor in HL-60-conditioned buffer has a nominal molecular weight of less than 500 and was increased by activation of cells with phorbol ester. 125I and 86Rb efflux assays confirmed that the secretagogue released by stimulated HL-60 cells, similar to PMN-derived NDS, preferentially stimulates opening of Cl- rather than K+ channels in T84 cells. Lastly, release of NDS-like bioactivity increases when HL-60 cells are differentiated toward granulocytes compared to cells differentiated toward monocytes. PMID- 1506775 TI - Fucose-activated killer cells. I. Enhanced TNF-alpha mRNA accumulation and protein production. AB - Our previous studies have shown that the monosaccharide alpha-L-fucose significantly enhances the cytolytic capacity of peripheral blood mononuclear leukocytes (PBMLs). To examine possible mechanisms through which fucose affects cytolytic activity, we studied the production of cytokines after alpha-L-fucose stimulation. In this report, we show that fucose induced a minor but significant augmentation of production of interleukin-2 (IL-2), but anti-IL-2 antibodies did not completely inhibit fucose-activated cytolysis. Fucose induced significantly higher secretion of TNF-alpha by both lymphocytes and monocytes. The nature of the lytic molecule detected in the TNF bioassay was verified with specific neutralizing antibodies. In addition, fucose induced the accumulation of TNF alpha mRNA in a time-dependent manner with a peak at 8 h and a return to baseline values at 20 h after stimulation. In vitro nuclear transcription assays determined that fucose augmented the rate of transcription of the TNF-alpha gene, and inhibition of de novo transcription with actinomycin D indicated that the turnover rate of the TNF-alpha mRNA was not affected by fucose stimulation. We also determined that fucose did not modulate the mRNA expression of the pore forming protein, a major lytic protein involved in lymphocyte cytotoxicity. Specific neutralizing antibodies indicated that TNF-alpha was not an effector molecule in fucose-activated killing of K562 or Raji target cells but that this cytokine had an essential role in the induction of the augmented killing by alpha L-fucose. PMID- 1506776 TI - Interleukin-6 in mouse hypersensitivity pneumonitis: changes in lung free cells following depletion of endogenous IL-6 or direct administration of IL-6. AB - In this study, we examined the role of interleukin-6 (IL-6) in the development of chronic lung inflammatory conditions, using a mouse model of hypersensitivity pneumonitis established by intranasal instillation of the thermophilic actinomycete Faeni rectivirgula. Challenged mice developed an early neutrophilic response at 24 h, followed by a macrophage/lymphocyte recruitment. The impact of IL-6 on the development of the inflammatory response was assessed by giving infusions of a monoclonal antibody against IL-6 so as to deplete endogenous levels of this cytokine or by giving exogenous IL-6 to challenged mice. Mice challenged intranasally with the actinomycete and given the anti-IL-6 antibody developed a strong, sustained neutrophilic response, with a significantly higher lung free cell number than control mice. Assessment of fibrosis by measuring lung hydroxyproline levels showed that challenged mice given anti-IL-6 developed more significant fibrosis than control mice. Conversely, infusions with IL-6 diminished F. rectivirgula-induced cell recruitments and the fibrotic response in the lungs. Moreover, alveolar macrophages from mice given 2 weeks of F. rectivirgula treatment released high levels of tumor necrosis factor alpha (TNF alpha) bioactivity upon in vitro lipopolysaccharide challenge, compared to mice instilled with saline only. This TNF-alpha activity produced by macrophages was decreased by in vivo IL-6 treatment and enhanced by in vivo neutralization with anti-IL-6. These observations suggest that IL-6 may play a role in regulating the cellular recruitment in the lungs during an inflammatory response, with dramatic consequences for the cellular profile in the bronchoalveolar lavage and the subsequent fibrosis. PMID- 1506777 TI - Effects of antiorthostatic suspension and corticosterone on macrophage and spleen cell function. AB - The purpose of this study was to determine whether antiorthostatic suspension of C3HeB/FeJ mice for a period of 11 days affected macrophage and spleen cell function. We found that antiorthostatic suspension did not alter macrophage secretion of prostaglandin E2, tumor necrosis factor alpha, and interleukin-1. Antiorthostatic suspension also did not affect macrophage-mediated contact dependent cytotoxicity, TNF-mediated cytotoxicity, expression of class II histocompatibility molecules, or concanavalin A and Bandeiraea simplicifolia lectin binding sites. The proliferative response of splenic T cells in response to mitogens and staphylococcal exotoxins was significantly enhanced in antiorthostatically suspended mice. We detected significantly higher concentrations of corticosterone in the plasma of antiorthostatically suspended mice. Therefore, there did not appear to be any direct immunosuppressive effects of corticosterone on the parameters tested. PMID- 1506778 TI - Tumor antigen presentation by epidermal antigen-presenting cells in the mouse: modulation by granulocyte-macrophage colony-stimulating factor, tumor necrosis factor alpha, and ultraviolet radiation. AB - I-A+ epidermal antigen-presenting cells (APCs, Langerhans cells) have been shown to present tumor-associated antigens (TAAs) and to induce tumor immunity in vivo. This study examined the effects of ultraviolet radiation (UVR) and the cytokines granulocyte-macrophage colony-stimulating factor (GM-CSF) and tumor necrosis factor alpha (TNF-alpha) on the ability of epidermal cells (ECs) to induce or to elicit immunity against the murine spindle cell tumor S1509a. Naive syngeneic mice were immunized three times at weekly intervals with ECs that had been cultured in GM-CSF for 18 h and then pulsed with TAA derived from S1509a. This resulted in protective immunity against subsequent tumor challenge, providing a model to study the conditions required for sensitization against TAAs by epidermal APCs. Culture of ECs in GM-CSF was required for induction of significant protective tumor immunity, and UV irradiation or incubation in TNF alpha for 2 h after GM-CSF incubation abrogated the immunostimulatory effect of GM-CSF. However, unlike UVR, TNF-alpha did not significantly inhibit the induction of immunity when ECs were exposed to TNF-alpha before overnight incubation in GM-CSF, together with GM-CSF, or after pulsing with TAA, and anti TNF-alpha antibody treatment did not abrogate the effects of UVR on this system. Furthermore, TNF-alpha incubation of ECs augmented their ability to elicit delayed-type hypersensitivity (DTH) and also enhanced elicitation of DTH by GM CSF-cultured ECs, whereas UV-irradiation reduced it in a dose-dependent fashion. Taken together, these results demonstrate that GM-CSF, TNF-alpha, and UVR are significant regulators of tumor antigen presentation by epidermal APCs and that the effects of the cytokines examined differ with regard to induction or elicitation of immunity. PMID- 1506779 TI - Lytic effects of Actinobacillus actinomycetemcomitans leukotoxin on human neutrophil cytoplasts. AB - Actinobacillus actinomycetemcomitans leukotoxin lysed human neutrophil cytoplasts. The reaction was associated with a rapid influx of extracellular calcium, a collapse in membrane potential, release of lactate dehydrogenase, and overt disintegration of the plasma membrane. These functional and structural alterations in the plasmalemma of neutrophil cytoplasts reinforce the hypothesis that A. actinomycetemcomitans leukotoxin acts as a pore-forming, membranolytic agent and indicate that neutrophil cytoplasts are useful tools in studying the biology of membrane-active toxins. PMID- 1506780 TI - Interactions between HIV-infected monocytes and the extracellular matrix: HIV infected monocytes secrete neutral metalloproteases that degrade basement membrane protein matrices. AB - The frequency of human immunodeficiency virus (HIV)-infected monocytes that spread on a model basement membrane was about twofold greater than that of an equal number of uninfected control cells through the initial 12 to 18 h of culture. By 24 h, virtually all HIV-infected and uninfected control cells spread on the basement membrane gel. The frequency of spread cells in the uninfected control population was less than 10% of total cells by 12 days. In contrast, 30 to 40% of HIV-infected monocytes remained spread through this time interval and formed a dense interdigitated network of cell processes on and into the gel matrix. Invasion of the basement membrane matrix by HIV-infected monocytes suggested increased secretion of proteases able to digest the gel. Indeed, levels of neutral protease activity in culture fluids from HIV-infected monocytes were significantly higher than those from equal numbers of uninfected control cells. High levels of protease activity in culture fluids of HIV-infected monocytes required productive virus infection and were not observed with cells exposed to T cell-tropic HIV isolates. The predominant protease activity in these cultures was a 92-kd neutral metallogelatinase. HIV-induced changes in monocyte metalloprotease activity may be important for extravasation of infected cells to tissue or for the development of AIDS-associated neuropathology, carcinogenesis, and opportunistic infection. PMID- 1506781 TI - Of chromosome X and Y--of passion. PMID- 1506782 TI - Male sexual problems and the general physician. PMID- 1506783 TI - Medical evaluation of erectile dysfunction. PMID- 1506784 TI - The sexual difficulties of women. AB - Despite the fact that women are susceptible to experiencing a wide variety of sexual difficulties and complaints during their lifetime, it is also true that women are sexually resilient and are capable of satisfactory sexual response throughout their life cycle. Often, permission and reassurance, coupled with sensible suggestions are sufficient to overcome bothersome sexual difficulties. When this is not helpful, referral to a well-trained sexual or couples' therapist is indicated. PMID- 1506785 TI - Hormones, behavior, and sexuality in women. AB - Many hormones are involved in the control of human sexuality. Clearly both androgens and estrogens are important parts of the picture. The physiologic role of prolactin, thyroid hormones and gonadotropins is not clear. The part played by neurotransmitters can only be guessed at. The neuroendocrine interaction governing female sexuality is far less understood than in the male. For example while there is a loss of tumescence in the vaginal tissue in diabetic females there is no loss of sexual function as in the male. The effects of deletion and addition of sex steroids in the female are far less predictable than in the male. Environmental and psychosocial factors are probably more important in the total picture. The role of hormones in the sexual function and psychological makeup of women is important. The exact role of the endocrine system in their psychosexual function is by no means clear. A great deal of research is required to ratify or disprove many of the speculative assertions found in today's literature. Studies of female sexuality would seem to have acquired a new urgency. Too often attempts at such serious study is met with a snicker and little or no funding is forthcoming. Unfortunately we know more about the sexuality of most animal species than our own. We have to take the study of female sexuality far more seriously to solve these problems. PMID- 1506786 TI - Evaluating couples for sex therapy. PMID- 1506787 TI - Sexual misconduct by physicians. PMID- 1506788 TI - Sexual harassment: it's not just applicable to judges and law professors. PMID- 1506789 TI - Clinical features of systemic lupus erythematosus in Thai males and females. AB - From 1976 through 1988, 726 patients with systemic lupus erythematosus (SLE) were admitted to the Medical Service of Chulalongkorn Hospital, 666 cases (91.7%) being female and 60 cases (8.3%) male (the female-to-male ratio = 11:1). Clinical comparison of 60 males and 130 females (by randomized selection from the total of 666 females) was made. Onset of disease in males occurred later than in females (29.2 +/- 12.2 years vs 25.8 +/- 10.7 years, p less than 0.01). The majority of clinical manifestations were similar; however, musculoskeletal (63.3 vs 73.3%), cardiac manifestations (13.3 vs 26.1%) and Raynaud's phenomenon (18.3 vs 35.4%) were less common in males than females (p less than 0.01), whereas hematologic manifestations were more common in males than females (p less than 0.01). PMID- 1506790 TI - Wilson's disease. AB - Fourteen cases of Wilson's disease in Thais were studied retrospectively. Most were in the second and third decades. The hepatic form occurs in all age groups and the most common presentation was cirrhosis and complications. Neurological complications were observed during the second decade and consisted of Parkinsonism, dystonic and pseudosclerotic forms. A Keyser-Fleisher ring was detected in 2/3 of the cases. D-penicillamine was the mainstay of our therapy. Death in this series was related to crisis such as acute hemolysis, hepatitis as well as septic complications of cirrhosis. Since Wilson's disease is a treatable and preventable disorder, early clinical diagnosis and screening of asymptomatic siblings is mandatory. PMID- 1506791 TI - Double-blind evaluation of enalapril in patients with systolic heart failure. AB - Fifty-six patients with a mean age of 58 years, 14 females and 42 males, all with dominant systolic heart failure (33 in functional class 3 and 4) were randomised to receive either added placebo or added enalapril to their heart failure medication. There were 13 patients in this group who had their trial drug switched after a certain period to allow direct but blind comparison between placebo and enalapril. Cardiac mortality with enalapril was 32 per cent compared to 48 per cent with placebo at intervals after initiating therapy of 20.0 +/- 19.4 versus 14.3 +/- 11.5 months respectively. When compared to a preceding control period, 80 per cent of the enalapril patients improved in contrast to 21 per cent of the placebo. However, when a comparison was made directly between enalapril and placebo, enalapril was better in 31 per cent and placebo was better in 8 per cent of the patients. It is concluded that in certain patients with systolic heart failure from non-valvular and non-hypertensive causes, enalapril is beneficial when added to the conventional treatment. An argument is also presented that to cost-effectively identify the group who will benefit, a short term ACE-I trial after the conventional antifailure therapy can be considered in all patients with systolic heart failure. PMID- 1506792 TI - Pregnancy following transfer of frozen-thawed embryo: a preliminary report. PMID- 1506793 TI - Cholinesterase activity in the chondrocranium of normal and exencephalic mouse fetus with trisomy 12. AB - Cholinesterase (ChE) activity in the chondrocranium of normal and exencephalic trisomy 12 mouse fetuses was studied. Non-specific cholinesterase activity was found strongly in the developing bone cells at the central zone and weakly in the more maturely developed bone cells at the peripheral zone of the chondrocranium of both normal and exencephalic trisomy 12 mouse fetuses. In exencephalic mouse fetuses, the ChE-activity was lesser than in the normal ones which corresponded to hypoplastic chondrocranium. The centrifugal direction of the maturity of individual bone cells could be demonstrated by the activity of cholinesterase. The young bone cells showed strong ChE-activity while the more matured cells showed weak ChE-activity. The enzyme activity disappeared when the definite tissue structure was well developed. From this study, it may be concluded that ChE plays a role in chondrocranium development which is different from its known function in the adult tissue. PMID- 1506794 TI - The correlation between osmolality and specific gravity of parenteral nutrition solution. AB - The correlation between osmolality and specific gravity of parenteral nutrition solutions containing various concentrations of amino acid and glucose were studied. There is good correlation between osmolality and specific gravity up to 1,000 mOsmol/kg H2O and 1.050, respectively. There are strong correlations between osmolality and amino acid concentration at each concentration of glucose. An equation which can be applied for quick calculation of osmolality of the solution from amino acid and glucose concentrations is: Osmolality (mOsmol/kg H2O) = 74.36 G + 163.91 A - 36.56. The results of this study can be adopted by all physicians for quick assessment of the osmolality of the PNS before administration to patients. PMID- 1506795 TI - An investigation into the climacteric in Nigerians. AB - The alterations in the hormonal levels during menopause have been studied in Nigerian women. There was a significant decrease in estradiol level of early menopausal and late menopausal women while the testosterone level increased (P less than 0.01). The luteinizing hormone (LH) and follicle stimulating hormone (FSH) showed significant elevation (P less than 0.01). The elevation of follicle stimulating hormone was about fourteen times higher in early menopausal women and sixteen times higher in late menopausal women when compared to the level in controls. Luteinizing hormone, however, showed an elevation eight times higher in early menopausal women and twelve times higher in late menopausal women. The level of these hormones, the intensity of climacteric symptoms among menopausal Nigerian women and attainable age of menopause was found to be the same as in Caucasians. PMID- 1506797 TI - Febrile and infectious morbidity after abdominal hysterectomy at Srinagarind Hospital. AB - Two hundred and fifty-seven patients who had undergone total abdominal hysterectomy (TAH) in a rural University Hospital in Thailand between September, 1989 and May, 1990 were found to have an incidence of postoperative febrile and infectious morbidity of 35.4 per cent and 10.1 per cent respectively. The risk factors for febrile morbidity are administration of prophylactic antibiotics, a resident being the surgeon and duration of operation time of more than 120 minutes. The risk factors for infectious morbidity included history of previous surgery, performing TAH alone without adnexectomy and omentectomy and also operation time longer than 120 minutes. PMID- 1506796 TI - Post-cesarean section puerperal morbidity. The incidence and risk factors at Srinagarind Hospital. AB - We found that the incidence of post-cesarean puerperal morbidity at Srinagarind Hospital, Khon Kaen University was 5.5 per cent, which is very low compared to other reports. Statistically significant risk factors for post-cesarean puerperal morbidity included having less than 4 antenatal care visits, duration of labour longer than 12 hours and absence of prophylactic antibiotics. PMID- 1506798 TI - Malignant histiocytosis: a chronic variant. AB - An 18-year-old woman had unusual clinical manifestations of malignant histiocytosis (MH) including a long duration of massive splenomegaly, absence of lymphadenopathy, and a number of exacerbations characterized by sudden onset of fever. During life, a definite diagnosis could not be established. The antemortem pathology of the marrow and liver was nonspecific and non-diagnostic. The diagnosis of MH was made after postmortem examination by histologic and immunohistochemical studies. The long duration of massive splenomegaly suggests that this patient could represent a chronic form of MH. PMID- 1506799 TI - Upper urinary tract transitional cell carcinoma in patients with bladder carcinoma. AB - An upper urinary tract tumor following the initial diagnosis of bladder carcinoma is rare. We report 3 patients with bladder carcinoma who later developed upper urinary tract tumors. Ureteral tumor was diagnosed by ureterorenoscope in the first 2 patients, while in the third case, urothelial tumor involving the entire left upper tract was found at the time of planned operation for cystectomy. The etiology, risk factors, and investigation plans were reviewed, in order to make an early detection of tumors. PMID- 1506800 TI - Primary tuberculosis of the nasopharynx. AB - A case of primary tuberculosis of the nasopharynx with cranial nerve 6 and 3 involvement is reported. The disease according to available statistics is very rare. The response to antituberculous therapy was very satisfactory. PMID- 1506801 TI - Morphological estimation of total number of influenza A type virion spikes. AB - When purified and stored influenza A type virions were observed by the negative staining method in electron microscopy, we found disintegrated virions associated with a population of dispersed but clustered spikes. The total spike numbers of the clusters were morphologically counted, and their peak number (about 200) was consistent with the spike number measured by the molecular biology method, described in the other report. PMID- 1506802 TI - An EDTA-KOH method to expose bone cells for scanning electron microscopy. AB - To observe bone cells by scanning electron microscopy (SEM), the mouse parietal bones were processed by decalcification with EDTA and digestion of collagen fibers with KOH to remove the bone matrix, in addition to the conventional preparation for SEM. The critical-point-dried specimens were split into two membranous pieces along the gaps formed by removing the bone matrix. By this method, osteoclasts showing full three-dimensional images of ruffled borders, osteoblasts showing special structures on the surfaces facing the bone matrix, and osteocytes extending many slender processes were clearly demonstrated in SEM. This new method may provide new viewpoints in bone cell biology. PMID- 1506803 TI - The use of t-butyl alcohol in the microdissection of resin corrosion casts for SEM. AB - We developed a new method using t-butyl alcohol in the microdissection of microvascular resin casts of the rat cerebral cortex for scanning electron microscopy. Brains injected with Mercox resin were eroded with sodium hypochlorite solution and dehydrated with graded ethanol. The resin casts obtained were embedded and frozen in t-butyl alcohol at 4 degrees C, and shaved through the planes of interest parallel to the brain surface with a razor blade. The sections were directly freeze-dried and coated with gold and platinum for scanning electron microscopy. Our method enables the demonstration of cross sections of the fine microvascular networks by SEM without any contamination or mechanical artifacts such as distortion and destruction. PMID- 1506804 TI - Quantitative and morphological observations on the ultrastructure of articular tissue generated from free periosteal grafts. AB - This study investigates the ultrastructure of articular tissue generated on osteochondral defects in skeletally immature rabbits from free reversed periosteal allografts after 50 and 100 days of post-operative intermittent active motion. Tissue samples prepared for transmission electron microscopy were compared with normal cartilage and periosteum in terms of cell morphology and the pattern of intercellular collagen deposition. Well-differentiated tissue demonstrated many ultrastructural features of normal articular cartilage while poorly differentiated samples contained cells and intercellular collagen profiles which were somewhat similar to those observed in periosteum. PMID- 1506805 TI - Effects of phalloidin on the epithelial regeneration in the mouse gastric mucosa. AB - Effects of phalloidin on the early (5-60 min) processes of wound repair were examined in the ethanol-injured mouse gastric mucosa. Within 5 min after ethanol was washed out from the stomach, survived epithelial cells changed their shape and became flat extending both lamellipodia and filopodia. The denuded basal lamina was re-covered by these stretched cells within 30 min. When a low dose of phalloidin (5 micrograms) was applied to the wounded stomach, it took 60 min or more to cover the exposed basal lamina. Epithelial cells at the wound edge of the phalloidin-treated stomach often contained unusually thick layer of microfilaments in their subapical region. This observation suggests that phalloidin induces active microfilament assembly mainly in the apical region of epithelial cell processes. PMID- 1506806 TI - Diabetes in Australian aborigines: impact of the western diet and life style. PMID- 1506807 TI - Dexfenfluramine in the treatment of severe obesity: a placebo-controlled investigation of the effects on weight loss, cardiovascular risk factors, food intake and eating behaviour. AB - Dexenfluramine, an effective and safe serotoninergic drug with anorectic and possible food-selection-tuning properties, was investigated in a placebo controlled study of 1 year's duration in severe and refractory obesity. The aim of the study was to assess weight loss, and changes in cardiovascular risk factors, food intake and eating behaviour. Dexfenfluramine- and placebo-treated patients achieved a similar weight loss (greater than 10% of initial weight, by 39.5 and 30.0%, greater than 20% of initial overweight by 42.1% and 32.5% and greater than 10 kg by 41.4 and 33.3%, respectively, of the initial cohorts). Furthermore, the decreases in weight (10.7 vs. 8.0 kg), in body mass index (3.9 vs. 2.9 kg m2) and in waist/hip ratio (0.04 vs. 0.02) were not significantly different. After discontinuation of the drug, the increase in weight (2.8 vs. 1.0 kg) was significantly higher in the dexfenfluramine-treated group. Except for a borderline better effect on glucose of dexfenfluramine, both groups showed similar beneficial changes in food intake and cardiovascular risk factors. Eating behaviour in response to emotional and external stimuli was comparable in the two groups, but placebo-treated patients had to restrain their eating more in order to achieve the same weight loss. Notwithstanding the fact that weight losses and an associated amelioration of health-risk factors were of similar magnitude in dexfenfluramine- and placebo-treated patients, dexfenfluramine might have a useful role in promoting a less stressed adherence to prolonged restriction of energy intake in the severe and refractory obese subject. PMID- 1506809 TI - Drug-induced hepatic injury: an analysis of 1100 cases reported to the Danish Committee on Adverse Drug Reactions between 1978 and 1987. AB - The Danish Committee on Adverse Drug Reactions received 1100 reports of suspected drug-induced hepatic injury during the decade 1978-1987. The causal relationship between drug and hepatic injury was classified as definite in 57 (5.2%) reports, probable in 989 (89.9%) reports, possible in 50 (4.5%) reports and unclassifiable in four (0.4%) reports. Hepatic injuries accounted for 5.9% of all adverse drug reactions reported, and 14.7% of the lethal adverse drug reactions. A total of 47.2% were classified as acute cytotoxic, 16.2% as acute cholestatic and 26.9% as abnormal hepatic function. In 52 (4.7%) cases the hepatic injury was lethal; only 14 (1.3%) cases were chronic. Halothane accounted for 25% of the cases. The incidence of halothane-induced hepatic injury is decreasing, and only one lethal case has been reported since 1981. Next to halothane, sulfasalazine was the drug most often suspected during the last 2 years of the decade. Based on consumption data, the incidence of hepatic injury due to sulindac was estimated to be 18-fold higher than that due to ibuprofen. Paracetamol was reported to induce acute cytotoxic as well as cholestatic reactions in non-alcoholic subjects taking therapeutic doses. PMID- 1506808 TI - Influence of a meat-free diet on the urinary excretion of 3-methylhistidine and creatinine in chronic renal failure. AB - Urinary excretion of 3-methylhistidine has been proposed as an index of internal protein breakdown provided that the intake of exogenous 3-methylhistidine (meat) is excluded. To evaluate the potential use of 3-methylhistidine in the metabolic assessment of patients with advanced renal failure, we studied a group of 11 patients with markedly reduced renal function who were put on a meat-free diet (the protein intake was kept constant). Steady-state plasma concentration and urinary excretion of 3-methylhistidine were not achieved until 14 d after exclusion of meat from the diet. At that time the plasma concentration and urinary excretion of 3-methylhistidine had decreased by 43% and 60%, respectively. We conclude that the delay in reaching steady state makes the clinical use of urinary excretion of 3-methylhistidine in patients with advanced renal failure unpracticable as an index of protein breakdown. The exclusion of meat also resulted in a continuous decrease in the plasma level and urinary excretion of creatinine, with the result that plasma creatinine or its reciprocal become misleading for evaluation of changes in renal function until a new steady state has been reached. PMID- 1506810 TI - Treatment of orthostatic hypotension with sleeping in the head-up tilt position, alone and in combination with fludrocortisone. AB - We studied the effect of sleeping in the head-up tilt (HUT) position, alone and in combination with fludrocortisone, on orthostatic tolerance and blood pressure (BP) in six patients with hypoadrenergic orthostatic hypotension. A high salt diet of 150-200 mmol Na+ d-1 was also administered. Combined treatment reduced orthostatic dizziness in all patients (P less than 0.001), and increased the maximal standing period to at least 10 min. HUT alone (n = 4) reduced the BP decrease after 1 min of standing from -64/-42/-25 +/- 29/21/17 mmHg to -53/-37/ 23 +/- 31/24/20 mmHg (P less than 0.01 for systolic BP). Addition of fludrocortisone to HUT (HUT/fludro) (n = 5) further reduced the BP decrease after 1 min of standing from -63/-40/-24 +/- 20/12/11 mmHg to -21/-19/-8 +/- 12/10/5 mmHg (P less than 0.05 for systolic, mean and diastolic BP, respectively). BP at maximal standing time increased from 58/47/42 +/- 9/8/7 mmHg initially to 95/69/57 +/- 27/22/20 mmHg during combined treatment (P less than 0.05 for systolic and mean BP), and remained unchanged during the 14-month (range 8-70 month) follow-up period. Nocturnal sodium excretion decreased from 8.0 +/- 2.3 mmol h-1 to 5.9 +/- 1.9 mmol h-1 with combined treatment; body weight increased by 1.6 kg on average (range 0.5-2.4 kg) (P less than 0.01). We conclude that the combination of HUT and fludrocortisone effectively minimizes orthostatic symptoms and increases orthostatic BP in patients with hypo-adrenergic orthostatic hypotension. PMID- 1506811 TI - Reproducibility of symptom-limited exercise-stress testing performed 2 and 6 weeks after myocardial infarction. AB - To assess the reproducibility of variables with prognostic value from exercise testing, two symptom-limited treadmill exercise tests were performed in 76 consecutive patients at 2 weeks (predischarge) and 6 weeks after myocardial infarction. In addition, cardiac catheterization was performed at 6 weeks. Exercise duration showed a moderate increase from 7.9 +/- 4.4 min to 8.8 +/- 3.0 min (NS). The rate-pressure product increased from 22,377 +/- 5491 to 24,832 +/- 7261 (P less than 0.001). Reproducibility of ST-segment depression was dependent on the initial response: among the group of 25 patients with ST-segment depression at 2 weeks, only 13 (52%) patients had a reproducible result, whereas among the group of 51 patients without initial ST-segment depression, 40 (78%) patients showed reproducibility. There was no difference in coronary anatomy or ejection fraction between the groups with and without reproducibility results. Among the 30 patients with initial ST-segment elevation, 15 (50%) patients showed reproducibility, while among the 46 patients without initial ST-segment elevation, 42 (91%) patients showed reproducibility: the ejection fraction was significantly higher in the latter group than in the group of patients with lower reproducibility. Thus predischarge exercise testing in postinfarction patients identifies a different group of patients at risk compared to exercise testing after 6 weeks, due to considerable variation between the two tests. PMID- 1506812 TI - A prospective study of the incidence of deep-vein thrombosis within a defined urban population. AB - In a prospective study all positive phlebographies within the well-defined population of the city of Malmo, Sweden, during 1987 were studied in order to determine the incidence of deep venous thrombosis (DVT). Epidemiological data were analysed for the detection of patient groups at increased risk of DVT. The incidence was found to be equal for both sexes, i.e. 1.6 per 1000 inhabitants a year. Risk factors were found to be in accordance with earlier studies. The median age for men was 66 years, compared to 72 years for women. At diagnosis of DVT, 19% of subjects had a known malignancy and within 1 year 5% (19 cases) developed a new malignancy. Of the men, 29% had postoperative or post-traumatic (fracture) DVT, compared to 46% of the women. Fewer patients with DVT than expected (39%) belonged to blood group 0 (31%) (P less than 0.005). Pulmonary embolism (PE) was clinically suspected in only 5% of cases, and diagnosis was verified scintigraphically in 2% of cases. None of these died of PE, but of 6 patients who were found to have PE at autopsy, four died about 4 weeks after the DVT was diagnosed. PMID- 1506813 TI - Normoalbuminuria ensures no reduction of renal function in type 1 (insulin dependent) diabetic patients. AB - Recent reports have suggested that impaired renal function in type 1 diabetic patients may be present despite normal urinary albumin excretion (UAE). We have studied kidney function by means of a constant-infusion technique in normoalbuminuric type 1 diabetic patients without antihypertensive medication (UAE less than 20 micrograms min-1, n = 134), in microalbuminuric patients (20 greater than or equal to UAE less than 200 micrograms min-1, n = 50) and in 27 non-diabetic control subjects. Mean UAE was 4.5 micrograms min-1 (range 1.0-19.3 micrograms min-1) in normoalbuminuric patients, 53.1 micrograms min-1 (range 20.8 147.5 micrograms min-1) in microalbuminuric patients, and 4.0 micrograms min-1 (range 2.1-17.9 micrograms min-1) in controls. Glycosylated haemoglobin A1c was significantly higher in microalbuminuric patients (8.9%, range 5.9-12.6%) than in normoalbuminuric patients (7.9%, range 5.5-11.5%) (P less than 0.0001). Glomerular filtration rate in normoalbuminuric patients (135 ml min-1, range 97 198 ml min-1) was significantly higher than in controls (118 ml min-1, range 94 139 ml min-1) (P less than 1 x 10(-6), and significantly lower than in microalbuminuric patients (142 ml min-1, range 100-186 ml min-1) (P less than 0.05). Mean arterial blood pressure was lower in normoalbuminuric patients (91 mmHg, range 78-108 mmHg) than in microalbuminuric patients (98 mmHg, range 82-131 mmHg) (P less than 1 x 10(-6), but not significantly different from that of controls (89 mmHg, range 73-103 mmHg). We conclude that normal UAE is a reliable indicator of well-preserved renal function. Glomerular hyperfiltration, elevated blood pressure and poor metabolic control are characteristic features of microalbuminuric patients. PMID- 1506814 TI - Syncope in young adults: evidence for a combined medical and psychiatric approach. AB - To determine the principal causes and effects of syncope in young adults, we prospectively evaluated 197 consecutive patients referred to a Syncope Specialty Clinic, comparing young (age 16-39 years, n = 71), middle-aged (age 40-65 years, n = 70) and elderly (greater than age 65 years, n = 56) patients. Psychiatric aetiologies were significantly more common in young patients (39% vs. 20% in middle-aged, and 3.6% in the elderly; P less than 0.001), while cardiac aetiologies were rare in the young (2.8% vs. 12% in the middle-aged, and 16% in the elderly; P less than 0.04). These differences were still significant after controlling for gender. Because psychiatric causes are so common in young patients, we evaluated hyperventilation as a bedside test for syncope patients and found it to have a positive predictive value of 59% for psychiatric causes of syncope. Syncope interfered with daily activities in 62% of young patients, and resulted in anxiety or depression in 70% of the young (no difference when compared with other age groups). Thus syncope in young adults can be a disabling medical condition requiring a unique medical and psychological approach to diagnosis and treatment. PMID- 1506815 TI - Extrinsic allergic alveolitis due to exposure to esparto dust. AB - We here describe the case of a patient with a history of exposure to esparto grass for two and a half years, who presented with clinical symptoms, radiological signs, pulmonary function test and histological findings consistent with the diagnosis of hypersensitivity pneumonitis. Signs and symptoms reappeared after re-exposure. There are few reports of stipatosis in the world literature. PMID- 1506816 TI - Fatal adult Henoch-Schonlein purpura due to small intestinal infarction. AB - A 57-year-old woman presented with classical symptoms of Henoch-Schonlein purpura including arthralgia, abdominal pain, palpable purpuric rash and abnormalities of the urinary sediments. The clinical course was subsequently complicated by severe paralytic ileus leading to respiratory embarrassment. Laparotomy confirmed patchy areas of small bowel infarction due to necrotizing vasculitis. Skin biopsy revealed extensive leukocytoclastic vasculitis with granular deposits of IgA in the blood vessels. Anti-neutrophil cytoplasmic autoantibodies (ANCA) were not detectable. The patient continued to deteriorate despite bowel resection, intensive immunosuppressive therapy and plasma exchange, and eventually died. Gastrointestinal involvement in adult Henoch-Schonlein purpura has previously been reported to have a favourable clinical course. However, our case illustrates the rate but lethal complication of intestinal infarction in patients who fail to respond to conservative treatment. PMID- 1506817 TI - Autoimmune reactions in patients with M-component and peripheral neuropathy. AB - A study of 17 patients with autoimmune axonal or demyelinating peripheral neuropathy in combination with M-component is described. The M-component was associated with MGUS (monoclonal gammopathy of undetermined significance) in 12 patients, CLL in one patient, Waldenstrom's disease in one patient, and myeloma in three patients. Immunohistological examination with direct and indirect fluorescence showed binding of antibodies to nerve structures of the same class and light chain as seen in the M-component. In five cases of IgM M-component, the demyelinating neuropathy was caused by binding of the IgM M-protein and complement C3b to myelin-associated glycoproteins (MAG). In 12 cases with axonal neuropathy, binding of IgG to the connective tissue of the peri- and endoneurium was found in 50% of cases, IgM in five cases, and IgD in one case. None of the patients had central nervous system (CNS) symptoms. The clinical and therapeutic difficulties are discussed; only two patients with an acute course responded to immunosuppression. A marked co-expression of other autoimmune phenomena is interpreted in the light of cross-reactions between the autoantibody and similar tissue autoantigens. PMID- 1506818 TI - Acute myelomonocytic leukaemia with infiltrative peripheral neuropathy. AB - The case of a 71-year-old woman with acute myelomonocytic leukaemia and severe pains in her arms, legs and back during treatment is described. Signs of a generalized polyneuropathy subsequently developed. Autopsy revealed massive leukaemic infiltration of peripheral nerves. Peripheral nerve involvement in acute leukaemia appears to be rare as judged from the very few previously reported cases. The condition should be suspected whenever inexplicable pain problems and signs of peripheral neuropathy occur in patients with acute leukaemia. PMID- 1506819 TI - Life style and genes--the key factors for diabetes and the metabolic syndrome. PMID- 1506820 TI - Neural and behavioral correlates of emotion recognition in children and adults. AB - Event-related potentials (ERPs), accuracy scores, and reaction times were used to examine the recognition of emotional expressions. Adults and 7-year-old children saw upright and inverted chromatic slides of the facial expressions of happiness, fear, surprise, and anger, and were asked to press a button for either "happy" or "angry" faces. A positive-going waveform (P300) was apparent at parietal scalp (Pz) and at left and right temporal scalp. Although the behavioral data were similar for both children and adults (e.g., both had more difficulty recognizing angry expressions than happy ones, and angry expressions were more difficult to recognize upside-down than were happy faces), the ERPs indicated that children responded differently than adults did to happy and angry expressions. Adults showed greater P300 amplitude to happy faces, while children showed greater P300 amplitude to angry faces. In addition, for adults, but not children, there were greater P300 amplitude responses at right vs. left temporal scalp. PMID- 1506821 TI - The effect of object alignment on the representation of depth in young children's drawings. AB - Light and Humphreys (1981, Journal of Experimental Child Psychology, 31, 521-530) provided evidence that young children's drawings, despite infrequently showing view-specific occlusion, do systematically reflect spatial relations within an array. The present research tested the hypothesis that young children's preferences for canonical "best views" interact with array-faithful tendencies to increase early uses of occlusion. Forty-three children between 4 and 7 years of age drew arrays like Light and Humphreys' end-to-end alignments, with end-on views of objects in depth, and arrays aligned side-to-side, with canonical side views of objects in depth. Significantly fewer single-object, view-specific occlusions were produced for end-to-end than for side-to-side alignments. Nevertheless, the former reveal that more children are able to use the vertical dimension to depict multiple objects in depth. Other comparisons suggest an interaction in multiple-object depictions of canonicality with spatial dimension and graphic complexity. PMID- 1506822 TI - The perception of identity by 6 1/2-month-old infants. AB - In Study 1, sixteen 6 1/2-month-olds were habituated to a Reversible stimulus (an upright face that could be perceived as an entirely different upright face when it was rotated 180 degrees) and to a Nonreversible stimulus (a face that could be perceived as upright in only one orientation). Following habituation for each type of stimulus, test trials paired the habituated face with a novel stimulus (an inversion of the same face). For both Reversible and Nonreversible stimuli, the physical difference between the old and new test stimuli was the same (a 180 degrees rotation); however, infants devoted more visual attention to the 180 degrees rotation only when it was a Reversible face, suggesting that the identity change was detected. Experiment 2 ruled out the explanation that infants might have failed to dishabituate to the inversion of the Nonreversible stimulus because they could not remember it. Results are interpreted as evidence that 6 1/2-month-old infants are not limited to face recognition based on similarity in pattern arrangement alone, but are capable of processing faces at a representational level. PMID- 1506823 TI - Asphyxial deaths from the recreational use of nitrous oxide. AB - The recreational use of nitrous oxide is widespread. Nitrous oxide for recreational use is usually obtained from anesthesia tanks or whipped-cream machine chargers or cans. Twenty previously described deaths associated with recreational nitrous-oxide use describe anesthesia tanks and whipped-cream machine dispensors as a source. Five deaths associated with nitrous oxide use are presented; two involving whipped-cream cannisters as the source, two involving anesthesia tanks, and one involving a racing fuel tank as a source of nitrous oxide. Autopsy findings in our cases were subtle or negative, but usually suggestive of asphyxia. Through a laboratory simulation, we have confirmed that nitrous oxide displaces oxygen in a closed space, which probably leads to asphyxia. A review of the literature, neuropharmacology, and pathophysiology of nitrous oxide use is also presented. PMID- 1506824 TI - Electrocution: a review of 155 cases with emphasis on human factors. AB - A review of 155 cases of electrocution were investigated to determine the role of human factors, such as carelessness and intoxication, as contributions. The cases were retrieved by computer coding from the repository of the Armed Forces Institute of Pathology, covering the period 1955-1988. The cases are predominantly of military origin. Cases were divided into low-voltage electrocution (N = 47), high-voltage electrocution (N = 79), lightning strikes (N = 16), and unclassified (N = 13). For each group, data is presented on the circumstances of the incident and the pathologic findings. Blatant carelessness, misuse or improper maintenance of equipment, and intoxication are analyzed as contributory factors. PMID- 1506825 TI - Fungal tunneling of hair from a buried body. AB - Tunnels produced in human head hair by fungal hyphae were examined with a light microscope and with a scanning electron microscope. The tunnels had small diameters and exhibited minimal branching. The use of a backscattered electron detector facilitated the locating of the openings of the tunnels in the surfaces of the hairs. In the backscattered electron image, tunnel openings appeared as dark spots. The tunneling hyphae did not show a preference for a particular location for entering the shaft of the hair. Some hyphae penetrated under the free edges of the cuticular scales, while others burrowed through the surfaces of the scales. PMID- 1506826 TI - A microscopic comparison of fresh and burned bone. AB - Examination of the microstructure of human bone is useful in estimating age at death in forensic science cases. This technique has been tested and is well accepted, however samples of burned bone may complicate analysis because of possible changes in the microstructure occurring during the burning process. In a comparison of fresh and burned ground thin sections taken from midshaft femorae of eight dissecting-room cadavers of known age and sex, this study finds significant shrinkage of microstructural elements through the burning process. These results are compared to previous work on the subject, which found the microstructural elements to increase through the burning process. PMID- 1506827 TI - Estimation of age from a tooth by means of racemization of an amino acid, especially aspartic acid--comparison of enamel and dentin. AB - In a study of age estimation from teeth by means of measuring racemization of aspartic acid (Asp), a representative amino acid, the accuracy of data from enamel and dentin in the same tooth was compared. The correlation of D/L ratio of aspartic acid with actual age gave the following parameters: r = 0.928, sigma = +/- 5.2, k = 4.47 x 10(-4) yr-1 in enamel and r = 0.995, sigma = +/- 1.4, k = 5.75 x 10(-4) yr-1. The difference in ages between one estimated by the D/L ratio and the actual one was within +/- 3 years in dentin, while in enamel an error of from 2 to 11 years was observed. Reaction rate constants of the racemization in a dry postmortem state (15 degrees C) were calculated as k = 9.70 x 10(-8) yr-1 in enamel, and k = 1.33 x 10(-7) yr-1 in dentin. Compared to rates determined from teeth recently extracted from living subjects, the rate was higher in dentin than in enamel. These data reconfirmed that dentin is superior to enamel in making exact age estimations from teeth. PMID- 1506828 TI - Sex determination in subadults using auricular surface morphology: a forensic science perspective. AB - The determination of sex in subadult skeletons remains a problem for several areas of biological anthropology. To date, univariate and multivariate assessments of sex in the young using adult indicators have failed to produce reliable results. However, research in this area continues. In 1980, Weaver proposed a modification of adult differences in auricular surface morphology as an effective means for sex determination in subadult remains. His method was indirectly evaluated by Hunt through a comparison of the sex ratios produced by this technique and the expected 1:1 ratio. The present investigation expands upon both studies by using a sample of subadults of known sex, and by evaluating Weaver's method from two perspectives: 1) what percentage of individuals can be correctly sexed using Weaver's criteria? and 2) what is the probability that an individual case will be correctly sexed based on the presence or absence of auricular surface elevation? The first is of interest to those reconstructing population patterns, while the second is critical to the forensic investigator faced with the diagnosis of an individual case. The sample used in this study consisted of 58 ilia from subadults of known sex ranging in age from birth through 18. In each case, sufficient soft tissues were present to allow absolute sex diagnosis. Each ilium was subjected to a blind examination using Weaver's criteria for auricular surface elevation. Weaver's technique proved most effective on the males in our sample, with an overall accuracy of 85.3%; however, accuracy in sexing females was only slightly better than chance at 58.3%. Our results corresponded closely to Weaver's own values of 85.4 and 57.7% respectively.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1506829 TI - Can we believe what we see, if we see what we believe?--expert disagreement. AB - Forensic experts often disagree. The possible sources of such disagreements are analyzed and possible avenues of resolution indicated. The logic of interpreting scenes, and pattern injuries such as bitemarks, is explained to locate potential sources for interpretive error, and to recommend strategies to avoid compounding such errors when preparing cases. In one sense, two observers may not see the same thing, although their eyesight is normal and they are aware of the same artifact. Cases show that both practical and theoretical investigative expectations affect what count as observations. These expectations confer evidential status on the artifact. When two observers' expectations conflict, they do not see the same thing, so are not presented with the same evidence. Expectations can be either appropriate or inappropriate. These senses are clearly distinguished using illustrative cases. When inappropriate, they cause observational errors of a unique sort supplying one source for disagreement. When inferences are made from these inappropriately sanctioned observations,interpretive errors are compounded and resolutions of disagreement become difficult. These observational and inferential errors are explained, described, and illustrated with cases, along with recommendations for recognizing and avoiding them. PMID- 1506830 TI - Creatinine analysis in single collection urine specimens. AB - Controlled and uncontrolled fluid intake studies were conducted on series of volunteers over the 6 or 12 h of the study periods. Urine specimens were obtained from each subject randomly or at specified times relative to fluid ingestion. Creatinine analysis performed by a modification of the Abbott TDx procedure demonstrates that the values obtained from single collection specimens fall almost in the same range as the values from 24 h pooled collection specimens. The creatinine concentration can be used to indicate possible adulteration of urine specimens by dilution as a means of avoiding detection of use of drugs of abuse. Between 4 and 7 h are required for a decrease in creatinine concentration to about 100 mg/dL from an initial mean of about 170 mg/dL. A minimum of 6 h is needed for any creatinine value to fall to 50 mg/dL or less. Thus, it appears that creatinine output is sensitive to the amount of fluid ingested, but the relationship is neither linear nor immediate. The absence of a significant creatinine concentration in a specimen can be used as an indication of direct or indirect adulteration of the urine specimen by dilution or replacement with water. At NDSL-Great Lakes, a decline of the creatinine concentration to 30 mg/dL is used as a cutoff for differentiating between urine specimens that might have been tampered with to avoid detection of drug use and those specimens that are dilute for other reasons. Values at 10 mg/dL or less are suggestive of replacement by water. The information is provided to local commands for investigation prior to initiation of punitive action by the command. PMID- 1506832 TI - Acute arsenic intoxication: forensic and toxicologic aspects (an observation). AB - The authors report on an acute suicidal arsenic intoxication (di-arsenic trioxide). Death can occur one week after ingestion, despite intensive care. The forensic, anatomopathological and toxicologic aspects are reported. Forty titrations are realized at the level of the biologic fluid in viscera, by absorption spectrophotometry. These data are compared with those in standing literature, especially with the rates determined in normal subjects, following simple environmental impregnation. PMID- 1506831 TI - Poppy seed ingestion: the Oregon perspective. AB - Numerous articles have been published regarding the positive morphine and codeine urinalysis results from the ingestion of poppy seeds. Oregon's perspective towards ingestion of controlled substances focuses around driving under impaired conditions. To determine the influence of the residual opium on poppy seeds to impairment, seven volunteers each ingested 25 grams of poppy seeds baked into bundt cakes. Urine samples were screened by EMIT using 300 ng/ml cutoff levels. All of the urine specimens were found to be opiate positive shortly after consuming the cake; however, after administering a series of standardized drug recognition evaluation tests, no subjects were found to exhibit symptoms of opiate impairment. PMID- 1506833 TI - Distinctive blunt force injuries caused by a crescent wrench. AB - Prompt recognition of patterned injuries by the forensic pathologist can greatly facilitate the investigation and resolution of injury and death cases. Careful observation and description of injuries may provide identification of an assault or murder weapon and contribute to the reconstruction of circumstances of injury. The two cases herein described manifest unusual and distinctive injuries resulting from multiple impacts by adjustable crescent wrenches. Detailed photographs and descriptions of these injuries are provided. PMID- 1506834 TI - Insect larvae used to detect cocaine poisoning in a decomposed body. AB - Insect larvae are often found on human remains long after disappearance of the usual toxicologic specimens. It is important for forensic pathologists and toxicologists to recognize the potential of this unique specimen when routine specimens are not available. Cocaine and benzoylecgonine was extracted from Calliphorid larvae found on a badly decomposed body of a man who had been missing 5 months and was also identified in the decomposing skeletal muscle. This toxicologic information combined with the autopsy findings and the circumstances of the death and disappearance was essential in the determination of cocaine poisoning as the cause of death. PMID- 1506835 TI - A fatality due to propofol poisoning. AB - This report describes a suicide by self-administration of propofol in a 29-year old female radiographer. This is the first published report of death by overdosage with propofol. Propofol was detected in tissues using high performance liquid chromatography. Post mortem femoral blood and liver concentrations of propofol were 0.22 mg/L and 1.4 mg/kg, respectively. The scene suggested that a dose of 400 mg was used. PMID- 1506836 TI - Using pacemakers to identify decedents. PMID- 1506837 TI - Discussion of "Effects of the taser in fatalities involving police confrontation". PMID- 1506838 TI - Occupational exposure to cocaine involving crime lab personnel. AB - The possibility of exposure to cocaine as a result of analyzing it or handling material contaminated by it has been a major concern of laboratory personnel. Several different work environments and simulated situations were examined to assess the likelihood of this type of exposure occurring. Urine specimens were collected and evaluated for cocaine and benzoylecgonine using the Syva ETS System (EMIT). Each specimen was analyzed for the two substances using gas chromatography/mass spectrometry (GC/MS). Urine specimens of laboratory management personnel not working with drug samples showed no trace of cocaine or benzoylecgonine. A urinary benzoylecgonine level of 227 ng/mL was found in the specimen from one narcotics criminalist who was working on a routine case of 2 kilos of cocaine hydrochloride in the Narcotics Laboratory. A maximal urinary benzoylecgonine concentration of 1570 ng/mL was determined in the urine specimen from one narcotics criminalist who was sampling a case containing 50 kilos of cocaine hydrochloride over a period of 3 h. Decreasing the levels of airborne cocaine dust appears to minimize the amount of cocaine absorbed by the criminalists. Gloves, face masks, and goggles prove to be effective in minimizing exposure. PMID- 1506839 TI - Impact of tropical conditions on thin layer chromatography in analytical toxicology: high temperatures and moderate humidities. AB - The impact of high temperatures (24 to 39 degrees C) and low to moderately high humidities (20 to 70%) on the applicability of TLC systems for drug identification was studied during a 6 month climatologic cycle in Burkina Faso (West Africa). In general, the Rf values as observed on the plates were found to be substantially affected as compared with values obtained at temperate climates. Some TLC systems were more affected than others and the largest deviations of up to 30 Rf units were at low humidities. Tropical conditions also had a negative effect on the reproducibility of Rf values. However, when an Rf-correction procedure was applied, using reference mixtures of known drugs on each plate, accuracy as well as reproducibility of the resulting Rfc values were drastically improved and data thus corrected were found to be compatible with existing TLC data bases developed under moderate climatological conditions. The impact of high to extremely high humidities (70 to 100%) remains to be investigated. PMID- 1506840 TI - The distribution of ethanol in postmortem blood specimens. AB - Ethanol was determined by gas chromatography in a variety of tissues and body fluids secured at autopsy in 61 cases. The specimens tested included right and left heart blood, femoral blood, pericardial fluid, cerebrospinal fluid, vitreous humor, urine, stomach contents, and brain. Statistical analysis of the cases revealed no significant differences among the various blood sites tested. However, the variations in blood ethanol concentrations among the various sampling sites within each case were as follows: 40 cases showed differences of less than 25%; 16 cases revealed variability between 25% and 50%, 4 cases had differences exceeding 50%. In one case, satisfactory blood analyses could not be accomplished. The larger variances occurred especially in those instances in which stomach alcohol concentration was 0.50% or greater. In one case, the variability amongst the different blood sites exceeded 400% (femoral blood- 0.043%, right atrium--0.070%, root of aorta--0.156%); the brain was 0.050%, and the stomach contents was 1.2%. For all 61 cases, variances in blood alcohol content among the different sampling sites in a single cadaver ranged from 1.8 to 428%. PMID- 1506841 TI - The effect of dentures and denture adhesives on mouth alcohol retention. AB - A total of 24 alcohol-free, denture-wearing subjects were tested for mouth alcohol retention times with an Intoxilyzer 5000. The subjects were given 30 mL doses of 80 proof brandy to swish in their mouths without swallowing for 2 min prior to expectorating the dose. Subjects were tested under three conditions: 1) with dentures removed, 2) with dentures held loosely in place without an adhesive, and 3) with dentures plus an adhesive. Beyond 20 min following expectoration, mouth alcohol made no significant contribution to the apparent breath alcohol concentration (BrAC), with trace (less than or equal to 0.01 g/210 L) readings found in only two of the subjects. Denture use, both with and without the concurrent use of adhesives does not significantly affect BrAC as long as a pretest alcohol deprivation period of 20 min is observed. PMID- 1506842 TI - Time-course of sensitivity changes as attention shifts to an unpredictable location. AB - Shifting visual attention is often described as analogous to a spotlight moving through empty space between locations. In the present experiment, a peripheral precue summoned attention to an initial location, and 200 ms later a second peripheral cue appeared beside one of two possible second locations, each 14 degrees away from the initial location. The target was twice as likely to appear at the location that had been indicated by the immediately preceding cue as at the location that had been previously cued or that would be cued. Fine-grained temporal analyses indicated that, as attention was shifted, sensitivity to information at the second location gradually increased while sensitivity at the first location simultaneously decreased. Average sensitivity over the two locations during the shift remained significantly greater than average sensitivity immediately following the initial precue. In contrast, an attentional "spotlight" moving from the first to the second location would produce a decrease in average sensitivity to its initial level while the spotlight was between locations. PMID- 1506843 TI - Changing-loudness aftereffect following simulated movement: implications for channel hypotheses concerning sound level change and movement. AB - Listening to a tone changing unidirectionally in sound level causes an illusion of changing loudness in a steady tone afterward. This aftereffect may indicate channels for detecting the feature of change in sound level, which would primarily concern dynamic sound localization. Three subjects, one of whom was the author, participated in this study. The author predicted that opposite adaptation of the ears (the adapting stimulus is heard to move from one ear to the other) should lead to a movement aftereffect. This was not reported by the subjects. However, the subjects did report a changing-loudness aftereffect in a monaural test stimulus, and the characteristics of the changing-loudness aftereffect (such as its magnitude) were consistent with previous data, suggesting a two-stage channel hypothesis: Output from channels for several features, including sound level change, simultaneously stimulate movement channels. PMID- 1506844 TI - Repression-sensitization differences in recovery from learned helplessness. AB - The performance of repressors and sensitizers on a solvable anagram task was assessed after either a short delay (0 to 30 min) or a long delay (2 to 6 hr) following a standard learned helplessness induction. Results indicated that all subjects exposed to the learned helplessness induction exhibited performance deficits, compared with control subjects exposed to no induction. Furthermore, subjects who were tested after the short delay did not perform as well as subjects tested after a long delay. No difference in overall anagram performance was found between repressors and sensitizers. Consistent with theoretical predictions, however, the anagram performance of repressor subjects was significantly better in the long-delay than in the short-delay condition; this significant recovery effect between short- and long-delay conditions was not obtained for sensitizer subjects. Possible theoretical mechanisms for these effects and implications for future research are noted. PMID- 1506845 TI - Can reading ability be measured with tests of memory and processing speed? AB - The author investigated the possibility of estimating reading ability using tests of memory and processing speed that have significantly reduced reading requirements. Four hundred three air force trainees were given tests of their working memory and long-term memory processes, as well as a standardized reading test. A multiple correlation of .79 indicated that global reading ability is substantially correlated with memory processes. Additional analyses indicated that word knowledge and comprehension, the two major components of reading ability, were both explained by the same set of memory process factors, namely, long-term memory processes, semantic memory retrieval speed, and working memory capacity. These results, which are consistent with the view that memory ability underlies reading ability, support the endeavor of measuring reading ability with memory and processing speed tasks. PMID- 1506846 TI - Quantitative information presentation and gender: an interaction effect. AB - The authors investigated whether performance on mathematical test items would be influenced by an interaction between presentation format and gender. One hundred fourteen students in a management accounting course were randomly assigned either to a tabular format or to a graphics format. There were significant main effects for gender and presentation format; men outperformed women, and the subjects who received the tabular format outperformed the subjects who received the graphics format. A significant interaction supported the existence of a conditional relationship between performance on mathematical test items and presentation format. This relationship varied as a function of gender (symmetry permits the interchange of presentation format and gender). Simple effects for the interaction determined that the women who received the graphics presentation did not perform as well as their male counterparts, or as well as other women and men who received the tabular format. The results of this study indicate that presentation format is an important consideration in gender differences for mathematics performance. PMID- 1506847 TI - Effects of reinforcement schedules on rats' choice behavior in extinction. AB - The effects of reinforcement schedules on rats' choice behavior in extinction were studied. In a free-operant chamber equipped with two retractable bars, the experimental animals were trained to press the bars separately for a food reward. One bar delivered the reward on a continuous reinforcement (CRF) schedule, and the other delivered the reward on a partial reinforcement (PRF) schedule. Control animals earned the reward from both bars with the same reinforcement schedule, either a CRF or a PRF. When both bars were simultaneously available during extinction, the experimental animals responded more frequently to the CRF than to the PRF alternative, demonstrating a reversed within-subjects partial reinforcement extinction effect (PREE). A conventional between-subjects PREE was replicated in the control subjects. The results of this study were inconsistent with both Amsel's (1962, 1967) frustration hypothesis and Capaldi's (1966, 1967) sequential hypotheses. PMID- 1506848 TI - White matter lesions in the elderly. AB - The advent of neuroimaging has brought medical attention to the frequency of unsuspected white matter lesions in the brains of elderly people. In 1987 Hachinski suggested the term "leuko-araiosis" to identify such white matter abnormalities detected by computed tomography and magnetic resonance imaging to emphasize that their etiology and clinical relevance require clarification. Since then, leuko-araiosis has been recognized among approximately ten percent of apparently normal, elderly people over age sixty-five. The severity and frequency of leuko-araiosis increases with advancing age, risk factors for stroke, history of strokes particularly of the lacunar type and dementia of both the vascular and Alzheimer type. Current concepts concerning the pathogenesis and neurological concomitants of leuko-araiosis are reviewed. The etiology of leuko-araiosis may be heterogeneous but is most likely ischemic in nature. However, as white matter lesions progress among the elderly they are likely to become associated with cognitive impairments and motor dyspraxias presumably resulting from cortico subcortical disconnections, particularly involving the frontal cortex and basal ganglia and may themselves be considered a radiological "risk factor" or precursor for dementia. PMID- 1506849 TI - Development of myelinated and unmyelinated fibers of human vagus nerve during the first year of life. AB - As an important component of cardiorespiratory control, the vagus nerve and its maturation were evaluated in normal infants in order to provide standards of comparison with infants with dysfunctional neural control mechanisms. Myelinated and unmyelinated fibers in the cervical vagus nerve were examined in 27 term infants. Number of fibers, axon diameters, and myelin thickness were compared among four age groups. The histograms of axon size exhibited a skewed distribution that persisted during the age range examined for both myelinated and unmyelinated vagus fibers. Fiber size distributions of myelinated fibers, however, already showed an incipient multimodal distribution after 3 months. No major increase was observed in the average axon size of myelinated and unmyelinated fibers. A significant increase was observed, however, in the average content of myelin in myelinated fibers expressed as myelin thickness, number of lamellae or g ratio (internal/external diameter). These results suggest an active myelination during the first 9 months of life without a major change in the axonal characteristics of the fibers. A marginal increase in the density of myelinated fibers with age, both in terms of total number and the relation to unmyelinated fibers, suggests a slow transition from unmyelinated to myelinated fibers during the first year of life, particularly during the first 3 months. The present morphometric parameters indicate an active deposition of myelin before the maturation of cross-axonal dimensions. The distribution of g ratios also suggests that optimal conduction velocity is compromised only in a fraction of all vagal myelinated fibers. PMID- 1506850 TI - Increase in diameter of the axonal initial segment is an early change in amyotrophic lateral sclerosis. AB - We measured the diameter of the most distal portion of the axonal initial segment, the neuronal size of anterior horn cells, and the length of the axon hillock plus the initial segment (AH+IS) in the lumbar spinal cord in motor neuron disease. Three patients with amyotrophic lateral sclerosis (ALS) and one with lower motor neuron disease (LMND) were compared with 11 controls. Serial plastic sections stained with toluidine blue and electron micrographs were studied. A total of 214 axons directly emanating from the somata (n = 207) and the primary dendrites (n = 7) were observed in the patients. Approximately 19% of the proximal myelinated axons (24 axons out of 155 in ALS, and 17 axons out of 59 in LMND) were swollen at the first internode, and most of the swellings extended to the middle portion of the initial segment. Electron microscopy showed that the swellings of the proximal axons (the initial segment and the first internode) directly connected with their somata consisted mainly of accumulations of 10-nm neurofilaments. The average diameter of the most distal initial segment was markedly larger in ALS (n = 155) (P less than 0.0001) and LMND (n = 59) (P less than 0.0001) than in the controls (n = 258). Moreover, the average diameter of the most distal portion of even normal-appearing initial segments of the non swollen axons was larger in ALS (n = 131) (P less than 0.0001) than in the controls. The perikarya and axon hillocks connected with the normal-appearing and swollen proximal axons and their dendrites almost always appeared normal.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1506851 TI - Hereditary motor and sensory neuropathy with deafness, mental retardation and absence of large myelinated fibers. AB - Two brothers with a presumably hereditary motor and sensory polyneuropathy (HMSN), sensory-neural hearing loss and mental retardation had clinical features and neuropathological changes in the sural nerve which may set the disorder apart from previously described types of HMSN. Consecutive sural nerve biopsies from one case showed absence of large myelinated fibers and a normal complement of small fibers. We infer from our findings that a developmental abnormality with faulty growth and subsequent axonal atrophy may be responsible. PMID- 1506852 TI - Maximal and minimal motor nerve conduction velocities determined by a collision method: correlation with axonal conduction velocity of type-identified motor units. AB - Maximal and minimal motor nerve conduction velocities of the medial gastrocnemius (MG) muscle nerve were measured by a new collision method in 20 rats of 8-9 weeks of age; the rate of tension increase produced by the muscle was also recorded. Single motor unit analysis in the other 20 rats obtained axonal conduction velocity and contractile properties of type-identified MG motor units. Comparison of the data from these experiments revealed that the maximal and minimal motor nerve conduction velocities obtained by this collision method were most likely to be the axonal conduction velocity of fast-twitch and slow-twitch motor units, respectively. Therefore, these motor nerve conduction velocities in man may also be used as functional parameters of human fast-twitch and slow-twitch motor units, respectively. PMID- 1506853 TI - Inositol 1,4,5-trisphosphate metabolism in the cerebella of Lurcher mutant mice and patients with olivopontocerebellar atrophy. AB - We have investigated inositol 1,4,5-trisphosphate (InsP3) metabolism in cerebellar membranes of normal humans and patients with dominant ataxia ('C' kindred), and also in cerebellar microsomes of Lurcher mutant mouse (a suggested model for cerebellar ataxia). Various [3H]InsP3 metabolites formed were separated by HPLC using 3 successive convex gradients of 1.7 M ammonium formate, pH 3.7. [3H]InsP3 metabolism was rapid and in 15- and 45-day-old control mice cerebella about 50% of [3H]InsP3 was metabolized within 20 s. In 15-day-old Lurcher mice the rate of [3H]InsP3 metabolism was significantly low (40% of normal). [3H]InsP3 metabolism was almost absent in 45-day-old Lurcher mice cerebellar microsomes. The decreased [3H]InsP3 metabolism was consistent with decreased recovery of the various inositol polyphosphates formed. Similarly, in cerebellar membranes of human patients with olivopontocerebellar atrophy (OPCA) a significant decrease in [3H]InsP3 metabolism was observed when compared with normal controls. These data suggest that altered phosphoinositide turnover may be associated with the onset of neuronal degeneration in human OPCA. PMID- 1506854 TI - Dystrophin deficiency causes lethal muscle hypertrophy in cats. AB - Two 5-month-old male Domestic Shorthair littermates showed general skeletal muscle hypertrophy, multifocal submucosal lingual calcification with lingual enlargement, and excessive salivation. Both cats had a reduced level of activity, walked with a stiff gait, and tended to "bunny hop" when they ran. These clinical features were similar to those of previously reported dystrophin-deficient cats. Using multiple dystrophin antibodies, we found that the cats described in this report also showed marked dystrophin deficiency. The histopathology was remarkable for hypertrophy and splitting of fibers, and progressive accumulation of calcium deposits within the muscle. There was little or no endomysial fibrosis at 2 years of age. The natural history of dystrophin-deficiency in cats has not been described: both previous cats had been euthanized at 2 years of age prior to experiencing any life-threatening problems. At 6 months of age, one of the new cats developed megaesophagus because of severe progressive hypertrophy of the diaphragmatic muscles. The diaphragm completely occluded the esophagus, and the cat was euthanized for humane reasons. The second cat remained in good condition until age 18 months when it developed acute renal failure attributed to severe prolonged dehydration and hyperosmolality. The cat recovered after receiving supportive treatment but was unable to maintain fluid homeostasis. The insufficient water intake was attributed to glossal hypertrophy and dysfunction. At age 2 years, the cat received regular subcutaneous injections of low-sodium fluids to maintain proper hydration. The clinical consequence of dystrophin deficiency in cats is lethal muscle hypertrophy. We have called the feline disease "hypertrophic feline muscular dystrophy" (HFMD). PMID- 1506855 TI - Increased leakage of calcium ion from the sarcoplasmic reticulum of the mdx mouse. AB - Using a single skinned muscle fiber, the function of the contractile system and the sarcoplasmic reticulum (SR) were analyzed in the skeletal muscle of the mdx mouse. Activation of the contractile system by calcium ion and the maximum force generation was normal. Ca2+ uptake of the SR was normal as well as regulation of the Ca-induced Ca release (CICR) by Ca2+. However, contracture by caffeine was more prominent in mdx than in control mice. Ca2+ leaked more from the SR of mdx in the presence of EGTA and ATP or its analogue. These abnormalities are probably interrelated; increased leakage of Ca2+ might cause the enhanced response to caffeine, since Ca2+ itself facilitates Ca release by caffeine. The abnormal leakage of Ca2+ might also activate the Ca pump of SR in the resting state, which consume extra ATP and disturb energy metabolism. PMID- 1506856 TI - Delayed expression of dystrophin on regenerating muscle from two siblings with Becker muscular dystrophy. AB - We present here a unique expression of dystrophin on biopsied muscle from 2 siblings with Becker muscular dystrophy (BMD). They had neither muscle weakness nor atrophy. Clustered dystrophin-deficient fibers were constituted to regenerating basophilic fibers (mainly type 2C fiber) based on histochemical stainings. We speculate that the developmental delay in the expression of dystrophin is a characteristic finding in regenerating fibers from asymptomatic and young BMD patients, such as the siblings in this report. PMID- 1506857 TI - Production of soluble autocrine inhibitory factors by human glioma cell lines. AB - Gliomas in vitro exhibit density-limited growth upon the attainment of confluency, an effect usually attributed to cell-cell contact inhibition. Since gliomas have been demonstrated to secrete an array of soluble factors which can enhance tumor growth, we undertook this study to ascertain whether production of soluble factors by the tumor may also inhibit growth in an autocrine manner, and whether production of such factors is associated with the growth phase of the glioma. We observed that cell-conditioned medium (supernatants) from non confluent glioma cultures induced growth, while confluent culture supernatants produced pronounced growth suppression. These latter supernatants enhanced proliferation of non-transformed astrocytes. Supernatants derived from all stages of confluency produced inhibition of lymphocyte proliferation. To characterize these factors, dialyzed supernatant was tested and found to continue to produce lymphocyte suppression but no glioma growth limitation. Growth of tumors in indomethacin or in acetylsalicylic acid to abolish prostanoid synthesis abrogated the inhibitory influence on glioma growth but only partially reversed the lymphocyte suppressive capacity. These studies suggest that gliomas do produce a growth phase dependent autocrine inhibitory factor(s), and that the production of these small molecular weight factors is at least partially under control of the cyclooxygenase pathway. PMID- 1506858 TI - Physiological and biochemical studies on the cerebellar cortex of the murine mutants "jolting" and "motor end-plate disease". AB - The activity of cerebellar Purkinje cells in the murine mutants "jolting" and "med" has been determined using extracellular electrical recordings in vivo and in isolated cerebellar slices. Most of the cells in the mutant brains failed to generate simple spontaneous action potentials, but they responded to climbing fibre inputs by generating complex potentials. The few mutant cells that were spontaneously active exhibited much lower firing frequencies than normal cells, and interval histograms of spontaneous activity were skewed towards longer intervals. The silent cells in mutant cerebellar slices could be activated by direct intracellular stimulation, by antidromic excitation and by the application of glutamate and high [K+]0. Activity was not restored by the application of bicuculline. It seems that the failure of the cerebellar Purkinje cells to generate simple spontaneous action potentials is not due to an inherent inexcitability of the soma or to the excessive activity of GABA-ergic inputs onto the cells. It is suggested that an abnormality in the behaviour of a Ca2+ channel is the most likely origin for the deficit in these mutant mice. PMID- 1506859 TI - Phospholipids in X-linked adrenoleukodystrophy white matter: fatty acid abnormalities before the onset of demyelination. AB - Changes in fatty acid composition of complex lipids were analyzed in postmortem white matter from a patient with late onset adrenoleukodystrophy (ALD). The specimen showed three regions with progressive myelin breakdown: morphologically normal white matter; areas with active demyelination and perivascular lymphocyte and macrophage infiltration; and areas with marked gliosis. In the morphologically intact region, cholesterol esters were similar in amount and fatty acid composition to those in control tissue, although marked changes were observed in the actively demyelinating area. Galactolipids in these areas were also similar to those in controls. In contrast, glycerophospholipids were increased in amount and in very long chain fatty acids (VLCFA), which are the hallmark of ALD, at the active edge of the demyelinative lesion and even in the apparently intact sample. Further fractionation of the glycerophospholipids by high performance liquid chromatography showed a significant (up to 39-fold) accumulation of hexacosanoic acid (C26:0) in phosphatidylcholine, but not in other phosphatidyl derivatives. The consistent increases in phosphatidylcholine VLCFA in all samples from the ALD brain, which are postulated to represent progressive stages in the development of the disorder, suggest that phosphatidylcholine may be involved in antigen formation and may underlie an immunological basis for the pathogenesis of ALD. PMID- 1506860 TI - Effects of chronic catecholamine depletions on muscarinic M1-receptor and its mRNA in rat brain. AB - In order to compare the effects of total catecholamine (CA) or noradrenaline (NA) depletions on cholinergic systems, and the mechanisms of receptor regulation in various brain regions, the regional changes in the levels of acetylcholine (ACh), M1-receptor (M1-R) binding, and M1-R messenger RNA (mRNA) were mainly examined in rats which had received either repeated reserpine treatment or a single injection of the selective noradrenergic neurotoxin N-2-chloroethyl-N-ethyl-2-bromo benzylamine (DSP-4). The levels of dopamine (DA), its metabolites, NA, binding to both D1 and D2 sites, and the mRNA encoding the D2 receptor were also measured. Administration of reserpine (0.5 mg/kg/day, s.c.) for 2, 7 and 14 days depleted DA and NA in virtually all brain regions, while the short-term treatment increased DA metabolites in the striatum (at 2 days) and basal forebrain (at both 2 and 7 days). Administration of DSP-4 (50 mg/kg, i.p.) resulted in a specific loss of NA in the brain 10 days after the injection. These DSP-4 treated rats showed no change in the levels of ACh or M1-R except for an increase in ACh in the frontal cortex. In contrast, numerous changes in cholinergic indices were seen in the reserpine treated groups, and these changes varied from region to region of brain and with the length of drug treatment. In the striatum, ACh levels were increased in rats treated for 2 or 7 days but were normal after 14 days. M1-Rs were decreased at 14 days. These changes suggest that striatal DA, initially released by reserpine, inhibits the release of ACh from striatal cholinergic interneurons, while prolonged depletion of DA relieves this inhibition, leading to a subsequent down-regulation of M1-Rs. In the frontal cortex, ACh and M1-R levels were all decreased by reserpine treatment for 2 or 7 days, and the M1-Rs remained depressed at 14 days. In the basal forebrain, which contains the cholinergic cells that project to the cortex, DA metabolism was increased by 2 or 7 day reserpine treatment. This increased DAergic activity in the basal forebrain may facilitate cholinergic neurons, causing increased release of ACh in the frontal cortex. This, in turn, may lead to a down-regulation of the M1-Rs in that region. The levels of mRNAs encoding M1-Rs were increased in the striatum and frontal cortex by reserpine treatment, despite the decreases in the M1-Rs themselves.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1506861 TI - Daytime sleepiness after long-term continuous positive airway pressure (CPAP) treatment in obstructive sleep apnea syndrome. AB - A modified maintenance of wakefulness test was performed in 58 patients with obstructive sleep apnea (OSA) syndrome before treatment and after long-term (554 +/- 28 days) home therapy with nasal continuous positive airway pressure (CPAP). Before treatment the patients had a shorter mean sleep latency than controls (16 +/- 1 vs. 27 +/- 1 min, mean +/- SEM, P less than 0.001). After treatment, the mean sleep latency increased to 20 +/- 1 min (P less than 0.002 as compared to baseline), but was still shorter than in controls (P less than 0.001). The incomplete normalization of the mean latency contrasted with the patients' claim that they no longer felt sleepy. The improvement in daytime alertness was significantly correlated with the reduction in sleep fragmentation after CPAP treatment and with the baseline mean sleep latency. These results support the hypothesis that sleep disruption related to respiratory events plays a role in the pathogenesis of daytime sleepiness. PMID- 1506862 TI - Imipramine induced lipidosis and dexamethasone effect: morphological and biochemical study in normal and chronic GM2 gangliosidosis fibroblasts. AB - A large heterogeneous group of lysosomotropic compounds with a common cationic amphiphilic structure induces in vitro and in vivo lysosomal lipid storage. The biochemical mechanism underlying the lipidosis is still the subject of investigation. The authors report the experimental effect of imipramine and dexamethasone on lysosomal system in cultured skin fibroblasts. Morphological and ultrastructural observations of cells treated with imipramine showed vacuoles with lipidic storage, enlarged lysosomes with electron translucent zones and normal appearance of all the other cytoplasmic organelles. The lysosomal enzyme activities were decreased on biochemical study. On the contrary, an increased enzyme activity was detected in the culture medium. Pretreatment with dexamethasone partially prevented the effect of imipramine. Our results suggest that tricyclic antidepressants may induce lysosomal lipidosis through a dysfunction in the recycling of mannose-6-phosphate receptors and in the trafficking of newly synthesized lysosomal enzymes. Moreover the data presented may provide a clue in understanding some of the side effects observed in patients chronically treated with antidepressant drugs. PMID- 1506863 TI - Comparison of the effects of selective and nonselective muscarinic agonists on cognition and thermoregulation in primates. AB - Peripheral toxicity may explain the disappointing therapeutic effects of nonselective muscarinic agonists in Alzheimer's disease. Partial agonists might exhibit an improved therapeutic index. We compare the central and peripheral cholinergic effects of RS86 with the M1/M3 partial agonists AF 102B and L-689,660 ((-)-3-[2-6 chloropyrazin)yl]-1-azabicyclo[2.2.2]octane) in primates. Administration of RS86 (1.5-2.25 mg/kg i.m.) or L-689,660 (0.1-0.3 mg/kg i.m.), but not AF 102B (up to 6 mg/kg i.m.), caused partial reversal of the disruptive effects of scopolamine on cognition. However, performance remained significantly poorer than in untreated control animals. Adverse effects prevented examination of higher doses. Centrally-mediated hypothermia was induced by RS86 (0.05 mg/kg p.o.) and L-689,660 (0.01 mg/kg p.o.) but only by a high dose of AF 102B (7 mg/kg p.o.). The putative therapeutic advantages of partial M1/M3 agonists over RS86 are discussed. PMID- 1506864 TI - Elevated levels of fibronectin in the CSF: what do they signify? PMID- 1506865 TI - Acute disseminated encephalomyelitis following HTLV-I associated myelopathy. PMID- 1506866 TI - MRI findings of multiple sclerosis with acute transverse myelopathy. AB - We classified clinically definite multiple sclerosis (MS) patients who underwent brain MRI with superconductive magnet into 2 subgroups: group A, consisting of 14 patients who had shown acute transverse myelopathy (ATM) during the course of illness; and group B, 35 patients without ATM, and the same neuroradiologist, blinded to clinical profiles of the patients, investigated the MR scans. We analyzed some parameters such as distribution, size, shape and number of the lesions. Although the total number of lesions were similar in each group, and the number of small size or patchy shape solitary lesions were not different, the moderate, large, ovoid or confluent lesions were lower in number in group A, compared with group B. The degree of cerebral white matter lesions and periventricular lesions were higher in group B. Brainstem lesions were significantly less common in group A. These results show characteristic differences in MR-detected, possibly pathological, changes between these 2 groups, and support our previous report that group A may constitute a distinct subgroup in patients with MS. PMID- 1506867 TI - Hemi-parkinsonism in multiple system atrophy: a PET and MRI study. AB - We selected 6 patients presenting with hemi-parkinsonism from a total of 20 patients with probable multiple system atrophy (MSA) and studied their nigrostriatal lesions using magnetic resonance (MR) imaging and positron emission tomography (PET) with 18F-labeled 2-deoxy-2-fluoro-D-glucose (FDG). T2 weighted MR images demonstrated a decreased signal intensity in the putamen of all patients. This decreased signal was more intense in the nucleus contralateral to the affected body side in 5 patients. A decreased signal in the substantia nigra was found, expanding more on the contralateral side in 3 patients. T1-weighted images showed that the contralateral putamen was smaller in size than the ipsilateral. These findings indicated that the iron deposit and the neuronal cell loss in the degenerative process were more remarkable in the contralateral nuclei. FDG uptake in 5 patients had likewise declined more in the contralateral than in the ipsilateral putamen. The study shows that these patients have the nigrostriatal lesions as described in previous reports on MSA and that an asymmetric lesion relating to clinical signs is present in the nigrostriatal system. When a patient presents with hemi-parkinsonism alone, MR imaging and PET/FDG are useful for the clinical diagnosis of MSA. PMID- 1506868 TI - Quantitative EEG mapping and PET in Alzheimer's disease. AB - Quantitative analysis of topographical EEG was studied in comparison with measurement of regional glucose metabolism by PET in 42 patients with clinical diagnosis of probable dementia of Alzheimer type (AD) and in 15 age-matched normal controls. Measures analyzed included global and regional data from areas typically affected and not affected by AD pathology. While disturbance of metabolism followed a typical regional pattern, relative alpha, theta and delta power were more globally altered without selectivity for specific regions. Separation between AD and age matched controls by relative theta power was correct in 86% and was close to that by temporo-parietal glucose metabolism (correct classification 87%). Relative theta power as well as temporo-parietal glucose metabolism were significantly correlated (tau B = 0.54 and -0.53, respectively) to severity of AD assessed by the global deterioration scale. These results indicate that EEG measures may be used with an accuracy close to metabolic values from PET for the assessment of severity of AD. PMID- 1506869 TI - Immunoreactive parvalbumin concentrations in parahippocampal gyrus decrease in patients with Alzheimer's disease. AB - By using a sensitive enzyme immunoassay system for rat parvalbumin, we determined parvalbumin contents in the 4 cerebrocortical regions (superior frontal gyrus of frontal lobe, parahippocampal gyrus of temporal lobe, superior parietal lobule of parietal lobe, and calcarine area of occipital lobe) of patients with Alzheimer's disease and age-matched controls. Among the 4 regions, concentrations of parvalbumin were the highest in calcarine area (68.6 +/- 6.7 ng/mg protein, rat parvalbumin equivalents, mean +/- SE) and the lowest in the parahippocampal gyrus (11.0 +/- 1.7 ng/mg protein) in the controls. A similar regional difference of the concentration was observed also in the patients with Alzheimer's disease. When compared with the controls, however, concentrations of parvalbumin in parahippocampal gyrus of patients with Alzheimer's disease (4.0 +/- 0.9 ng/mg protein) were significantly low (P less than 0.01), showing less than a half of the control values. In contrast, the concentrations in the 3 other regions showed little difference between Alzheimer's disease and the controls. PMID- 1506870 TI - Thalamic amnesia: Korsakoff syndrome due to left thalamic infarction. AB - In order to support the concept that a lesion of the thalamus is sufficient to cause a Korsakoff syndrome, we are presenting 5 patients, all of whom developed the syndrome after sustaining a left (dominant) thalamic infarction. Two patients had pure thalamic strokes followed by a permanent Korsakoff syndrome. One of these patients was studied with neuropsychometric testing, as well as with a modern MRI scan. In 2 other patients, clinical and imaging data indicate that infarction was not limited to the thalamus. Another patient had bilateral thalamic infarcts but only a temporary Korsakoff syndrome. Neuropathological data are needed to elucidate the exact anatomical substrate of dominant thalamic Korsakoff syndrome. PMID- 1506871 TI - Surface electromyographic study of idiopathic cranial dystonia focused on the orbicularis oculi muscles. AB - We studied 115 Japanese patients with idiopathic cranial dystonia (Meige disease), using surface electromyography (EMG) focused on the orbicularis oculi muscles to classify the findings of the abnormal involuntary movements of this disease and to evaluate the pathophysiology of blepharospasm (BS). Surface EMGs at rest and at voluntary eyelid opening after eyelid closing were investigated. We found 62 (53.9%) patients exhibiting the overblinking type, 37 (32.2%) the tonic BS type, and 16 (13.9%) the normal type of behavior, considering the frequency of spontaneous blinking and presence of spasms. The present results suggest that BS is not a summation of blinking but a spatial and temporal extension of the orbicularis oculi muscle activity engaging in blinking, and the classification of the present study can support the investigation of the temporal characteristics of patients with this disease. PMID- 1506872 TI - Pathological changes in skeletal muscle in HTLV-I-associated myelopathy. AB - The main lesion site of HTLV-I-associated myelopathy or tropical spastic paraparesis (HAM/TSP) is the pyramidal tract. In some HAM patients, clinical symptoms and findings indicate neuromuscular involvement, such as muscular atrophy, fasciculation, elevated serum creatine kinase (CK) or significant electrophysiological data. Cases of HAM/TSP complicated with polymyositis or motor neuron disease have been reported. But no investigation has been directed to muscular pathology in many patients of HAM/TSP. We conducted muscle biopsies on 13 HAM patients. Four patients showed neurogenic changes. Six patients showed histological findings indicative of inflammatory myopathy. We investigated surface marker of invading cells in these 6 patients. In all patients, T lymphocytes were more predominant than B lymphocytes and in three of them T helper/inducer cells were more predominant than T suppressor cells. In 2 patients, only slight myopathic change could be seen, such as variation in fiber diameter and increase in the number of internal nuclei. In 1 patient, type 2 fiber atrophy was seen, and was possibly the result of disuse. Disturbance of secondary motor neurons or inflammatory myopathy is thus shown to be possibly associated with HAM/TSP. PMID- 1506873 TI - Modification of cervical dystonia by selective sensory stimulation. AB - Cervical dystonia is often refractory to all forms of therapy. Many patients, however, are able to transiently abolish their spasms following a specific gesture that presumably enhances sensory input. Such observations prompted us to develop a protocol to determine if various forms of sensory stimulation could modify the motor control patterns in cervical dystonia. Surface EMG recordings of multiple neck and trunk muscles were obtained in 11 consecutive cervical dystonia patients. Baseline patterns of voluntary and involuntary muscle activation were established during a series of motor and non-motor tasks. The tasks were repeated during the application of vibratory or electrical stimulation to select muscle groups or to cutaneous and mixed nerves. Analysis of the results was made on the basis of paper and computer recordings of the data. Sensory stimulation decreased involuntary muscle activity and reduced spasms in 5 subjects. However, objective or subjective improvement usually occurred only after specific stimuli were applied to specific anatomical sites. In these cases, the protocol identified the site at which a specific sensory stimulus could be applied to control the dystonia. We conclude that selective sensory stimulation can beneficially modify cervical dystonia in some patients. Such findings warrant further investigation of the use of sensory stimulation for control of cervical dystonia. PMID- 1506874 TI - Protein energy malnutrition and the nervous system. AB - Protein-energy malnutrition (PEM), a natural ramification of poverty, continues to be a perennial source of concern to a large segment of the world population. The developing nervous system of a child is specially vulnerable to deprivations in nurture. Peripheral nerve and muscle derangements are clinically evident by weakness, hypotonia and hyporeflexia in accordance with severity and duration of PEM. Motor and sensory nerve conduction studies exhibit significant abnormalities and often furnish useful and ominous correlation with grades of PEM. The human sural nerve histology in cases of severe PEM is characterized by persistence of small myelinated fibres, striking failure of internodal elongation and significant segmental demyelination. Young rhesus monkeys are ideal experimental PEM models and they show myopathic EMG changes amenable to rehabilitation. Muscle pathology comprises obliteration of cross-striations, streaming of Z bands, increased interfibrillary spaces, mitochondriomegaly and small-for-age fibres. Radioisotope assays reveal anomalous incorporation into various nerve and muscle constituents. Central nervous system, specially the neuropsychological functions are affected in a lasting manner. Learning deficits, behavioural problems and manual indexterity are most obtrusive features. PMID- 1506875 TI - Evidence of subclinical brain influence in clinically complete spinal cord injury: discomplete SCI. AB - Previous studies of the neurocontrol of movement in spinal cord injury (SCI) subjects revealed that even those without volitional movement may retain some degree of preservation of distal brain influence. We previously defined a discomplete lesion as one which is clinically complete but which is accompanied by neurophysiological evidence of residual brain influence on spinal cord function below the lesion. In order to document the nature and extent of such neurocontrol, we recorded surface EMGs from multiple muscle groups to study patterns of motor unit activity in response to tendon vibration, activation of muscles below the lesion by reinforcement maneuvers above the lesion and by voluntary suppression of plantar withdrawal reflexes. We analyzed data from this brain motor control assessment (BMCA) procedure in order to describe the frequency of occurrence and characteristics of residual control in discomplete SCI subjects, comparing with findings in (clinically and neurophysiologically) complete and in (clinically and neurophysiologically) incomplete SCI subjects. From a group of 139 SCI subjects seen for management of spasticity, 88 had clinically complete lesions. Of these, 74 (84%) were discomplete as defined by responses to the above maneuvers. The selection of management and intervention strategies, whether physiological, pharmacological, behavioral or surgical, should give consideration to the high likelihood that clinically complete subjects may be neurophysiologically incomplete. PMID- 1506876 TI - Hypoxic neuropathy versus diabetic neuropathy. An electrophysiological study in rats. AB - In the experimental rat model of diabetes a slowing of nerve conduction velocity and a resistance to ischemic conduction failure have been found as an indication of polyneuropathy. The same electrophysiological abnormalities have been demonstrated in a model in which healthy rats are kept under hypoxic conditions (10% O2) for a 10-week period. Two factors are held responsible for the development of diabetic polyneuropathy: metabolic deterioration and hypoxia. However, until now the relative roles of metabolic deterioration and hypoxia in the development of polyneuropathy have not been settled. To test both explanations further with more sophisticated electrophysiological techniques, the H-reflex (motor and sensory NVC) and the stimulated SF-EMG (measures terminal nerve branch and neuromuscular transmission) were measured in 3 groups of 10 rats, a healthy control group, a diabetic group, and a hypoxic group, every 5 weeks, for 6 months. In the control rats an age-related increase in motor and sensory conduction velocity was found, whereas in the diabetic rats as well as in the hypoxic rats a marked decrease in sensory and a slight decrease in motor nerve conduction velocity was observed. The jitter measured in the stimulated SF EMG was significantly increased in both the diabetic and the hypoxic group. The results of the present study support the possible role of hypoxia, in addition to metabolic factors, in the development of experimental diabetic neuropathy. PMID- 1506877 TI - The relationship of nerve to myoblasts and newly-formed secondary myotubes in the fourth lumbrical muscle of the rat foetus. AB - The formation of normal numbers of skeletal muscle fibres depends on functional innervation of the muscle before and during the period of secondary myotube formation, but little has been known about the physical relationship between nerve terminals and the myoblasts and secondary myotubes over the critical period. This paper reports the results of a serial-section electron microscopic study of the IVth lumbrical muscle of the rat hindlimb, studied on embryonic day 20 (E20), a time when all secondary myotubes are less than 24 h old, and new ones are rapidly forming. Most myoblasts lying within the endplate region of the muscle received some direct neural contact; in almost all cases, the contact originated from an extension of a differentiated nerve terminal present at the endplate of an adjacent primary myotube. At six of 15 neural contact sites on myoblasts, primitive synaptic specialization was present. The newly-formed secondary myotubes were also directly, although sparsely, innervated in nine of ten instances. One secondary myotube was never seen to be innervated, despite extensive serial tracing. Nerve terminals passing to secondary myotubes were also principally derived from the innervation zone of the earlier-formed primary myotubes. Primary myotubes were profusely innervated by multiple axons. The results suggest that most nerve terminals are initially accommodated on the primary generation of myotubes, but progressively transfer to pre-fusion myoblasts or to secondary myotubes as these appear. In general, very young secondary myotubes are innervated by only a single axon, rather than being polyneuronally innervated. The existence of some secondary myotubes which lack any direct innervation suggests that intimate nerve contact may not be obligatory for formation of new secondary myotubes. PMID- 1506878 TI - The astrocyte--extracellular matrix complex in CNS myelinated tracts: a comparative study on the distribution of hyaluronate in rat, goldfish and lamprey. AB - The localization of hyaluronate was studied in the CNS of rat, goldfish and lamprey. Cryostat sections were incubated with glial hyaluronate-binding protein of human origin and stained by indirect immunofluorescence with glial hyaluronate binding protein antibodies not reaching with rat and fish. As previously reported for glial hyaluronate-binding protein and glial fibrillary acidic protein, hyaluronate and glial fibrillary acidic protein had a similar distribution in rat spinal cord and optic nerve, both substances forming ring-like structures around individual myelinated axons. A similar periaxonal distribution was observed in goldfish spinal cord and medulla, except that the rings were much wider, to accommodate the large goldfish axons. The glial fibrillary acidic protein positive neuroglial tissue forming distinctive structures in goldfish vagal lobes also stained for hyaluronate. In both rat and goldfish spinal cord, motoneurons were surrounded by a hyaluronate coat. Goldfish optic nerve and lamprey spinal cord were hyaluronate-negative and, as previously reported, they stained for keratin but not for glial fibrillary acidic protein. The findings suggest that hyaluronate in CNS fibre tracts in a product of glial fibrillary acidic protein positive neuroglia. They also suggest that the appearance of glial fibrillary acidic protein-positive neuroglia and the formation of a hyaluronate-bound extracellular matrix are related phenomena in phylogeny. PMID- 1506879 TI - Beta-like ganglion cells in the South American opossum retina: a Golgi study. AB - Using the Golgi technique we investigated the morphology of the ganglion cells of the South American opossum retina. We focused our attention on a type of ganglion cell which has a relatively small dendritic field diameter and a medium-sized soma, making it a morphological equivalent of beta ganglion cells of cat retina. Both radial sections of the retina, where the stratification level of ganglion cells dendrites can be observed in the inner plexiform layer (IPL), and flat preparations of the retina, where the whole dendritic field of the ganglion cells can be examined and quantified, have been studied. Usually these cells have one to three primary dendrites, giving rise to short spiny branches. The dendrites of these cells are segregated in two groups, one with dendritic trees arborizing in the inner two thirds and another group arborizing in the outer third of the IPL. The two groups of beta-like cells probably represent the physiological ON- and OFF-center types of ganglion cell as found in cat retina. The mean cell body and dendritic field diameters of 47 cells were 18.5 +/- 1.6 microns, (size range 16 21 microns) and 91.5 +/- 16 microns (range 54-133 microns), respectively. Cell body and dendritic fields sizes were homogeneous across the retina of the opossum. In the opossum the relatively large dendritic fields of the beta-like ganglion cells in the area centralis are consistent with the poor visual acuity of this species. PMID- 1506880 TI - Pathophysiology and treatment of focal cerebral ischemia. Part II: Mechanisms of damage and treatment. AB - The mechanisms that give rise to ischemic brain damage have not been definitively determined, but considerable evidence exists that three major factors are involved: increases in the intercellular cytosolic calcium concentration (Ca++i), acidosis, and production of free radicals. A nonphysiological rise in Ca++i due to a disturbed pump/leak relationship for calcium is believed to cause cell damage by overactivation of lipases and proteases and possibly also of endonucleases, and by alterations of protein phosphorylation, which secondarily affects protein synthesis and genome expression. The severity of this disturbance depends on the density of ischemia. In complete or near-complete ischemia of the cardiac arrest type, pump activity has ceased and the calcium leak is enhanced by the massive release of excitatory amino acids. As a result, multiple calcium channels are opened. This is probably the scenario in the focus of an ischemic lesion due to middle cerebral artery occlusion. Such ischemic tissues can be salvaged only by recirculation, and any brain damage incurred is delayed, suggesting that the calcium transient gives rise to sustained changes in membrane function and metabolism. If the ischemia is less dense, as in the penumbral zone of a focal ischemic lesion, pump failure may be moderate and the leak may be only slightly or intermittently enhanced. These differences in the pump/leak relationship for calcium explain why calcium and glutamate antagonists may lack effect on the cardiac arrest type of ischemia, while decreasing infarct size in focal ischemia. The adverse effects of acidosis may be exerted by several mechanisms. When the ischemia is sustained, acidosis may promote edema formation by inducing Na+ and Cl- accumulation via coupled Na+/H+ and Cl-/HCO3- exchange; however, it may also prevent recovery of mitochondrial metabolism and resumption of H+ extrusion. If the ischemia is transient, pronounced intraischemic acidosis triggers delayed damage characterized by gross edema and seizures. Possibly, this is a result of free-radical formation. If the ischemia is moderate, as in the penumbral zone of a focal ischemic lesion, the effect of acidosis is controversial. In fact, enhanced glucolysis may then be beneficial. Although free radicals have long been assumed to be mediators of ischemic cell death, it is only recently that more substantial evidence of their participation has been produced. It now seems likely that one major target of free radicals is the microvasculature, and that free radicals and other mediators of inflammatory reactions (such as platelet-activating factor) aggravate the ischemic lesion by causing microvascular dysfunction and blood-brain barrier disruption.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1506881 TI - Adult intramedullary astrocytomas of the spinal cord. AB - In this series, 25 adult patients with intramedullary astrocytomas were treated by radical excision alone. Six patients proved to have anaplastic astrocytoma; five of them died within approximately 2 years and the sixth has demonstrated disease progression. The other 19 patients were diagnosed as having low-grade astrocytoma (16 cases) or ganglioglioma (three cases); two of these had advanced preoperative neurological disability and died of medical complications. Fifteen of the remaining 17 patients have no clinical evidence of tumor recurrence after a mean follow-up period of 50.2 months; the other two have a small residual neoplasm that demonstrates no progression. Of these 17 patients, seven had previously received radiation therapy, but had clear evidence of tumor growth subsequently. This experience suggests that surgery is not beneficial for anaplastic spinal astrocytoma. However, in cases of low-grade tumor, radical excision is associated with minimal morbidity and an excellent long-term prognosis when carried out before significant disability occurs. PMID- 1506882 TI - Ultra-early evaluation of regional cerebral blood flow in severely head-injured patients using xenon-enhanced computerized tomography. AB - The role of cerebral ischemia in the pathophysiology of traumatic brain injury is unclear. Cerebral blood flow (CBF) measurements with 133Xe have thus far revealed ischemia in a substantial number of patients only when performed between 4 and 12 hours postinjury. But these studies cannot be performed sooner after injury, they cannot be done in patients with intracranial hematomas still in place, and they cannot detect focal ischemia. Therefore, the authors performed CBF measurements in 35 comatose head-injured patients using stable xenon-enhanced computerized tomography (CT), simultaneously with the initial CT scan (at a mean (+/- standard error of the mean) interval of 3.1 +/- 2.1 hours after injury). Seven patients with diffuse cerebral swelling had significantly lower flows in all brain regions measured as compared to patients without swelling or with focal contusions; in four of the seven, cerebral ischemia (CBF less than or equal to 18 ml/100 gm.min 1) was present. Acute intracranial hematomas were associated with decreased CBF and regional ischemia in the ipsilateral hemisphere, but did not disproportionately impair brain-stem blood flow. Overall, global or regional ischemia was found in 11 patients (31.4%). There was no correlation between the presence of hypoxia or hypertension before resuscitation and the occurrence of ischemia, neither could ischemia be attributed to low pCO2. Ischemia was significantly associated with early mortality (p less than 0.02), whereas normal or high CBF values were not predictive of favorable short-term outcome. These data support the hypothesis that ischemia is an important secondary injury mechanism after traumatic brain injury, and that trauma may share pathophysiological mechanisms with stroke in a large number of cases; this may have important implications for the use of hyperventilation and antihypertensive drugs in the acute management of severely head-injured patients, and may lead to testing of drugs that are effective or have shown promise in the treatment of ischemic stroke. PMID- 1506883 TI - Spinal arachnoid cysts in the pediatric age group: an association with neural tube defects. AB - Between 1979 and 1991, spinal arachnoid cysts were found in 11 patients aged 19 months to 18 years (mean age 5 1/2 years). Of the 11 patients, six had a myelomeningocele and one diastematomyelia. The presenting symptoms included radicular pain (one patient), progressive weakness (three), increasing scoliosis (one), worsening spasticity (three), and recurrent urinary tract infections and progressive constipation (one). Two patients showed no symptoms from the spinal arachnoid cyst. The distribution of lesions was as follows: cervicomedullary (one patient), cervical (one), cervicothoracic (two), thoracic (four), lumbar (two), and sacral (one). Four of the 11 arachnoid cysts (all intradural) were located anterior to the spinal cord, three of which were in children with a myelomeningocele. Only two of the cysts were extradural; both were found in the lumbosacral region, and one was associated with diastematomyelia. Eight patients were treated with fenestration and/or resection of the cyst wall. Three patients with anterior cysts were treated with shunts, a cyst-to-pleural space shunt in two and a cyst-to-subarachnoid space shunt in one. All of the patients either improved or exhibited an arrest in the progression of their symptoms. Spinal arachnoid cysts are a treatable cause of progressive neurological deficits and, in this series, were frequently found in patients with neural tube defects. PMID- 1506884 TI - Intractable pain of spinal cord origin: clinical features and implications for surgery. AB - The clinical features and types of pain affecting 127 patients with central pain caused by lesions in the spinal cord were studied and correlated with the results of surgical procedures performed on 103 of them. The surgical procedures consisted of percutaneous cordotomy in 39 cases, cordectomy in 12, dorsal root entry zone (DREZ) surgery in four, dorsal cord stimulation in 35, and brain stimulation in 13. The three most common types of pain in the 127 patients were characterized as: steady in 95% of cases, intermittent (usually shooting) in 31%, and evoked (allodynia, hyperpathia, or hyperesthesia) in 45%. Steady pain was usually causalgic (74.8%) or dysesthetic (27.6%). The only obvious clinical correlation with pain type was the association of intermittent pain with lesions at the T10-L2 vertebral level. Destructive surgery (cordotomy, DREZ surgery, or cordectomy) affected the three chief types of pain differently from treatment with cord or brain stimulation. Destructive surgery resulted in reduction of steady pain in 26% of affected cases, of intermittent pain in 89%, and of evoked pain in 84%, while stimulation resulted in pain reductions in 36%, 0%, and 16% of cases, respectively. The differential effect of destructive surgery on steady and intermittent pain is consistent with published experience. These observations suggest differing mechanisms for the three types of pain. PMID- 1506885 TI - Oblique sagittal magnetic resonance imaging visualizing vascular compression of the trigeminal or facial nerve. AB - An oblique sagittal magnetic resonance (MR) imaging method was developed to provide better visualization of vascular compression of nerves. The MR images of 12 patients with trigeminal neuralgia and 24 with hemifacial spasm were analyzed. The oblique sagittal views were obtained along the nerve identified by the axial view at an angle of 105 degrees between the line along the dorsal brain stem and the line along the margin of the pontomedullary junction (in patients with hemifacial spasm) or by the midsagittal view through the midpons (in patients with trigeminal neuralgia). The T1- and T2-weighted, proton-density, and/or gradient-echo MR images were evaluated to optimize imaging conditions. The oblique sagittal gradient-echo MR image most clearly visualized vascular compression of the nerves as high-intensity lines in six patients with trigeminal neuralgia, which was confirmed intraoperatively in four. Fifteen (75%) of 20 oblique sagittal gradient-echo MR images demonstrated vascular compression of the facial nerves in patients with hemifacial spasm; 12 of these were confirmed intraoperatively. The control study used 15 oblique sagittal gradient-echo MR images of nonaffected contralateral and normal sites. Four false-positive findings were found. Oblique sagittal gradient-echo MR images are a useful planning aid, allowing differential diagnosis prior to microvascular decompression in trigeminal neuralgia and hemifacial spasm. PMID- 1506886 TI - An artificial blood vessel with an endothelial-cell monolayer. AB - An artificial blood vessel with an endothelial-cell monolayer was used as an arterial substitute in rats. Endothelial cells were isolated from the aorta of a Wistar rat by the digestion method. The cell identification was established by the cobblestone appearance of a confluent cell monolayer, by an expression of factor VIII-related antigen, and by the presence of Weibel-Palade bodies. The luminal surface of the thin-walled polytetrafluoroethylene (PTFE) graft (4 mm in diameter and 10 mm in length) was coated with an endothelial-cell monolayer for 7 days in vitro. An interpositional graft was placed using the endothelial cell coated PTFE prosthesis on the right common carotid artery in seven rats. A total of 10 rats received an interpositional graft with the noncoated PTFE prosthesis as a control. The patency rate at 1 month after implantation was significantly higher in the coated group than in the control group. The vascular prosthesis with an endothelial-cell monolayer is a promising technique to inhibit the development of thrombosis. PMID- 1506887 TI - Selective blood-tumor barrier disruption by leukotrienes. AB - The authors have previously reported that intracarotid infusion of 5 micrograms leukotriene C4 (LTC4) selectively increases blood-tumor barrier permeability in rat RG-2 tumors. In this study, rats harboring RG-2 tumors were given 15-minute intracarotid infusions of LTC4 at concentrations ranging from 0.5 microgram to 50.0 micrograms (seven rats in each dose group). Blood-tumor and blood-brain barrier permeability were determined by quantitative autoradiography using 14C aminoisobutyric acid. The transfer constant for permeability (Ki) within the tumors was increased twofold by LTC4 doses of 2.5, 5.0, and 50.0 micrograms compared to vehicle alone (90.00 +/- 21.14, 92.68 +/- 15.04, and 80.17 +/- 16.15 vs. 39.37 +/- 6.45 microliters/gm/min, respectively; mean +/- standard deviation; p less than 0.01). No significant change in Ki within the tumors was observed at the 0.5-microgram LTC4 dose. Blood-brain barrier permeability was selectively increased within the tumors. At no dose in this study did leukotrienes increase permeability within normal brain. To determine the duration of increased opening of the blood-tumor barrier by LTC4 administration, Ki was measured at 15, 30, and 60 minutes after termination of a 15-minute LTC4 infusion (seven rats at each time point). The mean Ki value was still high at 15 minutes (92.68 +/- 15.04 microliters/gm/min), but declined at 30 minutes (56.58 +/- 12.50 microliters/gm/min) and 60 minutes (55.40 +/- 8.10 microliters/gm/min) after the end of LTC4 infusion. Sulfidopeptide leukotrienes LTC4, LTD4, LTE4 and LTF4 were infused to compare their potency in opening the blood-tumor barrier. The mean leukotriene E4 was the most potent, increasing the permeability value 3 1/2-fold compared with vehicle alone (139.86 +/- 23.95 vs. 39.37 +/- 6.45 microliters/gm/min). PMID- 1506888 TI - Antiproliferative cytokines secreted by lymphokine-activated killer cells stimulated with tumor cells. AB - Antiproliferative cytokine secretion by lymphokine-activated killer (LAK) cells during coculture with glioblastoma cell lines, autologous glioma cells, and nongliomatous tumor cell lines (Daudi and K562 cells) was assessed, as was the antiproliferative activity of the culture supernatants against the T98G (glioblastoma) cell line. A neutralization test using agents against interferon gamma (IFN-gamma), tumor necrosis factor (TNF), and lymphotoxin (LT) showed that antiproliferative activity was due to IFN-gamma, but not to TNF or LT. Nongliomatous tumor cells stimulated LAK cells to secrete cytokines, but gliomatous tumor cells did not. It was found that there is a discrepancy between the LAK cell capability to lyse malignant glioma cells and the ability to secrete cytokines. This may be due to the factors secreted by glioblastoma cells. PMID- 1506889 TI - Neuropeptide Y in the primate model of subarachnoid hemorrhage. AB - The cause of cerebral vasospasm after subarachnoid hemorrhage (SAH) remains unknown. Recently, an association between the potent vasoconstricting peptide, neuropeptide Y, and delayed cerebral vasospasm after SAH has been postulated. This was based on the findings of increased neuropeptide Y levels in the cerebrospinal fluid (CSF) and plasma after SAH in animals and humans. For this study, the primate model of SAH was used to assess the possible role of neuropeptide Y in delayed vasospasm after SAH. Fifteen cynomolgus monkeys underwent placement of a clot of either whole blood or red blood cells in the subarachnoid space around the middle cerebral artery (MCA). Sequential arteriography for assessment of MCA diameter and sampling of blood and CSF for neuropeptide Y were performed: before SAH (Day 0); 7 days after SAH, when signs of delayed cerebral vasospasm peak in this model and in humans; 12 days after SAH; and 28 days after SAH. Subarachnoid hemorrhage did not evoke changes in CSF or plasma levels of neuropeptide Y. Nine monkeys had arteriographic evidence of vasospasm on Day 7, but no change in neuropeptide Y levels occurred in plasma or CSF. In addition, neuropeptide Y levels did not change, even after resolution of vasospasm on Day 12 or Day 28. Neuropeptide Y levels were substantially higher in CSF than in arterial plasma (p less than 0.003 at each interval). No correlation was found between neuropeptide Y levels in CSF and in plasma. These results do not confirm a relationship between neuropeptide Y levels in the CSF or peripheral plasma and delayed cerebral vasospasm in SAH. PMID- 1506890 TI - Effects of vasopressin and oxytocin on canine cerebral circulation in vivo. AB - In vivo experiments on the vasoactive effects of vasopressin and oxytocin on cerebral circulation were carried out in anesthetized dogs, using an electromagnetic flowmeter to measure vertebral blood flow and angiography to measure the internal diameter of the basilar artery. Direct bolus infusion of 1 pmol to 1 nmol of vasopressin or 10 pmol to 10 nmol of oxytocin into a femoral vertebral artery shunt produced a dose-dependent decrease in vertebral artery blood flow without significantly affecting mean arterial blood pressure. Vasopressin was more potent than endothelin and neuropeptide Y, which have also been demonstrated to induce long-lasting decreases in vertebral artery blood flow. However, direct bolus infusion of vasopressin (100 pmol and 1 nmol) or oxytocin (1 nmol and 10 nmol) into the vertebral artery dilated major vessels including the vertebral, anterior spinal, and basilar arteries, as well as the circle of Willis and its main branches, while endothelin (1 nmol) and neuropeptide Y (5 nmol) caused no change in the diameters of major cerebral arteries. The V1 antagonist d(CH2)5tyrosine(methyl) arginine vasopressin suppressed the effects of both vasopressin and oxytocin. Vasopressin was over 10 times as potent as oxytocin in both assays. The vasodilatory effect of vasopressin, which may be mediated by an endothelium-dependent mechanism, was functionally damaged in dogs after experimental subarachnoid hemorrhage. These data suggest regional differences in the sensitivity and responsiveness of vasculature to vasopressin and oxytocin, and specifically that both peptides act through V1 receptors to decrease the resistance of large vessels and increase the resistance of small vessels. PMID- 1506891 TI - Reduction by delayed hypothermia of cerebral infarction following middle cerebral artery occlusion in the rat: a time-course study. AB - The effect of hypothermia on neuronal injury following permanent middle cerebral artery (MCA) occlusion in the rat was examined. Moderate hypothermia (body temperature 24 degrees C) was induced before MCA occlusion (0-minute delay group) in six rats, at 30 minutes in eight rats, and at 1 (seven rats), 2 (seven rats), and 3 (nine rats) hours after occlusion. The rats were kept at a 24 degrees C body temperature for 1 hour, then allowed to rewarm over 90 minutes. The animals were sacrificed 24 hours after MCA occlusion, and infarction was visualized by staining of coronal sections with 2,3,5-triphenyltetrazolium chloride. Infarct volumes were compared to matched normothermic control rats (body temperature 36 degrees C). Additional groups of 0-minute delay hypothermic (10 rats) and control animals (nine rats) were sacrificed 72 hours after MCA occlusion to examine the effects of prolonged survival. A significant reduction in the percentage of infarcted right hemisphere was seen in the animals sacrificed after 24 hours with 0-minute, 30-minute, and 1-hour delays in inducing hypothermia (mean +/- standard error of the mean: 2.2% +/- 0.7%, 4.4% +/- 0.9%, and 3.6% +/- 1.1%, respectively) as compared to normothermic control rats (10.8% +/- 1.5%, p less than 0.01 by Student's t-test). In the 2- and 3-hour delay groups, the percentage of infarcted right hemisphere was 17.1% +/- 2.4% and 12.0% +/- 2.7%, respectively, and no decrease in infarct volume was observed. The 0-minute delay hypothermia group sacrificed after 72 hours also displayed a significant reduction in right hemisphere infarct compared to their respective controls (4.8% vs. 11.7%, p less than 0.05). These findings indicate that, in the setting of permanent MCA occlusion, hypothermia markedly decreases brain injury even when its induction is delayed for up to 1 hour after the onset of ischemia. Ischemic damage does not appear to be merely retarded but permanently averted. PMID- 1506892 TI - Insulin and insulin-like growth factors in central nervous system tumors. Part V: Production of insulin-like growth factors I and II in vitro. AB - The authors have previously reported the presence of insulin-like growth factor (IGF) receptors in central nervous system (CNS) tumors and the production of IGF's and their binding proteins by CNS tumors in situ. This study was designed to investigate whether CNS tumor cells are capable of autocrine secretion of IGF I and IGF-II in vitro. Production of IGF's was studied by specific radioimmunoassay of tumor-cell-conditioned serum-free media from 34 CNS tumors: 12 gliomas, 12 meningiomas, and 10 miscellaneous tumors. Normal human serum and cerebrospinal fluid served as controls. Insulin-like growth factor I was detected in five of 12 meningiomas but in none of the gliomas studied. In contrast, IGF-II was detected in four of 12 gliomas and in six of 11 meningiomas studied. Four miscellaneous tumors produced IGF-I and/or IGF-II. These results suggest that CNS tumors differentially produce IGF-I and IGF-II in vitro. Preferential production of IGF's may be an important marker of the tumor-cell differentiation or malignancy and may be useful as a clinical diagnostic tool. These results add further support to the concept that IGF's may play a role in the regulation of the behavior of CNS tumors. PMID- 1506893 TI - Isolation and preliminary characterization of ACNU-resistant sublines of rat brain tumors in vivo. AB - Two variant cells lines resistant to the nitrosourea derivative ACNU ((1-4-amino 2-methyl-5-pyrimidinyl)-methyl-3-(2-chloroethyl)-3-nitrosourea hydrochloride), namely C6/ACNU and 9L/ACNU, were selected in vivo from rat brain tumors. Stable resistance to ACNU proved to be a characteristic of these cell lines, whether they were grown in vivo or in vitro. These cell lines exhibited a different pattern of cross-resistance to a wide range of chemotherapeutic agents with dissimilar chemical structures and mechanisms of action as compared with that of other ACNU-resistant cell lines established in vitro. Distinct cross-resistance was observed in both the C6/ACNU and 9L/ACNU cell lines to chloroethyl nitrosoureas such as BCNU (carmustine), CCNU (lomustine), and methyl CCNU and, additionally, to vincristine, vinblastine, Adriamycin (doxorubicin), and arabinosylcytosine, but not to bleomycin, methotrexate, cis-platinum, and 5 fluorouracil. This might point to a multifactorial mechanism of drug resistance in ACNU-resistant cell lines derived from rat C6 and 9L brain tumor cells. PMID- 1506894 TI - Effects of different methods of peripheral nerve repair on the number and distribution of muscle afferent neurons in rat dorsal root ganglion. AB - The effects of three methods of peripheral nerve repair and normal controls were compared with respect to the number and distribution of muscle afferent nerve cell bodies from the extensor digitorum longus muscle in the dorsal root ganglia of the rat. Nerves were repaired using one of three methods: 1) direct epineurial suture; 2) a three-strand cable graft; or 3) a coaxially aligned freeze-thawed autologous skeletal muscle graft. In all cases the number and distribution of muscle afferent nerve cells were estimated 300 days after nerve repair. Retrograde transport of horseradish peroxidase, injected into the extensor digitorum longus muscle, was used to identify muscle afferent nerve cell bodies in dorsal root ganglia exposed at laminectomy after fixation. It was found that all methods of nerve repair were associated with a change in both the number and distribution of labeled muscle afferent cell bodies. The number of labeled muscle afferent cells was significantly different from normal controls in all methods of repair, but was not significantly different among the three methods compared. On the other hand, cell size and cell distribution departed significantly more from normal after either of the grafting procedures than after direct repair. There was no significant difference between the two grafting techniques. These results are discussed with respect to their mechanistic and clinical interpretation. PMID- 1506895 TI - Direct embolectomy of the basilar artery bifurcation. Case report. AB - The case is presented of a 27-year-old man who developed a basilar artery bifurcation embolus encompassing Hilal microcoil as a complication following therapeutic embolization. An immediate direct surgical approach to the basilar artery bifurcation enabled the microcoil and associated thrombus to be removed and flow to be restored in the basilar artery and its distal branches. Postoperatively, the patient made a good recovery and on discharge was neurologically normal with the exception of a right third nerve palsy. This case suggests that in selected patients a direct surgical approach to the top of the basilar artery may be possible for treatment of emboli. PMID- 1506896 TI - Rebleeding from vertebral artery dissection after proximal clipping. Case report. AB - The authors present the case of a patient with vertebral artery dissection that rebled after being treated by proximal clipping. This is the second report of such a case. The results indicated that proximal clipping is not free from the risk of rebleeding, and a better alternative surgical technique should always be sought when treating vertebral artery dissections. PMID- 1506897 TI - Sinus pericranii: radiological and etiopathological considerations. Case report. AB - Sinus pericranii is a rare vascular anomaly involving an abnormal communication between the extracranial and intracranial circulations. A case of frontal sinus pericranii is presented which appeared to be a posttraumatic sinus because it developed 2 years after a cranial injury. However, the presence of vascular endothelium in the pathological examination and its association with a vascular anomaly (persistent trigeminal artery) suggested a congenital origin. The lesion, pericranial blood sinuses, and bone were totally removed. The computerized tomography, angiography, and magnetic resonance imaging findings are presented. The literature is reviewed and the pathogenesis of sinus pericranii is discussed. PMID- 1506898 TI - Facial pain due to vascular lesions of the brain stem relieved by dorsal root entry zone lesions in the nucleus caudalis. Report of two cases. AB - One patient with a pontine infarct due to a fusiform basilar artery aneurysm and one with an arteriovenous malformation within the tectum of the mesencephalon developed intractable facial pain. This pain was relieved in both patients by radiofrequency lesions in the dorsal root entry zone of the trigeminal nucleus caudalis. PMID- 1506899 TI - Retromastoid cisternal Ommaya reservoir for intrathecal therapy of coccidioidomycosis meningitis. Technical note. AB - A method is described that simplifies placement of an Ommaya reservoir for chronic access to the basilar cisterns. This technique is useful in treating coccidioidomycosis and other fungal meningitides. PMID- 1506900 TI - Treatment of fusiform intracranial aneurysms by circumferential wrapping with clip reinforcement. Technical note. AB - The authors describe a new technique for treating unclippable aneurysms. The method involves a modification of the traditional wrapping technique, including a clip-reinforced cotton sling. The results of this method in four patients are presented. PMID- 1506901 TI - Interhemispheric approach with callosal resection for distal anterior cerebral artery aneurysms. Technical note. AB - Distal anterior cerebral artery aneurysms are commonly found near the genu of the corpus callosum. While these aneurysms may be surgically obliterated through a variety of approaches, exposure via the interhemispheric fissure is used by many surgeons. Early identification of the afferent artery may be difficult with this approach, however, particularly if the aneurysm lies just beneath the genu of the corpus callosum. The authors have modified the interhemispheric approach to distal anterior cerebral artery aneurysms by electively exposing the feeding artery through a small anterior callosotomy. While this maneuver is not necessary for all distal anterior cerebral artery aneurysms, it can greatly enhance exposure in the region just below the genu of the corpus callosum. Experience with this technique in five patients is reported. In all cases, the limited anterior callosotomy enhanced surgical exposure. No morbidity could be attributed to the callosotomy in any patient. It is concluded that, when the interhemispheric approach is used, anterior callosotomy improves exposure of the region just below the genu of the corpus callosum and may be a useful maneuver when treating distal anterior cerebral artery aneurysms. PMID- 1506902 TI - Posteroventral pallidotomy for Parkinson's disease. PMID- 1506903 TI - Head injuries in golf: think first. PMID- 1506904 TI - International opportunities. PMID- 1506905 TI - AONE's first Nursing Administration Research Scholars. American Organization of Nurse Executives. PMID- 1506906 TI - Nurse administrators in job transition: negotiated resignations and severance agreements. PMID- 1506907 TI - The effects of implementing a professional practice model. AB - Professional practice is a reasonable and viable alternative to the traditional nursing practice models used in many hospitals. The authors describe the implementation of a professional practice model and its effects on cost per patient day, sick time, turnover rates, and job satisfaction indicators. PMID- 1506908 TI - The role of the Medicare fiscal intermediary and the regional home health intermediary, Part 2. AB - The Medicare fiscal intermediaries (FIs) are private insurance companies that serve as the federal government's agents in the administration of the Medicare program, including the payment of claims. There are two primary functions of the FI--reimbursement review and medical coverage review. Hospital-based home health agencies relate to the hospital's FI for reimbursement purposes. All home health agencies are assigned to a special FI, the Regional Home Health Intermediary (RHHI), for medical review issues. This may be the same FI or a different one than that audits the hospital's cost report. Freestanding home health agencies deal with separate reimbursement and medical review divisions within a single RHHI's office. The author reviews the role of the Medicare FI and the RHHI and their relationship to home health agencies. Part 1 was featured in the June issue. PMID- 1506909 TI - Redesigning roles for patient-centered care. The hospitality representative. AB - Nurses cannot always meet patients' expectations for nonclinical care. The authors describe the operational redesign of several hotel-related functions to enhance the provision of nonclinical care. This system enhances care delivery to better balance patients' perceptions of the clinical with the non-clinical components of care. PMID- 1506910 TI - A nursing management minimum data set. Significance and development. AB - Building on Werley's nursing minimum data set, the authors identified a nursing management minimum data set (NMMDS). This collection of core data elements is needed by nurse administrators to make management decisions and compare effectiveness across institutions. PMID- 1506911 TI - Strengthening hospital nursing, Part III. Differences among professional groups in the hospital planning process. AB - Interdisciplinary hospital planning processes are examined. Nurses, physicians, hospital administrators, and support and ancillary personnel from 75 hospitals participating in the national Strengthening Hospital Nursing Program indicate their perceptions of the project in relation to the centrality of the program in their hospitals, planning team development, and political issues. Differences and similarities among the professional groups are discussed. Additional articles on the Strengthening Hospital Nursing Program have appeared in the May and June 1992 issues of JONA. Part 1 explored the planning process in single and consortium hospital sites, and Part 2 examined the characteristics of effective planning processes. PMID- 1506912 TI - The process of VNA affiliation with a major teaching hospital. AB - Affiliation among agencies with differing staff, resources, organizational structure, policies, and programs is never easy. The author discusses major components of an affiliation between a visiting nurse association and its former competitor--a major teaching hospital. PMID- 1506913 TI - Organizational change from the "mom and pop" perspective. AB - Can hospitals successfully embark on large-scale organizational change without using outside consultants? Nursing administrators have an intense interest in the answer to this question. If change can be designed from inside the organization, the chances are greater that the change will fit better with the organization as a whole, and that buy-in by staff will be significant. The authors review the elements that need to be in place to conduct a successful change process internally, and support their concepts with a case study. PMID- 1506914 TI - Venture actualization in nursing. An analysis of innovation. AB - From innovations shared by nurse executives and nurse intrapreneurs in acute care hospitals, The Venture Actualization in Nursing Model emerged. Derived from a nursing perspective, this model captures the steps of the nurse innovation process, linking the nurse executive and nurse intrapreneur role components to the process that leads to venture success. PMID- 1506915 TI - Tough questions for consultants. PMID- 1506916 TI - JONA's Directory of Consultants to Nursing Administration. PMID- 1506917 TI - Optical resolution of (+/-)-all-trans-3-hydroxyretinal by use of high-performance liquid chromatography. AB - Racemic all-trans-3-hydroxyretinal (3-OH-RAL) (1) was converted by a reaction with (-)-camphanic acid chloride (CpCl) into a diastereomixture of camphanates (2a) and (2b) which was separated by preparative high-performance liquid chromatography (HPLC) to give two esters (2a) and (2b) in pure state, respectively. Saponification of (2a) and (2b) independently afforded optically active (3S)- and (3R)-3-OH-RALs (3a) and (3b), respectively, whose absolute structures were determined by circular dichroism (CD) spectra. Racemic 3-OH-RAL was separated to two peaks by HPLC using chiral column (ChiraSpher, Merck). Cochromatography with authentic specimens (3a) and (3b) showed that the peak with a short retention time corresponded to (3R)-isomer and the other to (3S). PMID- 1506918 TI - Effects of cyclic and continuous total enteral nutrition on 24-h rhythms of body temperature and urinary excretions. AB - To clarify the relationship between the pattern of diet intake and circadian rhythm in man, we measured body temperature and urinary excretions at 4-h intervals over a 24-h period in 18 patients who were in vegetative states and had been receiving total enteral nutrition (TEN) for at least 4 weeks. One group of patients was given a liquid diet intraduodenally and continuously throughout a day (continuous TEN), whereas the two other groups received their daily enteral feeding during a restricted time of day, either in the daytime from 0800 h to 2000 h (diurnal TEN) or in the nighttime from 2000 h to 0800 h (nocturnal TEN). In the diurnal TEN group, there was a clear body temperature rhythm with a peak at 2000 h, whose pattern was similar to the well-established body temperature rhythm in normal subjects. The nocturnal TEN group also showed a temperature rhythm, but the peak appeared at 0400 h. The continuous TEN group did not show any consistent body temperature rhythms. These effects of the schedule of TEN were quite similar to those on the circadian cortisol rhythm reported previously (J. Nutr. Sci. Vitaminol., 35, 639-647, 1989). In contrast to the body temperature rhythm, the rhythm of urinary excretions of water, sodium and potassium was little influenced by the schedule of TEN, showing a normal pattern with more excretions during the daytime in every group. Essentially the same effects were confirmed in a patient who received the three schedules of TEN in rotation for 5 weeks of each schedule.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1506919 TI - The influence of dietary medium and long chain triglycerides on growth performances and fat deposition in growing rats. AB - The present study was undertaken to investigate the effects of dietary medium and long chain triglycerides (MCT and LCT) on fat deposition and fatty acid composition of adipose tissues of rats. Twenty-seven Wistar strain male rats were divided into three groups and fed semisynthetic experimental diets: Basal (AIN 76), MCT (basal+C8:0 10%), LCT (basal+corn oil 10%). Feed intake was measured every day and body weight was measured once a week. At the beginning, 4th and 8th week of experimental feeding, 3, 12, 12 rats were slaughtered, respectively. Liver, perirenal and epididymal adipose tissue pads were weighted and their fatty acid composition was determined. Chemical composition of wholebody carcass was measured. Body weight gain was greater in rats fed the LCT diet than in rats fed the basal and MCT diets. Feed intakes were decreased in rats fed the MCT and LCT diets compared to that of the basal group. Subsequently, when compared to the basal group rats, feed efficiencies in rats fed the MCT and LCT diets were improved at the level of 6 and 14% for 4 weeks, and then 17 and 24% for 8 weeks, respectively. The weight of perirenal and epididymal adipose tissue pads tended to be larger in rats fed the MCT and LCT diets than in the basal group, although not significant. There were not significant differences in wholebody composition among the three groups. But it appeared that in rats fed the MCT diet, moisture content tended to be decreased and crude protein content increased compared to the LCT group rats. Fatty acid composition of the rats fed the LCT diet showed a good reflection of dietary fatty acid composition. Unlike LCT, little of medium chain fatty acid (MCFA) itself were incorporated into liver or adipose tissues. However, it seems that fat deposition of the MCT group was accomplished not by incorporation of dietary fatty acids but by de novo fatty acids synthesis. PMID- 1506920 TI - Protein and energy metabolism in patients with progressive muscular dystrophy. AB - Studies were made on whether body weight loss in patients with muscular dystrophy is due to reduced intake and/or abnormal expenditure of energy. For this, food intakes and various physiological variables were surveyed in totals of 310 patients with Duchenne muscular dystrophy (DMD) of 11 to 29 years old and 28 patients with limb-girdle muscular dystrophy (LGMD) of 30 to 47 years old. Energy and protein intakes, expressed on a unit body weight basis, in DMD patients were comparable to, or higher than the allowances for age-matched healthy controls, whereas those in LGMD patients were 92 and 94% respectively of these allowances. The basal metabolic rate (BMR), expressed as kcal/kg/day, of DMD patients of all ages was higher than that of controls, the difference increasing with age, and being about 20 to 30% higher than that of controls in older patients with DMD. The BMR of LGMD patients was nearly normal. The maintenance requirements of conventional dietary protein in DMD and LGMD patients were 1.26 and 0.84 g/kg/day, respectively. These values were about 68 and 12% higher than the normal adult value (0.75 g/kg/day), indicating decreased protein utilization and increased protein catabolism. Daily excretion of urinary 3-methylhistidine (3MH) per unit muscle mass (micrograms/mg creatinine) by MD patients was significantly higher than that by controls, indicating increased degradation of muscle protein. The BMR, maintenance protein requirement and 3MH excretion of DMD patients suggest that DMD is a hypercatabolic disease. Comparison of the energy and protein intakes with the allowances estimated in consideration of increased requirements showed deficiencies of energy and protein in DMD patients. Thus, we conclude that the underweight of the DMD patients resulted from nutrient deficiencies due to hypercatabolism, despite their considerably high intakes of energy and protein, expressed as per kg body weight. These deficiencies were confirmed by demonstrating decreased concentrations of free essential amino acids, particularly branched chain amino acids, in their serum. The values of variables of LGMD patients were intermediate between those of DMD patients and control subjects. PMID- 1506921 TI - Predictions of energy intake and energy allowance of patients with Duchenne muscular dystrophy and their validity. AB - Patients with Duchenne muscular dystrophy are so malnourished that energy supplementation is crucial. Their degree of energy deficiency was assessed as difference between their energy intake and their energy allowance, which were deduced from easily measured parameters. A significant, negative relationship was found between the basal metabolic rate (BMR) (Y, %, BMR/standard BMR) and body weight (X, %, body weight/standard body weight) in the patients, from which the formula for the BMR was deduced to be Y = -1.116X + 174.5 (n = 202, r = -0.72, p less than 0.001). Thus, it is possible to estimate the energy allowance for individual patients by a factorial procedure from the presumed BMR and a factor for physical activity. In addition, their energy intake was calculated from a constant protein-energy % (14.6%) in their diet and nitrogen intake which was deduced from a significant positive correlation between their nitrogen intake (Y, mg/kg/day) and their nitrogen excretion in 24 h urine samples (X, mg/kg/day). This correlation conformed to the equation Y = 1.053X + 32.4 (n = 267, r = +0.76, p less than 0.001). The validities of the above predictions for energy intake and allowance were examined by plotting the degree of energy deficiency (% ratio of presumed intake/presumed allowance) against the concentrations of retinal binding protein, prealbumin and transferrin in the serum, because rapid turnover proteins are sensitive to energy deficiency. Significant positive correlations were obtained with both variables, suggesting that these predictions were valid. PMID- 1506922 TI - Liver microsomal mixed-function oxidases in response to dietary whole egg protein levels in rats. AB - Relation between the activity of liver microsomal mixed-function oxidase system and dietary protein level was investigated in rats using purified whole egg protein, i.e. free from limiting amino acids. The animals were given either a diet containing 0, 5, 10, 20 or 40% of protein (experiment 1) or a diet containing 5, 10, 15 or 20% of protein (experiment 2) for 16 days. In experiment 2, half of the rats of each group were intraperitoneally injected sodium phenobarbital (PB) to induce the mixed-function oxidase system. The cytochrome P 450 content plateaued even at 5% level of dietary protein in experiment 1 and in the PB-untreated groups of experiment 2. However, it showed the highest value at 15% protein level in the PB-treated groups of experiment 2, indicating a shift of the response peak to a higher protein level due to an increase in protein requirement. Cytochrome P-450 reflected most specifically the dietary protein levels when the enzyme system was induced by PB. The 15% protein level, equivalent to 14.1 protein calories %, is a little higher than the optimal dietary level of whole egg protein ever obtained by usual nutritional indices. PMID- 1506923 TI - Nutritional assessment of a group of Japanese elementary school children in Tokyo: with special emphasis on growth, anemia, and obesity. AB - Anthropometric data, nutrient intake data, and blood biochemical parameters were analyzed for 66 elementary school children living in Tokyo, Japan, and their nutritional status was evaluated focusing on three problems: (1) zinc nutriture and growth, (2) anemia with iron deficiency, and (3) lipid nutriture and obesity. The subjects' mean energy and protein intakes met the recommended levels for Japanese children. However, their zinc intake levels were inadequate at 7.2, 8.3, and 8.5 mg in grades 2 (mean age: 8 yr), 4 (10 yr), and 6 (12 yr), respectively. Mean serum zinc concentration was 0.82 +/- 0.15 microgram/ml; the percentages of subjects who showed serum zinc concentration lower than 0.68 microgram/ml, the lower limit of the normal serum zinc concentration, were 28.6, 15.4, and 5.0% in grades 2, 4, and 6, respectively. These serum zinc concentrations indicated the existence of marginal zinc deficiency in some children, particularly in grade 2, though it was not severe enough to retard growth. Their iron intake levels (8.2, 10.2, and 10.2 mg for grades 2, 4, and 6, respectively) in combination with the proportion of iron intake from animal foods (37%) were judged to be adequate because no children showed serum ferritin, serum iron, or transferrin saturation levels lower than the criteria levels recommended for iron deficiency. Moreover, no definitely anemic children were found. Daily lipid intakes were 65.7, 74.5, and 78.3 g in grades 2, 4, and 6, respectively, and the mean percentage of energy intake from lipid to total energy intake, 32%, exceeded the level recommended. Mean serum total cholesterol concentrations and the percentage of subjects with elevated cholesterol levels (greater than or equal to 200 mg/dl) were high compared with the reported values. Means of the body mass index (BMI) and Rohrer Index (RI) for the subjects were slightly higher than Japanese standards. With these parameters for obesity, triglycerides and atherogenic index were positively correlated and HDL cholesterol and HDL cholesterol percentage to total cholesterol were negatively correlated. PMID- 1506924 TI - The effect of milk and skim milk intake on serum lipids and apoproteins in postmenopausal females. AB - The effects of milk and skim milk intake on serum lipids, apoprotein levels and fatty acid composition were investigated in postmenopausal females. After a 25 day intake of 200 ml/day of whole milk, the milk group had increased HDL and LDL cholesterol levels, with a slight decrease in the proportion of 18:0 fatty acids in the phospholipid fraction. The skim milk group, which had consumed 20 g/day of skim milk for 25 days, showed no changes. After intake of 400 ml/day of whole milk for 29 days, LDL, HDL and total cholesterol concentrations were even more increased and the VLDL-phospholipid concentration was decreased, with significant increases in apoA-I, apoA-II and apoB concentrations. In the skim milk group, consuming 40 g of skim milk per day for 29 days, total cholesterol, atherogenic index, HDL-triglyceride concentrations were decreased and HDL-phospholipid, apoA I and apoA-II concentrations were increased. Daily skim milk consumption, which is effective in preventing osteoporosis, and careful selection of foods should be recommended for Japanese postmenopausal women who consume more than 200 ml/day of whole milk. PMID- 1506925 TI - A pitfall in determining the globulin/albumin ratio in amaranth grains. AB - In amaranth grains (Amaranthus hypochondriacus L. and Amaranthus cruentus L.), there were two albumin (Alb) fractions, Alb-1 and Alb-2; Alb-1 was extracted with water or 0.5 M NaCl, and Alb-2 was extracted with water after extracting Alb-1 and globulin. The amount of Alb-2 comprised about 30% of the total albumin and globulin content. Little or no measurable protein corresponding to the amaranth Alb-2 was extracted from seeds of buckwheat (Fagopyrum esculentum Moench), quinoa (Chenopodium quinoa L.), or barley (Hordeum vulgare L. cv Sekitorisai-1). That the globulin/albumin ratio (G/A) in amaranth grains has been conflicting among investigators probably accounts for the consideration of Alb-2 during extraction. We here report the revised G/A ratio of 0.3-0.4. PMID- 1506926 TI - Effect of intraperitoneally administered nucleoside-nucleotide on the recovery from methicillin-resistant Staphylococcus aureus strain 8985N infection in mice. AB - The effect of intraperitoneally administered nucleoside-nucleotide on the recovery from methicillin-resistant Staphylococcus aureus (MRSA) strain 8985N infection was studied in mice. Mice fed nucleic acid-free 20% casein diet were administered intraperitoneally with a nucleoside-nucleotide mixture or with saline (control group) daily for 30 days. On the tenth day on this treatment, mice were challenged with the bacteria. The survival rates were 25% and 72% for the control and nucleoside-nucleotide groups, respectively. The recovery of the survived mice from the infection was confirmed by the increment of body weight and the reduction of the bacteria in the organs. The results show the effectiveness of the intraperitoneal administration of the nucleoside-nucleotide mixture for the recovery from the MRSA strain 8985N infection in mice. PMID- 1506927 TI - The impact of culture on psychotherapy: Korean clients' expectations in psychotherapy. AB - The impact of culture on clients' expectations for psychotherapy has not been adequately studied. This is the first study to explore Korean clients' expectations in psychotherapy. A 120-item instrument was used to collect data on expectations for psychotherapy held by 25 Korean clients of the Asian Mental Health Clinic. Six hypotheses regarding expectations for therapist's discipline, characteristics, techniques, goals, and roles in psychotherapy were examined. The findings indicate that the model that Koreans have for a psychotherapeutic relationship is similar to the special teacher-disciple relationship in Korea. The study demonstrated that psychiatric nurses are held in high regard by Korean clients. Education of Koreans to Western psychotherapy concepts and procedures is essential. Recommendations were made for different treatment modalities integrating Western concepts of psychotherapy with Korean cultural concepts of mental health. PMID- 1506929 TI - Nurses and the institutional ethics process. PMID- 1506928 TI - Guidelines for writing for publication. AB - Publishing is a worthwhile goal, achievable when separated into manageable steps and when the science and art of writing are addressed. The value of publishing is explored and several approaches to developing and publishing a manuscript are presented. PMID- 1506931 TI - Medical evaluation in "for cause" drug testing. PMID- 1506930 TI - Health locus of control and safety restraint attitudes in a sample of motor vehicle accident victims. AB - A study was undertaken to determine the health locus of control beliefs and the health promotion and safety restraint use attitudes of a sample of previously injured motor vehicle occupants. Health locus of control was not found to be related to more favorable attitudes toward safety restraint use and restraint use legislation. PMID- 1506932 TI - Colon and stomach cancer mortality among automotive wood model makers. AB - Automotive wood model makers have been reported to be at excess risk for colon and other cancers in recent epidemiologic studies. To further explore these risks, we conducted a retrospective cohort mortality study, with follow-up from 1940 through 1984, of 2294 white male wood model makers employed at any time until 1980 by three US auto makers. Using US mortality rates for comparison, we found elevated standardized mortality ratios of 1.2 (95% CI, 0.8-1.9) for colon cancer and 1.6 (95% CI, 0.9-2.6) for stomach cancer. We also conducted nested case-control studies for 20 colon and 17 stomach cancer cases and 543 age-matched controls. We found no trend of increased risk for colon or stomach cancer mortality with increased exposure to wood dust or to duration employed in wood model making. PMID- 1506933 TI - Using a low-cost, prize-drawing incentive to improve recruitment rate at a work site smoking cessation clinic. AB - A major obstacle in promoting smoking cessation programs through work sites is recruiting adequate numbers of smokers. We used a quasi-experimental design to evaluate the effect of a low-cost incentive (a prize drawing) for attracting participants to a smoking cessation clinic offered at multiple work sites. Sixty eight automobile dealerships were randomized to either a "prize" or control group. Smokers employed at work sites in the prize group were offered a chance to win a dinner for two for participating in a smoking cessation clinic. In November 1986, a questionnaire assessing tobacco use habits was sent to 3432 employees of the 68 work sites. A cohort of 844 smokers was identified from a total of 1986 employees who returned surveys. All smokers received registration materials to participate, free of charge, in one of three smoking cessation programs held in June 1987. The overall employee participation rate in the smoking cessation program was 6.6% (n = 56) with an overall work-site participation rate of 37.3% (n = 25). The rate was nearly identical in the "prize" and control groups (employee rate: 6.3% versus 6.7%; work-site rate: 39.4% versus 35.3%, respectively). PMID- 1506934 TI - Freon injection injury to the hand. A report of four cases. AB - During a 6-month period, the poison center was consulted on three occasions for advice regarding accidental injection of hexafluorethane (Freon) used in the manufacturing process of athletic shoes. A fourth case was later identified after consulting physicians near the manufacturing facility. Little information exists in the medical literature concerning injection of freon or other volatile substances. In each of these cases, workers inadvertently injected concentrated hexafluorethane into a finger while holding the shoe component and attempting to inject hexafluorethane. Each case presented with edema, limitation of motion, and crepitation. Hand roentgenogram revealed subcutaneous gas. Treatment was nonsurgical, consisting of splinting, tetanus immunization, and antibiotics. Rapid resolution of symptoms occurred in all four cases. Hexafluorethane is relatively inert when injected and has low toxicity. However, potential rapid expansion warrants observation for pressure injury. PMID- 1506935 TI - Occupational wood dust exposures, lifestyle variables, and respiratory symptoms. AB - The quantitative relationship of occupational exposure to airborne wood dust with nasal and pulmonary health problems is not clearly established, particularly for low to moderate exposures in the wooden furniture manufacturing industry. We examined the associations of pulmonary and nasal symptoms, wood dust exposure, and lifestyle variables (cigarette smoking, alcohol use, overweight, physical inactivity, and stress) in a sample of 168 woodworkers. Levels of wood dust exposure were not systematically associated with symptoms. Statistically significant associations were found for cigarette smoking; after controlling for the effects of smoking, heavy drinking was significantly associated with pulmonary symptoms, and perceived stress was associated with both pulmonary and nasal symptoms. These findings suggest that studies of the effects of low-level occupational wood dust exposures should control for the potential effects of lifestyle variables. PMID- 1506936 TI - Preliminary evaluation of an employer-sponsored mammography screening program. AB - Recognizing the importance of early detection of breast cancer, the Dow Chemical Company initiated a breast cancer awareness program in 1988. Evaluation of operational aspects of mammography screening component revealed that about half (53%) of 1186 eligible women in the evaluation cohort took part, although participation was three times higher for active than for retired employees. Eleven per cent of participants were considered to have "positive" screens, ie, had roentgenogram films with suspicious areas, and at least 82% of these women had follow-up medical services within 1 year of screening, as determined by a review of group insurance claims records. Two women with positive mammograms were subsequently diagnosed and treated for breast cancer within 2 months of screening. None of the women with negative mammograms developed breast cancer in the subsequent year. The suitability of group insurance data resources for responding to health care delivery questions is discussed. PMID- 1506937 TI - Heart rate response of firefighters to actual emergencies. Implications for cardiorespiratory fitness. AB - Heart rate (HR) and oxygen consumption (VO2) responses during actual fire suppression emergencies were monitored in 10 male firefighters. These firefighters worked at 157 +/- 8 beats per minute (bpm) for 15 +/- 7 minutes. This was 88 +/- 6% of their previously determined HR max. Based on treadmill testing, the HR x VO2 relationship was established for each firefighter. The predicted VO2 derived from HR monitoring in actual emergencies was 25.6 +/- 8.7 mL.kg-1.min-1 or 63 +/- 14% of VO2 max (40.0 +/- 6.5 mL.kg-1.min-1). These values on the cardiorespiratory response to actual emergencies are very similar to results derived from studies employing fire-suppression simulations. Recommendations for the VO2 max of firefighters ranging from 33.5 to 42.0 mL.kg 1.min-1 that have been generated from simulation testing appear appropriate given the cardiorespiratory responses to actual emergencies. PMID- 1506939 TI - Health-risk behaviors of Army aircrew. AB - Data from the US Army Health Risk Appraisal Program were used to compare health and fitness levels in flight and nonflight personnel. Survey data collected from an aviation brigade, consisting of 428 aircrew and 899 support personnel, were compared with US Army summary statistics. Flight personnel scored better on evaluation of hypertension, stress, weight standards, and seatbelt use. However, the prevalence of smokeless tobacco use, heavy alcohol consumption, and driving after drinking or riding with someone who consumed alcohol was significantly higher in flight personnel. This study suggests that although Army aircrew have better lifestyle habits overall, high-risk behaviors have been identified that warrant further evaluation. PMID- 1506938 TI - Mortality of workers exposed to acrylonitrile. AB - A retrospective cohort study was carried out in The Netherlands to investigate the potential carcinogenic effects in humans of occupational exposure to acrylonitrile (AN). The total study group consisted of 6803 workers "from eight chemical plants and one control plant" of whom 2842 had been exposed to AN between January 1, 1956 and July 1, 1979 for at least 6 months. All workers were employed by one of eight chemical companies. An extensive review of the available industrial hygiene data was conducted to assess the magnitude of past exposure to AN, occurrence of peak exposures, exposure to recognized potential human carcinogens, and respirator use. The total cohort was observed for mortality until January 1, 1988. In collaboration with the Central Bureau of Statistics, the causes of death were traced for the workers who died before 01-01-1988. In the exposed as well as in the nonexposed cohorts the total mortality was lower than expected, based on national mortality statistics. The observed cancer mortality in the exposed cohort was similar to the expected mortality. Specific analyses were carried out to investigate dose-response relationships and latency for total mortality and lung cancer mortality. Overall, no indications were found for a carcinogenic effect in this cohort of workers exposed to AN. PMID- 1506940 TI - Musculoskeletal discomfort in grocery express checkstand workers. An ergonomic intervention study. AB - An intervention study of cashiers at a large grocery store was begun in response to employee symptoms of musculoskeletal discomfort, primarily shoulder, neck, and upper back pain, after introduction of a new express checkstand. The grocery company then instituted workplace changes directed at reducing stressful postures and the discomfort in the anatomical sites of primary concern. These changes were placement of a physical barrier to reduce trunk flexion from overreaching, installation of an adjustable keyboard to reduce static shoulder stress, and education of employees about good workplace practices to reduce musculoskeletal stress and fatigue. There was a statistically significant reduction in neck, upper back, or shoulder discomfort but not arm, forearm, or wrist discomfort. There was also a significant reduction in employee use of medication and days to recovery from discomfort but not in overall number of employees with symptoms or in hours able to operate the checkstand without discomfort. We found that ergonomic interventions, directed to the anatomical site of greatest employee concern, are likely to be effective, that employees were a good source of information on the ergonomic problems and solutions in their workplace, but that the overall approach must be iterative to achieve the maximum effect. PMID- 1506941 TI - Non-Hodgkin lymphoma and previous exposure to hexachlorophene: a case report. PMID- 1506942 TI - Acute cardiac ischemia in patients with syncope: importance of the initial electrocardiogram. AB - OBJECTIVE: To determine the prevalence of acute cardiac ischemia in emergency department (ED) syncope patients without chest pain and to determine which of these patients are at high risk for acute cardiac ischemia. DESIGN: Data were collected prospectively during a study of ED triage of patients who had had possible acute cardiac ischemia. Supplemental retrospective review of records was performed to differentiate syncope from dizziness. SETTING: Six hospital EDs in New England (two primary teaching hospitals in urban locations, two medical school-affiliated teaching hospitals, and two nonteaching hospitals in rural settings). PATIENTS: 5,762 patients had presented to the ED with chief complaints consistent with acute cardiac ischemia, including chest pain, shortness of breath, dizziness, and syncope. The study sample consisted of 251 patients who had had syncope and no chest pain. RESULTS: The prevalence of acute cardiac ischemia among the syncope patients was 7% (18 of the 251 patients). Univariate analysis revealed the following to have significant association with acute cardiac ischemia: ischemic abnormalities on the electrocardiogram (ECG) obtained in the ED (p less than 0.001), arm or shoulder pain on presentation (p less than 0.05), rales (p less than 0.1), and prior history of exercise-induced angina (p less than 0.05) or myocardial infarction (p less than 0.1). All 18 patients with acute cardiac ischemia had ischemic abnormalities (pathologic Q waves, ST-segment elevation or depression, or T-wave abnormalities) on their presenting ECGs. CONCLUSION: For syncope patients who have no chest pain or ischemic abnormality on the presenting ECG in the ED, acute ischemia appears to be unlikely. Admission to the cardiac care unit for these patients for possible myocardial ischemia is probably unnecessary. However, patients who have syncope and ischemic abnormalities on the ECG are at risk for acute cardiac ischemia, even in the absence of chest pain. Hospital admission to rule out myocardial infarction for these patients is prudent. PMID- 1506943 TI - Physician electrocardiogram reading in the emergency department--accuracy and effect on triage decisions: findings from a multicenter study. AB - OBJECTIVE: To determine how well physicians in emergency departments read electrocardiographic (ECG) ST-segment and T-wave changes and how this affects triage decisions. METHODS: In the emergency departments of six teaching and nonteaching hospitals, the authors prospectively collected physicians' ECG readings and clinical data for 2,320 patients presenting with possible acute cardiac ischemia from 1979 to 1981. RESULTS: Compared with electrocardiographers, the study physicians misread as normal 41% of abnormal ST segments and 36% of abnormal T waves, and misread as abnormal 14% of normal ST segments and 17% of normal T waves. Trainees were significantly more sensitive readers of T-wave changes but less specific readers of both ST-segment and T-wave changes when compared with other physicians. Suboptimal triage was more likely when abnormal ST segments or T waves were misread as normal (22% vs. 11%, p less than 0.001, and 18% vs. 14%, p = 0.08, respectively). Conversely, coronary care unit (CCU) admission for patients without acute cardiac ischemia was more likely when normal ST segments were misread as abnormal (23% vs. 13%, p less than 0.0001). CONCLUSIONS: Physicians in emergency departments often misread the ST segments and T waves of patients with possible acute cardiac ischemia. Misreading is related to suboptimal triage and unnecessary CCU admission. Training emergency physicians to make these distinctions more accurately could improve medical care and hospital utilization. PMID- 1506944 TI - Yield of the screening review of systems: a study on a general medical service. AB - STUDY OBJECTIVE: To determine the usefulness of screening reviews of the cardiopulmonary and gastrointestinal systems during medical admissions. DESIGN: Case series. SETTING: General internal medicine ward of a university hospital. PATIENTS: 550 consecutive medical patients were initially screened at admission. The authors excluded 265 patients with life-limiting medical conditions, and they studied 98 patients with no known cardiopulmonary disease and 207 patients with no known gastrointestinal disease. INTERVENTIONS: Positive responses to screening systems review questions were evaluated using a standardized testing algorithm. MAIN OUTCOME MEASURES: Numbers of new diagnoses; potential for patient benefit. MAIN RESULTS: The authors made 26 new diagnoses for 25 patients (95% confidence limits, 16 to 37 patients), two of whom may have gained years of life as a result. CONCLUSIONS: The absolute yield of the screening cardiopulmonary and gastrointestinal reviews of systems of 550 patients admitted to an internal medicine service of a university hospital was a new diagnosis in about 5% of patients. An estimate of the cost-effectiveness compares favorably with those of other accepted screening practices. PMID- 1506945 TI - Quitting smoking: reasons for quitting and predictors of cessation among medical patients. AB - OBJECTIVE: To describe why medical patients quit smoking and the methods they use. DESIGN: Cross-sectional and prospective cohort design. Patient smokers were enrolled in a study of physician counseling about smoking. One year later, 2,581 of the patients were asked about quit attempts and methods used. Of those, 245 former smokers whose quitting had been biologically validated were interviewed about why and how they had quit. SETTING: Offices of internists and family practitioners in private practice and a health maintenance organization. SUBJECTS: Consecutive sample of ambulatory patients who smoked. MEASUREMENTS AND MAIN RESULTS: Baseline questionnaires included demographic data, smoking history, and symptoms and diagnoses related to smoking. After one year, subjects were interviewed about smoking status and methods used in attempting to quit. Cessation was confirmed by biochemical testing. Those who had quit were asked about reasons for quitting. Seventy-seven percent of successful quitters gave health-related reasons for quitting and the quitters ranked "harmful to health" as the most important reason for quitting. In a multivariate analysis, those who had a college education, who had social pressures to quit, and who had greater confidence in being able to quit were more likely to have quit smoking one year later, while those who smoked their first cigarette within 15 minutes of awakening and who had more diagnoses related to smoking were less likely to have quit smoking one year later. Participation in a treatment program and having been counseled by a physician or nurse practitioner were positively related to successful quitting, while use of filters or mouthpieces was negatively related. CONCLUSIONS: Concerns about health are the most common reason patients give for quitting, and addiction is the most important barrier to quitting. Education, social pressure, provider advice, and formal programs, but not over-the-counter devices, appear to increase the chances that smokers will quit. PMID- 1506946 TI - Call nights and patients care: effects on inpatients at one teaching hospital. AB - OBJECTIVE: To determine whether the timing and number of patients admitted by internal medicine housestaff under a traditional call schedule affect the resource utilization and outcome of care for those patients. DESIGN: Retrospective cohort study, using existing computerized records. SETTING: University-affiliated 340-bed city/county teaching hospital. PATIENTS/PARTICIPANTS: 22,112 patients discharged from the internal medicine service who had been admitted by an on-call first-year resident between January 1, 1980, and December 31, 1987. MEASUREMENTS AND MAIN RESULTS: Admission after 5:00 PM was associated with decreased hospital length of stay (8.1%, p less than 0.0001), but increased total charges (3.1%, p = 0.007). The relative risk of inpatient mortality for patients admitted at night was 1.21 (p = 0.03). Patients of busier housestaff, as indicated by a larger number of on-call admissions, had lower total charges (1.7% decreased per admission) and no change in risk of inpatient mortality. While no linear relation was found between number of admissions and length of stay, analysis of nonlinear effects revealed that length of stay first rises, then falls as interns receive more on-call admissions. CONCLUSIONS: The number and timing of admissions by on-call internal medicine housestaff are significantly related to length of hospital stay, total charges, and likelihood of inpatient mortality at one teaching hospital. These variations should be considered in planning the reform of residency training programs. PMID- 1506947 TI - The effects of a low-cost intervention program on hospital costs. AB - OBJECTIVE: To assess the impact of a low-cost education and feedback intervention designed to change physicians' utilization behavior on general medicine services. DESIGN: Prospective, nonequivalent control group study of 1,432 admissions on four general medicine services over 12 months. Two services were randomly selected to receive the intervention. The other two served as controls. Admissions alternated between control and intervention services each day. Results were casemix-adjusted using diagnosis-related groups (DRGs). Three internists blinded to patient study group assignment assessed quality of care using a structured implicit instrument. SETTING: Four general medicine services at a university hospital. INTERVENTIONS: A brief orientation, a pamphlet of cost strategies and common charges, detailed interim bills, and information about projected length of stay and usual hospital reimbursement for each patient. PATIENTS/PARTICIPANTS: Each service was staffed by a full-time internal medicine faculty member, one third-year and two first-year internal medicine houseofficers, three medical students, and a clinical pharmacist. Physicians were assigned to services for one-month periods by a physician unaware of the study design. To prevent crossover, houseofficers assigned to a service returned to the same service for all subsequent general medical inpatient assignments. MEASUREMENTS AND MAIN RESULTS: Geometric mean length of stay was 0.44 days (7.8%) shorter for the intervention services than for the control services (p less than 0.01), and geometric mean charges were $341 (7.1%) less (p less than 0.01). Effects persisted despite using a more precise cost estimate or casemix adjustment. Intervention houseofficers demonstrated superior cost-related attitudes but no difference in knowledge of charges. Audits of quality of care detected no significant difference between groups. CONCLUSION: This low-intensity intervention reduced length of stay and charges, even under the cost-constrained context of the prospective payment system. PMID- 1506948 TI - Research, academic rank, and compensation of women and men faculty in academic general internal medicine. AB - OBJECTIVE: To evaluate the status of men and women faculty in academic general internal medicine, including their professional training, faculty responsibilities, research performance, academic rank, and compensation, to determine whether systematic differences exist by gender. DESIGN/SETTING: The authors analyzed responses to a 55-part questionnaire sent to all full-time general internal medicine faculty at the major teaching hospitals in the United States. Unadjusted means were generated for men versus women faculty in demographics, training background, hours of work, professional time allocations, institutional support, professional self-assessment, research performance, academic rank, and compensation. Means were recalculated after adjusting for other variables using multivariate methods. RESULTS: The authors found no significant difference in the frequency of fellowship training between men and women faculty. Women and men perform similar professional activities, but even after multivariate adjustment, women devote less time to research and perceive less research skill and institutional support for their research, but have similar numbers of grants, abstracts, and publications in refereed journals and have similar academic ranks. Women faculty, however, receive lower compensation than do men faculty, even after adjustment. CONCLUSION: While the characteristics of men and women faculty are quite similar, including those defining their academic productivity, important differences exist in research time, perceived institutional support, and compensation. These differences cannot be explained by such obvious factors as age differentials, academic rank, or hours of work per week. PMID- 1506949 TI - The heart of darkness: the impact of perceived mistakes on physicians. AB - OBJECTIVES: To describe how physicians think and feel about their perceived mistakes, to examine how physicians' prior beliefs and manners of coping with mistakes may influence their emotional responses, and to promote further discussion in the medical community about this sensitive issue. DESIGN: Audiotaped, in-depth interviews with physicians in which each physician discussed a previous mistake and its impact on his or her life. Transcripts of the interviews were analyzed qualitatively and the data organized into five topic areas: the nature of the mistake, the physician's beliefs about the mistake, the emotions experienced in the aftermath of the mistake, the physician's way of coping with the mistake, and changes in the physician's practice as a result of the mistake. PARTICIPANTS AND SETTING: Eleven general internists and medical subspecialists practicing at a community, university-affiliated hospital in Oregon. RESULTS: Themes emerging from analysis of the interviews were the ubiquity of mistakes in clinical practice; the infrequency of self-disclosure about mistakes to colleagues, family, and friends; the lack of support among colleagues; the degree of emotional impact on the physician, so that some mistakes were remembered in great detail even after several years; and the influence of the physician's professional locus of control on subsequent emotions. CONCLUSIONS: The perception of having made a mistake creates significant emotional distress for practicing physicians. The severity of this distress may be influenced by factors such as prior beliefs and perfectionism. The extent to which physicians share this distress with colleagues may be influenced by the degree of competitiveness engendered by medical training. Open discussion of mistakes should be more prominent in medical training and practice, and there should be continued research on this topic. PMID- 1506950 TI - Patient expectations and satisfaction with medical care for upper respiratory infections. AB - To describe the determinants of patient satisfaction with medical care, self administered questionnaires were given to a consecutive sample of 237 patients coming to an ambulatory care practice for the treatment of upper respiratory infections (URIs). Patients' most important goal was to obtain a diagnosis (57%). They usually got more reassurance, medication, and personal interest than they had expected (p = 0.0001). In a multivariate model, patients' satisfaction was related to the degrees of personal interest and reassurance they had received and to whether they felt they had received the right medication (r2 = 0.45, p = 0.0001). The authors concluded that patients with URIs generally want a diagnosis but are primarily satisfied by the personal interest, the reassurance, and the medication they receive. PMID- 1506951 TI - Integrating general medicine and rheumatology training in the outpatient setting: a practice model. AB - The authors describe a primary care-based educational and practice model that integrates general medicine resident education in outpatient rheumatology with specialty fellowship training. Compared with the use of traditional specialty clinics, the model provides better access and service to patients and more appropriate training for residents. Revenues from clinical service delivered by faculty-supervised residents and fellows support 80% of the operating costs and educational activities of the model. The conceptual framework for the model reconciles the educational goals and practice philosophies of general medicine and specialty training and is applicable to training in other predominantly outpatient specialty areas. PMID- 1506952 TI - A model for the diagnostic medical interview: nonverbal, verbal, and cognitive assessments. PMID- 1506953 TI - Sex and the teacher--learner relationship in medicine. AB - As the numbers of women medical students, residents, and faculty increase, sexuality in teacher-learner relationships will present challenges for individuals and institutions. Ethical and legal guidelines regarding sexual harassment and contact already exist for many medical schools, hospitals, and professional organizations, as well as state and federal law. Individuals and institutions can begin to address these issues through policy development and educational sessions addressing human sexuality, communication skills, and the process of becoming a physician. PMID- 1506954 TI - Hyperparathyroidism and pregnancy: case report and review. AB - In pregnant women with symptomatic hyperparathyroidism, parathyroidectomy should be undertaken during the second trimester. We feel that the woman who is initially diagnosed well into the third trimester should be treated medically unless the hypercalcemia worsens or other complications occur. Since the treatment of asymptomatic hyperparathyroidism itself is controversial, it is even more difficult to define the treatment plan for an asymptomatic pregnant patient who has primary hyperparathyroidism. However, a recent consensus panel recommended that young patients with asymptomatic hyperparathyroidism be treated surgically. Accordingly, we believe that the asymptomatic pregnant patient should also be treated surgically, preferably in the second trimester. Whether a patient is treated medically or surgically in these situations, the pregnancy should be considered high-risk. The neonate should be monitored carefully for signs of hypocalcemia or impending tetany. If the mother is treated medically to term (or if spontaneous or elective abortion occurs), the mother should be monitored for hyperparathyroid crisis postpartum. Sudden worsening of hypercalcemia can result from the loss of the placenta (active placental calcium transport may be somewhat protective) and dehydration. Finally, every effort should be made to make the definitive diagnosis early in pregnancy in order to initiate optimal management. The diagnosis should be suspected during pregnancy if the following conditions exist: appropriate clinical signs or symptoms (especially nephrolithiasis or pancreatitis), hyperemesis beyond the first trimester, history of recurrent spontaneous abortions/stillbirths or neonatal deaths, neonatal hypocalcemia or tetany, or a total serum calcium concentration greater than 10.1 mg/dL (2.52 mmol/L) or 8.8 mg/dL (2.2 mmol/L) during the second or third trimester, respectively. PMID- 1506955 TI - Dizziness in primary care patients. PMID- 1506956 TI - Talking to patients. PMID- 1506957 TI - Ethylene glycol poisoning. PMID- 1506958 TI - Necrotizing vasculitis in a patient with acquired immunodeficiency syndrome. PMID- 1506959 TI - Calcium pyrophosphate dihydrate crystal deposition disease of the temporomandibular joint: report of a case. PMID- 1506960 TI - Lipoma of the tongue with cartilaginous change: a case report and review of the literature. PMID- 1506961 TI - A modified Boley gauge for accurate measurement during maxillary osteotomies. PMID- 1506962 TI - Reducing operating time with use of a bone plate for advancement genioplasty. PMID- 1506963 TI - Use of absorbable sutures for facial skin wounds. PMID- 1506964 TI - The need for standardized photographs. PMID- 1506965 TI - Meeting the challenge of clinical interest groups. PMID- 1506966 TI - Temporomandibular joint arthroscopy: a 6-year multicenter retrospective study of 4,831 joints. AB - Four health outcomes (range of motion, pain, diet, and disability) were measured in six diagnostic categories (internal derangement with closed lock, internal derangement with painful click, osteoarthritis, hypermobility, fibrous ankylosis, and arthralgia) in a 6-year retrospective multicenter study of 4,831 temporomandibular joints having undergone arthroscopic surgery. After arthroscopic surgery, 91.6% of all patients had good or excellent motion; 91.3% had good or excellent pain reduction; 90.6% had good or excellent ability to maintain a normal diet; and 92% had a good or excellent reduction in disability. These health outcomes compare favorably with all other known treatments for these conditions. Also, the surgical technique was relatively free of complications (4.4%). PMID- 1506967 TI - Holmium:YAG laser arthroscopy of the temporomandibular joint. AB - A new pulsed midinfrared laser has become available for use in arthroscopic surgery of the temporomandibular joint (TMJ). This article reviews holmium:YAG (yttrium-aluminum-garnet) laser physics, its tissue effects, and reports initial experience with its use in TMJ arthroscopy. Because the Ho:YAG laser can precisely and rapidly resect cartilaginous tissues with only moderate necrosis, can function in a saline environment, and can be transmitted through conventional optical fibers, it has the potential of becoming a useful and adaptable system for TMJ arthroscopic surgery. PMID- 1506968 TI - Early surgical intervention for orbital floor fractures: a clinical evaluation of lyophilized dura and cartilage reconstruction. AB - Experience in the management of 77 isolated orbital floor fractures is presented. The transconjunctival approach was used exclusively to access the orbital floor and lyophilized dura and cartilage were used to reconstruct the floor, when indicated. Follow-up for an average of 36 months showed excellent cosmetic and functional results. A 20% complication rate was noted, which compares favorably with what is reported in the literature. There were no graft extrusions or infections and only one case of graft displacement. These findings support the concept of early treatment of orbital floor fractures, even in "minimally symptomatic" patients. Lyophilized dura and cartilage proved to be safe and effective materials for orbital reconstruction. PMID- 1506969 TI - Erosion and heterotopic bone formation after alloplastic temporomandibular joint reconstruction. AB - Twenty-three temporomandibular joint arthroplasties using metallic condylar prostheses were performed because of severe ankylosis (8 patients), segmental mandibular resections in tumor surgery (9 patients), and after extensive trauma (2 patients). A clinical and radiological follow-up study showed heterotopic bone formation in 52% of cases and glenoid fossa resorption in 43%. In one patient with rheumatoid arthritis the condyle eroded through the skull base 10 months after surgery. Seven prostheses (30%) were removed and/or exchanged during the average 27.6-month follow-up. PMID- 1506970 TI - Simultaneous otoplasty and temporomandibular arthroplasty. AB - By altering the standard postauricular incision for access to the temporomandibular joint (TMJ), a standard otoplasty can be performed simultaneously with TMJ arthroplasty. The procedure is described and results are presented. In six patients with at least a 2-year follow-up, the esthetic results have been stable. There has been no morbidity as a result of such simultaneous surgery. PMID- 1506971 TI - The incidence of total hip replacement in orthognathic surgery patients receiving short-term steroid therapy. AB - It is well known that long-term corticosteroid therapy can lead to avascular necrosis of the femoral head. There is suspicion among orthopedic surgeons that short-term, high-dose steroid use poses similar risks. The records of 2,773 patients (1,497 who had total hip replacement and 1,276 who had orthognathic surgery) were retrospectively reviewed. No hip replacements had been done in the orthognathic surgery group and none of the patients in the total hip replacement group had undergone orthognathic surgery. The use of short-course, systemic corticosteroids to reduce postoperative swelling in orthognathic surgery did not seem to cause avascular necrosis of the femoral head. PMID- 1506972 TI - Treatment of mandibular angle fractures using two mini dynamic compression plates. AB - Thirty patients with 31 fractures of the mandibular angle were treated by open reduction and internal fixation using two mini dynamic compression plates with self-threading screws placed through a transoral incision with transbuccal trochar instrumentation. None of the patients were placed into postsurgical maxillomandibular fixation (MMF) or training elastics. Complications requiring secondary surgical intervention occurred in nine fractures (29%). Three were early infections requiring incision and drainage, removal of the hardware, and postoperative MMF. One was a nonunion with malocclusion requiring application of a more rigid bone plate. Five fractures developed late chronic swelling and low grade infection requiring plate removal. Osseous union had occurred in these cases and no MMF was necessary. The use of two mini dynamic compression plates in the manner done in this study was found to be a relatively easy but unpredictable treatment for fractures of the mandibular angle. PMID- 1506973 TI - Histologic study of the fate of autogenous auricular cartilage grafts in the human temporomandibular joint. AB - Biopsies of 30 autogenous auricular cartilage grafts previously placed in 21 patients with ankylosis and arthropathy of the temporomandibular joint were studied. These joints were reoperated because of persistent pain and limitation of motion. Histologically, all grafts showed viability of the cartilage. Eighteen cartilage grafts placed after Proplast (Vitek, Inc, Houston, TX) or Silastic (Dow Corning, Midland, MI) implants had been removed, all showed foreign-body granuloma with coexistent intact cartilage grafts. This indicated that the autogenous auricular cartilage was resistant to the foreign-body reaction. All cartilage grafts were encased by fibrous tissue. This overgrowth of fibrous tissue may be responsible for the ankylosis. Seven grafts showed cartilaginous proliferation grossly and all showed proliferation histologically. The cartilage proliferation also may contribute to the persistent symptoms and recurrent limitation of joint motion. PMID- 1506974 TI - Temporalis muscle as a disc replacement in the temporomandibular joint of sheep. AB - Temporalis muscle flaps were evaluated in sheep. Flaps placed following discectomy were examined at 2, 4, 12, and 24 weeks. Histologic evaluation showed avascular necrosis and subsequent displacement and loss of tissue from the joint resulting in close contact between the condyle and fossa. Muscle flaps placed lateral to the joint in operative controls were examined at 4, 12, and 24 weeks. This muscle remained viable while undergoing fibrous replacement. Although the surface layers of the condyle and fossa were initially lost, the tissues were reformed with time. This experiment showed that in the sheep, temporalis muscle does not withstand functional loading within the joint. However, despite the lack of interpositional material, the condyle and fossa can remodel. PMID- 1506975 TI - A case of cheiloplasty--1864. AB - Six hundred twenty thousand American soldiers were killed in the Civil War- almost as many fatalities as in all wars from the American Revolution through Vietnam. Those soldiers who did not immediately succumb to their wounds often had injuries that taxed the skills and imagination of the surgeon. A case of extensive destruction of the lower face is presented. PMID- 1506976 TI - Comparison of the use of bulk to micro culture of cell preparations for lymphokine-activated cytotoxicity assays. AB - Different assay systems have been used to quantitate lymphokine-induced natural cytotoxic activity as a measure of immune status. This study compares the effects of inducing cytotoxicity in a bulk culture system, where effector cells are transferred to a micro culture well for assay, to a micro culture system where the effector cells are not transferred. The effector/target ratio for both the bulk and micro culture systems was calculated using the number of viable effector cells present at the time of target cell addition. After overnight incubation with interleukin-2 (IL-2), the lytic activity of murine spleen cells to targets using a micro culture system was increased two-fold over the bulk culture method. This increase was amplified further after 5 days of activation with IL-2, in that the micro culture system resulted in a four-fold increase in cytotoxic activity. The loss of some adherent cells in the bulk culture system did not explain the overall decrease in recovered cytotoxicity. The difference appeared to be related to cell loss during centrifugation. Therefore, the E/T ratios are different in the two systems if not corrected for the number of viable cells. PMID- 1506977 TI - Reduced levels of free testosterone in four Catania-type alloalbuminemic males. AB - We studied total testosterone, sex hormone binding globulin, and free testosterone in four males presenting an electrophoretically slow-moving genetic variant of albumin, the alloalbumin Catania. Free testosterone levels were lower in these cases, found in a year of observation, than those expected for the ages. This finding, which is not related to any disease and constantly not recognized in other males with various genetic variants, should induce consideration of a probable difference of the genetic variant in hormone binding. PMID- 1506978 TI - An improved method for monitoring efficacy of anti-retroviral therapy in HIV infected individuals: a highly sensitive HIV p24 antigen assay. AB - Circulating human immunodeficiency virus (HIV) p24 antigen levels were measured by a highly sensitive HIV p24 antigen-capture enzyme-linked immunosorbent assay (ELISA) in patients with acquired immunodeficiency syndrome (AIDS) and AIDS related complex (ARC) otherwise negative for HIV p24 antigen measured by a commercial antigen-capture ELISA. The assays were performed at baseline and at several intervals during treatment with either zidovudine (ZDV) or dideoxyinosine (ddl). To further enhance the rate of antigen detection, serum was pretreated with hydrochloric acid to denature antibody in immune complexes. Utilizing this assay system, we monitored these patients for drug efficacy. HIV p24 antigen levels obtained by using this sensitive assay decreased in 3 of 8 patients receiving ZDV during 8 weeks of ZDV treatment. Similarly, ddl administration was associated with a decrease of HIV p24 antigen levels in 3 of 5 patients. Thus, the use of the highly sensitive HIV p24 antigen assay permitted the monitoring of surrogate HIV p24 antigen as a measure of efficacy of anti-retroviral therapy in all of these patients who were otherwise HIV p24 antigen-negative at the onset of anti-retroviral therapy. PMID- 1506979 TI - Elevation of platelet-associated IgG in aplastic anemia. AB - We determined platelet-associated IgG (PAIgG) levels in patients with aplastic anemia, idiopathic thrombocytopenic purpura (ITP), iron deficiency anemia, and systemic lupus erythematosus (SLE), as well as in normal healthy adults as a control group. To determine PAIgG levels, we used a competitive micro enzyme linked immunosorbent assay, which had excellent reproducibility, recovery, and dilution. We confirmed its reliability by comparing it to the immunoradiometric assay. Both the aplastic anemia group (n = 27, mean +/- SD = 218.6 +/- 244.6 ng/10(7) platelets) and the ITP group (n = 82, mean +/- SD = 212.5 +/- 327.8 ng/10(7) platelets) had higher PAIgG levels than the SLE group (n = 4, mean +/- SD = 38.4 +/- 22.4 ng/10(7) platelets), iron deficiency anemia group (n = 10, mean +/- SD = 16.1 +/- 3.6 ng/10(7) platelets), and normal control group (n = 69, mean +/- SD = 16.1 +/- 3.6 ng/10(7) platelets. The higher platelet-associated IgG levels in aplastic anemia suggest that autoimmune mechanisms are involved. PMID- 1506980 TI - An enzyme immunoassay for determining plasma concentrations of didemnin B. AB - Didemnin A was conjugated at the amino terminus of the N-methylleucine residue, via the linkers N-succinimidyl-3-(2-pyridyldithio)-propionate and trans-1,4 maleimidomethyl-cyclohexane carboxylic acid, to keyhole limpet hemocyanin (KLH) and bovine serum albumin (BSA). The didemnin-KLH conjugates were used to hyperimmunize rabbits. The resulting high titer antisera were employed with didemnin-BSA conjugate-coated microtiter plate wells to develop an indirect competitive inhibition enzyme immunoassay (CIEIA) that was fully cross reactive with didemnin B. A CIEIA is described that is capable of detecting the drug in plasma from didemnin B-treated patients at concentrations down to 1-3 ng/ml. This simple, sensitive CIEIA has been employed to demonstrate plasma drug clearance profiles with samples from didemnin B-treated patients. PMID- 1506981 TI - Enzyme immunoassay and immunochemical characterization of pancreatic stone protein in human serum. AB - Monoclonal antibodies were raised against human pancreatic stone protein (PSP) and used for one-step enzyme immunoassay (EIA). PSP-S2-5 was employed as the standard in the assay. The assay's measurable range was 25-1,500 ng/ml and within run coefficient of variation was 3.7-6.4%. Analytical recovery of the assay was 101.5 +/- 5.65% (mean +/- SD). The results of experiments in which serum was fractionated by Mono S (cation exchange chromatography) suggested that most of immunoreactive material in human serum is PSP-S2-5. The EIA offers simple, rapid, and specific analysis of serum PSP level for clinical diagnosis. PMID- 1506982 TI - Effect of heat inactivation and sheep erythrocyte adsorption on the titer of anticardiolipin antibodies in primary antiphospholipid syndrome and healthy blood donors' sera. AB - The standard enzyme linked immunosorbent assay (ELISA) currently in use for detection of anticardiolipin antibodies (ACA) was used to evaluate the influence of heat inactivation and sheep erythrocyte adsorption on individual optical density (OD) of sera from healthy blood donors or patients with primary antiphospholipid syndrome. Each sample was tested after single or combined maneuvers as follows: adsorbed, adsorbed and inactivated, only inactivated, and compared to basal readings. A significant increase of ACA titers did occur after inactivation of normal sera, but adsorption had no effect. In contrast, neither inactivation nor adsorption changed ACA titer in primary antiphospholipid syndrome sera as a group, although in certain sera there were changes. This observation may suggest the presence in normal serum of a thermolabile factor which modulates ACA binding to its antigen and the reactivity of the anticardiolipin antibodies of the primary antiphospholipid syndrome with sheep erythrocyte membrane phospholipids. PMID- 1506983 TI - Tumor markers CA 19-9 and CA 195 are also useful as markers for cystic fibrosis. AB - When monoclonal kits are used we can no longer detect highly elevated serum concentrations of carcinoembryonic antigen in cystic fibrosis (CF) patients as we could earlier (Pediatr Res 10:223-236, 1975). Instead, we find increased concentrations of CA 19-9 or CA 195 in the CF sera. The serum levels of CA 19-9 not only reflect the pulmonary condition of CF patients but also respond well to antibiotic therapy. Several lines of evidence suggest that the elevated serum concentration of CA 19-9 is derived from sputum and corresponds with the amount of sputum in the lung. Correlations between CA 19-9 and CA 195 in random and serial specimens from both patients with CF and patients with pancreatic carcinoma suggest that all sera contain heterogeneous, Lewis blood group-related epitopes and the proportions of various epitopes are different among individual patients. When monitored on multiple tumor markers, the pattern of CF is different from that of pancreatic carcinoma although both usually show elevated CA 19-9. Our study indicates that both CA 19-9 and CA 195 can be used as sensitive markers for the early detection of exacerbation in CF patients. PMID- 1506984 TI - Sensitive enzyme immunoassay (immune complex transfer enzyme immunoassay) for (antihuman T-cell leukemia virus type I) immunoglobulin G in serum using a synthetic peptide, Ala-Cys-Env gp46(237-262), as antigen. AB - A sensitive enzyme immunoassay (immune complex transfer enzyme immunoassay) for (antihuman T-cell leukemia virus type I) IgG (anti-HTLV-I IgG) in serum using a synthetic peptide, Ala-Cys-env gp46(237-262), of HTLV-I is described. Anti-HTLV-I IgG in test serum, which had been incubated with excess of inactive beta-D galactosidase to eliminate interference by anti-beta-D-galactosidase antibodies, was reacted simultaneously with 2,4-dinitrophenyl-bovine serum albumin-Ala-Cys env gp46(237-262) conjugate and Ala-Cys-env gp46(237-262)-beta-D-galactosidase conjugate. The complex formed consisting of the three components was trapped onto polystyrene balls coated with affinity-purified (anti-2,4-dinitrophenyl group) IgG. After washing to eliminate nonspecific IgG in the test serum and excess of the beta-D-galactosidase conjugate, the complex was eluted from the polystyrene balls with epsilon N-2,4-dinitrophenyl-L-lysine and transferred to polystyrene balls coated with affinity-purified (anti-human IgG gamma-chain) IgG. beta-D galactosidase activity bound to the (anti-human IgG gamma-chain) IgG-coated polystyrene balls was assayed by fluorometry. This assay was more sensitive than other methods using HTLV-I as antigen, and most negative and positive sera were discriminated. However, some results appeared to be false positive or false negative, and the peptide, Ala-Cys-env gp46(237-262), was suggested to be useful, in combination with other peptides, for improving the reliability of serodiagnosis by separately demonstrating antibodies against as many different epitopes of HTLV-I as possible. PMID- 1506985 TI - Photosensitized oxidation of cholesterol in biological systems: reaction pathways, cytotoxic effects and defense mechanisms. AB - Cholesterol resembles other unsaturated lipids in being susceptible to peroxidative degradation when exposed to a sensitizing agent, exciting light of suitable wavelength and molecular oxygen. Selected hydroperoxides of cholesterol can be used as relatively convenient and reliable indicators of primary photochemical mechanisms, allowing a distinction to be made between free radical mediated and singlet oxygen-mediated reactions. When generated in cell membranes, hydroperoxides of cholesterol and other lipids can have deleterious effects on membrane structure and function. Such damage may be exacerbated if these photoproducts undergo one-electron reduction to oxyl radicals which in turn initiate chain peroxidation reactions. Cells can resist these effects by using a membrane-based glutathione peroxidase to catalyze the two-electron reduction and detoxification of lipid hydroperoxides. Recent advances in our understanding of cholesterol photo-oxidation from the standpoints of (a) mechanistic information, (b) cytotoxicity and (c) cytoprotection are discussed in this article. PMID- 1506986 TI - Photodynamic inactivation of retroviruses by phthalocyanines: the effects of sulphonation, metal ligand and fluoride. AB - The photodynamic inactivation of retroviruses was investigated using aluminium and zinc phthalocyanine (Pc) derivatives. The N2 retrovirus packaged in either of the two murine cell lines, Psi2 and PA317, was used as a model for enveloped viruses. AlPc derivatives were found to be more effective photodynamically for inactivation of the viruses than the corresponding ZnPc derivatives. Sulphonation of the Pc macrocycle reduced its photodynamic activity progressively for both AlPc and ZnPc. Fluoride at 5 mM during light exposure completely protected viruses against inactivation by AlPc. In the presence of F-, inactivation by the sulphonated derivatives AlPcS1 and AlPcS4 was reduced 2.5- and twofold respectively. In a biological membrane (erythrocyte ghosts), F- had no significant effect on AlPcS4-sensitized lipid peroxidation. Under similar conditions, cross-linking of spectrin monomers in ghosts is drastically inhibited (E. Ben-Hur and A. Orenstein, Int. J. Radiat. Biol., 60 (1991) 293-301). Since Pc derivatives do not inactivate non-enveloped viruses, it is hypothesized that inactivation occurs by photodynamic damage to envelope protein(s). Substitution of sulphonic acid residues reduces the binding of Pc derivatives to the envelope protein(s), thereby diminishing their photodynamic efficacy and the ability of F- to modify it. PMID- 1506987 TI - Configuration of triporphyrin ethers probed by fluorescence measurements. AB - The fluorescence spectra and lifetimes of triporphyrin ethers derived from hematoporphyrin, mesoporphyrin and protoporphyrin were examined, together with relative hydrophobicities estimated from reverse-phase high performance liquid chromatography (HPLC) elution times. The following data suggest a molecular arrangement with two of the three rings in a "folded configuration". The trimers display a greater fluorescence yield (phi f) than the corresponding diporphyrin ethers which contain only the two folded rings. The fluorescence lifetime data for the trimers are consistent with signals from both a folded ring pair (7-8 ns) and a free ring (14 ns). Reverse-phase HPLC studies indicate that the trimers are intermediate in hydrophobicity between the monomers and dimers. Preliminary data suggest that, for certain peripheral substitutions, the trimer configuration is superior to the dimer for photodynamic therapy. PMID- 1506988 TI - Riboflavin-photosensitized anaerobic modification of rat lens proteins. A correlation with age-related changes. AB - When rat lens homogenate or its soluble protein fractions are irradiated in the presence of riboflavin, a photo-adduct is obtained between this vitamin and the lens proteins. Irradiation of these proteins in the presence of riboflavin also leads to a modification in the chromatographic elution pattern with an increase in the high-molecular-weight fraction. In an aging study with rats, it was shown that the proportion of the high-molecular-weight protein fraction significantly increased with age, whereas the proportion of the low-molecular-weight protein fraction concomitantly decreased. It is postulated that aging produces an increase in the accessibility of the tryptophan residues of the lens proteins, as established by iodide fluorescence quenching experiments. PMID- 1506989 TI - Fluorescence anisotropy studies of dibucaine.HCl in micelles and bacteriorhodopsin. AB - Emission and excitation spectra for the local anesthetic drug, dibucaine.HCl in neutral and charged surfactant solutions and in bacteriorhodopsin (bR) have been investigated for lambda(ex) = 266 nm at room temperature. The total fluorescence and fluorescence anisotropy decays of the anesthetic in the same environments were also measured using a picosecond laser/streak camera system (lambda (ex = 266 nm)). The total fluorescence decay gave two components for dibucaine micellar and dibucaine bR solutions, one component in the range of 200-500 ps and the other in the range of 1200-3400 ps. Only the nanosecond timescale component was found for the dibucaine monomer surfactant solutions (1200-3000 ps), indicating that the anesthetic resides in the bulk solution. The fluorescence anisotropy decays of dibucaine in Triton X-100 and in lithium dodecyl sulfate (LDS) micelles are approximately 200 ps, which is attributed to dibucaine solubilized in the micellar environment. Dibucaine.HCl in anionic monomer solution exhibits an unusually large fluorescence anisotropy, r(t)max = 0.22 and a depolarization decay of less than 100 ps. This presumably results from a head-to-tail exciplex aggregation between the positively charged dibucaine and negatively charged dodecyl sulfate surfactant molecules. The anisotropy decay of dibucaine in bR is 300 ps. This solution was the only one which exhibited a residual fluorescence anisotropy, r(infinity) - 0.08. This implies that dibucaine is restricted in its rotational motion and suggests protein binding rather than lipid solubility. PMID- 1506990 TI - Environmental effects of ozone depletion: 1991 update. Panel Report pursuant to Article 6 of the Montreal Protocol on Substances that Deplete the Ozone Layer under the auspices of the United Nations Environment Programme. PMID- 1506991 TI - Biological clocks: mechanisms and developments. AB - Almost all organisms ranging from unicellular protists to mammals were found to show biological rhythms. Many workers have performed various kinds of experiment to understand the mechanism as well as to find the origin of the clock responsible for these rhythms. However, there is no doubt about the existence of a biologically controlled clock in almost all organisms; yet its origin and mechanism still remain a mystery. Many theories have been put forward to explain the mechanism of these biological clocks and it seems that the cell membrane may play a key role. The existence of a very high electric field of the order of 10(5) V cm-1 across the cell membrane may have some role in the mechanism of the biological clock. Of all the factors which have the effects on biological rhythms, light and temperature are found to be the most common. Also, the study of these biological clocks can help to solve the sleeping problems of international travellers and shift workers as well as to improve diagnosis, cure and prevention from diseases. PMID- 1506992 TI - In vitro phototoxicity of nifedipine: sequential induction of toxic and non-toxic photoproducts with UVA radiation. AB - Anecdotal reports suggest that the dihydropyridine calcium antagonist, nifedipine (NIF), may be phototoxic in human skin. We have studied NIF phototoxicity in vitro using UVA fluorescent tubes (Sylvania PUVA). NIF was phototoxic to Candida albicans and induced photohaemolysis both with NIF present during irradiation and with pre-irradiated drug. In V79 hamster fibroblasts, NIF (10 micrograms ml-1) was phototoxic MTT assay) 24 h after irradiation (0-112 kJ m-2); at 7.5 kJ m-2, about 70% of cells were damaged whilst at 37.5 kJ m-2, only about 45% of cells were damaged. A similar pattern was seen with pre-irradiated NIF. Absorption spectroscopy showed that the NIF absorption maximum (Amax approximately 340 nm) blue-shifted to 314 nm at low UVA doses (7.5 kJ m-2 or less) and red-shifted to 345 nm at higher doses (isosbestic point, 325 nm). Thin layer chromatography of irradiated NIF showed a single photoproduct (PP1; Amax approximately 314 nm) formed at 7.5 kJ m-2 or less which disappeared at higher UVA doses to give further photoproducts. PP1 was highly dark toxic to V79 cells (50% damage at about 5 micrograms ml-1) but PP1 pre-irradiated with UVA was non-toxic. Preliminary gas chromatography-mass spectroscopy studies suggest that PP1 is the nitroso derivative of NIF. These results indicate that NIF phototoxicity in vitro is partially mediated by initial formation of a toxic photoproduct (PP1) but, paradoxically, subsequent UVA irradiation may reduce phototoxicity. The NIF concentrations required to induce in vitro phototoxicity are much greater than therapeutic plasma levels. Unless there is skin accumulation of NIF or PP1, our in vitro results suggest that NIF may not be an important skin-photosensitizing agent in vivo. PMID- 1506993 TI - Activation of mouse macrophages by in vivo and in vitro treatment with a cyanine dye, lumin. AB - The cyanine photosensitizer, lumin, is a potent macrophage activating agent: 4 days after administration of small amounts of lumin to mice (20-40 ng mouse-1), peritoneal macrophages exhibited a greatly enhanced Fc-mediated ingestion activity; higher doses (more than 3000 ng mouse-1) did not have this effect. The in vitro photodynamic activation of macrophages in mouse peritoneal cells exposed to white fluorescent light (3 J m-2 s-1) was also studied in media containing various concentrations of lumin. A short light exposure (45 J m-2) with 10 ng lumin ml-1 produced a maximum ingestion activity of macrophages. Lumin has absorption peaks at 670 and 760 nm. Therefore we designed experiments in which peritoneal cells were exposed to a red fluorescent light (emission, 660 nm; 0.5 J m-2 s-1). In a medium containing 3 ng lumin ml-1 with 7.5 J m-2 of red light, a markedly enhanced ingestion activity of macrophages was observed. The photodynamic treatment of peritoneal macrophages alone did not stimulate phagocytic activity, but the photodynamic treatment of a mixture of non-adherent (B and T) cells and macrophages resulted in a greatly enhanced ingestion activity of macrophages. Thus non-adherent cells are required for the photodynamic activation of macrophages, implying that an activating factor is generated within the non-adherent cells and transmitted to the macrophages. This hypothesis was confirmed by the observation that co-cultivation of photodynamically treated non adherent cells with untreated macrophages resulted in a greatly enhanced ingestion capacity. PMID- 1506994 TI - Characterization of tumorous and normal tissue using a pH-sensitive fluorescence indicator (5,6-carboxyfluorescein) in vivo. AB - The pH of the interstitial fluid of malignant tumours tends to be lower than that of normal tissue and is depressed by glucose administration. This study aimed to evaluate the effectiveness of dual-wavelength fluorometry using a pH-dependent indicator (5,6-carboxyfluorescein: 5,6-CF) for the detection of tumour areas in vivo. 5,6-CF has two main characteristics: it has two wavelengths of maximum absorbance (465 and 490 nm) and its fluorescence emission (maximum, 515 nm) increases as a function of pH in the physiological pH range of 6-7.4. The experimental study was performed on 28 CDF mice bearing lymphoid leukaemia P388 grafted subcutaneously. The tissue pH values were evaluated from the ratio of the fluorescence intensities (I490/I465) on the basis of a calibration curve linking pH measurements performed within the tissue using a microelectrode and values of the fluorescence intensity ratio. The fluorescence intensity reached its maximum value 60 min after 5,6-CF and glucose administration, followed by a plateau (90 min) when the ratios remained constant at 1.79 +/- 0.05 for normal tissue and 1.35 +/- 0.04 for tumour tissue (p less than 0.005). These results were correlated with the pH measurements in accordance with the calibration curve. This study validates the relevance of dual-wavelength fluorometry using a pH dependent indicator to characterize in vivo normal and tumour tissues after glucose administration. PMID- 1506995 TI - pH dependence of fluorescence and absorbance spectra of free sulphonated aluminium phthalocyanine and its conjugate with monoclonal antibodies. AB - Water-soluble phthalocyanines and phthalocyanines linked to targeting monoclonal antibodies are considered to be one of the most promising photosensitizers in photodynamic therapy. Here the spectrum characteristics of sulphonated aluminium phthalocyanine and its protein conjugate in the pH range 1.8-12.0 in solution have been studied. The pK values are determined. PMID- 1506996 TI - Affect regulation, nicotine addiction, and smoking cessation. AB - Numerous investigators have examined the role of negative affective states and affect regulation in the initiation and development of cigarette smoking behavior, smoking cessation, and relapse prevention. Affect regulation refers to any attempt to alleviate negative mood states by means of pharmacologic-, cognitive-, behavioral- or environmental-change methods. The psychological construct/process of affect regulation is examined in relation to (1) the initiation, development, and maintenance of the cigarette smoking habit; (2) the process of quitting smoking; and (3) the long-term maintenance of smoking abstinence versus relapse. Various psychosocial factors and physiological mechanisms are explored that have been hypothesized to be links between negative mood states, nicotine addiction, and smoking cessation. Implications for smoking cessation treatment are discussed in the areas of (1) the use of pharmacologic agents, such as clonidine, in the reduction of nicotine withdrawal symptoms; (2) nicotine replacement therapy; and (3) skills-training approaches to smoking cessation and relapse prevention. PMID- 1506997 TI - Nicotine dependence and alcoholism epidemiology and treatment. AB - Nicotine dependence in alcohol-involved adults is a long-ignored treatment problem. The absence of its discussion in the literature is difficult to defend in light of medical and epidemiological data on the cost and prevalence of this dual addition. Most descriptive studies of alcohol abusers published in the past 20 years have reported tobacco use rates of at least 90%. There is a crucial need to educate treatment professionals and their clients about the additional health risks associated with joint nicotine dependence and alcoholism. Historically, certain barriers to active intervention have existed in drug abuse treatment facilities, including (1) concerns that urging clients to quit smoking might have an adverse effect on their maintenance of sobriety, (2) a tendency to minimize the strength and severity of nicotine addition, (3) a lack of informative data on how best to treat smoking in recovering alcoholics, and (4) financial issues related to marketing and insurance compensation. Recent data obtained from recovering alcoholics who have tried to quit smoking and anecdotal reports from alcoholism treatment centers that have begun addressing nicotine addiction are now challenging these barriers. Education, role modeling, environmental control, and development of staff expertise can be incorporated into standard alcoholism treatment programs to jointly treat these paired addictions. PMID- 1506998 TI - Preventing relapse in the treatment of nicotine addiction: current issues and future directions. AB - Although smoking-cessation rates have continued to increase, the vast majority of smokers who quit eventually relapse. Between 1974 and 1985, over 1.3 million smokers quit during each of those years. However, 75% to 80% of those individuals resumed smoking within six months. This article describes the dynamic phenomenon of smoking relapse within the context of cyclical episodes of smoking and quitting during an individual's lifetime. Theories of the determinants of smoking relapse are reviewed and methods designed to prevent relapse are described. Smoking relapse is discussed in terms of three aspects of tobacco addiction: (1) biological-addiction mechanisms, (2) conditioning processes, and (3) cognitive social learning factors. The major determinants of smoking relapse are reviewed, including nicotine withdrawal, stress, weight gain, social influences, conditioning factors, causal attributions, and environmental variables. A transtheoretical-developmental model is explored in the longitudinal investigation of the natural history of slips (lapses) and relapse episodes. Relapse prevention interventions are described that emphasize self-awareness, self-regulation, self-efficacy, affect regulation, social support, and lifestyle balance. Recent developments in pharmacological adjuncts to treatment are also examined. It is concluded that innovative relapse prevention methods need to be designed for hard-core smokers with histories of cessation failures, substance abuse and/or psychiatric impairment. These and other recommendations for future research on smoking relapse and relapse prevention are discussed. PMID- 1506999 TI - Marijuana and immunity. AB - Despite the fairly large literature that developed during the past 15 years or so, the effect of cannabinoids on the immune system is still unsettled. The evidence has been contradictory and is more supportive of some degree of immunosuppression only when one considers in vitro studies. These have been seriously flawed by the very high concentrations of drug used to produce immunosuppression and by the lack of comparisons with other membrane-active drugs. The closer that experimental studies have been to actual clinical situations, the less compelling has been the evidence. Although the topic was of great interest during the 1970's, as indicated by the preponderance of the references from that period, interest has waned during the present decade. This waning of interest suggests that perhaps most investigators feel that this line of inquiry will not be rewarding. The AIDS epidemic has also diverted the attention of immunologists to the far more serious problem of the truly devastating effects a retrovirus can have on a portion of the immune system. The relationship between the use of social drugs and the development of clinical manifestations of AIDS has been of some interest, however. Persons infected with the virus but not diagnosed as AIDS have been told to avoid the use of marijuana and/or alcohol. This advice may be reasonable as a general health measure, but direct evidence that heeding this warning will prevent the ultimate damage to the immune system is totally lacking. PMID- 1507000 TI - Strategies for breaking marijuana dependence. PMID- 1507001 TI - The syndrome of coca paste. PMID- 1507002 TI - Treating crack cocaine dependence: the critical role of relapse prevention. AB - In order to adequately address the treatment needs of crack cocaine dependent persons, a multidimensional approach to relapse prevention must be utilized. The value of a biopsychosocial model of crack addiction and the concept of phases of recovery in providing a rationale for the recommended approach to relapse prevention are emphasized. Research findings on the determinants of relapse for crack dependent patients and the psychosocial characteristics of the crack dependent individual justify the utility of certain relapse prevention strategies. Specifically, an approach to relapse is advocated that includes the provision of pharmacological adjuncts, psychoeducation on the multideterminants of relapse, and psychotherapy that attempts to remediate underlying psychological problems that are typically found in crack dependent patients. PMID- 1507003 TI - Anthology series. I: Smokable drugs. PMID- 1507005 TI - Changing behavior is difficult! PMID- 1507004 TI - The tobacco epidemic: lessons from history. AB - Tobacco has caused the greatest epidemic of the twentieth century, which is beginning to wane in the United States, but is still growing in much of the world. The epidemic developed as a result of innovations in the tobacco industry and larger cultural changes over the 75 years prior to the introduction of Camel cigarettes in 1913. Factors that set the stage for the epidemic include the development of flue-cured and Burley tobaccos, the mechanization of cigarette production with its consequent concentration of capital in a few companies, the safety match, efficient transportation systems, and innovative advertising. Between 1913 and 1963, the cigarette industry experienced almost unbroken growth in the United States. However, since the early 1950s, increasing evidence that cigarettes cause lung cancer and other diseases has dictated that product innovation concentrate on the appearance of safety. In the late 1960s and for a sustained period since 1973, cigarette consumption has declined in the United States, but in the developing world the epidemic curve of cigarette use is still on the upswing. As tobacco use declines in the United States, it is crucial that the production of tobacco products as well as their consumption be reduced. Otherwise, attempting to control the problem in the United States will not result in a net reduction in mortality around the world. PMID- 1507006 TI - Update on inborn errors of metabolism: primary lactic acidemia. AB - Initially thought to be rare, primary lactic acidemia is diagnosed with increasing frequency. Elevations in lactate and pyruvate are markers for a variety of metabolic blocks. Although there have been great strides made in the diagnosis and treatment of lactic acidemia, much remains to be learned. As laboratory techniques improve, clinicians will be able to make an exact enzymatic diagnosis on an increasing percentage of patients. Specific enzymatic diagnosis also will help clinicians determine inheritance patterns, recurrence risks, and methods of prenatal diagnosis. PMID- 1507007 TI - Injury prevention: a survey of clinical practice. AB - The purpose of this study was to determine what education and training pediatric nurse practitioners receive about injury prevention and control and what kinds of clinical activities PNPs perform with regard to injury prevention and control. Sixty-four members of the Greater New York Chapter of the National Association of Pediatric Nurse Associates and Practitioners were questioned. Data on demographic, professional, and practice characteristics and on education and training and clinical activities in injury prevention and control were collected. Results indicated that advice about child car restraints and automobile seat belts was routinely given by less than 30% of practitioners, information about smoke detectors was given by about 15%, and advice about firearms in the home was given by 7% or less. Implications for counseling to prevent injuries are discussed. PMID- 1507008 TI - Child and adolescent obesity: the nurse practitioner's use of the SHAPEDOWN method. AB - The prevalence of obesity in children and adolescents has increased approximately 50% in the last 20 years and now affects more than one in four young people. Although family-based approaches to the problem recently have shown weight losses maintained at 5-year and 10-year follow-up, this care is unavailable in many communities because of an insufficient availability of trained providers. Nurse practitioners are uniquely appropriate for providing child and adolescent obesity services yet appear to be underrepresented among pediatric obesity care providers. This article describes a method of preventive and therapeutic care that nurse practitioners can use in clinical practice. PMID- 1507009 TI - Counseling the high-risk adolescent. AB - Interviewing and counseling high-risk adolescents provides a challenge to nurse practitioners. The problems of poverty, substance abuse, mental illness, and low self-esteem overlay other characteristics of risk, making assessment and management of the adolescent's problems complex and difficult. Survey data, obtained in this study on adolescent risk-taking, suggest that violence, aggression, and thrill-seeking behaviors are increasingly common. The finding is supported by current national statistics on adolescents. A case study is used to show the process of gathering information on home and educational settings that can provide insight into family dysfunction and specific problem behaviors. PMID- 1507010 TI - Discouraging smoking: interventions for pediatric nurse practitioners. AB - Smoking is the most preventable cause of death in this country, and it often begins in adolescence. By discouraging the use of cigarettes, pediatric nurse practitioner and other health care professionals can significantly reduce this current and future threat to the health of the nation's children and adolescents. This article describes factors associated with adolescent smoking and interventions to prevent the initiation of smoking. PMID- 1507011 TI - Young children with anogenital warts: a growing and challenging problem for health care providers. PMID- 1507012 TI - Jealousy. PMID- 1507013 TI - Pediatric pain management (Part II). AB - This article is the second in a two-part series on pediatric pain management. It primarily contains information about the use of narcotic analgesics for pediatric patients. PMID- 1507014 TI - Sudden episode of bronchospasm. PMID- 1507015 TI - Overview of health care reform. PMID- 1507016 TI - The satellite program: a model of rural pediatric care. PMID- 1507017 TI - NAPNAP position statements. PMID- 1507018 TI - General design issues in efficacy, equivalency and superiority trials. AB - Critical discussion is offered of design issues pertinent to three categories of clinical trials: efficacy trials, in which an experimental intervention is compared to an inert control, and equivalency and superiority trials, in which an experimental intervention is compared to an active control. The issues discussed are sample-size determination and power, problems in designing and analyzing multicenter trials, broad versus concentrated sampling of patients, the need (or not) for a placebo control group in an active control trial, the possible appropriateness of crossing patients over from one regimen to another, various methods of randomization, the intention-to-treat principle in repeated measurements studies, and possible logical conflicts between inferences from superiority trials and inferences from equivalency trials. PMID- 1507019 TI - General issues in efficacy, equivalency, and superiority trials: clinical considerations. AB - The design of clinical trials aimed at treating different types of periodontal diseases must take into account the prevalence of the disease in the population and the relationship of various descriptors, which may vary from disease to disease. For screening purposes, patients should be selected with disease in the high-severity range, in order to maximize the likelihood of detecting a therapeutic effect. Subsequent trials may be designed around a more representative group of subjects. Therapies must be evaluated on the basis of actual clinical changes, rather than their effect on presumed etiologic factors. The observed changes must be of clinical as well as statistical significance. The distribution of periodontal diseases within a dentition may affect as few as one or as many as over one hundred sites. Strategies are needed to correlate events observed at sites within the dentition, i.e. tooth surface-based measurements or scores, with events that are subject-based, e.g. concentration of blood or salivary components. PMID- 1507020 TI - The effect of experimental design parameters on the determination of sample size. PMID- 1507021 TI - Logical and analytic issues in dental/oral product comparison research. AB - Possible meanings of "superiority" and "equivalence" in comparative dental studies are considered. A proposed refinement of vocabulary is introduced to precisely distinguish between these meanings. Implications for data analysis of different interpretations of "superiority" and "equivalence" are explored, as are implications for study design where design and analytic considerations are inseparable. Conceptual problems of equivalence studies are stressed. Choice of analytic unit(s), scaling of dependent variables, use of surrogate variables, and validity checking are discussed as they pertain to comparative studies. Analytic methods for correlated responses and categorized responses are briefly surveyed, particularly with reference to periodontal research. PMID- 1507022 TI - Toward strategies for the analysis of periodontal disease clinical trials. AB - We consider design, analysis and regulatory issues relating to clinical trials in periodontal disease and identify complications commonly associated with such studies. Alternative statistical procedures that can be used for the analyses of data from periodontal research are reviewed and a case study of the analysis of a Phase II periodontal disease clinical trial is provided to illustrate the use of one of these procedures. PMID- 1507023 TI - Advertising regulation at the Federal Trade Commission. PMID- 1507024 TI - Considerations in the analysis of site-specific dichotomous responses. PMID- 1507025 TI - Biological and measurement issues critical to design of gingivitis trials. AB - Chronic plaque-induced gingivitis is usually of little consequence, thus the concern about prevention and treatment must stem from the belief that preexisting gingivitis is necessary for periodontitis to develop. When clinical signs of gingivitis are present, an inflammatory infiltrate can be found upon histological evaluation. When clinical signs are absent, however, significant inflammation may still be present within the gingival tissues. Therefore, multiple clinical evaluations should be made, with special attention given to the visually inaccessible midinterdental area. The "gold standard" for evaluation of gingivitis is histological evaluation and other measurements should be evaluated against this standard. The significance of clinical severity measurements of gingivitis is not well-understood relative to onset of periodontitis; therefore, it is suggested that consideration be given to gingival evaluations based on the presence or absence of clinical signs of inflammation. Furthermore, equivalency and superiority of antigingivitis agents or devices should be predicated, at least in part, on their ability to prevent the onset of periodontitis. PMID- 1507026 TI - Some thoughts on the measurement of gingivitis. AB - The selection of a method for measurement is of critical importance in the planning of a study. Despite the great strides afforded by research of gingivitis, a "gold standard" for its measurement has yet to be clearly established. Traditional clinical indices continue to serve as "gold standards" in many investigations. There is a need for some caution and tentativity in interpreting the results of such studies. Additionally, those studies which yield data on an ordinal scale should make more use of statistical methodologies specifically geared toward the analysis of such data. PMID- 1507027 TI - Specific statistical considerations relevant to the design and analysis of gingivitis trials demonstrating product superiority or equivalence. AB - Simulation studies were conducted to address specific statistical issues which arise in the design and analysis of gingivitis studies whose principal aim is the demonstration of superiority or equivalence of one product to another. The effects of measurement scale, using differences or ratios of group means, particular statistical test produces and specific rules demonstrating superiority or equivalence were investigated. An alternative concept to equivalence--denoted "least as good"--was also defined and evaluated. For a wide class of possible distributions of gingivitis scores, characterized by specific gamma distributions, the student-t test applied to means of subject GI gingivitis scores proved to be the most powerful of the test produces considered, having statistical properties quite similar to the randomization or permutation test procedure. Transformations of subject GI mean gingivitis scores did not produce an advantage in demonstrating either superiority or equivalence, and in some cases made it more difficult. Little difference was observed in test results when using the difference in group means as compared with using the ratio of group means for demonstrating either equivalence or superiority. The clinically significant rule produced the lowest false-positive rates for products slightly better than the active control, and similar false-positive and -negative rates as the statistically significant rule for products clearly superior to the active control. Demonstration of product equivalence will require more subjects per group than demonstrating product superiority, the size of this difference being a function of the definition of superiority that is accepted. Showing that the 90% confidence interval for 100*R is completely contained within the [90%, 110%] interval is the preferred method of demonstrating equivalence today, although much more research needs to be done to improve methods for demonstrating product equivalence. The "least as good" alternative to "equivalence" makes it easier to demonstrate "equivalence" for products slightly better than the active control product, but both experience great difficulty in demonstrating equivalence for test products not quite as good as the active control. PMID- 1507029 TI - Some aspects of efficient experimental design and analysis in periodontal trials. PMID- 1507028 TI - Design issues specific to studies of periodontitis. AB - Guidelines for clinical trials demonstrating equivalence or superiority for treatments for periodontitis are badly needed because of the great variety of drugs, agents, and devices now being developed. This paper focuses on three design issues. These are primary outcome variables and their measurement, disease active vs disease-inactive sites and patients, and study duration. Determinants for selection of outcome variables include the biologic events to be observed, changes that are specific for periodontitis, and methods chosen to detect those changes. The primary outcome variables specific for periodontitis and appropriate for use in clinical trials are periodontal attachment level and alveolar bone status. Improved methods for measurement of both with excellent accuracy and reproducibility are now becoming available. Studies performed on untreated patients over the past decade demonstrate clearly that disease-active and disease inactive pockets exist, at any given point in time most are inactive, disease progression is episodic and in most patients infrequent, and a rather small portion of the population--possibly around 5%--are unusually susceptible to rapid disease progression. These observations need to be taken into account in enrolling subjects into periodontitis clinical trials. Conducting a prestudy to identify actively diseased sites and susceptible subjects, or screening to enrich the proportion of active sites, is recommended. Determination of study duration is a very complex issue. It is related to the length of time required for maximal change and stabilization to occur in the biological events to be observed, the outcome variable(s) used to detect change, and the nature of the therapeutic interventions to be studied. No single duration is applicable to all periodontitis clinical trials. Large gaps in our knowledge about the design of periodontitis trials still exist, and additional research is needed. PMID- 1507030 TI - Periodontal sites or patients as the experimental unit. PMID- 1507031 TI - Considerations for the interpretation of findings from single and multiple studies of periodontal conditions. AB - This paper reviews considerations involved in the interpretation of results of individual periodontal clinical trials and the synthesis of findings of multiple studies. The purpose of each study must be considered, particularly whether it is an epidemiological investigation, prevention trial or therapeutic clinical trial. The definition of clear end-points, whether they be hygiene end-points associated with calculus and plaque or disease end-points that measure extent of gingivitis and periodontitis, is essential. Other statistical considerations include the following: adequate sample size, balanced design, use of covariates, issues of the appropriate sampling unit, and proper statistical analysis. Statistical issues that must be considered include the types of tests of hypotheses, use of multiple comparison procedures when more than two groups are involved, corrections for multiple testing and precise estimation of parameters with corresponding confidence intervals. When comparing across clinical trials, three sources of heterogeneity that must be considered are: treatments, diseases, and target populations. The technique of meta-analysis is described for the statistical interpretation of data arising from several trials. A meta-analysis is conducted for six dental clinical trials that evaluated a triclosan/copolymer formulation for the reduction of plaque, calculus or gingivitis. Results indicate that the first five studies, which were reported simultaneously, showed a common effect, i.e., that the formulation successfully reduced either plaque or calculus. When the sixth study, reported at a different time, was added to the analysis, the collection of studies did not satisfy the homogeneity assumption necessary for estimating a common effect size. This illustrates the importance of testing for homogeneity before pooling possibly dissimilar studies. PMID- 1507032 TI - Issues in the evaluation of clinical trials of periodontitis: a clinical perspective. AB - The goals of clinical trials designed to establish claims for equivalency or superiority of treatment for periodontitis must be clearly stated and defined in terms of measurable and meaningful response variables. It is suggested that these clinical trials use designs that compare new treatment methods to basic periodontal therapy which consists of thorough scaling and root planing, oral hygiene instruction, and regular maintenance care. The primary response variable should be clinical attachment level. It is important to document changes in probing depth since this is a meaningful measure to many clinicians. Gingival inflammation and bleeding should be used as secondary response variables because these are not necessarily indicative of progressive periodontal destruction. Radiographic measures of disease may be useful as primary response variables if safe, reproducible and valid methods of measuring change are utilized. Microbiological monitoring should be a secondary response variable because of numerous questions concerning sampling methodology, quantitative expression of data, and meaningful interpretation in terms of relevance to disease activity. The length of periodontitis trials should be set at a minimum of 9 months if claims of superiority or equivalency are made compared to basic periodontal therapy. Calibration trials should be included and measurement error should be expressed in terms that are meaningful to the clinician while retaining statistical validity. Statistical methods for determining change should take into account site and subject heterogeneity, bursts of change and gradual change over time. It is important that statistical techniques be used that detect change as early as possible and that appropriate consideration be given to the clinical implications of the type, magnitude and duration of change in outcome variables. PMID- 1507033 TI - Results from studies of periodontal disease at the University of Florida. PMID- 1507034 TI - Some comments on meta-analysis: discussion of "issues specific to evaluation of studies of periodontitis". PMID- 1507035 TI - Issues of individual study analysis and synthesis of studies specific to evaluation of studies of periodontitis. PMID- 1507036 TI - Effect of a social cognitive intervention on oral health status, behavior reports, and cognitions. AB - An intervention designed to test the influence of cognitive restructuring on protective oral health behaviors was conducted with 108 patients with mild to moderate gingivitis. Subjects in the experimental group viewed slides of active, mobile bacteria taken from their mouths on 5 occasions: before and after prophylaxis and at 3 appointments, one month apart. A specially trained hygienist discussed with these participants the process of periodontal disease, the role of bacteria, and self-efficacy (self-control) for oral hygiene self-care. Both experimental and control group subjects received instruction in oral self-care procedures. Assessments of oral health using Loe and Silness' plaque and gingival indices (PI and GI) were taken throughout the study and at 3- and 6-month follow up visits. Self-efficacy, oral hygiene intentions, attitudes, and values comprised the set of cognition variables. Plaque and gingival indices mean differences between groups approached significance at visit 6. Analyses were also performed using percent of gingival surfaces scored at "0" (no visible bleeding on probing). A trend occurred for group differences in percent "0" scores at visit 6, with the experimental group maintaining higher percent zeros (better health) at this 3-month follow-up. At visit 7 (9-month follow-up), PI and GI differences disappeared. No significant differences were found between groups for oral health cognitions or behavior reports over time. The data suggest that the cognitive-behavioral intervention produced a delayed relapse in protective oral self-care behaviors, and by extension, oral health status. Such a delay could be clinically relevant in promoting adherence to oral hygiene behavior between professional visits. PMID- 1507037 TI - The effects of chlorhexidine on the attachment and growth of cultured human periodontal cells. AB - The purpose of this investigation was to evaluate the effects of chlorhexidine (CHX) on the attachment and growth of human gingival fibroblasts and periodontal ligament cells using an in vitro system where periodontal cells were grown on root surfaces treated previously with CHX. Our results indicate that the attachment of periodontal cells onto root surfaces was not adversely affected when roots were treated for 15 minutes with up to 0.12% CHX. However, cell attachment and morphology were adversely altered with prior 0.2 to 2.0% CHX treatment. The cells appeared round and retracted from roots treated with 0.2% CHX. With 2% CHX treatment, the cells exhibited a foamy appearance in which most of the cytoplasm seemed to have been extracted from the cells. Although 0.12% CHX treatment did not adversely affect the attachment of periodontal cells onto roots, direct exposure to as little as 0.01% CHX caused a 90% reduction in 3H thymidine incorporation by cultured gingival fibroblasts. We conclude that although 0.12% CHX did not inhibit the attachment of cultured periodontal cells to pretreated roots, direct exposure of cells to much lower concentrations of CHX (0.0025 to 0.01%) caused a dose-dependent inhibition of growth. PMID- 1507038 TI - A comparative clinical study of the safety and efficacy of three toothbrushes. AB - This single (examiner) blind, randomized, 4-week study compared the safety and efficacy of a new electric toothbrush (experimental) regarding plaque removal and reducing gingivitis with two other brushes, an electric brush (control electric) and a manual toothbrush (control hand). Ninety-six subjects with 1) a minimum of 15 suitable teeth in acceptable occlusion; 2) a minimum gingivitis score of 0.9; and 3) a minimum plaque score of 1.8 were entered into the study. The subjects were randomly assigned to one of 3 groups: a control hand group (31 subjects), an experimental group (32 subjects), and a control electric group (33 subjects). Device use instructions were given according to the manufacturer's recommendations. Two examiners separately determined either gingival scores or plaque scores at baseline and 4 weeks. In regard to gingivitis, use of all 3 brushes for the study period showed statistically significant improvements in gingivitis scores (P values less than 0.01) within each of the 3 groups. Between group analyses of covariance showed that of the 3 groups, the control hand group improvement was better than both the experimental and the control electric groups (P less than 0.05). When interproximal gingivitis scores were analyzed separately, similar improvements were noted. Regarding effectiveness of plaque removal during a single brushing event at the initial and final visits, each of the 3 brushes was effective in reducing plaque for every tooth surface scored (P values less than 0.01). However, between group analyses of covariances showed that the experimental group was better than the other two (P less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1507039 TI - Rinsing with delmopinol 0.2% and chlorhexidine 0.2%: short-term effect on salivary microbiology, plaque, and gingivitis. AB - The aim of this short-term study was to compare the effect of delmopinol HCl 0.2% and chlorhexidine digluconate 0.2% rinses on the development of dental plaque, the healing of experimental gingivitis, and the salivary microbiology. As part of a larger study protocol, 45 healthy males enrolled in an oral hygiene program to upgrade their oral health. For this portion of the study, participants had their teeth professionally cleaned on day 0. The participants then abstained from standard mechanical oral hygiene procedures, but applied a placebo solution twice daily for 2 weeks. At the end of this period the subjects received a second professional cleaning and were then assigned to 2 treatment groups: Group 1 rinsed with 10 ml of delmopinol HCl 0.2% and Group 2 rinsed with 10 ml of chlorhexidine digluconate 0.2% for 1 minute twice daily for the next 2 weeks and continued to refrain from mechanical oral hygiene procedures. At the end of the placebo and active treatment periods 1) saliva samples were taken and cultivated on a series of media; 2) the degree of gingivitis was assessed with gingival crevicular fluid (GCF) and gingivitis index (GI); and 3) the plaque index was assessed and the stainable buccal plaque extension was analyzed planimetrically. No changes in the salivary microbiological counts were detected for the subjects rinsing with delmopinol. Subjects rinsing with chlorhexidine showed significant reductions of anaerobes, aerobes, and S. mutans in saliva. The amounts of GCF and GI were reduced largely to the same extent in both treatment groups. Mean plaque extension was reduced by 52% after delmopinol and 88% after chlorhexidine rinsing.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1507040 TI - The effects of the Nd:YAG laser on in vitro fibroblast attachment to endotoxin treated root surfaces. AB - The purpose of this study was to evaluate the effects of the Nd:YAG laser on in vitro fibroblast attachment to endotoxin-treated root surfaces and to describe any laser-induced cementum surface alterations. Thirty 4 mm x 4 mm cementum segments were obtained from unerupted third molars. The treatment groups were as follows: 1) control, healthy root segment; 2) non-lased, endotoxin treated; and 3) lased, endotoxin treated. The endotoxin treated roots were soaked in E. coli 055:B5 lipopolysaccharide (556 EU/ml) for 72 hours. The lased, endotoxin-treated root segments were treated with a Nd:YAG laser using a 320 microns contact optic fiber handpiece with an energy setting of 80 mJ at 10 pulses per second for one minute. The root segments were subsequently placed in fibroblast culture dishes for 40 hours and then prepared for scanning electron microscopy (SEM) observation. SEM examination revealed two different types of attachment: flat and round. Flat cells represented firmly attached cells due to well-defined points of attachment and numerous lamellapodia. Round cells possessed few attachment processes and were, therefore, considered poorly attached. The lased, endotoxin treated root segments had significantly decreased numbers of flat fibroblasts versus the control and non-lased, endotoxin-treated root segments. The absence of flat fibroblasts in the laser treated root segments was a consistent finding. The non-lased, endotoxin-treated root segments had significantly increased numbers of round fibroblasts versus the control and lased, endotoxin treated groups. The lased root segments exhibited surface alterations which included charring, crater formation, cementum meltdown, and tracking.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1507041 TI - Chemical characterization of lased root surfaces using Fourier transform infrared photoacoustic spectroscopy. AB - Recently lasers have been recommended as an alternative or adjunctive therapy in the control and treatment of periodontally diseased root surfaces. The purpose of this in vitro investigation was to characterize the chemical structure of lased root surfaces using Fourier transform infrared photoacoustic spectroscopy (FTIR/PAS). Cementum samples, 6 mm x 2 mm, were cut from the root surface of extracted non-carious, unerupted human molars. The experimental samples were lased with a Nd:YAG laser at an average energy of 80 mJ at 10 pulses per second. Total lasing time ranged from 1 minute 45 seconds to 4 minutes. A non-lased cementum sample served as the control. All spectra were recorded from 4000 to 400 cm-1 using the photoacoustic cell attachment on an Analect RFX-65 FTIR Spectrometer. Photoacoustic FTIR spectra of lased cementum samples showed a decrease in the protein/mineral ratio in comparison to the control. Breakdown of protein at the root surface potentially contributed to an ammonium band at 2010 cm-1. The decreased protein/mineral ratio and the potential surface contamination with protein by-products, may ultimately affect cell reattachment at the cementum surface. PMID- 1507042 TI - The effect of Nd:YAG laser exposure on root surfaces when used as an adjunct to root planing: an in vitro study. AB - The purpose of this study was to evaluate the effects of Nd:YAG laser treatment on root surfaces in vitro when used alone or in combination with conventional scaling and root planing. The study population consisted of 18 unerupted third molars, each with a 3 mm diameter treatment site outlined on the root surface. Three specimens were randomly assigned to each of 6 different treatment groups: 1) untreated control; 2) root planed only; 3) laser treated only using 1.25 W of energy; 4) laser treated only using 1.50 W of energy; 5) laser treated with 1.25 W of energy followed by root planing; and 6) laser treated with 1.50 W of energy followed by root planing. Following their respective treatment, all specimens were prepared for evaluation by scanning electron microscopy. Specimens from Group 2, root planed only, exhibited a smear layer of scale-like texture with parallel instrument tracks resulting from curet use. Specimens treated by laser only, Groups 3 and 4, featured various surface changes not observed in controls such as charring and carbonization of the cementum surface, randomly distributed pitting and crater formation, and melting of the root mineral phase with subsequent resolidification as porous globules. Those specimens treated by laser followed by root planing, Groups 5 and 6, exhibited surface characteristics similar to those noted in Group 2 specimens. Further, there were areas of exposed dentinal tubules resulting from a "peeling" of the cementum layer. The results of this in vitro study suggest that laser use during root preparation, even at relatively low energy levels, will result in physical changes to the root surface.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1507043 TI - Pneumoparotitis associated with the use of an air-powder prophylaxis unit. AB - A case reporting barotrauma to the parotid gland secondarily to the use of an air powder prophylaxis unit is presented. Air pressure associated with these units usually exceeds that for air/driven turbines or air/water dental syringes, yet the reported incidence of iatrogenic trauma is very low. Improper angulation in the use of these instruments may result in serious sequellae. Differential diagnosis and physical examination following trauma to the parotid is discussed. PMID- 1507044 TI - Recurrent peripheral odontogenic fibroma of the attached gingiva: a case report. AB - Peripheral odontogenic fibroma is an uncommon, benign, unencapsulated, exophytic gingival mass of fibrous connective tissue covered with a surface epithelium. Odontogenic epithelium and mineralized material may be found in the mass. A case is reported of a lesion that recurred in the attached gingiva following initial excision. Differential diagnosis of exophytic gingival lesions and post-operative management are also discussed. PMID- 1507045 TI - Computerized methodology for detection of alveolar crestal bone loss from serial intraoral radiographs. AB - The aim of this study was to develop a computerized measurement system for analysis of unstandardized serial radiographic images. A new approach for estimating the error associated with the determination of alveolar crest loss is described. The study shows that a difference of 0.87 mm in cemento-enamel junction-crest measurement between unstandardized serial radiographs taken within accepted clinic routine is required for a significant loss in crestal bone height. The ability to detect with significance a difference of less than 1 mm in crestal bone height makes the appropriate use of traditional bite-wing radiographs a useful diagnostic tool for the assessment of periodontal maintenance. PMID- 1507046 TI - Retained "hopeless" teeth: lack of effect periodontally-treated teeth have on the proximal periodontium of adjacent teeth 8-years later. AB - We previously reported the lack of effect periodontally-treated teeth prognosed "hopeless" and retained for 3.4 +/- 1.5 years have on the proximal periodontium of adjacent teeth. We now report our findings for the same group of subjects following 8.4 +/- 0.7 years of "hopeless" tooth retention. Of the 17 "hopeless" and adjacent teeth originally measured in 17 subjects, 14 of the subjects were still available for re-evaluation. Measures used to assess the periodontium of proximal surfaces of adjacent teeth included pocket depths (PD), radiographic alveolar bone level (R-BL), and periodontal ligament space width (W-PL). Treatment for the subjects consisted of surgical therapy (N = 15) and scaling and root planing (N = 2). Of the 14 subjects re-examined, 2 were eliminated due to loss of adjacent tooth reference points and 2 due to extraction of the "hopeless" tooth (N = 10). Differences in measurements (i.e., nonadjacent to "hopeless" tooth value minus adjacent to "hopeless" tooth value) were analyzed using a repeated measures ANOVA. There were no significant differences for PD (P = 0.20), R-BL (P = 0.29), or W-PL (P = 0.16). These data confirm our original findings that retained periodontally "hopeless" teeth do not significantly affect the proximal periodontium of adjacent teeth following therapy. PMID- 1507047 TI - A histomorphologic study of the effects of periodontal inflammation on the maxillary sinus mucosa. AB - Twenty blocks of human jaws obtained at autopsy and containing maxillary molar teeth with the contiguous maxillary sinus intact were prepared utilizing conventional histopathologic techniques and were studied by light microscopy. The purpose of this investigation was to confirm earlier clinical reports suggesting a close association between human periodontitis and maxillary sinus thickening and to morphologically document the nature of the sinus changes. Seventeen of 20 jaw specimens demonstrated moderate to advanced periodontal destruction with pervasive extension of the inflammatory infiltrate through the alveolar process beyond the apices of the teeth and extending to the region of the antrum. Of the 20 histologic specimens, 10 showed extensive thickening of the sinus membrane, 9 had moderate hyperplastic changes, and only 1 specimen demonstrated a normal appearing sinus. Pathologic changes in the sinus membrane included inflammatory cell infiltration, edema, fibrosis of the tunica propria, mucous-serous gland proliferation, interstitial pseudo-cyst formation, polyp formation, hyalinization of the connective tissue lining, thrombosis of blood vessels, and metaplastic and degenerative changes in the epithelial lining. This study, based on histopathologic changes, suggests an apparent direct relationship between moderate and severe periodontitis of the maxillary molar teeth and pathologic changes resulting in thickening of the maxillary sinus mucosa. PMID- 1507048 TI - Association between detection of oral Actinobacillus actinomycetemcomitans and radiographic bone loss in teenagers. A 4-year longitudinal study. AB - The aim of the present study was to assess a possible association between radiographic bone loss and presence of Actinobacillus actinomycetemcomitans on the site and subject level over time. Forty-six teenagers with registered radiographic bone loss and 8 controls participated in the study, which began in 1984. In 1986 and 1988 new sets of bite-wing radiographs were obtained and examined for bone loss. Subgingival plaque was sampled from both diseased and contralateral healthy sites in the same individual. Only 15 of the 46 originally diseased sites persisted with bone loss in 1986, and 60% of these sites harbored A. actinomycetemcomitans. Of the 31 "healed" sites, 29% contained A. actinomycetemcomitans. The difference was statistically significant at P less than 0.05. Six of the contralateral healthy sites had developed bone loss during these 2 years and 50% of them contained A. actinomycetemcomitans, while 35% of the remaining contralateral sites harbored A. actinomycetemcomitans. The difference was not statistically significant (P greater than 0.05). The difference between patients with and without persistent bone loss regarding presence of A. actinomycetemcomitans was statistically significant in 1986; however, none of the observed differences were statistically significant in 1988. A. actinomycetemcomitans was found 2 to 3 times more frequently in patients with radiographic bone loss at all examinations than in "healthy" subjects. Detection of A. actinomycetemcomitans on the site level appeared to be a poor predictor of future radiographic bone loss. PMID- 1507049 TI - Distribution of natural killer cells in periodontal diseases: an immunohistochemical study. AB - We studied the distribution and incidence of natural killer (NK) cells in gingiva affected with adult periodontitis (AP) and rapidly progressive periodontitis (RP) with immunohistochemical methods using antibodies Leu-7 and Leu-11b. The incidence of Leu-7 positive cells revealed no significant difference among mild AP, severe AP, and RP. On the other hand, Leu-11b positive cells were frequently found in severe AP and RP. The accumulation of NK cells reacting with Leu-11b in the infiltrated connective tissue was greater in severe forms of periodontal disease (severe AP and RP) than in mild AP. These results suggest that Leu-11b positive NK cells may play a role in the destruction of tissues in periodontal diseases. PMID- 1507050 TI - Multi-level statistical models in studies of periodontal diseases. AB - Periodontal data typically have a hierarchical structure, with sites grouped within individuals, and individuals grouped within communities. Also, the occasion may be regarded as another level since the acquired knowledge indicates that periodontal disease activity may vary over time. Conventional statistical tests are based on unilevel analysis of data. However, this approach to statistical analysis is often inconvenient in periodontal research because of the variation in the outcome variables between the various levels in the hierarchy. Lately there have been important developments in the statistical theory which have made available powerful statistical techniques for analyzing multilevel or hierarchical data. This report describes a new approach for analyzing periodontal data and uses an illustrative example to build a model which explains part of the variability in the response variable. The results from this analysis are then compared to results from an earlier report which uses unilevel methods and the findings discussed. The present multilevel approach has several advantages over unilevel methods, mainly due to its statistical validity and efficiency. Further, it permits the incorporation of explanatory variables measured at the site and the subject levels, and those which vary across the time points. Multilevel analyses have a promising potential and are expected to have a significant impact on periodontal research. PMID- 1507051 TI - Treatment of an osseous lesion associated with a severe palato-radicular groove: a case report. AB - This is a case report that describes the management of a severe periodontal defect associated with a palato-radicular (palato-gingival) groove affecting the maxillary right lateral incisor of a 50 year-old male. The patient presented with pain, gingival swelling, and a 10 mm periodontal pocket on the distopalatal aspect of the right maxillary lateral incisor. The defect was initially treated by scaling and root planing. Several days later a flap was elevated, the osseous defect was debrided, and odontoplasty was performed to eliminate the groove. The root surface was treated with citric acid for 3 minutes, the osseous defect was filled with non-porous hydroxyapatite, a periodontal membrane was placed, and the flap was readapted to the tooth. Postoperative care included systemic (minocycline) and local (chlorhexidine) antimicrobial therapy. The membrane was removed 6 weeks postoperatively and 14 months postoperatively the gingiva appeared healthy; radiographs suggested substantial resolution of the osseous defect and about 7 mm of probing attachment gain was recorded. Further studies are necessary to determine which of the several modes of therapy used to treat this lesion are necessary for success. PMID- 1507052 TI - Tuberous sclerosis with gingival overgrowth. AB - A case of tuberous sclerosis with gingival overgrowth is presented. A brief literature review and diagnostic criteria of tuberous sclerosis are discussed. The patient had a full-mouth gingivectomy with frequent post-operative maintenance visits. After 6 months, the overgrowth in conjunction with the tuberous sclerosis returned. PMID- 1507053 TI - Multiple focal pigmented lesions in the maxillary tuberosity and hard palate: a unique display of intraoral junctional nevi. AB - The pigmented conditions located in the oral cavity have a diverse genesis ranging from vascular lesions to exogenous and endogenous pigmentations. In this report we have documented the unusual occurrence of multiple intraoral junctional nevi in a patient. A review of the patient's past dental records revealed that 2 of these lesions were first noticed 8 years earlier; however, no efforts were made to identify the nature of the pigmentations. Removal of 4 lesions and subsequent histopathological analysis revealed the presence of junctional nevi. This case illustrates the importance of a thorough clinical and histological work up when dealing with pigmented lesions in the oral cavity. The excision of all suspected oral nevi is warranted because they cannot be clinically differentiated from other pigmented lesions, including oral melanoma. In addition, the potential of junctional nevi to undergo malignant transformation in the oral cavity is undetermined. PMID- 1507054 TI - The importance of timing in melatonin administration in a blind man. AB - An 18-year-old blind man suffered from chronic sleep disturbances associated with daytime fatigue and excessive daytime somnolence. After two unsuccessful treatment regimens with 5 mg and 10 mg melatonin administered at bedtime (2200 2230), a third regimen of 5 mg melatonin administered at 2000 for 3 weeks resulted in a successful resolution of his sleep disturbances. We suggest that the efficacy of melatonin in ameliorating sleep disturbances because of alterations in circadian rhythmicity may be dependent on the time of administration. PMID- 1507055 TI - Circadian rhythms of plasma melatonin in the ruin lizard Podarcis sicula: effects of pinealectomy. AB - Plasma melatonin was measured in lizards (Podarcis sicula) at six different times of day under conditions of constant temperature and darkness. Intact animals showed a circadian rhythm of melatonin with a peak in the subjective night of 207 pg/ml (median) and a trough during the subjective day that was below the minimum detection level of the assay (50 pg/ml). Pinealectomy abolished the circadian rhythm of plasma melatonin; median levels were near or below the minimum detection level at all times sampled. The data suggest that the pineal is the only source of rhythmic blood-borne melatonin in Podarcis sicula, and are consistent with the hypothesis that changes in the free-running period of the locomotor rhythm induced by pinealectomy in this species are due to withdrawal of rhythmic melatonin from the blood. PMID- 1507056 TI - Administration of melatonin into the mediobasal hypothalamus as a continuous or intermittent signal affects the secretion of follicle stimulating hormone and prolactin in the ram. AB - The biological effects of administering melatonin into the mediobasal hypothalamus (MBH) was documented in adult Soay rams using two delivery systems: (1) microimplants in the MBH delivering melatonin continuously and (2) microdialysis probes in the MBH delivering melatonin intermittently as a daily timed infusion. The experimental protocol was to precondition rams to long days (LD 16:8) for 10 to 12 weeks, and then introduce the exogenous source of melatonin by implantation or infusion. Sixteen rams were divided equally into four treatment groups: (a) microimplants in the MBH, (b) microdialysis probes in the MBH, (c) empty microimplants in the MBH to act as sham-operated controls, and (d) no surgery to act as unoperated controls. The microimplants consisted of 22 gauge stainless steel cannulae with melatonin fused inside the tip and were placed bilaterally in the brain for 14 weeks. These implants had previously been shown to release melatonin at a relatively constant rate when incubated in buffered saline at 37 degrees C (3.42 +/- 0.42 micrograms/24 hr, mean +/- SEM, 1 10 weeks) and to produce a localised concentration of melatonin when implanted in the brain (localised to within 1 mm of the center of the implant). The microdialysis probes were also 22-gauge cannulae with a 3 mm membrane (Biotech). They were placed bilaterally into the MBH, connected to two portable syringe drivers secured to a backpack. Melatonin was infused daily for 10 hr (estimated delivery: 0.5 microgram/hr) starting in the mid-light phase to produce a long duration intermittent melatonin signal. Technical problems limited the period of infusions to 8-10 weeks with minor interruptions. Animals from all groups were maintained on long days, and the observations extended for a period of 28 weeks. The melatonin implants placed in the MBH induced a premature increase in the blood concentrations of FSH and growth of the testes. This treatment also induced a marked decrease in the plasma concentrations of prolactin and the earlier development of the long winter pelage. These changes were reversed after the end of treatment with a decline in the plasma concentrations of FSH and regression of the testes, and an increase in the concentrations of prolactin and moult of the winter pelage. Daily infusions of melatonin from the microdialysis probes in the MBH produced qualitatively similar, but less marked responses. The overall results illustrate that the administration of melatonin into the MBH, either continuously or intermittently, to extend the duration of the daily melatonin signal, induces multiple short-day responses.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1507057 TI - A culturally biased perspective. PMID- 1507058 TI - A center of nursing excellence: supporting the professional practice environment. AB - The Center of Nursing Excellence is a unique, multifaceted program that promotes the professional practice environment. The Center provides programs and services in six areas: career planning and development, nursing practice review, research and grants support, scholarly affairs, nursing outreach, and nursing resources. The Center serves as a resource to nurses at St. Louis Children's Hospital and in the nursing community at large. PMID- 1507059 TI - Teenagers' knowledge of the acquired immunodeficiency syndrome and associated risk behaviors. AB - Adolescents are now recognized as being at high risk for contracting the human immunodeficiency virus (HIV), the presumed cause of acquired immunodeficiency syndrome (AIDS). This article reports the findings of a survey that examined AIDS knowledge, risk behaviors, and informational sources for AIDS in a group of suburban New Jersey high school students (N = 152). This group had knowledge of HIV and its transmission, but results indicated that students also participated in behaviors considered "risky" for the transmission of HIV. These behaviors included unprotected sexual intercourse (40% of sexually active males) and sexual intercourse with multiple partners over a period of time (23% of sexually active males). PMID- 1507060 TI - Failure to thrive: a parent-infant interaction perspective. AB - The purpose of this study was to prospectively study inpatients admitted for failure to thrive during their first year of life. Twelve infants with failure to thrive were studied and compared with 17 healthy controls. Mothers and infants with nonorganic failure to thrive scored lower on the Nursing Child Assessment Feeding Scale, reported more change in their lives, and less social support. The need for further research is discussed and suggestions for beginning level interventions are made. PMID- 1507061 TI - Children's knowledge of internal anatomy: conceptual orientation and review of research. AB - Children's understanding of health and illness is influenced by their knowledge of internal anatomy and physiological functioning. This article provides a comprehensive review of studies of children's knowledge of internal anatomy, one component of internal body image. Consistencies, controversies, and methodological issues that emerge across the studies are discussed. A conceptual framework for the development of children's internal body image is presented. The framework posits relationships between cognitive development, health status, knowledge of internal body image, and understanding of physiological functioning. Future studies are needed to test and refine the conceptual framework and to develop interventions to facilitate children's internal body image. PMID- 1507062 TI - Respite care services to caretakers of chronically ill children in California. AB - Caring for chronically ill and/or technology-dependent children at home can be emotionally, physically, psychologically, and financially exhausting for the caregiver. Caregivers require temporary relief from the burden of day-to-day care of these children. Respite care offers the opportunity for this relief. A study was conducted to survey the availability of respite care for chronically ill and technology-dependent children in California. Survey findings from 45 agencies indicated that 38% provided respite care for chronically ill and/or technology dependent children. Fifty percent of agencies provided care for less than 10 chronically ill and/or technology-dependent children per year. Major problems associated with provision of respite services were inadequate reimbursement and insufficient request for services. PMID- 1507063 TI - Infant stimulation during hospitalization. AB - Stimulation is essential to the development of infants and children. They are developing skills related to gross motor, fine motor-adaptive, language, and personal-social functioning. Hospitalization can disrupt the developmental process for infants, even those without pre-existing developmental delays, if intervention is not provided. Hospitalized infants are often subjected to an overabundance of meaningless stimulation or understimulation. Nursing needs to insure provision of meaningful stimulation to help alleviate the effects of hospitalization. Parents and/or significant others need to be included whenever possible. A suggested infant stimulation program for hospitalized infants is presented. Practicality for the pediatric clinician facilitates easy intervention. PMID- 1507064 TI - Characteristics of caregivers that promote children's development in day care. AB - Most available evidence on day care suggests that characteristics of the caregiver are the key components of high-quality child care. Yet, this fact is rarely appreciated by parents or policy makers. As primary health care providers, nurses can educate parents, caregivers, and policy-makers concerning the broad array of day-care features, including caregiver characteristics that should be considered. This article provides a review of the research on characteristics of caregivers that are found in high-quality day care and describes how these factors facilitate optimal development in young children. From the research findings, implications for nursing practice at the family, community, and national levels are identified. PMID- 1507065 TI - Clinician-friendly research: not an oxymoron. PMID- 1507066 TI - Make your votes count! PMID- 1507067 TI - Event recorders: a new technology for home cardiorespiratory monitors. PMID- 1507068 TI - Community education programs specifically for children. PMID- 1507069 TI - Pediatric nursing in the United Kingdom. AB - Child health matters remain low on the government agenda, and present reforms of the NHS are overtly concerned with financial aspects rather than the quality of care. Pediatric nurses must therefore become more assertive and pro-active in their role as advocates for children and their families. However, pediatric nurses are extremely fortunate in the UK because they have (a) a nurse education system that has always recognized that the nursing needs of children are different to those of adults, (b) the opportunity to work with medical and voluntary organizations committed to improving children's health, and (c) a professional organization that is not only large and powerful, but since 1984 has been committed to advancing the art and science of pediatric nursing. It employs a full-time adviser to assist its members and publishes the only pediatric nursing journal. Pediatric nurses have assisted in advancing the art and science of pediatric nursing with caring for children and their families in a holistic fashion, with families supported and participating in their child's care. But there are still many opportunities to improve the quality of health care to children and their families. Quality caring is what children and their families want and deserve, but is not as easy to measure as quantity care. At a time when in so many countries, health service managers concentrate on quantity, pediatric nurses must use every opportunity to shape the health policy of their nation for the benefit of children. We all live in interesting times and it would be interesting to see what we make of them on behalf of children. PMID- 1507070 TI - On the special status of "ego threats". AB - This article comments on a recent article by Heatherton, Herman, and Polivy (1991) in which they suggest that ego threats are a prerequisite to affectively induced disinhibition of food intake in restrained eaters and current dieters. In contrast, the present review suggests that mood induction procedures that involve no apparent threat (e.g., viewing a frightening film) can also prompt disinhibition in restrained eaters. Thus, any mood induction procedure that does not directly physically threaten the S may disinhibit restrained eaters. It is concluded that recommendations to focus future research on ego threats are premature and may serve to obscure the mechanisms by which changes in affective state influence food intake in dieters. PMID- 1507071 TI - An assessment of cadmium toxicity on cytochrome P-450 and flavin monooxygenase mediated metabolic pathways of dimethylaniline in male rabbits. AB - Cadmium is an environmental pollutant and its effect on the in vitro metabolism of N,N-dimethylaniline (DMA) using male rabbits was investigated. Activities of cytochrome P-450 and FMO-dependent monooxygenases were studied using hepatic microsomes. Following CdCl2 (i.p.) administration (6 mg/kg/day for 6 days), both DMA-N-oxidation and DMA-N-demethylation decreased by 86%. The effects of CdCl2 on the phenobarbitone (PB)-induced form of P-450 were also studied. Intraperitoneal pretreatment of rabbits with PB (5 mg/kg/day for 5 days) increased N demethylation by 82%, while N-oxidation decreased by 49%. Both reactions decreased significantly on additional treatment with CdCl2. Promethazine (5 mg/kg/day for 5 days) did not produce any change in the activities of either enzyme. The enzymes remained unaffected by CdCl2 treatment in promethazine pretreated animals thus confirming its role as a hepatoprotective agent. PMID- 1507072 TI - The etiological role of diet, smoking, and drinking habits of patients with esophageal carcinoma in Turkey. AB - Esophageal cancer has a known high incidence in areas adjacent to the Caspian Sea and in northeastern Turkey. This study compares the incidence of esophageal cancer in Bursa (northwestern Turkey) with an age-matched control population. Factors associated with esophageal cancer and significantly at variance with controls include: age over 70, low income, smoking more than one pack of cigarettes per day, and low vegetable and fresh fruit intake. PMID- 1507073 TI - The influence of soil components and drinking water on the appearance of cancer: a review. AB - The author reviews the relationships of soil and reused water with the occurrence of cancer. The effect of the soil composition on the emergence of geocancerologic diseases such as cancer of the stomach, esophagus, urinary tract, breast, bronchus, pleura, and bone is analyzed. The study also reviews geocancerologic diseases linked with the use of recycled waste water. PMID- 1507074 TI - Chemical inactivation of aflatoxins in peanut protein ingredients. AB - Aflatoxin contamination of peanuts has posed a threat to the peanut industry in utilizing peanuts as a source of a low-cost protein ingredient for food and feed. Although the best approach to containing the aflatoxin problem in peanuts is prevention, it appears that chemical inactivation of aflatoxin in contaminated raw material provides the best means to salvaging the contaminated material. Several chemical reagents have been investigated for their efficacy in destroying aflatoxins present in raw peanuts and defatted peanut meal. Using certain oxidizing agents such as NaOCl, H2O2, and benzoyl peroxide; bases such as ammonia, methylamine, and calcium hydroxide; and aldehydes such as formaldehyde, contaminated raw peanuts or defatted peanut meal have been demonstrated to yield peanut meals, protein isolates, and concentrates having trace amounts or nondetectable levels of aflatoxins. Processing conditions for inactivating aflatoxins using these chemicals were investigated. The chemical treatments had little effect on the physiochemical properties of the detoxified protein product. The advantages and disadvantages of using these chemicals for inactivation of aflatoxins are discussed. PMID- 1507075 TI - Alterations in the hematological profile in rat following whole body gamma radiation with and without venoruton pretreatment. AB - The radioprotective effect of venoruton [O-(beta-hydroxyethyl)-rutoside] has been assessed in the hematological profile of Swiss albino male rats subjected to a single dose of 300 rads whole body gamma radiation. The results showed that the severity of the radiation-induced abnormalities in the red and white blood cells is significantly lessened by venoruton administered prior to radiation exposure. PMID- 1507076 TI - Hematological lesions in rat following heavy alcohol ingestion. AB - Hematological fluctuations following large alcohol oral administration (2 mL per animal per day) in rats were monitored at intervals ranging from 10 to 22 weeks and the findings were compared to those in control animals that were fed sucrose isocalorically. Following alcohol ingestion, there was a significant decrease in the total blood cellularity at all treatment intervals. A fall in the erythrocyte count per millimeter3 was accompanied by decreased hematocrit values and hemoglobin levels in the alcohol-treated animals. On the other hand, the MCV and MCH values were significantly elevated after alcohol ingestion. Despite overall leukopenia observed after alcohol ingestion, there was a significant increase in the absolute neutrophil count. The absolute lymphocyte count, however, fell significantly in the alcohol-treated animals. Eosinophils and basophils were not significantly altered by alcohol toxicity. PMID- 1507077 TI - Treatment of Morton's neuroma as a nerve compression. The role for neurolysis. AB - The almost universal surgical approach for the treatment of Morton's metatarsalgia is to resect the neuroma through a dorsal incision. Considering that the mechanism for the metatarsalgia is chronic repetitive compression of the common plantar digital nerve between the metatarsal heads, this report explores the use of neurolysis in five patients with 11 involved nerves. In surgery, the intermetatarsal ligament is divided, intrinsic fibrosis is released, and the epineurium is opened. The mean follow-up period is 33 months. Complete pain relief was achieved in four of the five patients, with the fifth patient, 13 years after a crush injury to the foot, achieving good pain relief. All five patients resumed their usual jobs and athletic activities. One patient wears sneakers instead of regular shoes. The patient with the crush injury wears custom made shoes. PMID- 1507078 TI - On some arthropathies apparently related to a lesion of the brain or spinal cord, by Dr J.-M. Charcot. January 1868. PMID- 1507079 TI - Effect of insole material on force and plantar pressures during walking. AB - Twelve subjects between the ages of 24 and 35 years walked barefoot over a pressure platform with the following insole materials placed directly on top of the platform: 1) PPT, 2) Spenco, and 3) Viscolas. Maximum vertical force, vertical force-time integral as well as maximum plantar pressure data were collected for the rearfoot, midfoot, and forefoot regions. The results were not significant for maximum vertical force and vertical force-time integral among the three insole materials when compared to barefoot-only walking. There was, however, a significant reduction in forefoot maximum plantar pressure among the three materials compared to barefoot-only walking. In the rearfoot region, a reduction in maximum plantar pressure was seen only with PPT and Spenco. PMID- 1507080 TI - Postoperative physical therapy for podiatric surgery. AB - The authors discuss several rehabilitation protocols for different surgical procedures on the foot. These are designed to be used as a reference for the podiatrist and therapist. In addition, various modalities are highlighted to familiarize the practitioner with their uses. Physical therapy can aid in decreasing the recovery period from foot surgery, which is particularly advantageous for the athlete. PMID- 1507081 TI - Idiopathic sural neuroma. A case report. PMID- 1507082 TI - Synovial osteochondromatosis. A brief review. AB - An unusual clinical finding is presented with a brief review of the literature. Synovial osteochondromatosis is typically a benign process involving metaplasia of the synovial intima and the formation of cartilaginous nodules that may eventually become ossified. Synovial osteochondromatosis should always be considered as a differential diagnosis whenever a patient presents with pain, swelling, and loss of function at or around a joint. Chondrosarcoma has been misdiagnosed, leading to radical and unnecessary amputation, because synovial osteochondromatosis has not been considered. Alternatively, synovial osteochondromatosis may degenerate to or be associated with a malignant process. When radiographs or more sophisticated investigative procedures, such as magnetic resonance imaging, fail to provide a conclusive answer, histologic findings provide the definitive diagnosis. PMID- 1507083 TI - Hydrocortisone phonophoresis. A literature review. PMID- 1507084 TI - An overview of cold injuries. PMID- 1507085 TI - Nodular variety of keloid simulating neoplasia. PMID- 1507087 TI - Cast metal resin-bonded dental restorations: effect on the resin-to-metal bond of storage conditions before cementation. AB - Cast metal resin-bonded restorations are often stored in the laboratory or dental practice/office before they are fitted in the mouth. This study investigated the effect of the storage conditions of such restorations on the tensile bond strength of a resin cement. Sixty cylinders were cast in nickel-chromium alloy (Wiron 88). Their bonding surfaces were sandblasted, cleaned ultrasonically in distilled water, and air dried. Groups of 10 cylinders were stored for 10 days in an office environment as follows: in an open container, in a sealed polyethylene bag, in a plastic pot, in distilled water, or in acetone. A control group was used immediately for bonding. Each cylinder was bonded with a thin film of resin (Panavia Ex) to a freshly prepared disk of the same alloy. After 24 hours in water at 37 degrees C, the assembly was loaded under tension to failure. The results indicated that storage in an open container should be avoided and that restorations can best be protected by storage in distilled water. PMID- 1507086 TI - Bond versus rebond strengths of three luting agents for resin-bonded fixed partial dentures. AB - Recently, new luting materials have been claimed to have adhesion to metal and tooth structure. This study determined if rebonding the specimens affected their tensile bond strength. Ten samples each of Rexillium III metal cylinders (12 x 6.3 mm) were bonded and rebonded with Comspan Panavia and Super-bond materials. The film thickness was controlled with a micrometer device at 20 microns. The samples were stored for 24 hours in deionized water at 37 degrees C and were then thermocycled for 24 hours and tested for tensile failure on an Instron testing machine. A stereomicroscope was used to determine adhesive/cohesive failure. The results showed a significant difference at p greater than 0.01 in tensile bond strengths (bond versus rebond strength) for all three luting agents. Most of the failures were adhesive in nature. PMID- 1507088 TI - Bonding fixed prosthodontic composite resin and precious metal alloys with the use of a vinyl-thiol primer and an adhesive opaque resin. AB - Adhesive bonding of a light-cured fixed prosthodontic composite resin joined to silver- and gold-based alloys was investigated with the use of a metal primer and an adhesive opaque resin. The primer contained an adhesive bonding promoter for precious alloys, 6- (4-vinylbenzyl-n-propyl) amino-1, 3, 5-triazine-2, 4-dithiol (VBATDT). The cast metal specimens were alumina-blasted and primed with VBATDT acetone solution. A self-curable 4-META/MMA-TBB opaque resin was used to bond the primed metals and a light-cured composite resin. Prepared specimens were thermocycled in water and bond strengths were determined. The shear bond strengths after 100,000 thermocycles (4 degrees C to 60 degrees C for 1 minute) were 28.4 MPa for Ag-Pd-Cu-Au alloy and 20.8 MPa for type III gold alloy. This simple method may be used to bond silver or gold alloy and light-activated fixed prosthodontic composite resin. PMID- 1507089 TI - Clinical evaluation of a composite resin system with a dentin bonding agent for restoration of permanent posterior teeth: a 3-year study. AB - This study evaluated the clinical performance of a visible light-cured small particle bimodally filled hybrid condensable composite resin system that included a dentin bonding agent compared with an amalgam alloy in class II restorations of permanent teeth. A total of 108 restorations were placed in 34 patients. Fifty three composite resin and 55 amalgam restorations were inserted. Each restoration was evaluated immediately after placement and then on an annual basis for a 3 year period using the Public Health Service (PHS) criteria. In addition, the Moffa-Lugassy scale was used to measure the loss of material on the occlusal surface of these materials. One hundred percent of the resin and amalgam restorations were evaluated, measured, and reasons for replacement were recorded over the 3-year period. There was no significant difference (p greater than 0.05) in the clinical performance of the composite resin and the amalgam when evaluated by the PHS criteria. Analyses of wear at each of the three annual recall periods did not reveal any significant difference (p greater than 0.05) between the two restorative materials when measured by the Moffa-Lugassy scale. PMID- 1507090 TI - Effect of laser-etch on bond strengths of glass ionomers. AB - This study evaluated the bond strength between glass ionomer cements and laser etched dentin. Extracted human molars were sectioned sagittally, creating a flat surface. Samples were shear tested on an Instron testing machine, and mean bond strengths were recorded; statistical analyses indicated no significant differences between the Ketac cements. The bond strengths of both Ketac cements were significantly decreased when applied to laser-etched dentin, but bond strengths of Fuji-II were substantially elevated compared with the control values. PMID- 1507091 TI - Tensile bond strength of repaired amalgam. AB - This study evaluated the tensile strength of repaired high-copper amalgams and analyzed the different treatments of the amalgam interface prior to repair. One hundred specimens were divided into 10 groups: group 1 was left intact and was considered as the control group. In groups 2 through 8, the specimens were sectioned into halves after 10 days and were reconstructed with new amalgam. Groups 9 and 10 were condensed with time intervals of 15 minutes and all specimens were subjected to tensile loads in a Universal Testing Machine. The tensile strengths at the junction between old and new amalgam ranged between 50% to 79% of those of the control group and verified that the same type of amalgam and uncontaminated interfaces had higher strengths. The results also suggested that if an amalgam repair is anticipated, additional retention is critical to the longevity of the restoration. PMID- 1507092 TI - Tooth contacts in eccentric mandibular positions and facial morphology. AB - Correlations between facial morphology and tooth contacts in excursive mandibular positions were studied in 75 men aged 20 to 33 years. The morphology of the dentition was verified on dental casts and the face was measured by use of roentgen cephalometry. No correlation was observed between facial morphology and the number of tooth contacts in the retruded position; however, wide dental arches and jaws displayed many contacts on protrusion. Numerous contacts on the functional side in group function were noted in individuals with a facial morphology associated with distal occlusion, such as Angle class II, division 1. Wide dental arches were associated with multiple functional-side contacts whereas tooth contacts on the nonfunctional side were related to the inclination of the mandible. A "long-face" morphology was related to contacts on the nonfunctional side. There was a negative correlation between the extent of the overbite (vertical overlap) and the number of tooth contacts on the nonfunctional side. PMID- 1507093 TI - Pulpal evaluation of teeth restored with fixed prostheses. AB - The literature demonstrates that each of the elements of crown fabrication involves possible and probable insult to the pulpal tissues of the tooth. Preparation of the tooth can result in pulpal inflammation or even burn lesions. The impression technique can result in reduction of the odontoblastic layer caused by drying of the dentin. Temporary coverage of the preparation involves the use of self-curing resins and temporary cements, both of which can irritate the pulp. The final restoration is attached with cements that are often implicated in pulpal irritation. Dental caries and the procedures necessary to remove it and restore the tooth before preparation for a fixed prosthesis can injure the pulp. This study was done to evaluate the effects of complete coverage fixed prosthetic restorations on the dental pulp. A recall letter was mailed to 1221 patients who had received a fixed partial denture or single crown during the years 1984-1988. One hundred thirty patients were examined. Each tooth was evaluated for pulpal health, periodontal integrity, and clinical acceptability of the restoration. Of the 603 teeth examined, 166 had undergone root canal therapy before placement of the restoration, leaving 437 that were crowned while vital. Of these, 25 (5.7%) were in need of root canal therapy or had undergone root canal therapy after cementation of the fixed prosthesis. PMID- 1507094 TI - Temperature extremes produced orally by hot and cold liquids. AB - Thermocycling in vitro is a common way of testing dental materials to aid in establishing suitability for in vivo use. There is no standard temperature range for dental material thermocycling. This research attempts to establish an appropriate temperature range by measuring extremes of temperature achieved orally in human volunteer subjects. By using an intraoral digital thermometer probe, 13 human subjects were observed as they drank very hot and cold liquids. The temperature extremes produced intraorally were measured and adjusted for possible error. The results of this study suggest that a range of 0 degrees to 67 degrees C may be appropriate for dental material thermocycling. PMID- 1507095 TI - A comparative study of the fit and retention of interocclusal splints constructed from heat-cured and autopolymerized polymethylmethacrylate. AB - Fifty-three subjects each had a single Michigan splint constructed of either heat cured or autopolymerized polymethylmethacrylate. The choice of material was decided randomly. A blind assessment for fit and retention was used on a three point scale. Fit and retention were apparently unaffected by the material used. Thirteen percent of splints were unsatisfactory for clinical use (poor fit or retention) and this was also independent of material. A small number of splints contained structural faults (voids, porosity, or cracks) that may shorten the clinical life of these restorations; 9 of 12 such faults occurred in the autopolymerized group. Previous research has shown that conventional heat-cured polymethyl-methacrylate has superior properties compared with autopolymerized resin. In the absence of differences in accuracy of fit or retention, a heat cured material is therefore advised where splints are intended for long-term clinical use. PMID- 1507096 TI - Comparison of the intercondylar distance and the interfacial width as used with the electronic pantograph. AB - The electronic pantograph (Pantronic) records mandibular movements and computes the articulator settings. The Pantronic pantograph does not determine the intercondylar distance but approximates it from the interfacial width at the condyles. An average distance of 12.5 mm is subtracted from each side to determine the intercondylar distance. This study recorded 45 patients' articulator intercondylar distances that had been set from a mechanical pantograph and they were compared with the Pantronic's approximation. The difference between the interfacial width and the actual intercondylar distance was 15.1 mm on the right side and 14.9 mm on the left side. A numerical value of 15.0 mm was statistically superior to the Pantronic's 12.5 mm in estimating the average distance between the intercondylar distance and the surface of the skin at the condyle. No statistically significant difference was found between the differences of interfacial width and intercondylar distance values for men and women (p greater than 0.05). The mean intercondylar distance was 56.5 mm on the right side and 56.7 mm on the left side. A statistically significant difference was found between the mean intercondylar distances of men and women (p less than 0.05). PMID- 1507097 TI - A reliable index for correct positioning of precision attachments into an existing overdenture. AB - Limited space over abutment teeth may make incorporation of a precision attachment system within an existing overdenture technique sensitive. A special diagnostic index can be made to depict the available space within the prosthesis over the abutment teeth. This index is critical to determine the feasibility of attachment incorporation, as well as the selection and correct positioning of an appropriate attachment system. A method to improve predictability for precision attachment incorporation into an existing overdenture is described. PMID- 1507098 TI - Computer-aided evaluation of occlusal load in complete dentures. AB - A computerized diagnostic system was tested for its capability to evaluate the occlusal equilibrium of complete dentures. Its electronic sensor foil was calibrated to intraorally compute a load index for the left and right sides of the denture. The index is calculated by the measured force and number of occlusal contacts. Perfect equilibrium is given by a ratio of load left-to-load right of 1:1. Centric occlusion of complete dentures was examined before and after remounting. A good correlation between load index and the occlusal relationship on the articulator could be observed. The system appears to be suitable for verifying the need for occlusal adjustment. However, improvements concerning the hardware and software are necessary. PMID- 1507099 TI - A technique for making an esthetic maxillary complete denture surgical stent. AB - A technique for making an esthetic complete denture as a surgical stent to be used in conjunction with hydroxyapatite augmentation surgery of the maxillary arch is presented. The technique involves the use of an articulator, a remount jig, and duplication of a surgically prepared cast. PMID- 1507100 TI - A socioeconomic comparison of patients receiving prostheses in a two-tier delivery system. AB - It has been theorized that the legalization of providers of denture care other than dentists would make dentures more affordable to and therefore more often obtained by individuals of lower socioeconomic status. The delivery of dental prostheses by nondentists (denturists) has been legalized in Arizona, Colorado, Idaho, Maine, Montana, and Oregon. This study compares the socioeconomic and utilization patterns of two groups of patients receiving prostheses: (1) those whose prosthetic services were provided by dentists and (2) those whose services were provided by denturists. The sample included 135 participants; 31 individuals with 54 prostheses made by denturists and 104 individuals with 165 prostheses made by dentists. Application of the chi-square test and the Hollingshead Two Factor Index of Social Position revealed no statistically significant correlation, (p less than 0.05) between the provider-based groups and standard socioeconomic variables. The history and pattern of choice of provider as well as level of satisfaction were also remarkable for the similarity displayed by the two groups. It would appear that the two groups are actually one homogeneous group served by two levels of providers. PMID- 1507101 TI - Sonographic measurement versus mapping for determination of residual ridge width. AB - To achieve long-term success of dental implants, evaluation of the dimensions of the resorbing alveolar process must be accurate because an implant should be surrounded by at least 1 mm of bone. Estimating the thickness of bone is more difficult because the mucosal contour can mask the actual dimension of the residual ridge. With ultrasound, it is possible to analyze and visualize the diameter of maxillary or mandibular residual ridges. Data obtained from ultrasound measurement of residual ridges were compared with the data from ridge mapping with the Wilson bone caliper and the Spoerlein caliper. The ultrasound measurement produced nearly the same data at all measurement points as ridge mapping. Ultrasound also provides exact information about the location of the mental foramen and the maxillary sinus. By using all three methods the initial stage of implant treatment can be planned. PMID- 1507102 TI - Determining the force absorption quotient for restorative materials used in implant occlusal surfaces. AB - It has been hypothesized that the type of material used to form the occlusal surface of restorations retained by dental implants may impart a "dampening effect" to the bone-implant interface. This study compared the force transmitted to human bone by gold, porcelain, and resin occlusal surfaces in a simulated implant occlusal rehabilitation. A Branemark self-tapping implant was placed in a human cadaver mandible with a stacked three element strain gauge cemented to the lingual cortical plate. An Instron testing machine was used to apply an axial force, through a peanut sample, to a restoration that contained interchangeable occlusal surfaces. Applied force was divided by recorded microstrain at the bone strain gauge junction to derive a calculated ratio, or force absorption quotient. No statistically significant difference of the force absorption quotient between the occlusal surfaces of gold, porcelain, and resin was observed. PMID- 1507103 TI - Fabrication of bolus compensators used in the treatment of irregular tissue surfaces in radiation therapy. AB - Radiation treatment involving irregular surfaces of facial topography often causes difficulties for the radiation oncologists. The isodose curves normally used become skewed, thereby making treatment planning more complex. A simple and useful technique is presented describing the use of dental materials to make a bolus compensator to aid in radiation therapy of nonplanar surfaces. This technique will allow the radiation oncologist to treat these patients in a most efficient manner. The materials needed are readily available to the dentist and are easily handled. PMID- 1507104 TI - An acrylic resin core for processing silicone facial prostheses. AB - A technique is presented for making an acrylic resin core for processing silicone facial prostheses. This technique ensures a durable core that can be used to make multiple prostheses. The core resists fungal growth during storage and creates a smooth, easily cleanable internal surface for a facial prosthesis. The core also permits a controllable thickness and therefore a lighter prosthesis. PMID- 1507105 TI - Stabilization of an interim obturator prosthesis using a denture duplicator. AB - Concomitant radiotherapy and chemotherapy given within weeks after major surgical procedures may require that an interim obturator prosthesis be worn for extended periods of time. Interim reline materials used in fabricating the interim obturator prosthesis may become rough and difficult to clean. With a Lang denture duplicator it is possible to easily convert an interim obturator prosthesis to an all acrylic resin prosthesis. A technique is described for this procedure. PMID- 1507106 TI - A mold technique for orbital prostheses. AB - This technique describes a method for making maxillofacial prostheses with tissue undercuts that allows trial closure for esthetic characterization. The finish line is placed on the external eyelid to facilitate final trimming of the prosthesis. PMID- 1507107 TI - Oral commissure expansion prosthesis. AB - An expansion prosthesis to stretch commissures and fibrotic muscles is often essential for patients recovering from head and neck trauma or burns. The prosthesis is easily made in one appointment using Triad resin and a 7 mm expansion screw. Depending on the frequency of use, varying degrees of opening of the jaws can be obtained. The prosthesis is inexpensive to make and can easily be modified as needed. It is convenient for use because the patient controls the pressure that is applied by the prosthesis. PMID- 1507108 TI - Microwave-cured tracheostoma vents. AB - This article describes a technique of making custom flexible and combined flexible/rigid tracheostoma vents. The combined flexible rigid tracheostoma vent provides a flexible material that is nonirritating in the peristomial region and maintains a patent tracheostoma by the rigidity of the hard acrylic resin section. The flexible tracheostoma vent can be easily inserted and is more comfortable than the rigid commercially available tracheostomy tube. The use of microwave-cured materials permits fabrication during a single visit. The steps involved in the fabrication of the tracheostoma vents are simple and require no elaborate laboratory equipment. PMID- 1507109 TI - Influence of tooth contact on the path of condylar movements. AB - The correlation between condylar inclination and tooth guidance was tested by comparison of recordings of condylar movement in right and left parasagittal planes during lateral excursion, opening, and protrusive movements in 13 subjects with temporomandibular joint (TMJ) clicks and 15 subjects without TMJ clicks. The characteristic tracing of mandibular movements at the condyle with tooth-guided versus non-tooth-guided conditions were investigated by use of a computerized Axiograph graph. The generated tracings of each subject were graphed and analyzed to calculate the horizontal condylar inclinations as related to the axis orbital reference plane. Information from a standardized questionnaire provided evidence of a definite correlation between the presence of TMJ clicking and a specific prior medical event (tonsillectomy). The data from computerized tracings of all subjects revealed no significant difference (p 0.05) in the mean angles of condylar guidance at any of the millimeter intervals examined regardless of whether the craniomandibular contact was an articulation of natural teeth or an articulation of maxillary natural teeth against a tray clutch. These results do not suggest that dynamic interarch tooth guidance or the change in vertical dimension reflect a significant alteration in the recordings of condylar guidance in clicking or nonclicking groups. PMID- 1507110 TI - Edentulous position of the temporomandibular joint. AB - Two bilateral Schuller's position radiographs were made of 10 edentulous patients with complete dentures. In one radiograph, the complete dentures were in place in centric occlusion. For the other radiograph, the complete dentures were removed and the maxillary and mandibular residual ridges approximated as closely as possible. This position is referred to as the edentulous position of the temporomandibular joint (TMJ). Findings indicate that in the edentulous position the average size of the upper and posterior TMJ spaces and the distance from the center of the condyle to the center of the glenoid fossa on the Y axis of the TMJ are smaller than measurements in the intercuspal position. The size of the anterior space and the distance between the two centers on the X axis are larger in the endentulous position. Because vertical dimension is reduced in the endentulous position, the mentum is in a superior and protrusive position. The study indicates that when the maxillary and mandibular residual ridges are approximate there is a pathologic position of the TMJ and the mandible caused by the loss of all teeth. The study shows that the condyle has the potential to move backward and upward excessively. As a result of the study, the concept of the edentulous position of TMJ is introduced. This concept is important in determining the proper position of the condyle in the glenoid fossa and the correct vertical and horizontal jaw relationship of an edentulous patient when complete dentures are made. PMID- 1507111 TI - Effects of intense chewing on some parameters of masticatory function. AB - This study recorded the influence of 30 minutes of intense chewing on the masticatory function in 17 healthy subjects. Functional recordings of mandibular movements and velocity, measurements of masticatory efficiency, maximal occlusal force, and occlusal force endurance time were performed before and after functional stimulation and finally in a 2- to 5-day follow-up registration. After intense chewing, a substantially decreased masticatory cycle and occlusal level phase duration were recorded. No major mandibular displacements or changes in velocity were recorded. Masticatory efficiency and maximal occlusal force in the incisal region diminished after 30 minutes of intense chewing. Occlusal force endurance time was also lowered after intense chewing. The measurements were close to their original values at the follow-up. Intense chewing had various short-term effects on masticatory function, including a significant reduction of masticatory efficiency, maximal occlusal force, occlusal force endurance, and masticatory cycle duration. PMID- 1507112 TI - Comparison of an anatomic versus physiologic method of posterior tooth placement for complete dentures. AB - Many authorities agree that artificial teeth should occupy the same positions as their natural predecessors to minimize interference with muscle function. A survey revealed that 59.2% of dental schools taught students to arrange mandibular posterior teeth over the crest of the ridge. That method was compared with a physiologic method of tooth placement. Fifty subjects, 33 women and 17 men, participated in the study. Arranging the mandibular posterior teeth with the central groove over the crest of the ridge resulted in a mean reduction of 2.72 mm in arch width. In the female subjects, the mean reduction in arch width of 3.06 mm was 56% greater than the mean of 1.96 mm recorded for men. PMID- 1507113 TI - Working cast verification. AB - The procedure described can allow correlation of clinical recordings of the patient's centric position with articulated working casts, thereby potentially eliminating most of th occlusal adjustments required when the restoration is seated in the mouth. PMID- 1507114 TI - The transverse strengths of three denture base resins reinforced with polyethylene fibers. AB - This investigation compared the transverse strengths of three denture base resins with and without polyethylene reinforcement fibers. These fibers were incorporated in 10 specimens each of a high-impact strength resin, a rapid heat polymerized resin, and a light-activated resin. Each specimen was broken on an Instron universal testing machine using a three-point load after processing and air drying. The values obtained were then compared with values previously recorded for the same type of specimens without incorporated fibers. Only the light-activated denture base resin specimens exhibited a significantly higher mean transverse strength after polyethylene fiber reinforcement. PMID- 1507115 TI - Shear strength of laboratory-processed composite resins bonded to a silane-coated nickel-chromium-beryllium alloy. AB - The shear bond strengths of three commercial laboratory curing composite resin veneers bonded to a nickel-chromium-beryllium alloy treated with the Silicoater system were evaluated. Two light-cured resins and one heat- and pressure-cured resin were evaluated. No statistically significant difference in bond strengths among the three resins was found. Microscopic analysis of the fracture surfaces indicated that all failures were complex and cohesive in nature within the resin and composite. On the basis of the shear bond strengths measured, any of the composite resin veneers tested appear to be clinically acceptable. PMID- 1507116 TI - Management of implant malalignment precluding transfer coping placement. AB - Two techniques have been described whereby an impressin can be made when malaligned osseointegrated implant abutments preclude the use of conventional transfer copings. PMID- 1507117 TI - Minimizing cross-contamination from dental pumice. PMID- 1507118 TI - Cyanoacrylate accelerator for die preparation. PMID- 1507119 TI - Improvement in an articulator's clutch fabrication. PMID- 1507120 TI - Improvements in an articulator clutch design and registration. PMID- 1507121 TI - Control of water coolant in the maxillectomy patient. PMID- 1507122 TI - Marginal accuracy and geometry of cast titanium copings. AB - The biocompatibility of titanium with human tissue is well established; its potential as an alternate metal for crown restorations has yet to be fully investigated. This study measured the geometry and accuracy of coping margins cast in Ti, 99.5% chemically pure. Twenty castings with 45-degree facial and 90 degree palatal margins were made by indirect technique with a commercial system using recommended procedures. They were then cemented with ZnPO4 cement. The coping and die assemblies were embedded in resin, sectioned longitudinally, and measured with a microscope at x50 power. Casting shrinkage was characteristic, particularly along the horizontal axis in the plane of the shoulder. Although horizontal linear shrinkage of 45-degree margins was greater than that for the 90 degree form, the surface of marginal discrepancy was greatest with the 90-degree configuration. PMID- 1507124 TI - Thermal response to multiple use of a twist drill. AB - The objective of the present investigation was to determine whether injurious thermal changes occur in the pulp chamber if a twist drill is used 10 times, and to find whether there is a correlation between temperature rise and distance between a drilled channel and the pulp chamber. Twenty caries-free, human, premolar teeth were randomly distributed to two dentists. With a new 2 mm twist drill, each dentist prepared 10 pinholes (one hole per tooth). Intrapulpal temperature change during the drilling procedure was recorded. The data were statistically analyzed by the Spearman rank order correlation coefficient. The results showed that twist drills should not be used for more than five pinholes (p less than 0.001). The distance between the pin channel and the pulp chamber does not influence heat generation in the pulp chamber. PMID- 1507123 TI - Adhesion of resin to casting alloys. AB - The bond strength of a composite resin bonded to various dental casting alloys with three adhesive systems--Silicoater, Panavia, and Superbond C&B--was investigated. The metal surfaces were treated solely with aluminum oxide blasting before application of the adhesive. Thermal cycling caused a reduction in bond strength for all combinations of the adhesive systems and alloys, but the Silicoater system recorded the greatest bond strength. The 4-META system was equivalent to Panavia system in bond strengths to most metals and exhibited greater strength with others. PMID- 1507125 TI - A 3-year postoperative clinical evaluation of posts and cores beneath existing crowns. AB - Fabrication of posts and cores for fixed partial denture (FPD) and removable partial denture (RPD) abutment restorations is common in dentistry. The biocompatibility of various post and core techniques with the restorations was clinically evaluated according to location and function. In this study, 154 post and core constructions for 150 patients were observed for a 3-year period to determine if the function of the original restorations remained unsatisfactory. The following techniques were included: (1) screw post and light-curing composite resins, (2) cemented post with parallel sides and light-curing composite resins, and (3) a cast and core technique. Seventeen of the 154 restorations failed; four failures were attributed to root fractures, three to radicular caries, and five to crown dislodgement, while five failures were from detachment of the post and core from the root. The statistical analysis revealed that only the factor "type of abutment" (RPDs and FPDs) had some effect on the failure of the restorations. PMID- 1507126 TI - The dentin-root complex: anatomic and biologic considerations in restoring endodontically treated teeth. AB - The restoration of endodontically treated teeth has been the focus of considerable controversy and empiricism. Time-tested methods have been highly successful in some respects, but failures are still apparent. The inherent causes of failure are rarely evaluated and the limitations of specific restorative systems are seldom identified. Regardless of the system, there should be a thorough understanding of the anatomy and biology of the dentin and root supporting the restoration on the part of the practitioner, because both endodontic and restorative procedures alter the hard tissues. PMID- 1507127 TI - Anterior mandibular subapical osteotomy: a useful treatment for patients with severely worn mandibular anterior teeth. AB - Rehabilitation of patients with severe dental wear is a complex diagnostic and restorative problem. As wear occurs, space for restorative materials is lost, and unique treatment techniques are needed to provide good esthetics and function. Use of orthognathic surgery to reposition mandibular anterior teeth and supporting alveolar bone can create a more ideal environment for restorative procedures. PMID- 1507128 TI - The effect of slot preparation length on the transverse strength of slot-retained restorations. AB - An in vitro study was conducted (1) to compare fracture strength of amalgam restorations retained with retentive slots of different lengths when stressed with a transverse force, (2) to determine if beveling the slot preparation resulted in an increase in fracture resistance to a transverse force, and (3) to evaluate the incidence of unrestorable tooth fracture as it relates to slot preparation length. Six groups of 10 specimens were prepared with slots of increasing length, with each specimen receiving four slots of equal length. Slot preparations in group 6 were beveled. Results showed that shorter slot preparations provided statistically equal amounts of resistance to a transverse force as did the longer preparations. Beveling the slot preparation did not significantly increase fracture strength. Specimens restored with longer slot preparations failed unrestorably more often than restorations retained with shorter slot preparations. PMID- 1507129 TI - Seating and retention of complete crowns with a new adhesive resin cement. AB - The retentive property of cast gold complete crowns cemented with an adhesive resin cement (Panavia Ex) was compared with retention of crowns cemented with zinc phosphate cement (Flecks) and the conventional resin cement (Comspan). The effect of these agents on seating of crowns also was evaluated. Panavia cement exhibited the highest retentive strength, with values almost twice those obtained with zinc phosphate cement. However, the difference in mean retention values of crowns cemented with Comspan cement or with zinc phosphate cement was not statistically significant. Both resin cements used in this study provided better seating of crowns than did zinc phosphate cement. PMID- 1507131 TI - An impression technique to make a new master cast for an existing removable partial denture. AB - When the master cast for a removable partial denture is lost and a well-fitting framework remains, it may be necessary to replace the master cast. A two-step impression procedure is described that combines the altered-cast technique and the use of a modified disposable tray. Finger pressure is maintained on the major connector throughout the making of both impressions, to prevent framework movement and loss of contact with prepared rest seats. PMID- 1507130 TI - The cantilever fixed partial denture--a literature review. AB - The cantilever fixed partial denture (FPD) is a restoration with one or more abutments at one end and unsupported at the other end. Forces transmitted through the cantilevered pontics can cause tilting and rotational movements of the abutments. In a cross-arch unilateral cantilever FPD, the distal cantilevered unit is subjected to comparatively less force than the contralateral posterior abutment. The unilateral lack of terminal abutments causes lateral bending forces activate peripheral inhibitory feedback reactions from the periodontal and/or temporomandibular mechanoreceptors. The greatest strain in distal cantilevered FPDs is recorded mesial to the most distal retainer because most fractures occur in this location. To improve the prognosis of the FPD cantilever, the number of abutments should be increased and the number of pontics decreased. The abutment teeth need long roots and acceptable alveolar support. Prepared abutments require adequate length and parallel axial walls. An equilibrated and harmonious occlusion is necessary, as well as exemplary oral hygiene. A cantilevered FPD with adequate periodontal support can replace any tooth in the dental arch, but is especially useful as an alternative to a removable partial denture. The cantilevered FPD requires at least two abutment teeth. The only documented exception permitting a single abutment is the replacement of a maxillary lateral incisor with the canine as an abutment. An alternative to the cantilevered FPD is the osseointegrated implant. As osseointegrated implants become more popular, the need for the tooth-supported cantilevered FPD may decline, but it will remain an alternative treatment modality. PMID- 1507132 TI - Reliability of a facebow transfer procedure. AB - The three-dimensional orientation of a maxillary cast mounting from a simulated kinematic facebow transfer was evaluated in multiple trials among three operators on a single subject. The anterior and posterior anatomic facial reference points were marked on the subject. Each operator performed a separate series of trials to reset the anterior facebow component, the two posterior facebow components, and a control series with no resetting of any facebow components relative to the subject. The x, y, and z coordinates of three reference points on the maxillary cast were determined with a machinist microscope relative to a fixed reference after each facebow transfer. A range of differences between mountings of the maxillary cast were found between trials with all three methods used. These mounting errors were due to setting of the instrument and would be expected in routine clinical use of this instrument. PMID- 1507133 TI - Determining the occlusal plane with the Camper's plane indicator. AB - Camper's line has been used by many dentists as a reference in determining the plane of occlusion in edentulous patients. This article describes an instrument that provides the dentist with a clear and accurate assessment of the occlusal plane in relation to Camper's line. PMID- 1507134 TI - Racial norms: esthetic and prosthodontic implications. AB - A review of the orthodontic literature reveals that different races have different cephalometric norms. This has great implications in the placement and arrangement of teeth and in the evaluation of esthetics in people of dissimilar ethnic origins. In the diverse American society, prosthodontists and restorative dentists need to be concerned with the phylogenetic characteristics of their patients. The resultant esthetic differences can have significant importance in the function and design of prostheses. PMID- 1507135 TI - The UCLA abutment: a four-year review. AB - The UCLA abutment has been used over the past 4 years in the restoration of osseointegrated implants. The design of the abutment allows fabrication of the restoration directly to the implant fixture, bypassing the transmucosal abutment cylinder. This technique is valuable in overcoming problems of limited interocclusal distance, interproximal distance, implant angulation, and soft tissue response. Another major advantage with the UCLA abutment is that of improved esthetics. After treatment of 46 patients with 118 UCLA abutments, the 4 year success rates are 95.8%. PMID- 1507136 TI - Silicone nasal radiation carriers. AB - A technique for fabrication of a flexible shielded afterloaded silicone nasal radiation carrier is described. The technique uses a rubber base impression of the nasal cavity from which a silicone radiation carrier is made. Plastic tubes for afterloading of the radioactive sources and a lead shield were incorporated into the carrier. The carrier permitted accurate location of the radioactive sources in the nasal cavity and reduced the radiation exposure. PMID- 1507137 TI - Occlusal adjustment as treatment for tenderness in the muscles of mastication in category 1 patients. AB - When a lateral pterygoid muscle is more tender to palpation than the other muscles of mastication, and a stress test is positive, an occlusal cause should be suspected. Patients with lateral pterygoid tenderness are divided into three categories according to two criteria: the position of the condyles in their glenoid fossae and the degree of dysfunction in the articulation. Only patients in category 1, those with a centered condylar position and without dysfunction, are discussed in this article. Occlusal adjustment is executed on the basis of information gathered from radiographs of the temporomandibular joint, diagnostic casts, and leaf gauge measurements of unequal bilateral occlusal contact. The amount of tooth structure requiring removal can be determined by using leaf gauges of differing thicknesses. Occlusal adjustments are performed without mandibular manipulation until the tenderness of the lateral pterygoid muscle is relieved. PMID- 1507138 TI - Passive eruption in the treatment of craniomandibular dysfunction: a posttreatment study of 151 patients. AB - There is sparse posttreatment evaluation of craniomandibular dysfunction (CMD). This study describes the use of an orthopedic interocclusal appliance with passive eruption for the treatment of CMD. The clinical results of 151 patients treated using the passive eruption procedures were assessed at a follow-up time averaging 1.75 years after treatment with a highly structured telephone interview questionnaire. The treated patient population was chronic, averaging 2.58 years in pain and 2.25 previously ineffective treatments for their CMD. Although this was a subjective inquiry, the treated patients confirmed significant reductions in symptoms, a decrease in pain and interference ratings, and reduced health care utilization. A subgroup of 38 patients who previously had no relief with flat plane therapy exhibited similar positive results. Treatment failures were also assessed but were low. The results are discussed in terms of the patients' support of the efficacy of the passive eruption procedure, including the need for future research. PMID- 1507140 TI - The bond strength of elastomer tray adhesives to thermoplastic and acrylic resin tray materials. AB - This study evaluated the bond strength of selected impression materials (Permlastic, Express, and Hydrosil) to a thermoplastic custom tray material as a function of drying time of the adhesive after application to a tray material. In addition, bond strengths of a polysulfide impression material to an acrylic resin tray material and to a thermoplastic tray material made directly against wax were evaluated. Bond strengths were obtained directly from values of applied load at failure and important conclusions were drawn. PMID- 1507139 TI - Microbial contamination in two antimicrobial and four control brands of alginate impression material. AB - Previous investigations have revealed commercial alginate impression material to be contaminated with viable microorganisms. Some manufacturers are now producing alginate materials that contain antimicrobial agents. The purpose of this study was to test and compare two antimicrobial and four control brands without antimicrobial agents of commercial dental alginate impression material for the presence of viable microorganisms. Forty-eight or 96 measured samples of each brand were taken from previously unopened containers using a sterile technique. The samples were placed on chocolate agar plates and in thioglycolate broth tubes and were incubated along with appropriate parallel controls. After incubation, colonies were enumerated, gram-stained, and identified using standard microbiologic methods. The two antimicrobial brands contained viable organisms in 12.5% of the samples incubated on agar media and also contained such organisms from 0% to 16.7% of the samples incubated in thioglycolate media. The four control brands contained viable organisms in from 29.2% to 100% of the samples incubated on agar media and also contained these organisms in from 25% to 79.2% of the samples incubated in thioglycolate media. There was a statistically significant difference (p less than 0.05) in contamination frequencies among some brands. Contamination frequencies of the top and middle portions of the containers did not differ significantly. The concentration of organisms in contaminated samples was 2.8 colony-formed units (CFUs) per gram for the antimicrobial alginates, and from 9 to 161.1 CFUs per gram for the control brands.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1507141 TI - Electromyographic activity of the jaw-closing muscles in patients with osseointegrated implant fixed partial dentures. AB - The control of postural and synergistic jaw reflexes involves interrelated sensory input from receptors in the jaw muscles, temporomandibular joint, periodontal ligament, and mucosa. This investigation was done to determine whether a decrease in intraoral sensory afferent discharge significantly altered the onset of the jaw-unloading reflex. The subject population consisted of three groups with 10 subjects in each group. Group 1 had maxillary and mandibular natural teeth and group 2 consisted of edentulous subjects with complete dentures. Group 3 consisted of edentulous subjects with maxillary complete dentures and mandibular complete implant-supported prostheses. The unloading reflex was initiated with a muscle-unloading device and recorded with a storage oscilloscope. A one-way analysis of variance found no significant differences in the unloading-reflex latency for the masseter or temporal muscles among the three experimental groups (p less than 0.05). PMID- 1507142 TI - Applying business principles to a prosthodontic practice. AB - Determining the optimum fee for prosthodontic services is difficult. Most methods of determining fees are based on comparisons with other practitioners or with established fee schedules. However, comparisons alone are inadequate because they ignore the practitioner's underlying costs. Since it costs each individual practitioner different amounts to produce dentistry, dental fees should be highly individualized. This article presents a model for evaluating fees for prosthodontic services based on both underlying costs and intangible variables such as the dentist's skill, experience, and quality of care. PMID- 1507143 TI - Evaluation of heat-cured resin bases following the addition of denture teeth using a second heat cure. AB - This study compared heat-cured acrylic resin denture baseplate distortions following a second heat cure used to add the denture teeth. The second heat cure was done with three different water-bath curing temperatures. The distortions were evaluated in three planes by use of a measuring microscope. Recorded distortions were not clinically significant. PMID- 1507144 TI - Equipping a dental laboratory: making a shell blaster. AB - A shell blaster has many uses in a dental laboratory. However, because of the size and expense of this piece of equipment, it is not often found in many office laboratories. This article describes a method for making a relatively small, fully functional shell blaster for less than one hundred dollars. The shell blaster can be changed into a sandblaster by removing the walnut shells and refilling it with 26-grit aluminous oxide. PMID- 1507145 TI - Removable prosthodontic laboratory survey. AB - This article presents a brief review of the literature concerning the curriculum deemphasis for removable prosthodontics, especially on the subject of complete dentures. The authors surveyed commercial dental laboratories specializing in removable dental prosthetics in three major Texas cities to determine whether dentists were submitting adequate records and information with their complete denture work authorizations. Results indicate that dentists are requesting services from their laboratories without providing adequate records. PMID- 1507146 TI - A simplified matrix for making direct cores. AB - This article describes the use of a pharmaceutical gelatin capsule as a matrix for making various posted and nonposted crown substructures. The procedure used for a cast post and core using this matrix is outlined. PMID- 1507147 TI - Making an alternative occlusal splint. AB - An occlusal splint is commonly used in the diagnosis and management of temporomandibular disorders. In a partially edentulous patient a poorly adapted removable partial denture can prevent the use of a conventional occlusal splint. This article describes the fabrication of an occlusal splint that also incorporates a provisional removable partial denture. PMID- 1507148 TI - Remake of a porcelain veneer facing after construction of a removable partial denture. PMID- 1507149 TI - Eliminating coronal discoloration when cementing all-ceramic restorations over metal posts and cores. AB - Opaque procelain was fused over metal posts and cores. This procedure permitted the definitive all-ceramic restorations to possess a more uniform shade between teeth restored with metal posts and cores and adjacent vital teeth. PMID- 1507150 TI - Kleptomania: a review of the research. AB - Research on kleptomania is limited. Earlier views and recent reports of treatment are reviewed in this article. More study is needed to delineate this impulse control disorder. PMID- 1507151 TI - Intensity of midlife crisis on responses to the Death Concern Scale. AB - The relationships that exist between the intensity of midlife crisis and individual items on Dickstein's (1972) Death Concern Scale were explored. The question of whether the intensity of a crisis could be used to predict responses to items on the scale was also investigated. A group of 235 person, 30-60 years of age, completed the scale. Pearson product-moment correlation coefficients indicated relationships for 7 of the 30 items on the scale. Using forced-entry regression, with intensity of crisis as the independent variable and the items on the scale as dependent variables, I found 8 scale items with reportable beta scores of .10 or above. The relationships and predictors reflected cognitive and emotional aspects of death. PMID- 1507152 TI - Degree of asymmetry in lateral preferences: eye, foot, ear. AB - Lateral asymmetry in eye, foot, and ear preference was measured using a 15-item questionnaire administered to 442 subjects. Degree and magnitude of asymmetry were greatest for eye, followed by foot and ear. Intercorrelations of lateral preferences were all positive and significant. Two primary factors, eyedness and earedness, were established. PMID- 1507153 TI - A study of the comparative structure of guilt and shame in a Chinese society. AB - On the basis of previous theoretical and empirical analyses of the comparative structures of guilt and shame, the authors hypothesized that antecedent condition (personal inadequacy vs. moral norm violation), audience presence, and personal responsibility attribution would distinguish shame from guilt. Although the subject population was Hong Kong Chinese, evidence from previous studies suggests that the comparative structures of guilt and shame are quite similar across cultures. The subjects were asked to recall either a guilt or a shame incident, and their responses were then coded into the predictor variables. The results of the study indicated that guilt was most likely to emerge when individuals had violated a moral norm and held themselves responsible for their conduct. In contrast, shame emerged more frequently when subjects felt personally inadequate than when they had violated moral norms. Moreover, when a guilt incident was reported, and audience was rarely mentioned, whereas subjects who reported a shame incident would generally feel personally responsible and often mentioned being looked at or evaluated. However, neither personal responsibility nor the presence of an audience seemed to be essential for a person to experience shame. PMID- 1507154 TI - Correlates of a residential pesticide contamination in a self-selected sample. AB - We evaluated the behavioral, health perception, and physical health correlates of a residential pesticide misapplication on 54 individuals and identified factors differentially related to various levels of distress. Study participants were mainly concerned with health issues and exhibited somatic symptoms. Behavioral actions designed to obtain information regarding exposure levels and to reduce exposure were adopted. We found that factors such as a higher contamination level, involvement in a lawsuit, and belonging to a consumer action group, were strongly related to higher levels of psychological distress and, to a lesser extent, to behaviors, somatic symptoms, and health perceptions. PMID- 1507155 TI - Opponent colour coding is a universal strategy to evaluate the photoreceptor inputs in Hymenoptera. AB - Behavioural tests were carried out with 9 hymenopteran insect species, which ranked certain sets of coloured stimuli according to their subjective similarity to a previously memorized stimulus. Kendall's tau co-efficient is employed for the analysis of correlation between these similarity rankings and the colour distance rankings predicted by various models of neural colour computation. The models are based on the measured spectral sensitivities of photoreceptor colour types and use a variety of simple colour coding systems to derive hypothetical colour distances. The correlation between the predictions of the models and the behavioural results serves as a measure for the likelihood of existence of a colour coding system. In all species, the similarity rankings can be best explained by assuming that colour is coded on a perceptual level by two colour opponent mechanisms. Brightness differences are ignored, indicating that an intensity-coding sub-system is not used in colour discrimination by the insects investigated. The weighting factors of the colour opponent mechanisms differ between species in detail, but not in the principles involved. It is thus possible to employ a standard measure of perceptual colour distance (colour hexagon distance) to predict the capacities of colour discrimination adequately in all the tested insects. PMID- 1507156 TI - The refractive development of the eye of the American kestrel (Falco sparverius): a new avian model. AB - Most measures of avian visual performance are carried out on commonly available domestic species such as the chicken, and most of the data on avian induced refractive error deals with chickens. Raptors are predatory birds in which good visual resolving ability is particularly important. Behavioral studies indicate that the eyes of raptors have two to three times the resolving ability of the human eye. The domestic chicken is precocial at hatching whereas most raptors are semi-altricial. This study was an effort to determine if the effect of early visual deprivation on the refractive development of the chicken eye can be reproduced in the American kestrel, a species which is not domesticated and in which the need for acute vision is particularly important. Visual deprivation was achieved by unilaterally applying translucent plastic goggles over the eyes of kestrels two days after hatching. Refractive error was measured using a retinoscope and trial lenses. Ocular growth was monitored by A-scan ultrasonography, and frozen ocular sections of sacrificed birds. The effect of the experimental manipulation on the contralateral control eye and body weight was evaluated each day over a 42-day period. The goggles did not significantly affect the normal changes in body weight or the normal pattern of ocular growth and refractive development in the untreated eyes. An analysis of the refractive state changes as a result of form deprivation was made each week for 6 weeks after hatching on both the treated and untreated eyes in a separate group of experimental birds. Visual form deprivation caused a significant myopic shift in refractive error and a significant increase in the vitreous chamber depth in the treated eyes at 3 and 6 weeks of age. However, the amount of myopia produced is much less than that induced in chicks, and in certain cases hyperopia is produced. The kestrels recover from myopia and hyperopia within 10 days of goggle removal, after 3 to 4 weeks of deprivation. This study is the first indication that chickens may not be a representative bird model for studying form deprivation myopia. First, myopia is not always produced in kestrels in response to form deprivation. Second, kestrels are severely myopic at hatching and therefore, the direction of emmetropization is opposite to that found in hatchling chicks. PMID- 1507157 TI - Directionality of phase locking in auditory nerve fibers of the leopard frog Rana pipiens pipiens. AB - A dorsal approach to the eighth nerve and free-field stimulation were used to investigate the effect of sound direction and intensity on phase locking in auditory nerve fibers of the leopard frog Rana pipiens pipiens. Tuning curves of 75 auditory neurons were analyzed (Fig. 2). Amphibian papillar neurons, but not basilar papillar neurons, exhibit significant phase locking to short tone bursts at the characteristic frequency (CF), the degree of phase locking (vector strength) decreasing with the neuron's CF (Figs. 3, 4 and 10E). Vector strength increases with sound pressure level to saturate about 20 dB above threshold, while the preferred firing phase is only slightly affected (Figs. 5 and 6). In contrast, sound direction hardly affects vector strength (Figs. 7, 8, 9A and 10A and C), but has a strong influence on the preferred firing phase (Figs. 7, 8, 9B and C, 10B and D): With respect to anterior tone presentation there are phase lags for ipsilateral and phase leads for posterior and contralateral presentation. Phase differences between both ears show a sinusoidal or cardioid/ovoidal directional characteristic; maximum differences are found with antero-lateral tone presentation (Fig. 11). The directionality of phase locking decreases with the neuron's CF (Fig. 10F) and only slightly changes with sound pressure level (Fig. 12). Thus, phase locking of amphibian papilla neurons can potentially provide intensity-independent information for sound localization. PMID- 1507158 TI - Enhancement of sensitivity in photoreceptors of the honey been drone by light and by Ca2+. AB - Deeply dark adapted (1 h) photoreceptor cells of the honey bee drone show a light induced enhancement of sensitivity (facilitation) as an aftereffect of illumination or in the presence of dim backgrounds. The Ca(2+)-dependency of this effect was studied: Reduction of extracellular Ca2+ to 0.1 mM decreases the sensitivity of a dark adapted cell, and the light-induced increase in sensitivity due to repetitive, dim, 20 ms test flashes is slower than in normal saline. After a sensitizing conditioning light, the sensitivity drops faster in low-calcium saline. The light-induced enhancement of sensitivity is mimicked by pressure injections of low amounts of Ca2+ (Ca2+/EGTA-buffers; 0.15 microM free Ca2+) into a dark adapted cell. Injection of EGTA alone decreases the sensitivity. Injection of a solution containing ca1 mM free Ca2+ sequentially decreases and later increases the sensitivity transiently. These results suggest a model in which a progressive increase in intracellular Ca2+ concentration by light first increases (facilitates), and, at higher concentrations, decreases (light adapts) the sensitivity of the cells. One possible site of action for this positive and negative feedback control of cell sensitivity by Ca2+ is the endoplasmic reticulum. PMID- 1507159 TI - Effects of physiological cycles of infused melatonin on circadian rhythmicity in pigeons. AB - The role of the hormone melatonin in the circadian system of pigeons (Columba livia) was investigated. Using an automatic infusion system, melatonin at physiological levels was delivered for 10 h each day to cannulated, pinealectomized (P-X) pigeons in constant darkness. These cyclic infusions of melatonin entrained feeding rhythms in P-X pigeons while vehicle infusions were ineffective entraining agents. When the retinae of P-X pigeons were removed (E X), feeding rhythms were abolished in constant darkness. When cyclic melatonin infusions were delivered to these birds (E-X and P-X), feeding rhythmicity was restored whereas vehicle infusions alone did not restore rhythmicity. When melatonin infusions were terminated in E-X/P-X pigeons, feeding rhythms persisted for several days but eventually decayed. Blood melatonin levels were measured in both P-X and E-X/P-X birds infused cyclically with exogenous melatonin and were found to be within the physiological range both in level and pattern. These results strongly suggest that endogenous melatonin, released by the pineal gland and the retinae, regulates the timing of feeding rhythms by entraining other oscillators in the circadian system of the pigeon. PMID- 1507160 TI - The influence of tactile stimulation of nipples on the milk ejection reflex in the rat. AB - Changes of positive pressure exerted by pups on nipples during sucking were investigated using anesthetized, lactating dams. It was found that, every 50-60 s, individual pups performed bouts of pressure oscillations (3/s) of high amplitude which lasted about 10-12 s and coincided with periods of increased motor activity. During the intervals, when pups were quiet, series of low amplitude oscillations (3/s) were also observed. Using a strain measuring method to record the activity of sucking pups, synchronization of activity of two or more pups was found to occur periodically every 25-30 s and, most frequently, 10 30 s before the reflex increase of milk pressure. In further experiments, artificial tactile stimulation was applied to the dam's nipples using the joint action of suction and positive pressure. Following a short-term (10-20 s) increase in frequency and amplitude of artificial nipple stimulation, 60%-80% of all reflexive peaks of milk pressure were elicited with a latency of 19 +/- 5 s. This suggests that there are specific conditions under which the stimulation of nipples by pups may trigger the formation of the milk ejection reflex in the rat. PMID- 1507161 TI - Electroantennogram of the American cockroach: effect of oxygen and an electrical model. AB - 1. With a view to clarifying the role of oxygen in the olfactory reception of insects, the intact antenna of the male American cockroach (Periplaneta americana) was studied under normal conditions and during reversible anoxia, external or tracheal, using an electroantennogram (EAG) elicited by a sex pheromone stimulation. As a first step, the anatomical and electrical characteristics of the antenna were investigated. 2. Based on the microanatomical study, a cockroach antenna was characterized by structural parameters reflecting the haemolymph and gas exchange in the antenna. Valves in the wall of a haemolymphatic vessel were discovered. 3. The resting DC background voltage (DCBV) and the EAG were continuously recorded and proved to be more strongly affected by tracheal anoxia than by anoxia from the outside. 4. A minimal electrical model of the antenna based on the Thurm-Kaissling-De Kramer equivalent circuit of a sensillum was shown to be valid to explain the origin of the DCBV and EAG as well as their changes after oxygen cutoff and resumption. 5. Two formal opposing processes, excitation and desensitization, probably related to the receptor mechanisms, have been used to interpret the kinetics of the EAG and the effect of anoxia on EAG parameters. The desensitization is thought to be more sensitive to oxygen lack than the excitation. PMID- 1507162 TI - Reflections on the past, present and future of automated aberration scoring systems for radiation dosimetry. PMID- 1507163 TI - Programmed cell death in whole body and organ systems by low dose radiation. AB - New whole-body and organ systems were established to detect interphase cell death in the thymus, spleen and epithelial cells of intestinal crypts by low-dose radiation. Frozen sections of the thymus, spleen and intestine as thick as 8 microns were made after X-irradiation of whole body or removed organs, and then sections were stained with 0.02% erythrosin B solution. In unirradiated controls, a few numbers of erythrosin B positive cells (dead or dying cells) were observed in the thymus, spleen and intestinal crypt as a single cell death. When X rays were given to various strains of mice as a whole body dose, clusters of erythrosin B positive cells were produced. They appear at 2 hr after irradiation and reached maximum at 4 hr, remaining at a similar level until 8 hr after irradiation. The number of erythrosin B positive cells decreased after then by the elimination of dead cells, and they were observed like a single cell death at 24 hr after irradiation. When erythrosin B positive cells were scored 4 hr after irradiation, their total number and the number of cluster increased with increasing doses of X rays in the dose range from 0.05 to 0.5 Gy. It is noted that there were large differences in the radiation susceptibility among the inbred strains of mice for the induction of interphase cell death of thymic lymphocytes: e.g., high susceptibility in C57BL/6J and AKR/J, intermediate in N4, A/J, PT and ST, low in C3H/HeJ, HT, 101/H and DBA/2J, indicating that interphase cell death is genetically programmed. Similar results were observed with some chemical mutagens. Although a large increase of erythrosin B positive cells was observed in the thymus and spleen with methylprednisolone, there was no increase in the intestinal crypt, and vice versa with bleomycin, suggesting the organ specificity for the induction of interphase cell death by chemicals. For the in vitro method, the removed thymus was irradiated on the agar plate, and then incubated on the agar plate which was placed on the grid in the medium, so that the medium comes up to the organ through the agar plate. Frozen sections were made and stained with erythrosin B solution in the same way as the in vivo method. The number of erythrosin B positive cells in the organ culture system reached maximum at 5 hr after X-irradiation, e.g. slightly later than in the whole-body system. The efficiency was about 60% in C57BL/6J mice when compared with whole-body system. PMID- 1507164 TI - The PSI automatic metaphase finder. AB - The Genetiscanner automatic metaphase finder (AMF) instrument manufactured by Perceptive Scientific Instruments, Inc. is capable of searching a microscope slide and generating a list of the stage coordinates of the metaphases within the 20 mm x 40 mm search area in ten minutes. It can process a cassette load of sixty slides in approximately ten hours, ranking the metaphases according to six categories of quality. It uses a robot arm to load and unload slides from a 60 slide cassette onto an automated microscope stage. It searches at approximately 1.5 sq. mm per second and uses automatic focus to keep the image sharp during the search. On good quality blood slides it detects greater than 80% of the metaphases with greater than 80% ranking accuracy and less than 20% false positives. It can also search amniotic fluid, bone marrow and mammalian cell culture metaphase preparations. The pattern recognition algorithms use classifiers specifically trained for each specimen type, and for the rejection of non-metaphase material. Such units have been in continuous operation for up to two years with good performance and reliability. PMID- 1507165 TI - A high resolution chromosome image processor for study purposes, NIRS-1000:CHROMO STUDY, and algorithm developing to classify radiation induced aberrations. AB - Since 1989 we have promoted a project to develop an automated scoring system of radiation induced chromosome aberrations. As a first step, a high resolution image processing system for study purposes, NIRS-1000:CHROMO STUDY, has been developed. It is composed of: (1) CHROMO MARKER whose main purpose is to mark on images to make image data base, (2) CHROMO ALGO whose purpose is algorithm development, and (3) METAPHASE RANKER whose purposes are metaphase finding and ranking with a high power objective lens. However, METAPHASE RANKER is presently under development. The system utilizes a high definition video system so as to realize the best spatial resolution that is achievable with an optical microscope using an objective lens (x 100, numerical aperture 1.4). The video camera has 1024 effective scan lines to realize 0.1 microns sampling on a specimen. The system resolution achieved on the hard copy is less than 0.3 microns on a specimen. A preliminary algorithm has been developed to classify the aberrations on the system using projection information of gray level. The preliminary test results on excellent 10 metaphases show that the correct classification ratio is 92.7%, that the detection rate of the aberrations is 83.3% and that the false positive rate is 6.1%. PMID- 1507166 TI - Automatic assessment of the quality of G-banded metaphases. A preliminary study. AB - Assessment of the quality of cytogenetic preparations is important for 1) a general quality control of the cytogenetic laboratory and 2) for determining the quality of individual cytogenetic analyses. It is generally accepted that good preparations allow a more detailed search for structural abnormalities than poor preparations. As part of a comprehensive study on automated assessment of slide quality we have developed a simple algorithm for automated measurement of metaphase resolution. During semi-automated karyotyping with the Magiscan chromosome analysis system (Joyce-Loebl) three measurements related to resolution are automatically extracted 1) the total number of dark bands of the chromosomes of the metaphase (TB), 2) the normalized average length of the chromosomes (NL), and 3) the average "thickness" of the chromosomes (T). The algorithm TB x NL/T has been tested on 35 metaphases of various quality and compared with visual assessment of the same 35 metaphases. The results indicate that the automatic assessment of metaphase resolution is superior to the visual. PMID- 1507167 TI - Adaptive classifiers for dicentric chromosomes. AB - Classification of dicentric chromosomes in a practical automatic screening system comprises three stages. The first generates plausible centromere candidates from each chromosome in an automatically segmented metaphase, and uses contextual knowledge to generate distributions of "probably true" and "probably false" centromeres, thus adapting to the conditions within a particular metaphase. The second stage classifier uses these distributions to re-classify the candidates as centromeres or non-centromeres. From this classification, likely dicentrics are found by counting centromeres; a third classifier attempts to reject false positives among the likely dicentric chromosomes, by comparing the feature values of the proposed centromeres of a chromosome and rejecting chromosomes for which these values do not satisfy certain similarity criteria. The second stage classifier may be a simple box classifier, or may use a variety of parametric Bayesian methods. The performance of these alternatives has been tested both on reference data sets comprising about 600 metaphases, and on larger data sets when embedded in a practical fully automatic dicentric pre-screening system. When operating parameters were such that a similar number of true positives were found by both classifiers, the Bayesian classifier produced about half as many false positive errors as the box classifier, with the final false positive rate being in the region of one candidate dicentric chromosome in every four cells. PMID- 1507168 TI - Chromosome analysis by image processing in a computerized environment. Clinical applications. AB - Dealing with a routine regional cytogenetic activity, we have developed and adapted to clinical work a semi automatic karyotyping machine. Attempts for an accurate automated chromosome classification using a neural network have led to partial results. A specific adaptation to cancer cytogenetics is under development (determination of the modal number, translocations analysis with densitometric curves, automatic identification of markers). A specific program allows quantification of chromosome labelling with radioactive probes. Exchanges of digitized karyotypes are feasible with labs using automated karyotyping machines. A local network connects several karyotyping and metaphase finding stations. Guidelines for an international data bank concerning abnormal chromosome images have been elaborated. On the other hand the ISH techniques have been applied to the following topics: identification of human chromosome aberrations in amniotic and chorionic cells, chromosome studies of human gametes and embryos (including sex determination), identification of markers in cancer cells. PMID- 1507169 TI - Automated detection of radiation-induced chromosome aberrations following fluorescence in situ hybridization. AB - The cytogenetic detection of rare chromosome aberrations induced by ionizing radiation requires the evaluation of large numbers of cells. In this report, an image analysis program based on thresholding of grey level histograms is described for a rapid automated detection of chromosome translocations in metaphase spreads from human lymphocytes following irradiation and chromosome in situ suppression (CISS) fluorescence in situ hybridization (FISH). To classify a metaphase spread as "normal", "aberrant", or "excluded", a minimum medium time of less than two seconds was required on a general purpose Personal Computer. Using appropriately stained specimen, for the false classification rate an upper limit of about 10% was estimated. The upper limit for the rate of "excluded" cells was estimated to be about 11% (99% confidence ranges). FISH-procedures allow to score chromosome aberrations also in the interphase nucleus. To apply simple threshold algorithms for segmentation of the FISH-stained nuclear areas, it is required that the grey level contrast is sufficiently high. The preliminary results presented here on the image analysis of human lymphocyte nuclei suggest the feasibility of such an approach. PMID- 1507170 TI - Factors that determine the in vivo dose-response relationship for stable chromosome aberrations in A-bomb survivors. AB - An overview is given of the dose-response relationship for stable chromosome aberrations (i.e., translocations and inversions) in the peripheral blood lymphocytes of A-bomb survivors in Hiroshima. Special emphasis is placed on (i) the overdispersion of survivor cases with either unexpectedly high or low aberration frequencies relative to the estimated DS86 kerma values assigned to individual survivors, termed "cytogenetic outliers", and (ii) the correlation of chromosome aberration frequencies with other biological endpoints, such as acute radiation symptoms (severe epilation). A new molecular biological technique, known as fluorescence in situ hybridization (FISH) with composite, whole chromosome probes to paint differentially the target chromosomes, has facilitated rapid, efficient, and extensive scoring of translocation-type chromosome aberrations in which the target chromosomes are involved. Using this methodology, the observed findings on translocation frequencies in A-bomb survivors have shown that the frequency of stable chromosome aberrations, which have persisted for years without change in frequency in irradiated persons, is indeed useful as an indicator for biological dosimetry. PMID- 1507171 TI - A preliminary evaluation of the Edinburgh dicentric hunter. AB - Computer programs have recently been developed to enable automatic detection of dicentric chromosomes on microscope slides. Theoretical calculations based on the probable limits of resolution of such a system suggested that about two thirds of dicentrics might be detectable. We present here some preliminary results from an ongoing evaluation of an automatic dicentric hunter using slides of lymphocyte preparations which have also been examined by eye. The data indicate an efficiency approaching 40% in dicentric detection. PMID- 1507172 TI - Combined use of several mitogens for mitotic stimulation to human lymphocytes. AB - Several different type of mitogens, such as phytohemagglutinin (PHA) including PHA-P, -M, -W, -C, -L and -E+L, pokeweed mitogen (PWM), Concanavalin A (Con-A), lipopolysaccharide (LPS), wheat germ agglutinin (WGA) and soybean agglutinin (SBA) were compared their mitotic stimulating effects to human lymphocytes in single use and also combined use of these mitogens. In the tests with single use of each mitogen, PHA was confirmed to be the most superior mitogen. Of several different types of PHA, PHA-C, -L and -E+L were not appropriate to stimulate human lymphocytes, though PHA-P, -M and -W induced sufficiently mitoses. The most appropriate concentration of PWM was 50 micrograms/ml, but the highest mitotic index reached at 5 days after the initiation of culture. Con-A did not induce sufficient mitoses, and LPS, WGA and SBA were inadequate to stimulate human lymphocytes in the single use. In the combined use of two mitogens, there was no reliable combination to enhance mitotic stimulation. When three different mitogens were used simultaneously, only one combination with PHA-M, PWM and SBA effectively enhanced the mitotic index when compared to the single use. In the confirmatory experiment for this combination carried out on 5 different donors, the enhanced effect to mitotic index was recognized in two out of three donors with low response to PHA, but the low level of mitotic indices was seen in remaining 2 donors with high response to PHA. This finding suggests that this combination may overcome a disadvantage in some of the low responders to PHA. PMID- 1507173 TI - Robot system for preparing lymphocyte chromosome. AB - Towards the automatization of the scoring of chromosome aberrations in radiation dosimetry with the emphasis on the improvement of biological preparations, the conventional culture and harvesting method was modified. Based on this modified method, a culture and harvest robotic system (CHROSY) for system (CHROSY) for preparing lymphocyte chromosome was developed. The targeted points of the modification are as in the following. 1. Starting culture with purified lymphocytes in a fixed cell number. 2. Avoiding the loss of cells in changing the liquids following centrifugalization. 3. Keeping the quantity of the liquids to be applied to the treatments of cells fixed. 4. Building a system even a beginner can handle. System features are as follows. 1. Operation system: Handling robot having 5 degrees of freedom; a rotator incubator with an automatic sliding door; units for setting and removing pipette tips; a centrifuge equipped with a position adjuster and an automatic sliding door; two aluminum block baths; two nozzles as pipettes and aspirators connected to air pumps; a capping unit with a nozzle for CO2 gas; a compressor; and an air manipulated syringe. 2. Control system: NEC PC-9801RX21 with CRT; and program written in Basic and Assembly languages on MS-DOS. It took this system 2 hours and 25 minutes to harvest 2 cultures. A fairly good chromosome slide was made from the sample harvested by CHROSY automatically. PMID- 1507174 TI - Development of an instrument for chromosome slide preparation. AB - For cytogenetic analysis of chromosome abnormalities, we have developed an instrument which can produce semi-automatically chromosome slides for microscopic observation. This instrument has automatic slide supplier and slide transfer system. Chromosome slides were obtained by the steam dry method; slides were sequentially exposed to different atmosphere controlled strictly in respect of temperature and humidity. Slides with well-spread chromosomes were obtained constantly in quality and rapidly in speed of 5 slides per minute. Precise controls of room temperature and humidity were attained by the use of 26 thermomodules. Accuracy of the controls was excellently high, showing a fluctuation of +/- 0.5 degrees C in temperature and +/- 3% in humidity for any setting in the use range. This instrument was proved to be very useful for rapid obtaining of a large number of chromosome slides with highly qualified metaphase spreads. This instrument will be utilized to assist the automation analysis system of chromosome abnormalities. Mechanism of chromosome spreading, problems in actual use, and future improvements were discussed. PMID- 1507175 TI - A neural network chromosome classifier. AB - We present a chromosome classifier for automated karyotyping of banded chromosomes which uses a multi-layer perception neural network. Two network configurations have been investigated. The resulting classifiers have been trained and tested on data from three different data sets covering a range of data quality. Classification results compare very favourably with those obtained using a highly optimised parametric classifier. PMID- 1507176 TI - A comment on some aspects of chromosome aberration analysis for radiation accident dosimetry. PMID- 1507177 TI - Biomedical rationale for cytogenetic dosimetry. AB - The purpose of this presentation is to initiate the discussions of automated analysis of radiation-induced chromosome aberrations with a consideration of the possible biomedical benefits to be achieved by its successful accomplishment. Biological indicators of radiation effect are considered. The biomedical indications for and usefulness of cytogenetic dosimetry are described, based on past experiences and potential applications of the developing technology. The implications of this methodology for both individual and population risk assessment are discussed. Both past experiences and potential applications are considered, with examples, including clinically significant radiation accidents involving radiation workers and members of the public; public health applications in the screening and monitoring of actually and potentially exposed population groups; occupational surveillance of special worker subsets and of the general radiation worker population; and scientific usage in epidemiologic studies and laboratory investigations. PMID- 1507178 TI - Cytogenetic biomonitoring of human radiation exposures: possibilities, problems and pitfalls. AB - The use of chromosome aberration analysis has progressed and is now generally recognized to provide a useful means for the assessment of dose and possible health consequences in human exposures to relatively high doses of ionizing radiations. The automated analysis of radiation-induced chromosome aberrations will facilitate the better understanding of the health effects of radiations on human populations, particularly of those at low levels. However, the reaction kinetics of chromosome aberrations in the low dose or low dose-rate exposures are not well delineated. In this paper, possible reaction kinetics of chromosome aberrations, particularly those in human lymphocyte, in low dose-rate exposures have been discussed based on the cytogenetic data on the Thorotrast patients, persons involved in the protracted occupational exposures and modulation of chromosome aberrations by radioadaptive response. In the protracted low dose-rate exposures, the levels of chromosome aberrations, whether they are stable- or unstable-type aberrations, are not in a simple function of the total accumulated dose due mainly to the lymphocyte kinetics and modulation by cellular stress response. If this formalism is realistic, the dissociation between levels of chromosome aberrations and cancer risks may be large for the low level protracted exposures. PMID- 1507179 TI - Recent advances in fluorescence in situ hybridization. AB - Fluorescence in situ hybridization (FISH) procedures that directly couple molecular and cytological information allow precise visualization of DNA sequences on metaphase chromosomes and interphase nuclei. These techniques can be used to identify chromosomes, detect chromosomal aberrations, and analyze linear and spatial genome organization. FISH procedures are also used to clinical fields for diagnosis of disease-related chromosome changes and tumor biology. PMID- 1507180 TI - Development of a biological dosimeter for translocation scoring based on two color fluorescence in situ hybridization of chromosome subsets. AB - Recently fluorescence in situ hybridization protocols have been developed which allow the painting of individual chromosomes using DNA-libraries from sorted human chromosomes. This approach has the particular advantage that radiation induced chromosome translocations can be easily detected, if chromosomes of distinctly different colors take part in the translocation event. To enhance the sensitivity of this approach two metaphase chromosome subsets A and B (A: chromosomes 1, 2, 4, 8, 16; B: 3, 5, 9, 10, 13) were simultaneously painted in green and red color. Counterstaining of the chromosomes with DAPI resulted in a third subset which exhibited blue fluorescence only. Green-red, green-blue and red-blue translocation chromosomes could be easily detected after irradiation of lymphocyte cultures with 137Cs-gamma-rays. Analyses of painted chromosomes can be combined with conventional GTG-banding analyses. This new biological dosimeter should become useful to monitor both long term effects of single irradiation events and the cumulative effects of multiple or chronic irradiation exposures. In contrast to translocation scoring based on the analysis of banded chromosomes, this new approach has the particular advantage that a rapid, automated scoring of translocations can now be envisaged. PMID- 1507181 TI - A quantitative analysis of radiation-induced chromosome aberrations with a fluorescent digital image microscope. AB - Using a synthetic, alpha satellite consensus DNA unit as a probe, we could show dicentrics as well as acentric fragmented chromosomes in metaphases of gamma irradiated lymphocyte cells and that the number of appearance of dicentrics or acentric fragments seemed to be proportional to radiation doses. To make such examination with a large number of chromosomes of metaphases, a quantitative fluorescence measurement was performed using a fluorescent microscope digital image analysis system. The relative amounts of fluoresceinated probe hybridized to alpha satellite DNA varied with chromosomes to a certain extent (1-4% of total probe-fluorescence of one metaphase). However, we could score dicentrics and acentric fragments as dots with extraordinarily higher or low percentage in plots of relative amount of probe-fluorescence on metaphase chromosome in gamma irradiated cells. The number of appearance of acentric fragments were proportional to radiation doses of 1, 2 and 4 Gy. In the case of dicentrics, the number of appearance seemed to be proportional to square doses. Further, to reduce the variation of relative amounts of probe-fluorescence, we tried to make probe-fluorescence reflect the content of alpha satellite DNA on each chromosome more exactly, using a DNA probe amplified by polymerase chain reaction. PMID- 1507182 TI - Radiation-induced chromosome damage in G1 phase cells as breaks in premature chromosome condensation (PCC) and its biological meaning. AB - We studied radiation-induced chromosome fragmentation in the G1-phase of Syrian golden hamster embryo (SHE) cells by premature chromosome condensation (PCC). SHE cells were irradiated with 14N ions (95 MeV) and 4He ions (22 MeV) generated by the cyclotron and 137Cs gamma rays. The number of chromosome breaks in PCC (PCC break) induced by 14N ions was higher than in those by the others. High linear energy transfer (LET) radiation (heavy ions) is more effective in the induction of PCC breaks than low LET radiation (gamma-rays). 530 kev/microns 14N induced PCC 2.4 times more than 137Cs gamma rays. There is an inverse relationship between the number of chromatid deletions and the incidence of mutation or transformation. There is, however, a good correlation between the incidence of PCC breaks and frequencies of mutation and/or morphological transformation. Although over 95% of the PCC breaks induced by gamma-rays were rejoined within 8 hours of post-irradiation incubation, only 35 to 45% of PCC breaks induced by heavy ions were rejoined. These results suggest that there is a qualitative difference in the initial chromosome damage caused by heavy ions and gamma rays. PMID- 1507183 TI - Resolution and characterization of polymorphic DNA by SSCP and chemical cleavage methodologies. AB - A variety of techniques have been developed to detect single-base changes for the two different purposes. One is the detection of mutational events without phenotypic selection, and another is the rapid and conventional identification of mutations such as the specific base changes related to activation of oncogene, genetic diseases, etc. In this study, the utility of the two methods, single strand conformation polymorphism (SSCP) and chemical cleavage, was explored using 13 E. coli lacI- mutations cloned onto M13 phase. The 167 base region encompassing mutations was amplified by PCR as dsDNA. Following denaturation, these PCR products were analyzed by non-denaturing polyacrylamide gel electrophoresis (SSCP) and the separation of the ssDNA fragment carrying the altered sequence from the original sequence was found to be dependent on the location and type of the change. Hetero duplexes of changed/original sequences were also prepared by hybridization of the above PCR products. Mismatched C and T bases were modified by hydroxylamine and osmium tetroxide, respectively, and subsequently treated with piperidine to analyze the cleaved DNA fragments on a polyacrylamide gel (Chemical Cleavage). The cleavage efficiency was also found to be influenced by the type of mismatch and its surrounding sequence. Such observed characteristics should contribute to a better appreciation for these types of mutational systems, which in turn should lead to insight into the mechanisms of mutagenesis. PMID- 1507184 TI - Species- and subtype-specific recognition by antibody WF6 of a sequence segment forming an alpha-bungarotoxin binding site on the nicotinic acetylcholine receptor alpha subunit. AB - The monoclonal antibody WF6 competes with acetylcholine and alpha-bungarotoxin (alpha-BGT) for binding to the Torpedo nicotinic acetylcholine receptor (nAChR) alpha 1 subunit. Using synthetic peptides corresponding to the complete Torpedo nAChR alpha 1 subunit, we previously mapped a continuous epitope recognized by WF6, and the prototope for alpha-BGT, to the sequence segment alpha 1(181-200). Single amino acid substitution analogs have been used as an initial approach to determine the critical amino acids for WF6 and alpha-BGT binding. In the present study, we continue our analysis of the structural features of the WF6 epitope by comparing its cross-reactivity with synthetic peptides corresponding to the alpha 1 subunits from the muscle nAChRs of different species, the rat brain alpha 2, alpha 3, alpha 4 and alpha 5 nAChR subtypes, and the chick brain alpha-BGT binding protein subunits, alpha BGTBP alpha 1 and alpha BGTBP alpha 2. Our results indicate that WF6 is able to cross-react with the muscle alpha 1 subunits of different species by virtue of conservation of several critical amino acid residues between positions 190-198 of the alpha 1 subunit. These studies further define the essential structural features of the sequence segment alpha 1(181-200) required to form the epitope for WF6. PMID- 1507185 TI - Scintillation proximity assay to study the interaction of epidermal growth factor with its receptor. AB - Scintillation Proximity Assay (SPA), which does not require the physical separation of receptor bound and free ligand, was applied to study the interaction of Epidermal Growth Factor (EGF) with its receptor (EGFR) in membrane preparations from human placenta. Fluomicrospheres to which the monoclonal anti EGFR antibody R1 was coupled, were used. Kinetic binding data of the association of 125I-labeled EGF binding to the receptor at 20 degrees C could be fitted according to a double exponential model, which is consistent with the presence of fast and slow associating EGF binding sites. Dissociation kinetics revealed that perturbation of equilibrium conditions rapidly occurs upon washing. Multiple point Scatchard analysis of equilibrium 125I-labeled EGF binding data revealed curvilinearity, indicating the presence of both high and low affinity EGF binding sites. We conclude that SPA is an interesting new tool in the exploration of the interaction of ligands with their receptors, which allows detailed ligand receptor studies under precise in situ conditions. PMID- 1507186 TI - Prenatal diagnosis in the '90s. A symposium. PMID- 1507187 TI - Chorionic villus sampling. PMID- 1507188 TI - Early amniocentesis. AB - Early amniocentesis (EA) refers to any genetic amniocentesis performed prior to 15 weeks, 0 days' gestation. Because of technical problems, most practitioners stopped doing amniocenteses prior to 15 weeks' gestation in the late 1970s. The development of ultrasound-monitored needle insertion has allowed improved success and safety of sampling at earlier gestations, and improvements in laboratory techniques have allowed a high degree of success in culturing and processing low volume samples. We present information on 1,805 early amniocenteses, of which 35% were performed prior to 14 weeks, 0 days' gestation. Our data indicate that with operator experience the success rate of the procedure can be similar to that seen with routine amniocentesis and that laboratory experience is not different from that with routine amniocentesis (RA) as measured by culture success, time to completion and accuracy. Pregnancy outcome, as measured by the gestational age at delivery, mode of delivery, birth weight and Apgar score, is indistinguishable between RA and EA patients. Although a randomized study is needed to accurately evaluate the fetal loss rate, the rate of birth defects and incidence of neonatal complications associated with EA procedures and examination of the crude rates for the above three parameters show that they compare favorably to the rates reported for patients who have undergone chorionic villus sampling or RA. PMID- 1507189 TI - Fetal cells in the maternal circulation. AB - The analysis of fetal cells from the maternal circulation would be the least invasive method of prenatal diagnosis. Potential fetal cell types to enter the maternal circulation are lymphocytes, trophoblast cells and nucleated erythrocytes. With conventional methods, such as cytology and interphase or metaphase cytogenetics, the ratio of fetal to maternal cells was overestimated in the past. Currently most groups use polymerase chain reaction-based Y-sequence analysis for the detection of fetal cells in pregnancies with male fetuses, either with or without prior enrichment of fetal cells. For fetal cell separation, fluorescence-activated cell sorting and immunomagnetic beads have been applied, and recently our group has used discontinuous density gradient centrifugation for this purpose. We have shown that the transferrin receptor antigen alone is not sufficient for enrichment of fetal nucleated erythrocytes. Despite some initial promising results with fluorescence in situ hybridization, the reproducibility and reliability of the techniques are still limited, mainly due to the lack of very specific cell markers and the very low and variable concentrations of fetal cells among numerous maternal cells. PMID- 1507190 TI - Ultrasound detection of genetic anomalies. AB - The prenatal detection of genetic diseases has improved remarkably. This review highlights several diagnoses that are possible to identify by ultrasound examination of the fetus, including cystic fibrosis, skeletal dysplasias, kidney diseases, cardiac disease and central nervous system disorders. Ultrasound clues to the possible existence of several syndromes and aneuploidy are also outlined. PMID- 1507191 TI - Preimplantation genetic analysis. AB - Advanced reproductive technologies have afforded us access to human preembryos, allowing the possibility of preimplantation genetic diagnosis of certain genetic diseases. This paper thoroughly reviews both the micro-manipulation and molecular biologic aspects of this new and exciting branch of medicine. In addition, some of the moral and ethical considerations relating to preembryo genetic diagnosis are discussed. PMID- 1507192 TI - Molecular diagnosis of genetic disease. AB - DNA-based testing is becoming possible for an increasing number of hereditary diseases as the responsible genes are mapped to individual chromosomes and then isolated and characterized. The strategy for each test depends on the heterogeneity of mutations commonly causing the disease, the distribution of the mutations in the population and the frequency of new mutations. In many cases, interpretation of the test result requires a comparison with relatives known to carry the abnormal gene. Sickle cell anemia is an example of a recessive mutation with a strong ethnic association and little genetic heterogeneity or new mutation. Cystic fibrosis also has a strong ethnic association and a low frequency of new mutation but greater heterogeneity. Fragile X affects all ethnic groups and often appears sporadic, but all cases have the same type of mutation, and a premutation can be found in all affected families. In the near future, the extreme sensitivity of DNA analysis will allow testing for these and similar diseases to be performed in vitro on fertilized embryos before implantation. PMID- 1507193 TI - Third-trimester uterine rupture after prostaglandin E2 use for labor induction. AB - Prostaglandin E2 is a powerful oxytoxic agent that reliably initiates labor, even in the presence of an unripened cervix. The very low incidence of obstetric and neonatal side effects contributes to its universal use. Only nine cases of uterine rupture during the third trimester of pregnancy after application of various prostaglandin E2 preparations have been reported in English. Although uterine rupture after prostaglandin administration is a very rare complication, no prostaglandin compound seems to be exempt from it. PMID- 1507194 TI - Vaginal birth after cesarean section in rural Zaire. Changing concepts. AB - The safety of trials of labor after cesarean section has yet to be established in developing countries. Centre Medical Evangelique is a referral hospital in rural northeastern Zaire. From August 1, 1989, to January 15, 1990, 33 women with previous cesarean deliveries were offered a trial of labor. Of them, 22 (67%) had successful vaginal deliveries. The indications for the previous cesarean section did not influence the outcome of the trial of labor. There was a high rate of immediate maternal morbidity but no significant long-term morbidity. The rate of uterine dehiscence was 9.1%. The perinatal death rate, 60.1/1,000, was similar to the overall rate for the institution. Trials of labor after cesarean section are a valid therapeutic option in developing countries. PMID- 1507195 TI - Eclampsia complicating a pregnancy with neurofibromatosis. A case report. AB - Neurofibromatosis occurs in approximately 1 in 3,000 births and is known to be associated with the development and/or worsening of hypertension in pregnancy. A woman was treated for eclampsia with neurofibromatosis and had a complicated course. PMID- 1507196 TI - Neisseria sicca endocarditis complicating pregnancy. A case report. AB - Neisseria sicca, a commensal organism of the oropharynx, has rarely been implicated as a pathogen responsible for causing bacterial endocarditis. A pregnant woman developed N sicca endocarditis at 32 weeks' gestation. Although there was an initial delay in diagnosis and therapy, the maternal and fetal outcomes were excellent. PMID- 1507197 TI - Cervical pregnancy. A case report. AB - A cervical pregnancy was treated successfully with systemic methotrexate and folic acid. Serial beta-human chorionic gonadotropin levels, color Doppler velocimetry and hysteroscopy were used to monitor therapy. In view of the substantial morbidity associated with this form of ectopic pregnancy, medical management is an option for treatment. PMID- 1507198 TI - Mapping the binding site of tissue kallikrein: preparation and testing of all possible substrate analog inhibitors homologous with the sequence of kininogen between Ser386 and Gln392. AB - Programs aimed at converting peptide inhibitors of proteolytic enzymes into more traditional drug structures require an understanding of the role played by the individual amino acid residues in the inhibitor. To this end, all possible substrate analogues occurring within the sequence Ser386-Pro-Phe-Arg-Ser-Val Gln392 from bovine kininogen were synthesized and tested as inhibitors of tissue kallikrein (EC 3.4.21.35, beta-PPK). Of the 21 sequences which can be formed from the heptapeptide, 11 have inhibitory constants which could be measured in the chromogenic assay employed in these studies. No dipeptide and only one tripeptide, Ac-Phe-Arg-Ser-NH2 (Ki = 718 microM), measurably inhibits the enzyme. All longer peptides inhibit beta-PPK. The heptapeptide Ac-Ser-Pro-Phe-Arg-Ser-Val Gln-NH2 is the most effective inhibitor in this series (Ki = 101 microM). Each amino acid residue in the sequence appears to alter binding in a relatively independent manner. The N-terminal seryl residue (P4) and the prolyl residue (P3) slightly improve the Ki of the various inhibitors. The phenylalanyl residue at P2 appears to have a more pronounced effect on Ki. The arginyl residue at P1 and the seryl residue at P1' appear to be the most important residues in the inhibitory sequence. They contribute approximately one-third and one-fourth of the binding energy to the interaction between the substrate analogues and beta-PPK, respectively. The valyl residue at P2', and the C-terminal glutaminyl residue improve Ki of each of the peptides tested. Almost 80% of the binding energy of the substrate analogue inhibitors comes from the core sequence Phe-Arg-Ser which occurs between P2 and P1'. Molecular models developed from the Chen-Bode coordinates of the aprotinin-beta-PPK complex have been used to interpret the results of these studies. PMID- 1507199 TI - Synthesis and pharmacological evaluation of enantiomerically pure 4-deoxy-4 fluoromuscarines. AB - Four isomers of [(4-fluoro-5-methyl-tetrahydrofuran-2-yl)methyl]trimethylammonium iodide (4-deoxy-4-fluoro-muscarines) were prepared in enantiomerically and diastereomerically pure form from (S)-(-)-methyl 4-methylphenyl sulfoxide, ethyl fluoroacetate, and allyl bromide. Their absolute configurations were assigned by 1H NMR analyses. The four optically pure compounds were tested in vitro on guinea pig and their muscarinic potency was evaluated at M3 (ileum and bladder) and M2 (heart) muscarinic receptor subtypes. Compound 1a, the most potent isomer of the series, was also tested in vivo on pithed rat and its muscarinic activity at the M1 receptor subtype was compared with that of muscarine. Moreover, affinity and relative efficacy were calculated in vitro for this compound at M2 (heart force and rate) and M3 (ileum and bladder) receptors in order to investigate muscarinic receptor heterogeneity. The 4-deoxy-4-fluoromuscarines display a similar trend of potency as the corresponding muscarines and compound 1a shows differences in the affinity constants among the studied tissues. Replacement of a hydroxyl group for a fluorine atom in the 4 position of muscarine produces 1 order of magnitude increase in affinity for cardiac M2 muscarinic receptors controlling rate, while the affinity at cardiac M2 muscarinic receptors controlling force is unchanged, opening the possibility of a further classification of cardiac muscarinic receptors. PMID- 1507200 TI - 1,4-Dihydropyridines as antagonists of platelet activating factor. 1. Synthesis and structure-activity relationships of 2-(4-heterocyclyl)phenyl derivatives. AB - A novel class of 2-(4-heterocyclylphenyl)-1,4-dihydropyridines (2-38) possessing antagonist activity against platelet activating factor (PAF) was prepared by the Hantzsch synthesis from a variety of ethyl 4'-heterocyclic-substituted benzoylacetates, aryl or heteroaryl aldehydes, and substituted 3 aminocrotonamides or 3-aminocrotonate esters. Structure-activity relationships were evaluated where PAF antagonist activity was measured in vitro by determining the concentration of compound (IC50) required to inhibit the PAF-induced aggregation of rabbit washed platelets, and in vivo by determining the oral dose (ED50) which protected mice from a lethal injection of PAF. The nature of the substituent at the dihydropyridine 2-position was found to be important for both in vitro and in vivo activity, whereas there was greater flexibility for structural variation at the 4- and 5-positions. The most potent compound was 4-(2 chlorophenyl)-1,4-dihydro-3-(ethoxycarbonyl)-6-methyl-2-[4-(2- methylimidazo[4,5 c]pyrid-1-yl)phenyl]-5-[N-(2- pyridyl)carbamoyl]pyridine (17, UK-74,505), IC50 = 4.3 nM, ED50 = 0.26 mg/kg po, which was found to be approximately 33 times more potent in vitro (rabbit platelet aggregation) and about 8 times more potent in vivo (murine lethality) than WEB2086. Compound 17 also exhibited a long duration of action in the dog (inhibition of PAF-induced whole blood aggregation ex vivo was maintained for greater than 24 h following a single oral dose of 75 micrograms/kg) and was highly selective as a PAF antagonist, showing only weak affinity (IC50 = 6600 nM) for the [3H]nitrendipine binding site. As a result of its high oral potency, selectivity, and duration of action, UK-74,505 has been selected for clinical evaluation. PMID- 1507201 TI - Syntheses and affinities of novel organometallic-labeled estradiol derivatives: a structure-affinity relationship. AB - Two series of novel estradiol derivatives, including cationic species, labeled with organometallic fragments Cr(CO)3, Cp*Ru+, or Cp*Rh2+ [Cp* = eta 5-C5(CH3)5] either in the 17 alpha-position or on the A-ring were synthesized, and their relative binding affinities (RBA) for the estradiol receptor were determined. The Ru(II) and the Rh(III) cationic derivatives were obtained as stable salts with the following counter anions (BF4-, PF6-, CF3SO3-). The satisfactory RBA values obtained for most complexes belonging to the 17 alpha series confirm that this position tolerates the presence of bulky neutral species. For instance, complex 4, in which the organometallic fragment Cr(CO)3 was attached to the phenyl ring of the 17 alpha-phenylethynyl fragment, exhibited an RBA value of 24%, very similar to that of the uncomplexed estrogen derivative 3. Surprisingly, the analogous cationic species 6 had no affinity for the estradiol receptor. This unprecedented result shows that the hormone binding site of the estrogen receptor does not tolerate the presence of a positive charge in the 17 alpha-position of the steroid. On the other hand, the alpha-face of the A-ring of estradiol did tolerate positively charged organometallic fragments bearing bulky substituents although the RBA value tended to decrease with increasing charge. The counterion in these cationic derivatives also affected binding affinity. For instance, the Ru(II) species 7a containing an CF3SO3- ion exhibited a reasonable RBA value (5.8%) compared to analogous species 13 with a PF6- ion (RBA of only 0.1%). Moreover, the triflate counteranion preserved the phenolic form of the A-ring of the estrogen derivative whereas the PF6- derivative was unstable and rapidly converted into the dienonylic form in buffer. The compared RBAs of the neutral and cationic species illustrate the preferences of the receptor hormone binding site in accepting or rejecting species of hydrophobic or hydrophilic character. PMID- 1507202 TI - Synthetic nonpsychotropic cannabinoids with potent antiinflammatory, analgesic, and leukocyte antiadhesion activities. AB - Two strategies for the design of therapeutically useful cannabinoids have been combined to produce compounds with greatly increased antiinflammatory activity and with a low potential for adverse side effects. Enantiomeric cannabinoids with a carboxylic acid group at position 7 and with an elongated and branched alkyl sidechain at position 5' have been synthesized and tested for antiinflammatory activity. They were effective when given orally at doses of 10 micrograms/kg in reducing paw edema in mice that had been induced by either arachidonic acid or platelet activating factor. Leukocyte adhesion to culture dishes was also reduced in peritoneal cells from mice in which the cannabinoids were orally administered in the same dose range as for the paw edema tests. Antinociception could be observed in the mouse hot plate assay; however, little stereochemical preference was seen in contrast to the above tests where the 3R,4R compounds are more active than the 3S,4S enantiomers. Finally, in agreement with earlier reports on the naturally occurring pentyl side chain acids, the synthetic acids showed little activity in producing catalepsy in the mouse, suggesting that they would be nonpsychotropic in humans. PMID- 1507203 TI - Synthesis and cholinergic properties of N-aryl-2-[[[5-[(dimethylamino)methyl]-2 furanyl]methyl]thio]ethylamino analogs of ranitidine. AB - A series of N-aryl-2-[[[5-[(dimethylamino)methyl]-2- furanyl]methyl]thio]ethylamino analogs of the H2-antagonist, ranitidine, was synthesized and the abilities of the compounds to alleviate the cholinergic deficit characteristic of Alzheimer's disease evaluated. The compounds were initially tested for their ability to inhibit human erythrocyte acetylcholinesterase activity in vitro. Selected compounds were further evaluated for butyrylcholinesterase inhibition, M1 and M2 cholinergic receptor binding, potentiation of ileal contractions, and the ability to elevate brain acetylcholine levels in mice. The analogs were compared to tetrahydroaminoacridine and to a recently reported series of bis [[(dimethylamino)methyl]furans]. The N-aryl-2-[[[5-[(dimethylamino)methyl]-2- furanyl]methyl]thio]ethylamine derivatives were generally comparable to tetrahydroaminoacridine and the bis[[(dimethylamino)methyl]furans] in acetylcholinesterase inhibition, M1/M2 receptor binding, and the potentiation of ileal contractions, while being more potent inhibitors of acetylcholinesterase than butyrylcholinesterase. The 4-nitro-3-pyridazinyl analog, 26, was notable in demonstrating a potent and selective binding to the M2 receptor, with an M2 IC50/M1 IC50 of 0.060. Compounds in which the substituents on the dinitro-N-aryl moiety were relatively small were the best at inhibiting acetylcholinesterase in vitro. The N-aryl-2-[[[5-[(dimethylamino)methyl]-2- furanyl]methyl]thio]ethylamines in general, and those with small N-aryl substituents in particular, were superior to the bis[[(dimethylamino)methyl]furans] in elevating brain ACh levels in mice, probably due to enhanced distribution into the CNS. The 1,5-difluoro-2,4 dinitrophenyl analog, 8, resulted in the largest elevation in brain acetylcholine levels, affording a 53% increase at 88 mg/kg. PMID- 1507205 TI - S-(5'-deoxy-5'-adenosyl)-1-ammonio-4-(methylsulfonio)-2-cyclopentene: A potent, enzyme-activated irreversible inhibitor of S-adenosylmethionine decarboxylase. AB - The compound S-(5'-deoxy-5'-adenosyl)-1-ammonio-4-(methylsulfonio)-2- cyclopentene (AdoMac) was prepared and evaluated as an irreversible inhibitor of S-adenosylmethionine decarboxylase (AdoMet-DC). AdoMac was shown to inhibit AdoMet-DC in a time-dependent manner with a KI of 18.3 microM and a kinact of 0.133 min-1. In addition, AdoMet-DC activity could not be restored following extensive dialysis of the enzyme-inhibitor complex, and the enzyme was protected from irreversible inactivation by the known competitive inhibitor methylglyoxal bis(guanylhydrazone). HPLC analysis of the enzymatic reaction products revealed a time-dependent decrease in the peak coeluting with AdoMac, and a corresponding increase in the peak coeluting with (methylthio)adenosine (MTA), a byproduct of the irreversible binding of AdoMac to the enzyme. Thus, AdoMac appears to function as an enzyme-activated, irreversible inhibitor of AdoMet-DC. PMID- 1507204 TI - Novel 1-(pyridylphenyl)-1-phenyl-2-imidazolylethanols with topical antiinflammatory activity. AB - The synthesis, biological evaluation, and structure-activity relationships of a series of 1-(pyridylphenyl)-1-phenyl-2-imidazolylethanols are described. These compounds show potent dose-dependent topical antiinflammatory activity in murine models of skin inflammation. This effect is likely due to inhibition of cytochrome P450 and consequent reduction in levels of 12R-HETE in the skin. These compounds were examined for their ability to inhibit the oxidative metabolism of arachidonic acid; they specifically inhibit the formation of prostacyclins in mouse macrophages. To study the effects of structure on the in vivo activity, three general features of the molecules were varied: the position of attachment of the pyridine nucleus (A), the second aromatic residue (B), and the nitrogen base on the ethanol chain (C). 1-[4-(4-Pyridyl)phenyl]-1-(4-fluorophenyl)-2- imidazolylethanol (2a, DuP 983) shows a very attractive profile of antiinflammatory activity and has been selected for clinical evaluation as a topical antiinflammatory agent. PMID- 1507206 TI - Application of neural networks: quantitative structure-activity relationships of the derivatives of 2,4-diamino-5-(substituted-benzyl)pyrimidines as DHFR inhibitors. AB - A comparative study of quantitative structure-activity relationships involving diaminopyrimidines as DHFR inhibitors using regression analysis and the neural network approach suggests that the neural network can outperform traditional methods. The technique permits the highlighting the functional form of those parameters which have an influence on the biological activity. PMID- 1507207 TI - Hypoxia-selective antitumor agents. 5. Synthesis of water-soluble nitroaniline mustards with selective cytotoxicity for hypoxic mammalian cells. AB - Nitroaniline mustards have potential as hypoxia-selective cytotoxic agents, with reductive metabolism activating the nitrogen mustard by converting the electron withdrawing nitro group to an electron-donating hydroxylamine or amine. However, the parent compounds have poor aqueous solubility, and their potencies are limited by low reduction potentials (E1/2 ca. -600 mV versus the normal hydrogen electrode) and corresponding slow rates of nitro reduction. To address these limitations, a series of 4-nitroaniline mustards bearing hydrophilic side chains attached via an electron-withdrawing carboxamide group was prepared and evaluated for hypoxia-selective cytotoxicity against Chinese hamster cell lines. The N [(N,N-dimethylamino)ethyl]carboxamide derivatives proved to have excellent aqueous solubility and improved cytotoxic potency, but their reduction potentials, while higher than the non-carboxamide compounds, were still low and little selectivity for hypoxic cells were observed. A series of carboxamides of 2,4-dinitroaniline mustard was also prepared. These compounds had reduction potentials in the desired range (E1/2 ca. -450 mV by cyclic voltammetry) and were more toxic to hypoxic than aerobic UV4 cells. The most selective compounds were 5 [N,N-bis(2-chloroethyl)amino]-2,4-dinitrobenzamide (20, SN 23862) and its water soluble N-[(N,N-dimethylamino)ethyl]carboxamide analogue. These showed selectivities of 60- to 70-fold for hypoxic UV4 cells. The selectivity of 20 was much superior to that of its aziridine analogue (23, CB 1954), which was only 3.6 fold more toxic to hypoxic than oxic cells in the same system. Compound 20 is a much less efficient substrate than CB 1954 for the major aerobic nitroreductase from rat Walker tumor cells, NAD(P)H:quinone oxidoreductase (DT diaphorase). Lack of aerobic bioactivation of 20 by DT diaphorases may be responsible for its higher hypoxic selectivity than that of 23. PMID- 1507208 TI - Synthesis and antiviral evaluation of N-carboxamidine-substituted analogues of 1 beta-D-ribofuranosyl-1,2,4-triazole-3-carboxamidine hydrochloride. AB - Ten, hitherto unreported, analogues of 1-beta-D-ribofuranosyl-1,2,4-triazole-3 carboxamidine hydrochloride (2a, ribamidine) and methyl carboximidate 5 have been synthesized. These include the N-cyano (2b), N-alkyl (2c-e), N-amino acid (2f-h), N,N'-disubstituted (6, 7a,b), and the N-methylated carboxamide (1f) analogues of ribavirin. In addition, a new facile synthesis of carboxamidine 2a was also developed. All compounds were evaluated for biological activity against the following RNA viruses: Punta Toro (PT) and sandfly fever (SF) viruses (bunyaviruses); Japanese encephalitis (JE), yellow fever (YF), and dengue-4 viruses (flaviviruses); parainfluenza type 3 (PIV3), respiratory syncytial virus (RSV), and measles viruses (paramyxoviruses); influenza A and influenza B viruses (orthomyxoviruses); Venezuelan equine encephalomyelitis virus (VEE, alphavirus); human immunodeficiency virus type-1 (HIV-1, lentivirus); the DNA-containing vaccinia (VV) virus (poxvirus); and adeno type 5 (Ad5) viruses. All of the compounds except for 2b and 7a,b exhibited activity against the bunyaviruses such as that observed with 2a; however, higher IC50 values were generally observed. Glycine analogue 2f showed activity in PT-virus-infected mice in terms of increased survivors and decreased markers of viral pathogenicity. Carboxamidine 2a, carboximidate 5, and dimethyl amidine 6 exhibited activity against dengue type-4 virus. Monomethyl amidine 2c demonstrated activity against RSV, PIV3, and, to a lesser extent, influenza A and B. Activity of 2c generally required higher IC50 values than unsubstituted 2a. The latter exhibited hitherto unreported activity against RSV; therapeutic indices for 2a against RSV and PIV3 were greater than 64 and greater than 21. No substantial in vitro activity was observed for any of the compounds tested against Ad5, measles, JE, YF, VEE, or HIV-1. In addition, evidence is presented which argues in favor of a distinct antiviral mechanism of action for carboxamidines, e.g. 6, in contrast to a role as a carboxamide precursor. PMID- 1507209 TI - Histamine H2-receptor agonists. Synthesis, in vitro pharmacology, and qualitative structure-activity relationships of substituted 4- and 5-(2-aminoethyl)thiazoles. AB - It is well known that both histamine and dimaprit show moderate histamine H2 receptor agonistic activities on the guinea pig right atrium. Quantum chemical calculations on these two compounds showed similarities in electron distributions and molecular electrostatic potentials (MEP's), which could be extended to rigid analogues [2-amino-5-(2-aminoethyl)thiazoles] of the latter structure. On the base of these results a series of substituted 4- and 5-(2-aminoethyl)thiazoles was synthesized applying small alkyl substitution variations as reported for histamine. 2-Amino-5-(2-aminoethyl)-4-methylthiazole (Amthamine) proved to be the most potent full histamine H2-receptor agonist on the guinea pig right atrium, being with a pD2 value of 6.21 slightly more potent than histamine. This compound shows no affinity for H1-receptors and is a full but weak agonist on the histamine H3-receptor with a pD2 value of 4.70, thus showing a marked specificity for histamine H2-receptors. In the 5-(2-aminoethyl)thiazole series the presence of a 2-amino substituent proved to be not essential for stimulation of the histamine H2-receptor, leading to the important conclusion that in contrast to histamine, for this series, acceptance of a proton by the thiazole nucleus of the agonist from the active site of the receptor is sufficient for the stimulation of the histamine H2-receptor. PMID- 1507210 TI - Synthesis, characterization, and Ca2+ antagonistic activity of diltiazem metabolites. AB - Diltiazem is a calcium antagonist widely used in the treatment of angina and hypertension. The contributions of metabolites of diltiazem to the vasorelaxant effects of diltiazem were investigated. The synthesis and spectroscopic characterization of eight major cis-diltiazem metabolites are described. Three of the compounds--N, O-didemethylated metabolite (21), O-demethylated metabolite (22), and diltiazem N-oxide (27)--have been recently reported and have not previously been synthesized. The identities of all eight synthetic metabolites have been verified with samples obtained from human urine using combined LC MS/MS. The Ca2+ antagonistic activities of diltiazem and its metabolites (except 27) were studied on hamster aorta preparations depolarized with KCl. The order of potencies (IC50 +/- SE, microM) is as follows: diltiazem (0.98 +/- 0.47) greater than 17 (2.46 +/- 0.38) greater than or equal to 23 (3.27 +/- 1.02) greater than 26 (20.2 +/- 10.5) greater than 22 (40.4 +/- 15.4) greater than or equal to 25 (45.5 +/- 18.1) greater than 21 (112.2 +/- 33.2) greater than or equal to 24 (126.7 +/- 24.2). Structure-activity relationships are also discussed. PMID- 1507211 TI - Conformationally restrained, chiral (phenylisopropyl)amino-substituted pyrazolo[3,4-d]pyrimidines and purines with selectivity for adenosine A1 and A2 receptors. AB - Two modes of tethering a chiral (phenylisopropyl)amino substituent in pyrazolo[3,4-d]pyrimidines and purines have been explored. One mode gave (S)-2,7 dihydro-7-phenyl-2-(phenylmethyl)-5- propoxy-3H-imidazo[1,2-c]pyrazolo-[4,3 e]pyrimidine (12a) and its corresponding R-enantiomer 12b, which were selective for A2 and A1 adenosine receptors, respectively. The corresponding diimidazo[1,2 c:4',5'-e]pyrimidines 12e and 12f were analogously selective. This is the first example where a single chiral recognition unit provides enantiomers with opposite selectivities for adenosine receptors. The second mode gave (2S-trans)-2,7 dihydro-2-methyl-3,7-diphenyl-5- propoxy-3H-imidazo[1,2-c]-pyrazolo[4,3 e]pyrimidine (12c) and its corresponding R-enantiomer 12d. Compounds 12c and 12d were significantly less potent than 12a and 12b at A1 receptors, and were nonselective. PMID- 1507212 TI - Urea and 2-imidazolidone derivatives of the muscarinic agents oxotremorine and N methyl-N-(1-methyl-4-pyrrolidino-2-butynyl)acetamide. AB - Some urea and 2-imidazolidone analogues of the muscarinic agents oxotremorine (1) and N-methyl-N-(1-methyl-4-pyrrolidino-2-butynyl)acetamide [10; BM-5] have been synthesized and assayed for muscarinic and antimuscarinic activity on the isolated guinea pig ileum. The new compounds (15-24) were found to be muscarinic agonists, partial agonists, or antagonists. The compounds were also tested for in vitro receptor binding to homogenates of the rat cerebral cortex using the muscarinic antagonist [3H]-3-quinuclidinyl benzilate ([3H]QNB) as the ligand. They were found to be less potent than 1 in this assay. On the guinea pig ileum, the N-3-methyl substituted imidazolidone analogue 20 was the most potent agonist of the new compounds studied; 20 was 5-fold more potent in inducing contractions of the ileum and had 4-fold higher affinity for ileal muscarinic receptors than the 3-methyl substituted 2-pyrrolidone 6. However, the N-3-unsubstituted urea and imidazolidone derivatives 15 and 19 were several-fold less potent than the parent acetamide N-methyl-N-(4-pyrrolidino-2-butynyl)acetamide [9; UH-5] and 1, respectively. The urea analogue (16) of the partial muscarinic agonist 10 was devoid of intrinsic activity and displayed 3-fold lower affinity than 10 for ileal muscarinic receptors. PMID- 1507213 TI - Time-dependent inhibition of human placental aromatase with a 2,19-methyleneoxy bridged androstenedione. PMID- 1507214 TI - Accessibility to primary care in Mississippi. PMID- 1507215 TI - Mississippi Comprehensive Health Insurance Risk Pool Association. PMID- 1507216 TI - Terminal disorder: a common structural feature of the axial proteins of bacterial flagellum? AB - We report, based on proteolytic experiments and high resolution 1H nuclear magnetic resonance studies that the terminal regions of the monomeric hook protein are highly mobile and exposed to the solvent. The disordered parts of the hook protein span approximately the first 70 and the last 30 amino acid residues. Although the amino acid sequences of flagellin and hook protein do not resemble each other at all, both proteins have now been shown to contain large disordered terminal regions. Sequential similarities of flagellin and hook protein, especially near the NH2 and COOH termini, to other axial components of bacterial flagellum suggest that terminal disorder may be a common structural feature of the axial proteins of the bacterial flagellum. PMID- 1507217 TI - Interdependence of translation, transcription and mRNA degradation in the lacZ gene. AB - We have constructed a collection of Escherichia coli strains which differ by point mutations in the ribosome binding site (RBS) that drives the translation of the lacZ gene. These mutations affect the Shine-Dalgarno sequence or the initiation codon, or create secondary structures that sequester these elements, and result in a 200-fold variation in beta-galactosidase expression. Surprisingly, these variations of expression are paralleled by nearly equivalent changes in the lacZ mRNA level. The ratio of the beta-galactosidase expression to the mRNA level reflects the average spacing between translating ribosomes: hence, paradoxically, mutations that affect translation initiation do not correspondingly change this spacing. Further analysis of the mRNA level variations shows that they originate from two independent mechanisms. When beta galactosidase expression exceeds a threshold corresponding roughly to one translation event per transcript, the variations in the efficiency of translation initiation affect largely the chemical and functional lifetimes of the mRNA. We further show that the rate-limiting step in the chemical decay process is an RNase E-dependent cleavage, which is outcompeted by translation initiation. Below this expression threshold, the mRNA lifetime levels out and strain-to-strain variations in mRNA level arise solely from polarity effects. We suggest that, in this activity range, most mRNA molecules that escape polarity are crossed by a single ribosome, and hence are identical from the viewpoint of degradation. Altogether, the tight couplings between translation initiation on one hand, polarity and/or mRNA degradation on the other, result in translation initiation events being closely spaced in time even from inefficient RBS, at the expense of the mRNA level. Finally, we evocate the possible beneficial consequences of a coupling between translation, transcription and mRNA degradation, for the management of cellular resources. PMID- 1507218 TI - Culture conditions differentially affect the translation of individual Escherichia coli mRNAs. AB - Our aim is to investigate whether changes in growth conditions can differentially affect the initiation of translation from individual Escherichia coli mRNAs that are not subjected to specific translational control. As a model system, we have constructed a series of point-mutated lacZ genes which differ in their Shine Dalgarno (SD) sequence, their initiator codon, or the secondary structure around these elements. Alterations in growth conditions produced large (up to 8-fold) changes in the relative expression from these genes, which, we argue, stem from changes in their relative efficiencies of translation initiation. In particular, compared to genes bearing mutations outside the SD or initiator codon, genes mutated in these elements experience a significant decrease in their expression when cells are grown in minimal rather than rich medium; at 42 degrees C rather than 37 degrees C; or under amino acid starvation. We discuss the mechanisms underlying these effects, and evocate their possible generality. PMID- 1507219 TI - Translation inhibition by an mRNA coding region secondary structure is determined by its proximity to the AUG initiation codon. AB - In the present study we investigate the impact of highly stable coding region secondary structures on mRNA translation efficiency. By introducing antisense segments into the 3'non-translated region of human alpha-globin mRNA we are able to synthesize a series of transcripts in which site-specific secondary structures are introduced without altering the primary structure of the 5' non-translated region, the coding region, or the encoded protein product. Coding region duplexes in close proximity to the AUG initiation codon are found to inhibit translation severely to a degree equal to that of a duplex that extends into the 5' non translated region. In contrast, mRNAs containing duplexes positioned further 3' in the coding region translate at levels that are significantly higher although are still below those of native alpha-globin mRNA. The primary determinant of translation inhibition by coding region duplexes appears to be the proximity of the duplex to the AUG initiation codon and reflects a parallel inhibition of monosome formation. These data demonstrate that extensive coding region secondary structures suppress translation to a minimal or to a substantial degree depending on their distance from the initiation codon. PMID- 1507220 TI - Functional structures of the recA protein found by chimera analysis. AB - We developed a novel genetic method for finding functional regions of a protein by the analysis of chimeras formed between homologous proteins. Sets of chimeric genes were made by intramolecular homologous recombination in a linearized plasmid DNA carrying both recA genes of Escherichia coli and Pseudomonas aeruginosa. A recBCsbcA strain of E. coli was used for isolation of plasmids carrying recombinants between these genes. Examination of properties of E. coli strains deleting the recA gene and carrying a plasmid with a chimeric gene shows that chimera formation at certain positions inactivates a RecA function. Frequently, all chimeras with a junction in a certain region of the protein inactivate a function. Rather than a direct effect of the presence of the junction at a particular position, mismatching of the regions both sides of the junction that are derived from the different species is responsible for the inactivation. For a chimeric protein to be functional, certain pairs of sequences in different regions of the protein must derive from the same parent. Four pairs of such sequences were found: two are involved in activities for genetic recombination and for resistance to ultraviolet light irradiation and the others in formation of active oligomers. Regions defined by these sequences are located in the looped regions of the protein. A pair of regions may co-operate to form a functional folded structure. PMID- 1507221 TI - Alu RNA transcripts in human embryonal carcinoma cells. Model of post transcriptional selection of master sequences. AB - Alu master sequences colonized the human genome using RNA as amplification intermediate. To understand this phenomenon better we isolated and analyzed Alu RNA from NTera2D1 pluripotential cells. Northern hybridization, primer extension, cDNA cloning and sequencing data are congruent and demonstrate a low level of Alu specific transcription. These bona fide RNA Polymerase III Alu transcripts, although enriched in the cytoplasm, are not dominated by a single master species but rather originate from a variety of loci. However, when compared with the genomic average, or to repeats from RNA Polymerase II co-transcripts, they belong to the youngest group of Alu subfamilies (p less than 0.001) and have a higher content of intact CpG-dinucleotides. This suggests that Alu transcription is influenced both by mutations and the genomic context, and points to a possible role of DNA methylation in silencing the bulk of genomic repeats. Because of the heterogeneity of Alu transcripts a post-transcriptional selection mechanism recruiting Alu master sequences for retroposition is required. We propose that Alu RNA masters could have evolved as selfish satellites to a more complex retroposition system equipped with a reverse transcriptase activity and that their structure was conserved through "phenotypic" selection of the RNA level. PMID- 1507222 TI - Activation of recA protein. The open helix model for LexA cleavage. AB - RecA protein is induced by the binding of DNA and ATP to become active in the hydrolysis of ATP and the cleavage of repressors. These reactions appear to depend on the structural state of the protein polymerized along the DNA, i.e. a helical coat of six RecA per turn of 95 to 100 A pitch. In support of this model of the active conformation, it was shown that high concentrations of salt also induce this helical polymerized state as well as the enzymatic activities. Here, we describe that, in vitro and with the non-hydrolyzable analogue ATP gamma S, RNA and heparin can also induce both the structural transition and the enzymatic activation of RecA to LexA cleavage in accordance with the model. RNA and heparin do not support the reaction in the presence of ATP, and they do not induce the hydrolysis of ATP either, suggesting that, in contrast to ATP gamma S, the nucleotide is not bound stably enough, and that the combined affinities of polynucleotide and ATP actually modulate the discrimination of RecA for the various possible inducers in vivo. PMID- 1507223 TI - Association of AUUUA-binding protein with A+U-rich mRNA during nucleo-cytoplasmic transport. AB - Resealed nuclear envelope (NE) vesicles from rat liver containing entrapped exogenous RNA were used to study the effect of adenosine+uridine binding factor (AUBF), present in cytosolic cell extracts, on ATP-dependent transport of A+U rich RNA (AU+RNA) and A+U-free RNA (AU-RNA) across the NE. This factor specifically binds to A+U-rich sequences present in the 3' untranslated regions of lymphokine and cytokine mRNAs, containing overlapping AUUUA boxes (granulocyte macrophage colony stimulating factor, interleukin-3). Addition of AUBF to the extravesicular compartment markedly increased the efflux of the in vitro transcribed, capped and polyadenylated AU+ RNAs. Export of entrapped AU- control RNA, such as beta-globin RNA, was not affected by AUBF, in contrast to chimeric AU+ beta-globin RNA containing the A+U-rich sequence of human interferon-alpha mRNA (6 reiterated AUUUA motifs). Competition experiments revealed that AUBF enhances the affinity of poly(A)-containing AU+ RNAs to the NE poly(A)-binding component (poly(A)-recognizing mRNA carrier p106), and thereby accelerates nuclear export of these RNAs. We could demonstrate that AUBF added to the extravesicular space forms stable complexes with polyadenylated AU+ RNA with relative molecular masses of about 45,000, 62,000 and 70,000 inside the vesicles or during ATP-dependent export. In addition we determined that AUBF may affect mRNA stability by protecting A+U-rich RNA against degradation by trans-acting, nuclear matrix-associated and A+U-specific endoribonuclease V. PMID- 1507224 TI - The rhombotin gene family encode related LIM-domain proteins whose differing expression suggests multiple roles in mouse development. AB - The rhombotin (RBTN1 or Ttg-1) gene was first identified at a chromosome translocation in a T-cell acute leukaemia and later used to isolate two related genes (RBTN2 or Ttg-2 and RBTN3). Complete characterization of these genes in man and mouse shows that all three encode cysteine-rich proteins with typical LIM domains. RBTN1 and RBTN3-derived proteins have 98% identity in the LIM domains but are located on separate chromosomes in man and in mouse while RBTN1 and RBTN2, both located on human chromosome 11p but are on separate chromosomes in mouse, are only 48% identical in this part of the protein. The exon organization of RBTN1 and RBTN3 genes are similar, both having an intron, absent from the RBTN2 gene, in the LIM2-encoding region. The remarkable similarity between rbtn-1 and rbtn-3 proteins is parallelled in their expression patterns in mouse development, since both genes show high expression in restricted areas of the brain, but little lymphoid expression. rbtn-2 expression, however, is more ubiquitous. This gene shows a low level of thymus expression but high expression in fetal liver, adult spleen and B-cell lines, consistent with a role in B-cell development. These results suggest multiple cellular targets for the action of these proteins during development. PMID- 1507225 TI - Quantitation of molecular densities by cryo-electron microscopy. Determination of the radial density distribution of tobacco mosaic virus. AB - We have determined the absolute mass and radial scattering density distribution of tobacco mosaic virus in the frozen-hydrated state by energy-filtered low-dose bright-field transmission electron microscopy. The absolute magnitude of electron scattering from tobacco mosaic virus in 150 nm of ice was within 3.0% of that predicted, with inelastic scattering accounting for approximately 80% of the scattering contrast. In order to test the accuracy of the radial reconstruction, a computer model of tobacco mosaic virus was built from the atomic co-ordinates assuming uniform solvent density. The validity of the model was confirmed by comparison of X-ray scattering and predictions of the model (R factor = 0.05). First-order corrections for the microscope contrast transfer function were necessary and sufficient for conversion of the cryo-electron microscopy images into accurate representations of the mass density. At 1.9 nm resolution the compensated reconstruction and model had density peaks of similar magnitude at 2.4, 4.2, 6.0 and 7.8 nm radius and a central hole of 2 nm radius. Equatorial Fourier transforms of the corrected electron images were in excellent agreement with predictions of the model (R factor = 0.12). Thus, the uniform solvent approximation was adequate at 1.9 nm resolution to describe quantitatively X-ray scattering in liquid water and electron imaging in vitreous ice. This is the first demonstration that cryo-electron microscopy images can be used to quantitate the absolute mass, mass per unit length and internal density distributions of proteins and nucleic acids. PMID- 1507226 TI - Conformational sub-states in B-DNA. AB - Theoretical studies of the sequence-dependent conformation of B-DNA have been carried out using Jumna, a helicoidal co-ordinate minimization algorithm. The results obtained for a series of six oligomers with repetitive sequences show that, with the exception of the homopolymers (dA)n.(dT)n and (dG)n.(dC)n, all sequences can adopt a variety of conformations characterized by considerable changes in helicoidal parameters and also in sugar puckers which adopt C(2')-endo (falling into 2 classes) or, in the case of pyrimidine nucleotides, O(1')-endo forms. These studies lead to an improved understanding of the role of base sequence on DNA conformation and point to a number of interesting correlations between the various structural parameters describing the double helix. PMID- 1507228 TI - Folding of peptide fragments comprising the complete sequence of proteins. Models for initiation of protein folding. II. Plastocyanin. AB - In an attempt to understand the earliest events in the protein folding pathway, the complete sequence of French bean plastocyanin has been synthesized as a series of short peptide fragments, and the conformational preferences of each peptide examined in aqueous solution using proton n.m.r. methods. Plastocyanin consists largely of beta-sheet, with reverse turns and loops between the strands of the sheet, and one short helix. The n.m.r. experiments indicate that most of the peptides derived from the plastocyanin sequence have remarkably little propensity to adopt folded conformations in aqueous solution, in marked contrast to the peptides derived from the helical protein, myohemerythrin (accompanying paper). For most plastocyanin peptides, the backbone dihedral angles are predominantly in the beta-region of conformational space. Some of the peptides show weak NOE connectivities between adjacent amide protons, indicative of small local populations of backbone conformations in the a region of (phi,psi) space. A conformational preference for a reverse turn is seen in the sequence Ala65-Pro Gly-Glu68, where a turn structure is found in the folded protein. Significantly, the peptide sequences that populate the alpha-region of (phi,psi) space are mostly derived from turn and loop regions in the protein. The addition of trifluoroethanol does not drive the peptides into helical conformations. In one region of the sequence, the n.m.r. spectra provide evidence of the formation of a hydrophobic cluster involving aromatic and aliphatic side-chains. These results have significance for understanding the initiation of protein folding. From these studies of the fragments of plastocyanin (this paper) and myohemerythrin (accompanying paper), it appears that there is a pre-partitioning of the conformational space sampled by the polypeptide backbone that is related to the secondary structure in the final folded state. PMID- 1507227 TI - Folding of peptide fragments comprising the complete sequence of proteins. Models for initiation of protein folding. I. Myohemerythrin. AB - In an attempt to delineate potential folding initiation sites for different protein structural motifs, we have synthesized series of peptides that span the entire length of the polypeptide chain of two proteins, and examined their conformational preferences in aqueous solution using proton nuclear magnetic resonance and circular dichroism spectroscopy. We describe here the behavior of peptides derived from a simple four-helix bundle protein, myohemerythrin. The peptides correspond to the sequences of the four long helices (the A, B, C and D helices), the N- and C-terminal loops and the connecting sequences between the helices. The peptides corresponding to the helices of the folded protein all exhibit preferences for helix-like conformations in solution. The conformational ensembles of the A- and D-helix peptides contain ordered helical forms, as shown by extensive series of medium-range nuclear Overhauser effect connectivities, while the B- and C-helix peptides exhibit conformational preferences for nascent helix. All four peptides adopt ordered helical conformations in mixtures of trifluoroethanol and water. The terminal and interconnecting loop peptides also appear to contain appreciable populations of conformers with backbone phi and psi angles in the alpha-region and include highly populated hydrophobic cluster and/or turn conformations in some cases. Trifluoroethanol is unable to drive these peptides towards helical conformations. Overall, the peptide fragments of myohemerythrin have a marked preference towards secondary structure formation in aqueous solution. In contrast, peptide fragments derived from the beta-sandwich protein plastocyanin are relatively devoid of secondary structure in aqueous solution (see accompanying paper). These results suggest that the two different protein structural motifs may require different propensities for formation of local elements of secondary structure to initiate folding, and that there is a prepartitioning of conformational space determined by the local amino acid sequence that is different for the helical and beta-sandwich structural motifs. PMID- 1507229 TI - Modeling of the structure of bacteriorhodopsin. A molecular dynamics study. AB - Secondary structure predictions for membrane proteins are relatively reliable and permit the construction of model structures that may serve as initial conformations for molecular dynamics simulations. This might provide a scheme to predict the three-dimensional structures of membrane proteins. The feasibility of such an approach is tested for bacteriorhodopsin. We were not able to fully predict the kidney-shaped structure of bacteriorhodopsin. However, features compatible with this structure developed in a simulation starting from a circular arrangement of the seven predicted helices. When instead we started from the kidney shape, assigning the seven predicted helices in different ways to those on the structure, we could distinguish between the different assignments on the basis of energy and tilt of the helices. In this way we could select the correct assignment from a few others. For the correct assignment, the helices spontaneously adopted a tilt that agrees remarkably well with the experimental model structure derived by others. The root-mean-square deviation between our best molecular dynamics structure and the experimental model structure is 3.8 A, caused mainly by deviations in the internal degrees of freedom of the helices. PMID- 1507230 TI - Crystal structure of Escherichia coli malate dehydrogenase. A complex of the apoenzyme and citrate at 1.87 A resolution. AB - The crystal structure of malate dehydrogenase from Escherichia coli has been determined with a resulting R-factor of 0.187 for X-ray data from 8.0 to 1.87 A. Molecular replacement, using the partially refined structure of porcine mitochondrial malate dehydrogenase as a probe, provided initial phases. The structure of this prokaryotic enzyme is closely homologous with the mitochondrial enzyme but somewhat less similar to cytosolic malate dehydrogenase from eukaryotes. However, all three enzymes are dimeric and form the subunit-subunit interface through similar surface regions. A citrate ion, found in the active site, helps define the residues involved in substrate binding and catalysis. Two arginine residues, R81 and R153, interacting with the citrate are believed to confer substrate specificity. The hydroxyl of the citrate is hydrogen-bonded to a histidine, H177, and similar interactions could be assigned to a bound malate or oxaloacetate. Histidine 177 is also hydrogen-bonded to an aspartate, D150, to form a classic His.Asp pair. Studies of the active site cavity indicate that the bound citrate would occupy part of the site needed for the coenzyme. In a model building study, the cofactor, NAD, was placed into the coenzyme site which exists when the citrate was converted to malate and crystallographic water molecules removed. This hypothetical model of a ternary complex was energy minimized for comparison with the structure of the binary complex of porcine cytosolic malate dehydrogenase. Many residues involved in cofactor binding in the minimized E. coli malate dehydrogenase structure are homologous to coenzyme binding residues in cytosolic malate dehydrogenase. In the energy minimized structure of the ternary complex, the C-4 atom of NAD is in van der Waals' contact with the C-3 atom of the malate. A catalytic cycle involves hydride transfer between these two atoms. PMID- 1507231 TI - Structure-function relationships in the low-affinity mutant haemoglobin Aalborg (Gly74 (E18)beta----Arg). AB - Haemoglobin Aalborg (Gly74 (E18)beta----Arg) has a reduced oxygen affinity, in both the absence and the presence of organic phosphates; it has a raised affinity for organic phosphates, and it is moderately unstable. By contrast, haemoglobin Shepherds Bush (Gly74 (E18)beta----Asp) has an increased oxygen affinity in both the absence and the presence of organic phosphates, a diminished affinity for organic phosphates and is also unstable. We have determined the crystal structure of deoxyhaemoglobin Aalborg at 2.8 A resolution and compared it to the structures of deoxy- and oxyhaemoglobin A and of deoxyhaemoglobin Shepherds Bush. The guanidinium group of Arg74(E18)beta protrudes from the haem pocket and donates hydrogen bonds to the E and F helices. The carboxylate group of Asp74(E18)beta forms a hydrogen bond only with residue EF6 and is partially buried, which may be why haemoglobin Shepherds Bush appears to be more unstable than haemoglobin Aalborg. To discover why the latter has a low oxygen affinity, we superimposed the B, G and H helices of haemoglobin A, whose conformation is known to be unaffected by ligand binding, on those of haemoglobin Aalborg. This also brought helices E and the haems into superposition, but revealed a shift of the F helix of deoxyhaemoglobin Aalborg towards the EF-corner. This shift is opposite to that which occurs on ligand binding and on transition to the quaternary oxy-structure, and is linked to an increased tilt of the proximal histidine residue away from the haem axis. Since the relative positions of helices E and F and of the haem group are thought to be the main determinants of the changes in oxygen affinity, the shift of helix F may account for the reduced oxygen affinity of haemoglobin Aalborg. The shift may be due to a combination of steric and electrostatic effects introduced by the arginine residue's side-chain. The effects of the arginine and aspartate substitutions at position E18 beta on the 2,3 diphosphoglycerate affinity are equal and opposite. They can be quantitatively accounted for by the electrostatic attraction or repulsion by the oppositely charged side-chains. PMID- 1507233 TI - Crystallization of recombinant chitinase from the cloned chiA gene of Serratia marcescens. AB - The chiA gene encoding for the chitinase enzyme from Serratia marcescens was efficiently overexpressed under the pL promoter and the enzyme was secreted into the growth medium. The chitinase was purified to homogeneity using affinity chromatography on a Phenyl-Sepharose column and the protein was successfully crystallized. The crystals are presently in the form of small needles in space group C222(1) and have unit cell dimensions a = 204(+/- 0.5) A, b = 134(+/- 0.5) A, c = 60(+/- 0.5) A. The crystals diffract X-rays to about 3 A resolution and are suitable for three-dimensional structural analysis. PMID- 1507232 TI - Selection of phage antibodies by binding affinity. Mimicking affinity maturation. AB - We describe a process, based on display of antibodies on the surface of filamentous bacteriophage, for selecting antibodies either by their affinity for antigen or by their kinetics of dissociation (off-rate) from antigen. For affinity selection, phage are mixed with small amounts of soluble biotinylated antigen (less than 1 microgram) such that the antigen is in excess over phage but with the concentration of antigen lower than the dissociation constant (Kd) of the antibody. Those phage bound to antigen are then selected using streptavidin coated paramagnetic beads. The process can distinguish between antibodies with closely related affinities. For off-rate selection, antibodies are preloaded with biotinylated antigen and diluted into excess unlabelled antigen for variable times prior to capture on streptavidin-coated paramagnetic beads. To mimic the affinity maturation process of the immune system, we introduced random mutations into the antibody genes in vitro using an error-prone polymerase, and used affinity selection to isolate mutants with improved affinity. Starting with a small library (40,000 clones) of mutants (average 1.7 base changes per VH gene) of the mouse antibody B1.8, and using several rounds of affinity selection, we isolated a mutant with a fourfold improved affinity to the hapten 4-hydroxy-5 iodo-3-nitrophenacetyl-(NIP)-caproic acid (mutant Kd = 9.4(+/- 0.3) nM compared with B1.8 Kd = 41.9(+/- 1.6) nm). The relative increase in affinity of the mutant is comparable to the increase seen in the anti-4-hydroxy-3-nitrophenylacetyl/NIP caproic acid murine secondary immune response. PMID- 1507234 TI - Sequence of lamprey vitellogenin. Implications for the lipovitellin crystal structure. AB - The amino acid sequence of lamprey vitellogenin has been predicted from the nucleotide sequence of cloned cDNA. The sites of proteolytic cleavage that produce the lipovitellin complex from the vitellogenin have been located by comparing the N-terminal sequences of two lamprey lipovitellin polypeptides with the predicted sequence. These results also confirm that the vitellogenin sequence derived here corresponds to the lipovitellin complex for which the crystal structure has been solved previously. Predictions of secondary structure indicate that the region most likely to correspond to the large alpha-helical domain of the crystallographic model consists of vitellogenin residues 300 to 600. Similar to the lipovitellins of Xenopus laevis, lamprey lipovitellin appears to lack approximately 200 C-terminal residues that are present in vitellogenin. However, the lamprey lipovitellin differs from those of Xenopus and chicken in two respects. First, most of the serine-rich domain that is present as the phosvitin polypeptide in the lipovitellins of the higher vertebrates appears to be lost in the maturation of lamprey vitellogenin to lipovitellin. Second, the domains that constitute the large lipovitellin-1 polypeptide in Xenopus and chicken are present in two polypeptides in lamprey, owing to an additional proteolytic processing event. PMID- 1507235 TI - N-methyl-N-nitrosourea-induced mutations in human cells. Effects of the transcriptional activity of the target gene. PMID- 1507236 TI - Histology of the esophagus of the adult frog Rana perezi (Anura: Ranidae). AB - Study of the esophageal microscopic morphology of adult Rana perezi by light and electron microscopy discloses some large folds throughout the esophagus that are in themselves ringed. Glandular ostia open in the furrows of the luminal surface. The esophageal wall is made up of a connective adventitia rich in melanocytes, a muscular tunica, a connective and glandular subepithelial layer, and a pseudostratified ciliated epithelium. This epithelium basically consists of ciliated, goblet, basal, microvillous-apex, and migratory cells. Two types of goblet cells are distinguished with regard to the granular ultrastructure. The microvillous-apex cell has not been found in other amphibians. It shows a very differentiated morphology with a high number of mitochondria. The basal cells give the epithelium a pseudostratified morphology, and they have a proliferative function. Glands are branched and drain through an excretory duct that has a monolayered mucosecreting epithelium. The glandular units are formed by two principal types of cells: mucosecretory and serous. PMID- 1507237 TI - Electron microscopic structure and innervation of the carotid baroreceptor region in the rock hyrax (Procavia capensis). AB - Semi-thin plastic sections reveal that the carotid baroreceptor region in the rock hyrax comprising the origin of the internal carotid artery has a preponderantly elastic structure and a thick tunica adventitia. In contrast, the common carotid artery has a musculoelastic structure, whereas the cranial segment of the internal carotid artery (immediately distal to the baroreceptor areas) shows the features of a muscular artery. Electron microscopy discloses the presence of sensory nerve endings within the parts of the tunica adventitia adjoining the preponderantly elastic zone of the internal carotid artery. These nerve endings are characterized by varicose regions containing a large quantity of mitochondria. Bundles of collagen fibers in the tunica adventitia form convolutions or whorls around the nerve terminals and often terminate on the surface of the elastic fibers or into the basement membranes of the neuronal profiles. The large content of elastic tissue in the tunica media of the baroreceptor region may render the vessel wall highly distensible to intraluminal pressure changes. This, in turn, would facilitate the transmission of the stimulus intensity to the sensory nerve terminals located in the tunica adventitia. It is suggested that the stretching of elastic fibers may form the main mechanical event leading to the distortion of the associated nerve terminals. However, a change in the geometrical configuration of the bundles of collagen under the influence of the elastic fibers may provide a better insight into the mechanisms of distortion of the baroreceptors related to and/or in contact with collagen fibers. PMID- 1507238 TI - Edgeworth's legacy of cranial muscle development with an analysis of muscles in the ventral gill arch region of batoid fishes (Chondrichthyes: Batoidea). AB - A series of studies by Edgeworth demonstrated that cranial muscles of gnathostome fishes are embryologically of somitic origin, originating from the mandibular, hyoid, branchial, epibranchial, and hypobranchial muscle plates. Recent experimental studies using quail-chick chimeras support Edgeworth's view on the developmental origin of cranial muscles. One of his findings, the existence of the premyogenic condensation constrictor dorsalis in teleost fishes, has also been confirmed by molecular developmental studies. Therefore, developmental mechanisms for patterning of cranial muscles, as described and implicated by Edgeworth, may serve as structural entities or regulatory phenomena responsible for developmental and evolutionary changes. With Edgeworth's and other studies as background, muscles in the ventral gill arch region of batoid fishes are analyzed and compared with those of other gnathostome fishes. The spiracularis is regarded as homologous at least within batoid fishes, but its status within elasmobranchs remains unclear; developmental modifications of the spiracularis proper are evident in some batoid fishes and in several shark groups. The peculiar ventral extension of the spiracularis in electric rays and some stingrays may represent convergence, probably facilitating ventilation and/or feeding in both groups. The evolutionary origin of the "internus" and "externus" remains uncertain, despite the fact that a variety of forms of the constrictor superficiales ventrales in batoid fishes indicates an actual medio-ventral extension of the "externus." The intermandibularis is probably present only in electric rays. The "X" muscle occurs only in electric rays and is considered to be Edgeworth's intermandibularis profundus. Its association with the adductor mandibular complex in narkinidid and narcinidid electric rays may relate to its functional role in lower jaw movement. Contrary to common belief, in most batoid fishes as well as some sharks, muscles that originate from the branchial muscle plate and extend medially in the ventral gill arches do exist: the medial extension of the interbranchiales in most batoid fishes and some sharks and the "Y" muscle in the pelagic stingrays Myliobatos and Rhinoptera. The latter is another example of the medial extension of the "internus." Whether the interbranchiales and "Y" muscle are homologous within elasmobranchs and whether homologous with the obliques ventrales and/or transversi ventrales of osteichthyan fishes await further research. Four hypobranchial muscles are recognized in batoid fishes: the coracomandibularis, coracohyoideus, coracoarcualis, and coracohyomandibularis. The coracohyoideus is discrete from the coracoarcualis; its complete structural separation from the latter occurs in several groups of batoid fishes.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1507239 TI - Middle-ear development: II. Morphometric changes in the conducting apparatus of the chick. AB - The ontogeny of various middle-ear structures was examined in 11 groups of chicks between 10 days embryonic and adult. Measurements of the tympanic membrane surface area and height, columella length, and that of the columella footplate, annular ligament, and oval window area were obtained using video micrographs and computer digitization techniques. The oval window matures first at 53 days post hatching, whereas the columella achieves adult size at 74 days. The tympanic membrane surface area is the last middle-ear variable studied to reach adult size (79 days post-hatch). The columella increases its length from 0.63 mm (10 days embryonic) to 2.73 mm in the adult. The tympanic membrane area expands by 280% whereas the columellar footplate area increases by 11x. As a result, the pressure amplification of the middle ear due to the tympanic membrane/columellar footplate area ratio improves by over 400%. These data further contribute to our understanding of the functional development of the middle ear. PMID- 1507240 TI - Four forearm flexor muscles of the horse, Equus caballus: anatomy and histochemistry. AB - Two of the forearm flexors of the horse, the superficial and deep digital flexor muscles, are critical to support the digital and fetlock joints, exhibit differing insertions, and are passively supported by the proximal and distal check ligaments, respectively. These two muscles differ in histochemical composition and architecture. The differences are correlated with the different stress levels transmitted through their tendons, and the different frequencies of clinical breakdown that have been reported. Both muscles contain type I and type IIa fibers. A few type IIb fibers occurred in the deep digital flexor. The superficial digital flexor contained approximately 56% type I fibers, extremely short muscle fibers, and extensive connective tissue investment. In contrast, the deep digital flexor had three muscle heads: ulnar, radial, and "long" and "short" regions of the humeral head. The "long" and "short" regions of the humeral head contained 33% and 44% type I fibers, respectively, fiber lengths three to four times as long as those in the superficial digital flexor, and relatively less connective tissue investment. Flexor carpi radialis and flexor carpi ulnaris compared most closely with the humeral head of the deep digital flexor. These data suggest a correlation of the unique architecture of superficial digital flexor with its proposed elastic storage properties during locomotion in horses, and an explanation for the frequent breakdown of the superficial digital flexor in athletic horses. PMID- 1507241 TI - Spermiophagy by the spermathecal epithelium of the salamander Eurycea cirrigera. AB - The spermathecae of Eurycea cirrigera are exocrine glands in the cloaca that secrete a substance that bathes sperm stored in the lumen after mating and prior to oviposition. Many sperm remain in the spermathecae after oviposition, and the spermathecal epithelium becomes spermiophagic. Pseudopodia enclose sperm into endocytic vacuoles. The vacuoles become associated with primary lysosomes in the cytoplasm. Following formation of secondary lysosomes and resulting condensation of the sperm fragments, residual bodies are exocytized into the surrounding connective tissue stroma. By the start of the next breeding cycle, most sperm remaining from the previous mating have been degraded, but some sperm remain in the lumen, and the viability of these sperm is unknown. PMID- 1507242 TI - Basement membrane lectin binding sites are decreased in the esophageal endoderm during the arrival of presumptive muscle mesenchyme in the developing asteroid Pisaster ochraceus. AB - Basement membranes (BMs) of vertebrates and invertebrates have been shown to contain glycoproteins and proteoglycans, which include oligosaccharides and glycosaminoglycans. Lectin binding sites were characterized in the BM of gastrulating embryos of the starfish, Pisaster ochraceus. In early and mid gastrulae, the fluorescein isothiocyanate (FITC)-lectin conjugates of concanavalin A (Con A) and wheat germ agglutinin (WGA) reveal the presence of mannose/glucose and glucosamine/sialic acid residues in the BM of all regions of the embryos. However, in the late gastrula embryo, an apparent reduction of these components is observed over the esophageal BM. Ultrastructural studies using the lectin-gold conjugates Con A, Limax flavus agglutinin (LFA), specific for sialic acid, and Dolichos biflorus agglutinin (DBA), specific for galactosamine, demonstrate that most mannose/glucose and galactosamine-containing residues lie in the lamina densa, whereas most sialic acid residues are located over the lamina lucida. In addition, a statistical analysis of lectin binding in the late gastrula embryo reveals that the amount of labelling with both Con A and LFA is significantly reduced in the esophageal region, suggesting that mannose/glucose and sialic acid residues are reduced in this region. These results confirm the observations of the FITC-lectin studies described above. They also confirm earlier studies that demonstrated a difference in BM morphology of the esophageal region (Crawford, '88). Mesenchyme cells, some of which arise from the forming coeloms (Crawford, '90), and which may represent a distinct population, colonize exclusively on this esophageal BM, where they later differentiate into muscle. Quantitative differences in BM glycoconjugates may act to direct the presumptive muscle cells to the region of the esophagus. PMID- 1507243 TI - Comparative anatomy and phylogeny of the cloacae of salamanders (Amphibia: Caudata). VI. Ambystomatidae and Dicamptodontidae. AB - Histology of the cloacae of Rhyacotriton olympicus and representative species from the genera Ambystoma and Dicamptodon was examined by light microscopy. Females of Ambystoma possess sperm storage glands, the spermathecae, as well as ventral glands and dorsal glands, both of uncertain function. Females of Ambystoma examined from the subgenus Linguaelapsus differ from those in the subgenus Ambystoma by possessing more extensive ventral gland clusters and a shorter cloacal tube. Females of Dicamptodon possess spermathecae and ventral glands, but differ in cloacal conformation from females of Ambystoma and lack the dorsal glands. Females of R. olympicus possess more extensive epidermal lining in the cloaca than that found in females of Ambystoma and Dicamptodon, and the only glands present are spermathecae, which cluster around a tube in the dorsal roof. Males of Ambystoma, Dicamptodon, and R. olympicus possess five types of cloacal glands (dorsal pelvic glands, lateral pelvic glands, anterior ventral glands, posterior ventral glands, and Kingsbury's glands) that function in spermatophore formation, and vent glands that may produce a courtship pheromone. In Ambystoma and Dicamptodon, vent glands secrete along the medial borders of the cloacal orifice. Males of A. opacum and A. talpoideum differ from males of other species examined from the two genera by possessing more extensive vent glands. Males of R. olympicus possess unique vent glands in which tubules secrete onto the surface of vent lobes lateral to the posterior end of the cloacal orifice, and distal ends of the glands pass anteriorly, superficial to the fascia enclosing the other cloacal glands. The results from analysis of cloacal anatomy support other data indicating that Ambystoma and Dicamptodon are sister groups, and that Rhyacotriton olympicus is not closely related to either of the other two genera and merits placement in a separate family. PMID- 1507244 TI - Healthchoice: a managed health-care program for low-income uninsured workers. AB - The period in which we practice medicine is unprecedented in terms of the enormous changes that are taking place within the profession. Perhaps foremost among the changes is the manner in which the practice of medicine is organized. Historically, over the last 30 years we have witnessed the transition of substantial proportions of physicians as solo practitioners to professionals employed in one form or another by institutional management care systems. Further, from all indications, this change is continuing unabatedly. There are now more than 600 health maintenance organizations (HMOs), and their enrollment rates have been steadily increasing. More than 60 million Americans or about 30% of the insured population receive their medical care through HMOs and preferred provider organizations (PPOs). Moreover, it is estimated that in the year 2000, 90% of all Americans will be receiving their medical care from managed care systems. Clearly, the driving force behind these changes is the desire of third party payers and the public at large to control health-care costs. We, of course, share this goal and are committed to working with the public and private sectors to accomplish this aim. Deborah L. Scott, director of the Wayne County Patient Care Management Systems, writes about HealthChoice, a model managed-care program in Detroit, Michigan. Ms Scott's article is being published in lieu of the President's Column. PMID- 1507245 TI - Multicultural diversity in medicine. PMID- 1507246 TI - The changing perspectives of trauma care. The Sinkler Memorial Lecture. AB - Trauma and the management of injuries have changed considerably over the past century. A sound understanding of the factors that generate injuries and sophisticated systems that can be accessed immediately are now in place in most of the United States. The concept of a team approach to the management of multiple system injuries using specialists from all disciplines has resulted in the reduction of morbidity and mortality. Although many of the challenges of managing the trauma patient have been overcome, there are still a number of exciting areas that lend themselves to ongoing research. These changing perspectives allow for many exciting challenges for the trauma team. PMID- 1507247 TI - Radiographic evidence of calcification in pulmonary hamartomas. AB - Eight cases of solitary intrapulmonary hamartomas are presented to show the unusually high frequency of calcification (75%, six of eight cases) in this series. Possible contributory factors were high percentage of chondromatous variant (seven of eight cases), large size of the tumors, and use of computed tomography. PMID- 1507248 TI - Carcinoma of the male breast in Tanzania. AB - This is a retrospective study of male mammary carcinoma in Tanzania based on biopsy material received from 1974 to 1987 at the Tanzania Cancer Registry. In a series of 1104 cases of breast cancer, 76 or 6.5% were male. This compares with approximately 1% in Western literature, and a similar or higher percentage in some other African countries. In Africa, medical facilities are limited, and appropriate surgical treatment, radiotherapy, and chemotherapy are difficult to procure. By the time cases reach the main hospitals, the cancer is often in a very advanced stage. Thus, there is a need to ensure early referral of cases. Further, for disseminated carcinoma, the more frequent use of orchidectomy should be considered. Orchidectomy is a simple and potentially effective procedure that can be undertaken at any hospital. PMID- 1507249 TI - Black males who always use condoms: their attitudes, knowledge about AIDS, and sexual behavior. AB - One hundred six black males completed a questionnaire concerning attitudes and knowledge about the use of condoms and acquired immunodeficiency syndrome (AIDS). Of the 106 males in the study, 27 (26%) reported that they "always" used condoms, 31 (29%) did not use condoms and had low intentions of using them, and 48 (45%) reported high intentions to use condoms. Results indicated that knowledge about AIDS was exceptionally high for black males in all three groups. Black males with low intentions to use condoms reported significantly more negative attitudes about the use of condoms (eg, using condoms is disgusting) and reacted with more intense anger when their partners asked about previous sexual contacts, when a partner refused sex without a condom, or when they perceived condoms as interfering with foreplay and sexual pleasure. A significantly larger percentage of low intenders were treated for gonorrhea, syphilis, herpes, and genital warts than males in the other groups. Drug use did not differentiate the three groups, although marijuana was used more often by males in the low-intender group. Finally, a larger percentage of black males in the low-intender group reported experiences with anal intercourse and sex with a prostitute, but considered themselves at lower risk for AIDS than did their high-intender or steady-user counterparts. PMID- 1507250 TI - Sunlight and age-related eye disease. AB - Within 50 years, if current trends continue, 50 million elderly Americans will suffer visual impairment from macular degeneration or cataract. However, available evidence indicates that this impending crisis of visual health can be minimized by a simple, safe, inexpensive, and practical means of prevention. Cataract and macular degeneration are the ultimate consequences of normal aging, a lifelong process of deterioration. Three major causes of ocular deterioration have been identified: oxygen, heat, and solar radiation. Among these, the radiation hazard is readily accessible to human intervention. The lens is damaged by ultraviolet radiation in sunlight, whereas the retina can be harmed by high energy visible radiation (the "violet and blue"). Use of sunglasses that block all ultraviolet radiation and severely attenuate high-energy visible radiation will slow the pace of ocular deterioration and delay the onset of age-related disease, thereby reducing its prevalence. A 20-year delay would practically eliminate these diseases as significant causes of visual impairment in the United States. PMID- 1507252 TI - Massive upper gastrointestinal bleeding in a patient with a duodenal diverticulum: a case report and review of the literature. AB - Diverticula of the duodenum occur in approximately 2% to 5% of individuals who have had upper gastrointestinal (GI) series; the majority of these patients are asymptomatic. These diverticula occasionally result in the obstruction of the biliary and pancreatic ducts, which leads to jaundice and pancreatitis. Other complications such as hemorrhage, perforation, sepsis, and death can occur. This article reports a case of upper GI bleeding in a patient who was found to have duodenal diverticula by upper GI series and endoscopy. Diverticulectomy was performed, and microscopic examination of the specimen showed dilated blood vessel suggestive of angiodysplasia. PMID- 1507251 TI - Improving access to a primary care medical clinic. AB - Patients presenting to an episodic care walk-in clinic often warrant prompt but not necessarily emergency attention. Legitimate reasons often prohibit these patients from attending regularly scheduled daytime weekday clinics. Most patients interviewed thought that having a single primary care provider was important to ensure continuity of care. Access to primary care can be improved by scheduling clinics and ancillary services on nontraditional times and days. Enhanced communication can help patients differentiate routine from urgent from emergency conditions. Printed and audiovisual materials can be used to increase awareness of the benefits of comprehensive care. PMID- 1507253 TI - Uterine leiomyosarcoma with intracerebral metastasis: a case report. AB - A case of a 36-year-old woman with a past history of uterine leiomyosarcoma and an intracerebral metastasis is reported. The patient presented with a 24-hour history of severe headache with coma, and the CT findings were consistent with a metastatic lesion. Pathological examination of the operative specimen showed features of a leiomyosarcoma. Uterine leiomyosarcoma is an uncommon tumor and metastasis to the brain is rare. PMID- 1507254 TI - Primary health care. PMID- 1507255 TI - Animal rights issues and African-American health-care providers. PMID- 1507256 TI - The prognostic significance of race and survival from laryngeal carcinoma. AB - Surveillance, Epidemiology, and End Results (SEER) program data suggest that blacks with laryngeal carcinoma have a significantly lower 5-year survival rate than whites. Most of this difference persists despite adjustment for "crude stage." To evaluate possible factors contributing to this residual survival deficit, 190 white and 23 black patients treated at the Martinez Veterans Administration Hospital between 1968 and 1988 were studied. The independent impact of race on survival rate was analyzed with respect to various prognostic factors including treatment delay, elapsed time (diagnosis to treatment), age, stage, cancer subsites, and type of therapy. No independent prognostic significance could be attributed to race. The differences noted in SEER data probably reflect a tendency for the use of crude stage to underestimate the impact of prognostic groups within the categories of "local" and "regional" disease, the independent prognostic significance of subsites (glottic versus supraglottic), and the variable distribution of these subsites in different populations. This study suggests that when stage, subsite, and quality of care are adequately considered, survival from laryngeal cancer in blacks is comparable to that of whites. PMID- 1507257 TI - Review of prostatic surgical procedures at a predominantly black hospital: a 22 year study. AB - This article reports the results of a pathoepidemiological study of a cohort of black men who had prostatic surgery at Howard University Hospital between 1968 and 1989. The median age of patients at diagnosis of prostate cancer increased by 8 years during the study period, indicating either a delay in seeking medical care or a true delay in onset of the disease. The trends of prevalence of biopsies with cancer in various age groups suggested a sharp rise in the incidence of prostate cancer after the age of 70. The significant increase in popularity of needle biopsy during the period 1982 to 1989 after a 7-year plateau is an indication of increased perceived value of this procedure with experience and technical improvement. The prevalence of biopsies with cancer in all successive time periods of the study showed a bimodal distribution with an early hump in the 50- to 54-year-old age group. This hump is analogous to the break in the rising incidence of breast cancer between the ages of 47 and 52 (Clemmesen hook). This similarity could be explained on the basis of hormonal dependence of the two cancers. PMID- 1507258 TI - The public's attitude toward physicians and the care of AIDS patients in the state of Maryland. AB - A telephone survey of 1477 households in Maryland examined the public's attitudes toward physicians and the treatment of AIDS patients. The results indicated that most respondents (86%) want to know their physician's human immunodeficiency virus (HIV) status and that 65% would change physicians if that physician had acquired immunodeficiency syndrome (AIDS). Approximately 50% did not know if their doctor treated AIDS patients, but the majority (68%) responded they would not change doctors because they treated AIDS patients. Significant differences were found in respondents' opinions related to age and education. It was also found that the majority of respondents (57%) received their information about AIDS from the mass media and that very few received their information from medical or other health sources. PMID- 1507259 TI - The effects of acute test anxiety on NBME Part I performance. AB - This study examined the associated effects of acute test-taking anxiety on the performance of a class of second-year medical students who took Part I of the National Board of Medical Examiners (NBME) Examination. The study is a follow-up of a previous study that examined the related effects of chronic anxiety on NBME Part I performance. The purpose of this study was to observe whether there was a relationship between acute anxiety and NBME performance and, further, if there were distinguishable differences in the effects of acute and chronic test anxiety on NBME performance. The first study indicated a significant relationship between chronic anxiety and NBME performance. The results of the present study indicate a relationship between acute test anxiety and NBME performance, but not to the extent associated with chronic anxiety, thus chronic test anxiety may be a more critical factor affecting test performance on critical examinations such as the NBME. Implications concerning anxiety and test performance are discussed. PMID- 1507260 TI - Cholecystectomy in patients with sickle cell disease: experience at a regional hospital in southeast Georgia. AB - The treatment of patients with sickle cell disease and cholelithiasis is controversial. This retrospective study assesses the outcome of preoperative transfusion and timely cholecystectomy in symptomatic sickle cell disease patients. Fourteen patients who had undergone cholecystectomy were determined to have sickle cell disease. The patients' mean age was 17.9 years. Eleven patients were female. Thirteen patients had complained of abdominal pain. Ultrasound confirmed the diagnosis of cholelithiasis in 12 of 13 patients tested. Hemoglobin before treatment averaged 7.7 g/dL. Transfusion or exchange transfusion was given to 12 patients, raising the average hemoglobin to 10.3 g/dL. Postoperative morbidity was 14%: one patient had a urinary tract infection and another a left lower-lobe pneumonia. No sickle cell crises or deaths occurred. Postoperative hospital stay averaged 4.4 days. With judicious use of preoperative transfusion, early cholecystectomy for symptomatic gallstones was well tolerated by sickle cell disease patients and is advisable to avoid the morbid sequelae of acute cholecystitis and peroperative sickle cell crisis. PMID- 1507262 TI - Hyperparathyroidism in black patients: an update. AB - Cervical exploration with removal of the pathologic gland or glands is effective treatment for parathyroid adenomas and hyperplasia. This article reports the results of a retrospective study of 41 patients who underwent elective cervical exploration for primary hyperparathyroidism at Howard University Hospital between 1974 and 1989. Preoperative localization studies for primary neck exploration consisted of an ultrasound of the neck. Removing the diseased gland/glands resulted in the resolution of the patients' symptoms and the return of calcium levels to normal. Complications included transient hypocalcemia, a wound hematoma, and a postoperative death. PMID- 1507261 TI - Interaction of nutrition and infection: effect of copper deficiency on resistance to Trypanosoma lewisi. AB - The copper-deficient rat-trypanosome system was used to study copper deficiency in Sprague Dawley rats infected with Trypanosoma lewisi. Throughout the observational period, animals on the deficient diet had lower plasma and liver copper concentrations compared with complete and pair-fed animals. In all dietary groups, the food intake and body weight changes of rats inoculated with T lewisi showed significant increases over the noninoculated controls. The rate of these indices were significantly less in the copper-deficient animals compared with the animals fed complete diets. Copper-deficient and pair-fed control rats showed greater numbers of parasites than controls throughout the infection. The duration of the trypanosomal infection was longer in copper-deficient rats compared with other groups. In all of the dietary groups, severe depression in the primary and secondary antibody responses (IgM and IgG) to in vivo immunization with sheep erythrocytes was observed in infected animals over noninfected controls. The results of the present study indicate that during copper deficiency, there are significant changes in food consumption and body weight and enhanced susceptibility to infection as measured by an increased parasitemia and depression in the antibody responses. PMID- 1507263 TI - A chronicle of racism: the effects of the white medical community on black health. AB - At no time in history has the health of black Americans equaled that of white Americans. This distinction is particularly evident in the South, where blacks have been subjected to governmental policies promoting discrimination and segregation. The explanations offered for this difference in health status are numerous. The argument presented in this article is that the health status of blacks in the United States has been greatly affected by the attitudes and perceptions of white physicians. From the days of slavery to 1992, the policies and practices of the white medical community have had an enormous impact on the health of blacks. Black physicians have played a large role in changing the delivery of health-care services to the black population. Their fight was a microcosm of the Civil Rights activities taking place in the world around them. This article describes the history of medical care as it relates to black patients and physicians. The progress that has been made over the past century is analyzed, and the need for continued education and persistence is emphasized. Legalized segregation may have been outlawed in the 1960s, but the nation's vital statistics indicate that equality has yet to be achieved. PMID- 1507264 TI - Retrograde extrapolation of blood alcohol data: an applied approach. AB - Retrograde extrapolation is a mathematical process, based on sound scientific principles, that is used routinely in pharmacology, toxicology, and clinical medicine. This process may be applied to the situation of ethyl alcohol consumption with reliability when reasonable assumptions are made concerning absorption rates, elimination rates, and patterns of alcohol consumption, including drinking duration and volume consumed. By utilizing an established range of values for the elimination rate of alcohol of 0.015-0.020 g/dl/h, a relatively narrow range of extrapolated blood alcohol concentrations (BACs) can be determined in situations where the time frame in question is after peak alcohol absorption into the blood. A wider range of elimination rates of 0.01 0.03 g/dl/h may be applied and will satisfy the possibility of nonlinear kinetics within an individual; however, this wider range will have little practical effect on the predicted BACs. When the time point in question is prior to peak absorption, a wider range of predicted BAC values will result. The extent of this range will be influenced by the amount of information available concerning the temporal pattern of alcohol consumption. Reported drinking volumes are notoriously inaccurate and, in fact, are of little practical use. Given the parameters of body weight and time duration between initiation of drinking and determination of the BAC, the number of "drinks" consumed may be reliability calculated. Retrograde extrapolation is applicable in the forensic setting with scientific reliability when reasonable and justifiable assumptions are utilized. PMID- 1507265 TI - Calorimetry: a new quantitative in vitro method in cell toxicology. A dose/effect study of alveolar macrophages exposed to particles. AB - A short-term toxicological test has been developed using a calorimetric method. The metabolic activity, observed as the heat exchange rate, was monitored from alveolar rabbit macrophages in monolayers exposed to different metal and non metal particles. Calorimetric activity indices and viability indices were introduced, from which toxic effects could be assessed. Manganese dioxide particles were found to be cytotoxic. In contrast, titanium dioxide particles seemed to be harmless. The results were in accordance with the cell survival found by use of a fluorescein ester staining method and measured by an image analyzer. Toxic effects from quartz in the form of increased metabolic activity of exposed cells could be detected by the calorimeter in contradiction to the use of the image analyzer. This latter result supports the hypothesis that silica particles cause chronic modification of the macrophage function and that this change in the alveolar macrophage function may be the first of a series of processes leading to pulmonary fibrosis. PMID- 1507266 TI - Steroid synthesis in ovarian homogenates from hypophysectomized adult female mice treated with diethylstilbestrol in neonatal life. AB - Eight-week-old female NMRI-mice treated with 5 micrograms diethylstilbestrol (DES) or vehicle (olive oil) from d 1 to 5 after birth were hypophysectomized or sham operated. Thirty days after the operation, homogenates were prepared from the ovaries and incubated at 37 degrees C in the presence of [3H]pregnenolone for 1 h. In parallel experiments ovaries were taken for histology. In control ovaries regressing corpora lutea were still present 4 wk after hypophysectomy (Hx). Ovaries from DES females had no corpora lutea, but showed degeneration of the pre Hx hypertrophic interstitial tissue. Steroids synthesized during the incubation were extracted and separated in a two-dimensional thin-layer chromatography system. After Hx, the amount of extractable [3H]testosterone, [3H]progesterone, and [3H]androstenedione recovered from homogenates of vehicle-treated females increased, but the amount of recovered [3H]-17 alpha-hydroxyprogesterone was not significantly altered. In contrast, in DES-treated females Hx significantly decreased levels of [3H]androstenedione and [3H]-17 alpha-hydroxyprogesterone, but did not affect [3H]progesterone or [3H]testosterone. The persistent difference in steroid synthetic activity after Hx could be linked to the difference in morphology between different ovarian tissue compartments of control and DES-treated females. PMID- 1507267 TI - Exposure assessment for heavy metal ingestion from a sport fish in Puerto Rico: estimating risk for local fishermen. AB - Sport or subsistence fishermen sometimes underestimate the risks from eating local fish and distrust authorities regarding potential hazards from fish. We report on lead, cadmium, selenium, and mercury levels in snook, locally called robalo (Centropomus spp.), consumed by local fishermen in Puerto Rico, who ate up to 23 fish/wk. Median levels (in ppb, dry weight) for muscle, adipose, and liver ranged from 683 to 780 for lead, 37 to 600 for cadmium, 50 to 146 for mercury, and 361 to 3986 for selenium. Lead levels were similar in all tissues, and selenium and cadmium levels were highest in the liver. Mercury was higher in muscle than in liver. Computing exposure via ingestion for the average fisherman indicated that if one were to consume robalo throughout the year one would be exposed in excess of the EPA Reference Dose (RfD) for mercury. Using a widely accepted maximum consumption of 200 g/d for fishermen yielded hazard indices (daily consumption/RfD) below 1 for all four metals, with a value approaching 1 for mercury in adults, and over 1 for 16-kg children. The possibility that in certain localities and cultures sport or subsistence fishermen may consume fish at levels substantially above 200 g/d should be investigated in performing risk assessments, particularly outside the continental United States. PMID- 1507268 TI - Dermal penetration of 14C-labeled diisopropyl methylphosphonate in swine. AB - Diisopropyl methylphosphonate (DIMP) has been identified as a groundwater contaminant on or near sites of former chemical warfare production facilities. The material is a by-product of GB (or Sarin) manufacture and does not occur naturally in the environment. The present study measured the dermal absorption of 14C-labeled DIMP in swine to establish the basis for estimating health risk from this portal of entry. Yorkshire cross swine were treated by sc injection of labeled DIMP to measure the efficiency of bioelimination. Additional pigs each received a single percutaneous (pc) exposure of 400, 40, or 4 micrograms/cm2 of labeled DIMP. Absorption through 7 d was measured by the appearance of 14C label in the urine and feces. Tissue specimens, collected at necropsy, were assessed for residual radioactivity. The results showed that between 3 and 7% of cutaneous DIMP was absorbed through 7 d. Urinary elimination accounted for about 95% of the absorbed dose in the first 24 h. No significant tissue deposition was observed. Pigs treated by the sc route excreted nearly 100% of the injected material demonstrating an extremely efficient metabolic process. It was concluded that humans may be expected to absorb less than 10% of an unoccluded single dermal exposure to DIMP. Absorbed dose would likely be metabolized to isopropyl methylphosphonic acid and excreted primarily in the urine within 24 h. Significant evaporation of the material from the open skin surface would be expected to occur. PMID- 1507269 TI - Fetal detriment used as an index of effects of diethylene glycol on Syrian hamster fetuses. AB - The effect of diethylene glycol (digol, diEG; specific gravity = 1.12) on the embryo was studied in the pregnant Syrian hamster at dosages from 2 1/4 to 4 ml/kg (2.52-4.48 g/kg). The hamsters were dosed by (single) intraperitoneal injection because previous experiments had indicated that oral dosing in the drinking water (and therefore possibly gavage dosing also) causes the hamsters to drink less. The digol was diluted with distilled water and injected on d 8 of pregnancy. Distilled water was used for the controls. At all dosages, fetuses from treated animals examined at autopsy on d 15 were found to be lighter than those from control animals. Abnormalities were seen at all dosages, mainly neural tube defects (exencephaly, cranial bleb, and myelomeningocele). No neural-tube defects were observed in control animals. A dosage-related deficit in the number of live, externally nonmalformed fetuses was observed and was matched by a dosage related increase in the number of live externally abnormal fetuses. Few dead full term fetuses were found, but there was a dosage-related increase in the "late" resorption rate. A new summarizing measure, the fetal detriment (FD), the deficit from control expectations of live, nonmalformed litter mass per live litter, was found to be proportional to the square of the dose-rate D, the regression through the origin in this study being FD = (0.934 +/- 0.329)D2. The 50% attrition dosage, the AD50, was 2.90 ml/kg (3.25 g/kg) in the hamster, with 95% confidence interval 2.21-5.41 ml/kg (2.48-6.06 g/kg). Diethylene glycol in high dosage produces damage to the fetuses of pregnant Syrian hamsters. It is not known whether this is an indirect result of the maternal toxicity, which was observed even at the lowest dosage used, or is the effect of digol or of its metabolites on the conceptus. PMID- 1507270 TI - Acute and "long-term" genotoxic effects of CdCl2 on testes of mice. AB - The effects of Cd administered ip in a single carcinogenic dose (1 mg Cd/kg body weight) into male CFLP mice were investigated on the histological and cytogenetic status of the testes of the animals on d 3 and 6 mo after the Cd injection. There were some characteristic histological changes in the testes of the mice on d 3 after Cd treatment: the presence of interstitial hemorrhages, the death of Leydig cells, sterile necroses of tubular elements, and numerous atypical mitoses of the spermatocytes. A significant increase compared with the control was found only in the number of numerical chromosome aberrations in the Cd-treated group. Six months later, a significant difference compared with the control was found only in the relative weight of the testes in the treated group. There were soon no detectable effects of Cd on the histological picture of the testes and on the spermatocytes. PMID- 1507271 TI - Toxicity and toxicokinetics of carbaryl in chickens and rats: a comparative study. AB - Carbaryl, a carbamate insecticide, exerts its toxic effect in animals by inhibiting the activity of neural acetylcholinesterase. Differences in sensitivity of this enzyme to inhibition were studied after intraperitoneal administration to chickens and rats. A dose of 900 mg/kg to chickens and 70 mg/kg to rats caused equivalent inhibition of brain cholinesterase activities (57% +/- 6 and 47% +/- 4, respectively) 60 min after administration, which was the time of maximal cholinergic signs. Signs of toxicity (salivation, respiratory distress, muscle tremors and weakness) were more pronounced in rats than in chickens when brain acetylcholinesterase was inhibited to the same extent in both species. Carboxylesterase activities in brain, liver, and plasma were also inhibited 60 min after administration of carbaryl to chickens and rats. Activities of enzymes associated with hepatic microsomes were unaffected. Specific activities of brain esterases, including acetylcholinesterase, carboxylesterase and neurotoxic esterase, were higher in untreated chickens than in untreated rats. Specific activities of liver esterases (carboxylesterase, A-esterase) were, however, 4- and 10-fold lower in untreated chickens than in untreated rats. Total clearance of carbaryl in the chicken, determined after intravenous administration of 5 mg/kg, was 0.26 +/- 0.02 l/kg/min. This value is 5.7 times higher than that reported for the rat, indicating that the relatively lower activities of esterases in the liver of chickens did not affect the clearance of this chemical in the avian species. PMID- 1507272 TI - Thrombocytopenia and leukocytosis induced by single intravenous injections of cadmium-saturated metallothioneins-I and -II in rats. AB - To comparably investigate hemotoxic potentials of CdCl2, cadmium-saturated metallothioneins-I (Cd-MT-I) and -II (Cd-MT-II), rats received single intravenous injections of one of those dissolved in saline with equivalent concentrations of Cd (0, 0.1, 0.3 and 1.0 mg Cd/kg body weight), and blood for hematological examinations was sampled at 1 and 5 days (Days 1 and 5) after the administrations. The counts of white blood cells showed dose-dependent increments in the 0.3 and 1.0 mg Cd/kg groups in Cd-MT-I and Cd-MT-II at Day 1, and returned to the normal levels at Day 5. The counts of platelets showed dose-dependent decrements in the three-doses groups of Cd-MT-I and Cd-MT-II at Day 1, and did a returning- and further increasing tendency at Day 5. The counts of red blood cells, values of hematocrit, hemoglobin, mean corpuscular volume, mean corpuscular hemoglobin and mean corpuscular hemoglobin concentration, showed only slight and sporadic changes at Days 1 and 5. As to that thrombocytopenia and leukocytosis were dose-dependently brought by Cd-MTs and not by CdCl2, and as to that CdCl2 and Cd-MTs hardly affected erythrocytes regarding their counts, sizes, hemoglobin contents etc., etiological mechanism (s) remains to be explored. However, our findings should be clinically emphasized in relation to Itai-Itai disease and Cd-intoxication. PMID- 1507273 TI - Disturbance or relatively important actions of antihypertensives, antifungal agent and opiate antagonist to the testicular steroidogenesis in rat. AB - Some of antihypertensives, opiate antagonist and antifungal agent can interfere with sexual function in both men and women. Drug-related effects on sexual function may be difficult to distinguish from the direct action of gonadal function. Clinically well known those agents to have sexual dysfunction were selected and examined the direct effect on rat's testicular steroidogenesis in vitro. Donryu rats were decapitated at 11 weeks old and isolated testes were decapsulated and preincubated with Krebs-Ringer-phosphate buffer (KRP) added with 1 micrograms/flask of LH for 60 min at 37 degrees C. Then, incubation was made with prazosin (1 micrograms), clonidine (5 micrograms), verapamil (10 micrograms), naloxone (5 micrograms) and ketoconazole (150 micrograms), 37 degrees C for 180 min in fresh KRP-buffer, respectively. Steroids were analysed with RIA, and microfluorometry after purification with quantitative thin layer chromatography. Prazosin had a tendency to produce dihydrotestosterone (DHT) indicating a facilitation of 5 alpha-reductase, and clonidine showed a significant production of estradiol (E2) with a slight production of DHT indicating a significant facilitation of aromatase. Verapamil had a action to produce significantly E2 with a slight production of DHT, and naloxone showed a significant production of both DHT and E2. Thus, these two agents showed facilitation of both 5 alpha-reductase and aromatase. Ketoconazole had a significant production of both delta 4-androstenedione (delta 4-A) and E2 while it had a significant inhibition of DHT-production, thus this had a significant production of both aromatase and C17,20-lyase while had a significant inhibitory action of 5 alpha-reductase. These findings indicates that comparatively large doses of central-nervous system depressants are one of the factors that interfere with sexual function, but it is not necessary to have direct action to testicular function, however present study revealed that some of them can cause gonadal damage and consequently progressive loss of libido. PMID- 1507275 TI - Behavioral evaluation of psycho-pharmacological and psychotoxic actions of methylxanthines by ambulatory activity and discrete avoidance in mice. AB - The behavioral effects of methylxanthines, caffeine, theophylline and theobromine, were compared by means of ambulatory activity and discrete lever press avoidance response in mice. The single oral administration of 10-100 mg/kg of caffeine, 30-300 mg/kg of theophylline, and 10 mg/kg of theobromine significantly increased the mouse's ambulatory activity. However, 1000 mg/kg of theobromine decreased the activity. The ambulation-increasing effect of methamphetamine (2 mg/kg s.c.) was enhanced by coadministration with caffeine (3 100 mg/kg), theophylline (10-300 mg/kg), and theobromine (10-100 mg/kg). On the other hand, comparatively higher doses of caffeine (up to 30 mg/kg) slightly but significantly decreased the avoidance rate without eliciting any significant change in the response rate. Theobromine significantly decreased the response rate at higher than 300 mg/kg, and the avoidance rate at higher than 100 mg/kg. Furthermore, 1000 mg/kg of theobromine was much toxic for mice, i.e., half mice died within a few hr after the end of the 1-hr avoidance session. Theophylline did not produce any significant change in the avoidance response at the dose range of 3-300 mg/kg. These results may indicate the relative order of the centrally stimulant and/or behavioral toxic actions of methylxanthines in human. PMID- 1507274 TI - Chronic toxicity of microencapsulated bromodichloromethane administered in the diet to Wistar rats. AB - A chronic feeding study was carried out in Wistar rats using microencapsulated bromodichloromethane. The test substance was administered in the diet at doses of 0, 0.014, 0.055 and 0.22% for 24 months. Rats were sacrificed after 6, 12, 18 and 24 months of continuous dosing. The results showed a suppression of body weight gain in the 0.22% group for both males and females. Dose related changes were clearly observed in the liver with histopathological findings including fatty degeneration in the 0.014% or higher dose male groups, and fatty degeneration and granuloma in the 0.055 and 0.22% group females, as well as bile duct proliferation and cholangiofibrosis in the 0.22% group for both males and females. No significant differences in incidences or numbers of neoplastic changes were seen between control and any of the treatment groups. There were no dose-related non-neoplastic lesions in the kidneys of either sex. Lowest-observed adverse-effect-level was determined to be 6.1 mg/kg/day under the present experimental conditions. PMID- 1507276 TI - The baseball bat: a popular mechanism of urban injury. AB - From January 1989 through December 1990, 74 patients were admitted to our urban level I trauma center with injuries inflicted by baseball bats. We investigated the demographics and dynamics of injury in these patients by retrospective analysis of the patient's medical record and Trauma Registry data. The average victim was 30 years old. Ninety-two percent of the patients were male, and approximately 89% tested positive for substance abuse. Injury to both the head and body occurred in 80% of our patients, isolated head injury occurred in 42%. Twenty percent suffered injury to the body only. On admission, 7% went directly to the operating suite, 16% were admitted to the trauma ICU, one patient was admitted to the pediatric ICU, and the remainder were admitted to the floor shock/trauma unit. These patients had a length of stay (LOS) that was not significantly different than the LOS for patients with penetrating trauma or the general trauma population. The mean Trauma Score was 13.8 (range, 6-16), and the average Injury Severity Score was 10.5 (range, 1-34). The mortality in our study was 3%. Four percent of the patients were left with some degree of permanent disability. Intentionally inflicted injury is most commonly seen in the thorax and abdomen. In contrast, head injury was evident in 80% of our patients with baseball bat injury. This represents a departure from classic patterns of violent injury. PMID- 1507277 TI - Induced immunoglobulin secretion by T-cell-replacing products from blunt trauma patients. AB - The capacity to induce immunoglobulin (Ig) secretion by soluble T-cell-replacing (TCR) factors derived from alloantigen-stimulated T lymphocytes of blunt trauma patients (n = 15, mean ISS = 24) was examined in Staphylococcus aureus (SAC) activated normal B-cell cultures. The majority of the patients studied demonstrated a profound suppression of the T-cell-dependent, pokeweed-mitogen induced Ig production. However, the activity to induce Ig secretion associated with TCRs from the same patients was not reduced compared with that of TCRs from normal subjects. IgM synthesis was normal and IgG secretion induced by TCRs was within the control range (in 6 of 15 patients) or significantly higher (p less than 0.05) than that in the remaining patients. Both patient-derived and control TCRs failed to induce Ig synthesis in cultures of resting B cells and had comparable mitogenic effects on normal SAC-activated and phytohemagglutinin A activated B and T lymphocytes, respectively. Thus, the intrinsic ability of T lymphocytes to produce B-cell helper factors appears to be unaffected following blunt trauma. Suppression of the T-cell-regulated Ig secretion in traumatized patients may therefore reflect an altered B lymphocyte response to such factors. PMID- 1507278 TI - Osteosynthesis of irreducible fractures of the clavicle with 2.7-MM ASIF plates. AB - Thirty-six patients with Allman group-2 fractures of the clavicle were treated by ORIF with 2.7-mm ASIF dynamic compression plates. The indications for surgery were an open fracture in one patient, ipsilateral fractures of the arm or the ribs in five patients, bilateral clavicular fractures in one patient, and an inability to reduce the fracture in all other patients. There were no instances of deep infection. One patient suffered a refracture after plate removal; three patients developed pseudarthrosis because plates that were too short were used. The total failure rate was 12%. It is concluded that the 2.7-mm DCP is the method of choice for internal fixation of midshaft clavicular fractures and that a minimum of three screws should be placed in each fragment. PMID- 1507279 TI - The hands of friendship--consumer or contributor: 1991 presidential address, Trauma Association of Canada/l'Association canadienne de traumatologie. PMID- 1507280 TI - Traumatic injury to the diaphragm: timely diagnosis and treatment. AB - Traumatic injury to the diaphragm is a relatively uncommon injury with potential for considerable morbidity if the diagnosis is delayed or missed. This review of cases of traumatic diaphragmatic injury was undertaken in order to emphasize methods and timing of diagnosis and treatment. From 1986 through 1990, 43 cases of traumatic diaphragmatic injury were admitted to the trauma unit at Sunnybrook Health Sciences Centre, for an incidence of 2% of all new multiple trauma admissions. All patients were evaluated and treated by a dedicated trauma team. The left hemidiaphragm was injured in 32 patients, the right hemidiaphragm was injured in eight cases, and the injury was bilateral in three patients. Thirty four patients had blunt trauma. The mean Injury Severity Score for all patients was 32. The diagnosis of diaphragmatic injury was made radiologically in 21 cases and at surgery in 22 cases. The diagnosis in all cases with penetrating trauma was made at the time of surgery. The interval between injury and definitive surgery was less than 12 hours in 39 of 43 patients. The diagnosis of diaphragmatic injury was delayed by more than 12 hours in only one patient. The other three patients were diagnosed soon after injury but their definitive surgery was delayed for other reasons. Surgical repair of the diaphragm was performed via laparotomy in 40 of 43 cases. Only one patient was repaired in a delayed fashion by thoracotomy for thoracic complications. A clear contrast can be drawn between blunt injuries and penetrating trauma.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1507281 TI - The Integrated Trauma Program: a model for cooperative trauma triage. AB - The Integrated Trauma Program (ITP) is the cooperative trauma triage service of the University of Toronto trauma and burn hospitals and the Ontario Ministry of Health. It provides physicians in referring hospitals direct access to a trauma team leader (TTL) in one of several trauma centers through a single phone number. Three adult trauma centers, one pediatric trauma center, and one burn center, all affiliated with the University of Toronto, participate in this program. This article describes the system during the first two years of operation. From July 1989 to June 1991, 1530 requests for patient transfers from a total of 97 hospitals were processed. Of these transfer requests, 77% were accepted by the TTL to a trauma service as multiple trauma cases, 16% were accepted directly to a surgical service without involving the trauma team, 4% were refused by the TTL as inappropriate referrals, and 3% of requests were cancelled by the referring physician. The transfer requests are distributed to a specific trauma center by request of the referring physician (10%), according to a rotation (70%), or as selected by the ITP (20%) when the scheduled hospital is not readily available. Closure of all adult trauma centers occurred on 43 occasions. During these closures, 48 patients bypassed the Toronto trauma centers and were transferred to other cities. The ITP office also keeps an ongoing data base of patients transferred. The mechanism of injury in the majority of cases is vehicular crashes. The mean Injury Severity Score is 24 for adults and 17 for children.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1507282 TI - Standardized mortality ratio analysis on a sample of severely injured patients from a large Canadian city without regionalized trauma care. AB - Flora's Z statistic and standardized mortality ratios (SMRs) as indicators of excess mortality were calculated for a sample of 355 patients with major trauma. A statistically significant overall excess mortality was observed in this sample (Z = 6.77, SMR = 1.81, p less than 0.05). Advanced life support provided by physicians at the scene (MD-ALS) was not associated with reduced excess mortality. A significant trend toward lower excess mortality was associated with a higher level of trauma care at the receiving hospital (p less than 0.05). Total prehospital time over 60 minutes was associated with a significant increase in excess mortality (p less than 0.001). These results support regionalization of trauma care and failed to show any benefit associated with MD-ALS. PMID- 1507283 TI - Is a full team required for emergency management of pediatric trauma? AB - Pediatric trauma centers often do not meet the guidelines requiring a trauma team as recommended by the American Academy of Pediatrics (AAP). We reviewed our experience with a team consisting of a pediatric emergency physician, resident, nurse, and respiratory therapist. The surgical and pediatric critical care residents and staff were available within 5 minutes. We conducted a retrospective chart review of 146 patients (aged 8.1 +/- 4.8 years) between 1987 and 1989, with Injury Severity Scores (ISS) greater than or equal to 16 or admitted to the pediatric critical care unit. The time of presentation, surgical services consulted, and the nature of the injury were obtained from chart review. The Pediatric Trauma Score (PTS), the Revised Trauma Score (RTS), the Injury Severity Score (ISS), Glasgow Coma Scale (GCS) score, and Pediatric Risk of Mortality (PRISM) were used to determine the severity of insult and physiologic derangement on admission. The Modified Injury Severity Score (MISS) was determined and the Delta score for Disability Assessment was assigned at discharge. The Delta score was also determined at 3-month intervals up to one year. The probability of survival (Ps) was calculated, using the ISS and RTS. The Z statistic for this group of patients was then determined, using the Major Trauma Outcome Study (MTOS) methodology. The percentages of patients who were normal, disabled, and dead were 61%, 31.5%, and 7.5%, respectively, at 6 months follow-up. Eleven deaths were expected based on PRISM and TRISS analysis. Our mortality and morbidity figures were comparable with those of centers with teams based on AAP guidelines.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1507284 TI - Injury severity score, head injury, and patient wait days: contributions to extended trauma patient length of stay. AB - The ability of level I trauma units to operate efficiently may be hampered by the presence of a number of patients with an excessive length of stay (LOS). In an attempt to determine causes for and suggest potential solutions to the long-term occupation of beds in an acute care trauma facility, the cases of patients with extended LOSs in a level I trauma unit were examined. Study patients were survivors admitted between January 1, 1986, and December 31, 1989. Patients with a LOS greater than one standard deviation above the mean (n = 221) were assigned to the Long LOS group, and the remaining 1250 patients to the Short LOS group. Long and Short LOS patient groups were compared on a number of variables including injury Severity Score, number of body systems injured, surgical procedures required, blood products used, AIS scores per body region, and patient wait days. Both an increased severity of injury and a lack of available chronic and rehabilitation beds for the head-injured patients contributed to excessive patient LOS in this acute care setting. Additional rehabilitation and chronic care beds are required to free acute care beds for the efficient operation of a level I trauma unit. PMID- 1507285 TI - The effects of ischemia and ischemia-reperfusion on bacterial translocation, lipid peroxidation, and gut histology: studies on hemorrhagic shock in pigs. AB - The bacterial translocation hypothesis was tested in two studies (acute and subacute) in a porcine model of hemorrhagic shock. Male pigs (30-40 kg each) under general anesthesia had their femoral vein, femoral artery, and portal vein catheterized. After stabilization (1 hour) they were bled (40% of blood volume) over 30 minutes, then maintained in the hypotensive state (MAP = 30-40 mm Hg) for 2 hours, following which, according to randomization, they entered the control group or were resuscitated with whole blood (WB group) or with lactated Ringer's solution (LR group). In the acute study, the mesenteric efferent lymphatic was also cannulated, the control group was not resuscitated, and the animals remained under general anesthesia to the end of the experiment (8.5 hours), when gut tissue was obtained for histologic study and measurement of lipid peroxidation. In the subacute study, the control group was not bled, the animals were awakened at 6.5 hours, and the portal vein catheter remained in situ until 48 hours. In both studies, samples of portal blood were obtained for culture at regular intervals and on completion, samples from mesenteric lymph nodes (MLNs) for culture were taken in the acute study, and in the subacute study samples from MLNs, spleen, and liver were obtained. In the acute study significant bacterial translocation to the MLNs and portal blood did not occur among the controls (n = 3), the LR group (n = 5), and the WB group (n = 6). Significant evidence of lipid peroxidation was found in both the LR and WB groups. Histologic assessment showed no difference among the groups.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1507286 TI - Body habitus as a predictor of injury pattern after blunt trauma. AB - The records of obese and nonobese victims of blunt trauma were compared to determine if obese individuals are predisposed to a specific injury pattern. Prospectively collected data on 6368 adults admitted to a level I trauma center over a 4-year period were analyzed. Twelve percent (743 patients) met Body Mass Index (weight/height2) criteria for obesity (greater than or equal to 30 kg/m2). The obese group was older (p less than 0.01) and had lower ISSs (p less than 0.05) and higher GCS scores (p less than 0.01). More obese patients were injured in vehicular crashes (62.7% vs. 54.1% [p less than 0.01]). The obese victims were more likely to have rib fractures, pulmonary contusions, pelvic fractures, and extremity fractures and less likely to have incurred head trauma and liver injuries (p less than 0.05). Obese people injured in vehicular crashes had a similar injury pattern with no difference in seating position, direction of impact, seat belt use, and ejection. PMID- 1507287 TI - The cardiorespiratory effects of increased intra-abdominal pressure in diaphragmatic rupture. AB - The cardiorespiratory effect of gastric herniation in diaphragmatic rupture with and without increased intra-abdominal pressure (produced by inflation of a pneumatic antishock garment [PASG] to an intraperitoneal pressure of 40 mm Hg) was studied in 16 anesthetized spontaneously breathing (80% oxygen) piglets. Four additional animals had similar measurements after PASG inflation but without diaphragmatic rupture. Arterial blood pressure (BP), cardiac output, arterial blood gases, position of the stomach relative to the diaphragm (as measured on fluoroscopy), and mortality were assessed. Gastric herniation without the PASG (group I: 8 animals) produced slight cardiorespiratory deterioration, with PO2 falling from a baseline measurement of 429 +/- 60 mm Hg to 316 +/- 5 mm Hg at 1 hour. Over this period pH decreased from 7.39 +/- 0.05 to 7.30 +/- 0.02 and PCO2 increased from 39 +/- 5 to 46 +/- 2 mm Hg. With PASG inflation (group II: 8 animals) PO2 decreased to a greater extent, from 410 +/- 30 mm Hg at baseline to 48 +/- 10 mm Hg by 1 hour; pH decreased from 7.38 +/- 0.06 to 6.8 +/- 0.2 and PCO2 increased from 39 +/- 4 to 88 +/- 6 mm Hg. Animals without diaphragmatic rupture (group III: 4 animals) showed a smaller decrease in PO2, from 480 +/- 34 mm Hg at baseline to 320 +/- 50 mm Hg by 1 hour after PASG inflation.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1507288 TI - Significance of myocardial contusion following blunt chest trauma. AB - A prospective study was undertaken at a regional trauma unit (RTU) to determine the significance of cardiac complications in patients with blunt chest trauma. Radionuclide angiographic (RNA) imaging was performed as soon as possible after admission and Holter monitors were applied for 72 hours. Routine investigations included serial cardiac enzyme measurements and 12-lead electrocardiograms. Dysrhythmias were classified and ventricular dysrhythmias were stratified by ventricular ectopic score (VES) as ventricular tachycardia (4) or greater than 100 premature ventricular contractions (PVCs)/hour (3). Three hundred twelve patients were entered into the study. Analysis of dysrhythmias revealed 18 patients with a VES of 4 and nine patients with a VES of 3; there were no serious consequences. The most significant dysrhythmia as a marker of outcome was atrial fibrillation (n = 9); five of these patients died, but all of associated noncardiac injuries. A review of abnormal RNAs revealed that all associated mortalities were attributed to noncardiac injuries. A review of postmortem reports and hospital records revealed that no deaths were attributed to cardiac failure or dysrhythmia. Thus the incidence of clinically significant dysrhythmias or other cardiac complications resulting from blunt trauma to the heart may be overestimated. PMID- 1507289 TI - Neurophysiologic diagnosis in uncooperative trauma patients: confounding factors. AB - Median, ulnar, and posterior tibial nerve somatosensory evoked potential (SSEP) studies were performed on a total of 239 comatose or uncooperative trauma patients with head injuries. Twenty-six of those patients were suspected of having an additional spinal cord injury. One patient had more than one suspected spinal cord injury and two patients had a suspected spinal cord injury and a suspected peripheral nerve injury. Eleven of the suspected spinal cord injuries were confirmed and 13 were not confirmed by the SSEP studies. In three patients the SSEP study proved inadequate to add further information on the suspected spinal cord injury. Sixteen patients with suspected spinal cord injuries were able to cooperate with a neurologic examination approximately 6 months after injury and the SSEP findings were clinically verified in all 16 patients. Eleven patients were suspected of having an additional peripheral nerve injury. Four injuries were confirmed and seven not confirmed by the SSEP studies. Eight of those patients were able to cooperate with the follow-up neurologic examination, and the SSEP findings were clinically verified in all eight. Two patients suspected of having an additional spinal cord injury had unsuspected peripheral nerve injuries discovered by the SSEP studies. One patient was cooperative at follow-up and the SSEP findings were clinically verified. In our experience, SSEP studies have been an important diagnostic tool in the study of uncooperative trauma patients. PMID- 1507290 TI - The physical, psychological, and socioeconomic costs of pediatric trauma. AB - This prospective study examined the physical, psychological, and socioeconomic effects of injuries on children and their immediate families. Ninety-two injured children admitted with minor (ISS less than 16) or major (ISS greater than or equal to 16) injuries were compared with a control group of 59 children admitted during the same period with acute appendicitis. The two populations were similar in mean age, sex ratio, parental age and work status, and number of siblings. The parents of the injured children had a lower level of education than those of the controls. Fifty-four percent of the minor injury patients and 71% of the major injury patients had persistent physical limitations at 12 months in contrast to none of the controls. Thirty-eight percent of minor injury patients had pre existing behavioral disturbances compared with 14% of major injury patients and 10% of controls. Behavioral disturbances among major trauma patients showed a sharp rise to 41% at 12 months and tended to persist in cases with continuing physical limitations. The major injury patients and those with significant head injuries exhibited a decrease in academic performance; minor injury patients and those without head injury showed no change. Maternal malaise rose sharply to about 40% in both injury groups in contrast to 7% in the controls and was more common in the presence of persistent physical limitations. Only 73% of families in the major injury group had returned to normal family life compared with 87% of the minor injury group and 100% of controls.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1507291 TI - Trends in hospital care of burns in Canada. AB - A review of burn admission patterns to Canadian hospitals from 1966 to 1991 from Statistics Canada data was prompted by a decrease to 125 burn patients admitted to Vancouver General Hospital in 1990 after a plateau at 180-195 per year for 6 years. The total number of fires from Fire Commissioner's data and data from 20 of the 27 Canadian burn units was analyzed. Canadian burn admissions decreased from 57 per 100,000 in 1966 to 23 per 100,000 in 1989. The admission rate is three times greater for children 0-4 years of age but has decreased parallel with the total. The number of fires decreased from 370 to 270 per 100,000 in the last decade. In 1981, 1986, and 1989 15 Canadian units treated a constant 15% share of hospitalized burns, while nine units reported a constant 7% of burn patients who also required ventilation for associated smoke inhalation injury. These trends forecast a 2%-4% decrease in hospitalized burns per capita per year. PMID- 1507292 TI - Surgical repair of traumatic tricuspid insufficiency: report of three cases. AB - Traumatic tricuspid insufficiency (TTI) is a rare lesion but is classically encountered as a "steering-wheel injury" in nonbelted car divers. This lesion is often not diagnosed because of its subtle clinical manifestations at first and the presence of associated injuries in multiple trauma. The majority of patients reported were treated with valve replacement but, more recently, successful repair of the native valve has made the latter the treatment of choice. Three patients were referred to us with a delayed diagnosis of TTI 2, 4, and 8 years after being involved in motor vehicle crashes (MVCs). Surgery was required and consisted of resuspension of the valvular leaflet with autogenous pericardium and ring annuloplasty. Two-dimensional echocardiography confirmed tricupid valve competence and the patients remained symptom free at a mean follow-up of 25 months. PMID- 1507293 TI - EAST Presidential Address: Reflections on and directions for trauma care. PMID- 1507294 TI - Effect of increased intra-abdominal pressure on hepatic arterial, portal venous, and hepatic microcirculatory blood flow. AB - The effects of increased intra-abdominal pressure (IAP) on hepatic perfusion were studied in five anesthetized pigs. Doppler flow probes were used to measure hepatic artery blood flow (HABF) and portal venous blood flow (PVBF), and laser Doppler flowmetry was used to assess changes in hepatic microvascular blood flow (HMVBF). Hepatic blood flow responses to 10, 20, 30 and 40 mm Hg increases in IAP were assessed while the mean arterial BP (MAP) was maintained at baseline levels with IV crystalloid infusions. Although cardiac output and MAP were normal, HABF and HMVBF fell significantly with 10 mm IAP, and at 20 mm Hg IAP, HABF was 45% of the control value, PVBF was 65% of the control value, and HMVBF was 71% of the control value (p less than 0.05). At 30 and 40 mm Hg, hepatic blood flow was reduced even more. Thus, modest increases in IAP can cause significant impairment of hepatic perfusion despite a normal BP and cardiac output. PMID- 1507295 TI - High-level positive end-expiratory pressure management in trauma-associated adult respiratory distress syndrome. AB - This study evaluated the effect of high-level positive end-expiratory pressure (PEEP) on mortality, barotrauma, intrapulmonary shunt (Qsp/Qt), and oxygen delivery (DO2) in posttraumatic adult respiratory distress syndrome (ARDS). All hypoxemic trauma patients admitted to the surgical intensive care unit (SICU) in 1989-1990 who received PEEP greater than 15 cm H2O were included. The PEEP was titrated to achieve an intrapulmonary shunt (Qsp/Qt) of approximately 0.20, and FIO2 was weaned to less than 0.50. Hemodynamic and pulmonary variables at four distinct intervals were recorded. Fifty-nine patients received PEEP greater than 15 cm H2O. Of these, 19 patients died of severe head injury or uncontrollable hemorrhage (16 within 48 hours). Forty (29 male, 11 female) were evaluated in detail. The PEEP levels ranged from 18-50 cm H2O with a mean of 27. PaO2/FIO2 ratios and Qsp/Qt improved as PEEP therapy was titrated. Cardiac index and oxygen delivery were maintained or improved throughout PEEP therapy by transfusion and fluid resuscitation, with a mean maximum positive fluid balance of 21.1 L and an average of 51 units of blood and blood products transfused per patients during their SICU stay. Twenty-nine (73%) had evidence of barotrauma, the majority being pneumothoraces clearly related to the initial trauma. Only three (7.5%) had evidence of barotrauma not related to trauma or line insertion. Eight of 40 patients (20%) died. Mean ISS and RTS for the entire group were 32 and 5.88, respectively. We conclude that titration of PEEP to achieve a Qsp/Qt of approximately 0.20 is an attainable goal. This was accomplished with minimal hemodynamic effects or barotrauma and a low mortality rate. PMID- 1507296 TI - Inter-rater reliability of preventable death judgments. The Preventable Death Study Group. AB - This study examined the inter-rater reliability of preventable death judgments for trauma. A total of 130 deaths were reviewed for potential preventability by multiple panels of nationally chosen experts. Deaths involving a central nervous system (CNS) injury were reviewed by three panels, each consisting of a trauma surgeon, a neurosurgeon, and an emergency physician. Deaths not involving the CNS were reviewed by three panels, each consisting of two trauma surgeons and an emergency physician. Cases for review were sampled from all hospital trauma deaths occurring in Maryland during 1986. Panels were given prehospital and hospital records, medical examiner reports, and autopsy reports, and asked to independently classify deaths as not preventable (NP), possibly preventable (POSS), probably preventable (PROB), or definitely preventable (DEF). Cases in which there was disagreement about preventability were discussed by the panel as a group (via conference call). Results indicated that overall reliability was low. All three panels reviewing non-CNS deaths agreed in only 36% of the cases (kappa = 0.21). Agreement among panels reviewing CNS deaths was somewhat higher at 56% (kappa = 0.40). Most of the disagreements, however, were in judging whether deaths were NP or POSS. Agreement was higher for early deaths and less severely injured patients. For non-CNS deaths agreement was also higher for younger patients. When both autopsy results and prehospital care reports were available reliability increased across panels. A variety of approaches have been used to elicit judgments of preventability. This study provides information to guide recommendations for future studies involving implicit judgments of preventable death. PMID- 1507297 TI - Lack of relevance of the Bohr effect in optimally ventilated patients with acute brain trauma. AB - The relationship between jugular bulb oxyhemoglobin saturation (SjO2) and oxygen tension (PjO2) during hyperventilation was prospectively evaluated in 37 adults with acute brain injuries. Hyperventilation was optimized in all patients, based on measured values of the arteriojugular oxyhemoglobin saturation difference, or cerebral extraction of oxygen (CEO2). Most patients initially had variable CEO2 values, in 578 observations carried out in the acute phase. Overall, there was a strong positive correlation between SjO2 and PjO2 at all levels of arterial pH. In 31 (5.3%) of the 578 observations, where the arterial pH was greater than 7.6, the SjO2 was disproportionally higher than the PjO2, despite a good SjO2-PjO2 correlation (moderate Bohr effect). In only 5 of these 31 observations (0.8%) did the SjO2 and PjO2 largely change in opposite directions (marked Bohr effect) during profound hypocapnia. The present findings support the current practice of continuous or intermittent SjO2 monitoring and management, and of optimized hyperventilation for control of intracranial hypertension, provided that hyperventilation is optimized according to the CEO2 values. Only on rare occasions (arterial pH greater than 7.6) is it advisable to replace SjO2 measurements by those of PjO2, because the latter is not affected by the Bohr effect. PMID- 1507298 TI - D-dimer levels correlate with pathologic thrombosis in trauma patients. AB - Pathologic thrombosis, in the form of pulmonary embolism (PE) and deep venous thrombosis (DVT), causes significant morbidity and mortality in trauma patients and presents a diagnostic and therapeutic challenge because of associated conditions in these patients. This study examines the measurement of D-dimer crosslinked fibrin degradation products (D-dimer XDPs) as an indicator of hypercoagulability that places a trauma patient at risk of developing pathologic thrombosis. The time course of changes in D-dimer values after trauma normally involves an initial increase with a rapid decrease of D-dimer XDP levels to normal. Patients who then demonstrate a second rise in D-dimer values are at risk for pathologic thrombosis. Forty-one trauma patients were studied, in two groups, to evaluate the potential use of D-dimer XDP levels in evaluating the risk of pathologic thrombosis. A secondary increase in D-dimer XDP levels was found to occur in patients with PE, although sepsis and adult respiratory distress syndrome can also cause a late increase. However, D-dimer determinations appear to provide an easy, relatively inexpensive means of evaluating trauma patients for the risk of pathologic thrombosis. PMID- 1507299 TI - Comparison between TRISS and ASCOT methods in controlling for injury severity. AB - ASCOT was developed by Champion et al. to address known limitations to TRISS. The present research attempted to validate ASCOT using an independent trauma registry. Data were collected by the Institute for Trauma and Emergency Care (ITEC), New York Medical College, between July 1, 1987 and June 30, 1989; 5685 trauma patients admitted to three level I trauma centers or five non-trauma center hospitals were included. Information was gathered by trained nurse abstractors using all available prehospital and hospital records. ASCOT and TRISS were compared using sensitivity, disparity, misclassification rates, and the Hosmer-Lemeshow goodness-of-fit statistics. Disparity and sensitivity rates were relatively low for both indexes, particularly among blunt injury patients. Total numbers of patients misclassified by TRISS and by ASCOT were similar; most misclassifications were made by both TRISS and ASCOT and involved nonsurvivors. Each method had advantages in predicting the outcomes of particular subgroups of patients; ASCOT with regard to predicting outcomes among patients with head injuries and in correctly classifying blunt injured patients; TRISS in correctly classifying survivors. We conclude (1) the relatively small gain in predictive accuracy by ASCOT over TRISS is largely offset by its complexity and increased computer processing requirements; (2) Hosmer-Lemeshow tests indicate that neither index provides good statistical agreement between predicted and actual outcomes among either blunt or penetrating injury patients. Future models should include additional variables, stratify patients by several injury causes, and use decision rules to select variables and variable weights. PMID- 1507300 TI - Coma in Mozambican gravidas: causes and perinatal outcome. AB - Ninety-one consecutive cases of coma were identified among gravidas at Maputo Central Hospital. The commonest causes were eclampsia (70 cases), cerebral malaria (six cases), and meningitis (five cases). Fetal mortality in eclampsia was 23 per cent and maternal mortality 10 per cent. There was a markedly higher incidence of eclampsia during the colder months. PMID- 1507301 TI - Use of a recombinant antigen (OC 3.6 cDNA) for the serological diagnosis of onchocerciasis in exposed Nigerian children. AB - We evaluated a recombinant antigen (OC 3.6 cDNA) expressed in pMAL TM vector for the diagnosis of onchocerciasis in children living in an endemic focus of forest type onchocerciasis in Nigeria. Using the Western blot with the maltose-binding fusion protein as antigen, 91 per cent of mf-positive children and 24 per cent of endemic normal children were positive. Furthermore, age was not a limitation to the assay. The practical limitations of the assay for field diagnosis of onchocerciasis is discussed. PMID- 1507302 TI - Early diagnosis of cystic fibrosis in Jordanian children. AB - Cystic fibrosis (CF) is the most common fatal genetic disease in childhood. The high infant mortality rate in Jordan and many other developing countries is mostly due to an increased prevalence of malnutrition, diarrhoeal diseases, and chest infections, which are also recognized clinical features of CF. Reports of CF among Arabs in neighbouring countries have stimulated clinical studies to evaluate the prevalence and incidence of this disease among Jordanian children. In a prospective study, 7682 neonates from 10 different hospitals in Jordan were screened for CF using the BM test for meconium albumin. Four cases gave a positive reaction to BM test strips. Cystic fibrosis was confirmed in three by sweat chloride test using pilocarpine iontophoresis. This represents an incidence of 1:2560 live births. In spite of the recognized limitations for the use of the BM test on meconium for mass screening of CF, this study has contributed to the increased awareness of the occurrence of CF among Jordanian children. PMID- 1507303 TI - Comparison of children and adults with tuberculous meningitis in Elazig, Turkey. AB - Retrospective evaluation of 16 cases of tuberculous meningitis revealed that BCG vaccination and tuberculin positivity were rare in pediatric as well as adult patients. Children with disease had developmental retardation and a high rate of maternal illiteracy as compared to normal controls. PMID- 1507304 TI - Chronic calcific pancreatitis in children. PMID- 1507305 TI - A comparative study of pulmonary function and body composition in Scottish and Libyan schoolchildren aged 12-17 years. PMID- 1507306 TI - Extra-pulmonary tuberculosis in BCG-vaccinated patients. AB - Six patients with extra-pulmonary tuberculosis who presented within a 2-year period to the Paediatric Department of the Faculty of Medicine, Galle, Sri Lanka, are presented. In spite of the BCG vaccination being given to all of them at birth, five patients subsequently developed miliary tuberculosis and one patient bone tuberculosis. The likely reasons for failure of BCG vaccination to prevent extra-pulmonary complications developing are discussed. PMID- 1507307 TI - Evaluation of risk factors for acute respiratory infections in under-five children in a transmigratory urban area at Bandung, Indonesia. The Respiratory Diseases Working Group. PMID- 1507308 TI - Pathogens in neonatalomphalitis. AB - During a 3-year study period, 33 neonates with omphalitis (with proven cultures) were encountered; aerobic and anaerobic cultures were obtained. An incidence of 2/1000 live births was recorded, with a high prevalence rate of 15.6/1000 admissions noted. Aerobes were isolated from 23 (70 per cent) specimens, whilst anaerobes were recovered alone in five (15 per cent) cases. There were 40 (1.2 per specimen) and 31 (0.9 per specimen) aerobic and anaerobic isolates, respectively. There was a significant detection of anaerobic pathogens such as the B. fragilis group (14), Gram-positive cocci (4) and Clostridium perfringens (3). Beta lactamase production was seen in 25 isolates, recovered from 25 newborns. PMID- 1507309 TI - Host factors and acute lower respiratory infections in pre-school children. AB - The relationship between certain host-related variables and the short-term outcome of hospitalization for severe acute lower respiratory infections was studied prospectively in a cohort of 103 pre-school Nigerian children. The respective mean ages of those with bronchiolitis and croup were 3.2 months and 18.9 months while the corresponding M:F ratios were 2.5:1 and 1:1. It was highly significant that all the eight children that died were malnourished (P less than 0.01). Furthermore, malnourished subjects with pleural effusion, in whom bacteraemia was common, stayed longest in hospital while subjects with bronchiolitis and croup, in whom malnutrition was distinctly uncommon, had the shortest duration of admission. Multiple microbial identifications and bacteraemia were common in malnourished subjects with ALRI. Mortality was significantly higher in older children (P less than 0.05), but sex, immunization/breast-feeding status and co-existing measles or pertussis, were individually neither related to the admission outcome nor the duration. It is concluded that malnutrition is a strong predictor of ALRI-related death in the pre-school child. The significance of bacteraemia and multiple microbial identifications in malnourished children, and the ARI-control implications of the study are discussed. PMID- 1507310 TI - Front-line epidemiology. PMID- 1507311 TI - Burkitt's lymphoma in an Indian child. PMID- 1507312 TI - Increased morbidity following acute viral hepatitis in children with glucose-6 phosphate dehydrogenase deficiency. PMID- 1507313 TI - Measles, mortality and malnutrition. PMID- 1507314 TI - Pattern of morbidity in pre-school children in rural Kerala. PMID- 1507315 TI - Cryptosporidium--an unrecognized enteropathogen. PMID- 1507316 TI - Quantitative determination of urinary marker proteins: a model to detect intrarenal bioeffects after extracorporeal lithotripsy. AB - To detect the source of relevant acute intrarenal side effects after extracorporeal piezoelectric lithotripsy and its impact on repeat treatment, urinary excretion of highly specific marker proteins was determined before (day 1) and after (days 0, 1, 4, 7, 14 and 21) treatment. Marker proteins included high molecular weight alpha-2-macroglobulin, immunoglobulin G, albumin, alpha-1 microglobulin as well as the enzyme N-acetyl-beta-glucosaminidase. Of 50 patients who underwent 4,000 shock waves to caliceal stones (group 1) 15 were identically retreated after 5 (group 2) or 15 (group 3) days, respectively, to determine the shortest safe interval to repeat extracorporeal piezoelectric lithotripsy. The course of lithotripsy damage was also evaluated in 15 pre-damaged kidneys (group 4). The alpha-2-macroglobulin enhancement found in all groups on day 0 (p less than 0.005 to p less than 0.05) documented intrarenal bleeding from ruptured vessels. Ratios of alpha-2-macroglobulin/albumin greater than 2.00 on days 0 and 1 exclude a glomerular source of gross hematuria (groups 1 to 4). There was only slight acute tubular damage after extracorporeal piezoelectric lithotripsy (N acetyl-beta-glucosaminidase increase, p less than 0.05 for groups 1 to 4). Retreatment after 5 days did not enhance the amount of proteinuria compared to the same patients from group 1 (statistically significant at p less than 0.45 to p less than 0.10). Group 3 also showed a similar elevation of proteinuria as the identical patients pretreated 15 days previously. Thus, the data seem to suggest that early repeat sessions of extracorporeal piezoelectric lithotripsy are as safe as delayed retreatments. The course of proteinuria in group 4 did not suggest enhancement of extracorporeal piezoelectric lithotripsy damage in pre injured kidneys. The urinary marker alpha-2-macroglobulin detects intrarenal vessel ruptures, which are responsible for intrarenal hematomas, as evidenced by animal and human histology. A model is offered to understand and detect the most important parenchymal bioeffects to minimize the risk of injury. PMID- 1507317 TI - Female fertility following extracorporeal shock wave lithotripsy of distal ureteral calculi. AB - This study was prompted by a spontaneous abortion in a 21-year-old woman following extracorporeal shock wave lithotripsy (ESWL ) of a distal ureteral calculus. To our knowledge, it is the first clinical retrospective study on the possible adverse effects of ESWL to the female reproductive tract. We analyzed treatment data and radiation exposure of 84 women in the reproductive period, and surveyed the patients by questionnaire, to which 67 (79.8%) responded. After ESWL 57 women (85.1%) practiced some form of contraception, while 10 childless women attempted to become pregnant. Overall 7 children with no malformations or chromosomal anomalies were born to 6 patients. Miscarriages were noted in 3 patients (4.5%) but they occurred at least 1 year after ESWL. Our data suggest that ESWL of lower ureteral calculi is a safe and effective procedure, and does not affect female fertility or lead to increased teratogenic risk. PMID- 1507318 TI - Long-term followup after extracorporeal shock wave lithotripsy treatment of kidney stones in solitary kidneys. AB - A total of 64 treatments by the Dornier HM3 lithotriptor was performed on 52 solitary kidneys with stones. A slight increase but no significant variations in serum creatinine was noted in 15 patients without obstruction just after treatment (p greater than 0.05). No significant increases in serum creatinine were found even at the short-term, mid-term and long-term followup. After 12 to 56 months hypertension developed in only 1 previously normotensive patient. Of 37 patients at mid-term followup (12 to 24 months) 62% were stone-free, 24% had passable fragments, 8% had recurrent stones and 5% had regrowth of the residual fragments. At long-term followup (24 to 56 months) 50% of 26 patients were stone free, 19% had dust or passable fragments, 19% had recurrences and 11% had regrowth of the residual fragments. The demonstrated effectiveness, small number of complications at the short-term followup, lack of sequelae at the long-term followup and relatively small number of recurrences confirm that extracorporeal lithotripsy is not only effective but also safe. It can be proposed as the treatment of first choice even when the stone is in a single remaining kidney. PMID- 1507319 TI - Use of radionuclide renal imaging for clinical followup after extracorporeal shock wave lithotripsy of renal stones. AB - Patients treated by extracorporeal shock wave lithotripsy (ESWL) are usually evaluated by excretory urography within 1 month after treatment to determine the clearance of stone debris and rule out asymptomatic obstruction. In an attempt to obtain more precise functional information, we used 99mtechnetium diethylenetriaminepentaacetic acid and 131iodine-hippurate radionuclide renal imaging studies, and a plain abdominal radiograph as the initial followup study after ESWL of 64 kidneys in 55 patients. Of 53 kidneys studied within 60 days after ESWL 42 had abnormal radionuclide renal imaging studies demonstrating pelviocaliceal stasis, excretory delay or poor function, 8 of which required subsequent interventions for obstructing stone debris. Five patients had excretory delay after ESWL that was unexpected based on a pre-ESWL excretory urogram showing normal function without dilation. A subset of 23 patients with large stone burden or anatomical deformity from a prior operation had baseline radionuclide renal imaging studies before ESWL; function improved in 4 and worsened in 5 by radionuclide renal imaging studies after completion of treatment. A total of 19 patients had radionuclide renal imaging studies earlier (within 17 days) after ESWL because of poor function and/or large stone burden, and as expected they had evidence of obstruction from stone debris, which necessitated further followup. Our experience suggests that followup of ESWL by radionuclide renal imaging studies provides specific functional information that is of particular value in the management of patients with obstructing stone debris and/or diminished renal function. Radionuclide renal imaging studies may also reveal unsuspected obstruction or functional impairment after ESWL of uncomplicated stones, and is recommended as routine followup after ESWL. PMID- 1507320 TI - 111Indium-oxine-labeled leukocytes and 67gallium-citrate as indicators of renal injury following extracorporeal shock wave lithotripsy. AB - To document the extent and persistence of traumatic inflammation after extracorporeal shock wave lithotripsy (ESWL), 15 patients were randomly chosen to have either 67gallium (67Ga)-citrate or 111indium (111In)-oxine scans within 24 to 48 hours of ESWL. Positive scans were repeated at 8 to 12 weeks. Nine patients had renal calculi, and 6 had ureteral calculi and acted as controls. Of the patients with renal calculi 6 were scanned with 67Ga-citrate and 3 with 111In oxine. Four of the former and 2 of the latter scans showed evidence of renal injury. Followup scans were normal. There was no correlation between power index (number of shocks times accelerating voltage) and scan results. Half of the control subjects were scanned with 67Ga-citrate and the remainder with 111In oxine and all scans were negative. 67Ga-citrate and 111In-oxine scans can show evidence of renal injury immediately after ESWL but abnormal scans 2 to 3 months later would be suggestive of a different inflammatory process. PMID- 1507321 TI - Bioeffects of extracorporeal shock wave lithotripsy: a worry or not? PMID- 1507322 TI - Stone surface area determination techniques: a unifying concept of staghorn stone burden assessment. AB - The use of stone surface area measurements obtained from standard radiographs provides a more accurate and reproducible assessment of stone burden when reporting results and treatment recommendations for staghorn calculi. Techniques for determining stone surface area include use of graph paper, planimeter or computerized image analysis. The use of graph paper is inefficient while planimeters suffer from significant variation for areas less than 500 mm.2 (more than 5%). Computer image analysis is accurate, rapid and easiest to perform. Software programs compatible with microcomputers are readily available making assessment of stone surface area practical and inexpensive. Stone surface area showed close correlation to stone volume as measured by 3-dimensional computerized tomography (correlation coefficient 0.84, p = 0.005). Stone surface area determination enables more accurate reporting of treatment results and, thus, recommendations based upon stone burden. Comparison of data between institutions becomes more meaningful if stone surface area is used. Stone surface area also provides a useful basis to study and compare trends of treatment within a single institution. PMID- 1507323 TI - Anesthesia and complications of extracorporeal shock wave lithotripsy of urinary calculi. AB - The techniques of anesthesia for extracorporeal shock wave lithotripsy of urinary calculi and the associated complications in 600 treatments with the second generation lithotriptor Siemens Lithostar were studied. General anesthesia was used in 17 treatments (2.8%) and epidural anesthesia was applied in 73 (12%), primarily in children and patients in need of simultaneous surgical auxiliary procedures. A total of 510 treatments (85%) was performed with a combination of local infiltration anesthesia and supplementary intravenous opiates. In 65% of the cases only 2 injections of opiates were sufficient for pain relief. There were no complications in 394 treatments (77%) and minor complications, such as arrhythmia (9.2%) and nausea/vomiting (7.6%), were easily treated. Respiratory depression was observed in 10 cases (2%) and this potentially dangerous complication was associated with simultaneous administration of opiates and midazolam. Only 9 treatments (1.8%) had to be terminated due to complications. It is concluded that most treatments of urinary calculi with this second generation extracorporeal shock wave lithotriptor can be performed with local infiltration anesthesia combined with supplementary short-acting opiates intravenously for pain relief and sedation. When administering supplementary midazolam for sedation the risk of respiratory depression should be considered. PMID- 1507324 TI - The use of an abdominal compression belt to reduce stone movement during extracorporeal shock wave lithotripsy. AB - We used an abdominal compression belt in 50 patients undergoing extracorporeal shock wave lithotripsy with the Siemens Lithostar lithotriptor to limit diaphragmatic excursion and, therefore, renal calculus movement. Stone movement was measured on the monitor with and without the compression belt. Abdominal compression was found to decrease the range of stone movement by an average of 32% (-4 to 63%). This technique was less effective in patients with limited chest expansion. Abdominal compression was also found to be useful during treatment of renal and upper ureteral stones in reducing overall patient movement. The decreased stone movement during extracorporeal shock wave lithotripsy with abdominal compression may increase stone fragmentation and may decrease the number of shocks per treatment. PMID- 1507325 TI - The use of a cystoscopically placed cobra catheter for directed irrigation of lower pole caliceal stones during extracorporeal shock wave lithotripsy. AB - As the general experience with extracorporeal shock wave lithotripsy (ESWL) for renal calculi broadens, it is increasingly evident that the clearance of stone fragments in lower pole calices needs to be improved. The stone-free rate after treatment for lower caliceal stones is consistently less than that for other upper tract locations. Use of a cystoscopically placed cobra catheter for directed irrigation during ESWL resulted in an increase of our lower caliceal stone-free rate at 1 and 3 months of followup to 71% (15 of 21) compared to 33% (8 of 24) of randomly selected controls at 1 month and 54% (13 of 24) at 3 months. We conclude that pre-ESWL placement of a cobra catheter into the lower pole calix and intermittent irrigation during the procedure are potentially useful adjuncts in the successful treatment of lower caliceal calculi. PMID- 1507326 TI - Extracorporeal shock wave lithotripsy retreatment ("stir-up") promotes discharge of persistent caliceal stone fragments after primary extracorporeal shock wave lithotripsy. AB - A prospective randomized study was performed to compare the results of piezoelectric extracorporeal shock wave lithotripsy (ESWL) retreatment versus surveillance only in 50 patients with persistent caliceal stone fragments after primary ESWL for renal calculi. After a 3-month followup significant decreases in residual debris were observed in the retreated group, while changes in the control group were negligible. Considering the low morbidity of outpatient ESWL with a pain-free, second generation lithotriptor, ESWL retreatment of completely fragmented but persistent stone debris appears to be justified to render the kidney stone-free. PMID- 1507327 TI - Treatment of caliceal diverticular calculi with extracorporeal shock wave lithotripsy: patient selection and extended followup. AB - We treated 19 selected patients with calculi in 21 caliceal diverticula with extracorporeal shock wave lithotripsy (ESWL). By limiting this treatment to patients with relatively small (less than 1.5 cm.) calculi associated with a radiographically patent diverticular neck, a stone-free state was initially achieved in 11 patients (58%). Of 14 patients with flank pain before ESWL 12 (86%) were rendered symptom-free or markedly improved, often independent of a stone-free state. Extended followup in 13 patients for 12 to 49 months (mean 23.8 months) after ESWL revealed recurrent stones or stone growth in only 1. Although pain relief has remained constant for those initially rendered symptom-free, recurrent infection has been documented in 6 (67%) of 9 patients with infection before ESWL. We conclude that ESWL for selected patients with calculi in caliceal diverticula can achieve a relatively high initial stone-free rate and that recurrent stones may not be inevitable. Treatment in this setting also may provide long-term symptomatic relief that is often independent of a stone-free state. However, recurrent infection is not unusual, especially when associated with residual calculi. Considering the relatively noninvasive nature of this approach, ESWL should be considered an acceptable form of primary management for selected patients with calculi in caliceal diverticula. PMID- 1507328 TI - Clinical trials of the Northgate SD-3 dual-purpose lithotriptor for renal calculi. AB - The Northgate SD-3 is a bathless, portable shock wave lithotriptor made in the United States. It uses ultrasound localization and spark-gap, electrode-generated shock waves to fragment calculi in the upper urinary tract. Since October 1987, 312 treatments have been performed on 281 patients (286 kidneys) with stone burdens less than 2 cm. during clinical trials at 6 investigational sites in the United States. A fragmentation rate of 94% was achieved. Of the treatments 78% were judged successful (stone-free or fragments of less than 5 mm. remaining in an asymptomatic patient) and a 3-month stone-free rate of 58% was noted. The retreatment rate was 9% and the ancillary procedure rate was 5%. The complications (hematuria, ecchymosis, pain, obstruction) were mild and not unlike those seen in patients undergoing lithotripsy with other devices. PMID- 1507329 TI - Efficacy of second generation lithotriptors: a multicenter comparative study of 2,206 extracorporeal shock wave lithotripsy treatments with the Siemens Lithostar, Dornier HM4, Wolf Piezolith 2300, Direx Tripter X-1 and Breakstone lithotriptors. AB - Extracorporeal shock wave lithotripsy (ESWL) has become the treatment of choice for urinary calculi. The good results of the first generation Dornier HM3 lithotriptor stimulated the development of second generation machines. A multicenter trial is presented involving the Siemens Lithostar, Dornier HM4, Wolf Piezolith 2300, Direx Tripter X-1 and Breakstone lithotriptor to compare the therapeutic efficacy of second generation machines. Treatment results were best for calculi less than 2 cm. in diameter. Although the second generation lithotriptors are comparable to each other, none of the machines provided a success rate comparable to that of the first generation unmodified Dornier HM3 lithotriptor. The 5 machines differed mainly in types of stones treated in relation to imaging system, use of anesthesia, use of auxiliary procedures and hospitalization but overall success rates were similar. We conclude that second generation ESWL is less effective than first generation ESWL. PMID- 1507330 TI - Evolution of the technique of combination therapy for staghorn calculi: a decreasing role for extracorporeal shock wave lithotripsy. AB - Percutaneous nephrostolithotomy with or without extracorporeal shock wave lithotripsy (ESWL) has been extensively used in the management of staghorn calculi, with stone-free rates varying from 23 to 86%. Explanations for the variability of such results include differences in stone burden, differences in percutaneous techniques and an overreliance on ESWL. The results and changing trends in the relative roles of percutaneous nephrostolithotomy and ESWL in the management of staghorn calculi at the Methodist Hospital of Indiana were examined. We reviewed 343 cases of staghorn calculi (partial and complete) with adequate followup data, which were managed with initial percutaneous nephrostolithotomy. Cases were divided into 2 groups: group 1 (252 cases) from 1984 to 1987 when access was performed by a radiologist and group 2 (91 cases) from 1988 to 1990 when access was performed by a urologist. Although stones in group 2 tended to be larger, a decreasing dependence on ESWL was noted (64.7% in group 1 compared to 35.2% in group 2, p less than 0.001). Despite the larger stone size in group 2, stone-free rates were similar (83.3% in group 1, 86.8% in group 2). In groups 1 and 2 percutaneous nephrostolithotomy alone achieved stone free rates of 91% and 91.5%, respectively. The stone-free rate with the combination approach was 79.1% and 78.1% in groups 1 and 2, respectively. Technical refinements with percutaneous nephrostolithotomy in group 2 include accurate and carefully selected accesses (superior pole in 36.3%) for best approach to the stone, multiple accesses (13.3%) and improved skills in flexible nephroscopy. Blood transfusion has not been required in group 2 compared with 11.1% in group 1. Mean hospital stay was 12.4 days in group 1 and 10.3 days in group 2 (percutaneous nephrostolithotomy alone, 7.2 days). With careful attention to percutaneous nephrostolithotomy techniques, complex renal stones can be successfully managed endourologically, reducing the need for combination ESWL. Complications previously associated with percutaneous nephrostolithotomy have decreased. PMID- 1507331 TI - Evolution of shock wave lithotripsy during its first decade. PMID- 1507332 TI - Effect of extracorporeal shock wave lithotripsy on renal function and body height in pediatric patients. AB - Although extracorporeal shock wave lithotripsy (ESWL) is the preferred modality for treatment of most renal and upper ureteral calculi in adults, little is known about its effect on the pediatric population. We carefully followed 12 children 2.2 to 15.3 years old (mean age 9.4) treated with the Dornier HM3 lithotriptor. Effective renal plasma flow was obtained by quantitative 131iodine hippurate scan immediately preceding ESWL and at followup (range 74 to 238 weeks, mean 149). The treated kidney received an average of 1,702 shocks (range 1,000 to 2,200). Mean effective renal plasma flow increased in the treated kidney from 185 cc per minute before ESWL to 217 at followup (p = 0.016) and in the untreated kidney from 191 to 224 (p = 0.0013). Total effective renal plasma flow increased from 376 cc per minute before ESWL to 440 at followup (p = 0.0019). In the treated kidney mean and total effective renal plasma flow increased by 31 (expected 32) and 64 (expected 68) cc per minute, respectively, while in the nontreated kidney mean effective renal plasma flow increased by 33 (expected 36) cc per minute. None of the observed changes in effective renal plasma flow was significantly different from the expected changes using the paired t test at the 95% level. In addition, change in body height was evaluated using standard deviation scores. Mean body height (standard deviation) before ESWL was -0.39 (range -3.2 to 2.0) and at last followup it was -0.26 (range -2.6 to 2.4), which is not statistically significant (p = 0.37). Although these patients continue to be followed and caution is advised, this long-term study indicates that ESWL within the range of shocks delivered to this cohort does not statistically affect linear growth (body height) or renal function in the pediatric population. PMID- 1507333 TI - Percutaneous nephrolithotomy in children. AB - Percutaneous nephrolithotomy was performed on 18 children with renal calculi. No mortality resulted from this procedure and hemorrhage was the major complication. At the end of treatment 67% of the patients were stone-free and 82% of targeted stones were removed. Percutaneous nephrolithotomy can be considered a successful treatment in the management of the pediatric patient with renal calculi. PMID- 1507334 TI - Percutaneous management of urolithiasis during pregnancy. AB - A total of 6 pregnant women with obstructing urinary calculi was managed by percutaneous nephrostomy drainage placed under ultrasound guidance with the patient under local anesthesia. All patients initially had relief of acute obstruction. However, occlusion of the percutaneous nephrostomy tubes with debris necessitated tube changes in 5 of 6 patients. In 2 patients recurrent nephrostomy tube obstruction, fever and pain led to percutaneous stone removal during pregnancy. In the remaining 4 patients the nephrostomy tubes were left indwelling through delivery. During the postpartum period 3 patients successfully underwent ureteroscopic stone extraction and 1 passed the stone spontaneously. Bacteriuria developed in each patient despite the use of preventive antibiotics. All 6 women had uncomplicated vaginal deliveries of healthy newborns and are currently asymptomatic with no evidence of obstruction. Percutaneous drainage of an acutely obstructed kidney in a pregnant woman is an effective temporizing alternative to ureteral stent placement until definitive treatment can be performed. PMID- 1507335 TI - Management of urinary calculi during pregnancy. AB - Renal calculous disease is an infrequent but not insignificant occurrence during pregnancy. In 50 to 80% of the cases conservative management is appropriate and the stone will pass spontaneously. Should intervention be required, recent advances in stone management and techniques for urinary tract drainage may be successfully applied to the obstetric population. Concerns regarding surgical and anesthetic risks, and the potential hazards of radiation exposure during pregnancy favor a minimally invasive approach with definitive treatment late in pregnancy or post partum. We review our experience during a 5-year period in managing 29 patients with urinary calculous disease during pregnancy. Based on our experience and review of the literature an algorithm for treatment of urolithiasis during pregnancy is proposed. PMID- 1507336 TI - Stones in pregnancy and in children. PMID- 1507337 TI - Mechanisms responsible for diminished fragmentation of ureteral calculi: an experimental and clinical study. AB - We molded 24 synthetic stones (mean weight 680 mg., range 641 to 715) from a commercial mixture of gypsum, silica, cellulose and polyvinyl acetate. Each stone was subjected to 400 shocks on a Wolf 2300 Piezolith and groups of 6 stones were treated in 4 different modes. Mean amounts fragmented were 243 +/- 18 mg. in a free environment, 62 +/- 18 mg. confined loosely in a latex tube, 22 +/- 8 mg. impacted in the tube and 30 +/- 8 mg. impacted alongside a 7F stent. During a 30 month period 118 patients received in situ extracorporeal shock wave lithotripsy for ureteral calculi using the same lithotriptor. The mean stone burden was 11.4 mm. (range 4 to 29). Success was greater for patients with calculi 10 mm. or less than for those with stones greater than 10 mm. (71% versus 51%, p less than 0.05), despite the former group receiving less shocks (5,404 versus 7,491). The influence of size was then excluded by studying the number of shocks delivered per mm. of calculus. Patients receiving 500 to 699 shocks per mm. showed a higher success rate than those receiving a smaller number of shocks per mm. Treatment with a greater number of shocks per mm. did not improve success rate. The experimental study demonstrated that confinement and impaction significantly diminish the rate of fragmentation of calculi. However, the clinical study suggested that there may be an optimum number of shocks per mm. that should be delivered. Treatment beyond this point fails to improve results. The 28% failure rate even in those receiving the highest number of shocks per mm. suggests that large, impacted calculi are unsuitable for treatment with in situ shock wave lithotripsy on this machine. PMID- 1507338 TI - Sonographic detection of ureteral calculi in patients with normal excretory urography. AB - We report 3 cases of nonobstructing distal ureteral calculi diagnosed by sonography in which excretory urography was normal. In each case sonography was performed because of high clinical suspicion for a ureteral stone. In 2 patients a stone was impacted at an edematous ureteral orifice. All 3 patients subsequently passed the stone spontaneously. A high resolution ultrasound examination should be performed on patients with a history suggestive of ureteral calculus despite a normal excretory urogram. PMID- 1507339 TI - Management of ureteral stones by extracorporeal shock wave lithotripsy using Lithostar lithotriptor. AB - In 282 patients 290 ureteral stones were treated with extracorporeal shock wave lithotripsy using the Lithostar lithotriptor. Stones were in the upper ureter in 198 units (68.3%), middle ureter in 36 (12.4%) and lower ureter in 56 (19.3%). The average stone mass was 11.9 mm. and the mean number of shock waves was 4,913 for all levels with a mean kv. of 16.9. The average number of sessions was 1.5 for all sites. Auxiliary measures in the form of ureteral catheterization were done in 24 patients (8.5%) and internal stenting in 12 (4.25%), all of whom had upper or middle ureteral stones. Disintegration of the stones was achieved in 99% of the upper, 93.7% of the middle and 91.7% of the lower ureteral stones. However, clearance of fragments within 3 months from the last session was achieved in 94.8% of the upper, 87.5% of the middle and 91.7% of the lower ureteral stones for an overall stone-free rate of 93.3%. PMID- 1507340 TI - The Swiss Lithoclast: a new device for intracorporeal lithotripsy. AB - Modalities available for performing intracorporeal lithotripsy include ultrasonic, electrohydraulic and laser procedures. We present our experience with a new and unique technology for performing intracorporeal lithotripsy, namely the Swiss Lithoclast. This simple and inexpensive device uses compressed air to activate a solid probe in a manner similar to that of a jackhammer. We report the use of the Lithoclast in 31 cases, consisting of 6 renal calculi approached percutaneously, 17 ureteral calculi and 8 bladder calculi. The Lithoclast successfully fragmented 94% of the calculi. There were no intraoperative or long term complications directly related to the use of this device. We have found the Swiss Lithoclast to be a safe, effective and inexpensive means of performing intracorporeal lithotripsy for calculi located throughout the urinary tract. PMID- 1507341 TI - Cost and efficacy of extracorporeal shock wave lithotripsy versus ureteroscopy in the treatment of lower ureteral calculi. AB - We retrospectively reviewed the extracorporeal shock wave lithotripsy (ESWL) and ureteroscopy experience relative to cost and efficacy of a group of practitioners skilled in the use of both procedures for the treatment of lower ureteral stones. Although the initial success rate was higher with ureteroscopy, no significant difference could be found in final success or complication rates. The cost of ESWL was approximately 60% higher than that for ureteroscopy (mean $7,320.26 versus $4,568.47, p less than 0.005). Given the current restraints on resources, and the equal efficacy and morbidity of both procedures, ureteroscopy must be considered the procedure of choice in the management of lower ureteral stones. PMID- 1507342 TI - In situ extracorporeal shock wave lithotripsy of ureteral calculi with the MPL 9000X lithotriptor. AB - Within the wide armamentarium of urinary stone treatment modalities extracorporeal shock wave lithotripsy (ESWL) has been established as the first line procedure. With the Dornier MPL-9000X lithotriptor one has the choice of ultrasound or fluoroscopic localization of calculi throughout the entire urinary tract. Except for the kidney, ultrasound guidance is preferred for calculi in the distal ureter, while fluoroscopy is generally used on the proximal two-thirds of the ureter. Between January and December 1990, 123 ESWL treatments were performed on 83 patients suffering from ureteral calculi with an average stone size of 9.3 x 6 mm. Median treatment parameters were 1,597 shock waves at 19.3 kv. for 43 minutes. For stones in the upper two-thirds of the ureter sedation analgesia was given, while ESWL on the pelvic ureter did not create intolerable pain. Of the treatments 69% were done on an outpatient basis. In situ ESWL treatment of urinary calculi was successful in 72 patients (86.7%), and 20 patients (24.1%) were treated with multiple treatment sessions. ESWL therapy for 47 stones in the distal ureter showed better results than for 33 stones plus 2 steinstrasse in the proximal part (95.5% versus 80% stone-free rate). Of 4 patients with mid ureteral calculi 2 could be rendered stone-free by ESWL alone. Auxiliary procedures, such as percutaneous nephrostomy or ureteral splints, had to be performed in 15.7%. Final endoscopic stone extraction was done in 7 cases and open surgery in 4, constituting a 13.3% failure rate for ESWL therapy. The results prove that the MPL-9000X lithotriptor is effective for primary noninvasive stone treatment. PMID- 1507343 TI - Management of ureteral calculi: the debate continues... PMID- 1507344 TI - Percutaneous management of a nephrocutaneous fistula due to a pyelocaliceal diverticular calculus. AB - Nephrocutaneous fistulas arising from stone-containing pyelocaliceal diverticula are rare. We describe 2 patients who were treated by open drainage for perirenal abscesses. Subsequently, both patients presented with a nephrocutaneous fistula from a stone-containing pyelocaliceal diverticulum. These patients were successfully treated by percutaneous nephrostolithotomy with fulguration of the diverticula. PMID- 1507345 TI - Endoscopic and open stone surgery in morbidly obese patients. AB - Management of urinary stone disease in the morbidly obese patient can be troublesome and problematic. We present 4 recent female patients with an average weight of 442 pounds and an average height of 5 feet 2 inches. The patients underwent a total of 8 open surgical or endoscopic procedures for partial or complete staghorn calculi. Complications encountered included inability to reach the stones with rigid or flexible ureteroscopes, inadvertent incision above the 10th rib for pyelolithotomy, intraoperative rhabdomyolysis during a flank incision, consecutive temporary renal failure and wound infection. We discuss the limitations of extracorporeal shock wave lithotripsy, retrograde endoscopic manipulation, percutaneous antegrade surgery and open surgical approaches. Such patients continue to represent diagnostic challenges and high risk therapeutic options. PMID- 1507346 TI - Extracorporeal shock wave lithotripsy of radiolucent urinary calculi using the Siemens Lithostar Plus. AB - Between October 1989 and June 1991, 1,250 patients with urinary calculi were treated at our institution using the Siemens Lithostar. A total of 17 patients (1.37%) with radiolucent or slightly opaque calculi underwent lithotripsy with the Lithostar Plus, which has an overhead electromagnetic generator module and a localization system composed of a real-time on-line 3.5 mHz. ultrasound transducer. The stones were located in the calices in 52.9% of the cases, renal pelvis in 17.7%, ureter in 23.5% and bladder in 5.9%. Followup consisted of a nephrotomogram or ultrasound 1 day and 1 to 3 months postoperatively. Complete removal of all stone fragments was achieved in 76.4% of the cases after 3 months. Retreatment was necessary in 23.5% of the cases. All treatments were performed without anesthesia and hospitalization. Complications were present in 11.8%; perirenal hematoma was noted in 1 patient but this resolved spontaneously within a few days and the same occurred in 1 patient with renal pain. Extracorporeal shock wave lithotripsy using the Lithostar Plus proved to be an effective noninvasive procedure to treat radiolucent and slightly opaque urinary calculi. However, since the Lithostar Plus has a higher power setting, care must be taken to avoid damage with the use of high energy. PMID- 1507347 TI - An evaluation of 646 stone patients treated on the HM4 extracorporeal shock wave lithotriptor. AB - Extracorporeal shock wave lithotripsy (ESWL) has become the preferred treatment modality for the majority of urinary tract calculi. This form of treatment boasts excellent patient acceptance and has significantly reduced the need for surgical intervention. An evaluation of our first 646 patients undergoing 722 ESWL treatments at Walter Reed Army Medical Center revealed an overall stone-free rate at 1 and 3 months of 52% and 79%, respectively. The exact location of each stone within the kidney and ureter further determined the stone-free rates at 1 and 3 months. Stone-free rates at 3 months ranged from 89% for renal pelvic stones to 64% for lower pole caliceal stones. Upper third ureteral stones treated in situ without stenting resulted in a 74% stone-free rate at 3 months. This rate increased to 85% when these patients were stented and treated in situ. Although statistically insignificant, when the upper third ureteral stones were manipulated into and treated in the renal pelvis (31% of our patient population) the 3-month stone-free rate increased to 87%. Attempts were made to stent all ureteral stones before treatment. The stone-free rate at 3 months was 86% for mid third ureteral stones and 81% for lower third ureteral stones. The overall retreatment rate was 11.8% with a complication rate of 7.6% and a 6.3% post-ESWL intervention rate (open or percutaneous surgery, stent or percutaneous nephrostomy placement). PMID- 1507348 TI - Electromagnetic extracorporeal shock wave lithotripsy for calculi in horseshoe kidneys. AB - Between June 1987 and January 1991, 11 renal units in 10 patients with horseshoe kidneys were managed by electromagnetic extracorporeal shock wave lithotripsy (ESWL) monotherapy with a Siemens Lithostar. A total of 33 calculi was treated in 42 sessions. All treatments were performed without anesthesia and on an outpatient basis. All calculi could be targeted by standard installation techniques. The maximum number of shock waves per session was 4,000, which implies per stone an average of 1.3 sessions and an average of 4,903 shock waves (range 1,800 to 9,000) at a mean energy setting of 17.8 kv. Complete disintegration or fragmentation into spontaneously passable particles was achieved in 27 calculi, for a success rate of 83% when considering the results in regard to the individual stone locations. Per renal unit, an average of 3 calculi were targeted and after an average of 3.8 sessions 6 units became stone-free. Horseshoe kidneys, when calculous, contain dispersed and multiple calculi and from these data approximately 1 session per stone must be planned. The number of treatments per renal unit increased in proportion to the number of calculi and to the presence of calculi with low fragility. Of 21 lower pole calculi 18 completely evacuated and this observation has been related to the more medial location of the inferior calices near the ureteropelvic junction. No impaired drainage of fragments was noted to be related to the horseshoe anatomy. Patency of the ureteropelvic anatomy appeared to be the main parameter for the evacuation of fragments. Neither preoperative nor postoperative adjuvant maneuvers have been necessary. PMID- 1507349 TI - Extracorporeal shock wave lithotripsy and endoscopic management of renal calculi with urinary diversions. AB - A total of 12 patients with urinary diversions had calculi in 15 kidneys managed initially by extracorporeal shock wave lithotripsy (ESWL) in 12 kidneys and percutaneous nephrolithotripsy in 3. After 15 treatments with ESWL only 3 of the 12 kidneys (25%) became stone-free. Endoscopic procedures were used in 5 kidneys with fragments remaining after ESWL, and comprised percutaneous ultrasound lithotripsy in 2 and transstomal retrograde manipulations in 3. The 3 initial and 5 subsequent endoscopic procedures resulted in 6 of the 8 kidneys (75%) being stone-free. The poor results with ESWL are due to preexisting dilated upper urinary tracts and to immobility in obese myelomeningocele patients. Endoscopic procedures are the preferred method of treatment in these patients. PMID- 1507350 TI - Urinary tract status of patients with neurogenic dysfunction presenting with upper tract stone disease. AB - We treated 71 patients with neurogenic vesical dysfunction between September 1983 and June 1990 for upper tract stones. We studied these patients to determine the time course of stone development and the presence of associated urological abnormalities. There were 44 male and 27 female patients 6 to 72 years old. Lower urinary tract dysfunction resulted from spinal cord injuries in 34 patients (48%), myelodysplasia in 19 (27%), multiple sclerosis in 12 (17%) and other diagnoses in 6 (8%). Of 71 patients 21 (30%) were managed by an ileal loop, 12 (17%) by a Foley catheter, 10 (14%) by a suprapubic tube, 10 (14%) by ureterostomy, 5 (7%) by vesicostomy, 8 (11%) by intermittent catheterization, and 5 (7%) by diaper, Crede's voiding or condom catheterization. Stone disease developed within 1 to 22 years. Patients with an indwelling catheter or supravesical diversion fared worse than those managed by intermittent catheterization or vesicostomy; they had higher rates of renal unit loss, renal parenchymal damage, decreased renal function, hydroureter, and staghorn and bilateral calculi. All of the listed methods of management were contemporaneous, suggesting the continued use of methods proved to be associated with upper tract deterioration. PMID- 1507351 TI - Multiple large calculi in a continent urinary reservoir: a case report. AB - Continent urinary reservoirs have increasingly become popular during the last decade but they are associated with long-term complications. We report a case of huge multiple stones in an ileocecal reservoir, which formed as a result of noncompliance with intermittent self-catheterization. An open method was required for removal of the stones to prevent recurrent urosepsis. PMID- 1507353 TI - Special issue: Calculi. PMID- 1507352 TI - Stone therapies. PMID- 1507354 TI - Urolithiasis complicating inflammatory bowel disease. PMID- 1507355 TI - The effects of a single evening dose of alkaline citrate on urine composition and calcium stone formation. AB - The effects on urine composition and pH of a single evening dose of alkaline potassium sodium citrate were studied in healthy subjects and recurrent calcium oxalate stone formers. This treatment resulted in a prompt and significantly increased urinary pH with a duration until 10 a.m. the next day and a reduced risk of calcium oxalate crystallization between 10 p.m. and 10 a.m. In a retrospective study alkaline citrate was given in a single evening dose of 3.75 or 5 gm. to 55 patients with calcium oxalate stone disease and a total dose of 5.0 or 7.5 gm. was administered 2 or 3 times daily in 17 patients. The mean plus or minus standard deviation for duration of treatment was 3.5 +/- 1.7 years. Significantly reduced stone formation was recorded only in those on the evening dose regimen, which was associated with significant improvement of urine composition. Patients who continued to form new stones or who had growth of residual stones despite treatment also had improved urine composition but the calcium excretion and the calcium/citrate quotient remained elevated. In 4 patients with new stone formation calcium phosphate was the major component and calcium excretion was high but the concomitant increased citrate excretion resulted in a calcium/citrate quotient that was only slightly elevated. In patients forming calcium oxalate stones the only abnormality was a high calcium/citrate quotient. Because of favorable biochemical and clinical effects as well as good patient compliance with a single evening dose of alkaline citrate, this regimen appears to be an attractive alternative for long-term prevention of recurrent calcium stone formation. PMID- 1507356 TI - Plasma and urine glycolate assays for differentiating the hyperoxaluria syndromes. AB - To differentiate hyperoxaluria syndromes we measured plasma and urine glycolate by a novel high performance liquid chromatographic procedure. Mean glycolate level was 7.9 +/- 2.4 mumol./l. in plasma and 422 +/- 137 mumol./24 hours in urine from 19 control subjects. Renal clearance was about 50% the glomerular filtration rate irrespective of the underlying disease. There was close correlation between glycolate and oxalate in plasma. Plasma glycolate was normal in all but 8 patients who had primary hyperoxaluria 1. Plasma assay detected the disease more efficiently than urine assay. Pyridoxine decreased oxalate biosynthesis in 2 of the 4 patients treated with it and glycolate assay confirmed this behavior. Glycolate excretion was significantly high in 3 of 8 patients of primary hyperoxaluria 1 patients. Idiopathic stone formers had mild increases in glycolate excretion but this was not related with oxalate excretion. Glycolate levels were normal in 5 patients with enteric hyperoxaluria. We conclude that glycolate assay is essential for identifying patients with primary hyperoxaluria 1 and may represent a valuable tool for differentiating hyperoxaluria. PMID- 1507357 TI - Calcium oxalate crystallization properties in urine with different specific electrical conductivities. AB - The relationship between the degree of urine dilution and the risk of calcium oxalate crystallization was studied in 32 urine samples collected from stone formers and normal subjects during an 8-hour period between 10 p.m. and 6 a.m., and in 4-hour urine samples collected during 24-hour periods from 6 patients with calcium stone disease. The risk of calcium oxalate crystallization was analyzed in terms of the increase in oxalate concentration required for a standardized precipitation of crystals of calcium oxalate. The degree of urine dilution was determined with a new instrument (urimho) designed for measuring the concentration, in terms of specific electrical conductivity, in urine samples of droplet size. With this device urine concentration can be expressed in urimho values between 1 and 5. There was a good correlation between recordings of specific electrical conductivity performed with the new device and with a conventional conductivity meter. There was a statistically significant positive correlation between urimho values and calcium oxalate crystallization. Calcium oxalate crystallization greater than 1.3 was not observed in any sample with a urimho value of 2 but it was noted in 31% of the samples with urimho values greater than 2. A positive relationship was also recorded between the urine pH and the urimho level, which is noteworthy because there was an inverse relationship between urine pH and calcium oxalate crystallization. A pH greater than 6 was observed in 78% of the samples with a urimho value of 2 but it was noted in only 27% of the samples with urimho readings between 3 and 5. A considerable variation in the response in urinary flow to ingested volumes was recorded. Therefore, monitoring of urine dilution by means of a sample device like the urimho might be of great help for patients with calcium stone disease in an effort to prevent recurrent stone formation by urine dilution, provided a urimho value of less than 3 can be maintained. PMID- 1507359 TI - Metabolic stone disease. PMID- 1507358 TI - Composition of urinary calculi related to urinary tract infection. AB - The composition of 3,084 urinary calculi was determined using an infrared spectrophotometer. Mixed calcium oxalate-calcium phosphate stones were most frequently implicated. Of the urinary calculi analyzed 199 were associated with urinary tract infection. Escherichia coli was most frequently isolated (43 strains) and urease-producing organisms, such as Proteus mirabilis, were cultured from 40 patients. The core culture of 20 staghorn calculi yielded 15 isolates from 14 stones. There were 13 identical species isolated from the urine and stone specimens of 13 patients (65%), including 7 strains of P. mirabilis. These results suggest that cultures of urine specimens of urolithiasis patients, especially those with staghorn calculi, may help to elucidate the bacteriology of the stones. PMID- 1507360 TI - A piece of my mind. AIDS care curriculum. PMID- 1507361 TI - Physicians at AMA Amsterdam news seminar offer panoramic view of their varied roles in pandemic. PMID- 1507362 TI - Costs of HIV/AIDS rise, care disparities increase. PMID- 1507363 TI - From the National Institutes of Health. PMID- 1507364 TI - From the Centers for Disease Control. Testing for HIV in the public and private sectors--Oregon, 1988-1991. PMID- 1507365 TI - From the Centers for Disease Control. HIV exposure during nuclear medicine procedures. PMID- 1507366 TI - Consumer choices and the American health care system. PMID- 1507367 TI - Consumer choices and the American health care system. PMID- 1507368 TI - Consumer choices and the American health care system. PMID- 1507369 TI - Rapid classification of positive blood cultures. PMID- 1507370 TI - Priorities in Oregon. PMID- 1507371 TI - Intranasal cyanocobalamin. PMID- 1507372 TI - Removal of gastrostomy tubes. PMID- 1507373 TI - Reversing the natural decline in human fertility. An extended clinical trial of oocyte donation to women of advanced reproductive age. AB - OBJECTIVE: To evaluate the effect of age on pregnancy success rates in functionally agonadal women undergoing oocyte donation. DESIGN: A prospective study of 100 consecutive patients using oocyte donation for the treatment of infertility. PATIENTS: Women aged 40 years and above requesting oocyte donation (N = 104) were required to undergo medical, reproductive, and psychological screening. Suitable candidates (n = 65) were matched with an oocyte donor whose cycle was synchronized with that of the potential recipient, prior to the donor's undertaking ovarian hyperstimulation and transvaginal ultrasound-directed follicle aspiration. Outcomes were compared with those of two groups undergoing therapy at the same time: (1) women below 40 years of age undergoing oocyte donation for premature ovarian failure (n = 35) and (2) women 40 years of age and above undergoing standard in vitro fertilization and embryo transfer using their own oocytes (n = 57). MAIN OUTCOME MEASURES: Embryo implantation and pregnancy rates. SETTING: The in vitro fertilization program of the University of Southern California and the California Medical Center, Los Angeles. RESULTS: Improved outcomes were observed with regard to fertilization rates in vitro, number of embryos transferred, embryo implantation rate, clinical pregnancy rates, and ongoing or successfully completed pregnancy rates when women undergoing oocyte donation regardless of age were compared with women 40 years of age and above using their own oocytes. No age-related decline in fertility was demonstrable when oocyte donation was used, with a mean age of 44.3 +/- 3.1 years for those successfully conceiving (range, 40 to 52 years). Perinatal outcomes (n = 27) were generally uncomplicated, with a mean gestational age at delivery of 38.4 +/- 2.1 weeks (range, 34 to 42 weeks), although multiple births occurred in 24.1% of cases. CONCLUSIONS: The age-related decline in female fertility may be reversed in couples electing to use donated oocytes from a younger woman, and women of advanced reproductive age may conceive, carry, and give birth to infants with success rates similar to those of their younger counterparts using assisted reproductive methods. PMID- 1507374 TI - Hospital outbreak of multidrug-resistant Mycobacterium tuberculosis infections. Factors in transmission to staff and HIV-infected patients. AB - OBJECTIVE: To describe transmission of multidrug-resistant (MDR) Mycobacterium tuberculosis infection among patients and health care workers (HCWs) in a ward and clinic for human immunodeficiency virus (HIV)-infected patients in a hospital, four studies were conducted. METHODS: Case patients and control patients were persons who had been treated in the HIV ward or clinic, whose clinical course was consistent with tuberculosis and who had at least one positive culture for M tuberculosis between January 1, 1988, and January 31, 1990, resistant to at least isoniazid and rifampin (case patients), or whose isolates were susceptible to all drugs tested (control patients). In the first study, case patients and control patients were compared to identify risk factors for MDR tuberculosis. In the second study, inpatient and outpatient days of MDR tuberculosis case patients were compared to determine whether acid-fast bacillus (AFB) smear-positivity or aerosolized pentamidine use was associated with higher numbers of subsequent MDR tuberculosis cases among exposed patients. In the third study, restriction fragment length polymorphism analysis was performed on available MDR and sensitive M tuberculosis isolates. In the fourth study, skin test conversion rates among HCWs in the HIV ward and clinic were compared with those of HCWs in another ward, and the strength of the associations between skin test conversions among HCWs on the HIV ward and the number of person-days that AFB smear-positive case patients and control patients were on this ward was estimated. RESULTS: Case patients were more likely than control patients to have been exposed on the HIV ward or clinic to an AFB smear-positive case patient (P less than .001). Inpatient and outpatient days of MDR tuberculosis case patients were associated with more subsequent cases of MDR tuberculosis if exposing case patients were smear-positive or if they received aerosolized pentamidine (P less than or equal to .01). Of 13 MDR isolates, all had one of two restriction fragment length polymorphism patterns; 10 sensitive isolates had restriction fragment length polymorphism patterns that were different from each other. The HCW skin test conversion rate was higher on the HIV ward and clinic than on the comparison ward (P less than .01). The risk of occupational acquisition of infection increased in direct proportion to the number of person-days that AFB smear-positive case patients were on the HIV ward (r = .75; P = .005), but did not increase in proportion to the number of person-days that AFB smear-positive control patients were there (r = -.36; P = NS). After isolation measures for AFB smear-positive tuberculosis patients were improved, MDR tuberculosis cases decreased to seven of 214 tuberculosis patients. CONCLUSIONS: Nosocomial transmission of MDR M tuberculosis infection to patients and HCWs occurred on the HIV ward and clinic. Infectiousness of MDR tuberculosis case patients was associated with AFB sputum-smear positivity. Case patients with MDR tuberculosis created a greater risk of skin test conversion for HCWs on the HIV ward than drug susceptible control patients. PMID- 1507375 TI - Aspirin effects on mortality and morbidity in patients with diabetes mellitus. Early Treatment Diabetic Retinopathy Study report 14. ETDRS Investigators. AB - OBJECTIVES: This report presents information on the effects of aspirin on mortality, the occurrence of cardiovascular events, and the incidence of kidney disease in the patients enrolled in the Early Treatment Diabetic Retinopathy Study (ETDRS). STUDY DESIGN: This multicenter, randomized clinical trial of aspirin vs placebo was sponsored by the National Eye Institute. PATIENTS: Patients (N = 3711) were enrolled in 22 clinical centers between April 1980 and July 1985. Men and women between the ages of 18 and 70 years with a clinical diagnosis of diabetes mellitus were eligible. Approximately 30% of all patients were considered to have type I diabetes mellitus, 31% type II, and in 39% type I or II could not be determined definitely. INTERVENTION: Patients were randomly assigned to aspirin or placebo (two 325-mg tablets once per day). MAIN OUTCOME MEASURES: Mortality from all causes was specified as the primary outcome measure for assessing the systemic effects of aspirin. Other outcome variables included cause-specific mortality and cardiovascular events. RESULTS: The estimate of relative risk for total mortality for aspirin-treated patients compared with placebo-treated patients for the entire study period was 0.91 (99% confidence interval, 0.75 to 1.11). Larger differences were noted for the occurrence of fatal and nonfatal myocardial infarction; the estimate of relative risk was 0.83 for the entire follow-up period (99% confidence interval, 0.66 to 1.04). CONCLUSIONS: The effects of aspirin on any of the cardiovascular events considered in the ETDRS were not substantially different from the effects observed in other studies that included mainly nondiabetic persons. Furthermore, there was no evidence of harmful effects of aspirin. Aspirin has been recommended previously for persons at risk for cardiovascular disease. The ETDRS results support application of this recommendation to those persons with diabetes at increased risk of cardiovascular disease. PMID- 1507377 TI - Prescription drug diversion control and medical practice. AB - Concern about the role of prescription drug diversion in drug abuse has led to demands for more stringent regulation and for better ways to detect prescription drug diversion. Advances in technology now allow point-of-sale computer systems to report prescriptions filled by pharmacies to state agencies rapidly and possibly more economically. However, the advantages of more comprehensive control systems must be balanced against their possible effects on medical practice and patient care. Our limited knowledge about prescription drug diversion and the impact of diversion control systems on medical practice is summarized. Needed research is outlined together with the components of a diversion control program that balances reducing drug diversion with minimizing adverse effects on medical practice and patient care. We stress the need for broadly defined practice parameters and peer review by medical experts thoroughly familiar with the complexities of medical practice. PMID- 1507376 TI - Computer-based interview for screening blood donors for risk of HIV transmission. AB - OBJECTIVE: To test the ability of a computer-based interview to detect factors related to the risk of the human immunodeficiency virus (HIV) among potential blood donors and to determine donor reactions to the use of the interview. DESIGN: A comparison of the rate of detection of HIV-related factors elicited by a computer interview with that obtained by standard American Red Cross procedures for assessment of donor suitability, including a randomized crossover trial in which the order of the two methods was reversed. Information obtained by the computer was not available to influence the use of blood components for transfusion. SETTING: The computer interview was administered to donors at an American Red Cross blood donor center and at a mobile blood drive at a hospital. SUBJECTS: Consecutive sample of 294 male and female blood donors 18 to 75 years of age. MAIN OUTCOME MEASURES: Subjects' responses to the computer-based interview as well as responses to the standard Red Cross written questionnaires and face-to-face interviews were used for donor assessment. RESULTS: The interview took an average of 8 minutes to complete. From among 272 donors who provided complete data, the computer identified 12 donors who reported either behaviors associated with a risk of HIV acquisition or symptoms compatible with the acquired immunodeficiency syndrome; none of these donors had been so identified either by routine written questionnaires or by face-to-face interviews used to screen potential blood donors. Only one of the 12 identified donors used the confidential unit exclusion procedure to prevent use of his donated unit. The rate of elicitation of HIV-related factors by the computer interview was 12 (4.4%) of 272 (95% confidence interval [CI], 2.3% to 7.6%), compared with two (0.13%) of 1536 (95% confidence upper bound, 0.28%) using the standard Red Cross procedure (P less than .0001). Tests for antibodies to HIV were negative in blood samples from all of the 272 subjects studied. The subjects enjoyed the computer interview and judged it to be more private than the standard donor assessment method. They also predicted that donors would be more honest with the computer interview than with a human interviewer. CONCLUSIONS: Computer-based screening elicits more HIV-related factors in the health histories of blood donors than do the standard questionnaire and interviewing methods currently in use. Computer based screening is also acceptable to blood donors. PMID- 1507378 TI - Use of a novel technique of cutaneous lavage for diagnosis of Lyme disease associated with erythema migrans. AB - OBJECTIVE: Determining the microbial cause of cellulitis is often difficult. In this study, a novel two-needle lavage technique was used to culture Borrelia burgdorferi from the skin of suspected erythema migrans lesions. DESIGN: The yield of lavage cultures for B burgdorferi was compared with that of a 2-mm skin biopsy sample. SETTING: A Lyme disease diagnostic center located in an area in which Lyme disease is epidemic. PATIENTS: Forty-five patients with suspected erythema migrans who had not been treated with antimicrobial agents. INTERVENTION: Cutaneous lavage of the advancing edge of a suspected primary erythema migrans lesion was done for all 45 participants, 33 of whom also had a skin biopsy of the same lesion at an identical (14) or an adjacent (19) site. MAIN OUTCOME MEASURES: Growth of B burgdorferi in in vitro culture. RESULTS: Lavage fluid cultures grew B burgdorferi in 13 (29%) of the 45 cases (95% confidence interval [CI], 16% to 44%). Among the 33 cases in which both lavage and skin biopsy cultures were done, the yield of lavage culture was less than that of biopsy culture (P less than .09, 12/33 vs 20/33). If contaminated cultures are excluded, this difference is significant (P less than .05, 12/30 vs 20/27). CONCLUSION: Cutaneous lavage is a new diagnostic technique for recovery of B burgdorferi from erythema migrans lesions that has potential applicability to other types of cutaneous infections. PMID- 1507379 TI - NIH Consensus conference. Diagnosis and treatment of early melanoma. PMID- 1507380 TI - The new frontier of reproductive age. PMID- 1507381 TI - Assessing clinical instability at discharge. The clinician's responsibility. PMID- 1507382 TI - Uwe Reinhardt, PhD--the economist as health evangelist. PMID- 1507383 TI - Cutaneous tuberculosis. PMID- 1507384 TI - Sucralfate. PMID- 1507385 TI - Role of thymectomy in myasthenia gravis. AB - Thirteen patients with myasthenia gravis underwent total thymectomy between January, 1988 and December, 1991. The duration of symptoms prior to surgery varied from 2 months to 20 years. In a follow-up ranging from 2 months to 4 years, 11 patients showed a significant improvement with either complete discontinuation of medication or a marked reduction in doses. One patient with a small benign thymoma showed some improvement but subsequently required stepping up of anticholinesterase medication and addition of steroids and immunosuppressants; another patient with atrophic thymic tissue had complete remission after thymectomy but developed myasthenic symptoms six months later requiring medication again. Thymectomy is recommended for all patients with generalised myasthenia gravis with or without thymoma regardless of the duration of disease unless the patient is a very high risk candidate for surgery. It is not recommended for isolated ocular myasthenia gravis. PMID- 1507386 TI - Cholecystectomy in acute cholecystitis. AB - Of 130 patients admitted with acute cholecystitis, 100 were selected for a prospective study comparing the risks and benefits of early cholecystectomy versus initial conservative management followed by elective surgery. Comparative evaluation was carried out regarding operative difficulties and mishaps, postoperative complications, duration of hospitalization and compliance for surgery. Early cholecystectomy has advantage in terms of quick definitive treatment, completion of therapy in one hospital admission and salvage from serious complications of acute cholecystitis. Operative difficulties and mishaps and postoperative complications are comparable with delayed surgery. It obviates the danger of non-compliance by not reporting on the scheduled appointment. But it should be undertaken by an experienced surgeon and antibiotics should be administered prophylactically and following surgery to decrease the chances of septic complications. With these provisions it can be recommended as a treatment of choice for acute cholecystitis if the diagnosis can be established with confidence. PMID- 1507387 TI - Psychiatric morbidity among overseas students. AB - As immigration for higher education is becoming more common now a days, the adjustment of overseas students to the host country is receiving more attention. This paper describes the results of a study which examined the prevalence and pattern of psychological disturbances among overseas and British students studying at Edinburgh University. The practical implications of these findings and suggestions for future research are discussed. PMID- 1507388 TI - Prevalence of iron deficiency anaemia in children of the urban slums of Karachi. AB - A preliminary baseline survey was conducted to estimate the prevalence of anaemia in a group of 391 children aged 6-60 months, randomly selected from three urban slums of Karachi. Haemoglobin and the red cell indices including haematocrit, MCV, MCH, MCHC, RBC and red cell distribution width (RDW) were estimated for each of the selected children. Ferritin estimation was done on 354 (91%) children to assess the iron storage status. According to WHO criteria, the accepted cut-off point for anaemia screening in children is set at 11 gm/dl, 70 fl and 20 pg for haemoglobin, MCV and MCH respectively. Following these criteria, 118 (30%) children were classified as normals (Hg = greater than 11 gm/dl) and 273 (70%) as anaemic (Hg = less than 11 gm/dl). Of the 354 ferritin estimations, 225 (64%) children had ferritin levels lower than normal (less than 11 ng/ml) and 128 (36%) had ferritin levels within normal limit (11-120 ng/ml). From this group, a total of 61% (214/354) children were classified as microcytic hypochromic (MIH) and 11% (39/354) of which had normal ferritin levels suggesting the presence of thalassemia minor trait. The overall results obtained indicate that iron deficiency anaemia is highly prevalent among these children. PMID- 1507389 TI - IgM and IgG antibodies specific to rubella in child bearing women. AB - Three hundred fifty five pregnant women were tested for IgM and IgG type of antibodies by Enzyme Immuno Assay (EIA). Sero-positivity for IgM and IgG antibodies were 13% and 29% respectively. Of 212 pregnant women with abortion, 39 (18%) and 80 (38%) were sero-positive and of 143 pregnant women with normal reproductive performance, 7 (5%) and 23 (16%) were positive for IgM and IgG respectively. Premarital screening and vaccination of Sero-negative girls is recommended to reduce morbidity and mortality related to rubella virus. PMID- 1507390 TI - Wrist ganglion. PMID- 1507391 TI - Relapse in heroin addiction--a brief report. PMID- 1507392 TI - Ovarian ectopic pregnancy and misplaced intrauterine device. PMID- 1507393 TI - [Bacteriological evaluations of combination therapies with minocycline and beta lactams for methicillin-resistant Staphylococcus aureus. I. Cefotiam plus minocycline]. AB - Since methicillin-resistant Staphylococcus aureus (MRSA) is resistant to multiple antibiotics, only a limited number of antibacterial agents shows efficacy against this bacteria. Therefore, combination therapy is often attempted for MRSA infections. Most of the MRSA strains recently isolated, however, have been found to show very high resistance, and some of the antibiotics which had previously been effective have been failing to produce good responses in increasing numbers of patients. Thus, the drugs used for combination therapy in MRSA infections need to be reevaluated. We assessed the bacteriological efficacy of cefotiam (CTM) plus minocycline (MINO) therapy against MRSA in an in vitro system (CTM shows relatively strong antibacterial activities against MRSA with moderate resistance, and MINO shows strong antibacterial activities against highly resistant MRSA. 1. Against MINO-susceptible MRSA strains, CTM + MINO demonstrated potent antibacterial activities at MINO concentrations of MIC or sub-MIC levels, irrespective of the MIC of CTM against MRSA strains being tested. 2. Against MINO resistant MRSA strains (strains for which MICs of MINO exceeded the upper limit of the clinically expected plasma MINO level), CTM + MINO showed no significant antibacterial activity. These results suggested that the effect of this combination was dependent on the antibacterial activity of MINO. Therefore, the usefulness of this combination in patients with MRSA infections can be predicted based on susceptibilities of involved strains to MINO. 3. The potent antibacterial effect of this combination against MINO-susceptible MRSA strains was considered to be the result of damage to the cellular membrane by MINO and the subsequent antibiotic effect of CTM.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1507394 TI - [Bacteriological evaluations of combination therapies with minocycline and beta lactams for methicillin-resistant Staphylococcus aureus. II. cefuzonam plus minocycline]. AB - We performed an in vitro assessment of the antibacterial activity of therapy with cefuzonam (CZON) plus minocycline (MINO) against methicillin-resistant Staphylococcus aures (MRSA) infections. 1. Studies using MINO-susceptible and MINO-resistant MRSA strains suggested that the antibacterial activity of CZON + MINO was dependent on the antibiotic action of MINO, similarly to the case with cefotiam (CTM) + MINO. 2. The antibacterial activity (including the FIC index) of this combination was slightly inferior to that of CTM + MINO. However, the time course of antibacterial efficacy of CZON + MINO in MRSA pretreated with MINO was comparable to that of CTM + MINO. 3. CZON + MINO appeared to be a very useful combination in patients with mixed infections due to MRSA and Gram-negative bacteria. PMID- 1507395 TI - [Cefepime (diHCl/L-arginine blend): intravenous continuous infusion and/or single dose subcutaneous toxicity study in rats and dogs]. AB - To investigate single dose toxicity of cefepime (CFPM diHCl/L-arginine blend), the test drug was administered to rats [Crj: CD (SD)] of both sexes at dose levels of 500, 1,000 and 2,000 mg/kg using intravenous continuous infusion or subcutaneous injection, and to male beagle dogs at 1,000 and 2,000 mg/kg using intravenous continuous infusion. As the control, two additional groups of each animals were given either saline or L-arginine alone which was used in the test formulation to adjust pH values of CFPM diHCl solutions. The obtained results are summarized as follows: 1. Rats dosed with 2,000 mg/kg CFPM through intravenous continuous infusion showed slightly decreased spontaneous physical activity. One male rat dosed with L-arginine alone via continuous infusion also showed slightly decreased activity. Slight to severe inflammatory reactions at injection sites including sloughing of the tail were prominent at doses of 1,000 or 2,000 mg/kg of CFPM, or L-arginine alone. Average body weights of rats in the test groups of either sex were comparable to the controls in all of the dose groups of the same sex during the 14-day test period. 2. Rats receiving 2,000 mg/kg CFPM in single subcutaneous injection showed slightly diminished activities. Slight to moderate reactions occurred around the injection site (viz., hardening, depilation, scab formation and necrosis) in rats injected any of the 3 doses of CFPM. Though body weight gains were slightly retarded in male rats receiving 2,000 mg/kg CFPM during the last half of the observation period, such weight gain retardation was not observed in rats of other dose groups.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1507396 TI - [Cefepime (BMY-28142 diHCl/L-arginine blend): one-month repeated dose subcutaneous toxicity study in rats]. AB - In order to investigate the toxicity of cefepime (CFPM, BMY-28142 diHCl/L arginine blend upon repeated subcutaneous dosing), the test article was administered to Crj:CD(SD) rats of both sexes at daily dose levels of 150 (low dose), 500 (intermediate dose) and 1,500 (high dose) mg/kg/day by subcutaneous route for 28 days. Two additional groups of rats were given either saline (negative control) or L-arginine (vehicle control). Doses were equally divided and administered twice each day with an interval of approximately 5 hours between the 2 doses of a same day. A half of rats in negative control and high dose groups were retained for examination during one-month recovery period. The results obtained are summarized as follows: 1. Upon general observations, it was found that drug-related changes were restricted to the injection sites. Depilation and scab-formation of the injection sites were noted in high dose rats of both sexes and intermediate dose females. No deaths occurred during the study. 2. Slightly depressed body weight gains were observed for high dose males during the latter part of the dosing period. 3. Slightly lower food consumptions were noted for intermediate and high dose males at Week 1. 4. Slightly higher water consumptions were generally detected for high dose rats during the dosing period. 5. Hematological examinations revealed that a slight decrease in the average value of relative lymphocyte counts and a slight increase in the average value of relative segmented neutrophil counts were evident for high dose males. These findings might be attributable to the inflammatory reactions at the injection sites.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1507397 TI - [Reproductive and developmental toxicity studies on cefepime dihydrochloride administered subcutaneously to rats during the premating, gestation and lactation periods]. AB - Cefepime dihydrochloride (CFPM) was administered subcutaneously daily at doses of 0, 150, 500 and 1,000 mg/kg for 63 days prior to mating and during mating to male Crj: CD (SD) rats and for 14 days prior to mating and during mating, as well as periods of gestation and lactation to female SD rats. Saline and L-arginine hydrochloride (L-arginine) were used as control articles. Daily doses of test and control articles were equally divided and administered twice a day (b.i.d.). The results obtained are summarized as follows: 1. Soft stool was observed for both male and female F0 rats at CFPM 1,000 mg/kg at the first week of administration period. Further, depilation of injection sites was found in 7 males and 12 females at the same dose level. 2. Body weight gains were suppressed in male F0 rats from Day 28 to 63 of administration period at CFPM 1,000 mg/kg. Moreover, food consumption was reduced in F0 female rats during the first week of administration period at all dose levels of CFPM. 3. CFPM failed to affect the reproductive performance in both male and female F0 rats. 4. Kidney weights were increased in both male and female F0 rats and adrenal weights were augmented in male F0 rats at CFPM 1,000 mg/kg. On the other hand, cecal enlargement were observed for F0 dams treated with CFPM. However, these changes were not considered to be unique to this drug, because they have been described with most antibiotics in this species and appears to be results of modifications in gut flora. 5. Prenatal developments in F1 fetuses were not affected by CFPM. 6. CFPM failed to affect delivery status of F0 dams or survival and lactation indices in F1 pups. 7. CFPM did not affect postnatal differentiations, developmental behaviors, learning ability and memory, spontaneous motor activity or emotionality in F1 rats. 8. Body weight gains and food consumption in both male and female F1 rats were not affected by CFPM. 9. CFPM did not alter the organ weights in both male and female F1 rats. 10. There were no significant differences between drug treated animals and controls regarding the reproductive performance and delivery status of F1 rats. 11. Influences on survival indices, body weights and organ weights were not apparently observed for F2 pups even at CFPM 1,000 mg/kg. Based on the reproductive and developmental indices, the no effect dose level of CFPM under the present experimental condition was estimated to be 1,000 mg/kg/day against dams (F0) and their offspring (F1). PMID- 1507398 TI - [General pharmacology of cefepime]. AB - General pharmacological properties of cefepime (CFPM), a new injectable semisynthetic cephalosporin and its metabolite N-methylpyrrolidine-N-oxide (NMP-N oxide) were studied in laboratory animals. The results obtained are summarized as follows: 1. CFPM reduced spontaneous locomotor activity but potentiate the anesthesia at the highest dose in mice. Furthermore, significant hypothermia and analgesia were observed at the same dose in mice. No effects were found on the other CNS function in mice and rats or on EEG activities in rabbits. 2. Muscle relaxant activity was not observed in mice treated with CFPM even at the highest dose. 3. CFPM had no effect on the intestinal smooth muscle and did not show any antagonism against some smooth muscle contracting drugs. 4. The respiration, blood pressure, heart rate and ECG were affected by CFPM. Those changes, however, might have been principally caused by L-arginine blended with CFPM product. 5. No effect of CFPM on the intestinal movement or gastric secretion was found even at the highest dose of CFPM. 6. The pH neutralizer L-arginine caused alterations in the renal function and electrolyte metabolism but CFPM did not. 7. Whole blood clotting time tended to be lengthened by CFPM at the highest concentration but this effect seemed to have been caused by L-arginine. Other parameters of the coagulation system or red blood cell resistance were not affected by CFPM. 8. NMP N-oxide, a metabolite of CFPM, had almost no effect on any of the tested parameters except for its slight effect on the circulatory system. These findings indicate that CFPM has scarcely any pharmacological properties which might be leading to severe adverse reactions in clinical use. PMID- 1507399 TI - [Clinical efficacy of ceftriaxone when administered once daily for respiratory tract infections in patients with advanced ages]. AB - Ceftriaxone (CTRX), a new third generation cephalosporin, was investigated upon once daily administration for its clinical efficacy and safety on respiratory tract infections in patients with advanced ages. The results are summarized as follows: 1. Clinical responses to CTRX of 48 cases of advanced age patients with respiratory tract infections were good with an efficacy rate of 89.6%. 2. Adverse reactions to CTRX were mainly exanthema in 7 cases (14.6%). 3. Serum levels of CTRX were determined in 4 cases after intravenous drip infusion of 2 g CTRX. Serum levels were analyzed by one-compartment model. There was no evidence of accumulation of CTRX in the patients with advanced ages. PMID- 1507400 TI - [Therapeutic effects of meropenem against severe infections in patients with hematopoietic disorders. Hanshin Study Group of Hematopoietic Disorders and Infection]. AB - The efficacy and the safety of meropenem (MEPM), a newly developed carbapenem antibiotic, were investigated in 150 patients with severe infections complicated with hematopoietic disorders. 1. Clinical responses in 132 patients who were evaluable for effectiveness were excellent in 33 patients, good in 45, fair in 10 and poor in 44, with an efficacy rate of 59.1%. 2. The efficacy rate in patients who had previously been treated with the other antibiotics was 51.2%, while that in patients who had not been thus treated was 62.9%. 3. The efficacy rate in patients whose neutrophil counts increased during the therapy with MEPM was higher than that in patients whose neutrophil counts did not increase. The efficacy rate in patients whose neutrophil counts during the therapy were below 100/mm3 was 48.1%. 4. Out of 150 cases, side effects were observed in 4 patients, 3 with eruption and 1 with jaundice. Abnormalities in laboratory test results on liver functions were noted in 8 patients. These results indicate that MEPM is an effective and safe antibiotic for the treatment of severe infections in patients with hematopoietic disorders. PMID- 1507401 TI - [Pharmacokinetic and clinical studies with meropenem in the pediatric field. Pediatric Study Group of Meropenem]. AB - Pharmacokinetic and clinical evaluations in pediatrics were made on meropenem (SM 7338, MEPM), a new parenteral dehydropeptidase-1 stable carbapenem used without any inhibitors, at 33 medical institutions. The results are summarized as follows. 1. Pharmacokinetic studies. MEPM at a dose of 10, 20, or 40 mg/kg was administered to 53 children by 30-minute drip infusion. Peak plasma concentrations (Cmax's) and plasma half-lives (T1/2's) of these doses were 28.5, 47.2 and 130.0 micrograms/ml, and 0.80, 0.93 and 0.94 hours, respectively. A clear dose response was observed in Cmax's and T1/2 values were quite similar to those observed in adults. In the first 6 hours after administration, 54.4 to 68.1% of the administered drug was recovered in urine. The cerebrospinal fluid (CSF) levels of MEPM in patients with purulent meningitis were 0.13 microgram/ml at a dose of 6 mg/kg, and 0.64 to 4.22 micrograms/ml at a dose of 29 to 44 mg/kg within day 4 of onset. The penetration rate of MEPM showed an intermediate value among those for other cephalosporin antibiotics. 2. Clinical study. Clinical efficacies of MEPM were evaluated in 389 cases. The most common doses used were 10 to 20 mg/kg/once, 2 to 3 times a day. The maximum dose was 173 mg/kg/day q.i.d. MEPM gave "excellent" or "good" responses in 242 (97.6%) out of 248 cases in which causative organisms were documented and in 134 (95.0%) out of 141 cases in which causative organisms were not identified. Clinical efficacy rates were 100% in 11 patients with purulent meningitis, 85.7% in 7 with septicemia, 98.8% in 173 with pneumonia, and 100% in 65 with UTI. Bacteriologically, 260 strains (96.7%) out of 269 strains were eradicated by MEPM treatment. Eradication rates were 89.2% for Staphylococcus aureus (37 strains) and 100% for Streptococcus pneumoniae (35 strains). The overall eradication rate for Gram-positive bacteria was 94.6%. Among Gram-negative bacteria, 98.3% out of 172 strains were eradicated. The eradication rate of Haemophilus influenzae (73 strains) was 98.6% and Pseudomonas aeruginosa (11 strains) was 90.9%, and all of Branhamella catarrhalis (15 strains), Escherichia coli (42 strains), and Klebsiella pneumoniae (6 strains) were eradicated. Out of 84 cases for which previous antibiotic therapies of 3 days or longer were not successful, MEPM gave "excellent" or "good" responses in 77 cases (91.7%) and excellent bacteriological responses (95.7%).(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1507402 TI - [Clinical and pharmacokinetic evaluation of meropenem and its effect on fecal flora in children]. AB - Forty-five children were treated with meropenem (MEPM) and the clinical efficacy and side effects were evaluated. The ages of the patients ranged from 1 month to 9 years and their body weights from 5.2 to 25 kg. Doses given were 17.2-45.5 mg/kg every 6 to 8 hours for 2 to 24.5 days. Those patients who responded to the MEPM treatment included 15 children with pneumonia, 7 with pharyngitis, 3 with cervical lymphadenitis, 3 with cellulitis, 10 with urinary tract infections and 4 with other infections. Among 42 children, the results were excellent in 29, good in 12 and fair in 1. The drug was well tolerated, although slightly elevated serum concentrations of transaminases occurred in 5 patients, eosinophilia in 2 patients, and neutropenia in 1 patient among 45 patients examined. The pharmacokinetic studies on MEPM were done in 6 patients. Their ages ranged from 2 to 9 years and body weights from 14.5 to 23.2 kg. In 4 patients, plasma concentrations at the end of 30 minutes drip infusion of 20 mg/kg were 29.28 +/- 10.29 micrograms/ml and those 3 hours later were 0.49 +/- 0.26 micrograms/ml. Serum elimination half-lives of the drug were 0.66 +/- 0.12 hours in these patients. Excretion rates of this drug into urine in the first 6 hours after initiation of drug administration were 53 and 40% in 2 of these patients. In 2 patients with 35 and 44 mg/kg of drug administration, plasma concentrations were higher than those given 20 mg/kg of the drug.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1507403 TI - [Clinical pharmacology and efficacy of meropenem]. AB - We studied a newly developed carbapenem, meropenem (MEPM), and obtained the following results. 1. Pharmacokinetics of MEPM in pediatrics was examined in 3 patients. MEPM was injected intravenously at a dose of 16-22 mg/kg by drip infusion for 30 minutes, and its concentrations in serum and urine were determined using bioassay. The average peak value of serum levels of MEPM was 38.4 micrograms/ml and T1/2 beta of MEPM was 1.26 hours. The urinary recovery rate for the first 6 hours after administration was 65.6%. 2. Clinical evaluations of MEPM in pediatrics were done in 14 patients with ages ranging, 1 month to 14 years, with various bacterial infections. Excellent or good clinical responses were observed in all patients, and bacteriological eradication were obtained in 7 out of 8 cases. No serious side effects were observed in any cases, but 2 showed mild and transient GOT, GPT elevations. PMID- 1507404 TI - [Clinical evaluation of meropenem in children]. AB - Meropenem (MEPM) was evaluated for its efficacy and safety. The following results were obtained. MEPM was given to 12 patients with infections: 5 with pneumonia, 1 with bacterial meningitis, 2 with pharyngitis, 4 with skin and soft tissue infections. Therapeutic responses were "excellent" in 5, "good" in 4 and "fair" in 3, with an efficacy rate of 75%. Adverse reactions were not noted. No abnormalities were shown in laboratory data. It has been concluded that MEPM is a useful drug for the treatment of bacterial infections in children. PMID- 1507405 TI - [Clinical evaluation of meropenem in the pediatric field]. AB - We studied the clinical efficacy of meropenem (SM-7338, MEPM), a new parenteral carbapenem beta-lactam antibiotic, in pediatric field. Thirteen patients with 2 months to 8 years and 8 months of ages, with acute infectious diseases were administered with doses at 39.3 to 76.7 mg/kg/day of MEPM intravenously. The diagnoses consisted of 7 respiratory tract infections, 1 sepsis, 2 orbital cellulitis, 1 parotid abscess, 1 lymphadenitis and 1 pyoderma. The clinical efficacy rate was 84.6% (11/13), and the bacteriological eradication rate was 71.4% (5/7). Clinical laboratory examinations revealed 1 patient with eosinophilia and another with anemia. No other side effects attributable to this drug were observed. It appears that MEPM is a useful antibiotic for moderate to severe acute bacterial infections in children. PMID- 1507406 TI - [Bacteriological and clinical studies on meropenem in the pediatric field]. AB - Bacteriological and clinical studies have been performed on meropenem (MEPM, SM 7338), a newly developed carbapenem antibiotic, in the pediatric field. 1. Antibacterial activities of MEPM against 24 clinical isolates were determined. MEPM showed excellent activity against Gram-positive bacteria including Staphylococcus aureus and Gram-negative bacteria, especially Escherichia coli and Branhamella catarrhalis. Against Haemophilus influenzae, MEPM had a higher activity than imipenem and flomoxef, but had a lower activity than piperacillin and cefoperazone. 2. Clinical efficacies of MEPM were evaluated in 32 cases with bacterial infections. A poor efficacy was observed in 1 patient with phlegmon but excellent or good efficacies were obtained in other 31 patients with tonsillitis (1), pneumonia (17), UTI (12), or SSSS (1). The overall efficacy rate was 96.9%. All strains except 1 of S. aureus were eradicated by the administration of MEPM, and a high eradication rate of 95.8% (23 out of 24 strains) was obtained. 3. No side effects were observed in 35 evaluated cases. As abnormal laboratory test results, elevated GOT, elevated GPT, eosinophilia and neutropenia were noted in 4, 4, 4 and 2 patients, respectively. 4. Influences on blood coagulation parameters were studied. PIVKA II was elevated upon administration of MEPM in some cases, but no changes in ATT, TT, HPT or Fbg were observed during the treatment. Based on the above results, it has been concluded that MEPM is a safe and effective drug to use in the treatment of pediatric infections. The usual recommended dosage and administration should be 10 to 20 mg/kg of MEPM at a time, using intravenous drip infusion, 3 times a day. PMID- 1507407 TI - [Aplastic anemia]. PMID- 1507408 TI - [Refractory aplastic anemia: the current status and future prospect]. PMID- 1507409 TI - [Treatment of idiopathic thrombocytopenic purpura]. PMID- 1507410 TI - [Autoimmune hemolytic anemia]. PMID- 1507411 TI - [Therapy of paroxysmal nocturnal hemoglobinuria]. PMID- 1507412 TI - [Purging of leukemic cells using alkyllysophospholipid]. PMID- 1507413 TI - [Detection of MRD using BCR/ABL and immunoglobulin gene]. PMID- 1507414 TI - [Autologous bone marrow transplantation in malignant hematologic tumors--the current status and future problems involving children]. PMID- 1507415 TI - [Autologous bone marrow transplantation in malignant hematogenous tumor of adults -the current status and problems in Japan]. PMID- 1507416 TI - [Report of IAEA International Chernobyl Project 1990-1991]. PMID- 1507417 TI - [Favorable prognoses in 24 adult patients with acute leukemia, surviving over five years since 1985]. AB - Since 1985 we have experienced 24 leukemia cases with long-term survival, who were treated with one of three types of postremission therapy. Of them, 20 patients were physically fit for ordinary work and returned to their work as workers or housewives during long-term follow-up period. Two housewives gave birth. We have devised three types of postremission therapy; 1) multidrug combination therapy with gradually longer intermissions (January 1980-March 1983); 2) controlled randomized clinical trial by the Japanese Foundation for the Multidisciplinary Treatment of Cancer, April 1983-March 1985-March 1988). In a group who underwent multidrug combination therapy without prednisolone, 12 of 20 patients who achieved complete remission have shown continued complete remission, as of November 1991, including seven 5-year survivors. These results indicate that improvement of postremission therapy makes it possible for adult patients with acute leukemia to survive 5 years or longer. PMID- 1507418 TI - [Philadelphia chromosome (Ph1) positive acute myelomonocytic leukemia with esophageal cancer: a case report]. AB - A 62-year old male was admitted to our hospital because of fever and dysphagia on November 14, 1987. The peripheral leukocyte count was 174,400/microliters with 93% blasts and bone marrow aspiration showed that 90.4% of nucleated cells were blasts positive for both myeloperoxidase and alpha-naphthylbutyrate esterase. Chromosome analysis revealed a karyotype of 45XY, 9q+, 16q+, -20 and 22q-. Esophageal X-ray and endoscopy showed abnormalities. Esophageal biopsy revealed squamous cell carcinoma. He was diagnosed as having Ph1 positive acute myelomonocytic leukemia (AMMoL, M4) and esophageal cancer. He was treated with BHAC-DMP and intermediate-dose ara-C therapy for leukemia and a complete remission was obtained by March 25, 1988. As treatment for esophageal cancer, radiation therapy (total 4,200 cGy) was given and followed by chemotherapy with CDDP and 5-FU. However he died on April 8, 1988. Autopsy findings showed disseminated invasion of esophageal cancer. Ph1 positive AMMoL associated with esophageal cancer is extremely rare. PMID- 1507419 TI - [Sick sinus syndrome in a patient with myeloma-associated amyloidosis]. AB - A 62-year-old woman was admitted with general malaise and anorexia in September, 1988. Multiple myeloma (IgA-lambda, Stage IIIb) was diagnosed, and amyloidosis was also diagnosed by abdominal fat aspiration biopsy. A partial remission was achieved by MEVP combination chemotherapy, and she was discharged in December, 1988. She was readmitted because of dizziness and palpitation in April, 1989. A diagnosis of sick sinus syndrome was made, and a VVI permanent pacemaker (PPM) was implanted. She was able to walk to our outpatient clinic for 10 months after the PPM implantation. However, right hemiplegia and aphasia were recognized on April 19, 1990. CT scans revealed low density in the areas of the left anterior and middle cerebral artery. The symptoms of congestive heart failure worsened progressively, and the patient, who had been confined to bed, died on March 5, 1991. She was the fifth myeloma-associated amyloidosis patient who received a PPM implantation. Her survival time was one year and ten months, and was the longest among a small number of reported cases with PPM implantation. PMID- 1507420 TI - [Three familial patients with chronic acquired pure red cell aplasia]. AB - It has not been reported that chronic acquired pure red cell aplasia (PRCA) occurs among family members. The authors report his at familial patients with chronic acquired PRCA, a 23-year-old male, a 54-old uncle and a 20-year-old male cousin. They had no complication sor thymoma, and hematological findings were compatible with typical chronic acquired PRCA. In the 23-year-old male, the autologous BFU-E number was suppressed by the addition of pretreatment serum, and in the his uncle, the autologous CFU-E number was suppressed by the addition of IgG fraction of plasma. In these cases, the development of PRCA was considered to be based on the autoimmune mechanism due to by the presence of serum antibodies. This suggests the possibility that genetically inherited susceptibility may also be an important factor causing chronic acquired PRCA. PMID- 1507421 TI - [Secondary sideroblastic anemia caused by long term administration of anti tuberculous agents including isoniazid]. AB - A 54 year-old man, who had been treated for several years with isoniazid, was transferred to our hospital because of intractable pulmonary tuberculosis. He was given several anti-tuberculous agents including INH, CS and/or PZA for a long period of time without improvement of the pulmonary tuberculosis. After 7 years' treatment with INH, hypochromic microcytic anemia developed. Parenteral administration of iron preparation failed to improve the anemia. The bone marrow findings revealed erythroid hyperplasia and a few erythroblasts showed megaloblastic change. The bone marrow iron staining revealed increased sideroblasts of which 88% were ringed-form. INH was then discontinued and pyridoxal phosphate was administered with rapid complete improvement of the anemia. INH is well known as a causative agent for acquired secondary sideroblastic anemia, however only one case of INH-induced sideroblastic anemia has been reported in Japan. This is the second reported Japanese case of INH induced secondary sideroblastic anemia, which appears to be a very rare condition because of genetically determined rapid acetylation of INH in Japanese. PMID- 1507422 TI - [Successful treatment of prolonged anemia after major ABO incompatible bone marrow transplantation for a case of myelodysplastic syndrome with recombinant erythropoietin]. AB - A delay in red cell recovery after ABO-incompatible bone marrow transplantation (BMT) is often observed. The authors experienced a case of prolonged anemia after a major ABO incompatible BMT for myelodysplastic syndrome which was successfully treated with recombinant human erythropoietin (Epo). Effects of Epo were confirmed by the recurrence of anemia after withdrawal of Epo as well as the rapid reincrease in reticulocytes on readministration. The patient received a dose of Epo which was similar to the amount used for renal anemia, however serum concentration of Epo after administration exceeded endogenous Epo levels. Epo may have a beneficial role in the treatment of prolonged anemia after BMT. PMID- 1507423 TI - [An epidemiological study of methicillin-resistant Staphylococcus aureus (MRSA) isolated from medical staffs, inpatients and hospital environments at our hospital]. AB - Methicillin-resistant Staphylococcus aureus (MRSA) is one of the most important microorganisms which is causative of the nosocomial infections. Recently the incidence of isolation of MRSA is increasing from year to year in Japan. Especially MRSA isolated from inpatients are much higher than from outpatients. Therefore we have done epidemiological studies about MRSA isolated from medical staffs, inpatients and hospital environments in our hospital. Thereafter we examined phage typing and coagulase typing of those MRSA. MRSA were isolated more frequently from anterior nares of inpatients in compare with doctors and nurses. MRSA were isolated more frequently from the environments of MRSA carriers. Coagulase type II and phage type N.T. (not typable) were dominant type of MRSA in our hospital (69% and 61%). Our studies have revealed that the isolation frequency of MRSA is very high in our hospital. It seems to suggest that inpatients who are carrying MRSA are spreading MRSA out hospital environments and medical staffs. PMID- 1507424 TI - [An attempt to control nosocomial methicillin-resistant Staphylococcus aureus (MRSA) infection]. AB - A strain of Methicillin-Resistant Staphylococcus aureus (MRSA) was first isolated in our hospital in March 1986. Since then, MRSA has become a difficult pathogen and a cause of sepsis, bacterial endocarditis, and pneumonia in 1988. Rigorous hospital-wide control measures have been planned. The major control measures, based on the various investigations reported, consist of the following three points; improvement of environmental control, reinforcement of handwashing practices during care and control usage of antibiotics. The frequency of isolation of MRSA among the S. aureus isolates was 43.3% in 1988 and this was further reduced to 31.7% in 1990. The total number of MRSA isolates from decubitus, bile, and blood samples have also declined. This decline resulted in a reduction of cases of severe MRSA infection. As yet, MRSA strain are still isolated on incubation. There may be a limit to complete control by measures in a single hospital. It is desired that regional measures and national consensus on nosocomial infection be established. PMID- 1507425 TI - [The structure and function of the mecA gene in methicillin-resistant Staphylococcus aureus]. AB - Penicillin binding protein (PBP) 2' is the most important mechanism of the resistance to beta-lactams in methicillin-resistant Staphylococcus aureus (MRSA). And the mecA gene is the coding gene of PBP2', and located in the SmaI fragment G of the chromosome map by Pattle P.A.,. A part of the structure of mecA is similar to that of the penicillinase gene. The resistance of MRSA to beta-lactams were influenced by the presence of penicillinase plasmid and the alternation of femA gene. PMID- 1507426 TI - [Characterization of femA gene product by penicillin-binding protein assay]. AB - To characterize the femA gene product by penicillin-binding protein (PBP) assay, cloned femA sequence was introduced into methicillin-sensitive femA mutant Staphylococcus aureus BB308 and into Escherichia coli JM109. Overproduced femA gene product was detected in the membrane fraction of the S. aureus and E. coli transformants by SDS-PAGE and Coomassie-blue staining, but no penicillin-binding activity was observed in the femA gene product. Both BB308 and its transformant produced PBP 2' and other PBPs, as much as clinically isolated methicillin resistant S. aureus strains. The degree of restoration of methicillin resistance varied depending on the introduced femA sequences derived from six different S. aureus strains. A hypothetical mechanism of femA to affect beta-lactam resistance in S. aureus is discussed. PMID- 1507427 TI - [The beta-lactamase activity in methicillin-resistant Staphylococcus aureus--a comparison of the beta-lactamase from a methicillin-resistant and from a methicillin-sensitive strain of Staphylococcus aureus]. AB - Strains of Methicillin-resistant Staphylococcus aureus (MRSA) are more frequently beta-lactamase-negative than those of Methicillin-susceptible S. aureus (MSSA). In the strains of MRSA, the beta-lactamase activity tends to be inversely related to the MIC's of Methicillin. Such a marked tendency has been observed in recent years. PMID- 1507428 TI - [Vancomycin and arbekacin, drugs of treatment for MRSA infections]. AB - In Japan, the Ministry of Health and Welfare has permitted recently that vancomycin is given parenterally. Therefore, this drug will be useful for the treatment for MRSA infections. Arbekacin, a newly developed aminoglycoside antibiotic, showed more active than vancomycin to MRSA in vitro. Therefore this drug will be also useful for the treatment for MRSA infections. Combined activity of arbekacin and vancomycin against 27 MRSA strains was evaluated by checkerboard technique. No synergistic effects were detected against these strains. Antagonistic effects were observed against 2 strains. "Vancomycin-arbekacin combined therapy" should be done, therefore, to restricted cases. PMID- 1507429 TI - [Effective single and combined chemotherapeutic regimens as regards to antibiotic resistance patterns of methicillin-resistant Staphylococcus aureus (MRSA) in Japan]. AB - The incidence of gentamicin-resistant MRSA (GMr-MRSA) has been gradually increasing since early 1980's in Japan. The GMr-MRSA mainly belongs to Group-I phage type and to Group-IV coagulase type. It is rather difficult to induce methicillin-resistance in the GMr-MRSA in the presence of beta-lactam antibiotics. Since late 1980's tobramycin-resistant MRSA (TOBr-MRSA) has been increasing rapidly in place of GMr-MRSA. The TOBr-MRSA mostly belongs to Group III phage type and Group II coagulase type. It rapidly acquires resistance to methicillin and becomes highly resistant to many other related antibiotics as evidenced by statistics in 1980's in Japan. A combination chemotherapy with imipenem/cilastatin and 1st or 2nd generation cephem, or minocycline plus cephem is considered to be effective for MRSA infections. However, a combination chemotherapy with arbekacin (ABK), or vancomycin (VCM) plus beta-lactam antibiotic is recommended especially for the treatment of respiratory tract infections. PMID- 1507430 TI - [MRSA respiratory tract infection]. AB - Sputum isolates of MRSA have been on the increase, recently. Preventive measures against MRSA nosocomial infections have become important in Japanese hospitals. Clinical study was performed on 29 patients from whom MRSA was isolated more than 10(7) cfu/ml using the quantitative sputum culture method. All had a history of admission, therefore nosocomial infections caused by MRSA could very often occur. MRSA was determined as a causative organism in 3 on the basis of symptoms, laboratory data, chest X-rays, and effect of antimicrobial agents. These three patients improved by a single or combined administration of minocycline, arbekacin and/or fosfomycin. In 15 patients, MRSA was frequently isolated, but was thought to be colonized. In 3 patients, MRSA was not isolated without administration of antimicrobial agents thereafter. It was supposed that most of MRSA isolates from sputum were not the causative organism of the respiratory tract infection. PMID- 1507431 TI - [Bacteremia due to methicillin-resistant Staphylococcus aureus (MRSA)]. AB - Bacteremia due to methicillin-resistant Staphylococcus aureus (MRSA) is most likely to occur in compromised patients with prolonged hospitalization who are receiving antibiotics, particularly beta-lactam ones. The clinical picture of MRSA bacteremia is almost the same as that of bacteremia due to methicillin sensitive S. aureus. There seems to be no significant difference in prognosis between the two types of staphylococcal bacteremia when patients in the same disease category are considered. Vancomycin is at present the only antibiotic for the treatment of MRSA bacteremia. It is therefore important to use the drug adequately so as to prevent its adverse effects and delay the appearance of resistant organisms. PMID- 1507432 TI - [Clinical spectrum of antibiotic associated enterocolitis due to methicillin resistant Staphylococcus aureus]. AB - Historically, various types of antibiotic-associated diarrhea have been recognized. In the 1950-1960s, multi-resistant Staphylococcus aureus was implicated to be major cause of antibiotic-associated diarrhea, especially pseudomembranous enterocolitis. In the late 1970s, a new type of antibiotic associated diarrhea, which is characterized by pseudomembranous colitis and lack of fecal multi-resistant S. aureus, usually following lincosamide administration, was recognized. Many studies have revealed the pathogenic roles of Clostridium difficile in these patients. Recent emergence of methicillin resistant S. aureus (MRSA) provokes another type of antibiotic-associated diarrhea. We have tried to isolate S. aureus and C. difficile from 150 faecal samples of patients with antibiotic-associated diarrhea. S. aureus alone was isolated from 32 (21.3%) samples. C. difficile alone was isolated from 51 (34.0%) samples, and, both were detected in 23 (15.3%) samples. 90.9% of S. aureus were MRSA. Comparing the clinical features of these cases, patients with both C. difficile and MRSA showed more serious clinical features. The patients who had undergone laparotomy were accompanied by shock and meteorism, more often than patients without laparotomy. The management of antibiotic-associated diarrhea due to MRSA is discussed. PMID- 1507433 TI - [Postoperative MRSA infections in digestive tract surgery]. AB - MRSA strains were first isolated in 1981 and have increased markedly from 1985 in our surgical ward. One hundred and ninety four strains of MRSA were isolated and 81 cases developed critical infections which were associated with enterocolitis, pneumonia and sepsis. There were many cases in esophageal cancer patients. Bacteriological features of the MRSA strains clearly changed in 1985 from IV to II coagulase type, accompanied with high resistance for antibiotics. Our management against nosocomial infection for MRSA started from April 1988. The number of MRSA cases decreased in 1989, increased in 1990 and decreased again in 1991. We are confident that our management is effective and we will take further efforts to choose the most adequate antibiotics after surgery in our surgical ward. PMID- 1507434 TI - [MRSA infections in multiple trauma patients]. AB - Multiple trauma patients requiring prolonged intensive care are at high risk of MRSA infections. Surgical debridement and proper antibiotic prophylaxis combined with isolation of this compromised host from indigenous bacteria are the mainstays of initial therapy to prevent this complication. If this develops postoperatively, the sites of infection vary among the patients, such as urinary tract, surgical wounds, the abdomen, respiratory tract, vascular catheters, etc. Clinical evidence of sepsis suggests that intra-abdominal and respiratory tract infection are major contributors to mortality. In a postoperative multiple trauma patient, with pneumonia, thoracic empyema, intraabdominal abscess, wound infection and sepsis caused by MRSA, surgical drainage of the abscess with systemic infusion of vancomycin was effective and resulted in full recovery. PMID- 1507435 TI - [MRSA infection and toxic shock syndrome in burn patients]. AB - In burn patients, MRSA was detected in the wound from the early stage to the wound closure stage. It is after the middle stage that sepsis by MRSA occurs. In comparison with Gram-negative bacilli, MRSA caused fewer sudden deaths, except for complications of toxic shock syndrome (TSS); MRSA was not considered to have a significant effect. The presence of a path of invasion into the blood other than the wound was suspected. Investigation of 35 Staphylococcus aureus sepsis patients (25 infected with MRSA) revealed that diagnosis is difficult when severe TSS occurs as a complication in sepsis. No correlation was found between toxic shock syndrome toxin-1 production by the bacterium detected and the onset of TSS. These findings suggest strong dependency upon the action of another toxin or endotoxin produced by Staphylococcus aureus and upon the immune condition of the host. PMID- 1507436 TI - [MRSA sepsis of premature infants]. AB - During the 12 year period from 1978 to 1990, 112 mature newborn and premature infants were diagnosed as sepsis in our nursery. The first case of MRSA sepsis was found in 1985. Since then, cases abruptly increased in number and 31 cases were found in total. Seven cases died and 24 were cured. Antibiotics such as AMK, MINO, IPM were effective. As the sensitivity of these drugs has been gradually dropping, we believe that VCM will be selected as the first choice. Early diagnosis and therapy are most important. Daily measurement of low level CRP (0.1 to 1.0 mg/dl) is useful and careful management is necessary in the course of significant PDA. PMID- 1507437 TI - [MRSA infections in the neonatal unit]. AB - MRSA infection in the neonatal unit is discussed, presenting our experience of an epidemic of TSST-1-positive strains in the Teikyo University Hospital in 1988 1989. Neonatal MRSA infections were experienced for the first time in 1982, and a few cases were treated each year from 1984 to 1987. In October 1988, MRSA colonized and/or diseased cases increased abruptly after admission of several MRSA-positive neonates. The new strains were TSST-1-positive, coagulase type II organisms, which were multiply resistant, including gentamicin. The disease/colonization ratio was 37.0% in 108 colonized neonates. Among them, 5 cases of atypical TSS were experienced. The main clinical manifestation was an abrupt onset of shock with leukopenia. Some of the cases were afebrile and rash was hard to recognise. For the successful treatment of neonatal TSS, not only effective antibiotics but also prompt exchange transfusions were needed. PMID- 1507439 TI - [MRSA infections in otorhinolaryngology]. AB - Infections caused by MRSA in otorhinolaryngology were evaluated in this study. From October 1990 to the end of September 1991, MRSA was detected in one hospitalized patient and 14 outpatients of the otorhinolaryngology department. MRSA was detected in the tonsils of five patients other patients--including four with cancer and other underlying diseases. In two of the four patients with chronic otitis media, otorrhea was stopped by disinfecting external ear toxin. Osteomyelitis of the upper jaw in neonates and infants must be treated in consideration of MRSA, as it is a hospital infection caused by cephem-resistant Staphylococcus. PMID- 1507438 TI - [MRSA ocular infections]. AB - Staphylococcus aureus and Staphylococcus epidermidis are organisms that frequently cause conjunctivitis, keratitis and endophthalmitis. MRSA comprised about 25% of the S. aureus isolated from ocular infections; most were from compromised host. MRSA was resistant to penicillins, cephems and macrolides but was sensitive to amikacin, netilmicin, minocycline and ofloxacin. Ofloxacin resistant strains, however increased rapidly. Topical vancomycin, arbekacin and minocycline were used when commercially available antibiotics were inadequate. PMID- 1507440 TI - [Methicillin-resistant Staphylococcus aureus in dermatology]. AB - Staphylococcus aureus (SA) is among the most important causes of skin infections. The incidence of Methicillin-resistant SA (MRSA) strains isolated from skin and skin structure infections was about 20-40%. In deep-seated pyoderma such as furuncle and furunculosis, MRSA was more frequently isolated than in other type of infectious diseases of the skin. But the incidence was gradually increasing. As to coagulase typing, type IV was most frequently isolated in MRSA. The damaged skin is easily colonized by high numbers of SA on its surface and within hair follicles. Through the indwelling catheters or decubitus SA on the skin could cause easily severe systemic MRSA infections such as sepsis or endocarditis of in patients. PMID- 1507441 TI - [MRSA infection in urological field]. AB - During the 12-month period ending December 1990, urological infections due to MRSA were found 18 patients (14 hospitalized and 4 outpatients) and clinical features of these cases were reviewed. Ten patients with MRSA in the urine were asymptomatic, but MRSA sepsis due to severe pyelonephritis occurred in one patient and extensive treatment was required. Factors contributing to MRSA infections were mainly indwelling catheterization, preceding antimicrobial therapy (new quinolones and new cephems), and obstructive disease. Strict management of indwelling catheters and drainage of wounds is especially important, because MRSA infections are considered to be nosocomial. PMID- 1507442 TI - [MRSA infections in obstetrical and gynecological fields]. AB - The rate of isolation of S. aureus from the materials collected from the genital tract in gynecological and obstetrical fields is very low about 11.5%. The chances to encounter infections caused by MRSA are therefore few. The countermeasures for the important infections caused by MRSA, nosocomial infections, become more important hereafter. Greater attention to MRSA in obstetrical field, especially, in the perinatal period, such as mastitis in puerperium and infections in high risk infants is necessary. PMID- 1507443 TI - [Methicillin-resistant Staphylococcus aureus infection in the orthopaedic field]. AB - A retrospective report regarding MRSA infections, related to wards and physicians in the hospital, was carried out. The number of the patients infected by MRSA in every wards was compared. Less patients with MRSA infection ware observed in the orthopaedic ward. An epidemiologic study using culture sampling of MRSA was performed at the isolated room for the patient with MRSA infection. Positive cultures were also detected in several areas in the ward, in addition to that room. Then the infection risk of every places in the hospital was suspected. Four cases of orthopaedic patients with MRSA were described. PMID- 1507444 TI - [Methicillin resistant Staphylococcus aureus (MRSA) infection in geriatric hospital--management for infected decubital ulcer]. AB - Wide spread of MRSA infection in geriatric hospitals indicated two important problems which must be resolved. One is how we can eradicate MRSA in the elderly, and the other is how we can control cross infections of MRSA within the hospital. The presence of infected decubital ulcers in the elderly make it difficult to answer these problems. Usually, MRSA and Pseudomonas aeruginosa which is isolated from decubital ulcers act as colonizers on the surface of granulated wounds but do not contribute to clinical symptoms. However, these colonizers can be the source of cross infection toward other debilitated patients. The actual management for decubital ulcer infected by MRSA are discussed from the above viewpoints. PMID- 1507445 TI - [Post-antibiotic effect and clinical significance]. AB - The postantibiotic effect (PAE) is the phenomenon of suppression of bacterial growth after brief antimicrobial exposure to microorganisms. The presence of PAE may be an important consideration in designing antibiotic dosage regimens. Antimicrobials with minimal or lesser PAEs may require serum concentration above MIC or entire dosing interval. Several antimicrobial actions are affected on the PAE phase, eg. "postantibiotic sub-MIC effect". Moreover, the PAE may contribute to the efficacy on host-parasite relationship. This phenomenon is discussed. PMID- 1507446 TI - [Considerations on MRSA infections in relation to modern chemotherapy]. AB - Before the antibiotic era of medicine began about 50 years ago, the prognosis for patients with severe staphylococcal infections was extremely poor. In the early 1940s, the introduction of penicillin G (PCG) temporarily solved the problem of staphylococcal infections, but the continued use of this agent caused the selection of resistant strains, which produced penicillinase. Accordingly, the value of PCG had seriously reduced by 1948. By then S. aureus had acquired multiple resistance to virtually all available systemic antibiotics, including aminoglycosides, tetracycline, chloramphenicol and the macrolides. The introduction of the semisynthetic penicillinase resistant penicillins (e.g., methicillin, oxacillin) and the 1st generation cephems brought about a general decline in the prevalence of multiply resistant S. aureus during the early 1960s. The strains of methicillin-resistant S. aureus (MRSA) were initially detected in 1961 in the United Kingdom, shortly after methicillin came into clinical use, and they have subsequently been isolated in many other parts of the world including Japan. In Japan, most strains of MRSA now represent high level resistance to all antibiotics, except for a few antibiotics, such as vancomycin and arbekacin, and therefore, they posed a serious problem clinically and epidemiologically, via immuno-suppressed inpatients, in particular, as the causative pathogen of nosocomial infection. The appearance and spread of such MRSA strains in Japan may be due to the extensive use of broad spectrum antibiotics, particularly the 3th generation cephems. It is now important to reconsider the modern chemotherapy which evoke serious drug-resistant mutants, such as MRSA. PMID- 1507447 TI - [Basic aspects of Staphylococcus aureus and MRSA--typing and extracellular toxins and proteins]. AB - Many kinds of staphylococcal typing systems have been developed and tested for epidemiology of Staphylococcus aureus. Coagulase typing and phage typing are more useful and important for this epidemiology. The methods of coagulase typing and phage typing were discussed in this paper. A large number of toxins and proteins of Staphylococcus aureus have been released in the field of infectious environment. Some of these toxins and proteins, working as causative agents of staphylococcal infection, are of interest and discussed here. MRSA shows the same mechanisms of infection as methicillin sensitive Staphylococcus aureus. PMID- 1507448 TI - [Molecular genetics of MRSA]. AB - Methicillin resistance in staphylococci is explained by any of the several alterations of penicillin-binding proteins. In most (97%) of the cases, however, it is caused by acquisition of mecA gene. The mecA gene seems to be laterally transmissible among various staphylococcal species, although the frequency of transmission may not be high in view of the observed rather homogeneous nature of genetic backgrounds of the MRSA strains which were isolated all over the world. Evolution of MRSA to acquire higher level of resistance to beta-lactam antibiotics has been noticed in recent years. Such phenotypic evolution is explained by a genetic alteration involving the mec regulator genes, mecR1 and mecI, of the prototype MRSA strain. PMID- 1507449 TI - [A guide to prevent infectious disease due to MRSA]. AB - Now in Japan, infectious diseases due to MRSA is an important problem to solve and it has a growing social interest. It is clearly associated with hospital infections. So most important thing for us is to prevent and treat properly hospital infections. As a result of thorough investigations in a hospital for aged persons and a general hospital, we developed some guidelines to prevent MRSA infections. It is necessary to have a prevention committee in the hospital which will do the followings: Reveal the present condition of hospital infections by thorough investigations, make appropriate choice of antibiotics, good care of patients having infectious diseases due to MRSA, good care of carriers, better use of disinfectants, and education of medical staffs. PMID- 1507450 TI - [Incidence and antimicrobial susceptibility of clinical isolates of MRSA from 1988 to 1990, from the results of 26 clinical laboratories in Tokyo and the surrounding area]. AB - We made a survey to investigate the incidence of clinical isolation and the trend of antimicrobial susceptibility of Methicillin-resistant Staphylococcus aureus (MRSA), isolated in 26 clinical laboratories. Among the 26 institutions, the frequency of MRSA was 22 to 64% (average: 42.1%) in 1988, 22 to 69% (average: 55.3%) in 1989 and 29 to 76% (average: 56.9%) in 1990, and increasing year by year. MRSA showed poor sensitivity to beta-lactam antibiotics, gentamicin, toburamycin and clindamycin. There was a significant difference in frequency of the minocycline-resistant strains and the ofloxacin-resistant strains among the 26 institutions. Albekacin, netilmicin, and vancomycin were most active against MRSA with a MIC90 of 1, 8 and 1 microgram/ml, respectively. PMID- 1507451 TI - [Survey of MRSA infection in Ibaraki-ken--Ibaraki Association for infectious diseases]. AB - This study which was undertaken at several major hospitals in Ibaraki-ken revealed that, 1) the proportion of Staphylococcus aureus in all the isolates ranged from 5% to 17% and the prevalence of MRSA in isolates of Staphylococcus aureus varied from 51% to 82% depending upon each individual hospital. 2) the clinical response to FOM and CMZ combination therapy was 88.9% and, to FOM and CZON was 57.1% showing no statistical differences between the two regimens. 3) in vitro analyses assessed by the FIC index of 251 isolates revealed that FOM had an additive or synergistic effect with CMZ in 53.8%, with CZON in 66.9%, with minocycline (MINO) in 43.8%, with cefamandole (CMD) in 61.8%, with cefazolin (CEZ) in 62.9% and with imipenem/cliastatin sodium (IPM/CS) in 68.9% at all isolates. 4) the cumulative curve of susceptibility to single CMZ and the combination of CMZ and FOM revealed that the blood levels of CMZ at 3 hours after intravenous administration covered 57% of isolates when used alone and 82% of isolates when in combination with FOM. The blood levels of CZON at 3 hours covered 5% of isolates when used alone and 41% when in combination with FOM. The extent of the therapeutic effect increased from 6% to 42% by CMD, from 12% to 54% by CEZ, from 20% to 58% by IPM/CS and from 78% to 84% by MINO. The combination of CMZ and FOM was found to be the most effective for enhanced effects on MRSA in vitro. PMID- 1507452 TI - [Methicillin-resistant Staphylococcus aureus (MRSA) isolated in hospitals in Fukuoka City area]. AB - Bacteriological and clinical studies were carried out on 280 strains of Staphylococcus aureus isolated in hospitals in Fukuoka city area from September 1990 to March 1991. Of all S. aureus strains studied 116 (41.4%) were methicillin resistant. The proportion of MRSA in S. aureus isolates from outpatients was 10% (11/109), 69.2% (90/130) in those from inpatients. The average age of patients with isolated MRSA was 70.5 +/- 16.9 years and that of patients with isolated MSSA, 44.2 +/- 29.3. MRSA strains were recovered mainly from sputum and pus. The isolation rate did not vary significantly with hospitals of different size (number of beds). Of all MRSA strains 48 (41.3%) produced coagulase type VII. As for drug susceptibility, MRSA strains with coagulase type VII were more sensitive to clindamycin and more resistant to minocyclin compared to MRSA with other coagulase types. PMID- 1507453 TI - [Isolation and antimicrobial susceptibility of methicillin-resistant Staphylococcus aureus (MRSA) at Kumamoto University Hospital]. AB - An increasing prevalence of methicillin-resistant Staphylococcus aureus (MRSA) has created a serious therapeutic problem. During the period from July to December 1987, the prevalence of MRSA was only 72 strains (35.8%) of 201 total staphylococcal isolates. Since then, the frequency of MRSA has markedly increased to 67.3% in 1989, and at that time it was estimated that 30 patients (3.5%) of 850 total inpatients became infected with MRSA. In an early study in 1987, the majority of the MRSA came from post-operative patients; however in 1989, nearly 40% of MRSA were from internal medicine, mainly from immunocompromised patients. The major source of MRSA isolates was sputum (40%) throughout the years, but the MRSA from blood cultures was first recovered in 1989. Also, the major coagulase serotype of MRSA was type IV (18 of 30) in the 1987-study, then shifted to type II (24 of 40) in 1989. Among the several antimicrobials evaluated, four agents; erythromycin, minocycline, ofloxacin, and gentamicin revealed increasing MICs when compared with the results obtained for the MRSA isolates in 1987 and 1989. In particular, the most of the MICs to minocycline and ofloxacin were categorized to be highly susceptible (less than or equal to 0.39 micrograms/ml) or resistant (greater than or equal to 25 micrograms/ml). Vancomycin, currently licensed for the MRSA infection, will be highly effective both in vitro and in vivo; however, it examinative of the MRSA isolates in the clinical laboratories, especially to prevent hospital-acquired infections and to follow up the vancomycin susceptibility will be required. PMID- 1507454 TI - [Typing of methicillin-resistant Staphylococcus aureus by antibiotic resistance phenotypes as an epidemiological marker in nosocomial infections]. AB - A total of 129 clinical isolates of methicillin-resistant Staphylococcus aureus was tested for the susceptibility to 28 antibiotics, antiseptics and heavy metal salts, according to the method of Gillespie et al. The strains showed resistance ranging from 20% to 80%, to 10 agents, such as amikacin, chloramphenicol, clindamycin, gentamicin, neomycin, streptomycin, tobramycin, acriflavine, cadmium nitrate, ethidium bromide. These agents were finally chosen for typing in this study. Strains resistant to 10 agents were distributed into 55 phenotypes. Most strains isolated from one ward belonged to the specified phenotype, whereas strains isolated from other wards were divided into a variety of phenotypes. It seemed to be the occurrence of nosocomial infection in this hospital. This typing method gives the merit to be easy, economical, rapid and reproducible for the epidemiological investigations in the clinical bacteriological laboratory. PMID- 1507455 TI - [An assessment of nosocomial infections of methicillin-resistant Staphylococcus aureus based on coagulase typing and phage typing]. AB - An epidemiologic investigation was carried out in Ogaki Municipal Hospital to clarify the status of nosocomial MRSA Infection between 1989 and 1991. In 1989, coagulase type IV, enterotoxin A-producing, and phage group I strains, which were highly resistant to multiple antibiotics and isolated in the internal wards, accounted for 43.4% of all MRSA strains clinically isolated in the entire hospital. In 1990, coagulase type II strains that were sensitive to GM but resistant to FMOX and IPM increased. There were significant differences in the frequency of detection of various strains among wards, suggesting an inter-ward variation in MRSA strains. Changes in environmental strains reflected those in clinical strains. The findings suggest the necessity of measures not only for long-hospitalized MRSA carriers themselves but also for the environment of patients, medical staff, and those taking care of patients. PMID- 1507456 TI - [Genomic DNA fingerprinting by pulsed-field gel electrophoresis for study of nosocomial infection caused by methicillin-resistant Staphylococcus aureus]. AB - In this study, we have compared genomic DNA fingerprintings among isolates of methicillin-resistant Staphylococcus aureus (MRSA) by using pulsed-field gel electrophoresis (PFGE). Chromosomal fragments digested with Sma I were most suitable for the PFGE separation, giving 15-20 fragments of sizes ranging from about 30-1,500 kb. Thirty-one distinctive fragment patterns were identified in 111 isolates of MRSA. On the basis of the genomic typing by PFGE, we performed an epidemiological investigation of an outbreak of nosocomial MRSA infection among 18 inpatients in Nagoya University Hospital. Ten types of chromosomal digestion were identified in 21 isolates of MRSA. The clarity and polymorphism of the chromosomal digestion patterns enabled us to discriminate between isolates. Classification of the genomic DNA fingerprinting patterns by PFGE is therefore proposed as a useful method for investigating the source, transmission, and spread of nosocomial MRSA infections. PMID- 1507457 TI - [Carrier state and comparative study of methicillin-resistant Staphylococcus aureus from the staff and patients]. AB - The nasal carriage of Staphylococcus aureus in 529 staff was screened. S. aureus from staff and patients whose minimum inhibitory concentration (MIC) of methicillin was larger than 12.5 micrograms/ml by agar dilution was defined as Methicillin-resistant S. aureus (MRSA). Coagulase typing was performed by DENKA SEIKEN kit. Hands of ward staff were screened before and after contact with the MRSA carriers and after hand washing. The nasal acquisition rate of S. aureus and MRSA for staff was 27.6% and 8.5%. The rate of ward staff for nasal carriers of MRSA was 91.1%. Coagulase type II strains from ward staff and inpatients were dominant. In some cases MRSA was detectable after hand washing: In MRSA infection ward staff played a dangerous role as a vector. PMID- 1507458 TI - [Selection of laboratory tests in primary care situation and solution to the problems]. PMID- 1507459 TI - [The application of medical information to hospital laboratory]. PMID- 1507460 TI - [Physicians' assessment of laboratory interpretive reporting system]. PMID- 1507462 TI - [A trial for automated laboratory data classification of protein fraction data]. PMID- 1507461 TI - [Automated categorization of protein electrophoretic patterns]. PMID- 1507463 TI - [Pattern analysis of protein electrophoresis data]. PMID- 1507464 TI - [Usefulness of matrix discrimination in screening of hepatobiliary disorders]. PMID- 1507465 TI - [Tools for supporting the decision making process of clinical laboratory use. Decision analysis]. PMID- 1507466 TI - [Psychological factors related to clinical judgment and decision]. PMID- 1507467 TI - [Nucleic acid probes in infectious diseases]. AB - DNA probes are then newest diagnostic reagents now in clinical use to detect or specify infectious microorganisms. The fundamental aspects of DNA probes and their clinical applications are reviewed to provide the clinician new information on the recent progress in infectious diseases. PMID- 1507468 TI - [Biosensors and clinical analysis]. AB - Method for the selective determination of organic compounds in biological fluids, such as blood, are very important in clinical analyses. Most analyses of organic compounds can be performed by spectrophotometric methods based on specific enzyme catalyzed reactions. However, on account of the complicated procedure, these methods cannot be applied directly to bed-side monitoring. Alternatively, biosensors based on enzymes and electrochemical transducers possess excellent sensitivity for biological substrates and can determine directly a single compound in a biological fluid without need for a prior separation step. Therefore, in several years, many kinds of biosensors have been developed, and implantable microbiosensors for a body organ have also been reported. In the near future, an artificial pancreas fabricated by micromachine technology will be developed. PMID- 1507469 TI - [Application for medical field of enzyme sensor]. AB - Various portable glucose sensors have been developed and used for self measurement of blood glucose levels for diabetes. Enzyme sensors will become one of a useful technology for assay of various substances and be applied to analysis for clinical chemistry. PMID- 1507470 TI - [Utilization of an enzyme-sensor in clinical medicine]. AB - The utilization and merit of an enzyme-sensor for measuring serum- or urine components were reported. The enzyme sensor (enzyme-electrode) is an H2O2 electrode, O2-electrode or ion selective electrode connected with an enzyme immobilized nylon tube. First, the principle of measurements with an enzyme sensor was reported. Secondly, and H2O2 electrode which had been planned and developed in our laboratory was introduced. The outline of our apparatus and the procedure of enzyme-immobilization onto a nylon tube wall were explained. Then the results obtained from quantitative analysis of serum- and urine-components were shown. For the analysis by our apparatus, 3-60 microliters of serum or urine was used and incubation time was approximately 5 min. The results obtained by our apparatus coincided with those obtained by other methods (r = 0.981-0.997). Thirdly, the usefulness of commercial instruments with an enzyme-sensor for determining glucose- or lactic acid-content was described. The results (glucose and lactic acid-contents) measured by desktop-size instruments showed a high lineality and good reproducibility (CV = 0.6-1.5% in glucose and 0-0.7% in lactic acid). A good correlation was observed among each instrument (r = 0.999). The results by card-size instruments, GLUTEST E or ExacTech, showed a lower reproducibility (CV = 4.1-6.5%) and correlation (r = 0.95-0.98) than those by desktop-size instruments. PMID- 1507471 TI - [Biosensing techniques for the laboratory medicine]. AB - Biosensing techniques are utilized in micro analysis of the biological constituents with an integrated device. Their applications to laboratory medicine are of great interest. Recently, several types of micro electrodes or ion sensitive field effect transistors (ISOFET) were developed. For fabrication of the biosensor selection of the proper bio-element and transducer to assay our sample, is important. In this article we will indicate some items on the future prospect of biosensing techniques for laboratory medicine. PMID- 1507472 TI - [Clinical usefulness of essential laboratory tests]. AB - Clinical usefulness of Essential Laboratory Tests (1), proposed by Japan Society of Clinical Pathology, was retrospectively evaluated in 500 outpatients who first visited the medical clinic of a prefectural general hospital. Sixty percent of the patients were diagnosed with gastrointestinal disease or respiratory disease. Performance rates of urinalysis, blood counts, serum total protein, A/G ratio, C reactive protein, erythrocyte sedimentation rate and fecal occult blood were 87.6%, 55.8%, 49.6%, 48.8%, 37.8%, 10.0% and 5.6%, respectively. Abnormal test results rate of urinalysis, blood counts, serum total protein, A/G ratio, C reactive protein, erythrocyte sedimentation rate and fecal occult blood were 12.3%, 12.9%, 14.1%, 5.7%, 21.6%, 22.6% and 25.9%, respectively. The clinical diagnoses and the abnormal test results indicated that the patients general condition was assessed properly from the A/G ratio, 92% of patients with proteinuria were transient cases and urobilinogen has poor sensitivity and specificity for the diagnosis of liver diseases. PMID- 1507473 TI - ["Essential laboratory tests" in primary care medicine--experiences in Comprehensive Medicine, National Defense Medical College]. AB - The "essential laboratory tests" were applied to 1,026 new patients visiting the outpatient unit of Comprehensive Medicine, National Defense Medical College, to determine the usefulness of these tests in primary care medicine. The "essential laboratory tests" have contributed to the establishment of the initial diagnosis or confirmation of the "tentative initial diagnosis", and to the estimation of the nature or degree of seriousness of the disease. In addition, other diseases not related to the patient's chief complaint could be screened in 32% of the new patients examined with these tests. The "essential laboratory tests" were also found to be useful for the estimation of the presence of malignant tumors in 12 patients with various kinds of malignancies as well as the estimation or evaluation for such conditions as infection or inflammation, anemia, liver or renal dysfunction, and the ambulatory screening of metabolic diseases including hyperlipidemia, liver or urinary tract diseases. In conclusion, simultaneous performance of the "essential laboratory tests" with the history taking and the physical examination will provide important medical information in primary care medicine. PMID- 1507474 TI - [The effectiveness of the essential laboratory tests in daily primary care--view of a physician at a private clinic]. AB - I put into practice, "The essential laboratory tests (a proposal)" published by Japan Society of Clinical Pathology in 1989 on new patients who visited my clinic. It was useful not only for screening of diseases, but enhanced the probability of diagnosis. I could discover hidden abnormalities unrelated to the patient's complaints. Therefore, the condition of the patient could be judged theoretically and scientifically by the use of the essential laboratory tests. PMID- 1507475 TI - [Proper use of laboratory tests from a perspective of health insurance administration]. AB - The national medical expenditure increases at a rate of 1 trillion yen a year, and the expenditure for 1992 is estimated to be about 23 trillion yen. One of the most important jobs of the Health Insurance Administration is to control the medical expenditure. Every time the medical fee is amended, laboratory tests are always the target of the cost containment. In the past, the biochemical tests have been separated into the cost for performance of test, and the cost for assessment of the results, the cost of tests for specific diseases has been comprised, or fixed, and the fee of EKG, EEG, Echo etc after the first has been forced to be reduced. These are all administrative policies, but ultimately, they must be selected properly by the physician who requests these tests. In the future, a system should be established which enables the physician to efficiently (cost-efficiently) select the most appropriate test. For this purpose, undergraduates and post-graduates should learn the concepts of clinical epidemiology and clinical economics. These academic disciplines should be incorporated to increase the value of the treatment. Furthermore, the physician should be given economical incentive of proper use of medical resources. PMID- 1507476 TI - [Current status and problems of platelet function tests]. AB - Platelet function tests have been utilized for a long time as a useful tool for the diagnosis of qualitative platelet disorders. However, recently reports suggest that platelet function tests currently available in routine laboratory do not necessarily reflect in vivo hemostatic states. First of all, bleeding time could sometimes be non-informative for the following reasons; 1) Duke method, the most popular method in Japan, has poor reproducibility, 2) there is no appropriate method for monitoring of aspirin ingestion, 3) prolongation of bleeding time does not correlate with the amount of blood loss during surgery. Platelet adhesion is still measured by the ability of platelets to be retained on glass beads. However, this test is unable to detect selectively platelet adhesion. Thus, the test in which platelets can exclusively adhere to subendothelial components such as collagen, may be required. Platelet aggregation has been mostly analyzed by the changes in light transmittance in platelet rich plasma (PRP) with a platelet aggregometer. However, this test totally depends on the platelet count in PRP or duration of time after taking blood from patients. Moreover, platelet aggregation in this system is optimally observed and is hardly detectable when the in vivo Ca++ concentration has been chelated. Furthermore, the test could not detect small platelet aggregates, thus being unable to measure the early phase of platelet aggregation. These observations suggest that more simple and specific tests should be developed and become available in routine laboratory. PMID- 1507477 TI - [Platelet adhesion and adhesive proteins--how to measure the platelet adhesiveness]. AB - We examined, platelet adhesive function in vivo by comparing the platelet retention rate (PRR) with other laboratory tests. In 71 patients, PRR did not correlate with bleeding time (BT), ristocetin-induced platelet agglutination (RIPA), vWF:AG, vWF:RCo, FVIII:C, fibrinogen, platelets counts or platelet aggregation tests. Among them, the coincidence rate of PRR with BT seems relatively better than that of other tests. In patients with Bernard-Soulier syndrome (BSS), PRR, RIPA and high shear-induced platelet aggregation (SIPA), measured using a cone-plate type instrument, were decreased, while platelet adhesion in a static system and SIPA at a low shear rate were normal. In patients with Glanzmann's thrombasthenia (TA), PRR and SIPA were decreased at both high and low shear rates, while RIPA and platelet adhesion were normal in a static system. In patients with deficient glycoprotein Ia/IIa complex which is one of the putative receptors for collagen, platelet adhesion in a static system is markedly decreased. In patients with von Willebrand disease, the pattern of platelet adhesion tests was similar to that of BSS patients, while in patients with afibrinogenemia, it was similar to that of TA patients except for SIPA at a high shear rate. The various experiments using monoclonal antibodies support these abnormalities. These findings, suggest that PRR is a suitable screening test, but further rapid and easy tests will be necessary to diagnose the defects of platelet adhesion at various shear rates. PMID- 1507478 TI - [Clinical evaluation of four tumor markers (CEA, TPA, CA50 and CA72-4) in colorectal cancer]. AB - In a total of 194 cases, consisting of 86 cases of colorectal cancer undergone operation later, 7 cases of non resectable cancer, 34 cases of recurrence, 43 cases of NED (no evidence of a recurrence after radical surgery for colorectal cancer) and 24 cases of benign colorectal disease, serum CEA, TPA, CA50 and CA72 4 levels were determined. The positivity rate was high for all four markers in stage V cases among 86 cases of colorectal cancer, and in cases of non resectable cancer and cases of recurrence. The highest positive rate was obtained with CEA. On the contrary, in cases of stage I to IV the positivity rates of these four tumor markers were as low as 0 to 34.8%. Out of 127 cases of colorectal cancer excluded of 43 NED cases, 52 cases were negative for all four tumor markers and 14 cases were positive only for CEA. In 49 cases, CEA and at least one of the other three tumor markers gave positive results. In 12 cases, CEA gave negative results and at least one of the other three tumor markers positive results. In conclusion, measurement of blood levels of these tumor markers is limited of its usefulness in early diagnosis of colorectal cancer. However, in the diagnosis of advanced stage and of recurrence during the postoperative follow-up period the measurement of tumor markers provides useful information. CEA is most sensitive among the four tumor markers tested and any combination of these four markers is not advantageous because of an increase in false positivity rate. PMID- 1507479 TI - [Increased serum levels of human cardiac myosin light chain 1 in patients with renal failure]. AB - In this study, we measured cMLC1 concentration in serum and urine from patients with acute myocardial infarction (AMI), chronic renal failure (CRF), and various grades of renal dysfunction (RD) in comparison with normal controls, by using enzyme immunoassay (EIA) with monoclonal antibody, and attempted to elucidate the mechanism of increased serum level of cMLC1 in patients with renal failure. The serum level of cMLC1 of CRF patients under maintenance hemodialysis (HD) was 20.3 +/- 19.6 ng/ml, markedly higher than normal controls (0.54 +/- 0.55 ng/ml). The patients with RD and CRF under conservative therapy had higher serum cMLC1 level than normal controls especially in advanced CRF, while each value not correlating with their creatine clearance (Ccr). cMLC1 in urine was detectable in only two cases with AMI accompanied with CRF or RD. In addition, immunohistological studies of renal biopsy specimens from RD patients did not show cMLC1 deposits in glomerulus. These results suggest that cMLC1 is assumably filtered through the glomerulus, and then absorbed in the renal tubule. PMID- 1507480 TI - [Identification of two different genetic mutation associated with silent phenotypes for human serum cholinesterase in Japanese]. AB - Two different gene mutations associated with the silent phenotype for human serum cholinesterase were demonstrated. DNA from five individuals with silent gene phenotype of three unrelated Japanese families was amplified by the polymerase chain reaction (PCR) and analyzed by direct sequencing. The first instance demonstrated a G----C transversion at codon 365 from GGA (Gly) to CGA (Arg), which was seen in three individuals of the two families. This mutation was resulted to create a new Taq 1 restriction site (TCGA). The second mutation was shown by a double heterozygous condition with two different silent gene mutations in two members of remaining one family. These mutations were as follows: 1) one type was a frameshift mutation, in which an extra A was inserted in codon 315 (ACC----AACC) to create a new stop codon at position 322 and 2) the other was the same point mutation at codon 365 as seen in the first instance. These results indicated that many silent variants can be distinguished by direct sequence analyses of genomic DNA. PMID- 1507481 TI - [Detection of methicillin-resistant Staphylococcus aureus using PCR and non radioactive DNA probe]. AB - Two commonly used diagnostic tests for Staphylococcus aureus (MRSA) are cultivation of bacteria from clinical samples on mannitol-salt agar plate or on MRSA-screen agar plate with oxacillin. However, the use of PCR and DNA probes is considered more rapid and sensitive, as staphylococcal cells have high resistance to beta-lactam due to the novel penicillin-binding protein, PBP2'. Therefore, three different pairs of DNA primers (P1F-P1R, P2F-P2R and P3F-P3R) complementary with unique regions of the MRSA PBP2' gene were synthesized for use in polymerase chain reactions with DNA of MRSA. Amplified target DNA of 466, 480 and 630 bp could be resolved on ethidium bromide-stained gels, and hybridized with DNA probes conjugated to alkaline phosphatase. When applied to pure cultures on the MRSA screen agar, the DNA probes detected MRSA in 180 of 196 (P1F-P1R), 72 of 83 (P2F-P2R) and 66 of 71 (P3F-P3R) culture-positive specimens (accuracy range, 86.7 93.0%), while 61.6-89.3% of MRSA were detectable in culture-positive specimens streaked on the mannitol-salt agar. When applied directly to clinical samples, this DNA probe assay detected MRSA in culture-positive specimens within an accuracy range of 50.0-79.3%. It was thus clear that comparison of cultivation and DNA hybridization results yields good correlation with respect to detection of MRSA. These results suggest that the DNA probe assay may be useful in complementing existing culture techniques. PMID- 1507482 TI - [Clinicobacteriological study of Pasteurella multocida infection as a zoonosis. (2)--Comparisons of P. multocida separated from patients and their pet dogs and cats]. AB - A total of 17 strains of Pasteurella multocida, of which 13 were isolated from patients treated at Nihon University Itabashi Hospital or Nihon University Surugadai Hospital between April, 1984 and March, 1991 and 4 from 1 dog and 3 cats kept by the patients, were evaluated with respect to their biochemical properties, sensitivity to drugs, and serotype. The isolated strains were all considered to be Pasteurella multocida subsp. multocida because of the agreement of their responses to indole, sorbitol and dulcitol with those of this subspecies, except for 1 sorbitol-negative strain of Pasteurella multocida subsp. septica isolated from 1 patient who had been bitten by a cat. All the isolated strains showed high sensitivities to various drugs. The serotype was capsular type A, which is often observed in cats and dogs, in 7 strains, which consisted of 6 of the 7 strains derived from the airway of the patients and 1 of the 6 strains derived from bit or scratch wound. The remaining strains could not be classified. Five morphological types, namely 1, 3, 3.8, 6, and 8 were observed. In 2 patients, Pasteurella multocida subsp. multocida of the same serotype was also isolated from their cats. One of these patients had intimate contact with the cat including kissing. Our findings suggest that: 1) Pasteurella multocida subsp. multocida has been responsible for most conventional cases of Pasteurella multocida infection. 2) Strains isolated from patients differ in the capsular type according to the disease.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1507483 TI - [Simple method for measurement of erythrocyte osmotic fragility]. AB - We developed a simple and quantitative method for determination of erythrocyte osmotic fragility, which is based on a logarithmic linearization of osmotic fragility curve and a calculation of three parameters, that is, C50 (the osmolarity causing 50% hemolysis), beta (the slope of the curve) and H (% hemolysis before treatment). By making use of personal computer program, calculation of the parameters and print-out of reports are automated. As the results, it takes only 30 min to finish all procedure. This method is very useful particularly for the laboratory screening of hereditary spherocytosis. PMID- 1507484 TI - [Correction of haptoglobin contents in hemolytic specimen with addition of saturated hemoglobin]. AB - Measurement of serum haptoglobin by immunoturbidimetry was markedly interfered with hemolysis because of haptoglobin-hemoglobin complex formation. Turbidity formed with haptoglobin and immunoglobulin complexes was gradually decreased by the addition of hemoglobin in the reaction mixture, and reached to a certain fixed levels when serum haptoglobin were saturated with hemoglobin. The turbidity derived from saturated haptoglobin and hemoglobin complex closely correlated with the haptoglobin level without hemoglobin. Thus, we could measure the corrected haptoglobin level in hemolytic specimen by the saturation of hemoglobin in reaction mixture. PMID- 1507485 TI - [Key note comment on the determination of glomerular filtration rate]. AB - Glomerular filtration rate (GRF) is the most fundamental renal function. Determination of GFR is the most important examination in clinical nephrology. Cin is accepted as the gold standard of GFR, but, continuous infusion and the determination method of inulin (method of anthrone) are very troublesome. Interference of glucose in the serum and urine of patients with diabetes mellitus on the determination of inulin should be avoided. Ccr is widely used in the clinical field. Recently, the dynamics of creatinine in the body have been clarified. Variation of pool, generation rate, extrarenal excretion and tubular excretion of creatinine are found to change daily in the patient. Additionally, classical Jaffe's reaction involves non creatinine chromogen particularly in the serum. Though Jaffe's reaction with kinetic analysis improves the reliability of this reaction, the result is still unsatisfactory. There are several methods of enzyme assay are now using an autoanalyser, but, if we use many enzymes and reagents, the reliability of this method could not exceed that of Jaffe's method. Recently, HPLC is recommended as the standard method. 24-hr urine collection is also troublesome in the measurement of Ccr. I have found a good correlation between the estimated Ccr using Cockcroft and Gault's formula and Cin. Such prediction using serum creatinine concentration and few parameters should be developed. Radiolabelled agents have been widely used for the determination of GFR. However, in Japan, the methods of clearance of non radiolabelled contrast agents should be developed. Furthermore, a physical determination of GFR is necessary. In this workshop, these issues will be discussed by each speaker. PMID- 1507486 TI - [Measurement of renal plasma flow and glomerular filtration rates in diabetic subjects]. AB - To clarify the problem in the measurement of renal plasma flow and glomerular filtration rates in diabetes, the effect of glucose on the determination of para aminohippuric acid (PAH) and inulin was examined. The concentration of urinary PAH in glucosuric diabetic subjects decreased after the storage of urine samples because of the glycation of PAH. Therefore, glucose must be removed by the acid treatment before the determination of the concentrations of urinary PAH. Since glucose can interfere with the assay of inulin, the sample must be treated with NaOH prior to the determination of the inulin concentration. GFR of the subjects with type 2 diabetes was next examined. GFR in the subjects with a duration of diabetes less than 10 years was significantly higher than that in the subjects with a duration of diabetes more than 10 years. Thus, the subjects with short term type 2 diabetes may present with hyperfiltration similar to the subjects with short-term type 1 diabetes. PMID- 1507487 TI - [A method for the simultaneous determination of iothalamic acid and creatinine clearance by coupled-column liquid chromatography]. AB - [125I]iothalamic acid clearance is used for the estimation of glomerular filtration rate. Therefore, we developed a coupled-column liquid chromatography for the simultaneous determination of iothalamic acid and creatinine in human serum and urine samples to calculate their clearance. The liquid chromatograph consisted of an automatic injector, four columns and four switching valves. Timing of sample injection and switching of valves were controlled by a combination of timer units. Diluted samples were injected into a column of weakly acidic ion exchanger (Asahipak ES-502C, 30 degrees C, C1), and iothalamic acid excluded from the column was purified by gel chromatography on a hydrophilic gel (Asahipak GS-320H, 50 degrees C, C2) and then by ion exchange chromatography on a weakly basic anion exchanger (Asahipak ES-502N, 50 degrees C, C3). Creatinine that was eluted from C1 after iothalamic acid was transferred to Asahipak GS-320H (37 degrees C, C4) and C1 was backflushed until 10 min before the next sample was injected. Samples were injected every 55 min. The mobile phase was a sodium propionate buffer prepared by dissolving 0.035 mol of NaOH and 0.35 mol of propionic acid in 1 kg of ultra pure water, and its flow rate was 1.1 ml per min. Creatinine clearance calculated from the data obtained by this method was higher than that obtained by Jaffe's method, because serum creatinine concentrations obtained by this method were lower than those obtained by Jaffe's method. Iothalamic acid clearance (y) calculated from the data on serum and urine samples of clearance time 105-135 min showed a close correlation with inulin clearance (x) calculated from the data obtained by the anthrone method, for which aliquots of the same samples were used (y = 1.066 x -1.429 ml/min, r = 0.997, n = 15). PMID- 1507488 TI - [A new analytical method for simultaneous measurement of iothalamate and iohexol]. AB - Glomerular filtration rate (GFR) is believed to be the overall index of renal function, and the renal clearance of inulin (Cin) obtained during constant intravenous infusion has long been accepted as the gold standard of GFR measurement. Because of a number of technical difficulties inherent in the assay of inulin concentration in urine and plasma, its utility in clinical practice is limited. Iothalamate, urographic contrast medium, which behaves and is excreted in a fashion similar to inulin, has been accepted as a good filtration marker. We examined whether GFR could be estimated by ionic contrast media, "iothalamate" and non-ionic contrast media, "iohexol", when the high-performance liquid chromatography (HPLC) system was used as the analytic method. In our HPLC system, iothalamate and iohexol could be simultaneously determined. The assay results gave linearity within the wide range of concentrations tested. In seventeen subjects, the renal clearances of creatinine, iothalamate, and iohexol (Ccr, Ciot, and Cioh) were compared with that of inulin. The slopes with zero intercept of Ccr vs Cin, Ciot vs Cin, and Cioh vs Cin were 1.24 +/- 0.02, 1.06 +/- 0.02, and 0.83 +/- 0.02, respectively. In conclusion, an excellent correlation of renal clearance of iothalamate with that of inulin was obtained in patients with a wide range of renal function and normal volunteers. This justifies the use of the single injection of iothalamate and HPLC system as the analytic method in the measurement of GFR. PMID- 1507489 TI - [Doppler ultrasound measurement of phasic renal arterial blood flow velocity in patients with chronic glomerulonephritis]. AB - The phasic renal arterial blood flow velocity was measured using a Doppler-Based Toshiba SSH-160A scanner in 25 healthy subjects and 78 patients with chronic glomerulonephritis. Renal arterial blood flow at the renal hilum was visualized with color Doppler ultrasound, and the velocity waveform was obtained by pulsed Doppler ultrasound. The velocity waveform was then analyzed to give the peak systolic velocity (S), end-diastolic velocity (D), resistive index (RI), and pulsatility index (PI). Creatinine clearance correlated with S (r = 0.76), D (r = 0.80), RI (r = -0.74), and PI (r = -0.85). The split renal glomerular filtration rate, calculated by a method which makes use of the early renal uptake of Tc-99m DTPA, also correlated well with these parameters. These findings suggest that renal arterial blood flow as detected by Doppler ultrasound may be useful for the noninvasive, direct, rapid, and simple evaluation of renal hemodynamics and renal function, although various modifying factors also need to be considered. PMID- 1507490 TI - [Clinical significance of urinary sediment dysmorphic red blood cells and casts in renal disease]. AB - We investigated the utility of measuring dysmorphic red blood cells (d-RBC) and urinary casts in the diagnosis and assessment of prognosis of renal diseases by evaluating these parameters in a total of 278 urine specimens from 78 patients with various renal diseases at our hospital. Urinary sediments obtained by the conventional method with in 4 hours after voiding were subjected to Sternheimer and Malbin's staining and examined under a conventional light microscope. We used the criteria we previously devised for classification of RBC as d-RBC and for classification of casts hyaline, granular, epithelial, red blood cell, white blood cell, fatty, or waxy. When there were 5 or more urinary sediment red blood cells per high-power field, d-RBC was found in 94% of samples from patients with chronic glomerulonephritis. The finding of d-RBC was not related to glomerulonephritis pathologically diagnosed according to the WHO classification system for biopsy specimens. Even when there were fewer than 5 red blood cells per high-power field, d-RBC was sometimes found. Casts of all types were found in samples from patients with chronic glomerulonephritis or chronic renal failure. In samples from patients with chronic pyelonephritis, however, white blood cell, fatty, and waxy casts were not found, and less than 1 granular or epithelial cast per low-power field was found. The findings for the presence and the extent of both d-RBC and casts were in good accord with and changed with the clinical course, indicating that d-RBC and casts of urinary sediment can be used to predict the prognosis of patients with renal disease. PMID- 1507491 TI - [Urinary cytology for carcinoma of the urinary bladder]. AB - Cytologic examinations of voided urine were reviewed for 82 cases of invasive or noninvasive papillary carcinoma and 25 cases of carcinoma in situ of the urinary bladder. Five of the 82 cases of invasive or noninvasive papillary carcinoma and 3 of the 25 cases of carcinoma in situ were asymptomatic, and malignancy was detected only by urinary cytology. Urinary cytology was positive in 18.5% of the Grade 1, 33.3% of the Grade 2, 75% of the Grade 3 noninvasive carcinomas and in 77.8% of the invasive carcinomas. However, all 25 cases of carcinoma in situ gave positive cytologic results. Malignant cells found in Grade 1 noninvasive papillary carcinoma were slightly atypic in shape. Their nuclei were small but showed mild to moderate hyperchromasia. These malignant cells appeared in small clusters but the number of clusters were few. In Grade 2 or 3 noninvasive papillary carcinoma, malignant cells appeared in small clusters or isolated single cells. Their nuclei were irregular in shape and showed moderate to marked hyperchromasia. In invasive carcinoma and carcinoma in situ, many malignant cells with marked atypia were observed, but in carcinoma in situ, the background of the specimens was clean. PMID- 1507492 TI - [Pathophysiological analysis of diabetes mellitus and complications from the urine of diabetic patients]. AB - Of the many information obtainable from the urine of diabetic patients, urinary C peptide (CPR), albumin and anti-diuretic hormone (ADH) were representatively described using my clinical and experimental data. C-peptide excretion in 24h collection of urine is a good estimate of insulin secretion from the pancreas and thus low in IDDM patients and even in NIDDM patients at a later stage, but high in pathological conditions including Graves' disease, obesity, liver cirrhosis and Cushing's syndrome. Urinary albumin excretion in small amounts (microalbuminuria) is usually observed in diabetic patients who have been under a poor control state of diabetic hyperglycemia for over 5 years and provides a good tool for monitoring early diabetic nephropathy. The grade of microalbuminuria (30 300 mg/day) is positively correlated with the HbA1 level in diabetic patients, showing that microalbuminuria is reversible along with an improvement of diabetic control at least in an early phase of diabetic nephropathy. As the albumin level measured in a spot urine sample correlates well with the value in the 24h collection of urine, the albumin measurement is conveniently feasible with a spot urine sample at every patient's visit. The amount of ADH excreted in urine is 7 10% of that secreted from the posterior pituitary. The excretion of ADH in a day was in the urine of diabetic patients positively correlated with HbA1, urinary osmolarity and concentration of sodium in urine, although the pathological meaning of the observed ADH hypersecretion in the development of diabetic complications is currently unknown. PMID- 1507493 TI - [Quantitative analysis of urinary organic acid]. AB - We showed the optimum conditions for analysis of urinary organic acids using solvent extraction and GC/MS by the stable isotope dilution technique. Examples of the diagnosis in a case of heterozygote of ornithine transcarbamylase deficiency and a case of multiple carboxylase deficiency were described. The accurate quantitative analysis of urinary organic acids with stable isotope dilution technique is necessary for routine examination conducted in clinical laboratories. PMID- 1507494 TI - [Urinary trypsin inhibitor as an acute phase reactant]. AB - Early in this century, trypsin inhibiting activity has already been recognized in patients with acute infection or renal disease. In addition to these, conditions such as coronary thrombosis, surgical operation, artificial fever by heat-killed bacilli, malignancy, leukemia, later stage of normal pregnancy, etc. have been known to cause the elevated excretion of UTI in urine. Typically, maximal excretion of UTI has been observed within one or two days after the onset. It appears that recent studies have overcome the complexity of UTI molecule. Automated measurement of urinary trypsin inhibitor (UTI) in urine sample was carried out by either enzymic or immunologic method. UTI as well as erythrocyte sedimentation rate and C-reactive protein enables us to monitor acute phase response, being confirmed in cases of abdominal surgery. PMID- 1507495 TI - [Immunophenotypic and immunogenotypic analyses of acute leukemia and lymphoblastic lymphoma expressing myeloid and lymphoid antigens]. AB - By using monoclonal antibodies against lymphoid and myeloid differentiation antigens, surface marker analysis was performed on the tumor cells from 42 patients with acute leukemia and lymphoblastic lymphoma. Nine (21%) of 42 cases were diagnosed biphenotypic leukemia. Two (17%) of the 12 patients with acute myeloid leukemia, four (18%) of 22 with acute lymphocytic leukemia and three (38%) of 8 with lymphoblastic lymphoma expressed both lymphoid and myeloid antigens. Tumor cells from six patients expressed both T-cell and myeloid antigens, and those from three other expressed both B-cell and myeloid antigens. Southern blot analysis was performed on the DNA from four patients with biphenotypic leukemia cells expressing T-cell and myeloid antigens. DNA from one patient showed clonal rearrangement of the immunoglobulin heavy chain (IgH) gene, and that from one other showed clonal rearrangement of both IgH gene and T-cell receptor beta-chain gene. DNA from two other patients showed a germline configuration of both genes. These results indicate that biphenotypic leukemia, especially T-cell and myeloid phenotype, is not so rare in acute leukemia and lymphoblastic lymphoma. The results of immunogenotypic analysis were not consistent with those of immunophenotypic analysis in biphenotypic leukemia. PMID- 1507496 TI - [A method for determination of proinsulin levels in serum using both insolubilized anti-insulin antibody and anti-C-peptide antibody]. AB - A method is described for determination of proinsulin levels in serum. The principle of the assay is that proinsulin reacts with both anti-insulin and anti C-peptide antibodies. The assay procedure is as follows; Anti-insulin antibody fixed to bacterial cell wall and insolubilized is incubated with test serum to form a complex of proinsulin-anti-insulin antibody (solid phase), followed by washing twice with buffer to eliminate free C-peptide. Then, glycin-HCl buffer is added to dissociate the bound proinsulin. After centrifugation, the supernatant is neutralized with NaOH and proinsulin in it is measured using RIA kit for CPR assay. The assay is simple, sensitive and reproducible. Neither insulin nor C peptide contained in test serum influences the proinsulin levels determined by this assay. The mean +/- S.D. of the fasting serum proinsulin levels of healthy donors was 7.0 +/- 2.6 PM/l. A patient with insulinoma showed extremely high serum proinsulin level, which decreased to the normal range after extirpation of insulinoma. PMID- 1507497 TI - [Evaluation of serum troponin T measurement in acute myocardial infarction]. AB - A monoclonal solid phase enzyme immunoassay has been developed for the detection of human troponin T. The serum troponin T levels in healthy subjects gave 0.05 +/ 0.06 ng/ml in total (n = 176), 0.06 +/- 0.07 ng/ml in males (n = 79) and 0.03 +/ 0.05 ng/ml in females. Within-run and between-run precision (CVs) of the assay were less than 5%. Various common interferents tested did not affect on the assay, but higher titer of rheumatoid factor, and anti-coagulants such as EDTA, heparin oxalate and citrate affected the assay. In all patients with defined acute myocardial infarction, serum troponin T levels increased 7 to 10 folds the upper reference range within 6 hours after the onset of chest pains and maximum elevation of serum troponin T level was at around 20 hours and its levels remained elevated for 7 to 20 days. Specificity and sensitivity for acute myocardial infarction was 92.4% and 100%, respectively. The results indicated that troponin T measurement improved the diagnostic efficiency for the detection of myocardial necrosis as compared with conventionally used cardiac enzymes and was an effective tool for the confirmation of the reperfusion by PTCA and PTCR. PMID- 1507498 TI - [Study on changes of serum vitamin K1 level and K dependent coagulation factors in patients with coumarin derivatives (warfarin) therapy]. AB - Serum level of vitamin K1 (= phylloquinone, hereinafter K1) and K dependent blood coagulation factors were determined by HPLC in normal subject, liver cirrhosis, hepatocellular carcinoma, acute hepatitis, chronic hepatitis, chronic renal failure with hemodialysis and patients under warfarin therapy. Normal range of serum K1 concentration was decided on 0.20-2.30 (0.87 +/- 0.53, n = 96) ng/ml. Serum K1 level showed no significant differences among normal subject, various diseases and warfarin therapy. Correlation between serum K1 level and F-VII (r = 0.879, p less than 0.001) or protein C activity (r = 0.839, p less than 0.01) was found in patients whose thrombotest was 20% and less. However serum K1 level didn't correlate with any K dependent coagulation factors in patients if thrombotest was over 20%. PMID- 1507499 TI - [Differentiation of fibrinolysis and fibrinogenolysis by analysis of FDP fragments]. AB - We previously analysed the fragments of fibrin/fibrinogen degradation products (FDP) by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) combined with immunoblotting. In this report, we studied the semi-quantitative analysis of fibrinolysis (degradation of cross-linked fibrin) and fibrinogenolysis (degradation of fibrinogen and/or unstable fibrin) of patients' samples by our method. In vitro study of FDP made it clear that an appearance of D fragment confirmed fibrinogenolysis and an appearance of DD fragment and/or high molecular weight fragments which have higher molecular weight than DY or X fragment confirmed fibrinolysis. In addition, a study with mixtures of various concentrations of fibrin degradation products (FbDP) and fibrinogen degradation products (FgDP) demonstrated a dose dependent intensity of band by immunoblot method. These results show that our method is favorable for the semi-quantitative analysis of fibrinolysis and fibrinogenolysis. We applied the method to 6 samples from patients with disseminated intravascular coagulation (DIC). Consequently, fibrinogenolysis was observed in all of 6 samples, in which fibrinogenolysis was more enhanced than fibrinolysis in one sample, and an equivalent degree of fibrinolysis and fibrinogenolysis were observed in 3 of 6 samples. Although our method was probably devoid of the ability to distinguish FgDP from degradation products of unstable fibrin, these findings indicate that fibrinogenolysis is, at any rate, enhanced in the majority of patients with DIC, besides fibrinolysis. PMID- 1507501 TI - [The nutrition of the aged]. PMID- 1507500 TI - [Immunohistochemical study of EGF and EGF-R on the esophageal carcinomas--from a standpoint of depth of invasion]. AB - We performed immunohistochemical stainings for epidermal growth factor (EGF) and epidermal growth factor receptor (EGF-R) on 63 resected esophageal carcinomas without preoperative treatment and 12 cases with preoperative radiation to clarify a relationship between positivity and depth of invasion. EGF and EGF-R showed a similar positivity (75% of early cases and 88.9% of advanced ones invaded beyond submucosa). In advanced carcinomas, the positivity in each layer was 75% in the mucosa, 86.7% in the submucosa and muscle layer, and 93.3% in the adventitia. All lesions of nodal metastases were positive for these stainings. Sixty % of cases with preoperative radiation were positive. The degenerated cells showed weak positivity. However, the viable cells showed similar positivity to those of non-treated cases. PMID- 1507502 TI - [Decrease of male sexual activity by aging]. PMID- 1507503 TI - [Sexual behavior in elderly females]. PMID- 1507504 TI - Gerontological education in Japan--in training of social welfare personnel and nurses. AB - Though Japan is noted for the custom of respect for the elderly, gerontological education is not widely practiced. At present it is only done in the training of several professionals and semi-professionals in health and welfare services for the elderly, i.e., medical doctors, nurses, social workers, and care workers for the disabled and older persons. In the training of social workers who are expected to serve as the pivot of a team for psycho-social help and caregiving, gerontological education is given as a part of social work education. In schools for care workers for the disabled and older persons that are two-year vocational schools, practical gerontological knowledge and skills needed in the care of the elderly are taught as an important base for their future work. In schools of nursing, most of which are two-year or three-year vocational schools in Japan, gerontological education is included as an indispensable component of the curriculum and is being given increasing importance these days. PMID- 1507505 TI - Gerontological education in Japan--geriatric education and training. AB - There are 13 academic geriatric departments among 80 medical schools in Japan as of November 1991. The first independent department was established in 1962 at Tokyo University. The undergraduate education program includes lectures in geriatrics (20 hours/year in 11/12 medical schools), bedside teaching at geriatric ward (6/12 medical schools, 66 hours on average per year). The theme of lectures are diverse and incorporate all the three major fields in gerontology: biology of aging, clinical geriatrics and socio-economical aspects of aging society. The postgraduate geriatric education is carried out mainly at university setting and most of the medical schools (83%) accept graduate students who are trained at independent geriatric ward (92%) as well as at outpatient clinics. In 1989, Japan Geriatrics Society started a new certification system by which 687 MDs have been temporarily certified in geriatrics. The first examination will be given by the society in 1992 and the eligibility to sit in the examination requires three years geriatrics fellowship after certification in medicine or general surgery. The curriculum proposed by the society shares many items of training in common with those found in north American and in Europe. Some points of suggestions and recommendations were presented for future improvement in the education of gerontology in Japan. PMID- 1507506 TI - International comparison in gerontological education--Canada. AB - The undergraduate programs of geriatric education in medical schools across Canada are variable, and there has not been definition of core content or core clinical experience, although these processes are underway. At UBC in June 1990, the first Canadian Summer Institute took place in Vancouver and medical students representing 16 medical schools in Canada attended the week-long program. Students left the program keen to start student interest groups in their schools. Many students were indicating commitment to careers in geriatrics, both clinical and research. There is a Certificate of Special competence by examination in Canada, administered by the Royal College of Physicians and Surgeons of Canada. The standards for the program have been in place since 1981, and since 1984 candidates for the examination must have a minimum of two years training in Geriatric Medicine after at least three years training in Internal Medicine. To date, there are less than 75 certified Specialists in Geriatric Medicine in the country. The College of Family Physicians of Canada encourages training in care of the elderly during the two-year training program in Family Practice. In some schools (e.g. UBC) at least one month is mandatory. There is a Joint Committee with representatives from the Royal College and the College of Family Physicians making recommendations for geriatric training in Family Practice programs in Canada. The College of Family Practice has elected not to have a program for certification in geriatrics for family physicians. Gerontology and geriatrics are being incorporated into undergraduate and graduate curriculae, driven by the demographic imperative. There remains much to be done.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1507507 TI - Gerontological education in Australia. AB - Courses in Gerontology and Geriatric medicine are now provided in most undergraduate training programs for medical, allied health and social work professionals in Australian Universities. The depth and coverage varies between schools but almost all undergraduate social workers, nurses, medical practitioners and allied health professionals will receive some training and in several cases more extensive optional programs are offered. PMID- 1507508 TI - Training in geriatric medicine in United Kingdom. PMID- 1507509 TI - The growth of gerontology & geriatrics in the United States. AB - Since the confirmation of the Older American's Act (OAA) in 1965, the growth of gerontology and geriatrics, has literally come of age in the United States. Although individual aging courses were offered in higher education prior to passage of the OAA, few gerontology programs had been established. On campuses where gerontology courses were available, they represented electives connected with a pre-existing discipline, such as social work or family studies. However, 1965 was a watershed year for gerontology instruction since it heralded the provision of federal funding support, beginning with that of the Administration on Aging (AoA), to help develop, pilot, and oversee gerontological programs in American institutions of higher learning. Initially, instruction was at an undergraduate level, but later gerontology degree programs were established at the master's level, with the first gerontology degree program originating at North Texas State University, in 1967. This program was followed a year later (1968) by a program at the University of South Florida. While funding from AoA began in 1966, funding from other federal agencies (e.g., the Bureau of Health Professions (BHP); the National Institute on Aging (NIA); the National Institute of Mental Health (NIMH), Mental Disorders of Aging Branch; and the Veteran's Administration (VA))--the five agencies that became the basis for a 1984 and 1987 Report on Education and Training in Geriatrics and Gerontology,--did not begin until the mid 1970s. The mid 1970s reflected the growing awareness of the demographic shift in America and around the world, particularly in developed nations.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1507510 TI - [Acute hemodynamic effects of intravenous bolus injection of isosorbide dinitrate in aged patients with congestive heart failure]. AB - In order to investigate whether intravenous bolus injection of isosorbide dinitrate (ISDN) is a safe and efficient therapy in aged patients with congestive heart failure, we studied acute hemodynamic effects in 11 patients. Peak effects on preload were observed after 5 to 10 minutes of bolus injection and unloading effects continued effectively for 60 minutes. At peak effect, pulmonary systolic pressure decreased from 50.2 +/- 2.6 to 36.2 +/- 2.6 mmHg (-28.5%, p less than 0.01) and pulmonary end diastolic pressure decreased from 25.0 +/- 2.2 to 18.5 +/ 2.1 mmHg (-26.0%, p less than 0.01). Mean pulmonary artery wedge pressure decreased from 23.4 +/- 2.2 to 16.0 +/- 2.1 mmHg (-31.6%, p less than 0.01). Mean right atrial pressure decreased from 10.5 +/- 1.8 to 7.4 +/- 2.0 mmHg (-29.5%, p less than 0.01). Blood pressure, heart rate, cardiac index, systemic and pulmonary vascular resistance showed no significant changes. Thus, intravenous bolus injection of ISDN showed a potent vasodilator effects on preload, and may be a safe and useful treatment for aged patients with acute congestive heart failure. PMID- 1507511 TI - [Clinical significance of measuring glycated fibrinogen in plasma in diabetes mellitus]. AB - The clinical significance of measuring glycated fibrinogen (G Fbg) in plasma was studied using a simple, rapid method for determining plasma G Fbg developed by the authors. This method is based on modified fibrin clot formation for purification of plasma Fbg, and G Fbg was estimated by improved colorimetric fructosamine assay. The values of plasma G Fbg were expressed as glycated polylysine equivalents (mumol/l). In this clinical study, 106 examinees who underwent a screening test for diabetes mellitus (DM) because of glycosuria or hyperglycemia were investigated. According to the WHO diagnostic criteria, they were divided into 3 groups: non DM group (n = 35), impaired glucose tolerance (IGT) group (n = 31) and DM (non-treated) group (n = 40). In addition, healthy controls (n = 40) and treated diabetic patients (DM treated) were involved. Plasma G Fbg/Fbg, fasting plasma glucose (FPG), fructosamine and glycated hemoglobin (HbA1c) were also analyzed in subjects of the 5 groups. Non-treated DM patients showed high levels of plasma G Fbg, which were significantly higher than those of any other groups. G Fbg levels in IGT group were significantly higher than those in healthy controls or the non-DM group. Together with a significant positive correlation between G Fbg and FPG, these results indicate that the levels of plasma G Fbg depend on plasma glucose levels.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1507512 TI - [The relation between bone calcium metabolism and senile aortic valve calcification]. AB - The authors assessed the affect of bone calcium metabolism on aortic valve calcification (AVC) in 189 septua- and octogenarians (49 males and 140 females, 81.0 +/- 4.4 yrs). Both AVC and mitral annular calcification (MAC) were evaluated by two-dimensional echocardiography, and then the degree of AVC was classified into three categories; C-1: calcification seen in one cusp of the aortic valve, C 2: calcification in two cusps, and C-3: calcification in three cusps. Bone mineral content (BMC) of three lumbar vertebral bodies was obtained by quantitative computed tomography using a calibrated phantom. Serum calcium, phosphate, parathyroid hormone, calcitonin, and osteocalcin were also examined within a month. The patients were classified into age-matched five groups in both sexes; Group-C: MAC (-) and AVC (-) (n = 79); Group-A1: MAC (-) and AVC (+) with C-1 (n = 35); Group-A2: MAC (-) and AVC (+) with C-2 (n = 19); Group-A3: MAC (-) and AVC (+) with C-3 (n = 15); and Group-AM: MAC (+) and AVC (+) in any cusp (n = 42). In males, BMC decreased in the order of Groups-A3 (83 +/- 27 mg/cm3), -C (67 +/- 50), -AM (62 +/- 62), -A2 (61 +/- 38), and -A1 (59 +/- 58), but there was no significant difference between any of the five groups. In females, the BMC in Group-AM (29 +/- 24) was significantly less than that in Group-C (48 +/- 35) (p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1507513 TI - [Bactericidal clothes protect against respiratory infections in the elderly patients]. AB - In order to protect against infections in the elderly patients, bactericidal clothes were used. Ninety elderly patients were divided into two groups; the control group and the other group with bactericidal clothes. In period I neither group received particular treatment for three months and in period II only the treated group used bactericidal clothes for three months. The control group in period II used regular clothes throughout. Cause of fever (greater than 37 degrees C) extending more than 10 or 15 days were significantly lower in the treated group than in the control group. It was suggested that the bactericidal clothes reduce infections in elderly patients. PMID- 1507514 TI - [An autopsy case of endocardial cushion defect (ECD) in an 82-year-old female]. AB - In an 82-year-old female case of endocardial cushion defect (ECD), a systolic regurgitant murmur was heard at the apex, and her ECG showed atrial fibrillation without right bundle branch block or left axis deviation. An echocardiogram demonstrated atrial septal defect (ASD) and a cleft of the anterior mitral leaflet with calcification. She died of refractory congestive heart failure. Autopsy revealed ECD (intermediate type) with mitral and tricuspid cleft, and ASD (ostium primum type, 2.0 x 1.0 cm in diameter). In addition, mitral ring calcification and calcification of the cleft mitral valve was disclosed, causing mitral stenosis in addition to mitral regurgitation due to the cleft mitral valve. This was the second oldest Japanese autopsy case of ECD. We concluded that echocardiographic examinations, including color flow imaging, in aged patients with heart murmur are necessary to confirm the diagnosis of congenital heart disease in the aged. PMID- 1507515 TI - [Statistical analysis of post-stroke patients in a rehabilitation institution (the second report)]. PMID- 1507516 TI - [A case of cerebral infarction associated with a superficial punctate keratitis and corneal abrasion due to amantadine hydrochloride]. PMID- 1507517 TI - Antiarrhythmic effects of MS-551, a new class III antiarrhythmic agent, on canine models of ventricular arrhythmia. AB - The antiarrhythmic effects of MS-551, which prolongs cardiac action potential duration without affecting the maximum upstroke velocity of the action potential, were assessed in three different canine ventricular arrhythmia models: 1) ventricular tachycardia (VT) induced by electrical stimuli 3-5 days after myocardial infarction, 2) spontaneous ventricular tachyarrhythmias 24-48 hr after two-stage coronary ligation and 3) ventricular tachyarrhythmias induced by digitalis. Intravenous administration of MS-551 (0.1-1 mg/kg) decreased the susceptibility in 10 dogs out of 13 to VT or ventricular fibrillation evoked by programmed electrical stimulation (PES) delivered to the ventricular septum 3-5 days after myocardial infarction. Oral administration of MS-551 (3 mg/kg) also decreased the susceptibility to VT evoked by PES in 7 out of 10 conscious postinfarction dogs. Concurrently, intravenous (0.1-1 mg/kg) or oral (3 mg/kg) administration of MS-551 produced increases in the ventricular effective refractory periods (ERP) by 7 +/- 1% - 17 +/- 3% or 13 +/- 2%, respectively. Similarly, d-sotalol (0.3-3 mg/kg, i.v. and 10 mg/kg, p.o.) decreased the susceptibility to VT with increased ERP. However, MS-551 (1 and 10 mg/kg, i.v.) failed to inhibit both canine two-stage coronary ligation arrhythmia and digitalis arrhythmia. These results suggest that MS-551 is a pure class III antiarrhythmic drug which may be effective in the treatment of life-threatening reentrant tachyarrhythmias, but not in automaticity arrhythmias. PMID- 1507518 TI - Effect of nebracetam on the disruption of spatial cognition in rats. AB - Central cholinergic hypofunction causes the disruption of spatial cognition, while cholinomimetics improve this disruption in rats. Scopolamine (0.5 mg/kg, i.p.) has also been reported to disrupt radial maze performance in rats. Nebracetam (WEB 1881 FU), a new nootropic candidate, was able to correct this scopolamine-induced disruption of spatial cognition at the dose of 10 mg/kg, p.o. Furthermore, nebracetam enhanced oxotremorine-induced tremors in mice. These results indicate that nebracetam has a cholinergic enhancing effect. The scopolamine-induced disruption of spatial cognition has been previously reported to improve not only by cholinomimetics but also by brain noradrenergic drugs such as L-threo-DOPS and amantadine. Nebracetam reversed the change of brain noradrenaline contents in the frontal cortex and hippocampus in which the noradrenaline content decreased by treatment with scopolamine. Nebracetam also decreased the delta 9-tetrahydrocannabinol (6 mg/kg, i.p.)-induced disruption of spatial cognition, which was reported to be related to the lymbic noradrenergic function. These results suggest that the cognitive enhancing effect of nebracetam involves not only cholinergic mechanisms but also involves lymbic and hippocampal noradrenergic mechanisms. PMID- 1507519 TI - The effects of oxiracetam (CT-848) on local cerebral glucose utilization after focal cerebral ischemia in rats. AB - The effects of oxiracetam on the reduction of brain metabolism induced by focal cerebral ischemia were investigated by measuring local cerebral glucose utilization (LCGU) in rats 24 hr after left middle cerebral artery occlusion. Focal cerebral ischemia reduced LCGU in the entire ipsilateral cortex, the greatest reduction being in the lateral parts of the frontoparietal cortex. LCGU was slightly reduced in the contralateral cortex; this reduction was considered to be caused by diaschisis. Oxiracetam was administered intraperitoneally for 3 days prior to middle cerebral artery occlusion. In the ipsilateral cortex, LCGU reduction was minimized in the ischemic center areas by oxiracetam at a dose of 400 mg/kg and in more extensive areas, by a dose of 800 mg/kg. Moreover, oxiracetam at a dose of 800 mg/kg enhanced metabolism impaired by diaschisis in the caudal areas of the contralateral cortex. These findings suggest that oxiracetam minimizes the reduction of brain function induced by ischemia and may therefore be useful in the treatment of cerebrovascular disease. PMID- 1507520 TI - Effect of L-NG-nitro-arginine, inhibitor of nitric oxide synthesis, on autoregulation of renal blood flow in dogs. AB - The present experiments were designed to evaluate the importance of nitric oxide in the regulation of renal hemodynamics and the autoregulation of renal blood flow (RBF) in anesthetized dogs. RBF was measured by an electromagnetic flowmeter, and renal arterial pressure (RAP) was varied by an adjustable aortic clamp. The RAP-RBF relations were examined during the intrarenal infusion of saline or agents. The intrarenal infusion of L-NG-nitro-arginine (L-NNA, 40 micrograms/kg.min) at normal RAP decreased RBF and urine flow (UF), while the infusion of L-arginine.HCI (1 mg/kg.min) increased RBF and UF. Both agents did not affect the glomerular filtration rate and mean arterial pressure. The autoregulation of RBF was impaired during the L-NNA infusion. The L-arginine infusion did not affect autoregulatory efficiency. When L-NNA (40 micrograms/kg.min) and L-arginine were infused simultaneously into the renal artery, the autoregulation of RBF was maintained. However, a higher dose of L-NNA (200 micrograms/kg.min) impaired the autoregulation of RBF. These results suggest that the basal production and/or the release of nitric oxide contributes to the regulation of renal hemodynamics and urine formation. During the reduction of RAP, nitric oxide may play an important role in the autoregulation of RBF. PMID- 1507521 TI - Effects of sulfhydryl-related compounds on indomethacin-induced gastric lesions in rats: role of endogenous sulfhydryls in the pathogenesis. AB - The role of mucosal sulfhydryl (SH) in the pathogenesis of indomethacin-induced gastric lesions was investigated in rats. Indomethacin (25 mg/kg, s.c.) caused high-amplitude gastric contractions, resulting in linear hemorrhagic lesions in the corpus mucosa within 4 hr, but did not induce any changes in the mucosal SH levels. These lesions were prevented significantly by prior s.c. administration of cysteamine, glutathione (GSH) or diethylmaleate (DEM), irrespective of whether the mucosal SH was increased by the former two agents or reduced by the latter. N Ethylmaleimide (NEM) tended to worsen such lesions without any effect on the mucosal SH contents. Gastric hypermotility caused by indomethacin was inhibited significantly by DEM, cysteamine and GSH, while acid secretion was reduced by DEM and NEM. Both cysteamine and GSH prevented the indomethacin-induced linear lesions even in the stomach perfused with 150 mM HCl, whereas in the animals treated with DEM, nonlinear damage was induced exclusively in the antrum by indomethacin in the presence of acid. We conclude that the mucosal SH has no relation to the ulcerogenicity of indomethacin in the gastric corpus mucosa. PMID- 1507522 TI - Consecutive treatment of disulfiram inhibits ovarian carbonyl reductase activity in rats. AB - We investigated the effects of disulfiram (DS) on ovarian carbonyl reductase activity in rats to determine the influence of DS on female reproductive function. Three consecutive treatments with DS significantly inhibited ovarian carbonyl reductase activity as well as ovulation, dose-dependently. Single treatment with DS had no effect on ovarian carbonyl reductase activity. Our observations indicate that consecutive treatment with DS has an inhibitory action on female reproductive function, although DS is well-known to inhibit aldehyde dehydrogenase and dopamine beta-hydroxylase. PMID- 1507523 TI - Working and reference memory in rats in the three-panel runway task following dorsal hippocampal lesions. AB - Using a three-panel runway task, the influence of dorsal hippocampal lesions on working and reference memory in rats was investigated. Despite 20 postoperative training sessions, rats with hippocampal lesions were unable to perform the working memory task. In the acquisition process of the reference memory task, however, there was no significant difference between hippocampal- and sham lesioned rats. On the other hand, rats trained preoperatively with a working memory procedure, and then subjected to hippocampal lesions, showed more errors (pushes made on the two incorrect panels of the three panel-gates located at four choice points) than did sham-lesioned rats. The increase in working errors induced by hippocampal lesions was not reduced during 10 subsequent re-training sessions. Hippocampal lesions had no effect on retention of the reference memory performance. The increase in working errors in hippocampal-lesioned rats was significantly reduced by treatment with the cholinesterase inhibitor physostigmine at 0.1 mg/kg and the cholinergic activating drug minaprine at 10 mg/kg. These findings suggest that lesions of the dorsal hippocampus selectively impair the ability to carry out the working memory task whether rats are trained preoperatively or postoperatively, and that the working memory loss in hippocampal-lesioned rats is mediated by lowering of the cholinergic function. PMID- 1507524 TI - Accelerating action of quinidine on the decay phase of transient outward current in dissociated hippocampal pyramidal neurons of rats. AB - The effect of quinidine on the transient outward current (IA) in rat hippocampal neurons was studied. Quinidine at 1 x 10(-6) M or more dose-dependently decreased the IA without affecting the current-voltage relationship. Quinidine accelerated the decay phase of the IA, suggesting the blockade of open channels. This result may have an implication on the side effects of quinidine in the central nervous system, since the IA is involved in the control of rhythmic electrical activity of the neurons. PMID- 1507525 TI - Agonistic-antagonistic actions of clomiphene citrate on PGF2 alpha fluctuations in ovariectomized rat uterus. AB - Effects of clomiphene and/or estrogen on uterine prostaglandin (PG) F2 alpha fluctuations in ovariectomized rats were examined. Uterine PGF2 alpha fluctuations were measured at the indicated times after injection of clomiphene and/or estradiol. Antiestrogenic effects of clomiphene on urine weight and PGF2 alpha levels were observed at 6 hr, and its effect on uterine 13,14-dihydro-15 keto-PGF2 alpha forming capacity was observed at 24 hr. At 48 and 72 hr, additive effects were recognized in all parameters. These results indicate that clomiphene possesses agonistic-antagonistic actions on the PGF2 alpha fluctuations in the uterus. PMID- 1507526 TI - Molecular orbital studies on the structure-activity relationships of catechol O methyltransferase inhibitors. AB - Quantum chemical studies were applied to analyze the activities of catechol O methyltransferase (COMT) inhibitors. Molecular orbital calculations of inhibitor molecules were made by semi-empirical molecular orbital calculations, CNDO/2 (complete neglect of differential overlap) methods. Regression analysis among theoretical reaction indices based on the frontier electron theory and COMT inhibitory activities were carried out. The COMT inhibitory actions of two series of inhibitors, a series of 1,5-substituted 3,4-dihydroxy benzenes and a series of substituted 3-hydroxy-4-methoxy benzenes, were investigated. The resulting regression equations contain two common reaction indices as regression variables: the electron density on the oxygen atom of the hydroxyl group and the super delocalizability on the 5th carbon atom of the benzene ring. These two atomic positions are considered to play an important role in the interaction of these inhibitors with COMT. The hydroxyl of atomic position 3 is probably indispensable to the COMT inhibitory action by these inhibitors. PMID- 1507527 TI - Advance in smooth muscle electrophysiology. PMID- 1507528 TI - Regulation of vascular smooth muscle contractility: roles of the sarcoplasmic reticulum (SR) and the sodium/calcium exchanger. PMID- 1507529 TI - Ca(2+)-compartments in smooth-muscle cells. PMID- 1507530 TI - Multiple angiotensin receptors: selective ligands and functional correlates. PMID- 1507531 TI - Spatiotemporal aspects of calcium signalling. PMID- 1507532 TI - Myosin light chain kinase: structure-function relationships. PMID- 1507534 TI - ATP-gated cation channels in vascular smooth muscle cells. PMID- 1507533 TI - Neural and metabolic control of arteriolar diameter. AB - During sympathetic nerve activity, sympathetic transmitter causes depolarizations which trigger voltage dependent Ca++ entry. The ability of arteriolar membranes to sum together successive e.j.ps is changed as a consequence of cellular activity, i.e. increased [K+]o. Furthermore, the ability of arteriolar membrane to permit voltage dependent Ca++ entry is modified by a second consequence of cellular activity, i.e. changes in external pH. PMID- 1507535 TI - Comparison of nitric oxide, S-nitrosocysteine and EDRF as relaxants of rabbit aorta. PMID- 1507536 TI - The regulatory functions of the endothelium. PMID- 1507537 TI - Identification of a specific binding site for K+ channel openers in rat aorta. AB - The K+ channel openers (KCOs) form a structurally heterogeneous group of compounds which relax smooth muscle by opening K+ channels in the plasmalemma. At present it is not known whether these drugs open the same K+ channel in smooth muscle and, if so, whether they bind to the same site of this channel. To address these questions we present the first binding study with KCOs in a smooth muscle preparation. In intact rat aortic strips, the novel tritiated KCO, 3H-P1075 (N cyano-N'-(1,1-dimethyl[2,2,3,3(3)H]propyl)-N"-3-pyridylguanidine++ +), a potent pinacidil analogue, showed saturable specific binding of high affinity (KD = 6 +/ 1 nM, Bmax = 23 +/- 3 fmol/mg tissue wet weight). Specific binding of 3H-P1075 was inhibited stereospecifically by representatives from all major families of K+ channel openers, with a rank order of potency that correlated well with the potencies for vasorelaxation in rat aorta. The sulfonylurea glibenclamide, a relatively specific blocker of ATP-sensitive K+ channels and an inhibitor of the effects of KCOs, also inhibited 3H-P1075 binding and increased the rate of dissociation of 3H-P1075 from the tissue in a concentration-dependent manner. Lowering temperature (from 37 degrees C to 2 degrees C) and decreasing intracellular ATP levels by metabolic poisoning, diminished specific 3H-P1075 binding by reducing Bmax. However, depolarization (KCl = 55 mM) or lowering pH from 7.4 to 6.0 did not influence binding. The data demonstrate the existence of a specific binding site for the KCO 3H-P10756 in rat isolated aorta, which seems to be of functional relevance.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1507538 TI - Modulation of myosin phosphorylation-contraction coupling in skinned smooth muscle. PMID- 1507539 TI - Potassium channel openers: effects on the vascular system. PMID- 1507540 TI - Regulation of arterial tone by potassium channels. PMID- 1507541 TI - Selective of Ca channels modulators in smooth muscle. PMID- 1507542 TI - Identification of the sites and effects of phosphorylation of smooth muscle calponin by protein kinase C. PMID- 1507543 TI - Calponin in bovine aorta smooth muscle. PMID- 1507544 TI - Interaction between the heavy chain (HC) and the regulatory light chain (RLC) in smooth muscle myosin subfragment-1 (S-1). PMID- 1507545 TI - Determination of the conformational change on smooth muscle myosin molecule caused by phosphorylation with hydrodynamical analysis. PMID- 1507546 TI - Vascular relaxing mechanism of denopamine in isolated canine coronary, femoral, mesenteric and renal arteries. PMID- 1507547 TI - Reassessment of noradrenergic function in salt-induced hypertension in Dahl rats. PMID- 1507548 TI - Temporal changes in the Ca(2+)-force relationship during norepinephrine-, serotonin- and high K(+)-induced contractions in the rabbit femoral artery. PMID- 1507549 TI - Effects of a novel endothelin antagonist, BQ-153, on endothelin-induced vasoconstriction in porcine blood vessels. PMID- 1507550 TI - Plasma concentration of and pulmonary vascular response to endothelin-1 in rats with pulmonary hypertension. PMID- 1507552 TI - Vasoconstrictor mechanism of endothelin-1 probably differs between canine systemic resistance and capacitance vessels. PMID- 1507551 TI - Potentiation by endothelin-1 of 5-hydroxytryptamine-induced contraction in coronary artery of the pig. PMID- 1507553 TI - Endothelin induces Ca(2+)-transients in endothelial cells in situ. PMID- 1507554 TI - Enhanced reactivity to endothelin in reperfused coronary arteries. PMID- 1507555 TI - Potential mechanism of contractile activation by U46619 in rabbit aorta. PMID- 1507556 TI - Eicosapentaenoic acid suppressed the proliferation of vascular smooth muscle cells through modulation of binding of growth factor. PMID- 1507557 TI - Enhancement of PGI2 formation by eicosapentaenoic acid in rat vascular smooth muscle cells: possible involvement of lipid peroxides. PMID- 1507558 TI - Anti-proliferative effect of prostaglandins A and J on cultured vascular smooth muscle cells. PMID- 1507559 TI - Mechanical effects of 16-methyl analogues of PGE2 on the circular and longitudinal muscles of the guinea-pig isolated colon. PMID- 1507560 TI - Involvement of chloride-bicarbonate exchange in cell volume regulation during potassium contracture of single isolated smooth muscle cells. PMID- 1507561 TI - Bronchodilatory activities of 1,3,7-trialkylxanthine derivatives. PMID- 1507562 TI - Inhibitory effect of 2,3-dibenzylbutane-1,4-diol, a mammalian lignan, on contraction induced by norepinephrine in rat aorta. PMID- 1507563 TI - Effects of L-nitroarginine on the non-adrenergic, non-cholinergic i.j.p. and relaxation of rat stomach. PMID- 1507564 TI - An embryological aspect of cholinergic innervation in the cardiovascular system. PMID- 1507565 TI - Effects of tachykinins and guanethidine on the acetylcholine output stimulated by nicotine from guinea-pig bladder. PMID- 1507566 TI - Release of endogenous adenyl purines from rabbit ear artery. PMID- 1507567 TI - Hepatic ischemia-reperfusion injury to the cardiovascular system in rats. PMID- 1507568 TI - Underlying mechanisms for hypoxia-induced relaxation of the guinea-pig isolated aorta. PMID- 1507569 TI - Hypoxia-evoked dilatation of rabbit isolated basilar arteries is not mediated by the opening of glibenclamide-sensitive potassium channels. PMID- 1507570 TI - The mechanism of vasoconstriction induced by oxygen-derived free radicals in rat aorta. PMID- 1507571 TI - Time-course analysis of the mechanical properties of the canine basilar artery subjected to experimental subarachnoid hemorrhage. PMID- 1507572 TI - Heterogeneity in contractile responses of single smooth muscle cells from guinea pig ileum. PMID- 1507573 TI - All-or-none response of isolated smooth muscle cells from guinea-pig taenia caecum to acetylcholine. PMID- 1507574 TI - Effect of L-NG-nitro-arginine (L-NOARG) on the relaxation induced by gamma aminobutyric acid (GABA) and vasoactive intestinal peptide (VIP) in rat isolated duodenum. PMID- 1507575 TI - Modified low density lipoprotein stimulates nitric oxide synthesis in vascular smooth muscle cells. PMID- 1507576 TI - Mechanism of the reduction of endothelium-dependent vasodilation in spontaneously hypertensive rats. PMID- 1507577 TI - Endothelium dependent relaxation of human corpus cavernosum by bradykinin. PMID- 1507578 TI - Endothelium-dependent relaxation to alpha-methyl-5-hydroxytryptamine in isolated horse coronary arteries. PMID- 1507579 TI - Autocrine and paracrine actions of EDRF on intracellular Ca2+ of endothelial cells and vascular smooth muscle cells as identified by two-D image analysis. PMID- 1507580 TI - Endothelin-1- and endothelin-3-induced vasorelaxation via endothelium-derived nitric oxide. PMID- 1507581 TI - Inhibitory mechanisms of action of K+ channel openers on contraction induced by an agonist in canine coronary arterial smooth muscle. PMID- 1507582 TI - An analysis of the nitrate-like and potassium channel opening actions of KRN2391 in canine coronary arterial smooth muscle. PMID- 1507583 TI - Modulation of guinea-pig tracheal smooth muscle responsiveness by the potassium channel openers NIP-121 and cromakalim. PMID- 1507584 TI - Characterization of the vasodilatation by the K+ channel openers: cromakalim and pinacidil. PMID- 1507585 TI - Effect of BRL 38227 on K-currents in rat portal vein. PMID- 1507586 TI - Smooth muscle K-channel blocking properties of ciclazindol. PMID- 1507587 TI - Endothelin blocks ATP-sensitive K+ channels and depolarizes smooth muscle cells of porcine coronary artery. PMID- 1507588 TI - Effects of vasopressin on ATP-sensitive and Ca(2+)-activated K+ channels of coronary arterial smooth muscle cells. PMID- 1507589 TI - Metabolic alterations induced by obstructive hypertrophy of the rabbit urinary bladder. PMID- 1507590 TI - Hyperpolarization as a mechanism for endothelium-dependent relaxations in the porcine coronary artery. PMID- 1507591 TI - Properties of ATP-sensitive K+ channel in the smooth muscle cells of the rabbit portal vein. PMID- 1507593 TI - A novel regulatory effect of smooth muscle myosin light chain kinase on ATP dependent actin-myosin interaction. PMID- 1507592 TI - Membrane hyperpolarization inhibits agonist-induced synthesis of inositol 1,4,5 trisphosphate in rabbit mesenteric artery. PMID- 1507594 TI - Stimulatory and inhibitory effect of caldesmon on ATP-dependent interaction between actin and myosin in smooth muscle. PMID- 1507596 TI - Differentiation and structural organization of chicken gizzard smooth muscle. PMID- 1507595 TI - Cellular and molecular physiology of calcium signalling in smooth muscle cells. PMID- 1507597 TI - Effects of calcium and ethylene glycol on force transients on photogeneration of low concentrations of ATP in skeletal muscle fibers. PMID- 1507598 TI - Modification by magnesium of the excitatory effect of oxytocin on electrical and mechanical activities of pregnant human myometrium. PMID- 1507599 TI - Responses of A10 cells to Arg8-vasopressin and endothelin-1: the role of divalent cations. PMID- 1507600 TI - Arg-vasopressin increases nuclear [Ca2+] in single cultured vascular smooth muscle cells of rat aorta. PMID- 1507601 TI - Scopolamine-sensitive endothelial muscarinic receptors. PMID- 1507602 TI - Muscarinic receptors in the aortae of normo- and hypertensive rats. PMID- 1507603 TI - Selective binding of [3H]NMeQNB to a subpopulation of muscarinic receptors in single smooth muscle cells induces a temperature dependent decrease of receptor [3H]NMeQNB complex. PMID- 1507604 TI - Muscarinic receptor subtype in the airways. PMID- 1507605 TI - Biphasic effects of interleukin-2 on proliferation of cultured vascular smooth muscle cells. PMID- 1507606 TI - Diabetic state modifies insulin receptor activity dependent on glucocorticoid in cultured vascular smooth muscle cells of GK rat. PMID- 1507607 TI - Intracellular calcium measurement in isolated rat arterioles during phasic and tonic contractions. PMID- 1507608 TI - Pacemaker activity of pelvicalyceal site recorded by intracellular glass microelectrode. PMID- 1507610 TI - A simple mathematical model of spontaneous electrical activity in a single smooth muscle cell. PMID- 1507609 TI - Changes in the electrical properties of guinea pig smooth muscle membrane by experimental bladder outflow obstruction. PMID- 1507611 TI - Regional differences in adrenergic innervation in the myometrium of the swine uterus. PMID- 1507612 TI - Haloperidol-sensitive relaxation of the rat mesenteric artery to electrical field stimulation. PMID- 1507613 TI - Ranitidine action on responses of the rat anococcygeus muscle to field stimulation. PMID- 1507614 TI - Denervation supersensitivity after neuronal ablation in the rat colon. PMID- 1507616 TI - Contractile responses of the rat aortic strip to stonustoxin. PMID- 1507615 TI - Effects of methanol extract of ginkgo biloba (EGb), its ethylacetate fraction (EAF) and butanol fraction (BF) on the isolated aorta. PMID- 1507617 TI - Relatively immediate relaxant effects of cholera toxin on the isolated rabbit blood vessels. PMID- 1507618 TI - Ketamine-induced relaxation of rabbit portal vein. PMID- 1507619 TI - Relaxation mechanisms of antispasmodics papaverine and thiphenamil on the human corpus cavernosum. PMID- 1507620 TI - Possible involvement of NO pathway in PAF-induced vasorelaxation. PMID- 1507621 TI - Complex endothelium-dependent hyperpolarization in coronary arterial smooth muscle. PMID- 1507622 TI - Inhibitory effects of endothelium on contractile responses to acetylcholine in the pig coronary artery. PMID- 1507623 TI - Endothelium-dependent and -independent contractions to glycine in isolated vascular smooth muscles. PMID- 1507624 TI - An effect of LP-805 as an inducer of endothelium-derived nitric oxide on systemic vasodilation in vivo. PMID- 1507625 TI - The oscillation of Ca-activated K current induced by caffeine in rabbit pulmonary arterial cells. PMID- 1507626 TI - Maxi K+ channel activity stimulated by G kinase in the canine coronary arterial smooth muscle. PMID- 1507627 TI - Characterization of internal and external binding sites for tetraalkylammonium ion block of gastrointestinal Ca(2+)-activated K+ channels. PMID- 1507628 TI - Ca(2+)-dependent K+ current of guinea pig vas deferens. PMID- 1507629 TI - Characteristics of membrane currents in single rat myometrial cells. PMID- 1507630 TI - Effects of norepinephrine (NE) on membrane currents recorded from single ureter smooth muscle cells of the guinea-pig. PMID- 1507631 TI - Effects of ryanodine on myogenic tone and intracellular [Ca2+] in isolated rat skeletal muscle arterioles. PMID- 1507632 TI - Myosin in smooth muscle: from thick filaments to the cross-bridge cycle. PMID- 1507633 TI - Phosphatidyl inositol-turnover provides negative-feedback for excitation contraction coupling in gastric smooth muscle. PMID- 1507634 TI - Compartments of the Ca store in single smooth muscle cells and agonist-induced Ca release. PMID- 1507635 TI - Platelet-derived growth factor induces Ca2+ transients and proliferation of vascular smooth muscle cells: a role of tyrosine kinase. PMID- 1507636 TI - Platelet-derived growth factor induces c-fos and c-myc mRNA in cultured rat aortic smooth muscle cells irrespective of intracellular Ca2+ levels. PMID- 1507637 TI - Involvement of protein kinase C in Ca(2+)-independent contraction of rat uterine smooth muscle. PMID- 1507638 TI - Is staurosporine (ST) a specific inhibitor of protein kinase C (PKC) in intact porcine coronary arteries? PMID- 1507639 TI - Calcium ion-independent contraction of bladder smooth muscle. PMID- 1507640 TI - Staurosporine prevents the impairment of endothelium-dependent relaxation by oxidized-LDL in pig coronary arteries. PMID- 1507641 TI - Electrical and mechanical activity of the rumen complex of sheep. PMID- 1507642 TI - Mechanism of GTP gamma S-dependent regulation of smooth muscle contraction. PMID- 1507643 TI - Calcium-dependent and calcium-independent pathways of signal transduction in smooth muscle. PMID- 1507645 TI - Do the cytoplasmic and muscle-specific isoforms of actin and myosin heavy and light chains serve different functions in smooth muscle? PMID- 1507644 TI - Pharmacomechanical coupling: the role of G-proteins in Ca(2+)-release and modulation of Ca(2+)-sensitivity. PMID- 1507646 TI - Smooth muscle--into the 1990s. PMID- 1507647 TI - Energetics and regulation of smooth muscle contraction. PMID- 1507648 TI - Contribution of Ca(2+)-induced Ca2+ release to depolarization-induced Ca2+ transients of myocytes from guinea-pig urinary bladder myocytes. PMID- 1507650 TI - Effects of psychoactive drugs on short-term memory in rats and rhesus monkeys. AB - To examine the effects of drugs on short-term memory in animals, the delayed discrimination experiment in rats and the delayed matching to sample experiment in rhesus monkeys were conducted. Nicotine at 0.125 mg/kg, s.c. in rats and at 0.5 mg/kg, s.c. in monkeys increased the percentages of correct choices. Scopolamine at 0.06-0.12 mg/kg, s.c. in rats and at 0.015 mg/kg, s.c. in monkeys decreased the percentages of correct choices. However, supposedly memory specific, delay-time-dependent disruptive effects by scopolamine were found only in monkeys. Diazepam at 0.5-2 mg/kg, s.c. did not change the correct choices in rats. However, diazepam at 1-4 mg/kg, i.g. decreased the correct choices in monkeys regardless of the delay time. Chlorpromazine at 0.25-1.5 mg/kg, s.c. showed inconsistent effects in rats. In monkeys, chlorpromazine at 0.25-0.5 mg/kg, s.c. had no effect. These results suggested that using both rats and monkeys would be useful for evaluating the effects of drugs on memory. PMID- 1507649 TI - The role of intestinal bacteria in the transformation of sodium picosulfate. AB - Sodium picosulfate, a laxative, was biotransformed to 4,4'-dihydroxydiphenyl-(2 pyridyl)-methane by intestinal flora that produced a novel sulfotransferase (not sulfatase). The biotransformation was activated by adding phenolic compounds such as phenol, acetaminophen and flavonoids. The enzyme activity related to this biotransformation was the highest in the contents of the caecum region of the intestine. The enzyme activity was 3.0 mumole/hr/g wet feces in humans and 0.75 in rats (pH 8.0). The optimal pH was 9.0. PMID- 1507651 TI - Chronopharmacology of probucol in mice. AB - Mice were maintained under conditions of light from 7 a.m. to 7 p.m. and dark from 7 p.m. to 7 a.m. Probucol was given orally to these animals once daily at 10 a.m. or 10 p.m. for 7 days. Blood samples for serum cholesterol were obtained at 24 hours after the final dosage. Blood samples for plasma probucol were obtained just before and at 3, 6, 12, 24, 48, 72, 96 and 120 hours after the final dosage. The cholesterol lowering effect of the agent at 10 p.m. was greater than that at 10 a.m. Plasma probucol concentrations of the two trials did not differ at any observation point. These data suggest that the effect of probucol varies with its time of administration. This might not be caused by a time-dependent change in plasma probucol concentration. PMID- 1507652 TI - Cholecystokinin protects cholinergic neurons against basal forebrain lesion. AB - Alzheimer's Disease (AD) patients have a severe degeneration of cholinergic neurons in their cerebral cortices. Basal forebrain (BF)-lesioned rat is used as a model animal of a cholinergic deficit in the cerebral cortex. Cholinergic markers were decreased in the cerebral cortex of BF-lesioned rats. Intracerebroventricular continuous infusion of cholecystokinin octapeptide (CCK8) following BF lesion obviously preserved these cholinergic markers. These results suggest that CCK8 prevents the degeneration of cholinergic neurons in the cerebral cortex following BF lesion. PMID- 1507653 TI - Effects of anti-asthma drugs and potassium channel openers on neurally-mediated contraction of isolated guinea pig trachea. AB - The effects of anti-asthma drugs, isoproterenol, aminophylline and hydrocortisone, and potassium channel openers on the contraction induced by electrical stimulation or exogenously applied acetylcholine were investigated in isolated guinea pig trachea. Isoproterenol and aminophylline non-selectively inhibited both the contraction evoked by vagus nerve- and that by transmural field-stimulation, but had no effect on the response induced by exogenously applied acetylcholine. Hydrocortisone and potassium channel openers, NIP-121 and cromakalim, preferentially inhibited vagus nerve-mediated response. These results suggest that anti-asthma drugs may have an ability to inhibit neurally-mediated contraction in the guinea pig trachea. PMID- 1507654 TI - Protective effects of benidipine on arachidonic acid-induced acute cerebral ischemia in rats. AB - Acute cerebral ischemia was produced in rats by injection of arachidonic acid (AA) into the internal carotid artery. Evans blue (EB) was intravenously injected and its extravasation into the brain was determined as an indicator of disturbances in the blood-brain barrier and endothelial cells. Control animals showed severe cerebral edema and marked blue staining of the brain. Benidipine (30 micrograms/kg, i.p.) suppressed the increase in cerebral water content and the extravasation of EB. Similarly nicardipine (100 micrograms/kg, i.p.) suppressed the elevation of water content and the extravasation of EB. Furthermore, both benidipine (30 micrograms/kg, i.p.) and nicardipine (100 micrograms/kg, i.p.) improved the neuronal injuries following AA-injection. An antiplatelet agent, ticlopidine (100 mg/kg, i.p.), and a thromboxane A2 synthetase inhibitor, OKY-1581 (3 mg/kg, i.p.), also suppressed the elevation of cerebral water content. A lipoxygenase inhibitor, AA-561 (200 mg/kg, p.o.), and a cyclooxygenase inhibitor, indomethacin (10 mg/kg, i.p.), did not prevent the increase in cerebral water content. Neither benidipine (3-30 micrograms/kg, i.v.) nor nicardipine (100 micrograms/kg, i.v.) inhibited the AgNO3-induced thrombus formation of the abdominal aorta, whereas ticlopidine (100 mg/kg, p.o.) and OKY 1581 (3 mg/kg, i.v.) prevented the thrombus formation. From the present results, it is suggested that benidipine, as well as nicardipine, may protect against AA induced acute cerebral infarction via a mechanism independent of antithrombotic action. PMID- 1507655 TI - The role of endothelium in the phenylephrine-induced oscillatory responses of rabbit mesenteric arteries. AB - Phenylephrine-induced oscillatory contractions in rabbit mesenteric arteries were investigated in vitro. Adrenergic, cholinergic, or histamine antagonists as well as cyclooxygenase and lipoxygenase inhibitors had no effect on this phenylephrine induced oscillation. The removal of extracellular calcium ions or treatment with a calcium antagonist reduced the amplitude and frequency of the oscillation. Removal of the endothelium or treatment with inhibitors of the synthesis or the target enzyme of endothelium-derived relaxing factor (EDRF) also reduced the amplitude and frequency of the oscillation. In a perfusion bioassay, the perfusate from an endothelium-intact arterial segment induced oscillation of an endothelium-denuded arterial ring recipient. These results suggest that phenylephrine-induced oscillation is mediated by an endothelium-derived factor such as EDRF and depends on the influx of extracellular calcium ions. PMID- 1507656 TI - Beneficial effect of intravenous taurine infusion on electroretinographic disorder in taurine deficient rats. AB - We investigated the effect of intravenous taurine infusion on the electroretinogram (ERG) of taurine-deficient rats produced by treatment with guanidinoethyl sulfonate (GES), a taurine transport inhibitor. Mother rats were fed a taurine-free diet and given drinking water containing 1% GES from 2 weeks of gestation to weaning. The same feeding conditions were applied to male offspring after weaning. Both ERG measurement and continuous infusion of taurine at a dose of 10, 30 or 100 mg/animal/day were performed for 3 weeks from 7 to 10 weeks of age. GES-treatment reduced a- and b-wave amplitudes to 50% of the control levels and also increased b-wave latencies. Intravenous infusion of taurine improved these ERG abnormalities in a dose-dependent manner. Taurine concentrations in plasma, eyes and brain were also decreased by treatment with GES, and dose-dependent recovery was observed after infusion with taurine, although the concentrations of other amino acids were not affected by GES treatment and infusion of taurine. Observations of morphological changes revealed that the retinal damage in GES-treated animals was decreased by taurine infusion. These results indicate that the changes in ERG and retinal structure observed in taurine deficiency are improved by intravenous infusion of taurine. PMID- 1507657 TI - Platelet-derived growth factor (PDGF) accelerates induction of competence, and heparin does not inhibit PDGF-induced competence in primary cultured smooth muscle cells of rat aorta. AB - The time-dependent effect of platelet-derived growth factor (PDGF) on cell proliferation was investigated to clarify whether PDGF accelerates the rate of proliferation or its start in primary cultured smooth muscle cells (SMC) of rat aorta. In synchronized SMC at the G0 phase, 1, 10 and 100 ng/ml PDGF started DNA synthesis at 24, 15-18 and 12 hr, respectively, after stimulation by 3% fetal bovine serum (FBS) or hypophysectomized rat plasma (deficient in insulin-like growth factor-I (IGF-I)). Heparin (1, 10 or 100 micrograms/ml) decreased only the rate of DNA synthesis stimulated by PDGF in synchronized SMC. DNA synthesis in non-synchronized cells stimulated by PDGF with FBS was determined up to 10 days in culture. The stimulation with 1% FBS plus 30 ng/ml PDGF potentiated the DNA synthesis which was saturated with stimulation by 10% FBS alone, suggesting that prolonged treatment of PDGF transforms SMC. These results demonstrated that PDGF concentration-dependently accelerated the induction of competence independently of IGF-I, and heparin did not inhibit PDGF-induced competence but inhibited progression in primary cultured SMC of rat aorta. PMID- 1507658 TI - Inhibitory effect of OP-41483.alpha-CD, a prostacyclin analog, on peripheral vascular lesion models in rats. AB - The effect of a chemically stable prostacyclin analog, OP-41483 alpha cyclodextrin clathrate (OP-41483.alpha-CD), on vascular lesions, platelet aggregation and blood pressure were examined and compared with those of prostaglandin E1 alpha-cyclodextrin clathrate (PGE1.CD) in in vivo rat models. 1) In the laurate (1 mg/leg, i.a.)-induced arterial thrombotic model, OP-41483.alpha CD (1 microgram/kg/min, i.v.) prevented the progression of femoral arterial vascular lesions and enhanced the development of collaterals in the femoral artery. PGE1.CD did not inhibit the progression of vascular damages. 2) In the model of vasoconstriction induced by epinephrine (0.05 mg/tail, s.c.) and ergotamine (2 mg/kg, s.c.), OP-41483.alpha-CD and PGE1.CD, at 1 microgram/kg/min, inhibited the progress of of tail gangrene and lessened the decrease in tail cutaneous blood flow. 3) OP-41483.alpha-CD (1 microgram/kg/min) suppressed the ADP (0.1 mg/kg/min, i.v.)-induced decrease in the number of circulating platelets without affecting the change in blood pressure. In contrast, PGE1.CD (3 micrograms/kg/min) inhibited ADP-induced thrombocytopenia with a decrease in blood pressure. These results indicate that OP-41483.alpha-CD has antiplatelet and cutaneous blood flow improving activities that are greater than its hypotensive effect and may be of therapeutic potential in peripheral vascular diseases. PMID- 1507659 TI - Effects of pravastatin sodium alone and in combination with cholestyramine on hepatic, intestinal and adrenal low density lipoprotein receptors in homozygous Watanabe heritable hyperlipidemic rabbits. AB - Pravastatin sodium (pravastatin), a tissue-selective inhibitor of 3-hydroxy-3 methylglutaryl coenzyme A reductase, was administered alone (50 mg/kg) or in combination with cholestyramine, a bile acid sequestrant resin, at the level of 2% in the diet to homozygous Watanabe heritable hyperlipidemic (WHHL) rabbits for 4 weeks. The low density lipoprotein (LDL)-cholesterol levels were reduced by 29% and 56% with pravastatin alone and the combination treatment, respectively. Hepatic LDL receptor activity was increased by 11.2- and 13.9-fold with pravastatin alone and the combination treatment, respectively. The LDL receptor activity in the untreated homozygous WHHL rabbits was only 2.5% of that in the normal rabbits. mRNA for the LDL receptor in the liver was also increased by 2.1- and 3.4-fold with pravastatin alone and the combination treatment, respectively. On the other hand, mRNA for the LDL receptor in the adrenal gland was not affected by pravastatin and the combination treatment, whereas the mRNA in the intestine was increased in both groups. These results suggest the following: 1) the induction of hepatic LDL receptor activity by the treatment of pravastatin alone or in combination with cholestyramine is the main cause of the reduction of serum cholesterol levels by these treatments even in LDL receptor-deficient animals. 2) The induction of the mRNA for the LDL receptor in the liver and intestine, but not that in the adrenal gland, might be a reflection of the tissue selective inhibition of cholesterol synthesis by pravastatin. PMID- 1507660 TI - Basic fibroblast growth factor ameliorates learning deficits in basal forebrain lesioned mice. AB - The effect of basic fibroblast growth factor (bFGF) treatment on memory and learning performance ability was investigated in basal forebrain (BF)-lesioned mice. Eight-week-old male ddY mice underwent bilateral BF lesions by delivery of radiofrequency current. Basic FGF (5 or 50 ng/side) was microinjected into the same location immediately after lesioning. From fifteen days after the treatment, a step-through type passive avoidance test was performed daily for 10 days. Lesioned animals showed severe impairment in the acquisition process in this task, but not in the retention process. Basic FGF improved the step-through performances; step-through latency was elongated in a dose-dependent manner on the first test trial day and the mean time required to reach the acquisition criterion was shorter than in the vehicle-treated control group. However, bFGF did not alter the cortical choline acetyltransferase (ChAT) activity decrement induced by BF lesion. These results suggest that bFGF ameliorates the memory deficit without affecting the cortical ChAT activity. PMID- 1507661 TI - Effect of pentazocine on the cytotoxicity of cortisone-resistant lymphocytes from mouse thymus. AB - Pentazocine and its related compounds were examined for their effect on the cytotoxicity of cortisone-resistant lymphocytes (CR lymphocytes) against Ehrlich carcinoma cells. The following compounds were used: pentazocine, naloxone, levallorphan, eptazocine and morphine. CR lymphocytes were obtained from the thymus or spleens of mice injected i.p. with hydrocortisone acetate (125 mg/kg) 2 days before harvesting the lymphocytes. The mixture of tumor cells and CR lymphocytes was inoculated s.c. into mice after incubation in the presence or absence of 10 microM drugs. Five weeks after inoculation, the percentage of mice developing a solid tumor among the recipients given the pentazocine-treated cell mixture of tumor cells and thymic CR lymphocytes was significantly smaller than the percentage in recipients given the cell mixture treated with or without other drugs (percent tumor takes: 21% and about 80%, respectively). Splenic CR lymphocytes did not show any cytotoxic effect, irrespective of the drug treatment. The pretreatment of CR lymphocytes or Ehrlich cells with 10 microM pentazocine did not affect the cytotoxicity of thymic and splenic CR lymphocytes. The proportion of the lymphocyte-conjugated tumor cells was significantly increased when the mixture of CR lymphocytes and tumor cells was incubated in the presence of pentazocine. The present results indicate that the cytotoxicity of thymic CR lymphocytes is enhanced by pentazocine possibly through the increase in the proportion of the lymphocyte-conjugated tumor cells but enhanced not by the other drugs. PMID- 1507662 TI - Studies on antinephritic effects of plant components (3): Effect of pachyman, a main component of Poria cocos Wolf on original-type anti-GBM nephritis in rats and its mechanisms. AB - The antinephritic effect of pachyman on original-type anti-GBM nephritis in rats was investigated. Pachyman was given to original-type anti-GBM nephritic rats for 10 days from the day of anti-GBM serum injection. Pachyman prevented urinary protein excretion and the elevation of serum cholesterol content. Histopathological observations of the glomeruli indicated that although the number of nuclei and adhesion to capillary walls of Bowman's capsule in nephritic control rats were significantly increased, pachyman reduced the degree of histopathological changes such as hypercellularity and adhesion as compared to the control group. Although the serum complement CH50 ratio in control group was significantly lower than that in the normal group, the decrease in serum complement CH50 was inhibited by pachyman, and rat C3 deposition in the glomeruli in the pachyman-treated group was significantly reduced. These results suggest that pachyman was effective against original-type anti-GBM nephritis in rats and that the antinephritic mechanisms of pachyman may be partly due to the inhibitory action of this agent on C3 deposition in the glomeruli. PMID- 1507663 TI - Ca2+ ionophore and phorbol ester stimulate diacylglycerol formation and phosphatidylcholine hydrolysis in rat parotid acinar cells. AB - We investigated the effects of A23187 and phorbol 12,13-dibutyrate (PDBu) on sn 1,2-diacylglycerol (DAG) accumulation and phosphatidylcholine (PC) hydrolysis in rat parotid acinar cells. Both A23187 and PDBu, in concentration ranges of 0.001 0.1 microM, stimulated DAG accumulation and PC hydrolysis in a time- and concentration-dependent manner. Treatment with A23187 and PDBu stimulated the release of [3H]choline and [3H]phosphocholine into the medium, indicating [3H]PC hydrolysis is due to the activation of phospholipases C and D; however, [3H]phosphatidylethanolamine hydrolysis was not indicated. These releases were unaffected by the addition of glucose 6-phosphate, a phosphatase inhibitor. Staurosporine, a protein kinase C inhibitor, significantly inhibited the DAG accumulation and the PC hydrolysis stimulated by these agents. Combinations of A23187 and PDBu potentiated the stimulatory effect which each of these agents alone had on DAG accumulation and PC hydrolysis. This mode of action was additive but not synergistic. These results suggest that DAG accumulation induced by A23187 and PDBu is related to the PC hydrolysis mediated via the activation of phospholipases C and D, and that it is not related to phosphatidylethanolamine hydrolysis. PMID- 1507664 TI - [Itch and the heat tolerance scale: effects of thermographic biofeedback]. AB - Effects of heat tolerance (HT) relating with individual emotionality, and of thermal biofeedback on itching were examined. Fourteen high HT subjects and 12 low HT subjects were selected by the Cold and Heat Tolerance Scales (Dienstbier, LaGuardia, & Wilcox, 1987). The experiment was divided into three phases: rating of itch, eight thermal biofeedback (increase or decrease) training sessions, and rating of itch with biofeedback. Itching was produced by a glue made from Japanese yam powder. Yam glue was applied on the subjects' dorsal forearm. The biofeedback information was given by the thermographics on the CRT, where its color was changed according to the changes in temperature of the dorsal forearm skin. Results showed that (a) subjects who were instructed to decrease their skin temperature reported comparatively lower intensities of itching, although their actual temperature controls were unsuccessful, and (b) the biofeedback performance reduced the intensity of itching for the low HT subjects, but raised it for the high HT subjects who were instructed to increase their skin temperature. The results suggested that the biofeedback performance could have different central effects on itching among the HT groups. PMID- 1507665 TI - [The effect of motivation on preschool children's sharing judgment and behavior]. AB - The purpose of this study was to examine the effect of motivation on preschool children's sharing judgment and behavior. In Experiment 1, 45 4-year-olds and 41 5-year-olds were asked whether they wanted to share seals in a fictional situation, and were observed whether they shared their seals in an actual situation. The main results indicated that the number of children who shared seals in the latter situation was smaller than those who judged to share seals in the former one. Especially there was a great difference regarding this point in 4 year-olds children. "Empathic orientation" motivated preschool children's sharing behavior, while "self-focused orientation" did not. In Experiment 2, 52 4-year olds and 60 5-year-olds were divided into two empathic levels (middle, high) and two motivational cost levels (low, high) to examine the effects of "empathic orientation" and "self-focused orientation." The main results indicated that high motivational cost restrained children from sharing in an actual situation. PMID- 1507667 TI - [Formation of grand coalition when consciousness of intragroup competition is activated]. AB - The purpose was to explore conditions encouraging to form grand coalition, which leads a group to high solidarity with strong consciousness of intragroup competition. Subjects, 64 male undergraduates, were divided into 16 groups of four persons each. Experiment was carried out with 2 x 2 design of (consciousness of intergroup competition: strong vs. weak) (consciousness of intragroup competition: strong vs. weak). Results showed that strong competitive spirits against other groups produced facilitative effects on formation of grand coalition even when the consciousness of intragroup competition was strong, and the facilitative effects were strong even when consciousness of intragroup competition was weak. In addition, the necessary conditions for group members to form grand coalition under strong intragroup competition were discussed. PMID- 1507666 TI - [Construction of a multiple mood scale]. AB - A self-report instrument to measure multiple mood states was constructed. Six hundred and forty-eight Japanese affect adjectives were collected and divided into two lists. Japanese undergraduates totaling 1,254 rated each adjective in the list on a 4-point intensity scale to assess their momentary mood states. Factor analyses revealed 131 items with high loading on extracted major factors. The new list of these 131 items was rated three times by undergraduates totaling 1,768 and was factor analysed. Throughout the factor analyses, eight factors emerged with consistent reliability. Finally, 80 items highly loaded on these factors were selected to construct eight 10-item mood scales. These scales were called Depression (Anxiety), Hostility, Boredom, Liveliness, Well Being, Friendliness, Concentration and Startle. The scales were shown to be internally consistent. A comparison of these scales with the English mood scales was presented. PMID- 1507668 TI - [Preschool children's prosocial judgments and their reasoning in the empathic situations]. AB - The purpose of this study was to examine preschool children's prosocial judgments and their reasoning for prosocial episodes. One hundred children were individually asked to do prosocial judgments and their reasoning for three prosocial episodes: helping, sharing, and comforting. In the episode there was a crying or a normal facial expression of a person in distress under the condition of high and low empathic situations. The results indicated that the crying face and high empathic situation increased the rate of prosocial judgment more than the normal face and low empathic situation, respectively, and older children (5 year-olds) did prosocial judgment than younger ones (4-year-olds). Furthermore, the crying face induced the empathic reasoning, especially in the high empathic situation. These results supported that preschool children were able to use the empathic reasoning reflected in the negative facial expression and the cause of distress of the victim. PMID- 1507669 TI - [A mediating role of physiological arousal in social facilitation]. AB - An experiment was conducted to examine the mediating role of physiological arousal in social facilitation. It was hypothesized that the elevation of arousal level by the presence of other persons or evaluative apprehension would facilitate task performance. Twenty-four male and 24 female college students performed simple task alone, with a cooperative person, or with a competitive person. One half of the subjects was given an instruction which would produce evaluative apprehension. Subjects' skin potential responses were measured as the indices of physiological arousal. Although the hypothesis was supported by the analysis of psycho-physiological index, but it was not at all by the self reported index of arousal. PMID- 1507670 TI - [Conditioned aversion to an intraperitoneally injected odor CS in rats]. AB - Two experiments were conducted to specify an CS property of intraperitoneally injected odor substance in conditioned odor aversion formation. In experiment 1, three groups of water-restricted rats received one trial of conditioning with intraperitoneal injections of orange-extract (CS) and LiCl(UCS). The CS-UCS intervals of experimental groups were 30 minutes (Group IE-30) and 120 minutes (Group IE-120). In the test trial, Group IE-30 rats showed aversion to the test solution (0.5% orange extract), whereas no significant difference was observed between the control group and Group IE-120. In experiment 2, three groups of rats received one or two or three conditioning trials (Groups E1, E2 and E3, respectively). The CS-UCS interval of all groups was 30 minutes. In the test trial, rats in Groups E2 and E3 consumed less amount of test solution (0.5% orange extract) than the control rats, whereas no significant difference was observed between Group E1 and the control group. These results suggest that the intraperitoneally injected odor substance have CS property on conditioned odor aversion. PMID- 1507671 TI - [Effects of inclination of trunk and head on emotional awareness]. AB - Posture is a nonverbal behavior and a universal means of animal and human communication. It is observed not only in interpersonal communication but in clinical situation. Our recent research shows that posture affects the mood and emotional awareness of the subjects. This study compared the subjects' awareness between two groups, the operational group (actual posture) and the image group, which only imagined a postural change. Six kinds of posture were adopted. These postures included two dimensions; inclination of trunk (straight or bent), and head (up, front or down). In these conditions the subjects estimated their mood and emotional awareness with 17 pairs of adjectives on a 3 point scale. The results of ANOVA showed statistically significant differences in conditions of both inclination of trunk and head. Especially, when the subject bent his back while hanging his head, this made most feeble, lifeless, and shadowy mood than any other postures. The authors confirmed that posture exerted a strong influence on one's emotional awareness. PMID- 1507672 TI - [The current status of psychology in Korea]. AB - This paper read as the special lecture at the Annual Convention of The Japanese Psychological Association, held at Tokyo Metropolitan University in 1990, and reported on the recent trends of psychology in the Republic of Korea. This report dealt essentially with four topics; 1) the history of Korean psychology which was divided into four periods of creation, reconstruction, development, and current status, after the liberation at the end of the World War II in 1945, 2) the distribution and academic status of 26 universities, with formal department of psychology, 3) general situation of job opportunities for the graduates in psychology of these universities, 4) the composition of Korean Psychological Association (KPA), consisting of nine divisions (social, industrial and organizational, clinical, consultations and psychotherapy, experimental and cognitive, developmental, biological and physiological psychology) with the total of about 400 members. Last, some directions of Korean psychology to the future was suggested. PMID- 1507673 TI - [Nd-YAG laser treatment for central airway lesions]. AB - YAG laser treatment was conducted in 55 patients with central airway lesions over the last 8 years. The malignant lesions comprised 1 primary tracheal cancer, 1 chondroma of the trachea, 34 primary lung cancer, and 10 metastatic lung tumor. The benign lesions comprised one each of hamartoma, lipoma, bronchial lithiasis, post-tracheotomy granuloma, and bronchial web, and 3 other cases. Nd-YAG laser treatment was performed in 55 patients with airway lesions, with a success rate of 73%. The success rates in the above patients were 70% for primary lung cancer, 60% for metastatic lung tumor, 100% for primary tracheal cancer and chondroma of trachea, and 89% for benign lesions. In 34 patients with primary lung cancer, palliative widening of the airway was planned with the exception of 2 patients with endoscopically early lung cancer for whom curative vaporization was intended, 6 months-survival rate was 59.3% in patients in whom various combined treatments were performed after the laser treatment. For all patients with hamartoma or lipoma in those with benign lesions, curative vaporization was performed. The severe complication of lethal massive hemoptysis occurred in 3 patients. We consider that Nd-YAG laser treatment is a powerful therapeutic means of performing lifesaving or emergency, curative, and supplemental treatment. PMID- 1507674 TI - [Tracheobronchial reconstruction in infants and children]. AB - Fifty-eight infants and children with various tracheobronchial obstructions were surgically treated at Kobe Children's Hospital between 1980 and 1991. The lesions included subglottic stenosis (24), congenital tracheal stenosis (9), tracheomalacia (15), bronchomalacia (6), and others (4). The operative procedures included laryngotracheoplasty using costal cartilage or anterior cricoid split for subglottic stenosis, tracheoplasty with costal cartilage graft for extensive tracheal stenosis, aortopexy for tracheomalacia, and external stenting or bronchial resection with tracheo-bronchial anastomosis for bronchomalacia. In 46 of 58 patients, the endotracheal tube was successfully removed and the patient remained free of respiratory symptoms. These operative results encourage us to continue all surgical procedures except for external stenting for bronchomalacia, which did not correct the collapse of the bronchus. PMID- 1507675 TI - [Surgical treatment of tracheobronchial lesions in children]. AB - A total of 16 cases of tracheal and bronchial lesions such as bronchial tumor (4 cases), aspirated foreign body (5 cases), and tracheo-bronchial stenosis (7 cases) were surgically treated at the National Children's Hospital from 1965 to 1990. A mucoepidermoid tumor was excised via bronchotomy. Pulmonary lobectomy was indicated for another 2 mucoepidermoid tumors which arose from the middle and lower lobe bronchus. Pneumonectomy was indicated for a leiomyoma located at the stem of the left bronchus and showed extensive invasion into the bronchial wall. It is important to accurately diagnose the location and extent of the tumor by performing intraoperative bronchoscopy, bronchotomy, frozen section examination in order to avoid unnecessary pulmonary resection. Three aspirated foreign bodies (2 marking needles and a peanut) were removed via bronchotomy. Right lower lobectomy was performed in a patient who received an accidental injection of barium sulfate into the right lower bronchus. The barium remained for more than one year and caused recurrent pneumonia. A radiolucent toy plate aspirated into the left main bronchus of a 3-year-old girl was overlooked for more than 3 years. Suppurative changes of the left lung necessitated pneumonectomy. Tracheal resection with end-to-end anastomosis was carried out successfully in a 5-year old patient suffering from segmental fibrogranulous stenosis of the mid-trachea. Extensive congenital stenosis in 6 patients was repaired by costal cartilage autograft, with a 67% mortality rate. Treatment of the associated cardiac anomalies and the possible postoperative complications such as anastomotic leakage, restenosis, exuberant granulation, and tracheomalacia are the major problems associated with this type of tracheoplasty. PMID- 1507676 TI - [Diagnosis, incidence, clinicopathology and surgical treatment of acquired tracheobronchomalacia]. AB - We report our recent findings on the diagnosis, incidence, appearance of the trachea at autopsy, and surgical treatment of acquired trachobronchomalacia. In the diagnosis of this disease, continuous dynamic CT scanning (1 slice/0.6 second) from inspiration to deep expiration was better than X-ray cine recording. It is difficult to observe the most collapsed airway on coughing using bronchofiberscopic recording, because its duration time was estimated to be 1/10 second by X-ray cine recording, whereas the findings at one instant were easily recorded by video-bronchoscopy on coughing. The degree of severity of this disease was classified into three groups. 1st degree 0-50% narrowing of airway caliber, 2nd degree 50-75%; and 3rd degree 75-100%. Severity of 2nd or 3rd degree was present in 542 (12.7%) of 4283 patients suffering from chest disease who underwent bronchoscopy. Seventy-two percent of patients were aged 50 to 80 years. Third degree tracheomalacia was found in 131 patients with an incidence of 3.1%, which increased from 2.2% at 50 years to 6.2% at 80 years. The autopsy findings of the trachea consisted of fragmentation of the tracheal cartilage and extension of the membranous portion. The pathogenesis may be varied with different types of collapse of the airway, including the saber sheath type and the crescent type. Surgical treatment consists of prevention of the airway collapse by wrapping the airway with Marlex mesh and bonding Lyodura (lyophilized dura mata) with fibrin glue, which is more reliable than the span plasty proposed by Nissen. PMID- 1507677 TI - [Operative indications for tracheobronchomalacia]. AB - Tracheobronchomalacia in 3 children and 4 adults was reviewed, and operative indications were investigated. Tracheobronchomalacia in children differed from that in adults in that the lesion was localized and spontaneous healing was effected by cartilage growth and hardening. In adults, tracheobronchomalacia was characterized by a notch on the expiratory flow volume curve and higher V peak of inspiratory flow volume curve than that of expiratory curve. Operative indications for tracheobronchomalacia are BP higher than 28.2 cmH2O and delta CT higher than 15.4 cmH2O. Of 2 patients with tracheobronchomalacia in whom airway pressure was measured, one was a candidate for operation, and in the other, surgery was contraindicated because of low BP due to chronic obstructive pulmonary disease. PMID- 1507678 TI - [Role of psychological factors as a determinant of the hypercapnic ventilatory response and dyspnea sensation]. AB - We examined, in 38 healthy adult subjects (male 15, female 23), the relationship between psychological background as assessed by manifest anxiety scale test and Yatabe-Guillford test, and the hypercapnic ventilatory response (HCVR), which was tested twice with and without inspiratory resistive loading (17 cmH2O/L/sec). In addition, we attempted to evaluate the possible role of psychological factors in dyspnea sensation felt during HCVR, which was simultaneously assessed by visual analogue scaling (VAS). The slope value of HCVR was positively correlated with the social extraversion score in the male group (r = 0.55, p less than 0.05) only when the test was conducted without resistive loading. In the female group, it was positively correlated with emotional instability in both conditions (r = 0.46, p less than 0.05) without resistive loading and r = 0.47, p less than 0.05 with resistive loading). With respect to dyspnea sensation, manifest anxiety score alone had a positive correlation with VAS score evaluated in relation to ventilation only in the male group (r = 0.61, p less than 0.05). From these findings, we conclude that psychological factors may play a role as a determinant of HCVR, regardless of the presence of inspiratory resistive loading, as well as a determinant of the sensation of dyspnea during HCVR. PMID- 1507679 TI - [Leukocyte number, protein-inhibitor, and complement in smokers]. AB - In the present study, the number of leukocytes was increased in smokers, dependent on the amount of exposure to smoke (duration and cigarette number/day). The differential leukocyte count did not differ between smokers and non-smokers. Leucocyte-associated serum components such as alpha 1-antitrypsin, alpha 2 globulin, and complements did not differ in smokers. There was no relationship between neutrophils in peripheral blood and BAL fluid. These findings suggest that an increased number of leukocytes in smokers is not attributable to activation of complement, and that anti-proteinase serum levels including alpha 1 antitrypsin and alpha 2 globulin are unchanged in both smokers and ex-smokers. PMID- 1507680 TI - [A clinico-pathological study of 14 open lung biopsy cases of clinically suspected diffuse panbronchiolitis]. AB - To elucidate the relationship between clinical and histopathological findings in diffuse panbronchiolitis (DPB), we reviewed 14 open lung biopsy cases clinically suspected of having DPB. According to the histopathological criteria for "PB unit lesion" proposed by Kitaichi in 1988, 11 cases were diagnosed as having DPB; 3 cases were excluded by the criteria. The pathological diagnosis was not concordant with the evaluation according to the clinical diagnostic criteria for DPB previously proposed by Homma et al. in 1983. The present results indicate 1) the necessity to reexamine the pathological criteria for DPB, especially in open lung biopsy cases, and 2) the difficult differential diagnosis between DPB cases and non-DPB ones by current clinical diagnostic criteria. PMID- 1507681 TI - [Effect of enkephalinase inhibitor on endothelin-1 induced bronchoconstriction in guinea pigs]. AB - Endothelin-1 (ET-1) is one of the most potent bronchoconstrictors in the guinea pig. The mechanism of its metabolism is still unclear. Phosphoramidon is known to be an enkephalinase inhibitor. We studied the effect of phosphoramidon on bronchoconstriction induced by ET-1. In the first in vitro study, a tracheal preparation was mounted in oxygenated Krebs-Ringer solution. The response was monitored by isometric transducer. Dose-response curves to ET-1 with or without phosphoramidon were obtained. Phosphoramidon potentiated ET-1 induced bronchoconstriction significantly. Next, the specific airway conductance (sGaw) was measured in conscious guinea pigs exposed to an aerosol of phosphoramidon or saline, followed by ET-1 aerosol inhalation. The ET-1 dose was increased by successively doubling the concentration. sGaw, after inhalation of phosphoramidon, was significantly reduced when exposed to ET-1. Phosphoramidon also potentiated ET-1 induced bronchoconstriction in vivo. Next, lung parenchymal tissues were prepared and placed in oxygenated Krebs-Ringer solution with or without phosphoramidon. ET-1 was added and incubated, and samples were injected into a high performance liquid chromatography column. Phosphoramidon inhibited an analysis of ET-1. These data suggest that enkephalinase plays a role in the break down of ET-1 in the airway of the guinea pig. Under the condition of decreased enkephalinase, ET-1 would potentiate bronchoconstriction. PMID- 1507682 TI - [Evaluation of tissue eosinophils in eosinophilic pneumonia]. AB - Transbronchial biopsy specimens from ten patients with eosinophilic pneumonia were analysed to see whether the tissue contained activated eosinophils or secreted eosinophil cationic protein. The specimens showed many infiltrated tissue eosinophils in the intraalveolar spaces, and thickened alveolar septae and perivascular areas. Most of these eosinophils stained clearly with degranulation by immunohistochemical studies with monoclonal antibody EG2 (for the secreted form of eosinophil cationic protein), indicating that they were activated eosinophils. On the other hand, although pleural tissue obtained at bullectomy performed after pneumothorax showed eosinophilic infiltration, EG2-positive cells were few. Activated eosinophils may play an important role in the development of pulmonary lesions of eosinophilic pneumonia. PMID- 1507683 TI - [Clinical study on cough variant asthma]. AB - Chronic cough may be the sole presenting manifestation of bronchial asthma (reference 3; Corrao et al, 1979), and "cough variant asthma (CVA)" has been used to categorize such patients. In order to clarify the clinical picture of CVA, we evaluated the clinical history, laboratory data, sputum cytology and pulmonary function in 14 subjects (5 males and 9 females, aged 14 to 65 years) compatible with the following diagnostic criteria: (1) chronic cough persistent for more than 8 weeks, (2) no wheeze nor dyspnea, (3) no rales, (4) no past history of asthma, (5) bronchial hyperreactivity to methacholine proven by Takishima's method (reference 13), (6) effectiveness of bronchodilators against cough, (7) normal chest X-ray film, (8) afebrile and negative CRP, (9) absence of sinusitis and postnasal drip, or if present, they are proved not to be responsible for the cough, and (10) no other causes of cough such as heart disease, prescription of ACE inhibitors, current smoking. The results were as follows. 1) Many of the subjects were atopic, with positive skin tests to one or more common allergens in 10 subjects, elevated serum IgE in 4 subjects, and past history and family history of atopy in 4 and 7 subjects, respectively. 2) Respiratory infection preceded the onset of CVA in 3 subjects. 3) Cough was generally nocturnal, but 2 subjects coughed only in the daytime. 4) FEV1.0% was decreased (less than 70%) in only 2 subjects, whereas V25 was decreased (less than 80% of predicted value) in 11 out of 12 evaluable subjects, which suggested peripheral airway obstruction.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1507684 TI - [Experimental study on the role of prostaglandin D2 in the pathogenesis of bronchial asthma]. AB - Various kinds of chemical mediators have been implicated in the pathogenesis of bronchial asthma. PGD2 is a cyclooxygenase product which has various physiological effects. In this experimental study, we investigated the role of PGD2 in the pathogenesis of bronchial asthma. In a bioassay system, PGD2 caused dose-dependent contractile responses in non-sensitized guinea pig trachea and lung tissue strips. The subthreshold concentration of PGD2 in both strips was 25 ng/ml. Acetylcholine-induced contractile responses in both strips were significantly increased by continuous infusion of PGD2. In the experimental model of bronchial asthma, the levels of PGD2 were significantly increased in serum, bronchoalveolar lavage fluid (BALF) and lung tissue of sensitized guinea pigs after antigen challenge. We have also reported that the levels of PGD2 in BALF were elevated in patients with stable state bronchial asthma. These results suggest that PGD2 may be a key substance that increases airway responsiveness and induces asthmatic attacks. PMID- 1507685 TI - [The effect of oxygen administration on serum concentration of potassium during exercise]. AB - Recently, there have been many reports on the role of serum concentration of potassium as a potential limiting factor during exercise. K+ is known to induce muscle fatigue and to increase ventilation by direct stimulation of peripheral chemoreceptors. These two K(+)-mediated effects are considered to be the factors that limit exercise capacity. This effect seems to be exacerbated in hypoxemic states. The occurrence of hypoxemia in chronic pulmonary disease patients during exercise is believed to cause the excessive efflux of potassium to the extracellular space from skeletal muscles. The present study evaluated the relationship between the changes in arterial concentration of K+ and hypoxemia during exercise in 37 chronic pulmonary patients and 9 healthy controls. The study was carried out after obtaining formal and written consent of the patients in accordance with the stipulations of the Helsinki Declaration. Patients were divided into two groups according to PaO2 level at maximum exercise capacity; group I: PaO2 less than 55 torr, group II: PaO2 greater than or equal to 55 torr. The arterial concentration of K+ in group I patients tended to be higher than that in group II and controls. In group II, K+ concentration was significantly elevated (p less than 0.05) compared to controls. In group II, PaO2 values were inversely correlated with K+ (r = 0.3026; p less than 0.025), whereas in controls and group II they were unrelated. These results suggest that the augmented serum level of potassium in patients with chronic pulmonary disease is an important limiting factor during exercise. PMID- 1507686 TI - [Dyspnea and ventilatory muscle function during exercise on air and oxygen breathing in patients with chronic obstructive pulmonary disease (COPD)]. AB - Exercise performance and dyspnea in COPD patients have been shown to be improved with supplemental oxygen, although the exact mechanisms resulting in the improvement are still unclear. The purpose of the present study was to investigate a possible relationship between ventilatory muscle function and sensation of dyspnea (modified Borg Scale) during exercise on 20% O2 and 30% O2. Eight patients with COPD (FEV1 1.06 L +/- 0.30 L) exercised on a treadmill two times breathing compressed air or 30% oxygen with a one hour rest in between. The electrical activity of the diaphragm (EMGdi) was recorded with esophageal electrodes, and that of the sternomastoid muscle (EMGsm) was recorded from the fine wire electrodes. The ratio of high frequency (150 to 350 Hz) to low frequency (20 to 47 Hz) power (H/L) of EMGdi was analyzed to assess diaphragmatic fatigue, which was defined as a 20% fall of H/L ratio from the control value. Flow, volume, O2 Saturation (SaO2), esophageal pressure (Pes) and transdiaphragmatic pressure (Pdi) were measured. Tension time index (TTdi) was calculated from Pdi and the ratio of inspiratory time to total time for one cycle (Ti/Ttot). At rest, we measured maximal esophageal pressure (Pesmax), maximal transdiaphragmatic pressure (Pdimax), maximal integrated EMGdi (EMGdimax) and EMGsm (EMGsmmax). Incremental exercise was discontinued by dyspnea. The walking distance achieved was increased in all patients on 30% O2. Dyspnea and desaturation were significantly improved on 30% O2 breathing, and the onset of diaphragmatic fatigue was delayed.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1507687 TI - [A case of thyroid medullary carcinoma-like tumor of the lung with amyloid stroma]. AB - A 58-year-old man with history of productive cough and mild exertional dyspnea for several years was admitted to our hospital because of abnormal shadow on chest radiograph. Bronchofiberscopic examination revealed a polypoid tumor almost completely obstructing the right main bronchus. Bronchoscopic biopsy specimens showed amyloid-like deposits in the connective tissue surrounded by epithelium like tumor cells with squamous metaplasia, but no diagnostic findings. Malignant tumor was suspected and right upper lobectomy was performed. The surgical specimen revealed nests of tumor cells surrounded by amorphous eosinophilic substance, which was confirmed to include amyloid fibrils by electron microscopy. A few tumor cells contained argyrophil granules by Grimelius staining, and some showed PAP staining for calcitonin. There was no evidence of involvement of other organs including the thyroid gland during the four year postoperative follow-up period. This case was diagnosed as thyroid medullary carcinoma-like tumor of the lung, which is a bronchopulmonary carcinoid-related tumor. PMID- 1507688 TI - [A case of mediastinal lymphatic cyst possibly originating from the right thoracic duct]. AB - A 33-year-old male was admitted to our hospital because of an abnormal shadow in the right superior mediastinum on chest X-ray, which was first noted about half a year before his admission. Several diagnostic procedures, including fiber bronchoscopy, CT scan and MRI; however, no final diagnosis could be made. Thoracotomy was performed with the presumed diagnosis of benign mediastinal cystic tumor. Entry of the right thoracic duct into the cyst was observed at operation. Histological examination revealed that the cyst was lined by mono layered cuboidal epithelial cells with lymphocytic infiltration in the wall of the cyst. The mono-layered cuboidal epithelium of the thoracic duct gradually changed to the epithelium of the cyst. Twenty ml of colorless transparent fluid was aspirated from the cyst. Analysis of aspirated fluid revealed low concentration of several substances except LDH compared to the values of the previously reported normal standards and other reported cases. From these findings, the cyst was diagnosed as mediastinal lymphatic cyst. Entry of the thoracic lymphatic duct into the mediastinal lymphatic cyst is a rare occurrence, and it is of interest to speculate on its relationship to the origin of the lymphatic cyst. PMID- 1507689 TI - [A case of Hand-Schuller-Christian disease with pulmonary fibrosis]. AB - A 42-year-old man was admitted with dyspnea and abnormal shadows on chest roentgenogram, which showed bilateral reticulonodular shadows, multiple pulmonary cysts, and pleural effusion. A month after admission, he developed severe respiratory failure and chest X-ray revealed exacerbation of reticulonodular shadows. Steroid pulse therapy improved the symptoms and chest X-ray. He had atrophy of the mandible. Bone scintigram revealed multiple hot lesions. Bone biopsy of the right tibia showed lipogranuloma, and the diagnosis of Hand Schuller-Christian disease (HSC) was made. The percentage of OKT6-positive cells (Langerhans cells) found by immunofluorescence was 16.1% of all cells in bronchoalveolar lavage fluid, indicating pulmonary involvement due to HSC. This is a rare case of Hand-Schuller-Christian disease with pulmonary fibrosis. PMID- 1507690 TI - [A case of interstitial pneumonitis with hemoptysis, BOOP (bronchiolitis obliterans organizing pneumonia) pattern, granulomas and foreign body giant cells in lung biopsy]. AB - A 66-year-old male presented to our hospital in January 1990 with chief complaints of hemoptysis and cough. These symptoms had developed 10 months previously and had gradually increased. Fine crepitations were audible over the right lower lung field. There were no results suggesting an inflammatory process such as leucocytosis, elevation of ESR or positive CRP reaction. Chest X-ray film on the first visit showed fine nodular shadows in the right lower lung field, and chest CT revealed fine nodular shadows and mild dilatation of the right lower lobe bronchus. Transbronchial lung biopsy specimens showed granulomas with multinucleated giant cells, alveolitis and Masson bodies. The open lung biopsy specimens showed numerous macrophages and foreign body giant cells, and extensive organizing exudates in the bronchioles and alveolar spaces. Proliferation of smooth muscle and fibrosis around the dilated bronchioles were also seen. Thus, this patient demonstrated BOOP pattern, with granulomas and foreign body giant cells. His hemoptysis appeared to have resulted from inflammation of dilated bronchioles. His symptoms and abnormal shadows on chest X-ray improved without any therapy after admission. After treatment with corticosteroid, the diffuse fine nodular shadows disappeared. There has been no recurrence of symptoms to date, although this patient has continued living in the same environment as prior to admission. BAL findings during his prolonged follow-up revealed decrease in lymphocytes and elevation of CD4/CD8 ratio. Although the presence of granulomas suggests the possibility of an allergic reaction, no antigenic material could be identified in this case.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1507691 TI - [A case of humidifier lung associated with BHL]. AB - We encountered a rare case of hypersensitivity pneumonitis associated with bilateral hilar lymphadenopathy (BHL). The patient was a 53-year-old male, who developed dry cough and shortness of breath when using a humidifier since 1982. He was admitted to our hospital for further evaluation in 1987. Chest X-ray films showed BHL and ground glass appearance in the bilateral lung fields. Pulmonary function test indicated disturbance of diffusing capacity. Transbronchial lung biopsy revealed interstitial pneumonitis, and lymph node biopsy by mediastinoscopy showed lymphoid sinus histiocytosis without noncaseating granuloma. Provocation test using the humidifier was positive, and the diagnosis of humidifier lung with BHL was made. PMID- 1507692 TI - [A case of isolated absence of the right pulmonary artery]. AB - A 40-year-old woman was admitted to our hospital for investigation of an abnormal chest roentgenogram. She had been well with normal exercise tolerance and had no history of pneumonia. The chest roentgenogram showed decreased vascularity of the right lung, ipsilateral small hemithorax, and shift of the mediastinum toward the right. In the right lung field, hazy and confluent micronodular shadows were seen, and the left lung was emphysematous and hyperlucent. Herniation of the left lung into the contralateral thorax was seen. Although lung perfusion scintigrams showed no detectable blood flow to the right lung, a krypton ventilation study revealed diminished but homogeneous ventilation of the ipsilateral lung. A bronchogram showed normal structure of the bronchi. Cardiac catheterization revealed normal pulmonary arterial pressure. A pulmonary angiogram showed no right pulmonary artery, and absence of other cardiovascular anomalies. Therefore, the diagnosis of isolated absence of the right pulmonary artery was confirmed. An aortic angiogram demonstrated collateral vessels originating from one of the bronchial arteries, the infradiaphragmatic artery, and the right coronary artery. Chest CT disclosed cystic changes in the right lung field. PMID- 1507693 TI - [A case of bronchiolitis obliterans organizing pneumonia in a patient with rheumatoid arthritis who responded to corticosteroid and immunosupressant therapy]. AB - A 56-year-old man with rheumatoid arthritis was admitted to our hospital with dyspnea on exertion, fever and right chest pain. Chest X-ray showed bilateral, predominantly lower interstitial shadows and right pleural effusion. Open lung biopsy specimen showed bronchiolitis obliterans organizing pneumonia (BOOP) with prominent alveolitis, and corticosteroid therapy was introduced. Because the patient showed little response to corticosteroids, an immunosupressant (cyclophosphamide) was added. There was marked clinical, physiological and roentgenographic improvement in response to combined therapy. The therapeutic response of some BOOP patients seems to vary according to its pathogenesis and pathological findings, and these should be taken into consideration in the selection of therapeutic strategies. PMID- 1507694 TI - [A case of bronchogenic cyst in the subdiaphragmatic region]. AB - A surgical case of subdiaphragmatic bronchogenic cyst is presented. A 44-year-old female was admitted because of a radiological abnormality of a mass lesion at the left diaphragm. Laboratory examinations did not reveal any significant abnormalities. Chest CT revealed the mass lesion with smooth margin, whose density was higher than that of water. Both MRI T1-weighted and T2-weighted images showed a relatively high intensity of the mass. On endoscopic ultrasonography, the lesion consisted of a thin wall with highly echoic contents, and its shape changed during respiratory movement. On the basis of the findings of these imaging modalities, the diagnosis was considered to be bronchogenic cyst. The mass was resected via laparotomy, and its histologic diagnosis was bronchogenic cyst containing turbid fluid. Subdiaphragmatic bronchogenic cyst is reported rarely. The characteristic findings of CT, MRI and endoscopic ultrasonography enable the diagnosis of a cyst with turbid contents. PMID- 1507695 TI - [Diffuse large cell lymphoma with spontaneous regression in the lung and lymph nodes. Case report]. AB - An 84-year-old woman was admitted to our hospital because of swelling of the cervical lymph nodes and multiple tumorous lesions observed on radiographic studies. Transcutaneous lung biopsy was performed, but necrosis of the tissue was too marked to make a diagnosis. The diagnosis of diffuse large-cell lymphoma was made based on a biopsy of the pretracheal lymph node. During the first two months after admission, the left cervical lymph nodes and most of the pulmonary lesions regressed not withstanding of special treatment for lymphoma. The patient eventually died of generalized peritonitis. At autopsy, metastasis of systemic organs by malignant lymphoma was observed. Most of the lung regions were cicatrized, but clusters of atypical lymphocytes were observed in the necrotic tissue. The tumor in the mucosa of the small intestine showed necrosis, which accounted for the intestinal perforation. The total clinical course after admission was about six months. Spontaneous regression of diffuse large cell lymphoma is rare, and this is the second reported case in Japan. PMID- 1507696 TI - [Inhibitory effect of amlexanox on asthmatic attacks in an aspirin sensitive asthmatic]. AB - The anti-allergic action of amlexanox is reported to be associated with inhibition of the release of LTC4, LTD4 and histamine, and with antagonistic activity on leukotrienes. The patient was a 18-year-old female who had suffered from bronchial asthma since the age of fifteen. We diagnosed the case as aspirin sensitive asthma because of development of a severe asthmatic attack with syncope after oral administration of an analgesic for treatment of a common cold at the age of seventeen. She also had sensitivity to toothpaste. Three-minute aerosol inhalation challenge with 0.1, 1 and 10% solution of sulpyrine was performed as a stepwise increment at 20 minutes intervals. This inhalation test was positive and it evoked simultaneous increases of LTC4, LTD4 and histamine in the peripheral blood. Since the commencement of oral administration of 150 mg per day of amlexanox, the patient has had no attacks for about 8 months. In the second inhalation test, premedication with amlexanox elevated the threshold of sulpyrine and inhibited the release of LTC4, LTD4 and histamine. We report that amlexanox was of use to control asthmatic attacks in this aspirin-sensitive asthmatic patient. PMID- 1507697 TI - [A case of invasive thymoma responsive to preoperative chemotherapy]. AB - A 38-year-old male was admitted with edema of the neck and face. Chest X-ray revealed a mediastinal tumor. On chest CT and MRI, a tumor infiltrating the superior vena cava and bilateral brachiocephalic veins in the upper mediastinum was observed. Venography revealed obstruction of bilateral brachiocephalic veins. The tumor was diagnosed as thymoma by percutaneous biopsy, but since it was of stage III according to Masaoka's classification, complete extirpation was considered to be impossible. Preoperative chemotherapy with multiple drugs (CDDP, ADM, VCR, CPA) was administered. The superior vena cava syndrome resolved and the tumor diminished in size. Because of leukopenia, rhG-CSF was also used. The tumor infiltrated the left brachiocephalic vein; therefore, total resection and left brachiocephalic vein reconstruction were performed. Histopathological examination showed extensive, necrosis and fibrosis containing residual thymoma. Postoperatively, similar chemotherapy and cobalt irradiation (40 Gy) to the superior mediastinum were performed. We thus present a case of invasive thymoma which responded to preoperative chemotherapy. PMID- 1507698 TI - [Diseases and operative modes of tracheobronchoplasty]. AB - In 251 patients of tracheobronchoplasty, the disease distribution and the indicative expansion were analysed. The largest series was lung cancer encountered in 49%, followed by thyroid cancer in 20%, posttracheostomy tracheal stenoses, primary tracheobronchial tumors, and tuberculosis in 7-8% respectively, and others in remaining 4%. In lung cancer, two way of operative modes have been tried, which were carinal resection extensively and sleeve or wedge segmentectomy limitedly. Laryngotracheal anastomosis increased applicable cases in thyroid cancer and posttracheostomy subglottic stenosis. Preoperative irradiation for adenoid cystic carcinoma increased the cases for operation. A new carinal reconstruction via the subaortic arch approach for tuberculous stenosis was successfully underwent. End-to-end anastomosis instead of partial suture was advisable in the early stage of traumatic bronchial rupture. Congenital airway malformation is a disease to be divised some operations which might furthermore increase operative modes. In summary, 38 operative modes have been experienced so far, and these might increase in number depending to diseases. PMID- 1507699 TI - [Endoscopic surgery of airway lesions by Nd-YAG laser treatment]. AB - Between April 1980 and November 1990, we treated 212 cases of airway lesion using an Nd-YAG laser via the fiberoptic bronchoscope. The Nd-YAG laser power output was usually 40 W (20-60 W) delivered in 2 sec. shots. The cases consisted of 98 primary lung cancer, 12 primary tracheal cancer, 53 metastatic airway lesion, 7 benign tumor, and 42 cicatricial and granulomatous lesions. The therapeutic effects of Nd-YAG laser treatment were evaluated based on alleviation of dyspnea, widening of airway, and curative vaporization for therapeutic purposes. Effectiveness was observed in 180 of a total of 212 cases (84.9%). Out of 75 emergency cases in which a lifesaving procedure was performed to widen the airway, effective results were obtained in 70 (93.3%) with dramatic improvement in condition. It was also effective in 90 of 109 cases (82.6%) in which the procedure was performed for staged (palliative) widening of airway. In 55 cases of advanced lung cancer (Stage III or IV, mainly non-small cell cancer) in which palliative widening procedure was performed, one year survival was 44%. In 13 of 18 cases (72.2%) in which the procedure was performed for curative vaporization of invasive cancer, successful results were obtained. In 7 cases of benign tumor in which vaporization was performed as a radical curative procedure, no recurrence was observed in any cases. In 53 cases of metastatic airway lesion, effective results were obtained 48 (90.6%). The primary lesions of these cases consisted of 14 cases of esophageal cancer, 9 cases of lung cancer, 7 cases of colo-rectal cancer, 7 cases of thyroid cancer, and 16 others.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1507700 TI - [A clinical assessment of efficacy in continuous retrograde cerebral perfusion method]. AB - From November 1990 to June 1991, 8 patients underwent surgical repair using continuous retrograde cerebral perfusion (CRCP). We evaluated the effect of CRCP from these 8 cases. As a method of CRCP, we perfused with oxygenated blood from SVC canulae with a internal jugular vein pressure of 30-40 cmH2O. Simultaneously systemic perfusion from femoral arterial canulae was performed. At nasopharyngeal temperature of 15-21 degrees C, CRCP time was 46-115 minute. SVC perfusion flow was 280-900 ml/min, and femoral arterial perfusion flow was 450-1,200 ml/min. At 30 minute after starting CRCP, oxygen tension of the blood which was returned to aortic arch was 11-23 mmHg, whereas oxygen tension of the SVC perfusion blood was 210-398 mmHg. In only one patient, transient involuntary movement was seen after operation, but prolonged emergence from anesthesia was not seen. In conclusion, CRCP is considered as an useful method in the operation of the aortic arch. PMID- 1507701 TI - [Clinical experience of continuous retrograde cerebral perfusion for assisted circulation during the surgical treatment of acute dissection of aorta: Stanford A type]. AB - Surgical treatment of the dissection involving the ascending aorta or aortic arch represents one of the most complicated technical challenges. Recently continuous retrograde cerebral perfusion (CRCP) is sometimes applied in order to avoid cerebral complications. We compared two surgical groups, one of which was performed graft-replacement of ascending aorta using CRCP and another was utilized normograde cerebral circulation, about the technique of operation, total extracorporeal circulation (ECC) time, aortic clamp time, separate ECC time, total bleeding volume, and urination during operation. In the group using CRCP, separate ECC time was 53 min (mean), and intraoperative bleeding volume was only 1,170 ml. Good urination was obtained during operation. Postoperative courses were uneventful, and consciousness was smoothly and soon recovered. The new method of separate ECC has some advantages over the previously described methods, particularly for avoidance of cerebral complications. As it is not necessary to require dissecting, taping, and clamping of cephalic branches, operative procedure will be very simplified, easier and safer, leading to intraoperative bleeding is a fewer. It is our belief that this method should be widely applied in the operation of graft-replacement of ascending aorta or aortic arch in the near future. PMID- 1507702 TI - [Evaluation of calcified ascending aorta by thoracic computed tomography and technical pitfall for coronary artery bypass grafting]. AB - The cumulative 94 coronary bypass patients were evaluated on calcification of the ascending aorta preoperatively by computed tomography (CT). CT demonstrated the calcification of the ascending aorta in 12 patients (12.8%). In these patients with severely calcified ascending aorta, we performed femoral cannulation (6 cases), distal anastomosis without aortic cross clamp (2 cases), proximal anastomosis through single aortic cross clamp (3 cases) and non proximal anastomosis to use arterial conduits (3 cases). In this series, we did not have any embolic episode. The thoracic computed tomography is effective for evaluation of calcified ascending aorta and in this situation, operative modifications are necessary for obviation of stroke. PMID- 1507703 TI - [Result of surgical treatment of true or dissected thoracic aneurysm: determinants analysis in operative mortality and morbidity]. AB - Between 1986 and 1990, 69 patients underwent surgery either for thoracic aneurysm (27 patients) or aortic dissection (42 patients). Sixty one patients (88%) survived and 8 patients (12%) died after surgery. Main determinants of deaths in 4 patients with true arch aneurysm were bleeding from the sites of aortic clamping or anastomosis and intraoperative severe LOS. Three patients with acute type A dissection died from bleeding due to clamp injury or myocardial ischemia. The cause of death in the patient with chronic type B dissection was associated with brain damage due to hypoxia developed during left heart bypass. Postoperative cardiac, pulmonary, hepatic and renal functions were analyzed in the operative survivors. Cardiac functions were maintained well in all patients except two patients with chronic type A dissection. Four patients, one with true arch aneurysm, 2 with chronic type A and one with chronic type B dissection, required tracheostomy. The mean of maximum total serum bilirubin exceeded 4 mg/dl in the patients with true arch aneurysm, acute and chronic type A dissection. The level of serum creatinine showed slight increase in all patients but prophylactic peritoneal dialysis was performed in one patient with chronic type A dissection. In conclusion, the cause of deaths in most patients with thoracic aneurysm was due to inappropriate operative techniques and circulatory supports during surgery. Without the complication described above, the patients could tolerate surgery well. PMID- 1507704 TI - [A new hemodynamic diagram, using COP-PCWP and CI as parameters, after open heart surgery]. AB - In 24 patients subjected to cardio-pulmonary bypass (CPB) operation, changes in colloid oncotic pressure (COP), cardiac index (CI), respiratory index (RI), and pulmonary capillary wedge pressure (PCWP) were measured within a 48 hour period. The patients were divided into two groups according to dose levels of catecholamine. In 18 patients received small catecholamine doses, a stable hemodynamic and respiratory status were maintained. However, 6 patients received catecholamine doses of more than 15 micrograms/kg/min exhibited low COP, low CI, high RI and high PCWP. In this study we designed a new hemodynamic diagram using COP-PCWP and CI as parameters of the cardiac function. We consider that these parameters are more suitable than Forrester's parameters to evaluate the patient's condition before and after open heart surgery. PMID- 1507705 TI - [Coronary bypass surgery using arterial conduit and its pitfall]. AB - Three patients with spasm of internal mammary arteries and gastroepiploic artery immediately after coronary bypass surgery were reported. On completion of the revascularization, all patients could not be weaned from cardiopulmonary bypass. The flow velocity waveforms of the arterial grafts measured by pulsed Doppler velocimeter showed only small systolic component without diastolic flow and the palpation revealed profound spasm partially in the arterial conduits. Although all patients could be weaned from cardiopulmonary bypass only after insertion of a saphenous vein graft, two of them died on the next day. In all patients, free flow measured prior bypass was considered to be sufficient and a technically satisfactory anastomosis was felt to be performed. If a profound hemodynamic instability as a result of intractable spasm of arterial conduit occurred after completion of coronary bypass surgery, an additional saphenous vein graft should be placed before discontinuation of cardiopulmonary bypass. PMID- 1507706 TI - [A new balloon electrode for intraoperative endocardial mapping]. AB - To enhance the utility of epicardial mapping in the intraoperative determination of the location of the arrhythmic source, we developed a new balloon electrode covered with Presnet-tubular dressing material including 46 snap electrode recording sites. The bipolar recording sites, 1.0 mm in diameter and spaced at intervals of 1.5 mm, are constructed of gold and directly attached steel wire. This new balloon electrode was effective intraoperative determination of the lesion in 2 patients one with Wolff-Parkinson-White syndrome and the other with ventricular tachycardia. PMID- 1507707 TI - [Transatrial approach to provide exposure of the left atrium]. AB - Surgical exposure of the left atrial structures including the mitral valve apparatus is occasionally problematic, when the left atrium is small or noncompliant in the presence of previously implanted aortic prosthesis. We operated eleven cases with an incision that is a modification of a maneuver proposed by Dubost and colleagues, and all but one provide an excellent exposure of the left atrium and mitral valve apparatus. In one case of combined valvular disease complicated by chronic pericarditis, operative view was not satisfactory. The preserves equine pericardial patch was utilized to close the incision in 5 cases. No serious arrhythmias as atrioventricular conduction block was experienced. With this maneuver, the application is recommended to provide excellent exposure into the left atrium and mitral valve apparatus. PMID- 1507708 TI - [An experience of surgical treatment for catamenial pneumothorax with diaphragmatic and pulmonary endometriosis]. AB - A case of catamenial pneumothorax with diaphragmatic and pulmonary endometriosis is presented. A 43-year-old, married woman had three times of recurrent right pneumothorax during the period from January to July on 1990. Each episode was apparently related to the onset of the menstruation suggesting catamenial pneumothorax. Right thoracotomy revealed a perforation of the diaphragm and five black spots on the visceral pleura. Involved portion both diaphragm and lung were excised. Microscopic examination of the excised specimens showed endometrial stroma in the diaphragm and subpleural layer of the lung. Although it has been postulated that intrathoracic endometriosis is a possible cause of the pneumothorax, very few cases have been reported in which pulmonary or pleural endometriosis was demonstrated histologically. Surgical and pathologic findings are documented discussing the relationship of both conditions in this report. PMID- 1507709 TI - [Bochdalek diaphragmatic hernia in the elderly: a case report]. AB - We successfully treated surgically an elderly patient, a 80-year-old woman, with Bochdalek diaphragmatic hernia. She had intermittent episodes of intestinal obstruction. A preoperative chest roentgenograph revealed a loop of gas-filled bowel in the left chest and elevation of the left diaphragm. CT scanning of the thorax revealed the bowels filled with gastrografin in the left thoracic cavity. She was treated surgically, through transabdominal and then transthoracic approaches. The herniated large bowel was reduced from the thoracic cavity and the hernial sac was excised. The posterolateral defect of the diaphragm, 5 x 6 cm in size was closed with interrupted mattress sutures. The patient has been well without any symptoms 6 months after the surgery. Bochdalek diaphragmatic hernia is the most common problem in infants with risky respiratory distress and high mortality, however it is preferable to carry out surgical treatment for adult patients because of good postoperative results. As a surgical route in the management of Bochdalek diaphragmatic hernia in adults, a transthoracic approach is preferable since it provides easy separation and reduction of herniated bowels from the thoracic cavity and easy closure of the diaphragmatic defect, furthermore there are no other serious gastrointestinal complications which are required specific repair. PMID- 1507710 TI - [A case of so-called carcinosarcoma of the lung]. AB - A 65-year-old male was admitted to our institute because of bloody sputum. A tumor in right S6 was detected by X-ray, CT and MRI. Bronchoscopic study showed that the right lower bronchus was occluded by the tumor, in which non-epithelial malignant cells were detected. Therefore right bilobectomy was performed. This tumor was a pedunculated endobronchial type measuring 6 x 4 x 3cm. Histologically, the tumor presented carcinomatous (squamous cell carcinoma and adenocarcinoma) and sarcomatous elements. Immunohistologically, many malignant cells were positively stained by vimentin and muscle-actin, which suggested differentiation from muscle components. PMID- 1507711 TI - [A case of paraesophageal bronchogenic cyst with esophageal communication]. AB - A case of mediastinal bronchogenic cyst communicating with the esophagus was reported. Previously, only 2 cases have been reported in the available literature. A 34-year-old man was admitted with a cystic mass communicating with the esophagus which was demonstrated on a barium study. Operation was performed with a suspect of esophageal diverticulum or congenital cyst with esophageal communication. At right thoracotomy, a mass measuring 6.0 x 5.0 cm with a well defined patent communication to the esophagus was resected. It was a monolocular cyst containing a small amount of viscous mucus. Histologically, the cyst lined by a ciliated columnar epithelium, and it was diagnosed as a bronchogenic cyst because of the presence of the mucous glands, smooth muscle tissue and cartilage. This is the first case report of mediastinal bronchogenic cyst with esophageal communication appeared in the Japanese literature. PMID- 1507712 TI - [A case report of solitary bone cyst of rib detected from pathological fracture]. AB - A case of solitary bone cyst of rib was reported. The patient was 28-year-old man who was admitted to our hospital complaining of chest pain caused by pathological fracture of the left 10th rib. Chest x-ray film revealed a solitary cystic lesion of the 10th rib. The tumor was removed by extrapleural rib partial resection and the histological examination confirmed the diagnosis of solitary bone cyst. PMID- 1507713 TI - [A case of a right subclavian arterial aneurysm associated with the aortic arch anomaly in childhood]. AB - Aneurysms in the subclavian arteries are extremely rare in childhood. A 7-year old boy was admitted with hoarseness and abnormal shadow in the chest film. Radiologic studies demonstrated a right subclavian arterial aneurysm associated with the aortic arch anomaly. Proximal and distal ligation of the subclavian arterial aneurysm and reconstruction of blood flow by an aorto-subclavian bypass using a 5 mm GORE-TEX prosthetic graft were performed through a standard median sternotomy incision with extension to the right supraclavicular space. The postoperative course was uneventful and he was discharged in 3 weeks. The literature of the subclavian arterial aneurysm was briefly reviewed. PMID- 1507714 TI - [Surgical management of desmoid tumors of the chest wall: a case report and review of literature]. AB - A 45-year-old man without special predispositions showed a chest wall tumor with tenderness. A needle biopsy revealed a desmoid tumor which had invaded the muscles. A wide resection from the second to fifth rib was carried out and 4 years have passed without recurrence. A resection, at least 3 cm away from the lesion, is necessary for desmoid tumors which seem to have clear margins. PMID- 1507715 TI - [Closure of ventricular septal defect of interrupted aortic arch with left ventricular outflow obstruction]. AB - Leftward shift of the infundibular septum (IS) in interrupted aortic arch (IAA) with ventricular septal defect (VSD) often develops significant left ventricular outflow obstruction (LVOTO). Seven-day-old boy with 2.6 kg body weight underwent the two-stage operation for this anomaly. The aortic arch was interrupted between the left common carotid and the left subclavian artery. At the first stage, a 5 mm GORE-TEX graft was used to connect the interrupted arch, and pulmonary artery banding was performed. In closure of VSD at the second stage, IS was penetrated by stitches for the VSD patch to left ventricular outflow tract. IS with leftward shift could be pulled toward right ventricular side with patch fixation and LVOTO was prevented by this method. PMID- 1507716 TI - [A case of ischemic mitral regurgitation treated by mitral annuloplasty (MAP) and coronary artery bypass grafting (CABG)]. AB - A 79-year-old woman with a previous history of myocardial infarction, suffered acute myocardial infarction again. A coronary angiogram revealed triple vessel disease, and a left ventriculogram showed severe mitral regurgitation. The patient fell into cardiogenic shock after cardiac catheterization, and IABP was started. She underwent MAP and saphenous vein bypass grafting to the left anterior descending coronary artery and left circumflex coronary artery. Although the postoperative course was complicated by acute renal failure and respiratory dysfunction, the patient recovered from the operation and was discharged on the 137th postoperative day. Since the operative mortality of conventional valve replacement combined with CABG in ischemic mitral regurgitation has been high, we preferred MAP for this case. PMID- 1507717 TI - [A case of myocardial infarction with normal coronary arteriogram in combined valvular disease]. AB - In this report, we presented a case of myocardial infarction with angiographically normal coronary artery, possibly caused by coronary thromboembolism due to combined mitral and aortic valvular lesions. Embolism arising from the mitral valve or left atrium might preferentially enter the coronary arteries because of the turbulence produced by the associated aortic valve lesion. Her impaired cardiac function, due to valvular lesions and myocardial infarction, has improved after double valve replacement. PMID- 1507718 TI - [A case of simultaneous operation of coronary artery bypass and ascending aorta to bifemoral bypass for ischemic heart disease combined with bilateral leg ischemia]. AB - A 58-year-old man was admitted to our hospital because of angina pectoris with severe intermittent claudication. Angiography showed triple-vessel disease of the coronary artery and complete obstruction of the bilateral common iliac arteries from their origins. Both femoral arteries were patent by collateral supplies. Combined revascularization of coronary and femoral arteries was performed. Coronary arteries were bypassed with in situ left internal thoracic artery, gastroepiploic artery and saphenous vein graft. Bilateral femoral arteries were bypassed with externally supported Dacron graft from ascending aorta through the preperitoneal space. The patient recovered well and postoperative angiography revealed all bypass grafts patent. PMID- 1507719 TI - [A case report of replacement of the extracardiac conduit for tetralogy of Fallot: reconstruction with autogenous tissue around the conduit]. AB - Replacement of the valved extracardiac conduit with autogenous tissue was performed on a 13-year-old female. The procedure was based on that reported by Danielson in 1987. She underwent the first operation for tetralogy of Fallot with pulmonary atresia using a valved extracardiac conduit (#16 mm Bjork-Shiley valve) 8 years ago. Recently, she complained exertional dyspnea and chest pain. Reoperation was scheduled because of bleeding tendency, somatic growth of the patient, and severe distal anastomotic stenosis of the conduit by right ventriculogram. At operation, the valved conduit was removed under cardiopulmonary bypass, and autogenous connective tissue around the conduit was preserved as the posterior wall of the new conduit. An onlay patch (pericardial monocusp patch) was sutured to form the roof of the new tract. Postoperative catheterization showed no residual stenosis or pressure gradient between the right ventricle and the pulmonary artery. This technique is useful as the replacement of extracardiac conduit because of its simplicity, no necessity of postoperative anti-coagulant therapy, and possibility to make a generous-sized new outflow tract. PMID- 1507720 TI - [Intratesticular cell to cell interaction]. PMID- 1507722 TI - [Experimental and clinical study of intravesical BCG therapy. The role in the prevention of recurrence of superficial bladder tumor]. AB - The effects of Tokyo strain bacillus Calmette-Guerin (BCG), which is available in Japan for treatment, were studied in an experimental murine bladder tumor (MBT-2) model prior to clinical study for treatment of superficial bladder tumor. The results were as follows: Tokyo-strain BCG is more effective on the local injection around the tumor than on systemic administration. BCG therapy is more effective at earlier time of small tumor burden. BCG also has a prophylactic effect against the tumor growth. Clinical trial of intravesical instillation of BCG was performed on patients with superficial bladder tumor for prophylaxis of tumor recurrence after transurethral resection of the tumor. In patients of 145 primary cases, the tumor recurrence rate after BCG therapy was estimated, comparing with that of historical control in our department. The historical control groups are consisted of 50 patients who were treated by some intravesical chemotherapy after TUR and 38 patients, who were treated by TUR alone. The tumor recurrence rate in BCG group was significantly lower than that in both control groups. No relationship between PPD responsiveness and the tumor recurrence rate could be detected. On the other hand, in the patients of 36 recurrent cases, evaluation was performed by the tumor recurrence rate comparing with those during the two years prior to BCG therapy. The results demonstrated a statistically significant decrease in recurrent tumor following BCG therapy. Although most of the adverse effects in this study such as bladder irritability, flu-like syndrome and macroscopic hematuria were minimal and tolerable. There were no significant side effects or serious complications attributable to BCG therapy in this series. These results indicate that intravesical Tokyo strain BCG instillation provide prophylactic effects against recurrence of superficial bladder cancer. PMID- 1507721 TI - [Relationship between extent of bone metastases and effect of endocrine therapy evaluated with bone scintigraphy in stage D2 prostatic cancer]. AB - Bone scintigraphy of metastatic lesion on 128 patients with prostatic cancer were classified according to the proposal by Soloway et al (Cancer, 61; 195-202, 1988). Since all patients received endocrine therapy, the response to therapy and survival were examined in relation to bone lesion. In extent of disease (EOD) 1, main metastatic lesions were located in the pelvis, lumbar spine, and with increasing number of EOD, metastases in the upper spine, rib, and skull appeared. Longer survival were noticed in EOD 1, followed by EOD 2 and EOD 3, and EOD 4 revealed the shortest survival. The survival of EOD 2 was similar to thus of EOD 3. However, when grades of tumor were considered, moderately differentiated cancer showed longer survival than poorly differentiated cancer in EOD 2 and EOD 3. The response as assessed by bone scintigraphy following 6-month therapy was well correlated with the number of EOD. When individual items for evaluation of response were examined, the results of local response of the prostate and values of PAP showed good correlation with survivals, however, that of bone lesions with bone scintigraphy failed to show such a correlation with prognosis. Therefore, it is concluded that the therapeutic evaluation of bone lesions with bone scintigraphy is difficult to interpret 6 months after initiation of treatment. PMID- 1507723 TI - [Implantation of self-contained non-inflatable penile prosthesis in patients with organic impotence]. AB - Between April, 1988 and August, 1990, the OmniPhase penile prosthesis, a non inflatable self-contained penile prosthesis, was implanted in 34 patients, aged from 37 years to 79 years, averaging 54.2 years. The etiologies of the impotence were radical surgery for bladder cancer or rectal cancer in 17 patients, diabetes mellitus in 7 patients, vascular abnormality in 3 patients, spinal injury in 2 patients, penile disorders in 2 patients and others in 3 patients. Penile prosthesis was implanted by subcoronal incision under spinal or general anesthesia. Clinical results were evaluated 12 weeks after surgery. Thirty-two patients (94.1%) could have intercourse postoperatively. Eighteen patients (52.9%) were completely satisfied and 14 patients (41.2%) were satisfied, whereas one patient (2.9%) had no improvement and another patient (2.9%) deteriorated. There was no serious complication. However, prosthesis was explanted because of skin erosion in one patient. Pain, which lasted for more than 10 days, was seen in 3 patients (8.8%), penile edema in 11 patients (32.4%), and acute epididymitis in one patient. The obtained results showed that implantation of OmniPhase penile prosthesis is a safe and useful procedure for treatment of organic impotence. PMID- 1507724 TI - [An electromyographic study of the feline urethral rhabdosphincter in the normal state and after sacral rhizotomy. Part 1. Characteristics of action potentials of the rhabdosphincter and micturition and continence reflexes]. AB - To investigate functional property of the urethral rhabdosphincter, the male feline rhabdosphincter was examined by means of electromyography using fine electrodes. Experiments were performed on 28 normal (N group) and 13 rhizotomized cats under chloralose anesthesia, the latter being further divided into two groups: 4 cats of 1-3 weeks (SR group) and 9 cats of 10-24 weeks (LR group) after complete sacral rhizotomy. Frequency of action potentials of the rhabdosphincter at empty bladder in N, SR and LR group was 1.8 +/- 0.3, 16.4 +/- 2.0, 8.9 +/- 1.4 spikes/sec, respectively, with significant difference between N and the other two groups and also between SR and LR group. Spontaneous discharges of the rhabdosphincter in SR and LR group were not abolished after neuromuscular junction blockade. The duration of action potentials of the rhabdosphincter in N, SR and LR group was 3.34 +/- 0.08, 1.71 +/- 0.07, 1.72 +/- 0.04 ms, respectively, with significant difference between N and the other two groups. Micturition reflex was negative in both SR and LR groups, but in 7 cats of LR group with dorsal roots preserved, activities of the rhabdosphincter increased reflexly by vesicourethral or urethrourethral contraction reflex, while they did not in 2 cats of LR group without preservation of dorsal roots and in SR group. Bulbocavernosus reflex was negative in both SR and LR groups.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1507725 TI - [An electromyographic study of the feline urethral rhabdosphincter in the normal state and after sacral rhizotomy. Part 2. Responses of the rhabdosphincter to hypogastric nerve stimulation]. AB - To investigate functional aspect of sympathetic innervation of the urethral rhabdosphincter, responses of the male feline rhabdosphincter to hypogastric nerve (HGN) stimulation were examined by means of electromyography using fine electrodes. Experiments were performed on 28 normal (N group) and 13 rhizotomized cats under chloralose anesthesia, the latter being further divided into two groups: 4 cats of 1-3 weeks (SR group) and 9 cats of 10-24 weeks (LR groups) after complete sacral rhizotomy. HGN stimulation (1 Hz, 0.3 ms pulse duration, 2 30 V) elicited responses of the rhabdosphincter in N and LR groups. In N group, HGN stimulation still elicited responses of the rhabdosphincter even after pudendal nerve was transected in advance, indicating that these evoked potentials were independent of somatic nerve inflow. The threshold stimuli and latencies of the evoked responses in N group (3.0 +/- 0.2 V, 81.7 +/- 5.7 ms, respectively) were not significantly different from those in LR group (2.9 +/- 0.3 V, 71.5 +/- 10.5 ms), but the amplitudes of the evoked responses were significantly larger in LR group than in N group (110 +/- 12 vs 18 +/- 2 microV, p less than 0.001). These evoked responses of the rhabdosphincter were resistive to prazosin (0.2 mg/kg) and atropine (0.5 mg/kg), but were abolished by hexamethonium (2 mg/min, 10-25 mg) and pancuronium (0.1-0.3 mg/kg) in both groups. In N group, repetitive stimulation (10-20 Hz) of HGN increased activities of the rhabdosphincter when the bladder was empty, but not when the bladder was full enough to trigger the vesicourethral relaxation reflex.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1507726 TI - [Vesical ultrasonography and internal examination of female patients with urethral syndrome]. AB - Transabdominal ultrasonography of the bladder and internal examination were performed in 80 female patients without pyuria. They were divided into 3 groups: urethral syndrome with trigonitis (49 cases), asymptomatic trigonitis (16 cases) and normal bladder (15 cases) by cystoscopy. Ultrasonography of trigonitis with or without symptoms showed focal dilation of the submucosal low echo zone and mucosal irregularity around the bladder neck. On the sagittal view, the thicknesses from the surface of mucosa to that of muscle layer within 2 cm from the bladder neck were 4 +/- 1 mm (mean +/- standard deviation) in the group with urethral syndrome and in that with asymptomatic trigonitis, and 3 +/- 1 mm in the normal bladder group. Mucosa of the trigonitis with or without symptom is patients with significantly thicker than that of those with normal bladder (p less than 0.01). On internal examination, tenderness at the upper frontal wall of the vagina was present in 10 of 11 cases (91%) with urethral syndrome, in 2 of 8 cases (25%) with asymptomatic trigonitis and in one of 9 cases (11%) with normal bladder. There was a significant difference (p less than 0.005) between the degree of inflammation and the number of cases with tenderness at the frontal wall of the vagina. From these results, transabdominal ultrasonographic measurement of mucosal thickness around the bladder neck and internal examination for tenderness at the frontal wall of vagina are thought to be useful methods for diagnosis and follow-up of urethral syndrome.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1507727 TI - [The pathogenesis of hypercalciuria from the aspect of the response to human parathyroid hormone in Ca containing stone formers]. AB - In order to clarify the pathogenesis of hypercalciuria, the response to extrinsic human parathyroid hormone (h-PTH) was studied the 21 patients with calcium containing urinary stone(s) and 5 normal controls (NO). The stone patients were classified into 3 groups from the result of the oral calcium loading test, i.e. Non-hypercalciura (NH, n = 8) and absorptive hypercalciuria (AH, n = 8) and renal hypercalciuria (RH, n = 5). Only in the AH group, urinary excretion of calcium (u Ca) was strongly correlated to that of sodium (u-Na) in pre-load of h-PTH, and both increments were also correlated in post-load of h-PTH. As of this fact the increase in Na excretion seems to be responsible for a cause of hypercalciuria in the AH group. There was a significant correlation between the value of %TRP in pre-load of h-PTH and the rate of urinary phosphorus (P) increment between pre load and post-load of h-PTH in the NO and NH groups. However, this relationship was not found in the AH and RH groups. These findings indicate that there is response disorder of P to h-PTH. In addition, serum P was low, plasma 1,25 (OH)2D was high, N-c-AMP was low in the AH group, whereas both serum P and %TRP were low in the RH group in pre-load of h-PTH. These findings are compatible with the primary renal P leak.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1507728 TI - [Studies on the production of endogenous cytokines in patients with renal cell carcinoma]. AB - This study was undertaken to determine the production of tumor necrosis factor (TNF) and interferon-gamma (IFN-gamma) by biological response modifier (BRM) in patients with renal cell carcinoma (RCC). Peripheral blood mononuclear cells (PBMC), which were donated from thirteen patients with RCC and five healthy controls, were cultured with streptococcal preparation, OK432, and/or macrophage colony stimulating factor (M-CSF), and the TNF levels and IFN-gamma levels in the supernatant were evaluated. TNF activities were assayed by cytotoxicity to L929 cells and IFN-gamma activities were measured by inhibition of the cytopathic effects of sindbis virus on FL cells. The highest levels of TNF in the supernatant were 235.4 +/- 96.0 U/ml/1 x 10(4) cells in patients with renal cell carcinoma and 251.6 +/- 71.8 U/ml/1 x 10(4) cells in healthy controls, which were noted at 12 hours of incubation with the concentration of OK432 adjusted to 0.05 KE/ml. There was no statistically significant difference between the TNF activities induced by in vitro culture of PBMC obtained from patients with renal cell carcinoma and those from healthy controls. The production of TNF by in vitro culture of PBMC with OK432 of 0.05 KE/ml was augmented by adding 100 U/ml M-CSF especially at 48 and 72 hours of incubation, whereas M-CSF alone did not stimulated TNF production. The medium levels of IFN-gamma in six different cultures of PBMC with 0.05 KE/ml OK432 at 12, 24 and 48 hours of incubation were 1.15 +/- 0.34 U/ml/l x 10(4) cells, 2.23 +/- 0.93 U/ml/l x 10(4) cells, and 7.83 +/- 4.00 U/ml/l x 10(4) cells, respectively.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1507729 TI - [Clinical analysis of multiple primary cancers associated with bladder cancer]. AB - Among 321 bladder cancer cases from 1975 to 1989, 43 cases (13.4%) were found to have multiple primary cancers (MPC) and 278 cases without MPC (86.6%). These two groups were compared with regard to their clinical and pathological features. Mean age of patients when the bladder cancer was diagnosed was 68.9 +/- 8.9 in MPC cases and 65.7 +/- 12.3 (mean +/- S.D.) in cases without MPC. The male to female ratio was 3.8 to 1 and 2.6 to 1, respectively. The common sites of MPC were the lung, stomach and rectum, all of them being the organs often involved with cancer. Prostatic cancers in eight of 12 MPC cases were incidentally found in total cystectomy specimens. The sites of the synchronous and metachronous MPC involving lung, stomach and rectum cancers showed relatively even distribution. In males, the most common synchronous MPC included prostatic cancer, but in females, the diagnosis of uterine cancer tended to be made prior to the diagnosis of bladder cancer. In two cases, there was a strong suspicion that the therapy for the first cancer contributed to the occurrence of the second cancer. In the present study, no significant differences were noted with regard to clinicopathological characteristics of bladder cancer between the group with MPC and that without MPC. The five years survival rates from the beginning of bladder cancer treatment were 48.8% and 64.9%, respectively, indicating that the prognosis of the MPC cases was significantly worse (p less than 0.05) than that of cases without MPC. The most common cause of death in MPC cases was due to cancers other than bladder (36%).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1507730 TI - [Study of factors requiring more than two ESWL treatments]. AB - Nine hundred and fifty cases with renal and ureteral stones were treated by extracorporeal shock wave lithotripsy (ESWL) with Siements Lithostar unit from September, 1988 to October, 1990 at Kinki University Hospital. ESWL treatments were performed twice or more on 110 cases (DIFFICULTY GROUP). Ninety-seven cases who were cured by only one ESWL treatment were selected randomly as the control group. The two groups were retrospectively compared to study the factors requiring more than two times of ESWL treatments. There was a significant difference in the time of spontaneous stone discharge before ESWL treatment, the degree of hydronephrosis and the incidence of staghorn calculi as well as middle lower ureteral calculi between the two groups. There was not a significant difference but a tendency to a longer period of stone existing at the same position and a higher percentage of past history of percutaneous nephrolithotropsy (PNL) in DIFFICULTY GROUP. Because ESWL monotherapy is considered to have limitations, auxiliary procedures or other treatments such as PNL and transurethral lithotripsy are recommended for patients in who in the stones were poorly disintegrated by the first ESWL treatment. PMID- 1507731 TI - [Utricular papillomatosis. A case report]. AB - A case of utricular papillomatosis is reported herein. A 50-year-old male patient consulted our hospital with a complaint of asymptomatic macrohematuria. Endoscopic examination revealed papillomatous tumor tightly growing within the utricle. Transurethral resection of the tumor was performed. Histopathologically, the tumor consisted of numerous villous structures with slender fibrovascular cores and overlying cuboidal cells in 2 to 3 cell layers. Invasive growth or cellular atypia could not be found. Utricular papillomatosis is rare, and only one similar case was reported to my knowledge in the English literature for the last five years. Such rarity and peculiar clinicopathological characteristics prompted us to report this case. PMID- 1507732 TI - [A case of penile necrosis in a patient with diabetes mellitus]. AB - The patient was a 63-year-old male who was with having diabetes mellitus since 1967. Hemodialysis was carried out from June 1983 for diabetic nephropathy. Neuropathy and retinopathy were already present at that time. He complained pain in penile glans from the middle of June 1990. Three month later, partial penectomy was performed because of the development of black-mummy-shaped necrosis on the whole glans. Histopathological examination widely revealed luminal obstruction and formation of thrombus due mainly to vascular lesions as a result of diabetes mellitus. As far as we know, case reports of diabetes mellitus complicated with penile necrosis are extremely rare, and this present case seems to be the 2nd one in Japan and the 5th one in the world, including those reported previously in the West. PMID- 1507733 TI - Our benefactors. PMID- 1507734 TI - Testimonial immunity. PMID- 1507735 TI - UKSM-W is training physicians for underserved areas. PMID- 1507736 TI - Use of generic software programs in management of patient records and clinical research. AB - As personal computers become more cost-effective and user-friendly, they are bound to play an increasing role in the practice of medicine. This article is a description of how a commercially available database system adapted for medical record keeping has greatly facilitated the storage and retrieval of information. The designation of a data file for storage of patient records through the use of the systems menus, data entry, and conduct of searches for particular bits of data are described. Unique features such as custom-tailored computer reminders and project-specific programming are recommended as ways to improve the effectiveness of patient care and clinical research. When a single database system is used, the cost in terms of time, money and expertise is dramatically decreased, allowing the physician to optimize all aspects of the practice of medicine of exploiting computer technology with minimal to no knowledge of computer languages and/or programming. PMID- 1507737 TI - Rabies in Kansas, 1992. PMID- 1507738 TI - What is the practical value of digitalis in CHF? PMID- 1507739 TI - [Analysis of surgical treatment of 220 patients with acquired left aortic valve defect]. AB - The results of surgical treatment of 220 patients with acquired aortic valve malformations using two different methods were evaluated 5 years postoperatively. In 130 patients the aortic valve was replaced with "fresh" allograft and in the remaining 90 with prosthetic valve. In the group with allograft compared to patients after prosthetic valve implantation we have found: lower early mortality of 3% (p less than or equal to 0.01) (vs. 15.5%) higher probability of 5 years survival of 91.5% (p less than or equal to 0.001) (vs. 74.6%) low incidence of thromboembolic events of 1.7% (p less than or equal to 0.05) (vs. 8.8%) Allografts appear to be especially advisable and well tolerated in patients with active endocarditis. No statistically significant difference was found between both groups in relation to: probability of late death (5 years postoperatively), frequency of bacterial endocarditis during the postoperative course, frequency of valve failure. Slow increase of degenerative alterations during the succeeding postoperative years was distinctive for allografts, and the dysfunction of the implants appeared from the third postoperative year with the risk of 1.5% to 0.8% annually. Dysfunction of the prosthetic valve (perivalvular leak, thrombosis) was observed with the frequency of 5% to 1.3% annually. It developed quickly and usually was the cause of an urgent operation. The study demonstrates the advantages of allografts and their superiority over the prosthetic valves. Allograft implantation produces better life comfort for patients and diminishes or excludes the risk of thromboembolic complications. PMID- 1507740 TI - [Allogeneic heart valve--if it is a better choice, why is it used so rarely?]. PMID- 1507741 TI - [Platelet activation in young men after myocardial infarction: its relation to metabolic coronary risk factors]. AB - Selected parameters of platelet function as well as their relationship with metabolic coronary risk factors are studied in a group of 40 young survivors (aged 30-40 years) of myocardial infarction, now presenting stable coronary disease. Nineteen healthy men, of approximately similar age-span, constituted the control group. The following parameters were determined: platelet survival half time (via non-isotope method), intraplatelet activity of cyclooxygenase and lipoxygenase pathway of arachidonic acid (by measurements of malondialdehyde concentration before and after incubation with acetylsalicylic acid acid) and 125 I-fibrinogen binding to platelets. Moreover, the plasmatic concentration of total cholesterol, HDL-cholesterol, triglycerides, phospholipids, Apo A and B, total beta lipoproteins, glucose, uric acid as well as percentages of beta, prebeta, alpha lipoproteins and glycosylated hemoglobin were also studied. Platelet survival half-time in patients was significantly shortened (3.64 +/- 1.37 days) when compared with the control group (4.97 +/- 1.7 days). A higher intraplatelet activity of lipoxygenase pathway (2.02 +/- 0.62 and 1.49 +/- 0.54 nmol MDA/10(9) platelets, respectively) was also found. However, activity of cyclooxygenase pathway of arachidonic acid and 125-I-fibrinogen binding to platelets remained unchanged. Shortened platelet survival half-time and the hyperactivity of intraplatelet lipoxygenase pathway correlated with a reduced plasmatic concentration of HDL-cholesterol (r = 0.323, p less than 0.05 and r = -0.451, p less than 0.05, respectively). The remaining parameters of platelet function were not statistically related to metabolic risk factors. The values of platelet function indicators in subgroups of patients divided according to family history of coronary heart disease, oral glucose load test result, and submaximal exercise test result did not differ significantly.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1507742 TI - [Blood platelet activity after myocardial infarction]. PMID- 1507743 TI - [Transesophageal echocardiography for evaluation of the left coronary artery]. AB - The aim of the study was to evaluate the clinical usefulness of transesophageal echocardiography in the imaging of the left main coronary artery. The group tested--consisted of 26 patients with angina pectoris and 8 controls. The identification and adequate images of the left main coronary artery were obtained in 33 of 34 (97%) patients. In 5 of 26 patients with angina pectoris we observed stenosis of the left main coronary artery. The diameter stenosis of the lesion was judged to be greater than 50%. In addition, we tried to asses Doppler-derived parameters of blood flow. We have demonstrated that the pulsed Doppler study of the left main coronary artery is feasible. Comparison of patients with angina pectoris with the control group showed lower systolic flow velocities (35 +/- 10 cm/s vs. 55 +/- 15 cm/s) and slightly higher diastolic flow velocities (75 +/- 20 cm/s vs. 70 +/- 10 cm/s). This transesophageal examination holds promise for detecting pathologic vascular status. Although the sensitivity and specificity of this findings cannot be determined by our study, we believe that transesophageal echocardiography can provide a reference for the evaluation of patients with known or suspected ischemic heart disease. Further studies including larger groups of patients are recommended. PMID- 1507744 TI - [Indications for transesophageal echocardiography]. PMID- 1507745 TI - [Myocardial infarction without the Q wave]. PMID- 1507746 TI - [Heart rupture]. PMID- 1507747 TI - [Do antioxidant vitamins protect from arteriosclerosis?]. PMID- 1507748 TI - [Early rehabilitation of patients after uncomplicated myocardial infarction (study based on various publications of the last decade)]. PMID- 1507749 TI - [Sulfhydryl group levels and the succinate dehydrogenase activity in peripheral blood lymphocytes in patients with cancer of the stomach]. AB - In patients with gastric cancer, decrease in the level of SH-groups and activity of succinate dehydrogenase (SDH) of the peripheric blood lymphocytes which is indicative of the disturbance in oxidation-reduction processes was revealed. Degree of decrease in the indices depended on stage of the disease and severity of the course of a pathological process. SDH lymphocytic activity is the more sensitive test than content of SH-groups. The indices mentioned are used as an informative test for evaluation of the effectiveness of treatment. PMID- 1507750 TI - [Use of laser irradiation in the treatment of lung tumors]. AB - Endobronchial laser therapy was employed in the complex of treatment of 90 patients with tumorous pulmonary diseases. An LG-75 helium-neon laser with the output power of 20 mW was used. A pronounced therapeutic effect was noted in 75 patients. Preoperative recanalization of the bronchi was performed in 25 patients. The YAG-laser based plant "Raduga-1" was used as a source of radiation. No complications after the operation were noted. An antineoplastic effect of the high-energy laser radiation was noted. PMID- 1507751 TI - [Rare combined interventions in primary postoperative cancer of the stomach]. PMID- 1507752 TI - [Radical surgical treatment of patients with cancer of the stomach]. AB - The results of surgical treatment of 158 patients with gastric cancer, using the original techniques for the esophago-gastric and esophago-intestinal anastomoses formation, have been summarized. Gastrectomy was performed in 65.2%, subtotal proximal reaction of the stomach--in 8.9%, subtotal distal resection--in 25.9% of the patients. The postoperative lethality was 3.2%. At late complex examination, I stage reflux esophagitis after gastrectomy was observed in 3 (3.4%) patients, after proximal gastric resection--in 1 (8.3%). After the operation, 32 (20.3%) patients are alive for 5 and more years. PMID- 1507753 TI - [Diagnosis of gastric cancer and the quality of the examination of non hospitalized patients in the polyclinic of an oncological hospital]. AB - The methods for diagnosis of gastric cancer in 711 patients who were not hospitalized because of age and tumor dissemination have been analysed. The roentgenologic, endoscopic, morphologic and radionuclide methods of investigation in these patients were used less frequently than in patients treated in a hospital. The examination, being not thorough, didn't permit to establish the correct diagnosis and choose an adequate method for treatment. PMID- 1507754 TI - [Surgical tactics in the treatment of villous adenoma of the stomach and intestine]. AB - The results of endoscopic and surgical treatment of 183 patients with villous and tubular-villous adenoma of different location are presented. Adenoma of the stomach and duodenum are subject to malignization more often than colonic adenomas. Endoscopic polypectomy is a method of choice in treatment of benign adenoma with a diameter no more than 4 cm. Resection of the involved areas of the stomach and intestine is indicated in detection of a malignant mass and a large benign tumor causing considerable loss of fluid from the organism. PMID- 1507755 TI - [Study of immunologic reactivity of patients with cancer of the stomach based on the data of the adhesive capacity of lymphocytes]. AB - In patients with gastric cancer, the increase in adhesive lymphocytic capacity, as compared to a control, was revealed. It is indicative of the reduction in production of lymphokines, causing inhibition of adhesion. The highest value of the index was noted in IV stage gastric cancer. The results of study of the adhesive properties of the peripheric blood lymphocytes allow to judge about the state of cellular immunity, and in the complex with the other clinico-laboratory findings, are of a prognostic value. PMID- 1507756 TI - [Multiple primary malignant neoplasms of the large intestine]. AB - Of the 3182 patients with malignant tumors of the large intestine, in 140 (4.4%), the primary multiple malignant neoplasms were revealed: in 59 (42.1%) of them- the synchronous, in 81 (57.9%)--the metachronous ones. Surgical treatment was performed in 137 (97.9%) patients, including the radical treatment--115 (83.9%). The postoperative lethality was 7.3%. 75.3% of the patients are alive for five years, 21.3%--for ten years. PMID- 1507757 TI - [Combined treatment of recurrent lung cancer]. AB - The combined treatment of 36 patients for a pulmonary cancer recurrence included the performance of preoperative radiotherapy, reoperation and postoperative polychemotherapy. After reoperation, 3 (8.3%) patients died. In 17 of the 28 patients, the treatment was ineffective, all of them died. The mean lifetime was 20.8 mos. Eleven patients are alive for from 2 to 50 mos with no tumor recurrences, or metastases revealed. PMID- 1507758 TI - [Measuring the depth of location of non-organic neoplasms in the small pelvis]. AB - The objective technique for determination of the depth of location of the lower and upper poles of a non-organic mass in the small pelvic cavity, irrespective of sex and age of a patient, has been developed. The correct determination of a mass location permits to choose an optimal surgical approach, increase the operability rate of the tumors and reduce the incidence of complications. PMID- 1507759 TI - [Expediency of preventive lymphadenectomy in patients with skin melanoma]. AB - On the basis of the results of treatment of 87 patients with skin melanoma, the expediency of lymphadenectomy performance irrespective of the fact whether the regional lymph nodes were, or were not palpated was substantiated. Performance of this operation permitted 3-fold reduction of lethality. PMID- 1507760 TI - [Late monitoring for predicting of the outcome of the treatment of gastric cancer]. AB - The results of late monitoring of 114 patients with III stage gastric cancer who survived 10 years and longer after the radical operation performance are presented. Forty patients who developed recurrence and generalization of tumorous process within the first 5 years after the operation entered the control group. All the patients died. The quantitative and qualitative prognostic factors were established. On the basis of the data of blood analysis, a reliable prognostic index has been developed. PMID- 1507761 TI - [Diagnosis of desmoid of rare location]. PMID- 1507762 TI - [Organization of early diagnosis of colorectal cancer]. PMID- 1507763 TI - [New methods of instrumental diagnosis of colorectal cancer]. PMID- 1507764 TI - [Clinical aspects and diagnosis of lymphogranulomatosis of the stomach and duodenum]. PMID- 1507765 TI - [Non-organic tumor in the pelvic cavity simulating perineal hernia]. PMID- 1507766 TI - [Cyst of the round ligament of the uterus simulating inguinal hernia]. PMID- 1507767 TI - [Primary melanoma associated with skin cancer]. PMID- 1507768 TI - [Multiple primary metachronous cancer of organs of the digestive tract]. PMID- 1507769 TI - [Favorable outcome of incompetence of sutures of the esophageal- small intestinal anastomosis in a patient after gastrectomy for cancer of the stomach]. PMID- 1507770 TI - [Correction of endogenous poisoning in patients with peritonitis in gastric and intestinal tumors]. AB - Peculiarities of endogenous intoxication in peritonitis in 63 patients with cancer of the stomach and intestine were studied. Three degrees of the intoxication syndrome severity were distinguished: the mild, moderate and severe ones. It is shown that the severity degree of intoxication depends on a phase of peritonitis, stage of tumorous process and state of anti-infective protection of an organism. The steps for surgical detoxication of an organism, depending on severity degree of endogenous intoxication, were defined. Use of a complex of treatment permitted to reduce postoperative lethality of the patients to 33%. PMID- 1507771 TI - [Early diagnosis of gastric cancer and use of pylorus-sparing gastrectomy]. PMID- 1507772 TI - [A case of successful conservative treatment of recurrent cancer of the stomach]. PMID- 1507773 TI - [Squamous cell carcinoma of the lung associated with chondromatous hamartoma]. PMID- 1507775 TI - [Synchronous development of carcinosarcoma of the uterine body and secondary cancer of the ovary]. PMID- 1507774 TI - [Multiple surgical interventions in granulosa cell cancer of the right ovary]. PMID- 1507776 TI - [Goblet cell carcinoid of the appendix]. PMID- 1507777 TI - [A case of pseudoepitheliomatosis in a localized form of primary skin melanoma]. PMID- 1507778 TI - [Generalized cysticercosis associated with breast cancer]. PMID- 1507779 TI - [Metastasis of rectal cancer to the quadriceps muscle of the thigh]. PMID- 1507780 TI - [Nephrectomy with hemicolectomy and resection of the ileal segment in cancer of the right kidney]. PMID- 1507781 TI - [Giant lipoma of the retroperitoneal space]. PMID- 1507782 TI - [A case of carcinosarcoma of the liver]. PMID- 1507783 TI - [Successful treatment of Gardner syndrome]. PMID- 1507784 TI - [Inflammatory pseudotumors of the abdominal organs]. PMID- 1507785 TI - ["No-stitch" cataract surgery as a routine procedure. Technique and experiences]. AB - We present a modified self-sealing wound construction with a trapezoidal incision for No-Stitch-Technique. Due to the form of the incision and the elasticity of the sclera the 6 mm incision can be extended to about 8 mm which allows an implantation of conventional PMMA-IOL without excessive scleral stretching. Since the beginning of 1991 this technique has been used routinely in our clinic with over 1500 operations. The No-Stitch-Technique has, in comparison to the sutured corneo scleral incision, two main advantages: the wound closure has a five fold higher stability and an induced astigmatism of less than 1.0 dpt. Other postoperative complications, such as wound dehiscence, iris prolapse and hypotony syndrome, were significantly eliminated. PMID- 1507786 TI - [Effect of intraocular administration of acetylcholine and carbachol on postoperative intraocular pressure after cataract surgery]. AB - In a consecutive series of 90 patients we examined the effect of intracameral acetylcholine and carbachol on intraocular pressure following extracapsular cataract surgery. In all cases phacoemulsification and implantation of a folded polyhema intraocular lens under healon was performed. After evacuation of the viscoelastic substance from the capsular bag behind the inserted lens and wound suturing we instilled 0.5 ml 1% acetylcholine, 0.5 ml 0.01% carbachol or 0.5 ml balanced salt solution respectively into the anterior chamber. Without the influence of antiglaucomatous drugs applanation tonometry was performed 6 and 18 hours postoperatively. When compared with preoperative values intraocular pressure decreased in the carbachol group (-2.8 mm Hg) but increased in the acetylcholine group (+0.6 mm Hg) and control group (+4.7 mm Hg). 18 hours postoperatively the mean change was -3.0 mm Hg in the carbachol group, +0.8 mm Hg in the acetylcholine group and +2.3 mm Hg in the control group. Intraocular pressure exceeding 22 mm Hg at 6 hours was observed in 33% of the control group and 13% of the acetylcholine group but none of the carbachol group. At 18 hours intraocular pressure was still elevated in 13% of the control group, 10% of the acetylcholine group and 3% of the carbachol group. Reviewing our results we conclude that the evacuation of viscoelastic substances from the capsular bag behind the implanted lens reduces the incidence of pressure rises in the early postoperative period. This effect can be enhanced by the use of acetylcholine and, the more potent, carbachol. PMID- 1507787 TI - [Complications of laser keratomileusis with the excimer laser (193 nm)]. AB - Complications of photorefractive keratectomy (PRK) for myopia correction are presented based on 615 procedures with a follow-up of up to 2 years. Intraoperative complications with experienced surgeons are extremely rare. The used laser system worked without technical failures for the last 18 months. Gross eccentricities of the ablative zone (1.0 mm to 1.5 mm) occurred in two eyes (0.3%). Also, epithelial disorders are very rare. Recurrent erosions did not occur. Increased intraocular pressure due to the postoperative steroid medication (dexamethasone 0.1% or prednisolone 1%) was manifest in about 30% in patients with a baseline myopia of up to -9.0 D. In myopia over -9.0 D the incidence of steroid glaucoma was about 50%. Steroid responders reveal an increased risk of overcorrection. Subepithelial haze is a common symptom after PRK. Scarring interfering with vision correlates with the amount of attempted correction: up to 6.0 D the incidence of scars is about 0.5% and increases to more than 10% in corrections of more than 10 D. Also, undercorrections of more than 1 D depend strongly on the attempted correction. The most severe complication was a noninfectious corneal ulcer in a patient with systemic lupus erythematosus. Therefore, autoimmune and connective-tissue diseases represent an absolute contraindication for PRK. Corrections of more than 6.0 to 7.0 D should be considered as a relative contraindication for PRK at this time. PMID- 1507788 TI - [Retinal circulation and current blood glucose value in diabetic retinopathy]. AB - In 42 type II diabetic patients with nonproliferative diabetic retinopathy the arm-retina time (ART) and arteriovenous passage time (AVP) were measured by means of videofluorescein angiography. Glycosylated hemoglobin (HbAlc) as a parameter of longterm diabetic control and the blood glucose level were determined. The ART in the diabetics was similar to the ART of normals and the AVP was significantly prolonged. HbAlc level ranged between 5.6 and 12.2% (8.6 +/- 1.7%) and the blood glucose level between 4.5 and 22.9 mmol/l (11.4 +/- 4.5 mmol/l). Significant correlations were found between AVP and blood glucose (r = 0.37) and between AVP and HbAlc (r = 0.49). No correlation was found neither between ART and blood glucose nor between ART and HbAlc. A multiple stepwise regression analysis shows that of both investigated parameters HbAlc is the predicting variable for AVP. These results show that in diabetic patients the retinal blood flow is more influenced by the longterm diabetic control than by the blood glucose level at the time of examination. PMID- 1507790 TI - [Study of blood flow velocity in the central retinal artery using pulsed Doppler sonography]. AB - Using the method of pulsed-wave ultrasound-Doppler-Sonography (2 MHz-probe; sample volume 10 mm; variable invading depth by using a so-called "flow-pipe"; transmission range 10 mW/m2), the author demonstrates an objective, reproducible and exact clinical test to examine blood-circulation in central retinal artery. Because of the fact, that the angle of ultrasound is nearly zero-degrees to central retinal artery, accuracy of measurement flow velocity is nearly hundred percent. Method can be applied without problems by using intracranial Doppler Sonography (ICD). It is less expensive than Duplex-Sonographie for instance. PMID- 1507789 TI - [A new surgical procedure in angle block glaucoma]. AB - Authors show the results obtained in 29 eyes of 29 patients with closed angle glaucoma operated with ECCE plus posterior chamber IOL implantation. After a follow up varying from 1 to 35 months (mean = 20.7) all eyes are under good control (25 without therapy, 4 with topical therapy) of I.O.P. Authors report on the "rationale" of their surgical approach: particular anatomo-functional features of the eyes affected by closed angle glaucoma. Pre-op. and post-op. biometrical and gonioscopical findings are described and discussed. PMID- 1507791 TI - [Orbital, osseous, meningeal and cerebral findings in oculodermal melanocytosis (nevus of Ota). Clinico-histopathologic correlation in 2 patients]. AB - In two patients suffering from congenital oculodermal melanocytosis (nevus of Ota) orbital, osseous, meningeal, and cerebral manifestations are documented. In a 38-year-old European with a nevus of Ota on the right side an ipsilateral orbital tumor was diagnosed and surgically removed. The histological examination revealed a primary spindle shaped malignant melanoma of the orbit. In addition, many benign melanocytes were found in the optic nerve, in the extraocular muscles, in the orbital fat tissue, and in the dura of the sphenoid. In a 17-year old Ethiopian with a nevus of Ota of the right side an increase in size of the pigmented process was observed during puberty in the orbital fat tissue, in the extraocular muscles, in the optic nerve, in the periorbital bones, in the temporal muscle, and in the cortex of the frontal brain lobe. A deep excision from the lower eye lid revealed a histologically benign oculo-orbito-dermal melanocytosis. An irradiation was performed because of growth again after segmental excision, however without success. In the ipsilateral eye a secondary open-angle glaucoma was diagnosed. In the nevus of Ota an involvement of the orbit and of the meningo-cerebral tissue must be considered. PMID- 1507792 TI - [Bilateral colobomatous microphthalmus with orbital giant cysts in incomplete tetrasomy 22]. AB - A case of bilateral microphthalmos with orbital cysts is presented with clinical, echographic, CT and genetical findings. An incomplete trisomy 22 is shown as the likewise cause of the malformation. No further symptoms known to be part of the cat-eye-syndrome could be detected. PMID- 1507793 TI - [Results of animal experiment study of a new enucleation filling of bio vitroceramics--Bioverit I and II (bioactive and biocompatible)]. AB - The results with two new enucleation prothesis made of Bioverit are presented. After unilateral enucleation 14 rabbits received bioreactive, 14 rabbits biocompatible and 9 rabbits nylon prostheses. Implantation periods: 1-13 months. The tissue surrounding of the prostheses was studied histologically, the ceramic electron microscopically. Of 28 ceramic prostheses, 26 were adapted very well. Bioverit ist excellently suited as orbital prosthetic material, even half-open implants are possible. PMID- 1507795 TI - [Annual meeting of the Bavarian Ophthalmologists Association. Wurzburg 28-29 June 1991. Abstracts]. PMID- 1507796 TI - [G. F. Kosmetatos. His work and his life]. PMID- 1507794 TI - [Reproducibility of the results of two non-contact tonometers. Comparison with the Goldmann applanation tonometer]. AB - Two non-contact tonometers (Keeler "Pulsair" and Reichert NCT II) were compared regarding the reproducibility of their readings mutually and with referring literature about Goldmann applanation tonometry. Differences of maximum 2 mmHg were found using Pulsair tonometer/NCT II in 61%/83% for two subsequent readings, in 73%/89% for subsequent mean values of 3, in 86%/95% for subsequent mean values of 6 and in 97% each for subsequent mean values of 9 readings. The confidence intervals of 90% were +/- 5.87 mmHg/+/- 3.38 mmHg for subsequent readings, +/- 3.75 mmHg/+/- 2.29 mmHg for mean values of 3, +/- 2.63 mmHg/+/- 2.00 mmHg for mean values of 6 and +/- 2.13 mmHg/+/- 1.61 mmHg for mean values of 9 readings, signifying the high scatter of Pulsair measurements; reaching the NCT II's reproducibility, which is comparable to that of the Goldmann readings of an experienced observer, requires mean values of a higher number of Pulsair readings. The discreet pressure lowering effect occurring with repeated NCT II applications could not be observed during Pulsair measurements. Perhaps the Pulsair instrument might be interesting for scientific questions, but it is not recommendable for routine diagnostic. PMID- 1507797 TI - [Comment on disinfection of tonometer probe by Dr. Heine with a request to contact Prof. Dr. Daschner]. PMID- 1507799 TI - [Acute drug-induced hepatitis in a patient with peptic ulcer]. PMID- 1507798 TI - [A case of polycystic liver and kidney complicated by uremia and myocardial necrosis]. PMID- 1507800 TI - [Giant leiomyoma of the proximal part of the stomach]. PMID- 1507801 TI - [Difficult diagnosis in a case of Caroli's disease]. PMID- 1507802 TI - [Principles of the rehabilitation of patients with bronchopulmonary diseases]. PMID- 1507803 TI - [DIC syndrome: current views and problems]. PMID- 1507804 TI - [Methodological features of doctoring]. PMID- 1507805 TI - [Public health and medical departments of the universities in Russia at the beginning of the 19th century]. PMID- 1507806 TI - [Several errors in the recording of S. P. Botkin's life and activities]. PMID- 1507807 TI - [History of aspirin research]. PMID- 1507808 TI - [The Kiev school of therapists (the 150th anniversary of the Kiev Medical Institute)]. PMID- 1507809 TI - [Lesions of the lungs in hemoblastoses]. PMID- 1507810 TI - [Systemic effects of smoking (review of foreign literature)]. PMID- 1507811 TI - [Lesions of the cardiovascular system in acquired immunodeficiency syndrome]. PMID- 1507812 TI - [Laser therapy of peptic ulcer]. PMID- 1507813 TI - [Current problems of clinical radiation medicine]. AB - Results, prospects of studying the effects of ionizing radiation on human beings are considered with regard to the outcomes of the Chernobyl catastrophe and the results of a 5-year implementation of the All-Union Programme C-27. Present-day problems and approaches to investigation for the nearest 5-year period are formulated. PMID- 1507814 TI - [Fibrinolysis, interleukins and coronary atherosclerosis]. AB - The study of the fibrinolytic system and the activity of interleukin 1 and 2 in 75 patients with various cardial manifestations of atherosclerosis (angina of effort, angina decubitus, arrhythmia, symptomatic hypertension) revealed a decrease in the activity of plasminogen--a blood activator--in patients with angina of effort, angina decubitus and cardiac arrhythmias. In those with atherosclerotic hypertension the activatory activity was in the normal limits. A decrease in the activity of interleukin 1 and 2 was noted in all those examined. PMID- 1507815 TI - [State of hemostasis during naphthalane treatment of patients with obliterating atherosclerosis of the vessels of the lower limbs]. AB - A total of 67 patients with obliterating atherosclerosis of the vessels of low extremities were followed up in the treatment at the Naphthalane health resort. The patients with the disease stages I, IIA and IIB were subjected to sitting and general naphthalane bath therapy. The studied patients were investigated for the values of the blood coagulation and functional abilities of thrombocytes before and after naphthalane treatment. Analysis of the results obtained demonstrated a favourable effect of naphthalane on hemostasis displaying hypocoagulative effect and improving the blood viscosity. The use of naphthalane as a multiprofile factor in the treatment of the aforementioned patients was found to be advisable and could be considered as a pathogenetic method of treatment for those suffering from this disease. PMID- 1507817 TI - [Possible use of glucocorticoids in the diagnosis of lung lesions and anemia in autoimmune diseases]. AB - The author described a new pattern of the diagnosis of autoimmune processes in the lungs based on the results of a short-term pharmacological load with glucocorticoids (prednisolone, 30 mg per day for 7-10 days) and the successive evaluation of the X-ray picture time-course in the lungs in the frontal roentgenographic view before and after the load. He accounted for the alteration in the number and size of infiltrations and foci as well as the contents of the fluid in the pleura and interlobular fissures. The usage of the load proposed made it possible to reduce the terms and increase the preciseness of the diagnosis of pulmonary autoimmune conditions and to define the practicability of prolongation of the glucocorticoid treatment. Glucocorticoid load technique originated with the author permitted one to establish the autoimmune nature of anemia with regard to its tendency towards the regression and thus to define the policy of its further treatment as well as to differentiate autoimmune anemia in rheumatic patients from the anemia in the patients with paraneoplastic rheumatic syndromes. PMID- 1507816 TI - [Prospective course of therapy arresting attacks of atrial fibrillation in patients with preexcitation syndromes]. AB - A comparative study of antiarrhythmic drugs was performed in 81 patients with atrial fibrillation attacks in the presence of preexcitation syndrome. The first intravenous administration of cordarone was effective in 84.06%, disopyramide--in 69%, ajmaline in 44.8, verapamil in 42.1, novocaine amide in 39.4 and ethacizin in 38.5% of the patients. The first oral administration of quinidine and kinilentin arrested 80.4% of arrhythmia attacks, disopyramide 66.7% propranolol and mexitil 37.5 and 33.3%, respectively. Prospective evolution of antiarrhythmic therapy manifested with decreased therapeutic efficacy of the drugs from 55.7 to 26.2% in the whole group during the period of 1-5 years. PMID- 1507818 TI - [Antiphospholipid syndrome and resistance to replacement therapy in hemophilia]. AB - The paper described the appearance of lipoid anticoagulant (LA) in the presence of hepatitis B virus in the blood of hemophilia A patient. Profuse and long-term bleeding after the extraction of the tooth that failed to be treated with big doses of cryoprecipitation was noted. Intense replacement therapy resulted in the appearance of factor VIII inhibitor in a titre of 4.5 units per ml in the patient's blood. Big-dose prednisolone therapy helped an immediate arrest of the bleeding and a rapid decrease in LA titration. The levels of factor VIII inhibitor preserved in the same values. The study exhibited the ability of LA to impede the arrest of the bleeding and the response to the replacement treatment in hemophilic patients. PMID- 1507819 TI - [Megakaryocytopoiesis in patients with acute infectious destruction of the lungs]. AB - Partial megakaryocytograms were studied in patients with acute infectious destructions of the lungs. Acid phosphatase and glycogen megakaryocytic levels, overall number of megakaryocytes elucidated the role of the central link of the system megakaryocyte--platelet in the onset of thromboembolism and hemorrhagic complications arising in the above patients. Inefficiency of megakaryocytopoiesis in pulmonary and pleural acute pyo-destructions is under discussion. PMID- 1507820 TI - [Ultrasonography of the gallbladder in patients with hemoblastoses]. AB - A total of 402 patients with acute or chronic leukemia and chronic cholecystitis and 100 healthy controls were exposed to ultrasonic biliography. It was revealed that leukemic infiltration of the bladder wall, increased pressure in the portal system, hypoalbuminemia and the concurrent diseases of the bladder could be the main causes of the alterations in the size and form of the bladder and the width of its walls in hemoblastosis patients. It was stated as well that the thickening of the bladder wall was an obligatory diagnostic criterion for not only chronic cholecystitis but various patterns of hemoblastoses as well. The authors suggested that echolocation of the gall bladder should be done in combination with clinical and morphological verification of the tumor process and its stages that undoubtedly would be of significant value in the choice of therapeutic policy. PMID- 1507821 TI - [Intensive plasmapheresis: complications and their prevention]. AB - Upon the analysis of 246 plasmapheresis sessions performed for autoplasma provision, the correction of the blood rheology and the decrease in endogenic intoxication of 216 patients, it was stated that the frequency of various reactivity and complications comprised 12.9%. The causes of these complications and the means of their prevention were analyzed. PMID- 1507822 TI - [Comparative assessment of various programs of plasmapheresis in the combined treatment of patients with rheumatoid arthritis]. AB - Therapeutic efficacy of various plasmapheresis (PA) programmes was comparatively studied in 92 patients with rheumatoid arthritis. PA performed as a placebo (the control group) confirmed the efficacy of PA in the patients with rheumatoid arthritis. The choice of a particular regimen of the procedure depended on the health status of the patient. The programme of PA with the elimination of one volume of the circulating plasma (VCP) turned to be the most effective in the patients with highly active course of the disease while the procedures with the elimination of 1/2 and 1/4 VCP should be used in those with moderate or minimal activity of the disease. The assessment of the therapeutic response should be based on the clinical data, ESR and the contents of circulating immune complexes- the most dynamic laboratory tests. PMID- 1507823 TI - [Effects of hemosorption on the regulation of calcium metabolism in patients with rheumatoid arthritis]. AB - A clinical response to hemosorption and the alterations in the calcium regulatory systems associated with the treatment mentioned were studied in 42 patients with rheumatoid arthritis. The use of hemosorption in the multiple modality treatment resulted in a manifest clinical and laboratory positive effect featured by the improvement of the general condition of the patient, a decrease in the values of the joint syndrome and the activity of the inflammatory processes as it was evidenced by routine laboratory tests and the time-course of the contents of beta 2-microglobulin in the blood and synovial fluid. Hemosorption helped the correction of the performance of the systems of calcium regulation: a decrease in parathyrin contents, an increase in the contents of calcidiol, osteocalcin, and ionized calcium. PMID- 1507824 TI - [Clinical effectiveness of plasmapheresis and lymphocytoplasmapheresis in patients with systemic scleroderma]. AB - Clinical effect of plasma- and lymphoplasmapheresis in patients with various patterns of sclerodermia systematica was studied in 12 females with subacute and chronic course of the disease. The failure of the drug therapy preceded, the complications associated with corticosteroid treatment performed were the indications to the aforementioned procedures. The treatment course comprised 3-5 procedures with an interval of 2-3 days. During 1 plasmapheresis session 1000 1200 ml of the plasma were removed and 1100-1250 ml of the plasma and 4.5.10(9) 7.0.10(9) lymphocytes were removed by a session of lymphoplasmapheresis. The results obtained evidenced a positive influence of plasma- and lymphoplasmapheresis on the course of sclerodermia systematica, contributed to a decrease in the clinical manifestation of the disease and laboratory data indicating the activity of inflammation, led to a more rapid regression of the main symptoms of the disease than it was recorded during the routine treatment, promoted a longer remission and a significant reduction of the hormone dosage. PMID- 1507825 TI - [Amyloidosis in systemic lupus erythematosus]. AB - Based on the authors' experience from 1982 to 1990 it was noted that out of 26 cases of renal amyloidosis in the presence of nonpurulent and purulent conditions 2 patients (7%) demonstrated the association with systemic lupus erythematosus (SLE). It was also noted that amyloidosis developed in the patients with a long history of the disease. Long-course immunosuppression treatment could be regarded as the other factor-of-risk for amyloidosis development. Histochemical examination of both patients demonstrated that amyloid deposits in the renal glomeruli were resistant to the potassium permanganate effect and consisted of AL protein. The results obtained indicated the possibility of appearance of immunoglobulins AL--the proteins of the primary amyloidosis--synthesized in the spectrum in the SLE presence as well as their deposition in the renal glomeruli. As a possible cause of proteinuria and the nephrotic syndrome in SLE patients amyloidosis should be diagnosed in the life time and be regarded in the choice of therapeutic policy as well as in the assessment of pulse immunosuppressive therapy practicability. PMID- 1507826 TI - [Cardiolipin antibodies in acute rheumatic fever]. AB - The paper presented the results obtained in studying the patients with acute rheumatic fever for antibodies to cardiolipin (ACL). The study resulted in the establishment that the development of immunopathies in the presence of acute rheumatic fever combined with the acute streptococcal infection was accompanied by hyperproduction of ACL (more common IgG versus IgM isotypes). The phenomenon mentioned widened the spectrum of acute infectious diseases associated with an increase in ACL synthesis. It was also stated that increased ACL contents were closely related with the involvement of the cardiac valves. Authentic clinical and echocardiological signs of the heart disease were mainly revealed in the patients with high contents of IgG and IgM isotypes of ACL. A certain relationship between the laboratory activity of the disease and ACL hyperproduction was noted as well. The latter permitted the discussion on the impact of streptococcal infection initiating the development of acute inflammation on the hyperproduction of ACL. PMID- 1507827 TI - [Human campylobacteriosis caused by Campylobacter fetus]. PMID- 1507828 TI - [Blood lymphocytes and their cytochemical activity in patients with peptic ulcer during different seasons]. PMID- 1507829 TI - [Lipid peroxidation in the blood and tissues of patients with peptic ulcer]. AB - Investigation of 67 patients with peptic ulcer revealed a reliable activation of lipid peroxidation processes both in the blood of the patients and in the mucous membrane in the area of the ulcer location immediately. The activation of lipid peroxidation resulted in a decrease in the contents of phospholipids in the biological membranes of the mucosa cells. The alterations revealed occurred in the presence of inhibition of the antioxidant system of the body. The authors proved the efficacy of the use of antioxidant formulations and ultraviolet irradiation of the blood in the treatment of patients which resulted in acceleration of the ulcer cicatrization and the reduction of the inpatient period as well as the improvement of surgical results. PMID- 1507830 TI - [Evaluation of the effectiveness of laser and drug therapy of patients with duodenal ulcer]. AB - The paper presents clinical and morphological assessment of therapeutic response in 97 patients aged from 20 to 65 years with the diagnosis of duodenal ulcer from 1 to 15 years. Routine treatment was performed in 32 and drug therapy in combination with local He-Neon radiation of the ulcer was performed in 65 patients. Higher therapeutic response especially in those with the disease duration not longer than 5 years was revealed in case of laser therapy versus the routine drug treatment. The effect of laser radiation either on the ulcer mucous coat or far from it resulted in a moderation of inflammatory and an increase of reparative processes. More rapid terms of ulcer healing is of a certain time saving effect. PMID- 1507831 TI - [Theory of universal functional blocks and fundamental biomedical problems]. AB - The paper presents the main aspects of the theory of elementary functional blocks. In accordance with the theory considered high specialization of the complex functions could be reached due to the recombination and transposition of a large though limited set of molecular machines realizing elementary biological operations. The authors proved that the theory of universal functional blocks became a fundamental aspect of the medical theory as it permitted one not only to explain and classify a certain part of clinical and clinicophysiological phenomenology but was of significant prognostic value. PMID- 1507832 TI - [Possibilities of prognostication of complications in duodenal ulcer]. AB - The authors investigated a prognostic value (with respect to the complications) of certain laboratory parameters used in the examination of the gastric juice in patients with duodenal ulcer (DU) as well as the prognostic value of certain anamnestic data. A total of 100 patients with DU who had been followed up for 5-6 years were under study. The results obtained demonstrated the most informative values for the DU-related complications turned to be the parameters of the performance of the defense mechanisms of the gastroduodenal area (the contents of mucous proteins, the coefficient of the gastric juice defense), the levels of gastric secretion and acidification (the quantity of the juice, the per hour discharge of hydrochloric acid) as well as the ratio between the coefficient of the defense and the coefficient of the pepsin aggression that reflected the ratio between the aggressive and defensive factors of the gastric juice. Defined discriminant functions permitted the prognostication of complications appearance correct within 80-90%. PMID- 1507834 TI - [Improvement of treatment results in patients with peptic ulcer]. AB - A total of 980 patients operated on for peptic ulcer of the stomach and duodenum were followed up. Out of them 784 (80%) patients had complications: 273 (27.9%)- perforations, 263 (26.8%)--bleedings, 165 (16.8%)--stenosis, 67 (6.8%)- penetration, 16 (1.6%)--malignant transformation of the ulcer, the rest of them, 19 (20%) patients, had chronic callous ulcers. Factors of risk for complications associated with peptic ulcer were indicated. Timely planned surgical intervention advancing the development of severe complications is found to be necessary for the improvement of the therapeutic response. PMID- 1507833 TI - [Duodenal ulcers that do not heal for a long time]. AB - The investigations of 43 duodenal ulcer cases in the patients whose ulcers failed to cicatrize after a 8-week treatment with almagel and vicalin or cimetidine monotherapy revealed the role of the hereditary load, smoking intensity, initial ulcer dimensions, the presence of antral erosions and a pronounced periulcerous duodenitis in the phenomenon of slow healing duodenal ulcer. There was no statistical difference between the values of the basal and pentagastrin stimulated levels of hydrochloric acid secretion in the morning, partial alkaline gastric secretion, gastrinemia, the rate of evacuation of the gastric contents into the duodenum, the outcome of pancreatic bicarbonates in the sample with exogenic secretin in those whose ulcers cicatrized after a 6-week therapy and those who failed to be cured after being exposed to the same therapy during 8 weeks. The production of hydrochloric acid in the evening and the incidence of manifest duodenal reflux were significantly higher in the patients with slowly healing ulcer. They also had a decreased sensitivity to the intraduodenal inflow of the hydrochloric acid that resulted in the increase of endogenic secretin (stimulating the production of pancreatic bicarbonates and their transport into the duodenum). In case the combination treatment with almagel and vicalin failed, the therapy with gastrocepin or sucralfate was employed. A supplementary course of sucralfate helped to reach a complete healing of noncomplicated ulcers even in the patients in whom the preceding cimetidine treatment failed. PMID- 1507835 TI - [Pathogenesis of anemia in abdominal typhus]. AB - Morphological parameters of the red cells were studied in 121 patients with typhoid-paratyphoid conditions. To obtain objective clinical data the authors studied the effect of LPS S. anatum on the intact red cells of healthy persons. The correlation of morphological disorders in the red cells of the patients and the controls revealed a significant role of intoxication in their origin. The research conducted revealed a relationship between the disorders in the erythrocyte membranes and the development of anemia in the patients. PMID- 1507836 TI - [Heparin in the treatment of patients with erysipelas]. PMID- 1507837 TI - [Differential diagnosis of dilated cardiomyopathy]. AB - Diagnostic criteria for dilated cardiomyopathy and those for its differential diagnosis with coronarogenic and non-coronarogenic (nonrheumatic myocarditis and other patterns of cardiomyopathy) as well as infiltrative myocardial lesions and some acquired and congenital heart diseases, pericarditis and cardiac tumors (myxomas) were presented. Emphasis was given to the analysis of the informative value of the current instrumental, mostly noninvasive, techniques. PMID- 1507838 TI - [Extracorporeal lithotripsy (review of the foreign literature)]. PMID- 1507839 TI - [Adult respiratory distress syndrome in patients with infection]. AB - A grave complication of sepsis is a respiratory distress in adult persons observed by the authors in 11.3% of the examinees. The syndrome of respiratory distress could develop in the presence of toxico-infectious (septic) shock or severe allergic immediate responses to the administration of certain drugs. The main approaches to the treatment of respiratory distress in adult septic patients turned to be glucocorticoids, heparin and recurrent sessions of hemosorption. PMID- 1507840 TI - [Use of the expired air condensate in the study of biochemistry of bronchial contents in patients with bronchial asthma]. AB - A total of 7 patients with premorbid adjustment (PA) and 13 patients with bronchial asthma (BA) were comparatively studied for the content of calcium, magnesium and biogenic amines (histamine, serotonin) which were assessed with atom absorption spectrophotometry and fluorimetry in the condensate of expired air (CEA), fluid of the bronchial wash-off (FBW) and bronchoalveolar lavage (BAL). It was revealed that the studied values in CEA were similar to those in FBW and BAL. The results obtained indicated that CEA adequately demonstrated the biochemical composition of bronchial contents in various generations and alveoli. CEA availability and high informative value permitted it to be employed in the research into the mechanisms of bronchial obstruction as well as in the control for the efficacy of BA and PA treatment. PMID- 1507841 TI - [Systolic and diastolic arterial blood pressure in patients with angina pectoris (a long-term study)]. AB - The prospective follow-up of 190 patients with angina pectoris (males, aged 40-59 years) which lasted for 26 years revealed that only 37 (19.5%) persons survived. Out of 153 patients who expired, 76% were subjected to pathoanatomical or medicolegal examination. It was revealed that cardiovascular lesions were responsible for 71.9% death cases in patients with angina pectoris. The elevation of both systolic and diastolic arterial pressure corresponds with a general tendency to the rise of lethality from ischemic cerebral or heart disease though the impact and character of their influence is different. PMID- 1507842 TI - [Clinical effectiveness and potential hazards of combined kordaron and quinidine therapy of patients with atrial fibrillation]. AB - Clinical efficacy of and potential risk for complications from combined cordarone+quinidine treatment were studied in 52 patients with atrial fibrillation (AF). Out of 32 patients with a persistent pattern of the disease the sinus rhythm was recovered in 28 (87.5%) of the patients; out of 20 patients with paroxysmal pattern of AF resistant to routine anti-arrhythmic treatment, the sinus rhythm was recovered in 14 (70%) patients. Almost 50% Q-T prolongation was recorded in one patient with paroxysmal AF. Despite the withdrawal of the medication, 4 hours later ventricular tachycardia of the "pirouette" type arose that 2-3 minutes later was followed by ventricular fibrillation with clinical death. After effective electric defibrillation in the presence of lidocaine treatment ventricular fibrillation repeated 7 times. A total of 32 cardiac defibrillations were performed for 6 hours. The normalization of the Q-T interval was observed on the fourth day only. The patient was discharged from the hospital in a satisfactory condition. PMID- 1507843 TI - [Possibility of the evaluation of right ventricular failure in ischemic heart disease based on pulse Doppler ultrasonography of large hepatic veins]. AB - Pulse dopplerography examination of the blood flow rate in the large hepatic veins evidenced the possibility of the assessment of the right ventricular failure. Systolic blood flow appeared to be slow in case of sinus rhythm right ventricular failure, while the acceleration of the blood flow occurred in case of atrial fibrillation. Absolute ratio between the maximal rate of the systolic blood flow and the maximal rate of the diastolic flow of the spectrum of Doppler's frequency of pulse dopplerography of large veins in case of the right ventricular failure was lowered irrespective of the pattern of the cardiac rhythm. PMID- 1507844 TI - [Tactics of management of patients with stomach deformities]. AB - Analysis of gastroscopy in 8781 patients revealed the deformities of the stomach in 1249 (14.2%) patients. Patients younger than 30 had a kink of the stomach and exogastric deformity in 75.5 and 17.7%, respectively. In patients who were older than 70 the respective values were 52.2 and 46.4%. The cause of gastric deformities was stated in 65% of cases (the diseases and specific forms of the adjacent organs). Computed tomography helped to reveal the cause of the deformity in 54% of the cases and ultrasonic investigation in 26% of the cases. The informative value of the used combination of computed tomography and esophagogastroduodenoscopy comprised 75%. PMID- 1507845 TI - [Serum neopterin in hepatitis B]. AB - Activation of the immunity system commonly followed the development of viral diseases. Neopterin is evidently a marker of the activation. Elevation of neopterin levels in AIDS and tumor patients correlates with the severity of the disease. Radioimmunoassay of neopterin content was performed in the sera of 11 patients with virus B hepatitis (6 patients with its acute pattern, 3 with its acute pattern concurrent with delta-infection and 2 subjects with chronic active virus B hepatitis). Mean neopterin content in the sera of virus B hepatitis patients was 19.9 +/- 5.7 nM/l being significantly higher than that in donors (5.0 +/- 0.8 nM/l) (p less than 0.001). In this line neopterin levels higher than 9 nM/l (the upper normal limits) were identified in 63% of the patients. Mean content of beta-2-microglobulin in hepatitis patients was 3.3 +/- 0.53 mg/l being significantly different from that in donors (1.8 +/- 0.3 mg/l) (p less than 0.05). Association between higher neopterin levels and the severity of the disease was fully proved clinically, with the exception of the two expired persons whose neopterin levels were within normal limits. The data obtained evidenced an increase in neopterin levels associated with virus B hepatitis. It widened the understanding of the disease pathogenesis and permitted the determination of neopterin levels be used in correlation with clinical data as a prognostic value for the course of the disease. PMID- 1507846 TI - [Post-transfusion viral hepatitis B and C and criteria of their differentiation]. AB - Two groups of adult patients suffering from posttransfusion viral hepatitis (PTVH) were examined. Group I included 179 patients with PTVH B, group 11 72 patients with PTVH C. Both types of the disease exhibited similar epidemiological, clinical and biochemical serum characteristics, seemed to arise against preexisting diseases. Type C occurred more frequently among females, had shorter latent period, ran a light course. To differentiate between PTVH types B and C, practitioners are recommended to regard duration of the latent period, incidence of acute period HBsAg, anti-HBs, anti-HBc, IgM in the serum, HBs antigenemia occurrence in donors suspected of PTVH induction, history of serologically confirmed viral hepatitis B. PMID- 1507847 TI - [Pulmonary diffusing capacity in patients with chronic renal failure treated by hemodialysis]. AB - Forty-eight patients with chronic renal insufficiency (CRI) receiving hemodialysis (24 males and 24 females) aged 17-62 underwent bicycle exercise to measure diffuse capacity of the lungs (DCL) before and after the test. DCL components (membraneous and blood volume in pulmonary capillaries, Vc) were defined in 33 out of 48 patients. DCL appeared to reduce significantly (up to 65 +/- 2%) at the expense of Vc fall to 51 +/- 4.5% and membraneous component decline, to 65 +/- 4%. DCL depended on severity of anemia, hemodialysis efficiency, electrolyte metabolism activity and CRI gravity. Performance status in CRI patients is limited by DCL value responsible for maximal oxygen consumption under exercise being independent on duration and type of hemodialysis. PMID- 1507849 TI - [Achievements and prospects in renal transplantation]. PMID- 1507848 TI - [Features of correction of phosphate-calcium metabolism disorders in terminal renal failure]. AB - Mineral metabolism was studied in 27 hemodialyzed patients with terminal chronic renal failure (CRF). Because of progressing hyperparathyroidism the initial treatment included calcium drugs, active forms of vitamin D (videchol, oxidevit), almagel, bicarbonate hemodialysis and hemosorption. The condition improved in 8 and stabilized in 12 patients. Conservative treatment was ineffective in 7 patients who consequently underwent total (4 cases) or subtotal (3 cases), parathyroidectomy. The response was achieved in 3, stabilization in 3, the disease advanced in 1 patients. PMID- 1507850 TI - [Extracorporeal shockwave nephro-uretero-lithotripsy]. AB - Extracorporeal shock-wave lithotripsy (ESWL) has been widely introduced in the treatment of nephro-uretero-lithiasis during the last decade as it provides a noninvasive removal of the stones from the upper urinary tracts. The paper covers the history, techniques, indications, contraindications, anesthesia, complications and results of the method. Positive and negative characteristics of ESWL equipment (lithotriptors) are considered. The experience with 5000 lithotripsies led the authors to the conclusion that ESWL does not solve all the problems in the treatment of nephro-uretero-lithiasis and should be introduced only in large clinics practicing actively x-ray endoscopy and equipped with modern endoscopic and ultrasonic urologic units. PMID- 1507851 TI - [Long-term results of dispensarization of patients with chronic glomerulonephritis]. AB - The results of long-term follow-up (from 4 to 25 years) were studied in 1420 patients with chronic glomerulonephritis registered in the city nephrologic service of Leningrad. The relapses ceased in 45.8% and became less frequent in 16% of cases. The survival rate of long-term follow-up patients was significantly higher than of those observed for 2-3.5 years. Long remissions and slowing down of the disease progression were obtained mostly in cases with mild or moderate process activity and seldom in patients with frequent and persisting relapses: Long-term results did not significantly depend on hypertension or nephrotic syndrome but worsened in membrano-proliferative, sclerotic glomerulonephritis and focal glomerulosclerosis due to their inclination to relapse. PMID- 1507852 TI - [A case of giant leiomyoma of the mediastinum]. PMID- 1507853 TI - [A case of malignant course of pulmonary tuberculosis developing presumably on the background of pneumocystis pneumonia]. AB - The paper presents literature data and a clinical case of a rare disease--a malignant run of pulmonary tuberculosis which developed in a prisoner (male, aged 35) with a suspected pneumocystis pneumonia. A fatal outcome terminated fulminant progression of the disease treated with the use of modern effective antituberculosis modalities. PMID- 1507854 TI - [Malignant mesothelioma of the peritoneum and pleura arising in postinfarction cardiosclerosis and chronic pyelonephritis]. PMID- 1507855 TI - [Peculiarities and complexities of questioning the patient in myocardial infarct]. AB - The author depicted several cases of myocardial infarction which onset or preinfarction angina symptoms were taken by the patients for a catarrhal disease. The signs enabling the doctor to exclude the "catarrhal" origin of patient's feelings were indicated. The author suggested that the term of "catarrhal" variant of myocardial infarction onset" should be used as a pattern of its atypical onset. PMID- 1507856 TI - [Clinical variants of infectious endocarditis]. PMID- 1507857 TI - [Multifocal fibrosis (localized systemic sclerosis)]. PMID- 1507858 TI - Degree of hearing loss due to personal stereo use. PMID- 1507859 TI - Is board certification necessary for school health educators? AB - Voluntary certification through the National Board of Professional Teaching Standards currently is being promoted as a mechanism for achieving higher quality instruction in the nation's schools as well as raising the prestige of the teaching profession. This article examines controversies surrounding this movement, including the Board's decision that a teacher's eligibility to be "board certified" in school health does not depend on prior completion of a health education major. The National Board of Professional Teaching Standards believes their assessment approach will be superior to current quality controls. An analysis of existing certification, accreditation, and external review mechanisms, however, does not support this view. Policy formation strategies to ensure continued viability of Certified Health Education Specialist certification mechanisms are offered. PMID- 1507860 TI - The role of the Federal Government in promoting health through the schools: opening statement of Senator William S. Cohen. PMID- 1507861 TI - The role of the Federal Government in promoting health through the schools: opening statement of Senator Carl Levin. PMID- 1507862 TI - The role of the Federal Government in promoting health through the schools: report from the President's Council on Physical Fitness and Sports. PMID- 1507863 TI - The role of the Federal Government in promoting health through the schools: report from the Office of Disease Prevention and Health Promotion. PMID- 1507864 TI - The role of the Federal Government in promoting health through the schools: report from the Department of Agriculture. PMID- 1507865 TI - The role of the Federal Government in promoting health through the schools: report from the Department of Education. PMID- 1507866 TI - The role of the Federal Government in promoting health through the schools: report from the National School Health Education Coalition. PMID- 1507867 TI - Multiple correlates of cigarette use among high school students. AB - A cross-sectional survey research design measured factors related to cigarette use among 2,212 senior high school students. Results showed 14.3% of the sample smoked cigarettes at least occasionally, with 5.3% reporting they were daily smokers. About 12.8% indicated they were ex-smokers. Males and females smoked at almost equal rates, and the percentage of 10th grade student smokers was slightly higher (16.4%) than the percentage of juniors and seniors who smoked. Approximately 22% of Hispanic students, 15% of Caucasian students, and 4.5% of African-American students reported smoking cigarettes at least occasionally. An initial regression analysis used 21 variables to predict cigarette smoking. A more parsimonious regression model (R2 = .28), using variables from the initial regression analysis with significance levels of .01 or less, indicated the most important predictors of cigarette use were ethnic group, attitude toward females who smoke, close friends' use of cigarettes, personal use of marijuana, best friend's use of cigarettes, personal use of alcohol, and school self-esteem. Implications for school health programs are addressed. PMID- 1507868 TI - Risk for unintended pregnancy and childbearing among educable mentally handicapped adolescents. PMID- 1507869 TI - Addressing sexual orientation in a public high school. PMID- 1507870 TI - The development of reactions of the public to warning and emergency situations in France, Greece, and the Netherlands. AB - This article describes the different reactions to emergency warning messages among residents living within a 3-km radius of a hazardous chemical complex and by people living at least 10 km from an industrial site in France, Greece, and the Netherlands. Belief in warning, primary and secondary appraisal, emotional response, and adherence to normal routine were assessed by conducting face-to face interviews in which a four-phase scenario simulating a credible industrial accident was presented. The results showed that respondents who did not reside in the neighborhood of the hazardous site were, in general, more inclined to trust the warning messages than respondents who resided in the neighborhood were. With the exception of primary appraisal, the warning phases evoked very distinct reactions in the respondents from all three countries with regard to warning belief, secondary appraisal, emotional response, and adherence to normal routine. PMID- 1507871 TI - Subjective underemployment and psychosocial stress: the role of perceived social and supervisor support. AB - The purpose of this study was to examine the effects of subjective underemployment on psychosocial stress. The moderator effects of perceived social and supervisor support were also investigated. Data were collected during the summer of 1987 in a public utility governmental agency in the United States. The sample size was 212 with a 71% response rate. Multiple regression analysis was used to examine the relationship between subjective underemployment and psychosocial stress. As expected, the results revealed a significant positive relationship between subjective underemployment and five indexes of psychosocial stress. The interactions between subjective underemployment and social and supervisor support were not significant; however, the relationships were in the expected directions. Supervisor support was positive and significantly related to psychosocial stress, but social support was not. PMID- 1507872 TI - Learned helplessness and explanatory style in Turkish samples. PMID- 1507873 TI - Attitudes toward preventing versus assisting suicide. PMID- 1507874 TI - Identification of AIDS-related and other related attitudes. PMID- 1507875 TI - The role of gender in helping behavior. PMID- 1507876 TI - The influence of war on suicide rates. PMID- 1507877 TI - Self-esteem agreement in the marital relationship. AB - With the use of the circular-causal model of relationship development, this study examined the convergence of the self-esteem of marriage partners over four martial life stages. Three hundred thirty-six married couples in the United States were randomly selected and divided into four life stage groups: younger couples with a child (or children) under age 6; couples with children in school; empty nest couples, in which the wife is in the age range of 45-59 years; and retired couples. Measures of a partner's self-esteem and his or her evaluation of the spouse's self-esteem were taken. The findings demonstrated a convergence of the partners' self-esteem across life stages. PMID- 1507878 TI - Crowding effects of density and interpersonal distance. AB - In this study, Turkish teenagers were the subjects in an investigation of the effects of spatial and social variables on perceived crowding. In Study 1, male and female subjects were presented with diagrams that simulated social situations in which (a) distance between the subject and other persons, (b) number, or density, of subjects, (c) sex, and (d) friendship were systematically varied. Results indicated a significant crowding effect for interpersonal distance but not for density. In Study 2, data from Turkish college students showed that the lack of effect for density on crowding was stable. Friendship and sex of others had significant main and interaction effects. PMID- 1507879 TI - Euthanasia and abortion: personality correlates for the decision to terminate life. AB - The study addresses three research questions: (a) How well do level of conservatism and religiosity predict attitudes toward passive and active euthanasia? (b) What is the relationship between attitudes toward abortion and attitudes toward euthanasia? (c) How do personality variables relate differentially to these attitudes? Subjects were 168 Australian adults (68 men, 100 women). Initial analysis indicated no sex differences in attitudes toward the study's criterion variables. Descriptive statistics indicated general support for active and passive euthanasia and for abortion, although the majority of the respondents were found to be more accepting of passive than of active euthanasia. Multiple regression analyses indicated that level of conservatism was the most consistent predictor of attitudes toward euthanasia and abortion, whereas religiosity was found significantly to predict attitudes toward abortion only. PMID- 1507880 TI - Success strivings and their relationship to affective work behaviors: gender differences. AB - Gender differences in the importance of six life success dimensions and their relationships to job satisfaction, job involvement, and propensity to stay on the job were examined among 756 working women and men in southeast Florida. Results showed that the female participants rated family relationships, personal fulfillment, and security as more important success measures than their male counterparts did, and they rated status/wealth as less important. Professional fulfillment and security were not significantly different. The relationships between measures of success and work behaviors also varied significantly by gender, even after controlling for demographic and job position variables. PMID- 1507881 TI - Meckel's diverticulum and pregnancy. PMID- 1507882 TI - Cold thyroid nodule: predictive value of fine needle aspiration biopsy at surgery. PMID- 1507883 TI - Newborn hydronephrosis with resolution. PMID- 1507884 TI - Synchronized independent lung ventilation in the management of a unilateral pulmonary contusion with massive hemoptysis. PMID- 1507885 TI - Shortness of breath induced by standing. PMID- 1507886 TI - Radiology case of the month. Diverticular disease of the colon (with abscess formation). PMID- 1507887 TI - Interdisciplinary care in a rural HIV treatment center. PMID- 1507888 TI - HELLP! PMID- 1507889 TI - Presidential candidates present their views on health care reform. PMID- 1507890 TI - America's doctors. PMID- 1507892 TI - Conflicts of interest. PMID- 1507891 TI - De Mortuis. PMID- 1507893 TI - [Prevalence of HIV-1 and other sexually transmitted diseases among Spanish prostitutes]. AB - BACKGROUND: Many studies in Western countries point to the high prevalence of HIV infection in groups of prostitutes especially among those using intravenous drugs (IVDA). Furthermore, there appears to be a low but increasing number of heterosexually infected prostitutes. METHODS: A cross-sectional study was carried out in a sample of 374 prostitutes selected by collaborating groups in 11 provinces with the aim of studying the prevalence of HIV and its associated risk factors in Spanish prostitutes. Furthermore, the prevalence of other sexually transmitted diseases (HIV-2, HTLV-I/II, hepatitis B and syphilis), the frequency of different sexual activities and the use of condoms were investigated in this group. The data were collected by interview using a previously tested questionnaire. RESULTS: Serological analysis demonstrated that 54 persons were positive for HIV-1 (16%), none for HIV-2, 1 for HTLV-I/II, 113 for hepatitis B (46%) and 84 for syphilis (25%). The main risk factor for HIV infection was IVDA; 60% of this group was positive vs 3% of the non IVDA (OR = 47.6; confidence interval 18.4-128.0). Consistent condom use in this population is low, although it varies according to the type of relation and sexual partner. Forty-nine percent of the women having vaginal relations with their customers reported using condoms at all times or almost all times vs 36% for anal relations and 22% for oral relations. These percentages were reduced to 10%, 6% and 3%, respectively with private sexual partners. CONCLUSIONS: Studies concerning HIV prevalence and its associated risk factors in Spanish prostitutes should be continued in order to monitor trends in HIV infection and the use of protective measures. PMID- 1507894 TI - [Hepatic changes in patients with isolated immunodeficiency virus infection and AIDS]. AB - BACKGROUND: The aim of the present study was to describe the spectrum of liver disease in isolated infection by the human immunodeficiency virus and in the acquired immunodeficiency syndrome as well as evaluate whether clinical and/or biological data exist to permit specific diagnosis in liver biopsy. METHODS: Liver biopsy was performed in 39 patients with the human immunodeficiency virus (34 via parenteral drug addicts), 22 of whom had established acquired immunodeficiency syndrome. RESULTS: In 29 cases (74%) a specific histologic diagnosis was obtained with the changes most frequently found being the presence of granulomas (11 patients), mainly in patients with stablished AIDS, and chronic active hepatitis non A non B (10 patients), specially in the cases with isolated infection by the human immunodeficiency virus. Obtaining of a specific diagnosis was associated with an increase in GOT and a decrease of the CD4 lymphocytes and the CD4/CD8 quotient (p = 0.002 in all cases). The existence of established AIDS or prolonged fever was associated with the finding of hepatic granulomas (p = 0.02 and p = 0.002, respectively). The increase in GPT, the absence of stablished AIDS and the absence of prolonged fever was associated to the presence of chronic active hepatitis (p = 0.01, p = 0.002 and p = 0.0002, respectively). CONCLUSIONS: In patients with infection by the human immunodeficiency virus liver biopsy provides diagnostic information in a high percentage of cases. The presence of established AIDS, prolonged fever, and hypertransaminasemia may point towards possible histologic diagnosis. PMID- 1507895 TI - [Plasma concentrations of fibronectin in septic, hypovolemic, and cardiogenic shock. Prognostic usefulness of their variation]. AB - BACKGROUND: Fibronectin is a protein with opsonic capacity. Its plasma level is diminished in septic shock. The aim of the present was to study its behavior in other types of shock. METHODS: A prospective study of 60 patients in shock (septic, hypovolemic and cardiogenic) was carried out. Serial plasma levels of fibronectin were determined in these patients over a period of 72 hours. The values of the cases which evolved favorably were compared with the values of those which did not. RESULTS: In all the cases, the plasma levels of fibronectin were diminished within a minimum of approximately 12 hours with a tendency to recovery of initial values being observed within 72 hours, except in cases in which the evolution of the patient was poor. In these cases fibronectin values remained diminished in such statistical significant. CONCLUSIONS: Plasma levels of fibronectin behave similarly in the three types of shock studied (septic, hypovolemic and cardiogenic). Serial determination of fibronectin provides a good prognostic index in patients with shock. PMID- 1507897 TI - [Omeprazole: a step forward in the therapy of acido-peptic disease]. PMID- 1507896 TI - [Different etiology of thyrotoxicosis as a function of previous prevalence of goiter]. AB - BACKGROUND: The high incidence of goiter is believed to modify the characteristics and etiology of thyrotoxicosis. The aim of the present was to study the etiologic types and clinical characteristics of thyrotoxicosis of patients from two areas of different endemic goiter. METHODS: Two hundred twelve patients (184 women and 28 males) were studied with clinical and analytical data of thyrotoxicosis. The patients were consecutively seen in the endocrinology units of two different hospitals over the last 4 years. One hundred eight patients pertained to the area of the Xeral Hospital in Lugo (inland zone) and 104 pertained to the area of the Juan Canalejo Hospital from La Coruna (coastal zone). The clinical data of thyrotoxicosis, thyroxin concentration and thyroid gammagraphies were evaluated. RESULTS: The different etiological types were: Graves disease (GD): Lugo: 20 (19%), La Coruna 57 (55%; p less than 0.001). Toxic multinodular goiter (TMG): Lugo 53 (49%), La Coruna 29 (28%; p less than 0.001). Toxic adenoma (TA): Lugo 23 (21%), La Coruna 13 (13%). Hyperthyroidism by iodine: Lugo: 8 (7%), La Coruna 3 (3%). Other diagnosis: Lugo: 4 (3%), La Coruna 2 (2%). Although the frequency of thyrotoxicosis was much greater in women the percentage distribution of the etiologic types was similar in the two sexes. Symptoms were more frequent in patients with GD with respect to TMG. The presence of auricular fibrillation was more frequent in patients with TMG (38%) than in those presenting GD (4%; p less than 0.01). CONCLUSIONS: Toxic multinodular goiter is the most common cause of thyrotoxicosis in the zones of high endemic goiter. On lowering endemic goiter the percentage of TMG is lowered and that of Graves disease is raised. The symptomatology of thyrotoxicosis is more evident in GD with relation to other etiologic types, but auricular fibrillation is more frequent in TMG. The high prevalence of toxic nodular goiter and hyperthyroidism by iodine suggests the important pathogenic role of the increase of the ingestion of iodine in the form of iodized salt or drugs with iodine. PMID- 1507898 TI - [Sources of information on mortality and morbidity]. PMID- 1507899 TI - [Effects of sleep on chronic obstructive pulmonary disease]. PMID- 1507900 TI - [Palmar fasciitis syndrome and arthritis associated with breast cancer]. PMID- 1507901 TI - [Primary hyperaldosteronism associated with... primary, secondary, or tertiary hyperparathyroidism?]. PMID- 1507902 TI - [Gynecomastia and hyperthyroidism]. PMID- 1507903 TI - [Granulocyte and macrophage colony stimulating factor (GM-CSF) in patients with acquired immunodeficiency syndrome and neutropenia]. PMID- 1507904 TI - [Lyme disease with exclusively neurologic manifestations]. PMID- 1507905 TI - [Behavioral techniques in the treatment of smokers]. PMID- 1507906 TI - [Tetanus in the adult: patients treated a an university hospital]. PMID- 1507907 TI - [Esophagitis caused by fluconazole-resistant Candida albicans: therapeutic failure and in vitro correlation]. PMID- 1507908 TI - [Pyomyositis caused by Staphylococcus aureus]. AB - BACKGROUND: An evaluation of the clinical characteristics and profitability of the diagnostic methods of myositis by Staphylococcus aureus was undertaken in favor of earlier diagnosis and treatment. METHODS: Twenty-eight cases of pyomyositis by S. aureus attended over the last nine years were studied. Inclusion criteria were: 1) compatible clinical manifestations, 2) demonstration of an abscess in CT and/or surgery, 3) isolation of S. aureus in abscess, hemoculture and/or neighboring tissue. RESULTS: Age: 36 +/- 18 years (limits 9 70). Sex: 23 males (82%). Neighboring pathology existed in 11 cases (39%). 5 sacroiliitis (18%), 4 spondyliodiscitis, 2 osteomyelitis. Favoring/predisposing factors: intravenous drug addiction in 11, staphylococcal sepsis in 6, diabetes mellitus in 4, previous surgery in 3, penetrating muscle injury in 3, and parametritis in 1. Fourteen cases (50%) corresponded to primary pyomyositis. The muscle most frequently involved was the psoas/iliacpsoas, followed by near the forearm muscle, spinal, gluteal, and upper pectoral muscles. In 16 cases (57%), only one muscle was involved, in 10 two muscles, and in 2 three groups. The time of clinical manifestation prior to consultation oscillated between 1.5-30 days, being less in cases of primary pyomyositis (p less than 0.0005). All the patients referred fever and local pain, with functional impotence in 26 (93%), general involvement, shivering and perspiration in 24 (86%). All the patients presented pain upon palpation. In 19 (68%) there was an increase in local temperature and in 18 a palpable mass. S. aureus was isolated in 16 hemocultures (sensitivity 57%), in 12 of 13 cultures of neighboring tissue (92%) and in all those aspirated from abscesses (100%). CT demonstrated muscular (thickening and/or destructuration or abscess) and neighboring pathology (if existent) in all cases. All the patients received medical treatment. Evacuating puncture was carried out in 7 cases, and surgical drainage in 23 (82%). Two cases were cured exclusively with medical treatment. Complications were seen in 8 cases (29%) and two patients died of staphylococcal sepsis. CONCLUSIONS: 1) In myositis by Staphylococcus aureus the percentage of primary pyomyositis is considerable. 2) In secondary pyomyositis the most frequent neighboring processes were sacroiliitis and spondylitis. 3) intravenous drug addiction was the most frequent predisposing factor. 4) The time of clinical evolution is variable although less in case of primary pyomyositis. 5) The performance of hemocultures was found to be greater than described and even greater in primary pyomyositis. 6) Abscess cultures and CT are the most efficient microbiological and imaging techniques in the early diagnosis of myositis by S. aureus. PMID- 1507909 TI - [Concentrations of 25-hydroxyvitamin D3 in Antarctica]. AB - BACKGROUND: Ultraviolet B radiation decidedly influences the synthesis of vitamin D and therefore mineral and bone metabolism. It must also be taken into account that a normal unsupplemented diet is usually deficient in this vitamin. Two groups of subjects pertaining to the Spanish Antarctic Expedition 1988-1989 were studied to determine whether special conditions of irradiation and solar exposure found in Antarctica induce alterations in the abovementioned metabolism. METHODS: Each group consisted of 11 healthy males with ingestion of less than 500 mg/day of calcium. The second group was administered vitamin D3 supplements of 1,000 UI/day. Two blood samples were performed at an interval of 22 days during the Antarctic summer to determine calcium, phosphorus, magnesium, parathormone (PTH) and 25-hydroxycholecalciferol [25(OH)D]. RESULTS: Neither group varied in calcemia, phosphoremia or magnesemia. In the first group the 25(OH)D decreased markedly (p less than 0.01) with no variations being observed in PTH. In the supplemented group, and insignificant increase of 25(OH)D was observed which was significant enough to cause a marked decrease in PTH (p less than 0.01). CONCLUSIONS: Subjects passing periods of time in Antarctica should receive vitamin D3 supplementation at doses less than 1,000 UI/day. PMID- 1507910 TI - [Latex myoglobin: a fast early marker in acute myocardial infarction]. AB - BACKGROUND: To evaluate the diagnostic power of serum myoglobin (Mgb) by latex agglutination as a marker in the first hours of acute myocardial infarction (AMI). METHODS: Two hundred forty-eight serum samples from 53 patients admitted to the Coronary Unit (CU) from the Emergency Department (ED) for suspected AMI were studied. The extractions were carried out upon admission and at 4, 8, 12, 18, 24 and 36 hours after the initiation of symptoms. Myoglobin was analyzed by radioimmunoassay (RIA) and by a semiquantitative method of latex agglutination (Rapitex), in addition to creatine kinase (CK) and MB fraction (CK-MB). Sensitivity (S), specificity (E), positive and negative predictive value (PPV) (NPV) and standard efficacy (SE) of the different markers were measured along with the correlation between RIA and latex methods for Mgb. RESULTS: For a prevalence of 83%, the latex test provided S = 81%, E = 8%, PPV = 97%, NPV = 50%, ES = 0.85; CK S = 43% (*), E = 88%, PPV = 97%, NPV = 24% (*) and ES = 0.31 (*) (* = p less than 0.01) and CK-MB S.63% (*), E = 100%, PPV = 100%, NPV = 34% (*) and ES = 0.31 (*) (* = p less than 0.05). The correlation between latex and RIA in the first 4 hours was r = 0.8243 (p less than 0.0001). On performing the 2 tests separated by 2 in the first 4, latex NPV was 100%. CONCLUSIONS: Mgb - latex is the earliest AMI indicator and has greater diagnostic strength in the first hours than CK and CK-MB. It has a good correlation with Mgb-RIA and is simple and rapid to carry out making it specially useful in Emergency Departments and Coronary Units. PMID- 1507911 TI - [Myositis]. PMID- 1507912 TI - [The midnight sun]. PMID- 1507913 TI - [Acquired immunodeficiency syndrome and T-cell non-Hodgkin's lymphoma]. AB - The clinical observation of a 40 years old male presenting acquired immune deficiency syndrome and T-cell non Hodgkin's lymphoma is presented. The patient was treated with COMET-A regimen (cyclophosphamide, vincristine, methotrexate, etoposide and cytarabine) and a complete remission was obtained. PMID- 1507914 TI - [A 60-year-old woman with Sjogren syndrome and persistent abdominal pain]. PMID- 1507915 TI - [Logic or chance?]. PMID- 1507916 TI - [Severe hypokalemic myopathy as presentation form of primary aldosteronism]. PMID- 1507917 TI - [Ambulatory arterial pressure monitoring: towards an unified terminology]. PMID- 1507918 TI - [Foreign body left in the abdomen. Fever of unknown origin 12 years later]. PMID- 1507919 TI - [Thoracic pain as early clinical manifestation of myocarditis caused by varicella]. PMID- 1507920 TI - [Recurrence of Hodgkin's disease 20 years later]. PMID- 1507921 TI - [Salsalate: is it more tolerated than other non-steroidal anti-inflammatory agents?]. PMID- 1507922 TI - [Toxic hepatitis caused by droxicam]. PMID- 1507923 TI - [Toxic hepatitis caused by droxicam]. PMID- 1507924 TI - [Toxic hepatitis caused by droxicam]. PMID- 1507925 TI - Review of electrolyte pharmacokinetics. PMID- 1507926 TI - In vitro magnesium absorption and the role of intestinal motility. AB - Magnesium (Mg) is known as an inhibitor of spontaneously contracting muscular tissues. To increase extracellular Mg in vivo, high doses of Mg must be given orally. Therefore, we investigated the effect of different doses of Mg given from the mucosal side of the small intestine of rats. According to the model of Trendelenburg, a system for the perfusion of isolated small intestine was developed, which allows the simultaneous recording of absorption and muscle contractions. Increasing doses of Mg were applied serosally or intraluminally. Intramulinal Mg did not affect intestinal motility. In contrast, increasing concentrations of serosal Mg resulted in a 50% inhibition of motility at 2.9 mmol/l Mg. This indicates no influence on intestinal motility of high doses of Mg acting from the mucosal side. In further studies, the addition of citric acid or taurocholic acid did not alter Mg absorption. Serosally applied amiloride (1 mmol/l) inhibited absorption, but also resulted in complete loss of motility. Since in this model passive diffusion is the most important mechanism of Mg transport, a direct influence of amiloride on Mg absorption can be excluded. From these data, we conclude that intestinal motility influences absorption--also of ions in aqueous solution--and should therefore be taken into account in absorption studies. PMID- 1507927 TI - Pharmacokinetics of magnesium salts. AB - Due to the widespread use of magnesium (Mg) in human medicine, interest in quantitative enteral absorption rates arose more than 100 years ago. The introduction of the AAS technique and of radioisotopes has stimulated research. Slowly exchanging compartments have not, however, been accessible up until now, and the exact mechanism(s) of enteral Mg absorption is still unclear; hence, the fate of orally administered Mg cannot be followed in detail. The capacity of skeletal Mg stores varies with exogenous Mg supply, consumption, excretion and age. In otherwise healthy subjects, urine Mg levels correlate with exogenous supply. Neglecting the fact that exogenous Mg exchanges with deep Mg stores to a considerable degree, it makes sense to qualitatively study the availability of Mg compounds by relating the amount administered to the amount excreted in the urine, especially after filling deep compartments. Since renal Mg excretion patterns are known to change when tubular reabsorption capacity is exceeded or when pH alterations occur, these parameters must be monitored and taken into account at the quantitative evaluation of data. PMID- 1507929 TI - General aspects of calcium: skeleton dependency on an appropriate calcium supply. PMID- 1507928 TI - Renal elimination of magnesium as a parameter of bioavailability of oral magnesium therapy. AB - Magnesium is an important cation in human physiology, especially in the regulation of membrane proteins, as a cofactor for various enzyme systems and in neuromuscular transmission. Magnesium deficiency leads to severe impairment in muscle function, particularly in cardiovascular diseases. Classical bioavailability studies with magnesium cannot be carried out for several reasons. As the magnesium concentration in plasma is extraordinarily well regulated, renal elimination proves to be the best method to determine the absorption of orally administered magnesium. Magnesium pools must first be filled, and the saturation phase of renal elimination then equals the degree of absorption. This parameter of bioavailability shows the percentage of eliminated magnesium in comparison to the administered dose. Eighteen healthy male volunteers were included in this study to compare 5 mg magnesium-DL-hydrogen aspartate with magnesium-L-hydrogen aspartate. After a saturation phase, the test substances were administered in random order. Blood samples for determination of magnesium concentrations were taken, but no typical pharmacokinetic concentration curves were obtained. The areas under the concentration-time curves were equal for both formulations (x = 40.22 [mval*h/l]). The bioavailability of both substances was determined from the renal elimination. No significant difference was found between both treatments. Bioavailability of 5 mg magnesium-DL-hydrogen aspartate was 44.5% and for magnesium-L-hydrogen aspartate 41.7%. It is evident that this method of magnesium determination is practical, comfortable for volunteers and gives reliable results in comparing the absorption of magnesium formulations. PMID- 1507930 TI - Selenium: nutritional implications and prospects for therapeutic medicine. PMID- 1507931 TI - Water: mechanism of oral rehydration, water deficiency = deficiency in salt. AB - UNICEF, the United Nations International Children Emergency Funds, has staged an enormous program to improve children's health conditions in the developing countries. One extremely fruitful field of engagement was, and still is, the treatment of dehydration. Oral rehydration therapy (ORT) has reluctantly been accepted in the industrialized countries. From clinical observations, we have gained a new understanding of known pathophysiological principles. Dehydration most often is a result of diarrhea, and therefore oral rehydration therapy is mostly referred to in the context of infections of the digestive system. We discuss additional causes of dehydration and its immediate and secondary consequences. We demonstrate not only that, but why and how, a very simple, inexpensive regimen is beneficial and effective in the treatment of dehydration. Without consideration of sodium deficit, understanding will fail, and treatment will remain ineffective. PMID- 1507932 TI - A new method for the rapid determination of ionized Mg2+ in whole blood, serum and plasma. AB - A novel ion selective electrode (ISE) for ionized magnesium (IMg2+) in whole blood (WB), plasma (PL) and serum (S) has now been designed and characterized in normal human subjects, diseased and pregnant subjects. Using this ISE on various levels of aqueous Mg2+ solutions (0.1-3.0mM), mean Mg2+ values are within 94.6 and 99.2% of their targets. The linearity of the ISE (0.1-3.0mM) in aqueous solution and human PL and S ranges between 92.0 and 99.3%. The ISE is highly selective for IMg2+, yielding measurements in less than 2 min, and exhibiting no or negligible effects from physiologic concentrations of Ca2+,Na+,K+ or H+. Ligand binding studies indicate that pathophysiologic concentrations of most smaller molecular weight anions fail to interfere with IMg2+ measurements in aqueous solution, PL or S. Likewise, pathophysiologic concentrations of heavy metals or lipids do not interfere with measurements for IMg2+. Comparison of healthy, normal WB, PL and S IMg2+, using the ISE, with measurements of ultrafilterable Mg by atomic absorption spectroscopy (AAS) are excellent. The mean value for IMg2+ in normal WB, PL and S is 0.58-0.60mM (range = 0.53-0.67mM). Compared to total Mg (TMg) (0.75-0.96mM) and ICa2+ (1.10-1.30mM), IMg2+ is held in a narrow, tight range, representing 71% of TMg. Preliminary studies on plasma and serum IMg2+ during open heart surgery and term pregnancy demonstrate significant abnormalities in IMg2+ and % IMg2+. The new ISE for IMg2+ should prove invaluable and revolutionary in studies of Mg metabolism in both healthy and diseased states. PMID- 1507933 TI - A new method of in vitro prescreening evaluation of several Mg salts. AB - The human amniotic membrane may be considered a model for the prescreening evaluation of the membrane effects of several Mg salts because it is an asymmetrical membrane (polarity of the 2 sides: the ratio between the total ionic conductance Gt both ways and the ratio between the ionic flux from the mother to the fetus (F1) and the ionic flux from the fetus to the mother (F2) are different from 1), samples of which can be obtained without ethical problems, and which is easily usable. Whatever the tested salt, the ratio F1/F2 must be constant or increased without alterations of the ionic fluxes (+/-20%), because a toxic metal (As) has no effect on F1/F2, but strongly decreases the ionic fluxes. To apply this model to the study of the effects of Mg salts, two conditions should be considered: 1) Mg oral therapy: Mg deficit increases the membrane fluidity and the increase of Mg concentration rigidifies the membrane, i.e. decreases Gt; the plasma level of Mg being equal to 1 mM, Mg salts would be tested at 1 mM and Gt should be decreased; and 2) Mg parenteral therapy: the Mg effects should be opposite to those of pollutants and alcohol, which reduce Gt; a dose of 3 mM is chosen and Gt should be increased. The general scheme to study Mg salts is the following: observation of the variation of F1/F2 at 1 mM and of the evolution of Gt, and identical observations at 3 mM. This in vitro prescreening method, indirectly applicable to in vivo effects, gives a classification of Mg salts which may be completed by a study of the 10 components of Gt in the case of identical results for Mg salts. PMID- 1507934 TI - A new method of in vitro prescreening evaluation of the relationship between toxic and common metal ions. AB - The human amniotic membrane, an asymmetrical and nonexcitable epithelium with sites differently situated on the fetal and maternal sides, may be considered a model for investigating the relationship between toxic and common metal ions. The method is based on the observation of the ionic transfer across the amnion, estimated by measuring the total ionic conductance Gt from the mother to the fetus and from the fetus to the mother. It is important to note that opposite effects between two ions are not necessarily correlated with antagonism; indeed, pollutants decrease ionic conductance Gt and Mg increases it, but Mg is not an antagonist of all pollutants. To define antagonism between two ions, the Dixon curves theory should be applied. These curves represent the variation of Gt when the concentration of common metal increases (1 mM, 3 mM), while the concentration of toxic metal is maintained constant (3 concentrations of toxic metal are used). The straight lines obtained are either parallel to each other (noncompetitive inhibition), parallel to the x axis (no interaction between common and toxic metals), or the 3 lines intersect at a common point equal to the inhibition constant. At pharmacological doses, there is competitive inhibition (specific antagonism) between Mg and Cd, Zn and Cd, Ca and Cd, and Mg and Pb, and noncompetitive inhibition between Mg and Hg. This method may rapidly indicate a membrane interaction between common and toxic metals. PMID- 1507935 TI - Heart failure and electrolyte disturbances. AB - Electrolyte abnormalities are a frequent and potentially hazardous complication in patients with heart failure. This may be due to the pathophysiological alterations seen in the heart failure state leading to neurohumoral activation (stimulation of the renin-angiotensin-aldosterone system, sympathoadrenergic stimulation), and due to the complications of therapy with diuretics, cardiac glycosides or ACE inhibitors. Patients with heart failure may exhibit hyponatremia due to a decrease in water excretion, which may be related to the enhanced release of both angiotensin and vasopressin and can be exaggerated by diuretic therapy. Along with potassium and calcium, magnesium influences cardiovascular function. Magnesium and potassium deficiencies play an important role in the development of cardiac arrhythmias. Magnesium is essential for the maintenance of intracellular potassium concentration. Although there are conflicting data regarding the prevalence of hypomagnesemia in patients with chronic heart failure (the values range from 7-37%), multiple studies have documented lower magnesium concentrations in patients with heart failure than in normal controls. As magnesium and potassium are mainly intracellular ions, measurements in serum or plasma are of limited value to assess magnesium status. There was no correlation between the intracellular electrolyte content and the electrolyte levels in plasma, either for mononuclear cells or erythrocytes or for myocardial and skeletal muscle. Loop diuretics (e.g. furosemide) are supposed to cause a substantial loss of both magnesium and potassium in the plasma and intracellular space. The potassium-sparing diuretics amiloride and triamterene are reported to also exert magnesium-sparing effects. Recently, ACE inhibitors have been documented to have important magnesium-conserving actions, possibly via their effect on glomerular filtration. Hyperkalemia, secondary to the use of ACE inhibitors in patients with heart failure, is well documented. Digoxin directly limits the renal tubular reabsorption of magnesium, therefore increasing magnesium excretion. Low magnesium and potassium concentrations increase cardiac glycoside toxicity. In contrast, elevated levels of magnesium decrease the sensitivity of human myocardium to antiarrhythmogenic actions of cardiac glycosides, without affecting maximally developed tension. Moreover, magnesium increases binding affinity of cardiac glycosides to the receptor. The antiarrhythmic action of magnesium is suspected to be mediated by a reduced sensitivity to electrophysiological changes induced by Ca2+, thus indicating Ca2+ antagonistic properties of magnesium. Magnesium deficiency has also been implicated in sudden death, notably in patients with congestive heart failure. Therefore, when treating congestive heart failure, one must consider how to prevent depletion of electrolytes or how to replete potassium and magnesium in deficiency states. PMID- 1507936 TI - Absorption of two oral zinc formulations (Zinkorotat 20/40). PMID- 1507937 TI - [Weak economic reasons for privatization. A small organizational unit is the most important]. PMID- 1507938 TI - [Bleeding ulcer--endoscopic hemostasis is being introduced]. PMID- 1507939 TI - [A new indication for verapamil--secondary prevention after myocardial infarction]. PMID- 1507940 TI - [How much protein do infants need?]. PMID- 1507941 TI - [Streptococci at child day care centers. Risk for unnecessary prescription of antibiotics]. PMID- 1507942 TI - [Behavior and symptoms, difficult to explain, can be caused by reactivated trauma after torture]. PMID- 1507943 TI - [A new reporting system for better evaluation of fertilization in vitro]. PMID- 1507944 TI - [Use of tumor markers is increasing--extensive need for education and information]. PMID- 1507945 TI - [Digitalis in atrial fibrillation--science or well-tested experience?]. PMID- 1507946 TI - [Mental and physical stress influence hemostatic mechanisms]. PMID- 1507947 TI - [Clozapine treatment of schizophrenia caused eosinophilia]. PMID- 1507948 TI - [Local administration of gentamicin caused hearing loss]. PMID- 1507949 TI - [The man behind the syndrome. Xavier Bichat: "Open some bodies and the obscurity disappears and you will see clearly"]. PMID- 1507950 TI - [Interdisciplinary cooperation is needed in the treatment of patients with amalgam problems]. PMID- 1507951 TI - [Traumatic stress. Profitable investment for the future. An emergency group contributes to extended psychological and social care in serious accidents]. PMID- 1507952 TI - [All symptoms within 24 hours after diving should be evaluated by experts in diving medicine]. PMID- 1507953 TI - [Do economic incentives change attitude of health personnel?]. PMID- 1507954 TI - [Presence of physicians at executions can reduce suffering]. PMID- 1507956 TI - [Physician as a psychologist? Need for extensive training]. PMID- 1507957 TI - [Cholesterol and change of diet--a reply]. PMID- 1507955 TI - [The NSAID gastropathy--a new hypothesis on the etiology]. PMID- 1507958 TI - [Need for vaccination of all infants against Haemophilus influenzae]. PMID- 1507959 TI - [New preparations for coagulation disorders]. PMID- 1507960 TI - [Craniotomy is not necessary. Embolization with detachable balloons is the most suitable treatment of direct carotid-cavernous fistulas]. PMID- 1507961 TI - [Molecular epidemiology--applications in cancer research]. PMID- 1507962 TI - [Metabolic angiopathic syndrome--interplay between metabolism and vascular wall]. PMID- 1507963 TI - [Hypertensive patients have varying susceptibilities to salt]. PMID- 1507964 TI - [Different grading of patients' anxiety by physicians and patients]. PMID- 1507966 TI - [An internationally unique study in Linkoping. Photopheresis in newly diagnosed diabetes type 1]. PMID- 1507965 TI - [Old method reevaluated. Paracentesis is effective and safe in the treatment of ascites in patients with liver cirrhosis]. PMID- 1507967 TI - [Risk of peripheral embolization in myocardial infarction with left ventricular thrombosis]. PMID- 1507969 TI - [Can the reality of health care be humane?]. PMID- 1507968 TI - [10 years with HIV/AIDS. New dimensions in old ethical problems. Abolish compulsory testing, impose time-limit on isolation]. PMID- 1507970 TI - [Doping in indoor and outdoor sports is an increasing abuse problem]. PMID- 1507971 TI - [Gender testing in sports--soon only a memory?]. PMID- 1507972 TI - [Analysis of fetal fibronectin in cervical and vaginal secretions can predict preterm labor]. PMID- 1507973 TI - [A study of IVF treatment: misleading polemics on cost effectiveness]. PMID- 1507974 TI - [Treatment of atrial fibrillation--a question]. PMID- 1507975 TI - [A patient secretly nephrectomized]. PMID- 1507976 TI - [Increased frequency of sudden infant death in spite of whooping cough vaccination]. PMID- 1507977 TI - [Liberal treatment with erythromycin is justified in suspected whooping cough]. PMID- 1507978 TI - [Characteristic skeletal lesions in chronic recurrent multifocal osteomyelitis in children]. PMID- 1507979 TI - [Small risk of infection for personnel working with hepatitis C patients]. PMID- 1507980 TI - [Graft versus host reaction--serious threat in bone marrow transplantation]. PMID- 1507981 TI - [Rehabilitation prior the adult life is important but prejudiced attitudes are an obstacle]. PMID- 1507982 TI - [Myoma: uterus can be saved with new therapeutic methods]. PMID- 1507983 TI - [Swedish Society of Medical Ethics. Local ethics groups are needed and challenged with new tasks]. PMID- 1507984 TI - [The men behind the syndrome: Eugen Bamberger and Pierre Marie. They developed the theses of Hippocrates on lung disease as a cause of skeletal changes]. PMID- 1507985 TI - [Pseudoxanthoma elasticum--unusual cause of stroke and eye complications]. PMID- 1507986 TI - [Complex partial epileptic seizures with focal EEG changes during benzodiazepine withdrawal]. PMID- 1507988 TI - [Incidence of cancer increased again in 1989]. PMID- 1507987 TI - [Omeprazole is more cost-effective than ranitidine in reflux esophagitis]. PMID- 1507989 TI - [Why are still so many dying of asthma?]. PMID- 1507990 TI - [Will women receive lower quality coronary care?]. PMID- 1507991 TI - [Tobacco smoking in the presence of children is the main question]. PMID- 1507992 TI - [Nifedipine infusions are effective in transient hypertension in small children and infants]. PMID- 1507993 TI - [Arthroscopy under local anesthesia has many advantages but is not suitable for all]. PMID- 1507994 TI - [Safer diagnosis and better follow up with care programs for patients with asthma and chronic lung diseases]. PMID- 1507996 TI - [Cryptococcal meningitis should be suspected in diffuse cerebral symptoms or indistinct meningitis]. PMID- 1507995 TI - [Misleading analyses of digoxin without standardized rest prior to sampling]. PMID- 1507997 TI - [Strategy for better school environment--inquiry, inspection and technical measurements]. PMID- 1507998 TI - [The number of suicides is decreasing, except among the younger age groups]. PMID- 1507999 TI - [Psychological defense of female alcoholics is similar to psychological defense in depressive women]. PMID- 1508000 TI - [Drug therapy in asthma--guidelines from a group of experts]. PMID- 1508001 TI - [Diagnosis and treatment in primary health care are related to different socioeconomic groups]. PMID- 1508002 TI - [Based on my experience: that is how I treat "prostatitis"]. PMID- 1508003 TI - [The prostatitis syndrome--different diagnoses with similar symptoms]. PMID- 1508004 TI - [3 different investigative authorities recommend quality research to prevent misconduct in Denmark]. PMID- 1508005 TI - [The Wanderjahr of Edward D. Churchill. Excerps from the book by J. G. Scannell, Boston]. PMID- 1508006 TI - [Condylomata acuminata and HIV infections]. PMID- 1508007 TI - [Ultrasound diagnosis in abdominal trauma--how much experience does the surgeon need to perform ultrasonic diagnosis?]. PMID- 1508008 TI - [Anal condylomata acuminata in HIV positive patients]. AB - Since July 1986 we started with following all patients with condylomata acuminata including HIV-testing and human papilloma virus (HPV) identification by DNA-DNA hybridisation (southern blot). Seventy patients are included, 39 of them are seropositive. The ratio male to female is 59 to 11, in seropositives 35 to 4, in negatives 24 to 7. The average age is 28 and 31 years respectively. The number of homosexuals and junkies is significantly higher in seropositives. Seventeen patients are in HIV-stage II, 11 in stage III and 10 in stage IV according to CDC classification. Characteristic for the seropositives was an extensive growth on the rectal mucosa and the very rapid growth of initially subtotally resected lesions in order to prevent stenosis. Sixty-five patients were treated by one stage radical operation with electrocauter. Surprisingly recurrency is more frequent in seronegatives, however, the lesion is much smaller in this group. A hypothesis to explain this observation is brought forward. Postoperative complications occurred only in HIV-stages III and IV. We therefore recommend single shot antibiotic prophylaxis in these patients. The HPV-identification showed no malignancy associated HPV-types in both groups but a higher incidence of HPV 11 in higher HIV-stages which we cannot explain. We conclude from our series that, if operation is indicated, one stage radical electrocoagulation of condylomata acuminata is a necessary procedure in seropositive patients and a save one in negative patients but antibiotic prophylaxis should be given in stage III and IV. Anal condylomata acuminata are a hint for possible HIV-positivity. PMID- 1508009 TI - [How much experience is required for ultrasound diagnosis of blunt abdominal trauma?]. AB - Between July, 1st 1989 and June, 30th 1991, 312 patients were entered into a prospective study concerning the reliability of sonographic evidence in blunt abdominal trauma. There were 231 male and 81 female patients aged between 15 and 88 years (mean: 39.9 years). The sonographic team consisted of one experienced sonographer/surgeon (greater than 4000 examinations) and 3 sonographic beginners (less than 200 examinations at the start of the study). The experienced sonographer and the beginners examined 168 and 144 patients, respectively. Patient distribution to the two groups was done according to the sonographic duty roster without consideration of injury severity. The examination was performed with a mobile ultrasound unit at the surgical intake as part of the primary diagnostic work-up. It consisted of four sonographic views (right and left lateral longitudinal, suprapubic and epigastric transverse view) and took about 2 min. Clinical evidence supporting blunt abdominal trauma could only be found in 64 cases, while in 153 patients physical examination was equivocal due to assisted ventilation or paraplegia. Sensitivity and specificity for the clinical examination amounted to 80.6% and 44.5%, respectively. Sensitivity and specificity for the sonographic finding of intraabdominal liquid were 100% each for the experienced sonographer and 96% and 100%, respectively for the beginners. Organ lesions were demonstrated with a sensitivity and specificity of 45% and 99% by the experienced and 36% and 100% by the beginners. The experienced sonographer misdiagnosed one case of free intraabdominal gas, which could not be corroborated both by clinical and radiological evidence.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1508010 TI - [Traumatic rupture of a kidney transplant in chronic lymphocele]. AB - The lymphocele is a seldom complication after kidney transplantation (2.2% of our patients). This manifestation occurs typically 3-4 months after transplantation, as a late complication it's a rarity. The rupture of a kidney graft because of a trauma is unique in our clinical experience, which contains more than 1200 kidney transplantations. We report the case of a 28-year-old man who had 19 years after transplantation a traumatic rupture of the kidney graft. Because of the trauma a preexistent chronic lymphocele got clinically manifest. The histology of the lymphocele wall shows fatty and collagen tissue with a strong fibrosis. The diagnostic and therapeutic procedure is described. There are different possible relations between the rare problems:--the tight lymphocele carries over the force on the graft--the lymphocele has grown together with the graft at the lower pole and ruptures in this place--a little graft rupture makes a clinical manifest bleeding in the lymphocele because the deficiency of perirenal tissue. PMID- 1508011 TI - [2 cases of life threatening gastrointestinal hemorrhage from Meckel's diverticulum]. AB - Meckel's diverticulum is one of the commonest congenital anomalies of the gastrointestinal tract. Two cases requiring emergency laparotomy due to massive gastrointestinal bleeding are presented. Only at laparotomy the correct diagnosis was established. In the first case a segment of small bowel was resected and diverticulectomy was performed in the second case. Both patients are free of complaints now at 2 and 3 years of follow-up respectively. The genesis of diverticular bleeding, the difficulties of the preoperative diagnosis of the complicated diverticulum and the uncertain indication for operation in cases of uncomplicated diverticulum are discussed and the literature is reviewed. PMID- 1508012 TI - [The arterial blood supply of the tibial and practical consequences]. AB - In the periosteum of the human tibia, the arterial blood supply shows a general sectorial angioarchitecture. There are 4 segments: proximal and distal 1/5, proximal and distal diaphysis. The proximal 1/5 of the tibial periosteum is supplied with blood by the aa. recurrentes tibiales anterior et posterior and the aa. inferiores medialis et lateralis genus. At the proximal diaphysis (next 3/10 of the tibia) periosteal branches arise from the a. tibialis anterior and the a. tibialis posterior. The distal diaphysis (following 3/10 below the middle of the tibia) is nourished exclusively by semicircular rami periostales of the a. tibialis anterior, which move around the bone from both sides and join with each other at the facies medialis. It is the only sector, which is supplied by a single main artery. Concerning the periosteal blood supply of the distal 1/5 of the tibia 2 different types are found. In 2/3 of the cases the lateral side is nourished by a great vessel of the a. fibularis, which is supported by branches arising from the a. tibialis anterior. In 1/3 of the cases this vessel of the a. fibularis is absent and rami periostales of the a. tibialis anterior nourish the lateral aspect of the distal tibia alone. The dorsal region is supplied in all cases by rami of the a. fibularis and a. tibialis posterior. On the medial side the periosteal nourishment is ensured only by anastomoses. Both the facies lateralis and the facies posterior are supplied by direct branches, which arise from the main arteries of the lower leg.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1508013 TI - Complications after an unusual procedure in the treatment of a cervical spine burst fracture. A case report. AB - A 21-year-old man sustained a burst fracture of the 7th cervical vertebral body complicated by a complete loss of sensory and motor functions. He was treated with a pedicled greater omentum flap interposed between the cervical and thoracic spine in a Latin American country. The purpose of this paper is to point out the atypical way of the initial mismanagement. By applying basic principles of fracture management, open reduction and internal fixation was performed resulting in spinal stability which should enhance any chance of recovery of the patient. PMID- 1508015 TI - [Electromyography and functional analytic findings in obstructive disorders of defecation. A contribution to the differentiation of neurogenic and myogenic sphincter damage]. AB - The aim of this study was to get further information about functional results in patients with outlet obstruction. We investigated 27 patients (age between 42 and 74 years) by electromyography (EMG), manometry and radiology with contrast solution. The electromyography, a dynamic investigation method, allows the differentiation between neuronal and muscular malfunctions of the voluntary controlled pelvis muscles. Patients with outlet obstruction should be divided into three groups by EMG diagnosis: One group with neuronal alterations, another group with muscular alterations and one group with neuro-muscular alterations. We obtained marked statistical differences between patients with neuronal or muscular malfunctions in the mean amplitude, the turns per second and the integration of the mean amplitude compared to the control group (14 patients). Patients with only neuronal alterations showed furthermore statistically significant distinctions of the action potential duration from control, whereas the data of patients with muscular malfunctions were significantly different from control in the peak amplitude of the action potentials. 77% of all investigated patients were not able to relax the pelvis muscles during defecation. PMID- 1508014 TI - [Prognostically relevant factors in intra-abdominal infection]. AB - From 1.1.1982-30.9.1989 280 patients were treated for intraabdominal infection at the clinic for general and abdominal surgery. With regard to their prognostic significance, the extent and localization of the peritonitis, abscess formation, the number of failed organ system, patients' age, total protein, thrombocytes and leucocytes were examined in these patients. The most unfavorable prognosis showed diffuse peritonitis with a mortality rate of 47.2%. Subsequent abscessing worsened the prognosis of the illness. There was a close correlation between the number of failed organ systems at the time of hospitalization and mortality. Low total protein content or more so a necessary substitution therapy were linked to a high mortality (less than 4 g%: 81.2% mortality). A low number of thrombocytes and leucocytes and a low total protein in the serum were a sure sign for a complicated process of the illness, with these 2 situations combined, mortality was 100%. The indication for laparotomy and most of all for relaparotomy can be facilitated, if these factors are included in the decision, as their negative change are an indicator for a further existing or imminent postoperative peritonitis. PMID- 1508016 TI - [Obstruction of the left hemicolon: subtotal colectomy, intraoperative lavage or colostomy?]. PMID- 1508017 TI - Intravascular ultrasound guided holmium:YAG laser recanalization of occluded arteries. AB - Current angioplasty devices are limited by arterial wall dissection and perforation, and by early recurrence from inadequate debulking of lesions. This study evaluated intravascular ultrasound (IVUS) as guidance for concentric laser recanalization of arterial occlusions. Twelve, 2-4-cm-long canine iliac artery occlusions were treated at 2 weeks (organizing thrombus) to 12 weeks (firm fibrous lesions) using a Holmium:YAG laser (2,100 nm wavelength) in free running mode, FRM, (250 musec pulse, 5 Hz), n = 9; and Q-switched mode, QSM (200 ns pulse, 6 Hz), n = 3. A 200 microns (n = 2) or 600 microns (n = 10) optic fiber was centered in the artery coaxial to a 5Fr rotating A scan IVUS probe. The fiber was positioned in the center of the artery distal to the lesion and slowly advanced through the obstruction. In 8 occlusions the same fiber was used as a guidewire for passage of either a 1.6-mm-(n = 2) and/or 3.0-mm (n = 6) diameter multifiber catheter (19 x 100 and 19 x 200 microns fibers, respectively) using FRM energy to further debulk the lesion. In all cases, IVUS guidance enabled concentric initial recanalization of occlusions, although 3 vessel perforations resulted from fiber deviation off the center of the lumen at a distance of 2 to 4 cm from the IVUS imaging element. Both QSM and FRM modes ablated tissue, with FRM modes producing more tissue fragmentation and thermal effect. IVUS images accurately diagnosed the location of lesions compared to angioscopic views and pathologic analysis of the specimens.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1508018 TI - Laser treatment of premalignant and malignant squamous cell lesions of the penis. AB - Thirty men with biopsy-proven premalignant or malignant squamous cell lesions of the penis were treated. All had subclinical aceto-white lesions with histologic evidence for human papilloma virus infection. Nineteen patients had penile intraepithelial neoplasia (PIN I and II) and 11 had squamous cell carcinoma. Of these 11 patients, 6 had noninvasive penile intraepithelial neoplasia--carcinoma in situ (PIN III/Tis)--and 5 had invasive squamous cell carcinoma (4 stage T2 and 1 T3). All were treated with laser: CO2 was used for low-stage lesions, Nd:YAG was used alone or in combination with CO2 laser for more histologically advanced lesions, and KTP/532 was used in one patient with squamous cell carcinoma (Tis). Follow-up in 23 patients for up to 2 years showed that all but 1 (stage T3) remained free from penile malignancy. Appropriate laser therapy for all but deeply invasive (T3) tumors controls local disease, producing results that are clinically equal and cosmetically and functionally far superior to partial penectomy. PMID- 1508019 TI - Pathologic changes occurring in the prostate following transurethral laser prostatectomy. AB - Serial gross and histopathologic examinations of the prostate following transurethral laser prostatectomy in the canine model demonstrated an immediate well-demarcated sphere of thermal necrosis measuring 2.7 cm in diameter, which, within 24 hours, had begun liquefaction and was showing multiple areas of cavitation. By the end of the 1st week, the areas of cavitation had coalesced to form a central cavity lined by a narrow layer of necrotic tissue clinging to the thin surviving peripheral belt of prostatic glandular parenchyma. At 3 weeks, the bluish-black discoloration resulting from breakdown of blood in the necrotic tissue had subsided, leaving masses of coagulonecrotic tissue within the central cavity. Within 5 weeks, the ectatic central cavity was lined by transitional epithelium. These postmortem pathologic observations confirm our surgical and clinical impressions of being able to satisfactorily perform an effective transurethral prostatectomy using neodymium:YAG (Nd:YAG) laser photoirradiation. PMID- 1508020 TI - CO2 laser annular thermokeratoplasty: a preliminary study. AB - Since most techniques of refractive surgery currently in use or being developed have the potential for significant side effects, there is a need for investigating alternative procedures. We herein report on the use of a pulsed CO2 laser beam delivered through a pair of complementary axicons to produce a ring of stromal collagen contraction resulting in the flattening of the corneal apex of cadaver eyes. Irradiances of 29 W/cm2 and 23 W/cm2 were used for rings of 5.5 mm and 7.0 mm, respectively. The creation of a ring of 7.0 mm in diameter did not affect the corneal curvature significantly but when the diameter was reduced to 5.5 mm, substantial flattening proportional to the dose of radiation took place. In our system, it was possible to achieve up to 11.3 diopters of mean keratometry flattening (90 joules, 5.5 mm of diameter). In addition, a 1 mm posterior displacement of the corneal dome without histological evidence of closure of the iridocorneal angle was observed. Annular thermokeratoplasty (ATK) may minimize side effects encountered with other refractive procedures since it does not require ablation, incisions, or interaction with the central optical zone. PMID- 1508021 TI - Mid-infrared laser ablation of the cornea: a comparative study. AB - The ablation thresholds and patterns of collateral damage in cornea produced by Er:YAG (2.94 microns) and Er:YSGG (2.79 microns) lasers were measured. Two different pulse durations, 200 microseconds (normal spiking mode) and 100 ns (Q switched mode), were used at both wavelengths. In the normal spiking mode, damage zones of 16 +/- 2 microns and 39 +/- 7 microns and ablation thresholds of 250 +/- 20 mJ/cm2 and 420 +/- 35 mJ/cm2 were measured at 2.94 microns and 2.79 microns, respectively. In the Q-switched mode, damage zones of 4 +/- 2 microns and ablation thresholds of 150 +/- 10 mJ/cm2 were found irrespective of the laser used. The similarity between the results using the Er:YAG and Er:YSGG lasers in the Q-switched mode suggest that either laser can be used with equal effectiveness for corneal trephination. PMID- 1508022 TI - Pulse duration effects on cutaneous pigment. AB - Melanin, an endogenous chromophore in pigment containing cells in skin, is being specifically altered by lasers using the principle of selective photothermolysis (SPT). This implies that a combination of specific laser parameters of wavelength, pulse duration, spotsize, and energy density are required to confine the delivered laser energy to the targeted cells alone. Because the bulk of cutaneous pigment is localized to epidermal basal cells, pigmentary incontinence has been found to occur in skin exposed to laser irradiation. This study demonstrates that pulse duration or exposure time of the laser affect the severity of pigmentary incontinence induced. Pigment granules are more abundant, aggregated, and located deeper in the dermis following exposure to 500 nsec pulse duration than 100 nsec at a wavelength of 504 nm. This relationship appears to be independent of the laser energy density used. PMID- 1508023 TI - Prevention of X-ray-induced late dermal necrosis in the pig by treatment with multi-wavelength light. AB - Low-level light from a multi-wavelength array of light sources has been used to prevent late X-ray-induced dermal necrosis in the pig. Skin fields, measuring 4 x 4 cm on the flank, were irradiated with a single dose of 23.4 Gy of X-rays. This X-ray dose was associated with the development of a 100% incidence of dermal necrosis, 10-16 weeks after irradiation. These irradiated skin sites were subsequently exposed to light of 660, 820, 880, and 950 nm wavelengths from a gallium aluminium arsenide multiple wavelength multidiode cluster probe (Biotherapy Medical Laser, 3ML), three times a week, from 4 to 16 weeks or 6 to 16 weeks after X-irradiation. The skin fields were exposed to the light pulsating at either 2.5 Hz or 5 kHz. With light pulsating at 5 kHz, energy densities of 0.22, 0.54, 1.08 2.16, 4.32, and 10.8 J/cm2 were used. Treatment with light pulsating at 2.5 Hz, 6-16 weeks after X-irradiation, or treatment with light pulsating at 5 kHz, 4-16 weeks after X-irradiation, did not have a significant effect on the incidence or the latency for the development of ischemic dermal necrosis irrespective of the exposure time to light at each treatment. With light pulsating at 5 kHz, no effect of light dose was observed. However, the overall incidence of dermal necrosis was significantly reduced (P = 0.001) to 52% in the X-irradiated fields receiving treatment with 5 kHz light, 6-16 weeks after X irradiation.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1508024 TI - Exogenous chromophores for the argon and Nd:YAG lasers: a potential application to laser-tissue interactions. AB - Chromophore dyes can be employed to modify laser-tissue interaction. A number of dyes have been investigated for their effect on the absorption and transmission of argon and Nd:YAG laser energy by vascular tissue in vitro. Three histological dyes have been assessed as potential chromophores for the argon laser and four infrared dyes for the Nd:YAG. Segments of porcine coronary artery to which dye had been applied were lased (1,064 nm, 2.5 W, 83 W/cm2, 60 s and 488/514 nm, 400 mW, 10.5 W/cm2, 60s) and the tissue temperature measured remotely using an infrared thermometer. In addition, energy transmission was measured with a photodiode and tissue morphological changes assessed histologically. All three argon dyes significantly increased energy absorption (typically 60 degrees C v. 20 degrees C at 60 s, P less than 0.001, 2-way ANOVA). Three of the four infrared dyes behaved similarly (40-70 degrees C v. 20 degrees C, P less than 0.001). All dyes significantly increased the initial rate of rise in tissue temperature during lasing. A reduction in energy transmission was observed for each of the Argon dyes but not for the Nd:YAG dyes. Histological evidence of thermal damage in control tissue first occurred for the argon and Nd:YAG lasers at 800 mW and 7.5 W without chromophore and at 400 mW and 2.5 W with the chromophore, respectively. A number of effective chromophores have therefore been identified at each wavelength. PMID- 1508025 TI - Reduced tumor cell transfer with contact neodymium-yttrium-aluminium garnett laser scalpels. AB - The local recurrence of tumor growth after surgery is thought, in part, to be a consequence of seeding of tumor cells from the primary lesion. This study was directed at determining if the contact Nd:YAG laser provides any advantage over the use of traditional scalpel dissection for tumor resection. Five human tumor tissue culture cell lines were studied in this report. They included MCF-7 (breast), HeLa (cervical), SW-780 (bladder), HT29 (colon), and A549 (lung). Using a scalpel blade or contact laser scalpel (with or without laser energy), the ability to transfer viable cells from dense cell stocks to new tissue culture wells was tested. Using the A549 cell line, the extent that these instruments were able to "seed" tumor cells was also assessed in a soft agar, in vitro, "incision" model. Results from these studies suggest that the contact laser scalpel has a significantly lower potential to transmit tumor cells, when compared to traditional scalpel blades. PMID- 1508026 TI - Laser endoscopic sympathectomy for palmar hyperhidrosis. AB - Hyperhidrosis palmaris is a common disorder among the Orientals. Despite numerous therapeutic modalities in practice, none has proved entirely satisfactory. With the introduction of video-endoscopic surgery, we combined this system with a fiber optic Nd-YAG laser unit, electrocautery, and a laser Doppler flowmeter to design a new and promising therapeutic technique for palmar hyperhidrosis. General anesthesia with alternating one-lung ventilation is essential for a safe and smooth endoscopic sympathectomy. An operating endoscope was introduced into thoracic cavity via the second intercostal space and then attached to a CCD camera video system, which provided clear visibility of the sympathetic trunk in most cases. The proper level of the sympathetic trunk was further confirmed with the aid of vasomotor response of the palmar skin resulting from electric stimulation on the related sympathetic trunk. Finally, the confirmed target was precisely vaporized with a low power Nd-YAG laser through an endoscope. Twenty patients underwent bilateral sympathectomy, mostly on T2 and its adjacent trunk. This technique did not cause any injury to the lung or bleeding. No Horner's syndrome was produced. It provided a precise ganglionectomy on a confirmed target under clear magnified vision. Consequently, a definite and long-lasting therapeutic effect seemed warranted. It was considered to be a relative minor and safe procedure causing minimal discomfort and an almost invisible scar without producing serious complications. It also shortened the operation time and hospital stay remarkably in comparison with other open sympathectomy procedures. PMID- 1508027 TI - Augmentation of the systemic host anti-tumor response through laser excision. AB - This study examines whether primary laser excision results in augmentation of the systemic host anti-tumor response to tumor rechallenge. Single R3230AC mammary tumor implants, (0.5 x 0.5 x 1.0 mm), were grown in 112 female Fisher 344 rats. The animals were randomized. Group S tumors were excised by scalpel. Group E was excised with a Surgistat electrocautery (Valley Labs, Boulder, CO). Group CS was excised with a Sharplan 1100 CO2 laser (Sharplan, Allendale, NJ) at 25 watts (W) continuous wave (CW) (0.2 mm spot size) and the wound was "sterilized" with a 5 mm spot size by gently heating the tissue without blanching. Group K was excised with a KTP/532 laser (Laserscope, San Jose, CA) at 17 W CW using a 400 microns fiber. Group Y was excised with a Sharplan 2100 Nd:YAG laser set at 15W CW using a 0.2 mm clear sapphire tip. A second tumor implant, (0.5 x 0.5 x 1.0 mm), was placed at a remote site 14 days postoperatively. An unoperated control group was implanted. Secondary tumor volumes were measured for 36 days and the mean tumor volumes (MTV) were statistically compared. The MTV in groups CS, K, Y, and E was less than control (P less than 0.01). The MTV in groups CS, K, Y, and E was less than group S, although this was not statistically different. Lasers and cautery appear to increase the host response against subsequent tumor challenge. This study corroborates earlier studies of other modalities. Further studies to determine whether this host sensitization is an immune response and to elucidate the mechanisms of this effect are warranted. PMID- 1508028 TI - Effect of tissue pressure on contact laser insults. AB - The effect of variations in tissue pressure transmitted through contact laser probes during tissue ablation has been investigated. Weights of 10 and 50 g were transmitted through the tip of the probes onto the gastric and colorectal wall. At all laser energies the depth of tissue vaporization was significantly greater at the higher tissue pressure with perforation of the viscus occurring at laser energies above 10 J. The lateral zones of thermal tissue necrosis were not influenced by tissue pressure. Deformation of the wall of the viscus under the pressure of the probe was identified as a sign of excessive tissue pressure likely to result in perforation of any tissue of similar thickness to the normal gastric or colorectal wall. PMID- 1508029 TI - He-Ne laser irradiation of single identified neurons. AB - Silent (LPa2 and LPa3) and spontaneously active (V3, V5, V17) neurons of subesophageal ganglia of Helix pomatia were irradiated via a 125-mm fiber probe with a 10-mW He-Ne laser (lambda = 632.8 nm), and the rate of membrane depolarization, duration of latent period, and probability of spike activity were measured as the functions of light intensity. It was found that silent neurons can not be activated by He-Ne laser irradiation. When the spontaneously active neurons generating spikes every 7-10 min were irradiated in between their spontaneous spikes, the depolarization of membrane and generation of action potentials occurred as a function of light intensity, I. The probability of spike generation increased until the intensity reached 1 W/cm2, and when I = 4 W/cm2 was equal to 1. The depolarization of the membrane had a threshold at I = 0.1 W/cm2, then increased with increasing the intensity, and reached a plateau at I = 0.7 W/cm2 (depolarization rate 0.18 mV/s). Duration of the latent period decreased from 28 s to 17 s when the intensity was increased from 0.05 to 0.3 W/cm2. Further increase of the light intensity, from 0.3 to 1.5 W/cm2, caused a less pronounced change in the duration of the latent period (e.g., latent period equal to 11 s at I = 1.5 W/cm2). PMID- 1508030 TI - Massive air embolism complicating Nd-YAG laser endobronchial photoresection. AB - A 63 year old male underwent 6,900 rads of external radiation for a squamous cell carcinoma of the left main bronchus. Recurrence of the tumor 8 months later was treated with 6,618 joules and patency of the left main bronchus was restored. Four months later, he developed complete atelectasis of the left lung requiring repeat laser. During the procedure he became hypotensive, bradycardic, and hypoxic due to a tension pneumothorax. Although treated promptly with thoracostomy tube drainage, the patient never awakened. CT scan of the brain demonstrated anoxic encephalopathy with air present in the right frontal lobe. Brain death was confirmed by an EEG and cerebral angiogram. Air embolism has been reported in conjunction with diagnostic procedures including therapeutic pneumothorax for tuberculosis, transthoracic needle biopsy of the lung, and positive pressure ventilation with or without pneumothorax. The only reported case of air embolism associated with laser was a small middle cerebral artery cerebro-vascular accident which was self limited. Its mechanism is unclear, but it is suspected to be due to a communication between a pulmonary vein and the atmosphere. A greater volume of air will enter the damaged vessel in the setting of positive pressure ventilation and/or a tension pneumothorax. When neurologic manifestations are present, hyperbaric oxygen therapy is the treatment of choice. Prompt institution in hemodynamically stable patients can minimize neurologic sequelae. PMID- 1508031 TI - Iron chelators in medicine. PMID- 1508032 TI - Learning and judgment. PMID- 1508033 TI - The Regenstrief Medical Record System: 20 years of experience in hospitals, clinics, and neighborhood health centers. PMID- 1508034 TI - Representing medical knowledge: reconciling the present or creating the future? AB - Modern technology has sparked the creation of computing systems that perform many medically related tasks, but communication between these systems is limited, in part by differences in the terminology used for various purposes and in part by the changing nature of medical concepts. The Unified Medical Language System represents an attempt to find a means of translation between diverse knowledge systems. An alternative, which we propose, is to agree on a knowledge base for the future and make use of present accomplishments in moving toward that goal. PMID- 1508035 TI - The ninth annual directory of medical hardware and software companies. PMID- 1508036 TI - The Palmtop computer: medicine's new "peripheral brain". PMID- 1508037 TI - DNA twist as a transcriptional sensor for environmental changes. AB - A variety of reports describe shifts in the environment which cause a corresponding change in the measured linking number of plasmid DNA isolated from bacterial cells. This change in linking number is often attributed to a change in superhelical density. This, coupled with the observation that transcription is often dependent upon the superhelical density of the DNA template seen in vitro, has led to the suggestion that superhelical density may control expression of certain genes. However, since many environmental changes could, in principle, influence DNA twist itself, then the measured differences in linking number, delta Lk, may simply be a consequence of variation in twist according to the relationship delta Lk = delta Tw + delta Wr, where delta Tw and delta Wr are changes in twist and writhe, respectively. In fact, we show that when an environmental change causes a change in the helical pitch of the DNA, and if the superhelical density of DNA is regulated to remain constant according to the homeostatic model of Menzel and Gellert, then delta Lk approximately delta Tw. We have found that there are a number of published reports describing variation in promoter activity as a function of linking number that can be explained by considering twist. We suggest that there are classes of sigma 70 promoters whose ability to be recognized by RNA polymerase is exquisitely sensitive to the relative orientation of the -35 and -10 regions, and environmental conditions can control this relative orientation by changing DNA twist.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1508038 TI - Two linked genes for outer membrane proteins are absent in four non-disease strains of Haemophilus somnus. AB - Linked genes encoding two outer membrane proteins (p76 and a family of proteins, p120) of the bovine pathogen, Haemophilus somnus, were investigated. The p120 group was previously shown to have immunoglobulin-binding activity and to react with polyclonal antiserum specific for a 270 kDa antigen (p270) which also had immunoglobulin Fc-binding activity. By Western blotting we showed that the p76 antigen also reacted with this antiserum. The p270, p120, and p76 antigens were undetectable in four serum-sensitive isolates from asymptomatic carriers but were present in the two serum-resistant virulent strains tested. Genes for p120 and p76 were subcloned on non-overlapping pUC plasmids from a cosmid (pHS1) originally cloned from a serum-resistant strain. In Escherichia coli, plasmid pHS138 expressed p76, while the p120 antigens were produced by pHS140. Southern blots of DNA from the above six strains of H. somnus using probes derived from pHS1 subclones showed that a 13.4 kb sequence was missing from the four serum sensitive strains, but not the two serum-resistant strains. This segment included most of the insert in pHS138 and all of the pHS140 insert. The data indicate that p76 and the p120 proteins are absent from serum-sensitive strains because the coding sequences are missing, raising the possibility of insertion of these genes into the chromosome of both serum-resistant strains, or deletion from the four serum-sensitive strains. PMID- 1508039 TI - Pneumocystis carinii shows DNA homology with the ustomycetous red yeast fungi. AB - Pneumocystis carinii causes life-threatening pneumonia in T-lymphocyte immunodeficient subjects in transplant and oncology units or with acquired immune deficiency syndrome (AIDS). Recent DNA homology studies show P. carinii to be a fungus. To investigate the biology and epidemiology of this parasite further, we elected to determine for it a more precise taxonomic assignment within the fungal kingdom. We screened a wide range of organisms representing the major orders of fungi using DNA amplification and subsequently sequenced a portion of the mitochondrial gene encoding the large subunit ribosomal RNA. Our data show that the opportunistic pulmonary pathogen P. carinii is closely related to the ustomycetous red yeast fungi, a group which includes organisms that are extensively distributed throughout the environment and which release many widely dispersed airborne spores. PMID- 1508040 TI - Identification and characterization of narQ, a second nitrate sensor for nitrate dependent gene regulation in Escherichia coli. AB - In response to nitrate availability, Escherichia coli regulates the synthesis of a number of enzymes involved in anaerobic respiration and fermentation. When nitrate is present, nitrate reductase (narGHJI) gene expression is induced, while expression of the DMSO/TMAO reductase (dmsABC), fumarate reductase (frdABCD) and fermentation related genes are repressed. The narL and narX gene products are required for this nitrate-dependent control, and apparently function as members of a two-component regulatory system. NarX is a presumed sensor-transmitter for nitrate and possibly molybdenum detection. The presumed response-regulator, NarL, when activated by NarX then binds at the regulatory DNA sites of genes to modulate their expression. In this study a third nitrate regulatory gene, narQ, was identified that also participates in nitrate-dependent gene regulation. Strains defective in either narQ or narX alone exhibited no nitrate-dependent phenotype whereas mutants defective in both narQ and narX were fully inactive for nitrate-dependent repression or activation. In all conditions tested, this regulation required a functional narL gene product. These findings suggest that the narX and narQ products have complementary sensor-transmitter functions for nitrate detection, and can work independently to activate NarL, for eliciting nitrate-dependent regulation of anaerobic electron transport and fermentation functions. The narQ gene was cloned, sequenced, and compared with the narX gene. Both gene products are similar in size, hydrophobicity, and sequence, and contain a highly conserved histidine residue common to sensor-transmitter proteins. PMID- 1508041 TI - A developmentally regulated cysteine proteinase gene of Leishmania mexicana. AB - We have isolated a gene encoding a previously unreported class of trypanosomatid cysteine proteinase (CP) from the protozoan parasite Leishmania mexicana. The single-copy gene (lmcpa) [corrected]. has several unusual features that distinguish it from CP genes cloned from the related species Trypanosoma brucei and Trypanosoma cruzi. These include a shorter C-terminal extension of only 10 amino acids and a three-amino-acid insertion, GlyValMet, close to the predicted N terminus of the mature protein. Northern blot analysis showed that the gene is expressed in all life-cycle stages but at higher levels in the amastigote stage in the mammal and in stationary phase promastigote cultures which contain the infective metacyclic form of the parasite. A precursor protein of 38 kDa was detected in amastigotes and stationary phase promastigotes with antisera specific to the LmCPa pro-region, but was barely detectable in early log-phase promastigotes. Anti-central domain antisera recognized the 38 kDa precursor and 24 and 27 kDa proteins. The major CPs of L. mexicana amastigotes, previously designated types A, B and C, were not detected with the antisera, suggesting that the gene codes for a previously uncharacterized CP in L. mexicana. The 24 kDa protein detected by the antiserum has no activity towards gelatin but apparently hydrolyses the peptide substrate BzPheValArgAMC. The relative levels of the 24 and 27 kDa proteins vary between the different life-cycle stages. The results indicate that expression of this CP is regulated at both the RNA and protein level. PMID- 1508042 TI - Evasion of type I and type II DNA restriction systems by IncI1 plasmid CoIIb-P9 during transfer by bacterial conjugation. AB - Transmission of unmodified plasmid CoIIb-P9 by bacterial conjugation is markedly resistant to restriction compared with transfer by transformation. One process allowing evasion of type I and II restriction systems involves conjugative transfer of multiple copies of the plasmid. A more specialized evasion mechanism requires the Ard (alleviation of restriction of DNA) system encoded by CoIIb. The ard gene is transferred early in conjugation and specifically alleviates DNA restriction by all known families of type I enzyme, including EcoK. CoIIb has no effect on EcoK modification but this activity is impaired by multicopy recombinant plasmids supporting overexpression of ard. Genetic evidence shows that Ard protects CoIIb from EcoK restriction following conjugative transfer and that this protection requires expression of the gene on the immigrant plasmid. It is proposed that carriage of ard facilitates transfer of CoIIb between its natural enterobacterial hosts and that the route of DNA entry is important to the restriction-evasion mechanism. PMID- 1508043 TI - NADH formation by Na(+)-coupled reversed electron transfer in Klebsiella pneumoniae. AB - Citrate is fermented by Klebsiella pneumoniae to 2 acetate, 0.5 formate and 1.2 CO2. The formation of less than 1 formate and greater than 1 CO2 per citrate can be accounted for by the oxidation of formate to CO2 in order to provide reducing equivalents for the assimilation of citrate into cell carbon. A membrane-bound electron transport chain is apparently involved in NADH synthesis by these cells. The electrons from formate oxidation to CO2 are used to reduce ubiquinone to ubiquinol by membrane-bound formate dehydrogenase and ubiquinol further delivers its electrons to NAD+, if this endergonic reaction is powered by delta mu Na+. The endogenous NADH level of K. pneumoniae cells thus increased in the presence of formate in response to a delta pNa+ greater than -100 mV. NADH formation was completely abolished in the presence of oxygen or after addition of hydroxyquinoline-N-oxide, a specific inhibitor of the Na(+)-translocating NADH:ubiquinone oxidoreductase. The increase of endogenous NADH was dependent on the delta pNa+ applied to the cells. Inverted membrane vesicles of K. pneumoniae catalysed the reduction of NAD+ to NADH with formate as electron donor after application of delta mu Na+ of about 120 mV consisting of delta pNa+ of 60 mV and delta psi of the same magnitude. Neither the delta pNa+ nor the delta psi of this size alone was sufficient to drive the endergonic reaction. Strictly anaerobic conditions were required for NADH formation and hydroxyquinoline-N-oxide completely inactivated the reaction.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1508044 TI - The divergent promoters mediating transcription of the par locus of plasmid RP4 are subject to autoregulation. AB - The partitioning region of broad-host-range plasmid RP4 contains four genes (parA, parB, parC, and parD) that encode products essential for partition activity. Two divergently arranged promoters located in the intercistronic region between parC and parD mediate transcription of these genes. The transcriptional initiation sites for both promoters were determined by primer extension. Transcriptional fusions were used to show that parA, parB, and parC are combined in an operon, while parD constitutes a separate transcription unit. Both parCBA (genes in order of transcription) and parD are negatively autoregulated at the level of transcription by the gene products of parA and parD, respectively. parD promoter mutants which have become insensitive to repression by parD were isolated. Comparison of wild type and the mutant parD promoter sequences indicated that three short repeats are likely involved in the negative regulation of this promoter. Potentially these sequence elements comprise target sites for the ParD protein. PMID- 1508045 TI - Transcription and autoregulation of the stabilizing functions of broad-host-range plasmid RK2 in Escherichia coli, Agrobacterium tumefaciens and Pseudomonas aeruginosa. AB - The broad-host-range plasmid RK2 has been shown to encode several proteins important for its maintenance within bacterial populations of a number of Gram negative bacteria. Their genes are organized into two operons: parCBA and parD. These operons have been proposed to be transcribed from two divergent promoters, p-parCBA and p-parD, located within a sequence of approximately 150 bases. In this report we identify and characterize the sequences required for regulated transcription from these promoters in Escherichia coli, Agrobacterium tumefaciens and Pseudomonas aeruginosa. Both of these promoters are repressed by their own gene products in the same manner in all three bacteria tested, with ParA functioning as the primary repressor of p-parCBA and ParD functioning as the repressor of p-parD. The binding regions of these proteins were determined through deletion analyses, DNA mobility shift assays, and an examination of the effect of mutations in this region. Based on these observations, the ParA protein appears to bind to either two inverted repeat or two direct repeat sequences, one downstream from the transcriptional initiation site and the other upstream of the p-parCBA -35 box. The ParD protein appears to bind to one inverted repeat sequence, located between the -35 and -10 boxes of p-parD. PMID- 1508046 TI - Negative transcriptional control of iron transport in Erwinia chrysanthemi involves an iron-responsive two-factor system. AB - Systemic virulence of the phytopathogen Erwinia chrysanthemi 3937 requires a functional iron assimilation system which, in this enterobacterium, is mediated by the siderophore chrysobactin and the outer membrane transport protein Fct. We investigated the regulation of this system by iron. No direct similarity with the Escherichia coli fur gene was found. Insertional mutagenesis allowed isolation of a regulatory mutant which expressed chrysobactin and two other high-affinity iron transport systems previously characterized in strain 3937, regardless of the iron level. RNA/DNA hybridization analysis established that regulation of chrysobactin by iron occurs at the transcriptional level. From a wild-type gene library, a recombinant cosmid able to restore normal regulation in the mutant strain was isolated. By generating a series of subclones and mini-Mulac insertions, we identified a regulatory locus (cbr) extending beyond c. 2.5kb which encodes two polypeptides, CbrA and CbrB, with molecular weights of 34,000 and 55,000 respectively. Functional analysis of the locus suggests that the cognate genes cbrA and cbrB are clustered within an operon. Their expression was studied through chromosomal lac gene fusions, in the presence of plasmid-borne wild-type constructions, under high- and low-iron conditions. In summary, the data show that in the presence of iron, cbr negatively regulates the chrysobactin biosynthetic and transport genes, while under conditions of depletion, cbr is subject to negative autogeneous regulation. PMID- 1508047 TI - Characterization of a novel regulatory gene governing the expression of a polyketide synthase gene in Streptomyces ambofaciens. AB - A key step in the biosynthesis of macrolide antibiotics is the assembly of a large macrocyclic lactone ring by a multienzyme protein complex called the polyketide synthase. In the species Streptomyces ambofaciens, the polyketide synthase for the assembly of the 16-membered ring of the macrolide antibiotic spiramycin is encoded by the biosynthetic gene srmG. Here we show that the accumulation of transcripts from the srmG promoter is governed by the regulatory gene srmR, whose predicted product, a 65 kDa polypeptide, is not significantly similar in its deduced amino acid sequence to that of previously reported proteins in the protein databases. The srmR gene product is also required for the accumulation of transcripts from srmX, an additional gene in the vicinity of srmR, but not for the accumulation of transcripts from srmR itself. Interestingly, mutations in srmR prevent the accumulation of transcripts from the spiramycin resistance gene srmB, but this is an indirect consequence of the failure of srmR mutants to produce spiramycin, which is an inducer of its own resistance gene. The possibility that srmR is the prototype for a new class of regulatory genes governing early events in the biosynthesis of macrolide antibiotics is discussed. PMID- 1508048 TI - The role of syllabic and orthographic properties of letter cues in solving word fragments. AB - The present research examined the role of phonological and orthographic properties of cues in mediating the retrieval of words from the mental lexicon. The task required subjects to resolve fragmented words when provided with semantically related cues (e.g., spiteful:---DIC----). Phonological properties of the letter cues were manipulated such that the letters either corresponded to the syllables (e.g., DIC in vindictive) or nonsyllables (NDI) in the word. Orthographic properties of the letter cues were manipulated by selecting letter groups that either co-occurred frequently in the language or did not. In two experiments, results revealed little or no effect of the phonological variable (syllables) but a reliable effect of the orthographic variable (letter-cue frequency). Letter cues with a low frequency of co-occurrence in the language led to better completion of the fragmented words. We interpret these findings as support for models of lexical representation that are based on orthographic properties (e.g., Seidenberg & McClelland, 1989) rather than those based on phonological constraints. PMID- 1508049 TI - Word frequency effects in associative and item recognition. AB - The word frequency effect (WFE) has been taken as evidence that recall and recognition are in some way fundamentally different. Consequently, most models assume that recall and recognition operate via very different retrieval mechanisms. Experiment 1 showed that the WFE reverses for associative recognition, which requires discrimination between intact test pairs and recombinations of study list words from different study pairs. Experiment 2, in which word triples were used, revealed an interaction between word frequency and test type: for item recognition, performance was better for low-frequency words; however, for associative recognition and free recall, performance was better for high-frequency words. In Experiment 3, item recognition was tested: although overall performance was better for low-frequency words, the recognition advantage for items in intact pairs was larger for high-frequency words, suggesting two components in recognition memory. These results imply common mechanisms in recall and recognition. Theoretical implications are discussed within the framework of the SAM model. PMID- 1508050 TI - Age-related differences in the specificity of verbal encoding. AB - A communication paradigm was used as an analogue to cued recall to separate age related differences in encoding and retrieval. Younger and older adults (senders) generated a series of one-word clues that would enable other subjects (receivers) to generate a designated target word. Clue and target generation tasks, analogous to the encoding and retrieval components of cued recall, were conducted in the context of either a strong or a weak associate of the target. Clues generated by older senders were less effective than clues generated by younger senders in enabling receivers to generate targets, especially when clues or targets were generated in the context of a weak associate. A deficit among older receivers was also obtained, especially when a weak-rather than a strong-associate context word was given to the receiver. Older adults experience difficulty with encoding and retrieval tasks that require processing of context-specific information that is not part of the generic information typically associated with a stimulus. PMID- 1508051 TI - The discriminability of remembered magnitudes. AB - Psychometric functions and the associated indices of discriminative performance (i.e., the point of subjective equality [PSE], just noticeable difference, and Weber fraction) were obtained with the method of constant stimuli using perceptual and remembered line-length standards. Three important results were obtained. First, comparisons with a perceptual or a remembered standard were sensitive to variations of absolute stimulus differences with a common ratio; that is, Weber's law was violated. Second, relative to discriminative performance with the longest and shortest remembered standards, comparisons involving mid range remembered standards displayed increased variability in the PSE and inflated Weber fractions, characteristic of a reduction in the quality of the memorial representation. Finally, large and negative time-order errors (TOE) were observed for successive line judgments but not for those involving remembered standards. The implications of these findings for research concerned with the relationships between perception and memory, as well as the TOE phenomenon, are discussed. PMID- 1508052 TI - Hemispheric specialization for categorical and coordinate spatial representations: a reappraisal. AB - The purpose of the present study was to examine Kosslyn's (1987) claim that the left hemisphere (LH) is specialized for the computation of categorical spatial representations and that the right hemisphere (RH) is specialized for the computation of coordinate spatial representations. Categorical representations involve making judgements about the relative position of the components of a visual stimulus (e.g., whether one component is above/below another). Coordinate representations involve calibrating absolute distances between the components of a visual stimulus (e.g., whether one component is within 5 mm of another). Thirty two male and 32 female undergraduates were administered two versions of a categorical or a coordinate task over three blocks of 36 trials. Within each block, items were presented to the right visual field-left hemisphere (RVF-LH), the left visual field-right hemisphere (LVF-RH), or a centralized position. Overall, results were more supportive of Kosslyn's assertions concerning the role played by the RH in the computation of spatial representations. Specifically, subjects displayed an LVF-RH advantage when performing both versions of the coordinate task. The LVF-RH advantage on the coordinate task, however, was confirmed to the first block of trials. Finally, it was found that males were more likely than females to display faster reaction times (RTs) on coordinate tasks, slower RTs on categorical tasks, and an LVF-RH advantage in computing coordinate tasks. PMID- 1508053 TI - Remembering emotional events. AB - Recent experiments have implied that emotional arousal causes a narrowing of attention and, therefore, impoverished memory encoding. In contrast, other studies have found that emotional arousal enhances memory for all aspects of an event. We report two experiments investigating whether these differing results are due to the different retention intervals employed in past studies or to their different categorization schemes for the to-be-remembered material. Our results indicate a small role for retention interval in moderating emotion's effects on memory. However, emotion had markedly different impacts on different types of material: Emotion improved memory for gist and basic-level visual information and for plot-irrelevant details associated, both temporally and spatially, with the event's center. In contrast, emotion undermined memory for details not associated with the event's center. The mechanisms for emotion's effects are discussed. PMID- 1508054 TI - Familiarity, memorability, and the effect of typicality on the recognition of faces. AB - Typical faces are more poorly discriminated on tests of recognition than are atypical faces, an effect suggested to mediate similar findings for attractive or likable faces. We tested the hypothesis that the effect of typicality on recognition is a function of context-free familiarity and memorability, which function in opposition. Two orthogonal principal components were extracted from subjects' ratings of faces for typicality, familiarity, attractiveness, likability, and memorability--one consisting of the ratings of familiarity, attractiveness, and likability, and reflecting context-free familiarity, and the other consisting of the memorability rating. As expected, typicality loaded equally (r approximately .66), but with opposite sign, on both components. In subsequent experiments, both components were found to be significant and additive predictors of face recognition with no residual effect of typicality. General familiarity decreased discrimination, and the memorability component enhanced it, supporting the hypothesis. The results are discussed in terms of the mirror effect. PMID- 1508055 TI - Semantic priming in the pronunciation of words in two writing systems: Italian and English. AB - Semantic priming effects in naming Italian and English words were investigated. Experiments 1 and 2 were in Italian. In Experiment 1, the subjects named a target word, which was either associated with or unrelated to a preceding prime. The results showed semantic priming effects. However, in Experiment 2, in which the same materials occurred in a list that also included pseudowords, priming effects were obtained with the lexical decision task, but not with pronunciation. In Experiment 3, the inclusion of pseudowords in the materials prevented priming effects from occurring in Italian, but not in English. Finally, Experiment 4 indicated that, even in Italian, nonlexical reading was abandoned when a few of the to-be-pronounced items required lexical knowledge for correct stress assignment. The findings suggest that reading normally occurs lexically. The characteristics of the various writing systems, however, are relevant in determining the strategies that people may adopt in unusual circumstances. PMID- 1508056 TI - Interference in memory for tonal pitch: implications for a working-memory model. AB - The degree of interference caused by different kinds of stimuli on memory for tonal pitch was studied. Musically trained and untrained subjects heard a sequence of two tones separated by an interval of 5 sec. The tones were either identical in pitch or differed by a semitone. Subjects had to decide whether the tones were identical or not. The interval was filled with tonal, verbal, or visual material under attended and unattended conditions. The results revealed clear group differences. Musically trained subjects' retention of the first test tone was only affected by the interposition of other tones. In contrast, the performance of musically untrained subjects was also affected by verbal and visual items. The findings are discussed in the framework of Baddeley's (1986) working-memory model. PMID- 1508057 TI - Consistency of perimenopausal estrogen use reporting by women in a population based prospective study. AB - The authors assessed the accuracy of perimenopausal estrogen use reporting by 430 women in a prospective study of bone health risk factors. Data from two time points 5 years apart indicated that 383 (89%) women could consistently report having ever used perimenopausal estrogens or not. Of the 383, 138 reported some lifetime perimenopausal estrogen use; 97 (70%) of these consistently reported duration of use. The age-adjusted relative odds that women would misreport having ever used perimenopausal estrogens was 11.7 (1.3, 100.6) for women with 11-20 years since last use, and 22.2 (1.8, 277.4) for 21+ years. Among women who inconsistently reported ever use of perimenopausal estrogen, the relative odds of reporting use at baseline and never use at follow-up as compared to reporting the converse by women aged 70-75 was 8.1 (1.2, 53.2) times that for women aged 60-69 at follow-up, and increased to 9.6 (1.8, 49.9) for women aged 76-85. This suggests that women can consistently report perimenopausal estrogen use, but accurate report of use declines in women whose last use precedes the interview by over 10 years. Accurate report of duration or dates of perimenopausal estrogen use may be compromised in women of more advanced age. PMID- 1508058 TI - Effects of vaginally-administered oestriol on post-menopausal urogenital disorders: a cytohormonal study. AB - Forty post-menopausal women with urogenital disorders who were inpatients in the same geriatric hospital were treated with oestriol (E3) for 6 weeks. For the first 2 weeks 0.5 mg E3 (Leo AB, Sweden) was administered intravaginally every day. Over the following 4 weeks the patients received the same quantity either once or twice weekly as a maintenance dose. Oestrogen influence on the vaginal and urethral epithelium was assessed by means of the karyopyknotic index (KPI), while the degree of maturation of the vaginal epithelium was estimated visually. Urinary bacteria were cultivated. A pronounced and progressive rise in KPI was seen in both the vaginal and the urethral epithelium following daily E3 treatment. However, neither of the two maintenance dosages was sufficient to sustain the initial maturation of the vaginal and urethral epithelium induced by E3, since the KPI returned to pretreatment values within 4 weeks. The effect of E3 administration on the vaginal epithelium was overestimated by the visual assessment method. No changes were seen in urinary bacteria. Medroxyprogesterone acetate was given before and after E3 treatment. None of the women suffered from withdrawal bleeding. PMID- 1508059 TI - Effect of fever on menopausal hot flashes. AB - Some women report that they have fewer hot flashes when they have a fever. This is the first case of physiological monitoring of hot flashes during fever in a subject with a well documented pattern of frequent hot flashes when afebrile. During fever, there were fewer hot flashes than during afebrile periods, and these hot flashes also tended to be less intense. For most of the period of reduced hot flashes, internal (core) temperature was elevated, above 37.5 degrees C. When the fever broke, hot flashes resumed in a pattern similar to that of afebrile periods. Possible explanations for the reduction in hot flashes during a fever include: (1) a hot flash is triggered, but the characteristic physiological changes do not occur due to competing thermoregulatory drives, (2) the febrile core temperature inhibits whatever it is that triggers a hot flash; or (3) some product of the fever process inhibits the hot flash trigger or masks the physiological changes that occur during hot flashes. PMID- 1508060 TI - Short term effects of SHD 386L and levonorgestrel on bone and mineral metabolism in the postmenopause: a double-blind randomised placebo-controlled trial. AB - Forty-five healthy postmenopausal women participated in a study designed to examine the effects on bone and mineral metabolism of SHD 386L, a new hormone replacement therapy (HRT) regime. This oral preparation delivers 2 mg estradiol valerate daily and 75 micrograms of levonorgestrel from days 17-28 inclusive of a 28-day cycle. The study was double-blind, randomized and placebo controlled. Patients who received SHD 386L exhibited significant falls in plasma calcium, ionised calcium, phosphate and total alkaline phosphatase. No alteration, however, was observed in plasma osteocalcin. No significant changes in mineral metabolism were observed in a parallel group receiving levonorgestrel alone. The results indicate that SHD 386L is likely to be protective to the skeleton through inhibition of bone resorption and that such actions are attributable to the estrogen component. The preparation was well tolerated, compliance was satisfactory and serious adverse affects were not seen. The above biochemical evidence for skeletal protection will require to be supplemented by prospective biophysical evidence of the effect of SHD 386L on bone mineral density. PMID- 1508061 TI - A new methodological approach to the evaluation of quality of life in postmenopausal women. AB - An approach employing a range of standardized questionnaires, which included the Nottingham Health Profile (NHP), the Psychological General Well-Being (PGWB) index and the Mood Adjective Check List (MACL), was used to assess health-related quality of life (QoL) in conjunction with a study comparing two doses of transdermal oestrogen (50 or 100 micrograms/24 h) combined with an oral progestogen (5 mg medroxyprogesterone acetate for 14 days each cycle). In addition to the QoL measures, climacteric symptoms were self-rated and also summarized by means of the Kupperman index. In all, 59 women, median age 52 (39 71) years, who completed 4 months of therapy were evaluated. The use of a battery of standardized questionnaires enabled a comprehensive evaluation to be made of perceived health, well-being and day-to-day functioning. Not only was symptomatic relief, e.g. reduced frequency of sweating episodes, sleep disturbance and hot flushes, observed during treatment, but there were also improvements in terms of sleep, energy and emotions. The frequency of health-related problems associated with paid employment, housework, social life, home life and sex life decreased, indicating enhanced ability to take part in daily activities. The PGWB index showed improvement in the subscales representing well-being, anxiety, depression, vitality, health and self-control, while the mood scales indicated that the women experienced less tension and more satisfaction. Although the results of this study need to be further documented on the basis of a placebo-controlled trial, the findings nevertheless imply that the use of a battery of standardized questionnaires optimizes the possibility of evaluating climacteric complaints reliably before and after treatment. PMID- 1508062 TI - Long-term effect of transdermal hormonal therapy on aspects of quality of life in postmenopausal women. AB - The long-term effect on aspects of quality of life (QoL) of treatment with transdermal oestrogen for 2 weeks followed by transdermal oestrogen/progestogen norethisterone acetate/oestradiol TTS 0.25/0.05 mg/day for the next 2 weeks was investigated in postmenopausal women within the framework of a 1-year seven centre trial. Of the 136 women who were included (mean age 53 +/- 4.8 years), 110 completed the study. Aspects of QoL that are of relevance in the perimenopause and postmenopause were evaluated using the Psychological General Well-Being (PGWB) index, the Women's Health Questionnaire (WHQ) and the Sleep Dysfunction Scale before and after 3 and 9 months of therapy in the oestrogen phase. Climacteric complaints were also assessed by means of the Kupperman Index. Improved well-being, i.e. less anxiety and depression, increased vitality and better self-control (P less than 0.0001) were observed, as well as reduced sleep disturbance (P less than 0.0001). The WHQ showed decreased vasomotor and somatic symptoms, and improved sex life, emotions and cognitive function (P less than 0.0001). Improvement was the same at 3 and 9 months. According to the Kupperman Index, climacteric symptoms were alleviated (P less than 0.0001). Relief of vasomotor symptoms was correlated with improvement in the WHQ (r = 0.82), the PGWB index (r = 0.58, P less than 0.0001) and sleep (r = 0.51, P less than 0.0001). Because of the absence of a placebo control group, the results must be regarded with caution until confirmed in a placebo-controlled trial. PMID- 1508063 TI - [AIDS from the CIA?]. PMID- 1508064 TI - [Low-salt diet in treatment of hypertension]. PMID- 1508065 TI - [Remodelling: ventricular changes after myocardial infarct]. PMID- 1508067 TI - [Risk factors in high dosage vitamin therapy?]. PMID- 1508066 TI - [The postcoital pill]. PMID- 1508068 TI - [Administer zidovudine early or late?]. PMID- 1508069 TI - [Alpha-lipoic acid inhibits HIV replication]. PMID- 1508070 TI - [Treatment of newborn infants at risk for AIDS]. PMID- 1508071 TI - High altitude sickness. PMID- 1508072 TI - [A comparison of the level of resistance and irritability in Anopheles hyrcanus and An. superpictus to insecticides]. AB - The resistance and irritability to malathion, fenitrothion, propoxur and DDT (WHO insecticide impregnated paper) were determined in the endophilic Anopheles superpictus population in Dushanbe and in the exophilic An. hyrcanus population in Parkhar district. An. superpictus proved to be completely susceptible to malathion, fenitrothion and propoxur, low resistant to DDT, and highly or moderately irritable to all the insecticides. On the contrary, An. hyrcanus, was low irritable to insecticides but highly resistant to DDT and moderately resistant to propoxur, while its susceptibility to malathion and fenitrothion remained complete. It is supposed that the nature of adaptation to insecticide pressure is, to a great extent, determined by mosquito endophily or exophily. PMID- 1508073 TI - [Variability in scabies mites Sarcoptes scabiei De Geer (Acariformes, Sarcoptidae) in relation to scabies epidemiology. 1. A statistical model of female variability]. AB - Individual variability of 235 grain mite females from Moscow and the Moscow Province was studied. The data were processed on a computer. Body proportions were used as a representative dimension index. The size of proterosomal scutellum was stable. A map of the chaetoid cover of notum is given, and its variability was studied. Statistical analysis of all signs was made. Frontal chaetoid and sejugal sections and the number of caudal chaetoids are stable. Naked, middle and abdominal chaetoid sections are the most variable. Linear sizes of naked section and the number of chaetoid sets on middle and abdominal sections correlate with the number of undeveloped chaetoids. The statistical model of variability may be useful for populational analysis of Sarcoptes forms in connection with scab epidemiology. PMID- 1508074 TI - [The insecticidal action of the synthetic pyrethroid Decis on the rodent flea]. AB - A new aspect of insecticide action of synthetic pyrethroid "Decis" as a system poison for wild rodent flea control is discussed. Rapid decay of the insecticide gives an opportunity to use it in grain baits in the natural foci of plague. PMID- 1508075 TI - [The ecology of Echinococcus multilocularis (Leuckart, 1863) and E. granulosus (Batsch, 1786) on the Kamchatka Peninsula]. AB - Some aspects of dwelling of Echinococcus multilocularis and E. granulosus populations in the Kamchatka Peninsula were considered. Transformation of their natural foci to natural synanthropic due to enrichment of mammalian fauna, increased human density and rural development was noticed. Main quantitative characteristics of infectivity of the worm definitive and intermediate hosts are presented using literature and the author's own data. A correlation was noted between host density and their infectivity with Echinococcus. PMID- 1508076 TI - [The efficacy of Vermox and albendazole in an experimental model of nippostrongylosis in mice]. AB - Experiments with the model of Nippostrongylus brasiliensis and white outbred mice showed that vermox and albendazole are highly effective anthelmintics in nippostrongyliasis. The ED50 of albendazole for 7 days invasion (adult worms) is 148.9 times higher than for 4 days (fourth instar larvae) and 25.1 times higher than for 2 days (third instar larvae). The ED90/ED10 ratio for albendazole is 1.4, 4.4, and 12.4 at days 7, 4, and 2, respectively. At the adult stage, susceptibility to anthelmintics (vermox and albendazole) increases with age. PMID- 1508077 TI - [Data on the spread of Culex pipiens on the territory of the USSR]. AB - A map of Culex pipiens molestus distribution over the USSR was made using data of sanitary epidemiological stations of various regions of the country, literature and the authors' own data. It was shown that during the last decades (1978-1990) the Cx. p. molestus breeding occurring predominantly in flooded basements of comfortable houses, especially in new built towns and cities, was recorded throughout the European part of the USSR including some subarctic regions. Cx. p. molestus is also widespread in the Asiatic part of the country including Western and Eastern Siberia, southern regions of Far East and the Sakhalin Island and Kamchatka. In the permafrost areas, most of new houses are built on piles without basements and cellars, and it prevents Cx. p. molestus breeding. The dates of appearance of these mosquitos in various parts of the country due to the development of transportation are discussed. PMID- 1508078 TI - [The search for new antiparasitic agents. 10. The synthesis, toxicological and antimalarial properties of nitrogen-containing heterocycles with a 4-(4 alkylpiperazinyl-1) phenylamine substituent (the preparation quinoprazine)]. AB - Synthesis is described and acute toxicity and antimalaria action is studied in new derivatives of quinoline and benzo(g)quinoline containing a 4-(4 alkylpiperazinyl-1)phenylamine substitute. Only the derivatives of benzo(g)quinoline were found to have a high antimalaria effect and to have advantages over the standard agent chloroquine on their tolerance and protective action. One of the compounds, 4-[4-(4-ethylpiperazinyl-1)phenylamino] benzo(g)quinoline, named QUINOPRAZINE, showed some action against Plasmodium berghei chloroquine--resistant infection (isolate LN-K65). This agent was elected for further tests. PMID- 1508080 TI - [An evaluation of the methods for counting sandfly populations]. PMID- 1508079 TI - [A method for collecting and counting the inhabitants of rodent burrows and nests under field conditions]. PMID- 1508081 TI - [Trichocephaliasis (a lecture)]. PMID- 1508082 TI - [Experience with the diagnosis of taeniarhynchiasis caused by the northern isolate of the beef tapeworm by B. E. Rabinovich's method]. AB - It has been shown that the method of B. E. Rabinovich may be used for the diagnosis of infestation caused by the northern isolate of Taeniorhynchus. Bearing in mind biological specificities of the above helminth species, to enhance the efficacy of diagnostics it is advisable to use the technique in combination with the method of Kato. PMID- 1508083 TI - [The possibility of the formation of an opisthorchiasis focus in the lower reaches of the Angara]. PMID- 1508084 TI - [In defense of Dr. E. N. Pavlovskii--the author of the theory of the natural foci of diseases]. PMID- 1508085 TI - [In happy memory of the outstanding Soviet acarologist B. I. Pomerantsev]. PMID- 1508086 TI - A review of the processes by which ultrasound is generated through the interaction of ionizing radiation and irradiated materials: some possible applications. AB - The production of acoustic waves following the absorption of energy deposited by ionizing radiation, with a consequent production of localized thermal spikes has been confirmed by a number of papers published in the physics literature. This paper reviews the basic theory and presents most of the supporting experimental data. Some of the experimental methods used and the results obtained are summarized. In addition to the rather straightforward and routine use of acoustic phenomena produced by ionizing radiation for the detection and measurements of such radiation, there are some special applications that appear to be especially attractive for medical physics. Some of these are unique to ionizing radiation in that the amplitude of the ultrasound wave is proportional to the energy deposited in small volumes at localized sites of these interactions, while others derive from methodologies already in use with nonionizing radiations. The detection and measurement of this ultrasonic radiation could possibly lead to methods for the study of such fundamental phenomenon as track structure, precision localization of therapeutic treatment beams, and even the possible imaging of internal anatomic structures to provide on-line portal images. PMID- 1508087 TI - Considerations regarding the application of capillary optics to medical radiography. AB - The generation of monoenergetic or quasimonoenergetic x-ray spectra has been accomplished by several methods including the use of K-edge filtration, characteristic radiation, crystal monochromators, and multilayer mirrors. In this paper some practical questions are discussed regarding the possibility of obtaining narrow-band spectra using x-ray reflection in glass capillary optics which have been reported recently in connection with the focusing and generation of parallel x-ray beams. Derivation of formulas for double and triple reflection with and without additional K-edge filtration imply that these methods are superior to the use of filtration alone. It is shown that the double reflection scheme is most sensitive to the angular divergence of the beam emanating from the capillary array used to generate the incident parallel beam. Simulations using three reflections predict output spectra which are relatively insensitive to blurring due to angular divergence. A small amount of K-edge filtration in combination with three reflections provides considerable sharpening of the x-ray spectrum. Aside from the spectral selectivity provided by the capillary array, the reduced divergence of the primary transmission may have advantages for scatter rejection in situations where the air gap between the patient and detector is increased by an amount consistent with the resolution requirements of the application. In parallel beam situations, the use of capillary arrays between the patient and detector may also be useful for the rejection of divergent scattered radiation. PMID- 1508088 TI - A digital-radiographic technique for in vitro tissue thickness measurement using iodine displacement. AB - A novel digital radiographic method has been developed for measuring the thickness of a tissue sample by iodine displacement. This simple, accurate method is useful both in medical research and in the comparison of pathological and clinical findings. Radiographic measurements of tissue samples in air suffer from the limitation that the quantity measured depends on the product of both thickness and radiographic attenuation coefficient. This technique allows one to obtain thickness measurements from a digital radiograph of a tissue sample suspended in a bath of radio-opaque contrast agent. The attenuation of the iodinated contrast agent is much higher than that of tissue or calcium. Thus the resulting image is determined largely by the contour of the surrounding bath, and is only slightly influenced by the composition of the tissue. This technique improves both the accuracy and precision of radiographic thickness determination. In this paper the iodine displacement technique is described and the accuracy and precision of thickness measurements in appropriate phantoms are quantified. This technique has been used with both image intensifier and screen-film based imaging systems to obtain thickness maps of calcified human aorta, with precision better than 4% and spatial resolution of 2.5 mm-1. PMID- 1508090 TI - Evaluation of video gray-scale display. AB - Setting up and maintaining video display monitors properly will help to reduce display variation and improve overall presentation of the radiological image. Display monitor gray-scale characteristics were examined using the SMPTE test pattern. This test pattern may be used as a standard for adjusting brightness and contrast. The controls should be adjusted to display the full dynamic range so that the 5% and 95% signal levels in the pattern are visible. Measured luminance on a laboratory workstation used for radiological perceptual experiments, and on the Siemens CT gray-scale monitor was determined to range from 0.17 to 76.0 nit, and 0.17 to 24.66 nit, respectively. These were compared with the range of approximately 17 to 514 nit for a typical film-viewbox combination. Characteristic curves were determined for both monitors, and CRT gammas were 3.34 and 2.48 for the perceptual workstation and CT console, respectively. The display gamma was determined from fitting luminance data to a log-log plot of luminance versus input gray level. The usefulness of the SMPTE test pattern for visual presentation as well as photometric measurement is demonstrated. PMID- 1508089 TI - Computerized detection of clustered microcalcifications in digital mammograms: applications of artificial neural networks. AB - Artificial neural networks have been applied to the differentiation of actual "true" clusters from normal parenchymal patterns and also to the differentiation of actual clusters from false-positive clusters as reported by a computerized scheme for the detection of microcalcifications in digital mammograms. The differentiation was carried out in both the spatial and frequency domains. The performance of the neural networks was evaluated quantitatively by means of receiver operating characteristic (ROC) analysis. It was found that the networks could distinguish clustered microcalcifications from normal nonclustered areas in the frequency domain, and that they could eliminate approximately 50% of false positive clusters of microcalcifications while preserving 95% of the positive clusters, when applied to the results of the automated detection scheme. A large, comprehensive training database is needed for neural networks to perform reliably in clinical situations. PMID- 1508091 TI - High-contrast resolution of CT images for bone structure analysis. AB - The modulation transfer function (MTF) of an imaging system may be used as a figure of merit to assess its geometrical resolution. As such it is often derived from the point spread function (PSF) through a Fourier transformation, or through a FFT in case of digital images. Using the special features of the convolution backprojection algorithm and making some simplifying assumptions about the number of rays, it is shown that the desired MTF is also obtainable without a Fourier transformation of the PSF, different shapes and sizes of the beam-profile are then analyzed, and finally it is shown that calculated and measured MTF functions are in good agreement. The effects of aliasing on the cutoff frequency are also discussed. PMID- 1508092 TI - Two thermal methods to measure the energy fluence of a brief exposure of diagnostic x rays. AB - This paper describes two simple thermal methods for measuring the energy fluence in J/cm2 from a diagnostic x-ray exposure. Both detectors absorb essentially 100% of the radiation and give a signal that is directly proportional to the energy fluence of the x-ray beam. One detector measures the thermal effect when a pulse of x rays is totally absorbed in the pyroelectric detector of lead-zirconium titanate (PZT). The other detector measures the expansion of a gas surrounding a lead disk detector in a photoacoustic chamber. The increased pressure of the gas is transmitted through a 1-mm duct to a sensitive microphone. Both detectors have previously been used to measure the energy fluence rate of continuous x-ray beams in the same energy region using a chopped beam and a lock-in amplifier. Measurement of the energy fluence of a pulse of radiation eliminates the need for the beam chopper and lock-in amplifier and results in a simple, rugged, and inexpensive dosimeter. Either method can be combined with the area of the beam to give an estimate of the imparted energy to the patient from a diagnostic x-ray exposure. PMID- 1508093 TI - A comparison of semiempirical models for generating tungsten target x-ray spectra. AB - Models for the computer generation of tungsten target x-ray spectra proposed by Birch and Marshall [Phys. Med. Biol. 24, 505-517 (1979)] and recently by Tucker, Barnes, and Chakraborty [Med. Phys. 18 211-218 (1991)] are compared. Some basic differences in the equations for the number of bremsstrahlung photons of different energies in the spectra are discussed. The models are compared in terms of their ability to characterize x-ray spectra from constant potential clinical units using three parameter equivalent spectra (EQSPEC) determined from the fit of model generated transmission curves through aluminum to measured data. The Kramers model for x-ray generation is included for completeness. It is shown that two of the models generate very similar x-ray spectra from given transmission curves although the fitting parameters in the EQSPEC characterization differ. PMID- 1508094 TI - A phantom for standardization and quality control in spinal bone mineral measurements by QCT and DXA: design considerations and specifications. PMID- 1508095 TI - A new x-ray and light field superimposition detector. AB - A fast and accurate method to determine the alignment of the diagnostic x-ray and light fields was developed. Following the exposure, the boundaries of an x-ray field are determined by a custom-built x-ray field position detector and indicated by light-emitting diodes. The alignment of the supposed and the actual x-ray fields agree (within +/- 2 mm) with the corresponding results of the film based procedure. PMID- 1508096 TI - Comments on "Survey of tissue-air ratio data: a review of the literature for diagnostic radiology" by John Hale. PMID- 1508097 TI - Two new experimental methods of calculating scatter fraction as a function of depth in scattering media: a comparison study. AB - Two new experimental methods of calculating scatter fraction (SF), as a function of depth, are presented and used in a comparison study. These methods are based on the assumptions that the total point spread function (psft) consists of geometrical (psfg) and scattering (psfs) components, and that the psft and its components are radially symmetric functions. Both methods assume that psfg is a two-dimensional (2-D) Gaussian function. The first proposed method is based on the serial model of the psft. According to the serial model, psfs is also a 2-D Gaussian function. However, the second method is based on the assumption that the psfs is a monoexponential function. Thus the main difference between these two experimental methods is the way in which the psfs is treated. Published data obtained by Monte Carlo simulations compared to the new experimental results shows that for depths less than 5 cm, both new methods yield smaller values for scatter fraction than Monte Carlo simulation or the subtraction method. However, for depths from 5 to 20 cm, the results of these two new methods were very close to the values obtained by both the Monte Carlo simulation and the subtraction method. These two methods have allowed assessment of the scatter fraction with higher accuracy and reliability and reporting data concludes that the new methods are less error sensitive than the subtraction method. PMID- 1508099 TI - Distributed self-capacitance of magnetic resonance imaging birdcage coils. AB - Presented is a theoretical description of the self-capacitance of a low-pass birdcage coil. The problem considered is that the modification of the distributed self-capacitance produced by the electric interaction between the coil and a cylindrical Faraday screen and illustrates the phenomenon of coil self capacitance as well as the influence of Faraday screens. Changes in coil self capacitance produced by the presence of the screens are shown to be consistent with measured shifts in coil resonant frequencies. PMID- 1508098 TI - A fast and accurate algorithm for volume determination in MRI. AB - The determination of volumes in clinical MRI studies are prohibitive because of the time required to compute an accurate volume. Techniques that speed up the calculation are prone to large errors which make most impractical for an accurate diagnosis. A linear filter, called the eigenimage filter, has been developed that separates a desired feature from other features which interfere with its observation in an image. Using the images produced by this technique (eigenimages), the amount of operator interaction required to calculate volumes are significantly reduced. The technique also has the ability to correct for partial volume averaging effects and as a result a more accurate volume can be determined. The technique was applied to a computer simulation and two phantom studies. The time required to calculate the volume was less than 1 min per slice and the errors in accuracy and reproducibility were less than 2% for all studies. PMID- 1508100 TI - The enhancement of radiotherapy verification images by an automated edge detection technique. AB - Adaptive histogram equalization techniques are known to be effective for the enhancement of contrast in portal images acquired during radiotherapy treatments. A significant drawback is the loss of definition on the edges of the treatment field. Analysis of this problem shows that it can be remedied by separating the treatment field from the background prior to the enhancement, and using only the pixels within the field boundary in the enhancement procedure. An edge extraction algorithm has been developed for delineating the treatment field in portal images, and consists of four modules that are applied to the original portal image in sequence. In the first step, edges are enhanced with a derivative of Gaussian operator that assures high response to the field edges relative to anatomical or other edges in the image. Pixels for which the response of the edge operator was the strongest are subsequently connected by an edge following algorithm to produce a raw contour of the field. In the last two steps the contour is refined by converting it into straight line segments and appending to the contour any parts of the field edge that might have been missed out during the initial edge following. The final contour encloses exclusively those pixels that belong to the treatment field, and the adaptive histogram equalization is applied selectively to this region. The combination of edge detection and selective enhancement was shown to produce images of superior contrast on the patient's anatomical features as well as accurate definition of treatment field edges. PMID- 1508102 TI - Polarity effect in plane-parallel ionization chambers using air or a dielectric liquid as ionization medium. AB - A plane-parallel ionization chamber having a sensitive volume of 2 mm3 and using the dielectric liquid tetramethylsilane as the sensitive medium instead of air is described. In the design of the chamber special attention was given to the factors that can cause unwanted currents in the cable, stem, or the chamber dielectric material. The chamber has been tested with respect to the polarity effect in regions of radiation fields where ordinary plane-parallel ionization chambers will often fail. These regions are the build-up region in photon fields, and the region close to the practical range for electrons where nonelectronic equilibrium is significant. Experimental results show that, despite the extremely small ionization volume in the liquid ionization chamber, the polarity effect never exceeds a few tenths of a percent in field positions where well-known commercially available chambers with much less spatial resolution designed for measurements in radiation therapy fields can show polarity effects of 5% to 30%. The origin of spurious currents and how they must be minimized in the design of either a liquid- or gas-filled ionization chamber is discussed. PMID- 1508101 TI - Verification data for electron beam dose algorithms. AB - The Collaborative Working Group (CWG) of the National Cancer Institute (NCI) electron beam treatment planning contract has performed a set of 14 experiments that measured dose distributions for 28 unique beam-phantom configurations that simulated various patient anatomic structures and beam geometries. Multiple dose distributions were measured with film or diode detectors for each configuration, resulting in 78, 2-D planar dose distributions and one, 1-D depth-dose distribution. Measurements were made for 9- and 20-MeV electron beams, using primarily 6 x 6- and 15 x 15-cm applicators at several SSDs. Dose distributions were measured for shaped fields, irregular surfaces, and inhomogeneities (1-D, 2 D, and 3-D), which were designed to simulate many clinical electron treatments. The data were corrected for asymmetries, and normalized in an absolute manner. This set of measured data can be used for verification of electron beam dose algorithms and is available to others for that purpose. PMID- 1508103 TI - Design of parallel plate ion chambers for buildup measurements in megavoltage photon beams. AB - Dose measurements in the buildup region of megavoltage photon beams are most commonly made using parallel plate ion chambers having fixed electrode separation. Fixed-separation chambers generally do not read correctly under such beam conditions because of the contribution to the chamber signal of electrons from the side walls. In this work it is shown that the side wall error can be very large and published correction formulas are not accurate for all beam conditions and chamber geometries. The principal focus of this study has been to determine the design features of a fixed-separation chamber that has negligible side wall error. The approach has been to study, in beams of 60Co, 6 MV, and 18 MV, the response of a specially built ion chamber in which several chamber parameters could be independently varied. The study has shown that the side wall error is primarily dependent on the ratio of the electrode separation to the wall diameter as well as on the wall density and wall angle. Based on these findings the design of a fixed-separation chamber is described which reads to within about 1% of the correct dose. Guidelines are also provided for assessing the suitability of current commercial fixed-separation ion chambers for buildup measurements. PMID- 1508104 TI - Pretransfusion blood irradiation: clinical rationale and dosimetric considerations. AB - The irradiation of blood before transfusion into immunosuppressed patients is an increasingly common technique used to prevent graft-versus-host disease. A technical procedure is described for the calibration of blood irradiators, including the determination of absolute dose rate and relative dose distribution over the blood volume. Results of dose rate measurements on commercially available irradiators indicate differences of +5% to -13% with manufacturer supplied calibrations and variations in the relative dose rate over the irradiation volume from 70% to 180%. The clinical implications of these findings and the need for accurate dosimetry are discussed. PMID- 1508105 TI - Volume-based geometric modeling for radiation transport calculations. AB - Accurate theoretical characterization of radiation fields is a valuable tool in the design of complex systems, such as linac heads and intracavitary applicators, and for generation of basic dose calculation data that is inaccessible to experimental measurement. Both Monte Carlo and deterministic solutions to such problems require a system for accurately modeling complex 3-D geometries that supports ray tracing, point and segment classification, and 2-D graphical representation. Previous combinatorial approaches to solid modeling, which involve describing complex structures as set-theoretic combinations of simple objects, are limited in their ease of use and place unrealistic constraints on the geometric relations between objects such as excluding common boundaries. A new approach to volume-based solid modeling has been developed which is based upon topologically consistent definitions of boundary, interior, and exterior of a region. From these definitions, FORTRAN union, intersection, and difference routines have been developed that allow involuted and deeply nested structures to be described as set-theoretic combinations of ellipsoids, elliptic cylinders, prisms, cones, and planes that accommodate shared boundaries. Line segments between adjacent intersections on a trajectory are assigned to the appropriate region by a novel sorting algorithm that generalizes upon Siddon's approach. Two 2-D graphic display tools are developed to help the debugging of a given geometric model. In this paper, the mathematical basis of our system is described, it is contrasted to other approaches, and examples are discussed. PMID- 1508106 TI - On the spatial resolution of clinical thermometers. AB - In this work the spatial resolution of type T (copper-Constantan) and type K (Chromel-Alumel) multipoint thermocouple thermometers was investigated. For clinical use, thermocouples are usually inserted within catheters to provide easy access, reproducibility, and a sterile environment. The effect of several types of catheter on the ability of these thermometers to accurately resolve thermal gradients was studied. The influence of the number of wire pairs within the multipoint thermometer was also investigated. A mathematical model has been developed to determine the spatial resolving power of these thermometers. Results indicate that type K thermocouples are generally superior to type T and the use of catheters plays a significant role in spatial resolution. Moreover, the use of mineral oil as a thermal coupling agent between the catheter and the thermometer was also found to have some effect. PMID- 1508107 TI - Head-scatter factors and effective x-ray source positions in a 25-MV linear accelerator. AB - The behavior of the effective source position and the correction factor associated with the collimator opening (head-scatter factor) were investigated for the 6- and 25-MV x-ray beams of a linear accelerator. The primary photon fluence was measured in air for square field sizes from 5 x 5 cm to 40 x 40 cm at distances from the nominal source of 80 to 140 cm, for open and wedged fields (wedge angle 60 deg). An inverse-square analysis shows that, for open fields, the effective source position of the accelerator is about the same (approximately 1 cm downstream) at 6 and 25 MV, for all field sizes. For the wedged fields, the effective source position depends on field size and ranges from about 2 to 4 cm. The head-scatter correction factors for given collimator settings were found to be essentially independent of distance at both energies. PMID- 1508108 TI - Measurement of the source size of a 6- and 18-MV radiotherapy linac. AB - The quality of portal imaging is strongly affected by the source size of the radiotherapy machine. The effective source size of the dual-energy clinac 1800 (6 and 18 MV) was measured with a 50 microns wide and 120 mm long slit formed by two tungsten-copper alloy blocks. A series of slit images were obtained by translating the slit horizontally. The images were analyzed using a microdensitometer. The measured data was simulated using an analytical model of the source and its size was derived by a best-fit analysis. For both energies the FWHM was found to be 1.5 +/- 0.1 mm. PMID- 1508109 TI - Dosimetry of ruthenium-106 eye applicators. AB - In view of the importance of clinical applications of ruthenium-106 beta-ray sources for the treatment of choroidal melanoma, experimental, and theoretical approaches are presented for the dosimetry of such sources. The absolute dose and percentage depth dose of ruthenium applicators have been measured with an extrapolation ionization chamber. For a special flat applicator the absolute dose could be measured with an accuracy of +/- 5%, which is determined by the collection efficiency of the extrapolation chamber. The percentage depth dose of concave applicators, employed in the clinical situation, could only be measured at a distance larger than 5 mm due to their geometry and the outer dimensions of the extrapolation chamber. A computer simulation was therefore developed for the absorption and scattering of electrons, taking into account the geometry and materials of the applicator, to predict the percentage depth dose at distances smaller than 5 mm. The calculated and experimentally determined depth doses are in good agreement. With the aid of the computer simulation a depth dose determination for concave applicators can be made for clinically relevant distances less than 10 mm from the source surface with an absolute accuracy of +/ 10%. PMID- 1508110 TI - Ytterbium-169: calculated physical properties of a new radiation source for brachytherapy. AB - Seeds containing radioactive Ytterbium-169 (169Yb) have recently been manufactured for possible application to brachytherapy. Ytterbium-169 emits photons with an average energy of 93 keV (excluding energies less than 10 keV), and decays with a half-life of 32 days. Analytic and Monte Carlo computations have been used to predict physical quantities useful in treatment planning and radiation protection. Analytic calculations based on the primary photon spectrum of 169Yb (excluding energies less than 10 keV) yield an air-kerma rate constant of 0.0427 cGy cm2 h-1 MBq-1, and an exposure rate constant of 1.80 R cm2 mCi-1 h 1 for this radionuclide. Calculated fmed factors are 0.922 cGy/R for soft tissue and 2.12 cGy/R for bone. The first half-value layer in lead is 0.2 mm; the first tenth-value layer is 1.6 mm. Using Monte Carlo simulations, the relative dose distributions around 169Yb seeds (Amersham, prototypes 4 and 5) are provided, and are then compared with those around an 125I seed (3M model 6702). The 169Yb seeds produce more isotropic dose distributions, and for permanent implants, can deliver it at a greater initial dose rate. A value of 1.19 cm-2 was also calculated for the specific dose constant D0, a value which is applicable to both seed types. Radiation protection is not as easily achieved for permanent implants with 169Yb because of the higher energy emissions (vs 125I). However, for temporary implants, Ytterbium-169 may prove to be a useful substitute for 192Ir or 137Cs because of its relatively lower energy emissions. It is concluded that 169Yb merits further investigation, including dosimetry, radiobiological, and clinical studies. PMID- 1508111 TI - Neutron capture therapy with 235U seeds. AB - A combination of brachytherapy and neutron capture therapy has been evaluated using 235U metal seeds and external neutron beam irradiation. When thermal neutrons are absorbed by 235U, high-energy neutrons and gamma rays are produced and some of these deposit energy in surrounding tissue. A Monte Carlo program, using the code MCNP, has been used to evaluate two sizes of 235U seeds in a water phantom. The results of flux suppression around the seeds and dose distributions are illustrated and discussed. The results show that high doses can be delivered in a relatively short time by using 235U seeds with neutron capture therapy. This therapy with multiple needles or seeds can be envisioned as a substitute for traditional brachytherapy to give an effective killing dose. PMID- 1508112 TI - Macroscopic geometric heterogeneity effects in radiation dose distribution analysis for boron neutron capture therapy. AB - Calculations of radiation flux and dose distributions for boron neutron capture therapy (BNCT) of brain tumors are typically performed using sophisticated three dimensional analytical models based on either a homogeneous approximation or a simplified few-region approximation to the actual highly heterogeneous geometry of the irradiation volume. Such models should be validated by comparison with calculations using detailed models in which all significant macroscopic tissue heterogeneities and geometric structures are explicitly represented as faithfully as possible. This paper describes such a validation exercise for BNCT of canine brain tumors. Geometric measurements of the canine anatomical structures of interest for this work were performed by dissecting and examining two essentially identical Labrador retriever heads. Chemical analyses of various tissue samples taken during the dissections were conducted to obtain measurements of elemental compositions for the tissues of interest. The resulting geometry and tissue composition data were then used to construct a detailed heterogeneous calculational model of the Labrador head. Calculations of three-dimensional radiation flux distributions pertinent to BNCT were performed for this model using the TORT discrete-ordinates radiation transport code. The calculations were repeated for a corresponding volume-weighted homogeneous-tissue model. Comparison of the results showed that peak neutron and photon flux magnitudes were quite similar for the two models (within 5%), but that the spatial flux profiles were shifted in the heterogeneous model such that the fluxes in some locations away from the peak differed from the corresponding fluxes in the homogeneous model by as much as 10%-20%. Differences of this magnitude can be therapeutically significant, emphasizing the need for proper validation of simplified treatment planning models. PMID- 1508114 TI - [Long-term follow-up of thrombolytic treatment of acute infarct in combination with acute and elective revascularization]. AB - From March 1983 to June 1986 in 206 patients with acute transmural myocardial infarction, combined intravenous and intracoronary therapy with streptokinase was initiated. After intravenous thrombolysis and randomization in two groups we performed a coronary angiography with selective intracoronary lysis. Infarct related vessels still occluded after intracoronary streptokinase application were opened mechanically in group I. In group II we performed additionally a percutaneous transluminal coronary angioplasty (PTCA) after mechanical recanalisation (occluded vessels) or after thrombolysis (open vessels). In 85 of 87 cases in group II, PTCA could be performed in the acute phase. Elective PTCA was performed in 22 patients of group I (21%) and in nine patients of group II (9%). Up to five years after myocardial infarction, coronary artery bypass grafting (CABG) was necessary in 22 patients (21%) of group I and in 23 patients (22%) of group II. Within four weeks after infarction CABG was performed in 32% and 17% of group I and II respectively. The six-year survival rate was 78% in group I and 82% in group II. Taken all patients together, the six-year survival rate was significantly higher (p = 0.002) for those with early reperfusion (less than or equal to 3.5 h). The survival rates of CABG-patients, PTCA-patients and patients without reperfusion were 91%, 74% and 65% respectively. Streptokinase thrombolysis results, combined with acute or elective PTCA and/or coronary bypass surgery, in a high six-year survival rate after acute transmural myocardial infarction. This rate is about 20% higher than ten years ago. PMID- 1508113 TI - Gadolinium as a neutron capture therapy agent. AB - The clinical results of treating brain tumors with boron neutron capture therapy are very encouraging. Researchers around the world are once again making efforts to develop this therapeutic modality. Gadolinium-157 is one of the nuclides that holds interesting properties of being a neutron capture therapy agent. It is estimated that tumor concentrations of up to 300 micrograms 157 Gd/g tumor can be achieved in brain tumors with some MRI contrast agents such as Gd-DTPA and Gd DOTA, and up to 800 micrograms 157 Gd/g tumor can be established in bone tumors with Gd-EDTMP. Monte Carlo calculations indicate that with 250 ppm of 157Gd in tumor, neutron capture therapy can deliver 2000 cGy to a tumor of 2-cm diameter or larger with 5 x 10(12) n/cm2 of thermal neutron fluence at the tumor. Dose measurements with films and TLDs in phantoms verified these calculations. More extended Monte Carlo calculations demonstrate that neutron capture therapy with Gd possesses comparable dose distribution to B neutron capture therapy. With 5 x 10(12) n/cm2 thermal neutrons at the tumor, Auger electrons from the Gd produced an optical density enhancement on films that is similar to the effect caused by about 300 cGy of Gd prompt gamma dose and may further enhance the therapeutic effects. PMID- 1508116 TI - [Endoscopic implantation of balloon expandable endoprostheses (Strecker stents) in extrahepatic bile duct stenoses]. AB - 22 balloon expandable wire Strecker-stents were implanted endoscopically in 20 patients (eleven women, nine men, mean age 68.3 [44 to 86] years) with malignant (n = 19) and benign (n = 1) bile duct obstruction. In all cases an effective biliary drainage was obtained. To achieve complete drainage repeated balloon dilatation of the inserted stent was often performed. In two cases stent dislocation occurred immediately after implantation. Additional complications were not observed during the first 30 days. During the observation period of maximally 15 months one patient developed an incomplete occlusion of the stent due to tumor compression that could be reversed endoscopically. In a further patient biliary stones caused relapse of cholestatic jaundice. Four patients died from their malignant disease without evidence of stent occlusion. 15 patients continue to live without renewed jaundice. With the mean observation period of 5.5 months (median five months) this corresponds to a patency rate of 95%. The estimated survival rate according to Kaplan-Meier was 87.7% and the estimated mean survival time 11.7 months. These results demonstrate that in patients with extrahepatic bile duct obstruction an effective biliary drainage can be achieved with balloon expandable wire stents. They represent a further progress in the palliative treatment of patients with extrahepatic obstructive jaundice. PMID- 1508115 TI - [Long-term therapy of cystic liver echinococcosis with mebendazole]. AB - Surgery is the therapy of choice in the treatment of infestations with Echinococcus (E.) granulosus and E. multilocularis. Chemotherapy with mebendazole, a benzimidazole derivative, introduced 1976 in the therapy of human echinococcosis, showed good results only in cases of infestation with E. multilocularis. In the cases of liver cysts, caused by E. granulosus, the treatment with mebendazole did not succeed as well. Between 1977 and 1986, 44 patients, suffering from infestations with E. granulosus, were referred to the Clinical Department of the Bernhard-Nocht-Institut. In a retrospective study, the data of seven patients had been evaluated: They had not undergone surgery because of the size of the lesions or because they refused the operative treatment. Receiving mebendazole as the only therapy, they had been treated and followed up for more than four years. Mebendazole was given in a dosage of 50 mg/kg body weight in repeated cycles of one month's duration followed by a treatment-free interval of two months. After a median of 55 months (median 13 effective treatment months) six of the seven patients presented a therapeutical success as demonstrated by ultrasound and computed tomography. The cystic lesions had dissolved or decreased in size considerably. One case showed unaltered findings of the liver lesion. Mebendazole treatment was well tolerated by all patients. If the size of the cystic liver-lesions excludes a curative operative treatment or if the patient refuses surgery, the indication for chemotherapy with mebendazole is given. PMID- 1508118 TI - [Struma therapy today]. PMID- 1508117 TI - [Chronic vomiting: adenocarcinoma of the small intestine]. PMID- 1508119 TI - [Chronic intermittent urokinase therapy in inoperable end-stage coronary disease with therapy refractory angina pectoris symptoms]. PMID- 1508120 TI - [Caloric requirements of intensive care patients]. PMID- 1508121 TI - [The anatomical characteristics of the root furcations in the molar teeth]. AB - The aim of the present study has been to realize a morphometrical and morphological study on the anatomical characteristics of molar teeth root furcations. Two hundred ninety four molars (147 upper and 147 lower teeth), after extraction and elimination of periodontal ligament residuals by trypsin, have been morphometrically evaluated recording the principal anatomical characters of the furcal and radicular region (root and radicular trunk lengths, mesio-distal and vestibulo-palatal diameters at the cementum-enamel junction, inter-radicular angle width and furcal area extension). By the Pearson's correlation test data such obtained were analyzed to verify the existence of statistically significant correlations among the above mentioned anatomical characteristics. Thirty teeth, selected among the most representatives of the whole sample for their anatomical characters, have been morphologically evaluated: 10 by stereo-microscopical examination, 10 by the observation of non-demineralized histological sections and 10 by scanning electron microscopical examination. Results of the morphometrical evaluation showed that from first to second molar the radicular angle, root length and furcal area width undergo a reduction; differently radicular trunk increases his length. On the basis of this results the Authors try to explain data from recent clinical research testifying that second upper molar is the most frequently extracted tooth. In fact a long radicular trunk is associated with a more apical placement of the furcation entrance and this situation, in conjunction with a narrow inter-radicular angle, can obstruct the insertion of therapeutical instruments, justifying the bad prognosis of the second upper molar involved by periodontal disease. The statistical analysis of anatomical data showed a significant correlation (r = -0.46) among radicular trunk length and inter-radicular angle width (in upper first molars; reverse correlation), root length and inter-radicular angle width (r = 0.51) (lower first molars), vestibular-buccal diameter at the cementum-enamel junction and width of mesial and distal furcal angles (r = 0.43) (upper second molars), the extension of furcal area and the wideness of inter-radicular angle (r = 0.89/0.43). These data are in accord with those from other Authors. Morphological analysis showed the high structural complexity of furcal area in molar teeth with the common observation of cemental crests and pulpal accessory canals orifices; these structures can offer a good receptacle to the subgingival dental plaque and can cause difficulties in debridement and therapeutical treatment of the molar furcal region involved by periodontal disease.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1508122 TI - [The orodental findings in the Ehlers-Danlos syndrome. A report of 2 clinical cases]. AB - Ehlers-Danlos syndrome (EDs) is a hereditary disorder of the connective tissue. Its clinical expression is variable and there are many difficulties in recognizing the disease because of the presence of eleven different forms. In this study the authors describe the oral manifestations in two cases of EDs. The children show hyperelasticity of the skin, easy bruisability, hyperextensibility of the joints, several dental manifestations: periodontitis, many caries, supernumerary teeth or hypodontia. PMID- 1508123 TI - [Once a simple handshake was enough]. PMID- 1508124 TI - [Preliminary research on the prognosis of late reimplants with prior conditioning with a fluoridated solution]. AB - The principal factors that affect the prognosis of a posttraumatic reimplantation are the length of the extra-alveolar persistence and the manner in which the extracted tooth is preserved. Both are fundamental for the maintenance of the fiber vitality of the periodontal ligament. The necrosis of these fibers cause ankylosis. It is observed that the conditioning of the radicular surface with fluoride solutions before the reimplantation is likely to slow down the evolution of radicular resorption. To evaluate the effectiveness of such methodology six cases of traumatic extractions, characterized by a length of extra-alveolar persistency (not longer than 24 hours), and unfavorable conditions of the preserved tooth have been treated by conditioning the radicular surface with the Na-fluoride solution before the reimplantation. Another group of reimplantation cases with the same characteristics have been examined without proceeding first to the radicular conditioning. The results of the study, although preliminary, verified the positive influence of the Na fluoride upon the radicular resorption. PMID- 1508125 TI - [Neuromuscular assessment and postural examination in patients with TMJ condylo meniscal incoordination]. AB - The neuromuscular system plays a primary role in the development of a myofascial syndrome of the temporomandibular joint. Patients suffering from this disease very often show changes in muscular functions. In biomechanical clinical pictures of temporomandibular myofascial syndrome the motor apparatus is involved only in the second stage. In order to determine the efficiency of the motor apparatus and to schedule a physiotherapeutic treatment program to improve condylar-meniscus coordination of the joint, an analysis of muscular function associated with postural examination has been performed, and this with a view to evidence possible skeletal changes, with particular regard to the spine. The study has been carried out in a group of healthy individuals in front of an other group of patients affected by the pathology mentioned. PMID- 1508126 TI - [The influence of the "age factor" on periodontal conditions in the diabetic patient]. AB - Conflicting reports exist in dental literature on the relationship of diabetes mellitus to periodontal disease. Among the controversies about this relation, the role played by the age of patient has been widely investigated. Some authors, in fact, reported an increased prevalence and severity of gingivitis and periodontitis in children and young individuals with insulin dependent diabetes mellitus (IDDM) in comparison to healthy subjects, while other researchers were not able to confirm this finding. In particular some authors postulated the hypothesis that the diabetic state could influence periodontal conditions just after the age of 30-35. The aim of the present study has been to verify this hypothesis. One hundred thirty-two subjects participated in this study; among them 66 were IDDM patients and 66 were healthy controls comparable to the diabetics for the main epidemiological features. In particular, control subjects were similar to the diabetics for oral hygiene level in order not to attribute eventually occurring differences by mistake to the diabetic state instead of to a not comparable amount of bacterial plaque present on the teeth. Among 66 IDDM patients 33 were younger than 30 (medium age = 14; extremes: 6-22) and were indicated as DG (young diabetics) group; others 33 were older than 30 (medium age = 45.1; extremes: 31-66) and were indicated as DA (adult diabetics) group. A similar differentiation was made in the control group obtaining, in this way, two subgroups (CG = young controls and CA = adult controls). In the diabetic groups males were 53% while among controls they represented 58%.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1508127 TI - [Flurbiprofen in oral surgery]. AB - Odontic surgery necessitates the very frequent use of additional auxiliary therapy to improve the post-operative symptoms. In fact the injured tissues respond to such surgical operations generally with an infiltrative-type process which is manifested predominantly by pain, pyrexia, oedema and in the more serious cases with total functional incapacity. The therapy for such symptomatology usually consists of NSAID, steroidal anti-inflammatories and/or chemotherapy. The scope of this research was to verify the possibility of utilising, exclusively, a potent non steroidal antiinflammatory whilst evaluating its therapeutic effects on the pain, the pyrexia and the oedema sustained following odontic surgery. The drug under examination was flurbiprofen, a medication with powerful antiinflammatory, analgesic and antipyretic properties whose mode of action, typical of this type of drug, is principally explained by its inhibition of prostaglandins biosynthesis. Moreover, flurbiprofen has been shown to be a potent inhibitor of platelet aggregation and of the migration of leucocytes. It has other pharmacological mechanisms of action but so far these remain insufficiently well explained. For the above mentioned study, 50 patients who had consented to take part were to undergo odontic surgery near to our clinic. They were subdivided into two groups, each consisting of 25 subjects, and each group was assigned an exclusive therapeutic regimen based on flurbiprofen. Patients in the first group were administered a flurbiprofen dose of 300 mg/day, by mouth, commencing on the day preceding the surgery and then on the next 7 consecutive days.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1508128 TI - Preliminary report: medical examiner reports of deaths associated with Hurricane Andrew--Florida, August 1992. AB - On August 24, 1992, at 1:40 a.m. eastern daylight time (EDT), rain bands associated with Hurricane Andrew reached the eastern coast of Florida. At 4:45 a.m. EDT, Hurricane Andrew made landfall 35 miles southeast of Miami at Homestead, with sustained winds of 145 miles per hour (mph) and gusts of 164 mph. These winds extended 45 miles outward of the storm center. The storm moved across the state at 18 mph toward the Gulf of Mexico (Figure 1). The tidal surge on the eastern coast was estimated at 7-19 feet. During the storm, approximately 2.5 million Florida residents were left without electrical power, and approximately 56,000 family dwelling units were destroyed or severely damaged. This report presents preliminary data from Florida medical examiner (ME) offices about deaths attributed to Hurricane Andrew. PMID- 1508129 TI - Syphilis--Ford County, Kansas, 1992. AB - In January 1992, the Ford County (Kansas) Health Department received a report of a pregnant women with a positive serologic test for syphilis. Syphilis had not been reported in the county (1990 population: 27,463) since September 1989. As a result of the investigation summarized in this report, six additional persons with syphilis were identified by contact tracing. PMID- 1508130 TI - Public health focus: effectiveness of smoking-control strategies--United States. AB - In 1990, approximately 46 million adults in the United States continued to smoke; however, more than 44 million persons were former smokers (1) who had reduced their risk for the leading causes of death in the United States (2). Smoking cessation methods can be categorized as 1) self-help strategies (e.g., quitting abruptly and completely ["cold turkey"], using quitting manuals, or using nonprescription drugs) or 2) assisted strategies (e.g., smoking-cessation clinics, hypnosis, acupuncture, or nicotine gum or patch with counseling). This report summarizes information regarding the efficacy and cost-effectiveness of smoking-cessation strategies. PMID- 1508131 TI - Reporting of race and ethnicity in the National Notifiable Diseases Surveillance System, 1990. AB - Since 1989, all state health departments have reported cases of infectious diseases to the National Notifiable Diseases Surveillance System (NNDSS) through the National Electronic Telecommunications System for Surveillance (NETSS) (1). Electronic reporting allows reporting of additional information, including demographic data, that can be used to help define the scope of public health problems for different groups and to develop appropriate preventive interventions. This report describes reporting through NNDSS of notifiable diseases by patients' race/ethnicity for 1990. PMID- 1508132 TI - [An experimental study on the rejection phenomenon of multi-visceral allografts in pigs]. AB - Multi-visceral allografts including the liver, pancreas and gastrointestinal tract were transplanted in 10 pigs. Eight of them survived for 7 to 21 days. Histopathological changes were studied in the liver, pancreas and gastrointestinal tract. An en bloc transplantation revealed no particular course after transplantation than those individual organ transplantation. The status of rejection was assessed by our histological criteria, which are divided into 5 grades about the liver and 4 grades about other organs according to the severity of the acute rejection. A higher grade of rejection was apparently in the small and large intestine especially after the 10th post-transplanted day (Grade II to III in the small and large intestine v. Grade 0 to II in the liver, stomach and pancreas). The study suggests the existence of organ specific susceptibility to rejection in multi-visceral organ transplantation. PMID- 1508133 TI - [Experimental study for lymphatic routes of the cardia and diaphragm]. AB - We report discovery of the lymphatic routes in the gastric cardia and adjacent diaphragm after producing a blockage in the descending lymphatic route in dogs. CH40 black carbon hydrate was injected into the cardia portion during operation followed by total gastric and diaphragm combined resection to investigate lymphatic routes. In the 12 dogs with a blockage, and an ascending route to the lower mediastinum was recognized in 4 cases, and lateral routes from the hiatus of the esophagus to the diaphragm in a further 3 of the 12 cases. The lateral route was considered to be a collateral lymphatic route of neo-lymphatic vessel. Further, we found that phrenic lymphatic flows went in multiple directions, whereas the lymphatic flow at the phrenic lumbar vertebrae went mainly in the direction of the esophageal opening or aortic opening, although there was some expansion to the mediastinal side or celiac side. Consequently, it was assumed that metastasis to the lateral direction besides the ascending route might occur in cases with cancer in the cardiac portion infiltrating to the hiatus of the esophagus. PMID- 1508134 TI - [Clinicopathological and immunohistochemical studies on carcinoma of the papilla of Vater]. AB - The non-invasive adenomatous component (nac) was observed in 44% of 32 resected specimens of carcinoma of the papilla of Vater. Incidence of the "nac" positive carcinoma declined with cancer staging, but there was no significant relationship between the "nac" and tumor size. The "nac" positive rates in "tumor forming", "ulcerating" and "mixed" types were 65, 0 and 38%, respectively. The "nac" negative carcinoma metastasized more frequently to the lymph nodes, duodenum, pancreas and veins. The five year survival rates of the patients with the "nac" positive and negative carcinoma were 78 and 22%, respectively. Immunohistochemically, the "nac" positive carcinoma mostly showed partial distribution of CA19-9, while the "nac" negative carcinoma, carcinoma of the pancreas and bile duct mostly showed diffuse distribution. The intact mucosa of the common channel and orifice of the papilla almost showed partial distribution, and duodenal mucosa showed negative distribution. The pancreatic and bile duct almost indicated diffuse distribution. The "nac" may be precancerous condition and the "nac" positive carcinoma may arise from the common channel or the orifice of the papilla or the duodenum. But the "nac" negative carcinoma may belong primarily to carcinoma of the pancreas and bile duct as de-novo carcinoma. PMID- 1508135 TI - [Mitochondrial energy synthesis during cold preservation and after reperfusion in liver transplantation]. AB - In liver transplantation, primary graft nonfunction (PGN) occurred 5 to 10% in all cases. For preventing PGN it is necessary to elucidate a reliable assessment procedure for graft function before transplantation. In addition, methods of harvest or preservation which can maintain good viability of the graft are also needed. The purpose of this study is to clarify whether mitochondrial respiratory ratio (RCR), which is ability of ATP synthesis, is a reliable marker of the graft viability and whether a harvesting method with an artificial heart and lung is effective for keeping high energy synthesis of mitochondria or not. Pigs were used for this study. In a standard harvest method RCR decreased gradually during cold preservation. Grafts with values of RCR more than 3.0 had good function after transplantation. RCR depended on mitochondrial ATP, not tissue ATP. Grafts harvested with artificial heart and lung kept RCR more than 4.0 at 12 hours after preservation. Five of 6 pigs transplanted 12 hours preserved liver harvested from the donor with an artificial heart and lung survived more than 5 days. These results suggested that mitochondrial ATP synthesis has strong relation to PGN and RCR is a reliable marker for graft viability. PMID- 1508136 TI - [Effects of preoperative transcatheter portal embolization (TPE) on prevention of hepatic failure after massive hepatectomy]. AB - Effects of TPE on prevention of hepatic failure after massive hepatectomy were studied experimentally using dogs. A 70% or 85% hepatectomy (Hx) was performed two weeks after TPE. All of the 70%Hx groups with(+)/without(-) TPE were alive for over two weeks after hepatectomy. While all of the 85%Hx group without TPE died, eight of ten in the 85%Hx group with TPE survived. Without TPE, total bilirubin levels in sera were elevated markedly in the 85%Hx group and moderately in the 70%Hx group after hepatectomy. The levels of escaped enzymes in sera, such as GOT or GPT, were also elevated remarkably in the TPE(-) groups. Although the levels of these enzymes were also high in the 85%Hx.TPE(+) group, these values were as same as those of 70%Hx.TPE(-) group. In the 85%Hx.TPE(-) group, critical diminution of functional hepatic cell mass and severe portal hypertension occurred after hepatectomy and coagulopathy and death followed to these phenomena. TPE might prevent the onset of these critical phenomena, and diminish the damage caused by massive hepatectomy. These results suggest that TPE is useful for prevention of postoperative hepatic failure so that we could perform massive hepatectomy safely, and extend the operative indication. PMID- 1508137 TI - [An experimental study on development of gallstone disease after curative gastrectomy for cancer--postoperative alteration of the composition of canine gallbladder bile after subtotal gastrectomy with truncal vagotomy]. AB - In connection with gallstone (GS) formation after gastrectomy for cancer, we examined alteration of the composition of gallbladder bile after subtotal gastrectomy with truncal vagotomy. Of 11 mongrel dogs with cholecystostomy, 3 underwent B-I and 4 B-II gastrectomy. Four dogs without gastrectomy were served as controls. Bile was collected for 12 months. Bile acids were quantified by GLC. The bile was cultured for bacteriology. TBA did not significantly differ among the three groups of the dogs. In the two gastrectomized groups, CDA (a secondary bile acid) kept a higher level and CA (a primary bile acid) maintained a lower concentration compared with those in the controls. A remarkable increase of non conjugated bile acids was recognized in both gastrectomized groups. Lithogenicity was low for all of the 3 groups. All but 1 control dog incurred bile infection that persisted long. Black pigment stones containing calcium bilirubinate developed in 1 of the 3 B-I and 2 of the 4 B-II dogs but none in the controls. The bile infection seemed to be involved in the development of GS. As the alteration of bile composition and GS occurred solely in the gastrectomized dogs, subtotal gastrectomy with truncal vagotomy might precipitate the GS formation. PMID- 1508138 TI - [The effect of portal venous drainage on graft survival and function in rat whole pancreaticoduodenal transplantation]. AB - A whole pancreaticoduodenal transplant model with portal venous drainage was achieved in the rat, and effect of venous drainage from pancreas grafts into the portal vein on the functional graft survival and long-term glucose metabolism was investigated. In allogeneic series between ACI (RT1a) donors and streptozotocin induced diabetic Lewis (RT1l) recipients (nonfasting plasma glucose greater than or equal to 400 mg/dl), the mean survival time of pancreas transplants determined by recurrent hyperglycemia (greater than or equal to 200 mg/gl) in rats with portal venous drainage (PV-group: 8.9 +/- 1.3 days) was slightly longer than that in rats with systemic venous drainage (SV-group: 8.3 +/- 0.9 days), but statistically insignificant. In the syngeneic series using Lewis rats, K-values (%/min) in IV-GTT at 1, 2 and 3 months after pancreas transplantation were, respectively, 1.5 +/- 1.0, 2.0 +/- 0.6 and 2.3 +/- 0.7 in PV-group, and 1.2 +/- 0.3, 1.2 +/- 0.4 and 1.8 +/- 0.5 in SV-group. Peripheral IRI (microU/ml) levels before glucose load were higher in both groups (PV-group, 15.1 +/- 10.5: SV group, 22.8 +/- 16.2) at 3 months than in normal control (7.9 +/- 1.6: p greater than 0.05). These results indicate that the portal venous drainage in pancreas transplants has no remarkable profit in graft survival and that it can provide more physiological glucose control but cannot normalize insulin concentration. PMID- 1508139 TI - [Does L-thyroxine administration in a dose to suppress TSH secretion induce metabolic bone disturbance in patients with thyroid carcinoma?]. AB - We investigated whether L-thyroxine for TSH suppression may induce metabolic bone disturbance, especially in trabecular bone. Subjects were 75 premenopausal women (mean age: 37.7) who underwent surgery at Ito Hospital or Yokohama City University Hospital from 1972 to 1988 for differentiated thyroid carcinoma. All of them received L-thyroxine for the purpose of TSH suppression. According to the duration of the drug therapy after surgery, they were divided into 3 groups: Group I patients were treated for more than 10 years after surgery (17 cases), Group II from 5 to 10 years (28 cases), and Group III less than 5 years (30 cases). The control group was consisted of 15 premenopausal women (mean age: 37.0). There was no significant difference in age among these 4 groups. Quantitative CT was used for evaluation of trabecular bone mineral content. Mean bone mineral contents determined in Group I, Group III, Group II and control group patients were 204.7, 213.1, 207.6, 222.6 mg/cm3, respectively. There was no significant difference among them. It is concluded that L-thyroxine can be administered safely without metabolic disturbance in trabecular bone. PMID- 1508140 TI - [An immunological study of changes in the thymus with aging]. AB - Immunological changes of the thymus with aging were studied in human thymic lymphocytes that were obtained from 48 patients undergoing open heart surgery at the 2nd Department of Surgery, Tottori University Hospital. Flow cytometric analysis indicated significant reductions in the ratios of CD8, CD4, and CD1 positive thymic lymphocytes with aging significant increases in the ratios of HLA DR and CD20 positive cells, and no significant change in the ratio of CD3 positive cells. Immunohistological staining indicated a predominance of CD8, CD4, and CD1 positive cells in the cortex of the thymus, while a predominance of CD3, HLA-DR, and CD20 positive cells was indicated in the medulla of the thymus. The mitogen responses of thymic lymphocytes to PHA, Con A, and PWM were enhanced with aging. Quantitative analysis of the subsets of thymic lymphocytes, their distribution in the thymus, and the measurement of the mitogen responsiveness of those lymphocytes are indispensable for obtaining basic data indicating immunological changes of the thymus with aging, as well as for clarifying the age related characteristics of thymic lymphocytes in cases of autoimmune diseases such as myasthenia gravis. PMID- 1508141 TI - [Surgical treatment of chronic intestinal ischemia associated with combined valvular disease]. AB - A 69-year-old male was admitted with congestive heart failure and postprandial abdominal pain with weight loss. Combined valvular disease (MR III+TR III) was demonstrated by cardiac catheterization. Selective visceral arteriography revealed 75% stenosis at the origin of SMA and common hepatic artery arose beyond the stenosis. SMA-abdominal aortic bypass grafting using auto-saphenous vein graft was performed initially. Postprandial abdominal pain disappeared after bypass grafting, and then MVR with Bjork-Shiley mechanical valve and TAP with Carpentier- Edwards ring was performed. PMID- 1508142 TI - [Analysis of proliferative activities on parathyroid tumors using Ag-NORs (nucleolar organizer regions) staining and flow cytometry: preliminary report]. PMID- 1508143 TI - [Immunological competence and effect of PSK in patients with gastric cancer and colon cancer: preliminary report]. PMID- 1508144 TI - [Effect of lipid A on the production of tumor necrosis factor (TNF) and antitumor activity against pancreatic cancer cells: preliminary report]. PMID- 1508145 TI - Genetic and molecular evidence for a trans-acting regulatory locus controlling glutathione S-transferase-2 expression in Aedes aegypti. AB - The amount of glutathione S-transferase-2 (GST-2) protein and enzyme activity in a mutant strain (strain GG) of the yellow fever mosquito (Aedes aegypti) is approximately 25-fold higher than in the wild-type (++) strain. The mode of inheritance of the GG phenotype was studied in F1 and backcross progeny using GST enzyme assays, isozyme-specific antisera, and Northern blot analysis. Enzyme assay of parental and F1 progeny showed that the ++ phenotype was dominant to the GG phenotype. This was true for larvae as well as for all tissues examined in adults in both sexes. Immunoblotting experiments showed that, like the ++ strain, F1 larvae and adults express very low levels of GST-2 protein compared with the GG strain. Northern blotting experiments showed that the steady-state levels of GST-2 mRNA in parental and F1 hybrid larvae closely matched the enzyme activity and immunological data. These results suggest the existence of a trans-acting regulatory locus that acts to repress GST-2 mRNA transcription and/or decrease GST-2 mRNA stability in ++ and F1 hybrids. GST enzyme activity in backcross progeny, however, did not segregate into the two distinct phenotypes (low and high) predicted for a single locus, dominant allele model. Backcross progeny expressed a wide range of GST activity and GST-2 protein amount with no apparent fit to simple Mendelian ratios. These backcross data suggest that additional loci are also involved in regulating GST-2 isozyme expression.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1508146 TI - Use of the polymerase chain reaction to isolate an S-locus glycoprotein cDNA introgressed from Brassica campestris into B. napus ssp. oleifera. AB - A self-incompatible canola-quality Brassica napus ssp. oleifera line (W1) was generated by introgressing the S-locus from a self-incompatible B. campestris plant into the Westar cultivar. Using the polymerase chain reaction (PCR) with primers derived from conserved regions in S-locus glycoprotein (SLG) alleles, the central region of the active SLG gene (910) was obtained. The remaining portions of the cDNA for this 910 gene were subsequently cloned using the PCR-rapid amplification of cDNA ends (RACE) procedure. Sequence analysis revealed that the 910 cDNA show a high degree of sequence similarity to SLG alleles associated with Class I self-incompatible lines. The 910 gene was found to be absent in the original self-compatible cv. Westar (B. napus) and segregated with self incompatibility in a mixed population generated from a cross between self incompatible W1 and self-compatible Westar. RNA blot analysis indicated that high levels of 910 mRNAs were present in the stigma as buds approached anthesis. Thus, the SLG allele of W1 transferred from B. campestris via backcrosses to a line of cv. Westar has been identified. PMID- 1508147 TI - ore2, a mutation affecting proline biosynthesis in the yeast Saccharomyces cerevisiae, leads to a cdc phenotype. AB - We report here the isolation of temperature-sensitive mutants of the yeast Saccharomyces cerevisiae which exhibit cdc phenotypes. The recessive mutations defined four complementation groups, named ore1, ore2, ore3 and ore4. At the non permissive temperature, strains bearing these mutations arrested in the G1 phase of the cell cycle. The wild-type allele of the gene altered in ore2 mutants was cloned. The nucleotide sequence of a fragment which can complement the mutation showed the presence of an open reading frame capable of encoding a protein with 286 amino acid residues. The deduced amino acid sequence showed 25% identity with that of the Escherichia coli delta 1-pyrroline-5-carboxylate reductase, an enzyme of the pathway for the biosynthesis of proline. The ore2 mutants, correspondingly, were found to be capable of growing at the non-permissive temperature on a synthetic medium supplemented with proline. In addition, the chromosomal location of the gene and its restriction map were compatible with those previously reported for the PRO3 gene which encodes the S. cerevisiae delta 1-pyrroline-5-carboxylate reductase. PMID- 1508148 TI - Stress response induced by DNA damage leads to specific, delayed and untargeted mutations. AB - Cells of the mouse T-lymphoma line GRSL13 were treated with 8-methoxy-psoralen plus longwave ultraviolet light (PUVA) under conditions where the biological effects are mainly due to non-persistent DNA cross-links (PUVA-CL treatment). Fluctuation analysis showed that PUVA-CL treatment resulted in an enhancement of the mutation rate in the progeny of treated cells, which persisted until the eleventh generation after treatment. Since only 5 cross-links are available to account for 52 mutational events observed in the coding region, about 90% of the induced mutational events must have been untargeted. This was confirmed by molecular analysis of these mutations, which showed that 53% of the point mutations arose at sites which are not a target for psoralens. This supports the hypothesis that stress responses may give rise to untargeted mutagenesis. Further support for this hypothesis is provided by the observation that 8-methoxy psoralen (8-MOP) or UVA alone (both of which are known to induce many pleiotropic effects) each acted as indirect mutagen by enhancing the mutation rate 2-4 fold in the progeny of treated cells. PMID- 1508150 TI - Molecular characterization of two types of 22 kilodalton alpha-zein genes in a gene cluster in maize. AB - Five genes of the alpha-zein subfamily four (SF4) are located in a 56 kb genomic region of the maize inbred line W22. Their nucleotide and deduced amino acid sequences have been determined. The sequences define two types of alpha-zein SF4 genes-type 1 (T1) and type 2 (T2). The single T1 alpha-zein SF4 gene codes for an alpha-zein protein with a M(r) of about 22,000. This is the first alpha-zein SF4 gene sequenced that contains no early in-frame stop codons in its coding sequence. The four T2 alpha-zein SF4 genes in this cluster contain one or two early in-frame stop codons. In addition, our T1 and T2 genes differ markedly in the base sequences of their distal 5' non-translated flanking regions. The nucleotide and the deduced amino acid sequences of these two types of alpha-zein SF4 genes are similar (greater than 90%) to one another and to all known alpha zein SF4 genes and cDNAs. Of the known W22 alpha-zein SF4 genes, only one in six does not contain an early in-frame stop codon. If the number of alpha-zein SF4 genes is 15-20, then we estimate that only about 4 of the W22 alpha-zein SF4 genes are without in-frame early stop codons. PMID- 1508149 TI - Structure and regulation of yeast HEM3, the gene for porphobilinogen deaminase. AB - Porphobilinogen deaminase is the third enzyme in the heme biosynthetic pathway. hem3 mutants in Saccharomyces cerevisiae are deficient in porphobilinogen deaminase activity. We have isolated the HEM3 gene by complementation of the heme auxotrophy of a hem3 mutant. Sequence analysis reveals an open reading frame of 981 nucleotides. The derived amino acid sequence of the protein encoded by HEM3 shows extensive homology to the reported sequences for porphobilinogen deaminase from a number of other sources, indicating that HEM3 is the structural gene for porphobilinogen deaminase. Earlier reports have suggested that expression of HEM3 is induced by porphobilinogen, the substrate of the encoded enzyme. We have investigated the transcription of HEM3 and have found that it is not affected by the ability of the cell to make porphobilinogen or heme. However, we have found that HAP2 and HAP3 gene products are involved in the expression of HEM3. An important element required for expression of HEM3 has been localized to a small region that contains a sequence homologous to the HAP2-3-4 binding sites of several genes including HEM1. These findings suggest that HEM3 expression is regulated in the same manner as that of HEM1 which encodes the first enzyme of the heme biosynthetic pathway. PMID- 1508151 TI - Characterisation of actI-homologous DNA encoding polyketide synthase genes from the monensin producer Streptomyces cinnamonensis. AB - Cloned DNA encoding polyketide synthase (PKS) genes from one Streptomyces species was previously shown to serve as a useful hybridisation probe for the isolation of other PKS gene clusters from the same or different species. In this work, the actI and actIII genes, encoding components of the actinorhodin PKS of Streptomyces coelicolor, were used to identify and clone a region of homologous DNA from the monensin-producing organism S. cinnamonensis. A 4799 bp fragment containing the S. cinnamonensis act-homologous DNA was sequenced. Five open reading frames (ORFs 1-5) were identified on one strand of this DNA. The five ORFs show high sequence similarities to ORFs that were previously identified in the granaticin, actinorhodin, tetracenomycin and whiE PKS gene clusters. This allowed the assignment of the following putative functions to these five ORFS: a heterodimeric beta-ketoacyl synthase (ORF1 and ORF2), an acyl carrier protein (ORF3), a beta-ketoacyl reductase (ORF5), and a bifunctional cyclase/dehydrase (ORF4). The ORFs are encoded in the order ORF1-ORF2-ORF3-ORF5-ORF4, and ORFs-1 and -2 show evidence for translational coupling. This act-homologous region therefore appears to encode a PKS gene cluster. A gene disruption experiment using the vector pGM160, and other evidence, suggests that this cluster is not essential for monensin biosynthesis but rather is involved in the biosynthesis of a cryptic aromatic polyketide in S. cinnamonensis. An efficient plasmid transformation system for S. cinnamonensis has been established, using the multicopy plasmids pWOR120 and pWOR125. PMID- 1508152 TI - Homologous genes for the C4 isoform of phosphoenolpyruvate carboxylase in a C3 and a C4 Flaveria species. AB - The C4 isoform of phosphoenolpyruvate carboxylase (PEPCase) in Flaveria trinervia is encoded by the ppcA subgroup of the PEPCase gene family and is abundantly expressed in the mesophyll cells of leaves. The homologous ppcA genes in the C3 plant F pringlei are only weakly expressed and their transcripts do not show the strictly leaf-specific accumulation pattern observed for the F. trinervia genes. Two representative members of the ppcA subfamilies of F. trinervia (C4) and F. pringeli (C3)-named ppcA1-were characterized by Southern blotting, nucleotide sequencing and primer extension analysis. Comparison of the deduced amino acid sequences reveals a close similarity between C4 and C3 isoforms. Only few C4 specific positions can be detected when all known plant PEPCases are included in the comparison. A regulatory domain involved in light-dependent phosphorylation/dephosphorylation of the C4 and crassulacean acid metabolism (CAM) isoforms is present in the ppcA1 gene products of both the C3 and C4 Flaveria. The 5' flanking regions are essentially homologous. The putative promoter regions share several identical sequence motifs (CCAAT, AT-1 and GT-1 box III/III* elements). Additionally, alterations in elements that could contribute to differences in expression rates and light regulation are found. The significance of these findings is discussed with respect to the molecular evolution of C4 photosynthesis in Flaveria. PMID- 1508153 TI - Organization and regulation of the Bacillus subtilis odhAB operon, which encodes two of the subenzymes of the 2-oxoglutarate dehydrogenase complex. AB - The primary structure of Bacillus subtilis 105 kDa 2-oxoglutarate dehydrogenase (E10) was deduced from the nucleotide sequence of the odhA gene and confirmed by N-terminal sequence analysis. The protein is highly homologous to E1o of Azotobacter vinelandii and Escherichia coli and of bakers' yeast cells. The 5' end of the odhAB mRNA was determined and the promoter region for the odhAB operon was localized to a 375 bp DNA fragment. The cellular concentration of the 4.5 kb odhAB transcript was found to be growth stage dependent; its concentration during growth in nutrient sporulation medium decreased abruptly at the end of the exponential growth phase and it was not detectable in early stationary phase. This decrease in the cellular concentration of the transcript is not the result of an increased rate of decay of the full-length odhAB mRNA, suggesting that transcription is down-regulated at the end of the exponential growth phase. The cellular concentration of the odhA and odhB gene products, E1o and dihydrolipoamide transsuccinylase (E2o), remains essentially constant throughout the growth curve in nutrient sporulation medium, indicating that both are rather stable proteins. In exponentially growing cells, glucose in nutrient sporulation medium repressed the cellular concentration of the odhAB mRNA, as well as that of E1o and E2o, about four-fold. This effect is most likely the result of a decreased rate of transcription from the odhAB promoter, since neither the stability nor the 5'-end of the transcript were affected by glucose in the medium. It is concluded that the cellular concentration of the 2-oxoglutarate dehydrogenase multienzyme complex (E1o and E2o) is regulated mainly at the transcriptional level. PMID- 1508154 TI - Efficient transformation of Claviceps purpurea using pyrimidine auxotrophic mutants: cloning of the OMP decarboxylase gene. AB - A homologous transformation system was developed for the phytopathogenic fungus Claviceps purpurea. Orotidine-5'-monophosphate decarboxylase (OMPD)-deficient mutants were obtained by UV mutagenesis and selection for resistance against 5 fluoroorotate. These mutants could be complemented well by the corresponding genes of Aspergillus niger (pyrA) and Neurospora crassa (pyr4), yielding significantly higher transformation rates (and lower copy numbers per transformant) than the phleomycin resistance system. The homologous OMPD gene was isolated from a lambda genomic library by heterologous hybridization with the pyr4 gene of N. crassa, identified by complementation of Aspergillus and Claviceps mutants, and used to confirm homologous integration in Claviceps. The pyr transformation system also proved to be very efficient in cotransformation experiments using the bacterial beta-glucuronidase gene (uidA) as a reporter gene, which was also efficiently expressed during the parasitic cycle: honeydew produced by plants infected with pyr/uidA cotransformants was shown to contain significant levels of beta-glucuronidase activity. PMID- 1508155 TI - Asymmetric somatic cell hybridization in plants. I. The early effects of (sub)lethal doses of UV and gamma radiation on the cell physiology and DNA integrity of cultured sugarbeet (Beta vulgaris L.) protoplasts. AB - An investigation into the possible application of UV radiation as a pretreatment for the donor cells in asymmetric plant cell hybridization protocols has been carried out. A comparison was made between the effects of UV doses in the range 700-4200 J/m2 and those of 60Co gamma radiation over the range 0.15-1 kGy on Beta vulgaris suspension cell protoplasts. The investigation had two aspects. Firstly, alterations to cell physiology (cell wall resynthesis, viability, division and colony formation) in irradiated protoplasts were examined during a 4-week culture period. Results have indicated that a dose of 700 J/m2 UV is necessary to prevent further cell division and colony formation in these cells. A dose of 0.15 kGy gamma radiation generally prevented colony formation, although some early cell division did occur (as was also observed even after 0.45 kGy had been applied). Membrane integrity, as measured after 6 days, using fluorescein diacetate staining, was not affected by either treatment within the dose ranges applied. Secondly, denaturing (alkaline) gel electrophoresis, in association with a pulsed field gel DNA preparation technique, was used to determine the degree of in vivo DNA damage following the radiation treatments. After UV radiation, considerable fragmentation of the DNA was observed, the extent of which was dose-dependent. Gamma radiation, however, appeared to result in fewer DNA lesions, with only the 1 kGy treatment revealing a pattern significantly altered from that of the control. These results augur well for the potential use of UV radiation in asymmetric fusion experiments. PMID- 1508156 TI - Asymmetric somatic cell hybridization in plants. II. Electrophoretic analysis of radiation-induced DNA damage and repair following the exposure of sugarbeet (Beta vulgaris L.) protoplasts to UV and gamma rays. AB - As part of an investigation into whether it would be possible to use UV radiation as a suitable pretreatment of the donor cells in asymmetric hybridization experiments, the effects of this treatment on sugarbeet (Beta vulgaris L.) protoplast DNA have been determined and compared with those of gamma radiation. Both nuclear and mitochondrial DNAs have been examined. The dose ranges chosen had previously been determined to be potentially applicable for fusion experiments. Pulsed field gel electrophoresis and standard agarose gel electrophoresis have been used in combination with laser scanning densitometry to gain an insight into the precise nature and degree of DNA damage resulting from irradiation. It was observed that UV radiation introduced substantial modifications to sugarbeet DNA. Double-strand breaks were detected, the number of which was found to be directly proportional to the dose applied. Such breaks indicate that UV radiation results in substantial chromosome/chromatid fragmentation in these cells. Chemical modifications to the DNA structure could be revealed by a significant reduction in DNA hybridization to specific mitochondrial and nuclear DNA probes. Following gamma irradiation at equivalent biological doses (i.e. those just sufficient to prevent colony formation) much less damage was detected. Fewer DNA fragments were produced indicating the presence of fewer double-strand breaks in the DNA structure. In comparison to UV treatments, DNA hybridization to specific probes following gamma radiation was inhibited less. For both treatments, mitochondrial DNA appeared more sensitive to damage than nuclear DNA. The possibility that DNA repair processes might account for these differences has also been investigated. Results indicate either that repair processes are not involved in the effects observed or that DNA repair occurs so fast that it was not possible to demonstrate such involvement with the experimental system used. The general relevance of such processes to asymmetric cell hybridization is discussed. PMID- 1508157 TI - Cloning and nucleotide sequence of the ptsG gene of Bacillus subtilis. AB - The ptsG gene of Bacillus subtilis encodes Enzyme IIGlc of the phosphoenolpyruvate: glucose phosphotransferase system. The 3' end of the gene was previously cloned and the encoded polypeptide found to resemble the Enzymes IIIGlc of Escherichia coli and Salmonella typhimurium. We report here cloning of the complete ptsG gene of B. subtilis and determination of the nucleotide sequence of the 5' end. These results, combined with the sequence of the 3' end of the gene, revealed that ptsG encodes a protein consisting of 699 amino acids and which is similar to other Enzymes II. The N-terminal domain contains two small additional fragments, which share no similarities with the closely related Enzymes IIGlc and IINag of E. coli but which are present in the IIGlc-like protein encoded by the E. coli malX gene. PMID- 1508158 TI - Isolation and characterization of mutants of Aspergillus niger deficient in extracellular proteases. AB - In the present study, the extracellular protease activity in a strain of the filamentous fungus Aspergillus niger was investigated and mutant strains deficient in the production of extracellular proteases were isolated. The major protease, which is responsible for 80-85% of the total activity, is aspergillopepsin A, a protein of ca. 43 kDa, the activity of which is inhibited by pepstatin. In addition, a second protease, aspergillopepsin B, is produced, which is much less sensitive to inhibition by pepstatin. Several protease deficient mutants were obtained by in vivo UV mutagenesis. In addition, a mutant lacking aspergillopepsin A was constructed by an in vitro gene replacement strategy. In this mutant, AB1.1, the entire coding region of the gene for aspergillopepsin A (pepA) is deleted. In three UV-induced mutants, aspergillopepsin A is also missing. One of these mutants, AB1.18, is mutated in the pepA gene, which is located on chromosome I. One of the other mutants, AB1.13, which has only 1-2% of the extracellular protease activity in the parent strain, is deficient in both aspergillopepsin A and aspergillopepsin B. The mutation involved, prt-13, has been localized to chromosome VI, and is probably a mutation in a regulatory gene. Another mutation involved in loss of protease function, prt-39, is located on chromosome VIII. Degradation of various heterologous proteins in culture media of the mutants is reduced but, even in strain AB1.13, not completely abolished. PMID- 1508159 TI - The role of autoantigens in the induction and maintenance of autoimmunity. PMID- 1508160 TI - Use of synthetic peptides for the detection and quantification of autoantibodies. AB - The rapid progress made over the last 10 years in the identification of individual autoantigens and in the localization of the epitopes involved, has resulted in a parallel reduction in the complexity of the antigen required for the detection of autoantibodies. The ability to use synthetic peptides as antigens is a remarkable culmination of this process considering that many antigenic particles contain multiple proteins (eg. Sm consist of 8 or more individual proteins). Despite the fact that patients with SLE have a polyclonal hypergammaglobulinemia, excellent correlations between ELISAs utilizing the P2 or SmB/B' synthetic peptides, ELISAs utilizing r proteins and immunoblotting were obtained [28, 38, 50]. However, false positive/non-specific binding to a P2-BSA glutaraldehyde conjugate has been observed with serum from old MRL/lpr mice (unpublished observations). In addition, some of the results obtained in human autoimmune diseases suggest that non-specific binding may be problematic in some instances. It is difficult, at present, to know whether the higher frequencies of detection of autoantibodies to certain synthetic peptide antigens reflect increased sensitivity or decreased specificity. Synthetic peptide antigens have been used to detect autoantibodies in both organ specific and multisystem autoimmune diseases. In only a small number of cases have these reagents been rigorously tested for sensitivity and specificity. Despite this, synthetic peptides have been shown to be valuable for detection and quantification of autoantibodies in certain clinical situations. Undoubtedly, further progress in epitope mapping of autoantigens coupled with technological advances in protein synthesis and improved prediction of protein structure will lead to a large number of synthetic peptide antigens for research and clinical applications.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1508161 TI - [Elongation factor EF-Ts interacts with the aminoacyl-tRNA.EF-Tu.GTP complex]. AB - The fluorescence polarization technique has been used to study the interaction of the EF-Ts dansyl derivative with EF-Tu after nucleotide exchange and binding of the aminoacyl-tRNA to EF-Tu.GTP. It is shown that the ternary complex formation results in the increase of EF-Ts affinity to EF-Tu and EF-Ts remains bound to EF Tu up to the GTP hydrolysis stage on the ribosome. PMID- 1508162 TI - [Synthesis of a bovine adrenodoxin precursor in vitro and its import into yeast mitochondria]. AB - The bovine adrenal cortex adrenodoxin gene was inserted into pTZ19 under T7 promoter control. The adrenodoxin mRNA was synthesized with T7 RNA polymerase and then translated in the reticulocyte cell-free translation system. The protein product was identified as the adrenodoxin precursor with molecular weight 22000. The import of the precursor into isolated yeast mitochondria was carried out. The protein was found to be inserted into the trypsin-insensitive compartment of mitochondria via an energy dependent way. This resulted in the processing of the precursor to the 12000-mature form. Thus, the precursor of mammalian adrenodoxin can be normally imported into yeast mitochondria. PMID- 1508163 TI - [Identification of the gene for the immunodominant p35 protein from vaccinia virus]. AB - A major immunodominant envelope protein p35 of vaccina virus was purified by means of extraction from virions with detergent NP-40. The protein was cleaved with CNBr, four homogenous peptides were isolated and their N-terminal amino acid sequences were determined. Computer search in a protein sequences data bank revealed that the immunodominant protein p35 of vaccinia virus is encoded by H3 gene in HindIII-H fragment of vaccinia virus genome. PMID- 1508164 TI - [Calorimetric study of the thermal denaturation of beta-lactoglobulin in the presence of urea and phosphate ions]. AB - The denaturation of beta-lactoglobulin in solution with different content of urea and phosphates has been studied calorimetrically. It has been shown that the increase of phosphate ion concentration in solution leads to an increase of beta lactoglobulin stability, while increase of urea concentration leads to an opposite effect. The variation of these components in solution practically does not influence the value of the heat capacity increment of beta-lactoglobulin in the considered temperature region. Accordingly the denaturation enthalpy is a linear function of temperature whose slope does not differ for solution with urea concentration less than 4.4 M. However, the absolute value of denaturation enthalpy in these solutions at corresponding temperatures differs significantly due to the heat effect of additional urea solvation during transition to the denatured state. The latter leads to a decrease of the overall denaturation enthalpy and, as a result, a shift of the enthalpy plot to higher temperatures providing conditions for studying the thermodynamic and structural characteristics of the molecule in the cold denatured-state. PMID- 1508165 TI - [Expression of the gene for tick-borne viral encephalitis virus NS3 protein in Escherichia coli cells]. AB - On the base of two overlapping cDNA-clones of tick-borne encephalitis virus (TBEV) genome and synthetic DNA fragments full DNA-copy of the TBEV NS3 protein gene was constructed and expressed in the E. coli cells. It was demonstrated that the relatively low biosynthesis level of full-length NS3 protein in the bacteria was due to the toxicity of the N-terminal region of the protein, consisting of it's first 180 amino acid residues. A form of the gene with deletion of nucleotides coding for the toxic region (called NS3*) was constructed and effective bacterial product of NS3* protein was obtained. The panel of monoclonal antibodies to TBEV NS1 and NS3 proteins was generated. According to the results of experiments of the binding of the monoclonal antibodies 18B2 to the bacterial products of NS3 and NS3* genes it was concluded, that the antigenic determinant recognized by these antibodies was located between 174 and 236 amino acids of TBEV NS3 protein. PMID- 1508166 TI - [Study of the structure of human serum albumin, liberated from fatty acids, by a tritium marker method]. AB - To elucidate the natural fatty acids effect on the human serum albumin (HSA) structure a new method of tritium labelling was used. The main peculiarity of the method consists in the possibility to get information on the qualitative and quantitative amino acid composition of the surface layer of the protein globule at different conformational states of the globule. Defatted HSA was shown to be characterized a higher accessibility of Asx, Glx, Thr, Ser, Gly, Pro, Ile, Tyr residues while the other residues remain unchanged. Asx residues are characterized by the largest changes (about 8 folds). Full accessible protein surface during defatting increases from 39,000 to 48,000 A2. Fatty acids connected with albumin in the relation 1-3 moles/mol of protein are noted to be the factor increasing the globule compactness and stipulating for the conformational protein stability to warmth, urine and guanidine salts effect. PMID- 1508167 TI - [Nucleotide sequence of the pNB2 plasmid from thermophilic bacteria Clostridium thermosaccharolyticum]. AB - The complete nucleotide sequence of pNB2, a 1.9-kilobases cryptic plasmid from thermophilic Clostridium thermosaccharolyticum has been determined. The plasmid consists of 1882 base pairs and has a G+C composition of 27.2%. The sequence contains three open reading frames capable of coding for polypeptides two of which were identified in maxicell Escherichia coli extracts. Our future studies are directed toward a construction of pNB2-derivatives as vectors for Clostridia. PMID- 1508168 TI - [Introduction of statistical mutations into strictly defined areas of the genome using a modified oligonucleotide]. AB - A method for inducing mutations in the short region of a gene is suggested. The method involves oligonucleotide modification by hydroxylamine derivative, in vitro enzymatic synthesis of double-stranded DNA using modified oligonucleotide as a primer and selection of mutant colonies using the starting unmodified oligonucleotide as a probe. PMID- 1508169 TI - [Analogs of nucleotides, modified by a sugar residue and pyrimidine base, in a DNA synthesis reaction, catalyzed by Thermus aquaticus DNA polymerase]. AB - Substrate properties of dNTP analogues in the DNA synthesis reaction catalyzed by Thermus aquaticus DNA polymerase were studied. It was shown that most of dNTP analogues which were known as terminators of DNA synthesis of E. coli DNA polymerase I were able to terminate DNA synthesis catalyzed by Thermus aquaticus DNA polymerase. An interesting feature of Thermus aquaticus DNA polymerase was the ability to utilize 3'-azido-2',3'-dideoxythymidine triphosphate as terminating substrate. Relative efficiency of tested dNTP analogues incorporation into the DNA growing chain was estimated. PMID- 1508170 TI - [Inhibition of reproduction of the human immunodeficiency virus in cell culture by 2',3'-dideoxynucleoside-5'-phosphites]. AB - 5'-Phosphites (5'-hydrogenphosphonates) of 2',3'-dideoxynucleosides (T, A, G, C) were synthesized and studied as inhibitors of human immunodeficiency virus type 1 (HIV-1) in MT4 and CEM13 cell cultures. It was shown that all 5'-phosphites effectively inhibit the production of viral antigens and protect cells from the cytotoxic effect of HIV infection. 5'-Phosphites were more active antiviral compounds than the corresponding nucleosides. PMID- 1508171 TI - [Expression of human urokinase in inoculated rodent cells. Loss of introns during gene transfer using a retroviral vector]. AB - Expression of urokinase in murine and rat cells was performed by two recombinant constructs, one containing cDNA and the other--hybrid (cDNA/genome) variant of human urokinase gene conserving 7 introns of 10, in the eukaryotic retrovirus vector pPS-3-neo. DNA of both constructs was introduced into packaging cell line psi 2 by a standard Ca-phosphate transfection technique. Infection of mouse and rat fibroblasts BALB/c 3T3 and Rat I with virus particles, produced by transfected psi 2 cells, led to an integration into the host genome of one or two recombinant proviral copies. Stable expression and secretion into the culture medium of glycosylated high molecular weight human urokinase was observed for both cell types. For the hybrid gene construct, precise excision of intervening sequences was shown during transferring of genetic material from packaging to recipient cells. PMID- 1508172 TI - [Single-stranded DNA from viruses, prokaryotes and eukaryotes]. AB - The review presents the results of investigations of single-stranded DNAs of viruses, bacteria and cells of higher organisms. Methods of revealing, isolating and analysis of these DNAs are presented. A large variety of single-stranded DNA containing genomes of plant and animal viruses was revealed. Attention is drawn to the integration and replication of viral genomes. Results of SV40 integration during the first two days after infection of Chinese hamster cells are shown. Results of studying multi-copy single-stranded DNA in bacterial cells were analysed. In separate sections, the replication of plasmid single-stranded DNA was studied as well as the problem of plasmid stability in cells. Advances in bacteria transformation studies are stated. Data of single-stranded DNA investigation in cells of higher organisms are mainly presented on the example of early embryos. Data on the analysis of gene hypersensitivity to nuclease S1 are given. A table of proteins destabilizing and unweaving single-stranded DNA and a classification table of proteins bound with single-stranded DNA according to their functional significance are presented. It is stated that the problem of single-stranded DNA significance in cells remains open, although some results have been achieved. PMID- 1508173 TI - [Immunoelectron-microscopic determination of the localization of tryptophanyl tRNA synthetase in eubacterial cells of Escherichia coli and Methanococcus halophilus archaebacteria]. AB - Localization of tryptophanyl-tRNA-synthetase (TRS) was studied in halophilic archaebacterium Methanococcus halophilus and eubacterium E. coli. Ultrathin sections of the cells, fixed with glutaraldehyde and embedded in "Lowicryl K4M" at -35 degrees C, were treated with colloidal gold complexes containing monoclonal antibodies Aml against TRS. The latter bind specifically to TRS isolated both from eucaryotes, archae- and eubacteria. According to the label distribution three zones in M. halophilus and E. coli can be distinguished: (i) about 75% of the whole amount of gold particles are localized in the cytoplasm, the distribution of label being more or less homogeneous; (ii) cytoplasmic regions, adjacent to nucleoid, are intensively labelled (about 20% of the whole amount of label); (iii) very few gold particles (not more than 10% of the whole amount) are present in the nucleoid. The data obtained show, that the distribution of TRS in the nucleoid and cytoplasm of archaebacterium M. halophilus is close to the distribution of TRS, found in E. coli. It supports our previous conclusion that the structural organization of transcription-translation apparatus in methanogen and halophilic archaebacteria is similar to that in eubacteria. PMID- 1508174 TI - ["DIROM"--an interactive system for planning experiments on directed mutagenesis and design of artificial genes]. AB - We present a computer system "DIROM" for oligonucleotide-directed mutagenesis and artificial gene design experiments planning and support. "DIROM" allows to search for optimal oligonucleotides according to such parameters as sufficient energy of oligonucleotide-target hybridization, secondary structure of oligonucleotide and target DNA, presence of alternative attachment sites in target DNA, terminal G/C pairs presence. Both single-stranded and double-stranded vector mutagenesis methods are implemented. It can be also used for optimal primer selection for polymerase chain reaction, sequencing etc. "DIROM" can search for both existent and potential carry out vector+target sequence construction. Both amino acid and nucleotide sequences can be operated. PMID- 1508175 TI - COT1, a gene involved in cobalt accumulation in Saccharomyces cerevisiae. AB - The COT1 gene of Saccharomyces cerevisiae has been isolated as a dosage-dependent suppressor of cobalt toxicity. Overexpression of the COT1 gene confers increased tolerance to cobalt and rhodium ions but not other divalent cations. Strains containing null alleles of COT1 are viable yet more sensitive to cobalt than are wild-type strains. Transcription of COT1 responds minimally to the extracellular cobalt concentration. Addition of cobalt ions to growth media results in a twofold increase in COT1 mRNA abundance. The gene encodes a 48-kDa protein which is found in mitochondrial membrane fractions of cells. The protein contains six possible membrane-spanning domains and several potential metal-binding amino acid residues. The COT1 protein shares 60% identity with the ZRC1 gene product, which confers resistance to zinc and cadmium ions. Cobalt transport studies indicate that the COT1 product is involved in the uptake of cobalt ions yet is not solely responsible for it. The increased tolerance of strains containing multiple copies of the COT1 gene is probably due to increased compartmentalization or sequestration of the ion within mitochondria. PMID- 1508177 TI - Meiotic induction of the yeast HOP1 gene is controlled by positive and negative regulatory sites. AB - The process of meiosis and sporulation in the yeast Saccharomyces cerevisiae is a highly regulated developmental pathway dependent on genetic as well as nutritional signals. The HOP1 gene, which encodes a component of meiotic chromosomes, is not expressed in mitotically growing cells, but its transcription is induced shortly after yeast cells enter the meiotic pathway. Through a series of deletions and mutations in the HOP1 promoter, we located two regulatory sites that are essential for proper regulation of HOP1. One site, called URS1H, brings about repression of HOP1 in mitotic cells and functions as an activator sequence in cells undergoing meiosis. The second site, which we designated UASH, acts as an activator sequence in meiotic cells and has similarity to the binding site of the mammalian CCAAT/enhancer binding protein (C/EBP). Both sites are required for full meiotic induction of the HOP1 promoter. We conclude that in mitotic yeast cells, the URS1H site maintains the repressed state of the HOP1 promoter, masking the effect of the UASH site. Upon entry into meiosis, repression is lifted, allowing the URS1H and UASH sites to activate high-level transcription. PMID- 1508176 TI - Elements upstream of the AAUAAA within the human immunodeficiency virus polyadenylation signal are required for efficient polyadenylation in vitro. AB - Recent in vivo studies have identified specific sequences between 56 and 93 nucleotides upstream of a polyadenylation [poly(A)] consensus sequence, AAUAAA, in human immunodeficiency virus type 1 (HIV-1) that affect the efficiency of 3' end processing at this site (A. Valsamakis, S. Zeichner, S. Carswell, and J. C. Alwine, Proc. Natl. Acad. Sci. USA 88:2108-2112, 1991). We have used HeLa cell nuclear extracts and precursor RNAs bearing the HIV-1 poly(A) signal to study the role of upstream sequences in vitro. Precursor RNAs containing the HIV-1 AAUAAA and necessary upstream (U3 region) and downstream (U5 region) sequences directed accurate cleavage and polyadenylation in vitro. The in vitro requirement for upstream sequences was demonstrated by using deletion and linker substitution mutations. The data showed that sequences between 56 and 93 nucleotides upstream of AAUAAA, which were required for efficient polyadenylation in vivo, were also required for efficient cleavage and polyadenylation in vitro. This is the first demonstration of the function of upstream sequences in vitro. Previous in vivo studies suggested that efficient polyadenylation at the HIV-1 poly(A) signal requires a spacing of at least 250 nucleotides between the 5' cap site and the AAUAAA. Our in vitro analyses indicated that a precursor containing the defined upstream and downstream sequences was efficiently cleaved at the polyadenylation site when the distance between the 5' cap and the AAUAAA was reduced to at least 140 nucleotides, which is less than the distance predicted from in vivo studies. This cleavage was dependent on the presence of the upstream element. PMID- 1508178 TI - Initiation of DNA replication in the dihydrofolate reductase locus is confined to the early S period in CHO cells synchronized with the plant amino acid mimosine. AB - In previous studies, we used two complementary two-dimensional gel electrophoretic methods to examine replication intermediates in the 240-kb amplified dihydrofolate reductase (DHFR) domain of methotrexate-resistant CHOC 400 cells (J. P. Vaughn, P. A. Dijkwel, and J. L. Hamlin, Cell 61:1075-1087, 1990). Surprisingly, in both asynchronous and early-S-phase cultures, initiation bubbles were detected in several contiguous fragments from a previously defined 28-kb initiation locus. However, because of the low levels of bubblelike structures observed on gels, it has been suggested that these structures might represent artifacts, possibly unrelated to replication per se. In this study, we have achieved much more synchronous entry into S phase by using a novel inhibitor and have isolated replication intermediates by a new procedure that largely eliminates branch migration and shear. Under these conditions, we find that (i) the relative number of bubblelike structures detected in fragments from the initiation locus is markedly increased, (ii) bubbles are detected at multiple sites scattered throughout the region lying between the DHFR and 2BE2121 genes, and (iii) bubbles appear and disappear in this region with the kinetics expected of an early-firing origin. These data strengthen the proposal that in vivo, initiation can occur at any of a large number of sites scattered throughout a broad zone in the DHFR domain. PMID- 1508179 TI - 95-kilodalton B-Raf serine/threonine kinase: identification of the protein and its major autophosphorylation site. AB - B-Raf, a member of the Raf family of serine/threonine kinases, is expressed primarily in the brain and in the nervous system. In this study, the biochemical properties of the B-Raf protein were investigated in nerve growth factor (NGF) responsive cell lines and in brain tissues. B-Raf was identified by using phosphopeptide mapping analysis and cDNA analysis as a 95-kDa protein which is primarily localized in the cytosol. NGF rapidly stimulated both serine and threonine phosphorylation in vivo and autophosphorylation activity in vitro of the B-Raf protein. In PC12 cells, B-Raf autokinase activity was induced by both differentiation factors and mitogens, with maximal activity observed after 5 min of factor addition. B-Raf kinase activity was also observed following NGF treatment of SH-SY5Y neuroblastoma cells and in adult mouse brain and hippocampus. Induction of B-Raf kinase activity in NGF-treated PC12 cells required expression of kinase-active trk receptors. Exogenous substrates or a peptide containing the autophosphorylation site became phosphorylated when added to immune complex kinase assays and reduced the in vitro autophosphorylation activity of B-Raf, suggesting that in vitro autophosphorylation sites and exogenous substrates compete for active sites of the B-Raf kinase. Finally, the major in vitro autophosphorylation site of B-Raf was identified as threonine 372 in the conserved region 2 domain. A threonine residue is present at similar positions in all three mammalian Raf family members and may represent a regulatory site for these proteins. PMID- 1508180 TI - Isolation of rsp-1, a novel cDNA capable of suppressing v-Ras transformation. AB - Using an expression cloning assay, we have isolated a novel cDNA, referred to as rsp-1, which suppresses the v-Ras-transformed phenotype. When introduced into NIH 3T3 fibroblasts under the control of a metallothionein promoter, rsp-1 confers resistance to v-Ras, but not to v-Mos or v-Src, and inhibits growth of the cells. The rsp-1 cDNA contains a 831-bp open reading frame encoding a 277-amino-acid leucine-rich protein. The rsp-1 cDNA exhibits no significant homology to sequences in the DNA data bases. However, searches of the protein data bases revealed that it contains a series of leucine-based repeats which are homologous to the leucine repeats found in the regulatory region of the yeast adenylyl cyclase. rsp-1 specific RNA is detectable in a wide variety of cell lines and tissues, and the gene is conserved among eukaryotic species. These data suggest that rsp-1 plays a role in Ras signal transduction. PMID- 1508181 TI - Functional analysis of box I mutations in yeast site-specific recombinases Flp and R: pairwise complementation with recombinase variants lacking the active-site tyrosine. AB - The site-specific recombinases Flp and R from Saccharomyces cerevisiae and Zygosaccharomyces rouxii, respectively, are related proteins that belong to the yeast family of site-specific recombinases. They share approximately 30% amino acid matches and exhibit a common reaction mechanism that appears to be conserved within the larger integrase family of site-specific recombinases. Two regions of the proteins, designated box I and box II, also harbor a significantly high degree of homology at the nucleotide sequence level. We have analyzed the properties of Flp and R variants carrying point mutations within the box I segment in substrate-binding, DNA cleavage, and full-site and half-site strand transfer reactions. All mutations abolish or seriously diminish recombinase function either at the substrate-binding step or at the catalytic steps of strand cleavage or strand transfer. Of particular interest are mutations of Arg-191 of Flp and R, residues which correspond to one of the two invariant arginine residues of the integrase family. These variant proteins bind substrate with affinities comparable to those of the corresponding wild-type recombinases. Among the binding-competent variants, only Flp(R191K) is capable of efficient substrate cleavage in a full recombination target. However, this protein does not cleave a half recombination site and fails to complete strand exchange in a full site. Strikingly, the Arg-191 mutants of Flp and R can be rescued in half-site strand transfer reactions by a second point mutant of the corresponding recombinase that lacks its active-site tyrosine (Tyr-343). Similarly, Flp and R variants of Cys 189 and Flp variants at Asp-194 and Asp-199 can also be complemented by the corresponding Tyr-343-to-phenylalanine recombinase mutant. PMID- 1508182 TI - Expression of a yeast metallothionein gene family is activated by a single metalloregulatory transcription factor. AB - The opportunistic pathogenic yeast Candida glabrata elicits at least two major responses in the presence of high environmental metal levels: transcriptional induction of the metallothionein gene family by copper and the appearance of small (gamma-Glu-Cys)nGly peptides in the presence of cadmium. On the basis of a trans-activation selection scheme in the baker's yeast Saccharomyces cerevisiae, we previously isolated a C. glabrata gene which encodes a copper-activated DNA binding protein designated AMT1. AMT1 forms multiple specific DNA-protein complexes with both C. glabrata MT-I and MT-IIa promoter DNA fragments. In this report, we localize and define the AMT1-binding sites in the MT-I and MT-IIa promoters and characterize the mode of AMT1 binding. Furthermore, we demonstrate that the AMT1 protein trans activates both the MT-I and MT-IIa genes in vivo in response to copper and that this activation is essential for high-level copper resistance in C. glabrata. Although AMT1-mediated trans activation of the C. glabrata metallothionein genes is essential for copper resistance, AMT1 is completely dispensable for cadmium tolerance. The distinct function that metallothionein genes have in copper but not cadmium detoxification in C. glabrata is in contrast to the role that metallothionein genes play in tolerance to multiple metals in higher organisms. PMID- 1508183 TI - Evidence for a role of protein kinase C zeta subspecies in maturation of Xenopus laevis oocytes. AB - A number of studies have demonstrated the activation of phospholipase C-mediated hydrolysis of phosphatidylcholine (PC-PLC) both by growth factors and by the product of the ras oncogene, p21ras. Evidence has been presented indicating that the stimulation of this phospholipid degradative pathway is sufficient to activate mitogenesis in fibroblasts as well as that it is sufficient and necessary for induction of maturation in Xenopus laevis oocytes. However, the mechanism whereby PC-PLC transduces mitogenic signals triggered by growth factors or oncogenes remains to be elucidated. In this study, data are presented that show the involvement of protein kinase C zeta subspecies in the channelling of the mitogenic signal activated by insulin-p21ras-PC-PLC in Xenopus oocytes as well as the lack of a critical role of protein kinase C isotypes alpha, beta, gamma, delta, and epsilon in these pathways. PMID- 1508184 TI - Characterization of the promoter region of the src family gene lyn and its trans activation by human T-cell leukemia virus type I-encoded p40tax. AB - The src family gene lyn is expressed preferentially in B lymphocytes but very little in normal T lymphocytes. Transcription of the lyn gene in T lymphocytes was shown to be induced by the p40tax protein encoded by human T-cell lymphotropic virus type I. For determination of the mechanism of p40tax-mediated trans activation, the transcriptional promoter region of the lyn gene was characterized. By endonuclease S1 mapping, the transcriptional initiation sites were identified within the 770-bp EcoRI-SacI fragment of the 5'-terminal portion of the human lyn gene. This fragment showed promoter activity when placed upstream of the bacterial chloramphenicol acetyltransferase gene and transfected into various cell lines. Nucleotide sequence analysis revealed that the lyn promoter region contained four GC box-like sequences but not a TATA or CCAAT box. In addition, it contained sequences characteristic of a cyclic AMP-responsive element, octamer-binding motif, PEA3-like motifs, and NF kappa B-binding motif like sequence. Mutational analysis suggested that the octamer-binding motif sequence is of primary importance for the lyn promoter activity but that the other elements are not. Cotransfection of various chloramphenicol acetyltransferase constructs containing different length of the lyn promoter together with p40tax expression plasmids into Jurkat T cells showed that the sequence responsible for p40tax-induced transcription is present around the transcription initiation sites. PMID- 1508185 TI - Transcription of the mouse secretory protease inhibitor p12 gene is activated by the developmentally regulated positive transcription factor Sp1. AB - We have previously shown that a trans-acting protein produced in some tissue culture cells positively control the transcriptional activity directed by the mouse p12 promoter. This nuclear protein exerts its positive activity by interacting with a regulatory sequence designated p12.A and located between the TATA and CCAAT box elements on the p12 gene promoter. Using DNase I and dimethyl sulfate methylation interference footprinting techniques coupled with gel retardation assays, we found evidence that the protein which binds to the p12.A element is the well-known transcription factor Sp1. Mutational analysis in transient transfection assays confirmed the positive activity exerted by this protein in every cell line tested. In agreement with this observation, we detected a p12.A-Sp1 binding activity in nuclear extracts prepared from all cell lines used. However, a similar binding activity could not be detected in a number of nuclear extracts prepared from normal mouse tissues. In this report, we provide the evidence that the lack of Sp1-binding activity results from the degradation of Sp1 in the kidney, liver, and pancreas of the mouse. PMID- 1508186 TI - Isolation of a gene required for programmed initiation of development by Aspergillus nidulans. AB - In contrast to many other cases in microbial development, Aspergillus nidulans conidiophore production initiates primarily as a programmed part of the life cycle rather than as a response to nutrient deprivation. Mutations in the acoD locus result in "fluffy" colonies that appear to grow faster than the wild type and proliferate as undifferentiated masses of vegetative cells. We show that unlike wild-type strains, acoD deletion mutants are unable to make conidiophores under optimal growth conditions but can be induced to conidiate when growth is nutritionally limited. The requirement for acoD in conidiophore development occurs prior to activation of brlA, a primary regulator of development. The acoD transcript is present both in vegetative hyphae prior to developmental induction and in developing cultures. However, the effects of acoD mutations are detectable only after developmental induction. We propose that acoD activity is primarily controlled at the posttranscriptional level and that it is required to direct developmentally specific changes that bring about growth inhibition and activation of brlA expression to result in conidiophore development. PMID- 1508187 TI - Role of GCR2 in transcriptional activation of yeast glycolytic genes. AB - The Saccharomyces cerevisiae GCR2 gene affects expression of most of the glycolytic genes. We report the nucleotide sequence of GCR2, which can potentially encode a 58,061-Da protein. There is a small cluster of asparagines near the center and a C-terminal region that would be highly charged but overall neutral. Fairly homologous regions were found between Gcr2 and Gcr1 proteins. To test potential interactions, the genetic method of S. Fields and O. Song (Nature [London] 340:245-246, 1989), which uses protein fusions of candidate gene products with, respectively, the N-terminal DNA-binding domain of Gal4 and the C terminal activation domain II, assessing restoration of Gal4 function, was used. In a delta gal4 delta gal80 strain, double transformation by plasmids containing, respectively, a Gal4 (transcription-activating region)/Gcr1 fusion and a Gal4 (DNA-binding domain)/Gcr2 fusion activated lacZ expression from an integrated GAL1/lacZ fusion, indicating reconstitution of functional Gal4 through the interaction of Gcr1 and Gcr2 proteins. The Gal4 (transcription-activating region)/Gcr1 fusion protein alone complemented the defects of both gcr1 and gcr2 strains. Furthermore, a Rap1/Gcr2 fusion protein partially complemented the defects of gcr1 strains. These results suggest that Gcr2 has transcriptional activation activity and that the GCR1 and GCR2 gene products function together. PMID- 1508188 TI - PTA1, an essential gene of Saccharomyces cerevisiae affecting pre-tRNA processing. AB - We have identified an essential Saccharomyces cerevisiae gene, PTA1, that affects pre-tRNA processing. PTA1 was initially defined by a UV-induced mutation, pta1-1, that causes the accumulation of all 10 end-trimmed, intron-containing pre-tRNAs and temperature-sensitive but osmotic-remedial growth. pta1-1 does not appear to be an allele of any other known gene affecting pre-tRNA processing. Extracts prepared from pta1-1 strains had normal pre-tRNA splicing endonuclease activity. pta1-1 was suppressed by the ochre suppressor tRNA gene SUP11, indicating that the pta1-1 mutation creates a termination codon within a protein reading frame. The PTA1 gene was isolated from a genomic library by complementation of the pta1 1 growth defect. Episome-borne PTA1 directs recombination to the pta1-1 locus. PTA1 has been mapped to the left arm of chromosome I near CDC24; the gene was sequenced and could encode a protein of 785 amino acids with a molecular weight of 88,417. No other protein sequences similar to that of the predicted PTA1 gene product have been identified within the EMBL or GenBank data base. Disruption of PTA1 near the carboxy terminus of the putative open reading frame was lethal. Possible functions of the PTA1 gene product are discussed. PMID- 1508189 TI - NSR1 is required for pre-rRNA processing and for the proper maintenance of steady state levels of ribosomal subunits. AB - NSR1 is a yeast nuclear localization sequence-binding protein showing striking similarity in its domain structure to nucleolin. Cells lacking NSR1 are viable but have a severe growth defect. We show here that NSR1, like nucleolin, is involved in ribosome biogenesis. The nsr1 mutant is deficient in pre-rRNA processing such that the initial 35S pre-rRNA processing is blocked and 20S pre rRNA is nearly absent. The reduced amount of 20S pre-rRNA leads to a shortage of 18S rRNA and is reflected in a change in the distribution of 60S and 40S ribosomal subunits; there is no free pool of 40S subunits, and the free pool of 60S subunits is greatly increased in size. The lack of free 40S subunits or the improper assembly of these subunits causes the nsr1 mutant to show sensitivity to the antibiotic paromomycin, which affects protein translation, at concentrations that do not affect the growth of the wild-type strain. Our data support the idea that NSR1 is involved in the proper assembly of pre-rRNA particles, possibly by bringing rRNA and ribosomal proteins together by virtue of its nuclear localization sequence-binding domain and multiple RNA recognition motifs. Alternatively, NSR1 may also act to regulate the nuclear entry of ribosomal proteins required for proper assembly of pre-rRNA particles. PMID- 1508190 TI - Alternative splicing of a human alpha-tropomyosin muscle-specific exon: identification of determining sequences. AB - The human alpha-tropomyosin gene hTMnm has two mutually exclusive versions of exon 5 (NM and SK), one of which is expressed specifically in skeletal muscle (exon SK). A minigene construct expresses only the nonmuscle (NM) isoform when transfected into COS-1 cells and both forms when transfected into myoblasts. Twenty-four mutants were produced to determine why the SK exon is not expressed in COS cells. The results showed that exons NM and SK are not in competition for splicing to the flanking exons and that there is no intrinsic barrier to splicing between the exons. Instead, exon SK is skipped whenever there are flanking introns. Splicing of exon SK was induced when the branch site sequence 70 nucleotides upstream of the exon was mutated to resemble the consensus and when the extremities of the exon itself were changed to the corresponding NM sequence. Precise swaps of the NM and SK exon sequences showed that the exon sequence effect was dominant to that of intron sequences. The mechanism of regulation appears to be unlike that of other tropomyosin genes. We propose that exclusion of exon SK arises because its 3' splicing signals are weak and are prevented by an exon-specific repressor from competing for splice site recognition. PMID- 1508191 TI - Overexpression of Mos, Ras, Src, and Fos inhibits mouse mammary epithelial cell differentiation. AB - Mammary epithelial cells terminally differentiate in response to lactogenic hormones. We present evidence that oncoprotein overexpression is incompatible with this hormone-inducible differentiation and results in striking cellular morphological changes. In mammary epithelial cells in culture, lactogenic hormones (glucocorticoid and prolactin) activated a transfected beta-casein promoter and endogenous beta-casein gene expression. This response to lactogenic hormone treatment was paralleled by a decrease in cellular AP-1 DNA-binding activity. Expression of the mos, ras, or src (but not myc) oncogene blocked the activation of the beta-casein promoter induced by the lactogenic hormones and was associated with the maintenance of high levels of AP-1. Mos expression also increased c-fos and c-jun mRNA levels. Overexpression of Fos and Jun from transiently transfected constructs resulted in a functional inhibition of the glucocorticoid receptor in these mouse mammary epithelial cells. This finding clearly suggests that glucocorticoid receptor inhibition arising from oncogene expression will contribute to the block in hormonally induced mammary epithelial cell differentiation. Expression of Src resulted in the loss of the normal organization and morphological phenotype of mammary epithelial cells in the epithelial/fibroblastic line IM-2. Activation of a conditional c-fos/estrogen receptor gene encoding an estrogen-dependent Fos/estrogen receptor fusion protein also morphologically transformed mammary epithelial cells and inhibited initiation of mammary epithelial differentiation-associated expression of the beta-casein and WDNM 1 genes. In response to estrogen treatment, the cells displayed a high level of AP-1 DNA-binding activity. Our results demonstrate that high cellular AP-1 levels contribute to blocking the ability of mammary epithelial cells in culture to respond to lactogenic hormones. This and other studies indicate that the oncogene products Mos, Ras, and Src exert their effects, at least in part, by stimulating cellular Fos and probably cellular Jun activity. PMID- 1508192 TI - Platelet-derived growth factor stimulation of GTPase-activating protein tyrosine phosphorylation in control and c-H-ras-expressing NIH 3T3 cells correlates with p21ras activation. AB - Platelet-derived growth factor (PDGF) stimulation of NIH 3T3 cells leads to the rapid tyrosine phosphorylation of the GTPase-activating protein (GAP) and an associated 64- to 62-kDa tyrosine-phosphorylated protein (p64/62). To assess the functions of these proteins, we evaluated their phosphorylation state in normal NIH 3T3 cells as well as in cells transformed by oncogenically activated v-H-ras or overexpression of c-H-ras genes. No significant GAP tyrosine phosphorylation was observed in unstimulated cultures, while PDGF-BB induced rapid tyrosine phosphorylation of GAP in all cell lines analyzed. In NIH 3T3 cells, we found that PDGF stimulation led to the recovery of between 37 and 52% of GAP molecules by immunoprecipitation with monoclonal antiphosphotyrosine antibodies. Furthermore, PDGF exposure led to a rapid and sustained increase in the levels of p21ras bound to GTP, with kinetics similar to those observed for GAP tyrosine phosphorylation. The PDGF-induced increases in GTP-bound p21ras in NIH 3T3 cells were comparable to the steady-state level observed in serum-starved c-H-ras overexpressing transformants, conditions in which these cells maintained high rates of DNA synthesis. These results imply that the level of p21ras activation following PDGF stimulation of NIH 3T3 cells is sufficient to support mitogenic stimulation. Addition of PDGF to c-H-ras-overexpressing cells also resulted in a rapid and sustained increase in GTP-bound p21ras. In these cells GAP, but not p64/62, showed increased tyrosine phosphorylation, with kinetics similar to those observed for increased GTP-bound p21ras. All of these findings support a role for GAP tyrosine phosphorylation in p21ras activation and mitogenic signaling. PMID- 1508193 TI - Growth factor-induced delayed early response genes. AB - Growth factors induce the sequential expression of cellular genes whose products are thought to mediate long-term responses to the growth factors. In mouse 3T3 fibroblastic cells, the first genes to be expressed (immediate-early genes) are activated within minutes after the addition of platelet-derived growth factor, fibroblast growth factor, or serum. By cDNA cloning, we have identified genes that are activated after a delay of a few hours and several hours prior to serum induced DNA replication. Activation of these delayed early response genes requires new protein synthesis, presumably the synthesis of immediate-early transcription factors described previously. Partial or complete sequencing of 13 different delayed early cDNAs, representing about 40% of the 650 primary cDNA isolates, revealed that 8 were related to known gene sequences and 5 were not. Among the former are cDNAs encoding nonhistone chromosomal proteins [HMGI(Y) and HMGI-C], adenine phosphoribosyltransferase (APRT), a protein related to human macrophage migration inhibitory factor (MIF), a protein of the major intrinsic protein (MIP) family homologous to the integral membrane protein of human erythrocytes, and cyclin CYL1. In 3T3 cells, the delayed early gene response to growth factors appears to be at least as complex as the immediate-early gene response previously described. PMID- 1508194 TI - A new member of the protein kinase C family, nPKC theta, predominantly expressed in skeletal muscle. AB - A new protein kinase C (PKC)-related cDNA with unique tissue distribution has been isolated and characterized. This cDNA encodes a protein, nPKC theta, which consists of 707 amino acid residues and showed the highest sequence similarity to nPKC delta (67.0% in total). nPKC theta has a zinc-finger-like cysteine-rich sequence (C1 region) and a protein kinase domain sequence (C3 region), both of which are common in all PKC family members. However, nPKC theta lacks a putative Ca2+ binding region (C2 region) that is seen only in the conventional PKC subfamily (cPKC alpha, -beta I, -beta II, and -gamma) but not in the novel PKC subfamily (nPKC delta, -epsilon, -zeta, and -eta). Northern (RNA) blot analyses revealed that the mRNA for nPKC theta is expressed predominantly in skeletal muscle. Furthermore, nPKC theta mRNA is the most abundantly expressed PKC isoform in skeletal muscle among the nine PKC family members. nPKC theta expressed in COS1 cells serves as a phorbol ester receptor. By the use of an antipeptide antibody specific to the D2-D3 region of the nPKC theta sequence, nPKC theta was recognized as a 79-kDa protein upon sodium dodecyl sulfate-polyacrylamide gel electrophoresis in mouse skeletal muscle extract and also in an extract from COS1 cells transfected with an nPKC theta cDNA expression plasmid. Autophosphorylation of immunoprecipitated nPKC theta was observed; it was enhanced by phosphatidylserine and 12-O-tetradecanoylphorbol-13-acetate but attenuated by the addition of Ca2+. These results clearly demonstrate that nPKC theta should be considered a member of the PKC family of proteins that play crucial roles in the signal transduction pathway. PMID- 1508195 TI - PRP38 encodes a yeast protein required for pre-mRNA splicing and maintenance of stable U6 small nuclear RNA levels. AB - An essential pre-mRNA splicing factor, the product of the PRP38 gene, has been genetically identified in a screen of temperature-sensitive mutants of Saccharomyces cerevisiae. Shifting temperature-sensitive prp38 cultures from 23 to 37 degrees C prevents the first cleavage-ligation event in the excision of introns from mRNA precursors. In vitro splicing inactivation and complementation studies suggest that the PRP38-encoded factor functions, at least in part, after stable splicing complex formation. The PRP38 locus contains a 726-bp open reading frame coding for an acidic 28-kDa polypeptide (PRP38). While PRP38 lacks obvious structural similarity to previously defined splicing factors, heat inactivation of PRP38, PRP19, or any of the known U6 (or U4/U6) small nuclear ribonucleoprotein-associating proteins (i.e., PRP3, PRP4, PRP6, and PRP24) leads to a common, unexpected consequence: intracellular U6 small nuclear RNA (snRNA) levels decrease as splicing activity is lost. Curiously, U4 snRNA, normally extensively base paired with U6 snRNA, persists in the virtual absence of U6 snRNA. PMID- 1508196 TI - Early meiotic transcripts are highly unstable in Saccharomyces cerevisiae. AB - Meiosis in Saccharomyces cerevisiae requires the induction of a large number of genes whose mRNAs accumulate at specific times during meiotic development. This study addresses the role of mRNA stability in the regulation of meiosis-specific gene expression. Evidence is provided below demonstrating that the levels of meiotic mRNAs are exquisitely regulated by both transcriptional control and RNA turnover. The data show that (i) early meiotic transcripts are extremely unstable when expressed during either vegetative growth or sporulation, and (ii) transcriptional induction, rather than RNA turnover, is the predominant mechanism responsible for meiosis-specific transcript accumulation. When genes encoding the early meiotic mRNAs are fused to other promoters and expressed during vegetative growth, their mRNA half-lives, of under 3 min, are among the shortest known in S. cerevisiae. Since these mRNAs are only twofold more stable when expressed during sporulation, we conclude that developmental regulation of mRNA turnover can be eliminated as a major contributor to meiosis-specific mRNA accumulation. The rapid degradation of the early mRNAs at all stages of the yeast life cycle, however, suggests that a specific RNA degradation system operates to maintain very low basal levels of these transcripts during vegetative growth and after their transient transcriptional induction in meiosis. Studies to identify specific cis-acting elements required for the rapid degradation of early meiotic transcripts support this idea. A series of deletion derivatives of one early meiosis-specific gene, SPO13, indicate that its mRNA contains determinants, located within the coding region, which contribute to the high instability of this transcript. Translation is another component of the degradation mechanism since frameshift and nonsense mutations within the SPO13 mRNA stabilize the transcript. PMID- 1508197 TI - Sequence analysis reveals homology between two proteins of the flagellar radial spoke. AB - Flagellar radial spokes contribute to the regulation of dynein arm activity and thus the pattern of flagellar bending. We have sequenced the genes for radial spoke protein 4 (RSP4) and RSP6, two of the five proteins that make up the radial spoke head in Chlamydomonas reinhardtii. The two genes, which are tightly linked genetically (B. Huang, G. Piperno, Z. Ramanis, and D.J.L. Luck, J. Cell Biol. 88:80-88, 1981), are separated by only 435 bp. They encode proline-rich polypeptides of 49.8 kDa (RSP4) and 48.8 kDa (RSP6), which are 48% identical to each other but do not resemble any previously sequenced proteins. The transcription start sites of these genes and an additional radial spoke protein gene, that for RSP3, were determined, and patterns of mRNA accumulation during flagellar regeneration were examined for the three radial spoke protein genes. These studies provide the molecular tools for a detailed analysis of radial spoke head function and assembly and for a determination of the mechanism by which the genes required to build a complex organelle are regulated. PMID- 1508198 TI - Identification of DNA elements cooperatively activating proopiomelanocortin gene expression in the pituitary glands of transgenic mice. AB - The proopiomelanocortin (POMC) gene is highly expressed in adult mouse pituitary anterior lobe corticotrophs and intermediate lobe melanotrophs. To identify the DNA elements important for this tissue-specific expression, we analyzed a series of POMC reporter genes in transgenic mice. A DNA fragment containing rat POMC 5' flanking sequences from -323 to -34 recapitulated both basal pituitary cell specific and hormonally stimulated expression in adult mice when fused to a heterologous thymidine kinase promoter. Developmental onset of the reporter gene expression lagged by 1 day but otherwise closely paralleled the normal ontogeny of murine POMC gene expression, including corticotroph activation at embryonic day 14.5 (E14.5) followed by melanotroph activation at E15.5 to E16.5. AtT20 corticotroph nuclear protein extracts interacted with three specific regions of the functional POMC promoter in DNase I protection assays. The positions of these protected sites were -107 to -160 (site 1), -182 to -218 (site 2), and -249 to 281 (site 3). Individual deletions of these footprinted sites did not alter transgene expression; however, the simultaneous deletion of sites 2 and 3 prevented transgene expression in both corticotrophs and melanotrophs. Electrophoretic mobility shift and Southwestern (DNA-protein) assays demonstrated that multiple AtT20 nuclear proteins bound to these footprinted sites. We conclude that the sequences between -323 and -34 of the rat POMC gene promoter are both necessary and sufficient for correct spatial, temporal, and hormonally regulated expression in the pituitary gland. Our data suggest that the three footprinted sites within the promoter are functionally interchangeable and act in combination with promoter elements between -114 and -34. The inability of any reporter gene construction to dissociate basal and hormonally stimulated expression suggests that these DNA elements are involved in both of these two characteristics of POMC gene expression in vivo. PMID- 1508199 TI - A transcriptionally active tRNA gene interferes with nucleosome positioning in vivo. AB - Incorporation into a positioned nucleosome of a cis-acting element essential for replication in Saccharomyces cerevisiae disrupts the function of the element in vivo [R. T. Simpson, Nature (London) 343:387-389, 1990]. Furthermore, nucleosome positioning has been implicated in repression of transcription by RNA polymerase II in yeast cells. We have now asked whether the function of cis-acting elements essential for transcription of a gene transcribed by RNA polymerase III can be similarly affected. A tRNA gene was fused to either of two nucleosome positioning signals such that the predicted nucleosome would incorporate near its center the tRNA start site and essential A-box element. These constructs were then introduced into yeast cells on stably maintained, multicopy plasmids. Competent tRNA genes were transcribed in vivo and were not incorporated into positioned nucleosomes. Mutated, inactive tRNA genes were incorporated into nucleosomes whose positions were as predicted. This finding demonstrates that the transcriptional competence of the tRNA gene determined its ability to override a nucleosome positioning signal in vivo and establishes that a hierarchy exists between cis-acting elements and nucleosome positioning signals. PMID- 1508200 TI - DPH5, a methyltransferase gene required for diphthamide biosynthesis in Saccharomyces cerevisiae. AB - A mutant of Saccharomyces cerevisiae defective in the S-adenosylmethionine (AdoMet)-dependent methyltransferase step of diphthamide biosynthesis was selected by intracellular expression of the F2 fragment of diphtheria toxin (DT) and shown to belong to complementation group DPH5. The DPH5 gene was cloned, sequenced, and found to encode a 300-residue protein with sequence similarity to bacterial AdoMet:uroporphyrinogen III methyltransferases, enzymes involved in cobalamin (vitamin B12) biosynthesis. Both DPH5 and AdoMet:uroporphyrinogen III methyltransferases lack sequence motifs commonly found in other methyltransferases and may represent a new family of AdoMet:methyltransferases. The DPH5 protein was produced in Escherichia coli and shown to be active in methylation of elongation factor 2 partially purified from the dph5 mutant. A null mutation of the chromosomal DPH5 gene did not affect cell viability, in agreement with other studies indicating that diphthamide is not required for cell survival. The dph5 null mutant survived expression of three enzymically attenuated DT fragments but was killed by expression of fully active DT fragment A. Consistent with these results, elongation factor 2 from the dph5 null mutant was found to have weak ADP-ribosyl acceptor activity, which was detectable only in the presence of high concentrations of fragment A. PMID- 1508201 TI - Establishment of a system for conditional gene expression using an inducible tRNA suppressor gene. AB - We investigated the use of the prokaryotic tetracycline operator-repressor system as a regulatory device to control the expression of Dictyostelium discoideum tRNA genes. The tetO1 operator fragment was inserted at three different positions in front of a tRNA(Glu) (Am) suppressor gene from D. discoideum, and the tetracycline repressor gene was expressed under the control of a constitutive actin 6 promoter. The effectiveness of this approach was determined by monitoring the expression of a beta-galactosidase gene engineered to contain a stop codon that could be suppressed by the tRNA. When these constructs were introduced into Dictyostelium cells, the repressor bound to the operator in front of the tRNA gene and prevented expression of the suppressor tRNA. Addition of tetracycline (30 micrograms/ml) to the growth medium prevented repressor binding, allowed expression of the suppressor tRNA, and resulted in beta-galactosidase synthesis. The operator-repressor complex interfered with tRNA gene transcription when the operator was inserted immediately upstream (position +1 or -7) of the mature tRNA coding region. Expression of a tRNA gene carrying the operator at position -46 did not respond to repressor binding. This system could be used to control the synthesis of any protein, provided the gene contained a translational stop signal. PMID- 1508202 TI - Replication forks pause at yeast centromeres. AB - The 120 bp of yeast centromeric DNA is tightly complexed with protein to form a nuclease-resistant core structure 200 to 240 bp in size. We have used two dimensional agarose gel electrophoresis to analyze the replication of the chromosomal copies of yeast CEN1, CEN3, and CEN4 and determine the fate of replication forks that encounter the protein-DNA complex at the centromere. We have shown that replication fork pause sites are coincident with each of these centromeres and therefore probably with all yeast centromeres. We have analyzed the replication of plasmids containing mutant derivatives of CEN3 to determine whether the replication fork pause site is a result of an unusual structure adopted by centromere DNA or a result of the protein-DNA complex formed at the centromere. The mutant centromere derivatives varied in function as well as the ability to form the nuclease-resistant core structure. The data obtained from analysis of these derivatives indicate that the ability to cause replication forks to pause correlates with the ability to form the nuclease-resistant core structure and not with the presence or absence of a particular DNA sequence. Our findings further suggest that the centromere protein-DNA complex is present during S phase when replication forks encounter the centromere and therefore may be present throughout the cell cycle. PMID- 1508203 TI - Kappa B site-dependent activation of the interleukin-2 receptor alpha-chain gene promoter by human c-Rel. AB - The cis-acting control elements of the interleukin-2 receptor alpha-chain (IL-2R alpha) gene contain a potent kappa B-like enhancer whose activity can be induced by various mitogenic stimuli. Recent cloning of the p50 and p65 subunits of the kappa B-binding protein NF-kappa B complex revealed a striking sequence homology of these proteins with the c-rel proto-oncogene product (c-Rel). On the basis of this homology, we examined the potential role of c-Rel in controlling IL-2R alpha transcription. We now demonstrate that the recombinant human c-Rel protein binds to the kappa B element in the IL-2R alpha promoter and results in alteration of the DNA structure in the adjacent downstream regulatory elements containing the CArG box and the GC box. We found that human c-Rel can activate transcription from the IL-2R alpha promoter, but not the kappa B-containing human immunodeficiency virus type 1 promoter, upon cotransfection into Jurkat T cells. Furthermore, truncation of the carboxyl terminus of c-Rel results in a c-Rel mutant (RelNA) that (i) localizes exclusively in the nucleus and (ii) acts in synergy with wild-type c-Rel in activating transcription from the kappa B site of the IL-2R alpha promoter. Finally, induction of surface IL-2R alpha expression coincides with the induced levels of endogenous c-Rel and induced c-Rel binding to the IL-2R alpha kappa B site. Our study identified c-Rel as one component of the Rel/NF-kappa B-family proteins involved in the kappa B-dependent activation of IL-2R alpha gene expression. Furthermore, our results suggest that a Re1NA like cellular factor (e.g., NF-kappa B p50 or p49 subunit) acts in synergy with c Re1 during T-cell activation. PMID- 1508204 TI - The DNA-binding defect observed in major histocompatibility complex class II regulatory mutants concerns only one member of a family of complexes binding to the X boxes of class II promoters. AB - The X box of major histocompatibility complex class II promoters is essential for proper expression of class II genes. Here we show that two distinct protein-DNA complexes (A and B), which exhibit similar binding characteristics and identical contact points on the X box, can be formed. This suggests the existence of a family of related X box-binding factors. Complex B (and not complex A) is specifically affected in primary combined immunodeficiency, a congenital defect in class II gene regulation. RFX1, the first X box-binding protein cloned, encodes a functionally relevant factor present in complex A and not in complex B as originally suspected. This report also illustrates the need for caution in correlating specific cloned proteins with nuclear factors identified by DNA binding assays, particularly when dealing with families of related proteins. PMID- 1508205 TI - Functional interaction between p21rap1A and components of the budding pathway in Saccharomyces cerevisiae. AB - The rap1A gene encodes a 21-kDa, ras-related GTP-binding protein (p21rap1A) of unknown function. A close structural homolog of p21rap1A (65% identity in the amino-terminal two-thirds) is the RSR1 gene product (Rsr1p) of Saccharomyces cerevisiae. Although Rsr1p is not essential for growth, its presence is required for nonrandom selection of bud sites. To assess the similarity of these proteins at the functional level, wild-type and mutant forms of p21rap1A were tested for complementation of activities known to be fulfilled by Rsr1p. Expression of p21rap1A, like multicopy expression of RSR1, suppressed the conditional lethality of a temperature-sensitive cdc24 mutation. Point mutations predicted to affect the localization of p21rap1A or its ability to cycle between GDP and GTP-bound states disrupted suppression of cdc24ts, while other mutations in the 61-65 loop region improved suppression. Expression of p21rap1A could not, however, suppress the random budding phenotype of rsr1 cells. p21rap1A also apparently interfered with the normal activity of Rsrlp, causing random budding in diploid wild-type cells, suggesting an inability of p21rap1A to interact appropriately with Rsr1p regulatory proteins. Consistent with this hypothesis, we found an Rsr1p-specific GTPase-activating protein (GAP) activity in yeast membranes which was not active toward p21rap1A, indicating that p21rap1A may be predominantly GTP bound in yeast cells. Coexpression of human Rap1-specific GAP suppressed the random budding due to expression of p21rap1A or its derivatives, including Rap1AVal-12. Although Rap1-specific GAP stimulated the GTPase of Rsr1p in vitro, it did not dominantly interfere with Rsr1p function in vivo. A chimera consisting of Rap1A1 165::Rsr1p166-272 did not exhibit normal Rsr1p function in the budding pathway. These results indicated that p21rap1A and Rsr1p share at least partial functional homology, which may have implications for p21rap1A function in mammalian cells. PMID- 1508206 TI - Drosophila transcriptional repressor protein that binds specifically to negative control elements in fat body enhancers. AB - Expression of the Drosophila melanogaster Adh gene in adults requires a fat body specific enhancer called the Adh adult enhancer (AAE). We have identified a protein in Drosophila nuclear extracts that binds specifically to a site within the AAE (adult enhancer factor 1 [AEF-1]). In addition, we have shown that AEF-1 binds specifically to two other Drosophila fat body enhancers. Base substitutions in the AEF-1 binding site that disrupt AEF-1 binding in vitro result in a significant increase in the level of Adh expression in vivo. Thus, the AEF-1 binding site is a negative regulatory element within the AAE. A cDNA encoding the AEF-1 protein was isolated and shown to act as a repressor of the AAE in cotransfection studies. The AEF-1 protein contains four zinc fingers and an alanine-rich sequence. The latter motif is found in other eukaryotic proteins known to be transcriptional repressors. PMID- 1508207 TI - Activation of heat shock factor 2 during hemin-induced differentiation of human erythroleukemia cells. AB - Hemin induces nonterminal differentiation of human K562 erythroleukemia cells, which is accompanied by the expression of certain erythroid cell-specific genes, such as the embryonic and fetal globins, and elevated expression of the stress genes hsp70, hsp90, and grp78/BiP. Previous studies revealed that, as during heat shock, transcriptional induction of hsp70 in hemin-treated cells is mediated by activation of heat shock transcription factor (HSF), which binds to the heat shock element (HSE). We report here that hemin activates the DNA-binding activity of HSF2, whereas heat shock induces predominantly the DNA-binding activity of a distinct factor, HSF1. This constitutes the first example of HSF2 activation in vivo. Both hemin and heat shock treatments resulted in equivalent levels of HSF HSE complexes as analyzed in vitro by gel mobility shift assay, yet transcription of the hsp70 gene was stimulated much less by hemin-induced HSF than by heat shock-induced HSF. Genomic footprinting experiments revealed that hemin-induced HSF and heat shock-induced HSF, HSF2, and HSF1, respectively, occupy the HSE of the human hsp70 promoter in a similar yet not identical manner. We speculate that the difference in occupancy and/or in the transcriptional abilities of HSF1 and HSF2 accounts for the observed differences in the stimulation of hsp70 gene transcription. PMID- 1508208 TI - A cyclic AMP-responsive element-binding transcriptional activator in Drosophila melanogaster, dCREB-A, is a member of the leucine zipper family. AB - In this report, we describe the isolation and initial characterization of a Drosophila protein, dCREB-A, that can bind the somatostatin cyclic AMP (cAMP) responsive element and is capable of activating transcription in cell culture. Sequence analysis demonstrates that this protein is a member of the leucine zipper family of transcription factors. dCREB-A is unusual in that it contains six hydrophobic residue iterations in the zipper domain rather than the four or five commonly found in this group of proteins. The DNA-binding domain is more closely related to mammalian CREB than to the AP-1 factors in both sequence homology and specificity of cAMP-responsive element binding. In embryos, dCREB-A is expressed in the developing salivary gland. A more complex pattern of expression is detected in the adult; transcripts are found in the brain and optic lobe cell bodies, salivary gland, and midgut epithelial cells of the cardia. In females, dCREB-A is expressed in the ovarian columnar follicle cells, and in males, dCREB-A RNA is seen in the seminal vesicle, ejaculatory duct, and ejaculatory bulb. These results suggest that the dCREB-A transcription factor may be involved in fertility and neurological functions. PMID- 1508209 TI - Formation of the 3' end of sea urchin U1 small nuclear RNA occurs independently of the conserved 3' box and on transcripts initiated from a histone promoter. AB - The formation of the 3' end of vertebrate small nuclear RNAs (snRNAs) requires that transcription initiate from an snRNA promoter. There is a loosely conserved required box 5 to 20 nucleotides (nt) 3' of the gene. The sea urchin snRNA genes contain promoter elements different from those of the vertebrate snRNAs. They also contain a characteristic 3' 15-nt sequence which is conserved among different sea urchin snRNA genes. We used microinjection of sea urchin U1 snRNA genes into sea urchin zygotes to define the sequence requirements for U1 snRNA 3' end formation. Surprisingly, the conserved 3' box is not required for efficient 3'-end formation in vivo. Deletion analysis reveals that the 6 nt immediately 3' of the U1 snRNA are involved in 3'-end formation. Substitution analysis revealed that either these 6 nt 3' of the U1 RNA or the conserved 3' box could direct 3' end formation. Transcripts initiated from a histone H4 promoter formed U1 3' ends about 50% as efficiently as transcripts initiated from the U1 promoter, even when the U1 end was placed in tandem with a histone 3'-processing signal, suggesting that transcription from an snRNA promoter is not necessary for formation of the 3' end of sea urchin U1 snRNA. PMID- 1508210 TI - Genetic interaction between transcription elongation factor TFIIS and RNA polymerase II. AB - Little is known about the regions of RNA polymerase II (RNAPII) that are involved in the process of transcript elongation and interaction with elongation factors. One elongation factor, TFIIS, stimulates transcript elongation by binding to RNAPII and facilitating its passage through intrinsic pausing sites in vitro. In Saccharomyces cerevisiae, TFIIS is encoded by the PPR2 gene. Deletion of PPR2 from the yeast genome is not lethal but renders cells sensitive to the uracil analog 6-azauracil (6AU). Here, we show that mutations conferring 6AU sensitivity can also be isolated in the gene encoding the largest subunit of S. cerevisiae RNAPII (RPO21). A screen for mutations in RPO21 that confer 6AU sensitivity identified seven mutations that had been generated by either linker-insertion or random chemical mutagenesis. All seven mutational alterations are clustered within one region of the largest subunit that is conserved among eukaryotic RNAPII. The finding that six of the seven rpo21 mutants failed to grow at elevated temperature underscores the importance of this region for the functional and/or structural integrity of RNAPII. We found that the 6AU sensitivity of the rpo21 mutants can be suppressed by increasing the dosage of the wild-type PPR2 gene, presumably as a result of overexpression of TFIIS. These results are consistent with the proposal that in the rpo21 mutants, the formation of the RNAPII-TFIIS complex is rate limiting for the passage of the mutant enzyme through pausing sites. In addition to implicating a region of the largest subunit of RNAPII in the process of transcript elongation, our observations provide in vivo evidence that TFIIS is involved in transcription by RNAPII. PMID- 1508211 TI - Identification of an early-growth-response gene encoding a novel putative protein kinase. AB - Early-growth-response genes, also known as immediate-early genes, play important roles in regulating cell proliferation. We have identified a new type of early growth-response gene product, a 77,811-Da putative serine/threonine kinase, which is highly inducible by serum and phorbol ester. mRNA encoding this putative kinase is markedly elevated within 1 h after treatment with mitogen, and this induction is synergistically increased by cycloheximide. Dexamethasone blocks serum induction of the kinase mRNA, as does transformation by v-Ki-ras. The kinase mRNA was detected in mouse brain, lung, and heart. This new putative kinase, which we term Snk, for serum-inducible kinase, showed similarity in its proposed catalytic domain to many other protein kinases; however, no other kinase showed enough sequence similarity with Snk to suggest the existence of a common function. Hence, Snk represents a new type of protein kinase involved in the early mitogenic response whose activity is transcriptionally and posttranscriptionally regulated. PMID- 1508212 TI - Functional analysis of the human adenosine deaminase gene thymic regulatory region and its ability to generate position-independent transgene expression. AB - We previously observed that human ADA gene expression, required for the intrathymic maturation of T cells, is controlled by first-intron sequences. Used as a cis activator, the intron generates copy-dependent reporter expression in transgenic thymocytes, and we here dissect its critical determinants. Of six DNase I-hypersensitive sites (HS sites) in the intron, only HS III was a transfection-active classic enhancer in T cells. The enhancer contains a critical core region, ACATGGCAGTTGGTGGTGGAGGGGAACA, that interacts with at least two factors, ADA-NF1 and ADA-NF2. Activity of the core is strongly augmented by adjacent elements contained within a 200-bp domain corresponding to the limits of HS III hypersensitivity. These core-adjacent sequences include consensus matches for recognition by the AP-1, TCF-1 alpha, mu E, and Ets transcription factor families. In contrast, considerably more extensive sequences flanking the enhancer domain were required for position-independent and copy-proportional expression in transgenic mouse thymocytes. The additionally required upstream segment encompassed the nonenhancer HS II site. The required downstream segment, composed largely of Alu-repetitive DNA, was non-DNase I hypersensitive. Transgenes that lacked either segment were subject to strong positional effects. Among these variably expressing lines, the expression level correlated with the degree of hypersensitivity at HS III. This finding suggests that formation of hypersensitivity is normally facilitated by the flanking segments. These results delineate a complex thymic regulatory region within the intron and indicate that a series of interactions is necessary for the enhancer domain to function consistently within chromatin. PMID- 1508213 TI - Thymic overexpression of Ttg-1 in transgenic mice results in T-cell acute lymphoblastic leukemia/lymphoma. AB - T-cell translocation gene 1 (Ttg-1), also called rhombotin, is deregulated upon translocation into the alpha/delta T-cell receptor loci in acute lymphoblastic leukemias bearing the t(11;14)(p15;q11). Ttg-1 encodes a nuclear protein, expressed predominantly in neuronal cells, which belongs to a novel family of transcription factors possessing LIM domains. We utilized the lck proximal promoter to overexpress this candidate oncogene in immature thymocytes of transgenic mice. lckPr Ttg-1 mice develop immature, aggressive T-cell leukemia/lymphomas. Tumor incidence is proportional to the level of Ttg-1 expression. Most tumors contain CD4+8+ cells as well as CD4-8+ cells, which have an immature rather than a mature peripheral phenotype. Ttg-1-induced tumorigenesis preferentially affects a minority population of thymocytes representing an immature CD4-8+ intermediate stage between double-negative CD4-8- cells and double-positive CD4+8+ cells. This model indicates that the aberrant expression of putative transcription factors plays a primary role in the genesis of T-cell acute lymphoblastic leukemias. PMID- 1508214 TI - Functional antagonism between YY1 and the serum response factor. AB - The rapid, transient induction of the c-fos proto-oncogene by serum growth factors is mediated by the serum response element (SRE). The SRE shares homology with the muscle regulatory element (MRE) of the skeletal alpha-actin promoter. It is not known how these elements respond to proliferative and cell-type-specific signals, but the response appears to involve the binding of the serum response factor (SRF) and other proteins. Here, we report that YY1, a multifunctional transcription factor, binds to SRE and MRE sequences in vitro. The methylation interference footprint of YY1 overlaps with that of the SRF, and YY1 competes with the SRF for binding to these DNA elements. Overexpression of YY1 repressed serum-inducible and basal expression from the c-fos promoter and repressed basal expression from the skeletal alpha-actin promoter. YY1 also repressed expression from the individual SRE and MRE sequences upstream from a TATA element. Unlike that of YY1, SRF overexpression alone did not influence the transcriptional activity of the target sequence, but SRF overexpression could reverse YY1 mediated trans repression. These data suggest that YY1 and the SRF have antagonistic functions in vivo. PMID- 1508215 TI - Identification of pre-mRNA polyadenylation sites in Saccharomyces cerevisiae. AB - In contrast to higher eukaryotes, little is known about the nature of the sequences which direct 3'-end formation of pre-mRNAs in the yeast Saccharomyces cerevisiae. The hexanucleotide AAUAAA, which is highly conserved and crucial in mammals, does not seem to have any functional importance for 3'-end formation in yeast cells. Instead, other elements have been proposed to serve as signal sequences. We performed a detailed investigation of the yeast ACT1, ADH1, CYC1, and YPT1 cDNAs, which showed that the polyadenylation sites used in vivo can be scattered over a region spanning up to 200 nucleotides. It therefore seems very unlikely that a single signal sequence is responsible for the selection of all these polyadenylation sites. Our study also showed that in the large majority of mRNAs, polyadenylation starts directly before or after an adenosine residue and that 3'-end formation of ADH1 transcripts occurs preferentially at the sequence PyAAA. Site-directed mutagenesis of these sites in the ADH1 gene suggested that this PyAAA sequence is essential for polyadenylation site selection both in vitro and in vivo. Furthermore, the 3'-terminal regions of the yeast genes investigated here are characterized by their capacity to act as signals for 3'-end formation in vivo in either orientation. PMID- 1508216 TI - Pax-8, a paired domain-containing protein, binds to a sequence overlapping the recognition site of a homeodomain and activates transcription from two thyroid specific promoters. AB - The Pax-8 gene, a member of the murine family of paired box-containing genes (Pax genes), is expressed in adult thyroid and in cultured thyroid cell lines. The Pax 8 protein binds, through its paired domain, to the promoters of thyroglobulin and thyroperoxidase, genes that are exclusively expressed in the thyroid. In both promoters, the binding site of Pax-8 overlaps with that of TTF-1, a homeodomain containing protein involved in the activation of thyroid-specific transcription. Pax-8 activates transcription from cotransfected thyroperoxidase and thyroglobulin promoters, indicating that it may be involved in the establishment, control, or maintenance of the thyroid-differentiated phenotype. Thus, the promoters of thyroglobulin and thyroperoxidase represent the first identified natural targets for transcriptional activation by a paired domain-containing protein. PMID- 1508217 TI - Endothelin induces transcription of fos/jun family genes: a prominent role for calcium ion. AB - The 21-amino acid mammalian peptide endothelin (ET) is a powerful vasoconstrictor, a mitogen for fibroblasts and vascular smooth muscle cells, and a potent effector for numerous tissues. Through extracellular interaction with G protein-coupled transmembrane receptors, ET stimulates intracellular second messenger events that in turn activate immediate early gene transcription. Using Northern blot hybridization and nuclear run-on analyses, we examined the modulation of c-fos, fos-B, fra-1, c-jun, and jun-B gene transcripts in Rat-1 fibroblasts after ET treatment. Furthermore, we investigated the role that intracellular Ca2+ transients played in effecting this gene regulation, using the intracellular Ca2+ chelator 1,2-bis(o-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid (BAPTA) to block Ca(2+)-dependent transcription. Our results demonstrate that ET rapidly effects increased RNA levels for all five fos/jun family genes investigated, at least two of them by increasing gene transcription. Furthermore, our results argue that increased intracellular free Ca2+ is directly involved in the induction of these fos/jun family genes by ET. While mobilization of intracellular Ca2+ is not the only pathway to fos/jun gene induction used by ET, it is clearly a major component of the signaling apparatus that is set in motion by this potent effector. PMID- 1508218 TI - Expression of prolactin and its receptor in human lymphoid cells. AB - We have investigated whether human lymphoid cells are able to synthesize and secrete human PRL (hPRL) and to express PRL receptors. Metabolic labeling with [35S]methionine and immunoprecipitation of cell extracts from human mononuclear cells (MNC) and a human T lymphocyte cell line with an antiserum against hPRL revealed protein of M(r) 23,000, identical in size to pituitary hPRL. Dilution curves of lymphocyte immunoreactive hPRL were parallel to those obtained with pituitary hPRL in an immunoradiometric assay using two monoclonal antibodies against hPRL. Polymerase chain reaction experiments with primers located in the coding sequence of hPRL showed that the hPRL gene was expressed in MNC. Furthermore, cDNA cloning and sequence analysis indicated the presence of an extra 5' noncoding exon previously described for decidual hPRL. When MNCs were further separated into B cells, T cells, and monocytes, the expression of hPRL appeared to be mainly associated with the T lymphocyte fraction. The hPRL transcript was also detected in thymocytes and in a set of human lymphoid cell lines. Finally, polymerase chain reaction experiments revealed a ubiquitous distribution of PRL receptor gene expression in B cells, T cells, and monocytes. The presence of the receptor for PRL and production of PRL by T lymphocytes suggest a possible autocrine or paracrine effect of PRL in immune cell function. PMID- 1508219 TI - Differential expression of the mouse mitochondrial genes and the mitochondrial RNA-processing endoribonuclease RNA by androgens. AB - Using subtractive hybridization to identify genes that are androgen regulated in the mouse epididymis, a number of cDNAs were identified that represented mitochondrial genes including cytochrome oxidase c subunits I, II, and III, cytochrome b, NADH dehydrogenase subunit 5, a region of the displacement loop, and the 16S rRNA. Northern blot analysis of RNA from intact, castrate, or testosterone-replaced epididymides confirmed that these mitochondrial mRNAs as well as the rRNA were androgen regulated with a 2- to 5-fold reduction in expression observed after 4 weeks castration with partial to full recovery to precastrate levels upon 4 weeks of testosterone replacement. In contrast to the mitochondrial genes, the expression of the RNA component of the mitochondrial RNA processing endoribonuclease (RNAase MRP), a nuclear factor which is thought to be involved in the regulation of mitochondrial DNA synthesis, increased in the epididymis upon castration and then returned to precastrate levels after testosterone replacement. An examination of other androgen-responsive tissues showed that mitochondrial gene expression was also regulated by androgens in the kidney. The RNAase MRP RNA levels, however, showed an increase after castration only in the reproductive tissues (epididymis, vas deferens, and seminal vesicle) and not in the kidney. No correlative increase in mitochondrial DNA levels was observed for any of the tissues. Finally, an analysis of various mouse tissues as well as the different regions of the epididymis revealed large differences in mitochondrial mRNA levels. While for most tissues the mRNA levels correlated with the mitochondrial DNA content, the levels of the RNAase MRP RNA did not. Taken together, these findings not only show the large variations in mitochondrial gene expression between tissues but also demonstrate that the expression of mitochondrial genes and ultimately mitochondrial function are androgen regulated in the epididymis and kidney. PMID- 1508220 TI - Ligand-dependent and -independent function of the transactivation regions of the human estrogen receptor in yeast. AB - The estrogen receptor (ER) is a transcription factor involved in steroid hormone signal transduction in higher eukaryotes. The receptor also functions as a ligand dependent transcriptional activator when introduced into Saccharomyces cerevisiae (baker's yeast), which suggests that at least some of the components of the signal transduction pathway are conserved between yeast and mammalian cells, and, moreover, allows the possibility of using this simple eukaryotic organism to dissect receptor function. However, whether the ER actually activates transcription in a mechanistically similar fashion in yeast and mammalian cells is unclear, since it has been reported that the transactivation function within the hormone binding domain (TAF-2) does not function in yeast. In this report, we have characterized the activity of the transactivation functions of the ER in yeast. Our results indicate that both TAF-2 and the N-terminal transactivation region (TAF-1) are functional in yeast and contribute synergistically to the receptor's total activity. These results are consistent with those obtained in mammalian cells. Furthermore, we show that in yeast the antagonistic effects of the antiestrogen nafoxidine arise from a modulation of the synergistic interactions of TAF-1 and TAF-2, and not simply from an inactivation of TAF-2 by antihormone. Finally, we characterize the effect of ER deletion mutants on chromatin structure in yeast. Our data lend support to the view that the formation of competent transcriptional initiation complexes requires a precise disruption of chromatin structure. PMID- 1508221 TI - Differential promoter usage by the rat 11 beta-hydroxysteroid dehydrogenase gene. AB - 11 beta-hydroxysteroid dehydrogenase (11 beta-OHSD) catalyzes the conversion of physiological glucocorticoids to inactive products, thus protecting nonselective renal mineralocorticoid receptors from circulating glucocorticoids (ensuring aldosterone selectivity in vivo) and modulating glucocorticoid access to mineralocorticoid receptors and glucocorticoid receptors in other tissues. Detection of multiple mRNA and immunoreactive 11 beta-OHSD species in kidney, but not liver, extracts suggests the presence of tissue-specific isoforms. To determine whether differential promoter usage might explain the mRNA heterogeneity we cloned and sequenced rat 11 beta-OHSD genomic DNA. Total identity was found between the nucleotide sequence of exons 1 and 2 and the previously published rat liver cDNA. Using both primer extension and RNase protection analyses we found the predominant transcription start site in liver (+1) is 105 base pairs (bp)5' of the start of translation. In kidney two additional Cap sites were detected: 1) 264 bp 5' of exon 1; there is no in-phase open reading frame, suggesting the additional 5' sequence is not translated; and 2) 65 bp upstream of exon 2, within intron A; the predicted truncated protein lacks the first 26 hydrophobic residues. Oligonucleotide probes specific to transcripts arising from each promoter confirmed that all three are employed in kidney, whereas a single predominant species was found in liver, thus demonstrating tissue-specific differential promoter usage of the 11 beta-OHSD gene. PMID- 1508222 TI - Biosynthesis of the prohormone convertase mPC1 in AtT-20 cells. AB - A new family of mammalian subtilisin-like enzymes, probably involved in the processing of proproteins in regulated and constitutive cells at paired basic residues, has recently been discovered. Little information exists as yet concerning the biosynthesis of these endogenous subtilisin-like enzymes. In the present work the biosynthesis and release of the endogenous prohormone convertase PC1 in AtT-20 cells were studied. As predicted from mRNA studies, AtT-20 cells contain high levels of PC1 protein. Through immunoblotting, 87-kilodalton (kDa) and 66-kDa bands were detected with an amino terminally directed antiserum; however, only the 87-kDa product was detected with carboxyl terminally directed antiserum, indicating carboxyl terminal truncation. Pulse-chase experiments, using [35S]methionine/cysteine, showed that after 20 min pulse the main product in the cells was the 87-kDa protein. Cells chased for varying amounts of time exhibited a progressive increase in the intensity of a 66-kDa band, along with a corresponding decrease of the 87-kDa band. The 87-66 kDa conversion was nearly complete after 4 h of chase. This posttranslational processing was inhibited by the ionophore monensin, a Golgi disruptor, with a corresponding accumulation of the 87-kDa protein within the cell. Both the 87 kDa- and 66 kDa-labeled proteins were detected as membrane-bound rather than soluble proteins. The 87-kDa protein was the main product secreted by nonstimulated AtT-20 cells, while the 66-kDa product was only released when the cells were stimulated with CRF or BaCl2 and Bromo-cAMP.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1508223 TI - Complete androgen insensitivity due to deletion of exon C of the androgen receptor gene highlights the functional importance of the second zinc finger of the androgen receptor in vivo. AB - Androgen-dependent gene transcription is mediated by the androgen receptor (AR) through interaction of its central zinc finger region with specific DNA sequences on target genes. Failure of this receptor-mediated gene transcription results in end organ resistance to androgens-the androgen insensitivity syndromes. In a pair of siblings with complete androgen insensitivity who had supranormal levels of androgen binding in genital skin fibroblasts, polymerase chain reaction and Southern blot analysis of the androgen receptor gene confirmed by polymerase chain reaction and sequence analysis of AR cDNA, revealed an in-frame deletion of exon C encoding the second zinc finger of the receptor. The mutant receptor in cultured genital skin fibroblasts had normal androgen binding affinity and was localized in the nucleus but had markedly reduced DNA-binding affinity. When recreated in vitro and tested in a cotransfection assay system the mutant receptor failed to activate transcription of an androgen-responsive reporter gene. This naturally occurring mutation highlights the functional dependence of the AR upon its second zinc finger in vivo and explains the complete insensitivity to androgen manifest by the affected individuals despite increased androgen binding. The elevated AR levels in the subjects' genital skin fibroblasts further suggests a possible role for the second zinc finger in autoregulation of receptor levels in vivo. PMID- 1508224 TI - Genetic analysis of the human type-1 angiotensin II receptor. AB - Angiotensin II is a potent pressor hormone and a primary regulator of aldosterone secretion. It acts through at least two types of receptors termed AT1 and AT2. We analyzed cDNA and genomic clones encoding the human angiotensin II type-1 receptor, AT1. The human AT1 gene was mapped to chromosome 3q by polymerase chain reaction analysis of DNA from a panel of human-hamster somatic cell hybrids. The predicted amino acid sequence is 95% identical to the corresponding rat and bovine receptors and 25% and 22% identical, respectively, to the receptors encoded by the RTA and MAS genes. Characterization of several human cDNA clones demonstrated the existence of two alternate 5'-untranslated regions (UTRs) that contain a common initial sequence but differ by the presence or absence of an insertion of 84 base pairs. In the genomic sequence, the coding sequences are contained in a single exon, with an intron occurring in the 5'-UTR at the position of insertion of the 84-base pair sequence. The exons encoding the alternate 5'-UTRs are located at least 3.8 kilobases away from the exon encoding the protein. Reverse transcription-polymerase chain reaction analysis showed that both forms of 5'-UTR are present in approximately equal abundance in a range of tissues expressing AT1. The reagents developed in this work may be useful in testing the hypothesis that genetic variations in angiotensin II receptor function are associated with a tendency to develop hypertension. PMID- 1508226 TI - CCAAT/enhancer binding protein expression is rapidly extinguished in TA1 adipocyte cells treated with tumor necrosis factor. AB - Tumor necrosis factor (TNF) has been shown to have diverse effects on a wide variety of cell types. In the mouse adipogenic TA1 cell line, TNF completely abolishes differentiation and reverts fully differentiated fat cells into fibroblasts. This block in differentiation and its reversal is due to the rapid reduction in the expression of adipose-specific genes. This study reports that the transcription factor, CCAAT/enhancer binding protein (C/EBP), previously reported to promote the differentiation of 3T3-L1 adipocytes, is expressed in TA1 cells. During their growth in culture, the levels of C/EBP, as evidenced by its cellular levels of specific mRNA, protein, and DNA binding activity, increase dramatically when cells reach confluence and proceed to differentiate. Addition of TNF to cultured preadipocytes or fully differentiated adipocytes rapidly reduces C/EBP levels and is accompanied by the decrease in expression of adipose specific genes. C/EBP binding sites occur in several adipose-specific genes, and here it is demonstrated that its presence in a novel adipose-specific gene, Clone 47, also referred to as FSP27, may be responsible for the strong down-regulation of the expression of the Clone 47 (FSP27) promoter-linked chloramphenicol acetyl transferase gene by TNF. This study proposes that the loss of C/EBP in response to TNF treatment may in part explain the loss of the adipocyte differentiated state. PMID- 1508225 TI - The role of asparagine-linked oligosaccharides in the subunit structure, steroid binding, and secretion of androgen-binding protein. AB - Testicular androgen-binding protein (ABP) and liver sex hormone-binding globulin are encoded by the same gene. These proteins have the same primary amino acid sequences, but they differ in attached oligosaccharides; the differences are presumably due to cell-specific glycosylation mechanisms. To investigate the role of oligosaccharides in ABP/sex hormone-binding globulin subunit structure, secretion, and steroid binding, mutant rat ABP proteins were constructed that eliminated one or both of the two potential sites of asparagine (Asn)-linked glycosylation. Immunoblot analysis of wild type recombinant ABP yielded the typical heterogeneous banding pattern. Secreted ABP was composed of two protomers of M(r) 46,000 and M(r) 43,000, while cellular ABP yielded three mol wt species (M(r) 43,000, 41,000, and 39,000). Substitution of the Asn residue in either consensus sequence for Asn-linked glycosylation with an Ile residue resulted in increased mobility of the immunoreactive ABP species. These changes are consistent with the loss of an Asn-linked oligosaccharide. Substitution of both Asn residues yielded a single immunoreactive species in the medium and cell extracts that migrated as a M(r) 39,000 protein. These results demonstrate that the mol wt heterogeneity of ABP is due to differential Asn-linked glycosylation of both potential sites. All three mutant forms of ABP were secreted by the COS cells. However, the amount of immunoreactive ABP and [3H]5 alpha dihydrotestosterone binding in the medium was lower than wild type (100%) in one of the single mutants (65%) and in the double mutant (29%). Unlike the glycosylation mutants, alteration of other residues, not involved in glycosylation, yielded cellular ABP and no detectable medium ABP.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1508227 TI - Thyroid hormone alters in vitro DNA binding of monomers and dimers of thyroid hormone receptors. AB - T3 binds to intranuclear thyroid hormone receptors (TRs) on target DNA elements and exerts profound influences on gene expression by mechanisms not yet characterized. We used gel shift assays and cross-linking experiments to demonstrate that T3 greatly induced the monomeric binding of the hTR beta produced in Escherichia coli to DNA. T3 also increased the gel mobility of these monomer-DNA complexes suggesting they undergo a ligand-induced conformational change. This effect did not depend on the orientation and spacing of the half site motifs within the DNA structure. In contrast, T3 had diverse effects on the dimeric interaction. T3 increased the dimeric interaction to the palindrome GGTCA.TGACC (an effect lost by spacing the half-sites with 3 base pairs) and decreased the dimeric interaction to the inverted palindrome containing the TGACC.GGTCA motif. Scatchard analyses indicated that the T3 enhancement on binding was due to an increase in the number of TR with high affinity DNA-binding activity and not by increasing the affinity of TR that could bind to DNA. The effects of various T3 analogs were directly related to their affinities for the TR. These ligand effects on in vitro TR-DNA binding may reflect mechanisms by which T3 regulates transcription in vivo. PMID- 1508228 TI - [Depressive reaction. Problems in classification, diagnosis and pathogenesis]. PMID- 1508229 TI - Leakage of carbonic anhydrase III from normal and denervated rat skeletal muscle following contractile activity. AB - Skeletal muscle extracellular carbonic anhydrase III was investigated in anesthetized rats by a microdialysis technique. A small dialysis probe was inserted into the tibialis anterior (TA) muscle and perfused continuously. Perfusates were collected before and during muscle contraction, induced by electrical stimulation of the muscle or of the sciatic nerve. In the perfusate of resting normal and denervated muscle, the concentration of CA III was 10 to 12 ng/mL, as measured by a radioimmunosorbent technique. During contractile activity, the concentrations of CA III increased markedly in the normal and denervated muscle. A TA muscle suspended in physiological saline behaved similarly, even though the leakage before and during contraction was higher than in vivo. The results show that skeletal muscle leaks CA III both in vivo and in vitro, a leakage which was markedly increased by contractile activity. The microdialysis technique should also be useful in humans to study the efflux of various proteins from different kinds of diseased or fatigued muscles. PMID- 1508230 TI - Single motor unit H-reflex in motor neuron disorders. AB - The latency fluctuation of single motor unit potentials (MUPH) in the H-reflex is greater than the latency fluctuation of MUPs in the direct (MUPM) and recurrent (MUPF) responses. This has been attributed to the variability in the impulse generation at the site of nerve stimulation, and to the variation in the synaptic delay at the anterior horn cell. We studied the latency fluctuation of single motor unit H-reflex in patients with motor neuron disorders (MND) in comparison with normal subjects. The mean jitter of the H-reflex was 264.3 +/- 17.8 microseconds (mean +/- SEM) in 30 MUPH recorded from 10 patients with ALS, 302.7 +/- 25.2 microseconds in 16 MUPH from 6 patients with chronic motor neuron diseases, as compared with 137.4 +/- 7.3 microseconds in 34 MUPH recorded from 10 normal subjects. This difference, which persisted even after the correction for the latency variation of MUPM, cannot be explained on the basis of an enhanced reciprocal inhibition. Thus, the increased latency fluctuation of the single motor unit H-reflex in patients with MND may reflect changes in the motoneuron pool excitability that may be secondary to altered intrinsic electrophysiological properties of motoneurons, or to an abnormal temporal and spatial summation of synaptic inputs on motoneurons. PMID- 1508231 TI - Beneficial effects of training on developing dystrophic muscle. AB - The objective of this study was to determine whether increased contractile activity is beneficial or detrimental to developing dystrophic muscle. Hamsters (20-days-old) were gradually introduced to running at a speed of 14 m/min at 10% grade for 2 (T2) or 4 (T4) h/d for 4 weeks, 5 d/wk. Histological and fiber type properties were determined in the soleus (SOL), plantaris (PL), and extensor digitorum longus and contractile properties in SOL and PL from 5 animals/group, including 5 controls. Experimental animals had normal body and muscle mass. Training for 2 h/d had little effect on SOL contractile properties, whereas 4 h/d resulted in significant increases in force, percentage of type I fibers, and type I hypertrophy. Force also increased in PL. Muscle necrosis was reduced in SOL (T2 and T4) and unchanged in PL. In conclusion, endurance training generally had a beneficial or, at least, no detrimental effect on developing dystrophic muscles. PMID- 1508232 TI - Needle electromyography of the diaphragm. AB - A method is described for performing needle electromyography of the diaphragm which is safe and causes little discomfort. It provides valuable information concerning neuropathies and myopathies which may affect the diaphragm, and complements information derived from phrenic nerve conduction studies. Firing patterns of motor unit potentials during spontaneous respiration identify upper motor neurone disorders causing respiratory insufficiency. PMID- 1508233 TI - Neuromuscular causes of prolonged ventilator dependency. AB - We prospectively evaluated 21 patients with prolonged ventilator dependency, to determine the frequency of unsuspected neuromuscular disease as a cause of this condition, and to determine the types of such diseases. Assessment was performed with routine and specialized electrophysiologic procedures. None of the patients had known prior neuromuscular disease, and none had ongoing medical problems that could account for their continued ventilator dependency. Sixty-two percent were found to have a neuromuscular disease severe enough to account for the ventilator dependency. Most of the remaining cases had a contributory neuromuscular disease. In addition to critical illness polyneuropathy, several other significant categories were identified. Myopathic EMG changes were found in 50% of the subgroup assessed by quantitative EMG. We conclude that neuromuscular disease is the most important factor in prolonged ventilator dependency, and that diseases other than critical illness polyneuropathy represent an important cause of this syndrome. PMID- 1508234 TI - Reciprocal changes in myosin isoform mRNAs of rabbit skeletal muscle in response to the initiation and cessation of chronic electrical stimulation. AB - Changes in myosin heavy chain (MHC) mRNAs were studied in rabbit fast-twitch muscles during continuous electrical stimulation at 10 Hz for periods up to 3 weeks, and during the first 12 days of the recovery process that followed cessation of 6 weeks' stimulation. Two cDNA probes were used to detect MHC mRNAs specific to fast- and slow-twitch skeletal muscle in RNase protection assays and Northern- and slot-blot analyses. The isolation and base sequence of one of these probes, corresponding to the MHC gene expressed in soleus (slow-twitch), is described. At an early stage of the response to stimulation, fast MHC mRNA was replaced by slow MHC mRNA. During recovery, this process occurred in reverse but took longer. The time course of recovery was slightly faster in tibialis anterior than in extensor digitorum longus. The changes in mRNAs during both stimulation and recovery reflected changes in the corresponding muscle proteins. PMID- 1508235 TI - Localization of nerve depolarization with magnetic stimulation. AB - The specific location on the magnetic stimulation (MS) coil that may correspond to the area of nerve depolarization has not been determined. In order to localize such an area, MS with 9-cm and 5-cm diameter coils was compared with conventional percutaneous electric stimulation (ES). On the 9-cm coil the distribution of points of nerve depolarization corresponded to that quarter of the coil which was placed over and parallel to the median nerve, whereas on the 5-cm coil, this area also extended outside the coil. The points of median nerve depolarization with MS were distributed over a distance of 7 cm on the stimulator head and was nearly identical for the 2 coil sizes at the wrist and elbow. Ulnar nerve costimulation was less frequent with the smaller coil at the wrist. A calculated reference point on the coil is suggested for more accurate NCV determinations. PMID- 1508236 TI - Changes in mast-cell distribution in skeletal muscle after denervation. AB - Motor nerves are known to govern the structure of skeletal muscle. In the normal guinea pig diaphragmatic muscle, we found that mast cells were predominantly located in the central tendon. Following denervation, these cells became more numerous in the muscle itself than in the tendon. Therefore, nervous trophic influences are exerted on other tissue elements besides those which sustain transmission and contraction. Ascertaining mast-cell distribution in biopsies may help to elucidate denervation effects in motor neuron disease. PMID- 1508237 TI - Cutaneous reflexes in Parkinson's disease. AB - The physiology of rigidity in Parkinson's disease (PD) can be investigated by the study of reflexes. Cutaneous reflexes (CR) were measured in 10 patients with PD and in 10 age- and sex-matched normal volunteers. EMG activity was recorded from the first dorsal interosseous muscle with surface electrodes, rectified and averaged. The index finger was stimulated with an intensity four times the sensory threshold. The subjects abducted the index finger with 20% of maximal force. While the latencies of the different reflex components and the amplitudes of the excitatory peaks were not different in the two groups, the first inhibitory component was less pronounced in patients with PD as compared with normals. This effect is partially reversed with dopaminergic drug treatment. The results are compatible with the loss of an inhibitory spinal mechanism elicited by cutaneous afferents, and can be a partial explanation for increased tone in PD. PMID- 1508238 TI - Dominantly inherited malignant hyperthermia (MH) in the King-Denborough syndrome. AB - A 14-year-old boy, an only child, with the phenotypical dysmorphic features of the King-Denborough Syndrome developed a severe hyperthermic episode during anesthesia which responded to the administration of sodium dantrolene. As adequate metabolic studies were not available at the time of the crisis he was referred for confirmation of the malignant hyperthermia (MH) status. Muscle tension studies confirmed the presence of MH. The patient's mother and father were subsequently tested and the mother was found to be MH positive, the father MH negative. PMID- 1508239 TI - Polyneuritis with granulomatous features: possible restricted expression of sarcoidosis. PMID- 1508240 TI - Deep peroneal sensory neuropathy. PMID- 1508241 TI - Genetic influence on smoking--a study of male twins. AB - BACKGROUND: The results of twin and family studies suggest that heredity has a small influence on smoking behavior. METHODS: We conducted a genetic analysis of several aspects of smoking behavior among subjects in the National Academy of Sciences-National Research Council Twin Registry. The registry includes male twins who were born in the United States between 1917 and 1927 and who were members of the armed services during World War II. Information on smoking history was available for 4775 pairs of twins, who were first surveyed in 1967 through 1969, when they were 40 to 50 years old, and then re-surveyed in 1983 through 1985, when they were 56 to 66. Eighty percent of the subjects in this cohort had smoked at some time in their lives, 60 percent were smokers in 1967 through 1969, and 39 percent were smoking in 1983 through 1985. Similarities between twins in smoking habits at base line and at the second follow-up 16 years later were examined. The comparison of concordance for smoking between monozygotic and dizygotic twins was used to assess the relative contribution of familial and genetic factors. RESULTS: In 1967-1969 survey the ratio of observed to expected concordance for smoking was higher among the monozygotic twins than among the dizygotic twins for those who had never smoked (overall rate ratio, 1.38; 95 percent confidence interval, 1.25 to 1.54), for former smokers (overall rate ratio, 1.59; 95 percent confidence interval, 1.35 to 1.85), for current cigarette smokers (overall rate ratio, 1.18; 95 percent confidence interval, 1.11 to 1.26), and for current cigar or pipe smokers (overall rate ratio, 1.60; 95 percent confidence interval, 1.22 to 2.06). The data also suggest genetic influences on quitting smoking. Monozygotic twins were more likely than dizygotic twins to be concordant for quitting smoking (overall rate ratio, 1.24; 95 percent confidence interval, 1.06 to 1.45). CONCLUSIONS: In this cohort of adult male twins, there were moderate genetic influences on lifetime smoking practices. PMID- 1508242 TI - Survival of nationally shared, HLA-matched kidney transplants from cadaveric donors. The UNOS Scientific Renal Transplant Registry. AB - BACKGROUND: The importance of HLA histocompatibility typing to the outcome of transplantation of cadaveric kidneys has been controversial. Four years ago, a prospective trial began in all U.S. transplantation centers to determine whether the results of transplantation would improve with the nationwide shipment of kidneys from cadaveric donors to waiting patients undergoing dialysis when there was a match at the HLA-A, B, and DR loci. METHODS: A total of 1386 cadaveric kidneys were shipped from 108 organ centers to 198 transplantation centers and distributed among HLA-matched recipients, 1004 of whom were receiving a first transplant and 382 of whom were receiving a subsequent transplant. Graft survival in these recipients was compared with that in 22,188 recipients of first transplants and 3950 recipients of subsequent transplants whose HLA antigens differed from those of the donor. RESULTS: The rate of graft survival at one year in recipients of HLA-matched first transplants was 88 percent, as compared with 79 percent in the recipients of mismatched grafts (P less than 0.001). The estimated half-life of the kidney after the first year was 17.3 years for matched grafts, as compared with 7.8 years for mismatched grafts (P = 0.003). Among paired kidneys from 470 donors, one-year graft survival was 87 percent in the recipients of matched first grafts, as compared with 80 percent in the recipients of the contralateral kidneys, who did not have HLA matches with the donors. In donors and recipients matched for the more highly defined split Class I and Class II HLA antigens, the rate of graft survival after one year was as high as 90 percent. CONCLUSIONS: The collaborative renal-transplantation program for HLA matching of donors and recipients yielded an increased rate of one-year graft survival and an estimated half-life for matched grafts twice that for mismatched grafts. An increased role for HLA matching in kidney allocation is therefore indicated. PMID- 1508243 TI - Racial differences in the survival of cadaveric renal allografts. Overriding effects of HLA matching and socioeconomic factors. AB - BACKGROUND: The long-term survival of cadaveric renal allografts is lower in black recipients than in white recipients, although the one-year graft survival is similar in these racial groups. We sought to determine what factors account for this disparity. METHODS: We studied 100 consecutive recipients of primary cadaveric renal allografts (57 were black and 43 white) at least 1 year after transplantation (mean, 40 months); all had received identical immunosuppressive therapy. We evaluated differences in the cause and duration of end-stage renal disease, the number of pretransplantation transfusions, age, matching for HLA-A, B, and DR antigens, race of the donor, insurance coverage, and compliance to assess their effect on graft survival in both groups. RESULTS: Allograft survival after one year was significantly lower in black than in white patients (P = 0.025). According to univariate analysis, only the recipient's age at transplantation, the number of mismatches for HLA antigens, the type of insurance coverage, the source of referral for transplantation, and the degree of compliance correlated significantly with the rate of graft survival. The frequency of all variables that reduced graft survival was higher among the blacks. According to proportional-hazards analysis, the only factors contributing to a lower rate of graft survival were age of less than 30 years at transplantation (relative risk, 2.3; 95 percent confidence interval, 1.3 to 4.6), mismatches for all six HLA antigens as compared with three or fewer mismatches (relative risk, 5.6; 95 percent confidence interval, 3.3 to 9.6), and coverage by Medicaid or Medicare (relative risk, 2.2; 95 percent confidence interval, 1.5 to 3.2). Race had no additional effect. Noncompliance was more frequent among blacks (16 percent vs. 2 percent) and could substitute for insurance status in the model. CONCLUSIONS: When immunosuppression is equivalent in black and white transplant recipients, apparently race-related differences in the long-term survival of renal cadaveric allografts appear to be related to other factors that affect graft survival unfavorably, notably poor HLA matching and unfavorable socioeconomic factors. PMID- 1508244 TI - The spectrum of symptoms and QT intervals in carriers of the gene for the long-QT syndrome. AB - BACKGROUND: The familial long-QT syndrome is characterized by a prolonged QT interval on the electrocardiogram, ventricular arrhythmias, and sudden death. It is not certain, however, that the length of the QT interval is a sensitive or a specific diagnostic criterion. Recently, we identified genetic markers on chromosome 11 that distinguished between carriers and noncarriers of the gene for the long-QT syndrome in three families. In this study, we compared the clinical features of carriers and noncarriers and assessed the diagnostic accuracy of the QT interval. METHODS: We obtained medical histories and electrocardiograms from 199 family members. QT intervals corrected for heart rate (QTc) were determined independently by two blinded investigators. Carriers of the long-QT gene (83 subjects) and noncarriers (116 subjects) were distinguished by genetic-linkage analysis. RESULTS: Fifty-two of the carriers of the long-QT gene (63 percent) had a history of syncope, whereas four (5 percent) had a history of aborted sudden death. The QTc intervals of the gene carriers ranged from 0.41 to 0.59 second (mean, 0.49). By contrast, the QTc intervals of the noncarriers ranged from 0.38 to 0.47 second (mean, 0.42). On average, carriers of the gene for the long-QT syndrome had longer QTc intervals than noncarriers, but there was substantial overlap (in 126 of the 199 subjects, or 63 percent). The use of a QTc interval above 0.44 second as a diagnostic criterion resulted in 22 misclassifications among the 199 family members (11 percent). QTc intervals of 0.47 second or longer in males and 0.48 second or longer in females were completely predictive but resulted in false negative diagnoses in 40 percent of the males and 20 percent of the females. CONCLUSIONS: In families affected by the long-QT syndrome, measurement of the QTc interval may not permit an accurate diagnosis. DNA markers make it possible to make a genetic diagnosis in some families, but not all gene carriers have symptoms. PMID- 1508245 TI - Brief report: treatment of insulin-resistant diabetic ketoacidosis with insulin like growth factor I in an adolescent with insulin-dependent diabetes. PMID- 1508247 TI - Bacterial meningitis: pathogenesis, pathophysiology, and progress. PMID- 1508248 TI - Case records of the Massachusetts General Hospital. Weekly clinicopathological exercises. Case 37-1992. A 68-year-old woman with rheumatoid arthritis and pulmonary hypertension. PMID- 1508246 TI - Risk factors for fatal residential fires. AB - BACKGROUND: Residential fires are the most important cause of fire-related mortality in the United States. Previous research has concentrated on fatal fires in urban areas; considerably less is known about fatal fires in rural areas. METHODS: We studied fatal and nonfatal residential fires in predominantly rural areas. Using a case-control design, we compared all 151 fatal fires (cases) in single-family dwellings in North Carolina during a 13-month period with a sample of nonfatal fires (controls). Case fires were identified through the medical examiner system, and control fires that occurred within a few weeks of the case fires were chosen from the records of randomly selected fire departments statewide. For each fire, fire officials were interviewed about the dwelling, the fire, the people involved, and the fire-response system. RESULTS: Although heating incidents were the leading cause of fires, fatal fires were more likely to have been caused by smoking (31 percent of fatal fires vs. 6 percent of nonfatal fires). Mobile homes posed a higher risk of death if a fire occurred (odds ratio, 1.7; 95 percent confidence interval, 1.1 to 2.6), as did the absence of a smoke detector (odds ratio, 3.4; 95 percent confidence interval, 2.1 to 5.6). Smoke detectors were more protective against death in fires involving young children and when no one present was impaired by alcohol or drugs or had a physical or mental disability. The presence of an alcohol-impaired person was the strongest independent risk factor for death in the case of a fire (odds ratio, 7.5; 95 percent confidence interval, 4.4 to 12.7). CONCLUSIONS: Residential fires are most likely to be caused by heating equipment or smoking materials. The risk of death is greatest in fires in mobile homes, in those involving alcohol impaired persons, and in those in houses without smoke detectors. PMID- 1508249 TI - The genetics of drug dependence: tobacco addiction. PMID- 1508250 TI - Every kidney counts. PMID- 1508251 TI - Molecular genetics and ventricular arrhythmias. PMID- 1508252 TI - What keeps the home fires burning? PMID- 1508253 TI - Anti-endotoxin monoclonal antibodies. PMID- 1508254 TI - Anti-endotoxin monoclonal antibodies. PMID- 1508255 TI - Anti-endotoxin monoclonal antibodies. PMID- 1508256 TI - Methotrexate for juvenile rheumatoid arthritis. PMID- 1508257 TI - Vitamin D content of infant formula. PMID- 1508258 TI - Hypertension and catecholamine biosynthesis associated with a glomus jugulare tumor. PMID- 1508259 TI - Clinical problem-solving: the landlady confirms the diagnosis. PMID- 1508260 TI - US politics: campaigns as usual. PMID- 1508261 TI - Rising toll from AIDS in Japan prompts big jump in spending. PMID- 1508262 TI - NSF's proposed conflict-of-interest rules place burden on applicant and institution. PMID- 1508263 TI - Court-appointed scientists provide technical expertise. PMID- 1508264 TI - Japanese open infectious disease lab despite local and national protests. PMID- 1508265 TI - Air pollutants and lung cancer. PMID- 1508266 TI - Cystic fibrosis. A welcome animal model. PMID- 1508267 TI - Developmental psychology. Arithmetic in the cradle. PMID- 1508268 TI - Alternative blood substitutes. PMID- 1508269 TI - Addition and subtraction by human infants. AB - Human infants can discriminate between different small numbers of items, and can determine numerical equivalence across perceptual modalities. This may indicate the possession of true numerical concepts. Alternatively, purely perceptual discriminations may underlie these abilities. This debate addresses the nature of subitization, the ability to quantify small numbers of items without conscious counting. Subitization may involve the holistic recognition of canonical perceptual patterns that do not reveal ordinal relationships between the numbers, or may instead be an iterative or 'counting' process that specifies these numerical relationships. Here I show that 5-month-old infants can calculate the results of simple arithmetical operations on small numbers of items. This indicates that infants possess true numerical concepts, and suggests that humans are innately endowed with arithmetical abilities. It also suggests that subitization is a process that encodes ordinal information, not a pattern recognition process yielding non-numerical percepts. PMID- 1508270 TI - A test of reciprocal X-Y interactions as a cause of hybrid sterility in Drosophila. AB - Elucidation of the nature of the gene interactions that underly the sterility of interspecific hybrids is important in evolutionary biology. The interactions between the heterospecific X and Y (or Z and W) chromosomes are often used as an explanation for two reasons. First, the fertility of the hybrids of the heterogametic sex is much more often affected than that of the homogametic sex (Haldane's rule) and X-Y interactions are specific to the heterogametic sex. Second, sex chromosomes, especially the X chromosome, are often considered to be of special importance in determining the fertility of hybrids. X-Y interactions have been addressed in studies of males with a heterospecific Y chromosome in a mixed genetic background. A more stringent test of the X-Y interaction model requires each X chromosome sterility factor to be tested separately for its interaction with the Y chromosome in a homogeneous background of the pure species. Here we report such a test of the X-Y interaction model and conclude that X-Y interactions should not be assumed to be the only or even the most common cause of hybrid sterility. PMID- 1508271 TI - Mixed parvocellular and magnocellular geniculate signals in visual area V4. AB - Visual information from the retina is transmitted to the cerebral cortex by way of the lateral geniculate nucleus (LGN) in the thalamus. In primates, most of the retinal ganglion cells that project to the LGN belong to one of two classes, P and M, whose axons terminate in the parvocellular or magnocellular subdivisions of the LGN. These cell classes give rise to two channels that have been distinguished anatomically, physiologically and behaviourally. The visual cortex also can be subdivided into two pathways, one specialized for motion processing and the other for colour and form information. Several lines of indirect evidence have suggested a close correspondence between the subcortical and cortical pathways, such that the M channel provides input to the motion pathway and the P channel drives the colour/form pathway. This hypothesis was tested directly by selectively inactivating either the magnocellular or parvocellular subdivision of the LGN and recording the effects on visual responses in the cortex. We have previously reported that, in accordance with the hypothesis, responses in the motion pathway in the cortex depend primarily on magnocellular LGN. We now report that in the colour/form pathway, visual responses depend on both P and M input. These results argue against a simple correspondence between the subcortical and cortical pathways. PMID- 1508272 TI - The structure of ribosomal protein S5 reveals sites of interaction with 16S rRNA. AB - Understanding the process whereby the ribosome translates the genetic code into protein molecules will ultimately require high-resolution structural information, and we report here the first crystal structure of a protein from the small ribosomal subunit. This protein, S5, has a molecular mass of 17,500 and is highly conserved in all lifeforms. The molecule contains two distinct alpha/beta domains that have structural similarities to several other proteins that are components of ribonucleoprotein complexes. Mutations in S5 result in several phenotypes which suggest that S5 may have a role in translational fidelity and translocation. These include ribosome ambiguity or ram, reversion from streptomycin dependence and resistance to spectinomycin. Also, a cold-sensitive, spectinomycin-resistant mutant of S5 has been identified which is defective in initiation. Here we show that these mutations map to two distinct regions of the molecule which seem to be sites of interaction with ribosomal RNA. A structure/function analysis of the molecule reveals discrepancies with current models of the 30S subunit. PMID- 1508273 TI - Health care reform begins at home. PMID- 1508274 TI - An interview with Angela Skalla and Luke McGuinness. Interview by Connie R. Curran. AB - The partnership between the chief executive officer and chief nurse officer is vital for driving quality improvement and delivering outstanding patient care while containing or reducing costs. These two leaders must create and communicate a vision statement to lead and build a strong management team. PMID- 1508275 TI - Restructuring nursing care delivery systems. AB - Job design and system redesign theory are applied to elucidate costs and benefits of alternative restructuring schemes. Strategies are outlined for nurse executives to use for successful reconceptualization of nursing positions. PMID- 1508276 TI - Unit-based clinical nurse specialist: redesigning nursing services. AB - At the Johns Hopkins Hospital, the Medical Nursing Services redesigned its delivery of direct patient care to include nurse managers, staff nurses, nursing support technicians, and unit-based clinical nurse specialists (CNSs). The CNS role proved efficacious to both nursing staff and nurse managers. PMID- 1508277 TI - Nursing challenges in managed care. AB - The emergence of managed care organizations offers many opportunities, challenges, and threats for nursing and nurses. The goal of these organizations (ensuring maximum value from resources used) is congruent with the basic philosophy of nursing, which focuses on the total needs of the patient, not just disease, and on maintaining the health of the individual to minimize the need for expensive health care services. Within the structure of managed care, however, there is also a need for strong professional advocacy to ensure that the needs of the members are adequately met as the organization strives to maintain costs. In meeting the needs of the organization and of the members, the nurse also plays an important role in managing the resources used in producing health care services. PMID- 1508278 TI - Nursing care costs for a DRG sub-group. AB - This study determined the average cost of nursing care for two DRGs and evaluated how a specific nursing intervention, Phase I Cardiac Rehabilitation, impacts on these costs. A unit-based methodology to determine the cost of providing nursing care to patients who stay on more than one nursing care unit during their hospital stay will facilitate decision making by nurse administrators and clinicians to contain rising health care costs. PMID- 1508280 TI - Improving automated care planning with plan libraries: a future use of technology in nursing. PMID- 1508279 TI - Power at meetings: strategies to move people. AB - Opportunities exist during meetings to become visible, make impressions, gain control, and be an initiator of decisions. Selective strategies and group dynamic skills enhance the nurse manager's ability to generate influence and power at meetings. PMID- 1508281 TI - Democratic reforms. PMID- 1508282 TI - Salarying of nursing staff. PMID- 1508283 TI - "Bite the bullet". PMID- 1508284 TI - They just ain't gettin' it. PMID- 1508285 TI - Use of electroneuronography in monitoring facial nerve paralysis. AB - FNP is a disease entity seen in a variety of clinical settings. We recommend early ENoG evaluation of every total facial nerve paralysis to assess the percentage of degeneration. ENoG is an objective, permanent record with prognostic significance especially in 16% of those patients who are predicted to have a poor outcome without further intervention. In consultation with the patient a treatment plan can thus be proposed to optimize the opportunity for recovery. PMID- 1508286 TI - A case report: shortness of breath and yellow nails. PMID- 1508287 TI - Sex steroid hormones in the pathogenesis of chronic subdural haematoma. AB - In order to verify whether hormonal factors could be involved in the pathogenesis of Chronic Subdural Haematoma (CSDH), based on clinical and epidemiological demonstration of higher incidence of this disease in male patients and particularly in those with high urinary estrogen values, Estradiol (ER) and Progesterone (PR) Receptors were studied in the Haematoma External Membrane (HEM) in 18 male and 7 female CSDH patients. The observed higher incidence of ER and PR in male rather than in female patients (73% vs 27% and 72% vs 28% for male and female patients respectively), and the higher concentration of ER in the HEM of male rather then female patients (55 +/- 15 S.E. vs 13 +/- 7 S.E. fmol/mg protein) suggest that this pathological process, which affects individuals whose gonadal activity is quiescent, is mainly dependent upon hormonal local effect played by estrogen compounds on the HEM of the male patients. In this sex, in fact, whose tissues are not usually adapted to an estrogen action, the effect of estrogens on a responsive tissue such as the newly-vascularized HEM could lead to an increased formation of tissue Plasminogen Activator (t-PA), a compound that, escaping into the subdural collection, could maintain a local hyperfibrinolysis with formation of Fibrinogen Degradation Products (FDP). Therefore local hyperfibrinolysis enhanced by steroid hormones and the subsequent CSDH may perhaps be influenced by the prophylactic or adjuvant treatment with inhibitors either of the aromatase activity or of the estrogen action at receptor level. PMID- 1508288 TI - Intracranial hydatid cysts: experience with surgical treatment in 120 patients. AB - Intracranial hydatid cysts, although rare, are still prevalent in agricultural and sheep-raising communities. The authors discuss some of the peculiarities in 120 consecutive cases of intracranial hydatid cysts and review the literature in this report. PMID- 1508289 TI - Gadolinium-DTPA enhancement of dural structures on MRI after surgery. AB - Gadolinium-DTPA enhanced MRI was examined before and after surgery in 14 patients with particular attention to the enhancement of falx cerebri, tentorium cerebelli and dura mater. A marked enhancement was observed in 2 falx and 2 tentorium before surgery, whereas it was observed in 7 falx, 9 tentorium and 11 dura after surgery. Among 6 falx, 7 tentorium and 12 dura showing increased enhancement after surgery, 2 falx, 3 tentorium and 8 dura showed marked enhancement which was not observed before surgery. A small amount of subdural haemorrhage during surgery is known to heal as subdural neomembrane with capillaries. An increased enhancement of dural structures conceivably derives from the extravasation of Gd DTPA through capillaries involved in the subdural neomembrane. In the postoperative MRI, the enhancement of dural structures should be taken into consideration. PMID- 1508290 TI - Metallic fragment embolization to the middle cerebral artery. AB - A 25-year-old male was wounded accidentally in the neck by a metallic fragment, which penetrated his right carotid artery and migrated within the ipsilateral middle cerebral artery. Clinical and laboratory findings over a 16-month-period are reported. Problems arising from the presence of metallic emboli to the cerebral circulation are discussed on the basis of the pertinent literature. PMID- 1508291 TI - Extrusion of peritoneal catheter through a thoracic skin fistula: report of a rare complication of ventriculoperitoneal shunt. AB - A very rare complication of ventriculoperitoneal shunt is presented. The tip of the distal catheter extruded through a skin fistula in the right subclavian region. After the replacement of a new catheter in the peritoneal cavity, inflammation of the overlying scar occurred. Then, a ventriculoatrial shunt was carried out. The authors suggest a possible mechanism of this complication. PMID- 1508292 TI - Fibrous dysplasia of the cervical spine with atlanto-axial dislocation. AB - We report on a case of fibrous dysplasia of the cervical spine accompanied by atlanto-axial dislocation, a rare condition first reported by Stirrat. A 37-year old man who had shown cervical myelopathy for about 6 months was diagnosed as having cervical fibrous dysplasia on the basis of plain x-ray and CT film findings. In addition, atlanto-axial dislocation, which was the apparent main cause of his symptoms, was also detected. We performed a successful two-stage operation from first the posterior and then the anterior approach. The possibility that grafted cancellous bone for anterior fusion may be replaced by dysraphic tissue in the presence of fibrous dysplasia was a complicating factor in this case. PMID- 1508293 TI - Convexity meningioma associated with empty sella presenting as primary amenorrhea. AB - A case of a 30-year-old female seen for a convexity meningioma is presented. History and investigations revealed an empty sella turcica associated with primary amenorrhea. The removal of the convexity meningioma resulted in the disappearance of the amenorrhea and in the rise of plasma gonadotropins. The importance of the consideration of intracranial causes in patients who have a delayed puberty or the absence of a menstrual history is briefly emphasized in the light of literature. PMID- 1508294 TI - Vasospasm after experimentally induced subarachnoid haemorrhage and treatment with nimodipine. AB - At day one and on the following day subarachnoid haemorrhage (SAH) was induced in SPF-rats by injection of a mixture of autologous blood and CSF into the cisterna magna. At day eight the animals were treated with Nimodipine. Extracellular calcium and -potassium concentrations as well as local cerebral blood flow and arterial blood pressure were measured simultaneously. The cerebral vasospasm was documented by corrosion casts. The control group underwent the same procedure without previous SAH. Cerebral vasospasm still exists after nimodipine infusion as it can be demonstrated by corrosion casts showing an intensive grooving and a vertical relief. Extracellular potassium and calcium concentration are higher in the SAH-group than in the control-group. The influence of nimodipine to blood pressure and cerebral blood flow is more impressive in rats with SAH showing a significant decrease in blood pressure and local blood flow. PMID- 1508295 TI - Acetylcholinesterase-rich pyramidal neurons in Alzheimer's disease. AB - The distribution of acetylcholinesterase (AChE)-rich pyramidal neurons was studied in the cortices of 7 Alzheimer's Disease (AD) patients and 4 normal-aged subjects. Both groups showed a characteristic distribution of these neurons with the highest density in motor and premotor areas, moderate density in association cortices, and low density in limbic-paralimbic areas. Three areas (Brodmann areas 6,22, and 24) were chosen for quantitative analysis. The number of pyramidal neurons that display an AChE-rich staining pattern was significantly reduced in AD patients. Nerve cell density was not significantly different in adjacent Nissl stained sections. The density of AChE-rich (cholinergic) fibers was also decreased in all three cortical areas of the AD patients but was not correlated with the number of AChE-rich neurons. Loss of AChE-rich neurons was more pronounced in areas with high counts of tangles. These findings show that layer 3 and 5 pyramidal neurons in AD display a reduction of AChE activity. This phenomenon can not be attributed to the well known loss of cortical neurons or cholinergic innervation in AD. PMID- 1508296 TI - Cell loss in the nucleus raphes dorsalis in Alzheimer's disease. AB - Marked neuron loss in the predominantly serotonergic nucleus raphes dorsalis (NRd) in Alzheimer's disease (AD) has repeatedly been reported in the literature. However, most of these studies quantitated only part of the NRd and data were expressed as numerical density. Applying a 3-dimensional sampling scheme throughout the entire rostrocaudal extent of the NRd and sampling neurons regardless of their size and staining characteristics, an overall neuron loss of 39.4% was demonstrated and a tendency for cell shrinkage was likely to be present. No rostrocaudal gradient in neuron loss could be shown. These NRd data are in accordance with neuron loss in other subcortical structures in AD. PMID- 1508297 TI - Olfactory bulb lesions in Alzheimer's disease. AB - The olfactory bulb (OB), with its comparatively simple and well-delineated connectivity, presents an interesting system for examining cell-specific pathology in neurologic degenerative disorders such as Alzheimer's disease (AD). We have found that in AD the large, efferently projecting neurons (mitral cells) of the OB degenerate, typically without classical Alzheimer neurofibrillary changes. In some cases, with less severe neocortical pathology, the terminal arborizations of olfactory nerve appear hyperplastic and are associated with focal accumulations of A-4 (beta-amyloid) immunoreactivity that are not detectable by standard amyloid stains. These abnormalities may represent a pathologic manifestation of normally occurring plasticity in the olfactory system. PMID- 1508298 TI - Impaired acquisition of novel locomotor tasks in aged and norepinephrine-depleted F344 rats. AB - Performance of rats on a motor learning paradigm that has been demonstrated to be dependent upon cerebellar norepinephrine (NE) was studied in 20-month-old F344 rats. The behavioral task is identical to that described by Watson and McElligott: Rats are trained on a runway consisting of aluminum pegs arranged in a regular pattern. Rats receive a water reward at either end of the runway. Subsequent to training, rats are tested for running times on a runway with irregularly spaced rods. The ability of rats to improve their performance (decrease their running times) on this novel motor task is diminished in young rats that have received 6-hydroxydopamine lesions. Rats at 20 months of age are known to have deficits in cerebellar noradrenergic transmission; thus, the hypothesis to be tested was to determine if aged rats demonstrated performance deficits similar to young rats depleted of central stores of NE. The rate of acquisition of the task was determined by the decrease in running times with successive days of training. The ability of 20-month-old F344 rats to acquire proficiency on the novel motor task was impaired and the rate of acquisition of the novel motor task was not different from the young 6-hydroxydopamine-lesioned rats. In an attempt to distinguish between alterations in motor coordination and motor learning, additional tests of psychomotor performance were assessed for all groups of rats. These tests included a walking on 2.5- and 5-cm rods, speed of running on the motor task, and number and types of mistakes made on the motor learning task.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1508299 TI - Reduced temporal lobe blood flow in Alzheimer's disease. AB - We used single photon emission computed tomography with the blood flow tracer [123I]N-isopropyl-p-iodoamphetamine (IMP) to study regional cerebral blood flow (rCBF) in 50 mildly and moderately demented Alzheimer's disease (AD) patients to evaluate rCBF as a function of disease severity. Relative rCBF (normalized to occipital cortex) was significantly lower than controls in temporal cortex for both mildly and moderately demented patients. Similar numbers of patients in both groups demonstrated perfusion abnormalities in temporal neocortex. Parietal cortex was more variably involved with greater numbers of moderately than mildly demented patients showing perfusion abnormalities. Relative rCBF in dirsolateral frontal cortex was reduced only in the moderately demented patients. Disease severity, as measured by the Mini Mental Status Examination, was associated with relative rCBF only in dorsolateral frontal and parietal cortex. These results suggest that the temporal lobes are the first neocortical regions affected by AD and that other cortical areas become involved as the disease progresses. PMID- 1508300 TI - Changes in intraneuronal lipopigment in Alzheimer's disease. AB - Brains were examined from 22 patients with Alzheimer's disease (AD) (mean age 80.5, S.D. 11.5) and were compared with brains from 20 nondiseased subjects (mean age 81.1, S.D. 10.2). Intraneuronal lipopigment in all layers of a region of the superior frontal cortex was identified by fluorescence microscopy. The areas enclosed by the outlines of discrete regions of lipopigment autofluorescence were measured and assigned to a range of size categories. AD was associated with significant (p less than 0.05) decreases in the mean number (per neuron) of discrete regions of yellow lipopigment autofluorescence in the three smallest size categories and a significant increase in one of the larger size categories. Also, AD was associated with a significant decrease in the mean number (per neuron) of discrete regions of lipopigment autofluorescence (p less than 0.001). Significant (p less than 0.05) correlations were obtained between the Blessed dementia score (obtained within 2 years of death) and these lipopigment variables. The changes in neuronal lipopigment in AD may reflect an increased rate of lipopigment formation related to membrane and lysosomal abnormalities. PMID- 1508301 TI - Age-related changes in sulfide-silver staining in the rat neostriatum: a quantitative histochemical study. AB - The density and distribution of sulfide-silver staining in the neostriatum of 3-, 12-, and 24-month-old male Sprague-Dawley rats were analyzed using the neo-Timm sulfide-silver histochemical technique associated with microdensitometry. This technique stains zinc-containing terminals in the striatum and the density of neo Timm staining is considered to be parallel to the density of synaptic boutons containing zinc. In the neostriatum sulfide-silver, staining was intense in the matrix, although the striosomes did not show appreciable reactivity. The density of sulfide-silver staining was significantly reduced (p less than 0.001) in the matrix of 12-month-old in comparison to 3-month-old rats. No further changes were noticeable between 24- and 12-month-old rats. In contrast, the area and the perimeter of neostriatum that were assessed by quantitative image analysis did not show age-related changes. The present results indicated that similar to the observations for a variety of neurochemical parameters of rat neostriatum such as local cerebral glucose utilization, cholinergic muscarinic receptors, and dopamine D-1 receptors, zinc-containing striatal terminal were primarily decreased between young and adult subjects but not between adult and aged animals. PMID- 1508302 TI - Decreased carbachol-stimulated inositol 1,3,4,5-tetrakisphosphate formation in senescent rat cerebral cortical slices. AB - It is well established that muscarinic cholinergic receptors are linked to phosphoinositide hydrolysis in brain. Previous studies of muscarinic responses used Li+ to increase inositol phosphate accumulation and suggested little or no change during aging. Li+ disrupts certain aspects of the inositol phosphate metabolism and inhibits the formation of inositol 1,3,4,5-tetrakisphosphate [Ins(1,3,4,5)P4]. Ins(1,3,4,5)P4 appears to have second messenger functions. To investigate the effects of aging on agonist stimulated Ins(1,3,4,5)P4 formation, young (6-8 months) and old (28-30 months) Fischer 344 rat cerebral cortical or hippocampal slices were challenged with various agonists known to stimulate phosphoinositide hydrolysis in brain using a recently developed assay that does not use Li+. Carbachol and quisqualate stimulated [3H]inositol trisphosphate ([3H]InsP3) and [3H]Ins(1,3,4,5)P4 formation in young and old rat cerebral cortical slices. Norepinephrine, 5-hydroxytryptamine, and vasopressin failed to stimulate [3H]Ins(1,3,4,5)P4 or [3H]InsP3 formation in either young or old rat cerebral cortical slices. In old rat cerebral cortical slices, the carbachol stimulated [3H]Ins(1,3,4,5)P4 formation was reduced by 44%. Angiotensin II stimulated [3H]InsP3 was increased (219%) in old rats. There was no influence of aging either on the basal level or on the maximal response to carbachol or quisqualate in hippocampal slices. These studies suggest region-specific changes in phosphoinositide hydrolysis during aging. PMID- 1508303 TI - Analysis of Con A-binding glycoproteins in synaptosomal membranes. AB - Concanavalin A (Con A)-binding proteins obtained from solubilized synaptosomal membranes of bovine brain were analyzed by two-dimensional electrophoresis (2DE), and were identified by peroxidase conjugated Con A (Con A-peroxidase staining), after transfer from 2DE gel to nitrocellulose paper. The Con A-binding proteins were resolved up to 40 spots, ranging in isoelectric points (pI) from 4.5 to 8.0 and molecular weight (MW) from 10 kDa to 120 kDa. Most of the Con A-binding proteins were streaked across a pH gradient and/or exhibited as multiple spots, indicating broad charge and molecular weight heterogeneity. The presence of protein groups that showed high affinities for Con A were revealed. Most interesting group (named GP51), which consisted of seven spots separated horizontally in charge heterogeneity (pI5.85-7.5) with MW 51 kDa, was characterized by its binding to an immobilized protein A gel. This implies that GP51 is related to immunoglobulins and/or GP51 may be a new member of the immunoglobulin supergene family. PMID- 1508304 TI - Microcephalic cerebrum with hypomyelination in the congenital goiter mouse (cog). AB - 2',3'-Cyclic nucleotide 3'-phosphohydrolase activity in the cerebrum of the congenital goiter mouse (cog/cog) is reduced in comparison with the normal heterozygote (cog/+). The weight of the cog/cog cerebrum and cerebellum were significantly less than those of the normal controls, 89.0% less for the cerebrum, and 81.1% less for the cerebellum. However, no differences were observed with regard to DNA and RNA content and the RNA/DNA ratio. The results of this study indicate that hypomyelination in the congenital goiter mouse is restricted to the cerebrum, and is not related to arrested glial proliferation. PMID- 1508305 TI - A factor derived from chick embryo retina which inhibits DNA synthesis of retina itself. AB - Chick embryo retinas contain a peptide factor that inhibits DNA synthesis in explants of chick embryo retina. The inhibitory factor, obtained by acid/ethanol extraction from 15-day-old chick embryo retinas, was partially purified by affinity chromatography on heparin-sepharose CL-6B and gel filtration on Sephadex G-100. The inhibitor reduced DNA synthesis with maximal effects observed in retinal explants from 7 to 8-day-old chick embryos. The inhibitory effect became apparent after 10 h of incubation and reached the maximum levels after 16 h. DNA inhibiting activity was heat and acid-stable and was destroyed by trypsin and alkaline treatments. The inhibitory effect was observed in retinal explants incubated in a medium free from L-glutamine, and the addition of this compound to the medium reduced the inhibitory effect in a concentration-dependent manner. PMID- 1508306 TI - The susceptibility of MAP-2 to proteolytic degradation increases when bound to tubulin. AB - During experiments studying dietary effects on phosphorylation/dephosphorylation of MAP-2 we found that incubation of microtubules with alkaline phosphatase resulted in extensive proteolysis of MAP-2 but not of tubulin or Tau proteins. In the absence of tubulin, when microtubule-associated proteins (MAPs) were incubated with alkaline phosphatase, MAP-2 was not proteolyzed. This suggests that binding to tubulin induces a conformational change in MAP-2 which makes it more susceptible to proteolysis. The proteolysis of MAP-2 by alkaline phosphatase was prevented by inhibitors of serine proteases, suggesting that the commercial preparation of the enzyme is contaminated by a serine protease and/or that the enzyme also has a weaker proteolytic activity. In addition, selective proteolysis of MAP-2 can be obtained with the metalloprotease collagenase. Brain homogenates are shown to contain a Ca(2+)-dependent protease which selectively degrades MAP-2 bound to tubulin. These results suggest that selective proteolysis of tubulin bound MAP-2 could play a role in the regulation of microtubule dynamics in response to extracellular signals. PMID- 1508307 TI - Regional alterations in brain amino acids during the estrous cycle of the rat. AB - Concentrations of 11 amino acids, including the neurotransmitters GABA, glutamate, aspartate, glycine and taurine, were determined in 12 brain regions of female rats during different stages of the estrous cycle. In addition, amino acids and sex hormone levels were determined in plasma. All sample collections were done in the forenoon between 9 and 11 a.m. Most regional amino acid levels measured did not change significantly during estrous cycle, but significant alterations were found for GABA and glutamate in hypothalamus. Both amino acids were slightly decreased in hypothalamus during proestrus, which might reflect an alteration of GABA turnover in response to the high estrogen levels during this stage. A decreased glutamate level during proestrus was also found in thalamus, while both glutamate and GABA did not vary throughout estrous cycle in any of the other examined regions, including substantia nigra, amygdala, striatum, cortex and hippocampus. When diestrus was subdivided according to progesterone levels, high levels of this hormone seemed to be associated with effects on metabolism of certain amino acids, including glycine in substantia nigra, alanine in thalamus and threonine in pons/medulla. However, the few changes in regional amino acid concentrations found during the estrous cycle were so small that the functional significance of these changes cannot be ascertained without further determination of the cellular or subcellular compartments of brain tissue involved. PMID- 1508308 TI - Ventricular injection of nerve growth factor increases dopamine content in the striata of MPTP-treated mice. AB - Experimental depletion of dopaminergic striatal neurons was induced in mice with the neurotoxin MPTP. To investigate a possible effect of nerve growth factor on the damaged neurons, we injected 4 micrograms into the right cerebral ventricle of mice three days after the last administration of MPTP. We found a significant increase of dopamine and homovanillic acid in the striatum of MPTP treated mice after NGF administration when compared with dopamine and HVA levels in MPTP treated control mice (p less than 0.001). The increase of dopamine and homovanillic acid seems to be related to a partial restorative effect of NGF on the damaged dopaminergic cells, since ventricular administration of NGF to normal mice did not increase dopamine or homovanillic acid contents above the levels measured in untreated controls. It appears that administration of nerve growth factor produces a beneficial effect on damaged dopaminergic neurons; this effect could be due to stimulation of neuron sprouting from neurons that survived the toxic effect of MPTP. The increase of dopamine levels was seen 8 days after injection of nerve growth factor and was maintained at least until day 25, showing a lasting persistence of the restorative effect. PMID- 1508309 TI - [3H]serotonin binding sites in goldfish retinal membranes. AB - Serotonin (5HT) binding sites were studied in goldfish retinal membranes by radioligand experiments. The binding site of [3H]5HT was sensitive to pre treatment of the membranes at 40 degrees or 60 degrees C. 5HT and 5-methoxy-N,N dimethyltryptamine were the best inhibitors of [3H]5HT binding to retinal membranes. The 5HT2 agonist, 1-(-naphthyl)piperazine, was also a potent inhibitor, however, (+)-1-2,5-dimethoxy-4-iodophenyl-2-aminopropane was less efficient. The catecholaminergic agents haloperidol and clonidine did not display an important inhibition. Propranolol, also reported as 5HT1B antagonist, was a relatively potent blocker. Monoamine uptake blockers did not show potent inhibition. The GTP analog, GppNHp, inhibited the binding. The iterative analysis of saturation curves revealed two classes of binding sites, a high affinity component (B(max) 2.45 pmol/mg of protein, kd 6.86 nM), and a low affinity component (B(max) 53.46 pmol/mg of protein, Kd 232.07 nM). Analysis of the association and dissociation kinetics suggested a binding site (Kd 2 nM). The semilogarithmic plot of the dissociation kinetics gave curves concave to the upper side. The selectivity of the binding and the inhibition by GppNHp suggest the existence of 5HT1 receptors in goldfish retina. The low affinity interaction probably represents the transporter of 5HT or a subtype of receptor expressed in glial cells. PMID- 1508310 TI - [A combined anterior and lateral approach for cervical spondylosis; trans-unco discal approach (TUD method)]. PMID- 1508311 TI - [Experience with BALT magic catheter (PURSIL catheter); especially investigation about advantage, disadvantage and the applications]. AB - BALT magic catheter (PURSIL catheter) is a new catheter which is more flexible and plaint than the TRACKER-18 catheter because its mid-section and distal portion are made from polyurethane and silicon rather than polyethylene. Because the PURSIL catheter is flexible, it cannot be inserted with a guide wire, although it can be inserted into circulation during injection of contrast medium. Its inner diameter, 3.5mm, is smaller than that (5mm) of the TRACKER. There are few reports of embolization with the PURSIL catheter, and these describe only embolization using adhesive liquid embolus material. Embolization using small particles through the PURSIL catheter has never been reported. We report the catheterization using the PURSIL catheter of 26 arteries in 15 patients. The catheter was used for superselective angiography to clarify feeder and amytal tests in 5 patients with AVM, and embolization using PVA particles (150-250 microns) was performed in 1 patient with AVM, 3 patients with dural AVM, 4 cases with meningioma and 1 patient with vertebral aneurysm. Small PVA particles were easily injected without resistance through this catheter. In only one patient with dural AVM, was catheterization with this catheter not successful, and that was because the distal portion of the internal maxillar artery was extremely tortuous because of severe atherosclerosis. No complications associated with the use of this catheter were observed. We think that the greatest advantage of this catheter is the safety afforded by not using a guide wire. A disadvantage of this catheter is that, because of its small inner diameter, only small particles, or liquid embolus material can be injected through it.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1508312 TI - [Inhibition of c-sis protein synthesis and cell growth with antisense oligonucleotides in human glioma cells]. AB - The protein encoded by the proto-oncogene c-sis is over-amplified in human neuroglial tumors and has been hypothesized as playing an important role in tumorigenesis, but this hypothesis remains to be clarified. In order to address this issue, we examined the effect of 18-bp oligodeoxynucleotides complementary to the sense mRNA of c-sis upon glioma cell growth. First, we investigated the expression of c-sis protooncogenes within cultured human glioma cell lines and also fresh glioma specimens by using polymerase chain reaction. We could detect mRNA transcripts of c-sis in 3 out of 4 glioma cell lines (U138MG, U251MG and A172) and two in 5 glioblastoma multiforme specimens. The antisense oligonucleotides complementary to c-sis mRNA were efficiently incorporated into A172 in vitro and the kinetic study showed that maximum uptake occurred after 48 hours of incubation with antisense oligomers. Exposure of human glioma cell lines to antisense oligodeoxynucleotides targeted against first initiation codon inhibited cell proliferation in a time and dose dependent fashion. From the flow cytometric analysis using anti-c-sis sera, it was demonstrated that the antisense oligomers specifically block the de novo synthesis of intracellular c-sis protein by glioma cells dose-dependently. In contrast to this, the corresponding sense oligomers inhibited neither synthesis of c-sis protein nor glioma cell growth. Taken together, these results clearly support a role of c-sis protein in the proliferation process and show that inducible protein expression can be blocked by means of synthetic oligonucleotides complementary to a coding exon. PMID- 1508313 TI - [Experimental study of aneurysmal occlusion with fibrin glue]. AB - The authors report an experimental trial of intra-aneurysmal occlusion using fibrin glue. Nowadays, with the development of microsurgical techniques and aneurysmal clips, results of direct radical operations have been improving. But quite a few aneurysms cannot be clipped because of their size, location, broad neck etc. Some authors have treated these aneurysms with innovative techniques (detachable balloon techniques etc). In these methods, the occlusive state of the aneurysms is not always obtainable because of the size of their neck. Besides, it is not always possible to preserve the parent arteries of the aneurysms. Experimental aneurysms in cervical carotid arteries of dogs are treated by direct injection with fibrin glue. During its injection, influx of fibrin glue was prevented by occlusion of the aneurysmal orifices with inflated polyethylene angioplastic balloons. The aneurysms which were completely (100%) filled by the injection of fibrin glue (100% infused group) were totally obliterated in 10 (71%) of the 14 cases. The parent arteries were completely preserved in all instances. Follow-up study demonstrated satisfactory maintenance of this occluded state in the aneurysms in the 100% infused group. In completely occluded cases, all aneurysms maintained this state. On the other hand, 1 of the 4 incompletely obliterated aneurysms recanalized partially. These occluded aneurysms were studied by a light microscope (LM) and a scanning electron microscope (SEM). At day 7 after the occluding procedure, the margin of the aneurysmal orifice was covered by a layer of fibroblasts. At day 21, almost half of the aneurysmal cavity had been substituted with connective tissue. The orifice of the aneurysms was covered with an endothelial layer.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1508314 TI - [Craniotomy for lesions in the cerebral convexity; how to precisely localize the lesions with conventional CT slices]. AB - A simple direct precise localization with a CT scan for convexity lesions is presented. The shape of the normal calvarium was analyzed and a characteristic pattern was obtained, that is, one spherical surface in the frontal area and 6 flat planes in the temporal, parietal and occipital areas. The temporal plane is perpendicular to the orbito-meatal line (OML), while the parietal plane declined 29 degrees in the A-P view, and the occipital plane declined 60 degrees in the lateral view. A summit of these three planes forming the parietal tubercle, and the crest following the tubercle between the parietal and occipital planes were detected either by CT scan, or by palpating the skull. Conventional methods of preoperative localization include measurement and calculation from the base line such as OML, or obtaining a CT scan with a marker on the scalp. The former might have an error that will be amplified in the parietal region that would not be negligible. The latter is a rather troublesome method demanding that the CT scan be taken after shaving the hair. Landmarks utilized for the localization should be identified both on the CT scan and on the scalp or skull. These involved OML, coronal suture, parietal tubercle, inion, pineal body, midline and so on. Of these, the coronal suture runs almost perpendicular to the OML and would be the best landmark for the localization in the parietal area.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1508315 TI - [Fresh fracture of the odontoid process treated with direct screw fixation; a case report]. AB - A case of a fresh type II fracture (Anderson & D'Alonzo) of the odontoid process treated with direct screw fixation is reported. A 52-year-old man complained of severe neck pain following a hit on his forehead incurred in a falling accident. Neurological examination was normal. Cervical spine x-ray films and axial CT scans revealed a fracture at the base of the dens. It was slightly oblique leftup and rightdown, and the dens fragment was displaced 3mm lateral to the right. One week after the injury, this odontoid fracture was directly fixed with a compression screw by an anterior cervical approach. Immediately after the operation, his neck pain disappeared. He had only 4 days of bed rest and 2 months of external immobilization with a simple neck collar. He returned to his previous job 2 months after surgery without any limitation of his neck movement. At follow up examination 16.5 months after the operation, x-ray films demonstrated complete fusion of the fracture and no problem about the screw such as displacement or breakage. Direct screw fixation of an odontoid fracture via a transcervical approach was thought to be a reasonable method of treatment. For proper assembly of this method, the following two points are particularly recommended: a screw insertion perpendicular to the fracture plane and the use of an optimal screw with both the desired total and thread lengths. PMID- 1508316 TI - [Unilateral agenesis of the internal carotid artery in a patient with ruptured aneurysm of the anterior communicating artery; a case report]. AB - This 27-year-old female suffered from subarachnoid hemorrhage. Angiography revealed a ruptured aneurysm of the anterior communicating artery. Unilateral absence of the right internal carotid artery was also demonstrated angiographically. Both the right anterior and middle cerebral arteries were perfused from the left carotid artery via the anterior communicating artery. Absence of the right carotid canal was proved on bone CT. Neuroradiological difficulties in differential diagnosis between agenesis and aplasia of the internal carotid artery were discussed. Subsequently, a diagnosis of adult type unilateral agenesis of the internal carotid artery with collateral circulation was made. The mechanism of association of cerebral aneurysm in patients with agenesis of the internal carotid artery was also discussed. From our experience, abnormal vascular anatomy should be carefully studied prior to direct surgery for a ruptured aneurysm in patients with unilateral agenesis of the internal carotid artery. PMID- 1508317 TI - [A case of an cerebello-pontine angle pineoblastoma]. AB - An extremely rare case of a left cerebello-pontine angle (CP angle) pineoblastoma has been reported. The patient was a 32-year-old male whose initial manifestations were those of increased intracranial pressure. CT scan showed a large enhancing mass located at the left CP angle, associated with a moderate occlusive hydrocephalus. Left suboccipital craniectomy was performed. The mass was an extramedullary tumor which had compressed the left cerebellar hemisphere, and was easily separable from the adjacent tissue. The tumor was totally resected, and the patient had a temporary release from the symptoms. Recurrence and spinal dissemination were found within the ensuing few months. The tumor had invaded deeply through the left CP angle into the cerebellar parenchyme, and showed no anatomical connection with the pineal body. The tumor dissemination was also observed widely in the spinal subarachnoid space. No abnormalities at the pineal region were able to be confirmed using CT and MRI studies. Irradiation to the whole brain, to the localized left CP angle and to the spinal cord with additional chemotherapy was given. The patient died half a year after the first operation. Autopsy was not performed. Histopathologically, the tumor was delineated into lobular structures by reticulin fibrils and vimentin-positive interstitial tissue. Tumor cells were small in size, and had irregularly shaped hyperchromatic nuclei with increased mitotic figures, and formed various types of rosettes; pineocytomatous, Flexner-Wintersteiner, Homer-Wright and perivascular. Fine argyrophilic cell processes with club-shaped expansions were demonstrated inside the pineocytomatous rosettes.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1508318 TI - [Bilateral distal anterior cerebral artery aneurysms associated with polycystic kidney and liver disease; a case report]. AB - A patient who had bilateral distal anterior cerebral artery aneurysms and a right middle cerebral artery aneurysm in association with polycystic kidney and liver disease is reported. A 57-year-old woman was referred to our center with headache and disturbance of consciousness. On admission, her level of consciousness as evaluated by the Japan Coma Scale was 10. CT revealed subarachnoid hemorrhage, especially in the interhemispheric fissures. Right carotid angiography demonstrated bilateral distal anterior cerebral artery aneurysms and a right middle cerebral artery aneurysm. All three aneurysms were clipped in a one-stage procedure. The patient was discharged without any neurological deficits two weeks after the operation. Bilateral distal anterior cerebral artery aneurysms are extremely rare. This is the first report of such aneurysms and a right middle cerebral artery aneurysm in association with polycystic kidney and liver disease. The etiology of these aneurysms is discussed. PMID- 1508319 TI - [Treatment of arteriovenous fistula in the skull base; a case of von Recklinghausen's disease]. AB - We presented a case of neurofibromatosis associated with intractable arteriovenous fistula of the internal carotid artery in the skull base. A 41-year old man presenting dyspnea and neck swelling was treated with balloon occlusion for arteriovenous fistula. This was followed by its total removal. At operation, we found that arteriovenous fistula was formed by the invasion of the internal carotid arterial wall of a neurofibroma in the skull base, which had been induced by neurofibromatosis. This is a rare case corresponding to vascular neurofibromatosis in the internal carotid artery. PMID- 1508321 TI - Current bibliographies of neuropeptides prepared by the University of Sheffield Biomedical Information Service. PMID- 1508320 TI - [Rapid resolution of acute subdural hematoma; report of two cases]. AB - We reported two cases of rapid resolution of acute subdural hematoma. Case 1, a 21-year-old female, sustained head trauma and became unconscious for about 15 min. Probably she was suffering from posttraumatic amnesia for about 1 day. On admission J.C.S and G.C.S were 20 and 9 (2 + 2 + 5) points, respectively. Neurological examination showed no abnormalities. An initial computed tomography (CT) scan taken 2 hours after the injury showed a high dense subdural hematoma on the left cerebral hemisphere and hemispheric swelling. She was conservatively treated. A follow up CT scan taken 8 hours after the injury disclosed rapid disappearance of the hematoma and cerebral swelling. Case 2a 23-year-old male, sustained head trauma and became unconscious for about 30 min. On admission J.C.S and G.C.S were 1 and 14 (4 + 4 + 6) points, respectively, and slight right hemiparesis was noted. An initial CT scan taken 2 hours after the injury showed subdural hematoma of the left cerebral hemisphere and hemispheric swelling. He was conservatively treated. A follow up CT scan taken 24 hours after the injury revealed almost complete disappearance of the subdural hematoma and cerebral swelling. It was suggested that the rapid resolution of acute subdural hematoma was attributable to redistribution due to decrease of ICP, and washing out by cerebrospinal fluid. PMID- 1508322 TI - Impaired PRL response to hyperthermia in alcoholic men. AB - The aim of this study was to evaluate the release of PRL to sauna-induced hyperthermia in 10 chronically alcohol-addicted male subjects after a few weeks of abstinence. In contrast with normal men the alcoholic men showed higher basal levels of PRL and the exposure to hyperthermic stress did not stimulate in PRL secretion. These results indicate that chronic alcohol abuse is associated with functional pituitary alterations similar to other states of addiction. PMID- 1508323 TI - Preprothyrotropin-releasing hormone mRNA and TRH are present in the rat heart. AB - PreproTRH mRNA has been identified in rat cardiac tissues by Northern analyses and RNase protection assays with a specific rat 32P-TRH cRNA probe. Densitometric analyses revealed that atrial ppTRH mRNA concentrations were approximately five fold greater than those of the ventricles. TRH concentrations (RIA), by contrast, were two-fold higher in ventricles. These data suggest that TRH and TRH mRNA are present in the rat heart, but their concentrations are dissociated, possibly because of differential post-transcriptional or post-translational processing. TRH is postulated to play an autocrine or paracrine role in cardiac physiology. PMID- 1508324 TI - Mobilization of calcium from intracellular store as a possible mechanism underlying the anti-opioid effect of angiotensin II. AB - Angiotensin II (AII), injected intracerebroventricularly, has been shown to antagonize opioid analgesia. The mechanism for this was obscure. In the neuroblastoma X glioma NG 108-15 hybrid cell line, the K(+)-induced increase in [Ca2+]i can be suppressed by the delta opioid agonist [D-Pen2, D-Pen5]enkephalin (DPDPE) at 0.01-1 microM, an effect completely reversed by the opioid antagonist naloxone. Angiotensin II (AII) at concentrations of 0.1 and 1 microM mobilized free Ca2+ from an intracellular pool, and this effect was antagonized by the AII receptor antagonist saralasin. All (1 microM) had no significant effect on the increase in [Ca2+]i induced by K+, but it blocked the suppressive effect of DPDPE on the K(+)-induced [Ca2+]i increase. The results indicate that mobilization of intracellular calcium may underlie the anti-opioid effect of AII. PMID- 1508325 TI - A neurosecretory granule Lys-Arg Ca(2+)-dependent endopeptidase putatively involved in prooxytocin and provasopressin processing. AB - A Ca(2+)-dependent endopeptidase cleaving at the carboxyl side of the paired Lys Arg residues has been found in the neurosecretory granules of the rat neurointermediate pituitary. The specificity pattern on synthetic fluorogenic substrates, the inhibitor profile, the pH optimum of 5.0 and the Ca(2+) dependence are compatible with an involvement of this enzyme in the prooxytocin and the provasopressin processing within the granules. The enzymatic features of the neurohypophysial granule endopeptidase resemble those of the insulinoma granule type II endopeptidase and suggest that the same Ca(2+)-dependent protease or closely related enzymes could be involved in processing Lys-Arg-containing prohormones in neuroendocrine cells. PMID- 1508326 TI - Decreased numbers of cholecystokinin-immunoreactive nerve cells in the cerebral cortex of LEC rats with a hereditary hepatitis. AB - The distribution of CCK-immunoreactive cells was investigated by the indirect fluorescence method in the cerebral cortex of LEC (Long-Evans Cinnamon) rats which have recently been introduced as a model of jaundice and hepatic encephalopathy. Reduction of CCK-immunoreactive nerve cells was observed in the brains of LEC rats with stage III to V hepatic encephalopathy in comparison with the rats without hepatic encephalopathy. These observations were confirmed by counting the CCK-positive nerve cells at magnification x 125. 3 microscopic fields per animal were immunostained and CCK-immunoreactive nerve cells counted. The number of CCK-immunoreactive cells per field was 28.5 +/- 0.7 (mean +/- SEM, n = 5) in rats without hepatic encephalopathy, and 14.1 +/- 2.0 (n = 3) in rats with stage III to V hepatic encephalopathy. Thus, the number of CCK immunoreactive nerve cells was significantly less in rats with stage III to V hepatic encephalopathy (p less than 0.05). A decrease in CCK-immunoreactive nerve cells was not observed in the rats with stage I or II hepatic encephalopathy. This study shows that there is a relationship between the severity of hepatic encephalopathy and the number of CCK-immunoreactive nerve cells in the cerebral cortex. PMID- 1508327 TI - Rapid, high-yield isolation of human chromogranin A from chromaffin granules of pheochromocytomas. AB - Chromogranin A (CgA) is a useful probe of human neuroendocrine neoplasia and exocytotic sympathoadrenal activity, but the application of CgA immunoassays has not been widespread because of limited availability of purified human CgA. Here we describe a rapid, high yield isolation of human CgA. After obtaining and lysing pheochromocytoma chromaffin granules, the soluble core proteins (chromogranins) were depleted of dopamine-beta-hydroxylase by passage over a concanavalin A-Sepharose affinity column, then lyophilized, resuspended in volatile buffer, and gel filtered on Sephacryl S-300. SDS-PAGE-analyzed column fractions contained homogeneous human CgA, which was verified structurally (N terminal amino acid sequence) and immunologically (radioimmunoassay and immunoblot). The overall 22.6 mg yield of purified CgA represented 5.7% of the starting vesicle core protein. This preparation will be useful in evaluating the sympathoadrenal system and endocrine neoplasia in man. PMID- 1508328 TI - A neuropharmacological analysis of compensatory-restorative processes in organic deficit of the parafascicular complex of the thalamus. AB - It has been demonstrated in freely behaving cats, on the basis of a model of the biological precursors of concrete and abstract thinking, that, in the presence of a neurosurgical lesion of various divisions of the parafascicular complex of the thalamus, the restoration of disturbed functions by neuropharmacological agents through an effect on dopamine-, choline-, and GABAergic systems is possible. There is specialization in the neurochemical pathways of the lateral and medial regions of the complex, which opens the possibility of the topical correction of psychopathology of the thalamic level. PMID- 1508329 TI - Intercentral relationships of cortical bioelectrical activity of the human brain following operative interventions in brainstem structures. AB - The dynamics of the total bioelectrical activity and the parameters of its intercentral interaction was investigated in 52 neurosurgical patients with a focal lesion at the level of the brainstem with the aim of analysis of the compensatory neurodynamic reorganizations of the human brain in the early postoperative period. The study was based on the precise verification of the topography of the pathological focus within the limits of the brainstem; on the dynamic clinical-neurological assessment of different variants of the postoperative course; and on a study of the structure of cortical bioelectrical activity based on visual and spectral coherence analysis. The dependance is demonstrated of the compensatory neurodynamic reorganizations of the brain on the character and degree of the stem lesion (transitory, stable, irreversible). PMID- 1508330 TI - Interactions of motivation and reinforcement during the performance of a simple instrumental reflex by a monkey. AB - The dynamics of the performance of an instrumental task by Macaca rhesus monkeys was investigated in an automated experiment. Three monkeys were trained to complete a movement with a lever in response to a light stimulus. It was demonstrated that the performance of the instrumental reflex by the monkeys is comprised of the alternation of blocks of more or less continuous realizations and pauses between them. The relationship of the intensity of the work of the monkeys to the time from the beginning of the experiment was studied, and a comparison was made of the magnitude of the intensity for the three monkeys. The average intensity of the work of the monkeys within the blocks of continuous realizations is a constant and individual value. The influence of the degree of deprivation and of the delivery of out-of-turn reinforcement on the work of the monkeys was also investigated. PMID- 1508331 TI - Xenografting of embryonal tissue of the neocortex into aged animals. PMID- 1508332 TI - Influence of pyrogens on the ultrastructure of reticular nuclei and the nucleus magnus of the raphe of the cat medulla oblongata. PMID- 1508333 TI - Biofeedback control of systemic arterial pressure. AB - The central mechanisms and possibilities of biofeedback of the systemic arterial pressure have been investigated in experiments on cats, rabbits, and rats. The adaptive processes were followed in association with minimization of electrodermal reinforcement during the development of shifts in relation to the level and bioelectrical structure of the AP, as well as the impulse activity of hypothalamic neurons. PMID- 1508334 TI - Catalepsy and hyperkinesis induced by the chronic injection of a tetrapeptide into the neostriatum. AB - The influence on behavior of the chronic (over the course of three weeks) injection of leu-enkephalin and its analog, a tetrapeptide, in doses of 5 and 15 micrograms, into the neostriatum was investigated in experiments on rats. Native enkephalin had little effect, but the tetrapeptide in both doses blocked conditioned reflex avoidance behavior and induced a set of complex changes in behavior. Catalepsy with pronounced waxy rigidity of the skeletal musculature was the main element of the pathological behavior. Stereotypical slow movements of the head and forelimbs began to predominate on the second week of the microinjections. Changes in behavior but without catalepsy and hyperkinesis were observed on the following days. It is hypothesized that the phenomena described are associated with reorganizations of neuromediator systems that accompany the chronic influence on the opiate system of the neostriatum. The role of the enkephalinergic system in the genesis of psychomotor deviations is discussed, as well as the possibility of obtaining through the method utilized of models of neurological and psychopathological deviations. PMID- 1508335 TI - Localization of neurons innervating the upper portion of the duodenum in the motor nucleus of the vagus nerve. AB - Using the method of the retrograde axonal transport of horseradish peroxidase and a microelectrode technique, a population of neurons sending axons to the upper portion of the duodenum was identified in the dorsal motor nucleus of the vagus nerve. It was established that the maximal number of such neurons was located 1.0 2.5 mm rostral to the obex. The effects of their stimulation on the electrical activity of the smooth muscles of the duodenum was studied. PMID- 1508336 TI - Perception of temperature elevation in human seasonal heat adaptation. AB - Higher values of the exponent power function of the perception of temperature elevation (1.66, 1.32, and 1.50) in the summer than in the winter (1.40, 1.08, and 0.84) were established in seasonal investigations in people at room air temperatures of 20, 28, and 40 degrees C. Consequently, following adaptation to the seasonal high temperature a person can feel a smaller temperature increment than in the winter. This suggests a reorganization in the functional activity of the temperature analyzer under the prolonged influence of seasonal high temperature. PMID- 1508337 TI - Correction of apathic-abulic manifestations of the processual defect by cholinotropic preparations. PMID- 1508338 TI - Features of the electrical reactions of the sensorimotor cortex to real and mental movement in left-handed and ambidextrous individuals with speech disorders at age six to seven years. PMID- 1508339 TI - Correlation analysis of EEG rhythms and functional asymmetry of the hemispheres in children with the hyperdynamic syndrome. PMID- 1508340 TI - [Hormonal and metabolic response to trauma: physiopathology and therapeutic management]. AB - This article is a review of present knowledge of the hormonal and metabolic responses to trauma and surgery. The factors which may mediate the responses are discussed and the potential value of different therapeutic manipulations are reviewed. The accelerated breakdown of muscle following significant injury is the most characteristic feature of the metabolic response. The magnitude of the muscle wasting that is potentially proportional to the extent of injury, leads to a marked cachexia which could be considered a part of the multiple organ failure. It does seem that the protein loss and the immunodepression which often occurs after major trauma may be important factors in determining morbidity and mortality of the patients. The prevention or the attenuation of the metabolic stress response could be beneficial in improving immunocompetence and minimizing complications after major trauma or surgery so that an earlier return to normal health could be achieved. At present there are few epidemiological data to support this view but it is an attractive concept in the management of a severely ill patients. We are aware that anaesthetic techniques, nutritional support, normothermia and hormonal manipulation can modify part of the hormonal and metabolic response to surgery. The knowledge of all of them and the clinical implications that their use could have, will be helpful to the anaesthesiologists and the Intensive Care physicians in their daily working in the operation theatre, intensive care unit or in the surgical ward. PMID- 1508341 TI - [Transesophageal echo-Doppler in children: the importance of the exact measurement of the aortic diameter and its variations over time for estimating the aortic output]. AB - The purpose of the study was to evaluate a new non invasive system of hemodynamic monitoring. The aortic systolic, diastolic and mean diameter have been measured with eco-TM and the aortic blood flow with pulsed Doppler, in order to obtain the aortic output. The aortic systolic diameter and the derived aortic output were then compared to the corresponding values obtained with CT. Ten healthy children were asked to be explored with CT under general anaesthesia and an oesophageal probe was positioned. The mean aortic diameter value was 7.18 +/- 0.91 mm. The systolic and diastolic aortic diameter was 7.87 +/- 0.91 mm and 6.65 +/- 1 mm respectively. The aortic systolic diameter measured with CT was 8.2 +/- 0.92 mm. Correlation analysis with aortic systolic diameter with eco TM as the dependent variable and aortic systolic diameter with CT as the independent variable revealed a highly significant correlation (r = 0.95, coefficient of determination 0.90). The mean percentage difference between systolic and diastolic diameter measured with TM eco scan was 15% with maximum variation 22% and minimum of 10% (p less than 0.003). The aortic blood flow calculated from the systolic aortic diameter was 29% higher than that obtained from diastolic aortic diameter. This would suggest that the correct measurement of the aortic diameter has to be considered in the final evaluation of aortic output especially in children in whom the elasticity of the aortic wall represents a major factor in determining fluctuations of aortic diameter. PMID- 1508342 TI - [Hypoxemia after heart surgery. An exception or a normal development?]. AB - The course of respiratory exchange through arterial blood gas analysis after coronary bypass-grafting and valvular replacement has been investigated in a cohort of 62 patients. Arterial blood gases were measured at baseline (the day before surgery), and then 1, 2, 3 and 9 days after surgery; in a subset of 18 patients, randomly selected from the same population, pulmonary function tests were also performed at baseline and repeated on day 9. Arterial blood gases showed a remarkable prevalence of hypoxaemia (as defined as arterial PaO2 less than 60 mmHg): 31% on the first, 50% on the second, and 40% on the third post operative day; anemia and desaturated mixed venous blood were also prominent findings during the first two days. Arterial PO2 resulted higher afterward, although its mean value then was significantly lower than baseline (81.5 +/- 8.8 vs 93.1 +/- 9 mmHg, p less than 0.005). Pulmonary function tests evidenced widespread restrictive changes, with alterated thoraco-pulmonary mechanics (loss of more than 40% of vital capacity and one second forced expiratory flow) and parenchimal lung damage (residual volume and CO diffusion capacity decrease). Some differences in PaO2 course between coronary patients and valvular patients have been releaved; the mean basal PaO2 value of valvular was significantly lower then the other one (86.7 +/- 10.8 vs 94.7 +/- 10.9, p less than 0.05). PMID- 1508343 TI - [Comparison between propofol and isoflurane in patients undergoing aorto-coronary bypass. Effect on systemic and coronary circulation]. AB - The Authors report their experience with the use of two different anaesthetic techniques (propofol-fentanil versus isoflurane-fentanyl) for induction and maintenance of anaesthesia in patients undergoing coronary artery surgery. Haemodynamic data (regarding systemic and coronary circulation) showed an almost similar pattern of change after induction, intubation, skin incision and sterotomy, except for a greater decrease of systemic vascular resistances after induction in patients who received propofol. Cardiac output decreased more in the isoflurane group while changes in coronary sinus flow were equal in the two groups. PMID- 1508344 TI - [Alfentanyl and midazolam in combined anesthesia. Clinical evaluation]. AB - We have evaluated the effectiveness of a technique of blended anaesthesia (epidural-general) in 31 patients undergoing major surgery. Thoracic epidural blockade with lidocaina CO2, adrenalin 1/200000, ensures analgesia while induction and hypnosis maintenance were obtained with midazolam, alfentanil, atracurium and N2O/O2. This technique seems able to protect the patients from endotracheal intubation and surgical stress and also to enable a rapid, quiet awakening. The dose of midazolam necessary to maintain hypnosis was inversely proportional to the patient's age. The reversal of hypnosis was necessary in 4 patients only. PMID- 1508345 TI - [Long-term sedation with propofol in ICU: hemocoagulation problems]. AB - The Authors have studied the effects of propofol on coagulation in 15 patients admitted to ICU. Propofol was used for long-term sedation (therapeutic range 3 mg/kg/h). Variables monitored included: platelets, PTT, PT, Fibrinogen, FDP, AT III. The effects on coagulation has been investigated in three groups of patients: group I) 5 patients that received propofol for 1-3 days; group II) 5 patients that received propofol for 4-10 days; group III) 5 patients that received propofol for 11-35 days. No difference were found about blood coagulation in this groups of patients before and after administration of propofol. PMID- 1508346 TI - [Effects of propofol and isoflurane on the neuromuscular block induced by atracurium]. AB - Speed of onset, duration of action and recovery time for a bolus injection of atracurium were measured in two groups of patients. In group I anaesthesia considered of propofol, fentanyl, nitrous oxide and oxygen mixture. The induction dose of propofol was 2 mg/kg-1 followed by an infusion of 9.0 mg/kg-1/h-1 for first half hour and 4.5 mg/Kg-1/h-1 subsequently. In group II anaesthesia consisted of isoflurane, fentanyl, nitrous oxide and oxygen mixture. Isoflurane was given upon clinical needs. Speed of onset, duration of action, and recovery time for atracurium were measured in the two groups. No statistically significant differences between speed of onset and duration of action between the two groups were found. The recovery period from T1 = 10% to T1 = 70% twitch response was considerably longer with isoflurane (25 min +/- 6) than with propofol (18 min +/- 3) (p less than 0.01). Results obtained suggest that for adequate relaxation during tracheal intubation smaller doses of atracurium are not needed during isoflurane than propofol administration. Because of the longer recovery period of residual neuromuscular blockade during isoflurane anaesthesia decreasing doses of atracurium and careful monitoring of twitch depression tension are also suggested. PMID- 1508348 TI - [Multiorgan damage in exertion heatstroke]. AB - The paper reports a fatal case of exertion heat stroke. The etiopathogenetic, clinical and therapeutic aspects of the case are described; although rarely observed, this pathology must be taken into account by the intensive care unit in order to ensure rapid aid and treatment in an attempt to modify the severe prognosis due to multiorgan damage which increases with the intensity and duration of hyperthermia. PMID- 1508347 TI - [Thoraco-abdominal binding in the treatment of overdistention of the lung bases in children]. AB - In the patient with homogeneously or inhomogeneously distributed atelectasis, localized primarily in the apices, overdistension of the non-dependent portion of the lung bases, only partially surrounded by the rib cage, is generally observed during mechanical ventilation. This phenomenon is even more pronounced in the neonate and in the infant because their rib cage compliance is almost infinite. In order to protect the lung bases in the event of their overdistension and/or to reexpand the atelectasis of the upper lobes we apply an external resistance, in form of thoracoabdominal binding, to limit the movement of the diaphragm. The degree of the binding's tension is regulated according to the degree of the distension of the lung bases detected on chest x-ray. This restriction was so far applied in 12 children using elastic bandages. We have used the thoraco-abdominal binding with good result in the treatment of atelectasis of the upper lobes, in extensive atelectasis as well as in the treatment of primitive lung bases overdistension, as described in 3 cases reports. We suggest this technique in order to obtain an homogeneous ventilation along the longitudinal axis of the lung. This method does not interfere with prone-supine postural changes, systematically applied in our department, and therefore, the homogeneous ventilation along the vertical axis is also provided. PMID- 1508349 TI - [The external jugular vein course as surface landmark in subclavian perivascular block]. AB - A study of 88 orthopaedic patients undergoing upper limb surgery, was carried out using the external jugular vein as surface landmark of the brachial plexus in subclavian perivascular technique. A significant statistical relationship was found between the insertion point of the needle, relatively to the external jugular vein course, and the block outcome. The best results were observed when the needle was inserted on the postero-lateral side of the vein or when the insertion point coincided with the vein course. Worse results were obtained by foreward insertion. So the external jugular vein could be used as surface landmark to improve the plexus localization in the subclavian perivascular technique of brachial plexus anaesthesia. PMID- 1508350 TI - [A new approach to the brachial plexus]. AB - In order to avoid complications such as pneumothorax or subarachnoid injection, the paper proposes a new approach to brachial plexus using a supraclavear route based on the pulse of the subclavian artery and 7th cervical vertebra. Complications are unlikely using this route. PMID- 1508351 TI - [Changes in the plasma amino acid profile in critically ill patients during total parenteral therapy]. AB - The aim of this study was to evaluate the kinetics of arterial plasma amino acid profile during the first 48 h of clinical TPN in order to assess the time necessary to reach the steady-state condition during infusion. Each patient was treated with one of three different amino acid solutions yielding, in the same nitrogen intake, different intakes of individual amino acids. We found four different kinetics for the administered amino acids: an increase of plasma levels immediately after the start of the TPN with no variations during the steady period; the same trend with the steady-state obtained after 6-24 h of TPN infusion; no influence at all; a decrease of fasting plasma levels with the steady-state attained variably during the study period. Each given amino acid showed a different trend partly depending on the supply, suggesting that the steady-state was reached sooner for most amino acids, when the supply was larger. With lower intakes, plasma levels were unaffected or decreased. We conclude that in critically ill patients at least 24 h are needed to obtain stable arterial plasma amino acid concentration during TPN with adequate intakes of amino acid. Knowledge offers the possibility for a quick and accurate assessment of the adequacy of a given preparation (tailored for critically ill patients), it reduces the time span of the study and, as a consequence, the influence of varied metabolic conditions. PMID- 1508352 TI - [General anesthesia for magnetic resonance. Experience on 100 cases]. AB - The diffusion of magnetic resonance imaging as a powerful non-invasive diagnostic procedure has led to an increasing request for general anaesthesia in patients who cannot lie still and/or who cannot guarantee adequate spontaneous breathing during the procedure. We report our own experience in 100 patients of this kind, in whom the need for general anaesthesia was due to neurological problems and/or tender age. Anaesthesia and monitoring devices were either devoted of ferromagnetic properties (allowing their location near the patient; as the ARM S88 portable ventilator, which we used for adult patients) or connected to the patient with long connectors (allowing their location outside the resonance magnetic field; as the Draeger-Babylog pressometric ventilator, which we used in pediatric patients). On these bases administration of intravenous (86 patients) and inhalation (14 patients) anaesthesia during magnetic resonance proved safe in our experience. PMID- 1508353 TI - [SCS (spinal cord stimulation) in severe ischemia of the legs]. AB - Spinal cord stimulation (SCS) of the low thoracic spinal epidural space was carried out in 11 patients with pain from peripheral arterial disease of the lower limbs. Conservative treatment or vasoactive drugs also failed. Results are reported relating to pain, exercise endurance on the bicycle ergometer, trophic lesion changes and TCpO2. After a mean postimulation follow-up period of 15 months, substantial pain relief was preoperative non healing skin ulcerations, but gangrenous conditions were not benefited. Exercise tolerance as measured on a bicycle ergometer increased by 40%. It is concluded that SCS is vary promising in severe limb ischemia where reconstruction surgery is not possible or has been unsuccessful. PMID- 1508354 TI - [Anesthesia with high dosage fentanyl in coronary patients: effects of pretreatment with droperidol and diazepam]. AB - The Authors have considered the effects of droperidol or diazepam treatments in patients undergoing high-dose fentanyl anesthesia in cardiac surgery. Twenty patients have been examined and divided in two groups: group A received droperidol (0.2 mg.kg-1) and group B diazepam (0.1 mg.kg-1) five minutes after fentanyl anesthesia induction (500 micrograms.min-1) to reach the "sleep dose". The diazepam pretreatment, as regards droperidol, reduces a dose of fentanyl necessary to obtain the conscience loss (21.5 +/- 2.5 micrograms.kg-1 vs 28 +/- 2.9 micrograms.kg-1). Hemodynamically the droperidol group is very stable, whereas the diazepam group shows certain myocardial depression and less protection at the OTI time. PMID- 1508355 TI - [Peridural anesthesia with 0.5% bupivacaine-fentanyl. Evaluation of the pre heating effect]. AB - The effect of preheated (37 degrees C) mixture of 0.5% bupivacaine and fentanyl on peridural anaesthesia have been studied in a double blind randomized clinical trial. Fifty patients of both sexes, ASA I-II, undergoing elective surgery for inguinal hernia repair or radical saphenectomy have been randomly assigned either to the control group (n = 25) receiving 0.5% bupivacaine-fentanyl at room temperature (20 degrees C), or to the group receiving the same anaesthetic mixture preheated for 12 hours up to 37 degrees C (n = 25). The latency period, extension, duration and quality of anaesthetic block were evaluated. A significative difference in the extension of anaesthetic block was detected at 6' (p less than 0.05 for extension up to T10 and T11, p less than 0.025 up to T12), and at 8' (less than 0.05 for extension up to T10). However no difference was observed between the two groups at 10' and later. The use of 0.5% bupivacaine fentanyl mixture resulted in a short latency period, as previously observed, and its preheating does not seem to affect substantially the parameters evaluated in this study. PMID- 1508356 TI - [Sub-arachnoid anesthesia with Sprotte and Whitacre types atraumatic needles in cesarean section]. AB - Fifty patients undergoing cesarean section with spinal anaesthesia received hyperbaric 1% bupivacaine at the L1-L2-, L2-L3 or L3-L4 interspace. Intrathecal injection was performed with a 24 gauge Sprotte needle in 35 patients and a 25 gauge Whitacre needle in 15. Successful anaesthesia was obtained in 49 patients (98%). Fluid loading with 1 litre of crystalloid before spinal block was used for prophylaxis of hypotension. 36 patients (72%) received ephedrine iv after spinal injection. All newborns were in good condition (Apgar score greater than or equal to 9). No post-spinal headache was reported. Our experience confirms the smaller incidence of headache with the pencil point needles compared with conventional needles, the effectiveness of the method and the pleasurableness of the procedure for the mothers. PMID- 1508357 TI - [Sodium naproxen in postoperative pain in orthopedics. Comparison of 2 different doses]. AB - In order to use etiopathogenetic criteria for the treatment of postsurgical pain, non-steroid anti-inflammatory drugs (NSAIDs) can be used rather than narcotic analgesics. These agents are often classified as peripherally acting analgesic drugs; nevertheless in the last years many pages have who showed a central supraspinal analgesic effect. Sodium naproxen is commonly used in the treatment of postoperative orthopedic pain because of its pharmacokinetic properties. The aim of this study was to evaluate the suitable dosage of sodium naproxen for post surgical pain relief. Forty patients submitted to foot surgery were randomized into two groups of 20 patients each. At the end of surgery one group of patients (group I) received sodium naproxen 275 mg i.m.; the same dose was administered after 12 hours. A second group (group II) received sodium naproxen 550 mg i.m. at the same time intervals. Based on a Descriptive scale for algometric measurements, the results showed significant differences in analgesic activity for the two treatments. The best results (70% of patients with no pain or slight pain vs 20% of patients) were obtained in the group that received sodium naproxen at the higher dosage (p less than 0.001). No differences were observed in the incidence of side-effects in the two groups. These results are discussed. PMID- 1508358 TI - [Determination of drug costs in general anesthesia]. AB - Drug costs of various general anaesthesia techniques have been assessed. These costs are used as a basis to point out the economies that could be made in the conduct of general anaesthesia. PMID- 1508359 TI - [Epidemiology of malignant hyperthermia in Piedmont and Valle d'Acosta. A study conducted with 2 different methods]. AB - The Authors report on the results of two researchers about malignant hyperthermia (MH) carried out in Piemont and Valle D'Aosta using two different methods. The former, based on a form sent to 492 anaesthesists got 22.7 per cent answers. They indicated 4 cases of MH during the years between 1982 and 1986, out of 213,444 narcoses with an average rate of 1:71,000. The latter was canned and by questioning directly the head physicians of anaesthesia and reanimation wards about the occurrence of MH in Piemont and Valle D'Aosta in the years between 1984 and 1988. According to this research, there were 5 cases out of 891,729 narcoses (that is 1:178,346). PMID- 1508360 TI - [Neuroleptic malignant syndrome. Problems of differential diagnosis. Description of a clinical case]. AB - Neuroleptic malignant syndrome (NMS) in its most severe form ranging from disorders of consciousness to coma is now reported relatively frequently in intensive care journals. Having observed such a case in the intensive care ward of their hospital, the Authors investigate the possibility of differential diagnosis between this syndrome and other prevalently psychiatric and non psychiatric types. It is underlined that the diagnosis of NMS is not straightforward taking into account both the type of patients who are mainly affected, that is to say psychopathic subjects undergoing prolonged therapy with heavy tranquillisers, in poor general condition, sometimes abandoned and then found in coma, and the fact that some psychiatric syndromes or drug overdoses may led to similar symptoms but require completely different treatment. PMID- 1508361 TI - [A case of double valve substitution in a female patient carrier of a factor X deficiency]. AB - We present the clinical case of a patient affected by mitral and aortic valvular disease submitted to double valvular replacement. This patient was also affected by congenital deficiency of factor X. We describe the normal problems encountered in cardiac surgery and the specific implications of this clinical case. PMID- 1508362 TI - [Anesthesia of the brain stem after a retrobulbar block. Description of 2 cases]. AB - The Authors report two cases of central nervous system complications after retrobulbar block. These complications have a 0.044% incidence in 4500 subsequent cases of retrobulbar blockade studied from 1981 to 1990. The Authors attribute the respiratory arrest and coma to direct access of the anesthetic to the central nervous system along the subdural space in the optic nerve sheath. PMID- 1508363 TI - [Multiorgan failure syndrome in multiple pregnancy gestosis]. AB - The Authors report a clinical case of Multi Organ Failure in a young woman who had given birth to triplets. After a short recall of Multi Organ Failure Syndrome, the Authors describe the clinical course and the therapy used in this case. PMID- 1508364 TI - [Rhabdomyolysis in meningoencephalitis caused by echovirus]. AB - We report one case of atraumatic rhabdomyolysis associated with Echo group viral encephalitis, not complicated by acute renal failure. Clinical and bio-humoral outlines are described, characterized by favourable evolution despite high muscular enzymatic peaks. We emphasize that the positive course is probably due to the early institution of prophylactic measures, and that, anyway, the subject still remains exposed to major rhabdomyolysis risk in the presence of stress factors, including general anesthesia. PMID- 1508365 TI - [Bilateral pneumonia caused by Chlamydia psittaci. Description of a clinical case]. AB - A mortal case of atypical pneumonia due to Chlamydia psittaci with acute respiratory distress, septic shock and multiple organ failure is described. Infection has been caused by an ill parrot imported clandestinely. Antibody titration with the immunofluorescence technique allowed diagnosis. PMID- 1508366 TI - [Synchronous and metachronous carcinomas of the large intestine]. AB - The authors present their experience relative to 5 patients with multiple carcinomas (synchronous and metachronous) of the large bowel. They underline that full examination of the colon before operation in all patients with primary colorectal cancer is necessary, and they propose a lifelong follow-up program after resection for early detection of multiple carcinomas. PMID- 1508367 TI - [Tumors of the small intestine. Case reports and comments]. AB - Tumours of the small intestine are extremely rare and have a particularly severe prognosis. The impossibility of making an early diagnosis due to the scarcity of precise symptoms during the early stages of the disease and the lack of safe instrumental tests limits the results of treatment which is essentially surgical. In order to contribute to the study of the disease and improve its prognosis, the authors report the cases which they have observed and review the literature. PMID- 1508369 TI - [Anaplastic carcinoma of the thyroid. Our experience]. AB - Nineteen patients, 12 females and 7 males, with mean age of 66 years, with anaplastic carcinoma of the thyroid, were treated between 1976 and 1990. At diagnosis, in 4 patients disease presented as intraglandular mass, in 11 as infiltration of the adjacent structures and as distant metastases in 4 cases. A preceding history of goiter was found in 7 patients. Total thyroidectomy was performed in 9 patients, subtotal thyroidectomy in 1 and a diagnostic biopsy only in 4 cases. All patients received external radiotherapy (4000-6000 rads). Median global survival was 6 months with no difference between patients receiving thyroidectomy plus RT or biopsy plus RT. All patients died of tumor except 1 who is alive and free of disease at 120 months. Combination modality treatment of anaplastic carcinoma of the thyroid represent, at times, a rational palliative therapeutic approach, even if, in selected patients with early intraglandular disease, total surgery may represent a curative therapy. PMID- 1508368 TI - [Gastric leiomyoma. Our cases]. AB - The authors describe 3 cases of gastric leiomyoma which they observed in the ten year period 1980-1990. The most important aspects of this pathology are illustrated, emphasizing on one hand the slight incidence, also due to their underestimation, the seat represented by the body and gastric antrum, the asymptomatic submucosal growth or with atypical symptomatology; on the other hand, the low malignant potential linked above all to the voluminous bulk of the neoplasm. PMID- 1508370 TI - [Postoperative infections. A prospective analysis of 1396 cases]. AB - Postoperative infections are the most frequent complications in surgery and are the commonest cause of the lengthening of hospital stay. The purpose of this study is to prospectively evaluate the incidence and predisposing factors of postoperative infections in 1396 surgical patients admitted to our Institute from 1984 to 1988. Patients undergoing minor surgical procedures (wound less than 2 cm) were excluded from the study. Patients were evaluated daily during hospital stay for onset of infections and results recorded on data sheet. Hemocultures in septic patients and samples of exudate at site of infection were taken whenever possible for aerobic and anaerobic cultures. 368 patients (26.36%) had at least one postoperative septic complication; (79 of them [5.65%] had two or more infections). The following infections were recorded: wound infections: 148 (10.60%); respiratory tract infections: 144 (10.31%); urinary tract infections 125 (8.95%); miscellaneous infections 11 (0.78%); thrombophlebitis 23 (1.64%); FUO 10 (0.71%). The most important predisposing factor for wound infection was endogenous contamination (wound infections: 18/499 [3.60%] in clean, 42/594 [7.67%] in potentially contaminated, 57/217 [26.26%] in contaminated and 31/86 [36.04%] in dirty operations). The duration of the anaesthesia was found to correlate with an increased incidence of respiratory tract infections (4.49% anaesthesia less than 60 min; 7.21% anaesthesia greater than 60 less than 120 min; 15.31% greater than 120 min anaesthesia). Urinary infections were more frequent when the patients where catheterized at least once in the postoperative period (24.86% vs 3.2%). PMID- 1508371 TI - [The surgical treatment of biliary lithiasis in the patient of an advanced age]. AB - The paper reports the authors' experience in the treatment of biliary lithiasis in elderly patients. The indications for surgery are examined taking into account the possibilities offered by the introduction of new technologies, and in particular preoperative EPST. PMID- 1508372 TI - [The late complications and nutritional follow-up in 96 patients who underwent a total gastrectomy]. AB - Clinical and nutritional follow-up was performed in 96 patients who had undergone total gastrectomy. We studied the incidence of clinical complications and alterations of nutritional parameters in those patients who had undergone curative resection and were alive and free of neoplastic disease 1 year (36 patients) and 2 years (26 patients) after operation. We observed a very low incidence of late complications, and nutritional parameters, 1 year and 2 years after operation, were normal in almost all the patients. We obtained these results because we performed a Roux en Y esophagojejunostomy using an at least 60 cm-loop; we also adopted a strict and rigorous follow-up, able to guarantee an adequate daily calorie intake. In fact, a close relationship between calorie intake and the variations of nutritional parameters was observed. PMID- 1508374 TI - [A case of primary carcinoma of the duodenum with subampullar localization]. AB - The authors illustrate a case of previous duodenal adenocarcinoma with subvaterian localization and, after revising the literature and some general remarks, they explain their practice. They come to the conclusion that in some well selected cases, duodenal segmental resection can be correctly applied. They remember that the most important factor of the improvement of the prognosis is early diagnosis: it is indispensable for radical exerectical therapy. PMID- 1508373 TI - [Massive metachronous inguinal metastases of carcinoma of the anal margin. A clinical case report]. AB - The authors report a case of epidermoid carcinoma of the anal margin with repeated metachronous metastases in the inguinal lymph nodes. The treatment of synchronous ad metachronous metastases is briefly discussed through a literature review. PMID- 1508375 TI - [Warthin's tumor of the parotid. The signs of a case]. AB - The authors report a case of Warthin's tumor associated with cat scratch disease placed in 2 nodes. Both arose at the same time and evolved rapidly. Diagnosis was made by histology after their removal. We underline the rarity of the pathology, the frequent diagnosis made after operation and recommend enuclouresection of neoplasm as the first choice, considering the benignity of the lesion and the modest aggression allowed. PMID- 1508376 TI - [Pentoxiphylline reduces the replication of HIV]. PMID- 1508377 TI - [Usefulness and limits of a fetal biophysical profile in the management of pregnancy at risk]. AB - Usefulness and limits of fetal biophysical profile (BPP) were determined in 132 high-risk pregnancies, evaluating the relationship between the last biophysical profile result and perinatal outcome. The presence of a low incidence of perinatal complications when BPP is normal permits the conservative management of these pregnancies. When the score is abnormal instead, there is also high false positive rate that may determine an unnecessary intervention with associated perinatal morbidity. On the other hand, BPP seems to become abnormal relatively late in the chronic asphyxial process, when it may be impossible to prevent mortality or a serious perinatal morbidity: its association with other tests is therefore necessary for a better evaluation of fetal risk. PMID- 1508378 TI - [Proposal for the treatment of cervix dysplasia with immunomodulators]. AB - The study included 60 patients: 43 suffered from slight portio dysplasia (12 had HPV infection also), while 17 had moderate dysplasia (7 had HPV infections also). The treatment was carried out by self-administration in 3 stages: attack (50 mg of thymopentin by s.c. injection every day for two weeks); maintenance (50 mg of thymopentin by s.c. injection every other day for ten weeks); recall 6 months after (50 mg of thymopentin every day for 4 weeks). The drug was well tolerated by all of the patients and the recovery rate in a 9-months follow-up period was significantly higher versus an historical control group. PMID- 1508379 TI - [Effectiveness of transdermal administration of 17-beta-estradiol in the management of menopause]. AB - Seventeen-beta-estradiol administered via a transdermic route was used to treat menopausal symptoms. The results obtained demonstrate the drug's good level of tolerability and considerable efficacy. PMID- 1508380 TI - [Conservative treatment of tubal pregnancy with parenteral administration of methotrexate. Case contribution]. AB - Three subjects with tubal ectopic pregnancy were treated with intravenous administration of methotrexate followed by oral administration of folinic acid. The treatment was effective in obtaining the resolution of ectopic pregnancies in all cases. Tubal patency was also preserved. PMID- 1508382 TI - [Calcium folate in pregnancy. Therapeutic efficacy]. AB - An open, randomised multicentre study was carried out to compare pregnant women, treated with calcium folinate (Citofolin Bracco S.p.A.) 15 mg/day per os starting from the 12th or 20th week of gestation, with an untreated group. The results obtained confirm the efficacy of calcium folinate treatment on the trends of parameters analysed (serum and endoerythrocytic folatemia, hemoglobin and sideremia) which remained within the normal range. Moreover, no adverse effects of any type were reported during the study. PMID- 1508381 TI - [Use of nabumetone in the treatment of primary dysmenorrhea. Report of 100 cases]. AB - The aim of the study was to assess the efficacy and tolerability of nabumetone, a new nonsteroid anti-inflammatory agent with analgesic and antipyretic functions, in the treatment of primary dysmenorrhea in 100 patients. Treatment was administered at a dose of 1 g per day for slight and moderate cases and 2 g per day for severe forms, starting from the onset of painful symptoms and lasting while they persisted. Side effects were observed in 7% of cases but were limited to the gastroenteric tract. The analysis of results confirms that with regard to the remission of symptoms, treatment was efficacious from the second month and that a further improvement was obtained with continued treatment. However, the Authors observed that, although the remission of symptoms was partial in the majority of cases, there was a greater response in cases of moderate or severe dysmenorrhea and their duration was shorter in comparison to those months in which patients had not received nabumetone treatment. PMID- 1508383 TI - [A case of surgical ligature of the sacro-iliac joint from Renaissance Central Italy]. AB - The paper reports a case of interbone ligature between the sacrum and right ileum using copper wire in an adult woman whose skeleton, dating from approximately 1600-1700 A.D., was exhumed from the Church of Sant'Egidio in Borrello (Chieti). Having described the ligature and the techniques used, the Authors discuss the reasons for the operation. In conclusion, it is suggested that the most plausible hypothesis is that it represent an interbone ligature during the course of autopsy to allow the recomposition of a corpse with a sacro-ileal dislocation. The absence of signs of sacro-ileal dislocation caused by mechanical levers during the course of autopsy leads the Authors to suppose the sacro-ileal rupture occurred while the subject was still alive. The Authors therefore hypothesise that the woman died while giving birth following the laceration of the pubic symphysis and rupture of the right sacro-ileal joint. The hypothesis of a corpse restoration is also suggested. PMID- 1508384 TI - [Fetal bradycardia during the second stage of labor. Study of 72 cases]. AB - The Authors analyse cardiotocographic patterns characterized by a constant frequency level below 120 beats/minute during the second stage of labour. Some aspects of "terminal bradycardia" (length, amplitude of oscillations, fetal heart rate in the 30 minutes preceding the onset of bradycardia) are related with the condition of the newborn (1st and 5th minute Apgar-score). Terminal bradycardia (Fischer 3, Melchior 2, 3 and 4, 2nd and 4th of Thiery) seems to have an unfavourable prognostic value especially when prolonged (more than 20 minutes), associated with low base-line variability and when cardiotocographic pattern previous to the fall of frequency is characterized by variable and late decelerations. PMID- 1508385 TI - [Pseudomyxoma of the peritoneum caused by rupture of a mucinous cystoma of the ovary. Description of a case]. AB - A case of pseudomyxoma peritonei originating from spontaneous rupture of an ovaric mucinous cystoma is described: in this pathology we observe the spreading throughout the peritoneal cavity of free or encapsulated gelatinous masses arising from primitive lesion. The examined case presented a spreading of mucinous masses on contralateral ovary and omentum and a total laparo hysterectomy, bilateral annessiectomy and omentectomy has been carried out. A year after surgery, on the base of a three months follow-up, no clinical or ultrasonic signs of local recurrence has been noticed. The pathogenesis of this pathology is discussed: the flogistic hypothesis considering such a spreading as a "foreign body" peritonitis and the neoplastic one, pointing out a metastatic process of mucus-secretive epithelia implantation as the etiopathogenetic moment of the injury, are actually the most accredited hypothesis by literature. PMID- 1508386 TI - [Bilateral ovariectomy in gonadal dysgenesis with a Y chromosome]. AB - The Authors report 4 cases of gonadal dysgenesis with a Y chromosome. Every patient underwent bilateral oophorectomy. Two cases of streak gonads, 1 case of streak gonad and gonadoblastoma and 1 case of non metastasizing bilateral gonadoblastoma with foci of dysgerminoma have been found. The Authors emphasize the importance of early bilateral gonadectomy in all cases of gonadal dysgenesis with a Y chromosome. PMID- 1508388 TI - [Effects of estradiol on in vitro cultures of human fibroblasts]. AB - This paper assesses the effect of estradiol on the in vitro growth of fibroblast taken from human breast skin. It was observed that estrogens stimulate the proliferation of phenotypically adult fibroblasts; that there is a threshold increase of hormonal concentration which can trigger off this process; and that the size of the single dose is more important than the number of doses of hormone received. PMID- 1508387 TI - [An unusual case of regular menstrual cycles and endocrine pattern typical for the reproductive age in a patient of advanced age]. AB - The Authors report the persistence of regular menses in a very old woman. Although in the absence of a pulsatile gonadotropin pattern the patient showed estradiol levels typical of the reproductive age. PMID- 1508389 TI - Effect of different agonistic experiences on behavioural seizures in fully amygdala kindled rats. AB - Fully amygdala kindled rats were exposed to two different inter-male agonistic experiences in order to study the interaction between epilepsy and acute social stress. Victory experience did not influence the severity of seizure behaviour, whereas a single acute defeat modified both ictal and postictal seizure manifestations. Defeat resulted in less severe and shorter lasting motor seizures, and the accompanied postictal inhibition or behavioural depression was of shorter duration in comparison with pre-stress values. The ability of acute defeat to trigger anticonvulsant activity as implied by the weakened convulsive response is discussed. PMID- 1508390 TI - Hippocampal kindling leads to different changes in paired-pulse depression of local evoked field potentials in CA1 area and in fascia dentata. AB - Monosynaptic evoked field potentials (EPs) in response to paired-pulse stimulation (20 ms interval) were recorded in area CA1 and fascia dentata of the same animal in the course of development of a kindled focus in the CA1 region. A significant reduction of paired pulse depression in response to medium and high stimulation intensity was found in CA1. A similar change was found in the fascia dentata in response to medium intensity stimulation of the angular bundle. In contrast, at high intensity, paired pulse depression was enhanced in the fascia dentata in the course of kindling. These results indicate that kindling epileptogenesis is accompanied by regionally different changes in recurrent inhibition: a reduction in CA1 and intensity dependent changes in fascia dentata. PMID- 1508391 TI - Different functional pools of acetylcholinesterase induce changes in rat locus coeruleus noradrenaline metabolism. AB - The effects of acetylcholinesterase (AChE) inhibition in the locus coeruleus (LC) were studied in rats utilizing fasciculin (FAS) and BW248c51 (BW). Both inhibitors were stereotaxically injected into the right LC and the animals were sacrificed 24 h later. Similar groups received atropine (30 mg/kg i.p.) every 5 h during 24 h. Another group of FAS-treated rats received naloxone twice (5 mg/kg i.p.) in 24 h. Other groups of FAS-treated rats were sacrificed 3 and 7 days after injection. An inhibition of 70% of LC AChE activity was observed 24 h after FAS or BW injection. Either FAS or BW induced a significant increase in NA levels in the injected LC compared to control values. Atropine treatment failed to block the FAS effect but it was able to counteract the BW-induced NA increase. NA levels were still increased 3 days after FAS treatment and returned to control values at day 7. PMID- 1508392 TI - Evidence for genetic determination in human twins of olfactory thresholds for a standard odorant. AB - Olfactory thresholds for four odorants were determined in groups of monozygotic and dizygotic human twins. Odorants were presented in an ascending dilution series in odorless solvent, using a three-way forced choice method. For two of the tested odorants, 5 alpha-androst-16-en-3-one and isoamyl acetate, the thresholds showed a strong genetic component. This was demonstrated by respective values of 0.78 and 0.73 for the intraclass correlation difference, and of z = 3.69 and z = 2.71 in a within-pair difference analysis. The results for isoamyl acetate are novel, and suggest that genetic polymorphism in the affinity of odorant receptor proteins contributes to the (nearly normal) threshold distribution for this odorant. PMID- 1508393 TI - Photo-ablation of single neurons in the fly visual system reveals neural circuit for the detection of small moving objects. AB - Many animals use relative motion to segregate objects from their background. Nerve cells tuned to this visual cue have been found in various animal groups, such as insects, amphibians, birds and mammals. Well examined examples are the figure detection (FD) cells in the visual system of the blowfly. The mechanism that tunes a particular FD-cell, the FD1-cell, to small-field motion is analyzed by injecting individual visual interneurons with a fluorescent dye and ablating them by illumination with a laser beam. In this way, it is shown that the FD1 cell acquires its specific spatial tuning by inhibitory input from an identified GABAergic cell, the ventral centrifugal horizontal (VCH)-cell which is most sensitive to coherent large-field motion in front of both eyes. For the first time, the detection of small objects by evaluation of their motion parallax, thus, can be attributed to synaptic interactions between identified neurons. PMID- 1508394 TI - Effects of locus ceruleus lesions on the pericapillary nerve terminals in the feline brain. AB - The effects of bilateral locus ceruleus (LC) lesions on the pericapillary nerve terminals were investigated in the feline brain parenchyma using electron microscopy. LC lesions were induced stereotaxically and the animals were sacrificed after intravenous administration of 5-hydroxydopamine (5-OHDA). The diameter and number of dense-cored vesicles (DCVs) and clear vesicles (CVs) in the pericapillary nerve terminals were measured. The number of DCVs in the nerve terminal was significantly decreased by bilateral LC lesions. The diameters of the DCVs and CVs decreased significantly as compared with those in the non operated control group. These data suggest that the LC is closely related to the pericapillary nerve terminals in the brain parenchyma and that not only nerve terminals with DCVs but also those with CVs are affected by LC lesions. PMID- 1508395 TI - Preservation of Gi-protein inhibited adenylyl cyclase activity in the brains of patients with Alzheimer's disease. AB - The coupling of inhibitory guanine nucleotide binding (Gi) proteins to the adenylyl cyclase signal transduction complex was compared in 4 brain regions from a series of Alzheimer's disease and matched control subjects by measuring the inhibition of membrane enzyme activities in response to guanosine 5'-[beta gamma imido]diphosphate (Gpp[NH]p) and aluminium fluoride (AlF4-). Basal adenylyl cyclase activities were significantly lower in preparations of angular gyrus and frontal and temporal cortices, but not cerebellum, from the Alzheimer's disease cases compared to controls. Gpp[NH]p and AlF4- gave significant inhibitions of adenylyl cyclase activity in all brain regions. The magnitude of these inhibitions, when corrected for altered basal activities, were similar for the Alzheimer's disease and control cases. These results indicate that there is no impairment of Gi-protein mediated inhibition of adenylyl cyclase activity in Alzheimer's disease brain. PMID- 1508396 TI - Concurrent wet dog shaking and inhibition of male rat copulation after ventromedial brainstem injection of the 5-HT2 agonist DOI. AB - Systemic administration of drugs that augment 5-HT2 activity generally induces 'wet dog' shaking (WDS) in rats. This suggests that the naturally occurring form of WDS seen in untreated rats may also serve as a behavioral index of 5-HT2 receptor activation, during the performance of other behaviors. Indeed, spontaneously occurring WDS has previously been reported to be inversely related to male rat copulatory proficiency. In order to examine a potential central nervous system mechanism subsuming these behaviors, male rats were tested for WDS and sexual behavior after brainstem administration of the 5-HT2 agonist DOI. Male Long-Evans rats were implanted with cannulae terminating in the region of the nucleus raphe obscurus/inferior olive, through which they received injections of DOI (0.1-10 micrograms). DOI produced a dose-dependent decrease in sexual behavior and concurrent increase in WDS. Pretreatment with the 5-HT2 antagonist ritanserin effectively blocked the effects of DOI. The results suggest that WDS and copulatory behaviors are modulated by a shared brainstem substrate. It is possible that the results may be the behavioral concomitant of recently described brainstem cells, with bifurcating axons, that project to both the medial preoptic area and the cervical spinal cord. PMID- 1508397 TI - Serotonin is found in myelinated axons of the dorsolateral funiculus in monkeys. AB - Physiological measurements suggest that the inhibition of primate spinothalamic tract cells by serotonin is mediated by myelinated axons. Previous morphologic studies emphasize that most serotonin-containing axons in the spinal cord are unmyelinated. Accordingly, the possibility that some serotonin-containing axons in the primate dorsolateral funiculus of the spinal cord are myelinated was investigated. Macaque monkeys were given L-tryptophan and the monoamine oxidase inhibitor, nialamide, intraperitoneally 1 h prior to sacrifice to increase axonal stores of serotonin. The animals were perfused (0.05 or 0.5% glutaraldehyde, 4% paraformaldehyde), and transverse sections of the thoracic cord were reacted with antibody against serotonin and then prepared for electron microscopy. Many of the immunostained axons in the dorsolateral funiculus included fine, myelinated fibers with diameters of 0.7-2.2 microns. Unmyelinated serotonin-containing axons were also observed. The observation of myelinated serotonin-containing axons in the white matter of the monkey dorsolateral funiculus contradicts the view that the descending serotoninergic projection consists entirely of unmyelinated fibers, particularly since the conduction velocity of the fine fibers would be too slow to account for the earliest latency of descending inhibition following stimulation in the brainstem. The presence of myelinated serotoninergic axons presumably accounts for the latencies reported for the inhibition of primate spinothalamic cells following stimulation of the periaqueductal gray, an inhibition that can be blocked with serotonin antagonists and that is associated with the release of serotonin in the dorsal horn. PMID- 1508398 TI - Passive electrophysiological properties of aged and axotomized cat spinal cord motoneurons: the effect of cell size and electrode shunt. AB - Intracellular recordings were obtained from intact and axotomized lumbar motoneurons of aged cats. The sub-threshold electrical properties of these cells were measured, including input resistance, resting membrane potential, and the first two equalizing time constants as well as their associated amplitude constants. These data were used in a semi-infinite cable model of the motoneuron to estimate the size of the shunt resistance (Rshunt) which is created when the electrode penetrates the cell membrane. The average Rshunt for intact aged cells was 5.35 +/- 1.01 M omega, while that for the axotomized aged cells was 8.93 +/- 1.20 M omega. The statistically significant difference in mean shunt magnitude did not affect the measurements of membrane time constant because this constant is independent of the shunt in this model of the motoneuron. However, the determination of cell input resistance, which is not independent of the shunt, was shown to underestimate the real cell input resistance by 23-29%. We therefore conclude that the shunt resistance is an important factor which should be taken into account when measuring input resistance. PMID- 1508399 TI - Near-infrared FT-Raman spectra of the rat brain tissues. AB - Near-infrared Fourier transform (FT) Raman spectroscopy was applied to brain tissues in situ. The spectra were obtained from the cerebral cortex, white matter of the cerebrum, caudate-putamen, thalamus, synaptosomal fraction, and myelin fraction. High-quality Raman spectra in the 400 to 2940 cm-1 range were measured without interference of autofluorescence. Common spectral bands were assigned. The ratios of the intensity at 1664 (amide I), 1442 (CH2 deformation), 2885 (CH2 asymmetric stretching), 2938 cm-1 (CH3 symmetric stretching) could be used for differentiation between the gray and white matters. PMID- 1508400 TI - A selective reduction of excitatory amino acids in cerebrospinal fluid of patients with Alzheimer type dementia compared with vascular dementia of the Binswanger type. AB - We determined the concentrations of the putative transmitter amino acids in the cerebrospinal fluid of patients with Alzheimer type dementia (ATD) and vascular dementia of the Binswanger type (VDBT). In ATD, aspartate and glutamate concentrations were significantly and selectively reduced, while in VDBT, concentrations of aspartate, glutamate, gamma-aminobutyric acid (GABA) and many other amino acids were decreased non-selectively. In both ATD and VDBT, we found a tendency for all amino acids to increase with progression of the disease, and this reached statistical significance for some amino acids. PMID- 1508402 TI - Delta-6 desaturation of alpha-linolenic acid in brain and liver during development and aging in the mouse. AB - During pre- and postnatal brain development, delta-6 desaturase decreased dramatically (approx. 4-fold) up to weaning, slowly (2-fold) up to 3 months, and remained nearly constant and extremely low thereafter. In contrast, in liver, the activity increased approximately 7-fold between day 3 before birth and day 11 after birth, then decreased slightly up to weaning, and was constant up to 9 months. Subsequently, the activity decreased during aging (4-fold between 9 and 26 months). During aging, the reduced activity in liver and the very low activity in brain raise the question of the origin of polyunsaturated fatty acids participating in the physiological turnover of brain membranes. PMID- 1508401 TI - Calcium dependent release of gamma-aminobutyric acid (GABA) from human cerebral cortex. AB - The release of the amino acids GABA, taurine, glycine, glutamine and leucine from human neocortex was investigated in vitro by utilizing brain tissue removed during 8 standard temporal lobectomies for epilepsy or tumor. Slices (0.5 mm thick) were cut from each biopsy and randomly placed in three different chambers. After 90 min preincubation, the three sets of slices were incubated for 60 s in wells containing, respectively, (A) regular ACSF (control), (B) ACSF with 50 mM K+ (to depolarize the cell membrane) and (C) ACSF with 50 mM K+, 0 mM Ca2+ and 4 mM Mg2+ (depolarization during blocked synaptic transmission). The content of amino acids in the wells was determined by high-performance liquid chromatography after pre-column derivatization of the amino acids with o-phthalaldehyde. Membrane depolarization (well B) increased the GABA release to 650% (620 pmol/mg) of control (well A, 95 pmol/mg). Blocking synaptic transmission (well C) reduced the evoked release by 50% (360 pmol/mg). The release of glycine, taurine, glutamine and leucine during membrane depolarization was not significantly different from the control values. The data provide evidence for a Ca(2+) dependent release of GABA, supporting a possible role of this amino acid as a neurotransmitter in human neocortex. PMID- 1508403 TI - Improved direct sequencing of Alzheimer's amyloid precursor protein (APP) exons 16 and 17. AB - Direct sequencing of exon 17 of the amyloid precursor protein (APP) gene led to the identification of 3 different types of APP717 pathogenic mutations associated with familial Alzheimer's disease (FAD). The low frequency of these mutations results in having to screen many samples in order to identify new families affected by them, which is laborious and time consuming. Thus, in order to help the identification of these mutations in additional countries and to search for new mutations in APP, perhaps in other exons also causing FAD, we have optimized the procedure and reduced the time necessary for sample preparation from 11 h to 3 1/2 h. PMID- 1508404 TI - 5-Hydroxytryptophan (5-HTP) augments spontaneous and evoked phrenic motoneuron discharge in spinalized rats. AB - Experiments on anesthetized, spinalized rats were conducted to determine the effects of systemic 5-hydroxytryptophan (5-HTP) administration on: (1) spontaneous phrenic nerve activity and (2) evoked phrenic responses to short latency, non-serotonergic synaptic inputs elicited by electrical stimulation of lateral funiculus. 5-HTP augmented spontaneous phrenic activity and allowed expression of a second, longer latency evoked response. Both effects were antagonized by methysergide. Our results suggest that spinal serotonin increases the efficacy of synaptic inputs to phrenic motoneurons. PMID- 1508405 TI - Endogenous opioid regulation of norepinephrine release in guinea pig hippocampus. AB - Release of endogenous norepinephrine was detected in guinea pig hippocampal slices using a radioligand displacement assay. Focal electrical stimulation released endogenous norepinephrine and caused a calcium-dependent reduction in specific [3H]propranolol binding at beta-adrenergic receptors in the brain slice. The mu-opioid agonist PL017 decreased norepinephrine release, and the inhibition by PL017 could be blocked by the opioid antagonist naloxone. Endogenous opioid peptides concomitantly released by tissue stimulation also decreased norepinephrine release in a naloxone-sensitive manner. These results support the hypothesis that endogenous opioids can regulate excitability in the hippocampus by presynaptic modulation of norepinephrine release. PMID- 1508406 TI - Concentrations of serotonin and its related substances in the cerebrospinal fluid in patients with Alzheimer type dementia. AB - We studied concentrations of free and total serotonin (5-hydroxytryptamine, 5-HT) and its related substances in the cerebrospinal fluid from patients with Alzheimer type dementia (ATD) compared with controls. In ATD patients, concentrations of total 5-HT, tryptophan, 5-hydroxytryptophan (5-HTP), melatonin, kynurenine, and 3-hydroxykynurenine decreased significantly. The rate of concentration of tryptophan metabolites to that of tryptophan was significantly reduced for total 5-HT and 3-hydroxykynurenine only. The 5-hydroxyindoleacetic acid (5-HIAA)/5-HT ratio was significantly larger in ATD patients than in controls. The greater reduction in the 3-hydroxykynurenine concentration (81% vs. controls) than in the total 5-HT concentration (51% vs. controls) suggests that the metabolism of tryptophan to 5-HT and 3-hydroxykynurenine is in favor of 5-HT. PMID- 1508407 TI - Theta rhythms in the rat medial entorhinal cortex in vitro: evidence for involvement of muscarinic receptors. AB - Slice preparation obtained from the rat were used to study cholinergically induced field potentials in the medial entorhinal cortex. Perfusion of slices containing medial entorhinal cortex with acetylcholine, muscarine and eserine induced theta-like activity in a frequency range of 3-10 Hz and an amplitude of 200-300 microV. Nicotine, in contrast, did not produce any rhythmical slow waveforms. The cholinergically induced theta-like oscillations were abolished by perfusion of the muscarinic antagonists atropine sulphate and scopolamine but were unaffected by the nicotine blockers hexamethonium and mecamylamine. PMID- 1508408 TI - Comparison of screening approaches. AB - Neurobehavioral techniques have been used extensively in animal toxicology studies because, in many cases, such procedures are designed to evaluate neurobiological functions thought to be affected in chemical-exposed humans, e.g., changes in sensorimotor function. Procedures used to identify or screen for the presence of neurotoxicity are usually designed to test large numbers of animals and are not considered to be as sensitive to subtle effects as more specialized tests for neurobiological dysfunction. For purposes of screening, the use of a functional observational battery (FOB) is now generally accepted. In general, FOB evaluations in animals are similar to clinical neurological examinations in humans in that they rate the presence and, in some cases, the severity of behavioral and neurological signs. A number of batteries containing different observations and measurements have been developed in several laboratories for rodents, dogs, and non-human primates. Frequently, the FOB is used in conjunction with other measures of neurotoxicity, i.e., neuropathology or sensory evoked potentials. FOB used in screening typically assess several neurobiological domains including neuromuscular (i.e., weakness, incoordination, abnormal movements, gait, motor seizures, myoclonia, rigidity and tremor), sensory (i.e., auditory, visual and somatosensory) and autonomic (i.e., pupil response, salivation) functions. Most FOB used for screening do not assess cognitive function (i.e., learning and memory). FOB evaluations can yield important information concerning dose-response characteristics and data on the onset, duration and persistence of an effect. FOB should be able to differentiate neurotoxicants from non-neurotoxicants and neurotoxicants having different mechanism(s) or site(s) of action. PMID- 1508409 TI - Proceedings of the 3rd meeting of the International Neurotoxicology Association. Parma, Italy, July 1-5, 1991. PMID- 1508410 TI - Neuroplasticity, the aging brain, and Alzheimer's disease. AB - A variety of neurological disorders are associated with the loss of specific populations of neurons. Alzheimer's, Parkinson's, and Huntington's diseases present unique constellations of behavioral and neurological abnormalities which result from the degeneration of neurons in specific regions of the brain. Approaches to the treatment of these neurodegenerative disorders have met with either limited or no success. New treatment strategies based upon a better understanding of the inherent mechanisms of neuroplasticity might provide more rational approaches to prevent, limit, or treat these and other neurodegenerative disorders. The development and standardization of appropriate animal models of neurodegenerative disorders will be essential to realize this possibility. Using the cholinergic neurotoxin AF64A we have developed a rodent model of cholinergic hypofunction that exhibits behavioral, anatomical, and neurochemical deficits very analogous to those observed in Alzheimer's disease. Furthermore, we have found that administration of neurotrophic factors, such as ganglioside AGF2, and the transplantation of fetal cholinergic neurons into the hippocampus can attenuate both the behavioral and neurobiological alterations induced by AF64A. These efforts should lead to the development of innovative clinical strategies and they should also help to elucidate the neurobiology of brain injury and recovery of function. PMID- 1508411 TI - Enhanced expression of glial fibrillary acidic protein and the cupric silver degeneration reaction can be used as sensitive and early indicators of neurotoxicity. AB - The mammalian central nervous system is composed of a large and diverse array of its two principle cell types, neurons and glia. Given this extreme cellular heterogeneity, it is not surprising that targets of neurotoxic insult often are diverse and unpredictable. In devising strategies to assess neurotoxicity, one must overcome the obstacle posed by not knowing where to look for damage. Our approach to the detection and localization of sites of toxicant-induced damage has been to take advantage of two general responses to nervous system insult, astrogliosis and argyrophilia. Assays for GFAP, the principle intermediate filament protein of astrocytes, have been devised to quantify astrogliosis and a modified cupric silver degeneration stain has been employed to examine patterns of argyrophilia. Using these methods, we found that increases in GFAP and the occurrence of argyrophilia are consistent responses to neurotoxic insults. Moreover, increments in these two indicators reveal dose-, time- and region dependent patterns of neurotoxicity at toxicant dosages below those that cause light microscopic evidence of cell loss or damage. The rapid onset of astrogliosis and argyrophilia following specific toxicant exposures suggests that the signals underlying these events are among the earliest that can be linked to the neurotoxic state. PMID- 1508412 TI - Perturbation of axonal elemental composition and water content: implication for neurotoxic mechanisms. AB - The concentration and distribution of labile elements in nerve cells is tightly regulated by multiple membrane transport processes and by binding to lipids and proteins. The multifaceted nature of elemental regulation provides numerous sites at which toxicants or disease processes might act to disrupt this regulation. Such disruption can affect cytoskeletal integrity, macromolecular synthesis, energy production, osmoregulation and other cellular processes. The possible role of perturbed elemental homeostasis in the mechanism of nerve injury caused by certain chemicals (e.g., acrylamide, 2,5-hexanedione) and neuropathic diseases (e.g., diabetes) has not been determined. To investigate this possibility, we have used electron probe x-ray micro-analysis (EPMA) to measure the distribution of elements and water in cellular compartments of myelinated axons (axoplasm, mitochondria) and glial cells (cytoplasm, myelin) in normal rat central and peripheral nervous systems. Results indicate that each compartment exhibits a characteristic composition of elements and water which might reflect function of that anatomical region or organelle. Injury-induced changes in elemental content of PNS axons and Schwann cells have been identified using several neurotoxic models (i.e., acrylamide, axotomy, diabetic neuropathy). Each type of injury initiated early alterations in element and water composition of both axons and glial cells. Compositional changes were specific and developed sequentially instead of simultaneously. Results of these studies suggest that, rather than being an epiphenomenon, altered elemental regulation might represent a primary component of many neurotoxic mechanisms. PMID- 1508413 TI - Ca(2+)-dependent processes as mediators of neurotoxicity. AB - The Ca2+ ion exerts a profound influence on cellular processes and an understanding of control mechanisms of intracellular Ca2 homeostasis while complex is mandatory in this discussion. The identification and recognition of prolonged sustained increase in [Ca2+]i as a manifestation of neurotoxin-induced destabilization of [Ca2+]i homeostasis will be related to a variety of neurotoxicant-induced cell injuries. The sites of toxicant interaction with ATP regulated Ca2+ pumps located in the neuronal/glial membrane and/or calciosomes; availability of Ca2+ proteins; disruption in mitochondrial mechanisms for Ca2+ storage; triggers of voltage-dependent Ca2+ channels and modulation of the Na+/Ca2+ exchanger will be identified and related to presumptive toxin action. Failure of one or more of these systems will result in continuous elevation of ionized [Ca2+]i--a reflection of Ca2+ destabilization. The targets resulting from Ca2+ destabilization will be identified, to include phospholipase C activation, PLA2 activation, protein kinase C (PKC) translocation, and activation of Ca(2+) dependent calpain 1. The use of specific inhibitors of neurotoxicity, e.g., natural sphingolipids, sphingosine, down regulation of PKC, inhibitors and activators of adenylate cyclase, and antiprotease agents will allow for investigation of the role of these final common pathways in the evolution of neurotoxicity. PMID- 1508414 TI - Cross species extrapolation in neurotoxicology: neurophysiological and neurobehavioral aspects. AB - The theory of phylogenetic continuity of animal species is the basis of any comparative or extrapolative endeavour (Calabrese, 1983). Cross species extrapolation is also a prerequisite for hazard identification in general and developmental neurotoxicology. Two steps must be distinguished: The first step is endpoint-based or qualitative, whereas the second is dose-based or quantitative. Comparison of different species, typically rodents, nonhuman primates and humans, in terms of endpoints is preferentially done within a framework of broad functional categories, such as sensory, motivational, cognitive, motor, and social variables. Within each category specific neurobehavioral as well as electrophysiological measures need to be considered; typically the degree of comparability is higher for electrophysiological than for most behavioral measures. For some frequently used behavioral endpoints in human neurotoxicology, such as psychometric IQ, there is no direct animal counterpart. Once the neural substrate of a particular neurotoxic effect has been identified, as is true for several chemicals such as the pyrethroid insecticides, the organophosphates, most nerve gases or MPTP, or if interspecies comparability in terms of endpoints has proven satisfactory, an effort towards quantitative, dose-based extrapolation is needed. Here species-specific differences in toxicokinetics and metabolism must be taken into consideration in order to arrive at valid translations of dose response contingencies. If at all possible internal rather than external doses should serve as the frame of reference here. Neurotoxic chemicals of environmental concern for which an adequate data base is available for comparative purposes include alcohol, carbon monoxide, lead, methylmercury and polychlorinated biphenyls (PCB). Principles of cross species extrapolation in neurotoxicology will be illustrated by means of representative neurobehavioral and electrophysiological findings. PMID- 1508415 TI - 2,5-Hexanedione is a potent gliatoxin in in-vitro cell cultures of the nervous system. AB - Of the metabolites of hexane, 2,5-hexanedione (2,5 HD) has the strongest neurotoxic effect. There is a wealth of experimental studies in animals showing an axonotoxic mechanism consisting of an accumulation of 10 nm neurofilaments. Only few studies deal with a possible action of 2,5-HD on Schwann cells, glia cells or both. Pure neurons, pure glia and mixed cultures prepared from dorsal root ganglia (DRG) of chick embryos were studied in this model. DRG were chosen because they constitute a linkage between the peripheral and central nervous system and provide the additional advantage of containing only few defined glial and neuronal cell types. Additionally, pure neuronal cultures of sympathetic ganglia and mixed cultures of spinal cord and brain were prepared. In cultures of the different parts of the nervous system investigated, we observed at a concentration of 0.25% 2,5-HD massive toxic alterations of glial cells, whereas neurons and neurites were virtually unaffected. PMID- 1508416 TI - Specific neurotoxic effects of different organic solvents on dissociated cultures of the nervous system. AB - Pure neurons were prepared from dorsal root ganglia (DRG) of 8 day old chick embryos (E8). The substances tested in this model were pure n-hexane, 2.5 hexanedione (2.5 HD) and methyl-ethyl-ketone (MEK). Differentiated cultures were exposed to these neurotoxins after two days in culture and then examined over a period of up to one week. For all three substances a specific neurotoxic effect could be demonstrated: (i) n-Hexane mainly altered the neurites, leading to focal swellings and in a second step to degenerative changes in glial cells; (ii) 2.5 HD had a minor effect on neurons and proved to be mainly gliatoxic; (iii) MEK primarily affected the neurons by swelling and disintegration of the cell body. PMID- 1508417 TI - Irradiation neurotoxicity assessed in organotypic cultures of rat hippocampus. AB - The neurotoxic effects of irradiation on the developing nervous system were studied in organotypic cultures of hippocampus prepared from newborn Sprague Dawley rats. Hippocampus slices of 7-day-old rats were irradiated at the day of explantation at doses of 1, 2 and 4 Gy, and cultured in a roller drum for a fortnight. Light and electron microscopy showed remarkable damage to neuronal cells following irradiation, oligodendrocytes and myelogenesis being also affected. In contrast to alterations in neuronal perikarya, no morphological changes in synapses were obvious, though their number seemed to be reduced after irradiation with 4 Gy. These results confirm that low dose radiation produces damage to the central nervous system not only pre-natally, but even in post-natal periods of differentiation and development. PMID- 1508418 TI - In vitro screening batteries for neurotoxicants. AB - The need to develop, validate and utilize in vitro models to test chemicals for neurotoxic potential is widely appreciated. This lecture discusses the major advantages of using cell and tissue culture, the various in vitro models amenable for neurotoxicity studies, and the distinction between mechanistic and screening models. Considerations for designing screening batteries to evaluate neurotoxicants are discussed. Topics such as choice of appropriate cell models and endpoints (i.e., cytotoxic and neurotoxic), and technical considerations in the design of the battery are also presented. PMID- 1508419 TI - The effects of 2,5-hexanedione on rods and cones of the retina of albino rats. AB - Light microscopic morphometry has shown that albino rats exposed to 2,5 hexanedione (2,5-HD) or 2,5-hexanediol (2,5-HDol) develop degeneration of rods and cones in a 12 hr light/12 hr darkness environment. To determine whether there is selective damage to rods or cones, 7-week old, male Sprague-Dawley rats were exposed to 2,5-HD (1%) in their drinking water during equal periods of light and darkness for 5 weeks. At the end of this time the rats were paralyzed in the hind limbs. Half were then sacrificed and studied while the remaining rats were allowed to recover for 13 weeks. A control group of rats were studied in parallel under identical conditions. The outer nuclear layer in the exposed and control rats was assessed immediately following treatment. The rods were found to be strongly selectively reduced (p less than 0.01) but the cones (2% of all photoreceptor cells) were not significantly affected. Rats permitted to recover for 13 weeks and then sacrificed had lost almost all their rods (p less than 0.001) while the cones were reduced by about 50% (p less than 0.01). Most of the rats had a moderate residue of rods and cones at the ora serrata, an area protected from light energy. These findings suggest that rods are more sensitive than cones to the toxic effects of 2,5-HD in combination with light energy. PMID- 1508420 TI - Evoked potentials are modified by long term exposure to trichloroethylene. AB - Two groups of New Zealand albino rabbits were respectively exposed to 350 and 700 ppm of trichloroethylene (TRI) 4 hrs/day, 4 days/week for 12 weeks. Weekly, visual evoked potentials (VEP) recordings were obtained under mesopic condition. Blood samples were also collected weekly to determine the concentration of TRI and its metabolites. Recordings from the 350 ppm group showed a significant (p less than 0.001) decrease in the amplitude of VEPs, while a significant (p less than 0.001) increase was observed in the 700 ppm group. Both effects were reversed to baseline values within six weeks after the last exposure. The observed modifications in VEP amplitudes were related to blood level of trichloroethanol. These results thus confirm the neuro-ophthalmotoxicity of TRI and support the hypothesis that trichloroethanol is a reliable marker of the effective neurotoxic dose of this organic solvent. PMID- 1508421 TI - Auditory brainstem evoked potentials (BAEPs) in lead-exposed workers. AB - Brainstem Evoked Potentials (BAEPs) were recorded in 49 lead exposed workers, and in a control group of 49 age- and sex-matched subjects, never exposed to neurotoxic substances. The mean duration of lead exposure was 7.4 (SD 5.6) yr. Blood lead concentration was analyzed in the morning of the experimental day (PbBc); an averaged PbB level was based on the levels of the 3 previous years (PbBm). Interpeak latency differences (IPLD) I-V, I-III and III-V were considered. The mean PbBc level was 54.6 (SD 16.1) micrograms/dl while the mean PbBm level was 53.5 (SD 15.9) micrograms/dl. Lead exposed workers showed a significant prolongation of IPLDs. IPLD I-V was longer in the subgroup with PbBm greater than 50 micrograms/dl (4.06 vs 3.98, c.l. 95% 0.00-0.16). These results are consistent with literature data and show that BAEPs may be a sensitive detector of subclinical lead effects on brainstem auditory pathways. PMID- 1508422 TI - Olfactory threshold shift following controlled 7-hour exposure to toluene and/or xylene. AB - The present study was undertaken to examine olfactory perception threshold (OPT) shift following exposure of healthy subjects to toluene and/or xylene in an inhalation chamber. Five volunteers were exposed to 50 ppm toluene, 40 ppm xylene or an additive mixture of the two, for a period of 7 consecutive hr in an inhalation chamber. A Latin square design was used and subjects were exposed over 3 consecutive days/week, with an 11-day interval between each 3-day session. Olfactory perception thresholds, measured in decismels (ds), were ascertained for both toluene and PM-carbinol, contained in 100 ml bottles with serially increasing concentrations (Olfacto-Lab Kits # 191 & 11). Test administration was based on the forced choice method. Analysis of variance of pre-exposure OPTs indicated that for both toluene and PM-carbinol, significant differences were observed between individuals (p less than 0.05), but not between days or weeks. Measurements, made immediately following exposures revealed a significant six fold increase in OPT for toluene (median: 15 ds), while PM-carbinol OPT remained stable. Individual differences were observed, but there was no effect of type of exposure, day, week, or interactions. OPT for toluene, determined at intervals following cessation of exposure, indicated a return to pre-exposure values at a mean rate of 6.8 ds/hr. The findings of this study suggest that there is a substantial olfactory threshold shift during a 7-hr period, specific to a particular solvent or family of solvents. Receptor-specific saturation is proposed as the underlying mechanism. PMID- 1508423 TI - Comparative studies on the neuro- and reproductive toxicity of acrylamide and its epoxide metabolite glycidamide in the rat. AB - The neurotoxicity of acrylamide (AA) has been the subject of extensive studies at the morphological and functional levels in both animals and man. The concern for human exposure to monomeric AA derives partly from its extensive use in molecular biology laboratories where, in the United States alone, 100,000-200,000 persons are potentially exposed. Initial work in this laboratory aiming at the development of techniques for using hemoglobin adducts as biomarkers for human exposure to AA, revealed the formation of glycidamide as a reactive epoxide metabolite of acrylamide in the rat (Chem. Res. Toxicol. 3, 406, 1990). In rats treated with 0-100 mg/kg of AA significant dose-rate effects were observed on adduct formation by both AA and glycidamide. The high rate of formation of the metabolite, especially at low doses where approximately 60% of AA was converted to glycidamide in vivo, prompted us to investigate its potential role in the induction of neurotoxic and reproductive effects attributed to AA exposure. In initial neurotoxicological experiments, the effects of the parent compound (8-14 days, 25 and 50 mg/kg/day) and the metabolite (8-14 days, 50 and 100 mg/kg/day) were compared. While at the higher dose both compounds affected the rats' performance on the rotarod, only acrylamide had a significant effect in the hindlimb splay test, which is considered a more sensitive indicator of peripheral neuropathy. On the other hand, a stronger effect was seen for glycidamide than for AA on the male reproductive system, especially on sperm cell viability.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1508424 TI - Interactive effects of toluene and hexane on behavior and neurophysiologic responses in Fischer-344 rats. AB - Solvent mixtures are ubiquitous in industrialized environments and are used frequently for recreational purposes. Toluene and hexane are common components of many solvent mixtures and have characteristic, but different, neurotoxic consequences. Interestingly, Takeuchi et al., (1981) reported that toluene attenuated the peripheral neuropathy caused by n-hexane, possibly by blocking its metabolism to 2,5-hexanedione (Perbellini, et al., 1982). To confirm such effects at higher concentrations and to examine effects on the central nervous system (CNS), four groups of 12 rats each were exposed to air, toluene (1200 ppm), hexane (4000 ppm), or a mixture of toluene (1200 ppm) and hexane (4,000 ppm) 14 hr/day for 9 weeks. A battery of behavioral and electrophysiologic tests was used to assess the functional consequences of their exposures. The battery consisted of measures of grip strength, locomotor gait and landing splay, sensory sensitivities during conditioned avoidance performance, the action potential of the ventral caudal nerve, and the brainstem auditory evoked response. Measures of peripheral nervous system functions (e.g., grip strength and conduction velocity) showed interactive effects like those reported by Takeuchi et al. Toluene greatly reduced the neuropathy caused by hexane. Hexane-induced abnormalities in central components of the brainstem response were much less reduced in the presence of toluene. There was no reciprocal action of hexane on the motor syndrome and hearing loss caused by toluene. PMID- 1508425 TI - Neurobehavioral and neuroendocrine effects of occupational exposure to perchloroethylene. AB - The hypothesis that long-term low-level exposure to perchloroethylene (PERC) may impair the dopaminergic control of prolactin (PRL) secretion and negatively affect neurobehavioral performance, was tested in a cross-sectional survey of dry cleaners. Sixty female workers exposed to PERC in dry-cleaning shops and thirty controls recruited in a cleaning plant not using solvents were examined. PERC air concentration during four-hour random periods varied from 1 to 67 ppm (median 15 ppm). PERC blood levels ranged 12-864 mg/l (median 145 mg/l). A set of tests from a computer-based performance evaluation system was administered, including Finger Tapping with both dominant and non-dominant hands, Simple Reaction Times, Digit Symbol, and Shape Comparison in two different versions constructed to test Vigilance and the response to moderate stress, respectively. During the proliferative phase of the menstrual cycle, PERC-exposed workers showed increased serum PRL (12.1 +/- 6.7 ng/ml) as compared to their matched controls (7.4 +/- 3.1 ng/ml, p less than 0.001). Prolonged reaction times were also observed in all tests. However, neither the duration of exposure nor air and blood PERC concentrations were significantly correlated with performance. Nor were exposure variables associated with the increased PRL levels. PMID- 1508426 TI - Joint effect of gestational age and maternal lead exposure on psychomotor development of the child at six years. AB - A prospective study has been carried out to assess the psychomotor deficit resulting from a moderate decrease in gestational age and pre-natal lead exposure. The general cognitive index of the McCarthy psychometric scale (adjusted for confounders) in six-year-old children was related to gestational age. Most of the psychomotor scores showed smoothing variations with gestational age ranging from 37 to 39 weeks, whereas sharp changes occurred between 39 to 40 weeks, with plateau values above such a cut-off for all spheres of development examined. Maternal hair lead content, used as an indicator of lead exposure during pregnancy, was found to be negatively related to general cognitive, verbal, quantitative, and memory subscales (p less than 0.01), whereas its relationship with perceptual and motor subscales was close to 0.05 significance level. Control for gestational age did not change the significance level of the associations. When controlling for maternal hair lead levels, the significance of the association between gestational age and the McCarthy subscales also remained stable, only the general cognitive index and verbal subscale reaching the conventional significance level. PMID- 1508427 TI - Calcium-entry blockers-induced parkinsonism: possible role of inherited susceptibility. AB - The risk of developing drug-induced parkinsonism (DIP) has been related to a number of factors but it remains up to now poorly defined. The aim of this survey has been to evaluate retrospectively the possible role of inherited components in 25 patients with parkinsonism induced by chronic exposure to the calcium-entry blockers cinnarizine and flunarizine. The finding of higher occurrence of a positive family history for Parkinson's disease (PD) and/or essential tremor (ET) and of higher frequency of secondary cases with PD and/or ET among close relatives of the patients as compared to age-matched controls, suggests the involvement of genetic susceptibility in developing this drug-induced disorder. DIP could be regarded as a multifactorial disease process resulting from potential neurotoxicity of drugs on a background of inherited predisposition. PMID- 1508428 TI - Correlations between subjective disturbances due to acute exposure to organic solvents and internal dose. AB - A general tendency to minor subjective disturbances ("susceptibility") were measured by questionnaire scores of psycho-/neurovegetative lability in 32 subjects independent of any experience with solvents. In series of experiments interrelations between subjective and biological variables during experimental exposures for 4 or 8 hr to acetone (1000 ppm), ethyl acetate (400 ppm), acetone/ethyl acetate mixture (500/200 ppm), or filtered air were investigated. Every two hr ratings of "tension", "tiredness", "complaints" and "annoyance" were reported and samples of urine were collected in order to analyse the internal dose of the substances. In exposures to ethyl acetate and to the mixture, the mean levels of urinary excretions of the substances show significant cross correlations to rated complaints and annoyance, but not to rated tension and tiredness. Those subjects who showed higher susceptibility reported higher ratings of complaints and annoyance in those exposure conditions containing ethyl acetate. In exposures to acetone these relations were not found. Both, the quality of the substances and the individual tendency to report slight health impairments influence the variability of subjective reactions on exposure to solvents. PMID- 1508429 TI - Neurotoxicology of PCBs and related compounds. AB - Polychlorinated biphenyls (PCBs) are a family of 209 chemicals with two linked phenyl rings and variable chlorination. They are clear oils at room temperature. They were produced from the 1930s until banned in the 1970s because of toxicity and evidence of widespread environmental contamination. They were used mostly as insulators in electrical equipment; their widespread occurrence in the environment is more a consequence of uncontrolled disposal than of deliberate dissemination. In Asia, there have been two outbreaks of poisoning due to cooking oil contaminated by thermally degraded PCBs. Studies in workers exposed chronically to "clean" PCBs, workers exposed acutely to thermally degraded PCBs in clean-up of fires, and adult patients in Asia who ingested contaminated rice oil consistently show slowed nerve conduction and sometimes show headache, lassitude, and other CNS symptoms. In children exposed to background levels in the US, those with the highest transplacental exposure show hypotonia and hyporeflexia at birth and slowed motor development through age two, a defect in visual memory processing at 7 mon, and defects in short term memory at 4 years. Despite the presence of PCBs in breast milk, no association between breast milk exposure and any measured outcome has been seen other than lower activity levels at 4 years among long term breast fed children at the highest PCB levels. In Asia, children who were in utero at or after the 1968 exposure in Japan or the 1979 exposure in Taiwan showed clinically evident developmental delay. In Taiwan, the children were shown to have a variety of ectodermal defects, but the association between these defects and developmental delay was weak.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1508430 TI - Preclinical neurophysiological signs of parkinsonism in occupational manganese exposure. AB - To study the effects from low level exposure to manganese, 30 men at steel smelting works and 60 nonexposed reference subjects, were neurophysiologically examined using: (i) Electroencephalogram (EEG), Event related auditory evoked potential (AEP/P300), Brain stem auditory evoked potential (BAEP) and diadochokinesometry. No group differences concerning EEG or BAEP were found. Diadochokinesis was slower and there was a tendency towards prolonged P300 latency in the exposed group as compared to the referents. These effects may be interpreted as early (subclinical) signs of disturbances of the same type as parkinsonism. PMID- 1508431 TI - Accumulation of inorganic mercury in lower motoneurons of mice. AB - The distribution of mercury within the lower brain stem and spinal cord of mice was investigated at various intervals after a single intramuscular injection of mercuric chloride. The autometallographic technique was used to demonstrate the presence of mercury deposits in tissue sections. Accumulation of mercury was observed in motoneurons of the anterior horns and in motor nuclei of the brainstem. In addition, mercury was present in the neuropil of the area postrema and within renal tubular cells. At the ultrastructural level, mercury was localized to neuronal lysosomes. The preferential accumulation of mercury in motoneurons within the spinal cord and brain stem is most probably due to an uptake of mercury in motor nerve terminals followed by retrograde axonal transport to the cell bodies. PMID- 1508432 TI - Effects of diisopropyl fluorophosphate on muscarinic-M1-receptors and on receptor mediated responsiveness of the phosphatidyl-inositol system in the cerebral cortex of rats. AB - The effects of acute and repeated treatments with an anticholinesterase (anti ChE) compound, diisopropylfluorophosphate (DFP) on M1-acetylcholine receptor (M1 AChRs) density and on M1-mediated breakdown of inositol phospholipids were studied in the cerebral cortex of rats. The DFP doses induced an about 75% inhibition of cortical ChE 48 hr after the last treatment. The acute treatment did not change Bmax of M1-AChRs (measured as 3H-pirenzepine binding), while 1 week and 2-weeks treatments induced their significant down-regulation, by 14 and 29%, respectively. The responsiveness of M1-AChRs was measured in cortical prisms as accumulation of inositol phosphate (IP) following stimulation with a cholinergic agonist, carbachol (from 10 to 1000 microM). The IP accumulation (expressed as ratio stimulated/basal IP content) was lower in acute DFP rats than in controls at few carbachol concentrations, and after 2 weeks at most carbachol concentrations. This resulted in a significant increase of EC50. The data indicate the involvement of cortical phosphatidyl inositol system during intoxication by anti-ChE agents, namely a decreased efficiency of post-receptor mechanisms. PMID- 1508433 TI - Effects of malaoxon on phosphatidylinositol signaling in convulsing and non convulsing non-pregnant and pregnant female rats and their offspring. AB - Phosphatidylinositol (PI) signaling during organophosphate (OP) induced convulsions and tissue Ca2+ changes in 10 weeks old male, and 14 weeks old non pregnant and pregnant female rats, and the offspring of the latter were explored. Brain inositol and inositol-1-phosphate (Ins1P) served as indices of alterations in brain PI signaling, and brain tissue Ca2+ as an index of early neuronal injury. A dose of malaoxon OP, which produced convulsions in about 60% of the exposed rats in different rat groups, was 39.2 for male, and 8.2 mg/kg for pregnant female rats, respectively. Malaoxon (8.2 mg/kg) did not produce convulsions in non-pregnant female rats. All the rats were followed for 1 or 4 hr subsequent to malaoxon. Malaoxon decreased cerebral inositol in both male and female rats, and the decrease was similar in spite of the dose difference. The decrease was larger in the convulsing than in the non-convulsing rats. A tendency towards a decrease of brain inositol also occurred in the offspring. Ins1P levels were markedly increased in male, and also in non-pregnant female rats, but not in the brains of pregnant female rats. Ins1P was not markedly changed in the brains of the offspring. Malaoxon elevated brain tissue Ca2+ in male but not in female rats or their offspring. Cholinergic systems and PI signaling in the brain seem to be associated with OP-induced convulsions both in male and female rats; females seem to be more sensitive than males. Malaoxon may also have slightly modified PI signaling in the offspring brain. Hormonal factors are likely to modify OP CNS toxicity and cholinergic stimulation of brain PI signaling. PMID- 1508435 TI - Regulatory developmental neurotoxicity and human risk assessment. AB - A number of efforts, in the last 15 years, have been directed at developing protocols to assess the potential developmental neurotoxicity (DN) of test agents. Japan and the United Kingdom have general protocols that describe the behavioral parameters that should be evaluated as part of other types of testing protocols, such as standard developmental and/or reproductive toxicity studies. In 1986, EPA published a proposed separate guideline for the testing of glycol ethers. Since then, this protocol has undergone extensive review and comment by an agency-wide workgroup, participants of a workshop sponsored by EPA and NIDA, EPA's Scientific Advisory Panel, and the public. Comments were taken into consideration and the final DN testing protocol has been published recently by EPA's Office of Pesticide Programs. This protocol provides specific guidance on issues of study design, aspects of CNS function to be evaluated and criteria for selection of testing procedures. It is designed to be a "generic" protocol could be applied to testing of pesticides and other chemicals and that could be modified on a case-by-case basis depending on the data available on a specific agent of concern. With the development of testing protocols for assessing DN, there comes a need for the development of guidance as to how the data should be interpreted and applied toward conducting a risk assessment for extrapolation to humans. Some guidance was developed at the EPA-NIDA Workshop. EPA has published specific risk assessment guidelines in the area of developmental toxicity that include a section on interpretation of data on functional deficits, including DN.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1508434 TI - Models for the in vitro assessment of neurotoxicity in the nervous system in relation to xenobiotic and neurotrophic factor-mediated events. AB - We have been investigating the use of three culture types for both screening and mechanistic neurotoxicology in vitro. These are the neuroblastoma cell lines (IMR32 - human; C-1300 - mouse), primary mixed monolayer cultures of the rat and chick embryonic midbrain ('micromass' systems) and organotypic whole rat brain reaggregate cultures. The performance of these models for neurotoxicity resting has been investigated with ethylcholine mustard aziridinium (ECMA), vincristine, aluminium, glutamate receptor antagonists, MPTP, and 'hypothyroidism'. From a 'screening' viewpoint, in vitro exposure through a tiered testing system (ranging from simple cytotoxicological parameters in the neural cell lines to neurotransmitter measurements in the organotypic cultures) may permit detection of CNS neurotoxicity and delineation of possible mechanisms. The type of developmental neurotoxicological information gained is highlighted in the cases of aluminum and the glutamate receptor antagonists. High concentrations of aluminum caused significant neural cell death in differentiated neuroblastoma cell lines after approximately two weeks exposure in vitro. In contrast, cell death was detected in the developing midbrain cultures as early as 24 - 48 hr. Studies in whole brain reaggregates suggest that cholinotoxicity may occur in a similar time-frame and is consistent with some of aluminium's effects in vivo. Preliminary experiments have shown that exposure of immature developing midbrain rat primary cultured neurones to the glutamate receptor antagonists, AP3 and MK 801 induces neural cell death which may relate to control of NGF by glutamate cells. Developing neural culture systems may prove useful for testing agents which cause neurotoxicity through disturbances of neurotrophic function. PMID- 1508436 TI - Reactive oxygen species: relation to aging and neurotoxic damage. AB - The inherent biochemical, anatomical and physiological characteristics of the brain make it especially vulnerable to oxidative insult. Some of the features which account for a susceptibility to free radical induced insult, include a high lipid content, a major requirement for oxidative energy metabolism, and a paucity of enzymes dissipating reactive oxygen species. Recently it has become increasingly apparent that many drug and chemical-induced toxicities may be evoked by way of oxidative stress. Major points addressed in this presentation relate to xenobiotic-induced disruption of cerebral redox status, specific examples of neurotoxic agent-induced alterations in free radical production, as measured by the fluorescent probe dichlorofluorescein, and the regulation of neural free-radical generation by antioxidants and protective enzymes. Recent attempts to unify the diffuse discipline of neurotoxicology, have led to the concept of "final common pathways" that characterize frequently occurring cellular responses to disruption of homeostasis resulting from exposure to xenobiotic agents. The present work considers the thesis that oxygen radicals may be mediators of such a "final common pathway". Free radical mechanisms may thus contribute significantly to the expression of the harmful properties of diverse, unrelated neurotoxic agents. Studies with aged animals suggest that, while excess levels of oxidative species are not apparent in the aged central nervous system, prolonged exposure to such species may adversely modify proteins, and this may be a contributing factor to senescence. The extent to which normal physiologic aging and neurotoxic events interact, remains to be determined. PMID- 1508437 TI - Craniomandibular disorders. Problems of VDU operators. PMID- 1508438 TI - Clinical dentistry. The wearing of gloves. PMID- 1508439 TI - AIDS. Reaction to HIV positive dental personnel. PMID- 1508440 TI - Fluoridation. PMID- 1508441 TI - Supplementation of domestic sugar (sucrose) with fluoride. Effects on experimental dental caries, plaque pH, and fluoride levels in plaque and enamel. AB - The minimum amount of fluoride which, when added to sucrose, will reduce caries in an intra-oral test was determined. Removable lower-arch appliances were worn by three adult subjects for 1 week, during which time plaque-covered enamel on one side was immersed in a 10 percent sucrose solution containing fluoride for 10 minutes four times per day. The effect of sucrose alone (control) was similarly determined on the other side of the appliance. Concentrations of 2 and 5 ppm F in sucrose solutions (20 and 50 ppm F dry weight) produced highly significant reductions in experimental caries of 43 and 44 percent respectively. A reduction in enamel dissolution due to re-precipitation of fluoride-rich apatite is probably largely responsible for the anti-caries effect. However, decreased plaque acid production may also play a role since the addition of 1 ppm F to 5 percent sugar reduced the plaque pH drop in artificial mouth experiments. Our results substantiate previous reports that fluoridation of sucrose to a level of 20 to 50 ppm F dry weight has potential benefits in caries prevention and may be useful when the F intake is otherwise low. PMID- 1508442 TI - Current issues in gerodontology. AB - Gerodontology involves much more than the treatment of dental disease in people aged over 65 years. Using the definition of Ettinger, a relatively distinct group of individuals are defined. However, a slightly broader definition is perhaps more appropriate, to include those who are in any way handicapped in the receipt of dental treatment due to their age. This group of patients may become victims of ageist behaviour by dentists. This may influence their treatment options, and become a barrier to older patients receiving the full range of treatment they may require. However, the elderly generally consider oral health to be of low priority, and many, including those with identifiable problems, do not have a perceived need for care. The main barrier to their seeking treatment is their own attitude to their problems, and only a few experience barriers that otherwise prevent their utilisation of dental treatment. The dental needs of the elderly can be anticipated to rise as more retain their teeth, many of which will be heavily restored. The cost of this treatment must be met by someone; if the patient cannot afford it, the State may be asked to provide the funds. On present form, the response to this suggestion is likely to be unfavourable, but a cheap alternative to specialist care is not desirable, as it will only be able to partially perform the task. There is a need for research in a variety of aspects of gerodontology.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1508443 TI - Oxygen saturation during intravenous sedation using midazolam. AB - Intravenous sedation with midazolam was given to young, fit, adult patients undergoing third molar surgery; oxygen saturation (SpO2) was continuously measured during the surgery and for 30 minutes after the surgery. There were some instances of a brief fall in the oxygen saturation, during the surgery and in the immediate period following surgery. It is suggested that it may be necessary to observe and selectively monitor some patients in the immediate post-surgical period as well as during the period of operation. Although not addressed by this investigation, this would be particularly true of medically compromised patients and the elderly. PMID- 1508444 TI - Policy document on sedation for dental procedures. PMID- 1508445 TI - Prevention of infective endocarditis associated with dental treatment and other medical interventions. PMID- 1508446 TI - Has the process causing noninsulin dependent diabetes start at birth? Evidence in neonates from a population with a high prevalence of diabetes. AB - AIMS: to investigate whether differences in the glucose-insulin axis are present at birth in neonates from ethnic groups at high risk of diabetes. METHODS: fructosamine samples were taken from Maori, European and Pacific Island expectant mothers at their 28 week appointment at the public outpatients clinic at National Women's Hospital, Auckland. Umbilical cord samples for insulin, C-peptide and fructosamine assay were taken at delivery and babies had their subscapular skinfold fat thickness measured by callipers. RESULTS: the mean maternal 28 week fructosamine was similar in the three populations in spite of a higher prevalence of gestational diabetes among Pacific Islanders. Of the 1066 deliveries, cord samples were available for 207 Europeans, 81 Maoris and 113 Pacific Islanders. Both Pacific Island and Maori babies had higher cord fructosamine concentrations than European babies. However, Pacific Island babies were also heavier, and had higher cord insulin concentrations and subscapular skinfold thickness than European babies. CONCLUSIONS: the elevated cord fructosamine concentrations suggest that Maori and Pacific Island babies, who share a high risk of noninsulin dependent diabetes mellitus later in life, are hyperglycaemic at birth. The paradoxical insulin results and the cause for the relative neonatal hyperglycemia warrant further investigation. PMID- 1508447 TI - The detection and importance of functionally abnormal haemoglobins. PMID- 1508448 TI - Death certification in Auckland. AB - AIMS: to investigate the reasons behind general practitioner referral of cases of natural death to the coroner, and also the understanding of general practitioners of the relevant legislation. METHODS: as cases of natural death were referred to the coroner over a seven month period, the deceased's general practitioner was contacted by telephone and questioned regarding his/her knowledge of the death and willingness to sign a cause of death certificate. Based upon this interview, cases were divided according to whether their general practitioner could have signed the death certificate or not. RESULTS: there were 314 cases where there was a contactable general practitioner. In 257 instances, the general practitioner would not have signed the death certificate: 183 found the death unexpected, and 74 had not seen the patient recently enough. In 57 instances the general practitioner would have signed the death certificate, but did not because: 23 were unaware of the death, 13 could not be contacted, 14 did sign a death certificate but this was rejected by the medical referee, and seven would have signed but did not for miscellaneous reasons. CONCLUSION: a disturbing finding was the general lack of understanding of certification legislation in particular the concept that the patient must have been seen in their last illness to be able to sign the death certificate. When signing death certificates, doctors should be thinking in terms of last illness rather than a vague period of time between two weeks and three months. PMID- 1508449 TI - Chorionic villus sampling in Auckland 1989-90. AB - AIMS: to perform an audit of all 197 chorionic villus sampling procedures performed in Auckland in 1989-90. METHOD: an attempt to trace the outcome in all 197 cases and this was possible in 188 cases. RESULTS: 89% of chorionic villus samples were performed transvaginally and 11% transabdominally. The total fetal loss rate was 9.6% (18) with six spontaneous miscarriages before 20 weeks gestation (3.2%), one intermediate fetal death and one neonatal death. There were 10 elective terminations of pregnancy following abnormal results so the spontaneous loss rate was 4.3%. CONCLUSIONS: the loss rate was lower than that reported in the European and Canadian multicentre trials. The sampling success rate, however, was poor with 13.7% failed procedures. This improved in the second year of the service to 10%. There were no failure cultures or examples of mosaicism. PMID- 1508450 TI - Forensic psychiatry and prison liaison services in Auckland: the first twelve months. AB - AIMS: to assess referrals to a prison liaison service of regional forensic services in Auckland. METHODS: data on forensic psychiatric referrals from Auckland prisons 1 October 1989 to 30 September 1990 were collected. This was the first year of the service. RESULTS: there were 127 forensic psychiatric referrals in the period. The characteristic profile of such a case was that of a 28.5 year old male, unemployed remanded of Maori ethnic background. The commonest charge was nonsexual assault together with a prominent history of polysubstance misuse. Schizophrenia was the most frequent diagnosis. CONCLUSIONS: these findings have implications for regional forensic psychiatry services and other mental health providers, and the community in general. PMID- 1508451 TI - Hepatitis B vaccination in children: five year booster study. AB - AIM: to demonstrate that appropriate doses of hepatitis B vaccines would be protective for at least five years in children. This would be shown by administering booster doses and measuring the response. METHODS: 2 micrograms intramuscular (IM) doses of Merck Sharp and Dohme (MSD) recombinant DNA vaccine (rDNAV) were given to 318 children who had received age appropriate doses of MSD plasma derived vaccine (PDV) five years earlier. Sera were tested for hepatitis B virus (HBV) seromarkers pre- and postbooster. RESULTS: all children who had responsed to primary immunisation demonstrated an anamnestic response. The geometric mean titre (GMT) of antibody to hepatitis B surface antigen (antiHBs) rose from 89 to 4777 IU/L. AntiHBs was detected in 94% of vaccinees just prior to the five year booster, and 96.5% a mean of 10 days later. CONCLUSION: when initial vaccine seroconversion is satisfactory, protection of responders persists for at least five years, assuming that the response to vaccine boosters mimics the response to wild virus. Therefore, for population control of hepatitis B in children in endemic areas, booster doses are not required for at least five years. PMID- 1508452 TI - Antral vascular ectasia: the watermelon stomach. AB - Antral vascular ectasia (watermelon stomach) is an uncommon localised vascular abnormality which may cause occult gastrointestinal blood loss and iron deficiency anaemia. The endoscopic appearances are characteristic with well demarcated, often raised or nodular bright red streaks radiating from the pylorus back along the antrum. Endoscopic biopsies can be taken without risk of haemorrhage and may help distinguish this condition from gastritis. The aetiology remains obscure, but there is an association with achlorhydria, hypergastrinaemia, and cirrhosis of the liver. Four patients are described; two had antrectomy with long term control of their anaemia, and two were treated conservatively. The lesion may be diagnosed more frequently with more widespread recognition of the condition. PMID- 1508453 TI - Children hospitalised with pertussis in the Bay of Plenty. PMID- 1508454 TI - Management of unstable angina by the general practitioner. I. New insights in pathophysiology and management. PMID- 1508455 TI - Health reform. PMID- 1508456 TI - Hospital waiting lists. PMID- 1508457 TI - Management nuspeak. PMID- 1508458 TI - Copper 7 IUCD. PMID- 1508459 TI - Early anaesthetics in New Zealand. PMID- 1508460 TI - Melanoma registrations. PMID- 1508461 TI - Nurses' pay--from the 1920s to today. PMID- 1508462 TI - Five common questions about the contract talks. PMID- 1508463 TI - Should nurses prescribe? PMID- 1508464 TI - How good is a polytech graduate? PMID- 1508465 TI - Handpiece disinfection. The scientific view. PMID- 1508466 TI - Learning by example. PMID- 1508467 TI - R.B. Raskin cited for distinguished service to dentistry. PMID- 1508468 TI - Peripheral trigeminal nerve injuries. AB - Certain dental procedures being performed routinely can result in nerve damage. The following is a review of some of these surgical procedures coupled with a discussion of ways to avoid, diagnose and manage the nerve injuries associated with them. PMID- 1508469 TI - Rhabdomyosarcoma of the infratemporal fossa. AB - The outlook for children suffering from this most common soft tissue sarcoma is vastly better today than it was 15 years ago, when fewer than 20 percent of its victims survived. Continuing advances in treatment should increase survival rates even more in the future. PMID- 1508470 TI - Sjogren's syndrome. Dental role in providing relief. AB - This oftentimes underappreciated disease carries with it severe dental implications, all of which can affect the patient's quality of life. While there is no cure, it is possible to manage disease symptoms and to prevent irreversible dental damage. PMID- 1508471 TI - New York State set to impose infection-control mandate. PMID- 1508473 TI - House hearing focuses on jaw implant dangers. PMID- 1508472 TI - Health department rejects mandatory HIV disclosure, but backs continuing education requirement. PMID- 1508474 TI - Distinguished Alumni Award goes to Edward G. Kaufman. PMID- 1508475 TI - Ethics: "now and forever". PMID- 1508476 TI - The MSDS crusade. PMID- 1508477 TI - Nursing documentation guidelines. PMID- 1508479 TI - The Presidential election: what if no one wins? PMID- 1508478 TI - Caring for the emerging majority. PMID- 1508480 TI - Simplified aponeurotic ptosis surgery. AB - I present a simplified aponeurotic ptosis repair that minimizes surgical dissection and enhances the predictability of postoperative eyelid positions. Indications for the procedure are unilateral ptosis, bilateral ptosis where preaponeurotic fat excision is not indicated, mild congenital ptosis, and reoperations from standard levator surgery. The procedure is best suited for surgeons who have a thorough knowledge of the levator aponeurosis anatomy. PMID- 1508481 TI - Orbital decompression for Graves' disease: exposure through a modified blepharoplasty incision. AB - A "transorbital" three-wall decompression through a modified blepharoplasty incision was used to treat 19 orbits for either cosmetic disfigurement or optic neuropathy. In the 14 orbits with disfigurement, surgical retroplacement averaged 5.2 mm; vision improved to 20/40 or better in four of five eyes with optic neuropathy. Complications attributed to the surgery included: acquired strabismus (two transient, one permanent) and infraorbital hypesthesia (one transient, one permanent). This technique's advantages are: 1) a single incision with wide exposure, 2) a low incidence of permanent strabismus, 3) a lateral orbital rim and canthal tendon preservation, and 4) a large reduction in proptosis. PMID- 1508482 TI - Effects of flurbiprofen and suprofen on the miotic activity of 1% acetylcholine and 0.01% carbachol. AB - The nonsteroidal antiinflammatory agents (NSAIAs) flurbiprofen and suprofen applied topically to reduce miosis may counteract the desired effects of miotics used during ocular surgery. In a pigmented rabbit model, 1% acetylcholine was shown to cause a greater, significant initial (for the first 30 minutes) constriction (P less than .05) than 0.01% carbachol in eyes pretreated with flurbiprofen and suprofen. From 2 to 8 hours, NSAIA pretreatment had a greater miotic effect with carbachol than with acetylcholine. There were no significant differences between flurbiprofen and suprofen on the miotic effect of carbachol or acetylcholine. PMID- 1508483 TI - Corneal edema following argon laser iridotomy. AB - Laser iridotomy is generally a safe and effective procedure for narrow-angle glaucoma. However, since surgical success with the argon laser depends on a focal thermal effect, a corneal burn is a possible complication. I describe five patients with occludable anterior chamber angles and bilateral corneal guttata who developed uniocular progressive corneal edema with visual loss following argon laser iridotomy. These five patients underwent iridotomy with a total laser energy of 63, 48.5, 7, 25, and 25 J, respectively, and began to lose vision due to corneal edema immediately, and 5, 2, 4, and 2 years later, respectively. Following penetrating keratoplasty with cataract surgery, histopathology of the corneal buttons showed generalized endothelial cell loss in all five. Microstructural findings of guttata and thickened Descemet's membrane implied that prior endothelial dystrophy had predisposed these patients to laser-induced damage. Risk factors for immediate or delayed-onset bullous keratopathy after argon laser iridotomy include prior angle closure, preexisting endothelial guttata, and high laser energy with multiple applications. Recognizing the potential of this complication offers opportunities for preventive strategies. PMID- 1508484 TI - Nonabsorbable suture material in cataract surgery: a comparison of Novafil and nylon. AB - We compared the performance of 10-0 Novafil (polybutester, Davis & Geck, American Cyanamid Company, New South Wales, Australia.) with that of 10-0 nylon (Alcon) in 60 patients undergoing extracapsular cataract extraction and implantation of a posterior chamber intraocular lens. A standard technique was used, and the incision was closed with interrupted sutures of either 10-0 Novafil or 10-0 nylon. Length of follow up ranged from 6 to 26 months (average, 15 months). We assessed the intraoperative handling qualities of the suture materials, as well as their effect on wound healing and inflammation. We also compared the surgically-induced astigmatism in the two suture groups over the first 3 postoperative months and then in long-term follow up (average, 15 months). Sutures removed at long-term follow up were examined by scanning electron microscopy (SEM). Both suture materials handled easily at operation and were well tolerated by all patients. There was no significantly different surgically induced astigmatism in the two suture groups after 12 weeks (P = .962) or during longer follow up (P = .401). SEM confirmed more advanced biodegradation of nylon as compared with Novafil sutures after they had been in place an average of 18 months. PMID- 1508485 TI - Intraocular lens implantation in an almost completely retained capsular bag with a 4.5- to 5.0-millimeter linear dumbbell opening in the human eye. AB - As a preliminary step in developing a capsular opening that will permit the firm fixation of the full-size intraocular lenses (IOLs) of the future in a completely retained capsular bag, conventional 11-millimeter long posterior chamber IOLs with 6-millimeter polymethylmethacrylate optics were implanted in almost completely retained capsular bags with a 4.5- to 5.0-millimeter linear dumbbell opening. Undergoing the procedure were 23 cataractous eyes of 23 patients (average age, 72 +/- 8 years). Average follow up was 15 +/- 2 months. The dumbbell opening was made with an automated electric trephine or manually. The Cavitron 10,000 was used for phacoemulsification. Lens epithelial cell removal was performed by cryopexy. All IOLs were fixed in the capsule satisfactorily. Although complete transparency was not retained in any of the eyes, postoperative visual acuity was better than 10/20 in 16 eyes (70%). There were no apparent complications other than anterior capsular opacification. PMID- 1508486 TI - Ciliary sulcus fixation of a dislocated posterior chamber intraocular lens using liquid perfluorophenanthrene. AB - A posterior chamber intraocular lens was transsclerally sutured to the ciliary sulcus with the aid of liquid perfluorophenanthrene (Vitreon). This vitreous substitute facilitates the procedure and reduces the possibility of damage to the retina. PMID- 1508487 TI - Management of retinal detachment associated with choroidal coloboma using perfluoroperhydrophenanthrene (Vitreon). AB - Vitreous surgery using an internal tamponading agent and chorioretinal adhesion is commonly used to repair retinal detachment associated with choroidal coloboma. The detachment may, however, recur if fluid continues to leak through a retinal defect in the area of the coloboma, despite internal tamponade. We present a case in which a recurrent retinal detachment associated with coloboma following vitreous surgery with SF6 was successfully repaired in outpatient surgery using perfluoroperhydrophenanthrene (Vitreon) and endolaser photocoagulation. PMID- 1508488 TI - Extreme deepening of the anterior chamber during phacoemulsification. AB - An unusual deepening of the anterior chamber during a phacoemulsification procedure was observed in 3 patients with cataracts: 1 with high myopia, 1 with a lens opacification following a vitrectomy procedure, and 1 with pseudoexfoliation syndrome. This deepening hindered emulsification of the nucleus in the posterior chamber. Early delivery of the nucleus from the capsular bag allowed phacoemulsification to proceed at the pupillary level. The "sinking" of the lens toward the vitreous cavity appears to be related to a lack of vitreous pressure due to liquefaction, or to loosening of the zonular support in the pseudoexfoliation syndrome. PMID- 1508489 TI - Ciliated respiratory-like epithelium forming cystic conjunctival lesions in a patient with Stevens-Johnson syndrome. AB - A woman with severe cicatricial conjunctival changes secondary to allopurinol induced Stevens-Johnson syndrome developed bilateral palpebral conjunctival cysts. Pathologic examination of these lesions revealed respiratory-like pseudostratified ciliated epithelium in the walls of several cysts of one eye. To our knowledge, this is the first report of this phenomenon. PMID- 1508490 TI - Bilateral dacryocystitis after punctal occlusion with thermal cautery. AB - A 61-year-old woman developed acute bilateral dacryocystitis secondary to Staphylococcus aureus 3 weeks after undergoing punctal occlusion with thermal cautery for keratoconjunctivitis sicca. The dacryocystitis resolved with intravenous antibiotics, aspiration of the lacrimal sacs, injection of sulfacetamide into the lacrimal sacs, and bilateral dacryocystorhinostomy. Preexisting bilateral nasolacrimal duct obstruction was postulated as the underlying cause. In these cases, irrigation of the lacrimal system is recommended before proceeding with punctal occlusion. PMID- 1508492 TI - Corneal light shield. PMID- 1508491 TI - Hemangiopericytoma of the lacrimal sac. AB - Hemangiopericytoma is a rare soft-tissue neoplasm composed histologically of pericytes. Hemangiopericytoma of the lacrimal sac is exceedingly rare. This case provided the first known computed tomographic image of a hemangiopericytoma of the lacrimal sac prior to surgical intervention. PMID- 1508493 TI - Phacoemulsification, foldable IOL, Holmium laser sclerostomy, and 5-FU. PMID- 1508494 TI - Comparison of digitized radiographic alveolar features between 20- and 70-year old women. A preliminary study. AB - The purpose of this investigation was to determine whether a difference exists in four digital image features, extracted from standardized periapical radiographs of the maxillary alveolar bone, between younger and older women. These features included mean pixel intensity, I(x); pixel intensity variance, var I(x); mean absolute Fourier transform coefficient, magnitude of F(u); and mean spatial first moment of the absolute Fourier coefficients, M1. The interproximal bone between the maxillary canine and lateral incisor was analyzed in two groups of 10 younger and older women with mean ages of 24 and 74 years, respectively. I(x) was significantly less in the 70-year-old group than in the 20-year-old group (p = 0.01), as were magnitude of F(u) (p less than 0.05) and M1 (p less than 0.01). Var I(x) tended to be significantly less in the 70-year-old group (p = 0.06). We conclude that in women a measurable diminution in the magnitude of these four bony features comes with age. PMID- 1508495 TI - Idiopathic bone cavity (traumatic bone cyst) with the radiographic appearance of a fibro-osseous lesion. AB - This article presents an unusual case of idiopathic bone cavity that originally was either not observed or diagnosed as a fibro-osseous condition. When a differential diagnosis was established, it included fibro-osseous conditions, odontogenic cysts and neoplasms, and central giant cell granuloma but not the definitive diagnosis. The patient's demographic data, history, symptoms, and clinical and radiographic appearance all conspired to obscure the true nature of the condition, which was not revealed until a biopsy was attempted. A more thorough initial radiographic examination might have led to an earlier diagnosis. PMID- 1508496 TI - Displaced teeth! PMID- 1508497 TI - Developmental lingual defects on the mandibular ramus. PMID- 1508498 TI - Impacted mandibular second molar. PMID- 1508500 TI - Radiographic changes to mandibular canal in osteogenic sarcoma. PMID- 1508499 TI - Golden needles. PMID- 1508501 TI - Mediastinitis caused by odontogenic infection associated with adult respiratory distress syndrome. AB - A case of descending mediastinitis resulting from dental infection and complicated by adult respiratory distress syndrome (ARDS) is reported. The patient had a long history of heavy drinking. His condition was so serious that he died despite some successful therapies. The cause of ARDS appeared to be aspiration pneumonia. It is extremely rare for oral and maxillofacial surgeons to encounter a patient with ARDS. PMID- 1508502 TI - Successful pain management by Finnish oral surgeons. A clinical follow-up study. AB - The current practice of postoperative pain management among Finnish oral surgeons was evaluated in a two-phase study. In the first phase, a questionnaire was sent to specialist members of the Finnish Society of Oral and Maxillofacial Surgeons that concerned the routine use of analgesic drugs after surgical removal of third molar teeth. In the second phase, the clinical adequacy of pain medication was assessed in 84 patients who had the same procedure. Patients estimated the intensity of pain with a 100 mm visual analogue scale at five time points during the day of surgery and on three postoperative days. Anti-inflammatory analgesics were widely used either alone or in combination with centrally acting analgesic drugs. Tolfenamic acid, diclofenac, and ketoprofen were the most commonly used analgesic drugs. The analgesic effect of the currently used drug combinations proved to be sufficient except in a few patients during the first night after surgery. PMID- 1508503 TI - Pneumomediastinum and subcutaneous emphysema associated with temporomandibular joint surgery. AB - Pneumomediastinum may occur as a result of trauma or surgery of the head and neck. It has been reported in association with various dental procedures and with a variety of maxillofacial surgical procedures. However, this potentially life threatening problem has not previously been reported in association with temporomandibular joint surgery. This report reviews two cases of pneumomediastinum and subcutaneous emphysema occurring in association with temporomandibular joint surgery and presents an overview of the dental and medical literature concerning this phenomenon occurring in association with injuries and treatment of the maxillofacial complex. PMID- 1508504 TI - Postoperative death of a patient in apparent remission of malignant lymphoma after dissection for squamous cell carcinoma. AB - A 67-year-old man in apparent remission of malignant lymphoma had squamous cell carcinoma of the left buccal mucosa. The patient underwent partial resection of the mandible, including the excision of the tumor. During the fourth postoperative night the patient suddenly became febrile and had a spiking fever for the next 5 days. His general condition deteriorated afterward, and acute aggravation of malignant lymphoma was suspected. On day 16 disseminated intravascular coagulation was indicated by a decreased platelet count of 3.8 x 10(4), a tendency toward bleeding, and multiple organ failure. The patient died 18 days postoperatively. We alert anesthesiologists and surgeons that surgically treating patients with malignant lymphoma who are receiving immunosuppressive drugs is precarious even though their disease is considered to be in apparent remission. PMID- 1508505 TI - Spontaneous fracture of hypertrophied genial tubercles. AB - A case of spontaneous fracture of hypertrophied genial tubercles is reported. This is an uncommon event with only six previously reported cases. This entity is usually associated with severe edentulous bone resorption, a condition related to the pathogenesis of this fracture. Clinical complaints include painful swelling of the floor of the mouth and impaired tongue function. If left untreated, mucosal inflammatory changes may appear and a biopsy should be performed. Total recovery is obtained after removal of the fractured fragments. PMID- 1508506 TI - Congenital fusion of the gums. AB - Congenital fusion of the gums is a rare abnormality. This is a report of a successfully treated newborn infant who had unilateral fusion of the gums. A brief review of the previously reported cases is also presented. PMID- 1508507 TI - Oral and nutritional status in allogeneic marrow recipients treated with T-cell depletion or cyclosporine combined with methotrexate to prevent graft-versus-host disease. AB - To investigate how the use of T-cell-depleted marrow or a combination of cyclosporine and methotrexate to prevent graft-versus-host disease affect oral health and the ability to maintain adequate nutrition during the neutropenic phase after allogeneic bone marrow transplantation, 48 allogeneic bone marrow recipients were studied. From a group of adult leukemic marrow recipients of HLA identical sibling marrow, 23 patients were randomly chosen to receive T-cell depleted marrow and 25 were selected to receive cyclosporine and four doses of methotrexate to prevent graft-versus-host disease. Before the transplantation, all patients were given all necessary dental treatment as well as oral hygiene and nutrition instructions. The oral mucosal and nutritional status in all patients (except one who died) were followed from 5 days before the procedure, during the neutropenic period after transplantation, and until discharge from the hospital. The number of oral lesions was similar in both groups. The subjective experience of orally related problems, such as pain from the oral cavity and number of days with total parenteral nutrition, was less in the T-cell-depleted recipients compared with those who received a graft-versus-host disease prophylaxis with cyclosporine and methotrexate (p less than 0.005). The oral cavity was considered to be the port of entry in four of six patients in the cyclosporine and methotrexate group who developed septicemia, compared with only one of six patients in the T-cell-depleted group with septicemia. The difference in the frequency of septicemia derived from the oral cavity did not, however, reach the significant level.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1508509 TI - Mucous membrane pemphigoid. Treatment experience at two institutions. AB - The initial oral findings and treatment in 50 cases of mucous membrane pemphigoid are presented. Histologic and immunologic studies were undertaken in each case to confirm the clinical diagnosis. The treatments prescribed are summarized and illustrate that topical steroids are effective, but in some cases systemic steroid therapy with or without other immunologically active drugs is required. A significant number of patients had extraoral manifestations of the disorder. PMID- 1508508 TI - Oral candidosis. Clinical, historical, and therapeutic features of 100 cases. AB - Oral candidosis is an increasingly important disease that affects a significant percentage of the population. Traditionally known as an opportunistic pathogen, the broader clinical scope of oropharyngeal candidal infections is now being recognized. The clinical and historical features of 100 patients referred for diagnosis and management of candidosis have been reviewed. The age, gender, chief complaint, medical history, medications, and clinical findings have been noted. A wide range of clinical signs and symptoms, and the rationale behind the topical and systemic antifungal therapies provided to this patient population, are discussed. PMID- 1508510 TI - Oral presentation of pemphigus vulgaris and its response to systemic steroid therapy. AB - This article reviews our experience during a 20-year period with patients with oral lesions of pemphigus vulgaris. Of the 30 patients, 20 were women and 10 were men, with an age range of 24 to 68 years. The soft palate was involved in 80% of cases at initial presentation. Direct immunofluorescence studies were positive for IgG in the intercellular region in all cases where lesional tissue was histologically studied. Systemic steroid therapy alone controlled the disease in 24 patients, one patient was given no treatment, and the remaining five required additional treatment with either azathioprine, cyclophosphamide, or gold. Steroid therapy was continued in the long-term at a reduced dose, but side effects such as diabetes mellitus, hypertension, and duodenal ulcers were observed. Long-term steroid therapy is therefore the treatment of choice for the oral lesions of pemphigus vulgaris, but in some cases alternative treatment options may be required. PMID- 1508511 TI - Prevention of malodor from intraoral gauze tamponade with the topical use of clindamycin. AB - Azulene ointment with a small dose of clindamycin was used topically in eight patients with maxillary cancer with the intent to inhibit the malodor that originates from a gauze tamponade applied to the postoperative maxillary bony defect. The malodor was either markedly decreased or eliminated in all cases. Concurrent with the decrease or elimination of the malodor, anaerobic microorganisms such as Bacteroides and Peptostreptococcus, which are considered to be involved in the generation of malodor, also became undetectable. PMID- 1508512 TI - Human ameloblastoma tumors express the amelogenin gene. AB - Instructive signals are responsible for the regulation of the expression of gene products characteristic of many cell lineages during normal development and potentially during neoplasia. The odontogenic origin of ameloblastomas is based largely on the similarity in histologic appearance between the tumor and the developing tooth organ. A pathognomonic pattern for odontogenic tissue-specific gene expression in ameloblastomas has not been previously shown. In these studies, the gene expression parameters for human ameloblastomas have been characterized with the techniques of messenger RNA phenotyping in combination with Northern and in situ hybridization analysis of messenger RNA. The results of these studies confirm that amelogenin, a gene transcribed solely by differentiated ameloblasts, was expressed by epithelial cells from human ameloblastomas. This observation suggests that the instructive signals required for ameloblast differentiation are shared during normal development and tumorigenesis of odontogenic epithelium. PMID- 1508513 TI - Ankylosis of the temporomandibular joint. Follow-up of thirteen patients. AB - We undertook a postoperative clinical study of 13 patients with ankylosis of the temporomandibular joints. The study consisted of an evaluation of the surgical concepts of resection and subsequent surgical reconstruction by osteotomy in previous height of the joint space and lining of the glenoid fossa with lyophilized dura. Early mobilization and aggressive physiotherapy are mandatory postoperative measures. According to the theory of mandibular growth as a result of functional matrix, early surgical intervention to correct ankylosis should be performed, regardless of the age of the patient, to prevent recurrence and later asymmetry or distoclusion. PMID- 1508514 TI - Clinical, historic, and therapeutic features of aphthous stomatitis. Literature review and open clinical trial employing steroids. AB - The clinical and historic features of 50 patients with diagnosed aphthous stomatitis and treated with topical triamcinolone acetonide, 0.1% or 0.2% aqueous suspension; alone or in combination with initial burst therapy of 40 to 60 mg of prednisone, are reviewed. The mean age of our patients was 36.6 years (range 6 to 80 years). The duration of the chief complaint, usually oral pain, or more specifically, recurrent oral ulcers, was 11.1 years (range 4 weeks to 40 years). All patients showed a wide range of ulcer sizes when examined initially or at follow-up. Forty were followed up for an average of 22.9 months. Thirty-four reported prompt healing of ulcers identified at the time of initial evaluation, and no or markedly fewer ulcers subsequently if maintenance therapy of prophylactic topical triamcinolone, 0.1% or 0.2% aqueous rinse, was used. Five patients reported partial relief. No systemic side effects were noted even after long-term topical therapy. Local candidosis was a complication encountered in five patients. PMID- 1508515 TI - Rough hypoplastic amelogenesis imperfecta with follicular hyperplasia. AB - This report documents a unique case of rough hypoplastic amelogenesis imperfecta with apparent anterior oligodontia and multiple anomalies of the associated mesenchymally derived tissues. Multiple unerupted teeth showed hypercementosis, distorted roots with aberrant dentin formation, and marked follicular hyperplasia. The hyperplastic follicles had a complex histopathologic appearance that recapitulated some features of the WHO-type odontogenic fibroma. The features of these teeth, the nature of the associated follicular lesions, and their relationship to the unerupted teeth are discussed. PMID- 1508516 TI - Microdontia, hypodontia, short bulbous roots and root canals with strabismus, short stature, and borderline mentality. AB - A case of unusual dental findings associated with mild growth and mental retardation is presented. The patient, a 15-year-old girl, manifests small teeth with peculiar short bulbous roots and roundly widened root canals, congenital absence of permanent teeth, strabismus, short stature, and borderline mentality. PMID- 1508517 TI - Fractal dimension from radiographs of peridental alveolar bone. A possible diagnostic indicator of osteoporosis. AB - The purpose of this study was to investigate whether a radiographic estimate of osseous fractal dimension is useful in the characterization of structural changes in alveolar bone. Ten dry mandibular bone segments were radiographed from three controlled projection angles (-5, 0, +5 degrees), before and after acid-induced partial decalcification. Fractal dimension was estimated by regression analysis of power spectra computed by Fourier transform of selected regions of interest in digitized images of the radiographs. Repeated-measures ANOVA showed that fractal dimension so determined varied over anatomic locations (p less than .01), but increased after acid-induced demineralization (p less than .0005), irrespective of the radiographic projection angles (p greater than .99). In vivo fractal dimension was computed from randomly selected intraoral radiographs of six premenopausal (ages, 32.8 +/- 3.9) and six postmenopausal (ages, 62.5 +/- 4.1) women. A significantly (p less than .01) higher fractal dimension was observed in the older group. PMID- 1508518 TI - Reduction of the compact and cancellous bone substances of the edentulous mandible caused by resorption. AB - Examination of various bone sections of edentulous atrophic mandibles showed that the body of the mandible loses up to 60% of its original bone substance during progressive atrophy. Most of the bone loss occurs in a relatively early stage of the atrophic process. The greatest extent of bone reduction can be observed in the area of the second premolar and the first molar. In the interforaminal region, which is situated mesial from them, resorption, in most cases, is not as progressive as in the premolar/molar area. The compact and cancellous bone substances are most often equally affected by resorption. Moreover, it could be observed that the cancellous bone substance of extremely atrophic mandibles particularly in the interforaminal region, is marked by a significant increase in density. This might be interpreted as a restructuring process to compensate for bone losses and to secure the stability of the atrophic body of the mandible. PMID- 1508519 TI - Measurement of the heat of reaction transmitted intracranially during polymerization of methylmethacrylate cranial bone cement used in stabilization of the fossa component of an alloplastic temporomandibular joint prosthesis. AB - Temporomandibular joint alloplastic fossa replacements have always been difficult to stabilize because of the variability of the anatomy in the area both in normal and especially in pathologic states. Total joint reconstruction and stabilization in orthopedic surgery have been aided by the use of methylmethacrylate, which is used both as a cementing substance and as a filler material when there are voids between the implant and the basilar bone. The concept of the use of a filler material to aid in the stabilization of the alloplastic temporomandibular joint fossa is attractive, but of concern because of the exothermic reaction this material undergoes as it sets in proximity to the middle cranial fossa. This study was designed to measure the temperature gradient that exists in such a procedure when used with cadaver specimens. The results indicate that the heat of reaction was not significantly transmitted intracranially in the cadavers studied. However, I recommend care in the use of this material for this purpose with patients. PMID- 1508520 TI - Clinical symptoms of open lock position of the condyle. Relation to anterior dislocation of the temporomandibular joint. AB - Nine cases of open lock position of the condyle of the temporomandibular joint (TMJ) are reported. In two patients recurrent dislocation of the TMJ was diagnosed clinically, and four had previous episodes of anterior dislocation. An arthrotomographic examination revealed that the condyles of the affected TMJs were located anterior to the anterior bands of the disks at an open-mouth position. An arthrographic fluoroscopic examination showed that the anterior bands mechanically obstructed the anteriorly displaced condyles from posterior movement into the articular fossae to various degrees at open-mouth position. One cause of anterior dislocation of the TMJ is thought to be fixation of the condyle in the open lock position resulting from a disturbance of a neuromuscular mechanism. In the two patients with dislocation, occlusal treatment eliminated muscular symptoms and the dislocations completely disappeared. PMID- 1508521 TI - Retrospective assessment of osteomyelitis. Etiology, demographics, risk factors, and management in 35 cases. AB - A retrospective review and analysis of the management of osteomyelitis in 35 patients at a major hospital complex has been made. In this patient population sample, trauma and odontogenic sources were determined to be the most prevalent causes of osteomyelitis of the jaws, which in the vast majority of cases affected the mandible. Alcohol and/or tobacco use was reported in at least one half of the cases surveyed. Surgical exploration and debridement were most frequently used during the treatment of these cases. The microbial causes of these lesions were most frequently mixed infections that originated from the oral cavity. Antimicrobial therapy most often used beta-lactam-bearing antibiotics, although combinations with other agents were often included. These and other data obtained through this study underscore the multifactored causes and therapeutic approaches found in osteomyelitis of the jaws. PMID- 1508522 TI - Postradiation dental extractions without hyperbaric oxygen. PMID- 1508523 TI - Burning mouth syndrome. Critical review and proposed clinical management. AB - Burning mouth syndrome is characterized by a burning sensation in one or several oral structures. Multiple causal factors have been proposed, and reports on their relative importance are conflicting. Lack of diagnostic criteria, differences in sampling procedures, incomplete workups, and lack of controlled studies make the reliable interpretation of the importance of proposed causal factors and the efficacy of specific treatment modalities difficult. This article summarizes the available data, critically analyzes their scientific merit, and proposes a protocol for clinical management. PMID- 1508524 TI - Gingival lesions of HIV infection in 178 Greek patients. AB - One hundred seventy-eight HIV-infected Greek patients were examined and the gingival lesions were recorded. At the time of oral examination, 77 patients were HIV positive, 53 had ARC, and 48 had AIDS. The mean age of the patients was 36.6 years; 158 were men and 20 were women. Fifteen different gingival lesions were recorded. Necrotizing gingivitis (10.1%), gingivitis (5.0%), periodontitis (18.5%), candidiasis (5.8%), and Kaposi's sarcoma (5.0%) were the most common lesions observed. Oral lymphomas and other lesions were recorded in low numbers. Our findings show that dentists should be aware of gingival lesions of HIV disease because some of them are common and diagnostically important. PMID- 1508525 TI - Linear IgA disease manifesting as recalcitrant desquamative gingivitis. AB - A case of desquamative gingivitis caused by adult linear IgA disease is presented. Management initially proved to be difficult, however, the introduction of sulfapyridine caused rapid resolution of the gingival problem. This is one of the first reports of desquamative gingivitis caused by linear IgA disease successfully treated with sulfapyridine. PMID- 1508526 TI - Ingestion of medication among patients with oral keratoses including lichen planus. AB - One hundred forty-nine patients attending Edinburgh Dental Hospital had oral keratosis diagnosed clinically and histologically. The keratoses were grouped into erosive and nonerosive lichen planus, other keratoses infiltrated with inflammatory cells, and noninfiltrated keratoses. Drug histories were obtained from each patient on presentation, and the groups were analyzed to assess the association between the ingestion of commonly prescribed drugs and oral keratoses. Patients with infiltrated keratoses took nonsteroidal anti inflammatory drugs twice as often as patients in the other groups, whereas those with lichen planus more frequently ingested antihypertensive drugs. Patients with erosive lichen planus were 10 times more likely to ingest nonsteroidal anti inflammatory drugs than those with nonerosive lichen planus (p = 0.01). PMID- 1508527 TI - Langerhans' cell histiocytosis in association with periapical granulomas and cysts. AB - This report describes a series of six cases of inflammatory periapical disease with small aggregates of Langerhans cells as a minor component. Immunohistochemical findings confirm that the cells are phenotypically related to Langerhans cells. Aggregates of these cells are not normally found in radicular cysts or periapical granulomas and have been interpreted to represent chronic localized Langerhans' cells histiocytosis. Whether these lesions, which arise within the context of chronic inflammatory periapical disease, represent incipient eosinophilic granulomas or are a more benign, minimally destructive form of Langerhans' cell histiocytosis is unknown. Clinical follow-up suggests that these lesions remain localized and that curettage is adequate treatment. PMID- 1508528 TI - Merkel cell carcinoma of the labial mucosa. An immunohistochemical and ultrastructural study with a review of the literature on oral Merkel cell carcinomas. AB - Merkel cell carcinoma is a rare cutaneous neuroendocrine tumor that occurs predominantly in the head and neck region of older patients. An 88-year-old white man had an erythematous, umbilicated tumor on his lower lip, which on histopathologic examination showed solid sheets of infiltrating basaloid round cells with a high mitotic index. Globular, paranuclear immunostaining for low molecular-weight cytokeratins (Nos. 8, 18, and 19) and neurofilament was observed. On ultrastructural examination, the tumor cells demonstrated paranuclear whorls of intermediate filament aggregates and occasional electron dense granules. This unique cytokeratin- and neurofilament-staining pattern with coexpression enabled the Merkel cell carcinoma to be differentiated from other small cell malignant tumors that included metastatic neuroendocrine carcinomas from other regions. The follow-up 1 year after surgery and radiation showed that the patient remained disease free. Review of the literature revealed 11 cases of oral Merkel cell carcinomas with a predilection for the labial mucosa of older men. The mode of treatment and the clinical course of these cases are also presented, with an update on therapeutic management of Merkel cell carcinomas. PMID- 1508529 TI - Desmoplastic malignant melanoma of the gingiva. AB - A case of desmoplastic melanoma in a 58-year-old man is reported. This rare malignancy occurred in the maxillary alveolus, appearing as an epulis. Histologically, the tumor was flanked by melanocytic proliferation in the adjacent mucosae. At the time of local recurrence after partial maxillectomy, the tumor showed a polypoid growth, with an increase in cellularity and mitotic rate resembling spindle cell carcinoma. The value of immunostaining for diagnosis is stressed. PMID- 1508530 TI - Follicular carcinoma with clear cell change arising in lingual thyroid. AB - A case of follicular carcinoma arising in the lingual thyroid of a 23-year-old woman is added to the 22 previous reports. The embryology and the clinical and pathologic differential diagnoses are discussed. Histologic criteria useful in diagnosing follicular malignancy in this area include local and vascular invasiveness, hypercellularity, mitotic activity, and necrosis. The use of the immunohistochemical marker thyroglobulin and electron microscopy are described for the first time and confirm a thyroid follicular cell origin. PMID- 1508531 TI - Posttraumatic spindle cell nodule of the buccal mucosa. Report of a case. AB - A benign posttraumatic spindle cell proliferation arising at a site of laceration in the buccal mucosa of a 19-year old man is described. This lesion, which histologically mimicked a leiomyosarcoma, appears to represent a reactive process similar to that described as postoperative spindle cell nodules of the genitourinary tract. Reexcision of the area 1 month after biopsy revealed only scar formation and mild chronic inflammation. Recognition of this type of benign spindle cell proliferation at traumatized sites in the oral cavity is important if misdiagnosis and subsequent aggressive therapy is to be avoided. PMID- 1508533 TI - Frequent, low-dose, improved-contrast radiographic images with the use of narrow x-ray beams. AB - Conventional dental radiography uses 60 mm-wide x-ray beams that irradiate the cheeks. To reduce the dose of radiation, months or years can separate serial films and prevent short-term assessment of disease activity. A technique that uses a 13 mm narrow x-ray beam that avoids the cheeks was compared with a wide x ray beam by using a contrast phantom, a cheek substitute, and a serially sectioned dry mandible. Phantom contrast was measured densitometrically at 50 kVp, 65 kVp, and 90 kVp with wide x-ray beam and narrow x-ray beam and with and without cheek scatter. The narrow x-ray beam without cheek scatter technique resulted in better contrast (0.06 to 0.04 OD) than the wide x-ray beam with cheek scatter (0.05 to 0.02 OD). A posterior interdental crest was irradiated and a trabecular rod was removed. The bone detail was best in the images produced with the narrow x-ray beam without cheek scatter. The area of the narrow x-ray beam was 4.35% of the area of the wide x-ray beam with approximately 5% of the dose. Short-interval (weekly), very-low-dose radiography should be possible with improved contrast to assess alveolar bone changes. PMID- 1508532 TI - Antimicrobial activity of seven root canal sealers. Results of agar diffusion and agar dilution tests. AB - A comparative study of the antimicrobial action of seven root canal sealers: Traitement Spad, Endomethasone, N2 Universal, Diaket-A, AH26 with silver, Tubli Seal, and Sealapex was done with 120 strains of Staphylococcus aureus. Two antimicrobial susceptibility tests were used: the agar dilution test and the agar diffusion test. The Diaket-A and Traitement Spad sealer cements showed the highest efficiency in the dilution test, whereas Diaket-A was in fourth place in the diffusion test, only better than the antimicrobial activity of the Tubli Seal and Sealapex sealers. PMID- 1508534 TI - The radiographic characteristics of histiocytosis X. A study of 29 cases that involve the jaws. AB - The purpose of this study was to provide an objective analysis of the radiographic characteristics of histiocytosis X as it affects the jaws. The original radiographs of 29 cases were reviewed independently and objectively by three observers. The results suggest that seven characteristics, either alone or in combination, are useful in the identification of histiocytosis X. These include the appearance of solitary "intraosseous" lesions, the multiplicity of "alveolar bone" lesions, the "scooped-out" effect in the alveolar process, the well-defined periphery, sclerosis in the alveolar bone lesions, periosteal new bone formation, and slight root resorption. PMID- 1508535 TI - Radiographic investigation of idiopathic osteosclerosis of the jaws in Japanese dental outpatients. AB - Panoramic radiographs of 1203 Japanese patients were examined to detect idiopathic radiopaque foci of dense bone. One hundred seventeen patients (9.7%) exhibited 134 such lesions. The majority (97%) of the opacities were found in the mandible, especially in the mandibular first premolar to second molar region (85.4%). The lesion was most prevalent in the first three decades of life. PMID- 1508536 TI - The clinicoradiologic predictability of perforations of the soft tissue of the temporomandibular joint. AB - One hundred thirty-one arthrographic examinations of temporomandibular joints were performed on 119 patients. The relationships between clinical symptoms, tomographic findings, and soft-tissue perforation were examined. Perforations of the articular disk or posterior attachment were revealed in 58 joints. Joints with crepitation showed a high frequency of perforation (20 of 22). Pain in the joint area and limitation of opening correlated to disk reduction. Perforations were observed in 12 of 21 joints with continuous pain. Osseous changes were detected in 89 joints. Joints with abnormal radiodensity (erosion, sclerosis) combined with abnormal shape (pocket erosion, osteophyte formation, deformity) showed a high frequency of perforation (41 of 45), which corresponded to 84% in this study. In those cases with osseous change or crepitation, positive predictive values of perforation were both 91%. These types of osseous change and their clinical significance might predict soft-tissue perforation with high accuracy before an arthrogram is performed. PMID- 1508537 TI - Unusual appearance of mental foramen on panoramic radiograph. PMID- 1508538 TI - [Results with endoprostheses and bone transplantation in surgery for bone tumors]. AB - Seventy six bone tumor patients were treated by limb salvage operations at the Orthopaedic Department of the Semmelweis Medical School in Budapest from 1981 through 1991. The bone defect was reconstructed with endoprostheses in 25 cases and with bone grafts in 51 cases. The mean follow-up period of 72 patients was 51 months (min. 12 months). There were local recurrences in 11% of the patients. Two complications occurred at the tumor endoprostheses, which functional rating were excellent or good in 75%. The most common complications at the bone grafting were infection (9.8%), fracture (11.8%), which did not influence the end result, and nonunion (9.8%) occurring often in homografts of resection-arthrodesis during the chemotherapy. This complications could be managed in all but two cases without loss of the limb. The bone grafts performed acceptable (excellent or good) functional result in 66% of the patients. Authors suggest reconstruction of the bone defect with bone grafting in cases of semimalignant and low malignant tumors, prefer, however, tumor endoprosthesis implantation in high malignant bone tumors which need chemotherapy. PMID- 1508539 TI - [Retinal microangiopathies in diabetic children and adolescents, occurring in cases of pubertal and prepubertal onset of diabetes]. AB - The prevalence and development of retinal microvascular complications in pre puberty and puberty onset insulin-dependent diabetes mellitus were studied in 109 young patients with an average follow-up of 6 years. The data suggest that the earlier childhood the diabetes began, the later the microvascular abnormalities could be found by fluorescein angiography. First signs of background retinopathy were seen in average 20--22 years of age, almost independently the age at onset of diabetes. Rapid progression of retinal vascular damage occurred mainly in postpubertal but not pubertal subjects. Diabetes with puberty onset meant worse prognosis in the respect of retinal vascular complications than pre-puberty onset. Good glycemic control would be achieved more difficult in subjects with puberty onset diabetes added to a changing hormonal balance. The authors suggest that psychological factors (altered behavior during and after puberty) and other problems of adolescents (changes in social, familial and working conditions) may also contribute to poor glycemic control. Though the effect of prepubertal duration on the risk of retinal complications appears to be smaller than later years, the attendant work in prepubertal years is as important as later. PMID- 1508540 TI - [Changes in melatonin blood levels during gonadotropin releasing hormone loading tests in women with anovulatory disorders]. AB - The results of seven gonadotropin releasing hormone (GnRH) loading tests are presented with special respect to the changes of melatonin level. The tests were carried out after a withdrawal bleeding triggered by progesterone (100 mg for 5 days) and plasma FSH, LH, prolactin and melatonin level were determined. The initial melatonin values were between 3.9 and 35.7 pg/ml and were in inverse ratio with the basal gonadotropin levels. In the case of reactive hypophyseal response the melatonin level decreased in every case in inverse ratio with the increase of gonadotropins. In one case, after the GnRH administration there was no increase in gonadotropin production and at the same time the melatonin secretion remained unchanged. According to our examinations the melatonin secretion during the GnRH loading test showed a good correlation with the changes of gonadotropins. PMID- 1508541 TI - [Diagnostic possibilities of endoscopic ultrasonography in the detection of gastric cancer]. AB - After conventional gastroscopy and biopsy the endoscopic ultrasonography (EUS) was performed in 115 patients with gastric ulcer and carcinoma. The markers of benignity and malignity were analyzed by EUS, and the criteria of benign and malign excavated lesions were described. On the base of endoscopic pictures 3 groups of gastric excavations were distinguished, and the recorded images of this excavations were reevaluated. Benign ultrasonic markers were detected in one case of excavated tumors, in 54% in group of ulcers with suspicion of malignity and in 82% in cases of benign ulcers. Authors evaluate the cause of overestimate. Ten cases of early gastric cancers are reported. Authors believe that the endosonographic examinations of the stomach are valuable in detecting and stating of gastric carcinoma. PMID- 1508542 TI - [Hemorrhagic shock and encephalopathy]. AB - Levin et al. described a new syndrome called haemorrhagic shock and encephalopathy in 1983. The authors present a case report and give an overview about the disease. They summarize the informations published recently. PMID- 1508543 TI - [Arpad Gotze, M.D. (1891-1977)]. PMID- 1508544 TI - [Centenary of the foundation of the first Association for Physiological Sciences in Hungary]. PMID- 1508545 TI - [Compensation in leg length inequality with orthopedic shoe measures]. AB - There are three different methods of compensating for differences in leg length. The first is the construction of special shoes, which is adequate for differences of up to about 3 cm. The heels can be either higher or lower, or a cork sole 5-10 mm thick can be incorporated, the shaft made higher, and supplementary features, such as aids to push-off, can also be implemented. The second method is the wearing of the classic orthopedic boot or shoe, in which the necessary compensation for the shorter leg is incorporated as a part of the orthopedic footwear. The third method is the construction of a shoe within a shoe, for which different designs have crystallized out for the five groups presented. All designs incorporate leather, the tried and tested material, next to the skin. Stabilizing components are made of fiberglass-reinforced synthetic resin or Thermoplast. New materials allow aesthetically acceptable orthopedic footwear. On average, such shoes are 25% lighter than conventional orthopedic boots. The stability and wear-resistance allow large perforations and open-toe designs, which has made it possible to solve the problem of ventilation. PMID- 1508546 TI - [Technical orthopedic compensation of leg length inequality]. AB - The objectives and limitations in the prescription and construction of leg length adjustments are reviewed. The functional and structural significance of differences in leg length for patients and for healthy persons in different age groups and in different growth phases is considered. A few unconventional ideas, and some information and personal and environmental characteristics are described, leading to a discussion of care criteria that go further than the more usual care systems. It is stressed that interdisciplinary care makes it absolutely essential to note what system of measurement is being used when the treatment is prescribed. Attention is drawn to the possibility of using electrophysiological measurements--whether in the doctor's or physiotherapist's practice or in the orthopedic workshop--for monitoring. Unchanged biomechanical and orthopedic positions are shown in sketches. PMID- 1508547 TI - [Ilizarov techniques of leg lengthening. Problems and results]. AB - Leg lengthening procedures have developed rapidly in the last 20 years, especially distraction epiphyseolysis and corticotomy. We have used both methods since 1977 and carried out 22 distraction epiphyseolyses (20 patients) and 33 corticotomies (28 patients). The average lengthening distance was 8.25 cm and 7.8 cm respectively (minimum 4 cm, maximum 18 cm). The time per cm lengthening (lengthening index) was 45.8 days/cm for epiphyseolysis and 52.2 days/cm for corticotomy. The complication rates were similar in both methods (1.18 and 1.21 pro lengthening procedure). Both techniques are preferably performed by a well trained team of physicians, nurses and physiotherapists for correction of leg length discrepancies. PMID- 1508548 TI - [Limb lengthening with epiphyseal and callus distraction using the Wiesbaden ring fixator]. AB - Treatment of unequal leg-length can either be operative or conservative. The historical development and devices for ring fixation are discussed. The surgical technique is described in detail along with the post-operative care in cases of epiphyseal distraction and callus distraction with a ring fixator. The article closes with the advantages of the method and its possible complications. PMID- 1508549 TI - [Problems and complications of leg lengthening with the Wagner apparatus]. AB - Since 1971, we have performed 189 leg lengthening procedures using the Wagner method at our institution. The results obtained in the first 26 cases (1971-1973) showed a high complication rate, which led us to reconsider the indications for this procedure. In the present paper, we analyze the results of 37 leg lengthening procedures carried out in 32 patients during the last 10 years (1981 1990) in the children's unit of the orthopedic department of the University of Basle. We found a complication rate of 78%, and in 46% of cases there was more than one major complication. We did not distinguish between "complications" and "problems", because such distinctions are of little importance to the patient. The average age at the time of surgery was 14.8 years, and the average increase in length was 4.3 (2.2-9.2) cm. For each 1 cm of lengthening, an average of 21 days in hospital and 64 days of reduced weight-bearing were needed. Our conclusion is that the Wagner method makes it possible to attain the goal of leg lengthening, but the second step cannot reduce the length of stay in hospital or the length of time the patient needs the help of crutches. Bone remodeling is disturbed. Our preliminary experience with the Ilizarov method is more encouraging. PMID- 1508550 TI - [Lengthening osteotomy of radius and ulna in malalignment of the elbow or wrist joint]. AB - The solitary shortening of radius or ulna gives rise to malalignment of the wrist or elbow. Shortening of the ulna causes dislocation of the head of radius, shortening of the radius leads to a clubhand with disorders of the wrist. The disphyseal lengthening osteotomy of the radius or ulna corrects these deformities. PMID- 1508551 TI - Clinical psychopharmacologic trials help patients with anxiety/depression. PMID- 1508552 TI - Helene Fuld Health Trust awards $2.1 million for a nursing information exchange. PMID- 1508553 TI - Registered nurses' nonparticipation in continuing professional education. PMID- 1508554 TI - Re-evaluation of clinical experiences to empower nurses as leadership. PMID- 1508555 TI - Life and death choices: living wills and powers of attorney. PMID- 1508556 TI - Practice consultation: what is it? PMID- 1508557 TI - Pressure ulcers in adults. PMID- 1508558 TI - Questions & answers about AIDS. PMID- 1508559 TI - The hyperflexed seemingly useless tetraplegic hand: a method of surgical amelioration. AB - In a series of 65 tetraplegic hands with severe disabling spasticity and/or flexion contracture, selective flexor tendon elongation procedures were employed to improve their static and kinetic postures. A kinetic approach was adopted, utilizing local anesthesia in a wide-awake patient. This was employed to allow for the patient's cooperation in determining at surgery the desired length of digital extension at the time of wrist tenodesis action. Elongation of the extensor digitorum communis (EDC), extensor indicis proprius (EIP), and extensor digiti quinti (ED V) were added to correct an 'extrinsic-plus' posture observed in 16 patients following flexor tendon lengthening. With the resultant improvement in the static posture of the digits, tendon transfers could then be employed to provide a more functional tenodesis action. These measures provided both improved palmar contact and prehension. PMID- 1508560 TI - Effects of functional electrical stimulation (FES) on evoked muscular output in paraplegic quadriceps muscle. AB - In order to assess the effects of FES on muscle output, chronic electrical stimulation of the quadriceps muscle was applied for half an hour twice a day for 2 months, in 10 thoracic level traumatic paraplegic patients. Results concerning torque (at 6 different muscle lengths) and fatigue were measured using a strain gauge transducer in isometric condition, and compared with the findings in 15 paraplegic patients who had not received electrical stimulation, and with 10 able bodied subjects with normal motor functions. With training, muscle strength was very significantly improved whilst fatigue resistance remained at a low level. The peak torque was not found to be of the same muscle length when comparing paraplegics and control subjects; it seemed to demonstrate that length-tension relationship of the muscular actuator was changing when it was electrically activated. Moreover, the force recorded in paraplegics remained markedly lower than in able bodied people. PMID- 1508561 TI - Reduction of seating pressure using FES in patients with spinal cord injury. A preliminary report. AB - The aim of this study was to investigate the use of functional electrical stimulation (FES) as a means of pressure sore prevention in seated spinal cord injured (SCI) subjects. Nine SCI subjects took part in tests in which electrical stimulation was applied to the quadriceps with the lower legs restrained. Ischial pressures were measured during periods of quiet sitting and FES application. A strain gauged lever arm was used to measure the knee moment during quadriceps stimulation. The average pressure drop at the right and left buttocks was 44 mmHg and 27 mmHg respectively. In general the greatest reductions occurred in subjects with larger knee moments; however, there was no direct relationship between the pressure reduction obtained and the quadriceps strength. This form of FES may be useful as a prophylactic aid in the management of pressure sores in SCI subjects. PMID- 1508562 TI - Breathing pattern adjustments during the first year following cervical spinal cord injury. AB - The alterations in lung function and breathing pattern were examined in 6 quadriplegics at 3, 6 and greater than 12 months post injury, and were compared to 6 able bodied controls. Subjects were studied in both the seated and supine positions. Functional residual capacity (FRC), forced vital capacity (FVC), inspiratory capacity (IC), and maximum mouth pressure (Pimax) at FRC were measured. Total lung capacity (TLC) and residual volume (RV) were calculated. Resting breathing pattern was assessed for 20 minutes from a spirogram derived from summed rib cage and abdominal strain gauge signals. At 3 months in quadriplegics, TLC was reduced (p less than 0.05), RV increased (p less than 0.01) and FRC was normal in sitting; in supine, only TLC was reduced (p less than 0.05); Pimax was decreased (p less than 0.01) in both positions in quadriplegics at 3 months, but increased over the first year in the seated position (p less than 0.01). There were no alterations in breathing pattern at any time interval in quadriplegics in supine. In contrast, at 3 months post injury in sitting, expiratory time (Te) was shortened (p less than 0.05), tidal volume (Vt) was decreased, and heart rate elevated as compared to controls (p less than 0.05). Inspiratory time (Ti) was not significantly shortened at 3 months in quadriplegics, but a lengthening of Ti occurred between 3 and 6 months (p less than 0.025) resulting in increased Vt, and heart rate decreased to normal. Vt/Ti was reduced, and did not alter with time. The lengthening of Ti/Ttot observed in supine in control subjects (p less than 0.025), was not observed in quadriplegics. Quadriplegics sighed as frequently in supine as did controls at all stages post injury, whereas they decreased sighing frequency in sitting at 3 and 6 months post injury (p less than 0.05). The improvement in resting breathing pattern observed in quadriplegics in sitting with time, may be due to increased accessory muscle function, improved chest wall stability and thoracoabdominal coupling, or a combination of these factors. It is also possible that the alterations in breathing pattern were a response to cardiovascular adjustments occurring in the same time frame. Quadriplegics retain the sigh reflex, but do not take as many big breaths in sitting as they do in supine, probably due to the increased work of breathing in the seated posture. PMID- 1508563 TI - An investigation of the relationship between environmental factors and job satisfaction in intensive nursing, with particular reference to spinal trauma. AB - The literature concerning the effects of stress on health service professionals has increased rapidly over the past 10 years (eg Holland et al, Koran et al, Stone et al). The potential sources of such stresses are briefly reviewed and the involvement of the working environment as a source of stress is highlighted. The present investigation has examined the experience of 3 groups of nurses, working in spinal injuries, head injuries, and general medicine, using a standardised questionnaire devised by Moos. Significant differences were found between the 3 nurse groups on 3 subscales of the test (autonomy, innovation, and comfort), and the implications of the findings are discussed. PMID- 1508564 TI - The algesic syndrome in spinal cord trauma. AB - This article represents the author's experience in the diagnosis and management of pain in patients with spinal cord injuries, and describes methods applied to objectively evaluate pain syndromes and different surgical procedures to alleviate such pain. Instrumental methods for pain relief are also briefly discussed. PMID- 1508565 TI - Short-latency somatosensory evoked potentials (SSEPs) of the tibial nerves in spinal cord injuries. AB - Stimulations of the tibial nerves of 76 spinal cord injured patients revealed short-latency somatosensory evoked potentials (SSEPs) especially P37 recorded from the scalp. The SSEPs findings can be classified by degrees of impairment into 5 different types as follows: Type 1: Absence of P37. This was found in all patients with complete cord lesions as well as patients with loss of joint sense. Type 2: Decreased amplitude and prolonged latency. This was elicited in patients with moderate to severe central cord lesions. Type 3: Prolonged latency only. Type 4: Decreased amplitude only. Type 5: Normal P37, which was mostly seen in patients with mild central cord lesion. The study demonstrated that SSEPs of the tibial nerves are related to joint sense and seem to relate to the extent of cord damage, especially of central cord and complete cord lesions. It can be done as early as during the first week post injury, particularly in an uncooperative patient suspected of having spinal cord injury, in which case the clinical assessment may be difficult and unreliable. PMID- 1508566 TI - The measurement of muscle tone. AB - Neurophysiologists have long been interested in phenomena associated with the activity of single nerve cells and much that has been found out has some implication for the management and understanding of spinal injuries. Others have been more concerned with integrative aspects, and it is with one aspect of this work that I am now concerned. PMID- 1508567 TI - A comparative study of the muscle strength and mass of the arm flexors and extensors in paraplegic and in non paraplegic basketball players. AB - OBJECTIVES: to study the changes in the strength of the elbow flexors and extensors in paraplegic subjects, and the agonist/antagonist mass and strength ratio in paraplegic wheelchair users. METHOD: 10 paraplegic wheelchair basketball players were compared with 10 healthy basketball players. The 20 subjects underwent a clinical and dynamometric isokinetic assessment, and a CT scan measurement of the muscle cross-sectional surface area of the flexor and extensor muscles of the elbows. RESULTS: there was an increase in muscle strength in paraplegic subjects. There was no significant difference in the agonist/antagonist ratio between the dominant and non dominant upper limb in paraplegics whereas such a difference was found in healthy subjects. The muscle mass was increased in the paraplegics, but a correlation between muscle mass and strength was only found in the healthy subjects. PMID- 1508568 TI - Primary multiple spinal extradural hydatid cysts. Case report and review of the literature [corrected]. AB - In this paper a patient with primary multiple extradural hydatid disease is described. He had no neurological deficits, although there were numerous hydatid cysts located at the thoracic 7-9 level extradurally. Nuclear magnetic resonance (NMR) was used for what would appear to be the first time for the diagnosis of spinal hydatid disease. PMID- 1508569 TI - The older adult with a spinal cord injury. AB - Sixty-two consecutive acute spinal cord injury (SCI) patients who were aged 55 years or older were studied and compared to 296 SCI patients of age less than 55 years. Compared to younger patients, the older group had significantly more females (29%), preexisting medical conditions (87%), associated injuries (55%), incomplete quadriplegic patients (63%), and persons whose injuries resulted from falls (53%). There were no differences between groups in frequency of ventilator use, occurrence of medical complications, or acute length of stay, but older patients tended to have fewer surgical spinal fusions (40%), shorter rehabilitation stays (66.5 days), more indwelling urethral cathteters (31%), and more nursing home discharges (19%). With other factors being controlled, advancing age was predictive only of nursing home discharge, and not of acute or rehabilitation lengths of stay. Among older SCI patients, those with complete injuries were nearly 3 times as likely to have been discharged to nursing homes in our series compared to older patients with incomplete lesions. Although many aspects of the presentation, course, and care of older SCI individuals are similar to those of younger patients, there are several unique features of older adults with a SCI. PMID- 1508570 TI - Pregnancy in a quadriplegic patient treated with continuous intrathecal baclofen infusion to manage her severe spasticity. Case report. AB - A report on pregnancy in a quadriplegic patient treated with a high dose of 1000 mcg/24 h continuous intrathecal baclofen infusion using an implanted drug delivery system (Synchromed, Medtronic, USA). Spasticity could be managed up to the 35th week of gestation. However, uterine contractions evoke enormous spastic symptoms which we, even with maximum values of the spasticity scales, could not classify. The recurrence of spasticity was associated with autonomic dysregulation. With continuous epidurally infused bupivacaine (11.25 mg/h) adequate relaxation could be reached and gestation was terminated by a primary caesarean section. A healthy girl was born (2040 g, Apgar 9 and 10). PMID- 1508571 TI - A pediatrician's view. Doom and gloom again--what we can do about it. PMID- 1508572 TI - Cholesterol mania. PMID- 1508573 TI - Commentary on child abuse and neglect. PMID- 1508574 TI - The diagnosis of inflicted injury in infants and young children. PMID- 1508575 TI - The care of alcohol- and drug-affected infants. AB - When addicted families remain untreated, infants and children born into and raised by these families are at high risk of abuse and neglect. Early intervention appears to mitigate neurodevelopmental damage caused by drugs and alcohol. It is unclear whether the high risk of abuse and neglect in these families can also be modified. Early intervention and ongoing supervision may be costly, but the long-term costs will be much higher if the multigenerational cycle of both diseases is not broken. A multidisciplinary team approach is essential to free children from the double burden of substance abuse and its frequent consequence, child abuse. PMID- 1508576 TI - Sexually transmitted diseases and child abuse. AB - The diagnosis in a child of any infection that is usually sexually transmitted in adults should raise the suspicion of possible sexual abuse. We know sexual abuse is a common childhood experience. The American Academy of Pediatrics Committee on Child Abuse and Neglect has rated the implications of sexually transmitted diseases for diagnosing sexual abuse (Table 6). PMID- 1508577 TI - Child abuse in a sea of neglect: the inner-city child. PMID- 1508578 TI - Is there a role for the child psychiatrist on child abuse teams? PMID- 1508579 TI - Radiological assessment of the effects of splinting on early hip development: results from a randomised controlled trial of abduction splinting vs sonographic surveillance. AB - Whilst delayed treatment of fully dislocated hips diagnosed at birth prejudices final outcome, splinting clinically dislocatable hips is controversial as the majority stabilise spontaneously. Early stabilisation may not ensure normal development but even early splinting carries a small risk of avascular necrosis. We report radiological data from 76 newborns with dislocatable hips that were randomised either to immediate splinting or to sonographic surveillance which examines the influence of early splinting on hip development. Epiphyseal maturation (EM), iliac indentation (II) and acetabular angle (AA) were assessed radiographically at 6 months, blind to the treatment group; hips with normal sonograms at birth had greater EM and II and smaller AA. Whilst clinically unstable Graf type 1 and 2A hips were radiologically similar at 6 months, those splinted showed poorer EM and II compared with non-splinted hips. There were no cases of avascular necrosis. Abduction splinting may displace the femoral capital epiphysis medially resulting in poorer iliac indentation. The smaller epiphysis in splinted infants may be secondary to altered blood supply due to increased pressure between the femoral head and acetabulum and increased tension of the adductor muscles in the thigh. These differences were less marked by 1 year. Whether they have any long-term significance requires further study. PMID- 1508580 TI - Renal transplant hemodynamics in children: prospective analysis of colour coded versus pulsed Doppler sonography. AB - In 30 children with renal allografts the diagnostic validity of pulsed Doppler (PD) versus colour coded Doppler (CD) sonography was assessed prospectively. 46 PD examinations were performed calculating the resistive index (RI) in the segmental arteries in comparison to 46 CD scans, where renal blood flow throughout the grey-scale image was displayed. In addition, point-spectral analysis with calculation of the RI was also performed on the CD scans. The time for examination ranged from five to ten minutes for the PD and from three to five minutes for the CD study. Concordant findings for the PD and CD technique were generally obtained (normal blood flow pattern on PD-excellent visualization of renal blood flow on CD, reduced or reversed diastolic flow on PD-poor visualization of renal blood flow on CD). There was close correlation of the RI values obtained by the PD and CD scans. CD sonography facilitated point-spectral analysis in shortening the time for examination. The ability to visualize focal hemodynamic alterations provided a higher diagnostic accuracy in comparison to PD sonography. PMID- 1508581 TI - Therapeutic use of surfactant in neonatal respiratory distress syndrome. Correlation between pulmonary X-ray changes and clinical data. AB - As part of a multicenter surfactant rescue study, the chest X-rays of 239 preterm and term infants were analyzed. To study the influence of surfactant administration on radiographic appearance, 130 patients with a clinical and radiological diagnosis of typical respiratory distress syndrome were selected, in whom adequate chest x-rays before and within 48 h after treatment were available. Median gestational age was 30 weeks (range 25-38 weeks), median birth weight was 1335 g (range 625-3450). The time of surfactant application ranged between 90 min and 24 h after birth (median 6 h). The most common finding after surfactant administration was uniform (n = 47) or disproportionate (n = 46) improvement of pulmonary aeration, which showed a significant correlation to posttreatment reduction of oxygen requirement (p less than 0.0001). Asymmetric clearance was more often localized on the right side and usually disappeared within two to five days. Only in 13 patients no change of ventilation was found. Development of interstitial emphysema (n = 24, including three patients with pneumothorax) after surfactant treatment was an unfavourable prognostic sign. 54% of these patients (13 of 24) died within the first month of life, compared to 8% (7 of 93) in the group of patients with initial improvement of ventilation. PMID- 1508582 TI - High resolution ultrasound with Doppler: a diagnostic adjunct in orbital and ocular lesions in children. AB - Twenty-six infants and children with orbital and ocular pathology were examined with ultrasound (US) utilizing real-time imaging and Duplex Pulsed Doppler evaluation. Twenty-two of these patients underwent concurrent orbital computed tomography (CT) and two had magnetic resonance imaging (MRI). Orbital and periorbital lesions included hemangioma, dermoid, lymphangioma, rhabdomyosarcoma, encephalocoele and abscess. Ocular lesions included infection, trauma, retinal detachment, retinoblastoma, Coat's disease, and persistent hyperplastic primary vitreous. High resolution US with Doppler provided unique diagnostic information in patients with penetrating ocular trauma, orbital and periorbital masses, and intraocular structural abnormalities. High resolution US examination of the eye and periorbital tissues is readily performed using widely available equipment and often delineates subtle structural abnormalities not shown by CT or MRI. PMID- 1508583 TI - Colour Doppler imaging of intracranial vasculopathy in severe infantile sialidosis. AB - Neonatal ascites is usually attributed to prenatal infections, lysosomal storage disease and anomalies of the genitourinary tract, gastrointestinal tract or cardiovascular system. We report one case of neonatal ascites associated with infantile sialidosis. Cerebral sonography showed stripe-like intracerebral echogenicities in the region of the basal ganglia. Colour Doppler imaging demonstrated blood flow within the echogenicities confirming the suspected diagnosis of intracranial vasculopathy. PMID- 1508584 TI - Hyperechoic lesions in the basal ganglia: an incidental sonographic finding in neonates and infants. AB - Cerebral ultrasound (US) imaging was performed as a screening procedure in approximately 3,600 neonates and infants over a period of 18 months. Hyperechoic lesions in the basal ganglia and thalamic region were detected incidentally in 15 of these patients. Clinical diagnoses included cytomegalovirus infection, asphyxia, rotavirus infection, prematurity, amniotic infection, dysmorphic stigmata, hyperbilirubinemia, congenital heart disease, and diabetic fetopathia. Lesions showed a single punctate (n = 5), multiple punctate (n = 8), or stripe like pattern (n = 2), with no disease-specific distribution. Computed tomography performed in two of the 15 patients was normal. Lesions resolved within four to seven months in four of eleven cases who had follow-up studies, whereas echogenicities persisted in the remaining seven patients over a period of observation ranging between one to 15 months. Our results indicate that hyperechoic lesions in the basal ganglia and thalamic region may be associated with congenital infections and asphyxia, but could indicate some other unknown pathology. No correlation was found between the morphology of foci and both clinical diagnosis and results of follow-up studies. PMID- 1508585 TI - Delayed presentation of congenital diaphragmatic hernia. AB - Eight patients aged 1 month up to nine years with congenital diaphragmatic hernias (seven left sided postero-lateral, one right-sided antero-medial), who presented outside of the neonatal period, are reported, four are described in detail. Radiographic presentation was obvious in four patients, simulated inflammatory lung disease in one and pneumothorax in two. In one patient a Morgagni hernia was primarily missed. Two had previous normal chest X-rays. All cases with herniated bowel showed "connecting" bowel segments passing through the diaphragmatic defect. Primarily the lack of awareness of delayed presentation of congenital diaphragmatic hernia in children with uncharacteristic thoracic and/or abdominal symptoms led to an undesirable time delay between first chest X-ray and surgery up to 16 months in four of our cases. Life threatening complications can be the consequence of delayed diagnosis as in one of our cases. PMID- 1508586 TI - Torsion of a hepatic lobe in the neonate--ultrasound findings. AB - We report a case of projectile vomiting in an infant, secondary to torsion of an accessory lobe of the liver, imaged by ultrasound. PMID- 1508587 TI - Esophageal pseudodiverticulosis: two new cases in children. AB - Esophageal intramural pseudodiverticulosis (EIPD) is an uncommon entity in which distended esophageal mucous glands form flask-like outpouchings from the esophagus. Its relationship with esophagitis, gastroesophageal reflux, and benign stricture suggests that it is a consequence of inflammation. PMID- 1508588 TI - New concepts in preoperative imaging of anorectal malformation. New concepts in imaging of ARM. AB - In this study of 14 patients with anorectal anomalies CT and MRI were employed for preoperative assessment. The use of a pressure enhanced water soluble enema via the colostomy proved to be an extremely efficient method for showing a fistula. MRI studies were enhanced by the use of vaseline oil and in one case this technique was used prior to surgery to provide important information by injecting through a perineal fistula. CT and axial MRI proved to be more valuable than sagittal MRI which is only useful for the length of the atretic segment. The authors consider that a combined approach using pressure enhanced water soluble enema and MRI will provide the most valuable preoperative information to plan a successful operative approach and enable an accurate prognostic evaluation of continence in these difficult and complex patients. PMID- 1508590 TI - Renal cell carcinoma in childhood. AB - The imaging features of renal cell carcinoma in 4 young patients (age 7 to 14 years) are described. A high proportion (75%) showed calcification on plain radiographs or computed tomography (CT). Both patients who underwent CT showed well defined high density tumours which were also echogenic on ultrasound examination. These findings are significantly different to those most commonly seen on studies of the tumour in adults. PMID- 1508589 TI - Three pediatric patients with extension of prostatic embryonal rhabdomyosarcoma anterior to the bladder into the space of Retzius. AB - Invasive embryonal rhabdomyosarcoma of the prostate often extends superiorly into the bladder base requiring partial cystectomy as part of excision of the primary tumor. Three patients were studied with ultrasonography CT and MRI and showed the extension of the tumor superiorly and anterior to the bladder in the prevesical space of Retzius. Complete excision with bladder sparing was successful in two of the patients. The imaging of pelvic tumors in children (although well studied with ultrasonography, CT) is helped by MRI in the sagittal plane and/or lateral films of intravenous pyelograms and cystograms to establish the relation of the tumor to the bladder. PMID- 1508591 TI - Inferior vena cava--right atrial tumor thrombus in malignant pelvic bone tumors in children. AB - Two patients with IVC and right atrial tumor thrombus associated with malignant bone tumors are described. Other tumors such as Wilms', renal cell CA, testicular adrenal and hepatic neoplasms have also been reported to invade the IVC. Ultrasound, CT and MRI are helpful in evaluating the presence of vascular thrombosis as well as its longitudinal extent, and intracardiac involvement. PMID- 1508592 TI - Extramedullary hematopoiesis in the kidneys in infant siblings with myelofibrosis. AB - Extramedullary hematopoiesis (EMH) is known to occur in clinical settings associated with severe anemia. Because very young children with anemia can usually recruit the still large compartment of red marrow, EMH is more frequently seen in adults. We have observed two young girls, who were unable to produce sufficient blood products in their marrow and instead developed EMH, one with documented and rarely reported renal involvement. They are described below. PMID- 1508593 TI - Splenic hemangioma--report of three pediatric cases with pathologic correlation. AB - Splenic hemangioma is a very rare neoplasm in children. We report three cases of splenic hemangioma, two of solitary hemangioma and one of hemangiomatosis. Two patients had hematologic disorders related to hemangioma. Imaging findings of this entity are presented and discussed with emphasis on pathologic correlation. PMID- 1508594 TI - Single system ectopic ureters and ureteroceles associated with dysplastic kidney. AB - Eight children forming an uncommon subgroup of renal obstructive dysplasia are presented. Each child had a nonfunctioning dysplastic kidney with a single collecting system with ectopic ureteral insertion and/or ureterocele. Five of the children had classic multicystic dysplastic kidneys, one had the hydronephrotic type of multicystic dysplastic kidney and two had hypoplastic kidneys. Other significant medical problems in 5 of the 8 children (63%) included VACTERL association, congenital heart disease and other genitourinary malformations. Unlike some children with unilateral multicystic dysplastic kidney, this subgroup of children has an increased risk of infection. They must be correctly identified on imaging so that tailored clinical management decisions can be made and associated anomalies detected. PMID- 1508595 TI - Cranial CT and MRI in malignant phenylketonuria. AB - Malignant phenylketonuria is a rare disease caused by a deficiency in dihydropteridine-reductase which induce a hyperphenylalaninemia and a deficiency of neurotransmitters such as 3,4,dihydroxyphenylalanine (DOPA) and 5 hydroxytryptophan. The case of a patient with malignant phenylketonuria (PKU) who underwent both CT and MR Imaging is reported. CT demonstrated the characteristic calcifications of the basal ganglia. MRI demonstrated areas of hypersignal on T1 images in the basal ganglia, subcortical frontal and occipital white matter and cortex probably corresponding to calcifications. The MR findings are not specific but could be useful in monitoring the diet and neurotransmitter substitution therapy. PMID- 1508596 TI - Asymmetry of salivary gland I123 metaiodobenzylguanidine (MIBG) uptake in a patient with cervical neuroblastoma and Horner's syndrome--possible etiologic mechanisms. AB - Horner's syndrome may be due to a variety of serious underlying disorders including cervical neuroblastoma. Horner's syndrome results from a unilateral disruption of the sympathetic innervation to the head and neck. We report a patient with cervical neuroblastoma in whom post operative metaiodobenzylguanidine (MIBG) scans showed a striking decrease in uptake in the ipsilateral salivary glands. Since the bio-distribution of I123 metaiodobenzylguanidine in the salivary glands in also dependent on sympathetic innervation, the presence of Horner's syndrome can be reflected in the MIBG scan. PMID- 1508597 TI - CT in childhood allergic bronchopulmonary aspergillosis. AB - CT of the thorax done during acute severe asthma in two paediatric patients demonstrated central bronchiectasis, a sine qua non for the diagnosis of allergic bronchopulmonary aspergillosis. Bronchography, regarded as the gold standard, was done subsequently on recovery. A comparative segmental analysis revealed that CT was able to identify immediately 24 of 27 segments which showed central bronchiectasis on bronchography. Early diagnosis with the aid of CT enabled immediate intervention which may have helped to prevent further lung damage in the paediatric patients. PMID- 1508598 TI - Pulmonary nocardiosis manifested as miliary nodules in a neonate--a case report. AB - A case of pulmonary nocardiosis in a 18-day-old neonate is presented. The chest roentgenograms demonstrated the widespread nodularities, mimicking miliary tuberculosis. Nocardiosis is rare in childhood but should be included in the differential diagnosis of the disseminated nodularities seen in the chest roentgenogram. PMID- 1508599 TI - Pedunculated focal nodular hyperplasia. PMID- 1508600 TI - Chest wall deformity and respiratory distress in a 17-year-old patient with achondroplasia: CT and MRI evaluation. AB - A marked thoracic deformity associated with intrathoracic tracheal narrowing was seen in a 17-year-old with achondroplasia and dyspnea. The role of chest deformity and its evaluation by CT and MRI in achondroplastic patients with respiratory symptoms are considered. PMID- 1508601 TI - Candida epiglottitis presenting as stridor in a child with HIV infection. AB - Invasive laryngeal candidiasis is an uncommon cause of epiglottitis, seen most often in immunocompromised or antibiotic-treated patients. We present the clinical and radiographic findings in an HIV-infected infant who developed significant stridor due to candidal epiglottitis. Stridor or hoarseness of unknown cause in an immunocompromised patient should lead to prompt evaluation for opportunistic laryngeal infection. PMID- 1508602 TI - Increased biosynthesis of vasoactive prostanoids in Schonlein-Henoch purpura. AB - Schonlein-Henoch purpura (SHP) is an acute immune-mediated vasculitis characterized by infiltration of polymorphonuclear leukocytes into the vessel wall causing damage to the vascular endothelium by the release of proteolytic enzymes. The local inflammatory and thrombotic process may be regulated by increased biosynthesis of vasoactive prostanoids. We investigated the biosynthesis of thromboxane A2 (TxA2), a potent vasoconstrictor and platelet agonist, prostacyclin (PGI2), a vasodilator and platelet antagonist, and prostaglandin E2, a mediator of inflammation, in 14 children with SHP by physicochemical analysis of index metabolites in plasma and urine. TxA2 and PGI2 biosynthesis in the systemic circulation was significantly elevated in the acute phase of the disease and correlated with the degree of clinical symptoms. Recurrent episodes of the disease were associated with phasic increases of plasma and urinary TxA2 and PGI2 metabolites. Renal TxA2 formation was highest in two patients presenting with the nephrotic syndrome and extracapillary glomerulonephritis. Prostaglandin E2 biosynthesis in the systemic circulation was increased in the acute phase of the disease. The enhanced TxA2 formation is consistent with phasic platelet activation in SHP. The increased PGI2 biosynthesis reflects endothelial cell damage and may be a response of vascular endothelium to modulate platelet-vessel wall and leukocyte-vessel wall interactions. Increased prostaglandin E2 formation, which probably derives from activated polymorphonuclear leukocytes and macrophages, is thought to be related to the inflammatory process in SHP. PMID- 1508604 TI - Alterations in human fetal hematopoiesis are associated with maternal HIV infection. AB - In the majority of adult and pediatric patients with AIDS, hematologic abnormalities including leukopenia, anemia, and thrombocytopenia are commonly observed. In addition to these findings, changes in hematopoietic progenitor cells occur, including a reduction of multipotential-forming units, granulocyte macrophages, macrophage as well as eosinophil colony-forming units, and bone marrow erythroid burst-forming units. This study examined alterations in human fetal liver hematopoiesis in 2nd trimester abortuses from human immunodeficiency virus (HIV)-seropositive women. The differentiation and growth potential of hematopoietic cells in vitro were monitored. Upon initial isolation, some populations of liver hematopoietic cells from abortuses of HIV-seropositive women were significantly decreased when compared to age-matched samples from fetuses of normal females including the percentage of early T cells [cluster of differentiation (CD)2], B cells (CD19), and early monocytes (CD14). A decrease in multipotent progenitors (CD34), myelomonocytes (CD33), and panleukocytes (CD45) was also observed. In contrast, after 21 d in culture, cells from HIV abortuses demonstrated an increase in the percentage of CD14 cells when stimulated with erythropoietin and granulocyte-monocyte colony-stimulating factor, as well as an increase in CD45 phenotype after exposure to granulocyte-monocyte colony stimulating factor alone. These samples showed a persistence of erythropoietic elements (transferrin and CD36 phenotype) when compared to normal controls. No significant difference in the in vitro growth of hematopoietic progenitors (bone marrow erythroid burst-forming units, granulocyte-macrophage colony-forming units, and multipotential forming units) between these samples and normal controls was found.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1508603 TI - Development of intestinal mucosal immunity in fetal life and the first postnatal months. AB - Nine premature infants who were either stillborn or who died shortly after delivery (gestational age, 24-32 wk), eight full-term infants who died during the first 3 postnatal wk, and four infants who died in the postneonatal period were studied by immunohistochemistry for duodenal expression of secretory component (SC) and epithelial HLA class I and II determinants and for the presence of IgA-, IgM-, and IgG-producing immunocytes. Only small amounts of SC appeared before the 29th gestational wk, but thereafter it increased rapidly; 1 wk after birth, SC showed an adult distribution pattern. Epithelial class I was expressed throughout the period investigated, whereas class II (HLA-DR) determinants were absent on the duodenal villi until 1 wk after birth. HLA-DP and -DQ were not expressed by the epithelium. No IgA immunocytes were seen before 1 wk after birth, whereas a few IgM- and IgG-producing cells were present throughout the period studied. The intense epithelial HLA-DR expression from the 2nd postnatal wk, along with SC and the appearance of IgA immunocytes, suggests that the intestinal immune system is modulated in response to environmental factors shortly after birth. PMID- 1508605 TI - A mutation in the E1 alpha subunit of pyruvate dehydrogenase associated with variable expression of pyruvate dehydrogenase complex deficiency. AB - Defects in pyruvate dehydrogenase, the first catalytic component of the pyruvate dehydrogenase complex, are the most common cause of pyruvate dehydrogenase complex deficiency. A family with variable pyruvate dehydrogenase complex deficiency had been described in which cultured skin fibroblasts of affected family members had normal pyruvate dehydrogenase complex activity, but different tissues and blood lymphocytes had significantly diminished activities. Enzymatic activity and immunoblot studies indicated that pyruvate dehydrogenase was affected. Further evidence is presented here showing that the defect affecting pyruvate dehydrogenase complex activity is posttranscriptional. Sequencing of the coding region of the alpha-subunit of pyruvate dehydrogenase revealed a point mutation in the codon for amino acid 234 resulting in a substitution of glycine for arginine. Study of other members of the family suggested that this mutation is inherited in a sex-linked mode. The point mutation is located in a highly conserved region of the pyruvate dehydrogenase alpha-subunit gene that contains both hydrophobic and positively charged amino acid residues. Variable expression of pyruvate dehydrogenase complex deficiency in this case may be due to instability of the pyruvate dehydrogenase heterotetramer in specific tissues because of a disruption in subunit-subunit interaction. PMID- 1508607 TI - Copper status of very low birth weight infants during the first 12 months of infancy. AB - The Cu intake and status of 106 very low birth weight (VLBW) infants (birth weight 1152 +/- 251 g, gestational age 29 +/- 3 wk, mean +/- SD) were determined approximately 1 mo before hospital discharge, at discharge (time 0), and at 3, 6, 9, and 12 mo +/- 3 wk corrected for gestational age. Infants were fed either formula plus supplemental Zn/Cu (SUPPL, n = 29); formula plus placebo (PLAC, n = 26); or a low birth weight formula (LBWF, n = 26) or were breast-fed (BRMLK, n = 25). Plasma Cu levels in the formula-fed infants increased significantly at each time period with no significant differences between feeding groups. Hair Cu was significantly higher in the SUPPL group compared to the PLAC, LBWF, and BRMLK groups at 3 and 6 mo. Erythrocyte Cu,Zn-superoxide dismutase (CuZnSOD) activity was lowest in the PLAC group. Cu intake was positively correlated with both hair Cu (r = 0.291, p less than 0.0001) and erythrocyte CuZnSOD activity (r = 0.281, p less than 0.001) but not with plasma Cu. An increasing number of formula-fed infants had very low CuZnSOD activity (less than 2 SD below mean) with increasing age (n = 1, 2, 8, 11, and 13 infants at times 0, 3, 6, 9, and 12 mo, respectively). At 12 mo, approximately one third of the formula-fed VLBW infants in this study had low Cu status as assessed by CuZnSOD activity. Infants with the lowest CuZnSOD activity were those with the largest weight gains from 0 to 6 mo and were observed in all formula-fed groups.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1508606 TI - Decline of exocrine pancreatic function in cystic fibrosis patients with pancreatic sufficiency. AB - Patients with cystic fibrosis and pancreatic sufficiency were investigated for evidence of progressive pancreatic disease. From a cohort of 630 patients, 20 pancreatic-sufficient patients became pancreatic insufficient after an average duration of 5.6 y (range 0.6-20.6 y) from diagnosis. Among 54 patients documented to be pancreatic sufficient by direct pancreatic stimulation test, 47 remained pancreatic sufficient and seven developed pancreatic insufficiency. The patients who ultimately developed pancreatic insufficiency were younger and had greatly reduced outputs of enzyme, fluid, and electrolytes. Those who remained pancreatic sufficient showed enzyme secretion close to or within the non-cystic fibrosis control range. Twenty of these patients underwent a second pancreatic stimulation test after an average interval of 4 y (range 1.3-6.2 y). No significant alteration in enzyme, fluid, or electrolyte output was seen in the patients who remained pancreatic sufficient, but there was further reduction in enzyme and fluid output in the patients who developed pancreatic failure. In conclusion, the majority of pancreatic-sufficient patients with pancreatic enzyme secretion within the control range showed no deterioration of function over an extended time period. However, a small number of pancreatic-sufficient patients with reduced enzyme and fluid secretion are at risk of pancreatic failure. PMID- 1508608 TI - Selenium and glutathione peroxidase levels in premature infants in a low selenium community (Christchurch, New Zealand). AB - By world standards, the selenium status of the adult population of Christchurch, New Zealand is low. To determine the status of infants undergoing neonatal intensive care, plasma and red cell selenium and glutathione peroxidase levels were measured in infants admitted to the regional neonatal unit. Plasma levels in all newborn infants were one third to one half those in adults. Premature infants had levels significantly lower than those in cord blood from term infants, but their levels were not different from those of term infants admitted to the unit. There were no differences between adult and infant red cell levels. The premature infants remaining in the neonatal unit showed dramatic decreases in plasma selenium and glutathione peroxidase with age, with many infants having selenium levels of less than 0.13 mumol/L (10 micrograms/L). Low levels were seen in infants fed orally as well as those on parenteral nutrition. Thus, the low selenium status of New Zealanders is associated with particularly low selenium levels in premature infants. Because these infants have a high risk for oxidative diseases such as bronchopulmonary dysplasia (chronic lung disease) and retinopathy of prematurity, the possibility that these conditions are more serious in the New Zealand population needs to be assessed and consideration given to dietary supplementation. PMID- 1508609 TI - Transfer and metabolism of retinol by the perfused human placenta. AB - The transfer and metabolism of retinol by human placenta was investigated using an in vitro perfusion system with independent maternal and fetal circulations. 3H retinol bound to albumin added to the maternal perfusate was rapidly taken up and concentrated by the placenta to levels 16.5 +/- 5.28 times the maternal perfusate. Approximately 8% of the retinol retained in the placenta was esterified. No metabolites were detected in the perfusates. Perfusion of placenta with retinol bound to retinol-binding protein (RBP) reduced the placental concentration to 4.4 +/- 1.72 times the maternal concentration and eliminated evidence of metabolism. The transfer rate of RBP:3H-retinol was less than that of albumin:14C-retinol when measured concurrently in three experiments (clearances 0.11 versus 0.75 mL/min, 0.21 versus 1.7 mL/min, and 0.29 versus 0.48 mL/min, respectively). Transfer of the radioactive retinol was more rapid than 125I-RBP or albumin, indicating that retinol was transferred independently of the proteins. The transfer index of retinol (clearance retinol:clearance L-glucose) was 0.73 +/- 0.085 compared to 2.1 +/- 0.36 for thiamin and 3.4 +/- 0.95 for riboflavin, both water-soluble vitamins with active transport systems. The retinol transferred to the fetal perfusate is not bound to RBP, as demonstrated by gel filtration chromatography and chromatography on a transthyretin affinity column, despite the availability of RBP in the cord serum added to the perfusate. The endogenous retinol in the cord serum is bound to RBP.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1508611 TI - The influence of thyroxine on the differentiation of adipose tissue and skin during fetal development. AB - Preobese fetuses have elevated thyroid hormone levels and depressed growth hormone levels relative to lean fetuses. Therefore, we are studying various experimental fetal pig models to explore the relationship between endocrine status and onset of obesity. In the present study, intact and hypophysectomized (d 70) fetuses were implanted with thyroxine (T4) pellets on d 70 of gestation, and blood, adipose tissue, and skin samples were obtained upon removal of d 90 of gestation. Body weights were similar for all groups and T4 treatment reversed myxedema in hypophysectomized fetuses. Serum T4 levels were elevated (p less than 0.05) and skin and hair development were enhanced (p less than 0.05) to a similar degree by T4 treatment in intact and hypophysectomized fetuses. However, T4 did not influence adipose tissue development in intact fetuses, but markedly enhanced development in hypophysectomized fetuses. For instance, fat cell size and lipogenic enzyme activities in hypophysectomized fetuses were increased (p less than 0.05) by 5-mg and 15-mg T4 treatments, with a marked increase (p less than 0.05) in apparent fat cell number with the 15-mg T4 treatment. In contrast, there was no effect of T4 (15 mg) on these parameters in intact fetuses. Therefore, fetal obesity may be directly associated with elevated thyroid hormone levels and suppressed growth hormone levels, but not with elevated T4 levels alone. PMID- 1508610 TI - Binding of placental lactogen and growth hormone to fetal sheep fibroblasts. AB - Growth hormone (GH) regulates growth and development in the postnatal period but lacks somatotropic activity in the fetus. In contrast, the placental hormone placental lactogen (PL) stimulates amino acid transport, DNA synthesis, and somatomedin production in isolated fetal tissues, suggesting that PL may function as a "fetal GH." To elucidate the mechanisms by which PL exerts GH-like effects in fetal tissues, we examined the binding of PL, GH, and prolactin to cultured skin fibroblasts obtained from midgestational fetal lambs. Ovine fetal fibroblasts bound radiolabeled ovine PL (oPL) specifically and with high affinity (EC50 0.20 nM). In competitive displacement assays using 125I-oPL as the radioligand, the potency of unlabeled oPL was eight to 12 times greater than that of ovine GH and congruent to 1000 times greater than that of ovine prolactin. Covalent cross-linking of 125I-oPL (22 kD) to ovine fetal fibroblasts revealed a specific hormone-receptor complex with an apparent M(r) of 130,000, suggesting that the high affinity oPL binding site has a molecular mass of approximately 108 kD. The specific bindings of radiolabeled ovine GH (0.6% per 250 micrograms protein) and ovine prolactin (0.04% per 250 micrograms protein) were only 1/15 and 1/230 that of radiolabeled oPL (9.1% per 250 micrograms protein), and no specific cross-linking of 125I-ovine GH or 125I-ovine prolactin to ovine fetal fibroblasts was detected. These findings demonstrate preferential binding of PL by isolated fetal sheep fibroblasts in culture, providing a cellular mechanism whereby PL may exert growth-promoting effects in the fetus. PMID- 1508612 TI - Effect of prenatal betamethasone/thyrotropin releasing hormone treatment on somatosensory evoked potentials in preterm newborns. AB - The maternal administration of betamethasone and thyrotropin releasing hormone (TRH) to accelerate the maturation of the fetus is an increasingly adopted strategy to prevent neonatal morbidity in preterm infants. The effect of this prenatal treatment on the neural maturation of the infant was assessed by measuring somatosensory evoked potentials (SEP) in preterm infants (gestational age 29-36 wk) on the 1st postnatal day, at the age of 1 wk, and before discharge. The N1 latency values of the SEP obtained in 14 infants who were exposed prenatally to betamethasone/TRH were compared with the N1 latencies measured in 12 control infants. On the 1st postnatal day, the N1 latencies in the betamethasone/TRH-treated infants were strikingly shorter (p less than 0.01) than in the controls. However, at the age of 1 wk and at discharge, the N1 latency values of both groups were similar. In conclusion, the present study provides the first solid evidence for the concept that the prenatal exposure to betamethasone/TRH accelerates the SEP-assessed neural maturation of the human fetus, that this prenatal acceleration is followed by a compensatory relative deceleration during the early neonatal period, and that the subsequent SEP assessed neural maturation proceeds at a normal velocity. PMID- 1508614 TI - Naloxone does not alter the arousal response decrement after repeated exposure to hypoxemia during sleep in lambs. AB - Experiments were done to determine if endogenous opiates cause the arousal response decrement that follows repeated exposure to hypoxemia during sleep in lambs. Five lambs were anesthetized and instrumented for sleep staging and measurement of arterial Hb oxygen saturation. No sooner than 3 d after surgery, measurements were made in quiet sleep and active sleep during control periods when the lambs were breathing 21% oxygen and during experimental periods when the lambs were breathing 5% oxygen. The experimental period was terminated during each epoch by changing the inspired gas mixture back to 21% oxygen, once the lamb aroused from sleep. After each lamb had been exposed to 5% oxygen during 100 consecutive epochs of sleep, naloxone--an opiate antagonist--was given i.v. in a dose of 3 mg/kg as a bolus. The animals continued to be exposed to 5% oxygen during six more epochs of sleep after the administration of naloxone. Arousal occurred from both sleep states during rapidly developing hypoxemia but was delayed in active sleep compared to quiet sleep. The arterial Hb oxygen saturation at arousal was significantly lower, and the time to arousal was significantly longer with repeated exposure to hypoxemia during both quiet sleep and active sleep. Naloxone did not alter this arousal response decrement to hypoxemia. Thus, our data provide evidence that endogenous opiates do not play a major role in causing the arousal response decrement that follows repeated exposure to hypoxemia during sleep in lambs. PMID- 1508613 TI - Prenatal dexamethasone treatment improves survival of newborn rats during prolonged high O2 exposure. AB - Prenatal dexamethasone (DEX) treatment is known to accelerate the maturation of both the surfactant system and the fetal lung antioxidant enzyme (AOE) system (Frank L, Lewis P, Sosenko IRS: Pediatrics 75:569-574, 1985). Because of this stimulatory effect of prenatal DEX on the normal late gestational development of the AOE system, we questioned whether this treatment might have a salutary effect on the ability of the newborn rat to tolerate early and prolonged exposure to hyperoxia, inasmuch as the AOE are the primary lung defensive system against high O2 challenge. In nine experiments with term newborn rats in greater than 95% O2, the composite percentage of survival was significantly greater in the prenatal DEX pups at all time periods in hyperoxia from 7 d [control pups, 67 of 94 (71%); prenatal DEX, 96 of 99 (97%)] to 14 d [controls, 10 of 32 (31%); prenatal DEX, 18 of 33 (55%)] (p less than 0.01). In addition to survival per se, the prenatal DEX pups showed significantly decreased lung wet weight/dry weight ratios, pathologic evidence of pulmonary edema, and lung conjugated dienes versus the O2 control newborn group. Of the many comparative parameters examined, the major difference found between the two groups was in the pulmonary AOE responses to hyperoxia. By 2 d in hyperoxia, the prenatal DEX rat pups showed significantly elevated superoxide dismutase, catalase, and glutathione peroxidase activities compared to air control pups, and at 4 and 7 d in O2 the AOE levels were consistently greater in the DEX group than the AOE responses in the control O2 pups.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1508615 TI - Speed and profile of the arterial peripheral chemoreceptors as measured by ventilatory changes in preterm infants. AB - To measure the response time of the peripheral chemoreceptors, we studied 13 preterm infants [birth weight 1602 +/- 230 g (mean +/- SEM); gestational age 31 +/- 1 wk; postnatal age 15 +/- 1 d] during inhalation of 21% O2 (15 +/- 5 s) followed by 100% O2 (1 min). We used a flow-through system to measure ventilation and gas analyzers to measure alveolar gases. Hypoventilation was observed at 3.6 +/- 0.6 s and was maximal at 6.8 +/- 1 s after O2 began. This maximal response was always associated with an apnea (greater than 3 s). Alveolar PO2 increased from 13.5 +/- 0.1 kPa (101 +/- 0.8 torr) (control) to 28.0 +/- 1.2 kPa (210 +/- 9 torr) (1st O2 breath), to 42.0 +/- 2.4 kPa (315 +/- 18 torr) (1st hypoventilation), to 45.9 +/- 4.1 kPa (344 +/- 31 torr) (breath preceding maximal response), and to 53.6 +/- 4.1 kPa (402 +/- 31 torr) (at maximal response). Minute ventilation was 0.192 +/- 0.011 (control), 0.188 +/- 0.011 (1st O2 breath), 0.088 +/- 0.016 (1st hypoventilation; p less than 0.0001), 0.122 +/- 0.016 (breath preceding maximal response; p less than 0.0002), and 0.044 +/- 0.011 L/min/kg at maximal response (p less than 0.0001). This decrease in ventilation was due to a decrease in frequency with no appreciable change in tidal volume. The initial period of hypoventilation (19 +/- 4 s) was followed by a breathing interval (10 +/- 2 s) and a second period of hypoventilation (14 +/- 3 s) before continuous breathing resumed.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1508616 TI - ATP-sensitive potassium channels in neonatal and adult rabbit ventricular myocytes. AB - The properties of the ATP-sensitive potassium (KATP) current were studied in freshly isolated rabbit ventricular myocytes using the patch clamp technique. Removing ATP from the bath (intracellular) solution activated a large K+ conductance in patches from neonatal cells with properties similar to those of KATP channels in other preparations. In membrane patches from neonatal ventricular myocytes, the density of KATP channels was higher than the density of inwardly rectifying K+ channels and the mean patch KATP current was approximately 10 times that of the inwardly rectifying K+ current, at a patch membrane potential of -60 mV. Glibenclamide (10 microM) in the bath solution decreased the number of functional KATP channels, the open-state probability, and the mean patch membrane current. The single-channel conductance of the KATP channel was dependent on the external K+ concentration, and the relationship between channel conductance and external K+ concentration was fit by an exponential equation. In addition, the voltage dependence, channel density, and open-state probability of this channel were compared between neonatal and adult isolated ventricular myocytes. The single-channel conductance and channel density of the KATP channel in neonatal myocytes were significantly smaller than in adult cells. These results suggest that age-related changes occur in the properties of KATP channels. PMID- 1508617 TI - Acetylcholine-induced coronary vasoconstriction and negative inotropy in the neonatal pig heart. AB - We investigated the influence of exogenously administered acetylcholine, nitric oxide, ADP, ATP, bradykinin, and substance P on coronary vascular tone in isolated, neonatal pig hearts (less than or equal to 4 d). Paced (180 bpm), isovolumically beating hearts underwent retrograde aortic perfusion, with an erythrocyte-enriched solution (hematocrit 0.15-0.20) at constant coronary flow (approximately 2.5 mL/min/g) corresponding to a perfusion pressure of approximately 60 mm Hg. Agonists were injected into the aortic root, and the peak change in coronary perfusion pressure from baseline and left ventricular pressure development were assessed. Nitric oxide (3 microL), ADP (30 nmol), ATP (30 nmol), bradykinin (125 ng), and substance P (50 ng) decreased the perfusion pressure (vasodilation) by 16.9 +/- 1.2, 25.3 +/- 4.4, 18.3 +/- 1.2, 18.9 +/- 1.4, and 7.1 +/- 1.6 mm Hg, respectively. Acetylcholine (0.5 and 1.0 nmol) produced a modest decrease in perfusion pressure (vasodilatation) of 4.2 +/- 0.8 and 3.8 +/- 0.5 mm Hg, respectively, whereas acetylcholine (5, 20, and 100 nmol) increased the perfusion pressure (vasoconstriction) by 16.7 +/- 2.7, 48.2 +/- 8.2, and 85.3 +/- 15.1 mm Hg, respectively. Acetylcholine also decreased left ventricular peak systolic pressure from 108.7 +/- 5.0 to 69.2 +/- 4.6, 56.3 +/- 6.1, and 48.2 +/- 6.4 mm Hg, for the 5, 20, and 100 nmol doses, respectively. Responses to acetylcholine were abolished by atropine (50 nmol). In a separate group of hearts, indomethacin (10(-6) M) reduced the peak change in perfusion pressure for the 5, 20, and 100 nmol doses of acetylcholine by 87%, 66%, and 48%, respectively.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1508618 TI - Random-zero sphygmomanometer, Rose's tape, and the accuracy of the blood pressure measurements in children. AB - In the Cardiovascular Risk in Young Finns project, blood pressure (BP) was measured in 3549 randomly selected children aged 6-18 y in 1980, and 2887 and 2500 of the same individuals in 1983 and 1986, respectively. An ordinary mercury sphygmomanometer (OMS) was used in the first two surveys and a random-zero sphygmomanometer (RZS) in the third survey. Systolic and diastolic BP were lower when measured with an RZS than with an OMS and the shape of the age-related BP curve obtained with an RZS was significantly different from that obtained with an OMS, because low BP values were apparently measured more accurately with the former. Use of the RZS did not affect the distribution of the BP values. Rose's tape readings were used to evaluate the effect of training and to control the accuracy of the BP measurements. According to Rose's tape readings, Korotkoff's 4th phase BP was more difficult to measure accurately than 5th phase (p = 0.002). The mean values for the differences between the correct and actual BP readings on the Rose's tape were -1.2 mm Hg (SD 2.1) for systolic BP, 8.3 mm Hg (SD 13.6) for diastolic Korotkoff's 4th phase BP, and 1.2 mm Hg (SD 7.0) for diastolic Korotkoff's 5th phase BP, with a negative value indicating that the BP phase was measured lower than the correct value. Terminal digit preference was present in each survey to such an extent that it could have hampered the reaching of reliable conclusions from the data obtained with an OMS. The bias caused by terminal digit preference was obviated by the RZS.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1508619 TI - Attention in visual search: multiple search classes. AB - Data from visual-search tasks are typically interpreted to mean that searching for targets defined by feature differences does not require attention and thus can be performed in parallel, whereas searching for other targets requires serial allocation of attention. The question addressed here was whether a parallel serial dichotomy would be obtained if data were collected using a variety of targets representing each of several kinds of defining features. Data analyses included several computations in addition to search rate: (1) target-absent to target-present slope ratios; (2) two separate data transformations to control for errors; (3) minimum reaction time; and (4) slopes of standard deviation as a function of set size. Some targets showed strongly parallel or strongly serial search, but there was evidence for several intermediate search classes. Sometimes, for a given target-distractor pair, the results depended strongly on which character was the target and which was the distractor. Implications from theories of visual search are discussed. PMID- 1508620 TI - Auditory apparent motion in the free field: the effects of stimulus duration and separation. AB - The effects of stimulus duration and spatial separation on the illusion of apparent motion in the auditory modality were examined. Two narrow-band noise sources (40 dB, A-weighted) were presented through speakers separated in space by 2.5 degrees, 5 degrees, or 10 degrees, centered about the subject's midline. The duration of each stimulus was 5, 10, or 50 msec. On each trial, the sound pair was temporally separated by 1 of 10 interstimulus onset intervals (ISOIs): 0, 2, 4, 6, 8, 10, 15, 20, 50, or 70 msec. Five subjects were tested in nine trial block; each block represented a particular spatial-separation-duration combination. Within a trial block, each ISOI was presented 30 times each, in random order. Subjects were instructed to listen to the stimulus sequence and classify their perception of the sound into one of five categories: single sound, simultaneous sounds, continuous motion, broken motion, or successive sounds. Each subject was also required to identify the location of the first-occurring stimulus (left or right). The percentage of continuous-motion responses was significantly affected by the ISOI [F(9,36) = 5.67, p less than .001], the duration x ISOI interaction [F(18,72) = 3.54, p less than .0001], and the separation x duration x ISOI interaction [F(36,144) = 1.51, p less than .05]. The results indicate that a minimum duration is required for the perception of auditory apparent motion. Little or no motion was reported at durations of 10 msec or less. At a duration of 50 msec, motion was reported most often for ISOIs of 20-50 msec.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1508621 TI - Adaptation to auditory motion in the horizontal plane: effect of prior exposure to motion on motion detectability. AB - Thresholds for auditory motion detectability were measured in a darkened anechoic chamber while subjects were adapted to horizontally moving sound sources of various velocities. All stimuli were 500-Hz lowpass noises presented at a level of 55 dBA. The threshold measure employed was the minimum audible movement angle (MAMA)--that is, the minimum angle a horizontally moving sound must traverse to be just discriminable from a stationary sound. In an adaptive, two-interval forced-choice procedure, trials occurred every 2-5 sec (Experiment 1) or every 10 12 sec (Experiment 2). Intertrial time was "filled" with exposure to the adaptor- a stimulus that repeatedly traversed the subject's front hemifield at ear level (distance: 1.7 m) at a constant velocity (-150 degrees/sec to +150 degrees/sec) during a run. Average MAMAs in the control condition, in which the adaptor was stationary (0 degrees/sec,) were 2.4 degrees (Experiment 1) and 3.0 degrees (Experiment 2). Three out of 4 subjects in each experiment showed significantly elevated MAMAs (by up to 60%), with some adaptors relative to the control condition. However, there were large intersubject differences in the shape of the MAMA versus adaptor velocity functions. This loss of sensitivity to motion that most subjects show after exposure to moving signals is probably one component underlying the auditory motion aftereffect (Grantham, 1989), in which judgments of the direction of moving sounds are biased in the direction opposite to that of a previously presented adaptor. PMID- 1508622 TI - The role of symmetry in determining perceived centers within shapes. AB - This study was designed to assess the effects of symmetry and plane of presentation on the determination of the perceptual center of flat figures. Experiment 1 demonstrates the existence of effects in improving center determination, both in the number of sides of the shape and in rotational and reflective symmetry (confounded in the experiment). Experiment 2 shows that the presentation plane has no effect on center determination. In Experiment 3, we divide the effects of the two symmetry types, showing that rotational symmetry alone is as effective as the presence of both symmetry types--that is, the presence of symmetry axes is not very useful in finding perceived centers. PMID- 1508623 TI - Orientation-contingent color aftereffects mediated by subjective transparent structures. AB - We examined whether the orientation-contingent color aftereffect (the McCollough effect) could be mediated by subjective horizontal and vertical structure induced by the perception of transparency. In our experiments, red vertical bars and green horizontal bars were alternated as an adapting stimulus. After adaptation, subjects (n = 6) were asked to adjust the green and red saturation of a test pattern until they obtained a neutral gray. Horizontal and vertical stripes were combined in the test pattern in three different ways: (1) overlapping with a luminance combination that gave rise to a perception of transparent overlays of horizontal and vertical stripes (valid transparency condition), (2) overlapping with luminance combinations that did not induce a perception of transparency (invalid transparency condition) and that appeared more as a patchwork of checks, and (3) presented in adjacent, nonoverlapping areas. Our results showed that the McCollough effect was significantly greater in the valid transparency condition than in the invalid transparency conditions. The effect in the valid transparency condition was nevertheless less strong than was the effect seen with the standard test stimulus made up of nonoverlapping vertical and horizontal stripes. Our results suggest that the McCollough effect can be mediated by the subjective spatial organization (inner representation of vertical and horizontal stripes) that accompanies the perception of transparency in our stimulus. PMID- 1508624 TI - Saccades to targets in three-dimensional space: dependence of saccadic latency on target location. AB - The latency of saccadic movements to targets appearing at various positions in three-dimensional visual space was measured in four experiments. The first experiment confirmed that latencies of saccades to visual targets are greater in the lower visual field and showed that the increase is not influenced by the vertical starting position of the eye in the orbit, nor by a time gap between the fixation offset and the target onset. A hypothesis that this visual field difference was caused by a link between downward saccades and convergence movements was tested by recording saccade latencies when the targets were in a different depth plane from that of the original fixation. We did not find any direct support for the vergence involvement hypothesis, although the lower/upper visual field effect was shown to decrease consistently in monocular viewing. It was also shown that saccades to targets positioned in a different depth plane have longer latencies. In a final experiment, the visual field effect was shown to depend on the egocentric rather than the gravitational vertical. PMID- 1508625 TI - Allocation of visual attention in younger and older adults. AB - Younger and older adults were compared in three experiments, using procedures that had been shown to affect the spread of visual attention. The attentional effects found in previous experiments were replicated. A broader focus of attention speeded responses to peripheral targets. In addition, two established findings concerning aging were replicated: Responses were slower in older than in younger adults, and, in certain conditions, they slowed more rapidly as target eccentricity increased. No interactions of age effects with attentional manipulations were found. The results of all three experiments were consistent with the interpretation that younger and older adults do not differ in the allocation of attention. PMID- 1508626 TI - Suppression of optokinesis by a stabilized target: effects of instruction and stimulus frequency. AB - Subjects viewed a foveally stabilized target presented against a background field of dots moving sinusoidally. Several different modes of viewing the target were used (subjects were instructed to gaze, look, or hold), and the frequency of sinusoidal field motion was varied from 1/32 to 2 Hz. In line with previous findings, the presence of a stabilized target resulted in substantial suppression of optokinesis. The characteristics of this suppression (gain and phase of slow residual eye movements) were dependent on both the mode of viewing the target and the frequency of field motion. When subjects used an imaginary target, little suppression occurred. These findings provide an overall profile of dynamic characteristics of mechanisms involved in the suppression of optokinesis. They support the view that this suppression is significantly determined by the presence of a target against a moving background (even without retinal slip), and by the mode of attending to the target. PMID- 1508627 TI - The effects of complexity on the perception of vibrotactile patterns presented to separate fingers. AB - Pairs of vibrotactile patterns were presented to subjects' left middle and index fingerpads (unilateral presentation) or left and right index fingerpads (bilateral presentation), using two Optacon arrays. A set of simple (one-line) patterns and a set of complex (two-line) patterns were constructed so that they were equally identifiable when presented individually. In Experiment 1, discrimination performance was lower for two-line patterns than it was for one line patterns, and it was lower for unilateral presentation than it was for bilateral presentation. Communality, the number of lines that two patterns share in common, was a major factor in reducing discrimination performance for two-line patterns. Subjects' abilities to identify one member of the pair of patterns were measured in Experiment 2. There were no significant differences in performance between pattern sets or type of presentation when subjects attended to a single pattern. However, when subjects were required to attend to both patterns, identification performance was lower for two-line patterns than it was for one line patterns, and it was lower for unilateral presentation than it was for bilateral presentation. The results suggest that there are limited attentional resources for processing vibrotactile patterns and that more resources are available bilaterally than are available unilaterally. PMID- 1508628 TI - Spatial attention in Ponzo-like patterns. AB - A variant of Ponzo's pattern was devised by drawing converging oblique lines at the ends of each of two horizontal lines that were located directly one above the other. Pairs of converging or diverging fins (either between or outside the horizontal shafts) were systematically removed. The results showed that, as predicted by integrative field theory, oblique lines between the shafts produced more distortion than did oblique lines outside the shafts. Also, it was shown that the attentive field construct in integrative field theory was crucial for predicting patterns of means and variances in this experiment. The modified Ponzo effect was shown to have much in common with the classical Muller-Lyer illusion. The subtle differences between the two were explained by proposing that the size of the optimum attentive field was larger in the Ponzo tasks than in the Muller Lyer tasks because expansion fins are found on both shafts in the Ponzo-like figure. PMID- 1508630 TI - [Growth rate of abdominal aortic aneurysms as measured by Computerized tomography]. AB - To evaluate the growth rate of abdominal aortic aneurysms, sequential computed tomography (CT) examinations were performed on 125 nonoperated patients (M/F 101/24, mean age 67 +/- 8 years, 129 lesions) at intervals of at least 6 months. Growth rates of aneurysms were obtained by subtracting the first from the last diameter and adjusting for examination interval. Mean growth rate was 0.28 +/- 0.26 cm/year. Aneurysms with an initial diameter exceeding 4 or 5 cm showed significantly faster growth than smaller aneurysms. There was no significant correlation between growth rate and atherosclerogenic factors, but systolic blood pressure was significantly higher in patients whose aneurysms ruptured. Our study showed quantitatively that aneurysms with a large diameter have a rapid growth rate, the growth rate of infrarenal aneurysms is significantly faster than that of suprarenal aneurysms, and blood pressure control is important to prevent rupture. PMID- 1508629 TI - Apparent duration and spatial structure. AB - In three experiments, we investigated the relative perceived duration of a full bandwidth image and a set of high- and lowpass filtered images of a scene, briefly presented on a visual display unit. In Experiment 1, the various images were compared with each other, using a paired comparison method. All images were presented for 40 msec, and observers were asked to judge which of each pair of images had the longest duration. The results showed that images containing a wide spatial frequency bandwidth were judged to be of longer duration than were images of a narrower bandwidth, regardless of whether the latter were high- or lowpass filtered. In Experiment 2, a 40-msec presentation of each of the images was compared with a presentation of a probe that was 20, 40, 60, or 80 msec in duration. Observers again judged which of each pair of images had the longest duration. The results were very similar to those of Experiment 1, with wide bandwidth images being judged to be of longer duration than were narrow bandwidth images. In Experiment 3, instead of comparing the various filtered versions of the image with each other, we attempted to obtain a direct measure of perceived duration by comparing a flashing LED to a 40-msec flash of a subset of the images used in the previous experiments. The observers' task was to adjust the duration of the LED flash to match the perceived duration of each image.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1508631 TI - [Clinical evaluation of stent placement for tracheal and bronchial stenosis]. AB - Expandable metallic stents were successfully introduced in 7 patients, including 4 with left main bronchial stenosis caused by bronchopulmonary tuberculosis, 2 with main bronchial stenosis caused by lung cancer and one with tracheal stenosis caused by adenoid cystic carcinoma. The length of stenosis was 1.5-5 cm. The stents were 1.5-2.5 cm long with barbs, and their full expanded diameter was 1.5 cm. Balloon dilatation was performed before stenting in all cases. The stents were inserted by using a 10-12 Fr catheter. In all patients except the one with tracheal stenosis, stents were introduced under local anesthesia without any difficulties. No migration of stents occurred. After stent placement, there were no respiratory difficulties, and radionuclide lung perfusion scan and chest radiographic findings such as lung atelectasis showed marked improvement in three cases. Combined therapy of stent placement and bronchial arterial infusion chemotherapy showed marked effectiveness in one case with lung cancer. Expandable metallic stents were very useful in eliminating tracheobronchial stenosis symptoms. PMID- 1508632 TI - [Magnetic resonance (MR) imaging of chordoma and chondroma in the skull base- differential diagnosis by IR sequence]. AB - Differential diagnosis of chordoma and chondroma in the skull base is sometimes difficult. We retrospectively reviewed the MR images of 14 patients with skull base tumors (nine chordomas, four chondromas and one chondrosarcoma). MR imaging was performed with a 0.5 Tesla system (Picker International). Inversion recovery (IR) (2500-2100/600-500/40), T1-weighted spin echo (SE) (800-600/40), and T2 weighted SE (2500-1800/120) images were obtained. On IR images, seven of eight chordomas showed heterogeneous low signal intensity, and one chordoma and all chondromas showed markedly low signal intensity similar to that of CSF. Calcified or ossified portions of the chondromas were demonstrated as areas of moderately low intensity on IR images. Chondrosarcoma showed moderately low intensity similar to that of chordoma. T1-weighted SE images of chordoma and chondroma showed no difference in signal intensity. On T2-weighed SE images, six of nine chordomas and all chondromas showed markedly high signal intensity. Three chordomas and one chondrosarcoma showed moderately high signal intensity. In the diagnosis of skull base tumors, the IR sequence seems to be useful for differentiating chondroma from chordoma. PMID- 1508633 TI - [Angiographic features of alveolar soft-part sarcoma]. AB - The angiographic findings were analyzed in five patients with alveolar soft-part sarcoma. The angiographic appearance of the tumors was the same in all five cases: hypervascularity of the tumor including encasement, dilatation, tortuosity and displacement of feeding arteries, remarkable tumor stain and early venous filling. These angiographic findings are considered to be characteristic of alveolar soft-part sarcoma in the differential diagnosis of hypervascular soft tissue mass. PMID- 1508634 TI - [Computerized tomography in pulmonary infarction]. AB - We performed a retrospective study of CT findings in 14 patients with 61 lesions of pulmonary infarction diagnosed clinically and radiographically. All cases except one had multiple pleural-based parenchymal lesions, and in five cases the lesions were bilateral. The site of pulmonary infarction was the right lower lobe in 24 lesions, left lower lobe in 19 lesions, right upper lobe and left upper lobe in seven lesions each, and right middle lobe in four lesions. Fifty-nine infarctions (excluding two segmental lesions) were divided into two groups according to the size of the lesions: a group of lesions 2 cm or more in size and a group less than 2 cm. Nineteen lesions in eight patients were in the larger group and 40 lesions in 12 patients in the smaller group. The typical CT findings of larger infarctions were pleural based parenchymal density with truncated apex, centrally directed linear shadow and inside low attenuation area indicating viable lung. Pleural thickening and effusion were frequently seen. No air bronchograms were seen in these subsegmental lesions. Smaller lesions were believed to indicate infarction of a single secondary pulmonary lobule, considering their size and shape. CT scan was able to detect these small lesions (single lobular infarctions) more frequently than chest radiography. One segmental lesion with air bronchogram was thought to represent atelectasis and the other one to represent pulmonary hemorrhage and edema. CT examination is useful for the detection and diagnosis of pulmonary infarction. PMID- 1508635 TI - [An experimental and clinical study of zonography of the lung by means of Fuji computed radiography]. AB - Tomography was conducted for a basic study using a model of the bronchi, pulmonary arteries and veins. When the exposure angle of a tube was changed to 5, 10, 25, and 50 degrees, the width of tomograms became about 10, 4, 2, and 1 cm. When tomograms of exposure angles of 50 degrees and 10 degrees were compared, the former showed fragmentary bronchi, pulmonary arteries and veins, and the latter showed bronchi, pulmonary arteries and veins branching up, down and laterally on one image in one unit and over a wide area. Similar results were obtained in 10 cases of normal volunteer. When 25 cases of lung cancer at the hilum were studied clinically with respect to bronchial lesions, the tomograms with an exposure angle of 10 degrees could point out more lesions than the tomograms with an exposure angle of 50 degrees. In 13 cases (40 lesions) which were compared with the findings of bronchoscopy, the accuracy was only 25% in tomograms with an exposure angle of 50 degrees, and 65% in tomograms with an exposure angle of 10 degrees. These results indicate that tomograms with an exposure angle of 10 degrees are useful for analysis of the bronchi, pulmonary arteries and veins at the hilum of the lung. PMID- 1508636 TI - [Biliary endoprosthesis of malignant biliary obstruction using expandable metallic stent--preliminary clinical evaluation]. AB - Thirty-eight patients with malignant biliary obstruction were treated with expandable metallic stent (EMS). Successful insertion of stents was attained in all cases, and in 34 of 38 patients, the stents remained patent and sufficiently expanded, and led to the removal of external drainage catheter. No serious complications occurred. In two cases, stents were deformed in shape, associated with no side effects. In follow-up, eleven patients developed recurrent jaundice due to tumor ingrowth between the wires and the tumor grew up along the initially placed stents. In six patients, additional stents were installed inside the initially placed stents, in whom the additional stents were placed successfully and remained patent thereafter. The expandable metallic stents were superior to the conventional tube stents, but there were some problems in our limited experience: stents deformity, slipping migration, fracture of stents and rapid obstruction. Further investigation is under way to resolve these problems. Long term trials are required before established routine use of EMS. The expandable metallic stent was, however, expected to offer a new alternative in the management of malignant biliary obstructions and to afford long-term patency of affected biliary tracts. PMID- 1508638 TI - [Single photon emission computed tomography by using fan beam collimator]. AB - A multislice fan beam collimator which has parallel collimation along the cephalic-caudal axis of a patient and converging collimation within planes that are perpendicular to that axis was designed for a SPECT system with a rotating scintillation camera, and it was constructed by the lead casting method which was developed in recent years. A reconstruction algorithm for fan beam SPECT was formed originally by combining the reconstruction algorithm of the parallel beam SPECT with that of the fan beam X-ray CT. The algorithm for fan beam SPECT was confirmed by means of computer simulation and a head phantom filled with diluted radionuclide. Not only 99mTc but also 131I was used as a radionuclide. A SPECT image with the fan beam collimator was compared with that of a parallel hole, low energy, high resolution collimator which was routinely used for clinical and research SPECT studies. Both system resolution and sensitivity of the fan beam collimator were approximately 20% better than those of the parallel hole collimator. Comparing SPECT images obtained from fan beam collimator with those of parallel hole collimator, the SPECT images using fan beam collimator had far better resolution. A fan beam collimator is a useful implement for the SPECT study. PMID- 1508637 TI - [Temperature distribution and geometry of the electrodes in RF interstitial hyperthermia using circular and interstitial electrodes]. AB - To evaluate the feasibility of clinical application of a newly developed interstitial hyperthermia system, which consists of an 8 MHz radiofrequency generator, interstitial needle electrodes, and a superficial circular electrode, we conducted preclinical experiments using an agar phantom and VX-2 carcinoma in the rabbit. In the experiment with an agar phantom, four 4 cm needle electrodes were placed in a square array at intervals of 1.0, 1.5, and 2.0 cm. Thermography demonstrated homogeneous temperature distribution at electrode intervals of 1.0 and 1.5 cm, but hot spots around the electrodes at an interval of 2.0 cm. When electrode deviation was less than 8 degrees from the parallel plane, no temperature deviation was observed. Using two 2 cm electrodes and two 4 cm electrodes in square array, thermography demonstrated a homogeneous temperature distribution in the area surrounded by the electrodes. Even if the electrodes were located at the periphery of the agar phantom, a homogeneous temperature distribution was obtained in the area surrounded by the electrodes. Using four 4 cm electrodes at intervals of 1.5 cm in VX-2 carcinoma in the rabbit, ideal heating was obtained: 42 degrees C at the periphery of the tumor and 43 degrees C at the center. These data suggest that the newly developed interstitial hyperthermia apparatus provides homogeneous heat distribution at electrode intervals of 1.5 cm or less and can be used in a Phase I study for deep-seated or superficial tumors. PMID- 1508639 TI - [Evaluation of thermal damage after hyperthermia on murine experimental tumor by 31P-NMR spectroscopy--correlation between ATP and growth curve]. AB - The possibility of using 31P-NMR spectroscopy (31P-MRS) to estimate the effect of hyperthermic treatment on mouse FM3A tumor was investigated. 1 x 10(6) cells, suspended in saline, were subcutaneously inoculated to the right thigh of C3H mice. For hyperthermic treatment, the tumor-bearing leg was heated by immersing it in a water bath at 44 degrees C for 10, 20 or 30 min. The signal intensities of ATP and Pi of the tumor were measured utilizing the 31P-MRS technique to calculate the ATP/Pi ratio. Immediately after heating, the ATP/Pi ratio decreased markedly. Eighteen hours after hyperthermic treatment, the ratio recovered but was still smaller than the control value, then became almost constant by 24 hours after heating. The ATP/Pi ratio at 24 hours after heating decreased with increased length of heating and was inversely related to tumor regrowth after hyperthermic treatment. We concluded that non-invasive monitoring with 31P-MRS might provide a good indication of the effect of hyperthermic treatment. PMID- 1508640 TI - [New puncture technique for TIPSS (transjugular intrahepatic portosystemic stent shunt)]. AB - To establish a safer puncture method for TIPSS (Transjugular Intrahepatic Portosystemic Stent Shunt), we developed a new percutaneous puncture technique to penetrate portal and hepatic vein trans-hepatically under ultrasonography (US technique). Experimentally we compared this technique with conventional transjugular technique puncturing portal vein through hepatic vein using Ross needle (Ross Needle technique). Success rate is 100% in US technique and 50% in Ross needle technique. Seven complication including intraperitoneal bleeding occurred in Ross needle technique, but no complication in US technique. Conclusively, US technique is a safer and more reliable method than that using Ross needle in the puncture method for TIPSS. PMID- 1508641 TI - [Biliary enhanced MR imaging by Gd-DTPA]. AB - Biliary enhanced MRI (BEMRI) by Gd-DTPA via PTCD and/or PTGBD tube for obstructive jaundice was performed in 8 patients. In all cases, biliary tract was clearly visualised as high signal intensity on T1 weighted images. On same images, primary lesion such as common bile duct cancer was also visualised as well as portal system. In addition, MR angiography (MRA) by 2D-time of flight method was performed. MRA with BEMRI shows portal encasement on the same image as biliary tract obstruction. It suggests MRA with BEMRI may replace the other modality for obstructive jaundice. PMID- 1508642 TI - [Experimental study on the usefulness of the autoperfusion balloon catheter in maintaining the blood supply to the distal organs]. AB - Autoperfusion Balloon Catheters (APBC) were inserted into the renal arteries of seven dogs for about two and a half hours. Abdominal aortography showed renal arterial flow of the kidney obstructed by APBC. Macroscopic and microscopic examination revealed no significant changes in the resected specimen. It is concluded that APBC is useful in cases of proximal arterial occlusion by maintaining the blood supply to the distal organs for relatively short periods and that it can be used for the treatment of rupture of arteries which feed critical organs. PMID- 1508643 TI - [Radiosensitizing effect of a 2-nitroimidazole hydroxamate (KIN-804) to murine tumors]. AB - We studied the toxicity, pharmacokinesis and radiosensitizing effect of a newly developed 2-nitroimidazole-1-methylacetohydroxamate (KIN-804) in C3H/He mice bearing SCC-VII tumor. They were compared with misonidazole. LD50/7 of KIN-804 and misonidazole were 3200 and 2000 mg/kg. The concentration of KIN-804 in the brain and sciatic nerve was at a very low level and its clearance from the sciatic nerve was rapid. Enhancement ratios calculated using the growth delay method were 1.50 for KIN-804 and 1.36 for misonidazole respectively when they were administered by intraperitoneal injection with a dose of 100 mg/kg. KIN-804 was considered to be a promising radiosensitizer because it obtained less toxicity and a higher radiosensitizing activity than misonidazole. PMID- 1508644 TI - [Effect of growth rate of monolayer cells on survival after fractionated irradiation]. AB - This study was performed to determine the effect of the growth rate of monolayer cells on survival following fractionated irradiation. HeLa and RMUG cells that had different radiosensitivities and growth rates (Do value: 2.3 vs 1.5 Gy, doubling time: 17 vs 46 hours) were irradiated with 2 Gy every day. The fractions surviving after fractionated irradiation were compared with those given single doses. The dose modifying factor for fractionated irradiation was larger in RMUG than HeLa: 1.7 and 1.2, respectively. Two clones from ADGU cells that had the same radiosensitivity but different growth rates were also given fractionated irradiation, but there was no difference in surviving fractions. When recovery following two split doses was determined in each type of cell, the results of the fractions surviving after fractionated irradiation were correlated only with recovery between split doses. These suggest that the growth rates of monolayer cells may not modify the fractions surviving after fractionated irradiation, and the monolayer cell system is not suitable for determining the effect of growth rates on survival following fractionated irradiation. PMID- 1508645 TI - [Analysis on combined effect of X-rays with 5-FU on rat subcutaneous gliomas]. AB - In a series of experiments on the combined use of radio- and chemotherapy for malignant glioma, X-rays combined with ACNU or 5-FU treatment caused a supra additive effect on multicellular spheroids in vitro. In the present experiment, the effect of X-rays combined with 5-FU treatment on subcutaneously transplanted rat gliomas of RGC-6 cells was analyzed. The dose-survival curve for X-rays given to tumors in air-breathing rats was biphasic with a terminal slope (D0 = 4.3 Gy) that was parallel to that for tumors in previously killed rats. The hypoxic cell fraction thus obtained from the ratio of the surviving fraction in two parallel curves at 20 Gy was about 7% in the subcutaneous tumors in air-breathing rats. X ray-induced, potentially lethal cellular damage recovered within 8 hours in these tumors. The surviving fraction of cells in the tumors decreased to a minimum at 4 6 hours after a 5-FU injection, but increased thereafter. A biphasic dose response curve for 5-FU was also obtained for cells in these tumors, indicating the presence of 5-FU resistant cells. The effect of X-irradiation given at about 8 hours after a 5-FU injection was greater than the additive effect of both agents acting independently. This was true when an X-ray dose of more than 5 Gy was given. PMID- 1508646 TI - [Evaluation of US contrast medium (LEVOVIST) to experimental liver cancer]. AB - Enhancement of liver cancer on ultrasonography (US) by injection of new contrast medium (LEVOVIST) was performed in rats with 3'-methyl-4-dimethylaminoazobenzene induced hepatic carcinoma. Echosignals of cancer nodules increased remarkably after the intrahepatic arterial injection of LEVOVIST (200, 300 mg/ml), and contrast enhancement was observed for at least 15 minutes. Furthermore, US after the intrahepatic arterial injection of LEVOVIST (200 mg/ml) can visualize small nodule, which was not recognizable on plain US. As a result of increased echosignals of normal liver parenchyma after the intra-portal injection of LEVOVIST (300 mg/ml), the cancer nodules were demonstrated as hypoechoic. These results indicate that this new contrast medium for sonography is effective in the diagnosis of liver cancer. PMID- 1508647 TI - [Gd-DTPA-enhanced MR imaging of the normal facial nerve]. AB - We performed a prospective imaging study of the normal facial nerve within the temporal bone before and after injection of Gd-DTPA. The study included 29 patients using a 1.5T superconducting unit and 40 nerves (right: 21; left: 19) were available for analysis. There was no enhancement of the facial nerve within the internal auditory canal in the entire series. However, the enhancement at the labyrinthine segment was observed in one nerve (3%); at the geniculate ganglion in seven (18%); at the tympanic segment in 18 (45%) and at the mastoid segment in 28 nerves (70%). Our results indicate that enhancement of the facial nerve in normal subjects is not a rare condition. PMID- 1508648 TI - [The study of ultrasonographic diagnosis on breast diseases]. AB - 15 sonomammographic findings of 341 histologically proved breast masses were reviewed to improve and objectify the current diagnostic criteria of sonomammography. The author proposed the renewed plan of the diagnostic criteria and the judgement method of benign or malignant breast masses on an electronic linear scanner, offering the author's original diagnostic concept particularly about the shape and the internal echo. This diagnostic approach demonstrated a sensitivity of 93.2%, specificity of 85.9%, and accuracy of 89.7%, which sufficiently showed to raise differential diagnostic capability for breast masses. PMID- 1508649 TI - [Raise up 99mTc-HMPAO brain SPECT for detecting the changes in cerebral perfusion pressure]. AB - 99mTc-HMPAO crossed the blood brain barrier instantly in proportional to cerebral blood flow. Raise up stress and supine resting 99mTc-HMPAO with brain SPECT was devised for detecting abnormal response in the changes of cerebral perfusion pressure. Asymmetric ratio in the middle cerebral artery area in patients with internal carotid artery occlusion (n = 5) was changed significantly from 0.82 +/- 0.06 to 0.90 +/- 0.06 and that of normal (n = 5) was not changed from 0.94 +/- 0.03 to 0.95 +/- 0.01. Raise up 99mTc-HMPAO brain SPECT enhanced the detectability in abnormality of regional cerebral blood flow and visualized the dys-autoregulated area during blood pressure falls. PMID- 1508650 TI - [Development of a gel phantom for dose distributions by MR imager]. AB - We reported a method of determining spatial dose distributions in tissue equivalent phantoms using nuclear magnetic resonance imaging. To make a gel phantom, a cross-linked dextran gel (Sephadex G-200) was used as fixation agent of a ferrous sulphate solution. Although high quality images are obtained, the cost is very expensive to make the gel. We developed a new gel which is combined with an extra water absorbent polymer (Sumikagel N-100) and Sephadex G-200. The gel permits the determination of dose distributions for three dimensional treatment planning. PMID- 1508651 TI - [Evaluation of aortic distensibility using cine MR imaging]. AB - Regional aortic distensibility was measured noninvasively using cine MR imaging to determine whether it correlates with aging or risk of coronary artery disease (CAD). Twenty-two patients with CAD confirmed by angiography and 33 without CAD underwent cine MR imaging. Thirty-two sequential images were obtained in one cardiac cycle. The cross sectional area of the descending thoracic aorta was measured on both diastolic (A) and systolic (A') images. Aortic distensibility (A.D.) was calculated from the following equation: A.D. = (A'-A)/A/delta P. (delta P represents pulse pressure). Results of a simple regression analysis showed that decreased regional aortic distensibility was significantly correlated with the age of the patients (r = -0.762, p less than 0.005). In addition, the parameter was lower in patients with CAD than those without CAD (p less than 0.05). In conclusion, regional aortic distensibility derived from cine MR imaging is a useful parameter to evaluate not only aging but also pathological atherosclerosis of the aorta. In addition, this parameter might have some potential to evaluate the prediction of CAD in patients with normal serum cholesterol. PMID- 1508652 TI - [Complications of arterial infusion of CDDP in the treatment of malignant neoplasms]. AB - Arterial infusion of cis-diamminedichloroplatinum (CDDP) is an effective therapy for malignant neoplasms. Severe complications after this therapy in 298 patients with malignant tumors were reviewed in our institute from March 1982 to August 1989. Arteries infused with CDDP and the number of infusions were as follows: bronchial artery (a.) 277, hepatic a. 153, internal iliac a. 51, femoral or popliteal a. 15, lumbar a. 6, pulmonary a. 5, esophageal a. 3 and intercostal a. 3. Eight cases of severe complications were encountered: 3 of esophageal ulcer, 3 of spinal paralysis, and one each of mediastinitis and toe necrosis. The arteries responsible for complications were the bronchial a. in 3 cases of esophageal ulcer and 2 of spinal paralysis, intercostal a. in one of spinal paralysis, esophageal a. in one of mediastinitis and popliteal a. in toe necrosis. Complication rates were 2.7% (8/298 cases) and 1.5% (8/518 infusions). Angiotensin II was infused in 6 of 8 of the cases with complications. The complication rate was 2.9% (6/209 infusions) in the group with CDDP and angiotensin II and 0.6% (2/309 infusions) in the group with CDDP only. Arterial infusion of CDDP, especially combined with angiotensin II, should be done in consideration of the arteries responsible for such complications. PMID- 1508653 TI - [Phosphorus 31-magnetic resonance spectroscopic studies of animal liver after extracorporeal shock wave lithotripsy]. AB - The technique of magnetic resonance spectroscopy has been developed, and the study of high-energy phosphate metabolites in the liver using phosphorus 31 magnetic resonance spectroscopy (31P-MRS) has been reported in humans and animals, but few studies have used 31P-MRS for the evaluation of extracorporeal shock wave lithotripsy (ESWL) of the liver. In this study, 31P-MRS was used to evaluate the metabolic changes in hamster liver after ESWL and histological correlation was performed. Syrian golden hamsters were anesthetized and shock waves were irradiated to the left side of the liver. Hamsters were irradiated by LITHOSTAR-PLUS (SIEMENS) at a voltage of 19 KV. 31P-MRS was studied by JNM-GSX model 270 (6.34 Tesla). Typical peaks of 31P-spectra of hamster liver showed a tendency for PDE/beta-ATP, alpha-ATP/beta-ATP and gamma-ATP/beta-ATP to decrease among the irradiated group compared with the control group. However, there were no significant differences in PME/Pi, beta-ATP/Pi or (alpha-ATP-beta-ATP)/beta ATP between the control group and irradiated group. With regard to intracellular pH and PDE/beta-ATP, a decreasing tendency was noted in the irradiated groups (p less than 0.05). There was no difference in the signal intensity of T1WI and T2WI on 1H-MRI, between these two groups. Pathologically, the irradiated group showed minor hemorrhage and edema in the liver, and subcapsular hematoma. The results obtained from 31P-MRS clearly showed the metabolic changes and were correlated well with the histological findings, but MRI was not capable of providing close visualization of post-ESWL liver damage.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1508654 TI - [Transcatheter embolization for huge pulmonary arteriovenous fistula using metallic "spider" and spring embolus--application of hand-made metallic "spider" using partial monorail technique]. AB - We performed transcatheter embolization in two cases with huge pulmonary arteriovenous fistula (AVF) using a metallic "spider" and spring embolus. Conventional spring embolus or detachable balloon could not be used in these cases. Metallic spider was indicated for pulmonary AVF with a feeding artery diameter of more than 16 mm to prevent embolus passing through the AVF. In the first case, we used large handmade metallic spiders of 25 mm in diameter followed by embolization by numerous spring coils. At that time, a partial monorail technique was newly devised to carry the large metallic spider into the feeding artery, otherwise the spider could not pass into a 9F catheter. After embolization, symptoms and PaO2 in arterial blood improved remarkably in both cases. In the second case, a spring coil migrated into the normal pulmonary artery, but no infarction resulted. In conclusion, the metallic spider was very useful for embolization of hugee pulmonary AVF to avoid the embolus passing through and to tangle spring coils together with it. If commercially available "spiders" are too small, ones can be made easily. PMID- 1508655 TI - [MR imaging of corpus callosal injuries]. AB - The MR imaging and CT findings of corpus callosal injury were analyzed in 32 of 224 patients with acute head injuries. MR imaging was more sensitive than CT in the detection of callosal injuries. All 9 hemorrhagic lesions were visualized on both MR imaging and CT. Fifteen of 23 nonhemorrhagic lesions were not visualized on CT, although all nonhemorrhagic lesions were visualized on MR imaging. Twenty four lesions of the corpus callosum were located in the splenium, but no lesion was located in the rostrum. Diffuse axonal shear injuries were visualized in 25 patients with callosal injury as associated traumatic lesions. Twenty-three patients with callosal injury had low initial Glasgow Coma Scale scores (less than 9), but 9 patients had high scores. Associated diffuse axonal shear injuries, especially in the brain stem could be a possible explanation for this difference. MR imaging is useful to detect traumatic lesions of the corpus callosum. PMID- 1508656 TI - [Experimental and clinical study of arterial damage induced by anti-cancer drug infusion]. AB - In order to reduce the arterial damage following arterial chemo-infusion, arterial reaction to anti-cancer drugs and Corticosteroid were studied experimentally and clinically. In experiment, chemo-infusions (Mitomycin C, Adriamycin, Cisplatin) with or without Corticosteroid were carried out into the auricular and femoral arteries of rabbits, and the arterial changes were examined angiographically and histopathologically. The histologic examination showed the damages of various degrees characterized by intimal edema with pyknosis of endothelial cells, thrombus formation and detachment of intimal layer. The degree and frequency of the damage increased as the drug dose and concentration increased. However, higher blood flow and Corticosteroid could reduce the damages in some degrees. Clinically, bronchial arterial infusion of Cisplatin with or without Corticosteroid were studied. In conclusion, when angiography following ACI reveals narrowing and/or irregularity of the target artery, reduction of drug concentration and dose as well as elongation of infusion intervals are advised. PMID- 1508657 TI - [MR imaging of the seminal vesicles--correlations between age, size and signal intensity]. AB - MR findings of 82 cases without seminal vesicle lesions were retrospectively evaluated to assess the mutual correlations between age, size and signal intensity of the seminal vesicle. MR findings of 31 cases of carcinomatous invasion to the seminal vesicle were also evaluated as a control group for low signal intensity area-study. 1.5T superconductive unit (Toshiba 2000FX-II) was used to obtain T1-weighted (SE500/13) and T2-weighted (SE2500/80) images. Significant correlations were noted between age, short-axis diameter of the seminal vesicle and global signal intensity of the seminal vesicle on T2-weighted images. In the study of low signal intensity area on T2-weighted images, diffuse strand-like low signal intensity areas were occasionally seen in cases without seminal vesicle lesions. On the other hand, low signal intensity areas in cases of carcinomatous invasion to the seminal vesicle tended to be more localized and nodular. MR evaluation of cases without seminal vesicle lesions is important not only to delineate physiological changes of the seminal vesicle, but also to avoid erroneous MR-diagnosis of seminal vesicle lesions. PMID- 1508658 TI - [Acute non-opacified dissection of the ascending thoracic aorta--significance of retrograde dissection and re-dissection]. AB - Thirteen cases of acute aortic dissection with non-opacified false lumen of the ascending aorta were examined by CT and other imaging modalities. On the basis of the initial CT findings, these cases were classified into two types; one was pure non-opacified dissection not associated with opacified false lumen (Type N, n = 7), the other was non-opacified dissection of the ascending aorta associated with opacified false lumen of the following aorta (Type N+O, n = 6). On examining the relation between the entry site and the false lumen in Type N+O, the dissection of the ascending aorta was considered to be retrograde. Retrograde dissection seemed to be an important factor in the development of the non-opacified dissection of the ascending aorta. During the follow-up period, re-dissection in the ascending aorta occurred in four of the 13 cases (Type N = 3, Type N+O = 1). The re-dissection occurred within the first four weeks in all of them, and the diagnosis of re-dissection was possible at its early stage. In one case, ulcerlike projection (ULP) was detected by aortography. In another case, ULP was identified by cine-MR imaging. Contrast CT also revealed enlargement and small opacification of the false lumen. In two other cases, similar CT findings were observed. Three of the four patients recovered by surgical treatment. One died the day after the diagnosis of re-dissection. Early diagnosis and earliest possible surgical intervention for re-dissection were considered necessary to save the patients with re-dissected false lumen in the ascending aorta. Close observations with several imaging modalities, mainly CT examination, should be paid in the patients with non-opacified dissection of the ascending aorta for at least four weeks after the onset of dissection. PMID- 1508659 TI - [Conformation radiotherapy of carcinoma of the prostate]. AB - During the period from 1975 to 1989, 84 patients with carcinoma of the prostate were treated with conformation radiotherapy at Tokyo Metropolitan Komagome Hospital. The radiation field encompassed only the area of the prostate gland; it did not include the pelvic lymph nodes. The clinical stage of the 84 tumors was 22 in Stage A, 31 in Stage B, 15 in Stage C and 16 in Stage D. The average age of patients was 73.4 years, with range of 54 to 88 years. The average dose to the tumor was 65.7 Gy, with range of 60 Gy to 70 Gy. Hormone therapy was applied to 42 cases. The 5- and 10-year cumulative survival rates were 90.7% and 70.5% for Stage A, 41.7% and 26.7% for Stage B, 48.9% and 48.9% for Stage C, and 32.6% and 0% for Stage D, respectively. The 5-year cause-specific cumulative survival rates were 100% for Stage A, 92.3% for Stage B, 65.0% for Stage C and 40.3% for Stage D, respectively. Patients with poorly differentiated adenocarcinomas or undifferentiated carcinomas showed poorer survival than those with well differentiated carcinoma. Only 7 cases suffered in-field recurrence, and 2 cases suffered recurrence at pelvic lymph nodes. Acute reactions were noted in 13 cases. Late complications following treatment were acceptable. Mild to moderate complications were recognized in 2 cases, but neither patient required surgery. In conclusion, our data suggest the advantage of the conformation technique applied to radiation therapy for carcinoma of the prostate. PMID- 1508660 TI - Development of substance abuse policies in health care settings. PMID- 1508661 TI - NP/CNS's prepare for certification but can they suture? PMID- 1508662 TI - Comparing nursing students to women students in other disciplines provides insight into the "autonomy problem" experienced by practicing nurses. PMID- 1508663 TI - Selecting and writing bibliographies. PMID- 1508664 TI - 3rd party payment for nurses. PMID- 1508665 TI - Targeting of the creatine kinase M gene in embryonic stem cells using isogenic and nonisogenic vectors. AB - Replacement vectors with genomic DNA originating from different mouse strains were used to introduce site-specific mutations into the creatine kinase M (CKM) gene of mouse embryonic stem (ES) cells. Here we demonstrate that in mouse strain 129-derived ES cells, the gene is at least 25-fold more efficiently targeted with an isogenic, 129-derived vector (129-pRV8.3) than with a nonisogenic, BALB/c specific vector (BALB/c-pRV8.3). The two targeting constructs were identical except for allelic differences which were typed by partial sequencing. These included base pair mismatches (2%) and a polymorphic [GTC]-repeat length variation. Both in separate transfections as well as in cotransfections with mixed vectors, homologous disruption of the CKM gene resulted uniquely from the 129-isogenic DNA. Our data confirm earlier observations on requirements for homologous recombination in pro- and eukaryotic systems and indicate that targeting of the CKM locus is highly sensitive to small sequence differences between cognate segments in the endogenous and incoming DNA. PMID- 1508666 TI - Thioredoxin regulates the DNA binding activity of NF-kappa B by reduction of a disulphide bond involving cysteine 62. AB - A role for redox regulation in activation of the NF-kappa B transcription factor was suggested by the observation that DNA binding activity of free protein, but not preformed DNA-protein complex, is inhibited by -SH modifying agents but enhanced by reducing agents. Mutagenesis of conserved cysteine residues in the p50 subunit identified amino acid 62 as being important for DNA binding, as a serine substitution at this position reduces DNA binding affinity, but renders the protein insensitive to -SH modifying agents. DNA binding activity of the wild type protein but not the amino acid 62 mutant was also stimulated by thioredoxin while detection of disulphide cross linked dimers in p50 but not the amino acid 62 mutant suggests that thioredoxin stimulates DNA binding by reduction of a disulphide bond involving cysteine 62. The physiological relevance of these findings was supported by the observation that cotransfection of a plasmid expressing human thioredoxin and an HIV LTR driven reporter construct resulted in an NF-kappa B dependent increase in expression of the reporter gene. Thus modification of p50 by thioredoxin, a gene induced by stimulation of T lymphocytes in parallel with NF-kappa B translocation, is a likely step in the cascade of events leading to full NF-kappa B activation. PMID- 1508667 TI - In-cell PCR from mRNA: amplifying and linking the rearranged immunoglobulin heavy and light chain V-genes within single cells. AB - We describe a process for the identification of mRNAs within single cells, as demonstrated with the immunoglobulin (Ig) variable region (V) genes of two mouse hybridoma cell lines and the bcr-abl fusion gene of the human K562 myeloid leukaemia line. The cells were fixed and permeabilised, the mRNA reverse transcribed to cDNA and the cDNA amplified by the polymerase chain reaction (PCR). After using fluorescent PCR primers, the amplified DNA could be detected within the cells as demonstrated by confocal fluorescence microscopy and flow cytometry. Furthermore the amplified Ig VH and VL DNA could be assembled within the same cell using suitable PCR primers. We detected no cross-contamination of amplified DNA between cells: the DNA isolated from mixtures of two hybridoma cell lines (B1-8 and NQ10/12.5) treated to in-cell PCR and assembly, was shown by cloning to correspond to the combinations of VH and VL genes of the parent hybridomas. We forsee diverse applications of in-cell assembly by PCR, especially for the analysis of the combinations of chains of rearranged Ig or T cell receptor (TCR) V-genes in a population of cells, and the construction of human antibodies from the V-genes of immune B-lymphocytes. PMID- 1508668 TI - Effects of antioestrogens on the DNA binding activity of oestrogen receptors in vitro. AB - We have investigated the effect of a series of steroidal oestrogen antagonists, related to ICI 164,384, on the DNA binding activity of mouse oestrogen receptors expressed in insect cells. The analogues possess different side chains at the 7 position of the B ring in the steroid. Inhibition was observed when the length of the side-chain was 15-16 carbon atoms but not 10 or 20 carbon atoms and only when the 7 alpha isomer was used. The DNA binding activity of receptors expressed in COS-1 cells was also inhibited after extended periods of incubation with antioestrogens but not that of the human receptor in breast cancer cell-extracts. We have proposed that ICI 164,384 might disrupt receptor dimerisation, and therefore the variation in its ability to inhibit DNA binding activity may reflect differences in dimer stability. Since the DNA binding activity of in vitro translated receptors was inhibited when they were translated in the presence of the antioestrogen we suggest that ICI 164,384 might prevent the formation of receptor dimers without necessarily being able to disrupt preformed dimers. PMID- 1508669 TI - Structure of the human DNA ligase I gene. AB - The gene encoding DNA ligase I, the major DNA ligase activity in proliferating mammalian cells, maps to human chromosome 19q13.2-13.3. We have determined the complete structure of the gene, which is composed of 28 exons spanning 53kb on this chromosome. The first exon is untranslated, and utilises a GC dinucleotide instead of the canonical GT splice donor. The 5' flanking region lacks a TATA box and is highly GC-rich, as is characteristic of a 'housekeeping' gene. In common with the promoters of genes encoding other DNA replication enzymes, such as DNA polymerase alpha, the 5' flanking region of the DNA ligase I gene contains recognition elements for several transcription factors which may mediate increased expression in quiescent cells in response to growth factors. PMID- 1508670 TI - Role of an upstream open reading frame in the translation of polycistronic mRNAs in plant cells. AB - The influence of an upstream small open reading frame (URF) on the translation of two consecutive coding regions on an eukaryotic mRNA was studied. The cis effects of leader length, URF length, the sequences of the URF and neighboring regions, and the trans effects of the Cauliflower mosaic virus transactivator (TAV) were analyzed. Translation efficiency of the immediate downstream open reading frame (ORF) decreased with increasing URF length. Short URFs did not drastically inhibit translation of immediate downstream ORFs but supported far downstream translation in the presence of TAV. In the latter case, the optimal URF length was 30 codons. PMID- 1508671 TI - The vacuum UV CD spectra of G.G.C triplexes. AB - Vacuum UV circular dichroism (CD) spectra were measured down to 175 nm for d(C)10, d(G)10, the d(G)10.d(C)10 duplex, and the d(G)10.d(G)10.d(C)10 triplex. A CD difference spectrum was calculated for d(G)10.d(C)10 giving the change in CD induced by forming the duplex from d(G)10 and d(C)10. The d(G)10.d(G)10.d(C)10 CD difference spectrum gave the CD induced by triplex formation from binding of d(G)10 to the d(G)10.d(C)10 duplex. In the near-UV, the d(G)10.d(C)10 and d(G)10.d(G)10.d(C)10 difference spectra resembled the difference spectrum for poly[r(G).r(C)] (Biopolymers 29, 325-333). This similarity may be an indication of similar purine base stacking. The d(G)10.d(G)10.d(C)10 vacuum UV difference spectrum had a negative band at 195 nm and a positive band at 180 nm, making it similar to difference spectra for homopolymer triplexes containing T.A.T and U.A.U triplets (Nucl. Acids Res. 19, 2275-2280). The appearance of these bands in difference spectra should be good indicators of triplex formation. The complementary oligonucleotides c-mycI d(CCCCACCCTCCC) and c-mycII d(GGGAGGGTGGGG) are part of the regulatory sequences of the human c-myc gene. G.G.C rich triplexes formed by binding c-mycII or c-mycIII d(GGGGTGGGTGGG) to the c-mycI.c mycII duplex had CD difference spectra similar to that of d(G)10.d(G)10.d(C)10 in both the vacuum UV and near UV regions, indicating similar triplet structures. PMID- 1508672 TI - Transcriptional induction of IFN-gamma-responsive genes is modulated by DNA surrounding the interferon stimulation response element. AB - The 9/27 and GBP mRNAs are both inducible by Interferon-gamma (IFN-gamma). The promoters of both genes contain an Interferon Stimulation Response Element (ISRE), but while the GBP gene is strongly induced transcriptionally by IFN-gamma the response of the 9/27 promoter is very weak. We investigated the molecular basis for this difference. The different IFN-gamma-responsiveness was found to have more than one reason. First, 9/27 promoter DNA was unable to bind the Gamma Interferon Activation Factor (GAF) with a single high affinity site. It efficiently competed for the association of the GAF with the GBP promoter but this competition was due to the presence of two low affinity sites, the ISRE and an ISRE-like sequence, suggesting that the GAS and ISRE, though both having clear preferences for specific proteins, may nevertheless share a certain degree of structural homology. Second, the 9/27 and GBP ISREs differed markedly in their affinities for regulatory proteins (ISGFs 1,2,3) and the GBP ISRE was more potent in mediating IFN-gamma-induced promoter activity in transient transfection. Third and most importantly, however, the strong difference between the IFN-gamma response of the two promoters was mainly due to the sequences surrounding the ISRE: the positive-acting GAS on one side and sequences with silencing properties 5' and 3' of the 9/27 ISRE on the other side. The data thus show mechanisms to both up- and down-regulate the activity of the ISRE. PMID- 1508673 TI - A role for the human single-stranded DNA binding protein HSSB/RPA in an early stage of nucleotide excision repair. AB - The human single-stranded DNA binding protein (HSSB/RPA) is involved in several processes that maintain the integrity of the genome including DNA replication, homologous recombination, and nucleotide excision repair of damaged DNA. We report studies that analyze the role of HSSB in DNA repair. Specific protein protein interactions appear to be involved in the repair function of HSSB, since it cannot be replaced by heterologous single-stranded DNA binding proteins. Anti HSSB antibodies that inhibit the ability of HSSB to stimulate DNA polymerase alpha also inhibit repair synthesis mediated by human cell-free extracts. However, antibodies that neutralize DNA polymerase alpha do not inhibit repair synthesis. Repair is sensitive to aphidicolin, suggesting that DNA polymerase epsilon or delta participates in nucleotide excision repair by cell extracts. HSSB has a role other than generally stimulating synthesis by DNA polymerases, as it does not enhance the residual damage-dependent background synthesis displayed by repair-deficient extracts from xeroderma pigmentosum cells. Significantly, when damaged DNA is incised by the Escherichia coli UvrABC repair enzyme, human cell extracts can carry out repair synthesis even when HSSB has been neutralized with antibodies. This suggests that HSSB functions in an early stage of repair, rather than exclusively in repair synthesis. A model for the role of HSSB in repair is presented. PMID- 1508674 TI - Identification of a novel downstream binding protein implicated in late-phase specific activation of the adenovirus major late promotor. AB - The adenovirus major late promotor (MLP) is induced to very high levels after the onset of the viral DNA replication. Previous studies have identified sequence elements located downstream of the MLP startsite (DE1, between +85 and +98; DE2, between +100 and +120) implicated, together with the upstream promoter element, in this late-phase-specific transcriptional activation. One protein (DEF, now renamed DEF-A), induced during the late phase of viral infection, has been identified and shown to bind to the DE1 element (Jansen-Durr et al., 1989, J. Virol. 63, 5124-5132). Here we report about a distinct late-phase-specific protein (DEF-B) and its interactions with DEF-A. DNA-binding studies reveal that DEF-B interacts with the 5' part of DE2 (DE2b), whereas DEF-A, besides its interaction with DE1, also binds to the 3' portion of DE2 (DE2a), but with a lower affinity than for DE1. Furthermore, when added together, DEF-A and DEF-B cooperatively assemble onto the DE2 element as a heteromeric complex which is substantially more stable than the complexes formed by each protein alone. Using an in vivo transcriptional assay of the MLP, we show that DEF-A and DEF-B both have intrinsic transactivating properties. PMID- 1508675 TI - Extraordinarily stable mini-hairpins: electrophoretical and thermal properties of the various sequence variants of d(GCGAAAGC) and their effect on DNA sequencing. AB - A small DNA fragment having a characteristic sequence d(GCGAAAGC) has been shown to form an extraordinarily stable mini-hairpin structure and to have an unusually rapid mobility in polyacrylamide gel electrophoresis, even when containing 7M urea. Here, we have studied the stability of the various sequence variants of d(GCGAAAGC) and the corresponding RNA fragments. Many such sequence variants form stable mini-hairpins in a similar manner to the d(GCGAAAGC) sequence. The RNA fragment, r(GCGAAAGC) also forms a mini-hairpin structure with less stability. The DNA mini-hairpins with GAAA or GAA loop are much more stable than DNA and RNA mini-hairpins with other loop sequence so far as has been examined. The stability difference between DNA and RNA mini-hairpins may be deduced to the stem structures formed by DNA (B form) and RNA (A form). The stable hairpins consisting of the GCGAAAGC sequence cause strong band compression on the sequencing gel. This phenomenon should be carefully considered in DNA sequencing. PMID- 1508676 TI - Purification and characterization of DNA ligase I from the trypanosomatid Crithidia fasciculata. AB - A DNA ligase has been purified approximately 5000-fold, to near homogeneity, from the trypanosomatid Crithidia fasciculata. The purified enzyme contains polypeptides with molecular masses of 84 and 80 kDa as estimated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Both polypeptides formed enzyme-adenylate complexes in the absence of DNA, contained an epitope that is highly conserved between human and bovine DNA ligase I and yeast and vaccinia virus DNA ligases, and were identified in fresh lysates of C. fasciculata by antibodies raised against the purified protein. Hydrodynamic measurements indicate that the enzyme is an asymmetric protein of approximately 80 kDa. The purified DNA ligase can join oligo(dT) annealed to poly(dA), but not oligo(dT) annealed to poly(rA), and can ligate blunt-ended DNA fragments. The enzyme has a low Km for ATP of 0.3 microM. The DNA ligase absolutely requires ATP and Mg2+, and is inhibited by N-ethylmaleimide and by KCI. Substrate specificity, Km for ATP, and the conserved epitope all suggest that the purified enzyme is the trypanosome homologue of DNA ligase I. PMID- 1508677 TI - Random mutations to evaluate the role of bases at two important single-stranded regions of genomic HDV ribozyme. AB - In elucidating function of two important single-stranded regions [SSrA (726-731 nt) and SSrB (762-766 nt)] derived mainly from three secondary structure models in genomic hepatitis delta virus (HDV) ribozyme possessing self-cleavage activity, we have constructed several random mutants at those two regions on the HDV88 molecule (683-770 nt) by oligonucleotide-directed mutagenesis. When self cleavage activities were compared among mutants, at the region SSrA, G726 was found to play an important role during cleavage reaction since substitutions of the base to A (mutant A20) or C (mutant A16) or U (mutant A23), reduced the ribozyme activity to very low levels suggesting the importance of G726 position. C763 at SSrB region was found to play a more significant role during catalysis than G726 (at region SSrA) since any substitutions at C763 completely inactivated the ribozyme. Other bases located in these two regions could be substituted to other bases at the expense of some self-cleavage activity. The results presented here together with our previous deletion analysis indicate that these two regions may play an important role during cleavage process. PMID- 1508678 TI - Molecular cloning of RAD16, a gene involved in differential repair in Saccharomyces cerevisiae. AB - We have cloned the RAD16 gene of Saccharomyces cerevisiae and determined its nucleotide sequence. The gene complements the UV sensitivity of a rad16 mutant and restores the ability to repair the transcriptionally inactive HML alpha locus that is absent in this mutant. Disruption mutants that were constructed using the cloned gene are viable and UV sensitive and show no detectable growth defect. Moreover, such a mutant is deficient for repair of the HML alpha locus. The nucleotide sequence shows that the gene codes for a protein of 790 amino acids that has two potential zinc binding domains and shares homology with two other yeast proteins: the RAD54 gene product involved in recombinational repair and SNF2, a transcription factor that possibly functions in transcription activation through an interaction with chromatin components that allows access of other factors involved in transcription. The role of RAD16 in the repair of HML alpha might be to change the chromatin structure of silenced genes to provide access for excision repair enzymes. PMID- 1508679 TI - Crosstalk between plasmid vegetative replication and conjugative transfer: repression of the trfA operon by trbA of broad host range plasmid RK2. AB - Previous deletion and complementation analysis has indicated that the region between trfA and kilBI (trbB) encodes trans-acting factor, designated trbA, required for conjugative transfer of broad host range plasmid RK2. In analysing the nucleotide sequence of this region we have discovered a gene encoding a 12 kDa polypeptide. The predicted amino acid sequence of this protein shows similarity at its C-terminal to KorA from the central control operon of RK2 and at its N-terminal to immunity repressor protein from phage phi 105 of Bacillus subtilis as well as the Sin protein of B. subtilis which regulates alternate developmental processes including sporulation, motility and competence. We show that TrbA represses transcription of both trfA (vegetative replication) and kilBI (trbB) (required for conjugative transfer and whose product has similarity to ComG, required for competence of B. subtilis) and may help to coordinate expression of both sets of functions. This region has similarities to some temperate bacteriophage immunity regions in modulating divergent transcription required for alternative means of propagation. PMID- 1508680 TI - Enhancement of ribosomal frameshifting by oligonucleotides targeted to the HIV gag-pol region. AB - The pol gene of all retroviruses is expressed as a gag-pol fusion protein which is proteolytically processed to produce all viral enzymes. In the human immunodeficiency virus (HIV), the gag and pol genes overlap by 241 nucleotides with pol in the -1 phase with respect to gag. The gag-pol fusion is produced via a -1 ribosomal frameshifting event that brings the overlapping, out-of-phase gag and pol genes into translational phase. Frameshifting occurs at a so called 'shift site' 8-10 nucleotides upstream of a hairpin loop which may play a role in the regulation of frameshifting. We have fused this region of HIV-1 to the 5' end of the firefly luciferase reporter gene in order to quantitatively measure ribosomal frameshifting both in cells and by in vitro translation. A series of 2' O-methyl oligonucleotides was designed to specifically bind the sequences which flank the gag-pol hairpin. Ribosomal frameshifting is enhanced up to 6 fold by those oligonucleotides which bind the area just 3 to the stem. Oligonucleotides which bind 5' to the stem have no effect on frameshift efficiency. In addition, we have constructed a series of fusion genes which mimic the effect of the bound oligonucleotides with intramolecular hairpins. The results suggest that increasing RNA secondary structure downstream of the shift site increases the frequency of ribosomal frameshifting, and that this effect can be mimicked by antisense oligonucleotides. PMID- 1508681 TI - Evidence for a HeLa cell splicing activity that is necessary for activation of a regulated adenovirus 3' splice site. AB - Adenovirus late region 1 pre-mRNA splicing is temporally regulated during a lytic infection at the level of alternative 3' splice site usage to produce two mRNAs; the 52,55K and IIIa mRNAs which utilize the proximal and distal 3' splice sites, respectively. In vivo, the 52,55K mRNA is produced both early and late after infection, while IIIa is produced exclusively late in infection. Uninfected HeLa cell nuclear extracts, prepared with a low salt (0.4-0.5 M) or high salt (0.6 M and higher) wash, differed in their ability to splice 52,55K, IIIa and beta globin transcripts. 52,55K and beta-globin precursors were spliced with similar efficiency in the low and high salt extract, while the IIIa mRNA was generated only in the high salt extract. Using the beta-globin pre-mRNA, no kinetic differences between the two types of extracts were observed. Nor were there any significant differences in the snRNA composition. The IIIa splicing activity did not appear to correlate with U2AF and pPTB levels. Our results suggest that a cellular trans-acting factor(s), which is required for adenovirus IIIa 3' splice site activation, is solubilized only at high salt concentrations. PMID- 1508682 TI - Gene rescue in plants by direct gene transfer of total genomic DNA into protoplasts. AB - To study the possibility of gene rescue in plants by direct gene transfer we chose the Arabidopsis mutant GH50 as a source of donor DNA. GH50 is tolerant of chlorsulfuron, a herbicide of the sulfonylurea class. Tobacco protoplasts were cotransfected with genomic DNA and the plasmid pHP23 which confers kanamycin resistance. A high frequency of cointegration of the plasmid and the genomic DNA was expected, which would allow the tagging of the plant selectable trait with the plasmid DNA. After transfection by electroporation the protoplasts were cultivated on regeneration medium supplemented with either chlorsulfuron or kanamycin as a selective agent. Selection on kanamycin yielded resistant calluses at an absolute transformation frequency (ATF) of 0.8 x 10(-3). Selection on chlorsulfuron yielded resistant calluses at an ATF of 4.7 x 10(-6). When a selection on chlorsulfuron was subsequently applied to the kanamycin resistant calluses, 8% of them showed resistance to this herbicide. Southern analysis carried out on the herbicide resistant transformants detected the presence of the herbicide resistance gene of Arabidopsis into the genome of the transformed tobacco. Segregation analysis showed the presence of the resistance gene and the marker gene in the progeny of the five analysed transformants. 3 transformants showed evidence of genetic linkage between the two genes. In addition we show that using the same technique a kanamycin resistance gene from a transgenic tobacco could be transferred into sugar beet protoplasts at a frequency of 0.17% of the transformants. PMID- 1508683 TI - Atomic force microscopy of reovirus dsRNA: a routine technique for length measurements. AB - Atomic force microscopy (AFM) was used to image reovirus double stranded RNA (dsRNA) deposited from diluted buffer solution onto a chemically treated mica surface. This procedure allows AFM images of dsRNA molecules to be obtained with a quality close to that obtained with conventional electron microscopy. The length of the molecules were measured directly on a computer display using the digitally acquired images. The lengths of the molecules varied between 0.2 and 1.8 microns. Statistical analysis showed a multimodal distribution with clear maxima at 0.4, 0.65 and 1.05 microns. These data are in a good agreement with those obtained by electron microscopy and gel electrophoresis. PMID- 1508684 TI - Intronic sequence with both negative and positive effects on the regulation of alternative transcripts of the chicken beta tropomyosin transcripts. AB - The chicken beta tropomyosin gene generates three major transcripts by alternative splicing. A pair of internal exons are spliced in a mutually exclusive manner and their utilisation is developmentally regulated. Exon 6A and exon 6B are used respectively in myoblasts and myotubes during the process of differentiation of muscle cells. We have previously reported that, in myoblasts, exon 6B is skipped because of a negative regulation which involves intron as well as exon sequences. In this report, we describe a previously uncharacterized intronic element which is involved in the regulation of the splicing of both exons 6A and 6B. This cis-element is localized 37nt downstream of exon 6A and is approximately 30nt long. Its deletion, as well as modification of its sequence, results in the activation of the use of exon 6B and, at the same time, in the inhibition of the use of exon 6A. The mechanisms by which this region could act are further discussed. PMID- 1508685 TI - Solid-phase synthesis of the nucleopeptide fragment H-Asp-Ser[pAAAGTAAGCC]-Glu-OH from the nucleoprotein of Bacillus subtilis phage phi 29. AB - The naturally occurring DNA-nucleopeptide H-Asp-Ser[5'-pAAAGTAAGCC-3']-Glu-OH was prepared via a solid-phase phosphite triester approach using N-2-(tert butyldiphenylsilyloxymethyl)benzoyl protected nucleosides. The oligonucleotide was linked via the extremely base-labile oxalyl ester anchor to the solid support. PMID- 1508686 TI - Intron 1 and the 5'-flanking region of the human thymidylate synthase gene as a regulatory determinant of growth-dependent expression. AB - We have determined the regulatory regions responsible for the growth-dependent expression of the human thymidylate synthase (TS) gene, using a set of minigenes constructed from segments of the human TS gene and the cDNA clone. Each construct was introduced stably into a TS-negative mutant of rat fibroblast 3Y1 cells. By serum-restricted synchronization of the cloned transformant cells, we found that a minigene with the genomic 5'-flanking region and intron 1 without other introns were sufficient for the normal extent and pattern of S-phase specific expression at the levels of both mRNA and enzymatic activity. In contrast, a TS cDNA clone driven by an SV40-based expression vector showed constitutive expression. Insertion of intron 1 into the cDNA clone in the normal location, or replacement of the viral 5'-promoter region of the cDNA clone by the genomic 5'-flanking sequence converted the constitutive expression to the S-phase dependent one, but only partly, that is, coexistence of the two regions were required for the normal expression. Results obtained by nuclear run-on assay suggested that posttranscriptional controls are also involved in this regulation in consistent with our previous results with the bona fide human TS gene. PMID- 1508688 TI - Characterization of Arabidopsis thaliana telomeres isolated in yeast. AB - In an effort to learn more about the genomic organization of chromosomal termini in plants we employed a functional complementation strategy to isolate Arabidopsis thaliana telomeres in the yeast, Saccharomyces cerevisiae. Eight yeast episomes carrying A. thaliana telomeric sequences were obtained. The plant sequences carried on two episomes, YpAtT1 and YpAtT7, were characterized in detail. The telomeric origins of YpAtT1 and YpAtT7 insert DNAs were confirmed by demonstrating that corresponding genomic sequences are preferentially degraded during exonucleolytic digestion. The isolated telomeric restriction fragments contain G-rich repeat arrays characteristic of A. thaliana telomeres, as well as subterminal telomere-associated sequences (TASs). DNA sequence analysis revealed the presence of variant telomeric repeats at the centromere-proximal border of the terminal block of telomere repeats. The TAS flanking the telomeric G-rich repeat in YpAtT7 corresponds to a repetitive element present at other A. thaliana telomeres, while more proximal sequences are unique to one telomere. The YpAtT1 TAS is unique in the Landsberg strain of A. thaliana from which the clone originated; however, the Landsberg TAS cross-hybridizes weakly to a second telomere in the strain Columbia. Restriction analysis with cytosine methylation sensitive endonucleases indicated that both TASs are highly methylated in the genome. PMID- 1508687 TI - Exon sequences distant from the splice junction are required for efficient self splicing of the Tetrahymena IVS. AB - The presence of a natural rRNA secondary structure element immediately preceding the 5' splice site of the Tetrahymena IVS can inhibit self-splicing by competing with base pairing between the 5' exon and the guide sequence of the IVS (P1). Formation of this alternative hairpin is preferred in short precursor RNAs, and results in loss of G-addition to the 5' splice site. Pre-rRNAs which contain longer exons of ribosomal sequence, however, splice rapidly. As many as 146 nucleotides of the 5' exon and 86 nucleotides of the 3' exon are required for efficient self-splicing of Tetrahymena precursors. The presence of nucleotides distant from the 5' splice site apparently alters the equilibrium between the alternative hairpins, and promotes formation of active precursors. This effect is dependent on the specific sequences of the ribosomal pre-RNA, since point mutations within this region reduce the rate of splicing as much as 50-fold. This system provides an opportunity to study the way in which long-range interactions can influence splice site selection in a highly structured RNA. PMID- 1508689 TI - Trans replication and high copy numbers of wheat dwarf virus vectors in maize cells. AB - The replication of shuttle vectors derived from Wheat Dwarf Virus, a monopartite geminivirus, was studied in cultured maize endosperm cells, and in the Black Mexican Sweet (BMS) maize cell line. Using in vivo labeling and DNA methylation analysis, we showed that replication was initiated within 24 hrs after transfection, and did not require cell division in both cell lines. Copy numbers of 30,000 ds DNA molecules per cell were observed in endosperm cells after three days. The replication protein was shown to act in trans, since the wild type gene of the shuttle vector enabled replication-deficient vectors carrying mutated genes to replicate. These properties suggest that WDV may have similar applications in plants as SV40 in mammalian cells. PMID- 1508690 TI - An ultraviolet light-induced crosslink in yeast tRNA(Phe). AB - The irradiation of native or unmodified yeast tRNA(Phe) by short wavelength UV light (260 nM) results in an intramolecular crosslink that has been mapped to occur between C48 in the variable loop and U59 in the T loop. Photo-reversibility of the crosslink and the absence of fluorescent photo adducts suggest that the crosslink product is a cytidine-uridine cyclobutane dimer. This is consistent with the relative geometries of C48 and U59 in the crystal structure of yeast tRNA(Phe). Evaluation of the crosslinking efficiency of the mutants of tRNA(Phe) indicates that the reaction depends on the correct tertiary structure of the RNA. PMID- 1508691 TI - Hairpin and parallel quartet structures for telomeric sequences. AB - The role of thymine residues in the formation of G-quartet structures for telomeric sequences has been investigated using model oligonucleotides of the type d(G4TnG4), with n = 1-4. Sequences d(G4T3G4) and d(G4T4G4) adopt a G-quartet structure formed by hairpin dimerization in 70 mM NaCl as judged by a characteristic circular dichroism signature with a 295 nm positive and 265 nm negative bands while d(G4TG4) adopts a parallel G-quartet structure like d(G12) which exhibits a strong positive band at 260 nm and a negative band at 240 nm. The sequence d(G4T2G4) exhibits a mixture of both conformations. The stability of hairpin G-quartet structures decreases with decrease in the number of intervening thymine residues. Potassium permanganate, a single strand specific probe has been used to establish the presence of loops composed of T residues in the hairpin G quartet structures formed by the oligonucleotides d(G4TnG4) with n = 2-4 in 70 mM NaCl. The formation of hairpin G quartet structure for the above sequences is further supported by the enhanced electrophoretic mobility observed on non denaturing polyacrylamide gels. Human telomeric sequence d(TTAGGG)4 which showed enhanced electrophoretic mobility like Tetrahymena telomeric sequence d(T2G4)4 also exhibited a characteristic CD spectrum for a folded-back G-quartet structure. A detailed model for G-quartet structure involving hairpin dimer with alternating syn-anti-syn-anti conformation for the guanine residues both along the chain as well as around the G tetrad with at least two thymine residues in the loop is proposed. Intermolecular association of short telomeric sequences reported here provides a possible model for chromosomal pairing. PMID- 1508693 TI - Nucleotide sequence of the gene coding for ribosomal protein S10 from the archaeum Thermoplasma acidophilum. PMID- 1508692 TI - Repression of the basal c-fos promoter by wild-type p53. AB - Mutations in the p53 gene are the most common genetic alterations observed in many inherited and sporadic forms of human cancer. Recent studies indicate that wild-type p53 may be involved in the regulation of gene expression. In the present report we examined the effect of p53 on the human c-fos promoter. Using a transient co-transfection assay we show that wild-type human p53, but not a transforming mutant of p53, negatively regulates the activity of the c-fos promoter in a dose-dependent manner. Promoter deletion analysis maps a sequence conferring p53 repression to the basal promoter region between nucleotides -53 and +42 relative to the cap site. In contrast, p53 strongly stimulates transcription when a sequence previously reported to bind p53 (TGCCT repeat) was inserted in front of the HSV-TK promoter driving CAT. These findings raise the question as to whether p53 may mediate its inhibitory effect on c-fos gene expression by interfering, directly or indirectly, with components of the basal transcriptional machinery. PMID- 1508694 TI - Molecular cloning of a new guanine nucleotide-exchange protein, EF1 delta. PMID- 1508695 TI - Isolation and characterization of the hupA gene coding for HU of Aeromonas proteolytica. PMID- 1508696 TI - c/CEPB, a chicken transcription factor of the leucine-zipper C/EBP family [corrected]. PMID- 1508697 TI - Cloning of the gene for ribosomal protein S13 from the fission yeast Schizosaccharomyces pombe. PMID- 1508698 TI - Isolation and sequence of a cDNA encoding the cap binding protein of wheat eukaryotic protein synthesis initiation factor 4F. PMID- 1508699 TI - One pot general method for the derivatisation of polymer support for oligonucleotide synthesis. PMID- 1508700 TI - An improved method for the isolation of chromosomal DNA from various bacteria and cyanobacteria. PMID- 1508702 TI - Rapid mycobacterial plasmid analysis by electroduction between Mycobacterium spp. and Escherichia coli. PMID- 1508701 TI - Rapid isolation of specific DNA-binding proteins and their DNA-binding domains. PMID- 1508703 TI - Rapid transfer of small RNAs from a polyacrylamide gel onto a nylon membrane using a gel dryer. PMID- 1508705 TI - Nucleotide sequence of a new lignin peroxidase gene GLG3 from the white-rot fungus, Phanerochaete chrysosporium. PMID- 1508704 TI - New nucleotide sequence data on the EMBL File Server. PMID- 1508706 TI - Electronic communications and the new biology. PMID- 1508707 TI - Identification of regulatory elements within the minimal promoter region of the human endogenous ERV9 proviruses: accurate transcription initiation is controlled by an Inr-like element. AB - ERV9 is a low repeated family of human endogenous retroviral elements whose expression is mainly detectable in undifferentiated embryonal carcinoma NT2/D1 cells. In this report we have analyzed the minimal promoter region located within the ERV9 LTR. Using the transient CAT expression assay we have identified the minimal promoter region, which includes sequences spanning from -70 to +6 relative to the major transcription start site. Deletion analysis, primer extension mapping of the transcription start sites and DNA-protein interactions assays have allowed us to define two important regions within the ERV9 minimal promoter. One region located between -70 to -39 acts as a transcriptional activating sequence and contains an Sp 1 binding site. The second region from -7 to +6, which resembles an initiator element (Inr), was necessary for the correct transcription start site utilization, and binds to a regulatory protein. Cross competition experiments using various Inr elements have indicated that the protein that binds to the ERV9 Inr element can be competed by the HIV-1 and TdT Inr sequences. PMID- 1508708 TI - Zinc finger-DNA recognition: analysis of base specificity by site-directed mutagenesis. AB - Zinc fingers of the Cys2/His2 class are conserved 28-30 amino acid motifs that constitute an important and widespread family of eukaryotic DNA-binding domains. It is therefore of great interest to understand the rules that govern specific recognition of DNA by zinc fingers. The DNA-binding domain of the transcription factor Krox-20 consists of three zinc fingers, each of them making its primary contacts with a three-base pair subsite. We have performed a data base-guided site-directed mutagenesis analysis of Krox-20: nine derivatives were generated, in which one to three amino acid changes had been introduced within finger 2, at positions which were likely to affect the specificity of DNA recognition. The affinities of the different proteins for a panel of potential DNA binding sites were estimated by gel retardation assay. Six of the derivatives bound specific targets with affinities comparable to that of wild type Krox-20 for its consensus binding site. However, the specificity of recognition was dramatically modified at the expected bases, in a manner that could be explained by examining the newly introduced amino acids within the context of the overall finger/triplet interaction. These data provide new insights into the details of zinc finger-DNA interactions and, combined with the modular nature of zinc fingers, illustrate both the potential and the difficulties of utilising these motifs for designing DNA-binding proteins with novel specificities. PMID- 1508709 TI - Multiple components are involved in the efficient joining of double stranded DNA breaks in human cell extracts. AB - We describe a rapid and efficient in vitro system for the rejoining of double stranded breaks in DNA based on extracts of human 293 cells. Using this system as an assay, we have separated the nuclear extract into several components involved in break rejoining. The unfractionated system can convert approx. 100% of the input DNA, linearized with a restriction enzyme, to high molecular weight material at low temperature (17 degrees C), and at the physiological temperature of 37 degrees C we have shown that competing activities in the extract can also act on the DNA template. We present the fractionation of the extract and the partial purification of a novel factor which will stimulate a crude rejoin activity and in addition increases the activity of purified DNA ligase I. We have also partially purified the break joining activity and show that the chromatographic properties do not directly correspond with the three DNA ligases previously described, indicating that the activity observed may not be due to a single enzyme species. By studying the rejoining of double stranded DNA breaks as a biochemical process, we have demonstrated that the efficient joining of such breaks requires factors in addition to DNA ligases. PMID- 1508710 TI - Structure and expression of the nuclear gene coding for the plastid CS1 ribosomal protein from spinach. AB - The chloroplast ribosomal protein CS1 is an essential component of the plastids translational machinery involved in translation initiation. Southern analysis suggests that the corresponding nuclear gene is present in one copy in the spinach genome. We have isolated and sequenced the gene (rps1) to study its expression at the transcriptional level. The gene consists of 7 exons and 6 introns including an unusually large intron in the 5' coding region. No canonical TATA-box is found in the 5' upstream region of the gene. rps1 transcripts are detected early during germination and a significant accumulation is observed after the protrusion of the radicle. CS1 mRNAs are present in all organs of young seedlings although there are dramatic differences in the steady state level of the mRNAs between leaves and roots tissues. Transcripts accumulate independently of the presence or absence of light. Band shift analysis shows that the +1, -400 bp region of the gene can bind different sets of proteins isolated from roots and leaves nuclei. We suggest that the expression of the housekeeping plastid-related rps1 gene is regulated in a tissue-specific manner by transcriptional trans acting factors. PMID- 1508711 TI - Structure of the phenylalanyl-tRNA synthetase genes from Thermus thermophilus HB8 and their expression in Escherichia coli. AB - A 4459 bp long BamHI restriction fragment containing the two genes for the Thermus thermophilus HB8 phenylalanyl-tRNA synthetase was cloned in Escherichia coli and its nucleotide sequence was determined. The genes pheS and pheT encode the alpha- and beta-subunits with a molecular weight of 39 and 87 kD, respectively. Three conserved sequence motifs typical for class II tRNA synthetases occur in the alpha-subunit. Secondary structure predictions indicate that an arm composed of two anti-parallel alpha-helices similar to that reported for the E.coli seryl-tRNA synthetase may be present in its N-terminal portion. In the beta-subunit clusters of hydrophilic amino acids and a leucine zipper motif were identified, and several pronounced alpha-helical regions were predicted. The particular arginine and lysine residues in the N-terminal portion of the beta subunit, which were found to participate in tRNA binding in the yeast and E.coli PheRSs, have their counterparts in the T.thermophilus protein. The 5'-portion of an open reading frame downstream of pheT was found and codes for a yet unidentified, extremely hydrophobic peptide. The pheST genes are presumably cotranscribed and translationally coupled. A novel type of a putative transcriptional terminator in Thermus species was identified immediately downstream of pheT and other Thermus genes. The genes pheS and pheST were expressed in E.coli. PMID- 1508712 TI - Isolation and characterization of the chicken bcl-2 gene: expression in a variety of tissues including lymphoid and neuronal organs in adult and embryo. AB - The expression of human bcl-2 gene is de-regulated by t(14;18) translocation in most of follicular lymphoma. Recent studies indicated that the bcl-2 gene product has an ability to block apoptosis of hematopoietic cells. To facilitate the analysis of the role of this gene in normal development using an animal model, we have isolated and partially characterized the chicken homologue of human bcl-2 gene. The analysis of nucleotide sequence showed that the organization of the chicken bcl-2 gene is very similar to that of human bcl-2 gene. The primary transcript is spliced to encode a 25,687 dalton (233 a.a.) protein. The chicken Bcl-2 protein has two regions highly homologous to human Bcl-2 protein surrounding a totally non-homologous region. The expression of the chicken bcl-2 gene was analyzed in various chicken tissues. In the adult chicken, bcl-2 transcripts were detected in thymus, spleen, kidney, heart, ovary and brain, with the highest levels being detected in the thymus. However, the bursa of Fabricius, which is the site of early B cell development, expressed much less amounts of bcl 2 RNA. On the other hand, in embryo, the gene is extensively expressed in the bursa, as well as in muscle and the above tissues. Our findings indicate that a homologue of the human bcl-2 gene does exist in the chicken and that its expression is developmentally regulated in some tissues. PMID- 1508713 TI - The promoter of the tgt/sec operon in Escherichia coli is preceded by an upstream activation sequence that contains a high affinity FIS binding site. AB - The tgt/sec operon in E. coli consists of five genes: queA, tgt, ORF12, secD, and secF. QueA and Tgt participate in the biosynthesis of the hypermodified t-RNA nucleoside Queuosine, whereas SecD and SecF are involved in protein secretion. Examination of the promoter region of the operon showed structural similarity to promoter regions of the rrn-operons. An upstream activation sequence (UAS) containing a potential binding site for the factor of inversion stimulation (FIS) was found. Gel retardation assays and DNaseI footprinting indicated, that FIS binds specifically and with high affinity to a site centred at position -58. Binding of FIS caused bending of the DNA, as deduced from circular permutation analysis. Various 5' deletion mutants of the promoter region were constructed and fused to a lacZ reporter gene to determine the influence of the UAS element on the promoter strength. An approximately two-fold activation of the promoter by the UAS element was observed. PMID- 1508714 TI - Cationic lipid-mediated transfection of liver cells in primary culture. AB - We describe transfection of DNA into parenchymal and individual non-parenchymal cell populations from adult rat liver in early primary culture, using cationic lipid as the carrier. All cell populations were transfectable, although lipid requirements varied by cell type and, for hepatocytes, with the age of the culture. For hepatocytes in early primary culture (2-10 hours after plating), pure DOTMA (N-[1-(2,3-dioleyloxy)propyl]-N,N,N-trimethylammonium chloride) was strikingly more effective than commercial formulations (Lipofectin or TransfectACE) containing components in addition to, or other than DOTMA. For hepatocytes fully adapted to culture (approximately 48 hours after plating), pure DOTMA and Lipofectin were similarly effective. Under optimal conditions, about 10% of hepatocytes expressed the transfected reporter gene. CAT expression in hepatocytes doubled from 48 hours to 7 days after transfection. The effect of culture substratum on transfection efficiency also was examined. The presence of basement membrane-like matrix (EHS gel) reduced uptake of the DNA-lipid complex. However, cells in early culture that were transfected on collagen and then replated on EHS gel, displayed significantly greater reporter gene activity than did cells maintained throughout on collagen. In contrast to hepatocytes, non parenchymal cells (lipocytes, Kupffer cells and endothelial cells, respectively) were transfected most efficiently by Lipofectin; DOTMA alone was inactive. The methods described will facilitate studies of gene regulation in individual liver cell populations. PMID- 1508715 TI - Blockage of polymerase-catalyzed DNA chain elongation by chemically modified cytosine residues in templates and the release of blockage for readthrough. AB - The Klenow fragment-mediated in vitro DNA elongation was inhibited by the presence of a class of modified cytosines in the template DNA, i.e., the N4 amino(and -methoxy)-5,6-dihydrocytosine-6-sulfonate residues. We have studied the mechanism of the blockage, using as templates bisulfite-hydrazine (and methoxyamine)- modified single strand phage-M13mp2 DNA and synthetic oligonucleotides. Both N4-amino-5,6-dihydrocytosine-6-sulfonate and N4-methoxy 5,6-dihydrocytosine-6-sulfonate residues blocked the elongation at one nucleotide before these sites. In this blockage, the idling of polymerase at the lesion site due to its 3'-5' exonuclease action appears not to play a major role, because Sequenase that lacks the 3'-5' exonuclease activity still could not readthrough these sites. It seems possible that conformational distortion of the template near these sites is responsible for the blockage, because on conversion of this 5,6-dihydropyrimidine-6-sulfonate structure into a planar pyrimidine, a complete restoration of polymerase-readthrough resulted. In the presence of RecA and SSB proteins, the Klenow fragment was able to partially readthrough these sites. Since there was no decrease in the 3'-5' exonuclease activity during this readthrough, it seems that the binding of these proteins relaxes the distortion in the modified template to allow the polymerase to readthrough the lesion site. These sites on phage DNA can be lethal but also are capable of inducing C-to-T transitions. This observation suggests that these sites can be read by E. coli DNA polymerases in vivo with accompanying errors. PMID- 1508716 TI - The centromere and promoter factor 1 of yeast contains a dimerisation domain located carboxy-terminal to the bHLH domain. AB - CPF1 is a basic helix-loop-helix (bHLH) protein required for optimal centromere function and for maintaining methionine independent growth in yeast. In this work, we show that the region carboxy-terminal to the bHLH domain of CPF1 is essential for CPF1 function in the cell and for dimerisation of CPF1 in solution. The C-terminus of CPF1 contains a potential long amphipathic helix with a hydrophobic face which could provide a suitable protein:protein interface. Point mutations in residues forming this hydrophobic face are sufficient to weaken the interaction between the protein and DNA. By fusing the DNA binding domain or the transcriptional activation domain of GAL4 to the C-terminal 87 amino acids of CPF1, we show that this region is sufficient for mediating protein:protein interactions in vivo. The C-terminal domain of CPF1 can be replaced by the leucine repeat region of the bHLH-ZIP protein USF and the hybrid CPF1-USF protein functions in vivo to provide normal centromere function and methionine independent growth. However, the CPF1-USF hybrid protein is unable to interact with CPF1 suggesting that a dimer of CPF1 is sufficient for maintaining methionine independent growth and normal centromere function. PMID- 1508717 TI - Control of mouse U1a and U1b snRNA gene expression by differential transcription. AB - The expression of mouse embryonic U1 snRNA (mU1b) genes is subject to stage- and tissue-specific control, being restricted to early embryos and adult tissues that contain a high proportion of stem cells capable of further differentiation. To determine the mechanism of this control we have sought to distinguish between differential RNA stability and regulation of U1 gene promoter activity in several cell types. We demonstrate here that mU1b RNA can accumulate to high levels in permanently transfected mouse 3T3 and C127 fibroblast cells which normally do not express the endogenous U1b genes, and apparently can do so without significantly interfering with cell growth. Expression of transfected chimeric U1 genes in such cells is much more efficient when their promoters are derived from a constitutively expressed mU1a gene rather than from an mU1b gene. In transgenic mice, introduced U1 transgenes with an mU1b 5' flanking region are subject to normal tissue-specific control, indicating that U1b promoter activity is restricted to tissues that normally express U1b genes. Inactivation of the embryonic genes during normal differentiation is not associated with methylation of upstream CpG-rich sequences; however, in NIH 3T3 fibroblasts, the 5' flanking regions of endogenous mU1b genes are completely methylated, indicating that DNA methylation serves to imprint the inactive state of the mU1b genes in cultured cells. Based on these results, we propose that the developmental control of U1b gene expression is due to differential activity of mU1a and mU1b promoters rather than to differential stability of U1a and U1b RNAs. PMID- 1508719 TI - Oligodeoxynucleotide-directed photo-induced cross-linking of HIV proviral DNA via triple-helix formation. AB - The HIV proviral genome contains two copies of a 16 bp homopurine.homopyrimidine sequence which overlaps the recognition and cleavage site of the Dra I restriction enzyme. Psoralen was attached to the 16-mer homopyrimidine oligonucleotide, d5'(TTTTCT-TTTCCCCCCT)3', which forms a triple helix with this HIV proviral sequence. Two plasmids, containing part of the HIV proviral DNA, with either one (pLTR) or two (pBT1) copies of the 16-bp homopurine.homopyrimidine sequence and either 4 or 14 Dra I cleavage sites, respectively, were used as substrates for the psoralen-oligonucleotide conjugate. Following UV irradiation the two strands of the DNA targeted sequence were cross linked at the triplex-duplex junction. The psoralen-oligonucleotide conjugate selectively inhibited Dra I enzymatic cleavage at sites overlapping the two triple helix-forming sequences. A secondary triplex-forming site of 8 contiguous base pairs was observed on the pBT1 plasmid when binding of the 16 base-long oligonucleotide was allowed to take place at high oligonucleotide concentrations. Replacement of a stretch of six cytosines in the 16-mer oligomer by a stretch of six guanines increased binding to the primary sites and abolished binding to the secondary site under physiological conditions. These results demonstrate that oligonucleotides can be designed to selectively recognize and modify specific sequences in HIV proviral DNA. PMID- 1508718 TI - Splicing signals in Drosophila: intron size, information content, and consensus sequences. AB - A database of 209 Drosophila introns was extracted from Genbank (release number 64.0) and examined by a number of methods in order to characterize features that might serve as signals for messenger RNA splicing. A tight distribution of sizes was observed: while the smallest introns in the database are 51 nucleotides, more than half are less than 80 nucleotides in length, and most of these have lengths in the range of 59-67 nucleotides. Drosophila splice sites found in large and small introns differ in only minor ways from each other and from those found in vertebrate introns. However, larger introns have greater pyrimidine-richness in the region between 11 and 21 nucleotides upstream of 3' splice sites. The Drosophila branchpoint consensus matrix resembles C T A A T (in which branch formation occurs at the underlined A), and differs from the corresponding mammalian signal in the absence of G at the position immediately preceding the branchpoint. The distribution of occurrences of this sequence suggests a minimum distance between 5' splice sites and branchpoints of about 38 nucleotides, and a minimum distance between 3' splice sites and branchpoints of 15 nucleotides. The methods we have used detect no information in exon sequences other than in the few nucleotides immediately adjacent to the splice sites. However, Drosophila resembles many other species in that there is a discontinuity in A + T content between exons and introns, which are A + T rich. PMID- 1508720 TI - Interaction of N-terminal domain of U1A protein with an RNA stem/loop. AB - The U1A protein is a sequence-specific RNA binding protein found in the U1 snRNP particle where it binds to stem/loop II of U1 snRNA. U1A contains two 'RNP' or 'RRM' (RNA Recognition Motif) domains, which are common to many RNA-binding proteins. The N-terminal RRM has been shown to bind specifically to the U1 RNA stem/loop, while the RNA target of the C-terminal domain is unknown. Here, we describe experiments using a 102 amino acid N-terminal RRM of U1A (102A) and a 25 nucleotide RNA stem/loop to measure the binding constants and thermodynamic parameters of this RNA:protein complex. Using nitrocellulose filter binding, we measure a dissociation constant KD = 2 x 10(-11) M in 250 mM NaCl, 2 mM MgC2, and 10 mM sodium cacodylate, pH 6 at room temperature, and a half-life for the complex of 5 minutes. The free energy of association (delta G degrees) of this complex is about -14 kcal/mol in these conditions. Determination of the salt dependence of the binding suggests that at least 8 ion-pairs are formed upon complex formation. A mutation in the RNA loop sequence reduces the affinity 10 x, or about 10% of the total free energy. PMID- 1508721 TI - Characterization of antibodies against methyl-pppN cap structure: plant U3 small nucleolar RNA is recognized by these antibodies. AB - In eukaryotes, many small nuclear RNAs contain either a trimethylguanosine cap structure of a gamma-monomethyl (me) cap structure. Previously, we reported the characterization of anti-mepppG antibodies which recognize methyl-capped RNAs with G as the initiation nucleotide. We report here the preparation of antibodies against mepppN cap structure. Anti-mepppN antibodies recognized only mepppN from a mixture of mepppN and pppN and immunoprecipitated mepppA-capped U3 small nucleolar RNA from a mixture of cowpea cell RNAs. These anti-mepppN antibodies recognized methylated nucleoside triphosphates (mepppA, mepppC, mepppG and mepppU) with nearly equal efficiency; however, these antibodies did not recognize methyl phosphate or methylated mononucleotides. These antibodies will be useful in the identification and characterization of all methyl-capped RNAs no matter which is the initiation nucleotide. PMID- 1508722 TI - Multiple octamer binding sites in the promoter region of the bovine alpha s2 casein gene. AB - Using a set of overlapping oligonucleotides from the promoter region of the bovine alpha s2-casein gene we have identified two nuclear factors which probably are involved in expression of this gene and the related calcium sensitive alpha s1- and beta-casein genes. One of these factors which was present in extracts of all tissues that have been tested including Hela cells turned out to be the octamer binding protein OCT-1. Oct-1 binds with different affinity to 4 sites at positions centred around -480, -260, -210 and -50. The strongest of these 4 binding sites, the one around position -50, is highly conserved in all calcium sensitive caseins of mouse, rat, rabbit and cattle. The other nuclear factor (MGF, mammary gland factor) which is specifically expressed in the mammary gland, binds to a site around position -90. This binding site is also highly conserved in all calcium sensitive caseins of mouse, rat, rabbit and cattle. PMID- 1508724 TI - An assessment of neural network and statistical approaches for prediction of E. coli promoter sites. AB - We have constructed a perceptron type neural network for E. coli promoter prediction and improved its ability to generalize with a new technique for selecting the sequence features shown during training. We have also reconstructed five previous prediction methods and compared the effectiveness of those methods and our neural network. Surprisingly, the simple statistical method of Mulligan et al. performed the best amongst the previous methods. Our neural network was comparable to Mulligan's method when false positives were kept low and better than Mulligan's method when false negatives were kept low. We also showed the correlation between the prediction rates of neural networks achieved by previous researchers and the information content of their data sets. PMID- 1508723 TI - Cloning of the gene for the 73 kD subunit of the DNA polymerase alpha primase of Drosophila melanogaster. AB - We have isolated both cDNA and genomic clones for the 73 kDa subunit of the DNA polymerase alpha primase of Drosophila melanogaster. Analysis of these clones has identified an open reading frame of 1959 bases coding for a protein of 72.5 kDa. Northern analysis has shown the mRNA for the gene to be approximately 2.5 kb, and comparison of the cDNA and the genomic clones shows that the coding region of the gene lacks introns. The 5' end of the transcript has been mapped by primer extension, and the position of the gene in the genome mapped using in situ analysis. Computer analysis has been carried out on both coding and non coding regions of the gene. The protein sequence shows some homology to the analogous subunit in the S. cerevisiae DNA polymerase alpha, however a search of the data banks failed to reveal other homologies, or provide any clues as to the function of the protein. Analysis of the non-coding regions indicates some potential control regions for the gene. The 73 kDa protein has been overproduced, but a preliminary analysis failed to reveal any enzymatic activities. PMID- 1508725 TI - RecA protein promotes rapid RNA-DNA hybridization in heterogeneous RNA mixtures. AB - The nucleoprotein filament formed by the RecA protein of Escherichia coli on single-stranded DNA catalyzes the hybridization of RNA transcripts with single stranded DNA sequences at 37 degrees C, in vitro. RecA protein rapidly promotes hybridization, even when noncomplementary RNA is in a millionfold nucleotide excess over hybridizing RNA, and in a thousandfold nucleotide excess over hybridizing single-stranded DNA. Heterologous double-stranded DNA and RecA-coated noncomplementary single-stranded DNA are also poor competitors of RNA transcripts produced in vitro. Since large excesses of noncomplementary RNA fail to inhibit sharply the hybridization reaction by RecA protein under mild, non-degradative conditions, the reaction may be useful in the identification and isolation of transcripts produced in vivo. PMID- 1508726 TI - Structural conservation of putative functional motifs between Xenopus and human TFIIE-beta. PMID- 1508727 TI - Characterization of restriction endonuclease activities in tetracycline producing strains of Streptomyces aureofaciens. PMID- 1508728 TI - Optimization of the signal-to-noise ratio in south-western assays by using lipid free BSA as blocking reagent. PMID- 1508729 TI - High efficiency gene transfer into mammalian cells by a double transfection protocol. PMID- 1508730 TI - Directional cloning of PCR products using exonuclease III. PMID- 1508731 TI - Minimizing deletion mutagenesis artifact during Taq DNA polymerase PCR by E. coli SSB. PMID- 1508732 TI - Cloning of Hepadnaviruses using microquantity serum. PMID- 1508734 TI - Pathophysiology of lung cancer. AB - Cigarette smoking is responsible for approximately 30% of all cancer deaths. Smoking accounts for 85% of lung cancer cases in men and 75% in women. There are about 38 million former cigarette smokers and about 50 million smokers in the United States today. Smoking rates are higher among blacks, blue collar workers, and less educated people. More than 140,000 lives will be lost to cancer each year because of tobacco smoking. All cancers caused by cigarette smoking could be prevented. It is hoped that public education, smoking cessation programs, and efforts to eliminate carcinogens in the work environment will impact the future incidence of new lung cancer cases. As preventive measures continue, refinement in the diagnosis and treatment of cancer must continue to advance. The recognition of any one of cancer's seven warning signals and prompt subsequent action could lead to earlier detection and a chance for 3- and 5-year survival rates to improve. With medical and research progress, clinical concerns have grown beyond addressing only the patient's physical needs to include important issues such as employment and insurance needs and the psychosocial needs of both the patient and the family as they learn to live with cancer. PMID- 1508735 TI - Diagnostic testing for patients with lung cancer. AB - Lung cancer is the most common cause of cancer death for men and women in the United States. The diagnosis of lung cancer is cause for fear and anxiety in the general population because more than 85% of people with lung cancer are dead within 5 years. A diagnosis of lung cancer begins with a thorough health assessment followed by appropriate diagnostic testing. The nurse has the greatest amount of interaction with the patient and can help to facilitate the diagnostic process in a manner that renders it less stressful and effective. The nursing process of assessment, diagnosis, planning, goal setting, and evaluation guides the prepared nurse in accomplishing this task. PMID- 1508733 TI - New nucleotide sequence data on the EMBL File Server. PMID- 1508736 TI - Smoking. AB - Cigarette smoking remains a major health problem in not only the United States but the world. The dependency-producing effects of nicotine are well documented. Primary prevention, preventing the initiation of smoking, is receiving increased attention in the field of health education. Secondary prevention, smoking cessation, is showing promising results. Perhaps the goal of a smoke-free America by 2000 is not a "pipe dream" after all. PMID- 1508737 TI - Trends in radiation therapy for the treatment of lung cancer. AB - Two methods of radiotherapy delivery, external beam radiotherapy and brachytherapy, are important curative and palliative modalities for treating lung cancer. In situations when cure is not possible, radiotherapy may be effective in controlling lung cancer cell growth. Investigative use of other ways of delivering radiation therapy, CHART, intraoperative radiotherapy, remote afterloading brachytherapy, and hyperthermia, are currently under way. Nursing diagnoses and care are based on assisting the patient in understanding the rationale for receiving radiation therapy, the way in which radiation therapy is administered, and its potential side effects. PMID- 1508738 TI - Surgical resection of lung cancer. AB - Surgery remains the treatment of choice for patients with lung cancer who demonstrate resectable tumors. The type of surgical procedure performed depends on the degree of metastasis and the functional lung capacity of the patient. In addition to problems common to all surgical patients, complications such as cardiac arrhythmias, pulmonary embolus, respiratory failure, bronchopleural fistula, and empyema may occur. Although survival statistics for patients with lung cancer remain poor, the common denominator in patients that have survived 5 years is surgical resection. PMID- 1508739 TI - Psychosocial implications of lung cancer. AB - Patients with lung cancer who are encouraged and permitted to verbalize their feelings by a staff that is interested, empathetic, and nonjudgmental are better able to overcome feelings of anxiety and fear, and they progress through the stages of the grieving process more easily. Communications between the lung cancer patient and the multidisciplinary staff should occur freely and without restraint. Unrealistic expectations made of the patient who is struggling to cope will almost certainly increase anxiety. Interventions must address coping responses of the patient and family living with lung cancer. Caregivers working with patients whose diagnoses are not favorable must examine their own feelings regarding terminal disease states and death before the entire cancer experience can be discussed openly and comfortably by the patient, family members, and health care team. The focus of care for families and patients living with lung cancer should be on care rather than cure. PMID- 1508740 TI - Nursing care of the terminal lung cancer patient. AB - Care of the terminal lung cancer patient will be more effective when a multidisciplinary approach is used. Planning for terminal care should not be delayed until the last few hours or days of life. Hospice care offers the terminal lung cancer patient an alternative to dying in a hospital or nursing home. Caring support to alleviate pain and prevent suffering is the goal of nursing care for the terminal cancer patient. Nursing interventions should be directed toward allowing the patient to retain decision-making authority in care for as long as possible. PMID- 1508741 TI - Vision and vision loss. AB - To provide supportive and effective care to people who must adapt to blindness or visual impairment, nurses and other health care professionals have a responsibility to be knowledgeable about the unique effect of ophthalmic disorders on the body, spirit, and mind. It is also evident that nurses must clearly understand their own emotions and social reactions to blindness and visual loss so that they can more clearly assist their clients through adaptation. PMID- 1508742 TI - Knowledge deficit in the ophthalmic surgical patient. AB - This case history illustrates some important aspects of the informational needs of ophthalmic surgery patients. As is true with many ophthalmic patients, this patient had a relatively high level of anxiety regarding his potential loss of vision postoperatively. This concern is magnified in a monocular patient. The nurse must help these patients put this concern in the proper perspective by providing accurate information. The nurse who performs such extensive preoperative teaching takes on a role that entails a great deal of responsibility. A planned program of information with written objectives and an outline of the important information to include will help the nurse provide a high level of care in meeting the knowledge needs of the patient. It is not necessary, or even desirable, to develop a plan for each individual patient. A written outline of important and necessary information for each type of ophthalmic surgical procedure provides a means of assuring that the teaching plan is complete and accurate. The information in the teaching plan should be validated by other physician and nurse colleagues. A written plan can save time once it is developed, because the nurse can follow the standard plan, modifying the presentation to meet each patient's specific needs as necessary. The patient indicated feeling somewhat overwhelmed with information when faced with his ophthalmic surgery. It is very important to ensure that the patient and appropriate significant others get both verbal and written information in these situations. The written information gives the patient and his or her family a reference to use when they return home and begin to assimilate more of the information given to them by the nurse. The patient in this case history and his wife both referred to the written instructions several times before and after the operation to verify certain information. The written materials presented information at an appropriate reading level and had large well-spaced print. Repetition (whether verbal or in written format) is important because it reinforces important aspects of the necessary information. The nurse at the surgical facility repeated the postoperative requirements to the patient and his wife before they left the center and made sure that they had the written instructions as well. The nurse demonstrated the necessary motor skills and gave the patient and his wife the opportunity to return the demonstration. PMID- 1508743 TI - Nursing care of the cataract patient: today's outpatient approach. AB - Total cataract patient care encompasses nursing assessment, clinical management, emotional support, and the accessibility of the nurse to the patient. Because ophthalmic nurses develop a close relationship with the cataract patient, they are often the first health care professional the patient calls for advice. Patient education and adequate time to listen and respond are integral components in an outpatient cataract surgical approach. All aspects of the nursing care of the cataract patient provide challenge and satisfaction as the ophthalmic registered nurse experiences surgery with the patient and supervises the return to improved vision and quality of life. The nurse must always remember that there is a whole person attached to the eye. Although ophthalmic nursing is specialized and highly technical, patience, empathy, and encouragement are essential in the care of the patient before, during, and after cataract surgery. PMID- 1508744 TI - Diabetic retinopathy. AB - The risk of blindness is 25 times greater in diabetics than nondiabetics. Medical, laser, and surgical interventions have the potential to enhance greatly the prognosis of maintaining useful vision throughout life. Patient education is paramount to improve comprehension of the condition, recommended treatment modalities, and compliance with prescribed regimens. Nursing assessments and interventions related to anxiety, discomfort, ineffective coping mechanisms, and immobility add a quality link in the multidisciplinary approach surrounding the delivery of care to patients with diabetic retinopathies. PMID- 1508745 TI - Macular degeneration. AB - With the "graying of America," the patient population at risk for developing ARMD will continue to grow. As researchers continue to study the cause, pathologic changes, and risk factors associated with the development of this disease, preventive measures and improved treatment options will become available. The education of ARMD patients in the recognition of signs of the disease for early treatment, treatment options, and the availability of resources is essential for the nurse caring for this population. Adjustment to visual loss will be an ongoing process, during which the nurse can be a source of support, guidance, and encouragement, as patients assimilate newly acquired behaviors and roles into their self-image. PMID- 1508746 TI - Choroidal melanoma. AB - Choroidal melanoma is a rare and deadly cancer. Nursing care for these patients involves ophthalmic clinical expertise as well as psychosocial and emotional support. Although past research has been helpful in determining the prognosis of these patients, it is impossible to predict with certainty which patients have tumors or nevi that will grow, will compromise their vision, or will kill them. Providing emotional support, establishing a good rapport with the patients and their support persons, and encouraging patients to schedule and adhere to their mutually agreed on follow-up appointments are nursing interventions that may save or prolong a patient's life. PMID- 1508747 TI - Worldwide blindness. AB - Blindness affects approximately 42 to 52 million people worldwide. This article examines the major causes of blindness, including cataract, trachoma, glaucoma, onchocerciasis, nutritional deficiencies, and ocular trauma. Numerous case studies supplement the text. PMID- 1508748 TI - [Iatrogenic damage in neonatology]. PMID- 1508749 TI - [Celiac disease and autoimmunity]. AB - Immune mechanisms have been invoked to explain coeliac disease and associations between this and other immunologically mediated diseases have been described. A direct relationship proposed is that coeliac disease may be associated with a range of autoimmune disease through the formation of immune complexes in the small intestine. It's more probable a common origin in an inherited predisposition to hypersensitive immuno responses to extrinsic antigens or auto antigens. The association between coeliac disease and particular histocompatibility antigens was recognised. PMID- 1508751 TI - [The microbiological exam of the urine: what significance in urinary tract infections?]. AB - 11,829 urine cultures, coming from the Pediatrics Department of Florence and other hospital divisions for adults in the period 1st of July-31st of December 1990, have been examined in the Bacteriology and Virology Laboratory of the University Hospital of Florence. Besides illustrating various methods of drawing, preservation and transport of the urinary specimen, the authors showed the incidence of bacterial species responsible of urinary tract infections (U.T.I.). E. coli was showed to be the most frequently isolated bacterial strain, followed by Streptococcus faecalis and Proteus indole negative. The incidence of fimbriated E. coli infections was studied in pediatric and adult patients with urinary tract infections; a higher isolation frequency of fimbriated E. coli was showed in pediatric patients and in these patients the correlation was studied between the presence of fimbriated E. coli and the severity of infection (pyelonephritis, recurrent U.T.I.). The percentages of resistance of the isolated strains against the most common chemotherapies was also showed, studying their variations, for some chemotherapies, during about twenty years. PMID- 1508750 TI - [The follow-up of malformation uropathies diagnosed "in utero"]. AB - Prenatal diagnosis and postnatal follow-up of urinary tract congenital malformations are discussed. Among 9501 overall births, 25 newborns with urinary tract congenital malformations were born (2.6 x 1,000). Twenty cases had been diagnosed "in utero" by ultrasound scan (4 cases of Potter sequence, 2 cases of prune-belly anomaly, 3 cases of polymalformed infants with urinary involvement, 10 cases of hydronephrosis, 1 case of ectopic kidney). In 8 newborns a surgical treatment was successfully performed. Eight newborns died and in other 4 cases clinical and ultrasonographic are not yet fulfilled. In 2 cases the prenatal diagnosis of urinary tract malformations was not confirmed by the postnatal evaluation. Our experience shows that the prenatal diagnosis of congenital malformations of urinary tract is particularly useful, even considering the opportunities of perinatal management and postnatal surgical treatment in several cases. PMID- 1508752 TI - [The use of the computer in the neonatal intensive therapy unit: the current and prospective aspects]. AB - The Authors assert that computer can give an adjunctive value to our abilities, improve the punctuality of own service, lighten the duties of routine (leaving free time for own-self or for adjournment). We have noticed a gradual but continuous increase of the use of the computer in the last years in hospital particularly in the Neonatology department and in the NICU, even because in these departments the data to compare are numerous. In the Brindisi's NICU since 1/7/1986 there has been a process of progressive increase of the use of the computer, based on three directions: filing data of the patients, computer assisted management of the treatment of RDS, computer-assisted follow-up of the risk-baby, and management of the resources. Moreover are reported possibilities of future applications, as records of diagnosis and helped therapy, interface with medical equipment, linking with databank and with the hospital's mainframe. PMID- 1508753 TI - [Abdominal migraine simulating acute abdomen]. AB - Migraine is a variant of headache often associated with neurologic and/or vegetative symptoms mainly represented by abdominal pain. This symptom may occur some hours before migraine manifestation and in these cases the differential diagnosis with other clinical conditions characterized by abdominal pain, which is very common during childhood, may be difficult. Abdominal migraine can be diagnosed only if a close relationship is demonstrated between the abdominal symptoms and migraine. Alteration of consciousness is a well known feature during migraine and in some cases EEG may show SNC involvement during the attack. We report a case of abdominal migraine attack evaluated by EEG. The patient, a 10 years old male, presented with a picture of acute abdomen. An EEG performed at the occurrence of the early headache symptoms and of consciousness alteration demonstrated a pattern characterized by a lowering in the electric activity on the left hemisphere. Some hours later he developed a clear migraine followed by disappearance of the abdominal symptoms. This observation confirms the possible association of migraine with a picture simulating an acute abdomen and suggests that the differential diagnosis with a true surgical condition may be achieved by the observation of the progression of symptoms and by early evaluation of patient with EEG. PMID- 1508754 TI - [Otitis media in childhood: a critical review of the literature]. AB - Infection of the middle ear is one of the most common childhood illnesses accounting for one-third of the pediatrics practice during the first five years of life. Therefore treatment and prevention of the otitis media are of considerable importance. A review of the literature of the otitis media during the pediatric age is reported. In fact in the last years a large amount of knowledge, sometimes referring discordant opinions, has been acquired. The Authors report epidemiology, anatomy, pathology, physiology, microbiology, classification, clinical data diagnosis and therapy of the otitis media. Common conditions of the middle ear (normal, acute otitis media, chronic otitis media, recurrent otitis media) are described. In particular acute otitis media, otitis media with effusion, perforation of the tympanic membrane, fluid level in the middle ear, severe retraction or bulging of the tympanic membrane are pointed out in color-photographs. PMID- 1508755 TI - [The catarrhal child]. AB - The first seven years of a child's development are often described as the catarrhal stage. This is because of the increased incidence of upper respiratory tract infections. Nasal obstruction in the children is common and symptoms are often distressing. The authors report a rational approach to this problem to produce effective treatment of recurrent nasal obstruction. In particular clinical features, diagnosis, and therapy of recurrent rhinitis, adenoid hypertrophy, and tonsillar obstruction are described. The indications for adenoidectomy, tonsillectomy or adenotonsillectomy has been questioned. PMID- 1508756 TI - [An epidemiological study of skin tuberculin positivity in the province of La Spezia in 1988-1991: an evaluation of the results in 3932 cases]. AB - In recent years (1989-1991) the author has tested for positivity of tuberculosis (with Tine-Test) 3.932 children, belonging to two age groups: 1-3 and 10-11 years. The results of positivity to the cutireaction (0% and 0.32% respectively) were lower, in comparison to other published reports. PMID- 1508757 TI - [Pulmonary hemosiderosis induced by cow's milk proteins: a discussion of a clinical case]. AB - Pulmonary hemosiderosis (PH), a rare pathology, usually occurring during infancy and childhood, is characterized by numerous and repeated intra-alveolar bleedings, interstitial iron build-up with consequent progressive fibrosis and severe anemia. PH can be basically divided into 3 different categories: Primitive or idiopathic, involving a primitive deficit of antioxidizing enzymes in the erythrocytes in genetically predisposed subjects; Secondary, subsequent to chronic pneumopathy or cardiopathy; Associated with various pathologies including collagenopathies, glomerulonephritis, myocardiopathies, diabetes, steatorrhea, tireotossicosis. A particular type of Pulmonary Hemosiderosis, associated with allergy to cow's milk, has been described for the first time by Heiner. We present in this paper our personal experience of a young patient suffering from pulmonary hemosiderosis induced by cow's milk protein. PMID- 1508758 TI - [The Schonlein-Henoch syndrome with testicular involvement: a report of 4 cases]. AB - The authors report about four children with Schonlein-Henoch purpura in whom the clinical picture has been characterized by an unusual localization, the testicular involvement. The main clinical aspects of this feature are illustrated and the approach to its diagnosis and its management is discussed. PMID- 1508759 TI - [Dysplasia epiphysealis capitis femoris (Meyer's disease). An emergent pathology from the echographic screening of congenital hip dysplasia]. AB - The authors present a case of Meyer disease. The knowledge of this pathology, emerging from the ultrasonic screening of the hip, is useful to the pediatrician in the differential diagnostic argument. PMID- 1508761 TI - [The Silver-Russel syndrome]. AB - The authors report a case of Silver-Russel syndrome with severe deficit growth observed since intrauterine life. They describe the major features, that are constant and the minor features, that are variable and numerous. The features not always are present at birth. The A. exclude in this case a genetic cause and suggest a possible motherly cause. PMID- 1508760 TI - [Fukuyama-type congenital muscular dystrophy with the presence of ocular anomalies]. AB - The authors report a case with Fukuyama type congenital muscular dystrophy (FCMD) and severe ocular abnormalities. Muscular dystrophy was confirmed by EMG, high muscle enzyme value and muscular biopsy. Computed tomography (CT) of the brain at 15 months of life showed mild central and cortical atrophy. Repeated CT scans at 22 and 32 months showed progressive character of the atrophy, with preservation of the cerebellar areas and the central grey matter only. Ophthalmologist examination revealed nystagmus, severe visual deficit, optic nerve atrophy and irregular color of the retina, especially in the peripheric areas. Electroretinography (ERG) was normal, cortically evoked visual responses (PEV) were absent. The association of congenital muscular dystrophy with brain changes and ocular abnormalities were found in FCMD, muscle-eye-brain disease (MEB) and Walker-Walburg syndrome (WWS). Our report, according to the recent literature, suggests that ocular lesions are caused by the same mechanism that provokes the central nervous system anomalies. It is probably of genetic origin: FCMD, MEB and WWS could be development abnormalities with a continual spectrum of disease severity. PMID- 1508763 TI - Be more precise. PMID- 1508764 TI - The relationship between orthopedics and industry revisited: ethical guidelines. PMID- 1508762 TI - [Early autism and congenital muscular dystrophy: a clinical case]. AB - The authors describe the case of a twelve-year-old patient presenting early autism associated with congenital muscular dystrophy--subtype IV, according to the subclassification of Fukuyama (slight mental retardation, ability to walk, muscle pseudohypertrophy). To our knowledge, this association has never been reported. Several factors may have played a causative role in the development of an autistic disorder in the patient. The authors suggest the following as the most significant ones: disharmonious personality, weak emotional structure, inadequate primary relation with the mother, poor environmental influences, frustrations encountered because of the muscular disorder. PMID- 1508765 TI - Separation of tendon ends after Achilles tendon repair: a prospective, randomized, multicenter study. AB - Fifty-seven patients treated for an acute rupture of the Achilles tendon were studied. The patients were randomized into a Mason suture technique or a reinforced continuous six-strand suture technique, and markers were attached to each tendon end perioperatively. The postoperative separation of the markers was studied by repeat radiographic examination. Despite immobilization, separation developed after a biphasic course, and after 7 weeks the mean separation was 10.5 mm. No difference was found between the two techniques. We attempt to correlate the separation to the clinical outcome, examined at 1 year follow up. PMID- 1508766 TI - Immediate plate fixation of highly comminuted femoral diaphyseal fractures in blunt polytrauma patients. AB - From January 1982 through December 1988, 150 patients with 153 Winquist Class III and IV comminuted diaphyseal femur fractures due to high energy blunt trauma were treated with immediate plate fixation. A total of 260 major general surgical systems were injured in 150 patients. Forty-nine patients did not have adequate preoperative spine radiographs due to positioning or time factors. Nineteen patients had spine fractures; nine were diagnosed post-femoral fixation. The average injury severity score (ISS) was 22.7. Three patients died (2%). Our institution predicted mortality with this ISS for patients without pelvic or femur fractures at 15% (P = .0003). Six patients moved to other states and three were lost to follow up due to noncompliance. One of us reviewed 141 fractures in 138 patients at a minimum of 12 months follow up and completion of treatment. Forty-nine fractures were open; 8 grade I, 25 grade II, 10 grade IIIA, 4 IIIB, 2 IIIC. A total of 153 pelvic or ipsilateral major orthopedic injuries were present in 141 fractures. An additional 188 major associated orthopedic injuries were noted. The average time to union was 17.2 weeks. One plate was applied in 11 degrees of varus. Five plates failed from fatigue and five from repeat traumas. Seven plate failures were rodded and healed within 8 weeks. There was one persistent nonunion. One fracture, open IIIC, became infected after uniting. One patient has 110 degrees of knee motion and 140 fractures have greater than 130 degrees of knee motion. Plate fixation is a safe technique for immediate femoral stabilization in the face of high energy blunt trauma. Failures occur late and are easy to reconstruct. Intramedullary nails are the preferred method of reconstruction. Ultimate knee function is excellent. Infection rates (1/49) in open fractures are acceptably low. PMID- 1508767 TI - Surgical results in anterior cervical discectomy and fusion using a countersunk interlocking autogenous iliac bone graft. AB - The purpose of this study was to evaluate the surgical results of anterior cervical discectomy and fusion using a countersunk interlocking autogenous iliac bone graft. Two hundred thirty-two patients were followed for an average of 6.8 years. All patients suffered neck and arm pain. Two hundred twenty patients received conservative treatment for at least six months. Overall results were satisfactory in 202 patients (87%) and unsatisfactory in 30 patients (13%). The pseudoarthrosis rate was 6.5% which is significantly lower than previous reports. The premise of this technique is that the interlocking graft prevents migration, promotes fusion by providing immobilization, and restores the height of the interspace. Anterior cervical discectomy and fusion, using a countersunk interlocking autogenous iliac bone graft, is a satisfactory surgical procedure in which successful pain relief is to be expected. PMID- 1508768 TI - Scaphoid fractures: assessment and treatment. AB - The scaphoid is the most commonly fractured carpal bone. The fracture pattern and its relationship to the blood supply have significant implications regarding treatment and prognosis. Prompt recognition and treatment are fundamental to successful management. PMID- 1508769 TI - Arthroscopic lysis of adhesions after New Jersey LCS total knee arthroplasty. PMID- 1508770 TI - The diagnosis and treatment of fractures of the occipital condyle. PMID- 1508771 TI - Intrauterine femur fracture. PMID- 1508772 TI - Adamantinoma of the tibia. PMID- 1508773 TI - Avascular necrosis after fracture-separation of the distal end of the humerus in children. AB - Fracture-separation of the distal end of the humerus in children has been reported infrequently, and may be misdiagnosed as a fracture of the condyle or a traumatic dislocation of the elbow. We discuss eight cases of a seldom reported complication following fracture-separation of the distal end of the humerus. This complication consists of dissolution of the trochlea within three to six weeks postinjury and a defect of the medial or central part of the condyle that develops later. The fractures were severely displaced fracture-separation of the distal end of the humerus with large medial or lateral metaphyseal fragment, but initially misdiagnosed as a fracture of the medial, lateral condyle or a traumatic dislocation of the elbow in six of eight cases. We performed open reduction in six cases because of initial misdiagnosis or because of difficulty in satisfactory closed reduction. We speculated that this complication is due to avascular necrosis of the distal end of the humerus, and that fracture-separation of the distal end of the humerus is more common than reported. PMID- 1508774 TI - Rehabilitation after ACL reconstruction: function testing. PMID- 1508775 TI - Radiologic case study. Congenital syphilis. PMID- 1508776 TI - Answer please. Simple (unicameral) bone cysts. PMID- 1508777 TI - [Retinoic acid regulates the processes of growth and differentiation]. PMID- 1508778 TI - [Modification of the processes of chemical mutagenesis and carcinogenesis by synthetic phenol antioxidants such as butylated hydroxyanisole]. PMID- 1508779 TI - Acute headache. Differential diagnosis and management of the three types. AB - Headache is a common complaint with many potential causes. Each patient should be thoroughly examined to identify the condition producing the headache. Appropriate treatment varies according to headache type, so therapy should not be initiated until the diagnosis has been established. Dr Diamond reviews the differential diagnosis of headache and techniques for managing its various forms. PMID- 1508780 TI - Sports injuries. Practical diagnostic and management concerns for primary care physicians. AB - Both recreational and elite athletes often sustain musculoskeletal injuries. Common problems--muscle cramps, burners (or stingers), and ankle and shoulder injuries--can be managed effectively with certain basic techniques. Initial measures are particularly important in facilitating the injured athlete's rapid return to activity. PMID- 1508781 TI - Emergency management of acute pain. New options and strategies. AB - Emergency physicians often encounter patients in pain and may also have to cope with other problems (eg, alcohol intoxication, a patient's stubborn will to drive after the emergency department visit, narcotic "allergy"). Novel approaches can be used to treat these patients. Dr Heller discusses such approaches, including measures for treating patients with drug-seeking behavior (eg, use of nonnarcotic parenteral agents), and describes treatment options for patients with such specific conditions as hypotension, chest pain, and renal colic. PMID- 1508782 TI - Acute pain in the elderly. AB - Acute-pain syndromes are common in the elderly. They often occur in association with the degenerative diseases that are likely to affect this age-group. Diagnosis of the specific type of acute pain is made difficult by several factors, including atypical presentation and underreporting. Treatment can be complicated by the polypharmacy that is prevalent among older adults and by age related physiologic changes. Effective management requires knowledge of the effects of various pharmacologic agents in older adults and of the health and psychosocial status of the individual patient. PMID- 1508783 TI - Acute and postoperative pain. Management from a primary care perspective. AB - Most pain is controllable. Patient education and careful intraoperative technique are useful prophylactic measures. Simple analgesics and non-steroidal anti inflammatory drugs reduce pain, fever, and inflammation and are well tolerated when dosing guidelines are followed carefully. In patients whose pain is not controlled with these measures, the addition of a weak narcotic analgesic is reasonable. If relief is still inadequate, a stronger narcotic alone or in combination with another analgesic may be needed. The advent of patient controlled analgesia has diminished some of the objections to continuous intravenous infusion of narcotics. Various acute-pain syndromes respond to blockade of the sympathetic or somatic neural pathways. Knowledge of the appropriate anatomic structures and careful technique are mandatory with this method. Moreover, it should be considered only one part of a comprehensive treatment plan. PMID- 1508784 TI - Orofacial and craniofacial pain. Primary care concerns. AB - A patient who experiences an acute episode of oral or facial pain is likely to consult a primary care physician. Dr Green reviews the basic information needed to distinguish among the more common types and causes of such pain. Once the pain's source is determined, treatment can be prescribed or an appropriate referral made. PMID- 1508785 TI - In human monocytes IL-1 stimulates a phospholipase C active on phosphatidylcholine and inactive on phosphatidylinositol. PMID- 1508786 TI - Synthesis of leukotrienes and its pharmacological control in the rabbit heart. PMID- 1508787 TI - Differential pattern of expression of G proteins in nucleus striatum from 6 hydroxydopamine lesioned rats. PMID- 1508789 TI - Chronic morphine treatment increases G proteins alpha subunits mRNAs in discrete regions of rat brain. PMID- 1508788 TI - G-proteins and diabetic encephalopathy: molecular mechanisms underlying the functional alterations. PMID- 1508790 TI - High performance liquid chromatographic separation with electrochemical detection of amino acids focusing on neurochemical application. PMID- 1508791 TI - Tenotomy does not affect CGRP expression at the rat neuromuscular junction. PMID- 1508792 TI - Down regulation of muscarinic receptor subtypes messenger RNA in rat primary culture of corticostriatal neurons. PMID- 1508794 TI - Neurotoxins affecting cognitive functions reduce B-50 phosphorylation in rat brain. PMID- 1508793 TI - On the molecular site of action of defibrotide. PMID- 1508795 TI - Glucocorticoid-induced thymocyte apoptosis: inhibition by interleukin-2 and interleukin-4. PMID- 1508796 TI - The antiproliferative effect of suramin on the cancer cell line SW-13 is mediated by the inhibition of transforming growth factor beta 1 (TGF-beta 1). PMID- 1508797 TI - A common distribution of the semicarbazide-sensitive amine oxidase activity (SSAO) in white adipose tissue (WAT). PMID- 1508798 TI - Endothelin-1 increases intracellular calcium content in bovine parathyroid endothelial cells. PMID- 1508799 TI - Production and release of eicosanoids from rat hypothalamic explants in vitro. PMID- 1508800 TI - Effects of bacterial endotoxin, interleukin-1 and prostaglandins on thermoregulation and cerebrospinal fluid-calcium concentration in rabbits. PMID- 1508801 TI - Influence of paired pulse inhibition on hypoxia-induced changes in hippocampal CA1 field potentials. PMID- 1508802 TI - A1-mediated adenosine control and ATP P2Y site involvement in protein kinase C activity and purine release from cultured astrocytes. PMID- 1508803 TI - Distribution of topically administered drugs to the posterior segment of rabbit eye. PMID- 1508804 TI - Ofloxacin concentrations in human inflamed pericoronal tissue after oral administration. PMID- 1508805 TI - Differential effect of aging on albumin and plasma protein binding of diazepam and salicylic acid in healthy subjects and renal patients. PMID- 1508806 TI - Modulation of glutathione levels by non steroidal antiinflammatory drugs. PMID- 1508807 TI - Antidiarrheal effect of deltorphin II, a highly selective delta opioid receptor agonist, in the rat. PMID- 1508808 TI - Use of a retroviral vector for expressing antisense RNA of proopiomelanocortin in AtT-20 cell line. PMID- 1508809 TI - The effect of chronic treatment with phenazone on 3H-serotonin binding sites in pons and cortex membranes of the rat. PMID- 1508810 TI - Possible role of CCKB-receptors in anxiety: an "in vivo" study. PMID- 1508811 TI - Endothelium-independent variation due to age on in vitro rabbit aorta responsiveness. PMID- 1508812 TI - Peripheral ischemia in rabbit hindlimb: effect of cloricromene. PMID- 1508813 TI - Influence of cooling on amiloride positive inotropic effect in isolated atria: role of Na+/Ca2+ exchange. PMID- 1508814 TI - Prostaglandins in rat heart. PMID- 1508815 TI - Facilitating effect of harmaline on the aortic response to dopamine. PMID- 1508816 TI - Effects of melatonin administration on tumor spread in mice bearing Lewis lung carcinoma. PMID- 1508817 TI - Tumor inhibition and effects on host survival time by rutheniumIII and rhodiumIII complexes with dimethylsulphoxide ligands. PMID- 1508818 TI - Short-chain aliphatic halocompounds: "in vivo" effects on microsomal monooxygenase (P450-dependent) system. PMID- 1508819 TI - Post-marketing studies of subjective side effects; a case for strict methodological criteria and careful analysis of data. PMID- 1508820 TI - Verapamil and norverapamil plasma levels in infants and children during chronic oral treatment. PMID- 1508821 TI - Serum concentrations of sodium 2-mercaptoethanesulfonate (MESNA) and its metabolite, disulfide form (DIMESNA), in volunteers after oral dosing: a comparison between MESNA and ARGIMESNA. PMID- 1508822 TI - Signal transduction at the nerve terminal level: role of the phosphorylation of synaptic vesicle proteins. PMID- 1508823 TI - Description of learned response to chronic illness: depressed versus nondepressed self-help class participants. AB - The purpose of this study was to describe the effectiveness of a community-based health-promotion program that was collaboratively designed and that is currently being implemented by lay persons who have the diagnosis of systemic lupus erythematosus (SLE) and by health professionals. Two groups of SLE self-help course participants contributed data for this theory-guided preexperimental program impact study. Braden's self-help model provided the theoretical framework. The variables addressed were severity of illness, limitations, uncertainty, enabling skill self-efficacy, self-worth, and life quality. The groups consisted of 35 subjects having low depression scores (less than or equal to 77) and 37 with high depression scores (greater than or equal to 272) on a measure having a possible range of scores from 0 to 400. Data were collected at three points: at the beginning of class 1, after class 7 (7 wks later), and two months after completion of the course. A group (2) by time (3) by measures (10) MANOVA analysis procedure was used with a follow up univariate F test and Newman Keuls multiple comparison procedure. Significant change was evident for the level of depression group and for three interaction effects of group X time, group X measure, and group X time X measure. PMID- 1508824 TI - Theoretical components of STD counselors' messages to promote clients' use of condoms. AB - A survey of 34 counselors on sexually transmitted diseases from a large Midwestern state was conducted to compare their responses to promote condom use with clients' attitudes and normative beliefs regarding condoms. Four vignettes were developed using predictor variables about condom use based on the theory of reasoned action (TRA). Results indicate subjects responded minimally to TRA variables mentioned in the vignettes. Moralistic messages about condoms were the most frequent responses reported, followed by those on education, disease prevention, and fear. In some cases information provided was not relevant to behavior described in vignettes. Implications for health care professionals are that messages meant to change behaviors should reinforce clients' attitudes and normative influences, and moralistic or fear messages should be minimized. PMID- 1508825 TI - Use of breast cancer screening by older Hispanic women. AB - The purpose of this exploratory study was to provide information on older Hispanic women's access to and use of breast cancer screening services. Interviews were conducted with 150 Hispanic women, 47 to 93 years of age, in a southwestern city. The results indicated that differences in use and compliance with recommended screening guidelines were due primarily to differences in access to the health care system and attitudes about preventive care. Targeted strategies for these women have to be developed and implemented to ensure that they receive the necessary information to avail themselves of breast cancer screening procedures. PMID- 1508826 TI - Tetanus immunity in older adults. AB - The frequency of tetanus has declined little in the past decade. The majority of cases occur in persons over 50 years of age. A sample of 225 blood donors, between the ages of 50 and 68, from a mixed rural-suburban county, were tested for tetanus antitoxin levels. Only 14% had protective levels. This low rate indicates the need for increased attention to tetanus immunizations in older adults. PMID- 1508827 TI - Use of formal community resources by spouse caregivers of chronically ill adults. AB - This descriptive correlational study examined the use of formal community resources of spouse caregivers of progressively chronically ill individuals. The convenience sample was 61 individuals with a definitive diagnosis of multiple sclerosis and their spouse caregivers. Results indicated that 34.4% of the sample used community resources. Relationships among caregiver demographics, extent of caregiving tasks, subjective burden, perceived uncertainty of the caregiver, functional incapacity of the chronically ill individual, level of social support, and the use of formal community resources were analyzed. Positively correlated (P less than 0.05) with the criterion variable of use of formal community resources were the variables of caregiver age (rpb = 0.342), number of caregiving tasks (rpb = 0.424), caregiver employment level (chi 2 = 8.25), and functional incapacity of the care receiver (rpb = 0.565). Results of discriminate function analysis indicated that three variables, functional incapacity, caregiver age, and number of caregiving tasks, correctly classified users versus nonusers of community resources 83.6% of the time. PMID- 1508828 TI - A public health quality assurance system. AB - Quality assurance (QA) systems are commonplace among hospitals. They are even found in home health and health maintenance organizations, but they are less common among public health agencies. This article enumerates the discrepancies between the design of traditional QA and that necessary to meet the needs of a department of health's public health nursing service. It characterizes the subsequent changes that must be inserted into the QA system for it to comply with the mission and services of a public health setting. The system and instruments presented are used in the Baltimore County Department of Health, Public Health Nursing Services. PMID- 1508829 TI - Shifting gears--changing paradigms: a vision for community health nursing. PMID- 1508831 TI - Health care reform and public health nursing. PMID- 1508830 TI - APHA 1991--bringing the message home. American Public Health Association. PMID- 1508832 TI - The concept of poverty. AB - Although poverty is one of the most familiar and enduring conditions known to humanity, it is an extremely complicated concept to understand. Some researchers view it as a reaction to the stress of being poor, whereas others perceive it as a process of adapting to the condition of poverty. Historical definitions are numerous, but can be classified as relating to either lack of financial income or lower social status. Numerous factors contribute to the concept of poverty, including political, economic, social, and cultural forces. The one that has consistently had the greatest effect on the evolving concept is the passage of time, which encompasses all these forces in a very intricate manner. This author explored the evolution of the concept of poverty to identify relevant themes for consideration in the public health nursing domain. PMID- 1508833 TI - Accidental poisoning of children: barriers to resource use in a black, low-income community. AB - This descriptive study examined factors that influence use of poison-prevention measures and poison control center resources in a black, low-income, inner-city community. Convenience sampling was used to recruit 32 mothers of children under age 10 years at two federally funded health centers and two community food pantries. Participants were interviewed using a semistructured interview schedule. Data were analyzed qualitatively, with the results indicating that the majority of mothers had a considerable degree of awareness regarding poisoning susceptibility, severity, and prevention. However, few had access to or had used the poison control center's telephone number. Only 56% had received direct information regarding poisoning, with recall tending to be more accurate when information was obtained outside of the prenatal and postpartum settings. Lack of awareness of poisoning management and poison control center resources was most frequently cited as a barrier. Although this study was limited to one community, it indicates a possible need to distribute culturally acceptable poisoning information and frequent reinforcement for families with small children. PMID- 1508834 TI - Health education and the immigrant Haitian mother: cultural insights for community health nurses. AB - Lack of information about health education from the perspective of immigrants was the basis of a descriptive survey of 30 Haitian mothers in southeast Florida. Subjects were interviewed regarding the value of health education received while seeking preventive health care for infants and preschool children in community health settings, their access to other sources of health education, and their perceptions of what community health care providers could do to assist them in improving child health. Ninety-seven percent took children for well-child care to medical facilities, and 66% received health education during the visits. Seventy percent had access to health-education programs through clinics or the media. Impediments to effective health education were lack of providers who speak Haitian Creole, need for more nurses, and long clinic waiting periods. Nurses were considered the best persons to do health teaching; radio and clinic lectures were the preferred media. Teaching was valuable if it was understandable and practical, reinforced parenting abilities, and allowed time for questions. Results are related to socioeconomic and political factors, traditional Haitian health culture, and cultural views of the cognitive development in children. Culture-specific strategies related to the modes and foci of health education are discussed. PMID- 1508835 TI - Home care during the aftermath of Hurricane Hugo. AB - During the course of field observations for an ethnographic study of home care nurses' job stress, Hurricane Hugo struck the community, causing extensive damage. The nurses' office building was heavily damaged by wind and water, and their office was not habitable for almost a week. The author had observed the nurses' work practices over 10 weeks before the hurricane. In the aftermath of the storm, the nurses were simultaneously disaster victims and caregivers for other victims. They experienced grief, anger, and frustration about their losses, as well as conflict between their family- and work-related responsibilities. Their experiences and behaviors were consistent with those described in prior disaster research literature, lending further support to the earlier studies. A major asset for these nurses was their open, supportive work environment. They were able to accept and affirm one another's negative feelings and to provide support to each other as they dealt with their losses. PMID- 1508836 TI - Acute neurobehavioural toxicity of trichothecene T-2 toxin in the rat. AB - The acute effects of single oral doses, 0.4 and 2.0 mg/kg, of trichothecene T-2 mycotoxin on behaviour, motor performance and nociception were studied in male Wistar rats. Both doses are sublethal and did not cause overt acute signs of intoxication. In the open field test, 2.0 mg/kg of T-2 toxin increased motionlessness and decreased sniffing (P less than 0.05) 4 hr after the administration. The higher dose shortened step-through latencies in the test trial of the 24-hr passive avoidance test (two-way shuttle box). The exponential data analysis showed that, in those rats that did not learn to avoid the dark (unsafe) compartment of the box, the retention after 2.0 mg/kg of T-2 toxin was only 25% of that in controls (P less than 0.001). T-2 toxin had no effect on motor coordination in the rotarod test and in the bridge walking test 7-8 hr after administration. T-2 toxin had no effect on nociception in the hot place test 8.5 hr after administration. The results suggest that T-2 toxin has some inactivating effects on behaviour of rats, and it seems to cause an impairment in the passive avoidance test at dose 2.0 mg/kg. PMID- 1508837 TI - Adipose tissue distribution and chemical structure of basic lipophilic drugs: desipramine, N-acetyl desipramine, and haloperidol. AB - Single-dose intravenous injections of desipramine to rats resulted in a distribution pattern typical of basic lipophilic drugs, i.e., highest concentrations in lung and lowest in adipose tissue and plasma. In contrast, after N-acetyldesipramine, a non-basic analogue of desipramine with comparable lipophilicity, concentrations of this drug in adipose tissue were much higher than in lean tissue or plasma as a result of redistribution into the former and rapid disappearance from the latter tissue. N-Acetyldesipramine had much lower plasma and tissue half-lives than desipramine, but at the same time a much higher adipose/plasma concentration ratio and adipose storage index. Chronic administration of the basic lipophilic drug, haloperidol, to rats in their diet over 21 days resulted in a steady-state distribution pattern with highest concentrations in lung and lowest concentrations without accumulation in adipose tissue. This study provides additional evidence for the influence of basic groups on the distribution of lipophilic drugs. Thus, basic lipophilic drugs do not undergo redistribution into adipose tissues, possibly because of a competition by stronger binding to lean tissue as a result of lysosomotropism. PMID- 1508838 TI - Antinociceptive effects and central nervous system depression caused by oxycodone and morphine in rats. AB - Antinociception and central nervous system depression (CNSD) caused by intraperitoneal, intrathecal and subcutaneous administration of oxycodone or morphine were studied in a randomized and blind, saline controlled study in rats. Antinociception was assessed with the tail-flick and hot plate tests. CNSD was assessed by testing the corneal, placing and righting reflexes and with a 4-point catalepsy score. Intraperitoneally and subcutaneously administered oxycodone and morphine were given in doses of 2.5-10 and 5-20 mg kg-1 respectively. The intrathecal doses were 12.5 micrograms and 100 micrograms of oxycodone and 6.25 micrograms and 50 micrograms of morphine. In both nociceptive tests subcutaneously and intraperitoneally administered oxycodone was 2-4 times more potent than morphine, while intrathecal morphine was over 14 times more potent. CNSD was more profound with oxycodone than with morphine after intraperitoneal and subcutaneous administration, but was not observed after intratechal administration of either drug. Differences in opioid receptor affinities, liposolubilities and metabolism are discussed as possible explanations. PMID- 1508839 TI - Serotonin receptors in the brain of rats treated chronically with imipramine or RU24969: support for the 5-HT1B receptor being a 5-HT autoreceptor. AB - Rats were treated by intraperitoneal injection for four weeks with either RU24969, a 5-HT1B and 5-HT1A agonist or imipramine, a 5-HT uptake inhibitor. Pre- and postsynaptic 5-HT receptors were measured to compare the effect of direct or indirect stimulation of the 5-HT autoreceptor (5-HT1B receptor). The 5-HT transport protein (5-HT uptake site), labelled with [3H]paroxetine, was unaffected after treatment with either one of the drugs. The density of 5-HT2 receptors, labelled with [3H]ketanserin, we found increased after treatment with RU24969 (Bmax = 161 fmol/mg protein) and decreased after treatment with imipramine (Bmax = 109 fmol/mg protein) as compared with control rats (Bmax = 134 fmol/mg protein). The 5-HT1B receptor was found decreased both by the imipramine treatment (Bmax = 106 fmol/mg protein) and the treatment with RU24969 (Bmax = 105 fmol/mg protein), compared with control rats (Bmax = 130 fmol/mg protein). The 5 HT1A receptor was found to be decreased after treatment with RU24969 (control: Bmax = 62 fmol/mg protein; RU24969-treated: 49 fmol/mg protein), but unchanged after treatment with imipramine (Bmax = 58 fmol/mg protein). These results correspond to what could be expected, if the 5-HT1B receptor is the 5-HT autoreceptor. PMID- 1508840 TI - Interactions and comparative effects of zopiclone, diazepam and lorazepam on psychomotor performance and on elimination pharmacokinetics in healthy volunteers. AB - A randomised, placebo-controlled, double blind single-dose cross-over study was arranged to investigate possible interactions between zopiclone (7.5 mg) and two widely used benzodiazepine (BZD) anxiolytics diazepam (5 mg) and lorazepam (1 mg) during the elimination phase of drugs. Psychomotor performance was tested before and 1, 6, 8, 12 and 24 hr after the drug administration. Simultaneously, blood samples were drawn for determination of plasma drug concentrations. The elimination of each compound was not altered by coadministration of other drugs. As expected, one hour after drug ingestion, psychomotor performance was impaired. The coadministration of drugs increased the effect. During the elimination phase, 6 and 8 hr after the drug intake, only zopiclone and lorazepam in combination slightly impaired performance as compared with the pretreatment levels, but there was no difference as compared with placebo. Adverse events after active treatments were not significantly different from those after placebo. At the recommended dose of 7.5 mg, zopiclone does not alter the elimination pharmacokinetics of the BZD anxiolytics diazepam (5mg) and lorazepam (1 mg), and neither is the elimination of zopiclone affected by these BZDs. Due to the rapid elimination of zopiclone, the increase in sedation seen after concurrent administration with BZDs is of short duration. PMID- 1508841 TI - Comparative study of cisplatin and carboplatin on pharmacokinetics, nephrotoxicity and effect on renal nuclear DNA synthesis in rats. AB - To clarify the difference in nephrotoxicity between cisplatin and carboplatin, the pharmacokinetics of platinum, renal function and nuclear DNA synthesis in renal cortical and outer medullary cells were studied in rats which had received cisplatin or carboplatin. Male Sprague-Dawley rats were given either cisplatin or carboplatin intravenously at an equi-toxic dose (LD10 or LD50) and were killed at various times within 7 days after the injection. Cisplatin bound to plasma proteins more avidly than carboplatin. Much more platinum was detectable in the renal nuclei after cisplatin injection than after carboplatin injection. BUN and serum creatinine levels in the rats treated with 8.5 mg/kg of cisplatin were significantly higher than in those treated with 100 mg/kg of carboplatin. Cisplatin markedly suppressed the renal nuclear DNA synthesis both in vivo and in vitro, when compared with carboplatin. It is concluded that the differences in nephrotoxicity between cisplatin and carboplatin are related to their different inhibitory effects on nuclear DNA synthesis in the renal cells. PMID- 1508842 TI - Effects of acute lethal cyanide intoxication on central dopaminergic pathways. AB - In rats treated with sodium cyanide (NaCN), 20 mg/kg intraperitoneally, the striatal dopamine (DA) level was decreased within 60 sec. compared to controls injected with NaCl 0.9%. Treatment with NaCN also increased the naturally occurring L-DOPA in the striatum, but not in the other brain regions studied. Decreased DA levels but increased L-DOPA accumulation were also seen in cyanide treated animals after inhibition of neuronal L-aromatic amino decarboxylase. In rats given a non-lethal dose of NaCN, 2.5 mg/kg intraperitoneally, 30 min. before sacrifice and L-DOPA, 100 mg/kg intraperitoneally, 25 min. before sacrifice, regional L-DOPA levels were not significantly changed, but the striatal DA levels were diminished compared to controls. Decreased DA levels might indicate that cyanide inhibits the synthesis of brain DA. However, both increased L-DOPA and increased accumulation of L-DOPA after neuronal decarboxylase were observed after cyanide. Furthermore, we have earlier reported that lethal doses of NaCN decreased the DA metabolite HVA in the striatum but did not significantly change the oxidatively deaminated metabolite of DA, DOPAC. Inhibition of L-aromatic amino acid decarboxylase appears to play a minor role in causing decreased striatal DA levels. However, our findings might be compatible with cyanide produced inhibition of the energy-demanding granular uptake and/or release of DA. PMID- 1508843 TI - Cathinone, a natural amphetamine. AB - Cathinone is an alkaloid that has been discovered some fifteen years ago in the leaves of the khat bush. This plant grows in East Africa and in southern Arabia, and the inhabitants of these regions frequently chew khat because of its stimulating properties. Cathinone, which is S(-)-alpha-aminopropiophenone, was soon found to have a pharmacological profile closely resembling that of amphetamine; indeed, in a wide variety of in vitro and in vivo experiments it was demonstrated that cathinone shares the action of amphetamine on CNS as well as its sympathomimetic effects; thus, for example, drug-conditioned animals will not distinguish between cathinone and amphetamine. These various observations were confirmed by a clinical experiment showing that cathinone also in humans produces amphetamine-like objective and subjective effects. Finally, it was demonstrated that cathinone operates through the same mechanism as amphetamine, i.e. it acts by releasing catecholamines from presynaptic storage sites. Thus, much experimental evidence indicates that cathinone is the main psychoactive constituent of the khat leaf and that, in fact, this alkaloid is a natural amphetamine. PMID- 1508844 TI - Dopaminergic receptors in hypertension. PMID- 1508845 TI - Brain angiotensin: receptors, actions and possible role in hypertension. PMID- 1508846 TI - Age, hypertension and hypercholesterolaemia alter endothelium-dependent vascular regulation. AB - As a source of several vasoactive factors, the endothelium takes part in the regulation of vascular tone. The most important endothelium-derived vasoactive substances are nitric oxide, prostacyclin, endothelin-1 and contracting factors requiring the activity of cyclooxygenase. The endothelium is an obvious target organ of cardiovascular risk factors. Accordingly, functional alterations do occur with aging, hypertension and hypercholesterolaemia. All three conditions are associated with a decreased basal and simulated release of endothelium derived nitric oxide. On the other hand, the release of endothelin-1 appears to increase with age, while the sensitivity to the peptide markedly decreases under the same conditions. In the spontaneously hypertensive rat, acetylcholine and stretch evoke the release of a cyclooxygenase-dependent endothelium-derived contracting factor, most likely prostaglandin H2. The circulating levels of endothelin-1 on the other hand are not increased in experimental and human hypertension. In the porcine coronary circulation, oxidized low-density lipoproteins selectively reduced endothelium-dependent relaxations to aggregating platelets, serotonin and thrombin which are mediated by nitric oxide. The alterations of endothelial function occurring with aging, hypertension and hypercholesterolaemia may have important clinical implications for the pathogenesis of cardiovascular disease. PMID- 1508847 TI - Proposed guidelines for diagnosis of chromosome mosaicism in amniocytes based on data derived from chromosome mosaicism and pseudomosaicism studies. AB - Currently, accepted protocol which has been developed at the Prenatal Diagnosis Laboratory of New York City (PDL) requires that when a chromosome abnormality is found in one or more cells in one flask, another 20-40 cells must be examined from one or two additional flasks. Chromosome mosaicism is diagnosed only when an identical abnormality is detected in cells from two or more flasks. In a recent PDL series of 12,000 cases studied according to this protocol, we diagnosed 801 cases (6.68 per cent) of single-cell pseudomosaicism (SCPM), 126 cases (1.05 per cent) of multiple-cell pseudomosaicism (MCPM), and 24 cases (0.2 per cent) of true mosaicism. Pseudomosaicism (PM) involving a structural abnormality was a frequent finding (2/3 of SCPM and 3/5 of MCPM), with an unbalanced structural abnormality in 55 per cent of SCPM and 24 per cent of MCPM. We also reviewed all true mosaic cases (a total of 50) diagnosed in the first 22,000 PDL cases. Of these 50 cases, 23 were sex chromosome mosaics and 27 had autosomal mosaicism; 48 cases had numerical abnormalities and two had structural abnormalities. Twenty five cases of mosaicism were diagnosed in the first 20 cells from two flasks, i.e., without additional work-up, whereas the other 25 cases required extensive work-up to establish a diagnosis (12 needed additional cell counts from the initial two culture flasks; 13 required harvesting a third flask for cell analysis). Our data plus review of other available data led us to conclude that rigorous efforts to diagnose true mosaicism have little impact in many instances, and therefore are not cost-effective. On the basis of all available data, a work up for potential mosaicism involving a sex chromosome aneuploidy or structural abnormality should have less priority than a work-up for a common viable autosomal trisomy. We recommend revised guidelines for dealing with (1) a numerical versus a structural abnormality and (2) an autosomal versus a sex chromosome numerical aneuploidy. Emphasis should be placed on autosomes known to be associated with phenotypic abnormalities. These new guidelines, which cover both flask and in situ methods, should result in more effective prenatal cytogenetic diagnosis and reduced patient anxiety. PMID- 1508848 TI - Transvaginal sonography-detection of findings suggestive of fetal chromosomal anomalies in the first and early second trimesters. AB - Over a 4-year period, 14 dyskaryotic fetuses were diagnosed by amniocentesis, performed after early detection of malformations using transvaginal sonography (TVS). These 14 dyskaryotic fetuses were detected out of 4878 sonographic screenings performed by TVS between 9 and 16 weeks' gestation. Twenty-eight per cent of the referrals were at high risk and 72 per cent were at low risk for fetal malformations. Two hundred and twenty-nine fetuses (4.7 per cent) of the screened population had 265 anomalies, 39 per cent of them being transient. In 7 of the 14 dyskaryotic fetuses (50 per cent), the sonographically detected anomalies were transient, being undetected by follow-up sonographic screenings at later gestational ages (greater than or equal to 18 weeks). Postponing the first sonographic scan aimed at malformation detection to a later gestational age may lead to transient anomalies and their associated dyskaryosis being missed. PMID- 1508849 TI - First trimester amniocentesis between the seventh and 13th weeks: evaluation of the earliest possible genetic diagnosis. AB - Amniocentesis performed at the 12th week and later gives reliable results. The procedure can be performed using regimens developed for mid-trimester amniotic fluid (AF) cells. Extension to the 10th-11th week is, in principle, feasible. However, the high cytogenetic failure rate is a difficulty and despite a high clone count, the culture time is prolonged. The problem of the relatively high loss of AF could be overcome by cell filtration techniques and replacement of the fluid. Because of the short turnover rate of the AF, this may be unnecessary or replacement with an isotonic solution may be sufficient. (Pseudo)mosaicism appears to occur more frequently in early than in late amniocentesis. As yet, data are too sparse to allow a comparison with chorionic villus sampling. There are no reliable follow-up data from which to estimate the abortion rate and the number of embryonic malformations. PMID- 1508850 TI - Mutation analysis for prenatal diagnosis and heterozygote detection of Gaucher disease type III (Norrbottnian type). AB - A single base substitution in exon 10 of the glucocerebrosidase gene was detected in families affected by Gaucher disease (GD) type III. This mutation, which results in the substitution of proline for leucine in position 444 of glucocerebrosidase, has been shown to result in type III GD in a Swedish population. Three fetuses at risk for GD type III were diagnosed as homozygous for the mutation and the pregnancies were terminated. In a fourth pregnancy, one parent was excluded as being a carrier and the risk of having a child affected by GD was ignored. Direct analysis of common mutations causal to GD is now available and improves prenatal diagnosis in families where the molecular defect has been characterized. PMID- 1508851 TI - First-trimester amniotic fluid and extraembryonic coelomic fluid acetylcholinesterase electrophoresis. AB - Acetylcholinesterase (AChE) gel electrophoresis was performed on samples of amniotic fluid and extraembryonic coelomic fluid obtained by high resolution transvaginal ultrasound-guided amniocentesis from 38 women between 8 and 12 weeks of pregnancy. AChE was positive in 33 per cent (12/36) of the amniotic fluid samples; the percentage of positive results decreased as gestation advanced. AChE was positive in 32 per cent (9/28) of the extraembryonic coelomic fluid samples. In 81 per cent (21/26) of matched samples, the AChE results were identical in the two fluids. Amniotic fluid and extraembryonic coelomic fluid AChE electrophoresis cannot be used to diagnose neural tube defects prior to 12 weeks of gestation. PMID- 1508852 TI - Cytogenetic experience in prenatal fra(X) detection on amniotic fluid cultures. AB - Since 1987, we have had experience with 13 prenatal diagnoses of 11 women at risk for the fragile X syndrome by cytogenetic studies on amniotic fluid cultures. The induction method included TC 199 medium and methotrexate. Results were obtained in all cases. Ten were males and three were prenatally diagnosed as being affected. Three were females and none of them was fra(X)-positive. Results were confirmed in 10/13 cases. In these cases, we had neither false-positive nor false negative results. PMID- 1508853 TI - Early twin amniocentesis prior to 14 weeks' gestation. PMID- 1508854 TI - Confirmation of CVS mosaicism. PMID- 1508855 TI - Maternal serum hCG levels in triploidy: variability and need to consider molar tissue. PMID- 1508857 TI - [Incidence of clinical autopsy in relation to refusal and consent at the Hannover Medical School]. PMID- 1508856 TI - [Clinical aspects, morphology and biology of prolactinomas after therapy with dopamine agonists. A review of the literature]. PMID- 1508858 TI - [Groove pancreatitis]. PMID- 1508859 TI - [Epitheloid hemangioma]. PMID- 1508860 TI - [Intravascular form of angiomyolipoma of the kidney. Case report and review of the literature]. PMID- 1508861 TI - [Metastatic malignant glucagonoma]. PMID- 1508862 TI - [GAVE syndrome: a rare cause of occult gastrointestinal hemorrhage]. PMID- 1508863 TI - [Sweat gland necroses in acute alcoholic intoxication]. PMID- 1508864 TI - [Cystitis glandularis of the intestinal type (= intestinal metaplasia) in the urinary bladder mucosa with functionally significant pseudotumor formation]. PMID- 1508865 TI - [Primary unilocular mucinous cystadenoma of the retroperitoneum--a contribution to the origin]. PMID- 1508866 TI - Factors regulating and modifying dental root resorption. AB - A comparison is made between the resorption of bone and the resorption of the mineralized tissues of teeth. The structure and function of osteoclasts are described well as the factors that regulate their activity. The cells resorbing the dental mineralized tissues are of the same cell type as osteoclasts. The dental tissues are covered by cementoblasts or odontoblasts which differ from the osteoblasts in that they do not respond to hormones and cytokines that stimulate bone resorption. Root resorption therefore seem to require damage of the cementoblastic layer in combination with necrosis or inflammation or replacement of the cementoblastic layer by osteoblasts. The root resorption that occurs at the shedding of the primary teeth is induced in a different way possibly by substance(s) from the reduced enamel epithelium. There seems to be no systematic study on the frequency and extension of root resorption in association with inflammatory or neoplastic conditions. It is suggested that dentigerous cysts and some epithelial tumors induce root resorption in the same way as the erupting tooth. The mechanisms by which some other tumors or tumor-like conditions cause root resorption are essentially unknown. PMID- 1508867 TI - Relation of dentin sensitivity to histological changes in dog teeth with exposed and stimulated dentin. AB - The effect of chronic exposure of dentin to the sensitivity of intradental nerves was studied in dogs. The dentin of canine and incisor teeth was exposed one week prior to the experiments in which 34 single fiber units dissected from the inferior alveolar nerve were recorded. In the teeth with acutely bared dentin 36 nerve fibers were tested. SEM of the chronically exposed dentin showed that practically no tubule apertures could be found since the surface was covered with bacteria and oral debris. This coating had to be removed by drilling and acid etching before any responses could be evoked. When compared to the teeth with acutely exposed dentin, the sensitivity of the fibers responding to drilling, probing, osmotic stimulation, and air blasts applied to the dentin was weakened in the chronic cases, in the sense that fewer units of those tested responded. However, cold evoked nerve activity only in some chronically exposed teeth, suggesting sensitization of the nerves. TEM revealed electron-dense substance in the dentinal tubules of the chronic teeth. Some of the material was evidently cellular remnants aspirated from the pulp and some of it, staining more faintly, could be extravasated plasma proteins. In the acute cases the tubules were emptier. Light microscopy showed histological injuries in the pulp-dentin border. It is concluded that the decrease in the responsiveness of the pulp nerve fibers in the chronic cases was due to the changes in the dentin. PMID- 1508869 TI - Effect of aging and caries on dentin permeability. AB - Extracted human teeth were collected from young (20-28 yrs) versus old (45-69 yrs) patients. The teeth were divided into carious and noncarious groups. Slabs were created from the mid-coronal occlusal dentin. Carious lesions were excavated and the smear layers on both normal and excavated carious dentin were removed with 37% phosphoric acid (1 min). The permeability (hydraulic conductance) of old normal dentin was only 20% of that obtained in young normal dentin but all of the specimens were permeable. Young carious dentin was only 14% as permeable as young normal dentin and only 1 out of 7 specimens was not permeable. All 7 specimens of old carious dentin were impermeable. Scanning electron microscopy of old and carious dentin exhibited far more intratubular crystals than normal dentin, providing a structural basis for the functional observation. PMID- 1508868 TI - Effect of serotonin (5-HT) and calcitonin gene-related peptide (CGRP) on the function of intradental nerves in the dog. AB - Several inflammatory mediators including serotonin (5-HT) have been indicated to play a role in the sensitization of intradental nerves. In the present investigation, using the single fibre recording technique, the effect of locally applied 5-HT (1 mg/ml) and calcitonin gene-related peptide (rat CGRP 2 micrograms/microliters) on the function of intradental nerves in the dog was studied. The effect of these substances on the pulpal blood flow was also investigated to check their effective diffusion into the dental pulp. 5-HT induced a low-frequency background firing in 11 out of 30 nerve fibres. The number of fibres responding to probing, air blast and osmotic stimulation was increased significantly after 5-HT application. Three fibres responded to cold stimulation after 5-HT application; no responses were induced before. After CGRP application, a continuous low-frequency firing was induced only in 1 fibre out of 11 and 1 fibre which before did not respond to osmotic stimulation gave responses to saturated glucose. The responses to probing and air blasts were qualitatively unchanged. Local application of either of the substances induced a change in pulpal blood flow. It is suggested that while 5-HT is able to sensitize intradental nerves to various hydrodynamic stimuli, CGRP seems to be less effective. Pulpal inflammation with the release of inflammatory mediators may significantly affect the degree of dentine sensitivity. PMID- 1508870 TI - Neurophysiological mechanisms of dentin hypersensitivity. AB - In hypersensitive teeth pain is typically induced by cold and hot fluids or foods brought to contact with the sensitive dentin or by osmotic and mechanical stimuli. The results of animal experiments indicate that intradental A-type nerve fibres are responsible for the sensitivity of dentin. They are most probably activated by the hydrodynamic mechanism. Thus, their activation is to a great extent dependent on the condition of dentin with either open or blocked dentinal tubules. Blocking of the tubules effectively prevents the nerve activation. Correspondingly, in human experiments, the condition of the dentinal tubules greatly affects dentin sensitivity. In clinical studies significantly more open tubules are found in sensitive compared to non-sensitive areas. However, hypersensitivity may sometimes persist despite of effective blocking of the tubules. This may indicate that some other mechanisms may operate in the nerve activation instead of, or in addition to the hydrodynamic one. Inflammation may sensitize the nerve endings to such an extent that smaller fluid shifts would be sufficient for nerve activation or, for example, thermal stimulation may activate the nerves by a direct effect. On the other hand, spontaneously occurring changes in the exposed dentin, which in many cases seem to block the tubules may reduce the responses to hydrodynamic stimulation and, thus, have an opposite effect on dentin sensitivity. The results of animal experiments indicate that functional changes of this kind may occur. These results also indicate that real dentin hypersensitivity can develop as a result of inflammation induced sensitization of the nerves in the pulp-dentin border in teeth with open dentinal tubules.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1508871 TI - Factors influencing the occurrence of pain in carious teeth. AB - The mechanisms by which pain develops in carious teeth are poorly understood. The variability of dentin and pulp responses to carious attack is probably the cause for the variations in the pain symptoms presented by patients. This article is a review of the available data regarding the changes that dentin and pulp undergo in carious teeth. Such changes are discussed in relation to their possible influence on intradental sensory nerve excitability. Special emphasis is given to the various bacterial metabolites produced and accumulated in carious dentin and their ability to modulate pain symptoms from carious teeth. PMID- 1508872 TI - Effects of CO2 laser irradiation on pulpal blood flow. AB - CO2 laser may be beneficially applied to teeth in preventive and restorative dentistry, but its physiopathologic effects on the dental pulp have not been reported. To address the dynamic pulpal changes induced by CO2 laser the purpose of this study was to examine such changes in pulpal microcirculation. The enamel surfaces of 4 cat canines were irradiated by CO2 laser beam, delivered by either a handpiece or microslad with a focal spot diameter of 0.21mm and 0.33mm, respectively. Exposure powers of 2.6-20 W were used for durations of 0.05-0.2 sec, resulting in energy density range of 304-1440 J/cm2. Non-invasive measurement of pulpal blood flow (PBF) by a laser Doppler flowmeter was maintained continuously before and following CO2 laser irradiation. CO2 laser irradiation resulted in an immediate increase in PBF, which subsided after 2-3 min. Large pulps responded with a significantly higher PBF increase than small pulps. These results confirm that CO2 laser irradiation of the tooth surface has a thermal effect on the pulp, which is moderated by the insulating capability of dentin. It appears that the associated thermal damage is not extensive when laser exposure parameters are such as used herein. PMID- 1508873 TI - Changes in expression of alpha 1 type 1 collagen and osteocalcin mRNA in osteoblasts and odontoblasts at different stages of maturity as shown by in situ hybridization. AB - We investigated whether the expressed phenotype of osteoblasts and odontoblasts is changing with increasing maturity of the cells. Thus we determined, using in situ hybridization techniques, whether the expression of mRNA's for osteocalcin and the alpha 1 type 1 collagen chain was different in newly developed and more mature cuboidal osteoblasts of the primary and secondary spongiosa of radii of 8 day old rats, in mature cuboidal and older flat osteoblasts in the metatarsals of pig embryos, and in apical and coronal odontoblasts of the developing unerupted molars of pig embryos. The results indicate that newly differentiated osteoblasts in the primary spongiosa of the 8 day rat radius contained approximately the same amount of type 1 collagen message as more mature osteoblasts in the secondary spongiosa. Osteocalcin mRNA, on the other hand, was undetectable in the newly differentiated osteoblasts but clearly detectable in the mature osteoblasts of the secondary spongiosa. When we compared expression of osteocalcin and collagen type 1 mRNA in mature cuboidal and older flat osteoblasts, we found that the amount of osteocalcin mRNA relative to collagen type 1 mRNA was higher in flat osteoblasts than in cuboidal osteoblasts. In odontoblasts, however, the steady state level of collagen type 1 mRNA was higher in the older coronal odontoblasts, and the level of osteocalcin message lower, when compared to the younger apical odontoblasts. The results indicate that relative levels of osteocalcin and collagen mRNA in osteoblasts and odontoblasts vary depending on the stage in their secretory lifetime. This heterogeneity of the osteoblast and odontoblast population suggests that the composition of the matrix produced by these cells also differs. PMID- 1508874 TI - Repair dentinogenesis following transplantation into normal and germ-free animals. AB - The purpose of this study was to investigate the dentinogenesis of dental pulp tissue following transplantation and during regeneration in normal and germ free animals, as well as in vitro experiments. EXPERIMENTS: (1) Partial and complete exposure of dental pulp in germ free rats by removing the enamel and dentin of molars. (2) The central portion of rat incisor which consisted of pulp and pulp chamber were autografted into various tissues. (3) Explants of rat pulp tissue were cultured on dentin matrix. (4) Resin bonding agent, 4-META/MMA-TBB-O (Superbond), was placed directly on surgically-exposed dental pulp. RESULTS: (1) Dentin bridge formation was recognized at 5 days after operation in germ free rat. (2) The cut surface of the transplant exhibited dentin bridge at 7 days after implantation, and the thickness of the newly formed dentin increased gradually thereafter up to 30 days. (3) Cultured pulp cells had high alkaline phosphatase activity and bone- or dentin-like hard tissue was synthesized on the dentin matrix in vitro. (4) Dentin bridge formation was evident on the surgically exposed dental pulp even after application of Superbond. From these results, it is suggested that pulp tissue has a high activity of dentinogenesis both in vivo and in vitro and 3 days is enough for pulp cells to express the odontoblast phenotype when inflammatory factors are not present. PMID- 1508875 TI - Dentin phosphoprotein in dentin development: implications in dentinogenesis imperfecta. AB - Dentin phosphoprotein (DPP, phosphophoryn) is the major non-collagenous protein component of the dentin extracellular matrix. This highly acidic phosphorylated protein is solely expressed by ectomesenchymal-derived odontoblast cells of the tooth organ. Previous biochemical studies have suggested the absence of this protein associated with the human genetic disease dentinogenesis imperfecta (DGI) Types I and II. However, due to the normal degradation of human DPP during dentin maturation, it has not been possible to establish if these reported differences were due to changes in DPP expression or secondary degradation rates in DGI affected versus normal teeth. Recently, we have taken both a molecular and biochemical approach to address this problem. Molecular studies have utilized genetic linkage studies performed on several multi-generation informative DGI kindreds. These studies have determined linkage between DGI Types II and III and two markers localized to the long arm of human chromosome 4 in the region 4q11 4q21. The strategy used in our study was to map the DPP gene locus to the long arm of human chromosome 4, in the same region as DGI, using a DPP oligonucleotide probe and somatic hybrid cell lines. The results indicate DPP is not localized to any region of human chromosome 4. Our data indicates that a mutation within the DPP gene locus is not associated with DGI Types II or III. This data is supported by the identification of human DPP (95 kDa) within the dentin extracellular matrix of molars isolated from an affected DGI type II patient using a mouse anti DPP antibody. However, this does not exclude the possibility that enzymes associated with DPP post-translational modifications (ie. phosphorylation or degradation) might be responsible for this genetic disease. PMID- 1508876 TI - Molecular control of dentinogenesis: a reaction. AB - This paper represents an invited reaction to three papers presented at the International Conference on Pathobiology of the Dentin/Pulp Complex, June, 1991. Repair dentinogenesis following transplantation into normal and germs free animals are correlated with results elucidating the expression of dentin phosphoproteins, collagen, and osteocalcin. The importance of transcription and translation controls of dentin matrix components are discussed and reviewed. In addition, possible implications of a molecular chaperone protein, Hsp47, in controlling dentinogenesis is introduced. Future research directions are developed and include: (a) identification of odontoblast precursors; (b) delineation of markers for odontoblasts at varying degrees of differentiation; (c) characterization of environmental conditions leading to odontoblast differentiation; (d) determination of the nature of repair and regenerated tissues; (e) elucidation of transcription and translation control factors, and (f) mapping the human genome for dentin matrix constituents. PMID- 1508877 TI - Smear layer: overview of structure and function. AB - Smear layers are created on hard tissues whenever they are cut with hand or rotary instruments. This thin (1-2 microns) layer of denatured cutting debris is very tenacious and, in fact, is often the surface to which restorative materials are luted. The solubility characteristics, chemical reactivity and the structure function relationships of this layer have not yet been well-defined. During creation of the smear layer, cutting debris is forced variable distances into dentinal tubules. These so-called smear plugs, together with the smear layer decrease dentin permeability, dentin sensitivity and surface wetness. Bonding adhesive resins to smear layers appears to limit the theoretical bond strength unless the smear layers are loosened or partially removed. Future research in this area will include the use of surface analytical techniques such as Auger electron spectroscopy and ESCA. These techniques are required because of the thinness of the smear layer. It is clear that the nature of this critical interface between dental materials and cut hard tissues remains largely unknown. This field will provide fertile ground for future research. PMID- 1508878 TI - Smear layer--materials surface. AB - SEM and TEM photomicrographs were presented of the smear layer and several dentin adhesive interfaces. It was shown that as the wetting and penetration of the dentin adhesive increased, the shear bond strength also increased. Three categories of dentin adhesives were presented. Category one included Scotchbond, Dentin Adhesit and Gluma, with shear bond strength values between 5 and 7 MPa; the second category, dentin adhesives based on Dr. Bowen's research, included Tenure and Mirage Bond, with shear bond strengths between 8 and 14 MPa; the third category included Superbond and Scotchbond 2, with shear bond strength values up to 20 MPa. Failures occurred at the interface or in the resin adhesive for materials in categories one and two; failures occurred through the dentin or composite for materials in category three. PMID- 1508879 TI - Clinical aspects of dentine hypersensitivity. AB - Dentine hypersensitivity is a common painful condition about which relatively little is known. A review of the literature reveals that most research has been concerned with the clinical assessment of therapeutic agents. However, even here there is little information concerning the actual mode of action of such agents. Many clinical aspects of the condition also appear anecdotal at best and there is always a need to consider a differential diagnosis to exclude other causes of dentinal pain. Detailed prevalence figures are not available for dentine hypersensitivity as it affects different groups, although age and possibly gender differences are apparent. Additionally, the condition shows predilections for certain oral sites which may be of aetiological relevance. Consistent with the hydrodynamic theory hypersensitivity lesions reveal large numbers of widened dentinal tubules at the surface and patent to the pulp. The use of dentine replica techniques could prove useful in objectively studying the condition and monitoring treatments. It is apparent that in clinical management little attention has been paid to factors which expose dentine and open tubules. Without consideration of aetiological factors the management of Dentine Hypersensitivity may be compromised. PMID- 1508881 TI - Odontoblast response under carious lesions. AB - The local regulation of odontoblast response to caries is viewed through initiation and elaboration of sclerotic as well as reparative dentin. Dentin tissue represents a multiple source of potent environment factors when teeth are affected by the demineralization phases of carious process. Some of them have already been identified in sound tissue (matrix glycoproteins, proteoglycans, growth factors, Bone Morphogenetic Protein) and may act on the cell through membrane receptors. Thus, the amplification in collagen synthesis and alkaline phosphatase activity previously observed during sclerotic dentin deposition can be related to the interaction between matrix signals and cell receptors such as the 165 kDa protein shown only by odontoblasts under the affected zone. Similarly, under established lesions generating cell death, the specific matrix made of odontoblasts debris and damage tissues, probably rich in active molecules, may trigger pulp cells to elaborate a cartilage-like layer (identified by type II and XI collagen) followed by odontoblast-like cells to give rise to abnormal tubular dentin. Here, odontoblast response is identical to bone-cells response to injury. What remains to be elucidated concern: The nature of signals found in carious dentin (matrix components, growth factors, bacterial products). The nature and regulation of expression of cell membrane receptors during tooth repair. How the odontoblast produces specific responses to each of these signaling molecules will be the focus of important new investigations. PMID- 1508880 TI - An ultrastructural and autoradiographic analysis of primary and replacement odontoblasts following cavity preparation and wound healing in the rat molar. AB - Numerous studies using various animal and human models have reported changes in the morphology and metabolic activity of primary odontoblasts in the mature tooth pulp after perturbations of the tooth including cavity preparation and restoration, pulpal exposures and pulp capping with various capping agents. The first part of this study investigated changes in primary and replacement odontoblast activity after cavity preparation or pulpal exposure. Two groups of rats were used in this investigation. One group of rats had Class V cavities prepared to the DEJ of the first maxillary molars. These rats were immediately injected with 3H-proline and killed 15, 30 or 60 minutes later. Rats killed at day 1, 3, 5, 7, 10 or 14 were injected one hour prior to sacrifice. The second group of rats each had a pulp exposure that was capped with a calcium hydroxide containing material and restored with a composite resin. Rats were sacrificed as previously described. Tissue was processed routinely for ultrastructural analysis and E.M. autoradiography. The second part of this study consisted of an injection of 125I-fibrinogen one hour prior to a class V cavity preparation 1/2 the distance through dentin thickness. Rats were sacrificed at 5, 10, 15 and 30 minutes postsurgery. Differences in the location and distribution of the reduced silver halide grains were recorded as well as differences in the amount and distribution of the various organelles measured between primary and replacement odontoblasts. The results of this study suggests that primary and replacement odontoblasts were morphologically and physiologically dissimilar at the time periods tested in this study. 125I-fibrinogen was demonstrated within the dentinal tubules and in the floor of the cavity preparation as early as 5 minutes after completion of the cavity preparation. The preliminary results of the 125I fibrinogen suggest that operative trauma can effect very rapid changes to the dental pulp leading to leakage of plasma proteins from the circulation, between odontoblasts, out of the tubules to the cut dentin surface. PMID- 1508882 TI - Dentin/pulp complex reactions: a reaction. PMID- 1508883 TI - Preliminary studies on pulp capping with demineralized dentin. AB - The use of osteoinductive demineralized dentin matrix in the repair of vital pulp exposures was examined. The pulps of the maxillary first molars of adult male Long Evans rats were exposed and capped with either demineralized dentin particles or guanidinium extracted demineralized dentin particles; then covered with a glass ionomer cement restoration. The animals were sacrificed after two weeks and the maxillae were dissected free, fixed in formaldehyde and demineralized. Histologic examination revealed that in those cases where the protective glass ionomer restoration was intact, both groups showed some healing. There was some preliminary indication that the extent of reactive matrix formation was greater in the osteoinductive group. In both groups, odontoblast like cells appeared to incorporate some of the dentin particles into the reparative dentin bridge. This preliminary work suggests that osteoinductive factors present in demineralized incisor dentin might be used to guide the formation of a dentin bridge in a rat model for vital pulp exposures. PMID- 1508884 TI - Genetic marker study of dentinogenesis imperfecta. AB - DGI-II has been linked to the group specific component (Gc) on 4q and to interferon induced protein 10 (INP10) on 4q. We studied a three generation family with DGI-II along with a four generation DGI-II family to more precisely place DGI-II in the existing genetic map of 4q and to determine if genetic heterogeneity existed between various DGI-II families. Affected family members had brownish discoloration of the teeth, enamel fracturing and radiographic evidence of coronal and radicular pulp chamber obliteration. Thirteen polymorphic markers on 4q were studied including D4S35, D4S1, ALB, Gc, MGSA, AR, INP10, ADH3, FGFB, EGF, IL2, IF, and MNS. Gc and MNS blood group antigen typing were done using commercial SERA. Restriction fragment length polymorphism analysis using Southern blotting was done on the remaining markers. Pairwise linkage analysis was performed using the procedures of Morton. Tight linkage between DGI-II and eleven genetic markers, including Gc and EGF, was excluded. The tightest linkage with DGI-II was identified with the probe INP10 at theta = 0.0 with lod = +3.91. However, INP10 RFLP differences were detected between the families, such that DGI II correlated with different alleles in each family. Results from this study demonstrated that DGI-II may possibly arise from more than one genetic mutation. PMID- 1508885 TI - The isolation and primary culture of putative human root odontoblasts. AB - The use of procedures adapted from a routinely successful method of culturing bovine bone has led to the first system for the study of dentinogenesis in vitro. Two types of cells have been grown from pulp obtained from the growing root tips of impacted third molars extracted from 14- to 19-years olds: (1) epithelial-like cells that are probably derived from fragments of the epithelial root sheath and (2) odontoblast-like cells. The cultured epithelial-like cells grow out in distinctive rounded plaques while the odontoblast-like cells are tethered to and/or grow on top of the epithelial-like cells. The odontoblast-like cells produce mineralized matrix by 10 days when cultured on a defined mineralization formula containing conditioned medium obtained from fetal bovine bone cell cultures. Growth factors in this conditioned medium are important to cell proliferation and growth and to the synthesis of mineralized matrix. Sequential enzyme digestion in dispase and dispase/collagenase in serum-free Dulbecco's Modified Eagle's Medium is essential to obtaining adequate cell yields from the apical 3-5 mm of the developing root. Reduction of the number of fibroblasts by treating cultures with dispase in Tyrode's solution midway through the initial growth period enhances the purity of these cell cultures. PMID- 1508886 TI - Dentin permeability and dentin sensitivity. AB - The hydrodynamic theory of dentin sensitivity is based on the premise that sensitive dentin is permeable throughout the length of the tubules. Such a condition may permit the diffusion of bacterial products across dentin to the pulp where they may cause irritation of pulpal soft tissues. However, the slow outward movement of dentinal fluid tends to flush the tubules free of exogenous substances. This balance between the inward diffusion of exogenous substances, whether bacterial or the active ingredients in desensitizing medicaments, and the cleansing action of dentinal fluid flow needs to be examined experimentally. PMID- 1508887 TI - Odontoblast-mediated regulation of the progression of dentinal caries. AB - Osteoblasts and odontoblasts are both derived from the same mesenchymal cell line. Our aim was to investigate whether the processes of bone destruction and dentinal caries are biologically similar. The working hypothesis was that after the initiation of caries in the enamel, its rate of progression in the dentine is regulated by cell-mediated factors. Experimental caries was induced in the rat with a high sucrose diet combined with Streptococcus sobrinus infection. Both destruction of dentine and its apposition in the pulp under the carious lesions were measured after vital staining with tetracycline. Caries progression and dentine apposition were higher in developing teeth prior to apex "closure" than in adult, fully-formed teeth. Rats placed on a cariogenic diet during tooth development had an increased rate of caries progression. Fluoride administration via the drinking water was associated with decreased dentine apposition and little progression of dentine caries during the developmental stages. Dentine apposition was enhanced in adult rats placed on fluoride administration, while caries progression was reduced, whereas in animals subjected to metabolic acidosis dentine caries progression was enhanced, with reduced dentine apposition. In contrast, alkalotic animals had less dentinal lesions and smaller ones than the controls. Three theories are advanced to explain the observed changes: (i) They may be associated with changes in alkaline phosphatase activity in the pulpo-dentinal complex, (ii) they may be mediated by ionic changes in the dentinal fluid, or (iii) they may reflect the liberation of growth factors from dentinal matrix. PMID- 1508888 TI - The hybrid layer: a resin-dentin composite. AB - During studies designed to improve the bonding of adhesive resins to tooth structure, it was found that methacrylates with both hydrophobic and hydrophilic groups promoted monomer penetration into suitably prepared dentin. The monomers impregnated and became entangled with the collagen fibrils of surface demineralized dentin, creating a hybrid layer after their polymerization. The identification, properties and function of the hybrid layer, a new biologic composite, are explained. PMID- 1508889 TI - Extracellular fluid movement in the pulp; the pulp/dentin permeability barrier. AB - Fluid movement in the pulp depends largely upon the physiology of the blood vessels; normally there is a net efflux of fluid and proteins from the capillaries into the extracellular environment. Most pulp capillaries lie close to the odontoblast layer and in order to see whether fluid can pass between the odontoblasts into the predentin we have perfused the vessels of molar tooth germs in anesthetized piglets with the electron dense tracer lanthanum. The results show that the tracer permeates the capillaries but encounters a barrier to permeability at the apical (predentinal) ends of the odontoblasts. The completeness of the barrier to the tracer lanthanum is discussed together with structural evidence of tight junctions between odontoblasts in both pigs and humans and the presence of collagen fibers through the tight junctional zone. It is concluded that there is little or no evidence that pulp fluid is normally confluent with predentin. An advantage of this arrangement may be that by maintaining an enclosed microenvironment it permits regulation of the orderly process of matrix deposition and mineralization of predentin to dentin. In order to maintain constant vascular and extracellular fluid pressures the capillary efflux has to be balanced by fluid removal; recent work in cats has shown that lymphatic vessels are available to transport fluid out of the pulp. In this paper the differences in the intrapulpal distribution of these vessels have been extrapolated to human teeth in an attempt to explain certain variations in the symptoms and progress of pulpal inflammatory conditions. PMID- 1508890 TI - Accessory cells in the immune defense of the dental pulp. AB - This communication focuses on the participation of accessory cells in the initial recognition and processing of antigenic substances in the dental pulp. Immunohistochemical analyses have demonstrated the presence of two types of accessory cells--one with a dendritic morphology located in the periphery of the pulp and one with a macrophage-like appearance located more centrally. Functional studies in vitro have provided evidence for the dendritic cells being the most significant of the two cells regarding their capacity to induce T-cell proliferation. Studies on ontogeny have revealed that the appearance of pulp accessory cells is delayed compared to other peripheral tissues. In experimentally induced pulp lesions a rapid increase of cells with morphologic and phenotypic features similar to normally occurring accessory cells was found. These data demonstrate that the dental pulp contains the necessary cellular constituents to mount an immunologic defense reaction. Future studies should focus on elucidating possible interactions between these immune cells and the neurovascular system of the pulp. PMID- 1508891 TI - The role of growth factors in determination and differentiation of the odontoblastic cell lineage. AB - In developing teeth the differentiation of odontoblasts is triggered by the enamel epithelium and is tightly coupled with morphogenesis. There is substantial evidence that even in mature teeth the cells of the dental pulp retain the capability to differentiate into odontoblasts under suitable conditions. However, cells from other than the dental mesenchymal cell lineage apparently do not possess this potential. Thus, it is conceivable that the dental mesenchymal cells acquire cell type-specific potential to differentiate into odontoblasts during their developmental history. Therefore, the understanding of the mechanisms which regulate the terminal differentiation of odontoblasts requires that the molecular changes and mechanisms that are associated with their progressive determination be clarified. It can be speculated that there are key transition points in the developmental sequence during which the mesenchymal cells acquire new levels of differentiation. These include, (1) the condensation of the neural crest-derived mesenchymal cells around the epithelial bud, (2) their entrance into the dental papilla lineage during cap stage, and (3) the differentiation of the cells underlying the enamel epithelium into odontoblasts during bell stage. The transition points are conceivably characterized by amplification or onset of expression of new sets of genes encoding transcription factors, growth factors as well as structural proteins. We have applied in situ hybridization for localization of the expression of two growth factors during mouse molar morphogenesis: transforming growth factor beta 1 (TGF beta 1) and int-2 (a proto oncogene coding for a fibroblast growth factor-related protein). During bud stage, expression of TGF beta 1 was first detected in the epithelium and shortly thereafter in the condensed dental mesenchyme. The expression was weak during early bell stage but a high number of transcripts appeared in secretory odontoblasts as well as in presecretory ameloblasts. int-2 mRNA appeared in the dental papilla mesenchyme at the onset of cap stage, persisted in the cuspal mesenchyme during bell stage and was lost upon completion of morphogenesis. Our findings suggest that cell type-specific expression of TGF beta 1 and int-2 is associated with phenotypic properties of the odontoblastic cell lineage. For instance, TGF beta 1 may regulate matrix deposition by increasing tenascin and syndecan expression in the condensed dental mesenchyme and by controlling dentin matrix deposition by odontoblasts. TGF beta 1 and int-2 may also be involved in signalling between the epithelial and mesenchymal tissues and in regulation of gene expression at the transition points of the developmental sequence that leads to the differentiation of odontoblasts. PMID- 1508893 TI - Regulatory factors in pulp biology: a reaction. AB - A number of developmental processes can be investigated in the mammalian pulp. Of particular interests are those developmental processes related to when, where and how specific phenotypes are expressed in the forming pulp tissues. This "reaction" attempts to highlight the basic processes related to immunological factors associated with accessory cells, growth factors and the determination and differentiation of odontoblasts, and dentin-specific non-collagenous proteins. The three papers associated with these developmental processes provide an exciting glimpse into the emerging advances being made in pulp biology. PMID- 1508892 TI - Recent investigations on dentin specific proteins. AB - Several extracellular matrix (ECM) proteins have been isolated from dentin and shown to be synthesized by odontoblasts. Highly phosphorylated proteins (HP), the phosphophoryns, are specifically found in dentin and are synthesized only by odontoblasts. Phosphophoryns are probably involved in controlling the site and/or the rate of circumpulpal mineralization. Other moderately phosphorylated (MP) and low phosphorylated (LP) proteins have also been detected in dentin, but have not been studied extensively. A 53 kDal dentin sialoprotein (DSP) that resembles bone sialoproteins is expressed by odontoblasts and by pulp cells, but essentially by no other cell type. The function of this protein is unknown. Osteocalcin (bone Gla protein) is synthesized by osteoblasts and by odontoblasts and found in the ECM of bone and dentin. Other tissues or cells (including pulp) do not express osteocalcin. The highly specific nature of these dentin and bone ECM proteins suggests that antibody and molecular probes for the phosphoproteins, DSP and osteocalcin could be valuable in studies on the differentiation and identification of odontoblasts and their precursors. Other bone NCPs shown to be present in dentin may also prove to be important in dentinogenesis. PMID- 1508894 TI - Pulpal vascular changes in inflammation. AB - Changes in pulpal vessels in experimentally induced acute and chronic pulpitis in dog tooth were investigated using corrosive resin casts and scanning electron microscopic examination. Following a cavity preparation without water spray, increased permeability of blood vessels occurred in the primary stage of acute pulpitis. This was evidenced by the extravasation of resin from the vessel. This phenomenon was found initially in the venular network as well as in the capillary network located under the dentin. The morphological change was minimal in the vascular network underneath the cavity. This is in contrast to an expanded and tortuous vascular network representing an ulceration which was found around an abscess in chronic pulpitis. Furthermore, formation of vascular loops and AVAlc close to the inflamed region may represent a protective change in the pulp against inflammation. PMID- 1508895 TI - Effects of selected inflammatory mediators on blood flow and vascular permeability in the dental pulp. AB - One of the major events involving inflammatory processes is the alteration of microcirculatory hemodynamics by inflammatory mediators released from tissue components. Using modern macrocirculatory techniques, 15 mu radioisotope labeled microspheres, 133Xe washout, laser Doppler flowmetry and double isotopes, 125 and 131I-albumin, and microcirculatory methods, intravital fluorescence microscopy with FITC labeled dextran, we have examined the effects of selected mediators, e.g. 5-hydroxytryptamine (5-HT), prostaglandin E2 (PG-E2), bradykinin (BK), substance P (SP), calcitonin gene related peptide (CGRP) and histamine on blood flow and vascular permeability in the pulp of experimental animals. Surprisingly, SP and CGRP caused weak albumin leakage in the pulp, while the opposite is true in high compliance tissues, such as muscles, suggesting that the vessels in a low compliance environment, such as the pulp, may not be as permeable in response to selected mediators. Intraarterial injection of 5-HT caused a strong vasoconstriction which was mediated by 5-HT1p receptor subtype. The pulpal 5-HT receptor subtype was identified by immunocytochemistry, receptor autoradiography and functional investigations. Intravital fluorescence microscopy observations of the rat incisor preparation showed that histamine, BK and PGE2 increased permeability, whereas isoproteranol caused partial inhibition of the BK-induced increase. In an induced pulpal inflammation model using plaque extract, blood flow increased over 40% in the moderately inflamed pulp, which demonstrated severe vasodilation and polymorpholeukocyte accumulation. In the partially necrotic pulp, blood flow decreased nearly 35%. Results of this study clearly show that there is a high structural/functional correlation in pulpal microcirculation in inflammation. As demonstrated in this presentation, the effects of inflammatory mediators on pulpal microcirculatory hemodynamics are complex.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1508896 TI - The role of selected cations in the desensitization of intradental nerves. AB - Dentinal sensitivity is a common complaint of patients. Removal of cementum or enamel leaves the dentin exposed allowing various stimuli to produce fluid movement through the dentinal tubules. These fluid movements are believed to activate pulpal sensory nerves leading to pain. Various therapeutic approaches have been investigated to treat this problem. Resins, fluoride compounds and oxalate solutions have been used to block the dentinal tubules. KNO3 and SrCl2 are active ingredients in desensitizing tooth pastes but neither compound reduces the permeability of dentine. The ability of various solutions to decrease hypertonic (3M NaCl) evoked nerve activity was tested in the canine teeth of anesthetized cats. Excitatory and desensitizing solutions were placed into a deep dentinal cavity prepared over the incisal pulp horn. An electrode used to record nerve activity was also placed into this deep cavity. KNO3 and other K+ ion containing solutions elicit a biphasic effect on nerve activity. Immediately following application of these solutions into the deep dentinal cavity there is a brief burst of high frequency spike activity. Following this brief period of excitation, the intradental nerves are silent and respond weakly to hypertonic NaCl. CaCl2 and other divalent cation solutions also inhibit hypertonic NaCl induced nerve activity, but have a weaker effect than that exerted by K+. These observations can be explained based on the effects of various ions on nerve excitability. Increasing the K+ ion concentration in the vicinity of the dentinal nerve terminal depolarize and activates the nerve fibers. Following a prolonged period of depolarization the action potential mechanism is inactivated. Divalent cation solutions stabilize the nerve membrane without changing the membrane potential. Desensitizing solutions do not decrease nerve activity by an effect on pulpal blood flow. This experimental model does not entirely explain the clinical action of these desensitizing agents. The role of inflammation in hypersensitivity and dental pain is currently being investigated. PMID- 1508897 TI - Tissue pressure and blood flow in pulpal inflammation. AB - The initial vascular reactions during inflammation are vasodilation and increased vessel permeability. Both these basic reactions cause increased pulpal fluid volume. In the dental pulp the inflammatory vascular reactions take place in a rigid enclosed dentin chamber, which to some extent makes the pulp vulnerable. Due to this lack of distensibility any gain in pulpal volume will necessarily increase the pulpal tissue pressure. If the tissue pressure rises to the same level as the blood pressure it will compress the pulpal vessels, thus counteracting a beneficial blood flow increase during inflammation. Using the micropuncture technique and laser Doppler flowmetry we have performed simultaneous measurements of tissue pressure and blood flow in the cat dental pulp during neurogenic inflammation. Sensory nerve stimulation caused a rise both in blood flow and tissue pressure. Our findings thus strongly suggest that the increased pulpal tissue pressure promote fluid absorption back into the blood. If, in theory, plasma proteins and other macromolecules had leaked out during sensory nerve stimulation they must have been successfully removed by lymphatics, unless the tissue pressure would have risen to the same level as the capillary blood pressure causing a fall in PBF. This was not found. On the contrary, increased blood flow was measured, even in experiments lasting for more than 8 hours. It is therefore concluded that the pulp may have a beneficial blood flow increase during inflammation in spite of simultaneously increased tissue pressure. PMID- 1508898 TI - Involvement of sensory nerves in hemodynamic reactions. AB - Small diameter afferent nerves in the pulp contain vasoactive peptides (tachykinins and CGRP) which are released upon nerve stimulation causing long lasting vasodilation. The aim of the present experiments was to study the contribution of afferent nerves in vasodilator reactions in the cat dental pulp when clinical procedures were applied. For this purpose the inferior alveolar nerve (IAN) was cut unilaterally 10 days prior to study. Lower canines were then subjected to various stimuli and blood flow responses in the pulp were monitored by laser Doppler flowmetry. Bipolar electrical tooth stimulation (5 impulses, at 2 Hz, 50 microA) and application of capsaicin (10(-4) M) in a deep cavity instantaneously induced long lasting increases in pulpal blood flow in control teeth but not in denervated teeth. Bradykinin (10(-3) M) applied locally produced a more rapid and larger pulpal vasodilation in innervated than in denervated teeth. Intermittent grinding (3 times, 1 sec each) of surface dentin with a round diamond bur instantly increased flow in control teeth by 53%, whereas in denervated teeth the response was delayed and significantly smaller (16% increase). Deeper preparations produced long lasting responses of similar magnitude on both sides but the onset was much slower in denervated teeth. Percussion and low intensity ultrasonic stimulation (1 sec) instantly caused increased flow in control teeth but not in denervated teeth. The effect was abolished by local anesthetic (mepivacaine) injection apically. Sympathectomy and acute IAN denervation did not alter the responses. The results show that afferent (sensory) nerves contribute importantly to hemodynamic reactions in the pulp in response to clinical procedures. PMID- 1508899 TI - Pathobiology of the tooth microcirculation: a reaction. PMID- 1508900 TI - Colocalization of TGF-beta 1 and extracellular matrix proteins during rat tooth development. AB - Recent studies suggest that TGF-beta 1 controls events in embryogenesis via its modulation of the extracellular matrix (ECM). During tooth development, histomorphogenetic and cytodifferentiation events are regulated by ECM-mediated epithelial-mesenchymal interactions. In this study, we have investigated the in vivo relationship of the localization of TGF-beta 1 to various ECM proteins, including glycosaminoglycans (GAGs), fibronectin, collagens I and III and to the enzyme alkaline phosphatase, at the early and late bell stages of rat molar tooth development. We have used polyclonal antibodies specific to peptides present in the precursor and processed forms of TGF-beta 1, fibronectin and Collagens I and III and immunohistochemical methods of detection. GAGs were stained with Alcian Blue GX and alkaline phosphatase was detected with the enzyme Naphthol-AS B1. Our results indicate that both the intracellular and extracellular forms of TGF-beta 1 are expressed in a site-specific manner, and that the growth factor colocalizes with alkaline phosphatase, fibronectin, collagens I and III and GAGs during the bell stages of tooth development. These data support the hypothesis that in tooth development, the actions of TGF-beta 1 may contribute to important qualitative changes in the composition and structure of extracellular matrices. PMID- 1508901 TI - Characterization of bone resorptive mediators in active periapical lesions. AB - The mechanism of bone destruction in periapical lesions was studied using a rat model system. Periapical lesions were induced by pulp exposure and infection from the oral environment. Lesions expanded most rapidly between induction on day 0 and day 15 ("active phase"), with enlargement occurring at a slower rate thereafter (days 20 and 30, "chronic phase"), as assessed by radiography and automated image analysis. Pooled extracts of day 15 periapical tissues contained significant levels of bone resorbing activity (BRA), as determined by 45Ca release from fetal rat long bones. Normal rat dental pulp and periodontal ligament contained no activity. In kinetic experiments, highest levels of BRA were detected in active phase tissues on days 10 and 15, with BRA declining thereafter in chronic phase tissues to near baseline levels by day 30. In characterization studies, BRA in pooled day 15 tissue extracts was unaffected by treatment with polymyxin B, but was completely abolished by proteinase K treatment or heating to 70 degrees C, indicating an active moiety distinct from bacterial LPS, probably a protein(s). FPLC gel filtration chromatography revealed that BRA could be resolved into four major peaks, of MW 30-60 kD (Peak I); 15-20 kD (II); 1-2 kD (III); less than 1kD (IV), consistent with the presence of the following bone resorptive mediators: (I) cytokines TNF alpha, TNF beta and/or unprocessed IL-1 alpha; (II) processed IL-1 alpha and/or IL-1 beta; (IV) PGE2. These findings demonstrate that bone resorbing activity is temporally related to bone destruction, and that the activity present during the rapid phase of periapical lesion expansion is primarily attributable to bone resorptive cytokines. PMID- 1508902 TI - Pathophysiological roles of arachidonic acid metabolites in rat dental pulp. AB - Arachidonic acid metabolism in normal rat incisor pulp was examined by measuring the conversion activity of exogenously added arachidonic acid in pulpal homogenates. It was demonstrated that the major metabolites were 12 hydroxyeicosatetraenoic acid and prostaglandin (PG) I2. Immunohistochemical studies revealed that PGI2 synthase was distributed in the pulpal blood-vessel cells, fibroblasts and odontoblasts, suggesting that PGI2 may contribute to regulating the function of these cells. When the incisor pulp was experimentally inflamed by applying lipopolysaccharide, arachidonic acid metabolism in the pulp showed overall increase. Change in the pulpal vascular permeability, which was assessed by quantifying the amount of extravasated dye, was almost parallel to the changes in PGE2 and PGI2 production. When production of the PGs was inhibited by indomethacin, the increase of vascular permeability in the inflamed pulp was also suppressed. Topically-applied PGE2 and PGI2 methyl ester abolished the suppression of increase in vascular permeability by indomethacin. These results suggest that PGE2 and PGI2 may be involved in the increase of vascular permeability in the experimental pulp inflammation. We further measured the production of leukotriene (LT) B4 in the inflamed pulp by incubating isolated pulp samples with Ca ionophore A23187, followed by radioimmunoassay. Change in LTB4 production was revealed to be almost parallel to that of neutrophil infiltration. BW755C, an inhibitor of both cyclooxygenase and lipoxygenase, reduced both LTB4 production and neutrophil infiltration. Accordingly, it was suggested that LTB4 may be involved in neutrophil infiltration in the experimental pulp inflammation. PMID- 1508903 TI - Mineral-associated adhesion proteins are linked to root formation. AB - There is a general agreement that the extracellular environment plays a critical role in controlling cell behavior. Thus, significant research efforts have focused on understanding the effects of extracellular matrix proteins on cell function. In particular we have focused on determining the role of adhesion proteins in the regulation of root formation. Using an OPN antibody, 2arN (generously provided by Drs Craig and Denhardt), the expression of OPN during root formation was determined. OPN (osteopontin) is a bone-associated adhesion protein. OPN was expressed in the dental follicle region of molars obtained from 3 day old CD-1 mice, but was not expressed in the odontoblast layer. In contrast by day 8, positive staining was noted in the odontoblast layer, as well as in the area of Hertwig's epithelial root sheath. However, at this same time point no positive labeling for 2arN was observed in the enamel organ or in the dental papillae cells. By day 15 positive staining for OPN was seen in the area of the periodontal ligament, as well as the region of primary deposition of extracellular matrix onto dentin. Also determined was the ability of fibronectin, OPN and dentin sialoprotein (DSP) to promote the attachment of dental ectomesenchymal cells, in vitro. Interestingly, these cells attached remarkable well on bacteriological dishes (control) in the absence of an adhesion protein. DSP did not increase cell attachment beyond that observed for control cells. In contrast, both fibronectin and OPN enhanced cell attachment. These studies, while preliminary indicate that OPN is expressed in a unique fashion during root development, thus suggesting a regulatory role for such adhesion proteins during root formation. PMID- 1508904 TI - The effects of capsaicin on pulpal blood flow. AB - One of the initial events in pulpal inflammation has been characterized as neurogenic inflammation: the release of neuropeptides following excitation of sensory C-fibers by noxious stimuli which alters microcirculatory parameters, that is, vasodilation and plasma extravasation. Thus, the purpose of the study was to investigate the effect of capsaicin on pulpal blood flow (PBF) with the aim of understanding neurogenic inflammation in the dental pulp by characterizing the response of the pulpal vasculature to repeated applications of various concentrations of capsaicin. Experiments were performed on canine teeth of cats anesthetized with sodium pentobarbital. PBF was measured by the laser Doppler flowmeter following the application of capsaicin into the dentinal cavities of the canine teeth. The increases of PBF to capsaicin were 31.8 +/- 6.3% (n = 6) and 54.2 +/- 6.2% (n = 9), for 1 microM and 100 microM capsaicin, respectively. The increase of PBF peaked at about 50 sec after the capsaicin placement and the PBF returned to control level within 20 min following capsaicin removal. Four repeated applications of 1 microM capsaicin caused a small change in the peak PBF amplitude. In contrast, a second application of 100 microM capsaicin caused a significantly smaller increase of PBF than the first application (26.8 +/- 6.4% vs. 54.2 +/- 6.2%). Results of the present study show that local application of capsaicin caused the increase of PBF and that repeated capsaicin stimulations inhibited PBF responses. Smaller PBF increases in response to high concentrations of capsaicin also suggested the depletion of vasoactive substances, e.g. substance P, from the sensory nerve terminals, which appears to be dose dependent. The PBF response to capsaicin suggests that neurogenic inflammation in the dental pulp involves capsaicin-sensitive nerve endings. PMID- 1508905 TI - Temperature related changes in pulpal microcirculation. AB - During dental treatment temperatures can be reached which might possibly damage the tooth pulp. To determine the effect of both thermal stimulation on pulpal microcirculation and local anesthesia on thermoregulation we measured the pulpal blood flow by using laser Doppler flowmetry. Experiments were carried out on lower incisors of Wistar rats anaesthetized with thiopental. The rats were divided into three groups, with one remaining untreated, and the others being either desensitized with capsaicin or sympathectomized with guanethidine. In a range between 33 degrees C and 42 degrees C there was no substantial change in blood flow, which, however, was the case below 33 degrees C. Up to 49 degrees C an increase could be recorded in both untreated and guanethidine pretreated animals, whereas the capsaicin groups showed almost no reaction. This increase in blood flow can be blocked reversibly by local anaesthesia. For this purpose we tested articain 5% and mepivacain 3%, both without constrictor. Intravital microscopic studies show that the temperature related increase in blood flow is also associated with plasma extravasation. From these results we draw the conclusion that pulpal thermoregulation is linked to nociceptive sensory neurons and can be described as "neurogenic inflammation". PMID- 1508906 TI - Changes in pulpal blood flow and in fluid flow through dentine produced by autonomic and sensory nerve stimulation in the cat. AB - We have recorded the flow of fluid through exposed dentine in cat canines. The effects on this flow of electrical stimulation of the cervical sympathetic trunk (CST) and of the inferior alveolar nerve (IAN) were investigated. In some preparations, pulpal blood flow was also monitored with a laser Doppler flow meter and the compound action potentials evoked by IAN stimulation were recorded from the tooth. CST stimulation (0.5-5/s) resulted in a significant decrease in the rate of outward flow of fluid through the dentine or, with the higher frequencies tested, a reversal of the flow. CST stimulation also produced vasoconstriction. IAN stimulation caused a significant increase in the rate of outward flow of fluid from the dentine. This effect required the recruitment of A delta fibres: A beta fibres alone had no effect. Pulpal vasodilatation occurred with the same threshold. Mechanical stimulation of dentine in an acutely denervated tooth also caused vasodilatation, indicating that pulpal afferents were involved. The results show that the rate of fluid flow through dentine, and hence the rate of inward diffusion of chemicals from the oral cavity, can be influenced by changes in the state of the pulpal microvasculature. PMID- 1508907 TI - Effects of inflammation on dental sensory nerves and vice versa. AB - A brief review of the normal sensory innervation of teeth is presented, especially concerning the fibers that are immunoreactive (IR) for calcitonin gene related peptide (CGRP). Numerous CGRP-IR fibers innervate coronal dentin at sites populated by primary odontoblasts and associated pulp cells that synthesize nerve growth factor (NGF). If the primary odontoblasts and adjacent pulp cells are lost as a consequence of injury, CGRP-IR dentinal innervation is greatly reduced. The responses of CGRP-IR nerve fibers to pulpal injury are reviewed. Those reactions show that pulpal sensory nerve fibers can alter the size, shape and immunoreactivity of their terminal branches in response to different stages of inflammation and healing. PMID- 1508908 TI - Role of intradental A- and C-type nerve fibres in dental pain mechanisms. AB - The arousal of the two components of pain (the first rapid or sharp pain and the second dull pain) are considered to be related to activation of A delta- and C type nociceptive primary afferents, respectively. The same dichotomy of pain sensations may also exist in teeth, although due to the short distance between the site of stimulation and the brain the two sensations might not be as clearly separated as in stimulation of, for example, the extremities. The sensations evoked by stimulation of human teeth vary according to the type of the stimuli applied. Low-intensity electrical stimulation is able to induce non-painful (prepain) sensations. At high current intensities pain is evoked. Drilling, probing and air-drying of exposed dentin induce only pain. Most studies also indicate that thermal stimulation only induces painful sensations. The quality of dental pain can vary. Typically, dentinal stimulation of teeth with healthy pulps induces sharp pain. On the other hand intense heat stimulation can result in dull pain which radiates to a wider area of the face and jaws. This component of the stimulus-induced pain seems to share some characteristics of toothache associated with painful pulpitis. Single fibre recordings of intradental nerve activity in experimental animals have shown that in addition to A-fibres a considerable number of C-type primary afferents innervate the dental pulp. This is in accordance with the results of neuroanatomical studies, which indicate that 70 80% of pulpal axons in human, monkey, dog, and cat teeth are unmyelinated. Intradental A- and C-fibre groups seem to be functionally different and can be activated separately by certain external stimuli. Comparison of the response characteristics of the pulp nerve fibres and the sensations induced from human teeth indicate that: 1) A-fibres are responsible for the sensitivity of dentine and thus for the mediation of the sharp pain induced by dentinal stimulation, 2) Prepain sensations induced by electrical stimulation result from activation of the lowest threshold A-fibres some of which can be classified as A beta-fibres according to their conduction velocities. Comparison of the responses of the A beta- and A delta-fibres indicate that they belong to the same functional group, 3) Intradental C-fibres are activated only if the external stimuli reach the pulp proper. Their activation may contribute to the dull pain induced by intense thermal stimulation of the tooth and to that associated with pulpal inflammation. PMID- 1508909 TI - Sensory physiology: a reaction. PMID- 1508910 TI - Studies on the presence and functional properties of afferent C-fibers in the cat's dental pulp. AB - The present investigation describes how intradental afferent C-fibers can be identified and characterized in the anaesthetized cat. Functional single fibers innervating the lower canine tooth were recorded from filaments split from the inferior alveolar nerve. Fibers responding to monopolar electrical stimulation of the tooth were classified as slowly and fast conducting according to their conduction velocity (c.v.). The axonal c.v. was determined for 31 slowly conducting fibers by electrical stimulation of the nerve. Sixty-eight percent of these proved to be C-fibers. The slowly conducting fibers had higher activation thresholds, smaller amplitudes and longer durations of the action potentials than the fast conducting fibers. Many of the fast but none of the slowly conducting fibers were repetitively activated by a single stimulus pulse. The highest frequency at which the fibers responded to every stimulus pulse was much lower for the slowly than for the fast conducting fibers. Most of the slowly conducting intradental fibers tested were activated by both hot and cold stimulation of the tooth, by pressure applied to the pulp chamber and by the application of KCl or bradykinin to the pulp. Eight C-fibers responded to mechanical stimulation of the pulp. For some fibers the response magnitude correlated with the stimulus intensity. Many slowly conducting intradental fibers developed an ongoing discharge after heat and pressure stimulation. The results indicate that there exists in the dental pulp of the cat afferent C-fibers that resemble polymodal C nociceptors. They might be involved in the generation of the dull aching pain present in inflammatory conditions of the pulp. The activation of intradental C fibers in pulpitis might result either from the elevated pressure and/or by sensitization of the C-fiber endings by inflammatory substances released. PMID- 1508911 TI - Immunoassay evidence for a role of nerve growth factor in development of dental innervation. AB - Nerve growth factor (NGF) is known to have an essential role in prenatal development of spinal and trigeminal primary sensory neurons serving nociceptive functions. Investigation of a possible function of NGF in development of intradental innervation has recently begun with the demonstration by others of NGF mRNA and NGF receptor in the pulp. The pulp is of special interest in this respect because of its late development and unusual properties of its innervation. In the present study, use of a sensitive ELISA for NGF has made it possible to detect and measure NGF antigen in pulps of developing rat molars. Pulps contained relatively high concentrations of NGF before and during the time of innervation development. PMID- 1508912 TI - Immediate physiological response of odontoblasts. AB - The normal structure and function of the odontoblast cell layer is often perturbed by a variety of pathological processes as well as by the restorative procedures and materials required to treat them. It is well accepted and documented that a number of acute histological changes may take place under these circumstances resulting in the loss of integrity of the odontoblast cell layer. To date, our understanding of the immediate physiological response of the odontoblast to pathological processes or iatrogenic trauma remains limited. This paper reviews: first, the evidence for and against the existence of physiological barrier between the distal segments of odontoblast cell bodies; second, the alteration of this physiological barrier following routine restorative procedures; third, the role junctional complexes may play in this barrier function, and finally, the role that dental innervation, both afferent and efferent, may play in influencing and regulating the response of the dental pulp to external stimuli. PMID- 1508914 TI - Patterns and plasticity of dental afferent inputs to trigeminal (V) brainstem neurons in kittens. AB - In the young cat, the natural replacement of deciduous teeth with a permanent dentition may be accompanied by extensive peripheral nerve degeneration and reinnervation. Since we have previously reported significant physiological effects of tooth pulp deafferentation on V brainstem neurons, we wished to determine if deafferentation associated with deciduous tooth exfoliation was accompanied by comparable neuroplastic changes in the brainstem of kittens. We have examined the pulpal afferent terminating pattern within the brainstem as well as the electrophysiological properties of V brainstem neurons during this naturally occurring deafferentation phenomenon. The pattern of the HRP-labelled terminals in different parts of V brainstem subnuclei in kittens was similar to that in adult cats. The highest density of labelled terminals was found in the subnucleus oralis. The properties of subnucleus oralis neurons also showed many similarities between kittens at age of 3-4 months old and adult cats, e.g., (1) in the proportions of neurons activated by tactile stimulation of 1-4 teeth (mandibular and maxillary canines and premolars), (2) the ratio of neurons showing fast adapting or slow adapting responses to dental tactile stimulation, (3) the proportions of neurons activated by electrical pulp stimulation of 1-4 teeth, and (4) the minimal latencies of pulp-evoked responses. However, the incidences of pulpal inputs as well as the convergent pattern to oralis neurons of afferent inputs evoked by periodontal stimulation and electrical pulpal stimulation were less common in kittens than adult cats. PMID- 1508913 TI - Increase in c-fos-like immunoreactivity in the trigeminal nucleus complex after dental treatment. AB - An immunohistochemical study was made of the temporal changes in the expression of the c-fos oncogene protein in the spinal trigeminal nucleus complex (STNC) after three different types of dental injury. One hour after tooth extraction or pulp exposure, c-fos neurons appeared in the ipsilateral subnucleus caudalis, but there were very few c-fos neurons in the ipsilateral subnuclei oralis and interpolaris, and in the trigeminal main sensory nucleus and contralateral STNC. The great number of c-fos neurons was found 2-4 hours after injury, levels decreased by 8 hours after injury. Twenty-four hours after injury, the number of these neurons in subnucleus caudalis became very small. Shallow cavity preparation, however, did not induce an increase in the number of c-fos neurons at any selected postoperative time in STNC. These results indicate that c-fos neurons appear mainly in subnucleus caudalis very soon after severe dental injury. PMID- 1508915 TI - Functional alterations in pulpal microcirculation in response to various dental procedures and materials. AB - Using the quantitative 15 microns microsphere injection method, the effects of several restorative procedures on pulpal microcirculation in dog canine teeth were investigated. Pulpal blood flow (PBF) decreased steadily as the remaining dentin thickness (RD) became smaller with crown preparation without water spray. One hour after the preparation wit 1/3 RD (approximately 1 mm) PBF was reduced to 10% of the control, indicating that dry deep preparation has a deleterious effect on PBF. A careful preparation to an RD of 1 mm under copious water spray had a negligible effect on PBF. Dry preparation to an RD of more than 50%, on the other hand, caused a significant increase in blood flow through shunt vessels, AVAs and "U"-turn loops as determined with the 9 microns and 15 microns microspheres. These shunt vessel activities were especially prominent in the apical portion of the pulp, suggesting that the activation of the shunt vessels may be one of the compensatory mechanisms of the pulp in response to inflammation. In rat incisor teeth observed by intravital microscope, shunt vessels opened up as the incisor tips were drilled. Impression procedures after tooth preparation with water spray using the copper band with wax caused severe flow fluctuation as compared to rubber base material impression. In anesthetics, the use of epinephrine was found to be the single most important factor affecting pulp circulation. Whether it is by infiltration or mandibular block, the use of epinephrine containing anesthetic caused a severe reduction in PBF.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1508916 TI - Etiology of dentin hypersensitivity. AB - Hypersensitive dentin appears to be mainly the result of an activation of the dentinal pain fibres, the A-fibres, at the pulpal wall. The stimuli which activate these nerves are primarily those which remove fluid from the dentinal tubules and mobilize capillary forces, causing a rapid outward flow. Application of a cold stimulus causes the fluid to contract, resulting in a similar rapid outward flow in the pulpal region of the tubules. Hypersensitivity to cold is also marked when there is a fluid-filled gap containing bacteria in the tooth. Experiments have shown that a freshly exposed dentin surface with patent tubules is more sensitive than a surface contaminated by a smear layer. Inflammation in the adjacent pulpal region can also increase sensitivity. The development of hypersensitive cervical and occlusal surfaces is due to mechanical and acidic effects from the oral environment, toothbrush abrasion, erosive components in the diet, plaque and bacterial invasion of dentin. Sometimes dentin is exposed by restorative therapy and occasionally eccentric occlusal loads can contribute to hypersensitivity. The sensitivity may persist unless the open tubular apertures are sealed. PMID- 1508918 TI - Microleakage related to restorative procedures. AB - A current Med-line search from 1966 to present cited over 344 juried publications employing the term microleakage. Dentistry recognizes microleakage as a multifaceted biological phenomenon. Brannstrom et al. (1967), Trowbridge (1982), Narhi (1983), and others have reported the sensory component of microleakage as a consequence of hydrodynamic fluid movement within the dentinal tubule complex. This movement of dentinal fluid has been demonstrated to displace nociceptive receptors which stimulate the nerves of the Group A fibers which run and terminate within the odontoblastic layer (see Matthews 1992). Penetration of oral fluids, bacteria and their toxic products within the preparation-material interface following material insertion accounts for the pathological component of microleakage (Browne and Tobias 1986). Continued microleakage of bacterial infiltrates eventually present as an inflammatory process which may initially signal the dentin complex to respond by deposition of a hypermineralized or sclerotic dentin. The pulp-dentin interface will repair with a specialized zone of reparative dentin. An overwhelming carious lesion often results in pulp infection and eventual necrosis. Vital dentin is an extension of the pulp, presenting the first line of defense to the consequences of microleakage. Recent publications have demonstrated that microleakage of dental materials in non exposed and exposed pulps is a function of controlling bacterial infection. In an exposed mature dental pulp, the mesenchymal tissue permits the reorganization of pulp tissue and regeneration of a new dentin bridge in the presence of a biological seal. New odontoblastoid cells appear to regenerate from deeper pulpoblasts in the presence of various dental materials, apparently without an epithelial stimulating factor (Yamamura 1985). This inherent healing of the dental pulp and regeneration of a new dentin bridge is expressed in the presence of various dental materials, but only in the absence of bacterial infection. Data which evaluates the biological deposition of reparative and dentin bridges as either repair or regeneration are presented as a basis for considering the clinical selections of dental materials. Recent data demonstrate that dentin and pulp healing are ensured when a proper biological seal is provided to control and prevent microleakage. PMID- 1508917 TI - Reactions of sensory nerves to dental restorative procedures. AB - The reactions of sensory nerves to restorative procedures can be classified as immediate, early and late. For each of these, the neural response depends upon the severity of pulpal injury and the stages of inflammation and healing. Immediate responses in the first few minutes include destruction of nerve fibers in the injured dentin and pulp, hypersensitivity of surviving fibers, release of neuropeptides into the pulp and neurogenic inflammation. Early responses occur during the first few days after cavity preparation, with nerve fibers sprouting in the surviving pulp and gaining increased axonal transport and neuropeptide contents. Sensory fibers containing calcitonin gene related peptide (CGRP) greatly outnumber those with substance P (SP); but both types grow toward the surviving odontoblasts and associated pulp tissue surrounding the lesion. Later during subsequent weeks the nerve fibers accompany granulation tissue as it replaces acute inflammation; and nerve sprouting subsides when inflammation is reduced and when reparative dentin covers the injury site. An important response to tooth injury that may regulate nerve sprouting reactions is the increased production of nerve growth factor (NGF) by pulpal fibroblasts near the lesion. The timing of the nerve sprouting reactions suggests that they may contribute to tooth hypersensitivity after restorative procedures. PMID- 1508919 TI - Gastrointestinal satiety in animals other than man. PMID- 1508920 TI - Nutrition information and training: networking in international community nutrition. PMID- 1508921 TI - Can nutritional indicators be used to measure economic development? PMID- 1508922 TI - Integration of human and animal concepts of energy metabolism. AB - With relatively few limitations, findings derived from the study of the energetics of farm animals provide extremely valuable information in the application of human energetics to the solution of dietary questions. The nature of the body's response to variation in energy intake and the nature of variation among individuals are good examples. It is important to appreciate the differences in the usual experimental constraints of studies with animals and humans. Human requirements are based on the summation of the energy costs of several different activities performed throughout the day whereas animal requirements are based on steady-state conditions at various production levels. Although the factors which influence specific biochemical or physiological events may be very similar, the manner in which those effects are incorporated into energy systems and the terminology used to describe them may differ substantially. PMID- 1508923 TI - Approaches and limitations to the prediction of energy requirements in wild animal husbandry and veterinary care. PMID- 1508924 TI - Merits of empirical and mechanistic approaches to the study of energy metabolism. PMID- 1508925 TI - Metabolic aspects of satiety. PMID- 1508926 TI - Integration of internal and external signals in intake control. PMID- 1508927 TI - Dietary reference values. PMID- 1508928 TI - Are there conflicts in dietary advice for prevention of different diseases? PMID- 1508929 TI - Dietary advice: foods or nutrients. PMID- 1508930 TI - Nutritional information: do we know what we are eating? PMID- 1508931 TI - Is our dietary advice effective? PMID- 1508932 TI - Role of gastrointestinal factors in hunger and satiety in man. AB - There is, we feel, a strong case to be made for a major influence of gastrointestinal factors in the control of eating behaviour in humans. Moreover, the findings suggest that satiety and hunger are controlled by different gastrointestinal mechanisms. Gastric distension is perhaps the most important factor that stops people eating, but a true feeling of satiety also requires the presence of nutrients in the small intestine. Hunger appears to be little influenced by the amount of food in the stomach and appears to be more dependent on the nutrient load in the small intestine. I do not mean by this to suggest that the gastrointestinal mechanisms are the only mechanisms controlling eating behaviour in humans or even the most important. Nevertheless they constitute an important and fundamental control system that links with the post-absorptive mechanisms and a plethora of social and conditioning factors to influence what we eat. PMID- 1508933 TI - Nutrition and health development--lessons from Kerala. PMID- 1508934 TI - Nutrition and socio-economic development in Southeast Asia. AB - While most Third World countries, particularly in Africa and Latin America, have experienced a deterioration in child welfare as a result of the severe economic downturn in the 1980s, Southeast Asia in general managed to sustain improvements in the situation of its children because it has maintained satisfactory rates of economic growth. However, there were exceptions within Southeast Asia. The Philippines, Vietnam, Dem. Kampuchea and Laos had unsatisfactory growth rates and, consequently, unsustained nutritional gains from the 1970s through the 1980s. Economic factors exerted a big impact on the Philippine nutrition situation, particularly on the dietary status of the households and the nutritional status of children. As a result of the economic dislocation occurring in the country, the nutritional gains of 1978-82 were not maintained in succeeding years. Unlike the case of Thailand, it has been estimated that the solution to nutritional problems in the Philippines is far from being achieved in the immediate future (Villavieja et al. 1989). On the other hand, the nutrition improvements in Thailand have been as remarkable as the economic growth over the last decade. Long-term investments in health, nutrition and other social services in Thailand (as well as in Indonesia) have paid off according to the assessment by the United Nations (1990). It appears, therefore, that the nutrition situation in developing countries is highly dependent on the economic situation, globally and nationally (Cornia et al. 1987), as well as on investment in social services. Adjustment policies should, therefore, consider their implications on distribution and poverty in order that they could positively contribute to the improvement of the nutrition of the people. PMID- 1508935 TI - Polyclonality of the cytotoxic T lymphocyte response to virus infection. PMID- 1508937 TI - Effects of stearic acid and beef tallow on iron utilization by the rat. AB - Two experiments were done in which anemic rats were fed diets containing safflower oil or stearic acid and low (10 ppm) or adequate (39-42 ppm) iron. Diets were 24% fat by weight. In the stearic acid diets, 2% (Experiment 1) or 4% (Experiment 2) of the fat was supplied by safflower oil to satisfy essential fatty acid requirements. Repletion of hemoglobin, hematocrit, and liver iron was assessed. Compared with safflower oil in both experiments, stearic acid had a significant positive effect (P less than 0.0001) on repletion of hemoglobin (Hb), hematocrit (Hct), and liver iron concentration; the effect on Hb and Hct was most pronounced when dietary iron was low. When expressed as g Hb/mg Fe intake, Hb repletion was affected by a significant interaction between fat and Fe (P less than 0.002) and was greatest in rats fed low iron stearic acid diets. In a third experiment, rats were fed low dietary iron and 24% safflower oil, 20% stearic acid + 4% safflower oil, 3.2% stearic acid + 20.8% safflower oil, or 20% beef tallow + 4% safflower oil. The 20% beef tallow provided 3.2% stearic acid in the total diet. The response of Hb and Hct were similar to those in the first two experiments for rats fed safflower oil or stearic acid. Rats fed beef tallow had significantly greater (P less than 0.05) Hb and Hct repletion than did rats fed safflower oil, although the degree of repletion was less than that observed in rats fed 20% stearic acid. There was no difference in iron repletion of rats fed 3.2% stearic acid and rats fed beef tallow. We conclude that stearic acid enhances iron utilization by rats. PMID- 1508936 TI - Eicosapentaenoic acid inhibits endothelium-dependent relaxation to acetylcholine in guinea pig coronary resistance vessels. AB - Dietary supplementation with eicosapentaenoic acid (EPA) alters arachidonate metabolism. This study characterizes the effect of dietary EPA on endothelium dependent vasodilation to acetylcholine (ACH) and ATP in guinea pig coronary resistance vessels. Guinea pigs were fed standard chow (n = 6), standard chow+sesame seed oil (n = 6), or standard chow+menhaden fish oil (17% EPA; n = 6). Coronary vasodilations were examined in the isolated, potassium-arrested heart utilizing a modified Langendorff preparation. Coronary vessels were constricted with prostaglandin F2 alpha and relaxed with ACH (5.5 x 10(-9)-10(-6) moles) or ATP (10(-10)-10(-7) moles). Endothelium-dependent dilations to ACH, but not ATP, were attenuated by dietary supplementation with EPA. To assess the role of the endothelium in modulating vascular responses to agonists following dietary manipulation, the perfusate was stimulated by electrolysis (9 V, 4 Hz, 2 msec) in order to generate free radicals, which we have shown to preferentially damage the endothelium. After endothelial damage, responses to ACH, ATP, and nitroprusside were similar between the dietary groups. In an additional group of standard diet animals (n = 6) experiments were performed to assess the role of prostanoid metabolism in affecting coronary vascular reactivity. Perfusion of hearts with indomethacin (14 microM) reduced endothelium-dependent vasodilations to ACH (5.5 x 10(-9)-10(-6) moles), but not to ATP (10(-10)-10(-7) moles). After endothelial damage, infusion of ACH resulted in vasoconstriction, whereas vasodilation responses to ATP were absent. We conclude that dietary supplementation with EPA inhibits endothelium-dependent dilations to ACH in guinea pig coronary microvessels. These diet-related differences in vascular reactivity may be related to the fish-oil-induced alteration of vasodilator prostaglandin metabolism. In the coronary bed, different endothelial factors appear to mediate relaxation to ACH and ATP. PMID- 1508938 TI - Effects of H-2 on neural tube defects in congenic mice. AB - Pregnant mice congenic with C57BL/10 (B10.A, B10.BR, B10.D2, B10.A[2R], B10.A[5R], B10.A[15Rd, B10.A[1R], B10.A[18R], and B10.0L) were fed Purina Mouse Chow or the same diet plus 200 IU of vitamin A daily. The pregnant dams were sacrificed on the eighteenth day of gestation, and the fetuses were sexed and examined for defects in neural tube development. The frequency of neural tube defects was low (mean frequency of all strains, 0.36%) and was not affected by the addition of vitamin A (200 IU/day) to the diet. Twenty-seven of the 29 defects observed occurred in the anterior tube (exencephaly); fourteen were identified in female fetuses, but the sex could not be determined in the other 15 cases because of fetal death and early autolysis. Variations in frequency among the strains suggest that a locus between E beta and H-2D has a moderate influence on the occurrence of neural tube defects. Strains that had H-2d alleles in this segment of the H-2 complex had relatively high frequencies, and those with H-2b or H-2k alleles had significantly lower frequencies. PMID- 1508940 TI - Effects of cold acclimation and fasting on thyroxine 5'-deiodinase in brown adipose tissue of ob/ob mice. AB - Gradual acclimation to mild cold for 6 weeks increases the total activity of thyroxine 5'-deiodinase in brown adipose tissue (BAT) of genetically obese (ob/ob) mice to a level greater than that in similarly acclimated lean mice. This increase is largely due to the growth of the BAT in the ob/ob mouse, because specific activity of the enzyme is only slightly increased. In similarly cold acclimated lean mice, the specific activity of thyroxine 5'-deiodinase was not altered. BAT mitochondrial GDP binding increased to the same high level in the gradually cold-acclimated ob/ob mouse as in cold-acclimated lean mice. We conclude that the growth and maintenance of BAT in the cold-acclimated ob/ob mouse, as in the cold-acclimated lean mouse, does not require greatly increased activity of thyroxine 5'-deiodinase. Fasting for 48 hr did not alter thyroxine 5' deiodinase activity of BAT in either lean or ob/ob mice. The fasting-induced increase in activity seen by others in lean mice is probably due to thermoregulatory stimulation of BAT occasioned by the low environmental temperature at which the fasting occurred. PMID- 1508939 TI - Role of extracellular magnesium in insulin secretion from rat insulinoma cells. AB - Magnesium (Mg2+) is an abundant intracellular cation that participates in the regulation of the intracellular concentration of ATP. In this study, we examined the relationship between insulin secretion and intracellular free Mg2+ ([Mg2+]i) in a rat-insulinoma cell line (RIN m5F), using a fluorescent dye (Mag-fura-2). KCI, forskolin, and D-glyceraldehyde increased [Mg2+]i and insulin secretion from RIN m5F cells in a dose-dependent fashion. Verapamil, a voltage-dependent Ca2+ channel blocker, inhibited the increase of [Mg2+]i that was evoked by KCI, forskolin, and D-glyceraldehyde. In a Mg(2+)-free buffer, these agents failed to cause an elevation in [Mg2+]i; however, the insulin response to KCI and forskolin was enhanced, compared with that in the presence of Mg2+ (1.25 mM). Our findings suggest that [Mg2+]i is dependent upon extracellular Mg2+, and the influx through the voltage-dependent Ca2+ channel. Mg2+ may competitively inhibit the voltage dependent Ca2+ channel, which is known to play a role in insulin secretion. An absence of Mg2+ in the extracellular space may result in enhanced insulin secretion. [Mg2+]i may play a role in insulin secretion from RIN m5F cells. PMID- 1508941 TI - Temporal effects of estradiol and diethylstilbestrol on pituitary and plasma prolactin levels in ovariectomized Fischer 344 and Holtzman rats: a comparison of radioimmunoassay and Nb2 lymphoma cell bioassay. AB - An Nb2 lymphoma cell bioassay (Nb2BA) and a radioimmunoassay (RIA) were used to compare plasma and pituitary levels of prolactin in ovariectomized Fischer 344 (F344) and Holtzman rats treated with either diethylstilbestrol (DES) or estradiol for up to 8 weeks. The objectives were to determine whether there were temporal differences in prolactin responses in strains with different genetic predispositions to estrogen-induced pituitary tumor formation and to determine whether the results of the two assay methods were equivalent. All rats were ovariectomized for 7 days and all except controls received subcutaneous Silastic implants of DES or 17 beta-estradiol and were sacrificed at intervals from 2 days to 8 weeks later. Pituitary content and plasma levels of prolactin were determined by Nb2BA and RIA and the ratio of these measurements was calculated. DES induced a significant increase in pituitary prolactin in F344 rats by 2 days of treatment, as measured by RIA. Pituitary content increased to a peak by Day 4, after which a gradual decline occurred until the end of the experiment. Nb2BA measurements were similar to those obtained by RIA, except at 8 weeks, when the content determined by Nb2BA was significantly higher than the content determined by RIA. When estradiol was given to F344 rats a pattern of increase and subsequent decrease in pituitary content similar to that seen with DES was observed and levels measured by Nb2BA and RIA were essentially equivalent. Plasma levels of prolactin in DES-treated F344 rats increased exponentially through the 8 weeks, and the Nb2BA measurements were significantly greater than levels determined by RIA throughout the treatment period. Estradiol treatment produced a pattern of change in plasma levels of prolactin similar to that observed with DES, except that RIA and Nb2BA measurements were not different. Comparable results were obtained in Holtzman rats, except plasma levels were not increased to the same degree as seen in F344 rats. From these results, we conclude that DES, but not estradiol, can selectively increase the secretion of prolactin that is more bioactive than immunoreactive and that this effect of DES is observed in F344 and Holtzman rats, although F344 rats released more prolactin in response to estrogens than did Holtzman females. PMID- 1508943 TI - Naloxone reversal of ischemic arrhythmia is stereospecific and suggests role of endogenous opioid peptides in ischemic heart disease. AB - The effects of the stereoisomers of naloxone during myocardial ischemia were studied. (-)-Naloxone (but not the (+)-isomer naloxone) attenuated the ischemia induced cardiac arrhythmias, hypotension, and bradycardia that result from coronary artery occlusion in anesthetized rats. From these findings, it may be inferred that endogenous opioid peptides may play a role in the pathophysiology of myocardial ischemia. It is also suggested that naloxone may have therapeutic value in the prevention and treatment of ischemic heart disease. PMID- 1508942 TI - Interleukin 1 pretreatment reduces the insulin response to glucose in chronic sucrose-fed rats. AB - The present studies were undertaken to determine whether interleukin 1 beta ([IL 1] 1.0 micrograms/kg, ip) pretreatment for 3 days impairs the adaptive response to sucrose feeding in rats. One week after the last IL-1 injection, when no differences in plasma glucose and serum immunoreactive insulin (IRI) levels were observed, sucrose feeding was started. Sucrose feeding for 4 weeks did not affect basal glucose levels, whereas basal IRI levels were increased in sucrose-fed rats without IL-1 pretreatment. Eight weeks later, plasma glucose levels were increased before and at 15 min after intravenous bolus of 0.5 g/kg of glucose in sucrose-fed rats with IL-1 pretreatment. Only in IL-1-treated sucrose-fed rats were basal and glucose-stimulated IRI levels significantly reduced, compared with those levels in sucrose-fed vehicle-treated rats. IL-1 decreased pancreatic IRI contents at 1 and 9 weeks after the injection. These data suggest that pancreatic damage by IL-1 attenuated insulin response to glucose stimulation after long-term sucrose feeding. PMID- 1508944 TI - Iron metabolism is modified by the copper status of a human erythroleukemic (K562) cell line. AB - Copper deficiency is known to result in a microcytic, hypochromic anemia. Red cells of copper-deficient animals have less hemoglobin than their copper-adequate counterparts. The objective of this work was to determine what role copper plays in maintaining hemoglobin levels. It was hypothesized that the primary defect lies in intracellular iron metabolism. The influence of copper supplementation on iron uptake and storage was examined in a cell line capable of hemoglobin synthesis. The results demonstrated that copper supplementation of human K562 cells was associated with higher cytosolic iron levels and ferritin levels. Copper supplementation of the cell culture altered the initial rate of iron uptake from transferrin and enhanced iron uptake in noninduced cells; however, in hemin-induced K562 cells, which express fewer transferrin receptors on the cell surface, copper appeared to reduce iron uptake. Subsequent studies showed that the cells were able to take up the same amount of iron from transferrin when incubated over a longer period of time (24 hr). In the noninduced (non-hemoglobin synthesizing) cells, proportionally more iron was associated with the ferritin. We concluded from these studies that copper affects both uptake and storage of iron and that copper supplementation reduces cellular iron turnover. PMID- 1508945 TI - Regulation of duodenal insulin-like growth factor I and active calcium transport by ovariectomy in female rats. AB - There is a significant body of data that supports the concept that reproductive hormones in females have effects on duodenal calcium transport that are not mediated via altered circulating concentrations of 1,25-dihydroxyvitamin D (1,25(OH)2D). Previously, we have shown parallel alterations in duodenal Ca transport and longitudinal bone growth rate in sexually maturing female rats in response to ovariectomy and estradiol (E) treatment of ovariectomized (OVX) rats (OVX+E) without any change in circulating levels of 1,25(OH)2D or parathyroid hormone. Results are presented here from experiments designed to: (i) further explore the relationship between 1,25(OH)2D and ovarian status in the regulation of duodenal calcium transport, and (ii) determine whether OVX and E replacement alter circulating and duodenal levels of insulin-like growth factor I (IGF-I) that might be related to effects on Ca transport. Growth hormone, which has been shown to affect intestinal Ca absorption and vitamin D metabolism, is thought to act indirectly by stimulating IGF-I. Six-week-old female rats were OVX, given estradiol implants (OVX+E), and fed a diet containing either 0.5% or 0.1% Ca for 3 weeks. In both diet groups, the OVX animals exhibited a higher level of Ca transport, as measured by the everted gut sac method, than either the intact controls or the OVX+E group; there was no difference in calcium transport between the different diet groups. Although there was no difference in circulating levels of 1,25(OH)2D among the intact, OVX, and OVX+E groups fed either diet, animals fed the 0.1% Ca diet had higher circulating levels of 1,25(OH)2D than those fed the 0.5% Ca diet. There was no difference in duodenal levels of calbindin9K among intact, OVX, and OVX+E animals in either diet group, although the animals fed the 0.1% Ca diet had higher levels of calbindin9K than the animals fed the 0.5% Ca diet. In animals fed the 0.5% Ca diet, OVX resulted in elevated serum and duodenal levels of IGF-1, as compared with intact and OVX+E animals on the same diet. In animals fed the 0.1% Ca diet, there was no elevation of IGF-I in the OVX group relative to intact and OVX+E animals. These results lend additional support to the concept that alterations in duodenal active calcium transport that occur with alterations in ovarian hormones are not mediated by changes in serum levels of 1,25(OH)2D, but may be related to some factor related to growth, possibly IGF I. PMID- 1508946 TI - Testosterone alters duodenal calcium transport and longitudinal bone growth rate in parallel in the male rat. AB - Duodenal active calcium transport and longitudinal bone growth rate have been shown previously to be regulated in parallel by alteration of gonadal hormone status in sexually maturing female rats. The present study was designed to extend these observations to the sexually maturing male rat. Male rats were orchidectomized (ORX) and given Silastic implants containing either testosterone or estradiol at 6 weeks of age. At 9 weeks of age, duodenal active calcium transport was measured by the everted gut sac method and longitudinal bone growth rate was determined by tetracycline labeling. Decreases in body weight, longitudinal bone growth rate, duodenal calcium transport, and serum Ca and P were exhibited by ORX animals as compared with age-matched control animals. Testosterone administration to ORX animals resulted in an increase in body weight, longitudinal bone growth rate, duodenal calcium transport, and serum Ca and P as compared with ORX animals to a level not significantly different from that of age-matched control animals. Estradiol administration to ORX animals resulted in an additional decrease in body weight, although no significant effect on duodenal calcium transport, serum Ca, or P was noted as compared with ORX animals. There were no statistically significant alterations in the circulating levels of 1,25-dihydroxyvitamin D, parathyroid hormone, or osteocalcin in response to any of the experimental manipulations of gonadal status. These results indicate that, as in the female, gonadal hormone status affects intestinal calcium transport in sexually maturing male rats in parallel with changes in bone growth rate by mechanisms that are independent of circulating levels of 1,25-dihydroxyvitamin D. PMID- 1508947 TI - Decentralization of the superior cervical ganglia and the immediate hypersensitivity response. AB - Bilateral decentralization of the superior cervical ganglia protects against pulmonary inflammation when measured 8 hr after induction of anaphylaxis in rats sensitized to the nematode, Nippostrongylus brasiliensis. Since anaphylactic shock produces immediate perturbations to the cardiovascular and respiratory systems, we examined whether bilateral decentralization of the superior cervical ganglia modified the responses of these two systems during the first 4 hr of the anaphylactic response. With the exception of the bronchioles, decentralization did not protect against anaphylaxis-associated increases in extravasation of albumin, and the small changes in respiratory function induced by anaphylaxis were unaffected by the denervation. Decentralization did not alter anaphylaxis induced reductions in blood flow to the gastrointestinal tract; however, blood flow to the kidneys and spleen of decentralized rats was restored more rapidly to normal values. These results suggest that the protective effect of decentralization on the late phase pulmonary inflammation of anaphylaxis is unrelated to early changes in respiratory mechanics, although the protection may be facilitated by the more rapid re-establishment of normal cardiovascular homeostasis. PMID- 1508949 TI - Monthly prostaglandin bibliography prepared by University of Sheffield Biomedical Information Service. PMID- 1508948 TI - Phosphatidylserine suppresses antigen-specific IgM production by mice orally administered sheep red blood cells. AB - Phosphatidylserine is an endogenous acidic phospholipid that has been shown to modulate nervous system function. In the immune system, phosphatidylserine has been shown to suppress T dependent and T independent immune responses after systemic administration of antigen and lipid. However, no studies on the possible regulation by phosphatidylserine on mucosal immunity have been undertaken. Therefore, we studied the action of phosphatidylserine on immunocompetence using orally immunized mice. Mice orally administered phosphatidylserine (25 mg/kg/day) and subsequently intubated intragastrically with sheep red blood cells showed a significant decrease in antigen-specific IgM production by splenic lymphocytes compared with controls. Furthermore, the response of splenic lymphocytes obtained from phosphatidylserine-treated, antigen-primed animals to antigen or pokeweed mitogen in proliferation assays was markedly suppressed, compared with splenic lymphocytes obtained from nontreated, antigen-primed mice. Similarly, splenic lymphocytes from phosphatidylserine-treated, antigen-primed animals cultured in the presence of antigen produced no measurable interleukin 4 and low levels of interleukin 2, whereas splenic lymphocytes from antigen-primed animals produced measurable levels of interleukin 4 and significantly higher levels of interleukin 2. By fluorescence-activated cell sorter analysis, brightly stained B lymphocytes (Ig+) take up a larger portion of phosphatidylserine than do brightly stained T lymphocytes (Thy 1.2+). Collectively, these results point to the immunosuppressive qualities of phosphatidylserine. Given that phosphatidylserine is released upon injury and destruction of eukaryotic cells, these results suggest that phosphatidylserine may be an endogenous anti-inflammatory molecule. PMID- 1508950 TI - Prostaglandin synthetase, interleukin 1 and inflammation in the skin. PMID- 1508951 TI - Papaverine effects on PGI2 and TXA2 release from the canine vascular wall. AB - Operative manipulation of blood vessels might lead to spasm, thereby destroying the endothelial cell function: the spasm can be prevented by the vasodilator papaverine. To study if this was mediated via the prostanoid pathway the following investigation was undertaken: canine jugular veins and carotid arteries were dissected with or without papaverine. Vessel segments were then perfused with Hank's balanced salt solution for five times 15 min. Prostacyclin was measured as the stable degradation product 6-keto-PGF1 alpha and thromboxane as TXB2, by radioimmunoassay. Control arterial segments' 6-keto-PGF1 alpha release was initially 129.5 + 20.1 pg/mm2/15 min, and 29.7 + 10.4 after 60 min (p less than 0.05 vs initial value) and responded to arachidonic acid (AA) with an increase to 139.2 +/- 23.1 pg/mm2/15 min (p less than 0.05). Segments treated with papaverine had the same release as the controls. In venous segments there was a lower initial release (p less than 0.05) from segments given papaverine than from controls, but this was more likely an effect of papaverine on the assay. There was no difference in release of prostacyclin from segments given papaverine in the perfusate compared to controls when using 125I tracer. When using 3H tracer including absorption of free antigen to dextran coated charcoal, papaverine displaced the free tracer giving artificially low values. There was no effect of papaverine given intraoperatively on the TXB2 release, neither from arteries nor from veins. In another experiment the vessel wall tension was examined and the cyclooxygenase inhibitor diclofenac did not inhibit the vasodilating effect of papaverine.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1508952 TI - Relevance of vasoactive mediators for the blood pressure effects of intravenous arachidonic acid injection in rats. AB - Vasopressor response and release of eicosanoids following intravenous injection of arachidonic acid (AA) were examined in normotensive rats. AA administration caused a rapid initial fall of arterial pressure followed by a brief rise and a subsequent prolonged fall in anesthetized rats. Immediately after AA injection the blood levels of TXB2 and 6-keto-PGF1 alpha, the stable metabolites of TXA2 and prostacyclin, rose, from 1.52 +/- 0.23 ng/ml to 176.4 +/- 42.6 ng/ml and from 4.05 +/- 0.67 ng/ml to 171.4 +/- 31.2 ng/ml, respectively. Blood pressure behaviour and eicosanoid blood level were influenced by different inhibitors and antagonists of vasoactive mediators. The cyclooxygenase inhibitor acetylsalicylic acid completely eliminated the second blood pressure depression after AA injection and simultaneously diminished TXB2 and 6-keto-PGF1 alpha formation in murine blood, whereas the TXA2 receptor antagonist BM 13.177 prevented the return of the blood pressure to preinjection level after the initial brief fall in arterial pressure. Although the TXA2 synthase inhibitor HOE 944 markedly inhibited TXB2 formation, no influence on AA-induced blood pressure changes could be registered. The receptor antagonist of platelet activating factor BN 52021 and the serotonin and histamine receptor antagonist cyproheptadine also reduced TXB2 amounts, in murine blood without any effects on blood pressure behaviour. PMID- 1508953 TI - The correlation between rises in intracellular calcium and PGI2 production in cultured vascular endothelial cells. AB - Elevation of intracellular calcium in response to trypsin, bradykinin, thrombin or histamine is associated with a proportional increase in PGI2 production in cultured human umbilical vein endothelial cells (HUVEC), bovine pulmonary artery endothelial cells (CPAE), and bovine aortic endothelial cells (BAEC). The major agonists that induce increases in intracellular calcium and PGI2 production are thrombin and trypsin in HUVEC, bradykinin in CPAE, and bradykinin and trypsin in BAEC. These results suggest that endothelial cells derived from different species or sites require different agonists to induce increases in intracellular calcium and PGI2 production and that only agonists which increase intracellular calcium can stimulate PGI2 production. PMID- 1508954 TI - Production of platelet thromboxane A2 and arterial prostacyclin I2 from hypercholesterolemic rats. AB - The plasma cholesterol, plasma malonaldehyde (MDA), platelet thromboxane A2 (TXA2) and vascular prostacyclin (PGI2) were measured in male Sprague-Dawley rats fed diets supplemented with cholesterol (1%) and cholic acid (0.5%). For comparisons, measurements were made in rats fed normal diets. The concentration of cholesterol in the plasma of rats had reached a maximum in 1 week of feeding experimental diets. TXA2 production from collagen and thrombin stimulated platelets was significantly decreased in animals fed experimental diets for 1 week. The production of MDA in the plasma of animals fed experimental diets for 8 weeks was significantly lower compared to the animals fed normal diets. There was a small but significant reduction in the formation of PGI2 in rats fed experimental diets for 8 weeks. These data suggest that feeding cholesterol rich diets to rats alters the platelet membrane properties differently from human and rabbit. Furthermore, cholesterol feeding to rats had some damaging effect on the arterial PGI2 synthesis. PMID- 1508955 TI - Expression of the cDNA for NAD(+)-dependent 15-hydroxyprostaglandin dehydrogenase as a catalytically active enzyme in Escherichia coli. AB - NAD(+)-dependent 15-hydroxyprostaglandin dehydrogenase (15-PGDH) is a key enzyme involved in the catabolism of the prostaglandins. The cDNA for human placental 15 PGDH has been expressed in Escherichia coli as a catalytically active protein. The polymerase chain reaction was used to introduce restriction endonuclease sites at each end of the 15-PGDH coding sequence. The 15-PGDH DNA was then inserted into the bacterial expression plasmids pUC-18 and pUC-19 which contain the isopropyl-l-thio-beta-D-galactopyranoside (IPTG) inducible lacZ promoter. Extracts from E. coli containing these expression plasmids exhibited 15-PGDH activity which was inducible with (IPTG). Crude extracts from E. coli expressing 15-PGDH activity were found to contain proteins of the predicted sizes in stained SDS-polyacrylamide gels and in Western blots using human placental 15-PGDH antiserum. The specific activity in E. coli extracts was several hundred-fold higher than that seen in extracts from human placenta. PMID- 1508956 TI - Immunohistochemical localization of PGF2 alpha receptor in the rat ovary. AB - As a step towards understanding the role of prostaglandin F2 alpha (PGF2 alpha) in ovarian function, a rabbit antiserum against purified PGF2 alpha receptor (PGF2 alpha-R) was produced. This report details the use of this antiserum in immunohistochemical staining of ovaries of non-pregnant and pregnant rats to ascertain which cell types, in vivo, possess PGF2 alpha-R. In non-pregnant rats, three ovarian cell subpopulations contain immunoreactive PGF2 alpha-R. These include: a subpopulation of the cells found in corpora lutea, a subpopulation of the thecal cells surrounding secondary and mature (Graafian) follicles, and a subpopulation of primary and secondary interstitial cells. The ovarian tissues and cell types in which immunoreactive PGF2 alpha-R cannot be demonstrated include: the serosa overlying the ovary and its vessels, the coelomic epithelium and its underlying cortical stroma, medullary stroma and vessels, granulosa cells of primary, secondary and mature follicles, the oocyte, and the blood vessels and stroma within corpora lutea. PGF2 alpha-R immunohistochemical staining of corpora lutea from non-pregnant animals was examined both prior to the start of luteolysis and during luteolysis. During luteolysis, cells undergoing apoptosis stained for the presence of PGF2 alpha-R. PGF2 alpha-R immunohistochemical staining was also examined in corpora lutea during pregnancy and until 4 days postpartum. The major findings here were the apparent large increase in staining intensity of granulosa-lutein cells during pregnancy, and the loss of PGF2 alpha R immunopositivity of the granulosa-lutein cells during the postpartum period. In summary, three ovarian cell subpopulations, all of which can secrete steroids, possess immunoreactive PGF2 alpha-R. PMID- 1508957 TI - Prostaglandin D2 in cultured capillary and microvascular endothelium of human brain. AB - Production of prostaglandin D2 (PGD2) was investigated in cultured endothelial cells derived from capillaries and microvessels (small and large) of human brain using radioimmunoassays. Peptides, catecholamines, thrombin, protein kinase C activating phorbol ester and calcium ionophore greatly stimulated the secretion of endothelial PGD2. Secretion of PGD2 induced by vasoconstricting peptides, angiotensin II and arginine-vasopressin, was almost completely abolished by their respective specific receptor antagonists [Sar1, Ala8]-Ang II and [1-6(beta mercapto-beta,beta-cyclopentamethylene propionic acid) 2-O-methyltyrosine]. Thus, the augmented production of PGD2 by angiotensin II and arginine-vasopressin is a receptor-mediated event. It also indicates that the EC have specific angiotensin II and arginine-vasopressin (V1) receptors. This study represents the first demonstration of vasoactive agents modulating PGD2 production in capillary and microvascular endothelium of human brain. PMID- 1508958 TI - Fatty acid changes during the induction of differentiation of human promyelocytic leukemia (HL-60) cells by phorbolmyristate acetate. AB - We studied fatty acid changes that are likely to occur during phorbolmyristate acetate (PMA)-induced differentiation of HL-60 cells. It was observed that PMA induced differentiation is associated with increased uptake, but not synthesis, of fatty acids. Fatty acid analysis revealed that arachidonic acid (AA), 20:5 n-3 and 22:6 n-3 levels are reduced with a concomitant increase in 22:5 n-6 in the phospholipid fraction. In the FFA fraction there are increases in free AA, free 20:5 n-3, 22:5 n-3 and 22:6 n-3, and a fall in free 22:5 n-6 in PMA-treated cells. PMA-induced differentiation and nitroblue tetrazolium reduction by PMA treated cells was only partially inhibited (about 20-30%) by indomethacin and nordihydroguiaretic acid (cyclooxygenase and lipoxygenase inhibitors respectively), but not by superoxide dismutase, catalase or mannitol. These results indicate that PMA-induced differentiation of HL-60 cells is accompanied by specific changes in the fatty acid composition of the cells. PMID- 1508959 TI - Endogenous inhibitors of human placental prostaglandin dehydrogenase. AB - The presence of endogenous inhibitors of NAD(+)-dependent 15-hydroxyprostaglandin dehydrogenase (PGDH) has been indicated by increasing total activity after the initial purification step of PGDH in human placenta. Based on this observation, we tried to characterize and analyze endogenous inhibitors of PGDH in human placenta in this study. The inhibitors were extracted from the supernatant by precipitation at pH 5.2 and partially purified by acetone precipitation and by thin layer chromatography. The inhibitors were stable to heating at 100 degrees C for 10 min, and to trypsin digestion. The pattern of inhibition was competitive with regard to PGE2 and uncompetitive with regard to NAD at pH 8.0. The Ki value for PGE2 was 18.9 microM. Analysis by gas chromatography and mass spectrometry indicated that the inhibitors consisted of fatty acids which were palmitic, stearic, oleic and linoleic acids. Myristic, palmitic and stearic acids were confirmed to exert an inhibitory action on PGDH and showed a competitive inhibition pattern. Stearic acid was less potent in inhibition than other fatty acids. These findings suggest that intracellular fatty acids may play a unique role in the control of PGDH activity. PMID- 1508960 TI - Effects of different cyclooxygenase inhibitors on the segmental distribution of pulmonary vascular resistance in the dog. AB - An increase in pulmonary vascular resistance (PVR) after cyclooxygenase inhibition (COI) is well documented in the dog, but the site of vasoconstriction to chemically distinct cyclooxygenase inhibitors is largely unknown. The purpose of the present study was to examine and compare equimolar concentrations of three chemically unrelated cyclooxygenase inhibitors, indomethacin (INDO; n = 6), meclofenamate (MECLO; n = 6) and ibuprofen (IBU; n = 5), upon the longitudinal distribution of PVR in the isolated canine lower left lung lobe perfused at constant flow with autologous blood. At successive increases in the blood concentration of each cyclooxygenase inhibitor, PVR was partitioned into upstream (arterial, Ra), middle (Rm) and downstream (venous, Rv) resistance by arterial and venous flow occlusion with capillary pressure estimated by a double flow occlusion technique. All three cyclooxygenase inhibitors produced significant pulmonary vasoconstriction with the largest increase in PVR after INDO (104 +/- 21%) and the smallest after IBU (69 +/- 10%). The PVR increase in the INDO and MECLO group was related to an elevation in both Ra (p less than 0.01) and Rv (p less than 0.01), whereas only Rv was increased by IBU (p less than 0.01). While none of the cyclooxygenase inhibitors increased Rm (p greater than 0.05), capillary pressure was increased from pretreatment levels by each cyclooxygenase inhibitor. Although each of the three chemically distinct cyclooxygenase inhibitors raised PVR, the segmental distribution of PVR and the magnitude of the capillary pressure increase varied at equimolar blood concentration. PMID- 1508961 TI - Effects of methimazole on low-renal-mass hypertension: changes in blood pressure and pressor responsiveness to vasoconstrictors. AB - The administration of the antithyroid drug methimazole to rats via drinking water prevented the development of hypertension that usually accompanies subtotal nephrectomy and saline drinking (1% NaCl). In methimazole-treated rats, elevated blood pressure induced 5 weeks previously returned to normotensive levels. Pressor responsiveness to angiotensin, vasopressin and norepinephrine in unanesthetized rats was studied after prevention of hypertension in control, low renal-mass hypertensive (LRM) and low-renal-mass methimazole-treated (LRM-M) rats, and in the reversion study in LRM and LRM-M rats. In LRM rats, responsiveness to vasoconstrictors was increased, whereas responsiveness to vasoconstriction was clearly reduced in LRM-M rats after prevention and reversion studies. These results suggest that (a) thyroid hormones are required in the early and established phases of LRM hypertension, and (b) the decreased pressor responsiveness to vasoconstrictors may play a role in the prevention and reversion of this type of hypertension following methimazole administration. However, the changes in pressor responsiveness may also be secondary to the reduction in blood pressure. PMID- 1508962 TI - Muscarinic binding sites on bovine pulmonary arterial endothelial cells in culture. AB - We have investigated the presence and nature of muscarinic binding sites on membranes from cultured bovine pulmonary arterial endothelial cells (BPAE). BPAE were harvested and subcultured nonenzymatically; experiments were performed 3-5 days postconfluence and between 10 and 25 passage numbers. Utilizing radioligand binding techniques with the muscarinic receptor antagonists [3H]3-quinuclidinyl benzilate ([3H]QNB) and [3H]N-methylscopolamine ([3H]MS) as probes, we identified a small population of atropine-sensitive muscarinic sites (1,800-2,000 sites/cell or 7-8 fmol/mg protein). Muscarinic binding sites on BPAE membranes resembled classical muscarinic receptors in that (a) the binding of 2 nM [3H]QNB was inhibited by muscarinic agonists and antagonists, (b) [3H]QNB binding was 30 times more sensitive to R(-)- than to S(+)-QNB, (c) binding of the muscarinic receptor agonist carbamylcholine involved high and low affinity components, (d) the stable GTP analog, Gpp(NH)p (100 microM) shifted agonist binding curves to the right by a factor of three, and (e) the high affinity binding of the agonist [3H]oxotremorine-M to muscarinic receptors was depressed by Gpp(NH)p. On the other hand, gallamine, which allosterically regulates muscarinic receptor binding in other tissues, did not affect the rates of dissociation of [3H]QNB, [3H]MS or [3H]oxotremorine-M from BPAE binding sites. We concluded that BPAE in culture exhibit muscarinic binding sites which possess many but not all of the properties associated with classical muscarinic receptors. PMID- 1508964 TI - Probucol attenuates a reduction in serum immunoreactive insulin levels by interleukin in adrenalectomized rats. AB - We determined a protective action of probucol (4,4'-[isopropylidenedithio]bis[2,6 di-tert-butylphenol]) on the reduction of serum immunoreactive insulin (IRI) levels by recombinant human interleukin-1 beta (IL-1) in adrenalectomized rats. IL-1 reduced the serum IRI levels 4 h after injection in rats fed a standard diet. However, IL-1 failed to inhibit serum IRI levels in rats fed a diet containing 1% probucol. In contrast, IL-1 decreased plasma glucose levels in both groups. Although IL-1 reduced plasma prostaglandin (PG) E2 levels in standard diet-fed rats, IL-1 did not affect plasma PGE2 levels in the animals fed the probucol-containing diet. The present study suggested that the free radical scavenger action of probucol can block the IL-1 effect on serum IRI levels. PMID- 1508963 TI - Effect of phorone and allopurinol on ischemia-reperfusion injury in gastrointestinal mucosa of the rat. AB - We studied the effect of inhibition of oxyradical formation and of endogenous glutathione (GSH) depletion on lesion formation in the gastrointestinal tract in a modified rat hemorrhagic shock model (1 h hypotension and 1 h reperfusion). Allopurinol, an inhibitor of xanthine oxidase, did not protect against lesion formation. This suggests that oxygen radicals generated from xanthine oxidase may not be the major cause of injury under these conditions of prolonged 'ischemia' reperfusion. Phorone (diisopropylideneacetone), a GSH depletor, decreased mucosal GSH levels in the corpus, duodenum and small intestine, and also significantly reduced lesion formation histologically in the corpus, antrum, duodenum and small intestine. However, there was no significant differences in mucosal blood flow (as estimated by changes in mucosal hemoglobin concentrations and oxygen saturation of mucosal hemoglobin) in the corpus, antrum, duodenum and small intestine between phorone-pretreated and control rats. We conclude that phorone decreased mucosal GSH concentrations and exerted a protective effect against hemorrhagic shock-induced gastrointestinal mucosal lesions. The protective effect appears to be independent of mucosal blood flow. PMID- 1508965 TI - Dose-dependent actions of spironolactone on the inner and outer zones of the guinea pig adrenal cortex. AB - The results of prior in vitro studies indicated that spironolactone (SL) caused far greater degradation of cytochromes P-450 in the outer (zona glomerulosa plus zona fasciculata) than inner (zona reticularis) zone of the guinea pig adrenal cortex and selectively decreased microsomal 17 alpha-hydroxylase activity. Studies were done to determine if the effects of SL in vivo were similarly zone and/or enzyme selective. Administration of high doses of SL (100 mg/kg) to guinea pigs altered the gross appearance of the adrenal glands and caused declines in 17 alpha- and 21-hydroxylase activities in both inner and outer zone microsomal preparations. The losses in enzyme activities were accompanied by decreases in microsomal cytochrome P-450, cytochrome b5 and heme concentrations, and in mitochondrial P-450 levels in both zones. Microsomal P-450(17 alpha) apoprotein levels were also decreased in both zones. A lower dose (25 mg/kg) of SL did not affect adrenal morphology, but decreased microsomal P-450 levels in both zones. Neither mitochondrial P-450 nor microsomal b5 concentrations were affected in either zone. 17 alpha-Hydroxylase activities and P-450(17 alpha) apoprotein concentrations in both zones were decreased by the lower dose of SL, but 21 hydroxylase activity declined in the inner zone only. The results indicate that very high doses of SL have a variety of nonspecific effects on the adrenals which may be the consequence of drug toxicity. Nontoxic doses exert more selective effects on microsomal cytochromes P-450 in both adrenal zones, more closely mimicking the in vitro actions of the drug. PMID- 1508966 TI - Defect of the potassium transport process in the kidney of spontaneously hypertensive rats. AB - We investigated the natriuretic and kaliuretic effect of distal tubular diuretics in saline-loaded spontaneously hypertensive Wistar rats (SHR) from three different sources and normotensive Wistar rats (NWR). Orally administered early distal tubular diuretics (hydrochlorothiazide, chlorthalidone, metolazone, indapamide and cicletanine) caused much less potassium excretion in SHR than in NWR, whereas the magnitude of concurrent natriuresis was similar in both NWR and SHR. The intriguing renal handling of potassium excretion was exemplified by hydrochlorothiazide, for which enhanced kaliuresis was dose dependent in NWR but not in SHR. The doses tested ranged from 1 to 100 mg/kg, p.o. Amiloride, a late distal tubular diuretic, was also evaluated for its effect on sodium and potassium excretion in NWR and SHR. Amiloride produced potassium retention more effectively in NWR than in SHR, although the magnitude of natriuresis was similar. The difference between SHR and NWR with regard to potassium-retaining activity of amiloride was consistent at all doses tested (1-30 mg/kg, p.o.). In conclusion, it was suggested that SHR appear to have a genetic defect in potassium transport in the distal nephron. PMID- 1508967 TI - A beta-carboline derivative (ZK 93426) counteracts the cardiorespiratory depressant effects of intravenous midazolam. AB - The purpose of this study was to test the effects of the new beta-carboline ZK 93426 on midazolam-induced cardiorespiratory depression. Seven pentobarbital anesthetized (35 mg/kg i.p.) cats were treated with intravenous midazolam (2 mg/kg) while monitoring the respiratory minute volume (VE), tidal volume, respiratory rate, blood pressure, heart rate and expired CO2. Midazolam caused significant decreases in VE (p less than 0.05) and blood pressure (p less than 0.05). ZK 93426 (5 mg/kg i.v.) antagonized these effects and produced significant increases in VE and blood pressure that resulted in the return of these variables to premidazolam control values. In 4 animals with morphine-induced respiratory depression, intravenous ZK 93426 failed to antagonize the respiratory effects of morphine. Administration of intravenous ZK 93426 alone to 4 pentobarbital anesthetized animals also failed to produce significant changes in cardiorespiratory activity. We conclude that ZK 93426 is effective in counteracting the cardiorespiratory depressant effects of midazolam and that these effects appear to be specific. The present data suggest that this compound may be useful for the treatment of benzodiazepine oversedation and overdose. PMID- 1508968 TI - Effects of haloperidol, bromocriptine and amphetamine on the development of Ehrlich ascites carcinoma in mice. AB - We determined the effect of 13 days of treatment with 2.0 mg/kg haloperidol, 4.0 mg/kg bromocriptine or 2.0 mg/kg amphetamine on the number of tumor cells of mice bearing Ehrlich ascites carcinoma. The dopaminergic blocker significantly reduced the number of tumor cells of experimental mice, but the two dopamine-mimetic drugs used did not significantly affect tumor development. These results suggest that although neuroleptic drugs to inhibit Ehrlich ascites tumors, this effect does not seem to be related to changes in dopaminergic neuronal transmission. PMID- 1508969 TI - Effects of potassium channel blockers on the negative inotropic responses induced by cromakalim and pinacidil in guinea pig atrium. AB - The K+ channel openers cromakalim and pinacidil induced a concentration-dependent reduction in atrial contraction force with EC50 values of 25 +/- 2 and 37 +/- 2 mumol/l, respectively. This depressant effect was antagonised by 50 mumol/l tacrine which displaced the concentration-response curves of cromakalim and pinacidil to the right. The respective DR50 values were 3.8 and 2.3. Increasing the tacrine concentration (100 and 500 mumol/l) produced no additional effect on the concentration-response relationships. Addition of 1 mumol/l atropine enhanced the antagonism due to tacrine by increasing the DR50 value from 3.8 to 6.5 for cromakalim and from 2.3 to 5.2 for pinacidil. Glibenclamide, an ATP-sensitive K+ channel blocker, competitively inhibited the negative inotropic effects of cromakalim and pinacidil. The respective dissociation constants for glibenclamide against cromakalim and pinacidil were 0.57 and 0.35 mumol/l. Neither apamin nor variation in external Ca2+ concentration affected the negative inotropic effects of the K+ channel openers. It was suggested that the mechanical effects of cromakalim and pinacidil are mediated through the ATP-sensitive K+ channels in the heart. PMID- 1508970 TI - Agonist and antagonist activity during voluntary upper-limb movement in patients with stroke. AB - Forty-four patients with hemiplegia following stroke and 10 nondisabled subjects were studied to examine the contributions inadequate motor unit recruitment and co-contraction attributable to impaired antagonist inhibition play in the movement disorder of the hemiplegic arm. Electromyographic data were recorded from agonist and antagonist muscles while subjects attempted six specified tasks. Data from subjects who could complete the tasks were compared with those who could not complete the tasks. Differences between the two groups were found in the electromyographic data obtained from the agonist muscles. Electromyographic values were consistently and significantly lower in patients who were unable to complete the tasks than in patients who were able to complete the tasks. In the antagonist muscles, a significant difference was noted only once; in this case, the EMG values were again lower in the group of patients who were unable to complete the task. Inadequate recruitment of agonists, not increased activity in the antagonists, was a consistent finding in patients who were unable to carry out the movement tasks. This study theoretically supports aiming treatment efforts at improving motoneuron recruitment rather than reducing activity in antagonists while retraining arm function. PMID- 1508971 TI - Assistive positioning as a control parameter of social-communicative interactions between students with profound multiple disabilities and classroom staff. AB - This study examined the effects of assistive positioning on social-communicative interactions between 10 students, 6 to 12 years of age, with profound multiple disabilities, and their classroom staff. Interactions were videotaped in the students' classrooms when each student was positioned using a wheelchair, a sidelyer, and a mat on the floor. Data were analyzed by repeated-measures analysis of variance. During unstructured interactions, adults initiated communication at higher rates when students were positioned in their wheelchairs. During structured interactions, when students were given standardized opportunities for interaction, students functioning at lower levels of communication development were more communicative when they were supine on a mat than when in their wheelchairs or a sidelyer. In dynamic systems terms, position served as a control parameter of both adult and student communicative behaviors, which should be considered when recommending use of assistive positioning equipment for students with severe disabilities. PMID- 1508972 TI - Comparison of three noninvasive methods for measuring scoliosis. AB - The premise behind most noninvasive techniques for the measurement of scoliotic conditions of the spine is that the lateral distortion of the spine relates directly to transverse rib cage deformity within the transverse plane. The focus of this study was to examine this assumption by comparing different noninvasive methods for the assessment of scoliotic curves. The three techniques examined were (1) use of the Scoliometer (SCOL), (2) use of the back-contour device (BCD), and (3) use of moire topographic imaging (MTI). Fourteen subjects (10 female, 4 male) with idiopathic adolescent scoliosis were measured. Posterior-anterior radiographs were obtained for the clinical assessment of all subjects and were subsequently used to determine Cobb angles. Significant correlations between axial trunk rotation and Cobb-angle measurements were observed in the thoracic region (MTI, r = .80, df = 10, P less than .005; BCD, r = .70, df = 10, P less than .025; SCOL, r = .59, df = 10, P less than .025) but were not found within the lumbar region (MTI, r = .42; BCD, r = .17; SCOL, r = .20). Factors other than trunk deformity, such as the posture assumed by the subject during measurement, may have influenced axial trunk rotation. Hence, the techniques appear to provide valid estimations of lateral curvature of the spine in the thoracic region of the trunk but not the lumbar region. The results suggest that the measurement techniques cannot be used interchangeably in clinical recording. PMID- 1508973 TI - Alterations in electrical pain thresholds by use of acupuncture-like transcutaneous electrical nerve stimulation in pain-free subjects. AB - Acupuncture-like transcutaneous electrical nerve stimulation (ALTENS) was compared with a placebo treatment in altering acute electrical pain thresholds. Ten pain-free subjects underwent, on different days, an acclimatization session, an ALTENS treatment, and a placebo treatment in a cross-over design. Electrical sensation and pain thresholds were measured from the tip of the index finger bilaterally at 15-minute intervals twice before, once during, and three times after a 30-minute treatment session. The ALTENS treatment was given at 4 Hz at an intensity just below pain threshold delivered to acupuncture points in the hand and wrist. The placebo treatment was similarly delivered, except that the intensity of stimulation was just above sensation threshold. Neither the ALTENS treatment nor the placebo treatment produced a significant change in pain threshold. There was no correlation between initial pain threshold and change in pain threshold. Implications for the modulation of pain are discussed. PMID- 1508974 TI - Influence of high voltage pulsed current on edema formation following impact injury in rats. AB - High voltage pulsed current (HVPC) has been shown to be effective in curbing posttraumatic edema formation in frogs. The purpose of this study was to establish the utility of HVPC in controlling edema formation in a mammalian model. Both feet of 20 anesthetized rats were traumatized following initial determination of hind-limb volumes. Four 30-minute cathodal HVPC treatments at 120 pulses per second and 90% of visible motor threshold interspersed with 30 minute rest periods were applied to one randomly selected hind limb of each rat via the immersion technique. The other hind limb served as a control. Limb volumes were measured after each treatment and rest period. All data were expressed as changes from pretrauma limb volumes in milliliters per kilogram of body weight; these data were analyzed by repeated-measures analyses of variance and post hoc paired t tests. Volumes of untreated limbs were significantly greater than volumes of treated limbs after the second treatment. Evidence of significant treatment effects in frogs, and now rats, provides a compelling rationale for initiating trials of efficacy of cathodal HVPC in inhibiting acute edema formation in humans. PMID- 1508975 TI - Living without student research projects. PMID- 1508976 TI - Photoperoxidation of cholesterol in homogeneous solution, isolated membranes, and cells: comparison of the 5 alpha- and 6 beta-hydroperoxides as indicators of singlet oxygen intermediacy. AB - Singlet oxygen (1O2) can react with cholesterol (Ch) to give three possible ene addition hydroperoxides: 3 beta-hydroxy-5 alpha-cholest-6-ene-5-hydroperoxide (5 alpha-OOH), 3 beta-hydroxycholest-4-ene-6 alpha-hydroperoxide (6 alpha-OOH), and 3 beta-hydroxycholest-4-ene-6 beta-hydroperoxide (6 beta-OOH). The rates of dye sensitized photogeneration and also the fates of 5 alpha-OOH and 6 beta-OOH in membrane bilayers have been studied and compared. Irradiation of unilamellar [14C]Ch/phospholipid vesicles in the presence of aluminum phthalocyanine tetrasulfonate or merocyanine 540 resulted in formation of 5 alpha-OOH and 6 beta OOH, as determined by high performance liquid chromatography with radiochemical or electrochemical detection. The initial rate of 6 beta-OOH formation was 30-35% that of 5 alpha-OOH in a variety of liposomal systems. However, after a lag, 5 alpha-OOH invariably decayed via allylic rearrangement to 7 alpha-OOH (also known to be a free radical product), whereas 6 beta-OOH accumulated in unabated fashion until Ch depletion became limiting. Photooxidation of Ch in an isolated natural membrane (erythrocyte ghost) or in L1210 leukemia cells gave similar results. When the reaction was carried out in pyridine or methanol, the rate of 6 beta-OOH formation relative to 5 alpha-OOH was reduced by approximately half, with essentially no isomerization of the latter to 7 alpha-OOH.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1508977 TI - 9,11-Dicis-12-fluororhodopsin. Chromophore properties from 19F-NMR studies. AB - From a 19F-NMR study of 9,11-dicis-12-fluororhodopsin and its photobleached product, we concluded that the initially formed chromophore retained its configuration and the photoproduct corresponded to the two-bond isomerized all trans. Upon standing, it slowly isomerized to the 9-cis isomer. The method represents a direct, non-destructive procedure for determining configuration purity of the pigment formed. Its unique fluorine opsin shift value is consistent with the expected different orientation of the fluoro-substituent in a dicis pigment. PMID- 1508978 TI - Evidence for an ultraviolet sunscreen role of the extracellular pigment scytonemin in the terrestrial cyanobacterium Chlorogloeopsis sp. AB - The proposed photoprotective role of the UV-A absorbing, extracellular pigment scytonemin was studied in the terrestrial cyanobacterium Chlorogloeopsis sp. strain O-89-Cgs(1). UV-A (315-400 nm) caused growth delay, cell growth restarting only when scytonemin had accumulated in the extracellular envelopes. Cultures with scytonemin were more resistant to photoinhibition of photosynthesis than cultures without scytonemin, the differential resistance being much greater to UV A-caused photoinhibition than to photoinhibition caused by visible light. The presence of scytonemin in the extracellular envelopes was correlated with the inability of UV-A radiation to induce strong photopigment fluorescence (685 nm emission), regardless of the specific content os photosynthetic pigments. The physical removal of the scytonemin containing extracellular envelopes brought about the loss of UV-A resistance as measured by photobleaching rates of chlorophyll a under conditions of physiological inactivity (desiccation). These observations provide strong evidence for the proposed protective role of scytonemin, as a passive UV-A sunscreen, in cyanobacteria. PMID- 1508979 TI - Inhibition of 12-O-tetradecanoylphorbol-13-acetate-induced tumor promotion in murine skin by systemic effects of ultraviolet irradiation. AB - Systemic effects of UVB irradiation (280-320 nm) have been shown to prevent subsequent chemical tumorigenesis induced by an initiation-promotion protocol. The present investigation was designed to determine whether initiation or promotion is prevented by UV irradiation. Groups of 25 B6D2F1/J mice received 12 weeks of intermittent dorsal UVB radiation treatments administered before, or 3 weeks after, initiation with a single application of 7,12 dimethylbenz[a]anthracene on the ventral skin. All mice were promoted ventrally with 5 micrograms 12-O-tetradecanoylphorbol-13-acetate (TPA) applied three times weekly throughout the experiment. UV irradiation consisted of five 30-min exposures per week to a bank of 6 Westinghouse FS40 sunlamps. UV irradiation applied before or after initiation resulted in a decrease of 18-16 tumors per group of 25 mice, for a reduction of 61 and 50%, respectively, at 24 weeks after the first TPA treatment. Thus, prevention of tumor development was similar whether the UV influence was present or not during initiation. This finding suggests that the UV prevention of promotion could account for UV inhibition of skin tumors induced by an initiation-promotion regimen. Consistent with this concept, pretreatment of mice with dorsal UVB radiation was found to reduce DNA synthesis after exposure to TPA by 46%, although it did not decrease tritiated benzo[a]pyrene binding to DNA, in ventral epidermis. Thus, UVB irradiation systemically reduced TPA-induced tumor promotion in murine skin. PMID- 1508980 TI - Effect of vitamin E on cytotoxicity, DNA single strand breaks, chromosomal aberrations, and mutation in Chinese hamster V-79 cells exposed to ultraviolet-B light. AB - The effect of pretreatment with vitamin E on cytotoxicity, DNA single strand breaks, and chromosomal aberrations as well as on mutation induced by ultraviolet B light (UV-B) was investigated in Chinese hamster V-79 cells. Cellular pretreatment with non-toxic levels of 25 microM alpha-tocopherol succinate (vitamin E) for 24 h prior to exposure resulted in a 10-fold increase in cellular levels of alpha-tocopherol. Using a colony-forming assay, this pretreatment decreased the cytotoxicity of UV-B light. However, alkaline elution assays demonstrated that pretreatment with vitamin E did not affect the number of DNA single strand breaks caused by UV-B light. In addition, UV-B exposure produced a dose-dependent induction of chromosomal aberrations and mutations at the HGPRT locus, and neither of these actions of UV-B was influenced by pretreatment with the vitamin. These results suggest that vitamin E protects cells from UV-B induced cytotoxicity, possibly through its ability to scavenge free radicals. The results also suggest that the extent of genotoxicity induced by UV-B light may not correlate directly with the cytotoxic action of this wavelength region in sunlight. PMID- 1508981 TI - Photodynamic therapy of chemically- and ultraviolet B radiation-induced murine skin papillomas by chloroaluminum phthalocyanine tetrasulfonate. AB - Photodynamic therapy (PDT) of cancer combines irradiation of tumors with visible light following selective uptake of the photosensitizer by the tumor cells. PhotofrinR-II (Pf-II) is the only photosensitizer which is in clinical use in PDT, whereas chloroaluminum phthalocyanine tetrasulfonate (AlPcTS) has also shown promise in preclinical studies. In most such studies, the effectiveness of the photosensitizers has been assessed in implanted tumor model systems rather than in model systems where tumors are allowed to grow in their own connective tissue matrix. In this study the pharmacokinetics, tumor ablation capability and cutaneous photosensitization response of AlPcTS have been assessed in mice bearing chemically- and ultraviolet B radiation (UVB)-induced benign skin papillomas. When tumor-bearing animals were injected intraperitoneally with AlPcTS (5 mg/kg body wt), maximum tumor:normal skin ratio of 2.4 was observed at 48 h, at which time the mice were irradiated within the absorption spectrum of the photosensitizer. In tumor ablation studies with SENCAR mice bearing chemically-induced skin tumors, AlPcTS resulted in greater than 80% ablation in tumor volume at 20 days post-irradiation. In cutaneous photosensitization response, AlPcTS produced only transient effects (no effect after 24 h) in SENCAR mice. Pharmacokinetics data, tumor ablation effects and cutaneous photosensitization response of AlPcTS were comparable in SKH-1 hairless mice bearing UVB-induced skin tumors. Our data indicate that AlPcTS produces significant photodynamic effects towards the ablation of murine skin tumors, and that it does not produce prolonged cutaneous photosensitivity. PMID- 1508982 TI - Lipoprotein-mediated distribution of N-aspartyl chlorin-E6 in the mouse. AB - The localization of many photosensitizing agents has been attributed to distribution of low density lipoprotein (LDL)-bound drug as a function of the relative numbers of LDL receptors in different tissues. While the chlorin derivative NPe6 is a potent photosensitizing agent in the mouse, it binds mainly to mouse plasma high density lipoproteins (HDL) and albumin, with only 1% bound to LDL. This pattern suggests only a minor role for the LDL-receptor pathway with regard to N-aspartyl chlorin e6 (NPe6) biodistribution. Moreover, patterns of accumulation of radioactive NPe6, LDL and HDL in murine tissues are consistent with the suggestion that distribution of NPe6 to different tissues cannot be explained on the basis of an LDL-mediated mechanism. PMID- 1508983 TI - Conformational changes of cytosolic loops of bovine rhodopsin during the transition to metarhodopsin-II: an investigation by Fourier transform infrared difference spectroscopy. AB - In order to assign the structural changes of the protein, observed in the Fourier transform infrared (FT-IR) difference spectra of the rhodopsin-metarhodopsin-II transition, to specific regions of the protein, rhodopsin was treated by proteases. Nonilluminated and bleached rhodopsin was treated with protease K and papain. Rhodopsin digested in the bleached state was subsequently regenerated with 11-cis-retinal. From these modified samples the rhodopsin-metarhodopsin-II FT-IR difference spectra were measured. Comparing the difference spectra with that of unmodified rhodopsin, clear deviations in the amide-I and amide-II spectral range are observed. This indicates that in the unmodified pigment conformational changes of those parts of the cytosolic surface take place which are susceptible to the proteases. From the larger spectral changes obtained with samples digested in the bleached state it is concluded that the extent of modification is larger. The difference spectra of rhodopsin modified with 10 mM dithiothreitol support the existence of the 4th loop which also undergoes conformational changes. The spectral changes are interpreted in terms of a transition of an ordered structure of the loops in rhodopsin to a more random structure in metarhodopsin-II. The results demonstrate that by combining FT-IR spectroscopy with protein modification by specific proteases, conformational changes of the protein can be localized to specific regions. PMID- 1508984 TI - Iron-sulfur centers as endogenous blue light sensitizers in cells: a study with an artificial non-heme iron protein. AB - The possible involvement of Fe-S clusters in photodynamic reactions as endogenous sensitizing chromophores in cells has been investigated, by using an artificial non-heme iron protein (ANHIP) derived from bovine serum albumin and ferredoxins isolated from spinach and a red marine algae. Ferredoxins and ANHIP, when exposed to visible light, generate singlet oxygen, as measured by the imidazole plus RNO method. Irradiation with intense blue light of the ANHIP-entrapped liposomes caused severe membrane-damage such as liposomal lysis and lipid peroxidation. In the presence of ANHIP, isocitrate dehydrogenase and fructose-1,6-diphosphatase were photoinactivated by blue light. However, all of these photosensitized reactions were significantly suppressed by a singlet oxygen (1O2) quencher, azide, but enhanced by a medium containing deuterium oxide. Further, the Fe-S proteins with the prosthetic groups destroyed did not initiate the blue light induced reactions. In addition, the action spectrum for 1O2 generation from ANHIP was very similar to the visible absorption spectrum of Fe-S centers. The results obtained in this investigation appear consistent with the suggestion that Fe-S centers are involved in photosensitization in cells via a singlet oxygen mechanism. PMID- 1508985 TI - Photochemistry of halogen pyrimidines: iodine release studies. AB - The feasibility of using direct iodide (I-) measurements to monitor the photochemistry of the halogenated pyrimidines 5-iodocytosine and 5-iodouracil and their corresponding deoxynucleosides was examined. Radiation from either a germicidal lamp (lambda = 254 nm) or a sunlamp (lambda greater than 290 nm) was employed to induce homolytic splitting of the carbon-iodine bond and the release of iodine atoms. These atoms combine to form I2 which reacts with water to ultimately form I- and iodate (IO3-). The formation of I- was followed using either high performance liquid chromatography with electrochemical detection or a specific ion electrode. IO3- was assayed spectroscopically following its conversion to triiodide. The yields of I- relative to starting material destroyed were either close to the theoretical limit of 83% or higher depending upon (a) the compound being irradiated, (b) the irradiation wavelength and (c) the extent of exposure. Yields of iodide greater than 83% are generally accounted for by a concomitant reduction in the yield of iodate such that the sum I(-) + IO3- is approx. 100%. Because iodate is photochemically reduced to iodide by 254 nm but not sunlamp irradiation, exhaustive irradiation at 254 nm converts all of the iodate present to iodide. These studies have application to the use of photochemical methods for quantitating the percent substitution of iodinated pyrimidines in DNA, and should be useful in following the photochemistry of IdUrd and IdCyd substituted DNA. PMID- 1508986 TI - Room-temperature steady-state fluorescence properties of poly(dG-dC).poly(dG-dC). AB - We report the steady-state fluorescence properties of the alternating polynucleotide poly(dG-dC).poly(dG-dC) in low-salt solution at room temperature for excitation at the Hg lines 265, 280 and 297 nm. Its fluorescence spectrum peaks at about 325 nm and, within the experimental error, its shape does not change significantly with the excitation wavelength. The fluorescence anisotropy is found to decrease strongly for short-wavelength excitation, a behavior which is very similar to that exhibited by free guanine. In view of the fact that the anisotropy for free cytosine is virtually constant at the aforementioned three excitation wavelengths, the results suggest that in this polynucleotide the emission stems from guanine. The values of the fluorescence quantum yield for the three excitation wavelengths are found to be very low, 0.8 x 10(-5), 0.8 x 10( 5), and 2.8 x 10(-5), respectively; these are compatible with transfer of energy from the lower-energy electronic state of guanine, before vibronic relaxation is established, to cytosine. Upon denaturation, the fluorescence spectrum becomes very broad and the fluorescence quantum yield increases; these observations support the authenticity of the emission from the nondenatured polynucleotide. PMID- 1508987 TI - Small acidic peptides from wheat germ chromatin. II. Regulatory activity in specific transcription systems reconstituted in vitro. AB - A variety of evidence suggests that a family of chromatin peptides (CPs), characterized by 1000D molecular weight, a pH dependent association to DNA and a prevailing presence of acidic amino acids in their structure, is involved in the regulation of genes expression. Nevertheless their action mechanism is still unknown. In our in vitro specific RNA transcription systems the CPs affect the initiation and not the elongation. Furthermore they inhibit the RNA transcription by interaction with the DNA rather than with the enzyme. The phagic in vitro specific RNA transcription is less affected by CPs than the eubacteric system, suggesting a kind of selectivity for target DNA sequences involved in the initiation of transcription. PMID- 1508988 TI - Biodynamics of living cells: the molecule-contraction theory. AB - Living cells can carry out work, by transforming chemical to mechanical energy. It has been found that such biodynamic activities are carried out by filaments built of proteinaceous subunits. Since work in general involves contractions, the proteins which are involved in the execution of work may thus be called "contractile proteins". There seem to be three such proteins: flagellin, actin and tubulin, forming bacterial flagella, actin filaments and microtubules, respectively. Myosin is also a filament-forming protein, important for the activity of actin filaments, notably in striated muscle cells, but it is not a contractile protein. When a muscle works, that is, contracts, then it is observed that the actin filaments slide in between the myosin filaments, and this observation has been used to develop a theory of contraction, the "sliding filament" theory. But it should be emphasized that this theory is essentially descriptive, not explanatory, and the main point in muscular activity, the presence of two kinds of filament, is not found in most other cases when cells are performing physical work. In order to solve this dilemma and reach a general theory of biodynamics the molecule-contraction theory, as presented here and on some earlier occasions, was created. The essential aspect of the theory is the existence of "contractile" proteins, which also have the property of forming filaments. This theory is based on four premises, out of which three are supposed to be involved in all kinds of biodynamic activity, while the fourth is required only in those instances where polymerization and depolymerization is a constituent part of the performance of mechanical work. PMID- 1508989 TI - Electrical pulses appear in the inferior vena cava and abdominal aorta at contraction of leg muscles. AB - A vascular-interstitial neuromuscular closed circuit is described anatomically and electrically. The neuromuscular unit has a high resistance due to its axons. The "outer" vascular-interstitial branch has a low resistance due to a large cross section area. When a rat spontaneously contracts leg muscles after pinching a toe, electric potential pulses appear inside the inferior vena cava, between vena cava and peritoneum, between aorta and peritoneum, between vena cava and peritoneum and between aorta and subcutis. Minor pulses between electrodes in the peritoneal fluid are interpreted as induced by the intravascular potential pulses. The use of Ag-AgCl electrodes or platinum electrodes does not appreciably change the results. PMID- 1508990 TI - Potential differences in the inferior vena cava and between cava and extravascular electrode at leg contraction in man. AB - When a voluntary adult male contracted his leg muscles, electric potential differences were recorded between platinum electrodes positioned inside the vena cava or between the vena cava and the grounded skin. Two experiments confirm that potential differences at leg contractions in man have a similar appearance as those in the rat at pain-evoked contractions of leg muscles. Platinum electrodes were used in man. The potential differences obtained are thereafter compared with recordings with Ag-AgCl electrodes in salt-bridges in the rat. Slow potential waves with superimposed irregular potential oscillations are recorded in man as previously found in the rat using platinum or Ag-AgCl electrodes. The findings indicate that vascular-interstitial routes participate in a vascular-interstitial neuromuscular closed circuit, which is activated at contraction of the muscles. PMID- 1508992 TI - Contribution of paramagnetic trace elements of biological tissues to spin lattice relaxation times. PMID- 1508991 TI - Blood viscosity parameter correlation with types of leukemia. AB - We investigated the hemorheological, hematological and biochemical parameters in 30 cases of acute lymphocytic leukemia (ALL), 21 cases of acute myelogenous leukemia (AML) and 30 cases of chronic myelogenous leukemia (CML). The parameters studied include whole blood viscosity, plasma viscosity, erythrocyte sedimentation rate (ESR), red cell filterability, hematocrit, platelet count and aggregation, fibrinogen, hemoglobin, leucocyte count, bleeding time and lactate dehydrogenase activity (LDH). In the cases of ALL we observed significant decrease in whole blood viscosity, hemoglobin, hematocrit and platelet count but an increase in plasma viscosity, fibrinogen, bleeding time and LDH activity. In the cases of AML, we observed increase in whole blood viscosity, plasma viscosity, ESR, fibrinogen, leucocyte count, bleeding time and LDH activity but decrease in the hemoglobin, hematocrit and platelet count. In the cases of CML, we observed an increase of whole blood viscosity, plasma viscosity, ESR, fibrinogen elevation but decreases in bleeding time. In all cases, red cell filterability was unaffected. PMID- 1508993 TI - Localized and transient changes in plasma membrane fluidity during in vitro myoblast fusion: an 1H-NMR study. AB - High resolution proton NMR was used to study the cell surface molecular events which take place during in vitro myoblast differentiation and fusion. The CH3 and (CH2)n spectral signals were followed throughout in vitro myogenic development. The results show that although both the T1 and T2 relaxation times of the CH3 and (CH2)n groups are sensitive to the fusion process, T1 is the most sensitive. Both T1 of CH3 and (CH2)n increased before fusion indicating a higher degree of molecular motion and then returned to their original values. These results demonstrate how mobile lipid domains observed with proton NMR can be used to study the changes taking place during myoblast differentiation, particularly myoblast membrane fusion. PMID- 1508994 TI - Small acidic peptides from wheat germ chromatin. I. Isolation and biochemical characterization. AB - RNA synthesis in cell and cell-free systems is inhibited by a family of acidic, low molecular weight chromatin peptides (CPs). These peptides were extracted from deproteinized DNA of prokaryotic and eukaryotic cells, but the low yield of purified material by this procedure hinders efforts aimed at understanding their action mechanism in gene regulation. In this report we describe two purification methods of CPs from an easily available source, wheat germ. A comparison is made between the method starting from deproteinized DNA and the method from purified chromatin. The biological effects (inhibition of L1210 cell growth and DNA in vitro transcription) of CPs from wheat germ together with their chemical characteristics (molecular weight, amino acid composition and presence of phosphoserine) show strong homology with those of CPs from other sources. These results suggest a possible role of these chromatin peptides in controlling gene expression. PMID- 1508995 TI - No second thoughts here. PMID- 1508996 TI - ASPRSN involved in FDA hearings on breast implant issue. PMID- 1508997 TI - Reduction mammoplasty. AB - Breast reduction is a good example of the interface between aesthetic and reconstructive plastic surgery as both the breast size and eventual appearance of the breast change. Most patients are happy with their decisions to have the surgery for several reasons, including an appreciation of new clothing choices, improved self-image along with a disappearance of back pain and other physical symptoms associated with large, heavy breasts. PMID- 1508998 TI - The healing wound: clinical management. AB - Although research is actively seeking and may even be finding ways to reduce the time required for wounds to heal, the current state of the art is still moderated by correct assessment, appropriate interventions, and most of all, prevention of inhibiting factors that delay the healing process. PMID- 1508999 TI - Counseling the woman with silicone breast implants. AB - Public interest in silicone breast implants has heightened in recent months due to increased media hype that has included unscientific reviews and exaggerated accounts of a few women's problems. Lynne McCain, BSN, RN, of Emory Clinic's Section of Plastic and Reconstructive Surgery in Atlanta, provides common questions asked by patients with breast implants followed by appropriate responses that could be given in counseling. PMID- 1509000 TI - Stress: a self-management approach and nursing care plan for nurses. AB - Stress is unavoidable but can be controlled to provide the energy for health, growth, and the development of human potential. This article will overview stress and how it can be managed, and will present a care plan for self-management of stress. PMID- 1509001 TI - Disseminating plastic surgery information. PMID- 1509002 TI - Managing conflict. PMID- 1509003 TI - A death of a parent: one nurse's perspective. PMID- 1509004 TI - Setting up an operating room in an office setting. PMID- 1509005 TI - [The value of psychotropic drugs in treatment of suicidal behavior]. AB - There is no doubt about the importance of psychopharmacological medication- antidepressants, neuroleptics, tranquilizer--in the treatment of severe mentally ill people. In the last years there are a lot of publications dealing with psychopharmacological treatment of suicidal crises. Recently a few number of reports discuss the promotion of suicidality during or after start of antidepressant therapy. In this paper psychopharmacological medication, especially antidepressant medication is discussed according to suicide prevention or promotion. The author differentiate between acute suicidal crisis and long term treatment of an underlying mental illness and recommend in acute crisis treatment with benzodiazepines and sedating neuroleptics supplying adequate basic treatment. Uptonow to part of psychopharmaca in the treatment of suicidal patients remains uncertain. PMID- 1509006 TI - [The effectiveness of ambulatory occupational therapy measures for patients with schizophrenia]. AB - This study evaluates the concept of occupational therapy for schizophrenic outpatients. Preliminary results from 18 patients suggest that occupational therapy for outpatients might contribute to an improvement in cognitive-adaptive functions and open up ways for further integration on the job market. The prognosis was favourable when the outset of occupational therapy was not equated with a rise in the level of professional adaptation and a certain approachability and flexibility were to be observed in cognitive, affective and intentional aspects among the chronic schizophrenic patients. With regard to cognitive functions and to professional adaptation, it proved more favourable for occupational therapy to be carried out within the framework of regular service enterprises (external occupational therapy, n = 9) and not within training areas of the psychiatric institution itself (internal occupational therapy, n = 9). Patients taking part in internal occupational therapy felt more heavily burdened by workplace conditions, and greater family-related strain seemed to develop in the therapeutic centre than was the case among patients taking in external occupational therapy. PMID- 1509007 TI - [The symposium "Persecuted children and the children of the persecuted- psychological trauma over generations" 18-19 October 1991, University of Erlangen]. PMID- 1509008 TI - [Historical psychiatric miniatures. IV. A foster child of importance]. PMID- 1509009 TI - Mood influences on reasons for living in older adolescents. AB - Suicide is a major public health problem of the current period, particularly among young people, and is the second leading cause of death among the 15- to 24 year-old age group (Rudd 1989). Moreover, the suicide rate among the nation's youth has increased dramatically in the last two decades, an increase that amounts to having tripled in the years 1956 to 1975 (Holinger 1982). PMID- 1509010 TI - Relationships with patients in oncology: can a clinician be a friend? AB - Encounters with patients who are experiencing a life crisis such as cancer can be profoundly meaningful to both patients and those caring for them. Intense emotional involvement with patients can also lead to difficulties including "burnout" (Davitz and Davitz 1975), interstaff conflict (Burnham 1966; Pollack and Battle 1963; Robinson 1984; Weintraub 1964), and violation of professional boundaries (Applebaum 1990; Gartrell et al. 1986; Gutheil 1989a, 1989b). Nicholi (1988) has reviewed the challenges that psychotherapists face in maintaining relationships with patients that are both close and therapeutic. However, there has been little research into the relationships that clinicians in other medical disciplines have with their patients. This report describes both the stresses and rewards of relationships with oncology patients in a comprehensive sample of 192 staff members at a regional cancer center, interviewed about factors affecting their job satisfaction. PMID- 1509011 TI - Culture, social structure, and quandaries of psychiatric diagnosis: a Vietnamese case study. AB - In contemporary psychiatry diagnosis is arguably the most important concern of a clinical evaluation insofar as it operates as a scaffolding for therapeutic plans and recommendations. Implicit in the theory and lore of diagnosis is that disorders exist as naturalistic entities possessed of a distinctive form and course. In the event of a complex clinical presentation, a psychiatrist resorts to multiple diagnoses and the use of a rule-out diagnosis, (or several rule outs). The first practice reflects the dictum of comorbidity. Rule-out diagnoses, on the other hand, support the idea that in some instances extensive anamnesis, observation, and laboratory examination are required in order to establish the true identity of a clinical presentation. The way psychiatrists use the system of diagnosis when examining persons from their own society has been shown to reveal commonalities that conform to a systemic culture pattern (Fabrega et al. 1990a). With these subjects, then, our system of diagnosis works in the sense that it supports widely held assumptions and rationales. In this paper we present a case of a Vietnamese male patient. Its analysis from the standpoint of culture and social structure is used to illustrate some of the problems of reaching diagnoses in persons from other societies and the limitations of our theory about diagnosis. PMID- 1509012 TI - The mental health treatment team as a work group: team dynamics and the role of the leader. AB - Although treatment teams have been examined often in the mental health literature, this literature seldom addresses the crucial property of "teamness"- the key set of intangible phenomena that allow a team to function synergistically as more than the sum of its parts, and with a sense of team identity. In this paper, the concept of the work group is used to develop a framework for understanding the factors contributing to effective team functioning and identity, an their implications for the tasks of team leadership and sociotherapy: "the art of maintaining a social system in which the treatment of an individual patient can best occur" (Edelson 1970). Leadership activities that promote team cohesiveness and boundary maintenance are discussed, and suggestions are provided for ways in which the subjective experiences and emotional reactions of the leader and team members can be used to promote improved task performance and clinical care. PMID- 1509013 TI - Positive withdrawal and the quest for meaning: the reconstruction of experience among schizophrenics. AB - Psychosocial rehabilitation often remains entrapped within a restrictive definition. It is characterized by a normative orientation, which predetermines the objectives to achieve, and by an approach from outside of the person, which emphasizes the functional aspects of rehabilitation. In this context, marks of withdrawal, lack of involvement, or inactivity are interpreted as signs of passivity or as residual or negative symptoms, which are often associated with a negative prognosis. In parallel, as data regarding the heterogeneity of evolution of schizophrenia begin to accumulate, some authors have defended the idea that studies have to concentrate on the course of the disorder and on the associated processes (Harding et al. 1987; Strauss 1986). They propose going beyond an objective evaluation of signs and behaviors in order to situate them within a larger life-frame. This draws attention to the potential polysemy of symptoms, including the so-called negative symptoms, which can reflect a diversity of influences and therefore possess various psychiatric meanings (Strauss 1989). Yet, the systematic study of "meaning" in psychiatry is still in its infancy and lacks clear conceptual and methodological points of reference (Strauss and Estroff 1989). On another hand, implications for rehabilitation of a meaning centered approach to psychiatric symptoms have not been fully elaborated. An intensive study conducted in Montreal with patients diagnosed as schizophrenics sought to describe the factors and processes associated with different types of insertion in the community, and particularly to understand the rehabilitative strategies and the specific forms of being-in-the-world associated with an ability to remain in the community. Data collected through open-ended interviews were both quantitatively analyzed and subjected to content and qualitative analysis. The conceptual reference frame was derived from anthropology and from the European school of psychiatric phenomenology. Data indicate that non rehospitalization is associated with a stance of "positive withdrawal" (Corin 1990); it is characterized by a position at a distance from social roles and social relationships, combined with various strategies for keeping more tenuous links with the social environment. The case study presented here illustrates the complex organization of these various elements in a given life-frame. It also demonstrates the role played by symbols and meanings in developing a new articulation of personal experience. PMID- 1509014 TI - Making sense of delusions. AB - True delusions have been conventionally regarded as primary or psychologically irreducible (Jaspers 1913/1959) and thus only explicable in organic terms. While Jaspers acknowledged the existence of secondary delusions, which may be understood in the light of related affect, other experiences, or hallucinations, these were of lesser theoretical importance than true delusions, in which he found a change in "the totality of understandable connections." Anglo-American psychiatry, in espousing Jaspers and rejecting psychoanalysis, has in consequence concentrated on the form and not the sense of delusions. PMID- 1509015 TI - Late-onset atypical psychosis: a case involving neuroleptic drug toxicity and autoimmune serological abnormalities. AB - Serious or significant neuroleptic toxicity (Kurlan et al. 1984; Lazarus 1985; Levenson 1985; Pearlman 1986) may complicate the diagnosis and management of patients who develop acute medical problems while under treatment with neuroleptics (Levenson and Simpson 1986). We have found that in some cases it is difficult, if not impossible, to determine whether neuroleptics have contributed to the cause of an acute medical illness, or if the occurrence of acute medical problems precipitated the signs of neuroleptic toxicity by altering the disposition or the pharmacologic effects of the drugs. PMID- 1509016 TI - Cold hands and feet as a sign of abusive neglect in infants and children. PMID- 1509017 TI - The influence of sphincter control and genital sensation on body image and gender identity in women. AB - The development of one aspect of feeling female is hypothesized to account for certain phenomena in the treatment of young women patients. Fear of loss of genital pleasure experienced as contractions of the anal and genital-urinary sphincters is seen as the central issue in conflicts manifested in genital, oral, and anal modalities. It is suggested that the female's awareness of her genital arises from the generalization of sphincter sensation in the little girl, which is then represented in the body image. The body image is postulated as a link between genital pleasure and the valuing of femininity. PMID- 1509018 TI - Some vicissitudes of aggression in the interpretive process. AB - Interpretation is a product of compromise formation that requires optimal use of the analyst's aggression to be an effective analytic intervention. Aggressive aims useful for the interpretive act are problematic for analysts and have led both to clinical difficulties and to various theoretical reactions against considering interpretation essential for analytic progress. In analysis, diverging aims of analyst and patient are highlighted in connection with the analyst's function as interpreter. The interactions between patient and analyst pertaining to interpretation provide insights into the patient's intrapsychic conflicts that may be less apparent in other material. PMID- 1509019 TI - The wish to be soothed as a resistance. AB - As the analyst makes the correct interpretations of resistance in the opening phase of an analysis, the patient begins to feel understood, often for the first time. This feeling allays anxiety and depressive affects, and the patient comes to experience the analyst as a soother. These initial exchanges may lay the foundation for a positive transference which acts as a buffer against turbulent transferences. In some patients this positive transference develops rapidly, often with prompt symptom remission. In others--children as well as adults--the analyst must persistently interpret defensive regressions before a stable, positive transference can emerge. In either case, in order to avoid the analysis of conflict, some patients become resistant to the analysis of the wish to be soothed. Many of these patients have had a childhood filled with traumatic parental stimulation or rejection. Two clinical accounts illustrate these contentions. PMID- 1509021 TI - The psychoanalytic view of phobias. Part IV: General theory of phobias and anxiety. AB - This is the final part of the work on the psychoanalytic view of phobias. Here we consider general views of phobias, developments and issues in the psychoanalytic theory of anxiety, as it relates to phobias, and take up aspects of some broader theoretical issues, including nosology. PMID- 1509020 TI - The psychoanalytic view of phobias. Part III: Agoraphobia and other phobias of adults. AB - This is the third part of a review and commentary on the psychoanalytic literature on phobias. This section takes up agoraphobia and other phobias of adults, and suggests further avenues for interpenetration of psychoanalytic and psychiatric approaches. PMID- 1509022 TI - Temporal-order judgment and reaction time for short and long stimuli. AB - The effect of intensity on visual latency was investigated. Visual latency was measured by two methods: simple motor reaction time (RT) and temporal-order judgment (TOJ). It was found, in accordance with previous studies, that the changes in RT were larger than TOJ latency when measured in the same range of intensity. Moreover, the relationship between TOJ latency and intensity was compared in two conditions: under so-called "with-offset", the information about offset order was available for the subject, while under "without-offset" conditions it was not. It was hypothesized on the ground of Jaskowski's 1991 study that the TOJ latency-intensity relation should differ for these two conditions because of the effect of intensity on visual persistence. We were unable to find any such effect. PMID- 1509023 TI - Optical magnification as event information. AB - The geometrical optics of approach events is delineated. It is shown that optical magnification provides information about distance and time until collision. An experiment is described in which two objects--white styropor spheres 10 cm in diameter, seen against a white plaster wall--were moved simultaneously at equal, constant speed along straight, converging paths at eye level towards a human observer and towards a common, virtual point of collision which either coincided with the observer's station point or was placed in front of, or behind, that point. Approach events differed with regard to trajectories, distances, velocities, and times-to-collision involved. Events were observed monocularly fixating and binocularly non-fixating, without head movements. The objects always stopped before colliding, and subjects had to respond to the virtual collisions. Most responses were too early, especially for impending collisions at, or behind the observers' station point. Responses for impending collisions in front of the observers tended to be too late, especially for larger total amounts of optical magnification and higher velocities, which together imply shorter times-to collision. Relative errors were comparatively larger for very short and very long times-to-collision throughout, where events of the first kind were overshot, the latter ones undershot. Results are interpreted with reference to biological theories and the constraints imposed by geometrical optics. Special attention is focused on the issue of unavoidable, necessary confounding of variables in time to-collision studies. PMID- 1509024 TI - The tunnel effect, Gibson's perception theory, and reflective seeing. AB - Subjects can have continuous visual experience of an object's movement across a display though the movement's middle phase takes place behind an opaque screen. The present article considers explanatory issues pertaining to this so-called, tunnel effect, with special reference to Gibson's perception theory and the visual activity that I have been calling reflective seeing. Among the issues discussed are the following. (a) In the tunnel experiments, I suggest, there occur both persisting perception, as Michotte held, and persistence perception, as Gibson held. The subjects pick up stimulus information that allows visually experiencing the object's going out of sight at one edge of the screen and coming back into sight at another edge of the screen; the subjects have visual experience of the continued existence and movement of the object while it is out of sight. Moreover, persistence of perceptual experience is involved: when the object goes out of sight, the subjects' visual experience of its movement goes on. (b) I also argue that the tunnel effect is a phenomenon of both straightforward and reflective seeing. Adopting a phenomenal attitude, as one does when reporting one's perceptual experience, one still sees movement taking place on the other side of the screen, as one does in straightforward seeing. However, whereas straightforward seeing does not give inner awareness of visual experience, the subjects in the tunnel experiments report visually experiencing the object's movement while also visually experiencing the opaque screen in front of it as opaque. I argue that these reports, and those about the object's going out of and coming back into sight, must be based on the kind of visual experience that is part and product of reflective seeing. PMID- 1509025 TI - Analog versus discrete shifts of attention across the visual field. AB - Two discrimination experiments were run to investigate analog versus discrete properties of a shift of visual spatial attention. Central cuing was used in Experiment 1, whereas peripheral cuing was used in Experiment 2. Presentation of a probe stimulus between fixation and the target (Distance 1), opposite fixation from the target (Distance 3), or away from an imaginary line running from the target through fixation (Distance 2) permitted a fine-grained analysis of attention at those loci across target-probe delays. D-prime analyses in both experiments suggest that attention is shifted in a discrete manner between locations. Sensitivity to probes was generally greater when the probe was aligned with the target and fixation, with Distance 3 equal to Distance 1, than when it was away (at Distance 2). Analysis of sensitivity to targets across cue-probe delays suggests that attention was directed to the probe upon its appearance. PMID- 1509026 TI - Impaired student nurses. PMID- 1509027 TI - [Integrated imaging of head and neck tumors in children]. AB - Examinations of 28 children with various tumors of the visceral cranium and neck have shown that both ultrasound and magnetic resonance tomography should be used primarily for diagnosis and follow-up. These tomographic methods are especially suitable for use in children. Ultrasound is better suited to visualization of localized, superficial masses and MRT to examination of deeper lying tumors within the complex structures of the visceral cranium and neck. X-rays in different planes should be regarded as supplementary examinations. The use of CT, preferably as high-resolution CT, provides more precise visualization of fine bone structures. Conventional tomography has been almost completely replaced by CT. Angiography is applied mainly in subsequent, interventional measures; videofluoroscopy should be used to examine lesions of the upper airways and digestive tract. PMID- 1509028 TI - [Indications for magnetic resonance tomography of abdominal space-occupying lesions in children]. AB - The frequency of magnetic resonance imaging for investigation of abdominal tumors in childhood is increasing. Malignancies of the liver can be visualized. For benign lesions the accuracy is high particularly in the case of hemangiomas. Magnetic resonance investigations are advisable in the presence of abdominal tumors, in order to differentiate lymph nodes and vascular involvement. Magnetic resonance imaging is mandatory in the case of retroperitoneal and presacral masses to depict any intraspinal tumor spread. RARE myelography can replace computed tomography myelography. PMID- 1509029 TI - [Characteristics of thyroid sonography in infants and children]. AB - In a prospective study the thyroid glands of 598 healthy boys and girls (newborn to 17 years old) were examined by ultrasound. The volume of the normal gland was 1.1 cm3 in neonates, 2 cm3 in 4 year-old-children, and 8.7 cm3 in schoolchildren. The gland of a normal newborn, a girl with congenital hypothyroidism, a girl with inflammation of a median cervical cyst, a girl with insulin-dependent diabetes mellitus and autoimmune thyroiditis, and a girl with an adenoma all showed typical differences in ultrasonic structure from the normal adult gland. Sonography of the thyroid gland discloses valuable information, especially in childhood. PMID- 1509030 TI - [Aluminum poisoning caused by the phosphate binder in a non-dialysed child with chronic renal insufficiency]. AB - In patients with chronic renal failure, aluminium, which is included in the dialysate or released from phosphate binders, cannot be eliminated adequately. It forms a deposit in the tissues and leads to intoxication. After a 6-month therapy with aluminium-containing phosphate binders in a non-dialysed baby with chronic renal insufficiency, an osteomalacia arose with distinct subepiphyseal and metaphyseal changes attributable to disorders of mineralization. The consequence of this was a "bone-within-bone" appearance and pathological fractures. After a change of therapy, the bone alterations receded within a few months. Simultaneously, the distinctly elevated serum level of aluminium fell. Therefore, aluminium should be avoided in non-dialysed children with chronic renal insufficiency. PMID- 1509031 TI - [Diagnosis of complications of ventriculo-peritoneal and ventriculo-atrial shunts]. AB - The value of imaging (cranial CT, cranial and abdominal sonography, plain film surveys) was examined retrospectively in 28 shunted children in whom 82 instances of suspected dysfunction arose. There were 23 obstructions, 12 dislocations, 1 disconnection, 6 infections, 3 overdrainages and 5 slit ventricle syndromes. Impaired absorption with ascites, a peritoneal liquor cyst and a seroma occurred in the peritoneal part of the shunt. Progressive dilatation of the ventricle system shown by CCT (89%) or ultrasound was the most sensitive sign of high pressure hydrocephalus. Periventricular hypodensity and flattening of the gyri (15%) were found less often. An examination strategy in suspected shunt dysfunction is suggested on the basis of these findings. PMID- 1509032 TI - [Digital luminescence radiography of premature and term infants. Possibilities and limitations]. AB - Postmortem images of seven premature and term newborns, acquired with various conventional screen-film combinations and by a digital technique with appropriate radiation exposures, were compared. Images without and with simulated pathology were used in this study. With electronic manipulation of the computed radiographs we obtained well-balanced images with good contrast, and in many cases the artifacts were better visualized than with the conventional screen film. However, in our study no significant dose reduction for this young age group was possible with the digital technique compared with conventional screen film. PMID- 1509034 TI - [An infiltrate of unclear origin in the right mid-field. Embolism of the right pulmonary artery with a hemorrhagic pulmonary infarct]. PMID- 1509033 TI - [Magnetic resonance tomographic diagnosis of internal lesions of the shoulder following luxation. A comparison with arthroscopic findings]. AB - Fifteen patients with a recurrent dislocation of the glenohumeral joint were preoperatively investigated by MRI. We created a special protocol with axial T1-, T2-, proton-density- and sagittal T1-weighted images. MRI findings such as defects of the glenoid labrum and Hill-Sachs compression fractures proved to be correct during surgery. In the chosen protocol the diagnostic imaging of rotator cuff lesions was not specific. In 10 cases lesions were seen but in only 5 patients did these findings prove to be correct during surgery. However, MRI imaging of glenohumeral joints is a reliable non-invasive diagnostic method. PMID- 1509035 TI - Questions regarding the treatment of localized prostate cancer. PMID- 1509036 TI - Primary aldosteronism: an endocrine perspective. PMID- 1509037 TI - Intussusception in children: the role of sonography. PMID- 1509038 TI - Careers for a lifetime: the role of continuing medical education. PMID- 1509039 TI - Ovarian cysts: will transvaginal alcohol sclerosis help postmenopausal women? PMID- 1509040 TI - Clinical epidemiology and radiology: the need to bridge the gap. Breast screening: a case study. PMID- 1509041 TI - Analysis of cancers missed at screening mammography. AB - Analysis of 320 cancers found in a screened population between August 1985 and May 1990 revealed 77 cancers that were "missed" at screening mammography. The missed lesions consisted of cancers incorrectly diagnosed after mammography (false-negative results) but visible in retrospect (n = 19); cancers correctly diagnosed after mammography but visible in retrospect on an earlier mammogram (n = 47); and cancers that went undetected by the first of two readers (n = 11). Missed lesions were categorized according to type of miss, reason for the miss, breast density, lesion features, and lesion location. The missed lesion were compared with 121 cancers that were correctly diagnosed at screening mammography. The missed cancers occurred in women with denser breasts (P = .046), were less likely to demonstrate malignant microcalcifications, and were more likely to demonstrate a developing opacity as an indication of cancer (P = .005). An understanding of the characteristics of missed lesions may be a valuable aid in increasing the sensitivity of screening mammography. PMID- 1509042 TI - Reading and decision aids for improved accuracy and standardization of mammographic diagnosis. AB - Image-reading and decision aids were designed to improve the accuracy of mammogram interpretation. The reading aid was a list of diagnostic radiographic features and scales for quantification of each feature. The decision aid, a computer program, converted the reader's scaled values, weighted for predictive power, into an advisory estimate of the probability of malignancy. The features were identified and their importance was assigned in four steps: (a) interviews of five expert readers to establish an initial set of features, (b) perceptual tests to refine the feature set, (c) a consensus meeting to refine this set and establish nomenclature and scales, and (d) the expert's scaling of each feature in a set of 150 mammograms. Those scaled judgments were analyzed to provide the final list of features and their relative importance and to program the computer decision aid. To test the enhancement effect, six other radiologists interpreted a different set of mammograms without, and later with, the two aids. Receiver operating characteristic analysis showed a gain of approximately 0.05 in sensitivity or specificity when the other value remained at 0.85. In a subset of the more difficult cases, the enhancement effect was approximately 0.15 in either sensitivity or specificity. PMID- 1509043 TI - A comparison of mammography screen-film combinations. AB - A comparison study was performed to evaluate the image quality and radiation dose of six mammographic screen-film combinations: a Min-R screen with OM-1, SO-155, and SO-177 films (Eastman Kodak); a Min-R medium screen (Eastman Kodak) with OM-1 film; an HR Mammo medium screen (Fuji Medical Systems USA) with OM-1 film; and a Min-R fast screen with T-Mat M II film (Eastman Kodak). SO-177 films were processed with an extended cycle. Exposures of an acrylic test object with embedded masses, fibers, and specks and of a preserved breast specimen were made, for two paired image comparison tests in which the visibility of diagnostic features, contrast, and noise were judged. In most areas of image quality evaluated, a Min-R screen with OM-1, SO-155, and SO-177 films was superior. These three screen-film combinations had similar imaging characteristics, even though OM-1 film requires a higher radiation exposure. Images produced with a Min-R fast screen and T-Mat M II film were significantly lower in quality. PMID- 1509044 TI - MR relaxometry imaging. Work in progress. AB - Acquisition of relaxation rate dispersion curves from magnetic resonance images was demonstrated on a clinical, whole-body imaging system. Study of the behavior of relaxation rates over a range of field strengths probes the structural environment of imaged hydrogen protons and reveals information about the composition of tissue. The authors determined relaxation rates in extremities and heads of healthy volunteers. The sensitivity of the measurement is sufficient to obtain a distinctive relaxation rate dispersion behavior for different tissues. PMID- 1509045 TI - New relative-value scale for Medicare: an update. PMID- 1509046 TI - Animal rights and research: common sense must prevail. AB - The advances that radiologic science has experienced in recent history have been earned through many means, one of them being animal research. Since the 1980s, animal research has come increasingly into the public eye, through the efforts of animal welfare and animal rights activist groups. These groups, by their varied means, have exacted changes in how animals are used experimentally and how the public perceives such use. In some cases, their lobbying efforts have resulted in laws that raise the cost of research and provide little improvement in animal welfare. Because of the financial and political power of these groups and the increasing public awareness of such issues, it is extremely important that the medical and scientific communities become more involved in educating the public on the importance of animal research and clarifying the difference between animal welfare and animal rights. Equally important, the medical community must continue to adhere to high standards in research that involves animals. PMID- 1509047 TI - Simple adnexal cysts: the natural history in postmenopausal women. AB - Transabdominal and transvaginal ultrasound (US) examinations were performed in 184 asymptomatic postmenopausal volunteers to determine prospectively (a) the frequency and natural history of simple adnexal cysts in healthy postmenopausal women and (b) the relationship between cyst activity and both hormone replacement and length of time since menopause. Eighty-three simple adnexal cysts were found in 52 women. Thirty-two of 184 women (17%) had 37 cysts identified at initial examination; 46 new cysts appeared in 31 women (11 of whom previously had cysts). Forty-nine women with 72 cysts were reevaluated with subsequent US scanning over a period of 3-23 months. Thirty-eight of the 72 cysts (53%) disappeared completely, 20 (28%) remained constant in size, eight (11%) enlarged by 3 mm or more, two (3%) decreased in size by 3 mm or more, and four (6%) both increased and decreased in size on repeated examinations. No statistical relationship was found between presence of cysts or cyst activity with respect to the type of hormone replacement or length of time since menopause. PMID- 1509048 TI - Ovarian cysts in postmenopausal women: preliminary results with transvaginal alcohol sclerosis. Work in progress. AB - Seven patients with a recurrent ovarian cyst after transvaginal needle aspiration underwent alcohol sclerosis of the cyst. The cysts had the appearance of simple cysts at ultrasound (US). Sclerosis, an outpatient procedure, was performed with a transvaginal approach under continuous endovaginal US guidance. After aspiration of the cyst contents, approximately two-thirds of the aspirated fluid was replaced with 100% alcohol that was left in place for 20 minutes and then aspirated. No complication was observed. Four cysts had not recurred at follow-up examinations performed 2, 5, 7, and 12 months, respectively, after sclerosis. One patient underwent surgery because mucinous material was found on analysis of the specimen, which was proved to be a benign cystadenoma. The two other cysts recurred, and one patient underwent surgery. Alcohol sclerosis of ovarian cysts may have a role in the treatment of postmenopausal women with ovarian cysts with a low risk of malignancy. PMID- 1509049 TI - Distinction between hyperaldosteronism due to bilateral hyperplasia and unilateral aldosteronoma: reliability of CT. AB - Hyperaldosteronism due to a unilateral adenoma must be distinguished from hyperaldosteronism due to bilateral hyperplasia to enable the proper choice between surgical treatment (for adenoma) or medical treatment (for hyperplasia). To compare the efficacy of computed tomography (CT) and adrenal venous sampling, both examinations were performed in 24 patients with primary aldosteronism. All patients with a diagnosis of adenoma based on findings at venous sampling underwent adrenalectomy. The CT-based diagnosis was unilateral aldosteronoma in 17 patients and hyperplasia in seven patients. On the basis of venous sampling, unilateral adenoma was diagnosed in 22 patients; this diagnosis was confirmed by means of unilateral adrenalectomy in 21 patients. The most common error was diagnosis of hyperplasia based on the presence of bilateral nodules on CT scans: In six of seven patients with such a diagnosis, venous sampling and subsequent surgery revealed a unilateral adenoma. In hyperaldosteronism with multiple bilateral nodules, CT cannot reliably permit distinction between hyperplasia and adenoma. PMID- 1509050 TI - Venocclusive disease of the liver: prospective study of US evaluation. AB - Twenty-one bone marrow transplantation (BMT) patients were studied prospectively to determine the prevalence of sonographic hepatobiliary abnormalities and to determine if these abnormalities were associated with hepatic venocclusive disease (VOD). Baseline US was performed in all patients prior to chemoradiation therapy, with follow-up ultrasound (US) examinations at the time of BMT and 14 days and 28 days after BMT. Sonograms were reviewed for the presence of ascites, gallbladder wall thickening, hepatosplenomegaly, hepatofugal flow, hepatic vein compression, increased periportal echogenicity, and increased hepatic echotexture. The baseline scans showed 13 of 21 patients (62%) with abnormalities prior to BMT. Within 2 weeks after BMT, serial US showed interval development of hepatomegaly in five patients (three with VOD and two without), gallbladder wall thickening in one (with VOD), hepatic vein compression in two (both with VOD), hepatofugal flow in one (without VOD), and ascites in one (with VOD). US scans obtained 4 weeks after BMT in 15 of the 21 patients showed even fewer new abnormalities. No sonographic finding was strongly associated with VOD. PMID- 1509051 TI - Hepatic metastases from colorectal cancer: influence of hepatic volumetric analysis on surgical decision making. AB - A prospective study was performed to determine the impact of preoperative assessment of estimated postoperative liver volume on surgical decision making for liver metastases from colorectal cancer. Assessment of estimated postoperative liver volume was performed before surgery in 25 patients. Mean estimated postoperative liver volume +/- standard deviation (SD) was 697 cm3 +/- 317 (range, 320-1,532 cm3). Mean relative estimated postoperative liver volume +/ SD was 51% +/- 16 (range, 20%-90%). In two patients, relative estimated postoperative liver volumes of less than 35% prevented resection. These two patients underwent preoperative portal vein embolization, which resulted in marked hypertrophy of the unembolized healthy part of the liver and subsequent safe resection. Before surgery, all patients had a relative estimated postoperative liver volume of greater than 35%, and no cases of postoperative liver failure occurred. The results demonstrated that assessment of estimated postoperative liver volume provides vital preoperative data for reducing the risk of postoperative liver failure. PMID- 1509052 TI - Focal nodular hyperplasia of the liver: MR imaging and pathologic correlation in 37 patients. AB - Thirty-seven patients with 48 lesions of focal nodular hyperplasia (FNH) underwent preoperative magnetic resonance (MR) examination and surgical resection. Sixteen lesions were imaged at 0.5 T with T1- and T2-weighted spin echo sequences; 32 lesions were imaged at 2 T with T1-and T2-weighted spin-echo and gradient-recalled-echo sequences. Contrast material-enhanced MR imaging was performed in 20 lesions. MR imaging failed to depict six tumors that were less than 3 cm in diameter. Typical appearance was present in 18 of the 42 (43%) lesions seen at MR. Atypical lesion features included no scar (n = 15), hypointense scar on T2-weighted images (n = 7), pseudocapsule (n = 6), strong hyperintense lesion on T2-weighted images (n = 3), diffuse hyperintensity on T1 weighted images (n = 3), and heterogeneous lesion (n = 1). Comparison between findings at MR imaging and at histopathologic examination was performed in 38 lesions: There was good correlation between presence and size of the scar on both examinations. In 13 of 20 (65%) of the hyperintense scars on T2-weighted images, edema was prominent, whereas in five of the seven (71%) hypointense scars on T2 weighted images, edema was absent or low. PMID- 1509053 TI - Unilocular hydatid liver cysts: treatment with US-guided, double percutaneous aspiration and alcohol injection. AB - Sixteen hydatid liver cysts in 14 patients were treated with a percutaneous double puncture-aspiration-injection (D-PAI) technique with alcohol used as the scolecidal agent. With ultrasound guidance, fine-needle drainage of cysts was performed, and 95% sterile alcohol was injected and left in situ to partly refill the cystic cavities. The same procedure, without reaspiration of the injected alcohol, was performed 3 days later. Viability of scoleces was assessed at each aspiration. Benzoimidazolic drugs were administered 1 week before and 3 weeks after the procedure, to reduce the risk of seeding scoleces. Follow-up ranged from 8 to 28 months (mean, 14 months). Six cysts disappeared within 40-75 days of completion of D-PAI. In the other patients, smaller liquid areas or hypo- or hyperechoic solid masses were observed. Anaphylactoid reactions did not occur. In one patient, a biliary fistula developed after the first aspiration; the second ethanol injection was postponed until 6 months later but was effective. Viable scoleces were found at the second aspiration in only two patients whose hepatic liver cysts completely healed. Serologic titers substantially decreased in seven cases and became negative in two. PMID- 1509054 TI - Hepatosplenic schistosomiasis: comparison of sonographic findings in Brazilian and Sudanese patients--correlation of sonographic findings with clinical symptoms. AB - Twenty-seven Brazilian and 32 Sudanese patients with hepatosplenic schistosomiasis from areas where the disease is endemic were examined with ultrasound (US). Hyperechoic periportal areas indicating periportal fibrosis (PPF) were present in all patients irrespective of their origin. Nonspecific findings were splenomegaly (all patients), gallbladder wall thickening (81% and 92%, respectively, in Brazilian and Sudanese patients), portal vein (74% and 87%, respectively) and splenic vein (59% and 70%, respectively) enlargement, and portosystemic vascular shunts (62% and 61%, respectively). The hepatic alterations were congruent and the frequency of their occurrence was similar in both patient groups. With a standardized grading system, it was shown that grade of PPF was significantly correlated with a history of bleeding from endoscopically proved esophageal varices and with distention of the portal vein as measured with US. It was concluded that sonographic grading may be used in patients with hepatosplenic Schistosoma mansoni infection who originate from completely different endemic areas. PMID- 1509055 TI - Measurement of tissue carcinoembryonic antigen levels from fine-needle biopsy specimens: technique and clinical usefulness. AB - Levels of tissue carcinoembryonic antigen (CEA) in 54 abdominal fine-needle biopsy specimens from 50 patients were measured to ascertain the use of tissue CEA levels in diagnosis of malignancy. Biopsy was performed in the following sites: liver (n = 34), retroperitoneum (n = 8), adrenal gland (n = 3), pancreas (n = 2), omentum (n = 2), pelvis (n = 2), spleen (n = 2), and stomach (n = 1). Histologic findings proved malignancy in 39 patients and benign disease in 11 patients. In these 11 patients, the mean levels of tissue CEA were lower than the normal level of serum CEA (3 ng/mL). Tissue CEA levels were higher than serum CEA levels in nine patients with colonic carcinoma and in 12 of 16 patients with noncolonic CEA-secreting malignancies. Four patients with noncolonic CEA secreting malignancies had tissue CEA levels within the normal range (less than 3 ng/mL). Tissue CEA levels were also normal in 13 patients with various non-CEA secreting tumors. Tissue CEA levels may prove useful in biopsy of necrotic or cystic lesions and assessment of response to ablative therapy for colon metastases. PMID- 1509056 TI - Transnasal US of the esophagus: preliminary morphologic and function studies. AB - High-frequency catheter-based ultrasound (US) transducers can be inserted into the esophagus transnasally to evaluate esophageal wall structures. Studies were performed in two sheep esophagus specimens in vitro, in 17 healthy human subjects, and in 16 patients with esophageal abnormalities (eight with achalasia, four with scleroderma, three with esophageal carcinoma, and one with esophagitis). In the sheep specimens, endoluminal US delineated seven layers of the esophageal wall; these results correlated closely with histologic findings. Real-time US of the normal esophageal wall was performed during resting and swallowing. Muscles at the lower esophageal sphincter (LES) were shown to be thicker than muscles in the body of the esophagus. Thickening of the muscular layers at the LES in achalasia, dilated blood vessels within the submucosa in esophagitis, and fibrotic changes within the muscular layers in scleroderma were demonstrated. Extramural structures adjacent to the esophagus were also seen. These preliminary results suggest that transnasal esophageal US may become an important diagnostic tool in evaluation of the esophagus. PMID- 1509057 TI - Esophageal strictures: treatment with a new design of modified Gianturco stent. Work in progress. AB - To overcome the drawbacks of the modified Gianturco stent tube with barbs, a new barbless stent tube was constructed. Twenty-two barbless stent tubes 4.5-14.0 cm long were placed with a new introducing tube in 21 patients: 10 stent tubes in 10 patients with recurrent dysphagia after radiation therapy or chemotherapy, 10 in 10 patients with esophageal cancer in whom surgical management was contraindicated, and two in one patient with postoperative benign stricture. No technical failure or procedural complications occurred. After the procedure, all but two patients could ingest most or all foods. In two patients with an esophagorespiratory fistula and one patient with esophageal rupture, the barbless stent tube successfully occluded the fistula and rupture site. The stent tube migrated in one patient. Fifteen patients are surviving, with the stent tubes patent for 3-35 weeks (mean patency, 13 weeks); the six other patients died 7-24 weeks (mean, 16 weeks) after stent placement. It is concluded that barbless stent tubes show promise in the management of dysphagia caused by esophageal strictures. PMID- 1509058 TI - Optimizing gallbladder stone lithotripsy: an international survey. AB - Rates of stone clearance with extracorporeal shock wave cholecystolithotripsy (biliary lithotripsy [BL]) initially reported by European groups were encouraging. An American multicenter BL study (the Dornier National Biliary Lithotripsy Study [DNBLS]) did not reproduce these results. The BL treatment strategies and 6-month stone clearance rates of six leading European and Japanese centers were compared with those of DNBLS. All foreign centers used adjuvant oral chemolitholysis and greater shock wave energies from the same lithotriptor as that in DNBLS. Six months after BL, the stone clearance rates at all six centers were higher than those of DNBLS. There were no significant differences in complication rates between centers. These findings suggest that the poor results of DNBLS were chiefly due to the use of low kilovoltage and few BL sessions. Increased energy levels and a fragment size end point of less than 5 mm optimize BL. Despite the popularity of laparoscopic cholecystectomy, BL can be recognized as a successful treatment alternative for patients with a low burden of radiolucent stones. PMID- 1509059 TI - Intussusception in children: reliability of US in diagnosis--a prospective study. AB - To assess the diagnostic value of ultrasound (US) in clinically suspected acute intestinal intussusception in children, the authors prospectively compared US and enema studies in 83 episodes. None of the cases negative at US proved to be intussusception at enema study (negative predictive value = 100%). The sensitivity of US was 100%, and the specificity was 88%. Most of the sonograms were initially obtained and examined by residents. Several unsuspected abnormalities were also found with US. The authors conclude that a few months of training in US appears to be sufficient for high-accuracy investigation of clinically suspected intussusception, enabling selection of those patients in need of an enema. PMID- 1509060 TI - Appendicitis in children: color Doppler sonography. AB - The authors used color Doppler ultrasonography (US) to evaluate 33 children with suspected appendicitis and found locally increased blood flow in all of 10 patients with appendicitis or periappendiceal abscess; the studies were normal in 16 patients without appendicitis. The gray-scale sonographic results were concordant in all 26 of these patients. In two other patients with presumptive mesenteric adenitis and in one patient with a hemorrhagic ovarian cyst at gray scale US, color Doppler imaging showed no increased perfusion and aided in confirming the absence of a significant inflammatory process. In four other children, color Doppler US clarified gray-scale sonographic findings that might have been confused with complicated appendicitis and aided in the diagnosis of other causes of acute abdominal pain. These findings indicate that color Doppler US is a useful adjunct to gray-scale US in evaluating children with suspected acute appendicitis. PMID- 1509061 TI - US measurement of the subarachnoid space in infants: normal values. AB - The subarachnoid space was examined with real-time ultrasonography (US) in 89 healthy infants. US of the brain in all infants revealed no abnormalities. Three variables were measured in the coronal plane at the level of the foramen of Monro: the sinocortical width (SCW) ranged from 0.4 to 3.3 mm, the craniocortical width (CCW) from 0.3 to 6.3 mm, and the interhemispheric width (IHW) from 0.5 to 8.2 mm. All variables can be used routinely, as the SCW could be demonstrated in all infants, and the CCW and IHW were demonstrated in 96% (85 of 89). Correlation of sonographic measurements with the independent variables age, head circumference, body weight, and body length was poor. To differentiate normal from pathologically dilated subarachnoid spaces, the following upper limits are proposed on the basis of the 95th percentile: 3 mm for SCW, 4 mm for CCW, and 6 mm for IHW. PMID- 1509062 TI - Enhanced detection of vesicoureteral reflux in infants and children with use of cyclic voiding cystourethrography. AB - Cyclic voiding cystourethrography (VCUG) was prospectively evaluated to determine its ability to demonstrate vesicoureteral reflux (VUR) in children whose VCUG results were initially negative. The authors also assessed the effect of change in the patient's position on the detection of VUR. Seventy-seven children younger than 3 years of age, with negative results from a VCUG study performed while they were supine, underwent a second cycle of bladder filling after they were placed prone (group 1). Sixty-five children who were also younger than 3 years of age and had negative results from an initial VCUG examination performed in the usual supine position underwent a second cycle of bladder filling, which was also performed with the patient supine (group 2). VUR occurred in three children (4%) in group 1 and in eight (12%) in group 2. Most children (68.8%) in the two groups combined had grade II reflux. Cyclic VCUG increased detection of VUR, which led to a change in clinical treatment. Prone positioning did not enhance detection of VUR to the same degree as did multiple studies performed with the patient supine. PMID- 1509063 TI - Paranasal echogenic mass: sonographic sign of bilateral complete cleft lip and palate before 20 menstrual weeks. AB - A paranasal echogenic mass identified at ultrasound performed during the second trimester was the initial and primary clue to the presence of bilateral complete cleft lip and palate in four fetuses. Referral had been for dating purposes in three cases and because of high maternal serum alpha-fetoprotein level in one. Genetic amniocentesis revealed deletion of the 15th chromosome in one case. The clefts were small and difficult to visualize; the finding of the echogenic mass (representing a premaxillary protrusion) therefore added confidence to the diagnosis. PMID- 1509064 TI - Spectrum of salivary gland disease in HIV-infected patients: characterization with Ga-67 citrate imaging. AB - The authors retrospectively reviewed 45 gallium-67 citrate scans of 28 patients infected with the human immunodeficiency virus (HIV). Abnormal salivary gland radiotracer activity was seen in 13 patients with diffuse infiltrative lymphocytosis syndrome (DILS), five patients with undifferentiated salivary gland disease (USD), and 10 patients with acquired immunodeficiency syndrome (AIDS). More DILS patients (54%) had intense gallium uptake than did the AIDS and USD patients combined (13%) (P less than .05). DILS patients had markedly elevated CD8 cell counts and moderately reduced CD4 cell counts, while AIDS patients had normal CD8 cell counts and markedly reduced CD4 cell counts. These differences were statistically significant (P less than .05). The authors recommend that DILS be considered in the differential diagnosis when abnormal, particularly intense, bilateral salivary gland gallium uptake occurs in HIV-infected patients. This disease is more likely to occur when circulating CD8 lymphocytosis is present, while AIDS is the more likely diagnosis when the patient has a normal CD8 cell count and a markedly depressed CD4 cell count. PMID- 1509065 TI - Postoperative diskitis: distinguishing early MR imaging findings from normal postoperative disk space changes. AB - To distinguish early magnetic resonance (MR) imaging findings in postoperative diskitis from normal postoperative changes, a prospective study was performed in 15 asymptomatic patients (17 disk levels) who underwent uncomplicated lumbar diskectomy and seven patients with proved postoperative diskitis. On postoperative MR images, four of the asymptomatic patients had a finding that could also be seen in patients with diskitis. Gadolinium enhancement was useful in making the distinction and occurred as follows: (a) vertebral bone marrow: all seven diskitis patients and one asymptomatic patient; (b) disk space: five diskitis patients and three asymptomatic patients; and (c) posterior anulus fibrosus: all seven diskitis patients and 13 asymptomatic patients (14 of 17 levels). This entire triad of findings, which is strongly suggestive of postoperative diskitis, was not seen in any of the asymptomatic patients. Changes in the disk space and adjacent bone marrow on pre- and post-contrast MR images after routine diskectomy are uncommon and should not be assumed to be normal postoperative changes without careful consideration and analysis for early diskitis. PMID- 1509066 TI - Moyamoya disease: diagnosis with three-dimensional time-of-flight MR angiography. AB - Twelve patients with moyamoya disease were studied with three-dimensional time-of flight magnetic resonance (MR) angiography, and the findings were compared with results obtained with conventional arteriography. Of a total of 24 supraclinoid internal carotid arteries studied, 21 arteries (88%) were accurately evaluated with MR angiography and in three arteries the extent of occlusive disease was overestimated. Of a total of 72 large branch basal cerebral vessels, including the bilateral anterior, middle, and posterior cerebral arteries, 61 arteries (85%) were accurately evaluated with MR angiography and in 11 arteries the extent of occlusive disease was overestimated. While conventional arteriography showed basal cerebral moyamoya vessels in all 24 hemispheres, MR angiography showed moyamoya vessels in 20 of these. Of a total of 28 large leptomeningeal and transdural collateral vessels, 18 were identified with MR angiography. In the one surgical collateral vessel evaluated, MR angiography successfully showed its patency. MR angiography may have value in following disease progression and, perhaps, in evaluation of surgical bypass patency. PMID- 1509067 TI - Diffuse panbronchiolitis: correlation of high-resolution CT and pathologic findings. AB - Diffuse panbronchiolitis (DPB) is characterized by chronic airflow limitation and airway inflammation with bronchiolar lesions. Chest radiographs of patients with DPB usually show small nodular shadows throughout both lungs. The authors investigated the nature and pathogenesis of the radiologic features of DPB by correlating high-resolution computed tomographic (HRCT) findings with histopathologic features. The HRCT images of nine patients with DPB were compared with the observations made with inflated lung specimens. The HRCT findings of DPB included centrilobularly distributed, small rounded areas of attenuation; branched linear areas of attenuation, contiguous with the small rounded areas; dilated airways with thick walls, also common outside secondary pulmonary lobules; and decreased lung attenuation in peripheral areas due to air trapping caused by bronchiolar narrowing in the subpleural zones. The authors believe that HRCT best demonstrates this characteristic location of small rounded areas of attenuation associated with dilated airways. PMID- 1509069 TI - Pulmonary toxoplasmosis in AIDS. AB - The chest radiographs obtained in nine patients with acquired immunodeficiency syndrome (AIDS) and pulmonary toxoplasmosis were reviewed. In three patients, a bilateral, diffuse, fine to medium reticulonodular pattern indistinguishable from that seen in Pneumocystis carinii pneumonia (PCP) was observed. In six patients, however, a bilateral, predominantly coarse, nodular pattern was observed. This type of abnormality is unusual with PCP, and its presence may help in distinguishing between pulmonary infections caused by Toxoplasma gondii and P carinii. Other opportunistic pneumonias occurring in patients with AIDS, including tuberculosis, histoplasmosis, and coccidioidomycosis, might show similar coarse, nodular opacities on chest radiographs and thus may not be differentiated from pulmonary toxoplasmosis. No hilar or mediastinal adenopathy was observed. Two patients had pleural fluid. Radiologists familiar with the chest radiographic appearance of T gondii pneumonia could be first to suggest this unusual complication of AIDS. PMID- 1509068 TI - Pneumothorax after lung biopsy: prevention with transpleural placement of compressed collagen foam plugs. AB - The effectiveness of pleural sealing with a compressed collagen foam plug in preventing the development of pneumothorax was evaluated in a prospective, comparative study of 50 patients undergoing transthoracic needle biopsies. The 4 cm-long plug was deposited through the thin-walled guidance needle at the end of the procedure in a position where it would cross both the visceral and the parietal pleura. The prevalence of postbiopsy pneumothorax was 28% (seven of 25 patients) in the control group and 8% (two of 25 patients) in the plug group. In each study group, two patients with pneumothoraces required chest tubes. Although further experience is necessary, the authors conclude that transpleural collagen foam plug placement may be an effective supplement for transthoracic needle biopsies. PMID- 1509070 TI - Interstitial thermal radiation therapy: five-year experience with head and neck tumors. AB - Sixty-two patients with 24 primary advanced, six persistent, 28 locally recurrent, and four metastatic tumors of the head and neck were treated with combined interstitial low-dose iridium-192 radiation therapy, interstitial 915 MHz microwave hyperthermia (IHT), and external-beam radiation therapy. Diagnoses were squamous cell carcinoma in 56, adenocarcinoma in three, and soft-tissue sarcoma in three lesions. IHT was applied immediately before Ir-192 was placed and after its removal for 45-60 minutes at 41 degrees C-44 degrees C. At 3 months, complete remission had occurred in 39 lesions; partial remission, in 18; and no change or progressive disease, in five. At 12-month follow-up, local control was achieved in 29 of 50 patients; seven other patients had slow ongoing tumor regression with an unclear residual mass at computed tomography or magnetic resonance imaging. Lesion type, tumor volume, total radiation dose, and thermal parameters with "good quality of heating" at high minimum tumor temperature were identified as statistically significant (P less than .05) prognostic factors influencing initial and long-term tumor response. There was no prognostic factor for acute or late thermal damage. PMID- 1509071 TI - Improved radiology film library operations. AB - An interdisciplinary task force at the authors' institution developed a design for a new film library that placed heavy emphasis on service to its customers. The task force established locations and staffing for "satellite" inpatient film libraries organized by clinical specialties. Inpatient films were not permitted to be taken from the radiology department but were available for 24-hour viewing. Film locations were recorded in the radiology information system. Reorganization led to important improvements in film library operations and in the clinical staff's opinion of film library service. Objective measures of performance, such as the fraction of requested films available for conferences, showed significant improvement (P less than .001). Closer working relationships developed between film librarians, radiologists, and their clinical colleagues. Film library personnel were recruited more easily and stayed on the job longer. Several hundred thousand film-tracking transactions per year were recorded. The authors conclude that decentralization of certain film library activities improved many critical aspects of performance. PMID- 1509072 TI - Peripheral MR angiography with variable velocity encoding. Work in progress. AB - An electrocardiographically triggered two-dimensional phase-contrast (PC) magnetic resonance angiographic pulse sequence was developed in which velocity encoding (VENC) was varied throughout an acquisition in response to changes in blood velocity during the cardiac cycle. This was done to better capture signal in the peripheral vasculature, where pulsatile flow degrades images. After reconstruction, a matched filter addition technique was applied to the cardiac phase images to obtain a single high-quality static image. Images were obtained of six healthy volunteers--with and without varying VENC--and contrast-to-noise ratio (C/N) calculations were performed for the added images. Varying VENC significantly improved vascular signal from small and large vessels (P less than .02), but it was most helpful for small vessels, for which the C/N increased by as much as 260% (average increase, 149%). These preliminary findings suggest that variable VENC can enhance the signal from the small and large peripheral blood vessels in cardiac-gated PC acquisitions. PMID- 1509073 TI - Cephalic migration of the bird's nest inferior vena caval filter: report of two cases. AB - The Bird's Nest inferior vena caval filter (Cook, Bloomington, Ind) has been approved for clinical use since 1989. The authors report two cases of cephalic migration of the filter. Both cases of migration occurred in association with a massive thromboembolism after placement of the filter. It appears that a massive thromboembolism can cause this filter to migrate cephalad. The authors suggest that there is potential for nonsurgical management of the migrated filter. PMID- 1509074 TI - Human coronary and peripheral arteries: on-line three-dimensional reconstruction from two-dimensional intravascular US scans. Work in progress. AB - To explore the feasibility of computer-based, on-line three-dimensional reconstruction, timed manual withdrawal (pullback) recordings were obtained with two-dimensional intravascular ultrasound (US) in 42 patients who underwent percutaneous revascularization. Three-dimensional processing was performed with commercial software that stacked serially obtained intravascular US scans and created a new set of data points in four steps: interpolation, segmentation, boundary encoding, and surface rendering. In all 42 patients, satisfactory on line three-dimensional reconstruction was accomplished. In the first three patients, 70-90 seconds was required for three-dimensional processing, and display was limited to the sagittal format. In the next six patients, a sagittal display was rendered in 45-60 seconds, and on-line reconstruction in the cylindrical format was achieved within 30 additional seconds. In the last 33 patients, an unlimited number of sagittal views could be produced in 30-40 seconds, the extra time required for cylindrical display was shortened to 15-20 seconds, and a luminal cast display was added to the on-line menu. PMID- 1509075 TI - Femoropopliteal stent placement: long-term results. AB - Twenty-one patients who underwent percutaneous transluminal angioplasty (PTA) followed by attempted insertion of a self-expandable vascular endoprosthesis for femoropopliteal lesions were prospectively followed up for an average of 17.6 months with angiographic, Doppler ultrasound, and clinical examinations. Stents were placed bilaterally in one patient. Of the 22 lesions, 18 were total occlusions and four, stenoses. Stent placement was successful in 21 of 22 lesions. Nine occlusions occurred: four in the first 30 days and five 1-5 months after PTA. Three patients developed intrastent intimal hyperplasia that necessitated an additional percutaneous procedure. At 12 months, the patency rate without other interventions (the primary patency rate) was 49%. In patients who underwent secondary intervention (fibrinolysis, atherectomy, or PTA), the secondary patency rate was 67%, which fell to 56% after 18 months. At the end of the study, the overall rate of reocclusion was 43%. It is concluded that use of the self-expandable vascular endoprosthesis in the femoropopliteal region likely does not decrease the reocclusion rate after PTA alone. Its use is indicated for treatment of acute closures after femoropopliteal PTA. PMID- 1509076 TI - US-guided percutaneous liver biopsy with plugging of the needle track: a prospective study in 72 high-risk patients. AB - The efficiency, accuracy, and safety of ultrasound-guided liver biopsy with plugging of the needle track were prospectively assessed in 72 patients at high risk for hemorrhage. Seventy-eight biopsy procedures were performed in 72 consecutive patients prospectively classified into four different groups on the basis of coagulation parameters. Sixty-two patients (86%) had severe or moderately severe coagulation disorders. Fifty-four biopsy procedures were performed in 50 patients with diffuse liver disease, and 24 were performed in 24 patients with focal liver lesions. The biopsy track was embolized with gelatin particles and thrombin. Biopsy specimens adequate for histologic diagnosis were obtained in 69 of the 72 patients (96%). In focal lesions, accuracy and sensitivity in the diagnosis of malignancy were 75% and 89%, respectively. Two serious bleeding complications (2.8%) were encountered in two of the patients with major coagulation disorders. Liver biopsy with plugging of the needle track is a practical technique and is a feasible alternative to the transjugular approach. Respective indications for both methods depend on the severity of coagulation disorders and the presence of focal lesions. PMID- 1509077 TI - Evaluation and comparison of automated biopsy devices. Work in progress. AB - The performance of four automated biopsy devices (Bard Biopty, Bard Monopty, Microvasive ASAP 18, Medical Device Technologies Ultra-Cut) was compared when they were used to obtain 96 liver and 96 kidney samples from eight dogs under ultrasound guidance. There was no significant difference in the lengths of the samples obtained with the four devices. The Monopty device yielded a significantly greater mean weight of both kidney (30.8%) and liver (31.6%) samples compared with the other devices. There were no significant differences between the four devices relative to cellular and histologic preservation, crush artifact, and number of renal glomeruli or liver lobules and portal triads. Renal subcapsular hematomas were identified in most instances, and there was no difference between the devices in the amount of renal trauma resulting from their use. There was only one instance of severe injury to the liver. The choice of instrument should remain one of personal preference, since all four devices were satisfactory and none produced significantly greater renal or hepatic injury. PMID- 1509078 TI - MR imaging of patellar tendinitis. AB - To identify magnetic resonance (MR) imaging characteristics of normal patellar tendons and those affected by tendinitis, the authors evaluated MR images obtained in 10 healthy volunteers, in 50 patients who underwent MR imaging for evaluation of knee structures other than the patellar tendon, in 11 patients with patellar tendinitis, and in two athletes with patellar tendon injuries. Normal tendons had uniformly low signal intensity on T1-, T2-, and proton-density weighted images and displayed distinct margins, and the anteroposterior (AP) diameter slightly increased proximally to distally. It was concluded that the AP diameter of a normal tendon, in its proximal portion, should not exceed 7 mm. In patellar tendinitis, the tendon showed increased signal intensity on T1-, T2-, and proton-density-weighted images and increased AP diameter proximally. The margins of affected tendons were indistinct, especially posterior to the thickened segment. In all groups studied, women had thicker proximal tendons than did men. PMID- 1509079 TI - The deep lateral femoral notch: an indirect sign of a torn anterior cruciate ligament. AB - Magnetic resonance (MR) imaging has shown that tears of the anterior cruciate ligament (ACL) are frequently accompanied by meniscal and osseous injuries. Abnormalities of the cartilage overlying the lateral femoral condylopatellar sulcus (notch) also have been noted during arthrotomy of ACL-deficient knees. In this study, the appearance of this sulcus on MR images and the depth of the sulcus on conventional radiographs are compared in patients with normal and torn ACLs to determine whether a deep sulcus is a useful indirect sign of a torn ACL. In 62 patients with clinically and/or arthroscopically confirmed normal ACLs, the mean depth of the lateral femoral sulcus was 0.45 mm (range, 0.0-1.2 mm) compared with 0.89 mm (range, 0.0-5.0 mm) in 41 patients with clinically and/or arthroscopically confirmed ACL tears (significant at the 5% level). No patient with a normal ACL had a sulcus greater than 1.2 mm in depth. A sulcus deeper than 1.5 mm is equivalent to 3 standard deviations above the mean and was a reliable indirect sign of a torn ACL. PMID- 1509080 TI - Ewing sarcoma: MR imaging of chemotherapy-induced changes with histologic correlation. AB - In a study group of 18 consecutive patients with Ewing sarcoma proved by means of biopsy, the signal intensity characteristics of tumor on magnetic resonance (MR) images were assessed before and after chemotherapy. Sixteen patients underwent MR imaging at 1.5 T before chemotherapy; all 18 patients underwent MR imaging at 1.5 T within 10 days after chemotherapy. Standard spin-echo sequences were used with T1 and T2 weighting in all patients. The primary tumor was visualized in all 16 patients who underwent MR imaging before chemotherapy. Histologic correlation, obtained in 14 patients, showed that areas of high T2-weighted signal intensity on MR images obtained after chemotherapy may represent tumor necrosis, cystic hemorrhagic areas, and fibroblastic repair tissue. In 10 patients (71%), microscopic clusters of viable tumor cells were depicted in areas of both low and high signal intensity after treatment. It is concluded that MR imaging is unreliable for exclusion of active disease, although a pattern of change in signal intensity is qualitative evidence of chemotherapeutic effect. PMID- 1509082 TI - Measurement of CT section thickness by using the partial volume effect. AB - A method to calculate section thickness from mean computed tomographic (CT) numbers of two materials in a section (and by varying the ratio of their volume) was developed. A cylindrical water phantom with an acrylic rod at the center was used, and section thickness was measured with two CT scanners. At actual section thicknesses of more than 4 mm, results with this method differed from results of the aluminum ramp method by only about 10%. At section thicknesses of 1-2 mm, however, the difference was about 30%-50%. Measurement with this method was not influenced by filter function and therefore was more accurate than with the aluminum ramp method. PMID- 1509081 TI - MR imaging-guided muscle biopsy for correlation of increased signal intensity with ultrastructural change and delayed-onset muscle soreness after exercise. AB - To determine if there is a correlation between the degree of delayed increase in signal intensity (SI) of muscle after exercise on magnetic resonance (MR) images and the amount of ultrastructural (ULS) injury and delayed-onset muscle soreness (DOMS), MR imaging-guided muscle biopsy was performed to obtain tissue from the legs of nine sedentary subjects 48 hours after downhill running on a treadmill. The degree of soreness was subjectively graded. T1-weighted, spin-density, T2 weighted, and short inversion time inversion-recovery images were obtained before and after biopsy, at 48 and 96 hours after exercise, respectively. The delayed SI increase of muscle on images obtained before biopsy was subjectively graded and measured. The degree of ULS injury was determined with electron micrographs. Serum creatine kinase levels were obtained before and up to 144 hours after exercise at 24-hour intervals. The measured SI, SI grades, and DOMS grades were correlated with the degree of ULS injury. Linear regression analysis revealed poor correlation between the DOMS grades and the degree of ULS injury and good correlation between the SI grade and the degree of ULS injury. PMID- 1509083 TI - Template-guided breast US. AB - The authors modified a standard breast compression plate to allow ultrasound (US) scanning to be performed in the longitudinal and transverse directions with the breast positioned craniocaudally or laterally in a mammographic unit. The technique allows quick mammographic-US correlation of lesions, characterization of lesions as cystic, solid, or indeterminate, and the ability (with coordinates marked on the plate) to proceed directly with aspiration of sonographically indeterminate lesions. PMID- 1509084 TI - Wallstent metallic biliary endoprosthesis: MR imaging characteristics. AB - Image quality and safety of magnetic resonance (MR) imaging were evaluated in vitro and in eight patients with the most commonly employed metallic biliary endoprosthesis. In vitro, the stent produced no tip deflection at 0.6 or 1.5 T. Trace magnetic susceptibility artifact, similar to artifact from a column of air, paralleled the stent. In patients, image degradation was minimal with conventional pulse sequences. Middle-field-strength spin-echo images revealed minimal artifacts indistinguishable from those produced by pneumobilia. PMID- 1509085 TI - Hickman pseudonodule. PMID- 1509086 TI - Quantitative comparison of academic and private practice radiologists. PMID- 1509087 TI - Acronyms in bone densitometry. PMID- 1509088 TI - Nurses complain--Dr. terminated: RICO suit v. hosp. PMID- 1509089 TI - Court upholds nurse's refusal to float. Case in point: Winkleman v. Beloit Memorial Hosp. (483 N.W. 2d 211--WI [1992]). PMID- 1509090 TI - Legal case briefs for nurses. ID: refusal to meet supervisor without witness: termination for misconduct; GA: nurse sued for negligent i.v. site selection: standard of care issue. PMID- 1509091 TI - Mystery nurse reports child's sexually transmitted disease in error. Case in point: Perez v. Bay Area Hospital (829 P. Rptr. 2d 700--OR [1992]). PMID- 1509092 TI - Groundworks for an evolutionary biochemistry: the iron-sulphur world. PMID- 1509093 TI - Electrostatic fields in antibodies and antibody/antigen complexes. PMID- 1509094 TI - Basement membranes in neoplasia. PMID- 1509095 TI - [Nationalism, hatred of foreigners and antisemitism. Psychoanalytic considerations]. AB - Widespread social crisis phenomena such as unemployment, shortage of housing or lack of prospects are not sufficient to explain aggressive nationalism and the revival of xenophobia in present-day Germany. While from a psychoanalytic viewpoint xenophobia and anti-Semitism have been extensively examined, the same can by no means be said of the phantasm of the "nation". With reference to a case study, the author demonstrates that the adoption of nationalist ideologies (which in Germany specifically are very much bound up with the traditional notion of the nation as a biological organism) can serve both to prevent the outbreak of neurosis at the individual level and to effect what Freud called the "spurious" healing of existing neuroses. Psychologically speaking, the phantasm of the "nation" provides scope for the realization of the desire for pre-ambivalent fusion with an object that has rid itself of everything heterogeneous, alien and autonomous. PMID- 1509096 TI - [Hatred of foreigners and purity--current aspects of an illusion. Social psychological and psychoanalytic considerations]. AB - This study draws upon both Carlo Ginzburg's procedures for establishing and preserving (historical) evidence and Claude Levi-Strauss' structuralist approach with its analysis of "primitive" mythologies to demonstrate that binary coding of the social domain is an all-pervasive structural principle. Heim's intention in this is to show that (present-day) xenophobia and racism are the products of a phantasm centering around the division of the world into pure and impure. The author brings into alignment collective fantasies about the homogeneity of the "body politic" with a form of primary narcissism which, if it is to preserve the illusion of original purity, is forced to externalize instinctual urges experienced as heterogeneous and unpleasurable and project them onto "foreigners" and things foreign. PMID- 1509097 TI - [Native and alien. On ethnic identity]. AB - Freud's theory of the antagonism between family and culture provides the point of departure for this study, which sets out to rehabilitate the concepts "ethnic" and "ethnic identity". The family represents the locus of established tradition and familiar ritual and seeks to make each new generation identify with "us and ours". Culture, by contrast, is dependent on contact and confrontation with things alien and foreign. Between these extremes and the potential dangers specific to each of them, ethnicity--which is neither biological nor cultural- represents a mediating factor. In adolescence, a phase of dis- and re orientation, the individual needs to draw upon his ethnic identity to reconcile the disturbing contradiction between familial and cultural claims, between the native and the alien. PMID- 1509098 TI - ["Proud of violence". Psychoanalytic remarks on adolescence and right extremism]. AB - Young people with extremist right-wing leanings who join together to form gangs frequently come from a social background which has had a traumatic influence on their biographies from an early stage. The right-wing radical group functions as a substitute for caring parents and other figures that these youngsters can look up to. Within these constellations they then act out the violence that they themselves have been the victims of. The author points out that, both on an individual and social plane, these young people stand for facets of our own selves that we have severed off or negated and conflicts which we have yet to come to terms with. PMID- 1509099 TI - [Editorial introduction of Ernst Simmel's "Self preservation and the death instinct"]. PMID- 1509100 TI - [Self preservation and the death instinct. 1944]. PMID- 1509101 TI - MR imaging of late radiation brain injury. AB - One hundred and four patients treated with radiotherapy for intracranial tumors and their related conditions were reviewed to evaluate the usefulness of magnetic resonance (MR) imaging in demonstrating increased signal intensity areas on T2 weighted images that were considered to be late adverse effects of irradiation of the brain. High signal intensity areas of the white matter were divided into five patterns according to their size and extension. Severity was found to increase with age and irradiation doses of more than 50 Gy. In patients with irradiation doses of more than 60 Gy, the severity of increased with shorter interval after radiotherapy than in those given low irradiation doses. Clinical findings such as mental deterioration, motor abnormality, and visual defect were observed in 12 patients. These findings were closely correlated with the severity of the MR pattern. In most patients, high signal intensity areas were stable or progressive during the course of follow-up. However, these areas were regressive in three patients. Imaging with Gd-DTPA was performed in 36 patients, six of whom showed enhancement. Pathological findings on enhancement included astrocyte proliferation and coalescing vacuoles in neural tissue. MR imaging is an excellent method with which to monitor the adverse effects of radiotherapy of the brain. PMID- 1509102 TI - MR Gd-DTPA enhancement of radiation brain injury. AB - MR examinations of 104 patients who had undergone radiotherapy to the brain were reviewed. Thirty-six patients received Gd-DTPA enhanced study during the course of MR evaluation and six of the patients showed enhancing radiation necrosis. Histopathological confirmations were obtained in three patients. Gd-DTPA enhancing radiation lesions were multiple and patchy in three patients, multiple and patchy with cyst formation in two and ring shaped in one. In terms of their distribution, enhancing lesions in four patients were seen only in the white matter within the irradiated field and these patients had undergone radiotherapy within five years. The interval after radiotherapy was more than eight years in two patients and their enhanced lesions were observed in both the white and gray matter. Histopathological findings of Gd-DTPA enhancing radiation necrosis were gliosis and coalescing vacuoles of the neural tissue. None of these enhanced radiation lesions showed significant mass effects. Patterns of the enhancement were not specific. It was considered to be difficult to differentiate tumor recurrence from radiation necrosis with conventional Gd-DTPA enhanced MR examinations. In one patient, delayed MR images after Gd-DTPA administration showed increases in the size and number of radiation enhanced lesions. Dynamic and delayed MR study might add more information to conventional imaging after Gd DTPA. Further studies are necessary to differentiate radiation lesions from tumor recurrences. PMID- 1509103 TI - MR imaging in uterine cervical cancer after radiotherapy. AB - The usefulness of MR imaging (MRI) in uterine cervical cancer after radiotherapy was evaluated in 18 patients. MRI was performed before and within one month after radiotherapy. In eight patients the uterus assumed a nearly normal appearance with resolution of the tumor on MRI. In another eight patients the tumors resolved, but an area of high signal intensity remained at the cervix. In these patients the tumors were well controlled at clinical examinations and during the mean follow-up period of 15-18 months. Therefore a persistent area of high signal intensity alone at the cervix on MRI is not itself indicative of residual tumor. An area of high signal intensity and a residual cervical mass persisted in two cases, and they were histologically proven to be due to residual tumor. Both patients died of recurrent disease at seven and 11 months after their radiotherapy. We conclude that MRI is useful for evaluating patients with cervical cancer at the completion of radiotherapy, and that MRI complements conventional clinical examinations. PMID- 1509104 TI - Intraluminal irradiation for T2M0 esophageal cancer: effect of patient selection on prognosis. AB - The contribution of intraluminal irradiation to the prognosis of T2M0 esophageal cancer was examined with reference to patient selection. To determine the effect of patient selection, we used esophagrams to assess the potential difficulty of inserting a tube for intraluminal irradiation in 39 patients who were treated with external irradiation prior to 1982. Twenty-two patients were assessed as likely to have been able to undergo intraluminal irradiation (group 1) while 17 were assessed as unlikely to have been able to undergo the procedure (group 2). Of 36 patients treated after 1983, 19 patients were treated with a combination of intraluminal irradiation and external beam therapy (group 3) and 17 by external irradiation alone (group 4). The median survival times of groups 1, 2, 3, and 4 were 10.8, 6.4, 12.0, and 8.5 months, respectively. The prognosis of patients treated with combination therapy (group 3) was superior to that of those treated before 1982 (groups 1 + 2). However, there was no improvement in the prognosis of T2M0 esophageal cancer treated by radiotherapy after the introduction of intraluminal irradiation, and the difference between the survival curves of patients treated by combination therapy (group 3) and with a wide esophageal lumen (group 1) was not significant. Our study thus showed that the selection of patients according to the insertability of the intraluminal therapy tube affected the prognosis. PMID- 1509105 TI - Digital angiography using hand-operated table movement for vascular disease of the pelvis and lower extremities. AB - We developed a new technique using hand-operated table movement during digital angiography (DA) for the study of vascular disease of the pelvis and lower extremities. Digital video memory (DVM) is used in this technique to digitize, record, and display fluorographic images without subtraction in real time. This allows free table movement and the imaging of a large area with a single injection of contrast medium. Forty-five examinations for vascular disease of the pelvis and lower extremities were performed by this DA technique. Good images of an extensive area from the lower abdomen to the lower leg were obtained in a single study. PMID- 1509106 TI - Asymmetrical FDG-PET and MRI findings of striatonigral system in multiple system atrophy with hemiparkinsonism. AB - The asymmetry of the local cerebral metabolic rate for glucose (lCMRglc) and magnetic resonance (MR) imaging was studied in five patients with multiple system atrophy (MSA) presenting hemiparkinsonism. lCMRglc was measured with 18F-2-fluoro 2-deoxy-D-glucose and positron emission tomography (PET) in these patients and five normal control subjects. MR images were obtained in five patients and 11 control subjects. In all patients, T2-weighted MR images showed hypointense areas in the posterior lateral putamen. They were bigger or lower in intensity on the contralateral side than on the ipsilateral side. Significant glucose hypometabolism was found in the posterior putamen on the contralateral side to hemiparkinsonism. A significant decrease in size was found in the contralateral putamen, caudate nucleus, and pars compacta of the substantia nigra. However, no significant correlation was seen between PET and MRI data. In the control subjects, no apparent asymmetry was observed. PET and MR imaging demonstrated the characteristic asymmetry corresponding to the pathological findings reported in MSA. PMID- 1509108 TI - 11th annual meeting of the European Society for Therapeutic Radiology and Oncology. Malmo, Sweden, 1-4 September 1992. Abstract. PMID- 1509107 TI - Carbon-13 chemical shift imaging of [1-13C] glucose under metabolism in the rat head in vivo. AB - Carbon-13 chemical shift images (metabolic maps) of [1-13C] glucose in the heads of rats were obtained and compared with proton images of the same rats in terms of signal allocation. Wistar rats were kept awake or anesthetized. [1-13C] glucose was injected intravenously in a dose of 1 g per kg of body weight. The head of the Wistar rat was placed on or into circular coils. Carbon-13 images were obtained using a 7.05 Tesla system. A simple spin echo sequence was used with a chemical shift selective (CHESS) pulse. The frequency band width was set to cover the spectral breadth of the carbon-13 signal of [1-13C] glucose. The slice thickness of the image was 4 mm or 6 mm, and the field of view (FOV) was 60 mm x 60 mm, with a matrix size of 64 x 64. The total acquisition time was 36 minutes. Strong signals were observed from the scalp muscles and tissues outside the brain, but signal strength from the brain itself was minimal. This was presumably due to the metabolism of [1-13C] glucose in the brain. Little difference was recognized between [1-13C] glucose images of the heads of rats with and without anesthesia. Chemical shift imaging of carbon-13 could be useful methods for the in vivo study of physiochemical structures and metabolic pathways of living organs. PMID- 1509109 TI - On small samples and good ideas. PMID- 1509110 TI - Psychosocial outcome six months after heart transplant surgery: a preliminary report. AB - With improvement in survival of patients treated with heart transplant, evaluation of recovery with respect to psychosocial function has become an important issue. In this study, psychosocial functioning of 44 heart transplant recipients pretransplant was compared to their functioning 6 months posttransplant. Before transplantation, patients experienced considerable psychosocial distress attributable to illness. At 6 months after transplantation, the majority of patients showed significant improvement in emotional, domestic, sexual, social, and vocational functioning. However, 25% of patients showed deterioration in psychosocial adjustment and 11% showed an increase in mood disturbance. Further effort is indicated to improve psychosocial outcome of heart transplantation. PMID- 1509111 TI - Holistic health patterning in multiple sclerosis. AB - Multidimensional health patterning of three groups of persons with multiple sclerosis (MS) was examined. Changing patterns over a 5-year period for each group also were examined. Serial self-assessments of the subjects' prevalence of MS-related symptoms (motor, brainstem, sensory, elimination, mental-emotional) and level of ADL functioning (fine and gross motor activities, sensory/communication, socializing/recreation, intimacy) were obtained by mail. The number of subjects grouped by years since diagnosis was: 69 (0-5), 49 (greater than 5-10), and 93 (greater than 10). Study findings indicated significantly higher levels of functioning in areas of fine and gross motor activities and intimacy among the more recently diagnosed group but no difference among the groups for sensory/communication, recreation/socializing, and symptoms. Significant increases in motor and brainstem symptoms and decline in fine and gross motor activities and intimacy occurred over the 5-year period particularly for the 0 to 5 year postdiagnosis group. Knowledge of symptom and ADL patterning is essential for nurses and other health care providers in anticipating the concerns and needed services of persons with MS and their families. PMID- 1509112 TI - Interactions of parents and nurses with high-risk preterm infants. AB - The interactions of preterm infants with parents were compared with their interactions with nurses. Twenty-nine high-risk preterm infants who were a part of a larger longitudinal study of behavioral development were observed once weekly from 7 p.m. to 11 p.m. A single observation for each infant that contained a minimum of 2 min of parental care and 2 min of nursing care was selected for analysis. Results showed that nurses and parents provided different types of stimulation with nurses more likely to engage in procedural care and parents more likely to hold, talk to, move, and touch the infants affectionately. Infants showed more sleep-wake transition, large body movements, and jitters when with nurses and more active sleep and more smiles when with parents. Similar differences were found when parents and nurses were just holding or touching the infants, but no differences in infant responses were seen during feeding or changing. Thus, the different infant behavioral responses appeared to result primarily from the different stimulation provided by parents and nurses. Implications of these findings for research and clinical practice are discussed. PMID- 1509113 TI - Adolescent stress and coping: a longitudinal study. AB - The purpose of this longitudinal panel study was to investigate developmental and gender influences on stress and coping in adolescents attending a suburban high school in Tennessee. Data were collected from the same 167 subjects during the freshman year and again during the senior year. Life events stress was measured through the Adolescent Life Change Event Scale (ALCES) and ways of coping were categorized from data gathered from an open-ended questionnaire. Girls reported more life events stress at both testings than boys. Life events stress was greater at senior testing for both girls and boys, but girls' scores increased more. The "gender intensification" phenomenon may account for the greater disparity in types of stress reported by boys and girls as seniors. Girls generally reported more life events associated with interpersonal and family relationships. Both girls and boys reported coping with stress mostly through active distraction techniques such as exercise. However, girls' use of active distraction decreased over time, while passive distraction increased. Self destructive and aggressive coping behaviors increased for boys. There were no relationships between amounts or types of life events stress and ways of coping for subjects at either time. PMID- 1509114 TI - Correlates of battering during pregnancy. AB - Battering during pregnancy affects the health of both pregnant women and their unborn children. The purpose of this retrospective study of 488 primarily Medicaid-eligible postpartum women was to identify the constellation of factors associated with violence. The prevalence of battering during pregnancy was 7%, similar to that found in other studies. Significant correlates of battering included anxiety, depression, housing problems, inadequate prenatal care, and drug and alcohol use. Woman battering by a partner during pregnancy was associated with a greater severity of this constellation of patterns than those experiencing abuse before pregnancy only, or those experiencing physical attack by someone other than their partner. These factors are important to recognize in nursing assessment of pregnant women. PMID- 1509115 TI - Psychometric examination of instruments using aggregated data. AB - The techniques used to examine the psychometric properties of instruments that measure concepts where individual responses are aggregated to form an index describing a group level phenomenon are reviewed. This examination includes assessing the content validity of items to determine how well they measure group level concepts as well as analyzing reliability and validity at the aggregated rather than individual level. Additional techniques to test for within and between group variability are presented. The latter approaches are useful in determining the consistency and adequacy of individual responses at the group level. PMID- 1509116 TI - Risk assessments and chronobiology. PMID- 1509117 TI - Alterations of the circadian melatonin rhythm by the electromagnetic spectrum: a study in environmental toxicology. AB - The nightly production and secretion of melatonin by the pineal gland, an endocrine organ near the anatomical center of the brain, provides important time of-day and time-of-year information to the remainder of the body. In mammals, the circadian rhythm of melatonin (low levels during the day and high levels at night) is synchronized by the prevailing light:dark environment with the retinas of the eyes doing the photoreception required for the induction of this rhythm. The advent of artificial light sources has allowed animals or humans to be exposed to light at unusual times, i.e., during the night. Light falling on the retinas at night leads to a rapid depression in the production and secretion of melatonin by the pineal gland. The magnitude of the drop in circulating melatonin due to light exposure at night is related to the brightness (intensity) as well as the wavelength (color) of light to which humans are exposed. The lowered melatonin values following unusual light exposure at night provide erroneous information to a number of organs that respond to the melatonin message since the signal implies it is day when, in fact, it is still night. Besides visible light, certain ultraviolet wavelengths as well as extremely low frequency electric and magnetic fields may also disturb the melatonin rhythm. These nonvisible wavelengths may influence the circadian melatonin rhythm by mechanisms similar to those by which light causes disturbances of melatonin production and release. PMID- 1509118 TI - Hepatotoxicity and carcinogenicity in female Sprague-Dawley rats treated with 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD): a pathology working group reevaluation. AB - Risk assessment for 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) has been based in part on the incidences of liver neoplasms in female Sprague-Dawley (SD) rats reported in a 2-year study conducted by Dow Chemical Corporation and published in 1978. In the years subsequent to the Dow report, the criteria for the diagnosis of proliferative hepatocellular lesions in the rat have been refined based upon ongoing study of these lesions. Because of this, PATHCO, Inc., was requested to conduct an independent review of the liver slides from the Dow TCDD study in order to assess how the current terminology might impact on interpretation of proliferative liver lesions in rats compared to the terminology used in the past. In March 1990, a pathology working group (PWG) was convened to review proliferative lesions in the livers of the female rats. The results of the PWG's evaluation of the microslides indicated a trend in tumor incidence similar to that published in 1978 but with a lower incidence of tumors in the middle and high dose females. Based on the morphologic findings, including the fact that the tumors were predominantly benign and usually associated with lesions of hepatic toxicity, the PWG considered this study to demonstrate a weak oncogenic effect of TCDD in the livers of female SD rats. As a result of its review, the PWG noted that in order to establish a relationship between the toxic hepatitis and the hepatocellular neoplasms, an independent review and grading of the toxic lesions in all female rats would be required.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1509119 TI - A review and biological risk assessment of sodium saccharin. AB - Dietary sodium saccharin is associated with bladder tumors when fed at high levels to the male rat. Under these conditions urinary pH, sodium concentration, and volume are elevated and proliferative changes are present in the urothelium. Extensive epidemiological studies have shown that saccharin does not increase the risk of bladder cancer in humans and laboratory investigations have shown that sodium saccharin is not mutagenic and does not bind to DNA. Recent research indicates that the urothelium in male rats is damaged under conditions of high urinary pH and sodium levels by a mechanism that involves alpha 2u-globulin and possibly silicate crystalluria. These studies and their implications for human health risk are reviewed. PMID- 1509120 TI - Cancer risk--does anyone really care? AB - Congress has enacted numerous laws in an attempt to protect people from carcinogens. But neither regulators nor oncologists can hope to accomplish this protection via studies in epidemiology. Nor can they hope to accomplish this using unverified models in carcinogenesis bioassays. The only viable hope is to test and utilize models of carcinogenicity that will tell us what we really need to know; i.e., does this substance pose a reasonable risk of carcinogenesis in man? And if so, what is a quantitative estimate of that risk? There is a substantial number of known human carcinogens. Yet, the most elaborate cancer testing facility in the world continues to operate without the benefit of validating its results using positive controls (known human carcinogens). Without such controls to gauge the potency of the response in the test animal, Congress can pass 10,000 more laws and still the public will remain unprotected. PMID- 1509121 TI - Alternative acute inhalation toxicity testing by determination of the concentration-time-mortality relationship: experimental comparison with standard LC50 testing. AB - A new design for acute inhalation toxicity testing was evaluated and compared with results obtained according to OECD guideline 403. The new design consists of a range-finding test, which is compatible with a conventional limit test, and can be followed by determination of a concentration-time-mortality relationship, enabling calculation of LC50 (50% mortality exposure concentration) values. By exposing pairs of rats for different periods of time to about four different test concentrations in a nose-only exposure unit, LT50 (50% mortality exposure time) values were obtained for five pairs of animals per concentration. The mortality data of the approximate 20 time-concentration combinations were used to calculate the probit relationship. Estimated mortality responses from these probit relations were compared with mortality figures obtained by exposing groups of five male rats and five female rats whole-body according to conventional toxicity testing. In general, there was good correspondence between the estimated and the observed mortality response. In our hands, the determination of the concentration time-mortality relationship takes about the same number of animals (40-50) as the conventional LC50 procedure according to the OECD guideline 403. However, the new method has several additional advantages such as: (A) LC50 values are obtained over a 10-fold range in time, with the potential of decreasing the number of animals used when regulations require acute toxicity data for different periods of exposure. (B) The obtained relationship contains considerably more valuable information for risk assessment than the LC50 value.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1509122 TI - Scientific and practical considerations for the development of occupational exposure limits (OELs) for chemical substances. AB - Occupational exposure limits (OELs) serve occupational health professionals as benchmarks for a healthy work environment. OELs are generally developed by manufacturers for substances which are not subject to governmental regulation or which have not been evaluated by consensus organizations such as the American Conference of Governmental Industrial Hygienists. This review is intended to serve as a practical guide to the standard-setting process. The discussion encompasses the evaluation of data, the different methods used for calculating limits, and the application of these limits to the workplace. The need for additional research to enhance the reliability of current methods is also discussed. PMID- 1509123 TI - [The normal topographic and CT-tomographic anatomy of the ostiomeatal complex]. AB - Recent advances in the pathophysiology of the nasal cavity and paranasal sinuses and the development of endoscopic equipment and techniques have led to a new "functional" surgical management of chronic or recurrent sinusal conditions. The ostiomeatal complex is a narrow and intricate passage way providing aeration and mucus clearance from anterior ethmoid sinus, maxillary sinus and frontal sinus. CT, allowing the detailed demonstration of normal and abnormal patterns of the ostiomeatal complex, permits accurate preoperative planning, which has reduced the number of surgical complications. Ostiomeatal complex anatomy and the corresponding CT features are analyzed, as seen in 85 patients with or without rhinosinusal inflammatory lesions. The CT technique with coronal and axial scans and electronic parasagittal reconstructions, is also reported. Finally, the images obtained on different CT planes are compared, as proposed by other authors. PMID- 1509124 TI - [Interventional radiology in the treatment of the complications from interventions on the lower urinary excretory tract]. AB - Ureteral diversions may be complicated by strictures, hydronephrosis, pyelonephritis, lithiasis, fistulas, etc. In the last 10 years, 103 patients with 133 urological postoperative complications underwent percutaneous treatment. Most of the patients had been treated by percutaneous antegrade drainage; afterwards, stricture dilatation, ureteral stenting and stone extraction were performed. In one case a Strecker metallic stent was employed. We have successfully treated 101 of 133 complications (75.9%), with only 27 failures (20.3%). Five cases (3.8%) of lithiasis did not require percutaneous treatment. The good results obtained, the absence of major complications, the low cost and the little discomfort for the patients confirm the leading role of percutaneous treatment in complicated ureteral diversions. PMID- 1509125 TI - [A comparison between quantitative computed tomography and dual-energy densitometry in the study of patients at risk for postmenopausal osteoporosis]. AB - A comparison was made of the densitometric values of the lumbar vertebrae obtained using quantitative Computed Tomography, and those measured with dual energy X-ray absorptiometry. A selected group of patients at increased risk of developing postmenopausal osteoporosis was chosen: women who had undergone bilateral oophorectomy in child-bearing years. The densitometric data recorded revealed a considerable decrease in bone mass, in particular in the cancellous portion of the vertebrae (a 17% change in the quantitative Computed Tomography value and a 13% decrease in that of dual energy X-ray absorptiometry a one year after oophorectomy). Although quantitative Computed Tomography and dual energy X ray absorptiometry demonstrated a similar trend in bone mass reduction, given the marked and unexplained variability of both absolute values and percent variations, it was impossible to establish a clinically useful mathematical correlation between the two sets of data. Quantitative Computed Tomography is the densitometric procedure of choice to study metabolic bone disorders that involve mainly tha cancellous portion, such as postmenopausal osteoporosis. Nevertheless, given its accuracy, short execution time, lower radiation dose required, as well as good sensitivity in the measurement of bone mass variations, it would seem that dual energy X-ray absorptiometry could also find a place in clinical studies on postmenopausal osteoporosis. PMID- 1509126 TI - [The results of definitive transcutaneous radiotherapy in the treatment of oropharyngeal neoplasms]. AB - From January 1976 to December 1986, 199 patients with oropharyngeal cancer were submitted to definitive radiotherapy. Survival and local control were analyzed and related to different parameters--i.e, T and N categories, histopathologic grading, tumor location, patients age, and radiation dose. Fifty-six per cent of patients (111/199) died from neoplastic disease within 5 years. Local progression, recurrence or metastases were observed in 149 cases (75%). Ninety three per cent of first failures (138/149) were related to residual disease or to locoregional relapse while distant metastases occurred in 14 patients only. The majority of locoregional failures (94%) appeared within 2 years, with a mean disease-free interval of 8 months. Tumor recurrence in the primary location was observed to be the first cause of failure in 78% of relapsed patients; moreover, it was the sole cause of failure in half of the unfavorable events. On the contrary, nodal relapse appeared in 38% of treatment failures and in 12% only it was the sole cause of failure. Overall and disease-free survival were observed to depend mainly on T and N categories, while histopathologic grading was seen to affect only early response rate. No significant differences were observed depending on tumor site and patients age. Local control rates depended on total radiation dose, but the difference between low dose (NSD less than 1700) and high dose (NSD greater than 1700) was significant only for T1 and T2 patients. PMID- 1509127 TI - [Radiotherapy in the treatment of Merkel cell tumors]. AB - Merkel cell carcinomas are very rare (80 cases up to 1986) and very malignant; they have been known for 20 years only as "trabecular carcinomas". They do not rise from neural crests, and therefore are not apudomas, but from a staminal cell of the skin with neuroendocrine evolution. Merkel cell carcinomas must be distinguished from undifferentiated carcinomas of the skin, lymphomas, and oat cell carcinomas. Eight patients (46 to 86 years old) are presented, 4 males and 4 females, with 1 gluteal (the younger female patient), 3 head and 4 limb localizations of Merkel cell carcinoma. Radiotherapy was carried out after surgery in 7 patients and after biopsy in 1; local recurrences were already present in 3 cases, and lymph node metastases in 5; tumor doses were 36-65 Gy, administered with different techniques, i.e. roentgen therapy, telecobalt therapy, 192Ir curietherapy. Chemotherapy was used in 2 metastatic patients only. Four patients are alive and free of disease and 4 are dead; 3 of the living patients have been followed 3-26 months. The high risk of radiation damage (1 necrosis, 2 giant edemas, 1 severe fibrosis) recommends that large fields and high single and/or total radiation doses be avoided. In conclusion, surgery is diagnostic but not curative on account of the high risk of recurrence; radiotherapy is important because Merkel cell carcinomas are very radiosensitive. Due to easy lymphatic spread of this type of cancer, radiotherapy must include the regional lymph nodes (dose: 40-50 Gy). The role of chemotherapy is still to be assessed but many antiblastic drugs are effective. PMID- 1509128 TI - [Ambulatory monitoring of left ventricular function with a radionuclide detector system]. AB - The recent development of new radionuclide detectors allows noninvasive outpatient monitoring of left ventricular function. This study was aimed at describing a new radionuclide technique useful to monitor cardiac function and at evaluating its potential clinical applications. We studied 14 normal subjects, 30 patients with coronary artery disease and 25 patients with dilated cardiomyopathy. Left ventricular function was continuously monitored in control conditions at rest, during daily physical activity of different intensity (walking on a level surface and climbing stairs), and during bicycle exercise. Left ventricular ejection fraction (EF) variability during recording in control conditions at rest was 0.2 +/- 1.8%. A significant relationship between outpatient EF at rest and conventional equilibrium radionuclide angiography was observed (r = 0.97, n = 69, p less than 0.001). In normal subjects both daily physical activity and exercise stress test induced an increase in heart rate and EF. In patients with coronary artery disease and in patients with dilated cardiomyopathy a heterogeneous EF response was observed during physical activity and exercise stress test. Our results demonstrate that this technique can be used for the ambulatory monitoring of left ventricular function in both normal subjects and patients with different types of cardiomyopathies. PMID- 1509129 TI - [A rare case of neurilemmoma studied by echotomography]. PMID- 1509130 TI - [A radiation-induced meningioma of the middle cranial fossa invading the orbit and temporal fossa in a subject with a previous retinoblastoma]. PMID- 1509131 TI - [Magnetic resonance with spin-echo and gradient-echo technics and magnetic resonance angiography in the study of a case of carotid paraganglioma]. PMID- 1509132 TI - [Acute rhabdomyolysis due to heroin. A case report]. PMID- 1509133 TI - [Magnetic resonance in the diagnosis and follow-up of soft-tissue sarcomas]. AB - The authors analyze the advantages of MR imaging in the detection, staging and follow-up of malignant soft-tissue sarcomas. The role of MR imaging is retrospectively evaluated in 34 patients (16 men and 18 women) ranging in age from 3 to 82 years (mean: 38); 19 of them had a primary neoplasm, while the extant 15 patients were examined after surgery, and residual or recurrent tumors were present. Ten examinations were performed on an 0.5 T imager (CGR Magniscan 5000), and 27 were obtained with a 1.5 T system (Magnetom 42 SP Siemens). In all cases T1 and T2 sequences were acquired; in 3 patients T1-weighted sequences were performed after Gd-DTPA administration. In the 19 patients with primary tumors pathologic specimens were obtained. The value of MR imaging in the evaluation and characterization of soft-tissue sarcomas and its capabilities in detecting neurovascular encasement and bone involvement are discussed. Post-Gd-DTPA scans may help in the differentiation of necrotic areas from active tumors. MR diagnostic criteria of malignancy, including tissue heterogeneity and irregular margins, were not fulfilled in 3 of the studied cases. PMID- 1509134 TI - [The echographic picture of the recent rupture of Baker's cyst. A case report]. PMID- 1509135 TI - [The regression after chemotherapy of the breast metastases from a malignant melanoma. The mammographic analysis of a case]. PMID- 1509136 TI - [A cystic lymphangioma of the retroperitoneum. A case report]. PMID- 1509137 TI - [An intramural hematoma of the duodenum: the possibilities for radiologic diagnosis. 3 cases]. PMID- 1509139 TI - [An accessory musculus soleus (symptomatic and asymptomatic). The CT findings]. AB - The authors have reviewed 90 CT exams of the foot to identify the presence of the accessory soleus muscle, an anatomic variant corresponding to the finding of a medial backtibial tumefaction, often aching, especially of the Achilles-calcaneal plantar system. In these cases, US is generally required to demonstrate the alteration, which was an occasional finding in the past, and to exclude the presence of inflammatory or expansile processes of the soft tissues. The accessory soleus is characterized by the presence of accessory muscle fibers, which, in variable number, caudally make for the medial aspect of the calcaneus from the antinode of the soleus muscle. The anatomic variant is much better evidenced by CT, more frequently employed than MR imaging, thanks to its easier approach. As a matter of fact, both methods are capable of defining the relationships with the adjacent tendinous-vascular-nervous structures, involved by mechanical friction in the event of muscle hypertrophy due to overload. Indeed, the review of CT examinations has pointed out a relative relationship between volumetric changes in the soleus and nonphysiological functional demands, giving further evidence of its specific role in the efficiency of the Achilles calcaneal-plantar system. Therefore, the report in asymptomatic cases is an important prognostic factor which allows the correct clinical picture of subsequent painful symptoms. PMID- 1509138 TI - [The imaging diagnosis of retained sponges in the abdomen. Apropos 2 cases]. PMID- 1509140 TI - [Microcalcifications in the diagnosis and follow-up after the primary chemotherapy of breast neoplasms]. AB - Since 1998, at the National Cancer Institute (Milan, Italy), a study has been carried on relative to primary chemotherapy for locally advanced breast cancers (greater than 3 cm diameter). Aim of the study is to obtain tumor reduction and thus allow a conservative treatment to be performed. The measures of the two greatest diameters of the tumor by means of mammography, at diagnosis and after chemotherapy, are important parameters for treatment planning. Among the 213 patients who completed the whole diagnostic-therapeutic procedures by December 1990, the authors chose 94 cases (44%) presenting breast cancers with microcalcifications and reviewed the relative mammograms. The review was aimed at analyzing morphology, number and extent of the microcalcifications and at assessing their value as reliable parameters of cancer response to primary chemotherapy. In their experience, the authors found that increased visibility of the microcalcifications after chemotherapy is often due to a reduction in both edema and lesion opacity. On the contrary, fewer microcalcifications may be correlated with incisional diagnostic biopsies. In conclusion, if microcalcifications are a useful parameter for diagnosis, they alone are less important when evaluating response to primary chemotherapy, since they probably represent a permanent sign of the extent of the primary lesion. All follow-up mammograms of the patients who underwent conservative surgery were also reviewed: no residual microcalcifications or other suspicious abnormalities were observed. PMID- 1509141 TI - [Mammography and echography in male breast pathology]. AB - From January 1988 through December 1991, 81 men were examined for breast enlargement or mass in our Institute, by means of clinical examination, mammography, and US. The patients' age ranged 15-71 years (mean: 52 years). Of 81 studied patients, 71 had gynecomastia, 8 had adipomastia, 1 had an infiltrating ductal carcinoma, 1 an angiofibrolipoma and 1 a simple cyst. Both the carcinoma and the cyst were associated with gynecomastia. Three mammographic patterns of gynecomastia were observed: a glandular pattern in 42 cases (32 bilateral and 10 monolateral), a dendritic pattern in 12 (8 bilateral and 4 monolateral), and a nodular pattern in 15 (9 bilateral and 6 monolateral). On US, gynecomastia appeared diffuse in 54 patients and focal in 15. The infiltrating ductal carcinoma was clinically evident; no asymptomatic cancers were detected. Surgical biopsy was performed in 40 cases. A good correlation was observed between mammographic and US signs. The combined use of the two modalities can improve diagnostic accuracy. Biopsy must be performed in all questionable cases. PMID- 1509143 TI - [The computed tomographic diagnosis of malignant pleural mesothelioma. A multicenter study]. AB - CT features are described and accuracy of the method is discussed in the diagnosis of malignant pleural mesothelioma. Ninety-eight patients suffering from pleural disease mimicking mesothelioma were examined by means of III-generation CT scanners; according to the final diagnosis, 37 patients suffered from malignant pleural mesothelioma, 27 from other malignant pleural diseases and 34 from various benign diseases. In all patients a series of CT signs was evaluated: pleural thickening patterns, lesion spread and possible associated characters. In the diagnosis of mesothelioma CT showed 72.5% sensitivity, 63.8% specificity, 68.3% diagnostic accuracy, 68.5% positive predictive value and 68.2% negative predictive value. Some significant CT patterns in distinguishing malignant from benign pleural disease were identified, while the characterization of malignant disease (mesothelioma versus other neoplastic conditions) proved to be unreliable. PMID- 1509142 TI - [Magnetic resonance in the diagnosis of thyroid diseases]. AB - Previous clinical experience in the study of the soft tissues of the neck region has pointed out the accuracy of MRI in terms of high definition and contrast resolution. Seventy-seven patients with thyroid diseases were examined to define the possible role of MRI in the diagnosis of these conditions. In the patients affected with thyroiditis, MR findings were not specific, showing increased glandular volume and signal inhomogeneity. MR examinations of struma allowed an accurate evaluation of glandular size; furthermore, more information was obtained than with other imaging modalities in the cases with mediastinal involvement. On T2-weighted images, adenomas were always hyperintense, whereas variable signal intensity was seen on T1-weighted scans, with the exception of Hurthle cell adenomas, which were hyperintense on both T1- and T2-weighted sequences. MRI proved to be reliable in the depiction of tumor spread at both glandular and extraglandular levels. The distinction between scar fibrosis and relapse was also possible, in the cases undergoing postoperative follow-up. In conclusion, MRI emerges as a diagnostic tool complementary to other imaging techniques. However, in selected conditions--e.g., mediastinal struma and tumors--and in the postoperative follow-up, MRI can be considered the method of choice. PMID- 1509144 TI - [Incompetence of the m. gemellus veins in varicose veins: its incidence and phlebographic study]. AB - The authors report on 466 venographies of the lower limbs performed over the past 2 years on 412 patients affected with varicose veins. Pathologic reflux of the gastrocnemius veins was observed in 15.7% of cases: 9.7% in the group of non operated patients and 25.3% in the group with recurrent varicose disease. Ascending venography (and eventual popliteal venography) is the ideal diagnostic approach to show gastrocnemius veins incompetence, eventual anatomic variations, and isolated/associated incompetence of the short and/or long saphenous vein territory. Moreover, venography allows the hemodynamic evaluation, and shows reversed flow in the gastrocnemius veins in case of incompetence. PMID- 1509145 TI - [The hemodynamic significance of the angiographic changes after portasystemic shunting interventions for portal hypertension]. AB - Seventy-two patients (52 males and 20 females, mean age: 50.6 years) were studied. They had undergone distal splenorenal shunts according to Warren and its modifications for portal hypertension. All patients were examined with digital and/or conventional angiography preoperatively and 15 days postoperatively. Preoperative and postoperative angiography was employed to evaluate the changes in vessel diameters including the hepatic, splenic and superior mesenteric arteries, the splenic, superior mesenteric and portal veins; the length of the main axis of the spleen was also measured. Furthermore, the degree of hepatic portal venous perfusion was evaluated according to the degree of portomesenteric gastrosplenic disconnection. After surgery, the length of the main axis of the spleen is reduced and the hepatic artery diameter is increased, which are both signs of preserved hepatic flow and of reduced hypertension in the splanchnic venous system. The postoperative degrees of portal perfusion were correlated with the degrees of disconnection. In conclusion, the role is emphasized of early angiographic examinations after distal portosystemic shunts according to Warren to evaluate postoperative hemodynamic changes. PMID- 1509146 TI - [Double-contrast esophagography in the diagnosis of esophagitis due to Candida. A study on HIV-seropositive patients]. AB - This study was aimed at assessing the sensitivity of double-contrast esophagography in diagnosing Candida esophagitis. This condition accounts for 85% of all esophageal infections in the subjects suffering from AIDS. Thirty-nine HIV+ patients were evaluated: 19 of them had endoscopic diagnosis of Candida esophagitis. Our study confirmed the high sensitivity of esophagography (90%), as reported in the literature. Radiographic findings were edematous esophageal folds in the early stage and, subsequently, plaques and diffuse ulcerations. These patterns are suggestive of anatomical lesions: in the early stage, mucosal edema and erythema are observed, and later on pseudomembranes and ulcerations. None of our patients exhibited stenosis. All the subjects with Candida esophagitis had less than 250/mm3 of CD4 lymphocytes. In conclusion, double-contrast esophagography must be included in the periodic examinations performed on patients with AIDS, so as to allow an early diagnosis. PMID- 1509147 TI - [Intestinal tuberculosis. The radiologic aspects of a disease not to be overlooked]. AB - Intestinal tuberculosis still exists in the Western world, where it is usually underestimated and often mistaken for Crohn's ileo-colitis or cancer. The authors report the results of 4 cases of intestinal tuberculosis observed between 1983 and 1988. The cases are discussed in the light of the epidemiological data emerging from a review of recent medical literature. The danger is that the disease, which is endemic in Asian and African regions, may spread again in the Western world fostered by intensifying migrations of people and by the spreading of AIDS. According to recent experience, a negative chest film and Mantoux skin test no longer have a negative predictive value for intestinal tuberculosis. In the radiological differentiation from Crohn's disease it is useful to keep in mind some topographic features of TBC: the systemic non-discontinuous involvement of both sides of ileocecal junctions; the unusual presence of ileal lesions, with no cecal lesions, and localizations below the transverse colon. Useful differential morphological criteria can be: star-like or transverse ring-shaped profile of isolated ulcerations, tubular ileocolic junction with retracted cecum and open valve, and uniformity of lesion in the comprehensive picture of the clinical case. PMID- 1509148 TI - [The preoperative staging of rectal cancer with endorectal echography]. AB - The authors stress the value of the routine use of endorectal US for the preoperative staging of rectal cancer. This method accurately demonstrates the exact level of the lesion, the degree of circumferential invasion, the depth of local involvement and the extent of eventual spread beyond the rectal wall, the invasion of the surrounding structures and the presence of enlarged perirectal lymph nodes. A hundred and forty-one patients with rectal carcinoma located 3-16 cm from the ano-cutaneous line were examined with endorectal US preoperatively; a comparison was made between US findings and pathological data, so that a correlation could be made between US (uT) and histologic (pT) findings. A radial probe and a 7-MHz transducer were employed. Our results show US accuracy to be 93.6% with only 4 cases of understaging and 5 of overstaging. A hundred and twenty-nine patients who had undergone major surgery were also studied to evaluate US accuracy in lymph node detection: in 110 cases the actual lymph node status was correctly demonstrated; US diagnostic accuracy was 85.3% with 16 false positives and 3 false negatives. The correct evaluation of the actual local tumor spread, as demonstrated by endoluminal US, allows the choice of the correct treatment, together with a personalized therapeutic schedule, to reduce the incidence of local recurrences and to save, whenever possible, sphincter functionality. PMID- 1509149 TI - [New imaging with computed tomography in dental implantology]. AB - The authors report on a new image processing technique, for the imaging of both mandible and maxilla, which is very useful for oral specialists, especially in pre- and postoperative protocols for dental implants. After performing very thin axial scans (1-2 mm) with overlapping and without gantry tilt, of the mandible and/or maxilla, the data are reconstructed with a Elscint DentaCT software. With this program, multiple panoramic alveolar views can be obtained in a very short time (about 5 minutes), with a focal plane which can be easily modified by the operator; these planes are parallel to the curved axis of maxilla or mandible. Furthermore, the operator can get multiple images absolutely cross-sectional to the curved axis of alveolar regions (radial sections) and can image the number of cross-sectional planes and the distance between them. In all studied patients (41 over the last 6 months, 66 images overall), DentaCT yielded an excellent representation not only of all anatomical structures but also of every single implant; this allowed a complete preoperative planning based on morphovolumetric, densitometric and spatial data, together with the correct evaluation of implant positioning and of osteointegration success. PMID- 1509150 TI - [Small nodules of adenomatous hyperplasia in the cirrhotic liver. Treatment with percutaneous alcoholization]. AB - Small adenomatous hyperplastic nodules (AHNs) are now detected with increasing frequency in cirrhotic livers thanks to the widespread use of ultrasonography (US) in patients with chronic liver disease. The management of these lesions, which are commonly considered as likely to evolve into hepatocellular carcinomas (HCCs), is difficult: indeed, the surgical resection of a questionable neoplastic lesion does not seem advantageous, if surgical hazards are considered; on the contrary, the simple US/bioptic follow-up may be untimely in the detection of the malignant transformation. Percutaneous ethanol injection (PEI) under US guidance, already employed in the treatment of small HCCs, was recently proposed as a viable therapeutic alternative for AHNs. Our experience includes 16 AHNs submitted to PEI over a 2-year period. The size of the lesions ranged between 0.7 and 2.3 cm. Each nodule was treated on an outpatient basis with 6 weekly ethanol injections; the total amount of alcohol delivered to each lesion was 8-17 ml. No complications occurred. PEI induced volumetric reduction and/or structural modifications of the lesions; 10 of them were hardly differentiable from the surrounding parenchyma at the end of treatment. One month after PEI, CT allowed the detection of 13/16 AHNs; all of them resulted hypodense and showed no contrast enhancement. Repeated biopsies produced necrotic material in all cases. During the follow-up (10-33 months, mean 18.3) no recurrences were observed. At the moment, PEI seems to be the most appropriate therapeutic approach for small AHNs. PMID- 1509151 TI - [Renal echography in diabetes mellitus]. AB - The US findings in the kidneys of diabetic patients were studied. Diabetic subjects without clinical or laboratory signs of nephropathy were investigated by means of US in order to detect early anatomical lesions predictive of renal injury. The kidneys of cadaver diabetics were also studied to correlate US and histologic patterns. US alterations were observed in half of the cases: they were diffuse in 9% of cases and focal in 39%--hyperechoic spots and hyperechoic juxta medulla. Focal spots are more common in juvenile-onset diabetics and they are correlated with the age of diabetes. At histology the above US patterns were correlated with the vascular wall alterations typical of diabetic nephropathy. Diffuse alterations are not specific. The authors conclude by suggesting US as a prognostic test for diabetic nephropathy. PMID- 1509152 TI - [Magnetic resonance in the staging of renal carcinoma. The results compared with computed tomography in 42 cases]. AB - In order to investigate the value of MRI in the staging of renal cell carcinoma and to compare the results of MRI and CT, the authors evaluated by means of MRI and CT 42 patients affected with renal cell carcinoma. All patients underwent surgery, and pathology of the surgical specimens was performed. A comparison was made between the surgical and pathologic data and MRI and CT results. Moreover, a comparative evaluation of MRI and CT findings was also made. From the comparison between pathologic data and CT and MRI results MRI was seen to have correctly staged 36 of 42 cases (85%), versus CT 33 of 42 cases (78%). Moreover, MRI proved to be superior to CT in evaluating venous involvement (stages III A and III C) and extra-fascial tumor spread (stage IVA). On the contrary, no significant differences were found between MRI and CT in the evaluation of perirenal involvement (stages I-II) and lymph node metastases (stage III B). MRI misdiagnosed 6 of 42 cases: 2 false negatives in evaluating extracapsular tumor spread, 1 false positive of mesenteric infiltration, 1 false positive of renal vein thrombosis, 1 false positive and 1 false negative in evaluating lymph node metastases. CT misdiagnoses (9 of 42 cases) were the same as those of MRI in 5 cases, while in the MRI false positive of renal vein thrombosis CT was correct. The extant 4 incorrect CT findings were: 2 false positive of renal vein thrombosis, 1 false negative of infiltration of diaphragm and psoas muscle, 1 false positive infiltration of the right liver lobe. As yet, therefore, MRI cannot be routinely employed to stage all renal cancer patients. On the contrary, MRI should be considered as a second-choice diagnostic tool to employ in selected cases when CT alone cannot solve all the problems relative to staging. PMID- 1509153 TI - [A protocol for evaluating screen-film systems]. AB - When a competition is made for the supply of sensitive photographic material, each USL is asked, in a time scan of one or more years, to evaluate the characteristics of the screen-film systems proposed by the various companies. In the last years the authors had several opportunities to check different screen film systems for many Friuli-Venezia Giulia hospitals. For this reason they have set an evaluation form tested after following changes and recently employed in its final version. The check form is reported on in this paper with some personal considerations originated by the authors' experience. The technical parameters which must be evaluated are reported, together with the instrumentation needed to perform the technical examination, the examination modality, and the score attributing criteria. The evaluation form is very flexible for it allows each Radiology Department to evaluate each parameter in a personal way and to fit it to its own needs. PMID- 1509154 TI - Acute renal failure during the Korean War. AB - Oliguric ARF occurred in 0.5% of battle casualties who reached the field medical care system and raised their mortality expectancy from less than 5% to nearly 90%, due primarily to fluid volume overload and/or myocardial potassium intoxication. For their effective treatment the Renal Insufficiency Center with laboratory and a Brigham-Kolff rotating drum dialyzer began operations in 1952, as depicted in a videotape prepared for this presentation from motion picture footage filmed in early 1953. Our Surgical Research Team's major findings relevant to ARF were: (1) Renal function was depressed in most battle casualties in proportion to the severity of their wounds and blood loss. (2) Among the more severely wounded some developed nonoliguric; others, oliguric ARF. (3) Oliguria lasted from 3 days to 3 weeks without a discernible peak frequency of beginning diuresis at 10 days. (4) During oliguria, posttraumatic catabolism greatly accelerated extracellular accumulations of nitrogen, potassium, phosphate, and hydrogen ion with rapid, concurrent clinical deterioration. (5) Dialysis "on indication" produced an oscillating clinical and chemical course. (6) ARF was then revealed as a wasting disease complicated by infections, poor wound healing until diuresis occurred, anemia and bleeding, and hypertension during dialyses and in early diuresis. (7) The overall mortality rate was reduced. PMID- 1509155 TI - Acute renal failure in the Armenian earthquake. AB - A destructive earthquake devastated northwestern Armenia on December 7, 1988. The size of the affected area (radius of 50 miles), the time of the day when it occurred (11:41 a.m.), deficiencies in the design and construction of buildings, and inadequate initial rescue and relief capabilities resulted in one of the most lethal and traumatic natural disasters of the century. A large but unknown number (estimated at 225 to 385) of the extricated victims who had sustained crush injury developed myoglobinuric acute renal failure requiring dialytic support. The limited number (8-10 dialysis machines) of antiquated dialysis facilities available locally were overwhelmed. International dialysis relief efforts resulted in meeting the immediate acute needs and provided the motivation and elements of the more efficient system for the future delivery of maintenance dialysis. PMID- 1509156 TI - Acute renal failure in natural disasters. AB - Sudden-impact natural disasters such as earthquakes present a serious challenge to medical personnel in both developed and less developed countries. Crush syndrome with acute renal failure has been identified as a major medical complication that occurs among people whose limbs are trapped by heavy objects during natural disasters such as earthquakes or volcanic eruptions. Rescue and field medical teams should be trained to recognize and promptly treat the problems associated with prolonged limb compression and should carry the appropriate fluids and medications to treat the complications of traumatic rhabdomyolysis. Early, aggressive volume replacement followed by forced solute alkaline diuresis therapy may protect the kidney against acute renal failure. Better epidemiologic knowledge of the specific disaster conditions that predispose traumatic rhabdomyolysis to develop is clearly essential for those who must determine when emergency dialysis services are required in response to injuries sustained during natural disasters. Disaster health care personnel involved with providing emergency acute renal care should have a basic familiarity with disaster epidemiology in order to determine whether a given event requires their intervention. This paper includes recommendations for improving medical planning, preparedness, and response to natural disasters that cause acute renal failure. PMID- 1509157 TI - Energy metabolism and renal ischemia. AB - In renal preservation, the longer the organ is cold stored the greater the damage to the organ. The mechanism of hypothermic-induced kidney injury is not known. In this study the effects of long-term preservation (up to 120 h) of the dog kidney on mitochondrial functions in an homogenate of kidney cortex tissue was investigated. Kidneys were exposed to either warm ischemia (0 to 90 min) cold ischemia (0, 72, 96, and 120 h). The mitochondrial oxygen uptake was measured in an homogenate. In both warm and cold ischemia there were changes in the mitochondrial utilization of oxygen. The changes were characterized as a decrease in uncoupler stimulated oxygen uptake by up to 40%, an increase in oligomycin sensitive respiration by up to about 150%, and a decrease in the respiratory control ratio (uncoupler control ratio) from about 3 to 1. These changes in mitochondrial utilization of oxygen were partially reversed by including albumin in the respiration medium. Albumin binds free fatty acids and these may originate, during ischemia, from the action of phospholipases during ischemia. The changes in mitochondrial oxygen uptake may result from both the loss of membrane-bound phospholipids and the accumulation of free fatty acids. The changes in mitochondrial activity between 72 h (viable kidneys on transplantation) and 96 to 120 h preservation (nonviable kidneys) were not significant. Furthermore, reperfusion of kidneys preserved for 72 to 120 h resulted in a restoration of mitochondrial oxygen uptake to near normal (control) values. Thus, it does not appear that the limitation of successful long-term renal preservation is due to mitochondrial injury caused by cold ischemia. PMID- 1509158 TI - Free radical-mediated postischemic injury in renal transplantation. AB - Oxygen free radicals are generated during reperfusion of ischemic organs. Studies employing several species of laboratory animal (rat, dog, pig, rabbit, mouse) have documented protective effects of a variety of free-radical scavengers and antioxidants when administered before or immediately preceding reperfusion of ischemic kidneys. These protective agents include superoxide dismutase, dimethylthiorea, dimethyl sulfoxide, alpha-tocopherol, glutathione, the iron chelator deferoxamine, probucol, allopurinol and oxypurinol, and the spin trapping agent PBN. Furthermore, deficiency of antioxidants (selenium, alpha tocopherol, or catalase) exacerbates postischemic renal injury. These findings have been applied to renal transplantation in an attempt to decrease the incidence of posttransplantation acute renal failure. This is important because acute renal failure results in morbidity, increases hospital stay and the cost of transplantation, and complicates the use of cyclosporine. In porcine and in canine kidney transplantation, superoxide dismutase and allopurinol have provided renal protection. Transplantation is complicated because there may be prolonged hypoperfusion before harvesting plus a brief period of total ischemia during harvesting, followed by a prolonged period of cold ischemia and/or reperfusion, then followed by another brief period of ischemia and reperfusion during transplantation. Injury may occur at each of these phases by different mechanisms. PMID- 1509159 TI - Therapeutic implications of arachidonic acid metabolism in transplant-associated acute renal failure. AB - Acute renal failure is common in kidney transplantation due to immunologic, nephrotoxic, and ischemic events. In this paper the subject of posttransplant acute renal failure is reviewed in relation to arachidonic acid metabolism. Although experimental abnormalities noted in ischemia, rejection, and cyclosporin nephrotoxicity are discussed separately, it is obvious that in the clinical situation there is great overlap. The effects of altering the substrate arachidonic acid by feeding of dietary omega-3 fatty acids, both experimentally and clinically, are discussed. Finally, the limited clinical trials of prostaglandin analogues in renal transplant patients show conflicting conclusions as regards beneficial effects on rejection and renal function. Careful clinical studies of compounds with proven efficacy in animals are needed if acute renal failure posttransplant is to be modified or prevented. PMID- 1509160 TI - Osmotic diuretics and hemodilution in postischemic renal failure. AB - In the acute phase of ischemic renal failure, the severe depression of the glomerular filtration rate (GFR) is due to obstruction of the tubules by cells and cell debris rejected from the proximal tubules, a blockade which can be prevented at least partly, by treatment with osmotic diuretics. The isosthenuria, the second typical sign in ischemic acute renal failure, probably derives from the medullary ischemia that results from an intracapillary trapping of red cells. This, in turn, is suggested to be caused by oxygen-derived free radicals, which via increasing the capillary macromolecular permeability result in a massive extravasation of plasma and hence in hemoconcentration. As expected from this hypothesis, scavengers may ameliorate both the trapping and the consequent medullary ischemia. Unfortunately, however, a therapy using both osmotic diuretics and scavengers fails to improve the long-term outcome. Hemodilution would seem more promising, since it will both prevent the medullary ischemia seen in the acute phase and substantially improve the long-term outcome. At a hematocrit of 0.30, rat kidneys exposed to 45-min ischemia will show a GFR 1 month after the insult of more than 50% of the normal GFR as against 15% in untreated animals. PMID- 1509161 TI - Protective effect of dicalciphor during mitochondrial failure. AB - Mammalian cells differ considerably in the duration of anoxia which they can tolerate despite the fact that dramatic bioenergetic changes occur rapidly. Previous studies indicate that the ability to tolerate anoxia is at least partly due to an endogenous signal transduction system that senses O2 deficiency and signal altered ion transport functions in the mitochondria. The responses included inhibition of ATP synthase, ADP/ATP exchange, inorganic phosphate uptake, mitochondrial swelling, and loss of the mitochondrial proton-motive force. An important distinction between KCN toxicity and anoxia is that KCN does not elicit these protective mechanisms. Thus, the ability of a compound to elicit these mechanisms in KCN-treated cells provides an assay for potential agonists of the endogenous protective mechanisms. PMID- 1509162 TI - Renal vasculature and ischemic injury. AB - Functionally similar ischemic acute renal failure (ARF), as estimated by glomerular filtration rates (GFR), was induced by renal artery clamping (RAC) or intrarenal norepinephrine (NE) in rats and renovascular reactivity was examined at 1 week. With RAC-ARF induction there was total renal ischemia followed by abrupt return of renal blood flow (RBF). With NE-ARF induction there was subtotal ischemia (10-15% of basal RBF) with RBF recovery over several hours. Renovascular resistance (RVR) did not change to renal perfusion pressure (RPP) reduction in the autoregulatory range in RAC-ARF but paradoxically increased in NE-ARF. There was an exaggerated response to renal nerve stimulation in NE-ARF but no response in RAC-ARF. There was a vasoconstrictor response to intrarenal norepinephrine in the former but a negligible response in the latter. There was no vasodilation to acetylcholine in either group, but there was a normal response to prostacyclin in NE-ARF. Smooth muscle necrosis was found in 46% of resistance arterial vessels in RAC- but in only 8% of NE-ARF (p less than .001). When mean arterial pressure was reduced to 90 mm Hg for 4 h at 1 week, recurrent azotemia and fresh ischemic injury were noted in NE- but not RAC-ARF. It is concluded that different models of ischemic ARF induction result in different patterns of abnormal postischemic vascular reactivity. Differences in vascular smooth muscle and endothelial injury are due to differences in initial ischemia or rates of postischemic reperfusion. PMID- 1509163 TI - Glutathione and glycine in acute renal failure. AB - Glutathione is an important intracellular antioxidant in virtually all tissues, including the kidney. In the kidney, it has a rapid turnover in tubule cells and likely plays a role in any oxidant-related events which contribute to the tubule cell injury which occurs during acute renal failure. It was surprising, therefore, to find that the component amino acid, glycine, rather than glutathione itself, most strongly modulated the sensitivity of tubules cells to a variety of insults in several in vitro systems where these processes can be studied most directly. This paper reviews available evidence concerning the nature of both glutathione and glycine effects, their expression in vivo in in vitro, and their implications for understanding acute renal failure. PMID- 1509164 TI - Determinants of intrarenal oxygenation: factors in acute renal failure. AB - Oxygen tension within the renal parenchyma is influenced by two factors: metabolic demand and oxygen supply. There are three regions within the kidney in which there is an anatomical basis for limited oxygen availability. The first is the inner stripe where oxygen diffusion between arterial and venous vasa recta reduces PO2. The other two are the outer stripe and medullary rays which are fed by O2-poor blood from venous vasa recta. The balance between oxygen demand and supply is most critical in the inner stripe where the PO2 is most influenced by transport activity. In contrast, altering transport activities in the outer stripe will not change the prevalence of hypoxic S3 injury but will alter its type (i.e., cell fragmentation related to high GFR and increased workload versus cell edema related to low GFR and minimal workload). The effect of transport activity on medullary ray PO2 has not been well defined. Using sensitive oxygen microelectrodes, cortical PO2 (52 +/- 2 mm Hg) in the rat was found to be higher than medullary PO2 (21 +/- 2 mm Hg, p less than 0.001). How are these observations reflected in current models of acute renal failure? The ischemia reflow model affects proximal tubules with a predilection for S3 (located within the outer stripe of medulla) after short-term ischemia. With hyperfiltration (induced by glycine or renal hypertrophy) and the pursuant increase in transport related O2 demand, hypoxic mTAL inner stripe injury becomes prominent. Renal parenchymal hypertrophy exaggerates injury in the contrast nephropathy model, in which mTAL inner stripe injury is a predominant feature and medullary PO2 is very low.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1509165 TI - Calcium channel blockers: protective effects in ischemic acute renal failure. AB - Studies in heart, liver, and kidney have provided evidence that calcium is an important factor in cell injury. Calcium channel blockers are used with increasing frequency in ischemic and toxic renal failure. In this review the available data on the effects of calcium channel blockers in animal models of ischemic renal failure are presented and possible mechanisms of protective actions are discussed. PMID- 1509166 TI - The long-term outcome of postischemic acute renal failure in the rat. PMID- 1509167 TI - Heme protein-ischemic interactions at the vascular, intraluminal, and renal tubular cell levels: implications for therapy of myoglobin-induced renal injury. PMID- 1509168 TI - Drug-phospholipid interactions: role in aminoglycoside nephrotoxicity. AB - Aminoglycoside antibiotics are known to be transported and accumulated within lysosomes of renal proximal tubular cells and to cause proximal tubular cell injury and necrosis. The pathogenesis of aminoglycoside nephrotoxicity is postulated to be related to the capacity of these organic polycations to interact electrostatically with membrane anionic phospholipids and to disrupt membrane structure and function. Aminoglycoside antibiotics have been shown to bind to anionic phospholipids of model membranes and to alter membrane permeability and promote membrane aggregation. In vivo these drugs induce phospholipiduria and a renal cortical phospholipidosis. The latter reflects the accumulation of phospholipid-containing myeloid bodies within the lysosomal compartment consequent to aminoglycoside-induced inhibition of lysosomal phospholipases. The mechanism of drug-induced inhibition of phospholipases has been shown to be secondary to the binding of these cationic drugs to anionic phospholipids. As the lysosomes became progressively distended with myeloid bodies, they become unstable and eventually rupture, which results in the release of acid hydrolases as well as high concentrations of aminoglycosides into the cytoplasm where they interact with and disrupt the function of other membranes and organelles including mitochondria and microsomes. It is postulated that the redistribution of drug from the lysosomal compartment to organellar membranes is the critical event which triggers the irreversible injury cascade. Polyaspartic acid is a polyanionic peptide which when administered in vitro or in vivo forms electrostatic complexes with aminoglycoside antibiotics and prevents these drugs from interacting with anionic phospholipids, from perturbing phospholipid metabolism and from causing cell injury and necrosis. PMID- 1509169 TI - Alterations of membrane fluidity by toxic injuries. AB - Alterations in membrane fluidity affect, via an effect on the ease with which proteins may change conformation, the activity of various enzymes and transport systems. Recent experiments have shown that toxic injury is frequently associated with modifications in physical state and/or lipid composition of plasma membranes. Such modifications are likely to play a role in cell dysfunction, especially in epithelial cells whose optimal function depends on the polarity in membrane fluidity between apical and basolateral domains. PMID- 1509170 TI - Renal proximal tubule cell cultures for studying drug-induced nephrotoxicity and modulation of phenotype expression by medium components. AB - The characteristics of two established renal cell lines (LLC-PKI and OK) and of primary cultures of rabbit and human proximal tubule cells are described by summarizing the literature about specific properties retained by these cells in culture. Furthermore, comparative biochemical and functional properties are presented including both specific marker enzymes and transport properties of these cells grown in various media. The impact of culture medium composition on the expressed cellular phenotype is discussed and its consequences on the profile of toxic response due to aminoglycoside antibiotics is analyzed. The in vitro nephrotoxicity of three platinum-containing coordination complexes which exhibited different in vivo nephrotoxic potentials is studied by another technique in a model of rabbit proximal tubule cells in primary cultures in order to correlate results to in vivo data and to define reliable and sensitive parameters for the assessment of platinum-derivative-induced nephrotoxicity. Although animal cell lines have been established in serum-supplemented medium, LLC-PK1 and OK cells as well as primary cultures of proximal tubules are successfully grown in hormonally defined medium, the standardization of which is better controlled for nephrotoxicity studies. PMID- 1509171 TI - Mild oxidative stress: cellular mode of mitogenic effect. PMID- 1509172 TI - Acute renal failure secondary to leukocyte-mediated acute glomerular injury. AB - Acute glomerulonephritis can cause acute renal failure. Activated neutrophils and monocytes are major effectors of glomerulonephritic renal failure. Adhesion molecules, granule enzymes, reactive oxygen radicals, lipid metabolites, and cytokines of activated neutrophils and monocytes mediate glomerular capillary constriction, occlusion, and destruction. Injurious products and biologically active mediators released by activated leukocytes have profound functional effects on mesangial cells and endothelial cells, which in turn participate in the disturbance of glomerular function, for example, by altering capillary diameter and surface area. The glomerular inflammatory events result in decreased glomerular capillary ultrafiltration coefficient and glomerular filtration rate, as well as other functional perturbations. PMID- 1509173 TI - Inflammatory mediators in glomerular injury. PMID- 1509174 TI - Glomerular coagulation system in renal diseases. AB - Glomeruli possess a complex hemostasis system with prothrombotic (procoagulant, antifibrinolytic) and antithrombotic (anticoagulant, fibrinolytic) properties that can act locally on platelet adhesion or aggregation, on plasmatic coagulation pathways, and on fibrinolysis. In vitro, inflammatory mediators, such as TNF, favor glomerular thrombogenic properties through enhancement of thromboplastin synthesis and of plasminogen activator inhibitor PAI-1, and through decrease in thrombomodulin activity. In some diseases, intraglomerular fibrin formation appears to be favored by increased glomerular prothrombotic properties, for example: augmented thromboplastin activity in immune glomerulonephritides and in Shwartzman phenomenon, excessive thromboxane A2 synthesis, and decreased fibrinolytic activity in severe renal allograft rejection. In other diseases glomerular hemostasis appears to function homeostatically, for example, in thrombin-induced disseminated intravascular coagulation with enhancement of fibrinolytic activity favoring fibrin dissolution. Novel methods allowing the study of glomerular hemostatic activities in renal biopsy fragments should help to understand the mechanisms of fibrin deposition in human diseases and to treat it on a logical basis. PMID- 1509175 TI - Bacterial and enzymatic bioassays for toxicity testing in the environment. AB - Microbioassays using bacteria or enzymes are increasingly applied to measure chemical toxicity in the environment. Attractive features of these assays may include low cost, rapid response to toxicants, high sample throughput, modest laboratory equipment and space requirements, low sample volume, portability, and reproducible responses. Enzymatic tests rely on measurement of either enzyme activity or enzyme biosynthesis. Dehydrogenases are the enzymes most used in toxicity testing. Assay of dehydrogenase activity is conveniently carried out using oxidoreduction dyes such as tetrazolium salts. Other enzyme activity tests utilize ATPases, esterases, phosphatases, urease, luciferase, beta-galactosidase, protease, amylase, or beta-glucosidase. Recently, the inhibition of enzyme (beta galactosidase, tryptophanase, alpha-glucosidase) biosynthesis has been explored as a basis for toxicity testing. Enzyme biosynthesis was found to be generally more sensitive to organic chemicals than enzyme activity. Bacterial toxicity tests are based on bioluminescence, motility, growth, viability, ATP, oxygen uptake, nitrification, or heat production. An important aspect of bacterial tests is the permeability of cells to environmental toxicants, particularly organic chemicals of hydrophobic nature. Physical, chemical, and genetic alterations of the outer membrane of E. coli have been found to affect test sensitivity to organic toxicants. Several microbioassays are now commercially available. The names of the assays and their basis are: Microtox (bioluminescence), Polytox (respiration), ECHA Biocide Monitor (dehydrogenase activity), Toxi-Chromotest (enzyme biosynthesis), and MetPAD (enzyme activity). An important feature common to these tests is the provision of standardized cultures of bacteria in freeze dried form. Two of the more recent applications of microbioassays are in sediment toxicity testing and toxicity reduction evaluation. Sediment pore water may be assayed directly or solvents may be used to extract the toxicants. Some of the solvents used for extraction of organic chemicals are themselves toxic to bacteria (e.g., dichloromethane), requiring exchange with a less toxic solvent (e.g., ethanol, methanol, DMSO). A modification of the Microtox test allows direct assay of solid-phase samples such as sediments. The toxicity reduction evaluation (TRE) must be carried out at wastewater treatment plants whose effluents fail toxicity standards. The TREs require numerous and repeated toxicity assays, thus favoring application of microbioassays. Presently, no single microbioassay can detect all categories of environmental toxicants with equal sensitivity. Therefore, a battery of tests approach is recommended. The differential sensitivity of alternative tests may, in fact, be exploited. Further research is needed to construct strains of genetically engineered microorganisms or isolate microorganisms or enzymes that respond to specific classes of toxicants. These can be combined into batteries appropriate for different environments or test objectives. PMID- 1509176 TI - Environmental cadmium in Europe. AB - The present article reviews information from the latest 10 years concerning fate and exposure of cadmium in the environment, on ecotoxicological effects, and on critical pathways leading to human and environmental exposure. It emphasizes the situation within the Community of European Countries by referring to limit values used in the EEC and some of its member states for emissions to water, air and soil. Estimates have been made on total emission balances for the Netherlands, Denmark, and for the EEC as a whole. The balances show that 70-90% of all cadmium circulating in the Community is disposed of as waste in solid waste deposits. Production and use patterns are presently changing, as indicated by reduced consumption in recent years of cadmium for plating, stabilizers and pigments in several countries as a result of regulations. However, significant increases in consumption for cadmium-containing batteries have occurred, resulting globally in increasing trends for the total consumption and production. Cadmium in sediments is more mobile than described earlier. Aquatic organisms can be classified in order of decreasing accumulation: algae greater than molluscs greater than crustaceans greater than fish. There is no evidence of biomagnification of cadmium within marine or fresh water food webs. Cadmium may enter into plants via roots or by foliar adsorption following atmospheric deposition. Biomagnification in terrestrial food chains is not observed. The uptake into plants is plant specific. Within plants significant variations are seen with concentrations generally decreasing in the order: roots greater than leaves greater than fruiting parts greater than seeds. A compilation of cadmium in air, in the aquatic environment and in soil is given. A downward trend during the 1970s to mid-1980s seems to be evidenced from various Northern European studies on cadmium air concentrations as well as for deposition rates of cadmium. In rivers, the dissolved cadmium concentrations are generally found to be relatively low (10-500 ng/L). In seawater, cadmium concentrations are found at 0.5-10 ng/L in oceanic or open marine areas, while elevated concentrations are reported in more closed marine areas and especially in coastal zones close to polluted estuaries. In fresh water, lake sediments concentrations 3-30 times higher than the background concentrations are reported in the surface layers of sediments. A significant decrease in such pollution has been observed within the recent 10 years. For marine sediments, enrichment factors of two are found in sediments from open areas and locally even 5-10 times.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1509177 TI - Schedule-induced stereotypy. AB - The phenomena of the induction and entrainment of adjunctive behaviours was investigated in eight people with severe or profound mental retardation who exhibited stereotypic behaviours. The occurrence of collateral behaviours was investigated under extinction and massed reinforcer baselines and a variety of periodic or intermittent schedules of reinforcement for the performance of a simple experimental task. Seven of the eight subjects demonstrated evidence of schedule-induced stereotypic behaviour in the experimental conditions: five of the eight subjects also showed evidence of the entrainment of these behaviours within the first third of the interreinforcement interval. The results are discussed in relation to the analysis and intervention of problem behaviours in people with severe or profound mental retardation. PMID- 1509178 TI - A comparative analysis of general case simulation instruction and naturalistic instruction. AB - Effects of naturalistic instruction and simulation instruction for the acquisition, generalization, and maintenance of housekeeping and janitorial work skills in young adults with moderate and severe mental retardation were assessed. The performance of the four participants (under the two methods of instruction for two job task sequences) was assessed using a multiple probe design across behaviors. Both the naturalistic and simulation instructional methods involved noninstructional probes, instruction sessions, generalization probes, and withdrawal of instruction. Results of noninstructional probes parallel to simulation instruction sessions indicated only a minimal improvement over initial (base-line) noninstructional probes. By contrast, noninstructional probes parallel to naturalistic instruction showed a marked improvement for all four participants with correct responding reaching or exceeding the 90% level. Naturalistic instruction was an effective means of producing skill acquisition, while generalization of the learned skill was marginal. PMID- 1509179 TI - A case of phenobarbital exacerbation of a preexisting maladaptive behavior partially suppressed by chlorpromazine and misinterpreted as chlorpromazine efficacy. AB - An adult female with developmental disability was prescribed chlorpromazine for the target behaviors of aggression and self-injurious behavior (SIB), and she was prescribed phenobarbital for seizures. Upon a chlorpromazine minimal effective dose reduction, target behaviors increased and dosage was returned to prior levels with the conclusion that chlorpromazine was controlling the target behaviors. Upon subsequent reduction and discontinuation of phenobarbital, however, chlorpromazine was able to be reduced with no increase in target behaviors. Ten years of behavioral data are presented to support the hypothesis that phenobarbital was exacerbating maladaptive behaviors. Given tardive dyskinesia (TD), clinicians and interdisciplinary teams should remain alert to the following client profile: (1) prescribed phenobarbital (or primidone), (2) prescribed neuroleptics, especially at high dosages, to control maladaptive behaviors, (3) failure of neuroleptic gradual minimal effective dose attempts, and (4) possible presence of behavioral procedures, especially intrusive procedures, to control maladaptive behaviors. This profile should trigger a "red flag" as to the possibility of phenobarbital behavioral side effects or exacerbation of preexisting maladaptive behaviors. PMID- 1509180 TI - Differential reinforcement as treatment for behavior disorders: procedural and functional variations. AB - For many years, differential reinforcement has been a prevalent and preferred treatment procedure for the reduction of behavior disorders. This paper reviews the procedural variations of differential reinforcement and discusses their functional properties. It is proposed that such procedures are more likely to be successful if behavioral function is a primary consideration in prescribing treatments; furthermore, limited success noted in previous research may be due to the arbitrary relationship that often exists between reinforcers and target behaviors when behavioral function is unknown. Despite the promise of a function based approach to differential reinforcement, several current limitations exist in the identification and manipulation of relevant variables. Thus, further research is required to elucidate the relationship between aberrant behaviors and the variables responsible for maintaining them; otherwise, successful treatment cannot be expected. Several areas for future research are discussed conceptually as extensions of current and past experimentation. PMID- 1509181 TI - [The visco-elastic behavior of the respiratory system during mechanical ventilation. Interpretation with the aid of a model]. AB - The purpose of this review is to present an approach to the visco-elastic properties of the respiratory system in the mechanically ventilated patient through the method of occlusion of the airways at a constant inspiratory flow rate. The ideas of airways resistance, tissue resistance, static and dynamic elastance are defined from the theoretical point of view and also from the point of view of the occlusion method. A large part is given to the bicompartmental model describing the visco-elastic properties of the lung and of the thoracic wall. Recently carried out experimental studies both in healthy man and in disease have given results which seem to confirm the predictions made by this model. According to this system the lungs may be represented as a homogenous whole surrounded by visco-elastic components. PMID- 1509182 TI - [Physiopathological bases for retraining programs of asthma patients: adjustment to rehabilitation]. AB - Despite current discussions promoting physical and sports activities in asthmatics, no studies have yet been done on the possible pathophysiological justifications for rehabilitation by sports programs. Consequently asthmatics are retrained in an empirical fashion and the assessment of these programs is subjective. The aim of this article is thus to review the different studies concerning the adjustment of asthmatics to muscular exercise and to deduce from these what could or should be the pathophysiological objectives of reconditioning protocols. The principal ideas which emerge from this study derive from three fundamental facts: 1) the training of asthmatics should be based on an individual approach since clinical severity leads to very unequal adaptations during muscular exercise; 2) it is advisable to strive against the declining physical fitness of the asthmatics, which is responsible for the accelerated functional deterioration, disturbances of psychomotor development and an increased risk of exercise-induce asthma; 3) the decrease of excessive exercise hyperventilation is, from the evidence, the greatest priority among the pathophysiological objectives, because hyperventilation is a principal cause implicated in the disturbance of cardiovascular adjustments to effort by heart-lung interaction. PMID- 1509183 TI - [Pharmacology of nicotine]. AB - Nicotine has a small molecular weight and is absorbed via the mucosa (Guccal or nasal), the pulmonary alveoli and the skin. The phenomenon of autotitration explains how a dependent smoker can unconsciously change his method of smoking to maintain a steady nicotine level. Nicotine leads to a liberation of catecholamines by acting on the nervous system through the intermediary of nicotine receptors. There is increased vigilance and powers of intellectual concentration, an awakening reaction and some anxiolytic and euphoriant effects. From the cardiac stand point there is an increased heart rate and blood pressure, as a result of the sympathomimetic effects. Elimination is via the kidneys as unchanged nicotine, cotinine and 1'-N-oxide of nicotine. Nicotine has an addictive action and is capable of inducing pharmacological dependency, tolerance and withdrawal syndrome in cases of abrupt cessation. A knowledge of the pharmacology of nicotine is important in the process of stopping smoking. PMID- 1509184 TI - [Diffuse infiltrative lung diseases: histological support of elementary lesions observed on tomodensitometry]. AB - High resolution computed tomography (TDM-HR) is now the technique of choice in the diagnosis and management of diffuse infiltrative lung disease (PID). After a brief review of the technique the authors describe the normal appearance; anatomical observations and the in vivo findings have shown that TDM-HR allow for the exploration of details of structure down to the second pulmonary lobule. Thus, through the alterations that are transmitted in the lobular area, and from its contents and its limits, PID has led to the elaboration of a new semeiology. The authors review the basic computed tomographic images and correlate these in each case with the histological evidence. The spatial distribution and the time sequence of the elementary images are the two other terms in the diagnostic equation of PID. The spatial distribution of several elementary images presents in TDM-HR a superior aetiological pointer to that which is furnished by thoracic radiographs; and the time sequence may furnish a useful indication as to the progress of the treated disease. Sarcoidosis, histiocytosis X, idiopathic interstitial fibrosis and lymphangitis carcinomatosis would serve as examples. Nevertheless, the authors point out that it would be dangerous during the period of evaluation to prematurely extend to all cases of PID conclusions which are only possible to make at present in a restricted number of disorders. PMID- 1509185 TI - [Local immune response in allergic asthma]. AB - The key issue in asthma research is allergen capture and presentation. An increase in understanding in this area may result in the development of new types of therapeutic drugs, although at present there remain a number of points to be elucidated. In this paper, we review recent research in this field. Allergens are small air-conducted soluble antigens which are capable of inducing a specific immune response characterized by a significant synthesis of IgE. The allergen passes through the bronchial epithelium and specialized antigen presenting cells (APC) capture and present the antigen to T-cells, causing their activation via an interaction with class II MHC molecules on the APC. Allergens are also capable of activating other cell types and the subsequent release of inflammatory mediators, chemoattractants and cytokines may result in bronchial inflammation which is one of the cardinal signs of asthma. PMID- 1509186 TI - [Respiratory function in heroin addicts with or without HIV infection. Study of 107 cases with a 6-month follow-up of 36 subjects]. AB - Both intravenous drug addiction (IVDA) and HIV infection can involve respiratory system. So, we have studied pulmonary function in 107 heroin abusers during deprivation to clarify the extent of these two factors respectively. Two groups were separated: 50 subjects without HIV infection (HIV-) and 57 seropositive subjects (HIV+) in early stage of the disease (mean CD4 lymphocytes: 457 +/- 61/mm3). 36 subjects have been investigated 6 months later to evaluate the reversibility of possible observed abnormalities. Altered pulmonary function was encountered similarly in HIV+ and HIV-. DLco was abnormal in 40% of cases both in HIV+ (mean DLco: 63.4 +/- 1.1% of predicted values) and HIV- (mean DLco: 65.4 +/- 1.5% pred); obstructive lung disease was present in 18% of HIV- (FEV1/VC: 63.8 +/ 2.5) and 9% of HIV+ (FEV1/VC: 61 +/- 3.6); restrictive lung disease was found more frequently (16% vs 10%) in HIV+ (FEV1/VC: 81.2 +/- 2.1, TLC: 72.4 +/- 3.6% pred) than in HIV- (FEV1/VC: 84.2 +/- 1.6, TLC: 71.2 +/- 0.9% pred). These abnormalities were not associated with significant arterial blood gas modifications. As a whole, DLco tend to improve in the two groups and this significantly for HIV+ (p less than 0.03). But for individuals initial DLco alteration was persistent in 68% of cases suggesting slow improvement. In conclusion, in this study HIV+ and HIV- IVDA were not different concerning pulmonary function. In this risk group, DLco itself had a poor specificity and only it follow-up may be of interest for pulmonary opportunistic infection screening. PMID- 1509187 TI - [Pulmonary lesions in Wegener's disease. Report of the French Anatomo-clinical Research Group. Study of 40 pulmonary biopsies]. AB - We report the results of a morphological analysis of 60 pulmonary biopsies gathered from a multi center study, organised by the clinico-pathological research group on Wegener's Disease under the auspices of the French Language Society of Thoracic Medicine. Forty of the sixty cases analysed were retained after indexing the histological aspects in order to specify their diagnostic value. Two groups of lesions were distinguished, which had different significance. Group A: These include the three major diagnostic criteria, which reinforce one another as they associate: 1) The polymorphoneutrophil microabscesses with limited central necrosis or an extended necrosis like the contours of a relief map. 2) An angiitis (arteries, veins, capillaries) with eccentric focal parietal crescent-shaped microabscesses. 3) Polymorphous granulomas with giant cells. Group B: In this group are the minor morphological observations (table II) of a lesser value and significance. 1) Acute or chronic lesions with alveolar haemorrhage, endogenous lipid pneumonia, xanthomatous granulomas, an organising pneumonia with an alveolitis. 2) Bronchial lesions: Bronchitis and necrotising bronchiolitis, which is more rarely follicular. 3) Sero-fibrinous or infiltrative neutrophil pleural lesions with focal microabscesses, elastolysis and elastophagia with giant cells in the elastic lamina. Thirteen cases presented with misleading lesions, which was a possible source of diagnostic error and led to a discussion of several associated disorders (Goodpasture's syndrome, and collagen disorder syndrome) or there may be systemic angiitis (Giant cell or lymphocytic) or also systemic or tissue eosinophilia (Churg-Strauss syndrome, bronchocentric granulomatosis) or necrotising bronchitis (atrophic polychondritis) or other forms of nodular interstitial fibrosis, such as histiocytosis X. We would like to stress the great polymorphic variation of the lesions and the difficulties which confront pathologists in the diagnosis of Wegener's Disease, above all when it is localised to the lung. There is value in finding at least one major diagnostic criteria which is associated with a minor criteria and with the help of the C.ANCA levels may lead to a narrow clinicopathological correlation and allows for a fairly precise approach to the diagnosis and identification of early or unusual lesions and thus to the early treatment of patients before irreversible renal failure appears. PMID- 1509188 TI - [Detergent enzymes: has the risk of occupational sensitization disappeared?]. AB - Occupational allergy to enzyme detergents had almost disappeared by the use of preventive measures, both individually and in industries. The occurrence of 8 new cases of asthma in a detergent factory has led to a prospective clinical and aetiological enquiry. Although there was no documentation using the specific provocation test or by measuring respiratory function whilst at work, the occupational character of this asthma seemed possible after taking a history. Sensitization to the enzymes used (Savinase, Maxatase and Biozym P 300 S) was shown by skin tests (8 positive to all the enzymes) and the level of specific IgE to Rast (8 times greater than class 3 for Savinase and Maxitase) and for HBDT for Maxatase and Biozym P 300 S (greater than 50% in 8 patients). From another stand point the incomplete application of preventive measures within the factory did not seem to totally explain the origin of this sensitization. In fact, it was the study of the morphology of the enzyme grains, which had been introduced into the factory which helped us to explain the mechanism. In effect it was the capsules of the grain which were fissured and thus allowed allergen contact. The replacement of these grains whose envelope was intact, led to the disappearance of the symptoms and confirmed our hypothesis. There remains a continuing risk from occupational sensitization to asthma and it is suggested that there is continued collaboration between the medical profession and industry. PMID- 1509189 TI - [Comparative epidemiological characteristics of a homogeneous series of acute common pneumopathies seen in a general hospital center (GHC)]. AB - Between 1979 and 1989, 108 cases of community acquired pneumonia in non immunodepressed subjects were admitted to hospital to a specialist chest department. The patient's characteristics were as follows: mean age = 56 (range 14-91), 44 women and 64 men. The causal agent was isolated in 44 cases (40%) of which 4 cases were viral (9% of 44 cases) and 12 were Legionella (27%), pneumococci (SP) 11 cases (25%), Mycoplasma pneumoniae (MP) 8 cases (18%), and Chlamydia 8 cases. The microbacteriological criteria for diagnosis were as follows: significant seroconversion for viruses, MP, Chlamydia, Legionella, bacteriological isolation on blood cultures, and pleural liquid for SP. In 64 cases the bacteriological diagnosis was not established. In this series we note as follows: 1) There did not appear to be any seasonal peak in relation to bacteria isolated, contrary to previous reports, in particular for Legionella. On the other hand viruses occur notably in February and March. 2) Chlamydia were more frequent in individuals living in rural areas; 7 cases out of 8. Whereas amongst the 108 patients 55 were from the country and 34 from the city (16 from institutions and 3 uncertain). In conclusion, if the level of bacteriological identification (IMB) appears weaker than in previous reference series: 51-65%, the diagnostic yield clearly improved in our experience achieving results nearer to the best achievable: 54% of IMB from 48 cases which were recruited between 1985-1989.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1509191 TI - [Acquired rifampicin resistance during M. kansasii infection in a patient with AIDS]. AB - A man with AIDS and M. kansasii lung infection received rifampicin and isoniazid for 9 months, combined with ethambutol for four months. The treatment was effective with sputum culture negativation, but relapse occurred. The minimal inhibitory concentration of rifampicin for the M. kansasii strain was respectively 0.2 microgram/ml at the onset and 128 micrograms/ml after the treatment, giving evidence of acquired resistance. A new treatment was initiated but is was ineffective. PMID- 1509190 TI - [Sequential administration of a reduced dose of almitrine to patients with chronic obstructive bronchopneumopathies. A controlled multicenter study]. AB - Recent multi-centre studies have shown that high doses of Almitrine (100-200 mg per day), lead to a significant improvement in the hypoxaemia of patients presenting with chronic airflow obstruction, but that a high blood level (greater than 500 ng/ml) is often seen after 1 year, sometimes associated with signs of peripheral neuropathy. In order to maintain Almitrine blood levels in the range 200-300 ng/ml we have used an intermittent regime (with a "window" of 1 month every 3 months) and a dose limited to 100 mg per day. 102 hypoxic patients with chronic airflow obstruction, who were in a stable state were included. 65 patients were in the Almitrine group (A) and 37 patients in the placebo group (P). The treatment lasted for 1 year. In addition there was a 3 monthly follow up with arterial blood gases and spirometry, a clinical neurological examination and also electrophysiology, initially and after 6 and 12 months. 43% of patients in group A and 32% of patients in group P, left the study, most often due to poor cooperation, but sometimes as a result of side effects. After 12 months the PaO2 rose significantly in group A from 59.1 +/- 0.7 to 65.8 +/- 1.6 mmHg (p less than 0.001) whilst it was not changed in group P. The PaCO2 did not change in either group. On the other hand there was a significant fall in the subgroup of patients with hypercapnia in group A (p less than 0.001). The outcome of the neurological and electrophysiological assessments did not show any significant difference between the two groups.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1509193 TI - [Occupational asthma caused by ebony wood]. AB - A case of occupational asthma to ebony wood dust is described in a violin and stringed instrument maker, who was sanding and filing ebony to make the finger boards of violins and cellos. The diagnosis was confirmed using a realistic provocation test; after sanding and smoothing the ebony for 20 minutes the patient developed bronchial spasm with fall of the force expired volume in one second (VMS) of 45% which was reversible following the inhalation of beta 2 agonists. A delayed reaction was seen at 3 hours and 6 hours and at 20 hours after the test. The observations of occupational asthma or rhinitis to ebony wood are very rare. To our knowledge there are two publications at the present time. It has been recognised as an occupational disease (see table 47 of occupational diseases) and an exclusion order has been effected. PMID- 1509192 TI - [Primary liposarcoma of the mediastinum: contribution of MRI to the diagnosis. Apropos of a case]. AB - An exceptional case of liposarcoma arising in posterior mediastinum is reported in a young woman. CT fails in diagnosis because no area of fatty density was found. MR features were suggestive of this etiology. PMID- 1509194 TI - [Allergic alveolitis due to colophony]. AB - We report the observation of a 37 year-old female worker exposed for 5 years to heated colophony fumes. The patient used a soldering iron with colophony flux cored solder. She presented with chronic cough and dyspnoea on exertion without any wheezing. Clinical evidence associated with chest X-ray, lung function tests, lymphocytic alveolitis in bronchoalveolar lavage led to hypothesize the diagnosis of an occupational alveolitis linked to colophony exposure. This was eventually confirmed by coupling repeated lung function tests and bronchoalveolar lavages with on-off periods of occupational exposure. PMID- 1509195 TI - [Adenocarcinomatous pleural lesion associated with hypoglycemia]. AB - We report the case of a patient suffering from a glandular pleural lesion. The evolution of the disease was punctuated by periods of hypoglycaemia, which caused a coma. There was no clinically evident explanation for these hypoglycaemic episodes. Investigations revealed adrenal failure, but this adrenal failure was unrelated to the neoplastic process in the patient. This case is a reminder that the cause of hypoglycaemia associated with tumours can really have a paraneoplastic origin and justifies an in depth study to achieve an aetiological diagnosis. PMID- 1509196 TI - [Infections of the respiratory tract. October 18, Lille. 4th consensus conference on anti-infective drugs]. PMID- 1509197 TI - Effects of multiple doses of moricizine hydrochloride on its pharmacokinetics and hepatic microsomal enzymes in rats. AB - We studied the influence of chronic moricizine hydrochloride (MRZ) treatment on the drug's pharmacokinetics and on drug metabolizing enzyme activities in rats. Separate groups of 8 rats (4 males and 4 females) were treated with 40 and 100 mg/kg oral MRZ once daily for 7 days and saline control for 7 days prior to the preparation of hepatic microsomal enzyme suspensions. Depending on the substrate, treatments with multiple oral MRZ increased or decreased hepatic microsomal enzyme activities. For the pharmacokinetic study, rats (4 males and 4 females) were treated with 40 mg/kg oral MRZ once daily for 7 days. A comparison of MRZ pharmacokinetics obtained on day 1 relative to day 7 revealed that both AUC0-t and AUC0-infinity increased about 7-fold in males and 2-fold in females. Cmax also increased about 5-fold from day 1 to day 7 in males. These increases in blood concentrations and AUC's are likely due to enzyme inhibition. Results obtained from female rats on days 1, 4 and 7 suggest that metabolic changes probably occur after the 4th day of dosing. Therefore, chronic MRZ treatment affected its pharmacokinetics and hepatic metabolizing enzyme activities in rats. PMID- 1509198 TI - Inhibitory effect of methylprednisolone suleptanate (U-67590A) on anaphylactic bronchoconstriction in guinea pigs. AB - Effects of U-67590A, an analogue of methylprednisolone, on antigen-induced bronchoconstriction expressed as ventilation overflow were examined in ovalbumin sensitized guinea pigs. When administered intravenously 17-18 hr before the challenge with antigen, U-67590A at doses of 10 and 30 mg/kg caused dose dependent inhibition of increased ventilation overflow immediately after challenge. Death due to anaphylactic shock was markedly reduced by U-67590A. At 10 mg/kg (i.v.), U-67590A given 10 min before the challenge significantly inhibited the antigen-induced increase in ventilation overflow; the greatest inhibition seen 5-6 hr prior to the challenge. Pretreatment with 10 mg/kg FPL 55712 attenuated the increase in ventilation overflow during anaphylaxic shock. It is conceivable that inhibition of the leukotriene-mediated response is involved in the glucocorticoid-induced suppression of airway obstruction in anaphylaxis, and that inhibitory action of the glucocorticoid directly acting on the airway may account for the very fast onset of action. PMID- 1509199 TI - Variations of lipid profile in animals caused by adenosine analogs: N6 (amido-3 propyl) adenosine hydrochloride and (carboxamido-3-propylamino)-6-(triproprionyl) 2',3',5'beta (D-ribosyl)-9-purine. AB - N6-substituted adenosine analogues are powerful inhibitors of lipolysis in the adipose tissues of animals and humans, because of their agonist effect on A1 purine receptors. Using a model of hypertriglyceridemia provoked by intravenous injection of Triton WR 1339, we observed that Agr 529 [N6(amido-3 propyl)adenosine hydrochloride] at 2 mg.kg-1 intravenous in rabbits, and intraperitoneally and orally in rats led to a return of the levels of circulating triglycerides to normal values. In addition, Agr 529 and its prodrug, Agr 540 [(carboxamido-3-propylamino)-6-(triproprionyl)2', 3',5'beta(D-ribosyl)-9-purine] administered to rats at 3 and 30 mg.kg-1, respectively, returned plasma triglyceride concentrations to normal levels. Intravenous administration of Agr 529 to normal rats led to decreased concentrations of plasma fatty acids, phospholipids, triglycerides and total cholesterol as a function of dose. The decrease began at 0.1 mg.kg-1 and was highly significant at 3 mg.kg-1. In the same conditions, the intraperitoneal administration of Agr 529 caused a dose dependent hypolipemia. There was no apparent effect on cholesterol and on the triglycerides of high density lipoproteins. A kinetic study showed that the antilipemic effect of Agr 529 intravenously injected at 3 mg.kg-1 began 30 minutes after the injection with a maximum effect at 2 hours. The effect persisted up to 8 hours after injection. The present results show that the administration of Agr 529 and Agr 540 to normal animals causes hypolipemia (decrease in fatty acids, phospholipids, triglycerides and cholesterol) and restores induced hypertriglyceridemia. These effects may be attributed to an interaction of the molecules with A1 purinergic receptors of adipose tissue. PMID- 1509200 TI - Variable involvement of rat skeletal muscles in paraoxon-induced necrotizing myopathy. AB - We studied the incidence of paraoxon-induced myopathy in several rat skeletal muscles in relation to the morphometric properties and oxidative metabolism of their fibers. The necrosis was most pronounced in the predominantly oxidative rich fiber-composed diaphragm. The purely oxidative-rich masseter and soleus muscles were also severely affected. All 7 mixed muscles with oxidative-poor fiber predominance were far less involved. A high correlation between oxidative capacity and the extent of the muscle fiber necrosis was evidenced in mixed muscles. No relation was found between the muscle fiber diameter and the susceptibility to necrosis. We conclude that muscles predominantly composed of highly oxidative fiber types are more susceptible to organophosphate-induced necrotizing myopathy. Oxidative capacity alone is not the only factor, however, as the mixed diaphragm was more involved than the purely oxidative-rich masseter and soleus. Several features of the distinct fiber types could be responsible for the variable vulnerability. PMID- 1509201 TI - Dioxygenase and hydroperoxidase activities of rat brain cytosolic lipoxygenase. AB - Dioxygenase and hydroperoxidase activities of dialyzed rat brain cytosolic lipoxygenase were studied using linoleic acid as the substrate. The formation and utilization of linoleic acid hydroperoxide was monitored spectrophotometrically at 234 nm. Dioxygenase activity was dependent upon the concentration of linoleic acid and enzyme. The optimum assay conditions necessary for maximal dioxygenase activity included the 0.5 mM linoleic acid, cytosol (100 micrograms of protein) as the enzyme source and pH 7.4. All the classical inhibitors of lipoxygenase, nordihydroguaiaretic acid, phenidone and 5,8,11-eicosatriynoic acid significantly inhibited dioxygenase activity in a dose dependent manner. A significant hydroperoxidase activity was observed towards xenobiotic substrates viz. benzidine, guaiacol, tetramethylphenylenediamine, thiobenzamide in the presence of linoleic acid. NDGA at 1 microM concentration inhibited benzidine oxidation (2.45 nmol product formed/min/mg protein) by 75%, while Phenidone at 0.125 microM and ETI at 20 microM inhibited benzidine oxidation by 30% and 25%, respectively. PMID- 1509202 TI - Involvement of serotonergic mechanisms in the inhibitory effect of U-50,488H on glutamate-induced lethality in mice. AB - The present study showed the involvement of serotonergic mechanisms in the protective effect of U-50,488H, a selective agonist of kappa-opioid receptors, against glutamate-induced lethality in mice. U-50,488H (1-10 mg/kg, i.p.) protected mice to a significant extent against glutamate-induced lethality, in a dose-related manner. This protective effect was not observed in p chlorophenylalanine- or methysergide-treated mice. These results suggested that 5 HT in the brain may play an important role in the protective effect of U-50,488H against glutamate-induced lethality. PMID- 1509203 TI - Abnormalities of the autonomic nervous system of the duodenum in streptozotocin induced diabetic rats. AB - The changes in sensitivity of the rat duodenum to ATP were examined in preparations from control rats and from rats with streptozotocin (STZ)-induced diabetes. ATP was able to relax the duodenum of control animals in a concentration-dependent manner and this relaxation was significantly increased in STZ-diabetic rats. In preparations from diabetic rats, relaxation responses to ATP were greater than those of age-matched control groups. These results suggest that functional changes or degeneration of non-adrenergic, non-cholinergic nerves in the myenteric plexus may occur in STZ-diabetic rats, and that these alterations may result in the increased sensitivity of the relaxation of the duodenum to ATP. PMID- 1509204 TI - Effect of propentofylline on ischemia-induced loss of muscarinic cholinergic receptor binding in the gerbil hippocampus. AB - Super-delayed loss of muscarinic-1 (M1) receptors and the protective effect of propentofylline on these changes were examined in the gerbil hippocampus after transient ischemia with radioactive pirenzepine. M1 receptors were markedly decreased in the gerbil hippocampus 14 days after transient ischemia. Single administration of propentofylline (20 mg/kg, ip) just after transient ischemia almost completely prevented the ischemia-induced decrease in the number of M1 receptors, and had no effect in sham-operated controls. These findings suggest that one of the therapeutic efficacies of propentofylline is the result of the normalization of the dysfunction of the acetylcholine neuronal system in cerebrovascular disease. PMID- 1509205 TI - Administration of vanadyl sulfate by gavage does not normalize blood glucose levels in streptozotocin-induced diabetic rats. AB - Vanadyl sulfate trihydrate was given by gavage to streptozotocin-induced diabetic rats for 21 days at doses of 0, 25, 50, or 75 mg/kg/day. In marked contrast to the reduction in plasma glucose observed in diabetic animals given vanadyl sulfate via drinking water, diabetic rats given vanadyl by gavage were not characterized by normoglycemia. Similarly, in contrast to the normalizing effect of vanadyl in drinking water, vanadyl by gavage had only a minimal influence on diabetes associated hyperphagia and polydipsia. Despite the lack of marked effect of vanadyl by gavage on the above parameters, tissue vanadium accumulation in the gavaged rats was similar to that reported for rats given vanadium by drinking water. The present results (taken together with previous data) show that the administration of vanadium by gavage is not a viable alternative to the use of insulin in diabetes treatment. PMID- 1509206 TI - Potent inhibition of MAO mediated propranolol metabolism by dimethyl sulfoxide in Hep G2 cells. AB - This communication reports on the effects of dimethyl sulfoxide (DMSO) on the oxidative metabolism of propranolol by the homogenate of the human hepatoma cell line Hep G2. The formation of multiple metabolites was monitored in the absence and presence of 0.1 to 2.0% of DMSO. For the primary cytochrome P450-mediated pathways, ring oxidation was significantly reduced by 1.3 to 2.0% DMSO, whereas side-chain oxidation was not affected. A gradual inhibition of the oxidative deamination of N-desisopropylpropranolol to its glycol metabolite was seen with 20% inhibition at a DMSO concentration of 0.1% and a maximum 75% inhibition at a DMSO concentration of 0.7%. This highly selective inhibitory effect of DMSO on oxidative drug metabolism appears to be directed towards MAO type A. PMID- 1509207 TI - Morphological development of the rat fetal pancreas. AB - Rat fetal pancreata of days 12 to 19 of gestation and those of neonates were examined with light and electron microscopes. The pancreas arose from the primitive epithelium of the foregut as two primordia (dorsal and ventral pancreatic primordia) of epithelial cell nests surrounded with abundant fetal mesenchymal tissue between days 11 and 12. Primitive pancreatic islets, which mainly consisted of the endocrine cells with A cell type secretory granules, also appeared in the primordia at this age. The epithelial cell nests elongated gradually and had a branching cord-like arrangement. Two pancreatic primordia fused together on day 15, and an apparent ductular structure was observed on days 15 to 17. An acinar configuration of exocrine cells with zymogen granules gradually formed between days 17, 18 and 19. After birth, the volume of pancreatic parenchyma markedly increased and that of mesenchymal tissue prominently decreased. Ultrastructurally, the pancreatic primordia in the early stage showed immature epithelial features with the surrounding basement membrane and inconspicuous intercellular junctions. This might imply a plasticity in cellular differentiation of protodifferentiated pancreatic epithelial cells toward a ductular structure of immature exocrine pancreas which appeared later. In addition to the basement membrane, abundant fetal mesenchymal tissue was considered to play a possible role in the early morphogenesis in pancreatic development. PMID- 1509208 TI - Identification and quantitative analysis of urinary metabolites of dichloropropanols in rats. AB - Urinary metabolites of dichloropropanols in rats were analyzed by gas chromatography-mass spectrometry (GC/MS). Solutions of dichloropropanols consisting of 1, 3-dichloro-2-propanol (DC2P) and 2, 3-dichloro-1-propanol (DC1P) were diluted in a saline at the concentration of 100 mg/ml, and 0.1 ml of the solutions were subcutaneously injected into male Wistar rats weighing about 160g. The urine samples were collected over a period of 24 hours after the injections. DC2P and DC1P in the urine were extracted with ethylacetate and analyzed by a GC/MS. The derivatization procedure with 4-bromophenylboric acid after acetonitril extraction was applied for the analyses of diols in the urine. By the GC/MS analysis, 3-chloro-1, 2-propanediol (3CPD), 2-chloro-1, 3-propanediol (2CPD) and 1, 2-propanediol (PPD) were identified as the hydroxylated metabolites of dichlorpropanols. Based on the analytical results, the metabolic pathways of dichlorpropanols forming 3CPD and 2CPD, and then hydroxylating to PPD were elucidated. PMID- 1509209 TI - Cloning of the 5' flanking region of the murine laminin B1 gene by genomic PCR. AB - Induction of the murine laminin B1 gene in F9 cells occurs 24-48 hours after the retinoic acid (RA) addition. In order to reveal the mechanism of the late induction of the laminin B1 gene, it is necessary to understand fully the promoter structure of it. We report here that the promoter region of the laminin B1 was rapidly isolated utilizing the genomic PCR technique. MgCl2, formamide concentration, and annealing temperature were optimized for PCR. The result showed that MgCl2 concentration profoundly affects the efficiency in amplifying the specific DNA. The annealing temperature (51 degrees C-63 degrees C) did not significantly affect the yield. Under the optimal conditions, about 50 ng of the specific DNA was obtained from 1 microgram of total genomic DNA after 20 cycles of amplification, indicating that approximately 2 x 10(5) fold specific amplification had occurred. Southern blot analysis and sequence data proved that the amplified DNA fragment contained the promoter region of the laminin B1 gene. PMID- 1509210 TI - [Effects of ethylene oxide inhalation on mice]. AB - Male ddY mice were exposed to ethylene oxide (EO) at a concentration of 400 ppm, 6 hours a day, 3 days a week for 13 weeks and the effects of EO on the hepatic drug metabolizing enzymes were investigated. The liver and spleen weight per body weight did not change. Compared to the control group, the kidney weight of the exposed group increased while the testis weight decreased significantly. Hematological examination showed macrocytic anemia in the exposed group. Contents of microsomal cytochrome P-450 in the exposed group increased twice as much as that in the control group, while microsomal protein, cytochrome b5, protoheme and NADPH-cytochrome C reductase activity did not change. NADH-ferricyanide reductase activity of the exposed group increased significantly. Among the glutathione related enzymes in the liver, glutathione reductase and glutathione peroxidase activities in the exposed group decreased but glutathione-S-transferase activity increased significantly. PMID- 1509211 TI - [Thermal distribution in the agar phantom by a new intracavitary RF applicator for prostate gland]. AB - Some studies suggest that the prostate gland is one of the most difficult portions of the body to heat up even by radio frequency (RF) capacitive heating, which is well established as a useful means for deep regional hyperthermia because of its non-uniform power absorption. We have developed a new type of intracavitary applicator for RF capacitive heating which can be connected to an 8 MHz RF heating device (Thermotron-RF8). The applicator is a balloon-type catheter which is filled with electrolyte, such as physiological saline, 3% saline or 3% ferrous sulfate solution, and then put between a pair of regular RF capacitive heating electrodes. The heating characteristics of the applicator were examined by using an agar phantom that is electrically equivalent to muscles. When the applicator was connected to the electrode of the RF generator with a copper cord, the balloon filled with electrolyte operated as an inner electrode. The effective hot area around the balloon of the catheter was observed, and the size of the hot area was changed by the kinds of electrolytes used and their concentration. With this adaptive technique, it is possible to maintain an adequate thermal distribution at a tumor in the uterus, urinary bladder and rectum, as well as the prostate gland. PMID- 1509212 TI - [The suppression of CK activity in the brain by acrylamide]. AB - In vitro, both acrylamide and bis-acrylamide inhibited the activity of purified creatine kinase (CK) from the human brain with almost the same potency. The inhibition was dose-dependent and non-competitive. In vivo, however, only acrylamide caused the splay of hind limbs and an awkward gait in rats, and inhibited CK activity in the brain. The CK activity of the regions of the brain investigated differed, and these distributions were well matched with those of human cases. The inhibition became more marked as the administration of acrylamide was repeated. While the distribution of 14C in the different regions of the brain did not differ after the injection of [14C] acrylamide, the degree of the suppression of CK activity differed in these regions and was most marked in the hypothalamus. Fifty-two-week-old rats appeared more susceptible to acrylamide than 8-week-old rats. However, no difference in the inhibition of the CK activity in the brain was noted between the older and the young ones. The possible relation of the regional differences of CK suppression with the pathogenesis of acrylamide encephalopathy is discussed. PMID- 1509213 TI - [Fulminant hepatitis after the inhalation of dichloropropanols]. AB - A fatal case of acute fulminant hepatitis following exposure to dichloropropanols is reported. A 59-year-old male worker in a chemical plant developed general malaise, nausea and vomiting several hours after cleaning a tank that had contained dichloropropanols. He had no previous history of hepatic dysfunction. On admission, hepatomegaly was prominent. Because of highly elevated levels of GOT and GPT in the serum, reduced prothrombin time and a lowered consciousness level, a diagnosis of fulminant hepatitis was made. Significant decreases of leukocytes and platelets were also observed. Serum creatinine and BUN were slightly elevated. Although plasma exchanges were conducted on the third and fourth day, the liver functions continued to deteriorate. The patient died on the fifth day. Because dichloropropanols could be detected in the blood specimens obtained at the time of admission, we considered that fulminant hepatitis in this case was attributed to dichloropropanols exposure. To our knowledge, this is the first case of fulminant hepatitis after dichloropropanols-exposure. PMID- 1509214 TI - [Toxicity of dichloropropanols--changes in hematological findings and serum chemistry]. AB - We investigated the toxicity of dichloropropanols (DCPs) in hematological findings and serum chemistry. The solutions of two isomers of DCPs, 1,3-dichloro 2-propanol (DC2P) and 2,3-dichloro-1-propanol (DC1P) were dissolved in saline at the concentration of 100 mg/ml, and 0.1 ml of each solution was subcutaneously injected into male Wistar rats weighing about 200 g. At 6 hours after the injections, in the DC2P group, the number of white blood cells and platelets showed a significant decrease. Transaminases, alkaline phosphatase and lactate dehydrogenase were greatly elevated. Blood urea nitrogen and creatinine also showed a significant increase. There were no changes in the measurements in the DC1P group. These results indicate that there is a prominent hepatotoxicity in DC2P, and that there is a considerable difference in the toxicity present in DC2P and DC1P. Furthermore, in the workplace where DCPs, especially DC2P, is used, the monitoring of the working environment and biological monitoring should be mandatory. PMID- 1509215 TI - [Effects of methylmercury chloride on creatine kinase activity in the rat brain]. AB - The effects of methylmercury chloride (MMC) on creatine kinase (CK) activity in the rat brain were studied. Male Wistar rats were injected subcutaneously with 10 mg MMC/kg body weight/day for 7 consecutive days, and sacrificed on the 15th day when all rats showed a crossing phenomenon of the hind limbs. CK activity was mildly inhibited in the anterior, mid and posterior cerebral cortex. Aspartate aminotransferase and lactate dehydrogenase activities were also inhibited in some parts of the cerebral cortex, almost to the same extent as the CK activity. No definite inhibition of the enzyme activity was found in the striatum and the cerebellum. From this study we concluded that the mild inhibition of CK activity does not seem to play an important role in the genesis of neurotoxicity of MMC. PMID- 1509216 TI - Morphology of the normal visual field in a population-based random sample: principal components analysis. AB - I applied principal components analysis to Humphrey central 24-2 threshold values from both eyes of 304 clinically normal persons selected by simple random sample from Barbados, WI. The first component, accounting for 62 per cent of the variation, is equivalent to the average threshold value within persons. The first eigenvector, when represented by grey scale maps depicting a pair of eyes, reveals that, as average threshold increases, the visual field rises and flattens, like an umbrella that, initially closed, is simultaneously opened and thrust upwards. I verify three numerical predictions based upon this umbrella description. Much less important sources of variation involve disparity between fellow eyes, and hemimeridional and other symmetric differences within eyes. I discuss briefly possible physiologic explanatory mechanisms. PMID- 1509217 TI - Some large-sample distribution-free estimators and tests for multivariate partially incomplete data from two populations. AB - The most common instance of multivariate observations is the case of repeated measures over time. The two most widely used methods for the analysis of K repeated measures for two groups are the K degrees of freedom (d.f.) T2 MANOVA F test and the within-subjects 1 degree of freedom ANOVA F-test. Both require complete samples from normally distributed populations. In this paper, I describe alternative K and 1 d.f. distribution-free procedures which allow for randomly missing observations. These include a large-sample analysis of means, the Wei and Lachin multivariate Wilcoxon test with estimates of the Mann-Whitney parameter, and a multivariate Hodges-Lehmann location shift estimator based on the multivariate U-statistic of Wei and Johnson. Each of these methods provides a distribution-free K-variate estimate of the magnitude of group differences which can be used as the basis for an overall test of group differences. These tests include the K d.f. omnibus T2-like test, 1 d.f. tests of restricted hypotheses, such as the Wei-Lachin multivariate one-sided test of stochastic ordering, and the test of general association based on a minimum variance generalized least squares (GLS) estimate of the average group difference. I then describe covariate stratified-adjusted GLS estimates and tests of group differences. This approach also provides tests of homogeneity (interaction) for within-subjects and between subjects effects. I illustrate these analyses with an analysis of repeated cholesterol measurements in two groups of patients, stratified by sex. Such analyses provide an overall distribution-free summary estimate and test of the treatment effect obtained by combining the group differences over both time (repeated measures) and strata. PMID- 1509218 TI - A model for estimating level and net severity of spinal cord injuries. AB - Objective and detailed neurological assessments are essential in studies of the treatment and the epidemiology of acute spinal cord injuries. In practice, investigators use the expanded score, found by taking the total of the individual determinations, but this summary obscures important detail as to the level and the overall severity of injury. To address this issue, we present a method for estimating level and net severity of injury that makes use of isotonic regression and the Spearman-Karber estimator. We describe the method for both sensory and motor assessments of neurologic function. In the special case where one gives an identical weight to the response at each level, these estimators algebraically partition the expanded score into separate contributions due to level and net severity. We provide a numerical example using data from the first National Acute Spinal Cord Injury Study, and we present a summary of the distribution of these parameters for this population. PMID- 1509219 TI - Childhood blood pressure tracking correlations corrected for within-person variability. AB - The correlation coefficient between initial and subsequent blood pressure (BP) measurements is referred to as the tracking correlation. Childhood BP tracking correlations, although positive, have been considered too low to make accurate predictions for an individual. These correlations, however, can be raised substantially by averaging BP over multiple weekly visits in each year, which partially accounts for within-person variability. In a cohort of 333 school children, we measured BP 3 times on each of 4 successive weekly visits, in each of 4 consecutive years, using a random-zero sphygmomanometer. Approximately 90 per cent of subjects had data for one or more follow-up years, and 75 per cent of subjects who entered in the first year had data for all four years. With a model that allows estimation of correlations and that uses all available longitudinal data, we calculated tracking correlations completely corrected for within-person variability, the statistical equivalent of measuring BP on an infinite number (infinity) of visits and measurements per visit. Age-sex adjusted tracking correlations for 3 years of follow-up based on the means from 1,2,3,4, and infinity visits are, for systolic BP, 0.43, 0.56, 0.62, 0.66, and 0.73, respectively, and for diastolic BP, 0.20, 0.37, 0.46, 0.50, and 0.70, respectively. With longer follow-up, the use of corrected tracking correlations would allow determination of the maximal extent to which childhood BP can predict adult levels, and therefore the usefulness of screening to identify children at high risk of developing hypertension. PMID- 1509220 TI - Using follow-up data to avoid omitted variable bias: an application to cardiovascular epidemiology. AB - Omitted variable bias is discussed in the context of linear models. It is shown that the effect of omitted variables can be controlled in linear models for metric dependent variables by using data from follow-up studies. Two different models for analysing such data are proposed. In the first model the omitted variables are assumed to be uncorrelated with the explanatory variables in the model and to be constant over time. These assumptions lead to a special structure of the covariance matrix of the errors over time. Efficient estimation of the parameters in the linear model has to take this special covariance matrix of the errors into account by using appropriate generalized least squares or maximum likelihood methods. In the second model the omitted variables are assumed to be time constant. Additionally, they are allowed to be correlated with the explanatory variables, that is these variables are omitted confounders in the usual epidemiological sense. It is shown that even in this case the parameters of the linear model can be estimated consistently with ordinary least squares if a follow-up study is available. The differences between the parameter estimates under the first and the second model may be used to construct a Hausman test for misspecification. The models, the estimation methods and the Hausman test are illustrated by the example that explores the determinants of serum cholesterol in German adoloscents of both sexes. PMID- 1509221 TI - Divergent biases in ecologic and individual-level studies. AB - Several authors have shown that ecologic estimates can be biased by effect modification and misclassification in a different fashion from individual-level estimates. This paper reviews and discusses ecologic biases induced by model misspecification; confounding; non-additivity of exposure and covariate effects (effect modification); exposure misclassification; and non-comparable standardization. Ecologic estimates can be more sensitive to these sources of bias than individual-level estimates, primarily because ecologic estimates are based on extrapolations to an unobserved conditional (individual-level) distribution. Because of this sensitivity, one should not rely on a single regression model for an ecologic analysis. Valid ecologic estimates are most feasible when one can obtain accurate estimates of exposure and covariate means in regions with internal exposure homogeneity and mutual covariate comparability; thus, investigators should seek out such regions in the design and analysis of ecologic studies. PMID- 1509222 TI - Digit preference in estimated gestational age. AB - A digit preference model is developed to describe the preference for estimating gestational age at birth as an even week during the 20th to 36th week of gestation. The model incorporates a probability of misclassification to adjacent even weeks at odd gestational ages, while even gestational ages are assumed correctly classified. The model is extended to allow the misclassification probabilities to decrease linearly with week during the period. A piecewise exponential model is used to model relative risks of delivery associated with a previous spontaneous abortion and a model incorporating digit preference is fitted as a generalized bilinear model in GLIM. The estimates of relative risk in the underlying survival model are virtually the same whether the misclassification is incorporated in the model or ignored. PMID- 1509223 TI - Power and sample size evaluation for the McNemar test with application to matched case-control studies. AB - Various expressions have appeared for sample size calculation based on the power function of McNemar's test for paired or matched proportions, especially with reference to a matched case-control study. These differ principally with respect to the expression for the variance of the statistic under the alternative hypothesis. In addition to the conditional power function, I identify and compare four distinct unconditional expressions. I show that the unconditional calculation of Schlesselman for the matched case-control study can be expressed as a first-order unconditional calculation as described by Miettinen. Corrections to Schlesselman's unconditional expression presented by Fleiss and Levin and by Dupont, which use different models to describe exposure association among matched cases and controls, are also equivalent to a first-order unconditional calculation. I present a simplification of these corrections that directly provides the underlying table of cell probabilities, from which one can perform any of the alternative sample size calculations. Also, I compare the four unconditional sample size expressions relative to the exact power function. The conclusion is that Miettinen's first-order expression tends to underestimate sample size, while his second-order expression is usually fairly accurate, though possibly slightly anti-conservative. A multinomial-based expression presented by Connor, among others, is also fairly accurate and is usually slightly conservative. Finally, a local unconditional expression of Mitra, among others, tends to be excessively conservative. PMID- 1509224 TI - Falsificationism and clinical trials. PMID- 1509226 TI - Applied physiology of amateur wrestling. AB - The general physiological profile of the successful wrestler is of one having high anaerobic power (mean range of 6.1 to 7.5 W/kg for arms; mean range of 11.5 to 19.9 W/kg for legs); high anaerobic capacity (range for arms 4.8 to 5.2 W/kg; range for legs 7.4 to 8.2 W/kg); high muscular endurance; average to above average aerobic power (range 52 to 63 ml/kg/min); average pulmonary function (range 1.90 to 2.02 L/kg/min for VEmax); normal flexibility; a high degree of leanness (range 3.7 to 13.0% fat) excluding heavyweights; and a somatotype that emphasises mesomorphy. Training methods include wrestling, and nonwrestling activities for increasing strength and power (i.e. resistance training), and to improve cardiovascular fitness (i.e. endurance training). Unfortunately, data on the isolated effects of wrestling on fitness and the type of training programme most effective for success in wrestling are scarce. The practice of weight loss is commonly used by wrestlers to enhance performance. Rapid weight loss has profound adverse effects on the wrestler's physiology but little effect on strength or anaerobic power performance as measured in the laboratory. In contrast, muscular endurance appears to be impaired by the rapid weight loss. Current research on weight loss and performance in wrestlers has taken 2 directions: (a) towards nutritional treatments to prevent suboptimal muscular endurance, and (b) towards the development of programmes to estimate minimal weight based on body composition techniques and thereby prevent weight reductions. PMID- 1509227 TI - Iliotibial band syndrome. AB - The iliotibial band syndrome is most often diagnosed in runners but can be found in athletes who participate in other sports. From our experience most patients are high mileage runners with shoes either worn out or with insufficient cushioning. A total of 19 athletes with this condition have been seen in the past 3 years. Treatment consisted of rest or decreased distance, shoe changes, modification in exercise technique, anti-inflammatory medication, steroid injections and stretching. Surgery was not required. PMID- 1509225 TI - Neuromuscular electrical stimulation and voluntary exercise. AB - Neuromuscular electrical stimulation (NMES) has been in practice since the eighteenth century for the treatment of paralysed patients and the prevention and/or restoration of muscle function after injuries, before patients are capable of voluntary exercise training. More recently NMES has been used as a modality of strengthening in healthy subjects and highly trained athletes, but it is not clear whether NMES is a substitute for, or a complement to, voluntary exercise training. Moreover the discussion of the mechanisms which underly the specific effects of NMES appears rather complex at least in part because of the disparity in training protocols, electrical stimulation regimens and testing procedures that are used in the various studies. It appears from this review of the literature that in physical therapy, NMES effectively retards muscle wasting during denervation or immobilisation and optimises recovery of muscle strength during rehabilitation. It is also effective in athletes with injured, painful limbs, since NMES contributes to a shortened rehabilitation time and aids a safe return to competition. In healthy muscles, NMES appears to be a complement to voluntary training because it specifically induces the activity of large motor units which are more difficult to activate during voluntary contraction. However, there is a consensus that the force increases induced by NMES are similar to, but not greater than, those induced by voluntary training. The rationale for the complementarity between NMES and voluntary exercise is that in voluntary contractions motor units are recruited in order, from smaller fatigue resistant (type I) units to larger quickly fatiguable (type II) units, whereas in NMES the sequence appears to be reversed. As a training modality NMES is, in nonextreme situations such as muscle denervation, not a substitute for, but a complement of, voluntary exercise of disused and healthy muscles. PMID- 1509230 TI - Some concepts and principles of clinical test evaluation. Classification, analytical performance, monitoring and clinical interpretation. Working Group for the Nordic Clinical Chemistry Project (NORDKEM). PMID- 1509228 TI - Knee extensor performance in runners. Differences between specific athletes and implications for injury prevention. PMID- 1509229 TI - Incidence, severity, aetiology and prevention of sports injuries. A review of concepts. AB - Notwithstanding the healthy influence of sporting activities on risk factors, in particular those of cardiovascular disease, it is becoming increasingly apparent that sports can present a danger to health in the form of sports injuries. The extent of the sports injury problem calls for preventative action based on the results of epidemiological research. For the interpretation of these facts uniform definitions are needed and limitations of research designs should be known. Measures to prevent sports injuries form part of what is called the 'sequence of prevention'. Firstly the extent of the sports injury problem must be identified and described. Secondly the factors and mechanisms which play a part in the occurrence of sports injuries have to be identified. The third step is to introduce measures that are likely to reduce the future risk and/or severity of sports injuries. This measure should be based on the aetiological factors and the mechanism as identified in the second step. Finally the effect of the measures must be evaluated by repeating the first step. In this review some aspects of the first and second step of the sequence of prevention are discussed. The extent of the sports injury problem is often described by injury incidence and by indicators of the severity of sports injuries. Sports injury incidence should preferably be expressed as the number of sports injuries per exposure time (e.g. per 1000 hours of sports participation) in order to facilitate the comparability of research results. However, one should realise that the outcome of research applying this definition of sports injury incidence is highly dependent on the definitions of 'sports injury' and 'sports participation'. The outcome of such research also depends on the applied research design and research methodology. The incidence of sports injuries depends on: the method used to count injuries (e.g. prospective vs retrospective); the method used to establish the population at risk; and on the representativeness of the sample. Severity of sports injuries can be described on the basis of 6 criteria: the nature of the sports injury; the duration and nature of treatment; sporting time lost; working time lost; permanent damage; and cost. Here also uniform definitions are important and necessary in order to enhance the comparability of research data. In the second step of the 'sequence of prevention' the aetiological factors that play a role in the occurrence of a sports injury have to be identified by epidemiological studies. Epidemiological research on the aetiology of sports injuries requires a conceptual model.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1509231 TI - Neurocysticercosis: a short review and presentation of a Scandinavian case. AB - Cysticercosis is a disease entity caused by the larval form (Cysticercus cellulosae) of the pork tapeworm (Taenia solium). When man becomes the intermediate host, cysticercal cysts can develop in various organs. Neurocysticercosis, i.e. cysticercosis of the central nervous system, can lead to a broad range of neurological disturbances. The disease is usually confined to geographical regions where sanitation is poor but can occur among immigrants or travellers from such regions. Due to increased travel and immigration the disease may appear in non-endemic areas. We describe a recent case of neurocysticercosis in a 28-year-old Danish woman, who had been travelling in the Far East. She was successfully treated with praziquantel. A short review of the literature is given as the knowledge of the diagnosis and treatment of the disease has increased greatly in the last decade. PMID- 1509232 TI - Polymerase chain reaction with double primer pairs for detection of human parvovirus B19 induced aplastic crises in family outbreaks. AB - Parvovirus B19 DNA can be detected by polymerase chain reaction with double primer pairs (nested PCR). Recent infection was documented by a retrospective serological study using Parvoscan-B19 enzyme linked immunosorbent assay (EIA) for detection of B19 human parvovirus IgM and IgG antibodies in serum or plasma specimens. In 3 families B19 outbreaks caused aplastic crises necessitating blood transfusion in 5 children and 1 adult with hereditary sphaerocytosis. Four members from 2 of the families had clinically overt haemolytic anaemia prior to the event. Two members in another family presented with an aplastic crisis disclosing the underlying chronic haemolytic disease. All 7 patients were identified as PCR positive in serum samples taken 3-14 days after the onset of symptoms. Comparison with dot blot hybridization revealed detectable DNA in only 2/3 PCR positive patients. Thus, nested PCR is more sensitive than the dot blot hybridization method and is therefore a suitable complement to the antibody assay for identifying recent B19 infection. PMID- 1509233 TI - Impact of the 1987 revised AIDS case definition in Denmark: a follow-up study 2 years after its adoption. AB - We present a follow-up study on Danish AIDS patients notified according to the latest revision of the AIDS case definition during the first 2 years after its adoption. A total of 271 adult AIDS cases were notified in the period of study (Jan. 1, 1988-Dec. 31, 1989). 60 patients (22%) met only the revised AIDS case definition and of these 17 patients (28%) developed diseases meeting the old AIDS case definition. Thus, AIDS reporting increased by 28% due to the change in case definition, the impact being 19% after adjusting for patients developing old case diseases. No time trend in the impact was found. We estimated the cumulative percent of cases meeting the new case definition who subsequently will develop diseases meeting the old definition as 15% after 6 months and 51% after 18 months. The revision produced a disproportionate increase in reporting of female cases (p less than 0.05), transfusion cases (p less than 0.01) and to a lesser extent of heterosexual cases, while the impact on reporting of homo/bisexual men showed a decrease (p less than 0.01). Cases notified with new case definition diseases were older than cases notified with old diseases. Among patients meeting only the new case definition, 25 died and 18 (30%) had not developed old case diseases before death. We found no difference in survival rates between patients within the 2 groups of case definition. Among patients meeting the new definition we found no differences in HIV antigenemia or CD4 cell count between those developing diseases meeting old case definition and those who did not. PMID- 1509234 TI - Pneumocystis carinii pneumonia in AIDS patients: clinical course in relation to the parasite number found in routine specimens obtained by fiberoptic bronchoscopy. AB - The aim of this study was to evaluate whether the amount of Pneumocystis carinii organisms found at fiberoptic bronchoscopy (FB) performed on HIV-positive patients correlated to the character of the P. carinii pneumonia (PCP). A consecutive series of 105 patients presented with 131 episodes of pulmonary symptoms requiring FB, and in 75 of these episodes a diagnosis of PCP was made. Specimens were stained with Giemsa and methenamine silver nitrate and the number of parasites found was given as: numerous, many, few or none. The following signs and symptoms were registered: cough, dyspnoea, fever, loss of weight, chest radiograph, haemoglobin, WBC, CD4 cell count, PO2 and HIV p24 antigen. The PCP was characterized by the clinical course: mild, moderate, severe, and by the outcome: pulmonary healthy, pulmonary insufficiency and death. No correlations between the number of P. carinii organisms and the clinical course or outcome of the PCP, the symptoms before the FB or the paraclinical examinations were found. In conclusion, the routinely obtained quantitative results of the microbiological examinations of material from the lungs were not correlated to the severity of the PCP. PMID- 1509235 TI - Serum carcinoembryonic antigen: a prognostic marker in HIV-related Pneumocystis carinii pneumonia. AB - Serum concentrations of carcinoembryonic antigen (CEA) were measured in 43 consecutive patients with HIV-related Pneumocystis carinii pneumonia (PCP). The subjects were divided into 2 groups according to the severity of the PCP:PaO2 in ambient air (AA) less than or equal to 50 mmHg on admission (n = 22, group 1) and PaO2 greater than 50 mmHg (n = 21, group 2). In addition, 57 HIV patients with either non-PCP pulmonary diseases (n = 34, group 3) or extrapulmonary disease (n = 23, group 4) were studied. Mean CEA levels (ng/ml) were 13 +/- 10 in group 1 and 4.9 +/- 5.5 in group 2 (p less than 0.001). The corresponding values in groups 3 and 4 were much lower (2.7 +/- 1.8 and 2.4 +/- 1.8, respectively). In group 1, mean initial CEA levels were higher (p less than 0.001) in the patients who died (n = 6; 23.5 +/- 11) than in the survivors (n = 16; 8.9 +/- 7), although the initial mean PaO2 were identical (39 +/- 7 and 39 +/- 8 mmHg, respectively) and the initial mean LDH levels were not significantly different (1544 +/- 530 and 1200 +/- 457 IU/l). CEA levels fell during specific anti-PCP therapy associated with corticosteroids but returned to normal only in the survivors. We conclude that CEA levels are increased in patients with PCP and acute respiratory distress. Among the patients with PaO2 levels of less than or equal to 50 mmHg before treatment, only high levels of CEA (greater than 20 ng/ml) were associated with a fatal outcome, regardless of anti-PCP therapy associated with corticosteroids.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1509236 TI - Isolation of genital mycoplasmas from blood of febrile obstetrical-gynecologic patients and neonates. AB - In a prospective study, 1156 blood specimens collected from hospitalized febrile obstetrical-gynecologic patients and neonates with suspected sepsis, were inoculated into a conventional biphasic culture medium, Castaneda S and cultures incubated aerobically. 15-24 h later the broth cultures were subcultured to specific media for detection of mycoplasmas. Genital mycoplasmas were isolated in 15 samples (taken from 8 women) and in 2 from 1 neonate. Mycoplasmas and members of the family Enterobacteriaceae were the most frequent significant bacteria isolated from adult specimens. Mycoplasma isolations were associated with either postpartum or postabortum febrile infections in women. Four of the neonates, whose mothers were infected, showed respiratory distress at birth; 1 of them had mycoplasmas in the blood. All febrile states in obstetrical or gynecological patients, and in neonates, should routinely lead to blood cultures for detection of mycoplasmas and ureaplasmas. PMID- 1509237 TI - Incidence, serogroups and case-fatality rate of invasive meningococcal infections in a Swedish region 1975-1989. AB - In a retrospective study of invasive meningococcal infections in Greater Gothenburg, Sweden, 213 cases of culture-verified meningitis or septicaemia were identified during the 15-year period 1975-1989. The annual incidence was 2.0/100,000. Cases were seen in all age-groups with the highest rates in the 0-4 and 15-19 year-old groups, 9.5 and 6.2/100,000 respectively. 20% of the patients were less than 2 years. 91% of the patients had no known risk factors. In only 10 cases (5%) was contact with another case of meningococcal infection known. The main clinical manifestations were meningitis (57%), septicaemia with no sign of focal infection (25%) and septic shock (17%). The case-fatality rate for all the patients was 6.6% and did not change during the 15-year period. One-third of the patients who presented with septic shock died. The serogroup was known for strains from 192 patients. 51% of the strains belonged to serogroup B, 10% to group A and 23% to group C. In conclusion, the incidence of meningococcal infection was low but the relatively high case-fatality rate warrants a search for effective prophylaxis. About 30% of the cases were potentially preventable by the currently available tetravalent (A, C, Y and W135) polysaccharide vaccine, which is immunogenic in children greater than 2 years. Widespread use of antibiotic prophylaxis to close contacts of known cases would not lower the incidence markedly. PMID- 1509238 TI - Amplification of DNA by the polymerase chain reaction for the efficient diagnosis of pertussis. AB - The standard diagnostic methods for pertussis have several shortcomings. With the increased knowledge of the Bordetella pertussis genome a specific and conserved DNA sequence, present in about 70-80 copies in each genome, was selected for amplification with the polymerase chain reaction (PCR) technique in order to evaluate its diagnostic potential in children with suspected pertussis. The 400 basepair DNA sequence chosen was present and amplified in all 112 B. pertussis strains and in no other bacterial species examined. The specificity of the amplified material was documented by restriction enzyme cleavage. In nasopharyngeal aspirates a B. pertussis specific PCR product was visualized in 19/25 culture positive and in 5/50 culture negative children. In conclusion the present PCR assay for B. pertussis can be clinically useful and permit a specific diagnosis within 1 day after sampling. Further studies are requested to document its sensitivity, specificity and predictive value for positive and negative results. PMID- 1509240 TI - Septic complications to sphenoidal sinus infection. AB - Sphenoid sinusitis is an uncommon infection, but an early diagnosis and appropriate treatment is important because of its serious complications. We report 4 patients (28, 28, 37 and 28 years old) admitted to a department of infectious diseases with meningitis, sepsis and orbital cellulitis as complications of acute sphenoidal cavity infection. The cases illustrate the value of computed tomography (CT) scan of the sphenoid sinus in the evaluation of patients with clinical features suspicious of sphenoid sinusitis. PMID- 1509239 TI - The relative importance of Shigella in the aetiology of childhood gastroenteritis in Saudi Arabia. AB - The role of shigella infection in childhood gastroenteritis was studied over a 2 year period. Shigella species were found in the faecal specimens of 70 (1%) of 7369 children with gastroenteritis, but in only 1 (0.1%) of 1130 controls. S. flexneri was the commonest isolate (51%), followed by S. sonnei (37%). Most shigella species were isolated during the winter. The prevalence of shigellosis was highest for children 1-5 years of age but equal for both sexes. Fever, abdominal cramps, vomiting, and bloody diarrhoea were the predominant clinical features. Of the shigella isolates, 73% were resistant to cotrimoxazole, 43% to ampicillin, and 41% to chloramphenicol. One-third of isolates were resistant to greater than or equal to 3 antibiotics. All isolates were susceptible to nalidixic acid. The illness was mild and self-limiting and most patients recovered without antimicrobial therapy. PMID- 1509241 TI - Septicemia in granulocytopenic patients: a shift in bacterial etiology. AB - 35 episodes of septicemia in 33 patients occurred among 269 consecutive patients with granulocytopenia (granulocyte cell count less than or equal to 0.5 x 10(9)/l) during the 7-year period 1982-1988. 59% of isolated bacteria were Gram positive (Staphylococcus aureus, Staph. epidermidis, Streptococcus species and Pneumococcus) and 41% Gram-negative (Pseudomonas aeruginosa, Escherichia coli, Klebsiella pneumoniae, Enterobacter, Acinetobacter and Citrobacter). Compared to the 7-year period 1975-1981, there was a decrease in the relative number of patients with Gram-negative septicemia. Thus, a shift from a predominating Gram negative etiology in the 1975-1981 period to a predominating Gram-positive etiology in the 1982-1988 period was noted. In both periods the mortality rate was high in patients with Gram-negative septicemia, especially in patients with a Ps, aeruginosa infection. PMID- 1509242 TI - Endotoxin, TNF-alpha, interleukin-6 and parameters of the cellular immune system in patients with intraabdominal sepsis. AB - The correlation of endotoxin (ET), tumor necrosis factor alpha (TNF-alpha), interleukin-6 (IL-6), and cellular immune parameters with multiple organ failure and lethal outcome in intraabdominal infections was studied in a group of 18 patients with peritonitis, abscess or pancreatitis. Of these patients, 7 developed respiratory failure and 5 died due to multiple septic organ failure. The peak levels of ET (2.7 +/- 1.3 ng/ml) in the course of the disease were followed by moderate increases of TNF-alpha (mean 147 +/- 41 pg/ml) and IL-6 (170 +/- 61 pg/ml) within 2 days. Analysis of the parameters for the last 12 days prior to death or discharge showed, that the patient group with lethal outcome was characterized by significant lower mean plasma levels of TNF-alpha (less than 75 pg/ml versus greater than 160 pg/ml) and IL-6 (less than 130 pg/ml versus greater than 270 pg/ml), as well as high rates of unstimulated thymidine uptake into peripheral mononuclear blood cells (greater than 44000 cpm/8 x 10(6) PMBC/18 h versus less than 24000 cmp), T-lymphocyte depression (CD3; approximately greater than 40% reduction) with lower T-helper/inducer subset cell numbers (mean CD:CD8 ratio 1.0 +/- 0.55 versus 1.8 +/- 0.2) and lower lectin (PHA) stimulation values (1.9 +/- 1.4 versus 4.1 +/- 1.0). These data demonstrate an anergic immune status with low mediator levels and depressed T-lymphocyte function in patients with poor prognosis.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1509244 TI - Intrauterine fetal death due to echovirus 11. AB - In a case of intrauterine fetal death in the 29th week of gestation, echovirus 11 could be isolated from the umbilical cord of the fetus. The mother had no apparent signs of infection but serological evidence of current echovirus 11 infection. Enterovirus PCR performed on paraffin-embedded specimens of various tissues (myocardium, lung, liver and placenta) from the fetus yielded positive results in all cases. These findings, together with supporting serological and epidemiological findings--e.g. proven echovirus 11 infection 3 weeks before in the 18-month-old son of the woman--constituted strong evidence that echovirus 11 infection was responsible for the fetal death. PMID- 1509243 TI - Child health in arid areas of Ethiopia: longitudinal study of the morbidity in infectious diseases. AB - We describe the incidence of some childhood infections in drought prone areas of southern Ethiopia. Our results are based on 24 months' biweekly observations of 828 children aged 0-5 years in the pastoralist community of Dubluk and the agricultural community of Elka. An average of 23% of the children in Dubluk and 13% in Elka were sick during any 2-week period. Diarrhoeal diseases represented the main cause of morbidity, but the yearly number of diarrhoeal episodes were lower than previously reported from Ethiopia. Respiratory tract infections and to a lesser extent diarrhoeal diseases, showed highest incidence rates during the main dry season. The highest incidence of lower respiratory tract infections coincided with an outbreak of measles. In Dubluk, children who lived near to the wells had higher incidence rates than those who lived further away, probably reflecting the importance of crowding on transmission rates. In Elka, literacy of mothers was associated with reduced incidence of both diarrhoeal and respiratory tract infections, whereas the use of open pit latrines was associated with increased diarrhoeal incidence. The decline in disease incidence in this region during the last months of our study may reflect an improvement of nutritional status. PMID- 1509245 TI - Hilar lymphadenopathy associated with Chlamydia pneumoniae infection. AB - A 27-year-old man with an acute Chlamydia pneumoniae infection and hilar lymph node involvement is reported. Further investigation gave no evidence of sarcoidosis or other known cause of enlarged hilar nodes. Serological tests proved an acute infection with C. pneumoniae Thus, an infection with C. pneumoniae may lead to enlargement of the hilar lymph nodes, and infection with this microorganism should be included in the differential diagnostic considerations in patients with hilar lymphadenopathy. PMID- 1509246 TI - Disseminated fungal disease resistant to fluconazole treatment in a child with leukemia. AB - During a chemotherapy induced leukopenic period fluconazole (3 mg/kg/day i.v.) was administered as empiric antifungal treatment in a 5-year-old girl with leukemia and a presumed catheter infection due to Staphylococcus epidermidis. Despite intensive treatment with antibiotics and fluconazole the patient died. In one blood culture Candida krusei was isolated post mortem, and at autopsy Aspergillus fumigatus was found in multiple organs. Both fungi showed high MIC values to fluconazole. We feel that this drug should not be used when the possibility of a systemic infection with an unidentified fungus exists. PMID- 1509247 TI - [Phytotoxicity studies on wild herbs and a cultured plant. Applicability of the ChemG related phytotoxicity test on wild herbs]. PMID- 1509248 TI - The microbial wars. PMID- 1509249 TI - AIDS and the polio vaccine. PMID- 1509250 TI - Liability bill introduced in Congress. PMID- 1509251 TI - Massey seeks to broaden NSF's role. PMID- 1509252 TI - Exploring new strategies to fight drug-resistant microbes. PMID- 1509253 TI - Genetic basis found for resistance to TB drug. PMID- 1509254 TI - Knockout mice offer first animal model for CF. PMID- 1509255 TI - Epidemiology of drug resistance: implications for a post-antimicrobial era. AB - In the last several years, the frequency and spectrum of antimicrobial-resistant infections have increased in both the hospital and the community. Certain infections that are essentially untreatable have begun to occur as epidemics both in the developing world and in institutional settings in the United States. The increasing frequency of drug resistance has been attributed to combinations of microbial characteristics, selective pressures of antimicrobial use, and societal and technologic changes that enhance the transmission of drug-resistant organisms. Antimicrobial resistance is resulting in increased morbidity, mortality, and health-care costs. Prevention and control of these infections will require new antimicrobial agents, prudent use of existing agents, new vaccines, and enhanced public health efforts to reduce transmission. PMID- 1509256 TI - Tuberculosis: commentary on a reemergent killer. AB - Tuberculosis remains the leading cause of death in the world from a single infectious disease, although there is little knowledge of the mechanisms of its pathogenesis and protection from it. After a century of decline in the United States, tuberculosis is increasing, and strains resistant to multiple antibiotics have emerged. This excess of cases is attributable to changes in the social structure in cities, the human immunodeficiency virus epidemic, and a failure in certain major cities to improve public treatment programs. The economic costs of not adequately addressing the problem of tuberculosis in this country are estimated from an epidemiological model. PMID- 1509257 TI - The crisis in antibiotic resistance. AB - The synthesis of large numbers of antibiotics over the past three decades has caused complacency about the threat of bacterial resistance. Bacteria have become resistant to antimicrobial agents as a result of chromosomal changes or the exchange of the exchange of genetic material via plasmids and transposons. Streptococcus pneumoniae, Streptococcus pyogenes, and staphylococci, organisms that cause respiratory and cutaneous infections, and members of the Enterobacteriaceae and Pseudomonas families, organisms that cause diarrhea, urinary infection, and sepsis, are now resistant to virtually all of the older antibiotics. The extensive use of antibiotics in the community and hospitals has fueled this crisis. Mechanisms such as antibiotic control programs, better hygiene, and synthesis of agents with improved antimicrobial activity need to be adopted in order to limit bacterial resistance. PMID- 1509258 TI - The origin of plagues: old and new. AB - Viruses and bacteria emerge in new and old forms to cause disease epidemics. Some microorganisms recur when changing life-styles (including increased international travel) offer new opportunities; others arise from new genetic variations. These various epidemics connect the future with the past, offering lessons for guarding the health of generations to come--lessons learned from diseases such as tuberculosis, toxic shock syndrome, Lyme disease, streptococcal infection, influenza, and acquired immunodeficiency syndrome (AIDS). The public must be vigilant to the possibility of new epidemics, learn more about the biology and epidemiology of microbes, and strengthen systems of surveillance and detection. PMID- 1509259 TI - Structure-based strategies for drug design and discovery. AB - Most drugs have been discovered in random screens or by exploiting information about macromolecular receptors. One source of this information is in the structures of critical proteins and nucleic acids. The structure-based approach to design couples this information with specialized computer programs to propose novel enzyme inhibitors and other therapeutic agents. Iterated design cycles have produced compounds now in clinical trials. The combination of molecular structure determination and computation is emerging as an important tool for drug development. These ideas will be applied to acquired immunodeficiency syndrome (AIDS) and bacterial drug resistance. PMID- 1509260 TI - Human and Drosophila homeodomain proteins that enhance the DNA-binding activity of serum response factor. AB - Cells with distinct developmental histories can respond differentially to identical signals, suggesting that signals are interpreted in a fashion that reflects a cell's identity. How this might occur is suggested by the observation that proteins of the homeodomain family, including a newly identified human protein, enhance the DNA-binding activity of serum response factor, a protein required for the induction of genes by growth and differentiation factors. Interaction with proteins of the serum response factor family may allow homeodomain proteins to specify the transcriptional response to inductive signals. Moreover, because the ability to enhance the binding of serum response factor to DNA residues within the homeodomain but is independent of homeodomain DNA-binding activity, this additional activity of the homeodomain may account for some of specificity of action of homeodomain proteins in development. PMID- 1509261 TI - Trefoil knotting revealed by molecular dynamics simulations of supercoiled DNA. AB - Computer simulations of the supercoiling of DNA, largely limited to stochastic search techniques, can offer important information to complement analytical models and experimental data. Through association of an energy function, minimum energy supercoiled conformations, fluctuations about these states, and interconversions among forms may be sought. In theory, the observation of such large-scale conformational changes is possible, but modeling and numerical considerations limit the picture obtained in practice. A new computational approach is reported that combines an idealized elastic energy model, a compact B spline representation of circular duplex DNA, and deterministic minimization and molecular dynamics algorithms. A trefoil knotting result, made possible by a large time-step dynamics scheme, is described. The simulated strand passage supports and details a supercoiled-directed knotting mechanism. This process may be associated with collective bending and twisting motions involved in supercoiling propagation and interwound branching. The results also demonstrate the potential effectiveness of the Langevin/implicit-Euler dynamics scheme for studying biomolecular folding and reactions over biologically interesting time scales. PMID- 1509262 TI - A mutation in the POU-homeodomain of Pit-1 responsible for combined pituitary hormone deficiency. AB - Pit-1 is a pituitary-specific transcription factor responsible for pituitary development and hormone expression in mammals. Mutations in the gene encoding Pit 1 have been found in two dwarf mouse strains displaying hypoplasia of growth hormone, prolactin, and thyroid-stimulating, hormone-secreting cell types in the anterior pituitary. A point mutation in this gene was identified on one allele in a patient with combined pituitary hormone deficiency. Mutant Pit-1 binds DNA normally but acts as a dominant inhibitor of Pit-1 action in the pituitary. PMID- 1509263 TI - Mutation of the POU-specific domain of Pit-1 and hypopituitarism without pituitary hypoplasia. AB - A point mutation in the POU-specific portion of the human gene that encodes the tissue-specific POU-domain transcription factor, Pit-1, results in hypopituitarism, with deficiencies of growth hormone, prolactin, and thyroid stimulating hormone. In two unrelated Dutch families, a mutation in Pit-1 that altered an alanine in the first putative alpha helix of the POU-specific domain to proline was observed. This mutation generated a protein capable of binding to DNA response elements but unable to effectively activate its known target genes, growth hormone and prolactin. The phenotype of the affected individuals suggests that the mutant Pit-1 protein is competent to initiate other programs of gene activation required for normal proliferation of somatotrope, lactotrope, and thyrotrope cell types. Thus, a mutation in the POU-specific domain of Pit-1 has a selective effect on a subset of Pit-1 target genes. PMID- 1509264 TI - The mouse pink-eyed dilution gene: association with human Prader-Willi and Angelman syndromes. AB - Complementary DNA clones from the pink-eyed dilution (p) locus of mouse chromosome 7 were isolated from murine melanoma and melanocyte libraries. The transcript from this gene is missing or altered in six independent mutant alleles of the p locus, suggesting that disruption of this gene results in the hypopigmentation phenotype that defines mutant p alleles. Characterization of the human homolog revealed that it is localized to human chromosome 15 at q11.2-q12, a region associated with Prader-Willi and Angelman syndromes, suggesting that altered expression of this gene may be responsible for the hypopigmentation phenotype exhibited by certain individuals with these disorders. PMID- 1509265 TI - Transactivation by AP-1 is a molecular target of T cell clonal anergy. AB - Anergy is a mechanism of T lymphocyte tolerance induced by antigen receptor stimulation in the absence of co-stimulation. Anergic T cells were shown to have a defect in antigen-induced transcription of the interleukin-2 gene. Analysis of the promoter indicated that the transcription factor AP-1 and its corresponding cis element were specifically down-regulated. Exposure of anergic T cells to interleukin-2 restored both antigen responsiveness and activity of the AP-1 element. PMID- 1509266 TI - Plakoglobin and beta-catenin: distinct but closely related. PMID- 1509267 TI - [Percutaneous drainage in renal emphysema. Clinical case]. AB - Renal emphysema is a rare and severe infection, that constitutes two clinical entities: emphysematous pyelonephritis and emphysematous pyelitis. We report a case in which the gas is localized both in the collecting system and in the parenchyma of the kidney. In our experience the percutaneous renal drainage has revealed to be able to dominate the infection but not to preserve renal function. PMID- 1509268 TI - Transperineal vesiculodeferentography under ultrasound control: first experiences. AB - Vesiculodeferentography (VDG) plays an important role in diagnosing male infertility and staging of prostatic cancer; the techniques of performing the examination are, today, well codified: 1) retrograde, by endoscopic cannulation of ejaculatory ducts; 2) anterograde, by cannulation of the deferent duct surgically prepared at the scrotum. In order to avoid the difficulties of the first method and the risks in the second (like stenosis and fibrosis of the deferent duct) we propose a new simple and safe method based on the direct transperineal puncture of the seminal vesicle under direct echographic control with a transrectal probe. We have studied 16 patients, mainly in order to stage prostatic cancer; the procedure was easy to perform, well tolerated and without consequences at seminal level. It required only 30 minutes, without anaesthesia and with a very low cost. The method permits a clear visualisation of anatomical structures and of possible pathologies with particular reference to vesicular invasion by a prostatic cancer. PMID- 1509269 TI - [Involvement of the urogenital system in HIV virus infection]. AB - Despite the genitourinary system is prone to infections by the Human Virus of Immunodeficiency, so far poor interest has been focused on urological manifestations of AIDS. We thoroughly reviewed the Literature and examined the different patterns of HIV infections on the kidneys, the prostate and the testes. An extensive description is given. PMID- 1509270 TI - [Pre-peritoneal trans-ileal uretero-cutaneostomy. Apropos of 41 cases]. AB - In the last 15 years we have used a modified version of the classic Bricker for external urine derivation in 41 cases (32 cases of neurobladder and 9 cancer of the bladder). This modification essentially involves placing the ileal loop in front of the peritoneum, in a superficial position which facilitates urethroileal anastomosis especially when trying to prevent reflux. The positioning of the loop greatly reduces urine stasis and ureteral stenosis, which in the classic Bricker is due to the ureter crossing the meso. We hope this technique will be used more widely in view of the excellent results obtained (low morbidity with hardly any complications). PMID- 1509271 TI - [Urethroplasty for repairing recurrent urethrocele and loss of urethral substance: apropos of 41 cases]. AB - Recurrent urethrocele is not often successfully treated surgically because, as it is well known, pre-operative sterilization of the urethrocele is difficult, especially when it is very large. Furthermore the incomplete excision of the corpus callosum, because of the loss of urethral tissue this involves, often leads to post-operative fistulas and stenoses. This is why, very often, there are relapses no matter what technique is adopted. In 1978 both Juraschek and ourselves published a technique, derived from Monseur, in which the urethrocele and the corpus callosum were completely excised. The resulting loss of urethral tissue was remedied with the albuginea from the ventral surfaces of the corpora cavernosa after a 180 degrees rotation of the urethra. The results of this treatment in 41 cases of recurrent urethrocele are given in this paper. The follow-up period for the patients was from 15 to 2 years. Results have been excellent with very few complications (2 post-operative fistulas and 2 urethra stenoses). There have been no relapses. PMID- 1509272 TI - [Concentration of aztreonam in plasma, urine, and seminal fluid of patients with chronic prostatitis]. AB - The authors consider the concentration of antibacterial drugs in the seminal fluid as a reliable experimental model for the study of pharmacokinetics in chronic prostatitis (c.p.). The study was conducted on 32 subjects, 20 of whom were affected by c.p. and 12 were normal controls. All subjects were treated with aztreonam at a dosage of 1 g.i.m. The assay was performed 1 hour after the injection, on seminal fluid, urine and serum samples. No difference was observed between normal subjects and patients with c.p. with regard to serum and urinary levels of the drug. There was a trend towards a higher concentration of the drug in the seminal fluid of patients with c.p. when compared to normal subjects, with mean values of 1.8 and 0.9 mcg/ml respectively. This difference was not statistically significant. Furthermore, the drug concentration of the drug in semen was below the sensitivity limits of the assay in 43% of normal subjects and in 10% of patients with c.p. In the latter group of patients the mean values of aztreonam concentration exceeded the minimal inhibitory concentrations for most aetiological agents causing c.p. In conclusion, it is suggested that aztreonam is likely to be effective in acute prostatitis, caused by Gram negative strains and may be indicated in selected cases for the treatment of c.p. PMID- 1509273 TI - Extracorporeal shock wave lithotripsy for urinary stone disease: our experience. AB - The authors report results of an 18 month study on ESWL treatment for calculosis of different tracts of the urinary apparatus. Average success rate is 80%, even if it varies depending on the site and size of the calculus. Surgery and PCN are required only in cases of unsuccessful treatment or particular forms of lithiasis. ESWL has determined advanced in the treatment of renoureteral stones in the last decade. However some significant generalized complications observed in our patients at follow-up raise doubts concerning possible, unforeseable long term effects of ESWL treatment. PMID- 1509274 TI - [Metabolism and action of L-carnitine: its possible role in sperm tail function]. AB - The authors report a review on the L-carnitine effects on the male genital tract. L-carnitine represents a cofactor in the transport of long chain fatty acids inside mitochondria and their subsequent oxidation. Therefore, its main role is that of intramitochondrial vehicle of acyl groups. In particular, the effects of L-carnitine on the male genital function seem connected mainly with the high concentration of L-carnitine in the epididymis; the uptake of the L-carnitine from the blood is an active, in part androgen-dependent, mechanism. Moreover, epididymal spermatozoa are able to concentrate L-carnitine (while they become progressively more impermeable to such a substance) during their passage from the caput to the cauda epididymis. The main function of the L-carnitine in the epididymis is to give to the spermatozoa an energetic substrate. In fact, this function should be of great importance since the epididymal spermatozoa employ fatty acid oxidation for their energy metabolism; on the contrary, the ejaculated sperm employ glycolytic process. As a consequence of the above-mentioned effects of L-carnitine the dosage of this substance in the evaluation of the integrity of the processes of maturation of the spermatozoa was proposed. Finally, there is growing interest in the use of L-carnitine as a therapeutic tool in some forms of male infertility. PMID- 1509276 TI - Molecular targets to overcome radioresistance. AB - Our laboratory has cultured cells from 23 patients with head and neck carcinoma and 13 patients with soft tissue sarcoma. The data suggest that, in some patients, inherent tumor cell radioresistance contributes to radiotherapy failure. This paper examines possible mechanisms that lead to increased cell survival following radiation exposure, and their potential as targets to overcome the radioresistant patient population. PMID- 1509275 TI - Granulocyte-macrophage colony-stimulating factor (GM-CSF): preclinical and clinical investigations. AB - In conclusion, hematopoietic growth factors have been shown to enhance the recovery and function of circulating WBCs after standard-dose cancer therapy or high-dose cancer therapy with ABMT, and preliminary data strongly suggests that these agents may have the ability to restore leukocyte numbers and competence in AIDS, myelodysplastic syndromes, and other marrow failure states. Phase I and II trials of GM-CSF in patients with AIDS, cancer, marrow failure states, and following bone marrow transplantation have been published, and limited phase III randomized trial experiences have been reported as well. Overall, GM-CSF represents a fascinating molecule with which to modulate human hematopoiesis in vivo. The multilineage stimulatory effects of GM-CSF that are evident in vitro have not been striking or consistent in clinical trials. However, the effects of GM-CSF on the production and function of mature neutrophils, monocytes, and eosinophils have been noted in the vast majority of clinical scenarios in which this cytokine has been tested. The clinical benefits of GM-CSF have, to date, only been proven in large-scale randomized studies of recovery from ABMT for lymphoid neoplasms. However, further data regarding the use of GM-CSF in other clinical settings have been generated, and the final results are eagerly anticipated by the oncology community. The beneficial effects of GM-CSF following ABMT consisted not only of a shorter period of absolute neutropenia, but also fewer significant infections, a diminished requirement for intravenous antibiotic administration, and a shorter overall duration of inpatient hospitalization. The use of GM-CSF in clonal disorders of hematopoiesis, such as myelodysplasia or myeloid leukemias, requires caution before such applications can be routinely recommended, and the demonstration of safety in this setting from large randomized trials will be needed. Preliminary data from small randomized trials suggests that the incidence of evolution to leukemia in patients with myelodysplasia and the number of patients with regrowth of leukemia after induction treatment in relapsed patients with AML may not be significantly different than in patients who do not receive GM-CSF. Various neutropenic conditions (eg, idiopathic or congenital) may respond clinically to hematopoietic growth factors such as GM-CSF. Patients treated for 3 to 15 months continue to respond with significantly increased granulocytes and resolution of prior infection. The subcutaneous route of administration is convenient and patients seem to accept it readily. It is difficult to determine the extent to which adjunctive therapy with GM-CSF will be cost effective.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1509277 TI - Biochemical pharmacology of chemotherapeutic drugs used as radiation enhancers. AB - Radiotherapy and chemotherapy are often administered concurrently in an attempt to take advantage of postulated biochemical or molecular interactions between the two modalities. It is generally assumed that the drugs influence some mechanism of radioresistance rather than that radiation has any direct effect on the mechanisms of cell kill by chemotherapy. Many classes of drugs have been found to interact with radiation. Classic radiosensitizing agents include the halogenated pyrimidines and the nitroimidazoles; however, many conventional cytotoxic agents, such as hydroxyurea, 5-fluorouracil (5-FU) and cisplatin, also enhance cell kill by radiotherapy. Hydroxyurea has been shown to inhibit excision-repair of thymine dimers and single-strand DNA breaks induced by radiation. Exposure of cells to 5 FU following radiation produces synergistic cytotoxicity in several model systems. The precise cellular mechanisms by which 5-FU and radiotherapy interact have not been defined, although inhibition of repair of radiation-induced DNA damage has been postulated to occur. Cisplatin has also been shown to enhance the cytotoxicity of radiation in both cell culture and tumor-bearing animals, although the mechanisms of the interaction have not been defined. Hydroxyurea, 5 FU, and cisplatin also undergo a number of biochemical interactions that enhance their cytotoxic effects. Thus, a rationale exists for employing these drugs in combination with radiation. Additional studies are required to understand the mechanisms of drug-radiation interactions and to determine the optimal scheduling of these therapies. PMID- 1509278 TI - The experimental and clinical rationale for the use of S-phase-specific radiosensitizers to overcome tumor cell repopulation. AB - Clinical and laboratory evidence suggests that several common human cancers contain populations of rapidly proliferating clonogens that may have a substantial impact on local control following conventional radiotherapy. Strategies to improve locoregional control include the use of S-phase-specific radiosensitizers, such as the halogenated pyrimidine analogues (5 iododeoxyuridine, 5-bromodeoxyuridine, fluorodeoxyuridine, 5-fluorouracil) and hydroxyurea. These drugs are taken up and metabolized only by cells synthesizing DNA so that increased tumor proliferation should result in increased radiosensitization. Although the initial clinical trials with these agents were inconclusive, several recent reports have rekindled interest in these radiosensitizers. Ongoing laboratory research has provided further insight into the basic mechanisms of radiosensitization. However, many questions remain unanswered. We will review the data that suggest rapid tumor proliferation, experimental studies with the S-phase-specific drugs, and the results of clinical trials. We will also consider the possible design of future trials based on our current understanding of tumor proliferation and the mechanisms of radiosensitization of S-phase-specific agents. PMID- 1509279 TI - Use of hypoxia-directed drugs in the therapy of solid tumors. AB - Solid tumors in experimental animals and human patients contain areas in which transient or persistent perfusion deficits lead to the development of hypoxia, low pH, and nutritional deprivation. These microenvironmental inadequacies induce resistance to ionizing radiation and to many antineoplastic drugs, but also offer mechanisms that can be used to target certain drugs to solid malignancies. Regimens incorporating hypoxia-directed drugs as adjuncts to radiotherapy or conventional chemotherapy can be used to increase the therapeutic ratio by increasing local tumor control without producing a concomitant increase in toxicities to normal tissues. PMID- 1509280 TI - Simultaneous treatment with single-agent chemotherapy and radiation for locally advanced cancer of the head and neck. AB - A substantial proportion of patients with squamous cell carcinoma of the head and neck have extensive locoregional disease at presentation. While extensive surgical procedures may completely eradicate local disease with acceptable morbidity for smaller tumors, in patients with stage III and IV disease, high local relapse rates and relatively short survival times still characterize the course of the majority of such patients. For patients with locally unresectable disease, the combined use of chemotherapy and radiation has resulted in encouraging data both in terms of local control and survival. Combined-modality programs frequently employ platinum coordination complexes, and standard or hyperfractionated radio-therapy toxicity data suggest that the overall tolerance of such programs is acceptable and, more important, long-term follow-up has shown that function can be largely preserved. In this review we illustrate the experience with combined single-agent chemotherapy and radiotherapy, and discuss the methodologic difficulties of clinical trials in this setting. We describe our experience with combined carboplatin and simultaneous conventional radiation in patients with extensive unresectable locoregional disease. Encouraging results and modest toxicity clearly support further testing with this approach, especially in patients with less advanced and bulky disease. PMID- 1509282 TI - Treatment of locoregional esophageal cancer. AB - Since the mid 1970s combined-modality treatment has been investigated for locoregional cancer of the esophagus. Single-institution pilot studies of preoperative cisplatin-based chemotherapy have shown that 40% to 60% of patients with squamous cell carcinoma achieve a partial response, while an occasional patient has a pathologically documented complete response (CR). Two randomized trials involving small numbers of patients have not confirmed the survival benefit for preoperative chemotherapy that some pilot studies suggested. A large, multicenter intergroup trial is in progress, comparing preoperative and postoperative cisplatin/5-fluorouracil chemotherapy with immediate surgery, and includes both squamous cell carcinoma and adenocarcinoma histologies. Preoperative chemoradiotherapy programs have used survival and pathologic CR as end points. Single-institution and multicenter pilot studies have consistently reported pathologic CR in 25% to 30% of patients. Median survivals have varied from 12 to 29 months. The results from multicenter pilot trials are at the lower end of this range, with more encouraging results coming from single institutions. One randomized trial in progress compares a 3-week intensive cisplatin/vinblastine/5-fluorouracil and concurrent radiotherapy regimen followed by surgery with immediate surgery. No completed comparative trials have been published. Chemoradiotherapy without surgery is a more recent approach stimulated both by the poor survival rates with primary surgery and by its associated morbidity and mortality. The results of the intergroup randomized trial of concurrent cisplatin 5-fluorouracil/radiotherapy versus radiotherapy alone have demonstrated a role for chemotherapy. Median survival and 12- and 24-month survival improved significantly with the combined-modality treatment. This treatment program is now recommended for patients with locoregional disease who are not candidates for surgery. The optimal management of patients with esophageal cancer is still unknown. Accurate methods to stage patients clinically and to identify prognostic factors are needed. The randomized trials in progress evaluating preoperative and postoperative chemotherapy and preoperative chemoradiotherapy are essential to move forward with improved treatment strategies. PMID- 1509281 TI - Perspectives on combination chemotherapy with concomitant radiotherapy for poor prognosis head and neck cancer. AB - Concomitant chemoradiotherapy has resulted in small increases in disease-free or overall survival for patients with advanced head and neck cancer when single agent chemotherapy is used. To increase the efficacy of this approach, combination chemotherapy also has been explored. In this setting, acute toxicities are frequently increased, necessitating interruption or protraction of radiotherapy. Despite this fact, pilot trials using 5-fluorouracil-based chemotherapy have indicated high response and encouraging survival rates. Some of these trials will be reviewed, with a focus on studies with 5-fluorouracil, hydroxyurea, and cisplatin conducted at the University of Chicago. PMID- 1509283 TI - Malignant mesothelioma: diagnostic and management strategies for 1992. AB - Malignant mesothelioma of the pleural and peritoneal surfaces is epidemiologically linked to crocidolite, a long, thin, and rigid form of asbestos whose use has been dramatically curtailed within the past 20 to 25 years. The incidence of disease may have peaked around 1984 and may now be declining. The highest incidence of disease occurs in elderly white men (greater than or equal to 75 years old). The histology of mesothelioma is classically biphasic, with both epithelioid and sarcomatous areas present. Independent pathologic review can be useful, and a variety of special stains should be used, if diagnosis is unclear. Electron microscopy and serum carcinoembryonic antigen levels are also useful. Surgical treatments have been difficult, but 3-year survival rates range from 15% to 36%. Unfortunately, only about 20% of all diagnosed patients are candidates for aggressive surgical approaches. Radiotherapy likewise has been disappointing, although occasionally useful. Lastly, 13 single-agent chemotherapy trials conducted on 302 patients using 10 different commercially available drugs have failed to identify a consistently effective agent. Combination chemotherapy has also not proven effective and, therefore innovative new approaches are needed. PMID- 1509284 TI - Therapeutic relevance of pharmacokinetics and pharmacodynamics. AB - Most antineoplastic drugs have a narrow therapeutic index. The medical world's incomplete understanding of the variability of pharmacokinetics and pharmacodynamics has led to dosing problems with these agents. Basic understanding of linear and nonlinear pharmacokinetic models as well as interpatient and intrapatient variability is necessary to optimize dosing. Pharmacodynamic information relates pharmacokinetic information to clinical outcome. PMID- 1509285 TI - Concurrent chemoradiation in carcinoma of the uterine cervix. AB - Carcinoma of the cervix is most commonly treated with radiotherapy when the disease is locally advanced. Tumor bulk often limits the efficacy of this therapy, as does the tolerance of adjacent healthy tissue. Cytotoxic chemotherapeutic agents have been used with concomitant radiotherapy. Extensive data are available on dose and schedule tolerance for cisplatin, 5-fluorouracil, and a number of combination regimens. Phase III data that confirm any advantage in terms of local control, disease-free survival, or overall survival have been published only for hydroxyurea. Hydroxyurea, an S-phase-specific inhibitor of ribonucleotide reductase, lacks single-agent activity against metastatic, squamous cell cervical cancer. Further studies are required before agents other than hydroxyurea can be considered standard therapy with concomitant radiotherapy for locally advanced carcinoma of the cervix. PMID- 1509286 TI - Chemoradiotherapy in locally advanced bladder carcinoma. AB - Bladder carcinoma represents the fifth leading cause of cancer in the United States. For patients with muscle-invasive tumors, radical cystectomy has been the treatment of choice, yet over 50% of such treated patients are destined to develop recurrent disease. In order to minimize morbidity in patients with invasive disease, bladder-sparing techniques using radiotherapy alone, or with chemotherapy, have been investigated. While it is clear that durable complete remission can be achieved in some patients, the results to date require additional follow-up to determine the optimal cohort of patients destined to benefit from this approach. It is hoped that ongoing prospective trials will delineate this population. PMID- 1509287 TI - Combined radiotherapy and chemotherapy in the treatment of gastrointestinal malignancies. AB - There has long been an interest in the use of combination chemotherapy/radiotherapy in the treatment of gastrointestinal tumors. Almost all such regimens combined 5-fluorouracil (5-FU) with radiotherapy. Work has been done in gastric cancer, pancreatic cancer, and colon and rectal cancer, all of which demonstrate an advantage in certain clinical situations for combined modality therapy. In locally advanced pancreatic cancer, radiotherapy/5-FU has been shown to improve survival compared with radiotherapy alone, while in resectable carcinoma of the pancreas, the combination has been demonstrated to improve long-term survival compared with surgery alone. In patients with gastric cancer the data are more limited, but indications are that combined-modality therapy may benefit certain subsets of patients. Little information exists in colon cancer, but patterns of failure suggest a potential role for adjuvant radiotherapy/5-FU. Studies are being designed to test the hypothesis. In rectal cancer, a significant amount of data exists to support the value of radiotherapy/5-FU-based chemotherapy as an adjuvant in patients with stages B2 and C tumors. At present, studies are being run or analyzed to define whether modulation of 5-FU with leucovorin or levamisole, or whether the use of continuous infusion 5-FU, will improve the therapeutic efficacy of the adjuvant therapy. PMID- 1509288 TI - Intravenous gammaglobulin therapy: current role in bone marrow transplant, malignancy, and immune hematologic disorders. PMID- 1509289 TI - Pure red cell aplasia: treatment with intravenous immunoglobulin concentrate. PMID- 1509290 TI - An assessment of the safety and tolerability of immune globulin intravenous (human) Sandoglobulin prepared in sterile water or 5% dextrose at various concentrations. PMID- 1509291 TI - Statistical methods for the analysis of repeated measurements of serum immunoglobulin levels. PMID- 1509292 TI - Continuous infusion intravenous immunoglobulin is associated with a reduced incidence of infection and achieves higher serum immunoglobulin G levels than intermittent infusion following bone marrow transplantation. PMID- 1509294 TI - Graft-versus-leukemia without graft-versus-host disease: an elusive goal of bone marrow transplantation. PMID- 1509293 TI - Advances in the diagnosis and management of myeloma. PMID- 1509295 TI - Therapeutic use of immunotoxins. AB - Much progress has been made in the therapeutic use of immunotoxins since the first clinical trials, especially in the prevention and treatment of AGVHD. This is also further discussed in this symposium by Champlin. Research in immunotoxin use has gone beyond cancer and into the treatment of immunologic disorders, such as rheumatoid arthritis and HIV infection. Before further advances can take place several problems must be overcome, including the rapid clearance of immunotoxin by the liver, the generation of anti-immunotoxin antibodies, and poor penetration by the immunotoxin in solid tumors. Other obstacles to the wide use of immunotoxins are the heterogeneity of tumor cells, the shedding of tumor antigens into the circulation, and the inability to identify neoplastic renewal cell specific antigens that are not cross-reactive with normal tissues. Despite these obstacles, the early success of immunotoxins, especially in hematologic malignancies, reinforces the feasibility of designing rational targeting reagents in cancer therapy. PMID- 1509296 TI - Can intravenous immunoglobulin treatment regulate autoimmune responses? PMID- 1509297 TI - Role of intravenous immunoglobulin G in autoimmune hematologic disorders. AB - The data presented in this review established IVIG therapy as an important treatment modality in the autoantibody-mediated cytopenias and coagulation disorders of both children and adults. The immediate response to therapy is thought to be related to nonspecific Fc-receptor blockade of mononuclear phagocytes in the reticuloendothelial system (autoimmune cytopenias), or to idiotypic antibody interaction with pathologic autoantibodies (in acquired coagulation disorders). Although less frequent, long-term responses to IVIG therapy are reported. Such responses must involve an immunomodulating effect of IgG that influences T- and B-cell function, with inhibition of pathologic autoantibody formation. It is possible that idiotypic antibody interactions play a part in long-term responses. The experience with IVIG therapy in the decade following Imbach's important observations reported in 1981 has provided a sound data base regarding the use of this important therapy in patients with autoimmune hematologic disorders. The challenge of the next decade should be to further investigate mechanisms of action of this important therapy and to conduct carefully controlled studies to answer specific clinical questions. Examples of such questions include the following: (1) Can IVIG therapy, administered early in the course of illness in selected children with acute ITP, decrease the incidence of chronic ITP?; (2) Is maintenance, high-dose IVIG therapy a cost-effective method for the management of patients with chronic ITP refractory to corticosteroid therapy and splenectomy?; and (3) Can IVIG therapy administered to selected pregnant women with ITP significantly reduce the incidence of serious thrombocytopenia in their offspring? In conducting these studies, consideration should be given to the type of IVIG preparation used and to the treatment protocol implemented. It is evident that responses to unmodified IgG preparations (with the Fc-receptor part of the molecule left largely intact) are superior to preparations that have been modified during preparation. Responses are also likely to be dose-related. The data reported for IVIG therapy in patients with acquired factor VIII deficiency suggests that the idiotypic antibody content of IgG preparations is also of importance; if so, preparations selected from specific donor pools (for example, multiparous women) known to contain higher levels of circulating autoantibodies (than those from primiparous women or untransfused males) may provide a degree of benefit not seen with standard IVIG preparations. It is therefore important that clinicians and laboratory specialists work closely together in the design and conduct of future clinical trials initiated to answer those important clinical questions raised by the first decade of observations with IVIG therapy for autoimmune hematologic disorders. PMID- 1509298 TI - Alloimmunization to platelet antigens. AB - Alloantibodies to platelet-specific antigens can cause significant thrombocytopenia and bleeding in NATP and PTP. IVIG plays an important role in the therapeutic regimen of both of these disorders. Alloantibodies in the multiply transfused patient bind to HLA class I and platelet-specific antigens. IVIG has not improved response to random-donor platelets in refractory patients, but there may be a role for IVIG in critically ill and bleeding patients, in combination with HLA-matched platelets. PMID- 1509299 TI - Psychosocial problems in primary care: some results from the Dutch National Study of Morbidity and Interventions in General Practice. AB - According to standardized screening instruments, mental distress is a common phenomenon among many patients who visit their general practitioner. However, a number of patients who seem to be in need of mental help do not put forward such a demand for help, whereas other patients who express psychosocial problems to their GP are not considered to be in need, according to a standardized measure. In this paper, a distinction has been made between the objectified needs of the patient as expressed by a standardized assessment, and the demands of the patient, expressed by the Reason for Encounter, stated during their visit at the GP. Results of a follow-up study of two cohorts of patients have been presented: one cohort presented during a 3 month period at least one articulated demand for psychosocial help, a second cohort presented at least one somatic complaint, considered by the GP as being psychological by character, without presenting any psychosocial complaint in that period. Objective needs for mental help of patients in both cohorts were assessed by means of the General Health Questionnaire. During one year all consultations of these two cohorts were registered. The following questions have been put forward: what demands for help have been put forward by the patients, what treatment have these patients got, and what has been the course of the problems during one year of patients with different needs and demands. From the results the following conclusions may be drawn: many patients with a probable mental illness (according to their objective need) present only physical symptoms.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1509300 TI - Policy directions in urban health in developing countries--the slum improvement approach. AB - The urban development, or housing, sector has a longer experience of addressing the problems of the urban poor in developing countries than the health sector. In recent years the policy of 'slum improvement', which involves both sectors, has attracted the support of international donors. This article documents the development of the slum improvement approach and addresses key issues of the approach which have implications for health planning: covering the poorest dwellers; relocation; land tenure; gentrification; debt burdens and the impact on women. Questions about the approach which still need answering are defined and a summary of the constraints in slum improvement and potential solutions is presented. PMID- 1509301 TI - Sexually transmitted disease, ethnomedicine and health policy in Africa. AB - Compared with both industrialized countries and other less developed parts of the world, most of sub-Saharan Africa suffers inordinately from sexually transmitted diseases (STDs). It has high prevalence rates of traditional STDs, such as gonorrhea and syphilis, and if accurate seroprevalence surveys were to be done, it would probably prove to have the highest HIV seropositive incidence in the world. Unlike the pattern in the West, AIDS is primarily a heterosexually transmitted disease in Africa. This appears to be largely because of the prevalence of other untreated or improperly treated STDs. Therefore to lower the incidence of STDs would be to curtail the spread of HIV infection. The problem becomes how exactly to accomplish this. Most STD cases are never even presented at biomedical health facilities; they are presented to traditional healers. Both healers and their patients seem to believe that traditional STD cures are more effective than 'modern' cures, although the former are probably biomedically ineffective. While there is scant ethnomedical literature on STDs in Africa, the present paper presents Swaziland findings and related evidence from other African societies that the ultimate cause of several common STDs is believed to be the violation of norms governing sexual behavior, requiring traditional rather than biomedical treatment. Traditional healers therefore need to be a central part of any scheme to lower the incidence of STDs. PMID- 1509302 TI - Malaria: ethnomedical perceptions and practice in an Adangbe farming community and implications for control. AB - Malaria is a parasitic disease about which there is much bio-medical knowledge on causation, prevention, treatment and control. Attempts at eradication, as well as control in the past has been mainly a technical and bio-medical endeavour. With the policy shift from world wide eradication of malaria to control as part of primary health care, there is increasing interest in studying all possible determinants of the problem at local as well as regional levels as part of the search for an effective intervention. This paper presents the results of a study into community perceptions and practice relating to causation, treatment and prevention of malaria in a rural Adangbe farming community in Southern Ghana. Malaria is common in this community. Crude parasite rates among adolescent girls (10-19 years old) in the community were 49% towards the end of the major rainy season, and 47% in the early dry season. The symptoms and signs of the disease are readily described by lay people as well as traditional healers. Diagnosis and treatment of uncomplicated episodes of malaria at home, according to ethnomedical perceptions, is the predominant behaviour in this community. Very few cases of uncomplicated malaria are sent to health facilities. Ethnomedical perceptions of malaria causation and treatment on which this self care is based, are different from conventional biomedical ones. Malaria is perceived as an environmentally related disease caused by excessive contact with external heat which upsets the blood equilibrium. Many community members do not connect it with the mosquito in theory or practice. Implications for approaches to control are discussed. PMID- 1509303 TI - Quality of Life in patients with resected oesophageal cancer. AB - Quality of Life (QL) is hard to assess and seldom measured in patients having carcinomas with an unfavourable prognosis. Oesophageal cancer is one of the malignancies with a low 5-year survival rate. Dysphagia (problems in swallowing food) is considered to be the most important indicator of QL in patients with oesophageal carcinoma. Moreover, the psycho-social aspects and subjective QL in cancer have recently gained importance. The present study investigated QL in a 132 patients with oesophageal cancer. Eighty-three of them had a surgical operation (removal of part of the oesophagus and part of the stomach, followed by a reconstruction of the digestive tract). Sixty-seven patients filled in questionnaires before and after the operation. Complete sets of data were obtained from 62 patients. Time interval between operation and postoperative assessment varied from 3 to 7 months. Indicators of QL were: Psychological Distress, Physical Symptoms, Global Evaluations, Activity Level, Swallowing Problems and Food Intake. Swallowing Problems showed moderate correlations with the other QL indicators. Physical Symptoms increased, whereas the Activity Level, Psychological Distress, and Swallowing Problems decreased; Global Evaluations remained unaltered. PMID- 1509304 TI - Syphilis, sex and crack cocaine: images of risk and morality. AB - A new epidemic of syphilis in the Portland, Oregon metropolitan region mirrors a national trend in the United States. The epidemic is centered in urban areas, is associated with heterosexual transmission, and disproportionately affects people of color, especially African-Americans. The epidemic has been linked to sexual activity among users of crack cocaine, and particularly to the practice of trading sex and crack. Here, we report an analysis of in-depth interviews of 40 respondents, of whom 31 have used crack cocaine, 12 have experience as professional sex workers (prostitutes), and 12 are confirmed recent syphilis cases or their sexual contacts. These respondents confirm that sexual activity involving multiple anonymous partners often takes place within the context of crack cocaine use. They also describe sexual activity among more casual users of the drug. But respondents present themselves as having maintained an adherence to common American values regarding cleanliness, mortality, and sexual behavior. They speak of choosing sex partners according to whether a prospective partner 'looks clean.' This image of cleanliness goes beyond simple bodily hygiene, and into the realm of judgement about moral character. A person is more likely to be judged clean if he or she is known to come from a nice family, has a pleasant demeanor, or appears concerned about self-control. Such people are seen as fundamentally decent, and therefore less likely to have syphilis, a disease associated with deterioration, tearing down, dirtiness and disordering. Thus, respondents use conceptions of cleanliness and morality in constructing definitions of high- and low-risk sexual behavior, as they negotiate a life that endangers their sense of moral control. In doing this, they invoke beliefs and values central to the dominant culture surrounding them. This points to the limits of defining crack cocaine users, and other communities of drug users, as being culturally different from the rest of us. PMID- 1509305 TI - Economic appraisal of asthma and COPD care: a literature review 1980-1991. AB - Despite the considerable burden and costs of illness and despite the increasing need to set priorities on the basis of efficiency considerations, only 20 economic appraisals of asthma and COPD care have been published during the past 11 years. This paper provides a detailed summary of the cost-effectiveness 'evidence' given by these studies and a discussion of relevant methodological issues. The studies comparing programme costs of delivery methods for oxygen and for aerosol bronchodilator drugs, provide the most straightforward evidence in favour of the concentrator and the metered dose inhaler respectively. There also seems to be evidence in favour of hospital-based home care programmes as compared to community-based home care programs. Health education, especially directed at asthmatic children seems to reduce health care costs and improve attitude, compliance behaviour and self-management skills. Information on the cost effectiveness of pharmacotherapy and diagnostic technologies, both important interventions in asthma and COPD, was found to be totally lacking. PMID- 1509306 TI - Kidney procurement policies in the Eurotransplant region. 'Opting in' versus 'opting out'. AB - A shortage of kidneys has been part of kidney transplantation ever since it evolved from its experimental stage and became a therapeutic possibility. However, at present this shortage is more acute than ever before. Post mortem kidney procurement policies can be distinguished into 'opting in' and 'opting out' systems. In the five countries cooperating in Eurotransplant, systems of both kind have been implemented. In this paper the relation between these procurement policies and kidney availability in the Eurotransplant region is examined. The opting out system turns out to be more favourable to kidney procurement than the opting in system. The approach of the next of kin with the donation question happens to be an important barrier for kidney procurement in the opting in system, but fails to appear under opting out. In the epilogue some remarks are made on the possibilities of introduction of the opting out system in countries now applying opting in. PMID- 1509307 TI - A classification of psychological distress for use in primary care settings. AB - This paper contrasts three ways of conceptualizing emotional distress in general medical settings: high scorers on screening tests, 'cases' according to the doctor seeing them, and standardized research diagnoses. It is shown that distress as measured by screening test is very much more prevalent than research diagnosis, and yet doctors working in general medical settings need to be able to conceptualize disorders using a classification that is helpful for them. The proposed classification is based upon the patient's need for intervention, and it distinguishes the few who need to be thought of as having a formal mental disorder from the many who do not. It takes account of what is known about 'labelling' and compliance, and it is linked to the skills needed by primary care workers. The largest group consists of those whose emotional distress needs recognition and discussion; the next group also needs social interventions; while the final group benefits from recognition of a mental disorder which necessitates a medical or psychological treatment. PMID- 1509308 TI - Mortality from selected cancers in NSW and Sydney, Australia. AB - This study utilizes unit list mortality data for New South Wales, Australia in differential mortality analysis, at state and local levels, and examines geographic patterns of stomach, colo-rectum, respiratory system, female breast cancer and total cancer mortality in Sydney. Associations between manual occupations, low socioeconomic status and male stomach and respiratory cancer mortality were found, as were higher mortality from stomach and respiratory cancer among European-born immigrants in manual occupations. However, unexpected associations were also found between high mortality from stomach and respiratory cancers and managerial occupations. There were also more acute associations between colo-rectum and female breast cancer and higher status areas. Further, mortality variations between specific occupational groups occurred when martial status was controlled for, and the strongest variations were between married and never married males where the social isolation risk factors were presumed to be operative. The highest mortality at the local level in Sydney occurred where more than one at risk population resided and where other influences may have been operative. PMID- 1509309 TI - Professional reimbursement and management of time in general practice. An international comparison. AB - A hypothetical model was proposed for explaining the relationship between general practitioners' system of payment and the amount of time spent in patient and non patient work. It was hypothesized that GPs reactions to higher workload vary according to the payment system. In this paper we compare two health care systems which have both mixed systems of payment of GPs. In England and Wales up until April 1990 GPs are partly paid by capitation (approx 45% of their income), partly by allowance (38% of their income) and for a much smaller part fee for service (18% of their income). In the Netherlands GPs are paid by capitation for the publicly insured patients (63% of the average practice list) and fee for service for the privately insured patients. We expect (among other things) a stronger, positive relationship between list size and hours worked in the Netherlands and a comparably strong, negative relationship between list size and booking intervals in the Netherlands and in England and Wales. Drawing on data collected from national surveys of GP workload in the Netherlands and England and Wales these propositions were examined. The results of this comparative analysis showed some support for the propositions in that the relation between list size and number of hours worked in patient related activities is stronger in the Dutch setting than in England and Wales, and about the same strength for the relationship between list size and booking intervals. PMID- 1509310 TI - Integrating conflicting professional roles: physician participation in randomized clinical trials. AB - The traditional identification of physicians as either clinician or researcher is challenged by the emergence of randomized clinical trials (RCTs) where research and clinical care are performed simultaneously. A mail survey using a self administered questionnaire, the Physician Orientation Profile, was conducted of 101 physicians from the Collaborative Ocular Melanoma Study (COMS), a set of trials which compares surgical removal of the eye with radiation in the treatment of medium sized eye cancers. A 95% response rate was obtained; follow-up telephone interviews were conducted with 87% of respondents. Key findings suggest that RCTs challenge traditional definitions of physician's 'core task,' because they participate in a social process that requires them to integrate the formerly disparate and sometimes competing roles of researcher and clinician. Three implications of this integration are discussed: amending the expert reward system, altering customary clinical practice and redefining reference groups for professional interaction. PMID- 1509311 TI - [Total prosthesis of the hip joint for traumatic indications (VUTSCH data from 1985-1990)]. AB - The authors analyze all total endoprostheses which were performed at their department in 1985-1990 for traumatic indications--an injury or its immediate sequelae: 6 times an implantation was made because of fracture, 11 times because of failure of primary synthesis or serious aseptic necrosis of the head after synthesis. There were no prostheses on account of late deforming arthritis which developed on a posttraumatic background. Seventeen total endoprostheses made on account of traumatic indication account for 7.4% of all total endoprostheses during the period of investigation. One patient died from pulmonary embolism after the operation, although heparin prevention was used and one patient developed a minor complication. All eight patients who were checked on average after 22.4 months following implantation had excellent or good results. The authors reached the conclusion that total endoprostheses should be indicated more frequently to the benefit of younger casualties and that the total numbers of total endoprostheses on account of traumatic indications are low. Therefore it is necessary to concentrate alloplasties mainly on orthopaedic departments which have experience also with other indications. Certain types of fractures of the neck and head of the femur or acetabulum cannot treated nowadays as effectively by any other technique. PMID- 1509312 TI - [Experience with non-surgical treatment of splenic injuries]. AB - Since 1980 in the department of paediatric surgery in Prague-Krc injury of the spleen is no longer an absolute indication for laparotomy and splenectomy. During the period from 1980-1990 46 children were admitted with an injured spleen. Of these 35 (76%) were treated conservatively, 11 children were operated. The number of conservatively treated patients increased in the course of time--during the initial period before 1985 65% children were treated conservatively, from 1986 to 1990 already 90% children. Only 16% children with an injured spleen treated conservatively needed a blood transfusion (on average 18.1 ml/kg body weight). This experience indicates that the great majority of children with an injured spleen can be treated by non-surgical methods. It is necessary to respect certain criteria which are given in the paper. Laparotomy is necessary in children with unstable vital functions, associated intraabdominal injuries and those to whom more than 30 ml blood per kg body weight must be administered. PMID- 1509313 TI - [Arterial injuries of the upper extremities]. AB - At the Department of Surgery in Pilsen in 1982-1991 a total of 26 patients with upper extremity vascular injuries was treated. Brachial artery was injured most commonly (50%). The direct trauma was responsible for 88.5% injuries, indirect injury was recorded in 11.5% cases only. The incidence of concomitant injuries of the vein, nerve or bone was 73.1%. Approximately one third of arterial injuries was caused by criminal offences. The vascular reconstruction was performed in all 26 patients. The overall patency rate was 84.6%, the amputation rate was 3.8%. One patient with polytrauma died of sepsis (3.8%). The authors give a comprehensive review of the causes, diagnosis and treatment of vascular injuries of the upper extremities. PMID- 1509314 TI - [The cervico-capital endoprosthesis in traumatology. Experience of the Traumatology and Special Surgery Research Institute 1985-1990]. AB - The authors submit an analysis of a group of 143 patients to whom in 1985-1990 in the Traumatological Research Institute in Brno a cervicocapital endoprosthesis was implanted. Indication for implantation was in all instances a fracture of the neck of the femur, most frequently a subcapital fracture--a total of 92. Women predominated 5:1. The mean age was 75 years, the range 37-93 years. In 119 patients the endoprosthesis was implanted on account of a new injury, in the remaining 24 on account of the sequelae of an injury. In 32 patients 1-4 operations preceded. The most frequent cause was a fall in the home. Fifteen patients were operated on the day of the injury and 80 were operated within five days after the injury. In the group 60 complications were recorded, 1-4 complications in 46 patients (32% of the group). The causes of complications are discussed. During the investigation 46 patients died (32% of the group), incl. half during the first hospitalization on account of the investigated injury. Only 27 patients of the group could be followed up, results are presented (excellent and good in 20 patients) and the reasons are discussed why patients cannot be followed up. Finally the authors conclude that in future it will be necessary to indicate endoprostheses as primary treatment more frequently, although secondary operations have similar results. The operation should be made as soon as the patient's condition permits it; the urgency is not acute as in syntheses; it should permit early mobilization of the patient. The unsatisfactory percentage of complications must be reduced by a complex of measures starting with organization of the workplace and the regime of the operating theatres and ending with the technical skill of the surgeon. The authors emphasize the problem of subsequent rehabilitation but do not analyze it in the present work. PMID- 1509315 TI - [Fractures of the upper part of the femur treated by means of the Ender osteosynthesis method]. AB - Intramedullary osteosynthesis by Ender's method proved very successful and easily managed from the technical aspect, while it causes relatively little discomfort to the patient and resolves the problem of fractures of the femur in the trochanteric area. The greatest advantages, as compared with other types of osteosynthesis, are that it is not as time consuming as other procedures, that it is a minor operation which reduces the incidence of infection and causes minimal stress to the patient. When careful anaesthesia is used, it is frequently the only operation which can be used in biologically old and high risk patients. PMID- 1509316 TI - [Distant metastasis of malignant melanoma in the small intestine, 2 case reports]. AB - The authors present the case history of two patients with metastases of a malignant skin melanoma into the gastrointestinal tract. One case detected on operation, with concurrent affection of the adrenal gland, the second one with the symptomatology of occult haemorrhage. The paper is supplemented by a review of the literature covering the last five years. The authors recommend in the described cases an active surgical approach. PMID- 1509317 TI - [Reinforcement anastomoses in the small intestine with fibrin glue (experimental study)]. AB - In an experiment on baby pigs the authors tested the strength of an end-to-end anastomosis of the small intestine by atraumatic inverted silon stitches in one layer reinforced by a fibrin film along the circumference of the suture. Intraluminal pressure was increased 15 minutes after application of the glue and completion of the anastomosis. The differences in the strength of the simple suture and that reinforced by the fibrin coagulum are statistically significant. The fibrin-reinforced anastomosis is more resistant against increased intraluminal pressure. After resection of the damaged portion the passage was restored by a new anastomosis in one layer and reinforced by fibrin glue. Five minutes after the fibrin film had dried, the loop was returned into the peritoneal cavity. All experimental animals survived without damage for a period of six months. Histological examination of the preparation confirmed satisfactory healing by a smooth scar without reaction of the tissue to alien material. PMID- 1509318 TI - [The fibrin glue system in the care of experimental injuries of the spleen and liver]. AB - In experiments on 28 rabbits and 28 baby pigs the authors tested the effectiveness of a fibrin glue mixture prepared from locally available components in a fatal injury of the liver and spleen. The authors used an original system of application "Duplojekt" for simultaneous application. Using the technique of digital compression of the margins of the wound and simple application of the fibrin glue, they repaired extensive tissue injury. They investigated the time needed for haemostasis, for adequate adherence of the coagulum to the wound and adequate hardness of the coagulum. They recorded the total time of the operation and amound of glue used. They used two different concentrations of fibrinogen with a low and high value and a standard concentration of thrombin for rapid reaction and formation of the coagulum. The authors found equal haemostatic effects of the two systems and different times of the mixtures with a high and low fibrinogen value. The glue with the high fibrinogen concentration was more effective. Both systems with the low and high fibrinogen concentration are, however, effective and reliable. Treatment of an extensive injury was safe in all instances. All experimental animals survived the operation, and the postoperative period and were killed at the defined times. The selected method and elaborated technique are useful for clinical surgery. PMID- 1509320 TI - Youth attending Cape Peninsula day hospitals. Sexual behaviour and missed opportunities for contraception counselling. AB - Questionnaires were completed by a sample of youth (aged 15-24 years) attending day hospitals in the Cape Peninsula. Of the total sample of 225, 73.3% indicated that they had experienced sexual intercourse; of these, 27.3% had had 2 or more partners in the previous year, and on their last coital episode 91.0% had known their partner for more than 7 days and 52.8% had used some form of contraception. The criteria of a strict definition of missed opportunity for contraception intervention were fulfilled by 7.6% of the total sample, while 43.6% of those who had experienced sexual intercourse and 43.9% of those who had not did not receive contraception intervention but would have liked to have done so. Those who had had more than one partner in the previous year were more likely to have satisfied the strict definition of missed opportunity, while of those who had not had sexual intercourse, younger respondents and students were more likely not to have received contraception intervention despite wanting such intervention. It is concluded that all youth attending day hospitals should routinely be offered contraception counselling and that the issue of sexually transmitted diseases should be addressed simultaneously. PMID- 1509319 TI - Major complications associated with extra-amniotic prostaglandin F2 alpha termination of the mid-trimester pregnancy. AB - Extra-amniotic prostaglandin F2 alpha (PGF2 alpha) termination of mid-trimester pregnancy can be associated with serious complications, defined for the purposes of this study as unintended major surgery or death as a result of the termination. A retrospective study of 319 such mid-trimester terminations at Johannesburg hospital revealed that 3 patients required hysterectomy, 1 developed a large tear of the posterior cervix and 1 died suddenly during the procedure. We are therefore considering changing our methods for second-trimester terminations. PMID- 1509321 TI - Reasons for lack of condom use among high school students. AB - This exploratory qualitative study was undertaken to identify barriers to condom use among high school students in Natal. Phase 1, a group discussion, with 50 high school students of all races from 10 schools, revealed that 17 (34%) were sexually active, 8 (47%) of these had used a condom at least once, but none had used condoms in every sexual encounter. Phase 2 comprised 36 focus group discussions involving about 650 black high school students. These discussions confirmed the finding of phase 1 that high school students were not using condoms to any significant degree. In their opinion, condoms limited sexual pleasure, indicated a lack of trust in the partner's faithfulness, challenged the male ego, and were associated with sexually transmitted diseases. Their contraceptive properties were viewed with suspicion and considered undesirable by those teenagers who wished to prove their fertility. In addition, condom use was not sufficiently well understood and condoms were not accessible or available when required. We recommend that condom promotion strategies should include an adequate explanation of how condoms work and detailed information on their local availability. They should be available at a government-subsidised price through more accessible outlets; popular figures and recognised leaders should be encouraged to support anti-AIDS campaigns and condom use, particularly in the public media. PMID- 1509322 TI - A community paediatric information system--a tool for measles surveillance in a fragmented health ward. AB - A community paediatric geographical information system using hospital-based inpatient data was created to monitor longitudinal child health trends, to define paediatric priorities and to generate research ideas and interventions in a large and very fragmented health ward. This epidemiological tool has been used to describe measles admission trends over a 4-year period (1987-1990), which included a severe measles epidemic. The examination of these trends in progressively finer geographical categories has identified a number of areas with a particularly high incidence of measles and has provided useful guidelines for subsequent community-based research. The demonstration of low vaccination coverage in areas designated as high incidence areas by this system suggests that these trends are accurate and that they can reliably be used for routine measles surveillance. The use of this system for measles surveillance on a prospective basis is expected to enable workers in this area to identify any increase in measles incidence rapidly, to pinpoint where this increase is occurring, and to make it possible to respond in a more focused manner to outbreaks when they occur. PMID- 1509323 TI - The use of COSAS in the analysis of vaccination coverage in urban, peri-urban and rural populations in the Edendale/Vulindlela district of KwaZulu. AB - A repeat vaccination coverage survey has been conducted in the Edendale/Vulindlela district of KwaZulu. The survey data were processed using the Coverage Survey Analysis System (COSAS) developed by the World Health Organisation (WHO) through its Expanded Programme on Immunisation (EPI). A modified random cluster sampling method was used to select 281 children between the ages of 12 and 23 months. Of the children surveyed, 83% were in possession of Road-to-Health cards (RTHCs). The best estimate of overall coverage for doses up to and including the second doses of polio and diphtheria, pertussis and tetanus (DPT) was 85% or higher, but estimates for polio 3 and measles, at 72% and 67% respectively, remain suboptimal. Stratification of coverage into urban, peri urban and rural categories revealed that the major contribution to the fall-off in coverage, after the second dose of polio and DPT, came from children in the peri-urban category with estimates of 52% for polio 3 and 38% for measles. The fact that coverage in the peri-urban population for doses up to and including polio 2 was 78% or higher indicated that the peri-urban influence responsible for this drop-out effect occurred between the approximate ages of 5 and 8 months. This identified populations in informal peri-urban settlements as a priority group for urgent intervention and further study. The estimation of missed opportunities at visits when vaccinations are normally given, found in this survey to occur in 17% of children, was a useful feature of COSAS and provided a basis for a specific intervention. PMID- 1509324 TI - History of medicine. Paulesco. AB - Nicolas Constantine Paulesco achieved the unrecognised distinction of proving that an unknown but constituent factor of the pancreas controls the physiological value of the blood-sugar of a normal animal and that its absence is the cause of diabetes mellitus. His research in this particular field of medicine was carried out on dogs and his proof was the culmination of years of experimental work of precursors, colleagues and himself. This great advance, perhaps equivalent in some respect to the discovery of the therapeutic virtue of penicillin, remains unacknowledged. An exposition of the facts attendant upon this neglect follows. The reader is left to draw his or her own conclusion regarding the award of the Nobel Prize for Medicine in 1923. PMID- 1509325 TI - First reported case of alpha-mannosidosis in the RSA. AB - The first known case of alpha-mannosidosis in the RSA is reported. Presentation was classic, viz. delayed speech, kyphoscoliosis and hearing loss at the age of 4 years. Among the generally rare inherited lysosomal storage diseases, alpha mannosidosis is regarded in Europe and the USA as one of the more common disorders. It is suggested that the apparent underdiagnosis in South Africa may stem from lack of clinical recognition of a condition, which is relatively simple to diagnose biochemically. The clinical and radiological features of the child are described in the hope that clinicians will develop an awareness of the disorder, and include it in the differential diagnosis of deaf children who may also have mild skeletal abnormalities. Antenatal diagnosis of this untreatable condition is possible, so the birth of further affected children in a family could be prevented. PMID- 1509326 TI - Abdominal clamp, a variation on cramp. PMID- 1509327 TI - National co-operative trials in cancer in South Africa. PMID- 1509328 TI - National co-operative trials in cancer in South Africa. PMID- 1509329 TI - Poliomyelitis--down but far from out. PMID- 1509330 TI - Subacute sclerosing panencephalitis in the developing world. PMID- 1509331 TI - Adjuvant therapy after surgery for cancer of the colon. PMID- 1509332 TI - A new face of TB. PMID- 1509333 TI - Antenatal screening for HIV infection. PMID- 1509334 TI - Orthotopic liver transplantation at Groote Schuur Hospital. AB - We present data on 10 patients (5 men and 5 women, aged 21-56 yrs) with end-stage liver disease or tumour who underwent orthotopic liver transplantation at Groote Schuur Hospital between October 1988 and June 1991. Standard surgical techniques were used for procuring the donor liver, the recipient hepatectomy and the implantation of the liver. The venovenous bypass method was used in all but 2 patients. Postoperative immunosuppression was usually achieved with cyclosporin, azathioprine and low-dose steroids. Six patients were treated with prophylactic OKT3. Rejection episodes were treated with bolus doses of intravenous steroids. The indications for liver transplantation included chronic active hepatitis progressing to cirrhosis (5), biliary cirrhosis in association with inflammatory bowel disease (1), sclerosing cholangitis (2), alpha 1-antitrypsin deficiency (1), and tumour (1). All patients with chronic liver disease had experienced at least one complication, examples of which included encephalopathy, bacterial peritonitis, ascites, variceal bleeding and septicaemia. Serious postoperative complications included acute rejection of the transplanted liver, renal and liver failure that responded to intensive care support and medical management. One patient died on the 11th postoperative day with complications of bleeding oesophageal ulcer, shock and fungaemia. The remaining patients are alive and well 1-31 months after transplantation. PMID- 1509336 TI - AIDS--the Baragwanath experience. Part I. Epidemiology of HIV infection at Baragwanath Hospital, 1988-1990. AB - This four-part series describes the experience with HIV infection at Baragwanath Hospital to December 1990. In this first part we give an overview of the emergence of this disease and of its impact on the hospital. From July 1988 to December 1990, 426 HIV-positive individuals were identified: 58 were women identified in surveys at antenatal and gynaecology clinics, 60 were parents of infected babies or sexual contacts of hospitalised patients, and 30 were not inpatients (mainly patients at Soweto clinics). Of the 278 inpatients, 16 were identified in the latter 6 months of 1988, 54 in 1989 and 208 in 1990. Fifty-one per cent of the patients were in the adult medical wards, 11% in surgery, 20% in paediatrics and 18% in other disciplines. One per cent of sera from Wassermann reaction-positive women in mid-1990 were HIV-positive; this also applied to 1% of antenatal women in late 1990 and 2.7% of women with pelvic inflammatory disease. The HIV antigen assay is a useful adjunctive assay in the evaluation of HIV antibody-positive children. The false/true-positive ratio of a rapid HIV antibody test was 2:1 initially, but the specificity improved with experience. The use of rapid diagnostic assays for HIV must be restricted to laboratories with experience in reading assays and where definitive follow-up testing is assured. PMID- 1509335 TI - Anaesthesia for liver transplantation. The Groote Schuur Hospital experience. AB - In October 1988 the orthotopic liver transplantation programme recommenced at Groote Schuur Hospital. The experience gained from our first 10 patients is described here. Anaesthesia for this type of surgery is demanding given the long duration of the operation and the severe haemodynamic and physiological alterations that can occur. A rapid sequence induction is usually performed and anaesthesia maintained with fentanyl and isoflurane. Dopamine and mannitol are used for renal protection. Extensive monitoring of haemodynamics, biochemistry, coagulation and temperature is essential. A rapid infusion device is mandatory as massive blood loss may occur. All patients were electively ventilated in the surgical intensive care unit postoperatively. One patient died 11 days postoperatively. The remainder are well at the time of writing. PMID- 1509337 TI - AIDS--the Baragwanath experience. Part II. HIV infection in pregnancy and childhood. AB - By the end of 1990, 51 symptomatic children with perinatally acquired HIV infection had been admitted to Baragwanath Hospital. Of 42 children who were followed up for at least 3 months, 15 (35.7%) died and 16 (38.1%) were lost to follow-up. The case fatality rate for these children lies between 35.7% and 73.8%. Most children became symptomatic before the age of 6 months and presenting features seen in over 70% of cases included lymphadenopathy, failure to thrive and hepatomegaly. Surviving children had recurrent admissions to hospital, predominantly for respiratory distress. Many had bacterial pneumonias. Cardiac involvement (cardiomyopathy and cor pulmonale), recurrent serious bacterial infections and neurodevelopmental abnormalities were common. Our experience confirms that vertically acquired HIV infection has a relatively short incubation period and progresses rapidly with cardiorespiratory symptoms predominating. Five HIV seroprevalence studies have been conducted in pregnant women attending Baragwanath Hospital and the Soweto clinics since 1988. The calculated doubling time is between 7 and 21 months. At the end of 1990 the HIV seroprevalence rate in pregnant women was 0.82% (95% confidence limits 0.44-1.19%). PMID- 1509338 TI - AIDS--the Baragwanath experience. Part III. HIV infection in adults at Baragwanath Hospital. AB - By December 1990, 181 HIV-positive black adults had been seen in the medical wards and HIV clinic at Baragwanath Hospital. Fifty per cent were in the late stage of HIV infection; 34% of those so diagnosed in 1990 have died. Equal numbers of both sexes have been seen. Their ages have ranged from 16 years to 66 years, with peak frequencies in women aged 20-29 years and in men aged 30-39 years. Tuberculosis was the commonest complicating infection, followed by acute pneumonia. Pneumocystis carinii pneumonia was rare. Herpes zoster was the first sign of HIV infection in 13% of clinic patients. 'Slim disease' occurred in only 11% of patients, a much lower figure than in other parts of Africa. PMID- 1509339 TI - AIDS--the Baragwanath experience. Part IV. Counselling and ethical issues. AB - This fourth part of the series describes the setting up of counselling for HIV positive patients in response to the need at Baragwanath Hospital. Nurse counsellors were trained and supervised. The work, extending over 2 1/2 years, raised a number of issues for patient care and also for wider community education. Brief reference is made to pertinent ethical and cultural issues. PMID- 1509340 TI - Intracranial cryosurgery in a canine model: a pilot study. AB - Although virtually abandoned decades ago following the introduction of levodopa for the treatment of movement disorders, intracranial cryosurgery potentially offers a simple and accurate means of destroying deep-seated lesions when coupled with computed tomographic-stereotaxic placement techniques. We performed a pilot investigation of the size and histology of brain cryolesions in six dogs, using a 3-mm probe maintained at -160 degrees C for 6 minutes while simiultaneously monitoring the process by real-time ultrasound. Lesion diameter was 1.4 +/- 0.1 cm at less than or equal to 2 days but enlarged to 2.25 +/- 0.21 cm at 1 week, primarily at the expense of white matter. Ultrasound appearance of the lesion was characterized by a hyperechoic ice ball, the size of which consistently underestimated true size (determined by histology). By microscopy, the lesion was a hemorrhagic infarction that incited little surrounding edema and exhibited a sharp transitional zone. These data indicate that the cryosurgical probe can lesion significant volumes of brain in a reproducible and discrete fashion with minimal reaction to the surrounding tissue. Further work is required to clarify the observed "growth" of lesion size between days 2 and 7. PMID- 1509341 TI - Suprasellar xanthomatous Rathke's cleft cyst. AB - A case of a symptomatic suprasellar Rathke's cleft cyst in a 35-year-old woman is presented. The cyst wall and contents showed large collections of xanthomatous cells. With the exception of a few pituitary hormone-positive cells, immunohistochemical and ultrastructural features of the lining epithelium in this case of Rathke's cleft cyst were indistinguishable from colloid cysts of the third ventricle with similar secondary changes. PMID- 1509342 TI - Use of allopurinol and deferoxamine in cellular protection during ischemia. AB - During cellular ischemia and death, many changes occur in the cell. These include the build-up of purines and lipid peroxidation. In this study, we evaluated the effectiveness of allopurinol, which blocks purine breakdown, and deferoxamine, which inhibits lipid peroxidation, as cytoprotective agents. Rats were subjected to middle cerebral artery occlusion and were treated with high or low doses of allopurinol or high or low doses of deferoxamine, with normal saline used as a control. Treatments were given 1 hour before, 1 hour after, or 5 hours after occlusion. The outcome was based on neurological status and infarct size. Both infarct size and neurological status were found to be improved in all treatment groups when compared to controls. This study suggests that the use of these agents prevents cellular damage during ischemia. PMID- 1509344 TI - Multiple intracerebral arteriovenous malformations: report of three cases and review of the literature. AB - Multiple intracerebral arteriovenous malformations are thought to be exceedingly rare lesions and have usually been reported as single cases. During the past 2 years, we have treated three patients with multiple cerebral arteriovenous malformations, representing 3.2% of a consecutive series of 95 arteriovenous malformation patients seen since 1976. Details on 17 other cases are available in the literature and are summarized here. The incidence of multiple arteriovenous malformations in major series ranges from 0.3% to 3.2%; the average incidence is 1.9% based on 21 cases encountered in a total population of 1102 arteriovenous malformation patients. Patients with multiple arteriovenous malformations often have other vascular anomalies of the brain or soft tissues, but the clinical mode of presentation, age, sex, and anatomical distribution of the lesions are the same as those of patients with single arteriovenous malformations. The use of four-vessel angiography in combination with magnetic resonance imaging may result in a higher detection rate for such cases. PMID- 1509343 TI - Intracranial germ-cell tumor with synchronous lesions in the pineal and suprasellar regions: report of six cases and review of the literature. AB - The features of intracranial germ-cell tumor with synchronous lesions in the pineal and suprasellar regions (GCTSPS) in six patients were investigated. GCTSPS accounted for 12.8% of all germ-cell tumors (GCT) in our brain tumor study group. In all cases, the initial symptoms were attributable to the suprasellar lesion, and symptoms due to the pineal GCT developed only after admission. Five of the six cases were histologically diagnosed as germinoma. In all cases, tumors of both regions disappeared after irradiation, resulting in no recurrence for an average of 55.3 months. Our experience and reports in the literature suggest that GCTSPS is highly sensitive to radiation in most cases, although some reports indicated that recurrence is frequent after radiation therapy alone. It is suggested that histological diagnosis in one of the GCTSPS lesions is undertaken to make a plan for the following treatment. PMID- 1509345 TI - Association of primary intraspinal meningiomas and subcutaneous meningioma of the cervical region: case report and review of literature. AB - A report is made of a unique combination of occurrences of primary intraspinal epidural and subdural meningiomas and primary subcutaneous meningioma in the cervical region of a 15-year-old boy. The subcutaneous meningioma was detected at birth. Review of 92 recorded cases of primary dermal meningiomas revealed that they tended to occur in young patients, with an average age of 34 years for both sexes. The female-to-male ratio was 4:5. Most cutaneous meningiomas occurred in the head and neck, and the scalp was the most common site. PMID- 1509346 TI - Unexpected movement disorders in neurosurgical practice: report of three cases. AB - Hyperkinetic movement disorders may develop as a complication of stereotactic thalamotomy or pallidotomy. However, such movement disorders are uncommon after nonsterotactic intracranial operations. The authors report three cases of involuntary movement disorders unexpectedly developing after intracranial operations. The patients had undergone clipping of an internal carotid aneurysm, removal of an intracerebral hematoma, and resection of a tentorial meningioma. Two patients developed choreic movements and a dystonic posture of the unilateral upper extremity. One patient showed a tremor that had features of both parkinsonism and essential tremor. The symptoms of these patients were medically uncontrollable, and they were successfully treated with stereotactic ventrolateral thalamotomy. PMID- 1509347 TI - Central neurocytoma presenting with gigantism: case report. AB - We report a case of central neurocytoma presenting with gigantism. The patient was a 19-year-old man with a 2-year history of rapid growth. Computed tomography revealed a round, slightly enhancing calcified tumor in the septal region. This lesion was resected, and postoperative radiotherapy was given. The preoperative serum growth hormone level was 20.7 ng/mL, and postoperatively this fell to 0.9 ng/mL. Pituitary dysfunction was not noted either before or after the operation. A low level of production of growth hormone releasing factor was detected when tumor cells obtained during surgery were cultured. PMID- 1509348 TI - Aspergillotic aneurysm formation of cerebral artery following neurosurgical operation. AB - A rare case of intracranial aspergillotic aneurysm following neurosurgical operation for facial spasm is presented. Severe meningitis had persisted several days prior to the subarachnoid hemorrhage which occurred on 70th postoperative day. Angiography demonstrated a fusiform aneurysm at the peduncular segment of the superior cerebellar artery on the other side of operation. As the repeated cultures of CSF were negative, the pathogenetic factor causing aneurysm formation could not be identified before second operation of aneurysmal resection. Pathological study of the specimen revealed the arterial wall being deeply invaded by aspergillotic hyphae. PMID- 1509349 TI - Traumatic occipital condyle fracture, multiple cranial nerve palsies, and torticollis: a case report and review of the literature. AB - A 32-year-old man sustained a unique combination of injuries: an occipital condyle fracture, left tenth to twelfth cranial nerve palsies, and chronic torticollis secondary to atlantoaxial rotatory fixation. Computed tomography (CT) demonstrated a triangular fragment of bone in the posterior fossa, and three dimensional CT-reconstructed images confirmed the bone fragment to be from the occipital condyle. The patient made a good recovery with conservative management. Few occipital condyle fractures have been reported, and they should be suspected in patients who sustain painful neck and lower cranial nerve palsy following trauma. CT and plain films are complementary in confirming the diagnosis. PMID- 1509350 TI - Management of syringomyelia associated with Chiari malformation: comparative study of syrinx size and symptoms by magnetic resonance imaging. PMID- 1509351 TI - The use of anterior caspar plate fixation in acute cervical spine injury. PMID- 1509352 TI - Superselective embolization of spinal arteriovenous malformations using the Tracker catheter. AB - Eighteen patients with spinal arteriovenous malformations had been treated with conventional embolization, surgical removal, feeder ligation, and/or feeder coagulation between February 1985 and March 1990. The lesions included six glomus, four juvenile, three extramedullary, and five dural arteriovenous malformations or fistulas. Embolic therapy was conducted in 14 patients by introducing the tip of a catheter into the segmental arteries and injecting polyvinyl alcohol strips (500-1000 microns) (conventional embolization). Follow up spinal angiography disclosed recanalization in 10 patients (71.4%) and the appearance of new feeding arteries in five patients (35.7%). We introduced the Tracker vascular access system in April 1990. Eight patients (four glomus, one juvenile, and three dural arteriovenous malformations) were treated with the minicatheter and Ivalon particles (150-350 microns). Five patients showed neurological improvement immediately after treatment. The other three patients had severe paraparesis before treatment and did not show any improvement. One patient with a glomus-type arteriovenous malformation showed transient neurological deterioration just after embolization with the Tracker-10 to occlude a lesion fed by the posterior spinal artery, because the Ivalon particles migrated into the anterior spinal artery via the anterior spinal canal artery. In one patient with a juvenile arteriovenous malformation, the Tracker-18 catheter perforated the radiculomedullary artery originating from the right vertebral artery, and subarachnoid hemorrhage occurred. However, the Tracker-10 could later successfully occlude the arteriovenous malformation. The rates of recanalization and appearance of the new feeding vessels were 4/8 (50.0%) and 2/8 (25%), respectively. PMID- 1509353 TI - Long-term follow-up of radiosurgically treated arteriovenous malformations in children: report of nine cases. AB - Long-term follow-up results of nine children treated for cerebral arteriovenous malformation with a gamma unit are presented. Complete nidus obliteration was angiographically confirmed in six cases and significant decreases in arteriovenous malformation size were observed in the other three. There were no radiation-related deteriorations in physical or mental development. In seven patients who underwent endocrinological examination more than 3 years after irradiation, five were normal and the other two showed only low serum adrenocorticotropic hormone levels, which, however, did not necessitate replacement therapy. Neurodiagnostic imaging follow-up studies revealed no radiation-induced lesions in any of the nine cases. PMID- 1509354 TI - Fundus hemorrhages in infancy. AB - The anatomical location and appearance of retinal hemorrhages in the infant provide important clues in the diagnosis of underlying disorders. While neonatal retinal hemorrhages related to birth trauma are common, benign, and self-limited, other retinal hemorrhages in infancy may signify intracranial aneurysms, accidental or non-accidental injury, and a variety of ocular (e.g., Coats' disease, PHPV, ROP, retinal dysplasia, hypertension, myopia) or systemic disease (e.g., hematologic or cardiovascular disorders, infection, protein C deficiency). In this review, retinal hemorrhages are illustrated and classified according to location, appearance, and etiology. Prompt diagnosis of retinal hemorrhages in infants is crucial, because treatment may be required to prevent early deprivation amblyopia and blindness. Ophthalmological findings may also be a valuable contribution to the overall medical evaluation of the infant. PMID- 1509355 TI - Recognizing and managing the litigious patient. AB - There is no accurate pre-treatment profile of the litigious patient. It is usually the lawsuit-causing physician who drives the patient to initiate litigation. The establishment and control of the physician-patient relationship are the keys to preventing litigation; this is achieved by improving physicians' ability to communicate, demonstrate empathy and support, and conduct appropriate discussion of informed consent. After treatment, physicians must pay special attention to patients who exhibit certain behavior typical of dissatisfaction. They should be accorded extra time and attention and, in some instances, should be referred to another practitioner for a second opinion and follow-up care. PMID- 1509356 TI - Sudden visual loss with slow recovery. AB - A 58-year-old healthy man presented with a history of monocular visual loss with incomplete recovery. The differential diagnosis, evaluation, and possible therapeutic interventions are discussed. The presenter controversially felt that although the source of embolic material was likely ipsilateral carotid artery and no evaluation was necessary. PMID- 1509357 TI - Theodor Leber: a founder of ophthalmic research. AB - Theodor Leber became famous for his dissertation on the ocular circulation in 1865 at the youthful age of twenty-five. He was Professor of Ophthalmology at Goettingen between 1870 and 1890 and at Heidelberg University between 1890 and 1910. By presenting his original descriptions of the disorders that bear his name, this article commemorates the death, seventy-five years ago, of a founder of ophthalmic research. PMID- 1509358 TI - [The role of immune complexes in chronic liver diseases and their dynamics during treatment]. AB - Chronic liver diseases are marked by a well-defined relationship between the intensity of the cytolytic syndrome and the level of circulating immune complexes (CIC). The highest damaging action on hepatocytes is produced by medium-sized CIC because of their penetrating and complement fixing effects. The level of thrombocytopenia and, to a less measure, of leukopenia also depends on the concentration and size of CIC in CAH and liver cirrhosis (LC), which may provide indirect evidence of the lytic action of CIC on hepatocytes, leading in turn to the impairment of microcirculation and aggravation of hepatocyte hypoxia. The data obtained attest to the role CIC of varying size play in the pathogenesis of CAH and LC. The changes in the properties of immune complexes induced by the derangement of cellular membranes also influence the course of immune responses, favouring an increase of antibody formation. As a result of an appreciable suppression of antibody and medium-sized CIC formation enhancing the cytolytic syndrome, the preference during glucocorticoid treatment should be given to the use of the medium doses of prednisolone which ensure less intensity and less duration of cytolysis as compared to the application of large drug doses. PMID- 1509359 TI - [The importance of immunogenetic studies in Itsenko-Cushing disease combined with other endocrine diseases]. AB - Ninety-seven patients suffering from Itsenko [correction of Icenko]-Cushing disease were examined. Analysis was made first of all of the clinical and laboratory signs pointing to the presence of other endocrine diseases to distinguish two groups of patients. The first group included subjects who did not manifest any concomitant diseases. The number of men and women was the same. The second group was made up of patients with associated Itsenko [correction of Icenko]-Cushing disease and other endocrine diseases. In this particular group, women were predominant. The first group patients demonstrated the predominance of the DR7 incidence, the second group that of the DR5. The method of estimating HLA associations identified is proposed. It allows distinguishing specific and nonspecific associations. In Itsenko [correction of Icenko]-Cushing disease, DR7 association is specific, whereas B8 and DR5 associations are unspecific. A specific polyendocrine autoimmune syndrome associated with Itsenko [correction of Icenko]-Cushing disease was revealed. A concept of the pathogenesis of Itsenko [correction of Icenko]-Cushing disease is advanced. PMID- 1509360 TI - [The characteristics of the clinical course of lymphosarcomas when using combined therapy including splenectomy]. AB - The authors relate the results of a clinico-morpho-instrumental analysis of the clinical course of lymphosarcomas in 38 patients with different morphological patterns of the disease with primary injury to the spleen. The patients received multimodality therapy including splenectomy. It has been established that later the short-term effect of splenectomy permits the implementation of different polychemotherapy programs, favouring a better lymphosarcoma prediction. PMID- 1509361 TI - [The metabolic effects of glucocorticosteroids in patients with chronic obstructive bronchitis]. AB - The purpose of the study was to examine the effect of glucocorticosteroids on metabolic processes that occur in alveolar macrophages and bronchoalveolar liquid in patients with chronic obstructive bronchitis, in particular the activity of the antioxidant defense system, processes of hydrogen peroxide generation, and the content of phospholipids. It has been discovered that in patients suffering from chronic obstructive bronchitis, glucocorticosteroids suppress hydrogen peroxide production and exert a negligible effect on the antioxidant system of alveolar macrophages as well as stimulate the synthesis of phospholipids in pulmonary tissue and suppress phospholipase A2 activity. To prevent unfavourable metabolic effects of glucocorticosteroids, antioxidants and stimulants of phagocytosis can be applied. PMID- 1509362 TI - [The characteristics of the formation of territorial differences in population mortality]. PMID- 1509363 TI - [Peptic ulcer combined with other pathology. The clinical manifestations, course and therapy]. AB - The author describes and classifies the most frequently occurring combinations of peptic ulcer and pathology of other organs and systems on the basis of examining more than 2,000 patients. Diseases and syndromes associated with peptic ulcer are distributed into 2 groups: within the gastrointestinal tract and outside it. The former ones include cardia insufficiency, deranged bowel function, rectal syndrome, diseases of the gallbladder, pathology of the liver and pancreas; among the latter ones are essential hypertension, atherosclerosis, coronary heart disease, chronic nonspecific pulmonary diseases, and diabetes mellitus. Different pathogenetic relations and clinical load are shown to exist between the underlying disease and concomitant illnesses. Evidence is provided for the concept of enlarged spasms (phenomenon of the spastic dominant) common to peptic ulcer. Efficient methods of the individualized treatment of patients with concomitant pathology are described. PMID- 1509364 TI - [The diagnosis of cancer of the stomach and large intestine under active dispensary observation]. AB - Among patients placed under permanent medical observation carried out for 6-8 years, gastric carcinoma (GC) was revealed in 288 and colonic carcinoma (CC) in 377 cases. In 67 and 60% of the patients, respectively, the diagnosis was established as a result of systematic dispensary examinations. The first and second stage disease was identified in 50 and 43% of the cases, including 67% of GC and 62% of CC patients undergoing active examinations. In 40% of the cases on the average, the disease may run an asymptomatic course, including the late stages of the disease. In half the patients, the clinical manifestations did not last more than 3 months, with their duration being independent of the disease stage. It is assumed that at the initial stage the tumor may, during a short period of time, reach the size corresponding to both early and late stages of the disease, after which the rate of tumor growth is likely to be slower. The authors document the necessity of a comprehensive approach to the diagnosis of GC and CC, using the whole armamentarium of classical and up-to-date methods. PMID- 1509365 TI - [Diaphragmatic-inspiratory palpation of the liver and right kidney]. PMID- 1509366 TI - [The validation of the diagnosis and the successful treatment of celiac disease in adults]. PMID- 1509367 TI - [A case of systemic mastocytosis in therapeutic practice]. PMID- 1509368 TI - [The role of vascular pathology in the pathogenesis of peptic ulcer]. PMID- 1509369 TI - [The pathogenesis of reflux gastritis]. PMID- 1509370 TI - [Chronic primary gastroduodenitis]. PMID- 1509371 TI - [Lead-induced colic. New data and views]. PMID- 1509372 TI - [Heat-shock proteins: their role in physiological and pathological processes]. PMID- 1509373 TI - [Unconjugated hyperbilirubinemia in young people]. AB - Altogether 64 young patients with nonconjugated hyperbilirubinemia (NH) underwent clinico-morphological correlations to establish the nosological essence of pigment metabolism disorders revealed. 32 patients showed up the signs of chronic nonspecific hepatitis, including 7 patients with the signs of chronic aggressive hepatitis. The remainder 15 patients were found to have other inflammatory processes in the liver. Only 10 persons examined (15.6%) were diagnosed to have functional hyperbilirubinemia and 7 (10.9%) to have latent hemolytic anemia. The conclusion is made about the necessity of a comprehensive examination of young persons with NH. The morphological examination of the liver is a must to early verify the pathological process manifested by the impairment of pigment metabolism. PMID- 1509374 TI - [The clinical significance of immunodeficiency states in patients with viral hepatitis B]. AB - Examination of 374 patients with acute viral hepatitis B made it possible to unravel certain mechanisms of the development of secondary immunodeficiency in the T immunity system: hypoxia and hypoxemia, activation of lipid peroxidation, suppression of antioxidant activity of blood serum, derangement of the synthesis of free radical forms of oxygen by mono- and polynuclear cells and ATR deficiency in them, disturbance of the interferonogenesis and synthesis of cyclic nucleotides, suppression of metabolic activity of immunocompetent cells. The character and intensity of immunodeficiency states underlie the formation of different clinical forms of viral hepatitis B. PMID- 1509375 TI - [Laser flow cytometry in the diagnosis of chronic hepatitis of different etiologies]. AB - A study was made of the immune status in patients suffering from chronic hepatitis (CH) of viral, alcoholic and toxic etiology. The T-system cellular immunity (OKT-3+, OKT-4+, OKT-8+, OKT-11+) was subjected to a subpopulation analysis using monoclonal antibodies and flow laser cytometry. CH of varying etiology is marked by impairment of the immune status. Especially manifest are suppression of OKT-3(+)-, OKT-4(+)-, OKT-8(+)-positive cells and imbalance of OKT 4+ and OKT-8+, with the changes revealed being dependent on the etiological pattern of CH. The data obtained point to the development of secondary immunodeficiency of the T-cell component at the level of different T lymphocyte subpopulations, which depends on the clinico-morphological and etiological pattern of CH. The revealed changes in the immune system may serve as a criterion for differential diagnosis and elaboration of efficient immunocorrective therapy of CH. PMID- 1509376 TI - [The immunomodulating and hepatotropic effect of correcting hyperprolactinemia and hypophyseal gonadotropic dysfunction in liver cirrhosis patients]. AB - Men suffering from liver cirrhosis were examined. They demonstrated a decrease in the blood content of gonadotropic hormones and testosterone and a rise of estradiol and prolactin. The changes indicated were more pronounced in decompensated liver cirrhosis and were associated with lipid peroxidation activation and a reduction of the count of T suppressor lymphocytes. As a result, the treatment of men suffering from decompensated liver cirrhosis and hyperprolactinemia by parlodel lowered blood prolactin and activity of lipid peroxidation. The use of chorionic gonadotropin for the treatment of men with decompensated liver cirrhosis and a low content of blood lutropin produces an immunomodulatory effect. Parlodel and chorionic gonadotropin favour a decrease of the cytolytic syndrome. PMID- 1509377 TI - [The immunological indices in inflammatory and tumorous diseases of the pancreas]. AB - Nineteen patients with pancreatitis and 40 with pancreatic carcinoma were examined for certain immunological characteristics (immunoglobulins, immune complexes, PHA-induced lymphocyte proliferation) and for the level of carcinoembryonic antigen (CEA) and CA 19-9 depending on blood bilirubin. Hyperbilirubinemia was identified in 21 patients with carcinoma and in 3 suffering from pancreatitis. Both patients' groups manifested an increase of the IgA level. Especially high characteristics were seen in hyperbilirubinemia. The level of other class immunoglobulins and immune complexes did not depend on blood bilirubin. The patients demonstrated suppression of PHA-induced lymphocyte response by autologous plasma, with more remarkable suppression being observable in hyperbilirubinemia. The level of CEA or CA 19-9 was increased in 89% of the patients with pancreatic carcinoma and in 30% of pancreatitis patients. No relationship was recorded between the level of oncofetal antigens and blood bilirubin. PMID- 1509378 TI - [Cholecystokinin incretion and the pharmacological effects on it in patients with chronic pancreatitis]. AB - In patients with chronic pancreatitis (CP) (cholepancreatitis and primary recurrent pancreatitis), a moderate decrease of urocholecystokinin (UCK) excretion as a criterion for incretion of cholecystokinin-pancreozymin (CK) by duodenal endocrine cells was recorded in the presence of concomitant atrophic duodenitis. The beta-adrenoblocker obsidan, the blocker of m-cholinergic receptors gastrozepin, the antagonist of calcium channels finoptin and the synthetic analog of endogenous opiates dalargin reduced excretion of UCK in CP exacerbation. The decrease of CK incretion can be viewed as one of the mechanisms of the therapeutic action of these drugs in CP exacerbations. In the stage of CP remission, calcium gluconate consistently increased basal and intraduodenal oil (as a realizer of CK incretion) infusion-stimulated excretion of UCK. The enhancement of duodenal incretory activity is an essential mediating mechanism by which calcium gluconate stimulates pancreatic enzyme excretion. PMID- 1509379 TI - [The pathogenetic problems of gastric and duodenal peptic ulcer]. AB - Studies into the content of nonspecific defense factors, secretory and serum immunoglobulins in blood and biological fluids (saliva, gastric juice, duodenal contents) in patients suffering from peptic ulcer have demonstrated significant changes in local and general immunity. Exacerbation of the disease was marked by a decrease of the titer of complement, C3-component of complement, and lysozyme level. At the same time there was an increase of the concentration of secretory immunoglobulins and immunoglobulins in blood serum and external secretions. The data obtained attest to the tension of humoral immunity and nonspecific defense in peptic ulcer patients, giving rise to the consideration of the changes in the humoral component as one of potential mechanisms by which ulcer is formed. PMID- 1509380 TI - [The problems of modern clinical hepatology]. PMID- 1509381 TI - [The characteristics of duodenal peptic ulcer in obese persons]. AB - Analysis was made of the rate of clinical manifestations and complications in 77 patients with overweight exceeding stage I obesity, suffering from duodenal ulcer. In the overwhelming majority of the patients, the disease ran with typical complaints and the diagnosis of peptic ulcer was not difficult. In subjects prone to and suffering from obesity, duodenal ulcer accounted for 2.3% among all the patients with duodenal ulcers. The patients were noted to be fairly prone to complications, particularly to the stenosing of the duodenum. Concomitant complications occurred frequently enough (36.3%). In obese patients, nontypical "low" localization of duodenal ulcer and a high proneness to hypersecretion were encountered more frequently. PMID- 1509382 TI - [The diagnostic value of the histamine test in studying the gastric juice of patients with duodenal peptic ulcer]. AB - Measurements were made of the content of pepsin and hydrochloric acid in gastric juice from 96 duodenal ulcer patients, obtained under the conditions of basal secretion and after histamine administration in the submaximal dose. The disease was marked by changes in the response to histamine on the part of gastric glands. In duodenal ulcer patients, histamine primarily stimulates pepsin secretion whereas in healthy subjects, secretion of hydrochloric acid is predominant. Based on the regularity thus revealed, a new test (the ratio of the histamine index of pepsin to the histamine index of hydrochloric acid) was developed. This test is of importance for the diagnosis of duodenal ulcer and predicting the gravity of the course it may run. PMID- 1509383 TI - [The differentiated treatment of patients with duodenal peptic ulcer]. AB - There were 45 patients suffering from duodenal ulcer in the stage of exacerbation and 15 subjects who served as control. Radioimmunoassay and immunomorphological PAP methods were used to examine the blood PGI and gastrin levels, the number of gastroduodenal G and D cells, the characteristics of basal and stimulated acid production in gastric juice in the treatment with gastrozepin (22 persons) and ranisen (23 persons). Depending on the concentration of gastrin in the blood and the number of pyloric G cells, the patients were distributed into two groups: with hypergastrinemia and/or hyperplasia of G cells (48%) and with normogastrinemia and the normal number of these cells (52%). It has been shown that the continuous treatment with gastrozepin of the patients with hypergastrinemia and/or hyperplasia of pyloric G cells was followed by the normalization of blood gastrin concentration and of the number of pyloric G cells; on the contrary in the patients with normogastrinemia and the normal amount of these cells, the analogous characteristics remained unchanged. After the treatment with ranisan the patients with normogastrinemia and the normal amount of pyloric G cells manifested hypergastrinemia without any changes in the amount of G cells; meanwhile in the patients with hypergastrinemia and/or hyperplasia of G cells, the analogous characteristics were unchanged. In these groups patients, the rate and the times of the relapse occurrence were different throughout the whole year. The data obtained support the nonuniformity of duodenal ulcer. PMID- 1509384 TI - [The dynamics of the indices of protein metabolic homeostasis and the status of duodenal mucosal regeneration during the etaden treatment of duodenal peptic ulcer]. AB - The authors relate the results of examining 149 men suffering from duodenal ulcer. The main group was made up of 75 patients given parenteral etaden treatment combined with conventional therapy. A study was made of the dynamics of clinical manifestations, the level of total protein and its fraction in the blood, protein metabolism (by radionuclide technique). Pieces of the duodenal mucosa from the periulcerous area were examined under microscope. Scanning and electron microscopy was also performed. Based on the data obtained it is concluded that etaden had active influence on protein synthesis, which favoured more rapid regression of the ulcerous defect in the main group patients. Morphological studies have also shown the positive dynamics of the regenerative process. PMID- 1509385 TI - [The effect of hyperbaric oxygenation on the secretory, motor function and microcirculation of the stomach and duodenal walls in patients with duodenal ulcers]. AB - A total of 22 patients with duodenal ulcer were examined for secretory and motor functions, microcirculation of the gastroduodenal wall and changes in the stomach duodenum interrelations under the influence of hyperbaric oxygenation. Of these, group I included 9 patients with active ulcer; group II 13 persons with a healing ulcer. To assess gastric and duodenal functions, use was made of pH-metry combined with the measurement of intraluminal pressure by "open catheters". Microcirculation of the gastroduodenal wall was estimated by the radiation method. The studies have shown that the patients with active ulcer treated by hyperbaric oxygenation manifested a decrease of motor activity of both stomach and duodenum, an improvement of acid-neutralizing function of the stomach, a reduction of the duration of duodenum acidification, a greater normalization of microcirculation in the duodenal wall than in the gastric wall. In the patients with healing ulcers, the duodenal motility returned to normal, the initially elevated gastric motility fell to normal, the acidification of the duodenal bulb declined, and the regional blood flow returned to normal. It may thus be concluded that the positive impact of hyperbaric oxygenation on gastroduodenal function was more pronounced in the patients with healing ulcers where a more considerable decrease of motor activity was not accompanied by duodenal motility suppression. PMID- 1509386 TI - [The clinico-pathogenetic variants of cholestasis in different liver diseases]. AB - To base the clinico-pathogenetic nonuniformity of cholestasis in different liver diseases, 135 patients distributed into groups were examined. Group I was made up of 48 patients with chronic persistent hepatitis, group II of 34 patients with chronic active hepatitis, group III of 29 patients with liver cirrhosis, and group IV of 24 patients with primary and metastatic liver carcinoma. The data obtained suggest the existence of different forms of cholestasis: multicomponent cholestasis, partial bilirubin cholestasis, partial choleacid cholestasis. In the group I patients, the incidence of cholestasis was 8.3%, in group II 2.9%, in group III 3.4%. The incidence of partial choleacid cholestasis was 4.2% in group I, 2.9% in group II, and 6.9% in group III. The presence of partial cholestasis may be caused by the impairment of the assumed "personal" carrier for different bile components. PMID- 1509387 TI - [Chronic gastritis from the aspect of a thrombohemorrhagic syndrome]. AB - As many as 148 patients were examined to demonstrate that chronic gastritis (CG) runs its course in the presence of marked changes in microcirculation and hemostasis which go into the framework of the chronic recurrent thrombohemorrhagic syndrome. The manifestations of the latter one were more appreciable in a dramatic exacerbation of the disease, erosive gastritis, diffuse atrophy of the mucous membrane and secretory insufficiency of the stomach, and disease standing over 10 years. The disorders indicated are involved into the pathogenesis of CG and promote the development of morphofunctional alterations in the gastric mucosa. PMID- 1509388 TI - [Functional intestinal dyskinesias]. AB - The authors relate the results of examining 120 patients with functional disorders of the colon. The majority of the patients manifested diverse mental abnormalities of the neurotic origin, represented by different patterns of mental pathology, somatized disturbances, neuroses and psychopathies. The conditions favouring the origin of neurotic and functional disorders have been elucidated. It is concluded from the comparison of different treatment modalities that psychotherapy may be preferred. PMID- 1509389 TI - [The processes of mono-, bi- and polysubstrate digestion in chronic enteritis]. AB - Forty-six patients suffering from chronic enteritis (CE) and 34 healthy subjects were examined for the effect of standard polysubstrate food (protein plus fat plus carbohydrate). It has been shown that in the healthy subjects, addition of protein food exerted a stimulating effect on enzymic and absorption functions of the small intestine whereas fat intake produces a reverse, inhibitory effect. As a rule, in small intestinal lesions that effect is retained. However, there was a significant reduction of the hydrolysis and absorption of both monosubstrate and bi- and polysubstrate food. It should be stressed that in CE patients, the use of polysubstrate food results in its better assimilation as compared to monosubstrate food substances. PMID- 1509390 TI - [Gluten enteropathy]. AB - The authors relate the results of 10 years of observations of 113 patients suffering from gluten enteropathy (GE) of the adults. In all the patients, the diagnosis was supported by the presence of hyper-regenerative atrophy of the small intestinal mucosa (total in 70% and subtotal in 30%). Metabolic disorders and cellular immunity were investigated. At the onset of the observations 70.7% of the patients demonstrated malabsorption, stage III gravity, and 29.3% stage II. It has been proved that permanent and strict adherence to the agluten diet and administration of corticosteroids in the most severe cases in combination with pathogenetic therapy of diarrhea and metabolic disorders permit attaining a steady clinical remission, improvement of normalization of the biochemical and immunological characteristics, a tendency toward normalization of the small intestinal mucosa, and even the recovery of its normal structure in part of the cases. PMID- 1509391 TI - [The function of the small intestine based on hydrogen test data in men who have been exposed to small doses of ionizing radiation in the cleanup of the sequelae of the accident at the Chernobyl Atomic Electric Power Station]. AB - Sixty-seven participants of the elimination of Chernobyl accident sequels were examined. Of these, 30 persons (44.8%) showed normal characteristics of the three small intestinal functions studied: activity of the intestinal enzyme beta galactosidase, motility and microbial dissemination, 23 (34.3%) deficiency of the intestinal enzyme beta-galactosidase, and 24 (35.8%) bacterial dissemination of the small intestine. In 12 persons (17.9%), the deficiency of beta-galactosidase was associated with dysbiosis of the small intestine. The incidence of hypolactasia did not exceed the characteristic typical on the whole of the population of the Moscow region. PMID- 1509392 TI - [Errors in the diagnosis of diseases of the large intestine]. AB - The quality of the diagnosis of colonic diseases was analyzed in 395 patients. Comparisons were made of the diagnoses on admission to and discharge from hospital: in irritated colon and its dyskinesias, ulcerous colitis and Crohn's disease, carcinoma, polyps, other forms of colitis and so forth. Errors in the basic diagnosis constituted 51.0 +/- 1.8%; including 25.4 +/- 1.6% of cases of overdiagnoses; in 25.6 +/- 1.6%, the disease was not recognized. The main colonic diseases were coupled with other intestinal diseases in 42.3 +/- 2.5%, with other diseases of the alimentary organs in 37.2 +/- 2.5% of cases. The quality of the diagnosis is affected by wrong medical thinking, insufficient application of colonoscopy as well as polymorbidity of modern patients, growing with their age. Approaches to the improvement of the quality of the diagnosis of colonic diseases are determined by the causes and mechanisms of the errors made. PMID- 1509393 TI - [Destabilization of the immune homeostasis in patients with nonspecific ulcerative colitis of varying degrees of severity]. AB - As a result of evaluating immune homeostasis in patients suffering from nonspecific ulcerous colitis, the predictors of the patient's gravity have been established. They include: 1) phagocytic activity; 2) changes in bioenergetic processes of the cells; 3) redistribution of functional activity and its phenotypic expression among lymphocytes; 4) imbalance of humoral factors of immunity; 5) augmentation of anemia with decreased or increased iron content. PMID- 1509394 TI - [The possibilities for the early diagnosis of ankylosing spondylarthritis]. AB - Soluble antigen HLA-B27 was assayed in blood serum of 30 patients afflicted with ankylosing spondyloarthritis (AS) and 25 healthy subjects having HLA-B27 (B27+) antigen in the phenotype. As compared to B27+ healthy subjects, B27+ patients with AS demonstrated a significantly higher level of soluble HLA-B27 antigen. A substance whose functional activity was found to be identical to that of soluble HLA-B27 antigen in blood serum of B27- patients with AS was discovered for the first time. It was absent from B27- healthy subjects. In addition to the identification of the fixed forms of soluble HLA-B27 antigen, the assay of this antigen in blood serum enhances the potentialities of laboratory diagnosis of AS, which plays an important role at the early disease stages. PMID- 1509395 TI - [The use of radiothermometry in patients with rheumatoid arthritis]. AB - As a result of the work carried out, one could decide some problems: to develop standardized points of measuring temperatures of the deep structures of the joints using radiothermography, to establish for the first time the normal radiothermographic values of the temperatures for different joint groups, to recommend radiothermography as an adjuvant method for revealing early signs of the activity of rheumatoid arthritis (RA) associated with OA. Radiothermography is a convenient, cheap, available and an informative enough method, fit for the use in clinical practice to improve the diagnosis and treatment of RA. PMID- 1509396 TI - [The metabolic characteristics of nonesterified fatty acids in the myocardium of patients with paroxysmal tachycardias and their pathogenetic role in the origin of the heart rhythm disorders]. AB - Twenty-one patients suffering from paroxysmal tachycardia (PT) were examined for metabolism of nonesterified fatty acids (NEFA) in the myocardium as well as for interrelations with the parameters of clinical electrophysiology. It has been shown that the main features of NEFA metabolism in the myocardium of RT patients lie in their high concentration in arterial blood and in the blood of the coronary heart sinus and in their high ratio of extraction by the myocardium both in the presence of sinus rhythm and during RT, which is of the pathogenetic importance in the origin of heart rhythm disturbances. NEFA exert different effects on the antegrade and retrograde (functional and effective) refractory periods of different parts of the conduction system of the heart, favouring the onset of their electrophysiological heterogeneity. PMID- 1509397 TI - The structure and function of von Willebrand factor. PMID- 1509398 TI - Prevalence of inhibitors in a population of 3435 hemophilia patients in France. French Hemophilia Study Group. AB - A cooperative study between the 37 centers of the French Hemophilia Study Group was undertaken to establish the prevalence of inhibitor patients in the French hemophilia population. The prevalence reported in the literature varies widely from 3.6% to 17.5%. Some of the studies are dealing with a small number of patients and inhibitor patients are reported either to the total number of hemophiliacs or to the severely affected ones. The French study provided information concerning 3,435 hemophiliacs and showed a prevalence of 6.2% for the overall population. Prevalence of inhibitors was found to be 7% in the population of hemophilia A patients and 12.8% in the population of severely affected ones. The prevalence of inhibitors in the population of hemophilia patients was 2% and 4% in the population of severely affected hemophilia B patients. The cooperative study also showed that 47.5% of inhibitors are detected before 10 years of age and that 82% of inhibitor patients are high responders. Analysis of inhibitor detection in patients under the age often showed that there was a peak in the population of 2 years old children. Although not comparable to the present study the high incidence of inhibitors with ultrapurified and recombinant FVIII reported in previously untransfused patient may be borne in mind. PMID- 1509399 TI - Value of liquid crystal contact thermography and plasma level of D-dimer for screening of deep venous thrombosis following general abdominal surgery. AB - Because the use of radioactive fibrinogen uptake test (FUT) has become questionable both for ethical (risk of virus transmission) and technical (lack of sensitivity) reasons, we investigated the potential value of two alternative methods for screening of asymptomatic deep venous thrombosis following elective digestive surgery: liquid crystal contact thermography (LCCT) and measurement of plasma concentration of D-dimer (DD), as compared with bilateral ascending phlebography. Out of 194 patients, 185 underwent phlebography on the 8th (0-19, median and range) postoperative day. Despite prophylaxis with low-molecular weight heparin and elastic stockings, DVT was detected on phlebography in 58 legs of 45 patients. Sensitivity of LCCT with respect to the presence of DVT was 55% (n = 184 patients) or 28% (n = 368 legs) with a specificity of 67% and 82%, respectively. These poor performances were obtained despite a good interobserver agreement for the LCCT assessments (overall kappa coefficient of 0.66 between three experts). The most accurate cut-off of DD for discriminating patients with or without DVT was 3,000 micrograms/l, as determined by ROC curve analysis. Sensitivity of a DD level of more than 3,000 micrograms/l for the presence of phlebographically documented DVT on the 8th postoperative day was 89% for a specificity of 48%. Thus, LCCT cannot be used for screening of postoperative, mainly asymptomatic DVT following general surgery. On the other hand, measurement of plasma DD may be useful for initial screening, a negative result (level less than 3,000 micrograms/l) allowing to exclude DVT (negative predictive value of 93%) and a positive result (positive predictive value of 35%) requiring confirmation by phlebography.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1509400 TI - Thrombospondin levels in patients with malignancy. AB - Thrombospondin (TSP), a large glycoprotein present in platelets, and various normal and tumor tissues, has recently been shown to promote cell adhesion and platelet aggregation. Most importantly because TSP has been shown to promote metastasis of melanoma tumor cells to the lung in a murine model (1) and since thromboembolic events commonly occur in patients afflicted with metastatic tumors, we explored the role of TSP in human cancer by measuring TSP blood levels in patients with various malignant neoplasms. Blood TSP levels were measured by indirect enzyme-linked immunoadsorbent assay (ELISA) from 20 control subjects, 22 patients with gastrointestinal (GI) cancer, 18 patients with breast cancer, and 17 patients with lung cancer. Control subjects consisted both of healthy subjects and acutely ill patients with no malignancies. TSP levels of both healthy and acutely ill controls were found to range between 245-440 ng/ml with a mean of 365 ng/ml. In contrast, elevated levels of TSP greater than the mean value of 400 ng/ml for controls ranging between 590-3,650 ng/ml were found in 20/22 (91%) patients with GI malignancies, 13/18 (72%) patients with breast cancer, and 15/17 (88%) with lung cancer. Mean TSP levels of GI, breast, and lung cancer patients were 3, 2, and 3 fold greater than controls, respectively. Increased blood TSP levels in patients were not due to increased levels of platelets since both control and patient groups had platelet counts within the normal range. These results suggest that TSP may play a role in tumor cell metastasis in man and could serve as a blood marker for metastasis. PMID- 1509401 TI - Tumor necrosis factor induces von Willebrand factor release in healthy humans. AB - Tumor necrosis factor (TNF) is an important mediator of the host responses to systemic infection. To investigate the effect of TNF on the release of von Willebrand factor (vWF) into the circulation, we performed a controlled study in six healthy men, sequentially measuring the plasma concentrations of vWF antigen after a bolus intravenous injection of recombinant human TNF (50 micrograms/m2). TNF induced a marked increase in vWF antigen plasma levels, becoming significant after 45 min and peaking after 4 h (percentage increase from base line: 351 +/- 46; p less than 0.0001, TNF versus saline). The multimeric organization of circulating vWF was not affected by TNF. We conclude that TNF may be an early mediator of increased vWF secretion in systemic infection. PMID- 1509402 TI - Heparin binding to plasma proteins, an important mechanism for heparin resistance. AB - Heparin dosage requirements vary widely among patients with venous thromboembolism. In this study, we measured the proportion of anticoagulantly active heparin which was reversibly bound and neutralized by plasma proteins (defined as reversible heparin neutralization) in the pre-treatment plasma (in vitro) and in the 6 h post-treatment plasma (ex vivo) of patients with venous thromboembolism treated with a fixed dose of heparin. Reversible heparin neutralization was assessed by comparing the heparin levels measured as anti factor Xa activity before and after the addition of low affinity heparin which is essentially devoid of anti-factor Xa activity, in order to displace heparin bound to plasma proteins. The results indicate that reversible heparin neutralization due to binding to plasma proteins is a major determinant of the anticoagulant response to a fixed dose of standard heparin 6 h post-treatment and of the eventual heparin dose required to achieve a therapeutic anticoagulant effect on days 3-5 of heparin treatment. PMID- 1509403 TI - A novel sensitive assay for functional factor XII based on the generation of kallikrein-C1-inhibitor complexes in factor XII-deficient plasma by glass-bound factor XII. AB - We developed a very sensitive assay for functional factor XII. This assay is based on the property of glass-bound factor XII to activate prekallikrein (PK) into kallikrein in factor XII-deficient plasma, which is assessed by measuring the formation of kallikrein-C1-inhibitor complexes in this plasma by radioimmunoassay. Incubation of varying amounts of factor XII in glass tubes led to a dose-dependent increase in kallikrein-C1-inhibitor complexes in factor XII deficient plasma with a lower limit of detection of +/- 20 pg of factor XII. The specificity of the assay for factor XII was demonstrated by experiments with plasmas deficient for factor XII, PK or high molecular weight kininogen (HK) and by incubation of factor XII with Polybrene or with a monoclonal antibody that inhibits the amidolytic and procoagulant activity of factor XII. The high sensitivity of the assay appeared to be due to the inability of C1-inhibitor to inhibit factor XII bound to glass, which resulted in a molar ratio of generated kallikrein to glass-bound factor XII of at least 100:1. This assay for factor XII may be a feasible tool in studies on structural and functional aspects of (recombinant) factor XII species synthesized by cultured cells. PMID- 1509404 TI - Beta 2-glycoprotein I deficiency and the risk of thrombosis. AB - beta 2-glycoprotein I (beta 2-GP I) is a plasma protein with a high affinity for negatively charged surfaces. In vitro this protein shows a variety of anticoagulant properties (inhibition of contact activation and platelet dependent prothrombinase activity). Therefore we studied the possibility that a hereditary beta 2-GP I deficiency is a risk factor for (familial) thrombophilia. Plasma beta 2-GP I levels were measured in healthy volunteers and four different groups of patients with (familial) thrombophilia. In these 5 groups the prevalence of beta 2-GP I deficiency (i.e. beta 2-GP I antigen less than 77%) was found to be very similar (6.8-12.5%) and statistically not significantly different. This observation suggests that beta 2-GP I deficiency in itself is not a risk factor for thrombosis. One thrombophilic patient was found to be homozygous deficient of beta 2-GP I. The transmission of the defect in his family followed autosomal inheritance. One of his brothers was also homozygous deficient and at the age of 35 years still free of thromboembolic complications. The possibility that beta 2 GP I deficiency could be an additional risk factor for the development of thrombophilia in families with protein C deficiency was evaluated in a panel of 70 unrelated patients with clinically dominant protein C deficiency. The prevalence of beta 2-GP I deficiency in this group of patients (12.8%) was very similar to that in other groups of normals and patients. Moreover, there was no difference in the frequency of beta 2-GP I deficiency in symptomatic and asymptomatic protein C deficient patients. PMID- 1509405 TI - Factor VIIa/tissue factor-catalyzed activation of factors IX and X on a cell surface and in suspension: a kinetic study. AB - The kinetics of activation of factor IX and factor X by factor VIIa was studied in the presence of various sources of tissue factor: (1) a surface membrane of human ovarian carcinoma cell line, OC-2008 (2) the cell lysate (of OC-2008) and (3) reconstituted purified human tissue factor. The rates of activation of factors IX and X were monitored in activation peptide release assays using tritiated substrates. The results indicate that the apparent Km values for factor IX and factor X were similar for a given tissue factor, but varied with tissue factor source. The source of tissue factor greatly influenced the apparent differences in Vmax for factors IX and X. When a surface of monolayer provided tissue factor, the Vmax of factor IX was only 2-3 fold lower than factor X, but when either a cell lysate or purified tissue factor was the source of cofactor activity, the difference in Vmax rose to about 8-10 fold. Although, the tissue factor apoprotein in the cells was expressed entirely on the outer surface membrane, the activity of tissue factor on the intact cell surface was 50 to 100 fold lower than in the lysed cell preparation. PMID- 1509406 TI - Defibrotide inhibits platelet activation by cathepsin G released from stimulated polymorphonuclear leukocytes. AB - Defibrotide is a polydeoxyribonucleotide with antithrombotic effects in experimental animal models. Most of the actions of this drug have been observed in in vivo test models but no effects have been reported in in vitro systems. In this paper we demonstrate that defibrotide interferes with polymorphonuclear leukocyte-induced human platelet activation in vitro. This effect was not related to any direct interaction with polymorphonuclear leukocytes or platelets, but was due to the inhibition of cathepsin G, the main biochemical mediator of this cell cell cooperation. Since cathepsin G not only induces platelet activation but also affects some endothelial cell functions, the anticathepsin G activity of defibrotide could help to explain the antithrombotic effect of this drug. PMID- 1509407 TI - A soluble recombinant factor VIII fragment containing the A2 domain binds to some human anti-factor VIII antibodies that are not detected by immunoblotting. AB - Human factor VIII (fVIII) inhibitors are pathologic antibodies that inactivate fVIII. A cDNA clone was modified to encode fVIII amino acid residues 373-740 for expression in a baculovirus vector in insect cells. The encoded protein fragment H2 was produced as a soluble, secreted protein, and it was used to test inhibitor plasmas for the presence of antibodies that were not detected by immunoblotting. Seven of 13 inhibitors that bound only to the fVIII light chain by immunoblotting also bound to fragment H2 in an immunoprecipitation assay. Thus multi-chain inhibitor reactivity of inhibitors is more frequent than previously reported. One of these inhibitors was shown to share the epitope for other inhibitors that bind to H2 within amino acid residues 373-541 in immunoblotting assays. The sensitive immunoprecipitation assay described allows determination of relative H2 binding capacity of the total IgG and epitope localization of inhibitors that cannot be similarly characterized by immunoblotting. PMID- 1509408 TI - Comparison between a one-point dilute phospholipid APTT and the dilute Russell viper venom time for verification of lupus anticoagulants. AB - In the present study, the dilute Russell viper venom time (RVVT) and the dilute phospholipid activated partial thromboplastin time (PL-APTT), which are two assays used for the verification of lupus anticoagulants (LA), were modified to increase standardization. The modified assays were then compared with respect to sensitivity and specificity in detecting LA in plasmas from 72 patients with a prolonged APTT. Modifications included utilizing a single dilution of phospholipid that was either bovine brain thromboplastin (Thrombofax) or liposomes comprised of phosphatidylcholine/phosphatidylserine, and expressing the results as a ratio of the clotting times of the mixture of patient and normal plasma/clotting time of normal plasma. In the RVVT, the correlation coefficient between assay results for liposomes and Thrombofax was 0.88 and in the PL-APTT, the correlation was 0.68. A positive test for LA was defined as a ratio of greater than or equal to 1.3 for the PL-APTT with liposomes and greater than or equal to 1.2 for the PL-APTT with Thrombofax and the RVVT with Thrombofax or liposomes. Regardless of the phospholipid source in the test system, the PL-APTT demonstrated higher sensitivity and the RVVT showed greater specificity in detecting patient plasmas that contained antiphospholipid antibodies. PMID- 1509409 TI - The role of phospholipids and the factor VII Gla-domain in the interaction of factor VII with tissue factor. AB - Whether or not the factor VII Gla-domain is involved in the high-affinity interaction of factor VII and tissue factor via calcium-dependent interactions with surrounding phospholipids is unknown. To investigate this, we have purified the factor VII Gla-peptide (FVII-GP) from digested recombinant human factor VIIa and assessed its effect on factor VII:tissue factor interactions. FVII-GP inhibited the activation of factor X by factor VIIa in the presence of either soluble or cell surface tissue factor half-maximally at 0.5 microM and 2.7 microM, respectively. However, FVII-GP failed to inhibit the specific binding of factor VIIa to cell-surface tissue factor, and did not inhibit the ability of tissue factor to stimulate the amidolytic activity of factor VIIa. Unrelipidated tissue factor apoprotein stimulated the amidolytic activity of factor VIIa to the same extent as relipidated tissue factor apoprotein. These findings suggest that the factor VII Gla-domain does not directly interact with tissue factor, but rather is important for calcium binding and concomitant expression of other factor VII epitopes necessary for tissue factor recognition and binding. To test this hypothesis, we have prepared a monoclonal antibody against a putative factor VII epitope that participates in the interaction of factor VII with cell-surface tissue factor (peptide 195-206) and assessed its ability to bind to factor VII in the presence and absence of calcium. Binding of this monoclonal antibody (PW-4) to intact factor VIIa was calcium-dependent and could be inhibited in a dose dependent manner by peptide 195-206.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1509410 TI - G4120, an Arg-Gly-Asp containing pentapeptide, enhances arterial eversion graft recanalization with recombinant tissue-type plasminogen activator in dogs. AB - The effects of G4120, a cyclic Arg-Gly-Asp (RGD) containing peptide which inhibits fibrinogen binding to the platelet receptor GPIIb/IIIa, on thrombolysis with recombinant tissue-type plasminogen activator (rt-PA) were investigated in a combined arterial and venous thrombosis model in heparinized dogs. The arterial thrombus model consisted of a 3 cm everted (inside-out) carotid arterial segment inserted into a transsected femoral artery which occludes within 30 min with platelet-rich material and which is resistant to recanalization with 0.5 mg/kg rt PA. The venous thrombus was a 125I-fibrin labeled whole blood clot produced in the contralateral femoral vein. In 5 dogs given an intravenous bolus of 0.05 mg/kg G4120 followed by a continuous infusion of 0.05 mg/kg per hour for 3 h (group I), arterial occlusion persisted throughout a 4 h observation period and was still present at 24 h in all dogs; the extent of venous clot lysis after 120 min was 27 +/- 7%. In 5 dogs given the same infusion of G4120 in combination with 0.5 mg/kg rt-PA over 60 min, recanalization of the arterial graft occurred in all dogs, within 13 +/- 2 min and persisted throughout the observation period of 4 h (p = 0.01 versus G4120 or rt-PA alone); at 24 h, however, all grafts were occluded. Venous clot lysis in this group was 75 +/- 8% (p = 0.002 versus G4120 alone and p = NS versus rt-PA alone). Pathologic analysis revealed platelet-rich or mixed thrombus with platelet-rich and erythrocyte-rich zones.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1509411 TI - Comparison of recombinant plasminogen activator inhibitor-1 and epsilon amino caproic acid in a hemorrhagic rabbit model. AB - A rabbit ear model of blood loss was developed to compare the effects of an active form of recombinant plasminogen activator inhibitor-1 (rPAI-1) with epsilon amino caproic acid (EACA) in antagonizing tissue-type plasminogen activator (r-tPA)-induced blood loss. The antagonism of both rebleeding, which occurs as a result of hemostatic plug degradation, and r-tPA-induced hemorrhage, where rabbits lose approximately 30% of their blood volume, was studied. rPAI-1 (1 mg/kg i.v.) or EACA (70 mg/kg i.v.) antagonized the rebleeding induced by r tPA (10 micrograms kg-1 min-1) to a similar extent. In the hemorrhagic studies, rPAI-1 effectively antagonized the r-tPA-induced hemorrhage with an ED50 of 3 mg/kg i.v., while the ED50 obtained for EACA was 230 mg/kg i.v. rPAI-1 may be of value in reversing r-tPA-induced blood loss during thrombolytic therapy or in clinical situations where excessive fibrinolysis contributes to bleeding. PMID- 1509412 TI - On the fibrinolytic system in aged rats, and its reactivity to endotoxin and cytokines. AB - Aged rats are more susceptible to endotoxin-induced effects, including microthrombosis and platelet aggregation, than are young rats. To investigate whether changes in the fibrinolytic system might be involved, we investigated the fibrinolytic activity in plasma euglobulin fractions and tissues (lung and heart) of young (6-months old) and aged (24-months old) rats under baseline conditions and after challenge with endotoxin. Aged rats had lower plasma levels of tissue type plasminogen activator (t-PA) and of urokinase-type PA (u-PA) activity. PA inhibitor (PAI) activity was higher in the plasma of aged rats, as was t-PA activity in lung and heart. Rats were treated with either a low dose (1 microgram/kg) or a high dose (10 mg/kg) of endotoxin. Both treatments induced a transient phase of increased blood fibrinolytic activity, as evidenced by higher levels of tissue-type plasminogen activator (t-PA) activity and decreased levels of PA inhibitor (PAI) activity. Over time, the fibrinolytic activity decreased, probably due to increased levels of PA inhibitor. Both the early increase in t-PA activity, and the subsequent increase in PAI activity, were more pronounced in the aged rats, as compared with the younger rats, after the high dose of endotoxin. The aged rats also responded to an injection of interleukin-1 beta or tumor necrosis factor-alpha with a larger increase of PAI activity than did the younger rats. Together the data suggest that, compared to young rats, aged rats have a decreased base-line plasma fibrinolytic activity, while their fibrinolytic system is more responsive to challenge by endotoxin and cytokines. PMID- 1509413 TI - Characterization of three alboaggregins purified from Trimeresurus albolabris venom. AB - Alboaggregins (AL-A, AL-B, AL-C) isolated from Trimeresurus albolabris snake venom represent a new family of proteins which bind to platelet glycoprotein Ib (GPIb). These alboaggregins were purified to homogeneity with ion exchange HPLC (Mono-Q column) and hydrophobic HPLC (TSK Phenyl-5PW column). On SDS polyacrylamide gel electrophoresis, apparent molecular weights of AL-A, AL-B and AL-C were 52 kDa, 26 kDa, and 121 kDa respectively, under nonreducing conditions. Upon reduction, each alboaggregin showed two types of chains with apparent molecular weights in the range of 15-20 kDa. All three alboaggregins agglutinated formalin-fixed platelets. Agglutination activities and binding of labeled alboaggregins to GPIb were specifically inhibited by the monoclonal antibody AK2 which is directed against the 45 kDa N-terminal region on GPIb, but not by monoclonal antibodies against other epitopes on GPIb. 125I-alboaggregin binding to platelets was not altered by the presence of thrombin. Alboaggregins did not bind to GPIIb/IIIa. Alboaggregins were competitive inhibitors for 125I-bovine vWF binding to platelets. Mutual competition studies between AL-A, AL-B and AL-C for the binding of labeled bovine vWF and AL-B to platelets demonstrated that AL-B and AL-C had a significantly higher affinity than AL-A. PMID- 1509414 TI - Prolonged bleeding time of Chediak-Higashi cats corrected by platelet transfusion. AB - Cats with the Chediak-Higashi syndrome (CHS) have a platelet storage pool deficiency (SPD). Ten CHS cats were transfused with a concentrate of 51Cr-labeled platelets prepared from normal donor cats. One hour after transfusion, the donor platelet count in CHS recipient cats was 40,000-60,000/microliters. Bleeding time before transfusion was 9.1 +/- 3.0 min. When donor platelet count in CHS cats was 50,000/microliters, bleeding time was 1.7 +/- 0.2 min. Bleeding time of normal cats was 1.4 +/- 0.3 min. Bleeding time increased to 3.3 +/- 0.2 min and to 5.3 +/- 0.2 min when the platelet count was 30,000/microliters, and 15,000/microliters, respectively. The close inverse relationship between bleeding time and number of donor platelets in CHS cats (r = -0.92), suggests that prolonged bleeding time is due to a platelet abnormality, that platelet transfusion can effectively correct prolonged bleeding time in an animal model of platelet SPD and that CHS cats may be an appropriate animal model to evaluate hemostatic capabilities of transfused platelets. PMID- 1509415 TI - Effects of heparin and endothelial cell growth supplement on haemostatic functions of vascular endothelium. AB - Heparin in combination with endothelial cell growth factor (ECGF) affects physiological responses and growth of human umbilical vein endothelial cells (HUVEC). We have examined the effect of heparin, crude ECGF (endothelial cell growth supplement [ECGS]), or both on the basal and thrombin challenged output of metabolites by HUVEC. The supernatant and/or cell lysate was assayed for released prostacyclin, von Willebrand factor, tissue plasminogen activator, plasminogen activator inhibitor and thrombospondin. Heparin modified release of all these metabolites when in combination with ECGS, and in general these responses were the opposite of those generated by inflammatory mediators such as interleukin-1. It has been postulated that heparin acts by potentiating the effect of ECGF, but heparin inhibited thrombospondin release and enhanced that of von Willebrand factor in the absence of ECGS, while ECGS alone inhibited release of plasminogen activator inhibitor. Thus, under our experimental conditions it would appear that heparin and crude ECGF can affect HUVEC independently of one another. PMID- 1509416 TI - Anticardiolipin antibodies in acute venous thromboembolism. PMID- 1509417 TI - Artificial prolongation of the prothrombin time of lyophilized plasma induced by transportation with solid carbon dioxide. PMID- 1509418 TI - Deterioration of reference material for human thromboplastin. PMID- 1509419 TI - Risk of HCV infection in haemophiliacs treated with a dry-heated factor VIII concentrate. PMID- 1509420 TI - Is a hypercoagulable state present in hypothyroidism? PMID- 1509421 TI - Follow-up: a young man with three deficiencies of antithrombotic proteins, asymptomatic until now, spontaneously develops pulmonary embolism. PMID- 1509422 TI - [Medical genetics at a cross-road]. PMID- 1509423 TI - [Resuscitation in a health institution]. PMID- 1509424 TI - [Decision to withdraw cardiopulmonary resuscitation at Norwegian hospitals]. AB - We present a survey on the use of do-not-resuscitate orders in Norwegian hospitals based on mailed questionnaires. 559 doctors, at least one from every somatic hospital in Norway responded. Do-not-resuscitate orders were issued by 92% of these doctors. There were large differences, however, as to who made the decision, who was involved in the decision-making, the consequences of a do-not resuscitate order, and how the orders were documented. Formal rules for do-not resuscitate orders are needed. PMID- 1509425 TI - [Use of the R-concept in a medical department]. AB - Do-not-resuscitate orders issued in a medical department were studied by retrospective evaluation of 195 consecutive deaths in the department in 1991. No attempt at resuscitation was recorded in 171 patients. In these cases, do-not resuscitate orders were documented in 67 only. For more than half of the orders, no reason was given in the medical record, and partial orders not to resuscitate were found in five patients only, none of whom were resuscitated. No difference was found in use of do-not-resuscitate orders between intensive-care units and regular wards, between patients above and patients below 80 years of age, or between patients with and patients without cancer. We suggest extended use of do not-resuscitate orders in our department, and better documentation of the orders. Written guidelines have been established for this purpose. PMID- 1509426 TI - [Computer tomography after reconstructive vascular surgery of the abdominal aorta. Can fluid around the aortic prosthesis be considered a normal finding?]. AB - 15 patients who had elective aortic reconstruction for infra-renal aortic aneurysm (nine patients) or aortoiliac occlusive disease (six patients) were evaluated using postoperative computerized tomography. The assessment was performed 1-2 weeks, 6-8 weeks and 6-8 months after implantation of woven Dacron graft. All patients were without clinical or laboratory signs of infection. The presence or absence of retroperitoneal air or fluid collections was assessed. In patients operated on for aneurysms, perigraft fluid was present in two cases 6-8 weeks after operation, but had disappeared within 6-8 months. Even after only 1-2 weeks, no accumulation of periprosthetic fluid was found in patients operated on for occlusive disease. Retroperitoneal air was not seen in any of the cases. It is concluded that perigraft fluid may be a "normal" phenomenon during the early postoperative period in patients operated on for abdominal aortic aneurysm. PMID- 1509427 TI - [New therapeutic possibilities with drugs affecting serotonin receptors]. AB - The past decade has seen important progress in understanding the localization, pharmacology, and function of serotonin (5-HT) receptor subtypes. At least seven subclasses have been shown to exist, and evidence is emerging to suggest further subclassification. Serotonin is involved in numerous physiological processes (e.g. feeding, sleep, pain, sexual behavior, temperature regulation) and pathophysiological ones. Serotonin reuptake blockers have been found effective in the alleviation of depression and attacks of panic, and are at varying stages of clinical evaluation in the treatment of obsessive compulsive disorder, chronic pain, and bulimia nervosa. Selective potent serotonin receptor agonists and antagonists show promise in the treatment of migraine, nausea and vomiting, schizophrenia, anxiety, hypertension, and Raynaud's disease. PMID- 1509428 TI - [Mucosal lesions associated with antiphlogistics--treatment and prevention]. AB - Gastrointestinal side effects associated with nonsteroidal, anti-inflammatory drugs are well known, but recent data suggest that the small and large bowel are target organs in addition to the gastroduodenal mucosa, although the clinical significance of changes in permeability and of mucosal inflammation is unknown. Inhibition of prostaglandin synthesis remains the major pathogenetic hypothesis for the entire gastrointestinal tract, but additional mechanisms are probably involved. Ulcers that occur during non-steroidal anti-inflammatory drug therapy can be treated in the same way as other peptic ulcers, but the duration of treatment should be extended if the non-steroidal anti-inflammatory drug cannot be withdrawn. Prophylactic therapy with H2-antagonists or prostaglandin analogues may be justified in selected high risk individuals. PMID- 1509429 TI - [Treatment of acute hypergranular promyelocytic leukemia with all-trans-retinoic acid]. AB - Two patients with relapsed hyper-granular promyelocytic leukemia were treated with all-trans-retinoic acid. Both obtained complete remission with minimal transfusion requirements, no haemorrhagic complications or serious infections, and involving short periods of hospitalization. This course of events corresponds well with previously published information from larger patient materials, which are also discussed in the article. PMID- 1509430 TI - [Attitude of blood donors towards cholesterol measurement]. AB - In analyses of cost-effectiveness it is customary to count knowledge of having a high serum cholesterol level as a negative factor. There is little support for this practice in the literature. We have studied the attitude of 305 Norwegian blood donors towards cholesterol testing. 63% stated that they were interested in their serum cholesterol level, and 40% said they knew their own serum cholesterol level. The attitude towards cholesterol testing was clearly positive, both among men and among women, regardless of age. Only one donor stated that she did not want to have her serum cholesterol tested in conjunction with blood donation. PMID- 1509431 TI - [Treatment of relatives]. AB - The article addresses the physician's relationship to the next of kin of multi traumatized patients. The various phases of grief are discussed:phase of shock, lack of emotion, disturbance of the imagination, sense of guilt, as well as aspects connected to donation of organs. Finally three case reports are presented to further illustrate the points made in the article. PMID- 1509432 TI - [Neurobiological aspects of addictive drugs]. AB - Increasing insight into the molecular and cellular mechanisms of drugs of abuse has been obtained during the last decade. Such drugs exert several of the effects related to their abuse potential by interacting with the mesocorticolimbic dopaminergic system. Single doses of several drugs of abuse increase dopamine activity in nucleus accumbens, which is related to reward and reinforcement. Repeated administration may result in development of tolerance, but also in behavioral sensitization and conditioning. These processes alter subsequent drug related behaviours and may contribute to relapse to drug taking. PMID- 1509433 TI - [Contact tracing in genital chlamydia infections]. AB - Only one in five general practitioners in Norway initiates notification of partner(s) after diagnosing a case of genital chlamydial infection. In order to increase the use of this efficient case-finding method we review the aims of notifying partners and the judicial, ethical and economical aspects of the method. We describe both provider-referral and patient-referral methods. The first approach is chosen when the index patient wants to remain anonymous. General practitioners are advised not to give the index patient medication for the contacts. Instead, the contacts should be examined and informed by qualified personnel. Notification of partner will be a cornerstone in the struggle to control the current epidemic of genital chlamydial infection in Norway. PMID- 1509434 TI - [Infection problems in the leukopenia phase after autologous bone marrow transplantation]. AB - Between 1986 and 1991, 29 patients with malignant lymphomas were treated with total body irradiation and high-dose chemotherapy followed by autologous bone marrow transplantation at the Norwegian Radium Hospital. Owing to treatment induced bone marrow toxicity, the leucocyte count in peripheral blood rapidly fell to zero. The aplastic phase lasted for 25 days (median). All patients experienced fever in the posttransplant period and needed broad-spectrum antibiotics. 12 patients had documented bacteremia, mostly with Gram-positive isolates. There were seven cases of documented focal infections, and antibiotic associated colitis was seen in two cases. Other complications included bleedings and skin rashes. Four patients died in the post-transplant period from complications related to the cytotoxic treatment. We discuss guidelines for antimicrobial treatment of suspected and confirmed infections in neutropenic patients. PMID- 1509435 TI - [Use of the venous port]. PMID- 1509436 TI - [Contact tracing routines for genital chlamydia infections used by Norwegian physicians. A questionnaire study]. AB - Notification of partner(s) is recommended as a measure to control the epidemic of genital chlamydial infection. We surveyed a random sample of Norwegian general practitioners and privately practising gynaecologists. Only one in five general practitioners initiated notification of partner(s) after diagnosing a patient with genital chlamydial infection. A proposed new Communicable Diseases Act will make it mandatory to notify the partner in the event of such infections. 49% of general practitioners are in favour of the proposal, 21% oppose it while 30% remain uncertain. After implementation of similar legislation, Sweden has experienced a decline in the incidence of genital chlamydial infection. We believe increased notification of partner would help to control the Norwegian epidemic. PMID- 1509438 TI - [Environmental medicine--status and challenges]. PMID- 1509437 TI - [The calendar as criterion--duration of sick leave and physicians' work conditions]. AB - This paper addresses physicians' tendency to allot standardized, "rounded off" sick leave. Of the 401 sick leaves reviewed, 64.3% lasted for one or two weeks, one or two months, or to the end of the week or month. The patients' presumed wish for an extended leave, and the practitioners' strained work situation were examined as possible influential factors. A scrutiny of general practitioners' and company practitioners' working conditions, and employees' current inclination to work, does not support these ideas. Dialogue between physician and patient should be improved and we also suggest a change to "vaguer" durations of sick leave. PMID- 1509439 TI - [Sore throat--sore science]. PMID- 1509440 TI - [Physician--in the service of technology or humanity?]. PMID- 1509441 TI - [A valuable search program for Medline]. PMID- 1509442 TI - [Immigration and AIDS]. PMID- 1509443 TI - [Admission criteria for medical studies]. PMID- 1509444 TI - [The quackery low prohibits physical therapists from calling themselves specialists]. PMID- 1509445 TI - [Meeting between physicians and companies]. PMID- 1509446 TI - [Alternative medicine--a medico-ethical dilemma?]. PMID- 1509447 TI - [Anaphylactic reactions during general anesthesia]. PMID- 1509448 TI - [Arrhythmias caused by anti-arrhythmia agents]. PMID- 1509449 TI - [Breast reduction]. PMID- 1509450 TI - [Treatment of systemic fungus infections]. PMID- 1509451 TI - [Systemic mycoses. Epidemiology, clinical aspects, diagnosis]. AB - Systemic mycoses are serious, often life-threatening, infections that are encountered with increasing frequency in many countries. These infections are most often seen as a result of advanced medical treatment leading to profoundly immuno-suppressed patients. In Norway, most systemic mycoses are caused by Candida, followed by Aspergillus, Cryptococci and Mucorales. This paper deals with the pathogenetic and immunologic mechanisms underlying these infections. The different agents are described, and the various clinical manifestations. A discussion of the diagnosis of systemic mycoses is followed by some general considerations regarding treatment. PMID- 1509453 TI - [Ferritin concentration in serum in health adults. Significance for blood donation]. AB - Serum ferritin levels were measured in 613 women and 376 men included in our Blood Donor Registry in 1990, prior to their first donation. The mean serum ferritin was 34 micrograms/l in females and 98 micrograms/l in males. For men less than 20 years of age mean serum ferritin was 52 micrograms/l which is significantly lower than for the other age groups. For women greater than or equal to 50 years of age mean serum ferritin was 61 micrograms/l, which is significantly higher than for the younger age groups. In 22% of the women and 1.3% of the men serum ferritin was less than 15 micrograms/l upon registration. Female blood donors with an initial serum ferritin of less than 10 micrograms/l had donated on average 1.2 times 11 to 23 months later, and 56% were temporarily or permanently deferred from donation. Females with an initial serum ferritin of between 30 and 39 micrograms/l had donated 2.5 times, and 26% were deferred. PMID- 1509452 TI - [Reduction mammaplasty in breast hypertrophy]. AB - Between January 1984 and November 1990 a total of 292 patients underwent reduction mammaplasty for hypertrophic breasts. Of these patients, 233 had a superomedial pedicle (Orlando's method) and 36 an inferior pedicle (Robbins' method). 23 had various other operations. The patients operated on by Orlando's and Robbins' method were compared retrospectively. It was found that Robbins' method was superior in younger women, owing to increased sensitivity of the nipple-areola complex, and lactation. In the physicians' opinion, wide scars developed in 32% of the patients. In our opinion closing the wound with intracutaneous suture might improve the quality of the scar. Of the patients assessed, 98% were satisfied with the physical outcome of the operation and 86% with the cosmetic outcome. The operative technique of the two methods is described. PMID- 1509454 TI - [Catecholamine release--unpredictable side effects of calcium antagonists]. AB - Animal and in vitro studies have shown that calcium antagonists release noradrenaline from sympathetic nerves. Several calcium antagonists interact with the catecholamine storage vesicles in a way that reduces the ability of the vesicles to take up and store catecholamines. Clinical studies indicate that verapamil and nifedipine increase release of noradrenaline from the heart during ischemia. Calcium antagonists thus have a direct catecholamine-releasing effect that may be clinically relevant (may induce negative side effects). PMID- 1509455 TI - [Congenital myotonic dystrophy]. AB - Congenital myotonic dystrophy is a distinct entity causing severe hypotonia and other neuromuscular manifestations. The disease is usually inherited from the mother and shows a more severe course than the adult form of dystrophia myotonica. Congenital myotonic dystrophy is associated with increased perinatal mortality. We describe a case with this disorder and discuss the differential diagnosis in relation to other neuromuscular disorders causing hypotonia in early life. PMID- 1509457 TI - [Poisoning with long-acting anticoagulants]. AB - Until last year, all rodenticides that could be marketed freely in Norway contained anticoagulants. In recent years rodenticide manufacturers have replaced warfarin by so-called "superwarfarins" as the active substances in their products. The latter are more toxic, also in a human context. One single intake can produce an anticoagulatory effect which may last for 50 to 60 days, and the intake of larger quantities over a period of time can induce the same effect for close to seven months. We describe two patients who were poisoned with bromadiolone. One of them had to be treated with vitamin K1 for six months. Reference is further made to similar casuistics described in the literature. Finally, the authors outline a recommended method of treatment. PMID- 1509458 TI - [Fluconazole--a new antifungal agent]. AB - Fluconazole (Diflucan) is a new triazole antifungal agent that is effective against a wide range of fungi and has a favourable pharmacokinetic profile. Fluconazole is absorbed well after oral intake independent of food intake. Fluconazole is given once daily, in a dose of 50-400 mg. The dosage is the same for oral and parenteral administration. Tissue penetration is good, as is the concentration in cerebrospinal fluid. Fluconazole should not be given to children under 16 years of age, nor to pregnant or breast-feeding women. In Norway, fluconazole is indicated for treatment of candida vaginitis that is resistant to other treatment, invasive candida infection, candida stomatitis in immunocompromised hosts, and cryptococcal meningitis. PMID- 1509456 TI - [Intestinal lymphoma presented as multiple intestinal polyposis]. AB - Primary gastrointestinal lymphoma is a rare condition. It constitutes approximately 5% of all lymphoid malignancies. Primary lymphomas of the intestinal tract rarely present as multiple polyposis. We describe such a patient who was treated with chemotherapy. The treatment of choice is surgery when possible. Chemotherapy is used in addition when high grade non-Hodgkin lymphoma is revealed. Chemotherapy should be used for patients who are unable to undergo curative resections. Prognosis is poor for patients with a non-resectable disease. PMID- 1509459 TI - [Treatment of gynecologic bleeding disorders]. AB - Conclusions reached at an expert meeting arranged by the Medical Products Agency (Lakemedelsverket) in Sweden on the treatment of gynaecological bleeding disorders are presented. An active approach to endometrial diagnosis is recommended when bleeding is protracted and does not respond to medication, and when bleeding occurs more than one year after menopause. A period of expectation is permissible in women younger than 45 years. Exfoliative endometrial diagnosis is highly sensitive and specific and, in recent years, the traditional curettage has been reappraised as the first method of choice. Bleeding during anovulatory cycles is usually managed by treatment with progestagens. Menorrhagia may be diminished by oral contraception, tranexamic acid or NSAID. Endometrial resection offers a promising alternative to hysterectomy. Genital infection is another common cause of irregular bleeding in sexually active women and must be treated before invasive procedures are undertaken. Abnormal bleeding in patients with endometriosis often improves as a result of the treatment given to alleviate other symptoms such as pain. Bleeding irregularities caused by gynaecological malignancy, particularly contact bleeding in cancer of the cervix, are seen during the reproductive years and are accessible for diagnosis. The authors also discuss irregular bleeding caused by coagulopathia or treatment with hormones, as well as the effect of antifibrinolytic drugs. PMID- 1509460 TI - [Evaluation of virological/serological parameters for hepatitis B]. PMID- 1509461 TI - [Expert witness in cases of rape]. AB - The decision to try a rape case in court may depend on the medico-legal evidence documented by a doctor. Generally, doctors have little knowledge of expectations and requirements in court regarding testimony and expert opinion. In 1990, the Norwegian Directorate of Health recommended that victims of rape and violence all over the country--independent of police notification--be offered a medical and a medico-legal examination and follow-up. The Oslo Emergency Hospital has practised this health service for six years. The article describes the Oslo routine as a basis for doctors with little or no knowledge of the subject. Rape trauma, a variant of post-traumatic stress disturbance, manifests over time as physical, psychological and social reactions which influence the patient's health. The doctor must therefore follow the patient over time in order to apply this diagnosis. Rape trauma may be unknown to the court; a reason why the doctor should inform the prosecutor if it is decided that the case is to be tried in court. In order to document rape trauma as evidence the doctor must be called as an expert medical witness and not as an ordinary witness. PMID- 1509462 TI - [Are silicone breast prostheses dangerous?]. AB - Since 1964 silicone breast prostheses have been implanted in 5 million women for breast reconstruction after cancer operations, to correct congenital deformities and for cosmetic reasons. There is no evidence in the literature of a correlation between silicone implants and breast cancer. Some authors claim that silicone implants reduce the reliability of mammography. Autoimmune diseases in patients with silicone mammary implants are reported in less than 40 cases. Most of these are localized or systemic scleroderma. An association with silicone implants has been suggested, but this suggestion has not been confirmed by scientific data. PMID- 1509463 TI - [A cerebrovascular unit. Experiences after 8-years of activity]. AB - The authors review experience gained from developing and running a non-intensive stroke unit during the years 1983-91. The number of patients treated per year has increased from 65 to 149. The average length of stay in hospital has dropped from 21 to 15 days. About 87% of the patients had verified stroke, 7% had transient ischemic attacks (TIAs). Other intracranial diseases were found in 3.3%. The mortality rate was low (5%) 48% of the patients were transferred to a rehabilitation centre, 37% were discharged to their homes, with or without out patient care, and 10% were discharged to nursing homes. Early and systematic investigations and multi-disciplinary rehabilitation in a specialized stroke unit increases the quality of care for patients suffering from stroke. A shorter stay in hospital gives a bonus in the form of reduced health expenditures. PMID- 1509464 TI - [Gingival hyperplasia induced by calcium channel blockers. Rare or frequent in Norway?]. AB - Sales statistics indicate that the number of Norwegians treated with calcium channel blockers increased from about 50,000 in 1986 to about 83,000 in 1991 (last year: nifedipine 39%, verapamil 27%, amlodipine 21%, diltiazem 10% and felodipine 3%). In spite of widespread use, only one report on gingival hyperplasia induced by calcium channel blockers has been received by the Norwegian Adverse drug reaction committee. The incidence of this adverse reaction is uncertain, but the few controlled studies that have been performed indicate that it may be as high as 15% in patients on long-term treatment, at least with nifedipine. This corresponds to nearly 5,000 cases among the about 32,000 users of nifedipine. Norwegian physicians and dentists are asked to report cases of gingival hyperplasia induced by calcium channel blockers. Although the voluntary report system is fraught with uncertainty, it is hoped that, in a relatively small and surveyable drug market as the Norwegian, the reporting may provide some relevant information, e.g. to allow comparison of the potential of the various calcium channel blockers to induce this adverse effect. A Norwegian controlled study on gingival conditions among long-term users of calcium channel blockers is in its initial stage. It may be of interest to compare the results of this study with the indications obtained from the spontaneous reporting on the incidence of this adverse effect, which is relatively easy to diagnose. PMID- 1509465 TI - [Intravenous drug users and the HIV epidemic]. AB - Data are taken from a study of 1,765 arrested intravenous drug users at the Oslo Central Police Station. Intravenous drug users in Oslo seem to get themselves tested for HIV regularly. In 1990-91 the average number of HIV-tests was 5.3, and the time since last test was, an average, between eight and nine months. Most intravenous drug users do not share needles and syringes. The most important source of needles and syringes in Oslo is an ambulant bus which can be found in city centre at night. HIV-seropositive drug users seem to have more regular contact with treatment programmes than those who are HIV-seronegative. Most of the HIV-seropositive drug users who are under treatment are to be found in a few institutions. PMID- 1509466 TI - [What symptoms and complaints result in sick-listing? ICPC-coding of patients' own opinion in general practice]. AB - The aim of this study was to describe which complaints patients themselves regard as the cause of sickness certification. During one week in April 1986, 1,379 patients in Buskerud county, Norway, filled in a form after receiving an initial certificate of illness or a continuation certificate from a general practitioner. International Classification of Primary Care (ICPC) no. 1-29 was used to classify the patients' symptoms and complaints. More than half of the patients (53%) considered pain in the musculoskeletal system, particularly back pain (22%), as the reason for their sickness certification. Physical work load was assumed to be a contributory cause to the complaints by 66% of the patients certified sick because of back pain, 58% of those certified sick due to cervical spine and shoulder symptoms, and 72% of those with myalgia, fibrositis (ICPC no. L18, L19). 29% of the patients meant that their health problems could have been prevented, and 15% reported that they could have continued work if their jobs had been adjusted because of their condition. PMID- 1509467 TI - [Doxycycline preparations]. PMID- 1509468 TI - [Criteria for qualification for medical education]. PMID- 1509469 TI - ["The doctor said"]. PMID- 1509470 TI - [Scullcap--liver damage]. PMID- 1509471 TI - [The question of compensation for animal epidemics--general legal principles and discussion of selected verdicts]. AB - A summary is given of general and specific aspects and jurisdiction in connection with sections 66-71 (compensation for damages of the German animal epidemic law). The author can be contacted for specific details. PMID- 1509472 TI - [An elephant tusk with a spear injury]. AB - This tusk specimen contains a metal spear with a wooden component, which is surrounded by a quiver-like osseous encasement. The injury was probably caused by a drop-spear trap. The spear entered the tusk through the base of the pulp. The osseous encasement is constructed by pulpocytes which turned to odontoblasts after stimulation and are responsible for the development of secondary dentine. Secondary dentine is characterized by its irregular arrangement of dentine tubules, in contrast to those of true ivory. PMID- 1509473 TI - [Cellulose acetate electrophoresis, radial immunodiffusion and nephelometry- comparative methods for the determination of albumin]. AB - Different methods for the determination of albumin in dogs and cats are compared. Nephelometry was found to be the method of choice, due to its excellent precision, the immediate test results and the wide measuring range. The advantage of the radial immunodiffusion method is that expensive equipment need not be acquired, which makes the test profitable for small amounts of samples. At the expense of accuracy, electrophoresis enables the simultaneous evaluation of all protein fractions. PMID- 1509474 TI - [The clinical case. Poisoning in a swine breeding and fattening facility]. PMID- 1509475 TI - [The effect of environmental factors on the occurrence of udder diseases]. AB - The influence of housing factors on udder diseases was investigated in 2156 tiestall barns with 41893 cows and in 98 loose housed herds with 4126 cows. In loose housed herds less teat injuries were observed and also less mastitis than in tiestall barns. Within the different tiestall systems there was a trend to more udder diseases in short standings with a dung grid than in other systems. The ordinary neck chain and the "Grabner"-tethering system showed better results than the horizontal chain and the yoke tying system. Stall partitions between the cows caused a marked reduction of udder diseases. The installation of a cow trainer showed advantages regarding udder diseases. Inaccurate standing measurements (length and width) caused more udder diseases. When the metal grid was in poor condition, the incidence of teat injuries as well as udder diseases of heifers increased. Teat injuries and udder infections were more frequent when limb or digit injuries were found. Regular hoof care twice a year reduced the udder disease rate. Bedding material influenced the incidence of udder diseases positively. On farms where the cows were on pasture, the incidence of udder infections was higher than on farms where the cows were permanently housed. Heifers that were tied as calves or as juveniles showed significantly less udder diseases than those that were raised in groups. Faults in milking, defects in milking machines and deficits in milking hygiene showed a negative effect on udder diseases. PMID- 1509476 TI - [Infection with Leptospira interrogans, serovar mozdok, in cattle]. AB - In East Germany the same serovar, Leptospira mozdok, of the Pomona serogroup is found in cattle as well as in swine populations (Zieris 1989). Nowadays cases of bovine leptospirosis caused by infection with L. pomona have no significance. There are marked epizoological differences between infection with L. mozdok and L. pomona. The main source of infection with L. mozdok for cattle is the black striped field mouse (Apodemus agrarius). Secondary homonomous transmission occurs among the cattle. The clinical course of both infections is the same--including peracute, acute and chronic forms. Important prophylactic measures are effective rodent control and optimising hygiene conditions both in housing and on pasture. Veterinarians in abattoirs must consider leptospirosis in the differential diagnosis in cases with icteric signs, especially when the meat is derived from emergency slaughter. PMID- 1509477 TI - [The clinical effectiveness of FSH-P for induction of superovulation in cattle]. AB - The clinical efficacy of FSH-P for the initiation of superovulation in cattle was examined on 1000 animals of the Deutsche Schwarzbunte and Rotbunte breeds of RPN Verden during the years 1988 and 1989. In untreated cattle only one embryo is found (R. J. Mapletoft 1983, Roselius 1989). In the group of the FSH-P treated animals, the number of transferable embryos was 5.8 +/- 3.6. The 25% percentile was 3 and the 75% percentile was 8. A seasonal dependence was not found. PMID- 1509479 TI - [Selenium poisoning in fattening swine]. AB - A case of selenium toxicosis was observed in fattening pigs. Intoxication was caused by high levels of selenium in a commercial mineral premix. Instead of the recommended dose of 16 ppm Se, the mineral feed contained selenium at concentrations of 657 and 1059 ppm. The ration in use was found to contain more than 14 ppm selenium. Clinical symptoms were observed 5 to 6 weeks after the pigs began consuming the contaminated feed mixture. Feed intake was markedly reduced and animals showed severe lameness due to separation and necrosis of the hoof wall at the coronary band. Some pigs were reluctant to stand. In some cases alopecia was detected. At histopathological examination one animal with paralysis of the hind limbs revealed a focal bilaterally symmetric poliomyelomalacia in the lumbar segment of the spinal cord. Diagnosis was confirmed by high selenium contents of liver, kidneys and blood. After removing the incriminated feed no further pigs developed signs of intoxication. New horn growth was present and lame animals recovered slowly. PMID- 1509480 TI - [The use of tiletamine/zolazepam/romifidine for distant immobilization of wild boars]. AB - The immobilisation of 25 wild boars with a combination of tiletamine/zolazepam/romifidine is described. The applied dose was 3-6 mg/kg BW Tilest 500 and 100 micrograms/kg BW Sedavet. The mean recumbency time was 5-10 min. There were no critical moments during anesthesia, even with pregnant sows. Anesthesia was supervised with a pulse oximeter and a respiration frequency monitor. The oxygen saturation was between 92% and 96%, pulse and respiration rate remained normal. PMID- 1509481 TI - [Restraint methods for bird patients. Theoretical principles and practical implementation. Part 1]. AB - In avian medicine an adequate diagnostic and therapeutic procedure is not possible without restraint. Accidents result most often from the ignorance of certain bird-specific physiological and anatomical characteristics. On the basis of theoretical principles, the different restraint techniques are described and demonstrated by figures in detail. PMID- 1509478 TI - [Rumen fluid studies in calves with abnormal and normal sucking behavior]. AB - Ruminal fluid and blood samples were analysed in 39 calves with poor suckling behaviour and reduced milk intake (group 1) and in 21 calves with normal suckling behaviour (group 2). The pH level and chloride concentration was determined in the ruminal fluid as well as in the blood. In addition Gram stains and subsequent microscopical examinations of the ruminal fluids were carried out. Blood samples were submitted for blood gas analysis. Notable differences were found between the two groups. The pH level of the ruminal fluid was less than 5.5 in 29 of the 39 calves in group 1 (74.4%); in contrast, the pH was always above 5.5 in group 2. In group 1, 22 calves with a pH of less than 5.5 also revealed a metabolic acidosis of the blood. Mainly gram-positive bacteria were found in the ruminal fluid of 74.4% of the calves in group 1. On the other hand, 76.2% of the calves in group 2 revealed a mainly gram-negative flora. There was no difference in the chloride concentration, either in the blood or in the ruminal fluid and the values showed a high range of scatter. PMID- 1509482 TI - [Embryo transfer in cattle]. PMID- 1509483 TI - [Surgical removal of a pedunculated uterine tumor in a donkey mare]. AB - The unusual incidence of a pedunculated fibrosarcoma in the uterus of a donkey is reported. The tumor caused colic-like symptoms and blood tinged vaginal discharge. The diagnosis was made by ultrasound and rectal examination. The patient was successfully treated surgically, by ovariohysterectomy. PMID- 1509484 TI - [Lens-induced uveitis (endophthalmitis phakoanaphylactica) in domestic animals]. AB - In this paper ophthalmological and clinical results as well as the literature on lens-induced uveitis (LIU), a relatively unknown pathological syndrome in domestic animals, are presented. Out of all ocular material sent to the Institute of Pathology, GSF, from 1970 until 1990 (n = 864), 40 individual cases of LIU (14 cases in dogs, 13 in cats, 10 in rabbits, 1 in a horse and 2 in birds) were diagnosed. The histology of the eyes of the cases is characterized by a lesion of the lens capsule and a consequent reactive phacogenic inflammation of the anterior segment of the eye in the region of the anterior uvea. A comparison of the history and ophthalmological diagnosis indicates that 36 lens-induced uveitis cases occurred following a (spontaneous) traumatic injury to the eye, whereby the anterior lens capsule was perforated with the result of the lens material being exuded into the anterior uvea (iris-ciliary body region). The strongly vascularized anterior uvea is used as a carrier and a connecting link to the immune system. None of the histologically examined cases of LIU were diagnosed as such clinically. This can be explained by the fact that the uveitis is difficult to recognize on account of overlying secondary alterations in the eye. Nevertheless the morphological substrate of LIU is considered to be pathognomonic. The inflammatory and cellular reactions leading to a release of the lens material observed in domestic and laboratory animals exhibit only slight parallels to those observed in man. The case history of animals usually reveals a traumatic injury and an endophthalmitis (with or without secondary glaucoma) which cannot be controlled therapeutically. The therapy for promptly diagnosed cases should be a lens extraction to save the affected eye and its sight. In advanced cases the enucleation of the bulbus is the therapy of choice. PMID- 1509485 TI - [Cells in the cerebrospinal fluid of dogs and cats. Part 2]. AB - Three groups of cerebrospinal fluid (CSF) cells can be formed: 1. cells of the normal CSF, such as monocytes, small lymphocytes and occasionally cells of the ventricle system, 2. cells found in dogs and cats with neurologic disorders, such as reactive monocytes and lymphocytes, macrophages, neutrophils and eosinophils in addition to cells of the first group, 3. neoplastic cells. The different cells are introduced and their origin, function and occurrence are discussed. Mitotic figures, degenerated cells and artefacts are also mentioned. PMID- 1509486 TI - [Fresh water aquariums and veterinary practice. 1. Principles of fresh water aquariums]. AB - Although aquarium fish belong to the most frequently-kept pets they are very rare as patients in veterinary clinics. Besides the fact that the cost of the single fish is usually low, one reason might be that a sick fish has always to be seen in the context of its aquarium conditions, and that most veterinarians lack knowledge of required parameters. The following summary is intended to give an overview of the factors that are important for an optimal functioning aquarium, and with that for the health and well-being of the animals. Knowledge of these factors will help in the recognition and prevention of diseases resulting from management faults. PMID- 1509487 TI - Towards a nomenclature system of animal, plant and microbial toxins. PMID- 1509488 TI - Scorpion sting with cranial nerve involvement. PMID- 1509489 TI - Effect of calcium and phosphate ions on hemolysis induced by Pyrularia thionin and Naja naja kaouthia cardiotoxin. AB - Pyrularia thionin is a strongly basic bioactive peptide of 47 amino acids isolated from nuts of Pyrularia pubera. It is hemolytic, cytotoxic and activates an endogenous phospholipase A2 in 3T3 cells. Earlier studies have shown that the cardiotoxin from Naja naja kaouthia has similar activities and binds to the same site as Pyrularia thionin. Since the peptides appear to bind to the phospholipids of cell membranes to elicit their cellular responses, the effect of modifying the electrostatic environment was studied by separately adding phosphate ion and Ca2+, and by removing Ca2+ from the membrane by treatment with EGTA. Analysis of erythrocyte hemolysis for both Pyrularia thionin and cardiotoxin shows that the reactions follow Michaelis-Menten kinetics, with the peptides serving as the substrate. The basal rate of hemolysis in physiological saline is markedly increased by the addition of phosphate in the 5-10 mM range and also by removing membrane-bound Ca2+ by incubation of the cells with 10 mM EGTA. These treatments do not change the apparent K(m) values, but increase the V(max), indicating that more binding sites are made available by these treatments. On the other hand, added Ca2+ in the 5-10 mM range competitively inhibits the reaction by inhibiting the binding of the peptide to the membrane. PMID- 1509490 TI - Binding properties of Pyrularia thionin and Naja naja kaouthia cardiotoxin to human and animal erythrocytes and to murine P388 cells. AB - Pyrularia thionin and snake venom cardiotoxin are strongly basic peptides which induce hemolysis, depolarization of muscle cells and activation of endogenous phospholipase A2. An earlier study of the hemolysis reaction indicated that the two peptides bind to and compete for the same site on human erythrocytes. A recent study examined the hemolysis induced by both peptides as the phosphate and Ca2+ content of the reaction mixture was varied. The results of the recent study (VERNON, L. P. and ROGERS, A., Toxicon 30, 701-709) agree with this companion study on the binding of 125I-labeled pyrularia thionin and cardiotoxin to erythrocytes under the same conditions. Added phosphate ion at 5 mM and removal of membrane-bound Ca2+ by treatment with 10 mM EGTA make more binding sites of the same affinity available to both peptides, which are shown to bind in a competitive fashion to the same site. Addition of 10 mM Ca2+ to the medium decreases peptide binding due to competitive binding of Ca2+ to the same site on the membrane. For human erythrocytes the number of binding sites/cell for the thionin ranged from 0.7 to 1.7 x 10(5) and for cardiotoxin from 0.82 to 1.6 x 10(5). The calculated dissociation constants (Kd) from the Scatchard plots ranged from 0.43 to 1.1 microM for the thionin and from 0.40 to 0.98 microM for the cardiotoxin. The binding sites for thionin and cardiotoxin with sheep erythrocytes were 1.7 and 2.0 x 10(4) sites/cell, respectively, and both cow and horse erythrocytes demonstrated 2.7 x 10(4) sites/cell for the thionin. Binding studies with murine P388 cells showed 7.0 and 9.5 x 10(6) sites per cell for Pyrularia thionin and cardiotoxin, respectively. PMID- 1509491 TI - Mojave toxin affects fusion of myoblasts and viability of myotubes in cell cultures. AB - Mojave toxin is a neurotoxic, heterodimeric phospholipase isolated from the venom of Crotalus scutulatus scutulatus. Responses of primary rat muscle cell cultures and clonal muscle cell lines to treatment with Mojave toxin and its constituent subunits were examined. Continuous exposure of cells to 0.5 microM or 1.0 microM Mojave toxin or the basic subunit, added 24 hr after plating, prevented fusion of primary myoblasts and C2 myoblasts to multinucleate myotubes. Under the same experimental conditions, some myotube formation was observed when RMo cells were used, but the number and size of the myotubes were reduced substantially compared to untreated controls. The addition of Mojave toxin to established myotubes that arose from differentiation of primary myoblasts or C2 myoblasts essentially led to total disappearance of the myotubes from the cell layer within 48 hr. Myotubes from RMo cells treated in the same manner, however, did not disappear, but they were smaller and less numerous than comparable controls. Similar results were generated by exposure of myotubes to the basic subunit of Mojave toxin under the same conditions. The underlying layer of mononucleate cells was retained in both instances. Toxin-free cultures continued to develop in the usual manner. Treatment with 1.0 microM concentrations of the acidic subunit, pancreatic phospholipase A2 or a non-neurotoxic phospholipase from Naja naja atra gave results indistinguishable from untreated control cultures. PMID- 1509492 TI - Morphology of the large granular alveoli of the parotid glands in toad (Bufo ictericus) before and after compression. AB - The parotid glands of toads are constituted by an accumulation of venom-producing granular alveoli. Parotid glands of Bufo ictericus were manually compressed and immediately excised. Normal glands (not submitted to compression) were also excised and processed for histological and ultrastructural observations. The glandular body of large granular alveoli in parotid glands is formed by a myoepithelial layer, internally covered by a syncytial secretory layer. In the normal parotid gland this layer is very electron dense, thus preventing clear visualization of organelles. Large secretion granules are located in the main secretion mass, near the syncytium. In the compressed parotid gland, the myoepithelium shows a number of alterations, including presence of myelin figures and foci of degradation in the cytoplasm. The organelles of the syncytial cytoplasm are easily observed. The mitochondria are swollen; the cristae are shortened or absent. Syncytial secretion granules and lengthened structures linked to the syncytial matrix are to be seen. A large amount of smooth endoplasmic reticulum is present, while the rough endoplasmic reticulum is reduced. This large quantity of smooth endoplasmic reticulum suggests enhanced synthesis of the cardiotoxic steroids of the venom. Alterations in the mitochondria and the presence of myelin figures and degenerative foci in the cytoplasm may probably be regarded as consequences of the cellular injury provoked by compression. PMID- 1509493 TI - Synthesis and characterization of a disulfide bond isomer of omega-conotoxin GVIA. AB - Solid phase peptide synthesis and air oxidation of omega-conotoxin GVIA yielded, in addition to the desired product, an isomeric peptide which could be completely separated from the native toxin by repeated HPLC. A chymotrypsin-trypsin digest of this peptide, when subjected to HPLC peptide mapping, provided peptides identical with synthetic disulfide containing peptides predicted for the omega conotoxin isomer containing C1-C2, C3-C5, C4-C6 cystinyl pairings. The 'shaking' potency (ED50 = 1500 pmoles/kg, i.c.v.) of the isomeric peptide upon cannulated rats was 1.3% of the potency of native conotoxin (ED50 = 20 pmoles/kg). Considering that all three disulfide pairings in the isomer are different from the native toxin, its retention of biological activity is of interest. PMID- 1509494 TI - Renin and aldosterone levels and hypertension following envenomation in humans by the yellow scorpion Leiurus quinquestriatus. AB - Renin activity and aldosterone blood levels were measured in ten patients following scorpion envenomation by the scorpion Leiurus quinquestriatus. All patients were hypertensive on admission, with clinical signs of systemic intoxication. The blood renin and aldosterone levels were elevated in all ten patients. The observation of high blood pressure and elevated levels of renin suggests that in addition to increased circulating catecholamines following scorpion envenomation, sympathetically induced renin release may play an important role in the pathogenesis of hypertension. This observation re emphasizes the importance of afterload reduction in the treatment of the cardiovascular manifestations of scorpion envenomation. PMID- 1509495 TI - Fate of a single dose of the 14C-labelled mycotoxin, fumonisin B1, in rats. AB - The fate of the mycotoxin, fumonisin B1, (FB1) dosed to rats by i.p. injection and by gavage was traced using 14C-labelled FB1. Twenty-four hours after i.p. injection, 66% of the radioactivity was recovered in faeces, 32% in urine, 1% in liver and trace amounts (less than 1%) in kidney and red blood cells. When dosed by gavage, all (101%) radioactivity was recovered in faeces and trace amounts were found in urine, liver, kidney and red blood cells. The bulk of the radioactivity recovered was unmetabolized FB1. PMID- 1509497 TI - Effects of Duvernoy's gland secretions from the eastern hognose snake, Heterodon platirhinos, on smooth muscle and neuromuscular junction. AB - Duvernoy's gland secretions (100 micrograms/ml) from the eastern hognose snake, Heterodon platirhinos, induced a neuromuscular blockade in the isolated frog sciatic nerve-gastrocnemius muscle preparation and effectively antagonized acetylcholine and histamine responses of the rat duodenum preparation. The Duvernoy's secretions (100 micrograms/ml) produced a reversible, excitatory effect in the guinea-pig ileum in vitro. Mice administered the secretions (100 mg/kg, i.p.) exhibited minor, transient signs of toxicity. These preliminary observations provide evidence for toxicity of H. platirhinos Duvernoy's gland secretions but do not warrant categorizing the potential toxicity of this species with that of proteroglyphous, solenoglyphous, or the more venomous opisthoglyphous species. PMID- 1509496 TI - Structure of the low molecular weight protein copurified with alpha-latrotoxin. AB - Some samples of latrotoxin purified from the black widow spider venom contain two components: alpha-latrotoxin (M(r) approximately 130,000) and a low mol. wt protein with M(r) about 8000. Clones carrying the cDNA sequence for the low mol. wt protein copurified with alpha-latrotoxin were isolated from spider venom glands. Nucleotide sequence analysis of the cloned cDNA revealed the primary structure of the polypeptide to be 18 amino acids signal peptide and 70 amino acids protein chain with mol. wt of 7947 and pI of approximately 4.0. The protein exhibits certain structural homology with erabutoxin-a from the sea snake. PMID- 1509498 TI - What is tityustoxin? AB - Tityus serrulatus scorpion venom was fractionated by gel filtration affording two heterogeneous toxic fractions, T1 and T2; the latter was further fractionated by ion-exchange chromatography. The fraction of T2 eluted with 0.15 M ammonium acetate buffer, originally named 'tityustoxin', was shown to be a pool of several proteins. One of them, TsTX, as well as T1, was also named 'tityustoxin'. The major and perhaps most potent toxin of the venom, gamma-toxin, was eluted with 0.30 M buffer as a highly purified protein and shown to be different from TsTX. gamma-Toxin is contained in both T1 and T2. PMID- 1509500 TI - Bibliography of toxinology. PMID- 1509499 TI - Effect of the cyanobacterial (blue-green algal) toxins from Microcystis aeruginosa on isolated enterocytes from the chicken small intestine. AB - Livestock deaths, and clinical reports of human injury, follow the consumption of toxic blue-green algae. The experiments described show that isolated intestinal enterocytes from chicks are both deformed and killed by exposure to Microcystis toxins, in a dose-dependent and time-dependent manner. The enterocytes were protected from toxicity by deoxycholate, bromosulphothalein and rifampicin. It was concluded that the gastroenteritis clinically associated with accidental Microcystis ingestion is likely to reflect enterocyte injury by Microcystis toxins, and that the therapeutic use of bile acids or transport inhibitors may be of value in treatment. PMID- 1509501 TI - Effects of sea water pollution on chicken embryos. AB - Organic matter and heavy metal contamination in sea water obstruct vital functions of chicken embryos and interrupt their growth. Histological examination of contaminated fetuses showed a menacing growth of abnormal protuberances in the lungs as well as highly impeded formation of capillaries, although the windpipes exhibited normal expansion. Compared with controls, liver tissue also showed retarded growth accompanied by decrease in liver weight. Consequently, vital metabolic functions were impaired, hydropsy and evisceration developed, and fetuses were deformed. PMID- 1509502 TI - Evaluation of enzymuria as an indicator of amikacin-induced renal damage in guinea pigs. AB - Guinea pigs were injected subcutaneously for 10 days with amikacin (AK) at a dose of 0, 100, 200 or 400 mg/kg body wt. per day. The total daily dose was administered in either a single injection or divided equally and given as two daily injections. After the 10 days of AK treatment, uptake of the organic cation, tetraethylammonium (TEA) into renal cortical slices was inhibited in a dose-related manner. Changes in renal tubular morphology also increased with higher doses. The urinary excretion of the enzymes, N-acetyl-beta-D glucosaminidase (NAG), and alkaline phosphatase (ALP) significantly increased during the course of AK treatment, however, due to the large intragroup variability, the daily fluctuations and the absence of any distinct trends in urinary enzyme excretion it was difficult to establish a dose-relationship between AK-induced renal damage and the resultant enzymuria. At doses of 100 and 200 mg/kg body wt., the two-injection regimen resulted in the greater renal accumulation of AK and damage as reflected by a greater inhibition of TEA uptake and greater changes in renal tubular morphology. In contrast, this difference in toxicity could not be detected with enzymuria again due to the large intragroup variability and the absence of discernable excretion patterns of NAG and ALP. Thus, neither NAG nor ALP appear to be suitable quantitative markers of AK induced nephrotoxicity. PMID- 1509503 TI - Inhalation toxicity of chromium from Whetlerite dust in rats. AB - The acute inhalation toxicity and metabolic fate of chromium and copper from Whetlerite dust in rats were investigated. Groups of male and female, Sprague Dawley rats were exposed to Whetlerite dust and base carbon dust as outlined in the OECD Limit Test guidelines. At 14, 28 and 180 days post-exposure, rats were evaluated for gross pathological changes and tissues were collected for chromium and copper determination. Four deaths occurred during or post-exposure, but did not appear to be compound related. No gross pathological changes were observed at necropsy in either group. Organ chromium concentrations were below detection limits of 0.5 micrograms Cr/g dry tissue in both exposure groups. According to OECD guidelines, neither Whetlerite dust nor base carbon dust demonstrated an acute inhalation toxicity. PMID- 1509504 TI - Mesenteric mast cell degranulation in acute T-2 toxin poisoning. AB - T-2 toxin-induced alterations in rat mesenteric mast cell granulation were measured by cytophotometric analyses of the metachromatic reaction of mast cell granules with azure B. Hypogranulation (diminution of metachromatic material) was observed 8 h following injections of T-2 toxin (0.5-1.5 LD50, i.p.). These data suggest that mast cell activation occurs during acute T-2 intoxication and raise the possibility that mast cell mediators may contribute to toxin-induced cardiovascular collapse. PMID- 1509505 TI - Brain energy metabolites in mice intoxicated with acrylamide: effects of ischemia. AB - Concentrations of phosphocreatine, creatine, ATP, ADP, AMP, glucose and lactate in the whole brain did not differ between the mice intoxicated with acrylamide and the controls. When the brain was made ischemic, these concentrations changed to the same extent in both groups. The only difference was the lower pyruvate in acrylamide-intoxicated mice under the ischemia. Thus, as far as the whole brain is concerned, acrylamide does not cause gross alterations of energy metabolites, even under ischemia. PMID- 1509506 TI - Teratological assessment of diiodomethyl p-tolyl sulfone in rats. AB - Pregnant rats were given diiodomethyl p-tolyl sulfone (DIMPTS) at a dose of 0, 0.125, 0.25, 0.5 or 1.0% in the diet on days 6-15 of pregnancy. Maternal body weight gain and food consumption during the administration period were significantly lowered in the 0.25, 0.5 and 1.0% groups. No significant changes induced by DIMPTS were detected in the number of resorptions and dead fetuses, and body weight of live fetuses. Morphological examinations of fetuses revealed no evidence of teratogenesis. It could be concluded that DIMPTS has no teratogenic effects on rat offspring, even at doses which induced maternal toxicity. PMID- 1509507 TI - Detection of contact sensitivity of metal salts using the murine local lymph node assay. AB - The local lymph node assay (LLNA) is a predictive test for the detection of contact allergens. Nickel and chromium sensitization are common cases in man. However, in a previous study topical application of nickel sulfate and potassium dichromate in aqueous solution failed to induce activation in the draining lymph node. This study describes the application of LLNA to evaluate the contact sensitivity of metal salts. The metal salts were applied in dimethylsulfoxide or aqueous ethanol solution. In some experiments, the skin of the ears was gently abraded using a needle prior to application of metal salts. The ability of seven metal salts to induce lymph node cell (LNC) proliferation was compared. Nickel, cobalt, chromium and copper salts increased LNC proliferation, whereas zinc, manganese and iron salts failed to induce LNC proliferation in this assay. PMID- 1509508 TI - Modification by phenobarbital of decreased glutathione content and glutathione S transferase activity in livers of lead-treated mice. AB - Lead acetate (100 mg/kg) administered i.p. to male mice decreased hepatic glutathione (GSH) content and also glutathione S-transferase (GST) activity. However, the liver GSH content of mice treated with both lead and phenobarbital (80 mg/kg, i.p.) remained unchanged, whereas their GST activities were higher than the controls. Phenobarbital antagonized the Pb-induced decrease in liver adenosine triphosphate content. Additionally, phenobarbital shortened the half life of hepatic GSH determined using buthionine sulfoximine, an inhibitor of GSH synthesis. Acceleration of hepatic GSH turnover by phenobarbital possibly diminishes the Pb-induced impairment of GSH-conjugation of xenobiotics. PMID- 1509509 TI - Effect of cadmium and/or selenium on liver mitochondria and rough endoplasmic reticulum in the rat. AB - This study was conducted to investigate the effect of cadmium (Cd) and/or selenium (Se) on hepatic mitochondria and rough endoplasmic reticulum (RER). Male Sprague Dawley derived rats (150-200 g) received sodium acetate (NaAc; 1.23 mg/kg), Cd (0.84 mg/kg), and/or Se (1.6 mg/kg) intraperitoneally. Livers were perfused with 2% glutaraldehyde at 48 h, 72 h, or 96 h after treatment and prepared for electronmicroscopy. Results indicate that Cd and/or Se are capable of inflicting mitochondrial and RER structural changes, and the damage by Cd alone is more severe than Se alone or with Cd. PMID- 1509510 TI - Curvi-linear relation between acetone in breathing zone air and acetone in urine among workers exposed to acetone vapor. AB - An occupational health study was conducted on 45 acetone-exposed male workers in combination with 343 non-exposed men to examine the quantitative relationship between the intensity of acetone vapor exposure and the concentration of acetone in urine. The time-weighted average acetone concentrations were measured by means of diffusive samplers with water as absorbent, whereas urine samples were collected at the end of the shift as well as before the shift on the next morning. Acetone concentration in shift-end urine did not increase when the workers were exposed to acetone up to approx. 15 ppm, and this was followed by a gradual increase at a higher atmospheric acetone concentration, in a manner dependent to acetone vapor concentration. The comparison in acetone concentrations between the urine samples collected at the shift-end and those before the shift of the next morning showed that the levels in two sets of samples were the same among those exposed to 15 or less ppm acetone, whereas acetone in the shift-end samples was significantly higher than the counterpart levels in the pre-shift samples among those exposed to acetone at more than 15 ppm. PMID- 1509511 TI - Modification of metal-induced micronuclei formation in mouse bone marrow erythrocytes by Phyllanthus fruit extract and ascorbic acid. AB - The comparative efficacy of Phyllanthus emblica fruit extract, and its main constituent, ascorbic acid, in modifying the cytotoxic action of lead and aluminium was evaluated in vivo in bone marrow cells of Mus musculus. Oral administration of Phyllanthus emblica fruit extract for 7 days before exposure to the metals through intraperitoneal injections reduced the frequency of micronuclei induced by all doses of both metals. Priming with comparable doses of synthetic ascorbic acid reduced micronuclei formation induced by both doses of aluminium and only the lower dose of lead. With the higher dose of lead (20 mg/kg body wt.) priming with ascorbic acid increased the frequency of micronuclei when compared with mice administered lead alone. The greater efficacy of Phyllanthus fruit extract in alleviating metal-induced clastogenicity may be due to the combined action of all ingredients in the crude extract, rather than to ascorbic acid alone. PMID- 1509512 TI - Oxidative and non-oxidative metabolism of ethanol by the rabbit lung. AB - Pulmonary ethanol metabolism in the rabbit was investigated in vitro by examining oxidative (alcohol dehydrogenase) and non-oxidative (fatty acid ethyl ester synthase) pathways. Pulmonary alcohol dehydrogenase (ADH) activity was very low when measured at close to normal physiological conditions but increased at higher pH, although it was lower than that in the liver. Significant esterification of oleic acid was detected using rabbit lung homogenates, with the rate being intermediate to that of the other tissues examined. The results indicate that oxidative metabolism of ethanol (via ADH) by the rabbit lung is minimal compared to other tissues, but non-oxidative metabolism of ethanol leading to FAEE formation occurs at significant rates that may alter lipid metabolism or membrane composition. PMID- 1509513 TI - Sex variations. PMID- 1509514 TI - Detection of rare mRNAs via quantitative RT-PCR. PMID- 1509515 TI - Regulation of mitochondrial gene expression: transcription versus replication. PMID- 1509516 TI - Sex, light and carotenes: the development of Phycomyces. AB - Phycomyces blakesleeanus is known for the elaborate behaviour of its sporangiophores (fruiting bodies). Sporangiophore development is exquisitely sensitive to blue light, easy to describe quantitatively, pliable to genetic and biochemical research, and reminiscent in many details of other photoresponses in the same and in other organisms. The developmental and behavioural processes of Phycomyces share a number of genes. A combinatorial use of gene expression appears to be the basis for the complexities observed in this fungus. PMID- 1509517 TI - Cell polarity and cell diversification during early mouse embryogenesis. AB - At the eight-cell stage of mouse development, the organization of blastomeres changes from radially symmetrical to polarized. This acquisition of cell polarity, followed by asymmetric divisions, leads to the formation of two phenotypically different cell types, which give rise to the first two cell lineages of the mouse blastocyst embryo, trophectoderm and the inner cell mass. Cell fate, controlled by positional information, is not irreversibly fixed during differentiation, providing the embryo with considerable developmental flexibility. PMID- 1509518 TI - Continuous conversion of neuron phenotype in hydra. AB - All neurons in adult hydra are constantly changing their location. This poses interesting problems for the maintenance of the organization of the hydra nervous system. The solutions provide a different perspective on the development of nervous systems. PMID- 1509519 TI - The TATA-binding protein: a central role in transcription by RNA polymerases I, II and III. AB - The TATA-box-binding protein, first noted for its association with the general transcription factor TFIID, has recently been shown to be required for transcription by all three classes of nuclear RNA polymerase found in eukaryotes. As such, it plays a unique and pivotal role in gene expression in higher organisms. PMID- 1509520 TI - Microsatellites for linkage analysis of genetic traits. AB - Microsatellites are tandem repeats of simple sequence that occur abundantly and at random throughout most eukaryotic genomes. Since they are usually less than 100 bp long and are embedded in DNA with unique sequence, they can be amplified in vitro using the polymerase chain reaction. Microsatellites are easy to clone and characterize and display considerable polymorphism due to variation in the number of repeat units. This polymorphism is sufficiently stable to use in genetic analyses. Microsatellites are therefore ideal markers for constructing high-resolution genetic maps in order to identify susceptibility loci involved in common genetic diseases. PMID- 1509521 TI - K+ channel openers and 'natural' cardioprotection. PMID- 1509522 TI - Use of in vivo apparent pA2 analysis in assessment of opioid abuse liability. AB - Abuse liability testing of opioid drugs was originally motivated by attempts to separate the analgesic effects of opioids from their likelihood for abuse. It has become apparent that the human population group likely to abuse opioids has little overlap with the population group requiring opioids to treat pain, therefore there is no longer a need to separate these two properties of opioids. This is fortunate, since, as reviewed here by Jim Woods and colleagues, the results of the plethora of studies that have attempted to distinguish these two properties in known opioids strongly indicate that they are inseparable. Evaluation of the abuse potential of novel opioids remains, however, critically important in deciding on governmental restrictions on their accessibility. In addition, opioid abuse liability testing contributes enormously to our understanding of the behavioral mechanism of action of these drugs, and in surprising and helpful ways has increased our appreciation of the various test systems used to garner information about them. PMID- 1509523 TI - Cytokines and neuropathology. AB - Inflammatory processes in the brain require the cooperation of immunocompetent cells and glial cells, which communicate by secreting bidirectional mediators. Resident cells within the nervous system can synthesize and secrete inflammatory cytokines, as well as neuropeptides, contributing to the response within the CNS to injury or immunological challenge. Although the mechanisms of cell activation and immune interaction are poorly understood, accumulating evidence implicates these pathways in neuropathogenesis, as described here by Sharon Wahl and colleagues. For example, in the acquired immune deficiency syndrome (AIDS), HIV-1 induced nervous system dysfunction and dementia are associated with the presence of infiltrating leukocytes and the release of inflammatory cytokines. Defining the pathways of cytokine dysregulation and neurotoxicity invoked by the infiltrating leukocytes, as well as the contribution of the neural cells themselves, may help to identify mechanisms of intervention in this and other debilitating CNS diseases. PMID- 1509524 TI - IgG subclasses in symptomatic IgA deficiency. AB - We evaluated IgG subclass levels in 11 symptomatic patients (ages between 3 and 22; mean 7.5 years) with IgA deficiency, seven with selective IgA deficiency, and four with low IgA levels. All patients had experienced three or more episodes of sinopulmonary infections a year. Combined IgG2-IgG4 deficiency was detected in two patients, IgG2 deficiency in one patient and IgG4 deficiency in two patients. Elevated IgG1 and IgG3 levels were detected in most of the IgG subclass deficient and sufficient patients. It is known that gammaglobulin replacement therapy reduces the frequency of infections significantly in IgG subclass deficiency. Although immunization against IgA is a risk in IgA deficiency, these patients can be treated with gammaglobulins containing low IgA. PMID- 1509525 TI - Evaluation of the hypercoagulable state by measuring protein C and antithrombin III levels in nephrotic syndrome and in familial Mediterranean fever-related amyloidosis. AB - The levels of protein C (PC) and antithrombin III (AT III) antigens (ag) were measured in the plasma of 39 patients with various histologic types of primary nephrotic syndrome (NS) and in 12 patients with amyloidosis secondary to familial Mediterranean fever (FMF). The controls comprised 15 healthy children. Normal or elevated PC levels were observed in primary NS patients (mean 64%, range 36-98%) and in amyloidosis patients (mean 58%, range 48-70%). There was no difference found between PC ag levels in primary NS and in amyloidosis patients. In addition, no correlation existed between protein selectivity and the PC ag levels in the primary NS patients. Normal and decreased levels of AT III were observed (mean 29 mg/dl, range 11.1-39 mg/dl) in the patients with primary NS and amyloidosis (mean 31 mg/dl range, 21-39 mg/dl). The AT III ag levels of these two groups did not differ and no correlation was found between protein selectivity and AT III levels in primary NS patients. These results suggest that in patients with primary NS, or amyloidosis secondary to FMF, hypercoagulability is not related to a deficiency in PC ag levels due to a dynamic balance between urinary losses, increased rate of hepatic synthesis, catabolism and the distribution of PC in the body compartments. Patients with low AT III levels may be more susceptible to thromboembolic complications than patients with normal levels. PMID- 1509526 TI - Effects of cortisol and growth hormone on the metabolism of liver and bone in children with malnutrition. AB - A protein-energy deficit produces stress in the organism affecting all systems. Proportional to the degree of disease, cortisol and GH are mostly responsible for some of these effects. To investigate the effects on liver and bone, cortisol, GH, AST, ALT, ALP activities and Ca(T) and P(i) in serum were measured in 21 marasmus, nine kwashiorkor and 34 control children. In the marasmus group, we found a positive correlation between cortisol and AST, ALT and Ca(T) and a negative correlation between cortisol and ALP. In the kwashiorkor group there were positive correlations between the same parameters, although, they were of a lesser degree. Furthermore, in the kwashiorkor group we established a positive correlation between GH and ALP. Cortisol stimulates transaminases directly and suppresses ALP activity, thus indirectly increasing Ca(T), whereas GH has no direct effect on these enzymes. As the disease progresses and as liver functions deteriorate, AST, ALT and ALP increase in serum. PMID- 1509527 TI - Standard and low birth weight formulas compared for effects on growth of preterm infants. AB - The study population consisted of 22 infants hospitalized for low birth weight or prematurity at the Maternity and Children's Hospital in Samsun. Eleven infants were fed the low birth weight formula and the rest were fed the standard formula. Weight gain, increases in length and occipitofrontal circumference were higher in the low birth weight formula group than in the standard formula group. In cases which require it, a low birth weight formula should be given instead of the standard formula. PMID- 1509528 TI - A rare entity among childhood malignant lymphomas (large anaplastic T-cell Ki-1 +). AB - A case of peripheral type T-cell lymphoma is presented to underline the difficulty in distinguishing the initial clinical findings of an inflammatory neoplastic disorder since the diagnosis could only be arrived at after several repeated lymph node biopsies. An 11 10/12-year-old boy admitted to the hospital with inguinal lymph node enlargement was diagnosed as having adenitis and periadenitis. The disease had progressed and the patient had remittent fever rising to 39 degrees C, and another biopsy was taken. Cervical lymphadenomegaly was present, A diagnosis of chronic lymphadenitis with lymphocyte loss and fibrosis was established. The diagnosis could only be made from biopsy material taken from the deep cervical (jugularis interna) and axillary lymph nodes one year later, which showed Ki-1 antigen positive large T-cell lymphoma. The disease showed continuous activity in spite of chemotherapy and the child survived only 17 months. PMID- 1509529 TI - Beta-ketothiolase deficiency. A case report. AB - A four-month-old boy with beta-ketothiolase deficiency is described in this report. Presenting symptoms and signs were vomiting, irritability and acidotic respiration. Laboratory investigations revealed hyperglycinemia, metabolic acidosis and ketosis. Subsequent urinary GC-MS analysis of the patient's urine sample showed the typical pattern of beta-ketothiolase deficiency. Our experience with this case indicates that accurate diagnosis and early treatment of inborn errors might be lifesaving. PMID- 1509530 TI - Echocardiographic findings in endomyocardial fibrosis. AB - An 18-month-old infant diagnosed as having endomyocardial fibrosis by echocardiography is presented. Most patients with endomyocardial fibrosis reported in the literature are either older children or adults. To our knowledge, our patient was the youngest ever to have been reported. Echocardiographic studies showed obliteration of the left ventricular apex and increased echo reflectance at the left ventricular endocardium and subendocardium. The left atrium and right ventricle were significantly enlarged. Doppler echocardiography showed minimal mitral, but significant tricuspid regurgitation. In regard to the contribution of echocardiography in the diagnosis, we recommend this method for suspected cases. Contrary to the other patients reported, there was no thickening of the atrioventricular valves. Mitral valve insufficiency was related to the restriction of the ventricular filling rather than to valve involvement occurring with the disease. PMID- 1509531 TI - Immunofluorescence study of childhood renal amyloidosis. AB - In this paper, the findings of immunofluorescence (IF) studies of 57 patients with childhood biopsy-proven renal amyloidosis are presented. All specimens were investigated by the direct IF technique and the simultaneous use of antisera to human IgG, IgM, IgA, fibrinogen and C3. Antisera to C1q, C4, HbsAg, IgE (in each of ten cases), kappa and lambda light chains of immunoglobulins (Igs) and albumin (in each of five cases) were also used. AA type amyloidosis was determined in all patients by Wright's potassium permanganate reaction. In thirty-four of these patients (60%), Familial Mediterranean Fever (FMF) was found to be the underlying disease for renal amyloidosis. In 39 cases (68.5%), renal biopsy showed positive fluorescence staining while in 18 cases (31.5%), fluorescence staining was negative. The immunofluorescence pattern of glomerular deposits was neither granular nor linear but large isolated or confluent masses which were located in the mesangium and in the capillary walls, and were similar in all cases whatever the antisera used. The areas showing immunofluorescence staining almost corresponded to the locations of amyloid deposits. Immunoreactants showed various combinations of deposition with the exception of IgE, HbsAg and albumin antisera which yielded continuously negative reactions. C3 was the immunoreactant most commonly encountered. Kappa and lambda light chains of lgs were demonstrated in one of five biopsy specimens tested. Although it was not diagnostic, this IF pattern was found to be rather characteristic. Demonstration of immunoglobulins and other components of the humoral immune system is not a rare occurrence in renal amyloidosis, and passive absorption of plasma proteins does not simply explain these immunohistologic findings. PMID- 1509533 TI - [Does the new psychiatric law function?]. PMID- 1509532 TI - HLA and leukemia: is it a simple allelic association? AB - The first association between a disease and MHC antigens was established for viral leukemogenesis in mice. Since then, numerous studies in humans have been carried out and the data obtained suggest that Cw3 and Cw4 may be markers for leukemia susceptibility genes. Given the relatively weak relevance of HLA-C locus antigens in immune response, unrecognized properties of Cw3 and Cw4 should be considered to explain this association. Family studies have consistently revealed limited heterogeneity of HLA antigens in those families, increased parental HLA antigen sharing resulting in increased homozygosity among offspring and high frequency of recombinations within the MHC. Furthermore, the HLA genotype of leukemic patients was found more frequently among their siblings than the anticipated 25 percent. Another significant deviation from the Mendelian expectation was increased HLA-DR identity of offspring to that of their mother in those families. These and other observations imply that in leukemia families unknown MHC-linked recessive factors linked to Cw3 and Cw4 alleles may be susceptibility genes which also cause segregation distortion of HLA genes and probably developmental errors. PMID- 1509534 TI - [Use of compulsory measures in psychiatry after introduction of the new psychiatric law]. AB - Investigation of compulsory treatment and mechanical restraint in the Psychiatric Hospital in Arhus reveals that no great changes in the employment of compulsory measures in psychiatry during the period around introduction of the new Danish legislation on October 1 1989 have occurred. The total duration of mechanical restraint constituted 0.3% of the entire duration of psychiatric hospitalisation in acute admission wards after the introduction of the legislation. The mean duration of mechanical restraint was 4.3 hours (5 minutes-5.3 days) and was similar in men and women. In 55.5% of the cases of mechanical restraint, a waist belt alone was employed while, in the remaining cases, wrist or ankle cuffs were employed in addition. A doctor was present in 48.9% of the cases when mechanical restraint was applied. No differences were observed between the sexes in the extent of mechanical restraint but female patients were seen by a doctor prior to restraint more frequently than male patients. A tendency to employ a waist-belt alone was observed as the first form of restraint in women whereas men were frequently restrained by means of wrist or ankle cuffs also. The most frequent reason for restraint was that the patients constituted a danger to themselves and others. PMID- 1509535 TI - [Deprivation of liberty in psychiatry after introduction of the new psychiatric law]. AB - This investigation shows that the rate of commitment to mental hospitals in Denmark increased from the year before the introduction of the new Danish psychiatric legislation when it was 24.4 (23.1-25.8) per 100,000 of the population till the year after when it was 28.4 (27.0-29.9) of the population. The increase in the commitment rate may, wholly or partially, be the result of the fact that the deprivation of liberty, which was previously more or less informal, was now registered. The results do not suggest that commitment of non psychotic patients is employed more frequently than previously. The commitment rates for men and women were found to be identical after introduction of the new legislation. On the basis of data from the closed wards in the Psychiatric Hospital in Arhus, which receives approximately 11% of all committed patients in Denmark, it was found that the total number of admissions where patients were deprived of their liberty was nearly twice that of the number of involuntary admissions in the period immediately after introduction of the legislation. The average duration of involuntary detainment for committed patients was 20 days (1 101 days) and for patients admitted voluntarily but detained involuntarily 10 days (1-104 days). Involuntary detainment of patients admitted voluntarily occurred on an average two days (0-144 days) after admission. Following involuntary admission, significantly more women (51.5%) as compared with men (15.6%) were detained involuntarily whereas men had an excessive risk for deprivation of liberty for more than three days without formal involuntary detainment. PMID- 1509536 TI - [Compulsory measures in psychiatry. A review of the first year after introduction of the new law]. AB - A prospective survey of all registered treatment or measures carried out against the wishes of the patients during the first year after enforcement of the new Danish legislation in 1989 in the Psychiatric Hospital in Aalborg is presented. A total of 376 treatment situations and measures were registered. These involved 235 patients. It was found that 79 forced admissions had occurred together with 36 situations where patients who had been admitted voluntarily were forced to remain in hospital. The survey does not demonstrate any major change in the pattern of enforced measures and treatment after introduction of the new legislation. The working conditions for the new advisors for patients prescribed by the new law are described. These were found to be badly paid, idealistic and hard working. The daily administration of the law has been found to be quite bureaucratic. In addition, complains by patients concerning enforced measures and treatment are described. It is found that no verdicts contradict the steps taken by the hospital. PMID- 1509537 TI - [Compulsory admission for treatment--an interview study of patients. 1. Admission procedure, use of restraint and treatment]. AB - Forty-three patients committed for treatment in Copenhagen county were interviewed on their discharge from hospital. Half of the patients felt better after hospitalization, while one fourth of the patients were dissatisfied. Food, changes in housing and human contact were given as examples of the positive outcome. One half of the patients were given compulsory medication and one fourth were physically restrained. The patients experienced many adverse effects of the medication. It is recommended, that psychiatrists are involved to a higher degree in evaluation and treatment before decisions for compulsory hospitalization are taken. Investigations are needed to find predictors for a positive outcome in involuntary hospitalization. Unnecessary hospitalization should be avoided in order not to harm the patient-doctor relationship. PMID- 1509538 TI - [Compulsory admission for treatment--an interview study of patients. 2. Rights, guardianship and attitudes to commitment]. AB - Forty-three patients committed for treatment in Copenhagen County were interviewed about their rights, protection of rights and consequences of the commitment. Very few patients felt they had been properly informed about their rights and they knew very little about how to complain to the authorities about their commitment. Attorneys were found to have too little competence and insufficient training, and patients felt insecure about their attorneys' role. One forth of the patients agreed that they had to be committed, while one forth never accepted their commitment. Difficulties in giving information to the psychotic patient with disturbances in cognition and on unrealistic way of thinking are discussed. It is concluded, that there is a need to strengthen patients' rights, but not at the expense of the possibility of delay in administering treatment. PMID- 1509539 TI - [Compulsory admissions at the Frederiksberg hospital during the period 1 Nov 1987 to 30 Sep 1989. 1. Characteristics of the compulsory admissions and the admitted persons]. AB - During a period of 23 months from 1 Nov. 1987 to 30 Sep. 1989, before the new Danish legislation came into force, there were 64 compulsory commitments to the Psychiatric Department in Frederiksberg Hospital. These comprised 3.6% of all the admissions which corresponds to the national average in Denmark. Equally many were admitted on health grounds (yellow admission papers) and on account of danger (red admission papers). Women were admitted more frequently than men. The distribution corresponds to the sex distribution of all psychiatric admissions in Frederiksberg and reflects a sex distribution in the municipality with preponderance of women as compared with the national Danish average. On the Danish national basis, the majority of these admissions are men. One fourth of the admission papers did not contain an adequate description of the reasons for presuming mental illness and/or the danger or health criteria. There is thus reason to encourage meticulous care in completion of the medical certificates in cases of compulsory commitment. On discharge from hospital, 14% had a "non psychotic" diagnosis, which corresponds to the national Danish average. One month after discharge from hospital, 40% were attending outpatient treatment in the department and one year later, 38% of those followed-up were receiving outpatient treatment. In more than one third, compulsory commitment was thus followed by a prolonged period of voluntary treatment. 33% were readmitted during the subsequent year and this was compulsory in 13%. PMID- 1509540 TI - [Compulsory admissions at the Frederiksberg hospital during the period 1 November 1987 to 30 September 1989. 2. Patients' assessment and experiences of the admissions]. AB - The object of this prospective, descriptive investigation was to illustrate how the committed patients assessed and experienced the actual compulsory commitment and their assessment of the Danish legislation concerning mental illness by means of an interview investigation on discharge. During the period of investigation of 23 months, there were 64 compulsory admissions. Of these, 31 were on account of danger (red admission papers) and 33 on health grounds (yellow admission papers). Thirty-three (52%) patients were interviewed and of these 13 were admitted on account of danger and 20 on health grounds. Twenty-two (67%) of the patients did not realise that they were undergoing compulsory admission until the police came to fetch them. The majority considered that the functions of the police (68%), admission staff (55%) and the remainder of the staff (79%) had been good or satisfactory. 46% did not know who had demanded admission and did not ask the interviewer. 30% were satisfied with information about complaints. 42% were satisfied with the function of the supervisory committee but just under 30% did not realise that it existed. 61% considered that compulsory admission could have been avoided if other help had been offered. 61% were satisfied with the hospitalization. 64% considered that it is necessary to have legislation which permits compulsory admission. Relatively more of the patients admitted with red admission papers expressed satisfaction with, and accept of, their own compulsory admission and accept of compulsory admission in general. The present investigation will form a basis for comparison of the conditions under the new Danish legislation concerning mental illness. PMID- 1509542 TI - [Bilateral symmetrical stress fracture of the ulna]. AB - Good documentation is available concerning the prevalence, localisation and treatment of stress fractures. Stress fractures are much less common in the upper extremities than in the lower limbs. An unusual case of bilateral stress fractures in the ulnae in a patient aged 95 years is reported. These fractures are attributed to the use of a walking aid for a period of one year. The clinical features of stress fractures are discussed on the basis of the case history. PMID- 1509541 TI - [Acute uremia after renal cholesterol embolism]. AB - A case of acute uraemia caused by cholesterol emboli in the kidneys in a sixty six year old male with arteriosclerosis is presented. No effective treatment is available, but recognizing the condition may save the patient from otherwise time consuming extensive diagnostic programmes. PMID- 1509543 TI - [Penicillin allergy, look for the right one]. PMID- 1509544 TI - [Sleep apnea monitoring]. PMID- 1509545 TI - [Should pancreas transplantation still be used in Denmark?]. PMID- 1509546 TI - [Transplantation of pancreas and islet cells in insulin dependent diabetes mellitus--status after 25 years]. AB - The Danish study group for metabolic studies after transplantation of the pancreas. Development of combined pancreatic and renal transplantation and transplantation of islet cells in the treatment of insulin-dependent diabetes mellitus is reviewed. Transplantation of the pancreas is undertaken in Denmark on the indication of diabetes mellitus complicated by terminal diabetic nephropathy in patients who are considered, in advance, as candidates for renal transplantation. During recent years, improved results have been obtained by combined pancreatic renal transplantation with patient survival of up to 96% and graft survival of up to 84% after two years. Despite normal HbA1C, the intermediate metabolism is abnormal after combined pancreatic and renal transplantation. At present, it does not appear to prevent or arrest development of diabetic retinopathy while the results indicate that progression of diabetic nephropathy and neuropathy can be halted. Development in islet cell transplantation is promising. As yet, there has only been limited success with transplantation of foetal islet cells and this also involves great ethical problems. Xenographic transplantation of foetal islet cells may be of current value in the future. During recent years, 20% of islet cell transplantations from adult human donors have resulted in insulin independence for briefer periods (maximal 24 months, January 1992). Improved methods have been developed in immune modulation, immune isolation and cryopreservation and these make purification and harvesting of adequate quantities of islet cell mass possible to obtain exogenic insulin independence. Development of new immune suppressives has not improved the results. In the future, islet cell transplantation will possibly become part of the treatment of insulin-dependent diabetes mellitus. PMID- 1509547 TI - [Adjuvant treatment in connection with curative surgery of colorectal cancer]. PMID- 1509548 TI - [Aluminum allergy caused by DTP vaccine]. AB - All children referred to two private dermatological practices from 1 Jan. 1985 to 31 Dec. 1990 who had pruritus and subcutaneous infiltrates in the areas of immunization with Di-Te-Pol vaccine were patch tested with a Finn Chamber or with 2% aqueous aluminium chloride. Di-Te-Pol vaccine contains aluminium hydroxide. Contact allergy to aluminium was demonstrated in 32 children (20 girls and 12 boys). Of the three patch test methods used, testing with 2% AlCl3 occluded with a Finn Chamber proved to be the most sensitive. Immunization of children who have been shown to be allergic to aluminium should be carried out with vaccines which do not contain aluminium. PMID- 1509549 TI - [A comparison of the pattern of readmissions of long-term/geriatric patients and internal medicine patients]. AB - A comparison was undertaken between the frequencies of admission of medical patients over the age of 64 years and long-term/geriatric patients admitted to a large county hospital. The pattern of readmission is described in relation to the age groups and sex. The period of observation was nine months. In the investigation, the relationship between the distribution of men and women in the normal population was taken into consideration and a correction factor was calculated. A total of loll patients (CP) discharged from an acute medical department (AM) had 1954 readmissions (GI). In the long-term medical department (LMA) 158 CP had a total of 328-GI. The number of CP readmitted in each age group and sex reflects the representation of the group concerned in the background population, although a tendency was observed for slightly more admissions, the older the CP were. No difference in the pattern of readmission was observed concerning CP readmitted from AM and readmitted to all departments including AM. Similarly, despite some scatter, there was no difference in the GI pattern in CP discharged from LMA and readmitted to all departments including LMA. In addition, no significant difference in the GI pattern was observed as compared with the AM patient group and the LMA patient group. As patients referred to LMA have, quite naturally, poorer performance than the patients who were discharged directly from medical or surgical departments, it may be concluded that, after treatment in LMA, no difference between the patient groups was found if the GI frequency was taken as a yardstick. As GI, just as other measurements of turnover, only provides an expression of the status at a given moment, the author considers that it is of importance both for the departmental and the political planning that the GI frequency is followed as part of the current assessment. PMID- 1509550 TI - [The dosage-effect-curves for propofol in young and elderly patients--and modification of these following fentanyl]. AB - Forty-eight patients between 20 and 40 years and 48 patients between 60 and 80 years, none of whom had received premedication were subdivided at random for induction of anaesthesia with propofol (Diprivan) in four doses with or without prior administration of fentanyl. ED95 (effective dosage for 95%) for the young patients was 3.4 mg/kg and, for the elderly patients, 2.4 mg/kg. When 4 micrograms/kg fentanyl was administered five minutes prior to induction of anaesthesia, ED95 was reduced by 10% in the young patients and 20% in the elderly patients. In both the young patients and the elderly patients, the mean arterial blood pressure (MAP) three minutes after induction was found to be reduced by 2 26%. No further reduction was observed. The pulse did not alter significantly from the original value. When 4 micrograms/kg of fentanyl was administered five minutes prior to induction of anaesthesia, a significantly more pronounced decrease in MAP was found in young and also elderly patients during the entire period. This decrease in MAP was dependent on the dosage in the group of elderly patients. During the period of investigation, the pulse decreased 5-35%, except in the group of the young patients who received the smallest doses of propofol, where an increase of 15-20% was observed. It is concluded that induction of anaesthesia with propofol preceded by administration of fentanyl, may be followed by a considerable reduction in MAP. PMID- 1509551 TI - [Chronic recurrent multifocal osteomyelitis]. AB - A case of chronic recurrent osteomyelitis (CRMO) in a girl aged ten years is presented. This is an unusual inflammatory process which involves multiple osseous sites recurrently. The symptoms are insidious pain in the limbs associated with fever and, occasionally, pustulosis palmoplantaris. The disease is characterized by recurrent exacerbations but is self-limiting. Complete investigation including bone biopsy should be carried out for differential diagnostic reasons but repeated invasive investigations and repeated antibiotic treatment should be avoided on recognition of the disease. No consistent laboratory findings, apart from raised erythrocyte sedimentation rate, are found. PMID- 1509552 TI - [Pathological gambling]. AB - The case of a patient with a pathological urge to gamble is presented. Until 1990, gambling casinos were prohibited in Denmark. In 1990, a new law was enforced which permitted six casinos in Denmark. Previously, no reports were available in the medical literature concerning pathological gambling in Denmark. The incidence of pathological gambling will probably increase as a consequence of the new law. PMID- 1509553 TI - [The slimming effect of ephedrine]. PMID- 1509555 TI - [Nephrotic syndrome--better therapeutic possibilities]. PMID- 1509554 TI - [Liposuction in adiposis dolorosa (morbus Dercum)--an effective therapy]. PMID- 1509556 TI - [Cyclosporin A treatment of adult patients with severe nephrotic syndrome]. AB - This investigation is an assessment of the cyclosporin A-prednisone treatment which has been employed in all cases of therapy-resistant nephrotic syndrome in adults (n = 18) since January 1985 at the Department of Nephrology at the State University Hospital. Following an average duration of treatment of 20.7 months, five patients were in complete and eight in partial remission. All of the patients with minimal change disease (three patients) achieved complete remission. Recurrence after withdrawal of cyclosporin A occurred in three out of five patients. Cyclosporin A was withdrawn in five patients on account of suspected cyclosporin A nephrotoxicity. Hypertension, which was slight to moderate in the majority of cases, occurred frequently during treatment. Compared with the prognosis and frequency of complications in the untreated nephrotic syndrome and the frequency of side effects with the previously administered immunosuppressive treatment, the frequency of side effects with cyclosporin A treatment was acceptable. Until the indications are elucidated, adult patients with otherwise intractable nephrotic syndrome should be referred to special nephrological departments for possible cyclosporin A treatment. PMID- 1509557 TI - [Malignant melanoma of the skin in Denmark--epidemiology, diagnosis and treatment]. AB - About 700 new cases of malignant melanoma of the skin are registered annually in Denmark. The incidence is increasing rapidly and the number of new cases increases by more than 5% per annum. The most important phenotypical risk factors are the number of acquired pigmented naevi and exposure to sunlight is the most important risk factor in the external environment so that severe sunburn in children and intermittent intense exposure to sunlight increase the risk of melanoma. The thickness of the tumour at the time of the diagnosis is the most important prognostic factor. The prognosis deteriorates with increasing thickness. Treatment is primarily surgical. In cases of inoperable local melanoma and regional recurrences, irradiation may be administered. Chemotherapy and/or immunotherapy are of experimental character. In the light of the rapidly increasing incidence, it is important that knowledge of risk factors for development of the disease and the clinical characteristics of early melanoma is spread to not only the medical profession but also to the general public. PMID- 1509558 TI - [Intraoperative complications during cementation of hip arthroplasty. Avoiding air embolization during cementation]. AB - Circulatory collapse is known to occur during cementation of hip arthroplasty. The pathogenesis is multifarious, but the most important cause is believed to be formation of air embolism during insertion and cementation of the femoral component followed by air embolism in the heart. Inserting the cement retrogradely with a cement gun following distal plugging of the femoral cavity with spongiosa and using a plastic catheter for suction drainage reduces the air embolisation. Cement producing as little heat as possible during the setting should be used. Maintaining anaesthesia with N2O air embolism and should be avoided during and after cementation. Pre- and intraoperative care of the patient's circulation and oxygenation is essential. The use of pulse oximetry, capnography and precordially recorded Doppler ultrasound are recommended for monitoring air embolism. PMID- 1509559 TI - [Antibiotic prophylaxis in lung surgery. A review]. AB - The most important postoperative infections in general pulmonary surgery are empyema, pneumonia and wound infection. Risk factors are underlying malignant disease and the duration of the operation. The extent of pulmonary resection also appears to be of a certain significance. Five prospective randomized, double blind, placebo-controlled investigations are available. Together, these investigations demonstrate that prophylactic antibiotic treatment, in which the first dose is administered immediately prior to operation, reduces the frequency of pneumonia (from 27% to 17%) and the frequency of wound infection (from 18% to 4%). Despite antibiotic prophylaxis, empyema occurs with frequency of 3%. Prophylactic antibiotic treatment has also reduced the duration of hospitalization and the postoperative employment of antibiotics. The relatively few comparative investigations have not indicated unanimously that any particular antibiotic was more advantageous than other. At present, we have insufficient knowledge about the pathogenesis of the above mentioned postoperative infections. Such knowledge could increase the possibility of other prophylatic measures. PMID- 1509560 TI - [Primary aneurysmal bone cyst. Evaluation of the symptomatology, treatment and prognosis based on 21 patients]. AB - PABC is a rather rare, non-malignant osteolytic bone disease, affecting children and young people. Most frequently, it is localized to the metaphyses of the long bones. The present material consists of 21 cases, treated in the Orthopaedic Hospital in Aarhus between 1973 and 1991. Nineteen patients were treated with curettage of the cyst followed by bone grafting to the cavity. Six (31%) had recurrences. Five were operated again without any recurrence. The last patient has not yet received any further treatment. Two patients were initially treated by bone resection. No postoperative complications occurred. Curettage of PABC followed by bone grafting is recommended as the treatment of choice, in spite of the recurrence rate mentioned above. Because of the risk of recurrence after this treatment, regular follow-up examinations are necessary until healing has occurred i order to treat a possible local recurrence in time. PMID- 1509561 TI - [Hypertrophic obstructive cardiomyopathy complicated with bacterial endocarditis]. AB - A patient with hypertrophic obstructive cardiomyopathy (HOCM) and Staphylococcus aureus mitral valve endocarditis is reported. Bacterial endocarditis occurs with increased frequency and the prognosis is worse in these patients. All patients with HOCM should therefore be given antibiotic treatment every time they undergo invasive procedures to prevent potentially fatal bacteraemia. PMID- 1509562 TI - [Antibiotic prevention of endocarditis. A reference program for physicians and dentists]. PMID- 1509563 TI - [Duty of physicians to establish and present the diagnosis of disseminated sclerosis]. PMID- 1509564 TI - [Changes in mental function after anesthesia and surgery]. AB - Minor short-term depression of mental function is seen after anaesthesia and surgery. However, general anaesthesia does not seem to cause permanent damage or depress mental function beyond the first 2-4 postoperative days and no significant advantages of regional anaesthesia, as regards to cerebral function, are found after this period. Severe cases of long term mental deterioration after surgery and anaesthesia may be explained by other factors such as per- and postoperative complications. The risk of mental disturbance is increased in patients with psychiatric disease or presenile dementia and may be due to ongoing treatment with tricyclic antidepressant and neuroleptic drugs. Centrally acting cholinergic drugs, hypotension and hypoxia together with postoperative pain and sleep deprivation should be avoided. PMID- 1509565 TI - [Pneumomediastinum]. AB - Pneumomediastinum is a rare pathological condition with air in the mediastinum outside the trachea and oesophagus. The etiology may be spontaneous/resulting from exertion, traumatic, iatrogenic or it may be due to inflammation, neoplasm or perforation of a hollow abdominal organ. In pneumomediastinum resulting from exertion, a pressure gradient occurs and this causes rupture of marginally situated pulmonary alveoli. Air escapes from the alveoli into the perivascular adventitia and dissects its way along the vessels to the mediastinum. The commonest symptoms are pain in the thorax in 80-90% of the patients, followed by sensation of oppression and dysphagia. Stethoscopic examination reveals crepitation synchronous with pulse and respiration in half of the cases. The diagnosis is verified by radiographic examination of the thorax where air can be seen as vertical radio-translucent regions in the mediastinum and along the borders of the heart. Patients with pneumomediastinum should be admitted to hospital for investigation as treatment of a possible basic condition, e.g. rupture of the oesophagus or bronchus, is important. In uncomplicated cases, the mediastinal emphysema disappears in the course of a week. Mediastinotomy with incisions for relief of pressure may prove necessary. PMID- 1509566 TI - [Duration of immunity and occurrence of secondary vaccine failure following vaccination against measles, mumps and rubella]. AB - The present article illustrates the extent of secondary vaccine failure after vaccination for measles, mumps and rubella (MMR). Secondary vaccine failure means loss of the immunity induced by vaccination to such an extent that infection becomes possible. Serological investigations carried out with follow-up periods of up to 16 years after vaccination for measles, 21 years after vaccination for rubella and 12 years after vaccination for mumps reveal that loss of antibodies occurs with the elapse of time but that the clinical significance of this is probably very limited. Where all three types of vaccination are concerned, secondary vaccine failure has hitherto been very seldom. Infection with measles after secondary vaccine failure is generally described as running a milder course. In rare cases, rubella re-infection has resulted in infection in utero, so that a slight risk of congenital rubella cannot be entirely excluded after successful vaccination. No extensive systematic investigations of the effect of revaccination have been carried out and, similarly, the optimal interval between two or more vaccinations has not been illustrated in more detail in the literature. Subclinical infection is not uncommon after all three vaccines. Where measles is concerned, immunity may possibly be regarded as a continuum which, depending upon the antibody level, protects the individual from various degrees of clinical disease. If wild virus can be spread via individuals with subclinical infections, it is doubtful whether population immunity (herd immunity), which is necessary to eliminate the three diseases, can be attained in large populations.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1509567 TI - [Changes in measles, mumps and rubella (MMR) immunity until the year of 2002 after the introduction of MMR vaccination]. AB - In order to decide whether vaccination for measles, mumps and rubella should be introduced at the age of five years, calculations of the immunities in various age groups were performed until the year 2002 with and without vaccination at the age of five years. These calculations are based on the knowledge of immunity in the various age groups before the MMR vaccination programme was instituted in 1987 and knowledge of the compliance with vaccination obtained to date. Future predictions reveal that it is of decisive significance that compliance with vaccination among 12-year-olds is increased as rapidly as possible to 0.7 and to 0.8 in the subsequent year, if the level of immunity present prior to institution of the vaccination programme is to be maintained. The second vaccination given at a shorter interval after the first would prevent about 150 cases of illness in all per annum among 6-12 years-old. However, this should not be introduced at the expense of vaccination at the age of 12 years, which should be continued for at least 10-15 years yet. Possible abandoning of vaccination at the age of 12 years 10-15 years hence presupposes that adequate numbers of the children have been vaccinated twice at an early age and that it is sufficiently certain that secondary failure of vaccination does not occur to any significant extent. PMID- 1509568 TI - [Clinical picture of acute pulmonary embolism. Relations to the degree of vascular obstruction]. AB - In 132 consecutive patients treated for pulmonary embolism, duration of symptoms, number of embolic episodes before the diagnosis, circulatory affection (stable circulation (n = 61), reversible shock (n = 60), circulatory collapse (n = 11), electrocardiographic findings and systolic pulmonary pressure (n = 60) were analysed in relation to 1) underlying diseases (orthopedic surgical patients (n = 43), gynecological-abdominal surgical patients (n = 22), preembolic healthy patients (n = 42), miscellaneous medical patients (n = 25)), and 2) the obstruction of the pulmonary vascular bed quantified by a scintigraphic or angiographic score. While embolic score did not differ between the groups of underlying diseases, preembolic healthy patients with deep vein trombosis (n = 30) had longer mean duration of symptoms (14 days), more embolic episodes, (1.7 episode) and higher pulmonary pressure (72 mmHg) than the material on an average with values of 7 days, 0.9 episodes and 57 mmHg, respectively (p less than 0.001). Among patients with reversible shock or circulatory collapse, half had at least one previous embolic episode, one fifth from two to four. Embolic score correlated well with the circulatory affection (p less than 0.001). A high pulmonary pressure correlated with long duration of symptoms and a high number of embolic episodes (p less than 0.002). Sinus tachycardia and electrocardiographic signs of acute right ventricular strain (complete and incomplete right bundle branch block, SIQIIITIII-pattern and inverted T-waves in V2-4) correlated positively to the circulatory affection and inversely to duration of symptoms and number of embolic episodes (p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1509569 TI - [Aggressive treatment of acute pulmonary embolism. 132 consecutive patients treated with heparin, streptokinase or embolectomy, 1975-1987]. AB - During 1975-1987, 132 patients were treated for acute pulmonary embolism with heparin (n = 41), streptokinase (n = 52), or embolectomy (n = 39). In 1984, the indications for embolectomy were broadened to include all patients with central emboli, also those who were circulatory stable. The heparin-, streptokinase-, and embolectomy groups differed from each other as regards the degree of circulatory impairment (stable circulation/reversible shock/circulatory collapse: 68/32/0% versus 52/48/0% versus 16/56/28%, p less than 0.0001) and embolic score (20 for complete obstruction; 5.6 +/- 3.4 versus 8.7 +/- 2.8 versus 13.2 +/- 2.4, p less than 0.0001), but were comparable in terms of prognosis (30-day mortality/10-year survival +/- standard error: 7%/61 +/- 9% versus 13%/59 +/- 9% versus 18%/61 +/- 10%). Stable circulation, reversible shock, and circulatory collapse prior to embolectomy resulted in 30-day mortalities of 0%, 9%, and 45% respectively (p less than 0.01). During 1984-1987, no early or late deaths after embolectomy were observed in patients without circulatory collapse (n = 10). In comparable patients (embolic score greater than or equal to 9, symptom duration less than or equal to 7 days, no circulatory collapse), streptokinase treatment (n = 13) and embolectomy (n = 25) resulted in 10-year survival +/- standard error of 46 +/- 16% and 82 +/- 10% respectively (p less than 0.0001) and in an embolic score reduction (score before minus score after treatment) of 5.7 +/- 2.3 and 10.5 +/- 2.9, respectively (p less than 0.0001). Embolectomy during extracorporeal circulation should be considered the treatment-of-choice in patients with acute central emboli. PMID- 1509570 TI - [Extracardiac rhabdomyomas]. AB - Two cases of extracardial rhabdomyomata are described. One case was discovered incidentally at autopsy while the other was primarily examined by needle aspiration biopsy. As far as the authors are aware, this is the first case to be reported. PMID- 1509571 TI - [Acute vasculitis and arthritis caused by Parvovirus B 19 infection]. AB - A 35-year old woman was admitted with fever, polyarthritis and severe vasculitis. The symptoms resolved spontaneously within a week. Two weeks later, her seven year old son developed erythema on arms and legs and the typical "slapped cheek syndrome" characteristic of erythema infectiosum. Both cases were due to acute infection with Parvovirus B 19 as demonstrated by the presence of IgM-antibodies to Parvovirus B 19. The cases are described in order to draw attention to the possibility of Parvovirus B 19 infection as the etiological agent for acute vasculitis in adults. PMID- 1509572 TI - [Capnometry]. PMID- 1509573 TI - [Surgery of penile deviation by Ebbehoj's methods]. PMID- 1509574 TI - [Intensive therapy and its value]. PMID- 1509575 TI - [Reflex dystrophy]. PMID- 1509576 TI - [Necrobacillosis]. AB - Necrobacillosis is an infection caused by the anaerobic Gram-negative rod Fusobacterium necrophorum. The infection is most common in previously healthy young adults and is characterised by sore throat followed by rigors, septicaemia and the formation of metastatic abscesses, often in the lungs. The infection has a certain mortality, which is reduced when early and sufficient treatment is administered. The treatment is a prolonged course of penicillin and/or metronidazole. Two case histories and a review of the literature are presented. The purpose of this article is to make the clinician aware of the syndrome, which is so characteristic that the diagnosis can be made from the clinical picture alone before bacteriological verification. PMID- 1509577 TI - [Foot zone therapy and bronchial asthma--a controlled clinical trial]. AB - Thirty patients with proved bronchial asthma receiving treatment with inhaled steroid in dosages of less than 1,000 micrograms daily were subdivided at random into two groups of 15 patients. One group received foot zone therapy and the other merely uniform clinical care but without "placebo foot zone therapy". The "active" group received a total of ten foot zone therapy sessions of one hour at intervals of one week. The asthmatic symptoms, consumption of medicine and the objective pulmonary function parameters were followed-up during the subsequent six months. Decrease in consumption of beta-2-agonists and increase in peak-flow levels were observed in the group which had received foot zone therapy, but the same changes were observed in the control group. The authors do not find that this investigation demonstrates that foot zone therapy is of effect on the disease bronchial asthma. They conclude, however, that the favourable effect in both of the groups are due to increased care and control which occurred in both patient groups. PMID- 1509578 TI - [Clinical trial of 2 highly sensitive pregnancy tests--Tandem ICON HCG-urine and OPCO One-step Pacific Biotech]. AB - The highly sensitive pregnancy test, Tandem ICON HCG-urine, was compared with OPCO "One-step" Pacific Biotech in the gynecological and obstetrical department of Randers Hospital. The purpose was to determine the test specificity and sensitivity of the pregnancy tests in women with possible pregnancies. The test sensitivities were found to be 0.83 and 0.63 for ICON and ONE, respectively. We experienced one and four cases of negative pregnancy tests and ectopic pregnancies with ICON and ONE, respectively. In all cases, the diagnosis of ectopic pregnancy was suspected by other means and the patients submitted to operation. The ICON test showed its supremacy in diagnosis while ONE was easier and cheaper. PMID- 1509580 TI - [PermCath as intravenous access in chronic hemodialysis]. AB - PermCath is a dual-lumen silicone catheter for permanent venous access for hemodialysis. During an observation period from 1 July 1988 to 30 June 1991, 49 PermCath were inserted in 32 patients. In 24 patients (75%), the PermCath was used as sole method of access for hemodialysis through the observation period. Six of the 24 patients required changing of the catheter once, and in three patients the PermCath functioned properly only after the third insertion of a PermCath. In eight patients, vascular access could not be accomplished using the PermCath and these patients were all hemodialyzed through another vascular access. Four patients developed bacteraemia and one patient developed thrombosis of the subclavian vein during the observation period. Insertion of the PermCath is easy and, in case of malfunction, changing or removal of the catheter is easily accomplished. The PermCath is recommended as an alternative to existing techniques for intravenous access for hemodialysis. PMID- 1509579 TI - [Elimination of human chorionic gonadotropin in serum and urine after uncomplicated induced abortion during the first trimester]. AB - Serum chorion gonadotropin was measured weekly in 12 women from the time of legal first trimester abortion until values were below 10 IU/L. The elimination followed a 2-component curve. The half-life in the first few days was 1.1 day, hereafter 4.2 days. Serum-HCG decreased to less than 10 IU/L within 22 to 40 days. The elimination of serum-HCG was found to decrease so uniformly, that values which do not decrease must be considered abnormal. A sensitive bedside urine-HCG test was found to be positive from 13 to 31 days after the abortion. PMID- 1509582 TI - [Non-surgical treatment of acute cholecystitis in high-risk patients. Percutaneous drainage of the gallbladder and removal of stones]. AB - Eight high-risk patients with acute cholecystitis were submitted to subhepatic percutaneous drainage of the gall-bladder as the initial treatment. One patient died a few days after the intervention. Six patients had stones in the gall bladder. Cholecystectomy was performed in one of these in five, the stones were removed by a percutaneous endoscopic technique after dilatation of the drainage canal. No noteworthy complications occurred. PMID- 1509581 TI - [Routine coronary arteriography in younger patients with acute myocardial infarction]. AB - Coronary arteriography was performed in 50 patients aged 40 years of less all of whom had had acute myocardial infarction (AMI). Forty-seven patients had at least one risk factor for development of ischaemic cardiac disease. Smoking and familial predisposition were the commonest predisposing factors. Seventeen patients had stenosis in a single coronary artery only. Six patients had three vessel disease and none had stenosis of the main stem of the left coronary artery. Eight patients had no stenoses. All patients with three-vessel disease had sign of ischaemia after infarction. The type of infarction was related to the number of stenosed vessels, so that patients with Q-wave infarction had a greater number of stenoses than patients with non-Q-wave infarcts. A congenital coronary in the form of abnormal origin of the left coronary artery from the pulmonary artery was the cause of AMI in an isolated case. On the basis of this retrospective investigation, the authors have assessed the value of routine coronary arteriography (CAG) in 50 relatively young patients who had recently sustained AMI. CAG does not appear to be indicated as a routine procedure in all of these patients but could have been performed primarily on the basis of symptoms or the findings from non-invasive investigations. PMID- 1509583 TI - [Ultrasonically guided Biopty-biopsy of focal liver processes]. AB - During a period of three years, 51 patients with focal hepatic changes were submitted to 55 ultrasonically guided Biopty-biopsies. Histological diagnoses could be established in 45 patients at the first biopsy which corresponds to a diagnostic certainty of 88.2% Histological diagnoses were established in 49 patients which corresponds to a certainty of 96%. The frequency of complications was 3.9%. Biopty-biopsy is recommended as a good method because it is easy to carry out and provides just as good results as other methods of biopsy. In addition, it can provide more histological information than aspiration biopsies which are, however, somewhat cheaper. PMID- 1509584 TI - [Parenchymal pulmonary endometriosis]. PMID- 1509585 TI - [Vaginitis emphysematosa]. AB - Vaginitis emphysematosa is a benign, uncommon condition characterised by the presence of gas-filled cysts beneath the vaginal epithelium. Cases has been reported in pregnant women, in patients with diseases of the cardiovascular system and in patients with Trichomonas or Gardnerella vaginitis. To date the etiology and pathogenesis have not been fully elucidated. A case of vaginitis emphysematosa in a patient with cardiovascular disease is described. PMID- 1509586 TI - [Subjects participating in experiments involving exposure to ionizing radiation. Central Scientific Committee]. PMID- 1509587 TI - [Births in Denmark 1990]. PMID- 1509588 TI - [Physician's role in misinformation about nutrition]. PMID- 1509589 TI - [Amantadine in influenza]. PMID- 1509590 TI - [Ketamine]. PMID- 1509591 TI - [Ketamine. A controversial anesthetic agent]. AB - On the basis of a review of the literature, a survey is presented concerning the controversial anaesthetic agent ketamine, its pharmacology, mechanism of action and employment. Particular emphasis is placed on the cerebral, cardiovascular and pulmonary effects and the clinical employment. Similarly, the side effects and their prophylaxis are described. It is concluded that ketamine is considered to be a valuable preparation which can be employed both in and outside hospital. PMID- 1509592 TI - [Ketamine as a broncholytic agent in status asthmaticus and as an anesthetic for patients with bronchial asthma]. AB - Ketamine was introduced into clinical anaesthesia in 1965. Since then it has been demonstrated to lower airway resistance and to increase lung compliance in the asthmatic patient. It has also proved useful in anesthetizing asthmatic patients with or without symptoms. In several case reports it has been used successfully in the management of status asthmaticus resistant to conventional therapy but so far no controlled clinical trial has been carried out to support this empirical use of ketamine. The limited magnitude of the side effects permits the use in status asthmaticus when all other treatment has failed. Experiments with animals and with human preparations have suggested one or more of the following mechanisms of action: a sympathomimetic effect, a direct relaxant effect, an antagonism to histamine and acetylcholine and a membrane stabilizing effect as with local analgesics. Until investigations have been published ketamine is recommended as an anaesthetic for the asthmatic patient and for the patient who has previously reacted with bronchospasm when intubated or anaesthetized. Prospective clinical trials should be planned. PMID- 1509594 TI - [Morbidity of children attending day care centers in Copenhagen illustrated by social, physical, environmental and hygienic factors]. AB - Sick leave among the children in 24 day nurseries in Copenhagen was registered during a period of one year. The physical, environmental and hygienic conditions of the institutions were assessed by means of interviews and inspection, supplemented by information from the local authorities. Sick leave constitutes 7.5% of the days during which the institutions were open and the average number of sick days per child varied from 14.6 to 24.4. Comparisons with similar investigations are inclusive on account of variations in the methods of registration and age distributions. It was characteristic of the institutions investigated that these included a number of old institutions in flats, many in streets with considerable traffic and where the conditions of ventilation and space do not conform with present-day standards. In some of the institutions, the hygiene is unsatisfactory, particularly where ventilation, outdoor activities and hand-washing are concerned. A statistically significant connection was found between amount of traffic at the institution, the hygiene and playroom area per child, on one hand, and absence due to sickness, on the other, as assessed by a statistical model for sick leave for child in a given institution. In order to prevent sickness, it is concluded that efforts to improve hygiene and space are desirable and, similarly, further research concerning the effects of atmospheric pollution is relevant. PMID- 1509593 TI - [Surfactant treatment of newborn infants with respiratory distress syndrome primarily treated with nasal continuous positive air pressure. A pilot study]. AB - In this pilot study, Curosurf (200 mg/kg) was administrated to 34 patients with the respiratory distress syndrome in nasal-CPAP therapy with FiO2 requirements greater than 0.60 and/or TcPCO2 greater than 8 kPa. The surfactant was instilled during a short period of intubation or in a few cases via an intratracheal catheter (Ch. 6). The age of the patients on surfactant treatment ranged from two to 72 hours. Eighteen patients could be maintained on nasal-CPAP after treatment with Curosurf and only a few complications were seen in these infants. The other 16 patients subsequently required artificial ventilation and had a higher incidence of pulmonary and extrapulmonary complications. On the basis of these observations, we plan a randomized trial to investigate whether, administration of surfactant reduces the need for ventilator treatment and improves the odds for uneventful recovery in this category of patients. PMID- 1509595 TI - [Obsessive-compulsive disorders in children and adolescents. Phenomenological aspects]. PMID- 1509596 TI - [Acute hemorrhoidectomy compared with incision and McGivney's ligature in the treatment of incarcerated hemorrhoids]. PMID- 1509597 TI - [Anorectal pressure gradient in patients with anal incontinence]. PMID- 1509598 TI - [Ondine's syndrome (alveolar hypoventilation)]. AB - Ondine's syndrome is a rare condition characterised by alveolar hypoventilation during sleep on account of an abnormality in the automatic control of respiration. The respiration centre does not react adequately to the carbon dioxide tension in the blood required to maintain normal ventilation. We present a description of the course in an infant with congenital Ondine's syndrome because a therapeutic possibility is now available, viz, implantation of a phrenic nerve pacemaker. The infants showed respiratory insufficiency shortly after delivery. This disappeared on tactile stimulation. The infant had generalised hypotonia with absent patellar reflexes and weak sucking reflexes and, at the age of one week, seizures developed. The infant was treated with assisted ventilation but this could be reduced to use only during the period when the infant slept. The infant was in good health with normal psychomotor development until the age of two years. Plans had been made to implant a phrenic nerve pacemaker. Unfortunately, the infant developed Syncytial-virus pneumonia complicated by bacterial superinfection and developed severe anoxic brain damage which subsequently proved fatal. PMID- 1509599 TI - [Hip joint surgery in Alborg]. PMID- 1509600 TI - [Guidance or manipulation?]. PMID- 1509601 TI - [Breast prostheses and scleroderma]. PMID- 1509602 TI - [Hematological abnormalities in alcoholism]. AB - The most common haematological abnormalities in alcoholism are raised mean corpuscular volume of the erythrocytes and thrombocytopenia. The etiology is multifactorial including malnutrition with folate deficiency, a direct toxic influence of alcohol and sequestration in an enlarged spleen. Sideroblastic anaemia caused by interference of alcohol with the metabolism of pyridoxine is common and so is haemolytic anaemia caused by hypersplenism and megaloblastic anaemia. Leucopenia can be seen and is probably caused by a direct toxic effect of alcohol on the bone marrow. Other potentially toxic changes are impaired chemotaxis, motility and adherence of the granulocytes and impaired blast transformation of the lymphocytes. In the bone marrow, vacuolized precursors of myelo- and erythropoiesis are seen. The bone marrow may be hypocellular. Other changes in the bone marrow are increased but ineffective erythropoiesis with defective iron metabolism, vacuolized pro-erythroblasts, multinucleated erythroblasts, megaloblasts and iron-containing plasma cells. PMID- 1509603 TI - [Can progression of myopia be prevented? A literature review]. AB - There is no simple explanation as to when or how myopia commences, nor is there any simple method of preventing the progression of myopia. Non-surgical methods have been attempted: sight training, exercise, drugs to induce cycloplegia and to reduce intraocular pressure, as well as contact lenses and bifocal glasses; none of these have been able to prevent progression. Promising results have been disappointing when these treatments are repeated on larger groups of patients without investigator bias. Surgical procedures for the prevention of progression are not carried out in Denmark at present. New methods of reinforcing the scleral wall also in low grade myopia have been reported from Moscow. Compounds are being injected and transplants are being inserted behind the eye. It is exciting to see whether these results can be reproduced, if trial of this type of treatment is permitted in Denmark. PMID- 1509604 TI - [Pregnant women's knowledge about HIV and AIDS]. AB - This investigation is based upon information from 820 pregnant women who replied to a questionnaire about AIDS during the period 17.4.1989-14.7.1989. The questions included sources of information, knowledge about routes of infection and risk groups and the extent of spread of infection and disease in the population. 95% agreed to participate. Knowledge had been obtained primarily via the electronic media, while the health services had limited significance. The employment of sources of information depended on age and occupation. Apart from knowledge about the risk involved in breast feeding, the women were, in general, well informed about routes of infection. Knowledge about risk groups and the current extent of spread of infection was, on the the other hand, deficient. Defective knowledge was concentrated in groups which may be characterized by age (less than 24 years) and occupation (trained and untrained workers and the group of "other occupations"). Information obtained from health staff was connected with better knowledge about the extent of spread of infection. The majority of women desired routine information about AIDS in connection with antenatal control. Prophylactic measures should be based, among other things, on knowledge about development in the knowledge in the population and its employment of sources of information, so that specific information may be directed to certain groups of the population by using the most frequently employed and most effective routes of information. The knowledge of population groups, the attitudes and behaviour should be followed continuously. PMID- 1509605 TI - [First year experience with a system of mandatory reporting of HIV-positive cases in Denmark]. AB - During the period 1. Aug. 1990 to 31. July 1991, a total of 87,779 HIV-tests were carried out in Denmark on individuals other than blood donors according to the laboratory notification system. Of these 853 were HIV-positive which corresponds to a HIV prevalence of 0.97%. During the same period, 602 persons were notified by doctors as HIV-positive, corresponding to a percentage of notifications of 70. Out of the 602 persons, 84 were repetitions. The sex of two persons was not stated. Further 164 (36%) were previously found to be HIV-positive. Thus there remained 332 (64%) persons who could be classified as positive for the first time. In the material of HIV-positive individuals for the first time, 79% were men and 21% women. The mean age for men was 36 years and 26 years for women (p less than 0.001). 66% of the men were estimated to be infected by homosexual contact, 19% by heterosexual contact and 9% by intravenous drug use. Nineteen of the heterosexually infected men (39%) stated that they had been infected by a woman from a high-endemic region, three by a female drug user and 24 (49%) did not know the source of infection. Thirty of the heterosexually infected women (63%) were considered to be infected by a man from a high-endemic region and 21 of these women were born and had grown up in this region. Six of the women (13%) were considered to have been infected by a bisexual man and eight (17%) by a man without known risk behaviour. HIV-positive persons were notified from all Danish counties, including 57% from Greater Copenhagen. The geographical distribution is not identical for the two sexes. For men, 63% were from Greater Copenhagen and 14% from Jutland while the corresponding distribution for women were 35% and 28% (p = 0.001). PMID- 1509607 TI - [Utilization of cardiovascular drugs in Denmark from 1978 to 1990]. AB - In Denmark, the total sale of medicine increased from 3.1 billion Danish crowns in 1981 to 5.9 billion Danish crowns in 1990. This increase of 91% must be seen in relation to changes in the consumer price index which increased by 77% during the same period. The greatest increase was observed in the sale of antacids and preparations for the treatment of peptic ulceration (189%), drugs for asthma (225%) and antihypertensive drugs (409%). Subdivision of the group of antihypertensive agents reveals an explosive increase in the sale of calcium blockers (in 1990: a total of 158 million Danish crowns) and angiotensin converting-enzyme (ACE)-inhibitors (in 1990: 100 million Danish crowns). Both of these therapeutic principles had been introduced in the nineteen eighties. During the same period, slighter decreases were observed in the consumption of diuretics (194 million Danish crowns in 1990) and beta-blockers (204 million Danish crowns in 1990). This development in the sales figures documents an alteration in the patterns of prescription by practitioners. It must, however, be emphasized that the drugs mentioned here have several different therapeutic indications, some of which were first established during the above mentioned decade. No randomized investigations in the treatment of hypertension are available in which recent therapeutic principles with calcium-blockers and ACE-inhibitors were compared with the previously well tested therapeutic principles involved in diuretics and beta-blockers. PMID- 1509606 TI - [Ultrasonically guided pericardiocentesis]. AB - Ultrasonically guided pericardiocentesis was performed on 25 occasions in 23 consecutive patients. Incipient cardiac tamponade was present in 22 patients and the procedure was performed for diagnostic purposes in one patient. In 21 cases, 5.7 French pig-tail catheters were employed and 1.2 mm lumbar puncture needles in four cases. In 19 out of 22 patients (86%) with incipient cardiac tamponade the ultrasonically guided pericardiocentesis was considered successful. In one patient, the catheter was misplaced in the right atrium, one patient developed pyopericardium and one patient developed transient tachycardia. In two cases, no material could be obtained. Ultrasonically guided pericardiocentesis is preferable to "blind" puncture and the procedure should be carried out by physicians with experience in interventional ultrasound. PMID- 1509608 TI - [Accidents with high-pressure cleansing devices--a new mechanism of injury]. AB - Air and water powered tools are employed increasingly in industry and involve new possibilities for occupational casualties. A new mechanism of trauma is described where the cause of death was an injury to the head, similar to a firearm wound. The "missile" was the water beam from the victim's own high pressure cleansing device, which was able to produce water pressure up to 900 atmospheres resulting in high water velocity of 300 meters/second. As prophylaxis, new legislations, as a result of understandings between employers and employees in the member states of the Common Market, are under preparation at present. PMID- 1509609 TI - [Manipulation with EDTA]. PMID- 1509610 TI - [Adverse effects of water-soluble radiographic contrast media]. PMID- 1509611 TI - Ultrasound in Medicine and Biology Clinical Prize. PMID- 1509613 TI - 1975-2000: a quarter century of ultrasound technology. AB - The most popular forms of ultrasonic diagnostic technology experienced a major transition around 1975 with the introduction of real-time B-mode imaging and the combination of real-time imaging with pulsed Doppler in the Ultrasonic Duplex Scanner. At about the same time, the superposition of Doppler data as color on the gray-scale B-mode image was conceived and demonstrated. Since that time, the instruments have been commercialized and distributed broadly. Except for advancements in scanhead design, the introduction of dynamic focussing on echo receive, and conversion of the instruments from analog to digital processing, little has changed in ultrasound instruments; their size, price, features, and portability have been constant. A fully trained examiner using the most modern instrument made in 1978 can easily adapt the same examination methods to instruments made in 1990. The major change in ultrasound technology has been the increased application of ultrasound examination, specifically Doppler examinations to new organ systems. These trends will change in this final decade of the century. The comments here are from a perspective of noninvasive vascular diagnosis. Each of the advancements in ultrasound technology have resulted from the combined efforts and cooperation of many people. I will not attempt to credit those people here. PMID- 1509612 TI - The early development of neurosonology: III. Pulsatile echoencephalography and Doppler techniques. AB - From the earliest days of echoencephalography, it was noted that echoes from intracerebral interfaces showed systolic pulsations both in amplitude and range. Recordings of larger pulsations in range could also be obtained from the walls of intracranial arteries. It was hoped that clinical information might be obtained from recording and measuring these pulsations. Since it was easier to build equipment that recorded pulsations in amplitude, most work was confined to the recording of amplitude pulsations. However, such recordings of both amplitude and range pulsations usually used range gates in order to isolate the echo of interest and movement of the echoes within the gates introduced artefact in the recordings. Such artefact was more easily identified in recordings of range rather than amplitude. None of these types of recordings resulted in the development of a clinically useful examination in either the living or dying patient. However, the recordings of range fluctuations were able to demonstrate the presence of Traube-Hering waves in the blood vessels of the brain, thus suggesting that these vessels received an autonomic innervation in addition to their chemical sensitivity. Such range recordings also showed that, as a result of the increase in cerebral volume with the arrival of each systolic pulse wave, the brain moved centripetally to compress the cerebral ventricles and downwards to compress the basal cisterns and venous sinuses. The volume increase in the brain was accomodated by displacing cerebrospinal fluid and venous blood outside the rigid skull. When such a venting mechanism was over-taxed, as may result from increased intracranial pressure, it was postulated that the systolic pulse pressure wave, which could no longer be adequately attenuated by the compensatory venting of blood and cerebrospinal fluid outside the rigid skull, gave rise to shock waves which damaged the periventricular ependymal interface and the underlying brain with the production of progressive hydrocephalus. The development of ultrasonic Doppler techniques was quite a different matter and led to a number of clinically useful examinations as the technology became increasingly developed. The Doppler frequency shifts were displayed in various forms culminating in the display of their whole spectrum. Directional displays added further information and the ability to use short pulses enabled the Doppler shift and velocity of blood flowing in small regions of blood vessels to be recorded. Two-dimensional displays of the Doppler frequencies present in blood flowing in vessels were developed concurrently with duplex techniques which made B-mode displays of the blood vessel of interest in a tomogram of the surrounding tissues.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1509614 TI - Computed estimates of maximum temperature elevations in fetal tissues during transabdominal pulsed Doppler examinations. AB - Measured characteristics of ultrasonic fields were obtained in submissions from manufacturers of diagnostic ultrasound equipment for devices operating in pulsed Doppler mode. Simple formulae were used with these data to generate upper limits to fetal temperature elevations, delta Tlim, during a transabdominal pulsed Doppler examination. A total of 236 items were analyzed, each item being a console/transducer/operating-mode/intended-use combination, for which the spatial peak temporal-average intensity, ISPTA, was greater than 500 mW cm-2. The largest calculated delta Tlim values were approximately 1.5, 7.1 and 8.7 degrees C for first-, second- and third-trimester examinations, respectively. The vast majority of items yielded delta Tlim values which were less than 1 degree C in the first trimester. For second- and third-trimester examinations, where heating of fetal bone determines delta Tlim, most delta Tlim values were less than 4 degrees C. The clinical significance of the results is discussed. PMID- 1509615 TI - Cellularity and fibrin mesh properties as a basis for ultrasonic tissue characterization of blood clots and thrombi. AB - This in vitro study was designed to evaluate the ability of ultrasonic tissue characterization (UTC) based on power spectrum analysis of backscattered radio frequency echo signals to distinguish two prominent variables of thrombi: cellularity (primarily red cell content) and fibrin-mesh density. Six types of clots simulating thrombus components were prepared by varying red-cell and platelet concentrations and shear forces during clotting. Data were acquired with a linear-array transducer, digitized, and analyzed in terms of slope and intercept parameters obtained from normalized power spectra of radio-frequency echo signals. Increased cellularity and fibrin-mesh density both produced lower slope and higher intercept values, which permitted statistically significant discrimination of cellularity and mesh density in the six types of clots analyzed. Shearing forces and (to a lesser degree) platelet concentrations increased fibrin-mesh density. This study suggests that UTC based upon the power spectrum of echo signals may be used to detect and follow compositional differences that have clinical relevance in the diagnosis and follow-up of thrombi. PMID- 1509616 TI - Bubble cycling and standing waves in ultrasonic cell lysis. AB - Two quite different but potentially complementary hypothetical mechanisms have been proposed to explain the dependence of ultrasonic cell lysis in vitro on exposure vessel rotation. One mechanism proposes that resonant-size bubbles are trapped in planar arrays by standing waves in the sample and that exposure vessel rotation sweeps cells through the bubble arrays. The other mechanism, for which there is now considerable support, proposes that exposure vessel rotation simply allows bubbles to recycle after having been driven through the medium by the ultrasound. We report here the results of efforts to further discriminate between, and quantify, the relative contributions of these two mechanisms. Murine P388 cells were exposed to 1.07 MHz continuous-wave (CW) ultrasound for 5 min at 5 W/cm2 (ISP) using various exposure vessel compositions and exposure configurations. Experimental treatments were designed either to minimize or maximize standing waves in the sample tube, or to minimize the potential for bubble recycling while maximizing standing wave formation. The results of these experiments indicate that bubble cycling is responsible for the majority of cell lysis occurring in the rotating exposure vessels, but that a significant contribution to total lysis is provided by trapped bubbles under some conditions. PMID- 1509617 TI - Ultrasound Doppler spectral analysis in the diagnosis of occlusive lesions of the carotid arteries. AB - To evaluate the accuracy of Ultrasound Doppler Spectral Analysis (USDA), 432 carotid arteries were examined [group I consisted of 145 cases of normal ICA (internal carotid artery), group II--187 cases of ICA stenosis and group III--100 cases of ICA occlusion]. The maximal systolic peak (Smax), maximal diastolic peak (Dmax), the spectral broadening index (SB) and the pulsativity index (PI) were calculated and related to the degree of stenosis as determined by contrast arteriography. Our results indicate that the change of the value of Smax is the main diagnostic criterion: for carotid arteries' stenoses, it increases to over 3.2 kHz. A Smax over 6.0 kHz is a veritable index of ICA stenosis above 50%: in such cases as the stenosis increases by 10%, this corresponds to an approximately 1 kHz increase of Smax. In ICA occlusion, the main criterion was the absence of blood flow in the distal ICA segment. The UDSA sensitivity in hemodynamically insignificant stenosis is 73.9% which is far higher than in the periorbital Doppler examination; in hemodynamically significant stenosis and ICA occlusions, the sensitivity is 98.6 and 99%, respectively. PMID- 1509618 TI - Duplex scanning of the peripheral arteries: correlation of the peak velocity ratio with angiographic diameter reduction. AB - The correlation of the peak systolic velocity (PSV) and the peak velocity ratio (PVR, calculated as intrastenotic PSV divided by proximally recorded PSV) with percent diameter reduction was studied in 62 patients with peripheral arterial occlusive disease. PSV values correlated well with angiographic diameter reduction (r = 0.81, n = 106 stenoses), but due to large variability the sensitivity and specificity in the detection of greater than 50% stenoses were only 66% and 80% (for a cutoff value of 180 cm/s). The PVR showed less interindividual variability and exhibited a strong correlation with percent diameter reduction (r = 0.93,n = 106 stenoses). A 2.4 fold increase of the peak systolic velocity values with respect to the proximal site (i.e., PVR = 2.4) or more indicated a more than 50% stenosis with a sensitivity of 87% and a specificity of 94%. Figures for PVR are provided to quantitate the degree of stenoses in the 50-99% range. Calculation of PVR may normalize for patient variation and allow noninvasive quantification of lumen narrowing with high sensitivity and specificity. PMID- 1509619 TI - Cerebral blood flow velocity: the influence of myocardial contractility on the velocity waveform of brain supplying arteries. AB - Indices of Doppler-derived velocity waveforms of arteries perfusing the brain are used as relative measures of neonatal brain blood flow. Using a dog model, we investigated the influence of changes in myocardial contractility, induced by dobutamine, on the blood flow velocity waveform of the vertebral artery. The following indices of the velocity waveform were investigated during control states and during 5 or 10 micrograms/kg/min dobutamine infusion: peak systolic flow velocity (PSFV), temporal mean flow velocity (TMFV), end-diastolic flow velocity (EDFV) and acceleration time (ACC-time). PSFV and ACC-time of the vertebral artery showed a strong relationship with myocardial contractile state. These results indicate that PSFV of an artery supplying the brain or indices which combine PSFV with MFV or EDFV should not be used for noninvasive assessment of brain blood flow or cerebral vascular resistance. ACC-time may prove to be very useful in assessing changes in myocardial contractile state. PMID- 1509620 TI - Noninvasive measurement of diameter changes in the distal abdominal aorta in man. AB - An ultrasound phase-locked, echo-tracking system was used to determine the dynamic properties of the distal abdominal aorta in 10 Caucasian male subjects (mean age, 25 years). Recordings were made at rest and during the blood pressure increase resulting from isometric exercise. The pressure diameter curve was nonlinear with an inflection at about 90-110 mmHg. Above this pressure range, the vessel was stiffer (less compliant), but the pressure diameter relationship was roughly linear above as well as below the inflection. Individual pressure diameter curves showed hysteresis, i.e., the aorta had a smaller diameter during expansion than during retraction at corresponding pressures. The pressure strain elastic modulus (Ep) and stiffness (beta) were at rest [Mean Arterial Pressure (MAP), 81 mmHg] 0.70 10(5) N/m2 and 6.0, respectively. During isometric exercise (MAP, 122 mmHg), Ep increased significantly by 91% and stiffness (beta) nonsignificantly by 27%. The variability of the compliance determinations was 5% when the ultrasonic system was combined with intra-arterial blood pressure measurements and less than 7% when combined with auscultatory blood pressure measurements. It is concluded that the phase-locked, echo-tracking system fulfills clinical requirements for routine measurements of vascular compliance. PMID- 1509621 TI - Modest enhancement of ultrasound-induced mutations in V79 cells in vitro. AB - V79 cells were insonated (1 MHz, 35 W/cm2, 2 min continuous wave) under temperature conditions previously reported to cause a large increase in acoustic cavitation. The goal was to increase the ease of detecting ultrasound-induced mutations. The data supported the hypothesis that a 3 degrees C gas-equilibration period followed by insonation at 37 degrees C resulted in a detectable increase in resistance to 6-thioguanine with 6 trials per regimen. PMID- 1509622 TI - High-resolution real-time ultrasonic scanner. AB - High spatial resolution is required for echographic exploration of the skin, microvessels or small laboratory animals. With the scanner described here, high resolution is obtained by means of a strongly focused, wide-band 17 MHz center frequency transducer (-6 dB bandwidth: 22 MHz). The movement of this transducer above the skin provides a 6 mm wide and 5 mm deep echographic cross-section with an image rate of 15 images/s. The resolution is about 0.08 mm in axial and 0.2 to 0.3 mm in lateral directions. The device was tested on phantoms in water and in vivo on normal and pathological skin in the Department of Dermatology. With the easy-to-handle probe, explorations were made on psoriasis, basocellular carcinoma, malignant melanoma and sarcoidosis. PMID- 1509623 TI - A velocity evaluation phantom for colour and pulsed Doppler instruments. AB - We describe a phantom designed to evaluate the velocity measurements made with colour and pulsed Doppler instruments. Using a belt to translate a large volume of semi-rigid material through the entire Doppler sample volume eliminates many of the problems associated with flow and string phantoms. A servo-motor with feedback circuitry ensures accurate control of the belt velocity with an uncertainty in the mean velocity of 0.14%. The phantom provides velocities with typical variations of 0.07 cm/s. We have demonstrated the usefulness of this phantom by evaluating the linearity and accuracy of three pulsed Doppler instruments over belt velocities ranging from 0 to 80 cm/s. In addition, the measurements show the effects of the wall filter at low belt velocities. Using this phantom, we have quantified the accuracy, linearity and precision of the velocity measurements made by three colour Doppler instruments. The results also show regions where the colour instruments are aliased and where the wall filter dominates. PMID- 1509624 TI - Temperature rise in a tissue-mimicking material generated by unfocused and focused ultrasonic transducers. AB - The temperature elevation in a homogeneous tissue-mimicking material with tissue like thermal and acoustic properties, generated by unfocused and focused ultrasonic transducers operating at 1.0 and 3.5 MHz frequencies, was measured. It was found that in the vicinity of a transducer front face, both transducer surface heating and ultrasound absorption are important sources for tissue heating. As for heating due to ultrasound absorption, the experimental results are compared with theoretical predictions for nonperfused tissues resulting from different beam models. The experimental data are in reasonable agreement with the results calculated from a model developed by Nyborg and Steele, a Gaussian beam model and from the model used by the National Council on Radiation Protection and Measurements (NCRP). PMID- 1509625 TI - Quantification of acoustic shock in routine exposure measurement. PMID- 1509626 TI - Protection of bilateral transcranial Doppler transducers during intraoperative monitoring. PMID- 1509627 TI - Genitourinary tract nuclear oncology. AB - Currently available routine radionuclide procedures and on-going investigational scintigraphic studies of genitourinary tract tumors were reviewed. Emphasis was focused on the most commonly encountered tumors located in the kidneys, bladder, and prostate. Other imaging modalities, such as computed tomography (CT), magnetic resonance imaging (MRI), and sonography have replaced many of the routine radionuclide imaging procedures providing high-resolution images and anatomic details. The advantages of radionuclide procedures with their simple, uninvasive, and functioning nature will continue play important role in our management of tumors of the genitourinary tract. PMID- 1509628 TI - Radioisotopic evaluation of renal transplants. AB - Owing to the noninvasive nature, ready availability, and efficacy, radionuclide studies remain widely utilized following renal transplantation for monitoring changes in the functional status and detection of detrimental complications of the grafted kidney. Whereas surgical complications, including vascular occlusion, urine extravasation, drainage obstruction, hematoma, or lymphocele formation, can often be detected effectively, specification of other underlying causes of deterioration of parenchymal function, including acute tubular necrosis (ATN), various types of rejection, and cyclosporine A nephrotoxicity (CyA-NT), frequently cannot be derived independently from the findings of a study without clinical correlation. Besides imaging, plotting of renogram or time/activity curves, numerous quantitative methods have been introduced to provide objective measurements of the blood flow, as well as to gauge the capability of concentration and excretion of the transplanted kidneys. However, the findings whether qualitative or quantitative all have overlapping zones. There is no abnormal image, graphic, or numeric index absolutely specific for any of the possible posttransplant renal parenchymal complications. The differentiation of such conditions may best be achieved through chronologic association of the sequential changes, with or without quantification, detected in serial studies with the clinical presentation and findings. PMID- 1509629 TI - Radionuclide quantitation of renal function. AB - Quantitation of renal function may be performed with a variety of radiopharmaceuticals which reflect slightly different renal functions. Plasma sampling techniques and imaging techniques have been used to derive absolute measurements of renal function. The addition of imaging permits the determination of relative or "split" function. Time-activity curves from renal studies provide other quantitative parameters of function reflecting arterial supply, renal cortical function, and patency of the renal collecting system. Quantitative radionuclide studies of the kidneys provide comprehensive, reproducible, and objective assessments of renal function. PMID- 1509630 TI - Diuretic renography: concepts and controversies. AB - Diuretic renography has proved to be a reliable, noninvasive test for the diagnosis of upper urinary tract obstruction. False positive and false negative results may occur but can be minimized by careful attention to technique. The timing of diuretic administration, state of hydration, and furosemide dosage appear to be the key methodologic variables. PMID- 1509631 TI - Nuclear medicine evaluation of hypertension. AB - Noninvasive diagnosis of renovascular hypertension using nuclear medicine techniques has evolved in the past 30 years through improvements in imaging equipment, radiotracers, and, most recently, captopril intervention. Characteristic patterns of normal and abnormal renograms using typical radiotracers are demonstrated, including renal artery stenosis. Comparison with other tests, both invasive and noninvasive, are made with the aim toward identifying anatomic as well as physiologic definitions of renovascular hypertension. Pitfalls in the methodology are also described. The main advantage of captopril renography is enhancement of the sensitivity, and particularly the specificity, of the radionuclide diagnosis of renovascular hypertension. Available investigations have identified captopril renography as the likely procedure of choice in the noninvasive identification of renovascular hypertension. PMID- 1509632 TI - Radionuclide genital imaging. AB - Despite the emergence of newer cross-sectional imaging approaches, radionuclide techniques have maintained a significant role in genital imaging. While ultrasound is clearly superior for evaluation of scrotal anatomy, radionuclide scrotal imaging remains the most effective method for differentiating between testicular torsion and epididymitis. Labeled red blood cells have been used for varicocele detection in infertile men. Since radionuclide techniques can demonstrate the physiologic status of organs, they play a useful role in evaluating men with impotence (penile scan) and infertile women whose tubal patency is in question (radionuclide hysterosalpingogram). PMID- 1509633 TI - Analysis of kidney volume growth during the fetal period in humans. AB - The growth of fetal kidney volume was studied in 290 specimens taken from 145 fresh human fetuses (85 males and 60 females) with gestational age ranging from 13 to 36 weeks postconception (WPC). Normative equations and curves of the growth of renal volume were obtained for male and female fetuses and for the whole sample in the second trimester (13-24 WPC) and in the third trimester (25-36 WPC) of gestation. There was no difference between the growth in volume of the right and left kidneys. Fetal kidney volume increases with a more intense rhythm in the early fetal period (13-24 WPC). During the second trimester, there was no difference between the values for renal volume of male and female fetuses. In the third trimester, male fetuses had renal volumes significantly greater than the female fetuses. The normative parameters of renal volume could have practical applications in detection and monitoring of renal anomalies in fetal and perinatal urology. PMID- 1509634 TI - Composition of fluids obtained from human epididymal cysts. AB - The fluid composition of five epididymal spermatocoeles, one epididymal cyst and a hydrocoele was examined. The fluid obtained from the spermatocoeles was a dilute suspension of mainly immotile spermatozoa. The sperm-free fluid contained less protein, phosphate, glucose, triglyceride and cholesterol than serum but more testosterone and chloride than peripheral blood. It contained no epididymal secretion products. Proteins in the fluid differed from those in serum. From the fluid composition these cysts appeared to be continuous with the rete testis, either dilatations of efferent ducts or Haller's superior aberrant duct (vas aberrans of the rete testis). Fluid from an epididymal cyst containing no spermatozoa was mainly of similar composition. In contrast, hydrocoele fluid resembles blood serum. PMID- 1509635 TI - Quantitative evaluation of the growth of established cell lines on the surface of collagen, collagen composite and reconstituted basement membrane. AB - As a step in the development of a system for assessing growth of human urothelium and transitional cell carcinoma, the growth of two established cell lines on collagen-based membranes has been evaluated. HT1080 (metastatic human fibrosarcoma) and WI38 VA13 (virus-transformed human fibroblasts) were grown on substrates of collagen, collagen/hyaluronic acid or chondroitin sulphate and reconstituted basement membrane (Matrigel). Cell growth was quantified using a new fluorimetric assay utilizing carboxyfluorescein diacetate. There were differences in morphology between cells grown on collagen and those grown on polystyrene. There were, however, no differences in growth of the WI38 VA13 cells on collagen compared with polystyrene, but growth of the HT1080 cells was increased on membranes of collagen/2.5% hyaluronic acid and collagen/5% chondroitin sulphate, and decreased on Matrigel. Adequate growth on collagen substrates is dependent on cell line. The fluorimetric assay used was suitable for quantifying cell growth on such substrates. PMID- 1509637 TI - Metastatic potential of human renal cell carcinoma: experimental model using subrenal capsule implantation in athymic nude mice. AB - The aim of this study was to determine whether subrenal capsule (SRC) implantation is a suitable model for the study of the metastatic potential of our human renal cell carcinoma (HRCC) lines and to establish new sublines with enhanced metastatic ability. NMRI athymic nude mice 7-11 weeks old received SRC implantation of our HRCC lines RC43 and RC21. These lines were not metastatic when implanted s.c. Mice were killed after 4 or 8 weeks, or when moribund. With the RC43 cell line the success rate for implantation was 69%, with 89% of these showing metastases. The average volume of the implanted tumour fragments was 0.5 mm3 (range 0.28-0.7), the average volume at the primary site at the time of death was 9087 (9-32000) mm3. Metastases were found in lymph nodes, liver, spleen, peritoneum, psoas muscle, pancreas, diaphragm and skin. The average volume of the metastases was 4139 (0.5-9000) mm3. Growing cell lines were established in vivo and in vitro from one splenic, one peritoneal, one diaphragmatic, and one hepatic metastasis. These sublines have faster in vivo and slower in vitro growth rates than the parental lines. With the RC21 cell line the success rate for implantation was 56% and the metastatic rate 78%. The average volume of the implanted tumour was 0.8 mm3 (0.28-1.2), the average volume at the primary site at the time of death was 2685 mm3 (1.4-6534) and the average volume of metastases was 7.1 mm3 (0.5-37.5). Metastases were found in lymph nodes, lung and skin. No establishment was attempted for RC21 because of the small dimensions of these metastases.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1509636 TI - Immunoreactive low-molecular-weight epidermal growth factor in urine of patients with renal cell carcinoma. AB - A specific heterogeneous enzyme-linked immunosorbent assay (ELISA) has been established in order to determine levels of low-molecular-weight epidermal growth factor (EGF) in the urine of patients with renal cell carcinoma who had undergone unilateral radical nephrectomy. Urine specimens, i.e., 20 pre- and postsurgical specimens from a group of patients and 22 from a control group, were assayed after the urine had been freed from high-molecular-weight proteins (greater than 30 kDa) and salts. EGF levels were expressed as urinary EGF/creatinine ratios, and a highly significant decrease (alpha = 0.0005 by Student's t-test) of urinary EGF was found in the patient group prior to surgery. The cancer patients also showed an additional loss of urinary EGF after unilateral nephrectomy (alpha = 0.0005 by Student's t-test). These data correlate with our previous findings that pro-EGF gene expression is decreased in human renal carcinoma and support the concept that low-molecular-weight urinary EGF is derived from high-molecular weight kidney pro-EGF. PMID- 1509638 TI - Elevated levels of serum aldolase A in patients with renal cell carcinoma. AB - To clarify whether serum aldolase A is a useful biomarker for renal cell carcinoma (RCC), we determined serum levels of the aldolase A isozyme by an enzyme immunoassay in patients suffering from RCC, other urological tumors, and benign urological diseases. Forty-six of 126 patients with RCC (37%) had elevated serum aldolase A. The positive rates were 23% in stage I, 40% in stage II, 63% in stage III, and 46% in stage IV. In 10 (83%) of 12 patients whose serum levels had been elevated preoperatively, these were reduced to within the normal range after nephrectomy. Four of 7 patients (57%) with progressive disease had elevated levels of aldolase A. In contrast, the positive rates were only 9.9% in 71 patients with other urological tumors and 5.8% in 52 cases of benign urological diseases. High concentrations of aldolase A isozyme in RCC tissues might be reflected in elevated serum levels. The present findings indicate that serum aldolase A is a useful biomarker for monitoring the clinical course of patients with RCC. PMID- 1509639 TI - Ras oncogene point mutations in bladder cancer resistant to cisplatin. AB - Bladder tumors respond to cisplatin-based chemotherapy in 68% of cases, but only 30% will have a durable response. Recent studies have suggested that ras point mutations may produce cisplatin drug resistance in cell lines. To determine the role of ras point mutations in human tumors resistant to cisplatin, we evaluated ten tumors exposed to cisplatin and eight untreated bladder tumors for ras point mutations. Using polymerase chain reaction DNA amplification and allele-specific oligo-hybridization, we found that only one of the ten treated tumors and none of the untreated tumors harbored a ras point mutation. We conclude that ras point mutations occur infrequently in untreated bladder tumors and do not appear to correlate with cisplatin drug resistance in vivo. PMID- 1509640 TI - [Insurance identification card--privilege of legal health insurance?]. PMID- 1509641 TI - [Emotional-psychiatric disorder and the illness concept]. AB - Who is abnormal--who is sick? Illness is an abnormal state. Abnormal psychological states are manyfold and rich in variations. Therefore it is necessary to define what is insanity and what is personal problem, personal disorder, personal decompensation or only any form of suffering. The problem is important with regard to therapeutical and legal decisions. PMID- 1509642 TI - [Suicide in psychologically healthy patients]. AB - Suicide of mentally healthy persons is of special interest for life insurance. The different positions of suicide research are founded in different definitions of disease in psychiatry and general medicine. The definitions of sickness and mental health are also of importance for emergency medicine and care for the dying. It's fact that most people commit suicide self responsible. PMID- 1509643 TI - [ICD-10 in psychiatric diagnosis. The concept and initial practical experiences]. AB - With introduction of ICD-10 from 1992 in WHO-memberstates there will be considerable change in psychiatric diagnoses. It is the first time that an operational diagnostic approach is introduced in psychiatric routine with a WHO classification system. Following a historical overview basic concepts of ICD-10 and the most important innovations are demonstrated in view of the results of field trials. The new classification was widely accepted during the first tests, reliability of diagnosis could be improved. It should not be overlooked that in spite of methodological perfection many problems regarding content still have to be solved. PMID- 1509644 TI - [Toxic polyneuropathies]. AB - Toxic factors may have damaging effects on the peripheral nerves at different sites: on the axon, on the myelin sheath, on the cell bodies and on the vasa nervorum. The toxic neuropathies can be divided up into polyneuropathies induced by drugs, by industrial, environmental and stimulant poisons. Mostly symmetrical sensory symptoms and signs are the first disturbances, often followed by symmetrical motor pareses. Some polyneuropathies induced by amiodarone, benzene, lead, cimetidine, chloroquine, dapsone, gentamycin, gold, imipramine, hexacarbons, nialamide, penicillin, triorthocresylphosphate and vincristine are primarily dominated by motory losses. Polyneuropathies induced by amitriptyline, ethylene, oxide, lead, chlorprothixene, heroin, hydralazine, methaqualone, nialamide and penicillin show an asymmetrical distribution pattern of the neural losses. In some types of toxic polyneuropathies the cranial nerves and the autonomic nerves are particularly involved. The clinical symptomatology of the most important types of toxic neuropathies are described shortly. The best therapy is, of course, termination of exposure to the toxic substance concerned. PMID- 1509645 TI - [Epidemiologic aspects of multiple sclerosis]. AB - Epidemiology plays a prominent role in the search for environmental risk factors in multiple sclerosis (MS). The basic pattern with the predilection for temperate zones of the globe, whites, females and medium age groups was confirmed throughout. Whether or not MS is increasing in frequency is highly debated. Although no clear risk factors have been demonstrated so far, a certain association of the MS risk with the factors "low temperatures and precipitation", "consumption of animal proteins/fats or meat", "familiar occurrence of MS" and with a late occurrence of common childhood infections became obvious. Many other putative risk factors were not confirmed in most studies. PMID- 1509646 TI - [May an epileptic patient participate in sports?]. AB - Epilepsy is a frequent disease. The question of possible sport activities and epilepsy is important because of the prominent role of sport in the population. The present paper deals with problem if epileptic patients can freely participate in sport or whether they are restricted to a certain extend by their disorder. The aim of this review is to determine the factors which may or may not interfere with sport for the epileptic patient. PMID- 1509647 TI - [Muscular dystrophy as a risk factor in anesthesia]. AB - Three cases of muscular dystrophy are reported on (8 years, 4 months, 10 months) in which serious conditions arose under anaesthetic (bradycardia, asystolia, hyperkalemia, rising CPK). In the first two cases there was no way of avoiding a fatal outcome, but in the third case the child survived with no permanent damage. The cause of incidents of this kind is discussed first as being hyperkalemia due to acute rhabdomyolysis, and secondly malign hyperthermia. There were no indications of malign hyperthermia in this case. It is hardly possible to distinguish this in an acute clinical ward, as the clinical symptoms are very similar. If it is known that muscular dystrophy is present, depolarising relaxants should be given sparingly. This also applies, as the first case shows, for muscular dystrophy of the Becker type, which can on the whole be regarded as benign in comparison with progressive muscular dystrophy of the Duchenne type. In this instance a forensic and anaesthetic expert's opinion even had to be produced at the request of the Public Prosecutor. The post mortem was carried out under the heading of a possible "mistaken medical treatment" but there was no evidence to justify such an assumption. PMID- 1509648 TI - [The geriatric day care clinic--a model also for the management of demented patients?]. AB - The semi-stationary way of clinical treatment (day clinic) is of great importance for the geriatric field. As to diagnostics and therapy of demented patients, day hospital treatment reveal a number of advantages and disadvantages. In particular for fairly serious or seriously ill demented patients daily journey to and from the hospital are too much for them, and their clinical picture deteriorates. On the other hand, the patient benefits from a further integration into the domestic environment alongside with intensive diagnostics and therapy which is not feasible for in-patients. The need of the elderly to keep up their independence in their familiar habitat with all social and emotional contacts can be met better rather by semi-stationary diagnostics and treatment than during a full time stationary care at the hospital. PMID- 1509649 TI - Bovine spongiform encephalopathy: aspects of the clinical picture and analyses of possible changes 1986-1990. AB - A standard questionnaire was used to record the presence of specific clinical signs reported for histopathologically confirmed cases of bovine spongiform encephalopathy observed before June 30, 1990, and the frequencies of these signs were analysed. The signs most frequently recorded were apprehension, hyperaesthesia and ataxia, and there were variations in the frequency with which some signs were recorded in animals observed at different times during the epidemic. These variations were considered to be the result of differences between observers and differences in the duration of the illness, rather than a change in the clinical picture, which could possibly have occurred with a change in the nature of the agent to which the cattle had been exposed, or to a change in their response to the agent. PMID- 1509650 TI - Influence of width and bends on the ease of movement of pigs along races. AB - Pigs could be moved along a race 120 cm wide more quickly than along a race 45 cm wide. The presence of a bend with an angle of 45 degrees slowed their progress by about 10 per cent, a bend of 90 degrees or 120 degrees slowed them by 19 per cent and a 180 degrees bend slowed them by 44 per cent. There was little evidence of any interaction between the effects of width and angle of bend; the effect of a sharp bend could not be compensated for by increased width. The pigs became accustomed to the races and moved more quickly in later runs. PMID- 1509651 TI - Application of in vitro fertilisation techniques to obtain calves from valuable cows after slaughter. AB - The ovaries of two infertile cows of high breeding value were recovered after slaughter, and a total of 222 oocytes were obtained. Of these, 156 were classified as of good or fair quality and were subjected to in vitro maturation, in vitro fertilisation (using frozen semen from three bulls of high breeding value) and in vitro culture procedures. After eight days, 27 embryos were obtained, of which 13 were transferred fresh, and 14 were frozen. Three recipients of fresh embryos became pregnant; two calved and one aborted at four months. One of eight recipients of frozen-thawed embryos became pregnant but aborted at three months. PMID- 1509652 TI - Hyperreactivity to histamine in the jejunum of veal calves with diarrhoea. PMID- 1509653 TI - Multiple anthelmintic resistant nematodes in goats. PMID- 1509654 TI - Drug withdrawal periods. PMID- 1509655 TI - Embryo transfer. PMID- 1509656 TI - Gastrointestinal reaction to piroxicam. PMID- 1509657 TI - BVA policy on animal welfare. PMID- 1509658 TI - Dangerous dogs. PMID- 1509659 TI - Conservative treatment of oesophageal stricture in five foals. AB - Three foals under four weeks old and two under six months old with a history of oesophageal obstruction, had oesophageal strictures of different characters in the rostral cervical oesophagus. One case, which was complicated by severe inhalation pneumonia, was euthanased without any treatment and in another initial treatment by bougienage under general anaesthesia was attempted without success. The four surviving cases were provided with progressively firmer and coarser food, starting with liquid only, over a period of three to four weeks. The treatment is recommended in the early stages of stricture maturation and for strictures which do not involve the deeper layers of the oesophageal wall. PMID- 1509660 TI - A combination of methotrimeprazine, midazolam and guaiphenesin, with and without ketamine, in an anaesthetic procedure for horses. AB - A combination of 0.5 mg/kg of methotrimeprazine, 0.1 mg/kg of midazolam and 100 mg/kg of a 10 per cent guaiphenesin solution was investigated for the induction of recumbency in 15 horses; the addition of 1.6 mg/kg of ketamine was also evaluated in 15 horses and anaesthesia was maintained with halothane in oxygen. The horses became recumbent quickly and smoothly and they recovered quietly, with little ataxia. Tachycardia occurred after induction, but no other changes from pre-operative values were observed until halothane in oxygen had been given, when hypothermia, hypotension, bradypnoea, hyperoxaemia, respiratory acidosis and decreased respiratory minute volume developed. Horses given ketamine in addition to methotrimeprazine, midazolam and guaiphenesin were easier to intubate and recovered more quickly than horses receiving only methotrimeprazine, midazolam and guaiphenesin. PMID- 1509661 TI - Coronavirus serology in healthy pedigree cats. PMID- 1509662 TI - Digital dermatitis. PMID- 1509663 TI - Diagnosis of Echinococcus granulosus infection in dogs. PMID- 1509664 TI - Bizarre effect of a testicular tumour. PMID- 1509666 TI - Siamese calves. PMID- 1509665 TI - Hypovitaminosis C in the guinea pig. PMID- 1509667 TI - Acute toxicological studies on paraquat: pathological findings in beagle dogs following single subcutaneous injections. AB - Sixteen beagles were allocated into 4 groups, each group consisting of 2 males and 2 females, which were injected sc with 1,3,5 or 7 mg paraquat/kg. The beagles were observed for 2 w after the administration. At the end of the observation period all the dying and surviving dogs were studied pathologically. The LD50 was calculated as 1.8 (1.0-6.1) in males and 3.5 (2.4-10.1) mg/kg in females. Clinical laboratory tests showed increases in segmented neutrophils and monocytes, decreases in lymphocytes, slight decreases in chloride, moderate increases in BUN, GOT, GPT and phospholipids, slight increases in uric acid, total protein, creatine, total cholesterol and total bilirubin, and prolonged prothrombin times. Marked edema, congestion and hemorrhage of lungs, as well as slight congestion in various organs, were observed grossly. In histopathological examination, marked pulmonary hemorrhage and congestion, fibroblast-like cells in alveolar septa, breakdown of alveolar walls, thickening of alveolar walls and pleura, mild congestion and degeneration of the liver, and mild degeneration of renal tubules were observed. The cause of death was respiratory distress and renal failure. The surviving animals had mild atelectasis of the lungs. Electromicroscopic examination on the surviving animals revealed the appearance of spindle-shaped cells, proliferation of type II alveolar cells and fibroblasts, mitosis of fibroblasts, and abundant collagen fiber in the lung, calcium deposition, stratification and thickening of basement membranes, and localized necrotic epithelial cells in the proximal tubules of kidneys, and stratification of intramitochondrial cristae of the liver. Pulmonary fibrosis in the switchover stage was present with participation from type II alveolar cells, fibroblasts and myofibroblasts. PMID- 1509668 TI - Toxic effects of low levels of dietary Jatropha curcas seed on Brown Hisex chicks. AB - Jatropha curcas seed, a multi-purpose medicinal plant product, was fed at 0.1 and 0.5% to Brown Hisex chicks for 4 w to measure it's effects upon growth and the structure and function of vital organs. Liver and kidney function tests included serum SDH, GDH, GOT, total protein, potassium and other serum constituents in addition to total tissue lipids and hematology. J. curcas intoxication in chicks was characterized by growth depression, hepatonephropathies and widespread hemorrhages and congestion. PMID- 1509669 TI - The effect of malathion, an organophosphate, on the plasma FSH, 17 beta-estradiol and progesterone concentrations and acetylcholinesterase activity and conception in dairy cattle. AB - The effect of malathion on jugular plasma concentrations of follicle-stimulating hormone (FSH), estradiol (E2), progesterone (P4) and acetylcholinesterase (AchE) on conception in dairy cattle during a cloprostenol (prostaglandin F2 alpha analogue, PG)-induced estrus was studied. Malathion (1 mg/kg, intraruminally) given at the onset of estrus (48 h after PG) did not alter the plasma FSH or E2 concentrations but significantly (P less than 0.05) inhibited plasma P4 concentration. The mean P4 concentration in the malathion-treated group on days 8 and 12 were 0.8 +/- 0.4 and 1.0 +/- 0.5 ng/ml, as compared to 2.6 +/- 0.0 and 2.4 +/- 0.3 ng/ml in the control group. There was a nonsignificant (P greater than 0.05) inhibition of plasma AchE activity in malathion-treated cattle. Conception was 16.6% in malathion-treated cows and 50% in controls. Inhibition of progesterone secretion and poor conception occurred after the single intraruminal dose of malathion at the onset of estrus. PMID- 1509670 TI - Methylene blue can be used to treat methemoglobinemia in cats without inducing Heinz body hemolytic anemia. AB - Methylene blue (MB) is the drug of choice in the treatment of methemoglobinemia (MTHB) in humans and most domesticated animals, but is reported contraindicated in cats. Although prolonged treatment of cats for urologic syndromes with MB containing antiseptics causes Heinz body (HB) hemolytic anemia, there is no evidence to suggest that single or repeated therapeutic doses of MB cause hemolytic anemia. We investigated the efficacy and safety of MB in reversing nitrite-induced MTHB in cats. Forty random-bred adult cats (20 males and 20 females) were divided as follows: Group 1, 1.5 mL saline/kg bw iv (control); Group 2, 1 dose of 1.5 mg MB/kg bw iv; Group 3, 2 doses of 1.5 mg MB/kg bw iv 4 h apart; Group 4 1 dose of 1.5 mg sodium nitrite/kg bw iv; Group 5, 1 dose of 1.5 mg sodium nitrite/kg bw iv followed by 1 dose of 1.5 mg MB/kg bw iv 1 h later; and Group 6, 1.5 mg sodium nitrite/kg bw iv followed in 2 h by 2 doses of 1.5 mg MB/kg iv 4 h apart. One iv dose of MB sufficiently and rapidly reversed MTHB in the cats without increasing circulating HB-containing red blood cells. Giving 2 iv doses of MB without or after sodium nitrite significantly increased the frequency of circulating HB-containing red blood cells. Pre-exposure to sodium nitrite potentiated the HB-inducing effect of 2 doses of MB. Hemolytic anemia was not observed or demonstrated in any of the cats groups. PMID- 1509672 TI - Fetotoxic response of technical quinalphos in rats. AB - Technical Quinalphos was administered po to pregnant rats through day 6-20 of gestation at doses of 0.5 or 1.5 mg/kg body weight. Quinalphos produced enzymatic changes in liver and serum of dams associated with mild pathomorphological changes in liver and brain. Fetotoxic effects were not observed at the tested dose levels as determined by total number of implantations, percentage resorption, live fetuses, crown rump length and fetal weight. A few insignificant skeletal deformities were noticed. A significant inhibition of acetylcholinesterase activity in fetal brain and placenta indicated possible transmigration of quinalphos from dams to fetuses. PMID- 1509671 TI - Inhibition of intestinal glucose absorption in rats treated with 2,3,7,8 tetrachlorodibenzo-p-dioxin. AB - Male Sprague-Dawley rats were injected with either 125 micrograms 2,3,7,8 tetrachlorodibenzo-p-dioxin (TCDD)/kg or vehicle (pair-fed and ad libitum-fed controls). Transfer of water, electrolytes and D-glucose as well as fats of a tracer dose of the non-metabolizable radioactive marker 3-O-methyl-D-[U 14C]glucose was studied in isolated perfused jejunal segments 1, 2, 7, and 21 d after treatment (TCDD-treated and pair-fed control rats) and after 26 d in ad libitum-fed controls. TCDD-treated rats demonstrated reduced feed consumption and loss of body weight. Active intestinal absorption of glucose was significantly inhibited 30 and 22% compared to pair-fed controls, respectively 2 and 7 d after TCDD treatment. After 21 d the inhibition (14%) was less significant. There were no differences in glucose transfer between severely starved pair-fed controls (body weights 370 +/- 26 g) and ad libitum-fed rats (body weights 512 +/- 15 g). Water absorption and transfer of sodium and calcium was not influenced by TCDD treatment. However, a significant increase of potassium transfer was observed in parallel with impaired glucose absorption. The uptake of 3-O-methylglucose into mucosal tissue was not impaired, whereas the transfer to the serosal side was significantly inhibited by 30-60% compared to pair-fed as well as ad libitum-fed animals from day 2 until the end of the experiment. These results suggest that TCDD is involved in an inhibition of glucose transport at the basolateral membrane. PMID- 1509673 TI - Role of socialization, stress and sex of chickens on response to anesthesia and on response to an organophosphate neurotoxicant. AB - The influence of socialization of chickens on response to exogenous substances in the presence and absence of stress was examined. Chickens of both sexes were habituated to human beings (socialized) by being talked to and offered food from the hand of the caretaker. After 19 w, half the socialized group and half the unsocialized group were subjected to stress (loud noises for 120 sec twice daily) for 2 w. At the end of this period, response to 37 mg pentobarbital/kg iv was evaluated by length of sleeping time. Males slept longer than females, and males that were socialized but not stressed slept significantly longer than other males. Stress and socialization did not significantly affect pentobarbital sleeping time in females. This indicated that response to pentobarbital was dependent on sex and on socialization, with the most notable effects occurring in socialized males. Socialized and nonsocialized, stressed and unstressed male and female chickens were also administered a single po dose of 360 mg tri-ortho-tolyl phosphate (TOTP)/kg. This organophosphorus ester induced a delayed neuropathy that caused ataxia in all the chickens. The ataxia was significantly more pronounced earlier in males than in females, although the sex difference became insignificant 18 d after dosing. Socialized chickens were ultimately more affected. Noise stress did not affect TOTP-induced ataxia. This indicated that response to an organophosphate neurotoxicant was also dependent on sex and socialization, with the most notable effects again seen in socialized males. Response to endogenous substances in chickens depends both on sex and on familiarity to humans. PMID- 1509674 TI - Effect of phenobarbitone pretreatment on the toxicity of temik and sumicidin in Nubian goats. AB - Pretreatment of Nubian goats with 14 daily doses of 20 mg phenobarbitone sodium/kg increased the toxicity of temik (aldicarb) and sumicidin (fenvalerate) as reflected by the development of more severe clinical signs and lesions and in death in the pre-treated goats. PMID- 1509675 TI - Subchronic oral administration of acemannan in the rat and dog. AB - Acemannan is the USAN-accepted name for long-chain polydispersed beta-(1,4) acetylated polymannose with interspersed O-acetyl groups, with a mannose monomer/acetyl ratio of approximately 1:1. This complex polysaccharide is extracted from Aloe vera (barbadensis Miller); the technical material contains approximately 78% acemannan. Technical grade acemannan was administered po to rats for 14 d at 5% of the diet and for 6 mo at up to 2,000 mg/kg/d, and to beagle dogs for 90 d at up to 1,500 mg/kg/d without significant effect on any parameter measured in either species. PMID- 1509676 TI - A regional poison center's experience with poisoning exposures occurring in schools. AB - The nature of and response to poisonings in the school setting has not been characterized. To define these problems a retrospective review of calls to a Regional Poison Information Center (RPIC) involving school exposures was done for the 1988-89 academic year. 362 cases were reported; 74% were reported by school nurses, 10% by other school employees, 10% by parents, 5% by health care facilities, and 1% by students themselves. Ingestions accounted for 45% of exposures, dermal 24%, ocular 19%, inhalation 7%, with the remainder being combinations of routes. Correct treatment prior to RPIC consultation occurred in only 40% of the cases. None developed major symptoms, 23% had minor and 10% had moderate symptoms. High school students accounted for the greatest number (20) of suicide gestures, while middle schools reported more cases of substance abuse. School nurses often were unaware of situations until several hours later. 61% of suicide gestures were referred to an HCF; 7 of these developed moderate symptoms. Exposures to chemicals in science or vo-tech classes accounted for 102 cases; 28% were referred to a HCF and 15% had moderate symptoms. There was often a delay in evaluation by the school nurse and initial decontamination was inadequate or absent. Parents were often instructed by school personnel to contact the RPIC for information and then relay it to the school. These delays could have resulted in greater toxicity. School nurses should be targeted for educational programs by poison centers, but teachers and other school employees must also be included since often they are the first at the scene. Students should be instructed to report exposures to a teacher immediately. PMID- 1509677 TI - Factors influencing non-compliance with poison center recommendations. AB - Non-compliance with prescribed therapies has long been recognized by medical practitioners in all fields as an important factor influencing the probability of a favorable outcome. Few references in the literature address this factor with regard to poisoning. Principles of assessing and improving compliance may also be applied to the advice given by poison information providers. Cases involving lay callers, who failed to comply with poison center recommendations, were studied. The type of advice, reason given for failing to comply, and outcome were assessed. 205 poisoning cases from the 12-mo period were analyzed involving 129 children and 76 adults. In 34 pediatric exposures of children where syrup of ipecac was recommended but not given, 29.4% of parents cited the influence of a family member in deciding not to comply; 47% indicated the potential risk of the exposure was not perceived accurately. In 90 cases of non-compliant referrals of children to emergency departments, 60% of parents minimized the threat of a serious outcome despite explanation of the expected risk. In 76 adult cases, 70 patients refused referral to an emergency department; 26% admitted to sociopsycological reasons, including public status, undisclosed drug abuse, or fear of reprisal. Sequelae developed in 31% of the children and 46% of the adults which may not have occurred if poison center recommendations had been followed. Willingness to comply with a recommended behavior is influenced by factors such as motivation, concern, perceived threat posed by the exposure, and perceived barriers. A compliance model relative to poisoning is needed to reduce risk and promote a favorable outcome. PMID- 1509678 TI - Hepatotoxic constituents in the rumen of Brachiaria decumbens intoxicated sheep. AB - Spectroscopic examinations of purified extracts of the rumen content of sheep intoxicated by Brachiaria decumbens revealed the presence of a mixture of sapogenins, identified as 3-spirostanols. These isomeric steroid sapogenins (C27H44O3) are believed the toxic principles in causing toxicity in sheep after feeding on B. decumbens. PMID- 1509679 TI - Malathion-induced epidemic hysteria in an elementary school. AB - More than 100 people, including firefighters, police officers, paramedics, nurses and physicians responded to reports that students at an elementary school had been exposed to an unknown and possibly toxic substance; 296 students were transported to eight hospital emergency departments. None were diagnosed as acutely ill. The substance was subsequently identified as approximately 22 ml of malathion, diluted in 15 L of water and applied by means of a hand-held sprayer approximately 100 m from the school. The odor apparently drifted to the school in 19 to 24 km/h winds. The episode was determined to be epidemic hysteria, possibly triggered by the malathion odor, but perpetuated by the stress of the emergency response. Hallmarks of epidemic hysteria are discussed, and recommendations for dealing with similar events are offered. PMID- 1509680 TI - Oak (Quercus incana) leaf poisoning in cattle. AB - Oak poisoning occurred in crossbred cattle due to eating immature tender oak (Quercus incana) leaves. Mortality was 70%. The animals exhibited anorexia, severe constipation and brisket edema. The feces were hard, pelleted and coated with blood and mucous. Significant reductions in blood hemoglobin and mean corpuscular hemoglobin, and significant elevations in serum bilirubin were observed. Serum urea nitrogen and creatinine were greatly increased. There was bilirubinuria, proteinuria, hypoproteinemia and hypocalcemia, and greatly increased activities of serum aspartate aminotransferase, lactate dehydrogenase and alkaline phosphatase. The levels of tannins and condensed tannins were 97.7 mg tannic acid equivalent and 5.8 mg catechin equivalent/g of dry leaves. There was extensive nephro- and hepatotoxicity in the affected cattle due to hydrolysable tannins and simple phenols in the oak leaves. PMID- 1509681 TI - Paraquat poisoning in children: survival of three cases. AB - Five children with paraquat poisoning are presented. Three were diagnosed early, treated and survived; the other 2 arrived 1-2 days after paraquat ingestion and died subsequently from respiratory failure due to pulmonary fibrosis. PMID- 1509682 TI - Toxicology consultation fees to health care facilities: a successful revenue generating program for poison centers. AB - Poison information center funding is a continuous problem and is growing more critical as cost containment effects the health care industry. Although a limited number of poison centers are partially funded by governmental agencies, general poison center operational support is derived from a variety of sources, and there is significant pressure upon centers to identify alternative funding sources. Affiliated members of our member hospital treatment network have provided one revenue source, but not all hospitals within our service region have subscribed. Furthermore, hospitals outside of our service region have utilized the service without any financial responsibility despite recommendations to use their local center. Therefore, to provide an incentive for local hospitals to subscribe to the service and to dissuade hospitals from outside of the region from using the service, we implemented a toxicology consultative fee for service on all calls emanating from non-member hospitals. In just 19 mo, recruitment of 16 new member hospitals has generated $65,150 additional revenue. Non-member hospitals electing not to affiliate but to remunerate for toxicology consultations (226 cases) have generated $20,400 (98% collection rate). A startling 95% reduction in calls from hospital outside of region has resulted since this fiduciary initiative began. New revenue totaling $85,550 has been generated by establishment of a toxicology consultation fee, and our staff is now able to dedicate priceless time and resources to the poison information needs of the residents of our region. PMID- 1509684 TI - Imprint coding on solid medication forms: problems in interpretation. AB - Currently, the FDA is planning to mandate imprinting on all solid medication forms. Regardless of the system it employs, identifying the manufacturer accurately and quickly is critical. Our data demonstrate that the current use of "logotypes" falls far short of minimally acceptable accuracy. We urge use of clear identifiers and that the proposed system be tested in the field prior to its implementation. PMID- 1509683 TI - The poison center as a reservoir for antidotes for veterinary poisoning emergencies. AB - Animal poisonings account for a significant number of the cases responded to by poison centers. The majority of consultations involve small animals and do not necessitate the use of large amounts of pharmacologic antagonists, such as atropine to treat anticholinesterase pesticide poisonings. However, large animals such as cattle present unique management problems, since phenomenal amounts of antidotes may be needed to treat a herd of cattle, creating a significant economic impact. The most challenging dilemma is providing 24-h availability and a means of acquisition of sufficient quantities of antidotes to reduce the economic impact of large-animal poisonings. In conjunction with a state veterinary medical association, a RPIC serves as a depot for the storage and distribution of emergency veterinary antidotes. Sufficient quantities of atropine, methylene blue, calcium EDTA, sodium nitrite and thiosulfate, and activated charcoal are available via the RPIC to treat a herd of 200 cattle. The antidotes are available only for emergency treatment and with a veterinary prescription. The 24-h nature of the poison center makes it an ideal location to serve the needs of veterinarians. PMID- 1509685 TI - Commentary ... "lead non-poisoning". PMID- 1509686 TI - In vivo evaluation of the adsorptive capacity of activated charcoal for camphor. AB - Camphor, a cyclic terpene, is the toxic ingredient in many over-the-counter (OTC) products. Early seizure activity due to camphor ingestion often contraindicates the use of traditional decontamination therapies in favor of oral activated charcoal use. No research data supports the affinity of activated charcoal for camphor. This study was conducted to evaluate the effectiveness of activated charcoal in preventing camphor absorption in a rat model. Camphor 40% in cottonseed oil (1 g/kg) was administered to 100 male Sprague-Dawley rats via oral gavage. Aqueous activated charcoal suspension (2 g/kg) was administered to the study group of 50 rats. Serum camphor concentrations were determined by gas chromatography at defined intervals over 10 h. No mortality occurred in either the control or activated charcoal-treated group. Area-under-the-curve bioavailability comparisons of each group revealed no significant differences (activated charcoal 421 micrograms x h/ml vs camphor 409 micrograms x h/ml). The absorption rate constants (Ka) and T 1/2 and elimination rate constants (Ke) and T 1/2 of each group were nearly identical and similar to those reported for humans. These preliminary data indicate the need for careful evaluation of the efficacy of oral activated charcoal administration as the sole means of preventing the absorption of camphor. PMID- 1509687 TI - The administration of desferrioxamine to paraquat-intoxicated rats. AB - We investigated the effect of desferrioxamine, an effective iron chelator, on animal survival and on plasma vitamin E levels after administration of paraquat doses close to the LD50. Male Sprague-Dawley rats received 20 mg paraquat/kg followed by 300 mg desferrioxamine/kg/d given ip over 2 d at 3 equal intervals. The results suggested that desferrioxamine prevented the paraquat-induced depletion of vitamin E, but did not improve the mortality due to paraquat. In ancillary in vitro experiments with a paraquat-based free radical system, where glutathione reductase and NADPH were used as sources of enzymic activity for the redox cycling of paraquat, desferrioxamine effectively prevented the formation of hydroxyl radicals, as determined by deoxyribose degradation. PMID- 1509688 TI - Response of brown hisex chicks to low levels of Jatropha curcas, Ricinus communis or their mixture. AB - Feeding Jatropha curcas seed at 0.5% of the basic diet for 2 w was not lethal to chicks. In chicks fed 0.5% Ricinus communis seed or a mixture of 0.5% J curcas + 0.5% R communis for 2 w, there was dullness, poor growth, locomotor disturbance and death. Pathological changes were correlated with alterations in clinical chemistry and hematology. PMID- 1509689 TI - Effects of bracken fern (Pteridium aquilinum L Kuhn) feeding during the development of female rats and their offspring. AB - Bracken fern (Pteridium aquilinum L Kuhn), is widely food in many parts of the world; the toxic effects have been demonstrated on many species of animals, and both carcinogenicity and enzootic hematuria has been studied. We investigated the effects of feeding bracken fern on the development of female rats and their offspring. The plant was fed as 30% of the normal diet on an ad libitum basis. Bracken fern did not modify the weight gain of the female rats during development, nor affect estrus cycle duration or milk production, the plant did reduce female fertility and weight gain during pregnancy. It also adversely affected physical and neurobehavioral development in the offspring. PMID- 1509691 TI - 1992 AAPCC/AACT/ABMT/CAPCC annual scientific meeting. Tampa, Florida, September 18-22. Abstracts. PMID- 1509690 TI - Toxicological interactions of Abrus precatorius and Cassia senna in the diet of Lohmann broiler chicks. AB - The combination of 0.5% Abrus precatorius seed and 2% Cassia senna fruit in the diet of Lohmann broiler chicks caused severe lesions, reduced weight gain, inefficient feed utilization and anemia. Organ lesions correlated with changes in clinical chemistry and hematology. Tissue recovery was not complete 2 w following withdrawal of the test diet. Feeding 0.5% Abrus or 2% Senna diets alone produced decreased growth and tissue lesions that did not return to normal 2 w following return to normal rations. PMID- 1509692 TI - Abnormalities of smooth pursuit and saccadic control in schizophrenia and affective disorders. AB - Smooth pursuit abnormalities have been reported in patients with schizophrenia and their first-degree relatives, suggesting that abnormal tracking may serve as a biological marker for schizophrenia. Recent studies in schizophrenic patients have found reduced pursuit gain, low initial acceleration and abnormal gain corrective saccade interactions. Impaired saccadic initiation has been noted in anti-saccade tasks and in predictive saccade generation, as has saccadic hypometria. While abnormalities have been found in affective disorder patients, studies of their first-degree relatives suggest that abnormalities during pursuit are more closely associated with schizophrenia. Identification of specific defects allows informed speculation about their neural substrates and suggests possible relationships between the ocular motor defects and other cognitive and perceptual abnormalities associated with the major psychiatric disorders. PMID- 1509693 TI - The perception of globally coherent motion. AB - How do human observers perceive a coherent pattern of motion from a disparate set of local motion measures? Our research has examined how ambiguous motion signals along straight contours are spatially integrated to obtain a globally coherent perception of motion. Observers viewed displays containing a large number of apertures, with each aperture containing one or more contours whose orientations and velocities could be independently specified. The total pattern of the contour trajectories across the individual apertures was manipulated to produce globally coherent motions, such as rotations, expansions, or translations. For displays containing only straight contours extending to the circumferences of the apertures, observers' reports of global motion direction were biased whenever the sampling of contour orientations was asymmetric relative to the direction of motion. Performance was improved by the presence of identifiable features, such as line ends or crossings, whose trajectories could be tracked over time. The reports of our observers were consistent with a pooling process involving a vector average of measures of the component of velocity normal to contour orientation, rather than with the predictions of the intersection-of-constraints analysis in velocity space. PMID- 1509694 TI - Visual memory for vernier offsets. AB - Human ability to perceive and remember precise spatial relationships was investigated in a vernier acuity task. An initial ("standard") vernier stimulus with a variable offset was presented for 100 msec. After a delay of 1, 4, or 8 sec, another vernier target (the "variable" stimulus) followed, also for 100 msec. Observers compared the offsets of the two stimuli with each other. For very small offsets, discrimination between smaller and larger offsets was very precise, in the hyperacuity range. Thresholds increased linearly with the spatial offset of the standard stimulus, suggesting that the precision of the mechanism solving this spatial task scales with offset size. Control experiments suggested that this effect was not due to variations in retinal eccentricity. Thresholds also increased with increasing delay between the presentations of the two stimuli. By varying the delay, we directly measured the fading of the spatial memory trace. PMID- 1509695 TI - The effects of common movement and spatial separation on position- and motion based judgements of relative movement. AB - When common movement is superimposed on relative movement (changes in separation between two dots), relative movement thresholds increase nonlinearly as a function of initial dot separation. For large separation (greater than 2.0 deg), thresholds increase gradually with increased separation. It is shown that this reflects judgments based on perceived relative motion. For small separations (less than 2.0 deg), thresholds increase sharply with increased separation. It is shown that this reflects judgments based on perceived changes in relative position. Evidence is presented that superimposed common movement reduces sensitivity to relative movement by reducing sensitivity to relative motion. This provides a "window", in the range of small dot separations, for relative movement judgements to be based on the perception of changes in relative position, even though motion is perceived for individual dots. PMID- 1509696 TI - Sustained and transient properties of chromatic and luminance systems. AB - Reaction times were measured to 450 and 650 mm test increments to examine the temporal behavior of the chromatic and luminance systems. A response-terminated random foreperiod paradigm was employed. Stimuli consisted of chromatic test increments upon backgrounds of varying spatial structure. Conditions were chosen which may preferentially favor the reaction time response being mediated by the chromatic or luminance systems. The temporal properties of the chromatic and luminance systems were demonstrated by the shape of the estimated hazard functions of the reaction time distributions. When the white background was spatially coincident with the test field, the hazard functions showed a relatively small peak. As white sectors were added to the annulus surround (introducing spatial transients between test and background fields), however, the hazard functions became more and more peaked. The hazard functions of the luminance system were estimated by assuming that the chromatic and luminance systems function in parallel. We concluded from the results that the chromatic system may be characterized as a quasi-sustained mechanism and the luminance system as a transient mechanism. PMID- 1509697 TI - Visual suppression of torsional vestibular nystagmus in rhesus monkeys. AB - Juvenile rhesus monkeys, placed on a motorized turntable, were rotated at constant velocity and then decelerated about an Earth-vertical axis. The animals were implanted with dual search coils to measure eye movements in three dimensions. By changing the monkey's body position (upright, ear-down, supine), postrotatory nystagmus was elicited in the horizontal, vertical, or torsional direction. Peak slow phase eye velocity and time constant of velocity decay were compared between decelerations in the dark and in the light. In all nystagmus directions, illumination reduced the time constant (Tc) to values around 5 sec. Peak velocity (Vp) was markedly attenuated in the horizontal and vertical directions (around 50%), but the effect of light on Vp in the torsional direction was small (less than 20%). These findings were independent of the velocity step size. Our hypothesis is that the two dynamic components of optokinetic nystagmus, as they interact with postrotatory nystagmus during visual suppression, differ in their dimensionality: the early component (fast component, direct pathway, pursuit system) is mainly activated in the horizontal and vertical directions, while the late component (slow component, indirect pathway, optokinetic system) effectively operates in all three dimensions. PMID- 1509698 TI - Is the visual field temporally homogeneous? AB - We asked the question "is the visual field temporally homogeneous when the well known spatial inhomogeneity is taken into account?" Our results show that the visual field exhibits inhomogeneity for stimuli of low spatial frequency for which the spatial inhomogeneity is minimal. This inhomogeneity takes the form of a reduction in sensitivity for stimuli of low temporal frequency in the periphery and an enhancement of sensitivity for stimuli of high temporal frequency in the periphery. The low temporal frequency loss in the periphery is post-receptoral and must involve a selective loss of sensitivity of the low pass filter. The enhanced high frequency sensitivity may be post-receptoral or purely receptoral. The consequence of such an inhomogeneity for subsequent stages of visual processing is discussed. PMID- 1509699 TI - The coding of spatial position by the human visual system: effects of spatial scale and contrast. AB - In this study we investigate the nature of the computations that underlie the encoding of spatial position by the human visual system. Specifically, we explore the relationship between alignment accuracy and spatial scale on the one hand, and between alignment accuracy and contrast on the other. We do this for stimuli where local luminance, local contrast, and orientation cues do not underlie performance. The results suggest that spatial localisation is independent of spatial scale and weakly dependent on contrast. We present subsequent models based on the properties of some classes of visual cortical neurones, namely multiplicative noise and contrast energy detection of complex cells, which describe the form of these relationships. PMID- 1509700 TI - Extraocular muscle forces in alert monkey. AB - We describe an extraocular muscle (EOM) force transducer that provides low-noise signals from an alert animal for several months, is implanted without disinserting the muscle, and is well-tolerated by the body, and present results obtained with the device. The transducer can be used to study orbital statics and dynamics, and oculomotor control signals undiminished by orbital low-pass filtering and antagonistic pairing of muscles. It may provide an index of effective EOM innervation, useful in studies of orbital tissue healing and plasticity, and oculomotor (OM) signal adaptation. During horizontal saccades transducers implanted in the lateral rectus (LR) and medial rectus (MR) of a monkey trained to fixate revealed an agonist muscle tension waveform corresponding to the "pulse-slide-step" pattern of saccadic innervation, and an antagonist waveform that was similar within a scale factor. We never observed transient increases in antagonist force at the ends of saccades (active braking) or at the beginnings. Onset of saccadic force in LR preceded that in MR by 1.6 msec for abducting saccades, and lagged that in MR by 1.1 msec for adducting saccades. During vertical saccades, transient force changes were found in LR and MR, which were likely due, at least in part, to globe translation. LR and MR forces during fixation tended to be largest with the eye about 10 degrees in elevation, and smallest in depression, indicating that effective total innervation was a function of vertical gaze, or that there was variation in the elastic component of muscle force related to orbital geometry, with LR and MR innervation independent of vertical gaze. An exponential decrease in fixation force, having a time constant of about 10 days, was observed after implantation. This may have reflected adaptive muscle lengthening or post-surgical healing. PMID- 1509701 TI - Visual remapping in infantile nystagmus. AB - The possibility that patients with idiopathic infantile nystagmus achieve spatial constancy by visual remapping was investigated by comparing subjective localization of flashed test targets to their absolute position in space and to their absolute position on the retina. Nystagmats first viewed a screen stationary reference target that was followed by a test flash. A computer used eye movement feedback to precisely control the test flash position on the retina. All six nystagmats detected test flashes throughout their nystagmus cycle. For three nystagmats test flashes (total N = 48) were delivered to the same retinal locus that were, at different times, to the right and left of the reference target. More than two-thirds of such crossover stimuli were correctly located in space: when only those stimuli at least 0.5 deg from the reference were considered, two of three subjects correctly located all stimuli. Taken together these results argue that our subjects could see throughout the nystagmus cycle and shifted their visual map in synchrony with their nystagmus as an explicit means of avoiding oscillopsia. PMID- 1509702 TI - Visual segmentation of a heterochromatic field into center/surround components. AB - The process of visual segmentation was studied by quantitatively estimating the apparent difference (i.e. the perceptual contrast) between two segments of a heterochromatic field. A chromatic test bar (Munsell 5R 6/6, 5BG 6/6, 5Y 6/6, or 5PB 6/6) was centered in an achromatic surround (Munsell N6) and the luminance contrast between the test bar and surround was varied between 0 and 39%. At equiluminance (0% luminance contrast) the chromatic border between center and surround was vague and perceptual contrast was minimal. When luminance contrast was increased slightly (5-15%) the border between center and surround was more distinct and perceptual contrast was almost two times greater than predicted by a model that combines spatial differences in chromaticity and luminance as orthogonal vectors. A luminance border may enhance perceptual contrast by increasing the salience of the center/surround hue difference. A vector model is consistent with perceptual contrast only at relatively high luminance contrasts, where hue differences play a relatively minor role in visual segmentation. PMID- 1509703 TI - The effects of colour adaptation and stimulus size on white perception as a function of eccentricity in man. AB - We studied how much desaturating complementary colour had to be added to blue, green or red after homochromatic adaptation of short duration in order to perceive white or grey at eccentricities of 0-15 deg in the nasal visual field. The CIE 1931 (x,y) chromaticity coordinates corresponding to achromatic perception were subtracted from the chromaticity coordinates of blue, green and red in order to obtain the threshold differences (dx, dy) in chromaticity coordinates. When the stimulus size was constant at all visual field locations, the absolute values of dx and dy decreased with increasing eccentricity, which means that the desaturation threshold for white or grey perception was higher at the fovea than in the periphery. However, when the stimulus size was M-scaled magnifying its size with increasing eccentricity in inverse proportion to the lowest local sampling density of the human retina (cones and ganglion cells at eccentricities 0-10 and above 10 deg, respectively), dx and dy with blue became independent of visual field location except for the very centre of the fovea. However, M-scaling was unsuccessful with green and red. Although M-scaling with green reduced the change in dx and dy as a function of eccentricity, it had no effect on dx and dy with red colour. PMID- 1509704 TI - Lateral motion bias associated with reading direction. AB - We found that when Americans view ambiguous lateral long-range apparent motion, they exhibit a robust bias to experience leftward movement. In successive experiments, right-handers and left-handers, and left-side drivers from Japan equally manifested this leftward bias. However, bilingual viewers whose first language reads from right to left exhibited no lateral bias. Furthermore, the bilingual sample produced a significant correlation between exposure to English and extent of leftward motion bias. The findings provide strong evidence that reading habits can influence directionality in motion perception. PMID- 1509705 TI - Spatial frequency tuning of facilitation by masks. AB - The spatial frequency tuning of facilitation by masks is derived for a 2 c/deg test grating, counterphased at 8.8 Hz, from the contrasts at which masks of different spatial frequencies facilitate maximally. This tuning function has a bandwidth at half height of roughly 1.5 octaves, much broader than has been estimated previously from tuning functions determined at a constant contrast for each mask. We show also that best facilitation more than doubles sensitivity for tests of 4 c/deg and below, and that the magnitude of the facilitation effect declines at higher spatial frequencies. PMID- 1509706 TI - Barn owls have symmetrical accommodation in both eyes, but independent pupillary responses to light. AB - We have studied accommodation behaviour in the barn owl (Tyto alba). By defocussing one eye with various spectacle lenses and recording the refractive state in both eyes continuously during pecking, we found that the owls' accommodation was symmetrical in both eyes, with no regard to the power of the lens used. Even with no visual input to one eye, the amount of accommodation was always identical in both eyes. On the other hand, pupillary responses to light were independent. This finding differs from an earlier observation in the chicken, where both accommodation and pupillary responses were found to be independent. The result is discussed with regard to current knowledge on the central pathways for control of accommodation and pupillary responses in birds. PMID- 1509707 TI - Infant temporal contrast sensitivity at low temporal frequencies. AB - The data on infant temporal contrast sensitivity functions (TCSFs) are scarce and contradictory. Earlier studies suggest that critical flicker frequency (CFF) is adultlike at 2-3 months postnatal (Regal, D. M., 1981 Vision Research, 21, 549 555), while contrast sensitivity at low temporal frequencies remains poor. If both of these findings are true, then infant TCSFs are much flatter than those of adults. In the present study, we have re-investigated 2-month-olds' contrast thresholds at low temporal frequencies. To match the conditions of Regal's CFF study, test fields were embedded in a luminance-matched surround. As in previous studies, low contrast sensitivities were found. Models of infants' flat TCSFs are discussed. PMID- 1509708 TI - Temporal contrast sensitivity in human infants. AB - Temporal contrast sensitivity was measured in 1.5- and 3-month-old infants using the FPL procedure. Stimuli were 0.1 c/deg counterphase-flickering sinewave gratings. Temporal rates ranged from 1 to 20 Hz. Because the spatial sinewave underwent phase shifts of 180 degrees, the target could not be seen unless the observer was able to resolve it temporally. Adults were tested with the same temporal stimuli using a 2-alternative forced-choice procedure and a spatial frequency of 0.5 c/deg. Adult temporal CSFs were bandpass with peak sensitivity at 10 Hz. Infant temporal CSFs were lowpass at 1.5 months and bandpass at 3 months. The infants' contrast sensitivity was over a log-unit lower than adults'. Unlike spatial CSFs, infant sensitivity was closest to adult sensitivity at the highest flicker rate. PMID- 1509709 TI - Control of interocular suppression as a function of differential image blur. AB - This experiment studied normal adults, normal children, and corrected strabismics with alternating fixation, evaluating their ability to detect information presented to one eye under viewing conditions which might affect their eye preference. An apparatus was used which allowed unconstrained, binocular viewing of a video monitor, but in which the image seen by one eye was blurred while that seen by the other eye was in sharp focus. Under these viewing conditions, subjects were asked to identify a sharply focused letter which was shown briefly to the eye which was seeing the blurred background image or to the one which was watching the well-focused image. The question was whether there would be general suppression of the eye that was shown a degraded background, causing a reduction in its ability to process other information being presented. The results indicate no performance penalty for children, a mild decrement in recognition accuracy for normal adults, and a severe deficit in the ability of corrected strabismics to attend to the eye which views a blurred image. These results suggest that the loss of binocular vision that accompanies childhood strabismus is not a result of an inherent sensitivity to blurring, insofar as such vulnerability is reflected by these acute testing conditions. PMID- 1509710 TI - Recovering heading for visually-guided navigation. AB - We present a model for recovering the direction of heading of an observer who is moving relative to a scene that may contain self-moving objects. The model builds upon an algorithm proposed by Rieger and Lawton, based on earlier work by Longuet Higgins and Prazdny. The algorithm uses velocity differences computed in regions of high depth variation to locate the focus of expansion, which indicates the observer's heading direction. We relate the behavior of the model to psychophysical observations regarding the ability of human observers to judge heading direction, and show how the model copes with self-moving objects in the environment. PMID- 1509711 TI - Responses of cat horizontal cells to sinusoidal gratings. AB - The spatiotemporal properties of cat horizontal (H-) cells were studied by recording the intracellular responses in the optically intact, in vivo, eye to sinusoidal gratings at a photopic mean illumination level. In order to investigate the linearity of spatial summation a "null test" was performed in which the responses to contrast reversal gratings were measured at different positions of the grating relative to the receptive field. Spatial and temporal transfer functions were measured using drifting sinusoidal gratings of variable spatial and temporal frequencies. The amplitudes of cat H-cell responses to contrast reversal gratings modulated with a square wave time-course showed a sinusoidal dependence on spatial phase. When zero crossings of the grating were lined up with the receptive field center, as defined by the maximum of the measured line weighting function, contrast reversal produced no response modulation. This result did not depend on the spatial frequency of the grating or the temporal frequency of contrast modulation over substantial ranges. The response waveform was found not to depend on the spatial phase of the grating. The spatial transfer function of cat H-cells has low-pass characteristics with a cut-off frequency in the range of about 0.4-1.5 c/deg. The shape of the spatial transfer function was roughly the same for temporal frequencies ranging from 3 to 10 Hz. The temporal transfer function exhibited band-pass characteristics with a maximum response amplitude at 3-6 Hz. The amplitude fall-off for low and high temporal frequencies was independent of the spatial frequency of the grating. The results obtained with sine gratings were found not to agree with the receptive field profiles measured with narrow slits flashed at different positions in the receptive field. PMID- 1509712 TI - [Clinical manifestations of insulin resistance. The hormonal-metabolic syndrome X (5H), its prevalence and impact on cardiovascular morbidity and mortality. I]. AB - Insulin resistance (prereceptor, receptor, postreceptor) is a complex phenomenon. It penetrates into the clinical picture via hyperinsulinism as impaired glucose tolerance, or NIDDM, as hyperlipoproteinaemia, arterial hypertension and hirsutism in women (syndrome 5H) associated with the polycystic ovary syndrome or the HAIR-AN syndrome. Based on a group of their 480 patients with NIDDM, 108 women with hirsutism, 320 patients with myocardial infarction and the results of the national cardiovascular programme the authors estimate the prevalence of the 5H syndrome as follows: in the general population 5-10%, in patients with arterial hypertension 15-30%, in NDDM 65-90%, in hirsutic women 10-20% and in patients with myocardial infarction 30-50%. These figures could be, however, substantially higher if as the criterion the IRI response was taken or that of C peptide in OGTT or the results of the hyperinsulinaemic euglycaemic clamp. The clinical 5H syndrome is a phenomenon of latent insulin resistance perceived late by doctors and patients. PMID- 1509713 TI - [Hyperinsulinism as a major etiopathogenic link with arterial hypertension, hyperlipoproteinemia and hirsutism. II]. AB - The authors analyze mechanism by which hyperinsulinism causes NIDDM, hypertension, hyperlipoproteinaemia and hirsutism (5H syndrome). They demonstrate on a group of their 100 patients with NIDDM and arterial hypertension that, as compared with matched pairs without arterial hypertension, they have significantly higher levels of C-peptide and less favourable parameters of dyslipoproteinaemia. Hirsutism occurs in 10-15% of the adult female population, but in 18.4% women with NIDDM. However, in a group of 48 hirsutic women with NIDDM they did not find, as compared with matched pairs (i.e. women with NIDDM of analogous age, BMI and BP) significantly higher C-peptide and lipid levels. According to the authors congenital insulin resistance modified by numerous endogenous and exogenous factors is eventually manifested in the phenotype, in particular via hyperinsulinism as NIDDM, hypertension, associated with dyslipoproteinaemia and obesity which then, as the main risk factors, condition a high cardiovascular morbidity and mortality. Although hirsutism and the polycystic ovary syndrome are associated with hyperinsulinism, their interrelation is probably less close and thus has not such a negative impact on national health. PMID- 1509714 TI - [Diagnosis of syndrome X using comprehensive analysis of the electrical field of the heart]. AB - The authors describe the clinical picture and results of some auxiliary examinations in 18 patients with the X syndrome, i.e. with angina pectoris with a normal angiographic finding on the coronary arteries. For the diagnosis of ischemic cardiac changes, which are an integral part of this syndrome, the authors used a complex analysis of the electric cardiac field by means of a Cardiac 128.1 apparatus (manufactured by ZPA-Cakovice). In patients with the X syndrome they observed a significant reduction of some potential and integral values, as compared with an equally sized group of healthy subjects. On maps of the electric manifestation of cardiac activity on the chest surface ischemic changes were revealed on the antrior and lower cardiac wall but also in its lateral and posterior wall. These changes were older and were found in the subendocardial layer or concurrently in another area of the heart with affection of the subepicardial layer. Minor non-transmural fibroses, most frequently on the septum, in some instances spreading to the anterior and lower cardiac wall, were a surprising finding. At present it is not possible to differentiate merely by analysis of the electric cardiac field the X syndrome and ischemic heart disease. This should be made possible by further comparative studies. The present paper is the first description of ischemic and fibrous cardiac changes in X syndrome diagnosed by a complex analysis of the electric cardiac field in the professional literature published in Czechoslovakia and other countries. PMID- 1509715 TI - [Initial experience with adenosine triphosphate in supraventricular arrhythmia]. AB - The author presents data from the literature pertaining to the possible use of adenine nucleosides in recent years. The main action of adenosine or adenosine triphosphate is focused above all on influencing supraventricular tachycardia which developed as a result of the reentry mechanism. Based on his own observation, the author presents his initial experience with adenosine triphosphate (ATP, Spofa) in different indications: interference with supraventricular tachycardia with slim QRS complexes, interference of tachycardia with wide QRS complexes, termination of atrial flutter in digitalis intoxication and finally induction of an electrocardiographic tracing of latent ventricular preexcitation of the Wolf-Parkinson-White syndrome type. PMID- 1509716 TI - [Immunogenetic study in hypertrophic cardiomyopathy]. AB - Results of assessment of HLA antigens in hypertrophic cardiomyopathies in the world literature are very controversial. Work dealing with this problem in sufficiently large groups of patients is lacking, i.e. work which takes into account different functional and morphological forms of the disease. The authors made therefore a detailed investigation of 60 class 1 and 2 antigens in 117 patients with this disease. Values of the relative risk and chi 2 test revealed a number of possible associations. After correction for the number of examined antigens a significantly higher prevalence was proved only in HLA-B21 in patients with the obstructive form and in patients with advanced myocardial hypertrophy (thickness of more than 30 mm). Examination of HLA antigens can have in the mentioned cases a certain importance during comprehensive examinations of not quite typical forms of the disease. Carriership of antigen B21 is associated with an increased risk of serious cardiological disease, manifested already in young age. PMID- 1509717 TI - [Patients after thyroid gland surgery from the aspect of the endocrinologist]. AB - The authors examined 85 patients after a mean interval of 2.5 years following thyroidectomy. They focused attention on evaluation of the functional state using as criteria the TSH and TRH test. Simultaneously they examined by ultrasonography the volume of the remainder of the thyroid gland. In 8 patients operated on account of carcinoma the average volume of the thyroid gland was 1.3 ml. Five patients were hypothyroid despite permanent substitution. Of 77 patients operated on account of benign goitre evident hypothyroidism was found in 29 (37.7%) and latent hypothyroidism in 14 (18.2%). The volume of the remainder of the thyroid gland in these patients was on average smaller than 4 ml, while in patients who were euthyroid after thyroidectomy the mean volume of the remaining thyroid was more than 4.5 ml. PMID- 1509718 TI - [Ultrasonography in subacute thyroiditis]. AB - The authors draw attention to the altered ultrasonographic (USG) picture of the thyroid gland with subacute inflammation (SAT). A typical finding in the first to third stage of the disease are irregular different sized hypoechogenic to almost echo-void foci with normal parenchyma in between. The finding is normal only in the fourth stage of the disease. In 22 patients before 1987 the USG finding of the thyroid gland was evaluated. In 17 the examination revealed the assumed SAT which was confirmed in 15 patients. Seven patients were at that time hypothyroid. The USG finding was evaluated again in 1990. Ten patients, 2.8 years after the acute stage of SAT had a normal USG finding and were euthyroid. Five patients, not more than one year after the acute stage of SAT had still a pathological USG finding. Four of them were hypothyroid. Based on USG examination it is possible to identify before the cytotogical examination at first ill defined hypothyroidism or hypothyroidism as SAT in stage 1 to 3. PMID- 1509719 TI - [Personal experience with treatment of autoimmune thrombocytopenia using intravenous IgG]. AB - An immunoglobulin preparation for i.v. administration, Ivega (Imuna) was administered to 14 patients, 0.4 g/kg on five consecutive days, but also in lower doses. In all investigated patients a rapid onset of the therapeutic effect was observed--regression of haemorrhage and in 11 a concurrent rise of thrombocytes from a mean value of 20.10(9)/l to mean values of 130.10(9)/l with a maximum between the 6th and 14th day after administration. The tolerance of treatment was satisfactory and no side-effects were observed. PMID- 1509720 TI - [Systemic lupus erythematosus after thymectomy in myasthenia gravis]. AB - The authors describe a case of systemic lupus erythematosus in a 33-year-old female patient who developed the disease 12 years after thymectomy on account of myasthenia gravis. The activity of systemic lupus erythematosus was controlled by pulsed treatment with methyl prednisolone followed by long-term oral glucocorticoid and immunosuppressive therapy. The authors discuss the risk of systemic lupus erythematosus after thymectomy on account of myasthenia gravis with regard to the HLA haplotype. PMID- 1509721 TI - [A fistula between the aorta and esophagus--an uncommon sequela of dissection of the thoracic aorta]. AB - In a patient with repeated dissection of the ascendent aorta where the first episode was resolved surgically by an intraluminal prosthesis the authors describe the rare consequence of the development of a new dissection manifested by an aorto-oesophageal fistula. In the described case an inoperable episode was involved which fully confirmed the clinical validity of the pathognomic Chiari triad. PMID- 1509722 TI - [Tumor microembolization in the lungs--a cause of marked dyspnea, syncope, hemolytic syndrome and disorders of hemocoagulation]. AB - The authors describe the course of the disease in a 28-year-old woman who suffered two years following surgery of breast cancer from rapidly deteriorating dyspnoea, syncopes and laboratory manifestations of global respiratory insufficiency. The finding on auscultation of the lungs was normal, pulmonary angiography did not reveal signs of serious pulmonary embolization. The patient died after ten days in hospital despite comprehensive therapy and artificial ventilation. Necropsy revealed multiple microembolizations of tumourous cells into the pulmonary vessels as the main causes of the disease. Concurrently infiltration of the bone marrow by tumourous cells was revealed. The course of the disease was complicated by impaired haemocoagulation as a result of microangiopathic haemolytic anaemia and disseminated intravascular coagulation during the passage of erythrocytes through the pathologically altered pulmonary capillaries and impaired liver function. PMID- 1509724 TI - Covering the uninsured: no-frills insurance comes to West Virginia. PMID- 1509723 TI - [Circulating heparin-like anticoagulant--2 cases of successful therapy]. AB - In the circulation of patients with severe haemorrhagic conditions in rare instances an anticoagulant of heparin nature can be detected, the exact origin of which has not been elucidated so far. These patients can be treated by protamine sulphate. The authors present their own observations in two women where the circulating anticoagulant of heparin nature was detected during a haemorrhagic condition after spontaneous rupture of an enlarged spleen and in scleroderma with organ affection. In both instances treatment was successful. PMID- 1509725 TI - The use of head-up tilt table testing in the evaluation of unexplained syncope. AB - Head-up tilt table testing was performed in 50 patients for evaluation of syncope. A positive test occurred in 29 patients (58 percent). Of these 29 patients, 15 were categorized as vasovagal; 11 as orthostatic hypotension; and three as chronotropic incompetence. Isoproterenol facilitated the occurrence of a positive test in 13 patients. Medications were used to treat 15 of the 29 patients having a positive test result. Syncope recurred in two patients over a 9 +/- 5 month follow-up period. In patients having unexplained syncope, head-up tilt table testing may provide a diagnosis and can be used to assess therapy. Earlier use of this testing modality in selected patients may obviate more expensive testing. PMID- 1509726 TI - Pyomyositis in a diabetic host. AB - A case of pyomyositis in a diabetic host is presented. Pyomyositis is occurring more often and clinicians must be aware of this entity, especially in the immunocompromised host. The reasons for more frequent and severe infections in the diabetic patient are outlined. PMID- 1509727 TI - The "right" to health care. PMID- 1509728 TI - PHS training grant to enhance rural health education efforts. PMID- 1509729 TI - Nursing care makes a difference. PMID- 1509730 TI - Perimenstrual symptoms and health-seeking behavior. PMID- 1509731 TI - Health promotion and life satisfaction in elderly black adults. PMID- 1509732 TI - Adjusting to the nursing home. PMID- 1509733 TI - Visitors' verbal behavior with coronary care unit patients. PMID- 1509734 TI - Role performance and job satisfaction of school nurses. PMID- 1509735 TI - Computer-aided management of urinary incontinence in nursing homes. PMID- 1509736 TI - Role theory and parent-infant interaction. PMID- 1509737 TI - Incentives and rewards for subjects in nursing research. PMID- 1509738 TI - A typology of data collected in naturalistic interviews. PMID- 1509739 TI - [Economic aspects of therapy for lipid metabolism disorders]. AB - The primary and secondary prevention of cardiovascular diseases and, therefore, the therapy of hyperlipidemia is essential in strategies to lower morbidity and mortality from coronary heart disease (CHD), the most relevant atherosclerosis associated disease. These programs imply not only a medical but also an economic challenge to our health system. That is why all therapeutic measures have to be evaluated regarding their cost-effectiveness. A cost-effectiveness profile was calculated for all the therapies of hyperlipidemia (nutritional therapy, dietetic nutritionals, drugs and LDL-apheresis) with respect to the following parameters: total cholesterol, LDL-cholesterol, HDL-cholesterol and triglycerides. The daily costs of all interventional measures are compared to the success rate, whereby an index of daily therapy costs and 1% change per lipid parameter was calculated. Nutritional therapy is by far the cheapest, and LDL-apheresis the most expensive but also the most effective and reliable therapeutic measure. It has to be considered, however, that dietary intervention can be very successful in overnutrition while in rare cases of severe homozygous familial hypercholesterolemia there is no therapeutic alternative to LDL-apheresis. Life style modifications, such as changing nutritional habits, may contribute towards reducing or removing one or more risk factor(s) (e.g. malnutrition is associated with overweight, hyperlipoproteinemia (HLP), hyperinsulinemia (syndrome X), hyperfibrinogenemia and hypertension). But neither health politicians nor the population seem to be conscious of the fact that life-style changes help to reduce medical expenditure. Considering the fact that nearly every medical service is getting more and more expensive, the need to introduce financial regulations is evident.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1509740 TI - Alterations of antioxidant tissue defense enzymes and related metabolic parameters in streptozotocin-diabetic rats--effects of iodine treatment. AB - This study reports on the effect of streptozotocin (STZ) induced diabetes on water soluble-SH and -SS, as well as on hepatic glutathione peroxidase (GSH-Px), catalase and superoxide dismutase (SOD) activity and on malondialdehyde (MDA) content. In addition, we determined serum concentrations of glucose, cholesterol, triglycerides and thyroxine, and thyroid weight. To elucidate the possible impact of exogenous iodine on impaired free radical tissue defense mechanisms STZ diabetic rats were exposed to iodine brine providing for a daily iodide uptake of about 300 micrograms/kg body weight. STZ-exposure caused a decline in thyroid weight (p less than 0.01) and in total serum thyroxine (p less than 0.001), as well as a fall in hepatic catalase (CAT) activity (p less than 0.01) versus control group. Impairment of catalase activity was related to serum glucose level (r = -0.569, p less than 0.01), while hepatic MDA was positively related to serum glucose (r = + 0.5, p less than 0.01). No protective effects of iodine brine were seen with regard to impairment by STZ of antioxidant enzyme status. We conclude that impairment by STZ of antioxidant enzymes may contribute to STZ-dependent experimental diabetes. PMID- 1509741 TI - [Alcoholic ketoacidosis--3 episodes in one patient]. AB - 3 episodes of alcoholic ketoacidosis were observed in one female patient over a period of 19 months. The clinical picture consisted of vomiting, dehydration, hyperventilation and abdominal pain. Predominant laboratory findings were acidosis (pH less than 7) and hyperglycaemia, with blood glucose values of 354, 330 and 147 mg/dl. This disorder is an important cause of metabolic acidosis, but especially in the German literature there are only rare reports on this issue. The picture of ketoacidosis in mostly chronically malnourished alcoholics reflects not only the complex abnormalities of acid-base balance caused by excessive cumulation of ketoacids, but also the related severe depletion of electrolytes and extracellular volume. Adequate acute therapy (as for diabetic ketoacidosis) and thorough follow-up treatment of any concurrent conditions result in rapid reversal of the syndrome in most cases. Since there are few reports of repeated episodes in one patient, an overview of this disorder is presented concerning management and differential diagnosis of the basis of our case report. PMID- 1509742 TI - [Gliadin IgA antibodies in diagnosis of celiac disease in childhood]. AB - An enzyme immunoassay kit for the determination of anti-gliadin-IgA antibodies in serum has been evaluated in the diagnosis of coeliac disease in childhood. 84 patients, 22 of them with coeliac disease according to ESPGAN's criteria were tested between 1978 and 1989 and the results have been correlated with the findings on small intestine biopsy and the clinical features. The sensitivity of the test was 95.5% and the specificity was 87.0% on initial diagnosis. On a gluten-free diet reduced antibody levels were seen in all patients. During gluten challenge 11 of 13 children showed an increase in anti-gliadin-IgA concentration. Of the remaining 2 without antibody elevation IgA deficiency became manifest in one patient, the other had a nearly normal mucosa on small intestine biopsy. Provided that IgA deficiency is ruled out and the gluten intake is sufficient the test seems to be useful for screening and might replace biopsy after gluten challenge in cases of increasing antibody levels. PMID- 1509743 TI - [Radioimmunologic study of the circadian rhythm of cortisol and melatonin in saliva]. PMID- 1509744 TI - [Interactions between calcium and phosphorus administration and vitamin D metabolites in premature infants]. PMID- 1509745 TI - Therapeutic drug monitoring and pharmacokinetic dose prediction methods. AB - Therapeutic drug monitoring is recommended in suspected drug overdosage, in cases of therapeutic failure, in the establishment of regimens in patients with altered pharmacokinetics and in patients with unknown previous medications. Pharmacokinetic dose prediction methods have been developed allowing individual dosage adaptation. As examples, the three-point method of Sawchuk and the Bayesian technique are described. Drug concentrations could be predicted with sufficient accuracy by use of the three-point method in critically ill patients treated with aminoglycosides or flucytosine. Bayesian forecasting proved to be useful in predicting the nocturnal concentration curves in patients with asthma treated with a sustained-release preparation of theophylline for once-daily dosage. The efficiency of drug treatment can be considerably improved by monitoring serum drug concentrations and individualizing dosage using pharmacokinetic methods. PMID- 1509746 TI - Clinical relevance of the determination of antiepileptic drugs in serum. AB - Opinions on the clinical relevance of the determination of antiepileptic drugs in serum are very divergent. Specially the value of routine determinations has not been clarified up to now. At present the determination of antiepileptic drugs is indicated in the following situations: resistance to therapy including suspected irregular intake, adjustment of the serum level into the therapeutic range to prevent under- or overdosage, suspected intoxication (particularly during combined therapy), dosage monitoring when changes in the dosage-serum level relationship might occur, combined therapy, dosage reduction in the absence of seizures, determination of a baseline level in patients with good anticonvulsant control, legal indications, therapy research. PMID- 1509747 TI - Therapeutic drug monitoring for the 1990s: meeting the laboratory needs of a changing environment. AB - The need for monitoring serum and plasma concentrations for therapeutic drugs given to hospitalized and outpatients will continue to growth during the next few years, both in terms of the number of tests ordered each year and the number of different drugs that are monitored. The clinical laboratory will play an important role in implementing and maintaining accurate, cost-effective drug monitoring and treatment programs. To meet changing needs, further development and evaluation of automated analytical assays will be necessary. PMID- 1509748 TI - Analyses of the pattern of therapeutic drug monitoring in a university hospital laboratory. Suitability and performance of the CEDIA assays. AB - New homogeneous enzyme immunoassays (CEDIA assays) for therapeutic drug monitoring were evaluated on Boehringer Mannheim/Hitachi 704. A fluorescence polarization immunoassay and HPLC were chosen as comparison methods. A good correlation of patient data was observed for both methods (slopes 1.033-1.167). Imprecision within-run and between-day as well as the recovery in control samples of an external quality control survey were excellent and comparable to the routine method. In order to optimize the use of the CEDIA assays also for parameters which are less frequently requested, a parameter-setting for the batch analyzer COBAS Fara was worked out. Performance of the CEDIA assays on random access analyzers is discussed with regard to the background of a laboratory for clinical chemistry in a University Hospital. PMID- 1509749 TI - Liquid chromatographic analysis of phenobarbital, phenytoin, and theophylline. AB - Sera from the routine of therapeutic drug monitoring were assayed for phenobarbital, phenytoin, and theophylline with three different methods: fluorescence polarization immunoassay as the standard procedure, the new CEDIA assays within a multicenter evaluation and HPLC which is known to yield results with a high specificity. CVs for between-day imprecision ranged from 2.6-8.6%, depending on the concentration of the drugs. There was a tendency to lower CVs for the HPLC procedure. Accuracy was verified with commercial control materials and spiked sera and proved to be satisfactory for all three methods and parameters. The linear range was approx. twice as wide for the HPLC compared with the other methods. The method comparisons were quite favorable. Deviations occurred mainly in the subtherapeutic concentration range. PMID- 1509750 TI - The dosage alone determines whether a substance is toxic. PMID- 1509751 TI - Results of the multicenter evaluation of the CEDIA Theophylline assay. AB - We report on the results of the multicenter evaluation of the CEDIA Theophylline assay on Boehringer Mannheim/Hitachi analyzers in 15 clinical laboratories in Europe and U.S.A. Main items of investigation were imprecision, recovery of control sera, interlaboratory survey and method comparisons using patient samples. Imprecision was found to be comparable to other routine methods. An advantage of the CEDIA assay can be seen in the good interlaboratory transferability of results. The new test has been shown to measure very accurately particularly by comparison with HPLC procedures revealing highly correspondent results. The reagent can be used up to one month using multiple recalibration. Due to its high practicability and reliability the CEDIA Theophylline assay can be recommended as a very suitable routine method for therapeutic drug monitoring on random access analyzers like Boehringer Mannheim/Hitachi analysis systems. PMID- 1509752 TI - Results of the multicenter evaluation of the CEDIA Phenytoin assay. AB - Thirteen clinical evaluation sites in Europe and U.S.A. investigated the CEDIA Phenytoin assay on Boehringer Mannheim/Hitachi analyzers with respect to imprecision, recovery of control sera, interlaboratory survey, linearity and method comparisons using patient samples. The linear dose-response relationship up to 40 micrograms/mL was confirmed by all participants. Imprecision at therapeutic analyte concentrations equalled that of other routine methods. Recovery of controls was found in a +/- 6% range for target values assigned by the CEDIA assay. The good interlaboratory transferability of the CEDIA assay was confirmed with control material and human samples. The reconstituted reagent can be used up to one month using weekly recalibration. In method comparison studies good correlations to other routine methods were obtained. Results in analyte-free human sera did not deviate systematically from the zero-point. Thus, the accuracy in patient sera has been shown for the CEDIA Phenytoin assay. PMID- 1509753 TI - Results of the multicenter evaluation of the CEDIA Phenobarbital assay. AB - The CEDIA Phenobarbital assay has been evaluated in twelve clinical laboratories in Europe and U.S.A. on Boehringer Mannheim/Hitachi analysis systems. The evaluation focused on the analysis of imprecision and accuracy. Within-run and between-day coefficients of variations of the new assay were comparable to those of established routine methods. As demonstrated in an interlaboratory survey study with controls and human sera, results obtained in different laboratories showed a good agreement. The CEDIA Phenobarbital assay measured very accurately, as particularly confirmed by comparison with HPLC. It can be recommended as a reliable and practicable test for monitoring of phenobarbital on Boehringer Mannheim/Hitachi analyzers used in routine clinical chemistry. PMID- 1509754 TI - Practical aspects of monitoring cardiac drugs in the blood. AB - Various factors known to affect digoxin blood values are discussed in the present review. A reduction as well as an increase in digoxin levels may be due to the method employed, to errors in the preanalytical phase, to peculiarities of the patient, to diseases or to the administration of drugs. Increased digoxin concentrations above the therapeutic range are much more common than manifestations of digoxin intoxication. However, geriatric patients are specially sensitive to intoxication. Attention has to be paid to digoxin-like immunoreactive factors (DLIF) being synthesized under certain physiologic and pathophysiologic conditions which cause falsely elevated values in digoxin immunoassays. The determination of digoxin levels is indicated in suspected intoxication or hypersensitivity to digoxin, in patients with pacemakers or those receiving certain drugs, in old people and in patients suffering from any concomitant disease. The time of blood collection has to be carefully controlled in order to determine digoxin concentrations of diagnostic value, the physical activity of the patient being a main influencing factor. PMID- 1509755 TI - CEDIA--homogeneous immunoassays for the 1990s and beyond. AB - New homogeneous enzyme immunoassays have been developed for cortisol, digoxin, digitoxin, theophylline, phenytoin, and phenobarbital using the cloned enzyme donor immunoassay technology. As applied to Boehringer Mannheim/Hitachi analysis systems these methods provide rapid, accurate and precise quantification of analytes, with minimal interferences from endogenous serum constituents and low cross-reactivities to structurally-related hormonal precursors, drug metabolites and natural compounds. Additional significant features of the new assays are linear standard curves and two-point calibration. The six CEDIA assays join the two currently available CEDIA assays for determination of the thyroid parameters T4 and T Uptake. Additional new therapeutic drug and anemia monitoring assays are under development, demonstrating the versatility of the cloned enzyme donor immunoassay technology. These tests, in concert with Boehringer Mannheim/Hitachi analyzers, provide a high throughput, random access immunoassay system. The menu of available assays should continue to increase during the 1990s, providing efficient automation while allowing consolidation of testing on a limited number of instrument systems. PMID- 1509756 TI - Improving the specificity of digoxin immunoassays. AB - The overall reliability of measuring digoxin in serum improved significantly with the discovery and application of immunoassays. However, because of the low concentration of digoxin being measured, its narrow therapeutic range in serum, and the presence of endogenous digoxin-like immunoreactive factors (DLIF), developing assays for measuring digoxin still pose formidable challenges. In this presentation, recent developments in the characterization of DLIF from bovine adrenal cortex and human serum are described. Data accumulated to date suggest there is one principal endogenous molecular factor (DLIF) in humans that cross reacts with anti-digoxin antibodies. This factor exists at sufficiently high concentrations in some patients to interfere with measurements of digoxin by most digoxin immunoassays. All digoxin immunoassays should be tested to interference from this endogenous factor. Various techniques for reducing DLIF cross reactivity are reviewed. The isolation and purification of DLIF now provides new approaches for selecting specific anti-digoxin antibodies used in developing more accurate digoxin immunoassays. PMID- 1509757 TI - Endogenous digoxin-like immunoreactive factors (DLIF) as measured by the CEDIA digoxin assay and a fluorescence polarization immunoassay. AB - The sensitivity of a new homogeneous enzyme immunoassay for the determination of digoxin (CEDIA Digoxin assay) and a fluorescence polarization immunoassay (FPIA) to interference by digoxin-like immunoreactive factors (DLIF) was studied in sera from pregnant women, newborns, patients undergoing hemodialysis and patients with renal insufficiency, but without hemodialysis. None of the patients had been treated with digoxin or digitoxin. Cross-reactivity of DLIF in the CEDIA assay was generally lower than in the FPIA. Data on the distribution DLIF of values and method comparisons showed that sera of the four patient groups reacted in a completely different way in both assays, suggesting that the nature of DLIF in the four groups is not identical. Addition of digoxin to sera of patients not treated with this drug resulted in a reduction of the apparent DLIF concentration in the CEDIA assay and the FPIA. This shows that DLIF interference may be less pronounced in sera of patients undergoing digoxin therapy compared to untreated persons. Although the CEDIA assay is less sensitive to DLIF interference than the FPIA, further efforts are needed to reduce the extent of this interference. PMID- 1509758 TI - Evaluation of the CEDIA digoxin assay on Boehringer Mannheim/Hitachi 717 analyzer. AB - Some aspects of a new homogeneous enzyme immunoassay for the determination of digoxin have been evaluated, as part of a multicenter project. The CEDIA Digoxin assay is based on the use of two beta-galactosidase fragments (EC 3.2.1.23) produced by recombinant DNA techniques, one of them linked to digoxin. These two fragments couple to form the complete active enzyme, if not hindered by anti digoxin antibodies. Digoxin in serum competes for antibody binding. The procedure can easily be automated and does not require special equipment. The imprecision of the method was studied at three different concentration levels (0.56, 1.29 and 2.77 ng/mL of digoxin). Within-run coefficients of variation were 8.01%, 5.57% and 3.30%, respectively, the corresponding between-day CVs being 17.4%, 8.41% and 4.89%. The procedure was found to be linear up to 4.4 ng/mL. Reagents were stable for at least four weeks. Results obtained by the CEDIA Digoxin assay compared well with those obtained by fluorescence polarization immunoassay. PMID- 1509759 TI - Results of the multicenter evaluation of a novel homogeneous immunoassay for digoxin based on the cloned enzyme donor immunoassay technology. AB - A new CEDIA assay for the measurement of digoxin in serum on random access analyzers was evaluated by twelve laboratories in Europe and the United States. Studies on the analytical range, reproducibility, calibration stability, recovery in controls, interlaboratory comparability, comparability with routine methods, and the effect of various interfering factors have been performed and the results are presented in this paper. The analytical performance was comparable to that of routine methods provided the manual pipetting step for pre-incubation was performed with accurate pipettes. A major advantage of the CEDIA Digoxin assay in terms of convenience is the simple two-point calibration procedure. Moreover, digoxin can be determined within 15 minutes after receiving the samples on random access analyzers like Boehringer Mannheim/Hitachi analysis systems. Thus, the CEDIA Digoxin assay represents an attractive alternative to the measurement of digoxin on dedicated immunochemical assay systems. PMID- 1509760 TI - Results of the multicenter evaluation of a homogeneous immunoassay for digitoxin based on the cloned enzyme donor immunoassay technology. AB - We evaluated a CEDIA assay for the determination of digitoxin in serum on random access analyzers. The multicenter evaluation included studies on the analytical range, calibration stability and reproducibility of the new assay. Moreover, recovery in controls, transferability of results obtained in different laboratories, comparability with routine methods, and the effect of various interfering factors have been analyzed. Summarized the analytical performance was comparable to that of routine methods. The CEDIA Digitoxin assay represents an attractive alternative to established digitoxin immunoassays because it can be performed on random access analyzers, thus permitting the simultaneous determination of digitoxin and other serum analytes without sample splitting. PMID- 1509761 TI - An evaluation of a non-isotopic homogeneous enzyme immunoassay (CEDIA assay) for cortisol and its clinical utility. AB - Serum cortisol is one of the more frequently requested steroid hormone assays. Its use is important in evaluating diseases of the adrenal cortex and pituitary. We briefly review the biochemistry of cortisol synthesis, the pathophysiology resulting from adrenal and pituitary abnormalities and the more specific immunochemical procedures which have replaced colorimetric chemical assays for cortisol. We also report our results on the evaluation of the analytical performance of the non-isotopic homogeneous CEDIA Cortisol assay and compare the advantages of this assay to state-of-the-art immunoassays. PMID- 1509762 TI - Results of the multicenter evaluation of the CEDIA cortisol assay. AB - The present paper describes the multicenter evaluation of the CEDIA Cortisol test for total cortisol. The observed linearity of the test was between 1.2 and 50 micrograms/dL cortisol. The limit of detection was calculated as 1.2/dL. Imprecision studies covering the diagnostically relevant range (5-20 micrograms/dL cortisol) yielded coefficients of variation between 1.7-8.9% (within-run) and 2.7-10.5% (between-day). An interlaboratory survey using 41 human samples and three control sera demonstrated that the new CEDIA Cortisol assay has a good interlaboratory transferability. Method comparison studies between the CEDIA Cortisol test and EIA, FIA, FPIA, and various RIAs yielded an acceptable level of agreement and concordant results in most cases. Low cross reactivity of the antibody used in the new cortisol assay was observed with precursors or metabolites of cortisol. Especially, dexamethasone did not cross react. However, prednisolone, 6-methylprednisone, and corticosterone showed cross reactivities. No limitation by endogenous interferences was observed. The CEDIA Cortisol assay permits the precise, fast and sufficiently specific determination of cortisol. Furthermore, it offers the advantages of a non-radioactive assay and can be performed conveniently on Boehringer Mannheim/Hitachi analyzers in combination with routine clinical chemistry. PMID- 1509763 TI - Economic aspects of therapeutic drug monitoring. AB - In the last two decades two major trends heavily influenced the situation of the clinical laboratories. Cost saving issues have become more and more significant and an exploding number of tests has to be performed by a limited number of technicians. The latter task is facilitated by the use of automated analyzers. The CEDIA assays for therapeutic drug monitoring (TDM) can be performed on Boehringer Mannheim/Hitachi systems used for routine clinical chemistry. This means that now it is possible to determine all parameters of clinical chemistry, proteins, and TDM without sample splitting on one analyzer, resulting in saving of manual workload and costs. PMID- 1509764 TI - [Brief definition of medical ethics concepts. 21]. PMID- 1509765 TI - [Differential diagnosis of peptic ulcer]. AB - Although new pathogenetic findings of peptic ulcers have been detected, there still remain some open questions. Accurate anamnestic evaluation will find out risk factors as cigarette-smoking, stress and therapy with nonsteroidal antiinflammatory drugs (NSAIDs), and will be helpful in differential diagnosis. Endoscopy is the diagnostic means of choice, and enables to easy helicobacter pylori detection. Since some gastric ulcers are actually carcinomas, it is absolutely necessary to obtain multiple biopsies. The Zollinger-Ellison syndrome and symptoms of other rare diseases of the upper intestine are discussed. PMID- 1509766 TI - [Helicobacter pylori. New apsects in the pathogenesis of peptic ulcer disease]. AB - Antral gastritis and peptic ulcer disease are closely related to gastric Helicobacter pylori (HP) infection. HP possesses several pathogenic features which point to a causal role of HP in the development of gastroduodenal lesions. It is now generally accepted that HP causes type B gastritis, while its role in the pathogenesis of peptic ulcers is still unsolved. According to the classical ulcer concept, peptic ulceration is the result of an imbalance between protective mucosal mechanisms and aggressive digestive factors. The identification of HP does not disprove this concept, however, HP has to be added as a major pathogenic factor. PMID- 1509767 TI - [Methodology and clinical significance of intragastric long-term pH measurement]. AB - Intragastric long-term pH-metry is a suitable method of assessing gastric acidity under conditions of real life. The pH-metry system consists of three components: pH electrode, solid state recorder, and data analyzing system. Combined glass electrodes are recommended for gastric pH studies. Up to now, there are no generally accepted normal values in gastric pH-metry and thus data analyzing is not uniformly standardized. Intragastric pH-metry is the method of choice for monitoring of antisecretory treatment. This method enables the recognition of non responders and improves dosing of antisecretory drugs. The prognostic value of gastric pH-metry in the assessment of acid-related diseases, if any, has still to be defined. PMID- 1509768 TI - [Current therapy of ulcer disease]. AB - It is generally accepted that ulcer pathogenesis is mainly mediated by an imbalance between aggressive factors as gastric acid and pepsin, and obviously genetically determined defects in protection mechanisms of the gastric and duodenal mucosa. Since at present it is not possible to substitute these defects properly by pharmacological measures, the modern ulcer therapy aims to a distinct acid reduction as the main and most successful therapeutic principle. Recent studies show a direct correlation between the effectiveness and the acid reducing potency of a given anti-ulcer drug, assessed by pH above 3 over time. By long term treatment using H2-blockers and most recently the ATPase inhibitor Omeprazole it is now possible to reduce drastically the relapse rates of gastrointestinal ulcers and to improve significantly quality of life. An effective prophylaxis in duodenal ulcer can also be achieved by combination therapy with bismuth plus antibiotics or with omeprazole plus antibiotics. Even ulcers induced by nonsteroidal-antirheumatic drugs or acetylsalicylate can be adequately treated and prevented by acid reducing drugs. The present article includes pathophysiological and pharmacological backgrounds of medical ulcer therapy as well as guidelines for indication and mode of application of the different antiulcer drugs concerning short and long term treatment. PMID- 1509769 TI - [Complications of peptic ulcer]. AB - The complication rate of peptic ulcer disease is 2 to 5% a year. Hemorrhage occurs four times more often than perforation and penetration. High age and the use of nonsteroidal antiinflammatory drugs (NSAID) are the most important risk factors. The incidence of rebleeding is twice as high after a first complication. About 15 to 30% of bleeding patients die because of this complication. Endoscopy is the means of choice in diagnosis and primary therapy. Gastric retention and vomiting of stale food are typical symptoms of gastric outlet obstruction. PMID- 1509770 TI - [Surgical treatment of stomach and duodenal ulcer]. AB - Despite lots of innovation in conservative treatment, surgery has established in ulcer therapy. Elective surgery shows a very low mortality rate whereas that of emergency operations is approximately ten times that high. If one intends to improve the currently insufficient results of ulcer treatment, this is only possible by decreasing the number of emergency operations which for many years remains on a nearly unchanged level, in favour of elective surgery. This especially is true for patients on high risk regarding an ulcer complication. Most important complications are recurrent phases within short time and poor compliance. A further complication is any critical factor in general which leads to the assumption that an appearing ulcer complication may most likely not be survived. Critical factors mainly are advanced age and attendant cases of illness. It may be expected that the still high mortality of this benign disease can be considerably reduced by applying the formula "more elective--less emergency surgery". PMID- 1509771 TI - [Theodor Billroth--a short biography]. PMID- 1509772 TI - [Abortion in the penal code]. AB - Before discussing the change of legal norms it is necessary to know the actual law. The paper shows the West-German penal code and it's application in respect of the pregnant women, the physician and third persons. PMID- 1509773 TI - [Legal protection of the fetus in West Germany]. AB - No German legislation specifically addresses legal protection to the unborn child. Abortion which is synonymous with killing an unborn child remains a crime respective if prosecution is carried out or not. The German Supreme Court produced guidelines in 1975 concerning the unborn child's protection which indicate that the life of the unborn should be afforded the same legal protection as that of a living being. But jurisdiction, new legal drafts or the public debate alone are not able to reduce the number of abortions. PMID- 1509774 TI - The effect of alcohol consumption on body weight among Wisconsin adults. AB - It is a common perception that alcohol use increases body weight. In fact, people are often advised to reduce their drinking if they wish to lose weight. To assess the relationship between alcohol use and body weight, we analyzed data from 5,496 Wisconsin men and women. We compared weights of drinkers and non-drinkers and adjusted for potential confounders. For women, there was a strong inverse relationship between drinking and weight. Women who drank any alcohol weighed an average of 2.6 kg (5.6 lbs) less than women who did not drink (p less than .0001). This association was found for all types of alcoholic beverages. No difference in weight was found overall between drinking and non-drinking men, although men who drank wine weighed significantly less (1.8 kg, p less than .05) than non-drinkers. These results, combined with other recent studies, suggest that alcohol use does not lead to increased weight among Wisconsin adults, and may be associated with lower weight among women. PMID- 1509775 TI - Adolescent suicide: an analysis using Erikson's developmental framework. PMID- 1509776 TI - Health care reform's future: the road less traveled. PMID- 1509777 TI - The adventure continues. PMID- 1509778 TI - The search for our future. PMID- 1509779 TI - The fallacy of health care. PMID- 1509780 TI - Plasma and tissue alterations of peptide YY and enteroglucagon in rats after colectomy. AB - Peptide YY (PYY) and enteroglucagon are produced by endocrine cells of the colonic mucosa. PYY inhibits upper gastrointestinal motility, and enteroglucagon is trophic for small bowel mucosa. Adaptive increase in the production and release of these peptides may improve functional results after colorectal resections. We hypothesized that if segments of the colon were resected, then production and release of PYY and enteroglucagon would increase in the remaining segments of bowel. Animals which underwent colonic transections and partial resections had transient elevations of PYY up to 250 +/- 80 pmol/L, which dropped to control group levels in the second week following surgery. Rats with an abdominal colectomy had significantly greater PYY levels than all other groups from the third (208 +/- 30 pmol/L) to the thirty-eighth (100 +/- 16 pmol/L) week of the study. Circulating levels of enteroglucagon were elevated to 156 +/- 35 pmol/L in rats with a right hemicolectomy during the first week following surgery. Enteroglucagon levels did not significantly vary in the other groups studied. Both tissue PYY (413 +/- 33 pmol/gram) and tissue enteroglucagon (171 +/ 17 pmol/gram) were significantly elevated in the rectums of the rats with an abdominal colectomy, as compared to all other groups. The elevated tissue levels may thus account for the ability to maintain elevated plasma PYY. Double immunogold labeling of endocrine cells in the colorectal tissue for PYY and enteroglucagon revealed both peptides within the same endocrine cells and secretory granules. These studies support the hypothesis that circulating levels of PYY are elevated after major colonic resections and suggest that L-type endocrine cells may participate in adaptive responses which improve intestinal function following colonic surgery. PMID- 1509781 TI - Biological and clinical aspects of autoimmune inner ear disease. AB - The clinical presentation, diagnosis, and management of autoimmune inner ear disease are reviewed. Recent studies indicating an autoimmune etiology and pathogenesis are discussed, along with a comparative analysis of several promising new animal models. Further studies to define the natural history, pathogenesis, and diagnosis of the disease are suggested. PMID- 1509782 TI - Use of Xenopus laevis frog egg extract in diagnosing human male unexplained infertility. AB - Approximately one in six married couples find themselves involuntarily infertile. This ratio translates to between two and four million U.S. couples. Although numerous tests are available for diagnosing infertility problems, 5-10 percent of all couples who seek medical treatment are diagnosed with unexplained infertility. Several tests are presently available for diagnosing male infertility; however, none of the present procedures test for activation of the sperm nucleus following entry into the fertilized egg, a series of events critical for the entry of the zygote into the developmental program. We have developed an in vitro human sperm activation assay, using Xenopus laevis frog egg extract. When normal human sperm is permeabilized and then mixed with frog egg extract, the sperm nuclei decondense, synthesize DNA, and recondense during a three-hour time course. We have tested this assay's utility in diagnosing previously unexplained infertility. We found that 20 percent of the male infertility patients produced sperm that responded abnormally in the assay (95 percent confidence interval, 4-48 percent; n = 15), while sperm samples from 15 fertile males showed no abnormal responses (p = 0.0112). These preliminary results indicate that the human sperm activation assay may be a useful tool for diagnosing some cases of human infertility. PMID- 1509783 TI - Cheyne-Stokes respiration in congestive heart failure. AB - Cheyne-Stokes respiration is an abnormal breathing pattern which commonly occurs in patients with decompensated congestive heart failure and neurologic diseases, in whom periods of tachypnea and hyperpnea alternate with periods of apnea. In the majority of these patients, the ventilatory patterns may not be recognized, and the clinical features are generally dominated by the underlying disease process. Cheyne-Stokes respiration may, however, have profound effects on the cardiopulmonary system, causing oxygen desaturation, cardiac arrhythmias, and changes in mental status. Treatment of Cheyne-Stokes respiration in congestive heart failure with supplemental oxygen or nasal continuous positive airway pressure, in addition to conventional therapy, may improve the overall cardiac function and perhaps the patient's prognosis. PMID- 1509784 TI - [Long-term follow-up of Crohn disease]. AB - 184 patients diagnosed with Crohn's disease were observed for an average of 5 years and evaluated for clinical pattern and course of disease. The male/female ratio was almost equal (90 m. vs. 94 f.). The peak of disease manifestation was between years 18-32. Familial clustering of inflammatory bowel disease was observed in 2.2%. The pattern of anatomic involvement was ileocolic in 53%, colon in 24%, small bowel in 20% and other locations in 3%. 34% of patients were afflicted with at least one extraintestinal manifestation, 34% developed fistulae. Fistula formation was seen more often in colon involvement than small bowel involvement (69% vs. 32%). 48% of the patients were operated at least once. 3 patients died during the observation period, 2 of them with sepsis. Evolution of carcinoma was not observed. Some of our results are in accordance with the literature, some distinct observations (e.g. low familial clustering) underline the theory of a multifactorial pathogenesis in Crohn's disease. PMID- 1509785 TI - Percutaneous transhepatic dissolution of gallbladder stones. AB - The method of percutaneous transhepatic dissolution with methyl tert-butyl ether (MTBE) has been used at the Zagreb Clinical Hospital Department of Medicine since 1989. From December 1989 until December 1991, 69 patients, 51 (74%) females and 18 (26%) males, with symptomatic and cholesterol gallbladder stones were hospitalised at the Department. All patients preferred percutaneous transhepatic dissolution to surgical treatment of gallbladder stones. The gallbladder was successfully punctured and the catheter placed into the gallbladder lumen in 63 (91%) patients, whereas complete dissolution was achieved in 59 (85.5%) patients. In 21 (33.9%) of these 59 patients, after completed dissolution computer processed roentgenograms and ultrasonic scan of the gallbladder revealed residual particles of debris sized up to 2 mm. Six patients in whom puncture, i.e. the placement of the catheter into the lumen was unsuccessful, were electively operated on the following day without any complications. The mean duration of hospitalisation for 63 patients was 4.5 days. PMID- 1509786 TI - [Surgical therapy of acute cholecystitis--advantages of early operation]. AB - 229 patients with an acute cholecystitis were operated on at the Surgical University Hospital of Ulm between 3/1982 and 6/1990. 42.3% of the patients were older than 70 years, the mean age being 64.3 years. 51.5% suffered from a complicated form of the disease. Intercurrent diseases were preoperatively found in 76%. Intraoperative complications of a technical nature occurred in 3.1%. The overall postoperative morbidity rate was 54%, with 9.4% of local problems, and showed a clear dependency on age and the number of preexisting risk factors. 31% had to undergo reoperation. The overall mortality rate was 2.6%, with a 0% mortality for patients under 65 years. The number of preexisting risk factors clearly correlated the period of hospitalisation, which was 16.1 days on average. In symptomatic gallstone diseases an early elective cholecystectomy should be strongly considered, especially in aged and multimorbid patients. PMID- 1509787 TI - [Endosonography in gastroenterology--an intermediate evaluation]. AB - Endoscopic ultrasonography has widened the diagnostic spectrum of gastrointestinal disorders in two respects: For the first time it became possible to visualize the gastrointestinal wall with its layer structure. EUS was shown to be highly accurate in the local staging of gastrointestinal tumors (T and N stage). The clinical relevance of endosonography derives from stage-dependent treatment protocols selecting patients for different forms of tumor therapy. The second advantage of endosonography is a high-resolution imaging of the pancreas enabling the detection of small lesions (e.g. endocrine tumors). Endoscopic ultrasonography is furthermore the most reliable method for local staging of pancreatic and ampullary carcinoma. The role of endosonography in benign gastroenterological disorders is less well established. With the increasing use of laparoscopic surgery endosonography may become even more important in the future. PMID- 1509788 TI - [Endoscopic sonography of the anorectum in inflammatory rectal diseases]. AB - 213 patients, classified in 3 groups, were examined in a prospective trial using endorectal ultrasound. 80 patients (group A) had no anorectal disease, the endorectal ultrasound showed normal structures of the anorectum and the perirectal tissue. 80 patients (group B) suffered from Crohn's disease, 30 of them had no clinical signs, the rest of this group (50 patients) felt pain in the anal/perianal region. 83 patients (group C) had perianal abscesses or fistulas, Crohn's disease could be excluded. In all 64 perianal fistulas and 66 perianal abscesses were diagnosed. The results of the rectal-proctological examination were compared with endorectal ultrasound. 100% of the perianal abscesses could be recognized using endosonography. The digital-proctological examination revealed only 57% of perianal abscesses and 48% of perianal fistulas; the supralevatory abscesses couldn't be detected proctologically at all. By endorectal ultrasonography we obtained useful informations about localization and extension of the inflammatory process. From a therapeutic and prognostic view the endorectal ultrasound is a simple, practicable and useful method to investigate perianal and anorectal diseases. PMID- 1509789 TI - [Intestinal regulation of pancreatic enzyme secretion: stimulatory and inhibitory mechanisms]. AB - How exocrine pancreatic secretion is regulated is only partly known. It is assumed that interaction of several neural and hormonal mechanisms is involved. In man, the intestinal component of these control mechanisms is very important while extra-intestinal mechanisms (such as the cephalic and the gastric phase) play lesser roles. Regulation of pancreatic secretion by the intestine is composed of three main mechanisms. 1. The proximal intestinal (duodenal) phase of the secretory response to a meal is elicited by nutrients within the proximal intestinal lumen. It is mediated mainly by interactions between cholinergic reflexes and release of the peptide hormone cholecystokinin (CCK). Recent data suggest that part of the action of CCK is not exerted directly on the acinar cellular level, but rather by modulation of cholinergic inputs. 2. The distal intestinal (ileal) phase is elicited by contact of the distal intestinal mucosa with nutrients that pass through the ileal lumen due to physiological malabsorption. The ileum (in contrast to the duodenum) induces net-inhibition of pancreatic secretion. The mediation is unknown, candidate mediators are PYY and GLP-1. 3. Intestinal feedback-regulation of pancreatic secretion in humans is controlled by intraluminal protease activity; this mechanism is not covered in the present paper. PMID- 1509790 TI - [Two aspects of the contribution by Stolte et al., "Omeprazole-induced pseudohypertrophy of parietal cells", provide reason to comment]. PMID- 1509791 TI - [Using endoscopy in peptic lesions of stomach and duodenum]. PMID- 1509792 TI - [Cholesterol lowering and life expectancy: a critical evaluation]. AB - Numerous studies have confirmed a positive correlation between serum cholesterol levels and the occurrence of coronary artery disease. Lowering cholesterol by 1% is accompanied by a reduction of coronary events by 2%. The rate of fatal coronary events is not significantly influenced. Coronary angiography demonstrated only a mild average reduction of coronary lesions after cholesterol lowering therapy. This might be explained by the low lipid content of a coronary plaque (5-15%). The majority of intervention trials revealed an increase of the extracardiac mortality in treatment groups. Thus, up to the present, it remains unproven that cholesterol-lowering therapy leads to an increase in life expectancy. PMID- 1509793 TI - [Relationship between lipid metabolism disorders and age of first manifestations of coronary heart disease]. AB - In 509 male patients, age less than 45 years, with angiographically documented coronary artery disease (CHD) we found (in contrast to age-matched controls: 459 participants of the PROCAM study) an increased amount of total cholesterol (259 vs. 221 mg/dl), LDL-cholesterol (185 vs. 142 mg/dl), Apo-B (138 vs. 118 mg/dl), lipoprotein(a) (12 vs. 5 mg/dl) and uric acid (6.4 vs. 5.8 mg/dl); HDL cholesterol (40.5 vs. 46.8 mg/dl), Apo-A-I (122 vs. 143 mg/dl) and Apo-A-II (38 vs. 43 mg/dl) were significantly lower. These differences in lipid-metabolism between CHD-patients and controls in the younger group were essentially more pronounced than in older individuals of a group of 423 male patients over the age of 45 years who suffered from CHD and 545 age-matched PRO-CAM participants. Among the extent of the disorder in lipid metabolism, the apolipoprotein E polymorphism, and the age of onset of CHD there exists a significant correlation which proves the special importance to therapeutically influence disorders of lipid metabolism especially in younger patients. PMID- 1509794 TI - [Modulation of vascular tone of normal and arteriosclerotic arteries by leukocytes]. AB - Leukocytes, in particular mononuclear cells, play a central role in the pathogenesis of arteriosclerosis. The arteriosclerotic vessel wall is chemotactic for circulating leukocytes. Activated leukocytes are known to release a variety of vasoactive substances. Thus, activation of leukocytes in diseased arteries is not only an epiphenomenon of an inflammatory process, but instead may contribute to arteriosclerosis-associated complications such as vasoconstriction/vasospasm and thrombotic vessel occlusion. Influence of leukocytes on vascular tone appears to be complex and may be modulated by the presence of intact endothelium and additional blood constituents such as platelets. In vitro, mononuclear and polymorphonuclear leukocytes both relax and contract isolated arteries according to experimental conditions and leukocyte isolation protocols. In vivo, activation of leukocytes by chemotactic peptides f-met-leu-phe or complement C5a produces pronounced vasoconstriction. Mediators of these leukocyte-induced vascular responses are partially characterized and consist of nitric oxide (or EDRF-like factor), superoxide anions, thromboxane A2, peptidoleukotrienes, and an unknown contractile factor. In addition, leukocytes may indirectly modulate vascular tone by cleavage of angiotensin II from angiotensinogen or angiotensin I, and by inhibiting or stimulating platelet aggregation. Thus, leukocytes and their products may have several pathways to modulate vascular tone. Abnormal interactions between endothelium-platelet-leukocytes with vascular tone may play an important role in the pathogenesis of vascular complications in patients with coronary artery disease. PMID- 1509795 TI - [Anti-arrhythmia and pro-arrhythmia effects of oral cibenzoline therapy in sustained ventricular tachycardia]. AB - The efficacy and safety of the new class-I antiarrhythmic drug cibenzoline was assessed in 12 patients with spontaneous and inducible ventricular tachycardia. Programmed ventricular stimulation, 24-h ambulatory electrocardiogram (ECG), and continuous ECG monitoring were performed without antiarrhythmic drugs and after oral administration of 254 +/- 80 mg of the substance. Oral cibenzoline suppressed the induction of tachycardia in only one patient. Induction of tachycardia was more difficult in two patients, unchanged in four patients, and easier in two patients. Cycle length of induced tachycardia and QT-interval corrected for frequency were not changed significantly; effective refractory period of the right ventricle was prolonged. Twenty-four hours of ambulatory monitoring during cibenzoline treatment (n = 9) showed no significant increase in the frequency of ventricular premature complexes. However, spontaneous sustained ventricular tachycardia developed in three patients after initiation of cibenzoline treatment. In two patients, termination of induced ventricular tachycardia was significantly more difficult under cibenzoline; several DC-shocks were required to terminate the tachycardia. Thus, the use of oral cibenzoline in patients with sustained spontaneous and inducible ventricular tachycardias showed a low antiarrhythmic efficacy at programmed stimulation and a high incidence of spontaneous ventricular tachycardia. PMID- 1509796 TI - [Value of a provocation test with diprafenone in patients with bifascicular block]. AB - The significance of provocative tests in patients with bifascicular block is not established. We studied 14 patients with bifascicular block, syncope and documented episodes of high degree AV-block. 1.5 mg/kg Diprafenon was given after a period of at last 12 hours 1:1 AV-conduction. Electrophysiologic evaluation was performed before and after diprafenon. AV-block III could be provoked in 1 of 14 patients with Diprafenon. Therefore a total AV block occurred in 7% of patients. The low sensitivity of provocative test with Diprafenon even in patients with documented high degree AV-block prevents its application in clinical practice. PMID- 1509797 TI - [Left ventricular catheter ablation of the AV conduction system with radiofrequency electric current]. AB - We report on a 32-year-old female patient with a history of recurrent atrial fibrillation and rapid ventricular response (up to 240 beats/min) resistant to multiple drug therapy. In this patient, we successfully performed a radiofrequency catheter ablation of the atrioventricular (AV) junction from the left ventricle, after radiofrequency energy application in His-position above the tricuspid valve was unsuccessful. This technique offers an-alternative treatment in patients in whom the conventional right-sided catheter ablation of the AV junction proves ineffective. PMID- 1509798 TI - [Effects of endurance training on left ventricular filling dynamics: a study using stress Doppler echocardiography]. AB - To evaluate the impact of endurance training on left-ventricular (LV) filling dynamics Doppler mitral flow was derived in 23 amateur endurance-trained athletes (AT) aged 31 (24-39) years with a personal marathon record greater than or equal to 200 min, and in 20 ultra-endurance athletes (UEA) aged 38 (28-42) years with a personal marathon record less than 200 min during bicycle exercise in supine position. Twenty-two untrained healthy volunteers (UT) aged 27 (24-30) years served as control. In particular, atrial filling fraction (AFF) as the relative share of atrial contribution to LV filling was measured. At rest AFF was significantly higher in UT (29%) as compared to AT (25%) and UEA (25%). During exercise (150 watt) atrial fraction increased significantly more in UT (37%) as compared to AT (34%) and UEA (29%) (p less than 0.01). At this point of measurement UEA had significantly lower values for AFF than AT (p less than 0.001). Two min post exercise atrial filling fraction already reached baseline values in UEA (24%) and AT (26%), while it remained significantly elevated in UT as compared to baseline values (38%, p less than 0.001). Ten min post exercise atrial filling fraction showed still elevated values in UT (32%), but decreased under baseline values in UEA (23%). No differences in heart rate between the two athlete groups at all times of measurement were observed. Thus, while atrial filling fraction rose in all study groups during exercise, it returned earlier to baseline values in athletes than in untrained subjects. This indicates a better cardiac adaptation to physical stress and a better diastolic performance during exercise in endurance-trained athletes, being even more pronounced in ultra endurance athletes. PMID- 1509799 TI - [Economic aspects of financial security for the elderly]. PMID- 1509800 TI - [The quality of life of the elderly in Germany]. AB - The quality of life of the elderly in Germany is described in respect to selected aspects of objective living conditions and subjectively perceived quality of life. On the background of a general trend to an "aging society" a new situation has arisen for the elderly in unified Germany. The analyses depend on representative data from official statistics and the social sciences and they are concerned with demographic characteristics, distribution of wealth, and indicators of well-being. The conclusion is that, on the whole, the elderly cannot be regarded as a social problem; moreover, the challenge is to correct social inequality among the elderly people. PMID- 1509801 TI - [The development of needs and income security in the elderly--some general comments]. AB - The development of the requirement of private persons (by households) is discussed by micro-economic models, legal regulations, and cross-section-data, and is represented in stylized figures. These hypothetical longitudinal profiles are compared to those of income. The analysis supplies evidence of increasing requirement and decreasing income during retirement. PMID- 1509802 TI - [Monetary security for the aged--concepts of political distribution goals and income-related effects of pension security systems]. AB - This contribution discusses some theoretical aspects related to the question of whether, and in what way, a uniform social security target has been defined for the monetary old-age protection in the Federal Republic of Germany, and to what extent different pension schemes fulfill this target. The analysis leads to the conclusion that only a "target range", and not a defined value, has been developed for the indicator "individual replacement rate". The investigation into the effects of old-age pension schemes on income shows that, even after benefit cuts, public sector employees, on the whole, are better protected than employees in the private sector. A future, detailed empirical analysis would have to investigate individual social groups. PMID- 1509803 TI - [From foreign worker to pensioner--selected aspects of financial security and social care of elderly foreigners in Germany]. AB - There is evidence that many older migrants of foreign nationality remain permanently in the Federal Republic of Germany. Therefore the question of their social protection after retirement arises. This contribution discusses the financial protection via statutory pensions and social assistance, as well as the care provided by their families or on an inpatient or outpatient basis. Deficits in social protection of older immigrants are evident, which should be investigated more thoroughly and dealt with by social policy. PMID- 1509804 TI - [Effect of phases of unemployment on amount of pension--a micro-economic long term analysis]. AB - "What effect has the latest German pension reform on the future pension payments of individuals who experienced unemployment during their working life?" is the main question raised by this article. Model calculations show an income reduction of just over 2%, assuming 3 years of unemployment and 4 years of uninsured interruption caused by other factors. There by, the pension is certainly not in jeopardy. A comparison of different legal regulations of the past 3 decades shows, however, that the latest reform leads to the most substantial reductions. PMID- 1509805 TI - [Effects of the survivor and dependent children law on social security of widows and widowers and distribution of pensions]. AB - The article takes up the discussion about the individual social security of spouses in Germany and describes some effects of German legislation which went into effect in 1986 and regulates the social security of surviving dependents and requires declaration of child-care provision by pensioners (the so-called "Hinterbliebenen- und Erziehungszeitengesetz"). The primary question is, what effect the most current family income has on the individual replacement rate for widows and widowers. What additional information is needed to record the distributional effects of the act is also discussed. PMID- 1509806 TI - [Minimal monetary insurance for the elderly--systematic overview of current regulations and recommendations for an alternative model]. AB - This contribution adds to the intensive discussion about a suitable reform of the German old-age security system with regard to the aim of poverty avoidance. Starting from a multitude of existing and alternatively proposed models, basic forms of a minimum-income protection for the elderly are distinguished by select criteria. The resulting systematic survey is intended as a basis for comparative analyses of economic effects. The results could substantially support the necessary political decision-making process. PMID- 1509807 TI - Benign breast disease in Papua New Guinea. AB - In this study 302 biopsy-confirmed benign breast lesions in Papua New Guinean (Melanesian) women during a ten-year period were reviewed. Inflammatory breast disease was the most frequent type. Chronic mastitis, chronic suppurative mastitis and abscesses formed 32% of benign breast lesions and 71% of the group of mastitides. 10 cases of tuberculous mastitis were recorded. Fibrocystic disease was observed at a lower age (31.9 +/- 8.2 years) than has been reported from Black United States and West Indian populations. The high frequency of mastitis is an important finding. This is most likely to be associated with lactation. Proper hygiene during breastfeeding and the judicious use of antibiotics should reduce this high frequency. Education of women about these matters should form part of health education programs in Papua New Guinea. PMID- 1509808 TI - Obstetrics and childbirth at the Aitape Health Centre, Papua New Guinea. AB - Routinely collected obstetric data at the Aitape Health Centre, Papua New Guinea over the years 1986, 1988 and 1989 were analyzed and compared with figures from western New Guinea of about thirty years ago and with those of rural African hospitals. Data from 924 deliveries were analyzed. 30% were born before arrival (BBA). The number of abnormal deliveries was high. This was in part due to the high frequency of twin births (4.5%). Among the BBAs puerperal sepsis and stillbirth were significantly higher than among those who delivered in the health centre. The stillbirth frequency was 3.4%. The sex ratio male:female at birth was 120.9. The large number of retained placentae with manual removal (5.2%) was related to high parity; 33.5% of the women delivering at the health centre were para-4 or more. 20% of male and 24% of female newborns had low birthweight (less than 2500g). PMID- 1509809 TI - The development of rural laboratory services in Papua New Guinea. AB - The health service of Papua New Guinea is targeted at village level primary health care, through aid posts and health centres. There is an increasing demand for providing these facilities with basic diagnostic laboratory services at the health centre level. To accomplish this, an inservice training program has been established to train existing health workers in specific laboratory skills. A management support scheme has also been instigated to ensure that the most effective use is made of these laboratory-trained staff. This has created a team of rural laboratory workers to support the clinical management of patients in rural locations throughout Papua New Guinea. PMID- 1509810 TI - A quality assurance for rural laboratories: a report on a trial distribution in Momase Region, Papua New Guinea. AB - The strengthening of laboratory services in rural health centres is an important component of the Papua New Guinea National Health Plan. As part of the management support scheme for these services a National Quality Assurance Scheme has been formulated to monitor their technical performance. A trial distribution of quality assurance specimens to 44 laboratories in the Momase Region was met with enthusiastic response and encouraging results. The trial will be used as a model for a nation-wide distribution. PMID- 1509811 TI - Scuba tanks as a compressed air source in positive-pressure ventilation. AB - Throughout the developing world there is a general problem of ensuring regular deliveries of medical supplies to hospitals. This includes the supply of compressed gases. At one regional hospital in Vanuatu, we were faced with the problem of how to provide economically a source of compressed gas at regulated pressure to drive an anaesthetic ventilator. We eventually adapted the output from a Scuba cylinder for this purpose. This paper describes the simple modifications necessary and suggests other uses for this source of compressed air that could be implemented in hospitals with small to medium case loads and access to a diving compressor. PMID- 1509812 TI - Prevalence of anaemia and iron deficiency at different levels of urbanization in Vanuatu. AB - Mean haemoglobin and plasma iron levels and prevalences of anaemia and iron deficiency were determined in three population samples of Vanuatuans aged 20 or more years as part of a noncommunicable diseases survey in 1985. The three samples were drawn from separate urban, semirural and rural populations. Age adjusted mean haemoglobin levels were highest in the urban sample and lowest in the rural sample, and plasma iron levels were highest in the urban sample and lowest in the semirural sample. Mean values in each location were generally higher in male subjects than in nonpregnant female subjects. The overall prevalence of anaemia was 10.1% in nonpregnant female subjects and 5.3% in male subjects by World Health Organization (WHO) definitions. These prevalences are lower than those reported for most other developing countries, including some Pacific island nations. Iron deficiency was more prevalent in females than in males (females 17.2%; males 5.0%). Approximately 40% of anaemic subjects were also iron deficient, and there was a significant positive correlation of plasma iron levels with haemoglobin concentration. This suggests that haemoglobinopathies may not be a major cause of anaemia as previously reported. Although most anaemic subjects (88%) had only mild anaemia, in view of the physical lifestyle of rural and semirural Vanuatuans it would be important to optimize haemoglobin levels in these populations. PMID- 1509813 TI - Skin infections in Tanna, Vanuatu in 1989. AB - Skin infections are an important health problem in Vanuatu and other Pacific island countries. In this study, 18,223 people, representing 90% of the population of the southern island of Tanna in Vanuatu, were examined. Scabies was found in 16% of those screened, with 24% of children under 10 years affected. Other skin infections were predominantly furuncles, abscesses, impetigo and cellulitis and were found in 12% overall and in 16% of children under 10 years of age. These infections were found to be more common in larger households and in the vicinity of the volcano Yasur. Strategies for prevention and management of skin infections in Vanuatu are discussed. PMID- 1509815 TI - Maternal survival and village delivery. PMID- 1509814 TI - Convulsions in children. PMID- 1509816 TI - Age at menarche and associated nutritional status variables in Karimui and Daribi census divisions of Simbu Province. AB - Age at menarche was estimated from data on 310 girls and young women living in Karimui and Daribi census divisions of Simbu Province in 1987. The area has high malnutrition rates among children under five years of age and short adult female stature suggesting that onset of menses should be late. However, other work has shown young ages at the birth of first children and high overall fertility rates among women. The prediction of age at menarche from adult female height is not valid for this population; the actual age at which 50% of girls had commenced menstruating is approximately one and a half years earlier, at 15.8 years, than the predicted age. The nutritional status variables investigated and found to be associated with the age at menarche are height, weight and triceps skinfold thickness. At any given age girls whose nutritional status was better, particularly in terms of weight, were more likely to have commenced menstruation. Menarche appears to be followed closely by onset of reproductive function, with the age at the birth of first children estimated at 17.2 years. A consequence of early entry into reproduction, particularly for girls in areas where undernutrition is common, is a period of considerable nutritional stress during adolescence. Intervention programs should consider this and target these groups for additional health, family planning and nutritional advice. PMID- 1509817 TI - Compliance profiles of paediatric patients in an outpatient department. AB - A cross-sectional study was carried out in paediatric patients with acute illnesses attending an outpatient clinic at Angau Memorial Hospital, Lae. The aim of the study was to estimate the level of compliance to previously prescribed medication. 45 sick children were included in this study. Their parents or guardians were interviewed and their health record books carefully examined for details of prescribed and administered medication. Poor compliance to prescribed medication was observed in 38% of cases. A number of reasons for the poor compliance were documented. In a second, closely related study designed to determine the reliability of oral medicine ingestion, 348 children were enlisted. In 7% of them oral medicine ingestion was not satisfactory. These results emphasize the need to carefully consider each sick child individually, especially with regard to optimizing compliance, whenever drugs are prescribed. PMID- 1509818 TI - [Stability of shy-anxious-inhibited behavior in kindergarten children]. AB - The stability of internalizing disorders was studied over a period of 15 months in a sample of three- to five-year-old children attending preschool (N = 280). Stability coefficients for shyness/inhibition (rT1-T2 = .65/.77), oversensitivity (rT1-T2 = .49/.69) and dependency (rT1-T2 = .43/.64) showed a high to moderate (normative) continuity during this stage of development. There were no sex differences but there were significant age variations: The stability of shyness/inhibition was about twice as high in the oldest cohort as in the youngest age group. Persistence of internalizing behavior dimensions was much stronger in a withdrawn-aggressive group than in a withdrawn-nonaggressive group. Peer status had some predictive utility, but for the sample as a whole there was only a low correlation between sociometric variables (T1) and internalizing scores (T2); the level of correlation was strongly dependent on the children's age and sex. PMID- 1509819 TI - [Clinical and cytogenetic problems in diagnosis of fragile X syndrome]. AB - The fragile X or Martin-Bell syndrome is the second most common chromosomal cause of mental retardation. It has a prevalence of 1:1000; the clinical and psychopathologic symptoms vary. The difficult diagnosis rests on cytogenetic evidence of the fragile site at Xq 27.3. 18 patients were tested for fragile X syndrome in 4 different laboratories. Of the 32 chromosomal analyses performed 17 were positive and 15 negative. In 11 patients 2 or more analyses were performed in different laboratories for verification. In all 11 cases the findings were discrepant and therefore the initial findings were considered false positive. The clinical and cytogenetic problems are discussed and diagnostic guidelines summarized. PMID- 1509820 TI - [Periodic psychosis in adolescence]. AB - In view of the fact that in the early part of this century Emil Kraepelin clearly described the relationship between psychotic episodes and the menstrual cycle it is surprising that the scientific elucidation of the phenomenon as a primary endocrine disorder came only decades later. Furthermore, the German literature has paid little attention to the problem, which was given the name "periodic psychosis of puberty" in 1963. In this article an overview of the literature is given, the symptoms and course of the disorder are described and two cases are reported. The course appears to be variable. There can be spontaneous remission after a variable length of time but also a transition into other forms of psychosis. The treatment is pharmacological. PMID- 1509821 TI - [Child psychiatry and child neurology]. PMID- 1509822 TI - [The effect of life change events on cognitive and socio-emotional development in early childhood]. AB - The present study investigates the role of life events of differing durations in the cognitive and social-emotional development of infants. A total of 354 children were examined at the ages of 3 and 24 months and the children's parents were interviewed about the occurrence of live events in this interval. The total number of life events was a significant predictor of changes in the level of cognitive and social-emotional functioning. Changes in the caregiver and marital discord were the best predictors of a child's social-emotional development, and serious illness in the child and changes in the caregiver were the best predictors of a child's cognitive development. PMID- 1509823 TI - [Adaptation of the Kaufman Assessment Battery for Children for German- speaking areas. Part 1: Introduction of the battery]. AB - The German version of the K-ABC is an adaptation of Alan and Nadeen Kaufman's test, published in the USA in 1983. The battery comprises a total of 16 subtests, organized in different scales, for the assessment of mental processing and achievement in children in the age range of 2-6 to 12-5 years. The underlying theory of intelligence measurement is based on findings in the fields of cognitive psychology and neuropsychology. It differentiates from sequential simultaneous information processing. The present article provides information about adaptation and structure of the German version, and about the standardization performed with a sample of 3098 children. Part 2 of this article, to appear soon, will survey application of the test battery, diagnostic relevance, and reliability and validity scores. PMID- 1509824 TI - [Specific developmental disorders and the family--pathogenetic factors in children with behavioral disorders]. AB - 121 children aged 5;6 to 8;6 years referred to our center as out-patients because of various types of behavioral problems and showing distinct symptoms of minor neurological dysfunction were investigated with regard to family-related variables, specific developmental disorders, and the extent of the behavioral problems. A comparison of the groups with few and numerous behavioral problems showed a significant difference in the number of familial risk factors, but not in the degree of neurological and cognitive dysfunction. These results indicate the importance of child-independent familial factors, e.g. marital problems and psychosocial stress, in the pathogenesis of behavioral disturbances in children with minor neurological dysfunction. The resulting need for a family-oriented perspective in assessment and therapy is discussed. PMID- 1509825 TI - Comparison of two media for the isolation of thermophilic Campylobacters from waste waters of different quality. AB - Counts of thermophilic campylobacters from 31 different waste water samples were parallel estimated with two different cultivation media. The resulting increased isolation sale obtained with an modified Charcoal-Cefoperazone-Deoxycholat-Medium (MCCD-Medium), was statistically significant. An 15.8 fold increased isolation rate, compared with the standard medium, could be estimated with the help of the geometric mean. PMID- 1509826 TI - [The occurrence of Campylobacter in a mountain brook]. AB - The mountain river showed fecal water pollution at all sample sites studied. The arithmetic mean values of total coliforms ranged between 28 and 196/ml. Campylobacters were isolated from all sample sites studied, with a maximum value of 1,100 Campylobacter/100 ml river water. The MCCD-medium resulted in significantly higher isolation rates of Campylobacter from water samples than the VTPRC-medium compared. Colony counts, total coliforms and Campylobacter showed numerical relations of 3831:100:1 respectively. PMID- 1509827 TI - Microbiological research on soft drinks: discolouring of natural-flavoured products. AB - The results of experiments testing the effects of yeasts, sunlight, and temperature on the food dyes tartrazine, ponceau 4R, indigotin and azorubin (used for colouring ginger soft drink) are reported. Light was found to exert a greater influence than heat, and yeasts growth hastened colour degradation. Yeasts assimilated to varying extent the colouring compounds and, when failing to do it, showed a certain power of adsorption by the no longer viable cells. PMID- 1509828 TI - Enzymatic production of alpha-aminoadipate-delta-semialdehyde and related compounds by lysine epsilon-dehydrogenase from Candida albicans. AB - L-Lysine epsilon-dehydrogenase [L-lysine:NADP+ oxidoreductase (epsilon deaminating), EC 1.4.1.15] of Candida albicans was studied emphasizing its application for the production of alpha-aminoadipate-delta-semialdehyde and related compounds. A high enzyme level (240 pkat/mg of protein in the crude extract) could be attained during growth in the presence of L-lysine as sole nitrogen source. After optimization of the reaction conditions a partial purified enzyme (1.5 nkat/mg of protein) was used to produce alpha-aminoadipate-delta semialdehyde, S-(beta-acetaldehyde)-cysteine, alpha-amino-delta-hydroxyadipate semialdehyde and alpha-amino-gamma-hydroxyadipate-semialdehyde from the corresponding substrates lysine, S-(beta-aminoethyl)-cysteine, 5-hydroxylysine and 4-hydroxylysine, respectively. After purification of the compounds using Dowex 50 x 4 chromatography a yield of the products between 4.6 and 6.8% was achieved. PMID- 1509829 TI - Antibacterial activity of N-[2-(dodecanoylmethylamine)ethyl]-alkyl dimethylammonium bromides. AB - The study contains the results of determination of antibacterial activity of the newly synthesized series of N-[2-(dodecanoylmethylamine)ethyl] alkyldimethylammonium bromides. The efficiency of the compounds has been characterized towards three species of the genus Clostridium such as Clostridium perfringens, type A, Clostridium bifermentans, Clostridium sporogenes and one strain of the genus Lactobacillus such as Lactobacillus yamanashiensis. The antibacterial activity of the studied compounds has been tested in different time intervals. Out of seven investigated compounds, four compounds exerted the pronounced antibacterial activity on Clostridia (CMIC equals to 0.0039-0.0078 mmol/litre) and three compounds influenced the growth of Lactobacillus yamanashiensis (MIC equals to 0.004-0.006 mmol/litre). The most effective compound was found to be n-octyl derivative. These compounds were more effective towards the tested Clostridia strains than the comparing standard disinfectant such as Ajatin. PMID- 1509830 TI - Production of ochratoxins by some Egyptian Aspergillus strains. AB - In all the investigated Aspergillus ochraceus and A. alliaceus strains the maximum quantities of ochratoxins produced on yeast extract-sucrose (YES) medium exceeded that detected on wheat solid medium except A. ochraceus 67. The shake cultures lowered ochratoxins formation. The maximum yields of ochratoxins did not coincide with maximum fungal growth. In most A. strains investigated, the total ochratoxin contents of the culture filtrates highly exceeded that of the mycelia. PMID- 1509831 TI - [Osteoporosis from the gynecologic viewpoint]. AB - Osteoporosis is a disease of the elderly characterized by a loss of bone mass causing fractures in presence of an inadequate trauma. Osteoporosis has to be considered as a significant ailment in our population. This review outlines epidemiology, pathogenesis and risk factors of primary osteoporosis. The physiological role of sex hormones, especially of estradiol, for the development and maintenance of skeletal bone mass is explained. Principles of preventive estrogen(-progesterone) application for the prophylaxis of postmenopausal osteoporosis are specified by several estrogen replacement studies in postmenopausal women. Individual replacement therapy for the compensation of a long-lasting estrogen deficit in the reproductive age group, in pre- and postmenopausal women is the assignment of the gynecologist in order to protect the skeletal system. PMID- 1509832 TI - [Shoulder dystocia--a rare obstetrical complication]. AB - Shoulder dystocia is an uncommon complication of delivery with a high neonatal morbidity rate. This review describes the use of the most important shoulder dystocia maneuvers and underlines the demand to perform a written description of all details of the management during delivery. PMID- 1509833 TI - [Evaluation of the pulsatile curve of the placental blood flow profile by polynomial analysis]. AB - The analysis of uterine and umbilical blood flow velocities using A/B ratio, resistance index and pulsatility index has shown to be a highly specific and sufficiently sensitive method in the evaluation of high risk pregnancies. In situations of high peripheral vascular resistance diastolic velocities are low and index values are high. Additional information of flow velocities curves, as diastolic notching, is not represented in the indices commonly used. A mathematical model was established using polynom analysis of blood flow velocity curves. In a group of 78 patients with intrauterine growth retardation polynome analysis of uteroplacental flow velocity curves was more sensitive than resistance index and pulsatility index. PMID- 1509835 TI - [New perspectives of in vitro kallikrein treatment. II. Study of the hamster ovum penetration test in relation to the kallikrein-kinin system]. AB - A significant enhancement of the fertilizing capacity of human spermatozoa by Kallikrein has recently been described in a former study. To assess the therapeutic possibilities it would be of great interest to know more about the biochemical effect of Kallikrein on the fertilizing capacity of human spermatozoa. This fact made the authors investigate 64 semen samples in which the binding score and the fertilizing capacity were determined after application of Kallikrein in a HOP-test (hamsterovum-penetration-test) and compared to the control. Furthermore these results were compared to the varying concentrations of the components of the Kallikrein-Kinin-system. An application of Kallikrein in the swim-up preparation resulted in a higher motility in patients with asthenozoospermia, whereas the patients belonging to the group of oligoasthenozoospermia showed a lower progressive motility compared to the control. The binding score (number of affixed spermatozoa) showed nearly the results in both preparations. On the other hand the fertilizing capacity in the Kallikrein preparation was significantly higher. A possible connection with the concentrations of the components of seminal plasma has not been found, yet, but regarding all results a direct enzymatic effect of Kallikrein on fertilizing potential can be assumed. PMID- 1509834 TI - [Clinical experiences with treatment of granulosa cell tumors]. AB - Symptoms, tumor morphology and clinical course were reviewed in 15 cases of granulosa cell tumors of the ovaries. The main symptoms were irregular menstrual bleedings. In 2 cases were found signs of glandular cystic hyperplasia additionally and in one case an adenocarcinoma of the endometrium. The appropriate treatment was the hysterectomy with bilateral salpingo-oophorectomy performed in most of the cases, followed by additional irradiation and polychemotherapy in 4 cases each. PMID- 1509836 TI - [The prognostic value of the postcoital and post-insemination test]. AB - Artificial inseminations with the semen of the husband (pre- and intracervical, intrauterine AIH) were carried out on 201 infertile women. Even though 41 women conceived on insemination, 16 of these and 38 of the unsuccessfully treated women actually became later pregnant without medical aid. An attempt to judge the eventual chances of success of AIH from the results of the PCT and PIT failed, as there was no correlation between the number and percentage of motile spermatozoa in cervical mucus post coitum and post inseminationem and the number of pregnancies. There was no clinical correlate for the differences observed between the results of the PCT and PIT. PMID- 1509837 TI - [Rare metastasis of vulvar cancers]. AB - A report is given on two rare cases of metastases of a primary vulvar carcinoma. One patient got metastases in the uterine cervix and axilla, the other had a local destructive process in the mandibula. PMID- 1509838 TI - [Cardiotocography practice 22]. PMID- 1509839 TI - [Plasmid composition of Yersinia pestis strains from different natural foci]. AB - The study of the plasmid composition of 246 Y. pestis strains from different natural foci in the USSR and other countries revealed that 173 strains (70%) carried three known plasmids with a molecular weight of about 6, 45-50 and 60 megadaltons (MD) respectively. In 20 strains (8%) obtained from different sources additional cryptic plasmids were detected. In some cases the absence of one or two typical plasmids was observed. Replicon pPst was shown to have quite constant molecular weight (6 MD), whereas plasmids pCad and especially pFra exhibited certain variations of their molecular weight (45-49 MD and 60-149 MD respectively) in strains of different origin. PMID- 1509840 TI - [The LPS-protein complex from the outer membrane of Francisella tularensis]. AB - LPS-protein complex containing proteins of 15 kD, 17 kD and 19 kD was isolated from F. tularensis outer membrane by solving with sodium deoxycholate with the subsequent gel filtration on Sephacryl S-200. Protein of 17 kD constituted the main protein component of the complex. The LPS-protein ratio of this complex was 1:1. Proteins contained in LPS-protein complex have mainly the alpha-spiral structure. In the absence of detergent these proteins and LPS formed micelles with molecular weight exceeding 10(7) D. LPS-protein complex was shown to have a protective effect in mice infected with F. tularensis virulent strain 503. PMID- 1509841 TI - [Biological characteristics of strains of lactobacilli, promising for use as eubiotics]. AB - In the course of in vitro studies 3 Lactobacillus strains with pronounced antagonistic activity against some pathogenic and opportunistic bacteria (shigellae, enteropathogenic Escherichia, Proteus, staphylococci) were selected. In experiments on germ-free rats faint colonization by L. plantarum 37 was observed in the small intestine, as well as in the large intestine when low doses of these bacilli were introduced into the gastrointestinal tract of the animals. In vitro experiments demonstrated the decreased growth rate of this strain. The prophylactic administration of two eubiotic strains, L. plantarum 37 and L. fermentum 39, simultaneously with chloramphenicol to primates inhibited the growth of opportunistic bacteria, though L. fermentum 39 excessively suppressed the content of Escherichia coli in the enterobacterial population. The optimum biological effect was achieved with the therapeutic use of these three strains for the correction of dysbiotic disturbances caused by the administration of tetracycline in volunteers. PMID- 1509842 TI - [Intestinal microflora in young children with rotavirus infection]. AB - A total of 270 children with rotavirus diarrhea were examined. The quantitative and qualitative composition of their intestinal microflora was studied. Most frequently microorganisms of the genus Enterobacter and most seldom, Serratia were isolated. A decrease in the amount of bifidobacteria, normal Escherichia coli and an increase in the amount of lactose-negative Escherichia were noted. In cases of pronounced dysbiosis in young children the clinical course of rotavirus infection is aggravated and the period of rotavirus excretion is prolonged. PMID- 1509843 TI - [Studies of AIDS in Lithuania]. AB - The seroepidemiological survey of 400,000 persons aged 20-40 years and belonging to different AIDS risk groups, as well as blood donors, for the presence of antibodies to HIV has been carried out on the territory of Lithuania. This investigation has been made with the use of the assay systems "Antigen", "Peptoscreen" and "Vector" manufactured in the USSR, as well as commercial assay systems from foreign manufacturers, such as Du Pont de Nemours Inc., Organon N. V., Abbott Laboratories, Serodia. The comparison of the results thus obtained has revealed that high frequency of false positive results is characteristic of all assay systems under study, including immunoblotting. These data indicate that test systems based on different acting principles should be used for the detection of anti-HIV antibodies. For the first time a HIV-infected resident of Lithuania has been detected. The investigation carried out in Lithuania has shown that HIV infection is not widely spread in this region, but due to some objective reasons this does not preclude the necessity of the constant epidemiological surveillance of this infection throughout this territory in order to bar the way to this infection. PMID- 1509844 TI - [Epidemiological features of hospital purulent-septic infections in otolaryngological wards]. AB - Prospective epidemiological observation in an otorhinolaryngological hospital has made it possible to distinguish the specific features of pyoseptic nosocomial infections. Such infections, appearing as cross re- and superinfections, are most frequently induced by staphylococci, as well as by Proteus and Pseudomonas aeruginosa. High risk groups include patients with purulent otitis and sinusitis, who have contacted infection through instruments in examination and dressing rooms. The main sources of infection are patients with pyoseptic infections of the ear and sinuses. PMID- 1509845 TI - [Formal methods for epidemiological classification of regions]. PMID- 1509846 TI - [Stability of bacterial aerosols in static conditions]. AB - The influence of acid exopolysaccharides of some Pseudomonas species on the viability and fractional disperse composition of Salmonella marcescens-9 aerosol under static conditions has been studied. Acid exopolysaccharides have been shown to form membranes around bacteria. These membranes, due to their adsorptive and water-retaining properties, seemingly enhance the viability of bacteria in aerosol, both in the process of its generation and during its suspension in the air under static conditions with different values of relative humidity. PMID- 1509847 TI - [Methods used for classification of regions by morbidity]. PMID- 1509848 TI - [Etiological structure of dysentery in the republic of Armenia]. AB - In this work materials on the etiological structure of Shigella infections at different territories of Armenia are presented. Four Shigella species have been found to circulate in Armenia. The dominating etiological agent is S. flexneri with S. sonnei also playing an important role. The serological picture of S. flexneri is characterized by the prevalence of subserovar 2a. PMID- 1509849 TI - [Epidemiological effectiveness of an inactivated three-component flu vaccine with an increased concentration of hemagglutinin in the inoculation dose]. AB - The work presents the results of the evaluation of mass immunization of working adults with inactivated trivalent influenza vaccine under the conditions of an epidemic caused by influenza viruses A (H1N1), A (H3N2) and B. This immunization produced no effect on influenza morbidity in the groups of vaccinees in comparison with those of nonvaccinated persons. The index of effectiveness was 1.0 and less. The ineffectiveness of mass immunization was due to a high level of natural immunity to influenza and the extensive use of influenza vaccine in past years. PMID- 1509850 TI - [The correspondence theory and etiological structure of Shigella infections]. PMID- 1509851 TI - [Effect of regional (wound) revaccination with tetanus anatoxin on the functional activity of immunocompetent cells in the region]. AB - The study made with the use of complex methods established that the local (wound) application of tetanus toxoid rapidly made the manifestation of the lysosomal apparatus more pronounced, increased the oxidizing activity (determined in the nitro blue tetrazolium test) and phagocytic activity of the mononuclear phagocytizing system in the wound and in the regional lymph nodes. The wound application of tetanus toxoid significantly increased blast transformation of T lymphocytes in guinea pigs simultaneously with tetanus wound infection. The study confirmed the pathogenetic expediency of the proposed method for the stimulation of anti-tetanus immunity by the application of tetanus toxoid on the wound which specifically inhibited the primary stage of the infectious process. PMID- 1509852 TI - [Use of highly purified subvirion trivalent flue vaccine ("Grippovak") in groups with a high risk of complications]. AB - During the epidemic season of 1989-1990 the subunit vaccine Grippovac was used in 20 asylums for old people and psychoneurological invalids in Moscow for the protection of the inhabitants and the personnel from influenza. Follow-up of the vaccinees during the period from November 1989 to March 1990 revealed that the use of this vaccine decreased the incidence of influenza-like diseases (ILD) 3.4 4.1 times among the vaccinees in comparison with that in the nonvaccinated control groups and significantly decreased the severity of the course of ILD, as well as the mortality because of ILD, among those vaccinees who had contacted ILD. This is indicative of good prospects of regular vaccinal prophylaxis of influenza at asylums for old people and other persons at a high risk of influenza complications. PMID- 1509853 TI - [Use of commercial highly sensitive tests for detecting HbsAg in healthy persons]. AB - The study has revealed the possibility of the contamination of serum with HBsAg under laboratory conditions during its treatment and preparation for analysis, which may be the cause of false positive results of HBsAg detection by the enzyme immunoassay (EIA). Excluding the factors of contamination, the authors demonstrate the efficacy of commercial systems, such as the passive hemagglutination test system "Gorky" and the EIA systems "Gorky" and "DIAplus", for the detection of HBsAg in the blood of donors in Moscow and Tashkent. PMID- 1509854 TI - [Effect of mytilane, a bioglycan from the mussel Crenomytilus grayanus, on the course and outcome of experimental flu infection]. AB - Materials characterizing the antiviral activity of Mytilane, manifested by the protection of 50-60% of mice infected with the lethal dose of influenza virus and by a decrease in the severity of pathological changes in the lungs of mice, are presented. The inhibiting activity of Mytilane with respect to the reproduction of influenza virus in vivo and in vitro under experimental conditions is demonstrated. PMID- 1509856 TI - [Vaccines in health care in the USSR. General features]. PMID- 1509855 TI - [Effect of immunomodulators of various origin on the histamine-sensitizing activity of whole-cell pertussis vaccine]. AB - Changes in the histamine-sensitizing activity of whole-cell pertussis vaccine (PV) under the action of immunomodulators (IM) of bacterial (peptide and peptidoglycans), synthetic (peptidoglycan) and vegetable origin have been studied. The study has revealed that these IM, introduced orally and parenterally, exhibit histamine-sensitizing activity, depending on the nature of IM and the optimum selection of the doses of IM and PV. PMID- 1509857 TI - [Vaccines in health care in the USSR. General features]. PMID- 1509858 TI - [Interventional endoscopy: what is new?]. AB - New trends in therapeutic endoscopy are presented concerning endoprostheses of the esophagus, endoscopic sclerotherapy of varices and non-variceal bleeding, endoscopic therapy of bile duct stones, palliation of malignant stenoses of the bile duct, endoscopic therapy of acute pancreatitis. Advantages and disadvantages of these new techniques are discussed by analysis of preliminary results and compared with the well established techniques of endoscopy, radiology and surgery. PMID- 1509859 TI - [Therapy of chronic viral hepatitis with recombinant interferon-alpha]. AB - Long term treatment with interferon alpha is the only established therapy for chronic viral hepatitis so far. Depending on the type of viral hepatitis the response rate to interferon alpha is between 15 and 40%. These results can be improved by an appropriate selection of patients and possibly by combination therapy with other immunomodulatory and antiviral substances. The optimal dose in chronic hepatitis B is 5 Mega Units (MU) interferon alpha every other day for 6 months and in hepatitis C 3 MU every other day over 6 months. PMID- 1509860 TI - [Differential diagnosis of fever after returning from the tropics]. AB - Fever is the cardinal symptom of many infections in travellers returning from the tropics and is second in place only to infectious diarrhea. Once the obvious causes of fever in an individual patient have been eliminated, it may be very difficult to find the cause of fever. Fevers can be distinguished by their length of duration and divided into acute fevers i.e. up to 3 weeks duration and chronic fevers i.e. more than 3 weeks duration. Whether fever goes along with leucopenia or a normal white blood cell count on the one hand or with leucocytosis on the other hand is of differential diagnostic value. A schedule based on these two parameters will be presented to simplify differential diagnostic considerations. Two rules of thumb will be stressed: (1) Each febrile illness, even febrile diarrhea, jaundice or meningitis, is to be considered a malaria until it is excluded. (2) Patients returning from tropical areas might suffer from banal infections such as pneumonia, urinary tract infections, cholangitis, etc. as well. PMID- 1509862 TI - Family nursing in a tertiary care setting. PMID- 1509861 TI - [Management of patients with traveler's diarrhea]. AB - Traveler's diarrhea starts 5 to 15 days after arrival with 3 or more watery bowel movements daily in 4 to more than 50% of travelers depending on geographical regions. Enterotoxin producing strains of E. coli are isolated in 20 to 50% of patients, followed by shigella, salmonella, campylobacter and vibrio spp. Rarely giardia lamblia, entamoeba histolytica and cryptosporidia are causative organisms. The cornerstone of treatment is oral rehydration. The efficacy of anti diarrhetics is not convincingly proved and as to loperamid this drug may prolong invasive forms of diarrhea. Antibiotics are indicated if leucocytes or blood are found in stool. Cotrimoxazole and aminopenicillins are loosing efficacy because of growing resistance. The minimal. In a double blind placebo controlled trial with 500 mg ciprofloxacin b.i.d. for 5 days we were able to demonstrate a significant clinical and bacteriologic effect in 132 patients with salmonellosis and campylobacteriosis. PMID- 1509863 TI - Liability protection: The Canadian Nurses Protective Society. PMID- 1509864 TI - Visiting Professor Series at the Royal Alexandra Hospital Department of Nursing. Ethics and accountability. Interview by Doreen Reid. PMID- 1509865 TI - Advanced treatment directives input invited. PMID- 1509866 TI - The caregiver (or nurse) as risk manager: the law and logistics of obtaining valid consents. PMID- 1509867 TI - Breast cancer screening practices of Alberta women. PMID- 1509868 TI - Writing a research grant for AFNR ethical clearance. PMID- 1509870 TI - Nursing education in Australia: recent developments. PMID- 1509869 TI - Pain corner. Humour: an approach to brief episodes of pain. PMID- 1509871 TI - Sound spectrographic studies on the relation between motherese and pleasure vocalization in early infancy. AB - The relationship between the vocalizations of early infants and their mothers was investigated by acoustic analysis. The subjects were eight infants aged 40-70 days and their mothers. The infants were sufficiently developed to utter pleasure vocalization. The acoustic characteristics of the voices of the infants and mothers while communicating with each other analyzed in terms of pitch, duration, latency and melody types. The results were as follows: 1) Correlation was significant between the average fundamental frequencies of the infants' voices and those of their mothers. Motherese and infants' vocalizations were similar in pitch. 2) There was little individual difference in the duration of infants' vocalizations, but a considerable individual difference in the duration of motherese. No correlation was observed in the duration of the vocalizations of the infants and mothers. 3) The latencies of infant vocalization and motherese showed large differences among the infant-mother pairs. There was a tendency for the latency of the motherese to affect the number of utterances by the infant. 4) Significant correlations in the melody types were observed in three mother-infant pairs. These findings indicate that there are significant correlations in the vocal exchanges between infants and their mothers. PMID- 1509872 TI - IgG subclass imbalance in children with acute lymphoblastic leukemia receiving maintenance chemotherapy. AB - Serum levels of IgG subclasses were measured in 18 children with acute lymphoblastic leukemia (ALL) receiving maintenance chemotherapy and in 36 age matched controls in order to attempt to analyse the effects of chemotherapy. The IgG subclasses were measured by enzyme linked immunosorbent assay. Serum IgG1, IgG2 and IgG4 levels in the patients were significantly (p less than 0.01, p less than 0.005, p less than 0.005) lower than in the controls, but serum IgG3 levels in patients were as high as in controls. Suppression on IgG2 and IgG4 were more profound than IgG1. In six children, the levels of the IgG subclasses were measured at diagnosis, during maintenance chemotherapy and one year after cessation of chemotherapy. The levels of the four IgG subclasses at diagnosis and after cessation of chemotherapy were as high as those in control children except for the IgG4 levels in the post-chemotherapy group. IgG2 and IgG4 may be more susceptible to suppression by chemotherapy than IgG1 and IgG3 may not be suppressed by chemotherapy. PMID- 1509873 TI - Growth hormone secretory status in patients with Turner syndrome. AB - The growth hormone (GH) secretory capacities in patients with Turner syndrome aged 5.1-15.9 years and those with constitutional short stature (CSS) aged 5.2 14.2 years were evaluated by pharmacological and physiological means. The GH response to hypoglycemia in the patients with Turner syndrome was lower than that in the patients with CSS. However, the GH response to arginine was not significantly different between the two patient groups. For the physiological test, the integrated concentration of GH (ICGH), the number of episodic peaks and their mean height were evaluated using blood obtained from the patients every 20 minutes for a period of 24 hours. The ICGH and the mean height of the episodic peaks in the patients with Turner syndrome were significantly lower than those in the CSS patients during the night but not during the day. Negative correlation between the bone age and the night-time values of ICGH was observed in the patients with Turner syndrome. Such correlation was not observed in the CSS patients. The patients with CSS showed a significant day-night difference in the ICGH and the mean height of the episodic peaks, but the patients with Turner syndrome did not show any significant day-night difference in either the ICGH or the mean height of episodic peaks. In conclusion, the GH secretory capacity in patients with Turner syndrome is lower than that in CSS patients. PMID- 1509874 TI - Epidemiological studies on measles in Karachi, Pakistan--mothers' knowledge, attitude and beliefs about measles and measles vaccine. AB - In order to gather information on the factors affecting the spread of measles vaccine in Pakistan, 287 mothers living in Karachi were interviewed concerning their knowledge, attitude and beliefs about measles and measles vaccine. Measles had been highly prevalent, mainly among infants between 9 and 18 months of age. The severity of the illness and the frequency of complications were well known and the importance of immunizations was well recognized. In traditional combined families grandparents had made the decision to take children for immunization, but many mothers had begun to feel that they were responsible for participation in the programme. The vaccine acceptance rate had increased sharply in recent years, primarily due to local health educators' activities and mass media such as TV programmes. The present findings confirm the importance of continuous effort toward promotion of primary health care by collaboration of motivated mothers and community health workers. PMID- 1509875 TI - Evaluation of atrial, ventricular and atrioventricular septal defects by cine magnetic resonance imaging. AB - Cine magnetic resonance imaging (MRI) was performed on 20 patients (mean age: 5.3 +/- 4.4 years) with atrial, ventricular, or atrioventricular septal defects for evaluation of cardiac structure and blood flow. Prior to cine MRI, electrocardiographically gated MRI using multislice acquisition was performed on all patients to localize optimal slice location. Cine-MRI was obtained with a 30 degrees flip angle, 15 msec echo time, and 30 msec pulse repetition time, on a 256 x 256 or 128 x 128 acquisition matrix. Abnormalities of cardiac structure were well defined in all patients by gated cardiac imaging. In 18 of the 20 patients, cine-MRI was able to detect shunt flow, visualized as a low intensity signal in comparison with the surrounding blood flow. Cine-MRI can provide not only accurate anatomy of cardiac structures but functional assessment of the cardiac chamber, wall topology and flow relations. Cine-MRI will become an important noninvasive technique for assessment of anatomy and physiology in congenital heart disease. PMID- 1509876 TI - A study of psychosocial factors in the psychosomatic symptoms of adolescents in Okinawa. AB - High school students (N = 902) in Okinawa were asked to participate in a questionnaire survey which was designed to investigate the psychosocial factors in the psychosomatic symptoms of adolescents. The questionnaire focused on mental distress, perception of school and home environment and psychosomatic symptoms. The Japanese Edition Cornell Medical Index-Health Questionnaire (JCMI) for evaluating emotional instability and the New TK Diagnostic Test for Parent-Child Relationship were also utilized. Distress in relationships with family or friends, finding little pleasure in school and/or home, showing emotional instability as diagnosed according to regions III and IV of JCMI, or showing strained parent-child relationships according to the TK Test items were found to be closely associated with psychosomatic symptoms. In addition, students with human relations problems, especially family problems, tended to have a strained relationship with parents and tended to show autonomic hyperactivity represented by orthostatic dysregulation. Students with peer problems tended to have emotional instability and to find little pleasure in school; they had mental as well as urinary and bowel symptoms. The findings of this study suggest that distresses in family or peer relationships, emotional instability and a strained parent-child relationship are important factors in the onset of psychosomatic symptoms in adolescents. PMID- 1509877 TI - The origin of myoclonus and periodic synchronous discharges in subacute sclerosing panencephalitis. AB - We report here a case of a patient with subacute sclerosing panencephalitis (SSPE) and we have analyzed periodic events using dipole tracing methods to clarify the origin of periodic synchronous discharges and myoclonus. Both source generators were located in the subcortical part of the cerebrum, an area adjacent to the thalamus. Although the pathophysiology of periodic events in SSPE has been controversial, dipole tracing methods may contribute to clarify the origin of periodic events in SSPE. PMID- 1509878 TI - Papillary and cystic tumor of the pancreas possibly concealed within a pseudocyst. AB - A 17 year old girl, with a papillary and cystic tumor of the pancreas, probably concealed within a previous post-traumatic pseudocyst of the pancreas is described. At 10 years of age, she had received a drainage procedure for a pancreatic pseudocyst, following a blunt abdominal trauma. The histological examination of the cyst wall did not show an epithelial lining. Seven years after that, she developed anemia and a computer tomography and ultrasonography of abdomen revealed a 10 cm x 9 cm x 8 cm, cystic, multilocular pancreatic mass with solid parts. On operation, a fist-sized, solid and multilocular cystic tumor, located in the body and tail of the pancreas, and infiltrating into the colonic serosa but with no metastasis, was found and completely excised. Histologic and electron microscopic examination revealed the characteristic features of a papillary and cystic tumor of the pancreas. This report suggests that cystic lesions of the pancreas should be carefully checked to decide the best surgical therapy. PMID- 1509879 TI - Hydrops fetalis caused by fetal Kasabach-Merritt syndrome. AB - There have been only 2 previous reports of nonimmunologic hydrops fetalis (NIHF) caused by fetal Kasabach-Merritt syndrome, both of which were pathological studies. This is the first clinical case report of NIHF due to fetal Kasabach Merritt syndrome that was prenatally diagnosed by sonography, computerized tomography, and percutaneous umbilical blood sampling. PMID- 1509880 TI - Clinical experience in using a new type of nasal prong for administration of N CPAP. AB - Nasal continuous positive airway pressure (N-CPAP) has been used in infants with decreased lung compliance for increasing the functional residual capacity (FRC), decreasing the work of breathing and improving the PaO2/PAO2 (arterial-alveolar PO2 ratio) without intubation. However, the currently available nasal prongs for administration of N-CPAP have presented some problems in fixation, and lesions to the nasal septum or nostrils might be induced by aggressive pressure intended to fix them. We would therefore like to report our experience in using a new type of nasal prong for administration of N-CPAP therapy. The nasal prongs we used were provided by Dr. Wung of Columbia University in New York, who first designed them, and have been used safely, effectively and without any complications. PMID- 1509881 TI - Dengue encephalopathy. AB - Dengue encephalopathy or dengue hemorrhagic fever (DHF) with CNS involvement used to be considered a relatively rare condition; but the number of cases reported in human studies has been increasing every year. Diagnosis of dengue encephalopathy is based on clinically diagnosed DHF according to the W.H.O. criteria (1980), with CNS manifestations consisting of abrupt onset of hyperpyrexia, non-transient alteration of consciousness, headache, vomiting--with or without seizures--and normal CSF. Many factors may be considered to be directly or indirectly associated with CNS signs and symptoms in DHF, the main pathology being leakage of plasma into serous spaces and abnormal hemostasis, leading to hypovolemic shock and hemorrhage in many organs of the body. Acute liver failure is considered to be one of the main factors causing brain pathology. One hundred fifty-two cases of dengue encephalopathy admitted during 3 periods at the Cipto Mangunkusumo Hospital in Jakarta were studied retrospectively. The overall incidence was 152 out of 2,441 DHF cases, or 6.2%. The most pronounced symptoms were hyperpyrexia, alteration of consciousness and convulsions. Laboratory examination showed an unusually high increase of serum transaminases, hyponatremia, and hypoxia. Neurologic abnormalities detected were hemiparesis and tetraparesis of the extremities, and second nerve atrophy; such abnormalities were found in 10 out of the 152 cases, or 6.5%. PMID- 1509882 TI - Neuropathology of HTLV-I-associated myelopathy--a report of two autopsy cases. AB - A neuropathological analysis was performed in two autopsy cases of HTLV-I associated myelopathy. The thoracic spinal cords were most severely affected and the histopathological findings consisted of mononuclear cell infiltration, marked destruction of myelin and axons and astrocytic gliosis. More than half the infiltrated cells were positive for pan-T cell marker; B cells were sparse in the parenchyma and subarachnoid spaces. CD4 and CD8 positive cells were found in the early stages of the lesions. CD8, however, predominated over CD4 in the other stages. It appeared that a chronic inflammatory process had started at the middle to lower thoracic cord and had extended gradually in both directions. The middle thoracic spinal cord is known to have the poorest blood supply, and the horizontal distribution of inflammatory cells at this region correlated with the most distal supply of the anterior spinal artery. PMID- 1509883 TI - Childhood neurocysticercosis--epidemiology, diagnosis and course. AB - Neurocysticercosis was diagnosed in 0.89% of children enrolled in our Child Neurology Clinic in the years 1979 to 1990. The commonest presenting symptom was seizures (90%) followed by raised intracranial pressure (44%). CT scans revealed a variety of lesions including low and high attenuation cysts, periventricular edema, hydrocephalus and calcification. ELISA was useful in substantiating the diagnosis in almost 70% of cases. Only 18 patients who had active disease merited treatment with praziquantel. The clinical and CT response was good. Follow-up revealed spontaneous quiescence in many patients with inactive disease. PMID- 1509884 TI - Human immunodeficiency virus infection in central nervous system and myeloid monocytic lineage. AB - We established persistent infection with a strain of human immunodeficiency type 1, HTLV-IIIB, in a ++promyelo-monocytic cell line, ML-1 (CD4 antigen nearly negative and CD4 mRNA negative), and a promonocytic cell line, THP-1 (CD4 antigen positive). Different reactions of giant cell formation were found after cocultivation of infected and uninfected cells of ML-1, HL-60, THP-1 and U-937 cell lines with uninfected and infected MOLT4 (a T-lymphoma cell line). Factors affecting the cellular tropism of human immunodeficiency virus were discussed. PMID- 1509886 TI - Head-down tilt bedrest. HDT'88 - an international collaborative effort in integrated systems physiology. PMID- 1509885 TI - Head-down tilt bedrest. HDT'88--an international collaborative effort in integrated systems physiology. AB - An international collaborative project, initiated by the DLR-NASA Life Sciences Working Group, led to the performance of a head-down tilt bedrest (HDT) study at the DLR Institute for Aerospace Medicine. Scientific and operational questions were addressed in preparation for the D-2 Spacelab mission. Principal areas of interest were cardiovascular regulation and fluid/electrolyte metabolism. The results are detailed in a series of 13 reports to which the present paper serves as an introduction. PMID- 1509887 TI - Effect of head-down bedrest on blood/plasma density after intravenous fluid load. AB - Using the mechanical oscillator technique, the mass density of antecubital venous blood and plasma samples was measured in 6 men before and after infusion of 22 ml/kg isotonic NaCl solution before, on day 7 during, and on day 3 after ten days of 6 degrees head-down bedrest. We studied 1) the distribution volumes of the infused NaCl solution, 2) the magnitude and time-course of induced fluid shifts to the extravascular spaces after rapid volume expansion, and 3) the protein concentration of the translocated fluid. The NaCl distribution volume was 16.7 +/ 2.9% body weight (BW) before, 15.0 +/- 3.0% BW during (P less than 0.05) and 13.0 +/- 1.3% BW after the head-down tilt (HDT) period (P less than 0.01). The volume of fluid shifted 120 min after infusion was not different in the control (12.9 +/- 7.4% plasma volume and 8.3 +/- 3.2% blood volume), during HDT (14.7 +/- 3.8% plasma volume and 7.4 +/- 5.6% blood volume), during HDT HDT conditions (14.6 +/- 2.2% plasma volume, and 8.2 +/- 1.3% blood volume, respectively). The density of the shifted fluid which reflects protein concentration was also unchanged (1004.2 +/- 4.2 g/l, 1002.6 +/- 4.3 g/l and 1003.9 +/- 8.2 g/l in the control, during, and after HDT periods, respectively). The mass density of red cells did not change with any condition. It is concluded that the distribution volume of isotonic saline solution decreases with diminished body mass. Densitometry provides a means of monitoring volume changes and protein shifts under the circumstances of our study. PMID- 1509888 TI - The effects of a 10-day period of head-down tilt on the cardiovascular responses to intravenous saline loading. AB - We tested the hypothesis that adaptation to microgravity, simulated by a 10-day period of head-down tilt (HDT), alters the responses to an intravenous fluid load by causing a larger fraction of the infused volume to be retained and magnifying the acute hemodynamic effects. HDT caused a significant (p less than 0.01) decrease in blood volume (-0.72 liters) and weight (-1.6 kg). Rapid infusion (22 ml/kg over 20 min.) of isotonic saline before, during, and after HDT produced a transient blood volume expansion with 18% of the infusate retained intravascularly after 2 hours. HDT had no effect on this response. Control hemodynamics were significantly different with lower cardiac output and higher total peripheral resistance (TPR) during and after HDT. Saline caused significant increases in cardiac output, heart rate, and stroke volume and a decrease in TPR. The magnitude and time course of these changes were not altered by HDT. The results refute the hypothesis and suggest that during HDT new set points or operating points were established for the control of intravascular volume and hemodynamic state. PMID- 1509889 TI - Effects of head-down tilt and saline loading on body weight, fluid, and electrolyte homeostasis in man. AB - We studied the effects of head-down tilt bedrest (HDT) on body weight, fluid and sodium homeostasis. A fluid load session with rapid intravenous infusion of 22 ml/kg body weight (BW) isotonic saline was performed before, during and after HDT. During the pre- and post HDT periods the test subjects were given a diet containing 2600 kcal/day. The energy intake was reduced to 2000 kcal/day during HDT. Water intake was kept constant at 40 ml/kg BW, sodium intake was 2.2 mmol/kg BW and protein intake was 1.4 g/kg BW, while the daily fat and carbohydrate intake was reduced during the HDT period. As expected plasma volume and BW changed rapidly in the beginning of HDT and during early recovery. A total body water loss of 0.6 l was observed within the second day after tilting. Plasma volume was reduced by 16% during HDT-bedrest. The time course of the body fluid loss paralleled a decrease in body sodium that then remained fairly constant during the HDT-bedrest period (except for the interference caused by the fluid loading on day S06). A restoration of body fluid and body sodium content occurred early in the recovery period. Fluid loading caused a negative fluid balance of 0.6-0.9 l over a 48 hr period following infusion regardless of the phase of the HDT study. These results demonstrate that under our strictly controlled conditions 1) HDT alters body fluid and sodium balances, 2) a standard fluid loading causes a net negative 3-day fluid balance during all phases of the study. PMID- 1509890 TI - Effect of head-down tilt bedrest (10 days) on lymphocyte reactivity. AB - Immunological responses of six healthy males to 10 days of head-down tilt bedrest (HDT) were assessed. Lymphocyte responsiveness was severely reduced immediately before, during, and immediately after the HDT, even though the lymphocyte numbers did not change. By contrast, delayed-type hypersensitivity was not affected. No dramatic changes were found in WBC counts and lymphocyte subpopulations, with the only exception of natural killer (NK) cells which transiently decreased immediately after HDT. Plasma cortisol levels were elevated above normal immediately before and during the HDT. The data suggest that the mitogenic response of lymphocytes was affected by psychological and fluid shift stress. These results are compared with data obtained during and after spaceflight. We conclude that the stress of HDT induces changes in immunological responsiveness that are strikingly similar to those arising from the stress of spaceflight. PMID- 1509891 TI - Cardiopulmonary function during 10 days of head-down tilt bedrest. AB - Pulmonary and cardiovascular responses to simulated weightlessness, i. e. 6 degrees head-down tilt bedrest (HDT) were investigated in six healthy male volunteers (mean age 26 yrs). Pulmonary diffusing capacity, functional residual capacity, pulmonary capillary blood flow, and lung tissue volume were measured by inert gas rebreathing. Heart rate and mean arterial blood pressure were obtained from finger blood pressure readings using a plethysmographic technique (Finapres). The short-term (20 min) response to HDT consisted of a 22% increase in pulmonary blood flow, and 13% and 31% falls in blood pressure and heart rate relative to standing. Functional residual capacity fell by 33%, while lung tissue volume increased insignificantly. Subsequent measurements during 10 days of HDT and 5 days of recovery revealed no further changes in lung volume, lung tissue volume, or blood pressure. However, diffusing capacity fell gradually and remained 4%-5% below baseline values after the 7th day of bedrest and during recovery (p less than 0.05). Pulmonary blood flow decreased by 16% during head down bedrest and recovered partially within the following 5 days (p less than 0.05). We conclude that during and after simulated weightlessness marked alterations in cardiovascular function and marginal affections of gas exchange can be demonstrated already at rest. They may be considered as contributing factors to orthostatic and exercise intolerance observed after space flight. PMID- 1509892 TI - Pulmonary responses to lower body negative pressure and fluid loading during head down tilt bedrest. AB - Exposure to microgravity redistributes body fluids with important secondary effects on cardiovascular function. We tested the hypothesis that the fluid shifts also affect pulmonary gas exchange. Microgravity was simulated in six male volunteers by a 10-day period of bedrest at 6 degrees head-down tilt (HDT). Lower body negative pressure (LBNP) and intravenous saline loading superimposed acute changes in fluid distribution on the prolonged effects of HDT. HDT produced relative dehydration and hypovolemia with decreased pulmonary blood flow and diffusing capacity. Before bedrest, pulmonary blood flow decreased by 24% during LBNP and diffusing capacity by 7%, while functional residual capacity increased by 14% (p less than 0.05). Intravenous saline loading caused a 24% increase in pulmonary blood-flow (p less than 0.05). Functional residual capacity decreased by 10% and diffusing capacity by 6% (p less than 0.05). Lung tissue volume did not change significantly. Head-down tilt had only minor effects on the responses to LBNP and saline loading. We conclude that LBNP and intravenous saline loading produce major changes in pulmonary blood-flow and minor effects on pulmonary gas exchange, and that the response to acute changes in fluid distribution is not significantly altered during simulated microgravity. PMID- 1509893 TI - Cardiovascular response to lower body negative pressure before, during, and after ten days head-down tilt bedrest. AB - The haemodynamic response to lower body negative pressure (LBNP) was studied in 6 test subjects before (baseline), during, and after (recovery) ten days of 6 degrees head-down bedrest. The LBNP protocol consisted of a 35 min control period, application of a staircase differential pressure profile (15 min at -15 mmHg; 5 min at -30 mmHg; 15 min at -40 mmHg), and a 10 min post-stress observation period. Cardiac output was measured by a foreign gas rebreathing technique. Finger plethysmographic arterial blood pressure (BP), ECG, and heart rate (HR), lower limb crossectional area, and the electrical impedance of three body segments were recorded continuously. As expected, HDT caused a decrease in plasma volume and total body fluid volume. Resting CO at the end of HDT was 16% below the baseline level and similar to CO in the upright position before HDT. Stroke volume (SV) was also reduced, but there were no significant changes in control HR or BP. Absolute changes in CO and SV during LBNP were similar at baseline and during HDT, but the relative changes were larger during HDT. HR and vasoconstriction responses were enhanced, but presyncope occurred in two subjects. Reduced cardiac filling with decreased stroke volume at rest is the apparent primary cause of the altered LBNP response during HDT. PMID- 1509895 TI - Influence of ten-day head-down bedrest on human carotid baroreceptor-cardiac reflex function. AB - We studied the effects of simulated microgravity on baroreceptor-cardiac reflex mechanisms, with complex pressure changes delivered to neck chambers worn by six healthy young men, before, during (days 1, 3, 6, and 10), and after ten days' 6 degrees head-down bedrest. During held expiration, a computer-driven bellows increased neck pressure to 40 mmHg for about 4 s, and then decreased pressure to 65, by 15 mmHg R-wave triggered decrements. We plotted R-R intervals as functions of carotid distending pressures (systolic less neck chamber pressures). Each experimental session comprised seven stimulus sequences delivered over about 15 min and averaged. Comparisons between results before bedrest and on the tenth day of bedrest showed that average baseline R-R intervals increased from 933 +/- (SEM) 24 to 1077 +/- 35 msec (P less than 0.05, Wilcoxon signed rank test); maximum slopes (R-R interval/carotid distending pressure) decreased from 4.5 +/- 0.4 to 3.6 +/- 0.7 msec/mmHg (P = 0.11); R-R interval response ranges decreased from 263 +/- 31 to 182 +/- 18 msec (P = 0.03); and operational points (positions of R-R intervals at resting pressures on the stimulus-response relation) remained constant. Our results suggest that head-down bedrest progressively impairs baroreceptor-cardiac reflex responses in healthy human subjects. PMID- 1509894 TI - Effects of head-down tilt for 10 days on the compliance of the leg. AB - The purpose of this investigation was to measure lower leg compliance before, during and after a 10-day period of bedrest at head-down tilt to test the hypothesis that leg compliance and the capacity for venous pooling is increased by the adaptation to stimulated microgravity. Venous occlusion plethysmography with multiple proximal occlusion pressures was used to obtain compliance measurements in six male subjects. Calf circumference decreased significantly during the tilt (corresponding to a decrease in cross sectional area of 7%) and had not returned to baseline seven days after the end of tilt. Compliance post tilt was significantly greater than pre-tilt, probably mainly due to a reduction in muscle mass. This study supports the need for investigations to define: (a) the degree of protection against orthostatic hypotension that can be achieved by maintaining leg muscle mass and tone, and (b) efficient and specific exercise programs to prevent loss of muscle mass and function-particularly during spaceflight. PMID- 1509896 TI - Influence of posture and prolonged head-down tilt on cardiovascular reflexes. AB - We investigated the influence of ten days 6 degrees head-down tilt (HDT) on short term cardiovascular control. To help differentiate between the effects of HDT induced fluid redistribution and changed autonomic cardiovascular modulation under prolonged HDT, the effect of acute posture changes was investigated as well. Six healthy male volunteers were studied. Continuous finger blood pressure was measured non-invasively by means of Finapres. Heart rate (HR) was derived from the electrocardiogram. Responses to forced breathing (FRSA), Valsalva's manoeuvre (VM), Mental Stress (MS) and Sustained Handgrip (SHG) were measured. Changing posture from HDT to standing enhanced the BP and HR responses to VM, both during straining and after release. During prolonged HDT, responses to VM changed toward the pattern seen in the upright posture before HDT, suggesting a strong influence of fluid redistribution. Neither posture nor prolonged HDT influenced HR variation during FRSA and responses to MS and SHG. BP variation during FRSA was influenced by posture but not by prolonged HDT. Thus, cardiovascular reflex tests which reflect the parasympathetic (FRSA) or the sympathetic (MS and SHG) efferents to the heart were not influenced by posture or prolonged HDT. Only the responses to VM were affected by both posture and prolonged HDT. These results are probably due to a decrease in blood volume and stroke volume under prolonged HDT, an increase in venous distensibility and, to a lesser extent, to inadequate cardiovascular regulatory responses. PMID- 1509897 TI - Increased orthostatic blood pressure variability after prolonged head-down tilt. AB - The effect of simulated weightlessness on orthostatic blood pressure regulation was evaluated with passive 70 degrees head-up tilt (HUT) after 10 days 6 degrees head-down tilt (HDT). Six healthy male volunteers were studied. Continuous recording of finger blood pressure (BP) was obtained non-invasively with a FinapresTM device. Instantaneous heart rate (HR) was derived from the electrocardiogram. To quantify orthostatic BP variability, a fast fourier transform (FFT) of the beat-by-beat BP- and RR-interval values was performed. Control HR before HUT after the 10-day HDT period was increased, probably due to an arousal state of the test subjects. The change in BP induced by HUT was not influenced by 10 days' HDT, in contrast to the HR rise which increased from 24 +/ 2 beats/min to 41 +/- 7 beats/min (P less than 0.05). After HDT the total variance in orthostatic BP almost doubled. FFT indicated that this increase in variance can be ascribed to BP oscillations with a frequency of around 0.1 Hz. In three subjects transient HR decelerations during HUT after HDT were observed. Analysis of the relationship between BP and HR in the transients showed that each HR decrease was preceded by a BP increase above normal. These HR decelerations seemed, therefore, to be an effect of the vagal part of the arterial baroreflex and did not necessary signal an impending vasovagal syncope. The present study indicates that although 10 days' HDT do not influence absolute BP responses to 70 degrees HUT BP was maintained by an increased sympathetic activity, reflected by an increased HR response and an augmented variance in BP around 0.1 Hz. PMID- 1509898 TI - [Limitations and perspectives of treatment with interleukin 2 (IL-2) in uro oncology]. PMID- 1509899 TI - [Tumor thrombosis in inferior vena cava: diagnostic imaging and therapeutic approximation]. AB - Review of our experience in the diagnosis and treatment of 44 patients with inferior vena cava tumoral thrombosis (IVCTT), associated or not to other neoplastic processes: 34 hypernephroma, 2 cava leiomyosarcoma, 1 paratesticular rhabdomyosarcoma and 1 biphasic synovial sarcoma. Twenty-five patients with hypernephroma and tumor thrombi in the ipsilateral renal vein only were excluded from the analysis since this fact did not change the usual therapeutic approach. In the 19 remaining patients, concomitantly to the primary tumour exeresis a thrombectomy was performed, using cavotomy with proximal and distal clamping in 11 patients and cardiopulmonary by-pass, deep hypothermia and cardiocirculatory arrest in 8 patients. The paper analyzes the radiological investigations performed in order to reach a IVCTT diagnosis, and reviews the related literature. PMID- 1509900 TI - [High pressure filling bladder]. AB - A complete urodynamic study was carried out on 41 consecutive patients presenting in the cystomanometry a vesical filling pressure at maximum capacity higher than 30 cm H2O. Two groups were evident: group I with neurogenic etiology, and group II without an obvious neurogenic etiology. From its results it can be seen that a diminished vesical accommodation is not a urodynamic fact restricted to vesicourethral neurogenic dysfunction, but it happens in several non-neurogenic conditions. Within the neurogenic group, the urodynamic element most frequently associated to a diminished vesical accommodation was an inferior motor neuron like vesicourethral dysfunction. An increased vesical filling pressure was not enough to produce urinary incontinence, being also necessary an added factor to prompt involuntary loss of urine. PMID- 1509901 TI - [Localized renal adenocarcinoma. Prognostic factors and influence of postoperative irradiation on survival]. AB - Presentation of our experience and results in the treatment of localized renal adenocarcinoma with radiotherapy supplementary to surgery. The influence of post operative radiotherapy in the subsequent occurrence of relapse and survival is analyzed. Also, the predictive value in our series of pre-surgery VSG, FA and LDH determinations is analyzed. PMID- 1509902 TI - [Bilateral renal carcinoma]. AB - Presentation of 9 patients with bilateral renal carcinoma, 8 synchronic and 1 asynchronic, diagnosed with intravenous urography, echography and/or CT and all of them treated, in the absence of metastasis, with either radical surgery of one kidney and conservative surgery of the other one, or with conservative surgery of both kidneys. Patients were followed-up until death. Four patients died of cancer, 3 for other reasons and 2 are still alive, mean survival 27.1 months. PMID- 1509903 TI - [Rigid ureteroscopy. Results and complications]. AB - Analysis of results and complications of retrograde rigid ureterorenoscopies (URS) performed in our unit between August 1985 and June 1990. Our series includes 122 URS performed in 106 patients: 68% female and 32% male. A rigid ureteroscopy Storz 11.5 Ch was used. URS indications were: 72% treatment of ureteral lithiasis, 14% diagnosis, 7% treatment of ureteral tumores and 3% other reasons. Treated lithiasis were predominantly located in the pelvic ureter. Overall success in the treatment of lithiasis was 92.86% in "primary" lithiasis, and 71.43% in post-ESWL. URS allowed us to resolve troubles of differential diagnosis in 93.75% of cases. With a complications rate of 19.7%, only 3.28% were considered relevant. PMID- 1509904 TI - [Diagnostic and therapeutic criteria of inverted papilloma]. AB - Seven cases of inverted papilloma (IP), two located at the UUT level and five in the bladder, one associated to transitional cells carcinoma. Treatment was conservative for the whole series, and neither co-adjunctive therapy or chemoprophylaxis was applied, except for the last case; after an average follow up of 19.8 months they all show complete remission. A discussion of urinary tract IP is suggested, studying the epidemiology, histology, pathogeny, clinical characteristics and diagnostic methods, of which endourological investigations are the most effective for a reliable diagnosis, since they allow direct visualization and biopsy sampling. Regarding the therapeutic options, the paper highlights the need for conservative surgery due to its benign biological behaviour. A strict control of the patients is necessary due to likelihood of recurrence and malignant transformation. PMID- 1509905 TI - [Congenital short urethra: surgical treatment]. AB - Presentation of 6 cases of congenitally short urethra seen in our Unit. The rarity of such malformation, as well as the difficulties to arrive to a presurgical diagnosis are emphasized. Also, review of surgical techniques described in the literature. Contribution of our experience in the use of the urethra's dissecting and elevating technique. We considered this the choice procedure except in extreme cases due to the good results obtained, fewer technical difficulties and lower risk of complications. PMID- 1509906 TI - [Monotherapy of ureteral calculi with extracorporeal shockwave lithotripsy]. AB - We reviewed our experience with ESWL in the treatment of 401 patients with ureteral stones in order to evaluate if a higher disintegration and clearance rates could be achieved without prior manipulation of ureteral calculi, i.e., ESWL used as "in situ" monotherapy. The global stone free rate were 83%, 85% and 91% at 15 days, 1 month and 3 months after ESWL. We also analyzed the results according to the efficiency quotient (EQ). PMID- 1509907 TI - [Urinary sepsis as manifestation of a renal angiomyolipoma]. AB - Renal angiolipomas are the most frequent benign renal tumours. Since ultrasound techniques have been in use to study algetic lumbar syndromes, their symptomatic appearance has decreased. Most authors agree that CAT has a 100% specificity. The paper contributes one case of renal angiomyolipoma isolated in a 39-year old woman, its primary interest being the clinical presentation, within an extensive septic milieu of urinary origin, the intra-operative diagnosis, considering the previous false-negative echography and dubious tomographic diagnoses, and the findings of regional node invasion, all exceptional states in the reviewed literature. PMID- 1509908 TI - [Spontaneous disappearance of pulmonary metastasis secondary to renal cell carcinoma after nephrectomy. Presentation of a case and review of the literature]. AB - Spontaneous disappearance of pulmonary metastasis is an occasionally occurring phenomenon, thus reflected in the literature. The article presents one case of spontaneous disappearance of pulmonary metastasis of clear cells renal carcinoma, histologically confirmed by fine needle puncture aspiration. After 36 months of follow-up, the patient shows no evidence of recurrence. PMID- 1509909 TI - [Metastatic renal carcinoma: regression of pulmonary metastasis and anemia after interleukin-2r immunotherapy]. AB - Presentation of one case of bilateral renal adenocarcinoma in a 63-year old female patient, undergoing surgical therapy by means of right radical nephrectomy and left partial nephrectomy. Within 6 months, the patient presented pulmonary metastasis and normocytic anaemia associated to paraneoplastic syndrome. After initiating treatment with Interleukin-2 in intravenous continuous infusion, both pulmonary metastasis and anaemia showed evidence of partial regression. PMID- 1509910 TI - [Erythrocytosis and renal adenocarcinoma]. AB - Contribution of one left renal adenocarcinoma in a 54-year old women, where the initial data was the finding of erythrocytosis discovered during routine laboratory tests performed by her gynaecologist. Review of the diagnostic and therapeutic procedures followed in this case, establishing a differentiation between erythrocytosis and polyglobulia. Normalization of the hemogram following extended nephrectomy is emphasized. This case history is considered to be of interest due to its presentation pattern. Finally, we believe that faced to an erythrocytosis of unknown etiology, a renal tumoral disease, more specifically a renal adenocarcinoma, should be suspected. PMID- 1509911 TI - [BCG in superficial carcinoma of the bladder. Authors' experience]. AB - Contribution of 95 patients with surface vesical tumour managed with UTR and endovesical BCG. The response was absence of recurrence in 68.4% cases in Ta stage, 63% in T1 and 66.7% in 'in situ' carcinoma. Therapy tolerability was good, with few side-effects. We conclude that BCG endovesical instillation as co adjunctive therapy to UTR in surface vesical tumours has been shown to be effective for the period under study. PMID- 1509912 TI - [Mannitol solution (M-400) vs. mannitol solution combined with allopurinol in the prevention of post-transfusion acute renal failure]. AB - Evaluation on the incidence of Acute Renal Failure (ARF) from a total of 41 corpse renal graft receptors, 20 of which received perfusion with mannitol solution at 400 mOsm/kg (Group 1) and 21 the same mannitol solution plus allopurinol (Group 2). No significant differences were present between both groups when they were analyzed for ARF incidence (15% vs 23.8%); overall incidence was 19.5%. 24-hour initial diuresis was shown to be an excellent predictor for long-term graft functionality. We can conclude that the addition of mannitol to the perfusion solution contributes decisively to reduce post transplantation ARF, while addition of allopurinol does not have further beneficial effects. PMID- 1509913 TI - [Complete hormonal blockade vs. monotherapy in the management of metastasizing prostatic cancer]. AB - Evaluation of results obtained in 70 hormone-treated patients with disseminated prostate cancer. Thirty-six of them were treated via orchiectomy and 34 received also flutamide. Initial objective response rates were 47% in the monotherapy group versus 58% for those undergoing complete blockade. Decrease of PSA and PAP was also higher in the group given flutamide. Nonetheless, no significant changes were observed with regard to biological and clinical progression or patients survival. PMID- 1509914 TI - [Epidemiology of urinary calculi in the Marina Alta (Alicante) region]. AB - An epidemiological study on urolithiasis was conducted in the Borough of Marina Alta from December 1989 to December 1990. The Health Care region of Marina Alta includes 11 health care areas, all centralized into one single Local Hospital offering service to an estimated population of 125,290 inhabitants, which experiences a remarkable increase over the summer months. During the study period 1,792 patients, 350 (20%) of which were lithiasis cases were seen in the Urology Unit. 2.80 per thousand of the studied population had urolithiasis-related signs. Incidence is higher in males than in females, as well as in patients with prior lithiasic diseases, surgery and urinary infections. Urinary infection was present in 20% of patients. Nine percent of patients had some type of associated urinary malformation. The most frequent mineral composition of the lithiasis was: Calcium oxalate (52%), uric acid (20%) and oxalate plus uric acid (9%). PMID- 1509915 TI - [Urethral sonography in the diagnosis and preoperative evaluation of urethral stenosis]. AB - An area of spongiofibrosis can be found proximal and distal to all stenosis of the urethra. The severity of such spongiofibrosis as well as its length are in many instances decisive when choosing an adequate surgical approach. Conventional radiological diagnosis of stenosis of the urethra only shows the area of urethral stricture but is unable to inform on the fibrosis of the spongy body. Sonourethrography or urethral echography affords a dynamic tridimensional examination of the anterior urethra which provides accurate data on the length of the stenosis, as well as the extend and severity of the spongiofribosis. Sixteen patients diagnosed with stenosis of the urethra through sonourethrography were evaluated. This easy-to-perform investigation, allowed the identification of 4 patients with peristenotic intense spongiofibrosis, hypercongenital urethra, who underwent open urethroplastia. The urethra of another 3 patients showed normal echogenicity, but diminished elasticity, and were diagnosed as of moderate spongiofibrosis requiring extensive internal urethrotomy. We believe sonourethrography should become a procedure to be included as part of the routine pre-surgical investigation of the stenosis of the urethra due to its non-invasive nature, easiness to perform, and because it provides highly useful information which would allow a decreased number of re-stenosis following surgery of the urethral stenosis. PMID- 1509916 TI - [Extracorporeal shockwave lithotripsy: an alternative treatment for lithiasis of caliceal diverticula]. AB - Among all the patients treated in our Lithotrity Unit, 13 of them had lithiasis inside the calyceal diverticulum. They were all treated by extracorporeal shockwaves. In none of the cases complete expulsion of lithiasic mass was achieved. In 3 (23%) cases it was reduced to half. In 2 (15.3%), 75% of the initial mass remained; and in 8 (61.5%) stones were fragmented but none of their debris was eliminated. Out of all the patients who were symptomatic before starting treatment, only 36.6% become asymptomatic. Extracorporeal lithotrity is, therefore, an approach with limited results in the calyceal intradiverticular lithiasis. PMID- 1509917 TI - [Echodensitometry: a new echographic diagnostic possibility]. AB - The determination and quantification of grey levels in the echography scale, designated by some authors Echodensitometry, is viewed as a new method for diagnosis using ultrasound techniques. This paper advances the results from a study conducted with an echographer equipped with an echographic density measuring device. This model analyzes the number of pixels in the image showing the most frequent level of grey. Normal and pathological parenchymatous urological organs (kidney, prostate and testicle) have been examined. Normal organs show a gaussian distribution of grey with a predominant level of typical grey for each of them. When affected by an acute inflammatory process the organs maintain their gaussian distribution but the predominant grey is lower (darker) due to the edema and the hyperaemia. When the inflammatory process becomes chronic, distribution, although somewhat irregular, is still gaussian but with higher predominance of grey (lighter) probably due to the fibrosis. The tumoral cases of our study also showed a gaussian curve even more irregular and with levels of variable grey. When specific areas of the tumour are analyzed the findings are very distinct depending on whether the areas are hypo or hyperechoic. Hyperechoic areas produce highly irregular maps. Research should be directed to provide more complex, although easy to perform systems of analysis which can correlate adequately with the histological study. It would be desirable that the equipment would be standardized to allow analysis of 'in vitro' images. If and when these objectives can be accomplished we would be able to venture into an echography histological diagnosis, something nowadays yet impossible. PMID- 1509918 TI - [Ureteral lithiasis. Analysis of 3 series]. AB - Presentation of our experience on 1000 cases of ureteral lithiasis treated over the last five years with ESWL, ureteroscopy and ureterolitotomy, distributed in three series of 396, 265 and 339 cases respectively. In the first series (396 cases), lumbar ureter calculi were treated with ESWL (dornier HM3) and iliopelvian calculi with ureteroscopy. In the second series (265 cases), all calculi were treated with ESWL (Siemens Lithostar). The third series was in turn subdivided in three groups: in the first group, comprising simple ureteral calculi, 'in situ' ESWL was performed; in the second group, of lumbar ureter complex calculi, ESWL was performed assisted by simple endourological techniques; ureteroscopy was performed in the third group, iliopelvian ureter complex calculi. Calculi characteristics (site, size, consistency and number), excretory tract and renal function, designated as CEP/LTS-X were assessed. These parameters allow us to grade ureteral lithiasis in Types I, II and III. A comparative study of the results in the three series was made reaching an overall conclusion that simple or Type I ureteral lithiasis can be treated with 'in situ' ESWL as first choice; in Type II or lumbar ureter complex lithiasis, 'in situ' ESWL is insufficient and other endoeurological support techniques are required, while in Type III, iliopelvian ureter complex lithiasis, ureteroscopy should be recommended. PMID- 1509919 TI - [Can we do without bone gammagraphy in the staging of prostatic cancer?]. AB - Correlation between findings on bone gammagraphy and PSA levels in 144 patients with untreated prostate cancer are analyzed. With prevalence of metastatic disease in 57.6% cases and considering the predictive cut value of metastasis to be 20 ng/ml, there were positive and negative predictive values of 64.9% and 73.9%, with a diagnostic confidence of 66.6%. We conclude that bone gammagraphy is essential for staging prostate cancer even in patients with PSA below 20 ng/ml. PMID- 1509920 TI - [Percutaneous treatment of a mycotic renal abscess, caused by Aspergillus fumigatus, in an AIDS patient]. AB - Presentation of one case of renal mycosis by Aspergillus as a primary complication in one patient diagnosed with acquired immunodeficiency syndrome. The importance of conservative treatment at all costs through percutaneous drainage is underlined, specially if we considered the short life expectancy of patients who have developed AIDS. PMID- 1509921 TI - [Encrusted cystitis. Review of the literature and report of a case]. AB - Alkaline encrusted cystitis is an infrequent process, almost forgotten by urologists. It tends to appear complicating an underlying cystopathy. Consists in a vesical inflammatory state, characterized by precipitation and incrustation of calcareous (phosphate, carbonate) and ammonium-magnesium salts on the vesical mucosa, their genesis being conditioned by the existence of pre-existing mucosa damage, urinary infection by urolithic microorganisms and alkaline urine. The present paper discloses an exceptional case of incrusted cystopathy with alkaline urine associated to uroinfection by E. coli (microorganism of uncertain and questionable urolithic activity). Treatment with urinary antiseptics, acetohydroxamic acid associated with curettage and UTR of calcareous plates was resolutive. With regard to the present cases, we review the limited literature available on the coexistence of incrusted cystitis and E. coli uroinfection and discuss the mechanisms through which E. coli could induce formation of lithiasis and incrustations in the urinary tract. PMID- 1509922 TI - [Results of treatment with interferon and vinblastine in renal cancer]. AB - Contribution of our experience with Alpha-2a Interferon and Vinblastine, for the treatment of advanced renal cancer in patients formerly not treated with nephrectomy. Pathoanatomical diagnosis was confirmed by puncture biopsy. None of the 4 patients recruited in the protocol showed objective response. In 2 patients no change was observed and in the other 2 the disease progressed. In surviving patients it was impossible to sustain therapy for more than three months. Treatment was discontinued as a result of the Interferon side-effects, such as fever, myalgia, asthenia and neuritis. PMID- 1509923 TI - [Percutaneous drainage of renal and perirenal abscesses]. AB - The prevalence of renal and perinephritic abscesses has radically changed over the last few decades basically due to two causes: the efficacy of antibiotics and early diagnosis by echography and/or CAT. Between January 1986 and December 1990, 12 cases of renal abscesses have been diagnoses in our Unit which have been treated conservatively through therapy with antibiotics and lumbar percutaneous drainage. Only one case was resolved with antibiotics alone; all other 11 cases needed drainage, in spite of a improvement in the symptoms, which was performed by translumbar puncture. Drainage was effective in 10 cases and the cultures found 5 cases of E. coli, 4 cases of Staphylococcus aureus and 1 case of Gram(-) bacilli. In the two cases where percutaneous drainage was not effective abscesses were produced by fungi: C. albicans and Mucor mycosis which caused highly solid septum and sphacelus requiring in both cases the use of open surgery. Currently this disease no longer represents a serious problem, it has a minimal morbidity and no mortality; only the group of high risk immunosupressed patients (AIDS, HIV (+), ADVEP) shows an increase in the number of cases and management in these patients continues to be problematic. PMID- 1509924 TI - [Transitional cell tumor of the bladder in childhood]. AB - Presentation of one case of transitional cells tumour of the urinary bladder in a 10-year old patient. We emphasize the rarity of such tumours during the first decade of life as well as their good prognosis, the only management required being just an endoscopic resection. PMID- 1509925 TI - Suppression of voluntary alcohol intake in rats and alcoholics by gamma hydroxybutyric acid: a non-GABAergic mechanism. PMID- 1509926 TI - Treatment of panic disorder. PMID- 1509927 TI - WALTHAM: its aims and achievements. PMID- 1509928 TI - Taurine and Taisho Pharmaceutical Co., Ltd. PMID- 1509929 TI - Review: taurine deficiency and the cat. PMID- 1509930 TI - Review: myocardial physiological effects of taurine and their significance. PMID- 1509932 TI - Taurine attenuates contracture induced by perfusion with low sodium, high calcium medium in chick hearts. PMID- 1509931 TI - Sarcolemmal actions of taurine linked to altered phospholipid N-methylation. PMID- 1509933 TI - Amino acid interaction with taurine metabolism in cats. PMID- 1509934 TI - Effect of taurine on intracellular calcium dynamics of cultured myocardial cells during the calcium paradox. PMID- 1509936 TI - Effects of taurine deficiency on arrhythmogenesis and excitation-contraction coupling in cardiac tissue. PMID- 1509935 TI - Intracellular effects of taurine: studies on skinned cardiac preparations. PMID- 1509937 TI - Taurine potentiates the antiaggregatory action of aspirin and indomethacin. PMID- 1509938 TI - Mechanism underlying physiological modulation of myocardial contraction by taurine. PMID- 1509939 TI - Effects of taurine depletion on membrane electrical properties of rat skeletal muscle. PMID- 1509940 TI - Regression of taurine depletion in rhesus monkeys deprived of dietary taurine throughout the first year. PMID- 1509941 TI - Taurine transport in the mouse cerebral cortex during development and ageing. PMID- 1509942 TI - Phospholipids, phospholipid methylation and taurine content in synaptosomes of developing rat brain. PMID- 1509944 TI - The effect of dietary supplementation with cysteic acid on the plasma taurine concentration of cats maintained on a taurine-restricted diet. AB - The biochemical impairment in the taurine anabolic pathway of the cat has not yet been fully elucidated; however, a number of key enzymes are known to have reduced activity in the cat compared to the rat. There are a series of possible routes resulting in the formation of taurine, one of which is the decarboxylation of cysteic acid. The aim of this study was to investigate the effect of cysteic acid, as a precursor, on the circulating concentration of taurine. A group of twelve adult cats was fed a basal, canned diet containing 0.22 g taurine/kg fresh weight for a period of eighty-four days. The diet was supplemented with 2.0 g/kg fresh weight L-cysteic acid on day fifteen through fifty six and plasma taurine concentration was measured every two weeks throughout the study. The results showed that when the dietary intake of taurine was inadequate to maintain the plasma concentration above 40 mumol/L, the addition of L-cysteic acid to the diet gave rise to an increase in plasma taurine concentration in some cats. Eight of the twelve cats showed a significant rise in plasma taurine after dietary supplementation for six weeks (52.0 +/- 22.3 vs 212.4 +/- 97.9 mumol/L, p less than 0.01) and a subsequent decrease in plasma levels when the cysteic acid was withdrawn (65.6 +/- 37.1 mumol/L). The other four cats showed no significant rise in plasma taurine after six weeks supplementation (13.5 +/- 4.2 vs 35.5 +/- 19.4 mumol/L, ns). However, withdrawal of the cysteic acid resulted in a subsequent decrease in circulating levels of taurine (11.8 +/- 1.5 mumol/L, ns). These data indicate that the addition of cysteic acid to a taurine-restricted, canned diet will, in some cats, result in the biosynthesis of taurine. The plasma taurine concentration of the remaining cats, although not apparently increasing significantly, was maintained at a slightly higher constant level until the cysteic acid was withdrawn. These results suggest that cats are able to synthesise taurine via an alternative pathway utilising L-cysteic acid as a precursor, although the efficiency of this process differs considerably among individual animals. PMID- 1509943 TI - The effect of taurine on the age-related decline of the immune response in mice: the restorative effect on the T cell proliferative response to costimulation with ionomycin and phorbol myristate acetate. AB - 1. Proliferative responses to the costimulation with phorbol-12-myristate-13 acetate (PMA) and suboptimal doses of ionomycin in the purified T and B cells from old mice were lower than those from young mice. 2. The degree of the age related decline was more significant in T cells than in B cells. 3. Taurine, a sulfur containing amino acid, augmented the proliferative responses of T cells from both young and old mice. 4. The augmentation of the proliferative response by taurine was more marked in old T cells than in young T cells. 5. The concentration of intracellular free calcium ion ([Ca2+]i) was significantly lower in old T cells when stimulated with PMA and ionomycin than observed in young T cells. 6. In the presence of taurine, the concentration of [Ca2+]i in the old T cells significantly increased under stimulation by PMA and ionomycin. 7. The results indicate that taurine improved the proliferative response in old T cells by restoration of the increment of the concentration of [Ca2+]i under the stimulation by PMA and ionomycin. PMID- 1509945 TI - Effects of taurine deficiency on immune function in mice. PMID- 1509947 TI - Pathologies of the CNS and associated taurine changes. PMID- 1509946 TI - Review: recent studies on taurine in the central nervous system. PMID- 1509948 TI - Effect of Hepes on the uptake of taurine by cultured nervous cells. PMID- 1509949 TI - The trophic role of taurine in the retina. A possible mechanism of action. PMID- 1509950 TI - Localization of taurine and glial fibrillary acidic protein in human optic nerve using immunocytochemical techniques. PMID- 1509951 TI - Effects of taurine on protein phosphorylation in mammalian tissues. PMID- 1509952 TI - The metabolic basis for the taurine requirement of cats. PMID- 1509953 TI - Taurine protects against oxidant injury to rat alveolar pneumocytes. PMID- 1509954 TI - The protective effect of taurine on the biomembrane against damage produced by the oxygen radical. PMID- 1509955 TI - Volume regulatory fluxes in glial and renal cells. PMID- 1509956 TI - Cell volume changes and taurine release in cerebral cortical slices. PMID- 1509957 TI - Taurine and volume regulation in isolated nerve endings. PMID- 1509958 TI - Hyperosmolarity and taurine content, uptake and release in astrocytes. PMID- 1509959 TI - Characteristics of taurine transport in cultured renal epithelial cell lines: asymmetric polarity of proximal and distal cell lines. AB - Taurine transport was determined in two continuous, renal epithelial cell lines: LLC-PK1 derived from the proximal tubule of the pig, and the Madin-Darby canine kidney cell (MDCK) from the distal tubule of the dog. In LLC-PK1, taurine transport is maximal at the apical surface, whereas in MDCK cells, transport is greatest at the basolateral surface. Transport is highly dependent on both sodium and chloride in the external medium, and is specific for beta-amino acids. The apical and basolateral surfaces of both cell lines show an adaptive response to extracellular taurine concentration, but only the basolateral surface of the MDCK cell responds to hyperosomolality by increased taurine accumulation. Thus, differential control of the beta-amino acid transport system by substrate and external tonicity exists. The role of the beta-amino acid transport system may differ according to the origin of the cell: in the proximal renal tubular cell, net transepithelial reabsorption of filtered taurine increases the body pool. By contrast, taurine accumulation by distal tubular cells may form a mechanism of cell volume regulation in response to osmotic stress. PMID- 1509960 TI - Metabolism of cysteine to taurine by rat hepatocytes. PMID- 1509961 TI - Recent developments in assays for taurine, hypotaurine and some metabolic precursors. PMID- 1509962 TI - Anion-exchange HPLC of taurine, cysteinesulfinate and cysteic acid. PMID- 1509963 TI - Hypotaurine in male reproduction. PMID- 1509964 TI - Intestinal taurine and the enterohepatic circulation of taurocholic acid in the cat. PMID- 1509965 TI - Urinary excretion of taurine as a function of taurine intake: potential for estimating taurine bioavailability in the adult cat. AB - Urinary taurine excretion increases markedly when excess taurine is consumed. Experiments were designed to characterize this response in an attempt to develop an assay system for taurine bioavailability in common cat foods using an adult cat model. Initial studies investigated the time course of changes in urinary taurine excretion in response to alterations in taurine intake. The rate of urinary taurine excretion decreased rapidly when cats were switched from a casein diet supplemented with 0.2% crystalline taurine to a diet containing no supplemental taurine, reaching steady-state in 2 d. In contrast, urinary taurine excretion by cats switched from low to high taurine did not plateau until 6 to 7 d. Subsequently, cats (n = 18) were fed a casein diet containing graded levels of crystalline taurine (0, 0.025, 0.05, 0.10, 0.15 or 0.20%). After a 7-d adjustment period, urinary taurine excretion was quantified over a 5-d collection period and also by cystocentesis, and blood taurine levels were measured on d 6. Plasma taurine increased linearly (r = 0.88) as taurine intake increased, while whole blood taurine increased asymptotically, reaching 95% of maximum concentration at a taurine intake of 93 mu mole/(kg body weight.d). The rate of urinary taurine excretion increased only slightly as taurine intakes increased to 96 mu mol/(kg body weight.d), but increased markedly (15-fold) thereafter. The same pattern was observed whether urinary taurine excretion was expressed as mu mole/(kg body weight.d) from total urine collection or as mu mole/g creatinine from cystocentesis.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1509966 TI - Taurine synthesis in cat and mouse in vivo and in vitro. PMID- 1509967 TI - Reduction of intrinsic contractile function of the left ventricle by taurine deficiency in cats. PMID- 1509968 TI - High dietary taurine and feline reproduction. PMID- 1509969 TI - Taurine distribution in the cat muscle: an immunohistochemical study. PMID- 1509971 TI - Differential effects of dipyrone, ibuprofen, and paracetamol on experimentally induced pain in man. AB - In a double-blind cross-over study on 22 healthy subjects the analgesic efficacies of the antipyretic analgesic drugs ibuprofen, dipyrone and paracetamol were tested against placebo using a model of experimentally induced pain. To this purpose interdigital webs were pinched repeatedly for 2 min periods. The painfulness of these stimuli was assessed by the subjects on an electronically controlled visual analogue scale at 10 sec intervals. In addition to the subjective pain ratings the stimulus induced reflex diminution of the blood flow in the stimulated hand was measured with photoplethysmography and laser Doppler flow analysis. The flare response around the stimulated area was assessed with infrared thermography. In this assay system ibuprofen and dipyrone, but not paracetamol, showed statistically significant analgesic effects by preventing hyperalgesia which is normally induced by the repeated stimulation of a skin site. This hypoalgesic effect was not related to the subjective impression of the subjects of the analgesic potency of the respective drug. Sympathetic reflex vasoconstriction was not quantitatively related to the drug induced hypoalgesia. Ibuprofen and, to a minor extent, the other antipyretic analgesic drugs also diminished the stimulus induced flare reaction around the stimulated skin sites. PMID- 1509970 TI - Long-term treatment of the MRL/lpr mouse with methotrexate and 10 deazaaminopterin. AB - Female MRL/lpr mice were treated with I.P. doses of methotrexate (MTX) and 10 deazaaminopterin (DAAM) in the range of 1 to 100 mg/kg body weight/week, in two equally divided doses. Treatment began at 7 weeks of age and continued to 30 weeks of age. Joint histopathology scores were tightly correlated with skin lesion-proteinuria scores at 30 weeks of age. MTX at levels of 5, 25, and 100 mg/kg body weight/week and DAAM at a level of 25 mg/kg body weight/week significantly reduced skin lesion-proteinuria scores below controls in a dose dependent manner. Animals receiving MTX at 25 mg/kg body weight/week had a significantly longer median life span and animals receiving MTX at 100 mg/kg body weight/week had a greater than 15% suppression of growth when compared with controls. Longevity and skin lesion-proteinuria scores appeared to be good indicators of drug efficacy while growth suppression appeared to be a good indicator of drug toxicity. PMID- 1509972 TI - Calcium channel blockers prevent stress-induced ulcers in rats. AB - Gastric mucosal damage induced by cold and restraint stress caused increase in gastric lipid peroxidation (LP) and decrease in gastric glutathione levels. Two calcium-channel blockers, verapamil and nicardipine, prevented stress-induced increase in gastric LP, as well as ulcer formation. Both calcium-channel blockers protected against stress-induced ulcers, and inhibition of LP may be among their mechanisms of action. PMID- 1509973 TI - The inhibitory action of ethanol on the gastric mucosa and its interaction with the vagus in rats. AB - The influence of systemic ethanol and/or the vagus on ionic secretion and on glandular mucosal blood flow (GMBF) was studied in an ex-vivo gastric chamber preparation in rats. Sub-diaphragmatic vagotomy decreased H+ secretion and Na+ outflux from the gastric mucosa. Subcutaneous injection of 50% ethanol significantly potentiated these responses, but not the concentrations of 25% and 100%. The three doses of ethanol did not affect the secretion of both H+ and Na+ in vagus-intact animals. Ethanol, however dose-dependently reduced the GMBF in both vagus-intact and sub-diaphragmatic vagotomised rats, and the effect was greater in the latter-operated animals. It is concluded that vagus nerves greatly influence the secretion of both H+ and Na+ the gastric mucosa but the effect is unrelated to GMBF. Systemic ethanol reduced the secretion of these ions only in vagotomised animals, indicating the vagus could play a role in modulating the action of ethanol in the stomach. PMID- 1509974 TI - The influence of age, sex and race on salivary kallikrein levels in human mixed saliva. AB - Variation in the level of salivary kallikrein in human saliva has been reported as a function of systemic conditions such as reduced salt intake and during the menstrual cycle. Higher levels of salivary kallikrein have been observed in subjects with tumors distant from the oral cavity when compared to control subjects. These studies have not evaluated factors, such as age, which might influence the concentration of glandular kallikrein in saliva. The purpose of the present study was to determine the variation of salivary kallikrein concentration as a function of age. Differences attributable to sex or race were also evaluated. Mixed saliva was collected from 114 subjects, ages 5-91, by paraffin stimulation. Samples were centrifuged and stored at -20 degrees C for subsequent analysis. Glandular kallikrein activity was assayed using D-ValylLeucylArginine-p nitroanilide as the substrate. In a linear regression model which included sex, race, and age, levels only the factor of age had a significant effect on kallikrein levels. The p-value for the reduced model including only the factor of age was 0.0406 and the R-square was 0.038. Further analysis revealed that females did exhibit significantly higher kallikrein in individuals 40 years or older and that the effect of age appeared to be limited to females. It is concluded that both gender and age must be considered when evaluating salivary kallikrein changes in relationship to systemic disease. PMID- 1509975 TI - Structural and functional properties of heat-shock proteins in inflammation and immunity. European workshop on inflammation. Airport meeting, March 15, 1991. Frankfurt airport, Germany. PMID- 1509976 TI - Joint international meeting: 3rd meeting on side effects of anti-inflammatory drugs and 13th European Workshop on Inflammation 8-11 May, 1991. Verona, Italy. PMID- 1509977 TI - In vitro effects of PAF on venous endothelial cell actin disposition. AB - Venous endothelial cells have been stained in vitro for the contractile protein actin, using an immunofluorescence technique. Semi-automated image analysis showed that treatment with platelet-activating factor (PAF 5 x 10(-7) M) caused elongation of endothelial cells and alteration in their actin-staining characteristics. These changes are prevented by the PAF antagonist BN52021 (1 x 10(-5) M and 1 x 10(-6) M) and the absence of extracellular Ca++. It is suggested that it is the resultant decrease in intracellular Ca++ levels which is responsible for preventing the effects of PAF. PMID- 1509978 TI - Acute pulmonary toxicity of inhaled beta-1,3-glucan and endotoxin. AB - The number of inflammatory cells was studied in lung walls and airways after inhalation of endotoxin or beta-1,3-glucan. In the water unsoluble form, beta-1,3 glucan caused a delayed response in terms of a decrease in macrophages and lymphocytes in the lung wall, 1 to 7 days after exposure but no invasion of neutrophils into the airways. When solubilized in 0.02 N NaOH, the cell response was the same as that observed after exposure to endotoxin. PMID- 1509979 TI - The effects of flurbiprofen on the passive transfer of adjuvant-induced arthritis. AB - The effect of flurbiprofen on the passive transfer of adjuvant-induced arthritis was studied to determine if flurbiprofen acted in the donor and/or recipient arms of this model. Groups of donor and recipient rats were treated with either placebo or flurbiprofen 4 mg/kg. Joint scores were markedly decreased in recipient rats treated with flurbiprofen irrespective of the whether donor animals were treated with placebo or flurbiprofen (p less than 0.01). There was also a moderate decrease in the ability of donor cells from rats treated with flurbiprofen to suppress the severity of arthritis (p less than 0.01); however, this effect was less marked than that seen in recipient animals. These data imply that flurbiprofen may act at multiple sites in adjuvant-induced arthritis, but the major site of action of flurbiprofen in this model is in the recipient animals. PMID- 1509980 TI - Evidence that endogenous interleukin-1 is involved in leukocyte migration in acute experimental inflammation in rats and mice. AB - As a putative mediator of inflammation interleukin-1 has been implicated in the recruitment of leukocytes during the early stages of the inflammatory reaction. In the present report we have investigated the release of endogenous IL-1 in the rat zymosan pleurisy and in the mouse zymosan peritonitis. In both cases the release of the cytokine was maximal 4 hours after zymosan injection and appeared to be time-related to neutrophil migration into the inflammatory site. The effect of in vivo treatment with dexamethasone in rat pleurisy and with polyclonal anti murine IL-1 beta antibody in mouse peritonitis was also assessed. The steroid reduced both cell migration and the release of IL-1-like activity as well as the formation of exudate and the release of eicosanoids. The anti-IL-1 beta serum inhibited selectively the number of neutrophil that migrated to the inflamed site (approximately 40%) and the IL-1 activity recovered in (approximately 70%) the exudate. In vitro incubation of the inflammatory exudate with polyclonal anti murine IL-1 alpha or anti-murine IL-1 beta sera allowed the identification of the IL-1 species present. In the rat pleurisy IL-1 biological activity was mainly due to the alpha species, whereas IL-1 beta was the only species apparently present in the mouse peritoneal exudate. PMID- 1509981 TI - Biological activity of prostaglandin E3 with regard to oedema formation in mice. AB - The biological activity of PGE3 with regard to oedema formation in mice was examined. Paw swelling was measured 30 minutes after injection of 10 microliters PGE2 or PGE3 into the plantar region of the hind paw. Doses investigated ranged from 1 ng-10 micrograms. Both PGE2 and PGE3 had substantial oedemogenic activity in this system. PMID- 1509982 TI - Characterisation and pharmacological sensitivity of antigen arthritis induced by methylated bovine serum albumin in the rat. AB - The optimum conditions for the induction of antigen-induced arthritis in the rat have been studied. Two immunisations with methylated bovine serum albumin (mBSA) (0.5 mg) in Freund's complete adjuvant (FCA) containing 0.375 mg Mycobacterium tuberculosis followed by an intra-articular injection of mBSA (0.5 mg) led to the production of a chronic, erosive arthritis. The development of the arthritis was associated with the appearance of T lymphocytes and other inflammatory cells in the synovium. Male and female animals were equally susceptible to the disease. Prednisolone, indomethacin and methotrexate inhibited the development of the arthritis but ibuprofen and D-penicillamine were without any significant effect. PMID- 1509983 TI - [Sensitivity and specificity of the determination of IgE using chemiluminescence (CLA allergy test)]. AB - We studied 80 patients. All patients underwent a thorough clinical evaluation, including a comprehensive study and physical examination of the ear, nose, throat and chest. Each patient underwent prick testing and a nasal provocation test. In addition, blood was drawn for the allergen-specific IgE test (RAST) and total serum IgE levels. We selected 11 allergens for this study: grass (Dactylis glomerata-orchard grass, Phelum pratense-Timothy grass, Lolium-raygrass), weeds (Chenipodium, Parietaria), tree (European olive), dog, cat, mites (D. pteronyssinus, D. farinae) and mould (Alternaria). To evaluate the efficiency, specificity and sensitivity of this method, test results obtained in our centre were compared to the clinical standard. Sensitivity is related to the lowest concentration of specific IgE detected by test method. Specificity is related to the antibody test's ability to detect the specific substance being measured without interference from related molecules. Chemiluminescent assay system (CLA) demonstrated a good balance between sensitivity and specificity and was consistent for the following allergens: D. pteronyssinus, D. farinae, Parietaria pollen and Gramineae pollena. PMID- 1509984 TI - [Evaluation of the nasal provocation test in perennial allergic rhinitis. I. Rhinitis caused by mites]. AB - Parametres of clinical usefulness of the two cutaneous tests, RAST and NPT, are analysed and compared with DPT in two series of patients. Our data show the efficacy of NPT in the diagnosis of allergic perennial rhinitis. PMID- 1509985 TI - IgG subclass deficiencies and recurrent pyogenic infections, unresponsiveness against bacterial polysaccharide antigens. AB - In patients suffering from recurrent or chronic infections with encapsulated bacteria the humoral immune disorder of IgG subclass deficiencies is common (about 20%), yet insufficiently diagnosed because of the nonspecific symptomatology and the often unaffected levels of total immunoglobulin (Ig) isotypes. IgG subclass deficiency is correctly diagnosed by measurement of all four IgG subclasses. The IgG2-subclass deficiency is most frequent, often together with decreased IgG4- and/or IgA-levels. The IgG2-subclass deficiency is associated with a diminished immune response to (bacterial capsular) polysaccharide antigens. Although the anti-polysaccharide response is generally believed to be IgG2-restricted, a causal relationship between a decrease in IgG2 and disease is obscure. First, the precise meaning and contribution of IgG2 to the opsonization of encapsulated microorganisms is incompletely known. Second, several healthy individuals completely lack one or more isotype/subclasses due to (pseudo-) deletions of the genes, but still produce protective antibody titers in the residual Ig isotype or subclass. Third, young children mount protective titers of specific IgG1 antibodies against polysaccharides, whereas IgG2-subclass deficient children are prone to infection by encapsulated bacteria. In sum, decreases in IgG2 subclass levels may be merely epiphenomenal in a large group of patients who do not respond effectively to (bacterial) polysaccharides. New directions of investigation in order to obtain insight in the prevalence and pathogenesis of IgG subclass deficiencies are discussed. PMID- 1509986 TI - [Immunologic clinical evaluation of a biological response modifier, AM3, in the treatment of childhood infectious respiratory pathology]. AB - To assess the immunoclinical effectiveness of a biological response immunomodulator, we used AM3 (glycophosphopeptide ), a glucomannan polysaccharide extracted from the cell wall of a strain of Candida utilis, in 20 children with asthmatic bronchitis. They received 2 envelopes (1 g) daily for 4 months. The results were compared with a control group of 20 untreated children with the same pathology. The following clinical and immunological parameters were assessed in all of them: cough, dyspnea, expectoration, frequency and intensity of the bronchospasm, time of administration of the symptomatic medication, and the delayed cutaneous cells response by means of the intradermal reaction of 5 antigens (Trichophyton, Candida albicans, tuberculin, E. coli and bacterial antigens). In the treated group, the immunoferon (AM3) reduced the symptoms, the intensity and frequency of the bronchospasm, and the symptomatic medication (table I, II and III). In basal conditions, the 40 children presented a state of 75% anergy; after 4 months of treatment, the treated group experienced a 45% decrease in their anergic situation, variation which was statistically significant when compared with the control group. In our 20 treated patients, AM3 behaved like and immunostimulant, improving the clinical situation and progress in patients with infectious respiratory disorders. We consider that the immunoferon constitutes a coadjuvant therapy to bacterial immunotherapy. PMID- 1509988 TI - An investigation into the relationship between coal workers' pneumoconiosis and dust exposure in U.S. coal miners. AB - The National Study of Coal Workers' Pneumoconiosis (NSCWP) is a large, continuing epidemiologic study of the respiratory health of U.S. coal miners. By using information from the study, prevalence of coal workers' pneumoconiosis (CWP) was related to indexes of dust exposure obtained from research and compliance sampling data. Clear relationships between prevalences of both simple CWP and progressive massive fibrosis (PMF) and estimated dust exposure were seen. Additional effects independently associated with coal rank (% carbon) and age were also seen. Logistic model fitting indicated that between 2% and 12% of miners exposed to a 2-mg/m3 dust environment in bituminous coal mines would be expected to have Category 2 or greater CWP after a 40-yr working life; PMF would be expected for between 1.3% and 6.7%. The risks for anthracite miners appeared to be greater. There was a suggestion of a background level of abnormality, not associated with dust exposure, but increasing with age. Although there are certain weaknesses in the data used to derive these exposure estimates, the results are in general agreement with, but somewhat greater than, some recent findings for British coal miners. PMID- 1509987 TI - Wasp sting anaphylaxis as a cause of death: a case report. AB - A case of death after anaphylactic reaction to a vespid is reported. The antecedent of the patient, the RAST and the RAST-Inhibition results and the geographical distribution of the vespids indicate that the responsible species was "Polistes dominulus". The pathologic finding supported that the cause of the death was an anaphylactic reaction without coexistence of any previous cardiovascular disease or other coexisting agent that could precipitate the fatal outcome. PMID- 1509989 TI - A theoretical model for respirator cartridge service life for binary systems: application to acetone/styrene mixtures. AB - A theoretical model, developed previously to assess respirator cartridge service life, was applied to various acetone/styrene binary assault systems. Experimental data, collected for several binary mixtures differing only with respect to the concentration of each of the two compounds, were interpreted in terms of the model. Styrene concentrations varied from 228 to 1578 ppm; the range of acetone concentrations was 92-985 ppm. The specific influence of the compound assault concentrations on respirator cartridge service life was carefully characterized, as break-through curves were generated for both acetone and styrene for each of several different binary systems. Specifically, experimental data for each system were used to determine values of the following theoretical parameters: k'1, tau 1, k'2, tau 2, and Am. These parameters were employed with the theory to generate complete theoretical breakthrough curves and to determine the time-dependence of the weight of each compound adsorbed by the respirator cartridge carbon bed. An interesting phenomenon observed for the acetone/styrene systems was the displacement (from the carbon) of previously adsorbed acetone molecules by styrene molecules. Acetone breakthrough was observed first in each of the systems studied. Following the onset of this breakthrough, the acetone breakthrough concentration was enhanced by the displacement of acetone from the carbon bed by the adsorption of styrene. The theoretical model accurately predicts both this enhancement and the associated breakthrough characteristics of styrene. In addition, the theory is capable of predicting the ratio of the number of displaced acetone molecules to the corresponding number of displacing styrene molecules. For these studies, this ratio ranged from 0.3 to 0.7. The service life of respirator cartridges exposed to acetone/styrene mixtures depends on the assault concentration of each compound and is significantly influenced (shortened) by the displacement phenomenon. PMID- 1509990 TI - Pulmonary effects of inhaled zinc oxide in human subjects, guinea pigs, rats, and rabbits. AB - Occupational exposure to freshly formed zinc oxide (ZnO) particles (less than 1.0 micron aerodynamic diameter) produces a well-characterized response known as metal fume fever. An 8-hr threshold limit value (TLV) of 5 mg/m3 has been established to prevent adverse health effects because of exposure to ZnO fumes. Because animal toxicity studies have demonstrated pulmonary effects near the current TLV, the present study examined the time course and dose-response of the pulmonary injury produced by inhaled ZnO in guinea pigs, rats, rabbits, and human volunteers. The test animals were exposed to 0, 2.5, or 5.0 mg/m3 ZnO for up to 3 hr and their lungs lavaged. Both the lavage fluid and recovered cells were examined for evidence of inflammation or altered cell function. The lavage fluid from guinea pigs and rats exposed to 5 mg/m3 had significant increases in total cells, lactate dehydrogenase, beta-glucuronidase, and protein content. These changes were greatest 24 hr after exposure. Guinea pig alveolar macrophage function was depressed as evidenced by in vitro phagocytosis of opsonized latex beads. Significant changes in lavage fluid parameters were also observed in guinea pigs and rats exposed to 2.5 mg/m3 ZnO. In contrast, rabbits showed no increase in biochemical or cellular parameters following a 2-hr exposure to 5 mg/m3 ZnO. Differences in total lung burden of ZnO, as determined in additional animals by atomic absorption spectroscopy, appeared to account for the observed differences in species responses. Although the lungs of guinea pigs and rats retained approximately 20% and 12% of the inhaled dose, respectively, rabbits retained only 5%.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1509991 TI - Use of fluidizing bed aerosol generators to establish a dust mixture of two substances at a fixed ratio for inhalation toxicity studies. AB - A method was developed to use two fluidizing bed generators to deliver a mixture of 1 mg cobalt + 15 mg tungsten carbide/m3 to an inhalation exposure chamber with the output from the cobalt generator split to provide the same cobalt concentration to a cobalt-only chamber. To provide a more uniform delivery of material and to minimize the amount of starting dust needed, a subsystem that produced timed bursts of compressed air was used to prevent the accumulation of dust along the aerosol transport tubes. The addition of an electrostatic precipitator placed in the exhaust lines reduced the amount of dust delivered to the high-efficiency particulate air filters, thereby reducing the number of filter changes. PMID- 1509992 TI - Industrial hygiene and national health objectives for the year 2000. AB - Industrial hygiene can have a powerful effect on family, community, and environmental health in addition to its effect on occupational health. Contemporary industrial hygiene begins in the workplace, but its impact can spread and improve the health status of the nation in several ways. Thirteen objectives for industrial hygiene are presented in this report. Industrial hygienists should know what the objectives are, how the objectives are useful to their practice, and how they can help to achieve them to improve the health of Americans. PMID- 1509993 TI - Long-term safety and efficacy of flecainide in the treatment of supraventricular tachyarrhythmias: the United States experience. The Flecainide Supraventricular Tachyarrhythmia Investigators. AB - Information about long-term safety and effectiveness is important for appropriate use of antiarrhythmic drug therapy. We report the results of an open-label, long term (mean, 15 months) therapy extension for 66 patients with paroxysmal supraventricular tachycardia (PSVT) or atrial fibrillation (PAF) in whom short term therapy in 2 controlled studies was deemed beneficial by both patient and investigator. Follow-up was accomplished by clinic visits and telephone calls. Results indicated excellent ongoing tolerance and safety. Only 3 (5%) of 66 patients discontinued therapy due to possible noncardiac adverse effects. Only 5 (7.6%) discontinued therapy due to inadequate clinical response. Only 1 discontinuation was ascribed to a worsening arrhythmia (increased frequency of sustained PAF). In PSVT patients, 75% of months were arrhythmia free; in PAF patients, 64% of months were attack free. No clinically significant laboratory, electrocardiographic, or physical abnormalities were ascribed to flecainide. Thus, the long-term safety and efficacy profile of the drug for treatment of PSVT and PAF is encouraging. This promising clinical experience is relatively small and so should be reinforced by larger patient trials in the future. PMID- 1509994 TI - Long-term follow-up of patients with inducible supraventricular tachycardia treated with flecainide or propafenone: therapy guided by transesophageal electropharmacologic testing. AB - We report our experience with flecainide and propafenone therapy for inducible supraventricular tachycardias and paroxysmal supraventricular tachycardias due to atrioventricular (AV) nodal reentry or the Wolff-Parkinson-White syndrome. We performed an electropharmacologic test (ET) that consisted of first inducing a clinical arrhythmia by transesophageal atrial pacing (TAP) protocol. This was followed by intravenous drug administration and TAP reevaluation, either after acute intravenous administration or in oral steady-state. We used ET with flecainide and/or propafenone to study 2 groups of patients at least 3 years before the long-term clinical observation period. The first group was comprised of 58 patients with reciprocating tachycardias--due to AV node reentry in 17 (29.3%) and anomalous pathway in 41 (70.7%). Twelve (29.3%) of the latter had reciprocating tachycardias, 15 (36.6%) had atrial fibrillation, and 14 (34.2%) had both arrhythmias. During ET, flecainide was administered to 42 patients, and the ET was considered positive in 28 (66.7%). Propafenone was administered to 32 patients, with positive results in 15 (46.9%). In 15 patients, both flecainide and propafenone were tested, 8 receiving flecainide after a negative ET with propafenone, and 7 receiving propafenone after a negative ET with flecainide. In the first group, the ET was positive in 7 (87.5%), and in the second group, it was positive in 3 (42.9%). In a follow-up of 40.1 +/- 11 months, 38 (65.5%) patients had positive outcomes, 5 (8.6%) had to stop receiving the drugs because of side effects, 3 (5.2%) stopped because of inefficacy, and 12 (20.7%) dropped out.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1509995 TI - Flecainide in the Wolff-Parkinson-White syndrome. AB - The effects of flecainide on electrophysiologic parameters and arrhythmias in the Wolff-Parkinson-White syndrome were reviewed. Acute administration of flecainide blocks conduction across the accessory pathway in the anterograde direction in 40% and in the retrograde direction in 50% of cases and markedly prolongs refractoriness in the remaining cases. Flecainide has a lesser effect on refractoriness of the His-Purkinje system, atrium, ventricle, and atrioventricular node. Flecainide terminates atrioventricular tachycardia in greater than 80% of cases when given intravenously, and oral therapy prevents clinical recurrences in greater than 60% of cases, but may occasionally result in incessant tachycardia. Long-term efficacy is predicted by abolition of conduction across the accessory pathway or prevention of tachycardia induction at acute electrophysiologic testing. Concomitant administration of a beta-adrenoreceptor blocker results in greater long-term efficacy. Administered during preexcited atrial fibrillation, flecainide consistently slows the ventricular response and converts the majority of cases to sinus rhythm. Serious ventricular proarrhythmia is seen almost exclusively in patients with structural cardiac disease. Flecainide is a useful drug for the acute and chronic control of tachycardia in Wolff-Parkinson-White syndrome. PMID- 1509996 TI - Effects of flecainide on atrial electrophysiology in the Wolff-Parkinson-White syndrome. AB - The effects of intravenous flecainide and propafenone (2 mg/kg) administered in random order were compared in 16 patients with Wolff-Parkinson-White syndrome. Both agents prolonged significantly the anterograde refractory period of the pathway and caused complete anterograde block in the pathway in 5 patients. Atrial fibrillation was not inducible in 7 patients following both agents. Both drugs prolonged the minimum pre-excited RR interval, but this effect was significantly greater after flecainide than after propafenone. At a pacing cycle length of 500 msec, the atrial effective refractory period was unchanged after flecainide, but the atrial monophasic action potential duration, and the atrial monophasic action potential duration of the earliest inducible atrial beat were significantly increased. These results suggest that rate-dependent prolongation of atrial repolarization does not occur following clinical intravenous doses of flecainide. The prolongation of the repolarization of ectopic beats may prevent induction of atrial arrhythmias and may also have an important role in the termination of atrial fibrillation. PMID- 1509997 TI - Atrial fibrillation in the Wolff-Parkinson-White syndrome. AB - Atrial fibrillation in patients with Wolff-Parkinson-White (WPW) syndrome may lead to syncope, ventricular fibrillation, and sudden death. In a follow-up study of 241 patients with WPW syndrome in a relatively unselected population, 26 patients had documented atrial fibrillation (11%). These patients were followed up after 1-37 years (median 11 years; mean 15 years). During this period, 2 of 26 died suddenly. These 2 patients had the shortest RR interval during spontaneous atrial fibrillation (less than or equal to 220 msec), greater than or equal to 1 episodes of syncope, and a persistent delta wave in all available electrocardiograms. In comparison, sudden or tachycardia-related death was seen in 4 of the 241 patients. This difference is not statistically significant. Thus, atrial fibrillation of 26 patients with WPW syndrome was surprisingly well tolerated in our follow-up study with only 2 sudden deaths. PMID- 1509998 TI - Flecainide acetate in the prevention of paroxysmal atrial fibrillation: a nine month follow-up of more than 500 patients. AB - In order to assess efficacy, safety, and long-term tolerance of flecainide for the prevention of paroxysmal atrial fibrillation (PAF), 944 patients (555 male) were enrolled in an open multicenter study. All patients had had greater than or equal to 1 episodes of atrial fibrillation and were in sinus rhythm at the time of entry. The mean age was 65.3 +/- 11 years, and 43% of patients had no detectable heart disease. The mean daily dose of flecainide was 190 +/- 34 mg. Clinical examination, electrocardiogram (ECG) and 24-hour Holter monitoring were performed at entry into the study and on months 3, 6, and 9. Of the patients, 189 were lost to follow-up. Of the remaining 755 patients, 562 (74%) continued the treatment during the 9-month period and 193 (26%) dropped out. A total of 84 adverse effects were reported in 7.6% enrolled patients and in 9% of patients during follow-up, with treatment interruption in 50% of the cases. There were only 3 minor cardiovascular side effects, all leading to treatment discontinuation. No deaths in patients with recurrent PAF and no proarrhythmic events were reported. Flecainide appears to be effective in preventing PAF, with 65% of patients being arrhythmia-free after 9 months of treatment at a mean daily dose of 200 mg. Side effects were common, but clinically significant adverse events were infrequent. PMID- 1509999 TI - Efficacy of flecainide for the reversion of acute onset atrial fibrillation. AB - The efficacy and safety of intravenous flecainide to convert recent-onset atrial fibrillation (AF) (present for greater than or equal to 30 minutes and less than or equal to 72 hours and a ventricular response greater than or equal to 120 beats/min) was investigated. A total of 102 patients without severe heart or circulatory failure were randomized to receive either intravenous flecainide (2 mg/kg, maximum dose 150 mg; 51 patients) or placebo (51 patients) in a double blind trial. Digoxin (500 micrograms intravenously) was administered to all patients who had not previously been receiving digoxin. The electrocardiogram was monitored continuously during the study. In 29 (57%) patients stable sinus rhythm was restored within 1 hour after flecainide and in only 7 (14%) given placebo (chi square 18.9; p = 0.000013; odds ratio 8.3; 95% confidence interval 2.9 24.8). Reversion to sinus rhythm within 1 hour after starting the trial medication was considered a pretrial end point and likely to be due to a drug effect. At the end of the 6-hour monitoring period, 34 patients (67%) in the flecainide group were in sinus rhythm whereas only 18 (35%) in the placebo group had reverted (chi square 8.83, p = 0.003; odds ratio 3.67; 95% confidence interval 1.5-9.1). Significant hypotension, although short lived, was more common in the flecainide group. One patient given flecainide developed torsades de pointes and was successfully electrically cardioverted. Flecainide is useful for the management of recent-onset AF both for control of the ventricular response and conversion to sinus rhythm.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1510000 TI - Acute pharmacologic conversion of atrial fibrillation and flutter: the role of flecainide, propafenone, and verapamil. AB - Efficacy and safety of intravenous flecainide (2 mg/kg body weight in 10 minutes), verapamil (10 mg in 1 minute), and propafenone (2 mg/kg body weight in 10 minutes) were investigated in 90 consecutive patients with atrial fibrillation (AF) or flutter (AFL). In the first 40 patients, flecainide and verapamil were evaluated; in the second 50 patients, flecainide and propafenone were compared, both in a single-blind randomized study design. The primary end point was sinus rhythm occurring within 1 hour after start of infusion. Sinus rhythm was attained in 32 of 37 patients (86%) with AF treated with flecainide and in 11 of 20 patients (55%) with AF treated with propafenone. In recent onset AF (less than or equal to 24 hours) conversion rates were 24 of 25 patients (96%) in the flecainide group and 8 of 14 patients (57%) in the propafenone group (p less than 0.05). Conversion of AFL occurred in only 1 of 8 patients (13%) in the flecainide treated patients and in 2 of 5 patients (40%) treated with propafenone (difference not significant). Verapamil was almost ineffective, since only 1 of 20 patients (5%) responded within 1 hour. Time to conversion was 21 +/- 17 minutes in the flecainide group and 16 +/- 10 minutes in the propafenone group. QRS widening occurred in flecainide-treated patients (83 +/- 15 to 99 +/- 20 msec; p less than 0.001), but not after propafenone (83 +/- 11 to 86 +/- 12 msec). Significantly higher plasma levels were found in patients with conversion within 1 hour using propafenone.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1510001 TI - Flecainide in quinidine-resistant atrial fibrillation. AB - Flecainide (100 mg twice daily) was used for prevention of paroxysmal atrial fibrillation (PAF) in 52 patients with frequent symptomatic attacks that were resistant or intolerant to quinidine (600-900 mg/day). Underlying heart disease was present in only 8 cases and left ventricular ejection fraction was always greater than 30%. No patient had had a myocardial infarction. Vagally induced PAF was clinically documented in 35 patients. Amiodarone, previously used and ineffective, was combined with flecainide in 33 patients. After 1-5.8 years of follow-up, complete disappearance of PAF was observed in 38 patients (73%). The success rate was slightly higher in patients with vagally induced PAF (p = 0.07). Extracardiac side effects necessitated withdrawal in only 3 cases. Permanent pacemaker was needed in 7 patients on amiodarone and flecainide because of excessive sinus bradycardia. Two patients, with previously documented atrial flutter, experienced presyncopal episodes of atrial flutter with 1:1 atrioventricular (AV) conduction and wide QRS complex. No death occurred during the follow-up. In this series, quinidine proved to be unsuccessful in 46 patients and it was withdrawn in 6. We concluded that flecainide is efficient and well tolerated for long-term prevention of PAF in patients resistant to quinidine. The possibility of 1:1 AV conduction during atrial flutter may suggest the use of verapamil or beta blockers in combination with flecainide in patients with previously documented atrial flutter. PMID- 1510002 TI - Pharmacologic treatment of supraventricular tachycardia: the German experience. AB - Tachyarrhythmias that originate above the bifurcation of the bundle of His or in tissue proximal to it are classified as supraventricular tachyarrhythmias (SVTs). Primary treatment of SVT tries to influence the underlying disease. Symptomatic therapy is subdivided into drug therapy, electrotherapeutic tools (e.g., antitachycardia pacemakers, catheter ablation), and antiarrhythmic surgery. Antiarrhythmic agents that slow conduction and suppress premature beats are efficient for emergency and long-term treatment of SVTs. We evaluated some of the most relevant antiarrhythmic drugs in SVT, including propafenone, diprafenone, cibenzoline, sotalol, and diltiazem; in addition, usage and efficacy of quinidine/verapamil, disopyramide, amiodarone, ajmaline, adenosine, and flecainide are summarized. In 1990, the case load of supraventricular arrhythmias per physician in Germany was more than 30 patients seen per month. About 50% of them were treated with drug therapy; i.e., approximately 17 patients were treated with antiarrhythmic drugs per month per physician for supraventricular arrhythmias. The most important antiarrhythmic agents used in Germany are propafenone (40%), combination of quinidine and verapamil (23%), sotalol (12%), disopyramide (6%), flecainide (6%), and other (13%). PMID- 1510003 TI - Performance status and outcome after coronary artery bypass grafting in persons aged 80 to 93 years. AB - Although coronary artery bypass grafting (CABG) effectively eliminates or diminishes symptoms of myocardial ischemia, the overall performance status and functional outcome in elderly patients undergoing CABG is poorly documented. Therefore, 86 consecutive patients aged 80 to 93 years undergoing isolated CABG were reviewed. Preoperative, intraoperative, and postoperative characteristics and pre- and postoperative performance status (Karnofsky score) were examined. Forty patients (47%) were women, and most patients had highly symptomatic coronary artery disease with class III or IV angina in 94% and unstable angina in 90%. Significant co-morbid disease was present in 49% of patients, and cardiac catheterization revealed left main or 3-vessel disease in 74% of patients. The rate of significant in-hospital complications was 29%, with infection in 14%, stroke in 9%, and respiratory failure in 8% being most frequent. Median performance status (Karnofsky score) improved from 20 to 70% (p = 0.0001) with 89% of hospital survivors being discharged home. Factors associated with failure to achieve a successful functional outcome at discharge were presence of 1 or more preoperative co-morbid conditions (p = 0.048), preoperative myocardial infarction within 7 days of operation (p less than 0.01), and postoperative low cardiac output (p less than 0.01). Survival at 30 days, 6 months, and 3 years were 90, 78, and 64%, respectively. These data demonstrate that CABG can be offered to selected elderly patients with acceptable morbidity and mortality, marked improvement in performance status, and an acceptable quality of life. PMID- 1510004 TI - Exercise echocardiography after coronary artery bypass grafting. AB - Exercise echocardiography was used to assess the adequacy of regional myocardial perfusion in 125 patients who had undergone coronary artery bypass grafting. There were 108 men and 17 women (mean age 65 years) evaluated from 6 weeks to 16 years (mean 7 years) after surgery. Resting parasternal long- and short-axis and apical 4- and 2-chamber echocardiograms were recorded, digitized and stored. Maximal, symptom-limited upright treadmill exercise was then performed with continuous electrocardiographic monitoring. Repeat echocardiographic imaging and digitization were repeated within 1 minute of exercise termination. Resting and postexercise digitized echocardiograms were compared. A normal regional wall motion response to exercise consisted of improved segmental contraction and was used to predict uncompromised regional vascular supply. Unimproved or worsened segmental contraction after exercise was abnormal and was used as a predictor of regional vascular insufficiency. All patients underwent cardiac catheterization within 1 month after exercise testing. Regional coronary insufficiency was considered to exist when a segment's major vascular conduit exhibited greater than or equal to 50% luminal diameter reduction. Compared with the simultaneously acquired stress electrocardiogram, exercise echocardiography had superior sensitivity (98 vs 41%), specificity (92 vs 67%), positive predictive value (99 vs 91%), and negative predictive value (86 vs 12%) (p less than 0.001, 0.1, 0.01 and less than 0.001, respectively). In addition, exercise echocardiography correlated closely with the extent and regional distribution of compromised vascular supply. Exercise echocardiography is a highly sensitive, specific and accurate screening test for abnormal global and regional myocardial vascular supply in patients who have undergone coronary artery bypass grafting. PMID- 1510005 TI - Normalization of impaired response of platelets to prostaglandin E1/I2 and synthesis of prostacyclin by insulin in unstable angina pectoris and in acute myocardial infarction. AB - The minimal inhibitory concentration of prostaglandin E1 (used as a probe for prostacyclin [PGI2]) needed to inhibit platelet aggregation (36 +/- 16 nM) in normal volunteers (n = 40) increased (64 +/- 30 nM) in patients (n = 46) with acute coronary artery disease. Bolus injection of insulin in 20 patients, 0.1 U/kg body weight 4 times a day (every 6 hours) for 7 days decreased the minimal inhibitory concentration of prostaglandin E1 from 64 +/- 30 to 26 +/- 12 nM (p less than 0.001). Twenty other patients who received only saline solution had no decrease in minimal inhibitory concentration of the prostanoid. The bolus injection of insulin also increased the plasma level of PGI2 (9 +/- 2 pM) two fold in these patients (28 +/- 10 pM). Administration of aspirin inhibited the insulin-induced increase of plasma prostanoid level. Patients in the placebo group had no increase in plasma PGI2 level. The bolus injection of insulin administered only once to another group of patients (n = 6) demonstrated that the hormonal effects were maximally increased within an hour of insulin administration, and were directly related to the increased insulin level in plasma. These results indicated the feasibility of using physiologic quantities of insulin for controlling of platelet aggregation through resensitization of platelet response to prostaglandin and increased synthesis of PGI2 in vivo in acute coronary artery disease. PMID- 1510007 TI - Lack of effect of midazolam on inducibility of arrhythmias at electrophysiologic study. AB - Midazolam has several advantages over diazepam as a sedative agent in electrophysiologic studies, but its electrophysiologic effects in humans are unknown. Therefore, its effects were studied in 20 patients undergoing electrophysiologic studies. Electrophysiologic variables were measured before and after administration of intravenous midazolam (5 mg). There were no significant changes in the electrophysiologic variables, apart from a minor decrease in sinus cycle length (711 +/- 124 vs 647 +/- 91 ms; p = 0.005). Ease of inducibility of reentrant tachycardia was not significantly altered by midazolam, and tachycardia remained inducible in all patients. The drug was well-tolerated with no significant side effects, apart from a minor reduction (mean 18 mm Hg) in blood pressure (p less than 0.001). Good amnesic effect was achieved in 16 patients, and most patients preferred it to oral diazepam for sedation during the procedure. It is concluded that midazolam can be used safely in patients undergoing electrophysiologic studies without significantly interfering with electrophysiologic variables or the inducibility of reentrant tachycardias. PMID- 1510006 TI - Acute conversion of paroxysmal supraventricular tachycardia with intravenous diltiazem. IV Diltiazem Study Group. AB - Diltiazem has electrophysiologic effects similar to those of verapamil. Its efficacy and safety in 4 doses for treatment of induced supraventricular tachycardia (SVT) were examined and compared with those of placebo in 87 patients (25 with atrioventricular [AV] nodal reentry tachycardia, 60 with AV reentry associated with an accessory AV connection, and 2 with atrial tachycardia). Conversion to sinus rhythm occurred in 4 of 14 patients (29%) with 0.05 mg/kg of diltiazem, 16 of 19 (84%) with 0.15 mg/kg, 13 of 13 (100%) with 0.25 mg/kg, and 14 of 17 (82%) with 0.45 mg/kg compared with 6 of 24 (25%) treated with placebo. Conversion rates in groups receiving doses of 0.15 to 0.45 mg/kg of diltiazem were superior to that in the placebo group (p less than 0.001). Time to conversion was 3.0 +/- 2.6 minutes in responding diltiazem patients compared with 5.9 +/- 6.1 minutes in responding control patients. Diltiazem administration resulted in significant lengthening of SVT cycle length, AH interval, and AV nodal effective refractory period and block cycle length. The most frequent adverse response to diltiazem was hypotension (7 of 63 patients); however, only 4 patients had symptoms related to hypotension. Thus, intravenous diltiazem in doses of 0.15, 0.25 and 0.45 mg/kg is an effective and safe treatment for the acute management of SVT. PMID- 1510008 TI - Reproducibility of a symptomatic response to upright tilt in young patients with unexplained syncope. AB - Serial upright tilt testing has been advocated as a possible therapeutic end point in treating patients with recurrent syncope, but the reproducibility of such testing has not been well-established in the absence of therapy. In 21 patients with recurrent syncope and a symptomatic response to upright tilt testing, tilt was repeated following a 25- to 30-minute recovery. Syncope or presyncope was reproduced in 14 of 21 patients on repeat tilt; 4 of 21 patients experienced milder symptoms, and 3 of 21 patients remained entirely asymptomatic on repeat tilt. The pattern of physiologic response was different during initial and repeat tilt in 7 of the 21 patients. Blood pressure and heart rate (before and during symptoms) were similar for the group on initial and repeat tilt. The abnormal physiologic response and associated symptoms elicited during upright tilt testing for unexplained syncope can be reproduced on immediate repeat tilt testing in most patients. However, the frequently attenuated response during repeat testing may limit its use as a therapeutic end point in individual patients. PMID- 1510009 TI - Circadian rhythm of heart rate variability in survivors of cardiac arrest. AB - Reduced heart rate (HR) variability is associated with increased risk of cardiac arrest in patients with coronary artery disease. In this study, the power spectral components of HR variability and their circadian pattern in 22 survivors of out-of-hospital cardiac arrest not associated with acute myocardial infarction were compared with those of 22 control patients matched with respect to age, sex, previous myocardial infarction, ejection fraction and number of diseased coronary arteries. Survivors of cardiac arrest had significantly lower 24-hour average standard deviation of RR intervals than control patients (29 +/- 10 vs 51 +/- 15 ms, p less than 0.001), and the 24-hour mean high frequency spectral area was also lower in survivors of cardiac arrest than in control patients (13 +/- 7 ms2 x 10 vs 28 +/- 14 ms2 x 10, p less than 0.01). In a single cosinor analysis, a significant circadian rhythm of HR variability was observed in both groups with the acrophase of standard deviation of RR intervals and high-frequency spectral area occurring between 3 and 6 A.M. which was followed by an abrupt decrease in HR variability after arousal. The amplitude of the circadian rhythm of HR variability did not differ between the groups. Thus, HR variability is reduced in survivors of cardiac arrest but its circadian rhythm is maintained so that a very low HR variability is observed in the morning after awakening, corresponding to the time period at which the incidence of sudden cardiac death is highest. PMID- 1510010 TI - Use of telemetry functions in the assessment of implanted antitachycardia device efficacy. AB - Twenty patients (aged 50 +/- 21 years and mean left ventricular ejection fraction 37 +/- 17%) with recurrent ventricular arrhythmias were treated with an investigational, implantable combined antitachycardia-pacing cardioverter defibrillator. The device's telemetry capabilities include both stored (1-second snapshots) and real-time display of endocardial and device-circuit signals. The device can store these before, during and after up to 50 tachycardia and antitachycardia pacing episodes. All stored events are indexed to a 24-hour internal clock. During 10.1 +/- 5.1 months of follow-up, the device was used in 11 of 20 patients. In the entire group, antitachycardia pacing was activated on 44 +/- 14 occasions per patient (total 874) and shock delivery occurred on 8 +/- 14 occasions per patient (total 156). Reconstruction by stored telemetry of all device-therapy episodes was possible. Twenty-six percent of all shocks delivered were not appropriate and were due to atrial arrhythmias in 2 patients and dysfunction of the sensing lead in 3. The absence of a relation between symptoms and appropriate shock delivery was documented in 1 patient. Antitachycardia pace acceleration occurred in 5.3% of cases; 7% of attempts at pacing were unsuccessful and needed shock therapy. It is concluded that the enhanced telemetry available in newer antitachycardia devices enables more accurate assessment of device use and enhances diagnosis of inappropriate therapy delivery. PMID- 1510011 TI - Exercise hyperventilation chronic congestive heart failure, and its relation to functional capacity and hemodynamics. AB - The ventilatory response to exercise was evaluated in 26 normal sedentary men and 68 patients with chronic heart failure using the slope of the relation between minute ventilation (VE) and carbon dioxide production (VCO2). All subjects underwent maximal upright bicycle cardiopulmonary exercise testing; 33 patients also underwent right-sided cardiac catheterization. The slope of VE/VCO2 was calculated by linear regression analysis using data from all the exercise tests and the first 60% of exercise duration; a high correlation was seen between these results (r = 0.83; p less than 0.001). The slope of VE/VCO2 was significantly, though weakly, related to peak exercise work load, oxygen consumption and ventilatory threshold (r = -0.49, -0.56 and -0.49, respectively), several peak exercise hemodynamic parameters and peak exercise dead space/tidal volume ratio (r = 0.70). With use of multivariate analysis, the only independent determinants of the slope were peak exercise dead space/tidal volume ratio and cardiac index. Thus, in patients with heart failure, exercise hyperventilation can contribute to the impairment of functional capacity and can be considered a compensatory response to abnormal hemodynamics and lung blood distribution in order to keep blood gas concentrations normal. PMID- 1510013 TI - Immediate effects of percutaneous transvenous mitral commissurotomy on pulmonary hemodynamics at rest and during exercise in mitral stenosis. AB - Hemodynamics were evaluated during exercise in 33 patients with mitral stenosis who underwent percutaneous transvenous mitral commissurotomy (PTMC). PTMC was performed using an Inoue balloon. Each patient underwent a supine ergometer exercise test before and on the day after PTMC. Ergometer work load was started at 20 W and increased in increments of 20 W at 3-minute intervals until terminated by the patient's fatigue or shortness of breath. Mitral valve area increased by 0.8 +/- 0.4 cm2 (1.1 +/- 0.3 to 1.9 +/- 0.4 cm2, p less than 0.001). Mean mitral pressure gradient decreased (12 +/- 5 to 6 +/- 2 mm Hg, p less than 0.001). Pulmonary arterial pressure significantly decreased and the cardiac index significantly increased both at rest and during exercise after PTMC. Before PTMC, the increases in pulmonary arterial pressure, total pulmonary resistance and pulmonary arteriolar resistance during exercise were greater in patients with a mitral valve area less than 1.0 cm2 than in patients with an area greater than or equal to 1.0 cm2. After PTMC, total pulmonary resistance still increased during exercise. However, pulmonary arteriolar resistance did not change during exercise in patients with a mitral valve area greater than or equal to 1.5 cm2, whereas it increased in patients with an area less than 1.5 cm2. An enlarged mitral valve area greater than or equal to 1.5 cm2, which may prevent pulmonary vasoconstriction and permits a greater increase in pulmonary blood flow during exercise, is considered a good result immediately after PTMC. PMID- 1510012 TI - Exclusion of coronary artery disease by exercise thallium-201 tomography in patients with aortic valve stenosis. AB - In many patients with valvular aortic stenosis (AS), management decisions may be possible without invasive studies if coexistent coronary artery disease (CAD) can be ruled out noninvasively. The use of thallium-201 single-photon emission computed tomography to the exclusion of CAD was studied in 44 patients aged 41 to 78 years with AS. In addition to cardiac catheterization and selective coronary angiography, patients underwent a cardiac ultrasound study and thallium-201 myocardial perfusion imaging at rest and after bicycle ergometer exercise. Two thirds of the patients had critical AS (valve area index less than or equal to 0.5 cm2/m2) but none had left ventricular systolic dysfunction. Twenty-one patients had angiographically significant CAD (greater than or equal to 50% diameter stenosis in greater than or equal to 1 coronary artery), whereas 23 had either a fully normal angiogram (n = 17) or mild (less than 50%) stenoses (n = 6). Each patient with significant CAD had an abnormal thallium-201 tomogram, either a strictly segmental perfusion defect (n = 19), or a patchy nonsegmental abnormality (n = 2); however, 10 of 23 patients free of significant CAD had similar results. Thus, the sensitivity and specificity of an abnormal scintigram were 100 and 57%, respectively. If only segmental perfusion defects typical of CAD had been considered abnormal, then the sensitivity of the test would have been 90% and the specificity 70%. Patients with false abnormal scintigrams had more severe AS and more angiographically nonsignificant CAD than those with true normal findings.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1510014 TI - Comparison of the cardiotoxicity of ethanol in women versus men. AB - Subclinical left ventricular (LV) dysfunction is a common occurrence in alcoholic men but has been claimed to be absent or very rare in alcoholic women. M-mode echocardiography was performed to study LV size, mass and systolic function, and Doppler ultrasound to study LV filling in 14 chronic female alcoholics aged 24 to 48 years and in 2 age-matched control groups consisting of 17 healthy women and 22 alcoholic men. Compared with healthy women, female alcoholics had no differences in heart rate or blood pressure but a shorter LV end-diastolic diameter (mean +/- standard deviation, 46 +/- 4 vs 48 +/- 3 mm, p less than 0.05), lower fractional shortening (31 +/- 6 vs 34 +/- 3%, p less than 0.05), increased wall thickness to radius ratio (0.43 +/- 0.08 vs 0.37 +/- 0.05, p less than 0.05), reduced peak early diastolic transmitral velocity (45 +/- 11 vs 68 +/ 7 cm/s, p less than 0.001), reduced deceleration of the early diastolic velocity (-274 +/- 69 vs -572 +/- 107 cm/s2, p less than 0.001), and an increased atrial filling fraction (35 +/- 12 vs 27 +/- 5%, p less than 0.05). Although alcoholic men had a longer duration of heavy drinking than alcoholic women (median 19 vs 5 years, p less than 0.001), and a higher systolic blood pressure (140 +/- 17 vs 120 +/- 17 mm Hg, p less than 0.001), there were no statistically significant differences between the sexes either in LV diameters, wall thickness or mass normalized to body area, or in indexes of systolic or diastolic LV function.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1510015 TI - Altered cardiac hemodynamic and electrical state in normal sinus rhythm after chronic dual-chamber pacing for relief of left ventricular outflow obstruction in hypertrophic cardiomyopathy. AB - Dual-chamber (DDD) pacing relieves left ventricular (LV) outflow tract obstruction in patients with hypertrophic cardiomyopathy. The reduction in LV outflow gradient persists in some patients after cessation of pacing. Twelve-lead and signal-averaged electrocardiograms were obtained before and after 12 weeks of DDD pacing in 18 patients with obstructive hypertrophic cardiomyopathy to determine whether the altered hemodynamic state after chronic pacing is accompanied by electrical changes. Hemodynamic studies were performed at baseline and at follow-up. Signal-averaged electro-cardiograms were obtained using a Corazonix Predictor and bidirectional filters at 25 Hz to a noise level of less than 0.5 microV. At follow-up, LV outflow tract gradients were reduced significantly during DDD pacing and with cessation of pacing in sinus rhythm by 56 +/- 10 and 47 +/- 10 mm Hg, respectively (p less than 0.001). There was no simple relation between changes in LV outflow tract gradient and in the electrocardiogram. For example, amplitude of the R wave in V5,6 was reduced by greater than or equal to 0.5 mv in 4 patients, unchanged in 12 and increased in 2. Similarly, the S wave in leads V1,2 was reduced in 7 patients, unchanged in 7 and increased in 4. The T wave became more negative (greater than or equal to 0.1 mv) in leads II, III, aVF and V5,6 in 13 patients and more positive in leads I and aVL in 12.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1510016 TI - Long-term follow-up of patients undergoing myotomy/myectomy for obstructive hypertrophic cardiomyopathy. AB - The long-term results of patients undergoing myotomy/myectomy of the ventricular septum for obstructive hypertrophic cardiomyopathy are documented in 31 patients (15 women, 16 men, age range 21 to 80 years [mean 55]) with mean New York Heart Association functional class III to IV congestive heart failure, who underwent radical myotomy/myectomy at the Brigham and Women's Hospital from 1972 to 1991. Preoperative gradients by catheterization or echocardiography ranged from 26 to 240 mm Hg (average 96). There were no operative deaths. Two patients developed early postoperative complete heart block requiring a transvenous pacemaker. Clinical follow-up was 1 to 14 years (mean 6.5). All surviving patients were restudied by echocardiography and clinical examination. The mean postoperative functional class was II. Postoperative gradients ranged from 0 to 30 mm Hg (mean 4.5) (p less than 0.001 compared with preoperative values). There were 5 late deaths (low cardiac output in 2, stroke in 2, and acute respiratory failure in 1); 4 of 5 deaths occurred in patients with concomitant coronary artery disease. Survival at 10 years was 86 +/- 9%. There were no reoperations for subaortic obstruction. PMID- 1510017 TI - 1,000 consecutive children with a cardiac malformation with 26- to 37-year follow up. AB - The current status of 997 of 1,000 consecutive children with a cardiac malformation initially evaluated between 1952 and 1963 was determined. Of the 1000, 285 have died and the survivors have been followed up for periods of 26 to 37 years. Six hundred thirty-two are in excellent or good clinical condition, being asymptomatic and without planned need for further treatment. The other 80 have significant abnormalities, although 63 of these have few symptoms. Infective endocarditis occurred in 12 of 10,000 susceptible patient-years, with a lower rate in the past decade. Only 22 of the survivors are currently receiving cardiac medication. These data are derived from a group of patients initially seen during a period of time that cardiac surgery was being developed for congenital heart disease. Thus, the outlook should be even better for children who are currently undergoing treatment. PMID- 1510018 TI - Diagnosis of patent foramen ovale by transesophageal echocardiography and association with cerebral and peripheral embolic events. AB - This study compares the value of transthoracic (TTE) and transesophageal (TEE) color Doppler and contrast echocardiography for detecting a patent foramen ovale (PFO). A total of 238 patients were studied: 74 patients with a history of otherwise unexplained ischemic stroke, transient cerebral ischemic attacks or peripheral embolic events (group A), 48 with a history of similar episodes explained by other cardiac abnormalities (group B), and 116 with no embolic events (group C). A PFO was detected by contrast TEE in 50 of 238 patients (21%) compared with 45 patients (19%) by color Doppler TTE. In a subgroup of 198 patients, TEE results could be compared with TTE findings. No patient had a PFO identified by color Doppler TTE. Contrast TTE detected a PFO in 15 patients (8%) compared with contrast TEE which demonstrated a PFO in 44 of 198 patients (22%) (p less than 0.001). Prevalence of PFO by TEE was 22, 21 and 22% in groups A, B and C, respectively. A PFO was present in 50% of patients aged less than 40 years and otherwise unexplained ischemic stroke; this percentage was higher (p less than 0.05) than corresponding values found in all other groups. Thus, contrast and color Doppler TEE are significantly superior to TTE for detecting PFO. The prevalence of PFO is significantly increased in young adults with otherwise unexplained ischemic stroke. PMID- 1510019 TI - Hyperventilation syndrome and the assessment of treatment for functional cardiac symptoms. AB - Three methods of breathing retraining (guided breathing retraining, guided breathing retraining with physiologic monitoring of thoracic and abdominal movement plus peripheral temperature, and guided breathing retraining with physiologic monitoring of thoracic and abdominal movement, peripheral temperature and end-tidal carbon dioxide) were compared with a no-treatment control group to determine the effectiveness of breathing retraining on modifying respiratory physiology and reducing functional cardiac symptoms in subjects with signs associated with hyperventilation syndrome. Of 41 subjects studied, 16 were diagnosed with mitral valve prolapse. Results demonstrated that all 3 methods of breathing retraining were equally effective in modifying respiratory physiology and reducing the frequency of functional cardiac symptoms. Results determined that respiratory rate and subject's perception that training had generalized were the best predictors of treatment success. Furthermore, it was found that subjects with mitral valve prolapse responded as well to treatment as did those without prolapse. PMID- 1510021 TI - Association between residual mitral regurgitation and left ventricular outflow obstruction after Carpentier ring mitral annuloplasty. PMID- 1510020 TI - Percutaneous pericardial catheter drainage in childhood. AB - The clinical course of 41 consecutive pediatric patients (mean age 7.6 +/- 5.8 years, weight 27 +/- 22 kg) who underwent percutaneous pericardial drain placement during a 3-year period were reviewed. The most common diagnoses were malignancy (20%), postpericardiotomy syndrome (17%), aseptic pericarditis (12%), and patients recovering from a Fontan type of operation (12%). Indications for drainage included increasing effusion size determined by 2-dimensional echocardiogram (48%), clinical deterioration (33%) and echocardiographic evidence of hemodynamic compromise (12%). Only 3 (7%) patients had clinical evidence of cardiac tamponade. Drainage catheter placement was accomplished percutaneously from the subxiphoid approach. Insertion was successful in all but 1 patient (98%) and successful evacuation of the pericardial space was achieved in 93% of patients. There was 1 death in a critically ill 2-week-old infant and 4 complications, 3 of which occurred in patients aged less than 2 years. Drainage catheters remained in position from 1 to 18 days (mean 3 +/- 3 days) with no late complications. There were 3 instances (7%) of drainage catheter occlusion. These data support the notion that placement of a percutaneous pericardial catheter is safe and effective in providing definitive drainage of the pericardial space in the pediatric age group. Children younger than age 2 years may be at increased risk for complications. PMID- 1510022 TI - Aortic distensibility in children with the Marfan syndrome. PMID- 1510023 TI - Cardiac dysrhythmias before and after balloon aortic valvuloplasty in children. PMID- 1510024 TI - Histopathologic and angiographic analysis of coronary artery morphology six months after triple artery angioplasty. PMID- 1510025 TI - Successful treatment of medically refractory ventricular fibrillation with emergency cardiopulmonary bypass in an adolescent with corrected complex congenital heart disease. PMID- 1510027 TI - Can fine-needle aspiration replace open biopsy in the diagnosis of palpable breast lesions? PMID- 1510026 TI - Intrapericardial pheochromocytoma. PMID- 1510028 TI - Clarity in communication. PMID- 1510029 TI - Undertransfusion. PMID- 1510030 TI - Breast carcinoma simulating fibroadenoma or fibrocystic change by fine-needle aspiration. A study of 16 cases. AB - The cytologic features of fine-needle aspiration specimens from 16 breast carcinomas that closely simulated benign lesions were analyzed and compared to smears from fibroadenomas and fibrocystic change. No combination of features was found that accurately separated all benign and malignant cases. Many nuclei with discernible small nucleoli in smears with many single bipolar nuclei indicated a benign lesion, whereas nuclear hyperchromasia indicated a malignant one. PMID- 1510031 TI - Sialosyl-Tn antigen. Its distribution in normal human tissues and expression in adenocarcinomas. AB - In normal adult human tissues, sialosyl-Tn antigen, detected by monoclonal antibody TKH2, was uniformly found in the bronchus, uterus, salivary gland, palatine tonsil, testis, stomach, duodenum, and capillary endothelium of several organs. It was also sporadically found in the small intestine, appendix, colorectum, gallbladder, urinary bladder, skin, and esophagus. The antigen was absent in the other organs. Even in the organs showing positive findings, the antigen was observed only in the limited areas. In contrast, sialosyl-Tn antigen was expressed in a large number of adenocarcinomas in many kinds of organs. It was expressed in more than one half the adenocarcinomas of the pancreas, ovary, uterus, stomach, colorectum, and gallbladder, but not in hepatocellular carcinomas, renal cell carcinomas, and papillary carcinomas of the thyroid gland. Sialosyl-Tn antigen expression also was observed in intestinal metaplasia of the stomach and in transitional mucosa adjacent to the colorectal carcinoma, which are considered to be cancer-related lesions. These results indicate that sialosyl Tn antigen is a useful tumor marker, especially in adenocarcinomas of the mucin producing organs, and suggest that the regulation of sialosyl-Tn antigen synthesis in adenocarcinomas is different from that in normal tissues. PMID- 1510032 TI - Content and design of laboratory report forms for human immunodeficiency virus type 1 antibody testing. AB - In a pilot study involving proficiency testing for human immunodeficiency virus, markedly diverse and potentially confusing test report forms were encountered among participating laboratories. Therefore, a comprehensive study of human immunodeficiency virus type 1 report forms was conducted from state-licensed testing laboratories in California. Participants analyzed three serum samples of known human immunodeficiency virus type 1 antibody reactivity and reported their results on forms that they would normally submit to clinicians. Report forms from 84 laboratories were evaluated for content, design, and clarity. Differences were found among commercial, hospital, and public health laboratories. The significance of these findings is discussed. This technique also may be applied to evaluate laboratory report form design and content for other diagnostic test results. PMID- 1510033 TI - Acute megakaryoblastic leukemia in infants with t(1;22)(p13;q13) abnormality. AB - Six infants with acute megakaryoblastic leukemia and a translocation (1;22)(p13;q13) were studied. There were five female infants and one male infant, and the age at initial examination varied from 0.8 to 6.5 months (median, 2.3 months). All the patients had hepatosplenomegaly and anemia (6 to 8.3 g/dL), and four patients had thrombocytopenia (9,000 to 63,000/mm3). The bone marrow showed prominent fibrosis in five cases and reticulin fibrosis in one patient at presentation. Crush artifact often made the histologic sections difficult to interpret, but typical megakaryoblasts could be identified in the smears. Biopsy specimens of the liver and lymph node were suggestive of a nonhematopoietic malignant condition because of the cohesiveness of the tumor cells, stromal fibrosis, and the prominent sinusoidal and vascular pattern of infiltration. Immunophenotyping of peripheral blood mononuclear cells was helpful in identifying the blasts as belonging to the megakaryoblastic lineage. Using a panel of mononclonal antibodies, it was also possible to confirm the nature of the infiltration in paraffin sections and to differentiate it from other childhood small round cell tumors, especially neuroblastoma in paraffin sections (typical staining pattern: CD45-, CD43+, vW Factor, Ulex europeus I+, CD20-, CD45RO-, synaptophysin-, chromogranin-, cytokeratin-, desmin-). This special type of infantile acute leukemia can be recognized with confidence if one is aware of its clinical features, peculiar pathologic characteristics, the morphologic features and immunophenotype of the megakaryoblasts, and the unique cytogenetic abnormality. PMID- 1510034 TI - Dysplastic megakaryopoiesis with thrombocytopenia and chromosomal aberration. AB - A case of isolated thrombocytopenia with decreased platelet production and abnormal megakaryopoiesis is described. In the bone marrow, a chromosomally aberrant clone, 45,XX,-11,-18,+der (11;18)(11q13;18p11), was found. These findings indicate a myelodysplastic nature of the abnormal thrombocytopoiesis. The described case demonstrates the value of a bone marrow examination including histopathology with immunologic techniques to evaluate the megakaryopoiesis in thrombocytopenia and the interest of cytogenetic studies not only in instances with overt hematologic malignancies or complete myelodysplastic syndromes, but also when morphologic abnormalities occur in a single cell line. PMID- 1510035 TI - Proficiency testing of platelet counting in Ontario. AB - Proficiency testing results provide data for interlaboratory comparisons. The Laboratory Proficiency Testing Program of Ontario, Canada, has tested platelet counting for a decade and other hematology parameters for 15 years. Despite the fact that all testing programs are compromised by the type of testing material used, for platelet count testing, conclusions are possible. The data indicate that most laboratories in Ontario have greater difficulty performing reproducible platelet counting as compared with other components of hematologic cytometry. A major contributor to this shortfall is the method used by the laboratory. It was not a surprise that manual counting had a high coefficient of variation. Unexpectedly, the semiautomated methods used in the mid-1980s also displayed a high coefficient of variation. PMID- 1510036 TI - Imprecision of prothrombin time monitoring of oral anticoagulation. A survey of hospital laboratories. AB - Prothrombin time monitoring of oral anticoagulation is highly dependent on the tissue thromboplastin used. In the United States, patients have received a higher level of anticoagulation because of the use of a less sensitive thromboplastin. Many advocate the use of an International Normalized Ratio to rectify this problem. Laboratory supervisors from all acute care hospitals in Massachusetts were surveyed to determine the disparity in thromboplastin use and reporting practices for prothrombin time testing. Eighty-eight of 103 (86%) hospitals responded. Fifty-eight lots from six manufacturers of thromboplastin were in use. The International Sensitivity Index of these lots ranged from 1.89 to 2.74. Ninety-nine percent of hospitals reported prothrombin times in raw seconds. Only 5% reported an International Normalized Ratio. Sixteen different coagulation instruments were in use. Close to 70% of laboratory supervisors had little or no understanding of the significance of an International Sensitivity Index or an International Normalized Ratio. The management of oral anticoagulation appears far less precise than had been believed. Prothrombin times in the same individual from different laboratories may have poor correlation. Based on the level of understanding of laboratory supervisors, extensive education will be necessary to change practices and improve accuracy and comparability of prothrombin time testing. PMID- 1510037 TI - Clinically significant heparin carryover on the ACL 300R. AB - Investigation of a patient with an unexpected prolonged activated partial thromboplastin time showed on repeat testing that the patient had normal coagulation times, but had been preceded on the automated coagulation analyzer run (ACL 300R--Instrumentation Laboratory, Lexington, MA) by a heparin contaminated apheresis line sample taken from a different patient. Heparin carryover was suspected, and subsequent experiments showed that ex vivo heparinization of normal plasmas will produce similar effects in following normal plasma samples in a test series. This effect increases with the baseline activated partial thromboplastin time and the heparin concentration. It is recommended that coagulation analyzers that are susceptible to carryover be cleaned after testing of plasmas likely to have heparin concentration of more than 5 x 10(3) U/L. Furthermore, when using analyzers of this type, investigation of an unexplained activated partial thromboplastin time must include a review of the preceding samples tested, particularly when duplicate testing has been discontinued. PMID- 1510038 TI - Evaluation of serum immunoglobulins by protein electrophoresis and rate nephelometry before and after therapeutic plasma exchange. AB - One hundred fourteen pre- and postplasma exchange (PE) serum protein electrophoretograms and serum IgG, IgA, and IgM levels obtained during a 4-month period from 23 patients were evaluated. The interval between PE sessions varied from once daily to approximately once monthly. Typically, post-PE patterns had decreased alpha-1, decreased alpha-2, decreased beta, and decreased gamma fractions. The average percentage decreases of the immunoglobulins subsequent to PE were as follows: IgG, 52%; IgA, 55%; and IgM, 51%. There was a high linear correlation between the pre- and post-PE concentrations of IgG and IgA, whereas correlation of pre- and post-PE IgM concentrations was much lower. All IgG, IgA, and IgM levels (100%) returned to their respective reference intervals before subsequent PE when procedures were scheduled at least 2 weeks apart. When procedures occurred 1 week apart or less, only 1 IgG level (1%) returned to its reference interval, whereas 68 IgA (73%) and 74 IgM levels (80%) returned to their respective reference intervals. During this study, a faint monoclonal band was discovered in each of two patients. One had a normal baseline serum protein electrophoretogram before initiation of PE therapy, and the gammopathy was of uncertain significance. In the other patient, a vertebral plasmacytoma was discovered. It is concluded that PE reduces IgG, IgA, and IgM by approximately the same percentages; however, reference interval levels of IgA and IgM are restored more rapidly than IgG levels. Because monoclonal proteins may be present before or may appear during PE therapy, patients should be monitored by baseline and subsequent periodic serum protein electrophoresis. PMID- 1510039 TI - The anion gap. A reappraisal. PMID- 1510040 TI - Inaccurate results of urine dipstick tests. PMID- 1510041 TI - Monocyte count in Coulter STKS and MAXM. PMID- 1510042 TI - Cold agglutinin disease after chickenpox. PMID- 1510043 TI - Dental and orthopedic effects of high-pull headgear in treatment of Class II, division 1 malocclusion. AB - In the present study a prospective cephalometric investigation was undertaken to examine the skeletal and dental effects of the high-pull extraoral appliance, when the resultant force was directed through the level of trifurcation of the maxillary molars. Twelve adolescent patients with Class II, Division 1 malocclusions were selected for the study. Each patient wore the headgear for a 6 month period, an average of 12 hours a day. A group of untreated adolescent patients with Class II, Division 1 malocclusions who were in a similar age range, as well as skeletal and dental characteristics were chosen as controls. Lateral cephalometric films were taken before and after the 6-month treatment period, and before and after the observation period in the control group of patients. Our data indicate that by directing the force of the headgear approximately through the center of resistance of the maxillary molars, it is possible to accomplish simultaneously a substantial distal movement of the molars (2.6 +/- 0.6 mm), as well as significant intrusion (0.54 +/- 0.54 mm). In addition, our results demonstrate that the applied force of 500 gm was sufficient to initiate maxillary orthopedic changes in the treated patients. These changes include relative restriction of horizontal and vertical maxillary growth, as well as distal movement (mean: 0.8 mm) of the maxillary anterior border in the treatment group relative to an untreated control group. Such orthopedic changes have been previously described only in association with much higher force levels. PMID- 1510044 TI - Keep your eye on the star. Interview by Norman Wahl. PMID- 1510045 TI - Shear peel bond strengths of esthetic orthodontic brackets. AB - Anecdotal reports of bracket fracture and tooth damage associated with the use of certain esthetic orthodontic brackets have been reported in the literature. With the advent of new esthetic orthodontic brackets, the need has arisen to test the claims of the manufacturers. The objectives of this study were to determine: (1) shear peel bond strengths (SPBS) of various debonded orthodontic brackets, (2) SPBS of these rebonded esthetic brackets with and without use of silane, and (3) fracture sites of all groups examined. Seventy-five noncarious human premolar teeth were randomly divided into five groups (A through E). The teeth were cleaned, stored in 70% ethyl alcohol, and mounted for testing in the Instron machine. The following brackets were bonded to the teeth with Ortho-Concise bonding resin: (A) metal brackets, (B) Silkon brackets, (C) Transcend 2000 brackets, (D) debonded Transcend 2000 brackets, and (E) debonded silanized Transcend 2000 brackets. After wet storage at 37 degrees C for 7 days, the SPBS of brackets were recorded, and fracture sites observed. There were statistically significant differences between the SPBS of metal brackets when compared with the Transcend 2000 and the Silkon brackets. These groups exhibited clinically acceptable SPBS. Debonded silanized Transcend 2000 brackets showed clinically unacceptable SPBS. Fracture sites of metal and Transcend 2000 brackets were resin bracket, whereas Silkon brackets fracture sites were predominantly resin-enamel. PMID- 1510046 TI - The role of the condylar cartilage in mandibular growth. A study in thanatophoric dysplasia. AB - A new approach to evaluate the role of the condyle in mandibular growth could be its study in chondrodysplasias. The growth of the condylar cartilage and the mandible has not previously been reported in thanatophoric dysplasia (TD), a lethal osteochondrodysplasia. We have studied the light microscopic, histomorphometric, and radiologic findings in four infants affected by TD and in four control infants. The diagnosis was made on the basis of clinical, radiographic, and pathologic criteria. All the measured radiographic parameters of the patients' mandibles showed a normal longitudinal growth in TD, despite the severe disturbance of the condylar cartilages. The lesions in the chondroblastic cells and the extracellular matrix were similar to those observed in growth plate cartilages in TD. Marked membranous ossification spread from the cartilage canals of the condyles. The articular and prechondroblastic layers were histologically normal. Histomorphometry demonstrated that condylar cartilages were twice as thick as normal in TD, mainly because of the thickening by the chondroblastic layer. Present results support the hypothesis that condylar cartilage is a secondary growth site instead of being a primary growth center. PMID- 1510048 TI - Comments on diagnosis of skeletal form. PMID- 1510047 TI - Mandibular remodeling measured on cephalograms: 2. A comparison of information from implant and anatomic best-fit superimpositions. AB - This study quantifies the differences in the perceived pattern of mandibular remodeling when two different methods are used to superimpose roentgenographic images of the mandible. Lateral cephalograms for a group of subjects with metallic implants of the Bjork type were superimposed twice; first on the metallic implants and then independently on mandibular anatomic structures according to a common "best fit" rule. In this article, we compare the between superimposition differences in the perceived displacements of condyle, gonion, menton, pogonion, and Point B. Mean differences between the two superimpositional techniques were smaller than had been anticipated. For the 7-year time interval between 8.5 and 15.5 years, the largest mean differences between methods were 2.70 mm in the horizontal direction at condyle, 1.90 mm in the vertical direction at condyle, and 1.52 mm in the vertical direction at gonion. None of the other between-superimposition differences had a mean value in excess of 1 mm. The individual case variability between the two methods was, however, quite considerable, a finding that we believe has bearing on the confidence that can be placed in individual case analyses in clinical orthodontics. A preliminary attempt has been made to represent and discuss the magnitude of this problem. PMID- 1510049 TI - Evaluation of an anamnestic questionnaire as an instrument for investigating potential relationships between orthodontic therapy and temporomandibular disorders. AB - A group of 100 patients who received orthodontic treatment, between the ages of 16 to 31 years, were asked to complete the TMJ Scale (an anamnestic temporomandibular disorder [TMD] questionnaire) and undertake a simple clinical TMD examination, the Helkimo clinical dysfunction index. The purpose of this study was to compare the TMJ Scale and the Helkimo clinical dysfunction index to validate the use of the TMJ Scale as a potential method with which to examine whether there is any relationship between TMD and orthodontic therapy. Comparisons between TMJ Scale scores from the orthodontically treated group were made with previously reported TMJ Scale data. In addition, comparisons were made between various treatment and malocclusion groups identified within the orthodontically treated sample. On the basis of the TMJ Scale global scale scores for the orthodontically treated group and two normative nontemporomandibular disorder groups described by Levitt, Lundeen, and McKinney, no differences were observed. Similarly, TMJ Scale comparisons between various treatment and malocclusion subgroups showed no statistically significant differences. The results of this study support the use of the TMJ Scale as a valid instrument with which to determine whether there is any relationship between orthodontic therapy and TMD. PMID- 1510050 TI - Arch length considerations due to the curve of Spee: a mathematical model. AB - Arch length analysis should consider discrepancies not only within the sagittal plane but also within the vertical and transverse planes. The vertical deviation of the occlusal plane from a flat plane is known as the curve of Spee. The purpose of this study was to produce a mathematical model of the mandibular arch form in three planes of space and to determine the effect that the curve of Spee has on arch circumference. Two mandibular arch forms, the catenary and the Bonwill-Hawley, were examined. The curve of Spee was modeled as a cylinder perpendicular to the midsagittal plane centered on the arch anteroposteriorly. A mathematical distance formula was used to calculate arch circumferences from the central fossa of the first molars for 10 arches with curves of Spee ranging from 0 to 10 mm. This procedure was repeated for arch circumferences extending from the central fossa of the second molars. Plots for the difference in arch circumferences verses depth of the curve of Spee showed that the relationship between these two variables is not linear and is less than one to one. This model showed that clinical practice of allowing 1 mm of arch circumference for leveling each millimeter of curve of Spee overestimates the amount of arch circumference needed to flatten the curve of Spee. PMID- 1510051 TI - The effects of infraocclusion: Part 1. Tilting of the adjacent teeth and local space loss. AB - The normal arrangement of the transseptal fibers in the dentition is one of a completely horizontal system that links the mesial and the distal aspects of each tooth within the dental arch, from the most distal tooth of one side to the most distal tooth of the other, across the midline. This continuous fiber band is parallel to the occlusal plane, being attached to each tooth coronal to the level of the interradicular alveolar bone crest and apical to the cementoenamel junction. Alteration of the occlusal plane will be mirrored by a similar change in the plane of the transseptal fiber system. From the clinical observation of young people with infraoccluded deciduous teeth, over many years, the regular and concomittant occurrence of certain other, well-defined phenomena appears to be the rule. It was thought that these phenomena could be explained in terms of the inclusion of a vertical component (infraocclusion) into this horizontal system. Two of these phenomena are discussed here. The first and most obvious of these relates to the exaggerated tipping that affects the adjacent tooth mesially and distally. The second parameter measures the amount of actual horizontal (mesiodistal) space change that occurs locally, within the dental arch, between the two teeth adjacent to the infraoccluded tooth, measured at both the occlusal level and at the level of their root apices. With a high degree of statistical validity, it was found that infraocclusion is related to severe tilting of the two adjacent teeth toward the affected tooth, with minimal space loss in the dental arch at the occlusal level, but a wide separation of root apices. PMID- 1510052 TI - Relations between verbal behavior of the orthodontist and communicative cooperation of the patient in regular orthodontic visits. AB - A study of interrelationships between orthodontist and patient communication characteristics on the basis of audiotape recordings is reported. The subjects were 66 patients from an orthodontic outpatient clinic who were treated by seven orthodontists. Strong relationships (partial correlations) were found between clinicians encouraging behavior (listener signals and symmetrical answering) and patient communicative cooperation (speech volume, detailed answering, questions, initiatives); whereas orthodontists guiding behavior showed lower correlations, only the clinicians' direct questions were significantly related to patient participation. For communication content, relations to patient activity depended on how strongly orthodontists discussed social or therapy topics. Discussion characteristics of both parties were not related to the patient's age, sex, and duration of therapy. However, patient communication differed with the personality of the dentist. Results are discussed with reference to literature, orthodontic consulting practice, and future research. PMID- 1510053 TI - Correction of a superiorly displaced impacted canine due to a large dentigerous cyst. AB - One of the more difficult situations dealt with by orthodontists is the treatment of impacted maxillary canines. This case report describes an impacted canine positioned near the floor of the orbit that was brought into a normal position. Diagnostic records revealed impacted and displaced teeth resulting from a large radiolucent lesion. The patient was referred to an oral surgeon. The lesion was diagnosed as a dentigerous cyst and marsupialized over 12 months. After decompression of the cyst, the impacted teeth were exposed and orthodontically brought into their proper position. PMID- 1510054 TI - Angle classification revisited 2: a modified Angle classification. AB - Edward Angle, in his classification of malocclusions, appears to have made Class I a range of abnormality, not a point of ideal occlusion. Current goals of orthodontic treatment, however, strive for the designation "Class I occlusion" to be synonymous with the point of ideal intermeshing and not a broad range. If contemporary orthodontists are to continue to use Class I as a goal, then it is appropriate that Dr. Angle's century-old classification, be modified to be more precise. PMID- 1510055 TI - Reconditioning and reuse of orthodontic devices. PMID- 1510056 TI - Positional asphyxiation in adults. A series of 30 cases from the Dade and Broward County Florida Medical Examiner Offices from 1982 to 1990. AB - Over a 9-year period, 30 cases of positional (or postural) asphyxia were identified in the Dade and Broward County (Florida) Medical Examiner Offices. The victims had an average age of 50.6 years with no significant sex or racial differences as compared with the general medical examiner population. Chronic alcoholism or acute alcohol intoxication was a significant risk factor in 75% of cases and these had an average postmortem ethanol concentration of 0.24 g%. Signs of mechanical asphyxiation (petechiae and/or combined lung weights greater than 900 g) were present in 93% of cases. Victims were commonly (43%) found in a restrictive position producing hyperflexion of the head and neck. Two deaths involved restraint vests ("poseys") in elderly, demented, wheel-chair-confined victims. Scene photographs of the undisturbed decedent are extremely helpful in confirming a suspicion of postional asphyxia. PMID- 1510057 TI - An unusual accidental death from reverse suspension. AB - Deaths involving prolonged suspension head downwards have received little or no attention in the English-language literature, doubtless because they are extremely rare. An example, involving alcoholic intoxication as the sole complicating factor, is reported. The mechanism of death is also considered since this is plainly a subject of some interest and likely to provoke further thought and discussion. PMID- 1510058 TI - Death by power car window. An unrecognized hazard. AB - The unusual accidental asphyxial death of a 26-month-old girl involving a car power window is reported. The circumstances and investigation results are discussed, as well as how such tragedies may be avoided. PMID- 1510059 TI - Atypical autoerotic deaths. AB - So-called "typical" autoerotic fatalities are the result of asphyxia due to mechanical compression of the neck, chest, or abdomen, whereas "atypical" autoeroticism involves sexual self-stimulation by other means. We present five atypical autoerotic fatalities that involved the use of dichlorodifluoromethane, nitrous oxide, isobutyl nitrite, cocaine, or compounds containing 1-1-1 trichloroethane. Mechanisms of death are discussed in each case and the pertinent literature is reviewed. PMID- 1510060 TI - Does advancing age modify the presentation of disease? AB - A group of patients who had died of either cardiac tamponade due to ruptured myocardial infarct, perforated peptic ulcer, or diverticulitis with perforation were studied to determine the effect that age has on the presentation of these three potentially fatal diseases. With advanced age, a decrease in the number of patients who had symptoms typical for the disease that was ultimately the cause of death was found. We also noted a number of patients who did not experience any symptoms, and some patients who experienced symptoms that were not typical of their disease. In many instances, the disparity between disease severity and symptoms had resulted in the disease not being diagnosed either because the patient did not seek medical advice or because the doctor was unable to make the appropriate diagnosis from the patient's symptoms. PMID- 1510061 TI - The development of forensic medicine in the United Kingdom from the 18th century. AB - Forensic medicine in the United Kingdom includes both forensic pathology and clinical forensic medicine on the living. It began at the end of the 18th century, long after its development in Germany, Italy, France, and other countries in Europe. Initial beginnings were in Scotland, where a program began at the University of Edinburgh with the establishment of a chair in Forensic Medicine by Prof. Andrew Duncan Sr. The development in England began in London's Kings College Medical School with a chair held by Prof. William A. Guy. Later chairs in Forensic Medicine were established in Glasgow, Aberdeen, and in London, where Forensic Medicine was taught at St. Mary's Hospital Medical School, Guy's Hospital Medical School, London Hospital Medical School, Charing Cross Hospital Medical School, St. Thomas Hospital Medical School, and St. George's Hospital Medical School. In other cities in England, Wales, and Northern Ireland, departments were founded in Leeds, Manchester, Cardiff, and Belfast. Many textbooks were prepared during this time by professors from these medical schools and by others working in nonacademic areas. The development of coroner activities and those of the police surgeons is also part of the study of forensic medicine. PMID- 1510062 TI - The Office of Forensic Medicine, Victoria, Australia. PMID- 1510063 TI - Sudden death due to self-treatment of peripheral edema with rubberband tourniquet. AB - A 70-year-old white male alcoholic with a history of congestive heart failure associated with peripheral edema was found dead in a pool of blood with a circumferential laceration of his right leg. A rubberband was found around the leg deep within the wound. The decedent reportedly refused medical treatment for his cardiovascular condition and treated himself by applying rubberbands and bandages around his legs to stop the spread of edema and infection. PMID- 1510064 TI - Esophageal-atrial fistula resulting in systemic "meat and vegetable" emboli. AB - An 85-year-old demented woman died in the state hospital and her death was investigated by our office, based on allegations of neglect. At autopsy, a feeding catheter was found passed through an esophageal-atrial fistula into the left atrium. Fragments of striated muscle and plant wall (cellulose) embolized to the systemic organs including heart, kidney, and brain. Her dilated esophagus suggests a premortem esophageal motility disorder that contributed to the formation of the fistula. This is the first reported case of an esophageal-atrial fistula in the medical literature. PMID- 1510065 TI - Body packing with a twist. Death of a salesman. AB - Reported cases of death due to oral ingestion of lidocaine are rare. We report the case of a known cocaine dealer who died after swallowing a small packet of white powder, thought to be cocaine, during a relatively routine arrest. The authors describe how the deceased differed from the usual "body packer" and alert the forensic community to be wary of what may first appear to be another "garden variety" cocaine death. PMID- 1510066 TI - Forensic anthropology in the 1990s. AB - Forensic anthropology has undergone considerable change over the past 10 years. Today it is utilized by most law enforcement, coroner, and medical examiner systems. The techniques for determination of age at death, sex, race, and stature from skeletal remains have been modified and greatly expanded. The role of the forensic anthropologist within a medicolegal context is much broader than in previous years. In addition to establishing individual identity, forensic anthropologists are now consulted for trauma analysis, facial reconstruction, photographic superimposition, determination of time interval since death, and crime-scene recovery. Not all physical anthropologists are forensic anthropologists. Qualified individuals are certified, through rigorous examination, by the American Board of Forensic Anthropology. A list of board certified forensic anthropologists may be obtained through the American Academy of Forensic Sciences. PMID- 1510067 TI - The descriptive epidemiology of unnatural deaths in Oregon's state institutions: a 25-year (1963-1987) study. II. Analysis of the incidence rate and its many variations. AB - We have analyzed suicide data of the Forensic Psychiatric Program of the Oregon State Hospital in terms of the various ways of expressing occurrence rates that are found in the literature. All of these rates are ultimately based upon either (a) the average daily population, computed from occupancy rates of institutional beds, or (b) a measure of the total number of individuals at risk (that is, all who were in the study population during the time frame of the study). We discuss reasons for the use of these different rates. We have also calculated the risk of suicide for each of two factors: (a) the primary psychiatric diagnosis and (b) the type of legal commitment under which these patients were admitted to the Forensic Psychiatric Program. We discovered that virtually the entire risk of suicide in this program was borne by patients whose primary diagnosis was that of chronic schizophrenia and who were committed there because of diminished criminal responsibility for a crime of which they were found guilty in a court of law. PMID- 1510068 TI - The descriptive epidemiology of unnatural deaths in Oregon's state institutions: a 25-year (1963-1987) study. III. A 25-year overview of unnatural deaths in the mental and correctional facilities. AB - I document 25 consecutive years (1963-1987) of unnatural deaths within the State of Oregon's mental and correctional institutions in Marion County. This study includes 93 unnatural deaths in the Oregon State Hospital, 18 in the Forensic Psychiatric Program, 52 in the Fairview Training Center, and 45 in the Corrections Department facilities. These institutional unnatural deaths are compared with the 2,618 unnatural deaths that occurred during this same period in Marion County (exclusive of these state facilities). Death rates are shown in five 5-year blocks of time to illustrate death trends. Accidents and suicides were the predominant types of unnatural death in the Oregon State Hospital; suicides predominated in the Forensic Psychiatric Program and the corrections facilities; and accidents predominated in the Fairview Training Center. Extremely high total unnatural death rates were found in the Oregon State Hospital (approximately 520/100,000 or 8.46 times that found in Marion County) and the Forensic Psychiatric Program (approximately 561/100,000 or 9.13 times that found in Marion County). The overall accident death rate for the Fairview Training Center was approximately 119/100,000 or 2.84 times that found in Marion County. The overall total unnatural death rate for the corrections facilities was approximately 75/100,000 or 1.23 times that found in Marion County. I compare these data with those of other investigators in the United States, Canada, and western Europe. The total unnatural death rate appears to represent a valid criterion of violent death within a community. PMID- 1510069 TI - Diffuse axonal injury by simple fall. AB - Diffuse axonal injury (DAI) is the second most common lethal head trauma after subdural hematoma and probably the most frequent cause of traumatic coma in the absence of an expanding intracranial mass lesion. Though it occurs most often in traffic accidents, it may occasionally result from falls from a height. Previously, it has not been associated with a simple fall or a fall of a distance not more than the victim's own height. We report herein a case of DAI from a simple fall. PMID- 1510070 TI - Mattresses, beds, and bedding in deaths of infants. PMID- 1510071 TI - Waterbeds and sudden infant death syndrome. PMID- 1510072 TI - Demonstration of a fatal hemolytic transfusion reaction using immunoperoxidase techniques. PMID- 1510073 TI - A forensic application of DNA typing. PMID- 1510074 TI - Gunshot residue and range of fire. PMID- 1510075 TI - An unusual entrance wound associated with rimfire rifles. PMID- 1510076 TI - Exhumed presidents' society. PMID- 1510077 TI - Positional asphyxia during law enforcement transport. AB - Three cases of positional asphyxia are described that occurred while victims were in a prone position in rear compartments of police patrol cars. These deaths are attributed to positional asphyxia. Autopsy findings and specific scene and circumstantial correlations of the investigation are discussed with emphasis placed on the limitations of interpretation of the anatomic changes at autopsy. PMID- 1510078 TI - The perils of investigating and certifying deaths in police custody. AB - Procedures leading to the proper investigation and certification of deaths occurring in police custody are discussed. The importance of training and experience, of interchange of information between investigator and forensic pathologist, and of common sense in the pursuit of fairness toward this end is emphasized. PMID- 1510079 TI - Prevalence of coronary heart disease in subjects with normal and impaired glucose tolerance and non-insulin-dependent diabetes mellitus in a biethnic Colorado population. The San Luis Valley Diabetes Study. AB - The prevalence of coronary heart disease was studied in 1984-1988 in 1,092 individuals with normal glucose tolerance, 173 individuals with impaired glucose tolerance, and 429 individuals with non-insulin-dependent diabetes mellitus, who were age 25-74 years and were from a biethnic community in the San Luis Valley, Colorado. Glucose tolerance was classified using the World Health Organization criteria, and coronary heart disease prevalence was assessed using the Rose Questionnaire and a resting electrocardiogram. Compared with normal glucose tolerance, coronary heart disease was significantly more prevalent in diabetic non-Hispanic white women (odds ratio (OR) for all end points combined = 3.2, 95% confidence interval (Cl) 1.8-5.5) and men (OR = 1.9, 95% Cl 1.1-3.3) and in diabetic Hispanic women (OR = 1.7, 95% Cl 1.1-2.5), but not men (OR = 1.0, 95% Cl 0.6-1.7). Among diabetic men, the prevalence of possible myocardial infarction was lower in Hispanics than in non-Hispanic whites (OR = 0.4, 95% Cl 0.2-0.7). Similar patterns of coronary heart disease were observed in individuals with impaired glucose tolerance. The paradoxically low prevalence of coronary heart disease in Hispanics with non-insulin-dependent diabetes mellitus, especially men, may be due to unknown protective factors, increased case fatality, or competing mortality in this group. PMID- 1510080 TI - Educational status and blood pressure: the Second National Health and Nutrition Examination Survey, 1976-1980, and the Hispanic Health and Nutrition Examination Survey, 1982-1984. AB - An inverse association between socioeconomic status, as measured by years of education, and blood pressure has been reported in a number of studies. However, two secular trends may have changed the nature of this relation: a higher mean level of education in the population and intervention for high blood pressure in the community. Given that education is the most commonly used indicator of social class and measurement is a critical issue in epidemiologic research, a study was initiated to examine the validity of education for predicting blood pressure among 11,554 examined persons aged 25-74 years from the Second National Health and Nutrition Examination Survey (1976-1980) or the Hispanic Health and Nutrition Examination Survey (1982-1984). In univariate analysis, a consistent, inverse association between education and blood pressure was found for whites and blacks, but not for Mexican Americans. After adjustment for age and body mass, the effect persisted only for systolic blood pressure in whites. The association of education and blood pressure was positive in Mexican-American females. Education was inversely related to hypertensive status in whites and in black females. These findings suggest that information on education may be of little value for identifying populations at risk of high blood pressure, particularly if age and body mass are known. However, information on education may be of considerable value in the design and implementation of appropriate interventions. PMID- 1510081 TI - Increased mortality from brain tumors: a combined outcome of diagnostic technology and change of attitude toward the elderly. AB - United States national data were used to assess factors responsible for the increase of brain tumor mortality. Between 1968 and 1988, death rates increased 50% among those aged 65-74 years, 200% among those aged 75-84 years, and 800% in the oldest old. Rate of increase and maximum death rate have changed over time. Death rate among the population aged 65-74 years peaked in the mid-1980s, while among those aged 85 years and older it is projected to continue increasing throughout the 1990s. The patterns of rate increases were almost identical in the two sexes, as well as among whites and nonwhites. There was a strong correlation over time of death rates with head diagnostic procedures (r = 0.96) and with the pace of computerized axial tomography installation (r = 0.91). The authors conclude that the reported increase in brain tumor mortality is not genuine, but represents a combination of three factors: availability of more sophisticated, noninvasive diagnostic technology; change in the attitude toward care of the elderly; and introduction of support programs such as Medicare that facilitate diagnostic procedures in the elderly. PMID- 1510082 TI - Influence of the mother's prenatal drug consumption on risk of neuroblastoma in the child. AB - A case-control study was conducted 1) to determine whether maternal prenatal drug consumption increases the risk of neuroblastoma in the child and, if so, 2) to see if the size of the risk depends on whether the case is inherited or sporadic. Mothers of children with newly diagnosed neuroblastoma (n = 101) were compared with mothers of children newly diagnosed with other forms of childhood cancer (n = 690). Cases and controls were selected from the population of childhood cancer patients at St. Jude Children's Research Hospital, Memphis, Tennessee, between 1979 and 1986. The patients' mothers were interviewed to ascertain their prenatal medication, alcohol, and tobacco consumption patterns. Unconditional logistic regression models were used to adjust for maternal age at birth, patient age at diagnosis, race, social class, exposure to x-ray, miscarriage, and other confounding variables. Adjusted odds ratios were estimated for the total sample and for subgroups that had a higher probability of containing inherited cases. Drugs associated with neuroblastoma case status include diuretics for hypertension (odds ratio (OR) = 4.1, 95 percent confidence interval (CI) 1.0 16.9), tranquilizers (OR = 2.1, 95 percent CI 1.1-4.3), nonprescription pain relievers (OR = 1.9, 95 percent CI 1.1-3.1), and cigarettes (OR = 1.9, 95 percent CI 1.1-3.2). The odds ratios for maternal prenatal drug consumption for the group with inherited cases and the total sample were approximately the same. This equality is inconsistent with predictors based on Knudson's two-stage model of carcinogenesis. PMID- 1510084 TI - Differences in cause-specific infant mortality among Chinese, Japanese, and white Americans. AB - Although black-white differences in infant mortality have received much attention, information is limited about mortality differentials among Asian Americans. This study investigated racial differences in infant mortality in a sample of 21,288 Chinese, 11,882 Japanese, and 65,818 white resident singleton livebirths obtained from the National Center for Health Statistics 1983 and 1984 linked birth/infant death files. The crude infant mortality rates were 8.03, 6.56, and 8.46 per 1,000 livebirths for Chinese, Japanese, and white births, respectively. Cause-specific mortality varied considerably among the three racial groups. While the Japanese had lower rates of infant deaths and deaths from perinatal conditions for firstborn infants, they had higher rates of sudden infant death syndrome, as did Chinese females. The results of a logistic regression analysis indicate that the racial differences in total and cause specific mortality persist when adjustment is made for demographic factors, use of prenatal care, infant sex, and birth weight. The effect of these latter variables on infant mortality varied by causes of death. The relations between infant mortality and variables such as marital status, maternal education, and birth interval appear indirect, operating partially through birth weight. While birth weight was the single strongest determinant of infant mortality, its relative importance varied by cause of death. The study findings suggest that policy decisions surrounding racial differences in infant mortality should not only be considered in light of specific races, but also with regard to cause specific mortality. Moreover, additional research is needed to understand the cultural, biological, and behavioral factors that give rise to the racial differences. PMID- 1510083 TI - Menstrual function after tubal sterilization. AB - More than 10 million women in the United States have undergone tubal sterilization. There has been concern that this procedure may increase the risk of later menstrual dysfunction. The Collaborative Review of Sterilization (CREST) is a large, multicenter, prospective study of tubal sterilization in the United States. This report describes CREST participants who were interviewed immediately before sterilization and again in annual poststerilization interviews for up to 5 years between 1978 and 1988. The authors analyzed reported changes in six menstrual cycle characteristics for 5,070 women undergoing interval sterilizations. Longitudinal, multivariate regression was used to adjust for baseline menstrual function and other potential confounders. Five years after sterilization, 35% of the CREST participants reported high levels of menstrual pain, 49% reported heavy or very heavy menstrual flow, and 10% reported spotting between periods. In contrast to the fifth year, the first year of follow-up was similar to presterilization menstrual function; in the first year, 27% of participants reported high menstrual pain, 41% reported heavy menstrual flow, and 7% reported spotting. These findings may be affected by aging of the cohort and other study limitations, but they suggest that if tubal sterilization leads to changes in menstrual function, such changes may take some time to develop. PMID- 1510085 TI - Parental cigarette smoking and the risk of spontaneous abortion. AB - Although cigarette smoking is often considered a risk factor for spontaneous abortion, the epidemiologic literature is actually inconsistent. Therefore, the authors examined maternal and paternal smoking and maternal passive smoke exposure using data from a large case-control study of spontaneous abortion (626 cases and 1,300 controls) conducted in Santa Clara County, California, in 1986 and 1987. No excess risk of spontaneous abortion was seen in the 1% of women who smoked an average of more than 20 cigarettes per day in the first trimester. Moderate smokers (11-20 cigarettes per day) had a slightly elevated crude odds ratio of 1.3 (95% confidence interval 0.9-1.9), which was close to unity after adjustment for covariates. Paternal smoking showed a slight crude elevation for moderate and heavy smoking, but no association after adjustment. In contrast, maternal exposure to environmental tobacco smoke for 1 hour or more per day was associated with spontaneous abortion, even after adjustment (odds ratio = 1.5, 95% confidence interval 1.2-1.9). For both maternal direct and environmental exposure, the association appeared to be stronger in second-trimester abortions. Several studies have found stronger associations of smoking with late versus early abortions, perhaps reflecting smoking-associated placental insufficiency and fetal hypoxia. PMID- 1510086 TI - A trichinosis outbreak among Southeast Asian refugees. AB - The number of cases of trichinosis reported to Centers for Disease Control has declined steadily, with an average of only 44 cases per year from 1984 through 1988. This decline was almost entirely due to a reduction in cases acquired from ingestion of fresh commercial pork. However, from July 21 through September 3, 1990, 90 (72%) of 125 Southeast Asian refugees from six states and Canada developed trichinosis after attending or eating pork sausage taken from a wedding held in Des Moines, Iowa, on July 14, 1990. Eating uncooked sausage prepared at home from commercially obtained pork was associated with the development of this illness (odds ratio = 34.0, p less than 0.001). Analysis by amount of pork consumed was significant (Mann-Whitney U rank sum test, p less than 0.001). This outbreak of trichinosis in Iowa is the fourth reported within the last 15 years among the 900,000 Southeast Asian refugees resident in the United States and one of the largest reported outbreaks in US history. The continued presence of Trichinella spiralis in commercial pork emphasizes the need for further education and control measures for persons whose dietary habits place them at risk for developing trichinosis. PMID- 1510087 TI - Re: "Occupational exposure to electromagnetic fields and breast cancer in men". PMID- 1510088 TI - Re: "Cocaine use during pregnancy: perinatal outcomes". PMID- 1510089 TI - Re: "The 'fourth disease' of childhood: reevaluation of a nonexistent disease". PMID- 1510090 TI - Re: "Does nondifferential misclassification of exposure always bias a true effect toward the null value?". PMID- 1510091 TI - Turning the boss around. PMID- 1510092 TI - Using muscle in the fight against falls. PMID- 1510093 TI - Have you mastered 'stresscalation'? PMID- 1510094 TI - Distinct disadvantage. PMID- 1510095 TI - Are we stealing nurses? PMID- 1510096 TI - The public-health perspective. PMID- 1510097 TI - How do you treat--and control--C. difficile infection? PMID- 1510098 TI - The move to patient-focused care. PMID- 1510099 TI - Peripheral vascular disease. Is it arterial or venous? PMID- 1510100 TI - Rape: how to begin the healing. PMID- 1510102 TI - When your patient is allergic. PMID- 1510101 TI - Overcoming LVD in cardiac rehab. PMID- 1510103 TI - The emergency nurse's world: always changing, always challenging. PMID- 1510104 TI - Is everything everyone's job? PMID- 1510105 TI - Job sharing: two who made it work. PMID- 1510106 TI - Essential nursing references. Interagency Council on Library Resources for Nursing. PMID- 1510107 TI - AIDS-infected nurse to get $5.4 million. PMID- 1510108 TI - Sexual dimorphism in the human bony pelvis, with a consideration of the Neandertal pelvis from Kebara Cave, Israel. AB - Sexual dimorphism of the human pelvis is inferentially related to obstetrics. However, researchers disagree in the identification and obstetric significance of pelvic dimorphisms. This study addresses three issues. First, common patterns in dimorphism are identified by analysis of pelvimetrics from six independent samples (Whites and Blacks of known sex and four Amerindian samples of unknown sex). Second, an hypothesis is tested that the index of pelvic dimorphism (female mean x 100/male mean) is inversely related to pelvic variability. Third, the pelvic dimensions of the Neandertal male from Kebara cave, Israel are compared with those of the males in this study. The results show that the pelvic inlet is the plane of least dimorphism in humans. The reason that reports often differ in the identification of dimorphisms for this pelvic plane is that both the length of the pubis and the shape of the inlet are related to nutrition. The dimensions of the pelvis that are most dimorphic (that is, female larger than male) are the measures of posterior space, angulation of sacrum, biischial breadth, and subpubic angle. Interestingly, these dimensions are also the most variable. The hypothesis that variability and dimorphism are inversely related fails to be supported. The factors that influence pelvic variability are discussed. The Kebara 2 pelvis has a spacious inlet and a confined outlet relative to modern males, though the circumferences of both planes in the Neandertal are within the range of variation of modern males. The inference is that outlet circumference in Neandertal females is also small in size, but within the range of variation of modern females. Arguments that Neandertal newborns were larger in size than those of modern humans necessarily imply that birth was more difficult in Neandertals. PMID- 1510109 TI - Brief communication: interproximal tooth wear: a new observation. AB - Microscopic observations were made of wear on the proximal surfaces of tooth crowns of Australian Aboriginals and whites. Typical wear facets displayed well defined borders within which vertical or near vertical furrows, ranging from about 0.1 to 0.5 mm in width, were noted. Furrows on the interproximal surface of one tooth seemed to "interdigitate" with those on the proximal surface of the adjacent tooth. These observations are not consistent with the commonly-held view that interproximal tooth wear results from a buccolingual movement of adjacent teeth that maintain contact through mesial migration. Vertical or near vertical movement of teeth, possibly including a tipping action, must be an important factor, although the precise nature of the movement requires further investigation. PMID- 1510110 TI - Cranial thickening and anemia: reply to Dr. Webb. PMID- 1510111 TI - Cranial thickening: a reply to Dr. Stuart-Macadam. PMID- 1510112 TI - Unusual pathological condition in the lower extremities of a skeleton from ancient Israel. AB - We report here an unusual pathology in a 1,500-year-old skeleton recovered from Bet Guvrin, Israel. The pathological changes in the lower extremities and the diagnostic difficulties are presented. We attribute this condition to Madura foot, found primarily in tropical and subtropical regions, although other diagnoses are possible and are noted. We discuss its appearance in the region in light of the historical context. PMID- 1510113 TI - Origin of the Koreans: a population genetic study. AB - A population genetic study was undertaken to investigate the origin of Koreans. Thirteen polymorphic and 7 monomorphic blood genetic markers (serum proteins and red cell enzymes) were studied in a group of 437 Koreans. Genetic distance analyses by both cluster and principal components models were performed between Koreans and eight other populations (Koreans in China, Japanese, Han Chinese, Mongolians, Zhuangs, Malays, Javanese, and Soviet Asians) on the basis of 47 alleles controlled by 15 polymorphic loci. A more detailed analysis using 65 alleles at 19 polymorphic loci was performed on six populations. Both analyses demonstrated genetic evidence of the origin of Koreans from the central Asian Mongolians. Further, the Koreans are more closely related to the Japanese and quite distant from the Chinese. The above evidence of the origin of Koreans fits well with the ethnohistoric account of the origin of Koreans and the Korean language. The minority Koreans in China also maintained their genetic identity. PMID- 1510114 TI - Allometry and prediction in hominoids: a solution to the problem of intervening variables. AB - To avoid misinterpretation of allometric exponents determined from interspecific allometric comparisons, specific conditions must be met with respect to the common reference variable. Body weight is considered to be the best general indication of overall size and is hence widely acknowledged to be the most suitable reference variable. However, because of the paucity of recorded body weights for museum specimens, various comparative studies have used other size indicators as intervening variables, although the allometric relationships to body size/weight were often unknown and possibly differed between species. Because of differences in the scaling properties of alternative intervening variables across the species investigated, conflicting conclusions may be drawn if different variables are chosen as substitutes for overall size. This is illustrated with two examples. In this study, series of skeletons with associated body weights of Gorilla, Pan, Pongo, and Homo were investigated. Both ontogenetic and static adult allometric relationships between several widely used reference variables and body weight were determined. Neither these variables nor additional estimators investigated in this study displayed allometric exponents and coefficients similar enough across species to justify direct interspecific comparison. To generate an alternative size estimator for both ontogenetic and static interspecific investigations, equations for combined sexes were derived to predict body weight from various long bone dimensions for individual hominoid species. From a total of 25 predictors, 12 prediction equations per species (six for nonadults and six for adults) were selected according to their relative suitability for reliable prediction of body weight. It is shown that the derived reference variable "predicted body weight" avoids problems of intervening variables, is valid for any interspecific ontogenetic and static allometric comparison, and displays less fluctuation in comparison to actual body weight. PMID- 1510115 TI - Three-dimensional finite element stress analysis of the dentate human mandible. AB - The biomechanical events which accompany functional loading of the human mandible are not fully understood. The techniques normally used to record them are highly invasive. Computer modelling offers a promising alternative approach in this regard, with the additional ability to predict regional stresses and strains in inaccessible locations. In this study, we built two three-dimensional finite element (FE) models of a human mandible reconstructed from tomographs of a dry dentate jaw. The first model was used for a complete mechanical characterization of physical events. It also provided comparative data for the second model, which had an increased vertical corpus depth. In both cases, boundary conditions included rigid restraints at the first right molar and endosteal cortical surfaces of the articular eminences of temporal bones. Groups of parallel multiple vectors simulated individual masticatory muscle loads. The models were solved for displacements, stresses, strains, and forces. The simulated muscle loads in the first model deformed the mandible helically upward and toward its right (working) side. The highest principal stresses occurred at the bite point, anterior aspects of the coronoid processes, symphyseal region, and right and left sides of the mandibular corpus. In general, the observed principal stresses and strains were highest on the periosteal cortical surface and alveolar bone. At the symphyseal region, maximum principal stresses and strains were highest on the lower lingual mandibular aspect, whereas minimum principal stresses and strains were highest on its upper labial side. Subcondylar principal strains and condylar forces were higher on the left (balancing or nonbiting) side than on the right mandibular side, with condylar forces more concentrated on the anteromedial aspect of the working-side condyle and on the central and lateral aspects of the left. When compared with in vivo strain data from macaques during comparable biting events, the predictive strain values from the first model were qualitatively similar. In the second model, the reduced tensile stress on the working-side, and decreased shear stress bilaterally, confirmed that lower stresses occurred on the lower mandibular border with increased jaw depth. Our results suggested that although the mandible behaved in a beam-like manner, its corpus acted more like a combination of open and closed cross sections due to the presence of tooth sockets, at least for the task modelled.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1510116 TI - Gummivory and gut morphology in two sympatric callitrichids (Callithrix emiliae and Saguinus fuscicollis weddelli) from western Brazilian Amazonia. AB - A comparative analysis of the gastrointestinal tracts of wild-caught marmosets, Callithrix emiliae, and tamarins, Saguinus fuscicollis weddelli, was undertaken in order to evaluate the degree of specialisation for digestion of plant exudates. Compared to S.f. weddelli, C. emiliae exhibits a reduced small intestine and a relatively large, compartmentalised caecum in which gum is probably fermented. The apparent specialisation of the digestive tract in C. emiliae correlates with that of its dentition, which is adapted for gouging the bark of gum-producing plants. A similar degree of specialisation of the caecum is predicted for other marmosets (Callithrix spp. and Cebuella pygmaea). PMID- 1510117 TI - Lipid peroxidation in isolated rat nephron segments. AB - Elevated levels of lipid peroxides (LPO) in tissues have been considered an index of increased reactive oxygen metabolites, which are important pathological mediators also found in the kidney. By adopting the quantification of malondialdehyde-thiobarbituric acid adduct as a standard, using a fluorometer, a microassay was developed that enabled us to measure LPO in tissue having less than 1 microgram protein. By this method, basal levels of LPO along the rat nephron showed that proximal tubules bear more LPO per millimeter of tubule than distally located segments (approximately 0.2 pmol/mm tubule for proximal tubules and 0.02 for thick ascending limbs) and that S3 was the highest LPO per tissue protein (2.2 +/- 0.1 pmol/microgram protein, n = 8). In addition, the levels of LPO were stimulated by 10 microM phorbol 12-myristate 13-acetate (PMA) in both glomeruli and S3 (P less than 0.001) and in S2 (P less than 0.05). Furthermore, sphingosine (100 microM), a protein kinase C (PKC) inhibitor, totally blocked the LPO increment by PMA without any effect on the basal LPO in glomeruli, suggesting the involvement of PKC in LPO formation. Taken together, the results indicate the applicability of LPO assay to the nephron for evaluation of site-specific nephrotoxic insult and its mechanisms in renal pathophysiology. PMID- 1510118 TI - Role of endothelium-derived relaxing factor in renal autoregulation in conscious dogs. AB - In six chronically instrumented, conscious dogs the hypothesis was tested that the release of endothelium-derived relaxing factor (EDRF) is important for autoregulation of renal blood flow (RBF) and glomerular filtration rate (GFR). RBF was measured by a Transonic flowmeter. Renal perfusion pressure was servo controlled by an aortic cuff. EDRF synthesis was inhibited by NG-nitro-L-arginine methyl ester (L-NAME, 50 mg/kg iv). L-NAME increased mean systemic blood pressure (30 mmHg) and decreased heart rate (-40 beats/min), but it left autoregulation of RBF and GFR intact. However, basal RBF decreased markedly (2.24 +/- 0.32 ml.min 1.g-1 with L-NAME vs. 3.91 +/- 0.64 ml.min-1.g-1 for control, P less than 0.01), whereas basal GFR was not significantly influenced (0.37 +/- 0.05 ml.min-1.g-1 with L-NAME vs. 0.42 +/- 0.06 ml.min-1.g-1 for control). Hence filtration fraction increased with L-NAME [27.6 +/- 1.7% vs. 19.3 +/- 1.3% (P less than 0.01)]. The lower limit of autoregulation remained unchanged for RBF (64 +/- 5 mmHg with L-NAME vs. 63 +/- 3 mmHg for control) and increased slightly for GFR (74 +/- 2 mmHg with L-NAME vs. 67 +/- 1 mmHg for control, P less than 0.01). In conclusion, basal EDRF activity tonically influences renal resistance vessels; however, EDRF release is not primarily involved in the process of renal autoregulation. The maintenance of GFR suggests that this effect is localized in preglomerular as well as in postglomerular arterioles. PMID- 1510119 TI - Role of intracellular calcium in hydrogen peroxide-induced renal tubular cell injury. AB - Both reactive oxygen metabolites and calcium have been implicated in ischemic and toxic renal tubular cell injury. However, the role of calcium in oxidant injury to renal tubular cells has not been previously examined. In the present study we examined the role of intracellular free Ca2+ ([Ca2+]i) in H2O2-mediated injury to LLC-PK1 cells, a renal tubular epithelial cell line. H2O2 induced a significant rise in [Ca2+]i within 1 min after exposure of cells to 5 mM H2O2, with a sustained rise in [Ca2+]i during the course of experiments, reaching a value of 1.3 microM at 60 min (n = 10). The rise in [Ca2+]i preceded sublethal cell injury as measured by [3H]adenine release or irreversible cell injury as determined by trypan blue exclusion. Buffering [Ca2+]i with quin-2 (50 microM) and 1,2-bis(2 aminophenoxy)ethane-N,N,N',N'-tetraacetic acid (BAPTA, 50 microM) was highly protective against the H2O2-induced cell injury. For example, at 120 min after exposure of cells to 5 mM H2O2, irreversible cell injury was reduced from 45 +/- 8 to 9 +/- 1% (n = 3) by quin-2. The acetoxymethyl ester of quin-2 (quin-2/AM) and BAPTA/AM did not interfere with the trypan blue exclusion assay or scavenge H2O2. Preventing mobilization of Ca2+ from intracellular storage sites using 8 (N,N-dimethylamino)octyl 3,4,5-trimethoxybenzoate hydrochloride (TMB-8, 10(-4) M) significantly reduced the rise in [Ca2+]i and thus prevented H2O2-mediated cytotoxicity to LLC-PK1 cells.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1510120 TI - Comparative effects of arginine vasopressin and oxytocin in cell culture systems. AB - Arginine vasopressin (AVP) and oxytocin (OXT) induced contraction in cultured vascular smooth muscle cells (VSMC) and glomerular mesangial cells (GMC). The contractile response of AVP and OXT was paralleled by Ca2+ mobilization as assessed by 45Ca2+ efflux in a dose-dependent manner. The effects of AVP were blocked by pretreating VSMC and GMC with a V1 antagonist. OXT-stimulated effects, however, were not affected by preexposure of VSMC and GMC to an OXT antagonist but were inhibited by the V1 antagonist. Competition studies demonstrated displacement of [3H]AVP from its receptors by unlabeled AVP, the V1 antagonist, and high doses of OXT. The OXT antagonist was the least effective in displacing [3H]AVP. Thus occupancy of the V1 receptor by OXT may initiate signal transduction and contraction in VSMC and GMC in a manner qualitatively similar to that of the AVP agonist. Cultured myometrium cells (MMC) also contracted in response to AVP and OXT. Moreover, 45Ca2+ efflux increased in response to both hormones in a dose-dependent manner. AVP-stimulated contraction and 45Ca2+ efflux were blocked in MMC by pretreatment with V1 antagonist. OXT-induced effects were inhibited by the OXT antagonist but not by the V1 antagonist. Binding experiments showed that [3H]AVP was displaced equally by unlabeled AVP and V1 antagonist. Very high concentrations of OXT antagonist also demonstrated displacement.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1510121 TI - Paradoxical exacerbation of leukocyte-mediated glomerulonephritis with cyclooxygenase inhibition. AB - Nephrotoxic nephritis (NTN) is characterized by glomerular inflammation, an increase in glomerular eicosanoid synthesis, and renal dysfunction. Data further suggest that eicosanoids may play a critical role in the inflammatory response. In the current study, we examined the effects of in vivo manipulation of arachidonate metabolism on the cellular component of the inflammatory response in NTN. We found that inhibition of cyclooxygenase with indomethacin in mild NTN caused a two- to fourfold increase in the leukocyte influx into glomeruli with a change histologically from a focal to a more diffuse lesion. Both the accompanying proteinuria and the increase in ex vivo glomerular eicosanoid production were also augmented by the administration of indomethacin. The effect of indomethacin was reversible and not limited to the acute phase of NTN. The administration of aspirin, like indomethacin, augmented the glomerular inflammation of NTN. Neither OKY-046 (a thromboxane synthase inhibitor) nor MK 886 (a 5-lipoxygenase inhibitor) altered the glomerular inflammation of NTN. Administration of exogenous prostaglandin E (in the form of misoprostol) did diminish the proteinuria accompanying NTN; however, glomerular inflammation was not significantly affected. Incubation of glomeruli with [14C]arachidonate demonstrated the presence of noncyclooxygenase pathways of arachidonate metabolism (11-, 12-, and 15-lipoxygenases) with increased activity in NTN. These data demonstrate that cyclooxygenase inhibition may paradoxically worsen glomerular inflammation and suggest a potential role for noncyclooxygenase/non-5 lipoxygenase pathways of arachidonate metabolism. PMID- 1510122 TI - Endothelium-derived relaxing factor regulates renin release in vivo. AB - Endothelium-derived relaxing factor (EDRF), through its inhibitory second messenger guanosine 3',5'-cyclic monophosphate (cGMP), inhibits renin release in vitro. To determine whether EDRF affects renin in vivo, we tested whether EDRF synthesis inhibition could stimulate renin secretion in intact rats. Because EDRF synthesis inhibition increases blood pressure and consequently withdraws sympathetic activity (both renin inhibitory signals), we also studied the effect of L-N omega-nitroarginine methyl ester (L-NAME) when renal perfusion pressure was controlled and during beta-adrenergic blockade. Mean blood pressure (BP), heart rate (HR), and plasma renin activity (PRA) were measured in anesthetized rats before and after EDRF synthesis inhibition by a 10 mg/kg body wt bolus of L NAME. L-NAME decreased PRA by 67% [from 11.0 +/- 2.7 to 3.7 +/- 0.8 ng angiotensin I (ANG I).ml-1.h-1, n = 12; P less than 0.001], increased BP by 20 +/ 2 mmHg (P less than 0.001), and decreased HR from 332 +/- 8 to 312 +/- 9 beats/min (P less than 0.005). We repeated our experiment in rats instrumented with an intra-aortic balloon catheter to control renal perfusion pressure and pretreated with propranolol to eliminate the beta-adrenergic effect. Under these conditions, L-NAME now increased PRA by 55% (from 6.9 +/- 1.9 to 10.8 +/- 2.6 ng ANG I.ml-1.h-1, n = 12; P less than 0.02), whereas renal perfusion pressure was unchanged (91 +/- 4 vs. 90 +/- 4 mmHg). HR increased slightly from 308 +/- 5 to 315 +/- 3 beats/min (P less than 0.005).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1510123 TI - Basolateral membrane potassium channels in rabbit cortical thick ascending limb. AB - The nature of K exit across the basolateral membrane of rabbit cortical thick ascending limb (CTAL) was investigated using the patch clamp technique. The basolateral membrane was exposed by mild collagenase treatment (0.1 U/ml), and a K-selective inwardly rectifying channel was identified. In cell-attached patches (140 mM K pipette) the inward conductance was 35.0 +/- 1.3 pS (n = 9) compared with an outward conductance of 7.0 +/- 0.9 pS (n = 5), and the current reversed at a pipette potential of -63.5 +/- 3.1 mV (n = 9). The channel is strongly voltage dependent, showing an e-fold increase in open probability per 18-mV depolarization. Barium blocked the channel, reducing both mean open probability and single-channel current amplitude; however, the channel was not Ca sensitive. On excision the channel exhibited rundown, which could not be prevented by 0.1 mM ATP or ATP plus 20 U/ml catalytic subunit of protein kinase A. A few excised patch recordings were possible, which confirmed the presence of a highly K selective channel with a K-to-Na permeability ratio of 100. In conclusion, 1) it is possible to obtain patch clamp recordings from the rabbit CTAL basolateral membrane using a very mild collagenase treatment, and 2) the exit of K across the basolateral membrane is mediated at least in part by the presence of voltage sensitive K channels. PMID- 1510124 TI - Effect of ANG II receptor antagonist on albuminuria and renal function in passive Heymann nephritis. AB - Angiotensin-converting enzyme inhibitors reduce albuminuria in nephrotic subjects, but the hormonal mechanism of this effect is not known. To determine whether specific inhibition of angiotensin (ANG) II activity would decrease albuminuria as occurs after converting enzyme inhibition, rats with passive Heymann nephritis received enalapril or the ANG II receptor antagonist losartan (6 mg.kg-1.day-1) for 4 days. Enalapril reduced both albuminuria (from 583 +/- 53 to 286 +/- 55 mg/day, P less than 0.001) and the fractional clearance of albumin (FCAlb) each day after starting treatment but did not affect glomerular filtration rate (GFR). Losartan reduced albuminuria significantly only after 4 days of treatment, but this value was not different from controls. GFR significantly increased with losartan (from 1.24 +/- 0.09 to 1.73 +/- 0.21 ml/min, P less than 0.05) so that FCAlb was reduced (from 0.0134 +/- 0.0027 to 0.0080 +/- 0.0018, P less than 0.05). Blood pressure decreased only in the enalapril group. Although plasma renin activity increased and the pressor response to ANG I was inhibited by both enalapril and losartan, suggesting effective peripheral blockade of ANG II activity, a third group of nephrotic rats was treated with losartan (18 mg.kg-1.day-1) to ensure that adequate ANG II blockade was achieved. Blood pressure decreased 10 mmHg, GFR increased from 1.35 +/- 0.14 to 1.79 +/- 0.12 ml/min (P less than 0.01), but albuminuria and FCAlb did not change. Urinary total kallikrein excretion was increased only in nephrotic rats treated with enalapril. Although both enalapril and losartan reduce ANG II activity, only the converting enzyme inhibitor reduces albuminuria.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1510125 TI - Both peripheral chylomicron catabolism and hepatic uptake of remnants are defective in nephrosis. AB - We showed previously that proteinuria caused delayed chylomicron (CM) clearance in the rat and postulated the existence of a primary defect in CM hydrolysis. It was possible that reduced CM clearance resulted from increased lipogenesis causing saturation of catabolic sites and not from a primary defect in CM catabolism. To clarify this point we measured kinetically the absolute rate of triglyceride (TG) uptake from CM in rats with Heymann nephritis (HN) and normal Sprague-Dawley rats (SD) and determined TG uptake in individual tissues using [3H]TG- and [14C]cholesterol-labeled CM. Hepatic [14C]cholesterol uptake was reduced in HN (69.3 +/- 6 vs. 7.2 +/- 2% of dose, P less than 0.001). TG uptake was reduced in HN measured kinetically (1.01 +/- 0.09 vs. 0.213 +/- 0.028 mg TG.min-1.100 g body wt-1, P less than 0.001) and reduced in all tissues (heart, skeletal muscle, fat, and liver). CM are catabolized on the vascular endothelium to atherogenic, cholesterol-rich remnant (CM remnant) particles, which are then rapidly taken up by the liver. We measured hepatic CM remnant uptake in SD and in HN using [14C]cholesterol-labeled CM remnant. CM remnant uptake was significantly reduced in HN (58 +/- 1.2 vs. 20 +/- 0.86% uptake, P less than 0.01). CM remnants were increased significantly in plasma of HN. Thus the nephrotic syndrome causes a primary defect in the uptake of TG from CM that is expressed in all tissues and a separate defect in hepatic CM remnant uptake. Although CM remnant generation is impaired because of defective CM hydrolysis, the defect in hepatic CM remnant uptake is so severe that these particles accumulate in blood, posing a potential risk for atherogenesis. PMID- 1510126 TI - Relationship between HCO3- transport and oxidative metabolism in rabbit proximal tubule. AB - HCO3-/CO2 can affect proximal tubule energy metabolism directly by serving as a substrate for metabolic reactions and indirectly through ATP utilization by HCO3( )-coupled Na+ reabsorption and proton secretion. In this study, metabolic and transport roles of HCO3-/CO2 were examined by measuring the effects of HCO3-/CO2 removal and transport inhibitors on oxygen consumption (QO2) in suspensions of rabbit proximal tubules. Removal of medium HCO3-/CO2 inhibited ouabain-sensitive, ouabain-insensitive, and uncoupled QO2. Consistent with metabolic inhibition, the absence of HCO3-/CO2 also reduced tubule ATP content and stimulated lactate production. Analysis of the dependence of mitochondrial state 3 respiration on HCO3-/CO2 in digitonin-permeabilized tubules traced the metabolic inhibition to limitations in tricarboxylic acid cycle intermediate supply. Energy requirements for HCO3- transport were examined by measuring QO2 in response to acetazolamide, 4,4'-diisothiocyanostilbene-2,2'-disulfonic acid (DIDS) and 4-acetamido-4' isothiocyanostilbene-2,2'-disulfonic acid (SITS), and the H(+) adenosinetriphosphatase (H(+)-ATPase) inhibitor bafilomycin A. Acetazolamide had no effect on QO2, whereas DIDS-SITS and bafilomycin A reduced ouabain-insensitive QO2, consistent with inhibition of active proton secretion. DIDS-SITS did not affect ouabain-sensitive respiration, suggesting that HCO3(-)-dependent Na+ reabsorption may not be mediated through the Na(+)-K(+)-ATPase in this preparation. PMID- 1510127 TI - Venous myogenic tone: studies in human and canine vessels. AB - Active and passive mechanical properties of human saphenous and canine femoral and saphenous vein segments were measured in vitro to assess the degree of pressure-dependent venous myogenic tone (% change in diameter, physiological saline solution vs. Ca(2+)-free solution) in these vessels. Stepwise elevation of intraluminal pressure from 2 to 20 mmHg caused an active myogenic response, which was calcium dependent. Side branches of human saphenous veins (OD at 20 mmHg: 1.92 +/- 0.15 mm control; 2.41 +/- 0.18 mm relaxed) displayed a larger degree of myogenic tone (approximately 25%) compared with dog saphenous (OD: 2.84 +/- 0.16 mm control; 2.89 +/- 0.16 mm relaxed) and femoral (OD: 3.56 +/- 0.32 control; 3.66 +/- 0.31 mm relaxed) veins (2-3%). This alteration in myogenic tone results in over 120% change in lumen capacity for the human saphenous vein, whereas for the dog saphenous and femoral veins, the change in lumen capacity is less than 10%. The vessels showed a constriction to norepinephrine as well as a reversible dilation to Ca(2+)-free perfusion. These results support the hypothesis that an active myogenic response may play an important role in the regulation of vascular capacity in the human saphenous vein, which is subject to substantial pressure variations due to changing orthostatic loads. PMID- 1510128 TI - Free radicals mediate endothelial cell dysfunction caused by elevated glucose. AB - Impaired endothelium-dependent relaxation occurs in diabetic rabbit aorta and normal aorta exposed to elevated concentrations of glucose and is prevented by cyclooxygenase inhibitors. The role of free radicals in the endothelial cell impairment was examined with free radical scavengers and in aortas from rabbits fed with probucol (1% wt/wt, a lipid-soluble antioxidant). Rings of aorta suspended for measurement of isometric tension were incubated for 6 h in control (5.5 mM) or elevated (44 mM) glucose. Impairment of endothelium-dependent relaxation to acetylcholine caused by exposure to elevated glucose was prevented by superoxide dismutase, catalase, deferoxamine, or allopurinol and did not occur in aortas from probucol-fed rabbits. Similarly, impairment of acetylcholine relaxations in aortas from alloxan-induced diabetic rabbits was restored to normal by superoxide dismutase. Oxygen-derived free radicals generated by xanthine oxidase also caused impaired acetylcholine relaxations. Exposure of aortic segments to elevated glucose or to xanthine oxidase caused a significant increase in release of immunoreactive prostanoids. These data indicate that the endothelial cell dysfunction caused by elevated glucose is mediated by free radicals that are likely generated through the increased cyclooxygenase catalysis occurring in the endothelium. Treatment with antioxidants protects against impaired endothelium-dependent relaxations caused by elevated glucose. PMID- 1510129 TI - Initiation and development of calcium waves in rat myocytes. AB - To understand the characteristics of asynchrony in spontaneously occurring increases in cytoplasmic calcium concentrations ([Ca2+]i) in the cardiac myocyte, we observed newly developed changes in regional [Ca2+]i after a physical injury to the sarcolemma. Myocytes were isolated from rat left ventricle and loaded with acetoxymethyl ester of fura-2. We analyzed dynamic changes in fluorescence images by video densitometry. After the injury was imposed, three types of responses were observed: 1) rapid contracture with steady increase in [Ca2+]i; 2) periodic development of a calcium wave; and 3) quiescence after the injury. In some myocytes with the second type of response, a sustained burst of calcium waves was observed. In myocytes in which multiple calcium waves are present simultaneously, a propagated wave can reset a cycle of wave generation at the wave focus. Waves disappear after their collision, which indicates the existence of a refractory period after the calcium transient. The wave originating from the focus with the fastest frequency dominates the whole cell. Thus dynamic changes in regional [Ca2+]i are asynchronous but are organized by the following principles: 1) a regional increase in [Ca2+]i can propagate; 2) a propagated calcium wave can reset a cycle of wave initiation at the focus; and 3) a regional calcium transient leaves a refractory period. PMID- 1510130 TI - Effects of allopurinol on reperfusion arrhythmias in isolated ventricles. AB - Electrophysiological effects of allopurinol on arrhythmias were studied in isolated segments of guinea pig right ventricular free walls paced from endocardium. A high-gain electrocardiogram as well as transmembrane electrical activity from endo- and epicardium were recorded. Tissues were exposed to simulated ischemia for 15 min and then were reperfused with normal Tyrode solution. Sustained or nonsustained ventricular tachycardia, bigeminy, and trigeminy with characteristics of transmural reentry occurred in early reperfusion in 75% of 20 control preparations. Arrhythmias were associated with prolongation of transmural conduction time and abbreviation of endocardial effective refractory period (ERP). Allopurinol strongly reduced the incidence of reperfusion arrhythmias (20-33%) between 10 and 100 microM, whereas either lower or higher concentrations (5 or 500 microM) were less effective (43 and 50%). Antiarrhythmic efficacy correlated with significant attenuation of reperfusion induced transmural conduction delay (P less than 0.05 or 0.01). Allopurinol did not affect endocardial conduction times nor did it significantly alter endocardial action potential duration or ERP. Our results indicate that allopurinol exerts antiarrhythmic efficacy during reperfusion by selectively attenuating defects related to anisotropic tissue properties. PMID- 1510131 TI - Platelet amplification of vasospasm. AB - Platelets may accentuate vasoconstriction in stenotic arteries capable of vasomotion. We examined the interaction of platelets, stenosis, and arterial vasoconstriction in normal and stenotic arteries with intact endothelium. Beagle carotid arteries (n = 38) were isolated, removed, and placed in an in vitro perfusion system. Platelet-rich plasma (PRP) or platelet-poor plasma (PPP) were perfused through the arteries under constant pressure (100 mmHg) and a fixed distal resistance. In intact arteries without a stenosis, angiotensin II (ANG II) decreased luminal diameter without altering flow during PRP perfusion. After creating an intraluminal stenosis, vasoconstriction produced by ANG II resulted in near total cessation of flow. During PRP perfusion, this effect was amplified, demonstrating suppression of flow at significantly (P less than 0.05) lower concentrations of ANG II (PRP, ED50 = 0.03 +/- 0.01 x 10(-8) M) compared with arteries perfused with PPP (PPP, ED50 = 2.7 +/- 0.8 x 10(-8) M). This accentuated vasoconstrictor response in the presence of platelets was not blocked by SKF 96148 (a thromboxane A2 antagonist) but was abolished by ketanserin (a 5-HT2 serotonergic blocker). This increased sensitivity to vasoconstriction was not due to significant platelet plugging inasmuch as no cyclic flow reductions were observed, aspirin (acetylsalicylic acid) did not prevent this accentuated vasoconstrictor response, and adventitial administration of nitroglycerin restored flow to baseline levels. These studies illustrate that 1) platelets amplify the effect of vasoconstrictors in stenotic arteries, 2) this amplification of vasoconstriction is primarily due to platelet release of serotonin, and 3) the amplification occurs in the absence of significant platelet plugging and endothelial damage. PMID- 1510133 TI - Calmodulin stimulation of smooth muscle plasmalemmal vesicle Ca2+ uptake: direct or indirect effect? AB - Current evidence suggests that Ca(2+)-calmodulin-dependent protein kinase(s) may be involved in the regulation of smooth muscle contractility. The plasmalemmal Ca2+ pump plays an important role in smooth muscle contractility, and this pump is stimulated by calmodulin. However, it is not known whether this is due to direct activation, or calmodulin-dependent protein phosphorylation, or both. We tested these hypotheses using a plasma membrane vesicle preparation from porcine antral smooth muscle. Inclusion of calmodulin in the Ca(2+)-uptake assay decreased the free Ca2+ concentration at which Ca2+ uptake is 50% of the maximal rate (1.5 +/- 0.21 to 0.84 +/- 0.06 microM) of the Ca2+ pump for Ca2+, without changing maximal rate of Ca2+ uptake (Vmax) (8.0 +/- 1.1 to 8.4 +/- 0.7 nmol.min 1.mg-1). In contrast, prephosphorylation in the absence of Ca(2+)-calmodulin increased Ca(2+)-uptake rates at both low (pCa 6.0) and high Ca2+ concentration (pCa 5.0), suggesting an increase in Vmax. Further phosphorylation in the presence of Ca(2+)-calmodulin was not associated with any further increases in the Ca(2+)-uptake rates at pCa 6.0. However, inclusion of calmodulin in the Ca(2+)-uptake assays stimulated the rates (pCa 6.0) of both unphosphorylated and prephosphorylated vesicles to a similar extent. These findings suggest that the stimulation of the smooth muscle plasmalemmal Ca2+ pump by calmodulin is predominantly due to a direct effect via a mechanism distinct from that by plasma membrane phosphorylation. PMID- 1510132 TI - Role of endothelium and hyperpolarization in CGRP-induced vasodilation of rabbit ophthalmic artery. AB - The electromechanical effects of calcitonin gene-related peptide (CGRP) on intact and endothelium-denuded rabbit ophthalmic arteries were studied. CGRP inhibited norepinephrine (NE)-induced contractions. In intact arteries after washout of CGRP the contractile sensitivity to NE was increased. Conversely, in endothelium denuded arteries, the relaxation induced by CGRP was prolonged, and after washout of CGRP the contractile sensitivity to NE was diminished. In intact arteries NE contractions were enhanced by NG-monomethyl-L-arginine (L-NMMA), an inhibitor of endothelium-derived relaxing factor (EDRF) synthesis, and in the presence of L NMMA, CGRP-induced relaxations resembled those seen in endothelium-denuded arteries. This result suggests that there is an increased EDRF synthesis in intact arteries during NE stimulation and that CGRP may inhibit either the synthesis or the activity of EDRF. High concentrations of CGRP hyperpolarized the smooth muscle membrane both in intact and endothelium-denuded arteries. Hyperpolarizations were blocked by glibenclamide, indicating that they are mediated by activation of ATP-sensitive K+ channels. However, glibenclamide had little effect on the CGRP-induced relaxation. These results suggest that in normal physiological conditions CGRP-induced relaxation of the rabbit ophthalmic artery is mediated mainly by mechanisms other than hyperpolarization. PMID- 1510134 TI - Effects of exercise training on vasomotor reactivity of porcine coronary arteries. AB - The purpose of this study was to determine whether exercise training induces changes in the contractile behavior of proximal coronary arteries. Female Yucatan miniature swine were either exercise trained (ET) on a motor-driven treadmill or allowed to remain sedentary (SED) for 16-22 wk. Responses to vasoactive compounds were evaluated in vitro using coronary arterial rings (approximately 2 mm diam) isolated from ET and SED pigs. Each ring was stretched to the apex of the length active tension relationship. Concentration-response relationships for isometric contractions evoked with KCl (5-100 mM), prostaglandin F2 alpha (PGF2 alpha; 10( 8)-3 x 10(-5) M), acetylcholine (ACh; 10(-9)-10(-4) M), and endothelin (10(-10) 10(-7) M) were similar in arteries from SED and ET pigs. In contrast, arteries from the ET group developed 50-60% less maximal tension in response to norepinephrine (NE; 10(-6)-10(-4) M) than did controls. Vasodilator responses of rings precontracted with either KCl or PGF2 alpha were evaluated with adenosine (ADO; 10(-9)-10(-4) M), isoproterenol (10(-9)-10(-4) M), forskolin (10(-9)-10(-4) M), and sodium nitroprusside (NP; 10(-10)-10(-4) M). Vasodilator responses were similar in SED and ET groups for all agents except ADO and NP; arteries from ET pigs were more sensitive to ADO and less sensitive to NP. The ET-induced alterations in vasomotor responses to NE and ADO appear to be due to changes in vascular smooth muscle because they were still present after removal of endothelium. We conclude that chronic exercise training in pigs induces selective alterations in NE and ADO receptor-second messenger coupling and/or postreceptor related events in epicardial coronary vascular smooth muscle. PMID- 1510135 TI - Almitrine mimics hypoxic vasoconstriction in isolated rat lungs. AB - The effect of almitrine bimesylate or the solvent malic acid on pulmonary vascular perfusion pressure was assessed in isolated rat lungs and on the contractile behavior of rat aorta and main pulmonary artery rings. Addition of almitrine to the lung perfusate during normoxia caused a dose-dependent, transient increase in pulmonary artery pressure with no change of the lung microvascular pressure. In systemic or pulmonary conduit arteries, the contractile tension was unaffected by almitrine. This indicates a precapillary locus of drug action. We also examined almitrine's effect on hypoxic pulmonary vasoconstriction (HPVC) in isolated lungs perfused with blood or with physiological salt solution (PSS). Low-dose almitrine potentiated hypoxic vasoconstriction in blood- but not in PSS-perfused lungs. However, a high dose of almitrine reduced hypoxic vasoconstriction dose dependently. When almitrine was added to the lung perfusate during hypoxia- or cyanide-induced (NaCN, 5 x 10(-5) M) pulmonary vasoconstriction, almitrine caused no further vasoconstriction. However, when the pulmonary perfusion pressure was elevated by KCl (20 mM) to the same magnitude as by alveolar hypoxia or cyanide, almitrine elicited a pressor response comparable to that observed during normoxia. Almitrine-induced pulmonary vasoconstriction resembled hypoxic vasoconstriction in that agents known to enhance hypoxic vasoconstriction (phorbol myristate acetate, vanadate, and 4 aminopyridine) enhanced, and known inhibitors of HPVC (the Ca2+ entry blocker nifedipine and hypothermia) inhibited, the almitrine-induced vasoconstriction. These findings lead us to speculate that almitrine also affects the oxygen sensing limb of the hypoxic pressor response, not simply the effector (contractile apparatus of the vascular muscle cell). PMID- 1510136 TI - Effect of superoxide dismutase and catalase on regional dysfunction after exercise-induced ischemia. AB - This study was designed to test the hypothesis that the oxygen free radical scavengers superoxide dismutase (SOD) and catalase may reduce myocardial "stunning" after exercise-induced ischemia. To test this hypothesis, 8 mongrel dogs performed treadmill exercise for 10 min in the presence of a flow-limiting coronary artery stenosis. Regional left ventricular function was measured with ultrasonic microcrystals implanted to measure regional wall thickening. Regional myocardial perfusion was measured with radioactive microspheres. The combination of SOD (5 mg/kg iv) and catalase (5 mg/kg iv) did not affect heart rate, blood pressure, coronary artery flow, or regional myocardial blood flow at rest, during exercise, or in the postexercise period. SOD and catalase had no effect on regional wall thickening at rest before exercise. During exercise in the absence of a coronary artery stenosis, thickening was slightly lower during SOD and catalase infusion (27 +/- 11.0 vs. 30.8 +/- 11.5%, SOD vs. control P = 0.05). During exercise in the presence of a coronary artery stenosis, there was no difference in thickening. Infusion of SOD and catalase affected neither the transient rebound function occurring early after exercise nor the prolonged period of stunning. These results indicate that the myocardial stunning that follows exercise-induced ischemia is unlikely to be mediated by oxygen free radicals. PMID- 1510137 TI - Glibenclamide decreases basal coronary blood flow in anesthetized dogs. AB - The effects of ATP-sensitive K+ channel blockade on coronary blood flow were studied in 13 anesthetized open-chest dogs. A specific ATP-sensitive K+ channel blocker, glibenclamide, was infused into the left circumflex coronary artery (LCx). Coronary blood flow of LCx and systolic segment shortening at the LCx area were measured. Intracoronary infusion of glibenclamide (0.5, 5, and 50 micrograms.kg-1.min-1) decreased coronary blood flow dose dependently. Glibenclamide at the dose of 50 micrograms.kg-1.min-1 decreased LCx coronary blood flow by 55 +/- 4% (P less than 0.01), which was accompanied by a decrease in percentage segment shortening at the LCx area (P less than 0.01) and ST elevation. When coronary blood flow was maintained at the baseline level by simultaneous infusion of sodium nitroprusside (1-3 micrograms/min ic) or pinacidil (0.3-0.6 mg/min ic), glibenclamide did not alter percentage segment shortening or produced ST elevation. The latter results suggest that glibenclamide decreased coronary blood flow, which secondarily induced myocardial ischemia and dysfunction. Our results suggest that ATP-sensitive K+ channels of coronary arteries are involved in maintaining the level of resting coronary blood flow under physiological conditions in anesthetized dogs. PMID- 1510138 TI - Hemodynamic and proteolytic effects of intravenous injection of purified human plasma kallikrein. AB - To investigate the precise hemodynamic effects of purified human plasma kallikrein, small doses (0.3 U/kg) of this proteolytic enzyme were infused over 10 s in five pigs. Hemodynamic performance was evaluated by means of a Swan-Ganz catheter, and parameters of the plasma kallikrein-kinin, coagulation, and fibrinolytic systems were determined by means of chromogenic peptide substrate assays. The infusions of plasma kallikrein were followed by rapid decreases in mean arterial pressure (to 43 +/- 2% of baseline values) and increases in cardiac output (to 145 +/- 6% of baseline values), accounting for marked decreases in systemic vascular resistance, to 28 +/- 1% of initial values. Heart rate, mean pulmonary arterial, central venous, and pulmonary capillary wedge pressures did not change after the injection. Pulmonary vascular resistance decreased to 69 +/- 3% of baseline values. The hemodynamic changes gradually normalized during the following 10 min. Functional levels of prekallikrein, kallikrein, kallikrein inhibition, prothrombin, antithrombin III, plasmin, and antiplasmin were not affected by the injection or the resulting hemodynamic changes; the hematocrit and the number of circulating leukocytes or platelets were also unaffected. PMID- 1510139 TI - Influence of long-chain acylcarnitines on voltage-dependent calcium current in adult ventricular myocytes. AB - Long-chain acylcarnitines (LCAC) increase 3.5-fold within 2 min in ischemic myocardium in vivo, and previous studies have suggested, through indirect evidence, that LCAC can stimulate the voltage-dependent L-type Ca2+ current [ICa(L)] in both cardiac and smooth muscle cells. In the present study, whole cell voltage-clamp procedures were performed in isolated adult guinea pig ventricular myocytes to assess the direct effect of LCAC on ICa(L). The intracellular solution contained (in mM) 80 CsCl, 40 K-aspartic acid, and 5 ethylene glycol-bis(beta-aminoethyl ether)-N,N,N',N'-tetraacetic acid (EGTA). Maximal current density of ICa(L) at 0 mV was 10.1 +/- 0.5 pA/pF (n = 22) at extracellular Ca2+ concentration ([Ca2+]o) = 2.7 mM. LCAC induced a concentration (1-25 microM, n = 23)- and time-dependent, reversible decrease in ICa(L). When delivered extracellularly for 10 min, LCAC (5 microM) inhibited the maximal current of ICa(L) by 48.1 +/- 1.3% (n = 9, P less than 0.01) and shifted the half maximal voltage of steady-state activation and inactivation from -13.1 +/- 0.5 to -6.8 +/- 0.4 mV (n = 4; P less than 0.05) and from -21.8 +/- 0.2 to -16.5 +/- 0.6 mV (n = 4; P less than 0.01), respectively. Intracellular delivery of LCAC (5 microM) also suppressed ICa(L) to a similar degree (47.5 +/- 1.5%, n = 4; P less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1510140 TI - Metabolism of angiotensin I by different tissues in the intact animal. AB - To quantify regional conversion of angiotensin (ANG) I to ANG II and its degradation to peptides other than ANG II, monoiodinated 125I-labeled ANG I was given to anesthetized pigs by constant infusion into the left cardiac ventricle. At steady state, blood samples were taken from the aorta and various regional veins. Distribution volume of ANG I appeared to be 24% of body weight. After angiotensin-converting enzyme (ACE) inhibitor treatment, fractional ANG I metabolism (fraction of arterially delivered ANG I that was metabolized during a single passage of blood) was 10% in the lungs (conversion 4%), compared with 56% in the combined systemic vascular beds (conversion 1%). Fractional ANG I metabolism during ACE inhibition was 93% in the kidney; 50-70% in myocardium, skeletal muscle, head, and skin; 21% in the left cardiac cavity; and 14% in the right cardiac cavity. Without ACE inhibition, fractional ANG I metabolism was 29% in the lungs (conversion 25%); 49% in the combined systemic vascular beds (conversion 10%); 38% in the left cardiac cavity (conversion 11%); and 14% in the right cardiac cavity (conversion 0%). It may thus be concluded that 1) extrapulmonary vascular beds make an important contribution to the conversion of circulating ANG I and 2) there is rapid extrapulmonary ANG I degradation that does not depend on ANG I-II conversion. PMID- 1510141 TI - Production of angiotensins I and II at tissue sites in intact pigs. AB - To estimate the contribution of angiotensin (ANG) I and II production at tissue sites to the circulating levels, ANG I and II and their radiolabeled counterparts were measured in arterial and venous plasma across various vascular beds during constant infusion of 125I-ANG I into the left cardiac ventricle of anesthetized pigs. In the combined systemic vascular beds, ANG I production was closely correlated with plasma renin activity (PRA) and ANG II production was greater than in the lungs. In the lungs virtually no ANG I but 31% of ANG II in venous plasma was derived from de novo production, which could be fully accounted for by conversion of circulating ANG I. In myocardium, head, skin, skeletal muscle, and kidney, respectively, 40, 58, 55, 67, and 94% of venous ANG I, and 32, 49, 40, 59, and 85% of venous ANG II were derived from de novo production. In these extrapulmonary beds part of de novo produced ANG I and II appeared not to be generated, respectively, by PRA and by conversion of circulating ANG I. These results indicate that production of ANG I at tissue sites contributes to its circulating level and that some circulating ANG II may not be derived from circulating ANG I. PMID- 1510142 TI - Synthesis and transport of lipoprotein lipase in perfused guinea pig hearts. AB - Total lipoprotein lipase (LPL) activity did not differ significantly between hearts from fed or fasted guinea pigs. Incorporation of [35S]methionine into immunoprecipitable LPL was also the same. The rates at which perfused hearts from fed or fasted guinea pigs released LPL activity into the medium were, however, different (2 vs. 4 mU.g-1.min-1). These rates remained constant over 60 min of perfusion. Addition of heparin to the medium resulted in a peak of LPL activity during the first 2 min, followed by a shoulder of relatively high activity, which gradually declined to a constant rate from 30 min. The peak and shoulders were less with hearts from fed animals than with hearts from fasted animals, but the constant rates were similar. Cycloheximide added at the start of the perfusion had no effect on the peak or on the early part of the shoulder, but the LPL activity released from 30 min continuously decreased so that at 60 min it was less than half of that in controls. Studies in which the enzyme was pulse labeled by perfusion 15 min with medium containing [35S]methionine and then chased up to 75 min with unlabeled medium showed no differences in how LPL is transported and metabolized in hearts from fed vs. fasted guinea pigs. Thus the data suggest that factors outside the heart influence the disposition of heart LPL in vivo. PMID- 1510143 TI - Dynamic response of coronary regulation to heart rate and perfusion changes in dogs. AB - The rate of change of coronary adjustment in the anesthetized dog to a step change in heart rate (HR) and in perfusion was analyzed. The left main coronary artery was perfused either at constant pressure (CP) or at constant flow (CF). Coronary arterial pressure and flow were continuously measured and averaged per beat, after which their ratio, being an index of coronary resistance in steady state, was calculated. The rate of change of pressure-to-flow ratio was quantified by t50, the time required to establish half of the completed response. The t50 values for the dilating responses at CP were 5.5 +/- 0.4 (SE) s for an increase in HR and 5.5 +/- 0.1 s for a decrease in perfusion. At CF these values were 9.3 +/- 0.9 and 9.7 +/- 1.6 s, respectively. The t50 values for the constricting responses with CP were 6.6 +/- 0.5 s for a decrease in HR and 6.2 +/ 0.2 s for an increase in perfusion. At CF these values were 12.2 +/- 1.5 and 10.8 +/- 2.2 s. The responses in the dog are faster than in the goat. Furthermore, the directional sensitivity in responses with perfusion changes, observed earlier in goats, is normally absent in dogs. PMID- 1510144 TI - Control of ventricular fibrillation after coronary artery occlusion via intracerebroventricular injections. AB - The central nervous system (CNS) may play a larger role than previously thought in the development of ventricular fibrillation after coronary artery occlusion. The probability of ventricular fibrillation after complete, permanent occlusion of the left anterior descending coronary artery was 52% in conscious control pigs. After the administration into the lateral cerebral ventricle of tyrosine, the amino acid precursor of the catecholamine neurotransmitters, 100% of the animals developed ventricular fibrillation. After tyrosine plus propranolol, a beta-adrenoceptor antagonist, only 9% of pigs developed ventricular fibrillation. Treatment with propranolol alone did not affect the outcome. Catecholamine synthesis in the CNS may be associated with the development of ventricular fibrillation after coronary artery occlusion. PMID- 1510145 TI - Retrograde coronary flow is limited by time-varying elastance. AB - The study examined the influence of left ventricular pressure (PLV) on coronary arterial flow and pressure. In eight anesthetized open-thorax goats with cannulated and artificially perfused left main coronary artery, the PLV was disturbed by aortic occlusions. In the constant pressure perfusion (CPP) protocol the response of systolic arterial inflow on a change in PLV was studied with fixed perfusion pressure and at several perfusion pressure levels. Similarly, in the constant flow perfusion (CFP) protocol the response of systolic perfusion pressure was examined with fixed levels of perfusion flow and repeated for several flow levels. The results show an early systolic response determined by PLV for both protocols. Midsystolic responses were almost absent in the CPP protocol but present in the CFP protocol. At CPP, the effect of a change of PLV on arterial flow in mid systole was only 20% of that on early systolic flow with intact coronary tone and 33% with adenosine-induced vasodilation. At CFP the pulsations in perfusion pressure were 30% of PLV pulsations, both with intact tone and vasodilation; in contrast with the CPP results, no difference for this value was found in different stages of systole. We suggest that stiffness of cardiac muscle determines the influence of PLV on coronary flow. The difference in mid systolic relations between the CPP and CFP protocols is explained by the difference in time constants induced by the perfusion system. The results are best explained by a synthesis between the intramyocardial pump model and the elastance concept. PMID- 1510146 TI - NMR visibility of Pi in perfused rat hearts is affected by changes in substrate and contractility. AB - Nuclear magnetic resonance (NMR) spectroscopy does not always detect the total metabolite content in isolated perfused rat hearts. Alterations in NMR peak areas therefore could be caused by a change either in the metabolite content per se or in its NMR visibility. We have therefore compared the ATP, phosphocreatine (PCr), and Pi content of hearts, as determined by 31P-NMR spectroscopy, with the total, chemically determined ATP, PCr, and Pi contents of the same hearts to determine the fractions, if any, that are NMR invisible under different perfusion conditions. The three perfusion buffers used contained 1) glucose, 2) glucose plus high K+, and 3) pyruvate. Fully relaxed 31P-NMR spectra were collected during the final 10 min of perfusion in each group, and the ATP, PCr, and Pi contents were quantified using methylene diphosphonate as an external standard. The hearts were then freeze-clamped and chemically assayed for ATP, PCr, and Pi. Under all three conditions, the NMR-determined ATP and PCr contents were almost identical to the chemically determined values. However, only a portion of the chemically determined Pi was NMR visible. During perfusion with glucose containing buffer, 39 +/- 8% of the total Pi was NMR visible, and this decreased to 12 +/- 2% (P less than 0.01) during K+ arrest and to 9 +/- 5% (P less than 0.01) during perfusion with pyruvate-containing buffer. In conclusion, whereas the total cellular content of ATP and PCr is always NMR visible during normoxic perfusion, alterations in substrate and contractile status can change the fraction of NMR-visible Pi. PMID- 1510147 TI - Cellular basis of negative inotropic effect of 2,3-butanedione monoxime in human myocardium. AB - 2,3-Butanedione monoxime (BDM) exerts a marked negative inotropic effect and has been shown to have protective actions on human myocardial force production that may be of clinical use. To determine the underlying mechanisms, we studied the effects of BDM on chemically skinned and aequorin-loaded myopathic human myocardium from transplant recipients. Eighteen muscles were chemically skinned with saponin (250 micrograms/ml) and then subjected to activation-relaxation cycles, with and without 5 mM BDM. Contracture force vs. Ca2+ data were fitted to a modified Hill equation, and values for 50% maximal activation (pCa50) and maximal Ca(2+)-activated force (Fmax) were obtained. pCa50 was decreased by 0.2 pCa units, indicating myofilament Ca2+ desensitization, and Fmax was reduced by 48% in 5 mM BDM. A second group of intact muscles (n = 8) was loaded with aequorin to monitor intracellular calcium (Cai2+) transients (peak light) and twitch force in the presence of BDM (1-30 mM). Over a range of 1-20 mM, BDM depressed peak light by 3-49% while force was depressed by 10-82%. This was accompanied by an abbreviation of the duration of the twitch but not of the Cai2+ transient. At a concentration of 30 mM, BDM completely inhibited force generation, but an Cai2+ transient was still present. We conclude that in human myocardium, 5 mM BDM predominantly affects cross-bridge force production and Ca2+ sensitivity and has a less pronounced effect on Cai2+. PMID- 1510148 TI - Acute hypertension and sympathetic stimulation: local heterogeneous changes in cerebral blood flow. AB - The local influence of sympathetic stimulation on the cerebral circulation during acute hypertension was investigated in anesthetized rats. From initial studies, intravenously administered angiotensin II was selected as the pressor agent. Local cerebral blood flow was measured with [14C]iodoantipyrine autoradiography during 1) unilateral electrical stimulation of the superior cervical ganglion plus moderate hypertension [mean arterial blood pressure (MABP) 162 +/- 2 mmHg], 2) unilateral stimulation plus severe hypertension (MABP 177 +/- 4 mmHg), and 3) unilateral preganglionic sympathetic nerve section (denervated) plus severe hypertension (MABP 186 +/- 4 mmHg). During moderate hypertension, blood flow was rather homogeneous and sympathetic stimulation produced modest (7-15%) regionally specific reductions in flow ipsilateral to the stimulation (P less than 0.05). During severe hypertension: 1) focal areas of marked hyperemia occurred throughout the brain, 2) local blood flow was similar within innervated and denervated hemispheres, and 3) with sympathetic stimulation the volume of hyperemic tissue was reduced ipsilaterally and blood flow was decreased by 7-25% in areas of basal ganglia, cerebral cortex, limbic system and thalamus. To conclude, 1) the local cerebral autoregulatory response is highly dependent on whether the area becomes hyperperfused and 2) sympathetic stimulation decreases brain blood flow by modestly reducing local tissue perfusion and by lessening the volume of extreme hyperemia. PMID- 1510149 TI - Mechanism of action of cerebral epoxyeicosatrienoic acids on cerebral arterial smooth muscle. AB - Microsomal preparations of cat brain incubated with [14C]arachidonic acid produced epoxyeicosatrienoic acids (EETs) that eluted with the same retention times as synthetically prepared 5,6-, 8,9-, and 11,12-EETs. These compounds dilated serotonin-preconstricted, pressurized cat cerebral arteries in a dose dependent fashion. Epoxide formation was not found in mitochondrial fractions and was dependent on the presence of NADPH. The maximum effects of 8,9-EET and 11,12 EET were greater than those of 5,6-EET. The cellular basis of this vasodilation was further investigated by examining the effects of 8,9-EET and 11,12-EET on K+ channel activity in vascular muscle cells freshly isolated from cat cerebral arteries. Both 8,9-EET and 11,12-EET increased the frequency of opening, mean open time, and open-state probability of a 98-pS K+ channel recorded in the cell attached mode with 145 mM KCl in the pipette and 4.7 mM KCl in the bath. Blockade of K+ channel activity with tetraethylammonium attenuated the vasodilatory effects of 11,12-EET on serotonin-preconstricted cat cerebral arteries. These results suggest that endogenously formed EETs may participate in local regulation of cerebral blood flow by dilating cerebral arteries through a mechanism that involves activation of K+ channels. PMID- 1510150 TI - ATP formation and energy demand in anoxic heart muscle of the rabbit. AB - In quiescent rabbit papillary muscle at 20 degrees C, the formation of ATP in nitrogen, estimated from the production of lactate, is 21% of that in oxygen. Stimulating the anoxic muscles at 0.2 Hz causes a threefold increase in ATP formation. In this study we want to determine 1) whether glycolytic ATP formation can be increased to a rate that would meet the aerobic ATP demand at rest and 2) what the maximum glycolytic rate attainable through stimulation is. Glycolytic rate is estimated from the amount of lactate produced at various times over 40 min of anoxia. Nucleotides and creatine compounds are also determined. Lactate formation at the onset of anoxia is proportional to stimulus frequency. The amount of lactate formed is correlated to the breakdown of glycogen; glucose is not used. Therefore the amount of glycogen present in the muscle at the onset of anoxia is the main determinant of the amount of ATP formed when oxidative phosphorylation is inhibited. The rate of lactate formation at the onset of anoxia increases from 1.22 mumol.g dry wt-1.min-1 in resting muscles to 18.5 mumol.g dry wt-1.min-1 in 1-Hz-stimulated muscles. This implies that in anoxic myocardium, glycolysis can provide ATP at more than three times the rate found in the muscle at rest in ample oxygen. PMID- 1510151 TI - Pial vessel caliber and cerebral blood flow become dissociated during ischemia reperfusion in cats. AB - The relationship between pial arteriolar caliber and cerebral blood flow (CBF) was examined in 11 cats subjected to reperfusion for up to 120 min after 10 min of global cerebral ischemia induced by four-vessel occlusion and systemic hypotension. Thirty minutes after reperfusion CBF, as assessed by radiolabeled microsphere injection, had increased to 588% of control in middle cerebral artery (MSEC) cortical gray matter territory. The caliber of MSEC pial arterioles measured using the closed cranial window technique (greater than 33 to less than 213 microns) increased to 172% of baseline. By 60 min of reperfusion, CBF was 76% of basal levels, but pial arterioles remained 133% of baseline. After 120 min, CBF approximated baseline values, but pial dilatation persisted (115% of control). Intracranial pressure measurements did not differ significantly from resting values. At 45 min and beyond, total cerebrovascular resistance did not differ from resting values. The coexistence of vasodilatation within pial arterioles and normal blood flow in cortical gray matter indicates that pial vessels (greater than 33 microns) cannot be responsible for normal blood flow restoration following postocclusive hyperemia. Resistance during the posthyperemic phase must be increased selectively within parenchymal vessels to account for normal total cerebrovascular resistance, pial vessel dilatation, and normal-low parenchymal blood flow. Whether obstruction rather than vasoconstriction explains the resistance changes within intraparenchymal vessels remains for further study. PMID- 1510152 TI - Interstitial adenosine with dipyridamole: effect of adenosine receptor blockade and adenosine deaminase. AB - Dipyridamole is proposed to increase coronary blood flow (CBF) by inhibition of adenosine uptake into cells, resulting in an increase in interstitial fluid (ISF) adenosine and an adenosine-mediated vasodilation. The purpose of this study was to determine the changes in CBF and ISF adenosine, inosine, and hypoxanthine during dipyridamole infusion in the absence or presence of adenosine receptor blockade or adenosine deaminase. To sample cardiac ISF, cardiac microdialysis probes were implanted in the left ventricular myocardium of chloralose-urethan anesthetized dogs and perfused with Krebs-Henseleit buffer. The metabolite concentration in the effluent dialysate was used as an index of intramyocardial ISF metabolite concentration. In response to dipyridamole, CBF and dialysate adenosine concentration increased 4.4-fold and 2.2-fold, respectively, whereas dialysate inosine was unchanged and dialysate hypoxanthine decreased 50%. Adenosine receptor blockade, achieved by intracoronary 8-(p sulfophenyl)theophylline infusion, attenuated the increase in CBF induced by dipyridamole without changing dialysate adenosine concentration. Adenosine deaminase fully attenuated the dipyridamole-induced increases in CBF and dialysate adenosine. These results demonstrate that dipyridamole increases ISF adenosine in the dog and suggest that adenosine is the sole mediator of dipyridamole-induced coronary vasodilation. PMID- 1510153 TI - Effects of arterial hypertension on myocardial recovery after ischemic injury. AB - Although improved surgery, angioplasty, and thrombolysis have made early revascularization of ischemic myocardium commonplace, the effects of arterial hypertension on myocardial recovery remain unclear. Therefore eight conscious dogs were instrumented to measure left ventricular transmural pressure and myocardial segment length in the left anterior descending (LAD) coronary distribution. Reversible ischemic injury was produced by two 15-min LAD occlusions separated by 4 days of reperfusion, with each dog randomly receiving either phenylephrine or placebo infusion for 30 min beginning 1 h after reperfusion. With ischemia, systolic myocardial performance fell to 14.3 +/- 3.7% of control and required greater than 48 h to recover. Compared with placebo, phenylephrine significantly depressed recovery of systolic function assessed by systolic shortening (57 +/- 12 vs. 85 +/- 13% control) or the area under the stroke work vs. end-diastolic length relationship (62 +/- 14 vs. 93 +/- 7% control) (both P less than 0.05). These data imply that ischemically injured myocardium is highly sensitive to arterial hypertension and that ventricular loading is a major determinant of the rate of myocardial recovery. PMID- 1510154 TI - Focal cortical distribution of blood flow and brain pHi determined by in vivo fluorescent imaging. AB - A technique was developed for panoramic imaging of intracellular focal brain pH (pHi) and focal cortical blood flow to measure the pattern of changes in these parameters during arterial PCO2 (PaCO2) and arterial PO2 (PaO2) alterations. Eleven overnight-fasted New Zealand White rabbits were operated and studied under 2.0 and 1.0% halothane anesthesia, respectively. The exposed cortex was imaged by a 512 x 512 pixel image intensifier system with a resolution of 10 microns2/pixel. Focal brain pHi and focal cortical blood flow were measured by umbelliferone fluorescence. The mean focal cortical blood flow was 49 +/- 4.5 ml.100 g-1.min-1, and focal brain pHi was 7.05 +/- 0.02 during normocapnia. At a stable PaCO2, focal cortical blood flow and focal brain pHi within 10 microns of surface-conducting vessels were 2-50% greater and 0.02 pH units lower than that observed in the border-zone regions between vessels. Focal cortical blood flow demonstrated a significant heterogeneity of 51% among various cortical regions, despite a stable PaCO2. Alternatively, focal brain pHi was homogeneous, varying no more than 0.05 pH units. These results demonstrate the dependence of focal cortical blood flow on topical locations from surface conducting vessels and the tight regulation of brain pHi. PMID- 1510155 TI - Agonist-induced [Ca2+]i waves and Ca(2+)-induced Ca2+ release in mammalian vascular smooth muscle cells. AB - Focal application of vasopressin to cultured vascular smooth muscle cells (A7r5 cells) elicits first a localized increase of intracellular Ca2+ concentration ([Ca2+]i) and then a wave of elevated [Ca2+]i that propagates at constant velocity throughout the cell. The cellular mechanisms of such complex spatiotemporal patterns of [Ca2+]i are of interest because they are involved fundamentally in cellular signal transduction in many types of cells. Vasopressin evoked a [Ca2+]i transient even in the absence of extracellular Ca2+, and intracellular perfusion with heparin completely blocked the response to vasopressin stimulation. Therefore the initial response to vasopressin reflects release of Ca2+ from an intracellular myo-inositol-1,4,5-trisphosphate (IP3) sensitive Ca2+ store. We tested four hypotheses on how a localized increase in [Ca2+]i propagates as a [Ca2+]i wave throughout the entire cell: the hypotheses distinguished 1) whether IP3 or Ca2+ is the primary intracellular messenger that diffuses, and 2) whether positive feedback on the release of intracellular Ca2+ (Ca2+i) is involved (further release of Ca2+ through activation of phospholipase C by Ca2+ and increased production of IP3 or by Ca(2+)-induced Ca2+ release). The results of various experimental interventions, which included probing Ca2+i stores (heparin, caffeine, and ryanodine), were compared with predictions from mathematical models for intracellular diffusion, release, and uptake of Ca2+. We conclude that in A7r5 smooth muscle cells, which have been stimulated focally with vasopressin, Ca2+ is released initially by IP3. The localized increase in [Ca2+]i then propagates throughout the cell as a [Ca2+]i wave. Ca2+ activates its own release, through Ca(2+)-induced release of Ca2+, by diffusing to distant Ca(2+)-release sites. PMID- 1510156 TI - Effect of methylene blue on vasoreactivity in dog lung. AB - We examined the effect of methylene blue (MB), a putative inhibitor of guanylate cyclase (GC) activation by endothelium-derived relaxing factor (EDRF) and nitrovasodilator compounds, on vascular tone and reactivity to vasoactive substances in the isolated, blood-perfused canine lower left lung lobe. Lobar vascular resistance was partitioned into arterial and venous segments by venous outflow occlusion. Because MB did not alter vasoconstriction to either serotonin or acetylcholine (P greater than 0.05) except after cyclooxygenase inhibition (COI), we determined the effectiveness of MB as an inhibitor of GC activation by nitrovasodilators. Lobes were given graded bolus doses of nitroglycerin (GTN), sodium nitroprusside (SNP), and bradykinin (BK) at baseline vascular tone, after COI, and after vascular tone was raised by either U-46619, a thromboxane analogue, or MB infusion. GTN and BK but not SNP induced dose-dependent vasodilation when vascular tone was raised by U-46619. However, when vascular tone was increased to a similar level by 30 mg MB and 0.5 mg/min infusion, vasodilation to GTN, SNP, and BK was enhanced from U-46619 infusion. In contrast to MB, NG-nitro-L-arginine, a putative inhibitor of EDRF synthesis, diminished vasodilation to BK in cyclooxygenase-inhibited lobes with elevated vascular tone. Because MB potentiated vasodilation to GTN, SNP, and BK, it is questionable whether MB is an effective inhibitor of vasodilation to nitrovasodilators or BK in the isolated, blood-perfused canine lung. PMID- 1510157 TI - Time-varying wall stress: an index of ventricular vascular coupling. AB - Previous work in the isolated heart and intact circulation has suggested that the relationship between wall stress and time during left ventricular (LV) ejection is linear and that the slope, which will be referred to as time-varying wall stress, increases in response to augmentation in afterload. However, the etiology of the increase in slope has not been determined in an intact animal. Magnetic resonance imaging coupled with high-fidelity LV pressure measurement using a nonferrous catheter-tip manometer generates a detailed assessment of wall stress in an animal model where the thorax and pericardium have never been disturbed. Accordingly, six anesthetized dogs were studied during autonomic blockade with atropine and propranolol during angiotensin infusion, producing three widely disparate left ventricular systolic pressures (87 +/- 7 vs. 124 +/- 13 vs. 152 +/ 10 mmHg, P less than 0.001). Time-varying wall stress did not change from low to medium load (-42.4 +/- 9.5 to -27.3 +/- 22.3 g.cm-2.ms-1) but increased significantly at high load (-21.7 +/- 14.9 g.cm-2.ms-1, P less than 0.05). Analysis of the relative contribution of pressure, chamber radius, wall thickness, and long-axis dimension to the changes in time-varying wall stress demonstrated only the pressure component to change its relative contribution at medium (P less than 0.001) and high load (P less than 0.001). Therefore, we conclude that the increase in time-varying wall stress results from augmentation of pressure in the latter one-half of systole that is incompletely offset by shortening and wall thickening.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1510158 TI - Stretch-induced depolarizations as a trigger of arrhythmias in isolated canine left ventricles. AB - Transient diastolic stretch of the left ventricle predictably elicits arrhythmias. To investigate the mechanism of such stretch-induced arrhythmias, monophasic action potentials were recorded from six blood-perfused isolated canine left ventricles with an epicardial contact electrode. Stretch-induced arrhythmias were elicited using a computerized servo-pump system that increased left ventricular volume for 250 ms during early diastole. Depolarizations that coincided with the onset of stretch were observed that always preceded the stretch-induced arrhythmia. As stretch volume (delta V) increased from 10 to 30 ml, the amplitude of the stretch-induced depolarization increased progressively and the probability of eliciting an arrhythmia rose from 30 to 94%. To exclude motion artifact, additional recordings were made after the heart was depolarized by increasing the perfusate K+ concentration to 154 mM (K arrest). After K arrest, the stretch-induced depolarizations were reduced by 95% or more (P less than 0.05) at all stretch volumes. Thus the change in monophasic action potential signal during transient diastolic stretch reflects actual depolarization of the myocardium with negligible motion artifact. When the stretch-activated channel blocker, Gd3+ (10 microM), was administered, which produces potent inhibition of stretch-induced arrhythmias in our model, the stretch-induced depolarizations were substantially reduced in magnitude. Our results show that as diastolic stretch increases, stretch-induced depolarizations become larger and reach threshold potential more often; consequently, the probability of eliciting a stretch-induced arrhythmia increases. This mechanism of arrhythmogenesis may be particularly important in patients with regionally or globally dilated left ventricles. PMID- 1510159 TI - Magnesium affects excitation, conduction, and contraction of isolated mammalian cardiac muscle. AB - An increase of extracellular Mg concentration, [Mg]o, reduced myocardial excitability and conduction without affecting the resting membrane potential or action potential configuration in ventricular myocytes and papillary muscles from a number of mammalian species. Although there was a small increase of specific membrane resistance and no change to intracellular resistivity, the threshold voltage was shifted to depolarized potentials. Thus loss of excitability can be explained by a shift of the activation of inward currents to depolarized potentials, and reduced conduction velocity is due solely to a diminution of local circuit currents. Mgo also was negatively inotropic, the magnitude of this effect being species dependent. Raised [Mg]o caused a small increase of intracellular [Mg] with a small decrease of intracellular [Na+], did not affect intracellular pH, and attenuated the intracellular Ca2+ transient associated with cell shortening in rat (but not rabbit) myocytes. An increase of [Mg]o reduced the magnitude of the voltage-dependent inward Ca2+ current, ICa, in rat and rabbit myocytes, and the activation curve of ICa was shifted to more depolarized potentials. A scheme to account for the negative inotropic effect of Mg is presented. PMID- 1510160 TI - Inhibition of bovine retinal microvascular pericyte proliferation in vitro by adenosine. AB - Adenosine acts on bovine retinal microvascular pericytes through one or more adenosine receptor subtypes present on the cell surface. Retinal pericytes cultured in medium containing adenosine at concentrations from 10(-6) to 10(-4) M showed significant reduction in proliferation following several days in vitro compared with control cultures. The effects of adenosine were mimicked by polyadenylic acid and inhibited by 8-phenyltheophylline, indicating involvement of a cell surface receptor. Metabolites of adenosine had no effect on pericyte proliferation. An A2 adenosine receptor-specific analogue also inhibited pericyte growth, suggesting that inhibition by adenosine is mediated by A2-receptors and might involve a transient increase in adenosine 3',5'-cyclic monophosphate levels. The results of the present study demonstrate that in addition to demonstrated stimulatory effects on capillary endothelial cells, adenosine also has a direct inhibitory effect on retinal pericytes. We hypothesize a dual function of adenosine within the capillary wall resulting in loss of inhibition of endothelial cells and suggest a role for this nucleoside in pathological neovascularization processes such as proliferative diabetic retinopathy. PMID- 1510162 TI - Regional cerebral blood flow and tissue oxygenation during hypocarbia in geese. AB - Very low arterial CO2 tension (PaCO2) experienced by birds during high-altitude flight may result in cerebral vasoconstriction and reduced cerebral O2 delivery. To examine this possibility, we measured regional cerebral blood flow (CBF) and tissue PO2 in pentobarbital-anesthetized geese (Anser domesticus). Twenty-five micrometer Teflon-coated platinum electrodes for H2-clearance measurements of local blood flow or tissue PO2 were implanted in the cerebral cortex in 11 geese. Tissue H2 and O2 were measured by voltage clamping the electrodes at +0.30 and 0.5 V, respectively. Washout kinetics of H2 gas administered via unidirectional lung ventilation was used to calculate local blood flow for those electrodes exhibiting one- or two-compartment washout kinetics of H2 (128 of 296 washouts in 31 electrodes). PaCO2 was controlled between 8 and 55 mmHg by altering pulmonary gas flow or by adjusting inspired PCO2. CBF decreased as PaCO2 fell from 50 to 20 mmHg but did not decrease further as PaCO2 was reduced below 20 mmHg. CBF was uniformly distributed in different regions of the cortex. Despite the plateau in CBF during severe hypocapnia, tissue PO2 continued to decline as PaCO2 fell below 20 mmHg. Severe alkalosis may limit cerebral O2 delivery in birds during high altitude flight. PMID- 1510161 TI - Flow modulates coronary venular permeability by a nitric oxide-related mechanism. AB - This study demonstrates that flow velocity modulates coronary venular permeability to albumin. Apparent permeability coefficients of albumin (Pa) were measured in isolated cannulated coronary venules ranging from 30 to 70 microns in diameter. Hydrostatic and oncotic pressures were controlled while the intraluminal flow velocity was varied. Pa at an intraluminal hydrostatic pressure of 12 cmH2O and a flow velocity of 7 mm/s was 4.01 +/- 0.53 x 10(-6) cm/s. Increasing flow velocity to 10 and 13 mm/s augmented the permeability by 33 +/- 14 and 48 +/- 14%, respectively. The nitric oxide synthase inhibitor, NG monomethyl-L-arginine (L-NMMA) (10(-5) M), decreased baseline Pa and abolished the flow-induced permeability changes. Administration of L-arginine (3 x 10(-3) M), a physiological precursor of nitric oxide which reverses the effect of L NMMA, restored the relationship between flow and permeability. From these results we conclude that 1) flow velocity should be considered as a physical force that potentially modulates permeability of venular exchange vessels in the heart and 2) flow modulates coronary venular permeability via the production of nitric oxide. PMID- 1510163 TI - Betaine transport in the gill of a marine mussel, Mytilus californianus. AB - The integumental epithelium of Mytilus californianus gill accumulates amino acids directly from seawater against chemical gradients exceeding 10(7) to 1. In the present report, we confirm the presence of betaine in Mytilus tissue and identify a transport process in the gill for this organic osmolyte. Betaine content of gill tissue from animals acclimated to 100% seawater (980 mosM) was 45 mmol/kg wet wt, similar to that of taurine (53 mmol/kg). The kinetics of betaine uptake were adequately described by the Michaelis-Menten equation, with a Kt of 6 microM and Jmax of 7 mumol.g-1.h-1. Betaine transport was inhibited by L-proline and related structural analogues, and by alanine. L-Proline transport, which involves both high- and low-affinity pathways, was partially inhibited by betaine. The low affinity proline pathway transports lysine. Betaine and L-lysine showed no reciprocal inhibitory interactions. This pattern of structural specificity suggested that betaine transport in the gill is confined to the alanine-proline pathway. Uptake of 0.5 microM betaine into gills was inhibited by 97% when Na+ in seawater was replaced with Li+. Activation of betaine transport in the gill was a near-linear function of the external Na+ concentration up through 100% artificial seawater (ASW, 425 mM Na+). Acute exposure of the gill to 60% ASW inhibited betaine uptake by 83%. Maintenance of normal osmotic concentration (980 mosM, by addition of mannitol to 60% ASW) reduced inhibition to 31%, similar to the level predicted from the availability of Na+.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1510164 TI - Preferential retention of linoleic acid-enriched triacylglycerols in liver and serum during fasting. AB - Fasting has been reported to quantitatively increase linoleic and arachidonic acids in liver triacylglycerols, but the origin and mechanism of this change are unknown. The changes in long-chain fatty acids and triacylglycerol species of liver, serum, adipose tissue, and heart were therefore examined during a period of 24- or 48-h fasting in the rat. In liver and serum triacylglycerols, fasting resulted in a quantitative increase in arachidonic, stearic, linoleic, alpha linolenic, and docosahexaenoic acids but a decrease in oleic, palmitic, and palmitoleic acids. After fasting, oleic acid was depleted the most from liver and serum triacylglycerols followed by palmitoleic and palmitic acids. Triacylglycerol species containing palmitic, palmitoleic, and oleic acids were depleted the most from liver and serum during fasting. Linoleic acid-enriched triacylglycerol species were proportionally and, in some cases, quantitatively increased in liver and serum triacylglycerols during fasting. Net retention of triacylglycerol species with a total acyl carbon number of 56 or 58 in the liver and 60 in serum was also observed during fasting. Selective retention of triacylglycerol species did not occur in the heart or perirenal or epididymal adipose tissue during fasting. Tissue phospholipid fatty acids were largely unaffected by fasting. Our data suggest that during fasting, long-chain fatty acids released from adipose tissue are differentially utilized and hepatic triacylglycerol species are remodeled, permitting optimal tissue composition of essential fatty acids, particularly linoleic acid. PMID- 1510165 TI - Relationship between blood O2 content and catecholamine levels during hypoxia in rainbow trout and American eel. AB - Plasma catecholamine levels and arterial blood respiratory variables were monitored in rainbow trout (Oncorhynchus mykiss) and American eel (Anguilla rostrata) acutely exposed (30 min) to graded levels of external hypoxia [water PO2 (PWO2) 20-90 Torr]. The experiments were designed to evaluate the factors controlling catecholamine mobilization in hypoxic fish and to elucidate the basis of marked interspecific differences. In trout, plasma catecholamine levels were unchanged when PWO2 remained above 50 Torr but increased markedly when PWO2 was lowered below this value; the predominant catecholamine released into the circulation was epinephrine. In eel, there was no such obvious PWO2 threshold for catecholamine release although plasma levels were consistently elevated above baseline only at PWO2 less than 35 Torr. The magnitude of the catecholamine release in eel was approximately an order of magnitude less than in trout. Unlike in trout, there was no increase in the plasma epinephrine-to-norepinephrine concentration ratio. During hypoxia, the relationship between arterial blood PO2 (PaO2) and PWO2 was similar in both species and thus could not explain the differences in the PWO2 thresholds for catecholamine release. In trout, the calculated PaO2 thresholds for catecholamine release were 25.3 (epinephrine) and 20.5 Torr (norepinephrine) whereas in eel the corresponding values were 12.5 and 11.6 Torr, respectively. These PaO2 thresholds were in good agreement with the in vivo values for PaO2 at half-maximal hemoglobin (Hb)-O2 saturation (P50) for trout and eel blood of 22.9 and 11.1 Torr, respectively. Thus both species displayed essentially equivalent catecholamine release thresholds when expressed in terms of arterial blood O2 content corresponding to approximately 45-60% Hb-O2 saturation. PMID- 1510166 TI - Underfeeding and body weight regulation in normal-weight young men. AB - The mechanisms of energy regulation invoked by moderate dietary restriction were investigated in seven healthy young men of normal body weight leading unrestricted lives. Following a baseline period of weight maintenance, subjects were underfed by 806 +/- 162 (mean +/- SE) kcal/day for 21 days. Changes in total energy expenditure (TEE) and resting energy expenditure (REE) and subsequent voluntary nutrient intakes were measured. The REE, averaged for fasting and fed states, decreased during underfeeding by 100 +/- 29 kcal/day (P less than 0.01). TEE decreased nonsignificantly by 296 +/- 170 kcal/day, equivalent to an average of 37% of the decrease in energy intake. Body energy stores were estimated to decrease by 510 +/- 172 kcal/day (P less than 0.03), thus compensating for 63% of the dietary energy deficit on average. Voluntary energy intake following dietary restriction increased above the initial amount required for body weight maintenance, was proportional to the weight loss during underfeeding (P less than 0.03), and was associated with a rapid regain of weight lost during underfeeding. These results indicate that energy balance is regulated by adaptive variations in both energy intake and energy expenditure in normal-weight young men leading unrestricted lives but do not support the hypothesis that energy-wasting mechanisms contribute substantially to body energy regulation. PMID- 1510167 TI - Nucleus tractus solitarius and control of blood pressure in chronic sinoaortic denervated rats. AB - To determine the role of the nucleus tractus solitarius (NTS) in the tonic maintenance of arterial pressure (AP) following chronic baroreceptor denervation, the present study examined the effect of inhibition of the NTS on AP in chronic sinoaortic denervated (SAD) and control rats. One to two weeks after complete SAD (no residual arterial baroreceptor reflexes) mean AP was not significantly different from that of control rats. Bilateral microinjections of muscimol and lidocaine into the NTS markedly increased AP in alpha-chloralose-anesthetized control rats. However, microinjections of these neuroinhibitory drugs had no effect on AP in SAD rats. Similarly, 1 h after bilateral destruction of the NTS conscious control rats were hypertensive, while AP in SAD rats was not changed. Plasma levels of vasopressin (VP), which were also elevated in control rats 1 h after NTS lesions, were not significantly altered in SAD rats. These results demonstrate that inhibition of the NTS has no effect on AP or plasma levels of VP in chronic SAD rats. This suggests neither the NTS nor afferents to the NTS supply a tonic inhibitory influence on AP after chronic baroreceptor denervation. PMID- 1510168 TI - Effects of hypoxia and ambient temperature on gaseous metabolism of newborn rats. AB - Whole body metabolic rate was measured by open-flow respirometry in 2-day-old rats at ambient temperatures (Ta) between 40 and 15 degrees C, changed at a rate of 0.5 degrees C/min, during normoxia or hypoxia (10% inspired O2). In normoxia, the thermoneutral range was found to be very narrow, at around 33 degrees C, suggesting a limited effectiveness in the mechanisms controlling heat dissipation. At lower or higher Ta, metabolism was at first increased; this increase could be maintained for at least 30 min at 30 and 35 degrees C, i.e., slightly below or above thermoneutrality, but it was not maintained at lower Ta. The metabolic response to Ta was not sufficient to maintain body temperature (Tb). In hypoxia, at all Ta, oxygen consumption (VO2) was consistently less than in normoxia and was linearly related to Ta (Q10 approximately 1.4). The rat's specific heat was 4 J.g-1.degrees C-1, and the time constant of passive heat exchange was 2.2 +/- 0.5 min; from these values it was calculated that the normoxic VO2 of the 2-day-old rat could be per se sufficient to maintain Tb of 35 36 degrees C at Ta of 33 degrees C, while at lower Ta the metabolic response could not be adequate to maintain Tb. In hypoxia, Tb was directly dependent on Ta.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1510169 TI - Entrainment of respiratory rhythm by periodic lung inflation: effect of airflow rate and duration. AB - In anesthesized, paralyzed, and mechanically ventilated rabbits, the rate and duration of airflow were varied to investigate the effect on the central respiratory rhythm during 1:1 entrainment (1 phrenic nerve burst for 1 pump inflation). Our results showed that 1) the largest range of 1:1 entrainment was obtained with the longest inflation durations associated with the lowest flow rates and 2) both inspiratory (TI) and expiratory (TE) durations (as estimated by the period of phrenic nerve activity and phrenic nerve silence, respectively) increased when total respiratory duration (TT = TI+TE) increased. The phase relationships we studied were DI (the time elapsing between the onset of phrenic activity and the beginning of pump inflation) and DE (the time between the end of phrenic activity and the end of pump inflation). Both DI and DE increased when the total ventilatory period increased. However, for constant ventilatory period, DI changed with the rate and duration of airflow, whereas DE remained constant. In addition, under these conditions, TI, TE, and the integrated phrenic nerve activity remained constant independently of airflow rate and duration. The present results are discussed with regard to the pulmonary receptors (slowly and rapidly adapting receptors and C fibers) that are stimulated during mechanical ventilation, and hypotheses are drawn regarding their possible contribution to rhythm generation and the mechanism through which they may act. PMID- 1510170 TI - Carotid baroreflexes and plasma vasopressin in humans during head-up tilt. AB - To investigate the influence of carotid baroreflexes on plasma arginine vasopressin (AVP) in humans, eight healthy males underwent two sessions of passive head-up tilt to 60 degrees for 15 min each. During one of the sessions (sequence randomized), carotid baroreflexes were simultaneously stimulated by static neck suction of 23 +/- 1 mmHg during the whole period of head-up tilt. Only subjects who did not develop presyncopal symptoms during head-up tilt were included. Head-up tilt increased AVP significantly from 1.0 +/- 0.3 to 4.2 +/- 1.3 pg/ml (P less than 0.05). In contrast to this, AVP did not at any point in time increase significantly during head-up tilt when neck suction was applied. Plasma renin activity and heart rate were unaffected by neck suction, whereas mean arterial pressure and central venous pressure decreased. We conclude that the moderate but significant increase in plasma AVP during nonhypotensive head-up tilt is in part mediated by deloading of carotid baroreceptors induced by the acute fall in hydrostatic pressure at the level of the carotid sinus. PMID- 1510171 TI - Neural regulation of the vas deferens in the rat: an electrophysiological analysis. AB - Electrophysiological analysis of the neural control of the vas deferens was performed in urethan-anesthetized rats. Intraluminal distension (0.2 ml/min) or electrical stimulation of hypogastric (threshold 1-5 V, 20 Hz) and pelvic nerves (2-5 V, 20 Hz) produced contractions of the vas deferens. Distension-evoked contractile activity was not abolished by nicotinic ganglionic blockade or ipsilateral hypogastric and pelvic nerve transection. Contractions following hypogastric nerve stimulation were abolished by prazosin, while pelvic nerve evoked responses were partially blocked by atropine. Hypogastric nerve, pelvic nerve, and sympathetic chain stimulation evoked volleys with latencies of 10-30 ms in vasal nerves. Crude estimates for conduction velocities for these responses (less than 0.5 m/s) corresponded to activation of unmyelinated C-fibers. Stimulation of the dorsal nerve of the penis (DNP) (10-16 V, 10-40 Hz) or administration of 5-methoxy-N,N-dimethyltryptamine, both of which produce seminal emission, elicited reflex discharges in nerves to the vas deferens. Hypogastric nerve but not pelvic nerve transection abolished both spontaneous and evoked (105 to 380-ms latency) reflex activity. These experiments provide insight into the organization of afferents in the DNP and efferents conveyed by autonomic pathways that regulate male reproduction. PMID- 1510172 TI - Weakness of short-term synchronization among respiratory nerve activities during fictive vomiting. AB - In decerebrate, paralyzed cats, phrenic (PHR) and lumbar abdominal (ABD) nerve discharges during both neural respiration and fictive vomiting (FV) were subjected to spectral and coherence analyses. During respiration, PHR discharge exhibited high-frequency oscillation (HFO), manifested as a narrow spectral peak (range 57-90 Hz) in autospectra and left-right coherence spectra. During FV, the following occurred: 1) the HFO peak disappeared and was replaced by a broad peak with higher modal frequency (range 84-120 Hz), indicating elimination of inputs from the medullary inspiratory pattern generator. 2) Left-right PHR coherence spectra had no distinct peaks, indicating that correlations between opposite PHR discharges were now not frequency specific. 3) Although ABD and PHR autospectra were similar, PHR-ABD coherences were near zero, indicating lack of common inputs on a short time scale. 4) Nonzero coherences between ABD nerves were confined to ipsilateral pairs. Thus coherence analysis indicates that the outputs of the vomiting pattern generator are temporally dispersed on a short time scale and are not necessarily common to different motoneuron populations. PMID- 1510174 TI - Daily torpor in the absence of the suprachiasmatic nucleus in Siberian hamsters. AB - Siberian hamsters express torpor spontaneously after several weeks of exposure to short days. In long days, torpor is expressed only when food intake is restricted. Hamsters maintained in a long photoperiod (16 h light/day) at 15 degrees C expressed daily torpor during food restriction both before and after bilateral ablation of the suprachiasmatic nucleus (SCN). Hamsters housed in short days (8 h light/day, ambient temperature 15 degrees C) and fed ad libitum displayed torpor before, but not after, ablation of the SCN (SCNX). Torpor was reinstated in all short-day SCNX hamsters during postoperative food restriction and persisted in several animals even after ad libitum feeding was reinstated. Torpor was entrained to the light-dark cycle in both long- and short-day hamsters preoperatively but appeared to occur in a temporally random fashion in SCNX animals. SCNX hamsters, unlike control animals, displayed multiple torpor bouts per 24 h. The SCN is not essential for the expression of torpor but plays a crucial role in its temporal organization. PMID- 1510173 TI - Divergent effects of intravenous GSH and cysteine on renal and hepatic GSH. AB - There is a growing interest in the therapeutic use of sulfhydryls. To assess the effect of glutathione (GSH) and cysteine on the cellular thiol status, thiols were administered intravenously to rats in doses ranging from 1.67 to 8.35 mmol/kg with and without pretreatment with 4 mmol/kg buthionine-[S,R]-sulfoximine (BSO), an inhibitor of GSH synthesis. One hour after administration of 1.67 mmol/kg GSH, the concentration of GSH rose from 5.2 +/- 1.0 to 8.4 +/- 0.9 mumol/g and from 2.5 +/- 0.5 to 3.7 +/- 0.7 mumol/g in liver and kidneys, respectively. After 8.35 mmol/kg, hepatic GSH did not increase further, but renal GSH rose to 6.7 +/- 1.8 mumol/g. Infusion of cysteine increased hepatic GSH to the same extent as intravenous GSH, but renal GSH did not increase after 1.67 mmol/kg and even significantly decreased to 0.6 +/- 0.2 mumol/g after 8.35 mmol/kg. In the presence of BSO, GSH resulted in a significant increase in renal but not hepatic GSH, suggesting that the kidneys take up intact GSH and indicating that the increment in hepatic GSH was due to de novo synthesis. The present data show that hepatic GSH can be markedly increased in vivo by increasing the supply of cysteine. Measurements of hepatic cysteine indicate that up to a concentration of approximately 0.5 mumol/g cysteine is a key determinant of hepatic GSH, such that the physiological steady-state concentration of GSH in the liver appears to be mainly determined by the availability of cysteine. At higher concentrations GSH does not increase further, possibly due to feedback inhibition of GSH synthesis or increased efflux.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1510176 TI - Arterial chemoreceptor input to nucleus tractus solitarius. AB - The arterial chemoreceptors play an important role in the reflex regulation of blood pressure and respiration. To investigate the initial integration of chemoreceptor inputs within the central nervous system, intracellular recordings were obtained in pentobarbital-anesthetized, paralyzed, and mechanically ventilated cats, from 58 cells within the nucleus of the tractus solitarius (NTS) that were depolarized by activation of the ipsilateral carotid body chemoreceptors. Close arterial injection of less than 100 microliters CO2 saturated bicarbonate evoked depolarizations of membrane potential with amplitudes of 2.2-4.6 mV and durations of 1.8-6.7 s in 46 cells. In 12 cells, activation of the carotid body chemoreceptors evoked a depolarization hyperpolarization sequence. Electrical stimulation of the carotid sinus nerve (500 microA, 0.2 ms) evoked EPSPs [mean latency 6.4 +/- 0.5 (SE) ms; range 2.1 18.4 ms] in 46 cells and EPSP-IPSPs (7.3 +/- 0.8 ms; range 4.2-12.4 ms) in 12 cells. The distribution of EPSP latencies exhibited two peaks, one in the 2- to 4 ms range and another in the 7- to 8-ms range. Twenty-nine chemoreceptive cells were tested for the presence of convergent inputs from the ipsilateral carotid sinus baroreceptors. No evidence was found of a convergent postsynaptic inhibitory input from the baroreceptors within the NTS; however, seven cells were found that received an excitatory input from the baroreceptors. The observation that NTS neurons do not integrate chemoreceptor afferent inputs in a homogeneous manner suggests that the multiplicity of NTS unit responses might be related to the specific reflex function of an individual cell (e.g., vagal or sympathetic outflow, respiration).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1510175 TI - Catecholamine depletion of the diagonal band reduces baroreflex inhibition of supraoptic neurons. AB - In the rat, neurons in the diagonal band of Broca (DBB) participate in baroreceptor-induced depression of spontaneous activity of vasopressin neurons in the supraoptic nucleus (SON). The present study examined the role of the catecholaminergic innervation of the DBB in this response. Male rats were anesthetized with pentobarbital (50 mg/kg ip) and stereotaxically injected in the DBB with either vehicle (2 microliters), 6-hydroxydopamine (6-OHDA; 4 micrograms/2 microliters), or 6-OHDA preceded 20 min earlier by desimipramine (25 mg/kg ip), a norepinephrine uptake inhibitor. Two weeks later, the rats were reanesthetized and a transpharyngeal approach was used for extracellular recording from SON neurons. In vehicle-injected controls, baroreceptor stimulation produced by brief increases in blood pressure from metaraminol injections (10 micrograms/10 microliters iv) transiently arrested the spontaneous activity of 24 of 24 phasically active neurons tested. Sixty-three percent of the vasopressin neurons were not affected by comparable increases in blood pressure in 6-OHDA-treated rats, and the norepinephrine content of the DBB was significantly reduced. In experiments with desimipramine-pretreated rats, 92% of the vasopressin neurons were silenced by increases in blood pressure while the norepinephrine content of the DBB was not affected. Thus the noradrenergic innervation of DBB appears to participate in the baroreceptor sensitivity of SON vasopressinergic neurons. PMID- 1510177 TI - Vasopressin and fetal cerebrovascular regulation. AB - Vasopressin (AVP) may increase cerebral blood flow (CBF) during hypoxemia by selective dilatation of cerebral vessels via endothelium-derived relaxing factor (EDRF) release. To test whether this action is relevant in the fetus, we produced isocapnic hypoxemia in halothane-anesthetized pregnant ewes. Fetal infusion of a V1 AVP antagonist reduced by 55% the increase in CBF during fetal hypoxemia. To test the role of this response during development, we examined the response to AVP in intact and endothelium-denuded femoral and basilar arterial rings in vitro from fetal, newborn, and adult sheep. AVP constricted femoral rings in an endothelium-independent manner, with increased potency in newborn and fetal compared with adult rings. AVP relaxed basilar rings in an endothelium-dependent manner, which was unaffected by indomethacin treatment, with increased potency in newborn and adult compared with fetal rings. We conclude that fetal cerebral vascular endothelium is functional and responsive to AVP and that circulating AVP during fetal hypoxemia contributes to increased CBF via this effect. PMID- 1510178 TI - Bile is essential for lipid assimilation in Leach's storm petrel, Oceanodroma leucorhoa. AB - A tritium-labeled glycerol triether was tested as a non-absorbable lipid marker for studies of neutral lipid absorption in normal and cholestryamine-induced steatorrhic chicks of Leach's storm petrel (Oceanodroma leucorhoa). Absorption of triacylglycerol and wax ester (96 +/- 4.2 and 94 +/- 2.1%, respectively) in normal chicks was indistinguishable. Absorption of neutral lipids decreased with increasing quantities of resin, and with the highest dosage (14% wt/wt) less than 30% of dietary lipids were assimilated. The concentration of bile salts (greater than 500 mM) in the gallbladder of Leach's storm petrel is among the highest recorded. The bile salts are predominantly taurine conjugates of chenodeoxycholate and cholate. Biliary cholesterol levels are within the range observed in humans although biliary phospholipid levels are lower and triglyceride levels are higher. Extensive retrograde movement of duodenal contents and biliary secretions to the gizzard and proventriculus were found. Although similarities in fat and bile salt assimilation exist between seabirds and mammals, there do exist differences that make non-polar lipid assimilation (i.e., wax esters) more efficient in seabirds. PMID- 1510179 TI - Purification and biological activity of alligator bradykinin. AB - Incubation of plasma form the alligator (Alligator mississipiensis) with glass beads in the presence of a kininase inhibitor resulted in the activation of the kallikrein-kinin system and generation of bradykinin-like immunoreactivity. The kinin peptides were purified to homogeneity and were shown to comprise [Thr6] bradykinin and des-Arg9[Thr6]bradykinin in the molar ratio of approximately 10:1. Bolus injections of synthetic [Thr6]bradykinin into the jugular vein of the anesthetized alligator resulted in a dose-dependent decrease in mean arterial blood pressure. The minimum dose of kinin producing a significant fall in pressure was 0.07 micrograms/kg body wt and the maximum response (25 +/- 6% fall; mean +/- SD, n = 8) was produced by a dose of 0.56 micrograms/kg body wt. The dose producing a half-maximum response was 0.19 +/- 0.08 micrograms/kg. The data indicate that alligator plasma contains all the components of the kallikrein kinin system found in mammals and suggest that the system may be of physiological importance in the regulation of cardiovascular function in these reptiles. PMID- 1510180 TI - Renal afferent input to the ventrolateral medulla of the cat. AB - Experiments were performed to determine if information from the kidneys projects to the rostral ventrolateral medulla. Extracellular action potentials were recorded from 148 cells within the rostral ventrolateral medulla of alpha chloralose-anesthetized cats. Cells within the rostral ventrolateral medulla were tested for responses to electrical stimulation of both left and right renal nerves. Electrical stimulation of renal nerves excited 144 cells (97.3%) and inhibited 4. The majority of cells received either bilateral or contralateral renal nerve input. Cells with bilateral renal nerve input responded to contralateral renal nerve stimulation with a significantly greater number of impulses compared with ipsilateral renal nerve stimulation (P less than 0.05). All cells but one responding to renal nerve stimulation had convergent somatic input. Comparisons between thresholds for cell responses and activation thresholds for the A and C volleys of the compound action potential recorded in the least splanchnic nerve revealed that 44 cells required activation of A delta fibers, and 12 cells required activation of both A delta- and C-fibers. A conditioning stimulus applied to renal nerves on one side significantly decreased the response elicited by a test stimulus applied to the renal nerves on the opposite side for at least 300 ms (P less than 0.05). The demonstration that an afferent connection exists between the kidneys and the ventrolateral medulla suggests that the rostral ventrolateral medulla may play a role in mediating supraspinal reflexes of renal origin. PMID- 1510181 TI - Endotoxin-induced fever is modulated by endogenous glucocorticoids in rats. AB - This study was designed to determine if the febrile response, similar to the inflammatory response, can be modulated by endogenous glucocorticoids. A single intraperitoneal injection of lipopolysaccharide (LPS, 200 micrograms/kg) induced a significant increase in rectal temperature of unrestrained rats maintained within the thermoneutral zone. The febrile response was fully abolished following treatment with a glucocorticoid, dexamethasone (DEX), but was not affected by a mineralocorticoid, deoxycorticosterone acetate (DOCA). Adrenalectomized (ADX) rats were markedly more sensitive to the lethal effects of LPS (200 micrograms/kg), such that all the animals died during the course of the experiment. In addition, ADX rats showed an enhanced febrile response to LPS (10 micrograms/kg ip) in comparison with sham-operated or adrenal-demedullated rats. This enhanced response was reduced by chronic or acute treatment with DEX, but not DOCA. LPS (10 micrograms/kg) also induced a marked rise in plasma corticosterone levels in control rats. In contrast, ADX rats displayed very low plasma corticosterone levels, which were not changed by LPS. In conclusion, the present results reveal that endogenous glucocorticoids are important modulators of LPS-induced fever. PMID- 1510182 TI - High-intensity light for circadian adaptation to a 12-h shift of the sleep schedule. AB - Male subjects had their sleep schedules shifted 12 h to accommodate eight or more consecutive simulated night shifts. They were exposed to artificial light (approximately 5,000 lux, 3- to 6-h durations) each night, slept at home in very dark bedrooms during the day, and wore dark welders goggles whenever they went outside during daylight. Body temperature was continuously measured, and daily questionnaires provided estimates of sleep time and mood. The circadian temperature rhythm phase shifted, usually approximately 2 h/day, in 21 of 24 subjects. The temperature rhythms of the other three subjects appeared to remain entrained to the 24-h zeitgebers. In the subjects whose temperature rhythms shifted, the direction of shift (advance or delay) depended on the timing of light exposure relative to the baseline temperature phase, consistent with a phase-response curve. Sleep was disturbed, and fatigue was increased during the first few days after the shift of the sleep-wake schedule. PMID- 1510183 TI - Splanchnic nerve response to A5 area stimulation in rats. AB - Microinjection of the excitatory amino acid N-methyl-D-aspartate (NMDA, 0.5 nmol) into ventrolateral pons (the A5 area) of halothane-anesthetized, paralyzed rats increased splanchnic (sSND) and renal sympathetic nerve discharges (approximately 45%) and usually decreased lumbar SND. These effects were accompanied by 1) regionally specific changes in vascular resistances, 2) an increase in the gain of the sympathetic baroreflex, and 3) modest reductions in blood pressure and heart rate. sSND activation was greatest when NMDA injections were made in the vicinity of A5 noradrenergic (NE) cells. Injection of 6-hydroxydopamine (6-OH-DA) into A5 area (after 15 days) destroyed 83% of NE neurons and reduced NMDA activation of sSND by 76%. Stimulation of sSND by NMDA in A5 area was reduced 1) 1-2 h after bilateral intraspinal injection of 6-OHDA, but not vehicle or 5,7 dihydroxytryptamine, and 2) by administration of prazosin [alpha 1-NE receptor antagonist, 1 mg/kg iv or 10-20 micrograms intrathecal (it)], but not by idazoxan (alpha 2-NE receptor antagonist, 10-20 micrograms it) or propranolol (0.2 mg/kg iv). We conclude that A5 NE cells have a visceral vasomotor sympathoexcitatory function mediated in large part by their spinal projection. PMID- 1510184 TI - Cholecystokinin (CCK-8) affects gastric pressure and ratings of hunger and fullness in women. AB - Cholecystokinin (CCK) may affect food intake by augmenting neural activity from the distended stomach, thereby amplifying satiety signals. To test the hypothesis that subjects would report more fullness and less hunger with gastric distension when CCK-8 (112 ng/min) was infused than when saline was infused, a gastric balloon was inflated in the stomachs of four women. When the balloon was inflated to 500 ml, there was no difference in gastric pressure between the CCK-8 and saline conditions. Nonetheless, ratings of fullness were higher with CCK-8 administration. When the balloon was inflated to the maximum volume tolerated, the pressure rise was significantly smaller with CCK-8 infusion. In addition, fullness ratings rose and hunger ratings declined more steeply in relation to gastric pressure when CCK-8 was infused. In all conditions, gastric contractions were practically abolished with CCK-8 infusion. CCK-8 relaxed the stomach and concurrently sensitized the subjects to gastric pressure. PMID- 1510185 TI - Familial thrombocytopenia with micromegakaryocytes: what is the defect in thrombopoiesis? PMID- 1510186 TI - Thyroid function during L-asparaginase therapy in children with acute lymphoblastic leukemia: difference between induction and late intensification. AB - Parameters of thyroid function were measured in nine children during induction therapy for acute lymphoblastic leukemia (ALL). Seven patients were reevaluated during the late intensification phase. Vincristine, anthracycline drugs (daunorubicin and adriamycin), corticosteroids, and L-asparaginase were used in the two phases of therapy. During induction, L-asparaginase (5,000 U/m2) was given daily on days 1-21. During late intensification, the drug was given on days 1, 4, 8, and 11 (10,000 U/m2). During induction, total T4 significantly decreased from 10.1 +/- 2.3 to 4.0 +/- 1.0 micrograms/dl, FT4 decreased from 1.4 +/- 0.3 to 0.7 +/- 0.2 ng/dl, total T3 decreased from 134 +/- 32 to 57 +/- 21 ng/dl, and thyroxine binding globulin (TBG) decreased from 2.1 +/- 0.6 to 0.8 +/- 0.3 mg/dl. During late intensification therapy, significant decreases in T3 (from 180 +/- 26 to 93 +/- 40 ng/dl) and TBG (from 1.9 +/- 0.5 to 1.1 +/- 0.5 mg/dl) were observed, but there were no significant changes in T4 and FT4. We conclude that during induction, the impairment of thyroid function is attributable to L asparaginase, whereas during late intensification, low T3 and low TBG is due to glucocorticoid administration. PMID- 1510187 TI - Limb deformity and metaphyseal abnormalities in thalassaemia major. AB - Regular bone survey radiographs have allowed identification of limb deformity and metaphyseal changes in several patients with thalassaemia major treated at the Adelaide Children's Hospital. Following the progression of limb deformity in five of these patients who were receiving human growth hormone therapy, the records of 25 thalassaemia patients were reviewed. Six patients had evidence of limb deformity, four of whom also had metaphyseal changes. Three additional patients had metaphyseal changes alone. Patients with either type of skeletal change shared similar characteristics, including younger age, earlier commencement of desferrioxamine therapy, better compliance and, in general, lower levels of ferritin. Females predominated in both groups. The frequency of sensorineural hearing loss was similar in affected and nonaffected groups and biochemical parameters, especially plasma calcium, phosphate, alkaline phosphatase, and zinc, which were normal in all patients. The cause of these skeletal changes is not clear; however, several potential factors need to be considered. Among these are focal marrow expansion in the metaphyseal region due to incomplete suppression of erythropoiesis and possible effects of desferrioxamine, including direct interference with bone growth, altered response of bone to inflammation or infection, and altered bone metabolism related to chelation of trace metals. While we can only speculate on aetiological factors, it is clear that human growth hormone therapy has resulted in exaggeration of deformity due to an increased rate of bone growth or decreased rate of mineralization of physeal cartilage. We believe that bone survey radiographs are useful in early identification of skeletal changes.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1510188 TI - Continued remission in children with neuroblastoma despite elevations of urinary catecholamine metabolites. AB - Our experience at the Children's Hospital of Pittsburgh with a patient with neuroblastoma suggested that renewed elevations of urinary catecholamine metabolites may not necessarily be an indication of progressive disease. To test this possibility, we reviewed the courses of children with neuroblastoma who achieved a clinical status of "no evidence of disease" (NED), and in whom homovanillic acid (HVA) and/or vanillylmandelic acid (VMA) levels were subsequently noted to exceed normal limits initially in the presence of normal restaging studies. Five patients were identified. Of these, one had stage I, one had stage II, two had stage III, and one had stage IV disease at diagnosis. Elevations of their HVA and/or VMA levels following achievement of NED status ranged from 1 1/2 to 4 times maximal normal levels for age, and abnormalities persisted for 17 to 47 months. Only one patient relapsed, while the other four remain disease-free 8-12 years following diagnosis. These results confirm that in patients with neuroblastoma, mild elevations of HVA and/or VMA may be compatible with continuous remission. PMID- 1510189 TI - Prognostic factors in metastatic neuroblastoma. A multivariate analysis of 182 cases. AB - The purpose of our study was to investigate the interrelationship of known and possible new risk factors in patients with metastatic neuroblastoma and to define groups at risk. The possible influence of 37 variables on event-free survival (EFS) was analyzed univariately in 308 consecutive patients using the Kaplan Meier estimate. Fifteen factors were identified (p less than 0.05, logrank greater than 3.84) of whom eight showed a nonrandom correlation to several others (chi 2-test, p less than 0.05). Seven noncorrelated factors [lactate dehydrogenase (LDH) level, resectability of the primary tumor, histologic grade, leukopenia, presence of symptoms, general condition, and age at diagnosis] were included in the multivariate analysis of 182 patients according to the Cox model. The variables LDH (p = 0.0007), resectability (p = 0.0063), histologic grade (p = 0.0055), and leukopenia (p = 0.0470) were identified multivariately as prognostic factors for EFS. These results permitted the classification of patients into three prognostic groups. The 6 year event-free survival for group IV-A (LDH normal) was 0.37 +/- 0.12, for group IV-B (LDH abnormal, additional risk factors favorable) 0.18 +/- 0.10, and for group IV-C (LDH abnormal, 1-3 additional risk factors unfavorable) was 0.08 +/- 0.03. We conclude that the proposed clinicopathological classification may prove to be a reliable and easily applicable tool for estimating the outcome of metastatic neuroblastoma in children. PMID- 1510190 TI - Continuous epidural anesthesia for postoperative analgesia in the pediatric oncology patient. AB - When compared with conventional techniques, epidural anesthesia not only provides improved analgesia, but also has several beneficial effects on the postoperative respiratory, cardiovascular, and metabolic status of the patient. Although the efficacy of this technique in children has been demonstrated, extensive experience in the pediatric oncology patient has not been previously reported. We retrospectively reviewed our 2-year experience with epidural analgesia and discuss the techniques involved in implementing this service for the pediatric oncology patient. An epidural catheter was successfully placed in 58 of 60 patients (97%) who ranged in age from 4 months to 19 years and in weight from 4.1 to 68 kg. Postoperative analgesia was provided by a continuous infusion of a bupivacaine/fentanyl mixture, supplemented with intermittent epidural fentanyl by bolus dose as needed. No complications related to epidural catheters were noted. Our review supports the efficacy of this technique for providing postoperative analgesia after various major surgical procedures in the pediatric oncology patient. PMID- 1510191 TI - Oxygen therapy in sickle cell disease. AB - The effect of oxygen therapy on the number of irreversibly (ISC) and reversibly (RSC) sickled cells was studied in patients with sickle cell anemia. Inhalation of 50% oxygen in patients who were not in crisis produced a significant fall in RSCs and a lesser fall in ISCs. Twenty-five subjects in sickle cell crisis were chosen at random to receive either oxygen (15 patients) or air (10 patients). Those who received oxygen showed a significant reduction in RSCs, but not in ISCs. No significant change in RSCs or ISCs occurred in the group who received air. Despite the reduction in RSCs in the oxygen-treated group, there was no significant difference between the air and oxygen groups in the duration of severe pain, opioid administration, and hospitalization. It was also observed that crisis was associated with arterial desaturation and a reduction in the number of RSCs. We conclude that, although RSCs may be involved in the pathophysiology of sickle cell crisis, reduction in RSCs by oxygen therapy in these studies did not result in any reduction in the duration of crisis. PMID- 1510193 TI - HIV infection of multiply-transfused pediatric oncology patients in a low prevalence area. AB - We attempted to determine the occurrence of transfusion-acquired HIV-1 infection in multiply-transfused pediatric oncology patients receiving blood products prior to donor HIV antibody screening in March 1985. We identified 85 multiply transfused pediatric oncology patients (initially HIV-1 antibody negative) who had received 4,346 transfusions (968 red blood cells, 3,192 platelets, 137 fresh frozen plasma, and 49 leukocytes). Only one (1.2%) of these multiply-transfused pediatric oncology patients seroconverted following transfusion. Transfusion acquired HIV-1 infection in our multiply-transfused pediatric oncology patients was infrequent despite marked exposure to blood products (average 51.2 donor exposures per multiply transfused pediatric oncology patients) and occurred at a frequency consistent with the prevalence of HIV-1 infection in our donor population (Central Ohio--2 of 10,000 donors were HIV-1 antibody positive). While our findings may not be unexpected, they offer documentation of a lower risk for transfusion-acquired HIV infection in our blood recipients than in some previous studies conducted in areas where donor HIV antibody prevalence is higher. We also document that the efforts associated with performing "Lookback" evaluations (contacting recipients of blood products from donors subsequently identified as HIV antibody positive) are valuable since our only HIV-1-infected, multiply transfused pediatric oncology patient was identified in this manner. PMID- 1510192 TI - Survival of children with chronic myeloid leukemia. AB - We analyzed survival in 203 children with Philadelphia-chromosome-positive chronic myeloid leukemia (CML). Median survival was 4.1 years; average annual risk of death was 20%. These survival data are similar to those reported in adults. Because there is no possibility of long-term disease-free survival in children with CML with conventional therapies, the findings of this study suggest that bone marrow transplantation should be considered in these patients. PMID- 1510194 TI - Growth retardation in childhood leukemia and lymphoma. Special reference to patients with CNS relapse. AB - We studied the growth of 89 patients who were long-term survivors of childhood leukemia and lymphoma. Eight patients with CNS relapse had a greater decrease in height standard deviation score (SDS) after the relapse than 81 patients without CNS relapse (p less than 0.0001). Two patients who received cranial irradiation when they were younger than 2 years of age demonstrated a marked decrease in height SDS more than 3.0 SD. Five patients appeared to have a decline in height SDS before their CNS relapse. There were no apparent changes in the weight of patients with or without CNS relapse. In endocrine studies, all eight patients with CNS relapse failed to show the normal growth hormone (GH) response to arginine, GH-releasing factor, and glucagon-propranolol tests, while spontaneous GH secretion during sleep was normal. Magnetic resonance imaging (MRI) revealed small pituitary glands in seven patients with CNS relapse. These findings suggest that in leukemia and lymphoma patients with CNS relapse, GH secretion is impaired at the hypothalamic level, resulting in a secondary atrophy of the pituitary gland. The MRI together with selected endocrinologic tests may help to clarify the mechanism of growth impairment in such patients. A decline in height SDS in each patient may be a useful marker for predicting a CNS relapse in a child with leukemia or lymphoma. PMID- 1510195 TI - Megakaryocytes and megakaryocyte progenitors in human cord blood. AB - Thrombocytopenia contributes significantly to morbidity in the sick term or preterm infant. However, few data exist on newborn's megakaryocytes and megakaryocyte progenitor cells (CFU-MK). We therefore studied CFU-MK in term and preterm infant cord blood and compared the results with data on CFU-MK from adult bone marrow and adult peripheral blood in a plasma clot culture with postirradiated aplastic canine serum (PIACS) as a source of megakaryocyte colony stimulating activity. The number of CFU-MK and the number of cells per CFU-MK were counted with an immunofluorescent method at day 12. The effect of T lymphocyte depletion on cord blood cultures for CFU-MK was studied with PIACS and a partially purified product of PIACS. We also studied individual megakaryocytes from newborns. The number and sizes of circulating megakaryocytes, isolated from adult peripheral blood and term venous cord blood by elutriation, were compared. Term and preterm cord blood contained more CFU-MK than adult peripheral blood. The numbers of CFU-MK in preterm cord blood were comparable to those in adult bone marrow. When the number of cells per colony were compared, cord blood contained significantly more cells than adult marrow CFU-MK. The depletion of T lymphocytes did not significantly change the growth of CFU-MK compared to nondepleted cultures. A substantial number of circulating megakaryocytes were obtained from venous cord blood, though they were significantly smaller than adult peripheral blood megakaryocytes. Since cord blood is easily obtained and contains large numbers of megakaryocytes and CFU-MK, it may provide a convenient model for studying the regulation of fetal megakaryocytopoiesis. PMID- 1510196 TI - New observations in a child with angiofollicular lymph node hyperplasia (Castleman's disease) originated from the mesenteric root. AB - Localized plasma cell type Castleman's disease (CD) is an unusual pathologic entity. It is frequently associated with clinical and laboratory characteristics and rarely occurs in children. Total surgical excision results in cure in all aspects. To make early diagnosis of mesenteric CD is not easy, especially for children. An 11-year-old Taiwanese boy was recently evaluated for anemia and delayed growth. His clinical findings included a syndrome of severe hypochromic microcytic anemia, neutropenia, thrombocytosis, hypoferremia, hypergammaglobulinemia, and growth failure. Radiological examinations (abdominal ultrasound, small intestinal series, and computerized tomography) identified hepatosplenomegaly, nephromegaly, and huge masses in the middle abdomen with precaval, celiac, and paraaortic lymph nodal enlargement. However, detailed physical examination failed to detect a mass. At laparotomy a double-fist-sized confluent mass was found arising from the mesenteric root. Most masses were discrete and were excised individually. The pathologic diagnosis was plasma-cell type angiofollicular lymph node hyperplasia (Castleman's disease). Seven weeks after surgery, he had an episode of acute hepatitis B. Postoperatively, he exhibited a dramatic growth spurt; the hemoglobin, red blood cell indices, serum iron, and immunoglobulins returned to normal in 2 months. Neutropenia, which has not been previously related to mesenteric CD, was an unexpected finding in our case; however, it resolved spontaneously 3 months after the surgery, suggesting its causal relationship with the tumor. PMID- 1510197 TI - Synovial sarcoma associated with osteofibrous dysplasia. A case report and review of the literature. AB - We report on a 14-year-old boy who demonstrated an unusual association between osteofibrous dysplasia and synovial sarcoma. This case suggests that a patient who presents with osteofibrous dysplasia of the tibia can eventually develop a malignant musculoskeletal tumor in the same anatomical location (same limb). This experience suggests that a patient who presents with osteofibrous dysplasia should be followed up for the possibility of a coexisting synovial sarcoma in the same leg. PMID- 1510198 TI - Multiple subcutaneous leiomyosarcomas in an adolescent with AIDS. AB - The case of 17-year-old boy with thalassemia major who contracted the human immunodeficiency virus (HIV) through multiple transfusions is described. Eight years after the onset of generalized lymphadenopathy, and 5 years after the documentation of HIV infection on serologic grounds, he developed the first of multiple, painful, subcutaneous nodules, which proved to be leiomyosarcomas of vascular origin. The histopathology and possible pathogenesis of these unusual tumors are discussed. PMID- 1510199 TI - Disseminated Langerhans cell histiocytosis in identical twins unresponsive to recombinant human alpha-interferon and total body irradiation. AB - Monozygotic twin boys presented at 1 year of age with seborrheic skin rash, otorrhea, and hepatosplenomegaly. Skin biopsy confirmed Langerhans cell histiocytosis. Treatment with conventional antineoplastic drugs and with calf thymus extract was ineffective. The disease remained refractory to recombinant human alpha-interferon and to low-dose total body irradiation, and the children died between 3 and 3 1/2 years of age. PMID- 1510200 TI - Acute aseptic meningitis associated with administration of intravenous immune globulin. PMID- 1510201 TI - N-acetylcysteine protects skin lesion induced by local extravasation of doxorubicin in a rat model. PMID- 1510202 TI - Sexually speaking ... when the recipe for baby making doesn't work. The psychological aspects of infertility: Part I. In search of the magical recipe. PMID- 1510203 TI - Alaska nursing home takes national role in addressing urinary incontinence. AB - Urinary incontinence affects over half of all residents in the nation's 25,000 nursing homes. While incontinence assessment, treatment and management techniques have been validated under "laboratory" conditions, the practicality of maintaining the systems pose difficulties for most nursing homes. An evaluation of a new automated system for managing urinary incontinence indicates that a nursing home in Anchorage, Alaska, has successfully implemented and maintained the new system for over ten (10) months. Researchers found that The Mary Conrad Center quickly reduced wetness rates in the target group from 25 percent prior to implementation of the program, to about eight percent and have been able to reduce wetness rates to even lower levels in subsequent months. The evaluation provides critical evidence that nursing homes can implement and maintain the comprehensive system. If further testing in other facilities result in similar findings, the system stands to impact the quality of care for over one million nursing home residents affected by urinary incontinence. PMID- 1510204 TI - Efficient appointment scheduling reduces delays and patient anger. PMID- 1510205 TI - History of medicine in Alaska. PMID- 1510206 TI - Aleut healers and their heritage (1824-1834). PMID- 1510207 TI - Body composition testing of athletes in the field using bioelectric impedance analysis. AB - Bioelectric impedance analysis was performed as part of the field testing of seventeen athletes competing in the 1990 Iditarod Sled Dog Race. The purpose was to measure initial body composition and the changes that occurred during this extended performance period under Arctic conditions. Four women and thirteen men aged 26-53 years were tested to measure changes in their lean body weight, total body water, total body fat and percent body water. Study results record average body fat losses of 2.14 kg in the male and 1.02 kg in the female racers. Total body water and lean body mass remained stable, while an increase in body water percentage (men: 4.31%, women: 2.78%) was recorded. Though questions remain, bioelectric impedance analysis demonstrates potential for use in future field research projects. PMID- 1510208 TI - Analysis of the rural medivac system in the Copper River area. AB - A pattern of increasing use of aeromedical transport has been observed in the Copper River area of Central Alaska. A retrospective chart review was made to determine the reasons for these medivacs, and the outcome of the patients who were transferred by air ambulance from Cross Road Medical Center in Glennallen, Alaska. In this series there were no unexpected adverse outcomes. Additional or more accurate diagnoses were made on nearly one fourth of the patients. Ninety two percent of those medivaced were hospitalized with 21 percent needing emergency surgery and 16 percent needing an ICU bed. All categories of patients showed benefit from transport to a higher level facility. There were no complications resulting from the transport. PMID- 1510209 TI - Neonatal circumcision in Anchorage 1985-1990. PMID- 1510210 TI - For the record ... Don Young: on CHIPRA. PMID- 1510211 TI - DNA flow cytometry of primary tumors and their skin metastases. Correlation of DNA histograms. AB - The purpose of this study was to determine whether quantification of DNA content would demonstrate conserved patterns in primary tumors and their metastases and to learn whether this technique would be useful in determining if a tumor was metastatic from a previous primary tumor or represented a new neoplasm. The study comprised of all cases nonmelanoma metastatic skin lesions in which the primary tumor was also resected at this hospital between the years 1984 and 1990 (22 cases). Both the primary and metastatic lesions were examined by the deparaffinized flow cytometric technique for DNA content. DNA-aneuploid tumors were considered to correlate if the DNA indices (ratio of aneuploid to diploid peak channels) were within 10%. Thirty-four tumors were DNA-aneuploid; eight tumors were DNA-diploid. We found agreement in 20 of 22 cases (agree--aneuploid: 16 cases; agree--diploid: four cases). In six of our cases the histograms of the primary and the metastatic lesions did not correlate when only one block was examined; however, when three blocks from each site were studied, we found concordance of DNA indices in four cases. There was disagreement in two of 22 cases (disagree--different DNA indices: two cases). In both of these cases, only one block of the primary tumor was available for examination, and the histograms were of marginal quality. This study demonstrates that the histogram pattern (aneuploid versus diploid) of DNA content is highly conserved between primary and metastatic tumors. There was 91% agreement between DNA indices of primary tumors and their metastases (20 of 22 cases) using a 10% correlation criterion.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1510213 TI - A dose of salts. PMID- 1510212 TI - Dysplastic nevus syndrome among Japanese. A case study and review of the Japanese literature. AB - Three Japanese families with dysplastic nevus syndrome (DNS) are reported. Each family had at least two members with multiple dysplastic nevi (DN). Family members with DN or multiple moles had paler skin than average Japanese, usually sunburned, and tanned less than average, whereas members with darker skin almost never had DN. Each of two families had one cutaneous malignant melanoma (CMM) patient associated with multiple DN. Both CMMs were on the leg. In Japanese DNS, skin color and sun sensitivity seem to be closely related to DN. The locations of CMMs associated with DNS were unique: No CMMs were found on acral areas where they most frequently occur in Japanese. PMID- 1510214 TI - Congenital rhabdomyomatous mesenchymal hamartoma. PMID- 1510216 TI - Granulomatous mycosis fungoides. Clinicopathologic study of two cases. AB - Granulomatous mycosis fungoides is a rare form of mycosis fungoides with controversial histogenesis. Early reports seemed to indicate a favorable prognosis for these patients. We report two cases of granulomatous mycosis fungoides, both of which had other unusual clinical features. The cases were studied with routine light microscopy, immunohistochemistry, electron microscopy, and gene probe studies. Despite some clinical and histopathologic similarities, the results of the immunohistochemical and molecular biologic studies were diverse. These results suggest that granulomatous mycosis fungoides does not define a single subset of cases, immunophenotypically or biologically. PMID- 1510215 TI - Mutant p53 protein is expressed in Bowen's disease. AB - A total of 26 specimens of histologically determined, cutaneous Bowen's disease from 23 patients were investigated for the incidence of mutant p53 protein expression by an indirect immunoperoxidase technique using the monoclonal antiserum CM1 on paraffin-embedded formalin-fixed tissue sections. Its potential role as a label of cutaneous malignancy was also evaluated: 15 specimens (57.7%) showed nuclear positivity of dysplastic keratinocytes, whereas 11 specimens (42.3%) were immunonegative. Cytoplasmic labeling was never a feature. In general, labeling was predominantly diffuse in distribution although in a significant proportion it was focal. One of two concurrent basal cell carcinomas arising adjacent to plaques of Bowen's disease was immunopositive. Focal immunopositivity of "cytologically normal" adjacent epithelium was seen in six specimens (23%). The study confirms the presence of mutant p53 protein in the majority of nongenital Bowen's disease. Its identification within nuclei of the adjacent "normal" epidermis may represent a potential marker of early (visible) neoplastic transformation. PMID- 1510217 TI - Palisading granulomas caused by infectious diseases. AB - We recently encountered a palisading granuloma in which an infectious cause was not considered until special stains revealed hyphae and tissue culture revealed organisms of phaeohyphomycosis. A review of more than 2,500 cases of various granulomas revealed 11 cases of palisading-type granuloma caused by infection, including phaeohyphomycosis, nontuberculous mycobacteriosis, papulonecrotic tuberculid, tuberculoid syphiloderm, cat-scratch disease, sporotrichosis, cryptococcosis, and coccidioidomycosis. Infectious disease should be considered in the differential diagnosis of palisading granuloma. Special stains for bacteria, fungi, and acid-fast bacilli should be performed in biopsy specimens that have a palisading granuloma pattern with central necrosis, especially in immunosuppressed patients. PMID- 1510218 TI - Clinicopathological correlation in chronic urticaria. AB - Except for urticarial vasculitis, histopathological studies on the different types of urticaria are scant in the medical literature. With the purpose of evaluating the histopathological changes that occur in chronic urticarial eruptions, and to correlate the histopathological findings with the clinical presentation of the patients, skin biopsy studies were done in 36 patients with chronic urticaria. Three well-defined histopathological patterns were found: namely neutrophilic, lymphocytic, and mixed type. No cases of vasculitis were found. No specific association to the clinical presentation of the patient was found. PMID- 1510219 TI - Histopathologic differences in the photoaging process in facial versus arm skin. AB - We used clinical criteria to study skin biopsy specimens with mild to moderate photoaging taken from the face and dorsal forearms of 74 Caucasian volunteers between the ages of 30 and 50. Facial skin had a greater number of granular cell layers, a higher degree of keratinocytic atypia, and more often showed a compact stratum corneum than arm skin. Furthermore, the dermis of facial skin had a more extensive perivascular and perifollicular lymphocytic infiltrate, more perifollicular fibrosis, a greater number of mast cells and melanophages, and thinner vascular walls than forearm skin. This study demonstrated that the photoaging process is different for face and arm skin. Appreciation of these differences should permit more refined studies of photoaging and the development of more efficient therapies. PMID- 1510220 TI - Relationship of tumor cell motility and morphologic patterns. Part 1. Melanocytic skin tumors. AB - In the diagnosis of melanocytic skin tumors, the assessment of the overall architectural pattern (silhouette) is often essential. We have previously shown by a computer simulation model that tumor patterns are likely to depend on the relative degrees of proliferation and motility of the tumor cells. In this study, we examined the morphological pattern of 12 cases each of nevocellular nevi, primary melanoma, and metastatic melanoma by image analysis. The patterns of the individual melanocytic skin tumors were compared statistically with patterns generated by computer simulation, which facilitates estimates of biological properties of the tumor cells. Additionally, mitotic counts were made to measure tumor cell proliferation. A comparison of the three diagnostic groups revealed that the cells of nevocellular nevi show a low degree of motility, which, however, still exceeds the very low degree of proliferation. Thus, an "invasive" pattern with numerous small nests and single cells at the base of the lesion is common. In primary malignant melanoma, tumor cell motility and tumor cell proliferation are significantly increased in various proportions, thus leading to varying morphological patterns. In metastatic melanoma, a strikingly elevated degree of proliferation exceeds the only slightly elevated degree of motility and leads to sharply demarcated, "expansive" lesions. To check the validity of the technical procedure, estimates of proliferation based on pattern analysis alone were compared with the results obtained by mitotic counts. There was a significant correlation, indicating that the assumptions of the computer model and the image analysis procedure are in fact applicable to real-life melanocytic skin tumors.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1510221 TI - Critique of definitions about melanocytic proliferations formulated by an N.I.H. panel. PMID- 1510222 TI - Complex adnexal tumor of the primary epithelial germ with distinct patterns of superficial epithelioma with sebaceous differentiation, immature trichoepithelioma, and apocrine adenocarcinoma. AB - A 60-year-old man came for treatment of a sharply outlined erythematous plaque on the gluteal area (45 x 20 mm) of 20 years' duration. Eccentrically located on the plaque was a nodule, 20 mm in diameter. Histological study of the plaque showed a superficial platelike tumor with basaloid bland cytology and sebaceous gland differentiation. Histologic study of the nodule found an undifferentiated adenocarcinoma whose ductlike glandular structures opened to the skin surface and infiltrated the whole depth of the dermis. Study of other areas of the lesion detected two more neoplasms. A nodule of squamous cell carcinoma was found within the superficial band of the benign sebaceous tumor. The fourth neoplastic pattern consisted of epithelial islands composed of basaloid cells within a fibroblastic stroma. There was prominent palisading of epithelial cell nuclei at the periphery of the islands, which usually were surrounded by a sheath of mesenchymal cells. In this complex adnexal tumor of the primary epithelial germ, sebaceous and follicular differentiation both simulate neoplastic patterns recently described as separate entities: superficial epithelioma with sebaceous differentiation and immature trichoepithelioma. The undifferentiated adenocarcinoma may represent differentiation toward the third component of the germ, that is, the apocrine gland. PMID- 1510223 TI - Actinic granuloma of the conjunctiva. AB - Few cases of actinic granuloma of the conjunctiva have been reported. A 39-year old woman developed a pinguecula. A biopsy study revealed actinic granuloma histopathologically. This case is an example of the interface between dermatology and other fields, and helps to confirm the existence of actinic granuloma of the skin as a distinct entity. PMID- 1510224 TI - Malignant Triton tumor. A case with protean histopathological patterns. AB - A case of malignant Triton tumor occurring in the leg of a 48-year-old woman with neurofibromatosis (von Recklinghausen's disease) is presented. The neoplasm was composed mainly of spindle-shaped cells forming interlacing fascicles with areas of massive necrosis. The important feature in this neoplasm was the presence of rhabdomyoblastic cells admixed with other cellular components. In addition, variable histologic features including solid, myxomatous, hemangiomatous, hemangiopericytomatous, epithelioid, and lymphomatous areas were identified. This variety has been recognized in malignant schwannomas, but not in malignant Triton tumors. There were discrete foci with each predominant histologic feature shown in a map of the neoplasm in which the distribution of those components is demonstrated based on the histology and immunohistochemistry. Satisfactory biopsy specimens are necessary for accurate diagnosis of malignant Triton tumor. PMID- 1510225 TI - Carcinoid tumor with skin metastasis. AB - An 80-year-old male patient presented with a 4-month history of nine extremely painful cutaneous nodules located on his forehead, neck, thorax, arms, and thighs. Biopsies of two nodules were performed. Routine histology, immunohistochemistry for chromogranin, as well as electron microscopy demonstrated that the nodules corresponded to cutaneous metastases of a carcinoid tumor, probably originated in the gastric antrum. The present description is, to the best of our knowledge, the first one to correlate the spontaneous and pressure-induced pain in the nodules with perineural invasion and neural sectioning by tumoral cells. S-100 protein and electron microscopy demonstrated numerous Langerhans cells among the tumoral cells. PMID- 1510226 TI - A critical analysis of textbooks of dermatopathology in historical perspective. Part 1. PMID- 1510227 TI - Sex differences in skin pigmentation illustrated in art. AB - In different cultures of the world, many artists have made their female models lighter skinned than male models. There exists a biologic truth behind these observations. Several spectrophotometric studies have found that female skin reflectance is 2-3 percentage points above (that is, paler skin) that of males in diverse populations in Europe, Asia, Africa, and North and South America. The sex difference in skin pigmentation is, however, subtle and often difficult to appreciate. Probably artists have used pigmentation to emphasize sexual differences between men and women in the same way they use body size and musculature. PMID- 1510228 TI - Histochemical determinations of copper, zinc, and iron in pigmented nevi and melanoma. PMID- 1510229 TI - Hypo- and hyperpigmented areas in incontinentia pigmenti. Reply by Zillikens et al. PMID- 1510230 TI - Microorganisms and exacerbation of chronic obstructive pulmonary diseases: pathophysiological mechanisms. PMID- 1510231 TI - Detection of airborne reindeer epithelial antigen by enzyme-linked immunosorbent assay inhibition. AB - Hypersensitivity reactions to reindeer epithelial (RE) allergens have been recently demonstrated among reindeer herders. To determine the concentration of airborne RE antigens a method based on inhibition of the enzyme-linked immunosorbent assay (ELISA) was developed. Dust samples were collected in workshops where reindeer leather was processed and the workers had inhaled dry epithelial dust during their working shifts. Specific IgE to RE allergen could be detected in one of 5 workers. RE antigen concentrations varied from 0.01 microgram to 3.9 micrograms/m3 in the air of the workshop. All workers except one claimed work-associated respiratory symptoms. PMID- 1510232 TI - Allergic symptoms up to 4-6 years of age in children given cow milk neonatally. A prospective study. AB - In a previously published prospective study, we followed the development of allergic symptoms in term infants with a slightly reduced birthweight (-1 SD to 2 SD). These children received, according to local routine, early feeding with cow milk formula in order to diminish such neonatal problems as hypoglycemia and hyperbilirubinemia. Of 216 infants 207 were observed for allergic symptoms up to 18 months of age. One group (F) received cow milk formula during the first days of life before the mother's breastmilk production started and was then breastfed; the other (B) was not given any formula before normal breastfeeding started. Unexpectedly, we found fewer allergic symptoms, in particular allergic skin problems, in the group fed cow milk, the difference being concentrated to children with a family history of allergic symptoms. At 5 years of age 183 of the 207 children have been reinvestigated. Mild symptoms of allergy (suspected and obvious) were found in 22% (F) and 27% (B) respectively (NS). Moderate and severe symptoms of allergy (obvious) were found in 4.2% (F) and 4.5% (B). In the subgroup with a double family history of allergic symptoms, 28% (7/25, F) and 59% (10/17, B) had symptoms of allergy (p less than 0.05). This difference was even more pronounced when laboratory tests in favour of atopic diagnosis were included, 14% (F) and 53% (B) respectively (p less than 0.05). Thus at 5 years we still find a significantly lower frequency of allergic symptoms in the subgroup fed cow milk formula early with a family history of allergic symptoms.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1510233 TI - Comparison of the Phadebas RAST with the Pharmacia CAP system for insect venom. AB - Determination of specific IgE by RAST is a well-established method in the diagnosis of immediate allergic reactions. In this study, we have compared the RAST with the ImmunoCAP, a novel test system which is based on a new type of solid phase. A total of 123 sera from 111 insect venom-allergic patients (74% female) were investigated. All patients had their diagnosis confirmed on the basis of their history and skin tests with insect venom. The patients' age showed a mean +/- S of 44.2 +/- 14.6 years. The total serum IgE levels ranged from 4 1712 kU/l, with a median of 108 kU/l. The results of specific IgE, as determined by RAST and CAP, showed a significantly higher sensitivity, by almost one class, with the CAP compared with the RAST system. The quotient of specific IgE to total IgE, determined with the CAP system, could not be shown to be an expression of sensitization, compared with the severity of sting reactions (Muller classification (16)). A conversion factor for vespid venom RAST to CAP was calculated from the present data by subtracting the RAST from the CAP values. The mean delta value +/- SD was found to be 0.9 +/- 0.65, with a range from -0.8 to 2.7 and a median of 0.9. The data clearly show the differences between RAST and CAP-RAST classes, indicating that the CAP-system has a higher sensitivity and that patients with a low level sensitization are missed by the RAST method. PMID- 1510234 TI - Prospective estimation of IgG, IgG subclass and IgE antibodies to dietary proteins in infants with cow milk allergy. Levels of antibodies to whole milk protein, BLG and ovalbumin in relation to repeated milk challenge and clinical course of cow milk allergy. AB - Prospectively, serum levels of IgE, specific IgE antibodies (AB) to whole cow milk protein (CMP), bovine se-albumin, bovine immunoglobulin, bovine lactoferrin, bovine lactalbumin and beta-lactoglobulin (BLG), IgG and IgG subclass antibodies to ovalbumin (OA) and BLG, and IgG4 RAST to CMP (bovine whey) were measured in 39 infants with cow milk protein allergy (CMPA) at birth (cord blood), at time of diagnosis and before and after milk challenge at the age of 12 months. Immunological measurements were also undertaken in 33 control infants without CMPA at birth, at 6 months and at 18 months. At no time, were differences found between the levels of IgG and IgG subclass AB to OA and BLG in control versus infants with CMPA. In the 39 infants with CMPA no correlation was found between the levels of IgE, IgG and IgG subclass AB in cord blood and subsequent levels of these values, irrespective of the type of CMPA (IgE-mediated (CMA) or non-IgE mediated (CMI)), and irrespective of whether remission had occurred. In cord blood 25/33 (76%) of the infants with CMPA had specific IgE-AB to one or more of the bovine milk proteins indicating a prenatal intrauterine sensitization to cow milk protein. At 6 months the frequency of specific IgE-AB to bovine milk proteins was significantly (p less than 0.05) higher in infants with CMA versus CMI, and at 12 months total serum-IgE and the increase of these specific IGE-AB and RAST to CMP were significantly higher (p less than 0.05) in infants with persistent CMA. From 6 to 12 months withholding milk resulted in a significant fall in specific IgE-AB to CMP, and IgG, IgG1 and IgG4 anti-BLG followed by an increase after milk challenge. Decreasing levels of IgG anti-OA from birth to 6 months reflect passive maternal transfer of IgG through the placenta, and increasing levels of IgG anti-BLG, already from birth to 6 months, may represent an early exposure to CMP in all infants. Significantly higher levels (p less than 0.05) of IgG anti-OA AB, IgG1 and IgG4 anti-BLG AB were found in infants with persistent CMA, indicating a close relation between the synthesis of IgE and IgG and between IgE and IgG subclasses (IgG1 and IgG4) in symptomatic cow milk allergic individuals.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1510235 TI - Immunologically induced purulent anterior segment inflammation of the guinea pig eye. AB - A single conjunctival application of ovalbumin to inbred guinea pigs (IMM/S 209) immunized with the same antigen in Freund's complete adjuvant provoked an acute purulent inflammation of the anterior segment of the eyes with a duration of up to 1 week. Intense conjunctival injection and chemosis were followed by a purulent discharge. A corneal haze was observed regularly, and a considerable proportion of the animals developed a pronounced pannus and corneal ulcers. Tear fluid cytology revealed a rapid increase in cell concentration, from the normal level (less than 10(8)/l) to greater than 10(11)/l. Seventy to 95% of the cells were polymorphonuclear leukocytes. Histological examination revealed an acute inflammatory reaction which radiated from the conjunctival fornices to the entire anterior segments of the eyes. The process was characterized by an intense oedema, vasodilation and perivascular aggregations of polymorphonuclear leukocytes, and to a lesser extent eosinophilic granulocytes which characteristically infiltrated and penetrated the epithelial layers. Neovascularization could be observed early after challenge in the stroma of all parts of the outer eye. Ulcerations of the conjunctival and corneal epithelia were observed frequently. After a number of reiterations of the antigenic challenge, a marked infiltration with lymphocytes and basophils/mast cells was observed, and significant scarring of the conjunctival mucosa developed. In several animals, a slight, but significant co-reaction of the contra-lateral, non challenged eye was observed. PMID- 1510236 TI - Prevalence of atopic disorders among adolescents in Turku, Finland. AB - A study of the prevalence of atopic disorders among 15-16-year-old teenagers was carried out in a coastal urban town in south-western Finland. Altogether, 1712 children were found in that age group, all previously examined by a pediatrician. Each child who had present or previous allergic diseases was invited for a detailed study, a total of 434 (25%) pupils. Of these patients 416 (95.8%) participated in clinical examination and skin testing. The prevalence of atopic diseases was 21% in the studied group; atopic eczema was found in 9.7%, allergic rhinitis in 14% and asthma in 2.5%. Of subjects who had rhinitis, 38% also had atopic eczema, while rhinitis--as the only symptom--was found in 8.8%. Figures obtained from this survey suggest that the prevalence rates of atopic diseases are about the same as found 10 years ago in Finland and they correspond also with other recent reports. PMID- 1510237 TI - Immunotherapy in patients allergic to cat and dog dander. I. Clinical results. AB - Twenty-four asthmatics allergic to cat and/or dog dander were included in a study to examine the efficacy and safety of immunotherapy (IT) with partially purified, standardized extracts of cat or dog dander. In the first placebo controlled, double-blind part of the study, 10 patients were treated with extracts of both cat and dog, 12 with cat extracts and 2 with dog extracts. Fifteen patients received active IT and 9 placebo injections. Patients treated with both extracts received active extracts only, or placebo only. Bronchial allergen challenge after 5 months demonstrated a significant fall in sensitivity to cat (P = 0.04) in patients treated with cat extracts. No significant changes were found in sensitivity to dog after treatment with dog dander extract or in the placebo groups. During this period, bronchial sensitivity to histamine did not change significantly in any of the groups. To examine the effect of more prolonged IT, 19 patients allergic to cat (17) and/or dog (9) were treated for 12 months. Bronchial sensitivity to cat decreased further (P = 0.003), while no significant change was found in dog extract-treated patients. In cat extract-treated patients a significant decrease in bronchial histamine sensitivity developed (P = 0.02). Systemic side effects were few, but in some cases, local side effects were a dose limiting factor. This study demonstrated that IT with cat extract may benefit cat allergic asthmatics, whereas no influence of IT with dog extract was detected in dog-sensitive asthmatics. PMID- 1510238 TI - Flow cytometric analysis of intraepithelial lymphocytes in the human nasal mucosa. AB - Recently, much research has been carried out on phenotypes and the function of intraepithelial lymphocytes of the intestines. However, only few studies have been made of nasal intraepithelial lymphocytes (nIEL), and the results have been controversial. We examined the population of different subsets of the human nIEL by means of 2-color flow cytometry after culturing lymphocytes isolated from the inferior turbinates of hypertrophic rhinitis in incubation media with monoclonal antibody against CD3. As a result, CD8+ cells (suppressor/cytotoxic T cells) and double negative T cells (CD8- CD4- T cells) were the most predominant. The CD4+ cells (helper/inducer T cells) to CD8+ cells ratio was 0.6. Cytotoxic T cells predominated over suppressor T cells in CD8+ cells and helper T cells predominated over inducer T cells in CD4+ cells. Double positive T cells (CD8+CD4+ T cells) were nil and natural killer cells and CD8+ killer cells few. CD8+ cells and CD4+ cells were activated during cell culture. alpha beta receptor bearing T cells predominated over gamma delta receptor bearing T cells in CD8+ cells and CD4+ cells but gamma delta receptor bearing T cells predominated over alpha beta receptor bearing T cells in double negative T cells. To investigate the effect of cell culture on the population of each phenotype of nIEL we also examined peripheral blood lymphocytes by flow cytometry before and after culture, and found that activated T cells markedly increased and suppressor T cells, gamma delta bearing T cells and natural killer cells slightly decreased.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1510239 TI - Immediate adverse reactions to immunotherapy in allergy. AB - We report our experience of adverse reactions to immunotherapy (IT) in patients with insect venom allergy and inhalant respiratory allergy. Adverse reactions included large local reactions, generalized cutaneous reactions or systemic reactions. Among 87 patients treated for venom allergy, 43% had adverse reactions during the course of IT, averaging 2.5 reactions per patient and per course of IT. Nine had systemic reactions, of which 7 required adrenaline administration. Among 52 patients treated with inhalant allergen extracts, 40% had adverse reactions averaging 3 reactions per patient per course of treatment. Ten patients had systemic reactions but only 2 required adrenaline administration. There was no difference between the rate of adverse reactions in the venom and the inhalant treatment groups. IT has an inherent risk which has to be weighed against its benefits. PMID- 1510241 TI - Different effects of physical training on the morphology of motor nerve terminals in the rat extensor digitorum longus and soleus muscles. AB - The morphology of nerve terminals in the rat extensor digitorum longus and soleus muscles was studied with light microscopy in 13-week-old male animals after 6 weeks of treadmill running and compared with data from untrained controls. The terminals were stained with methylene blue. Physical training tended to increase the area and length of the nerve terminals in relation to the corresponding muscle fiber diameter, and to reduce the density of nerve terminal varicosities, but significant differences between the trained group and the control group were obtained only in the extensor digitorum longus muscle. The different degrees of effect on the nerve terminals in the two muscles may be due to different abilities to respond to the training, but may also be due to differences in work load caused by the training. The effect of training on extensor digitorum longus junctions may reflect some transformation from fast to slow morphological characteristics. PMID- 1510242 TI - Computer-assisted 3D-reconstruction and statistics of the limbic system. 1. Computer-assisted 3D-reconstruction of the hippocampal formation, the fornix, and the mamillary bodies. AB - The hippocampal formation of eight perfusion-fixed human brains was examined using new methods according to stereotactic and morphometric principles (macrovibratome and computer-aided 3D reconstruction). The reconstructions form part of a neuroanatomical reference system (NeuRef). This reference system allows for 3D visualisation of the brain and its components on a computer graphic workstation, as well as for the presentation of the union set based on a neuroanatomical structure taken from this sample of brains. This retrievable knowledge of neurofunctional systems is important for the preoperative planning of neurosurgeons and the adjustment of radiotherapy. PMID- 1510243 TI - Computer-assisted 3D-reconstruction and statistics of the limbic system. 2. Spatial statistics of the hippocampal formation, the fornix, and the mammillary bodies. AB - A statistical method is described to show the distribution of neuroanatomical structures within a Cartesian coordinate system from any given number of examinations. The algorithm is based on polygons derived from the outlines of neuroanatomical structures in parallel canthomeatal-orientated cutting planes. These polygons are transformed in virtual voxels, rotated into the bicommissural coordinate system, and projected onto the three main planes of this coordinate system. Areas with the same probability for the structures examined are given in these planes. As an example this method is applied to the hippocampal formation and the results attained are shown. PMID- 1510240 TI - The membranous skeleton: the role of cell condensations in vertebrate skeletogenesis. AB - Elements of the vertebrate skeleton are initiated as cell condensations, collectively termed the 'membranous skeleton' whether cartilages or bones by Gruneberg (1963). Condensations, which were identified as the basic cellular units in a recent model of morphological change in development and evolution (Atchley and Hall 1991) are reviewed in this paper. Condensations are initiated either by increased mitotic activity or by aggregation of cells towards a centre. Prechondrogenic (limb bud) and preosteogenic (scleral ossicle) condensations are discussed and contrasted. Both types of skeletogenic condensations arise following epithelial-mesenchymal interactions; condensations are identified as the first cellular product of such tissue interactions. Molecular characteristics of condensations are discussed, including peanut agglutinin lectin, which is used to visualize prechondrogenic condensations, and hyaluronan, hyaladherins, heparan sulphate proteoglycan, chondroitin sulphate proteoglycan, versican, tenascin, syndecan, N-CAM, alkaline phosphatase, retinoic acid and homeo-box-containing genes. The importance for the initiation of chondrogenesis or osteogenesis of upper and lower limits to condensation size and the numbers of cells in a condensation are discussed, as illustrated by in vitro studies and by mutant embryos, including Talpid3 in the chick and Brachypod, Congenital hydrocephalus and Phocomelia in the mouse. Evidence that genes specific to the skeletal type are selectively activated at condensation is discussed, as is a recent model involving TGF-beta and fibronectin in condensation formation. Condensations emerge as a pivotal stage in initiation of the vertebrate skeleton in embryonic development and in the modification of skeletal morphology during evolution. PMID- 1510244 TI - Morphological observations on the harderian gland of the North American opossum (Didelphis virginiana). AB - The Harderian gland of the North American opossum (Didelphis virginiana) is large and well developed, despite the absence of a nictitating membrane in the adult of this species. The elongate glands are surrounded by a delicate connective tissue capsule from which thin septae extend, subdividing the gland into numerous lobules. The secretory units of the opossum Harderian gland are drained by a well defined but not extensive intralobular and interlobular duct system. Most of the secretory end pieces consist of tubulo-alveolar units with widely dilated lumina filled with secretory product. Numerous intact lipid vesicles suspended within an amorphous material constitute the luminal contents. Cells lining the tubulo alveolar secretory end-pieces are usually columnar in shape, and characterized by numerous lipid-containing secretory vesicles and aggregations of poly-tubular complexes 40-60 nm in diameter. In addition, these cells contain numerous large irregularly shaped mitochondria, whose matrix is of considerable electron density. Intralobular and interlobular ducts are lined by electron-lucent epithelial cells that lack both the lipid-containing vesicles and the large mitochondria, although typical smaller mitochondria are found scattered within the cytoplasm. Both secretory end-pieces and ductal elements are invested by an abundance of myoepithelial cells. A second, smaller serous type of secretory unit may occur near the centre of some Harderian gland lobules. In these units secretory tubules and acini are compactly arranged surrounding a narrow lumen. Serous cells are pyramidal in shape and the cytoplasm is characterized by numerous electron-dense secretory granules and scattered profiles of rough endoplasmic reticulum.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1510245 TI - Regeneration in Salaria pavo (Blenniidae, Teleostei). Histogenesis of the regenerating pectoral fin suggests different mechanisms for morphogenesis and structural maintenance. AB - The pectoral fin of blennies is differentiated into a dorsal field and a ventral hook field. A histogenetic analysis of the regenerating pectoral fin was related to two questions. First, are histological specializations of the hook field responsible for the impairment of the regenerative capacity of pectoral fins of blennies? Second, can analysis of the temporal sequence of histogenetic events be used to make testable predictions about the tissue interactions required to re establish the adult pattern? Regeneration of pectoral fins was examined in Salaria pavo (Blenniidae, Teleostei). Approximately 80% of the length of the fin rays was amputated. Fin ray stumps were evaluated 7, 14, 24, 48 and 72 h after amputation, regenerates 4, 5, and 6 days after amputation and at length of about 30%, 50% and 60% regeneration of the original fin length. The regeneration process is subdivided into four stages: wound healing, blastema formation, fin ray formation and distal outgrowth and differentiation of hook characters. Analysis of the early events of regeneration, wound healing, blastema formation and distal outgrowth, yielded no profound differences from those of conventional fins in general. Impairment of regenerative capacity becomes manifested before histological differentiation of hook characters, and it is thus unlikely that their presence is the proximate cause of heteromorphic regeneration. The sequence in which the anatomical specializations characteristic of fin hooks (lepidotrichal cord, cuticle, fin web regression) appear was variable. Detailed analysis of older regenerates revealed a more regular pattern. In the first phase the characters appear to be largely independently organized, while they become locally correlated later. It is concluded that the anatomical differentiation passes through two stages, initiation of anatomical differentiation, and then mutual adjustment of character expression leading to spatially correlated expression of the lepidotrichal cord, the cuticle and the fin web regression. PMID- 1510246 TI - Silver impregnability of ischemia-sensitive neocortical neurons after 15 minutes of cardiac arrest in the dog. AB - The development of postischemic neuronal argyrophilia and the subsequent fate of argyrophilic neurons were studied in dogs after 15 min of complete cerebral ischemia and survival varying from 1 h to 7 days. Histopathological examination of the vulnerable neocortical region was performed using the Nauta degeneration method, and the time course of cellular changes was described. Clear-cut neuronal argyrophilia was found to precede cell body shrinkage and gradual disintegration corresponding to selective neuronal death. To clarify this initial stage of neuronal impregnability, the samples from the animals surviving 8 h postarrest were stained with toluidine blue or processed for electron microscopy, and the distribution of argyrophilic cells was confirmed to be identical with that of hyperchromatic or electron-dense cells. On the other hand, infrequently observed "tissue infarctions" exhibited no silver affinity in spite of apparent cellular damage. These findings indicate that enhanced impregnability is related to cytochemical processes incidental to the phenomenon of "selective neuronal death", which can be readily detected by the Nauta method. PMID- 1510247 TI - The generation and changing retinal distribution of displaced amacrine cells in Bufo marinus from metamorphosis to adult. AB - The generation and retinal distribution of displaced amacrine cells (DAs) were studied from metamorphosis to adult in the cane toad Bufo marinus. Displaced amacrine cells were identified by inducing chromatolytic changes in ganglion cells (GCs) following optic nerve section. Cells that did not chromatolyse in the ganglion cell layer (GCL) of the retina were regarded as DAs. The number of DAs increased considerably from an estimated 10,000 at metamorphosis to 211,000 in the adult toad, and was accompanied by a substantial decrease of average cell density. In contrast to the reported 6:1 cell density gradient of all cells of the GCL in adult toad (Nguyen and Straznicky 1989) only a shallow 1.6:1 density gradient of DAs from the visual streak to the dorsal and ventral retinal margins was detected. Consequently, the incidence of DAs increased from 15% of all cells of the GCL in the visual streak to 30% in the dorsal and ventral peripheral retina. These results indicate that the ratio of the newly generated DAs and GCs at the ciliary margin must be changing during development. More GCs are generated before and around metamorphosis then DAs, in contrast to the relative increase of the percentage of DAs generated after metamorphosis. The possible control of the numbers of DAs in the GCL is discussed. PMID- 1510248 TI - Types of callosally projecting nonpyramidal neurons in rat visual cortex identified by lysosomal HRP retrograde labeling. AB - Callosally projecting neurons, labeled following injection of horseradish peroxidase (HRP) into the 17/18a border of the contralateral hemisphere, have been examined by light and electron microscopy. These neurons exhibit two types of horseradish peroxidase labeling: either a diffuse, Golgi-like labeling, or a granular, punctate labeling. The punctate type of HRP-labeling is the predominant form in nonpyramidal neurons, while pyramidal neurons frequently display either diffuse or punctate labeling. Only punctately labeled neurons have been examined in this study. Light microscopic analyses of 1-microns sections show that in the heavily labeled zone at the area 17/18a border approximately 9% of all of the cells in layer II/III are callosally projecting nonpyramidal cells, and 70% of them are callosally projecting pyramidal cells. Light and electron microscopic examinations indicate that the nonpyramidal neurons are a heterogeneous group which consists of small multipolar neurons, large multipolar neurons, small bipolar neurons, and large bipolar neurons. To investigate the ultrastructural appearance of the punctate HRP labeling, selected neurons have been examined in thin sections. In the electron microscope, the tetramethylbenzidine (TMB) reaction product appears as electron-dense crystals, while the diaminobenzidine (DAB) reaction product appears as dark, electron-dense material which fills the lysosomes. These lysosomes occasionally have a halo of reaction product, but often they are not morphologically distinguishable from dark lysosomes present within neurons from control animals in which the darkening results from staining the thin sections with lead citrate and uranyl acetate. However, labeled neurons possess more dark lysosomes than neurons from control animals. These additional dark lysosomes presumably contain the HRP reaction product visible by light microscopy. PMID- 1510249 TI - Communication compartments in the axial mesoderm of the chick embryo. AB - Intracellular microinjection of the fluorescent tracer Lucifer Yellow into mesoderm cells along the rostrocaudal axis of the early chick embryo has revealed compartments where the intercellular diffusion of dye, presumably via gap junctions, is restricted at the borders between groups of cells. Cells in the segmental plate were dye-coupled, as were cells forming the epithelial somites. However, dye-coupling was not observed between different somites, nor was it observed between the outer epithelial cells and the cells in the somitocoele. On dispersal of the somite, dermatome cells were dye-coupled. However, sclerotome cells were found to be divided into rostral and caudal compartments separated by a group of cells bordering the intrasclerotomal fissure (of von Ebner) that also exhibited dye-coupling, restricted primarily to cells along the fissure. Some of these compartment borders can be accounted for by the presence of a morphological barrier which reduces cell-cell contact, but others are more difficult to explain, as there appears to be extensive cell-cell contact across the border. This would be analogous to some compartments found in insects. Some of the compartments also have borders similar to those described by cell lineage studies. The results also indicate that dye-coupling becomes restricted in a spatial and temporal manner as the mesodermal cells mature. PMID- 1510250 TI - Pharmacology of hemostasis in the surgical patient. PMID- 1510251 TI - Adenosine for controlled hypotension: systemic compared with intracoronary infusion in dogs. AB - We hypothesized that either through local myocardial or systemic effects, adenosine could be used to control hypotension during ischemia. Therefore, we compared the effects of systemic with intracoronary infusion of adenosine on myocardial hemodynamics and metabolism during ischemia in 27 dogs. Left anterior descending artery (LADa) flow was measured and the LADa constricted by a micrometer to restrict resting flow by 50%, 75%, and 100%. Adenosine was infused either systemically (n = 9), to maintain mean aortic pressure at 50-60 mm Hg, or directly into the LADa (n = 9), to create maximal coronary hyperperfusion; no adenosine was infused in the control group (n = 9). With systemic adenosine, during each constriction aortic pressure, left ventricular first derivative (LV dP/dt), and heart rate (HR) decreased: aortic pressure by 56.1% +/- 2.9% (mean +/ SEM), LV dP/dt by 36.2% +/- 2.2%, systemic resistance by 42.7% +/- 5%, and HR by 38.7% +/- 3% during 50% constriction (P less than 0.05 for each variable). Intracoronary adenosine decreased only aortic pressure, LV dP/dt, and HR, all to a lesser extent: aortic pressure by 5% +/- 2.8%, LV dP/dt by 15% +/- 1.2%, and HR by 4.6% +/- 1.7% (P less than 0.05, compared with systemic adenosine for each variable). With systemic adenosine only in the nonischemic area, regional myocardial blood flow increased and remained high, from 224.6 +/- 65.2 to 342 +/- 46.2 mL.min-1.100 g-1 during 50% constriction (P less than 0.05); with intracoronary adenosine, ischemic zone regional myocardial blood flow increased, but not consistently. In the ischemic area, O2 consumption was less with than without systemic adenosine; also, lactate flux production was less positive ( 60.2 +/- 37.6 compared with 80.3 +/- 20.2 mmol.min-1.100 g-1 x 10(-3) during 50% constriction; P less than 0.05). Systemic infusion of adenosine during coronary hypoperfusion improves regional metabolism during ischemia and, thus, may mitigate myocardial ischemia. The mechanism by which systemic infusion improves metabolic status may be by decreases in both systemic pressure and systemic vascular resistance. PMID- 1510252 TI - Effect of thoracic epidural anesthesia combined with general anesthesia on segmental wall motion assessed by transesophageal echocardiography. AB - Patients scheduled for vascular surgery are considered at risk for perioperative cardiac complications. Choice of anesthetic in such patients is guided by a desire not to adversely affect myocardial function. On the basis of data from laboratory studies, thoracic epidural anesthesia (TEA) has been advocated to prevent myocardial ischemia. The aim of this study was to assess whether TEA combined with general anesthesia has any effect on segmental wall motion (SWM) monitored by transesophageal echocardiography in these patients. Patients received alfentanil, midazolam, vecuronium, and 50% N2O in oxygen, and ventilation was controlled after orotracheal intubation; 12.5 mL of 2% lidocaine HCl was injected through an epidural catheter placed at T6-7 or T7-8. Hemodynamic measurements and transesophageal echocardiographic recordings were obtained before and 10, 20, 30, 40, and 60 min after lidocaine injection. Segmental wall motion was graded a posteriori by two independent experts on a predetermined scale (from 1 = normal to 5 = dyskinesia). A decrease greater than or equal to 2 grades was considered an SWM abnormality indicative of ischemia. Thoracic epidural anesthesia induced a decrease in systemic arterial blood pressure, heart rate, and cardiac index. The SWM score decreased slightly from 1.34 +/- 0.68 to 1.27 +/- 0.64 (mean +/- SD) (at 10 and 20 min, respectively) (P less than 0.05). Patients were a posteriori analyzed according to whether they had documented coronary artery disease or not. The SWM score before TEA was significantly higher in patients with documented coronary artery disease (1.51 +/- 0.88 vs 1.17 +/- 0.51, respectively; P less than 0.05) and did not change significantly after TEA.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1510253 TI - Role of systemic arterial pressure, heart rate, and derived variables in prediction of severity of myocardial ischemia during acute coronary occlusion in anesthetized dogs. AB - The present study examined the postulate that the quotient of mean systemic arterial pressure and heart rate predicts the severity of myocardial ischemia during occlusion of the left anterior descending coronary artery. Studies were performed in open-chest fentanyl-anesthetized dogs before and during halothane (n = 8) or isoflurane (n = 8) anesthesia. The pressure-rate quotient (PRQ) decreased significantly in both groups during incremental increases in halothane or isoflurane to 68% and 57% of control values at 0.5 MAC and to 41% and 38% at 1.5 MAC for halothane and isoflurane, respectively. Myocardial lactate production was unchanged from the ischemic region, and no correlation between the PRQ and myocardial lactate production was observed. In contrast, heart rate correlated significantly (r = 0.376; P less than 0.05) with lactate production. The product of systolic systemic arterial pressure and heart rate (rate-pressure product) correlated with blood flow (r = 0.493; P less than 0.001) and with oxygen consumption (r = 0.571; P less than 0.001) in the normal myocardium. A weak correlation (r = 0.330; P less than 0.05) of rate-pressure product with myocardial lactate production from the ischemic region was observed. There were no correlations between the PRQ and myocardial lactate production from the ischemic region or indices of blood flow distribution (i.e., inner/outer ratio in the ischemic region or ischemic/normal ratio). The relationship of hemodynamic variables to measurements of regional myocardial metabolism was independent of background anesthetic agent of depth of anesthesia. The current data suggest that heart rate changes are weakly predictive of severity of myocardial ischemia.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1510254 TI - Should all children with suspected or confirmed malignant hyperthermia susceptibility be admitted after surgery? A 10-year review. AB - Children otherwise suitable for same-day discharge may be admitted to the hospital solely because they are known or suspected to be malignant hyperthermia susceptible (MHS). To determine whether their hospitalization is necessary, the medical charts of 303 children labeled MHS who had undergone surgery with anesthesia free of malignant hyperthermia-triggering agents on 431 occasions between 1981 and 1990 were reviewed. Eighteen of these patients (25 cases) who were subsequently identified as biopsy-negative were excluded from the study. We recorded the reason for the MHS label and the perioperative management and outcome of the cases. Fifty-eight percent of procedures were followed by hospital admission solely because of the patient's MHS label. None of the 25 children (33 cases) with biopsy-proven malignant hyperthermia developed intraoperative or postoperative pyrexia. Ten children suspected to be MHS developed pyrexia greater than 38.5 degrees C. These episodes were not considered to be malignant hyperthermia and were not treated with dantrolene. None of the remaining 275 patients exhibited any features of malignant hyperthermia, although one had an adverse reaction to radiologic contrast medium. On the basis of our retrospective analysis, postoperative admission to the hospital solely on the basis of the MHS label is not warranted. PMID- 1510255 TI - Metoclopramide reduces the incidence of vomiting after tonsillectomy in children. AB - The efficacy of intravenous metoclopramide in controlling vomiting in children after tonsillectomy was determined in a prospective randomized, double-blind investigation. One hundred two unpremedicated, ASA physical status I or II children between the ages of 1 and 15 yr who were undergoing surgical removal of the tonsils, with or without adenoidectomy, were studied. Anesthesia was induced either with halothane, nitrous oxide, and oxygen by mask or by intravenous thiopental and was maintained with halothane, nitrous oxide, oxygen, and intravenous morphine (0.1 mg/kg). Each child randomly received either 0.15 mg/kg of metoclopramide or saline solution placebo intravenously after transfer to the postanesthesia care unit. All episodes of vomiting were recorded for 24 h after completion of surgery. The incidence of vomiting in the saline solution group was 70%, compared with 47% in the metoclopramide group (P = 0.026). The authors conclude that the administration of intravenous metoclopramide in a dose of 0.15 mg/kg on arrival in the postanesthesia care unit significantly decreases the incidence of vomiting in children after tonsillectomy. PMID- 1510256 TI - Comparative effects of laryngeal mask airway and endotracheal tube insertion on intraocular pressure in children. AB - Intraocular pressure (IOP) measurements in children are frequently performed under halothane-nitrous oxide anesthesia; however, anesthesia face masks may limit access to the eyes, and tracheal intubation is associated with transient increases in IOP. Use of the laryngeal mask airway (LMA) permits the maintenance of a patent airway without the need for laryngoscopy and tracheal intubation. In a randomized study of 41 children, we compared the IOP, hemoglobin oxygen saturation, and hemodynamic responses to the insertion of an LMA or tracheal tube during a standardized steady-state anesthetic technique consisting of 1 MAC halothane and 66% nitrous oxide. Baseline measurements of IOP, hemoglobin oxygen saturation, heart rate, and arterial blood pressure were recorded and repeated within 15-30 s after insertion of the airway device and at 1-min intervals for 5 min. Insertion of the LMA required significantly less time (26 +/- 16 vs 39 +/- 17 s [mean +/- SD]) and was associated with higher hemoglobin oxygen saturation values compared with the tracheal intubation. The LMA did not increase IOP, heart rate, or arterial blood pressure above baseline values. In contrast, tracheal intubation was associated with significant increases of IOP, heart rate, and arterial blood pressure. We concluded that the laryngeal mask offers advantages over tracheal intubation and the face mask for airway management in patients undergoing IOP measurements. PMID- 1510257 TI - Epidural test dose and intravascular injection in obstetrics: sensitivity, specificity, and lowest effective dose. AB - The authors studied the sensitivity and specificity of several epidural test doses as markers of intravascular injection in laboring patients in a prospective double-blind, randomized study. Fifty-nine parturients were assigned randomly to receive an intravenous injection of either normal saline solution (3 mL, NS group) or 1.5% lidocaine with epinephrine 1:200,000 (1 mL, EPI-5 group; 2 mL, EPI 10 group; or 3 mL, EPI-15 group). The EPI-5 and EPI-10 doses were diluted to 3 mL volume with normal saline solution. All injections were given during uterine diastole. Maternal heart rate was monitored with a pulse oximeter. An observer who was unaware of the study treatment recorded the baseline and the peak maternal heart rate within the first minute after the injection and questioned the patient about tinnitus, dizziness, metallic taste, and palpitations. He then recorded his opinion as to whether the patient had received the saline or the test solution. Analysis of the maternal heart rate showed an average increase (baseline-to-peak criterion) of 8 +/- 10 beats/min (mean +/- SD) in the NS group. In the other groups, the increase was 21 +/- 8 (EPI-5 group), 31.5 +/- 13 (EPI-10 group), and 29 +/- 9 beats/min (EPI-15 group). A baseline-to-peak criterion of greater than 10 beats/min identified all intravascular injections in the EPI-15 (by design) and EPI-10 groups (15 of 15 and 14 of 14, respectively) with a sensitivity of 100%. Specificity was 73% (11 of 15 true negatives).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1510258 TI - Headache after spinal anesthesia for cesarean section: a comparison of the 27 gauge Quincke and 24-gauge Sprotte needles. AB - A high incidence of postdural puncture headache (PDPH) occurs after spinal anesthesia for cesarean section. To examine this problem, a study was conducted with the recently developed 24-gauge Sprotte and 27-gauge Quincke needles in patients undergoing elective and emergency cesarean section (n = 298). The needle to be used was assigned in a random manner: group I, 27-gauge Quincke (n = 147); group II, 24-gauge Sprotte (n = 151). During the postoperative period, patients were visited daily and asked specifically about the presence and severity of headache. The overall incidence of PDPH was 2% (n = 6), five in the Quincke group (3.5%) and one in the Sprotte group (0.7%). There was no significant difference in the incidence of PDPH between the two groups. Five headaches were classified as mild, and only one was moderate to severe. All headaches resolved quickly with conservative management and without blood patch. The authors conclude that the choice between a 27-gauge Quincke and a 24-gauge Sprotte needle does not influence the incidence of PDPH after spinal anesthesia for cesarean section. PMID- 1510259 TI - Interscalene brachial plexus block for shoulder surgery: a proximal paresthesia is effective. AB - This study was designed to determine whether the location of paresthesias is related to the success of interscalene blocks in providing anesthesia for shoulder surgery. Interscalene blocks were performed in 45 patients presenting for elective shoulder surgery. Interscalene injections of 33-55 mL of 1.5% mepivacaine with epinephrine were performed after the first elicited paresthesia to the shoulder, arm, forearm, or hand. In 20 patients (45%), the initial elicited paresthesia was to the shoulder, whereas in 25 patients (55%), the first paresthesia was reported as distal to the shoulder. All patients developed brachial plexus anesthesia adequate for shoulder surgery. The time-course of onset of motor block as evaluated at the shoulder and elbow was not different between patients with shoulder paresthesias and those with more distal paresthesias. Handgrip strength was quantitatively evaluated with a dynamometer, and both paresthesia groups showed similar decrements in hand strength except at the end of the measurement period, when patients with distal paresthesias had a significantly weaker handgrip than patients with shoulder paresthesias. We recommend that paresthesias to the shoulder be accepted in performing interscalene blocks for patients undergoing shoulder surgery. PMID- 1510260 TI - Influence of volume on the spread of local anesthetic-methylene blue solution after injection for intercostal block. AB - The purpose of this study was to evaluate the influence of the volume of methylene blue-local anesthetic on the spread of the injectate along the costal pleura. Twenty patients undergoing elective thoracotomy were studied. Twelve patients received intercostal nerve injection with 10 mL of 0.5% bupivacaine with methylene blue (10-mL group), and eight patients received 5 mL of 0.5% bupivacaine with methylene blue (5-mL group). The area of spread of the methylene blue was measured after the pleural cavity was incised. The 10-mL group had a mean area of spread of 51.1 cm2 as opposed to 17.6 cm2 for the 5-mL group (P less than 0.05). In the 10-mL group, eight patients had bupivacaine-methylene blue spread to two intercostal spaces, three patients to three intercostal spaces, and one patient to four intercostal spaces. In the 5-mL group, seven patients had bupivacaine methylene blue spread confined to one intercostal space and one patient to two intercostal spaces. We conclude that a potential anatomic space exists between the costal pleura and the internal intercostal muscle and that the spread of local anesthetic after intercostal nerve block injection is volume dependent. PMID- 1510261 TI - Repeated intrathecal injections of dezocine produce antinociception without evidence for neurotoxicity in the rat: a study of morphometric evaluation of spinal cord histology. AB - This study was designed to determine the antinociceptive and spinal cord histologic effects of a new agonist/antagonist opioid drug dezocine. This drug was injected intrathecally in rats at a dose of 50 or 125 micrograms twice daily for 14 days. The tail-flick test showed that the antinociceptive effect declined gradually, with no detectable effects by day 14. Quantitative histologic techniques and light and electron microscopy showed that neither dose, compared with vehicle, created any morphologic changes in the spinal cord that could be attributed to a neurotoxic or otherwise degenerative effect of the drug. In conclusion, dezocine is a drug that gives rise to sustained antinociceptive effects when administered intrathecally and causes no morphologic changes in the rat spinal cord that could be indicative of neurotoxic potential. PMID- 1510262 TI - A trial of desmopressin to reduce blood loss in patients undergoing spinal fusion for idiopathic scoliosis. AB - Desmopressin (DDAVP) has been reported to reduce bleeding in patients undergoing spinal fusion. To evaluate its efficacy in normal patients, 30 healthy young patients (ASA physical status I or II) undergoing spinal fusion for idiopathic scoliosis were randomly allocated to receive either 100 mL of physiologic saline solution (placebo group) or DDAVP (10 micrograms/m2 of body surface area) (DDAVP group) in a prospective, double-blind trial. Intraoperative blood loss was measured by weighing sponges and suction drainage and postoperative bleeding by wound drainage. The amount of blood loss expressed as a percent of the estimated blood volume was similar in both groups during the intraoperative period (67.0% +/- 28.8% [mean +/- SD] placebo group vs 57.4% +/- 26.5% DDAVP group), the postoperative period up to 24 h (32.5% +/- 6.4% placebo group vs 31.1% +/- 10.6% DDAVP group), and both periods (94.3% +/- 29.4% placebo group vs 88.2% +/- 30.7% DDAVP group). With the dose used in our study, we conclude that DDAVP does not reduce surgical bleeding in patients undergoing spinal fusion for idiopathic scoliosis. PMID- 1510263 TI - Effect of desmopressin acetate on hindlimb perfusion pressure in rats: what is the mechanism? AB - Desmopressin acetate (DDAVP) is a synthetic analogue of vasopressin used to promote hemostasis and reduce postoperative blood loss. Desmopressin acetate can cause hypotension in humans. Our study evaluated the hemodynamics of rapid administration of DDAVP into the isolated hindlimb in live rats and assessed this response after pretreatment with various antagonists. Thirty male Sprague-Dawley rats (350-450 g) were given intraperitoneal pentobarbital anesthesia (50 mg/kg). Perfusion was set at a rate that gave a control mean hindlimb perfusion pressure (HPP) of 100-120 mm Hg. Rats were assigned to five groups (N = 5, each group), with each rat serving as its own control. As a control, saline solution (in volumes equivalent to those used for the antagonists) was injected into the hindlimb preparation before the agonist injections. Each group received both the clinical preparation of DDAVP (i.e., with preservative) and a laboratory preparation of DDAVP in doses of 0.3-3 ng. Group 1 was tested before and after injection of saline solution control; group 2, before and after propranolol (0.5 mg/kg); group 3, before and after meclofenamate (1.5 mg/kg), a cyclooxygenase inhibitor; group 4, before and after nitroarginine (5 mg/kg) an inhibitor of nitric oxide synthesis; and group 5, before and after atropine sulfate (1 mg/kg). Chlorobutanol (25-75 micrograms), the preservative in the clinical preparation of DDAVP, was tested for changes in HPP in five rats similarly prepared. Systemic mean arterial pressure remained constant during the study. The HPP decreased with increasing doses of the clinical preparation of DDAVP, compared with saline solution controls, whereas no change occurred with the laboratory preparation of DDAVP.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1510264 TI - Blood flow and tissue oxygen pressures of liver and pancreas in rats: effects of volatile anesthetics and of hemorrhage. AB - The object of this investigation was to compare the effects of volatile anesthetics and of hemorrhage at comparable arterial blood pressures on splanchnic blood flow (radioactive microspheres) and tissue oxygenation of the liver and pancreas (surface PO2 [PSO2] electrodes). In contrast to earlier studies, we did not use identical minimum alveolar anesthetic concentration multiples as a reference to compare volatile anesthetics; rather, we used the splanchnic perfusion pressure. Under general anesthesia (intravenous chloralose) and controlled ventilation, 12 Sprague-Dawley rats underwent laparotomy to allow access to abdominal organs. Mean arterial pressure was decreased from 84 +/- 3 mm Hg (mean +/- SEM) at control to 50 mm Hg by 1.0 +/- 0.1 vol% halothane, 2.2 +/- 0.2 vol% enflurane, and 2.3 +/- 0.1 vol% isoflurane in a randomized sequence. For hemorrhagic hypotension, blood was withdrawn gradually until a mean arterial pressure of 50 mm Hg was attained. Volatile anesthetics and hemorrhage reduced cardiac output, and hepatic arterial, portal venous, and total hepatic blood flows by comparable degrees. Mean hepatic PSO2 decreased significantly from 30.7 +/- 2.6 mm Hg at control to 17.4 +/- 2 and 17.5 +/- 2 mm Hg during enflurane and isoflurane (each P less than 0.05) anesthesia, respectively. The decrease to 11.5 +/- 2.5 mm Hg was more pronounced during halothane anesthesia. Hemorrhagic hypotension was associated with the lowest hepatic PSO2 (3.4 +/- 1.3 mm Hg) and the highest number of hypoxic (0-5 mm Hg 86%) and anoxic PSO2 values (0 mm Hg 46%). Pancreatic blood flow and oxygenation remained unchanged from control during halothane and enflurane administration, whereas isoflurane increased both variables. Hemorrhagic hypotension slightly reduced pancreatic flow (-8%) but significantly decreased PSO2 from 58 +/- 5 mm Hg at control to 36 +/- 3 mm Hg, with 7% of all measured values in the hypoxic range. Thus, volatile anesthetics preserved pancreatic but not hepatic blood flow and tissue oxygenation in this rat model. Despite comparable effects on perfusion, the PSO2 of the liver and pancreas was the least during hemorrhagic hypotension compared to that with the anesthetics. Because the volative anesthetic-induced hypotension has such a different effect on splanchnic tissue oxygenation compared with hemorrhagic induced hypotension, the authors conclude that the method of inducing hypotension may have different effects on oxygenation of various tissues. PMID- 1510265 TI - Osmolalities of propylene glycol-containing drug formulations for parenteral use. Should propylene glycol be used as a solvent? AB - Propylene glycol (PG) is a widely used vehicle for water-insoluble drugs. Injection of drugs formulated with this solvent often results in pain, thrombosis, or thrombophlebitis that can be reduced by premedication with local anesthetics or opioids. Because osmolality and pH that are unphysiologic may cause these adverse effects, we assessed the contribution of PG to the osmolality of parenteral drug formulations. Osmolality of PG measured in distilled water showed that PG content and osmolality were directly related: 2% wt/vol PG, 264 mOsm/L; 100% PG, 15, 200 mOsm/L. The osmolalities of commercially available preparations of drugs dissolved in PG ranged from 365 mOsm/L (2% PG content) to 12,800 mOsm/L (83.46% PG), with most above 1000 mOsm/L. Replacement of PG by a solvent with lower osmolality in Germany has effectively reduced the incidence of side effects for one drug. Until PG can be replaced in drugs, we recommend diluting drugs in a large volume of saline solution; this may help to minimize the undesirable effects of this solvent. PMID- 1510266 TI - Sevoflurane is biotransformed by guinea pig liver slices but causes minimal cytotoxicity. AB - Guinea pig liver slices were used to evaluate the biotransformation and hepatotoxic potential of sevoflurane. Precision-cut liver slices (250-300 microns thick) were incubated in sealed roller vials in buffer at 37 degrees C under 95% O2. Sevoflurane was added to produce 0.9 or 2.1 mM medium concentrations. After incubation (6-24 h), the intracellular K+ content and protein synthesis were determined, along with the defluorination of sevoflurane. Isoflurane was included for comparative purposes. Sevoflurane (2.1 mM) and isoflurane (2.3 mM) had no effect on slice K+ content, but both anesthetics depressed protein synthesis. The biotransformation of sevoflurane was maximal at 95% O2, with threefold more F- produced from sevoflurane than isoflurane. Sevoflurane appears to have a minimal effect on the guinea pig liver slices, which is consistent with in vivo studies in which minimal or no hepatotoxicity has been observed. PMID- 1510267 TI - A cysteine-for-arginine substitution (R614C) in the human skeletal muscle calcium release channel cosegregates with malignant hyperthermia. AB - A point mutation in the human gene for the skeletal muscle calcium release channel (ryanodine receptor [RYR1]) correlates with inheritance of malignant hyperthermia in a family of Northern European descent. The substitution of thymine for cytosine at position 1840 of the RYR1 transcript results in a cysteine-for-arginine substitution at position 614 (R614C) of the amino acid sequence. The mutation was absent in 59 normal individuals from the general population, in 61 additional unrelated malignant hyperthermia-susceptible patients, and in 18 patients with malignant hyperthermia associated with other inherited or congenital diseases. Together with reports of an equivalent mutation in six susceptible pig strains and an identical mutation in one other human pedigree, these findings suggest that the cysteine-for-arginine mutation represents a shared calcium release channel pathogenesis between porcine malignant hyperthermia and a subset of mutations responsible for the human malignant hyperthermia syndrome. PMID- 1510268 TI - Radiographic examination of catheter position in restricted sacral block after continuous spinal anesthesia. PMID- 1510269 TI - Patient-controlled spinal analgesia for postoperative pain control. PMID- 1510270 TI - A rare case of perineal pain: intestinal perforation caused by a press-through package. PMID- 1510271 TI - Superior laryngeal nerve block as a supplement to total intravenous anesthesia for rigid laser bronchoscopy in a patient with myasthenic syndrome. PMID- 1510272 TI - Should the anesthesiologist estimate the patient's weight? PMID- 1510273 TI - Ralph Waters' ghost and the AUA. PMID- 1510274 TI - Suicide attempt after anesthesia. PMID- 1510276 TI - Complete tolerance to opioids. PMID- 1510275 TI - How does epidural anesthesia and analgesia influence perioperative coagulability? PMID- 1510277 TI - Differential awakening. PMID- 1510278 TI - Is the "kneeling" prone position as dangerous as the sitting position for the development of venous air embolism? PMID- 1510279 TI - A special surgical technique leads to venous air embolism during neurosurgery of the spine. PMID- 1510280 TI - Scientific approach to presenting and summarizing data. PMID- 1510281 TI - Esterase nomenclature: a confusing topic. PMID- 1510282 TI - A simple replacement for the pulmonary artery catheter balloon syringe. PMID- 1510283 TI - Refractory periorbital edema in a 29-year-old man. AB - A 29-year-old man developed periorbital edema which was initially diagnosed as angioedema. Further clinical investigation by orbital CT and orbital biopsy showed this to be orbital pseudotumor. Immunofluorescence staining for major basic protein clearly demonstrated tissue eosinophilia and extracellular major basic protein deposition. Orbital pseudotumor can mimic angioedema or allergic rhinoconjunctivitis and should be familiar to allergists and primary care physicians. The demonstration of striking extracellular major basic protein in biopsy specimen implicates a role for eosinophils in the pathogenesis of this disease. PMID- 1510284 TI - Fatal and near fatal asthma. AB - Despite the recent development of apparently effective asthma drugs, the number of deaths from asthma has not declined. The authors tried to establish an optimal strategy for the prevention of acute asthmatic death by analyzing the circumstances of acute fatal or near-fatal asthma. Data were collected from 51 adult patients admitted to Bokutoh Tertiary Emergency Center due to acute asthma between November 1985 and May 1990 and 38 asthmatic patients admitted to Yokohama City Hospital in 1990. Pre-admission data were obtained through interviews with the patients, their families, or doctors who had seen them. A total of 89 patients were classified into three subgroups: group 1 consisted of patients dead on-arrival (DOA); group 2, non-DOA patients with disturbed consciousness; and group 3, patients with less severe episodes. Little background information was significantly different among groups, but symptomatic episodes in group 1 patients tended to occur more rapidly. The speed of onset of the episodes was also dependent on the asthma control status. Prehospital care of groups 1 and 2 patients was very poor despite severity of the symptoms. All patients in groups 2 and 3 were successfully treated and discharged, but five of the 26 patients in group 2 died during follow-up periods. Prognosis of patients after discharge appeared to be dependent upon asthma control status before the acute episodes. It was concluded that acute fatal or near fatal asthma could occur in apparently low risk patients as well as high-risk ones. It was also suggested that the optimal strategy for preventing asthma deaths might be variable. PMID- 1510285 TI - Atopy and bronchial responsiveness in random population sample of 527 children and adolescents. AB - The relationship between bronchial responsiveness, lung function, and results of skin prick testing was studied in 527 children and adolescents from Copenhagen. All participants completed a questionnaire concerning allergic symptoms (asthma, rhinitis, atopic dermatitis, and urticaria). Furthermore, skin prick test reactivity to nine common aeroallergens, lung function, serum IgE and bronchial responsiveness to histamine and exercise were measured. A total of 53 subjects were atopic, (skin prick 3+), 105 subjects had moderate skin reactivity (1-2+), and 366 subjects had no signs of atopic disease (prick test negative); 58% of the subjects with skin test reactivity (1-3+) were asymptomatic. Increasing degree of atopy was correlated significantly with symptoms such as asthma, rhinitis, dermatitis, and urticaria (P less than .001); increasing level of IgE (P less than .001); month of birth (P = .001); and family history of allergic diseases (P less than .05). The most important markers for the degree of bronchial responsiveness to inhaled histamine were the presence of respiratory symptoms (P less than .001), the degree of atopy (P = .001), a history of asthma in at least two first degree relatives (P less than .01), and the skin reactivity to house dust mites (P = .001), horse epithelium (P = .01), Alternaria iridis, and dog epithelium (P less than .05). In contrast, the degree of bronchial responsiveness to exercise was significantly correlated with asthma (P less than .001), the level of IgE (P less than .05), month of birth (P less than .001), and birth weight (P less than .05).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1510286 TI - Effect of astemizole on allergic asthma. AB - In a placebo-controlled, double-blind, crossover study with a washout phase of 2 months between each treatment period, single daily doses of 10 and 30 mg of astemizole were given to 12 patients with extrinsic asthma during 28 consecutive days. Albuterol was allowed as concurrent medication when needed. On days 0, 7, and 28 specific bronchial provocation with Dermatophagoides pteronyssinus and cutaneous tests with histamine and D. pteronyssinus extracts were carried out. The requirements of beta-agonist inhalations and the number of bronchospasm episodes were recorded throughout the study period. Inhibition of allergen induced bronchoconstriction appeared on day 7 with 30-mg doses of astemizole, while it was not observed until day 28 with 10-mg doses. Wheal responses caused by histamine were reduced only after active treatment. The wheal response to the highest allergen concentration was reduced on days 7 and 28 after 30 mg of astemizole, whereas doses of 10 mg only caused a reduction on day 28. It is concluded that astemizole could be useful as a therapeutic agent in the treatment of certain types of asthma. PMID- 1510287 TI - Chediak-Higashi syndrome: clinical, hematologic, and immunologic improvement after splenectomy. AB - A 10-year-old boy with Chediak-Higashi syndrome in accelerated phase failed to respond to treatment with ascorbic acid, vincristine, and prednisone. Splenectomy resulted in clinical, hematologic, and immunologic improvement: his leukocyte chemotactic and phagocytic functions returned to normal. We suggest that splenectomy be considered in treatment of the accelerated phase of Chediak Higashi syndrome unresponsive to other forms of therapy. PMID- 1510288 TI - Immunoassay of specific IgE: low level assays require measurement of allergen specific assay background. AB - The allergen-specific backgrounds of a paper disk radioimmunoassay (RIA) system and a cellulose sponge fluorescent enzyme immunoassay (FEIA) system were evaluated using three inhalants, timothy, short ragweed, and cat, with reagents obtained from the same manufacturer. Radioimmunoassay was performed with Phadebas RAST reagents by the modified RAST method, and FEIA by the Pharmacia CAP System. Horse serum, 5% HSA, assay diluent, and serum pools from nonallergic and allergic patients, were assayed. The lower limit of detection (LLD) was defined using both the Z distribution (as is conventional) and the t distribution. The solid phases, analytes, and assays differed (p less than .001) in background results. For RIA, background was lowest for timothy and highest for cat; for FEIA, background was lowest for cat and highest for short ragweed. For RIA, background assessed with the allergic serum pool was higher than the other analytes; for FEIA, responses of the five analytes did not differ. For timothy and short ragweed, background of RIA was lower than FEIA. For FEIA, the highest LLD calculated using the Z distribution was 11 SD lower than the manufacturer's recommended quantitative cutoff; for RIA, the highest LLD calculated was 2.5 SD higher than the recommended analytic cutoff. The analytic false positive rate for RIA may differ between allergic and nonallergic patient populations. Laboratories reporting results near either assay's background should set LLD based on assay of allergen specific negative controls in each assay run. PMID- 1510289 TI - Buckwheat-induced anaphylaxis: a case report. AB - Buckwheat (Fagopyrum schulentum) is not taxonomically related to wheat and other cereal grains. Buckwheat flour is used as a wheat substitute in breads, biscuits, pancakes, and crepes. Occupational exposure to buckwheat flour has been associated with rhinitis, conjunctivitis, contact urticaria, and occupational asthma. We present a patient who developed urticaria and hypotension after ingestion of buckwheat crepes. Skin testing by the prick technique revealed 3+ positive reaction to buckwheat with negative reactions to other foods including wheat, egg white, and milk. RAST for anti-buckwheat IgE was strongly positive. Buckwheat ingestion is a potential cause of food-related anaphylaxis. There does not appear to be cross-reactivity between buckwheat and wheat allergy. PMID- 1510291 TI - The "Annals of Allergy" 1965-82. PMID- 1510290 TI - Asthma mortality, east and west. PMID- 1510292 TI - Anaphylaxis. AB - Systemic anaphylaxis results from the sudden release of mediators from a variety of inflammatory cells. Most reactions are due to insect stings, food allergy, immunotherapy injections, or pharmaceutical products. Anaphylaxis is easily recognized in most cases, although persons found unresponsive or who exhibit hypotension without urticaria or cutaneous angioedema present special diagnostic problems. Most reactions respond promptly to aggressive therapy, although fatalities occasionally occur. Optimal long-term care of patients with anaphylaxis involves accurate identification of triggering agents, education regarding allergen avoidance, and self-administration of epinephrine in case of future reactions. PMID- 1510293 TI - A method for pneumatically inserting an array of penetrating electrodes into cortical tissue. AB - The goal of this research was to find a practical means by which an array of 100 needle-shaped electrodes could be implanted into the cerebral cortex with minimal brain tissue trauma. It was found that insertion of these structures into cortical tissues could only be performed using high insertion speeds. A pneumatically actuated impact insertion system has been developed that is capable of inserting an electrode array into feline brain tissue at speeds from about 1 to 11 m/s. We found that a minimum array insertion speed of 8.3 m/s was necessary for a complete, safe insertion of all 100 electrodes in the array to a depth of 1.5 mm into feline cortex. The performance of the impact insertion system is discussed in terms of a simplified representation of cortical tissue. PMID- 1510294 TI - A glass/silicon composite intracortical electrode array. AB - A new manufacturing technique has been developed for creating silicon-based, penetrating electrode arrays intended for implantation into cerebral cortex. The arrays consist of a 4.2 mm x 4.2 mm glass/silicon composite base, from which project 100 silicon needle-type electrodes in a 10 x 10 array. Each needle is approximately 1,500 microns long, 80 microns in diameter at the base, and tapers to a sharp point at the metalized tip. The technique used to manufacture these arrays differs from our previous method in that a glass dielectric, rather than a p-n-p junction, provides electrical isolation between the individual electrodes in the array. The new electrode arrays exhibit superior electrical properties to those described previously. We have measured interelectrode impedances of at least 10(13) omega, and interelectrode capacitances of approximately 50 fF for the new arrays. In this paper, we describe the manufacturing techniques used to create the arrays, focusing on the dielectric isolation technique, and discuss the electrical and mechanical characteristics of these arrays. PMID- 1510295 TI - Simulation of a phosphene-based visual field: visual acuity in a pixelized vision system. AB - A visual prosthesis for the blind using electrical stimulation of the visual cortex will require the development of an array of electrodes. Passage of current through these electrodes is expected to create a visual image made up of a matrix of discrete phosphenes. The quality of the visual sense thus provided will be a function of many parameters, particularly the number of electrodes and their spacing. We are conducting a series of psychophysical experiments with a portable "phosphene" simulator to obtain estimates of suitable values for electrode number and spacing. The simulator consists of a small video camera and monitor worn by a normally sighted human subject. To simulate a discrete phosphene field, the monitor is masked by an opaque perforated film. The visual angle subtended by images from the masked monitor is 1.7 degrees or less, depending on the mask, and falls within the fovea of the subject. In the study presented here, we measured visual acuity as a function of the number of pixels and their spacing in the mask. Visual acuity was inversely proportional to pixel density, and trained subjects could achieve about 20/26 visual acuity with a 1024 pixel image. We conclude that 625 electrodes implanted in a 1 cm by 1 cm area near the foveal representation of the visual cortex should produce a phosphene image with a visual acuity of approximately 20/30. Such an acuity could provide useful restoration of functional vision for the profoundly blind. PMID- 1510296 TI - A Barycentremetric study of the sagittal shape of spine and pelvis: the conditions required for an economic standing position. AB - The standing posture of 17 young men and women were studied using Barycentremeter measurements and full spine radiograph with a single referential system. These procedures provide in vivo measurements of the weight and center of weight supported by each vertebra and the coxofemoral joints. The relationship between the vertebra, the sacrum or the coxofemoral rotation axis and the center of weight they support, is displayed. The moment of the corresponding force may also be assessed. Mean values were computed and the relation with spine sagittal curves and pelvic parameters were studied. The position of the center of weight, in front of or behind the vertebra or the coxofemoral joints, requires an opposing muscle force to ensure mechanical stability. The load exerted on the vertebra cannot be precisely evaluated, but we can describe the way in which these loads vary when the spinal curves and the pelvic slope change. This study provides basic data suggesting that there is a tendency to maintain the body in the most economical position in terms of muscle fatigue and vertebral strain. Individual anatomical shapes and pelvic parameters of the pelvis induce corresponding specific sagittal curves of the spine. This concept is very useful for analysing pathological situations and devising appropriate treatment. PMID- 1510297 TI - The effect of convection on bidirectional peritoneal solute transport: predictions from a distributed model. AB - A distributed model of the peritoneum has been proposed as an alternative to the standard membrane model for describing peritoneal solute transport. The effect of convection on bidirectional peritoneal solute transport is studied theoretically using the distributed model. Approximate analytical and exact numerical solutions to the distributed model yield predictions similar to those when using a membrane model of peritoneal solute transport. Difficulties in interpretation of the membrane transport parameters may arise, however, when interstitial tissue, not the capillary wall, is the dominant diffusive solute transport resistance. Under such conditions the effect of convection on peritoneal solute transport is dependent on the transport direction. Moreover, predictions from the distributed model are similar to those for a membrane model containing two transport barriers in series. Thus, both the distributed model and a membrane model containing two serial transport barriers equivalently describe the effect of convection on bidirectional peritoneal solute transport. PMID- 1510298 TI - Induction of the acute-phase cytokine, hepatocyte-stimulating factor/interleukin 6, in the circulation of horses treated with endotoxin. AB - Because hepatocyte-stimulating factor/interleukin 6 (IL-6) is the principal inducer of acute-phase protein synthesis in the liver, quantification of its activity in blood provides an early and sensitive assessment of the acute-phase response. Circulating IL-6 activity was monitored in 4 adult horses for 72 hours after IV administration of endotoxin. In 4 experiments performed at weekly intervals and in randomized order, each horse was given endotoxin--1,000 30, 1, and 0 ng/kg of body weight. Plasma IL-6 activity was quantified as the ability to promote growth of the IL-6-dependent B-cell hybridoma, B13.29 clone B9. Interleukin-6 activity (171 +/- 10.2 U/ml) was found in all pretreatment plasma samples and was significantly (P less than 0.05) increased above baseline from 2 to 12 hours after 1,000 ng of endotoxin/kg was given and at 3 hours after 30 ng of endotoxin/kg was given. After 1,000- or 30-ng/kgt dosage of endotoxin, peak plasma IL-6 activity (10,128 +/- 4,096 and 1,555 +/- 1,326 U/ml, respectively) was observed for 3 hours. The IL-6 response of endotoxin-treated horses began about 1 hour after tumor necrosis factor appeared in the circulation, and its course closely approximated the endotoxin-induced febrile reaction. Significant increase in plasma IL-6 activity was not detected in horses given 1 ng of endotoxin/kg or control buffer. PMID- 1510299 TI - Plasma renin activity and aldosterone and vasopressin concentrations during incremental treadmill exercise in horses. AB - Six untrained mares were subjected to incremental treadmill exercise to examine exercise-induced changes in plasma renin activity (PRA) and plasma aldosterone (ALDO) and plasma arginine vasopressin (AVP) concentrations. Plasma renin activity, ALDO and AVP concentrations, and heart rate (HR) were measured at each step of an incremental maximal exercise test. Mares ran up a 6 degree slope on a treadmill set at an initial speed of 4 m/s. Speed was increased 1 m/s each minute until HR reached a plateau. Plasma obtained was stored at -80 C and later was thawed, extracted, and assayed for PRA and ALDO and AVP values by use of radioimmunoassay. Exercise caused significant increase in HR from 40 +/- 2 beats/min (mean +/- SEM) at rest to 206 +/- 4 beats/min (HRmax) at speed of 9 m/s. Plasma renin activity increased from 1.9 +/- 1.0 ng/ml/h at rest to a peak of 5.2 +/- 1.0 ng/ml/h at 9 m/s, paralleling changes in HR. Up to treadmill speed of 9 m/s, strong linear correlations were obtained between exercise intensity (and duration) and HR (r = 0.87, P less than 0.05) and PRA (r = 0.93, P less than 0.05). Heart rate and PRA reached a plateau and did not increase when speed was increased from 9 to 10 m/s. Plasma ALDO concentration increased from 48 +/- 16 pg/ml at rest to 191 +/- 72 pg/ml at speed of 10 m/s. Linear relation was found between exercise intensity (and duration) and ALDO concentration (r = 0.97, P less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1510300 TI - Use of progesterone in microspheres for maintenance of pregnancy in mares. AB - Administration of progesterone in poly(d-,l-lactide) microspheres was used to maintain pregnancy in mares after luteolysis was induced by treatment with prostaglandin F2 alpha at day 14 of pregnancy. Mares were given vehicle only (control, n = 6) or 0.75 g (n = 7), 1.5 g (n = 8), or 2.25 g (n = 5) of microencapsulated progesterone at days 12 and 22 of pregnancy. Serum progesterone concentrations were determined daily, and pregnancy was evaluated by transrectal ultrasonography on alternate days. Significantly (P less than 0.05) more mares given 1.5 or 2.25 g of progesterone (6 of 8 and 4 of 5 mares, respectively), but not those given 0.75 g (3 of 7 mares), maintained pregnancy through day 32, compared with control mares (0 of 6). Progesterone concentrations decreased significantly (P less than 0.025) in all groups after administration of prostaglandin F2 alpha at day 14, and significant (P less than 0.05) effects of time and treatment on progesterone concentrations were found between days 12 and 22, and 22 and 32. Although treatment with 1.5-g and 2.25-g doses of microencapsulated progesterone improved maintenance of pregnancy, compared with that of vehicle-treated controls, administration of 2.25 g of microencapsulated progesterone appeared to be most efficacious in maintenance of pregnancy during the study interval. PMID- 1510301 TI - Endotoxin-induced production of interleukin 6 by equine peritoneal macrophages in vitro. AB - A study was performed to determine whether equine peritoneal macrophages produce interleukin 6 (IL-6) in vitro in response to endotoxin. Peritoneal fluid was collected from 14 clinically normal adult horses and was used as the source of peritoneal macrophages. Macrophages from each horse were isolated and cultured separately in vitro in the absence or presence of various concentrations (0.5, 5, 500 ng/ml) of endotoxin (lipopolysaccharide from Escherichia coli 055:B5). Culture medium supernatants were collected after 3, 6, 12, and 24 hours' incubation and were frozen at -70 C until assayed for IL-6 activity. Supernatant IL-6 activity was determined by use of a modified colorimetric assay and the murine hybridoma cell line B 13.29 clone B.9, which is dependent on IL-6 for survival. Results indicated that equine peritoneal macrophages produce IL-6 in vitro and that supernatant medium IL-6 activity was significantly (P less than 0.05) increased by exposure to endotoxin. Significant (P less than 0.05) time and treatment effects on macrophage IL-6 production were apparent. The IL-6 activity peaked at 6 or 12 hours' incubation, then remained high through 24 hours' incubation, regardless of endotoxin exposure. Medium IL-6 activity during 3 and 6 hours' incubation was significantly (P less than 0.05) greater in macrophages exposed to 5 or 500 ng of endotoxin/ml than in those exposed to 0.5 ng of endotoxin/ml; however peak IL-6 activity was similar among all endotoxin concentrations. Endotoxin concentration did not have an effect on medium IL-6 activity from macrophages exposed to endotoxin for 12 or 24 hours. PMID- 1510302 TI - Effects of prostaglandin F2 alpha and leukotriene D4 on pupil size, intraocular pressure, and blood-aqueous barrier in dogs. AB - In each of 5 groups of dogs, 0.05 ml of 1 of the following solutions was injected into the anterior chamber of both eyes: phosphate-buffered saline solution, 0.001 microgram of prostaglandin F2 alpha (PGF2 alpha), 0.01 microgram of PGF2 alpha, 0.1 microgram of leukotriene D4 (LTD4), and 1 microgram of LTD4. A 10% solution of sodium fluorescein was injected IV (14 mg/kg of body weight) at the same time, and pupil size, intraocular pressure, and anterior chamber fluorescence were measured for 1 hour after injections. In a dose-dependent manner, PGF2 alpha was a potent miotic. A significant effect on intraocular pressure was not detected when the groups given PGF2 alpha were compared with the control group. When compared with LTD4, PGF2 alpha significantly (P less than 0.05) increased the breakdown of the blood-aqueous barrier, as evidenced by increased fluorescein leakage into the anterior chamber. Leukotriene D4 caused a decrease in pupil size only at 5 minutes, compared with that of the control group. Intraocular pressure was greater (but not significantly) in the group given 1 microgram of LTD4. PMID- 1510303 TI - Effect of bilateral stimulation on spinal evoked potentials in dogs. AB - We compared the effects of bilateral vs unilateral tibial nerve stimulation of percutaneously recorded spinal evoked potentials (SEP) in the lumbar and caudal thoracic area in dogs. The overall amplitude of the SEP is increased by this means. Use of this method could improve legibility of the recordings. Amplitudes of root and interneuronal components of the SEP are doubled as are cranially transmitted depolarizations. However, the amplitude of the SEP component arising from the primary afferents' depolarization was less than doubled. Latencies of the components were unaffected by bilateral stimulation. Careful observation of the latencies disclosed a 0.9-ms delay in transmission of the fastest component in the midlumbar area. This delay was consistent with results of previous cordotomy experiments, and could influence precision of conduction velocity measurement. PMID- 1510304 TI - Age-related effects on motor nerve conduction velocity in chickens. AB - Compound motor-nerve action potentials evoked by supramaximal stimulation of the proximal and distal aspects of the tibial nerve were evaluated in chickens 1 to 15 weeks old. Motor-nerve conduction velocity increased from a mean of 22.6 m/s at week 1 to a mean of 52.7 m/s at week 15. The increase in conduction velocity was greatest for the first few weeks, and reached a plateau at 10 weeks. Subcutaneous limb temperature, limb length, and proximal latency measurements also increased with age; however, distal latency measurements were not significantly influenced by age. A quadratic equation was calculated to predict mean motor-nerve conduction velocity for maturing chickens. PMID- 1510305 TI - Isolation of Mycobacterium paratuberculosis after oral inoculation in uninfected cattle. AB - Feces from cows naturally infected with Mycobacterium paratuberculosis was given to 6 uninfected heifers by orogastric intubation, to determine whether ingested organisms could be passively excreted and detected by bacteriologic culture of feces (ie, false-positive result). Heifers were paired, and each pair received a different dose of feces on days 1 and 2. Fecal samples were collected from the heifers 3 times daily. Mycobacterium paratuberculosis was detected in fecal samples of all heifers within 18 hours of being given the first dose of feces. The number of colony-forming units peaked on days 3 or 4, and organisms were no longer detected by day 7. The number of colony-forming units in fecal samples from the heifers was approximately proportional to the dose given. On days 15 and 16, the experiment was repeated with feces from a second infected cow. Results were similar to those in the first experiment. All heifers remained seronegative (agar-gel immunodiffusion test and ELISA) and had negative results to the intradermal johnin test throughout the experiment. Lymph node and intestinal tissues were obtained from all 6 heifers at slaughter on day 28. Mycobacterium paratuberculosis was not isolated from mesenteric lymph nodes from the ileocecal valve region, but was isolated from ileal mucosal samples from each heifer. PMID- 1510306 TI - Antibody response of calves to immunoaffinity-purified bovine respiratory syncytial virus VP70 after vaccination and challenge exposure. AB - Immunoaffinity-purified bovine respiratory syncytial virus (BRSV) fusion (F) protein elicited anti-BRSV-specific antibody responses in BRSV-seronegative calves. After primary vaccination, all calves seroconverted to BRSV as determined by the virus neutralization (VN) test and developed anti-F protein antibodies detectable by protein immunoblot analyses. Subsequent vaccinations induced greater than twofold increase in VN titer in 3 of 9 (33%) calves, and 1 calf became VN-negative, but still had nonneutralizing antibody detectable by protein immunoblot analysis. This calf remained seronegative after challenge exposure. Two groups of calves were vaccinated IM with immunoaffinity-purified BRSV F protein. Each dose was 2 ml containing 20 micrograms of purified F protein. Freund's adjuvants were used for all vaccinations, with Freund's complete adjuvant used for the primary vaccination and Freund's incomplete adjuvant for subsequent vaccinations. The vaccine was administered to both groups at weeks 0 and 3; the first group received a third vaccination at weeks 21. Group-1 and -2 vaccinated calves and non-vaccinated contact controls were intranasally aerosol challenge-exposed with low cell culture-passage BRSV on weeks 22 and 9, respectively. Eight of 9 vaccinated calves did not develop a humoral anamnestic response following challenge exposure, as demonstrated by VN test and protein immunoblot analyses. Calf 14 from group 1 which had a 1:2 VN antibody titer prior to vaccination, was the only calf that developed an anamnestic response.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1510307 TI - Susceptibility of dogs to infection with Ehrlichia chaffeensis, causative agent of human ehrlichiosis. AB - Ehrlichia chaffeensis, the newly recognized agent of human ehrlichiosis, is closely related to E canis, the causative agent of canine ehrlichiosis. Eight pups were inoculated IV with E chaffeensis-, or with E canis-infected DH82 cells, or organisms released from these host cells. Two additional pups served as nonexposed controls. Marked thrombocytopenia was observed in the E canis-infected pups, but not in those infected with E chaffeensis. Homologous serologic response was observed in the E chaffeensis-exposed pups by postinoculation day (PID) 14 and in the E canis-exposed pups by PID 21. Ehrlichia chaffeensis and E canis were reisolated from the respective inoculated pups on each of 8 attempts from PID 7 to 26. One E chaffeensis-exposed pup that was challenge exposed with E canis via blood transfusion, developed fever, anorexia, and thrombocytopenia, suggesting lack of cross protection against E canis. PMID- 1510308 TI - Characterization of a Salmonella choleraesuis isolate after repeated neutrophil exposure. AB - Salmonella choleraesuis strain 38 (glycerol-positive fermentation) was repeatedly exposed to porcine neutrophils in an attempt to mimic in vivo conditions of the host immune system. After phagocytosis, viable intracellular S choleraesuis were isolated and the process was repeated at least 5 times. A fifth-passage strain-38 neutrophil-adapted clone, 38PMNa-5X, was isolated, and was compared with the parent wild-type strain 38 for changes. Strain 38PMNa-5X had increased resistance to killing by hydrogen peroxide and phagocyte killing by porcine neutrophils, as measured by 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide reduction. Strain 38PMNa-5X was less invasive than the parent strain on Vero cell monolayers, and had been cured of a 50-kb plasmid. The 50-kb plasmid was marked with bacteriophage mini-Mu (kanamycin resistant) and was reinserted into strain 38PMNa-5X. Strain 38PMNa-5X was avirulent in mice, but the isolates with reinserted plasmids had intermediate resistance to neutrophil and hydrogen peroxide killing and had restored invasiveness and mouse virulence. Differences in complement sensitivity and enzymatic activity were not observed between the strains. PMID- 1510310 TI - Effects of triiodothyronine treatment on pharmacokinetic properties and metabolite formation of antipyrine in dwarf goats. AB - The influence of triiodothyronine (5 micrograms/kg of body weight, sc, q 12 h for 7 days) on antipyrine (AP, 25 mg/kg, IV) plasma elimination and urinary metabolite excretion was studied in castrated male dwarf goats. After triiodothyronine treatment, a significant increase in AP elimination was found. However, the observed changes in clearances for production of AP metabolites (nor AP, 3-hydroxymethyl-AP; 4-hydroxy-AP, and 4,4'-dihydroxy-AP) do not suggest a clear selectivity of triiodothyronine toward any of the metabolic pathways of AP. PMID- 1510309 TI - In vivo isolation of Salmonella choleraesuis from porcine neutrophils. AB - Seventy-five pigs from 4 facilities were examined for Salmonella choleraesuis by use of bacteriologic culture of feces, blood, WBC (buffy coat), mononuclear leukocytes, and neutrophils. The organism was isolated from 0 of 75 fecal samples, compared with isolation from 39 of 75 purified neutrophil preparations. Of the pigs that did not have Salmonella isolated from feces or blood, but had S choleraesuis isolated from neutrophils, 6 were further examined. These pigs from 2 groups again had culture performed at least 3 successive times to test for repeatability and to determine optimal number of neutrophils required for Salmonella isolation. These same pigs were euthanatized and necropsied. Nineteen tissue specimens from each pig were obtained for culture, but S choleraesuis was isolated only from neutrophil samples. Results indicate that neutrophils may contribute to the carrier state in pigs and should be cultured when attempting to identify S choleraesuis carrier swine. PMID- 1510311 TI - Effects of Ehrlichia phagocytophila infection on serum thyroid hormone concentrations and on antipyrine clearance and metabolite formation in dwarf goats. AB - The influence of infection with Ehrlichia phagocytophila (EP) on serum thyroid hormone concentrations and on antipyrine (25 mg/kg of body weight, IV) plasma elimination and urinary metabolite excretion was studied in castrated male dwarf goats. Mean thyroid hormone concentrations moderately decreased in EP-infected goats, with maximal decrease in total and free triiodothyronine and thyroxine serum concentrations of 56, 64, 23, and 19%, respectively. The estimated pharmacokinetic values of antipyrine (AP) in EP-infected goats were similar to those in the goats when healthy. However, glucuronidation of the AP-metabolites 3 hydroxymethyl-AP, 4,4'-dihydroxy-AP, and 4-hydroxy-AP was reduced during the febrile episode of the acute-phase response to EP infection. PMID- 1510312 TI - Analgesia and behavioral responses of dogs given oxymorphone-acepromazine and meperidine-acepromazine after methoxyflurane and halothane anesthesia. AB - This study was designed to test analgesia, duration, and cardiovascular changes induced by meperidine (MEP) and oxymorphone (OXY) following methoxyflurane (MOF) and halothane (HAL) anesthesia. Eight healthy dogs were given atropine and acepromazine, and anesthesia was induced with thiamylal and maintained with 1.5 minimal alveolar concentration of MOF or HAL for 1 hour during controlled ventilation. Eight treatments were given with each anesthetic: 3 with MEP (0.5, 1.0, and 2.0 mg/kg, IV), 3 with oxymorphone (OXY; 0.05, 0.1, and 0.2 mg/kg, IV), and 2 placebos with sterile water. Test drugs were given at the end of anesthesia when early signs of recovery were evident. Minimal threshold stimulus/response nociception was assessed by use of an inflatable soft plastic colonic balloon. Blood pressures and pulse rate were measured with a noninvasive monitor. Meperidine and OXY were found to be effective analgesics and could be reversed with naloxone. Intravenous administration of 2.0 mg of MEP/kg provided analgesia for 36 +/- 6 minutes and 39 +/- 15 minutes after MOF and HAL, respectively. In contrast, OXY was effective at all 3 doses with effects of IV administration of 0.2 mg of OXY/kg lasting 154 +/- 13 minutes and 152 +/- 12 minutes, after MOF and HAL, respectively. Analgesia could not be demonstrated after anesthesia for acepromazine, MOF, or HAL. Blood pressure was not changed by either anesthetic nor was it influenced by MEP or OXY. Pulse rate was significantly depressed by the higher doses of OXY following HAL, but was not changed by MEP following either anesthetic.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1510313 TI - Effects of lung site and fluid volume on results of bronchoalveolar lavage fluid analysis in horses. AB - Bronchoalveolar lavage (BAL) fluid was analyzed in healthy horses, using different lavage fluid volumes and lung sites. The only significant difference in the cellular composition of BAL fluid between the right and left lungs was the mast cell numbers, which were significantly higher in the left lung. Total cell count ranged from 34 to 330 cells/microliter for the right lung and 43 to 330 cells/microliter for the left lung. Percentage of neutrophils ranged from 1 to 7% in the right lung and 1 to 5% in the left lung. The small-volume (50 ml) lavage had a greater percentage of neutrophils and a lesser percentage of mast cells in the large-volume (350 ml) lavage. Statistical difference in the composition of BAL fluid recovered was not detected between the 3 sequential 100-ml lavages and a single 300-ml lavage, except that macrophages were significantly higher in the 3 sequential 100-ml lavages. Values for BAL fluid analysis in healthy horses have varied considerably and this variation is from a failure to adhere to any standard technique for volume of fluid infused. PMID- 1510314 TI - Evaluation of hemorheologic variables as implications for exercise-induced pulmonary hemorrhage in racing thoroughbreds. AB - Hematologic and rheologic changes were examined in 49 Thoroughbreds before and after competitive racing. Mean postrace values for RBC count, hemoglobin concentration, and PCV increased by 58 to 61%, whereas blood viscosity increased 2 to 3 times. Postrace echinocyte numbers were 162% greater than prerace values. Smaller, but statistically significant, changes were found for mean corpuscular hemoglobin concentration, red cell distribution width, plasma total protein concentration, total WBC count, neutrophil count, and lymphocyte count. Variables measured did not predict whether a horse was a bleeder not treated with furosemide, a bleeder treated with furosemide, or a nonbleeder. PMID- 1510315 TI - Comparison of subjective and objective test evaluations for use of Mycobacterium phlei-adsorbed serum in a dot-enzyme-linked immunosorbent assay for diagnosis of paratuberculosis in cattle. AB - Use of a dot-ELISA with serum adsorbed with Mycobacterium phlei or with nonadsorbed serum was compared. In addition, results attained using visual observation were compared with those obtained using a densitometer. Infection status of cattle was determined by results of culture of feces from a number of cattle with various degrees of exposure (low prevalence and test-negative) and disease manifestation (clinical suspect vs subclinical infection). Two paratuberculosis-negative herds, fecal culture-confirmed clinically suspect cases of paratuberculosis, and cows from 2 paratuberculosis-infected herds with diagnosis confirmed on the farm (low infection rate) were tested. Significant (P less than 0.05) increase in the dot-ELISA response was found in cattle with heavy M paratuberculosis shedding when nonadsorbed and adsorbed sera were used, compared with the response in cattle that were fecal culture-negative or were shedding M paratuberculosis at lower amounts. Paratuberculosis was diagnosed by visual determination in 29 of 44 (65.9%) of fecal culture-positive, clinically suspect cattle when nonadsorbed serum was used. Results of the visual test were negative in 85 of 93 (91.4%) of the fecal culture-negative cattle when nonadsorbed serum was used. However, when using M phlei-adsorbed serum, the sensitivity of the visual determination decreased to 34.1% (15/44), and the specificity increased to 97.8% (91/93).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1510316 TI - Comparison of intravenous and intramuscular routes of administering cosyntropin for corticotropin stimulation testing in cats. AB - Plasma cortisol and immunoreactive (IR)-ACTH responses to 125 micrograms of synthetic ACTH (cosyntropin) administered IV or IM were compared in 10 clinically normal cats. After IM administration of cosyntropin, mean plasma cortisol concentration increased significantly (P less than 0.05) within 15 minutes, reached maximal concentration at 45 minutes, and decreased to values not significantly different from baseline concentration by 2 hours. After IV administration of cosyntropin, mean plasma cortisol concentration also increased significantly (P less than 0.05) at 15 minutes, but in contrast to IM administration, the maximal cortisol response took longer (75 minutes) and cortisol concentration remained significantly (P less than 0.05) higher than baseline cortisol concentration for 4 hours. Mean peak cortisol concentration (298 nmol/L) after IV administration of cosyntropin was significantly (P less than 0.05) higher than the peak value (248 nmol/L) after IM administration. All individual peak plasma cortisol concentrations and areas under the plasma cortisol response curve were significantly (P less than 0.05) higher after IV administration of cosyntropin than after IM administration. Mean plasma IR-ACTH concentration returned to values not statistically different from baseline by 60 minutes after IM administration of cosyntropin, whereas IR-ACTH concentration still was higher than baseline concentration 6 hours after IV administration. Peak plasma IR-ACTH concentration and area under the plasma IR-ACTH response curve also were significantly (P less than 0.05) higher after IV administration of cosyntropin. Results of the study confirmed that IV administration of cosyntropin induces significantly (P less than 0.05) greater and more prolonged adrenocortical stimulation than does IM administration.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1510317 TI - Efficacy of buparvaquone as a therapeutic and clearing agent of Babesia equi of European origin in horses. AB - We evaluated the efficacy of buparvaquone in eliminating infection with Babesia equi of European origin in carrier horses and in splenectomized horses with experimentally induced acute infection. When administered at the rate of 5 mg/kg of body weight, IV, 4 times at 48-hour intervals, buparvaquone prompted rapid abatement of parasitemia. However, secondary and tertiary recrudescent parasitemias invariably returned with establishment of the carrier state. Buparvaquone, at the dosage evaluated, had transitory therapeutic efficacy against acute B equi infection in splenectomized horses, but was unable alone to clear carrier infection. PMID- 1510318 TI - Efficacy of orally administered moxidectin against naturally acquired gastrointestinal nematodes in cattle. AB - Anthelmintic efficacy of moxidectin, an experimental antiparasitic macrocyclic lactone, was evaluated in a group of 15 calves harboring naturally acquired gastrointestinal nematodes. Three groups of 5 calves each served as untreated controls (group 1) or principals that were given moxidectin PO at the rate of 0.2 mg/kg (group 2) or 0.4 mg/kg (group 3) of body weight. Equal numbers of control and treated calves were necropsied for parasite recovery on days 10 (3 control and 3 of each treatment group) and 11 (2 control and 2 of each treatment group) after treatment. Efficacies at both doses were greater than 99.8 and 99.9% against active and inhibited larvae and adults of Ostertagia spp, respectively. The overall mean efficacy of each dose was greater than 99.9%. PMID- 1510319 TI - Efficacy of a chewable formulation of ivermectin against a mixed infection of Ancylostoma braziliense and Ancylostoma tubaeforme in cats. AB - The efficacy of a beef-based, chewable formulation of ivermectin against a mixed infection of Ancylostoma braziliense and A tubaeforme was determined in cats. Ivermectin administered orally at approximately 24 micrograms/kg of body weight was 92.8% effective against adult A braziliense and 90.7% effective against adult A tubaeforme. The number of eggs per gram of feces had decreased 98.1% by 7 days after treatment. Clinical signs of hookworm disease also decreased after treatment. Location of adult parasites within the small intestine, percentage of infecting larvae that developed to the adult stage, and egg size in cats with infections of A braziliense and A tubaeforme were similar to those reported for cats with separate infections of either species. PMID- 1510320 TI - Effects of exercise stress on various immune functions in horses. AB - Chemotactic locomotion and luminol-dependent chemiluminescence of neutrophils, mitogen-induced lymphocyte blastogenesis, serum cortisol concentration, immunoglobulin quantification, and leukocyte counts were determined to evaluate the effect of a single strenuous exercise in horses. Increased serum cortisol concentration (P less than 0.01) and an increased neutrophil-to-lymphocyte ratio (P less than 0.05) indicated that horses had been stressed. The chemotactic index and peak chemiluminescence production decreased significantly (P less than 0.05 and P less than 0.01, respectively) 1 day after exercise. Mitogen-induced blastogenesis of lymphocytes and serum immunoglobulin values remained unchanged in response to exercise. Results of this study indicated that a single bout of exercise may transiently impair neutrophil antimicrobial functions and nonspecific defense mechanisms, but not specific immunity in horses. PMID- 1510321 TI - Effect of estradiol-17 beta treatment of gilts on blood mononuclear cell functions in vitro. AB - Porcine blood mononuclear cells (BMC) were exposed to prepartum concentration of estrogen in gilts before acquisition (in vivo), and their subsequent reactivity (in vitro) was explored. In a cross-over experimental designed study, 6 ovariectomized gilts were injected once with 3.75 mg of estradiol-17 beta benzoate in arachidic oil or with arachidic oil only during 2 experiments. The ability of their BMC to proliferate in response to stimulation with phytohemagglutinin, concanavalin A, and pokeweed mitrogen was assayed in cultures of blood and in cultures of purified BMC. After 2 days of mitogen stimulation, activity of accessible interleukin 2 was quantified in supernatants obtained from cultures of purified BMC and supernatants of blood cultures stimulated with pokeweed mitogen. Also, production of immunoglobulins by purified BMC in response to polyclonal stimuli was measured. Three days after treatment with estradiol, the proliferative response was suppressed in blood cultures stimulated with concanavalin A (P less than 0.05) and phytohemagglutinin (P less than 0.07). Effects of estradiol treatment were not found in any of the assays performed with purified BMC. We, therefore, assumed that in vivo exposure to estradiol can affect the function of porcine BMC; however, this was only evident when the in vitro assays were performed on blood cultures. PMID- 1510322 TI - Communication between the femoropatellar and medial and lateral femorotibial joints in horses. AB - Communications between the femoropatellar, medial femorotibial, and lateral femorotibial joints were studied, using fresh equine cadaver specimens. A total of 90 specimens from 45 horses were used. Horses were randomly assigned to 3 groups with 15 horses/group. Each group was assigned an injection site (femoropatellar joint, medial femorotibial joint, or lateral femorotibial joint), and red latex was injected into the respective location of each joint in each group. Immediately after injection, the joints were flexed and extended 100 times. The stifles were frozen in slight flexion, then cut into 1-cm sagittal sections. The communications between the femoropatellar and medial and lateral femorotibial joints were determined. None of the specimens in this study had communication between all 3 joint compartments. When the femoropatellar joint was injected, 18 of 30 joints (60%) communicated with the medial femorotibial joint, and 1 of 30 (3%) communicated with the lateral femorotibial joint. Injection of the medial femorotibial joint revealed 24 of 30 (80%) joints that communicated with the femoropatellar joint, and 1 of 30 (3%) that communicated with the lateral femorotibial joint. Injection of the lateral femorotibial joint resulted in communication with the femoropatellar joint in 1 of 30 (3%) joints. Communication did not exist between the medial and lateral femorotibial joints. PMID- 1510323 TI - Identification and categorization of the vascular patterns to muscles of the thoracic limb, thorax, and neck of dogs. AB - Vascular patterns to thoracic limbs, thorax, and neck muscles were studied in 10 dogs (20 limbs) to identify muscles most suitable for transposition in the treatment of large wounds. Gross dissection of injected specimens and angiography were used to identify vascular pedicles. Size and location of pedicles were generally consistent, and any variations would not interfere with most muscle transfers. The cutaneous trunci, latissimus dorsi, sternothyroideus, sternohyoideus, deep pectoral, anconeus, ulnaris lateralis, and ulnar head of flexor carpi ulnaris muscles were identified as suitable for transfer. The cranial trapezius, caudal omotransversarius, cleidobrachialis, and caudal sternocephalicus muscles also had potential for use. Other muscles, because of inaccessibility or unfavorable vascular pattern, were not suitable candidates for transfer. PMID- 1510324 TI - Effects of intra-articular administration of methylprednisolone acetate on normal articular cartilage and on healing of experimentally induced osteochondral defects in horses. AB - The effects of intra-articular administration of methylprednisolone acetate (MPA) on the healing of full-thickness osteochondral defects and on normal cartilage were evaluated in 8 horses. In group-1 horses (n = 4), a 1-cm-diameter, full thickness defect was created bilaterally in the articular cartilage on the dorsal distal surface of the radial carpal bone. Cartilage defects were not created in group-2 horses (n = 4). One middle carpal joint was randomly selected in each horse (groups 1 and 2), and treated with an intra-articular injection of 100 mg of MPA, once a week for 4 treatments. Injections began 1 week after surgery in group-1 horses. The contralateral middle carpal joint received intra-articular injections of an equivalent volume of 0.9% sodium chloride solution (SCS), and served as a control. Horses were evaluated for 16 weeks, then were euthanatized, and the middle carpal joints were examined and photographed. Synovial and articular cartilage specimens were obtained for histologic and histochemical evaluation. Gross morphometric evaluation of the healing defects in group-1 horses revealed that 48.6% of the defect in control joints and 0% of the defect in MPA-treated joints was resurfaced with a smooth, white tissue, histologically confirmed as fibrocartilage. This replacement tissue was a firmly attached fibrocartilage in control joints and a thin fibrous tissue in MPA-treated joints. The articular cartilage in joints treated with MPA had morphologic changes, including chondrocyte cluster formation, loss of palisading architecture, and cellular necrosis in both groups of horses.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1510325 TI - Evaluation of sodium carboxymethylcellulose for prevention of adhesions after uterine trauma in ewes. AB - Efficacy of a 1% solution of sodium carboxymethylcellulose (CMC) infused into the peritoneal cavity of ewes was evaluated for prevention of intraperitoneal adhesions resulting from surgery of the reproductive tract. Six ewes were assigned to each of 4 groups. Group-1 ewes were controls that underwent ventral midline celiotomy and exploration of the abdominal viscera. Group-2 ewes were treated similarly to group-1 ewes, except that a 1% solution of CMC (14 ml/kg of body weight) was infused into the peritoneal cavity. This group was studied to determine whether CMC would cause changes in the peritoneal cavity. Group-3 comprised ewes representing a uterine trauma model. Ewes underwent abdominal exploration, but in addition had a standard embryo collection technique performed on 1 uterine horn and hysterotomy performed on the opposite uterine horn. Group-4 ewes were treated like group-3 ewes, except that, similar to treatment of group-2 ewes, CMC was infused into the peritoneal cavity. All ewes were euthanatized and necropsied 12 to 14 days after surgery. Abdominal adhesions were evaluated, and an adhesion severity score was assigned to each ewe on the basis of number and severity of the adhesions. Ewes of all groups had abdominal adhesions. Significantly (P less than 0.05) lower adhesion score was observed in ewes given CMC (groups 2 and 4) than in the adhesion model (group 3). Significant difference was not observed in adhesion score when groups 1, 2, or 4 were compared. Though not statistically significant, fewer adhesions were observed in ewes of groups 2 and 4 than in group-1 ewes. PMID- 1510326 TI - Osmotic stress in red blood cells from beagles with hemolytic anemia. AB - Red blood cell populations separated by density centrifugation were compared in a dynamic assay of osmotic stress. Red blood cells from Beagles genotypically normal and nonanemic (nonaffected), Beagles with inherited hemolytic anemia (anemic), and Beagles presumed to be carriers of the anemia trait (trait carriers) were examined for rate and extent of swelling after exposure to the ionophore A23187 in a medium containing calcium and potassium chloride. Comparisons were made between RBC populations separated on the basis of density. Significant differences were observed in the rates of cell swelling in RBC populations separated by density between nonaffected and anemic Beagles. The response of RBC from Beagles presumed to carry the anemia trait was similar to that of RBC from nonaffected dogs. One phenotypic expression of this inherited abnormality of RBC in Beagles was an accelerated rate of RBC swelling under osmotic stress, and this swelling response diminished with increasing RBC density. PMID- 1510327 TI - Detection of African swine fever viral antigens in paraffin-embedded tissues by use of immunohistologic methods and polyclonal antibodies. AB - Tissues obtained from pigs inoculated with African swine fever virus (ASFV), fixed by vascular perfusion using glutaraldehyde, and embedded in paraffin or araldite were used for an immunohistologic electron microscopic study. To detect ASFV antigens, 4 methods were used on paraffin sections with or without pretreatment of the tissues. Use of biotinylated anti-ASFV antiserum combined with avidin-biotin complex and peroxidase proved to be the most suitable method, and antigen was detected in tissues infected with 2 ASF viruses of different virulence. Use of the glutaraldehyde fixation method should ensure optimal morphologic (structural and ultrastructural) data while allowing an immunohistologic study, and add to knowledge of the pathogenesis of ASF. PMID- 1510328 TI - Psychological testing and assessment in the 21st century. AB - As spin-offs of the current revolution in the cognitive and neurosciences, clinical neuropsychologists in the 21st century will be using biological tests of intelligence and cognition that record individual differences in brain functions at the neuromolecular, neurophysiologic, and neurochemical levels. Assessment of patients will focus more on better use of still intact functions, as well as rehabilitating or bypassing impaired functions, than on diagnosis, as is the focus today. Better developed successors to today's scales for assessing personal competency and adaptive behavior, as well as overall quality of life, also will be in wide use in clinical settings. With more normal individuals, use of new generations of paper-and-pencil inventories, as well as biological measures for assessing differences in interests, attitudes, personality styles, and predispositions, is predicted. PMID- 1510329 TI - Social psychological contributions to the decade of the brain. Doctrine of multilevel analysis. AB - The 1990s were declared by Congress to be the "decade of the brain." This declaration is important to all psychologists, not only neuroscientists, because with this declaration come expectations of the cognitive and behavioral sciences generally and because the brain does not exist in isolation but rather is a fundamental component of developing and aging individuals who themselves are mere actors in the larger theater of life. This article examines the importance of a multilevel, integrative approach to the study of mental and behavioral phenomena in the decade of the brain, reviews how this approach highlights the synergistic relationship between theoretical and clinically relevant research, and illustrates how this approach can foster the transition from microtheories to general psychological theories. PMID- 1510330 TI - Injury control. A promising field for psychologists. AB - Injury is the fourth leading cause of death for all Americans and the most frequent cause of death for those from age 1 to 45. Moreover, injury is associated with higher treatment costs and with greater lost life-years than the other three leading causes of death. Traffic accidents are the leading cause of severe brain injury, including most paraplegic and quadriplegic cases. Because injury control is essentially psychological, there are many opportunities for psychologists to contribute, both to scientific research on the causes of injury and to clinical interventions for injury control. PMID- 1510331 TI - The federal role in injury control. AB - Early federal injury control programs in the 1960s and 1970s were centered first in the Division of Accident Prevention (Public Health Service) and subsequently in the National Highway Traffic Safety Administration (Department of Transportation) and the Consumer Product Safety Commission. The Centers for Disease Control (CDC) in the early 1970s also began to investigate injuries, particularly in the home and recreational environment. The field expanded in the 1970s and 1980s to include injuries that occur in many settings and both intentional injuries (violence) and unintentional injuries. After a 1985 report, Injury in America, CDC was chosen to be the national coordinating agency because of its mission of prevention. The current program also includes acute care, rehabilitation, and biomechanics. PMID- 1510332 TI - Injury control. What psychologists can contribute. AB - Psychologists are inadequately represented in the injury control field, despite the size of the problem and the importance of behavioral factors in injury. Using motor vehicle injuries as an example, this article discusses modern injury control principles and the role psychologists can play in injury reduction. PMID- 1510333 TI - Complacency, misdirection, and effective prevention of children's injuries. AB - Injuries are the leading killer of children in the United States, yet most parents, communities, and legislatures remain uncommitted to effective injury prevention. Possible reasons for this complacency are described, and effective methods, likely targets, and useful tactics for prevention are reviewed. The greatest challenges to injury preventionists are to persuade those who remain uninformed concerning the importance of injury prevention, to redirect those efforts currently devoted to ineffective interventions, to continue to evaluate and implement effective preventive interventions, and to search for improved prevention strategies. PMID- 1510334 TI - Primary prevention of catastrophic injury. AB - Motor vehicle crashes are a leading cause of injury and death until age 45. Efforts to prevent these injuries have largely followed the dictates of the public health movement focusing on interventions for entire communities or regulatory statutes. Individual interventions, more congruent with traditional psychological approaches, have been rare. This article argues that a blending of these two approaches is warranted. Evaluation of prevention programs should focus on multiple levels including the individual, the community, and regulatory processes. Identification of subgroups of adolescents and young adults with unique psychological and behavioral dispositions regarding injury must be paired with realistic interventions of adequate duration. PMID- 1510335 TI - Early childhood intervention. A promising preventative for juvenile delinquency. AB - Programs to reduce or prevent juvenile delinquency have been generally unsuccessful. Apparently the risk factors that make a child prone to delinquency are based in too many systems--including the individual, the family, and community networks--to make isolated treatment methods effective. Surprisingly, longitudinal studies of some early childhood intervention programs suggest they may help to reduce future delinquency. These programs take an ecological approach to enhancing child development by attempting to promote overall social competence in the many systems impacting on children. Not engaging in criminal acts is one indicator of competence that is related to others, such as being successful in school and in personal relationships. Evaluators must gather more data to confirm this unanticipated benefit of comprehensive interventions. PMID- 1510336 TI - Thiacetarsamide (adulticide) versus melarsomine (RM 340) developed as macrofilaricide (adulticide and larvicide) to cure canine heartworm infection in dogs. AB - To implement a new macrofilaricide, treatment of heartworm infection or disease in dogs was checked in all the clinical situations ie from subclinical to severe disease. After preliminary toxicity and efficacy models on experimentally infected dogs, in addition, to the reference posology (2.5 mg of melarsomine (RM 340)/kg twice, 24 h apart by deep IM injection) a more practical program for vet practitioners was suggested (2.2 mg/kg twice, 3 h apart) using modelization of the pharmacokinetic data. The two treatments were equivalent as shown on models with experimental infection of dogs, critical tests on naturally infected dogs and clinical trials in veterinary practice. We advise using specific and well adapted therapeutic programs for each of the clinical classes (class 1: subclinical, class 2: moderate, class 3: severe). The safety margin is respectively x 3 or x 2.5 in contrast with thiacetarsamide which, being hepatotoxic, has no safety margin, and sometimes is nephrotoxic at the recommended dose. RM 340 is fully effective on D immitis adults (even on young ones of 7 months old) and L5 immatures (4 months old) when thiacetarsamide is poorly effective on 7 months or ineffective on 4-month-old parasites. Clinical trials in veterinary practice showed that the programs are well adapted to many clinical situations. The product is effective, relatively safe and easy to handle by IM injection. Preliminary results show its possible use as tactical treatment (2.2 mg/kg twice, 3 h apart) twice a year in mid August and December-January to prevent heartworm disease. PMID- 1510337 TI - [Enteropathogenic Escherichia coli from the rabbit]. AB - Intestinal pathology is the main cause of morbidity and mortality in breeding colonies of commercial rabbits. Among pathogens, some strains of Escherichia coli are widely involved in enteric infections. In France, pathogenic E coli belonging to the 0103 serogroup has been isolated in 30-40% of weanling rabbits with diarrhea. Given these conditions, it was of interest to review the different groups of diarrheogenic E coli and their plasmid-encoded virulence properties, especially adhesion and secretion of enterotoxins or cytotoxins. We attempted to investigate the E coli responsible for diarrhea in the rabbit, particularly those belonging to the 015 and 0103 serogroups. Like E coli 015, the pathogenic strains of the 0103 serogroup adhere to intestinal cells and induce effacement of microvilli with pedestal formation. Thus, these strains which are also non invasive and do not synthetize classical LT or ST enterotoxins, could be considered as enteropathogenic E coli (EPEC) or enterohemorrhagic E coli (EHEC). In fact, E coli 0103 is often associated with severe hemorrhagic diarrhea. Enteropathogenic E coli 0103 could therefore be a good model for studying intestinal pathology due to EPEC or EHEC in the young rabbit or in other animals and man. PMID- 1510338 TI - [Histomorphometric study of the superficial pectoral muscle of the turkey. Relationship with the meat discoloration syndrome]. AB - Scallop discoloration affects about 30% of turkey carcasses, causing important economic losses. Histological and histomorphometric analyses of the superficial pectoral muscle were performed in order to show distinctive aspects of discolored scallops and predictive criteria for the phenomenon. Pectoral muscles of live male turkeys were biopsied 8 d before slaughter. Twenty four h after slaughtering, the same animals were classified into 2 distinctive classes by reflectometry (pale and dark muscles) and muscle samples were collected in each group. Superficial pectoral muscle was totally composed of type IIB, fast switch and glycolytic fibers. Pale and dark muscles exhibited no significant differences 8 d before slaughtering, but glycogen level was higher in pale muscles 24 h after slaughtering. These results do not support the current hypothesis of accelerated glycolysis and low ultimate pH to explain the meat discoloration syndrome in turkeys. PMID- 1510339 TI - [Muscular lesions and enzymatic activities in fighting bulls]. AB - The aim of this study was to determine whether some muscular pathology existed in fighting bulls, in relation or not to the weakness shown in these animals during the bullfight (corrida for males and tienta for females). Creatinine kinase (CK), lactate dehydrogenase (LDH) and aspartate transaminase (AST) serum enzyme activities were increased after the corrida or the tienta. Most of the fighting bulls (78%) had some histological lesions in the skeletal or cardiac muscle, with predominance of chronic lesions. Clinical signs of these chronic lesions could only be seen after some trigger-effect, such as physical, exercise or stress, as shown after the corrida or tienta. PMID- 1510340 TI - [Infection by avian chlamydiosis in breeding pigeons in New Caledonia]. AB - An epidemiological survey on avian chlamydiosis, carried out by serological probing in 8 pigeon breeders representative of New Caledonian livestock, combined with bacteriological research on pigeon organs and droppings was set up in New Caledonia in order to determine the prevalence rate of this infection and to adapt sanitary regulations concerning pigeon imports. All sera collected (230) were analysed by complement fixation test (CFT). The organs were diluted in sucrose solution, then stored frozen (-70 degrees C), until inoculation of the yolk-sac of 3 6-8-day-old embryonated eggs (2 blind passages). Yolk-sac smears stained according to the Gimenez method were made in order to detect intracellular chlamydial organisms. Seventeen sera out of 230 were found to be positive, ie 7.4% of the test sample (confidence interval to 95% = 4.0 to 10.8%). The carrier pigeons were significantly more infected (17.8%) than pigeons of other breeds in New Caledonia. These results resulted in the sanitary authorities easing restrictions on imports of seropositive pigeons by imposing a 45-day compulsory quarantine with daily administration of chlortetracycline at the rate of 150 mg per 1 of drinking water. PMID- 1510341 TI - [Virulence factors and phenotypes of sixty-one strains of Escherichia coli of bovine origin, producing cytotoxic necrotising toxin type 1 (CNF 1)]. AB - Virulence factors and phenotypes of 61 strains CNF1+ were investigated. Eighty nine percent of the strains produced an aerobactin and were resistant to the bactericidal activity of sheep serum, both of which are properties of septicemic strains of E coli. None of the strains reacted either with DNA probes corresponding to the enterotoxins STaP, STb, LT-I and LT-IIa, or to the verotoxins VT-I and VT-II. None produced the adhesins K99, Att25 (FY or F17) and Att111. The great majority (93.4%) of the CNF1+E coli possessed both properties. These properties allow CNF1+ to be distinguished from CNF-E coli. PMID- 1510342 TI - A spatial analysis of 100 surnames in England and Wales. AB - Spatial patterns are described and analysed for the 84 most common surnames in England and Wales, as well as 16 others selected for various reasons. At least three-quarters of the surname frequencies show spatial structure and are heterogeneous over the area of study. While they do not exhibit clines extending over the entire area of study, they do divide into four characteristics patterns. Spatial autocorrelation, while significant, is relatively low; similarity in surname frequency does not extend much beyond 100 km. Correlograms could be clustered to yield groups of surfaces denoting partial clines, isolation by distance, and differentiation at far distances. A method for detecting zones of rapid change found 21 such zones, mostly near the periphery of the study area. These boundaries do not indicate barriers to gene flow, but appear to be patterns brought about by historical factors. There are diffusion patterns between areas that differ greatly in surname composition, such as Wales and central England. There is little evidence of long-distance movements involving several surnames. At least three characteristic migration patterns, east-west and north-south diffusion and local dispersal, were found. PMID- 1510343 TI - Serum lipids and blood pressure in relation to age and sexual maturity. AB - This study was designed to examine serum lipid profile and blood pressure in relation to age and sexual maturity. Written informed consent to participate was obtained from 42% of the eligible population of two Devon communities. The blood pressure of 343 boys and 336 girls, aged 11-16 years, was recorded and sufficient blood for analysis was obtained from 320 boys and 301 girls. Of these, sexual maturity of 221 boys and 209 girls was visually assessed using the indices developed by Tanner. In girls there was a significant (p less than 0.05) correlation between age and serum triglyceride level (r = 0.16) and in boys both serum cholesterol and HDL-cholesterol were significantly (p less than 0.01) and negatively correlated with age (r = -0.25 and -0.18 respectively). Girls had significantly higher (p less than 0.05) levels of HDL-cholesterol than boys but neither sex demonstrated significant changes (p greater than 0.05) in serum lipids or lipoproteins with sexual maturity. No significant differences (p greater than 0.05) were detected between the mean diastolic blood pressures of boys and girls but older boys had significantly higher (p less than 0.05) systolic blood pressures than similarly aged girls. Age was positively and significantly correlated (p less than 0.01) with blood pressure in both boys (systolic, r = 0.49; diastolic, r = 0.30) and girls (systolic, r = 0.28; diastolic, r = 0.29). More mature children were demonstrated to have both higher systolic and diastolic blood pressures than less mature children (p less than 0.05) but when allowance was made for school year group through analysis of co variance the relationship for diastolic blood pressure in boys no longer remained significant. Blood pressures observed in this study do not raise general cause for concern but the data indicate that unfavourable serum lipid and lipoprotein profiles are common. PMID- 1510344 TI - Genetic relationships of the populations in eastern India. AB - The genetic relationships for four sets of populations in eastern India have been studied by using gene frequency data available in the literature. The Caucasoid populations in Assam and West Bengal are genetically close but different from the Mongoloid populations in the neighbourhood. The genetic distance analysis shows that the Mongoloid populations in Assam and West Bengal cluster according to their states of residence, indicating a correlation between genetic and geographical distances. PMID- 1510345 TI - The menarcheal age of Chinese girls. AB - The menarcheal age of Chinese girls was analysed based on a national survey in 1985. A total of 162,902 girls, aged 7-22 years, of Han nationality and 34,232 girls, aged 7-18, of 27 minority nationalities were sampled. Data were further subdivided into urban and rural areas. It was found that the curves of menstruating percentage in each of the subgroup were in long sigmoid shapes. The menstruating rate (MR) of Han girls was higher than that of the minority girls in almost every age group. The median menarcheal age (MMA) of Han girls was significantly lower than that of the minority girls. In Han nationality the urban girls showed higher MR and lower MMA than the rural girls. The influence of hereditary, cultural and economical factors on menarcheal age in Chinese girls is discussed. The data of this study were also compared with research reports from other world literature. PMID- 1510346 TI - Fluctuating odontometric asymmetry and maternal alcohol consumption. AB - Fluctuating asymmetry was evaluated in the dental arcades of 112 children (60 male, 52 female) of alcoholic mothers. Only individuals who showed no signs of the fetal alcohol syndrome were included. When these results were compared with those of a control group of 120 normal children, the former group was found to be significantly more asymmetric. The present study showed that canines were the least asymmetric whilst lateral incisors showed the greatest levels of asymmetry. It is suggested that the elevated levels of fluctuating odontometric asymmetry in children of alcoholic mothers may be ascribed to prenatal stress, especially during the soft tissue stage of odontogenesis. PMID- 1510347 TI - Normalizing transformations for growth standards. AB - Age-specific distributions of growth measurements, either distances or velocities, can be normalized in various ways. This paper studies the polynomial method of Healy, Rasbash and Yang (1988), Cole's (1988) power transformation and the logarithmic transformation with adjustable start. The methods are used to fit the centiles for boys' weight and for boys' height velocity from Tanner, Whitehouse and Takaishi (1966). The power and logarithmic transformations behave very similarly; the polynomial method gives less satisfactory results. The first two methods differ, however, at extreme low centiles for weight, and both give rise to problems with height velocity near adulthood. PMID- 1510348 TI - Dietary cholesterol fails to stimulate acylcoenzyme A: cholesterol acyltransferase activity in the liver of hamsters with a spontaneous high level of cholesterol. AB - The effect of exogenous cholesterol on acylcoenzyme A:cholesterol acyltransferase (ACAT) was investigated in conventional golden hamsters (NH) and in FEC hamsters characterized by a high level of cholesterol esters in the liver. ACAT activity was determined in liver microsomal fractions obtained from control animals, in animals fed 0.1% cholesterol diet or in microsomes preincubated with exogenous cholesterol. NH responded to cholesterol feeding by increasing the rate of cholesterol esterification in the liver, and exposure of the NH microsomes to media containing cholesterol stimulated ACAT activity. By comparison, whatever the conditions, cholesterol failed to alter the rate of cholesterol esterification in FEC hamsters. This finding raises several questions about cholesterol metabolism in the liver of these animals that does not fit into the well-established schemes of hepatic cholesterol metabolism. PMID- 1510349 TI - Intestinal epithelial cell surface glycosylation in mice. 1. Effect of low protein diet. AB - Mice fed on an 8% protein (low-protein; LP) diet for 21 days exhibited a significant (p less than 0.001) decrease in their body weights compared with the pair-fed controls (18% protein). Brush border enzyme analysis revealed a 56% increase in sucrase activity and a significant decrease in alkaline phosphatase (p less than 0.05), beta-D-glucosidase (p less than 0.001) and beta-D galactosidase (p less than 0.05) activities in protein-deficient mice. Lactase activity was unaltered in these conditions. Hexose and hexosamine contents of the brush border membranes (BBM) decreased considerably as a result of the LP diet. Protein deprivation significantly enhanced (p less than 0.01) brush border sialic acid and reduced (p less than 0.05) fucose content compared to the controls. The binding of 125I-labelled wheat germ agglutinin and Ulex europaeus agglutinin I to BBM was in agreement with the data on sialic acid and fucose levels of the membranes. The binding of peanut agglutinin to BBM was 38% higher in LP-diet-fed animals. The incorporation of [14C]mannose and [14C]glucosamine into BBM was markedly reduced (25%), while that of [3H]fucose was apparently unaffected. These results suggest that the feeding of an LP diet to mice results in marked alterations in the intestinal epithelial cell surface glycosylation. PMID- 1510350 TI - Soybean protein-dependent changes in triacylglycerol synthesis and concentration of diacylglycerol in the liver microsomes of fasted-refed rats. AB - Effects of soybean protein, casein and whole egg protein on various indices for lipid biosynthesis in the liver were compared in fasted-refed rats. Soybean protein compared to casein and whole egg protein significantly reduced activities of glucose 6-phosphate dehydrogenase and fatty acid synthetase. The protein source also slightly reduced the activity of the malic enzyme. Soybean protein compared to other proteins not only reduced the microsomal triacylglycerol but also phosphatidylcholine syntheses when the activities were measured with endogenous diacylglycerol substrate. The protein-dependent changes disappeared, if artificial dispersion of dioleoylglycerol was employed as a substrate. The concentrations of microsomal diacylglycerol and triacylglycerol in whole liver in rats fed soybean protein were lower than those fed other proteins. When the diets containing soybean protein and casein were supplemented with DL-methionine (0.5 and 0.3%, respectively) to meet the nutritional requirement of the animals, soybean protein-dependent reductions in these indices for lipid biosynthesis were still detectable but considerably attenuated. Thus, it is plausible that a soybean protein-dependent decrease in fatty acid synthesis reduced the availability of microsomal diacylglycerol substrate for triacylglycerol synthesis and in turn modified hepatic triacylglycerol concentration. The dietary availability of sulfur amino acids may, at least in part, be responsible for the consequence observed in the present study. PMID- 1510351 TI - Malnutrition in geriatric patients: diagnostic and prognostic significance of nutritional parameters. AB - Nutritional status was assessed in 300 geriatric patients aged 75 years or more using clinical, anthropometric, biochemical and immunologic methods. Relations between different assessment methods and their prognostic significance with regard to 18-month mortality were examined. For biochemical variables 10% (prealbumin, vitamin B6) to 37% (vitamins A and C) were below conventional limits. In 44% of the patients lymphocytes were diminished. 44% were anergic. Judgement of nutritional status by clinical impression resulted in 22% being deemed undernourished. Clinical diagnosis of undernutrition was associated with low anthropometric measurements (p less than 0.05 for all parameters) and a high prevalence of low biochemical values (p less than 0.05 for albumin, prealbumin, transferrin, vitamin A, vitamin B1). The mean values of all anthropometric variables, plasma proteins, vitamins A and C were significantly lower in patients who died within the following 18 months compared to survivors. The greatest prognostic significance was related to the clinical diagnosis of malnutrition. We conclude that clinical assessment is useful for the evaluation of nutritional status in geriatric patients and the best of numerous nutritional parameters to estimate risk of long-term mortality. PMID- 1510352 TI - New magnetic resonance techniques for evaluating cerebrovascular disease. AB - Magnetic resonance (MR) imaging of acute stroke has made important contributions to diagnosis. Several novel MR technologies, now in preclinical and clinical development, will contribute to stroke diagnosis and perhaps help to guide therapy. MR angiography is the most clinically advanced new MR technology and offers the clinician a method to image noninvasively the extra- and intracranial vasculature. Diffusion-weighted MR imaging can demonstrate ischemic lesions quantitatively within minutes of onset in experimental stroke models, and human application is proceeding. Perfusion MR studies can reveal the presence or absence of cerebral perfusion in specific arterial territories. MR spectroscopy can assess tissue metabolites in vivo and reveal changes in these metabolites associated with ischemic injury. The combination of these new MR techniques should provide a plethora of information about the extent of ischemic lesions, associated vascular and perfusion deficits, and metabolic consequences. This information will afford the clinician the opportunity to assess and subtype ischemic stroke patients more rapidly and could be used to monitor therapeutic responses. PMID- 1510353 TI - The effect of 4-aminopyridine on clinical signs in multiple sclerosis: a randomized, placebo-controlled, double-blind, cross-over study. AB - To find out whether treatment with 4-aminopyridine is beneficial in multiple sclerosis (MS), 70 patients with definite MS entered into a randomized, double blind, placebo-controlled, cross-over trial in which they were treated with 4 aminopyridine and placebo for 12 weeks each (maximum dose, 0.5 mg/kg of body weight). The estimated effect of the treatment as measured with the Kurtzke expanded disability status scale, which was the main evaluation parameter, was 0.28 point (p = 0.001). A significant decrease in the scale score (1.0 point or more) was encountered in 10 patients (16.4%) during oral treatment with 4 aminopyridine whereas it was not seen during placebo treatment (p less than 0.05). A significant subjective improvement (defined as an improvement that significantly affected the activities of normal daily life) was indicated by 18 patients (29.5%) during 4-aminopyridine treatment and by 1 patient (1.6%) during placebo treatment (p less than 0.05). Significant improvements related to 4 aminopyridine occurred in a number of neurophysiological parameters. No serious side effects were encountered. However, subjective side effects such as paresthesias, dizziness, and light-headedness were frequently reported during 4 aminopyridine treatment. Analysis of subgroups revealed that there was no difference in efficacy between those patients randomized to receive 4 aminopyridine and then placebo and those randomized to receive placebo and then 4 aminopyridine or between patients with and those without subjective side effects. Especially patients with temperature-sensitive symptoms and patients characterized by having a longer duration of the disease and being in a progressive phase of the disease were likely to show clear clinical benefit. PMID- 1510354 TI - Computer model of ethosuximide's effect on a thalamic neuron. AB - Ethosuximide appears to have a specific effect on the low-threshold calcium current in thalamic cells. This may be related to its efficacy in the treatment of absence epilepsy. We used a computer model of an individual thalamocortical neuron to better understand the alteration in the low-threshold calcium current under voltage clamp and to predict response to current injection in the presence of ethosuximide. The full model included nine voltage-sensitive ionic channels and a realistic dendritic morphology. The model reproduced the two major responses seen in tissue slices: repetitive spiking with depolarization and the low-threshold calcium spike elicited on release from hyperpolarization. The alteration in low-threshold calcium current with ethosuximide can be explained by a 10-mV depolarizing shift in the steady-state activation curve for this channel with a 10% reduction in maximum channel permeability. Simulations of current injection showed that ethosuximide diminished the low-threshold calcium spike while leaving the tonic firing pattern unaffected. Our results support the hypothesis that ethosuximide's effects on low-threshold calcium current might selectively alter the dynamics of slow bursting in thalamic cells. PMID- 1510355 TI - Impaired mesial frontal and putamen activation in Parkinson's disease: a positron emission tomography study. AB - Selection of movement in normal subjects has been shown to involve the premotor, supplementary motor, anterior cingulate, posterior parietal, and dorsolateral prefrontal areas. In Parkinson's disease (PD), the primary pathological change is degeneration of the nigrostriatal dopaminergic projections, and this is associated with difficulty in initiating actions. We wished to investigate the effect of the nigral abnormality in PD on cortical activation during movement. Using C15O2 and positron emission tomography (PET), we studied regional cerebral blood flow in 6 patients with PD and 6 control subjects while they performed motor tasks. Subjects were scanned while at rest, while repeatedly moving a joystick forward, and while freely choosing which of four possible directions to move the joystick. Significant increases in regional cerebral blood flow were determined with covariance analysis. In normal subjects, compared to the rest condition, the free-choice task activated the left primary sensorimotor cortex, left premotor cortex, left putamen, right dorsolateral prefrontal cortex and supplementary motor area, anterior cingulate area, and parietal association areas bilaterally. In the patients with PD, for the free-choice task, compared with the rest condition, there was significant activation in the left sensorimotor and premotor cortices but there was impaired activation of the contralateral putamen, the anterior cingulate, supplementary motor area, and dorsolateral prefrontal cortex. Impaired activation of the medial frontal areas may account for the difficulties PD patients have in initiating movements. PMID- 1510356 TI - Paramedian thalamopeduncular infarction: clinical syndromes and magnetic resonance imaging. AB - We prospectively examined 11 patients with magnetic resonance imaging-documented infarction in the paramedian thalamopeduncular region, which is supplied by the superior mesencephalic and posterior thalamosubthalamic arteries. Variations in the size and rostral-caudal extent of infarction correlated with the following three clinical patterns: (1) With unilateral paramedian mesencephalic infarction, an ipsilateral third nerve paresis was accompanied by mild contralateral hemiparesis or hemiataxia. Contralateral ptosis and impaired upgaze were observed in two patients; one of them showed additional damage to the posterior commissure. (2) With bilateral infarction in the thalamopeduncular junction, involving the mesencephalic reticular formation, supranuclear vertical gaze defects were accompanied by impaired consciousness or memory, and mild aphasia in some patients. Persistent amnesia was observed only when the dominant anterior nucleus or mamillothalamic tract was damaged. (3) With larger thalamopeduncular infarcts, partial or complete third nerve paresis was combined with supranuclear gaze disturbance and delayed contralateral tremor. An unusual gaze disorder, a variant of the vertical "one-and-a-half syndrome," occurred with a small strategically placed lesion at the thalamopeduncular junction, best explained by selective damage to supranuclear pathways or partial nuclear involvement. The primary cause of these infarctions was embolism to the basilar apex or local atheroma at the origin of the posterior cerebral artery. PMID- 1510357 TI - Spectral analysis of the rapid eye movement sleep electroencephalogram in right and left temporal regions: a biological marker of Alzheimer's disease. AB - Spectral analysis of electroencephalograms (EEGs) for both wakefulness and rapid eye movement (REM) sleep was performed over the temporal regions in 8 patients with mild to moderate Alzheimer's disease and in 8 age-matched control subjects. EEG slowing in Alzheimer patients was found to be much more prominent during REM sleep than during wakefulness. In addition, asymmetry on the awake EEG of Alzheimer patients was found to be even more prominent than on the REM sleep EEG. When EEG values of the most impaired hemisphere during REM sleep were examined, no overlap was found between the two groups either for the ratio of slow to fast frequencies or for percent power of each of the frequency bands. This was not the case for the awake EEG. These results suggest that diagnostically meaningful cutoff values for discriminating patients with mild to moderate Alzheimer's disease from age-matched control subjects can be derived from the REM sleep EEG of the temporal lobe. PMID- 1510358 TI - Hypodensity of the cerebral white matter in patients with transient ischemic attack or minor stroke: influence on the rate of subsequent stroke. Dutch TIA Trial Study Group. AB - In a prospective study of 3,017 patients with transient ischemic attack or minor ischemic stroke from the Dutch Transient Ischemic Attack Trial, the presence or absence of diffuse hypodensity of the white matter on a baseline computed tomography (CT) scan of the brain was related to the occurrence of subsequent stroke. On entry, 337 patients were judged to have diffuse hypodensity of the white matter on CT; they were older (71.4 +/- 7.4 years versus 64.4 +/- 9.9 years), more often had hypertension (50% versus 41%), and more often had lacunar infarcts on CT scan (40% versus 26%) than did patients with normal white matter. Strokes, fatal or nonfatal, occurred in 51 (15%) of the patients with diffuse hypodensity of the cerebral white matter, compared to 217 (8%) in the group with normal white matter (crude hazard ratio, 2.0; 95% confidence interval, 1.4-2.7). After adjustment for age and other relevant entry variables, the hazard ratio was 1.6 (95% confidence interval, 1.2-2.2). In patients younger than 70 years the crude hazard ratio was 2.7 (95% confidence interval, 1.7-4.2). The distribution between the main subtypes of stroke was similar for patients with and those without diffuse hypodensity of the cerebral white matter: Intracerebral hemorrhage occurred in 6 and 9%, cortical infarction in 47 and 45%, and lacunar infarction in 34 and 29%, respectively. We conclude that hypodensity of the cerebral white matter in patients with transient ischemic attack or minor stroke is associated with an extra risk of future stroke, from large as well as from small vessels, and particularly in patients under 70 years old; this increase of risk is independent of other risk factors for stroke. PMID- 1510359 TI - Interferon-gamma potentiates antibody-mediated demyelination in vivo. AB - The pathogenetic events leading to demyelination in experimental allergic encephalomyelitis and in human multiple sclerosis are still unclear. The involvement of anti-myelin antibodies and activated macrophages as effector cells has been postulated. We investigated the synergistic action of the monoclonal antibody 8-18C5 against myelin/oligodendrocyte glycoprotein and recombinant interferon-gamma on demyelination after simultaneous injection into the subarachnoid space of Sprague-Dawley rats. After combined injection of anti myelin/oligodendrocyte glycoprotein antibody and interferon-gamma, electrophysiological and morphological evidence for demyelination was found. Cervical somatosensory evoked potentials and cervical short-latency somatosensory evoked potentials were significantly delayed, and the demyelinated area in the spinal cord was significantly enlarged when compared to control rats injected with either compound alone. Injection of either an irrelevant antibody and interferon-gamma or of peritoneal macrophages without anti-myelin/oligodendrocyte glycoprotein antibody and interferon-gamma did not induce demyelination. Our data suggest that the deleterious effect of interferon-gamma on multiple sclerosis may be not only due to its effect on antigen presentation but also due to potentiation of demyelination. PMID- 1510360 TI - The first decade of molecular genetics in neurology: changing clinical thought and practice. AB - Molecular genetics has had a powerful impact on clinical neurology. Definitions of disease are changing from clinical criteria to DNA analysis, resolving questions about the nature of clinically similar but not identical diseases. Genetic counseling is more reliable. Concepts of mendelian inheritance are being tested and new forms of mutation have been discovered to explain anticipation. Nonmendelian forms of inheritance have emerged; concepts of pathogenesis are on a more secure footing; and novel treatments are being explored. PMID- 1510361 TI - Alzheimer's disease and hereditary cerebral hemorrhage with amyloidosis-Dutch type share a decrease in cerebrospinal fluid levels of amyloid beta-protein precursor. AB - The amyloid beta-protein is a 39-42 amino acid peptide that is deposited in senile plaques and in cerebral vessel walls in individuals with Alzheimer's disease, Down's syndrome, hereditary cerebral hemorrhage with amyloidosis-Dutch type (HCHWA-D), and, to a much lesser extent, normal aging. It is derived from abnormal proteolytic processing of its parent protein, the amyloid beta-protein precursor. Here we show that individuals with the HCHWA-D mutation and clinically manifesting the disease have markedly decreased cerebrospinal fluid levels of soluble amyloid beta-protein precursor (0.7 +/- 0.4 micrograms/ml) compared with age-matched normal subjects (3.0 +/- 0.2 micrograms/ml) as determined by quantitative immunoblotting and enzyme-linked immunosorbent assays. Similarly, age-matched patients diagnosed with probable Alzheimer's disease also have decreased cerebrospinal fluid levels of soluble amyloid beta-protein precursor (1.0 +/- 0.3 micrograms/ml). These parallel findings suggest a common biochemical marker for these two diseases and further establish the pathogenic relatedness of HCHWA-D and Alzheimer's disease. PMID- 1510362 TI - Juvenile fire setting and the photoparoxysmal response. AB - We report on 3 boys with fire setting, photoparoxysmal responses to intermittent photic stimulation, and temporal lobe electroencephalographic abnormalities. Fire setting resolved and behavior improved with administration of anticonvulsants. PMID- 1510363 TI - Graeme M. Hammond and the ANA. PMID- 1510364 TI - Intracerebral hemorrhage: external validation and extension of a model for prediction of 30-day survival. PMID- 1510365 TI - Oxygen radicals as key mediators in neurological disease: fact or fiction? AB - A free radical is any species capable of independent existence that contains one or more unpaired electrons. Free radicals and other reactive oxygen species are frequently proposed to be involved in the pathology of several neurological disorders. Criteria for establishing such involvement are presented. Development of new methods for measuring oxidative damage should enable elucidation of the precise role of reactive oxygen species in neurological disorders. PMID- 1510366 TI - Distribution of iron in different brain regions and subcellular compartments in Parkinson's disease. PMID- 1510367 TI - Role of iron and iron chelation in dopaminergic-induced neurodegeneration: implication for Parkinson's disease. AB - Recent studies in Parkinson's disease suggest that the degeneration of the nigrostriatal melanin-containing dopaminergic neurons results from toxic effects of free radicals, which are generated during dopamine metabolism in the substantia nigra (SN). This has been linked to the selective accumulation of iron, a known catalyst of radical formation, in the zona compacta of the SN. We have shown that interaction of iron with melanin may result in a high affinity binding of iron to melanin (KD = 13.0 +/- 0.15 nM). Indeed, x-ray analysis of melanized dopamine neurons of parkinsonian SN has shown an interaction of iron with melanin that is absent in control brains. In the presence of excess Fe3+, melanin potentiates iron-induced lipid peroxidation. Since iron chelators prevent lipid peroxidation, we have ascertained the ability of the iron chelator deferoxamine to prevent the lesion of the nigrostriatal dopamine neuron induced by 6-hydroxy dopamine (6-OHDA). Our results demonstrated that intraventricular injection of 130 ng deferoxamine to rats prior to 250 micrograms of 6-OHDA partially prevented the decrease in striatal dopamine content caused by 6-OHDA (56% reduction vs 90%, respectively). This protection was sufficient to produce normal dopamine-related behavioral responses. These results suggest that iron and iron chelators play a crucial role in the process of dopaminergic neurodegeneration and neuroprotection. The latter is further supported by our recent findings that intranigral injection of iron (50 micrograms) resulted in a substantial selective decrease of striatal dopamine (95%) and impaired dopamine related responses. PMID- 1510368 TI - Glutathione in Parkinson's disease: a link between oxidative stress and mitochondrial damage? AB - Several links exist between the two mechanisms of neuronal degeneration (i.e., oxygen radical production and mitochondrial damage) proposed to have a role in Parkinson's disease. Indeed, mitochondria are critical targets for the toxic injury induced by oxygen radicals, and experimental evidence suggests that mitochondrial damage may cause an increased generation of oxygen radicals. A potentially important link between these two mechanisms of neurodegeneration is glutathione. Because of the scavenging activity of glutathione against accumulation of oxygen radicals, its decrease in the brains of parkinsonian patients has been interpreted as a sign of oxidative stress; however, this change may also result from or lead to mitochondrial damage. It is conceivable therefore that regardless of whether oxidative stress or mitochondrial damage represents the initial insult, these toxic mechanisms may both contribute to neuronal degeneration via changes in glutathione levels. PMID- 1510369 TI - Mitochondrial function in Parkinson's disease. The Royal Kings and Queens Parkinson's Disease Research Group. AB - There is increasing evidence for a defect of mitochondrial respiratory chain function in Parkinson's disease. Specific NADH CoQ1 reductase (complex I) deficiency has been identified in the substantia nigra. Available evidence suggests that this defect is confined to the substantia nigra and is not present elsewhere in the parkinsonian brain. The absence of a detectable mitochondrial abnormality in the substantia nigra of patients with multiple system atrophy also suggests that the complex I deficiency in Parkinson's disease is not simply due to an artifact of neuronal degeneration. Evidence for abnormal mitochondrial function in skeletal muscle is conflicting; two studies showed multiple respiratory chain defects and one study was unable to demonstrate any deficiency. A severe deficiency of complex I activity has been found in platelet mitochondria from parkinsonian patients. This finding has not as yet been confirmed. Platelet homogenates do not show the complex I deficiency, however, suggesting that such a preparation may be too insensitive to detect the defect. The role of complex I deficiency in the events that culminate in dopaminergic cell death in Parkinson's disease remains unresolved. It is likely that if this mitochondrial defect is confirmed, it will be related to a number of other factors, including environmental agents, oxidative stress, and genetic predisposition. PMID- 1510370 TI - Criteria for diagnosing Parkinson's disease. AB - Parkinson's disease evolves slowly, and there is current interest in exploring the earliest stages of the disorder, because of new approaches to studying pathogenesis and developing potential neuroprotective treatment. Recognizing early Parkinson's disease is not easy. The certainty of diagnosis increases as the disease advances. To address the problem of identifying Parkinson's disease in its initial phases of clinical expression, we propose the following designated levels of confidence for the diagnosis: (1) clinically possible, (2) clinically probable, and (3) clinically definite. Laboratory support for the diagnosis may be applied to each category. Criteria are provided as a framework underpinning this classification. PMID- 1510371 TI - A pilot trial of high-dose alpha-tocopherol and ascorbate in early Parkinson's disease. AB - High dosages of a combination of alpha-tocopherol and ascorbate were administered to patients with early Parkinson's disease as an open-labeled trial and pilot study to test the endogenous toxic hypothesis of the etiology of Parkinson's disease. Patients receiving concomitant amantadine and anticholinergics were allowed to participate, but those receiving levodopa or dopamine agonists were not. The study was begun prior to the availability of deprenyl. The primary end point of the trial was progression of the disease until patients needed treatment with levodopa or a dopamine agonist. The time when levodopa became necessary in the treated patients was compared to another group of patients followed elsewhere who did not receive antioxidants. The time when levodopa became necessary was extended by 2.5 years in the group receiving alpha-tocopherol and ascorbate. Results of this pilot study suggest that the progression of Parkinson's disease may be slowed by administration of these antioxidants. Controlled clinical trials using double-blind randomization techniques are required to confirm these results. PMID- 1510372 TI - Age-related decline in the dopaminergic nigrostriatal system: the oxidative hypothesis and protective strategies. AB - The anatomical and metabolic deterioration of the dopaminergic (DA) nigrostriatal system with age has been hypothesized to occur due to autodestruction by reactive oxygen intermediates derived from oxidative metabolites of DA. We hypothesized that treatment with a presynaptic agonist to diminish DA turnover should confer a protective effect. Pergolide mesylate, a potent D2 agonist with predominantly presynaptic action, when given in the diet (0.5 mg/kg/day) to male Fischer 344 rats from 3 months of age to 26 months of age, preserved the integrity of both cell bodies and terminals of the nigrostriatal system, partially reversed the age related decline in DA uptake, and had no adverse effects on behavior or postsynaptic DA receptors on striatal neurons compared with age-matched, pair-fed control rats. As a counterpart to this strategy, L-dopa administration (50 mg/kg) to adult male Fischer 344 rats with unilateral nigrostriatal lesions using 6 hydroxy-dopamine, and subsequent fetal mesencephalic grafts resulted in stunted size and neurite outgrowth, diminished tyrosine hydroxylase (TH) expression, diminished behavioral recovery, and diminished ability to reverse lesion-induced D2 receptor changes, compared with saline-treated rats with the same lesion and subsequent graft. This toxic effect, although not seen in intact nigrostriatal systems, may indicate L-dopa toxicity on transplanted DA cells, or on DA cells maximally activated to recover from insult. In 3-month-old male C57BL/6 mice with N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) lesions, spontaneous recovery of the damaged DA nigrostriatal system was seen within 12 weeks.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1510373 TI - Novel inhibitors of iron-dependent lipid peroxidation for neurodegenerative disorders. AB - A considerable body of information supports the occurrence and pathophysiological importance of oxygen radical-mediated lipid peroxidation in acute cerebral damage secondary to traumatic or ischemic injury. Moreover, peroxidative mechanisms have been implicated in chronic neurodegenerative (e.g., Alzheimer's and Parkinson's diseases) and demyelinating (e.g., multiple sclerosis) disorders. Consequently, there has been interest in identification of pharmacological agents with potent ability to interrupt oxygen radical formation or cell membrane lipid peroxidative mechanisms. Our laboratories have developed a novel series of potent lipid peroxidation inhibitors known as the 21-aminosteroids or "lazaroids." One of these compounds, U-74006F or tirilazad mesylate, has shown efficacy in animal models of brain injury and focal cerebral ischemia. In addition, the compound has been found to attenuate the increased lipid peroxidation observed in Alzheimer's brain tissue, to retard anterograde degeneration of motor nerve fibers, and to be effective in decreasing the clinical disease severity and blood-brain barrier disruption observed in the multiple sclerosis model of experimental allergic encephalomyelitis. Another series of antioxidants, the 2-methylaminochromans typified by the compound U-78517F, have been discovered that are even more potent and effective inhibitors of lipid peroxidation than the 21-aminosteroids. PMID- 1510374 TI - Neuroprotective clinical strategies for Parkinson's disease. AB - Increasing knowledge of the role of brain iron in health and disease has prompted consideration of therapeutic strategies aimed at attenuating the effects of iron and its untoward oxidative consequences. The success of this approach is critically dependent on a better understanding of the pathogenesis of Parkinson's disease. The controlled trial "Deprenyl and Tocopherol Antioxidative Therapy of Parkinsonism" (DATATOP) represents a clinical strategy to detect neuroprotective effects of antioxidative interventions. Validation of reliable biological markers of nigral degeneration is central to development of therapies that exert genuine neuroprotective effects in slowing the progression and preventing the onset of Parkinson's disease. PMID- 1510375 TI - Iron and oxygen radicals in brain. AB - The brain has been shown to contain regions with high concentrations of non-heme iron, and some of this iron can be chelated, which suggests that it is in a low molecular mass form. The chelatable iron appears to be responsible for the in vitro peroxidation of homogenized brain tissue lipids. It has been suggested that low molecular mass iron is essential for normal brain functions, and that iron is present in the reduced ferrous state. Recent studies have shown that chelatable iron is often present in micromolar concentrations in apparently normal cerebrospinal fluids (CSF), and that this iron is often increased in certain neurological diseases. Using a molecular recognition assay, based on the in vitro degradation of DNA by bleomycin and chelated ferrous ions, it has been possible to conclude that the low molecular mass iron present in CSF is also in the reduced ferrous state. Ferrous ions are able to transfer electrons to molecular oxygen to form reactive and damaging intermediates of oxygen, some of which are free radicals. Increased levels of iron in brain tissue or CSF, however, are not necessarily synonymous with increased activation of oxygen. Detailed studies of brain iron deposits in neurological diseases are long overdue, and require new and pioneering methodologies to approach the problem. PMID- 1510376 TI - An introduction to the free radical hypothesis in Parkinson's disease. AB - Iron-induced oxidant stress has been implicated in the pathogenesis of Parkinson's disease. An increasing body of evidence now indicates that in Parkinson's disease the environment within the substantia nigra is conducive to the formation of cytotoxic free radicals and cell degeneration. Dopamine neurons may be particularly vulnerable because of the oxidative metabolism of dopamine and the potential of neuromelanin to promote the site-specific accumulation and reduction of iron. This hypothesis has attracted considerable attention because it opens the way for employing antioxidant strategies as possible neuroprotective treatment for Parkinson's disease. Although the concept is appealing, free radicals have not yet been proven to play a role in Parkinson's disease, and many important issues remain to be resolved before the oxidative hypothesis can ultimately be confirmed or refuted. PMID- 1510377 TI - Free radical damage to protein and DNA: mechanisms involved and relevant observations on brain undergoing oxidative stress. AB - Iron mediates damage to proteins and DNA. The mechanisms of damage not only involve iron but also oxygen free radical intermediates. Oxidative damage to DNA causes not only strand breaks, but also formation of specific base adducts, such as 8-hydroxy-2'-deoxyguanosine. Oxidative damage also inactivates certain enzymes such as glutamine synthetase. Novel methods of assessing oxidative damage to tissue, including quantitation of salicylate hydroxylation as an index of hydroxyl free radical flux as well as specific lesions to proteins and DNA, have yielded results that clearly show that ischemia/reperfusion injury to mongolian gerbil brain involves oxidatively damaging events. Aging in gerbil as well as human brain is also associated with increased oxidative damage. Recent novel observations have shown that the spin-trapping agent phenyl alpha-tert butylnitrone (PBN) offers protection in gerbil brain during ischemia/reperfusion injury. We also show that oxidative damage to brain during aging is decreased by chronic administration of PBN. The mechanism of action of PBN may be related to its trapping of specific free radicals, which triggers a cascade of oxidative events that eventually lead to tissue injury. PMID- 1510378 TI - Reactivity of hypervalent iron with biological compounds. AB - Although it is well established that the ferryl (Fe==O2+) and perferryl (Fe==O3+) oxidation states of iron have a beneficial role in enzymatic oxidation and hydroxylation processes, as small complexes that are suspected to be formed in Fenton reactions, they may have deleterious effects on living cells. I discuss the basic chemistry of small hypervalent iron complexes. Their reactivity with biological compounds is illustrated by considering ascorbic acid and essential amino acids. A method is proposed for the determination of the ratio of [.OH]/[ferryl] in Fenton-type reactions. PMID- 1510379 TI - Calcium ions and oxidative cell injury. AB - Exposure of mammalian cells to oxidative stress induced by oxidation-reduction active quinones and other prooxidants results in depletion of intracellular glutathione, followed by modification of protein thiols and loss of cell viability. Protein thiol modification during oxidative stress is normally associated with impairment of various cell functions, including inhibition of agonist-stimulated phosphoinositide metabolism, disruption of intracellular Ca2+ homeostasis, and perturbation of normal cytoskeletal organization. The latter effect appears to be responsible for formation of the numerous plasma membrane blebs typically seen in cells exposed to cytotoxic concentrations of prooxidants. Following disruption of thiol homeostasis in prooxidant-treated cells, there is impairment of Ca2+ transport and subsequent perturbation of intracellular Ca2+ homeostasis, resulting in a sustained increase in cytosolic Ca2+ concentration. This increase in Ca2+ can cause activation of various Ca(2+)-dependent degradative enzymes (e.g., phospholipases, proteases, endonucleases), which may contribute to cell death. In contrast to the cytotoxic effects of excessive oxidative damage, low levels of oxidative stress can lead to activation of enzymes involved in cell signaling. In particular, the activity of protein kinase C is markedly increased by oxidation-reduction-cycling quinones through a thiol/disulfide exchange mechanism, which may represent a mechanism by which prooxidants can modulate cell growth and differentiation. PMID- 1510380 TI - Studies of the mechanism of iron transport across the blood-brain barrier. AB - The mechanism by which iron enters the central nervous system from the blood is not well understood. Iron in blood plasma is totally bound to transferrin (Tf), a major plasma glycoprotein. Tf receptors are present on the blood-brain barrier (BBB) endothelium. It is not known whether iron separates from Tf during its passage across the endothelial cells and then enters the brain by another mechanism, or whether the two proteins enter the brain together. We characterize here the morphological pathway for endocytosis of a monomeric horseradish peroxidase-transferrin conjugate by the rat BBB endothelium. Our results indicate that this conjugate binds to Tf receptors on the luminal BBB, is internalized via clathrin-coated vesicles, enters early or sorting endosomes, and, subsequently, late or recycling endosomes near the Golgi apparatus. No evidence is found for Tf transcytosis. It is likely that iron separates from Tf in early endosomes, which are assumed to be acidic, as they are in other cells, and enters the brain by an as yet undefined pathway. A clonal line of brain capillary endothelial cells that mimics the BBB when grown on permeabilized membranes can transcytose iron provided as Fe55-Tf. This cell line may provide a useful system to determine the pathway that iron uses to enter the brain. We also present evidence that cultured chick embryo forebrain neurons contain a large number of a unique Tf receptor. PMID- 1510381 TI - Iron regulation in the brain: histochemical, biochemical, and molecular considerations. AB - Despite recognition that iron is important for normal neurological function, the proteins involved in maintaining iron homeostasis within the brain have until recently received little attention. In the past few years, studies aimed at determining both general and cellular control of iron in the brain have increased. Histological studies indicate that maintenance of iron homeostasis in the brain is the responsibility of neuroglia and possibly the choroid plexus. Transferrin, the iron transport protein, has been found predominantly in oligodendrocytes in the brain and in myelinating Schwann cells in the peripheral nervous system. The messenger RNA for transferrin is located in the brain in oligodendrocytes and the choroid plexus. Most of the transferrin protein and transcript expression in the brain is dependent on the presence of a mature population of oligodendrocytes. Transferrin is also involved in the transport of iron across the blood-brain barrier via transferrin receptors on brain capillary endothelial cells. The transferrin receptor is also present on cells within the brain. Ferritin, the iron storage protein, and iron are found in the brain in oligodendrocytes and microglia. Additional cells in which iron and ferritin are found are tanycytes, which are associated with the third ventricle. This latter observation raises interesting possibilities regarding the transport of iron from cerebrospinal fluid into the brain. The high iron requirement of the brain coupled with the high susceptibility of the brain to iron-generated peroxidative damage requires stringent regulation of the availability of iron. Consequently, the iron regulatory proteins are central to understanding mechanisms controlling iron-dependent activity at the cellular level, as well as protection of the brain from oxidative damage. The behavior of brain iron regulatory proteins will be a significant factor in future studies of the neurological diseases resulting from brain iron imbalance. We review the contributions of our laboratory to this field over the past 6 years, discuss current projects, and suggest future directions for study. PMID- 1510382 TI - Entry of iron into cells: a new role for the transferrin receptor in modulating iron release from transferrin. AB - The versatile chemistry of iron and the noxious reactions this essential metal may promote have compelled iron-dependent organisms to form specific iron-binding proteins to maintain iron in soluble, nontoxic, and accessible form for cellular needs. A variety of pathways can be traversed by iron to gain access to cells, some available to all cells, others restricted to specialized cells. Of these pathways, the most important and widely functioning is uptake of iron from transferrin in a receptor-mediated process. By regulating expression of the transferrin receptor, iron-dependent cells, including neurons, can be assured an adequate supply of the essential metal while guarding against toxic excess. However, the transferrin receptor functions not only in capturing iron-bearing transferrin, but also in restraining release of iron from transferrin at the cell surface, where iron-catalyzed lipid peroxidation is a threat, while facilitating iron release in acidified endosomes to ensure safe and efficient delivery to the cell. PMID- 1510383 TI - Modulation by neuromelanin of the availability and reactivity of metal ions. AB - Presence of neuromelanin is likely to alter significantly the amount, distribution, reactivity, and consequences of reactivity of metal ions in those parts of the brain that contain neuromelanin. The effects are complex and can be predicted only with detailed knowledge of the system because (1) melanins are strong binders of metal ions and many organic molecules; (2) the effect of binding, depending on the circumstances, can increase or decrease reactivity of metal ions; and (3) melanins can generate and react with oxidation-reduction active species such as hydrogen peroxide, hydroxyl radicals, superoxide anions, and singlet oxygen. Neuromelanin has some significant differences from most other natural melanins because of its mode of formation (by autooxidation rather than enzymatically) and its composition (it probably is a copolymer derived from dopamine and glutathione). It probably is not possible to understand fully the role of metal ions in oxidative damage in the brain without having an adequate understanding of the structure and reactivity of neuromelanin. PMID- 1510384 TI - Comparative techniques for determining cellular iron distribution in brain tissues. AB - Iron is essential for a number of normal brain functions and accumulates in high concentrations in specific regions of the brain. In pathological states, it may further accumulate in these and other areas that are typically low in iron content. The contribution of excess iron to potential central nervous system damage through its ability to donate an electron and to promote oxygen free radical formation has made the nature, location, extent, and process of iron deposition in the brain important areas of investigation. Nevertheless, there is relatively little information currently available on the cellular and subcellular distribution of iron in the central nervous system in either normal or diseased states. We describe and compare a number of the currently available techniques by which iron can be detected within the cellular components of the brain. Histochemical approaches, primarily in the form of the Perls' stain, yields information only on iron in its ferric state and is a relatively insensitive technique. Electron microscopy with x-ray spectrometry can provide positive identification of iron but has limitations regarding morphological verification of the specific cells being probed and also has a relatively high lowest detection limit. Secondary ion mass spectrometry and proton-induced x-ray spectrometry are both expensive, highly complex techniques with greater detection sensitivity, but they have problems identifying the cellular components being analyzed. Finally, laser microprobe mass analysis combines histological localization and identification of probe sites in plastic-embedded histological sections with detection limits in the single part per million range.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1510385 TI - Oxidative stress as a cause of nigral cell death in Parkinson's disease and incidental Lewy body disease. The Royal Kings and Queens Parkinson's Disease Research Group. AB - We examine the evidence for free radical involvement and oxidative stress in the pathological process underlying Parkinson's disease, from postmortem brain tissue. The concept of free radical involvement is supported by enhanced basal lipid peroxidation in substantia nigra in patients with Parkinson's disease, demonstrated by increased levels of malondialdehyde and lipid hydroperoxides. The activity of many of the protective mechanisms against oxidative stress does not seem to be significantly altered in the nigra in Parkinson's disease. Thus, activities of catalase and glutathione peroxidase are more or less unchanged, as are concentrations of vitamin C and vitamin E. The activity of mitochondrial superoxide dismutase and the levels of the antioxidant ion zinc are, however, increased, which may reflect oxidative stress in substantia nigra. Levels of reduced glutathione are decreased in nigra in Parkinson's disease; this decrease does not occur in other brain areas or in other neurodegenerative illnesses affecting this brain region (i.e., multiple system atrophy, progressive supranuclear palsy). Altered glutathione metabolism may prevent inactivation of hydrogen peroxide and enhance formation of toxic hydroxyl radicals. In brain material from patients with incidental Lewy body disease (presymptomatic Parkinson's disease), there is no evidence for alterations in iron metabolism and no significant change in mitochondrial complex I function. The levels of reduced glutathione in substantia nigra, however, are reduced to the same extent as in advanced Parkinson's disease. These data suggest that changes in glutathione function are an early component of the pathological process of Parkinson's disease.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1510386 TI - Why are nigral catecholaminergic neurons more vulnerable than other cells in Parkinson's disease? AB - Although the cause of neuronal death in Parkinson's disease remains unknown, a hyperoxidation phenomenon has been implicated as a potential cytotoxic mechanism. Catecholaminergic neurons containing neuromelanin, an autoxidation byproduct of catecholamines, are more vulnerable in Parkinson's disease than nonmelanized catecholaminergic neurons. High levels of CuZn superoxide dismutase mRNA have been observed in the substantia nigra, suggesting that high levels of oxygen free radicals are indeed produced in the structure. Catecholaminergic neurons surrounded by a low density of glutathione peroxidase cells are more susceptible to degeneration in Parkinson's disease than those well protected against oxidative stress. The nigral content in iron, a compound that exacerbates the production of free radicals in catecholaminergic neurons, is increased in Parkinson's disease. Altogether these data suggest that hyperoxidation may participate in the selective vulnerability of catecholaminergic neurons in Parkinson's disease. PMID- 1510387 TI - Alterations in levels of iron, ferritin, and other trace metals in neurodegenerative diseases affecting the basal ganglia. The Royal Kings and Queens Parkinson's Disease Research Group. AB - Previously we have shown that cell death in the substantia nigra (SN) in Parkinson's disease (PD) is associated with an increase in iron content but a decrease in the level of the iron-binding protein ferritin. Alterations in other metal ion levels were also observed; copper levels were reduced, whereas zinc levels were increased. The importance of these changes in iron, ferritin, and other metal ions in the pathophysiology of PD depends on whether they are specific to the illness. We measured levels of iron, copper, zinc, manganese, and ferritin in postmortem tissue from patients with progressive supranuclear palsy (PSP) and multiple system atrophy (MSA) (which shows pathology in the SN and striatum) and Huntington's disease (HD) (which shows pathological changes in the striatum, compared with control subjects). Total iron levels were elevated in areas of the basal ganglia showing pathological changes in these disorders. In particular, total iron content was increased in SN in PD, PSP, and MSA, but not in HD. Total iron levels in the striatum (caudate nucleus and/or putamen) were increased in PSP, MSA, and HD, but not in PD. There were no consistent alterations in manganese levels in the basal ganglia in any of the diseases studied. Copper levels were decreased in the SN in PD and in the cerebellum in PSP, and were elevated in the putamen and possibly the SN in HD. Zinc levels were only increased in PD in the SN, the caudate nucleus, and the putamen.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1510388 TI - Susceptibility of Pseudomonas species to the novel antibiotics mureidomycins. AB - Strains of Pseudomonas aeruginosa, including imipenem- or ofloxacin-resistant clinical isolates, and some other species in the genus Pseudomonas were inhibited by novel antibiotics of the mureidomycin (MRD) group. On the other hand, almost all other gram-positive and gram-negative bacteria were resistant to MRDs, though the antibiotics potently inhibited the in vitro peptidoglycan synthesis of Escherichia coli and P. aeruginosa. All of the strains in the genus Pseudomonas that were inhibited by less than or equal to 200 micrograms of MRDs per ml were classified into the rRNA groups I and III, and none of the tested strains of rRNA group I were resistant to MRDs, suggesting that these two groups are closely related to each other evolutionary. Among group I strains, P. aeruginosa, P. mendocina, P. stutzeri, and P. alcaligenes were more susceptible than the others, suggesting a closer relationship among these species. PMID- 1510389 TI - Discriminative criteria for Neisseria meningitidis isolates that are moderately susceptible to penicillin and ampicillin. AB - The prevalence of Neisseria meningitidis isolates that are moderately susceptible to penicillin and ampicillin has increased very quickly in Spain; the current prevalences in our hospital are 48.4 and 55.6%, respectively. We studied the reliability of the disk diffusion method for discriminating between fully susceptible (MIC, less than or equal to 0.06 microgram/ml) and moderately susceptible (MICs, 0.12 to 1.0 microgram/ml) isolates. Thirty-eight isolates (12 Pen(s) Amp(s), 18 Penr Ampr, and 8 Pen(s) Ampr) were assayed by the disk diffusion and plate dilution methods by use of disks of 1, 2, 5, and 10 U of penicillin, 2 and 10 micrograms of ampicillin, and 1 microgram of oxacillin on Mueller-Hinton agar with or without 5% sheep blood. Breakpoints were generated, and their discriminative values were determined with a collection of 195 meningococcal strains isolated consecutively from cerebrospinal fluid or blood. None of the strains produced beta-lactamase. Penicillin- and ampicillin susceptible strains (MIC, less than or equal to 0.06 microgram/ml) had oxacillin inhibition zones of greater than or equal to 11 mm on blood agar. Moderate susceptibility to ampicillin and penicillin was suggested by an inhibition zone of less than or equal to 10 mm around the 1-microgram disk and an inhibition zone of less than or equal to 26 mm around the 2-U penicillin disk. We conclude that discrimination between fully susceptible and moderately susceptible populations of N. meningitidis can be accomplished by the disk diffusion method by use of Mueller-Hinton agar plus 5% sheep blood with the 1-microgram oxacillin disk (which is especially suited for screening methods) and the 2-U penicillin disk. The lack of an oxacillin inhibition zone indicates moderate susceptibility to either penicillin or ampicillin or both. PMID- 1510390 TI - Emergence and nosocomial transmission of ampicillin-resistant enterococci. AB - Between 1986 and 1988, the incidence of ampicillin-resistant enterococci increased sevenfold at a university-affiliated hospital. Forty-three patients acquired nosocomial infections with ampicillin-resistant enterococci, most of which were also resistant to mezlocillin, piperacillin, and imipenem. An analysis of plasmid and chromosomal DNAs of isolates revealed that the increase was due to an epidemic of 19 nosocomial infections that yielded closely related strains of Enterococcus faecium and to a significant increase in the incidence of nonepidemic, largely unrelated strains of ampicillin-resistant enterococci. The nonepidemic strains were identified as E. faecium, E. raffinosus, E. durans, and E. gallinarum. A logistic regression analysis revealed that patients with nonepidemic resistant strains were 16 times more likely than controls to have received preceding therapy with imipenem. In our institution, the increase in the incidence of ampicillin-resistant enterococci appears to be due to the selection of various strains of resistant enterococci by the use of imipenem and to the nosocomial transmission of E. faecium and E. raffinosus. PMID- 1510391 TI - Levels of pyrimethamine in sera and cerebrospinal and ventricular fluids from infants treated for congenital toxoplasmosis. Toxoplasmosis Study Group. AB - Pyrimethamine levels in sera, cerebrospinal fluid (CSF), and ventricular fluid were measured by using reversed-phase high-pressure liquid chromatography. The specimens were from 37 infants receiving pyrimethamine for treatment of suspect or proven congenital toxoplasmosis. Pyrimethamine half-life in serum was 64 +/- 12 h when determined by study of terminal-phase kinetics of samples obtained from nine babies. This half-life was significantly different (P = 0.008) from the pyrimethamine half-life (33 +/- 12 h) determined by terminal-phase kinetics for two babies of the same age taking phenobarbital. Serum pyrimethamine levels at various intervals after dosages of pyrimethamine were also lower for infants receiving phenobarbital. Levels measured in sera from babies taking the same dose of pyrimethamine throughout their first year of life did not appear to vary significantly over time or at different ages (P greater than 0.05). Mean +/- standard deviation serum levels 4 h after a pyrimethamine dose were 1.297 +/- 0.54 micrograms/ml for babies taking 1 mg of pyrimethamine per kg of body weight daily and 0.7 +/- 0.26 microgram/ml for babies taking 1 mg/kg each Monday, Wednesday, and Friday. Levels in CSF were approximately 10 to 25% of concomitant levels in serum. Serum folate levels for infants who took 0.64 to 1.7 mg leukovorin per kg ranged from 33 to 663 ng/ml. To determine whether the levels of pyrimethamine in serum and CSF of treated infants were in a range that affected the most virulent, rapidly replicating, and standard laboratory strain of Toxoplasma gondii, effects of various concentrations of pyrimethamine and sulfadiazine on replication of T. gondii in vitro were assessed. The levels of the antimicrobial agents effective in vitro were in the range of levels of pyrimethamine achieved in sera and CSF. Although folinic acid could inhibit the therapeutic effect of pyrimethamine and sulfadiazine in vitro, inhibition was noted only at levels (> or = 4,800 ng/ml) that were considerably higher than the folate levels found in the treated infants' sera. PMID- 1510392 TI - Nucleotide sequence of the ampC-ampR region from the chromosome of Yersinia enterocolitica. AB - The nucleotide sequence of a 3.1-kb region from the chromosome of the Yersinia enterocolitica O:5b strain IP97 containing the gene for an inducible chromosomal cephalosporinase has been determined. The cephalosporinase gene was homologous to other enterobacterial chromosomal cephalosporinase genes, and it was accompanied by a gene homologous to the regulatory ampR gene. The arrangement of genes in the Y. enterocolitica ampCR unit was identical to that in the Enterobacter cloacae and Citrobacter freundii ampCR units. PMID- 1510393 TI - A pleiotropic, posttherapy, enoxacin-resistant mutant of Pseudomonas aeruginosa. AB - An enoxacin-resistant Pseudomonas aeruginosa mutant (G49) isolated during patient therapy was characterized in detail. The G49 mutant was cross resistant to several classes of antibiotics including quinolones, beta-lactams, chloramphenicol, and tetracycline, but not imipenem or aminoglycosides. Compared with its paired pretherapy isolate G48, this mutant had several alterations in outer membrane proteins including a complete loss of the major porin protein OprF and a substantially altered lipopolysaccharide profile. Revertants were selected at a frequency of approximately 1% after enrichment for OprF+ cells on low-salt proteose peptone no. 2 medium. Ninety-seven of these OprF+ revertants were as susceptible to carbenicillin and norfloxacin as the pretherapy isolate. One of these revertants was characterized in more detail and shown to be indistinguishable in all properties from the pretherapy isolate. It is proposed that the multiple-antibiotic-resistance (Mar) phenotype of this mutant resulted from a single pleiotropic mutation. PMID- 1510395 TI - Resistance to beta-lactams in Mycobacterium fortuitum. AB - It is widely assumed that the high level of intrinsic resistance to beta-lactam antibiotics exhibited by mycobacteria results from the combination of factors including permeability to the drugs, beta-lactamase production, and affinity for penicillin-binding proteins (PBPs). We conducted an evaluation of the second and third factors by isolating nitrosoguanidine-induced mutants from the beta lactamase-producing strain Mycobacterium fortuitum ATCC 19542 that displayed either elevated or reduced resistance to various beta-lactam antibiotics. The mutants studied included D1 (a beta-lactamase producer with high penicillin resistance), gamma 27 (a low-level beta-lactamase producer with low penicillin resistance), and D316 (a high-level beta-lactamase producer with high penicillin resistance). In all strains examined, four major PBPs, named 1, 2a, 2b, and 3, with apparent molecular weights of 102,000, 90,000, 87,000, and 50,000, respectively, were found. The MICs of various beta-lactams toward ATCC 19542 and its mutants were considered in the context of beta-lactamase production, the quantity of PBPs synthesized, and their affinities for beta-lactam antibiotics. The data obtained show that beta-lactamase production is likely to be an important factor in the expression of resistance by clinical isolates and that PBP alterations can contribute to resistance at least in laboratory-derived mutants. PMID- 1510394 TI - Vancomycin is not an essential component of the initial empiric treatment regimen for febrile neutropenic patients receiving ceftazidime: a randomized prospective study. AB - The use of vancomycin as part of the initial antibiotic therapy of febrile neutropenic patients has become a controversial issue. Some studies support its incorporation in the initial regimen, and others suggest that vancomycin can be added later. We examined this issue in a prospective, randomized trial. We randomized 127 febrile neutropenic patients to receive either ceftazidime alone or ceftazidime plus vancomycin as the initial empiric antibiotic treatment. We added vancomycin to the ceftazidime arm of the study when fever persisted after 96 h of monotherapy, when new fever occurred after this time, or when a moderately ceftazidime-resistant gram-positive bacterium was isolated. Each of these regimens had similar initial response rates, similar durations of initial fever, similar frequencies of new fever during therapy, similar microbiological cure rates, similar superinfection rates, and similar survival rates. We observed more renal and cutaneous toxicities in patients receiving vancomycin and ceftazidime as initial therapy. We conclude that ceftazidime is appropriate as initial therapy for febrile neutropenic patients and that the addition of vancomycin is appropriate when fever persists after 4 days of monotherapy or when fever recurs following an initial response. PMID- 1510397 TI - Intracellular activity of zidovudine (3'-azido-3'-deoxythymidine, AZT) against Salmonella typhimurium in the macrophage cell line J774-2. AB - The antibacterial effect of zidovudine (AZT) has been demonstrated both in vitro and in vivo with experimental models of gram-negative bacterial infections. It has been associated with the absence or low occurrence of nontyphoid Salmonella infections in AIDS patients treated with AZT. Using the macrophage cell line J774 2, we demonstrate the inhibition of intracellular growth of Salmonella typhimurium by AZT. This effect is obtained with one-half of the MIC (1 microgram/ml) of AZT for S. typhimurium. Inhibition of intracellular growth is observed after 4 h of incubation and persists at 24 h. Maximal inhibition is shown at a concentration of 128 micrograms/ml, and no further effect is observed with higher concentrations. When the inhibitory effect of AZT is compared with that of pefloxacin or that of ceftriaxone at half their MICs (0.2 and 0.02 microgram/ml, respectively), AZT and pefloxacin give better results than ceftriaxone. In this study, using an intracellular model, we show that AZT is able to inhibit the intracellular multiplication of S. typhimurium at a minimal effective concentration lower than the MIC, indicating its potential for antibacterial accumulation in the macrophages. PMID- 1510396 TI - [2',5'-Bis-O-(tert-butyldimethylsilyl)]-3'-spiro-5''-(4''-amino-1'',2''-oxathiole 2'',2''-dioxide) (TSAO) derivatives of purine and pyrimidinenucleosides as potent and selective inhibitors of human immunodeficiency virus type 1. AB - The [2',5'-bis-O-(tert-butyldimethylsilyl)]-3'-spiro-5''-(4''-amino- 1'',2'' oxathiole-2'',2''-dioxide) (TSAO) derivatives of ribofuranosylthymine, uridine, 5 bromouridine, 5-methylcytidine, inosine, and adenosine are potent and selective inhibitors of human immunodeficiency virus type 1 (HIV-1) but not of other retroviruses (HIV-2, simian immunodeficiency virus, or Moloney murine sarcoma virus). The 50% effective concentration (EC50) of the most active TSAO congeners for inhibition of HIV-1 replication ranged from 0.034 to 0.44 microgram/ml. The 50% cytotoxic concentration (CC50) affecting the viability of MT-4 cells ranged from 2.35 to 18 micrograms/ml. The TSAO thymine derivative proved to be a highly selective inhibitor of HIV-1 reverse transcriptase but not of HIV-2 reverse transcriptase and DNA polymerase alpha. Introduction of an alkyl or alkenyl function at N3 of the thymine ring markedly decreased cytotoxicity but did not affect the antiviral activity of the compounds. The most potent (EC50, 0.034 microgram/ml) and most selective (CC50/EC50, 4088) inhibitor of HIV-1 replication proved to be the N3-methyl derivative of (1-[2',5'-bis-O-(tert butyldimethylsilyl)beta-D-ribofuranosyl]thymine)- 3'-spiro-5''-(4''-amino-1'',2'' oxathiole-2'',2''-dioxide). This compound should be considered as a promising drug candidate for the treatment of HIV-1 infections. PMID- 1510398 TI - Pharmacokinetics of single-dose oral ciprofloxacin in infants and small children. AB - The pharmacokinetics of orally administered ciprofloxacin (CIP) was studied in seven infants aged 5 to 14 weeks and nine children aged 1 to 5 years, most of whom were Salmonella carriers. In each case, 15 mg of CIP per kg of body weight was given with water on an empty stomach, and timed serum samples were taken during the following 12 h. The elimination half-life of CIP was significantly (P less than 0.001) longer in the infants (2.73 +/- 0.28 h; mean +/- standard deviation) than it was in the children (1.28 +/- 0.52 h). The area under the serum CIP concentration-time curve (AUC) from time zero to infinity was 16.1 +/- 7.4 mg.h.liter-1 among the infants and 5.3 +/- 3.3 mg.h.liter-1 in the children (P less than 0.01). No significant differences in the maximum concentration in serum, time to maximum concentration in serum, or absorption half-life were observed between the two groups. In contrast, the mean residence time was twofold longer in the infants (4.6 h) than it was in the children (2.4 h; P less than 0.001). The findings suggest that elimination of CIP is particularly rapid in children who just have passed infancy; they may require doses at shorter time intervals than those required by infants or older children or adults. In general, an oral dose of 10 to 15 mg of CIP per kg three times daily seems appropriate for children aged 1 to 5 years. PMID- 1510399 TI - Parasiticidal effect of clindamycin on Toxoplasma gondii grown in cultured cells and selection of a drug-resistant mutant. AB - Clindamycin, which has been reported to have no significant in vitro activity against Toxoplasma gondii, actually markedly inhibits the growth of this parasite in infected human fibroblasts. When measured 3 days after treatment, the concentration required to reduce parasite growth by 50% is about 1 ng/ml. Some observers failed to note this inhibition because of its markedly delayed onset. At 6 ng/ml, clindamycin is parasiticidal, and the rate and extent of parasite killing increase with higher drug concentrations. With the aid of chemical mutagenesis, we isolated a parasite mutant that is approximately 100-fold more resistant to clindamycin than is the wild type. Lincomycin inhibits T. gondii at a higher 50% inhibitory concentration, about 100 ng/ml. The clindamycin-resistant mutant is partially cross-resistant to lincomycin. PMID- 1510400 TI - Susceptibility testing of bacteria recovered from patients with peritonitis complicating continuous ambulatory peritoneal dialysis. AB - Antagonism of antibiotic activity by peritoneal dialysate has been postulated to be a cause of failure of treatment of peritonitis complicating continuous ambulatory peritoneal dialysis. We evaluated by a case-control study whether unexpected treatment failure could be attributed to such antagonism. Bacteria isolated from 34 patient episodes of peritonitis treated with the same regimen of ciprofloxacin monotherapy were studied. Ciprofloxacin was significantly less active in dialysate than in Iso-Sensitest broth (IB). The median MIC in IB was 0.5 microgram/ml, increasing to 2.0 micrograms/ml for both fresh dialysate (FD) (P = 0.003) and pooled dialysis effluent (PDE) (P = 0.03); the median MBC in IB was 8.0 micrograms/ml, increasing to 128.0 micrograms/ml in FD (P = 0.0002) and 64.0 micrograms/ml in PDE (P = 0.02). However, no significant differences were found in the results for patients suffering unexpected treatment failure (relapse of peritonitis) compared with the results for patients whose infection resolved without sequel. In IB the median MICs for relapsers and nonrelapsers were 1.0 and 0.5 microgram/ml, respectively (P = 0.88); median MBCs were 32.0 and 4.0 micrograms/ml (P = 0.19). In FD median MICs for relapsers and nonrelapsers were 2.0 and 1.0 micrograms/ml (P = 0.06); median MBCs were 128.0 micrograms/ml for both groups (P = 0.84). In PDE the median MICs were 2.0 micrograms/ml for both groups (P = 0.78); median MBCs were 256.0 and 64.0 micrograms/ml (P = 0.17). We therefore found no evidence to suggest that antagonism of antibiotic activity by dialysate is a cause of treatment failure or that conventional methods for laboratory susceptibility testing in peritonitis complicating continuous ambulatory peritoneal dialysis should be abandoned in favor of testing in media containing dialysate. PMID- 1510401 TI - Effects of cinnamic acid derivatives on in vitro growth of Plasmodium falciparum and on the permeability of the membrane of malaria-infected erythrocytes. AB - Cinnamic acid derivatives (CADs) are known inhibitors of monocarboxylate transport across plasma and mitochondrial membranes. All derivatives were found to inhibit the growth of intraerythrocytic Plasmodium falciparum in culture, which is in correlation with their hydrophobic character. Parasites at the ring and trophozoite stages were equally susceptible to the different derivatives. This result could be attributed to their inhibition of the transport of lactate, the major product of parasite energy metabolism. However, unexpectedly, it was found that all derivatives also inhibit the translocation of carbohydrates and amino acids across the new permeability pathways induced in the host cell membrane by the parasite. This impediment correlated strictly with CADs' effect on parasite growth. Parasites residing in cells permeabilized by means of Sendai virus were less susceptible to the different drugs, a result which implies that in addition to the direct effect on parasite viability, the drugs may have inhibited some process in the host cell whose function may be vital for parasite growth. The effect of CADs on the ATP levels in infected cells, in virus-treated cells, and in the two cellular compartments of the infected cell revealed that the drugs caused a significant decline in ATP level in the parasite compartment, while they provoked only a small effect on ATP level in the intact cells and the host cell compartment. These observations suggest that CADs inhibit ATP production in the parasite and its utilization by the host cell. PMID- 1510402 TI - Pharmacokinetics and tissue penetration of single-dose cefotetan used for antimicrobial prophylaxis in patients undergoing colorectal surgery. AB - The pharmacokinetics and tissue penetration of cefotetan were studied after a single injection of 2 g given intravenously for antimicrobial prophylaxis to 16 consecutive patients undergoing colorectal surgery. Concentrations in tissue greater than or equal to the MIC for 90% of the main pathogens tested were considered adequate. The elimination half-life at beta phase was 4.6 +/- 1.4 h, the total body clearance was 0.75 +/- 0.19 ml/kg/min, and the volume of distribution was 260 +/- 71 ml/kg. At the time of incision (33 +/- 16 min after the injection), cefotetan concentrations were 14.2 +/- 7 micrograms/g in abdominal-wall fat, 16.4 +/- 1 micrograms/g in epiploic fat, and 163 +/- 62 mg/liter in serum. At the time of surgical anastomosis (151 +/- 54 min), cefotetan concentrations were 33.3 +/- 6 micrograms/g in the colonic wall and 73 +/- 34 mg/liter in serum. Upon closure of the abdomen (216 +/- 76 min), cefotetan concentrations were 6.3 +/- 3 micrograms/g in abdominal-wall fat, 6.1 +/- 4 micrograms/g in epiploic fat, and 64 +/- 38 mg/liter in serum. Cefotetan tissue penetration was 10% into abdominal and epiploic fat and 46% into the colonic wall. Levels in tissue were compared with the MIC for 90% of the most frequently encountered pathogenic germs (Staphylococcus aureus, Bacteroides fragilis, and Escherichia coli). Adequate concentrations in tissue were obtained up to anastomosis but not upon closure. The authors therefore recommend the injection of an additional dose of 1 g before closure in order to ensure optimal efficacy throughout the surgical procedure. PMID- 1510403 TI - The unstable tetracycline resistance gene of Streptomyces lividans 1326 encodes a putative protein with similarities to translational elongation factors and Tet(M) and Tet(O) proteins. AB - Streptomyces lividans contains a genetically unstable tetracycline resistance determinant. Nucleotide sequencing revealed an open reading frame of 1,917 nucleotides. The transcriptional start site was mapped at about 110 bp upstream of the ATG codon. The proposed promoter contains an 8-bp perfect inverted repeat between the -10 and -35 regions. The deduced amino acid sequence showed several motifs which are commonly found in many GTP-binding proteins. On the basis of its amino acid sequence, the presumptive S. lividans 1326 protein belongs to the Tet(M)-Tet(O) group of tetracycline resistance proteins and shows significant similarity to translational elongation factors of prokaryotes and eukaryotes. PMID- 1510404 TI - Isolation of a beta-lactamase-producing, aminoglycoside-resistant strain of Enterococcus faecium. AB - Beta-Lactamase-producing, aminoglycoside-resistant strains of Enterococcus faecalis have been isolated from different geographic areas and are endemic at our institution. We report the isolation of a beta-lactamase-producing, aminoglycoside-resistant strain of E. faecium. The beta-lactamase was plasmid mediated and transferable with high frequency into a plasmid-free E. faecalis recipient strain. MICs suggested that the E. faecium strain also contained intrinsic (chromosomal) resistance to penicillins. PMID- 1510405 TI - Ganciclovir antagonizes the anti-human immunodeficiency virus type 1 activity of zidovudine and didanosine in vitro. AB - In studies examining potential interactions between ganciclovir (GCV) and either zidovudine (AZT) or didanosine (DDI) in H9 cells, GCV was found to consistently reduce the anti-human immunodeficiency virus type 1 potency of both AZT and DDI. In the presence of GCV, the 50% effective doses of AZT and DDI were increased three- to sixfold, depending on the molar ratio of drugs and the measure of human immunodeficiency virus type 1 replication (p24 antigen, reverse transcriptase activity, or infectious virus yield). Multiple dose-effect analysis revealed strong antagonism between GCV and either AZT or DDI (combination indices, 2.2 to 6.7). This antagonistic effect occurred at drug concentrations that were well below the cytotoxic range. At higher drug concentrations, the combination of GCV and AZT was synergistically cytotoxic (combination indices, less than 1.0), whereas GCV and DDI were only additively cytotoxic (combination indices, ca. 1.0). Thus, the combination of GCV with AZT or DDI may result in antiviral antagonism and either synergistic (AZT-GCV) or additive (DDI-GCV) cytotoxicity. PMID- 1510406 TI - Helicobacter pylori infection in a pediatric population: in vitro susceptibilities to omeprazole and eight antimicrobial agents. AB - The in vitro activities of omeprazole and eight antimicrobial agents against 18 clinical strains of Helicobacter pylori isolated from a pediatric population were determined by an agar dilution method. Ampicillin and erythromycin were the most active agents in vitro. All strains were susceptible to azithromycin, ciprofloxacin, doxycycline, metronidazole, and tinidazole. One isolate demonstrated resistance to cefixime (MIC, greater than or equal to 4 micrograms/ml). H. pylori was inhibited by the proton pump inhibitor omeprazole. PMID- 1510407 TI - Effect of pooled human cerebrospinal fluid on the postantibiotic effects of cefotaxime, ciprofloxacin, and gentamicin against Escherichia coli. AB - The killing and postantibiotic effects (PAE) of cefotaxime, ciprofloxacin, and gentamicin against Escherichia coli were determined in Mueller-Hinton broth (MHB) and pooled human cerebrospinal fluid (CSF). MICs performed in MHB and CSF were within one dilution for all antimicrobial agent-organism combinations. At two times the MIC, CSF significantly (P less than 0.05) increased the duration of the PAE compared with MHB when cefotaxime, ciprofloxacin, and gentamicin were used against all strains tested. This effect occurred despite similar reductions in bacterial growth in both fluids after the 2-h antimicrobial agent exposure. We conclude that pooled human CSF markedly increases the PAE of cefotaxime, ciprofloxacin, and gentamicin against E. coli compared with MHB, without affecting bacterial killing. PMID- 1510408 TI - Ofloxacin versus doxycycline for treatment of cervical infection with Chlamydia trachomatis. AB - Women with culture-proven Chlamydia trachomatis cervical infection were randomized to receive either ofloxacin (300 mg) or doxycycline (100 mg), orally twice daily for 7 days. All 56 had negative cultures 5 to 9 days after treatment. Four weeks after treatment, 26 (93%) of 28 ofloxacin-treated patients and all 22 doxycycline-treated patients were cured. We conclude that 300 mg of ofloxacin given twice daily for 7 days provides effective therapy for chlamydial infection of the cervix. PMID- 1510410 TI - Biochemical characterization of the metallo-beta-lactamase CcrA from Bacteroides fragilis TAL3636. AB - The CcrA beta-lactamase from Bacteroides fragilis TAL3636 was cloned into Escherichia coli and purified from inclusion bodies. This group 3 metalloenzyme hydrolyzed most beta-lactam antibiotics, including cephamycins and carbapenems. Following inhibition by chelators, enzyme activity was recovered with the cations Zn2+ and Co2+. Clavulanate and sulbactam were activators; tazobactam at 10 microM inactivated the enzyme. PMID- 1510409 TI - Genetics and regulation of outer membrane protein expression by quinolone resistance loci nfxB, nfxC, and cfxB. AB - Quinolone resistance mutations (cfxB1, marA1, and soxQ1) that reduce porin outer membrane protein OmpF map near 34 min on the Escherichia coli chromosome. Another such mutation, nfxC1, was found in strain KF131 (nfxB, 19 min). nfxC1 and cfxB1 mutants (selected with quinolones) differed slightly but reproducibly from marA1 (selected with tetracycline) and soxQ1 (selected with menadione) mutants in quinolone resistance and linkage to zdd2208::Tn10kan (33.7 min). For nfxB nfxC1 and cfxB1 mutants, as previously shown for marA mutants, resistance and reduced OmpF required the micF locus encoding an antisense RNA complementary to ompF mRNA and were associated with increased micF expression. PMID- 1510411 TI - Detection of gyrA gene mutations associated with ciprofloxacin resistance in methicillin-resistant Staphylococcus aureus: analysis by polymerase chain reaction and automated direct DNA sequencing. AB - A portion of the gyrA gene from amino acid codons 67 to 129 was sequenced in 34 methicillin-resistant Staphylococcus aureus strains (14 isolated in Minnesota, 10 isolated in Indiana, and 10 isolated in Tennessee). Twenty-eight of these strains were ciprofloxacin resistant. Sixteen of the strains contained a Ser----Leu mutation at codon 84; 3 contained strains a Ser----Ala mutation at codon 84; 3 strains contained two mutations, Ser----Leu at codon 84 and Ser----Pro at codon 85; and 6 strains contained a Glu----Lys mutation at codon 88. Six strains were wild type and ciprofloxacin susceptible. Several mutations from amino acid codons 84 through 88 can be associated with high-level quinolone resistance. PMID- 1510412 TI - In vivo antibiotic synergism: contribution of animal models. PMID- 1510413 TI - Evidence that tetracycline analogs whose primary target is not the bacterial ribosome cause lysis of Escherichia coli. AB - The modes of action of atypical tetracyclines that do not directly inhibit bacterial protein synthesis were investigated. The analogs tested, chelocardin, anhydrotetracycline, 6-thiatetracycline, anhydrochlortetracycline, and 4-epi anhydrochlortetracycline, were bactericidal and caused the lysis of Escherichia coli accompanied by the release of the cytoplasmic enzyme beta-galactosidase into the supernatant. Examination by electron microscopy demonstrated that cells exposed to these analogs underwent marked morphological alterations that included the formation of numerous ghosts and the appearance of cellular debris in the culture medium. Although atypical tetracyclines promoted lysis in intact organisms, they did not cause lysis of E. coli spheroplasts, indicating that the analogs do not directly destroy the cytoplasmic membrane. These agents may promote cell lysis and death by interfering with the membrane's electrochemical gradient, which in turn leads to stimulation of autolytic enzyme activity and cellular lysis. The results support recently published data which indicate that tetracyclines are divisible into two classes on the basis of their modes of action. PMID- 1510414 TI - Didanosine and zidovudine resistance patterns in clinical isolates of human immunodeficiency virus type 1 as determined by a replication endpoint concentration assay. AB - Reports of in vitro resistance of human immunodeficiency virus type 1 (HIV-1) to zidovudine (AZT) have raised concerns about the development of resistance to other dideoxynucleosides in clinical use. To address this, we have developed a screening assay which supports the growth of clinical isolates and have applied this to a series of paired isolates from patients entered into a phase I trial of didanosine (DDI). Thirteen patients (10 with AIDS, 3 with AIDS-related complex) who had been exposed to AZT for a mean of 6.5 months (range, 1 to 13 months) were treated with DDI at 750 mg/day. Paired isolates were obtained pretherapy and after a mean of 58 weeks (range, 21 to 90) of DDI therapy by coculture of peripheral blood mononuclear leukocytes (PBLs) with phytohemagglutinin-stimulated donor PBLs. Isolates were passaged only one additional time in PBLs and then tested in parallel in a microtiter assay with phytohemagglutinin-stimulated donor PBLs as targets. PBLs were infected with 10(5) 50% tissue culture infectious doses per 10(7) cells and exposed to DDI (1 to 50 microM) or AZT (0.01 to 100 microM), and supernatants were assayed for the HIV p24 antigen at 7 days postinfection. Control AZT-susceptible and resistant isolates were included. The median pre- and posttherapy DDI susceptibilities of the 13 pairs of isolates were 10.0 microM (range, 1 to 25 microM) and 17.5 microM (range, 2.5 to 50 microM), respectively (P = 0.036; Wilcoxon signed-rank test). These studies thus indicated that (i) the susceptibility to DDI tends to mildly decrease with drug exposure; (ii) the susceptibility to AZT improves with time off AZT; (iii) baseline susceptibilities to DDI have a wide range, and the CD4 response may correlate with the initial susceptibility; and (iv) a PBL-based microtiter assay is useful for screening clinical isolated for dideoxynucleoside susceptibility profiles. PMID- 1510415 TI - In vitro inhibition of human immunodeficiency virus (HIV) type 1 replication by C2 symmetry-based HIV protease inhibitors as single agents or in combinations. AB - C2 symmetry-based human immunodeficiency virus (HIV) protease inhibitors were examined in vitro as single agents or in combination with 3'-azido-2',3' dideoxythymidine (AZT) or 2',3'-dideoxyinosine for activity against HIV type 1 (HIV-1). Ten C2 symmetry-based or pseudo-C2 symmetry-based HIV protease inhibitors were active against a laboratory strain (HIV-1IIIB) in the HIV-1 cytopathic effect inhibition assay. Three inhibitors, A75925, A76928, and A77003, selected to represent a range of aqueous solubility and antiviral activity, were active against four different HIV-1 strains tested. These three inhibitors exhibited a significant inhibition of the cytopathic effect of HIV-1 against the CD4+ ATH8 cell line, with 90% inhibitory concentrations ranging from 0.1 to 4 microM. Cellular toxicity was negligible at up to 20 microM. Furthermore, they completely inhibited the replication of monocytotropic strain HIV-1Ba-L in purified monocytes and macrophages at 0.75 to 2 microM. Potent inhibitory activity against a primary HIV-1 isolate and an AZT-resistant HIV-1 variant was also observed for all three inhibitors in phytohemagglutinin-activated peripheral blood mononuclear cells. When these three HIV protease inhibitors and AZT or 2',3'-dideoxyinosine were used in combinations against a primary HIV isolate in phytohemagglutinin-activated peripheral blood mononuclear cells and the results were analyzed with the COMBO program package, their antiviral activities were identified to be synergistic in some cases and additive in others. The present data warrant further investigations of these compounds as potential antiviral agents for the therapy of HIV infections. PMID- 1510416 TI - Excretion of cefprozil into human breast milk. AB - The excretion of cefprozil into breast milk in nine healthy, lactating female subjects was investigated. Each subject received a single 1,000-mg oral dose of cefprozil consisting of cis and trans isomers in an approximately 90:10 ratio. Serial blood, urine, and breast milk samples were collected and analyzed for the concentrations of the cis and trans isomers by a specific high-pressure liquid chromatography-UV assay. The mean pharmacokinetic parameters for both isomers were essentially the same. The mean peak concentrations in plasma for the cis isomer were 14.8 micrograms/ml, and the area under the concentration curve was 54.8 micrograms.h/ml. The mean values of elimination half-life, renal clearance, and urinary excretion for the cis isomer were 1.69 h, 164 ml/min, and 60%, respectively. The mean concentrations in milk of the cis isomer over a 24-h period ranged from 0.25 to 3.36 micrograms/ml, with the maximum concentration appearing at 6 h after dosing. The average maximum concentration in milk of the trans isomer was less than 0.26 micrograms/ml. The concentrations of the trans isomer in plasma and in breast milk were about 1/10 of those for the cis isomer. Less than 0.3% of the dose was excreted in breast milk for both isomers of cefprozil. Even if one assumes that the concentration of cefprozil in milk remains constant at 3.36 micrograms/ml (the highest concentration of cefprozil observed in breast milk), an infant ingesting an average of 800 ml of milk per day will be exposed to a maximum amount of about 3 mg of cefprozil per day. This value represents about 0.3% of the maternal dose. Low excretion of cefprozil in breast milk and the excellent safety profile of cefprozil suggest that this cephalosporin may be administered to nursing mothers when indicated. PMID- 1510417 TI - Inhibitory potency of quinolone antibacterial agents against cytochrome P450IA2 activity in vivo and in vitro. AB - Inhibition of cytochrome P450IA2 activity is an important adverse effect of quinolone antibacterial agents. It results in a prolonged half-life for some drugs that are coadministered with quinolones, such as theophylline. The objective of the study described here was to define the parameters for quantifying the inhibitory potencies of quinolones against cytochrome P450IA2 in vivo and in vitro and to investigate the relationship between the results of both approaches. Cytochrome P450IA2 activity in vitro was measured by using the 3 demethylation rate of caffeine (500 microM) in human liver microsomes. The inhibitory potency of a quinolone in vitro was determined by calculating the decrease in the activity of cytochrome P450IA2 caused by addition of the quinolone (500 microM) into the incubation medium. The mean values (percent reduction of activity without quinolone) were as follows: enoxacin, 74.9%; ciprofloxacin, 70.4%; nalidixic acid, 66.6%; pipemidic acid, 59.3%; norfloxacin, 55.7%; lomefloxacin, 23.4%; pefloxacin, 22.0%; amifloxacin, 21.4%; difloxacin, 21.3%; ofloxacin, 11.8%; temafloxacin, 10.0%; fleroxacin, no effect. The inhibitory potency of a quinolone in vivo was defined by a dose- and bioavailability-normalized parameter calculated from changes of the elimination half-life of theophylline and/or caffeine reported in previously published studies. Taking the pharmacokinetics of the quinolones into account, it was possible to differentiate between substances with and without clinically relevant inhibitory effects by using results of in vitro investigations. The in vitro test described here may help to qualitatively predict the relevant drug interactions between quinolones and methylxanthines that occur during therapy. PMID- 1510418 TI - Therapy of experimental meningitis due to Salmonella enteritidis. AB - In many areas of the developing world, Salmonella spp. account for greater than 50% of the gram-negative enteric organisms isolated from cerebrospinal fluid (CSF). The response of Salmonella meningitis to conventional therapy (chloramphenicol and/or ampicillin) is slow, complications arise frequently, and mortality rates of 60 to 80% are common. Two newer agents, ceftriaxone and imipenem, were compared with ampicillin, chloramphenicol, and trimethoprim sulfamethoxazole (TMP-SMX) in the therapy of experimental Salmonella meningitis beginning 14 h after intracisternal inoculation and continued by constant intravenous infusion for 8 h. Drug concentrations in serum and CSF closely approximated those achieved in the sera and CSF of humans receiving standard parenteral regimens. Penetration into purulent CSF [(concentration of drug in CSF/concentration of drug in serum) x 100] ranged from 18 to 41%. The rate of bacterial killing in CSF was significantly (P less than 0.001) more rapid during therapy with ceftriaxone and imipenem than it was during therapy with chloramphenicol or TMP-SMX. Ceftriaxone and imipenem sterilized the CSF of six of seven animals at 8 h, whereas it sterilized the CSF of three of eight animals treated with ampicillin (P = 0.18), one of eight animals treated with chloramphenicol, and none of seven animals treated with TMP-SMX (P less than or equal to 0.01; ceftriaxone or imipenem versus chloramphenicol or TMP-SMX). New beta-lactams, including ceftriaxone and imipenem, appear to be effective therapy against Salmonella spp. in this animal model and deserve further evaluation in humans. PMID- 1510419 TI - Dissociation of the antimicrobial activity of bacitracin USP from its renovascular effects. AB - Bacitracin is a nephrotoxic antibiotic that has recently been shown to induce contractile effects in aortas isolated from rabbits by stimulating receptors for 5-hydroxytryptamine (5-HT). The possible renovascular actions of this antibiotic were investigated. Bacitracin USP increased the vascular resistance in a concentration-dependent manner (9 to 175 micrograms/ml) in rat kidneys perfused with a constant flow of Krebs solution. This was significantly inhibited by 5-HT antagonists, but only partially at the higher bacitracin concentration. An antagonist of the chemotactic peptide fMet-Leu-Phe failed to influence the pressor effect of bacitracin in rat kidneys. Indomethacin modestly reduced the effect of all potent pressor agents in the rat organ. Bacitracin USP was separated in several fractions by using C18 reverse-phase chromatography. Two distinct fractions were vasoconstrictive when infused in rat kidneys; both fractions were 5-HT mimetics. These peaks were different from the major antibiotic peak, bacitracin A, which was identified by using analytical high pressure liquid chromatography, mass spectrometry, and inhibition of Micrococcus luteus growth. The less polar vasoactive peak corresponded to at least two minor peptides of the bacitracin family. The most abundant of these vasoactive peptides had no direct contractile effect on an aorta isolated from a rabbit, but a preliminary metabolic study in rat kidneys suggests that it is apparently transformed into a potent 5-HT agonist that is active on the aorta preparation. Bacitracin A, the major constituent of bacitracin with antimicrobial activity, had no vasoconstrictor effect in the test systems that we used; however, we did rule out the possibility that the renovascular stimulants found in the bacitracin mixture do not derive spontaneously or by biotransformation from the antibacterial forms of bacitracin. PMID- 1510420 TI - Effect of antacid on the bioavailability of cefprozil. AB - The effect of antacid on the bioavailability of cefprozil was investigated in a two-way crossover study. Eight healthy male subjects received a single 500-mg oral dose of cefprozil with and without coadministration of 30 ml of an antacid suspension containing magnesium hydroxide and aluminum hydroxide (Maalox). Cefprozil consists of cis and trans isomers in an approximate 90:10 ratio. When cefprozil was administered alone (treatment A), the mean maximum concentrations (Cmax) of the cis and trans isomers were 9.2 and 1.2 micrograms/ml, respectively. When cefprozil was coadministered with Maalox (treatment B), the Cmax values of the cis and trans isomers were 8.7 and 1.3 micrograms/ml, respectively. The mean values of the area under the curve from time zero to infinity (AUC0-infinity) were 27.7 and 3.5 micrograms.h/ml for treatment A and 27.5 and 3.5 micrograms.h/ml for treatment B for the cis and trans isomers, respectively. The other pharmacokinetic parameters, time to Cmax, elimination half-life, mean residence time, renal clearance, and percent urinary excretion, were essentially the same for the two isomers. The respective values of the elimination half-life for the cis and trans isomers were 1.36 and 1.32 h for treatment A and 1.36 and 1.42 h for treatment B. Mean urinary excretion was 63 and 60% for treatment A and 58 and 56% for treatment B for the cis and trans isomers, respectively. No significant differences between the two treatments were found for any of the pharmacokinetic parameters for either isomer. For the cis isomer, bioavailability point estimates (90% confidence intervals) of the mean Cmax and AUG0-infinity values for the Maalox treatment relative to those for the reference treatment were 95% (87%, 103%) and 99% (95%, 104%), respectively. For the trans isomer, the value were 109% (92%, 126%) for Cmax and 97% (88%, 106%) for AUC0-infinity. On the basis of the results of this study, it is concluded that the bioavailability of cefprozil is not affected by the coadministration of Maalox. PMID- 1510421 TI - Metabolic disposition of DQ-2556, a new cephalosporin, in rats, rabbits, dogs, and monkeys. AB - The metabolic disposition of DQ-2556 was studied in rats, rabbits, dogs, and monkeys after an intravenous administration of 20 mg of 14C-labeled drug per kg of body weight. The serum data were analyzed by the two-compartment open model. The mean half-lives for the drug in serum at excretion phase were 18.1, 54.4, 21.8, and 63.6 min in rats, rabbits, dogs, and monkeys, respectively. The volume of distribution and total body clearance ranged from 0.18 to 0.30 liter/kg and 0.065 to 0.45 liter/h/kg, respectively. This compound was distributed to the tissues rapidly and well, especially to the kidney, trachea, liver, thyroid, skin, and lung. Tissue concentrations declined rapidly in a few hours and then very slowly. However, no accumulation was observed in any tissues. The results of a protein-binding study by ultracentrifugation indicated that DQ-2556 was 20 to 30% bound to serum proteins in animals and its affinity was low. Almost 90% of the administered radioactivity was excreted into urine in all species. Biliary excretion in rats was 3.1% of the dose. Nearly 70% of the dose or more was excreted into urine as unchanged drug, and the amounts of urinary metabolites were small except in rabbits, in which substantial amounts of polar metabolites were detected. PMID- 1510422 TI - Therapy of experimental murine brucellosis with streptomycin, co-trimoxazole, ciprofloxacin, ofloxacin, pefloxacin, doxycycline, and rifampin. AB - Mice infected with Brucella melitensis were treated with streptomycin, co trimoxazole, ciprofloxacin, doxycycline, and rifampin intraperitoneally and with ciprofloxacin, ofloxacin, pefloxacin, doxycycline, and rifampin orally for 14 to 21 days. Doxycycline- and rifampin-treated animals (either route) demonstrated a cure rate significantly better than that of controls. Longer therapy periods were associated with a significantly better outcome. Therapy failure was observed in all mice treated with ciprofloxacin, ofloxacin, and pefloxacin administered orally as well as in mice treated intraperitoneally with ciprofloxacin. Our findings demonstrate that treatment of experimental brucellosis in mice with doxycycline and rifampin yields therapeutic results that are superior to those yielded by treatment with quinolones. PMID- 1510423 TI - Pharmacologic modulation of interleukin-1 expression by amphotericin B-stimulated human mononuclear cells. AB - Fever and chills occur frequently with amphotericin B (AB) administration, but the mechanism that causes these reactions has not been definitively established. A variety of proinflammatory cytokines, including interleukin-1 (IL-1) and tumor necrosis factor, have been shown to be important mediators of fever. In order to clarify the cellular and biochemical responses associated with AB-induced fever, the experiments described sought to (i) establish whether human mononuclear cells exposed to AB in vitro expressed IL-1 beta, (ii) evaluate whether clinically used premedications for fever prophylaxis in AB-treated patients were effective in down-regulating IL-1 beta expression in vitro, (iii) evaluate whether methylxanthine agents with immunomodulatory actions effected in vitro IL-1 beta expression, and (iv) define the dose and time dependency of the modulating effects. Peripheral blood mononuclear cells were isolated by density centrifugation and resuspended to 10(6) cells per ml in culture wells of Linbro plates. When cocultured for 2 h with human mononuclear cells, both Escherichia coli lipopolysaccharide and AB stimulated IL-1 beta expression in a dose-related fashion. AB-induced IL-1 beta expression was suppressed by hydrocortisone (HC), pentoxifylline, and an investigational theobromine, A81-3138, in a linear, dose related manner. In contrast, indomethacin, meperidine, and diphenhydramine had no effect on IL-1 beta expression. Our in vitro data indicate that serum HC concentrations of greater than 1 to 2 micrograms/ml may be sufficient to modulate IL-1 beta expression. Pentoxifylline and A81-3138 may also be effective in modulating IL-1 beta expression by mononuclear cells at concentrations achievable in serum. These new agents may prove to be effective alternatives to HC or may be added with HC to suppress febrile reactions secondary to AB administration. Clinical studies with pentoxifylline as a premedication for AB seem warranted. PMID- 1510425 TI - Epidemiology of plasmid-mediated beta-lactamases in enterobacteria Swedish neonatal wards and relation to antimicrobial therapy. AB - TEM-1, OXA-1, SHV-1, and related beta-lactamases in fecal isolates from 953 infants in 22 Swedish neonatal intensive care units were studied by DNA hybridization. TEM-1- and OXA-1-positive isolates were always Escherichia coli and represented 86 and 8%, respectively, of the ampicillin-resistant isolates of this species. SHV-1 was found in 16% of the Klebsiella sp. (mainly Klebsiella pneumoniae) isolates. TEM-1 and SHV-1 occurred in 14 and 16 units and in up to 64 and 26% of the neonates, respectively. On average, two to four different biochemical phenotypes per species per ward were positive for each beta lactamase. All but 1 of the 33 E. coli phenotypes found to be TEM-1 positive were uniformly positive for the beta-lactamase gene, whereas some of the phenotypes found to be positive for OXA-1 (2 of 3) and SHV-1 (6 of 70) were occasionally negative for the respective genes. The occurrence of the three beta-lactamases studied tended to be associated with local ampicillin usage (correlation coefficient, 0.31 to 0.39; P greater than 0.05). Of the neonates receiving ampicillin, 30% carried TEM-1-positive E. coli, compared with 13% for cephalosporin-treated neonates and 15% for untreated neonates (P less than or equal to 0.001). The corresponding rates for SHV-1 in Klebsiella spp. were 18, 13, and 9% (P less than or equal to 0.01). Ampicillin is thus a significant risk factor for the maintenance of the most prevalent gram-negative plasmid-mediated beta-lactamases in hospitalized neonates. PMID- 1510424 TI - Human immunodeficiency virus type 1 protease inhibitors irreversibly block infectivity of purified virions from chronically infected cells. AB - Synthetic peptide analog inhibitors of human immunodeficiency virus type 1 (HIV 1) protease were used to study the effects of inhibition of polyprotein processing on the assembly, structure, and infectivity of virions released from a T-cell line chronically infected with HIV-1. Inhibition of proteolytic processing of both Pr55gag and Pr160gag-pol was observed in purified virions from infected T cells after treatment. Protease inhibition was evident by the accumulation of precursors and processing intermediates of Pr55gag and by corresponding decreases in mature protein products. Electron microscopy revealed that the majority of the virion particles released from inhibitor-treated cells after a 24-h treatment had an immature or aberrant capsid morphology. This morphological change correlated with the inhibition of polyprotein processing and a loss of infectivity. The infectivity of virion particles purified from these chronically infected cell cultures was assessed following treatment with the inhibitor for 1 to 3 days. Virions purified from cultures treated with inhibitor for 1 or 2 days demonstrated a 95- to 100-fold reduction in virus titers, and treatment for 3 days resulted in complete loss of detectable infectivity. The fact that virions from treated cultures were unable to establish infection over the 7- to 10-day incubation period in the titration experiments strongly suggests that particles produced by inhibitor-treated cells were unable to reactivate to an infectious form when they were purified away from exogenous protease inhibitor. Thus, a block of HIV-1 protease processing of viral polyproteins by specific inhibitors results in a potent antiviral effect characterized by the production of noninfectious virions with altered protein structures and immature morphologies. PMID- 1510426 TI - Pharmacokinetic profiles of ciprofloxacin after single intravenous and oral doses. AB - Ciprofloxacin was administered to 12 healthy male volunteers at doses of 300 and 400 mg intravenously (i.v.) and 500 and 750 mg orally in a randomized, double blind, single-dose, four-period crossover study. On each treatment day, each subject received both oral and i.v. formulations, one of which was a placebo. Blood and urine samples were obtained through 24 h postdose. By each dosing route, the pharmacokinetic profiles were dose proportional. The 400-mg i.v. dose was equivalent to the 500-mg oral dose with respect to the area under the concentration-time curve and was equivalent to the 750-mg oral dose with respect to the maximum concentration of ciprofloxacin in serum. The oral bioavailability was 78.0%. The steady-state volume of distribution averaged 178 liters, and the terminal half-life in serum after i.v. dosing was approximately 4.3 h. Renal clearance accounted for approximately 60% of total body clearance. No significant adverse events were associated with either route of administration. PMID- 1510427 TI - Establishment of aging biofilms: possible mechanism of bacterial resistance to antimicrobial therapy. PMID- 1510428 TI - In vitro and in vivo activities of SCE-2787, a new parenteral cephalosporin with a broad antibacterial spectrum. AB - SCE-2787, a new cephalosporin having a condensed azolium moiety in the 3 position and an aminothiadiazolyl group in the 7 beta side chain, was evaluated for its in vitro and in vivo activities in comparison with those of ceftazidime, flomoxef, cefpirome, and E1040. Against methicillin-susceptible strains of Staphylococcus aureus and Staphylococcus epidermidis, SCE-2787 was more active than ceftazidime and E1040 and was as active as flomoxef and cefpirome, with MICs for 90% of strains tested (MIC90s) being 1.56 micrograms/ml or less. SCE-2787 was also active against Pseudomonas aeruginosa, for which the MIC90 was 6.25 micrograms/ml, which was lower than that of cefpirome and comparable to that of ceftazidime. SCE-2787 was marginally active against methicillin-resistant strains of staphylococci and Enterococcus faecalis, although its MIC90s were the lowest among those of the antibiotics tested. The activities of SCE-2787 against Streptococcus species, most members of the family Enterobacteriaceae, and Haemophilus influenzae exceeded those of ceftazidime and flomoxef and were comparable to those of cefpirome. Furthermore, MIC90s of SCE-2787 were significantly lower than those of ceftazidime for ceftazidime-resistant isolates of Citrobacter freundii and Enterobacter cloacae. SCE-2787 was resistant to hydrolysis by various types of beta-lactamases, including the Bush group 1 beta lactamases, and had low affinities for these enzymes, with Km or Ki values of greater than 100 microM. The in vitro activity of SCE-2787 was reflected in its efficacy in mouse protection tests. Thus, SCE-2787 appears to be a promising cephalosporin that should be further evaluated in clinical trials. PMID- 1510429 TI - Mapping and characterization of multiple chromosomal factors involved in methicillin resistance in Staphylococcus aureus. AB - Chromosomal factors, termed fem or aux factors, are needed for the expression of methicillin resistance in methicillin-resistant (Mcr) Staphylococcus aureus; also needed is the mec-encoded low-affinity penicillin-binding protein PBP 2'. These factors make up part of the normal set of genes present in susceptible and resistant strains of S. aureus and can be identified by Tn551-mediated insertional inactivation of the methicillin resistance. In this study, we characterized different Tn551 inserts and mapped them into four distinct loci on the SmaI chromosomal map of S. aureus NCTC 8325, thereby identifying two new loci which code for fem factors. The largest fragment, SmaI-A, carries three loci, two coding for both closely linked factors femA and femB and a novel third locus (femC) that is not linked to the other two. An additional, fourth, locus, femD, was identified in fragment SmaI-I. femA and femB inactivation reduced overall methicillin resistance, whereby femB had less of an influence on the resistance level. femC and femD inactivation reduced mainly the basal resistance level in heterogeneously Mcr strains and had less of an impact on the subpopulation with high-level resistance. Inactivation of either of these factors was shown to have no influence on the production of PBP 2', the main factor mediating methicillin resistance. In addition, no changes were observed in the banding patterns of the major autolysins in whole-cell extracts of the fem mutants, suggesting that the reduced cell wall turnover and autolysis observed in some of the insertionally inactivated strains were due to changes either of the substrate or in the autolysin control. PMID- 1510430 TI - Epithelial cells in culture as a model for the intestinal transport of antimicrobial agents. AB - The bioavailabilities of orally administered drugs depend to a great extent on their capability of being transported across the intestinal mucosa. In an attempt to develop an in vitro model for studying the intestinal transport of drugs, we used an intestinal epithelial cell line (Caco 2) derived from a human colon adenocarcinoma. A renal epithelial cell line (MDCK) was also used to determine the tissue specificity of drug transport. These cell lines, which were grown on filters, form a monolayer of well-polarized cells coupled by tight junctions and can be used for transcellular transport experiments. We studied the transport of nine antimicrobial agents with different physicochemical and pharmacokinetic characteristics using these epithelial cell monolayers to determine whether this model could be predictive of oral bioavailability. The transepithelial passage was assayed from the apical (AP) to the basolateral (BL) side and in the opposite direction (BL to AP) in both cell lines. Radioactively labeled mannitol was used to monitor the intactness of the cell monolayer during drug passage. The results indicated that all antimicrobial agents tested tended to behave in vitro generally according to their known in vivo absorptive characteristics. In addition, the use of epithelia from different tissues enabled us to divide the drugs into four groups according to their behaviors and suggested the existence of different transport mechanisms. In particular, two antibiotics, gentamicin and teicoplanin, showed no passage in either direction or cell line, in accordance with their very poor in vivo absorbances after oral administration. In contrast, rifapentine, rifampin, and nalidixic acid passed very efficiently at similar rates in both directions and cell lines in a concentration-dependent, nonsaturable manner, which is suggestive of passive diffusion down a concentration gradient. Of the remaining drugs, isoniazid and novobiocin sodium showed some differences in passage between the two cell lines and, given their ionized state at the pH that was used, may use the paracellular route. Finally, trimethoprim and D-cycloserine exhibited differences in passage both with respect to polarity and cell line; in particular, trimethoprim had a faster rate of passage only in Caco 2 cells and in the BL to AP direction, while D-cycloserine was exclusively transported by Caco 2 cells in the AP to BL direction. In both cases it is possible that active transport mechanisms are involved. PMID- 1510431 TI - Lack of pharmacokinetic interaction between cefepime and amikacin in humans. AB - The interaction potential between cefepime and amikacin was investigated in a steady-state pharmacokinetic study in 16 healthy male subjects. Eight subjects (group A) received a first course of 2,000 mg of cefepime; this was followed by a second course of 2,000 mg of cefepime with 300 mg of amikacin and a third course of 2,000 mg of cefepime. Eight other subjects (group B) received a first course of 300 mg of amikacin, a second course of 300 mg of amikacin with 2,000 mg of cefepime, and a third course of 300 mg of amikacin. Each course consisted of four consecutive doses administered every 8 h as 30-min intravenous infusions. Serial plasma and urine samples, which were collected after administration of the fourth dose of each course, were assayed for cefepime and/or amikacin by validated high performance liquid chromatographic assays. Trough levels of cefepime and amikacin indicated that these antibiotics attained a steady state prior to administration of the fourth dose of each course. Key pharmacokinetic parameters for each antibiotic were determined by noncompartmental methods. The peak concentrations of cefepime and amikacin in plasma when the drugs were given alone were about 160 and 27 micrograms/ml, respectively. Levels of each antibiotic in plasma declined, with an apparent half-life of approximately 2.2 h. Urinary recovery of cefepime and amikacin accounted for more than 85% of the administered dose of each antibiotic. Mean renal clearances for cefepime and amikacin ranged from 79 to 95 ml/min and suggested that glomerular filtration is the primary excretion mechanism. The results of the statistical analyses indicated that the pharmacokinetic parameters of cefepime following the concurrent administration of amikacin and following the discontinuation of the amikacin following the concurrent administration of cefepime and following the discontinuation of the cefepime therapy were not significantly altered. Cefepime and amikacin can be coadministered to patients with normal renal function by using the standard recommended dosing regimens. PMID- 1510432 TI - Pharmacokinetics of cefepime in patients undergoing continuous ambulatory peritoneal dialysis. AB - The pharmacokinetics of cefepime were studied in 10 male patients receiving continuous ambulatory peritoneal dialysis therapy. Five patients received a single 1,000-mg dose and the other five received a single 2,000-mg dose; all doses were given as 30-min intravenous infusions. Serial plasma, urine, and peritoneal dialysate samples were collected; and the concentrations of cefepime in these fluids were measured over 72 h by using a high-performance liquid chromatographic assay with UV detection. Pharmacokinetic parameters were calculated by noncompartmental methods. The peak concentrations in plasma and the areas under the plasma concentration-versus-time curve for the 2,000-mg dose group were twice as high as those observed for the 1,000-mg dose group. The elimination half-life of cefepime was about 18 h and was independent of the dose. The steady-state volume of distribution was about 22 liters, and values for the 1,000- and 2,000-mg doses were not significantly different. The values for total body clearance and peritoneal dialysis clearance were about 15 and 4 ml/min, respectively. No dose dependency was observed for the clearance estimates. Over the 72-h sampling period, about 26% of the dose was excreted intact into the peritoneal dialysis fluid. For 48 h postdose, mean concentrations of cefepime in dialysate at the end of each dialysis interval exceeded the reported MICs for 90% of the isolates (MIC90s) for bacteria which commonly cause peritonitis resulting from continuous peritoneal dialysis. A parenteral dose of 1,000 or 2,000 mg of cefepime every 48 h would maintain the antibiotic levels in plasma and peritoneal fluid above the MIC90s for the most susceptible bacteria for the treatment of systemic and intraperitoneal infections [corrected]. PMID- 1510433 TI - Vancomycin resistance in Enterococcus gallinarum. AB - The vancomycin resistance expressed by several strains of Enterococcus gallinarum was studied. Resistance was expressed constitutively, as demonstrated by analysis of growth and inhibition of peptidoglycan synthesis. E. gallinarum strains were moderately resistant to vancomycin (MIC, 16 micrograms/ml) but were as susceptible as vancomycin-susceptible enterococci to the glycopeptides, teicoplanin, A35512B, A47934, A4103A, and A41030E and the glycopeptide actaplanins A1, B2, and C1. Vancomycin resistance in E. gallinarum was inhibited by beta-lactam antibiotics at concentrations that saturated penicillin-binding protein 6 (PBP 6), as demonstrated by binding competition experiments. Spontaneous mutants (frequency, 10(-8)) were two- to fourfold more resistant to beta-lactam inhibition of vancomycin resistance than the parent strain. PBP binding competition experiments suggested that PBP 6 in the mutants bound less cefotaxime, while binding of penicillin and cefoxitin was unaffected. Both a bioassay method and high-performance liquid chromatography showed that E. gallinarum membranes have enzymatic activity which modifies a model pentapeptide yielding a product that is thought to be a tetrapeptide. This activity could be a D,D-carboxypeptidase. In both the parent E. gallinarum strain and its derivatives that were resistant to the synergistic drug combination, the activity was inhibited by beta-lactams at concentrations which correlated with those that inhibit vancomycin resistance and those that saturate PBP 6. These results suggest the possibility that PBP 6 may be involved in the vancomycin resistance of E. gallinarum and that the putative D,D-carboxypeptidase activity seen in E. gallinarum membranes may be attributable to PBP 6. PMID- 1510434 TI - Pharmacokinetics of imipenem in serum and skin window fluid in healthy adults after intramuscular or intravenous administration. AB - The pharmacokinetic profiles of imipenem after intramuscular (i.m.) and intravenous injections were examined in adult volunteers. Levels of imipenem in serum after i.m. injection of a microcrystalline suspension of imipenem cilastatin (500 mg each) reached a peak (8.0 micrograms/ml) at 1.5 h after administration, and concentrations were maintained in excess of 1.5 micrograms/ml for 6 h. Serum elimination half-life (1.3 h), volume of distribution (14.5 liters), and area under the curve (AUC; 27.8 micrograms.h/ml) after i.m. injection did not significantly differ from those of a comparable dose given by intravenous infusion. Bioavailability after i.m. injection was 89%. Imipenem levels in skin window fluid after i.m. administration were maximal (4.3 micrograms/ml) at 4 h after injection, at which time imipenem concentrations exceeded those produced by intravenous infusion. The AUCskin window/AUCserum ratio for skin window fluid after i.m. injection was 68%, indicating good penetration of the drug into skin fluid. This study shows that i.m. injection of 500 mg of imipenem-cilastatin results in concentrations of imipenem in serum and skin fluid that are, for at least 6 h, consistent with antimicrobial activity against susceptible organisms. PMID- 1510435 TI - Endotracheal and aerosol administrations of ceftazidime in patients with nosocomial pneumonia: pharmacokinetics and absolute bioavailability. AB - Pharmacokinetic studies on ceftazidime, an aminothiazole cephalosporin with a wide spectrum of antibacterial activity, including activity against Pseudomonas aeruginosa, were performed in patients with nosocomial pneumonia. The concentration-time profiles of ceftazidime in plasma, urine, and bronchial secretions of 12 patients were investigated after intravenous (i.v.) (n = 12), endotracheal (n = 10), and aerosol (n = 5) administrations. In all cases a 1-g dose was administered. Concentrations of drug in all samples were assayed by high performance liquid chromatography with UV detection. The elimination of the drug from the blood followed a biexponential (i.v. administration) or a monoexponential (endotracheal and aerosol administrations) decay, with an elimination half-life of 6 h and a total body clearance of 4.2 liters/h. The apparent volume of distribution was 0.36 liter/kg of body weight. Renal clearance of the drug accounted for 58% of the total clearance; 66% +/- 17.7%, 33.5% +/- 17.3%, and 6.59% +/- 3.45% of the administered dose were eliminated in urine as parent drug after i.v., endotracheal, and aerosol administrations, respectively. The absolute bioavailabilities were 0.47 and 0.08 for endotracheal and aerosol administrations, respectively. Very high concentrations were found in bronchial secretions after local administration. The MICs for 90% of the most important pathogens responsible for nosocomial infections were exceeded by concentrations in bronchial secretion for up to 12 h after i.v. infusion and for up to 24 h after endotracheal and aerosol administrations. PMID- 1510436 TI - In vitro activity and beta-lactamase stability of LJC 10,627. AB - The in vitro activity of LJC 10,627, a new carbapenem, was compared with those of imipenem, cefotaxime, ceftazidime, and gentamicin. LJC 10,627 inhibited 90% of Escherichia coli, Klebsiella pneumoniae, Klebsiella oxytoca, Enterobacter aerogenes, Enterobacter agglomerans, Enterobacter cloacae, Hafnia alvei, Citrobacter freundii, Citrobacter diversus, Proteus mirabilis, Morganella morganii, Proteus rettgeri, Serratia marcescens, Pseudomonas cepacia, salmonellae, shigellae, aeromonas, and yersiniae at less than or equal to 2 micrograms/ml. Haemophilus influenzae was inhibited by 0.5 microgram/ml, and moraxellae were inhibited by 0.12 microgram/ml. LJC 10,627 was twofold more active than imipenem against aerobic gram-negative organisms and inhibited ceftazidime-, cefotaxime-, and gentamicin-resistant members of the genera Klebsiella, Enterobacter, Citrobacter, and Serratia at less than or equal to 2 micrograms/ml. Xanthomonas maltophilia strains were resistant to the drug. Imipenem was two- to fourfold more active than LJC 10,627 against Staphylococcus aureus and Staphylococcus epidermidis. LJC 10,627 did not inhibit most methicillin-resistant Staphylococcus aureus or methicillin-resistant Staphylococcus epidermidis strains. LJC 10,627 inhibited Streptococcus pyogenes and Streptococcus pneumoniae at 0.06 and 0.12 microgram/ml, respectively. Bacteroides fragilis and other Bacteroides spp. were inhibited by 0.5 microgram of LJC 10,627 per ml. Serum (50%) did not affect the MICs. LJC 10,627 was not hydrolyzed by plasmid-mediated beta-lactamases of Bush types 2b, 2b', TEM-1, TEM 2, TEM-3, TEM-5, TEM-7, TEM-9, and SHV-1; the chromosomal beta-lactamases of Bush type 1; P-99; a Morganella enzyme; or a Citrobacter freundii enzyme. The Bush type 2c and 2d enzymes OXA-1, OXA-2, PSE-1, PSE-2, and PSE-4 did not hydrolyze LJC 10,627, nor did the beta-lactamases of Staphylococcus aureus, Moraxella spp., Bacteroides fragilis, and Proteus vulgaris. The beta-lactamase of Xanthomonas hydrolyzed LJC 10,627, albeit at approximately one-third the rate that imipenem was hydrolyzed. PMID- 1510437 TI - Removal of vancomycin by high-flux hemodialysis membranes. AB - Levels of vancomycin in serum are traditionally believed to be unaffected by hemodialysis. By both in vivo and in vitro techniques, the effects of a newer, more permeable dialyzer membrane on vancomycin concentrations were investigated. Six patients who were receiving vancomycin and undergoing maintenance hemodialysis with polyacrylonitrile dialyzer membranes had postdialysis levels in serum that were 63% of predialysis levels; the intradialytic half-life was 5.7 h. Vancomycin concentrations in serum exiting the dialyzer were 68% of those simultaneously entering the dialyzer at the beginning of dialysis. When polyacrylonitrile and conventional cellulose membranes were perfused in vitro with a recirculating solution of vancomycin, vancomycin concentrations fell to 39 and 91%, respectively, of the original concentration. The vancomycin concentration in the ultrafiltrate collected from the polyacrylonitrile membranes was only 23% of the original perfusate concentration. A significant decrease in the serum vancomycin concentration may occur during hemodialysis with newer high flux dialyzer membranes. It appears that vancomycin binds to polyacrylonitrile membranes; this binding does not require the presence of protein and is affected by the pH of the perfusate. PMID- 1510438 TI - Simulation of human serum pharmacokinetics of cefazolin, piperacillin, and BRL 42715 in rats and efficacy against experimental intraperitoneal infections. AB - Studies were performed to determine the effects of BRL 42715, a potent beta lactamase inhibitor, on the activity of cefazolin and piperacillin against experimental intraperitoneal infections caused by either Escherichia coli or Serratia marcescens in rats. Compounds were administered to rats as a continuous infusion of an exponentially diluted solution to simulate in rat plasma the concentration-versus-time curves obtained for humans following intravenous bolus administration. A simulated 1-g dose of cefazolin was ineffective in reducing the bacterial counts in blood and peritoneal fluid samples of animals infected with S. marcescens US20, which produced class Ia beta-lactamase, and as a result, mortality was similar to that of infected controls. Similarly, a simulated 2-g dose of piperacillin was ineffective in reducing bacterial numbers and mortality in animals infected with E. coli 41548, producing a TEM-1 beta-lactamase. However, when the antibiotics were coadministered with BRL 42715, bacterial numbers were reduced significantly and all animals survived at least 16 h after infection. These data demonstrate the ability of BRL 42715 to potentiate the activity of cefazolin and piperacillin against beta-lactamase-producing bacteria that would otherwise be resistant to these antibiotics and illustrate the application of a model to simulate human serum concentrations in conscious rats. PMID- 1510439 TI - Effects of protease inhibitors on replication of various myxoviruses. AB - We studied the effects of eight protease inhibitors on the multicycle replications of various orthomyxoviruses and paramyxoviruses. Among the compounds, nafamostat mesilate, camostat mesilate, gabexate mesilate, and aprotinin, which are widely used in the treatment of pancreatitis, inhibited influenza virus A and B replication at concentrations that were significantly lower than their cytotoxic thresholds in vitro. None of the protease inhibitors had activity against respiratory syncytial virus, measles virus, or parainfluenza virus type 3 at the highest concentrations tested. Camostat mesilate was found to be the most selective inhibitor. Its 50% effective concentration for influenza virus A replication was 2.2 micrograms/ml, and the selectivity index, which was based on the ratio of the 50% inhibitory concentration for host cell proliferation to the 50% effective concentration for influenza virus A replication, was 680. When the in ovo antiviral activity of the compounds was tested by using chicken embryos, camostat mesilate at a dose of 10 micrograms/g markedly reduced the hemagglutinin titers of influenza viruses A and B. PMID- 1510440 TI - Pharmacokinetics of meropenem and its metabolite in young and elderly healthy men. AB - The pharmacokinetics of meropenem and its ring-opened metabolite (ICI 213,689) were investigated with eight young (20- to 34-year-old) and eight elderly (67- to 80-year-old) healthy male volunteers given single 30-min intravenous infusions of 500 mg of meropenem. All subjects had normal age-correlated glomerular function. The mean terminal half-life of meropenem was 1.27 h in the elderly subjects versus 0.81 h in the younger subjects (P less than 0.001). This and similar increases in mean residence time and area under the concentration-time curve were explained by a reduction in total [139 versus 203 ml/(min.1.73 m2); P less than 0.001], renal, and nonrenal clearances in subjects at advanced ages. The apparent volume of distribution and urinary recovery over 8 h were not significantly altered. With the metabolite, prolonged serum half-life and mean residence time, enlarged area under the concentration-time curve, and lower renal clearance but no significant changes in peak plasma concentration or urinary recovery were found in the elderly. The reduction in the renal excretion rate of meropenem and its metabolite corresponds to the age-associated physiological decline in renal function. The capacity to metabolize meropenem may also be slightly impaired in people at advanced ages. Dose reduction of meropenem should be considered for elderly patients. PMID- 1510442 TI - Aerosolized liposomal amphotericin B for treatment of pulmonary and systemic Cryptococcus neoformans infections in mice. AB - Cryptococcus infections of the lung and central nervous system have become major problems in immuno-compromised patients, leading to the need for additional treatment protocols. We have utilized a Cryptococcus-mouse model that mimics human cryptococcal disease to evaluate the efficacy of amphotericin B-liposomes (AmpB-Lip) when delivered by small-particle aerosol (SPA). In the model, initial intranasal inoculation leads to a pulmonary infection that spreads after 2 to 3 weeks to distant organs, including the brain. Aerosols of AmpB-Lip that were generated by a Collison nebulizer had mass median aerodynamic diameters of 1.8 microns and contained 10.3 micrograms of AmpB per liter. When AmpB-Lip SPA was begun at 24 h postinoculation, a single 2-h treatment (0.3 mg of AmpB per kg of body weight) was effective in reducing pulmonary Cryptococcus infection. This regimen was more effective than intravenous administration of AmpB-Lip given for 3 continuous days. This single 2-h exposure to AmpB-Lip also was effective in reducing pulmonary Cryptococcus infection when treatment was delayed for 7 or 14 days. At day 21, when organisms had spread to the brain in all animals, the single 2-h aerosol treatment reduced the number of cryptococci in the brain as well as in the lungs. AmpB-Lip SPA administered once for 2 h on days 7, 14, and 21 also was effective in increasing the duration of survival of infected animals. These results demonstrate that aerosolized AmpB-Lip can be effective in treating both local, pulmonary Cryptococcus disease and systemic disease. PMID- 1510441 TI - Mechanisms of antibacterial action of tachyplesins and polyphemusins, a group of antimicrobial peptides isolated from horseshoe crab hemocytes. AB - Tachyplesins I and II and polyphemusins I and II, cationic peptides isolated from the hemocytes of horseshoe crabs, show bactericidal activities with similar efficiencies for both gram-negative and gram-positive bacteria. Tachyplesin I inhibited bacterial growth irreversibly within 40 min. A subinhibitory concentration of tachyplesin I sensitized gram-negative bacteria to the bactericidal actions of novobiocin and nalidixic acid, although polymyxin B resistant strains which have altered lipopolysaccharides were susceptible to tachyplesin I. This implies that tachyplesin permeabilizes the outer membrane and that the likely target of its action is outer membrane constituents other than lipopolysaccharides. On the other hand, a defensin-susceptible phoP strain of Salmonella typhimurium was also susceptible to tachyplesin I. Tachyplesin I rapidly depolarized the inverted inner-membrane vesicles of Escherichia coli. These results suggest that depolarization of the cytoplasmic membrane, preceded by the permeabilization of the outer membrane for gram-negative bacteria, is associated with tachyplesin-mediated bactericidal activity. The similarity between the actions of tachyplesin and those of defensin was discussed. PMID- 1510443 TI - Preclinical pharmacology and pharmacokinetics of the anti-hepatitis virus agent 2'-fluoro-5-ethyl-1-beta-D-arabinofuranosyluracil in mice and rats. AB - The preclinical pharmacology and pharmacokinetics of 2'-fluoro-5-ethyl-1-beta-D arabinofuranosyluracil (FEAU), a selective inhibitor of herpesvirus and hepatitis virus replication, were investigated in the mouse and rat. Following intravenous (i.v.) or oral (p.o.) administration, FEAU was cleared from the plasma primarily unchanged, with a terminal half-life of 58 to 80 min in the mouse and 63 to 78 min in the rat. The steady-state volumes of distribution times bioavailabilities of FEAU were approximately 2.1 and 3.4 times the total body water volumes after p.o. administration of 10 mg of drug per kg of body weight in mice and rats, respectively. A comparison of the area under the concentration-time curve after i.v. and p.o. FEAU administration indicated that the p.o. dose was completely absorbed in both species. When tritiated FEAU was used in mice, 35.0% of the i.v. dose and 33.5% of the p.o. dose were excreted in urine as unchanged FEAU, 8.1% (i.v. dose) and 9.2% (p.o. dose) were excreted as tritiated water, and 15.6% (i.v. dose) and 18.1% (p.o. dose) were excreted as unknown metabolite(s) in urine within 24 h of dosing. Only 1.24% (i.v. dose) and 2.6% (p.o. dose) of the total doses were found in urine as 3H2O when the FEAU dose was increased to 50 mg/kg. However, a higher percentage of the total dose (59.6% for the i.v. dose and 61.3% for the p.o. dose) was recovered within 24 h as intact FEAU in rat urine, less than 1.4% (i.v. dose) and 2.7% (p.o. dose) of the total dose were found to be 3H2O, and 5.6% (i.v. dose) and 6.7% (p.o. dose) of the total dose were excreted as known metabolite(s). The distribution ratios for total radioactivity in tissue relative to those in plasma were 0.5 to 1.3 in spleen, testes, muscle, and liver during the first hour after a 10-mg/kg dose in rats. Of the total FEAU radioactivity administered, only 1.38% was excreted in bile as unchanged FEAU. No FEAU glucuronide metabolite was detected. Tissue concentrations of 0.15 to 0.6 microM at 6 h after dosing are in the range of the effective antiviral concentration for FEAU. In conclusion, FEAU administered p.o. to mice and rats was well absorbed; FEAU was rapidly distributed into tissues and remained above in vitro antiviral concentrations for more than 6 h; in mice, [3H]FEAU showed metabolism-mediated tritium exchange with water; and in rats, FEAU was less extensively metabolized than in mice and clearance was primarily via renal processes, mainly in the form of unchanged FEAU. PMID- 1510444 TI - Levels of cefmenoxime in sera and peritoneal tissues of patients undergoing gastrointestinal surgery. AB - It is not known whether a prophylactic antibiotic administered prior to surgery reaches adequate levels in the peritoneum, where peritonitis may take place. This study determined levels of cefmenoxime in sera and peritoneal tissues of patients undergoing gastrointestinal surgery. Fifteen patients who underwent elective gastrointestinal surgery received an intravenous drip infusion of cefmenoxime (2 g) over 1 h prior to surgery. In patients who underwent gastrectomy, the level of cefmenoxime in serum was 130.8 +/- 6.9 micrograms/ml at laparatomy and decreased to 5.0 +/- 0.7 micrograms/ml at 4 h. Levels in parietal peritoneal and omental tissues at laparotomy were 35.3 +/- 5.2 and 19.2 +/- 3.5 micrograms, respectively, and decreased time dependently. In patients who underwent cholecystectomy, the level of cefmenoxime in serum was 137.9 +/- 7.3 micrograms/ml at laparotomy and decreased to 5.0 +/- 1.2 micrograms/ml at 4 h. Levels in parietal peritoneal and omental tissues were 31.0 +/- 8.4 and 13.7 +/- 3.3 micrograms/g, respectively, and decreased time dependently. The level of cefmenoxime in serum correlated with the levels of cefmenoxime in parietal peritoneum (r = 0.64, P less than 0.01) and in omentum (r = 0.47, P less than 0.02). In patients with appendicitis who received a bolus injection of 2 g of cefmenoxime, the level of drug in inflammatory omental tissue correlated with the level in serum. The levels in peritoneal tissue during surgery lasting up to 2 h were significantly greater than in MIC of cefmenoxime against almost all bacteria reported. A preoperative single dose of 2 g of cefmenoxime probably is effective as a prophylactic for intraoperative contamination. PMID- 1510445 TI - Analysis of peptidoglycan precursors in vancomycin-resistant enterococci. AB - Analysis by high-pressure liquid chromatography of the cytoplasmic peptidoglycan precursors of a high- and a low-level vancomycin-resistant Enterococcus spp. was performed before and after induction of resistance. This analysis showed a decrease of the D-Ala-D-Ala and UDP-MurNac-pentapeptide pools, an increase of the UDP-MurNac-tripeptide pool, and the appearance of new UDP-MurNac-containing material. These results lead us to suggest that the vancomycin-induced carboxypeptidase activity cleaves the D-Ala-D-Ala (L. Gutmann, D. Billot-Klein, S. Al-Obeid, I. Klare, S. Francoul, E. Collatz, and J. van Heijenoort, Antimicrob. Agents Chemother. 36:77-80, 1992), which in turn would prevent formation of the normal UDP-MurNac-pentapeptide and thereby of the vancomycin target. The novel UDP-MurNac-containing material is thought to correspond to peptidoglycan precursors which might be synthesized by an alternate pathway (T. D. H. Bugg, G. D. Wright, S. Dutka-Malen, M. Arthur, P. Courvalin, and C. T. Walsh, Biochemistry 30:10408-10415, 1991) and which would be unable to bind vancomycin in glycopeptide-resistant enterococci. PMID- 1510446 TI - Comparison of 5 milligrams of netilmicin per kilogram of body weight once daily versus 2 milligrams per kilogram thrice daily for treatment of gram-negative pyelonephritis in children. AB - The efficacy and safety of netilmicin, 5 mg/kg of body weight once daily or 2 mg/kg thrice daily for 10 days, for the treatment of gram-negative pyelonephritis in children were compared in a prospective, randomized trial. Explicit criteria were used to define the site of infection, treatment outcome, and adverse effects. Netilmicin was given to 74 children once daily and to 70 children three times daily. At 1 week posttreatment, 73 (99%) of 74 children treated with netilmicin once daily and 70 (100%) of 70 children treated with netilmicin three times daily were cured. At 4 weeks posttreatment, no relapse was detected and the rate of reinfection was essentially identical in the two treatment groups. Peak serum netilmicin concentrations were higher in patients given the once-daily regimen, whereas a higher trough level was detected in patients given the three times-daily regimen. Nephrotoxicity, which was defined as an increase in the serum creatinine level of greater than or equal to 0.3 mg/dl over the baseline, was rare (3%) and reversible and occurred regardless of the treatment regimen. Ototoxicity, which was assessed by pure-tone audiometry (250 to 8,000 Hz) and brain stem-evoked response (6,000 Hz), occurred in 2 of 32 children who were evaluated. In these two children, who were given the once-daily regimen, wave V was not evokable monolaterally below 25 and 40 dB normal hearing level, respectively. Thus, it may be possible to treat childhood pyelonephritis with netilmicin once daily. However, this new approach needs to be confirmed in other studies. PMID- 1510447 TI - Molecular basis of the non-beta-lactamase-mediated resistance to beta-lactam antibiotics in strains of Haemophilus influenzae isolated in Canada. AB - A study recently conducted across Canada showed that 64 of 2,503 clinical isolates of Haemophilus influenzae were resistant to beta-lactams without production of a beta-lactamase (L. D. Tremblay, J. L'Ecuyer, P. Provencher, M. G. Bergeron, and Canadian Study Group, Can. Med. Assoc. J. 143:895-900, 1990). The beta-lactamase-negative strains formed three distinct groups, with ampicillin MICs of 0.5 to 1, 2 to 4, and greater than or equal to 8 micrograms/ml for groups I, II, and III, respectively. We have investigated the mechanisms of resistance for eight strains originating from different infections and geographic areas. These strains were representative of groups I to III. Five strains were nontypeable, two were type B, and one was non-B. Chromosomal DNA extracted from each strain was used to transform the laboratory strain Rd. Transformants were selected on beta-lactam-containing plates and showed the same level of resistance to ampicillin as the donor strains. Differences in outer membrane proteins, porins, and lipopolysaccharide profiles on sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) did not change with resistance. Functional analyses of purified porins in artificial lipid bilayer experiments did not explain resistance. Peptidoglycan synthesis was measured by incorporation of [14C]alanine into trichloroacetic acid-insoluble cell wall material in the presence of chloramphenicol. The growth rate and the rate of peptidoglycan synthesis observed for the transformants of the isogenic set did not correlate with resistance. Whole-cell labeling with 125I-penicillin revealed modifications in penicillin-binding proteins (PBPs) among the transformants. In particular, PBPs 3A and 3B (65 and 63 kDa, respectively) showed a decrease in affinity for beta-lactams in all transformants (groups I, II, and III) and correlated with an increased MIC except in the transformant of group III, which showed higher levels of resistance. Partial purification and proteolytic digestion of 125I-penicillin labeled PBP 3B led to two types of CnBr peptide profiles on SDS-PAGE, the profiles of the transformed strains from groups I and II being different from those of the control group and group III. Finally, electron microscopy revealed a distinct cell filamentation for the group III transformants. These data clearly indicate that changes in PBPs are a common mechanism that results in a significant level of non-beta-lactamase-mediated beta-lactam resistance in H. influenzae despite serotype, origin of isolation, or geographic distribution. PMID- 1510448 TI - Characterization of vanY, a DD-carboxypeptidase from vancomycin-resistant Enterococcus faecium BM4147. AB - VanY is a protein with a molecular mass of 34.8 kDa encoded by vanY, a member of the high-level vancomycin resistance gene cluster found on plasmid pIP816 in Enterococcus faecium BM4147. Extracts from Escherichia coli JM83 bearing plasmid pAT383, which contains the vanY gene, were examined for enzymatic hydrolysis of peptidoglycan precursors. VanY was associated with the cell membranes and cleaved the C-terminal D-alanine residue of UDP-muramyl-pentapeptide but did not display transpeptidase or beta-lactamase activities. The DD-carboxypeptidase activity was not inhibited by beta-lactam antibiotics. VanY released the C-terminal D-hydroxy acid from depsipeptides produced by the vancomycin resistance protein VanA. These results demonstrate that VanY should contribute in vivo to the hydrolysis of both the D-alanyl-D-alanine- and the depsipeptide-containing peptidoglycan precursors. PMID- 1510449 TI - Didanosine pharmacokinetics in patients with normal and impaired renal function: influence of hemodialysis. AB - The pharmacokinetics of didanosine were investigated following oral administration of a single 375-mg dose to eight human immunodeficiency virus seropositive patients with normal renal function and eight human immunodeficiency virus-seropositive uremic patients. In uremic patients, the plasma half-life was longer than that in control patients (respectively, 4.5 +/- 2.2 and 1.6 +/- 0.4 h). The ratio of total plasma clearance to absolute bioavailability was four- to fivefold lower in uremic patients than in patients with normal renal function (respectively, 491 +/- 181 and 2,277 +/- 738 ml/min). Because of the decrease in elimination, concentrations in plasma were higher for uremic patients than for control patients; the maximum concentrations of drug in plasma were, respectively, 3,978 +/- 1,607 and 1,948 +/- 994 ng/ml; the areas under the concentration-time curve were, respectively, 14,050 +/- 4,262 and 3,000 +/- 956 ng.h/ml. Didanosine was removed by hemodialysis with an extraction ratio of 53% +/- 8%, a hemodialysis clearance value of 107 +/- 21 ml/min, and a fractional drug removal during a 4-h dialysis of 20% +/- 8% of the dose. Dosage adjustments are necessary in uremic patients. PMID- 1510451 TI - Pharmacokinetics of meropenem in subjects with various degrees of renal impairment. AB - Five healthy volunteers and 18 patients with various degrees of renal impairment received 500 mg of meropenem intravenously as a 30-min infusion. Five dialysis patients were dosed 2 h prior to hemodialysis, and four of them were also dosed between hemodialysis treatments. Plasma and urine samples were collected for up to 48 h and 12 h, respectively. Concentrations of meropenem and its open ring metabolite ICI 213,689 were determined by high-performance liquid chromatography and radioimmunoassay, respectively. The subjects were divided into four groups with glomerular filtration rates (GFR) of greater than 80, 30 to 80, 5 to 29, or less than 5 ml/min. There were linear correlations between the GFR and the rates for total plasma clearance as well as renal clearance of meropenem (group mean values for total clearance of 186, 74, 53, and 19 ml/min/1.73 m2, respectively). In subjects with normal renal function, nonrenal clearance accounted for approximately 20% of total elimination, increasing to about 50% in patients with GFR between 5 and 29 ml/min/1.73 m2. The terminal half-life of meropenem increased from 0.9 h in the healthy volunteers to 6.8 h in patients with end stage renal disease. The half-life of ICI 213,689 was 2.31 h in the healthy volunteers and increased to 23.6 h in patients with GFR of 5 to 29 ml/min. In patients with end-stage renal disease, half-lives could not be measured, as concentrations were hardly declining during the 48-h observation period. The area under the concentration-time curve for meropenem increased more than 10-fold. Both meropenem and its open ring metabolite were readily dialyzable, with dialysis clearances of 79 and 81 ml/min/1.73 m2, respectively. PMID- 1510450 TI - Comparison of nephrotoxicities of different polyoxyethyleneglycol formulations of amphotericin B in rats. AB - The aim of the present study was to assess whether amphotericin B (AmB)-Myrj 59, AmB-polyoxyethyleneglycol 24 cholesterol (PC), and AmB-Synperonic A50 (SA50) were less nephrotoxic than AmB-deoxycholate (DC). Rats were treated with the different AmB formulations (10 mg/kg of body weight) intraperitoneally or with the surfactants alone. A group of control rats receiving the vehicle was also examined. After 6 days of daily intraperitoneal injections of AmB-DC, decreased body weight and glomerular filtration rate as well as increased degree of diuresis, uremia, microalbuminuria, and N-acetyl-beta-D-glucosaminidase excretion in urine were noted. Urinary excretion of potassium and sodium was also decreased in AmB-DC-treated rats. Most of these effects were more pronounced with AmB-PC and AmB-SA50. In contrast, AmB-Myrj 59 was less nephrotoxic than AmB-DC. Indeed, after 6 days of treatment with AmB-Myrj 59, the natriuria, kaliuria, albuminuria, and glomerular filtration rates were unchanged compared with those of controls. Moreover, the body weight loss and uremia increase of the rats treated by AmB Myrj 59 were less than those of the rats treated with the commercial preparation. Among the surfactants, only PC was toxic for the rats. The intrinsic toxicity of PC and the higher systemic exposure to AmB could contribute to increased toxicities of AmB-PC and AmB-SA50, respectively. AmB-Myrj 59 was less nephrotoxic than AmB-DC at equivalent areas under the plasma concentration-time curves. These preliminary results suggest that this formulation could be a good alternative to the commercial product. PMID- 1510452 TI - Stereochemical evaluation of the relative activities of the cinchona alkaloids against Plasmodium falciparum. AB - Quinine and quinidine were over 100 times more active than 9-epiquinine and 9 epiquinidine against chloroquine-sensitive Plasmodium falciparum and over 10 times more active against chloroquine-resistant P. falciparum. Since the only structural difference between quinine, quinidine, 9-epiquinine, and 9 epiquinidine is their three-dimensional configuration, the three-dimensional structures of these four alkaloids were examined in order to explain the large difference in relative activities between the 9-epi alkaloids and quinine and quinidine. The crystal structure of 9-epiquinidine hydrochloride monohydrate was determined by X-ray diffraction and was compared with the crystal structures of quinine, quinidine sulfate dihydrate, and 9-epiquinine hydrochloride dihydrate. The crystallographic parameters for 9-epiquinidine hydrochloride monohydrate were as follows: chemical formula, C20H25N2O2+.Cl-.H2O; M(r), 378.9; symmetry of unit cell, orthorhombic; space group, P2(1)2(1)2(1); parameters of unit cell, a was 7.042 +/- 0.001 A (1 A = 0.1 nm), b was 9.082 +/- 0.001 A, c was 31.007 +/- 0.005 A; the volume of unit cell was 1,983.1 +/- 0.6 A3; number of molecules per unit cell was 4; the calculated density was 1.27 g cm-3; the source of radiation was Cu K alpha (lambda = 1.54178 A); mu (absorption coefficient) was 18.82 cm-1; F(000) (sum of atomic scattering factors at zero scattering angle) was 808; room temperature was used; final R (residual index) was 5.72% for 1,501 reflections with magnitude of F(o) greater than 3 sigma (F). The intramolecular distance from N-1 to O-12 in 9-epiquinidine and 9-epiquinine, although shorter than the corresponding distance in quinine and quinidine, was similar to those of other active amino alcohol antimalarial agents. In all four alkaloids, both the hydroxyl and amine groups formed intermolecular hydrogen bonds, showing the potential for forming hydrogen bonds with cellular constituents. However, the positioning of the N+-1--H-N1 and O-12--H-O12 groups relative to each other was quite different in the 9-epi alkaloids versus quinidine. This difference in positioning may determine the relative strengths, of the formation of hydrogen bonds with cellular constituents important to antimalarial activity and, therefore, may determine the relative strength of antimalarial activity. PMID- 1510453 TI - Use of an enzyme-linked immunosorbent assay to assess penetration of amoxicillin into lung secretions. AB - An enzyme-linked immunosorbent assay (ELISA) was developed to measure total amoxicillin concentrations penetrating lung secretions, which were compared with "active" concentrations measured by conventional bioassay. An antibody was raised in rabbits to amoxicillin conjugated to bovine serum albumin and used in a competitive binding ELISA (sensitivity, 10 ng/ml; precision [coefficient of variation], 9%). The measurement of amoxicillin in lung secretions by using the ELISA method was verified by high-performance liquid chromatography. Amoxicillin concentrations were found to be similar in both whole sonicated sputum and sol phase sputum obtained by ultracentrifugation following single oral doses of 3 g (4.6 mg/liter for sonicated and 4.7 mg/liter for sol-phase preparations) and 250 mg (0.23 mg/liter for both preparations). Eight patients with bronchiectasis received 500 mg of amoxicillin three times daily. On the second day of therapy (4 h after the morning dose), the mean concentration of amoxicillin in sputum was 0.88 mg/liter (standard error of the mean [SEM], 0.11) by ELISA and 0.40 mg/liter (SEM, 0.05) by bioassay, suggesting a significant degree of local inactivation. This difference between total and active amoxicillin levels was found to correlate significantly (r = 0.693; P less than 0.05) with beta-lactamase levels (mean, 29.5 mU/ml; SEM, 9.4). A pharmacokinetic study on day 3 revealed maximum levels in secretions 2 to 4 h after dosing (mean, 1.36 mg/liter; SEM, 0.26). At the end of successful therapy (day 14), total and active levels were lower (mean, 0.48 mg/liter; SEM, 0.11 [total]; mean, 0.21 mg/liter; SEM, 0.06 [active]); this result was associated with a reduction in lung inflammation (decreased serum derived albumin in the lung secretions). In conclusion, antibiotic penetration is partly dependent on the degree of lung inflammation. The differences observed in total and active levels of amoxicillin and the relationship to beta-lactamase activity in sputum suggest why higher doses of antibiotic may be required to produce a therapeutic response in some patients. PMID- 1510455 TI - Inconsistent bactericidal activity of triple-combination therapy with vancomycin, ampicillin, and gentamicin against vancomycin-resistant, highly ampicillin resistant Enterococcus faecium. AB - Combination therapy with ampicillin, vancomycin, and gentamicin in vitro against several clinical isolates of vancomycin-resistant, highly ampicillin-resistant Enterococcus faecium, including VanA and VanB strains, was evaluated. The MICs of ampicillin were not significantly decreased by induction with vancomycin, and the combination of ampicillin and vancomycin was not inhibitory for any strain. Triple-combination therapy was least active against highly resistant VanA isolates, achieving a reduction of less than 1 log CFU at 24 h, but demonstrated slightly more activity against VanB strains. PMID- 1510456 TI - Intraocular penetration of rifampin in humans. AB - The penetration of rifampin into human aqueous humor was determined in 15 patients undergoing elective cataract surgery. Between 0.9 and 5.5 h after administration of a single 600-mg oral dose, concentrations ranged from 6.0 to 21.5 mg/liter in serum and from less than 0.2 to 1.3 mg/liter in aqueous humor. PMID- 1510454 TI - Two- and four-day rifampin chemoprophylaxis regimens induce oxidative metabolism. AB - The effects of two short-term chemoprophylaxis regimens of rifampin (2 or 4 days) on oxidative metabolism were investigated in 14 healthy subjects. Seven subjects received 600 mg of rifampin twice daily on study days 6 and 7 (group A), and seven subjects received 600 mg of rifampin once daily on days 4, 5, 6, and 7 (group B). Antipyrine (18 mg/kg of body weight) was administered orally on days 1, 8, and 15. Short-term rifampin regimens increased oral clearance of antipyrine in both groups compared with the baseline value (P less than 0.05), and group B displayed a larger percent increase over the baseline value than group A did (70.5 +/- 14.3 versus 33.1 +/- 18.1; P less than 0.05). The partial metabolic clearance (CLM) of antipyrine to 3-hydroxymethylantipyrine (HMA) on day 8 increased 71 and 108% for regimens A and B, respectively (P less than 0.05 for both). The corresponding increases in CLM to norantipyrine (NORA) were 57 and 98% (P less than 0.05 for both). CLM to 4-hydroxyantipyrine (OHA) on day 8 increased 64% for regimen A (P = 0.08) and 97% for regimen B (P less than 0.05) compared with the baseline. Although CLM to HMA and OHA on day 15 remained greater than 50% over the baseline with both regimens, CLM to NORA on day 15 was less than 25% over the baseline with both regimens. Thus, both short-term rifampin chemoprophylaxis regimens increased antipyrine clearance for at least 1 week. The increase tended to be higher with the 4-day regimen. The pattern observed for the CLMS suggests that more than one P-450 enzyme is affected. PMID- 1510458 TI - Evaluation of the usefulness of a novel injectable cephalosporin, E1040, and ceftazidime for management of complicated urinary tract infections caused by Pseudomonas aeruginosa and Proteus mirabilis by using the rat urolithiasis model. AB - A novel injectable cephalosporin, E1040, significantly eradicated Pseudomonas aeruginosa from the urine, in contrast to ceftazidime, in rats with complicated P. aeruginosa urinary tract infections associated with urinary stones, suggesting that E1040 is a prospective therapeutic agent in the management of refractory Pseudomonas urinary tract infections. PMID- 1510457 TI - Stability of meropenem and effect of 1 beta-methyl substitution on its stability in the presence of renal dehydropeptidase I. AB - The stability of meropenem in the presence of renal dehydropeptidase I (DHP-I) varied extremely with the animal source of the enzyme. Meropenem, compared with imipenem, was rather easily hydrolyzed by DHP-Is from mice, rabbits, and monkeys, while it showed a higher resistance to guinea pig and beagle dog DHP-Is. In addition, meropenem was four times more resistant than imipenem to human DHP-I. The 1 beta-methyl substituent on carbapenems, i.e., meropenem and 1 beta-methyl imipenem, made them considerably more resistant to mouse and swine DHP-Is than the 1-unsubstituted derivatives are. PMID- 1510459 TI - Ticarcillin-clavulanic acid dosing ratio for treatment of experimental Staphylococcus aureus endocarditis. PMID- 1510460 TI - Detecting methicillin resistance in Staphylococcus aureus by polymerase chain reaction. PMID- 1510461 TI - Eating style and eating behaviour in adolescents. AB - The relationship between eating style, attitudes towards food and food intake was investigated in 846 British adolescent schoolchildren. Eating style was assessed with the Dutch Eating Behaviour Questionnaire, attitudes towards food with a series of specially prepared questions, and food intake with a diet history taken by a dietitian. The results showed that restraint, external and emotional eating were associated with very different profiles of attitudes and behaviour. Restrained subjects had a higher body weight, more negative attitudes towards food, a lower likelihood of overeating and a lower overall energy intake. External eaters had a lower body weight, positive attitudes to food, and reported a higher energy intake. Emotional eaters fell in between in some ways, with some signs of situational loss of control combined with a negative attitude towards overeating. While external eating appeared to be attenuated by restraint, emotional eating was enhanced by it. The implications of these eating styles for later patterns of eating and weight are discussed. PMID- 1510462 TI - Perceptions of spreading fats among women in Helsinki whose households use only butter or margarine. AB - This study sought to investigate whether women's perceptions about butter and soft margarine vary by the use of these fats. From interviews in 1984 with 102 middle-aged women from a follow-up dietary survey in Helsinki 27% of their households were classified as exclusive butter users, 46% used both butter and margarine and 27% used only margarine. The women evaluated margarine less "tasty" but "lighter", and "healthier" than butter. Women whose households used butter exclusively rated it more "useful" than those who used margarine, whereas women whose households used exclusively margarine rated it higher on taste than did exclusive butter users. Butter is a valued traditional food in Finland, and probably the taste of butter is still a reference standard for all spreads. Nevertheless some of the respondents had evidently come to like the soft vegetable margarine that was not available in their childhood. PMID- 1510463 TI - Food preferences in human obesity: carbohydrates versus fats. AB - A large clinical sample of obese men and women were asked for a self-generated list of ten favorite foods. The lists were characterized by frequent instances of foods that are major nutrient sources of fat in the American diet. While obese men listed mainly protein/fat sources (meat dishes) among their favorite foods, obese women tended to list predominantly carbohydrate/fat sources (doughnuts, cookies, cake) and foods that were sweet. There was no evidence that selective preferences for a single macronutrient, carbohydrate, were a standard feature of human obesity. Rather, preferences for major nutrient sources of fat as opposed to carbohydrate may be a primary characteristic of human obesity syndromes. PMID- 1510464 TI - Experience with a macronutrient source influences subsequent macronutrient selection. AB - We examined the influence of experience with a macronutrient on subsequent macronutrient selection. For 4 days, rats ate chow, or chow and a single macronutrient source. They then had simultaneous access to protein, carbohydrate (CHO) and fat sources, according to a standard macronutrient self-selection paradigm. When selecting among the macronutrient sources, rats pre-exposed to CHO ate more CHO, and those pre-exposed to fat ate more fat, relative to the other groups. Rats pre-exposed to protein ate more protein than did those pre-exposed to CHO or fat but not more than those that received no macronutrient pre exposure. These selection patterns persisted for at least 12 days, when the test was ended because of the low protein intakes and poor growth of the rats pre exposed to the CHO and fat sources. After 34 days of recovery with only chow to eat, the rats were again allowed to choose among the three macronutrients, and their patterns of selection were essentially unchanged. Similar results were found in a second experiment in which a 5-day interval was interposed between macronutrient pre-exposure and macronutrient selection. These findings show that experience with the macronutrients typically used in self-selection experiments can have a large, long-lasting, and sometimes detrimental effect on subsequent food selection by rats. Prior experience can be a more powerful influence than nutritional wisdom in determining the rat's food choice. PMID- 1510465 TI - Behavioral assessment of satiety in bulimia nervosa. AB - The abnormalities in eating behavior associated with bulimia nervosa suggest that patients with this illness may have a disturbance in satiety. The present study employed a six-meal protocol to assess satiety in both binge and non-binge eating episodes in women with bulimia nervosa and normal controls by examining whether an increase in the size of a soup preload led to a decrease in the amount of food consumed in a subsequent test meal. In control subjects, the increase in preload size was associated with an increase in fullness and a reduction in consumption of the non-binge test meal. Patients did not report consistent changes in ratings of hunger and fullness in response to the change in preload size, and few patients were able to complete the non-binge meals and refrain from vomiting afterwards. When instructed to binge eat, patients ate considerably more than control subjects, but patients did significantly reduce their intake of the test meal after the large compared to the small preload. These findings demonstrate that, although patients with bulimia nervosa exhibit abnormalities in the development of satiety, some mechanisms responsible for the control of food intake are functional during binge eating episodes. PMID- 1510466 TI - Integrated metabolic control of food intake. PMID- 1510467 TI - Human hunger: is there a role for blood glucose dynamics? PMID- 1510468 TI - Amperometric enzyme sensor for glucose based on graphite paste-modified electrodes. AB - Amperometric enzyme electrode for glucose is described based on the incorporation of glucose oxidase (GOD) into graphite paste modified with tetracyanoquinodimethane (TCNQ). The incorporated enzyme exhibits high activity and long-term stability over the earlier TCNQ-based glucose sensor (1). The sensor provides a linear response to glucose over a wide concentration range. The response time of the sensor is 15-50 sec, and the detection limit is 0.5 mM. Stable response to the substrate was obtained during a period of 35 d. Application of the sensor in the plasma analysis is reported. PMID- 1510469 TI - Obtaining mutants for protoplast fusion of gibberellin-forming Gibberella fujikuroi strains. AB - Auxotrophic, drug-resistant, nitrate-nonutilizing, and albino mutants have been isolated in Gibberella fujikuroi following UV mutagenesis. Protoplasts of complementing auxotrophic strains, mutants with resistance markers, or mutants blocked in different steps of the nitrate assimilatory pathway have been fused to form heterokaryons, diploids, or recombinant haploids. The properties of fusant strains, including gibberellic acid productivity, have been examined and compared to parent strains. PMID- 1510470 TI - [Can one foresee the future of urologic surgery?]. PMID- 1510471 TI - [Wunderlich syndrome secondary to the rupture of an aneurysm of the renal artery. Review of the literature]. AB - We report a case of Wunderlich's syndrome secondary to spontaneous rupture of a renal artery aneurysm. Wunderlich's syndrome, also called spontaneous perirenal hematoma, may arise from several causes, the most common being renal tumors, particularly angiomyolipoma and hypernephroma. Spontaneous perirenal hematoma secondary to a ruptured renal artery aneurysm is rare and very few cases have been reported in the literature. We discuss the usefulness of the different noninvasive imaging techniques (US, CT and arteriography), our therapeutic approach and those advocated by others. PMID- 1510473 TI - [Does the surgical approach used for radical nephrectomy change the prognosis of renal carcinoma?]. AB - To determine the influence of the surgical approach on survival, we conducted a retrospective study in 133 patients with renal carcinoma stage T1-T3 N0 M0 (UICC classification, 1987) submitted to radical nephrectomy. Overall no significant difference was observed in the 5 and 10-year survival rates for the different approaches (lumbotomy, transperitoneal laparotomy and thoracophrenolaparotomy). The 10-year survival rate for the cases with tumor stage T1-T2 varied significantly according to the approach: Thoracoabdominal (100%), lumbotomy (60%) and laparotomy (40%). No difference was observed for those with tumor stage T3a. For T3b the survival rate was higher for the lumbotomy approach and a significant difference was observed versus thoracophrenolaparotomy. The results show that the surgical approach does not influence the prognosis of renal carcinoma and choice depends on tumor size, location and invasion of the renal vein and/or vena cava. PMID- 1510472 TI - [Nephrogenic adenoma of the upper and lower urinary tract. Apropos of 22 cases]. AB - Nephrogenic adenoma (NA) is a lesion that can present in the urothelium--from the renal pelvis to the urethra-, and is considered to be immature metaplasia arising from chronic aggression. We report 22 cases of NA in 21 patients that had been diagnosed and treated in our service from 1975 to 1990. The lesion was found at all levels of the urinary tract: renal pelvis (1 case), ureter (1 case), bladder (16 cases) and urethra (4 cases). The present series was comprised of 15 males (one with bladder NA and recurrence in urethra) and 6 females, with ages ranging from 24 to 79 years (mean 55). The diagnosis was made on the histological findings in all cases and the etiology of the lesion was multiple: previous surgery (11 cases), previous or coexisting urothelial carcinoma (8 cases), intracavitary chemotherapy and/or pelvic radiotherapy (3 cases), previous history of tuberculosis (5 cases), interstitial cystopathy (4 cases), lithiasis (2 cases), permanent catheter (3 cases) and urethral stenosis (1 case). Treatment and prognosis was influenced by the underlying urological disease. NA per se does not carry an unfavourable prognosis. PMID- 1510474 TI - [Cystine calculi: x-ray diffraction study. Infrared spectroscopy and SEM]. AB - The present study investigated cystinuria and cystine calculi. Inexplicably, of 987 calculi that had been analyzed ultrastructurally at the Department of Urology of the University Hospital of Salamanca over a period of 15 years only 3 (0.3%) were cystine. The foregoing finding does not coincide with the 0.5-1% incidence reported in the world literature. Apart from the chemical analyses, infrared spectroscopy disclosed the typical findings of multiple bands 1600-625 cm-1. Analysis by x-ray diffraction revealed a slight variation from the ASTM values. One of the calculi, which we considered to be a mixed calculus (probably of calcium phosphate), showed a peak at 43 degrees, instead of the usual 34.5. Scanning electron microscopy disclosed two forms of crystallization: The typical hexagonal form of cystine stones and the rectangular form of different sizes. The material comprising the matrix was observed in many areas, covering and joining the crystals as if it were cement. Whenever possible, treatment of these recurrent calculi should be conservative. Some advocate the use of ESWL, although others consider these calculi to be extremely hard and, therefore, not amenable to ESWL. Chemical dissolution is advocated by some, although its critics consider it to be of little use. Concerning prophylaxis, forced fluids and alkalinization may reduce recurrence. Ultrastructural studies have provided further insight into the structure and composition of cystine calculi. The foregoing may be useful in determining the most appropriate form of treatment based upon stone size, shape, composition (pure or mixed), etc. PMID- 1510475 TI - [Treatment and evolution of 100 cases with staghorn lithiasis]. AB - We reviewed 100 selected cases of staghorn stone that have been followed for at least 3 years after treatment. The results achieved by surgery (e.g., intrasinusal pyelolithotomy) and non-surgical treatment (e.g., ion exchanger) are presented. Overall, good results were achieved in 57% of the cases. PMID- 1510476 TI - [New classification of vesicoureteral reflux]. AB - Five illustrative cases of vesicoureteral reflux, of different age and sex, are described. All patients were submitted to urodynamic evaluation. A new classification based on the underlying cause is purported. Ureterovesical reflux may be passive or active. The latter type may be involuntary, voluntary or caused by abdominal pressure. In our view, this new classification could be useful in the management of vesicoureteral reflux. PMID- 1510477 TI - [Pyeloureteral junction syndrome. Associated vesicoureteral reflux]. AB - We reviewed our series comprised of 106 children that had undergone surgery for congenital hydronephrosis from ureteropelvic junction obstruction. Following our protocol, all patients were evaluated by serial micturition cystourethrography. The only anomaly that had been detected was vesicoureteral reflux in 11.32% of the cases. This incidence is reduced to 8.25% if only the renoureteral systems with both congenital anomalies are considered. This finding is not statistically significant (p less than 0.05) relative to patient age, sex or clinical symptoms. The results of the present study show that children with ureteropelvic junction obstruction are not at risk of developing vesicoureteral reflux. Thus, routine serial micturition cystourethrography appears to be unwarranted. PMID- 1510478 TI - [Surgical correction of congenital penile curvatures using the Nesbit technique. Apropos of 24 cases]. AB - We present our experience of 24 cases with congenital penile deviation without hypospadias. Treatment was by surgical correction of the curvature using the Nesbit technique. We briefly describe the diagnostic methods and the parameters utilized for surgical planning and evaluation of the results of surgery. This simple procedure achieved good results in all of our cases. PMID- 1510479 TI - [Lymphatic involvement predominating and revealing prostatic carcinoma]. AB - The lymphatic system is the most common site of metastasis of prostatic carcinoma. However, carcinoma of the prostate presenting as lymphadenopathy is rare. It can present at any site and may sometimes mimic lymphoreticular tumors. The diagnosis is based on the histological findings. Histochemical techniques using immunoperoxidase demonstration of acid phosphatase and prostate specific antigen are fundamental in detecting the occult tumor of the prostate. Treatment is palliative and enlargement may occasionally remit with hormone therapy. The prognosis is invariably poor. Survival is less than 5 years irrespective of the response to treatment. Three cases are described herein: 2 presented as retroperitoneal mass and 1 as left lateral cervical lymphadenopathy. PMID- 1510480 TI - [Pure squamous carcinoma of the ureter. Review of a case]. AB - We report a case of squamous cell carcinoma of the ureter with periureteral infiltration. Three years following radical surgery, no evidence of tumor progression has been observed. Only 1% to 1.6% of urothelial tumors of the upper urinary tract are purely squamous cell tumors. This tumor type carries a poor prognosis. Currently, the best results can be achieved by early diagnosis and radical surgery. PMID- 1510481 TI - [Polycythemia as the first and only manifestation of renal adenocarcinoma]. AB - We report on a 40-year-old patient with adenocarcinoma of the right kidney whose first and only manifestation was the erythrocytosis that had been detected on routine analytical work up. The diagnostic methods (US, IVP, CT, aspiration biopsy cytology and renal arteriography) and treatment (right nephrectomy via extended thoracophrenolaparotomy incision at the level of the ninth rib) are briefly described. The polycythemia remitted following nephrectomy. The etiopathogenesis and hypotheses that have been put forward relative to polycythemia in renal adenocarcinoma are briefly discussed. Renal tumor, particularly renal adenocarcinoma, should be suspected in the presence of polycythemia of unknown origin. Persistent or recurrent polycythemia should prompt us to suspect incomplete tumor excision or metastasis. Surgical risks (embolism, hemorrhage, etc.) may be reduced if hematocrit levels are brought down to within normal levels by bleeding. PMID- 1510482 TI - [Leiomyoma of the renal capsule. Presentation of a case and review of the literature]. AB - Leiomyoma of the renal capsule is rare and very difficult to diagnose preoperatively. We report on a patient in whom a solid renal mass had been incidentally detected during ultrasound evaluation for a gastroenterological condition. A CT scan confirmed the presence of a solid mass. The intraoperative biopsy showed it was a benign tumor and conservative surgery was performed. According to the literature, this tumor type has, as yet, not been diagnosed preoperatively. However, some angiographic features may indicate the presence of this condition. This is the fourth case of leiomyoma of the renal capsule reported in the literature and the second case treated by conservative surgery. PMID- 1510483 TI - [Primary malignant tumor of the ureter. Presentation of a case]. AB - Herein we report a case of malignant primary tumor of the ureter that had been seen and treated in the Department of Urology of Hospital Docente Clinico Quirurgico "10 de Octubre", in Havana, Cuba. The incidence, possible etiology, classification, forms of presentation, diagnosis, treatment and prognosis of this disease entity are discussed. The national and the world literature are reviewed. PMID- 1510484 TI - [Rhabdomyosarcoma of the epididymis]. AB - A 5-year-old boy with intrascrotal rhabdomyosarcoma arising from the epididymis is described. The patient was submitted to radical orchidectomy via the inguinal approach and high ligation of the spermatic cord. The anatomopathological examination revealed germ cell rhabdomyosarcoma of the epididymis with no testicular or spermatic cord involvement, which corresponded to stage I of the IRS classification (Intergroup Rhabdomyosarcoma Study). Its clinical and histological features and treatment are discussed. PMID- 1510485 TI - Phase I-II pilot study on the efficacy and tolerability of neoadjuvant chemotherapy (Rescue M-VEC) and preoperative radiation therapy for infiltrating bladder cancer: results of an 18-month follow-up. AB - In spite of the improvement of surgical techniques used alone or in combination with preoperative radiation therapy, more than 50% of the patients with infiltrating transitional cell carcinoma (TCC) of the bladder die of distant metastases. Systemic antiblastic polychemotherapy has been reported to achieve a complete remission rate of approximately 30% in patients with infiltrating bladder TCC, although there are still doubts relative to the duration of such complete remissions. This study investigated the efficacy and tolerability of a preoperative chemo- and radiotherapeutic treatment modality and the possibility of performing preservative surgery. Thirty-seven patients with bladder TCC stage T2-T4, N0, M0, have been subjected to neoadjuvant chemotherapy according to the "Rescue M-VEC" scheme of methotrexate 30 mg/m2 +folinic acid 15 mg. after 24 hours on days 1, 15, 22; vinblastine 3 mg/m2 on days 1, 15, 22; epidoxorubicin 30 mg/m2 on day 1 and cisplatin 70 mg/m2 on day 1. The course was repeated from day 29. After 2 "Rescue M-VEC" courses, the patients received pelvic cobalt tele therapy (CTT) combined with cisplatin 24 mg/m2/week. The patients were then restaged. Those with complete remission (CR) received consolidation radiotherapeutic boost combined with cisplatin 24 mg/m2/week, avoiding radical cystectomy. Such treatment was also given to patients with significant partial remission (PR) who had undergone TUR or partial cystectomy. In all the remaining cases we carried out radical cystectomy. We obtained 45.7% CR, 31.4% PR and 22.8% were non-responders (NR), of 35 patients who were evaluable at restaging. Only 9 radical cystectomies were performed in this series. The overall survival rate was 80.6% at a mean follow-up of 18.1 months.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1510486 TI - [Has endourology reached its limits?]. PMID- 1510487 TI - [Retroperitoneal abscess: analysis of 26 cases]. AB - Herein we present the experience of our hospital, which spans a period of 10 years, in the diagnosis and treatment of retroperitoneal abscess. The clinical features, origin and localization of the abscesses are described. We underscore the diagnostic value of ultrasound (US) and computerized tomography (CT) which afford a sensitivity of 86.3% and 100%, respectively. An increased incidence of abscess from gram-positive bacteria was observed in i.v. drug addicts. PMID- 1510488 TI - [Fournier's gangrene. Report of 6 cases]. AB - Fournier's gangrene is an uncommon pathological condition that affects the perineoscrotal region. Its course is fulminant and it carries a high mortality. We present 6 cases that had been treated over a period of 24 months. The mortality rate was 33.3%. The mean patient age was 53 years. The clinical and therapeutic aspects are discussed. The need to perform wide repeated debridement and the usefulness of the epidural catheter are underscored. PMID- 1510489 TI - [Prophylaxis in prostatic surgery with aztreonam. Our experience]. AB - Aztreonam is a monobactam antibiotic with a very specific spectrum of action for gram-negative aerobic bacteria. Since these bacteria are responsible for most of the urinary tract infections, we conducted a study to determine its efficacy in the prophylaxis and treatment of infections in prostate surgery, one of the most common procedures performed in our field. Thirty-two patients received 1 gm Aztreonam at the time of anesthetic induction and q 8 h thereafter to a total dose of 3 gm. Cultures were performed before and 72 h after surgery. Twenty-eight patients had no complications and a sterile urine culture or less than 10,000 colonies, 2 developed wound infection from Staph, aureus and 1 had more than 100,000 colonies of Enterococci in urine. The foregoing findings indicate that Aztreonam is useful for prophylaxis and treatment of urinary tract infections in prostate surgery. PMID- 1510490 TI - [Incidence of urothelial carcinoma of the bladder in males with chronic urinary retention]. AB - The author studied all of the 1361 male patients that had been hospitalized from December 1986 to September 1990 for chronic urinary retention to determine the incidence of urothelial tumor of the bladder. Sixty-nine (5.07%) were found to have primary urothelial carcinoma of the bladder. However, in another study group comprised of 433 males over 55 with no problems of obstruction, 0.23% had a bladder tumor. This study underscores the role of urinary stasis in the development of urothelial carcinoma of the bladder. PMID- 1510491 TI - [Simultaneous presentation of bilateral renal adenocarcinoma. Therapeutic possibilities]. AB - Bilateral renal adenocarcinoma accounts for 1.4% to 5% of all renal adenocarcinomas. Currently, an increased incidence of synchronous bilateral renal adenocarcinoma has been observed, which can be ascribed to the availability of more sophisticated high resolution ultrasound and computed tomography. Several surgical options exist, such as bilateral radical resection, radical surgery combined with partial nephrectomy or tumor enucleation for the contralateral side, and partial nephrectomy or tumor enucleation for both sides. Two cases of synchronous bilateral renal adenocarcinoma are described. One case was submitted to a left superior partial nephrectomy and enucleation of the tumor in the right kidney. The other patient underwent a left radical nephrectomy and excision of the inferior pole of the right kidney. PMID- 1510492 TI - [Neonatal urinary ascites. Considerations on its diagnosis and treatment]. AB - Seven cases with neonatal urinary ascites are described. In all of the cases the underlying cause was an anatomical or functional obstructive uropathy of the lower urinary tract, the most common pathology being neurogenic bladder secondary to lumbosacral dysphagia. The techniques utilized for patient evaluation (ultrasound, serial micturition cystourethrography and IVP) are described and the findings afforded by each diagnostic technique are presented. The value of serial micturition cystourethrography is underscored. In our view, it is convenient to perform initial diversion by percutaneous nephrostomy, suprapubic punction or placement of a urethral catheter, according to the level of the etiologic process. The definitive surgical approach will depend on the results of subsequent radiologic controls and the existing uropathy. PMID- 1510493 TI - [Piezoelectric extracorporeal lithotripsy in ambulatory care]. AB - The surgical approach for stone disease has completely changed during the last decade. Since 1980, ESWL and Endourology (percutaneous nephrolithotomy, ureteroscopy) have been used worldwide in the treatment of nephrolithiasis and today open surgery is necessary only in less than 5% of the cases. The second generation Wolf Piezolith 2300 is a lithotripter for the painless treatment of the majority of renal and ureteral stones. Treatment of stone patients on an out patient basis in a private clinic commenced in 1988 because of the low complications and side effects related to its use. We report the records of the first 70 patients treated in this way and controlled for at least 3 months after the treatment. PMID- 1510494 TI - [Doppler color echography in varicocele]. AB - The authors report their experience with the color Doppler ultrasound in the diagnosis and follow-up of patients with varicocele. The features and advantages afforded by this technique are described and attention is focussed to the contribution of technological advancement to the urological armamentarium. We report on 18 cases of varicocele, 2 of which were grade I (preclinical), that had been diagnosed by this technique and confirmed at surgery. In this series the scrotal scintiscan proved to be less specific and was falsely negative in one of the two grade I varicoceles. PMID- 1510495 TI - [Bulbocavernosus reflex and somatosensory evoked potential of the pudendal nerve in diabetic impotence]. AB - The present study investigated the sensitivity of the bulvocavernosus reflex (BCR) and the somatosensory evoked potential (SEP) of the pudendal nerve in neurogenic impotence, the study comprised 22 males with diabetes type II. Of these, 11 had neurogenic impotence. The SEP was found to be normal in all cases, whereas BCR changes were observed in 36.4% of the patients who were not impotent and in 63.6% of the impotent males. This difference, however, is not statistically significant. The results show that in diabetic pelvic neuropathy compromise of the vegetative fibers does not necessarily mean injury to the somatic. PMID- 1510496 TI - [Flow studies in patients with sexual erectile dysfunction. Review of the physiology and the adopted method]. AB - Further insight into the physiology of erection acquired in recent years had led to the development of new methods that have enhanced the evaluation of erectile dysfunction. These new methods will permit a more precise diagnosis and, consequently, the management of this condition can be based on scientific and not empirical methods. To date, many questions remain unanswered and many points have not been elucidated. Using a precise methodology will permit us to corroborate or correct what has been done up until now and to develop new methods of investigation. The present study briefly reviews the physiology of erection and describes a method we routinely use. PMID- 1510497 TI - [Giant urethral lithiasis]. AB - Calculi in the male urethra are rare and are generally associated with urethral disorder (diverticuli, stricture, complication posturethroplasty, etc.). Treatment is generally by excision and resolution of the underlying cause. We report a case of urethral calculus, of apparently idiopathic etiology, that had treated by endoscopic ultrasonic disruption. The importance of preoperative etiologic diagnosis is underscored. PMID- 1510498 TI - [Primary carcinoma of the male urethra: review of the literature and presentation of a new case]. AB - A primary carcinoma of the male urethra is described. The etiology, diagnosis, clinical features and treatment of this uncommon tumor are discussed. Because this tumor frequently presents as a benign urethral process, biopsies should be performed in urethral conditions with a torpid clinical course. PMID- 1510499 TI - [Nonpenetrating trauma of the penis. Rupture of corpus cavernosum albuginea]. AB - We report a case of penile trauma that had been treated early by surgery. The value of ultrasound in diagnosing rupture of the corpus cavernosum albuginea is highlighted. The good functional and cosmetic results afforded by early surgical treatment is underscored. PMID- 1510500 TI - [Sexually transmitted recurrent urinary infection of the male]. AB - We describe a case of recurrent urinary tract infection in a male patient that had been repeatedly associated with sporadic sexual intercourse with his partner. The timing of the episodes and the bacteriological findings indicate this to be another uncommon case of urinary tract infection sexually transmitted by the female to the male. PMID- 1510501 TI - [Pulmonary fibrosis secondary to nitrofurantoin]. AB - Herein we report a case of pulmonary fibrosis secondary to chronic administration of nitrofurantoin following radical surgery for a bladder tumor and urinary intestinal diversion. The patient developed pulmonary superinfection and acute respiratory failure. She initially responded to treatment, but relapsed after two weeks. She died from the underlying disease. PMID- 1510502 TI - [Iatrogenic invagination of the ureteral mucosa in renal transplantation]. AB - A case of antegrade invagination of the ureteral mucosa is described. This iatrogenic complication of endourology resulted from percutaneous dilatation with teflon catheters of a stricture in the ureter of a renal graft transplanted 4 years earlier. Definitive correction was by open surgery, which achieved good results. PMID- 1510503 TI - Embolotherapy of priapism. AB - Some cases of idiopathic priapism are due to uncontrolled, penile arterial inflow. These cases can be successfully treated by percutaneous transcatheter embolization of one or both internal pudendal arteries. Autologous clot is ideal for embolization as it permits revascularization and helps avoid impotence. The authors describe a 10-day old case of refractory priapism which was successfully treated angiographically. PMID- 1510504 TI - Heterotopic transplantation: is it a viable alternative? PMID- 1510505 TI - Present role of thoracoscopy in the diagnosis and treatment of diseases of the chest. AB - Since thoracoscopy was originally described in 1910, the application has been limited mainly to the diagnosis and treatment of pleural disease. Recent advancements in endoscopic equipment and refinement of surgical techniques have expanded the application of this procedure. Using video thoracoscopic techniques in 70 patients over the past 9 months, we have been able to perform a variety of procedures previously accomplished by "open" techniques. These procedures include (1) wedge resections of pulmonary nodules in 21 patients, using endoscopic mechanical stapling devices; (2) excision of the pericardium and drainage of the pericardial space in 6 patients; (3) dorsal thoracic sympathectomy in 6 patients; (4) apical blebectomy and pleurodesis in 6 patients; (5) lung biopsies for diagnosis of diffuse lung disease in 5 patients. Additional procedures performed include biopsy of hilar masses (3), biopsy of esophageal mass, excision of a mediastinal cyst, and the drainage of a spinal abscess. The remaining 20 procedures were performed for the diagnosis and treatment of pleural disease. There was no mortality associated with the procedure and morbidity was lessened, compared with standard thoracotomy procedures. The postoperative hospital stay after elective procedures performed in well patients averaged 3 days and was often as short as 1 day. Our experience indicates a markedly expanded role for thoracoscopy in the diagnosis and treatment of thoracic diseases with less postoperative morbidity. PMID- 1510506 TI - Videothoracoscopic wedge excision of the lung. AB - Recent advances in video technology and endoscopic instrumentation have expanded the use of thoracoscopy from diagnosis to treatment of pulmonary parenchymal disease. We recently performed 14 pulmonary wedge excisions using videothoracoscopic techniques in 10 patients (7 women and 3 men). Median age was 60 years (range, 21 to 82 years). Indications were small peripheral solitary pulmonary nodules in 4 patients, diffuse pulmonary infiltrates in 4, and recurrent pneumothoraces in 2. Thoracoscopic wedge excisions were accomplished using double-lumen endotracheal anesthesia and a percutaneous stapling device. Tissue diagnosis was obtained in all patients; 6 had benign disease, 3 had metastatic cancer, and 1 had diffuse bronchoalveolar cell carcinoma. Median operating time was 90 minutes (range, 40 to 140 minutes). There were no operative deaths. The single complication was a prolonged air leak. Median hospitalization was 5 days (range, 3 to 16 days). All patients returned to full activity within 10 days of discharge. Median follow-up was 6 months (range, 5 to 8 months). We conclude that videothoracoscopic wedge excision is a safe and effective procedure for selected small peripheral indeterminate pulmonary nodules, diffuse interstitial lung diseases, and recurrent spontaneous pneumothoraces. Further evaluation and prospective studies are indicated. PMID- 1510507 TI - Thoracoscopic resection of 85 pulmonary lesions. AB - Advances in endoscopic surgical equipment and laser technology have expanded the role of thoracoscopy to include thoracoscopic pulmonary resection. Eighty-five thoracoscopic pulmonary resections were performed on 61 consecutive patients with small lesions (less than 3 cm) in the outer third of the lung. Patients with preoperative histologic evidence of bronchogenic carcinoma were excluded unless there was impairment of cardiopulmonary function, advanced age, or concomitant extrathoracic malignancy. These thoracoscopic pulmonary resections were accomplished with the neodymium:yttrium-aluminum garnet laser (31), endoscopic stapler (29), or both (25). The mean diameter of the lesions was 1.3 cm (range, 0.4 to 2.7 cm). There has been one late death (38th postoperative day) unrelated to the operation. Morbidity consisted of postoperative atelectasis (2), pneumonia (2), bleeding requiring transfusion (1), and bronchopleural fistula of greater than 7 days duration (3). There were no wound problems. The mean period of chest tube drainage was 3.3 +/- 3.0 days. Mean postoperative stay was 5.7 +/- 4.9 days. The pathologic diagnosis was benign disease in 28 patients (interstitial fibrosis/pneumonitis, 15; radiation fibrosis, 1; sclerosing hemangioma, 1; rheumatoid nodules, 1; granuloma, 2; nocardia, 1; infarct, 1; hamartoma, 4; scar, 1; cytomegalovirus pneumonia, 1), metastatic malignancy in 20 patients, and bronchogenic carcinoma in 13 patients. Five patients found at thoracoscopic pulmonary resection to have bronchogenic cancer had adequate pulmonary function and therefore underwent formal segmentectomy (3) or lobectomy (2). Thoracoscopic pulmonary resection was the only operation performed on patients with benign disease, patients with metastatic lesions, and selected patients with limited stage bronchogenic carcinoma at increased risk for thoracotomy.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1510508 TI - One hundred consecutive patients undergoing video-assisted thoracic operations. AB - Video-assisted thoracic surgery is a new modality that allows visualization of and access to the intrathoracic organs without making a thoracotomy incision. One hundred consecutive patients underwent 113 thoracic procedures using this technique. Eight wedge resections for metastatic lesions, 6 pericardial windows, 1 bronchogenic cystectomy, 4 explorations of the aortopulmonary window, 1 decortication, 5 pleural scleroses, 8 bullous ablations, 25 lung biopsies, 19 wedge resections for carcinoma, 9 explorations of the thorax, 3 lobectomies, 1 esophageal cystectomy, 14 wedge resections for benign lesions, 4 pleurectomies, 1 excision of a neurogenic tumor, 3 mediastinal explorations, and 1 imaged axillary dissection were performed. There was no mortality. Ten patients had complications from which they recovered completely. Patients undergoing video-assisted thoracic operations seem to have reduced postoperative pain, shorter hospitalization, and quicker recovery times. Currently, this new modality appears to have beneficial value for patients; however, only further experience will determine its true merits. PMID- 1510509 TI - Composite valve graft replacement of the proximal aorta: comparison of techniques in 348 patients. AB - Composite valve graft replacement of the ascending aorta is being increasingly used, although it is not clear which technique, the Bentall, Cabrol, or button, is the best method for coronary artery ostial reattachment. We retrospectively analyzed our results with respect to these three techniques in 348 consecutive patients operated on between September 17, 1979, and January 29, 1991. Variables included aortic arch replacement in 88 patients (25%), need for deep hypothermia and circulatory arrest in 119 (34%), aortic dissection in 131 (38%), acute dissection in 34 (9.8%), reoperation in 79 (23%), and insertion of St. Jude prostheses in 270 (78%). The 30-day survival rate was 91% (316/348), the in hospital survival rate was 90% (312/348), and the 30-day incidence of postoperative new transient (n = 6) and permanent (n = 6) stroke was 3% (12/348). The 30-day survival rates for each method were as follows: Cabrol, 92% (144/157); button, 91% (39/43); and Bentall, 91% (125/137). On stepwise multivariate logistic regression analysis with control for operative date and independent prognostic factors, operative technique was not an independent determinant of early mortality or stroke. On late follow-up, the Kaplan-Meier 5-year survival rate was 71% with no significant difference between the groups (3-year survival: Cabrol, 76%; Bentall, 79%; and button, 81%; p = 0.28). The 3-year freedom from reoperation was 95% (Cabrol, 97%; Bentall, 91%; and button, 100%; p = 0.17). We conclude that for patients undergoing reoperation or complicated repairs or when tension on the ostial anastomoses may occur, the Cabrol technique is preferable. If feasible, however, the button technique has better long-term results for both survival and rate of reoperation. An alternative technique is to use an interposition graft to reattach the left coronary artery and excise an aortic button for the right coronary artery reattachment. This has the advantages of technical ease in reattaching the left coronary artery, good results for reattachment of the right coronary artery, minimal tension on the anastomoses, and visualization of all anastomoses. PMID- 1510510 TI - Factors affecting mitral valve reoperation in 317 survivors after mitral valve reconstruction. AB - From a very heterogeneous group of 340 patients undergoing mitral valve reconstruction from 1969 through 1988, 313 hospital survivors were analyzed for factors affecting the occurrence of reoperative mitral valve procedures related to native mitral valve dysfunction. Follow-up was 100% and extended from 1 year to 20 years (mean follow-up, 7.2 years). Sixty-three patients (18.5% of the 340) required mitral valve reoperation at a mean postoperative interval of 6 years (range, 1 to 15 years). Incremental risk factors analyzed for the event late mitral valve failure included age, sex, preoperative New York Heart Association class, cause of valvular disease, pathophysiology of the mitral valve, previous mitral valve operation, mitral valve pathology, and estimation of mitral valve function at operation after repair. Mitral valve pathophysiology affected the actuarial freedom from mitral valve replacement (p = 0.023 [log-rank]). Actuarial freedom from mitral valve reoperation was 90% at 5 years and 80% at 8 years in patients who had either pure mitral regurgitation or isolated mitral stenosis compared with 80% and 72% at 5 and 10 years, respectively, in patients who had mixed mitral stenosis and regurgitation (p = 0.023). Patients undergoing late reoperation were younger (51.7 +/- 1.56 years [+/- the standard error of the mean]) than those not having reoperation (p less than 0.0003). Durability of the repair was less in patients with rheumatic heart disease (p less than 0.025) and greater in patients with ischemic heart disease (p less than 0.004). Seventy three percent of patients undergoing reoperation had concomitant operations compared with 68% of those not having reoperation (p less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1510511 TI - A randomized study of the systemic effects of warm heart surgery. AB - The technique of warm heart surgery is defined as continuous warm blood cardioplegia and normothermic cardiopulmonary bypass. Although the systemic effects of traditional myocardial protection are well known, the effects of warm heart surgery are not. In a prospective trial, 204 patients undergoing coronary artery bypass grafting were randomized to the warm heart surgery technique (normothermic group) or traditional intermittent cold blood cardioplegia and cardiopulmonary bypass (hypothermic group). The groups had similar heparin sodium requirement, activated clotting times, urine output, hematocrit, and blood product utilization. There were no differences in hemodynamics immediately after cardiopulmonary bypass. The normothermic patients had a higher incidence of spontaneous defibrillation at cross-clamp removal (84%) than the hypothermic patients (33%) (p less than 0.01). An increase in the flow rate of low K+ cardioplegia was necessary to eradicate electrical activity during aortic occlusion more often in the normothermic patients (20%) than in the hypothermic patients (3%) (p less than 0.01). When low K+ cardioplegia was ineffective, high K+ cardioplegia was necessary to eradicate electrical activity in 31% of the normothermic patients compared with 10% of the hypothermic patients (p less than 0.05). The total cardioplegia volume delivered to the normothermic group (4.7 +/- 1.9 L) was higher than that delivered to the hypothermic group (2.6 +/- 0.8 L) (p less than 0.01). Although urine output was similar in both groups, the serum K+ levels were higher in the normothermic group (5.7 +/- 0.8 mmol/L) than in the hypothermic group (5.3 +/- 0.8 mmol/L) (p less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1510512 TI - Optimum treatment of discrete subaortic stenosis. AB - Discrete subaortic stenosis typically appears as a well-defined membrane beneath the aortic valve. To assess the merits of alternative approaches to this problem, we have reviewed the results of operations for discrete subaortic stenosis from 1978 through 1990. Excision of the subaortic membrane alone was performed in 16 patients (group I). Excision of the membrane with resection of septal muscle was performed in 24 patients (group II). The groups were similar in age at operation, duration of follow-up, and preoperative and postoperative transvalvar gradients. There were no operative or late deaths. Reoperations for recurrent subaortic stenosis were performed in 4 group I patients (25%; 70% confidence limits, 16% to 38%) and 1 group II patient (4%; 70% confidence limits, 2% to 11%). Pacemakers were inserted for postoperative complete heart block in 1 group I patient (6%; 70% confidence limits, 2% to 16%) and 2 group II patients (8%; 70% confidence limits, 4% to 16%). We conclude that muscle resection combined with membrane excision in patients with discrete subaortic stenosis does not increase the risk of death or heart block, and does lower the risk of reoperation for recurrent subaortic stenosis. PMID- 1510513 TI - Normothermic cardioplegia: is aortic cross-clamping still synonymous with myocardial ischemia? AB - The enthusiastic clinical reports on normothermic blood cardioplegia contrast with the paucity of data on the myocardial metabolic effects of this technique. The present study was therefore designed to assess whether normothermic blood cardioplegia really provides an aerobic environment during aortic cross-clamping. Thirty-one patients undergoing coronary (16 patients), valve (13 patients), and transplantation (2 patients) procedures were given continuous normothermic blood cardioplegia through the coronary sinus. Myocardial metabolism was assessed either immediately before aortic unclamping (16 patients) by collecting blood simultaneously from the cardioplegia infusion line and the aortic effluent or during reperfusion (15 patients) by collecting blood simultaneously from the radial artery and the coronary sinus. All samples were assayed for markers of anaerobiosis (blood gases, lactates), leukocyte activation (elastase), and lipid peroxidation (malondialdehyde, vitamin E). At the end of arrest, oxygen extraction was low, whereas the production of lactates was small, thereby suggesting the efficacy of normothermic blood cardioplegia in maintaining a predominantly aerobic metabolism. This was confirmed by postarrest data, as oxygen extraction measured immediately after cross-clamp removal was unchanged from prearrest values, whereas lactate metabolism yielded transient and limited production followed by prompt recovery of normal extraction patterns. There was no release of elastase from the myocardium, which suggests adequate protection of the coronary endothelium from ischemic injury and the related increase in leukocyte activation. Likewise, postarrest coronary sinus concentrations of malondialdehyde and vitamin E were identical to the respective arterial concentrations, thereby ruling out the occurrence of intramyocardial lipid peroxidation at the time of reperfusion.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1510514 TI - Subcutaneous use of erythropoietin in heart surgery. AB - The effect of subcutaneous administration of recombinant human erythropoietin (rHuEPO) in ameliorating anemia resulting from autologous blood donation was compared with intravenous administration of rHuEPO. Forty patients undergoing coronary artery bypass procedures were divided into three groups. Group I (12 patients) received intravenous administration of rHuEPO (100 U.kg-1.day-1) and intravenous iron preparations for 14 days before operation; group II (14 patients) had subcutaneous administration of rHuEPO (600 U/kg) on preoperative days 14 and 7 and oral iron preparations for 14 days; and group III (14 patients) received oral iron preparations alone and served as the controls. Each patient predonated 800 mL of blood in the 2 weeks before operation. The reticulocyte count increased significantly in groups I and II (p less than 0.01), but little in group III. The hemoglobin level just before operation was higher in groups I (p less than 0.01) and II (p less than 0.05) compared with group III. Four patients (29%) in group III required homologous blood transfusion versus none in groups I and II (p less than 0.05). Subcutaneous administration of rHuEPO once a week was as effective as daily intravenous administration. Preoperative autologous blood donation can be performed over a short period on an outpatient basis with subcutaneous administration of rHuEPO. PMID- 1510515 TI - Atrioventricular pacing in congenital heart disease. AB - We have attempted to optimize cardiac performance in patients with congenital heart disease requiring artificial pacing by using pacemakers capable of both sensing and pacing both the atrium and the ventricle (DDD). We reviewed our results with 88 patients receiving DDD devices to determine the safety and dependability of these devices in children. Age ranged from 1 hour to 25 years. Endocardial leads were used in 68 patients, whereas epicardial leads were used in 20 patients. Previous cardiac procedures had been done in 30 patients. There were nine deaths but none due to pacemaker malfunction. Endocardial leads functioned better than epicardial leads. Ninety-eight percent of patients with endocardial leads and 62% of patients with epicardial leads were maintained in the DDD mode. Complications were infrequent and all were corrected without long-term sequelae. The DDD mode may offer considerable benefits to children who require artificial pacing. Our data allow us to conclude that most children can be paced safely and dependably in the DDD mode. PMID- 1510516 TI - Thoracoscopic lung biopsy. AB - Progress in instrumentation and techniques developed for laparoscopic surgery have paved the way for a resurgent interest in thoracoscopic procedures. Traditional thoracoscopy was limited by access, restricted visualization, and surgical devices. Recent cases provided an opportunity to successfully perform thoracoscopic pulmonary wedge excisions using state-of-the-art technology and instruments adapted from laparoscopy. These preliminary cases provided an opportunity to modify and adapt these techniques to thoracic procedures. Video thoracoscopy is rapidly evolving in both methods and instrumentation. PMID- 1510517 TI - Human cardiac nerve stimulation. AB - Cardiovascular responses were elicited in 12 patients undergoing cardiac operations when cardiopulmonary neural elements between the aortic root and pulmonary artery or in the right atrial ganglionated plexus were stimulated. Heart rate and left ventricular intramyocardial systolic pressure were augmented when cardiopulmonary nerves between the aorta and pulmonary artery were stimulated in 11 of the 12 patients. Right ventricular intramyocardial systolic pressure was augmented in 7 of these 11 patients. Cardiodepressor responses were elicited when the right atrial ganglionated plexus (9 patients) or a cardiopulmonary nerve (2 patients) was stimulated. These results demonstrate that electrical stimulation of the human extrinsic and intrinsic cardiac nervous systems can alter cardiodynamics, different responses being elicited when different neural structures are stimulated. These data are in accord with those obtained from canine experiments and suggest that the human extrinsic and intrinsic cardiac nervous system contains functionally similar neural elements to those found in other mammals. PMID- 1510518 TI - Is use of the intraaortic balloon pump in octogenarians justified? AB - Increasing numbers of octogenarians are seen in the operating room or critical care unit with circumstances for which intraaortic balloon pump (IABP) assistance is appropriate, but it has been suggested that the complication rate for IABP use in octogenarians is excessive. From 1980 to 1990, 25 octogenarians needed an IABP in our institution, as an adjunct to operation in 20 patients (1 had repair of a ventricular rupture and 19 underwent coronary grafting); 5 patients did not have operation. The indications for IABP use were unstable angina, 12 (48%); cardiogenic shock, 10 (40%); and difficulty weaning off cardiopulmonary bypass, 3 (12%)--these 3 were the only ones who had insertion through a femoral cut-down. No serious insertion difficulties were noticed with the percutaneous route in the other 22 patients. Without operation, 4 of 5 patients died in the hospital (80%), and the 5th died 2 years 8 months after discharge. After operation, there were two hospital deaths (10%) and two late deaths, neither from cardiac causes. A fatal outcome occurred in 6 of 9 patients with cardiogenic shock. Intraaortic balloon pump-related complications were rare, minor, and unrelated to IABP assistance duration, which ranged from 24 to 146 hours (mean, 49.9 hours). No long-term vascular complications resulted. Hospital stay averaged 22.2 days. At follow-up from 9 to 81 months (mean, 51.8 months), of the 16 survivors, 12 (75%) were in New York Heart Association class I/II and 2 each were in classes III and IV.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1510519 TI - Multicenter trial of automated nitroprusside infusion for postoperative hypertension. Titrator Multicenter Study Group. AB - Hypertension is common after a cardiac operation and may result in postoperative hemorrhagic and other complications. Most often this problem has been treated using manually controlled doses of intravenous sodium nitroprusside. To evaluate the clinical impact of an automated closed-loop administration system on patients after cardiotomy, a prospective trial was conducted at nine clinical centers. Patients with hypertension were managed by either manual nitroprusside titration (n = 532) or a closed-loop automated titration system (n = 557). Patient groups were not significantly different in age, weight, or height. Moreover, the types of surgical procedures were comparable: primary coronary artery bypass grafting, 59.2% and 58.9%, manual group versus automated group; repeat coronary artery bypass grafting, 10.5% and 8.6%, respectively; valve procedures, 11.3% and 15.1%, respectively; and other cardiac procedures, 19.0% and 17.4%, respectively (all p = not significant). The automated group showed a significant reduction in the number of hypertensive episodes per patient (1.8 +/- 0.2 versus 0.6 +/- 0.07; p = 0.0001. At the same time, the number of hypotensive episodes per patient was reduced with automated closed-loop titration (0.40 +/- 0.05 versus 0.30 +/- 0.03; p = 0.02). Chest tube drainage (866 +/- 37 mL versus 693 +/- 23 mL [mean +/- standard error of the mean]; p = 0.0001), percentage of patients receiving transfusion (40.0% versus 33.0%; p = 0.02), and total amount transfused (2.4 +/- 0.12 units versus 2.0 +/- 0.10 units; p = 0.0003) were all reduced significantly by the use of an automated titration system.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1510520 TI - Modified Fontan procedure for severe Ebstein's malformation with predominant tricuspid stenosis. AB - Two children, aged 7 and 6 years, had severe Ebstein's malformation of the tricuspid valve and underwent operation because of progressive cyanosis (saturation, 70%). Preoperative angiography demonstrated linear attachment of the distal edges of the displaced anterosuperior and mural leaflets, leaving only a "keyhole" communication between the atrialized and functional portions of the right ventricle. Operation was directed toward completely excising these dysplastic leaflets, which were obstructing the flow of blood. The continuity between the functional right ventricle and pulmonary trunk was left intact. In addition, an atriopulmonary truncal connection was established. Postoperatively, both children were in functional class I with arterial saturation of 95%. Angiography and Doppler echocardiography demonstrated that there was a dominant phase of systolic flow of blood up the pulmonary trunk from the right ventricle, and also diastolic filling of the pulmonary arteries through the atriopulmonary truncal connection. The filling patterns did not change over time for the follow up period of 4 and 1.5 years, respectively. This modified Fontan procedure appears to be an effective surgical alternative for some patients with severe Ebstein's malformation and predominant tricuspid stenosis. PMID- 1510521 TI - Experience in 100 transthoracic balloon pumps. AB - We retrospectively reviewed our last 100 consecutive patients who had an intraaortic balloon pump (IABP) placed through the ascending aorta for postoperative cardiogenic shock. Eighty-one patients survived to have their IABP removed and were evaluated for complications. Complications that may have been related to the transthoracic route of IABP introduction included balloon rupture in 6.2% (5/81), cerebral vascular accident in 2.5% (2/81), transient ischemic attack in 1.2% (1/81), bleeding at the IABP arteriotomy site in 3.7% (3/81), and mediastinitis in 3.7% (3/81). Compared with expected rates of development of complications in this high-risk group of patients, it appeared that balloon rupture and mediastinal bleeding were increased because of the transthoracic placement of the IABP. The rates of neurologic events and mediastinal infection do not appear to be increased. Transthoracic IABP placement avoids ischemic problems in the lower extremities and has proved a useful route for IABP introduction. PMID- 1510522 TI - Long-term results of St. Jude Medical valve in the tricuspid position. AB - Little is known of the St. Jude Medical heart valve's long-term clinical performance in the tricuspid position. Fourteen patients underwent tricuspid valve replacement between 1981 and 1984. Ages of the patients ranged from 32 to 81 years. Eight patients (68%) were in New York Heart Association class IV preoperatively. Twelve patients had other concomitant cardiac operations. One patient (8%) died within 30 days after operation, due to cerebrovascular accident. Postoperatively, all patients were anticoagulated with warfarin sodium and showed improvement in functional class. There were no mechanical valve failures or thromboses in patients on the anticoagulation regimen. Follow-up in all patients extended over 7 to 10 years with a mean of 8 years. There were six late deaths unrelated to valve function. The actuarial survival curve with these patients is 50% over 10 years. In conclusion, the St. Jude Medical valve is a good mechanical substitute in the tricuspid position, and we recommend its use when reconstruction is not possible and there is no contraindication for anticoagulation. PMID- 1510524 TI - Attenuation of waiting time mortality with heterotopic heart transplantation. AB - As the number of heart transplants and the number of transplant programs has increased, so has the waiting time for a suitable organ. To more accurately assess the magnitude of this increase and the influence of recipient size, we reviewed waiting times for large (body surface area greater than or equal to 1.95 m2) and small (body surface area less than 1.95 m2) patients with respect to era of transplantation. Patients who underwent transplantation early (1984 to December 31, 1986) waited 35 +/- 47 days (mean +/- standard deviation), whereas patients who underwent transplantation in the late era (1987 to September 30, 1989) waited 83 +/- 102 days (p = 0.001). Large patients waited longer (130 +/- 142 days) in the late era than did small patients (60 +/- 67 days; p = 0.008). During the heterotopic era (October 1, 1989 to June 30, 1990), waiting times for large patients who received a heterotopic transplant (67 +/- 46 days) were significantly shorter than those for patients who received an orthotopic transplant (166 +/- 157 days; p = 0.05). Waiting times for small patients remained unchanged. In addition, waiting time mortality decreased from 24% to 9% (p less than 0.05). Comparison of orthotopic and heterotopic procedures performed during the same era revealed no significant differences in recipient age, preoperative status, graft ischemic time, donor age, early and midterm survival, or early postoperative functional status. Heterotopic heart transplantation may effectively increase the size of the donor pool, decrease the waiting time, and decrease waiting time mortality without increasing the morbidity of the procedure. PMID- 1510525 TI - Cardiac valve replacement in patients infected with the human immunodeficiency virus. AB - Major surgical procedures, especially when performed under general anesthesia, can depress immunological parameters measured in vitro. Therefore concern has been expressed that operation might have an adverse effect on the immune status of individuals infected with the human immunodeficiency virus (HIV). Four HIV positive patients without symptoms of HIV disease underwent cardiac valve replacement in consequence of infective endocarditis. After up to 15 months postoperatively, 3 patients are alive and well without signs of progressive immunodeficiency or recurrent endocarditis. One patient died of recurrent endocarditis without evidence of HIV-related disease on autopsy. Cardiac operation does not seem to accelerate HIV-related immunodeficiency. PMID- 1510523 TI - Coagulation defects in neonates during cardiopulmonary bypass. AB - We examined components of the coagulation system in 30 neonates (age, 1 to 30 days) undergoing deep hypothermic cardiopulmonary bypass (CPB). A coagulation profile consisting of activated clotting time; prothrombin time; partial thromboplastin time; factors II, V, VII, VIII, IX, X, and I (fibrinogen); antithrombin III; platelet count; and heparin levels was evaluated before bypass, at three intervals during bypass (1 minute after initiation of bypass, stable hypothermic CPB, warm CPB), after weaning from CPB and administration of protamine, and 2 to 3 hours after skin closure. The initiation of CPB resulted in a 50% decrease in circulating coagulation factors and antithrombin III levels. Platelet counts were reduced by 70% with CPB initiation. Neither deep hypothermic temperatures nor prolonged exposure to extracorporeal surfaces had any additional effect on the coagulation profiles. This suggests that the coagulation system of a neonate undergoing CPB is profoundly and globally effected by hemodilution. We believe that treatment of post-CPB coagulopathy in neonates must address these global deficits. PMID- 1510526 TI - Repair of aortico-left ventricular tunnel associated with subpulmonary obstruction. AB - Aortico-left ventricular tunnel is a rare congenital cardiac defect. Because the tunnel traverses the upper portion of the interventricular septum, the potential exists for an aneurysmal tunnel to obstruct the outflow of the right ventricle. We report our clinical experience with such a patient, and emphasize the importance of a two-patch technique to avoid its occurrence. PMID- 1510527 TI - Mediastinal window: a cause of simultaneous bilateral spontaneous pneumothorax. AB - A case of bilateral spontaneous pneumothorax with critical collapse of both lungs in a previously healthy 19-year-old woman is described. A congenital defect of mediastinal septum was suspected on the basis of roentgenographic findings and confirmed by right-sided thoracotomy. This mediastinal window between the pleural spaces allowed air leaking from a ruptured right lung apical bulla to collapse not only the right lung but also the left. Apical TA stapler resection and right sided parietal pleurectomy was performed to prevent recurrence. PMID- 1510528 TI - Intraoperative echocardiographic diagnosis of previously unrecognized cor triatriatum. AB - Cor triatriatum is a congenital heart defect resulting in abnormal septation of the left atrium by a fibromuscular membrane. Echocardiography has improved the preoperative diagnosis of this rare congenital heart defect. We report a case where transesophageal echocardiography proved useful in the intraoperative diagnosis of a previously undetected cor triatriatum. PMID- 1510529 TI - Anastomotic ulcer-induced aortoenteric fistula after esophagogastroplasty. AB - A 67-year-old woman underwent an esophagogastrectomy and esophagogastrostomy for carcinoma of the distal esophagus. She died of massive hematemesis and exsanguination on the 14th postoperative day. An acute peptic ulcer-induced aortoenteric fistula was present at the anastomotic line. The literature on peptic ulcer-induced aortoenteric fistulas after esophagogastroplasty is reviewed. PMID- 1510530 TI - Retrograde cerebral perfusion with circulatory arrest in aortic arch aneurysms. AB - Two surgical cases of aortic arch aneurysms are presented. Retrograde (venoarterial) cerebral perfusion during circulatory arrest under deep hypothermia was performed to evacuate air and debris in cerebral vessels and preserve cerebral tissue. On postoperative day 1, the patients were conscious and alert with no neurological deficit. This technique is simple and can be applied during standard cardiopulmonary bypass. The technique is useful to avoid cerebral air and thromboembolisms. PMID- 1510531 TI - Pericardioperitoneal shunt for persistent pericardial effusions: a new drainage procedure. AB - We report a pericardioperitoneal shunt procedure in 2 patients with persistent pericardial effusions in which the classic surgical methods of shunting were inappropriate. PMID- 1510532 TI - Coronary artery bypass grafting nine years after cardiac transplantation. AB - Angina and increasing exertional dyspnea developed in a 53-year-old man 9 years after cardiac transplantation. Left heart catheterization revealed severe proximal triple coronary artery disease, and he underwent surgical revascularization. Now 18 months after the operation he continues to be free of symptoms. PMID- 1510533 TI - Systemic atrioventricular valve replacement in an infant with corrected transposition of the great arteries. AB - A 3-month-old infant with corrected transposition of the great arteries and severe systemic atrioventricular valve regurgitation due to "Ebstein-like anomaly" is reported. Through a right thoracotomy and longitudinal left atrial incision, a 19-mm St. Jude Medical valve was implanted into the annulus without removing the native valve. He is doing well 7 months after operation. PMID- 1510534 TI - Videothoracoscopic enucleation of esophageal leiomyoma. AB - A new thoracoscopic technique to enucleate esophageal leiomyomas is described. The procedure has been successfully performed in 3 patients. All patients benefited by this new surgical approach due to the decreased operative trauma, reduced postoperative pain, quick recovery, and minute skin scars. Although further clinical experience and longer periods of follow-up are needed to evaluate the full benefits and limits of this new access, the early results of the thoracoscopic approach are promising. PMID- 1510535 TI - Placement of an endotracheal tube in the short tracheal stump. AB - Placement of an endotracheal tube in the short tracheal stump, such as after a mediastinal tracheostomy, can be a difficult task. The tube may easily slide into the right main bronchus or slip out of the trachea completely. We have described a method for securing such an airway for ventilation during general anesthesia. PMID- 1510536 TI - Simple method to monitor pulmonary artery pressure in infants after cardiac operations. AB - Intraoperative placement of catheters to monitor pulmonary artery pressure and cardiac output by oximetry can easily be accomplished under direct vision. The insertion through a saphenous vein cutdown assures a much safer removal, eliminating the risk of bleeding, tamponade, and catheter entrapment. PMID- 1510537 TI - Management of aortic cannulation site blowouts. AB - An alternative technique of handling the aortic cannulation site blowout is described. The cannulation site is excluded with a side-biting clamp. The area is excised. Pericardial patch is sewn in to cover the defect. PMID- 1510538 TI - Pericardioplasty. AB - When so desired, a simple technique can be performed to close the pericardium after a cardiac operation. The only requirement is to think about it during the opening of the pericardium and make the appropriate cuts. PMID- 1510539 TI - Current concepts concerning the nature and treatment of Barrett's esophagus and its complications. AB - Current concepts regarding the nature and the treatment of Barrett's esophagus and its complications are reviewed. The columnar-lined lower esophagus is being increasingly recognized as an acquired condition caused by gastroesophageal reflux. Many patients are asymptomatic. Barrett's esophagus occurs in about 10% to 15% of patients with reflux esophagitis. The diagnosis depends on endoscopy and biopsy. Complications are common and include ulceration, stricture, dysplasia, and adenocarcinoma. Esophagitis, ulceration, and stricture can usually be treated medically. Surgical approaches are discussed for patients whose condition is refractory to medical therapy. The premalignant nature of Barrett's epithelium is well recognized, and strategies for surveillance and resection are discussed. Survival after resection of adenocarcinoma in Barrett's esophagus is not appreciably different from that of other carcinomas. Surveillance with endoscopy offers the best chance for early detection and cure. PMID- 1510540 TI - Dynamic cardiomyoplasty. PMID- 1510541 TI - Combined superior and right lateral left atriotomy with division of the superior vena cava for exposure of the mitral valve. PMID- 1510542 TI - Profound hypothermia and circulatory arrest. PMID- 1510543 TI - Extended approach to the mitral valve. PMID- 1510544 TI - Visualization of coronary artery anastomoses by gas jet. PMID- 1510545 TI - Homograft root replacement for juvenile rheumatoid aortic valve incompetence. PMID- 1510546 TI - Internal mammary artery to lung parenchyma fistula. PMID- 1510547 TI - Projections from cortical visual areas of the superior temporal sulcus to the superior colliculus, in macaque monkeys. AB - 1. The distribution of tectal projections of two visual areas of the superior temporal sulcus (MT and MST areas) has been studied, in five Macaca fascicularis, by means of the autoradiographic method tracing the anterograde transport of tritiated aminoacids intracortically injected. 2. In all cases the ipsilateral superior colliculi (SC) were found labelled, whereas the contralateral ones were devoid of label. 3. The three brains injected in the MT area resulted in SC labels that involved the superficial gray layer (SGS), the stratum opticum (SO) and the intermediate gray layer (SGI), sparing the layers below SGI. 4. The collicular labels found after injections within the MST area exhibited their distribution over the deep SC subdivision, whereas they spared all the superficial layers but the deep part of the SO. 5. In two animals with large uptake zones, one in MT and the other in MST, the labelling within the SGI showed a cluster-like pattern. 6. The distinct found bulk of projections of MT and MST respectively to the superficial and deep subdivisions of the SC, along with a number of peculiar connections of the MST area as mentioned in the text, contribute to depict an overall neural network in which MST appears to be more strongly involved than MT in linking sensory visual with oculomotor attentive functions. PMID- 1510548 TI - Activity of cat cerebellar neurons in penicillin epilepsy and amphetamine treatment. AB - The discharge pattern of cerebellar Purkinje cells and fastigial neurons was studied after acute amphetamine treatment in immobilized cats, as well as during generalized penicillin-induced epilepsy. There was a marked reversible decrease in spontaneous firing rate of Purkinje cells and an increase in spontaneous firing rate of fastigial neurons after acute d-1 amphetamine administration (5 mg/kg, s.c.). The discharge pattern of Purkinje cells showed tendency towards inhibition, while the fastigial neurons showed less clear tendency towards disinhibition in the course of epilepsy induced by parenteral administration of penicillin (400.000-500.000 I.U./kg, i.m.). Moreover, acute amphetamine treatment (5 mg/kg, s.c.) performed after the development of penicillin-induced epileptic episodes elicited a prominent suppression of Purkinje cell discharges associated with a parallel increase in discharges of fastigial neurons. These results suggest that the changes in discharge rate of cerebellar corticonuclear neurons induced by amphetamine contribute to suppression of seizural activity in the feline model of generalized epilepsy. PMID- 1510549 TI - Single unit activity in the guinea-pig cochlear nucleus during sleep and wakefulness. AB - The effects of waking and sleep on the response properties of auditory units in the ventral cochlear nucleus (CN) were explored by using extracellular recordings in chronic guinea-pigs. Significant increases and decreases in firing rate were detected in two neuronal groups, a) the "sound-responding" and b) the "spontaneous" (units that do not show responses to any acoustic stimuli controlled by the experimenter). The "spontaneous" may be considered as belonging to the auditory system because the corresponding units showed a suppression of their discharge when the receptor was destroyed. The auditory CN units were characterized by their PSTH in response to tones at their characteristic frequency and also by the changes in firing rate and probability of discharge evaluated during periods of waking, slow wave and paradoxical sleep. The CNS performs functions dependent on sensory inputs during wakefulness and sleep phases. By studying the auditory input at the level of the ventral CN with constant sound stimuli, it was shown that, in addition to the firing rate shifts, some units presented changes in the temporal probability of discharge, implying central actions on the corresponding neurons. The mean latency of the responses, however, did not show significant changes throughout the sleep-waking cycle. The auditory efferent pathways are postulated to modulate the auditory input at CN level during different animal states. The probability of firing and the changes in the temporal pattern, as shown by the PSTH, are thus dependent on both the auditory input and the functional brain state related to the sleep-waking cycle. PMID- 1510550 TI - Electrophysiological relations between the superior colliculus and the red nucleus in the cat. AB - The electrical activity of single units located in the parvicellular part of the red nucleus (pRP) was recorded extracellularly in nitrous oxide anesthetized and C1-transected adult cats. In this area, neurons were found to respond to electrical stimulation applied to intermediate and deep layers of the right superior colliculus (SC). Forty neurons located in the pRN of both sides were studied. Three neurons out of 18 (16.6%) located in the contralateral pRN and six neurons out of 22 (27.3%) located in the ipsilateral pRN were driven by the right SC stimulation. The pRN neurons were separated into four groups according to the latency response to the SC stimulation: 1) 0.6-1.9 ms, 2) 2-4 ms, 3) 4-6 ms, 4) variable latency responses. Each of these four groups of neurons showed a particular pattern of discharge, even though their discharge frequency showed a strong consistency. Four pRN neurons, which responded to SC stimulation, showed a significant correlation with spontaneous horizontal eye movements of saccadic type. It is known that the SC represents one of the main outputs of the striato nigral motor system. The relation between the SC and the pRN described in the present study suggest that connections exist between the cortico-rubral and the striato-nigral systems, since both have the SC as a common output structure. It is likely, therefore, that the cortico-rubral-SC system is involved in the control of oculomotor functions, and that the SC may serve to establish interactions between systems concerned with eye movements. PMID- 1510551 TI - Utilization of methoxylated benzoates and formation of intermediates by Desulfotomaculum thermobenzoicum in the presence or absence of sulfate. AB - Desulfotomaculum thermobenzoicum strain TSB (DSM 6193) was found to utilize some methoxylated benzoates as carbon and energy source with or without sulfate. 3- or 4-Methoxybenzoate, vanillate (4-hydroxy-3-methoxybenzoate), syringate (3,5 dimethoxy-4-hydroxybenzoate) and 3,4,5-trimethoxybenzoate were converted to corresponding hydroxybenzoates. However, neither 2-methoxybenzoate nor 2,6 dimethoxybenzoate was utilized. The organism grew acetogenically on each of the methoxylated benzoates in the absence of sulfate. 3,4-Dihydroxy-5-methoxybenzoate was detected during conversion of syringate, and syringate and 3,4-dihydroxy-5 methoxybenzoate were detected during conversion of 3,4,5-trimethoxybenzoate as intermediates. These findings indicate that 4-methoxyl-group is most readily cleaved, whereas 2-methoxyl-group is not utilized by the organism. PMID- 1510552 TI - Thiobacillus plumbophilus spec. nov., a novel galena and hydrogen oxidizer. AB - From an uranium mine three strains of rod-shaped, mesophilic, chemolithouautotrophic bacteria were isolated. They grow by oxidation of H2S, galena (PbS) and H2. Angelsite (PbSO4) is formed from galena. No ferrous iron is oxidized by the isolates. They grow between pH 4 and 6.5 at temperatures of about 9 to 41 degrees C (optimum around 27 degrees C). The G + C content of the DNA is around 66 mol %. Based on their ability to oxidize sulfur compounds, the new organisms belong to the genus Thiobacillus. No significant homology with Thiobacillus ferrooxidans and Thiobacillus cuprinus was detected by DNA-DNA hybridization. Therefore the new isolates represent a new species within the genus Thiobacillus. Based on the unusual growth on galena, we name the new species Thiobacillus plumbophilus (type strain Gro7; DSM 6690). PMID- 1510553 TI - Periplasmic location of nitrous oxide reductase and its apoform in denitrifying Pseudomonas stutzeri. AB - Immunogold labelling techniques on ultrathin sections of low temperature embedded cells yielded evidence for the periplasmic location of the respiratory enzymes N2O reductase and nitrite reductase (cytochrome cd1) in Pseudomonas stutzeri strain ZoBell. Cell fractionation by spheroplast preparation and two-dimensional electrophoresis showed the absence of a membrane association of these enzymes. Immunocytochemical localization of N2O reductase in a mutant strain deficient in the chromophore of N2O reductase showed the gold label at the cell periphery, indicating that the copper chromophore processing takes place after export of this protein's apoform. PMID- 1510554 TI - Synthesis in vitro of very long chain fatty acids in Vibrio sp. strain ABE-1. AB - The activity of fatty acid synthetase (FAS) from Vibrio sp. strain ABE-1 required the presence of acyl carrier protein and was completely inhibited by thiolactomycin, an inhibitor specific for a type II FAS. These observations indicate that this enzyme is a type II FAS. Analysis by gas-liquid chromatography of the reaction products synthesized in vitro from [2-14C]malonyl-CoA by the partially purified FAS revealed, in addition to 16- and 18-carbon fatty acids which are normal constituents of this bacterium, the presence of fatty acids with very long chains. These fatty acids were identified as saturated and mono unsaturated fatty acids with 20 up to as many as 30 carbon atoms. The longest fatty acids normally found in this bacterium contain 18-carbon atoms. These results suggest that the FAS from Vibrio sp. strain ABE-1 has potentially the ability to synthesize fatty acids with very long chains. PMID- 1510555 TI - Gas vesicles are strengthened by the outer-surface protein, GvpC. AB - The critical collapse pressure of gas vesicles isolated from Anabaena flos-aquae decreased from 0.557 to 0.190 MPa when GvpC, the hydrophilic 22 kDa protein present on the outer surface of the gas vesicle, was removed by rising in 6 M urea. Recombinant GvpC was purified from inclusion bodies, produced in an E. coli strain containing an expression vector bearing the gene encoding GvpC from A. flos-aquae, and then solubilised in 6 M urea. This recombinant GvpC became bound to gas vesicles that had been stripped of their native protein, when the urea was removed by dialysis; the amount which bound increased with the concentration of GvpC present. The critical pressure of these reconstituted gas vesicles increased to 0.533 MPa, 96% of the original value. These results indicate that the function of GvpC is to increase the strength of the structure. PMID- 1510556 TI - Iron control of the Vibrio fischeri luminescence system in Escherichia coli. AB - Iron influences luminescence in Vibrio fischeri; cultures iron-restricted for growth rate induce luminescence at a lower optical density (OD) than faster growing, iron-replete cultures. An iron restriction effect analogous to that in V. fischeri (slower growth, induction of luminescence at a lower OD) was established using Escherichia coli tonB and tonB+ strains transformed with recombinant plasmids containing the V. fischeri lux genes (luxR luxICDABEG) and grown in the presence and absence of the iron chelator ethylenediamine-di(o hydroxylphenyl acetic acid) (EDDHA). This permitted the mechanism of iron control of luminescence to be examined. A fur mutant and its parent strain containing the intact lux genes exhibited no difference in the OD at induction of luminescence. Therefore, an iron-binding repressor protein apparently is not involved in iron control of luminescence. Furthermore, in the tonB and in tonB+ strains containing lux plasmids with Mu dI(lacZ) fusions in luxR, levels of beta-galactosidase activity (expression from the luxR promoter) and luciferase activity (expression from the luxICDABEG promoter) both increased by a similar amount (8-9 fold each for tonB, 2-3 fold each for tonB+) in the presence of EDDHA. Similar results were obtained with the luxR gene present on a complementing plasmid. The previously identified regulatory factors that control the lux system (autoinducer-LuxR protein, cyclic AMP-cAMP receptor protein) differentially control expression from the luxR and luxICDABEG promoters, increasing expression from one while decreasing expression from the other. Consequently, these results suggest that the effect of iron on the V. fischeri luminescence system is indirect. PMID- 1510557 TI - Lethal and mutational effects of solar and UV radiation on Staphylococcus aureus. AB - Strains of Staphylococcus aureus, an opportunistic pathogen commonly found on human skin, were exposed to sunlight and UV C radiation, and the lethal and mutational effects measured. Sunlight killed cells with an inactivation constant of 3 x 10(-5) per joule per square metre; UV C was much more lethal, giving an inactivation constant of approximately 0.1 per joule per square metre. Some strains tested showed a sensitivity to sunlight that was dependent on the growth phase of the cells, exponentially growing cells showing a greater sensitivity. Mutational effects of irradiation were measured by the appearance of mutants sensitive to methicillin following irradiation of a multiresistant strain. Mutants appeared at a frequency of 10(-3); this high frequency of mutation in the region of the mec gene has also been observed when multiresistant strains are subjected to nutritional or thermal stress. Mutants showed the same chromosomal alteration (seen in pulse-field gel electrophoresis of SmaI-digested DNA) whether induced by solar or UV C irradiation. PMID- 1510558 TI - Clostridium neopropionicum sp. nov., a strict anaerobic bacterium fermenting ethanol to propionate through acrylate pathway. AB - Strain X4 was isolated several years ago from an anaerobic mesophilic plant treating vegetable cannery waste waters. It was the first example of propionic fermentation from ethanol. Morphologic and physiologic characterizations of the strain are presented here. This strain is described as type strain of a new species, Clostridium neopropionicum sp. nov. Whole cells of strain X4 ferment [1 13C] ethanol and CO2 to [2-13C] propionate, [1-13C] acetate and [2-13C] propanol, suggesting the absence of a randomizing pathway during the propionate formation. Enzymes involved in this fermentation were assayed in cell-free extracts of cells grown with ethanol as sole substrate. Alcohol dehydrogenase, aldehyde dehydrogenase, phosphate acetyl transferase, acetate kinase, pyruvate synthase, lactate dehydrogenases, and the enzymes of the acrylate pathway were detected at activities sufficient to be involved in ethanol fermentation. The same pathway may be used for the degradation of lactate or acrylate to acetate. PMID- 1510559 TI - Uptake of a fluorescent-labeled fatty acid by spiroplasma floricola cells. AB - 12-(1-pyrene)dodecanoic fatty acid (P12) uptake by Spiroplasma floricola BNR-1 cells was characterized with regard to its kinetics, specificity, metabolism and susceptibility to protein and lipid inhibitors. The uptake process depended on temperature and pH, and exhibited biphasic saturation kinetics with a very low (2.7 microM) and a high (37 microM) apparent Km value. Lauric, myristic, palmitic, stearic and oleic fatty acids did not compete with P12 for transport. The fluorescence of P12 was exclusively recovered in the neutral lipid fraction, suggesting that this fatty acid is not further utilized for phospholipid biosynthesis. Valinomycin, carbonylcyanide m-chlorophenyldrazone (CCCP), dicyclohexylcarbodiimide (DCCD), and pronase strongly reduced P12 uptake by cells, but not by membrane vesicles, affecting the high affinity (low Km) component of the uptake system. Uptake of P12 by cells, as well as by membrane vesicles, was very sensitive to glutaraldehyde, chlorpromazine, phospholipase A21 and ascorbate with FeCl3, which affected the low affinity (high Km) component of a transport system. Digitonin stimulated P12 uptake. We suggest that the incorporation of P12 into spiroplasma cell membrane is a two-step process: a high specificity energy-dependent and protease-sensitive binding to the outer surface of membrane, and a low specificity and energy-independent diffusion and partition into the membrane lipid environment. PMID- 1510560 TI - Environmental regulation of alcohol metabolism in thermotolerant methylotrophic Bacillus strains. AB - The thermotolerant methylotroph Bacillus sp. C1 possesses a novel NAD-dependent methanol dehydrogenase (MDH), with distinct structural and mechanistic properties. During growth on methanol and ethanol, MDH was responsible for the oxidation of both these substrates. MDH activity in cells grown on methanol or glucose was inversely related to the growth rate. Highest activity levels were observed in cells grown on the C1-substrates methanol and formaldehyde. The affinity of MDH for alcohol substrates and NAD, as well as Vmax, are strongly increased in the presence of a Mr 50,000 activator protein plus Mg(2+)-ions [Arfman et al. (1991) J Biol Chem 266: 3955-3960]. Under all growth conditions tested the cells contained an approximately 18-fold molar excess of (decameric) MDH over (dimeric) activator protein. Expression of hexulose-6-phosphate synthase (HPS), the key enzyme of the RuMP cycle, was probably induced by the substrate formaldehyde. Cells with high MDH and low HPS activity levels immediately accumulated (toxic) formaldehyde when exposed to a transient increase in methanol concentration. Similarly, cells with high MDH and low CoA-linked NAD-dependent acetaldehyde dehydrogenase activity levels produced acetaldehyde when subjected to a rise in ethanol concentration. Problems frequently observed in establishing cultures of methylotrophic bacilli on methanol- or ethanol-containing media are (in part) assigned to these phenomena. PMID- 1510561 TI - Distribution and immunological characterization of microbial aldehyde reductases. AB - The distribution of microbial aldo-keto reductases was examined and their immunochemical characterization was performed. p-Nitrobenzaldehyde, pyridine-3 aldehyde and ethyl 4-chloro-3-oxobutanoate reductase activities were found to be widely distributed in a variety of microorganisms. In immunodiffusion studies, most yeasts belonging to the genera Sporobolomyces, Sporidiobolus and Rhodotorula formed precipitin bands with anti-Sporobolomyces salmonicolor aldehyde reductase serum. Furthermore, the results of immunotitration experiments suggested that Sporobolomyces salmonicolor AKU 4429 contains other enzyme(s) which can reduce p nitrobenzaldehyde, pyridine-3-aldehyde and/or ethyl 4-chloro-3-oxobutanoate, and which are inactivated by anti-Sporobolomyces salmonicolor aldehyde reductase serum. PMID- 1510562 TI - Fermentative degradation of glutarate via decarboxylation by newly isolated strictly anaerobic bacteria. AB - Two strains of new strictly anaerobic, gram-negative bacteria were enriched and isolated from a freshwater (strain WoG13) and a saltwater (strain CuG11) anoxic sediment with glutarate as sole energy source. Strain WoG13 formed spores whereas strain CuG11 did not. Both strains were rod-shaped, motile bacteria growing in carbonate-buffered, sulfide-reduced mineral medium supplemented with 2% of rumen fluid. Both strains fermented glutarate to butyrate, isobutyrate, CO2, and small amounts of acetate. With methylsuccinate, the same products were formed, and succinate was fermented to propionate and CO2. No sugars, amino acids or other organic acids were used as substrates. Molar growth yields (Ys) were very small (0.5-0.9 g cell dry mass/mol dicarboxylate). Cells of strain WoG13 contained no cytochromes, and the DNA base ratio was 49.0 +/- 1.4 mol% guanine-plus-cytosine. Enzyme activities involved in glutarate degradation could be demonstrated in cell free extracts of strain WoG13. A pathway of glutarate fermentation via decarboxylation of glutaconyl-CoA to crotonyl-CoA is suggested which forms butyrate and partly isobutyrate by subsequent isomerization. PMID- 1510563 TI - The structural genes encoding CO dehydrogenase subunits (cox L, M and S) in Pseudomonas carboxydovorans OM5 reside on plasmid pHCG3 and are, with the exception of Streptomyces thermoautotrophicus, conserved in carboxydotrophic bacteria. AB - Employing deoxyoligonucleotide probes and Southern hybridizations, we have examined in carboxydotrophic bacteria the localization on the genome of genes encoding the large, medium and small subunits of CO dehydrogenase (coxL, M and S, respectively). In Pseudomonas carboxydovorans OM5 coxL, M and S were identified on the plasmid pHCG3; they were absent on the chromosome. This was evident from positive hybridizations with plasmid DNA of the wild-type strain OM5 and the absence of hybridizations with chromosomal DNA from the plasmid cured mutant strain OM5-12. The genes coxL, M and S were found on plasmids in all other plasmid-containing carboxydotrophic bacteria e.g. Alcaligenes carboxydus, Azomonas B1, Pseudomonas carboxydoflava, Pseudomonas carboxydovorans OM2 and OM4. Cox L, M and S could be identified on the chromosome of the plasmid-free bacteria Arthrobacter 11/x, Bacillus schlegelii, Pseudomonas carboxydohydrogena, and Pseudomonas carboxydovorans OM3. These results essentially confirm and extend former reports that cox genes are rather conserved among carboxydotrophic bacteria of distinct taxonomic position. However, Streptomyces thermoautotrophicus is an noteworthy exception since none of the three cox genes could be detected. This refers to a new type of CO dehydrogenase and is in accord with results indicating that the S. thermoautotrophicus CO dehydrogenase has an unusual electron acceptor specificity and some other properties setting it apart from the 'classical' CO dehydrogenases. PMID- 1510564 TI - Creatinine and N-methylhydantoin degradation in two newly isolated Clostridium species. AB - With N-methylhydantoin (NMH) as the main organic substrate, two strictly anaerobic spore forming Gram-positive bacterial strains were isolated from sewage sludge. These strains, named Clostridium sp. FS23 and Clostridium sp. FS41, totally degraded NMH, via N-carbamoylsarcosine (CS) and sarcosine as intermediates. Strain FS23 grew also with creatinine, which was converted to NMH by creatinine iminohydrolase (EC 3.5.4.21). This enzyme was formed at high rates with all substrates tested. Cytosine and 5-fluorocytosine were not utilized as substrates by creatinine iminohydrolase preparations purified to a homogeneity of 98%. NMH amidohydrolase (NMHase) and N-carbamoylsarcosine amidohydrolase (CSHase) turned out to be inducible in both strains. Other than in aerobic organisms, NMHase from these two isolated did not require ATP for enzymatic activity. SH group protecting agents were not necessary for stability. PMID- 1510565 TI - Relationship between size of parent at cell division and relative size of its progeny in Escherichia coli. AB - This article examines the empirical basis for the assumption of independence between the relative size (length or surface area) of a newborn cell w and the absolute size of its mother at cell division. Random samples from two strains of Escherichia coli B/r cells in steady-state exponential growth, covering a range of doubling times, were fixed in osmium tetroxide and prepared for electron microscopy by agar filtration. Length and diameter of over 3000 constricted cells were measured from the electron micrographs and cell surface area computed by assuming an idealized geometry of right circular cylinders with hemispherical polar caps. In general, these strains were found to divide into two daughter cells with a precision that is independent of the size of the mother. In addition, both a normal and a symmetrical beta-distribution were shown to fit the observed size distributions of w rather well; theoretical grounds for preferring the latter are discussed. PMID- 1510566 TI - Biological effects of tolytoxin (6-hydroxy-7-O-methyl-scytophycin b), a potent bioactive metabolite from cyanobacteria. AB - Tolytoxin, a macrocyclic lactone, is a potent antifungal antibiotic, exhibiting MICs in the range of 0.25 to 8 nanomolar. Tolytoxin also inhibits the growth of a variety of mammalian cells at similar doses, without specific inhibition of macromolecular synthesis. The effects in mammalian cells are primarily cytostatic, with cell death being time- and dose-dependent. Tolytoxin is highly toxic to mice, exhibiting an LD50 (ip) of 1.5 mg/kg. No antibacterial, antiviral, or hemolytic activities were observed. PMID- 1510567 TI - Characterization of urease from Sporosarcina ureae. AB - Alkaline stable (pH 7.75-12.5) urease from Sporosarcina ureae was purified over 400-fold by ion exchange and hydrophobic interaction chromatography. The cytoplasmic enzyme was remarkably active with a specific activity of greater than 9300 mumol urea degraded min-1 mg protein-1 at pH 7.5, where it has optimal activity. Although S. ureae is closely related to Bacillus pasteurii, known to possess a homopolymeric urease containing 1 nickel per subunit [M(r) = 65000], the S. ureae enzyme is comprised of three subunits [apparent M(r) = 63,100 (alpha), 14,500 (beta), and 8500 (gamma)] in an estimated alpha beta gamma 2 stoichiometry and contains 2.1 +/- 0.6 nickel ions per alpha beta gamma 2 unit as measured by atomic absorption spectrometry. Stationary phase cultures sometimes possessed low levels of urease activity, but the specific activity of cell extracts of partially purified urease preparations from such cultures could be elevated by heat treatment, dilution, or dialysis to values comparable to those observed in samples from exponentially grown cells. PMID- 1510568 TI - Studies on the effect of NAD(H) on nitrogenase activity in Rhodospirillum rubrum. AB - The effect of NAD(P) and analogs of this nucleotide on nitrogenase activity in Rhodospirillum rubrum has been studied. Addition of NAD+ to nitrogen fixing Rsp. rubrum leads to inhibition of nitrogenase. NADP+ has the same effect but NADH or analogs modified in the nicotinamide portion do not cause inhibition. In contrast to ammonium ions, addition of NAD+ leads to inhibition of nitrogenase in cells that have been N-starved under argon. The inhibitory effect of NAD+ is more pronounced at lower light intensities. Addition of NAD+ also leads to inhibition of glutamine synthetase, a phenomenon also occurring when "switch-off" is produced by the addition of effectors such as ammonium ions or glutamine. It is also shown that NAD+ is taken up by Rsp. rubrum cells. PMID- 1510569 TI - Growth yield increase and ATP formation linked to succinate decarboxylation in Veillonella parvula. AB - Veillonella parvula strain 259 (= DSM 2007) was able to grow on a mineral salts medium supplemented with (per litre) 1 g yeast extract, 1 g Tween-80, and 3 mg putrescine.2 HCl, with 6 mM thioglycolate as reductant and lactate as growth substrate. Succinate did not serve as a growth substrate, but when added in conjunction with lactate, it was decarboxylated to propionate and resulted in a measurable increase in growth yield, corresponding to the formation of 2.4 g cell dry mass per mol succinate. A growth yield increase linked to succinate metabolism occurred only while lactate was also being metabolised. Experiments with cell suspensions showed that succinate decarboxylating activity was constitutive. Addition of succinate produced clear increases in cellular ATP levels in ATP-depleted washed cells. PMID- 1510570 TI - Heterogeneity of lipoteichoic acid detected by anion exchange chromatography. AB - A complex polydispersity became apparent when the poly(glycerophosphate) lipoteichoic acid of Enterococcus faecalis was chromatographed on DEAE-Sephadex. The chain length varied between 13 and 33 glycerophosphate residues per lipid anchor. In parallel, the extent of chain glycosylation increased from 0.2 to 0.4 diglucosyl residues per glycerophosphate unit. Substitution with D-alanine ester showed a reverse distribution dropping with increasing chain length from 0.53 to 0.23 mol D-alanine per mol phosphorus. Variations in the fatty acid composition were also observed. The results extent and modify the current picture of lipoteichoic acid biosynthesis. They further suggest that during infection the mammalian organism may be confronted particularly with long-chain less hydrophobic molecular species. PMID- 1510572 TI - Energy conservation in malolactic fermentation by Lactobacillus plantarum and Lactobacillus sake. AB - A comparably poor growth medium containing 0.1% yeast extract as sole non-defined constituent was developed which allowed good reproducible growth of lactic acid bacteria. Of seven different strains of lactic acid bacteria tested, only Lactobacillus plantarum and Lactobacillus sake were found to catalyze stoichiometric conversion of L-malate to L-lactate and CO2 concomitant with growth. The specific growth yield of malate fermentation to lactate at pH 5.0 was 2.0 g and 3.7 g per mol with L. plantarum and L. sake, respectively. Growth in batch cultures depended linearly on the malate concentration provided. Malate was decarboxylated nearly exclusively by the cytoplasmically localized malo-lactic enzyme. No other C4-dicarboxylic acid-decarboxylating enzyme activity could be detected at significant activity in cell-free extracts. In pH-controlled continuous cultures, L. plantarum grew well with glucose as substrate, but not with malate. Addition of lactate to continuous cultures metabolizing glucose or malate decreased cell yields significantly. These results indicate that malo lactic fermentation by these bacteria can be coupled with energy conservation, and that membrane energetization and ATP synthesis through this metabolic activity are due to malate uptake and/or lactate excretion rather than to an ion translocating decarboxylase enzyme. PMID- 1510571 TI - Purification of a periplasmic insulin-cleaving proteinase from Acinetobacter calcoaceticus. AB - Cells of Acinetobacter calcoaceticus contain a constitutive periplasmic metalloproteinase showing similar properties as the periplasmic metalloproteinase of Escherichia coli. The periplasmic proteinase of A. calcoaceticus was purified, starting from periplasm, by ammonium sulfate precipitation, hydrophobic interaction chromatography and chromatofocusing up to the homogeneity of the enzyme in SDS-electrophoresis with a yield of 6.7% and a purification factor of 417. The enzyme has a molecular mass of 108,000 (gel filtration) or 112,000 (native electrophoresis), and consists of four identical subunits with a molecular mass of 27,000 (SDS-electrophoresis). The purified enzyme degrades preferentially polypeptides such as glucagon and insulin. Larger proteins are accepted as substrates to a considerably lower extent. All tested synthetic substrates with trypsin, chymotrypsin, elastase and thermolysin specificity were not cleaved. Therefore, the described enzyme was designated "insulin-cleaving proteinase" (ICP). PMID- 1510573 TI - Anaerobic malonate decarboxylation by Citrobacter diversus. Growth and metabolic studies, and evidence of ATP formation. AB - Citrobacter diversus ATCC 27156 was able to grow by decarboxylation of malonate to acetate under strictly anaerobic conditions, in the presence of yeast extract. The growth yield, corrected for growth on yeast extract, was 2.03 g cell dry mass per mol malonate. The addition of malonate to ATP-depleted cell suspensions (less than 0.2 nmol ATP/mg cell protein) resulted in a rapid increase in cellular ATP levels to between 4.5 and 6.0 nmol/mg cell protein. Intact cells decarboxylated malonate at rates of up to 1.5 mumol/min.mg protein. Enzyme assays on malonate grown cells indicated activation of malonate by an ATP-dependent ligase reaction and by CoA transfer from acetyl-CoA, followed by decarboxylation of malonyl-CoA to acetyl-CoA with subsequent recovery of the invested ATP by substrate level phosphorylation through the activity of acetate kinase. Net ATP synthesis is postulated to be mediated by gradient formation coupled to the decarboxylation of malonyl-CoA. The protonophore CCCP and H(+)-ATPase inhibitor DCCD significantly reduced cellular ATP levels, suggesting a role for proton gradients in the energy metabolism of this strain when growing an malonate. Inhibitors of sodium metabolism or ommission of sodium had no effect on ATP levels or malonate decarboxylation. PMID- 1510574 TI - Animal studies for prediction of chronic toxicity. PMID- 1510575 TI - Toxicological evaluation of dimethomorph: basis for assessment of risks from dietary exposure. PMID- 1510576 TI - Chronic exposure to vanadate as factor of arterial hypertension in the rat: toxicodynamic mechanisms. PMID- 1510577 TI - Medical toxicology--clinical aspects. PMID- 1510578 TI - Dermal toxicology. PMID- 1510579 TI - Cycads, designer drugs, free radicals and neurodegenerative disease. PMID- 1510580 TI - Electrophysiological and flow cytometric studies on mechanism of gentamicin nephrotoxicity in cultured renal cells. PMID- 1510581 TI - Selective cellular toxicity after exposure to 4-ipomeanol, bromobenzene (BrBz) and 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) in rat lungs. PMID- 1510582 TI - Decreased hepatic phosphoenolpyruvate carboxykinase gene expression after 2,3,7,8 tetrachlorodibenzo-p-dioxin treatment: implications for the acute toxicity of chlorinated dibenzo-p-dioxins in the rat. AB - Decreased activity of the rate limiting gluconeogenic enzyme, phosphoenolpyruvate carboxykinase (PEPCK), has been recently suggested to be the critical lesion in the acute toxicity of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). We now show that other toxicologically relevant chlorinated dibenzo-p-dioxins (CDDs), with chlorine substituents in the crucial 2-,3-,7-, and 8-positions, exert the same effect on PEPCK activity. The doses required to cause this enzyme inhibition are within the acutely toxic range for each homologue, suggesting the same mechanism of action for these compounds. To further investigate the mechanism whereby dioxins decrease PEPCK activity, Northern analysis was performed using a cDNA probe complementary to a portion of the PEPCK mRNA. We could demonstrate that after TCDD treatment hepatic PEPCK mRNA was decreased by as much as 90% compared to pair-fed control animals (day 8 after dosing). This decrease in PEPCK mRNA was paralleled by a decrease of the amount of PEPCK protein and enzymatic activity. These results indicate that the physiological changes which occur in TCDD-treated animals (decreased feed consumption, low plasma insulin and elevated plasma corticosterone levels) which under normal conditions increase PEPCK gene expression and enzyme activity, are not effective in stimulating PEPCK synthesis in TCDD-treated animals. PMID- 1510583 TI - Co-cultures of rat hepatocytes in the study of valproate toxicity. PMID- 1510584 TI - Selenium-silver interaction in mice. PMID- 1510585 TI - Environmental impact on domestic and wild animals: field data from a veterinary anti-poison center. PMID- 1510586 TI - Blood mercury and serum selenium concentrations in reindeer herders in the arctic area of northern Finland. AB - 163 healthy reindeer herders living in the arctic area of northern Finland were investigated for blood mercury and serum selenium concentrations. More than ten percent of the subjects had blood mercury above the upper normal limit. High organic and total organic mercury levels were most common in the northeastern part of the country. High organic and total mercury and selenium values were more common in the Lapps than the Finns. Blood mercury levels increased with increasing fish consumption. The pollution in the northeastern part of this country probably leads to the increased formation of organic mercury, and its enrichment in the food chain. The association of high selenium with high mercury probably reduces the toxicity of the latter. PMID- 1510587 TI - Natural syndromes in dogs. PMID- 1510588 TI - Inducible thyroid lesions in the rat with special reference to mediation or interactions with other organ systems. PMID- 1510589 TI - Research aspects in clinical toxicology. PMID- 1510590 TI - Variations in prevalence of endocrine tumors among different colonies of rats? A retrospective study in the Hannover registry data base. AB - Illustrated by data derived from the endocrine system it could be demonstrated that at least the following requirements have to be fulfilled when using historical control data for the interpretation of animal studies: The main and basic requirement is the utilization of standardized diagnostic criteria and a systematized nomenclature for all data which should be compared. This includes the historical control data as well as histopathological diagnoses obtained from other animal studies. All findings stored in the REGISTRY are based on standardized criteria and this nomenclature was also applied for the more recent studies which were evaluated by pathologists of the member companies. Data from literature which are frequently used for comparison and interpretation cannot always fulfill this requirement due to the variation of diagnostic criteria used by different investigators. The second important requirement is an exact knowledge of study-related details. Some dependencies of the tumor rate on the sex, the strain, the breeder and the age were shown in a few examples. But other parameters, like diet, caging, bedding etc. may also influence the frequency of spontaneously occurring tumors and therefore have to be taken into account. In the REGISTRY such data from routine carcinogenicity and toxicity studies are available because all these studies are performed under GLP conditions and all parameters are carefully recorded. During the relatively short period of its activity, the REGISTRY has become not only source of historical laboratory data, but also it subserves as indispensable tool of quality control warranted by peer review effects of panel meetings. An additional benefit will emanate from the data base in the near future: Exact knowledge of the magnitude of the influence of distinct parameters will enable the member companies to use the information for the design or optimization of new studies, as well as to extend the analysis and support the interpretation of observed results. PMID- 1510591 TI - Biologically based modeling in toxicology research. AB - Biologically based modeling can be described as the process by which the specific mechanistic steps governing tissue disposition and toxic action of chemicals are expressed in quantitative terms by a set of equations leading to prediction of the outcome of specific toxicological experiments by computer simulation. These models are useful in risk assessment because their mechanistic biological basis permits the high-to-low dose, route to route and interspecies extrapolation of the tissue disposition and toxic action of chemicals. By far their greatest utility is not as "finished" risk assessment models, but as research tools that convey a quantitative expression of our hypotheses of tissue disposition and toxic action of a chemical. A structured modeling approach to toxicology problems helps identify the data gaps in the areas of chemical disposition and toxic action, thus prioritizing on-going research to obtain critical information required to conduct quantitative risk assessment. This paper examines progress in developing comprehensive biologically based models for cancer induction by non genotoxic carcinogens that are cytotoxic in target tissues. The strategies for linking the models on dosimetry, cytotoxicity, and carcinogenicity are described in detail. The basic concepts and approaches discussed here can be applied to many other toxic chemicals and to toxicity endpoints other than cancer. PMID- 1510592 TI - QSAR studies in genetic toxicology: congeneric and non congeneric chemicals. PMID- 1510593 TI - Quantitative and qualitative structure activity relationships in developmental toxicity. PMID- 1510594 TI - Multi-compartment model to study the effect of air-blood and blood-tissue partition coefficients on concentration-time-effect relationships. AB - The influence of the air-blood (lambda) and blood-tissue partition coefficients of substances on the concentration-time-effect relationship E = [aCnT]b was studied by model simulation of uptake and distribution of gases. The model consisted of a lung compartment and four tissue compartments. Rat and human model parameters were obtained from physiological data, and substance-dependent variables. The observable effect E (righting reflex, mortality, etc.) for directly acting systemic agents was supposed to be related to the (arbitrarily chosen) concentration of the substance in the arterial blood or in the liver compartment. We conclude that for a directly acting systemic agent n greater than or equal to 1. If n less than 1 other mechanisms such as metabolism must be incorporated in the model which, however, should not be excluded when n greater than or equal to 1. If the observable effect is related to arterial concentration of the substance, n increases with decreasing lambda. If the liver concentration is related to the observable effect, man and rat may behave quite differently. This has major consequences for the extrapolation of animal results to the human situation in risk assessment. PMID- 1510595 TI - Concepts for toxicokinetic-toxicodynamic modelling in clinical toxicology: application to acute cardiac glycoside intoxications. PMID- 1510596 TI - Analytical forensic toxicology. PMID- 1510597 TI - Biological effect monitoring. PMID- 1510598 TI - Biological monitoring of exposure to bitumen fumes during road paving operations. PMID- 1510599 TI - Toxicological investigations on unusual materials (hair and vitreous humor): interest and limitations. PMID- 1510600 TI - Ethylene oxide: metabolism in human blood and its implication to biological monitoring. PMID- 1510601 TI - Diagnosis in clinical toxicology. PMID- 1510602 TI - Medical toxicology in Europe: present and future. PMID- 1510603 TI - Haemoperfusion, indications and side-effects. PMID- 1510604 TI - Accidental poisoning with hydrocarbon products in children during six months 1989. PMID- 1510605 TI - Clinical neuropsychological assessment of patients chronically exposed to organic solvents. PMID- 1510606 TI - Risk assessment--scientific aspects. PMID- 1510607 TI - Industrial aspects of risk assessment. PMID- 1510608 TI - Risk assessment: governmental aspects. PMID- 1510609 TI - Communicating about toxicological risks. PMID- 1510610 TI - Health risk assessment of long term exposure to chemicals: application to cadmium and manganese. PMID- 1510611 TI - [Immunologic reaction and ventilatory function in hemp-processing workers]. AB - The relationship between immunological status and respiratory function was studied in 42 hemp workers and in 49 control workers. The highest prevalence of positive skin tests was recorded for a mixture of hemp and flax (64%), followed by flax (48%), hemp on a combining machine (41%), hemp on a carding machine (38%), hemp on spinning and weaving machines (33%), and hemp on a softening machine (20%). The prevalence of positive skin tests in control workers was smaller and varied from 21 to 5%. Increased IgE was found in 35.7% of the hemp workers and in 5.0% of the controls (P less than 0.05). Hemp workers with positive skin tests had a significantly higher prevalence of chronic respiratory symptoms than those with negative skin tests. Acute ventilatory capacity reductions did not differ in respect to the immunological status. An extract of hemp dust caused a constriction of an isolated guinea pig tracheal smooth muscle in vitro. Our data suggest that hemp dust as well as producing an immunological effect may exert an irritant effect on the respiratory system in exposed textile workers. PMID- 1510612 TI - [Isoproterenol toxicity in the myocardium in an experiment]. AB - The effect of toxic doses of isoproterenol (ISP) on total activities and isoenzyme patterns of creatine kinase (CK) and lactate dehydrogenase (LDH) in rat sera was investigated and correlated with histopathological changes in the myocardial tissue. A single dose of 25 mg ISP per 100 g body weight caused a statistically important elevation of CK and LDH total activities and of the activities of cardiospecific isoenzymes CK-MB, LDH-1 and LDH-2 six hours after intraperitoneal administration. The isomorphic LDH isoenzyme pattern, which was also observed, was taken to be a proof of the ISP-induced cardiogenic shock. The increase in the activity of CK-MM and LDH-5 isoenzymes could be explained as a secondary consequence of cardiogenic shock and of the consecutive damage of the tissue with anaerobic metabolism such as liver. The findings were confirmed by a histopathological analysis showing the development of coagulative necrosis and myocytolysis as well as undulations of heart muscle cells as a sign of cardiogenic shock. PMID- 1510613 TI - [Xenobiotic and biochemical parameters of isolated rat hepatocytes]. AB - The authors investigated the effects of the inductors (griseofulvin and fenitoin) and the inhibitors of the cytochrome P-450 (metronidazole, chloramphenicol and phenylbutazone), the effects of the drugs with the purine structure (aminophylline, xanthinol-nicotinate, pentoxiphylline, azathioprine, thioguanine, 6-mercaptopurine), and the effects of several pesticides (lindane, binapicrile, parathion) on some biochemical parameters of the rat liver. The following parameters were determined: viability of hepatocytes, the content of glutathione and cytochrome P-450, and the activity of xanthinoxidase and lipoperoxidase. The experiments were performed in vivo and in vitro. The results showed that the cell viability as well as the other parameters studied, were most drastically affected by chloramphenicol, azathioprine and parathion, whereas the other substances elicited less intensive changes. PMID- 1510614 TI - [Cytogenetic changes in persons exposed to polychlorinated biphenyls]. AB - A cytogenetic study performed in a group of workers exposed to polychlorinated biphenyls comprised analysis of structural chromosomal aberrations in the lymphocytes in the first division in vitro, analysis of micronuclei frequency in binuclear lymphoblasts induced by cytochalasin B and analysis of sister chromatid exchanges. The study included 48 exposed workers and 15 controls. In 16 exposed workers increased incidence of unstable chromosomal aberrations (dicentrics, rings and acentrics) was found, while in 19 no structural chromosomal aberrations could be detected. In 11 workers changes defined as chromosomal and chromatid breaks were noted. This type of change, however, can be evidenced in a non exposed population as well. In two workers stable chromosomal aberrations were recorded (translocations and inversions). The incidence of micronuclei as well as exchange of sister chromatids were elevated in the exposed group of workers compared to controls. PMID- 1510615 TI - [The effect of occupational noxae in the tobacco industry on pulmonary function in exposed workers]. AB - A study was carried out to determine respiratory hazards to workers in tobacco manufacture. The investigations at the workplace included analysis of the work technology and measurements of chemical pollutants and dust concentrations in the work rooms. Ventilatory lung function tests were performed in 95 workers exposed to tobacco dust and in 129 control workers. Results of workplace analysis showed the presence of tobacco dust levels exceeding the maximum permissible concentrations. The values of some lung function tests for exposed workers non smokers were significantly lower than for control workers non-smokers. They could be attributed to the effect of occupational noxae on the respiratory system. PMID- 1510616 TI - [Epidemiologic and sociologic aspects of occupational bronchial asthma]. AB - The main problems confronted in epidemiological investigations of occupational bronchial asthma are described, such as the absence of a definition of the disease, the need for a standardized questionnaire for the symptoms of the disease and the heterogeneity of the functional lung tests. The questionnaires most frequently used for respiratory symptoms and the most suitable tests for measuring and evaluating ventilatory lung function are discussed. The problem of identifying the persons who are at risk of developing occupational bronchial asthma is also dealt with. PMID- 1510617 TI - [Psychological methods in the evaluation of neurotoxic effects of organic solvents]. AB - Organic solvents comprise a large and heterogenous group of chemical compounds and mixtures, largely belonging to volatile hydrocarbons. They are widely used in various industries. Long-term exposure to organic solvents as a cause of the central nervous system impairement has been subject of extensive epidemiological and clinical studies for years, especially in Scandinavia, but often with inconsistent results. In 1985 the World Health Organization published the criteria for the evaluation of neurotoxic effects of solvents that are now commonly accepted. The present paper provides a short review of the current state of knowledge in the field emphasizing the role of neuropsychological methods in assessing solvent toxicity. PMID- 1510618 TI - Spatula test for fracture of mandible. PMID- 1510619 TI - Warfarin anticoagulation. PMID- 1510620 TI - Hip pain in children. AB - Children who present with a limp and pain in the hip, anterior thigh and the knee can have a serious disorder of the hip. The age at presentation tends to provide a guide to the possible problem, such as a slipped upper femoral epiphysis and a stress fracture of the femoral neck in adolescents. PMID- 1510621 TI - Patient education. Endometriosis. PMID- 1510622 TI - Miserables. PMID- 1510623 TI - Diagnosing HIV infection. PMID- 1510624 TI - Less confusion in the ranks. PMID- 1510625 TI - Sleep laboratories from a neurological perspective. PMID- 1510626 TI - Testing innovations in health care. PMID- 1510627 TI - Augmentation mammaplasty. PMID- 1510628 TI - Cosmetic surgery for the ageing face. AB - Cosmetic surgery is unique in that the results are qualitative. Recent technical advances now allow the skilled and artistic surgeon to achieve the degree of change requested by most patients, without the obvious operated look. General practitioners should extend their professional relationship with cosmetic surgery patients. Preliminary counselling can reduce patient's anxiety by clarifying their objectives and by providing relevant information and support. The relationship of trust so engendered is helpful for post operative support and allows the practitioner to share in the satisfaction experienced by the patient as a result of surgery. PMID- 1510629 TI - The injured hand. AB - Careful evaluation and diagnosis of the injured hand, with appropriate early treatment, can reduce the morbidity of a hand injury substantially. Aim for uncomplicated primary healing of injured structures, keeping oedema, inflammation and subsequent scar immobility to a minimum. If the repair is beyond your surgical skills or experience--refer early. PMID- 1510630 TI - Common pitfalls in plastic surgery from the GP perspective. AB - General practitioners are responsible for the overall management of patients and their expertise is invaluable in this respect. With the ever changing horizons in disease processes and therapeutics, the dedicated family physician has more knowledge in general than many of his specialist colleagues. It is unfair, however, to expect general practitioners to have an in-depth knowledge of all conditions. These notes, I believe, offer family practitioners some beneficial information on possible pitfalls. My plastic surgeon colleagues would agree, I am sure, that further advice on any dilemma is merely a telephone call away. PMID- 1510631 TI - Recent advances in plastic surgery. AB - Scarless healing and the creation of like-tissue for reconstruction have been the aims of plastic surgery since its inception. Recent advances bring us even closer to the ideal. PMID- 1510632 TI - Liver transplantation in the 1990s. AB - Liver transplantation is now the therapy of choice for advanced, irreversible, progressive liver disease. The authors look at who should have a transplant and explain that the predicted outcomes of surgery depend on the pre-operative disease. A brief overview of post-operative care is given. PMID- 1510633 TI - Barriers to cervical screening in older women. AB - OBJECTIVE: To explore the reasons why some older women do not have regular Papanicolaou smear tests. SETTING: The Ballarat region of Victoria. DESIGN AND METHOD: Cross-sectional survey administered by telephone interview. SAMPLE: Three hundred and forty-seven women aged 40 to 70. RESULTS: 1. 41% of women had not had a Papanicolaou smear test within the preceding 2 years. 2. Women who agreed with the statement that healthy women do not need to have Papanicolaou tests were six times more likely to be overdue for a Papanicolaou test than women who did not agree. 3. Being over 60 significantly increased the likelihood that a woman would be overdue for a Papanicolaou test, compared with younger women. 4. Women who thought that the test is only needed at intervals of 3 years or more were over six times more likely to be overdue than women who believed the interval to be 2 years or less. 5. Women who perceived themselves as being too embarrassed were nearly seven times more likely to be overdue than women who claimed no embarrassment. 6. Women who saw themselves as being too busy to have the test were three times more likely to be overdue than women who did not see themselves this way. 7. Women with a spouse were less likely to be overdue than other women. 8. Women who knew to start having Papanicolaou tests when they were sexually active were less likely to be overdue than women who did not know this. CONCLUSION: Many of these barriers can be overcome by the clinician in routine practice. PMID- 1510634 TI - Nail avulsion by chemolysis. PMID- 1510635 TI - Charles Bridges-Webb. Academic general practitioner and epidemiologist. PMID- 1510636 TI - Miscellaneous (Part 1). PMID- 1510637 TI - The effect of trans-cockpit authority gradient on Navy/Marine helicopter mishaps. AB - Navy and Marine Corps helicopter mishaps which had a pilot causal factor assigned were examined to determine if the relative military rank of the pilot and copilot was associated with the rate of occurrence per 100,000 flight hours. All class A and B helicopter flight mishaps for the 11 calendar year period 1980-1990 were examined. Although no statistically significant differences were noted, pairing pilots who were of equal rank yielded the lowest rate, seemingly refuting Elwyn Edward's notion that a flat "trans-cockpit authority gradient" may lead to greater problems in the cockpit than his hypothetical "optimum gradient." Moreover, when copilots flew with pilots who differed by two or more ranks, the largest pilot error rate was revealed. This last finding seems to support Edward's hypothesis that a steep "trans-cockpit authority gradient" may be detrimental to aviation safety. PMID- 1510638 TI - Cardiovascular responses to positive pressure breathing using the tactical life support system. AB - The improved protection afforded by the Tactical Life Support System (TLSS) vs. other partial pressure ensembles has not been reported with respect to the cardiovascular effects of positive pressure breathing (PPB). Nine seated subjects wearing TLSS were exposed to 30, 50, and 70 mm Hg PPB (breathing air) with four times this pressure in the G-suit. Experiments were conducted at ground-level in order, separated by 4 min rest and preceded by a 1-min control period. Stroke volume and cardiac output (SV, CO) and indexes (SI, CI) were determined by impedance cardiography. Mean arterial pressure (MAP) was directly related to PPB level, increasing by 23%, 32%, and 47% for each PPB level, respectively (p less than 0.01). HR, SV, and CO were unaffected after 4 min of 30, 50, and 70 mm Hg PPB. The results indicate that cardiovascular function decay is less severe than that reported using other PPB ensembles at similar PPB levels. Improved protection is most likely due to the greater pressurization of the G-suit and the 45% greater bladder volume in the leg bladders, leading to restored venous return and SV. PMID- 1510639 TI - Maximum intra-thoracic pressure with anti-G straining maneuvers and positive pressure breathing during +Gz. AB - Positive pressure breathing during +Gz (PBG) and anti-G straining maneuvers (AGSM) each improve +Gz tolerance by increasing blood pressure through increases in intra-thoracic pressure, but the maximal intra-thoracic pressure from their combined effect is not known. Six subjects performed the following: 1) maximal AGSM at +1 Gz; 2) assisted PBG (constant 60 mm Hg) at +Gz; 3) submaximal AGSM at +Gz (enough to maintain peripheral vision); 4) maximal AGSM at +Gz; and 5) combined PBG and maximal AGSM at +Gz. They wore TLSS mask/helmet ensemble, CSU 15/P G-suit, and TLSS-style jerkin. Intra-thoracic pressure was measured with a catheter-tip pressure transducer in the esophagus (Pes). The change in gastric pressure was also measured (delta Pga). For both Pes and delta Pga, there were no significant differences among experimental conditions (1), (4) and (5), as above. Group mean Pes and delta Pga in these three conditions were 139 and 197 mm Hg, respectively. The similar results between maximal AGSM, and maximal AGSM and PBG are explained by limited support from the thoracic counter-pressure garment, and the characteristics of the respiratory system. PMID- 1510640 TI - Adaptations to unilateral lower limb suspension in humans. AB - This study examined the effect of unilateral lower limb suspension (ULLS) on neuromuscular function in humans. Eight subjects (31 +/- 4 years old) performed all ambulatory activity on crutches for 6 weeks while wearing a shoe with a 10-cm sole on the right foot to unweight the left lower limb. Knee extensor (KE) torque during eccentric, concentric, and isometric actions, and electromyography (EMG) of m. vastus lateralis (m. VL), m. gastrocnemius medialis (m. GM) and m. soleus (m. SL) during isometric actions were assessed pre-ULLS, post-ULLS, and after 4 d of recovery. Average muscle cross-sectional area (CSA) of the KE was measured pre and post-ULLS and that of the ankle extensors (AE) post-ULLS using magnetic resonance imaging. Strength of the KE of the suspended left limb was reduced (p less than 0.05) 21 and 15%, respectively, after ULLS and 4 d later. Average muscle CSA of the left KE decreased (p less than 0.05) 16%. The KE of the non suspended right limb showed no changes in muscle CSA. Thus, average muscle CSA of the KE of the suspended limb was 17% less (p less than 0.05) than that of the non suspended limb. Average muscle CSA of the AE, likewise, was smaller (18%, p less than 0.05) in the left than right leg after ULLS. Maximal integrated EMG of VL and overall mean power frequency of GM and SL for submaximal isometric actions were both decreased (p less than 0.05) post-ULLS.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1510641 TI - Exercise performance, core temperature, and metabolism after prolonged restricted activity and retraining in dogs. AB - To study physiological effects of restricted activity (RA) and subsequent retraining, 10 male mongrel dogs (1-5 years) performed a submaximal exercise endurance test on a treadmill (12 degrees slope, 1.6 m.s-1) during kennel control, after 8 weeks of cage (40 cm-w x 80 cm-h x 110 cm-l) confinement, and after 8 weeks of retraining using the same treadmill protocol 1 h/d for 6 d/week. Compared with control endurance (172 +/- 19 min), endurance decreased to 102 +/- 15 min (delta = -41%, p less than 0.05) after RA and increased to 223 +/- 24 min (delta = +30%, p less than 0.05) after training: the respective final levels and changes in rectal temperature were 41.25 and +2.15 degrees C, 41.60 and +2.70 degrees C (NS), and 41.35 and +2.40 degrees C (NS), respectively. Resting and post-exercise blood glucose and lactate concentrations were unchanged in the three experiments. After RA, resting muscle glycogen was reduced from a control level of 49.9 +/- 4.3 to 34.1 +/- 4.5 mmol.kg-1 (delta = 32%, p less than 0.05) which returned to the control level of 58.4 +/- 3.5 mmol.kg-1 after retraining. Resting plasma FFA levels were unchanged, but the RA post-exercise change was decreased from a control level of +0.400 +/- 0.099 to +0.226 +/- 0.039 mmol.L-1 (p less than 0.05). Neither restricted activity nor training affected glucose tolerance significantly. The results indicated that RA reduces exercise endurance, the effectiveness of exercise thermoregulation, muscle glycogen stores, and the lipolytic response to exercise and to noradrenaline stimulation. All these changes were reversed following 8 weeks of retraining. PMID- 1510642 TI - Influence of self-induced hypnosis on thermal responses during immersion in 25 degrees C water. AB - The efficacy of self-induced post-hypnotic suggestion to improve thermogenic responses to head-out immersion in 25 degrees C water was evaluated in 12 males. An on-line computerized system permitted the change in body heat storage to be used as the independent variable and immersion time as the dependent variable. Test-retest reliability was good, exhibiting a coefficient of variation of less than 5% for exposure time. Immersion profiles consisted of the following: rest until 200 kJ of heat were lost, leg exercise at VO2 approximately 1.5 L.min-1 to regain 200 kJ, rest until 100 kJ were lost, and repeat the exercise to regain 100 kJ. A control immersion was done prior to two 1-h hypnotic training sessions. A second immersion (hypnotic) occurred within 24 h after training. There were no differences in rates of heat production, heat loss, mean skin temperature, or rectal temperature between control and hypnotic immersions. Individual hypnotic susceptibility scores did not correlate with changes in thermal status. Ratings of perceived exertion during exercise were similar for both immersions, but perceived sensation of cold was lower during the second rest period of the hypnotic immersion. Three subjects used images of warm environments during their hypnotic immersion and lost heat at a faster rate than during control immersions. These results indicate that brief hypnotic training did not enhance the thermogenic response to cool water immersion. PMID- 1510643 TI - Effect of high terrestrial altitude and supplemental oxygen on human performance and mood. AB - Sustained exposure to high terrestrial altitudes is associated with cognitive decrement, mood changes, and acute mountain sickness (AMS). Such impairment in aviators could be a safety hazard. Thirteen male soldiers, ages 19-24, ascended in 10 min from sea level to 4,300 m (simulated), and remained there 2.5 d. Four times per day, subjects completed a test battery consisting of nine cognitive tests, a mood scale, and an AMS questionnaire. During one test session per day, subjects breathed 35% oxygen instead of ambient air. Analysis revealed transient deficits on altitude day 1 for three cognitive tasks. Most tasks displayed a persistent training effect. Sick subjects' moods were more negative and their performance improvement less. On altitude day 1, oxygen administration improved performance on two cognitive tests and one mood subscale. Following rapid ascent to 4,300 m, performance is most affected during the first 8 h. Individuals affected by AMS tend to improve more slowly in performance and have more negative moods than those who feel well. PMID- 1510644 TI - Emesis in ferrets following exposure to different types of radiation: a dose response study. AB - Ferrets were exposed to gamma rays (60Co), fission neutrons, high-energy electrons (18.5 MeV) or iron particles (56Fe, 600 MeV/amu) in order to establish the dose-response relationships for emesis following exposure to different types of radiation. The results showed that the mean effective doses (ED50s) for iron particles (35 cGy) and neutrons (40 cGy) were similar. High-energy electrons were the least effective radiation, with an ED50 of 138 cGy. Gamma rays, with an ED50 of 95 cGy, showed an intermediate effectiveness. The results suggest that the relative effectiveness of different types of radiation generally increases with an increase in linear energy transfer (LET), although LET is not completely predictive of relative behavioral effectiveness. PMID- 1510645 TI - The effect of captopril on +Gz tolerance of normotensives. AB - Recently, there has been considerable interest in whether angiotensin converting enzyme inhibitors can be used to treat hypertensive pilots without compromising their operational effectiveness. This study was undertaken to evaluate the possible effects of captopril on tolerance to +Gz, of relevance in tactical fighter operations. A counterbalanced double blind crossover protocol was used to administer 25 mg of captopril or placebo twice daily in identical capsules to seven fit, normotensive individuals from the DCIEM acceleration research panel. The five males and two females took each course of capsules for 4 d prior to G tolerance assessment and waited 1 week for drug wash-out after assessment on their first condition prior to commencement of the second course of capsules. The subjects did not wear G-suits. Standard ASCC gradual onset runs, relaxed and with a straining maneuver, and rapid onset runs were used to assess G tolerance. The group G tolerances are listed as mean +/- S.E.M.: during relaxed gradual onset runs (GOR) 3.96 +/- 0.14 on placebo and 3.61 +/- 0.10 on captopril (p = 0.02, paired t-test). Corresponding results for relaxed rapid onset runs (ROR) were 3.36 +/- 0.17 on placebo and 3.33 +/- 0.18 on captopril (p = 0.21, Wilcoxon signed ranks test). The straining tolerances during GOR runs were 7.21 +/- 0.23 on placebo and 6.83 +/- 0.25 while on captopril (p = 0.05, paired t-test). Given the relatively low dosage and the significant compromise of Gz-tolerance on both relaxed and straining GOR runs, caution is recommended in using captopril to treat hypertensive fighter aircrew.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1510646 TI - Effect of Gz forces and head movements on cervical erector spinae muscle strain. AB - A portable surface-integrated EMG (IEMG) device was used to investigate the strain caused by low and high Gz forces and head movements on the cervical erector spinae muscles during flight missions. The obtained IEMG activities were normalized by comparing them with activities representing maximal voluntary contraction (MVC) of the cervical erector spinae muscles in each subject. The muscular strain increased with increasing Gz forces and head movements. Under +7.0 Gz the mean muscular strain was 5.9-fold compared with +1.0 Gz and was 37.9% of the MVC. In some individuals, the muscular tolerance (100% of the MVC) was ipsilaterally reached already under +4.0 Gz with concomitant movements and twisted positions of the head. Pilots are susceptible to acute neck injury when the protection afforded by their neck muscles is insufficient. PMID- 1510647 TI - Treatment of acute diarrhea with norfloxacin during Desert Storm deployment. AB - A retrospective study on the treatment of diarrhea in a U.S. Air Force Wing deployed to Egypt during Operation Desert Storm was conducted. Two groups of patients were compared for treatment efficacy. One group was treated with norfloxacin 800 mg as a single dose with the onset of symptoms. The other group was treated conservatively. The group treated with norfloxacin was noted to become asymptomatic in one-fourth the time of the group treated conservatively. This was highly significant, statistically, and in practice. It is recommended that diarrhea be treated aggressively during deployments to third world countries. PMID- 1510648 TI - Crewmember communication in space: a survey of astronauts and cosmonauts. AB - A total of 54 astronauts and cosmonauts returned questionnaires which addressed various aspects of crewmember communication in space. All respondents believed that crewmembers should be fluent in one shared common language, but American and Soviet space travelers were less tolerant of dialect differences than their international counterparts. Sensory activities (Watching and Listening) were rated as significantly increasing in space, whereas more complex communicative activities (Reading, Gesturing, and Writing) were judged to significantly decrease. Cosmonauts scored higher than astronauts in all verbal and nonverbal activities, possibly reflecting more responsiveness to the space environment. Several factors were rated as significantly helping intracrew communication: Shared Experience, Excitement of Space Flight, Close Quarters, and Isolation from Earth. Other factors were judged to significantly hinder communication: Facial Swelling, Spacecraft Ambient Noise, and Space Sickness. These findings have important operational and scientific implications involving future manned space missions. PMID- 1510649 TI - Injuries associated with the use of ejection seats in Finnish pilots. AB - During the years 1958-91 17 Finnish pilots were forced to use ejection seats. The aircraft types were as follows: a) BA Hawk in 6 instances; b) a Mig 21-F-13 in 4; c) a Mig-21-Bis in 3; d) a Gnat Folland in 2; e) a Vampire Trainer in 1; and f) a MU-3 in 1 case. There were 3 ejections completed successfully, 12 pilots sustained slight injuries, and 5 pilots suffered major injuries--3 from compression fractures of the thoracic spine, 1 from fracture of the femur, and 1 from rupture of the medial collateral ligament of the knee. All major injuries were associated with Soviet aircraft. One BA-Hawk pilot died due to a direct impact against a tree after a low-altitude ejection. Two pilots launched the seat under negative G-forces. One of these became temporarily blind, and suffered a partial loss of vision for 3 months. Four Hawk pilots were saved during landing phase by a tandem ejection, receiving only minor injuries. PMID- 1510650 TI - Malcolm Grow and the Russian connection. PMID- 1510651 TI - Peacetime U.S. Army air-crew rescue and factors delaying rescue. PMID- 1510652 TI - Peacetime U.S. Army air-crew rescue and factors delaying rescue. PMID- 1510653 TI - Air-to-air target detection. PMID- 1510654 TI - The origin of the electrophoretic doublet of thyroglobulin. AB - Bovine and human thyroglobulin show two closely migrating bands in reducing SDS PAGE. Limited digestion with chymotrypsin, trypsin and thermolysin converted the slower band of the doublet into a peptide identical to the faster band, with an apparent mass of 270 kDa, in both species. The starting point of the faster band of the doublet was established at Ileu 520 with native bovine Tg and at Ser 503 with native human Tg, and at Ser 503 and Ser 504 with chymotrypsin-digested bovine and human Tg, respectively. These data explain the electrophoretic heterogeneity of thyroglobulin and unveil a region highly susceptible to proteolysis at about 500 residues from the NH2-terminus of the molecule. PMID- 1510655 TI - Neurocalcin, a novel calcium binding protein with three EF-hand domains, expressed in retinal amacrine cells and ganglion cells. AB - Neurocalcin (molecular weight 23,000 and 24,000) is a newly identified Ca2+ binding protein with three EF-hand domains and has a strong amino acid sequence homology with visinin and recoverin (Terasawa, M., Nakano, A., Kobayashi, R., and Hidaka, H. J. Biol. Chem. In press). We produced antibody against neurocalcin. Immunoblotting showed the presence of neurocalcin in bovine retina as well as brain, suggesting that neurocalcin was a neuron specific Ca2+ binding protein. Immunohistochemistry revealed the expression of neurocalcin in retinal amacrine cells and ganglion cells but not in the photoreceptor layer. This distribution of neurocalcin was quite different from that of visinin and recoverin. Our results suggest that neurocalcin may play an important role in a Ca2+ signal pathway of the nervous system. PMID- 1510656 TI - Propagation of a calcium pulse between osteoblastic cells. AB - Using rat calvaria cells in primary culture monolayers and bone-like nodules, and isolated rat osteosarcoma cells, we show via laser scanning confocal microscopy and fluorescent indicator fluo-3/AM, that mechanical perturbation of a cell results in a transient increase (pulse) of measured intracellular calcium concentration that propagates from cell to cell, even between cells connected only by a thin process. The calcium pulse does not occur in the mechanically perturbed cell in calcium-free bathing medium, nor is there pulse propagation under this condition. Halothane, which blocks gap junctions, inhibits propagation. Propagation velocity does not decrease with successive cell to cell steps. These observations suggest the existence of a self-regenerating calcium signaling mechanism that may be based on a form of calcium-induced calcium release. PMID- 1510657 TI - Reactive oxygen-reducing and protein-refolding activities of adult T cell leukemia-derived factor/human thioredoxin. AB - Reducing and protein-refolding activities of adult T cell leukemia-derived factor (ADF)/human thioredoxin were studied. Recombinant ADF/human thioredoxin produced by E. coli, which has an insulin-reducing activity as efficient as that of E. coli thioredoxin, also reduced some reactive oxygen species, such as hydrogen peroxide. Furthermore, recombinant ADF/human thioredoxin was found to have protein-refolding activity for scrambled (mispaired disulfide-containing) RNase A. Cys-31 at the active site of ADF/human thioredoxin proved essential for reducing activity, and loss of Cys-31 in ADF/human thioredoxin attenuated the protein-refolding activity. These data suggest a physiological role of ADF/human thioredoxin in protecting living cells from proteotoxicity caused by reactive oxygens in vivo. PMID- 1510658 TI - Evaluation of the holoenzyme content of aromatic L-amino acid decarboxylase in brain and liver tissues. AB - We have re-evaluated the content of the holo-form of aromatic L-amino acid decarboxylase in rat tissues. Aromatic L-amino acid decarboxylase was found to consume pyridoxal 5'-phosphate while it underwent decarboxylation-dependent transamination as a side reaction. We observed that the total dopamine formation was proportional to the amount of holoenzyme. Dopamine formation in a tissue extract, which was preincubated with pyridoxal 5'-phosphate, was compared with the same tissue sample but which was prepared without preincubation. Percentages of holo-form of aromatic L-amino acid decarboxylase obtained from such comparison were 78% for brain and 94% for liver tissues. These values were significantly higher than those reported earlier in which the decarboxylation-dependent transamination of the decarboxylase had been overlooked. PMID- 1510659 TI - Augmented expression of HSP72 protein in normal human fibroblasts irradiated with ultraviolet light. AB - Normal human fibroblasts synthesized heat shock protein (HSP) 72 constitutively and its expression was augmented 6 hours after UV irradiation. Maximum induction of HSP72 was obtained at 12 hours and HSP72 showed a punctuated distribution in nucleus. While unscheduled DNA synthesis was almost completed 12 hours after UV irradiation, the S phase fraction decreased immediately and recovered after 6 hours. Thus, HSP72 augmentation was occurred coincidentally with the recovery of S phase, and suggested that HSP72 had some function during the recovery of DNA replication inhibited after UV irradiation. PMID- 1510660 TI - The characterization of 5 histidine-serine mutants of human 5-lipoxygenase. AB - The physical and catalytic properties of 5 histidine-serine mutants of human 5 lipoxygenase (5-LO) have been characterized. The mutants HS363, HS391 and HS400 have activities, pH optima and stabilities similar to those of the wild type enzyme. The iron content of each of these mutants is 0.30-0.53 mol Fe/mol 5-LO which is within the range observed for the wild type enzyme. HS368 contains iron (0.15 and 0.43 mol Fe/mol 5-LO in 2 preparations) but has no detectable oxygenase, leukotriene A4 synthase or anaerobic arachidonate-dependent hydroperoxidase activities. HS368 does have significant reducing agent-dependent hydroperoxidase activity suggesting that His-368 may not be an iron ligand but rather may be involved in interactions with arachidonic acid or the formation of the arachidonyl radical intermediate. HS373 contains no iron and has no detectable activities. PMID- 1510661 TI - Construction of a tRNA-embedded-ribozyme trimming plasmid. AB - We have combined Cotten and Birnstiel's tRNA-embedded ribozymes and our 5'- and 3'-trimming system. Although the activity of the tRNA-embedded ribozyme was ca. 30% lower than those of naked ribozymes, since the stability of the former in bovine serum was higher than those of naked ribozymes, the tRNA-embedded ribozymes appear useful especially when the 5'- and 3'-trimming units are concatenated in tandem. PMID- 1510662 TI - Effects of a bone lysine-rich 18 kDa protein on osteoblast-like MC3T3-E1 cells. AB - A lysine-rich 18 kDa protein was isolated from bovine bone and examined for its effects on osteoblast-like MC3T3-E1 cells. This protein is homologous to a heparin-binding protein in brain and uterus. This protein enhanced cell attachment independent of the Arg-Gly-Asp cell-binding sequence and stimulated proliferation during the growth phase. Addition of this protein to cell cultures on days 11, 12, and 13 after confluency resulted in a 1.6-2.0-fold increase in the alkaline phosphatase activity and little increase in the DNA content. These findings suggest that the 18 kDa protein may be functional in promoting the proliferation and differentiation of osteoblasts. PMID- 1510663 TI - Effect of glycolipids on the phase behavior and dynamic properties of phospholipid liposomes. AB - The glycolipids of Acholeplasma laidlawii AIH089 membranes were identified and purified. The effect of monoglucosyldiacylglycerol (MGDG) and diglucosyldiacylglycerol (DGDG) on the thermotropic behavior of multilamellar vesicles of dipalmitoylphosphatidylcholine (DPPC), dipalmitoylphosphatidylglycerol (DPPG) has been investigated by high sensitivity differential scanning calorimetry. The main transition peaks were broadened, the enthalpies were decreased. DGDG caused the decrease in the transition temperatures of DPPC, DPPG liposomes by 3.08 degrees C, 4.18 degrees C, respectively. MGDG did not cause the alteration of the transition temperature of DPPC liposomes but caused the decrease of the transition temperatures of DPPG liposomes by 2.20 degrees C. ESR experiments indicate that MGDG decreased the rotational correlation time of DPPC and DPPG liposomes. PMID- 1510664 TI - 4-Amino-6-methylhept-2-enoic acid: a leucine analogue and potential probe for localizing sites of proteolytic control in the hepatocyte. AB - A recent analysis of leucine analogues has suggested that the carboxyl group is not required for mediating low concentration proteolytic inhibition in liver cells. In designing a probe to localize the regulatory site(s), we tested this hypothesis by synthesizing an analogue with a 2-carbon insert between the carboxyl and alpha-carbon. The Wittig product, a trans olefin, was fully active. Surprisingly, low concentration activity was lost when the double bond was eliminated by hydrogenation although some inhibitory effectiveness at high concentrations was evident. Since the double bond extends the carboxyl group away from the alpha-carbon, the results support the above hypothesis as well as the feasibility of adding functional groups to the carboxyl end of leucine. PMID- 1510665 TI - Temperature-dependent protein folding in vivo--lower growth temperature increases yield of two genetic variants of Xenopus laevis Cu,Zn superoxide dismutase in Escherichia coli. AB - Two genetic variants of Xenopus laevis Cu,Zn superoxide dismutase, XSODA and XSODB, have been expressed in Escherichia coli by recombinant DNA techniques. Production of both proteins was obtained, although with different yields, XSODB being more abundant than XSODA in all the conditions tested. Lowering the temperature of growth was found to be a specific factor, decisive in obtaining quantitatively abundant, active Xenopus enzymes. Impaired folding of these proteins in the E.coli cytoplasm was found to parallel their in vitro properties. PMID- 1510666 TI - Nuclear proteins from Capan-2 cell line form specific complexes with the 17-1A antigen gene promoter. AB - To determine the location of sites important for the function of the 17-1A antigen gene promoter and to characterize the protein factors binding to these sites, fragments of the promoter region were analysed by gel retardation assay with nuclear extracts from Capan 2 cell line. At least two separate regions, which specifically bind nuclear proteins, were identified within the 5'flanking region of the 17-1A antigen gene. These regions have been located between nucleotides -877 to -518 (distal region) and -193 to +3 (proximal region) and presumably participate in regulation of expression of the 17-1A antigen gene. PMID- 1510667 TI - Heterotopic bone formation induced by bone morphogenetic protein in mice with collagen-induced arthritis. AB - A study was conducted to investigate the influence of systemic inflammation on heterotopic bone formation induced by bone morphogenetic protein (BMP). Five milligram pellets of BMP were implanted in mice with type II collagen-induced arthritis. Intraperitoneal injections of interleukin-1 (IL-1) were also administered to a group of mice without collagen-induced arthritis. The amount of BMP-induced heterotopic bone formation was evaluated by soft X-ray radiography, histology, and assay of calcium content. BMP-induced heterotopic bone formation was markedly enhanced in mice with collagen-induced arthritis, and also in IL-1 treated mice. These findings suggest that bone formation is enhanced in mice with collagen-induced arthritis, and that IL-1 may be responsible. PMID- 1510668 TI - Phospholipid import into mitochondria: possible regulation mediated through lipid polymorphism. AB - We previously demonstrated that the translocation of microsomal phosphatidylserine to the inner mitochondrial membrane occurs via contact sites before decarboxylation. According to the specific lipid composition of contact sites, we investigated lipid polymorphism as a possible regulation mechanism of phospholipid import into mitochondria. Phosphatidylserine import into mitochondria is increased in the presence of calcium, under conditions where non bilayer lipid-structures can be induced in cardiolipin-containing membranes. The results are discussed in terms of structural as well as functional domains heterogeneity within contact sites. PMID- 1510669 TI - Expression of the B cell-associated tyrosine kinase gene Lyn in primary neuroblastoma tumours and its modulation during the differentiation of neuroblastoma cell lines. AB - The src-related intracellular protein tyrosine kinase Lyn is a signal transducing molecule for surface immunoglobulin M and is expressed predominantly in hemopoietic cells. We report here the expression of the lyn gene in human neuroblastoma. In surgical tumour samples lyn transcripts were found preferentially at early stages whereas they were barely detectable in highly malignant tumours. In a cloned human neuroblastoma cell line, Be(2)C, lyn mRNA levels increased during neuronal differentiation induced by retinoic acid. Lyn mRNA levels were undetectable and did not respond to retinoic acid in a glial type neuroblastoma clone, SH-EP. Retinoic acid-induced glial differentiation was associated with a reduction of lyn transcripts in a clonal I-type neuroblastoma cell line, SH-IN, which shares properties of both neuronal- and glial-type clones. Like pp60c-src Lyn may be involved in a signalling pathway of neuroblasts committed to neuronal differentiation. PMID- 1510670 TI - Induction of platelet-derived growth factor chain A gene expression in human smooth muscle cells by oxidized low density lipoproteins. AB - Abnormal proliferation of vascular smooth muscle cells is a key event in the formation of atherosclerotic plaques in humans. It has been suggested that modulation of platelet derived growth factor chain A (PDGF-A) gene expression may contribute to atherosclerosis. Using an 'in situ hybridization' technique the present study shows that the presence of low density lipoproteins induces an eight fold increased expression of the transforming gene PDGF-A in human smooth muscle cells. The influence on PDGF-A expression only occurred after oxidative modification of low density lipoproteins, a process known to be important in atherogenesis. The non-atherogenic high density lipoproteins did not modulate the PDGF-A mRNA levels in smooth muscle cells. Consequently, oxidized low density lipoproteins may participate in atherosclerotic lesion formation as a result of autocrine stimulation of PDGF-A. PMID- 1510671 TI - Interaction of DNA with cationic liposomes: ability of transfecting lentil protoplasts. AB - The vesicle made of dipalmitoylphosphatidylcholine and stearylamine (9:1) were multilamellar and rather homogeneous in shape as seen by transmission electron microscopy. Upon addition of circular DNA plasmids of different lengths to the liposomes, the formation of vesicle clusters around the DNA filament was observed, with dimensions dictated by the ratio DNA/lipid. These liposomes were able to transfect lentil (Lens culinaris) protoplasts inside the cells two different reporter genes, chloramphenicol-acetyltransferase and beta glucuronidase. The activity of these two enzymes could be found in the cell lysates after 24 h from the incubation of protoplasts with the lipid-DNA complexes. PMID- 1510672 TI - Microbial oxidation of adamantanone by Pseudomonas putida carrying the camphor catabolic plasmid. AB - Intact cells of (+/-)camphor-grown Pseudomonas putida, ATCC17453(CAM), have been shown to oxidize readily the monoketone derivative of cage hydrocarbon adamantane, forming oxygenated products indicative of both biological Baeyer Villiger and hydroxylation reactions. Formed products were identified as 4 oxahomoadamantan-5-one, 5-hydroxyadamantan-2-one and 1-hydroxy-4-oxahomoadamantan 5-one. Minor products formed as a result of secondary reactions were tentatively identified as syn- and anti-1,4-dihydroxyadamantanes and bicyclo[3.3.1]nonan-3 ol. Adamantanone initial concentrations determined whether 1-hydroxy-4 oxahomoadamantan-5-one was the sole product (below 120 mg/l) or 4 oxahomoadamantan-5-one was the principle (up to 92%) product (240-600 mg/l). Formation of 1-hydroxy-4-oxahomoadamantan-5-one appears to occur by two routes determined by the sequence of lactonization and hydroxylation. PMID- 1510673 TI - Development of hydrophobicity parameters for prenylated proteins. AB - We have determined hydrophobicity parameters for the side-chains of the prenyl thioether protein modifications, farnesyl-cysteine and geranylgeranyl-cysteine. Farnesyl-Cys is somewhat more hydrophobic than palmitoyl-Cys, but geranylgeranyl Cys is more than two log(P) units more non-polar. These post-translational modifications represent the most hydrophobic residues yet described quantitatively. Furthermore, such modifications occur at the COOH-terminus which is generally methyl esterified. Loss of the terminal negative charge and formation of the ester proceeds with the gain of an additional 2.343 log(P) units of hydrophobicity. Clearly, COOH-terminal prenylation and esterification impart sufficient potential to render the terminus membrane bound. Thus, hydrophobicity parameters presented here for the prenylated amino acyl residues extend our understanding of these important physiological derivatives and enable computational analysis of proteins thus modified. PMID- 1510674 TI - Age-associated decreases in prostaglandin contents in human gastric mucosa. AB - This study was designed to clarify effects of ageing on human gastric mucosal prostaglandin (PG) contents. Forty examinees were divided into 5 age groups of 8 persons each, as follows: age under 40, age 40-49, age 50-59, age 60-69, and age over 70. PG contents in human gastric mucosa were measured by microcolumn high performance liquid chromatography (HPLC) with helium/cadmium laser induced fluorescence detection using biopsy samples obtained by endoscopy. The contents of 6-keto-PGF1 alpha, PGF2 alpha, PGE2, and PGD2 in the under 40 group were 638 +/- 39, 97 +/- 16, 468 +/- 68, 497 +/- 86 (pg/mg tissue), respectively. No significant differences in PG contents among groups aged under 70 were observed. In contrast, significantly low PG contents in the over 70 group were observed, i.e., the contents of 6-keto-PGF1 alpha, PGF2 alpha, PGE2, and PGD2 were 311 +/- 58, 36 +/- 8, 196 +/- 48, 171 +/- 40, respectively, and their contents were significantly lower than those in other age groups. In conclusion, gastric mucosal PG contents decrease significantly in over 70 years-old and this might be a contributing factor in the pathogenesis of gastric ulcers in elderly people. PMID- 1510675 TI - Genes for bone morphogenetic proteins are differentially transcribed in early amphibian embryos. AB - We have previously demonstrated that activin, a member of the TGF-beta family, has a potent mesoderm-inducing activity in Xenopus embryos. In the course of screening for activin-related genes from Xenopus, we have cloned cDNAs for Xenopus homologue of BMP-2, -4 and -7. Northern blot analysis revealed that these BMP genes are maternally encoded and differentially regulated after fertilization. Alkaline phosphatase-inducing assay using the recombinant BMP proteins has shown that at least BMP-2 and -4 have similar activity to mammalian counterparts. PMID- 1510676 TI - Sensitive detection and identification of mycoplasma-like organisms in plants by polymerase chain reactions. AB - DNA amplification by polymerase chain reactions (PCR) was employed to detect host plant infection by several mycoplasmalike organisms (MLOs), including the aster yellows (AY), dwarf aster yellows (DAY), and periwinkle little leaf (0-1) MLOs. For PCR, two pairs of oligonucleotide primers, designated AY18pm and AY19pm, respectively, were synthesized on the basis of partial sequences of cloned AY MLO DNA fragments AY18 and AY19. Reaction mixtures containing primer pair AY18pm yielded a DNA product of 1.6Kbp, when template consisted of DNA extracted from AY MLO- or DAY MLO-infected Catharanthus roseus (periwinkle). A DNA product of 1.0Kbp was obtained with primer pair AY19pm, when template consisted of DNA extracted from C. roseus infected by AY MLO, DAY MLO, or periwinkle little leaf (strain O-1) MLO. MLO-specific bands were observed when reaction mixtures contained as little as 5 pg total nucleic acid from infected plants. No PCR product was observed when reaction mixtures contained only DNA from healthy plants or DNA from plants infected by western X MLO or by tomato big bud MLO. The findings indicated that the PCR system is useful for sensitive detection and differentiation of MLOs in infected hosts. PMID- 1510677 TI - PDGF AA homodimers are potent chemoattractants for fibroblasts and neutrophils, and for monocytes activated by lymphocytes or cytokines. AB - The A-chain homodimers of the platelet-derived growth factor (PDGF AA) are widely expressed in normal and transformed cells. The mitogenic properties of PDGF AA are well established; however, the chemotactic potential of PDGF AA remains controversial. We now show that PDGF AA is a strong chemoattractant for human monocytes, granulocytes, and fetal bovine ligament fibroblasts. However, highly purified (greater than 98%) monocytes require the addition of lymphocytes or IL-1 for chemotactic responsiveness to PDGF AA but not for full chemotactic activity with formyl-methionyl-leucyl-phenylalanine (fMLP) or C5a. These results indicate that PDGF AA is a potent chemoattractant. These results also indicate that monocytes require activation either by lymphocytes or exogenous cytokines in order to respond chemotactically to PDGF AA but not to fMLP or C5a and suggest roles of the lymphocyte and cytokine in the chemotactic response of the monocyte to PDGF AA in vivo. PMID- 1510678 TI - Methylation inhibits the interaction of DNA binding proteins with a potential c abl intron regulatory element. AB - We have identified DNA binding proteins which interact with a sequence found in an intron of the tyrosine kinase coding portion of the murine c-abl gene. Several specific DNA: protein complexes were observed. Those complexes of approximate molecular weights 64 and 66kDa were detected when an Msp I site (CCGG) within the sequence was unmethylated, but were not observed when that site was methylated. Insertion of the intron sequence 5' to the rat somatic cytochrome C promoter and chloramphenicol acetyl transferase (CAT) sequences resulted in at least four-fold stimulation of CAT activity. These data suggest a potential role for the intron sequence in the regulation of gene expression. PMID- 1510679 TI - Isolation and structural characterization of a new crosslinking amino acid, cyclopentenosine, from the acid hydrolysate of elastin. AB - A novel polyfunctional crosslinking amino acid, which was developed slower than lysinonorleucine and faster than desmosine on thin layer chromatography, was isolated from the hydrolysate of bovine aorta elastin. Its proposed structure was verified by ultraviolet spectroscopy, fast atom bombardment mass spectroscopy, and nuclear magnetic resonance spectroscopy. The data indicated it to be a trifunctional amino acid with a cyclopentene structure. The mass spectral analysis indicated a parent compound with a mass of 381 (C18H27N3O6). The proposed structure is one derived from the condensation of three allysine residues. Based on the names of other crosslinking amino acids found in elastin, the trivial name of cyclopentenosine is given to this compound. PMID- 1510680 TI - SK&F 96365 inhibits histamine-induced formation of endothelium-derived relaxing factor in human endothelial cells. AB - Formation of endothelium-derived relaxing factor (EDRF) strictly correlates with the intracellular free Ca2+ ([Ca2+]i) concentration. We now demonstrate that the histamine-induced rise in [Ca2+]i of human umbilical vein endothelial cells is mostly due to activation of a membrane current which allows Ca2+ entry. This membrane current is sensitive to the novel inhibitor of agonist-induced Ca2+ entry, SK&F 96365, which blocked the histamine-induced sustained rise in [Ca2+]i, as well as 45Ca2+ uptake and membrane currents. Inhibition of the above cellular responses to histamine was accompanied by a considerable reduction of EDRF formation and release. Thus biosynthesis and release of EDRF from human umbilical vein endothelial cells significantly depend on agonist-induced Ca2+ entry involving receptor-operated Ca(2+)-permeable channels which can be blocked by SK&F 96365. PMID- 1510681 TI - Synthesis and purification of biologically active rat brain-derived neurotrophic factor from Escherichia coli. AB - The cDNA for rat brain-derived neurotrophic factor was cloned as the prepro and mature sequences into two independent expression vectors under control of the T7 promoter. When these vectors were transfected into Escherichia coli the prepro and mature forms of brain-derived neurotrophic factor accounted for about 20% and 25% of total E. coli proteins, and displayed molecular sizes of 26 kDa and 15 kDa, respectively. Mature brain-derived neurotrophic factor was extracted from E. coli inclusion bodies, refolded in the presence of CuCl2 and purified. The resulting protein had an ED50 of 3 ng/ml in supporting survival of cultured embryonic dorsal root ganglion neurons. PMID- 1510682 TI - The binding of bridged bis-pyridinium oximes to DNA and its relevance to the induction of mitochondrial dysfunction in yeast. AB - Bis-pyridium oximes and methoximes from a newly synthesized series are weak DNA binders (K = 3.10(4) M-1 under physiological conditions). From the number of binding sites per phosphate, 0.25, the ionic strength dependence of the binding constant and the negative electric dichroism, it is concluded that monointercalation is the mode of association. In contrast to methoxy compounds, the oxime derivatives are able both to induce the mutated "petite" phenotype in yeast S. cerevisiae and to cause "in vitro" extensive condensation of single stranded DNA. This reaction is postulated to be relevant to the mutational process that leads to "peptide" cells. The absence of nuclear mutation is interpreted in terms of sequestration of the drug in mitochondria under the effect of the organelle inner membrane electrochemical potential. PMID- 1510683 TI - Regulation of endothelin-1 synthesis in cultured guinea pig airway epithelial cells by various cytokines. AB - To study regulatory mechanisms influencing the synthesis and release of ET-1, a potent bronchoconstrictor, epithelial cells from guinea pig tracheas were cultured to test various cytokines for the synthesis of ET-1 and its precursor, big ET-1. Cytokines tested were divided into 4 groups, based on their potential modes of action. IL-8, TNF alpha and TGF beta transiently increased the synthesis of ET-1, while EGF, PDGF and GM/CSF promoted proliferation of ET-1 synthesizing cells. IL-1 enhanced the synthesis of ET-1 precursor without mitogenesis, whereas IL-2, IL-6 and IGF-1 induced both the synthesis of big ET-1 and mitogenesis. These observations suggest that cytokines involved in damage, inflammation and repair of the airway epithelial layer regulate the synthesis and release of ET-1 by multiple mechanisms, thereby influencing airway muscle tone. PMID- 1510684 TI - Molecular cloning and chromosomal mapping of a human protein-tyrosine phosphatase LC-PTP. AB - We isolated cDNA clones encoding a protein-tyrosine phosphatase (PTP) from a human T cell PEER cDNA library. The predicted open reading frame encodes a approximately 40-kDa protein composed of 360 amino acids and has no apparent hydrophobic segments, suggesting that it is a nontransmembrane PTP, which was designated as LC-PTP (leukocyte PTP). Northern blot analysis revealed that the LC PTP mRNA was preferentially expressed in a variety of hematopoietic cells and the transcriptional sizes were approximately 4.0 kilobases and approximately 2.9 kilobases. Fluorescent in situ hybridization revealed that the human LC-PTP gene is located on the chromosome region 1q32.1, which is known to be a site associated with chromosomal deletion in malignant lymphomas, where candidate tumor suppressor genes might be present. PMID- 1510685 TI - Peptide tyrosine phenylalanine: a novel neuropeptide F-related nonapeptide from the brain of the squid, Loligo vulgaris. AB - A novel nonapeptide, sequence YAIVARPRFamide, was isolated from brain extracts of the squid, L. vulgaris. Designated peptide tyrosine phenylalanine (PYF), the peptide shows marked homology with the C-terminal nonapeptides of pancreatic polypeptide and neuropeptide F (NPF) from a number of sources. If PYF is the C terminal nonapeptide of squid NPF, then it may be derived by a novel processing mechanism involving specific cleavage between two TYR residues. PYF may be a highly truncated, receptor-active variant of NPF. PMID- 1510686 TI - Evidence for thiophene-S-oxide as a primary reactive metabolite of thiophene in vivo: formation of a dihydrothiophene sulfoxide mercapturic acid. AB - Urine of rats treated with thiophene contains a very major metabolite which represents about 30% of the administered dose. A detailed analysis of its 1H and 13C NMR spectra and a study of its IR and mass spectra clearly showed that it was a 2,5-dihydrothiophene sulfoxide bearing a N-acetyl-cysteinyl group on position 2. Upon heating, it lost water with formation of N-acetyl-S-(2-thienyl)-L cysteine. A likely mechanism for the formation of this metabolite should involve the S-oxidation of thiophene as a primary step and the addition of glutathione to the very reactive thiophene-S-oxide. These data provide a first evidence for the intermediate formation in vivo of thiophene-S-oxides as reactive metabolites. PMID- 1510687 TI - Immunosuppressive molecules produced by Sertoli cells cultured in vitro: biological effects on lymphocytes. AB - In the present study we have analyzed the proteins secreted in vitro by murine Sertoli cells to identify immunosuppressive factors. Our data show that Sertoli cells secrete molecules capable to inhibit proliferation of lymphocytes activated in vitro. Cytophluorimetric analysis indicates that treated cells are arrested in the G1 phase of cell cycle. The inhibitory activity is specific for both B or T lymphocytes but not for other non-lymphoid cells and is associated to proteins, heat and freeze stable, with Mr of more than 30 kDa. Lymphocytes treated with Sertoli immunosuppressive proteins drastically reduce the secretion of interleukin-2. PMID- 1510688 TI - Cholesterylene, a newly recognized tissue lipid, found at high levels in the cornea. AB - In the course of measuring the concentration of cholesterol in an opacified dog cornea by gas-chromatography, relatively large amounts of an unidentified non saponifiable lipid were recognized. When the unknown lipid was subjected to gas chromatographic-mass spectral analysis it displayed a major ion at m/z 368 M+. and was identified as cholesta-3,5-diene, cholesterylene, by computer match with mass spectral-registry data. Cholesterylene was then shown to be present in the corneas of normal dogs, cows and humans, accounting for 20-25% of the total steroid-sterol in dog corneas and 5-10% in cow and human. Cholesterylene, which can be considered as an extremely nonpolar dehydration product of cholesterol, has not previously been recognized in animal tissues. Although the source of corneal cholesterylene is unknown, preliminary results suggest non-enzymatic formation from cholesterol. PMID- 1510689 TI - Interaction of ubiquinone and vitamin K3 with mitochondrial succinate-ubiquinone oxidoreductase. AB - Two new methods have been devised for measuring fumarate reduction by beef heart succinate-ubiquinone oxidoreductase with quinols as electron donors. In one assay the quinone is maintained in the reduced state by coupling fumarate reduction with the DT-diaphorase reaction, in the other assay by the presence of excess dithionite. The advantages of these methods are discussed, along with preliminary characterization of the quinol-protein interaction. PMID- 1510690 TI - Dichotomy in the laminin-binding properties of soluble and membrane-bound human galactoside-binding protein. AB - Recent studies indicate that galactoside-binding proteins may bind the poly-N acetyllactosamine sequences of laminin. We questioned whether human galactoside binding protein (hL-31) binds to laminin and whether cells that express hL-31 on their surface use it as a laminin receptor to promote cellular attachment. The data show that both lectin and cells bind to immobilized laminin. The binding of soluble lectin to laminin is inhibited by lactose, while cell adhesion to it is not. The results indicate that laminin may be a ligand for soluble galactoside binding proteins. PMID- 1510691 TI - Polyamines in neurotrauma. Ubiquitous molecules in search of a function. AB - In spite of their abundance, the function of PAs in the adult nervous system remains enigmatic. It is postulated that after trauma, the induction of polyamine metabolism (i.e. the polyamine response), which is inherently transient, is an integral part of a protective biochemical program that is essential for neuronal survival. Several functions ascribed to PAs may assume importance in cellular defense. Thus, regulation of the ionic environment, modulation of signal pathways, control of cellular Ca2+ homeostasis, inhibition of lipid peroxidation, and interaction with nucleic acids are all putative sites for PA action. During maturation, the CNS, unlike the peripheral nervous system, undergoes changes which result in the expression of an incomplete polyamine response after trauma. This may be due to an altered pattern of gene expression, and/or restrictive compartmentalization of the PAs and their metabolizing enzymes. Induction of this partial polyamine response after injury results in a sustained accumulation of putrescine, which by itself may be harmful, without the concomitant increase in spermidine and spermine. Administration of exogenous PAs after trauma exerts a neuroprotective effect. Exogenous PAs are postulated to gain access into cells via an induced uptake system after trauma, and function similarly to newly synthesized PAs. Besides the injured neurons themselves, tissues which are connected or associated with these neurons may be potential targets where PAs could act to stimulate neurotrophic factor production. Based on the neuroprotective effects of PAs in laboratory animals and on their proposed role in mechanisms of neuronal survival, the development of PA-based compounds as therapeutic neuroprotective agents should be pursued. PMID- 1510692 TI - The sensitivity of human tumour cells to quinone bioreductive drugs: what role for DT-diaphorase? AB - 15 human tumour cell lines (lung, breast and colon) have been evaluated for their sensitivity to the quinone based anti-cancer drugs Mitomycin C, Porfiromycin, and EO9 (3-hydroxymethyl-5-aziridinyl-1-methyl-2-(IH-indole-4,7-dione)prop-beta- en alpha-ol). Sensitivity has been compared with the intra-cellular levels of DT diaphorase, an enzyme thought to be important in the reductive activation of these quinones. No correlation exists between levels of DT-diaphorase and sensitivity to Mitomycin C or Porfiromycin. However, for EO9 those cell lines showing highest levels of DT-diaphorase activity tend to be the most sensitive. PMID- 1510693 TI - Demonstration of ryanodine-induced metabolic effects in rat liver. AB - The effects of ryanodine, a plant alkaloid which alters Ca2+ sequestration in the liver, on O2 uptake and gluconeogenesis were measured. Ryanodine administration to perfused rat liver resulted in the stimulation of O2 uptake and of gluconeogenesis. Because ryanodine does not affect directly mitochondrial respiration, its stimulatory effect on O2 uptake in the whole cell is likely to be secondary to the increased cytosolic free Ca2+ levels. PMID- 1510694 TI - Polarized efflux of 2',7'-bis(2-carboxyethyl)-5(6)-carboxyfluorescein from cultured epithelial cell monolayers. AB - We have investigated the polarity of the efflux of the intracellular pH fluorochrome 2',7'-bis(2-carboxyethyl)-5(6)-carboxyfluorescein (BCECF) from layers of epithelial Madin-Darby canine kidney (MDCK, Strains I and II) and human intestinal (Caco-2, HCT-8 and T84) cells grown on porous membranes. In Strain I MDCK cells, BCECF efflux was effectively reduced by indomethacin (50% inhibition with 100 microM) and 5-nitro-2-(3-phenylpropyl-amino)-benzoate (NPPB; 50% inhibition with 10 microM). Replacement of external Cl- with bromide, iodide or nitrate did not alter BCECF efflux, while substitution with methanesulphonate resulted in a small but significant reduction. All five cell lines form confluent epithelial layers when grown on porous membranes. Efflux of BCECF from Strain I MDCK epithelial layers into the apical solution was approximately three times greater than into the basal solution. Addition of indomethacin to the apical solution attenuated efflux into the apical but not the basal solution, while basal indomethacin was effective against basal efflux. NPPB has a similar specificity of action. Adrenaline, a stimulant of electrogenic Cl- secretion, did not alter the pattern of BCECF efflux. BCECF efflux was also polarized, with apical efflux greater than basal efflux, in MDCK Strain II and Caco-2 epithelial layers. In contrast, BCECF efflux into the basal and apical media was equivalent in layers formed from HCT-8 and T84 cells. However, indomethacin reduced efflux in all five epithelial lines, although the relative sensitivities of the apical and basal efflux rates to indomethacin varied, as did the sensitivity to the sidedness of application of indomethacin. In MDCK and HCT-8 epithelial layers, transepithelial vinblastine secretion mediated by P-glycoprotein was not inhibited by indomethacin. The data are consistent with the hypothesis that BCECF efflux is a manifestation of a novel ATP-dependent xenobiotic secretory efflux mechanism in renal and gastrointestinal epithelia. The factors regulating the polarity of BCECF efflux, both the indomethacin-sensitive and -insensitive components, have yet to be elucidated. PMID- 1510695 TI - Effects of cysteine and acetaminophen on the syntheses of glutathione and adenosine 3'-phosphate 5'-phosphosulfate in isolated rat hepatocytes. AB - The aim of the present study was to introduce and validate a radioactive tracer method in which adenosine 3'-phosphate 5'-phosphosulfate (PAPS) and glutathione (GSH) are measured simultaneously in isolated hepatocytes. PAPS and GSH are co substrates in sulphation and GSH conjugation, and both are dependent on sulphur deriving from cysteine. The effect of cysteine on the syntheses was investigated at non-toxic and toxic concentrations of the hepatotoxic drug acetaminophen (AA). Administration of AA trapped radioactivity (35S) in the pre-labelled PAPS and GSH pools by formation of the metabolites, AA-sulphate and AA-GSH. Turnover rates were determined from the decline of AA-sulphate and AA-GSH specific activity. Syntheses of PAPS and GSH were calculated by multiplying the rates with the concentrations of the respective co-substrates. Increasing AA concentration from non-toxic to toxic levels resulted in increased median PAPS and GSH syntheses (8 to 11 and 311 to 2218 nmol/10(6) cells/min, respectively) (P less than 0.05). Addition of cysteine did not alter median PAPS synthesis (5 to 3 nmol/10(6) cells/min) but decreased median GSH synthesis (666 to 261 nmol/10(6) cells/min) (P less than 0.05) in experiments with non-toxic AA concentrations. In experiments with toxic AA concentrations opposite effects of cysteine were seen, i.e. median PAPS synthesis was reduced (3 to 2 nmol/10(6) cells/min) (P less than 0.05) while median GSH synthesis was unchanged (23 to 16 nmol/10(6) cells/min). The present method provides a tool in which two important detoxification pathways can be measured simultaneously and the data suggest that the two pathways are regulated by substrate availability. PMID- 1510696 TI - Induction of cytochrome P450 activities by polychlorinated biphenyls in isolated mouse hepatocytes. Influence of Ah-phenotype and iron. AB - Exposure of cultured primary hepatocytes from Ah-responsive male C57BL/10ScSn mice to a polychlorinated biphenyl (PCB) mixture (Aroclor 1254) at 0.1-20 micrograms/mL for up to 96 hr induced cytochrome P4501AI-mediated activity (ethoxyresorufin O-deethylase, EROD) up to 50-fold. In contrast, pentoxyresorufin O-dealkylase (PROD), which in some circumstances is a measure of phenobarbitone induced cytochrome P450 isoenzymes, was induced only 5-fold. There were similar findings on EROD activities with the pure compounds 3,3',4,4',5,5' hexachlorobiphenyl, 3,3',4,4',5,5'-hexabromobiphenyl and 3,3',4,4' tetrachlorobiphenyl(TCB) and also beta-naphthoflavone but not with 2,2',4,4'-TCB or phenobarbitone. The higher concentrations of Aroclor 1254 were also associated with cytotoxicity as estimated by release of alanine aminotransferase (ALT) into the medium. Unlike in C57BL/10ScSn hepatocytes induction of EROD and cytotoxicity was minimal in hepatocytes from the Ah-non-responsive strain DBA/2. Although in vivo the hepatic toxicity and carcinogenicity of polyhalogenated aromatics are markedly potentiated by iron, no enhancement of the cytotoxicity of Aroclor 1254 towards C57BL/10ScSn hepatocytes by iron was observed in vitro. However, iron caused decreased EROD activities and possibly cytochrome P4501AI (as judged by Western blotting) as in vivo. Even in the presence of iron and the haem precursor 5-aminolaevulinic acid (5-ALA) there was no development of uroporphyria in this system although this occurs with Aroclor in vivo and is enhanced by iron. Accumulation of uroporphyrin did occur after extended culture of C57BL/10ScSn hepatocytes on matrigel for 8 days in the presence of 5-ALA and Aroclor 1254 but again no potentiation by iron was observed. Thus, although culture of Ah responsive and -non-responsive hepatocytes mimics some aspects of the mechanisms of in vivo toxicity of PCBs, there is some unknown associated influence of iron metabolism which cannot, as yet, be produced in vitro but which is of importance in vivo. PMID- 1510697 TI - Increased activity of the GABAergic system in selected brain areas after chronic propranolol treatment in spontaneously hypertensive rats. AB - The influence of chronically administered propranolol on the functional state of the gamma-aminobutyric acid-ergic (GABAergic) system in spontaneously hypertensive rats was studied and compared with the effect of dihydralazine. GABA content, synthesis and turnover rate in selected brain areas were assessed. Hypotensive activity of propranolol and dihydralazine after injection of GABA antagonist pictrotoxin was examined in acute experiment. Prolonged administration of propranolol increased GABA content, synthesis and turnover rate in the hypothalamus and the pons-medulla. After chronic injections of dihydralazine there was no change in GABA indices. Antihypertensive activity of dihydralazine in picrotoxin-treated animals remained unchanged. On the contrary, picrotoxin suppressed the propranolol-induced decrease in blood pressure. Our results indicate that propranolol increases GABAergic system activity. Therefore, we conclude that down-regulation of the GABAergic system in hypertension may be compensated by the regulatory action of propranolol. PMID- 1510698 TI - Kininase activity in human platelets: cleavage of the Arg1-Pro2 bond of bradykinin by aminopeptidase P. AB - A proline-specific peptidase aminopeptidase P (APP, EC 3.4.11.9) that cleaves the Arg1-Pro2 bond of bradykinin was isolated from human platelets by liquid chromatography. The enzyme was purified 557 times. The native molecule has a M(r) of 223,000. Human platelet APP exists as a trimer with a subunit M(r) of 71,000. The apparent Km of platelet APP is 66 mumol/L for bradykinin and 47 mumol/L for the internally quenched fluorogenic substrate Lys (2,4-dinitrophenyl)-Pro-Pro-NH CH2-CH2-NH-2-aminobenzoyl. 2HCl which is used for the routine determination of the enzyme activity. The optimum pH for hydrolysis of the fluorogenic substrate is 8.0, and the optimum temperature is 43 degrees. Platelet APP is inhibited by 1,10-phenanthroline and activated by Mn2+, thus confirming its metalloprotease nature. Cu2+, Zn2+ and Hg2+ are strongly inhibitory. Inhibition by cysteine protease inhibitors suggests the presence of a thiol group essential for enzymatic activity. Serine protease inhibitors do not affect the enzyme activity. PMID- 1510699 TI - Reduction of alpha-tocopherolquinone to alpha-tocopherolhydroquinone in rat hepatocytes. AB - The contents of alpha-tocopherolhydroquinone (TQH2), alpha-tocopherolquinone (TQ) and alpha-tocopherol (Toc) in isolated rat hepatocytes and liver homogenates were determined by HPLC under anaerobic conditions, because TQH2 easily autoxidizes to TQ under aerobic conditions. The viable hepatocytes were used for the determination without homogenization. The hepatocytes contained 3.1, ND and 5.0, 3.1-9.0, and 31.3-63.2 nmol of TQH2, TQ and Toc/g liver, respectively. However, TQH2 was not detected in liver homogenates because endogeneous TQH2 autoxidizes to TQ during preparation of homogenates under aerobic conditions. The homogenates contained 2.0-23.5 and 36.5-54.9 nmol of TQ and Toc/g liver, respectively. Addition of TQ showed that TQ was reduced and converted into TQH2 in isolated hepatocytes. The TQH2 formation from TQ was also observed in liver homogenates in the presence of either NADPH or NADH. The formation was further analysed and confirmed by HPLC and mass spectrometry. The formation of TQH2 was also found to occur in mitochondria, microsomes and cytosol. The specific activity of NADPH dependent TQ reductase activity was in the order of mitochondria greater than or equal to microsomes greater than cytosol. Furthermore, NADPH-cytochrome P450 reductase was found to catalyse TQH2 formation from TQ. PMID- 1510700 TI - Peroxide-dependent amino acid oxidation and chemiluminescence catalysed by magnesium-pyridoxal phosphate-glutamate complex. AB - Magnesium-pyridoxal-5'-phosphate-glutamate (MPPG) has been shown to ameliorate atherosclerotic symptoms in rabbits. In vitro, MPPG in the presence of peroxides such as cholesterolhydroperoxide or cumene hydroperoxide and Mn2+ ions produces "excited states" measurable as chemiluminescence or ethylene release from 1 aminocyclopropane-1-carboxylic acid (ACC). The reactions are stimulated synergistically by unsaturated fatty acids. Pyridoxal phosphate exhibits similar properties, but can be differentiated from the activities of MPPG or the sum of the components present in MPPG. PMID- 1510701 TI - Importance of hepatic metabolism in the antiaggregating activity of the thienopyridine clopidogrel. AB - The thienopyridine clopidogrel is not active in vitro and must be administered i.v. or orally, suggesting that metabolism is necessary for activity. To verify whether the effect after i.v. administration was consecutive to recycling by hepatic bile secretion of clopidogrel or its metabolite(s) in the digestive tract, a catheter was implanted in the choledocus of rats, preventing bile and pancreatic secretions from being excreted into the digestive tractus. Two hours after clopidogrel administration (10 mg/kg, i.v.), blood was withdrawn and platelet-rich plasma aggregation was measured after the addition of 5 microM ADP. Clopidogrel treatment was equally efficient for sham-operated and catheterized animals (% inhibition of platelet aggregation: 76% and 59%, respectively) suggesting that the i.v. effect of clopidogrel was independent of re-absorption of biliary-excreted products and consequently that enteric metabolism is not necessary for activity. The antiaggregating activity of clopidogrel in rats before and after functional hepatectomy by a porto-jugular shunt was then studied. A great difference between treated animals was observed 30 min after i.v. administration of 25 mg/kg of clopidogrel. Per cent inhibition of platelet aggregation was 76% and 6% (P less than 0.001) for sham-operated and hepatectomized animals, respectively. Similar results were obtained after intraduodenal administration of clopidogrel, showing that the treatment was completely ineffective in hepatectomized animals. In isolated, blood-perfused rat livers, clopidogrel inhibited ADP-induced platelet aggregation, thereby supporting the theory that the activity of clopidogrel is highly dependent on hepatic metabolism. PMID- 1510702 TI - Effect of purification, theophylline and sodium fluoride on histamine release produced by antineoplastic drugs on rat mast cells. A distinctive mechanism of action for carboplatin. AB - The antineoplastic drugs, cytarabine, ifosfamide, vinorelbine, doxorubicin, asparaginase and carboplatin, elicit histamine release from rat pleural and peritoneal mast cells. Both cell populations do not show heterogeneity in their response to stimulation by any of these drugs, with the exception of cytarabine, which activates pleural mast cells at lower concentrations. When these cells are purified with Percoll, L-asparaginase, vinorelbine and cytarabine completely lose their capability of inducing histamine release in both cell populations, while the other drugs still show the same pattern of response as with unpurified cells. These results indicate that some membrane component crucial for the action of vinorelbine, L-asparaginase and cytarabine is lost during the purification procedure. Pretreatment of the cells with theophylline completely inhibits the response to cytarabine, ifosfamide, vinorelbine and asparaginase, and inhibits the response to doxorubicin by up to 75% only. Theophylline does not change the response to carboplatin. Sodium fluoride does not change the response to any of the drugs tested, with the exception of carboplatin, in which case a complete inhibition is observed. In conclusion, carboplatin activates rat mast cells through a completely different mechanism of action with respect to the other drugs studied. PMID- 1510704 TI - Studies of chlorambucil-DNA adducts. AB - Chlorambucil (CLB) is a bifunctional nitrogen mustard whose therapeutic and major side-effects are thought to be caused by binding to DNA. HPLC analysis of hydrolyzed DNA from L1210 cells incubated with [14C]CLB generated two peaks of radioactivity, indicating the formation of two or more major adducts. Since DNA incubated with [14C]CLB in a cell-free system gave rise to the same profile, experiments were conducted with DNA from cells exposed to radiolabeled DNA precursors, which was then reacted with CLB. DNA containing [8-14C]guanine gave rise to one peak of radioactivity, while DNA containing [2,8-3H]adenine gave rise to two peaks. These peaks corresponded to the peaks seen in the experiment with intact L1210 cells treated with [14C]CLB. Experiments with DNA containing [5 3H]cytosine indicated that no cytosyl adducts were formed. No adducts were seen in hydrolysates prepared from labeled DNA incubated with drug solvent alone. These data indicate that the majority of adducts induced by CLB are guanyl adducts, but a substantial quantity of adenyl adducts has also been identified. PMID- 1510703 TI - Differential stimulation of the GTPase activity of G-proteins by polylysine. AB - Polylysine, polyornithine and, to a lesser extent, polyarginine were found to stimulate the GTPase activity of the purified recombinant alpha subunit of the human G(i)-3 transducing protein alpha i-3. Optimal stimulation of 4- to 5-fold was obtained with polylysine concentrations between 1 and 20 microM, higher concentrations being inhibitory. Polylysine at similar concentrations stimulated by 50% the GTPase of transducin (GT), the vision transducing protein, but had only a very slight effect on the GTPase of the p21 product of the H-ras protooncogene. The stimulation of the alpha i-3 GTPase caused by polylysine was due to a reduction of the apparent Km for GTP from 3.8 to 1.3 microM. The stimulation by polylysine was observed at free Mg2+ concentrations below 1 microM. These results indicate that polylysine acts in a fashion similar to mastoparan and substance P in mimicking the action of an agonist-bound receptor on G-proteins. PMID- 1510705 TI - Primaquine metabolism by human liver microsomes: effect of other antimalarial drugs. AB - A number of drugs have been studied for their effect on the metabolism of the antimalarial drug primaquine by human liver microsomes (N = 4) in vitro. The only metabolite generated was identified as carboxyprimaquine by co-chromatography with the authentic standard. Ketoconazole, a known inhibitor of cytochrome P450 isozymes, caused marked inhibition of carboxyprimaquine formation with IC50 and K(i) values of 15 and 6.7 microM, respectively. This finding and the dependency of metabolite formation on NADPH indicates that cytochrome P450 isozyme(s) catalysed metabolite production. Of compounds actually or likely to be coadministered with primaquine to malaria patients, only mefloquine produced any inhibition (K(i) = 52.5 microM). Quinine, artemether, artesunate, halofantrine and chloroquine did not significantly inhibit metabolite formation. It seems unlikely that the concurrent administration of mefloquine, or other antimalarials, with primaquine will lead to appreciably altered disposition. PMID- 1510706 TI - Inhibitory potency of some isatin analogues on human monoamine oxidase A and B. AB - Isatin is an endogenous compound which acts as a selective inhibitor of monoamine oxidase (MAO) B. In this study a range of isatin analogues were tested for their in vitro inhibition of human MAO A and B. Most of the analogues were less potent than isatin. Hydroxylation of the aromatic ring changed the inhibitory potency in favour of MAO A, with 5-hydroxyisatin being a potent and selective MAO A inhibitor (IC50 8 microM). Isatinic acid, which is formed reversibly from isatin at alkaline pH, showed no inhibition. PMID- 1510707 TI - A novel note on the effect of ara-C on the polyamine content of the male accessory organs of the rat. AB - The effects of 1-beta-D-arabinosylcytosine (ara-C) given for 5 days on body weight, on the weights of the prostate, seminal vesicles and testis, and on the polyamine content (putrescine, put; spermidine, spd; spermine, spm) in these organs were examined in rats. The body weights of the ara-C-treated rats showed a decrease of 13% (P less than 0.01) and the weights of the prostate, seminal vesicles and testis were reduced by 20% (P less than 0.05), 13% and 5.0% (P less than 0.1), respectively. However, put, spd and spm contents in the ara-C-treated prostate were increased 1.2, 1.8 and 2.9 times, respectively. The contents of these polyamines in the ara-C-treated seminal vesicles increased about 40% for all polyamines. Both spd and spm in the treated testis showed a significant increase of about 20% (P less than 0.05) as compared with the control. In addition, the total polyamines in the whole organs increased significantly in both the prostate and testis. PMID- 1510708 TI - Induction of rat hepatic and intestinal glutathione S-transferases by dietary butylated hydroxyanisole. AB - To obtain insight into the protection mechanism of butylated hydroxyanisole (BHA), a widely used food preservative with anticarcinogenic properties, we investigated the effects of dietary BHA on rat hepatic and intestinal glutathione S-transferase (GST) enzyme activity, and GST isozyme levels. In the proximal small intestine and liver, BHA supplementation significantly increased GST enzyme activity as compared with controls (2.3- and 1.7-fold, respectively, P less than 0.05). GST class alpha and mu contents were significantly higher only in the small intestine (1.6-2.1-fold and 1.3-1.5-fold, respectively, P less than 0.05), whereas GST class pi was significantly induced in liver (4.6-fold, P less than 0.05). PMID- 1510709 TI - Splanchnic uptake of haloperidol and release of reduced haloperidol in vivo in the guinea pig. AB - Splanchnic uptake of haloperidol (HAL) and release of reduced haloperidol (RHAL) were studied in vivo in guinea pigs. Anesthetized animals with implanted cannulae in the aorta, the hepatic vein and the inferior vena cava were infused intravenously with HAL at a rate of 9.6 micrograms/min/animal for 90 min. Plasma HAL and RHAL in samples taken from the arterial and hepatic venous cannulae were measured by HPLC with an electrochemical detector. Contamination of the hepatic venous samples by blood from the inferior vena cava was ruled out by the validation method of tritiated water washout [Huang MT, J Appl Physiol 71: 359 364, 1991]. HAL concentrations plateaued at 70-80 ng/mL in the aorta and 5-7 ng/mL in the hepatic vein during the final 30 min of infusion. Splanchnic extraction of HAL was 91%. Hepatic blood flow was estimated to be 1.95 +/- 0.40 (SD) mL/min/g. If assuming that splanchnic uptake of HAL took place in the liver, a rate of uptake of HAL in the liver of 79.2 +/- 18.6 (SD) ng/min/g could be calculated by the Fick principle. The uptake in the whole liver accounted for 14% of the rate of HAL infusion into the animal. Plasma RHAL in the aorta, 6.4 +/- 6.6 (SD) ng/mL at 60 min and 9.4 +/- 4.6 (SD) ng/mL at the end of HAL infusion, was about 10-12-fold less than aortic HAL. The concentrations of RHAL in the hepatic vein were not significantly different from those in the aorta, indicating that splanchnic tissues including the liver are not responsible for plasma RHAL secretion. The highly efficient uptake of HAL as well as the ketone reductases found previously in vitro in liver microsomes of guinea pigs were probably involved only in biliary excretion of HAL. PMID- 1510710 TI - Catalytic activities of human debrisoquine 4-hydroxylase cytochrome P450 (CYP2D6) expressed in yeast. AB - A 1.57kb BamH1 fragment containing a full-length human debrisoquine 4-hydroxylase cytochrome P450 (CYP2D6) cDNA was inserted into the BglII site of the yeast expression plasmid pMA91 and the resulting recombinant plasmid, PELT1, introduced into Saccharomyces cerevisiae strain AH22. Microsomes prepared from AH22/pELT1 cells gave an absorption maximum at 448 nm and a P450 content of 67 +/- 31 pmol/mg of microsomal protein. No P450 was detectable in microsomes prepared from AH22/pMA91 control cells. A western blot of microsomes prepared from yeast transformed with pELT1 were probed with a monoclonal antibody to CYP2D6 and revealed a strong band with a molecular mass consistent with that of CYP2D6 from human liver microsomes. No corresponding band was observed with microsomes from control yeast transformed with pMA91 alone. Microsomes from AH22/pELT cells showed catalytic activity towards metoprolol (alpha-hydroxylation and O demethylation, 0.17 and 0.78 nmol/mg protein/h, respectively); and towards sparteine (2- and 5-dehydrogenation, 1.82 and 0.59 nmol/mg protein/h, respectively). The inhibition of metoprolol metabolism by quinidine (Qd) was 200 times more potent than that of quinine (Qn), both for alpha-hydroxylation (Qd IC50 = 0.05 microM; Qn IC50 = 4 microM) and O-demethylation (Qd IC50 = 0.05 microM; Qn IC50 = 4 microM). Negligible metabolism of tolbutamide and S mephenytoin, substrates of the 2C sub-family, and of p-nitrophenol, a substrate of CYP2E1, was detected, although a trace of the N-deethylated metabolite of lignocaine, thought to be metabolised by CYP3A4, was detected with microsomes from CYP2D6-expressing yeast cells. The results indicate that yeast cells containing human CYP2D6 cDNA express a functionally active form of the enzyme, the immunochemical and catalytic properties of which are consistent with those of human liver. PMID- 1510711 TI - The topography of trifluoroacetylated protein antigens in liver microsomal fractions from halothane treated rats. AB - Sera from patients with halothane hepatitis contain immunoglobulin G (IgG) antibodies to trifluoroacetylated liver microsomal proteins of 100, 76, 59, 57 and 54 kDa, which are produced as a consequence of metabolism of halothane to trifluoroacetyl halide by cytochrome(s) P450. In the present study, the membrane topographies of the various antigens in rat liver microsomal fractions were investigated. Liver microsomal fractions from rats treated with halothane in vivo, and rat liver microsomal fractions which had been incubated with halothane in vitro, were used as the source of trifluoroacetyl antigens. The antigens were detected by immunoblotting. Whereas the 100, 76, 59 and 57 kDa antigens were solubilized from the microsomal membrane by either 0.1 M sodium carbonate or 0.1% (w/v) sodium deoxycholate, the 54 kDa antigen was not solubilized by 0.1% (w/v) sodium deoxycholate. In intact microsomal fractions, the 100, 76, 59 and 57 kDa antigens were not degraded appreciably by trypsin unless detergent was added to permeabilize the microsomal membrane. These results indicate that the 54 kDa antigen is an integral membrane protein, whereas the 100, 76, 59 and 57 kDa antigens are peripheral membrane proteins situated within the lumen of microsomal vesicles, and hence presumably located within the lumen of the endoplasmic reticulum in vivo. PMID- 1510712 TI - Salicylate-induced cation fluxes across biological membranes. A study of the underlying mechanism. AB - The effect of salicylate on cation transport by lactating rat mammary tissue has been examined. Consistent with previous results, salicylate increased the unidirectional efflux of K+ (Rb+): this increase was dependent on extracellular Ca2+. Lowering the temperature of the incubation medium from 37 degrees to 4 degrees did not attenuate the effect of salicylate on K+ (Rb+). Ca2+ uptake by mammary tissue was stimulated by salicylate, whereas Ca2+ efflux was not greatly affected. Salicylate reduced the ouabain-insensitive uptake of K+ (Rb+). The net K+ content of mammary tissue was reduced by incubating tissue in a medium containing salicylate, whereas net Na+ content was increased. The results are consistent with the hypothesis that salicylate activated a calcium-dependent K+ efflux channel and/or a calcium-dependent non-selective cation channel. PMID- 1510713 TI - The microsomal demethylation of N,N-dimethylbenzamides. Substituent and kinetic deuterium isotope effects. AB - The metabolism of N,N-dimethylbenzamides by phenobarbital-induced rat liver microsomes results in the formation of N-methylbenzamides and formaldehyde. The reaction proceeds via the formation of an intermediate N-hydroxymethyl-N methylbenzamide, which, for the microsomal oxidation of N,N-dimethylbenzamide, was isolated and characterized. Confirmation of the N-hydroxymethyl-N methylbenzamide was obtained by its independent synthesis from N-methylbenzamide and formaldehyde. The intermolecular kinetic deuterium isotope effects for the reaction are 0.9 (+/- 0.1) for Vmax and 1.4 (+/- 0.1) for Vmax/Km. The intramolecular kinetic deuterium isotope effect, determined from the relative amounts of N-methylbenzamide and N-trideuteriomethylbenzamide formed in the microsomal demethylation of N-trideuteriomethyl-N-methylbenzamide, is 6.0 +/- 0.3. There is no correlation of Vmax or Vmax/Km with the substituent in the aromatic ring, nor with the calculated ionization potentials of the benzamides. The results are interpreted in terms of a mechanism in which the benzamide undergoes direct hydrogen atom abstraction to form a carbon centred radical. This carbon centred radical subsequently forms an N-hydroxymethyl-N-methylbenzamide that decomposes to formaldehyde and an N-methylbenzamide. Semi-empirical AM1 self consistent field molecular orbital calculations identify that loss of a hydrogen atom from the E-methyl group is thermodynamically more favourable than from the Z methyl group by ca. 5 kJ/mol. PMID- 1510714 TI - Cycloheximide treatment of mouse mast cells inhibits serotonin release. Evidence of a requirement for newly synthesized protein in the exocytotic response. AB - Treatment of mouse peritoneal mast cells and mouse bone marrow-derived cloned mast cells with the protein synthesis inhibitor cycloheximide led to a marked abrogation of serotonin (5-hydroxytryptamine; 5-HT) release induced by a range of activators including antigen, anti-immunoglobulin E (anti-IgE) antibody, calcium ionophore A23187, and the polycation polylysine. Significant inhibition (28%) of IgE-mediated secretion was attained after incubation of peritoneal cells for only 2 hr, and inhibition progressed over a 24 hr period, reaching greater than 80% after 15 hr. When peritoneal mast cells were exposed to cycloheximide and then washed and returned to culture conditions, a substantial recovery of responsiveness to anti-IgE was seen after 5 hr. Under the same conditions to those used in functional studies, cycloheximide inhibited protein synthesis, measured as incorporation of [35S]-methionine, by purified peritoneal mast cells and cloned mast cells to 18.5% and 7.9% of control levels, respectively. These results show that synthesis of new protein over a period of a few hours is required to render mast cells fully responsive to stimuli that act via the IgE receptor, and to certain other stimuli that are receptor-independent. PMID- 1510715 TI - Effects of oral hypoglycaemic agents on platelet functions. AB - The in vitro effects of three oral hypoglycaemic agents, gliclazide (1-(4 methylbenzensulfonyl)-3-[3-azabicylo(3,3,0)octyl]urea) , glibenclamide (1-[4-[2 (chloro-2-methoxybenzamide)-ethyl]-phenyl- sulfonyl]-3-cyclohexyl-urea) and glimepiride (1-[4-[2-(3-ethyl-4-methyl-2-oxo-3-pyrroline-carboxamide)- ethyl] phenylsulphonyl]3-(4-methylcyclohexyl)-urea), on functions of human platelets were evaluated. None of these agents up to a concentration of 40 microM inhibited platelet aggregation induced by thrombin. Glibenclamide and glimepiride in the range of 20-40 microM suppressed Ca2+ release from internal Ca2+ stores induced by thrombin. Gliclazide showed no effect on arachidonic acid metabolism of human platelets. Glimepiride selectively inhibited the cyclooxygenase pathway, while the activities of 12-lipoxygenase and phospholipase A2 were unaffected. Glibenclamide inhibited both the cyclooxygenase and 12-lipoxygenase pathways. It also attenuated arachidonic acid release from phospholipase A2. Oral hypoglycaemic agents with inhibitory effects on arachidonic acid metabolism may prove useful for the treatment of diabetic patients with enhanced platelet functions. PMID- 1510716 TI - Purification and characterization of 3-mercaptolactic acid S-conjugate oxidases. AB - Two enzymes catalysing the oxidative formation of 3-mercaptopyruvic acid S conjugates from L-3-mercaptolactic acid S-conjugates were purified to apparent homogeneity from rat liver cytosol. The two enzymes, tentatively designated MLO-I and MLO-II, showed a molecular mass of 160 and 250 kDa and were composed of four and six subunits of 41 and 39 kDa, respectively. Both enzymes possessed flavin mononucleotide as prosthetic group and oxidized several aromatic and aliphatic S substituted L-3-mercaptolactic acids as well as alpha-hydroxy acids such as L-3 phenyllactic acid and L-2-hydroxyisocaproic acid. Glycolic acid and 3-(4 hydroxyphenyl)-lactic acid were the specific substrates for MLO-I and MLO-II, respectively. Neither of the enzymes oxidized beta- and gamma-hydroxy acids such as 3- and 4-hydroxybutyric acid. 2-Hydroxyisobutyric acid, ethyl-2 hydroxybutyrate, malic acid, 1-butanol, benzyl alcohol and L-leucine did not act as substrates for the enzymes. MLO-I and MLO-II exerted their maximum activities around pH 5.5 with Km of 0.5 and 0.25 mM and Vmax of 0.9 and 0.2 mumol/min/mg, respectively, when S-(4-bromophenyl)-3-thiolactic acid was used as substrate. MLO I was inhibited by sulphydryl-modifying agents, while MLO-II was not. Both enzymes were strongly inhibited by divalent metal ions. These results indicate that MLO-I and MLO-II are different from L-amino acid oxidase (EC 1.4.3.2), malate oxidase (EC 1.1.3.3), L-alpha-hydroxy acid oxidase (EC 1.1.3.15) and glycolate oxidase (EC 1.1.3.1). The present enzymes are likely to be involved in the formation of cysteine conjugates from L-3-mercaptolactic acid S-conjugates in conjunction with cysteine conjugate aminotransferases. PMID- 1510717 TI - In human monocytes interleukin-1 stimulates a phospholipase C active on phosphatidylcholine and inactive on phosphatidylinositol. AB - Interleukin-1 (IL-1) can initiate the synthesis of prostaglandins which in turn act as endogenous modulators of IL-1 production. The human monocyte/macrophage synthesizes various eicosanoids through the activation of the cellular phospholipase system. Cell stimulation results in the activation of phospholipase A2 (PLA2) whose major substrate is phosphatidylcholine (PC) and the release of the eicosanoid precursor arachidonic acid (AA) from PC. Another pathway is the stimulation of a phospholipase C (PLC) mainly active on phosphoinositides and the resulting formation of inositol phosphates (IPs) and diacylglycerol (DAG). Phospholipids other than phosphoinositides can also be hydrolysed by PLC to give rise to DAG. Studies have shown that IL-1 does not activate the IP pathway, but it primarily stimulates a PLC linked to phosphatidylethanolamine in cultured rat mesangial cells, and a PLC linked to PC in Jurkart cells. We have stimulated human monocytes with IL-1 and calcium ionophore A23187 and we have observed their effect on the phospholipase system. The results indicate that IL-1 does not activate the formation of IPs in cells labeled with [3H]myo-inositol. In contrast, in cells labeled with [3H]AA, IL-1 causes the formation of DAG associated with the hydrolysis of PC. Moreover, after stimulation with IL-1 there is no accumulation of free AA which would indicate that there has been no activation of PLA2, which occurs instead with A23187 stimulation. These data suggest that, in monocytes, IL-1 does not directly stimulate a PLA2 or a PLC active on phosphatidylinositol; instead it primarily stimulates a PLC active on PC. PMID- 1510718 TI - Cadmium induction of renal and hepatic ornithine decarboxylase activity in the rat. Effects of sex hormones and involvement of the renin-angiotensin system. AB - We investigated the effect of sex hormones on the sex-dependent response of rat kidney ornithine decarboxylase (ODC) activity to cadmium (Cd) administration and the involvement of the renin-angiotensin system in mediating stimulation of the liver enzyme by the metal. The response of renal ODC to Cd, which occurs in intact adult males but not in females, is also detectable in prepubertal and castrated males. Upon treatment with 17 beta-estradiol, the basal levels of enzyme activity in intact or castrated adult males were enhanced and Cd administration failed to increase them further. In adult females the kidney enzyme became responsive after ovariectomy. Also, in prepubertal females renal ODC was induced by Cd, and this was prevented by treatment with 17 beta estradiol. Under the same conditions, changes in the levels of Cd accumulation within the kidney, that might account for variations in the response of ODC activity, did not occur. Cd caused an increase in renin activity starting minutes after its injection. Captopril, which specifically inhibits the conversion of angiotensin I to angiotensin II, prevented completely the induction of liver ODC by this metal; stimulation of the enzyme by Co was not affected by the drug. A similar inhibitory effect was exerted by propranolol. Adrenalectomy had no influence on the response of hepatic ODC to Cd; the decarboxylase was unaffected by aldosterone administration. It is suggested that Cd may induce liver ODC through the increase in angiotensin II following stimulation of renin by the metal. PMID- 1510719 TI - Effect of 2,2'-dicarbomethoxylamino-5,5'-dibenzimidazolyl ketone on antioxidant defenses of Acanthocheilonema viteae and its laboratory host Mastomys natalensis. AB - The effect of the macrofilaricidal agent of 2,2'-dicarbomethoxylamino-5,5' dibenzimidazolyl ketone (C.D.R.I. compound 82/437), on the metabolism of reactive oxygen species (ROs) in Acanthocheilonema viteae and Mastomys natalensis was measured following intraperitoneal administration at therapeutic doses. The recovered worms possessed substantially reduced levels of catalase and glutathione peroxidase (GPx), and thus were less able to detoxify H2O2. Nonetheless, the subcutaneous and adjoining muscle tissues, in which the parasites were lodged, exhibited elevated levels of antioxidant enzymes and reduced glutathione. It is concluded that compound 82/437 kills the filariid by paralysing its H2O2 detoxifying capacity without altering ROs metabolism in the tissue in which the parasite resides. Furthermore, since catalase and GPx of the liver and lungs do not show sign of inhibition, a difference appears to exist in the enzymes of the parasite and the host. PMID- 1510720 TI - Evidence for a bioactive clonidine-displacing substance in peripheral tissues and serum. AB - Clonidine-displacing substance (CDS) from brain is biologically active in the kidney and stomach and on platelets. To determine whether CDS is contained in these and other peripheral tissues, homogenates of fresh brain, eight other organs and serum from rat were ultrafiltered (less than 10,000 mol. wt only), dried and extracted with methanol. Evaluation by radioimmunoassay (RIA) using antibodies to p-aminoclonidine showed that adrenal gland and gastric fundus (GF) contained significantly greater amounts of CDS-like radioimmunoactivity than brain; intermediate-to-low activity was present in heart, small intestine, serum, kidney and liver; lung and skeletal muscle values were near-background. RIA positive extracts elicited well-correlated contractile activity in a GF smooth muscle bioassay; contractions persisted in the presence of antagonists of various transmitters and modulators, but were abolished by low concentrations of the calcium channel blocker verapamil. Serum levels of CDS were profoundly reduced following removal of the adrenal glands. We conclude that a CDS-like substance is present not only in brain as previously reported, but also in peripheral organs and in the circulation. PMID- 1510721 TI - 17 alpha-Z-[125I]iodovinyloestradiol and its 3-acetate: chemical synthesis in vivo distribution studies in the rat. Comparison of tissue accumulation and metabolic stability with 17 alpha-E-[125I]iodovinyl and 16 alpha-[125I]iodo oestradiols. AB - Certain oestrogens on substitution with halogens, have been shown to retain receptor binding affinity and accumulate in target tissues and therefore could, when labelled with gamma-emitting halogen isotope, act as radiopharmaceuticals for the imaging of receptor positive breast tumours. In order to evaluate putative radiopharmaceuticals, 17 alpha-Z-iodovinyloestradiol ((17 alpha,20Z)-21 iodo-19-norpregna-1,3,5(10),20-tetraene-3,17 beta-diol) and its 3-acetate have been chemically synthesized and labelled with 125I. Tissue distribution studies in female rats have been compared to those obtained using 17 alpha-E [125I]iodovinyloestradiol ((17 alpha,20E)-21-[125I]iodo-19-norpregna-1,3,5(10),20 tetraene-3,17 beta-diol) and its 3-acetate and to 16 alpha-[125I]iodo oestradiol (1,3,5(10)-estratien-16 alpha-[125I]iodo-3,17 beta-diol). All compounds showed a similar tissue distribution with the highest concentrations (cpm/g tissue) in the thyroid greater than liver greater than uterus greater than kidney greater than lung greater than blood greater than heart, spleen. The concentration in the uterus was highest after injection of 17 alpha-Z-iodovinyloestradiols or 16 alpha iodo oestradiol. Target (uterus) to background (blood) tissue ratios were highest after injection of 17 alpha-Z-iodovinyloestradiol-3-acetate and 16 alpha-iodo oestradiol (6:1). Deiodination in vivo took place to a small degree, amounting to 1.6%, 0.9% and 0.35% of the injected dose after 4 hr with the 17 alpha-Z, 17 alpha-E and 16 alpha compounds, respectively. For reasons of chemical expediency and consideration of the biological results 17 alpha-Z-iodovinyloestradiol-3 acetate is the compound of choice for the detection of oestrogen receptor positive tissues. PMID- 1510722 TI - Effects of cyclophosphamide and adriamycin on rat hepatic microsomal glucuronidation and lipid peroxidation. AB - The effect of cytotoxic drug administration, as a single dose i.p. to rats (six rats/treatment group), on hepatic microsomal UDP-glucuronosyltransferase (UGT) activity was investigated. Glucuronidation of morphine in microsomes from control rats apparently involved at least two enzymes. Administration of cyclophosphamide (CP; 200 mg/kg 7 days prior to killing) significantly increased the rate of morphine glucuronidation over the range 0.05-10 mM, and significantly increased the apparent Vmax for the high capacity isoenzyme from 1.25 +/- 0.12 to 1.95 +/- 0.39 nmol/mg/min. In contrast, the activity of 1-naphthol UGT was not significantly altered by administration of CP. Rats treated with the same dose of CP 1 day prior to killing showed a significant decrease in microsomal morphine UGT activity at 0.05 and 2.5 mM morphine, but a significant increase in activity was observed following administration of CP or Adriamycin (AD; 10 mg/kg) 4 days prior to killing. The extent of microsomal lipid peroxidation was significantly increased in microsomes obtained from rats treated with CP or AD 4 days prior to killing, and was positively correlated (P less than 0.001) with the rate of glucuronidation of 0.05 and 2.5 mM morphine. Preincubation of microsomes in the presence of CP (5 mM) and AD (100 microM) significantly decreased the rate of glucuronidation of 2.5 mM morphine. In vitro NADPH-mediated lipid peroxidation significantly increased the activity of both the high and low affinity morphine UGT isoenzymes. Administration of the cytotoxic drugs CP and AD may alter microsomal morphine-UGT activity via the process of lipid peroxidation, although other mechanisms cannot be excluded. PMID- 1510723 TI - Evaluation of adriamycin-induced lipid peroxidation. AB - Lipid peroxidation is known to be a mechanism for Adriamycin-induced toxicity. In the present study, two methods which detect fluorescent substances and high molecular weight protein aggregates in peroxidized membranes were applied to Adriamycin-induced lipid peroxidation in liver microsomes. A rat liver microsomal suspension containing an NADPH-generating system was incubated with Adriamycin. Thiobarbituric acid reactive substances (TBA-RS), formed during this incubation, were transferred from the microsomes to the medium. Fluorescent substances determined by the fluorescence emitted from both the microsomes themselves and the chloroform/methanol extracts of the microsomes, were found to be formed during this incubation. High molecular weight protein aggregates determined by sodium dodecyl sulfate-polyacrylamide gel electrophoresis, were also formed. Fluorescent substances and high molecular weight protein aggregates were found in microsomal membranes themselves and increased time dependently. These substances retained in membranes can be of great use to delineate the site of Adriamycin induced lipid peroxidation in vitro and in vivo and to determine how this lipid peroxidation affects the membrane. PMID- 1510724 TI - A deuterium NMR and steady-state fluorescence anisotropy study of the effects of cholesterol on the lipid membrane-disordering actions of ethanol. AB - We examined the effects of cholesterol on the membrane-disordering action of ethanol by using deuterium nuclear magnetic resonance (2H-NMR) and fluorescence spectroscopy. Specifically, the effects of ethanol were measured on the 2H-NMR spectra of di(perdeuteropalmitoyl)phosphatidylcholine (DPPC-d62) and on the steady-state emission anisotropy of diphenylhexatriene (DPH) incorporated into hydrated egg phosphatidylcholine (eggPC)/cholesterol dispersions. Analysis of the 2H-NMR spectra of DPPC-d62 incorporated into eggPC liposomes showed that the addition of cholesterol up to 30 mol% enhanced the ability of ethanol to disorder methylene groups all along the phospholipid acyl chains. This effect was somewhat greater toward the terminal methyl groups. However, above 30 mol% cholesterol, the bilayer-disordering action of ethanol on both the upper and lower portions of the acyl chains decreased to an apparent constant change up to the highest cholesterol content examined (50 mol%). Analysis of the fluorescence anisotropy of DPH, on the other hand, suggested that cholesterol attenuated the ability of ethanol to disorder the bilayers, which is in agreement with a previous EPR study [Chin and Goldstein, Mol Pharmacol 19: 425-431, 1981]. Re-analysis of our previous fluorescence anisotropy results with DPH incorporated into dispersions of brain-lipid extracts as a percent change [Johnson et al., Mol Pharmacol 15: 739-746, 1979] indicated that the chemical composition of the lipid bilayers also affects the apparent ability of cholesterol to modulate the membrane-disordering action of ethanol, because the addition of cholesterol to brain-lipid extracts had no significant effect on the membrane-disordering action of ethanol. Given the greater likelihood that the 2H-NMR probes accurately monitor bulk phospholipid properties, some caution is required in the analysis of the membrane disordering actions of drugs using EPR and fluorescence spectroscopy. PMID- 1510725 TI - Human kidney thiopurine methyltransferase. Photoaffinity labeling with S-adenosyl L-methionine. AB - Thiopurine methyltransferase (TPMT) catalyzes the S-methylation of heterocyclic and aromatic sulfhydryl compounds such as the thiopurine drug 6-mercaptopurine (6 MP). TPMT activity in human tissue is regulated by a common genetic polymorphism, and "pharmacogenetic" variation in TPMT activity is an important factor in individual differences in thiopurine drug metabolism, toxicity and therapeutic efficacy. Human renal tissue contains two isozymes of TPMT, Peak I and Peak II, that can be separated by ion exchange chromatography. Our experiments were performed to determine whether S-adenosyl-L-methionine (Ado-Met), the methyl donor for the TPMT reaction, could be used as a photoaffinity ligand for these isozymes as one step in the study of the molecular basis for the TPMT genetic polymorphism. When [3H-methyl]Ado-Met and partially purified preparations of either isozyme of human kidney TPMT were exposed to ultraviolet light at 254 nm, followed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis, a 35 kDa protein was the predominant species that was radioactively labeled. The same 35 kDa protein was photoaffinity labeled with [14C-carboxyl]Ado-Met, demonstrating that labeling involved covalent binding of Ado-Met rather than methylation of the protein. TPMT enzymatic activity co-eluted with the 35 kDa protein during sequential DEAE ion exchange, gel filtration and hydroxylapatite chromatography. Inhibitors of TPMT enzymatic activity including S-adenosyl-L-homocysteine, sinefungin, 6-methylmercaptopurine and 3,4-dimethoxy-5-hydroxybenzoic acid inhibited photoaffinity labeling of the 35 kDa protein in preparations of both TPMT Peak I and Peak II isozymes in a concentration-dependent fashion, as did 6 MP, the methyl acceptor substrate for the TPMT reaction. All of these results were compatible with the conclusion that the 35 kDa protein was TPMT. Photoaffinity labeling of TPMT with [3H]Ado-Met should make it possible to purify the enzyme to homogeneity and to study amino acid sequences at or near its active site. PMID- 1510726 TI - Suicide inhibitors of cytochrome P450 1A1 and P450 2B1. AB - The inhibition of the P450 1A1 dependent de-ethylation of 7-ethoxyphenoxazone (7EPO) and the P450 2B1 dependent de-pentylation of 7-pentoxyphenoxazone (7PPO) by 1-ethynylnaphthalene (1EN), 2-ethynylnaphthalene (2EN), 1-ethynylanthracene (1EA), 2-ethynylanthracene (2EA), 9-ethynylanthracene (9EA), 2-ethynylphenathrene (2EPh), 3-ethynylphenanthrene (3EPh), 9-ethynylphenanthrene (9EPh), 1 ethynylpyrene (1EP) and 2-ethynylpyrene (2EP) was studied in hepatic microsomal preparations from rats. Although all of the polycyclic aromatic acetylenes studied inhibited the dealkylation of 7EPO or 7PPO, only some of the acetylenes produced a mechanism-based irreversible inactivation (suicide inhibition) of the P450 dependent dealkylation of 7EPO or 7PPO. Of the molecules tested, only 1EP, 1EN, 2EN, 2EPh and 3EPh were effective suicide inhibitors of the P450 1A1 dependent de-ethylation of 7EPO and only 1EN, 2EN, 1EA and 9EPh were effective suicide inhibitors of the P450 2B1 dependent de-pentylation of 7PPO. In addition to the size and shape of the polycyclic aromatic ring system, placement of the carbon--carbon triple bond on the ring system was critical for suicide inhibition. In contrast to 1EP, 2EP was not a mechanism-based inhibitor of P450 1A1; 9EPh, but not 2EPh or 3EPh, was a suicide inhibitor of P450 2B1. None of the aryl acetylenes tested produced heme destruction under assay conditions that produced the suicide inhibition of the P450 dependent 7EPO or 7PPO dealkylation activities. Because a precise orientation of the terminal acetylene is required to produce suicide inhibition without heme destruction, acetylenic suicide inhibitors can potentially be used to differentiate between P450 isozymes and to establish some distinguishing geometric features of the active site of these isozymes. PMID- 1510727 TI - Studies on the developmental and adrenal regulation of cytosolic and microsomal epoxide hydrolase activities in rat liver. AB - The present study was undertaken to ascertain developmental profiles of microsomal epoxide hydrolase (mEH) and cytosolic epoxide hydrolase (cEH) enzyme activities in rat liver. During development, mEH activity reached an optimum by 6 weeks of age (63 nmol/min/mg protein). Activities decreased thereafter in both sexes although in adult male liver the activity was twice that measured in adult female liver. Thus, the importance of pituitary maturation was suggested from these findings. Since glucocorticoids have been implicated in the regulation of mEH gene expression the effect of adrenalectomy on mEH activity was investigated in adult male rat liver. The procedure increased mEH activity almost two-fold and the increase was reversed by dexamethasone, but not deoxycorticosterone, administration. With respect to hepatic cEH activity, the developmental profiles indicated that enzyme activity was greatest in rats at 1 week of age (12-15 nmol/min/mg protein) and very little activity was detected beyond 4 weeks of age (approximately 5 nmol/min/mg protein); sex differences in cEH activity were not apparent at any age. Thus, the pituitary appears to be important in the developmental induction of mEH but not cEH. Glucocorticoids appear to provide the major hormonal influence on mEH expression. Thus, the hypothalamus-pituitary adrenal axis is involved in the regulation of mEH but the regulation of the cEH enzyme remains unclear. PMID- 1510728 TI - Lack of enantio-selectivity in the in vitro antitumour cytotoxicity and membrane damaging activity of ether lipid SRI 62-834: further evidence for a non-receptor mediated mechanism of action. AB - SRI 62-834 ([tetrahydro-2-(octadecycloxy)methylfuran- 2 yl]methoxylphosphocholine; CRC 86-05; NSC 614383) is a cyclic antitumour ether lipid (AEL) with a novel, but ill-defined, mechanism of action. AELs are believed to act on membranes and cell signals, but the precise mechanisms of selectivity are unclear. Receptor-mediated mechanisms can often be identified by the differential activity of the individual stereoisomers of a drug. We have therefore compared the R- and S-enantiomers of SRI 62-834 for: (1) cytotoxicity against the human HT29 colon carcinoma cell line using a tetrazolium dye reduction assay and (2) membrane-damaging effects monitored by 51Cr radiolabel release. The tetrazolium assay revealed near-identical mean ID50 values around of 2-3 microM for the R- and S-isomers as well as for the racemic mixture. Moreover, pre- and co-incubation of the cells with the potent platelet-activating factor (1 O-alkyl-2-O-acetyl-sn-glycero-3-phosphocholine;PAF) receptor antagonist WEB 2086BS (3-[4-(chorophenyl)-9-methyl-6H-thieno[3,2- f][1,2,4]triazolo-[4,3-a][1,4] diazepin-2-yl]-1-(4- morpholinyl)-1-propanone) had no effect on the cytotoxicity of either isomer or the racemate. Short-term membrane damage was not evident at low micromolar concentrations and between 139 and 163 microM either lipid was required to release 50% of the incorporated 51Cr label. Again, there was no difference in potency between the enantiomers and the racemate. Coincubation with WEB 2086BS also failed to modulate the membrane-lytic potency of the AELs. These results indicate that the site(s) of cytotoxic action of SRI 62-834 is (are) not stereospecific and also appear to rule out the involvement of a conventional PAF receptor in the mechanism of action of SRI 62-834. PMID- 1510729 TI - Fluorescence quenching of human serum albumin by xanthines. AB - A study of the fluorescence quenching of human serum albumin (HSA) by caffeine, theophylline and theobromine, based on temperature dependence, has shown that it is predominantly static. This quenching mechanism is due to the formation of a xanthine-HSA non-fluorescent complex. The Stern-Volmer equation let us determine the association constants. It seems that the quenching of the protein fluorescence depends on the number and position of the methyl groups. The temperature dependence of the association constant is used to estimate the values of the thermodynamic parameters involved in the interaction of the drugs with HSA. All three binding processes are exothermic and probably hydrophobic, and hydrogen bonds play a significant role in the stabilization of such complexes. The enthalpy and entropy changes observed appear to compensate each other to produce a relatively small Gibbs free energy. PMID- 1510730 TI - Heterogeneity of carboxylesterases in rat liver cells. AB - Rat liver cells were separated into parenchymal cells (PC), Kupffer cells (KC) and endothelial cells (EC). The distribution of carboxylesterases (EC 3.1.1.1) between these cell types was investigated by PAGE and chromatogenic substrate staining, and compared with the results for total liver preparation and individual isoenzymes isolated by chromatofocusing. All of the liver carboxylesterase isoenzymes could be detected in the PC, whereas in both KC and EC only those with isoelectric point (pI) 6.4/6.2 could be detected. Use of carboxylesterase inhibitors like bis-(4-nitrophenyl)phosphate and paraoxon, and organophosphorus compound hydrolase inhibitors like 4-hydroxymercuribenzoate and EDTA confirmed that these esterases were of the carboxylesterase type. PMID- 1510731 TI - Inhibition of enzymes of polyamine back-conversion by pentamidine and berenil. AB - Pentamidine and berenil, clinical antiparasitic amidines, have been found to be potent competitive inhibitors of human spermidine/spermine acetyltransferase (SSAT). Ki values were found to be 2.4 and 2 microM, respectively, with spermidine as substrate. A second enzyme of polyamine back-conversion, murine polyamine oxidase (PAO), was found to be competitively inhibited by pentamidine, with a Ki of 7.6 microM when N-acetylspermine was the substrate. Berenil, on the other hand, was an extremely weak inhibitor (Ki = 120 microM). The implication of the effect of inhibition of polyamine back-conversion on the growth of mammalian parasites is discussed. PMID- 1510732 TI - Protection by cyclosporin A of cultured hepatocytes from the toxic consequences of the loss of mitochondrial energization produced by 1-methyl-4 phenylpyridinium. AB - Cyclosporin A prevented the killing of cultured rat hepatocytes by 1-methyl-4 phenylpyridinium (MPP+). However, in the presence of both cyclosporin and atractyloside, there was no protection. Cyclosporin had no effect on the depletion of ATP or the loss of mitochondrial energization by MPP+. Cyclosporin, however, did prevent the increase in the molecular order of hepatocyte membranes produced by MPP+. These data suggest that mitochondrial de-energization produced by MPP+ is accompanied by a "permeability transition" analogous to that which occurs in vitro in the presence of calcium. By preventing this transition, cyclosporin protects the cells. By antagonizing this action of cyclosporin, atractyloside restores the cell killing. The mitochondrial transition is causally linked to cell killing by a mechanism that increases the molecular order of the hepatocyte plasma membrane. PMID- 1510733 TI - Monoclonal antibodies against 4-hydroxybiphenyl-UDP-glucuronosyltransferase. AB - Monoclonal antibodies against purified rat liver 4-hydroxybiphenyl UDP glucuronosyltransferase were developed using the hybridoma technology. In immunoblot analysis the antibodies specifically reacted with purified 4 hydroxybiphenyl-UDPGT but not with other purified UDPGT enzyme fractions. One single band was detected with microsomes of rat liver and small intestine but not with microsomes of kidney and lung. The reactive protein was also found in dog and human liver microsomes. It could be shown that there was no increase of immunoreactive protein after pretreatment with phenobarbital or 5,6-benzoflavone. This supports the hypothesis that more than one 4-hydroxybiphenyl-UDPGT exist in rat liver which are differently inducible. PMID- 1510734 TI - PZ-51 (Ebselen) in vivo protection against adriamycin-induced mouse cardiac and hepatic lipid peroxidation and toxicity. AB - Adriamycin (Adr)-induced cardiotoxicity occurs most likely via an oxidative mechanism of action. Moderation of this activity may result in an improved therapeutic index for this compound. PZ-51, 2-phenyl-1,2-benzoisoselenazol-3(2H) one, is a selenoorganic compound with thiol-dependent, peroxidase-like activity. We tested this compound alone and in combination with N-acetylcysteine (NAC) for its effect on Adr-induced in vivo toxicity in Balb/c mice. These studies demonstrated that PZ-51 protects against Adr-induced lipid peroxidation in heart and liver tissue and Adr-induced toxicity in general, as measured by total serum creatine kinase activity and body weight. PMID- 1510735 TI - Effects of continuous and pulsed 2450-MHz radiation on spontaneous lymphoblastoid transformation of human lymphocytes in vitro. AB - Normal human lymphocytes were isolated from the peripheral blood of healthy donors. One-ml samples containing (10(6)) cells in chromosome medium 1A were exposed for 5 days to conventional heating or to continuous wave (CW) or pulsed wave (PW) 2450-MHz radiation at non-heating (37 degrees C) and various heating levels (temperature increases of 0.5, 1.0, 1.5, and 2 degrees C). The pulsed exposures involved 1-microsecond pulses at pulse repetition frequencies from 100 to 1,000 pulses per second at the same average SAR levels as the CW exposures. Actual average SARs ranged to 12.3 W/kg. Following termination of the incubation period, spontaneous lymphoblastoid transformation was determined with an image analysis system. The results were compared among each of the experimental conditions and with sham-exposed cultures. At non-heating levels, CW exposure did not affect transformation. At heating levels both conventional and CW heating enhanced transformation to the same extent and correlate with the increases in incubation temperature. PW exposure enhanced transformation at non-heating levels. This finding is significant (P less than .002). At heating levels PW exposure enhanced transformation to a greater extent than did conventional or CW heating. This finding is significant at the .02 level. We conclude that PW 2450 MHz radiation acts differently on the process of lymphoblastoid transformation in vitro compared with CW 2450-MHz radiation at the same average SARs. PMID- 1510736 TI - A replication study of human exposure to 60-Hz fields: effects on neurobehavioral measures. AB - The purpose of this study was to reproduce and extend an earlier investigation of the effects of human exposure to combined, 60-Hz electric and magnetic fields. This paper presents the neurobehavioral results. Thirty men participated in one training session and four testing sessions. Subjects were randomly assigned to two groups. The 18 subjects in Group I were exposed (9 kV/m, 20 microT) and sham exposed in two counterbalanced orders. In Group II, half of 12 subjects were exposed (9 kV/m, 20 microT) every session, and the remaining half were sham exposed every session. The study was doubly blinded. Measures of cardiac interbeat interval, event-related brain potentials, and performance were obtained before, during, and after exposures. As in the earlier study, exposure to the combined field resulted in a statistically significant slowing of heart rate, in changes in late components of event-related brain potentials, and in decreased errors on a choice reaction-time task. In addition, field effects on several other measures approached statistical significance. The physiological measures obtained during exposure indicated that effects were greatest soon after the field was switched on, and again when it was switched off. The data indicate that changes in exposure level may be more important than duration of exposure for producing effects in human beings. PMID- 1510737 TI - Residential exposure to 60-Hz magnetic fields from appliances. AB - A model has been developed that permits assessment of residential exposure to 60 Hz magnetic fields emitted by appliances. It is based on volume- and time averaging of magnetic-dipole fields. The model enables the contribution of appliances in the total residential exposure to be compared with that of other sources in any residence under study. Calculations based on measurements reported in the literature on 98 appliances revealed that appliances are not a significant source of whole-body exposure, but that they may be the dominant source of exposure of the body's extremities. PMID- 1510738 TI - Preliminary report: modification of cardiac contraction rate by pulsed magnetic fields. AB - Isolated rat hearts and excised canine cardiac tissues were subjected to pulsed magnetic fields. The fields excited in coils by tandem pairings of sinusoidal pulses were presented at various inter-pair delays and repetition rates. The waveform of the magnetic field was a single or multiple sinusoid followed after a variable delay by another single or multiple sinusoid. Small but reliable increases in the beating rate of rat heart were observed. Similar increases occurred in contraction rates of canine tissues. Both preparations exhibited a contraction-rate dependency on the repetition rate of the paired magnetic pulses: 4.5-6 rep/s for canine tissue, and 20-25 and 40-55 reps/s for rat heart. Flux density thresholds for both preparations approximated 10 mT (100 gauss) rms. PMID- 1510739 TI - Electric fields induced in rat and human models by 60-Hz magnetic fields: comparison of calculated and measured values. AB - The calculated distribution of electric fields induced in homogeneous human and rat models by a 60-Hz magnetic field is compared with values measured in instrumented mannequins. The calculated values agree well with measured values. PMID- 1510740 TI - Dose dependence of acetylcholinesterase activity in neuroblastoma cells exposed to modulated radio-frequency electromagnetic radiation. AB - Radio-frequency electromagnetic radiation (RFR) at 915 and 147 MHz, when sinusoidally amplitude modulated (AM) at 16 Hz, has been shown to enhance release of calcium ions from neuroblastoma cells in culture. The dose-response relation is unusual, consisting of two power-density "windows" in which enhanced efflux occurs, separated by power-density regions in which no effect is observed. To explore the physiological importance of these findings, we have examined the impact of RFR exposure on a membrane-bound enzyme, acetylcholinesterase (AChE), which is intimately involved with the acetylcholine (ACh) neurotransmitter system. Neuroblastoma cells (NG108), exposed for 30 min to 147-MHz radiation, AM at 16 Hz, demonstrated enhanced AChE activity, as assayed by a procedure using 14C-labeled ACh. Enhanced activity was observed within a time window between 7.0 and 7.5 h after the cells were plated and only when the exposure occurred at power densities identified in a previous report as being effective for altering the release of calcium ions. Thus RFR affects both calcium-ion release and AChE activity in nervous system-derived cells in culture in a common dose-dependent manner. PMID- 1510741 TI - Modification of acoustic startle by microwave pulses in the rat: a preliminary report. AB - Single, 1.25-GHz microwave pulses of 0.8- to 1.0-microseconds duration were presented to each of four rats 100 ms before presentation of a startle-inducing acoustic stimulus. This sequential pairing of microwave pulse and acoustic stimulus was found to modify the startle response. At an energy dose to the head of 22-43 mJ/kg per pulse (peak SAR, 23-48 kW/kg), the mean latency to the startle response was longer and the mean amplitude of the response was smaller with respect to control responses that occurred to acoustic stimuli alone. However, at a higher energy dose per microwave pulse in the range of 59-107 mJ/kg (peak SAR, 63-111 kW/kg), the mean latency and amplitude of the startle response were not statistically different from the respective means of control responses. PMID- 1510742 TI - Who should decide about your death? PMID- 1510743 TI - Female mentors in short supply. PMID- 1510744 TI - En bloc radical vulvectomy and lymphadenectomy with modifications of separate groin incisions. AB - A new modification of radical vulvectomy and lymphadenectomy through separate groin incisions involves dissection of the intervening skin bridge and allows an en bloc dissection. The results in 26 women treated with this technique are compared with those of seven treated with separate incisions without an en bloc dissection. All 33 women had squamous carcinoma of the vulva and were treated between 1985-1989. The incidence of advanced disease was high, with nodal metastases present in 52% of cases. Dissection of the tissue beneath the skin bridge did not alter the morbidity of the procedure in terms of the incidence of wound infection, number of units of blood transfused, or duration of hospitalization. The only case of an isolated recurrence in the skin bridge occurred in a woman who did not have an en bloc dissection, although there was no significant difference in the overall local recurrence rate between the groups. Further evaluation with larger numbers is required, but we suggest that an en bloc dissection using separate incisions may reduce the risk of isolated recurrence in the skin bridge, particularly in patients with advanced disease. PMID- 1510745 TI - Enhancement of recovery from psychiatric illness by methylfolate. PMID- 1510746 TI - Decisions for and against resuscitation in an acute geriatric medicine unit serving the frail elderly. AB - Recent studies indicate continuing controversy over the appropriateness of intensive care in various clinical settings, particularly for very young and very old patients. We studied decisions regarding cardiopulmonary resuscitation (CPR) and the associated clinical course in an acute geriatric unit serving the frail elderly. Despite multiple acute and chronic conditions, advanced age, and functional impairment, patients overwhelmingly preferred CPR. The patients with do-not-resuscitate (DNR) orders were more functionally dependent, more acutely and chronically ill, and less likely to participate in the decision regarding CPR. The majority of DNR orders were made by surrogates, while the majority of CPR directives were made by the patients themselves. Other forms of acute and supportive care, such as parenteral antibiotics, artificial feeding, and transfusions were not withheld from the DNR patients unless a separate decision to limit a specific treatment was undertaken following consultation between the attending physician and the patient or family. Acuity of illness greater than two SDs above the unit mean and the presence of a surrogate decision maker predicted the majority of DNR orders. Length of stay averaged 28 days for all unit patients, 24 days for patients choosing CPR, and 46 days for patients with DNR orders. The four patients who were resuscitated but died stayed an average of 25 days, while the two survivors of resuscitation stayed 20 and 53 days, respectively. The findings indicate that patients and their families considered appropriate clinical criteria including severity of illness when making their decisions about CPR. Nevertheless, the majority chose to be resuscitated in the event of an arrest. Further studies are needed to explore medical decision making by elderly inpatients and their surrogates and to describe the associated clinical course. PMID- 1510747 TI - Hospitalization for heart failure. PMID- 1510748 TI - Depression after the death of a spouse. PMID- 1510749 TI - Oral tolerance and collagen arthritis. PMID- 1510750 TI - Radiation colitis is another mimic of chronic inflammatory bowel disease. PMID- 1510751 TI - Deprivation and general practitioner workload. AB - OBJECTIVES: To examine general practitioner consultations by demographic and socioeconomic variables and to derive a method of measuring the impact of relative deprivation on general practitioner workload. DESIGN: The study was based on general practitioner consultations reported in the general household surveys of 1983-7, covering a sample of 129,987 individuals in Great Britain. Odds ratios for general practitioner consultations were obtained for selected variables among children (0-15 years), men (16-64), women (16-64), and elderly people (greater than or equal to 65). These were then used to derive deprivation indices specific to electoral wards for use in general practice. SETTING: Great Britain, with particular findings illustrated by English electoral wards and the conurbations of London, Manchester, Merseyside, and the West Midlands. RESULTS: Council tenure increased the likelihood of consultation significantly in all four groups. Odds ratios were raised in children, men, and women with no access to a car. Birth in the New Commonwealth or Pakistan yielded high odds ratios in men, women, and elderly people but not in children. Marginally increased consultation rates were evident in the manual socioeconomic groups in women, elderly people, and children with a single parent mother. The deprivation indices for general practice derived using these odds ratios varied substantially among English electoral wards with, for example, anticipated general practitioner consultations in the electoral ward of Hulme, Manchester, being 24% higher than the average ward in England as a result of local attributes, and consultations in the Cheam South ward of Sutton, London, 11% lower than average. CONCLUSION: This deprivation index for general practice overcomes several shortcomings expressed about the underprivileged area score, which has been adopted in the 1990 contract as a basis for allocating deprivation supplements to general practitioners. The proposed index can be applied nationwide. PMID- 1510752 TI - Indications for distal arterial reconstruction in the presence of palpable pedal pulses. PMID- 1510753 TI - Air pollution and cancer risk. PMID- 1510754 TI - The clinical evaluation of hairy cell leukemia. PMID- 1510755 TI - Modeling blood pressure profiles. PMID- 1510756 TI - Cigarettes and addiction. PMID- 1510757 TI - Effect of increased hydration and removal of bone fat on a method for determination of bone density. PMID- 1510758 TI - ASHP guidelines on pharmacists' relationships with industry. PMID- 1510759 TI - Vaccine coverage: recent trends and future prospects. AB - OBJECTIVE: To assess the feasibility of achieving the target of 95% coverage for the childhood immunisation schedule by 1995 and to determine the influence of sociodemographic factors and information systems on recent trends. DESIGN: Analyses of trends in quarterly vaccination data for diphtheria, pertussis, and measles in health districts between February 1988 and February 1991. SETTING: District health authorities in England and Wales, and health and social services boards in Northern Ireland. SUBJECTS: Cohorts of children whose youngest member had reached the target age of 18 months for receiving the third doses of diphtheria and pertussis vaccines and 2 years for receiving measles vaccine. RESULTS: Predicted coverage levels for mid-1995 were in excess of 95% for diphtheria, pertussis, and measles vaccines. In the 118 districts that continuously reported between February 1988 and February 1991 the increase in coverage was 6% for diphtheria and 13% for pertussis and measles vaccines. 1991 coverage depended primarily on 1988 coverage. The additional effects of deprivation, change in computer system, and child population size achieved at most only marginal statistical significance. CONCLUSIONS: The government's target of 95% coverage by 1995 is realistic, although projections should be viewed with caution. Several national vaccination initiatives are likely to have contributed to the recent steady increase in coverage. Updating and validation exercises are likely to improve recorded coverage. PMID- 1510760 TI - Humanities training in surgery education. PMID- 1510761 TI - Lupuslike syndrome associated with simvastatin. PMID- 1510762 TI - Excess mortality associated with diuretic therapy in diabetes mellitus. PMID- 1510763 TI - Solving the problems with patient controlled analgesia. PMID- 1510764 TI - Establishment of pregnancy after removal of sperm antibodies in vitro. PMID- 1510765 TI - Impacted fractures of the femoral neck. PMID- 1510766 TI - Thecoperitoneal shunt for syringomyelia. PMID- 1510767 TI - Cot death biochemistry and pathology. PMID- 1510768 TI - Recurrence of pituitary adenoma after transcranial surgery. PMID- 1510769 TI - Adrenocortical suppression presenting with agitated depression, morbid jealousy, and a dementia-like state. PMID- 1510770 TI - Eating disorders among Asian girls in Britain. PMID- 1510771 TI - Demonstrating an increased incidence of pelvic lymph node metastases in the younger age group. PMID- 1510772 TI - Fetal alcohol syndrome. PMID- 1510773 TI - Coping with grief. PMID- 1510774 TI - Complications following intravenous bolus cyclophosphamide therapy. PMID- 1510775 TI - Inconsistent coding of race and ethnicity in infants. PMID- 1510776 TI - Plea for a new specialty, Thanatology. PMID- 1510777 TI - FBI's case for genetics. PMID- 1510778 TI - Mechanism of Terson syndrome. PMID- 1510779 TI - Reply to the letter of Harlan and Davey, PAIN, 47 (1991) 245. PMID- 1510780 TI - Yates's correction for continuity and the analysis of 2 x 2 contingency tables. PMID- 1510781 TI - The 'gag rule'. PMID- 1510782 TI - Brain abscess after sclerotherapy. PMID- 1510783 TI - Diagnosis of amyotrophic lateral sclerosis. PMID- 1510784 TI - Goldenhar's syndrome. PMID- 1510785 TI - [Thrombolytic therapy in resuscitation]. PMID- 1510786 TI - Exogenous administration of IL-1 alpha inhibits active and adoptive transfer autoimmune diabetes in NOD mice. AB - Diabetes susceptibility in non-obese diabetic (NOD) mice may involve immune dysregulation resulting from cytokine deficiencies. The cytokine IL-1 plays a role in various immune as well as endocrine responses and may be hypoexpressed in NOD mice. Treatment with low levels of exogenous IL-1 alpha for 22 weeks prevented the naturally occurring insulitis and diabetogenic process in NOD mice during and at least 33 weeks after cessation of IL-1 alpha treatment. Treatment with IL-1 alpha also inhibited insulitis and hyperglycemia induced by adoptive transfer of pathogenic, polyclonal CD4+8- T cells. Even after islet-cell destruction, IL-1 alpha injections in diabetic NOD mice normalized plasma glucose levels when administered in combination with insulin, whereas equivalent levels of IL-1 alpha alone did not. Our studies support the hypothesis that IL-1 alpha suppresses autoimmune diabetes and hyperglycemia in NOD mice by pleiotropic effects on both immune and metabolic systems. Thus, IL-1 treatment could clinically be an effective immunotherapeutic modality for autoimmune diabetes mellitus by suppressing early disease progression or normalize plasma glucose levels when insulin is present. PMID- 1510787 TI - Monoclonal anti-tumor necrosis factor antibody renders non-obese diabetic mice hypersensitive to irradiation and enhances insulitis development. AB - In attempt to evaluate biological roles of tumor necrosis factor (TNF), we studied the effects of anti-TNF mAb in non-obese diabetic (NOD) mice. Anti-murine TNF mAb rendered NOD mice hypersensitive to the lethal effects of radiation and prevented the reconstitution of lethally irradiated mice with adoptively transferred lymphocytes. While TNF-alpha reduced the incidence of diabetes development in the adoptive transfer system even when given 6 days post-transfer, mAb to TNF could not reduce or increase the incidence of diabetes compared to control mice. Administration of TNF-alpha for 4 or 8 weeks significantly reduced the incidence of spontaneous insulitis in NOD mice, while anti-TNF mAb given for 8 weeks increased the incidence of insulitis significantly. PMID- 1510788 TI - Thanatology: a new clinical specialty to help confront death. AB - The complexities, widespread ramifications and uncertainties surrounding decisions dealing with the process of dying call for a specialty of clinical thanatology. The need for such a specialty grows out of medical technological progress, which has permitted the prolongation of life without parallel guidelines for its termination. The further functions and roles of a thanatologist would evolve with the passage of time. PMID- 1510789 TI - Hormone receptors and glioma cell growth. PMID- 1510790 TI - Temporal studies on the tissue compartmentalization of bone sialoprotein (BSP), osteopontin (OPN), and SPARC protein during bone formation in vitro. AB - To study the role of noncollagenous proteins in bone formation, the synthesis and tissue distribution of BSP (bone sialoprotein), OPN (osteopontin) and SPARC (secreted protein acidic and rich in cysteine) were analyzed using pulse-chase and continuous labeling protocols during bone formation by cultures of rat calvarial cells. Following a 1 h labeling period with [35S]methionine or [35SO4], radiolabeled BSP was rapidly lost from the cells and appeared transiently in the culture medium and in a 4 M GuHCl extract (G1) of the mineralized tissue. Coinciding with the loss of BSP from these compartments, radiolabeled BSP increased in demineralizing, 0.5 M EDTA extracts (E) of the bone, in a subsequent GuHCl extract (G2), and in a bacterial collagenase digest (CD fraction) of the extracted tissue, over a 24 h chase period. In comparison, the 55 kDa form of OPN, with a small amount of the 44 kDa OPN, was secreted almost entirely into the culture medium. Most of the 44 kDa OPN, together with some 55 kDa OPN, accumulated rapidly in the E extract but could not be detected in either G extract or in the CD fraction. SPARC appeared transiently in the G1 extract, but was otherwise quantitatively secreted into the culture medium from where it was lost by complexing and/or degradation. When cultures were continuously labeled over a 12 day period with [35S]methionine, radiolabeled BSP and 44 kDa OPN accumulated in the E extract together with a small amount of SPARC. Some radiolabeled BSP also accumulated in the G2 extract. From the relative incorporation of [35SO4] over the same time period, a time-dependent loss in sulphate from the BSP was evident. Using a 24 h pulse-labeling protocol, the amount of radiolabeled BSP and OPN in the E extract and the BSP in the G2 extract were not altered significantly over a 12-day chase period. These studies demonstrate that the 44 kDa OPN and most of the BSP are rapidly bound to the hydroxyapatite crystals where they may regulate crystal formation and growth during bone formation. Some BSP is deposited in the osteoid and appears to become masked by the formation of hydroxyapatite, indicating a potential role for this protein in epitactic nucleation of hydroxyapatite crystal formation. PMID- 1510791 TI - Anti-AIDS therapy: an update. AB - This review first examines AIDS as regards its historical aspects and current situation. Attention focuses on some basic etiopathogenic characteristics of this disease. After this point, the main pharmacological aspects are examined and, in particular, attention is paid to the most two interesting targets for pharmacological therapy. Lastly, the dynamic and kinetic profiles of the most promising compounds for therapeutic application are considered. PMID- 1510792 TI - 3,5-Diphenyl-1H-pyrazole derivatives. IX. 2-substituted 4-phenyl-5-(3,5-diphenyl 1H-pyrazol-1-yl) pyrimidines with platelet antiaggregating and other activities. AB - The synthesis of 2-substituted 4-phenyl-5-(3,5-diphenyl-1H-pyrazol-1 yl)pyrimidines 4 a-e by reaction of 1-(1-dimethylaminomethylene-2-oxo-2 phenylethyl)-3,5-diphenyl-1H-pyrazol e with acetamidine, benzamidine, guanidine, guanidinaecetic acid and creatine, respectively, is described. The alpha aminoacid derivatives 4 d and 4 e gave a series of amides 7 by coupling with primary or secondary amines in dimethylformamide (DMF) solution in the presence of diphenyl-phosphorylazide (DPPA) and triethylamine. Some compounds 4 and 7 showed a platelet antiaggregating activity in vitro superior or comparable to that of acetyl-salicylic acid, as well as moderate antihypertensive, local anesthetic, analgesic and antiinflammatory activities in rats and mice. PMID- 1510793 TI - Synthesis and evaluation of antimicrobial activity of new 4-nitroso and 4 diazopyrazole derivatives. AB - Some N-(pyrazol-5-yl)-2-nitrobenzamides, variably substituted in the pyrazole nucleus as well as in the amidic group, were reacted in acetic acid media with potassium nitrite and hydrochloric acid. The different chemical behaviour of the reacted pyrazole derivatives in relation to the substitution pattern in both the pyrazole nucleus and the amidic group, was observed. All compounds isolated from the reaction mixtures (4-nitroso, 4-nitro, 4-diazo and 4-chloro derivatives) were evaluated by the agar diffusion method for their "in vitro" growth inhibitory activity against Candida albicans (our collection), Candida tropicalis ATCC 13803, Saccharomyces cerevisiae ATCC 36375, Escherichia coli ATCC 25922, Staphylococcus aureus ATCC 25923 and Pseudomonas aeruginosa ATCC 27853. The 1 methylpyrazole derivatives showed larger inhibition zones than the 1-phenyl ones in the antimicrobial tests. PMID- 1510794 TI - Antimicrobial and genotoxic activities of N-substituted 2,2' dicarboxamidodiphenyldisulfides. AB - This paper describes the in vitro evaluation of antibacterial, antifungal and genotoxic activities of a series of 2,2'-dicarboxamidodiphenyldisulfides. All the studied compounds exhibited antibacterial activity against Bacillus subtilis. Most compounds were also active against Staphylococcus aureus. Several compounds were active against Saccharomyces cerevisiae and, in most cases, also against Candida tropicalis. No effects were observed against Escherichia coli or Aspergillus niger. Antimicrobial activity turned out to be affected by the substituent in the benzene ring and structure-activity relationships were found. The antibacterial and antifungal activities of the studied derivatives were compared with those of the corresponding 1,2-benzisothiazolin-3-ones and in some cases strong differences were observed. None of the tested compounds contained alerting groups or showed genotoxic properties. PMID- 1510795 TI - 1-Acylaminoimidazoles synthesis and antimicrobial activity. AB - Several new 1-acylamino-2-alkyl-4-arylimidazoles were synthesized. The compounds were obtained by reaction of N1-acylacetamidrazones and alpha-bromoketones. The antimicrobial activity of the prepared compounds was tested. PMID- 1510796 TI - Synthesis and antimicrobial activity of 1,3,4-triaryl-2-azetidinones. AB - A set of substituted 1,3,4-triaryl-2-azetidinones were synthesized and characterized. Their antimicrobial activity, against Gram+ and Gram- bacteria and Fungi, was tested. The compounds 23 and 30 showed remarkable activity against Pseudomonas aeruginosa. PMID- 1510797 TI - Development of absorption furosemide prodrugs: synthesis, in vitro and in vivo evaluation. AB - Six acyloxymethyl esters of Furosemide were synthesized and the structures were determined by chemical and spectroscopic methods. Lipophilicity parameters were analysed by high performance liquid chromatography (HPLC). Hydrolysis performances in human plasma and intestinal fluids anticipate their properties as absorption prodrugs of Furosemide. A bioavailability study carried out with 8 male Wistar rats with one of the synthesized prodrug (acetyloxymethyl 4-chloro-N furfuryl-5-sulfamoylanthranilate) showed a greater absorption in relation to Furosemide. The percentages of mean urinary recovery of Furosemide for the prodrug and for the standard solution of the drug were 20.84 and 14.36 respectively. The doses were 10 mg/Kg in Furosemide. The analytical determinations of Furosemide in biological fluids were done by HPLC. PMID- 1510798 TI - Cytotoxic and DNA binding properties of aminoalkyl derivatives of di- and triazaphenanthrenes. AB - A series of mono- and dicationic derivatives of various di- and triazaphenanthrenes were synthesized and evaluated against both wild-type and amsacrine-resistant P388 leukemia in vitro. Monocationic derivatives of the fully aromatic benzo[c][1,8]naphthyridine chromophore showed moderate and equal cytotoxicity in both cell lines, suggestive of efficacy against both the alpha and beta isozymes of mammalian DNA topoisomerase II. Derivatives of both the benzo[c][1,8]naphthyridine and benzo[c][1,8]naphthyridine-3(4H)-one chromophores also showed significant in vivo activity against wild-type P388 leukemia. PMID- 1510799 TI - Photodynamic effects of a cationic mesosubstituted porphyrin in cell cultures. AB - The photobiological activity of mesotetra (4N-methylpyridyl) porphine (T4MPyP) has been studied in a mammalian cell line in vitro. The uptake of T4MPyP to HeLa cells was examined using fluorescence microscopy. Under violet-blue exciting light, a nucleus-selective red fluorescence was detected. The intensity of fluorescence depended on drug concentration and incubation time, with a maximum relative emission at a concentration value of 10(-5) M for 20 min. The photosensitivity of HeLa cells incubated with T4MPyP under previous conditions and subsequently exposed to variable doses of visible light has been examined. Cell toxicity was evaluated as the surviving fraction, using the trypan blue staining test. The extent of cellular damage was found to be dependent on irradiation time, with a lethal damage after 8 min of light exposure. Cellular DNA-photodamage was studied under sublethal conditions (2 min of irradiation) by the use of the micronucleus test. The number of micronuclei, in these conditions, increased with regard to baseline levels. PMID- 1510800 TI - Conformational aspects of poly(dI-dC).poly(dI-dC) and poly(dG-dC).poly(dG-dC) on binding of the alkaloid, berberine chloride. AB - Interaction of berberine chloride with poly(dI-dC).poly(dI-dC) and poly(dG dC).poly(dG-dC) has been studied by various spectroscopic methods. Comparative data on binding parameters, fluorescence enhancement and Tm measurements indicate a stronger binding of berberine to the IC polymer than to the GC one. Conformational changes as monitored by circular dichroic spectra indicate change of the unusual circular dichroism of poly(IC) to a conformation similar to A conformation, while in poly(GC) only a B-conformational change is observed. Extrinsic CD bands developed in the visible absorption region of berberine on interaction with poly(IC) are of much higher intensity compared to poly(GC). It is concluded that berberine induces a conformational change similar to the A conformation on binding to poly(IC). PMID- 1510801 TI - Influence on metastasis of the reduction of major histocompatibility complex (MHC) class I gene with an antisense oligonucleotide. AB - Cell surface MHC H-2K antigens expressed on various types of B16 melanoma cells of C57BL/6 mouse origin were stained by the avidin-biotinylated enzyme complex (ABC) technique. The low metastatic B16F1 cell line, which demonstrates high levels of H-2K antigen, stained strongly, while the high metastatic B16F10 cell line with no H-2K antigen was not stained. Metastatic colonies which developed in lungs after intravenous (i.v.) injection proved to be negative in both cases. Therefore, in consideration of decreased expression of H-2K antigen in the metastatic process both in vivo and in vitro, antisense oligonucleotides against the class I H-2K gene were transfected into B16F1 cells with H-2K antigens. Subsequent immunohistochemical assessment revealed lack of H-2K antigen expression in the cells, but nevertheless they still could not metastasize to lungs when i.v. injected. This may suggest that any link between the two is not directly causal. PMID- 1510802 TI - How immunology was won in Hungary. AB - To mark the occasion of the 8th International Congress of Immunology, this special issue surveys the latest findings from Hungarian immunology. Here, Janos Gergely, president of the Congress, traces the origins and development of immunology in Hungary and describes the joys and sorrows of being an immunologist in Hungary today. PMID- 1510803 TI - Complement research: biosynthesis, genetics, immunoregulatory role and clinical studies. AB - Complementology is one of the major areas of immunological research in Hungary. Here, Andras Falus and colleagues describe studies on the control of biosynthesis of complement components and on the nature and function of receptors in the complement system. PMID- 1510804 TI - Susceptibility to autoimmune disease: a multigenic viewpoint. AB - In Hungary, analysis of genetic predisposition to disease has generally been studied from a multigenic point of view. Alongside markers of the HLA system, other blood groups and allotypes of immunoglobulins and complement components have been studied. These have been correlated with functional parameters in different autoimmune conditions. PMID- 1510805 TI - The pathogenesis of autoimmune disease. AB - The mechanisms of autoimmune pathology are normally described on a disease-by disease basis. Taking a novel angle, Peter Gergely here examines the role of different types of leucocytes across a spectrum of autoimmune diseases, combining the results from a number of Hungarian laboratories. PMID- 1510806 TI - HIV in Hungary. AB - HIV infection in Hungary has not reached the frightening proportions that are currently ravaging other parts of the world. Given this relatively fortunate position and the now clear understanding of the ways in which HIV is transmitted, vigorous public education programmes have been undertaken to minimize the spread of the virus. Here, George Fust outlines these efforts, discusses diagnosis and monitoring of infected patients, and describes HIV research in Hungary. PMID- 1510807 TI - Cellular and humoral suppression in transplantation. AB - Transplantation immunity and tolerance induction are two sides of the same coin. This article describes a couple of very different approaches, one experimental and one clinical, that may improve the understanding of transplantation immunology through analysis of tolerance induction. PMID- 1510808 TI - Clinical applications of phenotypic analysis. AB - The ability to track lymphocyte differentiation and activation via the expression of cell surface marker molecules has had an enormous impact on diagnosis, monitoring and therapy of a wide range of diseases. Here, Katalin Paloczi highlights studies from Hungary on the clinical applications of such analysis. PMID- 1510809 TI - Novel regulators of the humoral immune response. AB - Activation of mature B cells to proliferation and terminal differentiation is a multistep process controlled mainly by macrophages and T cells. However, there is growing evidence that B cells and other factors can also regulate the humoral immune response. Here, Ferenc Uher, Eva Rajnavolgyi and Anna Erdei describe their work on the emerging role of regulatory interactions between subsets of B cells and their soluble products. PMID- 1510810 TI - Functional studies on Fc receptors. AB - Fc receptors (FcRs) are cell surface molecules that recognize and bind to the constant domains of immunoglobulins. In doing so, they enable antibodies to perform several biological functions, by forming a link between specific antigen recognition and FcR-bearing cells. Here, Gabriella Sarmay provides an overview of recent studies on FcRs in Hungarian laboratories, concentrating on their role in selected biological systems. PMID- 1510811 TI - Bcl-2: a repressor of lymphocyte death. AB - The genes and mechanisms that control programmed cell death are currently the subject of intense study. The bcl-2 gene, a repressor of lymphocyte death, is perhaps the best understood of the programmed cell death associated genes. Here, Stanley Korsmeyer provides a brief overview of bcl-2, concentrating on its roles in B- and T-cell development and in oncogenesis. PMID- 1510812 TI - Endothelial cell binding of NAP-1/IL-8: role in neutrophil emigration. AB - In this article Antal Rot calls into question the generally accepted notion that gradients of soluble chemotactic factors are responsible for leukocyte emigration from the circulation into sites of inflammation. He presents an alternative model in which chemoattractants bound to the surface of endothelial cells promote neutrophil adhesion and emigration, while soluble blood-borne attractants inhibit adhesion and emigration. PMID- 1510813 TI - VDJ recombination. AB - The ability of lymphocyte receptor V, D and J gene segments to rearrange generates much of the receptor diversity that is the hallmark of the immune system. Naturally, the mechanisms of immunoglobulin and T-cell receptor gene recombination are of enormous interest. Here, Fred Alt and colleagues review current understanding of the process and speculate on future findings. PMID- 1510814 TI - The origins and early years of IUIS. AB - The International Union of Immunological Societies (IUIS) was born of the global linkages between scientists involved in an exciting intellectual journey of discovery and search for a conceptual framework for regulation, specificity and memory of the immune response. Starting in the 1950s, a dozen of us discussed the need for an international organization; we founded it in 1969. PMID- 1510815 TI - Endotoxin detection. PMID- 1510816 TI - Social immunology. PMID- 1510817 TI - HEV in normal human bronchi. PMID- 1510818 TI - The antagonistic effects of tetrahydroprotoberberines on dopamine receptors: electrophysiological studies. AB - Tetrahydroprotoberberines (THPBs), including (-)-stepholidine ((-)-SPD), (-) tetrahydropalmatine ((-)-THP) and tetrahydroberberine (THB), have been demonstrated to be a new class of DA antagonists in biochemical and neuropharmacological studies. In this paper, the antagonistic action of THPBs was examined by means of single unit recording from nigral DA neuron in chloral hydrate-anesthetized and gallamine-paralyzed rats. Intravenous injection of these compounds could promptly and completely reverse the inhibition of the spontaneous firing induced by DA agonist apomorphine (APO) in a dose-dependent way. Pretreatment with (-)-SPD, (-)-THP or THB could significantly reduce the inhibitory effect of APO and shift the dose-action curve to the right. Besides, the compounds could increase the spontaneous firing of DA neurons. The above results not only strongly support the conclusion that (-)-SPD, (-)-THP and THB are DA antagonists, but also demonstrate that one of their blocking sites is at somatodendritic DA autoreceptors (D-2 receptors). In other words, (-)-SPD did not exhibit any DA agonistic action in this acute electrophysiological study, although its DA agonistic action can be demonstrated in rotational behavior of 6 OHDA-lesioned rats. The dual actions of (-)-SPD, dependent upon different experimental conditions, are discussed. PMID- 1510819 TI - The role of iron in oxygen-mediated toxicities. AB - The transition metal iron is capable of catalyzing redox reactions between biomolecules and oxygen that would not occur if catalytically active iron were not present. Although these biological oxidations (which are known collectively as "oxidative stress") have been implicated in numerous toxicities, the exact role of the iron catalyst remains to be elucidated. This review focuses on our current understanding of the role of iron in oxidative stress, discussing biologically relevant sources, biochemical forms, and reaction mechanisms of iron as a catalyst of biomolecular oxidations. Specific toxicities in which alterations in normal iron metabolism is thought to overwhelm the body's antioxidant defense system are presented, and future treatment regimens involving novel antioxidant drugs are discussed. PMID- 1510820 TI - Assessment of the carcinogenicity of the nonnutritive sweetener cyclamate. AB - The weight of the evidence from metabolic studies, short-term tests, animal bioassays, and epidemiological studies indicates that cyclamate (CHS) is not carcinogenic by itself; however, there is evidence from in vitro and in vivo studies in animals that implies it may have cancer-promoting or cocarcinogenic activity. Epidemiological studies indicate that the use of nonnutritive sweeteners (CHS and saccharin) has not resulted in a measurable overall increase in the risk of bladder cancer in individuals who have ever used these products. No epidemiological information exists on the possible associations of these sweeteners and cancers other than those of the urinary tract. It is recommended that (1) no further studies on the metabolism of CHS to evaluate its carcinogenicity are required since no potentially hazardous metabolites have been appreciably detected in humans; (2) no further animal bioassays to test for the carcinogenicity of CHS by itself are necessary; (3) the studies in rodents that suggest a promotional or cocarcinogenic effect of CHS should be repeated because they cannot be ruled out; (4) because the significance to human health of a positive outcome of such studies is uncertain, additional research aimed at understanding the predictive value for human health of such results and more generic studies to develop well-validated systems that can be relied on in the assessment of cancer-promoting agents are recommended; (5) in populations where CHS continues to be used, epidemiological monitoring should be continued to determine whether there is an increased risk of cancer in humans who are heavy or long-term users or for those observed long after first exposure. In such monitoring, other cancer sites--in addition to the bladder--should be considered. PMID- 1510821 TI - [Determinants of the smoking habit in the city of Pelotas, Brazil]. AB - Although the harmful effects of smoking on health are well documented, this habit continues to be highly prevalent in Latin America. The objective of this study is to evaluate the frequency of this habit and its possible determinants in the adult population of the city of Pelotas, state of Rio Grande do Sul, Brazil, using a simplified methodology. With the use of a cross-sectional design, a probabilistic sample of 1,401 adults was studied; the no-response rate was 11%. Of those interviewed, 54% had never smoked, 14% were former smokers, and 33% were smokers at the time of the study; 16% smoked 20 or more cigarettes daily. Smoking was more frequent in men (44%) than in women (23%). In relation to educational level, the highest prevalence of smoking was among individuals with five to eight years of schooling (39.7%). The study showed that it is possible with a limited investment of time and resources, to evaluate the frequency of smoking in a representative sample of a medium-sized city, yielding data that will be highly useful for preventive campaigns. PMID- 1510822 TI - [Prevalence of mental disorders in adults in Subtiava, Leon, Nicaragua]. AB - The objective of this study was to estimate the prevalence of mental disorders in the Subtiava district of Leon, Nicaragua. Two-stage cluster sampling was used to select 219 families (n = 584 persons). The study was carried out in two phases. In the first, probable mental disorder cases were screened using the Self Reporting Questionnaire. In the second, the diagnoses were confirmed through the Present State Examination questionnaire. The validity and reliability of the questionnaires had been confirmed in a pilot study. The present study was conducted in October and November 1987, when Nicaragua was still immersed in armed conflict. Construction of a family map made it possible to analyze, through the multiple imputation method, the characteristics of persons who were absent at the time of the interviews or who did not respond. The estimated prevalence percentages and their respective 95% confidence intervals were as follows: neurosis, 7.5% (5.2%-9.8%); depression, 6.2% (2.6%-8.1%); reactive crisis, 3.3% (2.6-6.5%); alcoholism, 5.8% (3.9%-8.9%); organic brain syndrome, 3.9% (1.7% 5.2%); psychosis, 0.5% (0.2%-1.6%); and other disorders, 0.7% (0.2%-1.6%). The estimated overall prevalence of mental disorders in the study population was 27.9%. Disorders were more prevalent among men (30.8%) than women (26.3%). It is concluded that these high estimated prevalences are associated with stress caused by the war. PMID- 1510823 TI - Purification and characterization of an extracellular thiol-containing serine proteinase from Thermomyces lanuginosus. AB - An extracellular protease produced by the filamentous fungus Thermomyces lanuginosus has been purified and characterized. The results indicate that the enzyme, which we have called humicolin, is a thiol-containing serine protease with a molecular mass of 38,000 kilodaltons. Secretion of humicolin, which is glycosylated, is tightly regulated by protein substrates. Kinetic characterization has revealed that humicolin activity is highly dependent upon the deprotonation of a group with a pKa of 6.6 and that the enzyme has a specificity for phenylalanine in the P1 position of the substrate. PMID- 1510824 TI - Purification of sn-glycerol-3-phosphate dehydrogenase from Trypanosoma brucei brucei. AB - A protein has been purified from the membranes of bloodstream forms of Trypanosoma brucei brucei. The purified material contained a single polypeptide chain of molecular mass 67 kilodaltons as judged by sodium dodecyl sulfate polyacrylamide gel electrophoresis; under "native" conditions it migrated through a Sephacryl S-300 column with a similar molecular mass. The purified protein catalysed electron transfer from sn-glycerol 3-phosphate to oxygen with the subsequent formation of water. Electron transfer by the purified enzyme to O2 was dependent on the presence of low concentrations of the mediator phenazine methosulfate. This protein is clearly the major membrane-bound sn-glycerol-3 phosphate dehydrogenase, but it also has some characteristics suggestive of the trypanosome alternative oxidase activities. PMID- 1510825 TI - Expression of c-fos and c-myc genes in uterus and nonreproductive organs during the implantation period in the rat. AB - The c-fos and c-myc mRNA levels were investigated in the uterus and nonreproductive organs of rats during the implantation period (from day 5 to 7 of pregnancy). They were determined by densitometric analysis of slot blots and the mean values (n = 4) at a defined age of pregnancy were compared with those observed in nonpregnant control rats (NP group). No significant variations of c fos level were observed in the liver and brain of pregnant rats. In the uterus, the c-fos level decreased, reached a minimum on day 6 (4-fold decrease compared with the NP group), and then increased. The c-fos level significantly increased in the kidney (2- and 2.5-fold on days 6 and 7), and in the lung (2.5-fold on day 7). The c-myc level did not significantly vary in the uterus, liver, and lung. It significantly increased in the kidney (3-fold on day 7) and in the brain (4.1-, 3.8-, and 6-fold, on days 5, 6, and 7). The changes in c-fos and (or) c-myc gene expression in the uterus and nonreproductive organs could be due to sexual steroids and (or) systemic factors from uterine cells or blastocysts. PMID- 1510826 TI - Developmentally regulated troponin C mRNAs of chicken skeletal muscle. AB - Fast and slow/cardiac troponin C (TnC) are the two different isoforms of TnC. Expression of these isoforms is developmentally regulated in vertebrate skeletal muscle. Therefore, in our studies, the pattern of their expression was analyzed by determining the steady-state levels of both TnC mRNAs. It was also examined if mRNAs for both isoforms of TnC were efficiently translated during chicken skeletal muscle development. We have used different methods to determine the steady-state levels of TnC mRNAs. First, probes specific for the fast and slow TnC mRNAs were developed using a 390 base pair (bp) and a 255 bp long fragment, of the full-length chicken fast and slow TnC cDNA clones, respectively. Our analyses using RNA-blot technique showed that fast TnC mRNA was the predominant isoform in embryonic chicken skeletal muscle. Following hatching, a significant amount of slow TnC mRNA began to accumulate in the skeletal (pectoralis) muscle. At 43 weeks posthatching, the slow TnC mRNA was nearly as abundant as the fast isoform. Furthermore, a majority of both slow and fast TnC mRNAs was found to be translationally active. A second method allowed a more reliable measure of the relative abundance of slow and fast TnC mRNAs in chicken skeletal muscle. We used a common highly conserved 18-nucleotide-long sequence towards the 5'-end of these mRNAs to perform primer extension analysis of both mRNAs in a single reaction. The result of these analyses confirmed the predominance of fast TnC mRNA in the embryonic skeletal muscle, while significant accumulation of slow TnC mRNA was observed in chicken breast (pectoralis) muscle following hatching. In addition to primer extension analysis, polymerase chain reaction was used to amplify the fast and slow TnC mRNAs from cardiac and skeletal muscle. Analysis of the amplified products demonstrated the presence of significant amounts of slow TnC mRNA in the adult skeletal muscle. PMID- 1510827 TI - Characterization of two forms of cationic peroxidase from cultured peanut cells. AB - Two forms of cationic peroxidase from peanut cells were differentiated by concanavalin A affinity chromatography. They differed in molecular mass as well as concanavalin A binding, leading to the initial suggestion that they represented two isozymes of peroxidase. However, similar values for the specific activity, Soret absorption, calcium content, and peptide molecular mass were observed for each of the forms. Therefore, the binding and nonbinding fractions most likely represent two molecular forms of cationic peanut peroxidase, rather than two distinct cationic isozymes. The difference between these two forms is discussed in terms of glycosylation. Through the amino acid sequence analysis of the formic acid treated peptide, the cationic isozyme has been shown to be identical in amino acid sequence to the cDNA clone PNC1. PMID- 1510828 TI - Formation of C19 11-hydroxysteroids by porcine Leydig cells. AB - In a previous study, we reported the presence of 11 beta-hydroxyandrostenedione and 11 beta-hydroxytestosterone in testicular vein blood from mature male pigs. Since C19 steroids with an oxygen function at C11 have not been recorded as products of steroid biosynthesis in normal mammalian testes, we have examined their possible production in purified preparations of porcine Leydig cells. Both androstenedione and cortisol were added as substrates in studies using cell incubations of Leydig cells from mature boars (greater than 8 months old). Steroids were recovered from media by solid-phase extraction and separated by reversed-phase high performance liquid chromatography. Peaks corresponding to retention times of authentic standard steroids were seen for both 11 beta hydroxyandrostenedione and 11 beta-hydroxytestosterone from each substrate. Generally, lesser amounts of C19 11-oxosteroids were noted also. Definitive confirmation was made by gas chromatography - mass spectrometry for 11 beta hydroxyandrostenedione in the media. PMID- 1510829 TI - Characterization and localization of large sulfated glycoproteins in the extracellular matrix of the developing asteroid Pisaster ochraceus. AB - In this study techniques commonly used to extract and purify proteoglycans of vertebrates were applied to the embryo of the asteroid Pisaster ochraceus at the early bipinnaria larva stage, a stage in which extensive cell migration is occurring within the extracellular matrix of the blastocoel. Several large sulfated glycoproteins were isolated and shown to consist of protein cores covalently bound to sulfated polysaccharide chains. The polysaccharide chains consisted primarily of neutral sugars and were not susceptible to glycosaminoglycan-degrading enzymes, suggesting that these were not glycosaminoglycans. The sulfated glycoproteins could be fractionated by electrophoresis on sodium dodecyl sulfate-agarose-acrylamide composite gels. Two types of monoclonal antibodies prepared against isolated extracellular matrix of these embryos reacted with two subsets of bands on Western blots of the composite gels. Staining of sections of the embryos with the antibodies showed that the epitopes that they recognized were located throughout the extracellular matrices of the embryos. That these high molecular weight glycoproteins were located within the extracellular matrix of the embryos suggests that they may be involved in the control of morphogenesis and cellular movement. PMID- 1510830 TI - Control of O-glycan synthesis: specificity and inhibition of O-glycan core 1 UDP galactose:N-acetylgalactosamine-alpha-R beta 3-galactosyltransferase from rat liver. AB - The specificity of glycosyltransferases is a major control factor in the biosynthesis of O-glycans. The enzyme that synthesizes O-glycan core 1, i.e., UDP galactose:N-acetylgalactosamine-alpha-R beta 3-galactosyltransferase (beta 3-Gal T; EC 2.4.1.122), was partially purified from rat liver. The enzyme preparation, free of pyrophosphatases, beta 4-galactosyltransferase, beta-galactosidase, and N acetylglucosaminyltransferase I, was used to study the specificity and inhibition of the beta 3-Gal-T. beta 3-Gal-T activity is sensitive to changes in the R-group of the GalNAc alpha-R acceptor substrate and is stimulated when the R-group is a peptide or an aromatic group. Derivatives of GalNAc alpha-benzyl were synthesized and tested as potential substrates and inhibitors. Removal or substitution of the 3-hydroxyl or removal of the 4-hydroxyl of GalNAc abolished beta 3-Gal-T activity. Compounds with modifications of the 3- or 4-hydroxyl of GalNAc alpha benzyl did not show significant inhibition. Removal or substitution of the 6 hydroxyl of GalNAc reduced activity slightly and these derivatives acted as competitive substrates. derivatives with epoxide groups attached to the 6 position of GalNAc acted as substrates and not as inhibitors, with the exception of the photosensitive 6-O-(4,4-azo)pentyl-GalNAc alpha-benzyl, which inhibited Gal incorporation into GalNAc alpha-benzyl. The results indicate that the enzyme does not require the 6-hydroxyl of GalNAc, but needs the 3- and the axial 4 hydroxyl as essential requirements for binding and activity. In the usual biochemical O-glycan pathway, core 2 (GlcNAc beta 6[Gal beta 3] GalNAc alpha-) is formed from core 1 (Gal beta 3GalNAc-R). We have now demonstrated an alternate pathway that may be of importance in human tissues. PMID- 1510831 TI - [Spectrum analysis of the r-r interval using a PC]. AB - Spectral analysis of r-r variability has been recently proposed as a clinical tool to assess the autonomic nervous system function. In this article we present the results obtained using an equipment and an analysis software (based on Maximum Entropy Method) developed in our laboratory. Analyzing the tachograms derived from prolonged ECG registrations of 12 young healthy subjects, 24 to 36 years old (mean 31 +/- 4), we observed the two classic components of the signal: a low frequency component (0.7 +/- 0.2 Hz) and a high frequency component (0.21 +/- 16.6 Hz). As expected, standing, a simple manoeuvre augmenting sympathetic activity, caused a stronger predominance of the low frequency component. We conclude that our method is reliable to evaluate, by means of spectral analysis, rhythmical oscillations of r-r variability. PMID- 1510832 TI - [Effect of insulin-like growth factor I (IGF-I) on Sertoli cell metabolism in the pubescent rat]. AB - The influence of Insulin-like Growth Factor I (IGF-I) on some metabolic functions of Sertoli cells from peripubertal rats was investigated. Sertoli cells were isolated from the testes of 24-day-old animals and cultured at 32 degrees C in Eagle's MEM with or without 1 nM IGF-I. Sertoli cells cultured in the presence of IGF-I showed increased nuclear RNA polymerase activity (+80%) and augmented protein synthesis (+50%). PMID- 1510833 TI - [Chemoprevention of genotoxic damage in lung cells of rats exposed to cigarette smoke]. AB - Male Sprague-Dawley rats were exposed to cigarette smoke (CS) according to a complex protocol which lasted 40 days. Some of the groups were pre-treated with N acetyl-L-cysteine (NAC) by gavage (1 g/kg b.w.) 5 h before each exposure. Bronchoalveolar lavage was performed in each animal at the end of each exposure period in order to recover pulmonary alveolar macrophages (PAM). Cells were identified and counted under the microscope, and the number of micronucleated (MN) and binucleated (BN) PAM was registered. The results showed an increase in the number of MN PAM, which was already evident after 8 days of CS exposure; this increase remained constant after 28 and 40 days of exposure. A significant decrease in the number of MN PAM was observed in the animals pre-treated with NAC. BN PAM were significantly increased after 28 and 40 days of exposure; again, a slight yet not significant decrease was detected in NAC-pre-treated animals. On the whole, this study demonstrates that CS is clearly clastogenic to alveolar macrophages and that NAC can efficiently prevent this cytogenetic damage. PMID- 1510834 TI - [Facilitating and inhibiting effects of the orientation of attention using peripheral cues]. AB - The attentional field resulting from the presentation of peripheral cues; which were either informative or non informative about the position of the imperative stimulus, was studied. Different time intervals between cue and stimulus (120, 300, 600 ms) were used. The results showed facilitation of the response with the informative cue and inhibition with the non informative cue. This happened for the longest cue-stimulus intervals and when the position of the cue and the position of the stimulus were congruent. Also order of cue presentation (i.e., either informative followed by the non informative cue or vice versa) proved important in producing facilitatory and inhibitory effects. PMID- 1510835 TI - [Morphological characteristics of mastocytes in the infertile human testicle]. AB - Mast cells, basophilic elements of the connective tissue, have been studied in numerous researches carried out both in man and animals. Previous studies showed that mast cells have been found in increased number in testis affected by pathology. In the present research morphologic characteristics of the mast cells in human infertile testis have been studied. Testicular biopsies obtained from 49 subjects, aged from 21 to 61 years, have been treated according to the current techniques for transmission electron microscopy. Results showed that it is possible to distinguish at least two types of mast cells: 1) "Interstitial" mast cells, large, round shaped, with great content of large characteristic granules, in relation with the loose connective tissue surrounding capillary vessels and Leydig cells; 2) "Peritubular" mast cells, flattened and relatively poor in granules, trapped in the conspicuous peritubular collagenic layers. These two types of mast cells differ from one another as concerns not only localization, but also general morphological characteristics and number and ultrastructure of cytoplasmic granules. Probably it is possible to establish a relationship between peritubular mast cells trapping and the increased deposition of fibrous connective tissue in the peritubular layers; such a deposition characterizes a lot of testicular pathologies. PMID- 1510836 TI - Calcium oxalate smear layer: mineralogical and crystallographic study. AB - Different methods to reduce dentine hypersensitivity have been tested by means of oxalate treatments. Natural material (20 teeth) and commercial oxalates have been employed. As a result the dentinal tubules are filled by small crystals preventing dental disease. Permeability measurements have been performed in order to quantify results. The composition of the synthetic smear layer produced after oxalate treatment have been investigated by powder diffraction method suggesting calcium oxalate formation. PMID- 1510837 TI - Primary immunodeficiency diseases. Report of a WHO scientific group. PMID- 1510838 TI - Nonhuman primate models for HIV vaccine development. AB - Animal models will be essential in developing a vaccine to protect against human immunodeficiency virus (HIV) infection. While HIV-1 infects great apes, it induces no disease in these species. Some simian immunodeficiency virus (SIV) isolates cause an AIDS-like disease in macaque monkeys. The SIV/macaque model has proven a valuable system for exploring AIDS pathogenesis and assessing strategies for HIV vaccination. Studies in nonhuman primates have shown that a variety of vaccine approaches transiently elicit immunity which can protect against a very small intravenous challenge of cell-free virus. Longstanding immunity which protects against cell-associated or mucosal virus challenge has not yet been achieved. Nonhuman primate models will be essential for achieving this goal. PMID- 1510839 TI - Extraplacental human fetal tissues express mRNA transcripts encoding the human chorionic gonadotropin-beta subunit protein. AB - The glycoprotein hormone human chorionic gonadotropin (hCG) is synthesized in large quantities by the developing placenta, reaching peak concentrations in maternal blood during the late first trimester and early midtrimester of pregnancy. In general it is believed that the alpha-subunit of this dimeric hormone is expressed in pituitary gonadotropes, thyrotropes, and trophoblasts, while the beta-subunit is expressed exclusively by trophoblasts. Studies from our laboratory and other laboratories have shown that some midtrimester human fetal tissues, in addition to the placenta, can synthesize proteins that appear to be very similar to the beta-subunit of hCG. To define precisely the nature of this putative hCG-beta-subunit in extraplacental fetal tissues, we have examined the mRNA from a variety of human fetal and adult tissues using nucleic acid hybridization and reverse transcription-polymerase chain reaction (PCR) methods. Our results demonstrate that midtrimester fetal kidney and adrenal tissues contain hCG-beta mRNA transcripts at concentrations comparable to that of placenta, while fetal lung, brain, muscle, and adult adrenal contain only trace to undetectable levels of hCG-beta mRNA. By restriction endonuclease mapping of PCR fragments from fetal tissue cDNAs, we show that the hCG-beta transcript expressed in midtrimester human fetal organs is a bone fide copy of hCG-beta gene No. 5 of the beta-subunit gene family located on chromosome 19. PMID- 1510840 TI - Characterization of low Mr zona pellucida binding proteins from boar spermatozoa and seminal plasma. AB - A group of low Mr (16 kDa-23 kDa) glycoproteins on ejaculated boar spermatozoa have been shown to have high affinity for homologous zona pellucida glycoproteins (ZPGPs). These ZPGP binding proteins are derived from seminal plasma as shown by their absence from epididymal spermatozoa and their presence in seminal plasma as identified by N-terminal amino acid sequence analysis. They bind to ZPGPs by a polysulphate recognition mechanism similar to that found for proacrosin-ZPGP interactions. The haemagglutination activity of boar seminal plasma is also associated with these low Mr glycoproteins. It is suggested that they play a role in regulating the rate of sperm capacitation and survival in the female reproductive tract. PMID- 1510841 TI - Purification and characterization of vitellogenin and lipovitellins of the sand crab Emerita asiatica: molecular aspects of crab yolk proteins. AB - In the mole crab Emerita asiatica, the main yolk proteins consist of two slow moving lipovitellins (Lv I and Lv II) of glycolipoprotein nature. Lv I cleaves into subunits (MW: 109,000 and 105,000) and Lv II gives rise to six subunits (MW: 65,000, 54,000, 50,000, 47,000, 44,000, and 42,000) in SDS-PAGE (with beta mercaptoethanol). In order to observe the stability of Lv II as well as to achieve better resolution of the proteins, two different buffer systems (Phosphate buffered saline and tris-buffered saline), 40% sucrose, and glass distilled water were used as homogenizing media. Among them, better resolution was achieved with tris-buffered saline and 40% sucrose, and tris-buffered saline seems to be the ideal medium for elution of Lv II. The analysis of biochemical constituents of the major Lv II reveals a percentage composition of 69.325, 27.927, and 2.753 respectively for protein, lipid, and bound sugars. In the I stage embryo, protein comprises about 67.276%, lipid 29.65%, and bound sugars 3.015%. Vitellogenin (Vg) electrophoretically corresponding to the Lv I and Lv II was present in the female haemolymph during the entire period of embryogenesis. The number of subunits (8) of Vg in all stages remained unaltered and their approximate molecular weights were Vg1, 91,000; Vg2, 87,000; Vg3, 83,000; Vg4, 61,000; Vg5, 58,000; Vg6, 45,000; Vg7, 42,000; and Vg8, 38,000. Different proteins present in the embryos (I and IV stage) and the serum obtained from the animal carrying the I stage embryo were separated by gel-filtration in high performance liquid chromatography (HPLC). Sephadex (G-200) gel filtration chromatography was used to purify the Lv II in large quantity. Total lipid extracted from Lv II as well as the embryos belonging to different stages of development were separated into their constituent neutral, glycolipids, and phospholipids, using silicic acid column chromatography. Thin layer chromatography (TLC) was used to isolate the different phospholipids purified from various stages of embryos and Lv II. As many as seven different phospholipids were separated from Lv II and I and IX stage embryos; and whereas thin layer chromatogram of V and VI stage embryos showed six different phospholipids, embryos of VII and VIII stage contained four phospholipid species. Cholesterol, glycolipids, and individual phospholipids isolated from the Lv II and I stage embryo were quantified spectrophotometrically and the results were discussed. PMID- 1510842 TI - Reinvestigation of the ultrastructure of spermiogenesis and the spermatozoon of Hymenolepis nana (Cestoda, Cyclophyllidea), parasite of the small intestine of Rattus rattus. AB - Spermiogenesis in Hymenolepsis nana begins with the formation of a differentiation zone. This is limited at the front by arched membranes, is surrounded by cortical microtubules associated with 12 crested-like bodies, and contains a single centriole made up of doublets. The distal centriole gives rise to a flagellum that grows at the same pace as the cortical microtubules. Migration of the nucleus takes place after the formation of the flagellum. It is followed by the separation of the old spermatid from the residual cytoplasm. The mature H. nana spermatozoon is filiform and lacks mitochondria. The axoneme, of the 9 + "1" pattern of the Platyhelminthes, does not reach the extremities of the spermatozoon. The nucleus is electron dense and is in close contact with the axoneme around which it coils in a spiral making an angle of 10 degrees to 15 degrees with the spermatozoon axis. The cortical microtubules follow a 10 degrees to 15 degrees helicoidal path along almost their whole length, except at their posterior extremity, where they are parallel to the spermatozoon axis. H. nana is distinguished by the early development of 12 crested-like bodies of different lengths and by the existence of a single centriole in the differentiation zone. Such a high number of crested-like bodies had never previously been reported in a cestode. PMID- 1510843 TI - Recovery of penetration ability in protease-treated zona-free mouse eggs occurs coincident with recovery of a cell surface 94 kD protein. AB - Previous studies have demonstrated that protease treatment of zona-free mouse eggs impairs sperm-egg interaction (Boldt et al.: Biol Reprod 39:19-27, 1988) and causes modification of a 94 kD egg plasma membrane protein (Boldt et al., Gamete Res 23:91-101, 1989). In this report, the ability of eggs to recover penetration ability following protease treatment was examined. Zona-free mouse eggs were isolated and treated with either trypsin or chymotrypsin (1 mg/ml, 20 min), then cultured for 0, 3, or 6 hr before insemination. Eggs cultured for 3 or 6 hr displayed significantly higher penetration levels than eggs inseminated immediately after protease treatment, indicating a recovery of penetration ability during the 3 or 6 hr incubation period. The recovery of penetration ability was not blocked by inclusion of cyclohexamide (50 micrograms/ml) during the 3 or 6 hr culture period, indicating that protein synthesis was not required for recovery of fusion ability. Cell surface radiolabeling studies with 125I revealed that a 94 kD cell surface protein was lost immediately following trypsin or chymotrypsin treatment but was found on the egg surface after the 3 or 6 hr recovery period. Recovery of the 94 kD egg surface protein occurred in the presence of cyclohexamide, and metabolic radiolabeling studies with 35S methionine confirmed that synthesis of a 94 kD protein was blocked by cyclohexamide. These results suggest that the recovery of penetration ability after protease treatment of zona-free eggs is due to recovery of the 94 kD cell surface protein, providing further evidence for the involvement of the 94 kD protein in sperm-egg interaction. PMID- 1510844 TI - The kinetics of oocyte activation and polar body formation in bovine embryo clones. AB - The kinetics of polar body formation were examined in parthenogenetically activated, in vitro matured and aged bovine oocytes. Subsequently, the presence or absence of polar body formation was determined in bovine embryo clones. Polar body formation, defined as telophase II, occurred by 1 (13/40, 43%) and 2 h (15/21, 71%) postparthenogenetic activation of metaphase II stage oocytes. Parthenogenetically activated oocytes readily formed pronuclei by 4 h. Some oocytes had chromatin in a highly condensed state at 1, 2, and 4 h postactivation (13/72, 18%). These oocytes often (10/13, 77%) appeared to be "self-enucleated," as the condensed chromatin was found in a membrane-bound extrusion. The phenomenon was most prevalent when oocytes were handled at room temperature (25 27 degrees C). Nuclear transfer procedures were established to bring about synchronous blastomere fusion and oocyte activation conditions. Synchronous conditions were achieved only when oocytes were handled and manipulated at 37-39 degrees C. Embryo clones examined 2 h postfusion did not form a polar body. Conversely, nucleate demi-oocyte controls were at the late telophase II stage of meiosis. The results are discussed in relation to cell cycle effects on bovine nuclear transfer. PMID- 1510845 TI - Effects of protein synthesis on maturation, sperm penetration, and pronuclear development in porcine oocytes. AB - In vitro matured porcine oocytes were used to test the importance of protein synthesis for sperm penetration, the second meiotic division, and pronuclear development. Experiments were carried out to measure rates of protein synthesis in the presence of protein synthesis inhibitors (35 microM or 350 microM cycloheximide or a combination of inhibitors) (study 1); to test for sperm penetration and pronuclear development when protein synthesis was inhibited during fertilization (study 2); to test for oocyte meiosis, sperm penetration, and female and male pronuclear development when protein synthesis was inhibited during maturation (oocyte maturation in vitro with addition of inhibitor at 0, 24, or 36 hr of culture) (study 3); and to analyze the changes in the pattern of protein synthesis during these phases. Sperm penetration, oocyte meiosis, and female pronuclear development were not affected by the total inhibition of protein synthesis during fertilization. By contrast, inhibiting protein synthesis during maturation severely impaired the completion of meiosis and pronuclear development. Although inhibition of protein synthesis after 36 hr of maturation culture did not totally block male pronuclear development (MPN), the rate of MPN formation was lower than for controls (52% vs. 72%, P less than 0.05). However, protein synthesis was absolutely essential between 24 and 36 hr for the formation of MPN after decondensation. This period of maturation coincided with the dominant phase of protein reprogramming in the oocyte. PMID- 1510846 TI - Cauda epididymal sperm interactions with seminal vesicle fluid. AB - The interaction of rat cauda epididymal sperm cAMP-dependent protein kinase (PKA) with seminal vesicle fluid (SVF) proteins was examined. Specific proteins in SVF act as substrates for the sperm cell PKA. The apparent molecular weights of these proteins are 45.0, 31.5, 17.2, 14.7, and 13.3 kDa. The phosphorylation of one low molecular-weight cauda sperm protein is blocked in the presence of SVF. There is no PKA enzyme activity in SVF. The presence of phosphate transfer activity between the sperm cell enzyme and the SVF proteins is species dependent. For example, mouse and rat SVF proteins are efficient phosphate acceptors, but there is no phosphorylation activity when hamster SVF is used as the enzyme substrate. The sperm cell samples were also assessed for membrane integrity. Specifically, cauda sperm cells used in these assays were judged to be intact when examined microscopically using the fluorescent vital dye carboxyfluorodiacetate. Although there was enzyme activity in the supernatants of the rat sperm cell samples, in the protein kinase assay it required three times as much supernatant volume (compared with intact cell sample volume) to measure the activity. Supernatant enzyme activity did not increase with washing, indicating that the cells were not damaged by this procedure. The enzyme itself does not adhere to the sperm cells, so the PKA enzyme activity is most likely oriented on the external surface of the sperm cell. PMID- 1510847 TI - Functional properties of caltrin proteins from seminal vesicle of the guinea pig. AB - Caltrin proteins from seminal vesicle content of the guinea pig bind with great specificity to different regions of the spermatozoa. Indirect immunofluorescence studies with polyclonal antibodies showed that caltrin I binds to the head, on the acrosomal cup, while caltrin II binds on the principal tail and the neck. No fluorescence was detected either in the midpiece or in the post-acrosomal area of the head when sperm were exposed to either of the caltrins. Calcium-induced hyaluronidase release, which occurs during the acrosomal reaction, was dramatically inhibited by caltrin I (approximately 85% inhibition). Caltrin II was less effective in preventing the enzyme release (approximately 50% inhibition). Chemical modification of the structure modified the biological activity of the two caltrins. Reduction and carboxymethylation of the cysteine residues diminished the inhibitory activity on 45Ca2+ uptake and reduced the ability of the proteins to react with their antibodies. Removal of the carbohydrate portion by chemical deglycosylation transformed the inhibitor proteins into enhancers of calcium uptake into the spermatozoa. Caltrin proteins from the guinea pig appear to play the same physiological role as bovine caltrin, regulating specifically calcium transport across the spermatozoal membranes related with the acrosome reaction and hyperactivation process. The dual behavior of caltrins to inhibit or enhance Ca2+ uptake enables them to fulfill this function. Nevertheless, molecular mechanisms different from those described for bovine caltrin seem to be involved in the control of the functional activity of the guinea pig caltrins. PMID- 1510848 TI - Subzonal insemination of a single mouse spermatozoon with a personal computer controlled micromanipulation system. AB - A personal computer-controlled micromanipulation system was developed for automatic injection of spermatozoa into the perivitelline space of mouse ova. A pair of three-dimensional hydraulic micromanipulators driven by pulse motors was used for this automatic system. The pulse signals that regulate the motors are initiated by the computer program, and these signals cause the micromanipulator to move the microtool precisely. The computer program was designed to perform the most effective movements of the sperm injection needle used during manual micromanipulation. Prior to the manipulation, the computer locates the tip of the injection needle and the end of the egg-holding pipette in the microscope field using image processing. The trajectory of the injection needle is determined according to these initial positions. Using this robotic system, subzonal insemination with a single mouse spermatozoon was attempted in a total of 143 ova. The sperm insertion was successfully completed in all cases without damaging any of the ova. Spermatozoa treated with ionophore A23187 and those without the treatment were used. The fertilization rate (68.8%) of the ova inseminated with treated sperm was significantly higher than that (37.5%) obtained with the nontreated sperm (P less than 0.05). These findings suggest the feasibility and potential for further applications of a robotic microinsemination system and, in addition, that a higher fertility rate in the subzonal insemination of mouse ova can be achieved with the ionophore treatment of spermatozoa. PMID- 1510849 TI - Structural organization of surface domains of sperm mitochondria. AB - Sperm mitochondria are assembled into an organized sheath surrounding the outer dense fibers and axoneme of the flagellar midpiece. Each mitochondrion is arranged so that its surface faces three different cellular organelles including the plasma membrane, neighboring mitochondria and the outer dense fiber-axoneme complex. In this manuscript we present data on structural differentiations of these three different surface domains of the outer mitochondrial membrane. We demonstrate that the apposed surfaces of adjacent mitochondria are joined by a two dimensional network of studs unique to this domain. By contrast, the surface domain facing the outer dense fiber-axoneme complex exhibits a different, but highly ordered structural organization, evident as a parcrystalline network of parallel stripes; this domain is further distinguished by its exclusive association with a midpiece-specific cytoskeletal complex. These differentiations are not seen on the surface domain of mitochondria which faces the plasma membrane. The implications of the mosaic composition of the outer mitochondrial membrane in the assembly and function of the mitochondrial sheath are discussed. PMID- 1510850 TI - F-actin in acrosome-reacted boar spermatozoa. AB - Biochemical and immunoelectron microscopic methods have been used to analyze the distribution of actin in boar spermatozoa and its state of aggregation before and after acrosome reaction. F-actin was detected on sperm head and tail by electron microscopy using an improved phalloidin probe: incubation with a fluorescein phalloidin complex and an anti-fluorescein antibody, followed by labeling with protein A-gold complex. Gold particles, indicating the presence of F-actin, were localized on the sperm surface of the acrosome-reacted spermatozoa. Specific labeling was localized (1) between the outer acrosomal membrane and the plasma membrane in the equatorial region, (2) between the outer surface of the fibrous sheath and the plasma membrane in the postacrosomal region, (3) around the connecting piece and the neck region, and (4) on the external surface of the fibrous sheath in the principal piece of the tail. Furthermore, after NP-40 extraction, the SDS-PAGE revealed a difference in solubility between reacted and unreacted boar spermatozoa, reflecting actin polymerization. We conclude that most actin in the acrosome reacted boar spermatozoa is polymeric. PMID- 1510851 TI - Multiplane transesophageal echocardiography: latest evolution in an imaging revolution. AB - Multiplane imaging with a rotating phased-array transducer from within the esophagus represents the latest development in transesophageal cardiac ultrasound. Transverse, longitudinal, and all possible intermediate oblique planes are easily obtained from the same transducer with minimal probe manipulation. Three-dimensional conceptualization of complex structures and pathologic conditions is facilitated. The major advantages are a simplified examination procedure and much less patient discomfort than monoplane and biplane probe imaging. PMID- 1510852 TI - The role of transesophageal echocardiography in critical care: UCSF experience. AB - The applications of transesophageal echocardiography (TEE) now encompass the arena of critical care. We reviewed the indications, findings, and outcome of TEE in the critical care setting in a tertiary care hospital and report our experience. Eighty-three transesophageal echocardiograms were performed in 69 critically ill patients for the following indications: endocarditis (43%), embolic source (13%), hypotension (10%), mitral regurgitation (10%), left ventricular function (6%), aortic dissection (4%), prosthetic valve dissection (4%), and other (10%). Findings were unexpected in 21 of 83 studies and led to a change in management in 17%. On the basis of the results of TEE, 22% of patients had further evaluation by a more invasive technique, and 19% of patients had surgical intervention without further study. No significant complications attributable to TEE were noted. We conclude that TEE is a safe and useful diagnostic technique with fairly broad applications in the critical care setting. PMID- 1510853 TI - Sensory blockade for difficult passage of transesophageal echocardiography probes. AB - During transesophageal echocardiography probe passage, airway reflexes are usually obtunded with topical local anesthetics. This technique meets with varying degrees of success. Even partially intact airway reflexes result in coughing, retching, and withdrawal, which may prevent transesophageal echocardiography examination or predispose to life-threatening tachycardia and hypertension. Proper preparation of the patient enhances comfort and helps protect against tachycardia and hypertension as well as reducing the time required for examination. This article outlines specific monitoring issues and offers precautions that are critical to transesophageal echocardiography probe passage. It suggests a premedication regimen and describes methods of sedation. Furthermore, it outlines the afferent innervation of the upper airway and specific techniques of temporary reflex interruption. PMID- 1510854 TI - Intravascular ultrasound imaging of blood: the effect of hematocrit and flow on backscatter. AB - This study evaluates two key parameters influencing the ultrasonic backscatter from blood--hematocrit and flow rate--at 30 MHz in an in vitro flow system. A range of hematocrits from 0 to 50% was studied at a constant flow rate; various flow rates between stagnation and physiologic levels were studied at a constant hematocrit. The relation between backscatter intensity and hematocrit was a convex function with a maximum between a hematocrit of 10% and 20%. In the flow rate studies, the blood backscatter intensity was a maximum at a flow rate of 0 and rapidly decreased at higher flow rates. These in vitro results suggest that blood backscatter intensity is minimally dependent on hematocrit in the physiologic range. However, a dramatic increase in backscatter intensity occurs with stagnant flow, presumably the result of red blood cell aggregation. Clinically, blood backscatter intensity may provide an index for risk of thrombus formation. PMID- 1510855 TI - Two-dimensional color Doppler flow velocity profiles can be time corrected with an external ECG-delay device. AB - Although two-dimensional ultrasound color flow imaging is often considered to be a real-time technique, the acquisition time for two-dimensional color images may be up to 200 msec. Time correction is therefore necessary to obtain correct flow velocity profiles. We have developed a time-correction method in which a specially designed unit detects the QRS complex from the patient and creates a trig pulse that is delayed incrementally in relation to the QRS complex. This trig pulse controls the acquisition of the ultrasound images. A number of consecutively delayed images, with known incremental delay between the sweeps, can thus be stored in the memory of the echocardiograph and transferred digitally to a computer. The time-corrected flow velocity profile is obtained by interpolation of data from the time-delayed profiles. The system was evaluated in a Doppler string phantom test. With this technique it is possible to study time corrected flow velocity profiles without the need to alter existing ultrasound Doppler equipment. PMID- 1510856 TI - Beat-by-beat aortic valve area measurements indicate constant orifice area in aortic stenosis: analysis of Doppler data with varying RR intervals. AB - Gorlin formula calculation of aortic valve area suggests that orifice area increases in patients with aortic stenosis with rising cardiac output. Evidence that aortic orifice area varies was sought in patients with aortic stenosis by analyzing Doppler data beat by beat versus RR interval in 22 patients with spontaneous RR variability. Stroke volume increased in all patients from minimum to maximum RR interval by 129% +/- 19%. Over the same range of RR intervals, assessment of aortic valve area by (A) simultaneous inner and outer continuous wave Doppler signals, or (B) nonsimultaneous RR-matched pulsed wave Doppler from the left ventricular outflow tract and continuous wave Doppler from the aortic valve failed to suggest an increase in aortic valve area. A positive relationship between aortic valve area and RR interval was not consistently observed with the exception of seven out of eight patients with mild to moderate (pulsed wave Doppler/continuous wave Doppler time velocity integral ratio of 0.3 to 0.7) aortic stenosis (p less than 0.05). Beat-by-beat measurements of aortic valve orifice area using Doppler techniques do not suggest that the aortic stenosis orifice varies over a wide range of RR intervals and stroke volumes. PMID- 1510857 TI - Variation in the color Doppler area of a regurgitant jet with changes in the absolute chamber pressure: an in vitro study. AB - The color Doppler appearance of a regurgitant jet depends on jet momentum, determined in part by the pressure difference between the two chambers. However, it is not clear if absolute chamber pressure has an independent effect on jet area. To test this question, an in vitro experiment was performed in which dynamically decaying jets were created with identical initial pressure gradients but five different levels of absolute chamber pressures. At every level of chamber pressure, color Doppler images were recorded with two different transducers (3.5 and 5.0 MHz) and jet areas were measured at four different flow rates (0 to 9.9 cm3/sec). A multilinear regression model was created with jet area as the dependent variable and jet flow rate, transducer frequency, and absolute chamber pressure as independent parameters. Jet area was most strongly predicted by flow rate (univariate r = 0.90) and transducer frequency (r = 0.32). Even after adjusting for these effects, however, a small but significant (p less than 0.0001) effect of absolute chamber pressure on jet area was seen with jet area rising by 0.89 cm2 for each 10 mm Hg increase in absolute chamber pressure (multivariate r = 0.96, p less than 0.0001). We conclude that the color Doppler area of a regurgitant jet is dependent not only on the relative pressure and flow between the two chambers but also on the absolute chamber pressure. PMID- 1510858 TI - Atrioventricular plane displacement and left ventricular function. PMID- 1510859 TI - Utility of transesophageal echocardiography in the diagnosis of aortic conduit endocarditis in patients who have undergone the Cabrol procedure. AB - The Cabrol procedure is being increasingly performed in patients with aortic pathologic conditions. Transesophageal echocardiography can help in the prompt diagnosis of endocarditis in these patients. In this report we present transesophageal echocardiographic features of two patients in whom endocarditis developed after they underwent the Cabrol procedure for ascending aortic aneurysm caused by Marfan's syndrome. PMID- 1510860 TI - Misplaced Greenfield filter: diagnosis by transesophageal echocardiography. AB - A case of accidental placement of a Greenfield filter in the right atrium is described. Transthoracic echocardiography demonstrated the filter but was unable to provide details regarding the exact location of the filter. Transesophageal echocardiography showed the filter to be fixed to the tricuspid anulus. This finding, which was confirmed during surgery, was used to guide the subsequent surgical management. PMID- 1510861 TI - Diagnosis of tumor embolus to the pulmonary artery by transesophageal echocardiography. AB - This article describes a patient with renal cell carcinoma and massive tumor extension into the inferior vena cava who experienced sudden tachypnea and subsequent cardiopulmonary arrest. Transesophageal echocardiography was used to diagnose a massive tumor embolus to the pulmonary artery that was subsequently confirmed at autopsy. Transesophageal echocardiography provided a rapid bedside diagnosis of this unusual entity in an acutely ill patient. This technique may prove more widely applicable in the evaluation of patients with suspected pulmonary embolus, whether neoplastic or thromboembolic. PMID- 1510862 TI - Embolic occlusion of a patent foramen ovale: a cause of false negative contrast echocardiogram. AB - A 74-year-old man who had dyspnea and cyanosis demonstrated venous thrombosis and multiple lung ventilation-perfusion mismatches suggesting pulmonary emboli. Transthoracic echocardiography demonstrated a right atrial mass and a microbubble contrast study did not reveal right-to-left shunt. Transesophageal echocardiography revealed an embolus entrapped in the foramen ovale projecting into the left atrium that was subsequently removed. Embolic occlusion of patent foramen ovale is an important cause of false negative microbubble contrast study. PMID- 1510863 TI - Echocardiographic demonstration of an unusual pulmonary venous pathway in a patient with left ventricular inflow obstruction. AB - A newborn infant with mitral atresia and a restrictive patent foramen ovale had normal pulmonary venous connection to the left atrium demonstrated by echocardiography. However, pulmonary venous blood then coursed through an unusual pathway in the roof of the left atrium into the right atrium. This case illustrates the need for the echocardiographer to be reminded of and then search for unusual drainage pathways in cases of left ventricular inflow obstruction, even when the pulmonary veins connect normally. PMID- 1510864 TI - A five-chambered heart: rare coronary artery anomaly with fistula draining into a separate interventricular cavity. AB - The combination of color flow Doppler imaging, contrast echocardiography, magnetic resonance imaging, and coronary arteriography documented the presence of a right coronary artery fistula that opened into a separate cavity in the anterior part of the interventricular septum in a 32-year-old man. Although a traumatic origin could not be excluded, the abnormality was most likely a congenital anomaly. Because there were no significant symptoms and no signs of hemodynamic burden on the heart, a conservative management was decided and no complications occurred during 3 years of follow-up. So far the literature includes only one similar case described by autopsy findings. PMID- 1510865 TI - Aortopulmonary fistula detected by echocardiography 12 years after aortoplasty for correction of ascending aorta aneurysm. AB - We describe a case of aortopulmonary fistula in which the correct diagnosis was made by transthoracic echocardiography. The transesophageal approach, because of severe aortic dilatation, failed to provide the correct diagnosis, underlining the importance of complete transthoracic and transesophageal studies in the evaluation of aortic aneurysms. PMID- 1510866 TI - Subclavian artery stenosis masquerading as prosthetic aortic stenosis: a potential source of confusion in Doppler evaluation of aortic valve disease. AB - In this case report we describe a patient with a prosthetic aortic valve in whom a high-velocity signal from a right subclavian artery stenosis initially was mistaken for the aortic jet signal. Differences in the shapes of the jets obtained from an apical and right supraclavicular position suggested different origins of these two high-velocity systolic signals. Correct identification of the origin of each signal was possible with pulsed Doppler recordings of the subclavian artery and high pulse-repetition-frequency pulsed Doppler interrogation of the aortic valve. PMID- 1510867 TI - On the process for evaluating proposed new diagnostic EEG tests. AB - Assessment of new technology is an important part of the evolving art of medicine. For a variety of reasons, it is appropriate to restrict clinical applications of new technology to those tests which have been shown to be safe and effective. Efficacy of new EEG technology can be assessed through a variety of standard procedures, generally based on controlled, well organized clinical studies. Scientific reports using new EEG technology all too often fail to meet the standards traditionally expected for such clinical trials. Many such studies were never designed to be clinical trials. Misunderstandings occur when reports of scientific studies and informal clinical series become confused with formal clinical trials of efficacy. Based upon examples given during the 1991 ISBET meeting symposium on discriminant analysis, examples are discussed regarding how well individual kinds of presentations can be used to help clarify the generic clinical efficacy of the presented diagnostic tests. PMID- 1510868 TI - QEEG profiles of psychiatric disorders. AB - While reports of EEG correlates of psychiatric disorders date back five decades, clinical sensitivity of the EEG to psychiatric disorders has been greatly enhanced with the advent of quantitative methods of analysis (QEEG). Using a QEEG methodology known as neurometrics we have identified distinctive electrophysiological profiles associated with different psychiatric disorders. With this method quantitative features are extracted from 2 minutes of artifact- free eyes closed resting EEG data, log transformed to obtain Gaussianity, age regressed, and Z-transformed relative to population norms. Using small subsets of neurometric features, multiple stepwise discriminant analyses were used to construct mathematical classifier functions, the values of which are different for members of different a priori defined diagnostic groups. Using this approach, we have demonstrated high discriminant accuracy in independent replications separating many populations of psychiatric patients from normal as well as from each other, including major affective disorder, schizophrenia, dementia, alcoholism, and learning disabilities, as well as high accuracy of discrimination between known subtypes of depression (unipolar vs bipolar). The use of classification accuracy curves (CACs) which allow one to assess the sensitivity and specificity achieved by the discriminant functions is discussed. In addition, using cluster analysis, neurometric subtypes can be identified in several clinically homogenous populations. Preliminary results suggest that baseline membership in some neurometric subtypes may be highly correlated with response to treatment. PMID- 1510869 TI - QEEG in a public health system. AB - For the past decade the Cuban Neuroscience Center has organized on behalf of the Ministry of Public Health of the Republic, a nationwide Program for the introduction of quantitative EEG (qEEG). This Program has involved a) development of standardized equipment for "paperless" EEG, qEEG and brain topography; b) establishment of a network of 21 laboratories of clinical neurophysiology; c) creation of the specialty of clinical neurophysiology which trains physicians from all provinces in both traditional and quantitative electrophysiological methods; d) introduction of standardized protocols for the collection of clinical and electrophysiological information; e) organization of a national normative and neuropsychiatric database; f) establishment of normative regression equations. Among the special issues discussed are: 1) relationship between traditional and quantitative methods; 2) evaluation of the effectiveness of the technology introduced; 3) use of qEEG in the early detection of brain dysfunction. PMID- 1510870 TI - Measurement processes and spatial principal components analysis. AB - Spatial principal components analysis (SPCA) applied to the ongoing EEG yields factor loadings which, when mapped, consistently reveal symmetrical patterns resembling the spherical harmonics. In this paper, we consider the mechanisms responsible for these characteristic patterns. In doing so, we demonstrate that volume conduction is one of a family of processes capable of generating such patterns with SPCA. It is shown that any series of measurements on a sphere in which the covariance is only a function of measurement site angular separation (shift invariant processes) will yield the spherical harmonics as the eigenvectors or factor loadings of the covariance matrix. Simulations further indicate that this effect is robust and not determined by the geometry of the measurement sites. In situations where shift invariant signals coexist with those generated at specific sites (anatomically specific processes), such as evoked potentials and some artifacts, it is shown that the anatomically specific signals do not influence the eigenvectors of the covariance matrix in a uniform or random fashion. The factors most influenced are those whose symmetry is similar to that of the site specific signal. PMID- 1510871 TI - Neurometrics in cerebral ischemia and uremic encephalopathy. AB - The neurometric method as introduced by John was used to study three groups of patients with cerebral ischemia, three groups of patients with renal disease and an additional normal control group. The traditional neurometric approach was slightly modified: relative band power values were not expressed as a percentage of the total power per derivation but as a percentage of the "global power"; frequency matrices were used in addition to power matrices. From the study of the three groups of patients with one-sided supratentorial ischemia it appeared that sensitivity and specificity are completely satisfactory when using neurometrics in patients with severe ischemia in the middle cerebral artery territory studied within 48 hours of the onset of the stroke. However, in ischemia patients with less pronounced clinical signs and especially in patients without persistent neurological deficit the sensitivity is much lower. In studying dialysed and non dialysed renal patients signs of an (often subclinical) encephalopathy could be detected in approximately 37% of all patients. Follow-up studies of the ischemia patients and the renal patients over a period of several years revealed a parallelism between clinical scores and qEEG scores in the ischemia patients; almost all qEEG improvement occurred in the first three months after the stroke. The qEEG profile of the groups of dialysed patients tended to be more or less stable over a period of several years. PMID- 1510872 TI - Quantitative EEG in elderly depressives. AB - Thirty-one elderly depressive patients were evaluated with topographic, quantitative EEG using relative measures, absolute measures, and computations of interhemispheric asymmetry and interhemispheric coherence in four frequency bands: delta, theta, alpha and beta. Patients were found to have lower than normal delta, higher than normal theta, higher than normal alpha and lower than normal beta values. EEG values were greater over the left than the right hemisphere in theta, alpha and beta bands. Lower than normal anterior interhemispheric coherence was found in all four frequency bands. PMID- 1510873 TI - Unrestricted principal components analysis of brain electrical activity: issues of data dimensionality, artifact, and utility. AB - Principal components analysis (PCA) was performed on the 1536 spectral and 2944 evoked potential (EP) variables generated by neurophysiologic paradigms including flash VER, click AER, and eyes open and closed spectral EEG from 202 healthy subjects aged 30 to 80. In each case data dimensionality of 1500 to 3000 was substantially reduced using PCA by magnitudes of 20 to over 200. Just 20 PCA factors accounted for 70% to 85% of the variance. Visual inspection of the topographic distribution of factor loading scores revealed complex loadings across multiple data dimensions (time-space and frequency-space). Forty-two non artifactual factors were successful in classifying age, gender, and a separate group of 60 demented patients by linear discriminant analysis. Discrimination of age and gender primarily involved EP derived factors, whereas dementia primarily involved EEG derived factors. Thirty-eight artifactual factors were identified which, alone, could not discriminate age but were relatively successful in discriminating gender and dementia. The need to parsimoniously develop real neurophysiologic measures and to objectively exclude artifact are discussed. Unrestricted PCA is suggested as a step in this direction. PMID- 1510874 TI - Frequency domain models of the EEG. AB - The structure of the normal resting EEG crosspectrum SVV(omega) is analyzed using complex multivariate statistics. Exploratory data analysis with Principal Component Analysis (PCA) is followed by hypothesis testing and computer simulations related to possible neural generators. The SVV(omega) of 211 normal individuals (ages 5 to 97) may be decomposed into two types of processes: the xi process with spatial isotropicity reflecting diffuse, correlated cortical generators with radial symmetry, and processes that seem to be generated by more spatially concentrated, correlated sources. The latter are reflected as spectral peaks such as the process. The eigenvectors of the xi process are the Spherical Harmonic Functions which explains the recurring pattern of maps characteristic of the spatial PCA of qEEG data. A new method for estimating sources in the frequency domain which fits dipoles to the whole crosspectrum is applied to explain the characteristics of the localized sources. PMID- 1510875 TI - Subtyping of psychiatric patients by cluster analysis of QEEG. AB - We have previously reported successful classification of patients with a variety of psychiatric disorders, using multiple discriminant functions based upon selected neurometric QEEG variables. In independent replications, these functions accurately separate patients with different DSM-III-R diagnoses from one another and from normals. This capability demonstrates that distinctive and replicable patterns of neurometric abnormalities are correlated with the clinical symptom clusters upon which DSM-III-R diagnostic criteria are based. However, patients with the same clinical diagnoses often respond very differently to the same treatments. Similar symptoms may arise from different pathophysiology. This study explored the 'natural structure' of a population of psychiatric patients in 8 diagnostic categories, using uninformed cluster analysis based upon the same set of neurometric variables found useful in separating each of these categories from normal. This preliminary numerical taxonomic approach reveals that groups of patients in each of these DSM-III-R categories contain subtypes with markedly different pathophysiology; further, patients in different DSM-III-R categories were aggregated together within each cluster, displaying similar pathophysiological profiles. Objective classification based on such physiological measurements may add information useful to improve treatment outcomes. PMID- 1510876 TI - Autoregulation of prostaglandin E2-induced Ca2+ influx in osteoblast-like cells: inhibition by self-induced activation of protein kinase C. AB - In cloned osteoblast-like MC3T3-E1 cells, prostaglandin E2 (PGE2) stimulated 45Ca2+ influx even in the presence of nifedipine, a Ca2+ antagonist that inhibits voltage-dependent Ca2+ channel, in a dose-dependent manner, attaining a maximum at 0.5 microM. Dose of PGE2 above 0.5 microM caused less than maximal stimulation. While PGE2 stimulated the formation of inositol trisphosphate dose dependently in the range between 1 nM and 10 microM. 12-O-Tetradecanoylphorbol-13 acetate (TPA), a protein kinase C (PKC)-activating phorbol ester, which by itself had little effect on 45Ca2+ influx, significantly suppressed the 45Ca2+ influx induced by PGE2 in a dose-dependent manner between 1 nM and 1 microM. 4 alpha Phorbol 12,13-didecanoate, a phorbol ester which is inactive for PKC, showed little effect in this capacity. Staurosporine, a PKC inhibitor, enhanced the PGE2 induced 45Ca2+ influx. On the other hand, dibutyryl cAMP had little effect on the 45Ca2+ influx induced by PGE2. Our data suggest that PGE2 regulates Ca2+ influx through self-induced activation of PKC. These results indicate that there is an autoregulatory mechanism in signal transduction by PGE2, and PGE2 modulates osteoblast functions through the interaction between Ca2+ influx and phosphoinositide hydrolysis in osteoblast-like cells. PMID- 1510877 TI - v-Src induces elevated levels of diglyceride by stimulation of phosphatidylcholine hydrolysis. AB - When Rat-1 cells bearing the ts LA29 mutant of Rous sarcoma virus (Rat1 LA29) are shifted from restrictive to permissive temperature, the pp60v-Src tyrosine kinase is activated and there is an increase in the cellular level of sn1,2 diacylglycerol (DRG) within 30 min which is not accompanied by increased inositol phospholipid hydrolysis. Temperature shift also increases the hydrolysis of phosphatidylcholine (PC), as determined by an increase in the generation of water soluble choline metabolites. Transphosphatidylation studies have shown that this occurs at least in part via a phospholipase D (PLD) catalysed pathway. PMID- 1510878 TI - Mitogen stimulation of T-cells increases c-Fos and c-Jun protein levels, AP-1 binding and AP-1 transcriptional activity. AB - We have analysed the effect of mitogenic lectins on c-Fos and c-Jun protein levels as well as on activator protein-1 (AP-1) binding and enhancer activity in Jurkat T-cells. Both c-Fos and c-Jun protein levels were increased after Con A and PHA stimulation. Since T-cell stimulation increases both intracellular Ca2+ and cAMP levels and activates protein kinase C (PKC), the possible involvement of these intracellular messengers in c-Fos and c-Jun induction was tested. PMA, which directly activates PKC, mimicked the effect of the lectins on c-Fos and c Jun, but elevation of either intracellular Ca2+ or cAMP levels had little or no effect. The mitogen-induced increase of c-Fos and c-Jun immunoreactivity was inhibited by H-7, a kinase inhibitor with relatively high specificity for PKC, and less efficiently by H-8, a structurally related kinase inhibitor less active on PKC, but more active on cyclic nucleotide-dependent kinases. Con A stimulation was found to increase both binding of AP-1 to the AP-1 consensus sequence, TRE, and AP-1 enhancer activity, in Jurkat cells. PMA was also found to increase the AP-1 enhancer activity, whereas elevation of Ca2+ or cAMP had only minor effects. We conclude that stimulation with mitogenic lectins is sufficient to increase both c-Fos and c-Jun protein levels, AP-1 binding and AP-1 enhancer activity in Jurkat cells and that they act via mechanisms that could involve the activation of PKC. PMID- 1510879 TI - Increased phosphorylation of nuclear substrates for rat brain protein kinase C in regenerating rat liver nuclei. AB - Protein phosphorylation catalysed by rat brain protein kinase C (PKC) has been studied in nuclei isolated from normal and regenerating rat liver. Histone H1 and a 40,000 molecular weight protein were hyperphosphorylated at all the explored regeneration times, ranging from 3 to 22 h after partial hepatectomy. Phosphorylation of the two substrates was totally dependent on calcium and lipids and was abolished by low concentration of staurosporine. The observed early change of phosphate content of histone H1 and of the 40,000 molecular weight protein on the time scale of liver regeneration suggests that PKC might be involved in the initial nuclear events leading to cell proliferation. PMID- 1510881 TI - Health promotion at PAHO. PMID- 1510880 TI - Prostaglandin E2 can bimodally inhibit and stimulate the epididymal adipocyte adenylyl cyclase activity. AB - Measurements of prostaglandin E2 (PGE2)-induced adenylyl cyclase activity in membranes isolated from epididymal rat adipocytes revealed inhibition of cAMP production at low concentrations of PGE2 (less than 10 mM) and stimulation at higher concentrations. This biphasic effect of PGE2 was obtained when adenylyl cyclase was stimulated with GTP or NaF. In the presence of forskolin only the inhibitory phase by PGE2 was observed. Sulprostone, a PGE2 analogue, did not affect cAMP synthesis in the presence of either GTP or NaF; however, in the presence of forskolin, it inhibited cAMP production similarly to PGE2. Treatment of the membranes with cholera or pertussis toxin did not alter the biphasic effect of PGE2 on cAMP production. These findings raise the possibility that PGE2 acts through several receptor subtypes which are coupled to GTP binding proteins different from the classical Gi or Gs proteins. PMID- 1510882 TI - Yellow fever in 1989 and 1990. PMID- 1510883 TI - The clinical use of thermocouple thermometry. AB - The development of a clinical thermometry system entails solving both clinical and technical problems. A thermometry system will, in general, be comprised of a temperature transducing element, a mechanism for interrogating the transducer temperature, and a means of interpreting, reporting and recording the measured temperature. Thermocouples are thermometers which report their own temperature, while the parameter of interest is the temperature of the medium. The two key questions which arise are then: (1) is the thermometer correctly reporting its own temperature, and (2) what is the relationship between the medium temperature and the thermometer temperature? In this work some of the important parameters influencing the temperature of the thermometer and the thermal relationship between the thermometer and the medium are investigated. PMID- 1510884 TI - Electrical impedance tomography: prospects for non-invasive control of deep hyperthermia treatments. AB - Electrical Impedance Tomography (EIT) is assessed as a means of monitoring deep hyperthermia treatments in both phantom and in vivo studies. EIT measurements during heating of an inhomogeneous leg phantom show good correlation with internal temperatures measured with invasive probes. Measurements whilst altering the temperature of the stomach contents in volunteers demonstrate the capability of EIT for imaging temperature change at depth in the torso. Significant problems remain to be overcome before EIT can be used in the clinic; however, the technique may be an important additional control factor as a complement to invasive monitoring. PMID- 1510885 TI - Non-invasive thermometry with multi-frequency microwave radiometry. AB - The present status of the development of a non-invasive thermometer based on microwave radiometry at our laboratory is reported. We have developed a model fitting technique combined with a Monte Carlo technique to retrieve temperature depth profiles from multi (4-6)-frequency-band microwave radiometric data along with confidence intervals (2-sigma) of tissue temperatures as a function of depth. In order to make the radiometric technique compatible with the heating, brightness temperatures are measured through a 1 cm thick water bolus. Results of phantom experiments are presented to demonstrate the above capabilities of the method. Numerical simulation studies have shown that 2-sigma intervals would be 1.0 K or less over a 0-4 cm range and 1.4 K at 5 cm from the surface with using a six-band, 1-5 GHz radiometer having brightness temperature resolution of 0.03 K (3 s integration time). The six-band instrument is currently being assembled at our laboratory. PMID- 1510886 TI - Simultaneous estimation of blood flow rate and tissue temperature. AB - A new method for simultaneously estimating blood flow rate and tissue temperature under a RF hyperthermia treatment is presented. In this method the finite element method is used to solve the two-dimensional Laplace equation for a specific absorption rate (SAR) distribution and the two-dimensional bioheat transfer equation for a tissue temperature distribution from the SAR pattern over a cross section of a patient-specific model input from computer tomography images. Blood flow rates used in the temperature distribution computation are determined from basal values given for respective types of tissues and tissue temperatures through an assumed function that is intended to represent the temperature dependence of the blood flow rate. The tissue temperature computation procedure is iterated until the estimated temperature at a given sampling point matches a measured value at that point. This iterative procedure allows one to simultaneously estimate blood flow rate and tissue temperature. This paper describes the numerical method along with results of rudimentary in vivo measurements made in a human brain, where blood flow rate was measured by the single photon emission computed tomography (SPECT) imaging technique and tissue temperature was measured by an invasive probe technique. PMID- 1510887 TI - Comparison of normal respiratory sounds recorded from the chest and trachea at various respiratory air flow levels. AB - Respiratory sounds (RS)s were recorded from the trachea and chest of 10 normal adult subjects at respiratory air flow levels of 1.6, 2.1 and 2.6 l/s using an oral flow transducer, and at approximately 2.1 l/s without the flow transducer. Tracheal RS (TRS) and chest RS (CRS) frequency spectra were generated using Fast Fourier Transform, and the peak, mean and maximum frequency parameters were derived from each spectra. Parametric analysis showed: (i) all three parameters for TRS spectra are significantly higher than those for CRS spectra; (ii) TRSs are on average eight times louder than CRSs; (iii) both TRSs and CRSs are air flow independent over the flow range, though TRSs are significantly modified by the flow transducer while CRSs are not; and (iv) though of similar loudness, inspired and expired RSs (both TRSs and CRSs) have some significant spectral differences. To compare the complex shapes of RS spectra, each spectra was divided into narrow frequency bands (to create a feature set) and principal component analysis was performed on all spectral feature sets. TRSs and CRSs were shown to be independent biological signals with little overlap in their respective spectral characteristics. PMID- 1510888 TI - Energetics of the fibrillating ventricle. AB - We have proposed a new mechanical index, equivalent pressure-volume area (ePVA), as a measure of the total mechanical energy of a fibrillating ventricle. ePVA is an analogue of the pressure-volume area (PVA) of a contracting ventricle and the specific area surrounded by the horizontal pressure-volume line at the pressure of ventricular fibrillation (VF) and the end-systolic and end-diastolic pressure volume relations in the beating state in the pressure-volume diagram. In the isolated, cross-circulated heart preparation, we obtained myocardial oxygen consumption (VO2) during VF and ePVA at various left ventricular volumes in the control, epinephrine, propranolol and hypothermia runs. ePVA was highly linearly correlated with VO2 in all runs (r = 0.95, 0.98, 0.96 and 0.90, respectively). We also determined equivalent heart rate (eHR) as an estimate of the contraction frequency of individual myocytes in a fibrillating ventricle from mechanically unloaded VO2 in beating and fibrillating states. Using both ePVA and eHR, VO2 during VF was estimated and correlated with directly measured VO2. Estimated VO2 almost agreed with measured VO2 in all runs. We conclude that ePVA is a primary determinant of VO2 during VF, and that VO2 of a fibrillating ventricle can be reasonably accounted for by the combination of ePVA and eHR. This paper is a review of our previous studies on the energetics of a fibrillating ventricle. PMID- 1510889 TI - Guidelines for thermometry in clinical hyperthermia. AB - High quality thermometry is needed in hyperthermia to (1) ensure safe delivery of adequate therapy and (2) provide the quantitative information needed to develop prognostic parameters which will aid research into planning and dosimetry. Currently, only invasive thermometry which is subject to several sources of artifact is available to address these requirements. This paper summarizes techniques which have been developed to reduce these artifacts to acceptable levels, outlines quality assurance requirements ensuring good practice in the use of invasive thermometry during clinical treatments and ends with a brief discussion of thermometry requirements for control of various hyperthermia systems. PMID- 1510890 TI - Pharmacokinetics of mitomycin C following hepatic arterial chemoembolization with gelfoam. AB - Twelve mongrel dogs were randomly allocated into two groups using matched paired design. Catheters were inserted into the hepatic artery, hepatic vein and the femoral vein, respectively. In the first group, gelfoam supplemented with mitomycin C (MMC) was injected into the hepatic artery, whereas the second group received a hepatic arterial injection of MMC solution alone. Simultaneous blood sampling from the hepatic and femoral vein at regular intervals was performed. MMC concentrations in plasma was determined using high performance liquid chromatography (HPLC) and the pharmacokinetics of MMC were determined. MMC concentrations in hepatic and femoral veins did not differ and no significant difference in pharmacokinetics was found when comparing MMC administration into the hepatic artery with or without gelfoam supplementation. Thus, our results revealed that gelfoam could not delay the clearance of MMC from the liver. PMID- 1510891 TI - Choledochoplasty by vein grafts in iatrogenic bile duct injuries. AB - The quality of immediate repair of common bile duct injuries with or without tissue loss occurring during elective cholecystectomy is crucial and maybe the sole factor behind future stricture formation with its considerable morbidity and mortality. Successful repair of iatrogenic common bile duct injuries has been achieved by immediate saphenous vein grafts in two patients with cystic duct avulsion, in one patient whose duct was split by a balloon catheter, and in one patient where a segment of the duct was resected. Follow-up for 5 years demonstrated that the grafting remained sound and produced no complications. Consequently, the immediate repair of iatrogenic bile duct injuries using vein grafts deserves consideration. PMID- 1510892 TI - A case of primary squamous cell carcinoma of the liver arising in a solitary cyst. AB - A case of primary squamous cell carcinoma in a pre-existing hepatic cyst is presented. A review of the literature suggests that this rare type of liver tumor tends to arise from solitary, nonparasitic cysts, lined with squamous epithelium. Effective therapy is not available, the prognosis is grave. PMID- 1510894 TI - Liver transplantation in the presence of portal vein thrombosis. PMID- 1510893 TI - Tuberculous pancreatic abscess: a rare condition mimicking carcinoma. AB - We report a rare case of obstructive jaundice caused by a tuberculous abscess in the head of pancreas, mimicking carcinoma. The case was successfully treated by pylorus-preserving proximal pancreatoduodenectomy and antituberculous drugs. PMID- 1510895 TI - Oral cancer diagnosis and delays in referral. AB - Delays at various levels in the management pathway of oral cancer have previously been reviewed. It is a clinical impression that advanced tumours are being misdiagnosed by practitioners and consequently delays in referral are still prevalent. A study was conducted to compare the diagnosis and referral patterns of medical and dental practitioners. The results indicated that despite seeing similar populations of patients with oral cancer, the medical practitioner was better at diagnosing and referring cases early, and noting the relevance of lymphadenopathy. A high index of suspicion is a prerequisite for early diagnosis and referral of patients with oral cancer. The findings of this study highlight the importance of correct diagnosis, and support recent recommendations regarding practitioner education. PMID- 1510896 TI - A three-dimensional soft tissue analysis of 16 skeletal class III patients following bimaxillary surgery. AB - A three-dimensional soft tissue study of the results of surgery in a group of 16 skeletal Class III adult patients following orthognathic surgery was carried out using laser scans (Arridge et al., 1985). The patient group was compared to a control group of the same population. Laser scans were taken prior to surgery, 3 months post-surgery, and at least 1 year after retention. Preoperative comparison to the control groups revealed that the facial disproportion related to both the maxilla and the mandible. Le Fort I advancements resulted in broadening of the lateral aspects of the nose, advancement of the dorsum, and overcorrection of the alar bases. There was a degree of change over the cheeks bilaterally, because of alterations in the general drape of the soft tissues. There was a degree of overcorrection in the female group following mandibular set back but the male group were still more prognathic, when compared to the control group. There was a marked degree of relapse in the mandible from 3 months to 1 year postoperatively, with a resultant anterior movement of the maxillary arch. Laser scanning has proved to be a simple non-invasive method of measuring three-dimensionally, and is a very useful tool in auditing surgical outcome and measuring surgical relapse. PMID- 1510897 TI - Reproducibility of three-dimensional CT-assisted model production in the maxillofacial area. AB - In the mid-eighties, computerised tomography (CT) assisted three-dimensional imaging, and modelling of skull structures was introduced into preoperative diagnosis in maxillofacial surgery. This new method is already being used in the preoperative planning of corrections of post-traumatic defects and craniofacial deformities as well as in tumour surgery and implantology. The aim of the present study was to collect information on the reproducibility of a skull model milled from hardened polyurethane foam, and based on the CT data of a real skull. Thirty one measurements were carried out on the model and on the original skull, leading to the result that the model showed a mean inaccuracy of 1.5 mm. The deviations ranged between 0.0 and 3.6 mm. Generally, the model structures, however, tended to be larger than those of the original. As far as the total of all measurements is concerned, the model deviated from the original skull by 1.6%. A convincing aspect of the model, which cannot be obtained by any other method, is its plasticity and the possibility of 3-D orientation on a lifesize model. However, the study indicates that surgeons using this technique should consider the possible discrepancies between the model and the real skull when making preoperative assessments. PMID- 1510898 TI - An update on recent advances in the understanding of non-neoplastic diseases of the salivary glands. AB - The recent advances in the understanding of the non-neoplastic disorders of salivary glands are summarised in this paper. The common infections are discussed and newer aspects of juvenile recurrent parotitis outlined. The benign lympho epithelial lesion is reviewed in relation to Sjogren's syndrome and the salivary gland pathology seen in relation to infection with human immunodeficiency virus. A range of unusual conditions that may affect the minor salivary glands in particular, and can cause diagnosis dilemmas, is summarised. PMID- 1510899 TI - An investigation of the effect of midazolam on the pain experience. AB - In a randomised, double-blind, cross-over study on 20 healthy human volunteers, the effect of intravenous midazolam on pain tolerance using the 'submaximum effort tourniquet technique' is described. Intravenous midazolam administered in conscious sedation doses was found to significantly reduce the affective and motivational component of the pain experience. PMID- 1510900 TI - Concentration of cefuroxime in mandibular alveolar bone following a single preoperative dose. AB - A pilot study was undertaken on 12 patients undergoing the bilateral removal of impacted mandibular wisdom teeth to determine the level of cefuroxime sodium within the alveolar bone adjacent to the third molar teeth following a single preoperative intravenous administration. The results indicated that a single 1.5 g intravenous bolus injection provided satisfactory alveolar bone concentrations for routine antibiotic prophylaxis at the time of wisdom tooth removal. PMID- 1510901 TI - Blank paper or printed set task forms for retrievable patient notes? AB - Patients' clinical notes made at review appointments following removal of third molars under a general anaesthetic at five Mersey Hospitals have been compared with those formed from the recording of the findings of preselected tasks. Consistent high quality retrievable records were achieved using the preselected task forms, superior to those formed on blank paper. PMID- 1510902 TI - Infantile fibromatosis with involvement of the mandible. AB - Two unusual cases of infantile fibromatosis involving the mandible occurring in 2 year-old children are described. These tumours, though initially highly aggressive, underwent spontaneous regression in the absence of definitive treatment. PMID- 1510903 TI - Obstructive sleep apnoea syndrome presenting as lingual ulceration. AB - Two patients with obstructive sleep apnoea syndrome are reported where the initial presenting complaint was of lingual ulceration. This unusual presentation has not been reported previously. Both patients experienced frequent apnoeic episodes during sleep with a profound fall in the arterial oxygen saturation. It is postulated that the lingual ulceration resulted from repeated trauma to the tongue by the teeth as the patient made violent inspiratory efforts at the termination of an apnoeic episode. The diagnosis of sleep apnoea syndrome was based upon suggestive symptoms of snoring, morning fatigue and day-time somnolence plus a minimum of 15 apnoeic episodes per hour of sleep. The first line investigations of this condition are available in all district general hospitals and a diagnosis of sleep apnoea syndrome obtained. Referral to a regional sleep study centre may be appropriate prior to the commencement of therapy. Management is predominantly medical, consisting of weight loss and the administration of nocturnal nasal continuous positive airways pressure. PMID- 1510904 TI - Liposarcoma of the tongue: a case report and review of the literature. AB - A case of the rare intraoral liposarcoma which presented as a lump on the tongue of 5 years duration is reported. The difficulty of accurate clinical and histopathological diagnosis of this lesion is outlined. PMID- 1510905 TI - Papillary cystadenocarcinoma of the sublingual gland presenting as a ranula. AB - A case is reported of a papillary cystadenocarcinoma of the sublingual gland which presented as a ranula. This is both rare in site and mode of presentation. PMID- 1510906 TI - Sialolithiasis of minor salivary glands. AB - Sialolithiasis of minor salivary glands is generally considered to be extremely rare. Reports of seven cases are presented. A review of the literature suggests that the condition is not as uncommon as previously considered, and that definitive histopathological diagnosis of lip swellings should be obtained due to the incidence of labial pleomorphic adenoma and the possibility of the clinical misdiagnosis with sialolithiasis. PMID- 1510907 TI - A visor attachment for the Royal Berkshire Halo: a simplified method of craniofacial fixation. PMID- 1510908 TI - Recurrent odontogenic keratocyst within the temporalis muscle. PMID- 1510909 TI - Overseas Dentists Training Scheme. PMID- 1510910 TI - Oropharyngeal squamous cell carcinoma presenting as glossopharyngeal neuralgia. PMID- 1510911 TI - Contrast radiography in the management of dysphagia after surgery for oral malignancy. PMID- 1510912 TI - Casualty without maxillofacial surgery--back to the future? PMID- 1510913 TI - Prediction of structural and functional features of protein and nucleic acid sequences by artificial neural networks. AB - The applications of artificial neural networks to the prediction of structural and functional features of protein and nucleic acid sequences are reviewed. A brief introduction to neural networks is given, including a discussion of learning algorithms and sequence encoding. The protein applications mostly involve the prediction of secondary and tertiary structure from sequence. The problems in nucleic acid analysis tackled by neural networks are the prediction of translation initiation sites in Escherichia coli, the recognition of splice junctions in human mRNA, and the prediction of promoter sites in E. coli. The performance of the approach is compared with other current statistical methods. PMID- 1510914 TI - Functional topology of a surface loop shielding the catalytic center in lipoprotein lipase. AB - Lipoprotein lipase (LPL), hepatic lipase, and pancreatic lipase show high sequence homology to one another. The crystal structure of pancreatic lipase suggests that it contains a trypsin-like Asp-His-Ser catalytic triad at the active center, which is shielded by a disulfide bridge-bounded surface loop that must be repositioned before the substrate can gain access to the catalytic residues. By sequence alignment, the homologous catalytic triad in LPL corresponds to Asp156-His241-Ser132, absolutely conserved residues, and the homologous surface loop to residues 217-238, a poorly conserved region. To verify these assignments, we expressed in vitro wild-type LPL and mutant LPLs having single amino acid mutations involving residue Asp156 (to His, Ser, Asn, Ala, Glu, or Gly), His241 (to Asn, Ala, Arg, Gln, or Trp), or Ser132 (to Gly, Ala, Thu, or Asp) individually. All 15 mutant LPLs were totally devoid of enzyme activity, while wild-type LPL and other mutant LPLs containing substitutions in other positions were fully active. We further replaced the 22-residue LPL loop which shields the catalytic center either partially (replacing 6 of 22 residues) or completely with the corresponding hepatic lipase loop. The partial loop replacement chimeric LPL was found to be fully active, and the complete loop replacement mutant had approximately 60% activity, although the primary sequence of the hepatic lipase loop is quite different. In contrast, replacement with the pancreatic lipase loop completely inactivated the enzyme. Our results are consistent with Asp156-His241-Ser132 being the catalytic triad in lipoprotein lipase.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1510915 TI - Denaturation of human Cu/Zn superoxide dismutase by guanidine hydrochloride: a dynamic fluorescence study. AB - The unfolding of holo and apo forms of human Cu/Zn superoxide dismutase by guanidine hydrochloride has been investigated by steady-state and dynamic fluorescence. In agreement with previous observations, a stabilizing effect of the metal ions on the protein tertiary structure was apparent from comparison of apo- and holoproteins, which both showed a sharp sigmoidal transition though at different denaturant concentrations. The transition was also followed by circular dichroism to check the extent of secondary structure present at each denaturant concentration. The results are incompatible with a simple two-state mechanism for denaturation. The occurrence of a more complicated process is supported by the emission decay properties of the single tryptophanyl residue at different denaturant concentrations. A complex decay function, namely, two discrete exponentials or a continuous distribution of lifetimes, was always required to fit the data. In particular, the width of the lifetime distribution, which is maximum at the transition midpoint, reflects heterogeneity of the tryptophan microenvironment and thus the presence of different species along the denaturation pathway. In the unfolded state, the width of the lifetime distribution is broader than in the folded state probably because the tryptophan residue is affected by a larger number of local conformations. The dissociation of the dimer was also studied by varying the protein concentration at different denaturant concentrations. This process affects primarly the surface of the protein rather than its secondary structure as shown by a comparison between the tryptophan emission decay and circular dichroism data under the same conditions. Another consequence of dissociation is a greater instability in the structure of the monomers, which are more easily unfolded.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1510916 TI - Kinetic analysis of folding and unfolding the 56 amino acid IgG-binding domain of streptococcal protein G. AB - The 56 amino acid B domain of protein G (GB) is a stable globular folding unit with no disulfide cross-links. The physical properties of GB offer extraordinary flexibility for evaluating the energetics of the folding reaction. The protein is monomeric and very soluble in both folded and unfolded forms. The folding reaction has been previously examined by differential scanning calorimetry (Alexander et al., 1992) and found to exhibit two-state unfolding behavior over a wide pH range with an unfolding transition near 90 degrees C (GB1) at neutral pH. Here, the kinetics of folding and unfolding two naturally occurring versions of GB have been measured using stopped-flow mixing methods and analyzed according to transition-state theory. GB contains no prolines, and the kinetics of folding and unfolding can be fit to a single, first-order rate constant over the temperature range of 5-35 degrees C. The major thermodynamic changes going from the unfolded state to the transition state are (1) a large decrease in heat capacity (delta Cp), indicating that the transition state is compact and solvent inaccessible relative to the unfolded state; (2) a large loss of entropy; and (3) a small increase in enthalpy. The most surprising feature of the folding of GB compared to that of previously studied proteins is that its folding approximates a rapid diffusion controlled process with little increase in enthalpy going from the unfolded to the transition state. PMID- 1510917 TI - Helix formation in enzymically ligated peptides as a driving force for the synthetic reaction: example of alpha-globin semisynthetic reaction. AB - The alpha-globin semisynthetic reaction, namely, the ligation of the complementary fragments of alpha-globin, alpha 1-30 and alpha 31-141, in the presence of 30% l-propanol that is catalyzed by V8 protease is distinct as compared with the previously studied protease-catalyzed splicing of the discontinuity sites of the fragment complementing systems [Sahni et al. (1989) Biochemistry 28, 5456]. The complementary fragments of alpha-globin do not exhibit noncovalent interaction between them even in the presence of l-propanol, the organic cosolvent used to facilitate the alpha-globin semisynthetic reaction. Besides, a significant portion of the fragment alpha 31-141 does not contribute to the protease-catalyzed splicing reaction. Alpha 1-30 and alpha 31-40 are ligated by V8 protease to yield alpha 1-40 in much the same way as the splicing of alpha 1-30 with either alpha 31-141 or alpha 31-47 to yield alpha-globin or alpha 1-47, respectively. An equimolar mixture of alpha 1-30 and alpha 31-40 does not show any 'complexation' in the presence of 30% l-propanol, the medium used for the synthetic reaction. The splicing junction, i.e., Glu30-Arg31 peptide bond, is located in the middle of the B-helix (residues 20-35) of the parent protein. Most of the residues from the A-helix of the protein could also be deleted from segment alpha 1-30 without influencing the V8 protease-catalyzed splicing reaction.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1510918 TI - Metabolic thermotolerance: magnetic resonance detected protection of glutamate synthase. AB - Metabolism in maize meristem cultures exposed to different heat treatments has been analyzed by 13C-NMR spectroscopy of tissue extracts. The effects of a 40 degrees C permissive stress were compared with a 45 degrees C lethal stress, and the metabolism of glutamate and glutamine were markedly altered by both temperatures. Changes in the incorporation of labeled precursors, alterations due to the in vivo application of enzyme inhibitors, and differences in the activity of enzymes in cell free extracts have confirmed that glutamate synthase (GluS) is partially inactivated by the lethal thermal exposure. This enzyme is quantitatively protected by the induction of thermotolerance. The time dependence for the protection correlates with the appearance of a set of late-arising heat shock proteins (hsps). The function of these late-arising proteins is not yet known, but only one of them, a 67-kDa protein, is spatially correlated with GluS protection. Therefore, the quantitative protection of a key metabolic enzyme has been correlated with the in vivo function of a specific hsp. PMID- 1510919 TI - Crystal structure of chicken liver dihydrofolate reductase complexed with NADP+ and biopterin. AB - The 2.2-A crystal structure of chicken liver dihydrofolate reductase (EC 1.5.1.3, DHFR) has been solved as a ternary complex with NADP+ and biopterin (a poor substrate). The space group and unit cell are isomorphous with the previously reported structure of chicken liver DHFR complexed with NADPH and phenyltriazine [Volz, K. W., Matthews, D. A., Alden, R. A., Freer, S. T., Hansch, C., Kaufman, B. T., & Kraut, J. (1982) J. Biol. Chem. 257, 2528-2536]. The structure contains an ordered water molecule hydrogen-bonded to both hydroxyls of the biopterin dihydroxypropyl group as well as to O4 and N5 of the biopterin pteridine ring. This water molecule, not observed in previously determined DHFR structures, is positioned to complete a proposed route for proton transfer from the side-chain carboxylate of E30 to N5 of the pteridine ring. Protonation of N5 is believed to occur during the reduction of dihydropteridine substrates. The positions of the NADP+ nicotinamide and biopterin pteridine rings are quite similar to the nicotinamide and pteridine ring positions in the Escherichia coli DHFR.NADP+.folate complex [Bystroff, C., Oatley, S. J., & Kraut, J. (1990) Biochemistry 29, 3263-3277], suggesting that the reduction of biopterin and the reduction of folate occur via similar mechanisms, that the binding geometry of the nicotinamide and pteridine rings is conserved between DHFR species, and that the p-aminobenzoylglutamate moiety of folate is not required for correct positioning of the pteridine ring in ground-state ternary complexes. Instead, binding of the p-aminobenzoylglutamate moiety of folate may induce the side chain of residue 31 (tyrosine or phenylalanine) in vertebrate DHFRs to adopt a conformation in which the opening to the pteridine binding site is too narrow to allow the substrate to diffuse away rapidly. A reverse conformational change of residue 31 is proposed to be required for tetrahydrofolate release. PMID- 1510920 TI - Conformation of magainin-2 and related peptides in aqueous solution and membrane environments probed by Fourier transform infrared spectroscopy. AB - The conformational properties of the magainin family of antimicrobial peptides in aqueous solution and in model membranes have been probed by Fourier transform infrared spectroscopy. The magainins were found to be structureless in aqueous solution at neutral pD, confirming other studies by Raman and circular dichroism spectroscopy. Increasing the pD to 10 induced the formation of predominantly alpha-helical secondary structures, with some beta-sheet. In the presence of negatively charged liposomes (dimyristoylphosphatidylglycerol), the peptides folded into alpha-helical secondary structures with some beta-sheet structure evident. On the other hand, in the presence of zwitterionic phospholipids (dimyristoylphosphatidylcholine), the spectra were identical to those in aqueous solution. For some magainins, the interaction with charged liposomes was modulated by the presence of cholesterol; cholesterol was found to promote the formation of beta-sheet structures, as evidenced by the appearance of amide I bands at 1614 and 1637 cm-1. Differences in structure were observed between the amidated and nonamidated forms of some peptides. From the data, a mechanism of antimicrobial action of the magainin family of peptides is proposed. PMID- 1510921 TI - Brominated phospholipids as a tool for monitoring the membrane insertion of colicin A. AB - The intrinsic fluorescence of the colicin A thermolytic fragment does not change after insertion into normal phospholipid vesicles and is thus an unsuitable probe for monitoring the membrane insertion process. In this paper, we report the results of studies on the quenching of this fluorescence by brominated dioleoylphosphatidylglycerol (Br-DOPG) vesicles. Bromine atoms located at the midpoint of the phospholipid acyl chain quench the tryptophan fluorescence, indicating contact between fluorophores of the protein and the bilayer's hydrophobic core. Addition of Br-DOPG vesicles to a protein solution quenches the tryptophan fluorescence in a time-dependent manner. This quenching can be fitted to a single-exponential function, and thus interpreted as a one-step process. This allows calculation of an apparent rate constant of protein insertion into the membrane. Parameters known to affect the insertion of the thermolytic fragment into phospholipid monolayers or vesicles (pH and negative charge density) also affect the rate constant in comparable ways. In addition to the information gained concerning membrane exposure in the steady state, this approach provides the first real-time method for measuring the insertion of colicin into membranes. It is highly quantitative and can be used on all versions of the protein, e.g., full size, proteolytic fragments, and mutants. Brominated lipids provide experimental conditions identical to normal lipids and allow for great flexibility in protein/lipid ratios and concentrations. The kinetic analysis shows clearly the existence of a two-step process involving a rapid adsorption of the protein to the lipid surface followed by a slow insertion. PMID- 1510922 TI - Transient-state kinetic evidence for intersubunit allosteric hysteresis during band 3 anion exchange. AB - On-line, dual-wavelength stopped-flow spectroscopy was used to follow continuously, the uptake of dithionite (S2O4(2-)) into human erythrocyte resealed ghosts. We describe the general characteristics of a pre-steady-state transient phase measured both with chloride and sulfate as co-anions. We then quantitatively characterize the dithionite concentration dependence of the amplitude factor and relaxation constant (kR) for the transient phase measured in sulfate medium. We also study the dithionite dependence of the steady-state velocity. Our results suggest that dithionite induces a slow conformational change in band 3 leading to hysteresis in the transport velocity. As many as 25 turnovers of the transport cycle per monomer can occur prior to attainment of steady state. Both kR and the amplitude factor for the transient phase were dithionite concentration dependent. In addition, the steady-state velocity showed apparent negative cooperativity. To discriminate between monomeric and intersubunit allosteric hysteresis, we performed a series of critical kinetic tests with cells labeled partially with 4,4'-diisothiocyanatostilbene-2,2' disulfonate (DIDS). Coverage of 85% of the band 3 monomer population with DIDS caused kR to decrease about 10-fold, the dithionite concentration dependence of kR to change significantly, and the apparent negative cooperativity for the steady-state velocity to be eliminated. These results suggest that intersubunit allosteric hysteresis makes a significant contribution to dithionite transport by band 3. PMID- 1510923 TI - A heat shock protein complex isolated from rabbit reticulocyte lysate can reconstitute a functional glucocorticoid receptor-Hsp90 complex. AB - When unliganded glucocorticoid receptor that has been stripped free of associated proteins is incubated with rabbit reticulocyte lysate, the receptor becomes associated with the 70- and 90-kDa heat shock proteins (hsp70 and hsp90), and the untransformed state of the receptor is functionally reconstituted [Scherrer, L. C., Dalman, F. C., Massa, E., Meshinchi, S., & Pratt, W. B. (1990) J. Biol. Chem. 265, 21397-21400]. Recently, an hsp70-containing protein complex (200-250 kDa) purified from rabbit reticulocyte lysate was shown to maintain a fusion protein bearing the mitochondrial matrix-targeting signal in a state that is competent for mitochondrial import [Sheffield, W. P., Shore, G. C., & Randall, S. K. (1990) J. Biol. Chem. 265, 11069-11076]. In this work, we show that this partially purified mitochondrial import-competent fraction contains both hsp90 and hsp70. When the purified fraction is immunoadsorbed with a monoclonal antibody specific for hsp90, a significant portion of the hsp70 is co-immunoadsorbed, suggesting that hsp90 and hsp70 are present together as a complex. The partially purified fraction maintains a hybrid precursor protein containing the mitochondrial matrix targeting signal of rat pre-ornithine carbamyl transferase in an import-competent state. Incubation of immunopurified glucocorticoid receptor with this fraction of reticulocyte lysate results in ATP-dependent association of the receptor with both hsp70 and hsp90, and the resulting complexes are functional as assessed by return of the receptor to the high-affinity steroid binding conformation. The glucocorticoid receptor hetero-complex reconstituting activity of the lysate fraction is low relative to its mitochondrial import activity. Importantly, however, this is the first demonstration of the functional and structural reconstitution of the untransformed state of any steroid receptor utilizing a partially purified system. PMID- 1510924 TI - Identification and localization of a cysteinyl residue critical for the trypsin like catalytic activity of the proteasome. AB - Chemical modification of the proteasome with N-ethylmaleimide (NEM) was performed for the purpose of identifying amino acid residues that play a role in the enzyme's proteolytic function. Modification of the proteasome with NEM specifically and irreversibly suppressed one of the three peptidase activities of the enzyme, viz., the "trypsin-like" activity. Leupeptin, a reversible competitive inhibitor of this activity, protected the activity from NEM inactivation, suggesting that NEM modifies a residue in the leupeptin binding site. Comparisons of enzyme samples labeled with [14C]NEM either in the presence or in the absence of leupeptin allowed the identification of a proteasome subunit containing an NEM-modified, leupeptin-protected cysteinyl residue. The leupeptin protection experiments suggest that residues of this subunit contribute to the active site responsible for the proteasome's trypsin-like activity. This subunit was purified by reverse-phase high-performance liquid chromatography. Peptide mapping and N-terminal amino acid sequencing were employed to acquire information about the primary structure of the subunit, including the sequence surrounding the leupeptin-protected cysteinyl residue. The sequencing data suggest that this proteasome subunit is evolutionarily related to other proteasome subunits that have been sequenced, which show no homology to other known proteases. The assignment of a catalytic function to a member of the proteasome family supports the hypothesis that proteasome subunits represent a structurally and possibly mechanistically novel group of proteases. PMID- 1510925 TI - A transition state in pieces: major contributions of entropic effects to ligand binding by adenosine deaminase. AB - Nebularine undergoes hydration at the active site of adenosine deaminase, in a reaction analogous to a partial reaction in the displacement of ammonia from adenosine by water, to generate an inhibitory complex that captures much of the binding affinity expected of an ideal transition-state analogue. Enzyme affinities of several compounds related to nebularine 1,6-hydrate, and to its stable analog 2'-deoxycoformycin, were compared in an effort to identify the structural origins of strong binding. Binding of the stable transition-state analog inhibitor 2'-deoxycoformycin was rendered 9.8 kcal/mol less favorable by removal of substituent ribose, 9.7 kcal/mol less favorable by inversion of the 8 hydroxyl substituent of the diazepine ring, and 10.0 kcal/mol less favorable by removal of atoms 4-6 of the diazepine ring. Binding of the unstable transition state analog nebularine hydrate was rendered at least 9.9 kcal/mol less favorable by removal of the 6-hydroxyl group and 10.2 kcal/mol less favorable by removal of atoms 1-3 of the pyrimidine ring. In each case, the enzyme exhibited only modest affinity (Kd greater than or equal to 10(-2) M) for the "missing piece", indicating that incorporation of 2 binding determinants within a single molecule permits an additional 7-12 kcal/mol of intrinsic binding energy to be manifested as observed binding energy. These results are consistent with earlier indications that adenosine deaminase may use 10.5 kcal/mol of the intrinsic free energy of binding of the two substrates to place them in positions appropriate for reaction at the active site, overcoming the unfavorable entropy change of -35 eu for the equilibrium of 1,6-hydration of purine ribonucleoside and reducing the equilibrium constant for attainment of the transition state in deamination of adenosine. Thus, adenosine deaminase may achieve up to 8 orders of magnitude of its catalytic power by converting the nonenzymatic, bimolecular, hydration reaction to a monomolecular reaction at its active site. Several new 6 substituted 1,6-dihydropurine ribonucleosides, prepared by photoaddition of formate and by low-temperature addition of organolithium reagents to a derivative of purine ribonucleoside, exhibited Ki values of 9-1400 microM against adenosine deaminase, in accord with the active site's considerable tolerance of bulky leaving groups in substrates. Inhibition by one diastereomer of 6-carboxy-1,6 dihydropurine ribonucleoside was found to be time-dependent, progressing from a weakly bound to a more strongly bound complex. PMID- 1510926 TI - Substitution of aspartic acid-80, a residue involved in coordination of magnesium, weakens the GTP binding and strongly enhances the GTPase of the G domain of elongation factor Tu. AB - The functional role of Asp80, a residue involved in the coordination of the Mg(2+).guanine nucleotide complex in elongation factor Tu (EF-Tu), has been investigated by its substitution with Asn in the isolated N-terminal domain (G domain). The G domain D80N is characterized by a strong decrease in binding affinity for GTP and magnesium, whereas the affinity for GDP is unchanged. This effect can be mimicked in wild-type G domain by the addition of EDTA. In contrast to this, EDTA does not essentially influence the selective effects of the mutation on the GTP and GDP binding of G domain D80N, indicating that the action of Asp80 is mainly mediated by the GTP-coordinated magnesium ion. The GTPase activity of the G domain D80N is very unstable, but can be markedly stabilized by the addition of glycerol without essentially modifying the specific effects of the mutation. In the absence of glycerol G domain D80N can express a short-lived GTPase activity. The presence of glycerol transforms this evanescent activity into a linear multiple-round activity that under optimal conditions can be almost 2 orders of magnitude higher than the GTPase of wild-type G domain. This enhanced catalytic activity represents the most striking consequence of the mutation and stresses the key role of Asp80 in the GTPase of EF-Tu.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1510927 TI - A 3,4-dichloroisocoumarin-resistant component of the multicatalytic proteinase complex. AB - The multicatalytic proteinase complex (MPC) exhibits three proteolytic activities designated as trypsin-like, chymotrypsin-like, and peptidylglutamyl-peptide hydrolyzing (PGPHA). Evidence based on inhibitor and specificity studies indicates that each of the three activities is associated with a different component of the complex. Inactivation of the three activities by the serine proteinase inhibitor, 3,4-dichloroisocoumarin (DCI), reveals the presence of an additional DCI-resistant component that cleaves natural peptides including neurotensin, dynorphin, angiotensin II, the oxidized B-chain of insulin, and also proinsulin at a rate greater than that of the native uninhibited complex. Examination of the reaction products of neurotensin (NT) and proinsulin degradation showed cleavage of the Ile12-Leu13 bond in NT and cleavage of the Leu44-Ala45 and Val39-Gly40 bonds within the connecting peptide (C-chain) of bovine proinsulin, suggesting preferential cleavage of bonds on the carboxyl side of branched chain amino acids. Although resistant to inhibition by DCI, the component was sensitive to inhibition by the isocoumarin derivatives, 7-amino-4 chloro-3-[3-(isothioureido)propoxy]isocoumarin and 4-chloro-7-guanidino-3-(2 phenylethoxy)isocoumarin. Degradation of NT was activated by leupeptin, chymostatin, and antipain indicating that binding of these aldehyde inhibitors at one site can stimulate proteolytic activity at a different site of the complex. The DCI-resistant component seems to constitute a major component of the complex active in degradation of natural peptides and proteins. PMID- 1510928 TI - Thylakoids from pea seedlings grown under intermittent light: biochemical and flash-spectrophotometric properties. AB - Thylakoid membranes were isolated from pea seedlings grown under intermittent light (2-min light/118-min dark cycles). These preparations differed from controls (thylakoids from plants grown under 16-h light/8-h dark cycles) in the following respects: 15 times smaller chlorophyll/protein ratio, 10 times greater chlorophyll a/b ratio, absence of light-harvesting chlorophyll a/b binding proteins, and 2-3-fold greater ratio of photosystem II over photosystem I. In addition we found the following: (1) Electrogenic electron transfer around cytochrome b6/f under flashing light was greatly enhanced, probably as a consequence of the greater photosystem II/photosystem I ratio. (2) The rate of proton uptake from the medium at the acceptor side of photosystem II was enhanced, probably by unshielding of the quinone binding domain. (3) The N,N' dicyclohexylcarbodiimide sensitivity of the proton-pumping activity of photosystem II was absent, which was consistent with the attribution of a N,N' dicyclohexylcarbodiimide-induced protonic short circuit to chlorophyll a/b binding proteins. (4) The sensitivity of oxygen evolution under continuous light to variations of pH or the concentration of Ca2+ was altered. Chlorophyll a/b binding proteins serve as light-harvesting antennas. We found in addition that they modulated the activity of water oxidation and, in particular, the proteolytic reactions around photosystem II. PMID- 1510929 TI - Proton release during the four steps of photosynthetic water oxidation: induction of 1:1:1:1 pattern due to lack of chlorophyll a/b binding proteins. AB - In photosynthesis of green plants water is oxidized to dioxygen. This four-step process is accompanied by the release of four protons (per molecule of dioxygen) into the lumen of thylakoids. In dark-adapted thylakoids which are excited with a series of short flashes of light, the extent of proton release oscillates with period four as a function of flash number. Noninteger and pH-dependent proton/electron ratios (e.g., 1.1, 0.25, 1.0, and 1.65 at pH 7) have been attributed to a superposition of two reactions: chemical production of protons and transient electrostatic response of peripheral amino acid side chains. Aiming at the true pattern of proton production, we investigated the relative contribution of peripheral proteins. Thylakoids with and without chlorophyll a/b binding proteins were compared. Thylakoids lacking chlorophyll a/b binding proteins were prepared from pea seedlings grown under intermittent light [Jahns, P., & Junge, W. (1992) Biochemistry (preceding paper in this issue)]. We found no oscillation of proton release in the pH range from 6 to 7.5. These and other results showed that chlorophyll a/b binding proteins, which primarily serve as light-harvesting antennas, modulate proton release by water oxidation. A nonoscillating pattern of proton release, with proton/electron ratios of 1:1:1:1 more closely represents the events in the catalytic center proper. This implies hydrogen abstraction rather than electron abstraction from water during the oxygen-evolving step S3----S0. PMID- 1510930 TI - Oxygen yield and thermoluminescence characteristics of a cyanobacterium lacking the manganese-stabilizing protein of photosystem II. AB - Previous experiments have shown that a Synechocystis sp. PCC 6803 mutant (delta psbO) lacking the extrinsic manganese-stabilizing protein (MSP) exhibits impaired, but significant levels of H2O-splitting activity [Burnap, R., & Sherman, L.A. (1991) Biochemistry 30, 440-446]. [14C]DCMU-binding experiments now show that the number and affinity of DCMU-binding sites (normalized to chlorophyll) are equivalent in delta psbO and the wild type, suggesting equal concentrations of assembled reaction centers. A similar conclusion is reached on the basis of measurements of PSII electron transport (DPC-supported DCPIP reduction) by mutant and wild-type thylakoids. The pattern of flash O2 yield by delta psbO cells measured with a bare platinum electrode exhibits a period four oscillation (with a maximum on the third flash), indicating that the H2O splitting enzyme in delta psbO retains the basic mechanistic features found in normal cells. However, the amplitude of these signals is smaller and more highly damped than those obtained from wild-type cells, suggesting the absence of MSP results in a higher miss probability and/or a reduction in the number of centers competent in oxygen evolution. Analysis of the rise kinetics of the ampermeric signal on the bare platinum electrode indicates that the S3-[S4]-S0 transition is retarded by at least a factor of 5 in the mutant. Thermoluminescence emission peak temperatures indicate that the S2QA-, S2QB-, and S3QB-charge pairs are significantly more stable with respect to recombination in the mutant. The intensities of the thermoluminescence emissions are also significantly reduced in the mutant.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1510931 TI - Hormone-induced dissociation of the androgen receptor-heat-shock protein complex: use of a new monoclonal antibody to distinguish transformed from nontransformed receptors. AB - The hormone-induced transformation process of the androgen receptor in the androgen-responsive human prostatic carcinoma cell line LNCaP was studied. Immunoprecipitation of the nontransformed cytosolic receptor (8S on sucrose gradients) with a specific monoclonal antibody (F39.4.1) resulted in coprecipitation of three heat-shock proteins (hsp90, hsp70, and hsp56). Upon incubation of the cells with the synthetic androgen R1881, the sedimentation value of the receptor complex decreased to an intermediate form of 6S, and an almost complete loss of coprecipitating heat-shock proteins was observed. After a 2-h incubation, the receptor was recovered in considerable part from the nuclear fraction (extraction with high salt; 4.6S form). By use of the bifunctional cross linker dimethyl pimelimidate, dissociation of the 8S complex, but not of the 6S complex, was blocked. A newly developed monoclonal antibody (F52.24.4), directed against the C-terminal part of the DNA-binding domain of the androgen receptor, specifically recognized both the 4.6S and the 6S forms of the receptor but did not react with the nontransformed 8S form. It is concluded that the unoccupied androgen receptor is associated with several heat-shock proteins and that transformation of the receptor to the tight nuclear-binding form is a multistep process that involves the dissociation of heat-shock proteins from the receptor. PMID- 1510932 TI - Reconstitution of functional water channels in liposomes containing purified red cell CHIP28 protein. AB - Water rapidly crosses the plasma membranes of red blood cells (RBCs) and renal tubules through highly specialized channels. CHIP28 is an abundant integral membrane protein in RBCs and renal tubules, and Xenopus laevis oocytes injected with CHIP28 RNA exhibit high osmotic water permeability, Pf [Preston et al. (1992) Science 256, 385-387]. Purified CHIP28 from human RBCs was reconstituted into proteoliposomes in order to establish if CHIP28 is itself the functional unit of water channels and to characterize its physiological behavior. CHIP28 proteoliposomes exhibit Pf which is up to 50-fold above that of control liposomes, but permeability to urea and protons is not increased. Like intact RBC, the Pf of CHIP28 proteoliposomes is reversibly inhibited by mercurial sulfhydryl reagents and exhibits a low Arrhenius activation energy. The magnitude of CHIP28-mediated water flux (11.7 x 10(-14) cm3/s per CHIP28) corresponds to the known Pf of intact RBCs. These results demonstrate that CHIP28 protein functions as a molecular water channel and also indicate that CHIP28 is responsible for most transmembrane water movement in RBCs. PMID- 1510933 TI - Two-dimensional NMR studies of the zinc finger motif: solution structures and dynamics of mutant ZFY domains containing aromatic substitutions in the hydrophobic core. AB - Solution structures of mutant Zn fingers containing aromatic substitutions in the hydrophobic core are determined by 2D-NMR spectroscopy and distance geometry/simulated annealing (DG/SA). The wild-type domain (designated ZFY-6) is derived from the human male-associated protein ZFY and represents a sequence motif (Cys-X2-Cys-X-Ar-X7-Leu-X2-His-X4-His) that differs from the consensus (Cys X2,4-Cys-X3-Phe-X5-Leu-X2-His-X3-His) in the location ("aromatic swap") and diversity (Ar = tyrosine, phenylalanine, or histidine) of the central aromatic residue (underlined). In a given ZFY domain the choice of a particular aromatic residue is invariant among vertebrates, suggesting that alternative "swapped" aromatic residues are functionally inequivalent. 2D-NMR studies of analogues containing tyrosine, phenylalanine, or histidine at the swapped site yield the following results. (i) The three DG/SA structures each retain the beta beta alpha motif and exhibit similar staggered-horizontal packing between the variant aromatic residue and the proximal histidine in the hydrophobic core. (ii) The structures and stabilities of the tyrosine and phenylalanine analogues are essentially identical, differing only by local exposure of polar (Tyr p-OH) or nonpolar (Phe p-H) surfaces. (iii) The dynamic stability of the histidine analogue is reduced as indicated by more rapid protein-deuterium exchange of hydrogen bonds related to secondary structure and amide-sulfur coordination (slowly exchanging amide resonances in D2O) and by more extensive averaging of main-chain dihedral angles (3J alpha NH coupling constants). An aspartic acid in the putative DNA recognition surface, whose configuration is well-defined as a possible helix N-cap in the tyrosine and phenylalanine analogues, exhibits multiple weak main-chain contacts in the NOESY spectrum of the histidine analogue; such NOEs are geometrically inconsistent and so provide complementary evidence for structural fluctuations. (iv) Because the three DG ensembles have similar apparent precision, the finding of reduced dynamic stability in the histidine analogue emphasizes the importance of experiments that directly probe fluctuations at several time scales. Our results provide insight into the design of biological metal-binding sites and the relationship of protein sequence to structure and dynamics. PMID- 1510934 TI - The octamer motif in immunoglobulin genes: extraction of structural constraints from two-dimensional NMR studies. AB - Phase-sensitive two-dimensional nuclear Overhauser enhancement (2D NOE) and double-quantum-filtered correlated (2QF-COSY) spectra were recorded at 500 MHz for the DNA duplex d(CATTTGCATC).d(GATGCAAATG), which contains the octamer element of immunoglobulin genes. Exchangeable and nonexchangeable proton resonances including those of the H5' and H5" protons were assigned. Overall, the decamer duplex adopts a B-type DNA conformation. Scalar coupling constants for the sugar protons were determined by quantitative simulations of 2QF-COSY cross peaks. These couplings are consistent with a two-state dynamic equilibrium between a minor N- and a major S-type conformer for all residues. The pseudorotation phase angle P of the major conformer is in the range 117-135 degrees for nonterminal pyrimidine nucleotides and 153-162 degrees for nonterminal purine nucleotides. Except for the terminal residues, the minor conformer comprises less than 25% of the population. Distance constraints obtained by a complete relaxation matrix analysis of the 2D NOE intensities with the MARDIGRAS algorithm confirm the dependence of the sugar pucker on pyrimidine and purine bases. Averaging by fast local motions has at most small effects on the NOE-derived interproton distances. PMID- 1510935 TI - The 31P NMR visibility of ATP in perfused rat liver remains about 90%, unaffected by changes of metabolic state. AB - The 31P NMR visibility of ATP of the perfused rat liver was tested over a wide range of metabolic conditions, including normoxic and hypoxic perfusions, fructose loads, and various intervals of normothermic ischemia, for both ad libitum fed and 24-h fasted rats. The 31P NMR signal of ATP was compared to the concentration of ATP determined by enzymatic assays on liver biopsies performed at the end of NMR acquisition. In a first series of experiments, the NMR resonance of intracellular ATP was quantitated in absolute terms by applying the 1H NMR water signal as internal reference: during normoxic and hypoxic perfusions, a constant amount of ATP (0.43 +/- 0.19 mM, mean +/- SD), approximately 12% of the cellular ATP, is not detected by NMR. Nevertheless, there is a high correlation (slope = 0.96 +/- 0.09; r2 = 0.93) between the measurements of ATP by 31P NMR spectroscopy and by biochemical analysis. In a second series of experiments, there was a highly significant correlation between the NMR and analytical biochemical measurements of ATP for whole range of metabolic states, i.e., fructose loads (1.0-10 mM) and various intervals of normothermic ischemia (ranging from 2 to 12 min), indicating unchanged ATP visibility. Thus, as opposed to the studies of Murphy et al. [Murphy, E., et al. (1988) Biochemistry 27, 526-528], it is concluded that ATP at 37 degrees C remains almost entirely visible in the perfused rat liver, also during ischemia. PMID- 1510936 TI - Redox-induced conformational changes in myoglobin and hemoglobin: electrochemistry and ultraviolet-visible and Fourier transform infrared difference spectroscopy at surface-modified gold electrodes in an ultra-thin layer spectroelectrochemical cell. AB - Using suitable surface-modified electrodes, we have developed an electrochemical system which allows a reversible heterogeneous electron transfer at high (approximately 5 mM) protein concentrations between the electrode and myoglobin or hemoglobin in an optically transparent thin-layer electrochemical (OTTLE) cell. With this cell, which is transparent from 190 to 10,000 nm, we have been able to obtain electrochemically-induced Fourier-transform infrared (FTIR) difference spectra of both proteins. Clean protein difference spectra between the redox states were obtained because of the absence of redox mediators in the protein solution. The reduced-minus-oxidized difference spectra are characteristic for each protein and arise from redox-sensitive heme modes as well as from polypeptide backbone and amino acid side chain conformational changes concomitant with the redox transition. The amplitudes of the difference bands, however, are small as compared to the total amide I absorbance, and correspond to approximately 1% (4%) of the reduced-minus-oxidized difference absorbance in the Soret region of myoglobin (hemoglobin) and to less than 0.1% of the total amide I absorbance. Some of the bands in the 1560-1490-cm-1 spectral regions could be assigned to side-chain vibrational modes of aromatic amino acids. In the conformationally sensitive spectral region between 1680 and 1630 cm-1, bands could be attributed to peptide C = O modes because of their small (2-5 cm-1) shift in 2H2O. A similar assignment could be achieved for amide II modes because of their strong shift in 2H2O.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1510937 TI - A new infrared electronic transition of the oxidized primary electron donor in bacterial reaction centers: a way to assess resonance interactions between the bacteriochlorophylls. AB - The primary electron donor in the reaction center of purple photosynthetic bacteria consists of a pair of bacteriochlorophylls (PL and PM). The oxidized dimer (P+) is expected to have an absorption band in the mid-IR, whose energy and dipole strength depend in part on the resonance interactions between the two bacteriochlorophylls. A broad absorption band with the predicted properties was found in a previously unexplored region of the spectrum, centered near 2600 cm-1 in reaction centers of Rhodobacter sphaeroides and several other species of bacteria that contain bacteriochlorophyll a, and near 2750 cm-1 in Rhodopseudomonas viridis. The band is not seen in the absorption spectrum of the monomeric bacteriochlorophyll cation in solution, and it is missing or much diminished in the reaction centers of bacterial mutants that have a bacteriopheophytin in place of either PL or PM. With the aid of a relatively simple quantum mechanical model, the measured transition energy and dipole strength of the band can be used to solve for the resonance interaction matrix element that causes an electron to move back and forth between PL and PM, and also for the energy difference between states in which a positive charge is localized on either PL or PM. (The absorption band can be viewed as representing a transition between supermolecular eigenstates that are obtained by mixing these basis states.) The values of the matrix element obtained in this way agree reasonably well with values calculated by using semiempirical atomic resonance integrals and the reaction center crystal structures.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1510938 TI - Proximity relationship between the active site of Escherichia coli RNA polymerase and rifampicin binding domain: a resonance energy-transfer study. AB - Escherichia coli RNA polymerase has two subsites, i and i + 1, for the binding of the first two substrates, and the first phosphodiester bond is formed between them during the initiation of transcription. Various studies have shown earlier that the inhibitor rifampicin has little effect, if any, on the formation of this phosphodiester bond. On an earlier occasion, we measured the distance of the i nucleotide from the rifampicin binding site on RNA polymerase using Forster's energy-transfer mechanism [Kumar & Chatterji (1990) Biochemistry 29,317]. In this paper, the 1-aminonaphthalene-5-sulfonic acid (AmNS) derivative of UTP in the presence of 10 mM MgCl2 was used as an energy donor, and its distance from rifampicin was estimated. The modified nucleotide (gamma-AmNS)-UTP binds to RNA polymerase with a Kd of 3 microM and has one binding site in the presence of Mg(II) ion. Fluorescence titration studies performed with or without an initiator indicated that (gamma-AmNS)-UTP exclusively binds to RNA polymerase at the (i + 1) site in the presence of Mg(II). Rifampicin was found to form a 1:1 complex with RNA polymerase bound to labeled UTP. Rifampicin and (gamma-AmNS)-UTP have a substantial spectral overlap with an energy-transfer efficiency close to 50%. Labeled UTP shows a decrease in its excited-state lifetime when bound to the enzyme; the transfer efficiency calculated from lifetime measurements was found to be lower than that estimated from steady-state spectral analysis. Time resolved emission spectral analysis was carried out to differentiate between the free and bound UTP over the enzyme surface.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1510939 TI - Characterization of tryptophan and coenzyme luminescence in tryptophan synthase from Salmonella typhimurium. AB - Tryptophan synthase from Salmonella typhimurium is a bifunctional alpha 2 beta 2 complex that catalyzes the formation of L-tryptophan. We have characterized over the temperature range from 160 to 293 K the fluorescence and phosphorescence properties of the single tryptophan present at position 177 of the beta-subunit and of the pyridoxal 5'-phosphate bound through a Schiff's base in the beta active site. The comparison between the fluorescence of the pyridoxal phosphate bound either to the protein or to valine free in solution indicates substantial protection for the coenzyme against thermal quenching and a greater intensity of the ketoenamine tautomer band. Trp-177 is highly luminescent, and its proximity to the pyridoxal moiety leads to an over 50% quenching of its fluorescence with both reduced and native coenzyme. The Trp phosphorescence spectrum possesses a narrow, well-defined, 0-0 vibrational band centered at 418.5 nm, a wavelength that indicates strong polar interactions with neighboring charges. The observation of delayed fluorescence in the native complex implies that the excited triplet state is involved in a process of triplet-singlet energy transfer to the ketoenamine tautomer. The rate of energy transfer, heterogeneous in low temperature glasses with rate constants of 2.26 and 0.07 s-1, becomes homogeneous in fluid solutions as the coenzyme tautomer interconversion is likely faster than the phosphorescence decay. In both apo- and holo-alpha 2 beta 2, the phosphorescence from Trp-177 is long-lived even at ambient temperature.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1510940 TI - Conformational changes and subunit communication in tryptophan synthase: effect of substrates and substrate analogs. AB - The transmission of regulatory signals between the alpha- and beta-subunits of the tryptophan synthase alpha 2 beta 2 complex from Salmonella typhimurium has been investigated by monitoring the luminescence properties of the enzyme in the presence and in the absence of the alpha-subunit ligand DL-alpha-glycerol 3 phosphate, the alpha- and beta-subunit substrate indole, and the beta-subunit substrate analog L-histidine. The beta-subunit contains as intrinsic probes Trp 177 and pyridoxal 5'-phosphate, whereas the alpha-subunit has been mutagenized by replacing Ala-129 with a Trp residue. In contrast to the inertness of L histidine, DL-alpha-glycerol 3-phosphate was found (i) to alter the phosphorescence spectrum of Trp-129, (ii) to shift the fluorescence thermal quenching profile of both Trp-177 and coenzyme to higher temperature, (iii) to slow down the triplet decay kinetics of Trp-177 in fluid solution, and (iv) to affect the equilibrium between different conformations of the enzyme. These findings provide direct evidence that DL-alpha-glycerol 3-phosphate binding affects the structure of the alpha-subunit and, in the presence of coenzyme, induces a conformational change in the beta-subunit that leads to a considerably more rigid structure. As opposed to DL-alpha-glycerol 3-phosphate, the shortening of the phosphorescence lifetime upon indole binding suggests that this substrate increases structural fluctuations in the beta-subunit. Implications for the mechanism of the allosteric regulation between alpha- and beta-subunits are discussed. PMID- 1510941 TI - Three-point cross-linking: potential red cell substitutes from the reaction of trimesoyl tris(methyl phosphate) with hemoglobin. AB - The symmetrical trifunctional cross-linking reagent trimesoyl tris(methyl phosphate) (3), reacts selectively with amino groups (beta 1Val and beta 82Lys) in the diphosphoglycerate binding site of human hemoglobin A, producing cross linked tetrameric species in good yield. A major species is triply linked, alpha alpha beta 1(82) greater than B beta 82, where B symbolizes benzene-1,3,5 tricarbonyl. Both this triply linked species and the doubly linked species, alpha alpha beta 1B beta 82, produced from deoxyhemoglobin have a considerably lower oxygen affinity than does native hemoglobin while maintaining a high degree of cooperativity (n50 = 2.4), making them potentially useful as red cell substitutes, in principle delivering twice as much oxygen as whole blood between pO2 = 100 and = 40 Torr. The yield of products indicates that triply and doubly linked species form in parallel so that there are independent routes to each. It is proposed that differences in routes are due to stereoisomerism about the amide bonds which form from reaction of the reagent with the protein. PMID- 1510942 TI - Evidence for the extent of insertion of the active site loop of intact alpha 1 proteinase inhibitor in beta-sheet A. AB - The extent of insertion of beta-strand s4A into sheet A in intact serpin alpha 1 proteinase inhibitor (alpha 1PI has been probed by peptide annealing experiments [Schulze et al. (1990) Eur. J. Biochem. 194, 51-56]. Twelve synthetic peptides of systematically varied length corresponding in sequence to the unprimed (N terminal) side of the active site loop were complexed with alpha 1PI. The complexes were then characterized by circular dichroism spectroscopy and tested for inhibitory activity. Four peptides formed complexes which retained inhibitory activity, one of which was nearly as effective as the native protein. Comparison with the three dimensional structures of cleaved alpha 1PI [Lobermann et al. (1984) J. Mol. Biol. 177, 531-556] and plakalbumin [Wright et al. (1990) J. Mol. Biol. 213, 513-528] supports a model in which alpha 1PI requires the insertion of a single residue, Thr345, into sheet A for activity. PMID- 1510943 TI - Retinol-binding protein is in the molten globule state at low pH. AB - Using far- and near-UV circular dichroism, viscosity, tryptophan fluorescence, NMR spectra, binding of a hydrophobic probe, and microcalorimetry, we have shown that the apo form of human retinol-binding protein (RBP) at neutral pH is in a rigid state with properties similar to those of holo-RBP. On the contrary, at acidic pH apo-RBP is in the molten globule state which has been earlier revealed for a number of proteins under mild denaturing conditions. We have also shown that, at equilibrium, the pH-induced retinol release from holo-RBP parallels denaturation of the apoprotein. These findings are consistent with our hypothesis that the transformation of RBP into the molten globule state is involved in the mechanism whereby retinol is delivered to target cells. In particular, a local acidic pH near the membrane surface of target cells might cause the transition of RBP to the molten globule state as well as the release of retinol. PMID- 1510944 TI - Heparin binding to the urokinase kringle domain. AB - The binding of urokinase to immobilized heparin and dextran sulfate was studied using activity assays of the bound urokinase. The markedly higher binding observed with high M(r) urokinase compared to low M(r) urokinase indicated a role for the amino-terminal fragment (ATF). This was confirmed by the use of inactive truncated urokinase and monoclonal antibodies specific for the ATF in competition assays of urokinase binding. Antibody competition assays suggested a site in the kringle domain, and a synthetic decapeptide Arg-52-Trp-62 from the kringle sequence (kringle numbering convention) was competitive in assays of urokinase binding to dextran sulfate and heparin. Heparin binding to the urokinase kringle was unambiguously demonstrated via 1H NMR spectroscopy at 500 MHz. Effective equilibrium association constants (K(a)*) were determined for the interaction of isolated kringle fragment and low M(r) heparin at pH 7.2. The binding was strong in salt-free 2H2O (K(a)* approximately 57 mM-1) and remained significant in 0.15 M NaCl (K(a)* approximately 12 mM-1), supporting a potential physiological role for the interaction. This is the first demonstration of a function for the kringle domain of urokinase, and it suggests that while the classical kringle structure has specificity for lysine binding, there may also exist a class of kringles with affinity for polyanion binding. PMID- 1510945 TI - Inhibition of T7 RNA polymerase initiation by triple-helical DNA complexes: a model for artificial gene repression. AB - An experimental approach is presented for the creation of an artificial and functional repressor/operator interaction that does not involve polypeptides. This in vitro approach confers oligonucleotide regulation upon a bacteriophage T7 RNA polymerase promoter by introducing an overlapping homopurine operator that can be recognized by oligonucleotide-directed DNA triple-helix formation. Recognition of optimized operator sequences in either of two triple-helix motifs is shown to efficiently inhibit T7 RNA polymerase transcription initiation in both a promoter- and oligonucleotide-specific manner. Inhibition due to triple helices of the pyrimidine motif is pH-dependent, as expected. Inhibition by purine motif triple helices is not pH-dependent and occurs efficiently under optimum T7 RNA polymerase transcription conditions. Repression by triple-helix formation can be observed rapidly after addition of purine motif repressor oligonucleotides, even when polymerase has been given prior access to the promoter. The mechanism of repression is shown to be occlusion of polymerase from the promoter rather than trapping of the polymerase in unproductive preinitiation or initiation complexes. In contrast to their inhibition of T7 RNA polymerase initiation, the triple-helical complexes studied here do not detectably inhibit transcription elongation. PMID- 1510946 TI - Cytosine methylation can induce local distortions in the structure of duplex DNA. AB - Methyl groups at the C5 position of pyrimidines located within oligopurine oligopyrimidine tracts in DNA have been shown previously to modulate curvature generated by those tracts. However, it was not known whether the influence of such methyl groups is consequent to the altered helical structure within the tracts themselves. In the current study, it is demonstrated that methylation of cytosines up to three base pairs away from a (dA)5.(dT)5 tract (A-tract) can still result in alterations of the net curvature of the A-tract-containing DNA, as measured by alterations in electrophoretic mobility. This latter effect depends strongly on both the sequence of the non-A-tract DNA and the positions of the methylated C residues. The current results lend further support to the notion that the biological consequences of cytosine methylation may be effected through local alterations in DNA structure as well as through direct protein-DNA interactions. PMID- 1510947 TI - Characterization of Met-139 as the photolabeled amino acid residue in the steroid binding site of sex hormone binding globulin using delta 6 derivatives of either testosterone or estradiol as unsubstituted photoaffinity labeling reagents. AB - Immunopurified human sex hormone binding globulin (SHBG) was photoinactivated and photolabeled by radioinert and radioactive photoaffinity labeling steroids delta 6-testosterone (delta 6-T) and delta 6-estradiol (delta 6-E2). The maximal levels of specific incorporation of these two reagents were 0.50 and 0.33 mol of label/mol of SHBG, respectively. Covalently labeled SHBG fractions were citraconylated, reduced, carboxymethylated, and cleaved by trypsin. Separation of tryptic digests by reverse-phase liquid chromatography gave single radioactive peaks at the same retention times with both steroid reagents. However, the two labeled peptidic fractions could be distinguished by capillary electrophoresis and immunodetection with anti-steroid antibodies, whereas the covalent attachment of radioactivity was confirmed by thin-layer chromatography on silica gel. Edman degradation of the two labeled peptides showed a single sequence His-Pro-Ile ([3H]X)-Arg corresponding to the pentapeptide His-Pro-Ile-Met-Arg 136-140 of SHBG sequence. The coincidence, in both cases, of the absence of an identifiable amino acid residue and of the elution of the most intense peak of radioactivity at the fourth cycle of Edman degradation suggests that the same Met-139 residue was labeled by delta 6-[1,2-3H2]T or by delta 6-[17 alpha-3H]E2. Liquid secondary ion mass spectrometry of the two peptides showed [M+H]+ ions at m/z 939.8 or 923.8, corresponding respectively to the addition of delta 6-T or delta 6-E2 to the pentapeptide. The presence of the steroid molecule in the delta 6-[3H]T pentapeptide conjugate was confirmed by the difference of 2 mass units with the [M+H]+ peak of the delta 6-[4-14C]T-pentapeptide conjugate. PMID- 1510948 TI - G1401: a keystone nucleotide at the decoding site of Escherichia coli 30S ribosomes. AB - 16S ribosomal RNA contains three highly conserved single-stranded regions. Centrally located in one of these regions is the C1400 residue. Zero-length cross linking of this residue to the anticodon of ribosome-bound tRNA showed that it was at or near the ribosomal decoding site [Ehresmann, C., Ehresmann, B., Millon, R., Ebel, J-P., Nurse, K., & Ofengand, J. (1984) Biochemistry 23, 429-437]. To assess the functional significance of sequence conservation of rRNA in the vicinity of this functionally important site, a series of site-directed mutations in this region were constructed and the effects of these mutations on the partial reactions of protein synthesis determined. Mutation of C1400 or C1402 to any other base only moderately affected a set of in vitro protein synthesis partial reactions. However, any base change from the normal G1401 residue blocked all of the tested ribosomal functions. This was also true for the deletion of G1401. Deletion of C1400 or C1402 had more complex effects. Whereas subunit association was hardly affected, 30S initiation complex formation was blocked by deletion of C1400 but much less so by deletion of C1402. Alternatively, tRNA binding to the ribosomal A site was more strongly affected by deletion of C1402 than by deletion of C1400. P site binding was inhibited by either deletion. HPLC analysis of the in vitro reconstituted mutant ribosomes showed that none of the functional effects were due to the absence or gross reduction in amount of any ribosomal protein.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1510949 TI - Observation of pheophytin reduction in photosystem two reaction centers using femtosecond transient absorption spectroscopy. AB - Photosystem two reaction centers have been studied using a sensitive femtosecond transient absorption spectrometer. Measurements were performed at 295 K using different excitation wavelengths and excitation intensities which are shown to avoid multiphoton absorption by the reaction centers. Analyses of results collected over a range of time scales and probe wavelengths allowed the resolution of two exponential components in addition to those previously reported [Durrant, J. R., Hastings, G., Hong, Q., Barber, J., Porter, G., & Klug, D. R. (1992) Chem. Phys. Lett. 188, 54-60], plus the long-lived radical pair itself. A 21-ps component was observed. The process(es) responsible for this component was (were) found to produce bleaching of a pheophytin ground-state absorption band at 545 nm and the simultaneous appearance of a pheophytin anion absorption band at 460 nm resulting in a transient spectrum which was that of the radical pair P680+Ph-. This component is assigned to the production of reduced pheophytin. A lower limit of 60% of the final pheophytin reduction was found to occur at this rate. Despite subtle differences in transient spectra, the lifetime and yield of this pheophytin reduction are essentially independent of excitation wavelength within the signal to noise limitations of these experiments. A long-lived species was also observed. This species is produced by those processes which result in the 21-ps component, and it has a spectrum which is found to be independent of excitation wavelength. This spectrum is characteristic of the primary radical pair state P680+Ph-. In addition, a 200-ps component was found which is tentatively assigned to a slow energy-transfer/trapping process. This component was absent if P680 was excited directly and is therefore not integral to primary radical pair formation. Overall, it is concluded that the rate of pheophytin reduction is limited to (21 ps)-1, even when P680 is directly excited. PMID- 1510950 TI - Structural and functional modulation of the manganese cluster in Ca(2+)-depleted photosystem II induced by binding of the 24-kilodalton extrinsic protein. AB - Depletion of functional Ca2+ from photosystem (PS) II membranes impairs O2 evolution. Redox properties of the Mn cluster as probed by thermoluminescence were modified differently in Ca(2+)-depleted PSII depending on the procedure for Ca2+ extraction. Ca2+ depletion by low-pH treatment gave rise to an abnormally modified S2 state exhibiting a thermoluminescence band with elevated peak temperature accompanied by a marked upshift in threshold temperature for its formation, whereas Ca2+ depletion by NaCl washing in the light followed by the addition of EDTA could generate a similarly modified S2 state only when the Ca(2+)-depleted PSII was reconstituted with the 24-kDa extrinsic proteins. These results indicated that manifestation of the abnormal properties of the Ca(2+) depleted S2 state is significantly contributed by the association of the 24-kDa extrinsic protein to PSII. It was inferred that the 24-kDa extrinsic protein regulates the structure and function of the Mn cluster in the absence of functional Ca2+ through a conformational modulation of the intrinsic protein(s) that bind(s) both Mn and Ca. Features of the extrinsic protein-dependent modulation of the Mn cluster were discussed in relation to the function of Ca2+ in O2 evolution. PMID- 1510951 TI - Structure and dynamics of the dilauroylphosphatidylethanolamine lipid bilayer. AB - A 200-ps molecular dynamics (MD) simulation trajectory of a model dilauroylphosphatidylethanolamine (DLPE) bilayer in water at 315 K has been generated. Segmental order parameters, electron density profiles, and water pair distribution functions have been calculated. Comparison to experiment is made where possible. The dynamics of the system has been studied by analyzing the velocity autocorrelation functions (VAF) of both water and lipid atoms. Furthermore, the diffusive properties of water have been analyzed by computing the mean square displacement (MSD) and orientational correlation function (OCF) of water in two regions around the bilayer. The calculated order parameters show a behavior similar to the liquid crystalline phase of other bilayers, but the region around C1-C3 does not show the expected behavior. The electron density profile shows features that are characteristic of the liquid crystalline phase. The radial distribution functions suggest ordering of water near the charged head groups, which results in about 15 water molecules solvating each lipid molecule. We find from the VAF, MSD, and OCF calculation that the water molecules near the head groups of the lipid bilayer move more slowly than those further away. The VAF of the hydrocarbon chains have features of low-frequency motions that are probably cooperative nature in addition to the high-frequency motions associated with bond angle and torsional motions. PMID- 1510952 TI - Probing actin and liposome interaction of talin and talin-vinculin complexes: a kinetic, thermodynamic and lipid labeling study. AB - Talin purified from human platelets and chicken gizzard smooth muscle is an actin and lipid binding protein. Here, we have investigated the effect of vinculin on (a) talin-nucleated actin polymerization and (b) insertion of talin into lipid bilayers. Calorimetric data show ternary complex formation between talin, vinculin, and actin. Actin-talin, actin-vinculin and actin-(talin-vinculin) binding and rate constants as well as actin polymerization rates for all three protein species have been determined by steady state titration, stopped-flow, and fluorescence assay. In contrast to an increase of the polymerization rate by a factor of less than 2 for actin-talin and actin-(talin-vinculin) when lowering the temperature, we measured a decrease in rates for actin alone and actin vinculin. The overall equilibrium constants (Keq) in the van't Hoff plot proved linear and were of one-step reactions. Thermodynamic data exhibited signs of van der Waal's binding forces. Using the photoactivatable lipid analogue [3H]PTPC/11, which selectively labels membrane-embedded hydrophobic domains of proteins, we also show that talin partially inserts into the hydrophobic bilayer of liposomes. This insertion occurs in a similar manner irrespective of preincubation with vinculin. PMID- 1510953 TI - Polarity of lipid bilayers. A fluorescence investigation. AB - Through steady-state and time-resolved fluorescence experiments, the polarity of the bilayers of egg phosphatidylcholine vesicles was studied by means of the solvatochromic 2-anthroyl fluorophore which we have recently introduced for investigating the environmental micropolarity of membranes and which was incorporated synthetically in phosphatidylcholine molecules (anthroyl-PC) in the form of 8-(2-anthroyl)octanoic acid. Fluorescence quenching experiments carried out with N,N-dimethylaniline and 12-doxylstearic acid as quenchers showed that the 2-anthroyl chromophore was located in depth in the hydrophobic region of the lipid bilayer corresponding to the C9-C16 segment of the acyl chains. Steady state fluorescence spectroscopy revealed a nonstructured and red-shifted (lambda em(max) = 464 nm) spectrum for the probe in egg-PC bilayers, which greatly differed from the structured and blue (lambda em(max) = 404 nm) spectrum the fluorophore was shown to display in n-hexane. While the fluorescence decays of the fluorophore in organic solvents were monoexponential, three exponentials were required to account for the fluorescence decays of anthroyl-PC in egg-PC vesicles, with average characteristic times of 1.5 ns, 5.5 ns, and 20 ns. These lifetime values were independent of the emission wavelength used. Addition of cholesterol to the lipid did not alter these tau values. One just observed an increase in the fractional population of the 1.5-ns short-living species detrimental to the population of the 20-ns long-living ones. These observations enabled time-resolved fluorescence spectroscopy measurements to be achieved in the case of the 1/1 (mol/mol) egg-PC/cholesterol mixture. Three distinct decay associated spectra (DAS) were recorded, with maximum emission wavelengths, respectively, of 410 nm, 440 nm, and 477 nm for the 1.5-ns, 6-ns, and 20-ns lifetimes found in this system. On account of the properties and the polarity scale previously established for the 2-anthroyl chromophore in organic solvents, these data strongly suggest the occurrence of three distinct excited states for anthroyl-PC in egg-PC bilayers, corresponding to three environments for the 2 anthroyl chromophore, differing in polarity. The lifetime of 1.5 ns and the corresponding structured and blue (lambda em(max) = 410 nm) DAS account for a hydrophobic environment, with an apparent dielectric constant of 2, which is that expected for the hydrophobic core of the lipid bilayer.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1510954 TI - Effect of diacylglycerols on the activity of cobra venom, bee venom, and pig pancreatic phospholipases A2. AB - The effects of a series of diacylglycerols (DAGs) with varying acyl chain lengths and degree of unsaturation on the activity of cobra venom, bee venom, and pig pancreatic phospholipases A2 (PL-A2S) were studied using two lipid substrates: dipalmitoylphosphatidylcholine (DPPC) or bovine liver phosphatidylcholine (BL PC). The activities of the phospholipases critically depended on the chain length and degree of unsaturation of the added DAGs and on the chemical composition of the substrate. The effects of DAGs on cobra or bee venom PL-A2S were similar, but significantly different from the pig pancreatic PL-A2. The data, taken together with our previous NMR studies on physicochemical effects of these DAGs on lipid bilayer structure [De Boeck, H., & Zidovetzki, R. (1989) Biochemistry 28, 7439; (1992) Biochemistry 31, 623], allowed detailed correlation of the type of a bilayer perturbation induced by DAG with the activation or inhibition of the phospholipase on the same system. In general, the activation of the phospholipases correlated with the DAG-induced defects of the lipid bilayer structure. The results, however, argue against general designation of DAGs as "activators" or "inhibitors" of PL-A2S. Thus, for example, diolein activated phospholipases with the BL-PC lipid substrate, but inhibited them with the DPPC substrate. Dihexanoylglycerol and dioctanoylglycerol inhibited pig pancreatic PL A2 with both lipid substrates and inhibited cobra or been venom PL-A2 with the DPPC substrate, but activated the latter two enzymes with the BL-PC substrate. Longer-chain DAGs (C greater than 12), which induce lateral phase separation of the bilayers into the regions of different fluidities, activated all PL-A2S with both lipid substrates.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1510955 TI - Effect of lipid hydroperoxide on lipoxygenase kinetics. AB - In order to investigate the activation of lipoxygenase and to clarify the role of the oxygenation product hydroperoxide in this process, the effect of 13 hydroperoxylinoleic acid (P, 0-35 microM) on linoleic acid (S, 1-80 microM) oxygenation catalysis by 12 nM lipoxygenase-1 from soybean was studied at pH 10, 25 degrees C, and 240 microM O2 with rapid kinetic techniques. The following observations were made: (1) Iron(II) and iron(III) lipoxygenases are kinetically different: reactions started with the Fe(II) enzyme form show a lag phase, whereas iron(III) lipoxygenase induces an initial burst. (2) Oxidation of the enzyme alone is not sufficient to abolish the lag phase: at [S] greater than 50 microM, the initial burst in the iron(III) lipoxygenase curves is still followed by a lag. The lag phase disappears completely only in the presence of micromolar quantities of P. (3) The approximate dissociation constants for S and P are 15 and 24 microM, respectively, 1 order of magnitude smaller than the corresponding values in the absence of oxygen. The observed kinetics are predicted by numerical integration of the rate equations of a model based on the single lipid binding site mechanism for the anaerobic lipoxygenase reaction [Ludwig et al. (1987) Eur. J. Biochem. 168, 325-337; Verhagen et al. (1978) Biochim. Biophys. Acta 529, 369 379]. A quasi-steady-state approximation of the model suggests that a high [S]/[P] the fraction of active iron(III) lipoxygenase is small and that, therefore, a lag phase is intrinsic to the mechanism. PMID- 1510956 TI - High-affinity Ca(2+)- and substrate-binding sites on protein kinase C alpha as determined by nuclear magnetic resonance spectroscopy. AB - Water proton nuclear magnetic resonance (NMR) relaxation rates were used to identify metal sites on protein kinase C (PKC) isozymes alpha and beta using paramagnetic Gd3+ as a probe. The paramagnetic effect of Gd3+ on water proton relaxation was enhanced with PKC isozymes alpha and beta in the presence of diheptanoylphosphatidylcholine/1,2-dioleoyl-sn-glycerol (PC7/DO). The data are consistent with a single class of metal-binding sites on PKC beta and two classes of sites on PKC alpha: a single high-affinity site with a KD for Gd3+ of 0.2 microM and a larger class of sites with a lower affinity for Gd3+. Titration with Ca2+ abolished the observed enhancement of water proton relaxation by the PKC alpha.Gd3+ complex, consistent with displacement of Gd3+ by Ca2+. Titrations of the PKC alpha.Gd3+ complex with Co(NH3)4ATP, a substitution-inert analogue of ATP, caused a substantial decrease in the observed water proton relaxation enhancement, consistent with formation of a ternary enzyme.metal.substrate complex with a KPKC alpha.Gd.[CoATP] of 30-100 nM. Titration of the metal enzyme complex with a model peptide substrate derived from the pseudosubstrate sequence of PKC alpha caused a similar decrease in enhancement at stoichiometric concentrations consistent with the formation of a PKC alpha.Gd3+.peptide complex with a KPKC alpha.Gd.[peptide] of less than or equal to 13 nM. Titrations of the fully formed PKC alpha.Gd3+.peptide complex with Co(NH3)4ATP caused a further decrease in enhancement consistent with formation of a quaternary complex.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1510957 TI - Dioxygen transfer during vitamin K dependent carboxylase catalysis. AB - The vitamin K dependent carboxylase of liver microsomes is involved in the posttranslational modification of certain serine protease zymogens which are critical components of the blood clotting cascade. During coupled carboxylation/oxygenation this carboxylase converts glutamate residues, dihydrovitamin K, CO2, and O2 to a gamma-carboxyglutamyl (Gla) residue, vitamin K (2R,3S)-epoxide, and H2O with a stoichiometry of 1:1 for all substrates and products. In this paper we investigate the role of molecular oxygen in the reaction by following the course of the oxygen atoms using 18O2. Two different mass spectroscopic techniques, electron ionization positive ion mass spectrometry and supercritical fluid chromatography-negative ion chemical ionization mass spectrometry, were used to quantitate the amount of 18O incorporation into the various oxygens of the vitamin K epoxide product. We found that 0.95 mol atoms of oxygen were incorporated into the epoxide oxygen, 0.05 mol atoms of oxygen were incorporated into the quinone oxygen of vitamin K epoxide, and the remaining ca. 1.0 mol atoms of oxygen were incorporated into H2O. No incorporation of oxygen into vitamin K epoxide from 50% H2(18)O was observed. Thus, the carboxylase operates as a dioxygenase 5% of the time during carboxylation/oxygenation. The relevance of these findings with respect to the nonenzymic "basicity enhancement" model proposed by Ham and Dowd [(1990) J. Am. Chem. Soc. 112, 1660-1661] is discussed. PMID- 1510958 TI - Unusual secondary specificity of prolyl oligopeptidase and the different reactivities of its two forms toward charged substrates. AB - Prolyl oligopeptidase belongs to a new family of serine proteases which contains both exo- and endopeptidases, and this suggests that the enzyme binds its substrate in a special manner. Its secondary specificity, i.e., its interaction with the other residues linked to the proline that accounts for the primary specificity, has been investigated by using peptide substrates of various length and charge. Elongation of the classic dipeptide substrate Z-Gly-Pro-2 naphthylamide with 1-3 residues (Gln, Ala-Gln, Ala-Ala-Gln, and Ala-Lys-Gln) resulted in decreased specificity rate constants. This indicated a limited binding site for prolyl oligopeptidase, a major difference from the finding with other serine endopeptidases. Insertion of charged residues into the substrates, such as lysine or aspartic acid, considerably affected the rates and the pH-rate profiles. The rate constants were higher with the positively charged peptides and lower with the substrates bearing a negative charge. These electrostatic effects were reduced at high ionic strength. The results can be interpreted in terms of a negatively charged active site, which exists at high pH and exerts electrostatic attraction or repulsion toward charged substrates. The pH dependencies of the rate constants with neutral substrates exhibited roughly bell-shaped curves, whereas with charged substrates the existence of two active enzyme forms was clearly demonstrated. The physiologically competent high pH form preferred positively charged substrates (Z-Lys-Pro-2-(4-methoxy)naphthylamide, Z-Ala-Lys Gln-Gly-Pro-2-naphthylamide), whereas the low pH form reacted faster with the negatively charged substrate (Z-Asp-Gly-Pro-2-naphthylamide).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1510959 TI - Pertussis toxin-catalyzed ADP-ribosylation of G(o) alpha with mutations at the carboxyl terminus. AB - The guanine nucleotide-binding protein G(o alpha) has been implicated in the regulation of Ca2+ channels in neural tissues. Covalent modification of G(o alpha) by pertussis toxin-catalyzed ADP-ribosylation of a cysteine (position 351) four amino acids from the carboxyl terminus decouples G(o alpha) from receptor. To define the structural requirements for ADP-ribosylation, preparations of recombinant G(o alpha) with mutations within the five amino acids at the carboxyl terminus were evaluated for their ability to serve as pertussis toxin substrates. As expected, the mutant in which cysteine 351 was replaced by glycine (C351G) was not a toxin substrate. Other inactive mutants were G352D and L353 delta/Y354 delta. Mutations that had no significant effect on toxin-catalyzed ADP ribosylation included G350D, G350R, Y354 delta, and L353V/Y354 delta. Less active mutants were L353G/Y354 delta, L353A/Y354 delta, and L353G. ADP-ribosylation of the active mutants, like that of wild-type G(o alpha), was enhanced by the beta gamma subunits of bovine transducin. It appears that three of the four terminal amino acids critically influence pertussis toxin-catalyzed ADP-ribosylation of G(o alpha). PMID- 1510960 TI - Secondary structure of human interleukin 2 from 3D heteronuclear NMR experiments. AB - Recombinant 15N-labeled human interleukin 2 (IL-2) has been studied by 2D and 3D NMR using uniformly 15N-labeled protein. Assignment of the backbone resonances has enabled the secondary structure of the protein to be defined. The secondary structure was found to consist of four alpha-helical regions and a short section of antiparallel beta-sheet. This structure is more similar to recent published structures of interleukin 4 and granulocyte-macrophage colony-stimulating factor than to a structure of IL-2 previously obtained from low-resolution X-ray diffraction data. PMID- 1510961 TI - Simulation of the thermal denaturation of hen egg white lysozyme: trapping the molten globule state. AB - In the study of protein folding, much attention has focused on the characterization of folding intermediates. We report here molecular dynamics simulations in which the initial stages of the thermal denaturation of hen egg white lysozyme in aqueous solution are examined in detail. It is found that lysozyme unfolds in a two-stage process with the initial formation a quasi-stable state in which significant rearrangement of the secondary structure takes place. No evidence for distinct folding domains was found. The simulations suggest that the formation of well-defined secondary structure occurs after the initial collapse of the peptide chain and thus tend against the framework model of protein folding. PMID- 1510962 TI - Protein folding: assignment of the energetic changes of reversible chemical modifications to the folded or unfolded states. AB - Reversible chemical modifications of a series of single cysteine-containing variants of T4 lysozyme combined with thermal denaturation studies have been used to study the effects of these modifications on the stability of the protein. This allows dissection of the energetic effects of the modification on both the native and denatured states of this protein. At some sites modifications with various chemical reagents have essentially no effect on the stability of the protein, while at others, substantial changes in stability are observed. For example, chemical modification of cysteine at site 146 by cystamine (+NH3CH2CH2SSCH2 CH2NH3+) to form the mixed disulfide lowers the stability of the protein by about 1.1 kcal/mol. The reduction in the free energy of folding caused by the chemical modification is attributed to the destabilization of native state (0.9 kcal/mol), with only a relatively small effect from stabilization of the denatured state (0.2 kcal/mol). Chemical modifications of T4 lysozyme at site 146 with various chemical reagents show that the stability of the protein is lowered by a positively charged group and is relatively independent of the size of the side chains. This approach allows the investigation of the thermodynamic consequences of the reversible insertion of a wide variety of chemical entities at specific sites in proteins and, most importantly, allows dissection of the contribution of the chemical modifications to both the folded and unfolding states. It can be applied to almost any suitable macromolecular system. PMID- 1510963 TI - High-resolution NMR study of the pressure-induced unfolding of lysozyme. AB - The pressure-induced reversible unfolding of lysozyme was investigated by high resolution proton magnetic resonance spectroscopy by following the proton spectra of the following residues: His-15 epsilon 1, Trp-28 epsilon 3, Leu-17 delta 2, Cys-64 alpha, and Trp-108 epsilon 3. The experiments were performed at pH 3.9 and 68.5 degrees C in the pressure range from 1 bar to 5 kbar both in the absence and presence of tri-N-acetylglucosamine (tri-NAG). From the pressure-induced changes of the equilibrium between the native and denatured forms of lysozyme, the reaction volumes (delta V) were calculated for each residue. Small but statistically significant differences in delta V were found for residues located in different regions of the protein. For example, delta V for the disulfide bonded Cys-64 alpha is smaller than the delta V's found for the other residues. In particular, the effect of tri-NAG binding to lysozyme was a change of delta V from -10.3 +/- 0.6 cm3/mol to -18.1 +/- 1.7 cm3/mol for the Trp-108 epsilon 3 residue which is located close to the active site. It is important to note that the Cys-64 alpha residue also senses the binding of the substrate analog. The ability to detect statistically significant differences for delta V of individual residues located in different regions of lysozyme represents the main result of these experiments. PMID- 1510964 TI - Circular dichroism studies on calcium binding to two series of Ca2+ binding site mutants of Drosophila melanogaster calmodulin. AB - The Ca(2+)-induced structural changes in mutant calmodulins from Drosophila melanogaster have been studied by circular dichroism. The proteins comprise eight site-specific mutants, in which a bidentate glutamic acid (at position 12 in each Ca2+ binding loop) is replaced with either glutamine (BQ series) or lysine (BK series). Previous studies of these proteins indicate that Ca2+ binding at the mutated site is effectively eliminated by each of these substitutions, with additional effects at nonmutated sites. Circular dichroism has now been used to assess Ca(2+)-induced changes in secondary and tertiary structure in these proteins. In the absence of Ca2+, the helical content of these mutant calmodulins is close to that of the wild-type protein. In excess Ca2+, calmodulins with a mutation in the N-terminal sites show Ca(2+)-induced increases in helicity (CD at 222 nm) that are similar to those of the wild-type protein. In contrast, much less additional helix is induced by Ca2+ in calmodulins with mutations in the C terminal sites, with the two mutations to site IV showing a particularly poor response. Ca(2+)-induced changes to the environment of the single tyrosine of Drosophila calmodulin (Tyr-138 in site IV of the C-terminal domain) have been monitored via CD at 280 nm. The signal from this residue is significantly altered in the Ca(2+)-free form of almost all these mutants, including those in the N terminal domain. This indicates significant interaction between the N- and C terminal domains of these mutants.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1510965 TI - Evidence for temperature-dependent conformational changes in the L-lactate dehydrogenase from Bacillus stearothermophilus. AB - L-Lactate dehydrogenase from Bacillus stearothermophilus (BSLDH) has been shown to change its conformation in a temperature-dependent manner in the temperature range between 25 and 70 degrees C. To provide a more detailed understanding of this reversible structural reorganization of the tetrameric form of BSLDH, we have determined in the presence of 5 mM fructose, 1,6-bisphosphate (FBP) the effect of temperature on far-UV and near-UV circular dichroism (CD), Nile red binding to the enzyme surface, NADH binding, fluorescence polarization of fluorescamine-labeled protein, and hydrogen-deuterium exchange. In addition, we have analyzed the temperature dependence of the dimer-tetramer equilibrium of this protein by steady-state enzyme kinetics in the absence of FBP. The results obtained from these measurements at various temperatures can be summarized as follows. No changes in the secondary-structure distribution are detectable from far-UV CD measurements. On the other hand, near-UV CD data reveal that changes in the arrangements of aromatic side chains do occur. With increasing temperature, the asymmetry of the environment around aromatic residues decreases with a small change at 45 degrees C and a more pronounced change at 65 degrees C. Nile red binding data suggest that the BSLDH surface hydrophobicity changes with temperature. It appears that decreasing the surface hydrophobicity may be a strategy to increase the protein stability of the active enzyme. We have noted significant alterations in the thermodynamic binding parameters of NADH above 45 degrees C, indicating a conformational change in the active site at 45 degrees C. The hydrodynamic volume of BSLDH is also temperature dependent.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1510966 TI - Incorporation of a stabilizing Ca(2+)-binding loop into subtilisin BPN'. AB - A rational approach was taken to improve the stability of subtilisin BPN' to autoproteolysis. Two sites of autoproteolysis were identified by isolation of early autolysis products and amino-terminal sequence analysis. These studies showed that subtilisin rapidly cleaves Ala48-Ser49 and Ser163-Thr164 peptide bonds at elevated temperatures. These two sites appear in regions of high mobility as estimated from crystallographic B-factors and are in extended surface loops. To improve the resistance to thermal-induced autolysis, we replaced sequences around these two sites with sequences derived from a thermophilic homologue of subtilisin, thermitase. Thermitase contains a Ca(2+)-binding site in the region surrounding Ser49. When the Ca(2+)-binding segment of thermitase corresponding to residues 45-63 of subtilisin BPN' was installed into subtilisin BPN', the chimeric protein gained the ability to bind another Ca2+ with moderate affinity (Kd approximately 100 microM). This enzyme had the same kcat as wild type, had a KM value 8-fold larger than wild-type, and was slightly less stable to thermal inactivation in EDTA. However, in 10 mM CaCl2, the mutant subtilisin BPN' was 10-fold more stable to irreversible inactivation at 60 degrees C than wild-type subtilisin BPN' as measured by residual activity against the substrate sAAPF-pna. Next, mutations and deletions derived from thermitase were introduced near the second autolysis loop in subtilisin BPN' (residues 158-165). However, all of these mutants were less stable than wild-type subtilisin. Thus, some (but not all) mutations derived from a thermophilic homologue near sites of autolysis can be stabilizing to a mesophilic protease. PMID- 1510967 TI - Importance of lysine-286 at the NADP site of glutamate dehydrogenase from Salmonella typhimurium. AB - Affinity labeling studies of NADP(+)-glutamate dehydrogenase from Salmonella typhimurium have shown that the peptide Leu-282-Lys-286 is located near the coenzyme site [Haeffner-Gormley et al. (1991) J. Biol. Chem. 266, 5388-5394]. The present study was undertaken to evaluate the role of lysine-286. The mutant enzymes K286R, K286Q, and K286E were prepared by site-directed mutagenesis, expressed in Escherichia coli, and purified. The Vmax values (micromoles of NADPH per minute per milligram of protein) were similar for WT (270), K286R (529), K296Q (409), and K286E (382) enzymes. As measured at pH 7.9, the Km value for NADPH was much greater for K286E (280 microM) than for WT (9.8 microM), K286R (30 microM), or K286Q (66 microM) enzymes. The efficiencies (kcat/Km) of the WT and K286R mutant were similar (1.2 x 10(3) min-1 microM-1 and 1.0 x 10(3) min-1 microM-1, respectively) while those of K286Q (0.30 x 10(3) min-1 microM-1) and K286E (0.07 x 10(3) min-1 microM-1) were greatly reduced. The decreased efficiency of the K286E mutant results from the increase in Km-NADPH, consistent with a role for a basic residue at position 286 which enhances the binding of NADPH. Plots of Vmax vs pH showed the pH optima to be 8.1-8.3 for all enzymes at saturating NADPH concentrations. A 40-fold increase in Km-NADPH for K286E was observed as the pH increased from 5.98 to 8.08, from which a unique pKe of 6.5 was calculated.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1510968 TI - Functional role of a mobile loop of Escherichia coli dihydrofolate reductase in transition-state stabilization. AB - The function of a highly mobile loop in Escherichia coli dihydrofolate reductase was studied by constructing a mutant (DL1) using cassette mutagenesis that had four residues deleted in the middle section of the loop (Met16-Ala19) and a glycine inserted to seal the gap. This part of the loop involves residues 16-20 and is disordered in the X-ray crystal structures of the apoprotein and the NADP+ binary complex but forms a hairpin turn that folds over the nicotinamide moiety of NADP+ and the pteridine moiety of folate in the ternary complex [Bystroff, C., & Kraut, J. (1991) Biochemistry 30, 2227-2239]. The steady-state and pre-steady state kinetics and two-dimensional 1H NMR spectra were analyzed and compared to the wild-type protein. The kinetics on the DL1 mutant enzyme show that the KM value for NADPH (5.3 microM), the KM for dihydrofolate (2 microM), the rate constant for the release of the product tetrahydrofolate (10.3 s-1), and the intrinsic pKa value (6.2) are similar to those exhibited by the wild-type enzyme. However, the hydride-transfer rate declines markedly from the wild-type value of 950 s-1 to 1.7 s-1 for the DL1 mutant and when taken with data for substrate binding indicates that the loop contributes to substrate flux by a factor of 3.5 x 10(4). Thus, the mobility of loop I may provide a mechanism of recruiting hydrophobic residues which can properly align the nicotinamide and pteridine rings for the hydride-transfer process (a form of transition-state stabilization).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1510969 TI - Complementary perturbation of the kinetic mechanism and catalytic effectiveness of dihydrofolate reductase by side-chain interchange. AB - The variable residue Leu-28 of Escherichia coli dihydrofolate reductase (DHFR) and the corresponding residue Phe-31 in murine DHFR were interchanged, and the impact on catalysis was evaluated by steady-state and pre-steady-state analysis. The E. coli L28F mutant increased the pH-independent kcat from 11 to 50 s-1 but had little effect on Km(H2F). An increase in the rate constant for dissociation of H4F from E.H4F.NH (from 12 to 80 s-1) was found to be largely responsible for the increase in kcat. Unexpectedly, the rate constant for hydride transfer increased from 950 to 4000 s-1 with little perturbation of NADPH and NADP+ binding to E. Consequently, the flux efficiency of the E. coli L28F mutant rose from 15% to 48% and suggests a role in genetic selection for this variable side chain. The murine F31L mutant decreased the pH-independent kcat from 28 to 4.8 s 1 but had little effect on Km(H2F). A decrease in the rate constant for dissociation of H4F from E.H4F.NH (from 40 to 22 s-1) and E.H4F (from 15 to 0.4 s 1) was found to be mainly responsible for the decrease in kcat. The rate constant for hydride transfer decreased from 9000 to 5000 s-1 with minor perturbation of NADPH binding. Thus, the free energy differences along the kinetic pathway were generally similar in magnitude but opposite in direction to those incurred by the E. coli L28F mutant. This conclusion implies that DHFR hydrophobic active-site side chains impart their characteristics individually and not collectively. PMID- 1510970 TI - Interfacial catalysis by phospholipase A2: the rate-limiting step for enzymatic turnover. AB - The kinetics of the phospholipase A2-catalyzed hydrolysis of bilayer vesicles and mixed micelles of several oxyglycero and thioglycero analogues of phospholipids have been studied. The results with vesicles show that, depending on the source of the enzyme, the rates of hydrolysis of the oxy-containing long-chain phosphatidylmethanols are 2.5- to 28-fold higher compared to the rates of hydrolysis of the analogous thio substrates. The oxygen to sulfur substitution does not significantly alter the affinities of the enzymes for the reaction products or calcium. Since it is unlikely that sulfur substitution changes the rate constants for the formation and dissociation of the enzyme-product complex by the same factor, the element effects seen in the rates of hydrolysis of the oxy- and thioester phospholipids in vesicles are primarily due to a change in the rate constant for the chemical step of the catalytic turnover cycle. For bovine pancreatic phospholipase A2, various mutants with lower catalytic activity were used to show that the value of the element effect does not increase in the mutants. These results establish that, for the pancreatic phospholipase A2, the element effect is fully expressed, and the chemical step is fully rate-limiting for both oxyglycero and thioglycero phospholipids in vesicles. It was found that the element effect decreases from 7 to 1 when long-chain phosphatidylmethanols are present in micelles of a neutral diluent. This result suggests that the chemical step is not rate-limiting during the hydrolysis of these mixed micelle substrates. PMID- 1510971 TI - Enzymatic catalysis of prolyl isomerization in an unfolding protein. AB - Prolyl isomerases are able to accelerate slow steps in protein refolding that are limited in rate by cis/trans isomerizations of Xaa-Pro peptide bonds. We show here that prolyl isomerizations in the course of protein unfolding are also well catalyzed. To demonstrate catalysis we use cytoplasmic prolyl isomerase from Escherichia coli as the enzyme and reduced and carboxymethylated ribonuclease T1 as the substrate. This form of ribonuclease T1 without disulfide bonds is nativelike folded only in the presence of moderate concentrations of NaCl. Unfolding can be induced by reducing the NaCl concentration at ambient temperature and in the absence of denaturants. Under these conditions prolyl isomerase retains its activity and it catalyzes prolyl cis/trans isomerization in the unfolding protein. Under identical conditions within the NaCl-induced transition unfolding and refolding are catalyzed with equal efficiency. The stability of the protein and thus the final distribution of unfolded and folded molecules attained at equilibrium is unchanged in the presence of prolyl isomerase. These results demonstrate that prolyl isomerase functions in protein folding as an enzyme and catalyzes prolyl isomerization in either direction. PMID- 1510972 TI - Stereochemical outcome of the hydrolysis reaction catalyzed by the EcoRV restriction endonuclease. AB - The stereochemical course of the reaction catalyzed by the EcoRV restriction endonuclease has been determined. This endonuclease recognizes GATATC sequence and cuts between the central T and dA bases. The Rp isomer of d(GACGATsATCGTC) (this dodecamer contains a phosphorothioate rather than the usual phosphate group between the central T and dA residues, indicated by the s) was a substrate for the endonuclease. Performing this reaction in H2 18O gave [18O]dps(ATCGTC) (a pentamer containing an 18O-labeled 5'-phosphorothioate) which was converted to [18O]dAMPS with nuclease P1. This deoxynucleoside 5'-[18O]phosphorothioate was stereospecifically converted to [18O]dATP alpha S with adenylate kinase and pyruvate kinase [Brody, R. S., & Frey, P. A. (1981) Biochemistry 20, 1245-1251]. Analysis of the position of the 18O in this product by 31P NMR spectroscopy showed that it was in a bridging position between the alpha- and beta-phosphorus atoms. This indicates that the EcoRV hydrolysis proceeds with inversion of configuration at phosphorus. The simplest interpretation is that the mechanism of this endonuclease involves a direct in-line attack at phosphorus by H2O with a trigonal bipyramidal transition state. A covalent enzyme oligodeoxynucleotide species can be discounted as an intermediate. An identical result has been previously observed with the EcoR1 endonuclease [Connolly, B. A., Eckstein, F., & Pingoud, A. (1984) J. Biol. Chem. 259, 10760-10763]. X-ray crystallography has shown that both of these endonucleases contain a conserved array of amino acids at their active sites. Possible mechanistic roles for these conserved amino acids in the light of the stereochemical findings are discussed. PMID- 1510973 TI - Hepatitis A virus 3C proteinase substrate specificity. AB - Hepatitis A virus (HAV) 3C proteinase is responsible for processing the viral precursor polyprotein into mature proteins. The substrate specificity of recombinant hepatitis A 3C proteinase was investigated using a series of synthetic peptides representing putative polyprotein junction sequences. Two peptides, corresponding to the viral polyprotein 2B/2C and 2C/3A junctions, were determined to be cleaved most efficiently by the viral 3C proteinase. The kcat/Km values determined for the hydrolysis of a further series of 2B/2C peptides, in which C-terminal and N-terminal amino acids were systematically removed, revealed that P4 through P2' amino acids were necessary for efficient substrate cleavage. The substitution of Ala for amino acids in P1 and P4 positions decreased the rate of peptide hydrolysis by 100- and 10-fold, respectively, indicating that the side chains of Gln in P1 and Leu in P4 are important determinants of substrate specificity. Rates of hydrolysis measured for other P1- and P4-substituted peptides indicate that S1 is very specific for the Gln side chain whereas S4 requires only that the amino acid in P4 be hydrophobic. A continuous fluorescence quench assay was developed, allowing the determination of kcat/Km dependence on pH. The pH rate profile suggests that catalyzed peptide hydrolysis is dependent on deprotonation of a reactive group having a pKa of 6.2 (+/- 0.2). The results of tests with several proteinase inhibitors indicate that this cysteine proteinase, like other picornaviral 3C proteinases, is not a member of the papain family. PMID- 1510974 TI - Energetics of allosteric regulation in muscle pyruvate kinase. AB - The regulatory mechanism of rabbit muscle pyruvate kinase has been studied as a function of temperature in conjunction with phenylalanine, the allosteric inhibitor. The inhibitory effect of phenylalanine is modulated by temperature. At low temperatures, the presence of phenylalanine is almost inconsequential, but as the temperature increases so does the phenylalanine-dependent inhibition of the kinetic activity. In addition, the presence of phenylalanine induces cooperativity in the relation between velocity and substrate concentration. This effect is especially pronounced at elevated temperature. The kinetic data were analyzed using an equation that describes the steady-state kinetic velocity data as a function of five equilibrium constants and two rate constants. Van't Hoff analysis of the temperature dependence of the equilibrium constants determined by nonlinear curve fitting revealed that the interaction of pyruvate kinase with its substrate, phosphoenolpyruvate, is an enthalpy-driven process. This is consistent with an interaction that involves electrostatic forces, and indeed, phosphoenolpyruvate is a negatively charged substrate. In contrast, the interaction of pyruvate kinase with phenylalanine is strongly entropy driven. These results imply that the binding of phenylalanine involves hydrophobic interaction and are consistent with the basic concepts of strengthening of the hydrophobic effect with an increase in temperature. The effect of phenylalanine at high temperatures is the net consequence of weakening of substrate-enzyme interaction and significant strengthening of inhibitor binding to the inactive state of pyruvate kinase. The effects of salts were also studies. The results show that salts also exert a differential effect on the binding of substrate and inhibitor to the enzyme.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1510975 TI - Bioreductive activation of mitomycin C by DT-diaphorase. AB - The role of DT-diaphorase (DTD, EC 1.6.99.2) in the bioreductive activation of mitomycin C was examined using purified rat hepatic DTD. The formation of adducts with reduced glutathione (GSH), binding of [3H]mitomycin C to DNA, and mitomycin C-induced DNA interstrand cross-linking were used as indicators of bioactivation. Mitomycin C was metabolized by DTD in a pH-dependent manner with increasing amounts of metabolism observed as the pH was decreased from 7.8 to 5.8. The major metabolite observed during DTD-mediated reduction of mitomycin C was 2,7 diaminomitosene. GSH adduct formation, binding of [3H]mitomycin C and mitomycin C induced DNA interstrand cross-linking were observed during DTD-mediated metabolism. In agreement with the pH dependence of metabolism, increased bioactivation was observed at lower pH values. Temporal studies and experiments using authentic material showed that 2,7-diaminomitosene could be further metabolized by DTD resulting in the formation of mitosene adducts with GSH. DNA cross-linking during either chemical (sodium borohydride) or enzymatic (DTD) mediated reduction of mitomycin C could be observed at pH 7.4, but it increased as the pH was decreased to 5.8, showing the critical role of pH in the cross linking process. These data provide unequivocal evidence that the obligate two electron reductase DTD can bioactivate mitomycin C to reactive species which can form adducts with GSH and DNA and induce DNA cross-linking. The use of mitomycin C may be a viable approach to the therapy of tumors high in DTD activity, particularly when combined with strategies to lower tumor pH. PMID- 1510976 TI - Two-step binding mechanism for HIV protease inhibitors. AB - Rate constants for binding of five inhibitors of human immunodeficiency virus (HIV) protease were determined by stopped-flow spectrofluorometry. The two isomers of quinoline-2-carbonyl-Asn-Phe psi-[CH(OH)CH2N]Pro-O-t-Bu (R diastereomer = 1R; S diastereomer = 1S) quenched the protein fluorescence of HIV protease and thus provided a spectrofluorometric method to determine their binding rate constants. The dissociation rate constants for acetyl-Thr-Ile-Leu psi(CH2NH)Leu-Gln-Arg-NH2 (2), (carbobenzyloxy)-Phe psi[CH(OH)CH2N]Pro-O-t-Bu (3), and pepstatin were determined by trapping free enzyme with 1R as 2, 3, and pepstatin dissociated from the respective enzyme.inhibitor complex. Association rate constants of 1R, 2, and pepstatin were calculated from the time-dependent inhibition of protease-catalyzed hydrolysis of the fluorescent substrate (2 aminobenzoyl)-Thr-Ile-Nle-Phe(NO2)-Gln-Arg-NH2 (4). The kinetic data for binding of 1S to the protease fit a two-step mechanism. Kd values for these inhibitors were calculated from the rate constants for binding and were similar to the respective steady-state Ki values. PMID- 1510977 TI - Inhibition of 2,3-oxidosqualene cyclases. AB - Monocyclic and tricyclic compounds possessing a nitrogen atom situated at a position corresponding to the carbenium ion of high energy intermediates or transition states involved during cyclization of 2,3-oxidosqualene to tetra- and pentacyclic triterpenes have been synthesized. These compounds were tested as inhibitors of 2,3-oxidosqualene cycloartenol, lanosterol-, and beta(alpha)-amyrin cyclases in vitro and in vivo, and their affinity was compared to that of formerly synthesized 8-aza-bicyclic compounds [Taton et al. (1986) Biochem. Biophys. Res. Commun. 138, 764-770]. A monocyclic N-alkyl-hydroxypiperidine was shown to be the strongest inhibitor of the series upon cycloartenol-cyclase (I50 = 1 microM) from maize embryos but was much less effective on the beta(alpha) amyrin-cyclases from Rubus fruticosus suspension cultures or pea cotyledons. In contrast, 13-aza-tricyclic derivatives displayed little inhibition on 2,3 oxidosqualene cycloartenol-, lanosterol-, and beta(alpha)-amyrin-cyclases. The obtained data exemplify the differences existing in the cyclization process between cycloartenol- (lanosterol-) cyclases on one hand and beta(alpha)-amyrin cyclases on the other. The results are discussed with respect to current mechanisms postulated for 2,3-oxidosqualene cyclization. Because of its activity in vivo and in vitro the monocyclic N-alkyl-hydroxypiperidine appears to be a potent and promising tool to study sterol biosynthesis regulation. PMID- 1510978 TI - 13C NMR of cyanylated flavodoxin from Megasphaera elsdenii and of thiocyanate model compounds. AB - Both of the thiol groups of Megasphaera elsdenii flavodoxin have been cyanylated using 13C-enriched cyanide. This chemical modification increases the dissociation constant of the apoflavodoxin-flavin mononucleotide (FMN) complex from 0.4 nM to 2 microM. The thiocyanate carbons of the cyanylated cysteine residues in apoflavodoxin had 13C chemical shifts of 109.4 ppm and 112.2 ppm, which were replaced by signals at 115.5 ppm and 109.6 ppm when FMN was bound. The signals at 109.4 ppm and 112.2 ppm due to the cyanylated apoflavodoxin were unstable at 28 degrees C, and they were slowly replaced signals at 114.5 ppm and 115.3 ppm which are attributed to an inactive form of the apoprotein, which does not bind FMN. At alkaline pH values or after prolonged incubation at neutral pH, the signals at 114.5 ppm and 115.3 ppm were replaced by signals at approximately 171 ppm. On the basis of results obtained with model compounds, the signals at 171 ppm are assigned to the 2-imino carbon of the 2-iminothiazolidine ring formed by the cyclization of the appropriate thiocyanate group. After determining the chemical shift of the thiocyanate carbon of model compounds in a range of solvents, we conclude that the thiocyanate carbons will have a minimal chemical shift of approximately 109 ppm in apolar solvents which do not contain hydrogen bond donors. In water, a more polar hydrogen-bonding solvent, the chemical shift increases to approximately 115 ppm. We also conclude that the chemical shift of a thiocyanate carbon can be used as a probe of its molecular environment.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1510979 TI - Rotational resonance NMR study of the active site structure in bacteriorhodopsin: conformation of the Schiff base linkage. AB - Rotational resonance, a new solid-state NMR technique for determining internuclear distances, is used to measure a distance in the active site of bacteriorhodopsin (bR) that changes in different states of the protein. The experiments are targeted to the active site of bR through 13C labeling of both the retinal chromophore and the Lys side chains of the protein. The time course of the rotor-driven magnetization exchange between a pair of 13C nuclei is then observed to determine the dipolar coupling and therefore the internuclear distance. Using this approach, we have measured the distance from [14-13C]retinal to [epsilon-13C]Lys216 in dark-adapted bR in order to examine the structure of the retinal-protein linkage and its role in coupling the isomerizations of retinal to unidirectional proton transfer. This distance depends on the configuration of the intervening C=N bond. The 3.0 +/- 0.2 A distance observed in bR555 demonstrates that the C=N bond is syn, and the 4.1 +/- 0.3 A distance observed in bR568 demonstrates that the C=N bond is anti. These direct distance determinations independently confirm the configurations previously deduced from solid-state NMR chemical shift and resonance Raman vibrational spectra. The spectral selectivity of rotational resonance allows these two distances to be measured independently in a sample containing both bR555 and bR568; the presence of both states and of 25% lipid in the sample demonstrates the use of rotational resonance to measure an active site distance in a membrane protein with an effective molecular mass of about 85 kDa.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1510980 TI - Orientation factor in steady-state and time-resolved resonance energy transfer measurements. AB - Resonance energy transfer measurements provide a way to estimate distances between chromophores attached to different sites of macromolecules. There are two unknowns involved in resonance energy transfer measurements, the distance between two chromophores and their relative orientation. When static orientational disorder exists, the orientation factor, kappa 2, can vary from 0 to 4, leading to considerable uncertainty in estimation of distances. Fluorescence polarization anisotropy measurements can reduce the degree of uncertainty [Dale & Eisinger (1974) Biopolymers 13, 1573]. There may still be substantial error bounds for the average distance measurements. Time-resolved fluorescence measurements provide an "apparent" average distance and distance distribution containing contributions by both distance and orientation. The contribution of orientation to observed "apparent" average distance and distance distribution widths has been estimated for both simulated and real data. With a single unique distance as input in the simulation and with random but static orientation of donor and acceptor, the recovered average distance is very close to that of the input when the input distance is close to or larger than the Forster distance. The recovered width of apparent distance distribution can be substantial and it changes as a function of Forster distance to average distance ratio and as a function of Forster distance. Similar conclusions apply to the case where there is a real distance distribution. Motional averaging of the orientation was simulated by the Monte Carlo method to estimate the contribution of orientation when chromophores have certain degrees of mobility.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1510981 TI - Tryptophan contributions to the unusual circular dichroism of fd bacteriophage. AB - The circular dichroism (CD) spectrum of fd bacteriophage has a deep minimum at 222 nm characteristic of highly alpha-helical protein, but there is a shoulder at 208 nm rather than a minimum, with a 222/208-nm amplitude ratio near 1.5 rather than near 1. Oxidation of fd phage with the tryptophan reagent N-bromosuccinimide (NBS) changes the ratio. In this report, the NBS titration of fd is followed by CD and three other spectroscopies, the results of which yield an explanation of the unusual CD spectrum. Absorbance, fluorescence, and Raman data show the oxidation to have two phases, the first of which involves the destruction of tryptophan and the second, tryptophan and tyrosine. Raman spectra reveal the invariance of an environmentally-sensitive tyrosine Fermi resonance doublet during the first oxidative phase. Raman spectra also show that little or no change of alpha-helicity occurs in the first or second oxidation phase, although very slight changes in the helix parameters might be occurring. Concurrent with the destruction of tryptophan during the first phase is the appearance in CD difference spectra ([theta]NBS-treated fd - [theta]native fd) of positive maxima at 208-210 nm and negative maxima at 224 nm, with crossovers at 217 nm. Enormous difference ellipticities, per oxidized subunit of 50 amino acids, of +490,000 +/- 80,000 deg cm2 dmol-1 at 208 nm and -520,000 +/- 110,000 deg cm2 dmol-1 at 224 nm have been derived from the data.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1510982 TI - Fourier transform resonance Raman spectroscopy of phytochrome. AB - The Pr and Pfr forms of phytochrome in H2O and D2O have been studied by Fourier transform resonance Raman spectroscopy with near-infrared excitation (1064 nm). It is demonstrated that this technique is a powerful method for analyzing the chromophore structures of photosensitive pigments. The high spectral quality allows discussion of vibrational assignments based on an empirical approach using previously published data obtained from model compounds. The reduction in intensity of a high-frequency band assigned to the ring-C/D methine bridge vibration is an indication for the non-coplanarity of the ring D in Pfr. The high intensity of a C-H out-of-plane vibration also supports this hypothesis. In Pr, a broad peak at approximately 1100 cm-1 is assigned to an out-of-plane vibration of a strongly hydrogen-bonded pyrrole C=NH+ group. It is missing in Pfr, suggesting deprotonation of the corresponding ring during the transformation from Pr to Pfr. PMID- 1510983 TI - Probing the metal-binding sites of cod parvalbumin using europium(III) ion luminescence and diffusion-enhanced energy transfer. AB - Excitation spectroscopy of the 7F0----5D0 transition of Eu3+ and diffusion enhanced energy transfer are used to study metal-binding characteristics of the calcium-binding protein parvalbumin from codfish. Energy is transferred from Eu3+ ions occupying the CD- and EF-binding sites to the freely-diffusing Co(III) coordination complex energy acceptors: [Co(NH3)6]3+, [Co(NH3)5H2O]3+, [CoF(NH3)5]2+, [CoCl(NH3)5]2+, [Co(NO2)3(NH3)3], and [Co(ox)3]3-. In the absence of these inorganic energy acceptors, the excited-state lifetimes of Eu3+ bound to the CD and EF sites are indistinguishable, even in D2O; however, in the presence of the positively charged energy acceptor complexes, the Eu3+ probes in the cod parvalbumin have different excited-state lifetimes due to a greater energy transfer site from Eu3+ in the CD site than from this ion in the EF site. The observation of distinct lifetimes for Eu3+ in the two sites allows the study of the relative binding site affinities and selectivity, using other members of the lanthanide ion series. Our results indicate that during the course of a titration of the metal-free protein, Eu3+ fills the two sites simultaneously. Eu3+ is competitively displaced by other Ln3+ ions, with the CD site showing a preference for the larger Ln3+ ions while the EF site shows little, if any, competitive selectivity across the Ln3+ ion series. PMID- 1510984 TI - Circularly polarized luminescence from terbium(III) as a probe of metal ion binding in calcium-binding proteins. AB - A number of different experimental techniques have been used to probe the details of structural changes on the binding of Ca(II) to the large number of known calcium-binding proteins. The use of luminescent lanthanide(III) ions, especially terbium(III) and europium(III), as substitutional replacement for calcium(II), has led to a number of useful experiments from which important details concerning the metal ion coordination sites have been obtained. This work is concerned with the measurement of the circularly polarized luminescence (CPL) from the 5D4--- 7F5 transition of Tb(III) bound to the calcium binding sites of bovine trypsin, bovine brain calmodulin, and frog muscle parvalbumin. It is demonstrated that it is possible to make these polarization measurements from very dilute solutions (less than 20 microM) and monitor structural changes as equivalents of Tb(III) are added. It is shown that the two proteins that belong to the class of "EF hand" structures (calmodulin and parvalbumin) possess quite similar CPL line shapes, whereas Tb(III) bound to trypsin has a much different band structure. CPL results following competitive and consecutive binding of Ca(II) and Tb(III) bound to calmodulin are also reported and yield information concerning known differences between the sequence of binding of these two species. PMID- 1510985 TI - Influence of chromatin folding on transcription initiation and elongation by RNA polymerase III. AB - Nucleosomes were assembled onto either closed circular plasmids containing a single Xenopus 5S RNA gene or a linear tandemly repeated array of Lytechinus 5S RNA genes. Both chromatin templates were found to vary in their extent of compaction, depending upon the type and concentration of cation in solution. Compaction of these chromatin templates led to a significant inhibition of both transcription initiation and elongation by RNA polymerase III. Thus, the transcriptional repression observed after incorporation of genes into chromatin depends not only on occlusion of the promoter elements through direct contact with histones but also on compaction of nucleosomal arrays which occurs under the conditions of the transcription reactions. PMID- 1510986 TI - Incision at O6-methylguanine:thymine mispairs in DNA by extracts of human cells. AB - Human cell-free extracts were used to detect activities specifically incising O6 methylguanine (m6G) paired with C or T in DNA. A 45-bp double-stranded DNA containing one m6G across from a T (m6G:T) was the test substrate. Extracts from glioblastoma cell lines A172 and A1235 (lacking the m6G-specific repair protein m6G-DNA methyltransferase, MGMT) and colon carcinoma cell line HT29, containing MGMT, showed incision activities specific for the T strand of m6G:T [and G:T, as reported previously by Wiebauer and Jiricny (1989)] substrates, but did not cleave m6G:C (or G:C) substrates. Competition experiments showed that the activity was similar to, if not identical with, the activity in human cells that incises G:T mismatches. The incision sites were similar to those recognized by human G:T- or G:A-specific mismatch enzymes, i.e., the phosphodiester bonds both 3' and 5' to the poorly matched T, suggesting the glycolytic removal of the poorly matched T followed by backbone incisions by class I or II AP endonucleases. Three experiments in which MGMT was inactivated showed that the m6G:T incision activity was not simply due to a two-step mechanisms in which MGMT would first mediate conversion of the m6G:T substrate to a G:T substrate which would serve as a substrate for G:T incision. Extracts from HT29 contained a DNA binding factor, possibly DNA sequence-specific, that inhibited incision of the m6G:T (but not the G:T) substrate, that was removed by the addition of synthetic DNA to the reaction. PMID- 1510987 TI - Alternative structures for alternating poly(dA-dT) tracts: the structure of the B DNA decamer C-G-A-T-A-T-A-T-C-G. AB - The X-ray crystal structure of the decamer C-G-A-T-A-T-A-T-C-G has been solved with two contrasting cations, Ca2+ and Mg2+. Crystals with calcium are space group P2(1)2(1)2(1), cell dimensions a = 38.76 A, b = 40.06 A, and c = 33.73 A, and diffract to 1.7-A resolution. Crystals with magnesium have the same space group, cell dimensions a = 38.69 A, b = 39.56 A, and c = 33.64 A, and diffract to 2.0 A. Their structures were solved independently by molecular replacement, beginning with idealized Arnott B-DNA geometry. The calcium structure refined to R = 17.8% for the 3683 reflections greater than 2 sigma, with 404 DNA atoms, 95 solvent peaks, and 1 Ca(H2O)7(2+) ion. The magnesium structure refined to R = 16.5% for the 1852 reflections greater than 2 sigma, with 404 DNA atoms, 62 solvent peaks, and 1 Mg(H2O)6(2+) ion. The two structures are virtually identical and are isostructural with C-G-A-T-C-G-A-T-C-G [Grzeskowiak et al. (1991) J. Biol. Chem. 266, 8861-8883] and C-G-A-T-T-A-A-T-C-G [Quintana et al. (1992) J. Mol. Biol. 225, 375-395]. Comparison of C-G-A-T-A-T-A-T-C-G with C-G-C-A-T-A-T-A T-G-C-G [Yoon et al. (1988) Proc. Natl. Acad. Sci. U.S.A. 85, 6332-6336] shows that the expected alternation of twist angles is found in the central A-T-A-T-A-T region of the decamer (A-T small, T-A large), but the minor groove remains wide at the center, rather than narrow. Minor groove narrowing is produced, in these two structures, not by overwinding of the helix, but by an increase in base pair propeller. This analysis confirms the concept that poly(dA-dT).poly(dA-dT) is polymorphous, with different local conformations possible in different local environments. PMID- 1510988 TI - Differential isoprenylation of carboxy-terminal mutants of an inhibitory G protein alpha-subunit: neither farnesylation nor geranylgeranylation is sufficient for membrane attachment. AB - To determine the effect of protein isoprenylation with farnesyl vs geranylgeranyl groups on membrane association in vivo, COS cells were transfected with cDNAs encoding the wild-type G-protein alpha i1 (WT) subunit, the soluble nonmyristoylated G-protein alpha i1 glycine to alanine mutant (GA), a double mutant in which the carboxy-terminal residues CGLF of GA were mutated to CVLS (GA CVLS), and a double mutant in which the carboxy terminus of GA was mutated to CALL (GA-CALL). As opposed to the WT and GA proteins, the GA-CVLS and GA-CALL proteins were not pertussis toxin substrates nor were they recognized by antibodies that recognize the nonmutated alpha i1 carboxy terminus. Only the GA CVLS and GA-CALL proteins incorporated [3H]mevalonate in the form of a farnesyl and a geranylgeranyl moiety, respectively. Subcellular localization, as assessed by immunoblotting and immunoprecipitation, revealed that the WT protein localizes almost exclusively to the membrane fraction, whereas the GA, GA-CVLS, and GA-CALL proteins localize predominantly to the soluble fraction. The soluble GA-CVLS and GA-CALL proteins were not carboxyl methylated, but the small amount localized to the membrane was partially carboxyl methylated. These results indicate that neither farnesylation nor geranylgeranylation is sufficient alone to lead to membrane association. PMID- 1510989 TI - T-T base mismatches enhance drug binding at the branch site in a four-arm DNA junction. AB - Base mismatches--non Watson-Crick pairing between bases--can arise in duplex DNA as a consequence of mutational events or by recombination. In a duplex, the sequence of the two bases involved, and those flanking the site of mismatch, determines the local structure and extent of destabilization of the helix. Base mismatches can arise also in recombination of nonhomologous strands, and their occurrence in Holliday recombination intermediates can influence the outcome of general or specialized recombination events. We have previously reported that the branch site in a DNA junction can interact selectively with a variety of ligands. Here we describe the thermodynamics of junctions containing T-T mismatches flanking the branch and show that these structures bind methidium and other intercalators with higher affinity than junctions lacking mismatches. PMID- 1510990 TI - Linkage between ligand binding and control of tubulin conformation. AB - The effect of both antimitotic drugs and nucleotide analogues on the magnesium induced self-association of purified tubulin into 42S double rings has been examined by sedimentation velocity. In the absence of magnesium, all complexes sedimented as the 5.8S species. The binding of colchicine to tubulin led to a small but consistent (-0.1 to -0.2 kcal/mol) enhancement in the self-association of tubulin alpha-beta dimers. In the absence of nucleotide at the exchangeable site, tubulin retained a weak ability (K2 = 7.5 x 10(3) M-1) to self-associate, which was unchanged by the addition of guanosine or GMP. Analogues with altered P O-P bonds (GMPPCP, GMPPNP) did not support ring formation at the protein concentrations examined, although GMPPCP supported microtubule assembly. When the exchangeable site was occupied by nucleotides altered on the gamma-phosphate (GTP gamma S, GTP gamma F), rings were formed; tubulin-GTP gamma F formed rings to an extent slightly greater than did tubulin-GTP, and tubulin-GTP gamma S to about the same extent as tubulin-GDP. Both of these analogues are inhibitors of microtubule assembly. These results are consistent with a model [Melki, R., Carlier, M.-F., Pantaloni, D., & Timasheff, S. N. (1989) Biochemistry 28, 9143 9152] in which an equilibrium exists between straight (microtubule-forming) and curved (ring-forming) conformations of tubulin. Furthermore, the present results indicate that the "switch" which controls the nature of the final polymeric product via free energy linkages is the occupancy of the gamma-phosphate binding locus of the exchangeable site by a properly coordinated metal-nucleotide complex. PMID- 1510991 TI - Use of engineered proteins with internal tryptophan reporter groups and pertubation techniques to probe the mechanism of ligand-protein interactions: investigation of the mechanism of calcium binding to calmodulin. AB - Stopped-flow kinetic and fluorescence spectroscopic analyses, including solvent and temperature perturbations, of five isofunctional structural mutants of calmodulin indicate that calcium binding to calmodulin follows the order site III, site IV, site I, site II, with dissociation occurring in the reverse order. Each of the isofunctional structural mutants contains a single tryptophan residue, introduced by site-specific mutagenesis, as an internal spectroscopic reporter group that was used as a probe of local conformational change. Calcium binding was studied by using flow dialysis or by using fluorescence spectroscopy and monitoring the change in the single tryptophan residue in each calcium binding site. Calcium removal was examined by using EDTA and monitoring tryptophan fluorescence or by using Quin 2 and monitoring the change in the chromophoric chelator. Computational analysis of the data suggests a rate limiting step for dissociation between calcium removal from sites I/II and sites III/IV. Unexpected results with the site IV isofunctional mutant (Q135W-CaM) indicated cross-talk between the amino and carboxyl terminal halves of CaM during the calcium-binding mechanism. Studies with ethylene glycol provided empirical data that suggest the functional importance of the electrostatic potential of CaM, or the molarity of water, in the calcium-binding process. Altogether, the data allowed a kinetic extension of the sequential, cooperative model for calcium binding to calmodulin and provided values for additional parameters in the model of calcium binding to CaM, a prototypical member of the family of proteins required for calcium signal transduction in eukaryotic cells.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1510992 TI - Low-lying electronic states of carotenoids. AB - Four all-trans carotenoids, spheroidene, 3,4-dihydrospheroidene, 3,4,5,6 tetrahydrospheroidene, and 3,4,7,8-tetrahydrospheroidene, have been purified using HPLC techniques and analyzed using absorption, fluorescence and fluorescence excitation spectroscopy of room temperature solutions. This series of molecules, for which the extent of pi-electron conjugation decreases from 10 to seven carbon-carbon double bonds, exhibits a systematic crossover from S2--- S0 (1(1)Bu----1(1)Ag) to S1----S0 (2(1)Ag----1(1)Ag) emission with decreasing chain length. Extrapolation of the S1----S0 transition energies indicates that the 2(1)Ag states of longer carotenoids have considerably lower energies than previously thought. The energies of the S1 states of spheroidenes and other long carotenoids are correlated with the S1 energies of their chlorophyll partners in antenna complexes of photosynthetic systems. Implications for energy transfer in photosynthetic antenna are discussed. PMID- 1510993 TI - Bidirectional transport of spermine in rat liver mitochondria. AB - Further study of the mitochondrial transport of spermine (Toninello et al. (1988) J. Biol. Chem. 263, 19407) shows that, after loading rat liver mitochondria with [14C]spermine and [32P]phosphate, these components are released together into the surrounding medium by adding mersalyl or N-ethylmaleimide. On later addition of dithioerythritol, both are recaptured, but if acetate or nigericin are added instead, only spermine re-enters and there is continued export of phosphate. This bidirectional transport of spermine in and out mitochondria is driven, respectively, by membrane potential and pH gradient at constant protonmotive force. Results using [14C]spermine or [32P]phosphate, in conjunction with the their unlabelled isomers and with or without carbonyl cyanide/p trifuloromethoxyphenylhydrazone (FCCP) present suggest that there is a continuous energy-dependent efflux-influx cycling of spermine and phosphate. PMID- 1510994 TI - G-protein-regulated phospholipases C, D and A2-mediated signalling in neutrophils. PMID- 1510995 TI - What we can learn from the effects of thiol reagents on transport proteins. AB - Many secondary membrane transport systems contain reactive sulfhydryl groups. In this review the applications of SH reagents for analyzing the role of sulfhydryl groups in membrane transport systems will be discussed. First an overview will be given of the more important reagents, that have been used to study SH-groups in membrane transport systems, and examples will be given of transport proteins in which the role of cysteines have been analyzed. An important application of SH reagents to label transport proteins using various SH-reagents modified with fluorescent- or spin-label moieties will be discussed. Two general models are shown which have been proposed to explain the role of sulfhydryl groups in some membrane transport systems. PMID- 1510996 TI - Sterically stabilized liposomes. AB - Many recent reports have demonstrated that rapid uptake of liposomes in vivo by cells of the mononuclear phagocytic system (MPS), which has restricted their therapeutic utility, can be overcome by incorporation of lipids derivatized with the hydrophilic polymer polyethylene glycol (PEG). The structure-function relationship of PEG-derivatized phosphatidylethanolamine (PEG-PE) has been examined by measurement of blood lifetime and tissue distribution in both mice and rats. The results are reviewed and contrasted with those from liposomes without PEG-PE or other surface modifications. With a PEG molecular weight in the range of 1000 to 5000, prolonged circulation and reduced MPS uptake is achieved. After 24 h, up to 35% of the injected dose remains in the blood and less than 10% is taken up by the two major organs of the MPS, liver and spleen, compared with 1% and up to 50%, respectively, for liposomes without PEG-PE. Other important advantages of PEG-PE have been identified: prolonged circulation is independent of liposome cholesterol content, degree of hydrocarbon chain saturation in either the PC or the PE lipid anchor, lipid dose, or addition of most other negatively charged lipids. This versatility in lipid composition and dose is important for controlling drug release in a liposome-based therapeutic agent. Steric stabilization has been proposed as a theoretical basis for the results and some initial results testing this hypothesis have been reported. A description of a theoretical model is presented here and evaluated with the data available. The results are compared with other particulate drug carriers and the range of potential applications are considered. PMID- 1510997 TI - Phosphatidylethanolamine liposomes: drug delivery, gene transfer and immunodiagnostic applications. PMID- 1510998 TI - From contractile vacuole to leaky epithelia. Coupling between salt and water fluxes in biological membranes. PMID- 1510999 TI - Calcium and calmodulin function in the cell nucleus. PMID- 1511000 TI - Detection and time-course analysis of phospholipid hydroperoxide in soybean seedlings after treatment with fungal elicitor, by chemiluminescence-HPLC assay. AB - Direct evidence for the existence of phosphatidylcholine hydroperoxide (PCOOH) and the determination of the changes in PCOOH after treatment of soybean seedlings with fungal elicitor, were examined using chemiluminescence-HPLC of hydroperoxide specific assay. PCOOH was transiently accumulated within 6 h after elicitor treatment but such an event was not observed in control plants, thus suggesting that accumulation of PCOOH was a response to fungal elicitor in the host plant. The result suggested that singlet oxygen had participated in the lipid hydroperoxidation, since non-conjugated fatty acid hydroperoxide isomers due to the singlet oxygen oxidation were detected in the phospholipid fraction. The reaction of lipid hydroperoxidation, preceding the induction of a defense compound, may be involved in the triggering of a plant defense mechanism against fungal invasion. PMID- 1511001 TI - Purification and characterization of a high-affinity binding protein for pancreatic-type phospholipase A2. AB - A high-affinity and specific binding site for mammalian group I phospholipase A2 (PLA2-I) was found on the membranes of bovine corpus luteum. Affinity labeling experiments revealed that PLA2-I binds to a single polypeptide with a mass of 190 200 kDa. The PLA2-I binding protein in the membranes was solubilized in an active form with n-octyl beta-D-thioglucoside, and then purified approx. 16,000-fold. The purification procedures consisted of diethylaminoethyl-Sephacel chromatography, PLA2-I-affinity gel chromatography and gel-filtration high performance liquid chromatography on a TSKgel G3,000SWXL column. The final preparation migrated as a single molecular species of 190 kDa on sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE), and identification of the 190 kDa protein as the PLA2-I binding protein was demonstrated by ligand blotting analysis. The purified protein possessed a binding capacity with high affinity and specificity for a mammalian mature type of PLA2-I. Treatment of the purified material with N-glycosidase F resulted in increased mobility of the protein on SDS-PAGE as well as considerable abolition of the PLA2-I binding activity, thus suggesting the requirement of the carbohydrate moiety of the PLA2-I binding protein for receptor-ligand interactions. PMID- 1511002 TI - Amphipathic poly(ethylene glycol) 5000-stabilized dioleoylphosphatidylethanolamine liposomes accumulate in spleen. AB - Relatively small liposomes (d less than 200 nm) composed of dioleoylphosphatidylethanolamine (DOPE) and cholesterol (Chol) and containing dioleoyl-N-(monomethoxypoly(ethylene glycol)succinyl)phosphatidylethanolamine (PEG-PE), with PEG of M(r) 5000 (PEG5000-PE), accumulate in the spleen (approximately 40% i.v. injected dose), unlike dioleoylphosphatidylcholine (DOPC)/Chol/PEG5000-PE liposomes of similar size, which show prolonged circulation in the blood. Spleen accumulation was dependent on the injection dose, PEG-PE concentration, and the PEG chain length. The DOPE/Chol/PEG5000-PE liposomes are plasma stable and morphologically indistinguishable from DOPC/Chol/PEG5000-PE liposomes. These results reveal the significance of the matrix lipid in determining the circulation time of PEG-PE-containing liposomes, and are relevant to the design of liposomes which avoid or accumulate in the spleen. PMID- 1511003 TI - Cholesteryl ester transfer protein promotes the association of HDL apolipoproteins A-I and A-II with LDL: potentiation by oleic acid. AB - The association of apolipoprotein (apo) A-I and apo A-II with apo-B-containing particles was measured after incubation at 37 degrees C of either total plasma or low-density lipoproteins (LDL) and high-density lipoproteins-3 (HDL3) in the presence of partially purified cholesteryl ester transfer protein (CETP). At the end of the incubation, apo-B-containing lipoproteins were separated by immunoprecipitation with an anti-apo B gamma-globulin fraction. In mixtures containing LDL and HDL3, either maintained at 4 degrees C or incubated at 37 degrees C, optimal concentrations of anti-apo B antibodies induced the precipitation of more than 95% of apo B without precipitation of apo A-I and apo A-II. When total plasma was incubated at 37 degrees C for 24 h, a significant proportion of apo A-I and apo A-II became associated with apo-B-containing lipoproteins. The fraction of HDL apoproteins associated with apo-B-containing lipoproteins was significantly reduced when plasma was supplemented with TP2 anti CETP monoclonal antibodies, which are known to inhibit CETP activity. Incubation of LDL and HDL3 for 24 h at 37 degrees C in the presence of purified CETP also induced the association of a significant proportion of apo A-I and apo A-II with apo-B-containing particles. This effect was dependent on CETP concentration in the incubation mixtures and could be suppressed by the addition of anti-CETP monoclonal antibodies. While oleic acid alone, at a final concentration of 0.2 mmol/l, did not promote any association of HDL-apolipoproteins with LDL, it was able, at this concentration, to greatly enhance the CETP-mediated association of apo A-I and apo A-II with apo-B-containing particles. In the presence of both CETP and oleic acid, the association of apo A-I and apo A-II with apo-B containing particles was apparent within 3 h of commencing the incubation. Approximately 3 mol of apo A-I and 1 mol of apo A-II co-precipitated with each mol of apo B after a 24 h incubation of LDL, HDL3 and CETP. When oleic acid was added to the incubation mixture in addition to CETP, up to 5.5 mol of apo A-I and 2.3 mol of apo A-II were associated with each mol of apo B.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1511004 TI - Antioxidant role of cellular reduced coenzyme Q homologs and alpha-tocopherol in free radical-induced injury of hepatocytes isolated from rats fed diets with different vitamin E contents. AB - Reduced coenzyme Q9 (CoQ9H2) and reduced coenzyme Q10 (CoQ10H2) as well as alpha tocopherol (alpha-Toc) are known to be potent lipid-soluble antioxidants in mammalian tissues. Reduced coenzyme Q homolog (CoQnH2) appears to show antioxidant activity independent of that of alpha-Toc (Matsura, T., Yamada, K. and Kawasaki, T. (1992) Biochim. Biophys. Acta 1123, 309-315). To further confirm this, we have studied the antioxidant role of cellular CoQnH2 and alpha-Toc using hepatocytes isolated from rats fed diets containing deficient, sufficient, and excess amounts of vitamin E (VE). Cellular damage was induced with a hydrophilic radical initiator, 2,2'-azobis(2-amidinopropane) dihydrochloride (AAPH). The concentration of alpha-Toc in VE-deficient hepatocytes was approximately 1/12 that in VE-sufficient hepatocytes, whereas the concentration of alpha-Toc in VE excess hepatocytes was approximately 7-fold that in VE-sufficient hepatocytes. The molar ratios of alpha-Toc to CoQnH2 (CoQ9H2 plus CoQ10H2) in VE-deficient, sufficient and excess cells were 0.03, 0.33 and 2, respectively. In the hepatocytes in these three dietary groups, alpha-Toc status had little effect on the concentration of CoQ homologs. These hepatocytes were incubated with 50 mM AAPH for 4 h. The cell viability in all groups of hepatocytes decreased rapidly after 3 h of AAPH treatment, and was associated with the increase of lipid peroxides. The loss of cell viability and the increase of lipid peroxidation in VE-deficient cells were more pronounced than those in the hepatocytes of the other two groups. The endogenous CoQ9H2 content of each group of hepatocytes decreased linearly with a reciprocal increase in oxidized CoQ9 after addition of AAPH, whereas the decrease of endogenous CoQ10H2 in each group during AAPH treatment was much less than that of endogenous CoQ9H2. alpha-Toc in the three VE dietary groups of hepatocytes was also consumed without a time lag after addition of AAPH, and it was not spared by CoQnH2, even in VE-deficient cells where the CoQnH2 concentration was 38-fold that of alpha-Toc. These results indicate that CoQnH2, especially. CoQ9H2, is a lipid-soluble antioxidant, which is as effective as alpha-Toc in rat hepatocytes under the conditions employed in this study, and acts independently of alpha-Toc to inhibit lipid peroxidation. PMID- 1511005 TI - Albumin and fatty acid effects on the stimulated production of 1-O-hexadecyl-2 acetyl-sn-glycero-3-phosphocholine (PAF) by human polymorphonuclear leukocytes. AB - Production of platelet-activating factor (PAF) during opsonized zymosan stimulation of human polymorphonuclear leukocytes is dependent on the concentration of extracellular albumin and on the presence of exogenous fatty acids. Fatty acid-free albumin caused a concentration-dependent increase in PAF synthesis up to 5% albumin concentrations (w/v) where the amount of PAF produced was three- to four-fold higher than in controls containing no albumin. The addition of free fatty acids, particularly arachidonic acid and palmitic acid, to 5% fatty acid-free albumin media caused a concentration-dependent decrease in PAF synthesis. A 50% inhibition of PAF synthesis was observed at an arachidonic acid concentration of 120 microM and at a palmitic acid concentration of 100 microM. The inhibition of PAF production by palmitic acid was also dependent on the concentration of extracellular albumin. In 0.5% fatty acid-free albumin media, a palmitic acid concentration of 40 microM produced a 50% inhibition in PAF synthesis. The addition of palmitic acid did not affect the release of endogenous arachidonic acid during stimulation. In contrast, the addition of stearic acid up to 120 microM in 5% fatty acid-free albumin media had no effect on PAF production. The different inhibitory effects of palmitic acid and stearic acid on PAF production may be related to differences in intracellular utilization of these two fatty acids during cell stimulation. PMID- 1511006 TI - Binary phase behavior of angiotoxic oxidized cholesterols with cholesterol. AB - Binary phase diagrams of oxidized cholesterols with cholesterol were constructed in order to find a possible physical mechanism for these cytotoxic sterols as disruptors of cell membranes. Two compounds, 25-hydroxycholesterol and 7 ketocholesterol, behave similarly in solids with cholesterol, i.e., continuous solubility can be demonstrated over all concentrations with some tendency for individual molecular species to cluster in the liquid state. However, the two compounds have greatly different solubilities in phospholipid bilayers. The interaction of cholesterol with cholestane 3 beta, 5 alpha,6 beta-triol differs from that of the other two binaries since these molecules form a eutectic. This compound has been found to be soluble in phospholipid bilayers. Hence, from available evidence, the three oxidized cholesterols must employ different mechanisms for disruption of cell membranes, depending on which membrane component can most easily solubilize each. PMID- 1511007 TI - Nucleotide sequence of a fragment of the rat tryptophan oxygenase gene showing high affinity to glucocorticoid receptor in vitro. AB - A nucleotide sequence (3.2 kb) of a DNA region located approximately between introns 4 and 7 of the rat tryptophan oxygenase gene was determined. Using filter binding studies and monoclonal antibodies against the glucocorticoid receptor a high affinity binding of this region to the glucocorticoid receptor was demonstrated. PMID- 1511008 TI - Molecular cloning and DNA sequence analysis of cDNA encoding chicken homologue of the Bcl-2 oncoprotein. AB - We have isolated a 2228 bp cDNA clone encoding a chicken homologue of the human Bcl-2 oncoprotein by low-stringency hybridization screening of a lambda gt10 cDNA library derived from a chicken B-cell lymphoma. DNA sequence analysis of this cDNA revealed an open reading frame predicting a polypeptide of 232 amino acids and an M(r) of 25,839. The predicted protein is highly homologous to the human (73%) and mouse (70%) Bcl-2 proteins, and contains a hydrophobic stretch of amino acids within its carboxyl-end (213-229) consistent with an integral membrane protein. Areas of very high sequence homology shared by all three Bcl-2 proteins at the NH2-terminus (amino acids 1-33) and within the last 150 amino acids of these proteins suggest the presence of at least two evolutionarily conserved domains within the family of Bcl-2 proteins that may be important either for their targeting to mitochondria or their ability to block programmed cell death. PMID- 1511009 TI - Enriched sources of Escherichia coli replication proteins. The dnaG primase is a zinc metalloprotein. AB - Primase, the product of the Escherichia coli dnaG gene, is the enzyme responsible for RNA primer synthesis on both template strands at replication forks during chromosomal DNA synthesis. The dnaG gene was modified by replacement of the natural ribosome-binding site with one complementary to the 3' end of 16S rRNA, and then inserted downstream of tandem bacteriophage lambda PR and PL promoters in the pUC9-derived vector pCE30. Following thermal induction of transcription, the resulting plasmid pPL195 directed synthesis of primase activity to levels corresponding to approx. 120,000 molecules per cell. The overproduced protein was soluble and was readily purified in high yield (31 mg per 1 of culture). Purified primase was monomeric, was fully active in priming replication at the bacteriophage G4 complementary strand origin, and was shown to contain 0.92 +/- 0.08 g atom of tightly-bound zinc per mol of protein. Potential zinc-binding amino-acid residues near the N-terminus of the protein were identified. Although a mutant primase lacking 27 amino acid residues from the N-terminus was partly soluble, it was completely inactive. PMID- 1511010 TI - Authentic temperature-regulation of a heat shock gene inserted into yeast on a high copy number vector. Influences of overexpression of HSP90 protein on high temperature growth and thermotolerance. AB - Heat shock protein HSP90 is relatively abundant in eukaryotic cells even in the absence of heat shock. Its precise function is still unclear, although it is apparently required in higher levels for growth at high temperatures. In this study Saccharomyces cerevisiae transformants were constructed with 50-150 copies of the homologous heat-inducible gene for HSP90 (HSP82) present on a high copy number episomal vector. These transformants were then used to demonstrate: (i) that this heat shock gene displays essentially normal regulation when present in yeast at high copy numbers; (ii) that yeast is an expression host suitable for the high level synthesis of HSP90; and (iii) that increasing normal cellular levels of HSP90 affects a number of physiological properties. The HSP82 gene is normally single-copy in the haploid yeast genome, yet even at 50 to 150 copies per cell it displayed almost normal basal and heat shock-induced levels of expression. Proper regulation of the heat shock element sequence controlling HSP82 is therefore not lost at high gene copy levels. In unstressed cultures in exponential growth at 25 degrees C the low basal expression of the multiple HSP82 gene copies caused a 3 to 7-fold HSP90 overproduction, but HSP90 levels increased 10-fold to 30-40% of total cell protein following temperature upshift to 39 degrees C for 75 min. Heat induction of the chromosomal genes for other heat shock proteins in the same cells was not suppressed relative to cells which were isogenic but for the possession of just a single HSP82 gene, this constituting further evidence that yeast can authentically regulate a large number of heat shock genes. HSP90 overproduction was not protective against heat killing, causing strain-dependent reductions in growth at 37.5 degrees C and in thermotolerance. PMID- 1511011 TI - Isolation and characterization of a cdc 2 cDNA from Dictyostelium discoideum. AB - A cdc2 homologous sequence was amplified from Dictyostelium discoideum by the polymerase chain reaction and used to isolate several cDNA clones. The amino acid sequence encoded by these cDNAs exhibited approx. 60% identity to the Cdc2 proteins of other species. A cDNA containing the entire coding sequence complemented the temperature sensitive cdc28 mutant of Saccharomyces cerevisiae, although growth of the transformants was slow and limited. Southern blot analysis of restriction digests under high stringency conditions provided evidence that Dictyostelium contains a single cdc2 gene, although at lower stringency multiple fragments were detected, suggesting the existence of a cdc2 gene family. Northern blot analysis of RNA from different stages of Dictyostelium development showed that cdc2 mRNA levels increased during aggregation and then decreased to low levels by the pseudoplasmodial stage of development. By contrast, cdc2 mRNA levels remained relatively constant as cells passed from exponential growth to the stationary phase. PMID- 1511012 TI - Electron microscopical projections of the large ribosomal subunit from Thermomyces lanuginosus. AB - Multivariate statistical analysis and hierarchical ascendant classification have been used to construct averages of two fundamental electron microscopical views of large ribosomal subunits from the thermophilic fungus Thermomyces lanuginosus. The first was roughly pentagonal in shape and corresponded to the canonical crown view seen in images of large subunits from prokaryotic species. The second and more prevalent projection was elliptical in shape, and by matching protuberances could be interpreted as the complex rotated from the crown orientation. Because of its ubiquity and consistency, this elongated view could potentially serve as the standard for structural comparisons of the large ribosomal subunit from eukaryotic organisms, and as the basis for a three-dimensional reconstruction. PMID- 1511013 TI - Cloning and sequencing of a human cDNA from cytolytic NK/T cells with homology to yeast SEC7. AB - Using the technique of subtractive hybridization (natural killer (NK) minus T helper cell line Jurkat), a human cDNA clone named B2-1 was isolated and sequenced. B2-1 transcripts are highly expressed in NK and peripheral T cells, but not in the T helper cell line used in the subtraction. Two overlapping cDNA clones contained 3309 bp, in agreement with a predicted size of 3.2 kb obtained by Northern blot analysis. The cDNA contained a 5' open reading frame encoding a 398 amino acid (aa) protein with a calculated M(r) of 46,383. The protein contains N-linked glycosylation sites and a site for phosphorylation by protein kinase C. Database homology searches show that the deduced protein is novel and has three discrete domains with significant homology to several structural proteins. The most striking homology was to yeast SEC7 in the central domain of the gene (57% identical over 466 bp) and also the protein level (42% identical amino acids; 39% conserved amino acids). SEC7 is a large protein (2008 amino acids) found on Golgi vesicles that plays a role in protein transport. PMID- 1511014 TI - The primary structure of a protein containing a putative [6Fe-6S] prismane cluster from Desulfovibrio desulfuricans (ATCC 27774). AB - The gene encoding a protein containing a novel iron sulfur cluster ([6Fe-6S]) has been cloned from Desulfovibrio desulfuricans ATCC 27774 and sequenced. An open reading frame was found encoding a 545 amino acid protein (M(r) 58,496). The amino acid sequence is highly homologous with that of the corresponding protein from D. vulgaris (Hildenborough) and contains a Cys-motif that may be involved in coordination of the Fe-S cluster. PMID- 1511015 TI - The complete nucleotide sequence of the gene (rpoD1) encoding the principal sigma factor of the RNA polymerase from the cyanobacterium Synechococcus sp. strain PCC7942. AB - The complete nucleotide sequence of rpoD1 gene from Synechococcus PCC7942 has been determined. The nucleotide data have indicated the presence of an open reading frame of 1155 base pairs encoding a polypeptide which shares the framework structure for principal sigma factors of eubacterial strains. PMID- 1511016 TI - Nucleotide and primary amino acid sequence of porcine lactoferrin. AB - A cDNA encoding porcine lactoferrin (pLF) was isolated from a porcine mammary gland lambda gt11 cDNA library using human lactoferrin cDNA as the hybridization probe. Nucleotide sequence analysis indicates that pLF is 686 amino acids in length and shares 72.6%, 70.7% and 62.2% overall amino acid sequence identity with bovine, human and murine lactoferrin, respectively. PMID- 1511017 TI - Sexual dysfunction in cancer patients. AB - As a result of the convergence of increased numbers of cancer survivors, heightened awareness of quality of life issues and improved methods of treatment with sex therapy, the problem of sexual dysfunction after cancer treatment is receiving increased attention. In this article, the recent literature is reviewed by tumor site, including breast, bladder, colorectal, gynecologic, testicular, prostate, and other malignancies. Limitations and advances in the available literature are discussed, and recommendations for future research and clinical work are made. PMID- 1511018 TI - Supportive care in marrow transplantation. AB - Marrow transplantation is now an accepted form of therapy for patients with aplastic anemia, genetic diseases, and a variety of malignant diseases. Intensive chemotherapy and radiotherapy regimens are necessary to eradicate cancer cells and allow engraftment of the transplanted marrow. Patients undergoing such treatment suffer prolonged marrow aplasia and immunosuppression and experience significant nonmarrow toxicities. This requires maximum supportive care including hyperalimentation, fluid and blood transfusions, antibacterial and antiviral prophylaxis, and measures to reduce organ toxicities and accelerate engraftment. The use of drugs to suppress the production of antitumor necrosis factor-alpha has shown promise in reducing the nonmarrow toxicities of the conditioning regimen. Prophylactic antibiotics that reduce gastrointestinal colonization with aerobic bacteria yet preserve anaerobic flora may more effectively reduce not only systemic bacteria but fungal infections as well. The impact of infections due to cytomegalovirus has been reduced by more effective prevention in patients who are cytomegalovirus negative and reactivation in patients who are cytomegalovirus positive. The use of recombinant growth factors will significantly reduce morbidity after transplantation by reducing the period of marrow aplasia. PMID- 1511020 TI - Pleural effusions. AB - Pleural effusions are a common development in patients with cancer. The optimal means of control are not defined, but systemic treatment is often effective in patients with drug-sensitive tumors. Local treatments advocated in the management of malignant pleural effusions differ in the means of drainage, the length of time pleural tubes are left in situ, and the type of intrapleural therapy administered. Randomized trials published in the past few months have suggested that bleomycin sulfate may be superior to tetracycline as a sclerosant and that mitoxantrone does not add to control of effusions compared with large-bore pleural tube alone placed at time of thoracoscopy. PMID- 1511019 TI - Bone metastases and tumor-induced hypercalcemia. AB - Tumor-induced hypercalcemia and tumor-induced osteolysis are essentially due to a marked increase in osteoclast-mediated bone resorption, although the kidneys play an important contributory role in the genesis of tumor-induced hypercalcemia. Parathyroid hormone-like protein plays an essential role in tumor-induced hypercalcemia, and maybe in tumor-induced osteolysis, but other factors could also be responsible for the osteoclast activation secondary to the neoplastic infiltration of the skeleton. Treatment of tumor-induced hypercalcemia essentially consists of volume repletion and administration of potent anti osteolytic drugs. The bisphosphonate pamidronate is particularly useful for that matter and a dose of 1.0 to 1.5 mg/kg can normalize serum calcium in about 90% of hypercalcemic cancer patients. The apparently low response rate of bone metastases to systemic antineoplastic therapy seems to essentially reflect the relative insensitivity of our current methods for assessing response in tumor induced osteolysis. Newly developed biochemical markers of bone turnover could be particularly useful for that matter. Bisphosphonates are the most potent of the available inhibitors of osteoclast activity. Prolonged administration of oral pamidronate could reduce by almost one half the complications of tumor-induced osteolysis, and repeated bisphosphonate infusions could induce a dramatic relief of bone pain in one third and a sclerosis of lytic lesions in one fourth of the cases. These data must, however, be confirmed in randomized, blinded trials and many questions remain unanswered concerning the optimal therapeutic schemes. Medical therapy of tumor-induced osteolysis by noncytotoxic means has nevertheless become a reality. PMID- 1511021 TI - Recent progress and current problems in management of invasive fungal infections in patients with neoplastic diseases. AB - Patients with neoplastic diseases are predisposed to develop invasive fungal infections as the result of impairments of host defense mechanisms due principally to pharmacologic immunosuppression resulting from intensive cytotoxic chemotherapy, ablative radiation therapy, and corticosteroids. Candida species, Aspergillus species, and emerging opportunistic fungal pathogens comprise the principal etiologic agents of opportunistic mycoses in cancer patients. This paper reviews the recent progress, particularly during the year of 1991, in management of invasive fungal infections and the current problems of invasive mycosis, which confront patients with neoplastic diseases. PMID- 1511022 TI - Cytogenetic and experimental models. AB - The sarcomas, particularly those of soft tissue origin, often contain characteristic immunohistochemical and cytogenetic features that are of diagnostic relevance. Over the past year, novel findings have been reported that are likely to improve present sarcoma diagnostic capabilities. Findings of particular interest have been reported for Ewing's sarcoma, peripheral primitive neuroectodermal tumor, rhabdomyosarcoma, and clear cell sarcoma. PMID- 1511023 TI - Osteosarcoma and other cancers of bone. AB - Because of great improvements in survival and reduction in amputations in patients with osteosarcoma, investigators in the various fields involved in diagnosis and care of these patients are making greater efforts to contribute to better knowledge of the disease and the effects of treatment. Recent developments include basic studies on genetic abnormalities, evaluation of the role of modern imaging in predicting chemo-induced tumor necrosis and in defining tumor margins, and research into new agents, with new combinations and schedules for increasing prognosis and reducing side effects. Major efforts are also being made by surgeons in the difficult field of reconstruction after bone resections. PMID- 1511024 TI - Advances in the diagnosis and management of sarcomas. AB - Cytogenetic alterations that characterize different histologic subtypes of soft tissue sarcomas have been identified. In a few situations, more precise chromosomal mapping has allowed identification of certain genes that may be involved in the development or tumor progression of sarcomas. Careful family histories must be elicited in sarcoma patients. While "cancer families" are rarely identified when screening close relatives of sarcoma patients, the discovery of the currently known tumor suppressor gene syndromes associated with germ line retinoblastoma gene and p53 gene defects were made possible by their association with sarcomas. Optimal management of primary sarcomas includes function-sparing complete resection and radiotherapy. Innovative radiotherapy, utilizing radiation sensitizers or brachytherapy, may increase local control in patients with unresectable tumors. New drugs are needed. Epirubicin and other anthracycline analogues do have significant activity; however, no other novel drugs have documented efficacy. Dose intensity is being explored with sarcoma trials providing the "vehicle" to evaluate new cytokines. Several mechanisms of doxorubicin resistance have been identified in cell lines and fresh tumors, including alterations in glutathione peroxidase activity and MDR-1 gene expression. These observations need to be taken to the clinic. PMID- 1511025 TI - Rhabdomyosarcoma and other soft tissue sarcomas of childhood. AB - Childhood rhabdomyosarcoma and the other soft tissue sarcomas of childhood are a heterogeneous group of tumors with many histologic subtypes, affecting multiple anatomic locations and requiring the care of subspecialists from a variety of disciplines. Epidemiologic studies of childhood sarcomas indicate that a familial predisposition to malignancy may contribute to tumorigenesis in a proportion of patients. Diagnosis of these tumors may be difficult; immunohistochemical and cytogenetic analysis is clearly important. Large cooperative group studies have answered important treatment questions in past years; these studies are now being analyzed for clues to effective treatment of specific histologic and anatomic subgroups. The Intergroup Rhabdomyosarcoma Study IV is now open and the questions addressed are reviewed. New developments in late effects of therapy for childhood sarcoma are considered. PMID- 1511026 TI - Ewing's sarcoma and extracranial primitive neuroectodermal tumors. AB - Ewing's sarcoma and primitive neuroectodermal tumor of bone and soft tissue are rare tumors, considered with the small round blue cell tumors of childhood. Recent advances link Ewing's sarcoma and primitive neuroectodermal tumor, and support the concept that these tumors represent stages of differentiation in a neoplasm of neuroectodermal origin. Advances in chemotherapy have resulted in the survival of the majority of patients presenting with these tumors. This review briefly outlines the year's literature regarding the histogenesis, biology, and treatment of this tumor. PMID- 1511027 TI - Histology, histochemistry, tumor and serum markers in gastrointestinal tract cancer. AB - Integration of morphologic and molecular information is being pursued as a result of more extensive use of in situ hybridization techniques. Oncogenes, gene products, and viral genomes involved in the genesis and progression of gastrointestinal tumors have been located in specific histotypes or tumor sectors. The main advances in this area relate to cell-matrix interactions and the biologic mechanisms of tumor invasion. Some aspects of the morphogenetic sequences of gastric and colorectal adenocarcinomas and hepatocellular carcinoma have been elucidated. Studies of DNA ploidy have furnished results consonant with carcinogenesis models envisaging sequential genome alterations due to genetic instability of the transformed cell. The prognostic role of DNA content in gastrointestinal tumors, however, has not been unequivocally established. Research on tumor markers has been directed toward the tissue expression and distribution of apomucins with different molecular structures. Evaluation of tumor markers in body fluids has proved inadequate for the early detection and screening of gastrointestinal neoplasia. Some interesting results have been reported with regard to the monitoring of gastric and colorectal carcinomas by means of serum tumor markers. PMID- 1511028 TI - The genetics, epidemiology, and early detection of gastrointestinal cancers. AB - Current recommendations for screening large populations for colorectal neoplasia have been promulgated by a number of researchers and authorities who generally agree that ongoing screening is justifiable in high-risk groups but not yet in average-risk groups. Nonetheless, it is thought to be justifiable to provide screening for average-risk individuals upon request. Choice of tools for screening remains under discussion. Colonoscopy is generally agreed to be justifiable in those patients with the highest risk, ie, members of families with a clear inherited tendency to develop colorectal cancer or those with a personal history of colorectal neoplasia. There is currently no agreement concerning the recommended tools for those with a weaker family history (one or two affected relatives), but regular fecal occult blood testing with occasional limited endoscopic examination of the bowel is usually favored. The new immunochemical based occult blood tests show great promise for improved sensitivity and specificity. The evidence of the association between Helicobacter pylori gastritis and gastric cancer has been strengthened by three studies that show that patients with gastric cancer are more likely to have had infection in the years (up to 20) prior to diagnosis. The relative risk for cancer when infected with H. pylori is 3.6 to 6, but many H. pylori-positive individuals do not develop gastric cancer and additional factors must be operative. Probably the most exciting development for gastroenterology in 1991 is the identification of the gene on chromosome 5, designated APC, which is responsible for familial adenomatous polyposis.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1511030 TI - Supportive care. PMID- 1511029 TI - Imaging of gastrointestinal malignancies. AB - Many advancements in the imaging of gastrointestinal malignancies have been seen in the past year. Endorectal ultrasound and magnetic resonance imaging with an endorectal surface coil allow for more accurate staging of the depth of bowel wall invasion by rectal carcinoma. Monoclonal antibody imaging may detect metastases not found by other modalities while computed tomography arterial portography and intraoperative ultrasound improve our ability to identify liver metastases. Endoscopic ultrasound is also useful in the preoperative assessment of esophageal cancer and pancreatic endocrine tumors. PMID- 1511031 TI - Sarcomas. PMID- 1511032 TI - Gastrointestinal tract. PMID- 1511033 TI - Determination of moxonidine (BDF 5895) in plasma by gas chromatography-negative ion chemical ionization mass spectrometry. AB - For the measurement of the pharmacokinetic behaviour of moxonidine, 4-chloro-5-(2 imidazolin-2-yl-amino)-6-methoxy-2-methylpyrimidine, an extremely sensitive analytical method was needed. The GC-MS method developed is specific and reliably detects moxonidine plasma levels down to 40 pg ml-1. Using negative ion chemical ionization (NICI) the M- fragment of the ditrifluoromethyl benzamide derivative of moxonidine (m/z 721) and the [M-HCl]- fragment of the ditrifluoromethyl benzamide derivative of clonidine (internal standard, m/z 673) were monitored in the selected ion monitoring mode, ensuring a specific and sensitive detection of the compounds. The validation process carried out included assay precision, repeatability, linearity, accuracy, stability and estimation of the detection and determination limits. The plasma-level time-curves and pharmacokinetic parameters from two volunteers after oral administration of 0.2 mg moxonidine are presented and demonstrate the practicability of the method in, for example, clinical studies. PMID- 1511034 TI - The assay and resolution of the beta-blocker atenolol from its related impurities in a tablet pharmaceutical dosage form. AB - For the complete resolution and determination of the beta-blocker atenolol and its manufacturing impurities a high-performance liquid chromatographic method is developed using structured optimization techniques. The method utilizes a 300 x 3.9 mm i.d. stainless steel column packed with mu Bondapak C18 and a mobile phase containing methanol-25 mM potassium dihydrogen orthophosphate containing 0.06% (v/v) dibutylamine (20:80, v/v) (pH 3.0). The flow rate of 1.0 ml min-1 is used and a detection wavelength of 226 nm. The linearity and repeatability are good for the present compound over the range 1.5-510.0 micrograms ml-1 (r greater than 0.99 and RSD 0.27%, n = 10). Application of the method to 50 and 100 mg tablets gave recoveries of 99% (w/w) and reproducibilities of (RSD) 1.1 and 0.52%, respectively (n = 5). The manufacturing impurities are found to be greater than 0.5% (w/w) of the atenolol peak. PMID- 1511035 TI - On-line phase-transfer catalysed dansylation of phenolic compounds followed by normal-phase liquid chromatography with fluorescence detection. AB - A study of the on-line phase-transfer catalysed dansylation of phenolic compounds is presented. The extraction-dansylation is performed in the extraction coil of a home-made flow-injection extraction unit. After phase separation, the organic phase is fed to a normal-phase liquid chromatographic system with fluorescence detection. Ethynyloestradiol, oestradiol and paracetamol are used as test compounds. The influence of temperature on the reaction is examined. Calibration graphs showed good linearity (r greater than 0.996) and limits of detection are satisfactory (8 x 10(-7) M for ethynyloestradiol, 2 x 10(-6) M for oestradiol and 5 x 10(-7) M for paracetamol). The method is not applicable for the assay of oxychinoline, phenylephrine and morphine. PMID- 1511036 TI - A sensitive and reproducible HPLC assay for doxorubicin and pirarubicin. AB - A high-performance liquid chromatographic method with spectrofluorometric detection has been developed for the analysis of doxorubicin (DOX), pirarubicin (PIRA) and their metabolite, doxorubicinol, in plasma. The detection was performed at 480 nm for excitation, and 590 nm for emission. The proposed technique is selective, reliable, and sensitive. The limit of quantification was 2 ng ml-1 for DOX and 5 ng ml-1 for PIRA. The reproducibility of the analytical method through statistical coefficients is approximately 5%. The accuracy of the method is good; the relative error is less than 5%. PMID- 1511037 TI - On-line dialysis, liquid chromatography and post-column reaction detection of oxytetracycline in salmon muscle extracts. AB - The development of a sensitive automated method for residue control of oxytetracycline (OTC) in salmon muscle is described. Tissue homogenate is dialysed and the dialysate enriched on a small on-line polystyrene column. OTC and the internal standard (tetracycline) are separated by HPLC on a polystyrene column using an ion-pair eluent system. The column effluent is mixed with sodium hydroxide and irradiated at 366 nm and the resulting derivatives monitored by means of a fluorescence detector (excitation: 358 nm, emission: 460 nm). By the method OTC is detected down to 5 ng g-1. The standard curve was linear (r = 0.9999) over the range 50-1000 ng g-1. Within-day and between-day relative standard deviations (n = 6) at 50 and 200 ng g-1 ranged from 1.0 to 1.7%. PMID- 1511038 TI - Spectrophotometric determination of amoxycillin and its dosage forms. PMID- 1511039 TI - O-phosphoamino acid analysis of phosphorylated proteins by gas chromatography with flame photometric detection. PMID- 1511040 TI - The thin-layer chromatography of some organomercurial antiseptics on cellulose thin layers with aqueous solvents. PMID- 1511041 TI - A column-switching liquid chromatography assay for the analysis of carboplatin in plasma ultrafiltrate. PMID- 1511042 TI - Lactate-containing versus bicarbonate-containing peritoneal dialysis solutions. PMID- 1511043 TI - Peritoneal dialysis research for the 1990s. PMID- 1511044 TI - Bicarbonate- versus lactate-based CAPD fluids: a biocompatibility study in rabbits. AB - Previous in vitro biocompatibility studies have shown bicarbonate-based continuous ambulatory peritoneal dialysis (CAPD) fluids to be superior to those based upon lactate/acetate. To evaluate these findings in vivo, 41 rabbits were subjected to CAPD for four weeks in a randomized prospective study using either Dianeal, a commercially available dialysis fluid containing lactate, or 87b, a bicarbonate-based CAPD fluid. Ten rabbits with CAPD catheters, which were flushed with a heparin solution every 36 hours, served as controls. None of the control rabbits showed clinical or histopathological signs of peritonitis, while 8 of 20 in the Dianeal group and 6 of 21 in the 87b group contracted peritonitis. Four rabbits in the Dianeal group had to be sacrificed early due to severe peritonitis. Post mortem examinations, including scanning and light microscopy, did not reveal any macroscopic or microscopic differences among the three groups of noninfected animals. No significant distinctions between the groups could be made for body temperature, weight gain, dialysate volume, dialysate differential leukocyte count, dialysate protein content, and food intake during the course of the study. In conclusion, the present animal model did not reveal any major difference in the biocompatibility between the lactate- and the bicarbonate-based CAPD fluids. PMID- 1511045 TI - Peritoneal clearances in hypertensive CAPD patients after oral administration of clonidine, enalapril, and nifedipine. AB - The authors investigated whether the reduction of arterial pressure, induced by the oral administration of clonidine (CLO), enalapril (EN), and nifedipine (NIF), has any effect on peritoneal transport rates. The study was performed in nine hypertensive patients undergoing continuous ambulatory peritoneal dialysis (CAPD). The patients were submitted to administration of CLO, EN, and NIF, each in randomized succession for two weeks, after withdrawal of any hypotensive therapy for eight days (washout period). The nine patients underwent a four-hour dwell exchange using a 2.27 g/dL glucose two-liter bag after washout and after each hypotensive period. The following parameters were analyzed: mean arterial pressure (MAP), performed in the sitting position; net ultrafiltration; effluent/initial dialysate glucose ratio (GL D/Do); peritoneal clearance of K, BUN, creatinine (Cr), phosphate, beta-2 microglobulin (beta 2), total proteins, and the ratio between beta 2 and Cr clearance. Moreover, residual renal Cr and beta 2 clearances were analyzed. The three drugs significantly reduced MAP at a similar rate. The peritoneal transport parameters after CLO were similar to the results in the washout period. On the contrary, after EN and NIF therapy, Cr and beta 2 clearances were significantly increased, and GL D/Do decreased in comparison to the washout period. The other peritoneal transport parameters after EN and NIF were similar to the washout period. Residual renal Cr and beta 2 clearances after the three drugs were similar to those in the washout. these data suggest that after two weeks of therapy with EN and NIF, glucose, Cr, and beta 2 peritoneal transports are influenced by these hypotensive drugs irrespective of the effect on the arterial pressure.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1511046 TI - Acquired renal cystic disease and its complications in continuous ambulatory peritoneal dialysis patients. AB - PURPOSE: To determine whether there is any difference in the prevalence of acquired cystic disease and malignancy of the kidney in patients on continuous ambulatory peritoneal dialysis (CAPD) and hemodialysis. DATA IDENTIFICATION: Relevant studies published from January 1983 to June 1991 were identified by manual search and MEDLINE search. STUDY SELECTION: We reviewed the studies in which acquired renal cystic disease and/or renal cell carcinoma developed in patients on CAPD. DATA EXTRACTION: Details of the prevalence of acquired cystic disease and renal malignancy as a complication of acquired cysts in CAPD patients were tabulated with the duration of treatment. RESULTS: Acquired cystic disease was observed in 195 of 425 CAPD patients (41.1%), which is comparable to the prevalence of 47.1% (520/1103) seen in hemodialysis patients. The overall prevalence of renal cell carcinoma accompanying acquired cystic disease in this series of CAPD patients was 2 of 375 (0.4%), which is comparable to the prevalence of 1.5% (17/1103) in hemodialysis patients. So far, eight other instances of renal cell carcinoma complicating acquired cystic disease in CAPD patients were described as case reports. Retroperitoneal bleeding due to the rupture of acquired cysts has been reported on a few occasions. CONCLUSION: In this review no differences were detected in the prevalence or severity of acquired renal cystic disease in patients treated with CAPD as compared with those on hemodialysis. Therefore, the incidence of complications associated with acquired cysts may also be the same for the two treatment modalities, although reports on such complications are rare. PMID- 1511047 TI - Weekly clearances of urea and creatinine on CAPD and NIPD. AB - Weekly creatinine clearance (Ccr) and weekly Curea/v (kt/v) are popular indices for quantitating the amount of peritoneal dialysis provided. Studies were undertaken on 44 patients on continuous ambulatory peritoneal dialysis (CAPD) and 10 patients on nightly intermittent peritoneal dialysis (NIPD) to compare relationships of weekly creatinine clearance to weekly urea clearance (Curea) divided by total body water (v). With a long cycle therapy such as CAPD, the ratio of weekly Ccr to weekly kt/v is higher than with a short cycle technique, such as NIPD, in the same patient. If patients are shifted from CAPD to NIPD maintaining the same weekly kt/v, the weekly Ccr will decrease. If patients are shifted from CAPD to NIPD maintaining the same weekly Ccr, then the weekly kt/v will increase. The clinical implications of these observations are unknown, but should be kept in mind for future studies comparing CAPD and NIPD. PMID- 1511048 TI - Tidal peritoneal dialysis: preliminary experience. AB - OBJECTIVES: To determine the feasibility of home tidal peritoneal dialysis (TPD) and to assess whether eight hours of TPD can achieve uremia control and urea removal equal to that of continuous cycling peritoneal dialysis (CCPD). DESIGN: An open enrollment pilot study. SETTING: The Home Dialysis Training Center of the University of Iowa Hospitals and Clinics, a tertiary care teaching hospital. PATIENTS: Nine patients experienced with CCPD and living 80 km to 280 km from the dialysis center began TPD, because they wished to decrease their dialysis time. INTERVENTIONS: Following baseline measurements, each patient was taught to perform TPD. TPD consisted of an initial fill volume of 40 mL/kg, a residual volume approximately 20 mL/kg, and tidal exchanges of 10 to 20 mL/kg to achieve the desired hourly flow rate. Clinic assessments took place every four to six weeks, and prescriptions were subsequently altered to attain urea removal equal to that of CCPD. MEASUREMENTS: Patient interviews were used to determine TPD acceptance. Prior to each clinic visit, dialysate effluent volume and dialysis duration were recorded, and a sterile sample of the effluent was obtained for urea, creatinine, and total nitrogen measurement. RESULTS: Urea and creatinine clearances increased with dialysate flow. Dialysate nonurea nitrogen was 3.0 +/- 0.2 mmol/kg/D and changed minimally with increasing dialysate volumes. Eight hours of TPD (initial fill: 40 mL/kg; residual volume: 20 mL/kg; tidal inflow: 20 mL/kg) with hourly tidal flow exceeding 40 mL/kg/hr and no daytime volume achieved urea removal equal to that of the patient's prior CCPD prescription. CONCLUSION: TPD can provide dialysis equal to that of CCPD within a shorter amount of time (eight vs ten hours), but uses a greater volume of dialysate (16.0 L for TPD vs 9.5 L for CCPD). PMID- 1511049 TI - Comparison of exit-site infections in disconnect versus nondisconnect systems for peritoneal dialysis. AB - OBJECTIVE: To determine if disconnect systems reduce the incidence of exit-site infections when compared to nondisconnect systems. DESIGN: We prospectively monitored exit-site infections and peritonitis rates in 96 disconnect patients (Y set, automated peritoneal dialysis (APD)) and 60 nondisconnect patients (spike, ultraviolet connection device (UVXD)). SETTING: A freestanding chronic peritoneal dialysis unit staffed by physicians from both a medical school and a private setting. PATIENTS: All patients who began peritoneal dialysis at our unit were monitored, regardless of cause of end-stage renal disease (ESRD) or age. INTERVENTION: Patients were dialyzed using the system (Y-set, spike, etc.) most appropriate for their life-style and their ability to administer self-care. MAIN OUTCOME: We attempted to follow disconnect and nondisconnect patients for a similar median time on dialysis and compared differences in exit-site infections. RESULTS: Peritonitis rates (episodes/pt year) were reduced for disconnect (0.60) versus nondisconnect (0.99) systems (p = 0.0006). Despite the marked reduction in peritonitis rates, there was no difference in exit-site infection rates (0.35 vs 0.38), the time to the first exit-site infection, or the time to the first catheter removal for disconnect versus nondisconnect groups. When individual systems were compared, differences in exit-site infection rates (episodes/pt years) were noted (0.62,spike; 0.26,UVXD; 0.32,Y-set; 0.41,APD). CONCLUSION: We found no overall difference in exit-site infection rates for disconnect versus nondisconnect systems, despite a reduction in peritonitis rates for disconnect systems. PMID- 1511050 TI - Effect of long-term therapy with 1.25 mmol/L calcium peritoneal dialysis fluid on the incidence of peritonitis in CAPD. PMID- 1511051 TI - Pseudomonas peritonitis with white blood cell capillary margination and distal digital necrosis in a patient on CAPD. PMID- 1511052 TI - Pyopneumothorax with bronchofleural fistula following tetracycline pleurodesis in a patient on CAPD. PMID- 1511053 TI - Fluconazole serum, urine, and dialysate levels in CAPD patients. PMID- 1511054 TI - Toxicity of disinfectants to peritoneal membrane. PMID- 1511055 TI - Erythropoietin treatment does not improve uremic pruritus. PMID- 1511056 TI - Literature. July-September 1992. PMID- 1511057 TI - Coexistence of essential thrombocythemia and multiple myeloma. AB - We describe a patient with essential thrombocythemia (ET) who developed multiple myeloma (MM) 5 years after the initial diagnosis. A review of the literature revealed no additional reports of the association of these two diseases. Development of MM was not related to treatment of essential thrombocythemia. This association suggests an alteration at the pluripotential stem cell level. PMID- 1511058 TI - Elliptocytosis associated with an abnormal alpha glycophorin. AB - A case of elliptocytosis associated with an undescribed abnormal alpha glycophorin (alpha GP) is reported. Using immunoblotting techniques, a clear-cut minor band 6' was detected emerging just behind the monomer of delta GP (band 6) when probed with anti-alpha GP antiserum. It also reacted with anti-peptide C antiserum, suggesting that this new band with a molecular weight of 24 K is related to the structural alteration of alpha GP and not delta GP. The erythrocyte membrane proteins of the patient exhibited a quite normal pattern, with a normal alpha spectrin/beta spectrin ratio, but the reaction with anti protein 4.1 serum confirmed the increase in proteolytic susceptibility of her protein 4.1. The results of DNA mapping implied that the abnormality may be due to a short deletion of the heterozygote. The significance of deviation involving the alpha GP and protein 4.1 to the elliptocytic change of erythrocyte shape is briefly discussed. PMID- 1511059 TI - Blood transfusion in marrow graft recipients. AB - Of 182 consecutive patients undergoing allogeneic bone marrow transplantation (BMT), the relative numbers of those who received red blood cells (RBC), platelets (PLT), and granulocytes were 82%, 96%, and 26%, respectively. The transfused patients received an average of 1.26 (SD +/- 2.0) RBC units, 9.41 (SD +/- 13.2) PLT transfusions, and 0.33 (SD +/- 1.1) granulocyte concentrates per week per 50 kg body wt. in the period starting on the day of bone marrow transplantation (BMT) up to 60 days post BMT. The total number of units per transfused patient was 7.7 (range 1-63) RBC, 55.2 (range 2-394) PLT and 6.2 (range 1-36) granulocytes in the same period. Patients with grades II-IV acute graft-versus-host disease (GVHD) needed more RBC and PLT (p less than 0.001) than patients with grades 0-I acute GVHD. Patients with late engraftment required more granulocyte and PLT transfusion than those with early engraftment (p less than 0.05). Patients with high-risk malignancy had greater need for RBC and PLT than "low-risk patients" (p less than 0.02 and p less than 0.01), respectively). Patients with major ABO-incompatible donors showed a greater need for RBC than patients with minor ABO incompatibility (p = 0.02) or ABO identical donors (p = 0.01). Patients with relatively poor estimated survival required the most RBC and PLT. PMID- 1511060 TI - Maintenance with low-dose cytarabine for acute myeloid leukemia in complete remission. AB - Thirty-four patients with acute myeloid leukemia (AML) in complete remission (CR), 30 of them aged over 60, received maintenance therapy scheduling four courses of low-dose cytarabine (LDA) 20 mg/m2/day in two subcutaneous injections for 3 weeks every 6 weeks. Each course was stopped when hematologic toxicity occurred, and doses of LDA were subsequently reduced by 50% for the following courses. During the first course of LDA, 15 patients needed blood and four patients platelet transfusions. Overall, 28 patients received four courses of LDA: 11 did not require any dose reduction, while 14 required one dose reduction and three needed two successive dose reductions. Two patients were hospitalized during maintenance. Median disease-free survival (DFS) is 308 days, with 16% of patients surviving at 5 years. Seven patients relapsed during the 168 days of maintenance, while ten of the 27 patients remaining at risk on day 169 relapsed during the 168 days following maintenance. We conclude that in AML in CR, the maximal dose of LDA tolerated by ambulatory patients is 10 mg/m2/day for 3 weeks. LDA seemed to delay relapse; however, precise assessment of the efficacy of this approach would require a randomized trial. PMID- 1511061 TI - Anticardiolipin antibodies and lupus anticoagulant in patients treated with different methods of renal replacement therapy in comparison to patients with systemic lupus erythematosus. AB - Antiphospholipid antibodies were found to be associated with certain clinical manifestations such as recurrent venous thrombosis or arterial occlusions in a wide spectrum of immune disorders [6]. We analyzed the plasma concentration of two isotypes (IgG, IgM) of anticardiolipin antibodies (ACA) and lupus anticoagulant (LAC) activity in 84 patients with end-stage renal disease. They were receiving different types of renal replacement therapy and had a high frequency of thrombotic vascular complications. The prevalence of positive tests and the mean ACA concentration obtained in the plasma of renal patients were compared with those in patients with systemic lupus erythematosus (SLE) and in healthy controls. When analyzed as a whole group, renal patients maintained on dialysis (n = 45: hemodialysis, n = 20; peritoneal dialysis) or with a functioning kidney transplant (n = 19) did not differ in mean ACA concentration and LAC activity (n = 84, ACA: IgG 10 +/- 7 U/ml, IgM 2 +/- 1 U/ml, LAC ratio: 1.0 +/- 0.2) from healthy subjects (n = 50, ACA: IgG 10 +/- 3, IgM 2 +/- 1 U/ml, LAC ratio: 1.0 +/- 0.1) but they had a higher incidence of raised IgG-ACA titers (renal replacement 14% vs. normal controls 4%, p less than 0.05). No significant correlation was found between thrombotic events and raised ACA or LAC activity in dialysis patients. In contrast, the proportion of SLE patients (n = 51) with a raised concentration of ACA was significantly higher (IgG: 69%, IgM: 29%) than that among patients with renal replacement therapy (IgG: 14%, IgM: 4%) or normal controls (IgG: 4%, IgM: 2%, p less than 0.002). Moreover, recurrent manifestations of thrombosis in SLE were associated with very high IgG-ACA (n = 11, IgG 117 +/- 91 U/ml) and LAC activity (LAC ratio: 2.4 +/- 0.7) in comparison to SLE patients without thrombotic events (n = 40, ACA: IgG 23 +/- 13). The results of our investigations demonstrate that the pathogenetic role of these phospholipid antibodies in end-stage renal disease is far from established. PMID- 1511062 TI - Monitoring prothrombin fragment 1 + 2 during initiation of oral anticoagulant therapy after intracoronary stenting. AB - Patients with intracoronary stent implantation are treated with aggressive anticoagulant and antiplatelet therapy consisting of high-dose heparin, phenprocoumon, acetylsalicylic acid, dipyridamole, and the infusion of dextran to prevent a subacute thrombotic occlusion of the stented segment. In an effort to optimize this treatment by reducing both imminent bleeding complications and subacute thrombotic occlusion, the concentrations of prothrombin fragment 1 + 2 (F 1 + 2) were determined after intracoronary Palmaz-Schatz stent implantation in 19 consecutive patients. The F 1 + 2 concentrations after stent implantation and before the initiation of oral anticoagulant therapy (OAT) were 0.35 nm/l and 0.25 0.53 nm/l (median and 25th-75th percentile), versus 0.74 nm/l and 0.52-0.78 nm/l, in healthy subjects and 0.61 nm/l and 0.30-1.02 nm/l in 15 patients with ongoing proximal DVT. Nine days after initiation of OAT, F 1 + 2 concentrations in both patient groups had not yet reached levels observed in patients with OAT in the stable state (0.16 nm/l, 0.12-0.26 nm/l; n = 76; P less than 0.0001 compared with healthy subjects; INR 2.0-4.5). Despite an INR greater than 2.0, accompanying heparinization was terminated on day 9. In two stented patients a minor bleeding complication arose after the removal of the arterial catheter. Subacute thrombotic occlusions were not observed. Since F 1 + 2 concentrations did not exceed the upper limit of normal range (1.11 nm/l) in any of the 19 patients, the therapeutic regimen was not changed. Monitoring F 1 + 2 may thus be helpful in introducing a more individual treatment if aggressive anticoagulation has to be performed. PMID- 1511063 TI - Cytogenetics in multiple myeloma and plasma cell leukemia: simultaneous cytogenetic and cytologic studies in 51 patients. AB - Cytogenetic studies in patients with multiple myeloma (MM) and plasma cell leukemia (PCL) have in general been largely unsuccessful. The investigation of mitoses of nonmalignant hematopoietic precursor cells, rather than mitoses of malignant plasma cells might account for the low percentage of pathological genetic findings. We investigated bone marrow (BM) cells of 51 patients both cytogenetically and cytologically. In patients with a normal karyotype (n = 39) nearly all mitoses examined cytologically (107/117) derived from granulopoietic or erythropoietic cell lineages. In contrast, 20/27 metaphases in patients with a pathological karyotype (n = 12) were found to be plasma cell mitoses. These findings may explain the low rate of chromosomal rearrangements in MM and may suggest that the real abnormality rate is considerably higher. PMID- 1511064 TI - Correction of neutropenia by GM-CSF in patients with a large granular lymphocyte proliferation. AB - The in vivo and in vitro effects of GM-CSF were tested in four patients with large granular lymphocyte proliferation (LGLP) and severe granulocytopenia. All patients had an increased percentage of LGL cells (greater than 20%), whereas 3/4 patients demonstrated rearranged T-cell-receptor genes. An effect on the peripheral granulocyte counts was noticed in 3/4 patients after 14 days of GM-CSF administration (5 micrograms/kg/day, subcutaneously); 2.5, 7, and 0.45 x 10(9)/l, respectively. These changes were associated with a two- to five-fold increase in monocytes and a strong increment in eosinophils. In one patient GM-CSF was not effective in increasing the granulocyte count. B lymphocytes showed a variable increase, ranging from 1.2-fold to 3.8-fold, while the number of NK cells remained almost constant during the GM-CSF treatment. No consistent effect of GM CSF on T lymphocytes was observed. These data suggest that GM-CSF may be a therapeutic option in some patients with LGLP complicated by granulocytopenia and/or infection. PMID- 1511065 TI - Iron status markers, serum ferritin and hemoglobin in 1359 Danish women in relation to menstruation, hormonal contraception, parity, and postmenopausal hormone treatment. AB - Iron status was assessed by measuring serum (S-) ferritin and hemoglobin (Hb) in a population survey comprising 1359 nonpregnant Danish women, in age cohorts of 30, 40, 50, and 60 years; 809 were premenopausal and 550 postmenopausal. Median age for menarche was 14 years, for menopause (artificial and natural) 48 years. Premenopausal women had lower S-ferritin (median 37 micrograms/l) than postmenopausal women (median 71 micrograms/l; p less than 0.0001). Of the premenopausal women, 17.7% had S-ferritin less than 15 micrograms/l (i.e., depleted iron stores), and 23.1% S-ferritin of 15-30 micrograms/l (i.e., small iron stores). Corresponding figures in postmenopausal women were 3.3% and 10.3%. Hb values in premenopausal women were mean 137 +/- 10 (SD) g/l (8.5 +/- 0.6 mmol/l) vs. 140 +/- 10 g/l (8.7 +/- 0.6 mmol/l) in postmenopausal women (p less than 0.0001); 4.1% of pre- and 3.3% of postmenopausal women had values less than 121 g/l (7.5 mmol/l). Iron deficiency anemia (i.e., S-ferritin less than 15 micrograms/l and Hb less than 121 g/l) was found in 2.6% of pre- and 0.36% of postmenopausal women. Premenopausal multipara had lower S-ferritin than nulli- and unipara (p less than 0.04). The use of oral contraceptives had a marked influence on iron stores; premenopausal women taking the pill had higher S ferritin and a lower frequency of depleted iron reserves than nonusers (p less than 0.01). Postmenopausal estrogen treatment had no influence on S-ferritin or Hb. PMID- 1511066 TI - Biosynthesis of guanidinoacetic acid in isolated renal tubules. AB - Guanidinoacetic acid, a precursor of creatine, is an essential substrate for muscle energy metabolism. Since guanidinoacetic acid has been reported to be synthesized from arginine and glycine by glycine amidinotransferase (transamidinase) in kidney homogenates or slices, the purpose of this study was to provide evidence of guanidinoacetic acid synthesis in isolated tubules from rat kidneys, and to clarify the mechanism regulating it. Isolated rat tubules were incubated with various substrates. Guanidinoacetic acid was separated by high performance liquid chromatography and measured fluorometrically. Results obtained were as follows: (1) Guanidinoacetic acid was synthesized from arginine or canavanine and glycine in isolated rat tubules. (2) D,L-Norvaline, ornithine and methionine suppressed guanidinoacetic acid synthesis. (3) Creatine suppressed guanidinoacetic acid synthesis, i.e. creatine was a negative feedback inhibitor of guanidinoacetic acid synthesis in this in vitro system. (4) Guanidinoacetic acid was not synthesized from hydroxyurea, citrulline, argininosuccinic acid or canaline. These data demonstrate that guanidinoacetic acid is synthesized only from arginine or canavanine and glycine, and that the guanidine cycle may not function fully in the rat renal tubule. PMID- 1511067 TI - Comparison of the properties of ribonucleases in human liver tissue and serum. AB - Two ribonucleases (RNases) with acidic pH optima were partially purified, one from normal human liver tissue and the other from serum. The properties of the two enzymes were studied and compared. Liver RNase was partially purified about 700-fold by acid fractionation, phosphocellulose column chromatography, Sephadex G-75 gel filtration, and polyguanylate affinity column chromatography. Serum RNase was purified about 1200-fold by phosphocellulose column chromatography and Sephadex G-75 gel filtration. The two RNases showed a similar optimal pH and molecular mass, and similar behaviour towards metal ions, but they differed in their substrate specificity. Liver RNase displayed a higher activity towards polyuridylate (poly(U)) than towards polycytidylate (poly(C)), while serum RNase hydrolysed poly(C) more rapidly than poly(U). These findings suggest that liver RNase is not the primary source of the serum RNase with an acidic pH optimum. PMID- 1511068 TI - Magnetic beads in suspension enable a rapid and sensitive immunodetection of human placental alkaline phosphatase. AB - The kinetics and efficiency of the interaction between placental alkaline phosphatase and a monoclonal antibody (laboratory number 327) were determined by immunoassay using microtitre plates or magnetic beads. While only up to 45% of placental alkaline phosphatase was bound to microwells precoated with this antibody, even after prolonged incubation, no less than 60% and 100% binding were reached using magnetic beads after 1 and 3 h incubations, respectively. High molecular-mass placental alkaline phosphatase and complexed placental alkaline phosphatase forms were also completely bound to magnetic beads in the presence of deoxycholate (up to 9 g/l for serum samples). The assay sensitivity was improved up to 4-fold. In addition, 100% binding of the antigen was achieved during simultaneous incubation of magnetic beads, monoclonal antibody (125 micrograms/l), and placental alkaline phosphatase. This one-step enzymatic assay, based on magnetic beads, is an attractive alternative to the classic assay performed in microtitre plates, enabling rapid, precise, and sensitive antigen detection, and only necessitating a minimum of laboratory equipment. PMID- 1511069 TI - Stability of blood gases, electrolytes and haemoglobin in heparinized whole blood samples: influence of the type of syringe. AB - The alterations of blood gases, pH, electrolytes and haemoglobin during 45 min storage in ice-water were measured in 6 types of syringes (1 glass and 5 plastic syringes, among these 3 "blood gas samplers"). It was confirmed that pO2 generally is not stable in plastic syringes. However, considerable differences among plastic syringes were found in this respect, the smallest increase occurring in an ordinary 2 ml syringe for injections and the greatest in one of the special blood gas samplers. Due to the "buffering effect" of deoxyhaemoglobin, the alterations of pO2 are smaller in the hypoxaemic than in the normoxaemic range. Relevant pO2 alterations in plastic syringes are demonstrable after 20 minutes. It is concluded that blood collected in plastic syringes must be analysed within 15 min after sampling, otherwise glass syringes should be used for blood collection. Deviations of pCO2, pH and electrolytes are described in detail. In general, they are due to sampling rather than to storage, and can be effectively minimized by a small dead space of the syringe and by use of an electrolyte-balanced heparin solution. The danger of erroneous haemoglobin measurements due to unequal resuspension of the red cells after storage is pointed out. PMID- 1511070 TI - Performance characteristics of creatine kinase-MB isoenzyme measured with an immunoenzymometric and an immunoinhibition assay in acute myocardial infarction with and without thrombolytic therapy. AB - In a time study we compared the analytical and clinical performance of the Tandem Icon QSR CK-MB enzyme-immunoassay (Hybritech) (creatine kinase-MB) and a creatine kinase-MB immunoinhibition method (Boehringer Mannheim GmbH) (creatine kinase-B). Two hundred and ninety-nine serum samples from 38 patients suspected of acute myocardial infarction were collected at regular intervals during 48 hours. Twenty nine patients were diagnosed as having acute myocardial infarction, of whom 19 received thrombolytic therapy. Although highly correlated, the large scatter around the regression line at low values indicated a different clinical performance of the two methods. We evaluated and compared test performance at different decision levels by means of frequency distributions and predictive values of positive and negative results. For early diagnosis of acute myocardial infarction (4 hours after onset of pain) the Hybritech creatine kinase-MB method gives acceptable predictive values. In thrombolytic treated acute myocardial infarction patients, the peak creatine kinase-MB and creatine kinase-B concentrations were reached after 13.0 h and 13.6 h after the onset of pain, compared with 19.8 h and 17.8 h for patients without thrombolytic therapy. PMID- 1511071 TI - Determination of lipid hydroperoxides in serum iodometry and high performance liquid chromatography compared. AB - It is postulated that lipid peroxidation plays a role in the pathogenesis of a variety of diseases. Efforts have therefore been made to develop reliable and practicable procedures for quantifying lipid peroxidation products such as lipid hydroperoxides in biological specimens. An iodometric cholesterol colour reagent (Merck, Darmstadt, Germany) can be used to measure lipid hydroperoxides in isolated low density lipoproteins without lipid extraction. This method has been validated with respect to its analytical performance and suitability for serum samples by comparing it with a high performance liquid chromatography technique. The method was found to have acceptable performance characteristics with aqueous fatty acid hydroperoxide solutions (linoleic acid) and isolated low density lipoproteins, but it cannot be applied to native serum samples without extraction of lipids. PMID- 1511072 TI - Temperature-dependent matrix effect in the direct enzymatic measurement of blood glucose. AB - The influence of the high-molecular-mass sample matrix in the direct enzymatic measurement of glucose in haemolysate was investigated by a comparison study using ultrafiltered haemolysate for reference. Haemolysate was obtained by 1:21 dilution of whole blood with a solution of digitonin and maleinimide. It was shown that at low protein concentration glucose distributes in a 1:1 ratio during ultrafiltration. With a hexokinase/glucose-6-phosphate dehydrogenase procedure excellent agreement was found between values measured in haemolysate (y) and ultrafiltrates (x), when incubation was performed at 25 degrees C (a = 0.047 mmol/l; b = 0.99; r = 0.999, n = 37); at 37 degrees C, however, the same procedure resulted in a non-tolerable systematic deviation in the direct analysis of haemolysate (a = -0.426 mmol/l; b = 1.00, r = 0.997, n = 37). The precision of measurements in haemolysate and ultrafiltrate was similar (CV 1.0-1.2%). Since stable reference material with an appropriate matrix is not available, it is important to evaluate haemolysate procedures carefully by comparison studies with patient samples. For reduction of experimental error in such studies we recommend the use of ultrafiltered haemolysate, since this can be analysed side by side with haemolysate in the same run. PMID- 1511073 TI - Decreased serum homocysteine in pregnancy. AB - Total serum homocysteine was found to be significantly decreased in the first trimester of pregnancy, became maximal in the second trimester (about 50% compared with non-pregnant women), whereafter the concentration remained stable throughout the remainder of pregnancy. A return to normal concentrations was seen within 2-4 days post partum. Possible reasons for the decrease of serum homocysteine in pregnancy could be haemodilution and increased remethylation of homocysteine due to increased demands for methionine by the foetus. PMID- 1511074 TI - Spectral analysis of EEG during self-paced movements: differences between untreated schizophrenics and normal controls. AB - Thirteen untreated schizophrenic patients, among them nine who had never been treated, were compared with a corresponding number of matched normal controls with regard to changes of the spectral composition of the electroencephalogram (EEG) accompanying voluntary movements. Triggered by self-paced movements of the right fingers (fast fist closure), the spectral composition of three epochs was analyzed: (1) rest (2,5-1,5 sec before movement), (2) movement preparation (last sec before movement onset), and (3) movement execution (1st sec following movement onset). For frequencies above 6 Hz, marked differences between schizophrenics and controls were evident, in particular over the parietal electrodes. Whereas patients exhibited a clear decrease of power density during movement as compared to rest, controls showed only a small decrease (left and mid parietal) or virtually none (only right parietal). Consequently there were significant differences over the right parietal area (P4) between patients and controls in the theta, alpha- and beta-bands with regard to the mean power density and center frequencies of these bands. Also at parietal positions, schizophrenics lacked the enhancement of theta-power during the preparatory epoch that was characteristic for normal controls at all parietal positions. The results are discussed with regard to the well-known disturbances of voluntary motor behavior in schizophrenia. PMID- 1511075 TI - Basal sympathoadrenal function in posttraumatic distress disorder. AB - Research has consistently shown that patients with posttraumatic stress disorder (PTSD) manifest greater changes in heart rate, blood pressure, and plasma epinephrine than controls when exposed to trauma-related laboratory stressors. However, findings are equivocal as to whether PTSD subjects differ from controls on basal, or tonic, measures of autonomic activity. In this study, PTSD patients (n = 11) and asymptomatic controls (n = 11) were compared on measures of basal sympathoadrenal function, including plasma norepinephrine and epinephrine as well as heart rate and blood pressure. Results showed that PTSD patients were not significantly different from control subjects on any measure. Although phasic alterations in autonomic function in PTSD have been consistently found in previous research, this study suggests that tonic sympathetic nervous system activity in PTSD patients may not differ from that of healthy controls. PMID- 1511076 TI - Hypersomnia and morning light therapy for winter depression. PMID- 1511077 TI - P300, clinical symptoms, and neuropsychological parameters in acute and remitted schizophrenia: a preliminary report. PMID- 1511078 TI - Nefazodone--a novel antidepressant--may increase REM sleep. PMID- 1511079 TI - Plasma norepinephrine after a standardized test meal in acute and remitted patients with anorexia nervosa and in healthy controls. PMID- 1511080 TI - Effect of clomipramine and lithium on fenfluramine-induced hormone release in major depression. AB - Prolactin (PRL) and cortisol responses to oral administration of d-1 fenfluramine hydrochloride (60 mg) and placebo were examined in patients with endogenous major depressive disorder on three separate occasions: prior to treatment with clomipramine (CMI), after 4 weeks of CMI administration (175-250) mg/day), and 3 weeks after addition of lithium (Li) carbonate (serum level 0.5-0.9 mmol) to the treatment regimen. CMI significantly increased baseline PRL levels which were further elevated following Li supplementation. PRL response to fenfluramine (minus elevated baseline PRL levels) but not to placebo, was significantly increased by CMI administration, reflected over the 6-hr time course examined and in peak minus baseline values. Following addition of Li, the degree of enhancement was diminished although the peak minus baseline value remained significant relative to the pretreatment response. Cortisol levels were not increased by fenfluramine and were not altered by CMI or CMI + Li administration. The effect of CMI extends previous observations regarding the action of antidepressant treatment on serotenergically mediated hormone release. Methodological considerations relevant to the effect of CMI + Li are discussed. PMID- 1511081 TI - Panic, suicide, and agitation: independent correlates of the TSH response to TRH in depression. AB - We investigated the relationship between suicidality, agitation, panic attacks, and the thyrotropin-stimulating hormone (TSH) response to thyrotropin-releasing hormone (TRH), and tested the hypothesis that panic would account for the association between a reduced TSH response and the other conditions. Twenty-seven euthyroid primary unipolar depressed inpatient women received a TRH test and systematic psychiatric assessment. Panic attacks were insufficient to explain the link between the TSH response and suicidal intent, lethality, and agitation; each condition was independently associated with a lower TSH response. In an additive fashion, copresence of conditions further reduced TSH response. The symptom constellation of panic, agitation, and suicidality in depression may correlate with the greatest reduction in TSH response. PMID- 1511082 TI - Chaotic dynamics in autonomic nervous system activity of a patient during a psychotherapy session. AB - Chaos theory and nonlinear dynamical modeling have been applied successfully in a variety of scientific fields ranging from the physical sciences to population biology. More recently, investigators have modeled long-term psychological processes by applying this paradigm to subjective measures. Yet, mathematically rigorous dynamical modeling of transient psychodynamic processes remains uncharted. Human behaviors and intrapsychic processes often defy prediction, yet psychodynamic theory views these as fundamentally deterministic. We postulate that a nonlinear dynamical analysis of mental states and mental control processes may help reconcile the paradox that seemingly random mental states are thought ultimately to result from deterministic, rather than stochastic, psychological processes. As an initial empirical approach, we examined spontaneously occurring autonomic activity of a patient during 1 hr of psychotherapy and illustrate that cardiac responses associated with psychologically meaningful events possess nonlinear characteristics indicative of chaos. Such nonlinear analyses may shed light on fundamental issues of psychological functioning. PMID- 1511083 TI - Effects of human chorionic gonadotropin and progesterone administration on porphyrin biosynthesis and histology of the Harderian glands in male and female Syrian hamsters. AB - We investigated the influence of hCG and progesterone on the control of porphyrin biosynthesis and histology in the Syrian hamster Harderian glands. Castration of male hamsters caused a marked elevation in porphyrin biosynthesis as revealed by the concentrations of porphyrins and the mRNA levels of the porphyrin pathway rate-limiting enzyme, 5-aminolevulinate synthase (ALV-S). Injection of hCG into castrated male hamsters also resulted in a significant increase in both porphyrin concentrations and levels of ALV-S mRNA compared with those in saline-injected castrated hamsters. Type II cells, which are filled with large lipid vacuoles and are characteristic of male phenotype, disappeared after castration, but administration of hCG partially prevented this change. On the other hand, neither administration of hCG nor progesterone implants could increase the very high porphyrin concentrations and ALV-S mRNA levels characteristic of female Syrian hamsters. As in the case of castrated male hamsters, injections of 20 IU hCG to female Syrian hamsters increased the relative number of Type II cells per square millimeter, whereas progesterone administration did not modify the relative number of Type II cells. These results indicate that hCG can modify Harderian gland morphology in both male and female hamsters and can exert a positive control in the expression of ALV-S gene in castrated male hamsters. PMID- 1511084 TI - Localization and synthesis of entactin in seminiferous tubules of the mouse. AB - Localization and synthesis of entactin in seminiferous tubules of mouse testis was studied by immunocytochemistry. Frozen sections from adult mice testes were subjected to anti-entactin and anti-laminin immunofluorescence. Both entactin and laminin were localized within the seminiferous tubule basement membrane and intertubular region of the testis. The addition of excess amount of entactin (but not fibronectin), premixed with anti-entactin antiserum, abolished the immunostain. Western blotting showed that a protein extract from a seminiferous tubule basement membrane preparation was recognized by anti-entactin anti-serum and comigrated with recombinant entactin. Enriched fractions of isolated primary Sertoli cells and peritubular myoid cells cultured for 6 days on a glass coverslip were able to synthesize and secrete entactin as detected by immunofluorescence microscopy. Entactin was also produced by TM3 (Leydig-like) and TM4 (Sertoli-like) cell lines as detected by both immunofluorescence and Western blotting. The distribution of entactin vs. laminin within both the cultured primary cells and the TM3 and TM4 cell lines differed. Entactin appeared mainly localized extracellularly. In contrast, laminin was mainly localized intracellularly. The above findings suggested that 1) entactin existed in the seminiferous tubule basement membrane and intertubular region of adult mice testis, co-localized with laminin; 2) entactin was synthesized by the cultured primary Sertoli cells and peritubular myoid cells and the TM3 and TM4 cell lines; 3) entactin was exocytosed with little intracellular accumulation, in contrast to an intracellular accumulation of laminin. PMID- 1511086 TI - Immunological identification of G protein alpha- and beta-subunits in tail membranes of bovine spermatozoa. AB - Heterotrimeric G proteins are believed to play important roles as signal transducing components in various mammalian sperm functions. To assess the distribution of G proteins in bovine sperm tails, we purified membranes by hypoosmotic swelling of bovine spermatozoa followed by disruption of plasma membranes in a homogenizer and various centrifugation steps. Electron microscopy revealed highly purified membranes of bovine sperm tails. Subsequently, antisera against synthetic peptides were used to identify G proteins in immunoblots. An antiserum directed against the C-terminal decapeptide of Gi3 and detecting all known pertussis toxin-sensitive alpha-subunits, reacted specifically with a 40 kDa protein. In contrast, various other specific peptide antisera against alpha subunits did not detect any G protein in enriched tail membranes. An antiserum recognizing the beta 2-subunit of G proteins and an antiserum reacting with both beta 1- and beta 2-subunits identified a 35-kDa protein in sperm tail membranes. In contrast, antisera against the 36-kDa beta 1-subunit did not detect any relevant proteins in the membrane fraction. Neither G protein alpha-subunits nor G protein beta-subunits were found in the cytosol. Our results suggest that G proteins in membranes of tails of bovine spermatozoa most likely belong to a novel subtype of G protein alpha-subunits, whereas the putative beta-subunit could be identified as a beta 2-subunit. PMID- 1511085 TI - Synthesis of uterine endometrial proteins during early diestrus in the cyclic and pregnant dog, and after estrogen and progesterone treatment. AB - The objectives of this study were to identify and characterize dog uterine endometrial proteins synthesized de novo in explant culture during early luteal phase, to examine distribution of these proteins prior to the embryo's entering the uterus and during its free-floating period prior to implantation, and to examine regulation of endometrial proteins by estrogen and progesterone (P4) treatments. Uterine endometrium was collected from cyclic and pregnant bitches on diestrus Days 3, 7, and 10 as determined by loss of cornification of vaginal epithelium, and from ovariectomized dogs after treatment with corn oil, estrogen, P4, or estrogen followed by 1 or 2 wk of P4. Tissue was incubated in an explant culture system in the presence of [3H]leucine or [35S]methionine. The rate of incorporation of [3H]leucine into nondialyzable macromolecules indicated no significant change in rates of incorporation by status (pregnant vs. nonpregnant), day, or steroid treatment. Uterine endometrial-conditioned culture medium, analyzed by two-dimensional SDS-PAGE and fluorography, revealed a complex array of at least ten proteins or protein complexes in cyclic and pregnant bitches. No difference in protein pattern was detected by status; however, differences in distribution were apparent by day of cycle or early pregnancy. Two major proteins, cP5 (M(r) 54,686) and cP6 (M(r) 23,010) appeared to be differentially expressed. Expression of cP5, maximal on diestrus Day 3, decreased as the cycle or pregnancy progressed to diestrus Day 10. In contrast, expression of cP6, a minor protein on diestrus Day 3, appeared to be up-regulated for each status to Day 10, with increased intensity and multiple isoelectric and molecular weight variants. In ovariectomized steroid-treated dogs, two-dimensional SDS-PAGE showed that pattern and distribution of specific proteins were affected by treatment. Acidic protein cP1 (M(r) 87,600), synthesized after corn oil and P4 treatment, was suppressed with estradiol (E2). Proteins cP2 (M(r) 40,000 and M(r) 42,000), present with all treatments, were intensified with P4. A high-M(r) basic protein complex (cP3) and acidic protein cP4 were expressed with E2 and maintained with P4 treatment. Proteins cP5 and cP6, while not induced by E2 or P4 alone, required E2 priming for P4 induction. Protein cP5 was down-regulated while cP6 was up-regulated with P4 for 2 wk. Proteins induced by estrogen followed by 1 or 2 wk of P4 treatments were similar to those released by endometrial explants collected from pregnant and cyclic bitches on Days 3, 7, and 10 of spontaneous diestrus.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1511087 TI - Production of chimeric hamsters by aggregation of eight-cell embryos. AB - Chimeric animals were produced by aggregation of 8-cell-stage embryos from two strains of hamsters (LVG and Bio 1.5). Two series of experiments were performed. In the first series, embryo pairs in contact with each other were classified as aggregates even if 2 distinct embryos could still be distinguished. Of 88 aggregates transferred, 2 chimeras were obtained. Pregnancy rate was 25%, and embryo survival was 35%. In the second set of experiments, only embryo pairs that had coalesced to form a single giant blastocyst were classified as aggregates. Of 56 aggregates transferred, 6 chimeras were obtained. Pregnancy rate was 83%, and embryo survival was 30%. Of the 8 chimeras, 6 were phenotypic males, and 2 were phenotypic females. Both females were germ line chimeras. Of the 6 males, 4 reproduced normally, 1 had abnormal external genitalia but normal spermatogenesis, and 1 was sterile and had atrophic testes. Each of the fertile males transmitted only a single component, either the LVG or the Bio 1.5. Examination of the testes from the sterile chimera revealed that in excess of 80% of the seminiferous cords were devoid of germ cells. These results demonstrate that hamster chimeras can be obtained by aggregation of 8-cell-stage embryos. PMID- 1511088 TI - Gonadotropin surge increases fluorescent-tagged low-density lipoprotein uptake by macaque granulosa cells from preovulatory follicles. AB - In the primate ovary, luteal steroidogenesis is largely dependent upon cholesterol derived from receptor-mediated uptake of circulating low-density lipoprotein (LDL). However, granulosa cells (GC) of preovulatory follicles possess few LDL binding sites compared to those present in developing and mature corpora lutea. We recently reported (Endocrinology 1991; 129:3247-3253) that uptake of LDL tagged with the fluorescent probe 1,1'-dioctadecyl-3,3,3',3' tetramethyl-indocarbocyanine perchlorate (DiI) can be monitored in macaque luteal cells by fluorescence-activated flow cytometry. This study was designed to determine whether an ovulatory stimulus induced uptake of DiI-LDL in GC aspirated from preovulatory follicles of macaques undergoing ovarian stimulation. Development of multiple large follicles was stimulated in adult rhesus macaques with human gonadotropin treatment for 9 days. On Day 10, monkeys received either no ovulatory stimulus or 1000 IU hCG to initiate ovulatory events. GC were aspirated on Day 10 in monkeys receiving no ovulatory stimulus (nonluteinized GC) or 27 h or 34 h after hCG injection (luteinizing GC). GC were resuspended in Ham's F-10 medium + 0.1% BSA and incubated with several concentrations (0-25 micrograms/ml) of DiI-LDL (Biomedical Technologies, Stoughton, MA) for various time intervals (2-60 min). DiI-LDL uptake by GC was time- and concentration dependent. Coincubation of cells with DiI-LDL and unlabeled LDL dose-dependently suppressed the percentage of fluorescent cells. In contrast, coincubation with up to a 250-fold excess of acetylated LDL or high-density lipoprotein did not alter the percentage of fluorescent GC.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1511089 TI - Active and passive immunoneutralization of inhibin increases follicle-stimulating hormone levels and ovulation rate in ewes. AB - Two experiments were conducted to determine effects of active and passive immunoneutralization of inhibin on FSH secretion and ovulation rate. A synthetic peptide (alpha-IF) matching the N-terminus of the alpha-subunit of ovine inhibin was coupled to human alpha-globulin (h alpha-G) and used as an immunogen. In experiment 1, estrus was synchronized in 10 sheep that had been actively immunized against alpha-IF-h alpha-G or h alpha-G. Plasma FSH levels were similar in the two groups of ewes at -52 and -48 h (0 h = onset of estrus). In alpha-IF-h alpha-G-immunized ewes, FSH increased from -48 to -44 h (18.8-22.1 ng/ml), and then fell to 16.2 ng/ml by 0 h. In h alpha-G-immunized ewes, FSH decreased from 48 to 0 h (17.6-7.2 ng/ml). Ovulation rate was higher in alpha-IF-h alpha-G- than h alpha-G-immunized ewes (9.4 vs. 2.4). In experiment 2, antibodies (Ab) were extracted from sera obtained from experiment 1 ewes and then were injected i.v. into 12 other ewes. Estrus was synchronized twice during the breeding season using progesterone-releasing pessaries (CIDR-G). One day before CIDR-G withdrawal, alpha-IF-h alpha-G and h alpha-G Ab were administered in a crossover design. After injection of Ab against alpha-IF-h alpha-G, plasma FSH increased from 0 to 24 h post-injection (10.9-21.5 ng/ml), after which levels fell to 14.2 ng/ml by onset of the preovulatory LH surge.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1511090 TI - Decreased luteinizing hormone-stimulated progesterone secretion by preovulatory follicles isolated from cyclic rats treated with the progesterone antagonist RU486. AB - Since administration of the antiprogesterone RU486 to cyclic female rats at metestrus and diestrus results in increased serum levels of LH, estradiol, and testosterone at proestrus, we investigated whether RU486 affects follicular steroidogenesis. Female rats with a 4-day estrous cycle, induced experimentally by a single injection of bromocriptine on the morning of estrus, were given RU486 (2 mg) twice daily (0900 and 1700 h) on metestrus and diestrus. At proestrus the preovulatory follicles were isolated and incubated for 4 h in the absence and presence of LH. In the absence of LH, accumulation of estradiol, testosterone, and progesterone in the medium was not different for RU486-treated rats and oil treated controls. In contrast, LH-stimulated estradiol, testosterone, and progesterone secretions were significantly lower in RU486-treated rats compared with controls. Addition of pregnenolone to the incubation medium resulted in a significantly lower increase of progesterone in follicles from RU486-treated rats compared with those from oil-treated controls. This suggests that 3 beta hydroxysteroid dehydrogenase (3 beta-HSD) activity is decreased by administration of RU486 in vivo. Aromatase and 17 alpha-hydroxylase/C17-20 lyase activities were not affected: addition of substrate (androstenedione and progesterone respectively) did not affect differently the amount of product formed (estradiol and testosterone) in RU486- and oil-treated rats. However, LH-stimulated pregnenolone secretion was lower in follicles from RU486-treated rats compared with follicles from oil-treated controls, suggesting that either cholesterol side chain cleavage activity or LH responsiveness is decreased. At proestrus the preovulatory follicles from RU486- and oil-treated rats were not morphologically different.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1511091 TI - Expression of bovine trophoblast interferon in conceptuses derived by in vitro techniques. AB - Expression of the trophoblast interferon, bovine trophoblast protein-1 (bTP-1), has been studied in embryos produced by in vitro maturation-in vitro fertilization (IVM-IVF). No bTP-1 production was noted until after embryos had reached the expanded blastocyst stage and had begun to hatch (Days 8-9 post fertilization). Single blastocysts comprising 115 +/- 22 cells released 1.0 +/- 0.1 units of interferon activity/24 h. Amplification of conceptus mRNA by reverse transcription-polymerase chain reaction procedure with bTP-1-specific oligonucleotides confirmed that bTP-1 transcripts were present in blastocysts but were not detectable at earlier stages. Although cultured blastocysts produced by IVM-IVF procedures continued to secrete bTP-1 for a few days, they failed to attach to the substratum and form outgrowths, and soon lost structural integrity. However, when Day 8 blastocysts/morulae were transferred to the uteri of synchronized cows, recovered 4 days later, and placed into individual cultures, they attached and formed outgrowths that produced large amounts of bTP-1 (greater than 2000 units/culture/24 h after 14 days). Embryos thus first expressed bTP-1 when a functional trophectoderm was first formed, and induction did not require a period of in vivo development. However, continued viability of the blastocyst and bTP-1 production were not sustained in vitro and may require some exposure to the uterine environment. PMID- 1511092 TI - Beta-nerve growth factor influences the expression of androgen-binding protein messenger ribonucleic acid in the rat testis. AB - The effect of infusion of nerve growth factor (NGF) into the rat testis on the expression of androgen-binding protein (ABP) mRNA was studied. A major 1.7-kb and a minor 3.7-kb ABP mRNA were present at all stages of the seminiferous epithelium with maximal levels at stages VIII-XI and the lowest levels at stages IV-VI. Infusion of 15 ng/h of NGF with a mini-osmotic pump for 14 days resulted in a 2 fold increase of ABP mRNA as revealed by Northern blots, whereas the mRNA level of another Sertoli cell protein, urokinase-type plasminogen activator, remained unchanged. Image analysis of autoradiograms obtained by in situ hybridization of sections from treated testes showed a similar increase in APB mRNA compared to noninfused or PBS-infused testes. However, at the cellular level the labeling intensity for ABP mRNA over Sertoli cells of different stages of the seminiferous epithelium was the same in NGF-infused and control testes. This suggests that the increase of ABP mRNA in NGF-infused testes was caused by prolongation of stages VII-VIII with maximal ABP mRNA expression; the suggestion is supported by an increase of 30 percent in frequency of these stages in histological sections from NGF-infused testes. PMID- 1511093 TI - Prenatal androgens and the timing of seasonal reproductive transitions in sheep. AB - Both the onset of puberty in the lamb and the annual resumption of reproductive activity in adult male and female sheep are characterized by increased secretion of LH due to reduced responsiveness to steroid inhibition. However, the timing of puberty is sexually differentiated, for males undergo a reduction in sensitivity to steroid feedback at 10 wk of age, whereas females remain highly responsive to steroid inhibition until 30 wk. This sex difference is determined by androgens in utero. The present study was conducted to determine whether a sex difference exists in the timing of seasonal transitions in adult males and females. We compared serum LH in gonadectomized, estradiol-treated males (n = 7), females (n = 6), and androgenized females (n = 5) from blood samples collected twice weekly for one year. As determined by changes in the pattern of LH secretion, the onset and termination of the autumn breeding season were not different between males, females, and androgenized females (termination: 1 February +/- 4 days, mean +/- SE all groups; onset: males, 22 August +/- 4 days; females, 5 September +/- 18 days; androgenized females, 16 September +/- 10.5 days). However, there was a transient increase in LH (20 May to 23 June) in males, but not in females or androgenized females. Although no effects of prenatal testosterone were evident in the control of LH secretion in adult androgenized females, LH secretion in androgenized males was elevated throughout the nonbreeding season in 3 of 5 animals, indicating that exogenous testosterone may reduce seasonal increases in responsiveness to steroid inhibition.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1511094 TI - The effect of estrogen and progesterone on structural changes in the uterine glandular epithelium of the ovariectomized sheep. AB - The development of epithelial cells of the uterine glands of ovariectomized sheep in response to estradiol-17 beta (E) and progesterone (P) was studied using light and electron microscopy. Animals that had been ovariectomized for six weeks were placed in one of three experimental treatment groups. Group I animals (untreated controls) received no steroid treatment. Group II animals (E alone) received one 4-cm E implant (E approximately 5-10 pg/ml) and their uteri were removed after 2, 4, or 6 days. Group III animals (E-primed, P-treated) received an E implant (E approximately 5-10 pg/ml) for 6 days and then were treated with six 13-cm P implants (P approximately 1.5-3 ng/ml), in the continued presence of E, for 2, 4 or 6 days. Six weeks after ovariectomy the epithelial cells of the uterine glands were low cuboidal and morphologically appeared to be synthetically inactive. Following 2 days of E treatment the epithelial cells had significantly increased in cell height, and protein-synthesizing organelles were well developed. Maturation of the secretory apparatus continued throughout E treatment. The Golgi complex and rough endoplasmic reticulum (RER) were abundant. Lysosomal-like granules and granules of varying electron density were present in the cytoplasm. The chronic administration of P to E-primed animals did not result in any further increase in cell height. Elongated mitochondria, a cup-shaped Golgi apparatus, extensive apical microvilli, and irregularly shaped membranous profiles in the supranuclear cytoplasm characterized these uterine epithelial cells. Lysosomal like granules, small vesicles, and scattered patches of glycogen were seen in the cytoplasm. These data show that the uterine epithelial cells of the ovariectomized sheep undergo morphological alterations in protein-synthesizing organelles and apical specializations that depend on the presence of E and P. PMID- 1511095 TI - A two-receptor model for salmon gonadotropins (GTH I and GTH II). AB - The possible existence of distinct receptors for salmon gonadotropins (GTH I and GTH II) and the distribution of the receptor(s) were studied through examination of the binding of coho salmon (Oncorhynchus kistuch) GTH I and GTH II to membranes from thecal layers and granulosa cells of salmon ovaries. Purified coho salmon gonadotropins were iodinated by the lactoperoxidase method. Crude membrane preparations were obtained from thecal layers, granulosa cells, and whole ovaries of coho salmon in the postvitellogenic/preovulatory phase. Binding of 125I-GTH I to membranes from thecal layers, granulosa cells, and whole ovaries, and binding of 125I-GTH II to thecal layer cell membranes could be inhibited by both GTHs, but GTH I was more potent than GTH II. In contrast, GTH II was more potent than GTH I in inhibiting 125I-GTH II binding to membranes from granulosa cells and whole ovaries, but the inhibition curves were not parallel. Scatchard plot analysis suggested that there was a single type of receptor in the thecal layers for both GTHs, whereas in the granulosa cells there was more than one type of receptor for both GTHs. Based on these results, a two-receptor model for the postvitellogenic/preovulatory salmon ovary is proposed with the following features: 1) there are two types of gonadotropin receptors in the salmon ovary, type I and type II; 2) the type I receptor binds both GTHs, but with higher affinity for GTH I, whereas the type II receptor is highly specific for GTH II and may have only limited interaction with GTH I; and 3) the type I receptor is present in both thecal cells and granulosa cells, whereas the type II receptor is present in granulosa cells. PMID- 1511096 TI - Regulation of proto-oncogene expression and deoxyribonucleic acid synthesis in granulosa cells of perifused immature rat ovaries. AB - The present series of experiments examined the effects of follicle-stimulating hormone (FSH) and insulin (IN) on granulosa cell (GC) proto-oncogene expression and DNA synthesis. In the first study, GCs were harvested from immature rat ovaries after 15, 30, or 60 min of perifusion and DNA synthesis (3H-thymidine incorporation) and proto-oncogene mRNA levels were determined. The presence of c myc and c-fos proteins was localized within GCs immunocytochemically. GCs of control ovaries exhibited modest levels of DNA synthesis and proto-oncogene expression. FSH/IN not only stimulated DNA synthesis but also increased c-myc, c fos, and c-jun mRNA levels and the percentage of cells staining for c-fos and c myc proteins. The protein kinase inhibitor, 2-aminopurine (2-AP), inhibited the FSH/IN-induced increases in c-myc and c-fos mRNA levels, the percentage of cells staining for Myc and Fos protein, and DNA and protein synthesis. The effects of 48 h of perifusion with FSH in the presence or absence of IN were also examined. These treatments were selected because after 48 h of continuous exposure to FSH alone, estradiol-17 beta (E2) secretion is enhanced and 3H-thymidine incorporation is inhibited. Conversely, FSH/IN maintains 3H-thymidine incorporation for up to 48 h of perifusion culture without stimulating E2 (Peluso et al., Endocrinology 1991; 128:191-196). After 48 h of perifusion, both FSH and FSH/IN stimulated c-fos mRNA and protein levels. However, high levels of c-jun mRNA and protein were detected only within GCs of FSH/IN-treated ovaries.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1511097 TI - Effect of 48-hour infusion of the synthetic oxytocin antagonist, [1-beta mercapto(beta-(CH2)5)1(OMe)Tyr2,Orn8]-oxytocin, on myometrial activity of pregnant sheep at 139-140 days of gestation. AB - Currently there is considerable interest in the actions of oxytocin antagonists on the pregnant myometrium. Few studies have been conducted involving long-term infusions of oxytocin antagonists to late-pregnant experimental animals. We set out to determine whether continuous infusion of an oxytocin antagonist ([1-beta mercapto(beta-(CH2)5)1(OMe)Tyr2,Orn8]-oxytocin) would influence basal levels of myometrial activity of the contracture type and maternal prostaglandins in pregnant sheep. The antagonist was infused into a uterine vein at 80 micrograms.h 1 for 48 h starting at 139 days of gestational age. The antagonist significantly reduced total myometrial electromyogram activity and the frequency of contractures but did not change contracture duration. Antagonist infusion did not produce any significant alterations in maternal carotid or uterine vein 13,14 dihydro-15 keto prostaglandin F2 alpha concentrations. Contractures probably represent an intrinsic instability of the resting membrane potential of uterine muscle and these results suggest that oxytocin may play a role in regulating their frequency in sheep during the last third of gestation. PMID- 1511098 TI - The perinuclear matrix as a structural element of the mouse sperm nucleus. AB - The mouse sperm nucleus, after the removal of protamines and DNA, consisted of a skeletal structure that conformed to the original nuclear shape. Sperm were extracted with 1% SDS, and the isolated nuclei, along with the enveloping perinuclear theca, were incubated in 25 mM dithiothreitol, and exposed to different reagents in an effort to displace the protamines, P1 and P2. Protamines, labeled with [3H]arginine, were displaced from the nucleus by CaCl2.MgCl2, but only partially by anionic detergents, monovalent cations, and polyvalent anions. Displacement of P1 and P2 was achieved by digesting the nuclei with DNase I and simultaneously extracting with CaCl2.MgCl2 (3:2; mol:mol) in stepwise increments of 125, 150, 175, 200, and 250 mM. Protamine displacement was concentration-dependent, occurring with an EC50 of approximately 205 mM and with maximal displacement at approximately 250 mM CaCl2.MgCl2. The nucleus was reduced to a skeletal structure consisting of the perinuclear theca and an internal network of transverse fibers. The evidence was consistent with the former being derived from the perforatorium and postacrosomal nuclear sheath (both cytoplasmic structures), whereas the fibers were most likely of nuclear origin. By SDS-PAGE and isoelectric focusing (IEF), perinuclear matrices consisted of greater than or equal to 230 protein spots, with M(r)s in the range of 70,000 to 8000 and pIs of greater than or equal to 7.5 to approximately 4.7, respectively. Monoclonal antibodies prepared against perinuclear matrices bound to specific proteins on IEF immunoblots and, based on light and electron microscopic observations, to discrete domains of the sperm perinuclear theca and nucleus. PMID- 1511099 TI - Heterogeneity of cell populations that contribute to the formation of primordial follicles in rats. AB - To study the events that lead to the formation of primordial follicles, pregnant rats were given continuous infusions of [3H]thymidine (3H-TdR) beginning on Days 14-19 of pregnancy (e14-e19) and continuing for 48-120 h. Ovaries from the pups were collected and plastic-embedded histological sections were prepared for autoradiography. The autoradiographs revealed that within the core of the developing ovary were a large number of cells that remained mitotically inactive (failed to incorporate label) from e14 through the day of birth. These unlabeled cells gave rise to the granulosa cells of the first follicles that formed, were located in the medulla of the ovary, and were the first to begin growth. The unlabeled cells did not appear to contribute to the formation of the follicles that formed later in the cortical region of the ovary. When 3H-TdR infusion was begun during late pregnancy, a small subset of the germ cells incorporated label, although the vast majority did not. The labeled germ cells are presumed to represent those that were lagging in their development (had not yet entered meiosis). After ovarian histogenesis was completed during the first week postpartum, the unlabeled ocytes were found concentrated in the core of the ovary, enclosed in the earliest growing follicles; labeled oocytes were found exclusively in the cortex of the ovary, within tiny, quiescent primordial follicles. These observations provide some empirical support for long-held, but heretofore untested, hypotheses concerning early folliculogenesis: that the first follicles that begin to grow are qualitatively different from the remaining follicles in the ovary and that primordial follicles begin to grow in the order in which they were first formed. PMID- 1511100 TI - Mating induces puberty in the female musk shrew. AB - Female musk shrews (Suncus murinus), lacking a behavioral estrous cycle, engage in copulatory behavior whenever tested; even during pregnancy, sexual activity can be displayed. Studies suggest that protracted sexual behavior has a functional significance in this species. Virgin females receiving a series of ejaculations over the course of several days are more likely to ovulate and subsequently deliver than animals given the same number of ejaculations over an interval of a few hours. After the virgin mating only one third of the ovaries placed in culture exhibit increased steroidogenesis. In the present set of studies, the hypothesis that the virgin mating induces the onset of puberty, in a manner similar to that in which male-related pheromones induce estrous in rodents, was tested. On the basis of gestational lengths it is evident that females mated three times (on Days 0, 4, and 8) became pregnant in the vast majority of cases as a result of the second and third matings. When the first and second matings were separated by 25 days, 82% of females ovulated in response to the second mating; less than one third of females mated only once ovulated. Finally females were housed across a screen from males, exposed to male urine, or housed alone prior to the virgin mating. In none of these cases did pre-exposure to male-related cues increase ovulation rates in response to the virgin mating. The results show that the virgin mating primes the neuroendocrine system in such a way that the pubertal ovulation can occur in response to subsequent mating.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1511101 TI - Inhibition of pituitary bioactive prolactin secretion in the male rat by the glucocorticoid agonist decadron phosphate. AB - In the present studies, the soluble glucocorticoid agonist, decadron phosphate (DEC), was administered i.v. to intact adult male rats in order to evaluate the effects of glucocorticoid receptor stimulation on circulating levels of immunoreactive (ir-) and bioactive (bio-) prolactin (PRL). In light of reports that glucocorticoid-specific receptors exist within the rat brain, additional experiments investigated the effects of intracerebroventricular (i.c.v.) administration of graded doses of the same drug on pituitary ir- and bioPRL secretion. Concentrations of ir- and bioPRL in samples obtained before and after drug treatments were determined by standard PRL radioimmunoassay and the Nb2 rat node lymphoma bioassay, respectively. Rats injected i.v. with 0.5 mg DEC/kg body weight, but not those treated with a tenfold lesser dose, exhibited decreased plasma irPRL concentrations. However, both doses promoted a decline in circulating levels of bioPRL compared to vehicle-treated controls, along with an overall reduction in the plasma bio/irPRL ratio. The magnitude and duration of this drug-induced decline in biopotency of secreted hormone was dose-dependent. While the plasma bio/irPRL ratio was diminished only transiently in rats injected with 0.05 mg DEC/kg, treatment with the higher dose led to a sustained decrease in the plasma bio/irPRL ratio for the duration of the experiment. The current studies also show that intracerebral administration of DEC resulted in dose dependent alterations in pituitary PRL release. Circulating levels of ir- and bioPRL were not altered in rats injected i.c.v. with 10 ng of DEC, the lowest dose tested.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1511102 TI - Kinetics of follicle growth in the prepubertal gilt. AB - Follicular growth rates were determined by histological examination of ovaries of five prepubertal gilts following treatment with the stathmokinetic agent colchicine. One ovary from each of five gilts was removed surgically and then colchicine (n = 3) or saline (n = 2) was infused i.v. Precisely 2 h after treatment with colchicine, the remaining ovary was removed. Ovaries were processed for histological analyses and sectioned at 10 microns; every twentieth section was stained with hematoxylin and periodic acid-Schiffe's. Sections were viewed with a projection microscope and individual follicles were measured. Eight classes of follicles were established such that the number of granulosa cells per cross section doubled in each class. Diameters of follicles for each class were as follows: 1) less than 106 microns, 2) 106-148 microns, 3) 148-206 microns, 4) 206-287 microns, 5) 287-400 microns, 6) 400-657 microns, 7) 657-1480 microns, and 8) 1480-3130 microns. A layer of thecal cells was first seen in class 2 follicles, and 76% of class 3 follicles had a thecal layer. Oocyte diameter increased through the first four classes and reached a maximum diameter of approximately 110 microns. Almost all follicles greater than 400 microns had an antrum. Preantral follicles had a lower mitotic index and a higher mitotic time and class time than antral follicles. Growth rate increased with increasing size of follicles. Preantral follicles grew at a rate of 5.2 microns/day whereas antral follicles grew at 313 microns/day.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1511103 TI - Localization of c-fos-like proteins in the mouse endometrium during the peri implantation period. AB - Fos, which collectively refers to protein products of the c-fos proto-oncogene family, was immunohistochemically localized in the mouse uterus to ascertain the effects of steroids on Fos expression in the mouse and to determine the course of Fos expression during normal pregnancy and pseudopregnancy. In ovariectomized mice, Fos was induced in luminal and glandular epithelium and an occasional stromal cell following treatment with 100 ng 17 beta-estradiol (E2). Priming with 2 mg progesterone (P4) for 3 days prior to the administration of 100 ng E2 or giving 100 ng E2 and 2 mg P4 concomitantly induced Fos in the luminal and glandular epithelium with enhanced staining in stromal cells. Priming with P4 before giving E2 had the added effect of inducing Fos at an earlier time point. Progesterone alone failed to induce Fos in any cell type in the uteri of ovariectomized animals. On Days 1 and 2 of pregnancy and pseudopregnancy, Fos was detected in the luminal and glandular epithelium and in the stroma. Staining was decreased by Day 3 and was not detectable by the morning of Day 4. No further staining for Fos was found during subsequent days of pseudopregnancy. On the afternoon of Day 4 of pregnancy, Fos was detected in the epithelium and the antimesometrial stroma. On the morning of Day 5, implantation sites and non-site areas were distinguishable, with Fos present in luminal epithelium and antimesometrial stroma in sites, and in just the luminal epithelium in non-sites. Fos remained in the epithelium of non-sites through Day 7 of pregnancy. In sites on the afternoon of Day 5, staining was found in the luminal epithelium and primary decidual zone. On Day 6, staining was found in the secondary decidual zone, but was absent from the primary zone and epithelium. On Day 7, Fos was also detected in the embryonic trophoblast giant cells and the ectoplacental cone. These results demonstrate that E2 and P4 modulate Fos in the mouse endometrium and that Fos is induced during implantation. Significantly, the embryo appears to induce Fos expression on the afternoon of Day 4, while it is still encased in the zona pellucida. PMID- 1511104 TI - [Family dysfunction]. PMID- 1511105 TI - [Physicians' incomes in primary care]. PMID- 1511107 TI - [Maternal health knowledge and its use in pediatrics in primary care]. AB - OBJECTIVE: To find the nature of the relationship between the general level of mothers' health knowledge and the over-use of paediatric facilities at the Primary Care level. DESIGN: A crossover study with a control group. SITE. Zaidin Sur Health Centre (Granada). PATIENTS OR OTHERS PARTICIPANTS: We selected all the over-users (69) of a Paediatric office and compared them to a random sample, grouped by age, of normal users (82); n = 151. MAIN MEASUREMENTS AND RESULTS: To control confusion, we measured a total of 31 variables, grouped as to need, predisposition and expediting factors. After validating the scales, the average scores for general health understanding and the score for clinical attitudes and knowledge were significantly lower in the over-user group (p = 0.017 and p = 0.000). The scale for attitudes to and knowledge of prevention did not attain any importance (p = 0.104). We worked out a model of multiple logistical regression which included in the equation the scale of clinical attitudes and knowledge (p less than 0.005). CONCLUSIONS: We emphasised the importance of mothers' health knowledge to the question of over-use of paediatric facilities. It is desirable to attempt to intervene on this question in order to lessen excessive use of health facilities. PMID- 1511106 TI - [Functional classification of chronic alcoholic hepatopathy in primary care]. AB - OBJECTIVE: To evaluate the use of Pugh's Classification in assessing patients with diffuse alcoholic Chronic Hepatopathy in the out-patient context. DESIGN: Descriptive-retrospective study. SITE. The Base Health Area of "La Mina" in Barcelona. PATIENTS OR OTHER PARTICIPANTS: 143 patients over the age of 14 diagnosed as suffering diffuse chronic Hepatopathy were identified. 37 of these were excluded because of lack of data. MAIN MEASUREMENTS AND RESULTS: The following data were gathered: those relating to semeiology, anamnesis, quantifying alcoholic intake, where the original diagnosis was made, how rapidly the condition evolved, laboratory and complementary explorations' parameters. Out of the 106 patients studied 71 (67%) were classified in group A; 22 (21%) in B and 13 (12%) in C. No significant differences were found in relation to age or sex. Significant differences concerning the speed of the condition's evolution and the average intake in grammes of alcohol per day were observable. The number of hospital admissions increased as the patient's functional stage became worse and complications increased. CONCLUSIONS: Pugh's test was shown to be useful in the out-patient context for classifying patients suffering chronic diffuse Hepatopathy in line with the severity of their condition. PMID- 1511108 TI - [Prospective study of the development of excess weight in a group of chronic ambulatory patients]. AB - OBJECTIVE: To assess the effect of Health Education on excess weight. DESIGN: Observational crossover study in order to analyse the prevalence of excess weight. Prospective study with intervention. SITE. At the Primary Care level (the Vilanova del Cami Health Centre) in a semi-urban district with 9,173 inhabitants. POPULATION: Patients registered with the chronically ill nursing office in one of three General Medical units. Six patients seen at home and 4 how did not attend personally were not counted. The remaining numbered 87, out of which 17 did not present excess weight (the latter being defined as when there is a ratio of body mass (RBM) superior to 25). INTERVENTIONS: For the purpose of the intervention carried out to reduce weight, the 70 obese patients were divided into three groups: no intervention (N), hygienic/dietetic measures (M), and hypocaloric diet (D). MAIN MEASUREMENTS AND RESULTS: The variation of weight and RBM achieved over six months was studied. The parameters for matching data were compared. In group N, a light weight increase of no statistical significance was found. In group M, a highly significant reduction of weight and RBM was observed (p less than 0.001). In group D, weight reduction presented a strong correlation (p less than 0.01) and the reduction in RBM was highly significant (p less than 0.001). CONCLUSIONS: An abstentionist attitude to the problem of excess weight cannot be justified, seeing that notable results can be obtained using hygienic/dietetic measures alone. PMID- 1511109 TI - [Minimum sets of data in primary care: an exploration of their feasibility]. AB - OBJECTIVE: To evaluate the different "costings" of several different strategies for gathering a Minimum Set of Data (MSD) at the Primary Care level. DESIGN: A simulation study using a hypothetical MSD with 16 items together with the findings on demand and interventions made by General Physicians in an observational study in Andorra. Different gathering strategies were applied using these data and with the MSD register covering visits as the starting-point. Measurement of the "costing" or work-load involved in the gathering and transmission of each of the items was carried out by means of a nominal group. SITE. General and paediatric consulting-rooms. PATIENTS OR OTHERS PARTICIPANTS: The simulation was carried out among the catchment population of PAMEM and used data on what was done in 1988. MAIN MEASUREMENTS AND RESULTS: Strategies based on sampling of visits or individuals are those which show a greater reduction in cost (99.3% and 98.1% respectively). Sampling individuals additionally allows for the MSD to be added to during periods of illness. Other options with their respective results are: "gathering information from alternative sources", with a reduction of 22%, "reduction of the number of data to record", with 20% reduction and "separation of stable information" with 18%. CONCLUSIONS: The systematic collection of data on each visit has important and much more efficient alternatives. The choice of one of them will depend on how feasible it is to introduce, on the available resources and above all on objectives. PMID- 1511110 TI - [Chronic pathologies and pharmaceutical expenditure in persons over the age of 65]. AB - OBJECTIVE: For purposes of the present study of people over 65 attending a particular Health Centre, we aimed to discover and inter-relate their morbidity due to chronic illnesses, their frequency of attendance, and the total average outlay of drugs on them. DESIGN: Descriptive crossover study. Information on the clinical histories was gathered over a one-year period (July 1990 to June '91). SITE. Within the Primary Care framework: at the Vite Health Centre in Santiago de Compostela. PATIENTS OR OTHERS PARTICIPANTS: The population aged 65 or over and with medical records in the said centre. A representative sample of this population (n = 240), obtained by systematic sampling, was worked with. MAIN RESULTS: The sample's average age was 73.6 +/- 6.7 years. Arterial Hypertension (AHT) was the most common chronic illness. AHT, LCFA/Asthma, Hyperlipemia and digestive pathology showed significant differences between men and women. The average number of medical consultations per person per year was 11.5 +/- 0.82, with no significant differences as to sex and age. The average outlay per person per year was 27,610 pesetas +/- 38,688, with an average cost per consultation of 2,750 pesetas +/- 5,158.7. The chronic illnesses that produced a higher average total cost were heart diseases. Significant differences were shown between the number of chronic illnesses and the average total cost. CONCLUSIONS: The presence, number and nature of chronic illnesses are the factors affecting higher outlay in medication. PMID- 1511111 TI - [Atypical presentations of primary hypothyroidism in primary care]. AB - OBJECTIVE: To present three cases of primary Hypothyroidism with an atypical beginning. DESIGN: Retrospective clinical observations. SITE. Health Centre (Primary Care). PATIENTS OR OTHERS PARTICIPANTS: Three women (aged 38, 43 and 51) who were studied in the consulting room: one who presented Macrocytosis and Hypercholesterolemia; the second, a bilateral palpebral oedema; and the third, dysfonia unaccompanied by any other symptom of Hypothyroidism. MAIN MEASUREMENTS AND RESULTS: In the three cases, hypercholesterolemia was objectified, I4 diminished and TSH raised; in one of them T3 was normal, while it was low in the remainder. CONCLUSIONS: The alteracions observed are frequent in primary Hypothyroidism. But it is rare to find them on their own in the presentation of the clinical picture. Given this pathology's high prevalence, it is important to think of the pathology when presented with these atypical symptoms, and possibly to request the determination of TSH in isolation. PMID- 1511112 TI - [New antibiotics and primary care]. PMID- 1511113 TI - [Programming and protocol of acute pathologies in primary care]. PMID- 1511114 TI - [The incorporation of a new model in medicine: theoretical and practical consequences]. PMID- 1511115 TI - [Organization of continuing care in health centers]. PMID- 1511116 TI - [Understanding school-children's hygiene habits]. PMID- 1511117 TI - [Concerning the adequacy of demands in function of the seriousness of emergencies]. PMID- 1511118 TI - A study of cervical cancer in Ethiopian women. AB - In common with many African countries, Ethiopia has a very limited cytological service, smears are only taken in a hospital or clinic setting and until very recently most had to be sent abroad for analysis. We describe the results of a clinical and cytological investigation of 2111 women attending hospitals and clinics in Addis Ababa: 33 invasive or microinvasive cancers and 10 dysplasias (CIN) were detected. The prevalence of invasive cervical cancer in that population was 15.6/1000. Risk factors were shown to be age over 35 (especially over 50), parity over six (especially more than 10), very low income or subsistence economy, particularly in those from the rural areas, and prostitution. Less significant factors, possibly related to age, were sexual activity of more than 20 years and first coitus before the age of 15; and more than five sexual partners. Most (66%) of women with invasive cancer were at stage 3 or 4. PMID- 1511119 TI - Measuring proliferation in routine fine needle aspirates. Immunocytochemical detection of bromodeoxyuridine incorporation and Ki-67 expression in breast aspirates. AB - Two simple quantitative means of measuring tumour proliferation which can be applied to cytological material are described. One method involves immunocytochemical staining of cytological smears prepared from breast aspirates with the monoclonal antibody Ki-67. The other method involves incubation of aspirated material with 5-Bromo-2-deoxyuridine (BrdU). Direct measurement of the S phase of the cell cycle is feasible in breast fine needle aspirates by Bromodeoxyuridine incorporation and subsequent immunocytochemical detection. The proliferation indices obtained correlate with those derived from Ki-67 staining. This technique is suitable for routine use in the assessment of tumour proliferation. PMID- 1511120 TI - Comparison of four immunochemical methods for the measurement of oestrogen receptor levels in breast cancer. AB - Four methods of assessing oestrogen receptor (ER) status were compared in 33 patients with operable primary breast cancer. The methods used to assess the ER status were immunocytochemical assay (ER-ICA) of frozen sections, fine needle aspirates and imprint material and enzyme immunoassay (ER-EIA) of tumour tissue. A mean overall ER positivity of 45% (15 out of 33), 41% (13 out of 32) and 21% (six out of 29) was obtained by immunocytochemical (ER-ICA) staining of frozen sections, fine needle aspirates and tumour imprints, respectively, and a mean overall ER positivity of 42% (14 out of 33) was obtained by ER-EIA. The concordance of ER positivity in pairs of data obtained from different method combinations was found to range between 72 and 91%. However, statistically there was no significant difference between the four methods on the basis of the data obtained. Good comparability has been shown between the three tissue analyses and therefore the method of choice is technically not immediately apparent. PMID- 1511121 TI - Immunocytochemical staining of ovarian tumours with Ov632. AB - Ov632 monoclonal antibody, said to be highly specific for ovarian tumour tissue, was used to stain ovarian tumour cells in a variety of specimens to determine its sensitivity. Thirteen of the 41 samples investigated were negative suggesting a low sensitivity for Ov632. PMID- 1511122 TI - Post-irradiation cytology of cervical cancer patients. AB - The accuracy of cervicovaginal cytology following radiotherapy for cervical cancer is compromised by the anatomical and tissue changes resulting from irradiation. Collection of representative samples may be more difficult, and benign radiation changes, post-irradiation dysplasia, and the frequent occurrence of repair cells and active stromal cells in post-irradiation smears may cause diagnostic problems. Nevertheless, cytology is a valuable tool for the detection of locally recurrent cervical cancer. It is simple and economical to perform at the time of clinical follow-up examination, and may detect occult tumour recurrence. Awareness of the cellular changes resulting from irradiation, and the varied composition of post-irradiation smears may lead to more accurate interpretation of the cytological findings. PMID- 1511123 TI - 'Ciliated' tumour cells in ascitic fluid from two cases of cystadenocarcinoma of the ovary. AB - We report two cases of primary carcinoma of the ovary in which 'ciliated' adenocarcinoma cells were found in the ascitic fluid. Transmission electron microscopy revealed that these were not true cilia but rather a prolific growth of abnormal microvilli. The cytological findings were compared with the histological appearances of the primary tumour. No ciliated cells were seen in the primary tumour, suggesting that the formation of the microvilli represented an independent proliferation of the cells in the fluid. Special staining reactions for mucin, alkaline phosphatase and epithelial membrane antigen were identical in the primary tumour and the cells in the ascitic fluid. PMID- 1511124 TI - Metastatic breast cancer presenting as an ovarian cyst: diagnosis by fine needle aspiration cytology. AB - A fifty-year-old woman with a history of breast cancer presented with a clinically benign ovarian cyst. Laparoscopic aspiration of cyst fluid was performed and the cytology was suspicious of epithelial neoplasia. At subsequent hysterectomy and bilateral salpingo-oophorectomy, the specimen showed extensive metastatic breast carcinoma. Although the cytological examination of fluid from ovarian cysts is often unrewarding, this case shows that metastatic carcinoma may occasionally be diagnosed in this fashion. PMID- 1511125 TI - A 16 kb small single-copy region separates the plastid DNA inverted repeat of the unicellular red alga Cyanidium caldarium: physical mapping of the IR-flanking regions and nucleotide sequences of the psbD-psbC, rps16, 5S rRNA and rpl21 genes. AB - The four inverted repeat (IR) flanking regions of the Cyanidium caldarium plastid DNA were cloned. Southern blotting, transcript and sequence analyses of the border regions revealed the psbD-psbC operon and the rps16 gene within the large single-copy region upstream of the 16S rDNA gene and the rpl21 gene downstream of the 5S rDNA within the 16 kb small single-copy region. The size of the IR is ca. 5 kb. The nucleotide sequences of the psbD-psbC, rps16, rpl21 and 5S rRNA genes with the corresponding alignments and physical maps of the regions are presented. Northern analysis revealed a less complex psbD-psbC transcription pattern than has been found in higher plants. Comparisons to other red algal data point to structural diversity within red algal plastid DNA. PMID- 1511126 TI - Lectin genes from the legume Medicago truncatula. AB - We report the cloning and characterization of two lectin genes from Medicago truncatula, designated Mtlec1 and Mtlec2. The two genes show a high degree of homology and apparently belong to a small multigene family. Mtlec1 appears to encode a functional lectin with 277 amino acids, whereas Mtlec2 is probably non functional, since a frameshift mutation (insertion of two nucleotides) leads to premature translation termination after only 98 amino acids. The deduced amino acid sequence of the polypeptide MtLEC1 suggests that this lectin is a metalloprotein with Glc/Man specificity. PMID- 1511127 TI - Factors affecting the rate of T-DNA transfer from Agrobacterium tumefaciens to Nicotiana glauca plant cells. AB - Different factors involved in the early steps of the T-DNA transfer process were studied by using a beta-glucuronidase gene (gusA) as a reporter in Nicotiana glauca leaf disc transformation experiments. The levels of transient expression of the gusA gene in leaf discs infected with several strains or vir mutants correlated well with their virulence phenotype, except for virC mutants. The rate of T-DNA transfer was shown to be stimulated in the case of non-oncogenic strains by the co-transfer of small amounts of oncogenic genes. It was found that the location of the T-DNA in the Agrobacterium genome affected the T-DNA transfer rate especially in virC mutants. The virC mutants transferred the gusA-containing T-DNA located on a binary vector more efficiently than the oncogenic T-DNA of the Ti plasmid. Although wild-type strains induced high levels of gusA expression early after infection, the gusA expression appeared to be lost late after infection in the infected leaf discs. In contrast, in leaf discs infected by virC mutants the level of gusA expression increased steadily in time. A model explaining these results is presented. PMID- 1511128 TI - Nucleotide sequence of the 5S rRNA gene from Glycine soja. PMID- 1511129 TI - Molecular analysis of a cruciferin storage protein gene family of Brassica napus. AB - We have isolated a five-member gene subfamily which encodes cruciferin, a legumin like 12S storage protein of Brassica napus L., and have analyzed the structure and expression of the family members in developing embryos. Sequence analysis has shown that the coding regions of all five genes are highly similar, with the two most divergent members of the family retaining 89% sequence identity. The analysis of this cruciferin gene family's expression indicates that the developmental pattern of expression of each gene is similar, and the steady-state mRNA levels of each gene are approximately equivalent to each other at all developmental stages. PMID- 1511130 TI - Information contents and dinucleotide compositions of plant intron sequences vary with evolutionary origin. AB - The DNA sequence composition of 526 dicot and 345 monocot intron sequences have been characterized using computational methods. Splice site information content and bulk intron and exon dinucleotide composition were determined. Positions 4 and 5 of 5' splice sites contain different statistically significant levels of information in the two groups. Basal levels of information in introns are higher in dicots than in monocots. Two dinucleotide groups, WW (AA, AU, UA, UU) and SS (CC, CG, GC, GG) have significantly different frequencies in exons and introns of the two plant groups. These results suggest that the mechanisms of splice-site recognition and binding may differ between dicot and monocot plants. PMID- 1511131 TI - Isolation and characterization of a cDNA clone encoding a novel jasmonate-induced protein of barley (Hordeum vulgare L.). PMID- 1511132 TI - Nucleotide sequence of a 5.8S rDNA gene and of the internal transcribed spacers from Populus deltoides. PMID- 1511133 TI - Direct sequencing of tobacco chloroplast genome by the polymerase chain reaction. AB - We have developed a polymerase chain reaction (PCR) method for sequencing of tobacco chloroplast genome. In a mixture containing chloroplast DNA, 5'-end labeled oligonucleotide primer, Taq DNA polymerase and reaction buffer, we were able to sequence a segment of chloroplast 16S rRNA gene. The results showed that the 750 bp of DNA sequenced were identical to the sequence reported, indicating that direct sequencing method that we have developed is useful for the sequencing of chloroplast genome. To analyze the chloroplast genome more rapidly in those in vitro grown plantlets, we also developed a simple method which is applicable for the amplifications and sequencing of chloroplast 16S rRNA fragment from either 0.15 g of tobacco leaf or stem tissue. The readable sequences obtained from the presented methods were consistent with the published sequence. PMID- 1511134 TI - Sequence of an oleosin cDNA from Brassica napus. AB - Antibodies raised against purified rapeseed 19 kDa oleosin protein were used to screen an embryo-derived lambda gt11 expression library from Brassica napus. A near full-length cDNA clone, BnV, was isolated. The 781 bp cDNA contained an open reading frame of 549 bp followed by an untranslated region of 222 bp and a poly(A) region of 10 bp. Comparisons between this cDNA and a different oleosin cDNA previously isolated from the same library showed high degrees of sequence similarity in the central domain region and in the 3' untranslated region. Sequence similarities between the derived protein sequence of this cDNA and all other known oleosin protein sequences are discussed. PMID- 1511135 TI - Aleurone nuclear proteins bind to similar elements in the promoter regions of two gibberellin-regulated alpha-amylase genes. AB - Binding of nuclear proteins from wild oat aleurone protoplasts to the promoter regions of two gibberellin-regulated wheat alpha-amylase genes (alpha-Amy1/18 and alpha-Amy2/54) has been studied by gel retardation and DNase 1 footprinting. Gel retardation studies using 300-430 bp fragments of the promoters showed similar binding characteristics with nuclear extracts from both gibberellin A1-treated and untreated protoplasts. DNase 1 footprints localised binding of nuclear proteins from gibberellin A1-treated aleurone protoplasts to regions in both promoters. Similar sequence elements in the promoter regions of both genes were protected from digestion although the location and number of footprints in each promoter region were different. Each footprint contained either a sequence similar to the cAMP and/or phorbol ester response elements, or a hyphenated palindrome sequence. The presence of cAMP and/or phorbol ester response element like sequences in the footprints suggests that transcription factors of the bZIP type may be involved in the expression of alpha-amylase genes in aleurone cells. Footprints containing hyphenated palindrome sequences, found in the promoter regions of both genes, suggest the possible involvement of other classes of transcription factor. The conserved alpha-amylase promoter sequence TAA-CAGA was also shown to bind nuclear protein in the alpha-Amy2/54 promoter. These observations are discussed in relation to alpha-amylase gene expression in aleurone and to functional data concerning these genes. PMID- 1511136 TI - Localisation of cis elements in the promoter of a wheat alpha-Amy2 gene. AB - A functional analysis of the promoter from the wheat alpha-amylase gene alpha Amy2/54 is described. Mutant alpha-Amy2/54 promoters containing replacements or deletions were constructed and their ability to direct expression of the reporter gene beta-glucuronidase (GUS) in gibberellin-responsive oat aleurone protoplasts analysed. Chimaeric promoters using regions of the cauliflower mosaic virus (CaMV) 35S and alpha-Amy2/54 promoters were also analysed. The results suggest that at least three regions within the alpha-Amy2/54 promoter contain cis elements that are necessary for high-level gibberellin-regulated transcription. Fusion of 1.8 kb of promoter sequence upstream from -117 bp to a minimal (-55 CaMV 35S) promoter gave rise to hormone-independent expression implying that the region 3' to -117 bp contains an element which represses transcription in the absence of gibberellin or presence of abscisic acid. PMID- 1511137 TI - Sequence and transcription analysis of mitochondrial plasmids isolated from cytoplasmic male-sterile lines of Vicia faba. AB - Three mitochondrial plasmids (1704, 1695 and 1478 bp) were isolated from sterile cytoplasms of Vicia faba L. and cloned into a bacterial plasmid vector. Their nucleotide sequence was found to be 99 to 100% homologous to their counterparts isolated from a fertile cytoplasm (J.A. Wahleithner and D.R. Wolstenholme, Curr Genet 12 (1987) 55-76). Several overlapping transcripts were localized in the region which is unique to each of the three plasmids. S1 nuclease mapping indicated for all of them several 3' termini but a unique 5' boundary which was located downstream of the consensus sequence CNTAAGTGANNNNNGAA also found at the transcript 5' boundary of other plant mitochondrial plasmids. Southern blot hybridization with nuclear DNA indicated the presence of nuclear sequences homologous to each plasmid. PMID- 1511138 TI - Genetic transformation of Norway spruce (Picea abies (L.) Karst) using somatic embryo explants by microprojectile bombardment. AB - Stable transformation of Norway spruce tissue has been obtained following bombardment of mature somatic embryos with pRT99gus, a plasmid that contains neo coding for NPTII, and gusA, coding for beta-glucuronidase, both fused to the CaMV 35S promoter. At least 8 lines have been stably transformed (over 15 months in culture) following bombardment and selection on kanamycin. Polymerase chain reaction analyses showed a high frequency of cotransformation of the gusA and neo genes. The frequency of coexpression of the selected and unselected markers was 100%. DNA/DNA hybridization of one transformed line provided conclusive evidence of stable integration and showed copy numbers of over 10 plasmid sequences per genome. None of the transformed lines has remained embryogenic. PMID- 1511139 TI - The legumin boxes and the 3' part of a soybean beta-conglycinin promoter are involved in seed gene expression in transgenic tobacco plants. AB - beta-conglycinin is one of the major seed storage proteins in soybean. It is composed of three subunits, namely alpha, alpha' and beta. The expression of beta conglycinin is highly regulated, being restricted to the embryo during the mid maturation phase of embryogeny. Two series of constructs were made with the alpha' subunit promoter and the GUS reporter gene to investigate the cis-acting elements involved in the regulated expression of this promoter. The activity of each construct was tested in transgenic tobacco plants. In the first series of constructs, we checked if the 'legumin box', a sequence found in most legume seed storage protein genes as well as in other seed-specific genes, is involved in the regulated expression of the alpha' subunit of the beta-conglycinin gene in tobacco. To this end, both copies of the alpha' subunit promoter legumin boxes were mutagenized in vitro. The transcriptional activity of the single mutants and the double mutant were compared with that of the wild-type promoter. Our results show that the legumin boxes act together to increase transcription of the beta conglycinin alpha' subunit gene by about a factor of ten. This is the first demonstration of a function for the legumin box in transcriptional regulation. In the second series of experiments, we wished to determine if the 3' part of the promoter (the CCAAT and TATAA region) contains important regulatory elements. We found that this small fragment (-82 to +13 bp) can confer by itself a low level of seed-specific gene expression. Chimaeric promoters constructed from parts of the alpha' subunit promoter and of the constitutive CaMV 35S promoter were also analysed. These constructs also revealed the importance of the CCAAT and TATAA region of the alpha' subunit promoter in seed-specific gene expression. PMID- 1511140 TI - Constitutive expression of the beta-phaseolin gene in different tissues of transgenic alfalfa does not ensure phaseolin accumulation in non-seed tissue. AB - Phaseolin is a glycoprotein that constitutes the major storage protein in bean seeds. The phaseolin gene promoters function in a seed-specific manner. In an attempt to understand if events following transcription of the gene also contribute to the seed-specific accumulation of the phaseolin protein, we studied the effect of substituting the constitutive CaMV-35S promoter for the beta phaseolin gene promoter on expression of the phaseolin gene in different plant organs. A chimeric gene consisting of the 35S promoter, the coding sequence of the beta-phaseolin gene (all five introns and six exons) and the 3'-flanking region of the beta-phaseolin gene, was introduced into alfalfa via Agrobacterium tumefaciens. While all organs examined shared high levels of phaseolin transcripts, the only organ that showed significant accumulation of the phaseolin protein were the mature seeds. Co-migration of the major immunoreactive polypeptides from the non-seed organs with the authentic beta-phaseolin polypeptides on SDS-PAGE indicates that the protein in non-seed organs undergoes correct post-translational processing and modification, but are more unstable in a non-seed environment. PMID- 1511141 TI - Characterization and expression of U1snRNA genes from potato. AB - U1 small nuclear RNAs (U1snRNAs) occur in the nucleus of plants and animals where, complexed with several proteins in the form of U1 small nuclear ribonucleoprotein particles (U1snRNPs), they play an important role in precursor messenger RNA (pre-mRNA) splicing. Ten potato U1snRNA genes have been isolated on two genomic clones illustrating the clustering of this multigene family on the potato genome. Based on both the sequence of their coding regions and upstream regulatory elements, seven of the genes are potentially functional. The other three genes were pseudogenes with defective promoter or coding region sequences. Analysis of expression of individual cloned U1snRNA genes in transfected tobacco protoplasts was impossible due to the similarity of U1snRNA sequences in tobacco. However, by marking the coding regions with oligonucleotides or constructing chimaeric genes consisting of a potato U1snRNA promoter region and maize U5snRNA coding region, three of the U1 promoter regions were shown to be transcriptionally active. PMID- 1511142 TI - Characterization of the U3 and U6 snRNA genes from wheat: U3 snRNA genes in monocot plants are transcribed by RNA polymerase III. AB - We have demonstrated recently that the genes encoding the U3 small nuclear RNA (snRNA) in dicot plants are transcribed by RNA polymerase III (pol III), and not RNA polymerase II (pol II) as in all other organisms studied to date. The U3 gene was the first example of a gene transcribed by different polymerases in different organisms. Based on phylogenetic arguments we proposed that a polymerase specificity change of the U3 snRNA gene promoter occurred during plant evolution. To map such an event we are examining the U3 gene polymerase specificity in other plant species. We report here the characterization of a U3 gene from wheat, a monocot plant. This gene contains the conserved promoter elements, USE and TATA, in a pol III-specific spacing seen also in a wheat U6 snRNA gene characterized in this report. Both the U3 and the U6 genes possess typical pol III termination signals but lack the cis element, responsible for 3'-end formation, found in all plant pol II-specific snRNA genes. In addition, expression of the U3 gene in transfected maize protoplasts is less sensitive to alpha-amanitin than a pol II transcribed U2 gene. Based on these data we conclude that the wheat U3 gene is transcribed by pol III. This observation suggests that the postulated RNA polymerase specificity switch of the U3 gene took place prior to the divergence of angiosperm plants into monocots and dicots. PMID- 1511144 TI - A model for quality assessment in cervical cytology used as a screening test. AB - Although many reliability studies on cervical cytology have been carried out, measurements of sensitivity and specificity have rarely been made since biopsies are not often performed on patients with a negative smear result. This screening assessment was performed over 3 years, using a database of 230,167 smears from 177,051 women. It would seem that cervical cytology has a high specificity (over 99%) but a relatively low sensitivity (61%). Values for sensitivity (exceeding 95%) and specificity (exceeding 99%) for invasive carcinoma should be regarded as reasonably accurate as all incident cases of symptomatic cervical carcinoma are recorded in the Burgundy register. The sensitivity (57%) for pre-invasive lesions is underestimated while their prevalence is overestimated: the lack of organized screening leads to the loss of prevalent cases. The predictive value of a positive smear is 76% for moderate-severe dysplasia, 85% for in situ carcinoma and over 95% for invasive carcinoma. PMID- 1511145 TI - The Flemish Centre for the Study of Perinatal Epidemiology and its registry. AB - The Flemish Centre for the Study of Perinatal Epidemiology was formally established in 1986. Its objectives are the promotion of perinatal epidemiology and the study of maternal and perinatal mortality and morbidity. One of the means to accomplish these objectives was the creation of a databank of perinatal medicine. The registry at present covers almost 80% of all deliveries in Flanders. The registry indicates a maternal death rate of 5.8/100,000 living births whereas the Belgian official national statistics indicate a maternal death rate of 2.8/100,000. This means that either the matter is under reported at the national level or there is a real problem in the Flemish part of the country. The perinatal death rate varies among the participating services form 3.9 to 22.4%. PMID- 1511143 TI - AT-rich promoter elements of soybean heat shock gene Gmhsp17.5E bind two distinct sets of nuclear proteins in vitro. AB - A 33 bp double-stranded oligonucleotide homologous to two AT-rich sequences located upstream (-907 to -889 and -843 to -826) to the start of transcription of heat shock gene Gmhsp17.5E of soybean stimulated transcription when placed 5' to a truncated (-140) maize Adh1 promoter. The chimeric promoter was assayed in vivo utilizing anaerobically stressed sunflower tumors transformed by a pTi-based vector of Agrobacterium tumefaciens. Nuclear proteins extracted from soybean plumules were shown to bind double-stranded oligonucleotides homologous to AT rich sequences in the 5' flanking regions of soybean beta-conglycinin, lectin, leghemoglobin and heat shock genes. These proteins were also shown to bind AT rich probes homologous to homeobox protein binding sites from the Antennapedia and engrailed/fushi tarazu genes of Drosophila. Binding activity specific for AT rich sequences showed a wide distribution among various plant organs and species. Preliminary characterization indicated that two sets of nuclear proteins from soybean bind AT-rich DNA sequences: a diverse high-molecular-weight (ca. 46-69 kDa) group, and a low-molecular-weight (23 and 32 kDa) group of proteins. The latter meets the operational criteria for high-mobility group proteins (HMGs). PMID- 1511146 TI - What makes outpatient attendance worthwhile for patients? AB - All patients attending 10 general medical and general surgical outpatient clinics at a provincial teaching hospital were surveyed during a 1-week period. Questionnaires administered and completed by the patients at the time of the visit were used to establish the factors most closely associated with patients feeling that their consultations had been "very worthwhile". These were: consultations lasting more than 10 min, having received advice from a specialist and having been reassured. The study may provide a basis for a process of medical audit in outpatient departments and, thus, more appropriate services. PMID- 1511147 TI - Need for and influence of feedback from the Finnish birth register to data providers. AB - Data for the Finnish medical birth register (established 1987) are collected by local hospital personnel as a part of their routine work. The purpose of this study was to study the need of personnel for feedback and the impact of feedback on later data quality. Furthermore, we studied whether such feedback tends to modify extreme cesarean section rates. Data on attitudes towards the birth register and on the need for feedback of data providers were collected through interviews and observations. In March 1988, an information package describing births, birth procedures and infant outcomes in each hospital compared with other hospitals was sent to a random stratified sample of 26 hospitals out of a total of 53. Opinions of the package were obtained by questionnaire from 104 physicians and nurses (82% response rate). Most hospital personnel, especially physicians, had negative attitudes towards the birth register. Comparison of the hospitals which had received feedback with other hospitals in terms of quality of data furnished in 1987 and 1988 suggested that feedback may improve the technical quality of data. There was no evidence, however, that feedback caused hospitals to change their practices in regard to cesarean sections. PMID- 1511148 TI - Quality assurance in urine analysis. AB - An Australian quality control (QC) system was tested on its ability to detect analytical errors in calcium, creatinine, oxalate, phosphate and uric acid determinations in urine. This QC system revealed that our methods for calcium and urate worked well. The oxalate values were systematically higher than the assigned values and the random error was too high. Phosphate and creatinine had a marked positive deviation in the higher range of concentration but agreed better in the medium and lower ranges. The findings emphasize the need for external QC systems in urine analysis. We also discuss specific problems with urine QC compared with conventional QC for serum, the theoretical basis of creatinine corrected urinary analytes and criteria for rejection and warning limits. We conclude that QC of urine analysis is as important as that of serum and that such programs should be used in concordance with serum QC programs. PMID- 1511149 TI - Group judgments of appropriateness: the effect of panel composition. AB - The current interest in the development of practice guidelines raises an important question about the effect of expert panel composition on the outcome of the guideline development process. We compared the ratings of appropriateness of indications for carotid endarterectomy produced by two panels: an all-surgical panel and a "balanced" panel composed of four surgeons, two neurologists, and one specialist each from family practice, internal medicine, and radiology. We then compared the effect of the two sets of ratings when used to evaluate 1302 patients who had undergone carotid endarterectomy. The all-surgical panel found more indications "appropriate" (24 versus 14%) and fewer indications "inappropriate" (61 versus 70%) than the balanced panel (p less than 0.01). The all-surgical panel also more often reached agreement. When ratings were applied to patients, 70% were appropriate by the all-surgical criteria versus 38% by the balanced panel, while 19% of the operations were inappropriate by all-surgical criteria, versus 31% by the balanced panel ratings. However, the percentage of procedures judged "inappropriate with agreement" was 15% for all-surgical and 16% for the balanced panel. We conclude that the all-surgical panel was more likely to favor operative treatment for carotid disease than the multispecialty panel, but that concensus judgments of inappropriateness by the two panels were very similar. PMID- 1511150 TI - Reactions of doctors to various forms of feedback designed to improve the sampling quality of cervical smears. AB - Three different forms of feedback designed to improve the sampling quality of cervical smears were tested in a randomized controlled trial among 179 physicians. The reactions of the doctors to the various interventions are reported as they appeared from their answers in a questionnaire. The influence of the interventions on the employed sampling technique is described on the basis of their answers to a telephone inquiry. The inclusion in laboratory protocols of an evaluation of the sampling quality of the submitted smears was largely appreciated, as was specific advice offered on indication. Monthly overviews comparing the performance of the individual doctor to that of his peers were esteemed by three out of four. Further information, help or training was requested more frequently than average by physicians obtaining inadequately sampled smears relatively often. The number of doctors using the combined spatula and Cytobrush method as sampling technique doubled during the study period. PMID- 1511151 TI - Medical audit and quality of care--a new English initiative. AB - In 1989 the Government in the UK announced a fundamental review of the financing of the National Health Service (NHS). Before the review, health authorities were responsible for both establishing need and providing services. Health Authorities are now allocated resources with which they commission services from managerially independent provider units. In the discussion that preceded the review concern was expressed about standards of clinical care given by doctors. It was recognised that these were professional issues which could not be directly addressed through the commissioning process, therefore within its NHS review proposals, the Government made clear its expectation that all doctors working in the NHS should participate in medical audit. This was defined as a systematic peer review of their work, including procedures used for diagnosis and treatment, the use of resources and the resulting outcome for patients. Managers should be provided with regular general reports of audit activity. These proposals for medical audit have been well received by the medical profession, who are now working closely with the Government to put them into practice. PMID- 1511152 TI - The quality improvement system in the hospitals of Padua (Italy). AB - A quality improvement system has been established in 1989 in the hospital network of Padua and its organization is described. Three selected experiences are reported. (1) Appropriateness of the use of human albumin. After the assessment of the clinical policy, new guidelines were experimentally introduced and an evaluation after 3 months has shown a decrease of the total number of prescriptions (25%) and of inappropriate indications (9% vs 40.1%). (2) Urinary Tract Infections (UTI) and indwelling catheterization. The study showed 49% of conditions related to UTI and some corrigible inadequacies in the process of care: 37.2% of indications were probably not justified; 40% of patients who did not undergo urineculture had indications and 13% who underwent urineculture had no indications to the test. Guidelines for appropriate indications and a continuing education programme have been introduced. (3) Falls by hospitalized patients. The patient fall rate was 0.3/1000. As the reporting system showed inaccuracies (for example, the severity of injury was not collected in 34% of cases), a new notification form was introduced in 1991. PMID- 1511153 TI - The retinoblastoma protein and the cell cycle. AB - Although mutations of the retinoblastoma gene (RB1) contribute to malignant progression in many types of tumor, the role of RB1 mutation in cancer initiation is highly restricted to the rare embryonic tumor, retinoblastoma. However, RB1 is expressed and its product, p110RB1, is regulated through the cell cycle in many tissues. This apparent paradox may be clarified by the emerging evidence that p110RB1 functions as a regulator of transcription of cell cycle genes. Tissue specific effects may be determined by the cellular proteins that interact with p110RB1, or by cell type-specific expression of target genes regulated by p110RB1. PMID- 1511154 TI - Neurofibromatosis: from gene to phenotype. AB - Neurofibromatosis type 1 (NF1) is a common autosomal dominant disease which predominantly affects tissues derived from neural ectoderm. The gene has recently been cloned, and the biochemistry and cell biology of normal and mutant forms is gradually being elucidated. Despite the success of cloning the gene, there is a long way to go before the different features of the disease phenotype can be explained. Some of the questions which arise in the attempt to link the mutation to the phenotype are considered, with possible ways to approach them. PMID- 1511155 TI - The role of tumour suppressor genes in familial cancer. AB - Many forms of cancer have a higher incidence in relatives of patients than in the general population, and some show Mendelian inheritance. Although individuals genetically predisposed to cancer represent a minority of all cancer patients, the genetic basis for their disease has profound significance. These familial cases provide strong evidence that germline alterations can contribute to cancer. They also provide an ideal opportunity to identify and isolate the genes mutated in common cancers. Products of the tumour suppressor genes have been implicated in several hereditary forms of cancer. The distinct functions of these proteins and their roles in familial cancer will be discussed. PMID- 1511156 TI - Familial breast cancer. AB - Familial clustering of breast cancer has been recognised for over a century but until recently a genetic basis has been suspected rather than proven. Epidemiological studies have tended to support the view that an autosomal dominant gene, with high but incomplete penetrance, accounts for most breast cancer families. However, it is likely that several different predisposing genes are present within most populations. Difficulties arise in a conventional 'linkage mapping' approach to identifying these genes, first, because it is not clear that genetically homogeneous groups of families can be recognised on the basis, for example, of mean age of onset or pattern of other cancers within the kindred and, second, because breast cancer is so common (affecting almost one in twelve women) that large affected kindreds are likely to include an admixture of sporadic (non-genetic) cases. Cytogenetic and 'Loss of Heterozygosity' (LOH) studies in sporadic breast cancers have pointed to several candidate loci for breast cancer genes but there is no clear consensus from these two approaches that might direct attention to any prime target region. Recent reports of tight linkage between familial breast cancer (early onset) and breast/ovarian cancer (regardless of mean age of onset) and a locus on chromosome 17q21 defined by the anonymous probe CMM86, have not been confirmed in detail but have led to the identification of a locus some 15 Mb centromeric of CMM86 that gives a high positive lod at very low recombination fraction in fifteen Edinburgh breast and breast/ovarian cancer families. The disease in the majority of such families therefore appears to be attributable to a mutant gene at 17q12-21. A much smaller proportion of familial breast cancer is accounted for by mutations in the p53 gene (17p13). Not all such families fulfil the criteria for Li-Fraumeni syndrome and not all of the inherited mutations lie within exon 7 of p53. Counselling of members of breast cancer families becomes more exacting as these genetic lesions are identified. It is essential to extend the collection of data and tissue (blood or fixed pathology material) as widely as possible to confirm linkage to a specific locus within each individual kindred, to define the precise mutation and to establish the cancer phenotype and its penetrance. In the course of these studies a substantial population of women at high risk of breast (and other) cancer will be identified. Resources should be directed to this population so that optimum procedures for screening and prevention can be developed. PMID- 1511157 TI - Genome imprinting and cancer genetics. AB - Parent-of-origin-dependent modification of the genome (genome imprinting) is thought to be involved in the formation of several types of human cancer. Simple modifications of Knudson's two-hit model give rise to two types of predictions with respect to the genetic behavior of such diseases. In the first, rare alleles of modifier genes will give rise to the retention of the same parent's tumor suppressor alleles in sporadic cases. In the second, other variants of the modifier genes will result in failure to establish linkage between tumor suppressor genes and disease predisposition in familial cases. Both of these predictions are fulfilled by experiment. Additional modifications of existing models are predicted to result in more complex patterns of inheritance. The demonstration of such patterns in human pedigrees will require an extremely sophisticated level of genetic analysis. PMID- 1511158 TI - Genetic resolution of susceptibility to cancer--new perspectives. AB - Neoplastic development is under strong genetic control, which results in large differences in tumor susceptibility between individuals of the same species. These differences are caused by tumor susceptibility genes (TSGs). The characteristic features of TSGs are frequent polymorphism, influence on specific aspects of the tumorigenic process, and tissue specificity. In contrast to cellular oncogenes and tumor suppressor genes, which in most instances require somatic alterations to become engaged in the tumorigenic process, the allele specific effects of TSGs are encoded in the germ-line. Until recently, the TSGs have remained virtually unknown despite many efforts to map them. Their multiplicity and incomplete penetrance defied the available genetic methods. Therefore a novel genetic tool, the Recombinant Congenic Strain (RCS) has been developed in the mouse (P. Demant and A.A.M Hart, Immunogenetics 24:416-422), which allows dissection of multigenic control and mapping of the genes contributing to it. When applied to colon tumors, the RCS revealed separate genetic control for tumor numbers and tumor size, and allowed mapping of several TSGs. The presently available RC strains allow the genetic and functional dissection of virtually all major types of mouse tumors. This opens the possibility to map, within a relatively short period, the TSGs for various organs, to study the functional effects of individual TSGs and the possible interactions of this new class of genes with the known oncogenes and tumor suppressor genes. The extensive information about the chromosomal homologies between man and mouse will facilitate the search for their human counterparts once the TSGs in mouse are mapped. PMID- 1511159 TI - Stem cell regulation, tissue ontogeny, and oncogenic events. AB - The number of necessary oncogenic events is a function of tissue ontogeny. A minimum of two events appears to suffice for certain embryonal tumors, leukemias, and lymphomas for which the target tissues normally show stem cell proliferation. Other tumors, including those featured in the Li-Fraumeni syndrome, arise in target tissues whose stem cells are conditionally stimulated to proliferate, as in response to hormones, and involve more events. The most complex cancers include most carcinomas, which arise in renewal tissues whose stem cells do not normally proliferate. The number of necessary oncogenic events appears to increase with the number of controls on proliferation. PMID- 1511160 TI - The effect of phlebotomy on serum erythropoietin levels in normal healthy subjects. AB - We evaluated endogenous serum erythropoietin (Epo) levels in 14 normal subjects (eight males and six females) after a single 400-ml phlebotomy. The subjects were followed up for 56 days. The hemoglobin (Hb) values of both males and females decreased to a nadir on days 3 to 7 post-phlebotomy. Hb values gradually increased, but did not completely recover to pre-phlebotomy levels by day 56. Serum Epo levels increased after 6 h post-phlebotomy, to 20.1 +/- 5.4 (mU/ml) in males and 20.7 +/- 7.0 in females, from the pre-phlebotomy levels of 14.6 +/- 4.0 in males and 13.4 +/- 4.1 in females, respectively. Epo levels continued to increase to peak levels of 25.5 +/- 6.3 in males and 28.7 +/- 11.5 in females on days 7 to 14 and thereafter decreased until day 56. Thus, the Epo response to a 400-ml phlebotomy was relatively small in magnitude and was not sufficient to initiate a significant increase in erythropoiesis. This finding suggests that the administration of recombinant human erythropoietin (rHu-Epo) may be effective for the prompt correction of anemia induced by autologous blood donation and for increasing the volume of predonated autologous blood. PMID- 1511161 TI - Pernicious anemia in Turkey. AB - Pernicious anemia patients who were diagnosed during a 5-year period in Cukurova University Hospital, Adana, Turkey were reviewed. Of approximately 200 new patients per year accepted by the Hematology Unit 44 were diagnosed as having pernicious anemia. There were 30 males and 14 females. The mean age for men was 49.14 +/- 18.11 and that for women was 40.00 +/- 14.05. Both values and the mean age overall were lower than the reported mean age for Whites, Blacks and Latin Americans living in the United States. PMID- 1511162 TI - Ionizing radiation increases TNF/cachectin production by human peripheral blood mononuclear cells in vitro. AB - Human peripheral blood mononuclear cells (PBMC) and monocytes produce a large amount of tumor necrosis factor/cachectin (TNF) in vitro. Our data suggest that X irradiation can increase TNF production by these cells. After 900 cGy irradiation there were 7-fold (24 h incubation) and 2.3-fold (48 h incubation) increases of TNF production by stimulated PBMC. The irradiation also increased TNF production by both stimulated and unstimulated human monocytes. These findings suggest that TNF overproduction can play an important role in the pathogenesis of radiation disease. PMID- 1511163 TI - Identification and characterization of specific receptors for the LD78 cytokine. AB - LD78 is a small secreted protein that has a sequence similar to a number of other polypeptides, including murine macrophage inflammatory protein 1 alpha (MIP-1 alpha), interleukin 8 (IL-8), Act-2, monocyte chemoattractant protein 1 (MCP-1), and others. These polypeptides are members of a novel cytokine superfamily that is involved in the inflammatory response, wound healing, hematopoiesis, and tumorigenesis. Specific receptors for purified clonal LD78 protein were measured using four cell lines (HL-60, U937, Jurkat, and MJ). 125I-labeled recombinant LD78 bound most efficiently to U937 cells. We therefore characterized the receptors as being on the surface of U937 cells. Binding reached an equilibrium after incubation for 60 min at 4 degrees C. Scatchard analysis showed that there were two classes of binding sites on U937 cells, high affinity sites (Kd = 5.3 x 10(-9) M) and low affinity sites (Kd = 9.3 x 10(-8) M), with the average number of binding sites per cell being approximately 30,000 and approximately 90,000, respectively. These receptors for LD78 were distinct from the receptors for gamma IFN and for IL-8. SDS-PAGE analysis of chemically crosslinked 125I-labeled LD78 receptor complexes identified a single band of 52 kDa. The ability to detect specific LD78 receptors should prove valuable in efforts to molecularly clone these receptors and to dissect the biological actions of LD78. PMID- 1511164 TI - Serial changes of the serum macrophage colony-stimulating factor level after cytoreductive chemotherapy. AB - To investigate the physiologic role of macrophage colony-stimulating factor (M CSF) in hematological recovery from bone marrow hypoplasia, we used an enzyme linked immunosorbent assay to measure serial changes of the serum M-CSF level during 25 intensification chemotherapy courses given to seven patients with acute non-lymphocytic leukemia who were in complete remission. Three M-CSF peaks were observed during therapy: the first peak was during or just after chemotherapy, the second peak was around the leukocyte nadir, and the third peak coincided with a rapid increase in the monocyte count. We could find no significant correlation between the height of the second peak and the time from the initiation of therapy to hematological recovery. On the other hand, there was a significant positive correlation between the height of the second peak and the interval from the last day of chemotherapy to the peak (r = 0.62, p = 0.001), and there was a significant negative correlation between the peak height and the time from the peak until hematological recovery (defined as a neutrophil count of over 500/microliters (r = -0.63, p = 0.001) and a leukocyte count of over 1,000/microliters (r = 0.55, p = 0.008)). However, we found only a weak correlation between the peak height and monocyte recovery. These data suggest that increased M-CSF levels lead to the stimulation of granulocyte progenitors, and that we can predict the time of neutrophil recovery by monitoring the serum M CSF level and finding its peak. PMID- 1511165 TI - Treatment of chronic neutropenia of childhood responsive to cyclosporin A in vitro and in vivo. AB - The clinical course of a 17-year-old patient who suffered from chronic neutropenia without cyclic variation since the age of 2 is presented. The bone marrow showed absent granulopoiesis and yielded very few colony-forming units (CFU-GM) in vitro with maturation up to segmented neutrophils. Incubation with cyclosporin A (CyA) increased CFU-GM markedly. Such an increase was not found after incubation of normal bone marrow with CyA in vitro. The patient also responded to CyA in vivo and maintained adequate granulocyte counts for 7 months when she became neutropenic again. She subsequently responded to high doses of prednisolone. The clinical course and bone marrow studies suggest that the defective granulopoiesis is due to an immunologically mediated mechanism sensitive to CyA and prednisolone. Other findings in this patient, such as impaired natural killer (NK) cell activity and random and chemotactic leukocyte motility, could further point to an imbalance in the regulation of hematopoiesis. Neutropenia, NK cell defect and impaired chemotaxis may be pathogenetically connected. PMID- 1511166 TI - Bone marrow eosinophilia as a prognostic indicator in acute myelogenous leukemia with 8;21 translocation. AB - The pretreatment characteristics of nine acute myelogenous leukemia (AML) patients with 8;21 translocation were evaluated to assess their value as prognostic indicators. All patients had AML-M2 according to French-American British classification. The percentage of eosinophils in the bone marrow (EO/BM) correlated negatively with the percentage of blast cells in the peripheral blood (BL/PB) (p less than 0.05) and positively with complete remission duration (p less than 0.01). Three of the six patients with EO/BM under 5% showed aggressive clinical courses complicated with extra marrow lesions, while the patient with the highest EO/BM was the only one who survived for 5 years. These findings suggest that bone marrow eosinophilia could be useful as a prognostic indicator in AML patients with t(8;21). PMID- 1511167 TI - Possible mechanisms for the elevation of serum beta 2-microglobulin levels in adult T-cell leukemia. AB - In our previous study, we found that serum beta 2-microglobulin (beta 2M) levels were elevated in the active, but not in the inactive, phase of adult T-cell leukemia (ATL), suggesting a correlation between the beta 2M level and the clinical severity of this disease. In this study we examined the mechanisms underlying the elevation of serum beta 2M levels in ATL. First, the production of beta 2M by ATL cells was investigated in vitro. High levels of beta 2M were detected in the conditioned culture medium (CM) of ATL cells from seven out of nine patients. Second, we assessed the effects of the CM on the release of beta 2M by three human cell lines unrelated to ATL (NCTC 2544, Chang liver, and L 132; originating from the skin, the liver, and the fetal lung, respectively). Most of the CM definitely promoted beta 2M production by these cell lines. beta 2M production by the cell lines was markedly promoted by exogenous interferon-gamma (IFN-gamma), a well-known potent inducer of class I HLA antigen expression. We then investigated whether an antibody directed against IFN-gamma could attenuate the activity of three ATL CM. The anti-IFN-gamma antibody reduced the stimulatory activity of the CM to 28-65% of the original level, but did not affect basal beta 2M production by these cell lines. These data suggest that there are at least two mechanisms causing the elevation of serum beta 2M levels in ATL; direct production by tumor cells, and production by non-malignant cells that is mediated via humoral factors secreted by the ATL cells.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1511168 TI - The effect of recombinant human erythropoietin on hemostatic status in chronic uremic patients. AB - The hemostatic effects of recombinant human erythropoietin (rHuEP) were investigated in 20 patients with end-stage renal disease (thirteen on hemodialysis, seven without dialysis) receiving this hormone. We studied their hemograms and coagulation profiles before and at 1 month after initiation of rHuEP therapy. One month after rHuEP administration, improvement in anemia (16/20, 80%) and shortening of bleeding time (17/19, 89.5%) were observed. Shortening or correction of bleeding time was achieved in three patients without any increase of the hemoglobin level. This means that factors other than the increased hematocrit level might contribute to shortening bleeding time in uremic patients receiving rHuEP treatment. The platelet count, prothrombin time, partial thromboplastin time, and fibrinogen level did not change over the course of rHuEP therapy. Thrombosis of vascular access was not observed, and heparin doses were not increased in this short-term period. A significant decrease was found in the plasminogen level, from 108.5% to 88.2% (p less than 0.05), in uremic patients on hemodialysis. The antithrombin III level also decreased, from 98.8% to 89.8% (p less than 0.05), and its level dropped to below normal ranges in six of thirteen patients (46%) on hemodialysis after treatment with rHuEP. No significant change was noted in the levels of antithrombin III, plasminogen, and alpha 2-antiplasmin in uremic patients not receiving dialysis. These results suggest that rHuEP administration induces increased extracorporeal dialyzer clotting and consumption coagulopathy, and that this extracorporeal consumption coagulopathy may play a role in the genesis of thrombotic complications. PMID- 1511169 TI - Mullerian inhibiting substance binding and uptake. AB - Mullerian inhibiting substance (MIS) is a 140,000 M(r) Sertoli cell derived glycoprotein with a critical regulatory role in the male fetus initiated presumably by ligand binding with receptor. To localize this binding species we performed time course incubations of cultured fetal rat lungs or control tissues with MIS, applied rabbit anti-MIS IgG, and fluorescein conjugated anti-rabbit IgG, and examined specimens with laser confocal microscopy. Punctate surface fluorescence followed by cytosolic and nuclear localization in lung consistent with specific adsorptive endocytosis was seen. Confocal imaging also detected MIS binding to the Mullerian duct in the urogenital ridge. Crosslinking of 125I-MIS with plasma membranes revealed a high molecular mass binder with signal displaceable by excess unlabeled ligand. These data support the hypothesis that a specific plasma membrane binding protein for MIS exists. PMID- 1511170 TI - Effect of systemic calcium deficiency on the expression of transforming growth factor-beta in chick embryonic calvaria. AB - The developmental process of intramembranous ossification involves bone formation directly from mesenchymal differentiation without a cartilage intermediate. We have previously observed that systemic calcium deficiency in the developing chick embryo, produced by long-term shell-less culture, results in the appearance of chondrocyte-like cells in the calvarium, a parietal bone which normally develops via intramembranous ossification. This investigation aims to analyze the mechanism underlying this calcium deficiency-related, aberrant appearance of cartilage phenotype in the chick embryonic calvarium. In view of the reported involvement of transforming growth factor beta (TGF-beta) in osteogenesis and chondrogenesis, we have examined and compared here the expression of TGF-beta in the chick embryonic calvaria of normal (in ovo development, NL), shell-less (SL), and calcium-supplemented SL (SL+Ca) embryos. TGF-beta expression was analyzed at the mRNA level by blot and in situ cDNA hybridization, and at the protein level by immunohistochemistry and immunoblotting. The results presented here indicate that: 1) TGF-beta is expressed in the chick embryonic calvarium by both periosteal cells and osteocytes, as revealed by in situ hybridization and immunohistochemistry; 2) TGF-beta expression is significantly increased in SL calvarium compared to NL calvarium, at both protein and mRNA levels; 3) the number of TGF-beta expressing cells increases in the SL calvarium, particularly along the central, subcambial core region of the bone; and 4) exogenous calcium repletion to the SL embryo affects the expression of TGF-beta such that the pattern approaches that in the NL embryo. Taken together, these results indicate that altered TGF-beta expression accompanies the aberrant appearance of cartilage phenotype caused by systemic calcium deficiency. We postulate that normal cellular differentiation along the osteogenic pathway during embryonic intramembranous ossification is crucially dependent on regulated TGF-beta expression. PMID- 1511171 TI - Leg bud mesoderm retains morphogenetic potential to express limb-like characteristics ("limbness") in collagen gel culture. AB - Recent in situ hybridization studies have correlated expression of potential regulatory genes with pattern formation in limb bud mesoderm (Tabin: Cell 66:199 217, 1991); however, the mechanism(s) controlling their expression in mesoderm and their relevance to the establishment of a limb morphogenetic pattern remain unknown. One likely candidate for regulating patterning events in limb mesoderm is the apical ectodermal ridge, as its removal in ovo results in a graded truncation of limb skeletal elements in the proximal-distal axis dependent upon the time of excision (Rowe and Fallon: J Embryol Exp Morph 68:1-7, 1982). In the present study, we investigate whether the hypothetical imprint of ridge ectoderm is retained in cultured mesoderm. Specifically, we sought to determine if a subpopulation of limb mesoderm that forms in collagen gel culture (Markwald et al: Anat Rec 226:91-107, 1990), retains any expression of "limbness" in the absence of limb ectoderm as characterized by the formation of a predictable number and distribution of limb-like chondrogenic elements in comparison to the temporal and spatial relationships of the in situ proximal, hindlimb skeletal structures. Accordingly, explants of undissociated mesoderm from stage 18-22 chicken leg buds were cultured without ectoderm on collagen gel lattices and the central subpopulation of mesoderm was examined morphologically. We show that this central subset of mesoderm will form chondrogenic cells which were not expressed uniformly throughout the subset, but rather distinct nodules or elements of cartilage were elaborated. Moreover, the number of elements expressed by the central subset increased with the age of the mesoderm at the time of explantation; spatially and temporally, the sequence of elements that formed always proceeded from the proximal, anterior margin of the subset to its distal, posterior border. The shapes of the initial elements (designated I and II) resembled the forms of in situ proximal skeletal structures (girdle and femur like), whereas more distal elements (III-V) were often fused and without structural similarity to in situ skeletal structures. When cultures were established from the posterior mesoderm of stage 19/20 or 21 mesoblasts, the frequency of element I formation was reduced approximately one-half, whereas formation of more distal elements was unaffected. Conversely, element formation from the central subset established from isolated anterior mesoderm was virtually identical to intact mesoblasts, indicating a capacity to regulate for the loss of mesoderm as occurs in situ (Hampe: Archs Anat Microsc Morph Exp 48:345-378, 1959).(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1511172 TI - Developmental expression of two antigens associated with mouse intestinal crypts. AB - Two monoclonal antibodies were prepared against the duodenal mucosa of four-day old mice (MIM-1/39 and MIM 1/130). The expression of the antigens was associated with the crypts of the small and large intestine in the fetus and adult. MIM-1/39 was present in epithelial cells of the intervillous areas in the small intestine at 17 and 18 days of gestation; afterwards its expression was detected only in crypt cells from birth to adulthood. Transition from the mouth of the crypts to intestinal villi was abrupt. Expression of MIM-1/39 was first detected at time of birth in the colon: In the adult, only crypt cells expressed the antigen and goblet cells were negative. Antigen MIM-1/130 was detected from 16 to 18 days of gestation in the small intestine, in the mesenchymal matrix lying under the intervillous epithelium. After birth, it was present in the pericryptal mesenchymal matrix. This antigen was also expressed at birth in the colon and remained in the pericryptal matrix in the adult. In vivo, multiple injections of an organic extract of rat amniotic fluid to mothers, starting at 14 days of gestation, induced a profound modulation in the pattern of expression of both antigens at 17 days of gestation: The pattern of expression was comparable to that observed at least 5 days after birth in untreated animals. The expression of both antigens before crypt appearance may reflect some molecular differentiation in preparation for the formation of crypts, while their association with differentiated crypts may indicate that they have a role in the maintenance of crypt functional and/or morphological integrity.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1511173 TI - Expression of alpha-cardiac and alpha-skeletal actin mRNAs in relation to innervation in regenerating and non-regenerating rat skeletal muscles. AB - The expression of alpha-cardiac and alpha-skeletal actin mRNA in regenerating muscle was examined. Changes in mRNA levels were analyzed in autografted extensor digitorum longus (EDL) muscles in rats using alpha-isoform specific synthetic oligonucleotides and beta-actin cDNA as probes. After autografting, the expression of alpha-cardiac actin mRNA was induced; concomitantly that of alpha skeletal actin mRNA was reduced. The pattern of alpha-actin mRNA expression appeared to be similar to that seen in embryonic skeletal muscle. In order to evaluate the effects of innervation on alpha-actin mRNA expression in regenerating muscle, nerveless, standard, and nerve-intact autografted muscles were examined. More complete innervation facilitated the recovery of alpha skeletal actin mRNA to control levels, but had little effect on the amount of alpha-cardiac actin mRNA. We found that regenerating muscle shows that embryonic pattern of alpha-actin mRNAs in the early stage and concluded that the recovery of alpha-skeletal actin mRNA expression to the adult pattern is influenced by innervation, while alpha-cardiac actin mRNA expression is nerve independent. PMID- 1511174 TI - Sense and antisense TGF beta 3 mRNA levels correlate with cardiac valve induction. AB - The formation of the valves in the heart is a spatially and temporally controlled process. A tissue interaction between the endothelium and its adjacent myocardium initiates the transformation of the endothelium into the mesenchymal precursors of the heart valve. One or more of the molecules implicated as critical for valve formation are members of the transforming growth factor beta family of molecules. Presented here is a spatial and temporal analysis of TGF beta 2 and TGF beta 3 in the chick heart during valve formation. We show that TGF beta 3 mRNA is concentrated in AV canal tissue where valve formation will occur, consistent with previous observations that TGF beta 3 production is critical during valve formation. Additionally, an RNA complementary to TGF beta 3 encoding mRNA is present in the heart. The temporally controlled appearance of RNA complementary to TGF beta 3 suggests that this molecule may play a role in the regulation of TGF beta 3 production in the heart. PMID- 1511175 TI - Differences in the histogenesis of EDL and diaphragm in rat. AB - We have examined the histogenesis of the diaphragm and extensor digitorum muscle in rat embryos, with the aim of defining differences in developmental patterns that can be related to the functional requirements of these muscles during and after development. Patterns of interactions between myotubes and other cells, and frequency of gap junctions are quite different in the two muscles. In diaphragm, primary myotubes (at day 16 in utero) are closely associated with each other, forming parallel sheets or palisades and communicating by gap junctions. Secondary myotubes have formed by day 18, but are immature, and the frequency of gap junctions is lower. The arrangement in palisades is maintained even after fibers are separated from each other by their individual basal lamina. In EDL primary fibers at day 16 have fewer gap junctions, and the peak in communication occurs after the appearance of secondary myotubes (day 18 and 21). Secondary myotubes are more mature than in diaphragm at day 18. PMID- 1511176 TI - Changes in dorsoventral but not rostrocaudal regionalization of the chick neural tube in the absence of cranial notochord, as revealed by expression of engrailed 2. AB - Notochord has been implicated in previous studies in both the dorsoventral and rostrocaudal patterning of the developing neural tube. This possibility has been further explored by analyzing the expression of Engrailed-2 in chick embryos developing with cranial notochord defects. Control embryos containing intact notochords expressed Engrailed-2 protein within the neural tube and in a subset of the neural crest and overlying surface ectoderm at the future mesencephalon and cranial metencephalon levels. Within the neural tube, expression was confined to cell nuclei in the roof plate and lateral walls; floor plate nuclei directly overlying the notochord typically failed to show expression. After surgical removal of Hensen's node, the source of notochord precursor cells, embryos were cultured through neurulation and assayed for expression of Engrailed-2 protein. All embryos that partially or completely lacked cranial notochord expressed Engrailed-2 in a pattern similar to that of control embryos containing intact notochords, except that when notochord and floor plate were absent, Engrailed-2 was also expressed in the most ventral part of the neural tube. These results indicate that 1) Engrailed-2 expression is suppressed in the most ventral neural tube owing to induction of the floor plate by the notochord, and 2) that the presence of an underlying notochord is not required for correct rostrocaudal expression, suggesting that multiple pathways act in the patterning of the rudiment of the central nervous system. PMID- 1511177 TI - Viruses and the blood. AB - Haematological syndromes attributed to viruses demonstrate geographical variations in incidence and great dependence on host factors. Severe haematological disease is the exception rather than the rule in dengue virus infection, and probably depends at least in part on the host immune response to the virus. The increased incidence of hepatitis-associated aplasia in east Asia may reflect distribution of an infectious agent, an environmental toxin, or genetic predisposition, but probably represents some combination of these factors. Agents with apparently universal distribution, such as parvovirus B19 and Epstein-Barr virus, are associated with bone marrow failure only in a very narrow range of hosts. These examples teach us that viral causes cannot automatically be excluded from the differential diagnosis of syndromes whose occurrence is rare or apparently sporadic. Further investigation of these syndromes should include more detailed characterization of host factors, particularly immunological characteristics, and possible infectious and toxic cofactors which are associated with morbidity. PMID- 1511178 TI - Anaemia of Plasmodium falciparum malaria. AB - The pathophysiology of the anaemia of falciparum malaria is both complex and multifactorial, and results in a condition which is a major cause of mortality and morbidity in patients, especially children and pregnant women, living in malarial endemic areas. The importance of anaemia as a cause of death in malaria may well be underestimated because of difficulty in diagnosis, especially where parasitaemia may be low and the clinical picture may be confused with other causes of anaemia. Two clinical presentations predominate: severe acute malaria in which anaemia supervenes, and severe anaemia in patients in whom there have been repeated attacks of malaria. The major mechanisms are those of red cell destruction and decreased red cell production. Potential causes of haemolysis include loss of infected cells by rupture or phagocytosis, removal of uninfected cells due to antibody sensitization or other physicochemical membrane changes, and increased reticuloendothelial activity, particularly in organs such as the spleen. Decreased production results from marrow hypoplasia seen in acute infections, and dyserythropoiesis, a morphological appearance, which in functional terms results in ineffective erythropoiesis. The role of parvovirus B19 as a possible cause of bone marrow aplasia in a few cases is postulated. Finally, there is now evidence which points to genetic factors, HLA associated, which may protect against the development of malarial anaemia and which has become common in areas endemic for malaria. PMID- 1511180 TI - Glucose-6-phosphate dehydrogenase deficiency. AB - Glucose-6-phosphate dehydrogenase (G6PD) deficiency is the most common human enzymopathy. Because its gene locus is on the X-chromosome it is more common in males than females in all populations. Prevalence rates vary from 62% among Kurdish Jews to the very low rates (0.1% or less in Japan, for example), which are compatible with sporadic cases arising from spontaneous mutations. However, there is at least one population in which G6PD deficiency has not been found, namely the indigenous (Amerindian) population of America. Approximately 400 variants have been described. Despite the clinical burden imposed by this enzymopathy, polymorphic frequencies have been reached in many populations. There is abundant epidemiological evidence that this has happened because of a biological advantage conferred on heterozygotes in falciparum malaria endemic areas. This advantage may apply to quartan malaria as well. Clinical severity varies, from the rare chronic nonspherocytic haemolytic anaemia to progressively milder forms like the Mediterranean and A- types. The other clinical syndromes, i.e. neonatal jaundice and haemolysis caused by infections, foods, drugs and chemicals, are not always predictable. This is because only a fraction of such enzymopathic persons develop these syndromes after exposure to the relevant stimulus. Modern techniques of molecular biology may elucidate why this is so. There is some emerging evidence that the genetic burden or survival value associated with G6PD deficiency may be relevant not only in tropical and infectious diseases, but also in their chemotherapy (e.g. malaria) as well as in the control of a long-recognized environmental pollutant such as lead. PMID- 1511179 TI - Genetic epidemiology of the beta s gene. AB - The beta s gene arose at least four times in Africa, with three of these mutations expanding through diverse ethnic groups, but limited to definite geographical areas: Atlantic west Africa for the Senegal haplotype linked beta s; central west Africa for the Benin haplotype; and equatorial, eastern and southern Africa for the Bantu haplotype. The fourth mutation (linked to the Cameroon haplotype) is restricted to a single ethnic group, the Eton of central Cameroon. The Benin haplotype linked beta s gene was spread by gene flow to the Mediterranean (north, south and east) and to the western portions of Saudi Arabia. An independent mutation linked to a fifth haplotype, Arab-India, is found among the tribals of India (independent from their geographical origin) and in the eastern oases of Saudi Arabia. It is also suspected of being associated with the beta s gene found in Afghanistan, Iran, Transcaucasia and central Asia. The selective force involved in the expansion of the gene was most likely P. falciparum malaria, and the time of the gene frequency increase was likely to have been during the expansion of agriculture about 4000 or more years ago in India and about 3000 years ago in Africa. The partial protection against severe and life-threatening malaria is through the limitation of P. falciparum parasitaemia. This is a complex process which involves at least two mechanisms: early intraerythrocyte parasite forms are in a suicidal position through increasing the tendency of HbAS cell to sickle and then be destroyed by the spleen; intraerythrocyte growth is inhibited during deep vascular schizogony. Although there is evidence that P. falciparum (and P. malariae) parasitaemias are limited in HbSS red cells, malaria is a major trigger to haemolytic and infarctive crises in sickle-cell disease, and a common cause of morbidity and mortality. PMID- 1511181 TI - Epidemiology of coagulation disorders. PMID- 1511182 TI - Platelets and platelet disorders in Africa. AB - Blood platelets, which are known to play important roles in normal vertebrate biology, are influenced by a variety of factors, the majority of which are acquired. In this chapter, attention is drawn to the need to re-examine one of the old accepted values in haematology, the normal platelet count. In addition, effects of some environmental factors, such as malarial parasitaemia, on both platelet count and platelet function are fully discussed. Similarly, the effects of HIV on platelets, as well as on other haematological parameters, in the African environment are described briefly. The urgent need is stressed for careful evaluation of the impact of HIV on the total disease burden in the population. In addition, the effect of environmental factors on the manifestations of some clinical features, e.g. splenomegaly and anaemia, in acute idiopathic thrombocytopenic purpura are highlighted. It is suggested that in such environments, the presence of these features do not constitute contraindications to making the diagnosis when other criteria are met. PMID- 1511183 TI - Onyalai. AB - Onyalai is an acquired form of immune thrombocytopenia which differs clinically, epidemiologically and immunologically from idiopathic thrombocytopenic purpura (Table 4). The clinical hallmark is haemorrhagic bullae on the mucosa of the oronasopharynx. Haemorrhage from ruptured bullae, epistaxis or gastrointestinal bleeding is severe and may cause shock and death. The disease is limited to some black populations of central southern Africa, with a recorded incidence of one per 660 inhabitants per year in the Kavango territory of Namibia. The majority of patients demonstrate both IgG and IgM serum platelet antibodies and serum platelet glycoprotein IIb/IIIa autoantibodies. Chronic thrombocytopenia often ensues and recurrent episodes of clinical bleeding are common. Treatment directed at the prevention of haemorrhagic shock reduced the mortality rate in the acute phase from 9.8 to 2.8%. Standard dose prednisolone does not increase the platelet count. Vincristine sulphate may benefit some patients and splenectomy is indicated in patients with severe uncontrollable haemorrhage. High dose intravenous gammaglobulin may be followed by a rise in the platelet count and cessation of haemorrhage. The aetiology is unknown. The possible aetiological role of mycotoxins from contaminated millet, sorghum or maize requires further investigation. PMID- 1511184 TI - Epidemiology of aplastic anaemia. PMID- 1511185 TI - Chromatin loops and transcriptional regulation. AB - The existence of a supermolecular structure in the eukaryotic nucleus, involving loops of chromatin attached at irregularly spaced points to the nuclear matrix, is now well established. Quite a bit is known concerning the DNA sequences involved in the attachment. However, the function of this highly organized structure remains largely unknown. In this review, we attempt to provide an overview of present knowledge of nuclear loop structure, and to critically summarize recent studies that provide new insights as to function. We derive the conclusion that the loop structure is very likely one in which DNA topology can be locally regulated by topoisomerase activity, and is most probably modified during development. PMID- 1511186 TI - c-myb and growth control. AB - The available evidence indicates that c-myb plays an important role in the proliferation of hematopoietic cells and in those nonhematopoietic cell types in which c-myb is expressed. A critical aspect in the regulation of c-myb expression rests in the positive autoregulatory mechanism, which is dependent on the interaction of myb protein with the 5' flanking region of the human c-myb gene. The positive autoregulation of c-myb, in conjunction with tissue-specific mechanisms that most likely involve efficient transcription beyond the site of "transcriptional pause" in the c-myb first intron, might allow the generation of c-myb transcripts at levels sufficiently high for optimal biological activity (e.g., at the G1/S transition of the cell cycle). Other transactivating factors, such as the Jun family members, also appear to be involved in regulating c-myb expression. Such factors might act to increase basal levels of c-myb expression to allow activation of the autoregulatory mechanism, or might cooperate with myb in transcriptional regulation of c-myb expression. The function of c-myb is ultimately dependent on the genes that are regulated by the myb product. Preliminary evidence suggests that DNA polymerase-alpha and cdc2, two genes that are critical for DNA synthesis, contain myb binding sites in their promoter region that appear to be required for myb transactivation of their expression. The paradox of the generality of the mechanisms by which c-myb affects cell proliferation and the apparent tissue-specific expression of this gene might be resolved by the growing evidence that the tissue distribution of c-myb is more general than previously appreciated, and that many cell types with no detectable c-myb expression contain a functional equivalent of this gene. For example, B-myb a gene that is homologous to c-myb in the DNA binding and transactivating domains and appears to be ubiquitously expressed, is also required for cell proliferation and, like c-myb, appears to regulate the expression of cdc2, a gene required for cell cycle progression. Together, these findings indicate a general role of members of the myb family in regulation of cell proliferation. PMID- 1511187 TI - Regulation of terminal deoxynucleotidyl transferase gene expression in mice and men. AB - A nontemplate directed DNA polymerase, terminal deoxynucleotidyl transferase (terminal transferase) is expressed in a tissue-specific and development stage specific manner. Its enzymatic properties and tissue localization have implicated the protein in development of normal immune function. Significant progress has been made in understanding the enzymology and important domains of this protein. More recently, studies have focused on regulation of the gene that codes for the protein in mice and humans. The murine gene has yielded to these studies more readily than the human gene. A murine basal promoter element has been identified along with several trans-acting protein factors that may regulate gene expression. In the human gene there is no evidence for a basal promoter element. Rather, the promoter exhibits tissue specific properties. The present article reviews recent developments in this field. PMID- 1511188 TI - Cell cycle regulation and the p53 tumor suppressor protein. AB - Somatic mutations of the p53 gene have been implicated as causal events in the formation of a large number of common human tumors. Several lines of evidence suggest that the nuclear phosphoprotein encoded for by the wild-type gene (wt p53) plays a role in regulating cell proliferation. Wt-p53 protein encodes a potent negative growth regulatory function that is lacking in mutant forms of the protein found in human tumors. In this review, the relationship between the expression of wt-p53 protein and cell proliferation is examined with emphasis on recent studies that provide clues as to the possible role that p53 plays in cell cycle regulation. A model for the action of p53 in regulating cell proliferation is proposed in which wt-p53 acts as a "checkpoint" protein to control the transit of cells through the restriction point in late G1-phase. After cells pass this "checkpoint" they become committed to enter S-phase and initiate DNA replication. This checkpoint function may be defective in cells that lack p53, express mutant p53, or in which the antiproliferative form of the protein is functionally inactive. Under these conditions stringent control of the initiation of DNA replication may no longer be possible, providing an environment conducive to the emergence oncogenic clones. PMID- 1511189 TI - Cytoarchitecture and signal transduction. PMID- 1511190 TI - Reference intervals and developmental changes in urinary prostanoid excretion in healthy newborns, infants and children. AB - Urinary excretion of prostaglandins E2, F2 alpha, E-M (7 alpha-hydroxy-5, 11 diketotetranor-prosta-1, 16-dioic acid), 6-keto F1 alpha, 2,3-dinor-6-keto-F1 alpha, thromboxane B2, 2,3-dinor-thromboxane B2 and 11-dehydrothromboxane B2 was determined by gas chromatography-mass spectrometry in 83 healthy subjects aged one day to 37 years. The excretion rates of all prostanoids increased with advancing age. After correction for 1.73 m2 body surface area, only urinary excretion rates of prostaglandins E-M and 6-keto-prostaglandin F1 alpha depended on age. Reference intervals were calculated as the 10th and 90th percentiles for prostaglandins E2 (4-27 ng/h/1.73 m2), F2 alpha (23-87 ng/h/1.73 m2), 2,3-dinor-6 keto-F1 alpha (4-19 ng/h/1.73 m2), thromboxane B2 (1-21 ng/h/1.73 m2), 2,3-dinor thromboxane B2 (8-36 ng/h/1.73 m2) and 11-dehydro-thromboxane B2 (15-87 ng/h/1.73 m2) in all subjects, and for prostaglandins E-M and 6-keto-prostaglandin F1 alpha in subjects aged 30 days or less (110-1140 ng/h/1.73 m2 and 7-23 ng/h/1.73 m2) and older than 30 days (62-482 ng/h/1.73 m2 and 2-12 ng/h/1.73 m2). High urinary excretion of prostaglandins E-M and 6-keto-F1 alpha during the newborn period and some distinct changes in urinary excretion of prostaglandin E2 and thromboxane B2 with advancing age suggest that these prostanoids might play a specific role during child development. PMID- 1511191 TI - Psychological development in children born with very low birth weight after severe intrauterine growth retardation: a 10-year follow-up study. AB - Children born small for gestational age (SGA) and children having very low birth weight, less than 1500 g, are claimed to be at risk of developmental problems, even when obvious pathology and disability are absent. In this study, sensorimotor and cognitive development of 14 medically healthy, very-low-birth weight and small-for-gestational-age children were investigated. The children were born at the Karolinska Hospital between 1979 and 1981. At the time of the assessment, the children were aged 8.7-11.2 years. The assessment instruments included the Wechsler Intelligence Scale for Children, a modified version of the Bruininks-Oseretsky Test of Motor Proficiency, as well as selected subtests from the Halstead-Reitan Neuropsychological Battery and from the Southern California Tests of Sensory Integration. Information was also obtained from obstetric, neonatal and pediatric records, which included early developmental assessments. As a control group, 14 children were recruited and matched for age, sex and socio economic background. The very-low-birth-weight-small-for-gestational-age group scored significantly lower on measures of visuospatial ability, non-verbal reasoning, strategy formation and gross-motor coordination. The group differences were largely attributable to the subnormal performance of eight of the very-low birth-weight-small-for-gestational-age children. These children, who also tended to be born earliest (less than 33 weeks), had a high incidence of behavioral and educational problems. These findings are consistent with the view that the very preterm infant develops a different neurobehavioral organization than a full-term infant. Developmental deficits may become increasingly evident in the early school years. PMID- 1511192 TI - Fluid restriction for preventing bronchopulmonary dysplasia? Reduced fluid intake during the first weeks of life improves the outcome of low-birth-weight infants. AB - One hundred consecutive low-birth-weight infants (less than 1751 g) were randomized equally into "dry" and "control" groups. Fluid administration in the dry group followed the schema 50, 60, 70, 80, 90, 100 and 120 ml/kg/day during the first week and 150 ml/kg/day until aged four weeks and that of the control group 80, 100, 120 and 150 ml/kg/day during the first week and 200 ml/kg afterwards. The diagnosis of bronchopulmonary dysplasia was based on typical roentgenographic findings, clinical symptoms and a supplemental oxygen requirement at age one month. Mean weight loss was greater in the dry group than in the control group (8.8 vs 6.2%), but there was no difference in weight between the groups at the age of four weeks. Twelve of the patients died, one in the dry group and 11 in the control group (five died during the first 24 h and the remaining six between three days and three months). Twenty-seven subjects in the dry group and 15 in the control group were alive and had no signs of bronchopulmonary dysplasia at age 28 days (p less than 0.05), the numbers at term being 28 and 14, respectively (p less than 0.01). These results suggest that fluid restrictions can reduce the mortality and morbidity of low-birth-weight infants. Infants of this kind, with respiratory distress, show poor tolerance to fluids, especially during the first weeks of life. PMID- 1511193 TI - Treatment with hypertonic dextrose and insulin in severe hyperkalaemia of immature infants. AB - Over a three-year period, 12 infants received dextrose/insulin infusions for severe hyperkalaemia from a mean age of 24 h. The infants were born after 24 to 26 weeks of gestation and weighed 730 +/- 172 g (mean +/- SD) at birth. Serum potassium concentration ranged from 7.4 to 8.4 mmol/l (7.7 +/- 0.4 mmol/l; mean +/- SD). Four had cardiac arrhythmias. All infants showed an initial response, serum potassium concentration decreased below 6.5 mmol/l in 5 +/- 2 h. In two infants, rebound hyperkalaemia occurred and was resistant to treatment; both infants died, one during an exchange transfusion. In the other 10 infants, infusions were ceased at a mean postnatal age of 53 h. Hyperglycaemia was the major problem during infusion and was resistant to increases in insulin concentrations. Normoglycaemia was achieved in 10 infants. The hypertonic solution consisted of a dextrose/insulin ratio of 2.2 +/- 0.6 g/IU, which delivered glucose at a rate of 0.46 +/- 0.15 g/kg/h, in addition to the pre existing stable maintenance glucose intake. PMID- 1511194 TI - Pneumonia and pneumonitis in childhood malignancy. AB - We conducted a survey over a 21-year period of the incidence and risk of occurrence of episodes of pneumonia and pneumonitis in children treated for solid tumours and leukaemia. One hundred episodes occurred amongst 219 patients, seven of which were associated with death. Focal opacification on the chest radiograph was more common than diffuse opacification. Patients with leukaemia had a significantly higher rate of occurrence of pneumonia and pneumonitis during the periods of induction and maintenance compared with the off-treatment period, and during the relapse period compared with the period of maintenance. Patients with solid tumours had a significantly higher rate of occurrence during treatment compared to the off-treatment period. The rate of occurrence on treatment was the same in patients with solid tumours and acute leukaemia. Children with malignancy have a high incidence of pneumonia and pneumonitis and death is rare if the patient does not have terminal malignant disease. PMID- 1511195 TI - Modification of some markers of inflammation during treatment for acute respiratory exacerbation in cystic fibrosis. AB - An objective approach for monitoring the treatment of acute pulmonary exacerbation in cystic fibrosis was evaluated. Eleven biochemical markers of inflammation (erythrocyte sedimentation rate, neutrophil count, C-reactive protein, alpha-1 antitrypsin, haptoglobin, ceruloplasmin, fibronectin, alpha-1 glycoprotein, alpha-2 macroglobulin, C3, granulocyte elastase and anti Pseudomonas IgG) were measured in blood serum and plasma from 46 cystic fibrosis patients with chronic Pseudomonas aeruginosa colonization before and after treatment. The overall outcome in each patient was evaluated by means of a pondered sum of clinical, chest X-ray and lung function scores. Biochemical markers were related to the overall clinical improvement: haptoglobin, ceruloplasmin, fibronectin and alpha-1 glycoprotein showed a good sensitivity (64 70%), specificity (60-70%) and positive predictive value (86-89%). Granulocyte elastase showed a similar sensitivity (67%) and positive predictive value (85%) but a lower specificity (33%). The negative predictive value was generally poor (32-39%). Our data suggest that the combined measurement of some markers of inflammation and of conventional clinical parameters, may help in evaluating the efficacy of anti-infective treatment in cystic fibrosis. PMID- 1511196 TI - Tracheostomy in pediatric patients. AB - From 1978 to 1987, tracheostomy was performed on 33 children, 13 boys and 20 girls, with a male to female ratio of 0.65:1. The mean age at the time of tracheostomy was 726 days, 76% of the children being under the age of two years. The incidence of pediatric tracheostomy per hospital admissions was 0.05%. Subglottic stenosis (13 children) and respiratory distress syndrome with prolonged endotracheal ventilation (11 children) were the most common indications for tracheostomy. The mean duration of prolonged endotracheal intubation before tracheostomy was 64 days, and that of tracheostomy treatment 117 days. During the tracheostomy period, five children died, but only one death was related to tracheostomy. The total rate of complications was 30%. We emphasize the importance of strict indications for pediatric tracheostomy. PMID- 1511197 TI - Late sequelae of gonadal, mediastinal and oral teratomas in childhood. AB - Thirty-two patients with gonadal or non-sacrococcygeal extragonadal teratomas who underwent operation in childhood were evaluated for different late sequelae. Follow-up times ranged from 5.0 to 40 years. Physical abnormalities resulting from surgery were seen in eight patients who had had oral or mediastinal primary teratomas. Radiographs revealed multiple spina bifida occulta lesions in three patients. The males, but not the females, showed signs of gonadal dysfunction. Impaired semen quality or abnormal serum concentrations of testosterone or gonadotrophins were found in five of 10 adult men who had had testicular or mediastinal teratomas. Thus, some late sequelae may be predicted from the site of the primary teratoma, but gonadal dysfunction in males and vertebral anomalies may occur irrespective of where the teratoma is situated. PMID- 1511198 TI - Metabolic control and diet in Finnish diabetic adolescents. AB - The effects of dietary, clinical and demographic factors on metabolic control in 105 diabetic adolescents were studied. All patients had diabetes for longer than two years and a daily insulin dose greater than 0.5 IU/kg body weight. Low body mass index, high social class, high number of daily eating occasions, high day-to day variation in energy intake, high number of urine tests and a long interval between insulin injection and eating were associated with good metabolic control. Many of these determinants reflect also the general compliance with the diabetic regimen. The results stress the importance of good coordination between insulin injections and eating habits. PMID- 1511200 TI - Doppler echocardiographic and morphologic evaluation of patients following operative repair of aortic coarctation. AB - Sixty-six patients operated on previously for coarctation of the aorta were included in the study. There were 50 children and 16 adults. Invasive and non invasive gradients were recorded. Anatomical obstruction was evaluated by angiography in 54 patients and the numbers and size of collaterals were quantified. The closest correlation was found between Doppler-estimated gradients and invasive peak-instantaneous gradients (r = 0.87). The relation between anatomical obstruction and invasive peak-to-peak gradients, Doppler gradients and diastolic flow ere discouraging (r = 0.64, 0.54 and 0.35). Liberal indications for angiography or magnetic resonance tomography are recommended. PMID- 1511199 TI - A single pediatric center experience with 1025 children with hypertension. AB - Between January 1982 and December 1989 1025 patients aged between one month and 18 years with increased blood pressure were referred for evaluation. Borderline hypertension was found in 389 children; 636 had sustained significant hypertension. In 351 patients, hypertension was secondary to a known disease. Renal parenchymal diseases were present in 68% of patients while renovascular and endocrine disorders were found in 10% and 11%, respectively. Of the 258 children aged less than 15 years, all but six children had known causes of hypertension, while 75% of adolescents had essential hypertension. In the 389 children with borderline hypertension, 65% developed fixed hypertension over a period of 2-3 years. PMID- 1511201 TI - Medical vocational guidance for adolescents--is it effective? AB - The outcome of school medical vocational guidance was studied in all 1595 students enrolled in 1987 in grade 9 in the primary schools of Linkoping. In grade 9, the school health service had listed 249 students with a chronic disorder. These were sent a questionnaire which was answered by 235 students. Only 5/235 stated that vocational information from physicians and school nurses had been important for their choice of career. No more than 22/235 had chosen a medically ill-suited secondary school study course. This figure is close to the number expected, assuming that all choices of study courses are at random. At follow-up in May 1989, no one said that they had changed study course or work due to their medical disorder. Thus, school medical vocational guidance seems to have little effect on the vocational choices of adolescents with chronic disorders. PMID- 1511202 TI - Health examination of preschool children in relation to school adjustment in grade I. AB - The results of a collaborative study on health examination in preschool children, using data from child health care, preschool establishments and a teacher evaluation carried out six months after the start of school were compared. The analysis showed that many children with difficulties in motor function, behaviour and/or learning in grade 1 had been identified at the health examination. The results emphasize the value of collaboration between preschool establishments, child health care centres and schools for identification of children at risk of developing early adjustment problems. PMID- 1511203 TI - Cystic fibrosis mutations in southern Sweden: relationship to clinical severity. PMID- 1511204 TI - Prediction equations for total body water during early infancy. PMID- 1511205 TI - Colostrum and human milk inhibit localized adherence of enteropathogenic Escherichia coli to HeLa cells. PMID- 1511206 TI - Dinamap blood pressure measurements in the newborn: how many--what effects? PMID- 1511207 TI - Thyroid dyshormonogenesis: severe hypothyroidism after normal neonatal thyroid stimulating hormone screening. AB - We report four children who presented no evidence of primary hypothyroidism in the neonatal period, either clinically (normal growth velocity) or biochemically (normal plasma levels of thyroid stimulating hormone and/or thyroid hormone). However, in early childhood, these children developed severe hypothyroidism due to dyshormonogenesis. We conclude that apparently normal thyroid function in the neonatal period does not preclude the development of severe hypothyroidism due to thyroid dyshormonogenesis later in childhood. PMID- 1511208 TI - The value of peritoneal dialysis in the treatment of severe ethanol intoxication in childhood revised. AB - We treated a girl aged 3.5 years (15 kg) with ethanol intoxication, using peritoneal dialysis. The blood ethanol concentration was 6.4 g/l (640 mg/dl; 138.9 mmol/l). It was calculated that the child drank a total amount of 67.2 g of ethanol (4.5 g/kg). The spontaneous ethanol elimination rate before peritoneal dialysis was 0.27 g/l (5.86 mmol/l) per hour; during peritoneal dialysis we found an ethanol elimination rate of 0.32 g/l (6.94 mmol/l) per hour, which was lower than expected. In childhood the ethanol elimination rate with peritoneal dialysis is only slightly faster in comparison to the high spontaneous elimination rate. We conclude that treatment of severe ethanol intoxication should include mainly the maintenance of the vital functions and the meticulous control of blood sugar levels and acid-base disturbances, especially in children. Indications for dialysis are complications caused by ethanol and resistant to supportive therapy, such as seizures, metabolic disturbances, persistent hypoglycemia and the possibility of combined intoxication with other dialysable drugs. PMID- 1511209 TI - No association between HLA-DR2 and the sudden infant death syndrome. PMID- 1511210 TI - [Therapeutic embolization of pulmonary arteriovenous malformations]. AB - It is reported on the practicability and the results of therapeutic embolizations in 7 patients with pulmonary av-malformations. The embolizations were carried out by detachable balloons. In all cases there were immediate and well-defined occlusions. In direct fistulas the embolization represents a curative procedure. However, in cases of angiomatous malformations with slow flow character, only a reduction of shunt or decreasing of size is obtained. PMID- 1511211 TI - [Internal carotid artery aneurysm in the petrous canal]. AB - Internal carotid aneurysm in the petrous canal are rarely observed. According to our knowledge there are only 24 reported cases. We present the case of a 47-year old woman. The clinical, radiological and histological findings are discussed. PMID- 1511212 TI - [Magnetic resonance tomography: value and limits in gastroenterologic diagnosis]. AB - At present, the value and limitations of magnetic resonance imaging (MRI) as a diagnostic modality in gastroenterology cannot be conclusively determined. MRI has a high sensitivity in the detection of focal liver lesions. The signal intensity of focal liver lesions on plain and contrast-enhanced T1-weighted images and on plain T2-weighted scans narrows the differential diagnosis in many cases. Imaging of the gallbladder and pancreas presently is no indication for MRI. The high sensitivity of MRI in the detection of fistulae and abscesses in Crohn's disease and the differentiation from fibrosis represents an advantage over other modalities in imaging of inflammatory bowel disease. MRI is superior to CT in differentiating recurrent rectal cancer from fibrosis. Further development of MRI and the use of contrast media for both oral and intravenous administration may offer new perspectives of MRI in the diagnosis of diseases in gastroenterology. PMID- 1511213 TI - [Controlled percutaneous puncture of gastrointestinal and hepatopancreatic lesions. An overview]. AB - The cross sectional imaging of ultrasonography and computed tomography provides information for the puncture of focal lesions and fluid collections and additional drainage if necessary. A survey is given of the predispositions, technical aspects, results and complications of both methods. PMID- 1511214 TI - [Endosonography in malignant extrahepatic obstructive jaundice]. AB - 34 patients with obstructive jaundice were investigated consecutively by transcutaneous ultrasonography, endoscopic sonography and endoscopic retrograde cholangio-pancreatography (ERCP). In 20 cases obstruction was due to a tumor, whose location and extent could be visualized by endosonography and ERCP in all cases. By transcutaneous ultrasonography this was possible in only 14 (70%) and 17 (85%) cases respectively. In seven of eight cases the tumor size, in four of five cases metastatic involvement of lymph nodes and in all cases infiltration into neighboring organs or vessels were correctly predicted by endosonography. Both other methods failed in this regard. We therefore conclude that the diagnostic information obtained by endosonography in patients with obstructive jaundice due to malignancy is superior to conventional sonography and ERCP. PMID- 1511215 TI - [Splenic size and duplex sonography determination of blood flow in the vena lienalis and vena portae in liver cirrhosis]. AB - Splenomegaly is a common finding in patients with portal hypertension. In the present study the relation between spleen size and blood flow in the splenic and portal vein was evaluated in 33 patients with alcoholic liver cirrhosis and portal hypertension using pulsed Doppler sonography (Ultramark 9, ATL, Solingen, FRG). There was a significant positive correlation between hilar spleen diameter (HD) and splenic vein diameter (r = .73, p less than .001) as expected as the consequence of portal hypertension. However, a positive correlation between HD and splenic vein flow (SBF) was found (r = .67, p less than .001). Furthermore, there was no negative correlation between HD and flow velocity in the splenic vein (r = .01, n.s.). Portal blood flow (830 +/- 360 ml/min) was fairly constant in spite of considerable variations in SBF (range: 120 to 1200 ml/min). The data of the present study indicate that splenomegaly in patients with liver cirrhosis and portal hypertension is not simply the consequence of portal congestion resulting in decreased SBF. Rather, increased SBF serves to maintain portal blood flow and thereby contributes to portal hypertension. In few patients (15%) SBF increased to more than 11/min may be an important factor for the severity of portal hypertension. Surgical shunt treatment should be adjusted in these patients. PMID- 1511216 TI - [Extracorporeal shock wave lithotripsy in patients with bile duct calculi]. AB - 21 patients with choledocholithiasis, in whom methods such as endoscopy or mechanical lithotripsy were unsuccessful, extracorporeal shock wave lithotripsy was performed. Fragmentation could be achieved in 90%, complete stone clearance after endoscopic stone extraction occurred in 76%. Extracorporeal shock wave lithotripsy has proven highly effective with a low complication rate and zero lethality. Therefore, its role in the management of gall stone disease in the elderly patient at high perioperative risk cannot be overemphasized. PMID- 1511217 TI - [Simultaneous sonographic study of postprandial gastric emptying and gallbladder contraction]. AB - Postprandial gastric emptying and gallbladder contraction were assessed in 14 healthy subjects by means of ultrasonography after oral administration of a semi liquid test meal (250 ml, 1450 kJ). For this purpose, cross-sectional areas of the gastric antrum and gallbladder volume were calculated and recorded over a period of 120 minutes using an annular-array-transducer. The semi-liquid test meal allowed suitable sonographic measurement of cross-sectional areas of the antrum in all 14 subjects. Mean half-time of gastric emptying was 47 minutes (range 17-72 minutes). Mean peak gallbladder contraction was 36% (range 17-60%) of initial volume and mean time to peak contraction was 65 minutes (range 20-120 minutes). The method described was found to be a practical and reliable procedure for the investigation of postprandial gastric emptying and gallbladder contraction. It is therefore of potential interest for application to a variety of clinical questions. A minor drawback involves the relative length and variability of time required for testing, owing to the wide range in the time course of gastric emptying and gallbladder contraction across subjects. Normal ranges for defined test meals must be established in large control groups. PMID- 1511218 TI - The importance of MRI (magnetic resonance imaging) for the diagnosis of brainstem infarction. AB - As experience with it accumulates, high resolution MRI seems more capable of representing morphological alterations of the central nervous system than cranial computer tomography (CCT). The question thus arises whether the detection of brainstem infarctions with MRI might not be easier than with CCT and how the topography of brainstem lesions demonstrated with MRI correlate with clinical symptoms and signs. 16 patients with definite clinical symptoms of brainstem infarction were examined by MRI. The examination took place between the 10th and 14th day after the occurrence of the infarction. Using MRI, we found pathological results in only 8 of these cases. In only 5 of these cases a clear relationship between the neurological picture and the topography of the lesion could be shown. These findings demonstrate that despite the high quality of the MRI images, the clinical examination for symptoms and signs is more important than imaging in the brainstem infarction. PMID- 1511219 TI - Comparison of MRI, CT and angiography in cerebral arteriovenous malformations. AB - Computed tomography (CT), magnetic resonance imaging (MRI) and cerebral angiography were performed in 30 patients with cerebral arteriovenous malformations (AVMs). Clinical data and radiographic findings are presented. The diagnostic values of CT and MRI are compared. 25 of 30 AVMs were seen on CT scans, 27 on MR-images, 26 by angiography. Typical CT-findings were irregularly hyperdense areas with spotlike contrast enhancement. 4 out of 5 AVMs not depicted by CT were diagnosed for tumor, in one case the malformation was hidden by a hematoma. MRI mostly showed the AVM as round or oval lesions with spongelike structure of low signal intensity in T1-weighted sequences or as single enlarged vessels. The 26 AVM revealed by angiography presented typically enlarged vessels; in 2 cases angiography was without any pathological findings, 2 cases showed signs of a space occupying lesion. The results confirm that MRI is superior to CT in detecting and recognizing AVM. Its strength lies in the possibility to detect abnormal vessels even in presence of fresh or older hematoma, and in the precise information on size and location of the AVM. In our series, MRI and CT-scans together showed 28 of 30 AVMs, the remaining 2 cases were not seen with angiography either but only proven histologically. Although today MR-angiography is able to provide three dimensional images of blood vessels, it cannot yet replace angiography in the exact study of the vessels which is required for surgical planning. PMID- 1511220 TI - Expansion of the cortical representation of a specific skin field in primary somatosensory cortex by intracortical microstimulation. AB - Intracortical microstimulation (ICMS) was applied to a single site in the middle cortical layers (III-IV) in the koniocortical somatosensory fields of sodium pentobarbital-anesthetized rats (Sml) and new world monkeys (area 3b). Low threshold cutaneous receptive fields were defined in the cortical region surrounding the stimulation site prior to and following 2-6 hr of 5 microA ICMS stimulation. ICMS stimulation did not usually affect the receptive field location, size, or responsiveness to tactile stimulation of neurons at the stimulation site. However, the number of cortical neurons surrounding the stimulation site with a receptive field that overlapped with the ICMS-site receptive field increased in all studied animals, resulting in an enlarged cortical representation of a restricted skin region spanning several hundred microns. The mean size of receptive fields changed in some but not all cases. These results provide evidence that the responses of cortical neurons are subject to change by the introduction of locally coincident inputs into a single location, and demonstrate a capacity for representational plasticity in the neocortex in the absence of peripheral stimulation. These experimental observations are consistent with hypotheses that the cerebral cortex comprises radially oriented populations of neurons that share a common input, and that these inputs are shaped by coincident activity (see Edelman, 1978, 1987; Merzenich, 1987; Merzenich et al., 1990; von der Malsburg and Singer, 1988). PMID- 1511221 TI - Characteristics of intracellularly injected infragranular pyramidal neurons in cat primary auditory cortex. AB - Pyramidal neurons in layers V and VI of cat primary auditory cortex (AI) were intracellularly injected with biocytin after functional characterization according to a position relative to an anteroposterior sequence of best-frequency responses. A sample of 19 completely filled neurons was analyzed, and a preliminary classification was made on the basis of dendritic morphology and axon collateral distribution. Layer V cells could be divided into two types. Cells in the upper part of layer V and projecting toward the diencephalon had a large cell body and an apical dendrite with extensive branches in layer I. These cells had few recurrent axon collaterals, and no terminal axonal bushes were formed in the vicinity of the dendritic field. Long horizontal collaterals with many boutons, however, extended in various directions parallel to the cortical surface. By contrast, cells in the lower part of layer V and sending an axon into the putamen, or without an obvious subcortical axon, had a medium soma and an apical dendrite with few branches in layer I. These cells had a dense bush of recurrent collaterals extending into layers II and III and surrounding the dendritic field, but few or no horizontal collaterals. Layer VI injected neurons were more heterogeneous. All had a thin ascending dendrite with oblique branches both ending in layer III. Axon collateral distributions varied from cell to cell. Relatively small cells with an apical dendrite that branched frequently in layers III and IV had a dense network of recurrent collaterals in the dendritic field, but virtually no horizontal collaterals. This type projected toward the diencephalon. Cells with relatively long horizontal collaterals and a weak recurrent system confined to layers V and VI had a unique arborization pattern of basal dendrites. This type may have projected to the claustrum or other cortical areas. One cell with dendritic branches restricted to layer VI had horizontal collaterals predominantly in layer VI. This cell projected into the corpus callosum. The apparent close correlation between extrinsic projections of infragranular neurons and their dendritic morphology and intracortical collateral distributions suggests that differentially projecting cells may engage different elements of intracortical circuitry in AI. PMID- 1511222 TI - The spatial distribution of pulvinar neurons that project to two subregions of the inferior parietal lobule in the macaque. AB - The distribution of pulvinar neurons that project to the lateral intraparietal area (LIP) and area 7a, two subregions of the inferior parietal lobule in monkeys, was determined using small injections of retrogradely transported fluorescent dyes. Both LIP and 7a received the majority of their thalamic input from contiguous but distinct zones within the medial pulvinar nucleus. Thalamocortical cell bodies that projected to LIP were arranged in a dense, horizontally oriented cluster that was sandwiched between two similar clusters of neurons that projected to 7a. There was minimal overlap of the respective clusters. LIP also received an appreciable input from the dorsal half of the lateral pulvinar nucleus, but tracer placements in 7a resulted in only occasional labeled neurons in the lateral pulvinar. PMID- 1511223 TI - Fractionating language: different neural subsystems with different sensitive periods. AB - Theoretical considerations and psycholinguistic studies have alternatively provided criticism and support for the proposal that semantic and grammatical functions are distinct subprocesses within the language domain. Neurobiological evidence concerning this hypothesis was sought by (1) comparing, in normal adults, event-related brain potentials (ERPs) elicited by words that provide primarily semantic information (open class) and grammatical information (closed class) and (2) comparing the effects of the altered early language experience of congenitally deaf subjects on ERPs to open and closed class words. In normal hearing adults, the different word types elicited qualitatively different ERPs that were compatible with the hypothesized different roles of the word classes in language processing. In addition, whereas ERP indices of semantic processing were virtually identical in deaf and hearing subjects, those linked to grammatical processes were markedly different in deaf and hearing subjects. The results suggest that nonidentical neural systems with different developmental vulnerabilities mediate these different aspects of language. More generally, these results provide neurobiological support for the distinction between semantic and grammatical functions. PMID- 1511224 TI - Entropy and cortical activity: information theory and PET findings. AB - Functional segregation requires convergence and divergence of neuroanatomical connections. Furthermore, the nature of functional segregation suggests that (1) signals in convergent afferents are correlated and (2) signals in divergent efferents are uncorrelated. The aim of this article is to show that this arrangement can be predicted mathematically, using information theory and an idealized model of cortical processing. In theory, the existence of bifurcating axons limits the number of independent output channels from any small cortical region, relative to the number of inputs. An information theoretic analysis of this special (high input:output ratio) constraint indicates that the maximal transfer of information between inputs, to a cortical region, and its outputs will occur when (1) extrinsic connectivity to the area is organized such that the entropy of neural activity in afferents is optimally low and (2) connectivity intrinsic to the region is arranged to maximize the entropy measured at the initial segments of projection neurons. Under the constraints of the model, a low entropy is synonymous with high correlations between axonal firing rates (and vice versa). Consequently this antisymmetric arrangement of functional activity in convergent and divergent connections underlying functional segregation is exactly that predicted by the principle of maximum preservation of information, considered in the context of axonal bifurcation. The hypothesis that firing in convergent afferents is correlated (has low entropy) and spatially coherent was tested using positron emission tomographic measurements of cortical synaptic function in man. This hypothesis was confirmed. PMID- 1511225 TI - Warning: the alcohol industry is not your friend? PMID- 1511226 TI - Ideology, history and changing models of liver cirrhosis epidemiology. AB - This analysis describes changes in assumptions about beverage alcohol use as a major cause of liver cirrhosis since the turn of the century. The findings reveal that social and political views shaped by the temperance movement, Repeal era and modern alcoholism movement have had a profound impact on medical and public health interpretations of the role of alcohol use in liver disease. Current clinical and epidemiological approaches that stress the importance of alcohol as a direct etiological agent for liver cirrhosis were popular during the 19th century in the wake of the temperance and prohibition movements, but were greatly modified to attribute a secondary role to alcohol use as a cause of cirrhosis during the Repeal and post-World War II eras. The changes during the Repeal and post-World War II eras coincided with the expansion of alcohol consumption and the liberalization of drinking norms in US society. As a result, the role of alcohol in causing cirrhosis among the general population was minimized and the disease was attributed to industrial toxins and air pollution. Contemporary research has affirmed the importance of beverage alcohol as a causal agent of liver cirrhosis using both clinical and epidemiological studies. PMID- 1511227 TI - Classical conditioning and cognitive determinants of subjective craving for opiates: an investigation of their relative contributions. AB - Subjective craving for drugs is frequently reported by detoxified addicts. Explanatory models emphasizing classical conditioning (CC) and cognitive mechanisms have been proposed, and the mechanisms postulated by the two approaches are discussed here. There are three major variants of the CC model, arguing that craving is associated with conditioned changes which are respectively drug-agonistic, opponent-process, or withdrawal reactions. The cognitive model highlights the role of 'outcome expectancies' as determinants of both appetitive and avoidant motivations. The present investigation has identified correlates of craving predicted by the above models, and tested them empirically. Detoxified opiate addicts participated in in a Craving Test requiring them to rate their craving, physical state, and emotions during exposures to both neutral and drug-related material. Other measures, including personality and outcome expectancies for drug use, were also taken, and interrelationships among the variables were explored statistically. Whilst some of the predictions of the CC formulations were borne out, the cognitive model received more consistent support. The theoretical and treatment implications of these data are considered. PMID- 1511228 TI - Hypercortisolism after opioid discontinuation in rapid detoxification of heroin addicts. AB - Long-term opioid consumption can induce hypoadrenalism through impairment of the hypothalamic-pituitary-adrenal axis. Results of the present study showed that, in heroin addicts, saliva cortisol concentrations varied according to the amount of recently consumed heroin and the time elapsed since the last self-administration. Hypercortisolism was observed either after abrupt withdrawal of heroin or the last dose of methadone. Post-detoxification hypercortisolism was still present on day 16 after the last opioid consumption, whereas it was not observed in abstinent addicts for a mean period of 4 months. During detoxification treatment, mean AUC8-24 cortisol in saliva of clonidine or guanfacine-treated patients was significantly higher than that in methadone-treated patients. It may be hypothesized that elevated cortisol levels may account for untoward effects of adrenergic agonist therapy which, in turn, may represent an added risk factor for relapse during detoxification. Further studies are necessary to correlate the severity of withdrawal symptoms to cortisol levels in opioid addicts detoxified with alpha 2-adrenergic agonist substitution. PMID- 1511229 TI - Patterns of drug use in Castille and Leon (Spain). AB - A total of 2500 individuals, aged 14-70 years and living in Castille and Leon (Spain), were surveyed in the spring of 1989 with regard to their drug consumption and patterns of use. 'Lifetime' drug users' rates were 30.0% for cannabis, 5.4% for cocaine, 5.2% for amphetamines, 2.4% for psychedelic drugs, 1.5% for opiates, 1.1% for tranquillizers, and 0.4% for inhalants. 'Regular' drug users were more common among cannabis--2.8% of the surveyed--and less frequent among cocaine, opiates and amphetamine users--0.3% of everyone of the substances mentioned above. 'Lifetime' drug users were more common among males than among females, among singles than among married, in those younger (18-29 years of age) and with work problems. The starting age of drug consumption ranged between the average of 15.6 years of age for those who consumed inhalants and 19.5 for those who consumed cocaine. The results allow a better understanding of the pattern of drug use in Castille and Leon (Spain), as well as the 'high' prevalence of drug use in our region. PMID- 1511230 TI - The relationship between stressful working conditions and high alcohol consumption and severe alcohol problems in an urban general population. AB - The relationship between 15 measures of stressful working conditions and high alcohol consumption (35 g 100% ethanol per day or more for men and 25 g or more for women) was studied, using cross-sectional data from a general population survey of 1344 males and 1494 females; the ages 25-64 years in metropolitan Stockholm in 1984. In a longitudinal component of the study, hospitalization and mortality with alcohol-related diagnosis was assessed during 1984-90, and also the association between previous experience of unemployment and high alcohol consumption. Some of the associations, expressed as age-adjusted odds ratios, were positive and some were negative when high alcohol consumption was the endpoint, but there was a clear variation by sex and social class. Generally the positive associations were stronger among male non-manual employees. Among males, there was a clear association between stressful working conditions and subsequent risk of severe medical alcohol-related problems, but the precision of the estimates was low due to low number of cases. The odds ratio was 6.18 (95% confidence interval 1.86, 20.61) for twisted working positions and 6.74 (95% confidence interval 1.67, 27.19). Previous unemployment among males was associated with increased risk for high alcohol consumption, with an odds ratio of 5.71 (95% CI 1.39, 15.97) among those who had been unemployed more than once, and 1.67 (95% CI 0.76, 3.64) among those who had been unemployed once during the previous 5 years. Those and other increased odds ratios were lower when subjects with an alcohol diagnosis at inpatient care during 1980-84 were excluded in the analyses. On the whole, our findings are not conclusive. The strong, but imprecise associations between stressful working conditions and severe alcohol problems, are however challenging, and warrants further studies, preferably with longitudinal design and repeated measurements of both working condition and alcohol habits. PMID- 1511231 TI - Smoking habits in relapsed subjects from a smoking cessation trial after one year. AB - Reports of smoking cessation studies often claim that many relapsed subjects reduce their smoking. We investigated the smoking habits of relapsers 1 year after quitting in a smoking cessation trial using nicotine or placebo patches. All 289 participants in that study were summoned to a 1-year follow-up visit--148 (57%) of 259 relapsers attended, as did all 30 sustained abstainers. Fewer than 1% of the subjects had quit spontaneously after the primary relapse. Daily cigarette consumption, standard nicotine yield per cigarette, saliva cotinine concentration, expired carbon monoxide level and two nicotine dependency scales were assessed at entry and at the 1-year follow-up. In five of these six smoking related characteristics, there was a small but significant mean reduction of 7% 27%. A significant weight gain of 0.5 +/- 2.9 kg (mean +/- SD) was recorded in the relapsers compared with 4.8 +/- 4.2 kg for abstainers (p less than 0.001). It is concluded that smoking habits in relapsers are relatively unchanged, and thus the most important outcome measure in smoking cessation trials is abstinent subjects. PMID- 1511232 TI - Can carrots be addictive? An extraordinary form of drug dependence. AB - The paper describes three cases of dependence on carotenoids with typical symptoms of irritability and nervousness accompanying their abstinence, with a long-term dependence, and an inability to simply discontinue. Three patients (a man and two women) all being smokers, evaluated this dependence as very similar to that on tobacco. The limitation of further use had the same effect in both cases. The women evaluate the dependence as stronger than that on cigarettes, the man as somewhat weaker. The former patient--a woman--even relapsed, and recently found herself in danger of further relapse. This, however, she nipped in the bud. Laboratory enzyme examinations revealed a disorder in the enzymatic outfit affecting the auto-immunity and the neurovegetative system. PMID- 1511233 TI - Early onset of drinking as a risk factor for lifetime alcohol-related problems. AB - Heavy drinking among students has been a major public health concern over the past decade. A nationally representative 1988 survey on drinking practices and related problems examined the effect of age of of onset of drinking on lifetime alcohol-related problems. Prevalence estimates were obtained for major demographic subgroups of the population. Results and implications are discussed in the context of minimum legal drinking age. PMID- 1511234 TI - Female Chinese problem drinkers. PMID- 1511235 TI - Dynamic properties of salmon calcitonin bound to sodium dodecyl sulfate micelles: a restrained molecular dynamics study from NMR data. AB - We have investigated the conformational behaviour of salmon calcitonin bound to sodium dodecyl sulfate micelles by means of restrained molecular dynamics simulations with both 'static' and time-averaged NMR distance restraints. A more realistic picture of the inherent flexibility of the hormone is obtained when using time averaging. With this approach, long-range NOEs are interpreted better by considering a dynamical exchange among different conformations. PMID- 1511236 TI - Spatial structure of (34-65)bacterioopsin polypeptide in SDS micelles determined from nuclear magnetic resonance data. AB - The spatial structure of a synthetic 32-residue polypeptide, an analog of the membrane-spanning segment B (residues 34-65) of bacterioopsin of Halobacterium halobium, incorporated into perdeuterated sodium dodecyl sulfate micelles, was determined from 1H NMR data. The structure determination included the following steps: (1) local structure analysis; (2) structure calculations using the distance geometry program DIANA; (3) systematic search for energetically allowed side-chain rotamers consistent with NOESY cross-peak volumes; (4) random generation of peptide conformations in allowed conformational space. The obtained structure has a right-handed alpha-helical region from Lys41 to Leu62 with a kink of 27 degrees at Pro50. The C-cap Gly63 adopts a conformation with phi = 87 +/- 6 degrees, psi = 43 +/- 10 degrees typical to a left-handed helix. The N-terminal part (residues 34-40) is exposed to the aqueous phase and lacks an ordered conformation. The secondary structure of segment B in micelles is consistent with the high-resolution electron cryomicroscopy model of bacteriorhodopsin (Henderson et al. (1990) J. Mol. Biol., 213, 899-929). PMID- 1511237 TI - A systematic comparison of three structure determination methods from NMR data: dependence upon quality and quantity of data. AB - We have systematically examined how the quality of NMR protein structures depends on (1) the number of NOE distance constraints, (2) their assumed precision, (3) the method of structure calculation and (4) the size of the protein. The test sets of distance constraints have been derived from the crystal structures of crambin (5 kDa) and staphylococcal nuclease (17 kDa). Three methods of structure calculation have been compared: Distance Geometry (DGEOM), Restrained Molecular Dynamics (XPLOR) and the Double Iterated Kalman Filter (DIKF). All three methods can reproduce the general features of the starting structure under all conditions tested. In many instances the apparent precision of the calculated structure (as measured by the RMS dispersion from the average) is greater than its accuracy (as measured by the RMS deviation of the average structure from the starting crystal structure). The global RMS deviations from the reference structures decrease exponentially as the number of constraints is increased, and after using about 30% of all potential constraints, the errors asymptotically approach a limiting value. Increasing the assumed precision of the constraints has the same qualitative effect as increasing the number of constraints. For comparable numbers of constraints/residue, the precision of the calculated structure is less for the larger than for the smaller protein, regardless of the method of calculation. The accuracy of the average structure calculated by Restrained Molecular Dynamics is greater than that of structures obtained by purely geometric methods (DGEOM and DIKF). PMID- 1511238 TI - Measurement of two-bond JCOH alpha coupling constants in proteins uniformly enriched with 13C. AB - A simple E.COSY type technique is described for measurement of two-bond JCOH alpha coupling constants in proteins that are uniformly enriched with 13C. The method has been used to measure 2JCOH alpha for 132 residues in the proteins calmodulin and staphylococcal nuclease having non-overlapping H alpha-C alpha correlations. Measured 2JCOH alpha coupling constants fall in the 0 to -9.5 Hz range. A separate experiment, measuring the accuracy of these values, indicates a root-mean-square error of 1 Hz. Comparison of the J couplings with the dihedral backbone angles from crystallographic studies confirms a weak but statistically significant correlation between the dihedral angle psi and the magnitude of 2JCOH alpha, but also indicates that parameters other than psi have a significant effect on the value of the coupling. PMID- 1511239 TI - Intracellular boron localization and uptake in cell cultures using imaging secondary ion mass spectrometry (ion microscopy) for neutron capture therapy for cancer. AB - Quantitative ion microscopy of freeze-fractured, freeze-dried cultured cells is a technique for single cell and subcellular elemental analysis. This review describes the technique and its usefulness in determining the uptake and subcellular distribution of the boron from boron neutron capture therapy drugs. PMID- 1511240 TI - The imaging and quantification of aluminium in the human brain using dynamic secondary ion mass spectrometry (SIMS). AB - Dynamic secondary ion mass spectrometry (SIMS) has been utilised to study the post-mortem distribution of aluminium in air-dried frozen sections from unfixed, unstained human brain in order to minimise contamination of the tissue and avoid redistribution and extraction of endogenous tissue aluminium. Substrates, sputter coated with silver, were found to be free of focal aluminum surface contamination and thus minimised substrate induced artefacts in the tissue aluminium ion image. SIMS imaging of aluminium secondary ions at a mass resolution that eliminated the major molecular interferences, combined with a photomontage technique provided a unique strategy for studying aluminium distribution in tissue unrivalled by other spatially resolved microanalytical techniques such as laser microprobe mass spectrometry or X-ray microanalysis. Using this strategy, high densities of focal aluminium accumulations have been demonstrated in the cerebral cortex of the majority of chronic renal dialysis patients studied. In contrast, such aluminium accumulations were absent in control patients. SIMS imaging of aluminium appeared to provide much better discrimination between the dialysis patient group and the control group than one of the most widely used techniques for measuring aluminium in bulk samples, graphite furnace atomic absorption spectrometry. Preliminary studies have shown the feasibility of quantifying focal aluminium SIMS images obtained from brain tissue using aluminium-loaded brain homogenates as reference standards. PMID- 1511241 TI - Preservation of the diffusible cations for secondary ion mass spectrometry. II. Artefacts in material embedded in araldite or melamine. AB - Flotation on hot water (about 60 degrees C) which is frequently employed to stretch semithin sections on substrates for SIMS (secondary ion mass spectrometry) microscopy, is the cause of numerous artefacts. In the case of epoxy resin-embedded tissue, one observes loss of potassium and sodium and accumulation of calcium. The relative contrast of cell nuclei in the ionic images, is rapidly affected by these ion migrations. After prolonged contact with hot water, tissue becomes uniformly emissive. In the case of hydrosoluble resin embedded tissue, potassium and sodium do not appear to be affected by the action of water, which suggests that they are covalently bound with chelating sites buried beneath the layer of water bound to the surface of the macromolecules. Calcium accumulates, probably on widely exposed anionic sites. Moreover, the domains observed in hydrosoluble resin-embedded tissue shrink differently according to the proportion of water removed by melamine; this can provide interesting information on the initial equilibrium between water, ion sand macromolecules. Our results seem to support the assumption that bound water should play an important role in the preservation of both macromolecular architecture and ion distributions. PMID- 1511243 TI - Biological SIMS microscopy literature. PMID- 1511242 TI - The role of secondary ion mass spectrometry (SIMS) in biological microanalysis: technique comparisons and prospects. AB - The virtues and limitations of SIMS ion microscopy are compared with other spectroscopic techniques applicable to biological microanalysis, with a special emphasis on techniques for elemental localization in biological tissue (electron, X-ray, laser, nuclear, ion microprobes). Principal advantages of SIMS include high detection sensitivity, high depth resolution, isotope specificity, and possibilities for three-dimensional imaging. Current limitations, especially in comparison to X-ray microanalysis, center on lateral spatial resolution and quantification. Recent SIMS instrumentation advances involving field emission liquid metal ion sources and laser post-ionization will help to minimize these limitations in the future. The molecular surface analysis capabilities of static SIMS, especially with the new developments in commercial time-of-flight spectrometers, are promising for application to biomimetic, biomaterials, and biological tissue or cell surfaces. However, the direct microchemical imaging of biomolecules in tissue samples using SIMS will be hindered by limited concentrations, small analytical volumes, and the inefficiencies of converting surface molecules to structurally significant gas phase ions. Indirect detection using elemental or isotopically tagged molecules, however, shows considerable promise for molecular imaging studies using SIMS ion microscopy. PMID- 1511244 TI - Preservation of the diffusible cations for SIMS microscopy. I. A problem related to the state of water in the cell. AB - The notion of diffusible ions is reviewed in the light of recent knowledge on the stage of water in biological matrices. It appears that ion distributions would be little affected as long as water-macromolecular equilibrium is maintained, but they risk to be significantly modified during dehydration, because the transformation of bound water into highly solvating free water can produce ion displacements. In addition, differently hydrated areas may undergo unequal volume variations. The principal modes of preparing material for SIMS (secondary ion mass spectrometry) microscopy are envisaged from this viewpoint. PMID- 1511245 TI - Sample preparation of animal tissues and cell cultures for secondary ion mass spectrometry (SIMS) microscopy. AB - Sample preparation is a critical step in the elemental analysis of animal tissues and cell cultures with ion microscopy. Since live cells cannot be analyzed with ion microscopy, a careful sample fixation is necessary which preserves the native structural and chemical integrity of a specimen. The evaluation of morphological and chemical integrity of a fixed specimen is necessary before any physiological explanation of ion fluxes is interpreted based on ion microscopy. For diffusible ion localization studies, strict cryogenic procedures are recommended. Examples are shown for diffusible ion microanalysis in frozen-freeze-dried tissues and cell cultures. Ion microscopy studies of tightly bound elements/molecules may be conducted in chemically fixed and/or plastic embedded specimens. Since it is not generally known which elements/molecules are tightly bound to the tissue matrix, a confirmation of elemental distribution with cryogenic procedures is desirable. A recent approach of combining laser scanning confocal fluorescence microscopy and ion microscopy on the same frozen freeze-dried cell is also discussed for recognizing smaller cytoplasmic structures in ion microscopy images. PMID- 1511246 TI - Scanning secondary ion analytical microscopy with parallel detection. AB - The secondary ion microscope described here allows to obtain the simultaneous registration of chemical and isotopic distribution maps of several elements composing the sample. The instrument has been specially designed to optimize both sensitivity and selectivity; bombardment with primary Cs+ ions to increase the ionization yields of negative secondary ions, efficient collection of secondary ions at the target surface, matching of the secondary ion beam etendue with the acceptance of the mass spectrometer working at high mass resolution, spectrometer with parallel detection capabilities. The probe diameter can be made as low as 30 nm and ion induced electron images registered at the same time as ion images. Presently, four ion micrographs are obtained simultaneously over a field of view up to 20 x 20 micro m2 containing up to 512 x 512 pixels. Examples are shown with an ion probe diameter of 0.1 microm. PMID- 1511247 TI - SIMS microscopy in the biomedical field. AB - We attempted to indicate the requirements for biomedical applications of SIMS microscopy. Sample preparation methodology should preserve both the structural and the chemical integrity of the tissue. Furthermore, it is often necessary to correlate ionic and light microscope images. This implies a common methodological approach to sample preparation for both microscopes. The use of low or high mass resolution depends on the elements studied and their concentrations. To improve the acquisition and processing of images, digital imaging systems have to be designed and require both ionic and optical image superimposition. However, the images do not accurately reflect element concentration; a relative quantitative approach is possible by measuring secondary ion beam intensity. Using an internal reference element (carbon) and standard curves the results are expressed in micrograms/mg of tissue. Despite their limited lateral resolution (0.5 microns) the actual SIMS microscopes are very suitable for the resolution of biomedical problems posed by action modes and drug localization in human pathology. SIMS microscopy should provide a new tool for metabolic radiotherapy by facilitating dose evaluation. The advent of high lateral resolution SIMS imaging (less than 0.1 microns) should open up new fields in biomedical investigation. PMID- 1511248 TI - Cytogenetic applications of high resolution secondary ion imaging microanalysis: detection and mapping of tracer isotopes in human chromosomes. AB - Analytical imaging by secondary ion mass spectrometry (SIMS) using a state-of-the art scanning ion microprobe enables the detection and mapping of tracer isotopes in human metaphase chromosomes. The stimulated mitosis of cells cultured in media containing labelled nucleosides, typically 14C-labelled thymidine or adenosine, and BrDU, yields chromosomes that have incorporated the labelled molecule in their constituent DNA. The label is subsequently detected and localized by SIMS imaging. The relative label signal intensities of sister chromatids can be quantified. The occurrence of sister chromatid exchanges (SCE) can be detected. The distribution of specific nucleosides can be directly mapped. This is non uniform along the chromatids, giving rise to characteristic banding patterns (SIMS bands) that seem to correspond to the well known G- or Q-bands resulting from conventional staining methods. The study of a number of cytogenetic problems is expected to benefit from the use of this new method of approach, similar in principle, but potentially more sensitive and capable of higher spatial resolution than autoradiography. PMID- 1511249 TI - Significance of SIMS microscopy for the radioiodine detection in animal and human thyroid tissue. AB - We defined the SIMS conditions for radioiodine detection in animal and man thyroid follicles, in tissue sections (3 microns) chemically fixed and resin embedded. Two radioisotopes were tested: 125I and 129I, of high (14 mCi 125I micrograms-1) and low specific activity (1.07 10(-6) mCi 129I micrograms-1). In animal study, Wistar rats fed a normal iodine diet (10 micrograms 127I day-1) were injected ip 24 h before sacrifice either with 125I (7 10(-3) micrograms) or with 129I at a dose identical to iodine diet (10 micrograms) or 3 times higher (30 micrograms). No SIMS signal of 125I was obtained in vivo due to its too low concentration, while radioiodine distribution was evidenced with both doses of 129I. Local concentration of previously stored 127I in follicular lumen was not modified, when compared to control (4.14 +/- 0.03 micrograms/mg, m +/- SE), by 125I or 129I at a dose of 10 micrograms, but was nearly doubled with 129I at a dose of 30 micrograms, proof of a pharmacological effect on thyroid iodine regulation. In human study 129I was excluded due to its long half-life (1.6 10(7) years), and 125I was tested only in vitro on two surgical specimens of normal perinodular thyroid tissue maintained in mini-organ culture for 48 h in presence of 100 microCi/ml of 125I. The 125I was detectable, its concentration was 1,000 fold higher than that of 127I (1.5 +/- 0.004 micrograms/mg). For both in vivo and in vitro studies, a positive correlation exists between newly organified radioiodine (125I or 129I) and previously stored iodine (127I).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1511250 TI - Mapping the cellular distribution of labelled molecules by SIMS microscopy. AB - We took advantage of one of the main possibilities of ion microscopy, ie isotopic analysis, to study the cellular distribution of molecules labelled either with carbon 14 or with stable isotopes of low natural abundance such as nitrogen 15 and deuterium. The surface of the sample is bombarded with an ion beam (O2+, Cs+ etc). Secondary ions emitted from the sample are filtered by a mass spectrometer and the distribution of the labelling isotope is recorded. In this way, we obtained images showing the characteristic distribution of 14C-thymidine and D arginine in human fibroblasts, and of 15N-adenine in organotypic cultures of human breast cancer cells. The spatial resolution on the acquired images was close to 0.1 micron when using the UPS-ONERA ion microprobe. The sensitivity of the method for detecting carbon 14 is far greater than that of autoradiography and the technique is both fast and quantitative. On the other hand, the capacity of ion microscopy for studying the tissular distribution of molecules labelled with stable isotopes, opens the way for biological and pharmacological tracer studies of human diseases. PMID- 1511251 TI - SIMS microscopy: a tool to measure the intracellular concentration of carbon 14 labelled molecules. AB - Monolayer cultures of human fibroblasts were incubated for 24 h with 14C-arginine and observed by means of SIMS microscopy (ion microscopy). Carbon 14 imaging showed the intracellular distribution of labelled arginine which featured high nuclear incorporation. The local concentration of this amino acid in different cells and intracellular structures was assessed through local isotopic 14C/12C ratio measurement. This relates the signal intensity of the labelling isotope carbon 14 to that of the corresponding natural isotope (carbon 12) of known tissular concentration. Using this method we were able to measure minor variations in the molecular concentration of arginine (expressed as mumol/g of tissue) between different fibroblasts. Results of this study indicate that SIMS microscopy is well adapted to carbon 14 detection and can provide quantitative maps of the cellular and subcellular distribution of 14C-labelled molecules. PMID- 1511252 TI - Mapping of intracellular halogenous molecules by low and high resolution SIMS microscopy. AB - The subcellular distribution of halogenous molecules has been studied by SIMS microscopy in cultured cells of a human breast carcinoma (MCF-7 cell line). Two instruments of microanalysis were used. A low lateral resolution ion microscope (SMI 300 CAMECA) and a prototype scanning ion microscope equipped with a cesium gun that gives high lateral resolution images. This apparatus has been developed by G Slodzian, in Onera Laboratories (Office National d'Etudes et de Recherches Aerospatiales). Molecules studied by low lateral resolution ion microscope were halogenous steroids: fluorometholone, triamcinolone, bromocriptine and bromoandrosterone. Analytical images show that the first two compounds are mainly localized in the nuclear structure of MCF-7 cells whereas the last two molecules are localized in cytoplasm of these cells. Images were obtained with a resolution of 1 micron. With the scanning ion microscope, it is now possible to obtain images at the ultrastructural level. Four analytical images can be simultaneously obtained by a single scan of the imaged area, corresponding to a depth of erosion of the section of ten nm. The intranuclear distributions of three pyrimidine analogs, 5-bromo-2'-deoxyuridine, 5-iodo-2'-deoxyuridine and 5-fluorouracil have been studied in phase S and M of MCF-7 cells and these images have been compared to the distribution of sulfur, nitrogen and phosphorus. All these images have been obtained with a lateral resolution better than 100 nm. PMID- 1511253 TI - Subcellular localization of two neurotropic drugs in three varieties of central nervous system cells by secondary ion mass spectroscopy (SIMS) microscopy. AB - The intracellular localization of two neurotropic drugs, flunitrazepam (benzodiazepine) and triflupromazine (phenothiazine), was studied by secondary ion mass spectrometry microscopy (SIMS) in three varieties of cells. The images of the intracellular distributions of the two drugs are easily obtained by selecting the fluorine atom of the molecules. These images show that the drug from the benzodiazepine group is mainly located in the nuclei, whereas the phenothiazine is exclusively located inside the cytoplasm. PMID- 1511254 TI - Marrow transplantation for Fanconi anemia with or without leukemic transformation: an update of the Seattle experience. AB - Between March 1973 and August 1990, 17 patients with Fanconi anemia (FA) underwent bone marrow transplantation in Seattle. Marrow donors were HLA identical siblings (n = 14), phenotypically HLA identical parents (n = 2) and a one antigen mismatched parent (n = 1). Patients with no evidence of leukemic transformation (n = 12) were conditioned with 140-200 mg/kg cyclophosphamide (CY). Of five patients with leukemic transformation, four received CY (120 mg/kg) plus 12 Gy fractionated total body irradiation and one patient received busulfan (14 mg/kg) and CY (100 mg/kg). All patients engrafted; however, one patient whose sibling donor's cells showed variable results when assayed for chromosome instability required two additional marrow infusions. Toxicity associated with the conditioning regimen included severe oral mucositis (n = 14), hemorrhagic cystitis (n = 11) and diffuse erythroderma (n = 3). Seven of the 12 patients without leukemic transformation are surviving 1-17 years (median = 5 years) after transplant, with an estimated survival probability at 5 years of 65% (95% CI 0.31; 0.85). Two patients developed squamous cell carcinoma of the tongue greater than 10 years post-transplant. One of these patients died at 10.3 years as a result of the malignant process, and the other is disease free more than 12 years post-transplant. Of the five patients with leukemic transformation, one is alive at 8 years. These data demonstrate that marrow transplantation can offer long term survival for patients with FA, engraftment can be achieved with reduced doses of CY in FA patients, and less toxic preparative regimens are needed for FA patients who have developed leukemic transformation. PMID- 1511255 TI - Cytokine activity after allogeneic bone marrow transplantation. IV. Production of mRNA for IL-3 and GM-CSF by mitogen-stimulated circulating mononuclear cells. AB - The ability of circulating mononuclear cells from recipients of HLA identical sibling marrow transplants to generate messenger (m) RNA for the haemopoietic growth factors interleukin-3 (IL-3) and granulocyte-macrophage colony-stimulating factor (GM-CSF) upon mitogen stimulation was investigated. The amount of IL-3 mRNA per ml of blood and IL-3 mRNA per 10(7) mononuclear cells as well as the amount of GM-CSF mRNA per ml of blood was significantly lower in transplant recipients than in normal volunteers. Lower values for mRNA expression for both IL-3 and GM-CSF were associated with the use of immunosuppressive therapy post transplant. No correlation was found between the expression of message for either cytokine, or the presence or absence of acute graft-versus-host disease at the time of testing. While there was no correlation between the quantity of GM-CSF message produced and time elapsed post transplant, IL-3 message expression increased slightly with increasing time post transplant. These defects of haemopoietic regulators constitute another parameter of impaired cellular immunity occurring after allogeneic marrow transplantation. PMID- 1511256 TI - Sexual satisfaction in survivors of bone marrow transplantation. AB - Of 157 (80%) adult survivors of bone marrow transplantation, 126 responded to a mailed survey 6-149 months after transplant concerning their ability to attain sexual satisfaction. Sixty-five percent of the subjects indicated some degree of sexual satisfaction (with 29% indicating a high degree of satisfaction). Thirteen percent were neutral and 22% were dissatisfied. Gonadal physiological disturbances were present in most subjects as a result of intensive treatments. Fifty-seven percent of women were receiving estrogen replacement, and only 40% had regular menses. Twenty-four percent of men had difficulty with erections and 13% had ejaculatory dysfunction. For men, difficulties with erection (r = 0.54, p less than 0.001) or ejaculation (r = 0.52, p less than 0.001) were associated with inability to attain sexual satisfaction. For women, loss of menses (r = 0.34, p = 0.008) was associated with inability to attain sexual satisfaction. Although few women had abnormally low serum estradiol (even with hormonal supplementation), and none of the 43 men tested had abnormally low serum testosterone, sexual satisfaction correlated with serum levels of estrogen in women (r = 0.42, p = 0.04) and serum testosterone in men (r = 0.28, p = 0.04). Forty-two subjects rated their level of sexual satisfaction before and after transplant. Post-transplant satisfaction was not associated with pretransplant satisfaction (r = 0.07, p = 0.67).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1511257 TI - Relapse of leukemia after bone marrow transplantation: effect of second myeloablative therapy. AB - Twenty-three patients with recurrent leukemia after bone marrow transplantation (BMT) underwent a second myeloablative therapy followed by second transplant between June 1977 and April 1991. Patients had either acute lymphocytic leukemia (n = 4), acute myelogenous leukemia (n = 7) or chronic myelogenous leukemia (n = 12). The median age was 29 years and the median interval between first and second BMT was 22.6 months. The second preparative therapy consisted of cyclophosphamide (200 mg/kg) and total body irradiation (1200 cGy) in nine patients and busulfan (16 mg/kg) and cyclophosphamide (120-200 mg/kg) with or without etoposide (30-60 mg/kg) in 14 patients. The same sibling donor (three syngeneic, 20 allogeneic) was used for both transplants. All patients demonstrated prompt neutrophil recovery (median 21 days) with donor-derived hematopoiesis documented in 16 of 16 evaluable patients. With a median follow-up of 24 months after second BMT, the survival, event-free survival and probability of remaining in remission at 26 months are 47%, 38% and 76% respectively. Outcome was best in patients with chronic myelogenous leukemia (7/12 survivors) and worst in patients with acute leukemia (2/11 survivors). Thus, the data would suggest that (1) selected patients with recurrent leukemia after BMT can still be cured with myeloablative therapy and second BMT, and (2) further improvements in outcome will be dependent upon the reduction of regimen-related toxicity. PMID- 1511258 TI - Propranolol for the treatment of cyclosporine-induced headaches. AB - We studied whether small doses of propranolol given orally have an effect on headaches that are associated with intravenous cyclosporine therapy. In seven patients who had severe cephalalgia associated with intravenous cyclosporine post bone marrow transplant, oral propranolol promptly relieved the symptoms in four patients. Intravenous propranolol was not effective in one patient who was unable to take oral medications. Propranolol should be considered as an alternative to chronic narcotics in patients with headaches due to cyclosporine. PMID- 1511259 TI - Abdominal presentation of varicella zoster infection after bone marrow transplantation. PMID- 1511260 TI - Bone marrow transplantation activity in Europe 1990. PMID- 1511261 TI - Escalating doses of etoposide with dimethylbusulfan as conditioning for autologous bone marrow transplantation. PMID- 1511262 TI - The effects of body size on functional properties of middle ear systems of anuran amphibians. AB - Both tympanic and nontympanic pathways of sound reception are utilized by anuran amphibians. The relationship between body size and the acoustic responsiveness of various body surfaces that may serve as pathways for sound reception in anurans was analyzed. The motion of the different surfaces (tympanum, lateral body wall, lateral head surface, and dorsal shoulder surface) produced by sound was measured with a laser vibrometer in anuran species. The frequency response and amplitude levels of motion of these body surfaces clearly were linked with size. In all animals, nontympanic surfaces were most responsive to low frequencies, and the tympanum was most responsive to high frequencies. However, the responsiveness of nontympanic surfaces was greater, and extended to higher frequencies, in small anurans. In the smallest animals studied, nontympanic surfaces were often more responsive than the tympanum up to frequencies as high as 2500 Hz. In larger anurans, nontympanic responsiveness tended to decrease, and tympanic responsiveness tended to increase. In the largest animals studied, the tympanum was the most responsive surface at all except very low frequencies below about 200-300 Hz. These results suggest that small anurans can utilize nontympanic pathways for effective sound reception over a broad frequency range, whereas large anurans are more restricted to using a standard tympanic middle ear for hearing. This effect of body size on the utility of nontympanic sound reception may explain evolutionary patterns of tympanic ear reduction and loss observed in several small species of anurans. PMID- 1511263 TI - Auditory cortex of the long-eared hedgehog (Hemiechinus auritus): II. Tuning properties. AB - The forebrain of hedgehogs is considered by many investigators as one of the simplest and most primitive among extant placental mammals. In a recent study we have shown that the auditory cortex of the long-eared hedgehog (Hemiechinus auritus) comprises two distinct auditory fields, which are tonotopically organized. In this study, we describe tuning properties of single cells in these two fields. Application of the Q10dB and Square Root measures for determining sharpness of tuning revealed that, although most of the cells in the more anterior field, which is considered primary, are sharply tuned, on the average they are more broadly tuned than cells in the primary auditory cortex of other mammals. In the posterior field, the distribution of narrowly and broadly tuned cells is equal. Narrowly tuned cells in both fields are equally narrow, as are the broadly tuned cells. Latencies of single cells in both fields are frequency and intensity dependent and are somewhat longer than these found in other mammals. The distribution of BFs vs. threshold intensity matches fairly well the behavioral audiogram previously described. Our findings suggest that, in spite of the view that the isocortex of hedgehogs represents a 'primitive' condition, some basic tuning properties of their auditory cortex cells are comparable to those of other mammals. PMID- 1511264 TI - The visual forebrain and eating in pigeons (Columba livia). AB - The contribution of forebrain structures to the control of visually guided eating behaviors was studied using a technique for reversible 'visual decerebration'. The procedure is based upon the fact that structures in the thalamus and telencephalon receive their visual inputs primarily from the contralateral eye. When the eye contralateral to the ablated hemisphere is occluded, the remaining eye has unilateral access to these structures. When the eye ipsilateral to the ablated hemisphere is occluded, the bird is functionally decerebrate; i.e., visual processing by the remaining eye is restricted to structures caudal to the forebrain. The performance of normal and hemispherectomized subjects under binocular and monocular (unilateral, decerebrate) viewing conditions was compared on tests of ingestive efficiency, identification, conditioned peck localization, and grasping. In normal subjects, differences between right and left eye were not significant on any of these tasks. In hemispherectomized subjects, monocular performance on the first three tasks depended critically upon which eye was occluded. In the decerebrate condition (i.e., when the eye opposite the ablated hemisphere was used) performance on the identification, ingestive efficiency and peck localization tasks was significantly degraded, but grasping was unimpaired. We conclude that the brain structures critical for the visuomotor control of grasping lie caudal to the forebrain. PMID- 1511265 TI - Retinal projections in the bowfin, Amia calva: cytoarchitectonic and experimental analysis. AB - The retinofugal projections in the bowfin, a non-teleost actinopterygian, were studied by autoradiographic and horseradish peroxidase methods, and the cytoarchitecture of retinorecipient regions of the diencephalon was analyzed with serially sectioned, Bodian stained material. Nuclei were identified in the thalamus, the periventricular portion of the posterior tuberculum, synencephalon, and pretectum which are homologous to like-named nuclei in teleosts and other non teleost actinopterygian fishes. Of particular note, a posterior pretectal nucleus and, possibly, a homologue of nucleus corticalis were found to be present in the pretectum. These nuclei have previously been identified only in teleosts. The posterior pretectal nucleus is relatively small in the bowfin, and the distribution of a small, versus a large, posterior pretectal nucleus in Teleostei and Halecomorphi suggests that this nucleus was small plesiomorphically. The pattern of retinofugal projections in the bowfin is similar to that in other non teleost actinopterygian fishes and in teleosts in most regards. Contralaterally, the retina projects to nuclei in the dorsal and ventral thalamus, superficial and central pretectum, dorsal and ventral accessory optic nuclei, and to the optic tectum. Additionally, there are sparse projections to the suprachiasmatic nucleus in the preoptic area, the periventricular nucleus of the posterior tuberculum, and the dorsal and ventral periventricular pretectal nuclei. Ipsilateral projections are sparse and are derived from fibers which do not decussate in the optic chiasm. Undecussated ipsilateral retinal projections, as present in the bowfin, are a widely distributed character in vertebrates and appear to be plesiomorphic for vertebrates. PMID- 1511266 TI - Ketanserin reduces neuronal calcium accumulation and cell death in the hippocampus of the Mongolian gerbil after transient forebrain ischemia. AB - Excessive neuronal activity combined with an increased release of neurotransmitters is supposed to contribute to the delayed neuronal degeneration in animal models of transient cerebral ischemia. Since evidence is accumulating that serotonin (5-HT) exerts an excitatory effect on neurons via 5-HT2 receptors we tested the hypothesis that 5-HT2 receptor antagonists could protect neurons in the gerbil after transient bilateral carotid occlusion. In a first series of experiments, the 5-HT2 receptor antagonist ketanserin was injected intraperitoneally 15 min prior to 5 min of forebrain ischemia and given twice daily on the following 3 days. At a dose of 10 mg/kg i.p., the number of intact hippocampal CA1 neurons was significantly higher than in the saline-treated group and reached 74% of the sham-operated controls. In addition, the degree of neuronal damage correlated with an increased intracellular Ca2+ content in CA1 pyramidal neurons as revealed by arsenazo(III) staining with a procedure modified for paraffin sections. In a second series of experiments, ketanserin (10 mg/kg) was injected at various times after onset of ischemia. Up to a period of 90 min after ischemia, the number of intact CA1 pyramidal cells in ketanserin-treated animals was still significantly higher than in the saline-treated group. These results indicate that 5-HT2 receptor antagonists may protect neurons against ischemic damage even when the treatment is started after onset of ischemia. It remains to be investigated whether the neuroprotective effect of ketanserin is due to a neuronal action or to an inhibition of cerebrovascular vasospasm. PMID- 1511267 TI - A novel hypothalamic-dispersed pituitary co-perifusion model for the study of growth hormone secretion. AB - This study presents a novel, in vitro, hypothalamic-dispersed pituitary co perifusion system (HPPS) developed to examine the influence of the hypothalamus on pituitary growth hormone (GH) secretion in a controlled environment. In this perifusion system, dispersed rat pituitary cells were loaded onto Biogel P-2 (P 2) beads in a 0.5-ml plexiglas chamber and were submerged in a 37 degrees C water bath. After stabilization, two hypothalami were placed into each chamber on a thin layer of P-2 beads and the chamber was re-equilibrated. To test the system, pituitary cells were stimulated either directly with growth hormone-releasing factor (GRF) or indirectly via the hypothalamus, with clonidine, an alpha 2 adrenergic (alpha 2) receptor agonist. Perifusion of HPPS or pituitary cells with GRF (40 ng/ml) induced a substantial endogenous GH surge. Clonidine (2 x 10(-8) M) treatment stimulated a GH surge in HPPS chambers, but not in chambers containing only pituitary cells. Thus, somatotrophs respond to hypothalamic factors released in response to clonidine and not directly to alpha 2 stimulation. To determine if the components involved in GH feedback are present in the perifusion system, HPPS chambers were sequentially perifused with hGH, clonidine, and GRF. hGH pretreatment suppressed the clonidine but not the GRF induced GH surge(s) observed in chambers perifused with clonidine and GRF only. In chambers only containing pituitary cells, GH was only increased in response to GRF when sequentially perifused with all three substances. This study demonstrates the dynamic interaction between the hypothalamus and pituitary in the regulation of GH secretion in vitro.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1511268 TI - Assessment of dopamine and its metabolites in the intracellular and extracellular compartments of the rat striatum after peripheral administration of L-[11C]dopa. AB - Success in the synthesis of L-3,4-[beta-11C]dihydroxyphenylalanine (L-[11C]DOPA) and its application to positron emission tomography encouraged us to perform radioactive metabolite analyses in rats in an early phase after peripheral injection of L-[11C]DOPA. Following intravenous injection of [11C]DOPA, the radioactivity associated with DOPA and its metabolites was determined in the striatum after decapitation and in striatal extracellular fluid using in vivo brain microdialysis. Without pretreatment, 70-80% of 11C-radioactivity taken up into the striatum was associated with acidic metabolites of dopamine (DA) from 2 to 30 min after administration of L-[11C]DOPA with or without 300 micrograms/kg of unlabelled L-DOPA. In contrast, 80-90% of 11C-radioactivity in the striatum was associated with DOPA and DA after pretreatment with benserazide (25 mg/kg, i.p.) followed by administration of L-[11C]DOPA with or without unlabelled L DOPA. The radioactivity in the DOPA fraction decreased with time (from 35% of 11C radioactivity in the striatum at 5 min to 10% at 30 min), but that in the DA fraction increased (from 57% to 68%). The 11C-radioactivity in the extracellular fluid determined by brain microdialysis was less than 0.4% of that in the whole striatum and no radioactivity was present in the DA fraction. These results suggest that, in an early phase after administration of L-[11C]DOPA, [11C]DA is the main metabolite and is localized exclusively in the intracellular compartment within this time frame. PMID- 1511269 TI - Sex differences in estrogen receptor binding in the rat hypothalamus: effects of subsaturating pulses of estradiol. AB - The effects of subsaturating pulses of estradiol on cell nuclear retention of estrogen receptors in brain regions of male and female rats were determined. In the first experiment, age-matched adrenalectomized/gonadectomized (ADX/GDX) rats were killed 1 h after i.v. injection of a subsaturating dose of free estradiol (1.0 microgram/kg b. wt.) and cell nuclear estrogen receptor binding was measured in microdissected brain areas by an in vitro exchange assay. As we have previously reported with saturating doses of estradiol (3.6-36.0 micrograms/kg b. wt.), a greater concentration of receptors was measured in the ventromedial nucleus (VMN), periventricular preoptic area (PVPOA), and medial preoptic area (mPOA) of the female than in the same regions of the male brain. Binding levels did not differ between the sexes in the bed nucleus of the stria terminalis, arcuate nucleus, or the corticomedial amygdala. In the second experiment, GDX/ADX male and female rats received either a single or double pulse of 0.5 microgram estradiol/kg b. wt. administered 6 h apart. Rats were killed 1 h after the second pulse. In animals treated with a single pulse of estradiol 1 h before sacrifice, higher concentrations of estrogen binding were measured in the female VMN and PVPOA than in the male. Except in the mPOA, the concentration of estrogen receptor binding measured was not different from that measured in animals that had received an additional, earlier pulse of estradiol. In this area, receptor concentrations were lower in male rats treated with two pulses than in males treated with one pulse.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1511270 TI - Carbachol-induced rhythmic slow activity (theta) in cat hippocampal formation slices. AB - Application of the cholinergic agonist, carbachol, produced theta-like rhythmical waveforms, recorded in the stratum moleculare of the dentate gyrus in the cat hippocampal formation slices. This effect of carbachol was antagonized by atropine but not D-tubocurarine. These results provide first direct evidence that the hippocampal formation neuronal network in the cat is capable of producing synchronized slow wave activity when isolated from pulsed rhythmic inputs of the medial septum. PMID- 1511271 TI - Induction of c-fos mRNA in rat brain by conditioned and unconditioned stressors. AB - Intense depolarizing stimuli induce the expression of the proto-oncogene c-fos which may be useful as a marker of neuronal activity. To determine if mild physical and behavioral stressors may also induce c-fos expression, we subjected rats to an unconditioned stressor (footshock) or a conditioned stressor (a tone previously paired with footshock) and measured c-fos mRNA levels in various brain regions using in situ hybridization. Removing rats from their home cage and exposing them to a tone was sufficient to cause increases in c-fos mRNA in several forebrain areas while further increases in c-fos occurred in the septum, cingulate cortex, and endopiriform nucleus in response to acute footshock stress. Both unconditioned and conditioned stressors increased c-fos mRNA levels in the locus ceruleus which correlated with stress-induced plasma corticosterone concentrations. Unconditioned footshock stress also increased c-fos mRNA in the hypothalamic paraventricular nucleus (PVN). However, neither conditioned nor unconditioned stressors induced c-fos in the PVN in rats which had been previously exposed to footshock. C-fos appears to be a sensitive marker for stress-responsive brain areas and may be important in mediating long-term neurochemical changes that result from stress. PMID- 1511272 TI - The central effect of methionine-enkephalin on NK cell activity. AB - The central effect of opioid peptide on natural killer (NK) cell activity in BALB/c mice was investigated. Injection of methionine-enkephalin (Met-Enk), 0.02 microgram/mouse or 1 microgram/kg, directly into the cisterna magna (CM) of the brain, resulted in a significant enhancement of NK cell activity. This enhancement was blocked by opiate antagonists, naltrexone and quaternary naltrexone. The same dose of Met-Enk had no effect on NK cell activity when given to the mouse intraperitoneally or intravenously. Moreover, des-tyrosine methionine-enkephalin injected into the CM at 1 microgram/kg, had no effect on NK cell activity. The results indicate that activation of an opioid-mediated pathway in the central nervous system is capable of activating the pathways that stimulate the NK cell response in the periphery. PMID- 1511273 TI - Fast cyclic voltammetry of oxidizable species; depth profile in the rat striatum with and without potassium stimulation of the median forebrain bundle. AB - Fast cyclic voltammetry was used to monitor the release of dopamine in the caudate nucleus following potassium stimulation of the median forebrain bundle and to determine the characteristics of the small basal oxidation current while dipping of an electrode with a large tip (0.3 mm) in the caudate nucleus. The oxidation current was shown to be greater just after the electrode reached the caudate area than at a time 15-20 s after its arrival. There was less current increase observed when the tip reached the cortex and no current was observed in the white matter or with the electrode returning or with repeated passage along the same track. Potassium stimulation of median forebrain bundle induced an initial low magnitude dopamine release which disappeared within minutes. The basal oxidation current increased step by step after a few potassium stimulations. This effect was not blocked by pargyline (75 mg/kg) whereas L-DOPA (200 mg/kg) was shown to increase it. It is thought that the large tip of the lowered electrode can destroy neurons and induce the release of intracellularly stored compounds into the extracellular space. We consider also dopamine to be responsible for the increase in oxidizable current just after the electrode movement stopped. PMID- 1511274 TI - Behavior of inhibitory and excitatory propriobulbar respiratory neurons during fictive vomiting. AB - The behavior of propriobulbar respiratory neurons was studied during fictive vomiting in decerebrate, paralyzed, artificially ventilated cats. Fictive vomiting was identified by a characteristic series of synchronous phrenic and abdominal nerve bursts, induced by electrical stimulation of abdominal vagal afferents and/or i.v. infusion of emetic drugs. Data were obtained from inspiratory neurons having decrementing (I-DEC) or constant (I-CON) discharge patterns and expiratory decrementing (E-DEC) neurons located in the Botzinger complex and adjacent rostral ventral respiratory group. These neurons are known to make excitatory (I-CON) and inhibitory (I-DEC, E-DEC) connections with a variety of medullary respiratory neurons. During fictive vomiting: 8 of 14 I-DEC neurons fired in phase with synchronous bursts of phrenic and abdominal nerve discharge; the other 6 were silent. Of 12 I-CON neurons, 5 fired in phase with phrenic and abdominal bursts; 7 were silent. All (6) E-DEC neurons were either silent or fired weakly between bursts of phrenic and abdominal discharges. The possible roles of I-DEC and I-CON neurons in actively reorganizing the behavior of other respiratory neurons during fictive vomiting are discussed. In particular, the firing of many I-DEC neurons was found to be appropriate to inhibit inspiratory, and two types of expiratory, bulbospinal neurons during fictive vomiting. PMID- 1511275 TI - Fos-like immunoreactivity in the rat superficial dorsal horn induced by formalin injection in the forepaw: effects of dorsal rhizotomies. AB - As previously described at the lumbar spinal level, we found that 2 h after subcutaneous formalin injection in the distal part of the fore-limb, Fos-like immunoreactivity (FLI) was induced in the ipsilateral cervical enlargement. Not surprisingly, as the injection site corresponds to the distal part of the C6-C8 dorsal root dermatomes, maximal labelling which predominated in the superficial laminae, was observed in the C6-C8 segments and to a lesser extent in C5. Similar experiments were performed on rats which underwent various types of unilateral dorsal rhizotomies (DRh) 7 days before formalin injection. In animals with C4, C5, T1 and T2 DRh sparing C6-C8 the rostrocaudal distribution was similar to the intact one. But, in animals having C4-T2 DRh sparing one single root, C7, the segmental FLI distribution was modified: it was slightly increased in C7, decreased in C6 and significantly decreased in C8. As expected, no FLI was found in animals with C4 to T2 DRh. The spared root model provides information about the segmental distribution in the cervical spinal cord of the input brought by a single root following stimulation of the distal forelimb, i.e., maximal distribution in the entry segment, but also in the two rostral and one caudal segments. PMID- 1511276 TI - The neurotoxic effects of p-chloroamphetamine in rat brain are blocked by prior depletion of serotonin. AB - Systemic administration of p-chloroamphetamine (PCA) causes degeneration of serotonergic (5-HT) axons, but recent data indicate that this drug itself is not neurotoxic when applied directly to 5-HT axons. The present study was designed to test whether the toxic effects of PCA in the brain are dependent on release of endogenous 5-HT and to identify which stores of 5-HT are involved. The long-term effects of PCA on brain levels of 5-HT and on central 5-HT axons were determined in rats that had been initially depleted of 5-HT by administration of p chlorophenylalanine and reserpine. The results show that transient depletion of 5 HT provides substantial protection against subsequent PCA-induced degeneration of 5-HT axon terminals; the neurotoxicity induced by PCA thus appears to be dependent on the presence of endogenous stores of 5-HT. In addition, the protective effect of 5-HT depletion is found only after pretreatment regimens that deplete peripheral as well as central stores of 5-HT. We interpret this finding as evidence that release of 5-HT from peripheral storage sites may be necessary for the expression of PCA-induced toxicity. Based on these results, we propose that central neurotoxicity is not induced by a direct action of PCA alone but may require or be augmented by a toxic metabolite of 5-HT. PMID- 1511277 TI - Bradykinin modulation of a spinal nociceptive reflex in the rat. AB - Bradykinin (BK) is a potent algesic compound. Therefore, we hypothesized that BK, acting as a peripheral noxious stimulus, would attenuate or inhibit responses to another noxious stimulus. When administered intravenously (i.v.) to rats lightly anesthesized with pentobarbital, BK produced a dose-dependent (12-144 micrograms/kg) inhibition of the nociceptive tail-flick (TF) reflex. BK also produced a dose-dependent decrease in mean arterial blood pressure, a subsequent increase in heart rate and an increase in the rate of respiration. The latency to the maximal effect of BK on the TF reflex was 10 s and was occasionally preceded by pseudoaffective responses at doses greater than 48 micrograms/kg BK. Neonatal treatment with capsaicin (50 mg/kg, subcutaneous) significantly attenuated BK produced inhibition of the TF reflex indicating that BK was acting via peripheral afferents to inhibit the TF reflex. Reversible cold block or complete spinal transection at a low thoracic level (T9-12), but not reversible cold block at a high cervical level (C1-2), significantly attenuated BK-produced inhibition of the TF reflex, suggesting that BK activates afferents which enter the spinal cord between C2 and T9. Pretreatment with intrathecally administered phentolamine (30 micrograms), an alpha-adrenoceptor antagonist, or methysergide (30 micrograms), a non-selective serotonin receptor antagonist, did not alter BK-produced inhibition of the TF reflex, further supporting the absence of activation of descending systems from the brainstem by i.v. BK. While coadministration of PGE2 and BK significantly potentiated BK-produced inhibition of the TF reflex, neither bilateral removal of the stellate ganglion nor bilateral cervical vagotomy significantly affected the inhibitory action of i.v. BK on the TF reflex. These results suggest that i.v. BK inhibits the nociceptive TF reflex by activation of capsaicin-sensitive visceral afferents entering the spinal cord between C2 and T9. PMID- 1511278 TI - Behavioral modulation of sensory responses of primate putamen neurons. AB - Sensory response properties of putamen neurons were investigated in 4 awake macaque monkeys while the animals performed GO/NO-GO tasks guided by sensory stimuli. In the GO condition, visual stimuli served as a trigger for a sequence of repetitive elbow flexion-extensions and auditory stimuli served as a trigger for orofacial movements, while the identical sensory stimuli required the animals to withhold movements in the NO-GO condition. Short latency responses to visual and/or auditory stimuli were observed in 206 type I cells with tonic discharges at about 2-7 Hz, with a characteristic discharge rhythm and in 57 type II cells with low spontaneous discharge rates, usually less than 0.5 Hz, which showed burst discharges during the tasks. Most of these cells (163/206 type I cells, 52/57 type II cells) responded differentially to identical sensory stimuli presented in the GO and NO-GO conditions. The responses to sensory stimuli presented in the GO condition were much larger in 67% of type I cells and 58% of type II cells than the responses to identical stimuli presented in the NO-GO condition. On the other hand, 12% of type I and 33% of type II cells showed larger responses in the NO-GO than in the GO condition. It is suggested that the strong behavioral modulation of striatal sensory responses serves as a mechanism to start the neural processes for preparation and/or initiation or withholding of particular movements associated with learned sensory stimuli. PMID- 1511279 TI - Distribution of [3H]clonidine binding sites in the brain of the convulsive mutant quaking mouse: a radioautographic analysis. AB - The radioautographic analysis of [3H]clonidine binding was performed on brain slices from the convulsive mutant mice quaking and their controls of the same strain. In the quaking mice significant increases were observed mostly in the brainstem and the cerebellum, but also in a few regions of the forebrain, such as the lateral and medial thalamic nuclei, the medial geniculate nucleus, the amygdala and the hypothalamus. Other regions, such as the cerebral cortex and the hippocampus, which are classically involved in various models of epilepsy, but not in the quaking mice, did not show any modification of [3H]clonidine binding. A high degree of correlation was found between the structures with an increased density of alpha 2-adrenoceptor binding sites and the distribution of regions from which seizures can be elicited by intracerebral electrical stimulation in head-restrained quaking mice. This comparison emphasizes the role of noradrenaline acting at the level of alpha 2-adrenoceptors in the epileptic syndrome of the quaking mutants. PMID- 1511280 TI - Carnosine-like immunoreactivity is associated with synaptic vesicles in photoreceptors of the frog retina. AB - The distribution of carnosine-like immunoreactivity in photoreceptors of the frog retina was studied by post-embedding electron microscope immunocytochemistry. Different fixation and embedding procedures were applied and the best results were achieved on sections from tissue embedded in the hydrophilic resin LR White. All photoreceptor types present in the frog retina (red and green rods, single and double cones) were intensely reactive for the carnosine antiserum. The immunoreactivity was particularly prominent in the synaptic terminal, nucleus and myoid, but decreased in the ellipsoid and in the outer segment. Muller glial cells and horizontal and bipolar cell processes in the outer plexiform layer were completely unstained. At the level of the photoreceptor terminals, the presence of gold particles within the synaptic vesicles could be demonstrated. This study is the first to provide the anatomical evidence for the presence of carnosine in the synaptic vesicles of a nervous cell. The present data may be relevant to the understanding of the biological functions of carnosine (and related dipeptides) and offer an exploitable system in which to verify its proposed role as a neurotransmitter or neuromodulator in sensory systems. PMID- 1511282 TI - Properties of favored patterns in spontaneous spike trains and responses of favored patterns to electroacupuncture in evoked trains. AB - By using 'the modified detection method', our previous study has shown that all spontaneous spike trains recorded from several areas of brain and spinal cord have favored patterns (FPs). The present study further shows that: (1) all newly detected spike trains from substantia nigra zona compacta, nucleus periventricularis hypothalami and nucleus hypothalamicus posterior also have FPs, and some spike trains from neurons in the same nucleus have a common favored pattern (CF, i.e. they share the same FP), indicating that FP and CF in spike trains are common phenomena; (2) all serial correlation coefficients of FP repetitions (in serial order) in different spike trains detected are less than 0.3 (close to 0), revealing that the repetition of FPs is a renewal process; (3) in different periods of the spike trains evoked by electroacupuncture (EA), the number of different FPs and the number of repetitions of the same representative FP either increase or decrease along with the change of firing rate. The tendencies of these changes are very similar, but after EA the repetitions of different FPs in the same spike trains change differently, showing that different (hidden) responses exist at the same time. The above results suggest that the FPs in spike trains may represent various neural codes, and 'the modified detection method of FP' can pick up more information from spike trains than the firing rate analysis, hence it is a very useful tool for the study of neural coding. PMID- 1511281 TI - Semi-quantitative analysis of the effects of estrogen on CGRP- and methionine enkephalin-immunoreactivity in the periventricular preoptic nucleus and the medial preoptic area of female rats. AB - The effects of 17 beta-estradiol (E2) on calcitonin gene-related peptide (CGRP)- and methionine-enkephalin (Met-Enk)-immunoreactive (IR) nerve fibers in the periventricular preoptic nucleus (Pe) and the medial preoptic area, including the medial preoptic nucleus (MPN), of the female rat were studied semi-quantitatively by using a computer-based image analysis system. The area occupied by CGRP- and Met-Enk-IR fibers was significantly increased in the Pe and the MPN after 28-day exposure to E2. Computer-based analysis of CGRP- and Met-Enk-IR fibers in an area of 50-microns intervals from the wall of the third ventricle showed a low flat histogram pattern in ovariectomized rats, but E2 treatment caused a diphasic pattern, corresponding to the Pe and the MPN, respectively. Since the Pe and the MPN contain a high population of estrogen receptors, it is suggested that E2 may have an influence on the neuronal configuration of afferent fibers to these areas. PMID- 1511283 TI - Nerve growth factor increases calcium binding protein (calbindin-D28K) in rat olfactory bulb. AB - Calbindin-D28K (CaBP28K) is a soluble intracellular protein capable of sequestering micromolar concentrations of calcium. The in vivo regulation of CaBP28K by recombinant human nerve growth factor (rhNGF) was studied in adult, male rats. Via Alzet 2002 pumps, each rat received, for 14 days, a lateral ventricle infusion (i.c.v.; n = 5-6/group) of 12 microliters PBS/day containing 1.0 microgram cytochrome C (control) or an equal amount of rhNGF. Six other animals received a vehicle or rhNGF infusion into the central neostriatum. CaBP28K was elevated by 75% (P less than 0.01) in the olfactory bulb following i.c.v. rhNGF in each of two experiments and was not altered in the temporal cortex, hippocampus, olfactory tubercle, cerebellum, or neostriatum. Direct striatal injections of rhNGF did not alter CaBP28K in the neostriatum or other regions (including the olfactory bulb). The increases in olfactory bulb CaBP28K protein levels were verified via Western blot analysis. CaBP28K immunocytochemistry revealed that 33% of olfactory bulb neurons are immunoreactive for CaBP28K and that the number or proportion of immunoreactive neurons did not change with i.c.v. infusions of rhNGF, suggesting that exogenously delivered rhNGF augments the content of CaBP28K in olfactory bulb neurons that normally express the protein. Endogenous NGF may function as a neuroprotective factor by enhancing the ability of these cells to sequester cytoplasmic calcium and retard calcium-mediated neurodegeneration. PMID- 1511284 TI - Thermogenic actions of tryptophan in the rat are mediated independently of 5-HT. AB - Serotonin (5-HT) has been implicated in the central control of energy balance, via inhibition of food intake and stimulation of thermogenesis. Its rate of synthesis in brain is dependent on the availability of its precursor amino acid, tryptophan. The objective of the present study was therefore to investigate the thermogenic actions of tryptophan and to determine whether these actions are mediated by 5-HT. Central or peripheral injections of 5-HT (i.c.v.; 0.5-40 micrograms), 5-hydroxytryptophan (5-HTP) (i.c.v.; 20 micrograms) or tryptophan (i.p.; 20 mg/kg, i.c.v.; 12-60 micrograms) significantly increased resting oxygen consumption (VO2 by approximately 15-20%) in conscious rats, without apparent effects on physical activity. Small increases (5-7%) in VO2 were also observed following peripheral injections of aspartate or glycine (20 mg/kg) but not taurine, whilst central injections of tyrosine or leucine (15-18 micrograms) significantly increased VO2 by 15%. We have previously reported that the thermogenic and anorexic actions of 5-HT are mediated by corticotropin-releasing factor (CRF). In the present study, the thermogenic actions of 5-HTP, like those of 5-HT, were significantly reduced by pretreatment (5 min before) with the CRF antagonist alpha-helical CRF9-41 (25 micrograms, i.c.v.) or a polyclonal antibody to CRF. However, the thermogenic actions of tryptophan were not significantly modified by pretreatment with either the 5-HT antagonist, methysergide (20 micrograms, i.c.v.) or with the CRF antagonist or antibody and thus appear to act through different mechanisms to 5-HT.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1511285 TI - Differences in the number of arginine-vasopressin-immunoreactive neurons exist in the suprachiasmatic nuclei of house mice selected for differences in nest building behavior. AB - Arginine-vasopressin (AVP) is a homeostatic modulator of body temperature during fever and may also be involved in normal body temperature control. In the present study the hypothalamus of mice bi-directionally selected for thermoregulatory nest-building behavior was immunocytochemically labeled for AVP. The low-selected mice had a 1.5-fold higher number of AVP-immunoreactive neurons in the suprachiasmatic nuclei (SCN) compared to the unselected control and the high selected mice. No differences between the selected lines could be detected in the number of AVP-immunoreactive neurons in the paraventricular nuclei (PVN). The neuroanatomical data suggest a possible role of AVP in the SCN and control of thermoregulatory nest-building behavior. Our selected mice may prove to be a model system to study the role of AVP in the SCN. PMID- 1511286 TI - Microdialysis perfusion increases the sensitivity of rat striatal neurons to ischemic insult. AB - Brief periods of global forebrain ischemia which never produced striatal cell loss in control, non-dialyzed striatum resulted in significant cell loss in the contralateral, dialyzed striatum. No striatal cell loss was seen following these short periods of ischemia in animals implanted with dialysis probes that were not perfused. Dialysis perfusion alters striatal extracellular fluid composition in such a way as to render this tissue more sensitive to brief ischemic insult. PMID- 1511287 TI - Regulation of the prefrontal cortical dopamine system by the neuroactive steroid 3a,21-dihydroxy-5a-pregnane-20-one. AB - The dopamine innervation of the prefrontal cortex can be differentiated from other telencephalic dopamine projection fields by its sensitivity to stress. The stress-induced activation of the mesoprefrontal cortical dopamine system can be blocked by pretreatment with benzodiazepines. A group of neuroactive steroids that modulate GABA-induced chloride flux through means distinct from that of the benzodiazepines has recently been identified. Intraventricular administration of the neuroactive steroid 3 alpha,21-dihydroxy-5 alpha-pregnane-20-one resulted in a dose-dependent decrease in dopamine metabolites in the prefrontal cortex, but not in mesolimbic or striatal sites; sedative effects were not observed. Moreover, the neuroactive steroid selectively attenuated the stress-induced activation of the mesoprefrontal cortical dopamine system. These data suggest that neuroactive steroids may function as endogenous anxiolytic agents. PMID- 1511288 TI - Regulation of intracellular free calcium in normal and dystrophic mouse cerebellar neurons. AB - We measured free intracellular calcium ([Ca2+]i) in cultured cerebellar granule cells from normal and mdx mice. Resting levels of ([Ca2+]i) were 24% higher in the dystrophic neurons (normal: 61.2 +/- 1.5 nM calcium, n = 104; dystrophic: 76.1 +/- 2.4 nM calcium, n = 136, P less than 0.01). Dystrophic neurons showed a significantly greater increase in ([Ca2+]i) in the presence of elevated (18 mM) extracellular calcium levels. Resting sodium levels ([Na+]i), however, were found to be similar in normal and dystrophic granule neurons. In addition, sodium influx rates after ouabain inhibition of the Na+/K+ ATPase were also identical. Therefore, the increased permeability of granule neurons was specific to calcium, and did not result from a non-selective cation-permeable conductance. Unlike granule cells, astrocytes do not express dystrophin. Glial cells from normal and dystrophic mice showed no difference in their resting free calcium levels or their response to a high calcium load. Thus, cerebellar granule neurons from mdx mice show a calcium-specific regulatory defect similar to that found in dystrophic muscle fibers, while cerebellar glial cells, which do not normally express dystrophin, have no such defect. PMID- 1511289 TI - Antiestrogen binding sites in brain and pituitary of ovariectomized rats. AB - In addition to interacting with estrogen binding sites in a number of tissues, antiestrogens have recently been shown to interact with a separate, estrogen-non compatible, antiestrogen-specific binding site (AEBS). In order to better understand possible mechanisms by which the antiestrogens may effect behavioral and physiological changes, we have examined AEBS in several areas of the brain and pituitary in adult, ovariectomized rats. Single point binding assays with 2 nM [3H]tamoxifen (TAM) in the presence of saturating amounts (1 microM) E and +/- 1 microM TAM indicated the existence of specific binding to AEBS throughout the brain and pituitary. In most areas of the brain (cortex, cerebellum, amygdala, area postrema/nucleus of the solitary tract region) as well as pituitary. Scatchard analyses revealed the presence of a single AEBS with a dissociation constant (Kd = 1-4 x 10(-9) M) similar to that previously reported for other tissues. However, in both hypothalamus and preoptic area, an additional, higher affinity site (Kd = 6-9 x 10(-11) M) was found. Competitive inhibition studies revealed that there was little competition by the potent estrogen agonist, diethylstilbesterol, for AEBS binding. Antiestrogens competed in the following order: tamoxifen greater than or equal to nafoxidine much greater than keoxifene. Additional competitive inhibition studies were run using neurotransmitter antagonists. The phenothiazines, chlorpromazine and fluphenazine, bind to both D1 and D2 dopamine receptors and effectively compete with [3H]TAM for binding at the AEBS. Other pharmacological substances, including specific antagonists of the D2 sites, as well as antagonists of the norepinephrine, opiate, histamine, GABA and acetylcholine systems, were ineffective competitors for [3H]TAM binding. PMID- 1511290 TI - Regional localization of the regulatory subunit (RII beta) of the type II cAMP dependent protein kinase in human brain. AB - The distribution of the regulatory (RII beta) subunits of type II cAMP-dependent protein kinase in cortical and subcortical areas was examined in human control and Alzheimer's disease (AD) brains. Four monoclonal antibodies generated against bovine brain RII, which cross-reacted with human brain RII beta, detected RII immunoreactivity in pyramidal neurons of the hippocampus and frontal, occipital, parietal and superior temporal cortices and in non-pyramidal neurons of the amygdala and putamen. RII beta immunoreactivity was localized to neuronal perikarya, proximal dendrites and cell processes. With the exception of rare processes in the ventroposterior lateral nucleus, RII-immunoreactivity was not seen in the thalamus. Other areas lacking RII-immunoreactivity included the midbrain, caudate nucleus and globus pallidus. RII-immunoreactivity was not detected in endothelia or glia. Except for the neocortex, the distribution of RII beta immunoreactivity was the same in AD and non-demented control brains; however, cell bodies and their processes stained more intensely and uniformly in the neocortical regions of non-demented controls compared to AD. In the neocortex of AD, RII beta immunoreactivity was substantially decreased in the superior temporal and occipital cortices, but not in the frontal cortex. Our data suggest that RII subunits are regionally distributed in the human brain. RII immunoreactivity was decreased in some regions of neocortex in AD, but it did not preferentially colocalize with neurofibrillary tangles (NFT), senile plaques, or neuropil threads. PMID- 1511291 TI - Prenatal flutamide alters sexually dimorphic nuclei in the spinal cord of male rats. AB - The effects of prenatal exposure to the antiandrogen flutamide on two sexually dimorphic nuclei of the lumbar spinal cord, the dorsolateral nucleus (DLN) and the spinal nucleus of the bulbocavernosus (SNB), were investigated. Rat dams were given daily injections of 5 mg flutamide or vehicle alone from day 11 through 21 of pregnancy. The spinal cords and perineal morphology of their male and female offspring were examined in adulthood. Flutamide reduced the number of SNB and DLN neurons, reduced the somal and nuclear area of SNB neurons, and reduced the weight of the perineal muscles in males. Flutamide produced no effect in females. No sexual dimorphism was found in the mean somal area of DLN neurons, but a sexual dimorphism was found in the distribution of somal areas in our samples; females had proportionately more large neurons than males. Flutamide-treated males also had proportionately more large neurons than control males but fewer than females. A sexual dimorphism was found in the nuclear areas of DLN neurons but flutamide did not influence this trait. PMID- 1511292 TI - Structural modeling of functional visual pathways mapped with 2-deoxyglucose: effects of patterned light and footshock. AB - This paper describes the first application of structural modeling to the visual system. Structural modeling, or path analysis, is a mathematical method that allows for the quantification of the functional strengths of anatomical connections between the structures that form a neural system. The objective was to demonstrate how structural modeling can be used to determine the functional interrelationships between brain structures that form the visual system and how these interrelationships change under different conditions. Data were obtained from measures of 2-deoxyglucose uptake in the visual system of rats presented with either patterned light or darkness. The effects of arousing footshock on visual system operations were also investigated. Models based on the anatomical connections and the interregional correlations between metabolic activity data were used to determine path coefficients representing the magnitude of the influence of each directional path. Statistical evaluation of the models revealed that the dominant positive influences on visual system activity in the darkness were the tectocortical subsystem and the descending connections from secondary visual cortex. In the patterned light model, the total influence of the geniculocortical subsystem was higher than in the dark, and the tectocortical pathways showed both a reduction and a shift in the direction of effects. The models also revealed that the effects of footshock-induced arousal on visual system operations depended upon the visual environment and on extra-visual influences. The footshock led to an increase in the interaction of the two main subsystems at the level of connections between primary visual cortex and the lateral posterior nucleus, and a descending negative influence from the secondary visual cortex became dominant. The models are discussed in the context of conventional analyses to show how structural modeling allows for the determination of much more information about the functional interactions within the visual system of subjects under different experimental conditions. PMID- 1511293 TI - Evidence for a non-genomic action of progestins on sexual receptivity in hamster ventral tegmental area but not hypothalamus. AB - Progestogenic stimulation of both the ventromedial nucleus of the hypothalamus (VMH) and the ventral tegmental area (VTA) is critical for normal receptivity in estrogen-primed hamsters. However, anatomical and biochemical studies have identified very few estrogen-induced progestin receptors in the rodent ventral midbrain. To determine whether progesterone might be working on the membrane of neurons in the VTA, progesterone 3-CMO BSA (P-3-BSA) was applied intracranially. The size of P-3-BSA makes it relatively impermeable to the cell membrane. Ovariectomized hamsters were implanted with 2 chronic cannulae, one aimed at the VMH and the other at the contralateral VTA. These animals were then estrogen primed and tested for sexual receptivity after progesterone-containing tubes were inserted just dorsal to the VMH and P-3-BSA inserts were applied above the VTA. The following week, the hamsters were tested again with the contents of the inserts reversed. Animals with progestogenic stimulation to the VMH and P-3-BSA to the VTA were receptive yet those with P-3-BSA to the hypothalamus and progesterone to the VTA were not receptive. These data suggest that progesterone is capable of facilitating sexual receptivity within the VTA by actions on the cell membrane. The non-genomic effects in the VTA require concurrent genomic activation by progesterone within the hypothalamus. PMID- 1511294 TI - Short-day stimulation of testicular activity and immunoreactivity of the hypothalamic GnRH system in mink following deafferentation of the pineal body by bilateral superior cervical ganglionectomy and melatonin replacement. AB - The effects of superior cervical ganglionectomy on testicular function (testis volume and plasma testosterone levels) and the immunocytochemical activity of the GnRH hypothalamic system were studied in the mink, a short-day breeder. Animals reared in a natural photoperiod were (i) ganglionectomized at four different times during the period extending from the end of summer to the end of autumn (September 15, October 20, October 28, and December 1), and (ii) reared for 50 days in a short gonadostimulatory photoperiod (4L:20D). Lastly, an attempt was made to overcome the effects of superior cervical ganglion removal by administering melatonin to mink reared in a natural photoperiod. In mink reared in a natural photoperiod, deafferentation of the pineal on September 15 (L = 12.5 h) or October 20 (L = 10.5 h) resulted in consistently low values of testicular volume and plasma testosterone until the end of the experiment (February). When the operation was performed on October 28 (L = 10 h) testicular activity was initiated but only lasted a short time and did not allow maximal gonadal development. When superior cervical ganglionectomy was carried out on December 1 (L = 8.5 h), during the phase of renewed testicular activity, the increases in testicular volume and testosterone levels were not affected by the operation and the subsequent variation of these parameters was identical to that observed in intact animals. Similarly, in mink reared for 50 days in a photoperiod of 4L:20D before superior cervical ganglionectomy, deafferentation of the pineal did not prevent gonadostimulation induced by short days.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1511295 TI - Ibotenic acid lesion of the ventral hippocampus differentially affects dopamine and its metabolites in the nucleus accumbens and prefrontal cortex in the rat. AB - To determine the influence of neurons of the ventral hippocampus on dopamine (DA) turnover in other limbic areas, spontaneous and amphetamine-induced locomotion as well as DA and its metabolites were assayed in nucleus accumbens, medial prefrontal cortex and anteromedial striatum, 14 and 28 days after bilateral ibotenic acid (IA) or sham lesions of the ventral hippocampus in the rat. Spontaneous locomotion was increased 28 days postoperatively, while D-amphetamine induced locomotion was augmented both 14 and 28 days postoperatively in IA lesioned animals. DA levels in the nucleus accumbens were decreased on the 14th, but increased on the 28th day after the lesion. Dihydroxyphenylacetic acid (DOPAC), homovanillic acid (HVA) and the DOPAC/DA ratio in the medial prefrontal cortex (MPFC) were reduced 28 days postoperatively. Moreover, there was a significant negative correlation between the DOPAC/DA ratio in the MPFC and DA levels in the nucleus accumbens at this time point. These data indicate that a lesion of the ventral hippocampus can produce differential changes in cortical and limbic DA activity. Implications for an animal model of schizophrenia are considered. PMID- 1511296 TI - Spontaneous recovery of MPTP-damaged catecholamine systems in goldfish brain areas. AB - In goldfish, 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) administered for 3 consecutive days (10 mg/kg), produced a marked decrease in dopamine (DA) and noradrenaline (NA) levels in telencephalon, diencephalon and medulla oblongata, without affecting the serotonin (5-HT) content. Furthermore the neurotoxin decreased either [3H]DA high affinity uptake or K(+)-stimulated DA release from synaptosomal (P2) preparations, with concomitant up-regulation of D2 postsynaptic receptors as well. No significant changes of choline acetyltransferase and glutamic acid decarboxylase activity or [3H]glutamate uptake were observed. Moreover the pretreatment with deprenyl (1 mg/kg) or mazindol (10 mg/kg) but not with clorgyline (5 mg/kg) prevented catecholamine depletion. Added in vitro to synaptosomal preparations both MPTP and more potently MPP+, in a concentration dependent manner, inhibited [3H]DA uptake. Time course study revealed that MPTP induced alteration of neurochemical parameters in goldfish brain areas were almost completely reversed within 6 weeks, suggesting that catecholamine systems in goldfish brain show a remarkable power of recovery after MPTP lesion. PMID- 1511297 TI - Development of MEKA (phosducin), G beta, G gamma and S-antigen in the rat pineal gland and retina. AB - Pinealocytes and retinal photoreceptor cells contain an unusual cytoplasmic complex composed of the G beta gamma dimer of GTP-binding regulatory proteins (G proteins) tightly bound to an acidic 33 kDa phosphoprotein termed MEKA or phosducin; MEKA is a substrate of cyclic AMP-dependent protein kinase. This study characterized the developmental appearance of these and two related proteins, G gamma and S-antigen, in pineal and retinal tissue. MEKA was absent in the pineal gland prior to birth, at a time when it was possible to detect G beta in pineal cytoplasm, indicating that the appearance of G beta in the cytoplasm precedes that of MEKA and does not appear to require the presence of MEKA. The absence of MEKA at this time indicates that the cyclic AMP stimulation of pineal serotonin N acetyltransferase activity is not mediated by MEKA, which has been considered as a possible role of MEKA. After postnatal day 7, pineal MEKA and cytoplasmic G beta increased in a parallel manner, with peak values occurring at about postnatal day 21. Thereafter, both proteins in the pineal gland decreased in a parallel fashion to 10 and 35% of their peak values, respectively; in contrast, the cytoplasmic protein S-antigen and membrane associated G beta remained at maximal levels after this time. Whereas both MEKA and G beta decreased late in development in the pineal gland, these proteins either increased or remained constant in the retina. These tissue-specific patterns were found to differ from those of another cytosolic protein found exclusively in the pineal gland and retina, S-antigen, which remained constant after day 21 in the pineal gland but decreased in the retina late in life. PMID- 1511298 TI - Dioctanoylglycerol stimulates accumulation of [methyl-14C]choline and its incorporation into acetylcholine and phosphatidylcholine in a human cholinergic neuroblastoma cell line. AB - Dioctanoylglycerol, a synthetic diacylglycerol, stimulated [14C]choline uptake in cultured human neuroblastoma (LA-N-2) cells. As this effect has not, to our knowledge, been reported before, it was of interest to characterize it in more detail. In the presence of 500 microM dioctanoylglycerol the levels of [14C]choline attained during a 2 hour labeling period were elevated by 78 +/- 12%, while [14C]acetylcholine and long fatty acyl chain [14C]phosphatidylcholine levels increased by 26 +/- 2% and 19 +/- 5%, respectively (mean +/- S.E.M.). Total (long chain plus dioctanoyl-) [14C]phosphatidylcholine was increased by 198 +/- 33%. Kinetic analysis showed that dioctanoylglycerol reduced the apparent Km for choline uptake to 56 +/- 9% of control (n = 4). The Vmax was not significantly altered. The stimulation of [14C]choline accumulation by dioctanoylglycerol was not dependent on protein kinase C activation; the effect was not mimicked by phorbol ester or by 1-oleoyl-2-acetylglycerol, and was not inhibited by the protein kinase C inhibitors H-7 or staurosporine, or by prolonged pretreatment with phorbol 12-myristate 13-acetate. The effect of dioctanoylglycerol was slightly (but not significantly) reduced by EGTA and strongly inhibited by the cell-permeant calcium chelator bis(o-aminophenoxy) ethane-N,N,N',N'-tetraacetic acid, tetra(acetoxymethyl)ester. Although these results implicate elevated intracellular calcium in the response, dioctanoylglycerol did not increase phosphatidylinositol hydrolysis in LA-N-2 cells, and its effect was not inhibited by the diacylglycerol kinase inhibitor R 59 022 (which blocks the conversion of diacylglycerol to phosphatidic acid, a known stimulator of phosphatidylinositol hydrolysis).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1511299 TI - Intracerebroventricular application of competitive and non-competitive NMDA antagonists induce similar effects upon rat hippocampal electroencephalogram and local cerebral glucose utilization. AB - In this study we have used electrophysiological and metabolic markers to investigate the effects of competitive and non-competitive NMDA antagonists in rats after central or peripheral administration. The non-competitive antagonist, MK-801, induced dose-dependent suppression of rat hippocampal EEG energy both after intraperitoneal (i.p.) and intracerebroventricular (i.c.v.) application. Similar effects were observed after i.p. and i.c.v. application of the competitive antagonist, DL-CPP-ene. Whereas the MK-801 was more potent after i.p. application, DL-CPP-ene was more potent after i.c.v. administration. Intracerebroventricular administration of MK-801 and DL-CPP-ene resulted in similar changes in the pattern of local cerebral glucose utilization in the olfactory tubercle and regions of the limbic system such as the anteroventral thalamus, hippocampus and entorhinal cortex. Intravenous (i.v.) administration of MK-801 induced increases in glucose metabolism similar to those observed after i.c.v. application. In contrast, i.v. administration of DL-CPP-ene induced only small decreases of glucose utilization in several regions of the central sensory system. Thus the blockade of glutamatergic (NMDA) transmission results in decreased hippocampal EEG activity which is paralleled by increased metabolic activity in this area. We conclude from EEG recordings and [14C]2-deoxyglucose uptake experiments that both non-competitive and competitive NMDA antagonists produce the same pattern of alterations after i.c.v. administration. Apparent differences in efficacy after peripheral administration may be largely due to differences in bioavailability. PMID- 1511300 TI - Post-traumatic selective stimulation of glycolysis. AB - Ventilated, chloralose anesthetized cats were subjected to 3.2 atmosphere fluid percussion injury and compared with sham operated controls. In both groups, global cerebral blood flow (CBF), cerebral metabolic rate of oxygen utilization (CMRO2), cerebral metabolic rate of glucose utilization (CMRG1), and 31P magnetic resonance spectroscopy (MRS) determinations of tissue pH (pHi) phosphocreatine (PCr), and inorganic phosphate (Pi) were measured before and 5, 15, 30, and 60 min post-trauma. Following trauma, pH decreased slightly 30 min following trauma and gradually returned to normal. CMRO2, CBF, and arterial pO2 remained at control values throughout the experiment while CMRG1 increased 243% at 5 min post injury then rapidly returned to control values. This combination of acidosis and increased glucose utilization indicates that trauma causes a transient isolated increase in cerebral glycolysis and may be important to consider when investigating the etiology of post traumatic acidosis. PMID- 1511301 TI - Development of neural lobe-like neurovascular contact regions after intrahypothalamic transection of the hypothalamo-neurohypophysial tract. AB - Fifteen days after bilateral transection of the hypothalamo-neurohypophysial tract at the level of the lateral retrochiasmatic area, neurovascular contact regions had developed proximal to 66% of the lesions. Contact regions developed in every case when neural lobe explants were placed into the lesions, and near approximately half of the lesions into which small pieces of sciatic or optic nerve were transplanted. Neurovascular contact regions were characterized by microvascular networks surrounded by dense neurophysin-immunoreactive plexuses. At the fine structural level, the organization of such regions resembled that of the neural lobe, with the single exception that capillaries were not fenestrated. Numerous neurosecretory axons were present, and palisades of neurosecretory axon terminals abutted perivascular basal laminae. Lamellopodia from glial cells partially ensheathed regenerating neurosecretory axons and often lay between terminals and the perivascular basal lamina. Terminals with many microvesicles and few neurosecretory granulated vesicles provided morphological evidence of hormone release. PMID- 1511303 TI - Selective distribution of the 66-kDa neuronal intermediate filament protein in the sensory and autonomic nervous system of the guinea-pig. AB - The immunohistochemical distribution of a recently identified 66-kDa neurofilament protein (NF-66) was investigated in peripheral and autonomic ganglia of the guinea-pig where it has been previously established that other neuronal intermediate filament proteins have a selective distribution. NF-66 immunoreactivity was observed in distinct subpopulations of neurons and did not coexist completely with either the neurofilament triplet or a 57-kDa intermediate filament protein (peripherin). NF-66 labelling was identical to that observed with an antibody to a 150-kDa intermediate filament or associated protein (CH1). These results further demonstrate that different neuronal intermediate filament proteins are present in selective subpopulations of neurons and that these proteins are, therefore, likely to have cell type-specific roles. PMID- 1511302 TI - Functional compartmentalization of energy production in neural tissue. AB - Previous work in our laboratory has shown that neural trauma results in a disparity between oxidative and glycolytic rates. In non-neural tissue, glycolysis and oxidative phosphorylation have been shown to work independently of one another, a phenomenon known as "energy compartmentalization". We believe that functional compartmentalization of energy production may also occur in the brain with glycolysis providing energy for membrane bound ionic pumps. Spreading depression, induced in rodent brain by topical KCl application, results in K+ shifts. The restoration of K+ gradients is accomplished by energy dependent Na(+) K+ pumps. If these pumps depend upon glycolysis, blocking glycolysis should prevent reconstitution of normal [K+]e levels. The present series of experiments were designed to suggest that energy compartmentalization may also exist in brain, and that glycolytic energy production is preferentially used by Na(+)-K+ pumps to maintain normal ionic homeostasis by observing the dynamics of spreading depression induced K+ shifts before and after glycolytic blockade. Spreading depression was associated with increased K+ (48.6 +/- 16.6 mM over control) that normalized within 2.9 +/- 0.3 minutes. Following superfusion with a glycolytic blocking agent, spreading depression produced similar increases in [K+]e (40.6 +/ 12.0 mM over control) but time for reconstitution of the normal [K+]e was 400% longer than controls (2.9 +/- 0.3 to 14.9 +/- 2.1 minutes, P less than 0.001). Time required for recovery of EEG was identical pre- and post-blockade. We believe these data suggest that energy compartmentalization may exist in neural tissue and that glycolytic pathways of energy production are functionally tied to membrane Na(+)-K+ pumps.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1511304 TI - Serotonin preferentially hyperpolarizes capsaicin-sensitive C type sensory neurons by activating 5-HT1A receptors. AB - The effects of serotonin (5-HT) were investigated by intracellular recording from 179 dorsal root ganglion (DRG) cells classified by conduction velocity. Bath applied 5-HT depolarized 82% and hyperpolarized 4% of the A-type cells. In C-type cells, 5-HT depolarized only 41%, but hyperpolarized 39% of the cells. The depolarizing responses were of two types; an increase or decrease in R(in), mediated by 5-HT2or3 receptors, respectively. These receptors were observed in both A- and C-type cells. Hyperpolarizing responses were largely confined to A(delta)- and C-type cells. Carboxamidotryptamine and 8-OH-dipropylamino-tetralin were full agonists in eliciting hyperpolarization, and metitepin, spiperone and spiroxitrine behaved as competitive antagonists. This indicated that hyperpolarization was mediated by a 5-HT1A receptor. A 5-HT1A&3 receptor were found co-localized on some C-type cells. A strong depolarizing response to capsaicin was observed in the subgroup of C-type neurons that were also hyperpolarized by 5-HT. Thus a co-localization of capsaicin and 5-HT1A receptors was also observed. PMID- 1511305 TI - Functional correlates of selective long-term potentiation in the olfactory cortex and olfactory bulb. AB - High-frequency stimulation of the granule cell layer of the olfactory bulb (OB) has previously been shown to result in a selective long-term potentiation (LTP) of late components of potentials evoked in the OB and piriform cortex (PC). The functional impact of this potentiation was explored in male Long-Evans rats with chronically implanted electrodes by comparing the effects of paired-pulse stimulation of the OB in potentiated and control animals. Effects were examined on two components of the potential evoked in the PC: A1, which represents the population EPSP produced by OB mitral cells in PC pyramidal cells via the lateral olfactory tract (LOT), and B1, which represents the subsequent population EPSP produced by PC pyramidal cells in other pyramidal cells. Two separate functional correlates of selective LTP were found. First, there was enhanced paired-pulse depression of B1, indicating increased inhibition of PC pyramidal cells. Second, there was a shift from paired-pulse facilitation to depression of A1, which was accompanied by a decrease in amplitude of the LOT volley, indicating that fewer mitral cells were activated by the stimulation. This shift was most prominent in animals with stimulating electrodes closest to the mitral cell layer, suggesting that it is dependent upon direct stimulation of mitral cell somata. These observations, together with other results reported in the manuscript, support the conclusion that there is an enhanced inhibition of mitral cells following selective LTP. Thus a primary consequence of selective LTP appears to be enhanced inhibition of principal neurons in both the PC and OB. These findings are consistent with our previous proposal that selective LTP represents potentiation at excitatory synapses made by PC pyramidal cells on inhibitory interneurons in the PC and OB. PMID- 1511306 TI - Transforming growth factor-beta 1 differentially regulates proliferation and MHC class-II antigen expression in forebrain and brainstem astrocyte primary cultures. AB - To facilitate investigation of cytokine regulation of reactive astrogliosis, primary astrocyte cultures from neonatal murine forebrain and brainstem were established. Forebrain and brainstem astrocytes proliferated at a similar rate under basal culture conditions, and both were growth-inhibited by treatment with recombinant murine interferon-gamma. The growth of cultured brainstem astrocytes was significantly enhanced by exposure to recombinant human transforming growth factor-beta 1. In contrast, proliferation of forebrain astrocytes was not significantly affected by transforming growth factor-beta 1. The disparate responses of brainstem and forebrain astrocytes to transforming growth factor beta 1 treatment were not limited to effects on cell growth, since transforming growth factor-beta 1 could block interferon-gamma-induced MHC class-II antigen expression on cultured brainstem astrocytes but not on forebrain cells. Results could not be attributed to use of an heterologous cytokine/cellular target system, since similar variability in transforming growth factor-beta 1 modulation of major histocompatibility complex antigen expression could be demonstrated using two human astrocytoma cell lines. This report is the first to document mitogenic response to transforming growth factor-beta 1 for neuroepithelial cells. The role of transforming growth factor-beta 1 in regulating aspects of reactive astrogliosis, particularly in the context of inflammatory demyelination, requires further investigation. Furthermore, these studies may provide insight into regional variability in the sequelae of inflammation within the central nervous system. PMID- 1511307 TI - Two types of neuroplasticities in the kindling phenomenon: effects of chronic MK 801 and methamphetamine. AB - Using the low-frequency kindling technique, we studied the effects of chronic MK 801 and chronic methamphetamine (MAP) administration on hippocampal kindling seizure development. In experiment 1, MK-801 (0.05, 0.1 mg/kg i.p.) was administered 2 h before each electrical stimulation until kindling developed into stage-3 seizure. In experiment 2, we started daily electrical stimulations two weeks after the last injection of chronic MAP administration (6 mg/kg/day, 14 days). The number of stimulating pulses required for the triggering of epileptic afterdischarge (pulse-number threshold, PNT) was used as an indicator of the seizure threshold. PNT, afterdischarge duration (ADD) and behavioral seizure stage (BSS) of each induced seizure in the initial stage of kindling; the kindling rates for stage 3 and stage 5 seizures; seizure parameters at the completion of kindling of the drug-treated groups were recorded and compared to the values of each saline-treated control group. Our result showed that MK-801 administration prior to each electrical stimulation selectively and significantly increased PNT in the initial stage of kindling without affecting other seizure parameters. Chronic pretreatment of MAP caused a selective and significant decrease of PNT of the first two stimulations in the kindling process. Taken together with the previous studies, these results suggest that long-term potentiation plays an important role in the development of the excitability of seizure focus but not of the induced seizure's propagation in the hippocampal kindling phenomenon. Clinically MK-801 seems to be a more efficacious drug in preventing the induction of seizures than in suppressing the acquired seizures. PMID- 1511309 TI - Peripheral control of the antagonist muscle during unexpectedly loaded arm movements. AB - Ten subjects completed a series of goal-directed arm flexion movements unexpectedly perturbed by three different types of mechanical load. Examination of electromyograph (EMG) waveforms and kinematic information collected during randomly distributed test trials facilitated investigation into the interaction between loading conditions and the response-associated EMG innervation patterns. Results of the EMG waveform analysis revealed that inertial and spring loads produced cocontraction and triphasic activation patterns, respectively. Unexpected application of a stretched-spring load, which produced a change in initial torque values without changing the rate of loading, also resulted in the use of a triphasic activation pattern. These different EMG patterns were observed while movement displacement for all three loads fell within the limits of the target area. PMID- 1511308 TI - Effects of septal and/or raphe cell suspension grafts on hippocampal choline acetyltransferase activity, high affinity synaptosomal uptake of choline and serotonin, and behavior in rats with extensive septohippocampal lesions. AB - At 31 days of age, Long-Evans female rats sustained aspirative lesions of the septohippocampal pathways and, 14 days later, received intrahippocampal suspension grafts prepared from the region including the medial septum and the diagonal band of Broca (Group S, n = 11), from the region including the mesencephalic raphe (Group R, n = 11) or from both regions together (Group S+R, n = 11). Sham-operated (Group Sham, n = 9) and lesion-only (Group Les, n = 11) rats served as non-grafted controls. Seven Sham, 7 Les and 8 rats from each transplant group were tested for home cage activity (6 months after grafting) and radial maze performance (between 7.5 and 8.5 months post-grafting). One month after completion of behavioral testing, the dorsal hippocampi of these rats were prepared for measuring choline acetyltransferase (ChAT) activity and high affinity synaptosomal uptake of both [3H]choline and [3H]serotonin. The remaining rats were used for histological verifications on brain sections stained for acetylcholinesterase (AChE). The lesions increased locomotor activity, impaired radial maze learning and, in the dorsal hippocampus, reduced AChE positive staining, decreased ChAT activity (-73%) as well as high affinity uptake of both choline (-81%) and serotonin (-82%). Neither type of transplant produced any significant behavioral recovery. However, septal transplants increased hippocampal AChE positivity, restored ChAT activity and enhanced choline uptake to 116% and 70% of the values found in sham-operated rats, respectively; they had no significant effect on uptake of serotonin. Transplants from the raphe region had weak effects on hippocampal AChE positivity, increased both the ChAT activity and the choline uptake to 70% ad 38% of the sham-operated rats, respectively, and produced an (over)compensation of the serotonin uptake which reached 324% of the values found in sham-operated rats. The co-transplantation of both regions resulted in restoration of ChAT activity (113% of sham-operated rats values), choline uptake (83% of sham-operated rats) and serotonin uptake (129% of sham operated rats). Our neurochemical data show that after extensive denervation of the hippocampus, intrahippocampal grafts of fetal neurons may foster a neurotransmitter-specific recovery which depends upon the anatomical origin of the grafted cells: a graft rich in serotonergic neurons overcompensates the serotonergic deficit, a graft rich in cholinergic neurons attenuates the cholinergic deficit, whereas a mixture of both types of grafts produces recovery from both types of deficits. Thereby, both the feasibility and the interest of the co-grafting technique are confirmed.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1511310 TI - Recovery of consummatory feeding behavior after bilateral lesions of the cerebral buccal connectives in Aplysia californica. AB - In the sea hare, Aplysia californica, consummatory feeding behavior is selectively abolished by bilateral crushes of the cerebral-buccal connectives and recovers by postlesion day 13. Recovered biting responses are initially weak and increase in magnitude gradually with time. The lesions do not affect appetitive feeding behavior or unrelated reflexive behaviors. Thus, feeding in Aplysia can be used to examine the neural basis of behavioral recovery after CNS injury. PMID- 1511311 TI - The action of CGS-19755 on the redox enhancement of NMDA toxicity in rat cortical neurons in vitro. AB - The effects of the competitive N-methyl-D-aspartate receptor antagonist CGS-19755 (cis-4-phosphonomethyl-2-piperidine carboxylic acid) were studied in cultures of rat cerebral cortex under normal and altered redox conditions. CGS-19755 was effective in preventing delayed neuronal death produced by an acute exposure to either glutamate (500 microM) or NMDA (200 microM), but was ineffective in protecting neurons against the toxicity induced by a prolonged exposure to kainate (500 microM). We observed that the reducing agent dithiothreitol (DTT, 500 microM), could dramatically enhance toxicity and electrophysiological responses produced by 50 microM NMDA. CGS-19755 (100 microM) could effectively block both of these effects of DTT. Any toxicity produced by DTT alone was also antagonized by CGS-19755. In contrast, oxidized DTT did not enhance NMDA toxicity nor was it toxic when added alone. These results indicate that CGS-19755 is an effective and specific neuroprotectant acting at the NMDA receptor in vitro, and that the enhancement in NMDA toxicity induced by DTT is mediated by an increase in activity at this receptor complex. PMID- 1511312 TI - Synaptic inhibition of accessory motoneurons evoked by stimulation of the trigeminal nerve in the cat. AB - Stimulation of the trigeminal nerve produced polysynaptic inhibitory postsynaptic potentials (IPSPs) in accessory motoneurons of the cat. This contrasts with the observation that dorsal cervical motoneurons responded with EPSPs to trigeminal stimulus. Stimulation of the rostral part of spinal trigeminal nucleus elicited di- or polysynaptic IPSPs in accessory motoneurons. Transection of the anterior funiculus at the upper cervical cord selectively abolished the IPSPs. The IPSPs were antagonized by systematically administrated strychnine but not bicuculline. PMID- 1511313 TI - Regulation of glucocorticoid receptor immunoreactivity in the rat hippocampus by androgenic-anabolic steroids. AB - To determine whether androgenic-anabolic steroids (AAS) regulate glucocorticoid receptors (GR), the effects of a mixture of three commonly abused AAS (testosterone cypionate, nandrolone decanoate and boldenone undecylenate) on GR immunoreactivity (ir), were examined in hippocampi of adrenalectomized male rats. Treatment with AAS for 1 week increased nuclear GRir in pyramidal cells of CA1, and granule cells of the dentate gyrus. These findings suggest a role for GR in the mediation of some of the CNS effects of androgenic-anabolic steroids. PMID- 1511314 TI - Effects of central administration of opioids on facial scratching in monkeys. AB - Epidural and intrathecal administration of opioids to humans can produce facial pruritus and scratching that is naloxone reversible. It has been proposed that opioids may act at the level of the medulla to produce facial pruritus and associated scratching behavior. We investigated the effects of mu, delta and kappa opioid-receptor agonists microinjected unilaterally into the medullary dorsal horn (MDH) on facial scratching in cynomolgus monkeys. The selective mu opioid-receptor agonist, DAMGO (3.1-25.0 ng) produced large dose-dependent, naloxone-reversible increases in facial scratches. The selective delta opioid receptor agonist, DPDPE (1.0-5.0 micrograms) and the selective kappa opioid receptor agonist, U-50,488H (0.1-5.0 micrograms) did not produce significant increases in facial scratching behavior. We conclude that the MDH is a site where DAMGO, a mu opioid-receptor agonist, can act to produce facial scratching in monkeys, and that the MDH is likely the site where centrally administered opioids act to produce facial pruritus in humans. PMID- 1511315 TI - Optic nerve regeneration with return of vision through an autologous peripheral nerve graft. AB - The optic fiber termination layer in the contralateral optic tectum was reinnervated and useful vision was recovered in the adult frog, after successful optic nerve regeneration through an autologous peripheral nerve-bridge used to replace the optic nerve and optic chiasma. During their course through the nerve bridge, the optic fibers were associated with Schwann cells in the usual relationship observed in peripheral nerve. PMID- 1511316 TI - Effects of combined methysergide and mecamylamine/scopolamine treatment on spatial navigation. AB - In the present study, we investigated the effects of a 5-HT2 receptor antagonist, methysergide (2.5, 7.5 and 20 mg/kg), on spatial learning in saline, mecamylamine (10 mg/kg) and scopolamine (0.8 mg/kg) treated rats. Methysergide had no effect on water-maze (WM) spatial learning in rats subjected to saline or mecamylamine pretreatments. However, scopolamine-induced WM learning deficit was augmented by methysergide at doses of 7.5 and 20 mg/kg. These results further suggest (A) that cholinergic and serotonergic systems may interact in the regulation of spatial learning, and (B) that the cholinergic component of this interaction with serotonin2 receptors is mediated by muscarinic receptors, but not by nicotinic receptors. PMID- 1511317 TI - Enduring suppression of hippocampal long-term potentiation following traumatic brain injury in rat. AB - This study investigated changes in synaptic responses (population spike and population EPSP) of CA1 pyramidal cells of the rat hippocampus to stimulation of the Schaffer collateral/commissural pathways 2-3 h after traumatic brain injury (TBI). TBI was induced by a fluid percussion pulse delivered to the parietal epidural space resulting in loss of righting responses for 4.90-8.98 min. Prior to tetanic stimulation, changes observed after the injury included: (1) decreases in population spikes threshold but not EPSP thresholds; (2) decreases in maximal amplitude of population spikes as well as EPSPs. TBI also suppressed long-term potentiation (LTP), as evidenced by reductions in post-tetanic increases in population spikes as well as EPSPs. Since LTP may reflect processes involved in memory formation, the observed suppression of LTP may be an electrophysiological correlate of enduring memory deficits previously demonstrated in the same injury model. PMID- 1511318 TI - Demonstration of artifactual coupling between spinal neurons and glial cells during intracellular recording with micropipette electrodes. AB - Intracellular recordings with electrophysiological properties that are characteristic of both neurons and glial cells were obtained in the isolated spinal dorsal horn. Intracellular staining supports an idea that these elements may become artifactually coupled via the recording electrode. This coupling can be a gradual process, occurring over periods up to 30 min, and may have implications for the interpretation of slow, afferent-evoked potentials in some dorsal horn neurons. PMID- 1511319 TI - High affinity [3H]ryanodine binding sites in postmortem human brain: regional distribution and effects of calcium, magnesium and caffeine. AB - The pharmacological properties, regional distribution and autoradiographic localization of [3H]ryanodine binding sites were examined in postmortem human brain. Analyses of binding data from labeled ryanodine titration experiments conducted in frontal cortex revealed a single class of high affinity binding sites with a Kd value of 3.6 nM and a Bmax value of 99 fmol/mg protein. In unlabeled ryanodine titration experiments, Kd and Bmax values were 6.5 nM and 132 fmol/mg protein, respectively. Binding was found to be dependent on free Ca2+ (ED50 value, 89 microM) and was decreased by 35% in the presence of 5 mM Mg2+. This Mg2+ inhibition was abolished by the addition of 10 mM caffeine. Analysis of the regional distribution of [3H]ryanodine binding in membrane preparations revealed high levels of sites in putamen and caudate nucleus, intermediate levels in hippocampus and cortex, and low levels in cerebellum. Autoradiographically, the hippocampus displayed a high density of binding sites in the CA3 region and the dentate gyrus. Ryanodine binding sites in human brain exhibit similar, but not identical binding and pharmacological characteristics to ryanodine receptors previously identified in muscle and more recently in rat and rabbit brain and accordingly may be involved in the regulation of intracellular calcium. PMID- 1511320 TI - Basic fibroblast growth factor (bFGF) immunolocalization in the rodent outer retina demonstrated with an anti-rodent bFGF antibody. AB - The distribution of bFGF in mouse and rat retinas was established using an antibody generated against a rat specific bFGF sequence. The patterns established with this antibody were distinctly different in comparison to the immunostaining patterns using antibodies prepared against similar regions of bovine and human bFGF sequences. Using the anti-rat antibody, at postpartum day 5, both species demonstrate bFGF-like labeling in the outer retina, primarily associated with developing photoreceptors. The anti-rat bFGF antibody in the adult mouse produces intense labeling at the level of the photoreceptor outer segment, whereas in the adult rat, Muller's cells and RPE were intensely labeled but the photoreceptors appeared to be unlabeled. In contrast, the bovine and human antibodies consistently label ganglion cells in both mouse and rat retinas, cells in the inner aspect of the inner nuclear layer and developing horizontal cells, whereas no photoreceptor labeling was observed. These results suggest that minor species differences in a short segment of the bFGF molecule used to generate these antibodies may result in major differences in apparent bFGF-like immunolocalization. PMID- 1511321 TI - Puberty acceleration in female mice induced with a partially purified male urine extract: effects on catecholamine release from the olfactory bulbs and hypothalamus. AB - In the present experiment peri-pubertal female mice were treated with a partially purified puberty accelerating urine extract (PAUE). Mice treated with the PAUE showed an advance in the onset of puberty as indicated by significantly increased uterine weights. Treatment with the PAUE did not alter basal or potassium- (K+, 30 mM) stimulated release of catecholamines (dopamine or norepinephrine) from either anterior or posterior superfused olfactory bulb tissue fragments. There was, however, an overall significantly greater amount of basal and K(+) stimulated release of NE from the posterior vs. the anterior olfactory bulb. Potassium-stimulated-, but not basal, release of catecholamines from the medial basal hypothalamus of PAUE-treated female mice were increased, with dopamine showing a statistically significant difference compared to water-treated females. These data demonstrate that treatment with the PAUE is a very effective means to accelerate the onset of puberty and results in accompanying increases in catecholaminergic activity, in particular dopamine, within the medial basal hypothalamus. PMID- 1511323 TI - Structural asymmetry in the thalamofugal visual projections in 2-day-old chick is correlated with a hemispheric difference in synaptic density in the hyperstriatum accessorium. AB - Differences in visual discrimination ability between the left and right eyes of chicks, which are most prominent in young males, may result from a structural asymmetry in the organization of the visual projections from the thalamus to the visual Wulst. This asymmetry in projections is no longer present by 21 days in males when the contralateral projections from the right thalamus to the left hyperstriatum have developed. Since the asymmetry of the thalamo-hyperstriatal system results in a differential input of fibres to regions of the hyperstriatum which in turn project to the hyperstriatum accessorium (HA), one of the major differences expected within this region would be an asymmetry in the numerical density of synapses (Nv.syn/microns3). When this was examined in the hyperstriatum accessorium of 2-day-old male chicks, the density of synapses in the right HA was found to be significantly higher (22%, P less than 0.05) than in the left HA. The consequences of this asymmetry in synaptic density in the HA could be widespread and influential within the chick visual system. PMID- 1511322 TI - Characterization and distribution of angiotensin II binding sites in fetal and neonatal astrocytes from different rat brain regions. AB - Although angiotensin II (Ang II) binding sites have been extensively investigated in brain, revealing the presence of both AT1 and AT2 subtypes in various areas, the question as to which cells express AT1 and AT2 sites is still open. We report here that primary cultures of astrocytes obtained from various brain regions of fetal (F17) and one-day-old rats express Ang II binding sites belonging only to the AT1 subtype. The binding sites have the same binding profile in all regions tested; however, much less binding was observed in membranes of astrocytes derived from cortical than from subcortical regions and almost none were found in neonatal cortex. In addition, the dispersion method used at the onset of culture affects the number of binding sites present at the end of the culture period. PMID- 1511324 TI - Lewy bodies contain beta-amyloid precursor proteins of Alzheimer's disease. AB - To assess the contribution of Alzheimer's disease amyloid proteins to cortical and substantia nigra Lewy bodies (LBs), regions of postmortem brain rich in intraneuronal LBs were examined immunohistochemically. Antibodies to epitopes in domains outside the amyloidogenic beta-amyloid peptide (BAP) in BAP precursor proteins (BAPPs) as well as to the BAP itself were used as probes. These studies showed that only BAPP epitopes outside the BAP were present in substantia nigral and cortical LBs. Thus, non-amyloidogenic domains of BAPPs may be associated with intraneuronal inclusions comprised of neurofilament proteins. PMID- 1511325 TI - Postnatal exposure to tones alters the tuning characteristics of inferior collicular neurons in the rat. AB - Young rats were exposed to either a 4 or 20 kHz steady tone during the first 3 weeks after birth, and then single unit responses to pure tones were studied at their inferior colliculi (IC). The best frequencies (BF's) of the cells showed strong clustering around the frequency of exposure. PMID- 1511326 TI - Divergent effects of deep cerebellar lesions on two different conditioned somatomotor responses in rabbits. AB - Rabbits with bilateral lesions involving either the anterior interpositus nucleus or the superior cerebellar peduncle were subjected to appetitive Pavlovian conditioning training involving repeated pairings of a 2-s tone with an intraoral pulse of water. Such training resulted in the rapid development of robust, anticipatory jaw-movement responses (JM CRs) to the tone, and, in fact, the performance levels exhibited by lesioned animals did not differ significantly from those observed in sham-operated control animals. Additional experiments involving unpaired tone/water presentations confirmed the associative character of the JM CRs. On the other hand, lesioned animals exhibited severe bilateral performance deficits when later subjected to aversive eyeblink conditioning procedures, consistent with previous findings. The present results thus suggest that the interpositus nucleus is not an essential neural substrate for the development of appetitively conditioned masticatory responses. PMID- 1511327 TI - Reappearance of calcitonin gene-related peptide-like immunoreactivity in the dorsal horn in the long-term dorsal root transected rat. AB - Calcitonin gene-related peptide (CGRP)-immunoreactive (IR) fibers in the rat dorsal horn superficial laminae vanish almost completely 3 weeks following unilateral dorsal rhizotomy. After a prolonged survival (20 weeks) of dorsal rhizotomy there is, however, a reappearance of CGRP-IR fibers in the corresponding laminae of the dorsal horn. The density of such IR fibres showed a clear gradient with the lowest number found in the midlesion region and an increase in density towards the neighboring, intact segments. In normal as well as lesioned rats, no neurons intrinsic to the dorsal horn contained detectable levels of CGRP-like immunoreactivity (LI). Furthermore, no cells could, by use of in situ hybridization, be demonstrated to contain detectable levels of mRNA encoding for CGRP in the dorsal horn. Based on these findings, we suggest that the CGRP-IR fibers observed following long-term survival of dorsal rhizotomy derive from proliferating collateral branches of primary afferents of neighboring intact segments. PMID- 1511328 TI - Intracellular signalling systems controlling the 5 alpha-reductase in glial cell cultures. AB - Glial cells are able to metabolize testosterone into DHT through the action of the enzyme 5 alpha-reductase. DHT may be further processed to 3 alpha-diol by the 3 alpha-hydroxysteroid-dehydrogenase. The aim of this study was to analyze if a modulation of two second messenger systems might be able to modify the 5 alpha reductase and the 3 alpha-hydroxysteroid-dehydrogenase activities present in glial cells. To this purpose, the formation of DHT has been measured in rat glial cell cultures after different time of exposure to TPA, 4 alpha-Ph, an active and an inactive phorbol ester respectively, and 8-Br-cAMP. The results obtained indicate that the formation of DHT is not modified by the addition of phorbol esters. On the contrary, a statistically significant increase of 5 alpha reductase activity, over control levels, has been observed after 6, 12, and 24 h of incubation with 8-Br-cAMP (10(-3) M). The effect of the cAMP analogue appears to be specific for the 5 alpha-reductase, since the 3 alpha-hydroxysteroid dehydrogenase did not show any variation after exposure to the drug. In conclusion, the present data suggest that proteinkinase A (PKA) might be involved in the control of the 5 alpha-reductase in glial cells. It is postulated that nervous inputs utilizing cAMP as the second messenger might modify the activity of this enzyme in glial cells. PMID- 1511329 TI - Differential actions of acetylcholinesterase on the soma and dendrites of dopaminergic substantia nigra neurons in vitro. AB - In the substantia nigra, acetylcholinesterase (AChE) has non-cholinergic action on dopaminergic neurons. The subset of neurons particularly sensitive to AChE are characterized by functionally active apical dendrites extending into the pars reticulata and generating a powerful calcium conductance. This study thus attempted to establish directly the importance of these dendrites regarding the action of AChE. Segregation of the pars compacta from the pars reticulata did not affect the AChE-induced hyperpolarization on this sub-set of dopaminergic neurons. However, the ionic basis of the hyperpolarization was related to the integrity of the neurons: AChE caused an opening of potassium channels in intact cells. On the other hand when the pars reticulata containing apical dendrites was removed, an action of AChE involving the closure of calcium/sodium channels was revealed. The results demonstrate that the net effect of AChE need not be related to any particular segment of the dopaminergic neurons, whereas the nature of the mechanism underlying that effect depends on the presence, or otherwise, of the apical dendrites. PMID- 1511330 TI - Fluoxetine attenuates the DL-fenfluramine-induced increase in extracellular serotonin as measured by in vivo dialysis. AB - Rats with hippocampal dialysis probes were treated with DL-fenfluramine (FEN), fluoxetine, or FEN with fluoxetine pre-treatment. FEN (12.5 mg/kg) increased extracellular serotonin (5-HT) from 0.4 +/- 0.04 to 25.2 +/- 4.16 pg/10 microliters. Fluoxetine (10.0 mg/kg) increased extracellular 5-HT levels from 0.4 +/- 0.05 to 2.4 +/- 0.33 pg/10 microliters. FEN-induced increases in extracellular 5-HT were attenuated by 66% with fluoxetine pre-treatment. This result supports the view that the 5-HT releasing properties of FEN are mediated by the 5-HT uptake transporter. PMID- 1511331 TI - Electron microscopic identification of lamina I axon terminations in the nucleus submedius of the cat thalamus. AB - Ascending lamina I axons were labeled with Phaseolus vulgaris leucoagglutinin and the synaptic connections of their terminals in nucleus submedius (Sm) were studied in the electron microscope. The terminals were large, contained rounded synaptic vesicles, and were involved in complex synaptic aggregations with pre- and postsynaptic dendrites. It was observed that clustered large boutons from a single axon could contact a single dendritic shaft. These observations support a sensory role for lamina I input to Sm. PMID- 1511332 TI - Axon types classified by morphometric and multivariate analysis in the rat optic nerve. AB - Calibers of the rat optic nerve axons distribute unimodally and it is difficult to distinguish groups among them. However, these fibers arose from 3 types of ganglion cells and showed 3 conduction velocities. Performing a cluster analysis over several ultrastructural parameters we found 3 main groups of fibers. These groups are present in a very similar proportion to the ganglion cells groups described in the rat retina. PMID- 1511333 TI - Enhanced responses of nucleus accumbens neurons in male rats to novel odors associated with sexually receptive females. AB - One group of male rats was trained to associate novel odors with three different environmental conditions: the presence of (i) a sexually receptive female (RF), (ii) an unreceptive female (UF) and (iii) no other rat (NO). A second group of males received no training. Single units in nucleus accumbens (NAC) were then recorded in anesthetized animals and their responsiveness to various odors was tested. Odors that had been associated with receptive females during training evoked significantly more unit responses in NAC than did the same odors in untrained males. There were no differences between trained and untrained males in the numbers of units responsive to odors associated with unreceptive females and with the empty training chamber. In trained animals, both the percentage of responding units and the magnitude of olfactory-evoked responses were significantly larger with RF-associated odors than with either UF or NO odors. Both of these effects were more pronounced in rats that had ejaculated with females during training than in rats that had not. Findings demonstrated that pairing odors with the presentation of sexually receptive females enhanced the responsiveness of NAC neurons to those odors and indicated a role for NAC in associating environmental stimuli with natural reward processes. PMID- 1511334 TI - The cell recognition molecule, cognin, mediates choline acetyltransferase activity in embryonic chick retina. AB - Cell signaling and cell-cell interactions play an important role in neuronal differentiation in the embryonic CNS. Previous work (Hausman, R.E., Vivek Sagar, G.D. and Shah, B.H., Dev. Brain Res., 59 (1991) 31-37) had shown that cholinergic differentiation in the embryonic chick retina depends on insulin and neuron neuron interactions. Here, we pursued the molecular nature of that dependence on cell interactions. The embryonic chick retina is known to contain several cell adhesion or recognition molecules. We asked if retina cognin, a 50 kDa cell surface-associated protein, played a role in controlling cholinergic differentiation in the developing chick retina. As previously, cholinergic differentiation was measured by two markers: choline acetyltransferase (ChAT) activity and high-affinity choline uptake. We used polyclonal antibody to cognin to determine if blocking cognin-mediated cell interactions would affect the normal embryonic increases in these cholinergic markers. We demonstrated a 40% inhibition of the normal developmental appearance of ChAT activity in retina neuronal cultures from early development, but no effect in cultures from more differentiated retina. The inhibition was selective for retina, since it was not seen in neural tissues like cerebrum and cerebellum that also express ChAT. In contrast to the effect of insulin, choline uptake was not affected by treatment with cognin antibody. Antibodies to two other cell recognition molecules present in the retina (Ng-CAM and N-cadherin) did not block the normal developmental appearance of ChAT. These results suggest that cognin-mediated interactions play a unique role in the control of one aspect of cholinergic differentiation in the developing chick retina. PMID- 1511335 TI - Inhibition of a cutaneous nociceptive reflex by a noxious visceral stimulus is mediated by spinal cholinergic and descending serotonergic systems in the rat. AB - The present study examined the spinal pathway and receptors that mediate nocigenic inhibition of the tail-flick (TF) reflex produced by conditioning colorectal distension (CRD). Conditioning CRD (80 mmHg; 30 s) inhibited the TF reflex in all rats studied (n = 29). In 19 rats where intensity-dependent effects of CRD were studied, conditioning CRD in 7 rats facilitated the TF reflex at lesser, non-noxious intensities (mean 7.9 +/- 2.1 mmHg) and inhibited the TF reflex at greater, noxious intensities (40-100 mmHg); conditioning CRD at all intensities tested only inhibited the TF reflex in the other 12 rats. Inhibition of the TF reflex produced by 30 s CRD was short-lasting, repeatable and graded with the intensity of CRD. The mean threshold of CRD for inhibition of the TF reflex to cut off (10 s) was 61.4 +/- 3.3 mmHg (n = 29). Intrathecal pretreatment with atropine or methysergide significantly attenuated the inhibitory effect of CRD on the TF reflex; the effects were time- and dose-related. Intrathecal pretreatment with mecamylamine, phentolamine or naloxone was without effect. Intrathecal administration of physostigmine, an acetylcholinesterase inhibitor, significantly reduced the threshold intensity of conditioning CRD necessary to inhibit the TF reflex to cut off (mean 36.0 +/- 4.0 mmHg; n = 5). Bilateral transections of the spinal dorsolateral funiculi (DLF) did not affect the inhibitory effect of CRD in 4/7 rats and attenuated the inhibitory effect of CRD in the other 3 rats. The antagonistic effect of methysergide on CRD-produced inhibition of the TF reflex was abolished following the DLF transections, while scopolamine retained its efficacy in rats with bilateral DLF transections. These findings provide evidence for involvement of spinal cholinergic interneurons as well as a descending serotoninergic pathway traveling in the DLF in CRD-produced inhibition of the TF reflex. PMID- 1511336 TI - Vagal afferent-mediated inhibition of a nociceptive reflex by i.v. serotonin in the rat. II. Role of 5-HT receptor subtypes. AB - In the rat, intravenous (i.v.) serotonin (5-HT) is a noxious stimulus which produces distinct vagal afferent-mediated pseudoaffective responses, a passive avoidance behavior, a vagal afferent-mediated inhibition of the nociceptive tail flick (TF) reflex and a complex triad of cardiovascular responses. In the present study, we have used a variety of 5-HT receptor antagonists to characterize the receptor subtype(s) in the rat that mediate (1) inhibition of the TF reflex and (2) the cardiovascular responses produced by i.v. 5-HT. 5-HT produced a dose dependent (3-72 micrograms/kg, i.v.) inhibition of the TF reflex (ED50 = 15.3 +/- 0.7 micrograms/kg). Following administration of the 5-HT2 receptor-selective antagonists ketanserin (50-250 micrograms/kg, i.v.) or xylamidine (10-100 micrograms/kg, i.v.), or the 5-HT3 receptor-selective antagonists ICS 205-930 (50 250 micrograms/kg, i.v.) or MDL 72222 (25-250 micrograms/kg, i.v.), there appeared to be a parallel shift of the 5-HT dose-response curve to the right. Following co-administration of xylamidine (50 micrograms/kg, i.v.) with ICS 205 930 (100 micrograms/kg, i.v.), the 5-HT-induced inhibition of the TF reflex was completely abolished at all doses of 5-HT tested (3-288 micrograms/kg, i.v.). In contrast, administration of the centrally acting 5-HT2 receptor-selective antagonist LY 53857 (10-100 micrograms/kg, i.v.) or the non-specific receptor antagonist methysergide (25-500 micrograms/kg, i.v.) resulted in a dose dependent, but not parallel shift of the 5-HT dose-response curve to the right. The maximal doses of LY 53857 and methysergide tested (250 micrograms/kg and 500 micrograms/kg, respectively) completely abolished the effects of 5-HT (3-288 micrograms/kg, i.v.). Administration of the alpha 1-adrenoceptor antagonist prazosin (25-100 micrograms/kg, i.v.) failed to alter the 5-HT dose-response curve, indicating that the effects of ketanserin were due to blockage of 5-HT2 receptors rather than alpha 1 receptors. Administration of each of the antagonists also produced marked, but selective effects on components of the complex cardiovascular response to i.v. 5-HT. Each of the 5-HT3 receptor selective antagonists (ICS 205-930 or MDL 72222) produced a dose-dependent attenuation of the Bezold-Jarisch reflex-mediated hypotension and bradycardia, and each of the 5-HT2 receptor selective antagonists (xylamidine, ketanserin or LY 53857) produced a dose-dependent attenuation of the pressor response. The non specific 5-HT receptor antagonist methysergide produced a dose-dependent attenuation of the 5-HT-induced pressor response.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1511337 TI - Transferrin receptors of rat and human brain and cerebral microvessels and their status in Alzheimer's disease. AB - We studied the regional distribution of specific [125I]transferrin binding to transferrin receptors in the brains and cerebral microvessels of humans and rats. We also assessed transferrin receptors in subjects with Alzheimer's disease. Human diferric [125I]transferrin bound to regional brain and cerebral microvessels with high affinity (dissociation constants of 1-10 nM), and the maximal binding densities ranged from 30 to 90 pmol/mg protein in the brain and were several-fold higher in cerebral microvessels. In Alzheimer's disease, transferrin receptor densities were significantly reduced in the hippocampus and the temporal and occipital cortex but were unchanged in the frontal and parietal cortex and the cerebellum. Although [125I]transferrin binding was higher in cerebral microvessels from subjects with Alzheimer's disease than in those of age matched controls, this difference did not attain statistical significance. These results suggest that transferrin receptor density was decreased in some cortical areas including the hippocampus in Alzheimer's disease but relatively unchanged in cerebral microvessels. PMID- 1511338 TI - Evidence that cholecystokinin-enhanced retention is mediated by changes in opioid activity in the amygdala. AB - Mice, partially trained to avoid footshock in a T-maze, showed enhanced retention relative to vehicle-injected mice when treated peripherally with arecoline, D amphetamine, cholecystokinin octapeptide (CCK-8), epinephrine or naloxone. Both intra-amygdaloid and intraventricular injections of beta-endorphin resulted in amnesia. D-amphetamine and arecoline blocked the amnestic effect of beta endorphin administered into the amygdala but it required higher doses for CCK-8, epinephrine and naloxone to block the amnestic effect of beta-endorphin. The effects of CCK-8, epinephrine and naloxone showed a differential ability to block amnesia induced by beta-endorphin intraventricularly with epinephrine and naloxone preventing amnesia but CCK-8 not improving retention. This data suggests that the memory enhancement produced by peripherally administered CCK-8 involves the amygdala and that both CCK-8 and epinephrine interact with opioid amnestic mechanisms within the amygdala to alter memory processing. PMID- 1511339 TI - Evidence of alpha-N-acetyl beta-endorphin in human cerebrospinal fluid. AB - Alpha-N-acetyl-beta-endorphin (Ac-beta-EP) is a post-translational product of beta-endorphin (beta-EP) with no analgesic properties. Ac beta-EP is present in human fetal and adult pituitary gland and cross-reacts in all available beta-EP assays. This study evaluates levels of Ac-beta-EP in the cerebrospinal fluid (CSF) of 22 normal subjects and 15 chronic headache sufferers. Since dopamine may play a role in the acetylation process, homovanillic acid levels were also determined. After extraction and high performance liquid chromatographic (HPLC) fractionation of CSF, an immunoreactive Ac-beta-EP peak was detected coeluting with reference peptide. Ac-beta-EP was detectable in all but 5 normal subjects. In headache sufferers, Ac-beta-EP levels were always detectable and their mean value was significantly higher than that of healthy subjects (11.6 +/- 11.8 vs 3.9 +/- 3.6 fmol/ml; P less than 0.01). Conversely, CSF beta-endorphin (beta-EP) concentrations were decreased in headache patients (9.8 +/- 9.4 vs 15.7 +/- 9.7 fmol/ml; P less than 0.05), and as a consequence the beta-EP/Ac-beta-EP ratio was also markedly reduced (P less than 0.005). No difference was observed for CSF homovanillic acid concentrations. These data demonstrate that HPLC coupled to radioimmunoassay allows the identification of low but significant amounts of Ac beta-EP in human CSF. This compound represents a confounding factor when beta-EP immunoreactivity is assessed by conventional methods. In headache sufferers, Ac beta-EP levels were higher than normal, whereas beta-EP concentrations were lower.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1511340 TI - Endothelin acts at the subfornical organ to influence the activity of putative vasopressin and oxytocin-secreting neurons. AB - Systemic endothelin-1 (ET-1) enhances the activity of subfornical organ (SFO) neurons with identified projections to the paraventricular nucleus of the hypothalamus (PVN). The present electrophysiological experiments were undertaken to examine the mechanisms through which systemic ET influences vasopressin secretion. Systemic ET-1 (50-100 pmol) was found to influence the excitability of antidromically identified vasopressin and oxytocin-secreting neurons in the PVN or supraoptic nucleus (SON) of urethane-anaesthetized rats. Long-term stable recordings from 95 antidromically identified neurons showed 56% of putative vasopressin- (n = 41), and 37% of putative oxytocin- (n = 54) secreting neurons were activated by ET-1. Such effects normally demonstrated a short latency (less than 10 s), with a duration ranging between 10 and 300 s. In contrast, unidentified neurons in the vicinity of PVN and SON (n = 27) were unaffected by ET-1. The inability of peptides to cross the normal blood-brain barrier suggested that such effects of ET-1 result from actions of this peptide at the SFO which lacks this barrier and sends efferent neural projections to both SON and PVN. This hypothesis was tested by obtaining similar recordings from animals in which this structure was destroyed prior to experimentation. In these studies recordings from 15 putative vasopressin- and 29 putative oxytocin-secreting neurons showed that only 7% and 14%, respectively, were excited by systemic ET-1 in lesioned animals. These data show that increases in circulating levels of ET have predominantly excitatory effects on vasopressin- and oxytocin-secreting neurons in SON and PVN. The modified responsiveness of these neurons to ET-1 in SFO-lesioned animals suggests this as a likely CNS site at which this peptide acts within the central nervous system to elicit such effects. PMID- 1511341 TI - Cholinergic and noradrenergic stimulation in the rabbit flocculus have synergistic facilitatory effects on optokinetic responses. AB - A recent study (Exp. Brain Res., 85 (1991) 475-481) showed that injection of the cholinergic agonist carbachol into the cerebellar flocculi had a pronounced facilitatory effect on the gains of the optokinetic (OKR) and vestibulo-ocular (VOR) reflexes, suggesting a positive modulatory role of the cholinergic system in the flocculus. Because many behavioral and electrophysiological studies throughout the brain have revealed a functional relationship between acetylcholine (ACh) and noradrenaline (NA), the present study was undertaken to compare the effects of floccular injection of the ACh agonist carbachol, the beta adrenergic agonist isoproterenol and the conjoint injection of both of these substances on the basic gain of the VOR and the OKR. Carbachol and isoproterenol both significantly raised the gain of the OKR, by 0.14 and 0.11 respectively. Neither of the two substances significantly affected the gain of the VOR in light or darkness. Conjoint injection of the same amounts of carbachol and isoproterenol resulted in an increase in the gain of the OKR by 0.29 without significant changes in the gains of the VOR in the light or in darkness. These results suggest a synergistic and positive modulatory role of ACh and NA in the flocculus. PMID- 1511342 TI - Increased locomotor response to novelty and propensity to intravenous amphetamine self-administration in adult offspring of stressed mothers. AB - It is suggested that drug addiction is more likely to develop in individuals who are particularly sensitive to the reinforcing effects of drugs. Animal studies of intravenous drug self-administration (SA) have shown that rats display a large range of individual differences in the propensity to develop drug-seeking. Predisposed animals are characterized by a higher locomotor reactivity to both novelty and psychostimulants. In this report, we show that prenatal stress (restraint of the mother during the last week of pregnancy) may contribute to an individual's vulnerability to develop amphetamine self-administration. The adult offspring of stressed mothers exhibited: (i) a higher locomotor response to novelty and to an injection of amphetamine (0.3 mg/kg, i.v.); (ii) a higher level of amphetamine self-administration. The data indicate that individual predisposition to drug-seeking in the adult may be induced by prenatal events. PMID- 1511343 TI - 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) reduces norepinephrine concentrations in the olfactory bulbs of male mice. AB - Male retired breeder C57/Bl and CD-1 mice were treated with either MPTP or its vehicle. At 7-10 days post-treatment, catecholamine concentrations within the olfactory bulbs (OB) and hypothalamus were determined. Norepinephrine concentrations within the OB were significantly decreased in MPTP-treated mice. These effects were more pronounced in the CD-1 (50% reduction) compared to the C57/Bl (20% reduction) strain. No effects of MPTP were observed on norepinephrine concentrations within the hypothalamus. Dopamine concentrations in the OB and hypothalamus did not differ between MPTP- and vehicle-treated mice in either strain. Overall, catecholamine concentrations within the OB, but not the hypothalamus, were significantly greater in C57/Bl compared to CD-1 mice. The reduction in OB norepinephrine concentration in the MPTP-treated animals may be related to the olfactory deficits which accompany Parkinson's disease. PMID- 1511344 TI - Differential long-term effect of AF64A on [3H]ACh synthesis and release in rat hippocampal synaptosomes. AB - The activities of various presynaptic cholinergic parameters were determined in hippocampal synaptosomes of rats 29 weeks after intracerebroventricular injection of ethylcholine aziridinium (AF64A) (3 nmol/2 microliters/side) or vehicle (saline). Synaptosomes were preloaded with [3H]choline ([3H]Ch), treated with diisopropyl fluorophosphate to inhibit cholinesterase activity and then were assayed for their content of [3H]Ch and [3H]acetylcholine ([3H]ACh) and for their ability to synthesize and release [3H]ACh. In synaptosomes from AF64A-treated rats compared with synaptosomes from vehicle-treated rats we observed that: (i) specific uptake of [3H]Ch was reduced to 60% of control; (ii) residing [3H]ACh levels were 43% of control while residing [3H]Ch levels were 72% of control; (iii) basal and K(+)-induced [3H]ACh release were 77% and 73% of control, respectively; (iv) high K(+)-induced synthesis of [3H]ACh was only 9% of control; (v) but, choline acetyltransferase activity remained relatively high, being 80% of control. These results suggest that AF64A-induced cholinergic hypofunction is expressed by both loss of some cholinergic neurons and impairment in the functioning of the spared neurons. PMID- 1511345 TI - The effects of prenatal cocaine exposure on spontaneously active midbrain dopamine neurons in adult male offspring: an electrophysiological study. AB - In this study, the technique of extracellular single unit recording was used to examine the effect of prenatal cocaine exposure on the number of spontaneously active dopamine (DA) cells in the substantia nigra pars compacta (SNC or A9) and the ventral tegmental area (VTA or A10) of male Sprague-Dawley rats on postnatal days 56-68. In addition, the effect of the direct DA receptor agonist (+/-) apomorphine (APO) on the basal firing rate of A10 DA cells was also determined. A significant decrease in the number of spontaneously active A10 DA cells was observed in offspring whose dams were treated with 40 mg/kg/day of cocaine s.c. from gestational days 8-20 when compared with offspring of pair-fed and non treated control dams. The number of spontaneously active A9 DA cells was significantly decreased in the offspring of cocaine-exposed dams when compared to pair-fed offspring. In contrast, there were no significant differences among the three prenatal groups regarding the sensitivity of spontaneously active A10 DA cells to APO (2-64 micrograms/kg, i.v.). Overall, our results suggest that in utero cocaine exposure may alter presynaptic DA activity in offspring long after their exposure has been terminated. PMID- 1511346 TI - c-fos expression in noradrenergic A2 neurons of the rat during the estrous cycle and after steroid hormone treatments. AB - The expression of the proto-oncogene product fos in noradrenergic neurons of the A2 cell group was studied with immunohistochemistry during the estrous cycle of the rat and after ovariectomy and estrogen treatments. During the estrous cycle the percentage of fos-positive norepinephrine containing neurons was highest at proestrus (39%), followed by estrus (36%) while during diestrus only 4% of the A2 neurons contained immunoreactive fos protein in their nuclei. Ovariectomy caused a further decrease in the number of fos-positive A2 neurons (2%) while long-term estradiol administration partially reversed the effects of ovarian steroid removal (19%). However, 3 h after a single subcutaneous injection of estradiol into ovariectomised rats, 79% of the noradrenergic neurons in the A2 area showed fos immunoreactivity in their nuclei. The results indicate that fos-expression in the noradrenergic neurons in the A2 region varies depending upon the circulating estradiol levels. Since norepinephrine stimulates gonadotropin releasing hormone (GnRH) secretion from the median eminence during proestrus and the GnRH neurons do not contain estrogen receptors, it is suggested that the A2 region is, at least in part, responsible for conveying the estrogen signal to the GnRH neurons. PMID- 1511347 TI - Zebrin II distinguishes the ampullary organ receptive map from the tuberous organ receptive maps during development in the teleost electrosensory lateral line lobe. AB - In weakly electric gymnotiform teleosts, monoclonal antibody anti-zebrin II recognizes developing pyramidal cells in the ampullary organ-receptive medial segment of the medullary electrosensory lateral line lobe (ELL) and in the mechanoreceptive nucleus medialis. Developing pyramidal cells in the remaining three tuberous organ-receptive lateral ELL segments are unreactive. These results suggest that certain biochemical features of the ELL ampullary organ-receptive medial segment are more similar to the nucleus medialis than to the tuberous organ-receptive ELL segments, and support the hypothesis that the ampullary system evolved from mechanosensory precursors. PMID- 1511348 TI - A role for acetylcholine in conditioning-related responses of rat frontal cortex neurons: microiontophoretic evidence. AB - In an associative conditioning paradigm, an auditory stimulus (CS+) was paired with rewarding medial forebrain bundle stimulation or a tone of different frequency (CS-) was presented without pairing. After training, slow potential (SP) and single neuron responses were recorded from rat frontal cortex. When cortical SP responses indicated the development of discrimination between CS+ and CS- tones, single neurons could be isolated that exhibited a discriminative response to CS+. Seventy-three percent of the 56 neurons which discriminated between CS+ and CS- were excited by the paired tone while the remainder were inhibited. Iontophoretically applied acetylcholine increased spontaneous firing rate in 90% of the excited cells and 87% of the inhibited cells. Iontophoretic administration of a muscarinic receptor antagonist, either atropine or tropicamide, during trial presentation attenuated the conditioning-related response to CS+ as well as the response to acetylcholine in the majority of neurons. The largest group of discriminating neurons were excited by both CS+ and acetylcholine, and both responses were suppressed by the antagonists. The results provide evidence that conditioning-related responses of a major population of frontal cortex neurons are modulated by cholinergic input, a portion of which may originate in the basal forebrain area. There also may be a significant non cholinergic influence on these neuronal responses. PMID- 1511349 TI - Nerve growth factor promotes collateral sprouting of cholinergic fibers in the septohippocampal cholinergic system of aged rats with fimbria transection. AB - Nerve growth factor (NGF) was injected intraventricularly into aged (24 months) rats with unilateral fimbria transection. Controls received intraventricular injections of cytochrome c. A quantitative analysis of acetylcholinesterase (AChE)-positive fibers was used to evaluate whether the NGF treatment can stimulate regeneration and reinnervation of the cholinergic axons in the septohippocampal system of aged rats with fimbria transection. A marked increase in the density of AChE-positive fibers was observed in the lateral septum, the dorsal fornix and the dorsal hippocampus of the NGF-treated animals, as compared to the controls. In the lateral septum, the increase was observed in the 2-month NGF-treated animals but not in the 15-day NGF-treated animals. In the dorsal fornix at the level of the dorsal hippocampus, the increase was observed on both the lesioned and unlesioned sides of both the 15-day and 2-month NGF-treated animals. In the denervated (lesioned side) hippocampus, the increase took place in the dorsal hippocampus but not in the ventral hippocampus of both the 15-day and 2-month NGF-treated animals. There was no recovery of AChE-positive fibers on the lesioned side of the fimbria distal to the lesion site even in the 2-month NGF-treated animals. These results demonstrate that intraventricular injections of NGF can stimulate collateral sprouting of intact cholinergic axons in the septohippocampal system and promote cholinergic reinnervation of the denervated hippocampus of aged rats with fimbria transection. PMID- 1511350 TI - Regional differences in brain norepinephrine and dopamine uptake kinetics in inbred rat strains with hypertension and/or hyperactivity. AB - High-affinity uptake of norepinephrine (NE) and dopamine (DA) were determined in synaptosomes of brain regions from four genetically related inbred rat strains, all derived from the Wistar-Kyoto rat: SHR, WKY, WKHA and WKHT strains. SHRs express hypertension and hyperactivity, WKHAs express hyperactivity alone, WKHTs express hypertension alone, and WKYs are neither hypertensive nor hyperactive. Significant increases in NE uptake, primarily in Vmax, in cerebral cortical areas and the cerebellum, were associated with the hypertensive trait. Significant increases in DA uptake Vmax in the frontal cortex were associated with the inheritance of hyperactivity among these strains. A limited study in SHRs indicated that DA uptake in the frontal cortex increased with age, and that males did not differ from females. No changes in DA uptake in the neostriatum were found with respect to either strain, or age or sex. These findings revealed changes in brain catecholamine neuronal function that are of relevance to both hypertension and hyperactivity. This was made possible by the availability of WKHA and WKHT, in addition to WKYs, as appropriate controls for the SHR. PMID- 1511351 TI - Polyamines inhibit N-methyl-D-aspartate antagonist-induced darting behavior in the rat prefrontal cortex. AB - The competitive NMDA (N-methyl-D-aspartate) receptor antagonist, CPP (3(2 carboxypiperazin-4-yl)-propyl-1-phosphonic acid), microinjected into the medial prefrontal cortex of rats, induces a unique behavioral syndrome termed 'darting', characterized by rapid leaping across an open field arena. In addition, CPP induces generalized hyperactivity when microinjected into the medial prefrontal cortex, nucleus accumbens, and caudate nucleus. Polyamine modulation of the NMDA receptor was tested at the medial prefrontal cortex microinjection site in this behavioral paradigm. The polyamine spermidine, and its diamine precursor, putrescine, blocked CPP-induced darting behavior, as well as CPP-induced hyperactivity, at doses which did not decrease locomotor activity when administered alone. The putative polyamine antagonists, ifenprodil and diethylenetriamine, did not prevent spermidine from inhibiting CPP-induced darting. These results suggest that polyamines, presumably by acting as positive allosteric modulators of the NMDA receptor, can inhibit the CPP-induced behavioral syndrome at the prefrontal cortex site. PMID- 1511352 TI - Neurons in the median preoptic nucleus of the rat with collateral branches to the subfornical organ and supraoptic nucleus. AB - A novel pathway between the subfornical organ and the supraoptic nucleus involving the collateral branches of cell bodies situated in the lamina terminalis has been studied. Fluorogold was injected into the supraoptic nucleus and rhodamine-labelled microspheres into the subfornical organ of rats. Nineteen % of neurons in the median preoptic nucleus and 30% of neurons in the OVLT projecting to the subfornical organ also had axons extending to the supraoptic nucleus. These pathways may represent a novel trajectory for the rely of information from the lamina terminalis to the supraoptic nucleus. PMID- 1511353 TI - Handpiece sterilization. PMID- 1511354 TI - Handpiece sterilization. PMID- 1511355 TI - Handpiece sterilization. PMID- 1511357 TI - CDAnet. PMID- 1511356 TI - Handpiece sterilization. PMID- 1511358 TI - Teamwork. PMID- 1511359 TI - Canada is not for sale. PMID- 1511361 TI - Implant dentistry. A conversation with George Zarb. PMID- 1511360 TI - Make mine modular: an update on computer technology. PMID- 1511362 TI - Surgical correction for esthetic problems associated with dental implants. PMID- 1511363 TI - Osseointegrated implants for stabilization of the partially edentulous patient. PMID- 1511364 TI - Titanium--the metal of the gods. PMID- 1511365 TI - Prosthodontic rehabilitation of a patient with mucormycosis. PMID- 1511366 TI - Treatment of anterior cross-bites in the early mixed dentition. AB - The diagnosis and treatment of anterior cross-bites are described by categorizing anterior cross-bites into three groups. Appropriate appliance therapy is described in sufficient detail to enable the general dental practitioner to provide interventional treatment. PMID- 1511367 TI - Dental anxiety: differentiation, identification and behavioral management. AB - Dental anxiety has always been and still is a major impediment to regular dental care for a significant proportion of the general public. In years past, dental professionals could afford, by and large, to ignore this problem. Practices could flourish based on their technical virtuosity, and fearful or anxious patients might be considered a burden rather than a concern. Today, however, the laws of supply and demand are causing dentists to pay increased attention to aspects of the profession that extend beyond the science of clinical technique. A successful practice now depends on interpersonal as well as technical skills, particularly the ability to manage dental anxiety. Despite this, most dentists admit to a surprising lack of confidence when it comes to understanding the nature of anxiety and the modern methods advocated for its everyday management, which generally rely on behavioral modes of intervention. This paper is designed to familiarize practitioners with some of the basic elements of dental fear and anxiety, and their day to day management. PMID- 1511368 TI - Colon cancer overview. AB - The scope of current prevention research support by the National Cancer Institute includes the clinical assessment of dietary modifications and cancer screening trials, epidemiologic studies, development of new chemopreventive therapies, and the use of advanced molecular biologic technologies to probe the genetic determinants of colorectal adenomas. Colorectal cancer frequently has been associated with high-fat low-fiber diets in epidemiologic and experimental studies. A recently initiated Phase III Dietary Intervention Study of Recurrence of Large Bowel Adenomatous Polyps will investigate the potential benefits of a low-fat high-fiber fruit-and-vegetable-enriched eating pattern to decrease the polyp recurrence rate. The Chemoprevention Program currently is supporting four Phase III controlled clinical intervention trials investigating the cancer inhibiting effects on colorectal cancer of beta-carotene, piroxicam, calcium, and calcium plus fiber in persons with previous adenomas. A proposed early detection trial will screen for colorectal, prostate, lung, and ovarian cancers. A comparison of incidence and mortality trends indicates progress in colorectal cancer detection and therapy. PMID- 1511369 TI - Molecular genetics of colorectal carcinoma. AB - The molecular genetics of colorectal carcinoma are among the best understood of any common human cancer. Reported molecular genetic abnormalities involve tumor suppressor genes that undergo inactivation (e.g., apc, mcc, dcc, p53, and possibly genes on chromosomes 8p, 1p, and 22q) and dominant-acting oncogenes (e.g., ras, src, and myc). Multiple clonal genetic abnormalities accumulate during the development of colorectal carcinoma in adenomas. Altered DNA methylation is an early event, and the specific genetic alterations occur in a preferential order. However, the clinical application of molecular genetics in patients who are at risk for or have colorectal carcinoma is in its infancy. Patients with a predisposition to colorectal carcinoma caused by inheritance of familial adenomatous polyposis can be identified by genetic analysis of the apc gene on chromosome 5q21. In patients who undergo curative resection of colorectal cancer, deletion of the p53 gene on chromosome 17p, deletion of the dcc gene on 18q, and high fractional allelic loss (fraction of nonacrocentric autosomal arms with deletion) in the primary tumor appear to indicate an increased likelihood of occult disseminated disease and thus a poor prognosis. Additional studies are needed to establish the role of the molecular genetics of colorectal carcinoma in the management of patients who are at risk for or already have neoplasia of the large bowel. PMID- 1511371 TI - Screening and early diagnosis. AB - Although colorectal cancer is the second leading cause of death in the US, the majority of diagnoses are made at an advanced stage, and screening detects 70% at an early stage, controversy has existed because of a lack of experimental controlled trial evidence showing a decrease in mortality. Indirect and now direct evidence supports the current screening guidelines of the American Cancer Society and the National Cancer Institute as reasonable and should be continued. PMID- 1511370 TI - The National Polyp Study. Design, methods, and characteristics of patients with newly diagnosed polyps. The National Polyp Study Workgroup. AB - The National Polyp Study (NPS) is a multicenter prospective randomized trial designed to evaluate follow-up surveillance strategies in patients who have undergone polypectomy for the control of large bowel cancer. The study design was developed by a joint research committee from American Gastroenterological Association, the American Society for Gastrointestinal Endoscopy, and the American College of Gastroenterology. Subjects who met the eligibility criteria were randomized into two different treatment arms. Eligibility criteria included: removal of one or more adenomas; complete colonoscopy; no prior polypectomy, inflammatory bowel disease, or familial polyposis; and no history of colon cancer. The treatment arms consisted of a frequent follow-up (1 and 3 years after initial polypectomy) and a less frequent follow-up (3 years). Follow-up examinations included fecal occult blood tests, air-contrast barium enema, and colonoscopy. The latter was done on 9112 referred patients at the seven participating centers from November 1980 until February 1990 who had no history of polypectomy, colon cancer, familial polyposis, or inflammatory bowel disease. Of these patients, 4763 (52.3%) had no polyps; 549 (6.0%) had an invasive cancer; 776 (8.5%) had nonadenomatous polyps; 208 (2.3%) had incomplete examinations; 184 (2.0%) had other findings; and 2632 (28.9%) had one or more adenomas, of which 1418 (53.9%) were randomized to one of the two treatment arms. This article reports the background, rationale, objectives, methods, and organization of this study and includes patient characteristics on initial presentation. Future data provided by the NPS may help in the development of recommendations for surveillance guidelines for such patients. This study also provides a framework to address questions regarding the natural history of adenomas and their relationship with colorectal cancer. PMID- 1511372 TI - Goals of screening. AB - BACKGROUND: Colorectal cancer is a major target of inquiry into the effectiveness of screening in the control of the disease by earlier detection and possibly reduced incidence after removal of polyps. Four randomized clinical trials are in process to determine the efficacy of fecal occult blood tests (FOBT) in reducing mortality from colorectal cancer. METHODS: General issues that affect decisions to initiate screening, benefits and risks, and precision of screening are discussed. Trends in incidence, mortality, stage at detection, and survival are reviewed. RESULTS: Colorectal cancer retains a relatively high incidence and mortality; improvements are occurring in stage of detection and survival. Definitive results from randomized clinical trials on efficacy of screening with FOBT are not yet available. CONCLUSIONS: Guidelines for colorectal screening of asymptomatic subjects in the general population have been adopted by the American Cancer Society and the National Cancer Institute. Other organizations have concluded there is insufficient evidence to recommend for or against FOBT. PMID- 1511373 TI - Occult blood screening. Obstacles to effectiveness. PMID- 1511374 TI - Flexible sigmoidoscopy and the despecialization of gastrointestinal endoscopy. An environmental impact report. AB - BACKGROUND: Gastrointestinal endoscopy is a diagnostic and therapeutic tool for the prevention of premature death from cancer. Flexible equipment innovations during the 1970s increased the power of this technique dramatically. For family physicians and general internists, dissemination of these techniques started around 1979 and continued during the 1980s. METHODS: In this report, data describing the gradual reformation of primary-care cancer screening are discussed. RESULTS: For example, one longitudinal study revealed a sustained improvement in physician compliance with American Cancer Society guidelines associated with the advent of flexible sigmoidoscopy and short colonoscopy skills. For symptomatic patients, compliance increased from 2% to 79% over 5 years. CONCLUSIONS: Flexible sigmoidoscopy is now well accepted. Endoscopic biopsy, full colonoscopy, and polypectomy skills are now available to many primary-care physicians. This represents a technical advance, and it is a small part of a larger medical-care revolution in which technology is decentralized. This holds great promise for the eradication of premature death from colorectal cancer. PMID- 1511375 TI - The role of the barium enema in the detection of colonic neoplasms. AB - The variability in the published results for colonoscopy and barium enema examinations is confusing. With both, optimum studies depend on meticulous preparation, technical excellence, and operator proficiency. The equivalency of results and the lower cost of the radiologic study indicate that the double contrast barium enema is the technique of choice for the examination of asymptomatic patients or symptomatic individuals without known antecedent disease. The relatively small difference between the cost of the double-contrast enema examination and sigmoidoscopy ($193 versus $135) suggests that it should replace the latter on the 3-5-year screening schedule because, on average, 50% more of the colon is examined by the barium study. It is a mistake to place colonoscopy and barium enema in competitive positions; the two methods ideally complement one another. The exclusion of significant pathologic findings by the double-contrast enema can be accepted, but the detection of abnormalities should be followed, when necessary, by colonoscopic verification and/or biopsy. The number of times both will be required are few. Radiologically demonstrated colon carcinomas seldom require biopsy verification, and 90% of all polyps are smaller than 5 mm in diameter with a negligible incidence of malignant transformation. When the examinations are used in the proper sequence, they provide a cost effective approach to the early detection and control of cancer of the large bowel. PMID- 1511376 TI - Hereditary aspects of colorectal adenomas. AB - BACKGROUND: Inheritance is important to the development of colonic adenomatous polyps and colon cancer. Current knowledge of inherited susceptibility to colonic neoplasms suggests that colon cancer screening strategies should consider familial and genetic risk. METHODS: This report reviews the literature pertinent to adenomatous polyp and colon cancer inheritance and suggests polyp-cancer screening procedures based on inherited or familial risk. RESULTS: Colorectal adenomas and cancer occur in several rare inherited syndromes and more commonly as sporadic cases. Intensive screening protocols have been suggested for the inherited syndromes because of the high associated cancer risk. Recent evidence suggests that inherited susceptibility also may be important in a large fraction of the so-called sporadic cases. Preliminary screening guidelines are suggested for this category based on the number of first-degree relatives affected with colon cancer. CONCLUSIONS: Inherited susceptibility appears to be more important to the pathogenesis of colorectal adenomas and cancer than previously recognized. Screening strategies which consider inherited risk may increase the effectiveness of cancer detection and prevention. PMID- 1511377 TI - Colon cancer genetics. AB - The terms "hereditary," "sporadic," and "familial" colorectal cancer (CRC) suggest a knowledge of causation; however, current understanding of CRC does not permit categorization of differing CRC risks in accord with their cause per se. Despite these serious shortcomings, these terms are defined operationally on the basis of a family history of cancer, and when available, additional phenotypic information. The sporadic type occurs in the absence of a family history of CRC in a first-degree relative. The familial type occurs when at least one first degree relative has CRC. Both these categories require the exclusion of hereditary CRC. In the case of hereditary CRC, this type is defined as a family history of CRC occurring in a pattern that indicates autosomal-dominant inheritance, which also may involve certain phenotypic signs (depending on the specific disorder, i.e., florid adenomatous polyps, benign and malignant extracolonic lesions, cancer of unusually early onset, and multiple primary cancer, particularly synchronous and metachronous CRC). Although this operational classification does not produce etiologically homogeneous groups, it is believed to have pragmatic utility with respect to planning targeted surveillance and management strategies. Because of the distinctive natural history of CRC in hereditary syndromes, it is of paramount clinical importance to identify hereditary CRC when it does occur. Even in patients with no evidence of hereditary CRC syndrome, their family history may be second only to age in determining the best CRC screening program for those who are asymptomatic. In an attempt to provide a perspective on the clinical evaluation of CRC risk, research was reviewed on pathologic features and biomarkers that may be related to CRC causes, especially the genetic basis of CRC susceptibility. The long-term objective of studies on the genetic epidemiology of CRC is primary and secondary prevention through development of targeted management and surveillance recommendations (based on an understanding of CRC causation) that is relevant to hereditary, familial, and sporadic CRC. PMID- 1511378 TI - Inflammatory bowel disease and colon cancer. AB - Patients who have had extensive colitis for more than 10 years are at increased risk for colorectal cancer. The risk may be greatest for those whose onset of illness is in childhood. Management options for patients at increased risk include prophylactic colectomy or endoscopic surveillance. The object of surveillance is prevention of cancer by detecting premalignant lesions that predispose to cancer. A less desirable objective is the diagnosis of cancer at an early curable stage. Patients must be well informed about their risk for cancer, the limitations of endoscopic surveillance, and the availability of surgical alternatives. Current endoscopic and pathologic techniques focus on the detection of dysplasia, but newer biomarkers may offer greater sensitivity and specificity in the future. PMID- 1511379 TI - Precursors of colorectal carcinoma. Biopsy and biologic markers. AB - The term biologic marker (biomarker) of colorectal cancer refers in this article to an early preclinical phenotypic characteristic that relates to the risk for developing this cancer. Putative biologic markers in the normal colorectal mucosa of patients at risk include abnormal cell proliferation as determined by kinetic studies, ornithine decarboxylase activity, and polyamine synthesis. Alterations of mucin synthesis have been studied using both histochemical stains and lectin binding techniques. Blood group and related carbohydrate antigens also have been evaluated as potential biomarkers in the normal mucosa. Biopsy small (less than 5 mm) polyps encountered at endoscopy has become a standard practice. Although a small polyp found to be an adenoma has a low likelihood of harboring high-grade dysplasia or invasive carcinoma, it represents an indicator of risk for colorectal neoplasia. Hyperplastic polyps, however, even though they have certain epidemiologic associations with colorectal neoplasia, are controversial as putative biomarkers of clinical relevance. Current research supports a concept of a field defect of the colorectal mucosa at risk for neoplasia, which may be identified by phenotypic abnormalities of the normal mucosa and the development of small adenomas. PMID- 1511380 TI - Preoperative evaluation of patients with primary colorectal cancer. AB - Preoperative evaluation should focus on techniques that either preclude surgery entirely, alter the planned operation either preoperatively or intraoperatively, or suggest the need for preoperative adjuvant therapy. The presence of a synchronous colonic neoplasia should be excluded by colonoscopy or air-contrast barium enema combined with sigmoidoscopy. A preoperative carcinoembryonic antigen level provides useful prognostic information. Abdominal computed tomography (CT) or hepatic ultrasonography should be done in patients with hepatomegaly or abdominal liver function tests. Those with rectal cancer should undergo a careful digital palpation done by an experienced observer combined with rigid proctosigmoidoscopy. Intrarectal ultrasonography may provide more objective data in regard to the extent of the local disease. If preoperative radiation therapy is planned, abdominal CT is appropriate to exclude extrapelvic disease that would preclude such a strategy. The benefit of routine preoperative CT in patients with otherwise resectable colonic or rectal cancer remains unclear. PMID- 1511381 TI - Preoperative evaluation. Medical obstacles to surgery. AB - The primary curative therapy for colorectal cancer is surgical resection. In addition, surgery is the mainstay for palliative therapy in most patients with more advanced colorectal cancer. Medical problems may have an impact on the decisions of when to operate and what procedure to do. Postoperative morbidity and mortality are affected by preoperative medical conditions. These medical problems may be secondary to the carcinoma, such as obstruction, perforation with sepsis, or malnutrition, or may be a result of underlying disorders, especially cardiopulmonary diseases. Adequate evaluation and indicated therapeutic intervention before surgical procedures will improve the patient's outcome. PMID- 1511382 TI - Treatment options for the patient with colorectal cancer. AB - Treatment decisions for patients with colorectal cancer depend on the site and extent of the cancer. Medical factors rarely preclude appropriate treatment. For colonic and upper rectal cancer, curative treatment is almost entirely operative. Even patients with disseminated colon cancer merit a limited palliative resection to abort bleeding and prevent obstruction. When surgery is elective, colostomy is rarely necessary, although it may be required in patients who have obstructed or perforated colon cancer. For distal rectal cancer, various treatment options, including radiation therapy, have reduced the need for a colostomy, although maintaining comparable cure rates. Currently, only about one in seven patients with rectal cancer requires a permanent colostomy. PMID- 1511383 TI - Perioperative teaching and counseling. AB - BACKGROUND: Patients who undergo surgery for colorectal cancer resulting in an abdominal stoma need extensive teaching and counseling to fully recover and enjoy a satisfactory quality of life. METHODS: The economics of health care, changes in length of hospital stay, what and how patients are taught, and ways in which adults learn were reviewed. Each of these influences on acquisition of self-care skills and knowledge were considered as they apply to the specific needs of stoma patients. RESULTS: Common misconceptions about ostomies should be dispelled to clear the way for adults to learn what they need to know to care for their ostomy. Postoperative teaching must wait until patients are alert and comfortable enough to attend to instruction. Educational material should be prepared at the patient's level of understanding. CONCLUSIONS: An adequate budget for education and dedicated patient education personnel are necessary for effective perioperative teaching and counseling of ostomy patients. In today's health-care system, patients who require a stoma need access to outpatient preoperative and postoperative training and emotional support. PMID- 1511384 TI - Operative treatment of colorectal cancer. AB - Principles of radical surgery for curative treatment of colon and rectal cancer are based on 5-year survival and 2-year local recurrence rates. Depth of invasion, cellular differentiation, vascular invasion, and the location and number of lymph node metastasis influence the 5-year survival rate. Age, type of resection, obstruction or perforation of the primary tumor, and the surgeon's technique influence the 2-year local recurrence rate. Accordingly, high ligation of major vascular pedicle, tumor-free margins, resection of contiguous organs, and oophorectomy should improve survival and an additional benefit may be derived from complete excision of distal mesorectum and the "no-touch isolation technique." PMID- 1511385 TI - Conservative treatment of rectal cancer. Extending the indications. AB - Rectal cancer often in the past was believed to require abdominoperineal resection with permanent colostomy to achieve a cure. Several surgical alternatives to colostomy currently are available for selected patients. Understanding of the methods of preoperative staging is increasing, and new techniques, such as intrarectal ultrasound, have provided improved accuracy. By applying this and other methods of preoperative staging, selection of a surgical approach appropriate to the tumor stage increasingly is possible. Curative treatment for rectal cancer often can be achieved while preserving anorectal function. PMID- 1511386 TI - Accomplishments in surgical adjuvant therapy for large bowel cancer. AB - In the past, effective surgical adjuvant therapy has been an elusive goal with little or no evidence of benefit from chemotherapy, immunotherapy, or radiation therapy. During the last 2 years, however, randomized trials have produced strong evidence of substantive progress. In colon cancer with regional nodal metastasis, therapy with combined 5-fluorouracil (5-FU) and levamisole has resulted in a 41% reduction in the recurrence rate (P less than 0.00005) and a 33% reduction in the death rate (P = 0.0052). In rectal cancer, combined technique adjuvant therapy using radiation (50.4 Gy) given in combination with 5-FU and preceded and followed by full-dose systemic chemotherapy with a 5-FU-based regimen was evaluated. In comparison with the same dose of radiation used alone, this combined regimen reduced the recurrence rate by 33% (P = 0.0016) and the death rate by 29% (P = 0.025). Of almost equal importance, there was a major reduction in local recurrence from 25% to 13%. Both these regimens would seem sufficiently well established to justify offering them as standard treatment. Of greater potential value to the patient, however, is entry into the currently available clinical trials that are pursuing hopeful avenues of research and offer the prospect of still greater accomplishments in the years to come. PMID- 1511387 TI - Adjuvant radiation therapy for colorectal cancer. AB - BACKGROUND: Despite apparently complete resection of cancers of the rectum or colon, many patients have recurrences in the area from which their primary cancer was excised and in more distant organs. Radiation therapy has been used either alone or in combination with chemotherapy as an adjuvant to surgery to reduce the risk of recurrence. METHODS: The literature describing the results of adjuvant radiation treatment for colorectal cancer was reviewed. RESULTS: In randomized studies in patients with moderately advanced rectal cancers (T2-4 N0, M0 or N1-3, M0) adjuvant radiation therapy has often reduced the risk of pelvic recurrence, but has had little effect on survival rates or the risk of extrapelvic metastases. Recent reports show that combined radiation and chemotherapy can improve both disease-free survival and survival rates. Such treatment has caused only moderate toxicity in most studies. Nonrandomized studies in patients in whom small superficial rectal cancers are treated by local excision suggest that adjuvant radiation therapy reduces the risk of pelvic recurrence after this limited surgery and allows anorectal function to be preserved. Strategies similar to those developed for the treatment of rectal cancer are being studied in patients with colon cancer. CONCLUSIONS: In moderately advanced rectal cancers, the combination of chemotherapy and radiation is more effective than radiation alone in reducing local recurrence and increasing survival rates. Additional trials are needed to improve results and to refine drug and radiation schedules. Radiation alone may be sufficient as an adjuvant treatment when combined with local excision of small rectal cancers. The role of radiation in the adjuvant treatment of colon cancer is investigational. There is a need to more accurately delineate the patients with colorectal cancer most likely to benefit from adjuvant therapy. PMID- 1511388 TI - Anal cancers. Squamous and melanoma. AB - The total experience at Memorial Sloan-Kettering Cancer Center with two types of anal cancers--squamous and malignant melanoma--is reviewed. The squamous type is much more common, and its anatomic distinction between that of the anal margin and the anal canal is important in its respective clinical and surgical management. The historical, purely surgical management of canal lesions has evolved into the current chemoirradiation management, followed by the surgical approach with improvement of the 5-year survival rate and salvage of rectums. Malignant melanoma, which is the much rarer anal cancer, is still occasionally salvageable, with the use of standard abdominoperineal resection. PMID- 1511389 TI - Role of the enterostomal therapy nurse in ostomy patient rehabilitation. AB - Enterostomal therapy (ET) nurses specialize in the management of patients with urinary and fecal diversions, draining wounds and fistulas, fecal and urinary incontinence, and chronic wounds such as pressure ulcers and vascular ulcers. ET nurses have much to offer in the management of patients with cancer. Such nurses play a major role in the rehabilitation of patients undergoing fecal or urinary diversions. Preoperative services include: counseling regarding planned surgical procedure, the impact of an ostomy on the patient's life, and the basics of ostomy management; sexual counseling; and stoma site selection. Postoperatively, the ET nurse instructs the patient and family in ostomy care, dietary and fluid alterations, and ways to incorporate ostomy management into the patient's life. The ET nurse also provides long-term follow-up care in outpatient settings; such care includes ongoing counseling, education, and surveillance for complications requiring medical intervention. ET nurses can recommend appropriate measures to prevent and manage skin breakdown that is related to immobility, friable skin, incontinence, and/or radiation therapy. They also can assist in correcting or containing fecal or urinary incontinence and in cost-effective management of draining wounds and fistulas. PMID- 1511390 TI - Staging of cancer of the colon and rectum. PMID- 1511391 TI - Colorectal cancer. Principles of postoperative follow-up. AB - Monitoring patients after primary large bowel surgery for malignancy is predicated on the concept that early detection of recurrence may provide salvage treatment for cure. Knowledge of the pathologic site and stage provides important information as to the probability of recurrence and the patterns of failure that are likely to occur. Available methods to detect recurrence include clinical, roentgenographic, and serum tests that are done more frequently during the first 2 years after surgery. Monitoring plasma carcinoembryonic antigen levels can lead to identification of asymptomatic recurrences, but there is controversy about the curability of recurrences outside the liver. Newer techniques (such as computed tomographic portography, intraoperative ultrasonography, and radioimmunoguided surgery) provide greater diagnostic accuracy and lead to more appropriate procedures during "second-look" operations. For example, hepatic resection in properly selected patients offers up to a 30% chance of cure and should be pursued aggressively. A search for metachronous cancers by endoscopy also should be done. Knowledge of the potential and patterns of failure can provide a useful guide during the postoperative follow-up care of the patient with large bowel cancer. PMID- 1511392 TI - Patterns of recurrent colorectal cancer and recovery surgery. AB - In only two areas of colorectal cancer recurrence does surgery provide benefit. For a minority of patients with liver metastases that can be resected completely, cure is possible. Recent data from a prospective liver surgery protocol provide a perspective on the outcome, morbidity, and mortality of the procedure and confirm many of the suggestions in previous retrospective reviews. For patients with isolated pelvic or perineal recurrence, surgical removal of recurrent tumor provides palliation, but only if in-hospital convalescence is minimal and if recently introduced reconstructive techniques allow early rehabilitation. PMID- 1511393 TI - Chemotherapy for metastatic colorectal cancer. AB - The systemic management of patients with colorectal cancer continues to focus on the use of 5-fluorouracil (5-FU). In the setting of metastatic disease, parenteral 5-FU has been shown to be superior to oral 5-FU; however, survival duration seems similar whether such parenteral 5-FU is administered in a "loading," weekly, or continuous infusion manner. The addition of other cytotoxic agents such as semustine, mitomycin C, or cisplatin to 5-FU does not appear to increase the response rate or prolong survival. The results of five randomized trials assessing the value of intraarterial hepatic infusions of 5-FU or floxuridine show that such regional chemotherapy increases the likelihood of hepatic response compared with systemic treatment but has little effect on survival and is associated with significant toxicity. Recent efforts in the management of patients with advanced disease have been directed at optimizing the activity of 5-FU by (1) enhancing the inhibition of DNA synthesis through the concomitant administration of folinic acid; (2) increasing drug incorporation into RNA through pretreatment with methotrexate or phosphonacetyl-L-aspartate; and (3) improving the drug's activity through the synergistic action of alpha-2a interferon. Although the results of some of these investigations have been promising, only the 5-FU and folinic acid combination consistently has appeared to be superior to single-agent 5-FU. These different approaches to biochemical modulation are being compared in ongoing cooperative group trials. PMID- 1511394 TI - Immunotherapy of colorectal cancer. AB - Specific and nonspecific stimulation of the host immune system to reject cancer is an attractive concept that is just beginning to mature. Results with crude extracts and nonspecific immune stimulation have been variable. However, the recent observations of improved survival after administration of levamisole plus 5-fluorouracil in the adjuvant setting have made an impact on the treatment of colorectal cancer. Animal studies consistently show that immune therapies are most effective for disease that is not advanced. Thus, the small benefit seen with levamisole, a low toxicity immunomodulator, suggests that much more impressive results can be anticipated with more potent and specific agents. Postsurgical autologous tumor cell vaccine has been effective in some prospective randomized trials; in others, no benefit was found. The identification and purification of allogeneic tumor-associated antigens has lead to enhanced antigen specific host cell-mediated immunity; this may result in more consistent antitumor effects. The current development of chemically defined immune adjuvants of low toxicity allows tumor-specific immune stimulation to be tested in high risk apparently healthy patients after resection of colorectal cancer (Stages II and III). The influx of information regarding immune cell populations, cell surface markers, and cytokines has fostered extensive exploration of lymphocyte stimulation, in vitro cell growth and expansion, and in vivo evaluation in patients with advanced cancer. Modest tumor response rates have been documented with adoptive transfer of lymphokine-activated killer cells and interleukin-2. Improved results are anticipated with the more potent tumor-infiltrating lymphocytes and specific in vitro sensitization of draining lymph node cells to autologous and allogeneic tumor antigens. Murine monoclonal antibodies specific for cell-surface markers, such as carcinoembryonic antigen, have been tested for their value in the diagnosis and therapy of colorectal cancer. A small response rate has been seen with single and multiple injections of C017-1A, a monoclonal antibody specific for colonic and pancreatic cancer. The development of antiidiotypic antibodies in these patients may have been important in those that responded to this type of therapy. However, laboratory evidence suggests that monoclonal antibody conjugated to a cytotoxic agent (i.e., radionuclide, drug, or toxin) should be much more effective. Radioimmunotherapy trials in the nude mouse model bearing human colon cancer xenografts showed good tumor incorporation of the radionuclide (yttrium 90 or iodine 131), inhibition of tumor growth, and long term survival.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1511395 TI - Radiation therapy for advanced colorectal cancer. AB - Locally advanced, inoperable, and recurrent colorectal cancer requires multitechnique therapy to achieve optimal control and palliation. The role of radiation therapy as an adjuvant in resectable rectal cancer has been studied extensively in clinical trials, but its role in more advanced disease has not been explored to the same extent. The use of radiation in colonic rather than rectal cancer is more problematic because of natural tissue tolerance constraints in the abdomen versus the pelvis. The current and past role of radiation in advanced colorectal cancer will be reviewed, and avenues of ongoing and future investigation will be outlined. The role of radiation for palliation also will be discussed. PMID- 1511396 TI - Health quality of life and colorectal cancer. AB - BACKGROUND: Quality of life associated with cancer and radiation treatment includes the dimensions of psychologic and physical well-being, nutrition concerns/side effects, and radiation treatment-related anxiety/adjustment. An understanding of the impact of colorectal cancer and radiation treatment on these aspects of health quality of life can be reached by comparing this diagnostic group to others undergoing similar treatment. METHODS: Thirty-six patients with colorectal cancers, 41 with uterocervical cancers, 43 with genitourinary tumors, 13 with leukemia or bone metastasis, and 129 with head and neck cancers undergoing radiation therapy provided complete health quality of life index (QLI RT) data during weeks 1 and 3 of treatment and at the first follow-up visit after treatment completion. The QLI-RT was found to be reliable and valid. RESULTS: Those with colorectal cancer had similar QLI-RT summary scores as the other groups at the beginning of treatment and during the follow-up period. QLI-RT scores tended to range from 62 to 84 for the summary score and individual-item scores; this was a narrow span considering the QLI-RT uses a 0-100-mm linear analog-response scale. The exceptions were strength, which elicited scores in the 46-68 range and a couple of responses to worrying about radiation therapy. The largest change in QLI-RT score in relation to the treatment trajectory was 11 mm. CONCLUSIONS: These findings tend to support the notion that patients with cancer try to maintain health quality of life at an acceptable level despite the occurrence of stressful negative events. Future research should explore the stable versus dynamic attributes of health quality of life to learn more about the factors that contribute to the adaptive process that maintains such quality of life at an acceptable level. PMID- 1511397 TI - Interactive display of volumetric data by Fast Fourier Projection. AB - This article describes a new algorithm for reprojection of volumetric data, called Fast Fourier Projection (FFP), which is one to two orders of magnitude faster than conventional methods such as ray casting. The theoretical basis of the new method is developed in a unified mathematical framework encompassing slice imaging and conventional volumetric reprojection methods. Software implementation is discussed in detail. The article closes with an account of experience with a prototype FFP implementation, and applications of the technique in medical visualization. PMID- 1511398 TI - Correction of aberration in image-intensifier systems. AB - A mathematical model describing spatial distortions caused by an image intensifier has been developed. These distortions originate from projecting a flat plane onto a curved input phosphor surface. Considering the source of these distortions and their magnification along the radial distance, it is possible to describe them in terms of the geometrical relations between a point on a physical object and its projection onto an input phosphor screen's spherical surface. On the basis of these relations, the correction of pixel coordinates and pixel values has been performed. Parameters included in the derived formula consider the radius of curvature of the input screen, the view angle, the distance from the focal spot to the object, and the distance from the focal spot to the input phosphor screen. These parameters make the correction formula system independent and permit its application to any image projected under different view angle and/or acquired with different image-intensifier system. The correction leads to a nearly distortion-free image. PMID- 1511399 TI - Projection domain compensation of missing angles for fan-beam CT reconstruction. AB - An improved method is proposed for fan-beam computed tomographic (CT) reconstruction from data with limited views. Compensation for the missing projections for fan-beam CT can be partially accomplished by using the coincident ray or by an interpolation technique using circular sample theory. In this article, the authors propose a more accurate compensation method for the missing projections whether the coincident ray pairs exist or not. The fan-beam reprojection algorithm, which is the inverse operator of the convolution filter, was extended from the projection space iteration reconstruction-reprojection (PSIRR) in parallel beam geometry. In addition, this algorithm was validated by applying the Shepp-Logan phantom for a computer simulation in the equi-angular fan-beam CT geometry. PMID- 1511400 TI - Fluorescence photograph of stomach cancer tumors in Wistar rats: computerized analysis. AB - Detection of cancer in early stages with hematoporphyrin derivatives (HpD) is highly limited by the low fluorescence quantum yield, the strong autofluorescent components of the tissue, and the low contrast between normal and tumoral tissue when fluorescent photographs are taken. A new computer analysis based on digital subtraction of photographs before and after the administration of HpD, allows a total autofluorescence extraction, resulting in a remarkable increase of contrast between tumors and normal tissue. Experiments, with this computerized imaging system in adenocarcinoma of the stomach in Wistar rats, confirms the reliability of this method. PMID- 1511401 TI - Intracanalicular arachnoid cyst mimicking acoustic neuroma: CT and MRI. AB - A patient with a surgically proven intracanalicular arachnoid cyst was studied using computed tomography, magnetic resonance imaging, and air CT cisternography. The lesion had a similar radiographic appearance to acoustic neuroma and therefore, although rare, must be considered in the differential diagnosis of intracanalicular mass lesions. We report a case in which examination was performed, in evaluating the lesion, utilizing high-resolution air CT cisternography and magnetic resonance imaging (MRI). PMID- 1511402 TI - Epithelioid hemangioendothelioma of spleen with intrasplenic metastasis: ultrasound and computed-tomography appearance. AB - The US and CT appearances of epithelioid hemangioendothelioma of the spleen with intrasplenic metastasis have not been previously reported. We described a 29-yr old female with such a disease. Abdominal US study revealed a large mass in the upper pole and multiple small nodules in the rest of the spleen. CT scan also showed similar lesions of hypodensity which were not apparently enhanced by contrast medium. PMID- 1511403 TI - Acute pyelonephritis after transrectal ultrasonographically guided biopsy of the prostate: diagnosis by computed tomography. AB - Acute pyelonephritis developed in a 67-yr-old man after transrectal ultrasonographically guided biopsy of the prostate. The clinical presentation and results of excretory urography were nondiagnostic. Diagnosis was made by computed tomography, which was delayed 12 h after i.v. administration of contrast medium. PMID- 1511404 TI - Modification of tumor promotion in the mouse skin by exposure to an alternating magnetic field. AB - Some epidemiological studies have suggested that exposure to an alternating magnetic field may increase the incidence of some cancers. Our earlier study of carcinogenesis in mouse skin, indicated that exposure to a magnetic field (MF) alone did not promote the growth of tumors. In the present experiment, the ability of a MF to act as a tumor copromoter was investigated. The dorsal skins of female SENCAR mice (6-7-weeks-old) were treated with 10 nmol of 7,12 dimethylbenzanthracene (DMBA) to initiate the carcinogenic process and then tumor development was promoted, for 23 weeks, by weekly applications of 4.9 nmol (0.3 microgram) of 12-0-tetradecanoylphorbal-13-acetate (TPA). One group of 48 mice were exposed to a 60-Hz magnetic field of 2 mT (20 Gauss) for 6 h/day 5 days/week, while a similar group (48 mice) were sham exposed. After week 12, the percentage of mice with tumors and the mean number of tumors per mouse, were higher for the group exposed to MF. At week 18, for example, where the differences between field and sham groups were statistically significant, the percentage of mice with tumors were, respectively, 25% and 8% (P less than 0.05, Fisher exact) and, the mean yield of tumors 1.9 +/- 0.69 and 0.65 +/- 0.46 (mean +/- S.E.M.) (P less than 0.05, Wilcoxon). At week 23 these differences were no longer statistically significant. PMID- 1511405 TI - Ammonia: a possible promotor in Helicobacter pylori-related gastric carcinogenesis. AB - Helicobacter pylori (HP) has been shown to possibly be a pathogen of gastric carcinoma. HP has urease activity and produces ammonia in the stomach. In this study, the role of ammonia on gastric carcinogenesis induced by N-methyl-N'-nitro N-nitrosoguanidine (MNNG) were investigated in rats. After 24 weeks pretreatment with MNNG (83 mg/l), 0.01% ammonia or tap water as a drinking water was administered for 24 weeks. The ammonia-treated rats showed a significantly higher incidence of gastric cancer (percent of animals with tumors and number of tumors per rat). Ammonia would thus appear to have an important role in HP-related human gastric carcinogenesis. PMID- 1511406 TI - Analysis of the Harvey ras gene in cisplatin-initiated mouse skin tumors by polymerase chain reaction and direct DNA sequencing. AB - Cisplatin (cis-dichlorodiammineplatinum (II)) acts as a tumor initiator in the mouse skin model of carcinogenesis. DNA transfection studies suggested that skin tumors initiated by cisplatin contained dominant transforming activity. Since the Harvey-ras (H-ras) gene is known to be activated by point mutations in chemically initiated mouse skin tumors, we used polymerase chain reaction (PCR) and direct DNA sequencing to analyze the DNA sequence of the H-ras gene in twelve different cisplatin-initiated skin tumors. The results of these studies indicated that cisplatin-initiated skin tumors were normal (wild-type) at codons 12, 13, 61 and 117. Thus the transforming activity associated with cisplatin initiated mouse skin tumors was not due to a mutant H-ras gene and this suggests the involvement of other transforming genes during initiation of the mouse skin with cisplatin. PMID- 1511407 TI - Detection of PAH:DNA adducts from auto-oxidation using 32P-postlabeling. AB - The binding of benzo[a]pyrene, 7,12-dimethylbenz[a]anthracene, 3 methylcholanthrene, benz[a]anthracene, dibenz[a,c]anthracene and phenanthrene to calf thymus DNA in vitro in the absence of enzymatic or chemical activation was investigated using the 32P-postlabeling assay. Reactions were performed in the dark or under white light in 1 ml of Tris-HCl buffer (pH 7.5), containing 150 mM KCl, 250 micrograms of DNA and 0.12 nmol-600 nmol of hydrocarbon. Reactions were incubated for 1 h at 37 degrees C and the extent of hydrocarbon:DNA adduct formation was determined. With the exception of phenanthrene, all of the hydrocarbons investigated formed DNA adducts that were easily detected with the 32P-postlabeling assay. The multiplicity and level of hydrocarbon:DNA adducts varied for each hydrocarbon. A dose related increase in adduct formation was observed. Adduct levels ranged from 0.07 to 15.28 adducts per 10(7) nucleotides. Highest adduct levels were detected with 7,12-dimethylbenz[a]anthracene (DMBA) and benzo[a]-pyrene (B[a]P). Hydrocarbon: DNA adduct formation was enhanced when reactions were performed under white light. A comparison of the adduct levels formed from auto-oxidation and enzymatic activation suggests that 0.05 and 0.26% of the adducts detected in the enzymatic activation of B[a]P and DMBA, can be attributed to auto-oxidation, respectively. These data demonstrate that in the absence of enzymatic or chemical activation, polycyclic aromatic hydrocarbons can undergo auto-oxidation in vitro and form hydrocarbon:DNA adducts that are detectable with the 32P-postlabeling assay. PMID- 1511408 TI - Inhibition by selenium of DNA and RNA synthesis in normal and malignant human cells in vitro. AB - Several studies have demonstrated differences between normal and malignant cells in their sensitivity to various effects of selenite. We have compared the effect of selenite on DNA and RNA synthesis in two pairs of normal and malignant human cell lines. One pair of cells, CCL-210 (normal lung fibroblasts) and A549 (lung adenocarcinoma cells), exhibited a large difference in their sensitivity to selenite but no significant difference in their sensitivity to selenodiglutathione. They also had a large difference in the level of intracellular sulfhydryl (SH) compounds. In contrast the other pair of cells, WI 38 (normal fetal lung fibroblasts) and WI-38VA (SV-40 transformed WI-38 cells) both had low levels of intracellular SH compounds and exhibited similar (low) sensitivity to selenite. Our results indicate that differences between normal and malignant cells in their sensitivity to selenite could be due to a difference in the reaction of selenite with intracellular sulfhydryl compounds to form selenotrisulfides. PMID- 1511409 TI - Effect of (-)-epigallocatechin gallate, the main constituent of green tea, on lung metastasis with mouse B16 melanoma cell lines. AB - (-)-Epigallocatechin gallate (EGCG), the main polyphenolic constituent of green tea, inhibits tumor promotion and chemical carcinogenesis in animal experimental systems. Here we report that the peroral administration of EGCG inhibited metastasis of B16 melanoma cell lines, such as B16-F10 and BL6, in both experimental and spontaneous systems. PMID- 1511410 TI - Comparative reduction of 1-nitro-3-nitrosopyrene and 1-nitro-6-nitrosopyrene: implications for the tumorigenicity of dinitropyrenes. AB - Dinitropyrenes are mutagenic environmental pollutants. Of these compounds, 1,6 dinitropyrene is a potent tumorigen while 1,3-dinitropyrene appears to be weakly or non-tumorigenic. Two-electron reduction of dinitropyrenes yields nitro nitrosopyrenes, which have been shown previously to be the major aerobic metabolites of these compounds in vitro. Further reduction of nitrosopyrenes is required for their activation to a DNA-reactive N-hydroxylamines. In this work, 1 nitro-3-nitrosopyrene was synthesized and the electrochemical and enzyme catalyzed reduction of 1-nitro-3-nitrosopyrene has been compared with that of 1 nitro-6-nitrosopyrene. As determined by cyclic voltammetry, the reduction potentials of 1-nitro-3-nitrosopyrene, 1-nitro-6-nitrosopyrene and their parent dinitropyrenes were similar, although 1-nitro-3-nitrosopyrene did have a slightly more negative cathodic peak potential than the other three compounds. The NADPH mediated reduction of 1-nitro-6-nitrosopyrene to intermediates which reduce succinoylated cytochrome c was faster than that of 1-nitro-3-nitrosopyrene. In the presence of rat liver microsomes or cytosol, the reduction of 1-nitro-6 nitrosopyrene was faster than that of 1-nitro-3-nitrosopyrene. These differences in the rates of nitro-nitrosopyrene reduction may be one factor contributing to the lower tumorigenic potential of 1,3-dinitropyrene relative to 1,6 dinitropyrene. PMID- 1511411 TI - Antitumor activity of polysaccharide from a Chinese medicinal herb, Acanthopanax giraldii Harms. AB - The results of experiments with Acanthopanax giraldii polysaccharide (AGP) demonstrated that it inhibited the growth of solid Sarcoma 180 and prolonged the survival time significantly. In tumor-bearing mice, AGP enhanced the phagocytosis and chemiluminescence of macrophages. By the immunofluorescent method, binding of the third component of complement (C3) cleavage product to macrophages and proportion of C3 positive cells were increased. In crossed immunoelectrophoresis, human serum C3 was converted by AGP and appeared as the 3rd peak. The height of the 3rd peak was directly proportional to doses of AGP. The residual CH50 units of human serum decreased dose-dependently. These results suggest that the antitumor activity of AGP is related to the enhancement of immune responses. PMID- 1511412 TI - Endocrine mediation of psychosocial stressor effects on mouse mammary tumor growth. AB - We have demonstrated that differential housing alters the growth rate of the androgen-responsive Shionogi mouse mammary carcinoma (SC115). In the present study we wished to determine if changes in plasma levels of hormones or a shift in the responsiveness of the tumor cells to hormones was responsible for the differential tumor growth rates observed. Plasma testosterone and corticosterone levels were assayed 24 h, 3 days and 1 week post tumor cell/vehicle injection. Also 3 weeks post injection androgen and glucocorticoid receptor binding capacity (Bmax) and binding affinity (Kd) and the in vitro responsiveness of tumor cells to dihydrotestosterone and hydrocortisone were measured. At 24 h post injection, plasma testosterone levels were significantly increased in mice with large tumors, but remained low in mice with small tumors. Plasma corticosterone levels were significantly elevated in mice with small tumors compared to those of mice with large tumors at all time points measured. Androgen and glucocorticoid receptor binding capacity and binding affinity of tumor cells did not differ among groups. Further, all groups tested had the ability to respond to dihydrotestosterone and hydrocortisone in vitro. These data indicate that an effect of housing condition on plasma levels of steroid hormones may, in part, mediate the differential tumor growth rates observed in this model. PMID- 1511413 TI - Antitumor activity of phytic acid (inositol hexaphosphate) in murine transplanted and metastatic fibrosarcoma, a pilot study. AB - We have previously reported that phytic acid (inositol hexaphosphate or InsP6), a natural constituent of cereal diet, when administered in drinking water exerts a consistent antitumor effect on experimental colon cancer in vivo. The objective of this study was to determine whether InsP6 has similar anti-neoplastic effect on other tumor models, such as murine fibrosarcoma. We report that intraperitoneal injection of InsP6 reduces growth of subcutaneously transplanted fibrosarcoma (FSA-1) in mice, prolongs survival of tumor-bearing mice and reduces the number of pulmonary metastases. Since InsP6 is a common constituent of our diet and has very little or no toxic effects, in addition to being chemopreventive, it could have potential use in therapy of cancer as well. PMID- 1511414 TI - A study of tobacco carcinogenesis. XLVII. Bioassays of vinylpyridines for genotoxicity and for tumorigenicity in A/J mice. AB - 3-Vinylpyridine is formed from nicotine during the smoking of tobacco products. Consequently it is found in mainstream and side-stream smoke of cigarettes and cigars and in environmental tobacco smoke. In this study, 3-vinylpyridine and its isomers 2- and 4-vinylpyridine as well as styrene (vinylbenzene) were bioassayed for mutagenicity in Salmonella typhimurium strains TA 1535, TA 1538, TA 98 and TA 100 and for their genotoxicity in the rat hepatocyte DNA-repair test. In both in vitro assays-all three vinylpyridines and styrene were inactive. In a test for tumorigenicity in which the test compounds were injected intraperitoneally into A/J mice (total dose 200 mumol/animal) there was no significant incidence of lung adenoma nor of any other type of tumors. PMID- 1511415 TI - Parallel changes in the blood levels of abnormally-fucosylated haptoglobin and alpha 1,3 fucosyltransferase in relationship to tumour burden: more evidence for a disturbance of fucose metabolism in cancer. AB - Levels of an abnormally-fucosylated form of the serum glycoprotein, haptoglobin (FHp) and an enzyme, alpha 1,3 fucosyltransferase (FT) have been measured in blood specimens from women with carcinoma of the ovary or breast who are undergoing chemotherapy. The levels of FHp and FT increased if the women had progressive disease and decreased if they showed complete response to therapy. The statistical correlation between the blood concentrations of these two substances is very strong (P less than 0.0001, chi 2 test). These results and recent studies of fucosyltransferases and cell adhesion molecules from other laboratories, suggest that there are important changes in fucose metabolism in cancer which are worthy of further investigation. PMID- 1511416 TI - The effect of EDTA and serum on endogenous porphyrin accumulation and photodynamic sensitization of human K562 leukemic cells. AB - The interrelationship between the effect of serum on the induction of porphyrin synthesis, intracellular porphyrin accumulation and photodynamic sensitization of human K562 cells is described. Endogenous porphyrins, synthesized from supplemented 5-amino levulinic acid (5-ALA), were shown to accumulate in the cells, while an addition of serum triggered porphyrin translocation from the cell to the serum. In order to enhance porphyrin accumulation in the cells themselves, they were further stimulated by EDTA, which in combination with 5-ALA reduces Fe++ cellular content. The higher porphyrin cellular content under EDTA and 5-ALA induction was exploited to photoinactivate the human leukemic cells by more then 3 orders of magnitude. PMID- 1511417 TI - Inhibitory effect of geniposide on aflatoxin B1-induced DNA repair synthesis in primary cultured rat hepatocytes. AB - We have previously demonstrated that geniposide (GP) inhibits the aflatoxin B1 (AFB1) induced-hepatotoxicity and hepatic DNA binding in rats. To address the mechanism of action, the effects of GP on AFB1-induced DNA repair synthesis and AFB1 biotransformation in cultured rat hepatocytes were investigated. By evaluation of unscheduled DNA synthesis (UDS), GP reduced AFB1-induced DNA repair synthesis in a dose-dependent manner in hepatocyte cultures. GP elevates the metabolism of AFB1 and decreases the formation of AFM1. The enzyme activities of glutathione S-transferase (GST) and GSH-peroxidase (GSH-Px) in AFB1-treated hepatocyte cultures are enhanced in the presence of GP. GP reduces AFB1-induced DNA repair synthesis through an increased AFB1 detoxication metabolism. It provides one possible mechanism for the chemopreventive activity of GP. PMID- 1511418 TI - Effect of dietary nitrate on endogenous nitrosation of piperazine in humans. AB - The effect of dietary nitrate on endogenous nitrosation of a therapeutic dose of piperazine has been described in five human volunteers who acted as their own controls. The urinary excretion of endogenously formed N-nitro-somonopiperazine (MNPz) ranged between 9.2 and 80.1 micrograms/24 h on a normal uncontrolled diet which increased from 25.7 to 163.7 micrograms/24 h when the diet was supplemented with 250 mg nitrate. The corresponding urinary nitrate was 63.0-122.7 mg/24 h and 119.2-322.0 mg/24 h, respectively. The dinitroso derivative of piperazine was detected only in trace amounts and no detectable increase in its excretion was observed during high nitrate exposure. The unchanged piperazine (range 294-784 mg/24 h) in urine showed a decrease under high nitrate regimen (range 185-399 mg/24 h). PMID- 1511419 TI - Si(IV)-naphthalocyanine: modulation of its pharmacokinetic properties through the use of hydrophilic axial ligands. AB - A water-soluble derivative of the highly hydrophobic molecule Si(IV) naphthalocyanine was synthesized by the addition of two polyethyleneglycol ligands in axial positions to the centrally coordinated Si(IV) ion. The compound can be intravenously injected in homogeneous aqueous solution, where it is largely aggregated and remains mostly in an unbound state. While the naphthalocyanine is accumulated in significant amounts by an intramuscularly transplanted MS-2 fibrosarcoma in Balb/c mice, the dye shows little tumour selectivity and essentially no phototherapeutic activity. The situation is not improved by association of the naphthalocyanine with dipalmitoyl phosphatidylcholine liposomes, probably owing to a lack of incorporation of the bulky dye molecule into the phospholipid bilayer. PMID- 1511420 TI - Promotion pattern and tumour types in two-stage rat skin carcinogenesis. AB - Carcinogenic studies were performed on the skin of inbred male Lister rats using 7,12-dimethylbenz[alpha]anthracene (DMBA) in low doses (2.5 mg and 5.0 mg), followed by promotion with croton oil (CO) in one half of the animals. The clinically observed tumour rate did not differ after the two carcinogen doses and was practically unaffected by promotion, only a marginal increase in effect being noted after DMBA 2.5 mg. Also the latency periods were alike. The total tumour crop was increased by promotion, but histologically the predominant clinical skin tumour was a sebaceous proliferation with or without associated papillomatous squamous cell hyperplasia. This lesion did not in microscopic structure or cellular characteristics fulfil the criteria of a neoplastic tumour. Basal cell carcinomas, adnexal tumours and pure squamous cell tumours were rare and were not promoted by CO. CO had a marked promotion effect, but only on the mixed sebaceous papillomatous hyperplasias, which were more than doubled in number. In conclusion, carcinogenesis was weak after the low DMBA-doses, and promotion by CO of neoplastic tumours was not seen. PMID- 1511421 TI - HPLC separation of 32P-postlabelled benzo[b]fluoranthene-DNA adducts. AB - Analysis using 32P-postlabelling and a recently developed HPLC method resolved the adduct formed by reaction of the benzo[b]fluoranthene (BbF) anti-bay-region diol-epoxide with DNA from the more polar major adduct produced by the hydrocarbon in three different biological systems. In each case, the adduct formed from the anti-bay-region diol-epoxide constituted only a minor proportion of the total DNA modification. Comparisons of the DNA adducts formed from the hydrocarbon with those formed in microsomal incubations from the putative metabolites BbF-9,10-diol, anti-BbF-9,10-diol-11,12-oxide and the 5,9,10- and 6,9,10-BbF-triols indicate that the predominant pathway for BbF activation in skin probably involves a bay-region triol-epoxide possessing a phenolic OH-group on the peninsula ring. PMID- 1511422 TI - Tissue lipid composition of human gliomas and meningiomas. AB - This study is a comparative analysis of some lipid fractions in human brain tumors and normal brain tissue. Gliomas and meningiomas were studied and in these tumors while total lipid, total and free cholesterol and total phosphoglyceride levels were found to be significantly lower than in normal controls, the difference in esterified cholesterol levels was found to be insignificant. No significant differences in lipid fractions existed between gliomas and meningiomas except total and esterified cholesterol values. PMID- 1511423 TI - Variable expression of the interleukin-2 receptor alpha chain and MYC genes in lymphocytes from renal cell carcinoma patients treated with interleukin-2. AB - We have studied the expression of the interleukin-2 receptor alpha chain, c-MYC and L-MYC genes in lymphocytes obtained from four renal cell carcinoma patients undergoing an interleukin-2 clinical trial. Two of these patients exhibited stable disease after the interleukin-2 therapy and two exhibited progressive disease. Analysis of mRNA levels by dot blot hybridization indicated that changes in the expression of both the interleukin-2 receptor alpha chain and c-MYC genes were erratic and varied widely between patients. L-MYC expression was not observed in any sample. There appeared to be little correlation between the changes in gene expression and parameters such as thymidine incorporation, the proportion of CD25 positive cells present or cytotoxic activity. The situation in vivo therefore appears to be more complex than would be predicted from in vitro studies. PMID- 1511424 TI - Effect of verapamil on the class I major histocompatibility complex antigen expression in K562 chronic myelogenous leukemia cells treated with recombinant human interferon-gamma. AB - The effects of various compounds which modulated the intracellular signal transduction on the induction of class I major histocompatibility complex (MHC) antigens by recombinant human interferon-gamma (rIFN-gamma) were investigated using K562, chronic myelogenous leukemia cells. Class I or class II MHC antigens were not expressed in untreated K562 cells and rIFN-gamma (600 units/ml) weakly induced class I antigens on the cells. Among the compounds tested, verapamil but not the calcium ionophore A23187 enhanced the rIFN-gamma-induced class I antigen expression at both the surface molecule and mRNA levels and enhancement by verapamil occurred in a dose-dependent manner at non-toxic concentrations examined (approximately 50 microM). Verapamil alone had no inducible effect on MHC antigen expression. Deprivation of Ca2+ in culture medium by ethylene glycol bis(beta-aminoethyl ether) N,N,N',N'-tetraacetic acid (EGTA) could not cause an enhancement of class I antigen induction by rIFN-gamma. Simultaneous exposure of K562 cells to rIFN-gamma (600 units/ml) and recombinant human tumor necrosis factor (rTNF; 1000 units/ml) in combination with verapamil (50 microM) resulted in a further increase of class I antigens in the cells. The expressions of c-myc oncogene in K562 cells were not changed when the cells were treated with rIFN gamma (600 units/ml) or verapamil (50 microM), either alone or in combination. These results indicate that verapamil synergistically interacts with rIFN-gamma on the class I antigen induction in K562 cells irrespective of c-myc gene expression and that class I antigen induction in this cell line may not be relevant to calcium influx triggered by IFN-gamma. PMID- 1511425 TI - In vivo and in vitro growth-inhibitory effect of bovine seminal ribonuclease on a system of rat thyroid epithelial transformed cells and tumors. AB - We investigated the antitumoral effect of bovine seminal RNase (BS-RNase) in vivo and in vitro on a model system of epithelial tumor- and metastasis-derived cells as well as on epithelial tumors derived from the same system. We found that while BS-RNase significantly inhibited the growth in vitro of the epithelial tumor derived cells, its inhibitory effect was even more dramatic on the growth of metastasis-derived cells. BS-RNase exerted no appreciable growth inhibition on normal thyroid epithelial cells. When administered in vivo to rats bearing solid carcinomas, having the same thyroid origin, BS-RNase induced a drastic reduction in the tumor weight, with no detectable toxic effects on the treated animals. These data show, for the first time on a system of neoplastically transformed epithelial cells, that BS-RNase has a potent specific antitumoral activity. PMID- 1511426 TI - Clinical implications of decreased retinoblastoma protein expression in acute myelogenous leukemia. AB - The retinoblastoma (RB) protein levels in blast-enriched mononuclear fractions from the peripheral blood of 33 newly diagnosed patients with acute myelogenous leukemia were studied. Ten patients who had previously been treated were also analyzed, nine of whom had achieved prior complete remission. Low RB protein expression was found in 13 of 43 (30%) of the acute myelogenous leukemia patients as determined by Western blotting and immunochemical analysis. Of particular interest among the 20 newly diagnosed patients treated with the same therapeutic regimen, the median survival was 39 days for those with low RB protein expression compared to 333 days for those with high levels of RB protein expression in their leukemic cells (P less than or equal to 0.02). This preliminary study suggests that decreases of RB protein expression in peripheral blood of myeloid leukemic cells occur frequently and may be associated with shortened survival of acute myelogenous leukemia patients. PMID- 1511427 TI - Cell cycle synchronization and growth inhibition by 3-hydroxypyridin-4-one iron chelators in leukemia cell lines. AB - The effect of bidentate 3-hydroxypyridin-4-one (HPO) iron chelators on cell cycle arrest with subsequent cycle synchronization has been compared with that of the hexadentate desferrioxamine (DFO) in K562 and Daudi cells. The relationships between chelator concentration and inhibition of growth, DNA synthesis and ribonucleotide reductase, and phase of cell cycle arrest have also been explored. HPOs and DFO arrest the cell cycle in a dose-dependent manner causing a blockade at the G1-S border after 24 h at concentrations above 30 microM iron-binding equivalents. This is associated with reduced ribonucleotide reductase activity and concomitant cessation of DNA synthesis and growth. When the chelator is subsequently removed, HPO-treated cells synchronously cascade into S phase, unlike DFO-treated cells which resume cycling in a nonsynchronous manner. Chelator concentrations of approximately 25 microM and 3 microM iron-binding equivalents inhibited growth, DNA synthesis, and ribonucleotide reductase activity by 50% in K562 and Daudi cells, respectively. Concentrations less than 10 microM iron-binding equivalents inhibited K562 cell growth without an effect on DNA synthesis but with accumulation of cells in G2 and M phases. These results suggest that HPOs have advantages over DFO as cell cycle synchronization agents and may be useful adjuncts in cell cycle-specific treatment regimens. PMID- 1511428 TI - Effect of treatment duration and glutathione depletion on mitomycin C cytotoxicity in vitro. AB - Glutathione (GSH) has been shown to modulate the cytotoxicity of a variety of chemotherapeutic agents. The effect of mitomycin C (MMC) treatment duration and the effect of GSH depletion on in vitro cytotoxicity against the human colon cancer cell line HT-29 was studied under aerobic conditions. Continuous-exposure experiments revealed that the cytotoxicity of 0.1 microM MMC, as measured by clonogenic cell survival, exhibited a shoulder until exposure time was at least 12 h, after which time exponential cytotoxicity was observed. Lowering GSH levels to less than 3% of control using buthionine sulfoximine (BSO) did not enhance cytotoxicity of MMC given for 1 h or continuously for less than 12 h. However, GSH depletion did enhance cytotoxicity of MMC given continuously for at least 12 h, with a dose-modifying factor at 1% survival of 1.4 for a 24-h treatment. GSH depletion under these conditions enhanced cytotoxicity of even minimally cytotoxic MMC concentrations (0.02 microM). Absolute levels of GSH-related enzymes, including glutathione-S-transferase, and the MMC-metabolizing enzyme DT diaphorase did not change appreciably. A tetrazolium [3-(4,5-dimethylthiazol-2 yl)-2,5-diphenyl tetrazolium bromide] assay was used to verify the results further and to determine the optimal sequence of BSO administration with a 24-h MMC treatment. BSO added simultaneously with MMC did not increase cytotoxicity, compared to MMC alone. BSO added and then removed prior to MMC was effective (dose-modifying factor at 50% survival = 1.3), but the greatest cytotoxicity was noted when BSO was present before and during MMC treatment (dose-modifying factor = 1.5). GSH depletion in another cell line (SW480) showed similar enhancement of 24-h MMC cytotoxicity. These studies show that aerobic cytotoxicity of MMC is improved by administration of the drug in continuous fashion for at least 12 h, as opposed to continuous administration for shorter periods or 1-h bolus administration. Cytotoxicity of continuous (at least 12-h) MMC treatment can be modestly enhanced by GSH depletion, which must precede MMC exposure in order to be effective. PMID- 1511429 TI - Rat prostate adenocarcinoma cells disseminate to bone and adhere preferentially to bone marrow-derived endothelial cells. AB - Approximately 70% of patients with prostatic cancer develop bone metastases. Metastatic prostate adenocarcinomas are associated with high mortality rates and represent a leading cause of cancer-related deaths among males. To study the host tumor interactions underlying the predilection of prostate cancer cells for skeletal bone, an experimental model was developed using rat Dunning carcinoma Mat-LyLu cells. Inoculations of these cells into the left ventricle of the heart led to the development of spinal metastases in 100% of inoculated animals. A subline of Mat-LyLu (Mat-LyLu-B5) was subsequently selected through the sequential inoculation of bone marrow-derived carcinoma cells into the left ventricle and was found to have an increased metastatic potential compared to the parental line. The possible role of tumor cell adhesion to host cells in the process of bone marrow colonization was then investigated in vitro using the metastatic line and primary cultures of rat bone marrow-derived stromal cells. It was found that the adhesion of the metastatic Mat-LyLu cells to a bone marrow stromal cell culture highly enriched for endothelial cells was significantly higher than the adhesion to other bone-derived cells, including nonendothelial bone marrow stromal cells (3.5x) and osteoblasts (1.7x). It was also significantly higher than the adhesion to rat fibroblasts (7x) and to hepatic endothelial cells (7.5x). The results suggest that the adhesion of prostate carcinoma cells to the bone marrow endothelium may play a role in their metastasis to bone. PMID- 1511430 TI - Quantitative changes in tumor metabolism, partial pressure of oxygen, and radiobiological oxygenation status postradiation. AB - Hypoxia is considered to be a major cause of tumor radioresistance. Reoxygenation of previously hypoxic areas after a priming dose of radiation is associated with an increase in tumor radiosensitivity. In a study of a hypoxic mammary carcinoma, 31P nuclear magnetic resonance spectra showed statistically significant increases in metabolite ratios (phosphocreatine/Pi and nucleotide triphosphate/Pi) after 65 and 32 Gy. The maximum changes in metabolite ratios after 32 Gy occurred at 48 h, although significant changes were detected at 24 h. A corresponding increase in the mean tumor pO2 (polarographic microelectrode measurements) and a decrease in hypoxic cell fraction [changes in paired (clamped versus unclamped) tumor control dose for 50% of tumors] were also shown to occur 48 h after a priming dose of 32 Gy. A significant increase in the mean tumor pO2, phosphocreatine/Pi, and nucleotide triphosphate/Pi, compared to initial values, was noted at 24, 48, and 96 h post 65-Gy radiation. An increase in the downfield component of the phosphomonoester peak relative to the upfield component (phosphoethanolamine), is also noted after doses of 65 and 32 Gy. These are likely to be due to cell kill and/or decreased cell proliferation. In this tumor model, 31P nuclear magnetic resonance spectroscopic changes postradiation are temporally coincident with and may be indicative of tumor reoxygenation as measured by the tumor control dose for 50% of tumors and oxygen-sensitive microelectrodes. PMID- 1511431 TI - Expression and characterization of mucins associated with the resistance to methotrexate of human colonic adenocarcinoma cell line HT29. AB - A series of experiments were conducted to study synthesis and secretion of mucin in mucus-secreting subpopulations of HT29 human colonic adenocarcinoma cells selected by resistance to methotrexate (MTX). Mucin was quantitated by [3H]glucosamine labeling and chromatography on Sepharose CL-4B. The mucinous nature of the labeled high molecular weight glycoprotein was verified by alkaline borohydride treatment, cesium chloride density gradient ultracentrifugation, and sodium dodecyl sulfate-polyacrylamide gel electrophoresis. The results of these experiments demonstrated that MTX-treated cells have increased amounts of mucin in medium, cytosol, and membrane fractions. This was associated with the increase in the activities of polypeptidyl-N-acetylgalactosaminyltransferase and beta-1,3 galactosyltransferase compared to control cells. DEAE-Sephacel chromatography of [3H]glucosamine-labeled high molecular weight glycoproteins suggest that MTX treated cells are less acidic compared to controls. Using complementary DNA probes for two distinct human intestinal mucins (MUC2 and MUC3) and one mammary mucin (MUC1), it was found that MTX-treated cells expressed more mucin messages compared to untreated cells. These results were consistent with immunoblots using anti-MRP (MUC2 repeat peptide), anti-M3P (MUC3 repeat peptide), 139H2 (MUC1 peptide), anti-T (peanut lectin), anti-Tn (91S8), and anti-sialosyl Tn (JT10e) antibodies. These data indicate that MTX-resistant HT29 cells show enhanced secretion and synthesis of mucin as well as expression of MUC1-, MUC2-, and MUC3 related mucin polypeptide epitopes. PMID- 1511432 TI - Comparative antitumor effects of hormonal ablation, estrogen agonist, estrogen cytotoxic derivative, and antiestrogen in the PAIII rat prostatic adenocarcinoma. AB - The effects of hormonal ablation, estrogen, estrogen-derived cytotoxic agent, and estrogen antagonist therapies used clinically were evaluated on in vitro colony formation, in vivo growth, and lymphatic and pulmonary metastasis of the PAIII tumor. Ventral prostatic and seminal vesicle weights were evaluated in the same animals to assess androgen-related responses. Estradiol, estramustine phosphate, and testosterone had no effects on PAIII colony formation in vitro. Castration, hypophysectomy, estradiol benzoate, and estramustine phosphate treatment of PAIII bearing Lobund Wistar rats produced significant (P less than 0.05) regression of male accessory sex organs. Of these treatments, only hypophysectomy had significant (P less than 0.05) inhibitory effects on primary PAIII growth and lymphatic and pulmonary metastasis. LY117018 [6-hydroxy-2-(p hydroxyphenyl)benzo(b)thien-3-yl-p-2-(l-pyrrolidin yl)ethoxy phenyl ketone] has antiestrogenic activity but produces no significant agonist responses. LY117018 had no effect upon PAIII colony formation in vitro. Following s.c. implantation of PAIII cells, LY117018 (2.0, 10.0, or 20.0 mg/kg s.c.) had no effect on primary tumor growth in the tail. In vitro LY117018 administration produced marked antimetastatic effects. In a dose-dependent manner, LY117018 inhibited PAIII metastasis to the gluteal (97%) and iliac lymph nodes (88%) (P less than 0.05 for both). LY117018 also maximally inhibited pulmonary metastasis by 86% (P less than 0.05). Maximal regression of 42% for ventral prostatic and 35% for seminal vesicle weights were also seen after LY117018 administration (P less than 0.05 for both). Co-administration of estradiol benzoate had no antagonistic effect upon the antitumor responses produced by LY117018. The mechanism of action of LY117018 is not known. The failure of estradiol benzoate to affect PAIII growth and metastasis supports the contention that the responses to LY117018 are not attributable to simple antagonism of estrogen action. LY117018 may be exerting its antitumor effects through autocrine, paracrine, or endocrine mechanisms. LY117018 represents a class of agents with potential utility in treating metastatic cancer of the prostate. PMID- 1511433 TI - Boron neutron capture therapy for murine malignant gliomas. AB - Boron neutron capture therapy (BNCT) involves administration of a boron compound followed by neutron irradiation of the target organ. The boron atom captures a neutron, which results in the release of densely ionizing helium and lithium ions that are highly damaging and usually lethal to cells within their combined track length of approximately 12 microns. Prior to Phase I clinical trials for patients with malignant gliomas, mice with glioma 261 intracerebral tumors were fed D,L-3 (p-boronophenyl)alanine and irradiated with total tumor doses of 1000-5000 RBE cGy of single fraction thermal neutrons to determine the maximum tolerated dose and effect on survival. These mice were compared to mice that received D,L-3-(p boronophenyl)alanine alone, neutron irradiation alone, photon irradiation alone, or no treatment. Additional normal mice received escalating doses of neutron irradiation to determine its toxicity to normal brain. BNCT caused a dose dependent, statistically significant prolongation in survival at 1000-5000 RBE cGy. At 3000 RBE-cGy, median survival rates of the BNCT and untreated control groups were 68 and 22 days, respectively, with a long-term survival rate of 33%. At 4000 RBE-cGy, median survival was 72 and 21 days, respectively, with a long term survival rate of 43%. At lower radiation doses, the extended survival was comparable between the BNCT and photon-irradiated mice; however, at 3000 and 4000 RBE-cGy the median survival of BNCT-treated mice was significantly greater than photon-irradiated mice. The maximum tolerated single fraction dose to normal brain was approximately 2000 RBE-cGy. PMID- 1511434 TI - Fate and distribution of 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine in mice at a human dietary equivalent dose. AB - 2-Amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) is a heterocyclic amine rodent carcinogen that is found at the ppb level in cooked meat. Most laboratory studies are at 10(4)-10(7)-fold greater concentrations than actual ingested human doses. We report the first study of the bioavailability and fate of this heterocyclic amine at a human dietary equivalent dose using the high sensitivity offered by accelerator mass spectrometry. [2-14C]PhIP was administered to C57BL/6 male mice (41 ng/kg) by gavage. Tissues and excreta were collected over the subsequent 96 h. One hundred % of the administered dose was excreted in urine (90%) and feces (10%) over the length of the study. Absorption of the radiocarbon tagged PhIP from the gastrointestinal tract was rapid, with radiocarbon levels peaking in the whole blood and urine within 1 h of exposure. Fecal 14C levels peaked at 12 h. Tissue levels peaked by 3 h with the highest concentrations of radiolabel in the intestine, stomach, and liver, followed by the kidney, pancreas, lung, and spleen. Low levels of 14C from PhIP (0.01-0.04% of the administered dose) could be detected in the tissues 48-96 h after exposure, possibly due to covalent binding to protein or DNA. The calculated half-life of PhIP at this dose was 1.14 h. This study is the first example of how accelerator mass spectrometry can be used to gather biological information about carcinogenic compounds at environmental levels of exposure. PMID- 1511435 TI - Mutational specificity of 1,3-bis-(2-chloroethyl)-1-nitrosourea in a Chinese hamster ovary cell line. AB - The mutational specificity of the alkylating agent 1-3-bis-(2-chloroethyl)-1 nitrosourea (BCNU) was analyzed at the endogenous hemizygous adenine phosphoribosyl transferase gene of the Chinese hamster ovary cell line D422. A 1 h treatment of the Chinese hamster ovary cells with 50 microM BCNU resulted in a toxicity level of 62% and induced mutation at this target with a frequency of 32.1 mutants/10(6) survivors (6-fold above background). Analysis of 49 BCNU induced mutants at the DNA sequence level revealed that BCNU induced primarily base substitutions. The predominant BCNU-induced mutations were G:C----T:A transversions, which comprised 51% (25 of 49) of the mutations; while G:C----A:T transitions, expected from miscoding of O6-alkylguanine, represented only 16.3% (8 of 49) of the mutants recovered. This result was not anticipated, since Chinese hamster ovary cells are deficient in O6-alkylguanine-DNA alkyltransferase, which should render them especially sensitive to O6 alkylguanine-mediated mutations. It was also notable that two "hotspots" for BCNU induced G:C----T:A transversions were observed, which involved different surrounding DNA sequences but similar helix parameters when analyzed by an application of Calladine's Rules. Possible mechanisms for the observed BCNU induced mutations are presented. PMID- 1511436 TI - Relationship of the queuine content of transfer ribonucleic acids to histopathological grading and survival in human lung cancer. AB - To elucidate the significance of tRNA hypomodified with queuine to the grade of malignancies in human solid tumors, the amount of tRNA having guanosine in place of queuosine was determined in human lung cancer and normal lung tissue, by exchanging the unmodified guanosine residue for [3H]guanine. The reaction is catalyzed by guanine:queuine tRNA transglycosylase. Total tRNA was extracted from 23 different lung cancer specimens and the precursor of isoacceptor tRNA that contains guanine instead of queuine in the first or wobble position of the anticodon [(Q-)tRNA] content was determined. In 12 cases the (Q-)-tRNA was determined in normal lung tissues as well. In each individual, the (Q-)tRNA content in lung cancer tissue was higher than that of the normal lung tissue. The (Q-)tRNA content was not correlated to the surgicopathological staging of the patients but was highly correlated to the histopathological classification of the tumors. The amounts of (Q-)-tRNA were 1.75 +/- 0.67 (SD), 2.36 +/- 0.89, 3.77 +/- 1.39, 5.18 +/- 2.32, and 7.65 +/- 1.34 pmol/A260 in normal, well, moderately, moderately to poorly, and poorly differentiated tumors. The difference from normal to moderately differentiated or less differentiated groups was significant (P less than 0.05). In 10 patients with (Q-)tRNA higher than 3.5 pmol/A260, their cancers relapsed and only 2 were alive after 4 years. In 11 patients with (Q )tRNA less than 3.5 pmol/A260 in their lung cancer tissues, 7 patients were still alive without any evidence of disease, 3 were dead, and 1 had recurrence of disease. These results, taken together with other previous studies, suggest that a decreased queuosine content of tRNA may be a general feature of neoplasms and may be useful for grading malignancy and perhaps also for the prediction of survival in human lung cancer. PMID- 1511437 TI - New S-adenosylmethionine decarboxylase inhibitors with potent antitumor activity. AB - Methylglyoxal bis(guanylhydrazone) (MGBG) has been studied clinically as an antitumor and antileukemic agent and is recognized as a potent but nonspecific inhibitor of the key polyamine biosynthetic enzyme, S-adenosylmethionine decarboxylase (SAMDC). A series of four SAMDC inhibitors with structural features similar to MGBG have been found to have improved potency and specificity toward the target enzyme, SAMDC. Relative to MGBG, the new derivatives were much more effective in inhibiting partially purified preparations of SAMDC (50% inhibitory concentration, 10 to 100 nM), much less effective at inhibiting diamine oxidase, and inactive toward ornithine decarboxylase. The inhibitors varied relative to MGBG in their ability to compete with spermidine for uptake, with two being similar and two being less effective. Against L1210 leukemic cells and T24 bladder carcinoma cells, the compounds were slightly less effective than MGBG at inhibiting cell growth, with 50% inhibitory concentration values of 1 to 10 microM as compared with 0.5 and 1.1 microM, respectively, for MGBG. Under 50% growth-inhibitory conditions, the inhibitors decreased SAMDC activity, increased ornithine decarboxylase activity and putrescine pools, and markedly depleted spermidine and spermine pools of L1210 cells. At the same time, mitochondrial integrity as assessed by whole-cell pyruvate oxidation and mitochondrial DNA content was not affected as it was with MGBG. At doses less than one tenth that of the maximally tolerated dose, all of the new inhibitors strongly suppressed the growth of B16 melanoma in vivo with minimal weight loss or toxicity. At doses less than one sixth the maximally tolerated dose, they effectively inhibited the growth of T24 human bladder carcinoma xenografts. In these same systems, MGBG showed only marginal antitumor activity. These studies identify two potent and efficacious inhibitors of SAMDC as potential antitumor agents and reaffirm the importance of SAMDC as a target in anticancer drug discovery. PMID- 1511439 TI - Mucins bearing the cancer-associated sialosyl-Tn antigen mediate inhibition of natural killer cell cytotoxicity. AB - The sialosyl-Tn (STn) antigen is a mucin-associated carbohydrate antigen expressed by a variety of adenocarcinomas. In the colon, expression of this antigen has been associated with a poor prognosis, independent of tumor stage or histology. The present study was performed to determine whether this adverse clinical outcome might be due to an interaction between STn-positive mucin and natural killer (NK) cell cytotoxicity. Ovine submaxillary mucin (OSM), a mucin highly rich in STn antigen, partially inhibited NK cell cytotoxicity against K562 target cells, but only at high concentrations. Low concentrations of OSM were not inhibitory but became markedly inhibitory in the presence of ammonium ions. Two other STn-positive submaxillary mucins also markedly inhibited NK cytotoxicity when combined with ammonium ions. Removal of sialic acid from OSM reversed the OSM/ammonium-mediated inhibition of NK cell activity. Unlike the submaxillary mucins, two mucins derived from human breast and lung cancer cells which lack the STn antigen, did not inhibit NK cell activity in this system. Likewise, four other non-mucin glycoproteins which lack STn expression did not inhibit NK cells despite having levels of sialic acid that were, in some cases, comparable to submaxillary mucin. These results indicate that mucins bearing the cancer associated STn antigen can effectively inhibit NK cell cytotoxicity in the presence of ammonium ions. While this NK cell inhibition is likely to be caused by ammonium, mucin markedly enhances this effect, thereby implicating a novel immunomodulatory property of mucin. PMID- 1511438 TI - Comparisons between two monoclonal antibodies that bind to the same antigen but have differing affinities: uptake kinetics and 125I-antibody therapy efficacy in multicell spheroids. AB - It has been predicted that low affinity antibodies (Abs) should penetrate into tumors more readily than high affinity Abs. However, the absolute uptake and residence time of a high affinity Ab may be better. It is, therefore, not clear whether a high affinity Ab would have a therapeutic advantage. This is particularly relevant with 125I radioimmunotherapy, where targeting of every cell is important. This study compared the uptake kinetics and toxicity in multicell spheroids of two murine monoclonal Abs labeled with 125I. 17-1A was produced by immunization with a human colon cancer cell line and has an affinity of 5.15 x 10(7) M-1. 323/A3 was produced by immunization with a human breast cancer cell line and has an affinity of 1.87 x 10(9) M-1. Binding of both Abs to LS174T spheroids was similar at 4 degrees C, but binding of 17-1A was 8-10-fold less than that of 323/A3 at 37 degrees C. Despite this difference, the toxicity of 125I-17-1A in spheroids after 7 days of incubation was similar to that of 125I 323/A3. Autoradiography showed that 17-1A penetrated the spheroids much more deeply and evenly than did 323/A3. It appears that much of the radiation dose to spheroids treated with 125I-323/A3 was wasted because of the uneven Ab distribution. This study demonstrates the potential advantage of using Abs of lower affinity for 125I radioimmunotherapy, because of their more even distribution. It also suggests that a large number of binding sites per cell may be a disadvantage if more 125I is bound than is necessary to kill the cell, because this may slow Ab penetration. PMID- 1511440 TI - GGT to GTT transversions in codon 12 of the K-ras oncogene in rat renal sarcomas induced with nickel subsulfide or nickel subsulfide/iron are consistent with oxidative damage to DNA. AB - Nickel is a toxic, mutagenic, and carcinogenic metal of significant occupational and environmental concern. Although several cellular targets of nickel have been identified, considerable evidence suggests that it can act indirectly upon DNA by inducing the formation of oxidized purines or pyrimidines that constitute promutagenic lesions. In this study, we examined nickel subsulfide (Ni3S2)- or Ni3S2/iron-induced renal sarcomas in F344 rats for the presence of transforming mutations in the K-ras oncogene. Selective oligonucleotide hybridization analysis of K-ras gene sequences amplified by polymerase chain reaction revealed that 1 of 12 primary tumors induced with Ni3S2 and 7 of 9 primary tumors induced with Ni3S2/iron contained exclusively GGT to GTT activating mutations in codon 12. These mutations are consistent with the known ability of nickel, in the presence of an oxidizing agent, to catalyze formation of 8-hydroxydeoxyguanosine, which in turn promotes misincorporation of dATP opposite the oxidized guanine residue. The presence of GGT to GTT transversions was confirmed by direct sequencing of the polymerase chain reaction products. Sequencing also revealed that there were no transforming mutations in codons 13 or 59-61. Additionally, a direct correlation between shortened tumor latency and the presence of activating ras mutations was noted. These results show that, in rat kidney, Ni3S2 can induce transforming mutations that are consistent with the ability of nickel to produce oxidative lesions and that iron, which exacerbates the extent of cellular oxidative damage, can enhance the frequency of these transforming mutations. PMID- 1511441 TI - Characterization of a complementary DNA for rat liver aryl sulfotransferase IV and use in evaluating the hepatic gene transcript levels of rats at various stages of 2-acetylaminofluorene-induced hepatocarcinogenesis. AB - A complementary DNA (cDNA) for rat hepatic aryl sulfotransferase IV (AST IV) was isolated, characterized, and used as a hybridization probe to evaluate the molecular basis for the differential expression of AST IV during 2 acetylaminofluorine (2AAF)-induced hepatocarcinogensis. The AST IV cDNA clone was obtained by immunochemical screening of a male Sprague-Dawley rat liver cDNA library. The AST IV cDNA was found to be 1.3 kilobases long and to encode a fusion protein which was reactive with an antibody to AST IV and enzymatically able to generate the sulfuric acid ester of N-hydroxy-2AAF. Sequence analysis of the AST IV cDNA showed it to be 1127 residues in length and to have essentially complete homology with PST-I cDNA, a previously reported (S. Ozawa, et al., Nucleic Acids Res., 18: 4001, 1990), 1028-base cDNA for an uncharacterized rat liver aryl sulfotransferase. Comparison of the PST-I/AST IV cDNA-deduced amino acid sequence with data from a partial (51%) amino acid sequence analysis of purified AST IV showed complete amino acid homology, confirming the identity of the cDNA and establishing that AST IV was an N-blocked, 291-amino acid protein with a molecular mass of 33,909 daltons. The AST IV cDNA sequence differed from the PST-I cDNA in two principal ways: the 5' end lacked 18 coding bases, and the 3' end contained a 190-base extention in the untranslated region, including a consensus sequence for signalling polyadenylation. Studies of AST IV gene transcript levels showed that the livers of rats fed 2AAF for 3 wk (early stage hepatocarcinogenesis) and hyperplastic nodules from the livers of rats fed 2AAF for 19 wk (intermediate stage hepatocarcinogenesis) displayed transcript levels similar to those of livers from normal rats. This contrasted with the 60 to 70% lower than normal capacity of the mRNA fractions to express AST IV observed during in vitro translation. These results indicated that modulation of AST IV expression at early and intermediate stages of hepatocarcinogenesis involved regulatory mechanisms at the translational level. In contrast, mRNA fractions isolated from some 2AAF-induced liver tumors or from known chemical carcinogen derived rat hepatoma cell lines showed losses of both AST IV transcript level and in vitro translation capacity, suggesting that regulation at the transcriptional level may become important at late stages of 2AAF-induced hepatocarcinogenesis. These results indicated that the molecular mechanisms for the 2AAF-mediated down regulation of AST IV expression during 2AAF-induced hepatocarcinogenesis involved alterations in regulation at both translational and transcriptional levels. PMID- 1511442 TI - Absence of p53 gene mutations in primary nasopharyngeal carcinomas. AB - Alterations in the p53 tumor suppressor gene and Epstein-Barr virus status were investigated in 15 nasopharyngeal carcinoma (NPC) biopsies, 4 xenografts, and 2 cell lines from the Cantonese region of southern China. One other established NPC cell line obtained from a northern Chinese patient was also studied. Restriction fragment length polymorphism analysis revealed a loss of heterozygosity for chromosome 17p, where the p53 gene resides, in only one of 15 NPC biopsies. Polymerase chain reaction-single-stranded conformational polymorphism analysis and direct sequencing failed to detect sequence alterations in exons 5 through 8 of the p53 gene in the 15 tumors and in the 4 NPC xenografts, all of which tested positive for Epstein-Barr virus. In contrast, the 3 NPC cell lines were all negative for Epstein-Barr virus and contained G----C transversions in the p53 gene, with cell lines CNE-1 and CNE-2 harboring identical AGA (arginine) to ACA (threonine) changes at codon 280. These results suggest that p53 inactivation is not a necessary component of nasopharyngeal carcinogenesis in Cantonese but may be important in the establishment of cell lines derived from these tumors. PMID- 1511443 TI - Nonrandom abnormalities involving chromosome 1 and Harvey-ras-1 alleles in rat mammary tumor progression. AB - Little is known about the role of chromosomal abnormalities in the widely used models of rat mammary carcinogenesis. In this study, we cytogenetically analyzed nitrosomethylurea-induced rat mammary adenocarcinomas at different time points of development. As tools to study more advanced stages of malignant progression, we also analyzed the cytogenetic progression of tumors transplanted into younger syngeneic hosts, and of tumors that did not regress or that developed after host ovariectomy. Our results indicate that rat mammary adenocarcinomas appear to start development as diploid lesions with cytogenetically "normal" karyotypes. However, upon progression, tumors showed coexistence of normal diploid clones with abnormal clones bearing specific abnormalities affecting mainly chromosomes 1 and 15. Almost every ovary-independent tumor presented stem lines with specific nonrandom chromosomal abnormalities. Numerical chromosomal abnormalities such as specific trisomies started to develop mainly after subsequent in vivo transplantations. The abnormalities affecting chromosome 1 observed in many tumors were: (a) interstitial deletions and breakpoints for translocation in region 1q22; and (b) partial or complete overrepresentation of chromosome 1 in the form of direct duplication of region 1q22q43 or as trisomy 1. Interestingly, Harvey-ras-1 gene maps to rat chromosome 1, and by Southern analysis we observed that 4 of 8 primary tumors and 6 of 9 ovary-independent tumors showed considerable loss of Harvey-ras-1 signal indicating probable allele loss. However, analyses of some tumor transplants in more advanced stages of progression showed, paradoxically, an increased copy number of the Harvey-ras-1 oncogene coinciding with the presence of the direct duplication observed in chromosome 1 or with trisomy 1 as possible mechanisms for gene amplification. Interestingly, rat chromosome 1 is the homologue to human chromosome 11, and in numerous cases of human breast cancer loss of heterozygosity of several genes in chromosome 11p15.5 has been reported. Some of the rat chromosome 1 abnormalities observed may be equivalent to those affecting 11p15 in human tumors. We also observed 8 tumors with abnormalities affecting chromosome 15. At least 3 genes of interest in breast cancer have been previously mapped to that rat chromosome. The similarities observed with human breast cancer may point to common mechanisms of tumor progression in both species. PMID- 1511444 TI - Selenite cytotoxicity in drug resistant and nonresistant human ovarian tumor cells. AB - Our previous studies on selenite cytotoxicity led us to hypothesize that drug resistant tumor cells with high intracellular glutathione will exhibit a high degree of sensitivity to selenite. To examine this we studied the effects of selenite on drug resistant human ovarian tumor (NIH:OVCAR-3) cells in three assays of cytotoxicity: proliferation; cell viability (trypan blue exclusion); and attachment to a solid matrix. The cells were sensitive to low levels of selenite: concentrations as low as 5 microM inhibited cell proliferation and attachment; and viability was decreased by concentrations as low as 20 microM. In each of these assays the NIH:OVCAR-3 cells were more sensitive to selenite than were drug sensitive human ovarian tumor (A2780) cells. These results suggest the potential for the utilization of selenite in the treatment of some drug resistant tumors. PMID- 1511445 TI - Antibody-mediated specific binding and cytotoxicity of liposome-entrapped doxorubicin to lung cancer cells in vitro. AB - Liposome entrapment of doxorubicin has been shown to reduce its cardiotoxicity in vivo and increase its therapeutic index. A further improvement in therapeutic index could be achieved through targeting of liposome-entrapped drug selectively to cancer cells. Monoclonal antibodies against the squamous lung cancer cell line KLN-205 have been ligated to the surface of long-circulating (Stealth) and conventional liposomes. The antibody-bearing liposomes showed specific, competitive uptake by KLN-205 cells as compared to liposomes bearing nonspecific isotype-matched antibodies or antibody-free liposomes. Doxorubicin-containing antibody-liposomes resulted in as much as a 15-fold decrease in the 50% inhibitory concentration for doxorubicin against KLN-205 cells as compared to free doxorubicin or doxorubicin entrapped in antibody-free liposomes. PMID- 1511446 TI - Platelet-derived growth factor-induced transcription of the vascular endothelial growth factor gene is mediated by protein kinase C. AB - Platelet-derived growth factor and phorbol ester cause an increase in vascular endothelial growth factor (VEGF) mRNA expression in control NIH 3T3 fibroblasts and NIH 3T3 fibroblasts overexpressing human protein kinase C (PKC) alpha. In the case of phorbol ester-induced VEGF expression, the VEGF mRNA levels were significantly higher in cells overexpressing human PKC alpha as compared to control cells. In cells stimulated with platelet-derived growth factor or phorbol ester, induction of expression was lost after down-regulation of PKC. This indicates that PKC is involved in the signal transduction leading to VEGF expression. PMID- 1511447 TI - DNA polymerase beta mutations in human colorectal cancer. AB - Increasing numbers of alterations have been found in protooncogenes (e.g., ras, myc), as well as tumor suppressor genes (e.g., p53, Rb) in various types of tumors. The multiple mutations cannot be explained by the spontaneous mutation rate. It has been suggested that mutator phenotypes leading to the accumulation of these mutations may be required in the early stages of tumorigenesis. To test this hypothesis, the entire coding region of DNA polymerase beta, a repair enzyme, mRNA from colorectal tumors, and corresponding normal mucosa were amplified by polymerase chain reaction, cloned, and sequenced. Mutations in the catalytic domain of DNA polymerase beta were detected in colorectal tumor specimens compared to the normal colorectal mucosa, placenta, and blood samples. Since these mutations changed the structure of polymerase beta, it is expected that the efficiency of the DNA repair system would be impaired and thus may account for the high mutation rate observed in colorectal carcinomas. PMID- 1511448 TI - Multistage carcinogenesis: the Twenty-Second International Symposium of the Princess Takamatsu Cancer Research Fund. PMID- 1511449 TI - 1H- and 13C-NMR studies of solutions of hyaluronic acid esters and salts in methyl sulfoxide: comparison of hydrogen-bond patterns and conformational behaviour. AB - The 1H- and 13C-NMR spectra of the ethyl and benzyl esters and the tetrabutylammonium and tetraethylammonium salts of hyaluronic acid [[symbol: see text]2)-beta-D-GcpA+-1----3)-beta-D-GlcpNAc-(1[symbol: see text]n] in Me2SO-d6 have been assigned using 1D and 2D techniques. The chemical shifts of the resonance of GlcNAc C-3 suggest that the relative orientations of the monosaccharides at the (1----3) linkage in the esters and salts are different. Small differences in the chemical shifts of the resonance GlcA C-4 suggest only a slight conformational variation around the (1----4) linkage. The 13C-NMR data also suggest similarities in conformation between the esters in Me2SO-d6 and the salts in water. The chemical shifts of the 1H resonances for NH and OH groups and their temperature dependence for the esters and salts in Me2SO reveal markedly stronger inter-residue hydrogen bonds between the carboxyl and NH groups and between HO-4 of GlcA and O-5 of GlcNAc for the salts. The 3J2,NH values indicate a slightly different orientation for the acetamido group. For solutions in Me2SO, the higher segmental flexibility of the esters is supported by the line widths, whereas the reduced viscosity for the tetrabutylammonium salt showed a sigmoidal concentration dependence and suggests association of chains which could contribute to the segmental rigidity. The linear concentration dependence for the benzyl ester suggests a higher overall flexibility without chain association. PMID- 1511450 TI - Synthesis of omega-(methoxycarbonyl)alkyl and 9-(methoxycarbonyl)-3,6-dioxanonyl glycopyranosides for the preparation of carbohydrate-protein conjugates. AB - omega-(Methoxycarbonyl)alkyl glycopyranosides of D-mannose having C4, C7, C9, C12, and C15 carbon chains, L-fucose and 2-acetamido-2-deoxy-D-mannose having C7 and C9 carbon chains, D-xylose and 2-acetamido-2-deoxy-L-fucose having a C9 carbon chain, and 9-(methoxycarbonyl)-3,6-dioxanonyl glycopyranosides of D mannose, 2-acetamido-2-deoxy-D-mannose, and L-fucose were synthesized as intermediates for coupling to human serum albumin in order to examine the effect of chain length and hydrophobicity of the spacer arm on the binding specificity of lectins. 8-(Methoxycarbonyl)octyl glycosides of beta-D-Man-(1----2)-alpha-D Man, alpha-D-Man-(1----2)-alpha-D-Man, alpha-D-ManNAc-(1----2)-alpha-D-Man, beta D-GlcNAc-(1----2)-alpha-D-Man, and their 6-O-positional isomers, beta-D-Man-(1--- 6)-alpha-D-Man, alpha-D-Man-(1----6)-alpha-D-Man, alpha-D-ManNAc-(1----6)-alpha-D Man, and beta-D-GlcNAc-(1----6)-alpha-D-Man, were also synthesized. PMID- 1511451 TI - An assay for oligo-(1----4)----(1----4)-glucantransferase activity in the glycogen debranching enzyme system by using HPLC with a pulsed amperometric detector. PMID- 1511452 TI - Synthesis of oligosaccharide inhibitors of neural cell division. PMID- 1511453 TI - Some derivatives of 6-amino-6-deoxy-D-gluconic acid that are precursors for the synthesis of polyamides. PMID- 1511454 TI - A 1H-NMR and MD study of intramolecular hydrogen bonds in methyl beta cellobioside. AB - The existence of an HO-3...O-5' intramolecular hydrogen bond in methyl beta cellobioside in solution in Me2SO-d6 and H2O-CD3OD (4:1 w/w) was studied by 500 MHz 1H-NMR spectroscopy and MD simulations. Temperature coefficients for the chemical shift of the hydroxyl resonances in these solvents were determined and the rates of proton exchange in the latter solvent were obtained from NOE data. With H2O-CD3OD as the solvent, the HO-3...O-5' hydrogen bond was insignificant, but its presence in Me2SO-d6 was confirmed. PMID- 1511455 TI - A precursor to the beta-pyranosides of 3-amino-3,6-dideoxy-D-mannose (mycosamine). AB - SN2-type reaction of 3-O-(1-imidazyl)sulfonyl-1,2:5,6-di-O-isopropylidene-alpha-D gluco furanose with benzoate gave the 3-O-benzoyl-alpha-D-allo derivative 2, which was hydrolysed to give the 5,6-diol 3. Compound 3 was converted into the 6 deoxy-6-iodo derivative 4 which was reduced with tributylstannane, and then position 5 was protected by benzyloxymethylation, to give 3-O-benzoyl-5-O benzyloxymethyl-6-deoxy-1,2-O-isopropylidene-alpha -D- allofuranose (6). Debenzoylation of 6 gave 7, (1-imidazyl)sulfonylation gave 8, and azide displacement gave 3-azido-5-O-benzyloxymethyl-3,6-dideoxy- 1,2-O-isopropylidene alpha-D-glucofuranose (9, 85%). Acetolysis of 9 gave 1,2,4-tri-O-acetyl-3-azido 3,6-dideoxy-alpha,beta-D-glucopyranose (10 and 11). Selective hydrolysis of AcO-1 in the mixture of 10 and 11 with hydrazine acetate (----12), followed by conversion into the pyranosyl chloride 13, treatment with N,N-dimethylformamide dimethyl acetal in the presence of tetrabutylammonium bromide, and benzylation gave 3-azido-4-O-benzyl-3,6-dideoxy-1,2-O-(1-methoxyethylidene)-alpha-D glucopyranose (15). Treatment of 15 with dry acetic acid gave 1,2-di-O-acetyl-3 azido-4-O-benzyl-3,6-dideoxy-beta-D-glucopyranose (16, 86% yield) that was an excellent glycosyl donor in the presence of trimethylsilyl triflate, allowing the synthesis of cyclohexyl 2-O-acetyl-3-azido-4-O-benzyl-3,6-dideoxy-beta-D glucopyranoside (17, 90%).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1511456 TI - Study on fluorination of 2,3-dideoxy-2,3-(N-tosylepimino)-alpha-D allopyranosides, and synthesis of 3'-deoxy-3'-fluorokanamycin B and 3',4'-dideoxy 3'-fluorokanamycin B. AB - Reaction of the structurally rigid methyl 2,3-dideoxy-4,6-O-isopropylidene-2,3-(N tosylepimino)-alpha-D-a llopyranoside (6) with KHF2 in DMF at 150 degrees gave initially methyl 2,3-dideoxy-2-fluoro-4,6-O-isopropylidene-3-tosylamido-alpha-D altrop yranoside (10) by N-tosylepimine-ring opening, and 10 was gradually converted into the stable methyl 2,3-dideoxy-3-fluoro-4,6-O-isopropylidene-2 tosylamido-alpha-D-glucopyra noside (11). A reversible mechanism involving 6 and 10 has been proposed. In the mobile methyl 2,3-dideoxy-2,3-(N-tosylepimino)-alpha D-allopyranoside (7) and the corresponding 4,6-di-O-acetyl (8) and -di-O-methyl derivatives (9), reactions with KHF2 proceeded comparatively rapidly giving the corresponding 3-deoxy-3-fluoro-alpha-D-glucopyranosides as the major products. A slightly different reaction mechanism for the mobile compounds has been proposed. By application of this study, 3'-deoxy-3'-fluorokanamycin B was prepared by treatment of 4",6"-O-cyclohexylidene-2'-deamino-3'-deoxy-3'-epi-6'-N methoxycarbonyl- 1,3, 3"-tri-N-tosyl-2',3'-(N-tosylepimino)kanamycin B (21) with KHF2 as the key reaction. 3',4'-Dideoxy-3'-fluorokanamycin B was also prepared. Both compounds were active against resistant bacteria producing 3'-modifying enzymes. PMID- 1511457 TI - Additive effects of antitumor drugs and lymphokine-activated killer cell cytotoxic activity in tumor cell killing determined by lactate-dehydrogenase release assay. AB - The effect of pretreatment with antitumor drugs on lymphokine-activated killer (LAK) cell cytotoxic activity, determined by lactate-dehydrogenase(LDH)-release assay, was investigated. LAK cells were induced by incubating peripheral blood lymphocytes of healthy donors in medium containing interleukin-2 (IL-2) and monoclonal anti-CD3 antibody for 6-7 days. A human lung squamous carcinoma cell line, SQ-5, was used as an adherent target. After 24 h exposure of the target cells to cisplatin, doxorubicin, or mitomycin C, the drugs were washed off and LAK cells were added at an E/T ratio of 5. During further incubation for 48 h, LDH release from cisplatin- or doxorubicin-pretreated target cells was markedly higher than that from non-pretreated target cells. The combination of cisplatin and LAK cells has an additive cytotoxic effect and that of mitomycin C and LAK cells does not; there may also be an additive effect late in the toxicity mechanism between doxorubicin and LAK cells. PMID- 1511458 TI - Growth of MCF-7 human breast carcinoma in severe combined immunodeficient mice: growth suppression by recombinant interleukin-2 treatment and role of lymphokine activated killer cells. AB - The severe combined immunodeficient (SCID) mouse, lacking functional T and B lymphocytes, has been considered by many groups to be a prime candidate for the reconstitution of a human immune system in a laboratory animal. In addition, this immuno-deficient animal would appear to have excellent potential as a host for transplanted human cancers, thus providing an exceptional opportunity for the study of interactions between the human immune system and human cancer in a laboratory animal. However, because this animal model is very recent, few studies have been reported documenting the capability of these mice to accept human cancers, and whether or not the residual immune cells in these mice (e.g. natural killer, NK, cells; macrophages) possess antitumor activities toward human cancers. Thus, the purpose of this study was (a) to determine whether or not a human breast carcinoma cell line (MCF-7) can be successfully transplanted to SCID mice, (b) to determine whether or not chronic treatment of SCID mice with a potent lymphokine (recombinant interleukin-2, rIL-2) could alter MCF-7 carcinoma growth, and (c) to assess whether or not rIL-2-activated NK cells (LAK cells) are important modulators of growth of MCF-7 cells in SCID mice. To fulfill these objectives, female SCID mice were implanted s.c. with MCF-7 cells (5 x 10(6) cells/mouse) at 6 weeks of age. Six weeks later, some of the mice were injected i.p. twice weekly with rIL-2 (1 x 10(4) U mouse-1 injection-1). Results clearly show that MCF-7 cells can grow progressively in SCID mice; 100% of the SCID mice implanted with MCF-7 cells developed palpable measurable tumors within 5-6 weeks after tumor cell inoculation. In addition, MCF-7 tumor growth was significantly (P less than 0.01) suppressed by rIL-2 treatment. rIL-2 treatment was non-toxic and no effect of treatment on body weight gains was observed. For non-tumor bearing SCID mice, splenocytes treated in vitro with rIL-2 (lymphokine-activated killer, LAK, cells) or splenocytes derived from rIL-2-treated SCID mice (LAK cells) had significant (P less than 0.01) cytolytic activity toward MCF-7 carcinoma cells in vitro. In contrast, splenocytes (LAK cells) derived from tumor(MCF-7)-bearing rIL-2-treated SCID mice lacked cytolytic activities toward MCF-7 cells in vitro. No significant concentration of LAK cells in MCF-7 human breast carcinomas ws observed nor did rIL-2 treatment significantly alter growth of MCF-7 cells in vitro.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1511459 TI - Correlation of eosinophilia with clinical response in patients with advanced carcinoma treated with low-dose recombinant interleukin-2 and mitomycin C. AB - On the basis of our clinical findings that the ability of cancer patients to generate lymphokine-activated killer cells became markedly augmented after mitomycin C administration, we designed a treatment regimen comprising mitomycin C 12 mg/m2, i.v. on day 1 and recombinant interleukin-2 700 U/m2 (8000 IU/kg), i.v. every 12 h from day 4 through day 8. The treatment course was repeated at almost 7-day intervals. Altogether 33 patients with advanced carcinoma, including mainly gastrointestinal carcinoma, were treated with this regimen. Of these, 10 had a partial response (PR) and 4 had a minor response (MR). Since eosinophil counts peaked 1 day after either the first or second course of the therapy, the posttreatment values were compared to each pretreatment level, with regard to the clinical antitumor response to this treatment. When patients who showed PR were defined as responders, absolute eosinophil counts and the percentage of eosinophils in responders after both the first and second courses of the therapy were significantly greater than each pretreatment value or the posttreatment level in nonresponders. Further, these findings were almost identical, when both PR and MR were considered to be a true remission and therefore patients who exhibited PR or MR were defined as responders, although the difference between posttreatment levels of eosinophils in responders and nonresponders was not significant at the second course. These results indicate that eosinophilia induced by this treatment correlates with the clinical response to this therapy. PMID- 1511460 TI - Effects of tumor necrosis factor alpha, interferon alpha and interferon gamma on non-lymphoid leukemia cell lines: growth inhibition, differentiation induction and drug sensitivity modulation. AB - The potential role of tumor necrosis factor alpha (TNF alpha), interferon alpha (IFN alpha) and interferon gamma (IFN gamma) in the therapy of non-lymphoid leukemia was studied in ten non-lymphoid leukemia cell lines. All three cytokines tested inhibited the growth of the cell lines. However, a high degree of variability in susceptibility to cytotoxic/cytostatic effect of the cytokines was found among individual cell lines. Some cell lines were sensitive to the antiproliferative action of only one of the cytokines tested, but were resistant to the others. Combinations of two cytokines had additive or synergistic effects and inhibited cell growth to a greater extent than did the individual cytokines alone. In addition to the growth-inhibitory effect, the cytokines induced an apparent cell differentiation. The differentiation of the two most sensitive cell lines, EoL-1 and PL-21, was confirmed using the nitroblue tetrazolium reduction test, by changes in cell morphology, immunophenotype marker profiles and by changes in c-myb expression. Furthermore, we showed that even in the cell lines relatively resistant to the antiproliferative effect of cytokines, such as cell line KCL-22, the inhibition of cell growth could be markedly increased with the DNA-topoisomerase-II-targeted drug, doxorubicin. Our data thus suggest that TNF alpha, IFN alpha and IFN gamma together have a potential role in the immunotherapy of non-lymphoid leukemia in terms of their antiproliferative action, and their ability to induce differentiation and to modulate drug sensitivity. PMID- 1511461 TI - The augmentation of lymphokine-activated killer activity following pulsing of human peripheral blood mononuclear cells with recombinant human interleukin-2. AB - The short-term exposure of peripheral blood mononuclear cells (PBMC) to recombinant human interleukin-2 (rhIL-2) at 37 degrees C leads to the generation of lymphokine-activated killer (LAK) activity similar in magnitude to that obtained by the exposure of PBMC to rhIL-2 continuously for 3-5 days. In order to investigate whether the required signal for LAK induction occurred during the short exposure to rhIL-2 or at a later point in the induction phase, PBMC were exposed to rhIL-2 for 1 h at 4 degrees C and then exposed to a low-pH wash to remove bound IL-2 from its receptor. PBMC treated in such a way showed increased LAK activity and proliferation compared to cells exposed to rhIL-2 alone. Expression of the p55 (alpha) subunit of the IL-2 receptor was also increased. In order to cause the augmentation, a lowering of the pH below 4.0 was necessary, and exposure of PBMC to low pH alone (in the absence of rhIL-2) failed to cause activation. Another relevant feature was a transient increase in the expression of the p75 subunit of the IL-2 receptor (beta chain) immediately following the exposure to low pH and the release of interferon gamma, tumour necrosis factor alpha and IL-6; activation was blocked by the inclusion of neutralising antisera raised against rhIL-2 and interferon gamma, thus demonstrating that the endogenous release of these cytokines is important for activation. PMID- 1511462 TI - Cellular immunosuppression in children with acute lymphoblastic leukemia: effect of consolidation chemotherapy. AB - The present study was designed to evaluate the chemotherapy-induced cellular immunosuppression in 20 children with acute lymphoblastic leukemia (ALL) in remission and receiving maintenance chemotherapy. Peripheral blood was serially obtained from leukemic children during vincristine/cyclophosphamide/6 mercaptopurine/prednisone combined consolidation chemotherapy. The mean absolute number of peripheral blood lymphocytes as well as the mean absolute numbers of lymphocyte subsets (T cells, T cell subsets, B cells, and natural killer cells) from leukemic children before consolidation chemotherapy were all significantly lower than in control subjects; however, the percentages of lymphocyte subsets were similar in both groups. After consolidation chemotherapy, the percentages of CD4+ T lymphocytes and natural killer (NK) cells were significantly decreased and the percentages of monocytes and CD8+ T lymphocytes were significantly increased. Phytohemagglutinin- and 12-O-tetradecanoylphorbol-13-acetate-induced production of interleukin-2 (IL-2) and NK-cell-mediated cytotoxic activity by peripheral blood mononuclear cells (PBMC) were also substantially decreased in the post therapy groups. NK activity correlated with the percentage of NK cells in PBMC. In contrast, OK432-induced production of tumor necrosis factor alpha (TNF alpha) and killer activity against NK-resistant target cells were significantly increased after therapy as compared with the pre-therapy and control groups. TNF alpha production correlated with the percentage of monocytes in PBMC. These results demonstrate that substantial quantitative and qualitative chemotherapy induced abnormalities of the cellular immune system are present in the majority of patients treated with ALL. It is also suggested that the increased TNF alpha production by monocytes and the appearance of potent killing activity against NK resistant targets might compensate for the defects of IL-2 production and NK activity during intensive consolidation chemotherapy. PMID- 1511464 TI - Recombinant interleukin-2 and interferon alpha immunotherapy following autologous bone marrow transplantation. A case report of cardiovascular toxicity with serial echocardiographic evaluation. AB - The most serious side effects of recombinant interleukin-2 (rIL-2) and recombinant interferon-alpha (rIFN alpha) immunotherapy are cardiovascular disturbances, including systemic hypotension, left-ventricular dysfunction and pulmonary edema. We present a 25-year-old female who developed reversible cardiogenic shock during intermediate dose rIL-2 and low dose rIFN alpha therapy. Rapid clinical improvement occurred after intravenous fluid and dopamine support. A serial echocardiographic evaluation, which has not been described previously in this setting, is reported. PMID- 1511463 TI - Effect of picibanil (OK432) on neutrophil-mediated antitumor activity: implication of monocyte-derived neutrophil-activating factors. AB - Picibanil (OK432), an extract from streptococci, has been widely utilized to treat malignant ascites and pleural effusions. The antitumor mechanism is believed to include complement-mediated neutrophil activation. Employing a flow cytometric analysis of actin polymerization as an indicator of cell activation as well as a tumor proliferation assay, we have found that monocyte-derived neutrophil-activating factors were involved in OK432-induced neutrophil activation as well as antitumor activity. OK432-stimulated (0.1 KE/ml; 0.01 mg/ml) monocyte supernatants (OKMS) induced neutrophil actin polymerization and chemotaxis. OKMS were responsible for neutrophil-mediated inhibition of human leukemic (CEM) cell proliferation and stimulated neutrophils to produce superoxide in the presence of CEM leukemic cells at an effector/target ratio higher than 20/1. In contrast, OK432 alone, OK432-stimulated lymphocyte supernatants, or OK432-stimulated neutrophil supernatants had no effect on neutrophil activation or suppression of tumor cell proliferation. OK432 in combination with mononuclear cells also had no effect on the inhibition of CEM cell proliferation. Pretreatment of OKMS at 56 degrees C for 30 min did not affect its ability to activate neutrophils, implying that complement activation is not responsible for the neutrophil activation. Supernatants from OK432 stimulated mononuclear cells, as determined by enzyme-linked immunosorbent assays and radioimmunoassays, contained high levels of interleukin-8 (IL-8; 1567 +/- 145 pg/ml) and tumor necrosis factor (TNF alpha; 2105 +/- 152 pg/ml), low levels of leukotriene B4 (800 +/- 45 pg/ml) and IL-1 beta (180 +/- 22 pg/ml), but interferon gamma was not detectable. IL-1 beta, IL-8, and TNF alpha transcripts, undetectable in untreated monocytes, increased significantly after 30-60 min exposure to OK432. These results suggest that neutrophil-activating factors from monocytes or resident macrophages may play an important role in the OK432-induced neutrophil activation and antitumor activity. PMID- 1511465 TI - Creatine and cyclocreatine effects on ischemic myocardium: 31P nuclear magnetic resonance evaluation of intact heart. AB - The purpose of this study was to investigate the effects of prior dietary supplementation with creatine (Cr) or cyclocreatine (Cy, a synthetic analogue of Cr) on high energy phosphate metabolism of the ischemic myocardium. To this end, 48 rats were fed the following powdered rat chow diet for 21 days: 16 were fed chow without additives (CON); 16 were fed a diet containing 1% Cr by weight (CR); 16 were fed a diet containing 1% Cy by weight (CY). At the end of the feeding period, rats were anesthetized, hearts harvested and perfused in the Langendorff mode using Krebs-Henseleit buffer (maintained at 37 degrees C, equilibrated with 95% O2/5% CO2) to which 11 mM glucose was added. 31P nuclear magnetic resonance (NMR) studies of myocardial bioenergetics were done using a Bruker AM 500 spectrometer. After acquisition of preischemic spectra, global ischemia was produced by clamping aortic inflow. Ischemia was maintained until adenosine triphosphate (ATP) became NMR invisible (CON = 34 +/- 11 min; CR = 32 +/- 13 min; CY = 56 +/- 13 min; p less than 0.05 CY vs. CR and CON). Half-lives of ATP were 19 min for CON and CR and 37.5 min for CY; half-lives of phosphagen were 4 min for CON and CR and 11 min for CY. Time for return of mechanical function (heart rate x systolic pressure) after ischemia was similar for all three groups (CON = 28 +/- 28, CR = 34 +/- 22, and CY = 22 +/- 15 min), even though the CY group was subjected to longer periods of ischemia). These data indicate that CY, but not CR, pretreatment provides myocardial protection either during and/or after ischemia and allows return of mechanical function after much longer episodes of ischemia than in CON and CR. One factor in the mechanism of protection may be the prolonged maintenance of phosphagen due to the higher equilibrium concentration of phosphocyclocreatine which in turn provides substrate for continued synthesis of ATP during and after ischemia, thus defining Cy as a bioenergetic protective agent. Other mechanisms of protection remain to be defined. PMID- 1511466 TI - Cardiac sympathetic nervous activity during myocardial ischemia, reperfusion and ventricular fibrillation in the dog--effects of intravenous lidocaine. AB - In 12 open-chest dogs, cardiac sympathetic nervous activity (CSNA) was recorded before and after occlusion of the left anterior descending coronary artery as well as during reperfusion and ventricular fibrillation (VF). In 7 control animals, CSNA did not significantly differ from preocclusion levels when determined 20 min after occlusion (+3.5 +/- 1.5%, mean +/- SEM) and up to 15 min following reperfusion (+1.5 +/- 0.6%). However, VF was associated with a potential increase in CSNA by 106 +/- 15.5% (p less than 0.001). The effect of lidocaine (6 mg/kg) on cardiac sympathetic tone was examined in 5 additional animals. Lidocaine reduced control CSNA by 23 +/- 4.7% (p less than 0.001); subsequent ischemia and reperfusion did not substantially change the level of preocclusion activity. CSNA decreased significantly also during VF (52 +/- 4.2%, p less than 0.001). In conclusion, efferent CSNA was slightly altered in the course of acute myocardial ischemia and reperfusion, but significantly increased during VF. Lidocaine produced marked attenuation of CSNA in anesthetized dogs. PMID- 1511467 TI - Arrhythmogenic mechanisms in human atrial and ventricular muscle fibers. AB - Mechanisms which may lead to cardiac arrhythmias were studied in atrial and ventricular tissues from human hearts. In human atrial fibers, diastolic depolarization (DD) was consistently present, but did not induce spontaneous discharge. Epinephrine enhanced DD, could induce delayed afterdepolarizations (DADs) and (in combination with strophanthidin) trigger repetitive activity. The presence of DD modified the recovery of premature action potentials. Human ventricular fibers did not exhibit DD and were more resistant to Ca overload. It is concluded that in atrial tissues the presence of DD may not induce automatic arrhythmias, but it may influence conduction and re-entry rhythms. Cardioactive drugs may induce DADs and repetitive activity in the atria and less easily in the ventricles. The attainment of a threshold may be facilitated when DADs are superimposed. PMID- 1511468 TI - Coronary artery bypass grafting in the elderly--a review of studies on patients older than 64, 69 or 74 years. AB - 21 studies reporting on at least 100 elderly patients were reviewed to assess the influence of patient age on outcome of isolated coronary artery bypass surgery. Elderly patients were variously defined as being older than 64, 69 or 74 years of age. They had significantly higher incidences of female sex, unstable angina, urgent surgery, extensive coronary disease, peripheral vascular disease and other risk factors, but left ventricular function was similar to younger patients. The number of grafts inserted and operation times were also similar. Operative mortality and multiorgan morbidity were significantly higher with advancing age. Late survival and relief of angina were generally good. PMID- 1511469 TI - Percutaneous transluminal coronary angioplasty of oversized saphenous coronary bypass grafts: 'hugging balloons' or single peripheral dilatation catheter technique? AB - The use of angioplasty in patients with previous coronary bypass grafts (CABG) has been described in several reports. CABG diameter often exceeds the size of the available coronary balloon dilatation catheters. Simultaneous inflation of two side-by-side balloons or a peripheral angioplasty catheter have been used to achieve optimal balloon-vessel ratio. We describe our experience with the two balloon technique (case 1) and with a single peripheral angioplasty balloon (case 2) to dilate oversized CABG. PMID- 1511470 TI - Abnormal left ventricular filling pattern in patients with single vessel coronary artery disease: effect of angioplasty. AB - To study the effect of coronary angioplasty (PTCA) on left ventricular (LV) diastolic filling, mitral Doppler flow tracings of 15 patients with isolated stenosis of the left anterior descending coronary artery (LAD) and normal systolic LV function were recorded before PTCA as well as 24 h and 3 months after successful PTCA. Compared to control subjects, patients with LAD stenosis exhibited an abnormal LV filling velocity pattern before PTCA. The day following PTCA, the ratios of the early peak diastolic velocity to the peak late diastolic velocity and of the time velocity integral of the early diastolic filling phase to the time velocity integral of the late diastolic filling phase were unchanged. Despite the absence of clinical evidence of restenosis, LV filling remained abnormal 3 months after PTCA. The results suggest that abnormalities of the LV filling velocity in patients with isolated LAD stenosis and normal systolic function may persist as long as 3 months after PTCA. PMID- 1511471 TI - Prognosis in diabetics with chest pain or other symptoms suggestive of acute myocardial infarction. AB - We evaluated the prognosis of 599 diabetics who came to the emergency department with chest pain or other symptoms suggestive of acute myocardial infarction (AMI). They made up 8% of the patients with such symptoms (n = 7,157). Diabetics had a 1-year mortality rate of 25% as compared with 10% for nondiabetics (p less than 0.001). The difference remained significant regardless of whether there was a strong or a vague initial suspicion of AMI. On admission, independent risk factors for death were age, acute congestive heart failure and initial degree of suspicion of AMI. We conclude that among diabetics who appear in the emergency department with chest pain or other symptoms suggestive of AMI, 25% are dead within 1 year. The prognosis is directly related to the initial suspicion of AMI. PMID- 1511473 TI - Multivariate analysis of the variables affecting left ventricular filling in normal subjects. AB - Pulsed Doppler measurements of left ventricular filling (LVF), two-dimensional and M-mode echocardiograms were performed in 189 healthy subjects, in order to evaluate factors influencing LVF Doppler indexes in normal subjects. LVF Doppler indexes (peak E, peak A, peak E/peak A, deceleration rate of peak E (ED) were related by univariate and multivariate analyses with the following parameters: age, sex, heart rate, systolic and diastolic blood pressure, aortic root and left atrial dimensions, left ventricular mass index, left ventricular shortening fraction. The stepwise analysis showed that age by itself explained up to 18% of peak E variance, 50% of peak A variance, 61% of peak E/peak A variance and 25% of ED variance. The other variables entered into the regression, slightly improved the predictive power (less than 10%). In conclusion, age is the major independent factor affecting LVF in normal subjects, although other variables show significant correlation also after age adjustment. PMID- 1511472 TI - Rapid estimation of left ventricular ejection fraction in acute myocardial infarction by echocardiographic wall motion analysis. AB - Echocardiographic estimates of left ventricular ejection fraction (ECHO-LVEF) in acute myocardial infarction (AMI) were obtained by a new approach, using visual analysis of left ventricular wall motion in a nine-segment model. The method was validated in 41 patients using radionuclide ventriculography (RNV) and contrast ventriculography measurements of LVEF for comparison. ECHO-LVEF from the 41 patients correlated well with the reference methods (y = 1.5x - 14.7, r = 0.93; linear regression analysis; 95% confidence limit for a single determination of ECHO-LVEF was 17.2). Interobserver variability by linear regression was r = 0.89, SEE = 7.1 with a mean difference between paired observations of -1.5 +/- 6.9 (SD). In a random sample of 18 patients (45 observations), ECHO-LVEF allowed separation between RNV-LVEF values greater than or equal to 40 and less than 40, representing low and high risk groups following AMI. Thus, the results showed that simple, readily available wall motion-derived estimates of LVEF were as closely associated with LVEF measured by standard reference methods as were previously published, more cumbersome, planimetric echocardiographic methods. Reporting on global LVEF function in LVEF units rather than in nonstandardized wall motion scores of index values may facilitate intra- and interhospital communication and the use of optimized echocardiographic risk stratification after AMI. PMID- 1511474 TI - Evaluation of the valve area underestimation by the continuity equation. AB - During the last years, noninvasive determination of the aortic valve area by Doppler echocardiography using the continuity equation became popular. However, a systematic valve area underestimation of about 15% compared to invasive measurements using the Gorlin formula has been reported. The cause therefore is unknown. The purpose of this study was to evaluate whether the valve area underestimation by the Doppler method might be due to differences in the hydrodynamic background of both methods. This comparison is facilitated by the fact that the Gorlin formula is based on the continuity equation. Compared to the continuity equation, there are four changes within the Gorlin formula: (1) the additional use of a discharge coefficient, which leads to valve area overestimation by the factor 1.17; (2) neglect of the pre-stenotic velocity, causing further overestimation by the factor 1.036 (in mild stenosis this factor may be 1.18 and more); (3) the wrong calculation of the mean pressure drop, which leads to a mean change by the factor 0.95, and (4) the incorrect substitution of the height by the pressure drop in the derivation of the Gorlin formula causes underestimation by the factor 0.97. Combining these four factors results in valve area overestimation of the Gorlin formula compared to the continuity equation by the factor 1.12. This explains to a large extent the valve area underestimation by the continuity equation. PMID- 1511475 TI - Effects on serum lipids of adding fruits and vegetables to prudent diet in the Indian Experiment of Infarct Survival (IEIS). AB - In a randomized, single-blind and controlled trial, the effects of the administration of fruits and vegetables (mean 582 vs. 188 g/day) for 12 weeks were compared as adjuncts to a prudent diet in the management of 202 group A and 204 group B patients with acute myocardial infarction (AMI). Fruits and vegetables decreased total serum cholesterol level (26.4 vs. 13.8 mg/dl, p less than 0.01) low-density lipoprotein cholesterol (20.0 vs. 9.8 mg/dl, p less than 0.01), triglycerides (20.6 vs. 10.6 mg/dl, p less than 0.01) and fasting blood glucose (22.4 vs. 12.6 mg/dl, p less than 0.01) levels more significant in the intervention group than changes in the control group. Adherence to dietary advice was assessed by questionnaires. Total adherence score in group A was significantly higher than in group B. Group A patients also had a significantly smaller rise in lactate dehydrogenase cardiac enzyme which indicates that the protective effects of such a diet may be observed within 1 week. There was a significantly greater decrease in mean blood pressure in group A than changes in group B. These data suggest that fruits and vegetables, because of their high soluble dietary fibre and possibly high antioxidant contents, may be a useful and safe adjunct to a prudent diet in the treatment of patients with AMI. The use of fruits and vegetables may be preferred over oat bran, psyllium and guar gum because of their high content of vitamins and minerals. PMID- 1511476 TI - Risk factors related to the 7-year prognosis for patients suspected of myocardial infarction with and without confirmed diagnosis. AB - This study prospectively evaluates the long-term prognosis of patients admitted with chest pain under suspicion of acute myocardial infarction (AMI) with and without confirmed diagnosis. All patients below 76 years of age, free of other severe diseases and alive at discharge, who were admitted to a coronary care unit of a well-defined region during 1 year, constituted the study population. In all, 275 patients with and 257 patients without confirmed AMI (non-AMI) were included. During 7 years of follow-up, 122 cardiac events (96 cardiac deaths and 26 nonfatal AMI) occurred in the AMI patients, and 69 (44 cardiac deaths and 25 nonfatal AMI) were observed in the non-AMI patients. Using univariate analysis, the following risk variables were significantly related to an impaired prognosis of non-AMI patients: age, a history of previous AMI, angina pectoris, clinical heart failure, diabetes and ST or T changes in the electrocardiogram (ECG) on admission. By multivariate analysis, the following risk factors contained independent prognostic information for non-AMI patients: (1) a history of angina pectoris and (2) ST and T changes on the ECG on admission. We conclude that a subset of non-AMI patients at high risk for cardiac events even in the long term can be identified from the medical history and the ECG on admission. These patients should be carefully evaluated prior to discharge, whereas patients without signs of ischemic heart disease have an excellent prognosis. PMID- 1511477 TI - Possible role of the heart rate for the ECG amplitude according to the Brody effect of athletes and controls. PMID- 1511478 TI - CIRSE '92: annual meeting of the Cardiovascular and Interventional Radiological Society of Europe. Barcelona, Spain, August 30-September 3, 1992. Abstracts. PMID- 1511479 TI - Monocyte-independent T-cell activation by polyclonal antithymocyte globulins. AB - The in vitro mitogenic properties of polyclonal antithymocyte and antilymphocyte globulins (ATG) on peripheral blood mononuclear cells were investigated. The ATG were mitogenic in a dose-dependent manner with maximal proliferation observed at 250 or 500 micrograms/ml. ATG activated blastogenesis of CD4+, CD8+, and CD57+ (NK cells) lymphocytes. The ATG induced interleukin-2 (IL-2) and interferon-gamma (IFN-gamma) gene expression and lymphokine secretion in cell culture supernatant and IL-2 receptor (CD25) expression. At submitogenic concentrations ATG potentialized the effect of phorbol esters on T cell proliferation, but not that of calcium ionophore. The mitogenic effect of ATG was not abrogated by monocyte depletion indicating that like CD2 monoclonal antibodies (mAbs) ATG activate T cells via a monocyte-independent pathway. CD3 and CD2 mAbs which activate T cells without binding to B surface determinants stimulated the proliferation of B cells and their differentiation into immunoglobulin (Ig)-secreting cells. In contrast, ATG induced only a transient B cell activation, but failed to support B cell differentiation into Ig-secreting cells despite the secretion of IL-2. These properties shared by ATG obtained in horses or rabbits by immunization with different cell types appear to differ from those of other T cell mitogens. PMID- 1511480 TI - In vitro and in vivo suppression of interleukin-2-activated killer cell activity by chimeric proteins between interleukin-2 and Pseudomonas exotoxin. AB - The biological effects of IL-2 are mediated through high (complex of alpha and beta chain) or intermediate (beta chain) affinity IL-2 receptors. Previously, chimeric proteins composed of IL-2 and Pseudomonas exotoxin (IL-2-PE) were shown to be specifically cytotoxic to cells bearing IL-2 receptors. It has also been shown that IL-2-PE chimeric proteins can abrogate T cell-mediated immune response in vitro. In the current study, we have investigated the effects of IL-2-PE on LAK activity both in vivo and in vitro. We administered either IL-2-PE40 (comprised of IL-2 and 40-kDa portion of PE) or IL-2-PE66 (comprised of IL-2 and 66-kDa molecule of PE) to normal C57BL/6 mice for 3 or 8 days and LAK activity was assessed in various organs of mice. We found that IL-2-PE40 generated LAK activity in various compartments of mice and the level of activity was slightly lower than that observed with an equivalent amount of recombinant (r) IL-2 alone. However, IL-2-PE66 failed to generate LAK activity which would have been induced due to an equivalent concentration of rIL-2. IL-2-PE66 also did not induce LAK activity from the splenocytes during in vitro culture while IL-2-PE40 generated good LAK activity. An equivalent amount of IL-2 also generated potent LAK activity. The suppression of LAK activity by IL-2-PE66 was also evident in cells preactivated with IL-2; however, this inhibition was partial. The suppressive activity of IL-2-PE66 was shown to be mediated through IL-2 receptor interactions as excess amounts of rIL-2 were able to abrogate its effect. Both IL-2 toxins were equivalently cytotoxic to IL-2 receptor-bearing HUT 102 cells and both were able to compete from high and intermediate affinity IL-2 receptors. Taken together, our data indicate that IL-2-PE66 is highly cytotoxic to LAK cells while IL-2-PE40 is less cytotoxic. Thus, data from our study and from other published reports indicate that IL-2-PE66 is more potent immunosuppressive agent than IL-2 PE40. PMID- 1511481 TI - Heat shock induces apoptosis in mouse thymocytes and protects them from glucocorticoid-induced cell death. AB - Thymocyte death is a complex phenomenon under the control of different signals and stimuli. We evaluated the effect of elevated temperature (heat shock, HS) on mouse thymocyte apoptosis. Incubation of thymocytes at 43 degrees C for 20 min induced DNA fragmentation and cell death, but it was also able to decrease the apoptosis induced by dexamethasone (DEX), TPA or Ca2+ ionophore. The anti apoptotic effect was correlated with induction of heat shock proteins (HSPs) and abolished by protein synthesis inhibition. On the other hand, HS-induced unlike DEX-induced apoptosis was not inhibited by protein synthesis and mRNA transcription inhibitors, the PKC inhibitors H-7 and staurosporine, or interleukin-4 (IL-4), but only by Zn2+. These results suggest that HS interferes in thymocyte death by either inducing or inhibiting thymocyte apoptosis and that the induction process mechanisms are different from those of GCH. PMID- 1511482 TI - The developmental patterns of B cell precursors distinguishing between environmental and nonenvironmental forms of phosphocholine. AB - We have analyzed the developmental patterns of two groups of B cell precursors in nonimmunized BALB/c mice with respect to their relative proportions, absolute frequencies, V gene usage, fine specificity, and avidity for antigen. One group of B cells (group I) secretes antibodies specific for PC and PC-containing bacteria, whereas the other group (group II) produces antibodies recognizing only nonenvironmental PC-protein conjugates. A marked shift in the proportions of group I and group II occurs during ontogeny: while the group I B cells dominate (greater than 85%) the adult antibody repertoire, the group II B cells have equal representation in neonatal mice from Days 1 to 7, and remain as a significant portion until 2 weeks of age. Examination of the absolute frequencies of group I and group II B cells revealed that the frequency of group II B cells remained relatively stable throughout ontogeny, whereas group I B cells expanded rapidly after 7 days of age to predominate in the adult. Genetic analysis indicated that early group I antibodies were encoded by VH and VL genes different from adult group I antibodies which are mostly encoded by a single VH (S107) and VL (V kappa 22) gene combination (the T15 idiotype). On the other hand, early group II antibodies used VH genes comparable to their adult counterparts. The majority of early group I antibodies have lower avidity for PC than adult T15+ antibodies, whereas the avidity of neonatal group II antibodies varies considerably and is comparable with that of the adult group II antibodies. Our results suggest that the ontogeny of phosphocholine-specific B cells may be regulated according to their fine specificity rather than to their avidity or V gene usage. PMID- 1511483 TI - Delayed allograft rejection in mice transgenic for a soluble form of the IL-4 receptor. AB - Accumulating evidence suggests that in serum and other biological fluids, cytokine binding is a property associated with soluble proteins, including a high affinity soluble version of the IL-4 receptor (sIL-4R). While it is tempting to speculate that sIL-4R might act as a serum carrier protein or serve to inhibit or modulate IL-4 action, specific biological roles for sIL-4R remain to be established. To further assess the immunoregulatory and therapeutic potential of sIL-4R and other soluble receptors, we have created transgenic mice which constitutively express elevated levels of biologically active sIL-4R. Phenotypic characterization of lymphoid organs in sIL-4R transgenic mice revealed normal numbers of B and T cells and normal surface marker expression. Splenic lymphocytes displayed normal in vitro activities as measured by the PFC response and generation of cytotoxic T cells. In addition, antigen-specific IgE and IgG1 in vivo responses were similar in control and transgenic mice. Despite the apparent developmental normality of the sIL-4R transgenic mice, these animals were markedly deficient in the ability to reject cardiac allografts, suggesting that IL-4 is critical for the generation of alloreactivity. The results further suggest that the ability of sIL-4R to regulate IL-4 activities may be under the control of complex interactions that remain to be elucidated. PMID- 1511484 TI - Monoclonal antibodies specific for novel murine cell surface markers define subpopulations of germinal center cells. AB - A panel of mAbs has been generated which selectively, but not exclusively, recognizes populations of cells within germinal centers of immunized mice. All four mAbs stain B cell populations as defined by flow cytometry. The mAbs FH9.5 and C3.5 also stain T cell subsets (CD4+ and CD8+, respectively). Following density gradient centrifugation of spleen cells from immunized mice the majority of FH9.5+ and C3.5+ B cells are found in the low density, activated fractions. The cells bearing the epitope(s) recognized by the C6C3 and the A6A2 mAbs are less frequent, and from flow cytometric analysis the cells stained with these mAbs are B cells and myeloid cells. The surface markers defined by the four mAbs are not induced following mitogen stimulation of small resting B cells suggesting that these molecules are not general activation markers. Cell lines from a variety of hematopoietic lineages expressing the four markers have been identified. The cell surface molecule immunoprecipitated by the FH9.5 mAb is a polypeptide of 23-28 kDa. The C3.5 antigen is an 85- to 95-kDa protein. These mAbs will be useful in elucidating the complex events involved in B cell differentiation and maturation which occur within germinal centers. PMID- 1511485 TI - The antioxidant activity of ubiquinol-3 in homogeneous solution and in liposomes. AB - With a view to determining the antioxidant effectiveness of ubiquinol, the autoxidation of egg phosphatidylcholine initiated by an azocompound was studied both in homogeneous solution and in liposomes, either in the presence or in the absence of ubiquinol-3. The results show that ubiquinol behaves as a chain breaking antioxidant by trapping lipid peroxyl radicals, its inhibition rate constant being about one half of that of alpha-tocopherol in both systems under investigation. In organic solvents the stoichiometric factor was found approx. 2 and in liposomes approx. 0.5, i.e. one fourth of that of alpha-tocopherol. We suggest that the lower value found in model membranes is due to autoxidation of the quinol itself by a radical chain reaction taking place at the polar interface. Ubiquinol-3 exhibits a sparing effect toward alpha-tocopherol, both in liposomes and in tert-butanol. It is suggested, on a thermodynamic basis, that the regeneration of vitamin E from the corresponding radical is more likely to occur by reaction with the ubisemiquinone rather than with the ubiquinol. Although these results, obtained in in vitro systems, can not be directly extrapolated to an in vivo system, they may be useful to clarify the antioxidant role of ubiquinol in biomembranes. PMID- 1511486 TI - The structure of anhydrous and hydrated dimyristoylphosphatidyl glycerol: a pressure tuning infrared spectroscopic study. AB - The addition of water to anhydrous phospholipids has profound effects on the intermolecular interactions and packing order of phospholipid molecules. These changes, as well as alterations induced by hydration in the orientation of the acyl chains, can be qualitatively assessed using high pressure infrared spectroscopy. Application of this technique to dimyristoylphosphatidyl glycerol (DMPG) showed that hydration causes major changes in (i) the orientation of the carboxyl groups in relation to the glycerol backbone; (ii) the degree of orientational disorder of the acyl chains and (iii) the proximity of neighbouring DMPG molecules. In addition, the frequency of the carbonyl group is shown to be strongly affected not only by changes in the hydrogen bond network, but also by subtle environmental perturbations induced by the conformation of nearby structural units. PMID- 1511487 TI - Thermotropic behavior of fatty acid ethyl esters in phospholipid liposomes. AB - The thermotropic behavior of a series of synthetic fatty acyl ethylesters (FAEE) in multilamellar liposomes has been studied by differential scanning calorimetry and monitoring the changes in polarization emitted by the fluorescent probe 1,6 diphenyl-1,3,5-hexatriene. Their thermotropic behaviour has been compared to that of the homologous fatty acids (FA) from which they are synthesized in vivo in the presence of ethanol. Compared to the correspondent FA, saturated FAEE show, depending on the chain length, a minor rigidifying effect or even a slight fluidizing effect on phospholipid bilayers. Unsaturated FAEE show, compared to the homologous FA, slightly greater fluidizing properties. The difference between FA and FAEE is more evident in single component phospholipid liposomes in the gel phase, and in mixed liposomes of two lipids at temperatures at which microdomains of gel and liquid zones coexist. The calorimetric data suggest that FAEE are completely miscible with phospholipids both in the gel and liquid phases; they appear to destabilize the bilayer wherein the ethoxy head group interferes with the intrinsic phospholipid interactions. PMID- 1511488 TI - Synthesis of biosynthetic inhibitors of the sex pheromone of Spodoptera littoralis. Part II: Acetylenic and cyclopropane fatty acids. AB - The synthesis of new acetylenic and cyclopropane fatty acids, as potential inhibitors of the beta-oxidation step in the proposed biosynthesis of the sex pheromone of the Egyptian armyworm Spodoptera littoralis, is reported. The biological activity of the compounds has been determined by in vitro and in vivo bioassays, and among all the compounds tested, dichlorocyclopropane acid has shown the highest inhibition activity displayed so far. PMID- 1511489 TI - Debenzylation and detritylation by bromodimethylborane: synthesis of mono-acid or mixed-acid 1,2- or 2,3-diacyl-sn-glycerols. AB - A novel method of deprotecting primary alcohols protected with either benzyl or trityl groups by using bromodimethylborane under mild reaction conditions (dichloromethane, -20 to 5 degrees C) has been applied to the synthesis of optically pure mono-acid or mixed-acid 1,2- or 2,3-diacyl-sn-glycerols. This method was particularly useful for the synthesis of long saturated acyl (C12 to C24) as well as unsaturated diacyl-sn-glycerols since little or no acyl migration occurred during deprotection. Diacylation of 3-benzyl-sn-glycerol or 1-benzyl-sn glycerol followed by bromodimethylborane debenzylation gave mono-acid 1,2- or 2,3 diacyl-sn-glycerols, respectively. The mixed-acid 1,2- or 2,3-diacyl-sn-glycerols were prepared from 1-acyl-sn-glycerols or 3-acyl-sn-glycerols, respectively, by tritylation, acylation with a different fatty acid, followed by detritylation with bromodimethylborane. PMID- 1511490 TI - Indole-3-acetic acid-mediated transport of Mn2+ and other ions across phosphatidylinositol vesicular membranes as determined by 31P-NMR. AB - The indolic plant hormone, indole-3-acetic acid (IAA), mediated the transport of Mn2+ and other ions into small unilamellar vesicles prepared from soybean phosphatidylinositol (PI) and this process has been studied using 31P nuclear magnetic resonance spectroscopy (NMR). The rate of Mn2+ movement into PI vesicles is dependent on IAA concentration and temperature with an IAA stoichiometry of 4.1 and an activation energy of 16.8 kcal mol-1 derived for the rate-determining process. These values are altered by low concentrations of endogenous ions (which can be removed by treatment with EDTA) present in the PI. With non-EDTA-treated PI, values of 2.3 and 23.0 kcal mol-1 were obtained for the stoichiometry and activation energy, respectively. These values indicate that (a) IAA interacts with PI membranes; (b) IAA-induced changes in membrane permeability can be substantially modulated by ions and (c) IAA very significantly influences the rate of movement of some (but possibly not all) cations across PI membranes. Such effects are also modified by the oxidation state of the PI. PMID- 1511491 TI - Cation-induced aggregation and fusion of N-acyl-N-methyl-phosphatidylethanolamine vesicles. AB - Aggregation and fusion of unilamellar vesicles consisting of N-acyl-N methylphosphatidylethanolamine were studied as a function of mono- and divalent cation concentrations. The aggregation reactions were irreversible processes, as demonstrated by changes in monovalent ion concentrations and by the addition of ethylenediaminetetraacetic acid (EDTA) to chelate divalent cations, suggesting the possibility of some cation-induced vesicle fusion. An increase in the NaCl ionic strength of the vesicle suspension solutions diminishes the threshold concentration for Li+ and K+ and increases that corresponding to Mn2+, Mg2+ and Ca2+. However NaCl concentrations above 300 mM yield smaller threshold values for the divalent cation-induced processes, probably due to the increased size of phospholipid vesicles as the ionic strength of the medium increases. PMID- 1511492 TI - Stereoselectivity of lipases: esterification reactions of octadecylglycerol. AB - Stereoselectivity of several triacylglycerol lipases (EC 3.1.1.3) has been investigated in the enzymatic esterification of rac-1-O-octadecylglycerol with oleic acid in the presence of organic solvents, such as hexane. X-1(3)-O Octadecylmonooleoylglycerols were the only products formed with most lipases; considerable proportions of X-1(3)-O-octadecyldioleoylglycerols were also formed with the lipase from Candida cylindracea. The mixtures of unesterified enantiomeric substrates, i.e., X-1(3)-O-octadecylglycerols were converted to their 3,5-dinitrophenylurethane derivatives and subsequently resolved into sn-1 and sn-3 enantiomers by HPLC on a chiral stationary phase (Sumichiral OA 2100). The data on enantiomeric excess (ee) and enantiomeric ratio (E) in the unesterified substrate revealed for the lipases from porcine pancreas, Rhizopus sp., Pseudomonas sp., Candida cylindracea, Chromobacterium viscosum and Penicillium cyclopium a distinct preference for 1-O-octadecyl-sn-glycerol over its enantiomer indicating stereoselectivity for the sn-3 position. For the lipase from Rhizomucor miehei a slight stereoselectivity for the sn-1 position was observed. Solvents, such as diethyl ether and dichloromethane, strongly inhibited the esterification reaction, but the enzymatic activity could be restored upon removal of such solvents by washing with hexane indicating reversible inhibition. PMID- 1511493 TI - Rapid synthesis of 2-desoxy-2-amino-3-phosphocholine-glycerinic-acid- alkylester, 1-alkyl-1-desoxy- and 1-O-alkyl-2-desoxy-2-amino-sn-glycero-3- phosphocholines, 3-phospho-N,N'-dimethylethanolamine and -3-phospho-Fmoc- serine-methylester. AB - A convenient sequence for the rapid synthesis of 2-desoxy-2-amino-3 phosphocholine-glycerinic-acid-alkylester , 1-alkyl-1-desoxy- and 1-O-alkyl-2 amino-2-desoxy-3-phospho-derivatives is described. Key steps are the reaction of 1-carbonyloxyalkyl-, 1-alkyl- or 1-O-alkyl-amino-alcohols with phosphorus oxychloride to 1-carbonyloxyalkyl-, 1-alkyl- or 4-substituted 2-chloro-2-oxo 1,3,2-oxazaphospholane followed by nucleophilic displacement with choline tosylate, 1-bromoethane-2-ol or Fmoc-L-serine-methylester and subsequent hydrolysis to 2-amino-lysophospholipids giving the desired compounds in yields ranging between 68% and 81%. Several 2-amino-lysophospholipid analogs can then be prepared by this synthetic scheme utilizing the same oxazaphospholane intermediate. A brief method for the preparation of 2-amino-3-hydroxy-propionic acid-pentyl- and -octylester from L-serine is described, opening a facile access to chiral precursors of phospholipid analogs. PMID- 1511494 TI - Molecular mechanisms of cell motility. PMID- 1511495 TI - Tumor cell adhesion to the extracellular matrix and signal transduction mechanisms implicated in tumor cell motility, invasion and metastasis. AB - The relationship between tumor cell adhesion to the extracellular matrix (ECM) and invasion and metastasis formation is one of the most intensively studied topics in cancer biology within the last 10-15 years. The aberrant molecular relationships between malignant tumor cells and their surrounding ECM have been implicated at virtually every stage of the metastatic process; ranging from steps that involve the local invasion of tumor cells away from the primary tumor to those that are involved in mediating extravasation through microvessel-associated basement membranes at the site(s) of metastasis formation. The complexity of tumor metastasis has required that a reductionist approach be taken in order to identify and relate specific molecular mechanisms involved in tumor cell adhesion to various aspects of tumor metastasis. The intensive research efforts into cell adhesion and tumor cell biology have generated many significant new concepts towards our understanding of the molecular aspects of tumor cell adhesion and metastasis. Our purpose in this article is to briefly summarize the relationship of ECM-stimulated tumor cell adhesion to the processes of tumor cell motility and invasion. This is followed by a discussion of certain aspects of signal transduction pathways that may impact on cell motility, with an emphasis on the relationship between phosphatidylinositol hydrolysis and actin polymerization, as well as certain GTP-binding protein-(G-protein) mediated events that could influence cytoskeletal organization and cell motility. Our emphasis is based on increasing evidence that implicates members of the signal transduction G-proteins in the motility and invasion of many normal and transformed cells. PMID- 1511496 TI - Extracellular matrix contraction by fibroblasts: peptide promoters and second messengers. AB - Cells contracting connective tissue matrices generate tractional forces in tissues. Studies of fibroblast contraction, using collagen gels in an in vitro model, demonstrate that it involves the actin cytoskeleton, specific extracellular matrix receptors and requires stimulation by exogenous promoters. Fibroblast contraction is stimulated by factors released by platelets and potentially secreted within the contracting tissue. Endothelial cells secrete a potent promoter of fibroblast contraction which has been identified as endothelin 1. The pathway through which fibroblast contraction is stimulated appears to require activation of protein kinase C. Tumor cells can also secrete endothelin. These mechanisms may be relevant to tumor progression. PMID- 1511497 TI - Chemotaxis of metastatic tumor cells: clues to mechanisms from the Dictyostelium paradigm. AB - Amoeboid movement, and in some cases, amoeboid chemotaxis, is a key step in tumor metastasis. The high degree of conservation in signal transduction pathways and motile machinery in eukaryotic cells suggests that insights and molecular probes developed from the study of these processes in easily manipulated experimental model systems will be applicable directly to experimentally intractable tumor cells. One such model system, Dictyostelium discoideum, is discussed in terms of the molecular events involved in amoeboid chemotaxis. The application of insights and assays developed with Dictyostelium to early events in the chemotaxis of Lewis lung carcinoma cells is reviewed. PMID- 1511498 TI - Actin structural proteins in cell motility. AB - The machinery for cell locomotion is based in a network of polymerized actin filaments supporting the peripheral cytoplasm. This network or 'gel' consists of actin filaments in a variety of configurations, including cables, loose bundles, and branching arrays; all formed by the interaction of actin-associated proteins with actin filaments. For cell locomotion to occur, this network must be reversibly disassembled or 'solated' to allow protrusion, then re-assembled to stabilize the resulting extension. Thus, proteins to promote both 'solation' and 'gelation' of actin are important for efficient cell locomotion. Because of their distribution, control, and in vitro effects on actin filaments, two such proteins, gelsolin and actin-binding protein (ABP) should play especially important roles in cell motility. Support for this premise is found in in vivo studies of mouse kidney fibroblasts which demonstrated increased translocational locomotion after cytoplasmic gelsolin expression was increased genetically and in melanoma cells missing actin-binding protein which behave as expected for a cell unable to achieve efficient actin gelation. Since malignant transformation is known to affect the expression and distribution of several of these actin structural proteins, including gelsolin, further investigations of the role these proteins play in cell motility will be important to the determination of tumor cell motility and hence metastatic propensity. PMID- 1511500 TI - Inflammatory cytokines stimulate glucose uptake and glycolysis but reduce glucose oxidation in human dermal fibroblasts in vitro. AB - Interleukin-1 alpha (IL-1 alpha) produced alterations in human dermal fibroblast glucose metabolism in vitro of the type seen in severe sepsis in man. Glycolysis and glucose uptake were increased but the oxidation of glucose within the tricarboxylic acid (TCA) cycle was reduced. The combined addition of tumour necrosis factor alpha (TNF alpha) with interferon-gamma (IFN-gamma) similarly increased the dependency for cellular energy provision from an oxidative to the glycolytic state. These cytokine-induced changes in glucose metabolism were unaffected when prostaglandin production was inhibited with a cyclo-oxygenase inhibitor, but were significantly reduced by the steroid dexamethasone. Thus, the inflammatory cytokines IL-1 and TNF alpha reportedly detected in the circulation during severe sepsis may directly affect not only glucose uptake but also its subsequent metabolism within tissue fibroblasts. PMID- 1511499 TI - The role of myosin I and II in cell motility. AB - It has been recognized since the turn of the century that cell motility by non muscle cells requires virtually continuous restructuring of the cytoskeleton (see refs [1-4]). It is also clear that cell motility requires a mechanism for converting chemical energy into mechanical work. The proteins actin and myosin, two important constituents of the cytoskeleton, have been postulated to act as the chemicomechanical transducer in motile cells. Central to their role as a force generating mechanism in motile cells is the ability of myosin (a) to hydrolyze ATP when it interacts with actin and (b) to form filaments. Recent studies on mammalian cells and on the cellular slime mold Dictyostelium discoideum have shed light and at the same time raised questions regarding the involvement of myosin in cell motility. Moreover, they have demonstrated the presence of two types of myosins, called myosin II and myosin I, that have unique biochemical and regulatory properties and that may play different roles in mediating cell motility. In this chapter we will discuss the properties of these two myosins and then describe what is known about their involvement in Dictyostelium and mammalian cell motility. PMID- 1511501 TI - Protein kinase C activity and lipogenesis from glucose in isolated adipocytes of endotoxemic rats. AB - The hypothesis was tested that the insulin-like effects of Gram-negative bacterial endotoxins (ET), exerted after in vivo administration on subsequently isolated adipocytes, might be associated with changes in protein kinase C (PKC) activity. The latter is believed to be involved in insulin's mechanism of action on adipocytes. E. coli ET was administered to rats either as a bolus injection (1 mg/100 g bw, in 160-180 g rats, LD50 for 6 hr) or via subcutaneously implanted osmotic pumps (0.1 mg/100 g bw/24 hr, for 30 hr, in 340-380 g rats). Control animals received sterile saline. At 6 hr after bolus injection, and at 30 hr after the onset of ET infusion, the animals were sacrificed and epididymal adipocytes isolated. PKC activity and intracellular distribution were assayed after partial purification on DE-52 cellulose minicolumns. Lipogenesis was measured by [3-3H]-D-glucose incorporation into triglyceride. ET treatment by either mode induced a significant increase (76-80%) in PKC activity. PKC intracellular distribution was altered only in chronically ET-treated rats and was expressed as an increased enzyme activity in the membrane fraction. The increased PKC activity was associated with elevated rates of insulin-stimulated lipogenesis only in young rats. We conclude that in young rats, whose adipocytes display high rates of lipogenesis along with elevated insulin sensitivity, PKC is likely to be one of the possible factors involved in mediation of insulin-like effects of ET. PMID- 1511502 TI - Intestinal bacterial flora, intestinal pathology, and lipopolysaccharide-induced translocation of intestinal bacteria. AB - The primary aim of this study was to clarify the mechanism and significance of lipopolysaccharide (LPS)-induced translocation of intestinal bacteria. Female Swiss Webster mice were purchased from two different animal suppliers. Twenty four hours following parenteral LPS, mice from both suppliers had noticeable morbidity and mortality. However, intestinal pathology, gram-negative bacterial overgrowth, and increased bacterial translocation was noted in mice purchased from one supplier but not the other. Mice with increased translocation also had overgrowth of cecal gram-negative bacilli, i.e., 10(10) per gram of cecum following parenteral LPS; in contrast, mice without LPS-induced bacterial translocation had 1,000- to 10,000-fold fewer cecal gram-negative bacilli. Additional groups of mice with increased bacterial translocation were also sacrificed two and 6 hr after parenteral LPS; morbidity and intestinal pathology were evident without a corresponding increase in bacterial translocation. Separate groups of these mice were also injected with platelet activating factor, resulting in intestinal pathology similar to that noted with parenteral LPS, but no increase in bacterial translocation. Thus parenteral LPS was consistently associated with morbidity and mortality but not with intestinal pathology, enteric bacterial overgrowth, or increased bacterial translocation. PMID- 1511503 TI - Biological responses to exchange transfusion with liposome-encapsulated hemoglobin. AB - The present study evaluates the biological responses to 10% blood volume infusion ("top-loading," n = 7) or 50% blood volume exchange transfusion (n = 8) with a new preparation of liposome-encapsulated hemoglobin (LEH) in the conscious rat. Top-loading did not affect systemic hemodynamic variables but induced transient thrombocytopenia (-36% +/- 7%; P less than 0.05) and elevation of plasma thromboxane B2 (12.4 +/- 3.8 pg/100 microliters vs. undetectable levels at the control; P less than 0.05). Rats exchanged with LEH maintained mean arterial pressure (MAP) during the 3 hr observation period, whereas control (0.9% NaCl or lactated Ringer's solution) animals developed hypotension (-23 +/- 5 mm Hg, P less than 0.05). The maintenance of MAP in the LEH group resulted from the opposing effects of LEH-induced increase in total peripheral resistance index (TPRI; +0.06 +/- 0.01 mm Hg/ml/min/kg; P less than 0.05), and decreased cardiac index, (Cl, -25 +/- 6 ml/min/kg, P less than 0.05). In contrast, the decline in MAP in the control groups could be attributed to the lower Cl (-65 +/- 8 ml/min/kg; P less than 0.05). All rats developed metabolic acidosis (base excess of -9.7 +/- 0.6 mmol/liter; P less than 0.05), which was transient in the LEH group but progressive in the control groups. These data support the possible use of LEH as a blood substitute when massive transfusions are needed. PMID- 1511504 TI - Altered endothelial mechanisms blunt skeletal muscle microcirculatory responses to live E. coli sepsis in 1K1C hypertension. AB - While renovascular (1K1C) hypertension significantly attenuates small arteriole dilation to sepsis in skeletal muscle of rats, maximal dilation of these small arterioles is not altered in response to an endothelium-independent vasodilator (nitroprusside). This suggests that 1K1C hypertension modifies a receptor-level mechanism to reduce small arteriole vasodilation during sepsis. To test this hypothesis, we used hydroquinone (HQ) to block an endothelium-derived relaxing factor (EDRF) in skeletal muscle arterioles of sodium pentobarbital (45 mg/kg BW) anesthetized 1K1C-renovascular hypertensive male Sprague-Dawley rats which were then made septic. We found that responses of large and small arterioles to sepsis were blunted in hypertensive rats and that these responses were unchanged during the presence of HQ. This suggests 1) that blockade of some vasodilator mechanisms does not unmask an enhanced vasoconstrictor influence during sepsis in 1K1C hypertension and 2) that EDRF mechanisms are blunted by 1K1C hypertension. To further test this second idea, we examined the responses of small arterioles to acetylcholine (ACH) in normotensive and renovascular (1K1C) hypertensive rats before and after EDRF blockade. Skeletal muscle small arterioles were essentially not reactive to ACH in the hypertensives and HQ did not change this response. However, some vasodilation in hypertensives occurred under very high ACH concentrations even during the presence of HQ. These data suggest that sepsis induced small arteriole dilation in skeletal muscle is blunted because endothelium-mediated responses are impaired in renovascular hypertension. Nevertheless, EDRF-independent mechanisms appear to be left intact during this form of hypertension. PMID- 1511505 TI - Effect of ibuprofen upon denervated skeletal muscle resistance and compliance vessels during endotoxemia. AB - The primary aim of these studies was to specifically evaluate the non-neural role of the cyclooxygenase products on the peripheral vascular decompensation associated with endotoxemia. The constant-flow perfused, vascularly isolated, denervated double-canine gracilis muscle preparation in which one muscle is used as a control for the contralateral side was employed. The experimental muscle (GMi) received ibuprofen while the control (GMc) was infused with the vehicle. The results of these studies suggest that endotoxin increases the arterial conductance (i.e., arterial dilation) by 100% and venous compliance (i.e., venoconstriction) by 40%. These observations, which are consistent with venous pooling, were not significantly altered by the continuous intra-arterial infusion of ibuprofen at a peripheral blood concentration of 160 microM. Ibuprofen caused a small but statistically significant increase in the conductance/compliance ratio at 60, 75, and 90 min post endotoxin, suggesting that cyclooxygenase products may play a minor role in the non-neural regulation of capillary fluid dynamics during endotoxemia. Consequently, these studies do not provide convincing evidence that would support a non-neural cyclooxygenase role in the peripheral vascular decompensation reported to occur during systemic endotoxemia. PMID- 1511506 TI - Methylprednisolone improves pulmonary function and hemodynamics in experimental gram-positive septicemia. AB - It has been suggested that the effects of high-dose corticosteroid therapy (HDC) in gram-positive (G+) and gram-negative (G-) septicemia differ. As few data are available on HDC in G+ septicemia, pulmonary and cardiovascular function was studied for 44 hr in five anesthetized pigs subjected to brief infusion of live Staphylococcus aureus (approximately 10(11) cfu) followed by intravenous methylprednisolone (MP, 30 mg/kg) administered as a bolus every 8 hr. Comparisons were made with six septic pigs given no MP but otherwise identically managed. Six control pigs received no bacteria or MP. Infusion of bacteria induced identical transient pulmonary hypertension in both septic groups (52 +/- 7 mm Hg, mean +/- SD), but MPAP remained significantly lower in the pigs with MP (18 +/- 1 mm Hg vs. 30 +/- 9 mm Hg at 8 hr, P less than 0.05). MAP was better maintained in the MP group (107 +/- 9 mm Hg vs. 80 +/- 16 mm Hg at 8 hr, P less than 0.05). Pulmonary function also was less affected in the MP group at 8 hr, with significantly better maintenance of arterial oxygenation (13.5 +/- 1.2 kPa vs. 9.4 +/- 2.2 kPa, P less than 0.05) less venous admixture (11 +/- 6% vs. 34 +/- 23%, P less than 0.05) and superior lung-thorax compliance (29 +/- 5 ml/cm H2O vs. 15 +/- 5 ml/cm H2O, P less than 0.05). Five of five with MP survived, whereas two of six without MP survived (P = 0.045). MP thus attenuated pulmonary and hemodynamic abnormalities induced by S. aureus septicemia.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1511507 TI - Increased plasma concentrations of hyaluronan after major thermal injury in the rat. AB - Hyaluronan (HYA) is an ubiquitous polysaccharide in connective tissue interstitium; its normal plasma concentration is in the nanogram/ml range. Following major burn injury in sheep, plasma HYA can increase to levels tenfold greater than normal. The present study aimed to determine the effects of major cutaneous burns on plasma HYA concentration in rat, since in this species, the HYA elimination kinetics may better resemble those in man. Thermal injury did not alter the weight-average molecular weight of HYA in skin. HYA concentration in plasma was 46 +/- 4 ng/ml (mean +/- SEM) in controls. Three hours after scald burns to 40% of the body surface area, plasma HYA was 61 +/- 10 ng/ml in unresuscitated animals (P less than 0.1 vs. controls). After fluid replacement by lactated Ringer's plasma HYA was 75 +/- 8 ng/ml (P less than 0.01 vs. control), whereas plasma infusion prevented the elevation of plasma HYA. HYA also increased significantly after lactated Ringer's infusion in noninjured animals. The increased plasma concentration of HYA after major burns is probably a consequence of increased lymph flow, increasing its transport from skin interstitium. Possibly, plasma concentrations of connective tissue components may be used as indicators of the severity and extent of burn injuries. PMID- 1511508 TI - Differential contractile responses of mesenteric and pulmonary artery segments to norepinephrine and phorbol ester in the septic pig. AB - The contractile response of isolated vascular segments was studied in Yucatan miniature swine approximately 48 hr after induction of sepsis by intraperitoneal injection of live Escherichia coli. Compared to non-septic controls, segments of the cranial mesenteric artery from septic animals showed a significantly attenuated contractile response to the adrenergic receptor agonist norepinephrine (NE). The EC50 for NE increased from 1.1 +/- 0.3 to 6.3 +/- 2.0 microM and the Emax decreased from 1,010 +/- 179 to 387 +/- 75 mg tension/mg tissue. In contrast, segments of the pulmonary artery showed no significant difference in contractility to NE between sham-operated and septic animals. Mesenteric and pulmonary artery segments from both septic and control animals exhibited similar contraction to the protein kinase C activator phorbol-12, 13-dibutyrate. This suggests that the observed hyporeactivity to NE in porcine mesenteric artery segments is not simply due to cellular damage by toxins associated with the septic state. The results also indicate that the impact of gram-negative sepsis on vascular contractile function varies between tissue from the systemic and pulmonary circulation in pigs. PMID- 1511509 TI - Urokinase in conditioned medium from phorbol ester-pretreated endothelial cells promotes polymorphonuclear leukocyte migration. AB - Serum-free conditioned medium (CM) generated by human umbilical vein endothelial cell monolayers following pretreatment with 100 ng/ml of phorbol myristate acetate (PMA) promoted human polymorphonuclear leukocyte (PMNL) migration as assayed in blindwell chambers. Stimulation of PMNL migration in response to CM was dependent on the dose of PMA used to pretreat the endothelial cells as well as the duration of incubation time to generate CM. Phorbol esters have been previously shown to release plasminogen activators from vascular endothelial cells. In the present study, pretreatment of endothelial cells with PMA also increased plasminogen activator activity in CM at a time course similar to the generation of PMNL chemoattractant activity. Treatment of CM with a polyclonal antibody against human urokinase-type plasminogen activator (uPA) not only inhibited uPA activity, but also significantly reduced PMNL chemoattractant activity when compared with untreated CM. In contrast, treatment of CM with an antibody directed against tissue-type plasminogen activator (tPA) did not affect PMNL migratory activity. Furthermore, when CM was passed over an anti-uPA immunoaffinity column, plasminogen activator activity was reduced 90% and chemoattractant activities was reduced 68%. Both plasminogen activator and chemoattractant activities were reconstituted in the eluate from the anti-uPA column. These data demonstrate that uPA present in the CM from PMA-pretreated endothelial cells stimulates PMNL chemoattractant activity and suggests a possible role for endothelial cell-derived uPA in stimulating migration of peripheral blood leukocytes at an inflammatory locus. PMID- 1511510 TI - Fundamentals of receptor theory: basics for shock research. AB - A variety of inflammatory mediators [e.g., tumor necrosis factor-alpha (TNF alpha)], endogenous hormones (e.g., epinephrine), and neurotransmitters (e.g., norepinephrine) are elevated as either a cause or a consequence of circulatory shock. The pathophysiologic responses observed during circulatory shock are the direct result of a complex interplay between the individual responses produced by the various mediators that interact with specific receptors. For example, as part of a compensatory response in circulatory shock, sympathetic outflow increases, which results in elevated synaptic levels of norepinephrine, which will activate alpha- and beta-adrenoceptors in the synaptic cleft. Additionally, plasma epinephrine and norepinephrine concentrations are elevated to a level sufficient to stimulate alpha- and beta-adrenoceptors in the heart, vasculature, and kidney, leading to profound changes in heart rate, cardiac output, peripheral vascular resistance, renal blood flow, and urine output. As such, the nature of the interaction between inflammatory mediators, hormones, and neurotransmitters with specific receptors in the cardiovascular system is fundamental to understanding the changes in circulatory status that occur during the shock state. PMID- 1511511 TI - 1,1,3 Tricyano-2-amino-1-propene (Triap) stimulates choline acetyltransferase activity in vitro and in vivo. AB - 1,1,3 Tricyano-2-amino-1-propene (Triap) is a small molecule that has neurotrophic properties similar to nerve growth factor (NGF). Studies have shown that NGF increases choline acetyltransferase (ChAT) activity, the enzyme responsible for the synthesis of acetylcholine, in several cell lines and in the CNS of adult animals. To investigate whether Triap can cause similar increases in ChAT enzyme activity, we used the PC12 cell line and primary cultures of rat fetal brain tissue to examine Triap's effects. Nanomolar concentrations of Triap produced a 4.2- and 2.1-fold increase in the ChAT activity of PC12 cells and cultured rat fetal brain cells, respectively. This stimulation reached a plateau within 4 days of treatment in the primary fetal brain cultures with the first increases evident within 24 h. In the PC12 cell line, Triap's stimulation of ChAT activity was significantly greater than increases produced by optimal concentrations of NGF. Triap also matched NGF's stimulation of ChAT activity in primary neuronal culture. Triap also potentiated NGF's actions on ChAT activity in the PC12 cell line and in primary fetal neuronal cultures. These increases in enzyme activity correlated with increases in cellular enzyme levels as assessed using immunochemical identification of the ChAT enzyme. We also conducted experiments to determine if Triap also induced these same increases in ChAT activity in adult animals. Ten-day chronic injections of Triap in mice resulted in significant increases in specific ChAT enzyme activity in the cortex and septal-hippocampal area. Similar increases in ChAT enzyme levels were also detected using western blotting techniques.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1511512 TI - Age dependency of the susceptibility of rats to aminooxyacetic acid seizures. AB - Immature rats are more susceptible to clonic seizures induced by aminooxyacetic acid (AOAA) than mature and senile rats. Highest susceptibility to AOAA seizures was observed in 7-14-day-old rat pups. The lowest susceptibility was recorded in 10-20 month-old rats. AOAA seizures in 14-day-old rats were blocked by clonazepam and valproate, but not by phenobarbital, carbamazepine, diphenylhydantoin, trimethadione or ethosuximide. Morphological analysis of brains from 14-day- and 3-month-old rats which experienced AOAA seizures did not reveal epilepsy-related damage. These observations suggest that immature rat brain is highly prone to convulsions induced by AOAA and that such convulsions are difficult to control by available antiepileptic treatment. PMID- 1511513 TI - Neuronal cell loss in heterozygous staggerer mutant mice: a model for genetic contributions to the aging process. AB - Staggerer is a neurological mutation of mice that causes a severe ataxia correlated with digenesis of the cerebellar cortex. The Purkinje cell population in the homozygous mutant is reduced in size with a near total atrophy of dendritic structure. Further, the cells are ectopic and are reduced in number by about 75%. All of these phenotypes have been shown to be direct effects of the staggerer gene on the Purkinje cell itself. As an indirect consequence of gene action, virtually all of the cerebellar granule cells die as do 60% of the cells of the inferior olive. The mutation is described as recessive because of the heterozygote, +/sg, is behaviorally normal and the mature cerebellum shows none of the defects described in the homozygous mutant. We report here that, as the +/sg mouse advances in age, a syndrome of cell losses is observed. While these losses are not as severe as in the homozygote, by 12 months of age 35% of the Purkinje cells are gone, as are 35% of the granule cells and 40% of the cells in the inferior olive. We propose that these results illustrate a synergy between the aging process and the heterozygous genotype. Neither alone is sufficient to cause the cell loss. This interaction suggests that the +/sg represents a new model for the genetic contribution to regressive CNS changes during aging. PMID- 1511514 TI - Development of AChE-positive neuronal projections from basal forebrain to cerebral cortex in organotypic tissue slice cultures. AB - Development of the innervation of the cerebral cortex by acetylcholinesterase (AChE)-stained basal forebrain neurons was studied in vitro using the roller tube technique. Slice cultures were maintained from 3 days to 4 weeks either in serum based medium or in chemically defined medium, each supplemented in some cases with nerve growth factor (NGF). The distribution of AChE and choline acetyltransferase (CAT)-containing neurons was investigated using histo- and immunocytochemical techniques. Slice cultures of basal forebrain revealed the presence of large and medium sized AChE-positive neurons. Within one week of cultivation, numerous AChE-labeled fibers could be seen growing out from the basal forebrain toward the cortex. After entering cortical tissue most of the afferent basal forebrain fibers projected either radially or obliquely into the cortical layers. Many afferent axons initially also travelled tangentially within the white matter, and turned then to grow into the cortical layers. Cerebral cortex tissue maintained a coarse laminar organization. Ramifications of basal forebrain fibers were visible within the subplate region, the deep and superficial cortical layers, and within the marginal zone; greatest density occurred in the subplate region and in marginal zones. Many of these processes exhibited branching patterns markedly similar to those observed during cortical development in vivo. Cortex slices placed with the pial surface adjacent to the basal forebrain revealed AChE-stained fibers that entered the cortical tissue through the marginal surface and gave off ramifications within the superficial layers and, less frequently, the deeper cortical layers. CAT-immunostaining revealed labeled cell bodies and neurites only in the basal forebrain, not in the cortex tissue. Control experiments with co-cultures of basal forebrain and cerebellum slices showed no AChE-positive fiber ingrowth into the cerebellum tissue. The results of these studies demonstrate that basal forebrain projections to cerebral cortex in vitro appear similar to the projections that develop in vivo, and indicate that organotypic co-cultures provide a valuable model for studies of developing cortical afferents. PMID- 1511515 TI - Actin-binding proteins in the growth cone particles (GCP) from fetal rat brain: a 44 kDa actin-binding protein is enriched in the fetal GCP fraction. AB - Neuronal growth cones, the motile tips of growing neurites, are thought to play a significant role in nerve growth. To study the role of actin in their motility, we examined actin-binding proteins in growth cone particles (GCP) isolated from fetal rat brain, using a blot-overlay method with biotinylated actin. Among the more than ten species of actin-binding proteins in the GCP, a 44 kDa protein was found specifically in growth cones and was enriched in the cytoskeletal and the membrane skeletal subfractions from the GCP. This protein binds to actin in a Ca(2+)- and Mg(2+)-dependent manner, and ATP enhances its binding to actin. The protein was predominantly present in the fetal GCP, but it is expressed at a much lower level in the neonatal GCP and not detected in adult synaptosomes. The protein also bound to a deoxyribonuclease I column and was eluted by EGTA containing buffer. The 44 kDa protein appears to be a novel actin-binding protein, since none of the known actin-binding proteins exhibit this combination of properties. Our results suggest that the protein may be involved with the early stages of neurite extension. PMID- 1511516 TI - Sexual dimorphism of the dopamine-beta-hydroxylase-immunoreactive neurons in the rat locus ceruleus. AB - Sex differences in the noradrenaline synthesizing neurons of the locus ceruleus (LC) in rat brain were investigated immunocytochemically using an antibody to dopamine-beta-hydroxylase. Female adult rats contained a greater structural volume and average somatic area in the anterior intermediate region of the nucleus compared with males. Whether this difference is related to the endocrine status of the animals, and consequently a functionally distinct population of neurons, is yet to be determined. PMID- 1511517 TI - Pre- and postnatal development of noradrenergic projections to the rat spinal cord: an immunocytochemical study. AB - Using immunocytochemistry with a specific antiserum against noradrenaline, the pre- and postnatal development of noradrenergic (NA) projections to the rat spinal cord was studied from embryonic day 16 (E16) to adulthood (the day following nocturnal mating being considered as E0). In this study, pregnant animals were pre-treated with the MAO inhibitor pargyline (200 mg/kg i.p.), whereas postnatal animals received 100 mg/kg. In vibratome sections, noradrenaline-immunoreactive (NA-IR) axons were seen to invade the spinal cord at E16, at cervical and upper thoracic levels, from the ventral funiculus. At E18, small caliber NA-IR fibers were present in the ventral horn at all cord levels, and some fibers were seen in the intermediolateral cell column (IML) at thoracic level. The growth of axons towards the dorsal horn became noticeable by postnatal day 0 (P0). At P3, fine beaded and radially orientated NA-IR fibers were observed at all levels. The pattern of NA innervation of the dorsal horn was similar to that of the adult by P7. The segregation of noradrenaline immunoreactivity in the ventral and dorsal horns, the IML and the periependymal area was more obvious at all levels by P14 and P20. From P30 the NA innervation was similar to that found in the adult spinal cord. Thus, noradrenaline, like serotonin, was present early in the spinal cord before the onset of specific functions. In addition to and prior to its transmitter function, it might play a trophic role in the neurogenesis of the spinal cord. PMID- 1511518 TI - On the ontogenetic and sequential characteristics of bombesin-induced grooming in the infant rat. AB - This paper examined the grooming effects of central injections of the tetradecapeptide bombesin (BN) in the infant rat. Anaesthetized rat pups of 1-20 days of age (n = 7/dose/age) were injected intracerebroventricularly (i.c.v.) with either BN (0.01-1.0 micrograms) or saline (control condition) and placed in heated test cages. Following recovery from the anaesthetic, the subsequent behaviour displayed by the pups was videotaped for the next 60 min. These videotaped responses were then scored for a variety of grooming and other behaviours. Pups of all ages (1-20 days) groomed in response to BN with the 1-day old pups the least and 20-day-olds the most sensitive to BN. In the 10-day-olds, scratching, in an immature, non-contact form, was elicited by BN. This was replaced by mature, contact type scratching in the sequence of grooming behaviour at 20 days of age. Scratching activities appeared to form a subsystem connected to but nonetheless separate from washing behaviours and this was particularly distinguishable at 20 days of age. Changes in BN-induced grooming appeared to reflect the maturation of the motor capabilities of the developing rat. In conclusion, these results indicate that BN binding sites in the developing rat central nervous system (CNS) are pharmacologically functional from an early stage in ontogeny when there is little or no measurable amount of the peptide itself present in the CNS. PMID- 1511519 TI - Carbonic anhydrase in distinct precursors of astrocytes and oligodendrocytes in the forebrains of neonatal and young rats. AB - Carbonic anhydrase is present in oligodendrocytes and astrocytes in the mature rat brain. Whereas carbonic anhydrase-positive oligodendrocyte precursors had been identified during the first postnatal week, no information was available about the earliest occurrence of carbonic anhydrase in the astrocytic cell line, nor had carbonic anhydrase been detected in astrocytes in neonatal rat brains. Beginning on the first postnatal day, rat brains were double immunostained with anti-carbonic anhydrase II and respective 'markers' for immature and mature astrocytes and oligodendrocytes. During the first postnatal week there were intensely carbonic anhydrase-positive cells which were ovoid or had broad processes. On the basis of their shapes and antigen contents these were considered to be precursors of oligodendrocytes. Beginning on the first postnatal day carbonic anhydrase II was also observed in some vimentin-positive radial glia and in other vimentin-positive cells that differed in their appearance from the immature oligodendrocytes. The vimentin-positive, carbonic anhydrase-positive cells were less smooth-surfaced, and had much finer processes, than the oligodendrocyte precursors. By the third postnatal day there appeared carbonic anhydrase-positive, glial fibrillary acidic protein (GFAP)-positive cells that resembled the vimentin-positive cells. It is concluded that the latter are immature astrocytes and that carbonic anhydrase is in distinct precursors of oligodendrocytes and astrocytes as early as the first postnatal day. PMID- 1511520 TI - A developmentally regulated plasmalemmal antigen present in synaptosomes but not in growth cones. AB - Monoclonal antibody 2L4 was generated against rat synaptosomes but does not cross react with nerve growth cones. Expression of the 2L4 antigen is developmentally regulated in a manner that is, in part, the opposite of the expression of the 5B4 CAM antigen, a marker of neuronal outgrowth belonging to the N-CAM family. While 5B4-CAM appears and increases during sprouting and then decreases to reach low levels in the adult, the 2L4 antigen appears only late in development, when neuronal outgrowth ceases, at or around the time of synaptogenesis. Once expressed, the antigen is found on the entire plasmalemmal surface of the neuron, but seems to be enriched at synaptic endings, at least of some neuron types. Biochemical analyses involving blotting of non-denaturing gels and immunoaffinity chromatography identify the antigen as a pair of polypeptides with similar, basic isoelectric points. These polypeptides form a somewhat diffuse, probably glycosylated band at 67 kDa and may be part of a hetero-oligomeric complex. The localization, biochemical, and developmental results suggest that the 2L4 antigen is a plasmalemmal marker of maturing and/or mature neurons whose expression may be triggered by synaptogenesis. PMID- 1511521 TI - The organization of radial glial fibers in spontaneous neocortical ectopias of newborn New Zealand black mice. AB - Forty percent of New Zealand Black (NZB) mice, a strain that develops severe autoimmune disease, have ectopic collections of neurons in layer I of the neocortex. This strain is used as a model for similar anomalies seen in the dyslexic brain. In the present study we immunohistochemically stained radical glial fibers and their anchoring processes (which form the glial external limiting membrane) in the region of ectopias in NZB mice. The organization of glial fibers was abnormal in and around the ectopic region. Radial glial fibers underlying the ectopia were denser than in the surrounding cortex, and within the ectopia there was a disorganized matrix of glial fibers. Most glial fibers, however, did not enter the ectopia, but instead curved towards the edge of the ectopia and attached there. The glial limiting membrane was breached in the area of the ectopia, indicating that an insult to this membrane may have allowed neurons to migrate into layer I and the overlying subarachnoid space. This finding along with the results of the accompanying paper on puncture wounds of the cortex of newborn rodents supports the view that rupture of the external limiting glial membrane is responsible for the inappropriate migration of neurons into the molecular layer. PMID- 1511522 TI - Development of tone response thresholds, latencies and tuning in the mouse inferior colliculus. AB - The development of tone response thresholds, latencies and tuning of neurons in the inferior colliculus (IC) of the mouse has been investigated between postnatal days 10 (first responses) and 20. As in adults, response thresholds of neurons are lowest in the center of the IC compared with other areas right from the beginning of responsiveness at day 10. Thresholds decrease rapidly until at days 16-20 (depending on the characteristic frequency of the neurons) adult levels are reached. Response latencies decrease rapidly to adult levels at days 16-18. Broad frequency tuning curves can be measured at days 10 and 11. From day 12 onwards, tuning curve shapes differentiate and adult diversity occurs which indicates presence of inhibition and summation in the pathway to or within the IC at that early age. The tip lengths of the tuning curves increase faster than the sharpness of the tips (Q10 dB values). The developmental courses of the measured parameters are expressed by power functions. The time constants of these functions are used in the discussion of processes underlying the functional maturation in the auditory system of the mouse. The general course of the development of all the here investigated response properties of single neurons in the IC, except tuning curve shape, appears to be determined by maturation at or peripheral to the cochlear level. PMID- 1511523 TI - Dendritic morphology of interstitial amacrine cells with monostratified dendrites in different-sized carp retinas. AB - The dendritic morphology of a class of interstitial (IS) amacrine cells in retinas of different-sized carp (body length, 9.1-32.3 cm) was investigated by identifying their fluorescent nuclei pre-loaded with 4,6-diamidino-2-phenylindole (DAPI), followed by iontophoretic injection of Lucifer yellow (LY) in isolated and formaldehyde-fixed flat-mounts under microscopic control. The LY-injected fusiform or pyriform cell bodies were found to locate at the middle of the inner plexiform layer (IPL) or immediately beneath the amacrine cell layer, and their dendrites monostratified in sublamina b of the IPL. The pyriform cells had a short stem from which extended 4-5 stout dendrites, while the fusiform cells extended similar dendrites from the soma. The dendrites of both types of cell were decorated with spines and a few long axon-like processes. The pyriform cells were found more frequently in smaller retinas than in larger retinas, suggesting that the former may migrate proximally during retinal growth. The dendritic field sizes of these IS amacrine cells were wider as the fish became larger, while the dendritic morphology, analyzed by the Sholl's branching model, was very similar in smaller and larger retinas. The results indicate that the IS amacrine cells do not add dendrites, but that their dendritic trees simply expand during retinal growth. PMID- 1511524 TI - Delayed changes of chromogranin A immunoreactivity (CgA ir) in human striate cortex during postnatal development. AB - The changes in chromogranin A expression in the human striate cortex from birth till 67 years were studied by immunohistochemical method in 18 autopsied patients. The first chromogranin A immunoreactivity (CgA ir) was identified at birth in layer IV (especially IVc) mainly as fine nerve terminals. By 6 months, the first perikaryal reactivity was noted in the large pyramidal neurons of layer V. The smaller neurons in layers IV, V and VI showed a progressive increase in CgA ir from 15 months to about 17 years. At approximately 9 years, immunoreactivity began to be noted in supragranular neurons in layers II and III. The final laminar distribution of CgA ir seemed to be attained at about 25 years with relatively little change thereafter. The CgA ir in the striate cortex demonstrates a prolonged period of developmental changes, lasting from birth to about 25 years. PMID- 1511525 TI - The development of neuropeptide Y immunoreactive neurons in cat visual cortical areas. AB - The development of NPY-ir neurons and fibers in cat striate and extrastriate cortex was studied to determine whether temporal changes in the morphology, distribution and density of NPY-ir neurons during development would provide clues to the emergence of specific cortical areas. No differences in the number or distribution of NPY-ir neurons were observed at any age among the five visual cortical areas examined, area 17, 18, 19, posteromedial lateral suprasylvian and posterolateral lateral suprasylvian cortex. The number of NPY-ir neurons in cat visual cortical areas was higher in adult animals than in kittens. The proportion of NPY-ir neurons found in layer VIb was constant throughout life, suggesting that NPY immunoreactivity is not a marker for the transient neurons of the subplate. NPY-ir neuronal morphology was seen to 'flatten' in older animals with the development of sulci and increasing density of the brain. In contrast to the pattern observed with NPY-ir neurons, NPY-ir processes exhibited area-dependent differences during development. NPY-ir fibers grew into area 17 earlier and with a radial orientation which was not consistently observed laterally. This radial orientation was still apparent in adult brains in layer IV of area 17, though there was no orientation of fibers in the other laminae or other visual areas of the adult. PMID- 1511526 TI - Age-related anticonvulsant activity of NMDA in the rat caudate-putamen. AB - Striatal pathways are important for modulating the threshold for seizures in the rat forebrain. N-Methyl-D-aspartate (NMDA), an excitatory amino acid derivative and powerful anticonvulsant agent, when injected into the brain, has been shown to protect adult rats against kindling and pilocarpine-induced seizures when injected into the caudate-putamen. The present study examines whether the anticonvulsant action of NMDA in the caudate-putamen varies with age. Bilateral striatal administration of NMDA was effective in suppressing bicuculline-induced seizures in rats older than 23 days of age. The results suggest that striatal pathways involved in the anticonvulsant activity of NMDA in the caudate-putamen are not functionally active in developing rats before the 4th week of life. PMID- 1511527 TI - Use of [3H]-GBR12935 to measure dopaminergic nerve terminal growth into the developing rat striatum. AB - In this study we determined the temporal association between the appearance of the dopamine transporter, measured by 1-[2-(diphenyl-methoxy)ethyl]-4-(3- phenylpropyl)-piperazine ([3H]-GBR12935), a potent and selective inhibitor of dopamine uptake, and other biochemical markers of dopaminergic nerve terminal growth into the developing striatum. [3H]-GBR12935 binding was minimally detected in the rudimentary striatum of embryonic day 14 rat brains, increased to 23% of the adult level by birth, and reached the adult level during the fifth postnatal week. This finding contrasts with a slower developmental increase in [3H] dopamine uptake, a functional measure of the transporter. Tyrosine hydroxylase activity levels followed a developmental curve similar to that of [3H]-GBR12935 binding but did not reach adult levels until the 7th postnatal week. Dopamine content increased at a slower rate, being only 10% and 92% of the adult level at birth and postnatal week 8, respectively. These results indicate that the appearance of a structural, but not optimally functional, dopamine transporter may be the earliest detectable biochemical index of dopaminergic nerve terminal growth into the striatum during development. PMID- 1511528 TI - Pharmacokinetic drug interactions of macrolides. AB - The macrolide antibiotics include natural members, prodrugs and semisynthetic derivatives. These drugs are indicated in a variety of infections and are often combined with other drug therapies, thus creating the potential for pharmacokinetic interactions. Macrolides can both inhibit drug metabolism in the liver by complex formation and inactivation of microsomal drug oxidising enzymes and also interfere with microorganisms of the enteric flora through their antibiotic effects. Over the past 20 years, a number of reports have incriminated macrolides as a potential source of clinically severe drug interactions. However, differences have been found between the various macrolides in this regard and not all macrolides are responsible for drug interactions. With the recent advent of many semisynthetic macrolide antibiotics it is now evident that they may be classified into 3 different groups in causing drug interactions. The first group (e.g. troleandomycin, erythromycins) are those prone to forming nitrosoalkanes and the consequent formation of inactive cytochrome P450-metabolite complexes. The second group (e.g. josamycin, flurithromycin, roxithromycin, clarithromycin, miocamycin and midecamycin) form complexes to a lesser extent and rarely produce drug interactions. The last group (e.g. spiramycin, rokitamycin, dirithromycin and azithromycin) do not inactivate cytochrome P450 and are unable to modify the pharmacokinetics of other compounds. It appears that 2 structural factors are important for a macrolide antibiotic to lead to the induction of cytochrome P450 and the formation in vivo or in vitro of an inhibitory cytochrome P450-iron nitrosoalkane metabolite complex: the presence in the macrolide molecules of a non-hindered readily accessible N-dimethylamino group and the hydrophobic character of the drug. Troleandomycin ranks first as a potent inhibitor of microsomal liver enzymes, causing a significant decrease of the metabolism of methylprednisolone, theophylline, carbamazepine, phenazone (antipyrine) and triazolam. Troleandomycin can cause ergotism in patients receiving ergot alkaloids and cholestatic jaundice in those taking oral contraceptives. Erythromycin and its different prodrugs appear to be less potent inhibitors of drug metabolism. Case reports and controlled studies have, however, shown that erythromycins may interact with theophylline, carbamazepine, methylprednisolone, warfarin, cyclosporin, triazolam, midazolam, alfentanil, disopyramide and bromocriptine, decreasing drug clearance. The bioavailability of digoxin appears also to be increased by erythromycin in patients excreting high amounts of reduced digoxin metabolites, probably due to destruction of enteric flora responsible for the formation of these compounds. These incriminated macrolide antibiotics should not be administered concomitantly with other drugs known to be affected metabolically by them, or at the very least, combined administration should be carried out only with careful patient monitoring.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1511529 TI - P450 enzymes. Inhibition mechanisms, genetic regulation and effects of liver disease. AB - Multiple hepatic P450 enzymes play an important role in the oxidative biotransformation of a vast number of structurally diverse drugs. As such, these enzymes are a major determinant of the pharmacokinetic behaviour of most therapeutic agents. There are several factors that influence P450 activity, either directly or at the level of enzyme regulation. Drug elimination is decreased and the incidence of drug interactions is increased when there is competition between 2 or more drugs for oxidation by the same P450 enzyme. The available knowledge concerning the relationship between the presence of certain functional groups within the drug structure and inhibition of P450 activity is increasing. In many instances, it is possible to associate inhibition with certain drug classes, e.g. antimycotic imidazoles and macrolide antibiotics. Disease states, especially those with hepatic involvement, and the genetic makeup of the individual are conditions in which some P450s may be downregulated (that is, the enzyme concentrations in liver are decreased), with associated slower rates of drug elimination. In these individuals, dosages of drugs that are substrates for downregulated P450s should be decreased. Exposure to environmental pollutants as well as a large number of lipophilic drugs can result in induction (upregulation) of P450 enzyme activity. This raises the issue of previous approaches to the study of P450 induction in vivo. The use of human hepatocyte preparations in culture is a promising new direction that could assist the determination of modifications to drug therapy necessitated by exposure to inducing agents. Until such information is obtained, however, the use of drugs known to increase the microsomal expression of particular P450s, and increase associated drug oxidation capacity in humans, should be used with caution. PMID- 1511530 TI - Clinical pharmacokinetics of alpha 1-antitrypsin in homozygous PiZ deficient patients. AB - A pharmacokinetic study of alpha 1-antitrypsin (ATT) was performed in 2 groups of homozygous PiZ-deficient patients (treated and untreated) and 1 group of healthy volunteers. The distribution of the 131I-labelled protein corresponds to a 3 compartment model. The intravenously administered protein diffused quickly to the extravascular compartment where some retention occurred. No significant difference in AAT metabolism was observed between the 3 groups. The half-life of the injected protein is slightly longer than 2.5 days. The AAT protein was not stored. These results confirm the observations collected during the clinical trials. That is, a weekly infusion is necessary to obtain stable serum AAT concentrations. Monthly infusions are unable to maintain a 'plateau' phase. The periodicity may be limited to every 2 weeks. PMID- 1511531 TI - Monoclonal antibody administration. Current clinical pharmacokinetic status and future trends. PMID- 1511532 TI - The use of low dose aspirin in pregnancy. PMID- 1511533 TI - Pharmacokinetics of drugs in overdose. AB - The pharmacokinetics of drugs may be altered following an overdose. The degree of absorption depends on the physical characteristics of the drug; the rate of dissolution may delay or broaden peak serum concentrations. The pathophysiological effects of a drug may also limit or augment absorption. Altered distribution of drugs in overdose results from changes in the extent of protein binding and size of the volume of distribution. Saturation of hepatic enzyme systems in overdose is manifested by delayed metabolism or elimination of many drugs; renal elimination of unchanged drug may take on greater importance in this instance. Familiarity with the toxicokinetic profile of a given drug enables the physician to exploit these principles in order to limit toxicity. Delayed or prolonged absorption allows for late decontamination. Multiple doses of activated charcoal are effective in interrupting both entero-enteric and enterohepatic recirculation. Alkalinisation-induced ion trapping enhances renal elimination of unchanged drugs which normally undergo hepatic transformation. For several drugs, chronic overdose due to altered distribution is associated with a greater severity of toxic manifestations despite relatively low serum drug concentrations. Conversely, with some drugs, induction of metabolic pathways may lead to more rapid drug elimination in chronic overdose. Knowledge of the pharmacokinetic alterations which occur in drug overdose enables the physician to predict toxicity with greater accuracy and to institute optimum therapy in a timely manner. PMID- 1511534 TI - Nicotine therapy in smoking cessation. Pharmacokinetic considerations. PMID- 1511535 TI - A review of assay methods for cyclosporin. Clinical implications. AB - Cyclosporin is a unique immunosuppressive agent with a narrow therapeutic range. The pharmacokinetics of the drug present substantial within- and between-patient variability and drug interactions can significantly alter blood cyclosporin concentrations. Monitoring of cyclosporin concentrations in blood is an invaluable and essential aid in adjusting dosage to ensure adequate immunosuppression while minimising toxicity. The principal rationale behind therapeutic monitoring of cyclosporin is the fact that the incidence of rejection is higher at low cyclosporin concentrations and toxicity occurs more often at high concentrations. In renal transplant recipients, cyclosporin concentrations help to discriminate between insufficient immunosuppression and cyclosporin induced nephrotoxicity. There are several methods available, both specific and nonspecific, for the routine measurement of cyclosporin. Radioimmunoassay and fluorescence polarisation immunoassay are most widely employed, while high performance liquid chromatography remains the reference procedure. The allegedly specific immunoassays tend to slightly overestimate the actual blood cyclosporin concentrations. There is a need for assay systems capable of measuring the biological activity of cyclosporin. Cyclosporin concentrations should be determined by a specific method, using whole blood as the sample matrix. The routine monitoring of individual cyclosporin metabolites is not warranted, but characterising the metabolite pattern of cyclosporin by concomitant use of a nonspecific and a specific assay can be clinically useful in patients with cyclosporin-associated toxicity or impaired liver function. In organ transplantation, measurement of blood cyclosporin concentration should be continued periodically as long as the therapy continues, whereas monitoring is only indicated in special circumstances in patients with autoimmune and other nontransplant diseases. The assessment of a 'therapeutic window' for cyclosporin is complicated for several reasons and definite target ranges cannot be given. Cyclosporin concentrations should always be interpreted in conjunction with the recent blood concentration history and other relevant clinical and laboratory data. PMID- 1511538 TI - FDA approves release of recombinant interleukin-2 product. PMID- 1511539 TI - Use of ursodiol in a patient with biliary cirrhosis. PMID- 1511536 TI - Electroencephalogram effect measures and relationships between pharmacokinetics and pharmacodynamics of centrally acting drugs. AB - Electroencephalogram (EEG) effect parameters may be useful in pharmacokinetic pharmacodynamic modelling studies of drug effects on the central nervous system (CNS). Effect parameters derived from a quantitative analysis of the EEG appear to be perfectly suited to characterise the relationships between pharmacokinetics and pharmacodynamics of benzodiazepines and intravenous anaesthetics. EEG parameters represent many of the characteristics of ideal pharmacodynamic measures, being continuous, objective, sensitive and reproducible. These features provide the opportunity to derive concentration-effect relationships for these drugs in individuals, which yield important quantitative information on the potency and intrinsic efficacy of these drugs. The EEG techniques presented can be used to study the influences of factors such as age, disease, chronic drug use and drug interactions on the concentration-effect relationships of psychotropic drugs. An important issue is the choice of the EEG parameter to characterise the CNS effects of the compounds. More attention must be paid to evaluating the relevance of EEG parameters to the pharmacological effects of the drugs. Knowledge of the relationship between EEG effect parameters and clinical effects of drugs under different physiological and pathophysiological conditions is crucial to determining the value of EEG parameters in drug effect monitoring. Pharmacodynamic parameters derived from the concentration-EEG effect relationship may be correlated to pharmacodynamic parameters obtained from other in vitro and in vivo effect measurements. These comparisons revealed that changes in the amplitudes in the beta frequency band of EEG signals is a relevant measure of pharmacological effect intensity of benzodiazepines, which reflects their affinity and intrinsic efficacy at the central gamma-aminobutyric acid (GABA) benzodiazepine receptor complex. The exact EEG correlates of the anxiolytic, anticonvulsant, sedative and hypnotic actions of benzodiazepines have not yet clearly been elucidated. For intravenous anaesthetics, close correlations between the potency determined with EEG measurements and clinical measures of anaesthetic depth have been established, suggesting that, in principle, EEG parameters can adequately reflect depth of anaesthesia. However, more study is required to further substantiate these findings. PMID- 1511537 TI - Pharmacokinetic optimisation of anticonvulsant therapy. AB - Changing attitudes towards the use of antiepileptic drugs have led to an emphasis on monotherapy with serum concentration measurement coupled with standard, weight adjusted starting and maintenance regimens to guide initial therapy and subsequent dosage titration. Currently, the established anticonvulsants are carbamazepine, valproic acid (sodium valproate) and phenytoin. Phenobarbital is now less commonly prescribed due to its propensity to produce sedation and impair cognitive function. The value of pharmacokinetic optimisation with valproic acid is limited by its wide therapeutic index, large fluctuations in the concentration time profile and concentration-dependent protein binding. Thus, although serum concentrations are often measured, they are rarely subjected to pharmacokinetic interpretation. Carbamazepine has a flatter concentration-time profile than valproic acid. Its target range is more clearly defined and it undergoes autoinduction of metabolism and interacts with other drugs. Pharmacokinetic principles can, therefore, be more readily applied to carbamazepine, although, in general, a simple clinical approach to its use is usually satisfactory. Phenytoin has required the greatest pharmacokinetic input due to its nonlinear pharmacokinetics and narrow target range. Many different graphical methods, equations and computer programs have been reported, some of which demand 2 steady state, dose-concentration pairs; others function satisfactorily with only 1. Recent attempts have been made to interpret non-steady-state data. In addition, a number of workers have demonstrated the value of altering the population parameter estimates to account for ethnic differences. A pharmacokinetic approach can also be used to tailor the use of phenytoin in the treatment of status epilepticus. Dosage alterations may be needed for specific patient groups. In particular, children generally require higher dosages on a weight-for-weight basis than adults, while equivalently lower dosages should be given to neonates. Most anticonvulsants are principally cleared by hepatic mechanisms, so dosage adjustment is not usually required in renal disease, although care must be taken in interpreting serum concentrations because of changes in protein binding. Close monitoring is required in the elderly and patients with hepatic impairment, while increased dosages may be needed in critically ill patients and during pregnancy. Pharmacokinetic principles can be used in the treatment of treat self-poisoning with anticonvulsants. There are few data available on the pharmacokinetics of vigabatrin, lamotrigine, oxcarbazepine and gabapentin in patients. Due to its mode of action in binding irreversibly to its target enzyme, serum concentration monitoring of vigabatrin plays no role in optimising therapy. The value of applying pharmacokinetic principles with the other 3 drugs remains to be investigated.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1511540 TI - Potential interaction between terfenadine and macrolide antibiotics. PMID- 1511541 TI - Pravastatin: a new drug for the treatment of hypercholesterolemia. AB - The chemistry, pharmacology, pharmacokinetics, clinical trials, adverse effects, role in lipid-lowering therapy, and dosage and administration of pravastatin are reviewed. Pravastatin sodium is a new 3-hydroxy-3-methylglutaryl-coenzyme A (HMG CoA) reductase inhibitor for the treatment of hypercholesterolemia. Its structural formula is similar to those of lovastatin and simvastatin, but it is active in the parent form. It competitively inhibits HMG-CoA reductase, reduces hepatic cellular cholesterol synthesis, increases the expression of hepatic low density lipoprotein (LDL) receptors, and reduces hepatic very low-density lipoprotein (VLDL) synthesis. Pravastatin has been demonstrated to reduce cholesterol in patients with familial and nonfamilial polygenic hypercholesterolemia and patients with diabetes mellitus. In doses of 10-40 mg/day, pravastatin has been shown to reduce total cholesterol by 15-30% and LDL cholesterol by 15-40%. It also increases high-density lipoprotein cholesterol by 2-20% and reduces triglycerides. It is generally well tolerated, with few adverse effects reported in clinical trials. Pravastatin reduces LDL cholesterol and increases HDL cholesterol comparably to lovastatin but possibly with fewer adverse effects. Further studies and clinical use will be needed to confirm potential differences in adverse effect profiles between the two drugs. PMID- 1511542 TI - Treatment of nonsteroidal anti-inflammatory drug-induced gastropathy. AB - The etiology, natural history, epidemiology, prevention, and treatment of nonsteroidal anti-inflammatory drug (NSAID)-induced gastrointestinal (GI) effects are reviewed. Current evidence suggests that NSAIDs cause acute cellular damage by a topical effect that is exacerbated by impaired healing. Although acute gastric injury from NSAIDs is rapid and almost uniform from patient to patient, not all patients develop serious chronic injury. Some adaptation to the effects of NSAIDs does occur. Endoscopic studies have found that 14-31% of long-term NSAID users have gastric or duodenal ulcers. Data on individual drugs are inconsistent, but they suggest that enteric-coated aspirin, salsalate, and ibuprofen cause the lowest incidence of GI hemorrhage. Preventive measures tested to date include reduction in gastric acid production (histamine H2-receptor antagonists) and attempts to increase mucosal defenses (sucralfate or misoprostol). Misoprostol is the only drug with FDA-approved labeling for prevention of NSAID-induced gastropathy. NSAID-related ulcers heal in most patients within two to three months when they are treated with H2-receptor antagonists with or without antacid, omeprazole, or misoprostol. In patients with multiple risk factors, prophylaxis with misoprostol would be appropriate unless the clinician is concerned solely about reactivation of a duodenal ulcer, in which case an H2-receptor antagonist would also be appropriate. Full-dose treatment with H2-receptor antagonists, omeprazole, or misoprostol will heal NSAID-induced ulcers, even when NSAID therapy is continued. PMID- 1511543 TI - Endocrine complications associated with human immunodeficiency virus infection. AB - The causes and management of endocrine disorders associated with human immunodeficiency virus (HIV) infection are reviewed. Endocrine disorders observed in HIV-positive patients include adrenal abnormalities, hyporeninemic hypoaldosteronism, pituitary insufficiency, pancreatic abnormalities, thyroid and parathyroid disorders, and testicular abnormalities. Opportunistic pathogens implicated in these disorders include cytomegalovirus, Cryptococcus, Toxoplasma, mycobacteria, Candida, and Aspergillus. Neoplasma such as Kaposi's sarcoma and lymphoma can also cause endocrine abnormalities. Several drugs used in patients with the acquired immunodeficiency syndrome (AIDS) are associated with the development of endocrine disorders. These drugs include ketoconazole, itraconazole, rifampin, vidarabine, pentamidine, trimethoprim-sulfamethoxazole, didanosine, and ganciclovir. Severe patient debilitation can contribute to the development of endocrine abnormalities. Monitoring of adrenal gland function may be prudent in HIV-infected patients who have nonspecific symptoms of adrenal insufficiency. If adrenal insufficiency is diagnosed, replacement therapy with oral hydrocortisone is required. Administration of fludrocortisone can rapidly alleviate the signs and symptoms of hyporeninemic hypoaldosteronism. Fluid restriction is the first step in managing the pituitary abnormality known as the syndrome of inappropriate secretion of antidiuretic hormone. Drug-induced endocrine abnormalities often resolve after withdrawal of the offending agent. Endocrine complications in HIV-infected patients may be caused by infection, malignancy, or drugs. Adjusting or instituting drug therapy may be necessary to control symptomatic endocrine abnormalities. PMID- 1511544 TI - Are antiarrhythmic drugs obsolete? PMID- 1511545 TI - Criteria for use of adenosine in adults with paroxysmal supraventricular tachycardia. PMID- 1511546 TI - Occupational lung diseases. PMID- 1511547 TI - Air measurements of dusts, chemicals, and fumes. AB - Estimates of exposure in the workplace or in indoor environments begin with the actual sampling and analysis of the airborne contaminant or rely on a reconstruction of past exposures in the workplace. Direct-reading portable field instruments are being used to supplement laboratory-based analytical methods. The lowering of the OSHA permissible exposure limits and the rise of indoor air pollution concerns indicate the need for more innovative methods for detecting lung irritants and pathogens. PMID- 1511548 TI - Engineering controls for clean air in the office environment. AB - Supply of adequate amounts of fresh air, properly conditioned, is crucial to maintaining good air quality in the office environment. Building managers frequently attempt to limit the amount of fresh air supplied to offices, because of the energy costs involved. It is important that the amount of fresh air being supplied be evaluated by competent personnel and that substandard conditions be rectified. It is also important that ventilation systems be properly maintained. If these fairly simple steps are taken, many complaints of poor air quality will be eliminated. PMID- 1511549 TI - Health effects of air pollution. A review of clinical studies. AB - The database for the acute health effects of common outdoor air pollutants is rapidly increasing but important gaps still exist. Greater technical efforts and innovative studies are required to adequately characterize health effects and understand the underlying mechanisms of toxicity. Controlled human exposures provide relevant data about short-term effects and complement animal and epidemiologic investigations. Except for possibly nitrogen dioxide, the clinical data for ozone, sulfur dioxide, and particulates (H2SO4) at contemporary levels indicate potentially untoward or adverse physiologic or clinical responses in healthy individuals and sensitive groups such as children, adolescents, and asthmatic patients. Exercise, duration, and other exposure factors may potentiate pollutant effects on symptoms, lung function, nonspecific bronchial reactivity, mucociliary clearance, and BAL markers of inflammation. Continued animal, clinical, and epidemiologic research of both short- and long-term health effects is clearly needed to support or limit future regulatory decisions regarding the quality of outdoor air. PMID- 1511550 TI - Indoor air pollution. AB - This article summarizes the health effects of indoor air pollutants and the modalities available to control them. The pollutants discussed include active and passive exposure to tobacco smoke; combustion products of carbon monoxide; nitrogen dioxide; products of biofuels, including wood and coal; biologic agents leading to immune responses, such as house dust mites, cockroaches, fungi, animal dander, and urine; biologic agents associated with infection such as Legionella and tuberculosis; formaldehyde; and volatile organic compounds. An approach to assessing building-related illness and "tight building" syndrome is presented. Finally, the article reviews recent data on hospital-related asthma and exposures to potential respiratory hazards such as antineoplastic agents, anesthetic gases, and ethylene oxide. PMID- 1511551 TI - Asbestos exposure in buildings. AB - Asbestos-related diseases are dose-related. Among these, asbestosis has occurred only with the heavy exposures of the past, is a disappearing disease, and is of no concern with the very small exposures from building occupancy. A possibly increased incidence of lung cancer has been included in risk analysis, but probably is also related to high exposure in that both epidemiologic and experimental data suggest a link between the process of alveolar inflammation and fibrogenesis and carcinogenesis. The major concern has been mesothelioma in that it has occurred with much lower household and neighborhood exposure. Additionally, anxiety concerning buildings with ACM has been heightened by finding of friable asbestos in about 20% of public buildings, discovery of environmental asbestos fibers and asbestos bodies in autopsies, and demonstration of a linear relationship between exposure and lung cancer risk in occupational groups, inviting extrapolation to a much lower dose. Legislative and regulatory mandates, promotional activities of abatement companies, adverse court decisions placing the onus of repairs on asbestos manufacturers, and a "pandemic of mediagenic disease" all have contributed to panic among building owners, school boards, insurers, and others. In that there is neither clinical nor epidemiologic support for asbestos-related disease from building occupancy, risk estimates have been based on extrapolation from past experience with generally high-dose occupational exposure. However, only a few epidemiologic studies have contained quantitative estimates of exposure, and these have been measured in terms of all particles, with conversion to asbestos fibers uncertain and the fiber type and dimension largely unknown. To these uncertainties must be added the unproved assumption of a linear dose-response down to very low levels of exposure with no threshold. At the other end of the scale extrapolation has required measurements of present building exposure, and these have been revised downward as methods for collection and analysis have improved. Risk estimates in this country and abroad have assumed exposure to 0.001 f/mL, with indicated lifetime risks for cancer ranging from about 2 to 20 per 1 million students. However, these estimates have assumed mixed fiber exposure whereas most building exposure comes from chrysotile, which is much less toxic than the amphiboles.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1511552 TI - Coal workers' pneumoconiosis. AB - CWP is a disease distinct and separate from silicosis. Simple CWP is clearly related to the amount of dust deposited within the lungs. Complicated CWP (PMF) results from dust deposition plus other factors. Immunologic and local cellular factors may contribute to the development of this form of the disease. Studies of lung cell response and function may further elucidate mechanisms and mediators of lung dust reaction. Complicated CWP (PMF) is clearly associated with alterations in ventilatory, mechanical, and vascular function of the lungs. These abnormalities in PMF contribute to the observed premature morbidity and mortality of this disease. PMID- 1511553 TI - Silicosis. AB - Silicosis is an ancient disease, but with modern understanding of safe levels of exposure, it should be a vanishing disease. Emphasis will be placed on newer concepts in the pathogenesis of the disease and the health effects of low levels of quartz dust in relation to current exposure standards. The ongoing controversy regarding the carcinogenicity of quartz is discussed. PMID- 1511554 TI - The hard metal diseases. AB - Hard metal is a mixture of tungsten carbide and cobalt, to which small amounts of other metals may be added. It is widely used for industrial purposes whenever extreme hardness and high temperature resistance are needed, such as for cutting tools, oil well drilling bits, and jet engine exhaust ports. Cobalt is the component of hard metal that can be a health hazard. Respiratory diseases occur in workers exposed to cobalt--either in the production of hard metal, from machining hard metal parts, or from other sources. Adverse pulmonary reactions include asthma, hypersensitivity pneumonitis, and interstitial fibrosis. A peculiar, almost unique form of lung fibrosis, giant cell interstitial pneumonia, is closely linked with cobalt exposure. PMID- 1511555 TI - Hypersensitivity pneumonitis. AB - Hypersensitivity pneumonitis is a syndrome caused by sensitization to any of a wide variety of environmental antigens and results in a pulmonary immunologic inflammatory process. The clinical syndrome occurs in a temporal relationship to exposure to the offending agent with resultant systemic or respiratory symptoms with defined chest radiographic and pulmonary function abnormalities. Definitive immune responses include those of the humoral and cellular system. Avoidance of exposure as treatment results in reversal of the clinical abnormalities. PMID- 1511556 TI - Hazardous exposure and lung disease among farm workers. AB - Industrialization of farming, animal raising, and forestry has added new chemical and mechanical hazards that need to be recognized and prevented. Lung disease among farm workers can result from a wide variety of hazardous exposures that include organic dusts, chemicals, and toxic gases. In addition to nonspecific symptoms of mucous membrane irritation, farm workers can develop occupational asthma or bronchitis, organic dust toxic syndrome, hypersensitivity pneumonitis, silo filler's disease (toxic hemorrhagic pulmonary edema), and neuromuscular respiratory failure. PMID- 1511557 TI - Health effects of synthetic vitreous fibers. AB - This article reviews the terminology and manufacturing process for synthetic vitreous fibers. The in vitro and in vivo animal experimental data that correlate fiber toxicity with dose, dimensions, and durability are summarized. Occupational exposure data are presented as well as the potential irritant effects of synthetic vitreous fibers. The ongoing human morbidity and mortality studies are summarized along with current occupational exposure standards. The discussion correlates physical properties related to fiber toxicity and the types of synthetic vitreous fibers. PMID- 1511558 TI - Occupational lung cancer. AB - The Contribution of Occupational Exposures to Lung Cancer. The overall importance of occupational agents as a cause of lung cancer has been a controversial subject since the 1970s. A federal report, released in the late 1970s, projected a surprisingly high burden of occupational lung cancer; for asbestos and four other agents, from 61,000 to 98,000 cases annually were attributed to these agents alone. Many estimates followed, some much more conservative. For example, Doll and Peto estimated that 15% of lung cancer in men and 5% in women could be attributed to occupational exposures. A number of population-based case-control studies also provide relevant estimates. In a recent literature review, Vineis and Simonato cited attributable risk estimates for occupation and lung cancer that ranged from 4% to 40%; for asbestos alone, the estimates ranged from 1% to 5%. These estimates would be expected to vary across locations and over time. Nevertheless, these recent estimates indicate that occupation remains an important cause of lung cancer. Approaches to Prevention. Prevention of lung cancer mortality among workers exposed to agents or industrial processes that cause lung cancer may involve several strategies, including eliminating or reducing exposures, smoking cessation, screening, and chemo-prevention. For example, changes in industrial processes that have eliminated or reduced exposures to chloromethyl ethers and nickel compounds have provided evidence of reduced risk of lung cancer following these changes. Although occupational exposures are important causes of lung cancer, cigarette smoking is the most important preventable cause of lung cancer. For adults, the work site offers an important location to target smoking cessation efforts. In fact, the work site may be the only place to reach many smokers. As many as 70% of smokers participating in a work site program reported that they would not seek out other programs for smoking cessation. Furthermore, these programs may be as effective as other smoking cessation programs, with abstinence approaching 30%. By creating a supportive social environment, policies restricting smoking in the workplace may also assist smokers trying to quit. Screening of workers at high risk of lung cancer, with periodic chest radiography and sputum cytology, offers potential methods for early detection that may improve prognosis. However, the failure of those procedures to improve outcome from lung cancer among high-risk smokers makes screening of workers of doubtful value. Both epidemiologic and experimental evidence suggest that dietary factors may modify the risk of lung cancer. To date, attention has been focused on vitamin A and carotenoids.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1511559 TI - Pulmonary infections acquired in the workplace. A review of occupation-associated pneumonia. AB - The risk of humans acquiring pneumonia as a result of their occupation appears to have declined during the twentieth century in developed countries, such as the United States. Thus, some conditions that are traditionally associated with the workplace, such as woolsorters' disease, represent illnesses that are of historical interest only. Nevertheless, the problem of occupation-associated pneumonia remains substantial. First, large outbreaks of zoonotic infections continue to occur, especially psittacosis among poultry farmers and abattoir workers. Second, clusters of illnesses caused by recently recognized pathogens are now being reported, including legionnaires' disease in industrial workers and Chlamydia pneumoniae infections in military personnel. Finally, epidemics of old conditions are appearing in new settings, such as tuberculosis among nursing home workers. Thus, the transmission, control, and treatment of pneumonias acquired in the workplace represent intriguing and challenging areas of concern to the epidemiologist and clinician. PMID- 1511560 TI - Respiratory disability. The uncoupling of oxygen consumption and disability. AB - In the past it was believed that respiratory disability could be objectively assessed by comparing the measured O2 consumption requirement of the job with the subjects' measured or estimated maximal oxygen consumption. More recently, it has become clear that this "classic" paradigm does not completely apply to all situations. This article reviews recent aspects of respiratory disability assessment. PMID- 1511561 TI - Diabetes care progress report: shows promise, could do better. PMID- 1511562 TI - Facilities in diabetic clinics in the UK: how much have they changed? AB - Two postal questionnaire surveys of facilities and staff available to hospital physicians responsible for the care of adults with diabetes in the United Kingdom have been carried out under the auspices of the British Diabetic Association. These surveys, in 1982-83 and 1990, achieved 92% and 94% responses, respectively, giving information on around 95% of UK health districts or their equivalent. Levels of provision and the use of existing facilities had, in general, improved over that time though several important deficiencies still remain. Respondents providing out-of-hours clinics and combined clinics with other specialties increased as did the availability of dietetic advice in outpatient clinics. Although the proportion of respondents reporting no specialist diabetes nursing assistance fell from 53% to 14%, this still left 29 reporting none at all. Access to blood glucose and HbA1 results, facilities for retinal examination, and access to photocoagulation had all improved but there was little change in the availability of adequate examination and educational facilities although this may have been due to a rise in expectations. Chiropodial care was less readily available in 1990 with 17% of respondents (compared with 11%) reporting a complete lack in the clinic. A recommendation that no locality should be without at least one physician with a special interest in diabetes was fulfilled in 81.9% of localities but some were still relatively poorly staffed. PMID- 1511563 TI - Is insulin atherogenic? PMID- 1511564 TI - The effect of chronic hyperglycaemia on the islet B-cell responsiveness in newly diagnosed type 2 diabetes. AB - The aim of the present study was to evaluate the effect of chronic hyperglycaemia on the pancreatic B-cell response to stimulation with a standard mixed meal or intravenous glucagon in 7 subjects with newly diagnosed Type 2 diabetes. Stimulation was performed at mean chronic fasting hyperglycaemia of 11.8 +/- 0.7 (SEM) mmol l-1 and at normoglycaemia obtained by an intravenous infusion of regular insulin followed by an insulin wash-out period. The incremental plasma C peptide area under the curve after stimulation with the meal was similar at normo and hyperglycaemia. In contrast, prestimulatory plasma C-peptide and the incremental plasma C-peptide area under the curve after stimulation with glucagon were significantly higher at chronic hyperglycaemia than at normoglycaemia (p less than 0.01 and p less than 0.05). In conclusion, chronic hyperglycaemia as seen in newly diagnosed Type 2 diabetes is associated with a complete lack of potentiation of postprandial islet B-cell secretion but a partly preserved potentiation of basal and post-glucagon islet B-cell secretion. PMID- 1511565 TI - Peripheral glucose uptake and skeletal muscle GLUT4 content in man: effect of insulin and free fatty acids. AB - To investigate the relationship between glucose uptake and the content of the insulin regulatable glucose transporter, GLUT4, in skeletal muscle at near physiological insulin concentrations in vivo, we measured the effect of a 3h euglycemic insulin-infusion (40 mU m-2 min-1) on glucose uptake and skeletal muscle GLUT4 content in 10 healthy subjects. We found no correlation (r approximately 0.1) between individual muscle GLUT4 content and insulin-stimulated glucose uptake. Mean GLUT4 content in skeletal muscle was reduced by 19 +/- 6.3% (mean +/- SE, p less than 0.02) after insulin infusion. However, when the same subjects were made insulin resistant by infusion of lipid, as evidenced by a reduction of 16 +/- 7.2% (mean +/- SE, p less than 0.05), in insulin-stimulated glucose uptake, the effect of insulin on GLUT4 content was attenuated and no change in GLUT4 content was observed. Our results show that the total content of skeletal muscle GLUT4 is a poor predictor for in vivo response to near physiological insulin concentrations in healthy human subjects. PMID- 1511566 TI - The effect of acipimox in patients with type 2 diabetes and persistent hyperlipidaemia. AB - A placebo-controlled, double-blind study was performed to assess the effect of 12 weeks treatment with acipimox (250 mg three times per day) on lipoproteins and glycaemic control in patients with Type 2 diabetes. All patients studied had persistent hyperlipidaemia despite acceptable glycaemic control on treatment with diet alone or diet and oral hypoglycaemic agents, achieving glycosylated haemoglobin (HbA1) of less than 10.5% but with fasting total triglycerides greater than 2.5 mmol l-1 or total cholesterol greater than 6.5 mmol l-1. Forty eight patients were randomized to treatment, 21 to acipimox and 27 to placebo; 43 completed the trial. All patients had been diabetic for at least 1 year. Total cholesterol fell by 6% and total triglycerides by 19% following 12 weeks of acipimox, compared to rises in the placebo group of 1% and 16%, respectively (p less than 0.05). There were no significant differences between acipimox and placebo in the change in low density lipoprotein (LDL) cholesterol, high density lipoprotein (HDL) cholesterol, apolipoproteins AI, AII, or B, or in glycaemic control during the treatment period. Acipimox is effective in reducing fasting total cholesterol and total triglycerides in patients with Type 2 diabetes with acceptable blood glucose control but persistent hyperlipidaemia. Acipimox does not adversely affect glucose tolerance. PMID- 1511567 TI - Conventional and sprinkler needle injection of magnesium insulin. AB - Currently available short-acting insulin preparations fail to mimic the postprandial insulin profile of non-diabetic individuals. The activity of a novel insulin designed for faster absorption has been tested after subcutaneous injection. Magnesium insulin (50 U ml-1) given by sprinkler needle was compared with unmodified human insulin (100 U ml-1) given by conventional needle and unmodified human insulin (50 U ml-1) given by sprinkler needle in normal volunteers using a euglycaemic clamp. Magnesium insulin had a significantly faster onset of action resulting in a higher exogenous insulin level by 15 min, peak level was reached after 60 min compared with 75 min for the unmodified insulins, and duration of action was significantly shorter than both unmodified insulins. No significant differences were observed between the unmodified insulins for the first 5 h after injection, indicating that the observed differences to magnesium insulin could not be attributed to the insulin concentration or the type of needle used for insulin administration. Injection of magnesium insulin prior to a test breakfast in people with Type 2 diabetes resulted in significantly lower total and 0 to 120 min areas under the glucose curve, an earlier rise in exogenous insulin levels and a higher area under the insulin curve from 0 to 120 min compared with unmodified 100 U ml-1 human insulin. PMID- 1511568 TI - Differential effects of near-normoglycaemia for 4 years on somatic nerve dysfunction and heart rate variation in type 1 diabetic patients. AB - To evaluate the long-term effects of near-normoglycaemia on somatosensory and autonomic nerve dysfunction, 55 poorly controlled Type 1 diabetic patients were allocated to intensified insulin treatment using continuous subcutaneous insulin infusion or multiple insulin injections and were studied prospectively for 48 months. They were divided into three groups according to their mean HbA1 levels during the study. Group 1 (n = 19) had mean HbA1 during months 3-48 in the normal range of less than 7.8% (near-normoglycaemic control), Group 2 (n = 18) showed moderately elevated mean HbA1 between 7.8 and 8.5% (satisfactory control), and Group 3 (n = 18) had clearly elevated mean HbA1 of greater than or equal to 8.6% (poor control). In the three groups studied, the changes in nerve conduction over baseline in the median and peroneal motor nerves as well as median and ulnar sensory nerves after 4 years were inversely related to the mean HbA1 levels of months 3-48 (all p less than 0.05). No significant associations with mean HbA1 were noted for the ulnar motor and sural sensory nerve conduction, vibration perception threshold, and heart rate variation. The percentages of patients with neuropathic symptoms decreased from 32 to 14% in Group 1, remained fairly constant in Group 2, and increased from 41 to 73% in Group 3 after 48 months when compared to baseline (p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1511569 TI - The effect of insulin infusion on capillary blood flow in the diabetic neuropathic foot. AB - The effect of a short-term improvement in glycaemic control induced by insulin infusion on foot skin capillary blood flow was previously unknown. In seven Type 2 (non-insulin-dependent) diabetic subjects with neuropathy capillary blood flow was measured in the great toe nailfold by television microscopy. An estimate of arteriovenous shunt flow was obtained simultaneously in the pulp of the great toe by laser Doppler flowmetry. After omission of oral hypoglycaemic therapy for 24 h mean blood glucose was 15.7 +/- 0.7 (SEM) mmol l-1. A priming infusion of 0.1 U kg-1 of insulin was given intravenously over 15 min, followed by a variable rate insulin infusion adjusted to steadily reduce blood glucose avoiding hypoglycaemia. At the end of the study blood glucose was reduced to 6.9 +/- 0.7 mmol l-1 (p less than 0.001). During the insulin infusion, capillary blood velocity increased by 28.8% (p less than 0.05), and the diameter of the capillary erythrocyte column increased from 7.6 +/- 0.2 to 9.2 +/- 0.3 micron (p less than 0.01). Thus during the insulin infusion, the calculated capillary flow increased to 226 +/- 36% above basal values (p less than 0.01). Laser Doppler flow did not change significantly, suggesting that during insulin infusion skin blood flow is redistributed with an increase in capillary flow relative to arteriovenous shunt flow. PMID- 1511570 TI - Does increased glomerular filtration rate or disturbed tubular function early in the course of childhood type 1 diabetes predict the development of nephropathy? AB - To clarify whether glomerular hyperfiltration or disturbances in renal tubular function may be early markers of the later development of nephropathy a follow-up study was performed in 34 young Type 1 diabetic patients, who had originally been investigated 12 years previously. The initial median age was 14 (range 7-18) years and median diabetes duration 7 (2-14) years. At initial examination only one of the 34 diabetic patients exhibited increased urinary albumin excretion rate. The median glomerular filtration rate was increased (136 vs 107 ml min-1 1.73 m-2; p less than 0.0001) and median threshold concentration of phosphate per litre of glomerular filtrate was decreased (1.27 vs 1.76 mmol l-1; p less than 0.0001) in the diabetic group as compared to that of 28 healthy children. At follow-up 17 patients showed increased urinary albumin excretion rate and the median glomerular filtration rate in this group was significantly lower than that of 17 patients with normal urinary albumin excretion rate (108 vs 125 ml min-1 1.73 m-2; p less than 0.05). However, no relationships were found between the increased urinary albumin excretion (incipient and/or overt diabetic nephropathy) at follow-up to either the initial glomerular filtration rate (134 vs 137 ml min 1 1.73 m-2; p greater than 0.05) or to renal tubular function assessed from urinary excretion rate of beta 2-microglobulin (0.059 vs 0.069 microgram min-1; p greater than 0.05) and the renal threshold concentration of phosphate per litre of glomerular filtrate (1.29 vs 1.22 mmol l-1; p greater than 0.05). PMID- 1511571 TI - Increased incidence of end-stage renal failure secondary to diabetes mellitus in Asian ethnic groups in the United Kingdom. AB - Diabetic renal disease is more common in patients of Asian ethnic origin than White Caucasians in the United Kingdom. This study determines whether a disparity in the incidence of end-stage renal failure secondary to diabetes mellitus exists between these ethnic groups. The incidence of treated end-stage renal failure was estimated using the person-time at risk incidence rate for patients receiving renal replacement therapy secondary to diabetes mellitus in the county of Leicestershire from 1979 to 1988. The incidence rate of end-stage renal failure expressed for the estimated population of patients with diabetes mellitus in patients of Asian ethnic origin was 486.6 (95% CI, 185.1 to 788.1) cases per million person-years per year, compared to 35.6 (17 to 54.2) in White Caucasians. All patients of Asian ethnic origin developing end-stage renal failure had non insulin-dependent diabetes. The high incidence of end-stage renal failure secondary to diabetes mellitus in patients of Asian ethnic origin in the UK imparts significant public health implications for resource planning and allocation, and the need to initiate strategies to ameliorate renal disease in this ethnic group. PMID- 1511572 TI - Morbidity, mortality, and albuminuria in type 2 diabetic patients: a three-year prospective study of a random cohort in general practice. AB - In a 3-year prospective study, the prevalence of albuminuria and its relationship to macrovascular disease, pre-existing vascular risk factors and mortality rate were studied in a random cohort of 290 patients with Type 2 diabetes mellitus in general practice. Newly occurring micro- or macroalbuminuria was associated with significantly (p less than 0.05) higher systolic blood pressure: median (IQ range) 157 (140-170) vs 150 (130-160) mmHg, in addition to higher serum triglycerides: median (IQ range) 2.71 (1.84-4.25) vs 1.84 (1.35-3.14) mmol l-1, and C-peptide levels: median (IQ range) 1.30 (0.98-2.16) vs 1.10 (0.82-1.58) nmol l-1, at 3-year follow-up. Patients with macroalbuminuria at final examination had significantly higher systolic and diastolic blood pressure, serum triglyceride and beta 2-microglobulin levels, decreased HDL-cholesterol, and a significantly higher prevalence of carotid artery stenoses and peripheral vascular disease. Patients dying from vascular causes showed significantly higher urinary albumin levels at entrance as compared to the surviving patients: median (IQ range): 42.2 (11-249.7) vs 10.4 (4.6-28.0) mg l-1, p less than 0.008, and overall mortality rate was significantly linked with the presence of macroalbuminuria (26% vs 5% in normoalbuminuric patients). A comparison between the results of the initial and the final examination indicated an overall worsening of renal variables (albuminuria: median (IQ range): female 9.5 (4.5-21) vs 13.4 (5.1-39.7) mg l-1, (p less than 0.05); male 13.8 (4.7-34.1) vs 32.6 (8.1-78.7) (p less than 0.001), despite a significant improvement in metabolic variables.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1511573 TI - Clinical and metabolic characteristics of type 1 and type 2 diabetes: an epidemiological study from the Narpes community in western Finland. AB - Clinical and metabolic characteristics of all known Type 1 and Type 2 diabetic patients in a well-defined area in Western Finland are described. Retrospective data from the time of diagnosis and follow-up data were examined. Overall prevalence of diabetes was 25.4 cases per 1000 population. Patients were defined as having Type 1 or Type 2 diabetes based upon early insulin requirement and C peptide levels. Applying these criteria 84% of the patients had Type 2 diabetes. Onset before the age of 40 years was observed in only 3% of Type 2 diabetic patients. This age limit therefore had a sensitivity of 97% and a specificity of 90% in correctly predicting Type 2 diabetes. At diagnosis, hypertension was observed in 2% of Type 1 and in 75% of Type 2 diabetic patients; the corresponding numbers at follow-up were 6 and 63%. At investigation, 27% of Type 1 and 22% of Type 2 diabetic patients had microalbuminuria. Retinopathy was observed in only 12% of Type 2 compared with 54% of Type 1 diabetic patients. The presence of retinopathy was associated with longer diabetes duration both among Type 1 and Type 2 diabetic patients. A significant decrease in C-peptide concentration was observed in Type 2 diabetic patients with increasing diabetes duration. The data therefore suggest that Type 2 diabetes is associated with a deterioration of beta-cell function with time. PMID- 1511574 TI - Education and employment experiences in young adults with type 1 diabetes mellitus. AB - Educational attainment, employment experiences, and self-esteem were measured using semi-structured questionnaires in young adults with Type 1 diabetes mellitus and in a group of age/sex matched healthy controls. Results showed that subjects with diabetes and their matched controls obtained comparable qualifications at all levels. However, subjects with diabetes were less likely to feel competent with regard to their educational performance, and many of this group reported experiencing difficulties at school. There were no differences in the proportion of each group who had experienced unemployment, although this was explained more by social class and educational attainment. Whereas only a minority had decided to withhold information about their condition from their employers, one-third of those with diabetes had experienced health-related problems in obtaining employment. This study suggests that the educational achievements and employment experiences of young adults with diabetes may not differ from those of healthy controls. However subjective reports of difficulties in these areas may be associated with reduced self-esteem. Confirmation of these findings should be carried out in a larger sample, using a prospective design. PMID- 1511575 TI - Brittle diabetes: a report of the First International Conference on Brittle Diabetes. PMID- 1511576 TI - A party of 43 young people with diabetes go skiing. PMID- 1511577 TI - Teacher training and children with type 1 diabetes. PMID- 1511578 TI - The role of adult physicians in the care of diabetic adolescents. PMID- 1511579 TI - Use of a family record in diabetes clinics. AB - As a result of a two-year study funded by a BDA Diabetes Development Project, data are presented on the usefulness of a family record in paediatric diabetes clinics. There was a poor response to the invitation to try the family record. Examples are given of its potential usefulness but it is acknowledged that it is likely to be more useful if a psychiatrist or psychotherapist is part of the team. PMID- 1511580 TI - Toenail surgery for diabetic patients. PMID- 1511581 TI - Pen injectors--the way forward? PMID- 1511582 TI - Facilitation of diabetes care in North Tyneside. PMID- 1511583 TI - Varieties of numerical abilities. AB - This paper provides a tutorial introduction to numerical cognition, with a review of essential findings and current points of debate. A tacit hypothesis in cognitive arithmetic is that numerical abilities derive from human linguistic competence. One aim of this special issue is to confront this hypothesis with current knowledge of number representations in animals, infants, normal and gifted adults, and brain-lesioned patients. First, the historical evolution of number notations is presented, together with the mental processes for calculating and transcoding from one notation to another. While these domains are well described by formal symbol-processing models, this paper argues that such is not the case for two other domains of numerical competence: quantification and approximation. The evidence for counting, subitizing and numerosity estimation in infants, children, adults and animals is critically examined. Data are also presented which suggest a specialization for processing approximate numerical quantities in animals and humans. A synthesis of these findings is proposed in the form of a triple-code model, which assumes that numbers are mentally manipulated in an arabic, verbal or analogical magnitude code depending on the requested mental operation. Only the analogical magnitude representation seems available to animals and preverbal infants. PMID- 1511584 TI - Cognitive mechanisms in numerical processing: evidence from acquired dyscalculia. AB - This article discusses cognitive neuropsychological research on acquired dyscalculia (i.e., impaired numerical processing resulting from brain damage), surveying issues of current interest, and illustrating the ways in which analyses of acquired deficits can contribute to an understanding of normal processing. I first review the logic whereby inferences concerning normal cognition are drawn from patterns of impaired performance. I then consider research exploring the general functional architecture of the cognitive numerical processing mechanisms, and finally turn to studies aimed at probing the internal structure and functioning of individual processing components. PMID- 1511585 TI - Images of numbers, or "When 98 is upper left and 6 sky blue". AB - Some people declare that they possess a personal visual representation of numbers: some automatically "see" the numbers they are confronted with in a precise location in a structured mental space, others "associate" specific colours with given numbers. Such visuo-spatial representations of numbers were first described by Galton in 1880 but have since received little attention from psychologists. It is the aim of this article to describe these mental representations and discuss their role in number processing. The authors first review Galton's observations, and then present their own. Finally, they discuss the relevance of these visuo-spatial representations in relation to contemporary debates on number representation and calculation. PMID- 1511586 TI - Preverbal and verbal counting and computation. AB - We describe the preverbal system of counting and arithmetic reasoning revealed by experiments on numerical representations in animals. In this system, numerosities are represented by magnitudes, which are rapidly but inaccurately generated by the Meck and Church (1983) preverbal counting mechanism. We suggest the following. (1) The preverbal counting mechanism is the source of the implicit principles that guide the acquisition of verbal counting. (2) The preverbal system of arithmetic computation provides the framework for the assimilation of the verbal system. (3) Learning to count involves, in part, learning a mapping from the preverbal numerical magnitudes to the verbal and written number symbols and the inverse mappings from these symbols to the preverbal magnitudes. (4) Subitizing is the use of the preverbal counting process and the mapping from the resulting magnitudes to number words in order to generate rapidly the number words for small numerosities. (5) The retrieval of the number facts, which plays a central role in verbal computation, is mediated via the inverse mappings from verbal and written numbers to the preverbal magnitudes and the use of these magnitudes to find the appropriate cells in tabular arrangements of the answers. (6) This model of the fact retrieval process accounts for the salient features of the reaction time differences and error patterns revealed by experiments on mental arithmetic. (7) The application of verbal and written computational algorithms goes on in parallel with, and is to some extent guided by, preverbal computations, both in the child and in the adult. PMID- 1511587 TI - Cognitive arithmetic: a review of data and theory. AB - The area of cognitive arithmetic is concerned with the mental representation of number and arithmetic, and the processes and procedures that access and use this knowledge. In this article, I provide a tutorial review of the area, first discussing the four basic empirical effects that characterize the evidence on cognitive arithmetic: the effects of problem size or difficulty, errors, relatedness, and strategies of processing. I then review three current models of simple arithmetic processing and the empirical reports that support or challenge their explanations. The third section of the review discusses the relationship between basic fact retrieval and a rule-based component or system, and considers current evidence and proposals on the overall architecture of the cognitive arithmetic system. The review concludes with a final set of speculations about the all-pervasive problem difficulty effect, still a central puzzle in the field. PMID- 1511588 TI - Treatment of carcinoma of the prostate in the 1990's. PMID- 1511589 TI - Hopkins researchers close in on cause of Lou Gehrig's disease. PMID- 1511590 TI - Predictor of survival for colorectal cancer patients identified. PMID- 1511591 TI - The current status of radiolabeled monoclonal antibodies for the diagnosis and treatment of human malignancies. PMID- 1511592 TI - Adenocarcinoma of stomach: changing concepts in pathogenesis and therapy. PMID- 1511593 TI - Performance of a diagnostic system (Iliad) as a tool for quality assurance. AB - Quality assurance improves health care through detection of quality problems and feedback to the care giver. Current review procedures employed by the Peer Review Organizations (PROs), however, appear to underdetect quality problems, particularly those arising from diagnostic errors. We studied the use of an expert diagnostic system, Iliad, to detect quality problems arising from diagnostic errors. One hundred cases were selected from among those Medicare cases reviewed by the Utah PRO (UPRO) and which contained diagnoses recognized by Iliad. Iliad flagged 28 cases out of the 100 as containing diagnostic errors, and a gold standard physician review confirmed quality problems in 17 cases (60.7%). The UPRO review found 28 cases with quality problems, mostly treatment and documentation errors. The quality problems detected by Iliad appeared to be more serious than those detected by the UPRO review. Among the six cases with quality problems detected by both the UPRO and the Iliad review, there was none for which the same quality problem was detected by the two procedures. The two review procedures were therefore complementary. PMID- 1511594 TI - Representation of preferences in decision-support systems. AB - The recommendations of computer-based decision-support systems depend on the preferences of the expert who is responsible for the decisions. Often, these preferences are only represented implicitly, rather than explicitly, in the system. Decision-theoretic preference models that explicitly represent the preferences of the decision maker provide numerous advantages for decision support systems. In this paper, we describe these advantages. The creation and refinement of decision-theoretic preference models, however, is a difficult task. We describe an accurate and efficient method for determining the preferences of domain experts and refining the model that captures those preferences. In this preference assessment method, we simulate familiar decisions in the expert's area of expertise. We then infer the preferences of the expert from the choices that the expert makes on the simulated decisions, and use the preference information to refine the model automatically. PMID- 1511595 TI - Evaluation of a Meta-1-based automatic indexing method for medical documents. AB - This paper describes MetaIndex, an automatic indexing program that creates symbolic representations of documents for the purpose of document retrieval. MetaIndex uses a simple transition network parser to recognize a language that is derived from the set of main concepts in the Unified Medical Language System Metathesaurus (Meta-1). MetaIndex uses a hierarchy of medical concepts, also derived from Meta-1, to represent the content of documents. The goal of this approach is to improve document retrieval performance by better representation of documents. An evaluation method is described, and the performance of MetaIndex on the task of indexing the Slice of Life medical image collection is reported. PMID- 1511596 TI - A specialized framework for medical diagnostic knowledge-based systems. AB - For a knowledge-based system (KBS) to exhibit an intelligent behavior, it must be endowed with knowledge enabling it to represent the expert's strategies. The elicitation task is inherently difficult for strategic knowledge, because strategy is often tacit, and, even when it has been made explicit, it is not an easy task to describe it in a form which may be directly translated and implemented into a program. This paper describes a Specialized Framework for Medical Diagnostic Knowledge-Based Systems that can help an expert in the process of building KBSs in a medical domain. The framework is based on an epistemological model of diagnostic reasoning which has proven to be helpful in describing the diagnostic process in terms of the tasks that it is composed of. It allows a straightforward modeling of diagnostic reasoning at the knowledge level by the domain expert, thus helping to convey domain-dependent strategies into the target KBS. PMID- 1511597 TI - Analysis of physician questions in an ambulatory care setting. AB - We collected 69 questions generated by physicians based on their active patient medical records. Each question was associated with a single term in a specific record (Key Term). These questions were analyzed with respect to word content and concept content. Concepts were matched to the National Library of Medicine's Metathesaurus (Meta-1). Sixty-eight Key Terms were completely matched by Meta-1 terms. Each question matched to an average of 3.7 Meta-1 terms for a total of 255 concepts. Based on word count, these 255 concepts accounted for 43%, stop words accounted for 36%, and numbers and drug trade names accounted for 3% of the words. The remaining 18% of the words could be matched to 143 concepts not in Meta-1. Review of all concepts showed that they could be divided into medical terms (Noun Concepts), modifiers (Modifier Concepts), and concepts that provided context for the questions (Relation Concepts). The majority of Relation Concepts did not match concepts in Meta-1. A vocabulary of Relation Concepts would provide a useful starting point for a computer system designed to aid physicians in answering these questions. PMID- 1511598 TI - Ranking radiotherapy treatment plans using decision-analytic and heuristic techniques. AB - Radiotherapy treatment optimization is done by generating a set of tentative treatment plans, evaluating them, and selecting the plan closest to achieving a set of conflicting treatment objectives. The evaluation of potential plans involves making trade-offs among competing possible outcomes. Multiattribute decision theory provides a framework for specifying such trade-offs and using them to select optimal actions. Using these concepts, we have developed a plan ranking model which ranks a set of tentative treatment plans from best to worst. Heuristics are used to refine this model so that it reflects the clinical condition of the patient being treated and the practice preference of the physician prescribing the treatment. A figure of merit is computed for each tentative plan and is used to rank the plans. The approach described is very general and can be used for other medical domains having similar characteristics. The figure of merit can also be used as an objective function by computer programs that attempt to automatically generate an optimal treatment plan. PMID- 1511599 TI - LMSMVE: a program for least median of squares regression and robust distances. AB - The program LMSMVE performs robust regression analysis by using the method of the least median of squares. It also computes robust distances to locate leverage points, that is, outliers with respect to the set of independent variables. LMSMVE constructs plots of least median of squares residuals against robust distances. Both methods can tolerate up to half the data being outliers before they fail to give results that describe the bulk of the data. A complete system that operates directly on SYSTAT files is available for the IBM PC and compatibles; it includes a utility that converts ASCII files to SYSTAT format. PMID- 1511600 TI - Automated lanes detection and comparison of bacterial electrophoretic protein fingerprints using fast Fourier transformation. AB - A method of computer-automated analysis of bacterial fingerprints produced by electrophoresis of proteins in a one-dimensional slab gel system is described. Proteins were visualized by silver staining. Western blotting, or autoradiography. Gels were recorded with a CCD camera, and after initial manual removal of the unwanted image margins, track margins were identified and extracted and a normalized trace was produced automatically using Fourier routines to smooth plots required for this process. Normalized traces were then compared by Fourier correlation after application of a high-pass step filter. PMID- 1511601 TI - Analysis of beat-to-beat cardiovascular hemodynamic variables obtained from long term biotelemetry. AB - Manual methods of large volume data storage, retrieval, and analysis are difficult, time consuming, and present numerous opportunities for calculation errors. We have designed and implemented a comprehensive computer-based system for performing these functions. Development of this system was necessary since left ventricular (LV) blood pressure and two regional LV wall thickness measurements were obtained during long-term extracorporeal biotelemetry of miniswine for 24-h periods. During a single recording period over 100,000 individual cardiac cycles were recorded on analog tape and later analysed for determination of global myocardial oxygen demand and regional myocardial function. In addition, custom designed software was developed to determine the extent and duration of myocardial dysfunction. Batch file commands enabled the customized software to operate without prompting by the user thus optimizing the time usage of the computer, and the computer based data acquisition and analysis system. Although this system was designed specifically for analysing cardiovascular hemodynamic variables, it is flexible and can be applied to other experimental applications. PMID- 1511602 TI - A combined one- and two-way analysis of variance microcomputer program. AB - A simple microcomputer program in BASIC is designed to compute both the one-way and two-way analysis of variance. The program is an interactive one and can be easily and promptly used for statistical analysis of biomedical data. The applicability of the program is illustrated by data obtained from the percutaneous absorption of dihydroergotamine into the excised skin of rabbits. PMID- 1511603 TI - Microcontroller-based system for collecting anaerobic blood samples from a running greyhound. AB - Many physiological variables change rapidly in the blood during sprint exercise. To characterize the dynamics and extent of these changes, blood samples must be obtained during exercise. We describe herein a portable, microcontroller-based system used to automatically obtain repeated, anaerobic, arterial blood samples from greyhounds before, during, and following a race on a track. In addition, the system also records the blood temperature in the pulmonary artery each time a blood sample is taken. The system has been tested for more than 2 years and has proven to be reliable and effective. PMID- 1511604 TI - A computer model of the kidney. AB - We developed a computer model of renal function that factors perfusion pressure, serum sodium, potassium, antidiuretic hormone and aldosterone concentrations to derive urine output, urinary sodium and urinary potassium excretion. The model implements Uttamsingh's (Uttamsingh, R.J., et al. Mathematical model of the human renal system. Med. Biol. Eng. Comput. 23 (1985) 525-536) analytical equations as an electrical circuit suitable for network analysis. This model is useful for studying the effects of renal blood flow and the humoral milieu on renal function in normal kidneys either as a stand-alone unit or in combination with other physiological electrical models. PMID- 1511605 TI - Simulation of compartmental models for kinetic data from a positron emission tomograph. AB - Linear compartmental models are used to describe the disposition of radio labelled compounds in regions of interest in the mammalian body, based on a time sequence of measurements from a positron emission tomograph (PET). In this paper we show how closed form solutions for the model equations have been incorporated into a computer program for simulation and parameter estimation. A typical PET data example is included to illustrate the implementation and compare the closed form method with a numerical ode solution method. PMID- 1511606 TI - Development of an expert system advisor for anaesthetic control. AB - A review is given of numerous approaches which have been taken to provide automated control of depth of anaesthesia. Most of these approaches use a single indicator for anaesthetic state, and do not perform adequately for such a complex system. It is desirable, therefore, to merge a number of qualitative clinical signs and quantitative on-line measurements to provide decision-support for control of anaesthetic depth. The paper describes such an expert system called Resac (Real time Expert System for Advice and Control). Details of the knowledge representation and inference structure are given, together with the method adopted for propagating uncertainty measures, combining fuzzy information and merging quantitative and qualitative indicators. The importance of good human machine interface design is shown via the GEM-based graphics of Resac. PMID- 1511607 TI - Changes in serum levels of SHBG, endogenous ligands and levonorgestrel induced by ethinylestradiol in Norplant users. AB - This work was done in search for a model to examine target organ response to fluctuations in serum levels of sex hormone-binding globulin (SHBG) and its ligands. The time course and magnitude of fluctuations of SHBG, levonorgestrel (L Ng), estradiol (E2), testosterone (T) and dihydrotestosterone (DHT) in serum were examined during and after treatment with 50 ug of ethinylestradiol (EE2) daily for 10 days in 10 volunteer women using NORPLANT implants. Six of these volunteers were also treated with 20 ug of EE2 daily for 7 days and two additional volunteers using a copper-T IUD were treated with 50 ug of EE2 daily for 7 days. In all cases, SHBG and L-Ng levels increased in a close parallel manner several-fold above basal levels during treatment, reaching a maximum around two days after the last EE2 pill. In contrast, the levels of E2 and T increased in one subject, decreased in 5 and remained unchanged in 4, while changes of DHT were unrelated to those of the other ligands. Since the L-Ng "secretion rate" by NORPLANT implants is constant, it follows that the effect of EE2 on its levels is due to a decreased metabolic clearance rate, most likely secondary to the increased binding of L-Ng to SHBG in serum. This interpretation is in agreement with the close parallelism in the fluctuations of L-Ng and SHBG. It is concluded that in NORPLANT users, SHBG and L-Ng, but not the endogenous ligands, behave in a predictable manner in response to EE2. Thus, this model affords the possibility of exploring the influence of SHBG on tissue response to progestins. PMID- 1511608 TI - Cervical softening with mifepristone (RU 486) after pretreatment with naproxen. A double-blind randomized study. AB - Pretreatment with the progesterone antagonist mifepristone reduces the stiffness and facilitates mechanical dilatation of the uterine cervix. We studied the influence of the cyclo-oxygenase inhibitor naproxen on the softening effect of mifepristone on the cervix in thirty nulliparae. The patients were randomly allocated to receive 500 mg naproxen (group A) or placebo (group B) orally 60, 48, 36, 24 and 12 hours prior to vacuum aspiration. All patients received 100 mg mifepristone 48 and 36 hours before surgery. We found that the cervical softening effect of mifepristone was not antagonized by naproxen. The study indicates that the effect of mifepristone on the early pregnant cervix is not mediated through an increased production of prostaglandins. PMID- 1511609 TI - Effects of the prostanoid receptor antagonist, di-4-phloretin phosphate, upon human sperm motility. AB - The inhibitory effects of the prostanoid receptor antagonist, di-4-phloretin phosphate (DPP), upon washed human sperm motility were determined in vitro (up to 60 min of incubation). Concentrations tested were: 0.001, 0.01, 0.1, 0.25, 0.5, 2.5, 5.0 and 10.0 mM. All concentrations of DPP investigated caused cessation of sperm movement (percentage motility and average forward velocity) and the antimotility effect was essentially irreversible. The concentrations producing 50% inhibition were: percentage motility--1.31 +/- 0.56 mM (mean +/- SEM) and average forward velocity--1.95 +/- 0.68 mM. The mode of antimotility action appears to be multi-faceted. At high (10 mM) and intermediate (2.5 mM) concentrations, changes in fluidity of sperm plasmalemma (hypoosmotic swelling test) and loss of viability (nigrosin-eosin stain technique) constitute the primary means by which motility was disrupted. In contrast, these two parameters of motility remained unaltered at a lower concentration (0.25 mM) of DPP, and the mechanism precipitating the antimotility effect may involve mobilization of stored calcium ions and modulation of cyclic AMP levels. PMID- 1511611 TI - Intrahepatic cholestasis: a review of biochemical-pathological mechanisms. AB - Intrahepatic cholestasis involves impaired excretion of bile via the hepatobiliary system as a consequence of one or more lesions within the liver. In humans, intrahepatic cholestasis most often results as a side-effect of drug therapy and the clinical manifestation of this condition, jaundice, has been estimated to account for hospitalization in 2 to 5% of the cases for the general population and approaches as much as 20% in the elderly. With the aging of the population and the common occurrence of poly-drug therapy in geriatric patients, it is to be expected that jaundice due to drug-induced intrahepatic cholestasis will become even more prevalent, and accordingly the need to understand the basic mechanisms of this disease condition will become more urgent. The list of culprit agents implicated in the induction of intrahepatic cholestasis in humans is continually expanding. These include various steroid hormones, bile acids, drugs and other chemicals. Experimentally, a wide spectrum of agents has been shown to precipitate intrahepatic cholestasis. Over the years, a number of hypotheses on the biochemical and pathological mechanisms of intrahepatic cholestasis has emerged, including the following: impaired sinusoidal membrane function; interference with the distribution and binding of cytoplasmic endogenous carrier proteins; interference with mitochondrial energy supply; defects in the canalicular membrane including altered Na+/K+ -ATP-ase activity; impairment of microfilament and microtubule functions; interference with bile secretion involving bile acid dependent and independent fractions, and altered bile acid metabolism due to "hypoactive hypertrophic smooth endoplasmic reticulum". In partial agreement with the latter hypothesis, our studies indicated that impairment of the endoplasmic reticulum might represent one of the early stages in the development of intrahepatic cholestasis. Various experimental conditions that induce intrahepatic cholestasis to different degrees resulted in an interference of the synthesis of microsomal phospholipids and altered microsomal function. The conditions included the administration of various hepatotoxic compounds or steroids, pregnancy, delayed development of the endoplasmic reticulum in neonates, and dietary methyl donor or choline deficiency. This review reports the biochemical-pathological mechanisms postulated to be involved in the genesis of intrahepatic cholestasis with specific reference to experimental models of drug-induced intrahepatic cholestasis. The important practical implications of cholestasis are also briefly surveyed. PMID- 1511610 TI - Effects of multiglycosides of Tripterygium wilfordii (GTW) on rat fertility and Leydig and Sertoli cells. AB - Primary cultures of rat Leydig and Sertoli cells were used to evaluate the direct effects of GTW on testicular cells and to compare these to the effects of gossypol acetate. Both GTW and gossypol acetate can affect the survival of Leydig and Sertoli cells. But Sertoli cells are much more sensitive than Leydig cells, either to gossypol acetate or GTW. Leydig and Sertoli cells all died when they were exposed to gossypol acetate or GTW at a dose of 3.0 micrograms/ml or 30 micrograms/ml, respectively, for 24 hours. The cell survival-time course demonstrated that the cell numbers were decreased after 2 hours, and especially so after 8 hours. No significant changes were observed in testosterone production in Leydig cells after 24 hours of exposure to 1.0-20 micrograms/ml GTW. The forward motility of epididymal spermatozoa was completely lost and fertility of rat was significantly inhibited after the treatment of GTW in vivo. It is concluded that GTW does affect the fertility of rat and viability of cultured rat Leydig and Sertoli cells. PMID- 1511612 TI - Diurnal effect on caffeine acetylation phenotyping: a preliminary report. AB - The present study examined whether caffeine acetylation phenotype could be altered by its time of administration. Caffeine was given orally to nine healthy subjects at 10 a.m. and 10 p.m. and acetylation phenotype was determined by measuring the major metabolites of caffeine in urine. The results showed that acetylation phenotypes determined in the day trial were not different from those determined during the night trial. PMID- 1511613 TI - Chlorpromazine enhancement of epirubicin cytotoxicity in vitro: effects on plasma membrane and DNA damage. AB - The frequently used antiemetic drug chlorpromazine has previously been shown to augment anthracycline-induced toxicity to cultured Chinese hamster fibroblasts measured by cloning /1/. We therefore tested the ability of chlorpromazine to affect the induction of plasma membrane and DNA damage by the anthracycline epirubicin. Plasma membrane damage was determined by the cells' ability to accumulate 86Rb after incubation with 10 mg/l epirubicin, and DNA damage was determined by measuring the amount of DNA precipitation after incubation with 25 mg/l epirubicin. The epirubicin-induced inhibition of 86Rb-accumulation as well as the enhancement of epirubicin-induced DNA damage were markedly enhanced in the presence of chlorpromazine. Chlorpromazine augmentation of epirubicin cytotoxicity, including plasma membrane and DNA damage, may be due to its calmodulin antagonistic action and related to the maintenance integrity. Further studies are justified to evaluate the effects of chlorpromazine influence on antineoplastic drug action in vitro and in vivo. PMID- 1511614 TI - Use of nitrates in ischemic heart disease. AB - The organic nitrates have remarkably diverse actions that are or should be beneficial in patients with ischemic heart disease. These drugs are effective in all the important ischemic syndromes. Preliminary data in patients with acute infarction suggest that the drugs may be truly cardioprotective, resulting in improved mortality. This review has not discussed the role of nitrates in congestive heart failure or LV dysfunction, a subject of great importance. The nitrates are useful adjunctive agents in these syndromes, and the two VeHfT trials support the concept that long-term nitrate administration, in conjunction with hydralazine, may favorably alter the natural history of heart failure. This cardioprotective effect is similar to that suggested for the post-MI patient. The data are not strong enough for definitive conclusions at this time. The clinical benefits of nitrates in decreasing subjective (angina) and objective indices of ischemia in stable and unstable angina, as well as limited data in asymptomatic myocardial ischemia, are unequivocal and are as favorable as those for beta blockers or calcium antagonists. Tolerance is an important problem that unfavorably influences the potential benefits of nitrate therapy. I believe that this problem can be avoided with well-designed dosing regimens. Current research into endothelial biology in health and disease has further supported a physiologic role for the organic nitrates in patients with ischemic heart disease. The nitrate-platelet story, while controversial, is promising and offers another positive rationale for nitrate administration. The concept of nitrates replenishing disordered EDRF release or action is an exciting one. Physicians should feel fortunate to have such a remarkable group of drugs available for their patients. PMID- 1511615 TI - Ear psoriasis. AB - Psoriasis of the ears occurs in approximately 18 percent of all patients at some time. Prevention by avoidance of picking and scratching and careful cleansing are helpful. Treatment with intralesional injection of triamcinolone acetonide is effective in patients resistant to other therapies. PMID- 1511616 TI - Trapshooter's stigma. AB - We report an unusual episode of friction dermatitis combined with residual scarring in a member of the United States trapshooting team. PMID- 1511617 TI - Cryogenic injury due to local application of a reusable cold compress. PMID- 1511618 TI - Mogul skier's palm: traumatic hypothenar ecchymosis. AB - A unique purpuric--golden lesion on the hypothenar eminence of each palm is described in a mogul skier. These painful lesions, resulting from vigorous repetitive pole planting in the "bumps" at a ski area, are postulated to represent a form of localized soft tissue injury. PMID- 1511619 TI - Athlete's nodules: sports-related connective tissue nevi of the collagen type (collagenomas). AB - Sports-related connective tissue nevi of the collagen type (collagenomas) have been referred to as athlete's nodules. Surfers, boxers, marbles players, and football players are some of the athletes in whom these lesions have been observed. The nodules can be found on the dorsal aspect of the feet, knees, or knuckles and can readily be differentiated from other conditions by either clinical history or microscopic features or both. Treatment options include conservative measures or surgical intervention. Recurrent trauma and friction to the involved location are likely causative factors. Although the ultrastructural pathogenesis remains to be established, changes in the molecular metabolism of collagen resulting in enhanced synthesis and/or accumulation of collagen may have a contributory role. PMID- 1511620 TI - Dermatologic stigmata in sports: weightlifting. PMID- 1511622 TI - Special issue: Sports dermatology. PMID- 1511621 TI - Herpes gladiatorum: a growing problem in sports medicine. AB - Herpes skin infections among wrestlers--called herpes gladiatorum--occur frequently among high school and college wrestlers nationwide. Contact with opponents with active herpes infections appears to be the strongest risk factor associated with acquisition of infection. Previously acquired antibody to herpes simplex virus 1 infection may offer some protection from acquiring this disease. Morbidity associated with this disease can be significant, and widespread efforts to educate participants in close contact sports, such as wrestling, are advocated as control measures. PMID- 1511623 TI - A dermatologic diary. Portrait of a practice. PMID- 1511624 TI - Sports-related allergic dermatitis. PMID- 1511625 TI - Seabather's eruption. PMID- 1511626 TI - Micronuclei induction in pike (Esox lucius) in Swedish lakes contaminated with radiocaesium. AB - Micronuclei frequency in fish from Swedish lakes with high concentrations of radiocaesium was investigated. The frequency of micronucleus induction in fish varied in different lakes but was not correlated with caesium concentrations. PMID- 1511627 TI - Interaction of androgens and prolactin on prostatic enzymes of the pyruvate malate cycle involved in lipogenesis in castrated mature monkey, Macaca radiata. AB - Effects of androgens, prolactin (Prl) and bromocriptine (Br) on the specific activities of prostatic (caudal and cranial) enzymes of the pyruvate-malate cycle were studied in castrated mature bonnet monkeys. Castration decreased the activity of NADP+ isocitrate dehydrogenase (ICDH), ATP citrate lyase, malate dehydrogenase (MDH), malic enzyme and fatty acid synthase (FAS). Administration of testosterone propionate (TP)/dihydrotestosterone (DHT) increased the activities of all these enzymes in both lobes. Malate dehydrogenase maintained normal activity. Prl also had a stimulatory effect on the enzymes and was further enhanced when Prl was given in combination with TP/DHT. Unlike Prl, bromocriptine treatment inhibited all the enzymes in both lobes. Thus, prolactin was found to have a direct as well as a synergistic effect with androgens on enzymes of the pyruvate-malate cycle in the prostate of castrated mature monkeys. PMID- 1511628 TI - Effect of cisplatin on lipid peroxidation in pig blood platelets. AB - The effect of cisplatin (cis-diamminedichloroplatinum II) on the activities of the blood platelet antioxidative enzymes (glutathione peroxidase, superoxide dismutase) as well as on the peroxidation of blood platelet lipids was investigated. Cisplatin was found to cause a significant inhibition of platelet free radical scavering enzyme activity and an increase of malonyldialdehyde levels in blood platelets incubated with cisplatin in vitro. PMID- 1511629 TI - Utilization of phytohaemagglutinin for in vivo karyological studies in teleost fish. AB - A simple technique is described for increasing the number of mitoses in circulating blood and in the kidney of teleost fish. This method employed phytohaemagglutinin-P solution, a T-like cell mitogen, which was injected (1 mg/100 g body wt) intraperitoneally, and 53 h later many blasts suitable for karyological studies, blocked in metaphase, were present both in the circulating blood and in the kidney. PMID- 1511630 TI - A comparison of a solid phase IRC assay and the PSIFT for detection of antibodies to platelets. AB - A rapid solid phase indicator red cells assay (IRCA) for detection of platelet antibodies was developed and its sensitivity compared with PSIFT. Platelets were attached to the surface of polystyrene microtitre plate wells by means of a sodium carbonate buffer and centrifugation. Uncovered areas were blocked by a gelatin blocking buffer. After serum incubation bound platelet-specific antibodies were made visible by anti-IgG-coated indicator red cells and a brief centrifugation. A positive result, meaning the presence of an anti-platelet antibody was indicated by red cell adherence over the reaction surface. In the absence of serum antibodies to platelets the indicator red cells formed a pellet. The IRCA showed a high sensitivity; the anti-platelet antibody Thrombocyte was detectable until a dilution of 1:1,600 whereas the same antibody in the PSIFT could only be detected until a dilution of 1:400. PMID- 1511631 TI - Effect of phorbol ester PMA and puromycin on the maturation of mouse oocytes. AB - The effect of phorbol myristate acetate (PMA) and puromycin (PU) on maturation divisions of mouse oocytes was investigated. PMA changed the morphology and function of the spindle in meiosis I. The spindle had a broad polar region and did not commence karyokinesis in the first maturation division. This persisted in 25% of spindles which were passive up to 30 h of maturation. Half of the oocytes with spindles blocked by PMA between 20 and 30 h of maturation became activated, and 25% of the initial pool underwent abortive karyokinesis consisting of segregation of several chromosomes of the metaphase plate. Cytological observation indicated that the presence of PMA interfered with the elongation of the spindle in anaphase. Under the condition of changed phosphorylation of maturation of proteins by PMA, a reversible interphase was induced by PU. Most of the nuclei induced by PU exhibited pronuclei. A new class of nuclei induced by PU with condensed chromatin and having no nucleoli is described. The mechanism and consequences of interference of PMA on anaphase are discussed. PMID- 1511632 TI - Penetration of fleroxacin into human and animal tissues. AB - Fleroxacin concentrations in human and rat tissues were determined by HPLC following extraction with dichloromethane:isopropanol. This method yielded a high recovery of more than 85%. In the investigated tissues the fleroxacin levels were equal to or higher than those concomitantly measured in plasma. The concentration ratios 'tissue/plasma' were 1.6-2.7 for lung, 1.9-2.1 for muscle, 1.1-1.9 for gynaecological tissues and 1.2 for bone. Only in the case of fat and lens/eye lower ratios of 0.05-0.5 were found. The actual measured fleroxacin concentrations in most tissues and in plasma were high. Following oral administration of the recommended therapeutic dose of 400 mg, once daily, peak concentrations of 5-6 mg/l were reached in human plasma at steady state. Even 24 h after drug intake the fleroxacin level was still approximately 1 mg/l and thus in the range of the MIC90 values of susceptible bacteria causative for many types of tissue infections. PMID- 1511633 TI - Detection of antimicrobial drugs with Bacillus subtilis strain ATCC 6633: an update. AB - Bacillus subtilis strain ATCC 6633 was examined for susceptibility to 30 additional antimicrobial drugs, the majority of which had been released during the 1980s. The data served to update previous findings with regard to the suitability of this assay strain for the detection of chemotherapeutic agents in fluid clinical specimens. PMID- 1511634 TI - Saperconazole: in vitro and in vivo anticandidal activity. AB - The in vitro activity of saperconazole against eight candidal species (81 strains) was determined and compared with fluconazole, Sch 39304 and amphotericin B. Using brain heart infusion broth with an inoculum of 10(4) CFU/ml, the MIC ranges (micrograms/ml) of saperconazole were: less than or equal to 0.015- greater than 32 for Candida albicans, less than or equal to 0.015-16 for C. tropicalis, less than or equal to 0.015-32 for C. glabrata, less than or equal to 0.015-32 for C. parapsilosis, less than or equal to 0.015-0.12 for C. guilliermondii and less than or equal to 0.015-0.06 for C. krusei. Saperconazole was the most active agent tested against Candida species. Saperconazole and 5 fluorocytosine combinations showed synergistic interactions against Candida species, and no antagonistic interaction was demonstrated. In a rat vaginal candidiasis infection model, saperconazole and fluconazole were equipotent producing 75-100% cures at levels of 0.016-0.25%, respectively, when dosed intravaginally. After single oral dosing, saperconazole was 5-fold more potent than fluconazole with an ED50 value of 0.53 mg/kg. These data demonstrate that saperconazole is effective in a rat vaginal candidiasis infection either with a single oral dose or by intravaginal treatment. PMID- 1511635 TI - In vivo postantibiotic effect of isepamicin and other aminoglycosides in a thigh infection model in neutropenic mice. AB - The object of this work is to study in neutropenic mice the in vivo postantibiotic effect (PAE) of isepamicin, a new aminoglycoside, gentamicin and netilmicin on Staphylococcus aureus and Escherichia coli and in vivo killing kinetics using two different schedules (A and B) of isepamicin and gentamicin administration against S. aureus: (A) at time zero and every hour up to the 7th or 9th hour and (B) two doses only, at time zero and at the end of the PAE. The PAE of the three aminoglycosides was long (3-5 h), showing that of isepamicin to be the largest, especially on S. aureus. Both A and B treatment models show the same effectiveness for the two tested drugs. These results support the idea that the major significance of the PAE is in its application to dosing regimens. PMID- 1511636 TI - Comparison of two cephalosporins in the surgical treatment of peritrochanteric fractures. PMID- 1511637 TI - Temperature influence on life table statistics of the chicken mite Dermanyssus gallinae (Acari: Dermanyssidae). AB - An age-specific life table for the chicken mite Dermanyssus gallinae (DeGeer, 1778) was based on various observations carried out at 25 degrees C. The generation time was calculated to be 16.8 days; the intrinsic rate of natural increase was 0.12 per day, and the net reproductive rate was 7.2. A nonlinear function was found satisfactory to describe the developmental rate of the different immature life-stages at temperatures below 40 degrees C. The stage specific survival of the immature life-stages was generally high between 10 and 37 degrees C, but decreased quickly outside this temperature range. Most of the eggs were laid during the first three weeks of the adult life. The proportion of surviving females rapidly decreases after moulting to the adult stage. At a temperature of 30 degrees C, the highest number of eggs (3 eggs per day) was laid. PMID- 1511638 TI - Regeneration of Haller's sensory organ in the tick Ixodes ricinus L. AB - Amputation of legs in nymphs of ticks, obtained from the first laboratory generation, resulted in regeneration of the legs after moulting to adults. Haller's sensory organ on the upper surface of each foreleg tarsus was significantly modified following regeneration. Haller's organ in non-amputated legs of the experimental ticks remained unchanged, being comparable to controls. Pored olfactory sensilla in the anterior pit, in a capsule and on a distal knoll usually increased in number, as well as grooved, thin and conical sensilla. Bordering gustatory and double-walled postcapsular sensilla either decreased or increased in number. All additional sensilla were consistent in their location. Form of the anterior pit and capsule's aperture also deeply changed after the regeneration. The authors distinguish this changes as atavistic. No correlation between changes in different parts of the organ were found. A phenomenon of induction was discovered in our study: if a distal part of tick's gnathosoma was amputated together with the left foreleg, Haller's organ in the right, untreated leg possessed the same changes after moulting as the regenerated organ in the previously amputated left foreleg. PMID- 1511639 TI - Accuracy of transrectal ultrasound in predicting pathologic stage of rectal cancer before and after preoperative radiation therapy. AB - Transrectal ultrasound (TRUS) and CT scan staging of rectal cancers before, and TRUS staging after, 45 Gy of irradiation were compared with the pathologic stage of the resected specimen in 19 patients. Accuracy of TRUS before and after irradiation, and of CT scan before irradiation, was 32 percent, 63 percent, and 53 percent, respectively. CT scan before and TRUS after irradiation predicted lymph node involvement in 79 percent and 68 percent of cases, respectively. Positive predictive value for lymph node involvement before irradiation was 60 percent for CT scan and 37.5 percent for TRUS; after irradiation, it was 50 percent for TRUS. Negative predictive value was 100 percent for CT scan and TRUS before radiation and 88 percent for TRUS after irradiation. Preoperative radiation therapy makes TRUS and CT scan less effective as staging techniques. The absence of lymph nodes on TRUS and CT scan before and after irradiation is reliable. PMID- 1511640 TI - Treatment of rectal prolapse in the elderly by perineal rectosigmoidectomy. AB - The results and complications of perineal rectosigmoidectomy for complete rectal prolapse in 114 patients have been reviewed. Most patients were elderly and high risk by virtue of other concurrent medical conditions. Fourteen patients (12 percent) developed significant postoperative complications. Hospital stay was short (median, four days). Ten patients were lost to follow-up. The remaining 104 patients were followed for 3 to 90 months. Eleven patients (10 percent) developed recurrent full-thickness rectal prolapse, six of them underwent repeat perineal rectosigmoidectomy. Sixty-seven patients had fecal incontinence prior to surgery. Eleven patients underwent concomitant levatoroplasty; 10 of them either improved or regained full continence of feces postoperatively. Twenty-six of the 56 patients who underwent perineal rectosigmoidectomy alone improved or regained full continence. Rectal prolapse can be successfully treated by perineal rectosigmoidectomy in elderly, high-risk patients with minimal morbidity. Levatoroplasty dramatically improves fecal incontinence occurring in association with rectal prolapse. PMID- 1511641 TI - Chronic fissure-in-ano: a randomized study comparing open and subcutaneous lateral internal sphincterotomy. AB - A prospective study comparing open and subcutaneous lateral internal sphincterotomy for chronic anal fissure was conducted. One hundred twelve patients were randomized to open (n = 54) or subcutaneous (n = 58) sphincterotomy. There was no significant difference in acute complications between the subcutaneous (8.6 percent) and open (7.4 percent) groups. Postoperative length of stay was significantly shorter for the subcutaneous group (1.7 +/- 0.2 days) than for the open group (2.3 +/- 0.1 days; P less than 0.001). Although the response rate to a pain questionnaire was less than 50 percent, the data suggest a lower level of postoperative pain in the subcutaneous group. Fissure healing was similar between the subcutaneous (96.6 percent) and open (94.4 percent) groups. We conclude that subcutaneous lateral internal sphincterotomy for chronic fissure-in-ano is effective and may result in significantly less postoperative discomfort, shorter postoperative lengths of stay, and a comparable rate of complications compared with the open technique. PMID- 1511642 TI - Prognostic significance of anastomotic recurrence from colorectal adenocarcinoma. AB - A retrospective analysis of the prognostic significance of anastomotic recurrence in 50 patients with colorectal adenocarcinoma was conducted from 1970 to 1987. All primary cancers were located above 10 cm from the anal verge. Forty anastomotic recurrences (80 percent) followed resection of sigmoid or proximal rectal tumors. The overall disease-free interval was 13 months, with 90 percent of recurrences diagnosed within 24 months of the primary resection. Forty-five recurrences (90 percent) were associated with synchronous or metachronous metastases. Overall median survival following the recurrence was 16 months--37 months if the anastomosis was the only recurrence site. Of five patients alive without evidence of disease, all were asymptomatic, and recurrence was confined to the anastomosis. In conclusion, anastomotic recurrence following resection of colorectal adenocarcinoma frequently heralds disseminated disease but can be potentially resected for cure if it is the only site in an otherwise asymptomatic patient. PMID- 1511643 TI - Functional results of coloanal anastomosis with reservoir. AB - Functional results in 33 patients who underwent a coloanal anastomosis with reservoir were prospectively evaluated three months after colostomy closure and later (16.2 +/- 5.7 months) and were compared with those of 36 healthy controls. We were unable to demonstrate any significant difference between patients and controls concerning frequency of stools, feeling of the need to defecate, continence of stools and flatus, differentiation between flatus and feces, urgency, and need to wear a protective pad. There was a statistically significant difference concerning the ability to evacuate, which was better in the control group (score = 1.03) than in the patients (score = 1.63) (P less than 0.001). These results suggest that coloanal anastomosis with reservoir provides nearly normal function except for the ability to evacuate. PMID- 1511644 TI - Relationship between clinical symptoms of anal incontinence and the results of anorectal manometry. AB - The aim of this work was to analyze clinical symptoms in light of anorectal manometry results. We compared the frequency of clinical symptoms in relation with the presence or absence of functional anomalies. Using this methodology, the following relationships may be suggested: the need to wear a pad, with a decreased resting pressure at the upper part of the anal canal; the inability to delay rectal evacuation, with decreased anal voluntary contraction; interference of incontinence with social activities, with decreased duration of anal voluntary contraction; urinary symptoms, with an increased threshold volume of rectal distention needed to elicit the rectoanal inhibitory reflex; and complete rectal prolapse, with reduced length of the anal canal. PMID- 1511645 TI - Crohn's disease and carcinoma: increasing justification for surveillance? AB - Carcinoma of the colon that arises in patients with Crohn's disease is being reported with increasing frequency. To help clarify the nature of this association, records of 25 patients with Crohn's disease and colorectal carcinoma seen from 1957 through 1989 were reviewed. One patient had leiomyosarcoma of the rectum, and two patients had the onset of Crohn's disease after the diagnosis and treatment of colorectal carcinoma. Therefore, 22 patients were available for complete retrospective analysis. The median age at diagnosis of Crohn's disease was 37 years (range, 15-67 years), and the median age at diagnosis of carcinoma was 54.5 years (range, 32-76 years). The median duration of symptoms preceding the discovery of colorectal carcinoma was 18.5 years (range, 0-32 years). Carcinoma arose in colonic segments with known Crohn's disease in 77 percent of patients, and six patients (27 percent) had associated colonic mucosal dysplasia. One lesion was classified as Dukes A, nine lesions were Dukes B, five lesions were Dukes C, and seven lesions were Dukes D. Patients with an onset of Crohn's disease before the age of 40 years had primarily Dukes C or D lesions and consequently poor survival. Most patients presented with nonspecific signs and symptoms, with nothing to distinguish the activity of the Crohn's disease from the presence of colorectal neoplasm. Younger patients with long-standing Crohn's disease should be considered for colonic surveillance to permit earlier diagnosis and treatment of potential colorectal carcinoma. PMID- 1511646 TI - Influence of loperamide and loperamide oxide on the anal sphincter. A manometric study. AB - The objective of this study was to investigate the effects of the opioid loperamide and its recently synthesized pharmacologically inactive prodrug loperamide oxide on the anal sphincter. In a double-blind, placebo-controlled crossover study, anorectal manometry was performed in 12 healthy volunteers five hours after oral bolus application of 10 mg of loperamide, loperamide oxide, or placebo. Loperamide significantly increased the threshold volumes for minimal perception and urgency to defecate (P less than 0.05) and raised the volume required to abolish recovery of the rectoanal inhibitory reflex (P less than 0.05). These findings suggest that loperamide has a specific continence-improving action on the anal sphincter. However, anal resting pressure and maximal squeeze pressure were unaffected in our study and do not seem to be responsible for this effect. The effects under loperamide oxide showed a similar tendency but were without statistical significance. PMID- 1511647 TI - Direct comparison between Czerny-Lembert and circular-stapled anastomotic techniques in colorectal anastomosis: a similar pattern of healing for both. AB - There are scant experimental data directly comparing the healing of the circular stapled (CS) anastomotic technique with the standard Czerny-Lembert two-layer hand-sewn (HS) anastomotic technique during the acute and chronic phases of healing. The purpose of this study, therefore, was to serially evaluate wound healing in CS and HS anastomoses in the normal porcine colorectum. Forty-two adult female mixed-breed pigs randomly underwent either HS or CS anastomosis at the sacral promontory. Laser Doppler velocimetry (LDV), was used to measure perianastomotic blood flow. Groups of animals underwent a second surgery at 3, 5, 11, 60, or 120 days postoperatively, and anastomoses were restudied using LDV, gross and microscopic grading of inflammation, bursting pressures, and hydroxyproline content. Additionally, the 60-day and 120-day groups of animals underwent preoperative biplanar barium enemas to identify leaks or stenoses. No significant differences in perianastomotic blood flow between the HS and CS techniques were obtained over the entire 120-day study period. Serial evaluation of wound healing revealed no significant differences between the two anastomotic techniques with respect to bursting pressures, gross or microscopic inflammatory scores, or hydroxyproline content. There were no leaks or stenoses with either technique. Despite earlier reports to the contrary, there appears to be no fundamental difference in the mode of healing in the porcine colorectum comparing the HS technique with the CS technique. PMID- 1511648 TI - Consequences of delayed ileostomy closure after ileal pouch-anal anastomosis. AB - Temporary diverting loop ileostomy is a generally accepted component of the ileal pouch-anal anastomosis (IPAA) procedure. Ileostomy closure is usually performed within two to three months but may be delayed because of disruption of the ileonanal anastomosis, suspected leak from the ileal reservoir, concomitant medical problems, or patient convenience. Of 362 patients undergoing IPAA at The Cleveland Clinic Foundation for inflammatory bowel disease, 10 have had their ileostomy closures delayed for more than six months. Clinical and manometric parameters are examined in these patients and compared with those who had earlier closure. There appears to be no significant difference in the functional outcome of IPAA in these patients in terms of number of bowel movements and degree of continence. Reservoir compliance and maximum tolerated volumes are similar. We conclude that delaying ileostomy closure for more than six months after IPAA has no deleterious effect on pouch function. PMID- 1511649 TI - Rectoanal inhibitory reflex following low stapled anterior resection of the rectum. AB - The rectoanal inhibitory reflex plays an important role in the normal mechanisms of anorectal continence. Anterior resection abolishes the reflex, but whether it recovers, particularly after inverted stapled anastomosis, is not clear. Anal manometry was performed on patients undergoing low anterior resection for carcinoma. Maximum anal resting pressure and the rectoanal inhibitory reflex were assessed preoperatively and up to two years postoperatively. The reflex was present in 43 of 46 patients (93 percent) preoperatively, in 8 of 45 patients (18 percent) on the 10th postoperative day, and in 6 of 29 patients (21 percent) between six months and one year following surgery. Twenty patients were studied more than two years postoperatively, and in 17 (85 percent) the reflex was demonstrated. In the majority of low anterior resection patients, the rectoanal inhibitory reflex is abolished by surgery, remains absent throughout the first year, and has recovered by the end of the second postoperative year. This may be important in the recovery of anorectal function in these patients. PMID- 1511650 TI - Proliferative activity of colonic mucosa at different distances from primary adenocarcinoma as determined by the presence of statin: a nonproliferation specific nuclear protein. AB - The field change is one hypothesis concerning the development of colorectal carcinoma. Removal of a carcinoma without its entire surrounding altered mucosa may result in the development of a recurrence. S44, a monoclonal antibody directed against statin, a nuclear protein expressed in nonproliferating cells in either a quiescent or senescent state, was used to determine the rate of cell growth in colorectal mucosa at different distances from carcinomas. The specimens of 18 patients undergoing resection of a colorectal carcinoma were immediately opened after operation, and strips of mucosa were taken at distances of 1 cm, 5 cm, and 10 cm from the carcinoma. For each location, 10 longitudinally oriented crypts were evaluated for statin-positive cells identified by the presence of a dark brown peroxidase-conjugated antibody reaction product. The average percentage of statin-positive cells per crypt was significantly lower at a 1-cm distance from the carcinoma compared with the mucosa located 5 and 10 cm from the carcinoma (20.89 +/- 4.33 at 1 cm, 32.41 +/- 5.27 at 5 cm, and 34.23 +/- 6.45 at 10 cm). None of the calculated parameters showed any significant difference between the 5-cm and 10-cm locations. The fact that the proliferation rate of the mucosal cells returns to the normal level at 5 cm from the margin of the carcinoma suggests that cells located within this distance still retain proliferative potential even though they are morphologically indistinguishable from their normal counterparts. We conclude that failure to remove this transitional, potentially proliferative mucosa may result in subsequent development of anastomotic or perianastomotic recurrences. PMID- 1511651 TI - Healing of ischemic colonic anastomosis: fibrin sealant does not improve wound healing. AB - Fibrin adhesives have been advocated as a protective sealant in high-risk colonic anastomoses to prevent leakage. To assess the effect of fibrin glue sealing on the healing ischemic anastomosis, we compared the healing of sutured colonic anastomoses in the rat, with and without fibrin adhesive (Groups IA and IB), and ischemic anastomoses with and without fibrin adhesive (Groups IIA and IIB). On days two, four, and seven, 10 animals in each group were sacrificed. Adhesion formation was scored, and the in situ bursting pressure was measured. The collagen concentration and degradation were estimated by measuring hydroxyproline. Adhesion formation was more prominent in Groups IB, IIA, and IIB on day four only; abscesses were noted in the ischemic group in four rats. Anastomotic bursting pressure was significantly lower in sealed (IB) and ischemic anastomoses (IIA) than in normal anastomoses (IA) on day four. Sealing of ischemic anastomoses did not change bursting pressures on days two, four, and seven. The relative decrease of collagen in the sealed anastomoses is significantly higher on day four only. It is concluded that sealing of normal colonic anastomoses in the rat has a negative effect on wound healing. Ischemia at the anastomotic site results in weaker anastomotic strength on day four postoperatively. Also in ischemic anastomoses, fibrin sealant does not improve wound healing during the first seven days. Adhesion formation on ischemic intestinal anastomoses was not prevented by fibrin sealing. PMID- 1511652 TI - Are intersecting staple lines a hazard in intestinal anastomosis? AB - To determine the safety of intersecting staple lines, 22 pigs were operated upon with a functional end-to-end enteroanastomosis 40 cm distal to the ligament of Treitz using linear stapling devices. The procedure was repeated on the colon, where a colocolostomy was created. The blood flow at intersecting staple lines and single-row staple lines for each anastomosis was studied with the reference organ method 24 hours after the first operation. The purpose was to evaluate whether there is a reduction in blood flow at the site of intersecting staple lines, causing an increased risk for anastomotic leakage. The reduction in mean blood flow in crossing compared with noncrossing staple lines was 6 percent (-5 17 percent) for small bowel anastomoses and 7 percent (-6-19 percent) for colonic anastomoses. An equivalence test showed that, if a reduction in blood flow exists between crossing and noncrossing staple lines, it is most likely less than 30 percent (P less than 0.001) for both small bowel and colonic anastomoses. This experimental study demonstrates that intersecting staple lines in small bowel and colonic anastomoses do not reduce anastomotic blood flow to a dangerous level. PMID- 1511653 TI - Experimental carcinogenesis at sutured and sutureless colonic anastomoses. AB - This study explores the role of sutures and the healing colonic wound in experimental carcinogenesis. One hundred sixty rats underwent surgery with colotomy and repair using silk, steel, or Vicryl (Ethicon, Somerville, NJ) sutures or a sutureless technique. Forty rats had a sham procedure. All animals received azoxymethane for 12 weeks at a dose of 10 mg/kg/week. Half the rats commenced carcinogen before surgery, and half commenced it eight weeks after surgery. Animals with anastomotic tumors were found in 46 percent of the sham group (P less than 0.05 cf. sutured), 41 percent of the sutureless group (P less than 0.02 cf. sutured), and 68 percent of the sutured group. The corresponding figures for anastomotic carcinoma were 9 percent (P less than 0.001 cf. sutured), 22 percent, and 38 percent. No significant differences in tumor yield were noted among the different sutures. However, several differences were noted between the two carcinogen models. In those animals that received surgery first, there was a higher incidence of anastomotic tumors (P less than 0.002) and cancers (P less than 0.0001) in the sutured and sutureless groups, and those tumors that occurred in the sutured group were considerably larger than in those that had carcinogen first (15.9 mm cf. 4.9 mm; P less than 0.0001). Overall, all sutures seem to enhance anastomotic tumor formation, and we would suggest that a sutureless anastomosis may diminish this risk. PMID- 1511654 TI - Use of laparoscopic vascular stapler at laparotomy for colorectal cancer. PMID- 1511655 TI - Rectosigmoid stent for obstructing colonic neoplasms. AB - Attempting proctoscopic placement of a rectosigmoid stent is proposed as a first step in treating obstructing rectosigmoid neoplasms. If stent placement is successful, elective colon resection can be performed following treatment of any coexisting medical problems that would complicate an emergency colon resection and after routine mechanical bowel preparation. PMID- 1511656 TI - The diabetic foot problem--a failed system of health care? AB - It is evident that there is excess morbidity and mortality as a consequence of foot problems in patients with diabetes mellitus. Most of the data relative to foot lesions is taken from the study of subsets of diabetic patients undergoing lower extremity amputation. Such data probably do not provide accurate information relative to the incidence and/or prevalence of diabetic foot problems. Available evidence does suggest that diabetic foot care may be inadequate and the efficacy of various diagnostic and therapeutic modalities has not been proven. Advances have been made in obtaining a better understanding of the microbiology of lower extremity infected lesions both in hospitalized patients and in those subjects being followed in the outpatient setting. Attention should be directed at developing a systematic classification of foot lesions which can be universally applied. We need to understand and relate to those risk factors contributing to the development and progression of lower extremity lesions in the diabetic patient. In evaluating the efficacy of diverse diagnostic and therapeutic approaches, well-controlled clinical investigations need to be undertaken. Attention should be focussed upon both measures of process and outcome where appropriate. Finally, there needs to be recognition that the problem of the diabetic foot lesion represents a major public health challenge. PMID- 1511657 TI - First phase insulin release in the non-obese diabetic mouse: correlation with insulitis, beta cell number and autoantibodies. AB - The ontogenic variation of beta cell function and its relationship with the degree of islet damage and levels of autoantibodies have been studied in the non obese diabetic (NOD) mouse model. We conducted in vivo first phase insulin release (FPIR) in response to intravenous glucose and studied its correlation with the degree of insulitis, islet cell antibody (ICA) and insulin autoantibody (IAA) levels in female NOD mice cross-sectionally at days 40 (n = 19), 90 (n = 21), 150-160 (n = 21) and day 250 (n = 20). The mean +/- SEM FPIR values showed an age-related decline from day 40 (46.2 +/- 5.3 microU/ml) to day 150-160 (17.8 +/- 2.5 microU/ml) and then doubled at day 250 (34.5 +/- 5 microU/ml), while the mean +/- SEM insulitis scores increased progressively until day 150-160 (61.7 +/- 6.1%) and then declined slightly at day 250 to 50.2 +/- 6.2%. In female NOD mice with spontaneous diabetes (n = 4) and streptozotocin-induced diabetic Swiss mice (n = 5) FPIR was either absent or greatly attenuated. A statistically significant inverse correlation between FPIR and insulitis was found among NOD mice at days 90 (P = 0.02; r = -0.52) and 150-160 (P = 0.03; r = -0.48). However, no statistically significant correlation was observed at days 40 and 250. Morphometric techniques applied to day 150-160 pancreatic sections showed a statistically significant negative correlation between insulitis and beta cell number per unit area of islet tissue (P = 0.0001; r = - 0.75). At this age some islet beta cells showed different intensities of staining by immunofluorescence.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1511658 TI - Periodicity of insulin secretion comprises multiple cycles with different duration in perfused rat islets. AB - Insulin secretion from pancreatic islets has been found to be periodic by in vivo and in vitro experiments. The pacemaker which regulates the periodicity may be localized in the central nervous system or in the pancreas, though the precise location and the mechanisms of generating pacing have not been determined. In order to solve these problems, we examined the period of secretory cycles of insulin in isolated islets using a prolonged perfusion system, and investigated the effects of glucose and other agents on these periods. Isolated islets from male Wistar rats were enclosed in a millipore holder and were perfused with MEM containing 1 mg/ml glucose at a flow rate of 0.3 ml/min for 240 min. The effluent was collected at 1-min intervals to measure insulin secretion. The results were analyzed by the maximum entropy method to demonstrate the periodicity of insulin secretion. When islets were perfused with 1 mg/ml glucose, the periodicity comprised five cycles with different duration: 71.5 +/- 14.6 min, 29.8 +/- 3.4 min, 19.2 +/- 1.5 min, 11.6 +/- 2.1 min and 4.3 +/- 0.4 min. This indicates the presence of a pacemaker within the islets, although, in vivo, participation of a higher center to control periodicity has to be taken into account. Further, the presence of a long cycle (71.5 +/- 14.6 min) of insulin secretion which previously has only been observed in vivo was first demonstrated in this in vitro study. The cycles were consistent even in islets which were desensitized to glucose by cultivating in a high glucose medium for 5 days before perfusion.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1511659 TI - Lack of specificity of islet cell surface antibodies (ICSA) in IDDM. AB - Human islets were isolated by collagenase digestion and tissue culture from pancreata obtained from organ donor subjects and dispersed islet cells were prepared from hand-picked islets. Islet cell surface antibodies (ICSA), detected by indirect immunofluorescence on isolated islet cells, were present in sera from nine of 22 (41%) subjects with recent-onset insulin-dependent diabetes mellitus (IDDM) and three of 11 (27%) control subjects. Sera had been heat inactivated, adsorbed against a human B lymphoblastoid cell line (IM-9) and tested in the presence of 4% bovine serum albumin. However, with a double labelling technique, we were unable to show that ICSA were specific for beta cells. Of the nine ICSA positive IDDM sera, three stained both beta and non-beta cells, three beta cells only and three non-beta cells only; the three ICSA-positive control sera stained both beta and non-beta cells. There was no apparent relationship between ICSA and standardised measurements of islet cell antibodies (ICA) and insulin autoantibodies (IAA). These results lead us to question whether, despite previous reports, ICSA are specific for beta cells or indeed for IDDM. PMID- 1511660 TI - Nasal glucagon in the treatment of hypoglycaemia in type 1 (insulin-dependent) diabetic patients. AB - The aim of this study was to compare the effect of nasally administered glucagon in doses of 1 (A) and 2 mg (B), with 1 mg glucagon administered intramuscularly (C) in 12 C-peptide-negative IDDM patients. Spontaneous recovery (D) from insulin induced hypoglycaemia in the same patients was used as reference. The mean age was 31.1 (21-48) years, diabetes duration 10.8 (2.7-31) years and HbA1c 7.7 (6.5 9.8)%. Hypoglycaemia was induced by i.v. insulin infusion. When blood glucose (BG) reached about 2 mmol/l either glucagon was administered or the patients recovered spontaneously. BG nadir was 1.6 (1.1-2.3) mmol/l. BG increments during the first 15 min after glucagon administration were: (A) 1.9 +/- 0.7 (0.4-3.0); (B) 2.5 +/- 0.7 (1.5-3.5); (C) 2.5 +/- 1.0 (1.2-4.7); and (D) 0.3 +/- 0.4 (0-1.0) mmol/l, respectively. All treatments were more effective, measured as increments in BG, than spontaneous recovery, P less than 0.00001. There was no difference between nasal treatment with 2 mg (B) and i.m. treatment (C), both being more effective than 1 mg (A) nasal treatment, P less than 0.1. BG continued to increase up to 10 mmol/l 90 min after i.m. glucagon administration, whereas it stabilized at a level of 4.6-6 mmol/l, 30-45 min after nasal administration. Eighty percent of the patients had side-effects to nasal administration - local irritation, rhinitis or sneezing. Half of the patients sneezed, without correlation with the delivered dose of glucagon. None of the patients had side effects which would preclude further treatment.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1511661 TI - Reliability of glucose measurement by glucose test strips in tropical conditions. AB - The reliability of glucose test strips and reflectance meters after storage in tropical conditions was assessed. In a first experiment, sealed bottles containing glucose test strips were stored for 1 month in closed sterilising ovens at 40 degrees C, one in dry (0% humidity) and the other in wet (75% humidity) conditions. Results were compared to measurements obtained with glucose test strips stored under standard Western conditions, in non-diabetic and diabetic patients, using the same standard reflectance meter. A second experiment was performed similarly, comparing the values obtained with reflectance meters stored in different conditions, using standard glucose test strips. Reproducibility was assessed on the basis of duplicate measurements for each condition of storage. We observed that temperature and humidity did not significantly affect the glucose test strips (1st experiment), while a slight underestimation of capillary blood glucose was found using reflectance meters stored at 50 degrees C, irrespective of the humidity (2nd experiment). All the correlation coefficients between duplicates were greater than 0.975 irrespective of the conditions of storage for glucose test strips and reflectance meters. Therefore, glucose test strips and reflectance meters appear fairly reliable at the grass-root level in the tropics, if used carefully. PMID- 1511662 TI - Urinary albumin excretion rate (AER) in newly-diagnosed type 2 Indian diabetic patients is associated with central obesity and hyperglycaemia. AB - Urinary albumin excretion rate (AER) was measured in non-diabetic controls (n = 143) and newly diagnosed impaired glucose tolerant (IGT, n = 64) and non-insulin dependent (type 2) diabetic patients (n = 146). AER progressively increased from non-diabetic [3.7 (1.1-51.3) micrograms/min, median (5-95th centile)] to IGT [4.8 (1.3-53.7)] and diabetic [7.3 (1.4-91.6)] groups. Eight percent of non-diabetic, 19% of IGT and 23% of type 2 diabetic patients showed 'microalbuminuria' (AER, 20 200 micrograms/min) (non-diabetic vs diabetic P less than 0.01, non-diabetic vs IGT NS, IGT vs diabetic NS). AER was directly related to waist-hip ratio (P less than 0.001) and HbA1 (P less than 0.01) in diabetic patients; 80% of diabetic patients with microalbuminuria were men (P less than 0.06 compared to 'normoalbuminuric' diabetic patients). Association of AER with waist-hip ratio was present in men as well as women. Thus, in the newly diagnosed type 2 Indian diabetic patients AER is associated with central obesity in addition to its well known association with hyperglycaemia. Our findings offer a possible explanation for the increased risk of proteinuria in diabetic men than in women because men are centrally more obese. It could also explain previous reports of higher AER in migrant Asian diabetic patients in the U.K. compared to native white Caucasian diabetic patients because Asians are known to be more centrally obese. PMID- 1511663 TI - Hypertension in newly diagnosed non-insulin-dependent diabetic subjects. AB - Medical records of newly diagnosed non-insulin-dependent diabetic patients attending a Diabetic Centre in Modena, northern Italy, during the period 1985-88 were reviewed to analyze the prevalence of hypertension at age of diagnosis of diabetes and its association with selected risk factors. The prevalence of hypertension was also determined in a representative sample of control subjects. In the multivariate analysis, greater body mass index and older age, but not smoking, were strongly associated with increased rates of hypertension both in control and in diabetic subjects. In diabetic patients, family history of diabetes, defined as presence of diabetes in close relatives, was not significantly associated with hypertension, while rates of hypertension were significantly lower in patients who reported at least one parent affected by diabetes. After adjustment for age and body mass index, newly diagnosed non insulin-dependent diabetes was not an independent risk factor for hypertension. These findings seem to be consistent with the hypothesis that diabetes and hypertension are not linked by a common genetic background. PMID- 1511664 TI - Physiologic concentrations of inorganic phosphate accelerate fructosamine synthesis. AB - The effect of physiologic concentrations of inorganic phosphate (Pi) on fructosamine (FRA) synthesis was studied. After 75 g oral glucose administration (OGTT), 'delta FRA/24 h', defined as delta FRA after incubating serum or other specimens at 37 degrees C for 24 h after adding 1000 mg/dl glucose, was significantly decreased in parallel to the decrease of plasma Pi concentrations. 'The FRA index', defined as the FRA value divided by the corresponding glucose concentration, both at fasting, correlated significantly with plasma Pi concentrations. In vitro incubation of serum total protein (TP), albumin (ALB), gamma-globulin (GLB), free lysine (Lys), and free valine (Val) with glucose at different concentrations of Pi showed a Pi-dependent increase of FRA synthesis throughout 48 h of incubation. The accelerating effect of 5 mg/dl Pi on FRA synthesis from TP, ALB, GLB, Lys, and Val at pH 7.4 was, respectively, as great as 48, 20, 24, 13 or 25% of those without Pi. Increase of pH from 6 to 10 logarithmically increased delta FRA/24 h in contrast to a logarithmic decrease of the accelerating effect of Pi on delta FRA/24 h. These data show that physiologic concentrations of Pi accelerate protein glycation by accelerating dehydrogenation during the Amadori rearrangement through the negative charge of Pi. Because this accelerating effect of physiologic Pi presumably exists in vivo, Pi concentration must be taken into account as an accelerating factor for FRA synthesis in evaluating diabetic control, and further studies must be carried out to elucidate whether hyperphosphatemia accelerates glycation-induced diabetic complications. PMID- 1511665 TI - [Molecular-genetic analysis of radiation-induced mutation of the white gene, inserted in the 45D region of the second Drosophila melanogaster chromosome]. PMID- 1511666 TI - [Effect of dihydroriboflavin esters on the lipid peroxidation process in rat liver microsomes]. PMID- 1511667 TI - [The mechanism of superoxide dismutase inactivation by stimulated neutrophils]. PMID- 1511668 TI - Current needs for increased accuracy and precision in measurements of low levels of lead in blood. AB - Needs for accurate and precise measurements of low levels of lead in blood are discussed. Current methodologies are sufficient for measuring blood lead (PbB) levels greater than 0.5 microM, but the accuracy and precision of those methodologies are inadequate for measuring lower (less than 0.5 microM) PbB concentrations. These analytical limitations are primarily due to contamination bias incurred during sample collection, processing, and analyses. Consequently, trace metal-clean procedures should be adopted to elucidate the contribution of environmental lead to the PbB levels of the U.S. population and to estimate the threshold(s) of subclinical lead toxicity. PMID- 1511669 TI - Neurobehavioral effects of formaldehyde and solvents on histology technicians: repeated testing across time. AB - Neurobehavioral functions were studied by periodic testing of 318 histology technicians and by a single session testing 494 of such technicians from 1982 through 1986. Tests included immediate recall of stories, of drawings, and of number series from the Wechsler Memory Scale, block designs from the Wechsler Adult Intelligence Scale (WAIS), slotted pegboard, trail making A and B, embedded figures, number writing on the fingers, visual simple and two-choice reaction times, balance (speed of body sway), and the profile of mood state (POMS) score. Mean test scores of four initial "first test" groups were not different from 1982 to 1986. Immediate recall of stories and drawings improved on the first retest as did the block design score. Other test scores showed insignificant variation over the 4 years, including memory for numbers forward and backward, trails A and B, number writing on fingers, radius of body sway, and choice reaction time. Only placing of pegs in the pegboard took longer. POMS score was lower in the second year in naive subjects and decreased from 39 to 13 in those retested. Variations in results of neurobehavioral tests given at intervals across 4 years were small. No cumulative effects of occupational exposures or of aging were found. However, small decreases may have been offset by increases due to test familiarity or learning. PMID- 1511670 TI - Residential exposure to chromium waste--urine biological monitoring in conjunction with environmental exposure monitoring. AB - To determine whether a population living on or adjacent to four sites of chromate production waste was measurably exposed to environmental chromium, spot samples of urine were collected along with wipe samples of household dust and lifestyle/activity interview data. Findings were compared to those from a control population in two communities with no significant chromium use or waste sites. Urine samples were collected and analyzed, employing measures to minimize background chromium contamination. The average Cr mass in dust was 3.7 times that in control houses. The mean creatinine-corrected urine Cr (Cr/c) level of the exposed subgroup residing in households in the 75th percentile of Cr mass in wipe samples was significantly greater than that of the control population. This subgroup was primarily located at a single exposure location. Using lifestyle/activity data, significantly elevated Cr/c urine levels were identified in other exposed subgroups defined by employment location and by outside play time. These data show an association between elevated exposure to chromium in household dust and elevated urine levels of chromium, consistent with residential exposure to chromate production waste. These data also suggest an association between chromium exposure and activities outside the home which are consistent with exposure to chromate production waste. PMID- 1511671 TI - Asbestos in organs and placenta of five stillborn infants suggests transplacental transfer. AB - Digests of lungs, liver, and placenta from five stillborn infants of 22 to 38 weeks gestational age were examined for asbestos and other fibers using light and electron microscopy, energy dispersive X-ray analysis, and selected area diffraction analysis. Uncoated chrysotile asbestos fibers were found in the digests of at least one of the three tissues examined from each stillborn infant. The asbestos fiber burdens ranged from 71,000 to 357,000 fibers/g wet tissue. Most of the fibers were small, with the mean length ranging from 0.83 to 2.53 microns. While appreciable numbers of uncoated chrysotile fibers were present, no coated asbestos fibers were found in any of the stillborns. Both coated and uncoated nonasbestos fibers were found in at least one of the tissue digests of all five stillborns. The uncoated nonasbestos fibers were characterized as aluminum silicates, diatomaceous earth fragments, or other fibers. The coated nonasbestos fibers or ferruginous bodies were consistent with being formed on diatomaceous earth fragments, black carbon cores, or sheet silicate cores. Since the placenta is the only route of communication between the fetus and the outside environment, our findings strongly suggest a transplacental transfer of asbestos and other fibers in humans. PMID- 1511672 TI - The effect of ozone associated with summertime photochemical smog on the frequency of asthma visits to hospital emergency departments. AB - A retrospective study using ambient ozone, temperature, and other environmental variables and their effect on the frequency of hospital visits for asthma was conducted in New Jersey, an area that often exceeds the allowable national standard for ozone. Data on emergency department visits for asthma, bronchitis, and finger wounds (a nonrespiratory control) were analyzed for the period May through August for 1988 and 1989. Asthma visits were correlated with temperature while the correlation between asthma visits and ozone concentration was nonsignificant. However, when temperature was controlled for in a multiple regression analysis, a highly significant relationship between asthma visits and ozone concentration was identified. Between 13 and 15% of the variability of the asthma visits was explained in the regression model by temperature and ambient ozone levels. This association, when compared to similar studies in Canada, shows the contribution of ozone to asthma admissions to be stronger in areas with higher ozone concentrations. Thus, among regions with periodic accumulations of ozone in the ambient atmosphere, an exposure-response relationship may be discernible. This supports the need to attain air quality standards for ozone to protect individuals in the general population from the adverse health effects caused by ambient ozone exposure. PMID- 1511673 TI - Sugarcane exposure and the risk of lung cancer and mesothelioma. AB - A case-control study was conducted of the risk of lung cancer and mesothelioma from environmental and occupational exposures associated with sugarcane production. A slight, not statistically significant, excess risk of lung cancer was observed among participants who reported working in the sugarcane industry (odds ratio 1.8, 95% confidence interval 0.5-7.5). No increased risk was observed among our population, associated with living near sugarcane growing areas. Little difference was observed between cases and controls in years employed in the industry or jobs performed. Only one mesothelioma case and no controls reported working in the sugarcane industry. PMID- 1511674 TI - Elementary school absences and PM10 pollution in Utah Valley. AB - This study assessed the association between school absenteeism and respirable particulate pollution (PM10) in Utah Valley for the six school years of 1985 to 1990. Weekly absenteeism data from the Provo School District and daily data from a single elementary school in the Alpine School District were analyzed for kindergarten through sixth grade. PM10 concentrations during the study period averaged approximately 50 micrograms/m3 with the 24-hr maximum equal to 365 micrograms/m3. Absenteeism was regressed on PM10 pollution levels, temperature, snowfall, and variables indicating day of week, month of school year, and days preceding and following holidays and extended weekends. Estimated associations between absenteeism and PM10 pollution in both data sets were positive, statistically significant (P less than 0.01), and robust to different model specifications. PM10 effects persisted for up to 3 or 4 weeks. Regression results from both data sets indicated that an increase in 28-day moving average PM10 equal to 100 micrograms/m3 was associated with an increase in the absence rate equal to approximately two percentage points, or an increase in overall absences equal to approximately 40%. Similar relationships were observed for all grade levels, although the response of absences to air pollution was generally greater for grades 1-3 compared with grades 4-6. Associations between absenteeism and PM10 pollution were observed even for levels below 150 micrograms/m3. PMID- 1511675 TI - Experimental studies on the pathogenesis of the gastric mucosal lesions induced by whole-body vibration. AB - In order to determine the pathogenesis of gastric mucosal lesions induced by whole-body vibration (WBV), the effects of WBV (3.0 G, 10 Hz, 90 min) on gastric mucosal blood flow (GMBF), plasma corticosterone (COR) and catecholamines (CA), and gastric ulcer formation were investigated in relation to the effects of forced water-immersion stress (FWI) upon the same parameters. While WBV increased GMBF during the exposure, FWI decreased it both during and after the stress. No difference in the severity of ulcer formation between the WBV and the FWI groups was seen. Both WBV and FWI increased plasma COR and CA, although the degree of the increase in COR that accompanied WBV was less than that associated with FWI. Truncal vagotomy attenuated the reduction of GMBF and the extent of ulcer formation that occurred with FWI, but promoted a reduction of GMBF with WBV. These findings indicate that ulceration induced by WBV may be caused primarily by its direct and specific mechanical actions and not by indirect, central nervous system effects known to be important in the pathogenesis of ulcerations produced by mental stress. PMID- 1511676 TI - Styrene in adipose tissue of nonoccupationally exposed persons. AB - Given a styrene tissue/blood partition coefficient of ca. 39 and a relatively low perfusion rate of ca. 0.03 ml/min-g tissue, adipose tissue provides a useful physiologically damped integrative measure of environmental exposure. Styrene in the adipose tissue of nonoccupationally exposed individuals was measured for the first time. Tissue samples obtained from elective surgery patients and postmortem donors were analyzed by capillary gas chromatography and found to contain 1.12 +/ 1.06 (mean +/- SD) ppm styrene. Using these measured tissue levels and an apparent clearance of styrene (defined as the ratio of blood clearance to adipose tissue/blood partition coefficient), environmental intake of styrene was estimated to be 2.23 mg/hr, corresponding to an inhaled concentration of 1.96 mg/m3 (476 ppb). This value is two to three orders of magnitude higher than typical breathing zone air measurements, indicating additional undiscovered sources of styrene exposure. PMID- 1511677 TI - Postnatal lead exposure affects motor skills and exploratory behavior in rats. AB - The present study was undertaken to investigate the behavioral effects of postnatal lead exposure. Newborn male Sprague-Dawley rats were given 1 or 8 mg/kg lead acetate intraperitoneally daily for 20 days. Control rats received 1 mg/kg sodium acetate, or 8 mg/kg sodium acetate in oversized litters. The high dose lead acetate group and the high dose, oversized sodium acetate group showed impaired weight and length increment during the end of the treatment. Rats treated with the higher dose of lead showed delayed eye opening. The time required to turn in a negative geotaxis test was transiently longer in rats treated with the higher dose of lead. A tendency of reduced forepaw grasping ability was seen in lead-treated rats during the end of the lead exposure. Ambulation and rearing in an open field were lower for the rats treated with the higher dose of lead acetate during certain periods of development. Impaired performance in a balancing rod test was also seen in the rats treated with the higher dose of lead at the adult stage, while no difference was seen in ambulation or gnawing activity during tail pinch-induced stress. Thus, lead intoxication in rats during the early postnatal period, with doses that approximate those in children, induced transient as well as persistent dysfunctions in exploratory behavior and motor skills. These observed actions of lead may be related to impaired maturation of sensitive brain regions which develop postnatally. PMID- 1511678 TI - A method for the generation of monoclonal antibodies against rare cell-surface molecules. AB - Monoclonal antibodies provide a powerful tool for the identification and analysis of novel cell-surface molecules. We present here a method for antigen preparation and an immunization protocol that facilitates generation of mAb reactive with cell-surface molecules of low abundance and/or low antigenicity. The procedure involves isolation and extensive fractionation of cell-surface and detergent soluble extracellular-matrix molecules prior to immunization. Cell-surface proteins on intact tissue are biotin-labeled using a reagent that does not penetrate cells. Avidin affinity chromatography is then used to purify these biotinylated molecules. Size-exclusion HPLC is used to separate these surface molecules on the basis of apparent molecular mass. Finally, immunization with antigen coupled to keyhole-limpet hemocyanin is combined with long-term booster immunizations to generate a hyperimmune response resulting in high-affinity IgG. A test application of this approach was aimed at the generation of mAb against cell-surface molecules of approximately 135 kDa in the developing chicken retinotectal system. Immunochemical analyses using antibodies produced by this approach which showed restricted patterns of tissue staining reveal that mAb were generated against all previously identified immunoglobulin superfamily molecules of this size in this system. Furthermore, we produced many additional antibodies that labeled retinotectal tissue in novel staining patterns. In the two cases analyzed in detail, these new patterns reflect the distributions of previously uncharacterized members of the immunoglobulin superfamily. The success of this initial study suggests that this method may represent a broadly applicable approach towards the preparation of extensive libraries of antibodies against cell-surface molecules expressed on cells from numerous sources. PMID- 1511679 TI - Molecular dynamics study of a complex between the human histocompatibility antigen HLA-A2 and the IMP58-66 nonapeptide from influenza virus matrix protein. AB - The structure of the influenza-virus-matrix-protein (IMP) 58-66 nonapeptide, bound to the major-histocompatibility-complex-encoded human leukocyte antigen (HLA) A2 protein was studied by molecular dynamics simulation. Starting from the extra electron density map of peptides co-crystallized with HLA-A2, the nonapeptide IMP58-66 was docked residue by residue in the protein binding cleft. The complex was simulated for 100 ps in a shell of 1372 water molecules. The averaged simulated HLA-A2 conformation was found to be similar to the crystal structure (0.182 nm RMS deviation, for the backbone atoms of the alpha 1-alpha 2 domain). Nine out of the 14 hydrogen bonds observed in the antigen-binding site were reproduced in the simulation. The IMP58-66 peptide exhibits an extended conformation with kinks at positions 3 and 5. The side chains of residues 2, 3 and 9 develop van der Waals' interactions with hydrophobic pockets of HLA-A2, corresponding to polymorphic residues of the major-histocompatibility-complex encoded proteins. Both the N-terminus and C-terminus of the nonapeptide were anchored in the antigen-binding groove by hydrogen bonds with conserved amino acids. The N-terminus was more flexible and contacts four HLA-A2 conserved tyrosines (Tyr7, Tyr59, Tyr159 and Tyr171) and Glu63 by direct or water-relayed hydrogen bonds. Water intercalation occurred only around the N-terminus of the peptide, the C-terminal carboxylate forming strong hydrogen bonds with polar residues (Tyr84 and Thr143) and a salt bridge with Lys146 all over the molecular dynamics simulation. This model is fully compatible with the recently published crystal structure of the HLA-B27 protein, complexed by a mixture of self nonapeptides. PMID- 1511680 TI - A study of the hinge-bending mechanism of yeast 3-phosphoglycerate kinase. AB - The hinge-bending mechanism proposed as part of the catalytic mechanism for phosphoglycerate kinase (PGK) has been investigated using yeast PGK and the site directed mutant [H388Q]PGK, where His388 is replaced by Gln. The emission and quenching of fluorescence, supported by the aromatic CD band, show that the mutation in the waist region affects the tryptophan environment in the C-terminal domain. The mutant is also less stable to guanidine denaturation and less cooperative in its unfolding. The effect of substrates on the conformation of PGK was studied using 8-anilino-1-naphthalenesulphonic acid (ANS), a competitive inhibitor of ATP binding to the C-terminal domain, and 8-(2 [(iodoacetyl)ethyl]amino)naphthalene (I-AEDANS), attached to Cys197 on the N terminal domain. Under the influence of substrates the novel anisotropy decay curves for ANS indicate a 1-5 degrees change in the orientation of the probe, interpreted as a small reorientation of the domains about the waist region. The experimental data are interpreted as a small swivelling of the domains about the waist region under the influence of substrate. The results with AEDANS anisotropy decay are consistent with those for ANS. The enzyme activity of PGK shows a break in the Arrhenius plot at 20 degrees C mirrored by a break in the temperature dependence of tryptophan ellipticity. This is interpreted as a change in protein dynamics associated with destabilisation of the waist region. This destabilisation is shown to have already taken place in the mutant enzyme and in the wild type at pH 5.6, both of which exhibit linear Arrhenius plots. NMR titration curves show that the pH effect must be due to a group other than histidine. The results give further support to the permissive model of hinge bending previously proposed by one of the authors, in which binding of substrate destabilises the waist region. This loosens the hinge which can then swing slightly to bring the domains closer together to make favourable interactions between the domains and the substrates, with the exclusion of water. PMID- 1511682 TI - Thermodynamics of cation binding to Nereis sarcoplasmic calcium-binding protein. Direct binding studies, microcalorimetry and conformational changes. AB - Nereis sarcoplasmic calcium-binding protein contains three functional EF-hand sites which bind Ca2+ or Mg2+ competitively. Here it was confirmed over a large range of [Mg2+] that the positive cooperativity in binding of Ca2+ (nH = 2) is the result of allostery in Mg2+ dissociation. At pH 7.5, Ca2+ or Mg2+ binding provokes the release of 1.4 mol proton/mol protein, whereas no protons are released during Ca(2+)-Mg2+ exchange. The enthalpy change as a function of Ca2+ binding yields a two-step curve with an inflection point at 1 mol Ca2+/mol protein and a maximum of -66 kJ/mol at 3 mol Ca2+/mol protein. Binding of three Mg2+ ions is cooperative (nH = 1.8) with a maximal enthalpy change of -15.1 kJ/mol protein. Difference spectroscopy led to the conclusion that, in the metal free protein, the structure around the aromatic residues is well organized, but that Tyr and Trp residues are still solvent-exposed. Upon Ca2+ binding Tyr and Trp spectra are blue-shifted, but some Trp residues are confined to a positively charged pocket. Examination of the Ca(2+)-saturated three-dimensional crystal structure confirmed that Trp4 and Trp57 are located in such pockets or clefts, close to the surface. During the allosteric T----R transition, promoted by binding of the first Mg2+, the Trp residues move to a hydrophobic environment. For both Ca2+ and Mg2+, the enthalpy change and the conformational change in the environment of the aromatic residues is much more pronounced in the first, than in the subsequent two binding steps. In this respect, the latter seem to be equivalent. PMID- 1511681 TI - Role and environment of the conserved Lys27 of snake curaremimetic toxins as probed by chemical modifications, site-directed mutagenesis and photolabelling experiments. AB - The positive charge of Lys27 was suppressed by chemical means in two short-chain curaremimetic toxins, namely erabutoxin a (Ea) from Laticauda semifasciata and toxin alpha from Naja nigricollis. This modification leads to a decrease in the binding affinity of the toxins for the nicotinic acetylcholine receptor, which range 6-15-fold, as judged from both the data reported here and those previously described in the literature. A negatively charged glutamate residue has been introduced at position 27 of erabutoxin a by site-directed mutagenesis. This change provokes a 120-fold decrease in the affinity, which reflects a major alteration of toxin-receptor cognate events. Using toxin-alpha derivative harbouring a photoactive group at Lys27, we probed the toxin local environment in a receptor-bound state by photocoupling experiments. The delta chain was the predominant coupling target, in contrast to previous observations indicating that a photoactive probe on Lys47 predominantly labelled the alpha chain. The toxin derivative weakly labelled the alpha and gamma chains but not the beta chain. The toxin may therefore interact with subunits other than the alpha chain, at least in the vicinity of Lys27. PMID- 1511683 TI - Regulation of the final phase of mammalian melanogenesis. The role of dopachrome tautomerase and the ratio between 5,6-dihydroxyindole-2-carboxylic acid and 5,6 dihydroxyindole. AB - The regulation of the final steps of the melanogenesis pathway, after L-2-carboxy 2,3-dihydroindole-5,6-quinone (dopachrome) formation, is studied. It is shown that both tyrosinase and dopachrome tautomerase are involved in the process. In vivo, it seems that tyrosinase is involved in the regulation of the amount of melanin formed, whereas dopachrome tautomerase is mainly involved in the size, structure and composition of melanin, by regulating to the incorporation of 5,6 dihydroxyindole-2-carboxylic acid (DHICA) into the polymer. Moreover, using L-3,4 dihydroxyphenylalanine (dopa) and related compounds, it was shown that the presence of dopachrome tautomerase mediates an initial acceleration of melanogenesis since L-dopachrome is rapidly transformed to DHICA, but that melanin formation is inhibited because of the stability of this carboxylated indole compared to 5,6-dihydroxyindole (DHI), its decarboxylated counterpart obtained by spontaneous decarboxylation of L-dopachrome. Using L-dopa methyl ester as a precursor of melanogenesis, it is shown that this carboxylated indole does not polymerize in the absence of DHI, even in the presence of tyrosinase. However, it is incorporated into the polymer in the presence of both tyrosinase and DHI. Thus, this study suggests that DHI is essential for melanin formation, and the rate of polymerization depends on the ratio between DHICA and DHI in the medium. In the melanosome, this ratio should be regulated by the ratio between the activities of dopachrome tautomerase and tyrosinase. PMID- 1511684 TI - Kinetic behaviour of alpha-chymotrypsin in reverse micelles. A stopped-flow study. AB - At the aim of investigating whether the early rapid phase of enzyme turnover is different in reverse micelles compared with bulk water, the kinetic properties of alpha-chymotrypsin have been studied in reverse micelles formed by sodium bis(2 ethylhexyl)sulfosuccinate in isooctane. Pre-steady state and steady-state kinetic constants, in water and in reverse micelles, have been determined by stopped-flow spectrophotometry for the hydrolysis of two substrates, namely acetyl-L tryptophan-p-nitrophenyl ester and p-nitrophenyl acetate. It has been shown that, for both substrates, the acylation rate constant (k2) is very much lower in reverse micelles than in water. However, the deacylation rate constant (k3) and the turnover number (kcat) are not significantly changed in reverse micelles with respect to bulk water. Therefore, despite considerable rate changes in the acylation step, deacylation is rate limiting both in water as well as in reverse micelles, under the experimental conditions used. PMID- 1511685 TI - Differential scanning calorimetry of chicken erythrocyte nuclei. AB - Investigation of structural features of native chromatin requires the use of intact nuclei, a turbid material which cannot be analyzed by optical methods. Differential scanning calorimetry does not require optically clear samples and has been proved by a number of authors to be a powerful tool in this field of study. By this technique, chicken erythrocyte nuclei were found to undergo at least four thermal transitions, centered at 59, 74, 88 and 98 degrees C. The highest temperature transition is strongly dependent on age and storage conditions of the nuclei. Adequate storage conditions overcame this problem and reproducible scans were obtained over a period of several months. This technical improvement has permitted the reconsideration of the occurrence of the fourth calorimetric transition, previously believed to be displayed only in replicating nuclei. Evidence gathered in the presence of perturbants and possible ligands allows the assignment of the four transitions to a nuclear protein scaffold, histones, nucleosomal DNA and a superstructured form of DNA. Moreover, it suggests that the higher-order structure is stabilized by fibronectin-like proteins. PMID- 1511686 TI - Formation of homogeneous carbohydrate-lectin cross-linked precipitates from mixtures of D-galactose/N-acetyl-D-galactosamine-specific lectins and multiantennary galactosyl carbohydrates. AB - Quantitative precipitation studies have shown that the Man/Glc-specific lectin concanavalin A (ConA) forms homogeneous (homopolymeric) cross-linked precipitates with individual asparagine-linked oligomannose and bisected hybrid-type glycopeptides in the presence of binary mixtures of the carbohydrates [Bhattacharyya, L., Khan, M. I. & Brewer, C. F. (1988) Biochemistry 27, 8762 8767]. The results indicate that the ConA-glycopeptide precipitates are highly organized cross-linked lattices that are unique for each carbohydrate. Using similar techniques, the present study shows that the Gal-specific lectins from Erythrina indica and Ricinus communis (agglutinin I) form homogeneous cross linked complexes with individual carbohydrates in binary mixtures of triantennary and tetraantennary complex-type oligosaccharides with terminal Gal residues. Conversely, binary mixtures of Gal/GalNAc-specific lectins from E. indica, Erythrina cristagalli, Erythrina flabelliformis, R. communis, soybean (Glycine max), and Wistaria floribunda (tetramer) in the presence of a naturally occurring or synthetic branched-chain oligosaccharide with terminal GalNAc or Gal residues provide evidence for the formation of separate cross-linked lattices between each lectin and the carbohydrate. The present results therefore demonstrate the formation of homogeneous lectin-carbohydrate cross-linked lattices in (a) a mixture of branched-chain complex-type oligosaccharides in the presence of a specific Gal/GalNAc-binding lectin, and (b) a mixture of lectins with similar physicochemical and carbohydrate binding properties in the presence of an oligosaccharide. These findings show that lectin-carbohydrate cross-linking interactions provide a high degree of specificity which may be relevant to their biological functions as receptors. PMID- 1511687 TI - Integration of early light-inducible proteins into isolated thylakoid membranes. AB - An in-vitro system has been established to study the integration of early light inducible proteins (ELIP) into isolated thylakoid membranes. The in-vitro expressed ELIP precursor proteins exist in two forms, a high-molecular-mass aggregate which is accessible to trypsin but no longer to the stromal processing protease and a soluble form which is readily cleaved to the mature form by the stromal protease. The mature form of ELIP is integrated into thylakoid membranes; its correct integration can be deduced from the observation that the posttranslationally transported products and the in-vitro integrated ELIP species are cleaved by trypsin to products of the same apparent molecular mass. Trypsin resistant fragments of high-molecular-mass and low-molecular-mass ELIP appear to have the same size. The processed ELIP species, as well as an engineered mature form of ELIP, are integrated into isolated thylakoid membranes. Integration of the mature protein occurs in the absence of stroma, into sodium-chloride-washed, and trypsin-treated thylakoid membranes. The process of integration is almost temperature independent over 0-30 degrees C. Analysis of the time course of integration leads to the conclusion that, under in-vitro conditions, processing but not integration into membranes is the rate-limiting step. In the absence of stroma, the ELIP precursor is bound to the thylakoid membranes, however, it is no longer accessible to the stromal maturating protease when added after binding has occurred. In conclusion, integration of ELIP differs in many essential details from that of its relatives, the light-harvesting chlorophyll a/b protein family. PMID- 1511688 TI - The three-dimensional structure of guanine-specific ribonuclease F1 in solution determined by NMR spectroscopy and distance geometry. AB - Two-dimensional 1H-NMR studies have been performed on ribonuclease F1 (RNase F1), which contains 106 amino acid residues. Sequence-specific resonance assignments were accomplished for the backbone protons of 99 amino acid residues and for most of their side-chain protons. The three-dimensional structures were constructed on the basis of 820 interproton-distance restraints derived from NOE, 64 distance restraints for 32 hydrogen bonds and 33 phi torsion-angle restraints. A total of 40 structures were obtained by distance geometry and simulated-annealing calculations. The average root-mean-square deviation (residues 1-106) between the 40 converged structures and the mean structure obtained by averaging their coordinates was 0.116 +/- 0.018 nm for the backbone atoms and 0.182 +/- 0.015 nm for all atoms including the hydrogen atoms. RNase F1 was determined to be an alpha/beta-type protein. A well-defined structure constitutes the core region, which consists of a small N-terminal beta-sheet (beta 1, beta 2) and a central five-stranded beta-sheet (beta 3-beta 7) packed on a long helix. The structure of RNase F1 has been compared with that of RNase T1, which was determined by X-ray crystallography. Both belong to the same family of microbial ribonucleases. The polypeptide backbone fold of RNase F1 is basically identical to that of RNase T1. The conformation-dependent chemical shifts of the C alpha protons are well conserved between RNase F1 and RNase T1. The residues implicated in catalysis are all located on the central beta-sheet in a geometry similar to that of RNase T1. PMID- 1511689 TI - Purification and properties of aminopeptidase H from chicken skeletal muscle. AB - Aminopeptidase H was purified from fresh chicken breast muscle by ammonium sulfate fractionation and successive chromatographies on DEAE-cellulose, Ultrogel AcA 34, activated thiol-Sepharose 4B, phenyl-Sepharose CL-4B and DEAE-cellulose again. The purified enzyme migrated as a single band on SDS/PAGE. Aminopeptidase H exhibits activity against both L-leucine beta-naphthylamide and alpha-N-benzoyl DL-arginine beta-naphthylamide. The molecular mass of this enzyme was found to be 52 kDa on SDS/PAGE and 400 kDa on Sepharose 6B column chromatography. The optimum pH for the hydrolysis of both substrates was 8.0 and this activity was remarkably enhanced by reducing agents. The enzyme was strongly inhibited by monoiodoacetate and leupeptin, but not affected by EDTA, phenylmethylsulfonyl fluoride, pepstatin, bestatin or puromycin. Aminopeptidase H has been shown to hydrolyze di , tri- and tetrapeptides in the manner of an aminopeptidase, as well as the beta naphthylamide derivatives of amino acids. However, the enzyme has not been shown to hydrolyze proteins such as hemoglobin, bovine serum albumin, myofibrillar proteins or sarcoplasmic proteins. PMID- 1511690 TI - Purification, phosphorylation and control of the guanine-nucleotide-exchange factor from rabbit reticulocyte lysates. AB - A simple, improved procedure for the isolation of guanine-nucleotide-exchange factor (GEF) and for eukaryotic initiation factor 2 (eIF-2) from rabbit reticulocyte lysates has been developed using ion-exchange chromatography on S Sepharose, Q-Sepharose, Mono Q and Mono S. The majority of the eIF-2 is separated from GEF at an early stage in the procedure and the remaining small amount of eIF 2.GEF complex is separated from the bulk of the GEF by FPLC on Mono S. The procedure yields approximately 2 mg each of eIF-2 and GEF, of 90% and greater than 80% purity, respectively, from the blood of ten rabbits. All fractions of purified GEF contain four subunits of molecular masses 84, 66, 54 and 39 kDa, with various amounts of a fifth, 30-kDa subunit. The modulation of GEF activity was investigated using the highly purified factor in a guanine-nucleotide exchange assay. The activity of GEF was stimulated by physiological concentrations of the polyamines, spermine and spermidine, but was unaffected by another polycationic compound, polylysine. Activity was also found to be inhibited by 1 mM NADP+ or NAD+, and this inhibition was overcome by the presence of 1 mM NADPH. Stoichiometric amounts of GEF were unable to release GDP from eIF 2.GDP complexes in the absence of free guanine nucleotides, suggesting that GEF operates by a ternary-complex mechanism. Casein kinase 1 or casein kinase 2 can each phosphorylate the largest subunit (84 kDa) of GEF. These enzymes both phosphorylate serine residues in GEF but they phosphorylate distinct sites, as demonstrated by phosphopeptide mapping following proteolytic or cyanogen bromide digestion. Neither of these kinases phosphorylated any of the other subunits of GEF to any significant extent and several other kinases were inactive against GEF. No effect of phosphorylation on activity could be demonstrated. PMID- 1511691 TI - The polygalacturonases of Aspergillus niger are encoded by a family of diverged genes. AB - Aspergillus niger produces several polygalacturonases that, with other enzymes, are involved in the degradation of pectin. One of the two previously characterized genes coding for the abundant polygalacturonases I and II (PGI and PGII) found in a commercial pectinase preparation was used as a probe to isolate five more genes by screening a genomic DNA library in phage lambda EMBL4 using conditions of moderate stringency. The products of these genes were detected in the culture medium of Aspergillus nidulans transformants on the basis of activity measurements and Western-blot analysis using a polyclonal antibody raised against PGI. These transformants were, with one exception, constructed using phage DNA. A. nidulans transformants secreted high amounts of PGI and PGII in comparison to the previously characterized A. niger transformants and a novel polygalacturonase (PGC) was produced at high levels by A. nidulans transformed with the subcloned pgaC gene. This gene was sequenced and the protein-coding region was found to be interrupted by three introns; the different intron/exon organization of the three sequenced A. niger polygalacturonase genes can be explained by the gain or loss of two single introns. The pgaC gene encodes a putative 383-amino-acid prepro protein that is cleaved after a pair of basic amino acids and shows approximately 60% amino acid sequence similarity to the other polygalacturonases in the mature protein. The N-terminal amino acid sequences of the A. niger polygalacturonases display characteristic amino acid insertions or deletions that are also observed in polygalacturonases of phytopathogenic fungi. In the upstream regions of the A. niger polygalacturonase genes, a sequence of ten conserved nucleotides comprising a CCAAT sequence was found, which is likely to represent a binding site for a regulatory protein as it shows a high similarity to the yeast CYC1 upstream activation site recognized by the HAP2/3/4 activation complex. PMID- 1511692 TI - A strong protein-tyrosine kinase activity is associated with a baculovirus expressed chicken tkl gene. AB - We have previously described a gene named tkl (tyrosine kinase related to lck). It belongs to the src family of protein-tyrosine kinases and among these it has significant homology to the lck gene (lymphoide cell kinase). The tkl gene product may represent the avian homolog of Lck, which is believed to participate in a lymphocyte-specific signal transduction pathway by association with a membrane receptor. To study the biochemical properties of the protein, a nearly complete tkl gene (isolated from a cDNA library from chicken spleen cells) was expressed in a baculovirus system. Approximately 10% of the extracted protein consisted of the soluble 51-kDa Tkl protein (p51tkl) at 40 h post-infection. This protein was found to be phosphorylated on tyrosine and serine residues at a ratio of 5:1. As expected, glycosylation or myristoylation could not be detected. Immunocomplex kinase assays indicated strong autophosphorylation of p51tkl at tyrosine residues and phosphorylation of exogenous substrates such as D glyceraldehyde-3-phosphate dehydrogenase (GAPDH), histones H2b and H4, and casein. This protein-tyrosine kinase activity also exhibited a marked preference for Mn2+ compared to Mg2+. The high level expression of enzymatically active Tkl should provide an excellent tool to further study the biological functions of this class of enzymes. PMID- 1511693 TI - Cytochemical and immunocytochemical characterization of a fibrillar network (GP2) in pancreatic juice: possible role as a sieve in the pancreatic ductal system. AB - The secretory product of the exocrine pancreas contains sedimentable and non sedimentable materials. Electron microscopy of the pellet obtained after ultracentrifugation reveals two major components: microvesicles (pancreasomes) and a fibrillar network of small mesh size. Negative staining of an unfixed pellet demonstrated that these structures are not fixation artifacts. Cytochemical analysis showed that pancreasomes are reactive to osmication and uranyl acetate staining, whereas the fibrillar network was unreactive thereby indicating that the latter does not contain lipids; however, lead citrate staining reveals the network. Alcian blue, known to bind sulfate groups of mucosubstances, reacted strongly with the fibrillar network. The pellet was also characterized by immunocytochemistry with specific antibodies to amylase and glycoprotein 2 (GP2). Both antibodies were located only on the fibrillar network. Washing of the pellet with 100 mM KCl-250 mM NaBr had little effect on GP2 content, but reduced considerably alpha-amylase associated with the reticular matrix. It appeared that GP2 was the major component of the scaffolding that gives rise to the fibrillar network and that other proteins such as alpha-amylase could reversibly bind to it. When double-labeling immunocytochemistry was carried out on the unwashed pellet, labeling of the first antigen reduced the labeling of the second. Removal of amylase by washing the pellet increased the GP2 signal. These results indicate that amylase is bound on the GP2 network. Although the function of the GP2 network is still not clearly defined several possibilities could be envisaged at the level of the pancreatic duct system: 1) The network could drain off any aggregates or precipitates forming in small ducts. 2) The small mesh of the network would present a physical barrier to infecting bacteria that could enter into the duct system from the intestine, especially in conditions of low flow rates. 3) The network may exert a mechanical pressure on the membranes bordering the acinar lumen and small ducts thereby preventing their collapse in basal conditions. PMID- 1511694 TI - Turnover of peroxisomal vesicles by autophagic proteolysis in cultured fibroblasts from Zellweger patients. AB - Previous studies have shown that in fibroblasts from patients with the Zellweger syndrome (ZS) aberrant membrane structures are present which contain peroxisomal membrane proteins (Santos, M. J. et al., Science 239, 1536-1538 (1988)). In order to characterize these structures we have performed double labeling immunoelectron microscopy experiments using antisera directed against the 69 kDa peroxisomal integral membrane protein (PMP) and lysosomal hydrolases. The results indicate that at least 80% of the structures earlier referred to as 'peroxisomal ghosts' contain lysosomal hydrolases. In addition, we have studied the effect of culture of ZS fibroblasts in the presence of 3-methyladenine, an inhibitor of autophagy, on the intracellular distribution of the 69 kDa PMP. Immunofluorescence experiments showed that in the presence of 3-methyladenine there is an increase in fluorescent spots and a change in the distribution of the spots from mainly perinuclear to randomly distributed throughout the cytoplasm. Double labeling immunoelectron microscopy revealed that after culture in the presence of 3 methyladenine the 69 kDa PMP also accumulates mainly in compartments containing lysosomal hydrolases. In one ZS cell line we found that after culture in the presence of 3-methyladenine there was also an accumulation of structures which were as small as normal microperoxisomes. We conclude that in ZS fibroblasts the 69 kDa PMP is mainly present in lysosomal compartments, presumably degradative autophagic vacuoles. Furthermore, in ZS fibroblasts peroxisomes of apparently normal morphology may be synthesized, but they are degraded by autophagic proteolysis. PMID- 1511696 TI - Chondrogenic differentiation in chick embryo osteoblast cultures. AB - Expression of specific differentiation markers was investigated by histochemistry, immunofluorescence, and biosynthetic studies in osteoblasts outgrown from chips derived from tibia diaphyses of 18-day-old chick embryos. The starting osteoblast population expressed type I collagen and alkaline phosphatase in addition to other bone and cartilage markers as the lipocalin Ch21; the extracellular matrix deposited by these cells was not stainable for cartilage proteoglycans, and mineralization was observed when the culture was maintained in the presence of ascorbic acid, calcium and beta-glycerophosphate. During culture, clones of cells presenting a polygonal chondrocyte morphology and surrounded by an Alcian-positive matrix appeared in the cell population. Type II collagen and type X collagen were synthesized in these areas of chondrogenesis. In addition, chondrocytes isolated from these cultures expressed Ch21 and alkaline phosphatase. Chondrocytes were generated also from homogeneous osteoblast populations derived from a single cloned cell. The coexistence of chondrocytes and osteoblasts was observed during amplification of primary clones as well as in subclones. The data show the existence, within embryonic bone, of cells capable in vitro of both osteogenic and chondrogenic differentiation. PMID- 1511695 TI - Independent expression and assembly properties of heterologous lamins A and C in murine embryonal carcinomas. AB - The majority of cells derived from adult mammalian tissues contain three major species of nuclear lamin proteins, A, B and C. In contrast, embryonic cells including undifferentiated murine embryonal carcinomas, contain only B-type lamins, A and C appearing only after differentiation. Human lamins A or C have been introduced by transfection into undifferentiated P19 embryonal carcinomas. Twenty-four hours after transfection, both of these proteins were found to independently associate with the nuclear envelope as judged by immunofluorescence microscopy and at the same time were associated with a salt-resistant structure having solubility properties similar to those of the nuclear lamina. Biosynthetic experiments indicated that heterologous lamin A underwent processing to its mature molecular weight, an event which in adult type cells occurs after assembly into the lamina. Observations on mitotic cells demonstrate that either of the two human lamins will, independent of the other, become dispersed throughout the cytoplasm during prophase and subsequently reassemble at the nuclear periphery during telophase. Nuclear lamins A and C are not, however, equivalent in their abilities to incorporate into the nuclear lamina in these cells. Experiments involving cells arrested in S phase using thymidine suggest that lamin C, but not lamin A, requires progression through the cell cycle and probably mitosis for assembly into the nuclear lamina of P19 EC cells. PMID- 1511697 TI - Effect of PDGF-AB heterodimer on a corneal epithelial cell line. AB - Exposure of cells of a rabbit corneal epithelial cell line (SIRC) to platelet derived growth factor-AB heterodimer (PDGF-AB) resulted in a rapid and transient elevation of cytosolic free calcium concentration with a maximum at 2 to 3 min after stimulation. The kinetics of the calcium response were dose-dependent, e.g., higher concentrations of PDGF-AB caused a faster rise in cytosolic free calcium concentration. Maximum response was achieved with 10 ng/ml PDGF; higher concentrations up to 100 ng/ml did not further enhance cytosolic free calcium concentration. The ED50 was calculated to be 5 ng/ml PDGF-AB. After complexing extracellular calcium, PDGF-AB still caused a significant rise in cytosolic free calcium concentration indicating a mobilization of calcium from intracellular stores. This rise, however, was less pronounced than in the presence of extracellular calcium. The elevation in cytosolic free calcium concentration was not accompanied by an increased mitotic or proliferative activity of the cells as checked by [3H]thymidine incorporation and counting of cell numbers after 3 days of continuous incubation with various concentrations of PDGF-AB or by alterations in cell size and cell volume. In contrast, alterations in cell shape with a remarkable amount of rounded and partially detached SIRC cells after addition of PDGF-AB were observed within 24 h. Moreover, PDGF-AB caused a reversible distortion of cytoskeletal components such as actin-containing microfilament bundles, microtubules, and vimentin filaments. The results suggest that PDGF-AB may act only as a competence factor for the stimulation of SIRC cells via modification of the intracellular calcium homeostasis. PMID- 1511698 TI - Coupled down-regulation of the RB retinoblastoma and c-myc genes antecedes cell differentiation: possible role of RB as a "status quo" gene. AB - The ability of the well known morphogen, retinoic acid (RA), as well as 1,25 dihydroxy-vitamin D3 (VD), whose receptor complex binds a DNA consensus sequence related to that of the retinoic acid receptor, to regulate expression of the retinoblastoma (RB) tumor suppressor gene in a context of induced cell differentiation was characterized. HL-60 human promyelocytic leukemia cells were induced to undergo myeloid or monocytic terminal cell differentiation by these agents. To investigate the potential coupling between down-regulation of RB and c myc oncogene expression with cell differentiation, dose response relationships for the induced down-regulation of RB and c-myc expression were compared with each other and with induced cell differentiation. The total amount of RB protein per cell increased as cells advanced through the cell cycle, but the amount of RB protein relative to the total cell mass remained approximately constant. Treated with RA or VD, an early progressive decrease in cellular content of the RB protein occurred in all cell cycle phases well before any cell cycle modulation or phenotypic differentiation. For a differentiation-defective variant HL-60 cell line, failure to differentiate was preceded by a failure to down-regulate cellular levels of the RB protein. In dose response experiments, progressively increasing RA or VD concentrations caused progressively greater reductions in RB as well as c-myc expression with an increasing fraction of cells terminally differentiating. For both RA and VD, the dose response relationships for reductions in RB and c-myc expression were similar suggesting that their down regulation may be coupled. These observations are consistent with a model whereby RB expression acts as a cellular brake to sustain a developmentally ordained state of differentiation (i.e., preserve the "status quo"); and the down regulation of heterogeneously distributed RB protein per cell below a threshold is part of the metabolic cascade culminating in terminal cell differentiation. Thus, RB may have a role in this developmental context. PMID- 1511699 TI - Study of the function and regulation of liver N-CAM in Xenopus laevis. AB - The liver of Xenopus laevis is a unique exception in terms of the cell adhesion molecules (CAM) which it expresses. In most species, hepatocytes are characterized by the expression of the epithelial Ca(2+)-dependent CAM E-cadherin or of closely related variants of this molecule (e.g., L-CAM); in Xenopus liver, however, the levels of expression of epithelial cadherins is very low while a thyroxine-inducible isoform of N-CAM is expressed in postmetamorphic hepatocytes. Since Xenopus liver N-CAM is localized in regions of contact between hepatocytes, it has been proposed that it might be involved in mediating hepatocyte adhesion in this species. In this study, we demonstrate that N-CAM can indeed act as a functional adhesion molecule in the liver of Xenopus and that its expression is correlated with a number of profound morphological changes of this organ. After thyroxine treatment, hepatocytes are no longer organized in long loose cords but in compact lobules of cells. Furthermore, at the ultrastructural level, plasma membranes are in much closer proximity with the appearance of electron-dense material in areas of closer contact. We have established two novel culture systems for premetamorphic Xenopus hepatocytes as adherent and non-adherent cells, and we describe the induction of expression of N-CAM in these cells. Given the difference in the profile of adhesion molecules present in the liver of Xenopus and of other species, our results are discussed in view of the importance of the expression of a specific set of cell adhesion molecules in defining the development of homologous organs in different species. PMID- 1511700 TI - Gamma-interferon inhibits extracellular matrix synthesis and remodeling in collagen lattice cultures of normal and scleroderma skin fibroblasts. AB - Three-dimensional collagen lattice cultures of fibroblasts mimic the in vivo situation better than monolayer cultures. Here, skin fibroblasts from scleroderma patients and healthy controls were cultivated in collagen lattices, and the effects of recombinant human gamma-interferon (IFN-gamma) on these cultures investigated. IFN-gamma inhibited collagen lattice retraction in a dose-dependent way at concentrations ranging from 10 to 10,000 U/ml. This effect was independent of any alteration to the cell proliferation within the lattices. The inhibition was of the same order of magnitude in normal and pathological fibroblasts. The synthesis of collagen and non-collagen proteins, particularly fibronectin, was increased in scleroderma cultures. It was inhibited in both normal and scleroderma fibroblasts by IFN-gamma, with a maximal effect at the concentration 1000 U/ml, but the inhibition of protein synthesis was far more intense in scleroderma than in normal cells. In situ hybridization, Northern blot and dot blot analyses showed that mRNA coding for pro alpha 1(I) collagen was decreased in IFN-gamma-treated cells, indicating an effect at the pretranslational level. IFN-gamma also inhibited glycosaminoglycan synthesis, but in scleroderma cells only. This study shows that IFN-gamma regulates cell behavior in three dimensional collagen matrices: (i) it decreases protein and specifically glycosaminoglycan synthesis in scleroderma fibroblasts, (ii) it modulates the interactions between cells and matrix that lead to the retraction of the lattice. Whereas collagen synthesis is largely decreased in lattice cultures like in vivo, it remains increased in the case of scleroderma compared to normal fibroblasts and may be down-regulated by IFN-gamma. Similar conclusions may be drawn for fibronectin and glycosaminoglycans. The inhibitory effect of IFN-gamma on the retraction capacity of fibroblasts and on their ability to synthesize increased amounts of extracellular matrix macromolecules may be of potential interest for therapeutic use of IFN-gamma in scleroderma patients. PMID- 1511702 TI - Fractionation of human neutrophils into subpopulations by countercurrent distribution: surface charge and functional heterogeneity. AB - Isolated blood neutrophils from normal healthy subjects were separated into fractions by sequential countercurrent distribution (CCD) in a charge-sensitive dextran/polyethylene glycol aqueous phase system. The neutrophils separated as a broad profile, and in a charged phase procedure the separation was based upon differences in cell surface electrokinetic properties, as confirmed by electrophoretic mobility measurements of fractions across the profile using analytical cytopherometry. The CCD cell fractions were generally pooled as three or four major subfractions for analysis of functional and metabolic differences. These included measurements of chemotaxis, phagocytosis, and respiratory burst. An inverse relationship was found between the electrophoretic mobility (EPM) of the subfraction pools and their functional competence, with the less electronegative cell fraction pools often as much as 2 to 3-fold more active than the more electronegative pools. This demonstration of electrokinetic and functional heterogeneity in 'resting' neutrophil subpopulations separated by CCD may reflect changes during their sojourn in the circulation that determine selective margination and recruitment of cells to inflammatory foci and sites of infection. PMID- 1511701 TI - Effect of monoclonal antibodies to defined regions of tropoelastin on elastogenesis in vitro. AB - Primary cultures of chick embryo aorta cells were grown for one week in the presence of mouse monoclonal antibodies directed against defined regions of chick tropoelastin. This treatment did not significantly alter cell proliferation, cell viability and incorporation of labeled amino acids into total protein or tropoelastin compared with control cultures in which antibodies were either omitted or substituted with an unrelated monoclonal antibody. Tropoelastin reactive material in the cell layer was revealed by immunologic staining with rabbit antibodies against the chick protein both at the optical and ultrastructural level. Immunofluorescence of control cultures showed that tropoelastin was incorporated into thin and straight fibrils which were sometimes associated with spot-like elements. In the electron microscope tropoelastin reactive sites were found mainly on the amorphous core of typical, small elastic fibers. The morphological picture of tropoelastin deposits in cultures exposed to anti-tropoelastin monoclonal antibodies depended on the molecular form (whole antibody or Fab fragments) and the binding specificity of the antibody used. Although alterations common to different antibodies were observed, the main structural features were peculiar for each antibody. Two antibodies which bound epitopes present in two regions of tropoelastin grossly altered the formation of amorphous elastin. Moreover, two antibodies directed against the region of tropoelastin containing the polypentapeptide-repeat (VPGVG)n stimulated the deposition of the protein into the amorphous core of normal-looking elastic fibers and disorganized the compact bundles of parallel microfibrils seen in controls. Finally, one antibody which recognized a unique epitope close to the carboxy-terminal end of tropoelastin and Fab fragments from all antibodies apparently inhibited the formation of the amorphous nuclei of elastic fibers, but not the association of tropoelastin with microfibrils. The data suggest that the association of tropoelastin molecules during fiber assembly is not random, but follows an ordered alignment process which the antibodies alter by imposing a different molecular packing. PMID- 1511703 TI - Immunocytochemical localization of alkane-inducible cytochrome P-450 and its NADPH-dependent reductase in the yeast Candida maltosa. AB - Antibodies directed against cytochrome P-450Cm1 and the NADPH-cytochrome P-450 reductase were used to study the induction and intracellular localization of these components of the alkane monooxygenase system in the yeast Candida maltosa. Transition from glucose to n-hexadecane utilization resulted in an about 100-fold increase of the immunodetectable P-450 form whereas the reductase was only moderately induced by a factor of about 5. P-450 but not the reductase was further increased by oxygen limitation during cultivation on n-hexadecane. Using an immunogold technique on ultrathin cryosections, P-450 was found to be concentrated in the nuclear envelope during the early phase of the induction process. However, after maximal induction, the highest labeling was observed in membranes of the endoplasmic reticulum closely associated with the peroxisomes and the plasma membrane. Double-labeling experiments revealed that P-450 and its reductase were distributed in the same regions of the endoplasmic reticulum. PMID- 1511704 TI - Clostridium difficile toxin A induces multinucleation in the human leukemic T cell line JURKAT. AB - Clostridium difficile toxin A is a cytotoxic enterotoxin known to be active on all mammalian cell lines tested up to now. It induces a disruption of the cytoskeleton, particularly the microfilament system, leading to inhibition of cell proliferation. Here, we describe some effects of toxin A on the leukemic T cell line JURKAT. Cells exposed to the toxin did not divide, as cell numbers remained constant for 3 days in the presence of 0.5 to 1.0 micrograms/ml of the toxin. However, these cells were found to become multinucleated, a phenomenon which was time- and dose-dependent. After treatment for 72 h with 0.5 micrograms/ml toxin A, 95% of the cells were multinucleated and had a considerably increased cell diameter. These effects in JURKAT cells were partially reversible upon removal of the toxin within 12 h after the beginning of toxin exposure, but irreversible after 24 h of toxin treatment. These results suggest a continuing nuclear division in the absence of cytoplasmic division, i.e., an effect of toxin A on contractile ring formation. The JURKAT cell is the first cell type reported to respond to toxin A with multinucleation. PMID- 1511705 TI - The molecular architecture of an insect midgut brush border cytoskeleton. AB - The cytoskeletal apparatus of the vertebrate intestinal brush border (BB) has served as a model system for the actin-based cytoskeleton of nonmuscle cells. In this study, we examine the structural organization and molecular architecture of the BB cytoskeleton expressed in the midgut of lepidopteran larvae, Manduca sexta. Electron microscopy of the midgut of the 5th instar larvae revealed enterocytes with an apical BB surface comparable to that in the vertebrate intestine, with both microvillar (MV) and terminal web (TW) domains, the latter defined by a zone of organelle exclusion directly beneath the MV. As reported previously for the larval dragon fly, the MV contain a bundle of actin filaments, as determined by staining with rhodamine phalloidin (Kukulies, J., et al., Protoplasma 121, 157-162 (1984)) and heavy meromyosin decoration (Komnick, H., J. Kukulies, Zoomorphology 107, 241-253 (1987)). Two-dimensional gel analysis revealed the presence of multiple isoelectric variants of actin with the major isoform corresponding to the non-muscle actin isoform II, expressed in Drosophila. Like the vertebrate BB, the Manduca BB can be isolated intact from enterocytes by mechanical shear. Immunochemical analysis of isolated BB fractions or whole homogenates of midgut revealed proteins of appropriate molecular weight immunoreactive with antibodies to the MV core proteins: BB myosin I, villin and fimbrin, and the TW components: spectrin, myosin II and tropomyosin. Immunocytochemical localization of a subset of these proteins at the light microscopic (spectrin) and electron microscopic (actin, villin, spectrin, myosin II, and tropomyosin) level reveals that the molecular architecture of the Manduca BB cytoskeleton is homologous to that found in vertebrates. PMID- 1511706 TI - SVS II--an androgen-dependent actin-binding glycoprotein in rat semen. AB - Rat seminal vesicles and the lateral prostate secrete a glycoprotein designated as SVS II in an androgen-dependent manner. SVS II, which has a M(r) of 49,000 and a pI of 10.5, is an actin-binding protein. G- and F-actins cosediment with SVS II at a ratio of 2:1 (actin:SVS II). SVS II affects the kinetics of actin polymerization in the same way as do barbed end capping proteins. Interaction with actin is specific for the skeletal and cardiac muscle isoforms and there is no corresponding interaction with cytoplasmic actins. The binding site is close to the C-terminus of actin. Monospecific polyclonal antibodies directed against the N-terminus of actin cross-react with SVS II, but there is no cross-reaction by a monoclonal antibody directed against a C-terminal epitope on actin. Recent sequence analysis of SVS II shows a sequence of about 14 residues that is repeated 13 times between residues 86 and 298. The consensus sequence based on these repeats is homologous to residues 10 to 25 of actin; this may account for the immunological cross-reactivity. Like actin, SVS II binds and inhibits the activity of DNase I, but SVS II has no effect on the ATPase activity of myosin subfragment 1. Thus, SVS II is an actin-binding protein which retains some properties of actin itself. PMID- 1511707 TI - Swelling of Golgi apparatus of bovine mammary epithelial cells in response to monensin treatment requires fixation. PMID- 1511708 TI - Early diagnosis in ovarian pathology. PMID- 1511709 TI - Role of vaginal surgery in the 1st stage endometrial cancer. Experience of the Florence School. AB - The role of vaginal surgery in first stage endometrial carcinoma is reviewed. Out of total of 231 patients with endometrial cancer, observed at the Gynecologic Clinic of Florence from 1977 to 1981, 187 were at Stage I and 180 of them were submitted to surgery. During the period 1977-1979, the treatment protocol recommended vaginal hysterectomy; since 1980 abdominal surgery has prevailed. Depending on risk factors, adjunctive radiotherapy was employed. No statistically significant difference was observed in the actuarial survival curves between different surgery routes. However, severe complications and operative mortality was significantly lower in patients operated by vaginal hysterectomy. The vaginal route may be considered an adequate alternative therapy for endometrial carcinoma Stage I. PMID- 1511710 TI - Organization of the screening programme in Bialystok Province. AB - This paper describes the new "model" of the cervical cancer screening introduced as pilot study in the Bialystok Province. The new programme was carried out to choose which "model" was better: computerized monitoring and invitation to the women to the outpatient clinic for the Pap-test performed by screeners on full integration into gynecologic health care. The new system introduced in the chosen outpatients clinics increased the acceptance (of the screening) by women especially in younger age groups. PMID- 1511711 TI - Surgical pathological staging of endometrial carcinoma and results of treatment. AB - 114 women with endometrial carcinoma at clinical stage 1 to 3 were treated with surgery as first line of treatment. Patients were classified as being low or high risk on the basis of the surgical pathological patterns of the tumor. Disease limited to the uterine body, G1-G2 tumors and myometrial invasion of less than 1/3, identified low risk patients which received no adjuvant therapy. All the others were considered high risk and treated with radiation therapy. Patients were retrospectively restaged according to 1988 FIGO guidelines and survival was analyzed. Cox's proportional hazards method was employed to identify independent prognostic factors. Disease free survival (DFS) was 90% for stage 1, 83% for stage 2, and 43% for stage 3 patients. Lymphatic spread was associated to the poorer prognosis. Proportional hazards model showed that tumor grading, myometrial invasion and lymphatic spread were significantly related to the time of relapsing. Low risk patients showed better outcomes despite not having received adjuvant treatment, thus post-operative therapy is not indicated in this subset of patients. Radiation adjuvant therapy for high risk patients did not give satisfactory results. Failures were observed both locally and distantly calling for new adjuvant strategies. Surgical pathological staging of endometrial cancer is currently mandatory. Retroperitoneal lymph node sampling is indicated in patients with high risk pre- (advanced clinical disease, undifferentiated tumors) or intra-operative (deep myometrial invasion, enlarged pelvic nodes) prognostic factors. All prognostic indicators must be obtained from surgery and pathology in order to assess the risk of relapse. PMID- 1511712 TI - Cisplatin-based combination chemotherapy with or without doxorubicin in advanced epithelial ovarian cancer: 8-year update of a randomized multicentric clinical trial. The Gruppo Oncologico Nord Ovest (GONO). AB - One hundred and twenty-five patients with advanced epithelial ovarian cancer (EOC) were postsurgically included in a multicentric clinical trial comparing the association of cisplatin (CDDP) (50 mg/m2 iv day1) + cyclophosphamide (CTX) (600 mg/m2 iv day 1) (PC regimen) versus the combination of PC + doxorubicin (ADM) (45 mg/m2 iv day 1) (PAC regimen), repeated every four weeks. After the sixth course of chemotherapy, patients without clinical evidence of disease or with surgically resectable residual disease (RD) underwent second-look laparotomy. Afterwards patients in surgical complete response (sCR) stopped chemotherapy, while partial responders or patients with stable disease received six more courses of the same regimen used as first-line treatment. Among the 67 patients with measurable RD, PAC regimen achieved a better clinical complete response (40.6% vs 20.0%); the difference approached statistical significance. In the 75 patients who underwent second-look laparotomy, PAC regimen induced a significantly higher sCR rate (62.2% vs 39.5%, p less than 0.05). The median survival (S) and progression free survival (PFS) were better in PAC arm, even if the differences were not statistically significant. Eight-year S and 8-year PFS were 32.7% and 24.7% respectively, for PAC arm, and 23.9% and 14.1%, respectively, for PC arm. These data seem to confirm the clinical advantage provided by the addition of ADM to PC regimen in the treatment of advanced EOC. PMID- 1511713 TI - Intracystic carcinoma of the breast. Our experience. AB - Malignant tumours of the breast occurring as cysts present an incidence from 0.3% to 0.7%. The Authors report their experience during 15 years in 470 patients with carcinoma of the breast. Endocystic carcinoma appeared in 0.6% of patients: the diagnosis is not always possible with cytology, but ultrasound scans make possible to identiphy cysts which have to undergo biopsy because solid areas within the cystic cavity have been detected. In this case surgery is advised even if the cytological examination has been negative. PMID- 1511714 TI - Prognostic factors in epithelial ovarian cancer. AB - In the present study the Authors have statistically evaluated the influence of the main prognostic factors in 160 women affected by epithelial ovarian cancer. They were sequentially observed at Oncologic Institute of Bari, Italy from december 1981 to december 1989. The prognostic factors (age, stage, grading, histological type, performance status and residual disease), have been evaluated through an actuarial analysis of survival and compared with those reported by many authors in literature. Our data confirm the relevance, among all, of the grading, the clinical stage and residual disease as traditional parameters. Furthermore it is proposable the use of new prognostic factors such as nuclear ploidy and proliferative activity (S-phase, labeling index). PMID- 1511715 TI - Quality of life and neoplastic diseases. Ethical issues. AB - The article analyses the concept of the quality of life comparing two different ethical approaches, that is "catholic" personalist bioethics and "lay" bioethics. As regards the oncological field, personalist bioethics defends the respect for life as an absolute value (sanctity of life), while "lay" bioethics focuses attention on the patient's autonomy. The authors think that in oncological therapies the subjective evaluation of the patient must be taken into consideration as the expression of his/her personal concept of the quality of life, always with priority of the respect of life. PMID- 1511716 TI - Multiparametric discrimination of serous ovarian tumors by analytical morphometry. AB - In order to enhance the discrimination power in the field of serous ovarian tumors, we applied the software system SAM (Shape Analytical Morphometry) to the analytic studies of biological forms. Besides the usual dimensional evaluations (perimeter, area, maximum diameter and shape index), this procedure permits the description of the nuclear form using analytical parameters: 1) extraction of nucleus fundamental curve; that is a functional curve giving the "smoothing" of the original contour by two parametric equations (separately for x and y values as independent variables); 2) evaluation of nuclei contour irregularities by Fourier analysis; 3) evaluation of shape asymmetry by SAE (Shape Asymmetry Evaluator); that is the ratio between the length of a segment of a parabola interpolating the original curve points, and a straight line joining its extremities for a 180 degrees barycentric rotation according 10 degrees steps. All parameters resulted to be independent and were submitted to multivariate discriminant analysis. We studied 180 nuclei from 18 cases of serous ovarian tumors, (6 benign, 6 borderline and 6 malignant tumors). With respect to the dimensional parameters, the application of analytical morphometry permitted us to reduce the minimum percentage error in the discrimination of the different classes. In fact, in the distinctions of benign and malignant nuclei, the minimum percentage error was 13.30%, against the 18.3% error when using dimensional morphometry. Furthermore, in the comparison of malignant and borderline nuclei there was a reduction of error from 23.3% to 22.5%, and in the comparison of benign and borderline nuclei, the error was reduced from 37.5% to 30%.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1511717 TI - Analysis of the prognostic factors of endometrial carcinoma. A retrospective study of 144 patients. AB - One hundred and fourty-four patients with endometrial carcinoma who had undergone surgery as primary treatment were retrospectively studied from January 1980 to September 1990 for the purpose of correlating the survival rate with known or presumed prognostic factors. The patients averaged 63.1 years of age (range 32-88 years); 106 were classified as having Stage I disease, 10 Stage II, 16 Stage III and 2 Stage IV. Histology confirmed pure adenocarcinomas in 77%, adenosquamous carcinoma in 3.5%, clear cell carcinomas in 2.5% and serous papillary in 17%. Surgical treatment consisted of extrafasial hysterectomy with pelvic lymphadenectomy up to the aortic bifurcation in 69 patients (48%), Wertheim's hysterectomy in 10 (7%), simple or vaginal hysterectomy in the remaining 65 patients (45%). Five-year survival rate in all the case series was 74.3% whereas for patients with Stage I carcinoma it was 79.9%. Different prognostic factors were correlated in a multivariate analysis with the outcome of the disease. Myometrial invasion presented a mortality ODDS RATIO (OR) of 3.18 (95% CI 1.25 8.06), for histologic grade OR 4.33 (95% CI 1.74-10.74) and for stage (2-3 vs 1) OR of 2.73 (95% CI 1.09-6.83) demonstrating a high significance, whereas pregnancy, excess body weight, age and histotype were not considered as relevant factors for prognosis. For age we found mortality OR 2.54 (95% CI 0.75-8.59) for women greater than 55y. PMID- 1511718 TI - Inflammatory carcinoma of the breast. AB - Inflammatory breast carcinoma has to be defined by accurate clinical and pathological criteria. The prognosis is very poor and improvements made by chemotherapy are limited to the increase in the disease-free period and overall survival for a few months. PMID- 1511719 TI - Carbon dioxide laser surgery in colposcopy for cervicovaginal intraepithelial neoplasia treatment. 10 years experience and failure analysis. AB - CO2 laser vaporisation is an effective method in the treatment of cervico-vaginal pre-invasive lesions. In a case-series of 334 patients no case of invasive neoplasia development were registered at longterm follow-up. The failure rate is comparable to those described with traditional surgical methods and are due to the particular topography of the disease. PMID- 1511720 TI - Serum levels of TAG 72 and CA 15.3 in patients with gynaecological neoplasms. AB - In the present report we have evaluated two new serum tumour markers identified by monoclonal antibodies: TAG 72 and CA 15.3 in 62 patients with gynaecological carcinomas, in prevalence ovarian and 36 women with benign gynaecological diseases. Serum levels of both markers were determined using two immunoradiometric assays and the cut-off values were set at 5 U/mL for TAG 72 and at 40 U/mL for CA 15.3. In our study the sensitivity was 57% for TAG 72 and 43% for CA 15.3 with a specificity of 97% and 89% respectively. Even if these two markers show a sensitivity lower than CA 125, these preliminary results seem to suggest the possible role of TAG 72 and CA 15.3 both as confirmatory tests and as adjunctive tests, especially the first for its excellent specificity. PMID- 1511721 TI - Quality of life in gynaecological oncology. The personalist perspective of bioethics. AB - Quality of life in gynaecological neoplastic diseases assumes a specific role within the therapeutic choice. Gynaecologists must give attention to the possibility of the patient's identity crises: a woman's reconstruction of her psycho-physical identity as regards gynaecological cancer is particularly difficult. Psychological assistence acquire a relevant role in improving the patient's quality of life. Personalist bioethics proposes a concept of corporeity which considers body not only in the physical aspect but also as an expression of subjectivity and totality of the person. PMID- 1511722 TI - Tumor necrosis factor and soluble interleukin-2 receptor: two immunological biomarkers in female neoplasms. AB - In this study we have evaluated two new immunological parameters, soluble IL-2 receptor (s IL-2 R) and TNF, in 119 patients with female solid neoplasms (47 ovarian and 72 breast cancer). Our data demonstrate that both these markers have mean serum levels in cancer patients higher than in normal population, particularly in ovarian cases. Also the overall positivities were higher in ovarian (68%) than in breast cancer (51%). Finally we observed no relevant differences according to the status of disease in both groups of cancer patients. These preliminary results could suggest the possible usefulness of an immunological monitoring in cancer patients, above all when an immunotherapy with biological responder modifiers is proposed. PMID- 1511723 TI - Regional surgery in advanced ovarian carcinoma. AB - Regional surgery can be defined as "the maximum cytoreduction of all macroscopic tumors developing in the abdominal cavity". The Authors present their experiences with this difficult technique and conclude that regional surgery can improve prognosis. PMID- 1511724 TI - Surgical treatment of invasive carcinoma of the vulva. A reappraisal. AB - The Authors studied three groups of patients affected by invasive vulvar carcinoma. The first group (19 cases), treated by radical vulvectomy and bilateral inguinal lymphadenectomy, had a survival rate at 5 years of 89% in Stage I and 56% in Stage II. The second group (9 cases) which presented poor general health conditions, had a survival rate at 4 years of 33% and 14% in Stage I and in Stage II, respectively. The third group of patients (7 cases), who refused any type of treatment, died within 12 months. Nodal involvement influenced survival rate. In fact, regardless of the stage, a survival rate at 5 years of 92% and 26% was seen in patients with negative nodes and positive nodes, respectively. In conclusion, the study confirms that radical surgery is the therapy of choice in advanced carcinoma of the vulva. However, early diagnosis remains the most important agent in reducing the extension of the surgical treatment. PMID- 1511725 TI - Identification of multiple active growth factors in basement membrane Matrigel suggests caution in interpretation of cellular activity related to extracellular matrix components. AB - We have recently demonstrated the formation of interconnecting canalicular cell processes in bone cells upon contact with basement membrane components. Here we have determined whether growth factors in the reconstituted basement membrane (Matrigel) were active in influencing the cellular network formation. Various growth factors including transforming growth factor beta (TGF-beta), epidermal growth factor (EGF), insulin-like growth factor 1, bovine fibroblast growth factor (bFGF), and platelet-derived growth factor (PDGF) were identified in Matrigel. Exogenous TGF-beta blocked the cellular network formation. Conversely, addition of TGF-beta 1 neutralizing antibodies to Matrigel stimulated the cellular network formation. bFGF, EGF, and PDGF all promoted cellular migration and organization on Matrigel. Addition of bFGF to MC3T3-E1 cells grown on Matrigel overcame the inhibitory effect of TGF-beta. Some TGF-beta remained bound to type IV collagen purified from the Engelbreth-Holm-Swarm tumor matrix. These data demonstrate that reconstituted basement membrane contains growth factors which influence cellular behavior, suggesting caution in the interpretation of experiments on cellular activity related to Matrigel, collagen type IV, and possibly other extracellular matrix components. PMID- 1511726 TI - Collagen fibril assembly by corneal fibroblasts in three-dimensional collagen gel cultures: small-diameter heterotypic fibrils are deposited in the absence of keratan sulfate proteoglycan. AB - Extracellular matrix assembly is a multistep process and the various steps in collagen fibrillogenesis are thought to be influenced by a number of factors, including other noncollagenous matrix molecules. The synthesis and deposition of extracellular matrix by corneal fibroblasts grown within three-dimensional collagen gel cultures were examined to elucidate the factors important in the establishment of tissue-specific matrix architecture. Corneal fibroblasts in collagen gel cultures form layers and deposit small-diameter collagen fibrils (approximately 25 nm) typical of the mature corneal stroma. The matrix synthesized contains type VI collagen in a filamentous network and type I and type V collagen assembled as heterotypic fibrils. The amount of type V collagen synthesized is relatively high and comparable to that seen in the corneal stroma. This matrix is deposited between cell layers in a manner reminiscent of the secondary corneal stroma, but is not deposited as densely or as organized as would be found in situ. No keratan sulfate proteoglycan, a proteoglycan found only in the corneal stroma, was synthesized by the fibroblasts in the collagen gel cultures. The assembly and deposition of small-diameter fibrils with a collagen composition and structure identical to that seen in the corneal stroma in the absence of proteoglycans typical of the secondary corneal stroma imply that although proteoglycan-collagen interactions may function in the establishment of interfibrillar spacing and lamellar organization, collagen collagen interactions are the major parameter in the regulation of fibril diameter. PMID- 1511727 TI - Variable lymphocyte responses in rats after space flight. AB - Most studies of human blood lymphocyte function following space flight have indicated that microgravity suppresses T cell proliferation. However, several other postflight experiments with animals have shown no decrease in proliferation of lymphocytes from peripheral lymphatic tissues, suggesting that different tissues may be variably affected by microgravity. Therefore, we examined the proliferation of lymphocytes from both spleen and lymph nodes of rats following a 4-day flight aboard the Space Shuttle. The experiments were designed to investigate tissue variability as well as potential mechanisms involved in suppressing proliferation. We found that proliferation of lymph node lymphocytes (LNL) from flight (FLT) animals stimulated with the antigen receptor-dependent T cell mitogen concanavalin A was depressed and could not be restored by supplementing cultures with interleukin 1 or interleukin 2 (IL-2). Response to another receptor-dependent mitogen, phytohemagglutinin, was not decreased. However, proliferation of FLT LNL following stimulation with the receptor independent, mitogenic combination of phorbol ester and ionomycin was depressed. LNL IL-2 activity, cell surface marker expression, and B cell responses to mitogen were normal. Thus, deficits in antigen receptor/ligand interactions, cell surface marker expression, or IL-2 did not account for the suppressed lymphocyte proliferation observed postflight. In contrast to LNL, FLT splenocyte proliferation was not depressed. Assayable IL-2, IL-2 receptor expression, and cell surface marker expression likewise were unaffected by space flight. The differences between lymph node and splenic responses demonstrate the tissue specific nature of microgravity effects on individual lymphatic tissues. PMID- 1511728 TI - The control of polarized integrin topography and the organization of adhesion related cytoskeleton in normal human keratinocytes depend upon number of passages in culture and ionic environment. AB - Keratinocyte adhesion to basal lamina and lateral interactions among basal epidermal cells are mediated, besides other molecules, by integrin receptors that are sorted to defined membrane domains. The hemidesmosome-associated integrin alpha 6 beta 4 is sharply localized to the basal surface of basal cells while alpha 2 beta 1 and alpha 3 beta 1 are enriched laterally. This integrin sorting pattern is perfectly reproducible in vitro by cultured keratinocytes and takes place progressively in primary or secondary culture in the presence of 1.8 mM Ca2+. The polarized topography of integrins is gradually lost with higher passage numbers and between passage 5 and passage 7 there is a complete pericellular redistribution of the above integrins. Along with the decreased basal adhesive value of alpha 6 beta 4 there is a marked increase in the number of focal contacts in high-passage keratinocyte colonies. A similar loss of polarized topography of integrins occurs under low-Ca2+ culture conditions. Increasing the number of culture passages beyond the fifth induces the appearance of the fibronectin receptor alpha 5 beta 1 on the surface of keratinocytes, particularly at intercellular junctions and in some focal contacts. The receptor alpha 5 beta 1 is not detectably exposed by low-passage cells. We propose that forcing keratinocytes into more frequent cell cycles by continuous passaging may perturb the polarized topography of integrins and the adhesion mechanisms of keratinocytes. Then, low-passage keratinocytes are, in our opinion, the most reliable in vitro models for studying the physiology of epidermal cells. PMID- 1511729 TI - Effects of acrylamide on germinal vesicle migration and dissolution in oocytes of the frog, Rana pipiens. AB - We have demonstrated that when Rana oocytes are treated with 10 mM acrylamide, germinal vesicle migration (GVM) is promoted while meiosis reinitiation by progesterone is inhibited. A number of other specific alterations result from the acrylamide treatment: (i) A dense band of fibrillar material appears adjacent to the oolemma in acrylamide-treated oocytes. Furthermore, (ii) the fibrillar material reacts with an intermediate filament antibody using immunogold techniques applied to transmission electron microscopy. Moreover, (iii) acrylamide inhibits progestogen-induced annulate lamellae breakdown. In addition, (iv) the cortical mitochondria-rich layer appears to be thickened by acrylamide, which also (v) affects oocyte microvillar retraction and organization. Finally, (vi) electrophysiological measurement of membrane voltage indicates that acrylamide does not significantly affect cell viability during the incubation period used in this study. In summary, acrylamide exerts profound effects on the physiological event of GVM, and these are consistent with the hypothesis that changes in the cytoskeleton are a contributing factor in meiosis reinitiation. PMID- 1511730 TI - An altered repertoire of fos/jun (AP-1) at the onset of replicative senescence. AB - With multiple divisions in culture, normal diploid cells suffer a loss of growth potential that leads to replicative senescence and a finite replicative capacity. Using quantitative RT-PCR, we have monitored mRNA expression levels of c-fos, c jun, JunB, c-myc, p53, H-ras, and histone H4 during the replicative senescence of human fibroblasts. The earliest and the largest changes in gene expression occurred in c-fos and junB at mid-senescence prior to the first slowing in cell growth rates. The basal level of c-fos mRNA decreased to one-ninth that of the early-passage levels, while junB declined to one-third and c-jun expression remained constant. The decline in the basal c-fos mRNA level in mid-senescence should lead to an increase in Jun/Jun AP-1 homodimers at the expense of Fos/Jun heterodimers and may trigger a cascade of further changes in c-myc, p53, and H ras expression in late-passage senescent fibroblasts. PMID- 1511731 TI - A nuclear protein associated with lethal heat shock of HL-60 cells. AB - The responses to stress in living cells are well known. Thermal stress causes decreased protein synthesis as well as rapid induction of heat shock proteins (hsps), or alternately termed stress proteins (sps). The exposure of cultured promyelocytic leukemia cells (HL-60) to a 45 degrees C lethal heat shock for 1 h elicited synthesis and phosphorylation of a polypeptide M(r) 48,000 and pI 7.5 (p 48) as visualized by two-dimensional polyacrylamide gel ultra microelectrophoresis. p 48, which was not observed at sublethal temperatures (39 and 41 degrees C), was synthesized during all phases of the cell cycle but was phosphorylated only in G0 + G1 and S-phases. The appearance of p 48 was marked by a concomitant and reciprocal reduction in hsps or sps 70 and 90. Distinct protease V8 fragment maps of p 48, hsps 70 and 90 in conjunction with immunochemical determination indicated vast differences in their primary structures. These facts suggest that p 48 was not formed from coalesced breakdown products of hsps 70 or 90. Western blotting showed that p 48 possessed the same immunochemical determinants as two other proteins with the same molecular mass but different isoelectric points. In an association assay, p 48 was shown to bind with actins and hsp 90 from HL-60 nuclei. PMID- 1511732 TI - Retinoic acid- and staurosporine-induced bidirectional differentiation of human neuroblastoma cell lines. AB - The differentiation pattern of two related human neuroblastoma cell lines, SK-N SHF and SK-N-SHN, induced by retinoic acid and staurosporine was studied. Immunohistochemical and electron microscopic examination of the cells indicated that the SHF variant could undergo differentiation along a melanocytic route when treated with retinoic acid and to neuronal cells when treated with retionic acid and staurosporine together. Treatment of SHN cells with either or both these agents caused neuronal differentiation. The melanocytic pathway was characterized in part by the flattening of the cells, the appearance of melanocytic antigens and various forms of melanosomes, an increase in tyrosinase activity, and the absence of neuronal marker proteins. The neuronal route was typified by the development of long neuritic processes containing microtubules and numerous neurosecretory granules as well as by immunohistochemical reactions for neural cell adhesion molecule, synaptophysin, and neurofilament proteins. The significance of these results is discussed in terms of the differentiation responses of neuroblastoma cells to chemical agents as well as some of the factors involved in the regulation of phenotype expressions of these cells. PMID- 1511733 TI - Reversible desensitization of fibroblasts to cadmium receptor stimuli: evidence that growth in high zinc represses a xenobiotic receptor. AB - The xenobiotic Cd2+ triggers the production of inositol trisphosphate and releases stored Ca2+ in certain cell types, apparently by binding to a zinc site in the external domain of an "orphan" receptor (no known endogenous stimulus). Cd2+ and bradykinin evoke similar spikes in cytosolic free Ca2+. Growth in high Zn2+ (100-200 microM) abolished the free Ca2+ spike evoked by Cd2+ without affecting the spike produced by bradykinin. Growth in high Zn2+ almost abolished Cd(2+)-evoked production of [3H]inositol mono-, bis-, and trisphosphate. Bradykinin-evoked [3H]inositol phosphate production was not affected by growth in high Zn2+. Growth in high Zn2+ nearly prevented the stimulation of 45Ca2+ efflux by Cd2+ without affecting the stimulation of 45Ca2+ efflux by bradykinin or histamine. Removing Zn2+ from the culture medium and incubating the cells for several hours fully restored responsiveness to Cd2+. Cycloheximide, actinomycin D, or tunicamycin prevented the restoration of Cd2+ responsiveness, indicating that resensitization requires macromolecular synthesis. Growth in high Zn2+ reversibly abolished Ca2+ mobilization evoked by two additional stimuli: a decrease in extracellular pH or Na+ concentration. These findings support the hypothesis that the three stimuli (Cd2+ or a decrease in external pH or Na+ concentration) activate the same orphan receptor. Growth in high Zn2+ apparently desensitizes the cells to the Cd2+ receptor stimuli by repressing receptor synthesis. PMID- 1511734 TI - Ets-1 and Ets-2 protooncogene expression in theca cells of the adult mouse ovary. AB - We have investigated the mRNA expression of the Ets-1 and Ets-2 genes in murine gonads and found expression in adult ovaries. In situ hybridization experiments show that the Ets genes are predominantly expressed in theca cells and cells of ovarian interstitium. By gel retardation experiments we detected DNA binding proteins in ovaries that specifically bind to the ETS motif, suggesting the expression of Ets or Ets-related proteins. Our results raise the possibility of Ets-2 involvement in ovarian pathology seen in patients with Down's syndrome. PMID- 1511735 TI - Localization of the nuclear matrix protein mitotin in mouse cells with a mitotic or endomitotic cell cycle. AB - Immunofluorescence staining was used to study the precise subcellular distribution of the nuclear matrix antigen, mitotin, in mouse cells characterized by either a mitotic or an endomitotic organization of the cell cycle. In mitotically dividing cells, mitotin showed a speckled distribution within interphase nuclei. In addition, some interphase cells exhibited a weak, focused signal adjacent to the nucleus, reflecting a possible staining of the centrosome region. Using digital contrast-enhanced immunofluorescence microscopy, a distinct association of mitotin to the centrosome, pole microtubules, and midbody could be revealed in cells at different stages of mitosis. In parallel, trophoblast giant cells characterized by an endomitotic cell cycle were derived from blastocyst outgrowths and analyzed likewise. In all giant cells examined so far, mitotin was restricted to the nuclear compartment alone, although different patterns of intranuclear staining could be detected. The present study provides further information about the precise localization of mitotin in mitotic cells, especially during mitosis. In view of the results, the staining pattern observed in endomitotic cells may allow for a better understanding of the origin and the organization of the endomitotic cell cycle. PMID- 1511736 TI - Induced cell surface expression of functional alpha 2 beta 1 integrin during megakaryocytic differentiation of K562 leukemic cells. AB - The pluripotential hematopoietic cell line K562 was studied as a model of inducible integrin expression accompanying differentiation. Differentiation along the megakaryocytic pathway was induced with phorbol 12,13-dibutyrate and differentiation along the erythroid pathway with hemin. Induction of megakaryocytic differentiation was associated with changes in cell morphology and with increased cell-cell and cell-substrate adhesion and spreading. Erythroid differentiation was not associated with changes in morphology or adhesion. Cell surface expression of the IIb-IIIa and alpha 2 beta 1 integrins increased markedly with phorbol treatment but decreased with hemin treatment. Phorbol treated K562 cells, but not control cells or hemin-treated cells, adhered to collagen substrates in a Mg(2+)-dependent manner which was specifically inhibited by a monoclonal antibody directed against the alpha 2 beta 1 integrin. Northern blot analysis revealed that megakaryocytic differentiation of K562 cells was accompanied by de novo expression of the alpha 2 integrin mRNA with no change in the level of mRNA for the beta 1 subunit. K562 cells provide a model of differentiation-dependent, regulated integrin expression in which expression is up- or down-regulated depending upon the differentiation pathway selected. PMID- 1511737 TI - Platelet-derived growth factor in combination with collagen promotes the migration of human skin fibroblasts into a denuded area of a cell monolayer. AB - Since we have found previously that adult donor skin fibroblasts (TIG-114) migrated more slowly in serum-depleted medium than in medium supplemented with 10% FBS, we tried to identify a factor(s) which promotes fibroblast migration from the edge of a denuded area in a monolayer. In medium supplemented with 10% FBS, the effects of both suramin, a competitor of growth factors at the receptor level, and monensin, an inhibitor of the secretion of extracellular matrix, were examined. Both substances suppressed cell migration, suggesting that growth factors and matrix substances are important for cell migration. Then, we examined the effects of growth factors and extracellular matrix on fibroblast migration in serum-free medium. Platelet-derived growth factor (PDGF), basic fibroblast growth factor, acidic fibroblast growth factor, and transforming growth factor-beta did not stimulate cell migration. Type I collagen, plasma fibronectin, and heparin also did not promote cell migration. However, the combination of PDGF and type I collagen did promote cell migration. Addition of anti-PDGF antibody reduced the stimulatory effect induced by the combination of PDGF and type I collagen. These results suggest that the copresence of growth factors and extracellular matrix regulates fibroblast migration into a denuded area in a monolayer. PMID- 1511738 TI - How is rat liver S-adenosylmethionine synthetase regulated? AB - The in vivo regulation of S-adenosylmethionine synthetase, a key enzyme in methionine metabolism, is so far unknown. The enzyme activity has been shown to be modulated by glutathione and the oxidation state of its sulfhydryl groups. Analysis of the protein sequence has revealed the presence of putative phosphorylation sites. A mixed regulatory mechanism combining phosphorylation and the oxido/reduction of sulfhydryl groups is proposed. The role of glutathione in this mechanism is also discussed. PMID- 1511739 TI - Thrombin-induced human platelet aggregation is inhibited by protein-tyrosine kinase inhibitors, ST638 and genistein. AB - We have investigated the involvement of protein-tyrosine kinases in thrombin induced aggregation of human platelets, using ST638 and genistein which are known inhibitors of protein-tyrosine kinase. Preincubation of platelets with 50 microM of ST638 or 25 micrograms/ml of genistein completely blocked the platelet aggregation induced with 0.05 unit/ml of thrombin. The increase of protein tyrosine phosphorylation bands (135-, 124-, 76-, 64-, and 60-kDa) induced with thrombin was also inhibited by these inhibitors in a dose-dependent manner. These inhibitors also blocked the platelet aggregation and protein-tyrosine phosphorylation induced with thrombin in aspirin-treated platelets. Increase of the intracellular Ca2+ concentration induced by thrombin was also inhibited by higher concentrations of genistein. These results suggest that the protein tyrosine phosphorylation plays a certain role in platelet activation having some relation to the intracellular Ca2+ concentration. PMID- 1511740 TI - The gene structure of tetranectin, a plasminogen binding protein. AB - The gene for human tetranectin was isolated from a genomic library with a mixture of degenerate oligonucleotide probes. The gene is about 12 kbp and contains two intervening sequences. The gene encodes a protein of 202 amino acid residues, with a signal peptide of 21 amino acid residues, followed by the tetranectin sequence of 181 amino acid residues. Northern blot analysis revealed that tetranectin mRNA was present in all eight tissues tested with the highest concentration in lung. Southern blot analysis showed hybridization to two genes. Further investigations are needed to determine whether the genes are allelic or non-allelic. PMID- 1511741 TI - Membrane inserted APP fragments containing the beta A4 sequence of Alzheimer's disease do not aggregate. AB - Previously we have shown that the COOH-terminal fragment (A4CT) of the Alzheimer amyloid protein precursor (APP), which at the NH2-terminus carries the sequence of the amyloid beta A4 protein, forms highly insoluble aggregates [EMBO J. (1988) 7, 949-957]. Here we report that aggregation is prevented if A4CT is expressed in vitro with a signal sequence at the NH2-terminus (SPA4CT) under conditions which allow membrane insertion. Aggregates from SPA4CT are obtained after removal of membranes by chloroform/methanol extraction or heating. PMID- 1511742 TI - The zinc finger motif. Conservation of chemical shifts and correlation with structure. AB - Zinc fingers of the transcription factor IIIA (TFIIIA) type, in which zinc is co ordinated by two cysteine and two histidine ligands (Cys2/His2), contain a length of helix packed against a beta-hairpin. These zinc fingers comprise the widest range of structurally homologous proteins for which 1H chemical shifts are available. A number of key resonances have chemical shifts that are highly sensitive to tertiary structure and are conserved between these peptides. The high conservation of these fingerprint chemical shifts is correlated with the common global fold of Cys2/His2 zinc fingers. These chemical shifts are largely independent of primary structure and should facilitate NMR assignments for future zinc finger proteins, as well as provide a diagnostic signature for the characteristic Cys2/His2 zinc finger fold. PMID- 1511743 TI - Co-transcription of the gastrin and cholecystokinin genes with selective translation of gastrin mRNA in a human gastric carcinoma cell line. AB - So far, no cells have been found to synthesize both of the homologous hormones, cholecystokinin and gastrin. Northern analysis and reverse transcription PCR showed, that the human gastric carcinoma cell line (AGS) expresses both a gastrin mRNA of 0.7 kb and a cholecystokinin transcript of 0.8 kb. A library of sequence specific radioimmunoassays, cleavage with processing-like enzymes and chromatography subsequently revealed that the gastrin mRNA was translated into progastrin that was constitutively secreted into the medium (45 +/- 3 pmol/l). Neither procholecystokinin nor any of its processing products were detectable in cells and media. The results suggest that differentiation into gastrin- or cholecystokinin-producing cells may be regulated at the translational level. The gastric cell line, AGS, provides a model for studies of translational regulation of cell differentiation. PMID- 1511744 TI - Distinct and specific GAP activities in rat pancreas act on the yeast GTP-binding proteins Ypt1 and Sec4. AB - Previous studies have demonstrated that Sec4, a 23.5 kDa guanine nucleotide binding protein of the ras superfamily is required for exocytosis in the budding yeast Saccharomyces cerevisiae. Ypt1, another ras-like 23 kDa guanine nucleotide binding protein in yeast has been found to be involved in ER-Golgi transport. A mammalian homologue of Ypt1 called rab1 has also been identified. Recent studies using purified Sec4 protein have identified a component of yeast lystate that specifically stimulates the hydrolysis of GTP bound to Sec4. In the present study, purified recombinant Sec4 and Ypt1 proteins expressed in E. coli have been used as substrates to determine if GTPase activating proteins (GAPs) directed toward these proteins are present in rat pancreas. Our studies showed that 65% of Sec4-GAP activity was associated with the 150,000 x g pancreatic particulate fraction with approximately 35% being found in the cytosol. On the other hand, more than 95% of Ypt1-GAP activity was found to associate with the particulate fraction. Sec4 and Ypt1 competition assays further demonstrated the specificity of the Sec4 and Ypt1 GAPs. The results from the present study suggest the presence of a distinct GAP in the pancreas that interacts with Sec4, and another that interacts with Ypt1. PMID- 1511745 TI - Steroid 21-hydroxylase is a major autoantigen involved in adult onset autoimmune Addison's disease. AB - An adrenal-specific protein reacting with autoantibodies in the sera of patients with adult onset Addison's disease has been purified from human adrenal glands. The protein, mol.wt. 55K, has the biochemical characteristics of steroid 21 hydroxylase and reacts on Western blots with rabbit antibodies to recombinant 21 hydroxylase. Absorption of the native human 55K adrenal protein with human adrenal autoantibodies prevented the subsequent reaction of the 55K protein with rabbit antibodies to 21-hydroxylase in Western blot analysis. In addition, human adrenal autoantibodies reacted with recombinant 21-hydroxylase expressed in yeast. These data indicate that the adrenal specific enzyme steroid 21 hydroxylase is a major autoantigen involved in adult onset autoimmune Addison's disease. PMID- 1511747 TI - The amino acid sequence of a 20 kDa bifunctional subtilisin/alpha-amylase inhibitor from bran [correction of brain] of rice (Oryza sativa L.) seeds. AB - A 20 kDa bifunctional inhibitor of the microbial proteinase, subtilisin, and the alpha-amylase from the larvae of the red flour beetle (Tribolium castaneum) was purified from bran of rice seeds by saline extraction, precipitation with ammonium sulphate, ion-exchange chromatography on DEAE-Cellulose and Toyopearl CM 650, and preparative HPLC on Vydac C18. The complete primary structure was determined by automatic degradation of the intact, reduced and S-alkylated protein, and by manual DABITC/PITC micro-sequencing of peptides obtained from the protein following separate enzymic digestions with trypsin, pepsin, chymotrypsin, elastase and the protease from S. aureus V8. The protein sequence, which contained 176 residues, showed strong homology with similar bifunctional inhibitors previously isolated from wheat and barley which are related to the Kunitz family of proteinase inhibitors from legume seeds. PMID- 1511746 TI - Crystal structure of human recombinant interleukin-4 at 2.25 A resolution. AB - The crystal structure of human recombinant interleukin-4 (IL-4) has been solved by multiple isomorphous replacement, and refined to an R factor of 0.218 at 2.25 A resolution. The molecule is a left-handed four-helix bundle with a short stretch of beta sheet. The structure bears close resemblance to other cytokines such as granulocyte-macrophage colony stimulating factor (GM-CSF). Although no sequence similarity of IL-4 to GM-CSF and other related cytokines has been previously postulated, structure-based alignment of IL-4 and GM-CSF revealed that the core of the molecules, including large parts of all four helices and extending over half of the molecule, has 30% sequence identity. This may have identified regions which are not only important to maintain structure, but could also play a role in receptor binding. PMID- 1511748 TI - Detection of the photoactive protochlorophyllide-protein complex in the light during the greening of barley. AB - A photoactive protochlorophyllide-protein complex with absorbance and fluorescence maxima at 648 and 653 nm was detected in greening barley leaves without any re-darkening. The variations of the amplitudes of the absorbance and the fluorescence of the photoactive protochlorophyllide with greening time at two different light intensities indicate a close relationship between the rate of chlorophyll synthesis and the amount of the complex during the first hours. The chlorophyllide resulting from photoreduction during greening has an absorbance maximum at 684 nm, which shifts towards a shorter wavelength within a few seconds, indicating rapid liberation of the pigment from the enzyme. We conclude that chlorophyll accumulation proceeds through continuous regeneration and phototransformation of the photoactive complex. PMID- 1511749 TI - Inhibitory effect of human chorionic gonadotropin (hCG) on HIV-1 transmission from lymphocytes to trophoblasts. AB - It has been demonstrated that human chorionic gonadotropin (hCG) inhibits HIV production in vitro, suggesting that this soluble placental glycoprotein can control viral replication and spread in vivo. hCG--the major product of fetal trophoblasts--was tested on an in vitro model consisting of choriocarcinoma derived ENAMI trophoblasts exposed to HIV-infected MOLT-4 lymphocytes. The results show a U-shaped antiviral dose-effect and suggest that hCG may contribute to protection against intrauterine transmission of HIV-1. PMID- 1511751 TI - Reduced puromycin sensitivity of translocated polysomes after the addition of elongation factor 2 and non-hydrolysable GTP analogues. AB - Treatment of reticulocyte polysomes with elongation factor eEF-2 and GTP led to an increased sensitivity of peptidyl-tRNA for puromycin as a result of the translocation from the ribosomal A-site to the P-site. Upon addition of an excess of the non-hydrolysable GTP analogue, GuoPP[CH2]P, the puromycin sensitivity decreased rapidly. The decrease in sensitivity required high concentrations of eEF-2 with half maximal effect at an eEF-2 concentration of around 1 microM. The data suggest either that peptidyl-tRNA had re-translocated back to the A-site due to the higher affinity of eEF-2 for the pre-translocation than for the post translocation ribosome, or that the eEF-2-GuoPP[CH2]P complex blocks the peptidyl transferase activity. PMID- 1511750 TI - The His-probe method: effects of histidine residues introduced into the complementarity-determining regions of antibodies on antigen-antibody interactions at different pH values. AB - We examined the effects of histidine residues that were artificially introduced into complementarity-determining regions of antibodies on antigen-antibody interactions at different pH values. Using a monoclonal antibody specific for hen egg-white lysozyme and three mutant antibodies that contained a histidine residue, we measured binding constants for antibodies and lysozyme at different pH values (pH 5-8). No gross conformational changes were evident over this range of pH values, as determined by analysis of the spectra of circular dichroism. Since the charge on a histidine residue is the most likely factor that can vary over this range of pH values, differences on pH-dependent antigen-binding patterns observed between the wild-type and mutant antibodies should be due mainly to the effects of the charges on the histidine residues. The three mutant antibodies showed different and characteristic patterns of pH-dependent binding to lysozyme, which depended on the location of the artificially introduced histidine residues. PMID- 1511753 TI - [Should screening for type I diabetes in children of insulin dependent parents be encouraged?]. PMID- 1511752 TI - [Discovery of pancreatic diabetes in Strasbourg]. AB - Although many clinical aspects of diabetes were already known in the second half of the XIXth century, its pathogenesis remained mysterious. The German Medical School of Strasbourg, rich of numerous eminent teachers and researchers such as A. Kussmaul and B. Naunyn in the 1880ies, represented by this time one of the leading centers in diabetes research. The studies of Joseph Freiherr Von Mering on phloridzin-induced glycosuria are an example between others, but the discovery by Oskar Minkowski of the pancreatic origin of the disease undoubtedly stands as the most famous. This discovery was partly indebted to luck since Von Mering and Minkowski were studying a problem of digestive absorption of lipids, but it was greatly due to the excellent clinical and experimental training of Minkowski, as well as his operatory skill. These works, initially criticized by some authors, turned out to stimulate in several countries researchs on the isolation from pancreas of an hypoglycemic substance. Several investigators gave up or failed near the end, which was reached in 1921 by F. Banting and C. Best, subsequently opening the therapeutic era of diabetology. PMID- 1511754 TI - [Introduction to molecular biology. Vocabulary and basic concepts]. PMID- 1511755 TI - Effect of oral contraceptive use on the incidence of impaired glucose tolerance and diabetes mellitus. AB - Combined estrogen-progestin high-dose oral contraceptives increase the risk of impaired glucose tolerance which is estimated at approximately 12% of oral contraceptive current users. Glucose tolerance is adversely affected by the chemical structure of the progestins contained in oral contraceptives such as estrane (norethindrone, ethynodiol) and particularly gonane (norgestrel). The women at high risk to develop an impaired glucose tolerance on high-dose, oral contraceptives are those with previous gestational diabetes, with a positive family history of diabetes mellitus in a first-degree relative, or who are obese or older. Low-dose oral contraceptives with a reduced content of estrogen and progestogen such as levonorgestrel or desogestrel as well as the triphasic oral contraceptives containing a low daily dose of levonorgestrel or gestodene, are associated with a significantly lower risk of impaired glucose tolerance, even in women with previous gestational diabetes. Noteworthy however is the ability of low-dose progestogen containing oral contraceptives, such as low dose gonane or estrane oral contraceptives, to induce glucose intolerance by increasing the plasma insulin response to oral glucose. Impaired glucose tolerance is often reversible within 6 months of discontinuing oral contraceptives, except for oral contraceptive users with previous gestational diabetes. Development of diabetes mellitus in high-dose oral contraceptive users is rare. PMID- 1511756 TI - Effect of 50 and 100 g glucose loads on peripheral muscle glucose metabolism in normal man. AB - The present study was designed to determine the effects of 50 and 100 g glucose loads on forearm muscle glucose uptake, oxidation and nonoxidative glucose metabolism in normal man. Ten healthy male subjects were studied during the postabsorptive state (12-14 h overnight fast) and for 3 hours following glucose ingestion. Peripheral glucose metabolism was analysed by the use of the forearm technique to estimate muscle exchange of substrate combined with indirect calorimetry. Greater forearm muscle uptake and nonoxidative metabolism of glucose were observed in the subjects during the G.100 study than during the G.50 study (G.100 = 178.9 +/- 19.7 and 155.3 +/- 23.0 vs 103.5 +/- 16.6 and 85.2 +/- 16.7 mg/100 g forearm muscle. 3 h, respectively). the muscle glucose oxidation did not show significant difference after the two glucose loads. Insulin levels reached after 100 g glucose ingestion were significantly higher than after the 50 g glucose load. In conclusion, this study revealed a dose-dependent metabolic response in the muscular tissue of normal subjects to oral glucose loads of 50 and 100 g, with respect to forearm muscle glucose uptake and nonoxidative glucose metabolism. The oxidative responses of the muscle tissue to the oral glucose challenges seem not to be directly proportional to the ingested meals. PMID- 1511757 TI - Interaction of lipid and carbohydrate metabolism after infusions of lipids or of lipid lowering agents: lack of a direct relationship between free fatty acid concentrations and glucose disposal. AB - The present work was planned to study the effects of changes in lipid metabolism irrespective of FFA concentrations (FFA) on the regulation of oxidative and nonoxidative disposal of a glucose infusion during hyperinsulinaemia. Fifteen normal volunteers participated in the 3 protocols, in which 1) Intralipid 2) beta pyridylcarbinol or 3) isotonic saline were infused during 2 hours. Thereafter, these infusions were discontinued and a two-hour euglycaemic hyperinsulinaemic clamp was performed. All three studies were carried out in combination with indirect calorimetry to measure glucose uptake, and oxidative and nonoxidative glucose disposal (corresponding essentially to glucose storage). Plasma FFA concentrations were 508 +/- 34, 601 +/- 43 and 546 +/- 45 mumol/l in the basal state during the Intralipid, beta-pyridylcarbinol and control protocols. It increased to 960 +/- 71 mumol/l after the Intralipid infusion, fell to 246 +/- 17 mumol/l after the beta-pyridylcarbinol infusion, vs 600 +/- 48 mumol/l in the control. At the end of the glucose-insulin clamp the values were low in the 3 protocols: 263 +/- 17, 233 +/- 19 and 204 +/- 14 mumol/l. Intralipid infusion prior to the clamp protocol induced a suppression of both insulin-mediated glucose uptake (4.91 +/- 0.46 (Intralipid) vs 6.83 +/- 0.63 mg.kg-1.min-1 (saline)) and storage (1.61 +/- 0.34 vs 2.99 +/- 0.53 mg.kg-1.min-1) while beta pyridylcarbinol infusion induced an increased insulin-mediated glucose uptake (8.58 +/- 0.37 mg.kg-1.min-1) and in glucose storage (4.29 +/- 0.31 mg.kg-1.min 1) (p less than 0.5 vs Intralipid). These changes occurred even though FFA plasma concentrations were similar in the 3 experimental conditions.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1511758 TI - Spontaneous diabetes in bio-breeding rats: evidence for insulin dependent liver microsomal delta 9 stearic acid desaturation. AB - We studied liver microsomal delta 9 stearic acid desaturase activity and fatty acid composition of liver phospholipids and microsomal total lipids in the insulin-dependent spontaneously diabetic adult male Bio-Breeding rat. The diabetic Bio-Breeding rats (3 weeks of diabetes) were killed 48, 17 and 3 h after the last insulin injection (1.0 IU, 100 g body weight-1 day-1). Under these experimental conditions, delta 9 desaturase activity was defective during the normo- and hyper-glycaemic periods and restored during the hypoglycaemic period which followed the insulin injection to the diabetic rats. The fatty acid composition of diabetic rat liver phospholipids and microsomal total lipids were not consistent with delta 9 desaturase activity at the different periods of glycaemia and may be explained by factors other than disturbances of this desaturation. PMID- 1511759 TI - Sulfate metabolism in experimental diabetes. AB - Previous studies have indicated altered rates of sulfate clearance in experimental diabetes, but have disagreed on the magnitude and direction of change of serum sulfate, or its impact on tissue sulfate concentrations. The present study was undertaken in order to investigate the temporal effects of streptozotocin-induced diabetes on sulfate pools in the rat. In contrast to some earlier reports, we found no effects of diabetes on serum sulfate concentrations throughout 12 weeks of disease, as measured by ion chromatography. However, marked increases in sulfate concentration were found in liver cytosol (3.5-fold; p less than 0.0005) and kidney (1.7-fold; p = 0.002) by 7 weeks. The measurement of inulin space demonstrated that the changes in hepatic sulfate were due to increased concentrations of the ion in the cell cytosol. Normal serum sulfate concentrations, together with reports of increased renal clearance of sulfate in diabetes, suggest an intracellular origin of the excess cytosolic sulfate. Glucose did not affect the uptake of sulfate by renal mesangial cells in culture. These aberrations in sulfate metabolism are not such as to compromise biological sulfation reactions, and cannot account for reported changes in the incorporation of sulfate into basement membrane proteoglycans during diabetes. PMID- 1511761 TI - Medical complications in pregnancy and delivery of gifted children. AB - A questionnaire on medical complications in pregnancy, labor and delivery was given to 195 families of gifted children. 156 (80%) answered the questionnaire. The incidence of medical disorders in this group did not differ from the accepted incidence in a normal obstetric population. There was a sex ratio of 71.5% boys and 28.5% girls, and a higher probability of another gifted child in these families. PMID- 1511760 TI - Vitamin B12 among parturients and their newborns and its relationship with birthweight. AB - Vitamin B12 (Cobalamin) is an essential nutrient in the diet of humans, particularly during pregnancy, nevertheless very few epidemiological studies have been reported, particularly concerning variation factors. The purpose of this study is to assess the role of vitamin B12 on birthweight after taking into account potential confounders, such as obstetrical, socioeconomic, and biological factors which will be identified. This study was conducted on 188 single births occurring during a 5-month period in an obstetrical care unit in Paris. Vitamin B12 plasma levels and folate plasma levels of mothers and cords along with haematological parameters were measured. Social and obstetrical features of the mothers as well as their tobacco exposure and alcohol consumption were recorded. Cord blood vitamin B12 levels were highly correlated with maternal levels (r = 0.63, P less than 0.001) and were 2-3-fold higher. Three variation factors of vitamin B12 were identified: maternal age, ethnicity and tobacco exposure. Negative correlations between birthweight and vitamin B12 levels were observed only among the smoker group (r mothers = -0.46, P less than 0.05 and r cords = 0.42, P less than 0.05). After adjustment for ethnicity and parity, birthweight remained negatively linked to vitamin B12 in smokers. This relationship could suggest that the availability of vitamin B12 for fetal development depends on certain biological factors present only in mothers who smoked. We hypothesized this relationship could be explained, in part, by lipid metabolism, particular to smokers. PMID- 1511762 TI - Comparison between metal cup and silicone rubber cup vacuum extractor. AB - A total of 400 primiparous patients who were delivered by vacuum extractor were studied. The patients were divided in two groups: Group A included 200 patients who were delivered by metal cup vacuum extractor and Group B consisted of 200 patients who were delivered by rubber cup vacuum extractor. There were no statistically significant differences in the mean maternal age, mean gestational age, mean neonatal birth weight, indications for operative delivery, occipital positions and head stations between the two groups. No differences were found in the rates of birth canal trauma (11% vs. 12.5%), major neonatal scalp trauma (6.5% vs. 5.5%), neonatal jaundice (15.5% vs. 13.5%) and Apgar score. From this study we can conclude that both metal and silicone cups are equally satisfactory for vacuum extraction. PMID- 1511763 TI - Quantitation of breathing-related modulation of umbilical arterial and venous flow velocity waveforms in the normal term fetus. AB - The effect of fetal breathing activity on umbilical arterial and venous flow velocity waveforms was studied in 11 normal pregnant subjects at term during fetal behavioural state 2F (Nijhuis et al. Early Hum Dev 1982;6:177-195). A total of 1041 breathing cycles was evaluated. Our data suggest a net reduction in venous flow velocity during fetal breathing activity. In contrast to venous flow velocity, the magnitude of breathing-related modulation of arterial pulsatility is small and independent of breathing amplitude. Nevertheless, for clinical purposes umbilical arterial flow velocity waveform recording during fetal apnea is recommended. PMID- 1511764 TI - Abnormal fetal behaviour in first trimester spontaneous abortion. AB - The behaviour of 5 fetuses at 10 weeks of gestational age that later underwent a spontaneous abortion during the first trimester of pregnancy was compared to similar aged normal fetuses (n = 116). Marked abnormalities of behaviour were noted in three of the pregnancies that spontaneously aborted. These behavioural abnormalities were not identified in any of the pregnancies which continued to term. We conclude that fetal behaviour, which reflects the neural integrity of the individual, and thus fetal well-being, can be used during the first trimester to give an indication as to the viability of the on-going pregnancy. PMID- 1511765 TI - Routine previous cesarean scar exploration following successful vaginal delivery. Is it necessary? AB - Among the 960 women who successfully delivered by vaginal route after previous cesarean section, 10 (1.04%) had complete lower segment scar rupture over a 9 year period. All were sufficiently symptomatic in order to suspect a ruptured uterus prior to scar exploration. We conclude that lower uterine segment palpation should be reserved only for symptomatic patients. PMID- 1511766 TI - Severe ovarian hyperstimulation: a case report and essentials of prevention and management. AB - A case of ovarian hyperstimulation syndrome is presented occurring in a young woman with polycystic ovary-like disease after induction of ovulation with the combined treatment of a luteinizing hormone releasing hormone analog and human menopausal gonadotrophins. Prevention and management based on pathophysiological considerations are reviewed. PMID- 1511767 TI - Determinants of hormonal replacement therapy in recently postmenopausal women. AB - Although the efficacy of hormonal replacement therapy (HRT) on the consequences of the menopause is not questioned, it appears that in Europe and in the USA only a small proportion of women are users of HRT. In this study, we examined the prevalence and the determinants of HRT among 1986 French menopausal women, aged 45 to 55 years, presenting to a preventive medicine centre. Overall, 8.1% of women reported current use of HRT. The estrogen preparation most commonly reported was transcutaneous 17 beta-oestradiol. The first determinant of current HRT was birth-place. Women born in France were nearly four times more likely to be on treatment than foreign-born women. A surgical menopause multiplied the probability of current HRT by 2, as did a high level of education. An age at first pregnancy of more than 20 and less than 4 children were also positively linked with HRT use. Even in this population of recently menopausal women, volunteering to undergo health evaluation, the prevalence of HRT was low. The reservations towards HRT may be partly due to the women themselves, and partly due to the physicians. It seems very important to inform the medical profession about the risks and benefits of HRT, and to understand more precisely the reasons why so few women use HRT. PMID- 1511768 TI - First steps in the development of an information and counselling service for women with an abnormal smear result. AB - A study was conducted to develop and evaluate an information leaflet and to investigate the acceptability of a counselling service for women with an abnormal smear result. A newly constructed information leaflet which addressed concerns related to receipt of an abnormal smear result and its medical management was compared for ease of readability with five other leaflets in current use and found to be superior. 144 women were given the leaflet either prior to a colposcopy examination or outpatient ablative treatment and randomly assigned to two recruitment strategies to examine the acceptability of a counselling interview. There was no significant difference between the two strategies and an uptake rate of 80% suggested that women welcomed such an opportunity. An interview evaluation schedule yielded a 98% positive response rate which indicated that the women were satisfied with the counsellor and found the interview useful. Significant differences emerged before and after medical intervention. Patients reported less anxiety, improved mood, and less distress related to the smear result and subsequent medical procedures immediately after the medical interventions (P less than 0.001). PMID- 1511769 TI - Pregnancy and protein C deficiency. AB - This report examines a patient with recurrent attacks of thrombo-embolism due to a protein C deficiency. Alterations in the coagulation during pregnancy and the possible consequences of an altered coagulation during pregnancy will be discussed. PMID- 1511770 TI - Prenatal ultrasound diagnosis of an intracranial teratoma influencing management: case report and review of the literature. AB - Of seventeen cases of prenatally diagnosed intracranial teratomas, fourteen babies were delivered through a cesarean section. All children died before or shortly after delivery. In this report another case is presented of ultrasound diagnosis of an intracranial teratoma. The teratoma filled the whole fetal cranium, and eroded through the skull base into the left maxillary region. In full agreement with the wishes of the parents, conservative management resulted in the spontaneous vaginal delivery of a fetus that died during labor as a result of brain compression and acidosis during the second stage. In contrast with other cases in the literature, no encephalocentesis was performed. In order to minimize maternal morbidity, it is advised to induce or accept labor as soon as the diagnosis is clear and to pursue a vaginal delivery. PMID- 1511771 TI - Serum concentrations of magnesium and parathyroid hormone in randomly selected hospital in-patients and out-patients, and in in-patients with dementia. AB - The relationship between hypomagnesaemia and the secretion of parathyroid hormone was studied. Serum parathyroid hormone (PTH) concentrations were measured in 63 randomly selected patients and 54 hospitalized demented patients using carboxyl terminal PTH53-84 (h-PTH53-84), mid-region PTH44-68 (m-PTH44-68) and intact PTH1 84 kits. Both groups of patients were further subdivided into those with near normal serum magnesium concentrations (1.7 - 3.2 mEq/l) and those with hypomagnesaemia (1.2 - 1.6 mEq/l). Serum h-PTH53-84, m-PTH44-68 and PTH1-84 concentrations in both the randomly selected and the demented patients with hypomagnesaemia were significantly lower than those in the groups with near normal serum magnesium concentrations. The results suggest that parathyroid hormone secretion was inhibited in randomly selected patients and dementia patients with hypomagnesaemia. PMID- 1511772 TI - Caffeine reduces the hepatotoxicity of paracetamol in mice. AB - Paracetamol causes extensive liver damage when taken in overdose quantities; however, it is less hepatotoxic when administered in combination with caffeine. The present work in mice was undertaken to study the effect of caffeine on mortality rates and biochemical and histological parameters of liver damage after administration of toxic doses of paracetamol. It was found that caffeine markedly increased the survival rate after administration of a dose of paracetamol that was lethal to 50% and 100% of mice, reduced liver damage as assessed by serum glutamic pyruvic and glutamic oxaloacetic transaminase activities, partially prevented the depletion of reduced glutathione and reduced histological changes to the liver accompanying paracetamol intoxication. The results support the possibility that caffeine might be useful for the treatment of paracetamol intoxication in humans. PMID- 1511773 TI - Inhibitory effect of nafamostat mesilate on metastasis into the livers of mice and on invasion of the extracellular matrix by cancer cells. AB - Although many agents that interfere with clotting mechanisms have been investigated for their potential to inhibit metastasis, their toxicity has prevented administration of sufficiently high doses to achieve inhibition of metastasis in clinical trials. Nafamostat mesilate (FUT-175), a synthetic serine protease inhibitor, inhibited liver metastasis in a CDF1 mice model with colon 26 adenocarcinoma cells. The apparently dose-dependent inhibitory effect was seen 21 days after all of the doses tested (0.3, 1.0, 3.0 and 10.0 mg/kg for 7 days) but the effect was only statistically significant (P less than 0.01) at the highest dose. The blood concentrations 3 min after dosing were less than 10(-6) M for all of the doses tested. At a concentration of 10(-5) M or less nafamostat mesilate was not cytotoxic towards colon 26 cells in vitro. The results indicate that it may not be difficult to achieve blood nafamostat mesilate concentrations that inhibit metastasis in mouse liver. Possible mechanisms of nafamostat mesilate are inhibition of extravasation and invasion of cancer cells, inactivation of collagenase due to inhibition of plasmin activity and inhibition of the formation of the cancer cell thrombus, and arrest in the capillaries through inhibition of thrombin activity. These preliminary results suggest that peri-operative administration of nafamostat mesilate may prevent metastasis into the liver after surgery for gastrointestinal malignancies. PMID- 1511774 TI - Effects of sodium hyaluronate on tympanic membrane perforations. AB - The effects of topically applied 1% sodium hyaluronate as an alternative treatment to surgery for tympanic membrane perforations was studied. In an open study, the inclusion criteria were increased by accepting patients previously treated by surgery or with placebo and, compared with a previous study, the frequency at which sodium hyaluronate was applied was reduced. Reduction in the size of the perforation was detected in 12/16 (75.0%) patients, six (37.5%) of whom showed complete tympanic healing, and in the remaining four (25.0%) there was no healing. The average percentage reduction in the perforation area was 80.5%. The two factors altered in this trial, i.e. inclusion criteria and frequency of administration of treatment, had little influence on the degree of membrane healing. PMID- 1511775 TI - Estrogen negatively regulates rat gonadotropin releasing hormone (rGnRH) promoter activity in transfected placental cells. AB - To dissect the functional architecture of the rat gonadotropin releasing hormone (GnRH) gene promoter and its regulation by estrogen, gene transfer studies were performed in a placental cell line. 5'-Deletional constructs demonstrated that cis-acting elements important for rGnRH promoter activity in placenta were contained within a region of the proximal promoter between -73 and -16 bp upstream of the transcription initiation site. In addition, an inhibitory region was found from -903 to -424. Deletion of sequences to -424 which removed the inhibitory region, produced a promoter fragment which exhibited a 50% inhibition of GnRH promoter activity in the presence of estrogen (E) and cotransfected estrogen receptor. Negative regulation by E was retained in constructs deleted to -73 bp. We conclude that sequences important for placental cell expression and estrogen regulation of rGnRH lie within the region from -73 to -16. In addition, potential repressor sequences active in placental cells are present between -903 to 424. PMID- 1511776 TI - Transfected insulin-like growth factor II modulates the mitogenic response of rat thyrocytes in culture. AB - Rat thyroid cells (FRTL5), transfected with the sequence coding for rat insulin like growth factor II (IGF-II) presented mRNA specific for the transfected IGF-II in most of the clones obtained (Tr clones). Tr7 and Tr12 cells maintained their ability to respond to the mitogenic effect of thyrotropin (TSH), while either exogenous IGF-I or IGF-II or insulin failed to stimulate their proliferation. In the absence of exogenous mitogens the Tr7 and Tr12 clones vigorously incorporated [3H]thymidine into DNA. This activity was significantly inhibited by sm1.2, a monoclonal antibody against rat IGF-II. Tr7 and Tr12 clones possess type I IGF receptors, known to mediate the mitogenic effect of IGF-II, with affinity similar to those present on the membrane of the parental cells but with reduced capacity. Finally, media conditioned by Tr7 and Tr12 increase basal thymidine incorporation in quiescent FRTL5 cells and amplify that induced by TSH. Endogenous IGFs may play an important role in the regulation of thyroid cell proliferation by modulating the mitogenic effect of TSH and by supporting TSH-independent growth. PMID- 1511777 TI - Androgens increase insulin receptor mRNA levels, insulin binding, and insulin responsiveness in HEp-2 larynx carcinoma cells. AB - Androgen receptors have been found in human larynx and androgens have been supposed to play an important role in promoting the growth of laryngeal carcinomas. The molecular mechanism underlaying this phenomenon is not at all understood. Aim of this work was to investigate the effects of two androgens (testosterone and dihydrotestosterone) on insulin receptor mRNA levels and insulin binding activity as well as on either metabolic or growth-promoting actions of insulin in a human larynx carcinoma cell line (HEp-2). We found that HEp-2 cells express a high affinity insulin receptor. Both androgens significantly increase insulin receptor mRNA levels and insulin receptor number in HEp-2 cells. Insulin action, evaluated either as total glucose utilization or as [3H]thymidine incorporation into DNA, significantly increased in HEp-2 treated with androgens in comparison to control cultures. Altogether, our data allow us to speculate that the increased insulin effectiveness we observed in the larynx carcinoma cell line HEp-2 after androgen treatment might be involved in the regulation of larynx cancer cells growth. PMID- 1511778 TI - Calbindin-D9k mRNA is tightly regulated during the estrous cycle in the rat uterus. AB - Calbindin-D9k (CaBP-9k) is a cytosolic calcium binding protein with a molecular weight of 9000. CaBP-9k is mainly expressed in intestine, uterus and placenta, with intestinal levels controlled by vitamin D and uterine levels controlled by estrogens. CaBP-9k mRNA levels were measured in rat uterus throughout the estrous cycle. On the morning of proestrus, estrus and diestrus animals were sacrificed. Serum 17 beta-estradiol concentrations were determined using a radioimmunoassay. Whole uterus was used for preparation of total RNA. Northern blot analysis was performed to quantify CaBP-9k and beta-actin mRNA. CaBP-9k levels were highest at proestrus, dropped 10-fold at estrus and were not detectable at diestrus. beta Actin levels did not change significantly throughout the estrous cycle. Peak 17 beta-estradiol concentrations coincided with maximum CaBP-9k mRNA expression at proestrus. Despite minimal concentrations of 17 beta-estradiol at estrus, CaBP-9k mRNA was still present at 10% of the proestrus level. At diestrus, CaBP-9k mRNA was not detectable despite increasing 17 beta-estradiol. It is concluded that CaBP-9k is subject to 17 beta-estradiol regulation during the estrous cycle. Correlation between CaBP-9k mRNA and 17 beta-estradiol levels indicates a lag period for CaBP-9k induction in diestrus following a rise in steroid hormone levels. PMID- 1511779 TI - Functional expression of an ovine growth hormone receptor in transfected Chinese hamster ovary cells. AB - Structural heterogeneity has been demonstrated for growth hormone (GH) receptors from a number of species, and both high and low affinity art receptors have been characterised by ligand binding studies. In the present study, we have transfected Chinese hamster ovary (CHO-K1) cells with a cDNA clone encoding a full-length transmembrane ovine (o) GH receptor, under the regulatory control of the human metallothionein IIA promoter. A stably transfected cell line was established (GHR9.5) which expresses on the cell surface a single class of receptor which binds 220,000 [125I]oGH molecules at high affinity (Kd = 0.30 nM) which is comparable to the affinity established for endogenous oGH receptors in postnatal sheep liver microsomes (Kd = 0.27 nM, Freemark et al. (1987) Endocrinology 120, 1865-1872). The expressed receptor also binds ovine placental lactogen (oPL, 205,000 binding sites per cell) with high affinity (Kd = 0.76 nM). The presence of two species of oGH receptor was detected in GHR9.5 cells using affinity cross-linking analysis (M(r) 148,000 and M(r) 73,000) and given that the oGH receptor cDNA codes for a non-glycosylated receptor of M(r) 69,914, it is likely that these cross-linked species correspond to homodimeric and monomeric forms of the oGH receptor, each binding to a single molecule of GH. Parallel cross-linking studies with sheep liver microsomes also demonstrated two oGH receptor species (M(r) 133,000 and M(r) 58,000), the difference in relative molecular weights between the transfected and endogenous receptors presumably resulting from tissue-specific post-translational modifications. In the presence of oGH, the GHR9.5 cells respond by increasing total cellular protein synthesis by 27% relative to non-GH-exposed GHR9.5 cells, indicating the functionality of the expressed receptor. We also demonstrate unequivocally that oPL, through a specific interaction with the transfected oGH receptor, is able to mediate a similar cellular response (38% protein synthesis induction). Responsiveness to oGH and oPL in the GHR9.5 cells is dependent on serum starvation prior to oGH exposure and occurs only with prolonged exposure (greater than 2 h) to oGH. This cellular stimulation occurs independently of c-fos transcription which has previously been shown to be one of the earliest events associated with GH action in tissues expressing endogenous GH receptors (Doglio et al. (1989) Proc. Natl. Acad. Sci. USA 86, 1148-1152; Slootweg et al. (1990) J. Mol. Endocrinol. 4, 265 274). PMID- 1511780 TI - Increased ornithine decarboxylase activity in kidneys undergoing hypertrophy in experimental diabetes. AB - Renal hypertrophy and hyperfiltration are early manifestations of human and experimental diabetes that may contribute to the late development of diabetic nephropathy. The biochemical events resulting in kidney growth in the diabetic state are completely unknown. Since growth of various tissues is accompanied by increased formation of polyamines, we studied whether polyamines were involved in the growth of the kidney observed in diabetic rats. This was done by measuring the activity of the rate-limiting enzyme in the polyamine pathway (ornithine decarboxylase; ODC) in kidneys from control, diabetic and insulin-treated diabetic animals. The ODC activity in the kidney was increased in the diabetic animals with a maximal rise 24 h after diabetes induction (6-fold, P less than 0.01); the activity thereafter declined. However, on day 14 the activity was still significantly elevated (2.5-fold, P less than 0.05). In insulin-treated diabetic animals the kidney ODC activity was only increased 3-fold (P less than 0.05) after 24 h, and for the rest of the study period the activity was about 1.8 fold higher than in control rats. After 14 days the kidneys from diabetic rats were significantly larger than kidneys from both control and insulin-treated diabetic rats, 1066 +/- 43 mg vs. 904 +/- 16 mg and 959 +/- 36 mg, respectively (P less than 0.01). For comparison, the ODC activity was also investigated in muscle. However, in muscle from diabetic animals the ODC activity declined steadily during the 14 days to 34% of control values (P less than 0.01), and insulin treatment completely normalized the ODC activity in muscle.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1511781 TI - Noncytoplasmic and filamentous appearance of calbindin-D28k and tubulin in double, indirect immunofluorescent staining of embryonic chick tissue. AB - Double indirect immunofluorescent labeling of embryonic chick tissue was undertaken for the vitamin D-induced calcium binding protein, calbindin-D28k, and microtubules. Immunoreactivities for both calbindin-D28k and tubulin were found to exhibit a filamentous staining pattern in mesonephros, metanephros, intestine, and brain. In the intestine, staining was absent at 19 days, while immunolabeling of tubulin became evident at 20 days, and both antigens were present in 21-day tissue. In intestinal epithelium, as well as in 10-day metanephros, it was strikingly evident that cells either stained for both antigens or were negative for both calbindin-D28k and tubulin. In 11-12-day metanephros, an increased number of cells with both immunoreactivities were found. In 15-17-day brain, tubulin was evident within all cells but stained most intensely in Purkinje cells which were also positive for calbindin-D28k. Mesonephros from 4-5-day embryos revealed immunolabeling of both tubulin and the calcium binding protein. A statistical analysis of the various cell types revealed that the vast majority contained either both antigens or neither of the immunoreactivities. Of the more than 600 cells scored, none were found to be positive for calbindin-D28k, while at the same time negative for tubulin. It is concluded that calbindin-D28k exhibits a noncytoplasmic distribution in all tissues tested and that the filamentous appearance may reflect localization of the antigen in tubulo vesicular organelles associated with cytoskeleton. PMID- 1511782 TI - Signal transduction mechanisms involved in carbachol-induced aldosterone secretion from bovine adrenal glomerulosa cells. AB - In cultured bovine adrenal glomerulosa cells, diacylglycerol content remains elevated for up to 75 min following the removal of angiotensin II. This maintained increase could provide a mechanism by which angiotensin II pretreatment may prime cells to secrete aldosterone in response to the calcium channel agonist Bay K 8644. In the present study we find that carbachol failed both to produce this persistent diacylglycerol elevation and to exert a priming effect. In addition, because carbachol was also a less potent activator of phospholipase D than angiotensin II, our results implicate phospholipase D in the maintained increase in diacylglycerol content observed following stimulation with and removal of angiotensin II. Carbachol also elicited changes in the radiolabeled levels of both myristate- and arachidonate-containing diacylglycerol. However, the rapid decline in diacylglycerol content following carbachol removal resembled the rapid fall in arachidonate-diacylglycerol; we therefore proposed that the diacylglycerol species generated with carbachol stimulation contains predominantly arachidonic acid. In summary, our results suggest that prolonged elevations in diacylglycerol content following removal of hormones such as angiotensin II, as well as the identity of the diacylglycerol species itself, may be important in the regulation of cellular responses. PMID- 1511783 TI - Protein kinase C modulates cell swelling-induced Ca2+ influx and prolactin secretion in GH4C1 cells. AB - In GH4C1 rat pituitary cells, cell swelling stimulates prolactin (PRL) secretion by increasing Ca2+ influx through nifedipine-sensitive Ca2+ channels; however, the mechanism by which cell swelling opens Ca2+ channels is still unclear. To evaluate the role of protein kinase C (PKC) in this phenomenon, we studied the effect of down-regulating PKC by 12-h pretreatment with phorbol ester or by treatment with H-7, a protein kinase C inhibitor. Cell swelling induced by either 27% medium hyposmolarity or 80 mM isotonic urea caused a prompt rise in both [Ca2+]i and PRL secretion in otherwise untreated control GH4C1 cells. Removal of medium Ca2+ enhanced the osmotically induced cell swelling but prevented the increase in [Ca2+]i and PRL secretion. Both PKC down-regulation and H-7 suppressed the cell swelling-induced increases in [Ca2+]i concentration and PRL secretion, although they enhanced the induced cell volume expansion. Our data indicate that in GH4C1 cells PKC plays an important positive modulating role in the osmotic opening of plasmalemma Ca2+ channels, a critical component of the early transduction chain by which cell swelling causes PRL secretion in tumor derived clonal pituitary cells. PMID- 1511784 TI - Adaptive response in beta-cell function in pancreatic islets isolated from partially pancreatectomized rats. AB - Before clinical onset of insulin-dependent diabetes mellitus a decreasing pancreatic beta-cell mass maintains glucose homeostasis. We currently aimed to study the function of pancreatic islets isolated 2 weeks after a 60% partial pancreatectomy (P) or after a sham operation (S) on adult rats. Experiments on the islets were subsequently performed acutely (day 0) and after 1 week (day 7) of tissue culture in medium RPMI 1640 (11.1 mM glucose) + 10% calf serum. There was no difference in the body weight 2 weeks after surgery. The pancreatic remnant weight of the P rats was 35% less than the pancreatic weight in the S rats. The islet DNA content was 25% higher in the islets of the P rats on day 0, indicating a stimulated islet growth. However, this difference did not remain after culture for 7 days. Islet proinsulin mRNA content and (pro)insulin biosynthesis rates were slightly increased in the islets of P rats on day 0, which could be due to the increased islet mass. The islet insulin content was not different on day 0, but was higher after culture in the islets of the P rats. The islet rates of glucose oxidation and insulin release were markedly higher in the P rats on day 0, suggesting a selective effect on these processes. A higher glucose oxidation rate was, however, not evident on day 7. The relative fraction of insulin-positive cells was slightly lowered in the islets of the P rats on day 0.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1511785 TI - Hormonal regulation of the type III isoform of C-kinase in porcine ovarian tissues. AB - C-kinase activity is notably increased in corpora lutea (CL) compared to preovulatory follicles of porcine ovaries. Our purpose was to identify the C kinase isoform(s) involved in this increase and to examine the expression of C kinase in ovarian tissues at different stages. The major component of C-kinase activity in the CL was isoform III, with a molecular weight (M(r)) of 80,000. Minor activities were attributed to the type II isoform (M(r) = 80,000) and an unidentified C-kinase activity (M(r) = 77,000). C-kinase was not partitioned differently in preovulatory follicles and CL as demonstrated by tissue homogenization in the presence of a detergent and increased chelators. A 3-fold increase in immunoreactive C-kinase was detected in postovulatory follicles relative to preovulatory. A second, nearly 3-fold increase in C-kinase was detected in mature CL relative to postovulatory follicles. These increases are examined in the context of the complex hormonal regulation of the porcine CL. PMID- 1511786 TI - Characterization of the gonadotrophin-releasing hormone calcium response in single alpha T3-1 pituitary gonadotroph cells. AB - Intracellular calcium ([Ca2+]i) was measured in single immortalized gonadotroph alpha T3-1 cells using dual wavelength fluorescence microscopy combined with dynamic video imaging. Gonadotrophin-releasing hormone (GnRH, 10(-8) M) produced a biphasic rise in [Ca2+]i which could be abolished by a GnRH antagonist. The initial calcium transient was complete within seconds while the smaller secondary plateau phase lasted several minutes. The calcium spike was reduced by nifedipine (10(-6) M), a calcium channel blocker, and thapsigargin (10(-6) M) which inhibits inositol 1,4,5-trisphosphate (IP3) mediated release of [Ca2+]i but abolished by the intracellular calcium antagonist TMB-8 (10(-6) M). The secondary phase was reduced following pretreatment with either nifedipine or the protein kinase C (PKC) antagonist, H-7 (10(-6) M). The PKC agonist PMA (phorbol 12-myristate 13 acetate, 10(-6) M) produced a small rise in basal [Ca2+]i and abolished the GnRH calcium response. The initial calcium response to GnRH therefore involves both an IP3-mediated rise in cytosolic calcium due to the release from intracellular stores and an influx of extracellular calcium through second messenger-operated calcium channels. In contrast the secondary calcium response mainly involves the influx of extracellular calcium through PKC-activated calcium channels. PMID- 1511787 TI - The ratio of mouse insulin I:insulin II does not reflect that of the corresponding preproinsulin mRNAs. AB - Rats and mice both express two, non-allelic, insulin genes. In the rat the ratio of the two preproinsulin mRNAs closely matches that of the mature insulin peptides. The experiments reported here demonstrate that this is not the case in the mouse. The relative amounts of the two murine proinsulin RNAs were measured by an S1 nuclease assay. The ratio of preproinsulin I mRNA to preproinsulin II mRNA was 4:1 in RNA extracted from the pancreas of mice fed ad libitum or fasted for 72 h. A similar value was found in mouse islets of Langerhans after maintenance in tissue culture for 48 h at either 2.8 or 16.7 mM glucose. The ratio of insulin I:insulin II peptides, assessed by separating the two insulins using reversed phase high-performance liquid chromatography, was approximately 1:3 in both pancreas and islets. Thus in the mouse, unlike the rat, the ratio of the two insulin peptides does not reflect that of the two preproinsulin mRNAs. PMID- 1511789 TI - Gonadotropins induce accumulation of insulin-like growth factor I mRNA in pig granulosa cells in vitro. AB - Pig granulosa cells have been shown to synthesize insulin-like growth factor (IGF) I peptide in vitro, and this expression is regulated by gonadotropins via the cAMP pathway. By hybridizing an IGF I cDNA probe with total RNA isolated from pig granulosa cells cultured in vitro, we show that these cells contain two IGF I transcripts of about 0.9 kb and 9 kb in size. Treatment of the cells with gonadotropins (follicle-stimulating hormone, luteinizing hormone) or cAMP agonists (dibutyryl-cAMP, forskolin) induces an accumulation of the transcripts which can be abolished by transcriptional inhibitors, but not by translational inhibitors. We thus provide new evidence that pig granulosa cells are a site of IGF I synthesis, and we conclude that (1) gonadotropins increase IGF I mRNA levels; (2) the accumulation of IGF I mRNA results from an increased transcription; (3) the stimulation of IGF I gene transcription does not require ongoing protein synthesis; (4) these effects of follicle-stimulating hormone can be mimicked by cAMP agonists. PMID- 1511790 TI - Carboxypeptidase H in bovine pituitary gland: soluble forms are not processed at the C-terminus. AB - Carboxypeptidase H (CP-H) has been characterized in anterior and posterior lobes of bovine pituitary with regard to subcellular distribution, enzymatic properties, nature of membrane association, number of forms and C-terminal processing. Anterior lobe contained both soluble and membrane forms of CP-H with similar enzymatic properties after extraction at pH 5.5. The soluble forms represented about 70% of the total activity. Two soluble and two membrane forms, of 53 and 56 kDa, were demonstrated by immunoblotting and after purification. The amount of the 56 kDa soluble form increased with the salt content of the extraction buffer. Endoglycosidase digestions showed that the difference in size was not due to differential N-linked glycosylation and also showed that CP-H oligosaccharides do not become resistant to endoglycosidase H. CP-H in posterior lobe was also composed from about 70% soluble and 30% membrane forms. Only 53 kDa CP-H was detected in soluble and membrane fractions of posterior lobe. All forms of CP-H from both lobes reacted with antiserum directed to the C-terminus. These results do not support previous observations that soluble and membrane forms of CP-H can be distinguished by size and C-terminal processing. PMID- 1511788 TI - Modulation of androgen-responsive gene expression by estrogen. AB - Studies on hormonal action frequently focus on a single hormone. In intact animals, however, genes may respond to the balance of multiple hormones. Therefore, we have studied the mutual influence of sex steroids on eight genes previously known to be testosterone-responsive in kidneys of mice. A variety of responses to estrogen were recorded. Effects occurred primarily at the transcriptional level although in several cases there was also evidence of decreased mRNA stability. Estrogen did not affect the nuclear location of the androgen receptor. Apparently each gene interacts with both androgen-receptor complex and estrogen-receptor complex, and the ultimate outcome depends on each gene's detailed regulatory structure. PMID- 1511791 TI - Too few cooks: too many cooks. PMID- 1511792 TI - Improvement in walking performance of children with cerebral palsy: preliminary results. AB - The effect of four to six months use of ankle-foot orthoses (AFOs) and balance training was determined for six children with cerebral palsy. The six consecutively referred patients had spastic diplegia or hemiplegia, with hyperextension of the knee, and had accurate voluntary control of the trunk and hips. Fixed AFOs were adjusted to control the position of the ground reaction force in relation to the knees. Balance training was targeted to the knees. All children showed a decrease in the magnitude of the knee-extending moment arm toward normal when barefoot. Improvement was noted in foot-ground contact for three children and of stance-phase posture for three. These improvements were not related to range of motion or speed, and a motor learning effect is proposed. The value of monitoring the moment arm is emphasised. PMID- 1511794 TI - Tethered cord syndrome in myelodysplasia: correlation between level of lesion and height at time of presentation. AB - The purpose of this study was to determine whether the onset of tethered cord syndrome is related to the level of the myelomeningocele (MMC) (sacral, low lumbar, high lumbar or thoracic) and the height and age of the patient at time of presentation. Of 163 patients followed, 18 underwent corrective surgery for symptomatic tethered cord syndrome. The level of lesion at time of presentation correlated highly with height and age. The mean height and age for each level at the time of surgery were: sacral 134.5cm, 9.3 years; low lumbar: 124cm, 9.9 years; high lumbar: 108cm, 4.9 years; thoracic: 92.4cm, 4.7 years. The author concludes that the sensorimotor level of patients with MMC is a useful clue in predicting the onset of symptoms related to tethered cord syndrome. PMID- 1511793 TI - Ventilation and swallowing interactions of normal children and children with cerebral palsy. AB - The respiratory inductance plethysmograph was used to analyse the ventilatory cycle during drinking, chewing and swallowing of normal and cerebral-palsied children aged between five and 12 years. 33 children were divided equally into three groups: normal, spastic CP and athetoid CP. A few of the children with spastic CP and over half of those with athetoid CP were unable to perform the 'big breath' task. In the remaining trials, the children with CP held their breath for a shorter time than normal children. Many children with CP required multiple swallows to consume 5mL of liquid. In the majority of trials, normal children swallowed liquids at or near the peak of inspiration, whereas the children with CP did not. Supplementary swallows and solid-bolus swallows occurred at any point in the ventilatory cycle in all groups. The children with CP had a greater need to inspire at the end of liquid tasks, especially during the 75mL task. PMID- 1511795 TI - Reciprocal neurological developments of twins discordant for hydrocephalus. AB - Studies of 10 sets of twins discordant for hydrocephalus in early life revealed striking differences in degree and nature of development of verbal vs. non-verbal cognitive functions, birth order, and hand and eye preference. Despite similar (four dizygotic pairs) or identical (six monozygotic pairs) genetic endowment and grossly similar intra- and extra-uterine environmental and socio-economic influences, the consistency of the differences between the hydrocephalic children and their seemingly normal twins indicate systematic differences in pre-, peri- and/or early postnatal organization and development of hemispheric function. Follow-up studies also documented development of above-average intelligence, despite drastically reduced cerebral mantle size in hydrocephalus of early onset. The atypical patterns of development of the non-hydrocephalic twins also confirm previously described qualifications reported in studies of the significance of genetic vs. environmental factors in twins. PMID- 1511796 TI - Congenital Horner syndrome associated with non-cervical neuroblastoma. AB - Horner syndrome may be caused by a neuroblastoma involving the cervical sympathetic nervous system. A two-year-old girl presented with Horner syndrome and a discrete, distant neuroblastoma, suggesting that these two conditions represent a more widespread dysgenesis of the sympathetic nervous system. PMID- 1511797 TI - Migraine and epilepsy. PMID- 1511798 TI - Effect of donor islet mass on metabolic normalization in streptozotocin-diabetic rats. AB - The effect of donor islet mass on the metabolic normalization in streptozotocin diabetic rats was examined by comparing normal control rats with two transplant groups receiving 800 or 2,000 islets intraportally, i.e. grafts containing respectively, 0.8 or 2 million Beta cells at 70% purity. After transplantation, basal glycaemia and daily urine volumes normalized in all recipients and remained normal in both groups over the 20-week follow-up period. After intragastric glucose challenge, the 800-islet group exceeded the normal range of glycaemia at all tested time points (0-120 min) whereas the 2,000-islet group exhibited higher glycaemia only at 15 and 30 min; no deterioration in glucose tolerance occurred during the 20-week follow-up. Both transplant groups presented lower serum fructosamine levels than diabetic control rats, normal levels being maintained only in the 2000-islet group. At post-transplantation week 21, both recipient groups exhibited the same body weight as age-matched normal control rats, but their serum triglyceride levels were significantly higher. Hepatic insulin contents were comparable to the insulin contents of the grafts at the time of implantation, representing 16 or 40% of the pancreatic insulin content in the age matched control rats. Although islet grafts with 0.8 million Beta cells can restore basal glycaemia in adult streptozotocin-diabetic rats, implants of 2 million Beta cells are necessary to correct other parameters of glucose homeostasis. The present data indicate the need of determining the number of grafted Beta cells in studies on the metabolic outcome of islet cell transplantation. DNA content and percentage of Beta cells in the graft are proposed as useful parameters. PMID- 1511799 TI - Glucose modulation of aldose reductase mRNA expression and its activity in cultured calf pulmonary artery endothelial cells. AB - We examined the effect of glucose on aldose reductase mRNA expression and its activity in calf pulmonary artery endothelial cells. After the cells were exposed to 18 mmol/l glucose, aldose reductase mRNA expression began to increase at 6 h, reached a maximum (about 2.4-fold increase) at 12 h, and thereafter gradually decreased. Aldose reductase activity was found to strongly correlate with aldose reductase mRNA expression after cells were exposed to 18 mmol/l glucose. In contrast, aldose reductase mRNA expression was significantly decreased following exposure to 55 mmol/l glucose. Aldose reductase activity was also decreased at 24 h after 55 mmol/l glucose. The increase in aldose reductase mRNA level caused by glucose was inhibited by 1 microgram/ml of actinomycin D. These phenomena appear to be glucose-specific since neither 3-O-methylglucose nor fructose affected the levels of aldose reductase mRNA. We clearly demonstrate that aldose reductase mRNA level and its activity are modulated by glucose in calf pulmonary artery endothelial cells. Our data suggest that activation of aldose reductase in endothelial cells may contribute to the development of diabetic macroangiopathy. PMID- 1511800 TI - Human pancreatic beta-cell glucokinase: cDNA sequence and localization of the polymorphic gene to chromosome 7, band p 13. AB - The glucose phosphorylating enzyme glucokinase plays an important role in the regulation of glucose homeostasis. Studies in rodents indicate that pancreatic Beta cells and hepatocytes express different isoforms of this protein as a consequence of the presence of tissue-specific promoters and exon 1 sequences which are spliced to a shared group of nine exons which encode most of the mRNA and protein. Here, we report the isolation and characterization of cDNA clones encoding human Beta-cell glucokinase. The sequence of human Beta-cell glucokinase shows 97% amino acid identity with that of the cognate rat protein. We also mapped the human glucokinase gene to the short arm of chromosome 7 by analysing its segregation in a panel of reduced human-mouse somatic cell hybrids. In situ hybridization to metaphase chromosomes confirmed the localization of the human glucokinase gene to chromosome 7 and indicated that it was in band p 13. A microsatellite DNA polymorphism that can be typed using the polymerase chain reaction was identified upstream of exon 1 a, the Beta-cell specific first exon. The glucokinase cDNA clone and highly informative DNA polymorphism will be useful for examining the role of this gene in the pathogenesis of diabetes mellitus. PMID- 1511801 TI - Autoantibodies to 64,000-M(r) islet cell protein in long-term type 1 (insulin dependent) diabetic patients. AB - Autoantibodies to the 64,000-M(r) (64K) islet cell protein, identified as glutamic acid decarboxylase, were assayed in 46 Type 1 (insulin-dependent) diabetic patients with a disease duration of more than 5 years. Of 46 Type 1 diabetic patients, 18 (39.1%) were found to be positive for 64K antibodies and 12 of these patients had been diagnosed with autoimmune thyroid disease. Serum C peptide levels were not detectable in 15 of 18 patients positive for 64K antibodies. The samples were also tested for titres of islet cell antibodies. Islet cell antibodies were detected in 15 (32.6%) of the 46 patients and all the islet cell antibody positive patients were also found to be positive for 64K antibodies. Furthermore, of these 15 patients 12 had previously been diagnosed with autoimmune thyroid disease. A correlation between levels of 64K antibodies and islet cell antibody titre revealed that higher levels of 64K antibodies were observed in patients who had higher islet cell antibody titre. These results demonstrate that most long-term Type 1 diabetic patients with 64K antibodies were also positive for islet cell antibodies complicated by autoimmune thyroid disease. PMID- 1511802 TI - Twenty-four-hour energy expenditure in Pima Indians with type 2 (non-insulin dependent) diabetes mellitus. AB - To assess the impact of Type 2 (non-insulin-dependent) diabetes mellitus on energy metabolism, 24-h energy expenditure, basal metabolic rate and sleeping metabolic rate were measured in a respiratory chamber in 151 Pima Indians, 102 with normal glucose tolerance (67 male/35 female, (mean +/- SD) 28 +/- 7 years, 99 +/- 24 kg, 32 +/- 9% body fat) and in 49 with Type 2 diabetes (22 male/27 female, 35 +/- 11 years, 107 +/- 33 kg, 39 +/- 7% body fat), after at least 3 days on a weight maintaining diet. After adjustment for differences in fat-free mass, fat mass, age and sex, 24-h energy expenditure, basal metabolic rate and sleeping metabolic rate were significantly higher in diabetic patients than in control subjects (72 kcal/day, p less than 0.05; 99 kcal/day, p less than 0.005; 99 kcal/day, p less than 0.001 respectively). Spontaneous physical activity was similar in both groups whereas the thermic effect of food, calculated as the mean energy expenditure corrected for activity throughout the day above sleeping metabolic rate and expressed as a percentage of energy intake, was significantly lower in Type 2 diabetic patients (17.1 +/- 7.1 vs 19.8 +/- 5.6%, p less than 0.05). Adjusted values of 24-h energy expenditure, basal metabolic rate and sleeping metabolic rate were correlated with hepatic endogenous glucose production (r = 0.22, p less than 0.05; r = 0.22, p less than 0.05; r = 0.31, p less than 0.01 respectively). Therefore, increased basal and sleeping metabolic rates, resulting in increased 24-h sedentary energy expenditure may play a role in the weight loss so often observed in Type 2 diabetic subjects in addition to the energy loss from glycosuria. PMID- 1511803 TI - Diabetes mellitus, impaired glucose tolerance and mortality among elderly men: the Finnish cohorts of the Seven Countries Study. AB - We studied the association of glucose intolerance with total and cause-specific mortality during a 5-year follow-up of 637 elderly Finnish men aged 65 to 84 years. Total mortality was 276 per 1000 for men aged 65 to 74 years and 537 per 1000 for men aged 75 to 84 years. Five-year total mortality adjusted for age was 364 per 1000 in diabetic men, 234 per 1000 in men with impaired glucose tolerance and 209 per 1000 in men with normal glucose tolerance. The relative risk of death among diabetic men was 2.10 (95% confidence interval 1.26 to 3.49) and among men with impaired glucose tolerance 1.17 (95% confidence interval 0.71 to 1.94) times higher compared with men with normal glucose tolerance. Cardiovascular disease was the most common cause of death in every glucose tolerance group. The multivariate adjusted relative risk of cardiovascular death was increased (1.55) in diabetic patients, albeit non-significantly (95% confidence interval 0.84 to 2.85). Diabetes resulted in an increased risk of cardiovascular mortality among men aged 65-74 years but not among the 75- 84-year-old men. Relative risk of death from non-cardiovascular causes was slightly increased among diabetic subjects. In conclusion, diabetes mellitus is a significant determinant of mortality among elderly Finnish men. PMID- 1511805 TI - Impaired endothelium-dependent and independent vasodilation in patients with type 2 (non-insulin-dependent) diabetes mellitus. AB - The endothelium plays a pivotal role in modulating the reactivity of vascular smooth muscle through the formation of several vasoactive substances. We examined the effects of endothelium-dependent and independent vasodilators on forearm blood flow in 29 patients with Type 2 (non-insulin-dependent) diabetes mellitus and in 21 control subjects, using venous occlusion plethysmography. Via a brachial artery cannula, increasing amounts of acetylcholine and glyceryl trinitrate were infused in doses of 60, 120, 180 and 240 mmol per min and 3, 6 and 9 nmol per min respectively. NG monomethyl-L-arginine, a stereospecific inhibitor of endothelium derived relaxing factor, was infused to inhibit basal and stimulated release of this dilator substance. Reactive hyperaemic forearm blood flow did not differ between groups. Forearm blood flow responses to each dose of acetylcholine were significantly greater in control than diabetic subjects (p less than 0.01 for all doses). NG monomethyl-L-arginine attenuated forearm blood flow from maximal stimulated values when responses were compared with the natural decline to acetylcholine in forearm flow in both control and diabetic subjects (p less than 0.05 for both groups), but had no effect on basal blood flow responses. Forearm blood flow responses to each dose of glyceryl trinitrate were significantly greater in control than diabetic subjects (p less than 0.05 for all). These data provide evidence for endothelial and smooth muscle dysfunction in diabetes which may have important therapeutic implications. PMID- 1511804 TI - Hyperinsulinaemia is not a major coronary risk factor in elderly men. The study of men born in 1913. AB - Insulin and insulin resistance have attracted considerable interest as possible risk factors for coronary heart disease during the last decade. We therefore examined the 8-year incidence of coronary heart disease in 595 67-year-old men in relation to baseline insulin and other risk factors. The incidence of coronary heart disease increased from 9% among non-diabetic men to 13.5% among those with impaired glucose tolerance, 12.9% among newly-detected diabetic men and up to 31.3% among men with known diabetes. The incidence of coronary heart disease was related to fasting blood glucose and 1 h and 2 h blood glucose during the oral glucose tolerance test and to serum cholesterol and serum triglycerides. Fasting serum insulin was of borderline significance for the risk of coronary heart disease. When known diabetic subjects were excluded only serum cholesterol and serum triglycerides remained as statistically significant risk factors. Among diabetic subjects (known and newly-detected) only blood glucose was related to the risk of coronary heart disease. In multivariate analyses the different degrees of glucose intolerance or fasting blood glucose were independently related to the risk of coronary heart disease (p = 0.008-0.010). Serum triglycerides were also an independent risk factor in three out of four multivariate models (p = 0.02-0.09). Fasting serum insulin was not an independent risk factor. These findings do not support the hypothesis that hyperinsulinaemia is a major risk factor for coronary heart disease in elderly men. Hyperglycaemia (or diabetes mellitus) seems to be the most important risk factor. PMID- 1511806 TI - In vivo insulin action and muscle glycogen synthase activity in type 2 (non insulin-dependent) diabetes mellitus: effects of diet treatment. AB - Insulin resistant glucose metabolism is a key element in the pathogenesis of Type 2 (non-insulin-dependent) diabetes mellitus. Insulin resistance may be of both primary (genetic) and secondary (metabolic) origin. Before and after diet-induced improvement of glycaemic control seven obese patients with newly-diagnosed Type 2 diabetes were studied with the euglycaemic clamp technique in combination with indirect calorimetry and forearm glucose balance. Muscle biopsies were obtained in the basal state and again after 3 h of hyperinsulinaemia (200 mU/l) for studies of insulin receptor and glycogen synthase activities. Similar studies were performed in seven matched control subjects. Insulin-stimulated glucose utilization improved from 110 +/- 11 to 183 +/- 23 mg.m-2.min-1 (p less than 0.03); control subjects: 219 +/- 23 mg.m-2.min-1 (p = NS, vs post-diet Type 2 diabetes). Non-oxidative glucose disposal increased from 74 +/- 17 to 138 +/- 19 mg.m-2.min-1 (p less than 0.03), control subjects: 159 +/- 22 mg.m-2.min-1 (p = NS, vs post-diet Type 2 diabetic patients). Forearm blood glucose uptake during hyperinsulinaemia increased from 1.58 +/- 0.54 to 3.35 +/- 0.23 mumol.l-1.min-1 (p less than 0.05), control subjects: 2.99 +/- 0.86 mumol.l-1.min-1 (p = NS, vs post-diet Type 2 diabetes). After diet therapy the increase in insulin sensitivity correlated with reductions in fasting plasma glucose levels (r = 0.97, p less than 0.001), reductions in serum fructosamine (r = 0.77, p less than 0.05), and weight loss (r = 0.78, p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1511807 TI - Relationship of glucose intolerance and hyperinsulinaemia to body fat pattern in south Asians and Europeans. AB - Type 2 (non-insulin-dependent) diabetes mellitus and insulin resistance are associated with centrally-distributed obesity. These disturbances are especially prevalent in people of South Asian (Indian, Pakistani and Bangladeshi) descent. We examined the relationship of glucose intolerance to body fat pattern in a population survey of 2936 men and 537 women of South Asian and European origin living in London, UK. In both groups glucose intolerance (defined as diabetes or impaired glucose tolerance) was more strongly associated with waist-hip girth ratio than with skinfolds or body mass index. The associations between body mass index and glucose intolerance were fully accounted for by waist-hip ratio. In European men with normal glucose tolerance fasting insulin levels were more strongly correlated with body mass index than with waist-hip ratio. Physical activity scores were lower in South Asians than in Europeans but no statistically significant associations between glucose intolerance and low physical activity were detectable. Leisure-time physical activity scores were inversely correlated with 2 h insulin levels in both groups. In contrast with other studies these results suggest that a specific effect of intra-abdominal fat deposition underlies the association between glucose intolerance and obesity. The association between hyperinsulinaemia and obesity is less specific for centrally distributed fat. When measured appropriately waist-hip ratio is the most valid anthropometric index for identifying individuals whose obesity predisposes them to glucose intolerance. PMID- 1511808 TI - Islet cell antibody heterogeneity among type 1 (insulin-dependent) diabetic patients. AB - Conventional detection of islet cell antibodies is based on indirect immunofluorescence performed on frozen human pancreas sections. The number and nature of epitopes recognized by antibodies detected by such techniques are unknown. To determine the existence of heterogeneous fluorescence patterns of islet cell antibodies on pancreatic sections, we selected two sera showing a distinctive granular fluorescence. We then tested random sera from patients with Type 1 (insulin-dependent) diabetes mellitus for their ability to block ultimate binding of fluorescein isothiocyanate-labelled immunoglobulins purified from these two sera with a characteristic granular pattern. Among 102 subjects with recent-onset Type 1 diabetes, 79 had detectable anti-islet cell antibodies; 21 showed complete blockade of the binding to islets of granular fluorescein isothiocyanate-labelled immunoglobulins. The majority of these 21 patients were women carrying a DR3 non-DR4 DQB1*0201 allele, with under-representation of DRB1*0402 and 0405. Discrimination between islet cell antigenic specificities may help in identifying islet cell autoantibodies in autoimmune Type 1 diabetes. PMID- 1511809 TI - Fifth International Serum Exchange Workshop for Insulin Autoantibody (IAA) Standardization. The Immunology and Diabetes Workshops and participating laboratories. PMID- 1511810 TI - Plasma human amylin levels. PMID- 1511811 TI - Prospective evaluation of complications in an endoscopy unit: use of the A/S/G/E quality care guidelines. AB - In 1989, the American Society for Gastrointestinal Endoscopy released a quality assurance monograph in which a procedure review process was outlined. The major elements of the program for quality assurance in gastrointestinal endoscopy included: (1) procedure reports, (2) an endoscopic unit record, and (3) a procedure review. This study was designed to use the procedure review process to determine the incidence of complications, to identify quality assurance issues, and to determine whether audits and/or studies would result from this process. To make a meaningful interpretation as to what constitutes an important complication, a classification to define potential problems was established. Using this classification, a complication was identified in 64 of 3287 procedures (1.9%). These complications were discussed in a monthly morbidity and mortality conference. Additionally, 21 quality assurance issues were identified that led to four studies addressing these quality assurance issues. PMID- 1511812 TI - Oxygenating mouthguard alleviates hypoxia during gastroscopy. AB - A randomized study was carried out to determine the effect of oxygen (3 liters/min) via a novel oxygenating mouthguard (Oxyguard) on arterial oxygenation in 242 intravenously sedated patients undergoing gastroscopy. In another group of 21 patients, a randomized crossover study of arterial oxygen saturation using either the standard mouthguard or the oxygenating mouthguard (3 liters/min) was conducted. Significant O2 desaturation (pulse oximeter reading less than 90%) occurred in 25% of patients on room air but only 3% of those on oxygen (p less than 0.001). Severe desaturation (reading less than 85%) occurred in 5% of patients on room air but was prevented by the oxygenating mouthguard. Minimum oxygen saturation levels were significantly higher in patients on oxygen (90.5 +/ 0.3%) than on air (86.5 +/- 0.5%; p less than 0.001). In the crossover group, O2 saturation was uniformly higher in the recordings of all patients using the oxygenating mouthguard. In conclusion, administration of oxygen via the oxygenating mouthguard alleviates hypoxemia during gastroscopy and prevents severe oxygen desaturation. However, hypoxemia may occur even during use of supplemental oxygen. Hence, monitoring of arterial oxygenation is recommended. PMID- 1511813 TI - Supplemental low flow oxygen prevents hypoxia during endoscopic cholangiopancreatography. AB - Administration of continuous oxygen during ERCP may prevent hypoxia. Oxygen saturation was recorded using pulse oximetry in 50 consecutive patients undergoing ERCP. Patients were randomly allocated to receive no oxygen or low flow oxygen (2 liters/min) via nasal prongs or nasopharyngeal cannula. Oxygen saturation fell below 90% in 47% of patients not receiving oxygen compared with 0% in those administered oxygen (p less than 0.001). No difference existed in oxygen saturations between those groups receiving supplemental oxygen via nasal prongs or nasopharyngeal cannula. Continuous administration of low flow oxygen is recommended during ERCP. PMID- 1511814 TI - Injection sclerotherapy preceded by esophageal tamponade versus immediate sclerotherapy in arresting active variceal bleeding: a prospective randomized trial. AB - To investigate whether Sengstaken-Blakemore tube tamponade is needed before emergency sclerotherapy, 60 patients with active esophageal variceal bleeding were randomized to receive either immediate injection sclerotherapy (group A) or sclerotherapy preceded by balloon tamponade (group B). Three patients in group A (10%) were completely inaccessible to sclerotherapy. Initial success in stopping bleeding at 24 hours after sclerotherapy was 76% in group A and 81% in group B (p = 0.89). Re-bleeding rate was 27% in group A versus 50% in group B (p = 0.11). Blood requirement was significantly less in group A (3.7 +/- 2.5 units vs. 6.2 +/ 3.2 units, p less than 0.01). Major complications were also significantly less frequently encountered in group A than in group B (14% vs. 39%, p less than 0.05). In-hospital mortality was 24% in group A and 42% in group B (p = 0.14). We conclude that the efficacy of immediate sclerotherapy is comparable to that of delayed sclerotherapy preceded by balloon tamponade. Additionally, significantly less blood requirement and fewer complications were noted in the immediate sclerotherapy group. Thus, emergency sclerotherapy without prior balloon tamponade is feasible and recommended in most patients with acute esophageal variceal hemorrhage. PMID- 1511815 TI - A prospective study of the ability of three endoscopic classifications to predict hemorrhage from esophageal varices. AB - Hemorrhage from esophageal varices in cirrhotics is a frequent event with high mortality in spite of therapy. Preventive sclerotherapy seems to be beneficial only if the patient's bleeding risk is higher than 40 to 50% a year. A series of 320 patients with esophageal varices without previous bleeding was studied prospectively; the varices were classified according to three widely used endoscopic classifications. During follow-up (6 to 36 months, average 14 months), hemorrhage occurred in 49 patients (15.3%) of whom 30 (61.2%) bled from varices (8.2 and 11.0% at 12 and 24 months, respectively). At the same time intervals, mortality of the entire population studied was 18.0 and 23.8%, respectively, of which one third was directly due to hemorrhage. With all three classifications, the higher the degree of bleeding risk, the greater the actual percentage of hemorrhages recorded; however, it never reached 40% a year. In predicting the bleeding event, Dagradi's classification proved more sensitive than JRSPH or NIEC, but the latter classifications were more specific and assessed a higher predictive value for a positive test. Endoscopic observation probably needs integration with other methods if a reliable bleeding prediction is to be made. PMID- 1511816 TI - Endoscopic therapy in patients with pancreas divisum and acute pancreatitis: a prospective, randomized, controlled clinical trial. AB - Endoscopic endoprosthesis (stent) placement across the minor papilla has been shown to be beneficial in reducing abdominal pain and episodes of pancreatitis in a small group of patients with pancreas divisum and acute recurrent pancreatitis. In a randomized, controlled clinical trial, 19 patients with pancreas divisum and at least 2 documented episodes of pancreatitis were randomized to either dorsal duct stent placement (10 patients--5 women and 5 men) or controls (9 patients--6 women and 3 men). All other causes of pancreatitis were excluded. Patients were followed at 4-month intervals for evaluation and/or stent exchange during a 1 year period. The following criteria were evaluated during follow-up: number of hospitalizations or emergency room visits, the number of documented episodes of pancreatitis, and gradation of the patient's overall general feeling based on a visual analog scale. Mean follow-up times in the stent and control groups were 28.6 and 31.5 months, respectively (p greater than 0.05, NS). No patients in the stent group required hospitalization or emergency room visits for abdominal pain only during and following the treatment period. However, in the control group there were five hospitalizations and two emergency room visits for abdominal pain during a similar period (p less than 0.05). Pancreatitis was documented with an elevated amylase twice the normal range, one time in the stent group and seven times in the control group (p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1511818 TI - Correlation of basal sphincter pressures measured from the bile duct and the pancreatic duct in patients with suspected sphincter of Oddi dysfunction. AB - If basal sphincter of Oddi pressures measured from the pancreatic duct and the bile duct are essentially equal, then measurement of basal pressures from only one duct would be adequate in evaluating sphincter of Oddi dysfunction. We report a series of 88 patients whom we evaluated with sphincter of Oddi manometry. Cannulation of both the biliary sphincter segment and pancreatic sphincter segment was achieved in these patients. Basal sphincter pressures were measured (normal, less than 40 mm Hg). In 45 of the 88 patients (51%), normal sphincter of Oddi basal pressures were seen in both ducts. Elevated basal sphincter of Oddi pressures were seen in both ducts in 28 of 88 patients (32%). In 15 of 88 cases (17%) there was an elevation of only one sphincter segment. Elevation in only the biliary sphincter segment occurred in 7 of 88 patients (8%). Elevation in the pancreatic sphincter segment alone occurred in 8 of 88 patients (9%). We conclude that sphincter of Oddi manometry of both the pancreatic and bile ducts is needed if complete manometric information is desired. PMID- 1511817 TI - Delayed biliary drainage is common in asymptomatic post-cholecystectomy volunteers. AB - A commonly used diagnostic criterion for sphincter of Oddi dysfunction is delayed drainage of contrast media from the bile ducts at endoscopic retrograde cholangiography (ERC), which is defined as the persistence of contrast greater than 45 min after injection. We performed ERC in 11 asymptomatic post cholecystectomy volunteers for the purpose of evaluating biliary drainage time. In an attempt to more accurately quantify emptying, concomitant scintigraphy was performed at the time of ERC and contrast drainage. Sufficient contrast mixed with technetium-99m sulfur colloid to completely fill out the intra-hepatic tree was injected (mean volume, 9 ml) and the volunteers remained in the prone position during imaging. The length of time from cholecystectomy, bile duct size, volume of contrast injected, and scintigraphic T1/2s did not correlate with drainage time at ERC. At 45 min after injection the degree of residual contrast filling was scored as: empty in three volunteers, almost empty in one, one-fourth full in 5, and one-half full in two. Therefore, 7 of the 11 asymptomatic volunteers (63%) had delayed drainage. Even if more stringent criteria for delayed drainage were used (ducts one-half filled), 2 of the 11 (18%) had abnormal drainage. The frequent occurrence of delayed drainage in these asymptomatic post-cholecystectomy volunteers challenges the validity of the 45 min delayed drainage criterion for sphincter of Oddi dysfunction. PMID- 1511819 TI - Bacteremia following diagnostic and therapeutic ERCP. AB - The occurrence of bacteremia in association with diagnostic or therapeutic ERCP was studied in 180 patients undergoing a total of 194 examinations. Nineteen (15%) of 126 diagnostic procedures and 18 (27%) of 68 therapeutic procedures were associated with bacteremia (p less than 0.1). Nine patients had polymicrobial bacteremia and a total of 16 species were detected. Different streptococci, mainly alpha-hemolytic, were the most common bacteria which were identified in 38% of the bacteremic patients. There were no significant differences with regard to the occurrence of fever, pancreatitis, or septic complications between the diagnostic and therapeutic groups of patients. Neither did the complication rate in patients with bacteremia differ from that in patients without bacteremia, whether the procedure was diagnostic or therapeutic. Complication rates did not differ between patients with and patients without pancreaticobiliary obstruction. However, the majority of patients with biliary stasis had drainage with relief of the obstruction at the time of the diagnostic ERCP. We conclude that general routine antibiotic prophylaxis is not indicated in patients undergoing diagnostic or therapeutic ERCP. The question whether such prophylaxis should be given with certain diagnoses or treatments, or in patients with valvular heart disease, remains to be answered in controlled randomized studies. PMID- 1511820 TI - ERCP and endoscopic sphincterotomy in infants and children with jaundice due to common bile duct stones. AB - ERCP was performed in two infants (29 and 62 days old) and eight children (5 to 12 years old) with jaundice due to common bile duct stones. Seven patients had hemolytic anemia and three patients had a family history of gallstone disease. Successful cannulation of the common bile duct demonstrating stones was accomplished in all patients. Four patients had coexisting gallstones and were treated surgically. Six children who had previously undergone cholecystectomy were treated by endoscopic sphincterotomy and stone extraction without complication. We believe that ERCP should be utilized by expert endoscopists in children with evidence of extra-hepatic cholestasis, and endoscopic sphincterotomy should be the treatment of choice in children who have previously undergone cholecystectomy, and who are jaundiced secondary to common bile duct stones. PMID- 1511821 TI - Comparison of 10 French gauge stent with 11.5 French gauge stent in patients with biliary tract diseases. AB - We retrospectively compared the efficacy and complications of 10 F biliary stents with 11.5 F stents in the management of malignant and benign biliary tract diseases. Thirty-three patients treated with 10 F stents inserted on 46 occasions and 30 patients with 11.5 F stents inserted on 43 occasions were evaluated. The success of insertion, relief of jaundice, decline in total bilirubin, stent survival, and complications due to stents were compared. Patients with multiple stents, preoperative biliary drainage, stents smaller than 10 F, larger than 11.5 F, nasobiliary catheter drainage, and percutaneous biliary drainage were excluded. When comparing 10 F stents to 11.5 F stents, the success of insertion was 85% vs. 79% (p = 0.52), relief of jaundice was 88% vs. 90% (p = 0.79), and the decline in total bilirubin was 7.4 mg/100 ml vs. 8.3 mg/100 ml (p = 0.67). The complications, including stent clogging, cholangitis, stent migration, and pancreatitis occurred on seven occasions in patients with 10 F stents and on six occasions in patients with 11.5 F stents. This difference was statistically not significant (p = 0.87). We conclude that 10 F stents have the same success rate and complication rate as 11.5 F stents in the management of biliary tract diseases, and offer no significant advantage. PMID- 1511822 TI - Local staging and assessment of resectability in carcinoma of the esophagus, stomach, and duodenum by endoscopic ultrasonography. AB - Eighty-eight patients with carcinoma of the esophagus (N = 44), stomach (N = 41), and duodenum (N = 3) who underwent surgery were pre-operatively examined by endoscopic ultrasonography (EUS). The ability of EUS to accurately predict the T stage and the N stage was 82% and 70% for esophageal carcinoma, 71% and 75% for gastric cancer, and 100% and 66% for duodenal malignancy. In esophageal carcinoma, the accuracy of T staging was only slightly lower in cases with non traversable tumor stenoses (77%) compared with traversable carcinomas (84%). This was probably due to the fact that all non-traversable tumors were either in stage T3 or T4. The accuracy of EUS in predicting the stages T1 to T3, which correspond to R0 resectability (no macroscopic or microscopic tumor remains), was 92% for adenocarcinoma of the distal esophagus and 85% for gastric cancer. However, in squamous cell carcinoma of the esophagus, R0 resection was possible in only 66% of all cases, whereas EUS predicted an 84% R0 resection rate. In adenocarcinoma of the distal esophagus and stomach, EUS prediction of stages T1 to T3 correlated well with the actual rate of R0 resection. These results show that EUS is a reliable diagnostic method for the local staging of upper gastrointestinal cancer. Its impact on treatment and hence on prognosis of patients with these malignancies has yet to be determined. PMID- 1511823 TI - Endoscopic ultrasound in the pre-operative staging of rectal carcinoma. AB - Endoscopic ultrasound (EUS) was performed prospectively to stage 45 patients with rectal cancer. Patients were staged utilizing the TNM staging system. All patients subsequently underwent surgical resection with independent histopathologic staging. Depth of invasion was accurately predicted in 40 of 45 patients (89%). Presence or absence of lymph node metastasis was correctly determined in 34 of 45 patients (79%). EUS is an accurate method for local staging of rectal cancer. PMID- 1511824 TI - Colonoscopic snare polypectomy: analysis of 1485 resections comparing two types of current. AB - The complications related to 1485 colonic snare polypectomies were analyzed according to the type of current which was used for resection. From January 1982 to August 1986 (period 1), blended current was used in 758 snare polypectomies, while continuous coagulation current was applied in 727 polypectomies from September 1986 to October 1989 (period 2). The incidence of complications observed in the entire series was low, consisting of 0.26% perforations and 0.9% major hemorrhages. There were no deaths in this series. Twelve of 14 hemorrhages occurred after resection of polyps larger than 1 cm. Although the incidence of complications was not statistically different in the two groups, there was a significant difference in the timing of hemorrhages. All of the major hemorrhages were immediate (eight) when the blended current was used, but delayed (six; from 2 to 8 days after polyp resection), when pure coagulation current was applied. PMID- 1511825 TI - Association between histologic type of polyp and carcinoma in the stomach. AB - During a 5-year period, we examined by endoscopy or surgery 2634 stomachs: 2536 (group A) were free of lesions commonly recognized as mucosal "polyps"; 74 (group B) exhibited hyperplastic polyps; and 24 (group C) were found with neoplastic (adenomatous) polyps. Carcinomas were present in 318 (12.5%) of specimens in group A, compared with 10 (13.5%) in group B and 20 (83.3%) in group C. In the third group, 14 carcinomas were encountered within polyps, and 4 carcinomas occurred separately. The frequency of cancer associated with neoplastic polyps was relatively low (1 of 3) in patients younger than 50 years, but significantly high (19 of 21) in older patients. This series confirms the prevailing concept that patients harboring gastric adenomatous polyps are at distinct risk of gastric carcinoma, a risk that sharply rises with age. We conclude that patients found with gastric adenomatous polyps should be subject to careful and continued surveillance to ensure that supervening carcinoma be detected at the earliest possible phase. PMID- 1511826 TI - Ultrasonic esophagoprobe (prototype 1). PMID- 1511827 TI - A new coated self-expanding metal stent for malignant esophageal strictures. PMID- 1511828 TI - Relief of tumorous obstruction of a metal biliary stent with palliative intraluminal iridium-192 therapy. PMID- 1511829 TI - Adenoma of the common bile duct: endoscopic diagnosis and resection. PMID- 1511830 TI - Re-establishment of biliary tract continuity by a combined ERCP and PTC approach after iatrogenic common bile duct ligation. PMID- 1511831 TI - Endoscopic balloon dilation of tuberculous duodenal strictures. PMID- 1511832 TI - Savary dilation of antral stricture from lye ingestion. PMID- 1511834 TI - Training in ERCP. PMID- 1511833 TI - Who is for supplemental oxygen? PMID- 1511835 TI - Direct current electrotherapy of symptomatic hemorrhoid disease. PMID- 1511836 TI - Parotid swelling after endoscopy. PMID- 1511837 TI - Caustic colitis due to formalin enema. PMID- 1511838 TI - Colonoscopic diagnosis of an appendiceal villous adenoma. PMID- 1511839 TI - Hemorrhage from fistula between duodenal cap and hepatic artery aneurysm. PMID- 1511840 TI - Esophageal intubation with the side-viewing endoscope. PMID- 1511841 TI - Portal vein filling: a rare complication associated with ERCP for endoscopic biliary stent placement. PMID- 1511842 TI - Do adenosine A3 receptors exist? AB - 1. It has been suggested that adenosine A1 receptors may be sub-divided into A1 and A3 types, based on the relative potencies of 5'-N-ethylcarboxamidoadenosine (NECA) and selected N6-substituted adenosine analogues. At A1 receptors (rat adipocytes) N6-phenylisopropyladenosine (PIA) was reported to be approx. 100-fold more potent than NECA, whereas the compounds were equipotent at A3 receptors (those in cardiac and neuronal preparations). 2. The study reported here has systematically evaluated this proposal, the rank orders of potency of NECA, R- and S-PIA, N6-cyclopentyladenosine (CPA) and N6-cyclohexyladenosine (CHA) being determined in rat adipocytes, guinea-pig ileum and rat and guinea-pig atria. 3. R PIA, CHA and CPA were found to have consistent potencies relative to NECA across all 6 tissues, including rat adipocytes. The rank order was CPA greater than or equal to CHA, R-PIA greater than or equal to NECA greater than S-PIA. 4. We conclude that the relative potencies of these agonists do not support the concept that adenosine A1 receptors in rat adipocytes differ from those in neuronal and cardiac tissues. PMID- 1511843 TI - Assessment of a model for the opposing effects of N-ethylmaleimide on the affinity of muscarinic agonists for M2 receptors. AB - 1. Homogenates of guinea pig right atrium (M2 receptors) were treated with N ethylmaleimide, after which the ability of carbachol to inhibit binding of [3H]quinuclidinyl benzilate was studied. 2. At 37 degrees C, 10(-4) M and 10(-3) M, but not 10(-5) M, N-ethylmaleimide increased the affinity of carbachol for the receptor. At 2 degrees C, 10(-5) M and 10(-4) M, but not 10(-3) M, N ethylmaleimide decreased carbachol affinity. At 2 degrees C, after the homogenate had been incubated at 37 degrees C without N-ethylmaleimide, 10(-5) M N ethylmaleimide decreased carbachol affinity, as at 2 degrees C without preincubation, but 10(-3) M N-ethylmaleimide increased carbachol affinity, as at 37 degrees C. 10(-4) M N-ethylmaleimide was without effect. 3. The results are discussed with respect to a previously proposed model in which N-ethylmaleimide interacts with two sites, causing an increase or decrease in agonist affinity respectively. PMID- 1511844 TI - REM sleep deprivation decreases apomorphine-induced stimulation of locomotor activity but not stereotyped behavior in mice. AB - 1. Effects of rapid eye movement (REM) sleep deprivation on central dopaminergic system were investigated by testing the behavioral responses to apomorphine and brain dopamine metabolism in mice. 2. REM sleep deprivation for 48 hr significantly suppressed apomorphine.HCl (3.0 and 6.0 mg/kg, i.p.)-stimulated spontaneous locomotor activity without affecting the intensity of stereotyped behavior. 3. Neither the latency of nociceptive response in a hot-plate test nor the duration of pentobarbital-induced sleep was changed by REM sleep deprivation. 4. Dopamine turnover in the striatum and the nucleus accumbens of REM sleep deprived mice was significantly higher than that of control animals. 5. These results suggest that REM sleep deprivation may decrease the function of postsynaptic dopamine receptor in the mesolimbic but not nigrostriatal dopaminergic system. PMID- 1511845 TI - Endothelium-dependent vasodilation by LP-805, a novel vasodilating agent, on rat thoracic aorta. AB - 1. In rat aortae with [E(+)-tissue] and without [E(-)-tissue] intact endothelium, LP-805 relaxed the preparations precontracted with 35.9 mM K+ and its action in E(+)-tissues was more potent than that in E(-)-tissues. Moreover, the inhibitory action of glibenclamide in E(-)-tissues was more potent than that in E(+) tissues. 2. The relaxing action of LP-805 on E(+)-tissues treated with NG-nitro-L arginine methyl ester (10 microM), a potent inhibitor of nitric oxide synthesis, was the same as that in E(-)-tissues. 3. Methylene blue (10 microM) also inhibited the LP-805 induced relaxation in E(+)-tissues. 4. Indomethacin (10 microM) had no effect on LP-805-induced relaxation in E(+)-tissues. 5. These results suggest that the vasorelaxant action of LP-805 involves the mechanism which causes the release of nitric oxide (NO) from vascular endothelium. PMID- 1511846 TI - Effects of LP-805, a novel vasorelaxant agent, a potassium channel opener, on rat thoracic aorta. AB - 1. In rat thoracic aorta, LP-805 (0.1-10 microM) caused the marked reduction of NE-induced maximum response and relaxed the low K+ (less than 35.9 mM)-induced contraction, in a concentration-dependent manner, but failed to relax the high K+ (65.9 mM)-induced contraction. 2. Glibenclamide (0.3-1 microM) caused a parallel shift of concentration-response curve produced by LP-805 for 25.9 mM K(+)-induced contraction and prevented the LP-805-induced reduction in maximum response evoked by NE in a concentration-dependent manner. 3. Glibenclamide (10 microM) prevented the LP-805 (10 microM)-induced decrease in cytosolic Ca2+ levels which was increased by 1 microM NE or 25.9 mM K+. 4. LP-805 (10 microM) increased basal 86Rb efflux, which was completely inhibited by 10 microM glibenclamide. 5. The results suggest that LP-805 causes a vasorelaxation as a consequence of the decrease in cytosolic Ca2+ levels due to the increase in K+ efflux via opening ATP-dependent K+ channels. PMID- 1511847 TI - Effects of LP-805, a new vasodilating agent, on cytosolic Ca2+ and contraction in vascular smooth muscle of rat aorta. AB - 1. LP-805 (0.1-10 microM) caused the reduction in norepinephrine (NE)-and serotonin (5-HT)-induced maximum response, a parallel shift of the concentration response curve for prostaglandin F2 alpha (PGF2 alpha), in a concentration dependent manner, but not K(+)-induced maximum response. 2. In Ca(2+)-free solution, LP-805 (0.1-10 microM) markedly inhibited the phasic contraction induced by 0.3 microM NE and the contraction induced by Ca2+ (0.1-2 mM) in the presence of 0.3 microM NE, in a concentration-dependent manner. Similar results were obtained in the presence of 5-HT (10 microM) or PGF2 alpha (10 microM). 3. In fura-2 loaded strips, ryanodine (10 microM) and LP-805 (10 microM) abolished 1 microM NE- and 30 microM 5-HT-induced phasic contractions, and inhibited the increase in cytosolic Ca2+ levels by both the agonists in the absence of external Ca2+, but had no influence on the following sustained contractions. 4. The effects of LP-805 on PGF2 alpha-induced Ca2+ transient and large sustained contraction were similar to those of ryanodine. 5. These results suggest that a vasodilatory effect of LP-805 might account for inhibiting the mobilization of external Ca2+ through receptor mediated passway and the Ca2+ release from a ryanodine sensitive Ca2+ store. PMID- 1511848 TI - Systemic administration of baclofen inhibits water intake in rats. AB - 1. The present experiments were carried out to investigate the effects of systemic administration of baclofen on water intake in rats. 2. Baclofen (1, 2 and 4 mg/kg, s.c.) inhibited water intake in 16 hr water-deprived rats in a dose related manner, with maximal effects occurring during the first 30 min after administration. 3. Baclofen (0.25 and 2 mg/kg, s.c.) had no effects on water intake in non-deprived rats. 4. Baclofen (2 mg/kg) inhibited water intake elicited by i.p. injection of hypertonic NaCl in rats. 5. Baclofen (1 mg/kg) did not produce taste aversion in a taste aversion experiment. This indicates that the effects of baclofen on water intake is not due to an aversive effect of the drug. PMID- 1511849 TI - Effects of caffeine on the DNA and protein synthesis of the protein-energy malnourished neonatal cardiac muscle cells in culture. AB - 1. The growth of cardiac cells derived from newborn rats whose dams were either malnourished or malnourished with caffeine during pregnancy was inhibited in culture over the period of 5 days as compared to that of the normally nourished cells. 2. Cells derived from malnourished rats with caffeine added to their diets showed a greater inhibition than those from the malnourished rats not given caffeine. 3. Both DNA and protein synthesis showed an inhibition due to caffeine in a dose-dependent manner using normally nourished cells. 4. In the presence of exogenous 2 mM caffeine, the degree of percent inhibition of DNA and protein synthesis of cells derived from rats malnourished with caffeine was less than that from the rats with malnutrition alone. 5. The present data indicated that malnutrition combined with caffeine during pregnancy exerted a greater negative effect on the nature of cell growth than malnutrition alone and these cells became less sensitive to exogenous caffeine. PMID- 1511850 TI - Effect of aging on contractile response to KCl, norepinephrine and 5 hydroxytryptamine in isolated human basilar artery. AB - 1. We investigated the effect of aging on contractile response in human basilar artery. 2. The maximal contraction caused by KCl, norepinephrine and 5 hydroxytryptamine decreased with age. 3. ED50 value for norepinephrine or 5 hydroxytryptamine did not correlate with age. 4. These results suggest that the decrease in contractile response is due to nonspecific changes in the medial structure of the artery. PMID- 1511851 TI - GABAergic and cholinergic mediation in the antinociceptive action of homotaurine. AB - 1. The role of GABAergic and cholinergic mechanisms in the antinociceptive effect of homotaurine (22.25-111.24 mg/kg i.p.) in chemical (acetic acid) and thermal (tail flick, tail immersion) tests has been studied by means of the interaction with baclofen and anticholinergic drugs. 2. Baclofen (2 mg/kg p.o.) and scopolamine sulfate (2.5 mg/kg i.p.) potentiate the antinociceptive effect of the amino acid in the chemical test. 3. Bicuculline (1 mg/kg i.p.) pretreatment does not modify the antinociceptive effect of homotaurine in the tail immersion and tail flick tests. 4. Scopolamine sulfate and methylnitrate (1 mg/kg i.p.) antagonise the effect of homotaurine (111.24 mg/kg i.p.) in the tail flick test. 5. The above results imply that peripheral GABAB and central cholinergic mechanisms play a role in the antinociceptive effect of homotaurine. PMID- 1511852 TI - Changes in microtubule-associated tau protein in human neuroblastoma cells after phencyclidine. AB - 1. A human neuroblastoma cell line, SH-SY5Y, was used to study the effects of phencyclidine (PCP) on microtubule-associated tau protein, which acts in vivo chiefly to induce the assembly of tubulin and in vitro to promote microtubule polymerization. 2. PCP (1.0 mM) decreased tau protein (50 kD) in the cytoplasmic (supernatant) fraction as well as in the membrane (pellet) fraction. 3. These changes in tau protein were accompanied by decreases of 30-95% in cell number after concentrations of PCP, 0.25-1.0 mM, respectively. 4. After 0.5 mM PCP cytoplasmic and membrane fractions of SH-SY5Y cells showed 100 and 84% increases in total protein, respectively. PMID- 1511853 TI - Dipyridamole induced myocardial recovery after global ischemia. AB - 1. An experimental comparative study on isolated guinea pig hearts was carried out to determine the effect of dipyridamole added to the reperfusion solution on myocardial recovery after global ischemia. 2. After 20 min of normothermic ischemia two groups of solutions: (1) Krebs solution; (2) Krebs + dipyridamole 20 micrograms/l (10 experiments in each group) were used for reperfusion. 3. Postischemic myocardial functions (heart rate, ventricular contractility, heart work) and tissue enzymes (CPK-MB, LDH) were compared with their preischemic values. 4. Addition of dipyridamole 20 micrograms/l to reperfusion solution improved postischemic myocardial functions and decreased myocardial injury. PMID- 1511854 TI - A comparative study on the effect of verapamil and prazosin on the thermoregulatory responses induced by cold or exogenous noradrenaline. AB - 1. Thermoregulatory responses to verapamil (VER; 5 mg/kg/hr) and prazosin (PRA; 0.75 mg/kg/3 hr) were investigated in rabbits exposed to cold (4 degrees C) and compared with those observed after treatment with noradrenaline (NA; 1.2 mg/kg/2 hr) under thermoneutral conditions (21 degrees C). 2. Both drugs abolished the thermogenic response to cold. 3. In the case of NA hyperthermia, only PRA was effective, i.e. the drug inhibited the thermal, metabolic and vasoconstricting actions of this amine. 4. Possible mechanisms, responsible for the thermoregulatory activity of both drugs are being discussed. PMID- 1511855 TI - Antinociception induced by intracerebroventricular or intrathecal administration of gentamicin in rats. AB - 1. The intrathecal (i.t.) administration of gentamicin (AD50 = 3.98 micrograms) produced marked and dose-dependent antinociception in rats, as assessed by the tail-flick test. A weaker effect was obtained following intracerebroventricular drug administration (AD50 = 50.12 micrograms). 2. A transitory but dose-dependent antagonism of the effect of i.t. gentamicin was obtained following i.t. administration of calcium chloride (4 and 8 micrograms). 3. The magnitude and duration of morphine antinociception (5 micrograms, i.t.) were enhanced by the previous (intraperitoneal) i.p. or i.t. administration of gentamicin. 4. These results indicate that gentamicin-induced antinociception may depend on its calcium-antagonist property and involves drug diffusion to a spinal site of action. PMID- 1511856 TI - Sex differences in physical dependence on pentobarbital in four inbred strains of rats. AB - 1. In Lewis (LEW), Fischer 344 (F344), Spontaneously hypertensive (SHR) and Wistar Kyoto (WKY) rats, pentobarbital (PB)-induced sleep time was much longer in female than in male rats. 2. At the time of awakening, brain levels of PB were significantly higher in the female F344 than in the male rats, but there was no sex differences in other strains. 3. Each strain of rats was treated with PB admixed food for 47 days. There were significant sex differences in mean drug intake of the SHR and LEW strains, but not the WKY and F344 strains during the final concentration. 4. Only female rats exhibited moderate to severe motor impairment by PB. 5. After PB treatment ended, various signs of PB withdrawal occurred in female, but not male, rats. These marked sex differences were observed in all four inbred strains. 6. The sex differences in physical dependence on PB may be due mainly to differences in rates of drug metabolism for the LEW, SHR and WKY rats, and to differences in CNS sensitivity for the F344 rats. PMID- 1511857 TI - Nicotine stimulates adrenergic terminals and inhibits contractions of mouse uterine horns. AB - 1. Nicotine (1-100 microM) stimulated both basal and electrically evoked release of 3H-norepinephrine and also caused a transient inhibition of contractions in an in vitro preparation of mouse uterine horns. 2. The inhibitory effect of nicotine on electrically evoked contractions was potentiated by aminophylline (89 micrograms/ml), and overcome by both propranolol (1 microM) and by omitting magnesium from the physiological solution. Acetylcholine (10 microM), in the presence of atropine (10 microM) was able to reproduce the inhibitory effect of nicotine. 3. These pharmacological findings suggest that the inhibitory action of nicotine on electrically evoked contractions in mouse uterus could be indirect, i.e. mediated through the action of this compound on presynaptic nicotine receptors located on adrenergic terminals. PMID- 1511858 TI - Acute cardiovascular effects of methyl methacrylate monomer: characterization and modification by cholinergic blockade, adrenergic stimulation and calcium chloride infusion. AB - 1. Methyl methacrylate monomer (MMA) given by i.v. infusion to anesthetized dogs caused a sustained hypotension, bradycardia, reduction of cardiac output and stroke volume, and increased peripheral resistance. 2. Epinephrine i.v. could reverse the hypotension but not the bradycardia; isoproterenol i.v. could reverse the bradycardia but not the hypotension. 3. Bilateral cervical vagotomy prevented bradycardia but not other cardiovascular effects of MMA, and prevented all respiratory effects except hypoxemia. 4. Calcium chloride i.v. reversed all circulatory changes except bradycardia; a combination of atropine and calcium reversed all cardiovascular changes from MMA. PMID- 1511859 TI - In vivo effects of indomethacin--I. Activity of antioxidant enzymes and lipid peroxidation. AB - 1. The in vivo effects of indomethacin on the activity of antioxidant enzymes and on lipid peroxidation in erythrocytes, liver and small intestines of rats were examined. 2. The activity of the enzymes studied increased or remained unchanged depending on the preparation and model used: treatment with "therapeutic" or "ulcerogenic" dose of indomethacin. 3. Indomethacin inhibited lipid peroxidation in the liver but not in the erythrocytes. 4. The results suggest that the stimulation of antioxidant enzymes, probably through in vivo formed metal complexes, is an alternative mechanism of the antiinflammatory action of indomethacin. PMID- 1511860 TI - Possibilities of the tolerance development to nipradilol and of the measurement of vascular glutathione content in isolated rat aorta. AB - 1. Nipradilol produced concentration-dependent relaxations of isolated rat aorta ring preparations under the contracture induced by norepinephrine or KCl, which were not significantly influenced by the previous incubation with nipradilol but significantly depressed by methylene blue. 2. The previous incubation with nipradilol did not influence the relaxant responses to nitroglycerin. 3. Five different methods for measurement of vascular glutathione content did not give the satisfiable results on the detected value of glutathione content in isolated rat aorta tissues. 4. Results indicate that nipradilol will not develop the tolerance to nipradilol itself and nitroglycerin. PMID- 1511861 TI - Interactions between the effects of endothelin-1, clonidine and yohimbine on electrically-induced contractions in rat vas deferens. AB - 1. The relationship between endothelin-1(ET-1)-induced effects on the contractile responses of epididymal portion of rat vas deferens elicited by field electrical stimulation (FES: 80 V, 1 msec, 0.1 Hz) and the effects of the alpha 2 adrenoceptor agonist clonidine and the alpha 2-adrenoceptor antagonist yohimbine were studied. 2. ET-1 (0.01 nM-0.1 microM) concentration-dependently increased the FES-induced contractions. 3. ET-1 (0.1 nM-0.1 microM) reversed the inhibitory effect of clonidine on the FES-evoked contractions whereas ET-1 applied before clonidine exerted a dual effect on the clonidine-induced inhibition of the FES evoked contractions. 4. The ET-1-induced enhancement of FES-induced contractions was potentiated in the presence of 1 microM yohimbine and was not observed at all in the presence of 10 microM yohimbine. Yohimbine, applied at concentrations of 1 and 10 microM exerted similar blocking effects on the alpha 1-adrenoceptor agonistic effects of phenylephrine. However, yohimbine at a concentration of 10 microM markedly potentiated the contractile effect of exogenous adenosine 5' triphosphate (ATP), 30 microM. Tetrodotoxin abolished this effect of yohimbine. 5. The results presented here suggest the existence of modulating interactions between the ET-1-evoked increase of FES-induced contractions of rat vas deferens and the alpha 2-adrenoceptor drugs clonidine and yohimbine. PMID- 1511862 TI - Structural study of the acute effect of Karwinskia humboldtiana on cerebral motor cortex, hippocampus, and caudate nucleus of the rat. AB - 1. Acute effects of Karwinskia humboldtiana (Kh) ingestion were studied in some cerebral motor regions. 2. In motor cortex, widening of Virchow-Robin spaces and hyperchromasia occurred throughout the study. 3. In CA1 region of hippocampus, hyperchromasia, swelling of cell nuclei and neuronal shrinkage; were observed at the various stages. 4. In caudate nucleus, cell shrinkage and nuclear swelling occurred throughout the study. 5. Cell death images were observed in all areas studied. 6. It is suggested that a toxic effect is produced by Kh fruit, and that tissue damages may be closely related to the motor non-paralytic disturbances observed after its ingestion. PMID- 1511864 TI - The effects of indomethacin on fibroblast chemotaxis. AB - 1. Boyden chambers were used to investigate the effects of indomethacin on fibroblast chemotaxis to a conditioned medium. 2. It was determined that indomethacin did not inhibit, but enhanced fibroblast chemotaxis at a concentration of 10(-4) (91%)-10(-6) M (79%). 3. No significant difference was found between controls and cells treated with 10(-8)-10(-10) M indomethacin. PMID- 1511863 TI - Effects of cirsiliol, a flavone isolated from Achillea fragrantissima, on rat isolated ileum. AB - 1. In concentrations from 10(-8) M to 3 x 10(-4) M, cirsiliol caused concentration-dependent relaxation of rat isolated ileum. 2. Phentolamine (10(-6) M) or phentolamine and propranolol (10(-6) M) had no significant effects on the concentration-effect curves or on the EC50 of cirsiliol on the ileum. 3. Cirsiliol shifted to the right the acetylcholine (Ach) concentration-effect curves on ileum and significantly inhibited the maximum contractions induced by Ach. 4. In Ca(2+)-free, depolarizing solution, cirsiliol shifted to the right the CaCl2 concentration-effect curves and inhibited the maximum contractions induced by CaCl2 on ileum. 5. Large concentrations (10(-4) M, 3 x 10(-4) M) of cirsiliol induced relaxation followed by contraction of the ileal segments incubated in Ca(2+)-free solution. 6. In Ca(2+)-free solution, cirsiliol (10(-4) M, 3 x 10(-4) M) caused concentration-dependent potentiation of the ileal contractions induced by 3 x 10(-3) M Ach when the latter was added 2-3 min after cirsiliol. When Ach was added 15-20 min after cirsiliol, the latter compound inhibited the Ach induced contractions. 7. These observations suggest that cirsiliol inhibits Ca2+ influx but stimulates Ca2+ release from intracellular stores. Furthermore, they suggest that cirsiliol utilizes the same Ca2+ source used by acetylcholine in Ca(2+)-free solution. PMID- 1511865 TI - The role of oriT in tra-dependent enhanced recombination between mini-F-lac-oriT and lambda plac5. AB - Recombination between F42lac and lambda plac5 is typically 20- to 50-fold more efficient than recombination between chromosomal lac and lambda plac5. This enhancement of recombination is recBCD-dependent and requires the expression of genes from the tra regulon of the F factor. Also required is oriT, the origin of F factor conjugational transfer, which must be located in-cis to the cellular copy of lac. In this study we show that enhanced recombination is not supported by an oriT point mutant that reduces oriT function in conjugation. We also present evidence that the activation of oriT for recombination enhancement involves the same strand-specific nick that is required for conjugal DNA transfer. Although it is thought that the role of oriT in recombination enhancement is related to the facilitated entry of RecBCD enzyme into the DNA duplex, we were unable to detect any double-strand breakage at oriT. PMID- 1511866 TI - Regulation of fitness in yeast overexpressing glycolytic enzymes: responses to heat shock and nitrogen starvation. AB - Current models based on the analysis of linear metabolic pathways at steady-state predict that large increases over wild type in the activity of one enzyme will not alter an organism's fitness. This prediction is tested at steps in a highly branched pathway under two conditions known to alter steady-state: heat shock and nitrogen starvation. Saccharomyces cerevisiae transformants overproducing 1 of 4 enzymes in glycolysis (hexokinase B, phosphoglucose isomerase, phosphofructokinase, or pyruvate kinase) were subjected to heat shock in both exponential and stationary phases of growth. In neither phase does enzyme overexpression alter heat shock sensitivity. When starved for nitrogen in acetate medium, transformants overproducing hexokinase, phosphoglucose isomerase, and phosphofructokinase sporulate at the same rate and with the same frequency as cells harbouring only the plasmid vector. Current models therefore correctly predict the relationship between activity and components of fitness for 3 of 4 enzymes. By contrast, cells overexpressing pyruvate kinase sporulate poorly. This defect is not observed among cells transformed with a plasmid containing a Tn5 disrupted copy of the PYK gene. These findings are consistent with reports that implicate the PYK locus in yeast cell cycle control and suggest that it may be challenging to model relations between fitness and activity for multifunctional proteins. PMID- 1511867 TI - Induced expression of a Drosophila hsp70 promoter-fusion transgene is reduced after repeated heat shocks. AB - Levels of transcripts produced by a heat shock protein 70 (hsp70)-antisense white transgene in Drosophila were measured after single and multiple heat shocks to determine whether the hsp70 promoter could produce sustained high levels of transgene transcripts. A single heat shock resulted in typical highly inducible levels of RNA, but the amount of antisense RNA was substantially reduced after multiple heat shocks. Endogenous hsp70 mRNA levels were also less abundant after multiple heat shocks as compared to a single heat shock. The hsp70 promoter is unsuitable for use in fusion gene constructs for long term expression studies where repeated heat shocks are required. PMID- 1511868 TI - The segmentation gene runt is needed to activate Sex-lethal, a gene that controls sex determination and dosage compensation in Drosophila. AB - In Drosophila, sex is determined by the relative number of X chromosomes to autosomal sets (X:A ratio). The amount of products from several X-linked genes, called sisterless elements, is used to indicate to Sex-lethal the relative number of X chromosomes present in the cell. In response to the X:A signal, Sex-lethal is activated in females but remains inactive in males, being responsible for the control of both sex determination and dosage compensation. Here we find that the X-linked segmentation gene runt plays a role in this process. Reduced function of runt results in female-specific lethality and sexual transformation of XX animals that are heterozygous for Sxl or sis loss-of-function mutations. These interactions are suppressed by SxlM1, a mutation that constitutively expresses female Sex-lethal functions, and occur at the time when the X:A signal determines Sex-lethal activity. Moreover, the presence of a loss-of-function runt mutation masculinizes triploid intersexes. On the other hand, runt duplications cause a reduction in male viability by ectopic activation of Sex-lethal. We conclude that runt is needed for the initial step of Sex-lethal activation, but does not have a major role as an X-counting element. PMID- 1511869 TI - Allelism tests of 15 dominant cataract mutations in mice. AB - Fifteen autosomal dominant mutations that cause cataract of lenses in mice were tested for allelism. The outcrosses of double mutants revealed three allelism groups, consisting of 5, 4 and 2 mutations as well as 4 mutations which segregated independently. The results indicated 7 different cataract loci in the sample of 15 mutations. The biomicroscopic examination of the eyes showed that phenotypically similar as well as very distinct cataract mutations can be alleles of the same gene. Conversely, phenotypically similar mutations were shown to be non-allelic. PMID- 1511870 TI - Population genetic aspects of deleterious cytoplasmic genomes and their effect on the evolution of sexual reproduction. AB - A conflict of interest may arise between intra-cellular genomes and their host cell. The example explicitly investigated is that of a 'selfish' mitochondrion which increases its own rate of replication at the cost of reduced metabolic activity which is deleterious to the host cell. The results apply to deleterious cytoplasmic agents in general, such as intracellular parasites. Numerical simulation suggests that selfish mitochondria are able to invade an isogamous sexual population and are capable of reducing its fitness to below 5% of that prior to their invasion. Their spread is enhanced by decreasing the number of mitotic divisions between meioses, and this may constitute a significant constraint on the evolution of lifecycles. The presence of such deleterious cytoplasmic agents favours a nuclear mutation whose expression prevents cytoplasm from the other gamete entering the zygote at fertilization, resulting in uniparental inheritance of cytoplasm. Such a mutation appears physiologically plausible and can increase in frequency despite its deleterious effect in halving the amount of cytoplasm in the zygote. It is suggested that these were the conditions under which anisogamy evolved. These results have implications for the evolution of sexual reproduction. Standard theory suggests there is no immediate cost of sex, a twofold cost being incurred later as anisogamy evolves. The analysis described here predicts a large, rapid reduction in fitness associated with isogamous sexual reproduction, due to the spread of deleterious cytoplasmic agents with fitness only subsequently rising to a maximum twofold cost as uniparental inheritance of cytoplasm and anisogamy evolve. PMID- 1511871 TI - In memoriam. Jean-Pierre Lecocq, 1947-1992. PMID- 1511872 TI - A vector for controlled, high-yield production of specifically mutated proteins in Escherichia coli: test of a putative cytidine-binding domain in Rho factor and its Thr16----Ala mutant. AB - A derivative of the plasmid vector, pET-3a [Rosenberg et al., Gene 56 (1987) 125 135], is described that contains the origin of replication from bacteriophage f1. This plasmid is well-suited for oligodeoxyribonucleotide mutagenesis and controlled production of mutant proteins from a single vector. Its utility is demonstrated by the preparation of a mutational alteration of Thr16----Ala (T16A) of the Escherichia coli transcription termination factor, Rho. The altered protein (T16A Rho) binds oligo(C)7 with the same affinity as wild-type (wt) Rho, thus indicating that Thr16 is not critical for binding cytidine residues in RNA, in spite of its being part of a sequence that is similar to a sequence in the CTP binding domain of aspartate transcarbamoylase. However, T16A Rho was less efficient in terminating transcription than was wt Rho and had a lowered kcat for ATP hydrolysis with cro RNA as co-factor. Thus, the change affects the coupling of ATP hydrolysis by Rho to actions on RNA that cause termination. PMID- 1511873 TI - A gene encoding a superoxide dismutase of the facultative intracellular bacterium Listeria monocytogenes. AB - A gene (lmsod) encoding superoxide dismutase (SOD; EC 1.15.1.1) of the facultative intracellular pathogen, Listeria monocytogenes, was cloned by functional complementation of an SOD-deficient Escherichia coli mutant. The nucleotide sequence was determined and the deduced amino acid (aa) sequence (202 aa) showed close similarity to manganese-containing SOD's from other organisms. Subunits of the recombinant L. monocytogenes SOD (re-SOD) and of both E. coli SODs formed enzymatically active hybrid enzymes in vivo. DNA/DNA-hybridization experiments showed that this type of recombinant re-sod gene is conserved within the genus Listeria. PMID- 1511874 TI - Cloning and sequence of a gene encoding the L7/L12 ribosomal protein equivalent of Streptomyces antibioticus. AB - A 50S ribosomal(r) protein from the vegetative mycelium of Streptomyces antibioticus, that is absent or modified in the spore 50S r-subunit, was purified by HPLC. Determination of its N terminus and comparison with amino acid sequence data bases indicated a strong homology with the L7/L12 r-protein from Streptomyces griseus. Screening of a cosmid library of S. antibioticus chromosomal DNA with a 20-mer oligodeoxyribonucleotide probe, corresponding to an internal region of the N terminus, allowed the isolation of two hybridizing clones. A 0.90-kb HindIII-BamHI fragment from one of these clones was sequenced and found to contain a 387-bp open reading frame. The deduced gene product shows clear homology with L7/L12 r-protein equivalent from different bacteria. PMID- 1511875 TI - Integration host factor facilitates repression of the put operon in Salmonella typhimurium. AB - Transcriptional regulation of the put operon is mediated by a unique mechanism involving autogenous regulation by the PutA protein, a membrane-associated dehydrogenase. The 420-bp put control region contains the putP and putA promoters, multiple operator sites, multiple catabolite repression protein binding sites, and several potential integration host factor (IHF)-binding sites (ihf). In this study, we show that IHF facilitates repression of the put operon in vivo, and IHF binds specifically to two ihf sites in the put control region in vitro. DNA gyrase mutants that alter the degree of chromosomal supercoiling do not affect put regulation, indicating that the effect of IHF on put expression is in this case independent of supercoiling. PMID- 1511876 TI - SDH1, the gene encoding the succinate dehydrogenase flavoprotein subunit from Saccharomyces cerevisiae. AB - We describe the isolation, sequence and construction of a disruption of the yeast SDH1 gene, encoding the flavoprotein subunit of succinate dehydrogenase. This is the first eukaryotic flavoprotein subunit-encoding gene to be fully sequenced. The deduced amino acid (aa) sequence is 50% identical to the Escherichia coli enzyme sequence. The yeast gene encodes an N-terminal extension of 45 aa relative to the E. coli sequence which may act as a mitochondrial targeting signal. Disruption of the gene results in the inability to respire, assayed as the inability to utilize the nonfermentable carbon source, glycerol. This is the expected phenotype for disruption of an essential component of the yeast citric acid cycle. PMID- 1511877 TI - GAL4 fusion vectors for expression in yeast or mammalian cells. AB - We describe two sets of vectors, one for yeast (pY1, pY2 and pY3) and one for mammalian cells (pM1, pM2, and pM3), that simplify the production of fusion proteins containing the DNA-binding domain of GAL4. This protein fragment, consisting of GAL4 amino acid (aa) residues 1-147, binds to a specific 17-bp nucleotide sequence, but is incapable of activating transcription unless fused to a protein that can contribute an activating function. Genetic strategies exploiting this property of GAL4 (aa 1-147) have been developed to characterize transcription factor functional domains, protein-protein interactions, and site specific proteolysis. The vectors we describe allow fusion to the C terminus of GAL4 (aa 1-147) in any reading frame, and thus facilitate these experimental strategies. PMID- 1511878 TI - A convenient cloning vector containing the GAL4 DNA-binding domain. AB - A DNA fragment encoding the yeast GAL4 DNA-binding domain (amino acids 3-147) was cloned into a convenient vector. This vector contains unique restriction sites at both the 5' and 3' ends and allows the generation of fusion proteins containing the GAL4 DNA-binding domain. These fusion proteins can be tested for their ability to activate transcription. PMID- 1511879 TI - An improved suicide vector for construction of chromosomal insertion mutations in bacteria. AB - We have constructed an R6K-based suicide vector (pJP5603) that requires a trans supply of the pir-encoded pi protein of plasmid R6K for replication. Therefore, efficient plasmid suicide results upon transfer to bacteria not harbouring pir. The 3.1-kb vector encodes kanamycin resistance and is mobilizable. When used in conjunction with a JM109 strain carrying pir, it has nine unique restriction sites available for alpha-complementation cloning. Vector functionality was demonstrated in Rhodobacter sphaeroides. PMID- 1511880 TI - Nucleotide sequence of the URA1 gene of Saccharomyces cerevisiae. AB - The complete nucleotide sequence of the URA1 gene encoding dihydroorotic acid dehydrogenase (DHOdehase) is presented. This enzyme catalyses the conversion of DHO to orotic acid and plays a major role in the pyrimidine pathway, as DHO is the effector of the positive control of the transcription of at least four genes, URA1, URA3, URA4 and URA10. Comparisons between the amino acid sequence of the yeast DHOdehase and sequences of DHOdehases previously isolated from Dictyostellum discoidum, Escherichia coli and Bacillus subtilis reveal no obvious homologies. PMID- 1511881 TI - Isolation and characterization of genetic expression and secretion signals from Enterococcus faecalis through the use of broad-host-range alpha-amylase probe vectors. AB - We have constructed two broad-host-range Gram+/Gram- probe vectors designed for the cloning of bacterial genetic expression and secretion signals. These vectors make use of a silent reporter gene encoding the mature alpha-amylase from Bacillus licheniformis whose reactivation can easily be monitored on iodine stained starch plates. Shotgun cloning of Enterococcus faecalis DNA fragments allowed recovery of several cassettes directing transcription, translation of the reporter gene and secretion of alpha-amylase. Sequence analysis revealed, in each case, the presence of a putative promoter, ribosome-binding site and signal peptide similar to those described in other Gram+ bacteria. PMID- 1511882 TI - A strategy to construct vector-free amylolytic strains through nondisruptive homologous recombination: application to Enterococcus faecalis. AB - In order to direct chromosomal integration of the alpha-amylase-encoding gene from Bacillus licheniformis (amyL) under the control of expression and secretion signals from Enterococcus faecalis, the chromosomal fragment (named AB) from the pGIP3124 plasmid [Hols et al., Gene 118 (1992) 21-30] was chosen and split into two fragments (A and B). A translation fusion between the A fragment and 'amyL, deleted of its expression and secretion signals, was made and this fusion was flanked with the AB fragment at its right end. The A::'amyL:AB integration module was cloned into a thermosensitive pE194 replicon (chloramphenicol resistant; CmR) and electro-transformed into E. faecalis OG1X. After an overnight culture in selective liquid medium, the offspring from the amylolytic transformants obtained was shown to yield CmR colonies with two distinct halo sizes on iodine-stained starch plates. Southern analysis clearly showed that the smaller halos corresponded to descendants in which the plasmid had integrated into the chromosome through homologous recombination. One such Amy+ integrant in the AB site was further cultured under nonselective conditions at 42 degrees C for about 20 generations, and the offspring was screened for Amy+/CmS clones. Such revertants were indeed found, and Southern analysis clearly showed that the vector matrix had been excised through homologous recombination between the redundant A sites, leaving the integrated amy gene intact. PMID- 1511883 TI - Addition of a dipeptide spacer significantly improves secretion of ovine trophoblast interferon in yeast. AB - Yeast has been analysed for its potential to secrete an ovine member of the type I interferon (IFN) family, trophoblastin (oTP-1). The processing potential of the yeast KEX2 gene product (KEX2p) was evaluated using gene oTP-1 fused to the pre pro sequence encoding the pre-pro peptide of the yeast alpha-factor precursor. High-level accumulation of nonprocessed (unmatured) recombinant oTP-1 (re-oTP-1) was observed in the medium. In order to short-circuit the limiting activity of KEX2p and to obtain a fully matured re-oTP-1, secretion was directed using a pre::oTP-1 fusion, relying only on signal peptidase-dependent processing. However, secretion of oTP-1 was impaired. High-level secretion was restored when the gene product contained a peptide spacer between oTP-1 and the signal peptidase cleavage site. The oTP-1 variant was shown to have an extended N terminus. An N-extended form was examined further and shown to have the correct size. Surprisingly, the variant retained its in vitro and in vivo biological activities. This system is likely to represent a general method for high-level secretion of type-I IFNs. PMID- 1511884 TI - Purification and characterization of the M.RsrI DNA methyltransferase from Escherichia coli. AB - The gene (rsrIM) encoding the RsrI DNA methyltransferase (M.RsrI) from Rhodobacter sphaeroides was cloned and expressed in Escherichia coli. Under the control of a bacteriophage T7 promoter, 2% of the total protein in a crude extract was M.RsrI. This level of expression represents an approximately 50-fold increase over that present in the natural host. Chromatography using DNA cellulose and the S-adenosylmethionine analogue, sinefungin, was useful in purifying the enzyme to homogeneity. The purification yielded 100 times more enzyme than was obtained from the same quantity of R. sphaeroides cell paste. M.RsrI deposits one methyl group per productive DNA-binding event, as does its functional but sequence-nonhomologous analogue, M.EcoRI. Unlike M.EcoRI, the R. sphaeroides enzyme is a dimer at micromolar concentrations. PMID- 1511885 TI - Sequence of the Kluyveromyces lactis beta-galactosidase: comparison with prokaryotic enzymes and secondary structure analysis. AB - The LAC4 gene encoding the beta-galactosidase (beta Gal) of the yeast, Kluyveromyces lactis, was cloned on a 7.2-kb fragment by complementation of a lacZ-deficient Escherichia coli strain. The nucleotide sequence of the structural gene, with 42 bp and 583 bp of the 5'- and 3'-flanking sequences, respectively, was determined. The deduced amino acid (aa) sequence of the K. lactis beta Gal predicts a 1025-aa polypeptide with a calculated M(r) of 117618 and reveals extended sequence homologies with all the published prokaryotic beta Gal sequences. This suggests that the eukaryotic beta Gal is closely related, evolutionarily and structurally, to the prokaryotic beta Gal's. In addition, sequence similarities were observed between the highly conserved N-terminal two thirds of the beta Gal and the entire length of the beta-glucuronidase (beta Glu) polypeptides, which suggests that beta Glu is clearly related, structurally and evolutionarily, to the N-terminal two-thirds of the beta Gal. The structural analysis of the beta Gal alignment, performed by mean secondary structure prediction, revealed that most of the invariant residues are located in turn or loop structures. The location of the invariant residues is discussed with respect to their accessibility and their possible involvement in the catalytic process. PMID- 1511886 TI - The isolation and characterization of the pyruvate kinase-encoding gene from the yeast Yarrowia lipolytica. AB - The dimorphic yeast, Yarrowia lipolytica, has been developed as a useful expression/secretion system for heterologous proteins such as chymosin and tissue plasminogen activator. To further develop this expression system, we have cloned the gene (PYK) encoding the highly expressed glycolytic enzyme, pyruvate kinase (PYK). Genomic clones were selected by their specific hybridization to synthetic oligodeoxyribonucleotide probes based on regions of the enzyme that were conserved through evolution. The clones identified by hybridization contained overlapping DNA inserts. We have confirmed the identity of the cloned gene based on two criteria: (1) the nucleotide sequence of the proposed PYK gene predicts a protein that is highly homologous to the corresponding Saccharomyces cerevisiae enzyme, and (2) PYK-specific activity was increased twofold when wild-type Y. lipolytica strains were transformed with the isolated DNA. Interestingly, we found that the open reading frame of the Y. lipolytica PYK gene was interrupted by an intron. This represents the first report of an intron in a Y. lipolytica gene. PMID- 1511887 TI - Characterization of a highly expressed lignin peroxidase-encoding gene from the basidiomycete Phanerochaete chrysosporium. AB - The genomic clone, LG2, encoding LiP2, the major lignin peroxidase (LiP) isozyme from Phanerochaete chrysosporium strain OGC101, was isolated and characterized. The 5'-untranslated region of LG2 contains sequences similar to CRE and XRE promoter elements. Comparison with its transcript indicates that eight introns, each less than 59 bp, interrupt the coding sequence. Comparison with genes encoding other LiP isozymes shows five related patterns of intron location, whose incidence coincides with described LiP structural subfamilies. Codon bias indices calculated for all known P. chrysosporium genes, including trpC and genes encoding LiP, MnP, and exo-cellobiohydrolase I, demonstrate that LG2 has the most biased codon usage. We conclude that subdivisions of the LiP family may be based on intron location in the encoding genes, and that ranking of isozyme production levels can be estimated by the extent of bias in codon usage in the cognate gene. PMID- 1511888 TI - Development of a prokaryotic expression vector that exploits dicistronic gene organization. AB - For unknown reasons, levels of expression of foreign genes inserted into expression vectors in Escherichia coli have frequently been undetectable. The most critical step in the successful production of foreign proteins seems to be the initiation of translation. Since most prokaryotic genes are transcribed in a polycistronic form, we have devised a new prokaryotic expression system utilizing dicistronic gene organization. Downstream from a strong promoter and the gene encoding glutathione S-transferase from Schistosoma japonicum, various foreign genes were connected via a ribosome-binding site, a stop codon and a start codon. The VH domain of an immunoglobulin fused to the alpha subunit of tryptophan synthase, FK506-binding protein, cyclophilin, and a domain of a major histocompatibility complex antigen were successfully produced in E. coli as discrete polypeptides by this method. PMID- 1511889 TI - The yptV1 gene encodes a small G-protein in the green alga Volvox carteri: gene structure and properties of the gene product. AB - Small G-proteins encoded by ras-like genes are ubiquitous in eukaryotic cells. These G-proteins are believed to play a role in central processes, such as signal transduction, cell differentiation and membrane vesicle transport. By screening genomic and cDNA libraries of the colonial alga, Volvox carteri f. nagariensis, with ypt DNA probes from Zea mays, we have identified the first member of a ypt gene family, yptV1, within a green alga. The 1538-bp yptV1 gene of V. carteri consists of nine exons and eight introns and has three potential polyadenylation sites 210, 420 and 500 bp downstream from the UGA stop codon. The derived 203 amino-acid polypeptide, YptV1, exhibits 81% similarity with Ypt1 from mouse, with the corresponding genes sharing four identical intron positions. Recombinant YptV1 (reYptV1) produced in Escherichia coli retains the ability to bind GTP after SDS-PAGE and immobilization on nitrocellulose. Immunological studies using polyclonal antibodies against reYptV1 indicate that the protein is present in the membrane fraction of a V. carteri extract and is expressed throughout the whole life-cycle of the alga. Similar to other Ras-like proteins, YptV1 contains two conserved C-terminal cysteine residues suggesting post-translational modification(s), such as isoprenylation or palmitoylation, required for membrane anchoring. The presumptive role of YptV1 in cytoplasmic vesicle transport is briefly discussed. PMID- 1511890 TI - Sequence analysis of the indirect flight muscle actin-encoding gene of Drosophila simulans. AB - A genomic clone of the Drosophila simulans indirect flight muscle actin-encoding gene (Act88F) has been isolated, and the sequence of a 3358-nucleotide segment corresponding to the Drosophila melanogaster Act88F transcription unit is presented. The ACt88F homologs in these two sibling species encode identical proteins and the general genomic organization of the Act88F locus is highly conserved, including the location of the transcription start point, and the size and position of intron/exon junctions. Substitutions within the 5' flanking region, however, are clearly nonuniform and the regions of lowest divergence coincide with regions that have been implicated in transcript accumulation and the regulation of tissue-specific expression. Silent substitutions within the coding regions have been compared to five other gene homologs in these sibling species. The rate of silent substitution at these loci varies more than threefold, suggesting selection at the codon level. PMID- 1511891 TI - Identification of a genomic DNA fragment containing the Drosophila melanogaster ovarian tumor gene (otu) and localization of regions governing its expression. AB - We have identified a genomic DNA fragment which restores fertility to mutants of the ovarian tumor locus (otu) of Drosophila melanogaster. Germ-line transformants bearing this fragment express otu mRNA with the same tissue specificity as, and at levels comparable to, the wild-type otu gene. Transcription from the otu promoter, P(otu), which lacks a TATA element, appears to be initiated at multiple transcription start points (tsp) within an 80-bp region. Deletion of sequences upstream of the tsp indicates that a region between nucleotides -190 and -310 is required for proper expression from the otu gene. A DNA fragment containing 452 bp upstream and 126 bp downstream from the tsp is able to direct expression of the Escherichia coli lacZ gene in the germ cells of the ovary and testis, indicating that cis-acting regulatory elements governing these expression patterns are located in a 578-bp region surrounding the multiple tsp. PMID- 1511892 TI - Ependymins from the cerebrospinal fluid of salmonid fish: gene structure and molecular characterization. AB - So far, ependymins (Epds) have been sequenced only from cypriniform fish, and in the past all attempts have failed to characterize, on a molecular level, homologous Epd proteins in higher vertebrates. Therefore, rainbow trout (Oncorhynchus mykiss) Epds, which represent the predominant proteins of the cerebrospinal fluid, have been N-terminally sequenced and the encoding cDNA subsequently cloned using the polymerase chain reaction. Surprisingly, only 40 42% of the amino acids are identical with the corresponding sequences from goldfish (Carassius auratus), and no convincing immunological cross-reactivity is observed with an antiserum raised against purified Epds from C. auratus. O. mykiss possesses two highly homologous genes encoding Epds (Om-I, Om-II), a feature typical of a quasi-tetraploid species. Western analysis, using two specific antibodies against Epds from O. mykiss, revealed a variety of different glycosylation variants. In contrast to C. auratus, Epds from O. mykiss probably do not form disulfide-linked dimers. The structure of one Epd gene and its flanking regions have been determined for the Atlantic salmon (Salmo salar). Six exons were deduced by comparison with the corresponding cDNA sequence from O. mykiss (almost 98% homology with Om-II). PMID- 1511893 TI - Rainbow trout mitochondrial DNA: sequence and structural characteristics of the non-coding control region and flanking tRNA genes. AB - We have determined the sequence of the 1003-bp control region (also referred to as the 'displacement-loop region') and flanking tRNA genes in the mitochondrial DNA (mtDNA) of the rainbow trout, Oncorhynchus mykiss. This region has the same overall structure (i.e., trnT-trnP-control region-trnF) as in mammalian and amphibian (Xenopus laevis) mitochondrial (mt)DNAs. The trout control region contains apparent homologues of the conserved sequence blocks (CSB) and termination-associated sequences identified in all other vertebrate mtDNA control regions; however, it is distinguished by having an imperfect direct repeat (68/73 bp; 77% positional identity) in the right domain (proximal to the phenylalanine tRNA gene), downstream from CSB-3 in the direction of heavy-strand transcription. Within the control region, rainbow trout mtDNA shares considerable sequence similarity with the mtDNAs of Atlantic cod, Gadus morhua (Johansen et al., Nucleic Acids Res. 18 (1990) 411-419] and white sturgeon, Acipenser transmontanus (Buroker et al., Genetics 124 (1990) 157-163). The highest level of identity in pairwise comparisons is 60-70% over about 80 bp in the right domain (encompassing CSB-2 and CSB-3). About 270 bp comprising the central domain of the control region (encompassing a polypyrimidine tract) are more moderately conserved (55 60% identity in pairwise comparisons), while the left domain is highly divergent. Comparison of five trout mitochondrial tRNA sequences with their human and X. laevis homologues emphasizes the strong A+T substitution bias shown by the human sequences. PMID- 1511894 TI - Characterization of the murine thymidine kinase-encoding gene and analysis of transcription start point heterogeneity. AB - We have determined the molecular organization and transcription start points (tsp) for the murine gene (TK) encoding thymidine kinase. The exon/intron structure and sequences present at the splice junctions of the mammalian TK genes have been highly conserved; however, the promoter sequences of these genes have diverged widely. Both the human and Chinese hamster TK promoter regions contain CCAAT and TATA consensus motifs, whereas the mouse promoter has neither element. This difference between species is reflected in that, unlike the hamster and human TK genes, transcription initiates from numerous specific tsp within a 100 bp region in the mouse TK gene. The complex pattern of tsp seen in the endogenous gene was not maintained in transfected cell lines containing TK promoter::beta globin (HBB) fusions. Transcription from the murine TK:HBB fusion genes initiated from a small number of tsp that were clustered downstream from the ATG in hybrids containing TK coding sequences, and in the HBB 5' UTR in hybrids that did not. Few or no specific tsp were detected from the upstream sites used in the endogenous mouse TK gene. PMID- 1511895 TI - Genomic organization and tissue expression of the murine gene encoding the protein beta-aspartate methyltransferase. AB - Two overlapping clones containing the entire 684-nucleotide (nt) sequence encoding murine protein beta-aspartate methyltransferase (EC 2.1.1.77) were isolated from a genomic library. Partial nt sequence analysis of the two clones revealed that the protein carboxyl methyltransferase (PCMT)-encoding sequence is distributed among seven exons, ranging from 32 to 339 bp in length, within 25 kb of genomic DNA. Three exons correspond to regions of primary structure which are strongly conserved among a number of eukaryotic and prokaryotic enzymes which utilize S-adenosylmethionine (AdoMet) and S-adenosylhomocysteine (AdoHcy). The 5' flanking region of the PCMT-encoding gene (PCMT) contains an 800-bp G+C-rich region with potential binding sites for transcription factor ETF, but lacks a TATA box and binding sites for other known transcription factors. Multiple PCMT mRNAs were detected on Northern blots of RNA extracted from murine brain, testis, liver and kidney. The overall abundance of PCMT mRNAs in each tissue paralleled the measured specific activity of the PCMT. Comparison of the genomic sequence information with the 3'-untranslated regions (UTRs) of two cDNA clones from a murine testis library indicated that PCMT mRNA precursors undergo alternative splicing. The structure and widespread expression of PCMT are characteristics of vertebrate housekeeping genes. PMID- 1511896 TI - Insulin increases transcription of rat gene 33 through cis-acting elements in 5' flanking DNA. AB - Gene 33 is a multihormonally-regulated rat gene whose transcription is rapidly and markedly enhanced by insulin in liver and cultured hepatoma cells. To examine the mechanism by which insulin regulates transcription, we have constructed chimeric plasmids in which expression of the bacterial cat gene, encoding chloramphenicol acetyltransferase (CAT), is governed by gene 33 promoter elements and contiguous sequences in DNA flanking the transcription start point (tsp). When transfected into H4IIE hepatoma cells, these constructs gave rise to stably transformed cell lines producing the bacterial CAT enzyme. This expression was increased by insulin treatment in a fashion resembling the effect of this hormone on transcription of the native gene. In vitro transcription assays in nuclear extracts also revealed increased transcription of the chimeric plasmids when the extracts were prepared from insulin-treated rat hepatoma cells. The results demonstrate that induction by insulin is mediated by cis-acting nucleotide sequences located between bp -480 to +27 relative to the tsp. PMID- 1511897 TI - The carbamyl phosphate synthetase promoter contains multiple binding sites for C/EBP-related proteins. AB - The promoter of the gene (CPS) encoding rat carbamyl phosphate synthetase I has been mapped 5' to a segment of about 525 nucleotides upstream from the transcription start point and, when analyzed in liver nuclear extracts, contained six well-defined protein-recognition elements, designated CPS sites I-VI. All six elements were recognized, with varying affinities, by CAAT and enhancer-binding protein (C/EBP alpha) produced in bacteria. Oligodeoxyribonucleotides corresponding to CPS site II or to the C/EBP alpha-recognition element of the ALB promoter, site D, competed with the six CPS-promoter elements in footprinting assays. However, mutagenesis of the C/EBP alpha-recognition element, 5'-GTTGCAAC, at the core of site II was sufficient to abolish transactivation of the CPS promoter by C/EBP alpha in co-transfected HepG2 cells. These findings indicate that the CPS promoter contains multiple recognition elements for factors with DNA binding specificities similar to C/EBP proteins. Activation by C/EBP alpha, however, requires promoter site II. PMID- 1511898 TI - Production of mature bovine pancreatic ribonuclease in Escherichia coli. AB - The coding sequence for the bovine pancreatic ribonuclease (RNase) precursor has been cloned and produced in Escherichia coli using the polymerase chain reaction (PCR) technique. A PCR amplification has been carried out utilizing as template the recombinant plasmid, pQR138, which contains the coding sequence for the RNase precursor, and primers that allow for the addition of new sequences at the 5' and 3' ends of the coding sequence. The resultant fragment contains two coding sequences, one for a hexapeptide and the other for pre-RNase. This fragment has been cloned into the expression vector, pKK223.3, under the control of the tac promoter, to form a two-cistron vector. Upon induction with IPTG, E. coli cells harboring this construct generate a bicistronic mRNA which upon translation produces a hexapeptide and pre-RNase. The RNase precursor is efficiently translocated into the periplasmic space of E. coli. Upon translocation, the signal sequence is removed generating mature RNase. Formation of the disulfide bridges in RNase is facilitated by the oxidative environment of the periplasm and a fully active protein is obtained. RNase produced in E. coli has been purified to homogeneity by cation-exchange chromatography, and the removal of the signal sequence has been verified by N-terminal sequencing. The total process from inoculation of media to obtaining pure and fully active recombinant RNase is achieved in 48 h. PMID- 1511899 TI - Transcription of the chicken anemia virus (CAV) genome and synthesis of its 52 kDa protein. AB - This paper describes the expression of the chicken anemia virus (CAV) genome, a recently characterized single-stranded circular-DNA virus of a new type [Noteborn et al., J. Virol. 65 (1991) 3131-3139]. The major transcript from the CAV genome is an unspliced mRNA of about 2100 nucleotides (nt). Its transcription start point and poly(A)-addition site are located at nt 354 and 2317 of the CAV sequence, respectively. In vitro translation experiments provide evidence that the major CAV open reading frame encodes a 52-kDa protein by using the fifth AUG as a start codon of the unspliced CAV mRNA. PMID- 1511900 TI - The Drosophila melanogaster ribosomal protein L17A-encoding gene. AB - The structure and sequence of the gene encoding the Drosophila melanogaster homolog of the human and yeast large-subunit ribosomal protein L17A (rpL17A) is presented. The deduced amino acid (aa) sequence of 140 residues exhibits 87% and 77% identity to that of the human (140 aa) and yeast (137 aa) rpL17As, respectively. The D. melanogaster rpL17A gene is single copy and maps at 58F6 59A3, a chromosome region encompassing a previously characterized Minute locus, M(2)I. Despite this extensive homology in their protein products, the D. melanogaster and yeast rpL17A genes display different exon-intron structures, with the first D. melanogaster intron mapping within the 5'-untranslated mRNA leader. The rpL17A gene gives rise to a single 600-nucleotide transcript present throughout development, and is located close to another similarly expressed gene. The 5' end of the D. melanogaster rpL17A mRNA contains a polypyrimidine tract displayed by several mammalian rp genes and involved in translational control of their expression. PMID- 1511901 TI - Cloning and sequence of a functionally active cDNA encoding the mouse ubiquitin activating enzyme E1. AB - A cDNA encoding the ubiquitin-activating enzyme, E1, was isolated from the mouse mammary carcinoma cell line, FM3A, and shown to complement mutant mouse cells deficient in the enzyme. The 3495-bp cDNA encodes 1058 amino acids (aa), and shares extensive homology with the human E1 enzyme at both the nucleotide and aa sequence levels. PMID- 1511902 TI - Factors interacting with the rat carbamyl phosphate synthetase promoter in expressing and nonexpressing tissues. AB - The proximal promoter of the rat carbamyl phosphate synthetase-encoding gene (CPS) contains at least six potential cis-acting regulatory elements (sites I VI), as judged by DNase I footprint analysis using rat liver nuclear extracts; all six regions bind proteins with DNA recognition properties similar to those of CAAT and enhancer-binding protein alpha (C/EBP alpha) [Lagace et al., Gene 118 (1992) 231-238]. In contrast, nuclear extracts from kidney, brain and spleen contain proteins that recognize CPS promoter sites II, V and VI, but not sites I, III and IV. Mutation of the octameric sequence (5'-GTTGCAAC) within site II, which is a recognition element for C/EBP alpha, abolished binding of nuclear proteins to site II oligodeoxyribonucleotides (oligos) in all tissues. As well, the site II mutation reduced the level of in vitro transcription from the CPS promoter by about 50% in liver and spleen nuclear extracts, but had a negligible effect in brain and kidney extracts. The fact that promoter activity was observed in extracts of tissues that do not express the endogenous CPS gene (i.e., brain, kidney and spleen) indicates that these tissues, nevertheless, contain factors with the potential to activate transcription through a limited number of CPS promoter elements. Tissue-specific regulation, therefore, must involve steps to prevent these factors from acting on the endogenous CPS promoter in situ. PMID- 1511903 TI - Sequence of a rat TIS11 cDNA, an immediate early gene induced by growth factors and phorbol esters. AB - We report here the nucleotide sequence of a rat TIS11 cDNA, an immediate early gene, induced by nerve growth factor and epidermal growth factor, by 12-O tetradecanoyl phorbol-13-acetate, and other stimuli in PC12 pheochromocytoma cells. The deduced protein consists of 320 amino acid residues with two tandem repeats of a putative Zn(2+)-finger motif. PMID- 1511904 TI - Plasmid pLTRpoly: a versatile high-efficiency mammalian expression vector. AB - Plasmid pLTRpoly is an expression vector enabling high-level expression of introduced genes in a variety of cell types. A large multiple cloning site (MCS) and the availability of the full-length nucleotide sequence facilitate the generation of constructs using this vector. Here, constructs made with pLTRpoly have been tested in NIH3T3 mouse fibroblasts. PMID- 1511905 TI - Sequence of a cDNA clone encoding a rat Reg-2 protein. AB - We report here the nucleotide sequence of a rat cDNA clone encoding a protein homologous to the Reg (regenerating) protein. The encoded protein, designated Reg 2, shows 60%, 78% and 61% similarities with the reported amino acid sequences of the rat, bovine and human proteins, respectively. PMID- 1511906 TI - Repeat sequences in the gene encoding the human D4 dopamine receptor. AB - The gene encoding the human D4 dopamine receptor has evolved by gaining at least five internal repeats which are located within exons 3 and 4, and in the intervening intron 3 sequence. The amino acid sequence in the cytoplasmic loop of the receptor, involved in G protein coupling, has been altered by these gene changes. PMID- 1511908 TI - Healthcare reform: a scorecard. PMID- 1511907 TI - Cloning of a cDNA encoding a receptor related to the formyl peptide receptor of human neutrophils. AB - We cloned a cDNA (RFP) encoding a receptor (RFP) related (70% overall nucleotide homology) to the formyl peptide receptor of human neutrophils (hFPR). RFP is a seven-transmembrane-domain receptor and its distribution is limited to myeloid cells. Domain sequence comparison with hFPR reveals highly conserved regions and provides clues to putative domains involved in ligand binding and receptor desensitization. PMID- 1511909 TI - Health care for all: a crisis of cost and access. A roundtable discussion: Part 1. AB - Primary care physicians are feeling the impact of a healthcare system in crisis. Many Americans have no health insurance, paperwork is consuming more and more of physicians' time, and concerns about controlling costs seem to overshadow the value of medical decision-making. Medicare protects the elderly, but low reimbursement fees act as a disincentive to accepting them as patients. Although there is a general consensus that reforms are needed, there are many different opinions on how this should be achieved. In this first part of a three-part roundtable discussion, seven experts in the fields of aging, medicine, and government discuss flaws in our current system and factors that are interfering with reform. PMID- 1511910 TI - Physicians for a National Health Program: a radical proposal? PMID- 1511911 TI - Confessions of a new geriatrician. PMID- 1511912 TI - Potential for therapeutic gain from combined-modality treatment. PMID- 1511913 TI - Chemoradiation for gastrointestinal cancer. PMID- 1511914 TI - Anal canal carcinomas. PMID- 1511915 TI - Radio-chemotherapy for invasive carcinoma of the bladder. PMID- 1511916 TI - Combined chemotherapy and radiotherapy for advanced-stage carcinomas of the cervix. PMID- 1511917 TI - Interactions of chemotherapeutic agents and radiation. PMID- 1511918 TI - Paediatric oncology: the optimal model for evaluating radiation-chemotherapy interactions. PMID- 1511919 TI - Combined-modality therapy for the treatment of Hodgkin's disease. PMID- 1511920 TI - Concomitant infusion chemotherapy and irradiation. PMID- 1511921 TI - Experimental studies on schedule dependence in the treatment of cancer with combinations of chemotherapy and radiotherapy. PMID- 1511923 TI - Concomitant chemoradiotherapy as investigational therapy for locoregionally advanced head and neck cancer. PMID- 1511922 TI - Effects of chemotherapy and irradiation on normal tissues. PMID- 1511924 TI - Interaction of chemotherapy and radiation in the treatment of nonmetastatic breast cancer. PMID- 1511925 TI - [Industrialization and its impact on workers' health]. PMID- 1511926 TI - [Hygienic and ecological standardization: methodologic approaches and ways of integration]. PMID- 1511927 TI - [Hygienic problems of health protection of the rising generation]. PMID- 1511928 TI - [Possibilities of primary prevention of ischemic heart disease]. PMID- 1511929 TI - [Problems of ecology-caused occupational diseases of the respiratory organs]. PMID- 1511931 TI - [Environmental health at present]. PMID- 1511930 TI - [Sanitary-hygienic safety of troops participating in cleaning-up of consequences of disasters]. PMID- 1511932 TI - [Tasks of training public health physicians at present]. PMID- 1511933 TI - [Improving the quality of professional training of public health physicians and epidemiologists]. PMID- 1511934 TI - [Summing up the activities of the scientific society of public health physicians]. PMID- 1511935 TI - Recommendations of the DNA Commission of the International Society for Forensic Haemogenetics relating to the use of PCR-based polymorphisms. PMID- 1511936 TI - Detection of polymorphisms of human DNA after polymerase chain reaction by miniaturized SDS-PAGE. AB - PCR followed by SDS-PAGE in miniaturized non-denaturing gels permits in some cases the identification of single base pair substitutions in small DNA fragments and therefore, the study of human DNA polymorphisms. The usefulness of the system in forensic science is investigated by typing the HLA-DQA1 locus and the VNTR recognized with the probe pMCT118 (locus D1S80) and it shows to be advantageous over previously published methods for typing the MCT118 system, whereas in HLA DQA1 typing for forensic casework, both dot-blot with ASO probes and this method could be complementary. PMID- 1511937 TI - Complement component C3a or C3a desArg as a new marker for estimation of local vital reactions in incised skin wounds. AB - The anaphylatoxin C3a or its desArg form (C3a/desArg) generated during complement activation could be detected in the vicinity of incised skin wounds of guinea pigs using immunoblotting methods. The C3a/desArg peptides were detectable immediately after injury in local sites up to 3 mm from the wound edge. In subsequent determinations of up to at least 3-day-old antemortem wounds, the maximum concentration of these peptides was largely localized up to 6 mm from the wound edge at 2 h after injury. In postmortem wounds, however, these peptides were undetectable. When they were released in antemortem wounded tissues they could be detected up to 1 day at 22 degrees C after death. These results suggest that the detection of C3a/desArg in wounds using immunoblotting methods can be useful for distinguishing ante- from postmortem wounds. PMID- 1511939 TI - HLA-DQA1 allele and genotype frequencies in a northern Italian population. AB - HLA-DQA1 typing of 227 randomly selected Northern Italian people by the use of polymerase chain reaction are reported. The combined use of commercial Amplitype HLA-DQalpha system and four sequence-specific oligonucleotide probes allows the definition of 8 alleles and 36 genotypes, arranged according to World Health Organisation nomenclature. Seven of these genotypes are not observed among the analyzed samples. Allele frequencies range from 1.5 to 35.7% and genotype observations do not deviate significantly from Hardy-Weinberg equilibrium; observed heterozygosity is 0.8238 with an allelic diversity value of 0.79 and the power of discrimination is 0.925. Our Italian population sample shows differences from other Caucasian samples both for allele and genotype frequencies. This locus typing for the 8 defined alleles provides a rapid and sensitive method in individual identification and paternity investigation. PMID- 1511938 TI - Biostatistical basis of individualization and segregation analysis using the multilocus DNA probe MZ 1.3: results of a collaborative study. AB - A collaborative study using the multilocus minisatellite DNA probe MZ 1.3 was carried out to investigate segregation information, mutation rate, DNA fragment frequencies as well as band sharing characteristics. The fingerprint patterns of 393 children as well as 694 unrelated individuals were analysed after digestion of DNA with the restriction enzyme HinfI. A mutation rate of 1% per meiosis or 0.04% per band was found with a mean number of 26 bands/individual. It was shown that maternal and paternal fragments are inherited in equal proportions. Population frequencies of restriction fragments demonstrated a distribution with increasing frequencies in the small fragment size range below 10 kb as well as the absence of very common or very rare fragments. Our data can be used to calculate simple exclusion probabilities based on the number of non-maternal bands in the child. PMID- 1511940 TI - Drug abuse in western Denmark during the eighties. I. Drugs of abuse. AB - A description is given of the availability and quality of drugs seized in the Danish illicit drug market during the eighties. Cannabis was the most prevalent illegal drug throughout the decade. Seizures of heroin predominated among the 'hard' illegal drugs until 1987 but during the late eighties a significant increase in amphetamine seizures was observed. Most of the cocaine was seized in transit, apparently not meant for the Danish market. Medical drugs, particularly benzodiazepines and the synthetic opiates methadone and ketobemidone, comprised an increasing part of the illegal drug market during the period. No seizures of designer drugs were seen. The street level purities of both heroin and amphetamine were, on average, 30-40%. PMID- 1511941 TI - Drug abuse in western Denmark during the eighties. II. Fatal poisonings among drug abusers. AB - Cases of fatal poisoning among drug addicts (n = 246) and abusers of medical drugs (n = 138) are discussed on the basis of the availability of illicit and medical drugs during the eighties. Propoxyphene was frequently the cause of death among both drug addicts and abusers of medical drugs. Deaths caused by analgesics and psychoactive drugs, mainly barbiturates and antidepressants, predominated among abusers of medical drugs. During the late eighties the number of deaths caused by barbiturates and propoxyphene declined as a result of changes in the distribution regulations for both drugs. Heroin/morphine accounted for only one third of the poisonings in drug addicts. No trends concerning the prevalence of deaths caused by these drugs were observed throughout the decade. The number of deaths caused by the synthetic opiates methadone and ketobemidone, however, increased during the late eighties, probably due to an increased availability of these drugs in the illicit drug market. Alcohol was detected in half of all the poisoning cases and benzodiazepines in one-third. PMID- 1511942 TI - Prevalence of HIV-1 antibodies in drug addicts autopsied at the University Institute of Forensic Pathology in Copenhagen 1988-1991. AB - In the period 1988-1991 the HIV-1 antibody test was performed in a total of 389 autopsied drug addicts. The HIV-1 incidence rose from 6% in 1988 to 14% in 1990 and 14% in 1991. There was no significant difference between the cumulated incidence in males and females. The HIV-1-positive addicts were compared to the HIV-1 negative addicts as regards mean age, duration of abuse, residence and cause and manner of death. Except for residence, where significantly more HIV-1 positive than negative addicts lived in Copenhagen, there were no significant differences between the two groups. In about one-third of the HIV-1-positive cases, equal both for males and females, the HIV-1-positivity was not known beforehand. The results are discussed in relation to the findings in other countries and to the findings in selected groups of living addicts in Copenhagen. It is concluded, that the diagnosis of HIV-1 infection in autopsied drug addicts is important from epidemiologic and hygienic points of view. PMID- 1511943 TI - Women, homicide and alcohol in Cape Town, South Africa. AB - Little is known about the complex circumstances culminating in the homicidal death of a woman. The records of 248 female homicides and suicides admitted to the Salt River State Mortuary between January 1990 and July 1991 were reviewed with specific attention to mode of death and blood alcohol concentration (BAC). Female homicide levels reflected the intensity of violence in specific residential areas. White females were far more likely to die a suicidal, as opposed to homicidal, death (Odds Ratio = 31.94; 95% Confidence Interval, 11.63 90.24). Blunt homicide predominated amongst White females, who were substantially older than the Coloured and African subjects. A BAC greater than 0.1 g per 100 ml was found in 56% of all female homicides studied. An association was found between increasing BAC and sharp homicide amongst women. A high BAC may represent a self-destructive element in a risk-taking situation amongst female homicide victims. PMID- 1511944 TI - [Psychiatry and psychoanalysis--Eugen Bleuler's "dementia praecox or group of schizophrenias" (1911)]. AB - Unlike many psychiatrists around 1900, Eugen Bleuler had a friendly, even partly affirmative attitude towards psychoanalysis. In his famous book "Dementia Praecox or Group of Schizophrenias" (1911) he emphasized the influence of psychoanalysis on his theory about schizophrenia. In this article we describe Bleuler's fundamental thoughts on psychology and psychotherapy in order to look for a special disposition to accept psychoanalysis. Psychoanalysis seemed to him to be one of the most promising attempts to develop a systematic psychotherapy founded on a scientific psychology. In particular, Freud's hypothesis about the wish fulfilling character of dreams influenced Bleuler's understanding of delusion and other symptoms of schizophrenia. PMID- 1511945 TI - [The Leonhard classification of endogenous psychoses--initial biological findings and differential therapeutic considerations]. AB - Current systems of classification of endogenous psychoses, the APA's Diagnostic and Statistical Manual and the International Classification of Diseases in particular, aim at a synthesis of Kraepelin's prognosis-orientated diagnostic scheme with the symptomatological approach as established by Eugen Bleuler and Kurt Schneider. The restriction to few diagnostic entities has remained unchanged to the present day and appeared at first to be confirmed and validated by modern pharmaco-psychiatry. Kraepelin's dichotomy has failed to make a major contribution to the etiologic clarification of endogenous psychoses. New diagnostic concepts beyond those currently applied in clinical psychiatry and biological psychiatric research must therefore be considered and should lead towards a more differentiated approach to psycho-pathological phenomena. Karl Leonhard's classification of endogenous psychoses which rests upon the pioneer work of Carl Wernicke and Karl Kleist is part of a tradition in psychopathology emphasizing the interface of biology and psychopathology. It might provide a basis for future empirical research in biological psychiatry and pharmacopsychiatry. PMID- 1511946 TI - [Xanthogranuloma of the choroid plexus of the lateral ventricle (case report)]. AB - We report on a case of a 59-year old man. During work he died suddenly and unexpectedly. Autopsy revealed myocardial infarction as cause of death. We also found symmetrical granulomatous proliferations proceeding from choroid plexuses of the lateral ventricles of the brain. Results of histological and chemical investigation proved the tumours to be xanthogranulomas. Despite their unusual size they did not cause any neurological or psychiatric symptoms. The patient had been known to have hypercholesterinemia for years. PMID- 1511947 TI - [What are the psychiatrist's expectations from nuclear magnetic resonance tomography and spectroscopy?]. AB - Magnetic resonance imaging (MRI) of the brain has several advantages over CAT scans (CT). MRI will gradually replace CAT-scans for most of the diagnostic examinations in psychiatry. MRI has an advantage in detecting discrete lesions of the brain. This is demonstrated by a review of MRI studies with schizophrenic and alcohol dependent patients. Magnetic resonance spectroscopy (MRS) is suitable for the in-vivo investigation of brain functions. MRS might provide the greatest advantage for future research in psychiatry. This is demonstrated by different studies, where the concentration and the kinetics of psychopharmacological agents in the brain were measured in-vivo. PMID- 1511948 TI - [Present status of open-heart surgery in neonates]. PMID- 1511949 TI - [Secretion of insulin and pancreatic polypeptide from the isolated perfused ventral and dorsal portions of the rat pancreas]. AB - The stimulation of the secretion of insulin and pancreatic polypeptide (PP) by carbachol, three different neuropeptides (gastrin-releasing peptide (GRP), vasoactive intestinal polypeptide (VIP) and neuromedin C (NC)), and glucose was investigated using the isolated perfused ventral part of the rat pancreas, with or without atropine. We used a specific radioimmunoassay for the secretion of rat PP. In addition, we studied the secretion of insulin and PP from the dorsal part of the rat pancreas in response to GRP and carbachol. The secretion of insulin and PP in response to carbachol and GRP were dose-dependent in range of 10(-9) M to 10(-6) M. The responses of insulin and PP to carbachol (10(-7) M) were biphasic, and were abolished by atropine (10(-5) M). Those in response to GRP (10(-7) M) were transient, monophasic and not inhibited by atropine (10(-5) M). VIP (10(-7) M) stimulated PP slightly and insulin obviously. Such secretion was not influenced by atropine (10(-5) M). Neuromedin C showed a bioactivity similar to that of GRP with respect to the releases of insulin and PP. Glucose stimulated a biphasic response of insulin, but no response of PP. The relative secretion of PP from the dorsal vs. the ventral portions of the rat pancreas following stimulation by carbachol and GRP (10(-7) M) was 19% and 22%, respectively, while that of insulin was 289% and 382%, respectively. These data show that peptidergic nerves may play a role in the secretion of PP as with that of insulin.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1511950 TI - Exposure to hepatitis B virus in the general population of Hisayama, Japan: significance of isolated antibody to hepatitis B surface antigen in general population. AB - Cross-sectional survey on the prevalence of hepatitis B serological markers was performed in 2,411 residents who accounted for 74.4% of the population aged 40 and over and living in Hisayama Town, Japan, in 1983. Overall prevalences were 40.7% for both anti-HBs and anti-HBc, 6.1% for isolated anti-HBs and 5.4% for isolated anti-HBc. The condition with isolated anti-HBs was different from those with isolated anti-HBc and both anti-HBc and anti-HBs as follows. The titer of anti-HBs in isolated anti-HBs positive samples was significantly lower than that in both anti-HBs and anti-HBc positive ones (46.2 +/- 5.4 vs. 83.2 +/- 2.8, mean +/- SE, p less than 0.001). The presence of isolated anti-HBs was neither significantly more frequent in males nor related to the risk of liver damages in contrast with that of anti-HBc with or without anti-HBs. These findings suggest that isolated anti-HBs pattern with the absence of anti-HBc in general population was not due to prior HBV infection, but due to natural immunization with HBsAg. PMID- 1511951 TI - Prevalences of hepatitis B surface antigen carriers and liver damages in the general population of Hisayama, Japan. AB - The prevalences of hepatitis B surface antigen (HBsAg) carriers and liver damages were studied in 2,411 residents aged 40 and over and living in Hisayama, Japan in 1983. Hepatitis B virus (HBV) associated markers were all measured by radioimmunoassay. HBsAg carriers were found in 2.3 per cent of the residents. Hepatitis B e antigen and antibody to hepatitis B e antigen were positive in 8.9 per cent and 80.4 per cent, respectively, of HBsAg carriers. The prevalences of liver damages in HBsAg carriers were compared with 1095 who had none of HBV markers (neither anti-HBc nor anti-HBs). The prevalences of abnormal aminotransferase level in sera were not different between HBsAg carriers and those who had none of HBV markers. A history of jaundice and/or hepatitis was evident in 32.3 per cent of male carriers and 24.0 per cent of female ones, being significantly more than those without HBV markers (13.1 per cent and 5.8 per cent, p less than 0.05 and p less than 0.005, respectively). These results indicate that, among HBsAg carriers aged 40 and over, few have active clinical signs of hepatitis, although about 20 per cent of them have histories of symptomatic hepatitis due to hepatitis B. PMID- 1511952 TI - [Human immunoglobulin heavy-chain gene intronic enhancer segment HE2 (microB) functions as a major B-cell specific cis-element at cellular level as well as in transgenic mice]. AB - Immunoglobulin heavy-chain (IgH) gene expression is regulated in a large part of the IgH gene intronic enhancer which is composed of certain protein-binding motifs. These motifs act as a DNA element which is important for the regulation of the IgH gene transcription. Two of these motifs, HE2 and E6 in the human IgH gene intronic enhancer, are considered to affect the B cell-specific gene expression. To examine the true function of the HE2 and E6 motifs in vivo, we established transgenic mouse lines. A 3'deletion mutant of the IgH gene intronic enhancer which includes an active HE2 motif showed almost the same degree of transcriptional activity and tissue-specificity as the whole IgH gene intronic enhancer. Still more, using the luciferase-assay, it was confirmed at cellular level that the HE2 motif plays an important role in the tissue-specific activity of the IgH gene intronic enhancer. On the other hand, the E6 motif was unable to sufficiently produce the B cell-specific expression in vivo and showed enhancer activity in some non-B cells. In transgenic mice, the IgH gene intronic enhancer functioned not only in B-lymphocytes but also in chorid plexus cells which are similar to glial cells. This suggests the existence of common gene expression control mechanisms between the immune system and the nervous system. PMID- 1511953 TI - Removal of intrahepatic cholesterol stones by the combination of percutaneous pneumatic balloon dilatation and cholangioscopic lithotomy. AB - A 53-year-old man presented with a common hepatic duct stone and was also found to have an incarcerated stone, which was thought to consist of cholesterol, in the intrahepatic bile duct of the right lobe. After operative choledocholithotomy, removal of the intrahepatic cholesterol stone was accomplished with percutaneous cholangioscopic lithotomy (PCL) via a choledochal drainage route after pneumatic balloon dilation of a stricture, followed by internal stenting. Although case reports of primary cholesterol hepatolithiasis with some characteristic clinical features have increased recently in Japan, the natural history and clinical course after non-surgical intervention remain uncertain because of the rarity of this disease entity and lack of long-term follow-up studies. We concluded that intrahepatic cholesterol stones can be removed with percutaneous cholangioscopic lithotomy (PCL) without hepatectomy because ductal inflammatory changes and liver parenchymal atrophy, which are indications for surgical intervention, are seldom encountered in primary cholesterol hepatolithiasis. PMID- 1511954 TI - Primary papillary adenocarcinoma in the third portion of the duodenum. AB - We herein report a rare case of papillary adenocarcinoma which occurred in the third portion of the duodenum. The patient was a 62-year-old Japanese male who was admitted due to vomiting and right lower abdominal pain. No abnormal findings were found in the laboratory examinations. After a diagnosis of primary duodenal carcinoma was made by radiologic, endoscopic and ultrasonographic studies, a pancreatoduodenectomy was performed. The histology of the resected specimen revealed papillary adenocarcinoma, with invasion reaching to the pancreatic body. Some characteristic features of the disease are also reviewed. PMID- 1511955 TI - [A study on clonal elimination of auto-reactive thymocytes in bone marrow chimera mice]. AB - Bone marrow (BM) chimera mice were established by injecting BM cells from B10 H-2 congenic or recombinant mice (Mls-1b) into lethally irradiated AKR (Mls-1a) mice in order to elucidate what type of cells were responsible for intrathymic clonal elimination of self-reactive V beta 6+T cells that are reactive to Mls-1a plus I E products. When I-E+ mice were donors, V beta 6+ SP thymocytes were not eliminated. However, in chimeras where B10 (I-Ab, I-E-) or B10.A(4R)(I-Ak, I-E-) mice were donors, variable proportions of V beta 6+ SP cells were observed. These differences appeared to be attributable to the difference in affinity between class II antigens expressed on BM derived cells and Mls-1a on recipient cells. When AKR mice were reconstituted with BM cells from both B10 and AKR mice, V beta 6+ SP thymocytes were eliminated according to frequencies of the AKR derived cells. These findings collectively indicate that the BM derived thymic stromal cells are essential for the clonal elimination of V beta 6+ cells. However, in GVHR chimeras prepared by injecting of both BM cells and splenic T cells from the same donor mice, V beta 6+ cells were not eliminated at all any periods after BMT. Significantly high number of V beta 6+ SP thymocytes seen 1 week after BMT were shown to be the splenic T cellsinjected with BM cells or their descendants. By contrast, the proportions of the V beta 6+ SP cells in GVHR chimeras 5 weeks after BMT fell within the same range as those of normal donor mice. These V beta 6+ cells were derived from BM precursors. These results reveal that acute GVHR in the thymus results in abrogation of clonal elimination of self reactive T cells in the thymus. PMID- 1511956 TI - [Quantitative analysis of DNA synthesis and cell condensation in the oligodactylic rat hand plate]. AB - In order to clarify the teratogenic mechanism of oligodactyly which occurs during the hand plate development, pre-axial oligodactyly was induced in rat by myleran treatment on day 12.0 of gestation. This animal model was consecutively analyzed in the process of the hand plate development. DNA synthesis was quantified by a BrdU/ant-BrdU immuno histochemical study, and cell damage was assessed on the number of reactive macrophages. From these experiments, the following results were obtained. 1) In the oligodactylic rat embryos, the number of DNA synthesizing cells was uniformly reduced in mesenchyme compared to that of the normal embryos on day 13.0. 2) In the pre-axial areas of the diseased hand plate, the number of DNA-synthesizing cells in ectoderm decreased significantly on day 13.5, and the reduction of DNA-synthesis was observed in all areas on day 14.0. 3) The damaged cells in the diseased hand plate were distributed uniformly, regardless of the lack of finger. Thus, it could be speculated that in this myleran induced oligodactylic model both the deficit of mesenchymal cells and the lack of ectoderm derived induction in the fingers were closely implicated in the development of oligodactyly. PMID- 1511957 TI - [Effects of nonthermal stresses on brown adipose tissue thermogenesis]. AB - Repetitive intermittent immobilization stress has been shown to induce an improved cold tolerance through an enhanced capacity of nonshivering thermogenesis (NST). In the present study, effects of immobilization (3 hrs daily for 4-5 weeks), exercise training (running with treadmill 30 min daily, 30 m/min under 8 degrees inclination for 4-5 weeks) and chronic corticosterone treatment (subcutaneous injection at a dose of 0.3 mg/100 g for 4-5 weeks) were investigated on in vitro and/or in vivo thermogenesis of rat interscapular brown adipose tissue (BAT). BAT thermogenesis in vitro was measured in the minced tissue blocks in Krebs-Ringer phosphate buffer using a Clark type oxygen electrode. DNA content per whole BAT pad was greater in the stressed rats, while it was not affected by exercise training and corticosterone. Noradrenaline-and glucagon-stimulated oxygen consumptions were significantly greater in the stressed rats, while significantly smaller in the trained rats as compared with respective controls. Corticosterone treatment failed to affect those values in terms with both per mg tissue and per whole tissue pad, except the less noradrenaline-stimulated oxygen consumption in terms with per mg tissue and DNA. In vivo thermogenesis was assessed by the changes of temperatures in colon (Tcol), BAT (TBAT) and tail skin (Tsk) induced by noradrenaline or glucagon infusion under anesthesia Noradrenaline and glucagon increased the TBAT and the extent of increase was greater in the stressed rats. These results indicated: 1. Repetitive immobilization stress induces the tissue hyperplasia and enhances thermogenic activity of BAT. 2. Exercise training suppresses BAT thermogenesis. 3. Chronic corticosterone administration does not affect BAT thermogenesis. It may be concluded that the enhancing or suppressing effect of nonthermal stress on BAT thermogenesis is due to other factor(s) than corticosterone. PMID- 1511958 TI - [Spinal neurons activated by ventral root afferents in rats: their physiological properties, distribution in the spinal cord and rostral projection]. AB - The present experiment was designed to locate spinal neurons which are activated by afferent fibers in the ventral roots, and once found, to study their receptive field and rostral projection. After dorsal roots L1 approximately S4 on the left side were cut under a binocular microscope, stimulus was applied to ventral roots and extracellular responses were recorded using a glass microelectrode filled with fast green FCF. Sixty-four neurons were activated by stimulating ventral roots at 1.2-27.8 x T of the lowest threshold fibers of the ventral root. Six neurons were classified as wide dynamic neurons and 29 as high threshold neurons according to their response patterns to the periphery. Twelve neurons out of 29 were unresponsive to cutaneous stimulation, and located lamina V, suggesting that they innervate visceral organs. Thirty-five neurons (54.6%) were nociceptive nerons, most of which were located in laminae V and VI. In 6 neurons out of 35 nociceptive neurons (17.1%), rostral projection was confirmed by the collision block method and the ability to respond to high frequency stimuli with constant latency. Our results suggest that some spinal neurons activated primary affernt fibers in ventral roots stimulation are nociceptive and some of them are rostral projecting neurons which are antidromically activated ventral quadrants of the spinal cord. PMID- 1511959 TI - [Expression of granulocyte-macrophage colony-stimulating factor mRNA by inflammatory cells in the sarcoid lung and its clinical significance]. AB - T lymphocytes and alveolar macrophages accumulating in the lower respiratory tract of patients with pulmonary sarcoidosis are known to be activated to produce several cytokines, presumably leading to granuloma formation within the lung. I hypothesized that these cells produce colony-stimulating factors (CSF), which have been shown to affect the proliferation and function of monocyte/macrophage lineage cells. To test this hypothesis, I tried to detect mRNA encoding CSFs in cells obtained by bronchoalveolar lavage using a reverse transcription-polymerase chain reaction. Macrophage-CSF mRNA was detected in all subjects examined and interleukin 3 mRNA in none. Granulocyte-macrophage CSF (GM-CSF) mRNA was detected in 15 of 20 patients with pulmonary sarcoidosis, whereas it was detected in none of the farmer's lung disease patients and normal controls. The sarcoid patients whose BAL cells expressed GM-CSF mRNA had more active disease than those patients whose BAL cells did not, as judged from clinical and laboratory findings. These results indicate that GM-CSF produced by the inflammatory cells plays a substantial role in the formation or maintenance of the sarcoid lesion. PMID- 1511960 TI - Functional and phenotypic analyses of thymic low density adherent cells from murine bone marrow chimeras--influence on thymocyte differentiation. AB - Previous studies from this laboratory demonstrated a malfunction of the thymus of C3H mice to induce normal level of thymocyte differentiation. Thymocytes developed in the C3H thymus showed depressed proliferative responses to stimulation with anti-CD3 antibody compared with those developed in the other strains. This study was conducted to analyze immunological functions of the thymic stromal cell population in the C3H mice. Using allogeneic bone marrow (BM) chimeras established by reciprocal combination of AKR and C3H mice as donor or recipient, antigen presenting cell (APC) function of low density adherent cells (LDAC) in the thymus was analyzed. The thymic LDAC from C3H mice or [AKR----C3H] BM chimeras where AKR were BM donors and C3H were recipients contained high proportion of Mac-1+ cells as compared to AKR mice or [C3H----AKR] chimeras. The proportion of Mac-1+ cells paralleled the IL-1 secreting ability of the LDAC. Thus, the higher proportion of Mac-1+ cell in the thymus may be responsible for low accessory function observed in C3H thymuses. However, when APC function was analyzed using various T cell hybridomas or a T cell line, the APC functions did not necessarily correlate to the proportions of Mac-1+ cells and amounts of IL-1 produced by the LDAC. When proliferative responses of thymocytes to anti-CD3 stimulation were analyzed in the presence of prostaglandins, PGE-2 inhibited more profoundly the responses of [AKR----C3H] and normal C3H mice than those of [C3H-- -AKR] and normal AKR mice. Furthermore, a prostaglandin inhibitor, indomethacin, reversed the depressed responses of the former thymocytes which had developed in the C3H thymus. These findings suggest that the hyporesponsiveness of thymocytes from [AKR----C3H] chimeras to anti-CD3 stimulation may be attributable to their increased sensitivity to prostaglandin produced by LDAC. PMID- 1511961 TI - [A structure of ordering and display system by adopting computer for receipt in a medical clinic]. AB - Online and display system for the result of laboratory examination were constructed by adopting a computer for receipt. The computer for receipt was expanded to a new schedule file and a management schedule file. Consequently, reservation system of medical clinic was made and check seats of order decreased in number. It was considered that patients can understand conditions of their illness and results of laboratory examination very easily with this system. PMID- 1511962 TI - Data watch. Hospitals strive to improve customer service. PMID- 1511963 TI - Managed care. PMID- 1511964 TI - Annual survey: executive compensation under fire. AB - Compensation of health care executives has continued to grow, largely pushed along by such factors as continuing turnover in top management positions in hospitals, according to the 1992 Hay hospital management/professional survey of compensation and benefits data from over 1,200 U.S. hospitals. And although pay increases are moving up faster among top hospital executives than in industry, overall hospital executive pay still lags. In addition, survey results look at such issues as linking executive pay to various measures of performance. PMID- 1511965 TI - Survey: many CEOs overlook PR staff's role in strategic planning. AB - Many CEOs say public relations is vital to their hospital's success, but don't give their PR officers a strategic role, a recent survey shows. CEOs with narrow views are "losing a great opportunity," says Richard Norling, president and CEO of Fairview Hospital and Healthcare Services, Minneapolis. PMID- 1511966 TI - Seven historical lessons about community relations. PMID- 1511967 TI - New national survey finds MDs, administrators, public at odds. PMID- 1511968 TI - HCFA's bundled CABG payment project yields results, insights. PMID- 1511969 TI - Laboratory regulations create new opportunities for hospitals. PMID- 1511970 TI - CFOs identify ways hospitals can build financial strength. PMID- 1511971 TI - Hospital-based home care poised for growth in 1990s. PMID- 1511972 TI - Taking a serious look at patient expectations. PMID- 1511973 TI - Molecular screening and fetal diagnosis of beta-thalassemia in the Italian population. AB - This paper reports our experience of molecular screening and fetal diagnosis of beta-thalassemia in 457 at risk couples of Italian descent. Molecular screening was carried out by dot blot analysis on amplified DNA with oligonucleotide probes complementary to the eight most common mutations in Italians [beta zero 39 (C--- T); beta zero 6 (-A); beta+ -87 (C----G); beta+ IVSI nt 110 (G----A); beta zero IVSI nt 1 (G----A); beta+ IVSI nt 6 (T----C); beta zero IVSII nt 1 (G----A); beta+ IVSII nt 745 (C----G)]. By using this approach, we have been able to define the mutation in 92.8% of cases. The rest (all but four) were defined by direct sequencing and this led to the detection of nine rare mutations [beta zero 76 ( C); beta+ IVSI nt 5 (G----A); beta+ IVSI nt 5 (G----C); beta+ IVSI -1 (cod 30) (G ---C); beta+ -87 (C----T), beta zero -290 bp del.; beta+ -101 (C----T)], and to the characterization of a novel mutation consisting of the deletion of the G at the invariant AG of the IVSII splice acceptor site of the beta-globin gene (beta IVSII nt 850 -1 bp). In the remaining four cases, the beta-globin gene showed entirely normal sequences and the beta-globin gene cluster was intact, as indicated by Southern blot analysis. Fetal diagnosis was carried out by dot blot analysis with the oligonucleotide probes defined in the parents. The procedure is simple and reliable, and the results can be obtained within 1 week of sampling. No misdiagnosis has so far occurred. The results indicate that fetal diagnosis of beta-thalassemia by DNA analysis may be obtained in practically all cases (even in a population showing marked heterogeneity of beta-thalassemia) by the combination of dot blot analysis for detecting common mutations, and direct sequencing for defining those that are uncommon. PMID- 1511974 TI - The majority of the marker chromosomes in Japanese patients with stigmata of Turner syndrome are derived from Y chromosomes. AB - DNA analyses of 41 individuals with stigmata of Turner syndrome and a 45,X/46,X+mar or 46,X+mar karyotype were carried out. Southern-blot analysis employing 17 Y-specific probes were used to determine whether the marker chromosome was Y-chromosomal in origin. Of the 41 DNA samples from these patients, 23 contained detectable Y-chromosomal DNA. Points of chromosome breakage were distributed over the entire length of the Y long arm. Three individuals, who carry different portions of the Y chromosome, had developed gonadoblastoma. GBY (the gonadoblastoma locus on the Y chromosome) is mapped proximal to DYS132, midway between the 13 Yq loci that we have studied. We also used a polymerase chain reaction technique that could detect 7 loci over the length of the Y chromosome. This technique may be useful for the rapid assessment of marker chromosomes, especially for evaluating the risk of gonadoblastoma. PMID- 1511975 TI - No evidence for linkage of familial hypertrophic cardiomyopathy and chromosome 14q1 locus D14S26 in a Chinese family: evidence for genetic heterogeneity. AB - To understand the molecular basis of familial hypertrophic cardiomyopathy (FHC) in the Chinese population, a family with FHC was investigated. Nineteen family members who were 16 years of age or older were examined by M-mode or two dimensional echocardiography. Eight members were diagnosed to be affected echocardiographically or clinically. Lymphocytes isolated from 20 family members were successfully transformed into permanent lymphoblastoid cell lines by Epstein Barr virus. Three genomic DNA probes (CRI-L436, CRI-L329, and pSC14) that were derived from chromosome 14q1 loci and demonstrated to be linked closely to FHC were used to probe this family. Using the techniques of restriction fragment length polymorphism (RFLP) and linkage analysis, the probe CRI-L436, which recognized locus D14S26, was found informative in this family. The lod scores were -2.0 at theta = 0.025 and -1.49 at theta = 0.05. Thus, there was no evidence of linkage between the locus D14S26 and the gene for FHC in the pedigree studied. In addition, polymerase chain reaction (PCR) amplification did not indicate a mutation on exon 13 of the beta cardiac myosin heavy chain gene as previously reported. Our data suggest that FHC is a genetically heterogeneous disease. PMID- 1511976 TI - Molecular cytogenetic analysis of a familial 8p23.1 deletion associated with minimal dysmorphic features, seizures, and mild mental retardation. AB - We report a family in which three members presented with minimal phenotypic abnormalities, normal intelligence to mild mental retardation, and a cytogenetically terminal chromosome deletion at band 8p23.1 Whole chromosomal painting with a chromosome 8-specific DNA library confirmed this familial chromosome abnormality as a deletion, while fluorescence in situ hybridization with telomeric probes demonstrated the presence of telomeres at the deletion site. Coagulation studies were additionally performed to evaluate the purported location of the coagulation factor VII regulator gene at 8p23.1. A review of the clinical findings of seven cases of del(8)(p23.1) is presented. PMID- 1511978 TI - Fragile site (16) (q22). III. Segregation analysis. AB - The rare autosomal fragile site, fra (16) (q22), is the most common of all rare autosomal fragile sites and has a heterozygote frequency of about 5%. Evidence for it was found following the segregation expected from a simple codominant trait with complete penetrance; this is in contrast to a variety of other rare autosomal fragile sites. Based on the analysis of 12 families in which fra (16) (q22) is segregating, we found that, whereas complete penetrance could be confirmed, the transmitting parent was significantly more likely to be of the female sex. On the other hand, there was no evidence for preferential transmission to offspring of either sex. PMID- 1511977 TI - Identification of crossovers in Wilson disease families as reference points for a genetic localization of the gene. AB - Wilson disease (WD) is an autosomal recessive disorder of copper metabolism. A minimum recombinant analysis using D13S22, ESD, RB1, D13S31, D13S55, D13S26, D13S39, and D13S12, all localized at 13q14-q22, has been carried out in 20 WD families of Northwest-European origin. No inconsistencies have been observed with respect to locus order or location of the WD locus (WND) compared with previous linkage studies. D13S31 was mapped as the closest marker proximal to WND, whereas D13S55 and D13S26 were mapped as the closest markers distal to WND. We have identified a crossover between WND and D13S31 in one family and a crossover between WND and D13S55 in another. These crossover sites can be used as reference points for new chromosome 13q14-q21 markers, and are therefore important for a more accurate mapping of the WD locus. PMID- 1511979 TI - Physical fine mapping of genes underlying X-linked deafness and non fra (X)-X linked mental retardation at Xq21. AB - Linkage studies and cytogenetically visible deletions associated with nonspecific X-linked mental retardation (XLMR) and a specific form of deafness (DFN3) have indicated that the genes responsible for these disorders are located at Xq21. Using DNA probes from this region, we have studied several overlapping deletions spanning different parts of Xq21. This has enabled us to assign the DFN3 gene and a gene for nonspecific XLMR to an interval that encompasses the locus DXS232 and that is flanked by DXS26 and DXS121. PMID- 1511980 TI - Beta-globin gene cluster haplotypes in Yanomama Indians from the Amazon region of Brazil. AB - Six polymorphic restriction enzyme sites in the beta-globin gene cluster were investigated in Yanomama Indians from the Amazon region of Brazil, using the polymerase chain reaction (PCR) technique. Four haplotypes were identified; the haplotype frequency distribution is similar to those reported for Polynesians, Micronesians and most Asian populations. PMID- 1511981 TI - Ornithine transcarbamylase (OTC) deficiency in a female patient with a de nova deletion of the paternal X chromosome. AB - A girl with ornithine transcarbamylase (OTC) deficiency was investigated for molecular and cytogenetic abnormalities that might explain this phenotype. Analysis with polymorphic DNA markers indicated that the patient did not inherit paternal alleles of the OTC locus, but that she did inherit the proximal locus DXS7 and the long arm of chromosome X. High-resolution cytogenetic analysis of the patient indicated a deletion of Xp11.4-p21, whereas both parents had normal karyotypes. Since the mother might be heterozygous according to biochemical tests, a second mutation within the maternal OTC gene cannot be excluded. PMID- 1511982 TI - A dominant mutation in the COL1A1 gene that substitutes glycine for valine causes recurrent lethal osteogenesis imperfecta. AB - Type I collagen chains of a proband from a family with recurrent lethal osteogenesis imperfecta (OI) migrated as a doublet when submitted to gel electrophoresis. Cyanogen bromide (CNBr) peptide mapping demonstrated that the post-translational over-modifications were initiated in alpha 1ICB7. Chemical cleavage of cDNA-RNA heteroduplexes identified a mismatch in the alpha 1I cDNA; this mismatch was subsequently confirmed by sequencing a 249-bp fragment amplified by the polymerase chain reaction. A G to T transition in the second base of the first codon of exon 41 resulted in the substitution of glycine 802 by valine. This mutation impaired collagen secretion by dermal fibroblasts. The over modified chains were retained intracellularly and melted at a lower temperature than normal chains. Collagen molecules synthesized by parental fibroblasts had a normal electrophoretic mobility, but hybridization of genomic DNA with allele specific oligonucleotides revealed the presence of the mutant allele in the mother's leukocytes. The mutation was not detected in her fibroblasts consistent with the protein data. These results support the hypothesis that somatic and germ line mosaicism in the phenotypically normal mother explain the recurrence of OI. PMID- 1511983 TI - Molecular studies of parental origin and mosaicism in 45,X conceptuses. AB - The present report summarizes molecular studies of parental origin and sex chromosome mosaicism in forty-one 45,X conceptuses, consisting of 29 spontaneous abortions and 12 liveborn individuals with Turner syndrome. Our studies indicate that most 45,X conceptuses have a single, maternally derived X chromosome, regardless of whether the conceptus is liveborn or spontaneously aborted. In studies of mosaicism, our identification of X- and Y-chromosome mosaics among 45,X spontaneous abortions indicates that mosaicism does not ensure survival to term of 45,X fetuses. However, the incidence of sex chromosome mosaicism is substantially higher in liveborn than in aborted 45,X conceptuses, indicating that the presence of a second cell line increases the likelihood of survival to term. PMID- 1511984 TI - Crossed renal ectopia with pelvic lipomatosis: a new syndrome involving chromosome 1. AB - An 18-year-old male patient is described who possesses both kidneys on one side (crossed renal ectopia), together with pelvic lipomatosis. In general, lipomatosis is benign, but here the tissue shows the rare feature of malignancy. Chromosomally, the patient is typically characterised by somatic translocations involving chromosome 1 (37% metaphases); these almost always exhibit a whole chromosome translocation with chromosome 6 (35%), although involvement of chromosome 1 with chromosome 8 is present in 2% of metaphases. Other chromosomal features encountered in Giemsa-stained and G-banded preparations from lymphocyte cultures include the prevalence of a small Y chromosome in 25% of metaphases, the presence of marker dots in 20%, and acrocentric associations in 8%-10% of metaphases. However, more than 50% of metaphases have a normal 46XY karyotype with a normal-sized Y-chromosome. Crossed renal ectopia with pelvic lipomatosis can therefore be assigned to a new syndrome characterised by a whole-chromosome translocation involving chromosomes 1 and 6. PMID- 1511985 TI - Geographic distribution and genealogy of mutation 207 of the lipoprotein lipase gene in the French Canadian population of Quebec. AB - Mutations in the lipoprotein lipase (LPL) gene, leading to partial or total inactivation of the enzyme, result in a hereditary clinical syndrome called familial LPL deficiency. The French Canadian population, which is primarily and historically located in the province of Quebec, has the highest worldwide frequency of LPL-deficient patients. We have analyzed the prevalence, spatial distribution, and genealogy in the Quebec population of a LPL gene mutation, M 207 (P207L in conventional notation), which changes the amino acid proline to leucine in position 207 of the LPL protein and inactivates the enzyme. Our results show that M-207 is the most prevalent LPL gene mutation among French Canadians and accounts for the largest proportion of LPL-deficient patients in this population. Genealogical reconstruction of French Canadian LPL-deficient patients point to 16 founders of M-207, all of whom migrated to Quebec in the early seventeenth century from the north-western part of France, especially from the region of Perche. Most of the carriers of M-207 are, at present, found in Charlevoix, Saguenay-Lac-St-Jean regions of eastern Quebec. On the basis of the number of homozygote M-207 LPL-deficient patients so far identified, we estimate that there are at least 31,000 carriers of this mutation in the province of Quebec. This constitutes a large pool of individuals at risk for atherosclerosis and other lipid-related diseases, since LPL deficiency is considered to be a significant contributing factor in the etiology and development of these diseases. PMID- 1511986 TI - Two new human hemoglobin variants caused by unusual mutational events: Hb Zaire contains a five residue repetition within the alpha-chain and Hb Duino has two residues substituted in the beta-chain. AB - With rare exceptions, the more than 600 human hemoglobin variants described are caused by a single point mutation. Other abnormal features, such as unequal crossing-over, frameshift mutagenesis or double mutations in the same polypeptide chain, have seldom been encountered. We report two new variants caused by such rare mutational events. Hb Zaire [alpha 116(GH4)-His-Leu-Pro-Ala-Glu-117 (GH5)] is the second example in which a short amino acid sequence is inserted within the alpha-chain. This abnormal hemoglobin results from a tandem repetition of 5 amino acid residues, from sequence 112 through 116, at the end of the GH corner. Hb Duino is an unstable hemoglobin. It presents within the same beta-chain, the association of two rare point mutations; these substitutions are those found in Hb Newcastle [beta 92(F8)His----Pro] and in Hb Camperdown [beta 104(G6)Arg--- Ser]. Family studies demonstrated that the Hb Newcastle abnormality was a de novo mutation of a gene already carrying the Hb Camperdown substitution. PMID- 1511988 TI - A novel homozygous missense mutation in the protein C (PROC) gene causing recurrent venous thrombosis. AB - A novel homozygous CCC----CTC (Pro 247----Leu) substitution was detected in the protein C genes of a patient, born to consanguineous parents, with inherited type 1 protein C deficiency and recurrent venous thrombosis. Since one of four heterozygous relatives was also clinically affected, the condition appears to be inherited as an incompletely recessive trait in this family. PMID- 1511987 TI - Assignment of the gene for human spasmolytic protein (hSP/SML1) to chromosome 21. AB - A human cDNA corresponding to the porcine pancreatic spasmolytic protein (PSP) was isolated, and the recombinant clone was originally termed hSP for human spasmolytic protein. Later, the term SML1 for spasmolysin was suggested for the human gene. This protein shows a remarkable sequence homology to pS2, a protein coded by an estrogen-induced gene isolated from the breast carcinoma cell line MCF-7. Although, at the DNA level, the gene sequences pS2 and hSP/SML1 display insufficient homology for cross-hybridization, their expression in tumor cells occurs with remarkable coordination. The human pS2 gene sequence has been assigned to chromosome 21, and we have therefore attempted to map the hSP/SML1 gene by using cDNA and Southern blotting of genomic DNAs from a panel of human rodent somatic cell hybrids carrying different complements of human chromosomes. Interestingly, the hSP/SML1 gene is also localized on chromosome 21. PMID- 1511989 TI - Two different missense mutations at Arg 178 of the protein C (PROC) gene causing recurrent venous thrombosis. AB - Non-identical missense mutations were identified at Arg 178 in the protein C genes of two patients with heterozygous type 1 protein C deficiency and recurrent venous thrombosis. PMID- 1511990 TI - No abnormalities in the NAD+ ADP-ribosyltransferase (polymerizing) gene of transformed cells from a Fanconi's anemia patient. PMID- 1511991 TI - A polymorphic complex dinucleotide repeat at the telomeric D8S7 locus. AB - Two cosmids isolated from a flow-sorted chromosome 8 library by hybridization with pSW50 (D8S7) were screened for GT microsatellite sequences. Both contained a positive 900-bp Hind III-Xba I fragment. Sequencing revealed a complex dinucleotide repeat. Flanking oligonucleotide primers were synthesized, and the polymerase chain reaction products produced by these primers were typed within the CEPH panel of families. A two-allele polymorphism was identified that is in linkage disequilibrium with a previously described insertion-deletion polymorphism at this locus. PMID- 1511992 TI - BF and C3 genetic polymorphisms in Kaingang Indians from southern Brazil. AB - The distribution of C3 and BF variants was determined in a sample of 239 Kaingang Indians. The corresponding gene frequencies were as follows: BF*S = 0.9393, BF*F = 0.0356, BF*S05 = 0.0251, C3*S = 0.9769, C3*F = 0.0231. The presence of the BF*S05 allele, which has previously been found only in a Brazilian population, suggests that this allele originated in Amerindians. The comparatively low degree of polymorphism with high frequencies of BF*S and C3*S is in accordance with the relatedness of the Kaingang with other Amerindians, Eskimos and Asian populations. PMID- 1511993 TI - Limited genetic diversity in polynesians reflected in the highly polymorphic 3'HVR alpha-globin gene marker. AB - Polynesians from five distinct island groups were studied with DNA probe alpha 3'HVR, a highly polymorphic VNTR (variable number of tandem repeats) minisatellite region associated with the alpha-globin gene cluster. Results showed a paucity of genetic heterozygosity together with clustering of alpha 3'HVR alleles with alpha-globin DNA haplotypes and alpha-globin gene rearrangements. This restricted diversity is consistent with population bottlenecks in the colonization of Polynesia. PMID- 1511994 TI - Complement genetic markers in schizophrenia: C3, BF and C6 polymorphisms. AB - Polymorphic variants of C3, BF and C6 complement factors have been investigated in schizophrenic patients subdivided according to the existence or not of a family history of both schizophrenia and other psychiatric disorders. To analyze the contingency tables, besides the usual methods, log-linear models have been fitted. Significant associations have been found in the C3 system, with a decrease of C3*F in patients (contradicting previous findings), and in the BF system, with a decrease of FS phenotype among patients (confirming some previous results). No association has been found for the C6 polymorphism (in accordance to previous results). Therefore, the present findings only partially confirm previous results and do not clarify the relationship between complement genetic markers and schizophrenia, stressing some statistical difficulties. PMID- 1511995 TI - Serum protein groups (Hp, GC, C3) in patients with gastric carcinoma. AB - The phenotypes and gene frequencies of 3 serum protein systems (Hp, GC and C3) were studied in 114 consecutive patients from all over Greece with gastric carcinoma. Healthy Greeks studied previously in our Department served as controls. No significant differences were found between patients and controls concerning Hp. Significant differences were found in the GC and C3 systems; GC 2 1 and C3F phenotype as well as C3*F gene frequencies were significantly higher in patients than in controls. PMID- 1511996 TI - Complementation in Zellweger syndrome: biochemical analysis of newly generated peroxisomes. AB - The Zellweger syndrome is characterized by a defect which results in the abnormal biogenesis of peroxisomes. As a consequence, metabolic activities associated with peroxisomes such as the oxidation of very long chain fatty acids, the synthesis of plasmalogens, and the catabolism of phytanic and pipecolic acids are impaired. Since this disorder is genetically heterogeneous and several complementation groups are known, we were able to study the normalization of peroxisomal activity during the process of complementation. The restoration of catalase and dihydroxyacetone phosphate acyltransferase activities peaked within 3-4 days postfusion while the oxidation of lignoceric acid was much delayed (7-8 days). Electron microscopy indicated that by 6 days following hybridization, peroxisome structure and density in heterokaryons was comparable to normal control cells. The heterogenous biochemical response during peroxisome normalization could be due to several factors including a possible requirement for restoration of peroxisomal structural integrity for maximum activation of certain metabolic pathways. PMID- 1511998 TI - The first case of familial amyloidotic polyneuropathy (FAP Met30) in the Finnish population. AB - Finnish hereditary amyloidosis-Meretoja (FAP type 4) is the predominating type of hereditary amyloidosis in the Finnish population, found in more than 200 individuals. We present a Finnish family with familial amyloidotic polyneuropathy (FAP Met30), a type of amyloidosis hitherto not described in the Finnish population. Genealogical tracing back to the 18th century revealed no connections with Swedish FAP families, but introduction from Sweden is the most probable origin of the FAP Met30 gene. PMID- 1511997 TI - Hereditary nonspherocytic hemolytic anemia due to pyruvate kinase deficiency: a prevalence study in Quebec (Canada). AB - Fifty-eight cases of hereditary nonspherocytic hemolytic anemia due to pyruvate kinase deficiency were collected from both laboratories that have performed the assay since 1972 and from attending physicians in the province of Quebec. Using the postal addresses of the probands, a prevalence map was constructed according to the administrative regions of the province of Quebec. The prevalence was found to be higher in eastern Quebec (1/81,838) than in western Quebec (1/139,086). Fifty probands were of French Canadian origin whereas the remaining 6 were recent immigrants. PMID- 1511999 TI - A rapid method for diagnosis of the Lebanese allele in the low-density lipoprotein receptor gene. AB - The Lebanese allele in the low-density lipoprotein receptor gene is one of the alleles which results in the disease familial hypercholesterolemia. We describe a rapid method for detection of the Lebanese allele, using the polymerase chain reaction to amplify part of exon 13, intron 14 and all of exon 14. The amplified DNA is then digested with HinfI which distinguishes between the normal and Lebanese alleles. A previously unidentified HinfI site is described in the intron. HinfI fragments are separated using polyacrylamide gel electrophoresis, and visualized by ethidium bromide staining. PMID- 1512000 TI - Uniparental origin of sex chromosome polysomies. AB - The parental origin of the additional sex chromosomes in 8 cases with high-order sex chromosome polysomies was determined using DNA polymorphisms. The additional sex chromosomes were paternally derived in 3 48,XXYY cases, and maternal in origin in 1 48,XXXY case and 4 49,XXXXY cases. Thus, all extra chromosomes, within a particular patient, were always derived from only one parent. Their most likely origin was successive nondisjunction at the first and second meiotic division in one germ cell. The mechanism involved remains unclear, but appears to be independent of parental ages. PMID- 1512001 TI - GC and C3 serum groups in peptic ulcer. AB - The phenotypes and gene frequencies of two serum protein systems (GC, C3) were studied in 238 consecutive patients with peptic ulcer from all over Greece. 173 patients had duodenal ulcer and 65 had gastric ulcer. Healthy Greeks studied previously in our department served as controls. No significant differences were found between the studied groups and the controls as far as GC was concerned. However, significant differences emerged in C3; the C3*F gene was almost twice more common and the C3F phenotype almost three times more frequent in patients than in controls. PMID- 1512002 TI - Interaction between ABO and haptoglobin systems in a Bengalee population. AB - Blood samples from 2,232 individuals of a Bengalee Caste Hindu population were investigated in an attempt to confirm the association between the ABO and haptoglobin (HP) systems previously found in populations of European origin. Indians differ from Europeans in having lower HP*1 and higher ABO*B frequencies. In spite of this, as in previous studies, a weak HP/ABO association was found with a significantly lower HP*1 allele frequency in blood group O versus other ABO groups. PMID- 1512003 TI - Haplotype analysis and polymorphic frequency data at two factor IX loci (F9-192 and F9-Hha1) in a Chinese population. AB - Gene frequencies and haplotypes for two factor IX markers, F9-192 and F9-Hha1, were determined in a Chinese population. The frequencies for F9-192 are 0.86 for A and 0.14 for G. For F9-Hha1, the gene frequencies are 0.69 for - and 0.31 for +. Haplotype analysis revealed that the two polymorphic sites are in linkage equilibrium and, thus, are useful markers for genetic counseling of Asian families in which hemophilia B exists. PMID- 1512004 TI - PI*E Tripoli: a new allele in the alpha-1-antitrypsin system. AB - Genetic variants of the human serum alpha 1-antitrypsin (PI system) were analyzed in a population sample of 110 unrelated Libyans. Four common PI M variants and 3 rare ones, including a new anodal variant designated PI E Tripoli (PI ET) were identified. The estimated allele frequencies were: PI*M1 = 0.623; PI*M2 = 0.205; PI*M3 = 0.132; PI*M4 = 0.018; PI*ET = 0.005; PI*S = 0.005, and PI*T = 0.014. PMID- 1512005 TI - Genetic markers in alcoholic liver cirrhosis. AB - 11 genetic markers were typed in 157 individuals suffering from alcoholic cirrhosis, and compared with a random sample of healthy individuals. No significant differences were found for transferrin, specific group component, orosomucoid, esterase D, phosphogluconate dehydrogenase and adenylate kinase. Strong associations between alcoholic cirrhosis and alpha-1-antitrypsin PI*Z allele, haptoglobin HP*1 allele and acid phosphatase ACP AC phenotype were observed. The biological significance of these associations and their relationships with the development of alcoholic cirrhosis are also discussed. PMID- 1512006 TI - The structure of the Polar Eskimo genealogy. AB - The structure of the genealogy of the Polar Eskimos from the Thule District of North Greenland is studied by a variety of computational and graphical means, some of them novel. It is shown that although the level of inbreeding in the population is low, the genealogy is intricately connected, as if conforming to the requirement that spouses are as unrelated as is possible in a small population. PMID- 1512007 TI - Distribution of F13A phenotypes in Spain: a particularly high frequency of the F13A*2 allele. AB - The distribution of the phenotypes for coagulation factor XIIIA subunit (F13A) of autochthonous individuals from the following five Spanish populations was studied: Galicia, Castilla-Leon, Castilla-La Mancha, Extremadura and Western Andalusia. The frequency values obtained for F13A*2 ranged from 0.248 to 0.311. To date, these values are the highest recorded in the world. PMID- 1512008 TI - In vitro characterization of repair synthesis initiated by T4 endonuclease V on a synthetic DNA substrate. AB - The size of the repair patch produced by E. coli DNA polymerase (Pol I) following the removal of a pyrimidine dimer from DNA in response to the nicking activity of T4 endonuclease (T4 endo V) was determined. A 48-bp DNA containing a pyrimidine dimer at a defined location was labelled in the damaged strand and incubated with T4 endo V and E. coli endonuclease IV. Subsequently, DNA synthesis by DNA Pol I was carried out in the presence of four dNTPs, ATP and DNA ligase. Analysis of the reaction products on a sequencing gel revealed a ladder of only 4 oligonucleotides, 1-4 nucleotides greater in length than the fragment generated by the combined nicking activities of T4 endo V and E. coli endonuclease IV. Thus we conclude that the in vitro repair patch size of T4 endo V is 4 nucleotides and that in some cases the repaired DNA is not ligated. PMID- 1512009 TI - Stereochemical aspects of interaction of DNA binding domain of human progesterone receptor with d(AGGTCATGCT)2. AB - Structures of (i) 66 amino-acid fragment (residues 567-633) from DNA binding domain of human progesterone receptor (hPR), (ii) a ten base pair DNA sequence d(AGGTCATGCT)2 from hormone responsive element (HRE) and (iii) a complex of these two are optimised by computer modelling and molecular mechanics technique using extensive steric constraints from secondary structure predictions, comparison with the structures of known metalloproteins, geometric constraints imposed by tetrahedral coordination with the zinc ion and comparison with structures of DNA binding domains of human glucocorticoid and estrogen receptors (hGR and hER). Structure of the complex was obtained using genetic modification data on steroid receptors and general consensus about protein-DNA interaction. DNA is in distorted B conformation. Sequence dependent as well as protein-induced conformation changes are noticed. There is change in propeller twist, buckle and angle between glycosyl bonds. However, H-bonding network is preserved. The complex is stabilized with eighteen hydrogen-bonds, mainly between peptide side chains and backbone phosphate. There are five specific H-bonds between basic amino acid side chains, Lys 22, Lys 26 and Arg 27, and DNA bases, A1, G3, G16 and A17. Gly 19, Ser 20 and Val 23 are in close proximity of DNA. PMID- 1512010 TI - Characterization of concanavalin A-binding neuronal and glial surface glycoproteins from human foetal brain. AB - Neuronal and glial surface glycoproteins have been isolated from human foetal brains by affinity chromatography on 8 M urea or 6 M guanidine-treated Con A Sepharose 4B at 4 degrees C and three groups of glycoproteins of molecular mass 65-73 kDa, 52-63 kDa and 43-48 kDa have been identified on SDS/PAGE. These glycoproteins exhibited anomalous behaviour on SDS/PAGE, indicating the existence of a gradation of mutually interconvertible protein-SDS aggregates in dynamic equilibrium with one another. Deglycosylation and deacylation did not alter the SDS/PAGE multiple band pattern. Purified glycoproteins contained 160 +/- 90 micrograms carbohydrate/mg protein, and a sialic acid content of 25 +/- 5 nmole/mg protein. The N-terminals were blocked. The glycoproteins moved preferentially on acid/urea/PAGE. Sepharose 6B gel filtration in the absence of lipid and detergents resolved the glycoproteins into an excluded peak I and a low molecular mass peak II. Peaks I and II were non-interconvertible on Sepharose 6B gel filtration or on reversed phase HPLC in an isopropanol/water/TFA gradient system. Both peaks rendered a single fast moving band of identical mobility on acid/urea/PAGE, suggesting that peak I was possibly a micellar aggregate of the monomeric peak II. The glycoproteins were refractory to digestion by trypsin or pronase and reacted identically towards various lectins.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1512011 TI - Lectin binding to complex carbohydrate at the interface: a study by resonance energy transfer. AB - The binding affinity of the oligosaccharide moiety of a neutral glycosphingolipid, asialoGM1, towards Ricinus communis agglutinin (RCAI) was determined for the first time by fluorescence resonance energy transfer (RET). The asialoGM1 was incorporated into a phospholipid (DMPC) vesicle doped with dansylated DPPE and then titrated with an increasing amount of the galactose specific RCAI. The efficiency of RET was determined by a saturable increase in the quenching of 'donor' fluorescence, i.e. the 'trp' residue of RCAI, due to the energy transfer from the 'acceptor' dansyl group on the surface of the vesicle. The apparent binding constant was found to be in the range of 10(5)-10(6) M-1 at 27 degrees C. PMID- 1512012 TI - Rapid isolation of human plasma anti-alpha-galactoside antibody using sugar specific binding to guar galactomannan or agarose. AB - A method of purifying the naturally occurring antibody to alpha-galactoside moiety (anti-alpha-Gal) in human plasma by a single-step affinity chromatography on cross-linked guar galactomannan (CLGG) or agarose (Sepharose 4B) is described. IgG nature of the two preparations, as revealed by agar gel diffusion, as well as their preference for alpha-anomer of galactose, as revealed in inhibition of their agglutination of trypsinized rabbit erythrocytes by sugars, identified them with anti-alpha-Gal. The antibody binding capacity of Sepharose 4B was only a third of that of CLGG. Both gels showed similar dependence on ionic strength for binding. The pH optimum for binding of anti-alpha-Gal to CLGG was 8.0. Significantly anti-alpha-Gal binding to Sepharose was unaffected by CNBr activation and ligand coupling to the gel, thus warning that contaminating plasma could introduce artifacts in agarose-based chromatography of human tissue biomolecules. PMID- 1512013 TI - Modulation of T cell functions by sperm-specific lactate dehydrogenase: fluorescence analysis of immune competent cells and local graft versus host reaction. AB - Immune responses to a well-defined sperm-specific isogenic lactate dehydrogenase C4 (LDH-C4) have been studied in C57Bl/Ks (H-2d) mice after immunization through intra-rectal route. Presence of anti-LDH-C4-antibodies in the sera of females immunized in presence or absence of adjuvant suggested that the immune system of mice becomes exposed to sperm antigens following intrarectal insemination. LDH-C4 primed lymphocytes from both males and females, when transferred in F1 hybrids, suppressed stimulation index of local graft versus host reaction. However, contrary to females, male counterparts which did not elicit measurable anti-LDH C4-antibody titer, showed the presence of a higher proportion of Ly2+ and Ia+ fluorescence labelled cells in the spleen of LDH-C4 administered mice. Results suggest that males are more susceptible for immune suppression of T cell functions through generation of T suppressor cells. Sex differences in relation to immune deviation by intra-rectal administration of sperm-specific LDH-C4 in mice and their consequences in AIDS and AIDS-related complex diseases are described. PMID- 1512014 TI - Conjugated dienes in lipids of apolipoprotein B containing lipoproteins of normal and type 2 (non-insulin-dependent) diabetic patients. AB - Conjugated dienes present in the fatty acyl chains of cholesterol esters and triglycerides associated with plasma apolipoprotein B containing lipoproteins of normal and Type 2 (non-insulin-dependent) diabetic patients (n = 17) have been analysed using second derivative electronic absorption spectroscopy. Characteristic spectral patterns for both normal subjects and Type 2 diabetic patients were observed. Cis, trans and trans, trans conjugated dienes in cholesterol esters of lipoprotein B of Type 2 patients and normal subjects were found to be 41.74 +/- 0.51 mg/litre, 8.20 +/- 0.20 mg/litre (p less than 0.01) and 24.70 +/- 0.33 mg/litre, 9.22 +/- 0.06 mg/litre (p less than 0.01), respectively. Levels of these dienes in triglyceride fraction were 21.21 +/- 0.52 mg/litre, 7.72 +/- 0.02 mg/litre (p greater than 0.05) and 15.49 +/- 0.36 mg/litre, 7.91 +/- 0.11 mg/litre (p greater than 0.05), respectively. PMID- 1512015 TI - Impact of chromium on lipoperoxidative processes and subsequent operation of the glutathione cycle in rat renal system. AB - Oral administration of K2Cr2O7 to male albino rats at an acute dose of 1500 mg/kg body wt/day for 3 days brought about sharp decrease in the activities of glucose 6-phosphate dehydrogenase and glutathione reductase of kidney epithelial cells. The scavenging system of kidney epithelium is also affected as evident by the highly significant fall in the activities of glutathione peroxidase, superoxide dismutase and catalase which ultimately leads to the increase in lipid peroxidation value in kidney cortical homogenate. However, glutathione-s transferase activity in cytosol and glutathione and total thiol content in cortical homogenate were not altered. Chronic oral administration of K2Cr2O7 (300 mg/kg body wt/day) for 30 days to rats lead to elevation in the activities of glutathione peroxidase, glutathione reductase, glutathione-s-transferase, superoxide dismutase and catalase with no change in glucose-6-phosphate dehydrogenase activity in epithelial cells. This might lead to the increase in glutathione and total thiol status and decrease in lipid peroxidation value in whole homogenate system. PMID- 1512016 TI - Absorption and fluorescence studies on interaction between cationic dyes and Klebsiella K7 capsular polysaccharide. AB - Interaction of cationic dyes, pinacyanol chloride, acridine orange and phenosafranin, with Klebsiella K7 capsular polysaccharide has been investigated by spectrophotometric and spectrofluorometric measurements. The acidic polysaccharide induce a metachromatic blue shift of the absorption band of pinacyanol chloride from 600 nm to 495 nm, indicating strong metachromasy. Stoichiometry of polyanion and dye cation (1:1.5) in the polymer-dye compound formed by the interaction between pinacyanol chloride dye and K7 polymer indicate that both glucuronic acid and pyruvic acid act as the potential anionic sites for interaction. Both spectrophotometric titration of pinacyanol chloride and spectrofluorometric titration of acridine orange and phenosafranin dyes by the polymer gave quite comparable equivalent weights for the polymer. Dye-polymer interaction studies indicated induction of metachromasy in the cationic dye by the anionic biopolymer, establishing its chromotropic character. PMID- 1512017 TI - Isolation and characterization of the haemolymph lipoprotein of desert locust, Schistocerca gregaria Forskal. AB - A yellow lipoprotein was isolated and purified from haemolymph of desert locust, Schistocerca gregaria Forskal, by precipitation at low ionic concentration and by gel filtration. Sephadex G-200 resolved haemolymph into five protein peaks. First peak was of lipoprotein with molecular weight of 501,000 +/- 7000 (n = 3) and on electrophoresis, it separated into three bands. Maximum lipids from lipoprotein could be extracted with chloroform: methanol solvent system and were 52% by weight. PMID- 1512018 TI - Location of chloroplast membrane resonances in high resolution 13C-NMR spectrum of spinach leaves. AB - Spinach leaves were studied by high resolution 13C-NMR spectroscopy. The spectra obtained, though highly complex, showed some distinct resonances assignable to carbons of lipids of the chloroplast membranes, thereby offering a novel way for studying the chloroplast membranes in situ. PMID- 1512019 TI - Effect of neonatal pineal ablation on estradiol receptors in mammary glands of rats housed under varying photoperiods. AB - Estradiol receptors (ER) in mammary glands of female Holtzman rats, either intact or neonatally pinealectomised and housed in 10:14 or 24:0 L:D (light:dark) schedule were studied at 30, 40, 50 +/- 5 and 65 +/- 5 days of age. Whereas ER were detectable only at the age of 60-65 days in intact rats housed in 10:14 L:D, they were present as early as 30 days onwards in the pineal ablated group. In the 24:0 L:D pinealectomised group, though mammary gland ER were maximum around 40 days of age and temporarily undetectable around day 50, they had stabilized around the age of 60-65 days. The data demonstrates for the first time, the modulation of ER in rat mammary glands in response to varying photoperiods as well as pineal ablation. Earlier reports on incidence of chemically induced mammary tumours have been compared to the receptor modulation. PMID- 1512020 TI - Aflatoxin B1 induced hepatocarcinogenesis in neonatal rats. AB - Role of cell replication on aflatoxin B1 (AFB1) induced hepatocarcinogenesis was investigated in neonatal rats showing persistence of cell replication in the liver for 21 days of post natal life. Adult (8-10 weeks old) rats displaying no hepatocytic proliferation served as controls. Three doses of AFB1 were administered to both the groups at intervals of 48 hr with the doses starting on 10th day of age in the neonatal group. Appearance of phenotypically altered preneoplastic hepatocytes was quantitated in both the groups. A significantly higher incidence of preneoplastic foci was recorded in neonatal rats as compared to adult animals. The results suggest that presence of cell replication in neonatal rats at the time of AFB1 administration enhances the process of hepatocarcinogenesis. PMID- 1512021 TI - In vivo growth inhibitory effect of Withania somnifera (Ashwagandha) on a transplantable mouse tumor, Sarcoma 180. AB - Withania somnifera is a medicinal plant used in the treatment of a variety of ailments in the Ayurvedic system. Alcoholic extract of the root of the plant was injected(ip) at daily doses of 200 to 1000 mg/kg body wt for 15 days starting from 24 hr after intradermal inoculation of 5 x 10(5) cells of S-180 in BALB/c mice. Solid tumor growth was monitored for 100 days. Doses of 400 mg/kg and above produced complete regression of tumor after an initial growth, the percentage of complete response (CR) increasing with increasing drug dose. A 55% CR was obtained at 1000 mg/kg drug administration, but this dose also produced some mortality among the animals. A significant increase in the volume doubling time and growth delay was seen when the drug dose was increased from 500 to 750 mg/kg body wt, but further increase in drug dose to 1000 mg/kg did not produce any significant increase in these responses. Cumulative doses of 7.5 to 10 g at daily doses of 500 or 750 mg/kg seems to produce a good response in this tumor. PMID- 1512022 TI - Late afternoon administration of melatonin is prosomatotrophic and exerts androgen independent effects on erythropoiesis in male house sparrow Passer domesticus. AB - In the third week of September 1989, birds were purchased locally and acclimated to their housing conditions in a room fully exposed to natural day length (average: 11.96 hr) and temperature (26 degrees +/- 2 degrees C) for 2 weeks. Birds were in the regressive phase of their annual gonadal cycle. In the first experiment 24 birds were selected randomly and were divided into 3 groups of 8 birds each. Initial body weight and bill color score were recorded. The birds of group-I and group-II were injected daily with 5 and 10 micrograms of melatonin in 0.1 ml of vehicle, respectively. The birds of group-III were injected with vehicle only and treated as control. Injections were given daily between 1700 and 1730 hrs over a period of 10 days. At the termination of the experiment, the birds were weighed, sacrificed, bill color scored, blood collected and immediately processed to determine the number of erythrocytes and hemoglobin concentration. The mean body weight loss amounted to 9.6% in vehicle-treated house sparrow. Birds receiving low and high doses of melatonin maintained their initial body weight. Melatonin significantly accelerated the rate of bleaching of bill color. Results clearly indicate that in house sparrow, melatonin produces prosomatotrophic and antigonadotrophic effects. The low dose of melatonin stimulated erythropoiesis significantly. In the second experiment, melatonin nullified the castration-induced decline in the number of circulating red cells. This clearly suggests that the influence of melatonin on erythropoietic machinery appears to be independent of testicular hormone(s). PMID- 1512023 TI - DNA polymorphism in Cab locus of tomato induced by tissue culture. AB - Plants were regenerated from callus induced from leaf disc explants of a tomato F1 hybrid heterozygous for three marker loci anthocyaninless (a), without anthocyanin (aw), and hairless (hl). Regenerants were studied for somaclonal variation at the phenotypic level by scoring for variation in the marker loci, and at the DNA level by probing geomic DNA blots with a chlorophyll a/b binding protein (Cab-3C) cDNA sequence. While no variation was observed at the phenotypic level in over 950 somaclones studied, DNA polymorphism for the Cab locus could be detected in two out of 17 somaclones tested. Tissue culture induced variation at the phenotypic level for specific loci is very low (less than 0.001 for a, aw or hl) but DNA sequence changes are induced at much greater frequency (approximately 0.1 for a multicopy gene family such as Cab). PMID- 1512024 TI - Effects of acute or chronic opioid agonists and their modulation by diurnal rhythmicity and satiety states on food intake in rats. AB - The effects of acute or chronic treatment with mu and k opioid agonists were investigated on food intake during light (0-6 hr) and dark (6-24 hr) phases in free fed and fasted rats. In free fed rats, morphine (MOR, 5 mg/kg, ip), a mu agonist, induced a hyperphagic response during both light and dark phases, whereas ketocyclazocine (KCZ, 1 mg/kg, ip), a k-agonist, enhanced food intake only during the light phase. Chronic MOR (x 7 days) produced a further enhancement of hyperphagia in the light phase and attenuated the dark phase response. Chronic KCZ, however, had opposite effects, i.e. tolerance to light phase hyperphagia and an enhancement in the dark phase response. In fasted rats, neither MOR nor KCZ appreciably enhanced food intake after acute administration but chronic treatment potentiated the acute opioid effects. These results are discussed in light of the role of diurnal rhythmicity, satiety states and receptor (mu and k) specificity/interactions in the opioidergic regulation of food intake. PMID- 1512025 TI - Correlative effects of quinidine on ECG pattern and serum cholesterol concentration in Acridotheres tristis. AB - Antiarrhythmic drug quinidine, administered daily at the rate of 10 mg/kg for 7 days in A. tristis produced an increasing effect on the amplitude and duration of different waves and intervals. Heart rate was decreased from 478.40 to 444.47 beats/min. Serum cholesterol level was reduced from 86 to 54.30 mg/100 ml. The data of the effect of quinidine on the ECG pattern and serum cholesterol were analysed and the values of the correlation coefficient and their significance were computed. The values of the correlation coefficient computed between the level of serum cholesterol (Y) and P-R interval (X) comes out to be significant at 5% level of significance. A linear regression line Y on X was fitted to the above data and the line is found to be: Y = 2535.897 X -62.858. This regression line may be used to determine the level of serum cholesterol on the basis of changes in the P-R interval of the ECG tracing in the quinidine treated birds. PMID- 1512026 TI - Nitroimidazoles, Part XXIII--activity of satranidazole series against anaerobic infections. AB - A large number of nitroimidazoles have been examined for in vitro activity against three anaerobes - Bacteroides fragilis (Bf), a strain of Bf resistant to metronidazole (16a) and Clostridium perfringens and many found to be active. Among these may be mentioned 1-methyl-5-nitroimidazoles carrying N - bound hetetocycles at position 2, such as satranidazole 1a, 1b, 1c, 1k, 1n and 1v which are at least twice as active as metronidazole (16a), ornidazole (16b) and tinidazole (16c). Even more active are 5-nitroimidazolyl benzimidazole 5d, thiazolidinone 6b and thiadiazolidine dioxide 8a. Many other types of compounds derived from 1-methyl-2-amino-5-nitroimidazole are feebly active. Among 5 nitroimidazoles with a carbon substituent at position 2, 16a, 16b and 16c are equiactive while dimetridazole 14f is more active than 16a against Bf. Some 2 vinyl derivatives are very potent, with 18f and 18i being outstanding. Activity better than that of metronidazole is seen for nitroimidazooxazepines, e.g. 29d. 5 Nitroimidazoles are more active against anaerobes than 4-nitro isomers. Antianaerobic and antiamoebic activities generally run parallel in these classes of compounds. The study has led to the elaboration of the antianaerobic profile of satranidazole 1a. PMID- 1512028 TI - Late effects of cyclophosphamide treatment of neonatal mice. AB - Swiss mice surviving early onset of wasting disease at 4-6 weeks following cyclophosphamide administration at birth suffer from delayed effects of this immunosuppressive drug. The late wasting syndrome developing at 6-8 months post inoculation is characterized clinically by loss of weight, hunched posture, ruffled fur and diarrhoea. Lymphocyte and granulocyte levels are raised. The lymphocyte/granulocyte ratio is significantly inhibited. The development of various pathological lesions in thymus, spleen, lymph nodes and bone-marrow is frequently observed. Infiltration of lymphoid tissue in lungs, liver and kidneys is a common feature. It is hoped that further experimental studies would provide more insight into the delayed adverse effects of cyclophosphamide therapy. PMID- 1512027 TI - Inhibition of cytokinesis by lead (Pb2+) in a centric diatom. AB - Effect of inorganic and organo lead has been studied on the mitosis of a centric diatom Cyclotella meneghiniana f. unipunctata. Binucleate cells were formed in the presence of different concentrations of Pb2+ (1.0, 2.0, 3.0 and 5.0 mM) due to inhibition of cell plate formation. Lead at 5.0 mM concentration was more inhibitory than the other concentrations. Organo lead was a powerful depressant of cytokinesis than inorganic lead. Failure of cytokinesis might be due to disruption of microtubules. Formation of distinct nuclei delayed post incubation cell divisions suggest partial damage of mitotic spindles. PMID- 1512029 TI - In vitro influence of hormones on transport of glucose and glycogen in liver and muscle of pinealectomised pigeons, Columba livia Gmellin. AB - To substantiate the increased peripheral utilization of blood glucose by pineal in wild pigeons, an in vitro study on the ability of liver and muscle slices of intact and pinealectomised wild pigeons (C. livia) in terms of uptake and release of glucose, and deposition and depletion of glycogen, in presence of insulin, acetylcholine, glucagon and adrenaline has been undertaken. A total insensitivity of liver and muscle of pinealectomised birds for glycogen deposition and insensitivity of liver for glucose uptake has been observed. Increased glucose release from liver in response to adrenalin has been observed. The results are discussed in terms of involvement of pineal in metabolic regulation associated with breeding activities. PMID- 1512030 TI - Effect of nicotine on glycosaminoglycan metabolism in rats. AB - Cigarette smoking has been established as a major risk factor for atherosclerosis and also for lung cancer. Nicotine is one of the major components of cigarette smoke which is believed to be partly responsible for the deleterious effect of cigarette smoke. There was significant alteration in the concentration of glycosaminoglycans (GAG) in rats exposed to cigarette smoke. Administration of nicotine to rats has been found to decrease many of GAG fractions in the aorta, liver and heart and increase in the lungs. The increase in GAG now observed in lung tissue in rats administered nicotine and those exposed to cigarette smoke may be involved in the increased incidence of lung cancer in smokers. Increased activity of many of GAG hydrolysing enzymes indicates increased degradation of GAG. Sulphate metabolism in the liver is also significantly altered by nicotine. Thus administration of nicotine to rats caused alteration in the metabolism of GAG which are similar to those observed on exposure of rats to cigarette smoke, indicating that nicotine content of the tobacco smoke may partly be responsible for the effect on GAG observed on exposure to cigarette smoke. PMID- 1512031 TI - Oocyte maturation in Clarias batrachus: in vitro effect of various gonadotropins and homologous pituitary homogenate. AB - The effects of five different gonadotropins and homologous pituitary homogenate (HP) on germinal vesicle breakdown (GVBD) were investigated in vitro using folliculated oocytes of Clarias batrachus. Among all the gonadotropins, salmon gonadotropin (SG-G100) was the most potent in vitro inducer of oocyte maturation. At concentrations of 1, 0.1, 0.01 and 0.001 microgram/ml it induced 86.98 +/- 2.71, 68.74 +/- 2.85, 44.56 +/- 1.75 and 25.90 +/- 2.36% GVBD. Next to SG-G100 in inducing GVBD was luteinizing hormone (LH) which was consistently found to be effective at all the concentrations used. Human chorionic gonadotropin was also found to be effective at all the concentrations but when compared to SG-G100 and LH, it was less effective. Follicle stimulating hormone and pregnant mare serum gonadotropin were found to be effective at higher concentrations but were ineffective at the lowest concentration. HP treatment resulted in a significant number of GVBD at all the three concentrations used. PMID- 1512032 TI - Effect of prolactin on accessory sex organs of prepuberal male albino rats: an in vitro study. AB - The in vitro studies on the effect of hypophysial gonadotropins (PRL, FSH, LH) on the maturation events of accessory sex organs in prepuberal male rats revealed that prolactin (PRL) alone has both direct as well as androgen mediated effect on the maturation activities. The effect of PRL is age dependent and it had higher activation on the gland system than the duct system. PMID- 1512033 TI - Salmonella typhi cell wall protein showing antigenic similarity to transferrin. AB - Antiserum to cell wall proteins of S. typhi showed immunoprecipitin lines of identity with homologous antigen, normal human serum and human transferrin. Also, anti-transferrin antibody showed immunoprecipitin band with S. typhi cell wall proteins and agglutinated S. typhi whole cells, but not Eschericia coli. It is speculated that transferrin or a transferrin-like protein present in the cell wall may play a role in iron-uptake by S. typhi. PMID- 1512034 TI - Reversal of endothelin-1-induced contractions by isoproterenol without myosin dephosphorylation in tracheal smooth muscle. AB - Effects of isoproterenol on isometric force, and 20,000 Da myosin light chain (LC20) phosphorylation were examined in smooth muscle fibre strips from lamb trachea stimulated with endothelin-1 (ET-1). ET-1 induced a rapidly rising isometric tension which was coupled with a multiple site phosphorylation of LC20. Isoproterenol addition at the time of peak isometric force resulted in a brisk relaxation of the fibre strips. Myosin light chain phosphorylation, however, remained unaffected. PMID- 1512035 TI - Fibrinolytic activity in bleeding associated with intrauterine contraceptive devices. AB - A prospective study was conducted to assess endometrial fibrinolytic activity before and after insertion of copper 250 (Multiload) and after removal of the IUCD. Fibrinolytic activity was measured on the fibrin plate in the form of zone of lysis. Sixty two women in the control group had fibrinolytic activity of endometrium in the range of 0.3-9.5 cm2 (mean +/- SD 1.77 +/- 1.27), 40 women who wanted to have the IUCD removed, because of reasons other than bleeding had a range of 0-9.5 cm2 (mean +/- SD 2.28 +/- 1.88) while 48 women who had the IUCD removed because of subjective menorrhagia had a range of 2.24-7.56 cm2 (mean +/- SD 4.75 +/- 1.20) which was higher than in the other two groups. PMID- 1512036 TI - Post-coital antifertility activity of the marine plant, Achrostichum aureum L. in rat. AB - The ethanolic extract of A. aureum and its fractions were evaluated for postovulatory antifertility activity in female rats. The water soluble fraction of ethanolic (95%) extract prevented (100%) pregnancy when administered to female rats on days 1-7 postcoitum. This fraction was found devoid of both estrogenic and antiestrogenic activities. PMID- 1512037 TI - Immunosuppression by human seminal plasma as evaluated by effect on natural killer cell cytotoxicity. AB - Re-examination of earlier observations of the suppressive role of oxidized polyamines and their cytotoxic products, has suggested that immunosuppression by seminal plasma (SePl) observed in in vitro assays employing culture medium supplemented with serum containing amine oxidase is 'artefactual'. Investigation of the relevancy of this suggestion to immunosuppression of natural killer (NK) cell activity by SePl as related to NK cell viability was made. NK cells in various culture regimens were preincubated in SePl and medium supplemented with 10 per cent foetal bovine serum, a source of amine oxidase, without and with 0.2 mM hydroxylamine, an amine oxidase inhibitor, and 10 per cent normal human AB serum, virtually devoid of amine oxidase, and examined for viability up to 72 h by trypan blue dye exclusion and lytic activity in a 4 h 51chromium-release microcytotoxicity assay. Viability to NK cells varied with the concentration of SePl, culture medium and time of incubation. At 18 and 24 h, times corresponding to preincubation and completion of the NK cell assay, viability was greater than or equal to 75 per cent for the optimum inhibitory concentration of SePl, irrespective of the culture medium. Comparison of the lytic activity of NK cells preincubated with the optimum inhibitory concentration of SePl in the various culture regimens did not disclose significant (P less than 0.05) differences.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1512038 TI - Socio-economic differentials in mothers at risk based on pre-pregnancy weights & heights. AB - Data on heights and weights of women measured as part of a longitudinal study on maternal and child health in Tamil Nadu state, south India are presented and discussed in relation to various socioeconomic and demographic factors. The mean (+/- SD) heights in rural and urban women were 151.2 +/- 5.4 cm and 150.8 +/- 6.6 cm respectively. The mean weights were 42.6 +/- 5.4 kg; and 44.0 +/- 7.9 kg respectively. The mean BMI were 18.6 +/- 2.2 and 19.4 +/- 3.5 respectively. The differences were statistically significant. Forty two per cent of rural and 48 per cent of urban women were less than either 145 cm in height or 40 kg in weight. The need to identify and care for such women as part of the "Risk Approach" in maternal and child health programmes is emphasized. PMID- 1512039 TI - Distribution of iodine in marine foods from different regions of India. AB - The iodine content of fresh and processed marine fish collected from different parts of coastal India was analysed. It was found that Indian marine fish are rich in iodine content (mean of 193 +/- 82 micrograms/100 g on wet weight basis). Also the iodine contents of shell fish and crabs (0.7-2.5 mg/100 g on wet weight basis) were higher than that of other fish. No significant regional differences were noted in the iodine content of marine fish. Further, no differences were observed in case of either salted or sun-dried fish indicating that curing did not influence the iodine content. PMID- 1512040 TI - Inhibition of aflatoxin production & growth of Aspergillus flavus by eugenol & onion & garlic extracts. AB - Efficacy of natural non-toxic materials including extracts of onion and garlic as well as eugenol was tested against aflatoxin production by A. flavus in liquid SMKY medium and in maize grains. Maximum inhibition in the mycelial growth occurred with garlic extract (61.94%), whereas inhibition of aflatoxin production was highest (60.44%) due to onion extract. Eugenol was most suitable for inhibiting aflatoxin production (60.35%) on maize grains. PMID- 1512041 TI - Peroxidative changes in experimental diabetes mellitus. AB - Changes in the levels of lipid peroxides and antioxidant enzymes were studied in male albino rats with experimental diabetes mellitus. Diabetes was induced by single subcutaneous injection of alloxan (19 mg/100 g body weight). The concentration of malondialdehyde (MDA) showed an increase both in the liver (P less than 0.01) and kidney (0 less than 0.05), while in the heart, there was a decrease (P less than 0.01), as compared to control values. A similar pattern of change was observed in the level of hydroperoxides in the liver and heart. The conjugated dienes showed an elevation during diabetes in all tissues (P less than 0.01). Glutathione levels in heart (P less than 0.01) and kidney were found to be decreased (P less than 0.05) while the liver showed an elevation during long-term diabetes (P less than 0.01). Serum ceruloplasmin showed an increase (P less than 0.05) in diabetes. Antioxidant enzymes superoxide dismutase and catalase decreased in all tissues (P less than 0.01) while the activity of glutathione s transferase increased in heart, but no change in other tissues. The studies thus show that lipid peroxidation is activated in liver and kidney while heart tissues show some resistance towards lipid peroxidation. PMID- 1512042 TI - Psychological assessment of blood related renal donors. AB - The impact of kidney donation on the psychological health of 31 living related donors was assessed by administering certain psychological tests before and after the operation (for donating the kidney). The results indicated a significant rise in the somatization subscale of the Middlesex Hospital Questionnaire (MHQ) from a mean of 1.61 to 3.23. There was no significant change in the other variables of these instruments or in the locus of control score. Only about one-fourth of the donors had prior knowledge of renal transplant. In almost all cases, the decision to donate had been voluntary and immediate, motivated by a concern for the recipient; there was virtually no second thoughts or regrets subsequently, which was apparently partly related to the opinions of other relatives who positively valued the act of donation. PMID- 1512043 TI - Antibiotics & glycosaminoglycan metabolism in rats. AB - The administration of antibiotics to rats resulted in significant alteration in the metabolism of glycosaminoglycans (GAG). The concentrations of the total GAG and most of the fractions increased in the aorta and liver in rats given tetracycline and cephalosporin, but decreased in ampicillin and streptomycin treated groups. The activity of biosynthetic enzymes of GAG in the liver increased significantly with all the antibiotics administered, except streptomycin. The pattern of change in the activity of many of the degrading enzymes of GAG in the liver and aorta was not uniform in different antibiotics administered groups. The changes observed in the activities of biosynthetic and degrading enzymes of GAG in the liver and aorta in different antibiotics administered groups may account for the alterations in the level of GAG observed in different experimental groups. PMID- 1512044 TI - Lipofuscin accumulation in ageing myocardium & its removal by meclophenoxate. AB - A study was undertaken on the age-associated histochemical changes in the ventricular myocardium and the influence of meclophenoxate hydrochloride (MPH) on the age pigment lipofuscin. Sixty Wistar albino rats in three age-groups (3, 15 and 30 months old) were treated with meclophenoxate hydrochloride (100 mg/kg body wt/day, ip) for a period of 2-8 wk. Five animals each from the three age-groups served as controls. Various histochemical and micromorphometric studies were carried out on the myocardial tissue. A linear increase in the myocardial volume occupied by the pigment was observed with advancing age. As a result of meclophenoxate treatment, a gradual decrease in the myocardial volume occupied by the pigment was noted. After 4-6 wk treatment, the pigment bodies were found lodged into the capillary endothelium and the lumen, facilitating the removal of the pigment via blood stream. Histochemical and micromorphometric analyses of ventricular myocardium of albino rats have shown thus that deposition of the age pigment, lipofuscin, can be accepted as an index of cellular ageing. PMID- 1512045 TI - Confidence intervals in medical research. AB - The utility of confidence intervals in a wide variety of situations in the medical field is re-emphasized, with examples drawn from controlled clinical trials, disease control programmes, vaccine trials and laboratory studies. It is shown that the confidence interval approach is more informative than a mere test of statistical significance, and should therefore be employed as an useful adjuvant. Since proportions are widely quoted in medical literature and as the determination of the exact confidence limits for a binomial proportion is iterative and time-consuming, an assessment is made of 15 published methods which provide approximate confidence limits; the 'Square root transformation' method is recommended since it is accurate and the computation of limits is relatively easy. In the case of a difference between two proportions, the usual method may be employed if sample sizes exceed 75; for smaller sample sizes (even for sizes of 5), the Jeffreys-Perks method is very satisfactory and is therefore recommended. PMID- 1512046 TI - Bacterial enteric infections and vaccine development. AB - There is a great need for effective vaccines against the major bacterial enteropathogens. Bacterial enteric infections resulting in diarrhea, dysentery, or enteric fever constitute a huge public health problem, with more than a billion episodes of disease and several million deaths annually in developing countries. Diarrhea caused by a bacterial enteric infection is also the commonest illness experienced by international travellers. Studies of pathogenesis have established the importance of specific ligand-receptor interactions between the enteropathogens and the intestinal epithelium, resulting in attachment and colonization of the bacteria and production of disease through either invasive mechanisms or production of toxins. Studies of protective immune mechanisms have emphasized the importance of secretory IgA antibodies and mucosal memory for protection against noninvasive, enterotoxigenic infections such as cholera and ETEC diarrhea and also drawn attention to the possible protective role of IFN gamma production by intestinal T cells in these secretory diarrheas. In invasive dysenteric and enteric-fever infections caused by such organisms as Shigella and Salmonella, optimal protection may depend on a combination of mucosal and systemic immunity. On the basis of this knowledge, several new vaccines have been developed and proved to be efficacious in large field tests. These include an oral killed B-WC vaccine and a killed WC-alone vaccine against cholera, and both a live attenuated oral vaccine (Ty21a) and an injectable Vi antigen vaccine against typhoid fever. In addition, a killed oral ETEC vaccine and live attenuated oral Shigella vaccines have begun to be tested in phase 1 and phase 2 studies in humans. The properties of the new vaccines against bacterial enteric infections give promise that these vaccines should be useful both in control programs in developing countries and for immunoprophylaxis against travellers' diarrhea. PMID- 1512047 TI - Cells and cytokines in mucosal immunity and inflammation. AB - The mucosal immune system consists of a number of compartments that are populated with a different assortment of cells and serve different functions. The cytokines produced by the cells in each of these compartments are currently being defined. This is best understood in relation to B cells, whose proliferation and maturation is guided by a sequence of cytokines. PP are inductive sites that preferentially stimulate IgA production. At least in part, this preference seems to be due to the T cells located in PP, which have been shown to stimulate switching to IgA production by cognate interactions and production of TGF-beta. Postswitch B cells expressing surface IgA respond to IL-5, a cytokine produced by T cells in GALT. Terminal differentiation to IgA-producing plasma cells in the lamina propria may be driven by IL-6, which can be produced by a variety of cells in the lamina propria and by epithelial cells. T cells in the lamina propria have an assortment of surface markers consistent with both activation and memory and appear to produce a variety of cytokines in the local environment that presumably act in normal host defense. IEL consist mainly of CD8+ T cells. They have been shown to produce IFN-gamma and, very likely, other cytokines that presumably act in a paracrine fashion on local enterocytes. How these cells and cytokines are perturbed during intestinal inflammation is currently being defined. A certain assortment of cytokines are greatly increased in IBD. This assortment, including IL-1, IL-6, and IL-8, is elevated in a wide variety of chronic inflammatory states in other tissues as well. A critical requirement for cytokines to exert their effects is the expression of specific receptors on target cells. Virtually nothing is known about this aspect of mucosal immunity, but receptor expression on mucosal cells must be defined before we will be able to understand the complex interactions among lymphoid cells, the cytokines they produce, and the local stromal and epithelial cells. PMID- 1512049 TI - Celiac disease. A gastrointestinal disease with environmental, genetic, and immunologic components. AB - In summary, research in immunogenetics, protein chemistry, and molecular biology is leading to a greater understanding of the contribution of genetic, environmental, and immunologic factors to the etiopathogenesis of celiac disease. Taken together, the findings discussed in this article suggest that understanding of the contribution of a major genetic factor to celiac disease susceptibility is closer at hand. Thus, the pathogenesis of celiac disease appears to involve an interaction between the gene products of the HLA class II D region on chromosome 6 and the gliadin proteins, possibly because of their homology with an intestinal viral protein. A logical extension of these findings would predict that T cells, particularly CD4 T cells, play a key role in the pathogenesis of celiac disease by virtue of their recognition of a gliadin or viral peptide in conjunction with the HLA class II D-region gene products. Nonetheless, the precise mechanisms by which the HLA class II genes and their products contribute to celiac disease is not known. Further, the precise peptide sequence in gliadin that interacts with the relevant HLA class II D-region molecule is not known. Finally, the role of CD4 T cells in the pathogenesis of celiac disease, either directly or indirectly by their ability to regulate other T-cell subsets and antibody-producing B cells, remains to be defined. The lessons learned and to be learned from celiac disease will substantially increase our understanding of the mechanisms that are important in this disease as well as in other intestinal and HLA-associated autoimmune diseases. PMID- 1512048 TI - The mucosal barrier, IgE-mediated gastrointestinal events, and eosinophilic gastroenteritis. AB - The "mucosal barrier" plays an important role in regulating immune responses in the gastrointestinal tract. Although the precise mechanisms controlling mucosal immune responses have not been defined, when an abnormal response such as IgE production is initiated, a variety of complex and incompletely understood pathophysiologic events occur and can result in gastrointestinal pathology. This article attempts to present the complexity of such abnormal responses. Although more questions have emerged than were answered, in recent years our knowledge of the pathophysiology of IgE-mediated events in the gastrointestinal tract has advanced significantly. Our understanding of the pathophysiology of these events will ultimately allow the development of more directed and effective therapeutic interventions for allergic gastrointestinal diseases. In addition, through further clinical and basic research, we should begin to unravel the more enigmatic conditions affecting the gastrointestinal tract, such as EG. PMID- 1512050 TI - Immune disorders of the liver and bile duct. AB - Several hepatobiliary diseases appear to be mediated by the host immune response. They can be subdivided into those in which the immune reaction is against an infectious agent such as hepatitis viruses, those in which the immune reaction appears to be against an autoantigen expressed on hepatobiliary cells, and those due to alloimmunity. The existence of autoimmune liver diseases indicates a breakdown in the mechanisms responsible for self-tolerance. In HBV infection, the hepatocellular necrosis appears to be mediated by the host immune response against viral antigens expressed on the membranes of infected hepatocytes. Autoimmune chronic active hepatitis can be subdivided on the basis of differences in circulating autoantibodies. In classic type I autoimmune chronic hepatitis, autoantibodies are directed against non-organ- and non-species-specific antigens. Thus, they are unlikely to be involved in pathogenesis. In contrast, type II autoimmune chronic hepatitis is characterized by antibodies against specific cytochrome P-450 isoenzymes that appear to be expressed on the surface membrane of hepatocytes. Immunogenic cytochrome P-450 also can be induced by drug metabolism and haptenation. This indicates that environmental or medicinal xenobiotics may initiate autoimmune liver damage. Primary biliary cirrhosis is characterized by T-cell-mediated inflammation and destruction of interlobular and septal bile ducts and antibodies specific for epitopes of the 2-oxo-acid dehydrogenase multienzyme complex of mitochondria. The histopathologic lesion NSDC also is observed in alloimmune-mediated diseases such as CGVHD and rejection of liver allografts. PSC may be mediated by an immune response against endothelial cells of the peribiliary capillary plexus, with secondary reactions to bile duct epithelial cell antigens. The pathogenesis of alcoholic liver disease is multifactorial, but one component involves an immune response to acetaldehyde-protein adducts. Secondary sensitization of cell-mediated effector mechanisms, endothelial damage, and secretion of noxious cytokines appear to be involved in pathogenesis. PMID- 1512051 TI - The role of the mucosal immune system in inflammatory bowel disease. AB - Continued delineation of the major factors that lead to intestinal inflammation will provide critical insights into many of the pathophysiologic events leading to tissue destruction in IBD. The exploration of exciting and important new areas, such as the role of adhesion molecules, proinflammatory cytokines, and the activation of lymphocytes and phagocytes, will contribute significantly to a better understanding of the mechanisms that sustain the intestinal inflammatory process. Determining the mechanisms of amplification and perpetuation of intestinal inflammation as well as learning more about the natural suppression of intestinal inflammation by the normal cellular and cytokine networks of the mucosal immune system will open exciting new therapeutic approaches. It is encouraging to see realistic and testable working models emerge from the combined efforts of many committed investigators who have been engaged in studying the role of the mucosal immune system in the pathophysiology of IBD. A great deal more remains to be learned in this rapidly advancing area, and we can look forward with confidence to continued advances in the study of IBD. PMID- 1512052 TI - Ambulatory blood pressure monitoring and circadian variation of cardiovascular disease; clinical and research applications. AB - Ambulatory blood pressure monitoring is an evolving technology. It has an established role in the diagnosis of hypertension, the clinical management of selected patients, and in the evaluation of new medication. From continuous recording much has been learned about the circadian nature of blood pressure and heart rate. Future research holds promise for a greater understanding of the mechanisms and treatment of cardiovascular disease. The purpose of this short review is to describe the development of ambulatory blood pressure monitoring, and outline some of its important contributions to date; and also to explore the research potential and clinical utility of advanced intravascular monitoring techniques, such as the continuous recording of pulmonary artery pressure in ambulant patients. PMID- 1512053 TI - Dynamic changes of the QRS complex in unstable angina pectoris. AB - Despite intensive medical treatment to control chest pain, about one-third of patients with unstable angina have an unfavourable outcome within a period of 1 to 2 months. Holter monitoring can identify patients with silent myocardial ischaemia that are at a high risk of sustaining a major cardiovascular event. The present paper describes the use of dynamic, continuous, computerized on-line vectorcardiography for real-time monitoring of QRS-complex and ST-segment changes in patients with unstable coronary disease. In many patients a pattern of frequent repetitive episodes of QRS change was observed, with or without concomitant ST change. Whereas no patient had episodes of ST-vector change without also having episodes of significant QRS change, 15 patients had several episodes of QRS changes without any episode of significant ST change. The number of episodes of significant increase of the QRS vector difference correlated weakly but significantly with the number of episodes of significant ST-vector magnitude change (r = 0.34, p less than 0.05). The present study suggests that myocardial ischaemia will influence the QRS complex as well as the ST segment. The mechanism behind the QRS changes observed is not clear but episodes of QRS change without ST change or chest pain, may reflect sudden depressions of left ventricular function, as has been reported by others to occur in patients with coronary artery disease. Dynamic vectorcardiography offers the opportunity to monitor all parts of the QRST complex in real time. PMID- 1512054 TI - Correlation of reciprocal ST-segment depression after acute myocardial infarction with coronary angiographic findings. AB - We studied 266 consecutive patients with acute myocardial infarction to assess the significance of electrocardiographic "mirror images". Ninety-four (group A) had anterior wall and 132 (group B) had inferior wall infarction. Thirty-one group A patients had stenosis of the right coronary artery greater than 85% in diameter (subgroup A1), and 63 either had a normal right coronary artery or less than 85% stenosis (subgroup A2). Of group B patients 62 had greater than 85% stenosis of the left anterior descending (subgroup B1) and 70 had a left anterior descending or less than 85% stenosis (subgroup B2). ST-segment depression was significantly greater in depth and duration in subgroup A1 than A2 (p = 0.02) and in subgroup B1 than B2 (p = 0.02, p = 0.01, respectively). Left ventricular ejection fraction was lower in subgroup A1 than A2 (p less than 0.001) and in B1 than B2 (p less than 0.001). There was a strongly positive correlation between depth and duration of ST-segment depression and the Gensini index (r = 0.78, 0.84) for anterior and inferior infarction, respectively. In conclusion, increased depth and duration of ST-segment depression opposite the infarct are indicative of ischemia, and are related to the extent of coronary artery disease, the degree of stenosis of the vessels supplying the opposite wall and of left ventricular dysfunction. PMID- 1512055 TI - Recombinant tissue plasminogen activator in acute myocardial infarction in the Chinese in Hong Kong. AB - Eighty-nine consecutive Chinese patients (69 males, 20 females) with acute myocardial infarction treated by 100 mg recombinant tissue plasminogen activator (7 intracoronarily, 82 intravenously) at 3.7 +/- 1.0 h after onset, and intravenous heparin or dipyridamole therapy started at 3 h, were studied prospectively. Their mean age was 59.6 +/- 10.6 yr. Forty-six patients (51.7%) had anterior and 39 patients (43.8%) had inferior infarcts. Clinical evidence of reperfusion were seen in 63 patients (70.8%), while new complications included hypotension (5.6%), heart failure (6.7%), cardiac arrhythmias (76.4%) majority of which are related to reperfusion and self-remitting, haematoma around vascular access sites (23.6%), melaena (3.3%) and cerebral infarction (2.2%). Maximal changes in coagulation profiles were seen at 3 h, including a decrease in fibrinogen by 64.2% and an increase in fibrin degradation products by 47 times. The changes in haemostatic variables were not related to body weight or bleeding complications. Nine patients (10.1%) had recurrence of angina and 6 patients (6.9%) died due to pump failure and reinfarction. Angiogram at 14 days confirmed TIMI 2 or 3 patency of infarct-related arteries in 63 out of 73 (86.3%) patients, with a mean global ejection fraction of 52.5 +/- 12.4%. Nearly all survivors could maintain class I-II functional status after discharge. The safety and promise of recombinant tissue plasminogen activator for acute myocardial infarction in the Chinese were confirmed. PMID- 1512056 TI - Ventriculoarterial coupling during exercise in normal human subjects. AB - To examine the relative roles of ventricular contractility and loading conditions for cardiovascular adjustment during exercise, 10 normal human subjects were studied using a framework of ventriculoarterial coupling. Anaerobic threshold was evaluated to determine the work rates of aerobic and anaerobic exercise. Ventricular contractile properties were quantified by the slope of the end systolic pressure-volume relationship (ventricular elastance) and arterial system properties were expressed by the end-systolic pressure-stroke volume relationship (arterial elastance). During aerobic exercise, left ventricular end-diastolic volume and stroke volume were increased by 14 and 33%, with plasma norepinephrine levels being doubled. Arterial elastance was reduced by 30%, but ventricular elastance did not change significantly. During anaerobic exercise, ventricular end-diastolic volume returned to the resting value, while stroke volume remained increased by 31%. In contrast to aerobic exercise, ventricular elastance rose substantially by 89% in association with about a 10 times increase in plasma norepinephrine. Arterial elastance remained the same as in aerobic exercise. Thus, the increase in stroke volume was primarily mediated by changes in loading conditions during aerobic exercise and by enhanced contractility during anaerobic exercise. PMID- 1512057 TI - Isolated right ventricular infarction. AB - The literature on isolated right ventricular infarction is reviewed and local experience is reported. Chronic lung disease is an important risk factor. Chest pain and breathlessness are common. Syncope and sudden collapse can also occur. Rhythm disorders include sinus bradycardia, atrial fibrillation and ventricular tachycardia or fibrillation. Atrioventricular block is rare. Hypotension and a right-sided fourth heart sound are common. Cautious use of slow-release nitroglycerin is not hazardous in the absence of hypotension. High doses of steroids and anticoagulants can be helpful. The prognosis is usually good, although sudden collapse can occur due to ventricular fibrillation, rupture of the right ventricular free wall or massive pulmonary embolism. PMID- 1512058 TI - Resting blood pressure and cardiovascular response to sympathetic stimulation in adolescents. AB - The prevalence of significant hypertension in childhood may be higher than expected. We have measured sitting blood pressure in 168 11-yr-old children attending a pre-high school in the Neapolitan area on four occasions over a 3 month period. We have also measured blood pressure and heart rate during a mental arithmetic test and during isometric exercise. Prevalence of significant hypertension (diastolic blood pressure 82-90 mmHg) was 13% at the first visit and decreased to 6.5% at the last visit; prevalence of severe hypertension (diastolic blood pressure greater than or equal to 90 mmHg) decreased from 5.4% to 1.2% from the 1st to the 4th visit. No sex-related difference was observed. A more frequently positive family history of hypertension (50% vs 30% in the fifth and first quintile of blood pressure, respectively) and higher body weight (body mass index = 21.4 vs 19.3 kg/m2) were found in children in the 5th quintile of blood pressure distribution. Blood pressure increased during mental arithmetic by 10/13% of the resting values in the first quintile and by 6/11% in the last one during mental test; during handgrip the increase was of 20/37% and 24/46%, respectively: differences between quintiles did not reach statistical significance. These data show that about 8% of a Neapolitan sample of school population have high blood pressure levels, while no difference in vascular reactivity to sympathetic stimulation was detected in children with higher blood pressure. PMID- 1512059 TI - The hypertrophied myocardium and coronary disease. Structural changes in patients submitted to aortocoronary bypass surgery. AB - Seventeen patients with coronary disease submitted to myocardial revascularization were studied. Ten patients had a hypertrophied ventricle, and 7 had normal ventricular mass. Myocardial biopsies were obtained before ischemia and at the time of reperfusion and were assessed for: volume fraction of fibrous tissue, myocyte diameter, morphometric mitochondrial studies and ultrastructural changes. The volume fraction of fibrous tissue in patients with hypertrophied ventricle was 1.9 +/- 0.04, and in patients with normal ventricular mass was 0.9 +/- 0.01 (p less than 0.05). The diameter of the myocyte was 23 +/- 0.3 microns and 18 +/- 1.2 microns for patients with hypertrophied and normal ventricular mass, respectively (p less than 0.01). The value of volumetric density for pre ischemia samples in patients with a hypertrophied ventricle was 23 +/- 2.2 and in patients with normal ventricular mass was 35 +/- 2.7 (p less than 0.02). Grades 3 and 4 of damaged mitochondria were significantly increased in reperfusion samples from patients with a hypertrophied ventricle compared to pre-ischemia samples. Collagen growth was increased in hypertrophied hearts which were also more sensitive to the ischemia/reperfusion mechanism. PMID- 1512060 TI - Stroke in coronary artery bypass graft surgery: an analysis of the CASS experience. The participants in the Coronary Artery Surgery Study. AB - An analysis of the Coronary Artery Surgery Registry (CASS) was performed to determine the occurrence of stroke after coronary artery bypass surgery in patients entered into the Coronary Artery Surgery Study Registry. Of the 10,098 patients having coronary artery bypass surgery at the Coronary Artery Surgery Study participating sites during the period July 1974 through May 1979, a total of 348 patients (or 3.4%) sustained a stroke during the first year after coronary bypass surgery. Fifty-nine strokes occurred on the day of surgery, and an additional 129 strokes occurred during hospitalization for coronary bypass surgery. Thus, 188 patients (1.9%) of the entire surgical group sustained a stroke during initial hospitalization for coronary artery bypass surgery. Logistic regression analysis was used to predict stroke on the day of surgery, during the hospitalization for surgery, and during the first year after surgery. The most powerful predictors of stroke on the day of coronary artery bypass surgery were: 1) older age (n = less than 0.0001); 2) use of alpha-adrenergic drugs after bypass (n = 0.0001); and 3) longer duration of cardiopulmonary bypass (n = 0.002). For those strokes occurring at least 1 day after coronary artery bypass but during the initial hospitalization, age and duration of cardiopulmonary bypass were the most powerful predictors of stroke. An analysis of predictors of stroke within 1 yr after hospital dismissal for initial coronary bypass surgery revealed that the most powerful predictor was a history of previous cerebrovascular disease (n less than 0.0001) and a history of hypertension (n less than 0.0001).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1512061 TI - Pacing termination of spontaneous ventricular tachycardia in the coronary care unit. AB - We reviewed our experience with the use of pacing techniques in the acute treatment of spontaneous ventricular tachycardia occurring outside the context of acute myocardial ischaemia. Over a consecutive 18 month period 23 patients (20 male, aged 38-76 yr) admitted to our coronary care unit experienced a total of 75 episodes of haemodynamically tolerated sustained ventricular tachycardia. Pace termination was attempted in 18 patients in a total of 58 episodes of ventricular tachycardia using a standard temporary external pacemaker. Pacing was successful in 32/58 (55%) attempts vs 13/49 (27%) with intravenous antiarrhythmic drug therapy p = 0.003. The superior success rate of pacing was apparent whether or not patients were receiving chronic antiarrhythmic drug therapy. Pace termination should be considered in the treatment of haemodynamically tolerated spontaneous ventricular tachycardias. PMID- 1512062 TI - Life-threatening pulmonary hypertensive crises occurring preoperatively. AB - A 10-week-old infant with left atrial isomerism and a primum atrioventricular septal defect presented with life-threatening episodes of collapse. They proved due to paroxysmal pulmonary hypertension, although her pulmonary artery pressure was virtually normal between attacks. The pulmonary hypertensive crises persisted early but resolved late after surgical correction. Labile pulmonary vascular resistance may prove a problem preoperatively if the ventricular septum is intact. PMID- 1512063 TI - Patency of Blalock-Taussig shunt assessed by Doppler colour flow imaging. AB - A neonate with pulmonary atresia and intact ventricular septum underwent a modified right sided Blalock-Taussig shunt. Following the procedure, the patient developed a right sided haemothorax, which required drainage. A murmur was not audible subsequently. Echocardiography with colour flow imaging enabled identification of patency of the right sided shunt. It was then possible to discontinue intravenous prostaglandin medication. PMID- 1512064 TI - Pericardial effusion as a result of cardiac rhabdomyoma. AB - A 34-yr-old patient is presented who suffered from chronic pericardial effusion. Surgical exposure revealed a right atrial rhabdomyoma. PMID- 1512065 TI - Are late potentials operative in arrhythmias following methylprednisolone pulse therapy. AB - We have evaluated 11 patients for the presence of late potentials in an attempt to investigate whether pulse methylprednisolone exerted its arrhythmogenic effect via this mechanism. All patients received pulse steroid therapy for their glomerulopathies. One of the patients developed bradycardia, no electrocardiographic abnormalities were present in the rest of these patients. Late potentials were not detected in any of the patients. Thus, in this preliminary study we have not been able to demonstrate that pulse steroid therapy plays a role in the genesis of late potentials. PMID- 1512066 TI - Successful coronary atherectomy during acute myocardial infarction. PMID- 1512067 TI - Post-operative left ventricular to right atrial shunt: detection by colour Doppler echocardiography. AB - A 24-yr-old man, who underwent combined mitral and aortic valve replacements for rheumatic valvar heart disease, was detected to have a left ventricular to right atrial fistula 3 months after surgery on routine cross-sectional and colour Doppler echocardiography. This complication of valve replacement is reported because of its rarity. PMID- 1512068 TI - Implantation of a dual chamber pacemaker in a patient with persistent left superior vena cava. AB - A patient underwent dual chamber pacemaker implantation by puncture of the left subclavian vein. During the procedure we observed persistence of the left superior vena cava. An active fixation atrial lead was required to prevent instability induced by the odd course of the electrode and produced excellent long term pacing and sensing. PMID- 1512069 TI - Perigraft seroma diagnosed by echocardiography: a complication following Blalock Taussig shunt. AB - Perigraft seroma is a specific clinicopathologic entity, which is a collection of clear, sterile fluid, confined within a nonsecretory fibrous pseudomembrane surrounding a vascular graft. Serous leaks and/or seroma formation from polytetrafluoroethylene grafts have been reported in peripheral arteriovenous anastomoses, arterial grafts and subclavian pulmonary anastomoses. We present a case of seroma formation which developed after a Blalock-Taussig shunt operation constructed with a polytetrafluoroethylene graft in a child with tricuspid atresia and which was diagnosed by echocardiography. PMID- 1512070 TI - Effects of MPTP and vitamin E treatments on immune function in mice. AB - The effects of treatment with the neurotoxin 1-methyl-4-phenyl-1,2,3,6 tetrahydropyridine (MPTP) and vitamin E, an antioxidant, on immune functions were examined. Male C57/B1 mice were fed daily with natural vitamin E for 12 weeks, subsequently injected i.p. with MPTP or its vehicle, and sacrificed 1 week later. Control mice received the stripped corn oil vehicle daily, in place of vitamin E. Oral vitamin E feeding increased cerebral vitamin E content by 60% (P = 0.05). However, MPTP attenuated this rise in cerebral vitamin E content when measured 1 week after treatment with the neurotoxin (P = 0.05). MPTP also produced an 80-90% reduction in striatal dopamine content in both the stripped corn oil control group and the vitamin E-treated group (P = 0.0000). One week after MPTP injection, the numbers of peripheral blood lymphocytes and the percent of spleen T-cells, but not B-cells, were decreased in those groups receiving MPTP alone or MPTP plus vitamin E (P less than 0.05 and 0.02, respectively). The Con A-induced IL-2 production of spleen cells was decreased in all treated groups (P less than 0.005). There was no difference in the mitogenic stimulative response to PHA, Con A or LPS. However, the response to PWM was increased in both MPTP and MPTP plus vitamin E-treated groups (P less than 0.05 and 0.001, respectively). On the other hand, the one-way mixed lymphocyte response of the splenocytes from the MPTP treated group was increased (P less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1512071 TI - Combined effects of selected insecticides on humoral immune response in mice. AB - Biological effects data with single insecticides are far more abundant than with mixtures. These data cannot be used directly to predict the effects of insecticide mixtures. Three insecticides of different chemical classes: organochlorine; dieldrin, organophosphate; malathion, and carbamate; carbofuran, previously evaluated for their immunotoxic potential, were selected for studies of combined acute exposure in C57B1/6 inbred mice. The humoral response to sheep red blood cells (SRBC) and the functional activities of peritoneal macrophages, such as phagocytosis of fluorescent beads and presentation of a single protein antigen, avidin, were examined after in vivo exposure of mice to different combinations of the selected pesticides and compared with the vehicle controls. Regarding exposure to single substances, the data confirmed the immunosuppressive potential of dieldrin and carbofuran and the immunopotentiating effect of malathion. Following the acute concomitant exposure to dieldrin/carbofuran mixture, however, values for the parameters of antigen presentation, primary IgM antibody response to SRBC antigen, and macrophage phagocytosis, returned to control or above-control values, indicating a lack of any synergistic or additive effects of the chemicals on the immune response. Thus, it was concluded the dieldrin/carbofuran mixture had an antagonistic effect on the humoral response to SRBC and the macrophage phagocytic activity, in comparison with the action of administration of each of the insecticides alone. PMID- 1512073 TI - Humoral responses following immunization with Leishmania infantum (ex. Oklahoma): a comparison of adjuvant efficacy in the antibody responses of Balb-C mice. AB - Adjuvants are commonly used in immunization protocols for the purpose of augmenting immune responses to antigens. The antigenic profile of Leishmania infantum (ex. Oklahoma) is described and the efficacies of three adjuvants delivered coincidentally with killed promastigotes are compared, by measuring relative serologic responses of Balb-C mice to specific antigenic determinants. Western blotting techniques were employed to visualize humoral responses to isolated antigens; serologic profiles were compared and contrasted. Four immunization protocols utilizing Freund's complete adjuvant, glucan adjuvant, lipovant adjuvant or phosphate-buffered saline, in conjunction with killed L. infantum (ex. Oklahoma) promastigotes were executed in parallel. All groups receiving adjuvant protocols developed enhanced serologic responsiveness. Similar profiles were observed in mice treated with glucan or lipovant. Animals receiving promastigotes in Freund's complete adjuvant also developed strong humoral responses, binding cross-reactive epitopes not recognized by other groups. Our findings indicate that glucan and lipovant present effective adjuvant alternatives, to Freund's complete adjuvant and may be of value in immunization against visceral leishmaniasis. PMID- 1512072 TI - IL-2 responsiveness of lectin-induced lymphoblasts: soluble IL-2 receptor release and differential in vitro effects of immunosuppressants. AB - We examined the mode of action of different immunosuppressants on the responsiveness of phytohemagglutinin (PHA)-induced lymphoblasts further stimulated by recombinant interleukin-2 (rIL-2). The stimulation of PHA blasts with rIL-2 resulted in an enhancement of tritiated thymidine ([3H]TdR) incorporation and of soluble interleukin-2 receptor (sIL-2R) release. Cyclosporin A (CsA) and prednisolone inhibited in different ways the responsiveness of PHA pre-stimulated blood mononuclear cells (PBMC) to rIL-2, as measured by [3H]TdR incorporation. The addition of CsA resulted in considerable enhancement of the release of sIL-2R, whereas the addition of prednisolone was associated with a similar enhancement only when the higher concentrations of rIL-2 were employed. EGTA, a calcium (Ca2+) chelator, and verapamil, a Ca2+ channel blocker, inhibited [3H]TdR incorporation in a concentration-dependent manner. EGTA inhibited sIL-2R release in the same manner when used alone, and reversed the CsA- and prednisolone-induced enhancement of sIL-2R release by rIL-2 induced lymphoblasts, when used in combination with CsA or prednisolone. Verapamil had a similar but less striking effect. The effects of CsA and prednisolone were also studied in PHA-induced blasts originating from purified CD4+ or CD8+ lymphocytes. Stimulation of these blasts with rIL-2 resulted in higher [3H]TdR incorporation by CD8+ blasts than by CD4+ blasts: however, no sIL-2R release was detected in supernatants of either CD4+ or of CD8+ blasts. Both CsA and prednisolone inhibited the rIL-2-induced enhancement of [3H]TdR incorporation by both T-cell subsets.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1512074 TI - Potentiation by thiopurines and sulfhydryl-reactive agents of the inhibition by 3 deazaadenosine of mononuclear phagocytes. AB - Combination effects of 3-deazaadenosine (c3Ado) on antibody-dependent phagocytosis in mouse resident peritoneal cells and human peripheral blood monocytes precultured with cytotoxic thiols, azathioprine (AZA) or 6 mercaptopurine (6-MP), and thiol-reactive agents, 2-cyclohexene-1-one (2-CH) or ethacrynic acid (ETA), are described. In the mouse cell preparations, a non inhibitory concentration of 10 microM AZA or 6-MP potentiated the inhibition by 5 and 10 microM c3Ado of phagocytosis. Higher concentrations of AZA or 6-MP (50, 100 microM) and c3Ado (40, 50 microM) were needed to achieve similar effects in human monocytes. Both 2-CH (50 microM) and ETA (25 microM) inhibited mouse cell phagocytosis and acted synergistically with c3Ado. Precultivation of mouse cells with an inhibitor of glutathione synthesis, buthionine sulfoximine (BSO, 50 microM) caused no inhibition of phagocytosis and no potentiation of the inhibition by c3Ado, although BSO potentiated the inhibition by 2-CH (50 microM). In human monocytes, non-inhibitory concentrations (10 and 25 microM) of gold sodium thiomalate (GST), AZA, and c3Ado, but not 6-MP, potentiated the inhibition by 2-CH (25-37.5 microM) of phagocytosis. Results are discussed in connection with the possible modulation by endogenous sulfhydryl-reactive metabolites of phospholipid turnover of the effects of c3Ado. PMID- 1512076 TI - Role of hydrolysis in the association of leu-enkephalin to peripheral blood mononucleate cells. AB - The possible hydrolysis of labelled leucine enkephalin in the presence of peripheral blood mononucleate cells and its association with the same cells have been investigated. Results obtained indicate that under experimental conditions leu-enkephalin is rapidly hydrolysed in the presence of model cells. Under the same conditions, the radioactive label is partially associated with the cells. The presence of protease inhibitors reduces both enkephalin degradation and association of the radioactive label with the cells. The hypothesis that the associated species is intact leu-enkephalin is not supported by the relative kinetics of enkephalin hydrolysis and of association of the radioactive label with the cells, nor by the statistically significant correlation between these data, nor again by the effect of proteolysis inhibitors. The same data agree with the hypothesis that the radioactive label associated with the cells is represented by one, or several, of the fragments formed by enkephalin hydrolysis, not by the intact molecule. However, results obtained in the presence of hydrolysis-stable DADL indicate association with the cells of the intact peptide. Moreover, antigen stimulation has opposite effects on the two peptides: with leu enkephalin, hydrolysis and association are increased, with DADL association is decreased by stimulation. The sum of these data seems to suggest the co-existence in PBMC of two phenomena, i.e. internalization of one, or several, of the fragments formed by the enzyme degradation of enkephalin and binding to membrane receptors of the intact pentapeptide. PMID- 1512075 TI - Enhancement of murine alveolar macrophage functions by orally administered beta glucan. AB - The effect of orally administered SSG, a beta-1,3-glucan obtained from the culture filtrate of the fungus Sclerotinia sclerotiorum IFO 9395, on alveolar macrophage (AM) functions of CDF1 mice was examined. SSG administered orally (20, 40, 80 or 160 mg/kg) for 10 consecutive days enhanced the lysosomal enzyme activity of AM. The greatest enhancing effect was observed at 80 mg/kg of SSG. Multiple oral administrations of SSG (10 consecutive days) were needed to induce significant enhancing effects. Phagocytic activity and interleukin-1 (IL-1) production of AM were also augmented by oral administration of SSG, and the kinetics of the activated state differed depending on the kind of activity. However, H2O2 production of AM was not affected by SSG. Orally administered SSG also (40 or 80 mg/kg, 10 consecutive days) increased the number of AM and the greatest increment was observed 14 days after the first administration. On the other hand, the supernatant of Peyer's patch (PP) cells from mice administered SSG (80 mg/kg) orally stimulated the lysosomal enzyme activity of AM in vitro, and enhanced colony stimulating activity (CSA) was detected from this supernatant. These results demonstrate that SSG given by the oral route can activate murine AM both qualitatively and quantitatively, and it would mediated, at least in part, by the activation of PP cells in the intestine. PMID- 1512077 TI - Model of bronchial allergic inflammation in the brown Norway rat. Pharmacological modulation. AB - Exposure of non-sensitized Brown Norway (BN) rats to a 10%-ovalbumin aerosol induced an increase in the number of neutrophils in the broncho-alveolar lavage (BAL) fluid 3 and 6 h later but with no change in number of cells at 24 h. When the BN rats were actively sensitized (i.m. injection of 10 mg/kg ovalbumin and i.p. injection of killed Bordetella pertussis) and exposed 12-14 days later to a 10%-ovalbumin aerosol there was an increase in the number of eosinophils in the BAL fluid, maximal 24-48 h after the anaphylactic reaction. The increase in the number of neutrophils in the bronchial lumen 3 and 6 h after the anaphylactic reaction was larger than that obtained in non-specific inflammation and in contrast to this was still present 24-48 h after ovalbumin exposure. In passively sensitized BN rats exposed to ovalbumin aerosol, no inflammation appeared in the BAL fluid 24 h after the anaphylactic reaction. Various drugs, administered twice, 5 min and 5 h after the anaphylactic reaction, have been evaluated for their effects on the 24-h inflammation obtained in actively sensitized rats. Dexamethasone acetate (0.08 mg/kg i.p.) and theophylline (50 mg/kg i.p.) decreased the number of eosinophils and neutrophils. Ketotifen fumarate (12.5 mg/kg), cetirizine dihydrochloride (12.5 mg/kg), salbutamol (2 mg/kg), disodium cromoglycate (50 mg/kg) all given intraperitoneally, reduced the number of eosinophils. Tioxamast decreased the number of eosinophils at 12.5 mg/kg i.p. and by the oral route.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1512078 TI - Improvement in the proliferative capacity and natural killer cell activity of murine spleen lymphocytes by thyrotropin. AB - In the present study we investigated the effect of thyrotropin (TSH) on both the proliferative capacity and the natural killer (NK) cell activity of murine spleen lymphocytes. It was found that TSH at various concentrations significantly increased the proliferative response of mouse lymphocytes to both concanavalin A (Con A) and phytohemagglutinin (PHA). This increase was particularly evident when suboptimal concentrations of mitogens were used (40-50% increase). The administration to cell cultures of TSH alone could not induce a significant stimulation of proliferative capacity. In order to provide a better knowledge about the mechanism by which TSH improved the mitogen-induced lymphocyte proliferation, the effect of the pituitary hormone on lymphocytes directly stimulated with recombinant interleukin-2 (RIL-2), was examined. It was observed that there was a great increase in IL-2-induced lymphocyte proliferation by TSH. The improvement in proliferative capacity of lymphocytes was particularly evident by using suboptimal rIL-2 concentrations (25-30% increase). The studies carried out on the cytotoxic activity of NK cells showed that TSH was able to significantly increase the IL-2-induced NK cell activity without modifying the basal levels of cytotoxicity. The results support the immunoregulatory role of TSH and contribute towards understanding the mechanisms of interaction between neuroendocrine and immune systems. PMID- 1512079 TI - Modulation of IgM to IgG class switch by protein A. AB - The Fc binding property of soluble protein A (SpA) from Staphylococcus aureus has been utilized to form IgG-SpA complexes which enabled an increase or decrease of IgG from the host depending on the dose of SpA administered. When 5 micrograms SpA was administered the IgG-SpA complexes were rapidly catabolized and, hence, low plasma IgG levels were observed. In contrast 25 micrograms SpA resulted in a significant increase in the IgG level in the host plasma. Based on these observations, the present investigation attempted to study the effect of IgG depletion/increase on the primary and secondary B-cell response to sheep erythrocyte (SRBC) antigen in Balb/c mice. Introduction of 5, 10 and 25 micrograms SpA at the time of the primary antigenic challenge inhibited both the primary IgM and the secondary IgM and IgG responses in a dose-dependent manner. Administration of 5 and 10 micrograms SpA at the time of the secondary antigenic challenge enabled the host to maintain the otherwise depressed secondary IgM response equivalent to the normal primary response. In contrast, 25 micrograms SpA at the time of the secondary antigenic challenge inhibited both the IgM and IgG PFC responses. These results extend our understanding of the mechanism of switch in immunoglobulin class expression during antigen driven maturation of the B-cell response. PMID- 1512080 TI - Increased oxidative metabolism in PMA-activated lymphocytes: a flow cytometric study. AB - Flow cytometry and the fluorescent dyes DCF and R123 were used to examine oxygen metabolite production in human leukocytes and T-lymphoblastoid Jurkat cells, activated by PMA or by FMLP. When unseparated leukocytes were activated by PMA, oxidative products were generated not only in PMN and monocytes but also to a lower extent in lymphocytes. These responses were correlated with protein kinase C activation. PMA did not, however, induce the synthesis of reactive oxygen species in isolated lymphocytes. FMLP did not affect lymphocyte oxidative metabolism when added to the whole leukocyte mixture, but activated only the phagocyte populations. Similarly, Jurkat cells which alone were unresponsive to PMA, became strongly fluorescent when they were mixed with PMN and treated with this activator. In all cases, they did not respond to FMLP. Superoxide dismutase and catalase addition did not prevent the lymphoid cell response in the presence of phagocytes, whereas Desferal did. These data indicate that under physiological conditions, activated lymphocytes are capable of oxidative metabolism and also evidence some close relation between the leukocyte populations. We discuss the putative mechanism of oxygen metabolite generation in lymphocytes and the role of these metabolites in the immune response. PMID- 1512081 TI - In vitro effects of retinoid RO 10-9359 on lectin-induced activation and proliferation of T-lymphocytes. AB - RO 10-9359 has been shown to cause a dose-dependent (0.05-50 micrograms/ml) inhibition of proliferation of rat thymocytes after in vitro activation by PHA and Con A. In experiments designed to dissect the effects of the drug on various aspects of proliferation it was demonstrated that RO 10-9359 did not inhibit IL1 production by macrophages, nor the IL1-dependent events of T-cell activation, i.e. the IL2 production and the acquisition of IL2-receptors. However, the capacity of exogenously supplied IL2 to stimulate the proliferation of T-cells that had previously acquired IL2-receptors was suppressed by RO 10-9359 in a dose dependent manner. Thus, it appears that retinoid RO 10-9359 does not interfere with the early events of T-cell activation, but inhibits lectin-induced proliferation by affecting the later phase of proliferative activity after T-cell triggering. PMID- 1512082 TI - Tumor-specific L3T4+ and Lyt-2+ lymphocytes in mice primed to mutagenized cell variants. AB - We have investigated the tumor-specific reactivity of different T-cell subsets from mice primed with clonal variants of L5178Y and P815 cells treated with N methyl-N'-nitro-N-nitrosoguanidine (MNNG). In both tumor systems, anti-parental tumor immunity and protection against non-immunogenic clones were only induced by vaccinating the hosts with highly immunogenic cell variants, and the effect correlated with the detection of TATA-specific delayed-type hypersensitivity (DTH) reactions. The footpad reaction was transferable with spleen cell populations from immunized mice, and enrichment of splenic lymphocytes in L3T4+ but not Lyt-2+ lymphocytes increased the footpad swelling. Unfractionated spleen cell populations from immunized mice released high amounts of IL-2 and IFN-gamma in vitro in response to parental antigens. Purified L3T4+ and Lyt-2+ lymphocytes also produced IFN-gamma when incubated in vitro with the parental tumors and accessory cells. It is suggested that the mechanisms of anti-parental tumor immunity induced by MNNG-treated variants may be similar to those described previously for triazene-xenogenized L5178Y/DTIC cells, and may involve induction of a tumor-specific DTH reaction and IFN-gamma-mediated stimulation of non specific tumoricidal effects. PMID- 1512083 TI - In vitro effects of three iron chelators on mitogen-activated lymphocytes: identification of differences in their mechanisms of action. AB - The effects of three iron chelators (ADR-529/ICRF-187; omadine/pyrithione; and a newly synthesized pyridoxal-based iron chelator, SAG-15) on cultured BALB/c murine lymph node cells stimulated with phorbol myristate acetate and ionomycin have been investigated. All three agents were found to inhibit [3H]-thymidine incorporation after 66-72 h incubation. Pretreatment of ADR-529 and omadine with Fe(III) or Fe(II) ions did not prevent their inhibitory effects. However, pretreatment of SAG-15 with Fe(II) or Fe(III) ions led to a significant increase in the ID50. Time-course studies of cell viability and thymidine incorporation demonstrated that the inhibitory effect of omadine was attributable to cell killing while for ADR-529 and SAG-15 there were both cytostatic and cytotoxic effects. Cell cycle analysis showed that treatment of cells with ADR-529 led to arrest in G2/M while treatment with SAG-15 led to a G0/G1 arrest. Iron has an obligatory role in T-lymphocyte activation that may be related to the formation of reactive oxygen species. SAG-15 is a new iron chelator that will help in the elucidation of the precise role of iron in lymphoproliferation. Since SAG-15 is an extremely effective iron chelator in vivo it has potential as an immunosuppressive agent. PMID- 1512084 TI - Immunosuppression induced by non-reducing acylated monosaccharide subunits of lipid A. AB - Synthetic acylated glucosamine monosaccharides, representative of the non reducing subunit of lipid A, were compared for their ability to induce non specific suppression of antibody forming cells. Five of nine analogs were found to be functional in this respect, indicating that these compounds, carrying a phosphate at C4 and acyl substituents at C2 and C3 are the smallest synthetic analogs of lipid A capable of eliciting non-specific immunosuppression. A comparison of the analogs inducing suppression with those testing negative revealed that (i) a single 3-hydroxymyristoyl group at C2 is common to 4/5 analogs inducing suppression; (ii) addition of an oxytetradecanoyl group to the 3 hyroxymyristoyl group at either C2 or C3 negated suppression; and (iii) extreme specificity was exhibited in suppression induction such that substitution of either lauric (C12) or palmitic (C16) for myristic acid (C14) at C2 voided transmission of the suppressive signal. PMID- 1512085 TI - Physiologic skin changes associated with pregnancy. PMID- 1512087 TI - Cutaneous sarcoidosis. PMID- 1512086 TI - Lichen planus and lichen planus-like eruptions: pathogenesis and associated diseases. PMID- 1512089 TI - Mudi-chood: an unusual tropical dermatosis. AB - Mudi-chood is an unusual dermatosis seen in India. It affects the nape of the neck and the exposed part of the upper back in girls and young women. It is characterized by mildly pruritic pigmented papular lesions. It probably represents the comedogenic activity of various oils applied to the hair, which is aggravated by the typical climatic conditions. We present three cases of mudi chood. PMID- 1512088 TI - Lichen planus and the liver. PMID- 1512090 TI - Basal cell carcinoma in tropical Australia. AB - A survey of people with skin cancer in tropical Australia detected a change in site of the prevalent cancer. In the post-war generation more basal cell carcinomas are occurring on the back and fewer on the head and neck. A reversal of the sex ratio was also detected, with more women being afflicted. PMID- 1512091 TI - Post-kala-azar dermal leishmaniasis in the Sudan: peripheral neural involvement. AB - Four patients developed post-kala-azar dermal leishmaniasis and neuritis (PKDL) 1 to 6 months following apparently successful treatment of kala-azar. The duration of the lesion varied between 1 month and nearly 5 years. The lesions were macules, papules, or nodules affecting the face, extremities, and trunk. The diagnosis was made by demonstration of the parasite in slit smear and biopsies and by a positive direct agglutination test (DAT). Histologically, the patients were found to have neuritis affecting the cutaneous nerves in the lesion only. The nerves showed a lymphohistiocytic infiltration and occasionally parasites. There was no impairment of sensation. Response to sodium stibogluconate was good. PKDL may simulate leprosy both clinically and pathologically. PMID- 1512092 TI - Liver biopsy versus ultrasound in methotrexate-treated psoriasis: a decision analysis. AB - Before starting methotrexate therapy for cases of recalcitrant psoriasis, a liver biopsy has been usual in order to exclude cirrhosis and moderate or severe fibrosis, which are contraindications for methotrexate treatment. As mortality and morbidity of liver biopsy are not negligible, and as this invasive procedure is unpleasant for the patient and urges clinical admission, we evaluated the possibility of ruling out severe liver pathology by means of ultrasonography, which we compared to liver biopsy. We made this comparison by means of a decision tree. The advantages of this analysis are the clear definition of the decision problem and its alternatives, and the possibility of calculating the risk of each alternative, thus being able to choose the best diagnostic method. In this study, the results of various research groups are discussed, in which liver biopsy and liver ultrasound were compared. In our decision tree we used some of these results and other assumptions, based on comparable studies. We varied the biopsy mortality and the sensitivity of ultrasound to show the change in the risk of each alternative. Our analysis shows that the differences of expected values between the liver biopsy branch and the ultrasonography branch are relatively small. Therefore, we advise each center, which has at its disposal a specialist in liver ultrasonography, to re-evaluate its guidelines with regard to the detection of severe liver pathology before starting methotrexate for the treatment of psoriasis. PMID- 1512093 TI - Immunohistochemical identification of Penicillium marneffei by monoclonal antibody. AB - We present an experimental study on the immunohistochemical identification of Penicillium marneffei in paraffin-embedded, formalin-fixed tissue. The monoclonal antibody EB-A1 detects a specific galactomannan that appears to have at least one epitope identical in P. marneffei and Aspergillus sp. This immunohistochemical approach could be useful in the diagnosis of a rare diseae, penicilliosis marneffei, which proves to be difficult to identify by conventional microscopy. PMID- 1512094 TI - Melasma-like (pigmented) actinic lichen planus. AB - Four patients suffering from pigmented actinic lichen planus were studied. Clinically, the lesions are melasma-like, affecting mainly the face and exacerbating in summer and spring time. The histopathologic and immunofluorescence studies showed typical changes of actinic lichen planus. The possibility of pigmented actinic lichen planus should be considered in every patient with facial melanosis. PMID- 1512095 TI - Worldwide strategy for skin health care in a financial strait-jacket. AB - In consideration of the year 2000, dermatologists must take up the challenge of "Health for All." This paper draws attention to the scope of dermatology, the nature of its work force, the qualifications that are desirable, and the deficiencies and impediments that characterize dermatologic solutions worldwide. It suggests that the future of dermatology depends on achieving appropriate and essential staffing, technology, drugs, and learning materials, within available financial resources. To achieve this, dermatologists must talk more persuasively to those who govern and some centralization of resources into regional training centers may be desirable. Delegation of skin care to purpose-trained auxiliaries, nurses, or medical assistants is essential if costs are to be contained while enlarging the work force. PMID- 1512096 TI - Nodular (keloidal) scleroderma. PMID- 1512097 TI - Multiple myeloma presenting as migratory panniculitis. PMID- 1512098 TI - Primary thymic carcinoma and its association with dermatomyositis and pure red cell aplasia. PMID- 1512099 TI - Eosinophilic cellulitis (Wells' syndrome). PMID- 1512100 TI - Euthyroid pretibial myxedema. PMID- 1512101 TI - Eccrine hidradenitis. PMID- 1512102 TI - Porphyria cutanea tarda in an HIV-infected patient. PMID- 1512103 TI - Occult syringoma associated with alopecia. PMID- 1512104 TI - Kaposi's sarcoma following renal transplantation. PMID- 1512105 TI - Ofloxacin versus cephalexin for treating skin and soft tissue infections. AB - Patients with acute localized skin or soft tissue infections were randomized to receive either ofloxacin (300 mg orally, b.i.d.) or cephalexin (500 mg orally, b.i.d.). Among 401 enrolled patients, 382 were evaluable for safety and 148 for microbiologic response. Microbiologic cure occurred in 93.4% of ofloxacin-treated patients and in 94.0% of those treated with cephalexin. Clinical cure or improvement, respectively, was found in 85.2% and 11.1% of patients treated with ofloxacin, and 83.6% and 14.9% of patients receiving cephalexin. Adverse effects (primarily associated with the gastrointestinal tract and central nervous system) were considered to be drug-related in 7.9% of those receiving ofloxacin and 4.8% of those receiving cephalexin. Thus, ofloxacin is as effective and well tolerated as cephalexin and a good alternate antibiotic for treating skin and skin structure infections caused by a variety of pathogens. PMID- 1512107 TI - Primary exudative ascites in systemic sclerosis. PMID- 1512106 TI - Henry Radcliffe Crocker, M.D., F.R.C.P., (1845-1909), physician to the Skin Department of University College Hospital. PMID- 1512108 TI - Reflections on developments in the theory of psychoanalytic technique. PMID- 1512109 TI - Psychic change: insight or relationship? AB - The phenomenon of psychic change has been a subject of interest since the beginning of psychoanalysis. The author presents clinical material from a four year analysis of a 50-year-old man, including a verbatim session, which illuminates two questions raised about psychic change. (1) What criteria may be used to evaluate psychic change and how do those criteria relate to the concept of 'structural change'? (2) Is it insight or the effects of a new object relationship that is most responsible for the changes that a patient is able to achieve? The search for a single mechanism of psychic change is doomed to frustration. But the author argues that insight is crucial to psychoanalytic change, both for its own sake and for its role in maintaining an understanding relationship. PMID- 1512110 TI - Psychic change and its clinical evaluation. AB - The author looks at the question of psychic change from the viewpoint of difficulties involved in this change, starting with a short historical overview. He discusses 'the difficult patient as a specialist in resisting change' and describes the clinical characteristics of such patients over and above their psychopathological diagnoses. Some specific clinical cases are described to clarify the theoretical ideas. The author then covers the nature of changes best studied within the field of transference and countertransference. Finally, he examines change as a process of change and suggests that qualitative differences exist between psychic functions relating to 'traumas' in narcissistic constraints. These differences are apparent in psychic content. The connexions between interpretation, insight, anxiety and change are described. The nature of the negative therapeutic reaction is discussed. The notion of an underlying deficiency in the development of genuine egoistic resources required to bring about psychic change is examined. PMID- 1512111 TI - Some changes observed in a clinical case. AB - The author presents clinical material from a 36-year-old female patient with depressive and hysterical traits, whose personal history shows her psychosexual development to be at a pregenital level. It is intended to demonstrate the type of clinical interpretations that enabled a change towards an oedipal transference in order to reach a psychoanalytic approach. Some of the psychoanalytic interpretations during the treatment process are described, related to several behavioural changes and a discrete structural change. PMID- 1512112 TI - Marc, or the solder's journey. The elaboration of passivity as a factor of change. AB - Change during analysis is here understood as the possibility of elaborating the 'biological bedrock' described by Freud as the repudiation of femininity in both sexes. The analysis of a man with anxiety hysteria permits us to show how temporal regression induced by the analytic setting enables the elaboration of passivity in its fantasy and object-related aspects. The return of this patient seven years after the end of the analysis in a moment of strange coincidence for the analyst, gave rise to a consideration of the difficulties and the issues in topographical and formal regression during analysis: the necessity of working on the dynamics of the narcissistic double and on the anxieties relating to the danger of non-representation and the loss of the capacity for investment. The working through of this primordial passivity, corresponding to active work, concerns analyst as well as analysand in their common work and constitutes the final point which all analyses should reach to achieve a durable change in its topographical, dynamic and economic aspects. PMID- 1512113 TI - Psychic change: some perspectives. AB - I have not attempted in this paper to discuss psychic change in general, nor the aims of change as such, but rather an approach to achieving psychic change. I discuss the way in which both patient and analyst bring into the analytic relationship their own way of looking at things, their own vertex, and how the converging and separating out of these vertices is part of the movement within the analytic relationship, in the session, where it is experienced by both participants and is basic to the stuff of insight and to psychic change. PMID- 1512114 TI - Psychic change: development in the theory of psychoanalytic techniques. 37th IPA congress overview. AB - This paper addresses some of the methodological problems in assessing and understanding change in psychoanalysis, including the twin difficulties of not knowing precisely what transpires in an analytic session and not knowing to which of the many aspects of psychoanalytic process any particular change should be assigned. There are alternate models for understanding change. The most commonly used model is that of psychoanalytic growth with the analyst acting as a fostering maternal figure. An alternate model of change is of psychic repair with the analyst in a more physicianly role. Analysts also work with alternative models of trauma. In one model danger stems from the infant's own overwhelming affective states, while in the other model danger comes from parenting failures. Analysts also differ regarding the importance assigned to interpretation and insight rather than to the new relationships and altered experience. This paper elaborates these models and their implications for psychoanalytic technique and our understanding of psychic change. PMID- 1512115 TI - From technique to a theory of psychic change. PMID- 1512116 TI - Psychic change: the analytic relationship(s) and agents of change. AB - Psychic change, the agents of change, and the theory of technique have gradually changed pari passu with other changes in the field. Rather idealized concepts of structural change have been supplanted by current emphasis on experience-near clinical and functional change. There are varied processes and agents of change, but interpretation and insight are crucial to psychoanalysis. Attention to noninterpretive agents of change includes contemporary theoretical and technical interest in the analytic relationship(s). As analyses become much longer, the real relationship expands, and may impede the analysis of inter-weaving transference and countertransference ramifications. The ambiguous concept of 'new object' primarily refers to the analyst's analytic attitude, role, and analysing functions. Analysis progresses with internalization of the analytic process, but internalization of the analytic relationship and experience may also contribute to psychic change. The analyst should have a stable analytic attitude and identity, and be able to change with new knowledge and experience. PMID- 1512117 TI - Psychoanalytic contributions to Holocaust studies. AB - The purpose of this presentation is to provide a comprehensive overview to a wide audience of how effects of trauma incurred by victims of Nazi persecution during the Holocaust may affect survivors and their children. In doing so, one has to accept that powerful defences employed by survivors themselves and the world about them led to a 'latency period' which delayed investigation of the late sequelae of Holocaust trauma. Bridging the gap was stimulated by the passage of indemnification legislation by the Federal German Republic which enabled mental health professionals to investigate these possible effects. Psychoanalytic theories of trauma had to be reconsidered in the light of these inquiries. Further study revealed that the effects of massive and cumulative trauma may be transmitted to the second generation. Recurrent themes and conflicts in children of survivors have been described. Clinical illustrations have been provided to illuminate some aspects of problems encountered in treating members of a traumatized group. Finally, issues involving unresolved mourning and questions of commemorating the Holocaust have been considered. PMID- 1512118 TI - Does psychoanalysis heal? A contribution to the theory of psychoanalytic technique. AB - Beginning with Freud's controversial admonition to psychoanalysts to model themselves on the surgeon who 'dresses the wound, but does not heal it', the author attempts to explore the limits of the therapeutic effect of psychoanalysis. After briefly reviewing the role of projective identification in the transference, and the origin of the analyst's need to be a healer in his anxieties about the strength of his own destructive impulses, he describes certain emotional difficulties that arise in the analyst when he accepts the fact that he can only do analysis. He goes on to suggest that, while psychoanalysis is able to reduce the psychic distance between parts of the patient's mind that have been separated by splitting, this in itself does not provide the patient with a corrective emotional experience, mitigate the severity of his superego, or guide him along the correct developmental path. He further suggests that the analyst's acknowledgement of this limitation--which is equivalent to acknowledging that he can help the patient to grow, but he cannot 'grow' him--is part of a state of mind that the analyst must have to do analysis, and that this state of mind helps to distinguish the practice of psychoanalysis from that of other psychotherapies. PMID- 1512119 TI - Inductive reasoning in clinical psychoanalysis. AB - It is argued that clinical observations can be used to test psychoanalytic theories. Psychoanalysis cannot use controlled experiments but it can use the standard canons of inductive reasoning to test the reliability of conflicting theories. Conflicting hypotheses concerning narcissism and object relations are analysed to identify crucial observations that can be used for testing. If these experiments in theory testing are reliable they show that psychoanalysis is not limited to being a hermeneutic discipline but rather has legitimate claims to be a natural science. PMID- 1512120 TI - Psychic change in child analysis. AB - The paper describes a period of analysis of a 5-year-old boy as an illustration of some ideas about psychic change. Psychic change is approached in terms of emotional growth, which is directly associated with the degree of flexibility of the defensive system and its capacity to absorb and re-integrate lost parts of the ego and to be open to new emotional experiences. It is described how, through interpretations, the child's internal objects and relationships changed. In particular, his representation of his bad-analyst, bad-father, bad-self changed from being a gorilla to the Incredible Hulk to the whale and finally to Superman crying. When the analysis was interrupted, the patient was showing clear indications that the basis had been laid for establishing a more stable internalized object capable of containing and transforming his anxieties and feelings of despair into more tolerable ones, which gave him a better chance of being fed by good experiences. PMID- 1512122 TI - Psychic change in the analyst. AB - This paper addresses the use of one's mother tongue as a means of facilitating access to splitoff regions of the mind. It also looks at the different situation of strong emotional impact for the analyst which requires, upon recognition, careful reflection and analysis in order to separate the analyst's own transference from the counter-transference. The latter is taken as the total of all the analyst's reactions towards what the patient is and what he/she brings into analysis. PMID- 1512121 TI - Psychic change and developments in the theory of technique in adolescent analysis: the handling of perverse levels of transference. AB - The paper presents some of the characteristics of the analytic process in an adolescent with homosexual behaviour. The technical peculiarities of this kind of treatment are compared with those of adult patients with similar pathologies. The difficulties arising from complex acting-out behaviour in which the family take an active part, the role of secrecy, and the handling of the erotization of the transference through the verbal interchange are discussed on the basis of the clinical material presented. The characteristics of a strongly split transference, with a dissociated perverse level, imply specific difficulties in maintaining a workable analytic setting; the strategic choices with which the analyst is faced to be able to attain it, and its clinical implications are discussed. PMID- 1512123 TI - Ambiguity as the route to shame. AB - In patients who have been exposed to extreme conditions, shame is connected with a dilemma of identity: it is indicative of the patient's conflict over his alienation, his adaptation to and familiarization with the conditions offered by an unacceptable frame. Bleger's (1967) theoretical model, with the concepts of the symbiotic link, ambiguity and the ambiguous position (which precedes the classical Kleinian positions), dynamically combines the problem of the frame or context with that of the capacity of discrimination between the ego and its objects. Ambiguity is characterized by the adaptability, malleability, permeability and non-conflictuality which it confers on the personality. Shame appears as an alarm signal concerning ambiguity, connected with the ego's need to maintain its internal conflictuality, its capacity for integration and its sense of continuity. Experiences of dependence and passivity, or ones which touch upon the dilemma between true and false, private and public, ethics and aesthetics, etc., may give rise to feelings of shame. In this paper it is suggested that a common denominator for the many different factors of shame may be found in the dynamics of ambiguity. PMID- 1512125 TI - Countertransference: the analyst's retreat from the patient's vantage point. AB - As analysts, we may agree with certain basic tenets: we should not impose our truths, whether or not theory-laden; we should maintain the focus on the patient's inner reality, not on how he or she lives in the world--out there; we should be prepared to be surprised, to learn something that hadn't occurred to us; we should look for multiple cues in the clinical data, pay attention to affect and state as may be expressed within the moment, and listen for subtleties that may convey something about how we are being experienced in the transference. But again and again, we fail to adhere to these precepts. Despite our best intentions, we seem to have a fundamental disinclination to maintaining these positions. I have tried to consider some reasons for this difficulty and its relation to the countertransference. Drawing upon several clinical examples, I have attempted to examine ways of enhancing our attunement to verbal and non verbal cues from the patient which may direct us, sooner, to dimensions of our counter-transference responses otherwise overlooked. PMID- 1512126 TI - The autistic-contiguous position. PMID- 1512124 TI - An anatomical commentary on the concept of infantile oral sadism. AB - Although this paper is entitled 'An anatomical commentary on the concept of infantile oral sadism' it is also an attempt to examine hypotheses regarding the sources of oral sadism. Freud did not explicitly refer to an oral sadistic phase of development in early infancy, believing as he did that sadism was a component instinct. Abraham postulated that oral sadism arises when the teeth erupt and the jaw muscles function. Melanie Klein, however, came to claim that oral sadistic impulses operate from birth and arise from the infant's innate potential for fantasy. This hypothesis is akin to Freud's theory of primal fantasies. The anatomical record supports Abraham's theory of the source of oral sadism. PMID- 1512128 TI - [Sampling limitations in studies of primary care: comparison of 4 sampling designs]. AB - Different sampling methodologies have been used to avoid the great amount of information which arises in Primary Health Care. The objective of this study is to compare the estimates of four sampling schemes, analyzing variables of utilization, referral activity and diagnostic morbidity, based on data obtained from consultations in a health centre over a one-year period. The percentage of error between each sample estimation and the real value for the whole data set was obtained. Sampling schemes using week periods showed the worst results (40% of error in the estimation of chronic consultations, 18% of error in the percentage of radiology requests and more than 13% in the estimation of morbidity). The findings of this study suggest that some of the sampling schemes usually applied in primary care studies have important limitations, showing the need for more research in this field. PMID- 1512127 TI - [Prevalence of dental caries among school children: a cross-sectional survey in the city of Barcelona]. AB - The results of a cross-sectional survey performed in the spring of 1990 in a sample of 533 twelve-year old schoolchildren in the city of Barcelona (Spain) are presented. The proportion of children with caries is 49.2%, with a DMFT index of 1.34 (1.09 for boys and 1.50 for girls). 63.4% of permanent decayed teeth were filled, and 2.2% were missing. There is a socioeconomic gradient in dental decay, with more caries among the lower socioeconomic strata, where missing teeth concentrate. The comparison of these results with those of other studies suggests a decline in caries incidence in school age in Spain, and greater use of dental care services. PMID- 1512130 TI - [Meta-analysis in epidemiology (2): quantitative methods]. AB - The main goal of this paper is to offer an introduction to the quantitative methods of meta-analysis used in epidemiology/public health, emphasizing on the most widespread used. We give also a brief reference of the methods to recognize publication bias. The limitations and advantages of the methods commented on are discussed. PMID- 1512129 TI - [Prevalence of tobacco consumption in Mallorca]. AB - The prevalence of tobacco consumption has been estimated in the population of Mallorca, by means of a survey based on interviews of a random sample of 300 individuals between the ages of 18 and 75, selected from the 1986 electoral census of the Island. From the 297 valid questionnaires, the prevalence of smokers was 34%; 15% were ex-smokers and 50% non-smokers. Among women younger than 40 years old the prevalence of smokers was 60%. A direct relationship between level of education and prevalence of smokers was observed for women. Immigrants from the mainland of Spain formed a major proportion of smokers (44%) compared to the Mallorcans (30%), and also among those living in the main city (41%) with respect to those living in other areas (25%). The prevalence of tobacco consumption in Mallorca shows a similar pattern to that of other geographical and cultural areas with similar characteristics. PMID- 1512131 TI - [Should general practitioners consider the costs of their prescriptions? Reflections stemming from the "White Paper" and an opinion survey]. AB - The British government proposal to introduce drug budgets will compel general practitioners to consider the financial consequences of prescribing. In our country, the practitioner neither in the past nor now has an incentive to consider the cost of his prescription, and few efforts have been made to influence it, if we exclude the pharmacy industry. In the present article, the situation of both countries is analyzed and the answers of the general practitioners of Girona and Scotland to questions that examine their predisposition towards considering costs when prescribing are compared. The reduction of the prescription costs must be formulated as a part of a rational prescription and should employ a combination of approaches: education, feedback, administrative changes, and incentives. The procedures to encourage a more efficient use of medicines require an active participation of the practitioners in managing the resources of their practices. PMID- 1512132 TI - [Differential mortality by sex in Catalonia]. AB - The purpose of the study is to analyse the evolution of sex differentials in mortality rates in Catalonia (Spain), to assess which causes of death have the higher differentials and to compare the results with other countries. Standardized mortality rates (direct method), sex mortality ratios and differences were obtained. Mortality data refers to 1985 to allow for comparison. Men had higher mortality than women, for cancer, accidents and diseases of the digestive tract. Women had higher mortality rates for endocrine diseases, mental disorders, cardiovascular, skin and muscle-skeleton diseases and ill-defined causes. The evolution in recent years shows a relative stabilization after an increasing trend observed from 1960 to 1979. In general, men had a 60% higher than women age-adjusted mortality rates in the four countries to which Catalonia is compared. Suicide and accidents showed the highest sex mortality ratios. Diabetes showed a different ratio in Catalonia and Spain (higher female mortality rate) compared to other countries. The causes of death with higher male mortality were accidents, as well as causes associated with smoking (lung cancer and ischemic heart disease). PMID- 1512133 TI - Induction of invasive and experimental metastasis potential in BALB/c 3T3 cells by benzo(a)pyrene transformation. AB - A clone of BALB/c 3T3 cells (A-31), which is highly resistant to spontaneous in vitro transformation, was treated with the carcinogen benzo(a)pyrene [B(a)P]. This agent was capable of inducing in vitro transformation in the presence of S9 activating system and 6 weeks after treatment large foci were detected. Transformation frequency in solvent control groups was very low. Three foci from a single plate of two different experiments were pooled and the cells tested for their in vitro invasive properties and in vivo tumorigenic and metastatic potential. B(a)P-transformed 3T3 cells grew in soft agar and were highly tumorigenic when injected s.c. in nude mice (75% incidence within 7 weeks). Untreated cells were poorly tumorigenic (0/4 mice had tumors within 7 weeks), though they also gave rise to neoplasms after a longer latency. Spontaneous metastasis incidence was low for both controls and treated cells; however, almost all animals (15/16) injected i.v. with B(a)P-transformed cells had pulmonary nodules in the experimental metastasis assay. A few nodules in some of the animals in the control group were detected (4/16). B(a)P-transformed cells were able to invade a thin coating of matrigel in the chemoinvasion assay and also grew in matrigel showing an invasive, branching morphology. Untreated cells did not grow or invade. Our data suggest that a single treatment with a chemical carcinogen can increase tumorigenicity as well as confer invasive and experimental metastasis potential in BALB/c 3T3 cells. This work provides evidence for a role of chemical carcinogens in tumor progression. PMID- 1512135 TI - Endothelial injury causes degradation of adjacent basement membranes and promotes their invasion by A549 carcinoma cells. AB - Experiments in vivo have demonstrated that endothelial cell injury promotes the local arrest of circulating, intravascular cancer cells and the subsequent formation of metastatic tumors. The experiments described here were performed to test the hypothesis that injury of the endothelium also causes damage to the adjacent vascular basement membrane, which in turn facilitates the passage of cancer cells across the vessel wall. Confluent monolayers of bovine pulmonary artery endothelial cells were incubated with 3H-2-deoxyglucose or 3H-proline to label the endothelial cells or the basement membrane, respectively. After adding H2O2 to these cultures, damage of the endothelium and basement membrane was detected by release of the isotopes into the culture medium. The kinetics and magnitude of basement membrane degradation correlated with the damage to the endothelial cells. Evidence for involvement of endothelial proteases in basement membrane injury included identification of a 63-kD gelatinase in the culture medium, inhibition of injury by protease inhibitors and the inability of H2O2 to cause 3H-proline release when applied directly to basement membranes. Scanning electron microscopy demonstrated that a greater number of A549 lung adenocarcinoma cells attached to the basement membrane and endothelium at points of endothelial retraction. However, this was not due to an increase in the adhesive properties of the basement membrane. The media from injured endothelial cultures stimulated the motility of A549 cells in a Boyden chamber assay. Furthermore, in a 24-hour invasion assay, a greater number of A549 cells migrated through injured basement membranes than through control membranes. We conclude that endothelial cell injury can cause enzymatic damage to the underlying basement membrane and postulate that this can facilitate the transvascular passage of cancer cells in vivo. PMID- 1512134 TI - Invasion in vitro of malignant hamster brain tumor cells is influenced by the number of cells and the mode of malignant progression. AB - We investigated the capacity of two glial tumor cell lines (CxT24neo3 and CxT3Cl5) to invade through reconstituted basement membrane (Matrigel, MG). The purpose of our experiments was to establish whether the number of cells or the mode of malignant progression would quantitatively modify the invasion of a brain tumor cell population. To accomplish this goal, we used a vital-dye method to assess the fraction of cells that invaded through 30 micrograms MG coated on a polycarbonate filter (8 microns pore size). Our experiments demonstrated that the fraction of invasive CxT24neo3 and CxT3Cl5 cells in vitro reproducibly differed as a function of the number of initially seeded cells. This showed that invasion through MG was subject to quantitative changes caused by the number of cells present. Since CxT24neo3 and CxT3Cl5 became malignant by transfection with different oncogenes, the results also indicated that the type of quantitative change was influenced by the mode of malignant progression. PMID- 1512136 TI - Legible medical records. PMID- 1512137 TI - Psychological management of obesity. PMID- 1512138 TI - Beware the 'quick and easy' diet. PMID- 1512139 TI - Coronary disease prevention should begin in childhood. PMID- 1512140 TI - A nutritionist discusses obesity. PMID- 1512141 TI - Clinically severe obesity--a review. AB - Gastrointestinal surgery is indicated for some severely obese patients. These two experts discuss guidelines for evaluating potential candidates. PMID- 1512142 TI - Community-based CME. PMID- 1512144 TI - The American Society for Histocompatibility and Immunogenetics. 18th Annual Meeting Abstracts. October 16-21, 1992, Kansas City, Missouri. PMID- 1512143 TI - Syncopal episodes: reducing future risks. PMID- 1512145 TI - The radiation dose-response relationship in a human glioma xenograft and an evaluation of the influence of glutathione depletion by buthionine sulfoximine. AB - We have used an extensively characterized human glioma cell line in an athymic mouse model to evaluate new therapeutic approaches for human supratentorial high grade gliomas. The tumor, D-54MG, is a subline of a human anaplastic glioma. Eight days after homozygous nu/nu BALB/c athymic mice received intracranial (IC) injections of a tumor homogenate, the whole brain was irradiated with either single fractions of 4, 8, 9, and 12 Gy or twice daily fractions, separated by least 6 hr, of 2.28 Gy x 2 or 7.53 Gy x 2. To evaluate whether or not glutathione depletion influenced animal survival, animals at each dose level received either intraperitoneal (IP) buthionine sulfoximine (BSO) alone or I.P. BSO plus BSO in the drinking water. There was a stepwise prolongation of animal survival with increasing doses of external beam radiation. Mean survival in 9 of the 10 control groups (8-12 animals per group) ranged from 14.1 to 18.8 days. Mean survival ranged from 15.3 to 22.5 days at 4 Gy, 25 to 30 days at 8 Gy, 22.3 to 29.7 days at 9 Gy, and 32.9 to 33.6 days at 12 Gy single dose irradiation. At 2.28 Gy x 2 split dose irradiation mean survival was 29.3 days, for 7.53 Gy x 2 mean survival was over 47 days. The data for single fraction irradiation fit a linear regression line (r = 0.908) of mean animal survival = (1.22 [dose in Gy] + 16.7) days. Tumor GSH levels were decreased with all BSO dosing regimens tested. The most aggressive regimen (I.P. BSO+oral BSO for 5 days), reduced tumor GSH to 6.2% of control. Increased survival in irradiated glutathione depleted mice versus mice receiving radiation alone was not seen. PMID- 1512146 TI - Quantitative comparison of radiolabeled antibody therapy and external beam radiotherapy in the treatment of human glioma xenografts. AB - Using 90Yttrium radiolabeled antibodies, radioimmunotherapy was compared to fractionated external beam radiotherapy in the treatment of human glioma xenografts. Antibody treatments required administration of an approximately threefold greater total dose compared to external beam treatments to achieve the same tumor regrowth delay. Following multi-fraction external beam radiation treatments, tumor regrowth delay demonstrated a large fractionation effect (alpha/beta = 2.3 Gy, 95% confidence limits 0.4-4.2 Gy), suggesting that much of the ineffectiveness of the antibody treatments could be caused by a large dose rate effect in this system. Despite the large fractionation effect, the regrowth delay was small for a large single-fraction external beam irradiation, possibly because of tumor hypoxia. When compared to external beam radiation, radiolabeled antibody treatments resulted in a comparatively diminished tumor bed effect, suggesting radioimmunotherapy spares normal tissue surrounding the tumor. PMID- 1512147 TI - Radioresponsiveness, sublethal damage repair and stem cell rate in spheroids from three human tumor lines: comparison with xenograft data. AB - Dose-control curves after fractionated irradiation were generated for small oxic spheroids from the two human glioma cell lines, U87 and A7, as well as the squamous cell carcinoma line FaDu. These data were fitted by the linear quadratic model assuming Poisson statistics. The alpha/beta values of A7, U87, and FaDu spheroids, respectively were 10.3 (8.1-12.9) Gy, 17.8 (15.1-21.1) Gy, and 37.9 (29.1-51.5) Gy. These data were compared with those previously published by Suit et al. (31) and Zietman et al. (40) for 6 mm xenografts of U87 and FaDu after fractionated irradiation and for A7 after single dose irradiation under clamped conditions. A good agreement in the alpha/beta values was observed for U87 and Fadu xenografts and spheroids assuming an oxygen enhancement ratio (OER) of 2.7. In addition, the ranking according to the single doses needed to control 50% of the tumors agreed for xenografts and spheroids from the three cell lines. U87 was the most resistant line in both model systems, followed by A7 and FaDu. However, the absolute values of alpha and beta, obtained from the direct fit to the dose control data were only about half as high for U87 and FaDu xenografts than for the spheroids. Monte Carlo simulations showed that this discrepancy can be explained by a greater tumor heterogeneity of the xenografts. While the number of critical stem cells or spheroid rescuing units equaled the number of cells per spheroid for the three cell lines, the percentage of tumor rescuing units for Fadu and U87 xenografts was estimated to be below 1%. In a next step, survival curves were generated for exponentially growing cells of the three lines. A7 cells were significantly more radioresistant when plated on tissue plastic than in soft agar. Using the most resistance-promoting colony assay conditions for each cell line, a good agreement was observed for the alpha and SF2Gy values calculated from the colony and spheroid control data. This study shows that the spheroid model can quantitatively predict the repair capacity of sublethal damage as well as the rank order of radiation sensitivity of in vivo tumors. PMID- 1512148 TI - Comparisons of the efficacy of 186Re- and 131I-labeled antibody in multicell spheroids. AB - Several radionuclides are being studied for use in radioimmunotherapy. Although 131I has been used most widely, there are several disadvantages to it including its large gamma-ray component, its rather long half-life, and its modest beta particle energy. However, the beta-particle energy can be an advantage in very small tumors (less than 1-2 mm). 186Re has several potential advantages over 131I but it has never been directly compared with it experimentally. Dosimetry modeling predicted that 186Re would have a dose advantage over 131I at large tumor sizes but for tumors as small as 1 mm diameter, this advantage would be lost. In order to confirm these predictions experimentally, this study compared the relative efficacy of a pancarcinoma antibody, NR-LU-10 labeled with 186Re or 131I in 0.8-1.0 mm diameter LS174T human colon adenocarcinoma multicell spheroids. Spheroids were incubated for 90 hr at 37 degrees C and evaluated with clonogenic assay, autoradiography, and histology. When corrected for cumulative activity bound, both radionuclides were equally effective. Autoradiography demonstrated poor penetration of radionuclide into the depths of the spheroids. Because 186Re has a theoretical dose advantage in larger tumors and because it has been shown to be equivalent to 131I in tumors as small as 1 mm diameter, it may be superior to 131I in most clinical situations. However, in the treatment of micrometastases of less than 1 mm diameter, theoretical dosimetry modeling predicts that 131I or radionuclides with similar beta particle energies should be more effective. PMID- 1512149 TI - The influence of neonatal thymectomy on the development of radiation myelopathy in rats. AB - To investigate the possible contribution of cellular immunity in the development of radiation injury of the central nervous system, Wag/Rij rats were thymectomized at birth and irradiated to the cervical spinal cord at the age of 3 months. At the time of paralysis or at the end of the follow-up period (when rats were 1-year-old) the animals were sacrificed and the mediastinum was examined histologically. In 95% of the neonatally thymectomized animals no thymus was left. These rats showed a firm impairment of the cellular immunity, as they had a 40% reduction of the T-lymphocytes in the spleen, and a 70% reduction of the mixed lymphocyte reaction, compared to age-matched controls. Both single dose and two-fraction irradiation experiments were performed. No modification of the latency time to develop paralysis was observed comparing thymectomized and age matched controls. The incidence of foreleg paralysis after cervical spine irradiation (single dose or two-fraction) was identically distributed in the follow-up period for both neonatally thymectomized and control Wag/Rij rats. The ED50 value derived in the single dose experiments was 20.3 Gy for the control animals, and 20.9 Gy for thymectomized rats, and in the two fraction experiments 29 Gy for controls and 29.6 Gy for thymectomized rats. None of these differences are significant. It appears that neonatal thymectomy, in spite of its firm suppression of the cellular immunity, has no major influence on the development of radiation myelopathy in rats. PMID- 1512150 TI - A reliable method for quantitating chromatin fragments by flow cytometry to predict the effect of total body irradiation and hyperthermia on mice. AB - The frequencies of chromatin fragments, including micronuclei, in murine thymus cells, spleen cells and bone marrow cells have been used as a quantitative indicator of gamma-ray induced chromosome damage and could be used to screen potential radioprotective agents as well. The yield of chromatin fragments induced in mice receiving different dosage levels of total body irradiation alone and in mice also given whole body hyperthermia as a potent radioprotector were assessed by flow cytometric analysis. Our results demonstrated that chromatin fragments induced by irradiation in vivo was clearly dose-dependent and that chromatin fragments could potentially serve as a biological indicator of radiation damage. One hour of whole body hyperthermia at 40 degrees C (+/- 0.2 degree C) given 20 hours before a lethal dosage (900 cGy) of total body irradiation protects 100% of DBA/2 mice from an LD 100/16 irradiation dose (dose of irradiation that killed 100% of the mice in 16 days). This is in good agreement with the percent of chromatin fragments formed in the cells of the protected animals, which showed no significant difference from those observed in the normal mice. The results indicate that whole body hyperthermia protected the thymus and bone marrow from irradiation damage. This study provides further evidence which supports that whole body hyperthermia can act as a potent radioprotector in vivo. Measurement of the frequencies of chromatin fragments by flow cytometry is simple and reliable. The method can be applied to screen radioprotective agents. PMID- 1512151 TI - Combined hyperthermia and irradiation in the treatment of superficial tumors: results of a prospective randomized trial of hyperthermia fractionation (1/wk vs 2/wk). AB - From December 1984 to December 1989, 240 superficially located recurrent/metastatic malignant lesions (173 patients) were enrolled in a prospective randomized study of one versus two hyperthermia fractions per week. In the majority of patients, the dose of radiation therapy was less than 4000 cGy over 4 to 5 weeks. Stratification was by tumor size, site, and histology. The goal of the hyperthermia sessions were 42.5 degrees C for 45-60 min minimum intra tumor measured temperature. Hyperthermia was given after radiation within 30-60 min. External applicators, both microwave (over 90% of treatments) and ultrasound, were used. Overall, complete response rate in 222 evaluable lesions was 56.3% (125/222) with a minimum follow-up of 6 months and a maximum follow-up of 52 months. The complete response rate for once a week versus twice a week hyperthermia group was 54.7% and 57.8%, respectively. The severe complication rate was 18% (41/222). There was no difference between the two treatment arms. Cox regression analyses were performed to study the prognostic significance of patient characteristics, tumor characteristics, and treatment parameters. Detailed analysis and results are presented. PMID- 1512152 TI - Dysgerminoma of the ovary: good prognosis even in advanced stages. AB - Dysgerminoma is a rare germ cell tumor of the ovary. It constitutes about 0.5% of all ovarian malignancies. During a 12-year period (1978-1989), 22 patients were treated at the National Cancer Institute, Cairo, Egypt. According to the FIGO classification system, 4 patients were allocated to Stage I, 2 were Stage II, 13 were Stage III, and 3 were Stage IV. The 5-year actuarial survival rate for all patients was 76%. Conservative treatment in addition to retrieval therapy upon recurrence could achieve 100% survival rate in Stage I patients. Surgery followed by irradiation resulted in a 66% 5-year actuarial survival rate in Stage III and 67% in Stage IV. Retroperitoneal lymph nodes seemed to have a better survival than peritoneal tumor extension. The adoption of an elective irradiation policy to the mediastinum and supraclavicular area seemed to have a good influence on prognosis. However, the extent of surgery performed could not be shown to affect survival. PMID- 1512153 TI - A new re-entrant ionization chamber for the calibration of iridium-192 high dose rate sources. AB - A re-entrant (well-type) ionization chamber has been designed and fabricated at the University of Wisconsin for use with iridium-192 high dose-rate (HDR) remote after-loading brachytherapy devices. The chamber was designed to provide an ionization current of about 10(-8) ampere with a nominal 10 curie iridium-192 source. A narrow opening is provided into the sensitive volume of the chamber to insert a Nucletron MicroSelectron catheter, or catheters with similar diameters from other HDR manufacturers. The chamber exhibits a flat response (+/- 0.1%) for any source position within +/-4 mm of the chamber center. A 300 volt chamber bias yields a 99.96% ion collection efficiency. The chamber is capable of being calibrated directly with an iridium-192 source which has in turn been calibrated with thimble-type ion chambers. Reproducibility for readings in the current mode for 10 consecutive insertions of the MicroSelectron iridium-192 HDR source is within 0.02% or less. Two thimble chambers calibrated by the U.S. National Institute of Standards and Technology provide calibration traceability of iridium 192 HDR sources and re-entrant chambers to a primary national standards laboratory. Results of activity measurements of 6 commercial iridium-192 HDR sources are reported. PMID- 1512154 TI - The effect on dose of kilovoltage x-rays backscattered from lead. AB - Dose enhancement on the backscatter side of a soft tissue/high Z material interface is known to exist for megavoltage x-ray beams. Caused by an increase in backscattered electron fluence, the enhancement persists for short distances upstream of the interface, equal to the range of these electrons. Since photon interaction cross sections are small, there is little photon backscatter at these energies. Consequently, beyond the range of the backscattered electrons, the dose upstream is unaffected by the presence of the interface. A similar dose enhancement has been reported for kilovoltage beams. In this case, due to the very low energy of the backscattered electrons, the enhancement persists for a very short upstream distance. Since photon interaction cross sections at keV energies are relatively large, there is also a substantial backscattered photon fluence. This experimental work investigates the effect of these photons on dose at distances upstream from a water/lead interface beyond the range of the backscattered electrons. Measurements of ionization charge, as a function of interface distance and field size for 60, 100, and 250 kV beams, were made with a parallel plate chamber at a fixed depth. A significant underdose was found upstream of the interface compared to a homogeneous water medium. For example, with the 100 kV beam and a 15 x 15 cm2 field the measured underdose is 23% at 3 mm and 14% at 1.5 cm upstream of the interface. The effect decreases with field size. In fact, for a 2 x 2 cm2 field the upstream dose in unaffected by the interface. Detailed results for this and the other two beams are presented along with backscatter factor measurements for lead. An explanation for the observed underdose is also presented. PMID- 1512155 TI - Portal radiography practice in Canada. PMID- 1512156 TI - Can lung cancer be cured by irradiation alone? PMID- 1512157 TI - Radiation tolerance and the new biology: growth factor involvement in radiation injury to the lung. PMID- 1512158 TI - Prophylactic cranial irradiation for lung cancer patients. PMID- 1512159 TI - Re: Editorial by Dr. Deutsch. PMID- 1512160 TI - Combined modality treatment for locally recurrent rectal cancer. PMID- 1512161 TI - Observations on the predictive value of perfusion lung scans on post-irradiation pulmonary function among 210 patients with bronchogenic carcinoma. AB - As a component of treatment planning for thoracic irradiation (RT), 210 bronchogenic carcinoma patients seen at the Fox Chase Cancer Center from 1983 to 1990 underwent quantitative perfusion scans, superimposition of their RT treatment fields onto these scans, and pulmonary function testing. These studies were used to prospectively estimate the influence of the planned thoracic irradiation on pulmonary function, as measured by the forced expiratory volume in one second (FEV1). Among the 156 patients with unresected lesions, the mean pre RT FEV1 was 1.71 +/- 0.67 liters (+/- standard deviation), and the mean percentage of total lung perfusion within the treatment field was 31.0 +/- 12.1%. Mean values for the 54 patients treated post-operatively were 1.79 liters (pre-RT FEV1) and 28.8% (% perfusion within RT field). Using this technique, the prospectively predicted post-RT FEV1 is the product of the pre-RT FEV1 (1% of total lung perfusion within the treatment field). The mean predicted post treatment FEV1 for the nonoperative patients was 1.15 +/- 0.43 liters and 1.25 +/ 0.41 liters for the postoperative patients. Forty-three nonoperative and 19 postoperative patients had FEV1 determinations following RT, at a mean post-RT interval of 11 months for nonoperative patients and 23 months for post-operative patients. Among nonoperative patients, 53% had no change in post-RT FEV1, 19% improved, while 22% had readings declining toward the predicted value. Only 5% had readings below predicted. Among postoperative patients, 37% had no change or improvement, 37% declined toward the predicted, 10% declined to predicted, and 11% had values worse than predicted. This technique of superimposing RT fields onto lung perfusion scans predicts for a degree of pulmonary impairment which is observed in only a minority of patients (10%) and which is rarely exceeded (6%). PMID- 1512163 TI - Supratentorial malignant glioma: patterns of recurrence and implications for external beam local treatment. AB - Pre- and postoperative computerized tomography scans, simulator films, and computerized tomography scans documenting tumor recurrence were analyzed on 70 patients with supratentorial malignant glioma treated with whole brain plus boost radiation therapy to determine sites of recurrence in relation to the boost. The boost was planned using the postoperative computerized tomography scan. Tumor recurred in 53 patients--within the boost in 38 (72%), partly outside the boost in 12 (23%), outside the boost but within the brain in one (2%), in the boost and in the spinal cord in one (2%), and in the spinal cord only in one (2%). All recurrences confined to the brain were found within 4 cm of the enhancing tumor as defined by the preoperative computerized tomography scan. Recurrences outside the boost were more common with inadequate boost margins, small boost volumes, temporal lobe tumors, and homolateral wedge pair technique. Survival was not adversely affected by recurrence outside the boost. We recommend that patients with malignant glioma be treated by parallel opposed fields with a margin that is 4 cm beyond the edge of the preoperative enhancing tumor, as seen on computerized tomography scan. PMID- 1512162 TI - Long-term neuropsychologic sequelae of childhood leukemia: comparison of two CNS prophylactic regimens. AB - To compare the late neuropsychologic toxicities of CNS prophylaxis in childhood acute lymphoblastic leukemia (ALL), a transversal assessment was performed in two groups of ALL patients and two control groups. The ALL patients had received one of the following CNS prophylaxes: cranial irradiation, 24 Gy and i.t. MTX 10 mg/m2, 6 doses (RT group, n = 25) or i.t. Ara-C 30 mg/m2 and i.t. MTX 10 mg/m2, 10 doses (ChT group, n = 29). The two control groups were: Siblings (Sb, n = 24) and Solid Tumors (ST, n = 22). Intelligence Quotient (IQ), memory, learning, attention and frontal tasks were studied. Comparative analyses between ChT and RT showed no differences in any of the tests. When RT was compared with ST or Sb, RT showed a 10-point lower mean IQ (p greater than 0.05). The results of ChT versus ST or versus Sb were worse in the ChT group. In many tests the differences were statistically significant. Analyses of the 54 ALL patients compared with the 46 controls showed significant differences in all tests except verbal memory and verbal learning. Neuropsychological sequelae of CNS prophylaxis are discussed, and in particular, the role of cranial radiotherapy and i.t. Ara-C. We conclude that prophylactic CNS therapy may cause cognitive dysfunctions. PMID- 1512164 TI - Second head and neck cancers following radiation therapy of T1 and T2 cancers of the oral cavity and oropharynx. AB - The risk of second cancer in the head and neck region following definitive radiation therapy was evaluated among 600 patients who were treated for T1 and T2 cancers of the oral cavity and oropharynx at the Henri Mondor hospital between January 1970 and March 1987. Seventy-five patients (12.5%) were managed with external irradiation only, 243 (40.5%) with RT and Iridium 192, and 282 (47%) with Iridium 192 alone. One hundred fifteen patients (19%) developed a second cancer from 3 to 183 months after initial therapy (median: 32 months), including 69 patients (11.5%) in whom the second malignancy was diagnosed in the head and neck region. An increased and constant actuarial risk of development of second head and neck cancer was found (2.7%/year of observation). Univariate analysis showed that age, sex, stage, and modality of the initial treatment did not influence the risk of second head and neck cancer; there was a greater risk of second head and neck malignancy for those patients with soft palate carcinoma (p less than 0.05). Multivariate analysis revealed that the only group of patients who developed a second head and neck cancer more frequently were those who were irradiated with Iridium 192 only (p = 0.0076). There was a trend toward a greater risk of second head and neck malignancy for those with soft palate carcinoma (p = 0.059). Radical treatment of the second head and neck malignancy by surgery and/or re-irradiation was performed for 67% of patients. Patients initially treated by Iridium 192 only could undergo salvage treatment more often than those who previously received external beam radiotherapy (79% vs 53%, p = 0.02). The overall 2-year and 5-year survivals after the diagnosis of the second head and neck cancer were 32% and 10%, respectively. PMID- 1512165 TI - Seventeen years experience with accelerated radiotherapy for carcinoma of the breast. AB - Between 1973 and 1989, one hundred and three women received accelerated radiotherapy to the breast. Fifteen of them had the treatment after local tumor removal; the rest had primary radiotherapy for inoperable cancer. Eleven patients were irradiated twice a day, 83 three times a day, and nine four times a day. The overall time was five days in 52 courses, 7-15 days in 49 courses, and two patients had a longer regime. Actuarial local tumor control was 34.6% at five, and 24.7% at ten years in the whole group, and 25.5% and 14.6%, respectively, in the patients with macroscopical disease. Crude local control in the latter patients was achieved in 24.4% after a five day course, 28.8% after 7 to 11 days course, and 50% after a time of 12 or more days. Crude local control after total dose of less than 40 Gy was 15.8%, after 40-45 Gy, 31.7%, after 45.1-50 Gy, 33.3%, and after more than 50 Gy, 100% (four patients). Sixty patients were evaluable for late damage at 18 months; twenty three of them developed moderate changes. Six suffered severe late damage such as skin leathering or necrosis: three of them were treated for recurrence after previous radiotherapy. The main factor influencing tumor control was not the overall treatment time, but the total dose. PMID- 1512166 TI - M4 protocol for cerebellar medulloblastoma: supratentorial radiotherapy may not be avoided. AB - The main goal of the M4 protocol was to evaluate the efficacy of treatment excluding supratentorial radiation in patients with newly diagnosed medulloblastoma. All patients underwent surgical resection and received postoperative chemotherapy. Chemotherapy was adapted to the initial staging and prognostic factors (Group A: good-risk; Group B: poor-risk). Chemotherapy was started early after surgery, and consisted of two courses of the "eight drug in one day" regimen and two courses of high dose methotrexate. Radiotherapy was delayed until 5 (Group B) to 7 (Group A) weeks after the first course of chemotherapy. Radiotherapy was administered only to the posterior fossa and the spinal axis. Only 3/16 patients (18%) are alive and disease-free with a mean follow up of 6 years. The site of progression was supratentorial in 9 out of 13 patients and three patients had spinal and/or cerebrospinal fluid relapses. Only one patient had isolated posterior fossa relapse. The mean time to relapse was 484 days. We conclude that the chemotherapy regimens used in the M4 protocol do not allow the reduction of irradiation fields in patients with cerebellar medulloblastoma. In spite of long-term side effects on neurocognitive functions, supratentorial radiotherapy should remain a major component of medulloblastoma treatment. PMID- 1512167 TI - Tumor cell kinetics, local tumor control, and accelerated radiotherapy: a preliminary report. AB - The local tumor control achieved in patients treated in a pilot study of continuous, hyperfractionated, accelerated radiotherapy has been related to the tumor cell kinetics evaluated by in vivo administration of bromodeoxyuridine and flow cytometry. In 42 of 50 patients with advanced squamous cell carcinomas in the head and neck region it was possible to sample the primary tumor prior to treatment. In three further cases, involved regional nodes were studied: in the remaining five, tissue was obtained subsequently either from a local recurrence or from a distant metastasis. Successful cell kinetic measurements were made in 38 (90%) of the 42 primary tumors. The median values of the labelling index, the duration of the DNA synthetic phase and, thus, the potential doubling time for all primaries were 7.1%, 9.8 hr, and 3.9 days, respectively. Complete regression was achieved in 28 (74%) of the primary tumors and in 23 (61%) this was maintained to the time of observation for this report. There was no significant influence of any of the cell kinetic parameters upon the immediate or longer term local tumor control. This result is compatible with the overcoming of cellular repopulation by the acceleration of radiotherapy. PMID- 1512168 TI - Molecular biology mechanisms in the radiation induction of pulmonary injury syndromes: interrelationship between the alveolar macrophage and the septal fibroblast. AB - Pulmonary fibrosis is a crippling, essentially lethal chronic disease due to an interplay of events following irradiation between the pneumonitic and fibrotic phases. In this series of experiments it is demonstrated that there is no latent period after irradiation, but an immediate intercellular communication system which springs into action to initiate recovery. Latency was only a function of our inability to uncover the molecular events that precede and underlie the clinical pathologic course of organ/tissue irradiation. Current advances in understanding the production of growth factors by different cells provides new insights to autocrine, paracrine and endocrine messages as a basis for understanding radiation pathophysiology as a progressive process that is amplified by other injurious events such as chemotoxicity. This is the first demonstrated release of trophic factors (cytokines) after in vivo irradiation that persists up to a month after exposure, suggesting that the persistence of a small incremental stimulus during a silent "latent" period can be the basis for the clinical pathologic expression of a late radiation effect, that is, pulmonary interstitial fibrosis. PMID- 1512169 TI - Jung's infancy and childhood and its influence upon the development of analytical psychology. PMID- 1512170 TI - Dreams of anorexic and bulimic women. A research study. AB - The research paradigms used in this study fit with the content analysis paradigms of Hall and Van de Castle (1966) and Dippel et al. (1987), but differ in the use of descriptive scenarios specific to eating disorders. Anorexic and bulimic patients are often able to share their dreams with their therapists, and this process is sometimes the start of building an analytical relationship. This study compared the dreams of twelve eating-disordered women with eleven 'normal' women. A total of 275 dreams was collected over a four-week period and rated on a 91 item scale (Brink 1991) by eight raters. Significant differences were found between the two groups, with eating-disordered women having more dream scenarios depicting themes of: impending doom at the end of the dream, attitudes of 'whatever I do I won't succeed', and images of the dreamer being attacked, and being watched. Significant differences were also found in dream content portraying the psychological traits of: ineffectiveness, self-hate, negative emotions, an inability to self-nourish, obsession with weight, and anger. The discussion centres around the role of 'inordinate oral rage', the nature of ego defences, how these defences manifest themselves in dream images and in daily living, and how they severely impair positive transformative processes. The implications for clinical practice are that dreams are an amenable way of working with eating-disordered women, and that the therapist is more likely to promote positive transformation through focusing on their dreams than trying to change their behaviour. PMID- 1512172 TI - Marie-Jose Dicks-Mireaux (1928-1992). PMID- 1512171 TI - Soul on ice; soul on fire. Abandonment, impingement, and the space between. PMID- 1512173 TI - The microbiological hazards of municipal and clinical wastes. PMID- 1512175 TI - An investigation of the antibacterial effect of carrot on Listeria monocytogenes. AB - Carrot slices immersed in a potassium phosphate buffer (0.1 mol/l, pH 7.0) or carrot tissue macerated in the buffer had a lethal effect on Listeria monocytogenes. This antilisterial activity was suppressed by anaerobiosis, thiol compounds (1 mmol/l) and bovine serum albumin (0.05%) but was not affected by sodium ascorbate (200 mmol/l), propyl gallate (25 mmol/l), catalase (1100 U/ml), superoxide dismutase (357 U/ml), or chelating agents (10 mmol/l). Free-radical scavengers had no effect at 10 mmol or 50 mmol/l but histidine and diazabenzocyclooctane at 100 mmol/l reduced the antilisterial activity. The addition of Tween 20, 0.05% (v/v), to carrot macerates improved the recovery of the activity in the supernatant liquid after centrifugation at 10,000 g for 2 min. The addition of higher concentrations of the detergent to the macerate reduced the antilisterial activity. PMID- 1512174 TI - Co-existence of beta-lactamase and penicillin acylase in bacteria; detection and quantitative determination of enzyme activities. AB - Twenty-six bacteria were examined for the presence of penicillin acylase and beta lactamase. A copper reducing assay, which was sensitive in the analytical range 2 20 micrograms/ml, was used for determination of penicilloates and a fluorescamine assay was used to determine 6-aminopenicillanic acid concentrations when both substances were produced by the action of the enzymes on a single substrate. Seventeen bacteria contained beta-lactamases, six contained penicillin acylases and four contained both enzymes. Two bacteria contained a Type 1 penicillin acylase and four bacteria contained a Type II enzyme. No ampicillin acylases were detected. All beta-lactamases were constitutive enzymes in those organisms where both enzymes co-existed. Bacillus subtilis and B. cereus produced inducible and extracellular beta-lactamases. Acinetobacter calcoaceticus ATCC 21288 produced a constitutive beta-lactamase which was detected extracellularly. PMID- 1512176 TI - Survival of bacterial enteric pathogens in traditional fermented foods. AB - The survival of strains of bacterial enteric pathogens was investigated in two traditional fermented foods (mahewu and sour porridge) and in unfermented porridge. The foods were inoculated with cell suspensions of Salmonella, Shigella, Campylobacter, Aeromonas species and pathogenic Escherichia coli which had a final concentration of 10(6)-10(7) cfu/ml of food. None of the strains of Aeromonas and Campylobacter were detected in mahewu and sour porridge 20 min after inoculation. The salmonellas were not found 4 h after inoculation in either fermented foods but the shigellas and pathogenic E. coli strains were more tolerant to the low pH of the fermented foods. Some of the shigellas and pathogenic E. coli strains survived for 24 h after inoculation but showed a sharp decrease in numbers. All the strains of the enteric pathogens survived for 24 h in the unfermented porridge and increased in the numbers except for campylobacters, the numbers of which declined. These results suggest that the traditional fermented foods have bacteriostatic and bactericidal properties and are unlikely to play a major role in the transmission of bacterial enteric pathogens. PMID- 1512177 TI - The use of immobilized lectins in the separation of Staphylococcus aureus, Escherichia coli, Listeria and Salmonella spp. from pure cultures and foods. AB - Lectins from Helix pomatia, Canavalia ensiformis, Agaricus bisporus and Triticum vulgaris agglutinated cultures of Staphylococcus aureus, Escherichia coli, Listeria and Salmonella spp. This agglutination was specific as it was inhibited (except with A. bisporus lectin) by the competing sugar substrates. The ability of three of these lectins, immobilized on a variety of supports, to separate these micro-organisms from pure cultures was investigated. Immobilization of the lectins on magnetic microspheres was the most effective method. Immobilized T. vulgaris lectin bound 87-100% of cells from cultures of L. monocytogenes, 80-100% of Staph. aureus, 33-45% of Salmonella spp. and 42-77% of E. coli. The A. bisporus lectin bound 31-63% of cells in cultures of L. monocytogenes, 83% of Staph. aureus but only 3-5% of the salmonella cells. Similarly H. pomatia lectin bound greater than 92% of Staph. aureus and 64% of L. monocytogenes cells but was poor at binding the Gram-negative organisms. This preference for binding Gram positive organisms was confirmed when mixed cultures were studied. The T. vulgaris lectin was effective in removing L. monocytogenes (43%) and Staph. aureus (26%) from diluted milk and Salmonella (31-54%) from raw egg. Agaricus bisporus lectin removed L. monocytogenes from undiluted milk (10-47%) or ground beef (32-50%). PMID- 1512178 TI - A combined PCR and selective enrichment method for rapid detection of Listeria monocytogenes. AB - Development of a routine detection assay for Listeria monocytogenes in foods that uses the polymerase chain reaction (PCR) and enrichment cultures was investigated. Oligonucleotide primers were chosen to amplify a 3' region of L. monocytogenes hlyA gene spanning a conserved HindIII site. PCR detection sensitivity for L. monocytogenes in dilutions of pure enrichment cultures was between 50 and 500 colony forming units. A short enrichment period before PCR amplification allowed detection of the organisms in a range of complex foods contaminated with 10(4) cfu/g. Detection sensitivity for the assay in the presence of chicken skin and soft cheese was determined at 10-100 cfu/g. Utilization of enrichment cultures and PCR allowed identification of the organism within 24 h or 2 days. PMID- 1512179 TI - A note on the use of a plasmid as a DNA probe in the detection of a Lactobacillus fermentum strain in porcine stomach contents. AB - A plasmid (about 50 kb) was used as a DNA probe to enumerate, by colony hybridization, a strain of Lactobacillus fermentum in the stomach contents of eight piglets. The population sizes obtained by colony hybridization were in agreement with estimated levels calculated on the basis of plasmid profiling of colonies isolated at random from the total lactobacillus population. PMID- 1512180 TI - Effectiveness of handwashing agents in eliminating Staphylococcus aureus from gloved hands. AB - The recent emphasis on gloving has resulted in accounts of healthcare workers washing gloves instead of changing them. This study evaluated the efficacy of soap and three germicidal agents in decontaminating latex and vinyl medical gloves that were experimentally contaminated with Staphylococcus aureus. Gloves were tested for perforations before and after the glove-washing procedure. Results of this study demonstrated that contamination was reduced from the glove surfaces. Although the routine washing of gloved hands cannot be recommended, it may be carried out under limited circumstances. PMID- 1512181 TI - Evaluation of the repeatability and reproducibility of European suspension test methods for antimicrobial activity of disinfectants and antiseptics. AB - A collaborative study to determine the precision of the 1987 Method of test for the antimicrobial activity of disinfectants in food hygiene is described. The repeatability and reproducibility of the test was found to vary according to the nature of the test organism, the type of disinfectant product and the skill of the operator. Results indicate that significant differences in microbicidal effect (ME values) occur within test laboratories between test periods as well as between laboratories, and that much of this variability derives from apparently random variations in the resistance of test strains from day to day and test period to test period. Indications are that although the test is sufficiently reliable to be used as a standard method, adequate test replication must be specified to distinguish borderline pass from borderline fail disinfectant concentrations. The implications of the results in relation to current work on the development of unified European test methods for disinfectants is discussed. PMID- 1512182 TI - A multiple logistic model for predicting the occurrence of Campylobacter jejuni and Campylobacter coli in water. AB - A multiple logistic regression model was established to predict the occurrence of Campylobacter jejuni/coli, related to index bacteria such as faecal coliforms, faecal streptococci, and sulphite-reducing clostridia, in a water source in southern Norway. The fitted model indicated that faecal coliforms were strong predictors for C. jejuni/coli, although the water temperature also had a strong influence on results. Sulphite-reducing clostridia, faecal streptococci, and season of the year had no significant influence on the results, in spite of their apparent predictor value as separate variables. The model employed offers a new approach to the relationship between index bacteria and the occurrence of pathogenic bacteria in water. Similar models can also be established in general food microbiology. PMID- 1512183 TI - Self- and supervisory perspectives on age and work attitudes and performance. AB - Person- and context-oriented definitions of age were used to predict three sets of work outcomes: work attitudes, performance ratings, and reports of developmental practices. The five age measures included employee chronological age, employee subjective age (i.e., self-perceptions of age), and social age (i.e., others' perceptions of age), as well as self- and supervisors' perceptions of the employee's relative age (i.e., compared with the employee's work group). The study assessed (a) the relationships among the age measures, (b) the additive relationships among the age measures that predicted work outcomes, and (c) the interactive relationships among the age measures that predicted work outcomes. Each prediction received some support except for (b). Furthermore, many of the age--work-outcome relationships were replicated in the managerial sample. Implications for the use of alternative age measures are discussed. PMID- 1512184 TI - Frame-of-reference training and cognitive categorization: an empirical investigation of rater memory issues. AB - We considered the effects of frame-of-reference (FOR) training on raters' ability to correctly classify ratee performance as well as their ability to recognize previously observed behaviors. The purpose was to examine the cognitive changes associated with FOR training to better understand why such training generally improves rating accuracy. We trained college students (N = 94) using either FOR or control procedures, had them observe three managers on videotape, and rate the managers on three performance dimensions. Results supported our hypotheses that, compared with control training, FOR training led to better rating accuracy and better classification accuracy. Also consistent with predictions, FOR training resulted in lower decision criteria (i.e., higher bias) and lower behavioral accuracy on a recognition memory task involving impression-consistent behaviors. The implications of these results are discussed, particularly in terms of the ability of FOR-trained raters to provide accurate performance feedback to ratees. PMID- 1512185 TI - Effects of alcohol intoxication on risk taking, strategy, and error rate in visuomotor performance. AB - Adult men (N = 44) participated for 2 days (alcohol vs. placebo treatment) in a double-blind, crossover experiment. Performance on the Digit Symbol Substitution Task (DSST) and a visuomotor (VM) task was measured 4 times each day. On the alcohol-treatment day, data were obtained once during ascending breath alcohol levels (BALs), once during maximal BALs (0.05 or 0.10), and twice during descending BALs. Data were collected at the same time points on the placebo treatment day. Limited evidence for acute tolerance was obtained with the DSST, but error rates on the VM task were higher during maximal and descending BALs. Error rates remained near placebo values, and participants displayed slightly greater caution, while BALs were ascending. Strategy scores on the VM task exceeded placebo scores during maximal intoxication. Data interpretation is focused on individuals in higher level (e.g., professional) positions. PMID- 1512186 TI - Methane from acetate. AB - The general features are known for the pathway by which most methane is produced in nature. All acetate-utilizing methanogenic microorganisms contain CODH which catalyzes the cleavage of acetyl-CoA; however, the pathway differs from all other acetate-utilizing anaerobes in that the methyl group is reduced to methane with electrons derived from oxidation of the carbonyl group of acetyl-CoA to CO2. The current understanding of the methanogenic fermentation of acetate provides impressions of nature's novel solutions to problems of methyl transfer, electron transport, and energy conservation. The pathway is now at a level of understanding that will permit productive investigations of these and other interesting questions in the near future. PMID- 1512187 TI - A combined genetic and physical map of the Streptomyces coelicolor A3(2) chromosome. AB - The restriction enzymes AseI (ATTAAT), DraI (TTTAAA), and SspI (AATATT) cut the Streptomyces coelicolor A3(2) chromosome into 17, 8, and 25 fragments separable by pulsed-field gel electrophoresis (PFGE). The sums of their lengths indicated that the chromosome consists of about 8 Mb of DNA, some 75% more than that of Escherichia coli K-12. A physical map of the chromosome was constructed for AseI and DraI, using single and double digests, linking clones, cross-hybridization of restriction fragments, and locations of genetically mapped genes, insertion sequences, prophages, and the integrated SCP1 and SLP1 plasmids on the physical map. The physical map was aligned with the previously established genetic map, revealing that the two long opposite quadrants of the genetic map that are almost devoid of markers (the silent regions at 3 o'clock and 9 o'clock) are indeed physically long rather than being hot spots for genetic exchange. They must therefore contain long stretches of DNA different in function from the remainder of the genome. Consistent with this conclusion are the locations of significant deletions in both of the silent regions. Of these, a 40-kb deletion in the 9 o'clock region accompanied or followed integration of the SCP1 linear plasmid to produce the NF fertility state. PFGE analysis of Streptomyces lividans 66, a close relative of S. coelicolor A3(2), was hampered by the previously described susceptibility of its DNA to degradation during electrophoresis. However, ZX7, a mutant derivative of S. lividans lacking the DNA modification responsible for this degradation, yielded good PFGE preparations. Not more than 7 of the 17 S. coelicolor AseI fragments could be shared by the S. lividans strain. PMID- 1512188 TI - GCR3 encodes an acidic protein that is required for expression of glycolytic genes in Saccharomyces cerevisiae. AB - Screening of a mutagenized strain carrying a multicopy ENO1-'lacZ fusion plasmid revealed a new mutation affecting several glycolytic enzyme activities. The recessive single nuclear gene mutation, named gcr3, caused an extremely defective growth phenotype on fermentable carbon sources such as glucose, while growth on respiratory media was almost normal. The GCR3 gene was obtained by growth complementation from a genomic DNA library, and the complemented strains had normal enzyme levels. GCR3 gene was sequenced, and a 99,537-Da protein was predicted. The predicted GCR3 protein was fairly acidic (net charge, -34). The C terminal region was highly charged, and an acidic stretch was found in it. PMID- 1512189 TI - Anaerobic fumarate transport in Escherichia coli by an fnr-dependent dicarboxylate uptake system which is different from the aerobic dicarboxylate uptake system. AB - Escherichia coli grown anaerobically with fumarate as electron acceptor is able to take up C4-dicarboxylates by a specific transport system. The system differs in all tested parameters from the known aerobic C4-dicarboxylate transporter. The anaerobic transport system shows higher transport rates (95 mumol/g [dry weight] per min versus 30 mumol/g/min) and higher Kms (400 versus 30 microM) for fumarate than for the aerobic system. Mutants lacking the aerobic dicarboxylate uptake system are able to grow anaerobically at the expense of fumarate respiration and transport dicarboxylates with wild-type rates after anaerobic but not after aerobic growth. Transport by the anaerobic system is stimulated by preloading the bacteria with dicarboxylates. The anaerobic transport system catalyzes homologous and heterologous antiport of dicarboxylates, whereas the aerobic system operates only in the unidirectional mode. The anaerobic antiport is measurable only in anaerobically grown bacteria with fnr+ backgrounds. Additionally, the system is inhibited by incubation of resting bacteria with physiological electron acceptors such as O2, nitrate, dimethyl sulfoxide, and fumarate. The inhibition is reversed by the presence of reducing agents. It is suggested that the physiological role of the system is a fumarate/succinate antiport under conditions of fumarate respiration. PMID- 1512190 TI - Effect of D-amino acids on structure and synthesis of peptidoglycan in Escherichia coli. AB - Growth of Escherichia coli in the presence of certain D-amino acids, such as D methionine, results in the incorporation of the D-amino acid into macromolecular peptidoglycan and can be lethal at high concentrations. Previous studies suggested that incorporation was independent of the normal biosynthetic pathway. An enzymatic reaction between the D-amino acid and macromolecular peptidoglycan was proposed as the mechanism of incorporation. The application of more advanced analytical techniques, notably high-pressure liquid chromatography, revealed that the presence of a D-amino acid susceptible to incorporation induced a multiplicity of alterations in peptidoglycan metabolism. Results derived basically from the study of samples treated with D-Met, D-Trp, and D-Phe indicated that the incorporation of a D-amino acid results in the accumulation of two major new muropeptides whose general structures most likely are GlucNAc MurNAc-L-Ala-D-Glu-m-diaminopimelic acid-D-aa and GlucNAc-MurNAc-L-Ala-D-Glu-m diaminopimelic acid-D-Ala-GlucNAc-MurNAc-L-Ala-D-Glu-m-diaminopimelic acid-D-aa, where D-aa represents a residue of the added D-amino acid. Resting cells are proficient in the incorporation of D-amino acids and can reach peptidoglycan modification levels comparable to those in growing cells. Under our conditions, D amino acids had no apparent effect on growth or morphology but caused a severe inhibition of peptidoglycan synthesis and cross-linking, possibly leading to a reduction in the amount of peptidoglycan per cell. The properties of the reaction support the involvement of a penicillin-insensitive LD-transpeptidase enzyme in the synthesis of modified muropeptides and a possible inhibitory action of D amino acids on high-molecular-weight penicillin-binding proteins. PMID- 1512191 TI - Properties of subcloned subunits of bacterial acetohydroxy acid synthases. AB - The acetohydroxy acid synthase (AHAS) isozymes from enterobacteria are each composed of a large and small subunit in an alpha 2 beta 2 structure. It has been generally accepted that the large (ca. 60-kDa) subunits are catalytic, while the small ones are regulatory. In order to further characterize the roles of the subunits as well as the nature and the specificities of their interactions, we have constructed plasmids encoding the large or small subunits of isozymes AHAS I and AHAS III, each with limited remnants of the other peptide. The catalytic properties of the large subunits have been characterized and compared with those of extracts containing the intact enzyme or of purified enzymes. Antisera to the isolated subunits have been used in Western blot (immunoblot) analyses for qualitative and semiquantitative determinations of the presence of the polypeptides in extracts. The large subunits of AHAS isozymes I and III have lower activities than the intact enzymes: Vmax/Km is 20 to 50 times lower in both cases. However, for AHAS I, most of this difference is due to the raised Km of the large subunit alone, while for AHAS III, it is due to a lowered Vmax. The substrate specificities, R, of large subunits are close to those of the intact enzymes. The catalytic activity of the large subunits of AHAS I is dependent on flavin adenine dinucleotide (FAD), as is that of the intact enzyme, although the apparent affinities of the large subunits alone for FAD are 10-fold lower. Isolated subunits are insensitive to valine inhibition. Nearly all of the properties of the intact AHAS isozyme I or III can be reconstituted by mixing extracts containing the respective large and small subunits. The mixing of subunits from different enzymes does not lead to activation of the large subunits. It is concluded that the catalytic machinery of these AHAS isozymes is entirely contained within the large subunits. The small subunits are required, however, for specific stabilization of an active conformation of the large subunits as well as for value sensitivity. PMID- 1512192 TI - Site-specific integration of the temperate bacteriophage phi adh into the Lactobacillus gasseri chromosome and molecular characterization of the phage (attP) and bacterial (attB) attachment sites. AB - The temperate bacteriophage phi adh integrates its genome into the chromosomal DNA of Lactobacillus gasseri ADH by a site-specific recombination process. Southern hybridization analysis of BclI-digested genomic DNA from six relysogenized derivatives of the prophage-cured strain NCK102 displayed phage chromosomal junction fragments identical to those of the lysogenic parent. The phi adh attachment site sequence, attP, was located within a 365-bp EcoRI-HindIII fragment of phage phi adh. This fragment was cloned and sequenced. DNA sequence analysis revealed striking features common to the attachment sites of other site specific recombination systems: five direct repeats of the sequence TGTCCCTTTT(C/T) and a 14-bp inverted repeat. Oligonucleotides derived from the sequence of the attP-containing fragment enabled us to amplify predicted junction fragment sequences and thus to identify attL, attR, and attB. The core region was defined as the 16-bp sequence TACACTTCTTAGGAGG. Phage-encoded functions essential for site-specific insertion of phage phi adh were located in a 4.5-kb BclI fragment. This fragment was cloned in plasmid pSA34 to generate the insertional vector pTRK182. Plasmid pTRK182 was introduced into L. gasseri NCK102 by electroporation. Hybridization analysis showed that a single copy of pTRK182 had integrated at the attB site of the NCK102 erythromycin-resistant transformants. This is the first site-specific recombination system described in lactobacilli, as well as the first attP-based site-specific integration vector constructed for L. gasseri ADH. PMID- 1512193 TI - Efficiency of homologous intermolecular recombination at different locations on the Bacillus subtilis chromosome. AB - The efficiencies of intermolecular recombination at 12 different locations on the Bacillus subtilis chromosome were determined by transforming competent cells with a nonreplicative plasmid. The efficiencies varied by only about threefold but were significantly different (P less than 0.05 by a chi-square test) for approximately 20% of the locations. The recA gene product is required for recombination, and the addA gene product appears to affect the variation in a site-specific way. PMID- 1512194 TI - Mini-F plasmid mutants able to replicate in Escherichia coli deficient in the DnaJ heat shock protein. AB - A subset of Escherichia coli heat shock proteins, DnaJ, DnaK, and GrpE, is required for mini-F plasmid replication, presumably at the step of functioning of the RepE initiator protein. We have isolated and characterized mini-F plasmid mutants that acquired the ability to replicate in the Escherichia coli dnaJ259. The mutant plasmids were found to replicate in any of dnaJ, dnaK, and grpE mutant hosts tested. In each case, the majority of the mutant plasmids carried a unique amino acid alteration in a localized region of repE coding sequence and showed an increased copy number, whereas the minority contained a common single base change (C to T) in the promoter/operator region and produced an increased amount of RepE. All RepE proteins with altered residues (between 92 and 134) exhibited increased initiator activities (hyperactive), and many showed reduced repressor activities as well, indicating that this region is important for the both major functions of RepE protein. These results together with evidence reported elsewhere indicate that the subset of heat shock proteins serves to activate RepE protein prior to or during its binding to the replication origin and that the mutant RepE proteins are active even in their absence. We also found that a C terminal lesion (repE602) reduces the initiator activity particularly of some hyperactive mutant RepE proteins but does not affect the repressor activity. This finding suggests a functional interaction between the central and C-terminal regions of RepE in carrying out the initiator function. PMID- 1512195 TI - Cloning, characterization, and DNA base sequence of the high-level streptomycin resistance gene strA1 of Haemophilus influenzae Rd. AB - The high-level streptomycin resistance strA1 gene of Haemophilus influenzae Rd was cloned in plasmid pAT4 as a 2.1-kbp EcoRI insert. It was later replaced in pAT4 by the wild-type strA+ gene. Plasmid pAT4 carrying the strA+ gene is highly unstable and renders chromosomally resistant recipients sensitive to streptomycin. The strA+ gene and the instability factor both reside on a 500-base HindIII-EcoRI subfragment. The two biological activities are also expressed in Escherichia coli. Both wild-type (strA+) and mutant (strA1) genes were sequenced. They show considerable nucleotide homology with the E. coli strA+ gene and its product. PMID- 1512196 TI - Location and characterization of genes involved in binding of starch to the surface of Bacteroides thetaiotaomicron. AB - Previous studies of starch utilization by the gram-negative anaerobe Bacteroides thetaiotaomicron have demonstrated that the starch-degrading enzymes are cell associated rather than extracellular, indicating that the first step in starch utilization is binding of the polysaccharide to the bacterial surface. Five transposon-generated mutants of B. thetaiotaomicron which were defective in starch binding (Ms-1 through Ms-5) had been isolated, but initial attempts to identify membrane proteins missing in these mutants were not successful. We report here the use of an immunological approach to identify four maltose inducible membrane proteins, which were missing in one or more of the starch binding mutants of B. thetaiotaomicron. Three of the maltose-inducible proteins were outer membrane proteins (115, 65, and 43 kDa), and one was a cytoplasmic membrane protein (80 kDa). The genes encoding these proteins were shown to be clustered in an 8.5-kbp segment of the B. thetaiotaomicron chromosome. Two other loci defined by transposon insertions, which appeared to contain regulatory genes, were located within 7 kbp of the cluster of membrane protein genes. The 115-kDa outer membrane protein was essential for utilization of maltoheptaose (G7), whereas loss of the other proteins affected growth on starch but not on G7. Not all of the proteins missing in the mutants were maltose regulated. We also detected two constitutively produced proteins (32 and 50 kDa) that were less prominent in all of the mutants than in the wild type. Both of these were outer membrane proteins. PMID- 1512198 TI - Enhanced export of beta-galactosidase fusion proteins in prlF mutants is Lon dependent. AB - We have used fusions of the outer membrane protein LamB to beta-galactosidase (encoded by lacZ) to study the protein export process. This LamB-LacZ hybrid protein blocks export when synthesized at high levels, as evidenced by inducer (maltose) sensitivity, a phenomenon termed LacZ hybrid jamming. The prlF1 mutation relieves LacZ hybrid jamming and allows localization of the fusion protein to a noncytoplasmic compartment. prlF1 and similar alleles are gain-of function mutations. Null mutations in this gene confer no obvious phenotypes. Extragenic suppressors of a gain-of-function prlF allele have been isolated in order to understand how this gene product affects the export process. The suppressors are all lon null mutations, and they are epistatic to all prlF phenotypes tested. Lon protease activity has been measured in prlF1 cells and shown to be increased. However, the synthesis of Lon is not increased in a prlF1 background, suggesting a previously unidentified mechanism of Lon activation. Further analysis reveals that prlF1 activates degradation of cytoplasmically localized precursors in a Lon protease-dependent manner. It is proposed that accumulation of precursors during conditions of hybrid protein jamming titrates an essential export component(s), possibly a chaperone. Increased Lon-dependent precursor degradation would free this component, thus allowing increased protein export under jamming conditions. PMID- 1512197 TI - Purification and phosphorylation of the Arc regulatory components of Escherichia coli. AB - In Escherichia coli, a two-component signal transduction system, consisting of the transmembrane sensor protein ArcB and its cognate cytoplasmic regulatory protein ArcA, controls the expression of genes encoding enzymes involved in aerobic respiration. ArcB belongs to a subclass of sensors that have not only a conserved histidine-containing transmitter domain but also a conserved aspartate containing receiver domain of the regulator family. 'ArcB (a genetically truncated ArcB missing the two transmembrane segments on the N-terminal end) and ArcA were purified from overproducing cells. Autophosphorylation of 'ArcB was revealed when the protein was incubated with [gamma-32P]ATP but not with [alpha 32P]ATP or [gamma-32P]GTP. When ArcA was incubated in the presence of 'ArcB and [gamma-32P]ATP, ArcA acquired radioactivity at the expense of the phosphorylated protein 'ArcB-32P. When a limited amount of 'ArcB was incubated with excess ArcA and [gamma-32P]ATP, ArcA-32P increased linearly with time. Under such conditions, for a given time period the amount of ArcA phosphorylated was proportional to the concentration of 'ArcB. Thus, 'ArcB acted as a kinase for ArcA. Chemical stabilities of the phosphorylated proteins suggested that 'ArcB-32P contained both a histidyl phosphate and an aspartyl phosphate(s) and that ArcA-32P contained only an aspartyl phosphate(s). PMID- 1512199 TI - Characterization of aromatic dehalogenases of Mycobacterium fortuitum CG-2. AB - Two different dehalogenation enzymes were found in cell extracts of Mycobacterium fortuitum CG-2. The first enzyme was a halophenol para-hydroxylase, a membrane associated monooxygenase that required molecular oxygen and catalyzed the para hydroxylation and dehalogenation of chlorinated, fluorinated, and brominated phenols to the corresponding halogenated hydroquinones. The membrane preparation with this activity was inhibited by cytochrome P-450 inhibitors and also showed an increase in the A448 caused by CO. The second enzyme hydroxylated and reductively dehalogenated tetrahalohydroquinones to 1,2,4-trihydroxybenzene. This halohydroquinone-dehalogenating enzyme was soluble, did not require oxygen, and was not inhibited by cytochrome P-450 inhibitors. PMID- 1512200 TI - Growth inhibition and loss of virulence in cultures of Agrobacterium tumefaciens treated with acetosyringone. AB - Acetosyringone, a phenolic inducer of the virulence (vir) genes of Agrobacterium tumefaciens, inhibited the growth of the nopaline-type strains T37 and C58 incubated under acidic conditions. In the course of a 6-day incubation with acetosyringone, avirulent clones were produced in different proportions by strains T37 and C58 and also by a spontaneous variant of strain C58, denominated C58F. The proportion of avirulent clones in acetosyringone-treated cultures often exceeded 50% for strains T37 and C58F and was of the order of 1% for strain C58. Control cultures not exposed to acetosyringone did not yield avirulent clones. Two other vir inducers, sinapinic acid and syringaldehyde, also inhibited growth and promoted accumulation of avirulent clones in cultures of strains C58F and T37. On the other hand, various acetosyringone analogs reported not to induce the vir genes did not act as growth inhibitors. All of the T37 and most of the C58F avirulent clones examined still carried a Ti plasmid. In all instances examined, avirulent clones still carrying a Ti plasmid were mutated in this plasmid. Mutants of strain C58F lacked the capacity to induce a virB::lacZ fusion in the presence of acetosyringone. PMID- 1512201 TI - A novel lactococcal bacteriocin whose activity depends on the complementary action of two peptides. AB - A lactococcal bacteriocin, termed lactococcin G, was purified to homogeneity by a simple four-step purification procedure that includes ammonium sulfate precipitation, binding to a cation exchanger and octyl-Sepharose CL-4B, and reverse-phase chromatography. The final yield was about 20%, and nearly a 7,000 fold increase in the specific activity was obtained. The bacteriocin activity was associated with three peptides, termed alpha 1, alpha 2, and beta, which were separated by reverse-phase chromatography. Judging from their amino acid sequences, alpha 1 and alpha 2 were the same gene product. Differences in their configurations presumably resulted in alpha 2 having a slightly lower affinity for the reverse-phase column than alpha 1 and a reduced bacteriocin activity when combined with beta. Bacteriocin activity required the complementary action of both the alpha and the beta peptides. When neither alpha 1 nor beta was in excess, about 0.3 nM alpha 1 and 0.04 nM beta induced 50% growth inhibition, suggesting that they might interact in a 7:1 or 8:1 ratio. As judged by the amino acid sequence, alpha 1 has an isoelectric point of 10.9, an extinction coefficient of 1.3 x 10(4) M-1 cm-1, and a molecular weight of 4,346 (39 amino acid residues long). Similarly, beta has an isoelectric point of 10.4, an extinction coefficient of 2.4 x 10(4) M-1 cm-1, and a molecular weight of 4110 (35 amino acid residues long). Molecular weights of 4,376 and 4,109 for alpha 1 and beta, respectively, were obtained by mass spectrometry. The N-terminal halves of both the alpha and beta peptides may form amphiphilic alpha-helices, suggesting that the peptides are pore-forming toxins that create cell membrane channels through a "barrel-stave" mechanism. The C-terminal halves of both peptides consist largely of polar amino acids. PMID- 1512203 TI - The acyl dihydroxyacetone phosphate pathway enzymes for glycerolipid biosynthesis are present in the yeast Saccharomyces cerevisiae. AB - The presence of the acyl dihydroxyacetone phosphate (acyl DHAP) pathway in yeasts was investigated by examining three key enzyme activities of this pathway in Saccharomyces cerevisiae. In the total membrane fraction of S. cerevisiae, we confirmed the presence of both DHAP acyltransferase (DHAPAT; Km = 1.27 mM; Vmax = 5.9 nmol/min/mg of protein) and sn-glycerol 3-phosphate acyltransferase (GPAT; Km = 0.28 mM; Vmax = 12.6 nmol/min/mg of protein). The properties of these two acyltransferases are similar with respect to thermal stability and optimum temperature of activity but differ with respect to pH optimum (6.5 for GPAT and 7.4 for DHAPAT) and sensitivity toward the sulfhydryl blocking agent N ethylmaleimide. Total membrane fraction of S. cerevisiae also exhibited acyl/alkyl DHAP reductase (EC 1.1.1.101) activity, which has not been reported previously. The reductase has a Vmax of 3.8 nmol/min/mg of protein for the reduction of hexadecyl DHAP (Km = 15 microM) by NADPH (Km = 20 microM). Both acyl DHAP and alkyl DHAP acted as substrates. NADPH was the specific cofactor. Divalent cations and N-ethylmaleimide inhibited the enzymatic reaction. Reductase activity in the total membrane fraction from aerobically grown yeast cells was twice that from anaerobically grown cells. Similarly, DHAPAT and GPAT activities were also greater in aerobically grown yeast cells. The presence of these enzymes, together with the absence of both ether glycerolipids and the ether lipid-synthesizing enzyme (alkyl DHAP synthase) in S. cerevisiae, indicates that non-ether glycerolipids are synthesized in this organism via the acyl DHAP pathway. PMID- 1512202 TI - Environmental regulation of virulence in group A streptococci: transcription of the gene encoding M protein is stimulated by carbon dioxide. AB - We have found that different atmospheres can have significant effects on the transcription of emm, the gene that encodes M protein, the major virulence factor of the group A streptococcus (Streptococcus pyogenes). Expression of emm was monitored by constructing a transcriptional fusion of the promoter for emm6.1 from S. pyogenes JRS4 to a promoterless chloramphenicol acetyltransferase gene. Transcription, as measured by determining chloramphenicol acetyltransferase specific activity, was stimulated by as much as 25-fold by increased carbon dioxide tension. Expression was greater in the latter stages of growth and was not affected by growth at 30 instead of 37 degrees C. Insertional inactivation of mry, a gene encoding a positive regulator of emm6.1, reduced chloramphenicol acetyltransferase activity below the detectable level. We conclude that expression of emm is influenced by environmental factors and that the level of carbon dioxide is one signal that may influence expression of M protein during infection. PMID- 1512204 TI - Characterization of the archaeal, plasmid-encoded type II restriction modification system MthTI from Methanobacterium thermoformicicum THF: homology to the bacterial NgoPII system from Neisseria gonorrhoeae. AB - A restriction-modification system, designated MthTI, was localized on plasmid pFV1 from the thermophilic archaeon Methanobacterium thermoformicicum THF. The MthTI system is a new member of the family of GGCC-recognizing restriction modification systems. Functional expression of the archaeal MthTI genes was obtained in Escherichia coli. The mthTIR and mthTIM genes are 843 and 990 bp in size and code for proteins of 281 (32,102 Da) and 330 (37,360 Da) amino acids, respectively. The deduced amino acid sequence of M.MthTI showed high similarity with that of the isospecific methyltransferases M.NgoPII and M.HaeIII. In addition, extensive sequence similarity on the amino acid level was observed for the endonucleases R.MthTI and R.NgoPII. Moreover, the endonuclease and methyltransferase genes of the thermophilic MthTI system and those of the Neisseria gonorrhoeae NgoPII system show identical organizations and high (54.5%) nucleotide identity. This finding suggests horizontal transfer of restriction modification systems between members of the domains Bacteria and Archaea. PMID- 1512205 TI - Isolation and characterization of Pseudomonas aeruginosa mutants blocked in the synthesis of pyoverdin. AB - We have isolated and characterized by chemical and enzymatic analyses three distinct types of pyoverdin-defective (pvd) mutants of Pseudomonas aeruginosa PAO1. The pvd-1 mutant is an L-N5-hydroxyornithine (L-N5-OH-Orn) auxotroph unable to hydroxylate L-ornithine (L-Orn) in a cell-free system and requiring L-N5-OH Orn for pyoverdin production. The other two types of mutants appear to be blocked in further steps of the biosynthetic pathway leading to pyoverdin, namely, the acylation of L-N5-OH-Orn (pvd-2) and chromophore synthesis (pvd-3). The different pvd mutations were all found to be located in the catA1 region at 47 min of the genetic map of P. aeruginosa PAO1. PMID- 1512207 TI - Tandem cloning of bacteriophage T4 nrdA and nrdB genes and overproduction of ribonucleoside diphosphate reductase (alpha 2 beta 2) and a mutationally altered form (alpha 2 beta 2(93)). AB - To investigate the role of ribonucleoside diphosphate reductase in the deoxyribonucleoside triphosphate synthetase multienzyme complex induced by bacteriophage T4 infection and to study the expression of the T4 nrdA and nrdB genes, we have constructed separate plasmid expression strains overproducing their respective alpha 2 and beta 2 protein products. Because complementation of the two proteins to form an active alpha 2 beta 2 enzyme presented complications, nrdA and nrdB, each with its own tac promoter, were also cloned in tandem into a single expression vector. The resulting plasmid (pnrdAB) overproduces ribonucleoside diphosphate reductase. Phage T4 nrdB93, described by Wirak et al. (D. O. Wirak, K. S. Cook, and G. R. Greenberg, J. Biol. Chem. 263:6193-6201, 1988) contains a lesion in exon II of the gene. The mutation causes not only a temperature-sensitive inactivation of the catalytic structure of the beta 2(93) protein and of its ability to interact with alpha 2 protein to form the alpha 2 beta 2(93) enzyme but also a profound non-temperature-sensitive decrease in the formation of the beta 2(93) protein. An expression vector overproducing active alpha 2 beta 2(93) was constructed by site-directed mutagenesis of the nrdB gene. PMID- 1512206 TI - Behavioral analysis of Vibrio parahaemolyticus variants in high- and low viscosity microenvironments by use of digital image processing. AB - Digital image analysis and light microscopy were used to study and quantify the growth and behavior of two variants and selected flagellar mutants of Vibrio parahaemolyticus in glass flow cells under high- and low-viscosity conditions. The observations showed a series of surface-associated behaviors, including attachment, microcolony formation, migration, chemotactic movements, and aggregation, indicating a substantial degree of adaptive flexibility and multicellular behavior during growth of V. parahaemolyticus at interfaces. PMID- 1512208 TI - Confirmation of oxidative dehalogenation of pentachlorophenol by a Flavobacterium pentachlorophenol hydroxylase. AB - Pentachlorophenol (PCP) hydroxylase purified from Flavobacterium sp. strain ATCC 39723 converted PCP or 2,3,5,6-tetrachlorophenol to tetrachloro-p-hydroquinone (TeCH) with the co-consumption of O2 and NADPH. The purified enzyme incorporated 18O from 18O2 but not from H218O into the reaction end product TeCH. The results clearly demonstrate that PCP is oxidatively converted to TeCH by a monooxygenase type enzyme from Flavobacterium sp. strain ATCC 39723. PMID- 1512210 TI - Location of the metA gene on the physical map of Escherichia coli. PMID- 1512209 TI - Cloning and sequencing of Escherichia coli murZ and purification of its product, a UDP-N-acetylglucosamine enolpyruvyl transferase. AB - The Escherichia coli gene murZ, encoding the enzyme UDP-N-acetylglucosamine enolpyruvyl transferase, has been cloned and sequenced. Identified by screening an E. coli genomic library for clones that conferred phosphomycin resistance, murZ encoded a 419-amino-acid polypeptide and was mapped to 69.3 min on the E. coli chromosome. MurZ protein was purified to near homogeneity and found to have the expected UDP-N-acetylglucosamine enolpyruvyl transferase activity. Sequence analysis of the predicted product revealed 44% identity to OrfR from Bacillus subtilis (K. Trach, J.W. Chapman, P. Piggot, D. LeCoq, and J.A. Hoch, J. Bacteriol. 170:4194-4208, 1988), suggesting that orfR may also encode a UDP-N acetylglucosamine enolpyruvyl transferase enzyme. MurZ is also homologous to the aromatic amino acid biosynthetic enzyme enolpyruvyl shikimate phosphate synthase, the other enzyme known to catalyze an enolpyruvyl transfer. PMID- 1512211 TI - Location of the nupC gene on the physical map of Escherichia coli K-12. PMID- 1512212 TI - Localization of the ferredoxin (fdx) gene on the physical map of the Escherichia coli chromosome. PMID- 1512213 TI - Location of the ubiA gene on the physical map of Escherichia coli. PMID- 1512214 TI - An essential gene (efg) located at 38.1 minutes on the Escherichia coli chromosome. PMID- 1512215 TI - Phosphorylation of eukaryotic initiation factor (eIF) 2 alpha and inhibition of eIF-2B in GH3 pituitary cells by perturbants of early protein processing that induce GRP78. AB - Agents that mobilize sequestered intracellular Ca2+, including ionophore A23187, EGTA, thapsigargin, and Cbz-Gly-Phe-NH2 (where Cbz is benzyloxycarbonyl), or mild reducing agents, such as dithiothreitol, disrupt early protein processing in the endoplasmic reticulum (ER), inhibit translational initiation, and trigger the induction of GRP78, an ER resident protein. Inhibition of translational initiation in response to acute treatment (15-30 min) of intact GH3 pituitary cells with each of these agents was accompanied by an average 5-fold increase in the amount of phosphorylated eukaryotic initiation factor (eIF) 2 alpha and a 50% reduction in eIF-2B activity. With continued exposure to A23187 (3 h) rates of amino acid incorporation partially recovered, eIF-2 alpha became dephosphorylated, and the inhibition of eIF-2B activity was abolished. These chronic effects were blocked by actinomycin D. Accumulating evidence that the ER may regulate rates of translational initiation through a signaling system altering the activity of eIF-2 is discussed. PMID- 1512216 TI - Site-directed mutagenesis of the phosphorylatable serine (Ser8) in C4 phosphoenolpyruvate carboxylase from sorghum. The effect of negative charge at position 8. AB - The properties of the dephospho and in vitro phosphorylated forms of recombinant sorghum phosphoenolpyruvate carboxylase have been compared with those of the authentic dark (dephospho) and light (phospho) leaf enzyme forms and two mutant enzymes in which the phosphorylatable serine residue (Ser8) has been changed by site-directed mutagenesis to Cys (S8C) or Asp (S8D). Kinetic analysis of the purified recombinant, mutant, and leaf enzyme forms at pH 8.0 indicated virtually identical Vmax, apparent Km (phosphoenolpyruvate), and half-maximal activation (glucose 6-P) values of about 44 units/mg, 1.1 mM, and 0.23 mM, respectively. In contrast, the Ser8, S8C, and dark leaf enzymes were about 3-fold more sensitive to inhibition by L-malate at pH 7.3 than the Ser8-P, S8D, and light leaf enzyme forms. These comparative results indicate that: (i) Ser8 is an important determinant in the regulation of sorghum phosphoenolpyruvate carboxylase activity by negative (L-malate), but not positive (glucose 6-phosphate) metabolite effectors, (ii) phosphorylation of this target residue can be functionally mimicked by Asp, but not Cys, and (iii) negative charge contributes to the effect of regulatory phosphorylation on this C4-photosynthesis enzyme. PMID- 1512217 TI - Reconstitution of neutrophil NADPH oxidase activity in the cell-free system by four components: p67-phox, p47-phox, p21rac1, and cytochrome b-245. AB - Activation of the NADPH oxidase of phagocytes in the cell-free system requires the association of several cytosolic components with membrane-bound cytochrome b. In this study we were able to fully reconstitute NADPH oxidase activity in the cell-free system with three recombinant proteins: p67-phox, p47-phox, p21rac1, and pure cytochrome b-245. Activity was dependent upon the concentration of the proteins, with maximal activity observed with roughly equimolar ratios of the cytochrome b and p67-phox (133 and 163 mol/s/mol, respectively) and concentrations of the other two proteins approximately 1 order of magnitude greater. No activity was observed in the absence of any one of these components. In addition, activation was dependent upon p21rac1 being preloaded with GTP, the cytochrome b being reconstituted with lipid, and the presence of FAD during activation. Half-maximal activity was observed at a concentration of NADPH of approximately 50 microM. These findings confirm our recent description of the membrane-bound cytochrome b as a FAD-containing flavocytochrome b containing the NADPH binding site, and implicate the three cytosolic proteins in its activation. PMID- 1512218 TI - Nitric oxide causes ADP-ribosylation and inhibition of glyceraldehyde-3-phosphate dehydrogenase. AB - Nitric oxide and nitric oxide-generating agents like 3-morpholinosydnonimine (SIN 1) stimulate the mono-ADP-ribosylation of a cytosolic, 39-kDa protein in various tissues. This protein was purified from human platelet cytosol by conventional and fast protein liquid chromatography techniques. N-terminal sequence analysis identified the isolated protein as the glycolytic enzyme glyceraldehyde-3 phosphate dehydrogenase (GAPDH). Nitric oxide stimulates the auto-ADP ribosylation of GAPDH in a time and concentration-dependent manner with maximal effects after about 60 min. Associated with ADP-ribosylation is a loss of enzymatic activity. NAD(+)-free enzyme is not inhibited by SIN-1, indicating the absolute requirement of NAD+ as the substrate of the ADP-ribosylation reaction. Inhibition of the glycolytic enzyme GAPDH may be relevant as a cytotoxic effect of NO complementary to its inhibitory actions on iron-sulfur enzymes like aconitase and electron transport proteins of the respiratory chain. PMID- 1512219 TI - The chromosome origin of Escherichia coli stabilizes DnaA protein during rejuvenation by phospholipids. AB - DnaA protein (the initiator protein) binds and clusters at the four DnaA boxes of the Escherichia coli chromosomal origin (oriC) to promote the strand opening for DNA replication. DnaA protein activity depends on the tight binding of ATP; the ADP form of DnaA protein, generated by hydrolysis of the bound ATP, is inactive. Rejuvenation of ADP-DnaA protein, by replacement with ATP, is catalyzed by acidic phospholipids in a highly fluid bilayer. We find that interaction of DnaA protein with oriC DNA is needed to stabilize DnaA protein during this rejuvenation process. Whereas DnaA protein bound to oriC DNA responds to phospholipids, free DnaA protein is inactivated by phospholipids and then fails to bind oriC. Furthermore, oriC DNA facilitates the high affinity binding of ATP to DnaA protein during treatment with phospholipids. A significant portion of the DnaA protein associated with oriC DNA can be replaced by the ADP form of the protein, suggesting that all of the DnaA protein bound to oriC DNA need not be rejuvenated between rounds of replication. PMID- 1512220 TI - trp repressor/trp operator interaction. Equilibrium and kinetic analysis of complex formation and stability. AB - The trp repressor of Escherichia coli regulates transcription initiation in the trp operon by binding at an operator located within the trp promoter region. We have used a filter binding assay to analyze the interaction between purified trp repressor and a synthetic 43-base pair DNA fragment containing the natural trp promoter-operator region. In equilibrium binding experiments, the KD of high affinity binding of trp repressor to this DNA fragment was determined to be 2 x 10(-10) M. Low affinity binding was observed at repressor concentrations above 10 nM. In kinetic experiments with various input ratios of repressor to operator, trp repressor-operator complexes dissociated with equivalent, first-order kinetics. Instantaneous reduction of the tryptophan concentration resulted in increased rates of complex dissociation, indicating that loss of one or both tryptophan molecules from the repressor-operator complex destabilizes the complex. A heterodimeric repressor with a single tryptophan binding site was constructed and its affinity for operator was compared with that of ligand free aporepressor and tryptophan saturated repressor. The heterodimeric repressor had a 20-25-fold higher affinity for operator than did the aporepressor, and it had a 20-25-fold lower affinity for operator than did the tryptophan-saturated repressor. PMID- 1512222 TI - Effects of amino-terminal extensions and specific mutations on the activity of restrictocin. AB - The cytotoxic activities of restrictocin with aminoterminal extensions and specific mutations were investigated using in vivo and in vitro systems. Genes were constructed from the cDNA clone of restrictocin which encode: the native form of restrictocin (including the leader sequence); Met-prorestrictocin, in which a codon for methionine was placed before a putative pro region; Met-mature restrictocin, with a methionine codon prior to the mature form of restrictocin; and three mutated forms of Met-mature restrictocin, E95G, E115G/H136L, and H136L. These constructions were placed under the control of the GAL1 promoter and were transformed into Saccharomyces cerevisiae. Transformants were killed, and a new RNA band formed when any of these genes except those containing the H136L mutation were expressed. Restrictocin protein was detected by immunoblot only in cells expressing the native form of restrictocin and the forms containing the H136L mutation. Native restrictocin, Met-prorestrictocin, and Met-mature restrictocin mRNA were translated in an in vitro system resulting in proteins of the expected molecular weight and inactivation of the translation system. Restrictocin was not inactivated by the presence of the leader sequence and the putative prosequence. Amino acid His136 is putatively in the active site of restrictocin by analogy to ribonuclease U2 and the elimination of toxic effects in the S. cerevisiae expression and in vitro translation systems. PMID- 1512221 TI - On the mechanism of the mitochondrial decarboxylation of phosphatidylserine. AB - To study intramitochondrial phospholipid flow, radiolabeled phosphatidylserine was introduced into isolated rat liver mitochondria from donor vesicles through the action of a nonspecific lipid transfer protein. Imported phosphatidylserine was rapidly decarboxylated to phosphatidylethanolamine. Both the imported phosphatidylserine and the formed phosphatidylethanolamine were confined to the outer membrane. The enzyme phosphatidylserine decarboxylase was shown to be located exclusively in the inner membrane. It was not enriched in isolated contact site fractions. 1,4-Dinitrophenol caused an inhibition of the decarboxylation of phosphatidylserine. This inhibition was not due to the uncoupling of the oxidative phosphorylation itself, but possibly due to a decrease in the number of contact sites. This suggests that phosphatidylserine flows from the outer membrane to the inner membrane through contact sites between inner and outer membrane to become decarboxylated and that the formed phosphatidylethanolamine flows directly back to the outer membrane, without mixing with inner membrane phosphatidylethanolamine. PMID- 1512223 TI - Biological activity of a proteoglycan form of macrophage colony-stimulating factor and its binding to type V collagen. AB - Two different types of macrophage colony-stimulating factors (M-CSF) were found, one with an apparent molecular mass of 85 kDa and the other greater than 200 kDa. The high molecular mass M-CSF was identified as a proteoglycan carrying chondroitin sulfate glycosaminoglycan and was designated as the proteoglycan form of M-CSF (PG-M-CSF). In this study, we compared the biological activity of the 85 kDa M-CSF and PG-M-CSF and examined the binding properties of these two M-CSF to certain extracellular matrix proteins, i.e. types I-V collagen and fibronectin, using a modified enzyme-linked immunosorbent assay. PG-M-CSF was capable of supporting the formation of murine macrophage colonies, and pretreatment of PG-M CSF with chondroitinase AC, which degrades chondroitin sulfate, did not alter its colony-stimulating activity. The specific activity of PG-M-CSF was similar to that of the 85-kDa M-CSF. The 85-kDa M-CSF had no apparent affinity for the extracellular matrix proteins examined, whereas PG-M-CSF had an appreciable binding capacity to type V collagen, but did not bind to types I, II, III, and IV collagen or to fibronectin. Pretreatment of PG-M-CSF with chondroitinase AC completely abolished the binding of the species to type V collagen. Addition of exogenous chondroitin sulfate inhibited the binding of PG-M-CSF to type V collagen in a dose-dependent manner. These data indicated that the interaction between PG-M-CSF and type V collagen was mediated by the chondroitin sulfate chain of PG-M-CSF. PG-M-CSF bound to type V collagen could stimulate the proliferation of bone marrow macrophages, indicating that the matrix protein bound PG-M-CSF retained its biological activity. This interaction between PG-M CSF and type V collagen implies that the role of PG-M-CSF may be distinct from that of 85-kDa M-CSF. PMID- 1512224 TI - Localization of the cAMP-dependent protein kinase to the postsynaptic densities by A-kinase anchoring proteins. Characterization of AKAP 79. AB - Postsynaptic densities (PSD) are a network of proteins located on the internal surface of excitatory synapses just inside the postsynaptic membrane. Enzymes associated with the PSD are optimally positioned to respond to signals transduced across the postsynaptic membrane resulting from excitatory synaptic transmission or neurotransmitter release. We present evidence suggesting that type II cAMP dependent protein kinase (PKA) is anchored to the PSD through interaction of its regulatory subunit (RII) with an A-Kinase Anchor Protein (AKAPs). A cDNA for the human RII-anchoring protein, AKAP 79, was isolated by screening an expression library with radiolabeled RII. This cDNA (2621 base pairs) encodes a protein of 427 amino acids with 76% identity to bovine brain AKAP 75 and 93% identity to a carboxyl-terminal RII-binding fragment of murine brain AKAP 150. A bacterially expressed 92-amino acid fragment, AKAP 79 (335-427) was able to bind RII alpha. Disruption of secondary structure by site-directed mutagenesis at selected residues within a putative acidic amphipathic helix located between residues 392 and 408 prevented RII binding. Immunological studies demonstrate that AKAP 79 is predominantly expressed in the cerebral cortex and is a component of fractions enriched for postsynaptic densities. AKAP antisera strongly cross-react with a 150-kDa protein in murine PSD believed to be AKAP 150. Co-localization of the type II PKA in purified PSD fractions was confirmed immunologically by detection of RII and enzymologically by measuring cAMP-stimulated phosphorylation of the heptapeptide substrate Kemptide. Approximately 30% of the PSD kinase activity was specifically inhibited by PKI 5-24 peptide, a highly specific inhibitor of PKA. We propose that AKAP 79 and AKAP 150 function to anchor the type II PKA to the PSD, presumably for a role in the regulation of postsynaptic events. PMID- 1512227 TI - Human immunodeficiency virus type 1 induces 1-beta-D-arabinofuranosylcytosine resistance in human H9 cell line. AB - We have found that chronically HIV-1(IIIB)-infected H9 cells showed 21-fold resistance to 1-beta-D-arabinofuranosylcytosine (ARA-C) compared with uninfected H9 cells. In the infected H9 cells, a 37% increase of dCTP pool and a 34% increase of dATP were observed, and no alteration of dTTP and dGTP was observed, compared with the uninfected H9 cells. A marked decrease of ARA-CTP generation was observed in the infected H9 cells after 3-h incubation with 0.1-10 microM ARA C. The level of deoxycytidine kinase activity with ARA-C as substrate was similar in both the infected and the uninfected cells; however, a 37-fold increase of cytidine deaminase activity was observed in the infected H9 cells. These results indicate that the induction of cytidine deaminase activity by HIV-1(IIIB) infection conferred ARA-C resistance to H9 cells. This conclusion was supported by the observation that a marked reversal of ARA-C resistance in the infected H9 cells occurred after treatment with the inhibitor of cytidine deaminase, 3,4,5,6 tetrahydrouridine. The understanding of these cellular alterations in drug sensitivity may facilitate the development of effective therapeutic strategies against HIV-1-infected cells. PMID- 1512225 TI - Effect of the thermostable protein kinase inhibitor on intracellular localization of the catalytic subunit of cAMP-dependent protein kinase. AB - cAMP-dependent protein kinase mediates a variety of cellular responses in most eukaryotic cells. Many of these responses are cytoplasmic, whereas others appear to require nuclear localization of the catalytic subunit. In order to understand further the molecular basis for subcellular localization of the catalytic subunit, the effect of the heat stable protein kinase inhibitor (PKI) was investigated. The subcellular localization of the catalytic (C) subunit was determined both in the presence and absence of PKI, by microinjecting fluorescently labeled C subunit into single living cells. When injected alone, a significant fraction of the dissociated C subunit localized to the nucleus. When coin-injected with an excess of PKI, little of the C subunit localized to the nucleus, suggesting that accumulation of catalytic subunit in the nucleus requires either enzymatic activity or a nuclear localization signal. Inactivation of the catalytic subunit in vitro by treatment with N-ethylmaleimide did not prevent localization in the nucleus, indicating that enzymatic activity was not a prerequisite for nuclear localization. In an effort to search for a specific signal that might mediate nuclear localization, a complex of the catalytic subunit with a 20-residue inhibitory peptide derived from PKI (PKI(5-24)) was microinjected. In contrast to intact PKI, the peptide was not sufficient to block nuclear accumulation. In the presence of PKI(5-24), the C subunit localized to the nucleus in a fashion analogous to that of dissociated, active C subunit despite evidence of no catalytic activity in situ. Thus, nuclear localization of the C subunit appears to be independent of enzymatic activity but most likely dependent upon a signal. The signal is apparently masked by both the regulatory subunit and PKI but not by the inhibitory peptide. PMID- 1512226 TI - Molecular species analysis of a product of phospholipase D activation. Phosphatidylethanol is formed from phosphatidylcholine in phorbol ester- and bradykinin-stimulated PC12 cells. AB - Tumor-promoting phorbol esters or calcium-mobilizing receptor ligands stimulate phosphatidylcholine breakdown and in many cells this is accompanied by phospholipase D (PLD) activation. We tested whether or not a direct relationship exists between these two phenomena. Pheochromocytoma (PC12) cells were stimulated with the phorbol ester 12-O-tetradecanoyl-phorbol-13-acetate or with the calcium mobilizing receptor ligand bradykinin in media containing 1% ethanol. The fatty acid composition of the molecular species of phosphatidylethanol (PEt), a product of PLD activation, formed in stimulated cells was compared with the molecular species of endogenous phospholipids isolated from unstimulated PC12 cells. PEt was isolated and analyzed by fast atom bombardment-mass spectrometry (FAB-MS) in the negative ion mode. Fatty acid composition and headgroup structure of the major PEt molecular ions were confirmed by linked scan analysis. Phosphatidylcholine, phosphatidylethanolamine, phosphatidylserine, and phosphatidylinositol were isolated from unstimulated cells and converted into phosphatidic acids using PLD. Mass spectra of the respective phosphatidic acids were obtained by fast atom bombardment-mass spectrometry as described above. The molecular species of PEt formed in 12-O-tetradecanoylphorbol-13-acetate- and bradykinin-stimulated PC12 cell were identical to those of phosphatidylcholine isolated from untreated cells. PMID- 1512228 TI - Identification of phosphatidylcholine-selective and phosphatidylinositol selective phospholipases D in Madin-Darby canine kidney cells. AB - Intact cells and cell-free systems were employed to characterize phospholipase D (PLD) activity in Madin-Darby canine kidney (MDCK) cells. In cells prelabeled with [3H]glycerol, 12-O-tetradecanoylphorbol-13-acetate (TPA) elicited phosphatidylcholine (PC) hydrolysis by PLD, as shown by the prolonged formation of [3H]phosphatidylethanol (PEt) and an accompanying decrease in [3H]PC. In contrast, bradykinin elicited rapid formation of [3H]PEt (approximately 1 min) accompanied by a decrease in [3H]phosphatidylinositol (PI). When the agonists were administered simultaneously, [3H]PEt formation was biphasic. In cells prelabeled with [3H] choline, at times less than 1 min, bradykinin failed to induce significant change in [3H]choline release. Bradykinin-induced formation of [3H]PEt in the [3H]glycerol-labeled cells was strictly dependent on extracellular Ca2+, whereas TPA-induced formation of [3H]PEt did not require extracellular Ca2+. Cell-free assays for PLD were used to assess the enzyme location, substrate specificity, and cofactor requirements. The PC-PLD activity (PEt formation) against [3H]stearoyl-PC was primarily localized in the 440 x g pellet (membrane- and nuclear-associated), preferred PC as a substrate, required detergent, and was not influenced by Ca2+ at low concentrations but was inhibited by Ca2+ in excess of 0.5 mM. The PI-PLD activity against [3H]stearoyl-PI was found largely in the 100,000 x g supernatant (cytosol), was strictly Ca(2+)-dependent, and did not require detergent. From these data, we conclude that MDCK cells contain two PLD subtypes: 1) a membrane-associated, PC-selective enzyme that responds to TPA resulting in prolonged hydrolysis of PC (the PC-PLD is Ca(2+)-independent, but requires detergent); 2) a cytosolic, PI-selective enzyme that responds rapidly but transiently to bradykinin (the PI-PLD requires Ca2+ but not detergent). PMID- 1512229 TI - Hormonal regulation of cholesterol 7 alpha-hydroxylase mRNA levels and transcriptional activity in primary rat hepatocyte cultures. AB - In primary cultures of adult rat hepatocytes the level of cholesterol 7 alpha hydroxylase steady-state mRNA markedly decreased by 72 h. However, the addition of L-thyroxine (T4) and dexamethasone synergistically returned cholesterol 7 alpha-hydroxylase steady-state mRNA levels near to that of cholestyramine-fed animals. The maximal responses to T4 and dexamethasone in serum-free medium were at 1.0 and 0.1 microM, respectively. The addition of T4 in combination with dexamethasone resulted in an 11-fold increase in transcriptional activity of the cholesterol 7 alpha-hydroxylase gene as compared to no addition controls. The specific activities of cholesterol 7 alpha-hydroxylase in microsomes prepared from cultures treated with dexamethasone and T4 were 1.56 +/- 1.17 nmol/h/mg protein which is similar to that of intact liver (1.70 +/- 0.062 nmol/h/mg protein), but lower than cholestyramine-fed animals. Cholesterol 7 alpha hydroxylase activity was not detectable (less than 0.020 nmol/h/mg protein) at 72 h in cultures without the addition of both dexamethasone and T4. In the presence of optimal concentrations of dexamethasone and T4, glucagon (0.2 microM), or dibutyryl cAMP (50 microM) decreased (90%) cholesterol 7 alpha-hydroxylase mRNA within 6 h. Transcriptional activity decreased (62%) in 6 h following the addition of glucagon (0.2 microM) to the culture medium. The results reported in this paper suggest an important role for multiple hormones in the regulation of cholesterol 7 alpha-hydroxylase in the liver. PMID- 1512230 TI - A recombinant form of Pseudomonas exotoxin directed at the epidermal growth factor receptor that is cytotoxic without requiring proteolytic processing. AB - Pseudomonas exotoxin A is composed of three structural domains that mediate cell recognition (I), membrane translocation (II), and ADP-ribosylation (III). Within the cell, the toxin is cleaved within domain II to produce a 37-kDa carboxyl terminal fragment, containing amino acids 280-613, which is translocated to the cytosol and causes cell death. In this study, we constructed a mutant protein (PE37), composed of amino acids 280-613 of Pseudomonas exotoxin A, which does not require proteolysis to translocate. PE37 was targeted specifically to cells with epidermal growth factor receptors by inserting transforming growth factor-alpha (TGF-alpha) after amino acid 607 near the carboxyl terminus of Pseudomonas exotoxin A. PE37/TGF-alpha was very cytotoxic to cells with epidermal growth factor receptors. It was severalfold more cytotoxic than a derivative of full length Pseudomonas exotoxin A containing TGF-alpha in the same position, probably because the latter requires intracellular proteolytic processing to exhibit its cytotoxicity, and proteolytic processing is not 100% efficient. Deletion of 2, 4, or 7 amino acids from the amino terminus of PE37/TGF-alpha greatly diminished cytotoxic activity, indicating the need for a proper amino-terminal sequence. In addition, a mutant containing an internal deletion of amino acids 314-380 was minimally active, indicating that other regions of domain II are also required for the cytotoxic activity of Pseudomonas exotoxin A. PMID- 1512231 TI - Palmitylation of a G-protein coupled receptor. Direct analysis by tandem mass spectrometry. AB - Bovine rhodopsin has been reported to be S-palmitylated at cysteines 322 and 323 (Ovchinnikov, Y. A., Abdulaev, N. G., and Bogachuk, A.S. (1988) FEBS Lett. 230, 1 5). Using a combination of enzymatic and chemical cleavage techniques in conjunction with tandem mass spectrometry, the sites of incorporation of the palmityl groups are shown. Bovine rhodopsin in disc membranes was digested with thermolysin to generate the C-terminal fragment (241-327), which was subsequently cleaved with cyanogen bromide to generate the peptide Val-Thr-Thr-Leu-Cys-Cys-Gly Lys-Asn-Pro (318-327). A bis-S-palmitylated synthetic standard had the same retention time by reversed-phase high performance liquid chromatography as the isolated peptide and the same molecular weight (MH+1511.7) by liquid secondary ion mass spectrometry. Dithiothreitol reduction of both the isolated and the synthetic peptide cleaved the two thioester-linked palmityl groups to produce reduction products of the same appropriately decreased molecular weight (MH+1035.5). Tandem mass spectrometry of the isolated and the synthetic peptide identified the sites of attachment of the palmityl groups on cysteines 322 and 323. These results prove the modification of cysteines 322 and 323 with palmitic acid in bovine rhodopsin, and illustrate the utility of mass spectrometry to characterize the post-translational modifications in G-protein coupled receptors. PMID- 1512232 TI - Localization of O-GlcNAc modification on the serum response transcription factor. AB - A unique form of nucleoplasmic and cytoplasmic protein glycosylation, O-linked GlcNAc, has previously been detected, using Gal transferase labeling techniques, on a myriad of proteins (for review see Hart, G. W., Haltiwanger, R. S., Holt, G. D., and Kelly, W. G. (1989a) Annu. Rev. Biochem. 58, 841-874), including many RNA polymerase II transcription factors (Jackson, S. P., and Tjian, R. (1988) Cell 55, 125-133). However, virtually nothing is known about the degree of glycosylation at individual sites, or, indeed, the actual sites of attachment of O-GlcNAc on transcription factors. In this paper we provide rigorous evidence for the occurrence and locations of O-GlcNAc on the c-fos transcription factor, serum response factor (SRF), expressed in an insect cell line. Fast atom bombardment mass spectrometry (FAB-MS) of proteolytic digests of SRF provides evidence for the presence of a single substoichiometric O-GlcNAc residue on each of four peptides isolated after sequential cyanogen bromide, tryptic, and proline specific enzyme digestion: these peptides are 306VSASVSP312, 274GTTSTIQTAP283, 313SAVSSADGTVLK324, and 374DSSTDLTQTSSSGTVTLP391. Using an array of techniques, including manual Edman degradation, aminopeptidase, and elastase digestion, together with FAB-MS, the major sites of O-GlcNAc attachment were shown to be serine residues within short tandem repeat regions. The highest level of glycosylation was found on the SSS tandem repeat of peptide (374-391) which is situated within the transcriptional activation domain of SRF. The other glycosylation sites observed in SRF are located in the region of the protein between the DNA binding domain and the transcriptional activation domain. Glycosylation of peptides (274-283) and (313-324) was found to occur on the serine in the TTST tandem repeat and on serine 316 in the SS repeat, respectively. The lowest level of glycosylation was recovered in peptide (306 312) which lacks tandem repeats. All the glycosylation sites identified in SRF are situated in a relatively short region of the primary sequence close to or within the transcriptional activation domain which is distant from the major sites of phosphorylation catalyzed by casein kinase II. PMID- 1512233 TI - Anion binding to the Schiff base of the bacteriorhodopsin mutants Asp-85--- Asn/Asp-212----Asn and Arg-82----Gln/Asp-85----Asn/Asp-212----Asn. AB - Studies of bacteriorhodopsin have indicated that the charge environment of the protonated Schiff base consists of residues Asp-85, Asp-212, and Arg-82. As shown recently (Marti, T., Rosselet, S. J., Otto, H., Heyn, M. P., and Khorana, H. G. (1991) J. Biol. Chem. 266, 18674-18683), in the double mutant Asp-85----Asn/Asp 212----Asn chromophore formation is restored in the presence of salts, suggesting that exogenous anions function as counterions to the protonated Schiff base. To investigate the role of Arg-82 and of the Schiff base in anion binding, we have prepared the triple mutant Arg-82----Gln/Asp-85----Asn/Asp-212----Asn and compared its properties with those of the Asp-85----Asn/Asp-212----Asn double mutant. Regeneration of the chromophore with absorption maximum near 560 nm occurs in the triple mutant in the presence of millimolar salt, whereas in the double mutant molar salt concentrations are required. Spectrometric titrations reveal that the pKa of Schiff base deprotonation is markedly reduced from 11.3 for the wild type to 4.9 for the triple mutant in 1 mM NaCl and to 5.5 for the double mutant in 10 mM NaCl. In both mutants, increasing the chloride concentration promotes protonation of the chromophore and results in a continuous rise of the Schiff base pKa, yielding a value of 8.4 and 7.6, respectively, in 4 M NaCl. The absorption maximum of the two mutants shows a progressive red shift, as the ionic radius of the halide increases in the sequence fluoride, chloride, bromide, and iodide. An identical spectral correlation in the presence of halides is observed for the acid-purple form of bacteriorhodopsin. We conclude, therefore, that upon neutralization of the two counterions Asp-85 and Asp-212 by mutation or by protonation at low pH, exogenous anions substitute as counterions by directly binding to the protonated Schiff base. This interaction may provide the basis for the proposed anion translocation by the acid-purple form of bacteriorhodopsin as well as by the related halorhodopsin. PMID- 1512234 TI - Single amino acid substitutions can convert the uncleaved signal-anchor of sucrase-isomaltase to a cleaved signal sequence. AB - A hydrophobic segment near the amino terminus (positions 12-32) of rabbit sucrase isomaltase functions both as a membrane anchor and as a signal sequence for translocation into the endoplasmic reticulum. Unlike most signal sequences, that of sucrase-isomaltase is not cleaved by signal peptidase. Using in vitro transcription and translation systems, we have found that substitution of a single proline, at position 28 or 29, converted the signal-anchor to a cleaved signal sequence, with cleavage occurring after alanine 26 and the introduced proline thereby occupying position +2 or +3 relative to the cleavage site. Two deletions that shorten the transmembrane domain by 8 amino acids were also effective, whereas various other changes upstream and downstream of this domain were without effect. We conclude that susceptibility to mammalian signal peptidase is influenced both by the length of the hydrophobic region and by the secondary structure downstream of the cleavage site. PMID- 1512235 TI - Biosynthesis of a nonphysiological sialic acid in different rat organs, using N propanoyl-D-hexosamines as precursors. AB - In this study it could be shown that in rat the normally occurring N-acetyl neuraminic acid can be modified in its N-acyl moiety by in vivo administration of the chemically synthesized N-propanoyl precursors, N-propanoyl-D-glucosamine or N propanoyl-D-mannosamine. It could be shown that each of these nonphysiological amino sugar analogues was incorporated into both membrane and serum glycoproteins. After treatment of rats with radiolabeled N-[acyl-1-14C]D mannosamine, radioactivity could be removed from serum glycoprotein fractions by incubation with neuraminidase from Clostridium perfringens or from Arthrobacter ureafaciens. Mild acid hydrolysis removed 98% of the radioactivity after in vivo labeling with N-[acetyl-1-14C]D-mannosamine and 86% after labeling with N [propanoyl-1-14C]D-mannosamine. Chromatographic analysis yielded two compounds, i.e. N-acetyl neuraminic acid and N-propanoyl neuraminic acid, the latter being identified by gas liquid chromatography/mass spectrometry studies. Measurement of protein-bound radioactivity in different rat organs revealed a different organotropy of the natural and the nonphysiological neuraminic acid precursor. Of the glucosamine derivatives, N-acetyl-D-glucosamine showed the higher rate of uptake and incorporation in most organs (except in the submandibulary gland), and especially in kidney cortex and Morris hepatoma 7777. Natural and the unphysiological mannosamine derivatives were incorporated at similar rates, except in liver, where N-acetyl-D-mannosamine was taken up and metabolized more effectively. This finding indicates that it is possible to modify the acyl group of N-acetyl neuraminic acid in vivo by the introduction of an N-propanoyl group and possibly other homologous N-acyl groups. This procedure may provide a tool for a further characterization of the biological function of sialic acids. PMID- 1512236 TI - Hepatic microsomal bilirubin UDP-glucuronosyltransferase. The kinetics of bilirubin mono- and diglucuronide synthesis. AB - Hepatic biotransformation of bilirubin to the hydrophilic species bilirubin mono- (BMG) and diglucuronide (BDG) by microsomal bilirubin UDP-glucuronosyl transferase (GT) is a prerequisite for its physiologic excretion into bile. The reaction mechanism of bilirubin-GT and the access of bilirubin and BMG (the intermediate substrate) to the active site of bilirubin-GT are undefined. Highly purified [14C]bilirubin and [3H] BMG were coincubated with rat liver microsomes, and the initial rates of radiolabeled bilirubin glucuronide synthesis were measured. Although these substrates differ markedly in their hydrophilicity, no significant differences were observed in [14C]- and [3H]BDG rates of formation from equimolar [14C]bilirubin and [3H] BMG, in the absence or presence of soluble binding proteins (albumin and hepatic cytosol). In further kinetic studies, [14C]bilirubin and [3H]BMG exhibited mutually competitive inhibition of [3H]- and [14C]BDG synthesis, respectively, and [3H]BMG also inhibited [14C]BMG formation. Finally, unlabeled BMG and BDG inhibited the glucuronidation of [14C]bilirubin, with all three pigments yielding virtual Michaelis-Menten dissociation constants in the 10-20 microM range. These findings indicate that: 1) bilirubin-GT follows Michaelis-Menten kinetics for both bilirubin and BMG glucuronidation over the range of substrate concentrations employed; 2) the findings are consistent with a single active site for the enzymatic synthesis of both BMG and BDG; 3) bilirubin, BMG, and BDG bind competitively to this active site with comparable affinities; and 4) access of both bilirubin and BMG substrates to the enzymatic active site is reduced by soluble binding proteins. PMID- 1512237 TI - L1210/B23.1 cells express equilibrative, inhibitor-sensitive nucleoside transport activity and lack two parental nucleoside transport activities. AB - Cultured mouse leukemia L1210 cells express the nucleoside-specific membrane transport processes designated es, ei, and cif. The es and ei processes are equilibrative, but may be distinguished by the high sensitivity of the former to 6-[(4-nitrobenzyl)thio]-9-beta-D-ribofuranosylpurine (NBMPR); the cif process is mediated by a Na+/nucleoside cotransporter of low sensitivity to NBMPR. Cells of an ei-deficient clonal line, L1210/MC5-1, were mutagenized, and clones were selected in soft agar medium that contained (i) NBMPR (an inhibitor of es processes), (ii) erythro-9-(2-hydorxy-3-nonyl)adenine (an inhibitor of adenosine deaminase), and (iii) arabinofuranosyladenine (a cytotoxic substrate for the three nucleotide transporters). The selection medium did not allow es activity and selected against cells that expressed the Na(+)-linked cif process. Cells of the L1210/B23.1 clonal isolate were deficient in cif transport activity, and inward fluxes of formycin B, a poorly metabolized analog of inosine, were virtually abolished by NBMPR in these cells. In the mutant cells, nonisotopic formycin B behaved as a countertransport substrate during influx of [3H]formycin B, and inward fluxes of the latter were competitively inhibited by purine and pyrimidine nucleosides. The transport behavior of L1210/B23.1 cells indicates that (i) the mutation/selection procedure impaired or deleted the Na(+)-linked cif process and (ii) es nucleoside transport activity is expressed in the mutant cells. PMID- 1512238 TI - Crystal structure of the unactivated form of ribulose-1,5-bisphosphate carboxylase/oxygenase from tobacco refined at 2.0-A resolution. AB - The structure of the unactivated form of ribulose-1,5-bisphosphate carboxylase/oxygenase was refined at a resolution of 2.0 A to an R-factor of 17.1%. The previous model (Chapman et al., 1988) was extensively rebuilt, and the small subunit was retraced. The refined model consists of residues 22-63 and 69 467 of the large subunit and the complete small subunit. A striking feature of the model is that several loops have very high B-factors, probably representing mobile regions of the molecule. An examination of the intersubunit contacts shows that the L8S8 hexadecamer is composed of four L2 dimers. The dominant contacts between these L2 dimers are formed by the small subunits. This suggests that the small subunits may be essential for maintaining the integrity of the L8S8 structure. The active site shows differences between the unactivated form and the quaternary complex. In particular, Lys334 has moved out of the active site by about 10A. This residue lies on loop 6 of the alpha beta barrel, which is a particularly mobile loop. The site of ribulose-1,5-bisphosphate carboxylase/oxygenase activation is well ordered in the absence of the carbamylation of Lys201 and Mg2+ binding. The residues are held poised by a network of hydrogen bonds. In the unactivated state, the active site is accessible to substrate binding. PMID- 1512239 TI - Binding of factor VIIIa and factor VIII to factor IXa on phospholipid vesicles. AB - The activation of factor X by factor IXa (fIXa) in the presence of phosphatidylcholine-phosphatidylserine (PCPS) vesicles is markedly accelerated by thrombin-activated factor VIII (fVIIIa). The interaction between highly purified fVIIIa and fIXa in this complex was studied fluorometrically at 25 degrees C by using a derivative of D-phenylalanyl-prolyl-arginyl-fIXa which was modified at the active site with fluorescein-5-maleimide (Fl-M-FPR-fIXa). Titration of Fl-M FPR-fIXa with fVIIIa at fixed PCPS resulted in a large, saturable increase in anisotropy (delta r = 0.09). The titration data were fit to a model assuming a reversible equilibrium between fVIIIa and fIXa, resulting in an apparent dissociation constant of 2 nM and a stoichiometry of 1 mol of fVIIIa/mol of Fl-M FPR-fIXa. The initial velocity of factor X activation was measured under identical conditions except that active fIXa and factor X were included, which yielded binding parameters similar to those determined fluorometrically. Thus, the fluorescence method accurately reflects complex formation between fVIIIa and fIXa on the phospholipid surface, and the fVIIIa-fIXa interaction is not influenced by the presence of the substrate, factor X. Addition of fVIII to Fl-M FPR-fIXa and PCPS produced a small, saturable increase in anisotropy (delta r = 0.03), followed by a larger increase (delta r = 0.07) upon addition of thrombin to activate fVIII. Thus, fVIII binds fIXa, but proteolytic modification of fVIII must occur before the complete fVIIIa-dependent structural change in the active site of fIXa, as reflected in the anisotropy change, occurs PMID- 1512240 TI - The active site of factor IXa is located far above the membrane surface and its conformation is altered upon association with factor VIIIa. A fluorescence study. AB - The topography of membrane-bound blood coagulation factor IXa (fIXa) and the nature of its interaction with its cofactor, factor VIIIa (fVIIIa), were examined using fluorescent derivatives of fIXa. A fluorescein dye was covalently attached to the active-site histidine of fIXa via a D-Phe-Pro-Arg tripeptide tether to form Fl-A-FPR-fIXa; similarly, a 5-dimethylaminonaphthalene-1-sulfonyl (dansyl) dye was covalently attached via Glu-Gly-Arg to form DEGR-fIXa. When either Fl-A FPR-fIXa or DEGR-fIXa was titrated with phosphatidylcholine-phosphatidylserine vesicles containing octadecylrhodamine in the presence of Ca2+, fluorescence energy transfer was observed. Assuming a random orientation of dyes, the distance of closest approach between the donor dyes in the active sites of the membrane bound enzymes and the acceptor dyes at the membrane surface was found to be 89 +/ 3 A for Fl-A-FPR-fIXa and 73 +/- 4 A for DEGR-fIXa. Although the exact distance remains uncertain, it is clear that the active site of fIXa is positioned more than 70 A above the surface, and hence that the elongated fIXa molecule projects approximately perpendicularly from the surface when bound to the membrane. The binding of fVIIIa to membrane-bound Fl-A-FPR-fIXa or DEGR-fIXa did not alter the location of the active site relative to the membrane surface, but did alter both the emission intensity and anisotropy of the fluorescein and dansyl probes and hence their environments. Cofactor stimulation of fIXa activity therefore appears to be mediated, at least in part, by a conformational change in the active site that occurs when fVIIIa binds to the enzyme on the phospholipid surface. PMID- 1512241 TI - Modulation of transcription of the platelet-derived growth factor A-chain gene by a promoter region sensitive to S1 nuclease. AB - Homodimers of the platelet-derived growth factor (PDGF) A-chain are strong mitogens for cells of mesenchymal origin. Differences in the levels of expression of the PDGF A-chain gene have been reported in both normal and transformed cell lines, suggesting that transcription of the PDGF A-chain gene is highly regulated. We have now identified two S1-hypersensitive sites which flank a 13 base pair oligo(dG).oligo(dC) sequence located 70-82 base pairs upstream of the transcription initiation site. Three lines of evidence suggest that these S1 sensitive sites contribute to optimum promoter activity. Nuclear protein(s) binding to these sites were detected in gel mobility shift assays. Deletion of the S1-sensitive sites results in a 2-3-fold decrease in the transcriptional activity and eliminated sensitivity to S1 nuclease. Deletions in the oligo(dG).oligo(dC) motif also eliminated sensitivity to S1 and resulted in a 2.5 fold decrease of the promoter activity in the stable transfection assays. The results suggest that the highly G+C-rich region in the PDGF A-chain gene promoter locally induces the formation of non-B-form DNA under torsional stress which appears to be important in the transcriptional regulation of the PDGF A-chain gene in vivo. PMID- 1512242 TI - Rhodopsin/transducin interactions. I. Characterization of the binding of the transducin-beta gamma subunit complex to rhodopsin using fluorescence spectroscopy. AB - In this work we have used fluorescence spectroscopic approaches to examine the binding of the beta gamma T subunit complex of transducin to the photoreceptor, rhodopsin. To do this, we have covalently labeled the beta gamma T subunit complex with the environmentally sensitive fluorescent cysteine reagent 2-(4' maleimidylanilino)naphthalene-6-sulfonic acid (MIANS). By using the MIANS moiety as a fluorescent reporter group, we were able to monitor directly the binding of the MIANS-beta gamma T complex to light-activated rhodopsin, which was reconstituted into phosphatidylcholine vesicles, through an enhancement (30-50%) in the MIANS fluorescence. Phosphatidylcholine vesicles, alone, elicited only minor changes in the MIANS-beta gamma T fluorescence (i.e. less than 10% enhancement), whereas the addition of rhodopsin in the absence of lipid vesicles and in minimal detergent fully mimicked the effects of reconstituted rhodopsin and caused a significant enhancement of the MIANS fluorescence. The interactions between the MIANS-beta gamma T complex and rhodopsin also resulted in a quenching of the rhodopsin tryptophan fluorescence (approximately 30%), which most likely reflected resonance energy transfer between the tryptophan residues and the MIANS moieties. The binding of the MIANS-beta gamma T species to the alpha T subunit was accompanied by an enhancement of the MIANS fluorescence (30-50%) and a slight blue shift of the emission maximum, as described previously (Phillips, W. J., and Cerione, R. A. (1991) J. Biol. Chem. 266, 11017-11024). However, the alpha T induced enhancement of the MIANS-beta gamma T fluorescence was not additive with the enhancement elicited by rhodopsin. Conditions which resulted in the activation of the alpha T subunit reversed the alpha T-induced enhancement of the MIANS emission, whereas the rhodopsin-induced enhancement persisted, thereby suggesting that the rhodopsin-beta gamma T complex can remain intact throughout the G protein activation event. Studies with synthetic peptides representing different regions of the cytoplasmic domain of rhodopsin demonstrated that a portion of the putative carboxyl-terminal tail (amino acid residues 310-324) was capable of eliciting changes in the MIANS-beta gamma T fluorescence as well as inhibiting the MIANS-beta gamma T-induced quenching of the rhodopsin tryptophan fluorescence. These results suggest that this region of the rhodopsin molecule may constitute a portion of the binding domain for the beta gamma T complex. PMID- 1512243 TI - Rhodopsin/transducin interactions. II. Influence of the transducin-beta gamma subunit complex on the coupling of the transducin-alpha subunit to rhodopsin. AB - In these studies we have investigated the role of the beta gamma T subunit complex in promoting the rhodopsin-stimulated guanine nucleotide exchange reaction (i.e. the activation event) of the alpha T subunit. The results of these studies demonstrate that although the beta gamma T subunit complex increases the association of the alpha T subunit with lipid vesicles that lack the photoreceptor, the beta gamma T complex is not necessary for the binding of alpha T to lipid vesicles containing rhodopsin, provided sufficient amounts of rhodopsin are present. The rhodopsin-promoted GDP/guanosine 5'-O-(3 thiotriphosphate) (GTP gamma S) exchange reaction, within the rhodopsin-alpha T complex, then results in the dissociation of the alpha TGTP gamma S species from the rhodopsin-containing phospholipid vesicles. A second line of evidence for the occurrence of rhodopsin/alpha T interactions, in the absence of beta gamma T, comes from phosphorylation studies using the beta 1 isoform of protein kinase C. The phosphorylation of the alpha T subunit by protein kinase C is inhibited by beta gamma T, both in the absence and in the presence of rhodopsin, but is enhanced by rhodopsin in the absence of beta gamma T. These rhodopsin-alpha T complexes also appear to be capable of undergoing a rhodopsin-stimulated guanine nucleotide exchange event. When the guanine nucleotide exchange is allowed to occur prior to the addition of protein kinase C, the phosphorylation of the alpha T subunit is inhibited. Although beta gamma T is not absolutely required for the rhodopsin/alpha T interaction, it appears to increase the apparent affinity of the alpha T subunit for rhodopsin, both when rhodopsin was inserted into phosphatidylcholine vesicles and when soluble lipid-free preparations of rhodopsin were used. This results in a significant kinetic advantage for the rhodopsin-stimulated guanine nucleotide exchange event, such that the addition of beta gamma T causes a 10-fold promotion of the rhodopsin-stimulation [35S]GTP gamma S binding to alpha T after 1 min but provides less than a 20% promotion of the rhodopsin-stimulated binding after 1 h. The ability of beta gamma T to increase the association of alpha T with the lipid vesicle surface does not appear to contribute significantly to the ability of rhodopsin to couple functionally to alpha T subunits, and there appears to be no requirement for beta gamma T in the alpha T activation event, once the rhodopsin-alpha T complex has formed. PMID- 1512244 TI - Protein sequence and mass spectrometric analyses of tau in the Alzheimer's disease brain. AB - Tau with unusually slow mobilities in sodium dodecyl sulfate-polyacrylamide gel electrophoresis was purified from the Sarkosyl-insoluble pellet of Alzheimer's disease brain homogenates. Such species of tau (PHF-tau) are considered to construct the framework of the sodium dodecyl sulfate-soluble form of paired helical filaments (PHF). Detailed comparison of peptide maps of PHF-tau and normal tau before and after dephosphorylation pointed to three anomalously eluted peaks which contained abnormally phosphorylated peptides, residues 191-225, 226 240, 260-267, and 386-438, according to the numbering of the longest tau isoform (Goedert, M., Spillantini, M. G., Jakes, R., Rutherford, D., and Crowther, R. A. (1989) Neuron 3, 519-526). Protein sequence and mass spectrometric analyses localized Thr-231 and Ser-235 as the abnormal phosphorylation sites and further indicated that each tau 1 site (residues 191-225) and the most carboxyl-terminal portion of the protein (residues 386-438) carries more than two abnormal phosphates. Ser-262 was also phosphorylated in a fraction of PHF-tau. Modifications other than phosphorylation, removal of the initiator methionine, and N alpha-acetylation at the amino terminus and deamidation at 2 asparaginyl residues were found in PHF-tau, but these modifications were also present in normal tau. PMID- 1512245 TI - The catalytic site residues and interfacial binding of human pancreatic lipase. AB - In this study, the essential serine residue and 2 other amino acids in human pancreatic triglyceride lipase (triacylglycerol acylhydrolase, EC 3.1.1.3) were tested for their contribution to the enzyme's catalytic site or interfacial binding site. By site-specific mutagenesis of the cDNA for human pancreatic lipase, amino acid substitutions were made at Ser153, His264, and Asp177. The mutant cDNAs were expressed in transfected COS-1 cells. Both the medium and the cells were examined for the presence of pancreatic lipase by Western blot analysis. The activity of the expressed proteins against triolein and the interfacial binding was measured. Proteins with mutations in Ser153 were secreted by the cells and bound to interfaces but had no detectable activity. Changing His264 to a leucine or Asp177 to an asparagine also produced inactive lipase. Substituting glutamic acid for Asp177 produced an active protein. These results demonstrate that Ser153 is involved in the catalytic site of pancreatic lipase and is not crucial for interfacial binding. Moreover, the essential roles of His264 and Asp177 in catalysis were demonstrated. A Ser-His-Asp catalytic triad similar to that present in serine proteases is present in human pancreatic lipase. PMID- 1512246 TI - Mass spectrometry of purified amyloid beta protein in Alzheimer's disease. AB - The amyloid beta-protein (A beta) that is progressively deposited in Alzheimer's disease (AD) arises from proteolysis of the integral membrane protein, beta amyloid precursor protein (beta APP). Although A beta formation appears to play a seminal role in AD, only a few studies have examined the chemical structure of A beta purified from brain, and there are discrepancies among the findings. We describe a new method for the rapid extraction and purification of A beta that minimizes artifactual proteolysis. A beta purified by two-dimensional reverse phase HPLC was analyzed by combined amino acid sequencing and mass spectrometry after digestion with a lysylendopeptidase. The major A beta peptide in the cerebral cortex of all five AD brains examined was aspartic acid 1 to valine 40. A minor species beginning at glutamic acid 3 but blocked by conversion to pyroglutamate was also found in all cases. A species ending at threonine 43 was detected, varying from approximately 5 to 25% of total A beta COOH-terminal fragments. Peptides ending with valine 39, isoleucine 41, or alanine 42 were not detected, except for one brain with a minor peptide ending at valine 39. Our findings suggest that A beta 1-40 is the major species of beta-protein in AD cerebral cortex. A beta 1-40 and A beta 1-43 peptides could arise independently from beta APP, or A beta 1-43 could be the initial excised fragment, followed by digestion to yield A beta 1-40. These analyses of native A beta in AD brain recommend the use of synthetic A beta 1-40 peptide to model amyloid fibrillogenesis and toxicity in vitro. PMID- 1512247 TI - Photoaffinity labeling of fatty acid-binding proteins involved in long chain fatty acid transport in Escherichia coli. AB - The photoreactive fatty acid 11-m-diazirinophenoxy-[11-3H]undecanoate was shown to be taken up specifically by the fatty acid transport system expressed in Escherichia coli grown on oleate. This photoreactive fatty acid analogue was therefore used to identify proteins involved in fatty acid uptake in E. coli. The fadL protein was labeled by the probe, confirmed to be exclusively in the outer membrane and to exhibit the heat modifiable behavior typical of outer membrane proteins. The apparent pI of the incompletely denatured form of the protein having the mobility of a 33-kDa protein was 4.6 while that of the fully denatured form was consistent with the calculated value of 5.2. The denaturation was reversible depending upon the protein to detergent ratios. The photoreactive fatty acid partitions into the outer membrane, resulting in extensive photolabeling of the lipid; a high affinity fatty acid-binding site is not apparent in total membranes labeled using free fatty acids due to this large binding capacity of the outer membrane. However, when the free fatty acid concentration was controlled by supplying it as a bovine serum albumin complex, the fadL protein exhibited saturable high affinity fatty acid binding, having an apparent Kd for the probe of 63 nM. The methods described very readily identify fatty acid-binding proteins: the fact that even when the sensitivity was increased 500-fold, no evidence was found for the presence of a fatty acid binding protein in the inner membrane is consistent with the proposal that fatty acid permeation across the plasma membrane is not protein mediated but occurs by a simple diffusive mechanism. PMID- 1512248 TI - Purification and characterization of dihydropyrimidine dehydrogenase from human liver. AB - Although dihydropyrimidine dehydrogenase has been purified to varying degrees from several species, very little is known about the human enzyme. The importance of this enzyme has recently been shown with cancer chemotherapy, particularly in patients with genetic deficiency of this enzyme. In the present study, this enzyme was purified 7800-fold to homogeneity from human liver by introducing several novel methods including chromatofocusing, HPLC gel filtration, reversed phase HPLC for the enzyme assay. Purified human enzyme has a molecular mass of 210 +/- 5 kDa and appears to be composed of two subunits. The apparent pI is pH 4.6 (+/- 0.2). The human enzyme contains approximately four flavin nucleotide molecules (two each of FAD and FMN) and 33 iron atoms per molecule of enzyme. Kinetic studies with uracil, thymine, 5-fluorouracil, and NADPH were carried out. Amino acid composition and the N-terminal amino acid sequence of this enzyme were reported. A rabbit polyclonal antibody was raised and shown to be specific for the human liver enzyme. In conclusion, in the present manuscript, we report not only a novel procedure for purification of dihydropyrimidine dehydrogenase from human liver but also new data on its properties compared to other species, which will provide a basis for further biochemical and molecular studies of this enzyme. PMID- 1512249 TI - Transforming growth factor-beta inhibits phosphorylation of the retinoblastoma susceptibility gene product in human monocytic leukemia cell line JOSK-I. AB - Proliferation of the human monocytic leukemia cell line JOSK-I is inhibited by transforming growth factor-beta (TGF-beta). Growth inhibition by TGF-beta was not due to either a toxic effect or to induction of differentiation. TGF-beta induced a cell cycle arrest at late G1 phase and was not found to be inhibitory to JOSK-I cells in S phase or G2/M. This G1 cell cycle arrest was associated with an accumulation of the unphosphorylated form of the retinoblastoma susceptibility gene product (Rb) in good correlation with inhibition of DNA synthesis. In contrast to the effects of TGF-beta, two other agents which induced a G1 arrest of JOSK-I cells had a different effect on Rb. Aphidicolin blocked cells at G1/S but could not reduce Rb phosphorylation as great as that seen with TGF-beta. 12-O Tetradecanoylphorbol-13-acetate, an inducer of differentiation, did reduce Rb phosphorylation, but not until 72 h, when differentiation had already occurred. The identities of the Rb kinases are unknown, but recent evidence suggests that the cdc2 gene product could participate in Rb phosphorylation. Although cdc2 mRNA and total protein levels were not affected, TGF-beta inhibited the rate of translation and kinase activity of cdc2 in JOSK-I cells. These results suggest that growth inhibition of hematopoietic cells by TGF-beta is linked to suppression of Rb phosphorylation to retain Rb in an unphosphorylated, growth inhibitory state. The suppression of Rb phosphorylation is suggested to be mediated through inhibition of cdc2 kinase activity by TGF-beta. PMID- 1512250 TI - Plasminogen activator inhibitor-1 binds to fibrin and inhibits tissue-type plasminogen activator-mediated fibrin dissolution. AB - Plasminogen activator inhibitor-1 (PAI-1) accumulates within thrombi and forming whole blood clots. To explore this phenomenon at the molecular level, PAI-1 binding to fibrin was examined. The experiments were performed by adding 125I-PAI 1, which retains its complete tissue-type plasminogen (t-PA) inhibitory activity, to fibrin matrices formed in 2-cm2 tissue culture wells. Guanidine HCl-activated PAI-1 binding was reversible and was inhibited in the presence of excess, unlabeled PAI-1. Activated 125I-PAI-1 recognized 2 sites on fibrin: a very small number of high affinity sites (Kd less than 1 nM) and principally a large number of low affinity sites with an approximate Kd of 3.8 microM. Latent PAI-1 bound to fibrin at a site indistinguishable from the lower affinity site recognized by activated PAI-1. Fibrin, pretreated with activated PAI-1, was protected from t-PA mediated plasmin degradation in a PAI-1 dose-responsive manner (IC50 = 12.3 nM). Clot protection correlated with partial occupancy of the low affinity PAI-1 binding site on fibrin and was due to the formation of sodium dodecyl sulfate stable, PAI-1.t-PA complexes. Latent PAI-1 (27 nM) did not protect the fibrin from dissolution. The localization of PAI-1 to a thrombus by virtue of its fibrin binding potential could result in significant protection of the thrombus from the degradative effects of the fibrinolytic system. PMID- 1512251 TI - Calvasculin, an encoded protein from mRNA termed pEL-98, 18A2, 42A, or p9Ka, is secreted by smooth muscle cells in culture and exhibits Ca(2+)-dependent binding to 36-kDa microfibril-associated glycoprotein. AB - Calvasculin, an EF-hand protein with a molecular mass of 11 kDa on sodium dodecyl sulfate-polyacrylamide gel electrophoresis, is present abundantly in bovine aorta (Watanabe, Y., Kobayashi, R., Ishikawa, T., and Hidaka, H. (1992) Arch. Biochem. Biophys. 292, 563-569). This protein is synthesized constitutively by bovine aortic smooth muscle (BASM) cells and rat embryo fibroblast 3Y1 cells in culture. We discovered that calvasculin was secreted by BASM cells and 3Y1 cells. Immunofluorescence staining of BASM cells showed a granular distribution for calvasculin that was typical of a secreted protein. This protein bound with an extracellular matrix protein, 36-kDa microfibril-associated glycoprotein (36-kDa MAP), in a Ca(2+)-dependent manner in vitro. A stoichiometry analysis showed that the 36-kDa MAP bound 2.2 calvasculin eq/mol of protein. Solid-phase binding assays indicated a preferential affinity of native calvasculin for 36-kDa MAP among the extracellular matrices in a Ca(2+)-dependent manner. These results suggest that calvasculin, intracellular Ca(2+)-binding protein, is released to the extracellular space and binds with 36-kDa MAP. PMID- 1512252 TI - Overexpression and rapid purification of the orfE/rph gene product, RNase PH of Escherichia coli. AB - The pyrE gene, encoding the pyrimidine biosynthetic enzyme orotate phosphoribosyltransferase, is the promoter distal gene of the dicistronic orfE pyrE operon. The promoter proximal orfE gene, whose transcription and translation is important for regulation of the pyrE attenuator, encodes a 238-amino acid residue protein which was recently identified as the phosphorolytic ribonuclease, RNase PH, that removes nucleotides from the 3' ends of tRNA precursors. In this paper we report the construction of a plasmid, which overexpresses the orfE and pyrE gene products substantially, as well as the purification of the OrfE protein by ammonium sulfate precipitation and chromatography on phosphocellulose. The highly purified protein catalyzes the phosphorolytic cleavage of poly(A) at a rate of 1.6 mumol/min/mg and the formation of CDP from tRNA-CCA-Cn and orthophosphate at a rate equal to 0.14 mumol/min/mg, as characteristic for RNase PH. OrfE/RNase PH contains helix-turn-helix motifs resembling those in DNA binding proteins, and it binds nonspecifically to DNA. On SDS gels, OrfE/RNase PH migrates as two distinct protein bands. This heterogeneity might be caused by post-translational modification other than proteolysis, or may be an electrophoretic artifact. The native protein is composed of two or more subunits. PMID- 1512253 TI - Characterization of Escherichia coli RNase PH. AB - We have previously shown that the orfE gene of Escherichia coli encodes RNase PH. Here we show that the OrfE protein (purified as described in the accompanying paper) (Jensen, K. F., Andersen, J. T., and Poulsen, P. (1992) J. Biol. Chem. 267, 17147-17152) has both the degradative and synthetic activities of RNase PH. This highly purified protein was used to characterize the enzymatic and structural properties of RNase PH. The enzyme requires a divalent cation and phosphate for activity, the latter property indicating that RNase PH is exclusively a phosphorolytic enzyme. Among tRNA-type substrates, the enzyme is most active against synthetic tRNA precursors containing extra residues following the -CCA sequence, and it can act on these molecules to generate mature tRNA with amino acid acceptor activity; 3'-phosphoryl-terminated molecules are not active as substrates. The equilibrium constant for RNase PH is near unity, suggesting that at the phosphate concentration present in vivo, the enzyme would participate in RNA degradation. The synthetic reaction of RNase PH displays a nonlinear response to increasing enzyme concentrations, and this may be due to self aggregation of the protein. Higher order multimers of RNase PH could be detected by gel filtration at higher protein concentrations and by protein cross-linking. The possible role of RNase PH in tRNA processing is discussed. PMID- 1512254 TI - 4-oxatetradecanoic acid is fungicidal for Cryptococcus neoformans and inhibits replication of human immunodeficiency virus I. AB - Candida albicans and Cryptococcus neoformans are major causes of systemic fungal infections, particularly in patients with acquired immunodeficiency syndrome. Metabolic labeling studies revealed that these organisms synthesize a small number of N-myristoylproteins, the most prominent being 20-kDa ADP-ribosylation factors (Arfs). C. albicans Arf has approximately 80% identity with the essential Arf1 and Arf2 proteins of Saccharomyces cerevisiae. [3H]Myristic acid analogs with oxygen for -CH2- substitutions at C4, C6, C11, and C13 are incorporated into cellular N-myristoylproteins, phospholipids, and neutral lipids produced by these three yeasts during exponential growth at 30 degrees C in complex media. Analog- and organism-specific differences in the efficiency of labeling of proteins and lipid classes were observed. The effects of oxatetradecanoic acids with oxygen for -CH2- substitutions at C3-C13 on C. neoformans, C. albicans, and S. cerevisiae were assessed during mid-log phase growth at 30 degrees C. A single dose of 3-oxa-, 4-oxa-, 5-oxa- or 6-oxatetradecanoic acid (O3-O6, final concentration = 300 microM) was able to inhibit growth of C. neoformans in the order O4 greater than O5 greater than O3 approximately O6. The other compounds were inactive. 4-Oxatetradecanoic acid was fungicidal, producing a 10,000-fold reduction in viable cell number 1 h after administration and continued suppression of cell growth for 7 h. A clear dose response was observed over a concentration range of 100-300 microM. 4-Oxatridecanoic acid was 100-fold less potent in reducing cell viability than 4-oxatetradecanoic acid but more potent than 5-oxatridecanoic acid. O4 produced approximately 10-100-fold reductions in the viability of C. albicans and S. cerevisiae at 300-500 microM, respectively, whereas O5 and O6 were less active. Since N-myristoylation of the Pr55gag polyprotein precursor produced by human immunodeficiency virus I (HIV-I) is essential for its assembly, we also assessed the antiviral effects of 4 oxatetradecanoic acid. O4 is able to produce a 50% reduction in the replication of HIV-I in acutely infected human T-lymphocyte cell lines at a concentration of 18 microM. Together, these data suggest that (i) the position of the oxygen for methylene substitution is a critical determinant of the fungicidal activity of O4 and (ii) NMT may be an attractive therapeutic target for treating opportunistic fungal infections in patients infected with HIV-I. PMID- 1512255 TI - Insect proteins homologous to mammalian high mobility group protein 1. Characterization and DNA-binding properties. AB - Two chromosomal high mobility group (HMG) proteins from larvae of Chironomus thummi (Diptera) and from an epithelial cell line of Chironomus tentans were purified to homogeneity and chemically characterized. cDNA clones encoding these proteins were isolated from an expression library using an immunoscreening approach and were sequenced. The deduced amino acid sequences revealed their homology to HMG protein 1 of vertebrates. These insect proteins have therefore been designated cHMG1a and cHMG1b. They have a molecular mass of 12,915 and 12,019 kDa, respectively, and preferentially bind to AT-rich DNA. Indirect immunofluorescence microscopy with a polyclonal antibody showed the presence of cHMG1a and cHMG1b in condensed chromomeres but not in puffs, nucleoli, and cytoplasm. The cHMG1a and cHMG1b genes were both localized to a single band in region 14 of chromosome 1 of C. tentans and appear to be single copy genes. An immunologically related protein was purified from Drosophila melanogaster Kc cells. Its size and amino acid composition indicate that it is an HMG1 of D. melanogaster. On the other hand, our antibody did not recognize calf HMG1. The identification and characterization of HMG1 proteins in insects with polytene chromosomes opens new possibilities for studying function(s) of this group of chromosomal proteins. PMID- 1512256 TI - Functional characterization of protease-treated Bacillus anthracis protective antigen. AB - Characterization of the functional domains of Bacillus anthracis protective antigen (PA, 83-kDa), the common cellular binding molecule for both anthrax edema toxin and anthrax lethal toxin, is important for understanding the mechanism of entry and action of the anthrax toxins. In this study, we generated both biologically active (facilitates killing of J774A.1 cells in combination with lethal factor, LF) and inactive preparations of PA by protease treatment. Limited proteolytic digestion of PA in vitro with trypsin generated a 20-kDa fragment and a biologically active 63-kDa fragment. In contrast, limited digestion of PA with chymotrypsin yielded a preparation containing 37- and 47-kDa fragments defective for biological activity. Treatment with both chymotrypsin and trypsin generated three major fragments, 20, "17," and 47 kDa as determined by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. This PA preparation was also biologically inactive. To investigate the nature of the defect resulting from chymotrypsin treatment, we assayed PA preparations for the ability to bind to the cellular receptor and to bind and internalize 125I-LF. All radiolabeled PA preparations bound with specificity to J774A.1 cells and exhibited affinities similar to native 83-kDa PA. Once bound to the cell surface receptor, both trypsin-treated PA and chymotrypsin/trypsin-treated PA specifically bound 125I-LF with high affinity. Finally, these PA preparations delivered 125I-LF to a Pronase resistant cellular compartment in a time- and temperature-dependent fashion. Thus, the biological defect exhibited by chymotrypsin-treated PA is not at the level of cell binding or internalization but at a step later, such as toxin routing or processing by J774A.1 cells. These protease-treated preparations of PA should prove useful in both elucidating the intracellular processing of anthrax lethal toxin and determining the structure-function relationship of PA and LF. PMID- 1512257 TI - Activated Src tyrosine kinase phosphorylates Tyr-457 of bovine GTPase-activating protein (GAP) in vitro and the corresponding residue of rat GAP in vivo. AB - GTPase-activating protein (GAP) is a key regulator of the cellular Ras protein, which is implicated in oncogenic signal transduction pathways downstream of the viral Src (v-Src) kinase. Previous studies demonstrated that v-Src induces tyrosine phosphorylation of GAP, suggesting that GAP may provide a biochemical link between v-Src and Ras signaling pathways. To determine the precise residues in GAP phosphorylated by Src kinases, we used a baculovirus/insect cell expression system for investigating in vitro phosphorylation of GAP. Phosphopeptide mapping analysis revealed that v-Src and normal cellular Src (c Src) phosphorylate tyrosine residues in bovine GAP at one major site and one minor site in vitro. Significantly, the major site of GAP phosphorylation in vitro is also the major site of in vivo tyrosine phosphorylation of GAP in rat fibroblasts transformed by v-Src. Analyses of GAP deletion mutants and TrpE-GAP fusion proteins established that Tyr-457 of bovine GAP (and the corresponding residue of rat and human GAP) is the major site of tyrosine phosphorylation. Our results demonstrate that the v-Src kinase induces phosphorylation of the same tyrosine residue of GAP in vitro and in vivo, suggesting that GAP is a direct substrate of activated Src kinases in vivo. Because epidermal growth factor receptor phosphorylates the equivalent tyrosine residue in human GAP (Tyr-460), these findings are consistent with the hypothesis that specific phosphorylation of GAP at this site may have a physiologically important role in regulating mitogenic Ras signaling pathways. PMID- 1512258 TI - Cloning and structural analysis of the gene for the regulatory subunit of cAMP dependent protein kinase in Blastocladiella emersonii. AB - We have isolated and characterized cDNA and genomic DNA clones encoding the regulatory subunit of cAMP-dependent protein kinase in the aquatic fungus Blastocladiella emersonii. Nucleotide sequence analysis has shown that the predicted protein comprises 403 amino acids with a calculated molecular mass of 44,263 Da and an overall 40% identity to mammalian RII subunits, including a serine in the phosphorylation site, which confirms the Blastocladiella protein as a type II regulatory subunit. The B. emersonii R gene presents two introns, one located in the 5'-noncoding region, whereas the other interrupts the coding region, just after the dimerization domain of the protein. The promoter region does not contain recognizable TATA or CCAAT sequences and is very GC rich, a characteristic shared by mammalian cAMP-dependent protein kinase subunit genes previously analyzed. S1 mapping and primer extension experiments revealed multiple transcription initiation sites. Several sequence motifs were identified in the 5'-flanking region which could be responsible for the regulation of this gene. PMID- 1512259 TI - Cloning and functional expression of Dfurin2, a subtilisin-like proprotein processing enzyme of Drosophila melanogaster with multiple repeats of a cysteine motif. AB - Production of a variety of regulatory eukaryotic proteins, such as growth factors and polypeptide hormones, often involves endoproteolytic processing of proproteins at cleavage sites consisting of paired basic residues. The first known mammalian proprotein processing enzyme with such specificity is the human fur gene product furin. Structurally and functionally, furin is related to the subtilisin-like serine endoprotease kexin (EC 3.4.21.61) of yeast Saccharomyces cerevisiae; unlike kexin, it contains a cysteine-rich region with an unknown function. Here, we describe cloning and sequencing of a 5.8-kbp cDNA of the Dfur2 gene, a fur-like gene of Drosophila melanogaster, which we found expressed during various stages of development. This Dfur2 cDNA has an open reading frame for a 1680-residue protein, called Dfurin2. Dfurin2 contains similar protein domains as mammalian furin, however, it has an extended amino-terminal region and its cysteine-rich region is much larger than that of mammalian furin. Because of this latter phenomenon, we were able to identify a particular cysteine motif that was repeated multiple times in Dfurin2 but present only twice in mammalian furin. Furthermore, we show that Dfur2 encodes an endoproteolytic enzyme with specificity for paired basic amino acid residues as, in cotransfection experiments, correct cleavage was demonstrated of the precursor of the von Willebrand factor but not of a cleavage mutant. Finally, Dfur2 was mapped to region 14C of the X chromosome of D. melanogaster. PMID- 1512260 TI - Two gap junction genes, connexin 31.1 and 30.3, are closely linked on mouse chromosome 4 and preferentially expressed in skin. AB - Two new gap junction genes isolated from the mouse genome code for connexin homologues of 271 and 266 amino acids, designated here Cx31.1 and Cx30.3, respectively. The two open reading frames, oriented in the same direction, are only 3.4 kb apart on mouse chromosome 4. Within the connexin family, these two proteins are most closely related to one another (70% amino acid sequence identity) and to Cx31 (65 and 68% identity, respectively). Comparison of the Cx31.1 mouse gene with a Cx31.1 cDNA showed a similar genomic organization to that found with other members of the connexin gene family, i.e. the coding and 3' untranslated regions are contained within a single exon, which is preceded by an intron, less than 25 bases upstream of the ATG start codon. Northern blot hybridization revealed highly tissue-specific coexpression of the 1.6-kb Cx31.1 mRNA and two Cx30.3 transcripts of 1.9- and 3.2-kb size, predominantly in skin and two related mouse keratinocyte cell lines. Minor levels of Cx31.1 mRNA were detected in testis. Microinjection of Cx30.3, but not Cx31.1 cRNA, into Xenopus oocyte pairs induced formation of functional gap junction channels with unique voltage-gated parameters compared to other connexins expressed similarly. PMID- 1512261 TI - Expression and function of GLUT-1 and GLUT-2 glucose transporter isoforms in cells of cultured rat pancreatic islets. AB - We have previously investigated glucose induction of glucokinase, glucose usage and insulin release in isolated cultured rat pancreatic islets (Liang, Y., Najafit, H., Smith, R. M., Zimmerman, E. C., Magnuson, M. A., Tal, M., and Mastchinsky, F. M. (1992) Diabetes (1992) 41, 792-806). Here we studied the expression and function of GLUT-1 and GLUT-2 glucose transporter isoforms, using the same system, i.e. isolated pancreatic rat islets immediately after isolation or cultured in the presence of 3 or 30 mM glucose for as long as 10 days. We found by immunofluorescence microscopy and Western and Northern blot analysis of islet extracts that GLUT-1 expression was induced in islet beta-cells in tissue culture both with low or high glucose present. The induction of GLUT-1 was specific to beta-cells but was not present in all beta-cells and was not detected in alpha-cells. GLUT-2 expression was also specific for beta-cells and was not observed in all beta-cells. Some beta-cells in culture coexpressed GLUT-1 and GLUT-2. The expression of the two glucose transporters was regulated in the opposite direction in response to glucose concentration in the culture medium. GLUT-1 was more effectively induced when glucose was low, and GLUT-2 expression was more pronounced when glucose was high in the culture media. Another difference between the two glucose transporters was that GLUT-2 expression was increased while GLUT-1 expression was decreased as culturing continued as long as 7 days. Thus, after 7 days of culture GLUT-2 expression in beta-cells was nearly the same at low and high glucose, whereas GLUT-1 was practically absent no matter what the glucose level was. In attempts to correlate GLUT-1 and GLUT-2 expression to beta-cell function glucose uptake and glucose-stimulated insulin release in fresh and cultured islets were measured. In freshly isolated islet glucose uptake was estimated to be 100-fold in excess of actual glucose use. Glucose uptake was reduced by 7-day culture to about one-third of that observed in freshly isolated islets no matter what the glucose concentration of the culture media. We conclude that in the present experimental system GLUT-1 and GLUT-2 expression and function are not closely associated with glucose usage rates or the secretory function of beta-cells. PMID- 1512262 TI - A third quaternary structure of human hemoglobin A at 1.7-A resolution. AB - Previous crystallographic studies have shown that human hemoglobin A can adopt two stable quaternary structures, one for deoxyhemoglobin (the T-state) and one for liganded hemoglobin (the R-state). In this paper we report our finding of a second quaternary structure (the R2-state) for liganded hemoglobin A. The magnitudes of the spatial differences between the R- and R2-states are as large as those between the R- and T-states. Of particular interest are the structural changes that occur as a result of R-T and R-R2 transitions at the so-called "switch" region of the critical alpha 1 beta 2 interface. In the R-state, His-97 beta 2 is positioned between Thr-38 alpha 1 and Thr-41 alpha 1, whereas in transition to the T-state His 97 beta 2 must "jump" a turn in the alpha 1 C helix to form nonpolar contacts with Thr-41 alpha 1 and Pro-44 alpha 1. This facet of the R-T transition presents a major steric barrier to the quaternary structure change. In the R2-state, His-97 beta 2 simply rotates away from threonines 38 alpha 1 and 41 alpha 1, breaking contact with these residues and allowing water access to the center of the alpha 1 beta 2 interface. With the switch region in an open position in the R2-state, His-97 beta 2 should be able to move by Thr-41 alpha 1 and make the transition to the T-state with a steric barrier that is less than that for the R-T transition. Thus the R2-state may function as a stable intermediate along a R-R2-T pathway. The T-, R-, and R2-states must coexist in solution. That is, the fact that these states can be crystallized implies that they are all energetically accessible structures. What remains to be determined are the T-to-R, T-to-R2, and R-to-R2 equilibrium constants for hemoglobin under various solution conditions and ligation states. Although this may prove to be difficult, we discuss previously published results which indicate that low concentrations of inorganic anions or low pH may favor the R2-state and at least one alpha 1 beta 2 interface mutation stabilizes a quaternary structure that is very similar to the R2-state. PMID- 1512263 TI - Enzymic activities of two-chain pepsinogen, two-chain pepsin, and the amino terminal lobe of pepsinogen. AB - In order to study the relationships of aspartic proteases, we have modified pepsin, a single-chain eukaryotic enzyme, to a two-chain heterodimer, which resembles aspartic proteases from retrovirus, including human immunodeficiency virus. Two fragments of pepsinogen, residues 1P-172 and 173-326, were expressed separately in Escherichia coli. Mixtures of chains were refolded from urea solutions to generate an active two-chain pepsinogen, which was converted to two chain pepsin in acid solutions. The intramolecular and bimolecular activation constants (k1 and k2) of two-chain pepsinogen are about 1.5-fold and one-sixth, respectively, of those for pepsinogen. Structural evidence suggests that the faster k1 of two-chain pepsinogen is due to decreased interaction of the propeptide with the pepsin moiety, implying that the rate-limiting step in the intramolecular activation of pepsinogen is the "conformational dissociation" of its propeptide. Two-chain pepsin has the same Km but only one-sixth of the kcat of pepsin. Both pepsinogen chains are capable of independent refolding. The refolding of the NH2-terminal chain, which contains the propeptide and the NH2 terminal lobe, generated a small amount of proteolytic activity which is likely derived from the homodimer of the NH2-terminal lobe. It has been postulated that mammalian aspartic proteases, which contain two structurally homologous lobes, are derived in evolution from a homodimer enzyme by gene duplication and fusion (Tang, J., James, M. N. G., Hsu, I.-N., Jenkins, J. A., and Blundell, T. L. (1978) Nature 271, 618-621). The observation of the homodimer activity of the NH2 terminal lobe of pepsinogen suggests that the interface of the lobes is conservative in evolution. PMID- 1512264 TI - Cell adhesion in a dynamic flow system as compared to static system. Glycosphingolipid-glycosphingolipid interaction in the dynamic system predominates over lectin- or integrin-based mechanisms in adhesion of B16 melanoma cells to non-activated endothelial cells. AB - Initial adhesion of B16 melanoma variants to non-activated endothelial cells is mediated through specific interaction between GM3 (NeuAc alpha 2----3Gal beta 1-- -4Glc beta 1----Cer) expressed on melanoma cells and lactosylceramide (LacCer, Gal beta 1----4Glc beta 1----Cer) expressed on endothelial cells. This adhesion is predominant over integrin- or lectin-mediated adhesion in a dynamic flow experimental system employing a parallel plate laminar flow chamber (Lawrence, M. B., Smith, C. W., Eskin, S. G., and McIntire, L. V. (1990) Blood 75, 227-237). In this system, a tumor cell suspension flows over a glass plate coated with glycosphingolipid, lectin, or fibronectin, and adhesion is recorded on videotape. These conditions were designed to mimic the microvascular environment in which tumor metastatic deposition takes place. In contrast, lectin- and fibronectin based mechanisms are predominant in previously used static adhesion systems. Under static conditions, the relative degree of adhesion of the four B16 variants to endothelial cells or to LacCer-coated plates was the same as their relative degree of GM3 expression (i.e. BL6 approximately F10 greater than F1 greater than WA4), and adhesion was inhibited in the presence of methyl-beta-lactoside, or liposomes containing LacCer or GM3. Adhesion was also inhibited by pretreatment of B16 cells with anti-GM3 antibody DH2 or sialidase and by pretreatment of endothelial cells with anti-LacCer antibody T5A7. Under dynamic flow conditions, WA4 cells did not adhere to mouse endothelial cells at high shear stress (greater than 2.5 dynes/cm2) but did adhere at lower shear stress. In contrast, BL6 and F10 cells adhered strongly at both low and high shear stress. BL6 cell adhesion to endothelial cells at both low and high shear stress was inhibited in the presence of antibody DH2, ethyl-beta-lactoside, or lactose, as well as by pretreatment of BL6 cells with sialidase. Thus, some clear differences, as well as similarities, in cell adhesion under static versus dynamic conditions are demonstrated. These findings suggest that melanoma cell adhesion to endothelial cells, based on GM3/LacCer interaction, initiates metastatic deposition, which may trigger a series of "cascade" reactions leading to activation of endothelial cells and expression of Ig family or selectin receptors, thereby promoting adhesion and migration of tumor cells. PMID- 1512265 TI - Coordinated expression of phosphorylase kinase subunits in regenerating skeletal muscle. AB - The developmental expression of the alpha, beta, and gamma subunits of skeletal muscle phosphorylase kinase has been examined in regenerating muscle. Rat extensor digitorum longus (EDL) muscles, treated with bupivacaine, promptly undergo a rapid degeneration of the muscle, followed by regeneration and recovery of essentially normal morphology and physiology by 3-4 weeks post-treatment (Hall Craggs, E. C. B., and Seyan, H. S. (1975) Exp. Neurol. 46, 345-354). Phosphorylase kinase activity dropped to approximately 10% of control within 3 days of bupivacaine treatment and remained at this low level for several days but had attained at least 60% of normal levels by day 21. The pH 6.8/8.2 activity ratio was unusually high during the period of low activity, suggesting that the catalytic activity was not under normal regulation at this time. The subunit mRNAs were readily detected in control EDL but were undetectable at day 3 post bupivacaine treatment. Very small amounts of message for all three subunits were evident by day 6 and began to approach normal levels by day 12-15. The mRNA for both the alpha and alpha' subunits of phosphorylase kinase exhibited a similar pattern of recovery, as did also the mRNA for phosphorylase. In contrast to both phosphorylase kinase and phosphorylase, actin mRNA exhibited a quite a different pattern, with a nearly full recovery of message levels by day 6 post-bupivacaine. These data indicate that synthesis of phosphorylase and the alpha, beta, and gamma subunits of phosphorylase kinase appears to be coordinately regulated at the level of message accumulation and that the expression of phosphorylase kinase activity is likely to be also regulated post-transcriptionally. PMID- 1512266 TI - Identification of the alpha IIb beta 3 integrin in murine tumor cells. AB - Previously, we have identified an alpha IIb beta 3-like integrin in tumor cells by using antibodies against platelet alpha IIb beta 3. However, alpha IIb beta 3 was considered to be expressed strictly in megakaryocyte lineage cells. In order to resolve this controversy, the alpha IIb beta 3-like integrin in murine B16 amelanotic melanoma (B16a) cells was characterized at DNA, RNA, and protein levels. The presence of alpha 5, alpha v, alpha IIb, beta 1, and beta 3 genes in B16a cells was confirmed by Southern analysis. mRNAs for all these integrins except alpha v were detectable by Northern blotting. The alpha IIb beta 3 protein was identified by Western blotting using subunit-specific antibodies and by immunoprecipitation using complex-specific antibody. The alpha IIb beta 3 integrin was localized intracellularly by immunocytochemistry. Finally, alpha IIb and beta 3 mRNAs were amplified by reverse transcription-polymerase chain reaction and the identity of alpha IIb was verified by sequencing. Partial DNA and deduced amino acid sequence analysis showed that B16a alpha IIb shares approximately 80% homology with the human alpha IIb and approximately 90% homology with the rat alpha IIb, whereas B16a alpha IIb shares only approximately 26% homology with the human alpha v. These experiments indicate that the alpha IIb beta 3-like protein in B16a cells is the authentic alpha IIb beta 3 and demonstrate, for the first time, that integrin alpha IIb beta 3 is not confined to megakaryocyte lineage cells. PMID- 1512267 TI - A new inhibitor of metalloproteinases from chicken: ChIMP-3. A third member of the TIMP family. AB - We report cDNA cloning and primary structure of a new metalloproteinase inhibitor (ChIMP-3) produced by chicken embryo fibroblasts. ChIMP-3, formerly called the 21 kDa protein, is one of five ChIMPs (Chicken Inhibitor of MetalloProteinases). In this paper, we report that of the three most abundant ChIMPs, ChIMP-3 and ChIMP-a are extracellular matrix components, whereas ChIMP-2 is found in the media conditioned by the cells. Treatment of ChIMP-3 and ChIMP-a with N-glycosidase-F indicates that ChIMP-a is N-glycosylated whereas ChIMP-3 is not. The deduced amino acid sequence of ChIMP-3 predicts a protein whose properties are consistent with experimental measurements. Analysis of sequence alignments with the two previously described members of the TIMP (tissue inhibitor of metalloproteinases) family, TIMP-1 and TIMP-2, from various species indicates that ChIMP-3 is a related but distinct protein. This conclusion is supported by lack of significant binding with anti-TIMP-1 and anti-TIMP-2 antibodies. Based on these data, its unusual solubility properties, and its exclusive location in the matrix, we propose that ChIMP-3 is a new member of this family of metalloproteinase inhibitors, a TIMP-3. PMID- 1512268 TI - The cytosolic components of the respiratory burst oxidase exist as a M(r) approximately 240,000 complex that acquires a membrane-binding site during activation of the oxidase in a cell-free system. AB - Sodium dodecyl sulfate (SDS) treatment of a mixture of cytosol and plasma membranes from resting neutrophils resulted in the activation of the respiratory burst oxidase, a complicated enzyme that catalyzes the production of O2- from NADPH and oxygen. Activation was accompanied by translocation to the plasma membranes of the oxidase components p47phox and p67phox, which in resting cytosol were found in a M(r) approximately 240,000 complex. This translocation, which appeared to take place without a major change in the size of the cytosolic complex, did not occur if the membranes lacked cytochrome b558, and was inhibited by the peptide PRGV-HFIFNK, a sequence found near the carboxyl terminus of cytochrome b558 that was known from earlier work to inhibit O2- production by the cell-free system (Rotrosen, D., Kleinberg, M. E., Nunoi, H., Leto T., Gallin, J. I., and Malech H. L. (1990) J. Biol. Chem. 265, 8745-8750). Cytosols pretreated with the cross-linking agents 3,3'-dithiobis(sulfosuccinimidyl) propionate (DTSSP) (cleavable by 2-mercaptoethanol) and bis-(sulfosuccinimidyl) suberate (not cleavable by 2-mercaptoethanol) lost most of their ability to support O2- production in the cell-free system, and oxidase components from DTSSP-treated cytosol failed to translocate to the plasma membrane. When DTSSP-treated cytosols were incubated with 2-mercaptoethanol, however, both O2- production and translocation were partly restored, indicating that the functional impairment in DTSSP-treated cytosols was probably due at least in part to a restriction in the conformational mobility of the cross-linked peptide chains in the approximately 240,000 complex. These findings provide further support for the idea that the cytosolic components of the respiratory burst oxidase exist in the form of a approximately 240,000 complex, and suggest that the exposure of this complex to SDS induces a structural change that may or may not be associated with the loss of an inhibitory subunit too small to cause a detectable change in the size of the complex. This SDS-induced change allows translocation to take place by creating a membrane-binding site on the surface of the complex. PMID- 1512269 TI - Molecular cloning and characterization of onchocystatin, a cysteine proteinase inhibitor of Onchocerca volvulus. AB - A cDNA clone designated OV7 encodes a polypeptide that corresponds to a highly antigenic Onchocerca volvulus protein. OV7 has significant amino acid sequence homology to the cystatin superfamily of cysteine proteinase inhibitors. In this report we establish that the OV7 recombinant protein is active as a cysteine proteinase inhibitor, and we have named it onchocystatin. It contains a cystatin like domain that inhibits the activity of cysteine proteinases at physiological concentrations. Recombinant glutathione S-transferase-OV7 (GST-OV7, 1 microM) and maltose-binding protein-OV7 (MBP-OV7, 4 microM) fusion polypeptides inhibit 50% of the enzymatic activity of the bovine cysteine proteinase cathepsin B. Neither fusion polypeptide inhibits serine or metalloproteinases activity. The Ki for GST OV7 fusion polypeptide is 170 nM for cathepsin B and 70 pM or 25 nM for cysteine proteinases purified from a protozoan parasite Entamoeba histolytica or the free living nematode Caenorhabditis elegans, respectively. The 5' end of the OV7 clone was isolated by polymerase chain reaction and sequenced, thus extending the previous cDNA clone to 736 base pairs. This represents the complete coding sequence of the mature onchocystatin (130 amino acids). A hydrophobic leader sequence of 32 amino acids was found, indicating a possible extracellular function of the onchocerca cysteine proteinase inhibitor. PMID- 1512270 TI - Evidence for unequal crossing over in the evolution of the neurofilament polypeptide H. AB - Two allelic forms of the rabbit neurofilament protein H, designated H1 and H2, differ by approximately 6% in their electrophoretic mobilities. We have used techniques of peptide and nucleic acid analysis to determine that this difference is located in the central portion of the COOH-terminal tail, a region of the H protein that can project from the filament, and may form cross-bridges. This region comprises tandem amino acid motifs containing the sequence KSP, in which the serine residues are sites of phosphorylation. The sequence of this repetitive region of H2 is 132 nucleotides (44 amino acids) shorter than H1 and differs significantly in the arrangement of the repeated motifs. The difference suggests that both forms have evolved from a common ancestor over the past several million years by the process of unequal crossing over and that this process figured importantly in generating the repetitive region. In addition, the results indicate that this region is functionally redundant and that the length and structure of the tail of rabbit H resemble H from other mammalian species more closely than was suggested by a previously reported cDNA, on account of a single nucleotide difference. PMID- 1512271 TI - K-ras transformation greatly increases the toxin-dependent ADP-ribosylation of GTP binding proteins in thyroid cells. Involvement of an inhibitor of the ADP ribosylation reaction. AB - The GTP binding (G) proteins of normal (FRTL5) and ras-transformed thyroid cells (KiKi) were characterized by cholera and pertussis toxin-induced ADP-ribosylation and immunoblot analysis. Two pertussis toxin substrates with molecular masses of 40 and 41 kDa were identified in normal cells as the alpha i2 and alpha i3 subunits. The molecular masses of the cholera toxin substrates were 42 and 45 kDa. The same cholera and pertussis toxin substrates were present in the K-ras transformed cell line. However, the toxin-dependent ADP-ribosylation was markedly higher in KiKi than in normal cell membranes (more than 50-fold). The reason for this difference was investigated; it could not be explained by the relative amounts of G proteins in the two cell systems, since the levels of alpha i2 subunit as measured by quantitative immunoblot in K-ras-transformed cells were only slightly (65%) higher than in normal cells. The difference in ADP ribosylation was not due to poly-ADP-ribosylation nor to a different degree of subunit dissociation of G proteins in the two cell lines. Rather, the enhanced ADP-ribosylation in K-ras-transformed cells appears to be due to the loss of an inhibitory factor present in the normal cells. Partial characterization indicates that such a factor is a peripheral membrane protein of less than 25 kDa capable of directly interfering with the ADP-ribosylation reaction. PMID- 1512272 TI - Transforming growth factor beta differentially regulates expression of integrin subunits in guinea pig airway epithelial cells. AB - The integrin family is composed of a large number of heterodimers, each one mediating distinct interactions with extracellular matrix and/or cell surface ligands. The expression of integrins appears to be tightly regulated in vivo, but the mechanisms by which cells control the formation and surface expression of specific pairs of subunits have not been well characterized. Two integrin subunits, the alpha subunit alpha v, and the beta subunit beta 1, could pose special problems in regulation because of their capacity to associate with multiple partners. In the present study, we have examined the effects of the cytokine transforming growth factor beta 1 (TGF-beta 1) on the expression of alpha v- and beta 1-containing integrins in primary cultures of guinea pig airway epithelial cells, e.g. cells that we have previously found to express multiple potential partners for both alpha v and beta 1. TGF-beta 1 increased the surface expression of both alpha v- and beta 1-containing heterodimers after periods of stimulation from 24 to 72 h. These increases in surface expression were associated with significant increases in the concentrations of mRNA encoding each of the partners of alpha v and beta 1, but with only minimal increases in mRNA encoding alpha v and beta 1 themselves. Airway epithelial cells metabolically labeled with [35S]methionine during stimulation with TGF-beta 1 demonstrated only a minimal increase in the synthesis of new alpha v protein at a time when synthesis of alpha v's beta subunit partners and surface expression of alpha v containing heterodimers were dramatically increased. These data suggest that, at least in some cells, promiscuous integrin subunits (both alpha and beta) may normally be synthesized in excess. Thus, the surface expression of specific integrin heterodimers can be regulated primarily through regulation of the synthesis of the specific partners of these subunits. PMID- 1512273 TI - Cruciform extrusion facilitates intramolecular triplex formation between distal oligopurine.oligopyrimidine tracts: long range effects. AB - Two short d(AG)n tracts separated by either of two 40-base pair (bp) inverted repeats adopt a triple-stranded conformation (H-DNA) at the bottom of an extruded cruciform stem in negatively supercoiled plasmids at pH 4.5. Plasmids containing one d(AG)n adjacent to the inverted repeat or containing two d(AG)n tracts separated by a random sequence did not form the triplex structures. These conclusions were derived from chemical modification patterns and UV-sensitivity studies. Two-dimensional agarose gel electrophoresis revealed that the entire insert containing the cruciform and the triplex is locally unlinked. Moreover, a long range structural effect (over 40 bp of random sequence) of one (AG)7 block on the behavior of a second (AG)7 sequence was detected. This effect cannot be transmitted throughout a 50-bp segment of random sequence. A GenBank search revealed the frequent occurrence of short oligopurine blocks with an intervening random sequence of 17-40 bp. PMID- 1512274 TI - Mammalian protein geranylgeranyltransferase. Subunit composition and metal requirements. AB - An enzyme capable of specifically modifying, with a geranylgeranyl isoprenoid, candidate proteins containing a consensus prenylation sequence ending in leucine has been purified from bovine brain. This protein geranylgeranyltransferase (PGGT), isolated using affinity chromatography on an immobilized peptide column, contains two subunits with molecular masses of 48 and 43 kDa, designated alpha and beta, respectively. An antiserum raised to the alpha subunit of the related enzyme, protein farnesyltransferase (PFT), also recognizes this chromatographically identical alpha-subunit of the PGGT by immunoblot analysis. The PGGT and PFT enzymes from bovine brain are shown to be dependent on both Mg2+ and Zn2+ for optimal activity. Demonstration of the Zn2+ dependence of the enzymes requires prolonged incubation or purification in the presence of a chelating agent; we therefore propose that these enzymes be placed into the category of metalloenzymes. Under optimal assay conditions, these enzymes show high specificity toward their prenyl diphosphate substrates, with only a weak competition observed with farnesyl diphosphate in the PGGT reaction or geranylgeranyl diphosphate in the PFT reaction. The two enzymes are differentially sensitive to several detergents tested to determine suitable ones for product stabilization in the reactions. These results confirm previous predictions on the subunit structure of the PGGT and provide an avenue to initiating a molecular analysis of the geranylgeranyl modification of many mammalian proteins. PMID- 1512276 TI - Evidence for the translational control of storage protein gene expression in oat seeds. AB - We employed a rapid fractionation method coupled with a sensitive enzyme-linked immunosorbent assay to quantify the globulins and avenins in developing and mature oat seeds. On a molar basis, there is approximately 10-11 times as much globulin as avenin. Pulse labeling of endosperm proteins indicated that the rate of globulin synthesis is approximately nine times that of avenin. In addition, neither protein class showed any signs of degradation during this experiment. Analysis of the storage protein mRNAs indicates that both globulin and avenin transcripts are associated with membrane-bound polysomes and are found in similar concentrations within the membrane-bound polysome fraction. We found that avenin and globulin mRNAs are fully loaded with ribosomes, suggesting that initiation is not rate-limiting for translation of either protein. Rates of globulin and avenin synthesis were similar when synthetic storage protein mRNAs were translated in vitro. Translation of equimolar amounts of globulin and avenin mRNAs in the same reaction showed equivalent amounts of protein synthesized when compared with globulin and avenin mRNAs translated in separate reaction mixes. We propose that translation elongation or termination reactions are likely regulatory steps for controlling storage protein synthesis in oat endosperm. PMID- 1512275 TI - Platelet-derived growth factor regulation of fos stability correlates with growth induction. AB - A brief exposure of quiescent, density-arrested Balb/c 3T3 fibroblasts to platelet-derived growth factor (PDGF) results in expression of the proto-oncogene c-fos; furthermore, the translation product of c-fos, p55fos, was shown to have increased stability in cells upon continued exposure to PDGF. The induction of competence or growth initiation requires a longer exposure to PDGF than that necessary for the induction of the immediate-early, growth-related genes. The need for the continued presence of PDGF for growth initiation beyond the time required for the induction of immediate-early gene expression may be due, in part, to PDGF-dependent post-translational stabilizations of gene products. We speculate that a PDGF-mediated event increases p55fos stability, resulting in a continued elevated level of Fos protein, which in turn allows a continued Fos mediated activity required by Balb/c 3T3 cells to become competent to enter the cell cycle. PMID- 1512277 TI - Further analysis of the inhibitory effects of dihydroergotamine, cyproheptadine and ketanserin on the responses of the rat aorta to 5-hydroxytryptamine. AB - 1. The aim of the present study was to analyse the inhibitory effects of dihydroergotamine, cyproheptadine and ketanserin on the rat aorta contractile responses to 5-HT. Initially phenoxybenzamine treatment was used to determine whether spare receptors exist at the maximum responses to 5-HT. Then the reversibility of the inhibitory effects of phentolamine, dihydroergotamine, cyproheptadine and ketanserin against the fast and slow response of the rat aorta to 5-HT were determined. 2. Phenoxybenzamine caused non-parallel rightward shifts of the 5-HT concentration-response curves with reduced maximal responses. The KA values for 5-HT to produce fast and slow responses were 2-5 x 10(-5) M. These KA values are much higher than those previously reported for 5-HT at 5-HT2-receptors and suggest that the 5-HT2-receptor of the rat aorta is 'atypical'. The rat aorta has spare 5-HT-receptors for the maximal fast and slow responses to 5-HT. 3. Phentolamine, dihydroergotamine, cyproheptadine and ketanserin inhibited the fast and slow responses to 5-HT. Phentolamine and ketanserin and the higher concentrations of dihydroergotamine and cyproheptadine tested had greater inhibitory effects on the fast than slow 5-HT responses possibly because the fast 5-HT response did not always reach equilibrium in the presence of antagonists. 4. The inhibitory effects on 5-HT responses of phentolamine at 10(-6)-10(-5) M were readily reversible, those of cyproheptadine at 10(-9)-10(-8) M and ketanserin at 10(-8) M were slowly reversible and those of dihydroergotamine at 10(-9)-10(-8) M were irreversible by washing in drug-free Krebs. 5. The inhibitory effects of phentolamine and ketanserin were not altered by increasing the treatment time whereas some of the effects of cyproheptadine and the effects of dihydroergotamine on responses to 5-HT were increased by prolonging the contact time with the antagonist from 75 to 150 min. 6. The present study shows that at the rat aorta 5-HT2-receptor, phentolamine is a competitive readily reversible, cyproheptadine and ketanserin are competitive slowly reversible and dihydroergotamine is a competitive irreversible antagonist. PMID- 1512278 TI - Effects of the divalent cations nickel and cadmium on contractions of rat aorta to endothelin-1. AB - 1. The effects of inorganic and organic calcium channel antagonists on the contractile responses of rat isolated aortic rings to endothelin-1 (ET-1) were studied. 2. ET-1 (0.1-100 nM) evoked concentration-related contractile responses of the rat aorta (EC50 1.65 +/- 0.22 nM, Emax 125.8 +/- 4.5 %KClmax, n = 20). In Ca(2+)-free modified Krebs solution (containing 1 mM EGTA) aortic rings failed to contract to ET-1 (0.1-30 nM). 3. Nickel chloride (0.2-0.8 mM) attenuated the ET-1 (1-100 nM)-induced contraction of rat aorta (response (%KClmax) to 10 nM ET-1: control 132.0 +/- 8.7 and after 0.2 mM Ni2+ 90.3 +/- 14.8, 0.4 mM Ni2+ 54.7 +/- 12.3, 0.8 mM Ni2+ 10.3 +/- 4.4, n = 6/group). Cadmium chloride (10-30 microM) depressed the maxima of the concentration-response curves to ET-1 with an IC50 of 15.4 +/- 1.5 microM (n = 6). 4. The ET-1 evoked contractile responses were not modified by the dihydropyridine calcium channel antagonist, nicardipine (0.1 microM), or by omega-conotoxin (1.0 microM). Cinnarizine (10 microM), however, significantly attenuated the maximum response to ET-1 (96.9 +/- 6.0 vs 128.0 +/- 5.8 %KClmax for control), but failed to modify the EC50 value. 5. Amiloride, a Na(+)-Ca2+ exchange inhibitor, also depressed the maxima of the concentration response curves to ET-1 with an IC50 of 0.45 +/- 0.05 mM (n = 4).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1512279 TI - Bone apposition to plasma-sprayed cobalt-chromium alloy. AB - The use of porous metallic coatings for fixation of total joint prostheses by bone ingrowth has become a widespread alternative to fixation with PMMA bone cement. However, concerns about such coatings include long-term effects of metal ion release, potential coating loss, and decreased substrate fatigue strength. The biological fixation capability of a nonporous, high-integrity plasma-sprayed CoCr coating with low surface area was compared to a conventional sintered bead coating in goat cortical and cancellous bone sites after 8 and 16 weeks of implantation. Histological evaluation showed substantial variations in fixation quality between individual animals and between surgical sites with no consistent difference between implant types. Shear testing of bone/implant interfaces showed that although conventional porous coating exhibited higher overall average shear strengths in cortical bone sites at both time periods, the differences were not statistically significant. In cancellous sites, the average shear strengths achieved with conventional porous and plasma-sprayed coatings were essentially equal. Analysis using average paired differences, however, revealed that when porous and plasma-coated implants are placed in identical sites of contralateral limbs, the plasma coatings consistently yielded higher shear strengths in cancellous bone sites at the later time period. Since current design theory for biological fixation favors metaphysical fixation, this surface may offer potential advantages over conventional porous coatings. PMID- 1512280 TI - Preparation and thrombogenicity of alkylated polyvinyl alcohol coated tubing. AB - A polyvinyl alcohol hydrogel (PVA) was reacted with a C18 isocyanate at 80 degrees C in dimethyl formamide (DMF) in order to improve the platelet reactivity of the hydrogel through an influence on albumin adsorption or retention. A C4 isocyanate was used as a control. Surface coverage by XPS appeared to be approximately 100% for both C4 and C18 modified surfaces, although the limited solubility of C18 isocyanate in DMF may have resulted in a nonuniform surface. Relative to PVA or the solvent treated control, octadecylation resulted in increased albumin adsorption (from a single protein solution) and increased retention when the adsorbed albumin was exposed to a fibrinogen solution. However, octadecylation did not obviate the platelet reactivity problem in preliminary studies: systemic platelet counts were reduced by about half over 4 days in a canine AV shunt experiment and the initial rate of platelet destruction for C18-PVA was greater (36%/day) even than for the solvent-treated PVA. Surprisingly in preliminary studies butylation of PVA resulted in little or no thrombocytopenia and did not appear to increase significantly the fractional rate of platelet destruction relative to the shunt only blank. It is presumed that the nonspecific effect of alkylation (independent of chain length) was the dominant contribution to the reduced platelet reactivity. A similar effect of C18-PVA presumably would have been observed had the limited solubility of C18 isocyanate not precluded a uniform surface coverage. PMID- 1512281 TI - Development of FRP composite structural biomaterials: ultimate strength of the fiber/matrix interfacial bond in in vivo simulated environments. AB - Fiber reinforced polymer (FRP) composites are being developed as alternatives to metals for structural orthopedic implant applications. FRP composite fracture behavior and environmental interactions are distinctly different from those which occur in metals. These differences must be accounted for in the design and evaluation of implant performance. Fiber/matrix interfacial bond strength in a FRP composite is known to strongly influence fracture behavior. The interfacial bond strength of four candidate fiber/matrix combinations (carbon fiber/polycarbonate, carbon fiber/polysulfone, polyaramid fiber/polycarbonate, polyaramid fiber/polysulfone) were investigated at 37 degrees C in dry and in vivo simulated (saline, exudate) environments. Ultimate bond strength was measured by a single fiber-microdroplet pull-out test. Dry bond strengths were significantly decreased following exposure to either saline or exudate with bond strength loss being approximately equal in both the saline and exudate. Bond strength loss is attributed to the diffusion of water and/or salt ions into the sample and their interaction with interfacial bonding. Because bond degradation is dependent upon diffusion, diffusional equilibrium must be obtained in composite test samples before the full effect of the test environment upon composite mechanical behavior can be determined. PMID- 1512282 TI - A comparative evaluation of the biostability of a poly (ether urethane) in the intraocular, intramuscular, and subcutaneous environments. AB - A transparent poly (ether urethane) (PEU) was considered for use as a foldable intraocular lens material. The PEU was found to possess excellent mechanical, optical, and surface characteristics for this application. In vitro hydrolytic and ultraviolet aging studies suggested the PEU to be tolerant to conditions simulating 3-10 years of normal intraocular exposure. Different behavior was obtained, however, from intraocular and subcutaneous implantation of the PEU. After 6 months of intraocular exposure in the feline model, prototype PEU lenses had lost most or all of their optical resolving power. SEM analysis demonstrated scattered pitting and cracking on the lens surfaces. Degradation was found to be more extreme after as little as 30 days of subcutaneous exposure in rabbits. Severe pitting over the entire surface of implanted flat PEU specimens was observed by SEM. Macroscopic examination showed the samples to be frosty in appearance. It was postulated that the subcutaneous implant environment provides an accelerated in vivo model for materials intended for intraocular use. A minimum acceleration of 6-10x was estimated on a preliminary basis. The PEU studied here was found to be unsuitable for use as a foldable intraocular lens material. PMID- 1512284 TI - A fractographic investigation of PMMA bone cement focusing on the relationship between porosity reduction and increased fatigue life. AB - Fracture surfaces of both monotonic and fatigue loaded bone cement samples were examined to investigate the fractographic characteristics of PMMA. Classic cleavage step river patterns were observed on all monotonically loaded samples, running downstream in the direction of crack propagation. All fatigue cracks initiated at internal pores and the direction of crack propagation of many cracks was discernible. Porosity, pore size, and pore size distribution were found to affect the crack initiation and fatigue behavior of bone cement. Statistical analysis revealed a strong negative correlation between two-dimensional porosity present on the fracture surfaces and the cycles to failure. The fractographic observations of these fatigue samples elucidate one reason why porosity reduction by centrifugation or vacuum mixing increases the fatigue life of PMMA bone cement. PMID- 1512283 TI - Difference in tumor incidence and other tissue responses to polyetherurethanes and polydimethylsiloxane in long-term subcutaneous implantation into rats. AB - The long-term (1- and 2-year) adverse tissue responses including tumor formation by subcutaneous implantation of polyurethanes (PUs) and silicone (Sil) films into rats were compared. The weight-averaged molecular weights (Mw) of the PUs prepared from 4,4'-diphenylmethanediisocyanate, poly(tetramethyleneglycol) of Mn = 1000 and 1,4-butanediol are 220,000 (U-4), 124,000 (U-6), and 55,600 (U-8). The 50:50 mixed film of U-6 and silicone (U-6/sil) was prepared by roll-mixing of the noncured silicone and the U-6 solution followed by evaporation of the solvent and heat-curing at 70 degrees C. The tissue responses around implants were classified into four groups as follows: (A) tumor, (B) atypical cell proliferation accompanied by preneoplastic changes, (C) cell proliferation without preneoplastic changes, (D) no obvious responses. In both implantation periods, the PUs gave higher incidents of the adverse responses including tumor formation in comparison to Sil. No significant molecular weight-dependent trend was found in a 1-year study using U-4, 6, and 8. Significant PU-dose-dependent trends were found in a 2-year study: the total active incidence (A+B+C), U-6(22/29) greater than U-6/sil(11/29) greater than sil(7/28); tumor incidence (A), U-6(11/29) greater than U-6/sil(2/29) = sil(2/28). No detectable amounts of 4,4' methylenedianiline (MDA) were found in the PUs. The methanol extracts from the PUs were negative in the mutagenicity tests. These indicate no relationship between the tumor formation by the PU films and the mutagenicities of the chemicals (mainly oligomers) leached from the PUs. PMID- 1512285 TI - Measurement of the rate of thrombin production in human plasma in contact with different materials. AB - Thrombin production in plasma in contact with various materials was consistent with a first-order autocatalytic model (d[T]/dt = kp[T]; [T] = thrombin concentration, t = time, kp = thrombin production rate constant) since the initial portion of a semilogarithmic plot of thrombin concentration against time was linear. Thrombin concentration was measured in clotting plasma (phospholipid enhanced or platelet-rich plasma) using a fluorogenic substrate (BMCA) by aliquot sampling at various intervals or more conveniently by monitoring cumulative fluorescence. The latter was generated by the action, on BMCA incubated in the clotting plasma, of the thrombin as it was generated. The thrombin concentration was determined from the first derivative of the S-shaped cumulative fluorescence curve. kp was greater for glass (7.92 x 10(-3) cm/s) than for the other materials (polypropylene, polystyrene, polyethylene and PVA; kp approximately 3.1 x 10(-3) cm/s) in plasma with cephalin without flow. A kp for heparin-PVA could not be determined since the thrombin concentration was too low to be quantified. A larger difference between polyethylene and PVA was noted with platelet-rich plasma without flow while lower values (1.0 x 10(-3) cm/s) were noted in a flow system but at a higher surface to volume ratio. The first-order rate constant can be used in simple models relating production of thrombin at a wall of a tube to its mass transfer away from the wall in flowing blood. One such model predicts that the concentration of thrombin at the wall should become infinite at the point in the tube when the mass transfer coefficient equals kp. According to this model, kp on the order of 10(-4) cm/s would be a useful target for a nonthrombogenic material. PMID- 1512286 TI - VIP21, a 21-kD membrane protein is an integral component of trans-Golgi-network derived transport vesicles. AB - In simple epithelial cells, apical and basolateral proteins are sorted into separate vesicular carriers before delivery to the appropriate plasma membrane domains. To dissect the putative sorting machinery, we have solubilized Golgi derived transport vesicles with the detergent CHAPS and shown that an apical marker, influenza haemagglutinin (HA), formed a large complex together with several integral membrane proteins. Remarkably, a similar set of CHAPS-insoluble proteins was found after solubilization of a total cellular membrane fraction. This allowed the cloning of a cDNA encoding one protein of this complex, VIP21 (Vesicular Integral-membrane Protein of 21 kD). The transiently expressed protein appeared on the Golgi-apparatus, the plasma membrane and vesicular structures. We propose that VIP21 is a component of the molecular machinery of vesicular transport. PMID- 1512287 TI - A novel 115-kD peripheral membrane protein is required for intercisternal transport in the Golgi stack. AB - We have used an in vitro Golgi protein transport assay dependent on high molecular weight (greater than 100 kD) cytosolic and/or peripheral membrane proteins to study the requirements for transport from the cis- to the medial compartment. Fractionation of this system indicates that, besides the NEM sensitive fusion protein (NSF) and the soluble NSF attachment protein (SNAP), at least three high molecular weight protein fractions from bovine liver cytosol are required. The activity from one of these fractions was purified using an assay that included the second and third fractions in a crude state. The result is a protein of 115-kD subunit molecular mass, which we term p115. Immunodepletion of the 115-kD protein from a purified preparation with mAbs removes activity. Peptide sequence analysis of tryptic peptides indicates that p115 is a "novel" protein that has not been described previously. Gel filtration and sedimentation analysis indicate that, in its native state, p115 is a nonglobular homo-oligomer. p115 is present on purified Golgi membranes and can be extracted with high salt concentration or alkaline pH, indicating that it is peripherally associated with the membrane. Indirect immunofluorescence indicates that p115 is associated with the Golgi apparatus in situ. PMID- 1512288 TI - The pathway and targeting signal for delivery of the integral membrane glycoprotein LEP100 to lysosomes. AB - A complete set of chimeras was made between the lysosomal membrane glycoprotein LEP100 and the plasma membrane-directed vesicular stomatitis virus G protein, combining a glycosylated lumenal or ectodomain, a single transmembrane domain, and a cytosolic carboxyl-terminal domain. These chimeras, the parent molecules, and a truncated form of LEP100 lacking the transmembrane and cytosolic domains were expressed in mouse L cells. Only LEP100 and chimeras that included the cytosolic 11 amino acid carboxyl terminus of LEP100 were targeted to lysosomes. The other chimeras accumulated in the plasma membrane, and truncated LEP100 was secreted. Chimeras that included the extracellular domain of vesicular stomatitis G protein and the carboxyl terminus of LEP100 were targeted to lysosomes and very rapidly degraded. Therefore, in chimera-expressing cells, virtually all the chimeric molecules were newly synthesized and still in the biosynthesis and lysosomal targeting pathways. The behavior of one of these chimeras was studied in detail. After its processing in the Golgi apparatus, the chimera entered the plasma membrane/endosome compartment and rapidly cycled between the plasma membrane and endosomes before going to lysosomes. In pulse-expression experiments, a large population of chimeric molecules was observed to appear transiently in the plasma membrane by immunofluorescence microscopy. Soon after protein synthesis was inhibited, this surface population disappeared. When lysosomal proteolysis was inhibited, chimeric molecules accumulated in lysosomes. These data suggest that the plasma membrane/early endosome compartment is on the pathway to the lysosomal membrane. This explains why mutations that block endocytosis result in the accumulation of lysosomal membrane proteins in the plasma membrane. PMID- 1512289 TI - Sec8p and Sec15p are components of a plasma membrane-associated 19.5S particle that may function downstream of Sec4p to control exocytosis. AB - The SEC8 and SEC15 genes are essential for exocytosis in the yeast Saccharomyces cerevisiae and exhibit strong genetic interactions with SEC4, a gene of the ras superfamily. The SEC8 gene encodes a hydrophilic protein of 122 kD, while the temperature-sensitive sec8-9 allele encodes a protein prematurely truncated at 82 kD by an opal stop codon. The Sec8p sequence contains a 202 amino acid region that is 25% identical to the leucine rich domain of yeast adenylate cyclase that has been implicated in ras responsiveness. Fractionation, stability, and cross linking studies indicate that Sec8p is a component of a 19.5S particle that also contains Sec15p. This particle is found both in the cytosol and peripherally associated with the plasma membrane, but it is not associated with secretory vesicles. Gel filtration studies suggest that a portion of Sec4p is in association with the Sec8p/Sec15p particle. We propose that this particle may function as a downstream effector of Sec4p, serving to direct the fusion of secretory vesicles with the plasma membrane. PMID- 1512290 TI - Isolation of insoluble secretory product from bovine thyroid: extracellular storage of thyroglobulin in covalently cross-linked form. AB - Extracellular storage of thyroglobulin (TG) is an important prerequisite for maintaining constant levels of thyroid hormones in vertebrates. Storage of large amounts is made possible by compactation of TG in the follicle lumen with concentrations of at least 100-400 mg/ml. We recently observed that the luminal content from bovine thyroids can be isolated in an intact state and be separated from soluble TG. For this purpose, bovine thyroid tissue was homogenized and subjected to various steps of purification. This procedure resulted in a pellet of single globules measuring 20-120 microns in diameter. Scanning electron microscopy revealed a unique cobblestone-like surface pattern of isolated globules, showing in detail the impressions of the apical plasma membranes of thyrocytes which had formerly surrounded the luminal content before tissue homogenization. Isolated thyroid globules were rapidly digested by trypsin but extremely resistant to various protein solubilization procedures. Homogenization of isolated globules resulted in the release of approximately 3% of total protein, showing that only a minor proportion of TG was loosely incorporated in thyroid globules whereas approximately 22% appeared to be interconnected with the globule matrix by disulfide bridges. Analysis by SDS-gel electrophoresis and immunoblotting confirmed that the protein released by this procedure consisted of TG. The vast majority (approximately 75%) of the globule matrix protein was found to be covalently cross-linked by non-disulfide bonds. TG in isolated globules was highly iodinated (approximately 55 iodine atoms per 12-S TG subunit) suggesting that the covalent nondisulfide cross-linking occurs in part during the iodination of TG and that this process involves the formation of intermolecular dityrosine bridges. Mechanisms must exist which solubilize or disperse the insoluble luminal content prior to endocytosis of TG. PMID- 1512291 TI - Role of the COOH-terminal nonhelical tailpiece in the assembly of a vertebrate nonmuscle myosin rod. AB - A short nonhelical sequence at the COOH-terminus of vertebrate nonmuscle myosin has been shown to enhance myosin filament assembly. We have analyzed the role of this sequence in chicken intestinal epithelial brush border myosin, using protein engineering/site-directed mutagenesis. Clones encoding the rod region of this myosin were isolated and sequenced. They were truncated at various restriction sites and expressed in Escherichia coli, yielding a series of mutant myosin rods with or without the COOH-terminal tailpiece and with serial deletions from their NH2-termini. Deletion of the 35 residue COOH-terminal nonhelical tailpiece was sufficient to increase the critical concentration for myosin rod assembly by 50 fold (at 150 mM NaCl, pH 7.5), whereas NH2-terminal deletions had only minor effects. The only exception was the longest NH2-terminal deletion, which reduced the rod to 119 amino acids and rendered it assembly incompetent. The COOH terminal tailpiece could be reduced by 15 amino acids and it still efficiently promoted assembly. We also found that the tailpiece promoted assembly of both filaments and segments; assemblies which have different molecular overlaps. Rod fragments carrying the COOH-terminal tailpiece did not promote the assembly of COOH-terminally deleted material when the two were mixed together. The tailpiece sequence thus has profound effects on assembly, yet it is apparently unstructured and can be bisected without affecting its function. Taken together these observations suggest that the nonhelical tailpiece may act sterically to block an otherwise dominant but unproductive molecular interaction in the self assembly process and does not, as has been previously thought, bind to a specific target site(s) on a neighboring molecule. PMID- 1512292 TI - Kinectin, a major kinesin-binding protein on ER. AB - Previous studies have shown that microtubule-based organelle transport requires a membrane receptor but no kinesin-binding membrane proteins have been isolated. Chick embryo brain microsomes have kinesin bound to their surface, and after detergent solubilization, a matrix with an antibody to the kinesin head domain (SUK-4) (Ingold et al., 1988) bound the solubilized kinesin and retained an equal amount of a microsome protein of 160-kD. Similarly, velocity sedimentation of solubilized membranes showed that kinesin and the 160-kD polypeptide cosedimented at 13S. After alkaline treatment to remove kinesin from the microsomes, the same 160-kD polypeptide doublet bound to a kinesin affinity resin and not to other proteins tested. Biochemical characterization localized this protein to the cytoplasmic face of brain microsomes and indicated that it was an integral membrane protein since it was resistant to alkaline washing. mAbs raised to chick 160-kD protein demonstrated that it was absent in the supernatant and concentrated in the dense microsome fraction. The dense microsome fraction also had the greatest amount of microtubule-dependent motility. With immunofluorescence, the antibodies labeled the ER in chick embryo fibroblasts (similar to the pattern of bound kinesin staining in the same cells) (Hollenbeck, P. J. 1989. J. Cell Biol. 108:2335-2342), astroglia, Schwann cells and dorsal root ganglion cells but staining was much less in the Golgi regions of these cells. Because this protein is a major kinesin-binding protein of motile vesicles and would be expected to bind kinesin to the organelle membrane, we have chosen the name, kinectin, for this protein. PMID- 1512293 TI - Transcripts for the acetylcholine receptor and acetylcholine esterase show distribution differences in cultured chick muscle cells. AB - In situ hybridization of chick cultured muscle cells using exonic DNA probes for both AChR alpha-sub-unit and the catalytic subunit of AChE, revealed major differences in the distribution of label both over nuclei and in their surrounding cytoplasm, although some overlap in these distributions exists. For the AChR alpha-subunit there is a highly skewed distribution of labeled nuclei, with 35% of the nuclei being relatively inactive (less than 0.25 times the mean label) and approximately 10% being very heavily labeled (greater than 2.5 times the mean label). In contrast the nuclei labeled with the exonic probe for the AChE transcripts had a more Gaussian distribution, yet with some slight skewness in the direction of a few heavily labeled nuclei. There was also a difference in the cytoplasmic distribution of the label. The AChR alpha-subunit mRNA was mainly within 4 microns of labeled nuclei while the AChE mRNA was more widely distributed throughout the cytoplasm, possibly within a 10 microns rim around labeled nuclei. An intronic probe for the AChE gave the identical distribution of nuclear label to that of the exonic probe (but without any cytoplasmic label). In addition, calibration of the technique indicated that per myotube the AChE transcript is about sixfold more abundant than the AChR alpha-subunit transcript. PMID- 1512294 TI - A GTPase controls cell-substrate adhesion in Xenopus XTC fibroblasts. AB - Cell-substrate adhesion is crucial at various stages of development and for the maintenance of normal tissues. Little is known about the regulation of these adhesive interactions. To investigate the role of GTPases in the control of cell morphology and cell-substrate adhesion we have injected guanine nucleotide analogs into Xenopus XTC fibroblasts. Injection of GTP gamma S inhibited ruffling and increased spreading, suggesting an increase in adhesion. To further investigate this, we made use of GRGDSP, a peptide which inhibits binding of integrins to vitronectin and fibronectin. XTC fibroblasts injected with non hydrolyzable analogs of GTP took much more time to round up than mock-injected cells in response to treatment with GRGDSP, while GDP beta S-injected cells rounded up in less time than controls. Injection with GTP gamma S did not inhibit cell rounding induced by trypsin however, showing that cell contractility is not significantly affected by the activation of GTPases. These data provide evidence for the existence of a GTPase which can control cell-substrate adhesion from the cytoplasm. Treatment of XTC fibroblasts with the phorbol ester 12-o tetradecanoylphorbol-13-acetate reduced cell spreading and accelerated cell rounding in response to GRGDSP, which is essentially opposite to the effect exerted by non-hydrolyzable GTP analogs. These results suggest the existence of at least two distinct pathways controlling cell-substrate adhesion in XTC fibroblasts, one depending on a GTPase and another one involving protein kinase C. PMID- 1512295 TI - Nectadrin, the heat-stable antigen, is a cell adhesion molecule. AB - Nectadrin, the cell surface glycoprotein recognized by the novel mAb 79, was found to be immunologically identical to the heat-stable antigen (HSA). It is a glycoprotein with a polypeptide core of only 30 amino acids and a very high carbohydrate content (Wenger, R. H., M. Ayane, R. Bose, G. Kohler, and P. J. Nielsen. 1991. Eur. J. Immunol. 21:1039-1046). Immunocytological studies using cultured splenic B-lymphocytes, neuroblastoma cells, and cerebellar cells indicated that nectadrin is preferentially expressed at sites of cell-cell contact. Purified nectadrin and monoclonal nectadrin antibody 79, but not other monoclonal nectadrin antibodies, inhibited the aggregation of B-lymphocytes by 70%, suggesting that nectadrin may act as a cell adhesion molecule. Nectadrin was purified from a mouse lymphoma cell line in two forms of 40-60 and 23-30 kD. The lower molecular weight form appears to be generated from the higher molecular weight form by degradative removal of saccharide residues characteristic of complex type oligosaccharide side chains. Latex beads coated with purified nectadrin aggregated and the rate of their aggregation depended on the molecular form of nectadrin, with the larger form being more potent than the smaller one in mediating bead aggregation. Nectadrin thus appears to be a self-binding cell adhesion molecule of a structurally novel type in that its extensive glycan structures may be implicated in mediating cell adhesion. PMID- 1512296 TI - Bravo/Nr-CAM is closely related to the cell adhesion molecules L1 and Ng-CAM and has a similar heterodimer structure. AB - Diverse cell-surface molecules of the nervous system play an important role in specifying cell interactions during development. Using a method designed to generate mAbs against neural surface molecules of defined molecular weight, we have previously reported on the surface protein, Bravo, found in the developing avian retinotectal system. Bravo is immunologically detected on developing optic fibers in the retina, but absent from distal regions of the same fibers in the tectum. We have isolated cDNA clones encompassing the entire coding region of Bravo, including clones containing five alternative sequences of cDNA. These putative alternatively spliced sequences encode stretches of polypeptide ranging in length from 10-93 amino acids and are predicted to be both extra- and intracellular. The deduced primary structure of Bravo reveals that, like the cell adhesion molecules (CAMs) chicken Ng-CAM and mouse L1, Bravo is composed of six Ig-like domains, five fibronectin type III repeats, a transmembrane domain, and a short cytoplasmic region. Recently, the cDNA sequence of a related molecule, Nr CAM, was reported and its possible identity with Bravo discussed (Grumet, M., V. Mauro, M. P. Burgoon, G. E. Edelman, and B. A. Cunningham. 1991. J. Cell Biol. 113:1399-1412). Here we confirm this identity and moreover show that Bravo is found on Muller glial processes and end-feet in the developing retina. In contrast to the single polypeptide chain structure of Nr-CAM reported previously, we show that Bravo has a heterodimer structure composed of an alpha chain of M(r) 140/130 and a beta chain of 60-80 kD. As with L1 and Ng-CAM, the two chains of Bravo are generated from an intact polypeptide by cleavage at identical locations and conserved sites within all three molecules (Ser-Arg/Lys-Arg). The similar domain composition and heterodimer structure, as well as the 40% amino acid sequence identity of these molecules, defines them as an evolutionarily related subgroup of CAMs. The relationship of Bravo to molecules known to be involved in cell adhesion and process outgrowth, combined with its pattern of expression and numerous potential isoforms, suggests a complex role for this molecule in cell interactions during neural development. PMID- 1512298 TI - Biological properties of interleukin 10. PMID- 1512297 TI - Coordinated expression of extracellular matrix-degrading proteinases and their inhibitors regulates mammary epithelial function during involution. AB - Extracellular matrix (ECM) plays an important role in the maintenance of mammary epithelial differentiation in culture. We asked whether changes in mouse mammary specific function in vivo correlate with changes in the ECM. We showed, using expression of beta-casein as a marker, that the temporal expression of ECM degrading proteinases and their inhibitors during lactation and involution are inversely related to functional differentiation. After a lactation period of 9 d, mammary epithelial cells maintained beta-casein expression up to 5 d of involution. Two metalloproteinases, 72-kD gelatinase (and its 62-kD active form), and stromelysin, and a serine proteinase tissue plasminogen activator were detected by day four of involution, and maintained expression until at least day 10. The expression of their inhibitors, the tissue inhibitor of metalloproteinases (TIMP) and plasminogen activator inhibitor-1, preceded the onset of ECM-degrading proteinase expression and was detected by day two of involution, and showed a sharp peak of expression centered on days 4-6 of involution. When involution was accelerated by decreasing lactation to 2 d, there was an accelerated loss of beta-casein expression evident by day four and a shift in expression of ECM-remodeling proteinases and inhibitors to a focus at 2-4 d of involution. To further extend the correlation between mammary-specific function and ECM remodeling we initiated involution by sealing just one gland in an otherwise hormonally sufficient lactating animal. Alveoli in the sealed gland contained casein for at least 7 d after sealing, and closely resembled those in a lactating gland. The relative expression of TIMP in the sealed gland increased, whereas the expression of stromelysin was much lower than that of a hormone depleted involuting gland, indicating that the higher the ratio of TIMP to ECM degrading proteinases the slower the process of involution. To test directly the functional role of ECM-degrading proteinases in the loss of tissue-specific function we artificially perturbed the ECM-degrading proteinase-inhibitor ratio in a normally involuting gland by maintaining high concentrations of TIMP protein with the use of surgically implanted slow-release pellets. In a concentration dependent fashion, involuting mammary glands that received TIMP implants maintained high levels of casein and delayed alveolar regression. These data suggest that the balance of ECM-degrading proteinases and their inhibitors regulates the organization of the basement membrane and the tissue-specific function of the mammary gland.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1512299 TI - Conjunctival epithelial cells from patients with Sjogren's syndrome inappropriately express major histocompatibility complex molecules, La(SSB) antigen, and heat-shock proteins. AB - The La(SSB) antigen has been detected within the cytoplasm and on the membrane of conjunctival cells (CC) from patients with Sjogren's syndrome, whereas it was weakly expressed in the nucleus of normal cells. The diseased CC were shown to overproduce major histocompatibility complex (MHC) class I antigens and express MHC class II antigens. Anti-heat-shock protein monoclonal antibody bound to the cell membrane in patients but not in normal controls. PMID- 1512300 TI - Chronic enteroviral meningoencephalitis in agammaglobulinemia: case report and literature review. AB - Chronic enteroviral meningoencephalitis is a well-recognized complication in patients with X-linked agammaglobulinemia (XLA). The majority of published cases refers to its occurrence in patients on no replacement therapy or on only intramuscular immunoglobulin. The advent of intravenous immunoglobulin (IVIg) in the early 1980s and its widespread use in XLA was thought to have virtually eradicated enteroviral meningoencephalitis in these patients. We describe the development of echovirus meningoencephalitis in an 11-year-old boy on regular IVIg replacement whose serum IgG levels were maintained at between 6 and 8 g/L (NR 6-13 g/L). Treatment with daily high-dose IVIg was commenced, with significant clinical improvement being noted within a few weeks in association with a reduction in blood-brain barrier permeability. The persistence of live virus, however, necessitated the use of intraventricular immunoglobulin. The virus proved resistant to two courses of specific intraventricular immunoglobulin and a 6-week course of oral ribavirin and eventually proved fatal 5 months after presentation. In view of the therapeutic uncertainties we have reviewed the use of immunoglobulin in the treatment of enteroviral meningoencephalitis over the past 6 years. PMID- 1512301 TI - Major histocompatibility complex (MHC) class II restriction, lymphokine production, and IgE regulation of house dust mite-specific T-cell clones. AB - To elucidate the regulatory mechanism of human IgE synthesis, we have cloned house dust mite (Dermatophagoides pteronyssinus; Dp)-specific T-cell clones from three asthmatic children and three healthy individuals. Twelve clones were cloned from each group. All of these clones were CD3+, CD4+, CD8-, and HLA-DR+. After stimulation with allergen in the presence of antigen presenting cells (APCs), half of the T-cell clones from asthmatic children and one-third of those from normals produced interleukin 4 (IL-4). None of the patients' clones produced interferon gamma (IFN-gamma), while 10 of 12 normals' clones did. After stimulation with calcium ionophore A23187 and phorbol myristic acetate (PMA), the production of IL-4 was markedly increased in both patients and normals. However, only 3 of the 12 patients' clones produced IFN-gamma, while all of the normals' clones did. The T-cell clones of both patients and normals produced comparable IL 2. To study the kinetics of lymphokine productions, a HLA-DRw12-restricted T-cell clone (FYD 3.1) was stimulated, respectively, with a combination of A23187 and PMA, phytohemagglutinin (PHA), or Dp antigen in the presence of APCs. Maximal IL 2 and IL-4 productions were detected 12 hr after A23187 and PMA stimulation, whereas IFN-gamma could not be detected even 36 hr after stimulation. When stimulated with PHA, the production of IFN-gamma peaked on the fourth day, but IL 4 was not detected. After stimulation with Dp antigen and APCs, IL-4 and IL-2 were detected on the second and third days, but IFN-gamma was not detected. The IgE production by autologous purified B cells in the presence of allergen or IL-4 was found to be augmented by the FYD 3.1 T-cell clones. IFN-gamma was observed to counteract the effects of the T-cell clones and IL-4. Thus, the secretory patterns of lymphokine and kinetics of lymphokine production of allergen-specific T-cell clones can be used to explore the regulatory mechanism of human IgE synthesis [corrected]. PMID- 1512302 TI - Induction of lymphokine-activated killer cells with low-dose interleukin 2 and interferon-gamma in oral cancer patients. AB - Lymphokine-activated killer (LAK) cells were induced with low-dose recombinant interleukin 2 (rIL-2) and recombinant interferon-gamma (IFN-gamma) in 28 oral carcinoma patients. The patients received daily intravenous injections of rIL-2 (1.2 x 10(5) U/m2) and rIFN-gamma (7.0 x 10(4) U/m2), and both natural killer (NK) and LAK activities were periodically examined. A significant increase in CD16+CD57+ and CD16+CD57- NK subsets was observed after the induction. An increase in the T-cell population was also found, with a significant increase in CD3+HLA-DR+, CD8+Leu8-, and CD4+Leu8- cells. Significant increases in NK activity, from the original level of 32.0 +/- 13.7 to 49.9 +/- 15.2%, and LAK activity, from 4.8 +/- 3.5 to 11.0 +/- 6.1%, at Day 7 were observed. Both activities were maintained at high levels during the cytokine injections, but greater enhancement of the killing activities could not be obtained subsequently. When NK and LAK activities were investigated in each subpopulation of CD3- and CD16- cells, no remarkable cytotoxic activity could be observed before induction in any subset without NK activity in CD3- cells (31.1 +/- 14.3%). At Day 7, NK activity of CD16- cells increased up to 21.4 +/- 14.9%, accompanied by an increase in CD3(-)-cell activity (54.5 +/- 20.6%). LAK activities of both subsets were also enhanced, with activity at Day 7 of 6.5 +/- 5.6 and 9.4 +/- 6.6% in CD16- and CD3- cells, respectively. These increased activities were maintained at the same level during the induction. Phorbol myristate acetate-induced polymorphonuclear leukocyte (PMNL) O2-generation was significantly increased, from the original 81.1 +/- 28.1 to 95.6 +/- 34.9 pmol/min/10(4) cells, after 1 week of treatment. Protein kinase C activity in the cytosol decreased, and the activity in the membrane fraction conversely increased. No remarkable adverse effects except for mild fever were observed. Together with LAK induction ability and PMNL enhancement, with scarce toxicity, a combination of low-dose rIL-2 and rIFN-gamma is thought to be useful in cancer treatments. PMID- 1512304 TI - Why do elderly people seek professional home care? Methodologies compared. AB - In order to investigate which characteristics, besides physical limitations, of elderly people living at home contribute to the utilization of professional home care, a study was conducted in which 450 elderly people aged 55 and over, 123 with and 327 without professional home care, were interviewed. To obtain a selection for the interviews, a postal questionnaire, containing questions on functional status and care utilization, sent out to a random sample of the elderly people (55+) living at home (n = 2451), preceded the actual interviews. The oral interviews yielded the same information, plus an inventory of aspects of the mental status, the social network, the socio-economic status and the housing condition. Analysis was performed in three ways: bivariate analysis, logistic regression analysis and discriminant analysis. The bivariate analysis revealed that users of professional care were older, more often female and more often not married. Their social network was less extensive, as they received less informal care and lived alone more often. Besides they had more mental and financial problems. From the regression analysis it appeared that, in addition to the functional status, the amount of informal care and the household composition contributed to the utilization of professional home care. For the other characteristics inventoried, no independent association with the utilization of professional care could be established. With hindsight, it appeared that in this study long interviews hardly had additional value over postal questionnaires, in which the contribution of functional status and informal care to professional care was already discovered. PMID- 1512303 TI - Altered cytokine production in black patients with keloids. AB - The treatment of keloids in black patients remains a medical dilemma. Previous studies have focused on primary alterations in the metabolism of fibroblasts as the key in the etiology of this condition. Yet alterations in the production of various cytokines which may alter fibroblast responses secondarily have received little attention. Twelve black patients with clinical and histological diagnosis of keloids and eight black control volunteers were studied. Peripheral blood mononuclear-cell (PBMC) fractions from both groups were assayed for production of interleukin-1 (IL-1), interleukin-2 (IL-2), interleukin-6 (IL-6), alpha interferon (IFN-alpha), beta-interferon (IFN-beta), gamma-interferon (IFN-gamma), tumor necrosis factor-alpha (TNF-alpha), and tumor necrosis factor-beta (TNF beta). The production of IFN-alpha, IFN-gamma, and TNF-beta were markedly depressed in keloid patients compared to normal controls. However, IL-1 and IL-2 production was not significantly different between the two groups. In contradistinction, keloid patients produce greater amounts of IL-6, TNF-alpha, and IFN-beta. Altered levels of immunoregulatory cytokines may play a significant role in the net increase in collagen which characterizes keloid formation. PMID- 1512305 TI - Recognition of depression by internal medicine residents. AB - We studied the ability of internal medicine residents to recognize depressive symptoms in a population of lower socio-economic primary care patients. Four hundred twenty patients completed the short form of the Beck Depression Inventory (BDI). Simultaneously, the resident caring for the patient estimated the degree of depression for each patient. One-fourth of the patients scored at or above the moderately depressed level on the BDI and the residents rated 23 percent of their patients as at least moderately depressed. However, the accuracy of the residents' assessment of his or her individual patient was poor (correlation = 0.42, sensitivity = 0.46, specificity = 0.84). Patients with a prior history of psychiatric disorder scored higher on the BDI and were given higher ratings of depression. No other pre-existing medical condition was significantly associated with a higher or lower BDI score. The amount of alcohol consumed and the amount smoked, were both associated with higher BDI scores. Residents varied in their sensitivity to their patients' BDI scores. Some showed high agreement with BDI scores, others low. There were no specific resident characteristics (e.g. year of training, resident gender) that could explain this variability. Patients with a history of depression were given lower resident ratings compared to other patients and patients with a history of depression were given lower resident ratings than predicted by their BDI scores. Residents' ability to accurately diagnose and treat depression in the underprivileged primary care patient can be facilitated by the institution of depression screening in the ambulatory clinic. PMID- 1512306 TI - How sources of health information relate to knowledge and use of cancer screening exams. AB - Utilization of many screening procedures to detect cancer in early stages remains low. In order to design more effective strategies to increase utilization of these tests, we assessed the role and relative importance of different information sources on knowledge and use of cancer screening exams. Where individuals get useful information about disease prevention, and the relationship of information sources to cancer screening knowledge and behavior are reported using data from the 1987 National Health Interview Survey. Results indicate that physicians are perceived as important sources of information on how to prevent illness. However, persons who use print media as their most useful source of information are significantly more likely to have heard of cancer screening procedures than those who rely on the doctor as the source. Those who rely on electronic media tend to be less knowledgeable of all screening procedures examined. A strong and consistent association between doctor as the most useful source of information and actually having received the procedure was found. These results suggest that knowledge may not necessarily be a prerequisite to screening and indicate that reliance on the physician to recommend cancer screening may be critical in utilization of these services. PMID- 1512307 TI - Improving future preventive care through educational efforts at a women's community screening program. AB - Cervical cancer mortality continues to be a significant problem in the United States. Pap Test screening programs have been effective in attracting high risk women, but the impact of these programs on subsequent health care has seldom been explored. This follow up study examined the impact of a cervical cancer screening and education program on preventive health behaviors of New Hampshire women in the 24 months following the screening program. A mailed survey was sent to a random sample of 750 women from program participants to evaluate both their recent preventive health care practices and to identify perceived barriers to obtaining preventive health services. Of these, 71.1 percent responded. Survey responses of the original program participants were linked to each subject's previous answers to the same questions asked 24 months earlier. A comparison group was derived by asking follow up study participants to identify a female acquaintance within five years of her age. Seventy-four percent of the comparison group responded. Survey responses of original program participants were then compared to those of the comparison group. Results indicate that women who participated in the original Project received significantly more preventive health care services in the two years since the Project than in the two years prior to it. Women in the comparison group received more Paps and clinical breast examinations than women in the participant group, perhaps because all participants had received a Pap test two years before. Having a regular health care provider was the most significant characteristic associated with obtaining indicated preventive services. An important contribution of community screening programs may be to encourage women to establish a regular source of care. PMID- 1512308 TI - Dental prosthetic status and needs of an elderly population living in long-term care facilities in Singapore. AB - This study examined the prosthetic status and needs among an elderly population living in long-term care facilities in Singapore. A total of 488 subjects were randomly selected and 479 of them were examined. The results show that 56.2 percent of selected subjects were edentulous while 43.8 percent had one or more teeth missing. The average number of teeth present among dentate subjects was 7.5. Of the edentulous subjects, 78 percent of them reported not having any dentures, and more than 20 percent of existing dentures were found to be defective and had to be replaced. A higher proportion (94 percent) of dentate subjects who could have benefitted from having partial dentures did not have them. The findings of this study clearly demonstrate high unmet needs for prosthetic care among an institutionalized elderly population. PMID- 1512309 TI - Stump the experts. PMID- 1512310 TI - Soft tissue augmentation of periorbital fine lines and the orbital groove with Zyderm-I and fine-gauge needles. AB - A new procedure utilizing Zyderm-I (Collagen Biomedical, Palo Alto, CA) and a 32 gauge needle for augmentation of the periorbital fine lines and the orbital groove is described. This advanced soft tissue augmentation technique is described in detail in 30 patients with before, after, and 1-week post augmentation photographs presented by the author. This technique requires familiarity with soft tissue augmentation and the use of collagen injectable materials as well as specific training on a one-to-one basis with someone experienced with this particular technique. PMID- 1512311 TI - A review of sutures and suturing techniques. AB - The ideal suture is strong, handles easily, and forms secure knots. It causes minimal tissue inflammation and does not promote infection. It stretches and accommodates wound edema. Although no single suture possesses all of these features, proper selection of sutures helps achieve better results in skin surgery. Proper suturing technique is essential for obtaining good cosmetic results and avoiding scarring and poor wound healing. Techniques that must be mastered include good eversion of skin edges, avoiding suture marks, maintaining uniform tensile strength along the skin edges, and precise approximation along skin edges. PMID- 1512312 TI - Extensive scalp lifting. Decrease in complications utilizing unilateral occipital artery ligation and other modifications. AB - The superior yield from extensive scalp lifting has been detracted from by complications, including hemorrhage, scalp necrosis, and the need for greater anesthesia. Intraoperative unilateral occipital artery ligation, with extensive undermining to the nape of the neck on only one side, can minimize the risk of postoperative scalp necrosis or telogen effluvium. Careful hemostasis, extensive infusion of dilute anesthetic, and modifications in instrumentation can decrease the morbidity associated with this procedure. The advantages of the operation include removal of the large amounts of bald scalp, excellent intraoperative visualization, and lack of stretchback and asymmetry. PMID- 1512313 TI - Extensive scalp lifting as a reconstructive tool for a large scalp defect. AB - Extensive scalp lifting is a relatively new technique for the treatment of alopecia. Because this technique involves the undermining of the entire occipitoparietal scalp down to the hairline of the nape, a significant anterior and medial advancement is accomplished with one operation. This case report describes a patient with a large surgically induced scalp defect that was reconstructed with the use of extensive scalp lifting in combination with coronal brow lifting--thus, the intermediate cosmetic deformity of the more commonly used tissue expansion technique was completely circumvented. Why this technique can be substituted for tissue expansion or multiple rotation-transposition flaps in certain cases in elaborated. PMID- 1512314 TI - The purse-string suture in facial reconstruction. AB - Mohs surgical defects in 26 patients were reconstructed utilizing a purse-string suture and a full-thickness graft. The placement of the purse-string suture decreased the surface area of the wound an average of 53%. A full-thickness graft was then placed in the remaining defect. This technique enabled us to repair large wounds of the facial region with a relatively small full-thickness graft. There were no complications in our series. The resultant areas were cosmetically acceptable and resistant to trauma. PMID- 1512315 TI - Q-switched ruby laser treatment of nevus of Ota. AB - Emission of 694-nm laser energy from a Q-switched ruby laser causes photodestruction of cutaneous pigment. The 40-nanosecond pulse duration of Q switched ruby laser light initiates specific damage to melanosomes thus allowing selective treatment of benign pigmented lesions. Nevus of Ota is a benign facial oculocutaneous melanosis that has melanosomes lying deeply within the dermis. We report the successful use of the Q-switched ruby laser in the treatment of two patients with the nevus of Ota. PMID- 1512316 TI - Tissue sparing repair. A new approach to shorten excisional lines. AB - Tissue sparing repair uses primary closure to make a circular or irregular defect into a line. The resultant closure ratio is 1.5:1 without a dog-ear defect for circular closures. Irregular defects will have different closure ratios. Two new suture techniques are used: 1) the horizontal oblique dermal suture, which approximates tissue without undermining and with minimal epidermal wound edge tension; and 2) the apex cutaneous suture, which repairs most dog-ear defects with a suture. Tissue sparing repair may be a useful addition to primary wound closure. PMID- 1512317 TI - An objective quality assessment method for bit-reduction coding of wideband speech. AB - This paper proposes a new objective quality assessment method for bit-reduction coding of wideband speech taking into account the masking effect of quantizing noise. First, this paper analyzes the reliability and sensitivity of the speech quality assessment method, based on a paired-comparison test with a modulated noise reference signal, for the bit-reduction coding of high-quality wideband speech. Then, the perception of quantizing noise is studied using speech with noise synthesized similar to the quantizing noise. The detection of quantizing noise is found to be influenced by masking by the source signal. This leads to a new method of objectively estimating the quality of coding speech by multiple regression analysis. The factors for the estimation are segmental signal-to-noise ratio, spectrum envelope distance between source signal and quantizing noise, and the similarity of the noise power envelope to the source signal in the time domain. This estimation method is applied to the parameter optimization of wideband coding systems. PMID- 1512318 TI - Formant movements of Dutch vowels in a text, read at normal and fast rate. AB - Speaking rate in general, and vowel duration more specifically, is thought to affect the dynamic structure of vowel formant tracks. To test this, a single, professional speaker read a long text at two different speaking rates, fast and normal. The present project investigated the extent to which the first and second formant tracks of eight Dutch vowels varied under the two different speaking rate conditions. A total of 549 pairs of vowel realizations from various contexts were selected for analysis. The formant track shape was assessed on a point-by-point basis, using 16 samples at the same relative positions in the vowels. Differences in speech rate only resulted in a uniform change in F1 frequency. Within each speaking rate, there was only evidence of a weak leveling off of the F1 tracks of the open vowels /a a/ with shorter durations. When considering sentence stress or vowel realizations from a more uniform, alveolar-vowel-alveolar context, these same conclusions were reached. These results indicate a much more active adaptation to speaking rate than implied by the target undershoot model. PMID- 1512319 TI - Production of the word-final English /t/-/d/ contrast by native speakers of English, Mandarin, and Spanish. AB - The primary aim of this study was to determine if adults whose native language permits neither voiced nor voiceless stops to occur in word-final position can master the English word-final /t/-/d/ contrast. Native English-speaking listeners identified the voicing feature in word-final stops produced by talkers in five groups: native speakers of English, experienced and inexperienced native Spanish speakers of English, and experienced and inexperienced native Mandarin speakers of English. Contrary to hypothesis, the experienced second language (L2) learners' stops were not identified significantly better than stops produced by the inexperienced L2 learners; and their stops were correctly identified significantly less often than stops produced by the native English speakers. Acoustic analyses revealed that the native English speakers made vowels significantly longer before /d/ than /t/, produced /t/-final words with a higher F1 offset frequency than /d/-final words, produced more closure voicing in /d/ than /t/, and sustained closure longer for /t/ than /d/. The L2 learners produced the same kinds of acoustic differences between /t/ and /d/, but theirs were usually of significantly smaller magnitude. Taken together, the results suggest that only a few of the 40 L2 learners examined in the present study had mastered the English word-final /t/-/d/ contrast. Several possible explanations for this negative finding are presented. Multiple regression analyses revealed that the native English listeners made perceptual use of the small, albeit significant, vowel duration differences produced in minimal pairs by the nonnative speakers. A significantly stronger correlation existed between vowel duration differences and the listeners' identifications of final stops in minimal pairs when the perceptual judgments were obtained in an "edited" condition (where post-vocalic cues were removed) than in a "full cue" condition. This suggested that listeners may modify their identification of stops based on the availability of acoustic cues. PMID- 1512320 TI - Temporal decline of masking and comodulation masking release. AB - Masking sounds can be continuously present, gated simultaneously with the signal, or gated somewhat prior to the signal. This continuum of relative onset times was explored using waveforms of the sort commonly employed in studies of comodulation masking release (CMR). There was a 50-Hz masker band centered on the 1250-Hz tonal signal, and four 50-Hz flanker bands centered at 850, 1050, 1450, and 1650 Hz. In some conditions, all four flanker bands had the same temporal envelope, and the masker band either had that same envelope (correlated presentations) or a different envelope (uncorrelated presentations). In other conditions, all five bands had different temporal envelopes (all-uncorrelated presentations). The masker band and/or the four flanker bands were either gated nearly simultaneously with the signal (burst conditions) or were gated prior to the signal by a duration that was systematically varied (fringed conditions). The eight listeners could be partitioned into three groups on the basis of their response to these fringing manipulations. Two listeners (the large fringers) showed a gradual improvement in detectability with increasing fringe duration (called a temporal decline of masking), while three others (the small fringers) showed little improvement in detectability. For the remaining three subjects, there was evidence of a "learning" effect that changed them from large fringers to small fringers over a 10-week period of listening. When present, the temporal decline of masking was greater for the correlated than for the uncorrelated comodulation condition; as a consequence, the difference in detectability between them (the comodulation masking release or CMR) increased with fringe duration. By fringing the masker and flanker bands separately and in combination, it was revealed that the temporal declines of masking were primarily attributable to the fringing of the flanker bands. In contrast, large CMRs required long fringes on both the masker and flanker bands. The above results were obtained with 50-ms signals, but generally similar data were obtained with a signal duration of 240 ms. The difficulties raised for experimentalists and theorists by such long-term practice effects are discussed. PMID- 1512321 TI - Sound-power collection by the auditory periphery of the Mongolian gerbil Meriones unguiculatus. I: Middle-ear input impedance. AB - This is the first paper of a series dealing with sound-power collection by the auditory periphery of the gerbil. The purpose of the series is to quantify the physiological action of the gerbil's relatively large tympanic membrane and middle-ear air cavities. To this end the middle-ear input impedance ZT was measured at frequencies between 10 Hz and 18 kHz before and after manipulations of the middle-ear cavity. The frequency dependence of ZT is consistent with that of the middle-ear transfer function computed from extant data. Comparison of the impedance and transfer function suggests a middle-ear transformer ratio of 50 at frequencies below 1 kHz, substantially smaller than the anatomical value of 90 [Lay, J. Morph. 138, 41-120 (1972)]. Below 1 kHz the data suggest a low-frequency acoustic stiffness KT for the middle ear of 970 Pa/mm3 and a stiffness of the middle-ear cavity of 720 Pa/mm3 (middle-ear volume V MEC of 195 mm3); thus the middle-ear air spaces contribute about 70% of the acoustic stiffness of the auditory periphery. Manipulations of a middle-ear model suggest that decreases in V MEC lead to proportionate increases in KT but that further increases in middle ear cavity volume produce only limited decreases in middle-ear stiffness. The data and the model point out that the real part of the middle-ear impedance at frequencies below 100 Hz is determined primarily by losses within the middle-ear cavity. The measured impedance is comparable in magnitude and frequency dependence to the impedance in several larger mammalian species commonly used in auditory research. A comparison of low-frequency stiffness and anatomical dimensions among several species suggests that the large middle-ear cavities in gerbil act to reduce the middle-ear stiffness at low frequencies. A description of sound-power collection by the gerbil ear requires a description of the function of the external ear. PMID- 1512322 TI - Using acoustic distortion products to measure the cochlear amplifier gain on the basilar membrane. AB - Most models of the cochlea developed during the last decade have explained frequency selectivity and sensitivity of the cochlea at threshold by the use of power amplification of the acoustic wave on the basilar membrane. This power amplification has been referred to as the cochlear amplifier (CA). In this paper, a method to measure the cochlear amplifier gain as a function of position along the basilar membrane is derived from a simple model. Next, experimental evidence is presented that strongly restricts the properties of these proposed cochlear amplifier models. Specifically, it is shown that small signals generated by mechanical nonlinearities in the basilar membrane motion are not amplified during basilar membrane propagation, contrary to what would be expected from the cochlear amplifier hypotheses. This paper describes a method of measuring the cochlear power gain as a function of frequency and position, from the stapes to within 2 mm of the place corresponding to the frequency being measured. Experimental results in the cat indicate that the total gain of the cochlear amplifier, over the range of positions measured, must be less than 10 dB. The simplest interpretation of the experimental results is that there is no cochlear amplifier. The results suggest that the cochlea must achieve its frequency selectivity by some other means. PMID- 1512323 TI - Psychometric functions for level discrimination and the effects of signal duration in the goldfish (Carassius auratus): psychophysics and neurophysiology. AB - Classical conditioning of respiration was used to obtain psychometric functions for pulsed tone level discrimination in the goldfish (Carassius auratus). Conditioned respiratory suppression is a graded response that has some properties of a confidence rating measure. These properties were used to obtain receiver operating characteristics (ROC) and psychometric functions using a blocked method of constant stimuli. Empirical ROCs and neurometric functions were also obtained for single auditory-nerve fibers using spike count as the decision variable in order to evaluate a simple rate code for level discrimination. Psychometric and neurometric functions for level discrimination are similar in showing the same general form (summarized by Weibull functions) that is independent of signal duration. The lower slope of neurometric functions compared with behavioral functions for level discrimination is in accord with similar data on sound detection and vision in nonhuman mammals. Both neural and psychophysical level discrimination thresholds decline with increasing duration (20 to 320 ms), with similar slopes except at short signal durations (20 to 50 ms). At these durations, the animal's use of a channel-selection strategy and neural information following stimulus offset could reduce the difference between neural and psychophysical thresholds. The slopes of the neural and psychophysical duration functions are similar to those for human observers, but the majority of auditory-nerve fibers sampled have lower level discrimination thresholds than the behaving animal. Since human observers perform better than the majority of neurons in level discrimination, well-trained human listeners may be able to select channels with superior information, or to combine information across channels in ways that the goldfish and other animals do not. In general, one is encouraged to believe that neural mechanisms need not be more complex or sensitive than those considered here to account for pure-tone level discrimination in fishes, humans, and other vertebrates. PMID- 1512324 TI - Vowel duration in Afrikaans: the influence of postvocalic consonant voicing and syllable structure. AB - A production study was conducted to investigate the effect of vowel lengthening before voiced obstruents, and the possible influence that the openness versus closedness of syllables have on the temporal structure of vowels in some languages. The results revealed that vowels were significantly longer when followed by voiced consonants than voiceless consonants. Vowel duration did not, however, vary with syllable structure. However, vowels in open syllables followed by [+ voiced] consonants tended to be longer than when the following consonants were [- voiced]. These results are discussed in the context of current knowledge of other languages. PMID- 1512325 TI - Preliminary results on speaker-dependent variation in the TIMIT database. AB - A set of phonetic studies based on analysis of the TIMIT speech database is presented. Using a database methodological approach, these studies detail new results in speaker-dependent variation due to sex and dialect region of the talker including effects on stop release frequency, speaking rate, vowel reduction, flapping, and the use of glottal stop. TIMIT was found to be fertile ground for gathering acoustic-phonetic knowledge having relevance to the phonetic classification and recognition goals for which TIMIT was designed, as well as to the linguist attempting to describe regularity and variability in the pronunciation of read English speech. PMID- 1512326 TI - Observations on a principal components analysis of head-related transfer functions. AB - A recent principal components analysis (Kistler and Wightman, 1992) has shown that the transfer functions of the human external ear, for a wide range of source locations, can be expressed as weighted sums of a small number of basis vectors. Directional transfer functions obtained in this laboratory, using substantially different measurement techniques, yielded principal component basis vectors that are remarkably similar to those reported by Kistler and Wightman. When this subject population was divided in half according to the overall physical sizes of subjects, basis vectors computed for the subpopulation of smaller subjects were shifted systematically to higher frequencies relative to those computed for the subpopulation of larger subjects. PMID- 1512328 TI - PAIMS 2: alteplase combined with heparin versus heparin in the treatment of acute pulmonary embolism. Plasminogen activator Italian multicenter study 2. AB - BACKGROUND: The effect of alteplase versus heparin in pulmonary embolism has not been studied extensively with serial pulmonary angiograms. OBJECTIVES: The aim of this randomized, open trial was to evaluate the efficacy and safety of alteplase followed by heparin, versus heparin alone, in 36 patients with angiographically documented pulmonary embolism. METHODS: Twenty patients were allocated randomly to a 2-h infusion of alteplase (10 mg bolus, then 90 mg over 2 h) followed by heparin; the other 16 patients were given intravenous heparin at a continuous infusion rate of 1,750 IU/h. RESULTS: The vascular obstruction, assessed by the Miller index at pulmonary angiography, decreased significantly in alteplase treated patients (p less than 0.01) from a baseline of 28.3 +/- 2.9 to a value of 24.8 +/- 5.2 2 h after the start of infusion; in the heparin group there was no change (from 25.3 +/- 5.3 to 25.2 +/- 5.4). Mean pulmonary artery pressure decreased significantly from a baseline of 30.2 +/- 7.8 mm Hg to 21.4 +/- 6.7 in the alteplase group and increased in the heparin group (from 22.3 +/- 10.5 to 24.8 +/- 11.2 mm Hg). For a subset of patients, lung scans were performed at baseline and on days 7 and 30. There were no differences between the two groups in the follow-up lung scans, but there were significant decreases from the baseline values. Bleeding occurred in 14 of 20 alteplase-treated patients and in 6 of 16 in the heparin group (p = NS). There were three major bleeding episodes in the alteplase group and two in the heparin group. Two patients died after fibrinolysis (one of acute renal failure after cardiac tamponade and one of cardiac arrest after cerebral hemorrhage) and one patient in the heparin group died of recurrent pulmonary embolism. CONCLUSIONS: Alteplase resulted in a greater and faster improvement of the angiographic and hemodynamic variables compared with heparin. However, the high frequency of bleeding observed with alteplase in this trial suggests that patients should be carefully selected before thrombolytic therapy is given. PMID- 1512327 TI - Correlation between level of heparinization and patency of the infarct-related coronary artery after treatment of acute myocardial infarction with alteplase (rt PA). AB - BACKGROUND AND OBJECTIVES: The conjunctive use of intravenous heparin may influence the efficacy of alteplase for coronary thrombolysis in patients with acute myocardial infarction. In this study we examined the relation between the level of intravenous anticoagulation with heparin and sustained coronary artery patency in a subgroup of patients of the European Cooperative Study Group (ECSG) trial. METHODS: In the ECSG trial, patients treated with alteplase and aspirin were randomized to concomitant fixed doses of intravenous heparin (a bolus dose of 5,000 U followed by a continuous infusion of 1,000 U/h or placebo). The current study group comprised 149 of 324 ECSG patients allocated to heparin therapy and 132 of 320 ECSG patients allocated to placebo administration who had both an interpretable coronary angiogram obtained within 6 days of treatment and sufficient plasma samples to assess the level of anticoagulation. Activated partial thromboplastin times, fibrinogen and D-dimer levels were determined on plasma samples at baseline and at 45 min and 3, 12, 24 and 36 h after the start of alteplase administration. RESULTS: The coronary artery patency rate was higher in patients allocated to heparin therapy than in those allocated to placebo (80% and 71%, respectively, p = 0.05). Patients allocated to heparin were classified into three subgroups: 48 patients (32%) with all activated partial thromboplastin times at least twice their own baseline value (optimal anticoagulation), 40 patients (27%) with the lowest activated partial thromboplastin time at 3, 12, 24 or 36 h between 130% and 200% of the baseline value (suboptimal anticoagulation) and 61 patients with at least one activated partial thromboplastin time less than 130% of baseline (inadequate anticoagulation). In the heparin group, coronary artery patency correlated with the level of anticoagulation: 90%, 80% and 72%, respectively, in patients with optimal, suboptimal and inadequate anticoagulation (p = 0.02, optimal vs. inadequate anticoagulation). Heparin administration was associated with a smaller reduction in fibrinogen and a smaller increase in D dimer level during and after alteplase administration. No correlation was found between fibrinogen or D-dimer levels and coronary artery patency. No intracerebral hemorrhage occurred in these patients; however, bleeding was more frequent in the subgroup with optimal anticoagulation (p = 0.05). CONCLUSIONS: Intense anticoagulation with intravenous heparin enhances coronary artery patency after alteplase treatment of acute myocardial infarction. PMID- 1512329 TI - Antiarrhythmic drug therapy and cardiac mortality in atrial fibrillation. The Stroke Prevention in Atrial Fibrillation Investigators. AB - BACKGROUND AND OBJECTIVES: The relation between cardiac mortality and antiarrhythmic drug administration has not been fully determined. This relation was analyzed in 1,330 patients enrolled in the Stroke Prevention in Atrial Fibrillation Study, a randomized clinical trial comparing warfarin, aspirin and placebo for the prevention of ischemic stroke or systemic embolism in patients with nonvalvular atrial fibrillation. METHODS: Patients who received antiarrhythmic drug therapy for atrial fibrillation in this study were compared with patients not receiving antiarrhythmic agents. The relative risk of cardiac mortality, including arrhythmic death, in patients receiving antiarrhythmic drug therapy was determined and adjusted for other cardiac risk factors. RESULTS: In patients receiving antiarrhythmic drug therapy, cardiac mortality was increased 2.5-fold (p = 0.006, 95% confidence interval [CI] 1.3 to 4.9) and arrhythmic death was increased 2.6-fold (p = 0.02, 95% CI 1.2 to 5.6). Among patients with a history of congestive heart failure, those given antiarrhythmic medications had a relative risk of cardiac death of 4.7 (p less than 0.001, 95% CI 1.9 to 11.6) compared with that of patients not so treated; the relative risk of arrhythmic death in the treated group was 3.7 (p = 0.01, 95% CI 1.3 to 10.4). Patients without a history of congestive heart failure had no increased risk of cardiac mortality (relative risk 0.70, 95% CI 0.2 to 3.1) during antiarrhythmic drug therapy. After exclusion of 23 patients with documented ventricular arrhythmias and adjustment for other variables predictive of cardiac death, patients receiving antiarrhythmic drugs were not at increased risk of cardiac death or arrhythmic death. However, in patients with a history of heart failure who received antiarrhythmic drug therapy, the relative risk of cardiac death was 3.3 (p = 0.05, 95% CI 0.99 to 11.1) and that of arrhythmic death was 5.8 (p = 0.009, 95% CI 1.5 to 21.7) compared with the risk in patients not taking antiarrhythmic medications. CONCLUSIONS: Although antiarrhythmic drug therapy was not randomly determined in this trial, the data suggest that in patients with atrial fibrillation and a history of congestive heart failure, the risk of such therapy may outweigh the potential benefit of maintaining sinus rhythm. PMID- 1512330 TI - Incidence and prognostic implications of heart block complicating inferior myocardial infarction treated with thrombolytic therapy: results from TIMI II. AB - OBJECTIVES: The aim of this study was to determine the incidence and significance of second- or third-degree heart block among patients with inferior myocardial infarction treated with thrombolytic therapy. BACKGROUND: Data from the prethrombolytic era suggest that heart block occurs in approximately 20% of patients with acute inferior myocardial infarction and is associated with a marked increase in mortality. Little is known about the incidence and prognostic implications of heart block among patients receiving thrombolytic therapy. METHODS: We studied 1,786 patients with acute inferior myocardial infarction enrolled in the Thrombolysis in Myocardial Infarction (TIMI) II Trial who received recombinant tissue-type plasminogen activator (rt-PA) within 4 h of the onset of symptoms. RESULTS: Heart block occurred in 214 patients (12%); 113 (6.3%) had heart block on presentation and 101 (5.7%) developed heart block in the 24 h after treatment with rt-PA. Patients with heart block at entry were slightly older and a greater proportion had cardiogenic shock. The 21-day mortality rate among patients with heart block at entry was 7.1% (8 of 113), compared with 2.7% (45 of 1,673) among patients without heart block at study entry (relative risk 2.6, p = 0.007). However, heart block was not independently associated with 21-day mortality after adjustment for other variables, including shock. Mortality and other adverse cardiac events in the following year were similar among patients with and without heart block. Among patients without heart block at study entry, coronary angiography among patients randomly assigned to coronary catheterization 18 to 48 h after admission revealed that the infarct related artery was occluded in 28.2% (11 of 39) of patients who developed heart block versus 15.5% (112 of 723) of patients without heart block (p = 0.04). The 21-day mortality rate was increased among patients in whom heart block developed after thrombolytic therapy (9.9% [10 of 101] versus 2.2% [35 of 1,572] of patients without heart block, relative risk 4.5, p less than 0.001). Analysis of the increased mortality among patients who developed heart block suggests that mortality was due to severe cardiac dysfunction; no patient was considered to have died as a result of the heart block or its treatment. CONCLUSIONS: Heart block is common among patients with inferior infarction given thrombolytic therapy and is associated with increased mortality. These clinical and anatomic data provide insight into the mechanism of heart block and increased mortality among such patients. PMID- 1512331 TI - Propafenone-mexiletine combination for the treatment of sustained ventricular tachycardia. AB - OBJECTIVES: The purpose of this study was to explore the efficacy of combined therapy with propafenone and mexiletine for control of sustained ventricular tachycardia. BACKGROUND: Combination antiarrhythmic drug therapy may enhance efficacy and lead to control of ventricular arrhythmias in some patients. Few reports have studied the combination of class IB and class IC drugs. Thus, this study was designed to investigate a combination of mexiletine and propafenone in patients with refractory ventricular tachycardia. METHODS: Sixteen patients with sustained ventricular tachycardia had their clinical arrhythmia induced by programmed stimulation. Procainamide and propafenone alone failed to prevent reinduction of tachycardia in all. Mexiletine was subsequently added to propafenone and programmed stimulation was repeated. RESULTS: With combination therapy ventricular tachycardia was noninducible in three patients (19%). A fourth who had presented with polymorphic ventricular tachycardia had slow bundle branch reentry (cycle length 500 ms) induced. In the other 12, tachycardia cycle length increased from 262 +/- 60 ms at baseline to 350 +/- 82 ms with propafenone and to 390 +/- 80 ms with propafenone plus mexiletine (p less than 0.0001 compared with baseline). Hemodynamic deterioration requiring defibrillation occurred in six patients at baseline study, in five taking propafenone and in two taking both drugs. CONCLUSIONS: The combination of propafenone and mexiletine is effective in suppressing the induction of ventricular tachycardia in some patients refractory to procainamide and propafenone alone. In those in whom ventricular tachycardia could still be induced, the rate was slower and hemodynamically tolerated. PMID- 1512332 TI - Comparison of 24-hour parasympathetic activity in endurance-trained and untrained young men. AB - OBJECTIVES: This study compares 24-h parasympathetic activity in aerobically trained and untrained healthy young men. BACKGROUND: Higher values of parasympathetic nervous system activity are associated with a low mortality rate in patients after myocardial infarction, but it remains uncertain what therapeutic interventions can be used to increase parasympathetic activity. Although it is thought that exercise training can increase parasympathetic activity, studies have reported conflicting results, perhaps because this variable was measured for only brief intervals and usually inferred from changes in reflex responses induced by pharmacologic blockade. METHODS: Parasympathetic activity was assessed noninvasively from 24-h ECG recordings by calculating high frequency (0.15 to 0.40 Hz) beat to beat heart period variability in eight endurance-trained men (maximal oxygen consumption greater than or equal to 55 ml/kg per min) and eight age-matched (mean = 29 yr) untrained men (maximal oxygen consumption less than or equal to 40 ml/kg per min). The data were analyzed separately for sleeping hours when parasympathetic activity is dominant and also for waking hours. RESULTS: The geometric mean of high frequency power was greater in the trained than in the untrained men during the day (852 vs. 177 ms2, p less than 0.005), during the night (1,874 vs. 427 ms2, p less than 0.005) and over the entire 24 h (1,165 vs. 276 ms2, p less than 0.001). CONCLUSIONS: Parasympathetic activity is substantially greater in trained than in untrained men, and this effect is present during both waking and sleeping hours. These data suggest that exercise training may increase parasympathetic activity over the entire day and may therefore prove to be a useful adjunct or alternative to drug therapy in lessening the derangements of autonomic balance found in many cardiovascular diseases. PMID- 1512333 TI - Clinical outcome of patients with advanced coronary artery disease after viability studies with positron emission tomography. AB - OBJECTIVE: The aim of this study was to determine the prognostic significance of perfusion-metabolism imaging in patients undergoing positron emission tomography for myocardial viability assessment. BACKGROUND: Positron emission tomography using nitrogen-13 ammonia and 18fluorodeoxyglucose to assess myocardial blood flow and metabolism has been shown to predict improvement in wall motion after coronary artery revascularization. The prognostic implications of metabolic imaging in patients with advanced coronary artery disease have not been investigated. METHODS: Eighty-two patients with advanced coronary artery disease and impaired left ventricular function underwent positron emission tomographic imaging between August 1988 and March 1990 to assess myocardial viability before coronary artery revascularization. RESULTS: Forty patients underwent successful revascularization. Patients who exhibited evidence of metabolically compromised myocardium by positron emission tomography (decreased blood flow with preserved metabolism) who did not undergo subsequent revascularization were more likely to experience a myocardial infarction, death, cardiac arrest or late revascularization due to development of new symptoms than were the other patient groups (p less than 0.01). Concordantly decreased flow and metabolism in segments of previous infarction did not affect outcome in patients with or without subsequent revascularization. Those with a compromised myocardium who did undergo revascularization were more likely to experience an improvement in functional class than were patients with preoperative positron emission tomographic findings of concordant decrease in flow and metabolism. CONCLUSIONS: Positron emission tomographic myocardial viability imaging appears to identify patients at increased risk of having an adverse cardiac event or death. Patients with impaired left ventricular function and positron emission tomographic evidence for jeopardized myocardium appear to have the most benefit from a revascularization procedure. PMID- 1512334 TI - Does positron emission tomography improve patient selection for coronary revascularization? PMID- 1512335 TI - Functional recovery after coronary revascularization for chronic coronary artery disease is dependent on maintenance of oxidative metabolism. AB - OBJECTIVES: This study was performed to define the importance of maintenance of oxidative metabolism as a descriptor and determinant of functional recovery after revascularization in patients with left ventricular dysfunction attributable to chronic coronary artery disease. BACKGROUND: Although myocardial accumulation of 18F-fluorodeoxyglucose indicates the presence of tissue that is metabolically active, it may not identify those metabolic processes required for restoration of myocardial contractility. Experimental studies suggest that, under conditions of ischemia and reperfusion, maintenance of myocardial oxidative metabolism is an important metabolic determinant of the capacity for functional recovery. METHODS: In 16 patients positron emission tomography was performed to characterize myocardial perfusion (with H(2)15O), oxidative metabolism (with 11C-acetate) and utilization of glucose (with 18F-fluorodeoxyglucose). Dysfunctional but viable myocardium was differentiated from nonviable myocardium on the basis of assessments of regional function before and after coronary revascularization. To define the importance of coronary revascularization on myocardial perfusion and metabolism, tomography was repeated in 11 patients after revascularization. RESULTS: Before revascularization, perfusion in 24 dysfunctional but viable myocardial segments and 29 nonviable segments averaged 79% and 74%, respectively, of that in 42 normal myocardial segments (both p less than 0.01). Dysfunctional but viable myocardium exhibited oxidative metabolism comparable to that in normal myocardium. In contrast, in nonviable myocardium, oxidative metabolism was only 66% of that in normal (p less than 0.01) and 69% of that in reversibly dysfunctional myocardium (p less than 0.003). Regional utilization of glucose normalized to regional perfusion in dysfunctional but viable myocardium was greater than that in normal myocardium (p less than 0.01). However, in both reversibly and persistently dysfunctional myocardium, utilization of glucose normalized to relative perfusion was markedly variable. CONCLUSIONS: The results indicate that preservation of oxidative metabolism is a necessary condition for recovery of function after coronary recanalization in patients with chronic coronary artery disease. Consequently, approaches that measure myocardial oxygen consumption, such as dynamic positron emission tomography with 11C-acetate, should facilitate the identification of those patients most likely to benefit from coronary revascularization. PMID- 1512336 TI - Improved myocardial ischemic response and enhanced collateral circulation with long repetitive coronary occlusion during angioplasty: a prospective study. AB - OBJECTIVES: The goal of the study was to evaluate the progressive increase in ischemic threshold with multiple sequential transient coronary occlusions and to assess the role of the collateral circulation in adaptation to ischemia. BACKGROUND: It has been observed that the duration of balloon inflations during coronary angioplasty can be gradually prolonged during subsequent dilations with a reduction in patient symptoms and diminished ischemic electrocardiographic (ECG) changes. Although the mechanism has not been fully explained, recruitment of coronary collateral circulation induced by repeated coronary occlusion has been reported. The stimuli for recruitment and the natural history of coronary collateral circulation are not understood. METHODS: Seventeen patients with isolated stenosis of the left anterior descending coronary artery and a normal left ventricle were enrolled. Angioplasty consisted of five successive prolonged inflations. Sequential changes in clinical, intracoronary ECG and left ventricular indexes of myocardial ischemia were examined. Coronary collateral channels were evaluated during balloon inflations by ipsilateral and contralateral injections of contrast medium and hemodynamically by occlusion pressure. RESULTS: An improved tolerance to myocardial ischemia with repetitive coronary occlusions was demonstrated by a significant reduction of angina, ST segment deviation, left ventricular filling pressure and less impairment of ejection fraction. Left ventricular wall motion abnormalities remained unchanged. Collateral angiographic grade did not change in 7 patients and increased in 10. CONCLUSIONS: This study confirms a progressive adaptation of myocardial ischemia to repetitive coronary occlusions and supports the concept that sequential episodes of myocardial ischemia are a stimulating factor for the recruitment of collateral channels in humans. These results also suggest that enhancement of recruitable collateral circulation might be an underlying mechanism of myocardial ischemic preconditioning. PMID- 1512337 TI - Effects of converting enzyme inhibition on baroreflex sensitivity in patients with myocardial infarction. AB - BACKGROUND: Baroreflex sensitivity provides useful prognostic information in patients after acute myocardial infarction. However, no data are available about the effects of converting enzyme inhibition on this variable. OBJECTIVES: The aim of the study was to evaluate the effects of angiotensin-converting enzyme inhibition on baroreflex sensitivity in patients after uncomplicated myocardial infarction. METHODS: Twenty-five patients after uncomplicated myocardial infarction underwent baroreflex sensitivity evaluation 72 to 96 h after symptom onset and after 4 days of captopril therapy. Twenty additional patients with the same characteristics were evaluated at the same time intervals before and after placebo administration to identify spontaneous baroreflex sensitivity variations. Baroreflex sensitivity was assessed by calculating the regression line relating phenylephrine-induced increases in systolic blood pressure to the attendant changes in the RR interval. RESULTS: The mean baroreflex sensitivity value increased after captopril administration from 6.5 +/- 4.2 to 11.8 +/- 6.1 ms/mm Hg (p less than 0.01) and in individual analyses increased by greater than 2 ms/mm Hg in 68% of patients. Mean plasma renin activity increased after captopril from 3.7 +/- 2.4 to 8.5 +/- 4.9 ng/ml per h (p less than 0.005). No difference was detectable in baroreflex sensitivity and plasma renin activity values according to the site of necrosis. In the control group, baroreflex sensitivity and plasma renin activity remained unchanged between the two studies. CONCLUSIONS: This study demonstrates that in patients with uncomplicated myocardial infarction, captopril significantly improves the chronotropic response to baroreceptor stimulation. PMID- 1512339 TI - Intraoperative evaluation of mitral valve regurgitation and repair by transesophageal echocardiography: incidence and significance of systolic anterior motion. AB - OBJECTIVE: This study was designed to delineate the utility and results of intraoperative transesophageal echocardiography in the evaluation of patients undergoing mitral valve repair for mitral regurgitation. BACKGROUND: Mitral valve reconstruction offers many advantages over prosthetic valve replacement. Intraoperative assessment of valve competence after repair is vital to the effectiveness of this procedure. METHODS: Intraoperative transesophageal echocardiography was performed in 143 patients undergoing mitral valve repair over a period of 23 months. Before and after repair, the functional morphology of the mitral apparatus was defined by two-dimensional echocardiography; Doppler color flow imaging was used to clarify the mechanism of mitral regurgitation and to semiquantitate its severity. RESULTS: There was significant improvement in the mean mitral regurgitation grade by composite intraoperative transesophageal echocardiography after valve repair (3.6 +/- 0.8 to 0.7 +/- 0.7; p less than 0.00001). Excellent results from initial repair with grade less than or equal to 1 residual mitral regurgitation were observed in 88.1% of patients. Significant residual mitral regurgitation (grade greater than or equal to 3) was identified in 11 patients (7.7%); 5 underwent prosthetic valve replacement, 5 had revision of the initial repair and 1 patient had observation only. Of the 100 patients with a myxomatous mitral valve, the risk of grade greater than or equal to 3 mitral regurgitation after initial repair was 1.7% in patients with isolated posterior leaflet disease compared with 22.5% in patients with anterior or bileaflet disease. Severe systolic anterior motion of the mitral apparatus causing grade 2 to 4 mitral regurgitation was present in 13 patients (9.1%) after cardiopulmonary bypass. In 8 patients (5.6%), systolic anterior motion resolved immediately with correction of hyperdynamic hemodynamic status, resulting in grade less than or equal to 1 residual mitral regurgitation without further operative intervention. Transthoracic echocardiography before hospital discharge demonstrated grade less than or equal to 1 residual mitral regurgitation in 86.4% of 132 patients studied. A significant discrepancy (greater than 1 grade) in residual mitral regurgitation by predischarge transthoracic versus intraoperative transesophageal echocardiography was noted in 17 patients (12.9%). CONCLUSIONS: Transesophageal echocardiography is a valuable adjunct in the intraoperative assessment of mitral valve repair. PMID- 1512338 TI - Prospective analysis of possible myocardial damage or hemolysis occurring as a result of prolonged autoperfusion angioplasty in humans. AB - OBJECTIVES: The purpose of this study was to further explore the procedural safety of prolonged (15-min) dilation using an autoperfusion coronary angioplasty balloon by assessing the degree of myocardial damage or hemolysis, if any, occurring as a result of the procedure. BACKGROUND: Prolonged balloon inflation periods may be beneficial during percutaneous transluminal coronary angioplasty. The duration of standard balloon angioplasty is often limited by the occurrence of myocardial ischemia due to loss of anterograde blood flow. Autoperfusion angioplasty allows continued myocardial perfusion during balloon inflation and has previously been shown to reduce but not totally eliminate acute myocardial ischemia during prolonged (up to 15 min) balloon inflation. The risk of intravascular hemolysis as a result of autoperfusion angioplasty has not yet been fully delineated. METHODS: Sixty-two consecutive patients (76% men; mean age 58 years) undergoing elective percutaneous transluminal coronary angioplasty of a single lesion were studied. Serial electrocardiographic and creatine kinase MB isoenzyme data were examined to detect evidence of myocardial damage. Tests for hemolysis (plasma free hemoglobin, serum haptoglobin and serum lactate dehydrogenase) were obtained in the 1st 24 consecutive patients. RESULTS: Inflation time was 14 +/- 4 min (mean +/- SD) and the procedure was successful (less than or equal to 50% residual lesion stenosis) in 59 patients (95%). Electrocardiographic evidence of myocardial infarction (greater than 1 mm persistent ST segment depression, greater than 1 mm ST segment elevation or new Q waves) was not observed in any patient. Cardiac enzyme assays were within the normal range in all patients. No evidence of hemolysis was found in the 24 consecutive patients studied. CONCLUSIONS: We conclude that prolonged autoperfusion angioplasty can be performed in patients without clinical evidence of myocardial damage or hemolysis. PMID- 1512340 TI - Nonsurgical closure of femoral pseudoaneurysms complicating cardiac catheterization and percutaneous transluminal coronary angioplasty. AB - OBJECTIVES: This study was performed to describe the initial experience and follow-up of ultrasound-guided compression of pseudoaneurysms in patients receiving systemic anticoagulant or antiplatelet therapy, or both, after recent cardiac catheterization or percutaneous transluminal coronary angioplasty. BACKGROUND: Femoral artery pseudoaneurysm formation after an interventional procedure is becoming more common as larger caliber catheters and prolonged anticoagulant and antiplatelet therapy are being used. Traditional treatment of this complication has been surgical repair. This study describes a new method of closing femoral pseudoaneurysms by using external compression guided by Doppler color flow imaging. METHODS: Fifteen patients, 3 undergoing cardiac catheterization and 12 undergoing coronary angioplasty, developed an expansile groin mass at the vascular access site diagnosed as a femoral artery pseudoaneurysm by Doppler ultrasound. Seven of the patients had undergone coronary stenting and were receiving postprocedural anticoagulant therapy. These patients underwent progressive graded mechanical (C-clamp) external compression guided by ultrasound. The mechanical compression was titrated to obliterate the vascular tracts to these aneurysms and maintain adequate flow in the femoral artery. RESULTS: After an average compression time of 30 min (range 10 to 120), these tracts remained closed. Follow-up ultrasound examination at 24 h or later confirmed continued closure in all. CONCLUSIONS: This study suggests that nonsurgical closure of femoral pseudoaneurysms is feasible. This technique may be valuable in managing vascular access-related complications after diagnostic and interventional procedures, even in patients requiring prolonged anticoagulant therapy. PMID- 1512341 TI - Effects of diuretic therapy on the development of tolerance during continuous therapy with nitroglycerin. AB - OBJECTIVES: This study examined the effects of concurrent diuretic therapy on the hemodynamic responses to short-term and sustained therapy with transdermal nitroglycerin. BACKGROUND: Sodium retention and plasma volume expansion occur during therapy with nitroglycerin and may play a role in the loss of nitroglycerin effects during sustained therapy. METHODS: Twenty-two normal male volunteers were treated for 1 week with either hydrochlorothiazide and amiloride (50 + 5 mg) (n = 11) or placebo (n = 11) in a randomized, double-blind fashion. All 22 subjects then received continuous transdermal nitroglycerin (19 +/- 1 mg/24 h) for 5 to 7 days. RESULTS: On the first and last day of transdermal nitroglycerin therapy, standing heart rate, systolic blood pressure and hematocrit values were assessed at 8, 9 and 10 AM and 12 noon. Heart rate and blood pressure responses to sublingual nitroglycerin (0.6 mg) were also evaluated before and after sustained transdermal nitroglycerin therapy. A significant loss of the hemodynamic effects of transdermal and sublingual nitroglycerin occurred during sustained therapy in both the diuretic and placebo therapy groups. In both groups, transdermal nitroglycerin therapy was associated with a significant decrease in hematocrit that persisted for the entire treatment period. CONCLUSIONS: These results suggest that diuretic therapy does not prevent plasma volume expansion or the loss of hemodynamic effects during sustained transdermal nitroglycerin therapy. The persistent decrease in hematocrit suggests that plasma volume expansion plays a role in the attenuation of nitrate effects. It also provides evidence of continued vascular activity of nitroglycerin despite loss of systemic hemodynamic effects. PMID- 1512342 TI - Restenosis after directional coronary atherectomy. AB - OBJECTIVES: This study evaluates the incidence of restenosis after successful directional coronary atherectomy and identifies risk factors for restenosis. BACKGROUND: Directional coronary atherectomy has been shown to be a safe and effective treatment of obstructive coronary artery disease; however, information regarding restenosis is limited. METHODS: Between October 1986 and December 1989, 289 patients with 332 lesions were successfully treated with directional coronary atherectomy and followed up prospectively. Clinical follow-up information was available for 98% and angiographic follow-up information was obtained for 82% at approximately 6 months, or earlier if symptoms recurred. Angiograms were quantitatively analyzed. Restenosis was defined as greater than 50% stenosis at the site of intervention. RESULTS: Seventy-four percent of patients were either asymptomatic or clinically improved after the procedure. Thirty-two percent were subsequently treated by coronary artery bypass surgery (14%), percutaneous transluminal coronary angioplasty (4%) or repeat atherectomy (13%). Angiographic evidence of restenosis was observed in 42%. The restenosis rate in native coronary arteries was 31% for primary lesions and 28% and 49%, respectively, for lesions treated with one or two previous angioplasty procedures. The restenosis rate for saphenous vein grafts was 53% for primary lesions and 58% and 82%, respectively, for lesions treated with one or two previous angioplasty procedures. The median interval to angiographically documented restenosis was 133 days. A higher restenosis rate was associated with a saphenous vein graft, hypertension, a longer lesion (greater than or equal to 10 mm), a smaller vessel diameter (less than 3 mm), a noncalcified lesion and use of a smaller (6F) device. CONCLUSIONS: Restenosis remains a limitation of directional coronary atherectomy. A subset of patients with larger vessels, shorter lesions or lesions treated with a larger (7F) device may have a more favorable outcome. PMID- 1512343 TI - Natural history of sinus node disease treated with atrial pacing in 213 patients: implications for selection of stimulation mode. AB - OBJECTIVES: This study was designed to analyze the incidence and determinants of complications and long-term survival in sinus node disease treated with atrial pacing. BACKGROUND: Knowledge of the natural history of sinus node disease treated with different pacing modes is imperfect, and controversy exists regarding the optimal pacemaker therapy. METHODS: A consecutive series of 213 patients with sinus node disease initially treated with atrial pacing was studied for a median follow-up period of 60 months. The end points studied were permanent atrial fibrillation, high grade atrioventricular (AV) block, P wave undersensing, pacing mode change, reoperation and death. Several prognostic factors were evaluated statistically and the survival rate was compared with that of a matched general population. RESULTS: The incidence rate of permanent atrial fibrillation during follow-up was 7% (1.4%/year). The risk of this arrhythmia increased substantially with age greater than or equal to 70 years at pacemaker implantation. Only 2 of the 15 patients who developed permanent atrial fibrillation required ventricular pacing. High grade AV block occurred in 8.5% (1.8%/year) and its incidence was much greater in patients with complete bundle branch block or bifascicular block (35%) than in patients without such conduction disturbances (6%). A change to ventricular or dual-chamber stimulation was necessary in 14% of all patients, primarily because of early lead dislodgment or high grade AV block. Surgical intervention with maintenance of atrial pacing was required in 7% of patients. The survival rates of 97% at 1 year, 89% at 5 years and 72% at 10 years did not differ significantly from those of a matched general population. CONCLUSIONS: In sinus node disease, atrial pacing can be successfully applied during long-term follow-up. Patients with complete bundle branch or bifascicular block in addition to sinus node disease should initially receive a dual-chamber pacemaker, but routine application of dual-chamber stimulation does not appear to be warranted. PMID- 1512344 TI - Sudden cardiac death associated with isolated congenital coronary artery anomalies. AB - OBJECTIVES AND BACKGROUND: Congenital coronary anomalies are associated with sudden death and exercise-related death. Clarification of the risk and mechanisms of sudden death in patients with coronary anomalies may aid in decisions on intervention. METHODS: The clinicopathologic records of 242 patients with isolated coronary artery anomalies were reviewed for information on mode of death and abnormalities of the initial segment (acute angle takeoff, valvelike ridges or aortic intramural segments) and course of the anomalous coronary artery. RESULTS: Cardiac death occurred in 142 patients (59%); 78 (32%) of these deaths occurred suddenly. Of sudden deaths, 45% occurred with exercise. Sudden death (28 of 49, 57%) and exercise-related death (18 of 28, 64%) were most common with origin of the left main coronary artery from the right coronary sinus. Anomalous origin of the right coronary artery from the left coronary sinus was also commonly associated with exercise-related sudden death (6 of 13 sudden deaths, 46%). High risk anatomy involved abnormalities of the initial coronary artery segment or coursing of the anomalous artery between the pulmonary artery and aorta. Younger patients (less than or equal to 30 years old) were significantly more likely than older patients (greater than or equal to 30 years old) to die suddenly (62% vs. 12%, p = 0.0001) or during exercise (40% vs. 2%, p = 0.00001) despite their low frequency of significant atherosclerotic coronary artery disease (1% vs. 40%, p = 0.00001). CONCLUSIONS: Younger patients (less than or equal to 30 years old) with an isolated coronary artery anomaly are at risk of dying suddenly and with exercise. Therefore, greater effort for early detection and surgical repair of these lesions is warranted. PMID- 1512345 TI - Ventricular tachycardia after surgical repair of tetralogy of Fallot: results of intraoperative mapping studies. AB - OBJECTIVES: Four patients with previous repair of tetralogy of Fallot and ventricular tachycardia underwent map-guided surgery to ablate the arrhythmias. BACKGROUND: Although patients with repaired tetralogy of Fallot are at increased risk of sudden death due to ventricular tachycardia, little is known of the origin and mechanism of this arrhythmia. METHODS: A customized right ventricular balloon with 112 electrodes was used to record endocardial activation and, where possible, simultaneous epicardial recordings were obtained with a sock electrode array. Three patients had an aneurysm of the right ventricular outflow tract and one had a septal aneurysm. All had moderate to severe pulmonary valve insufficiency. Preoperative electrophysiologic study demonstrated inducible rapid (cycle length 180 to 300 ms) hemodynamically unstable monoform ventricular tachycardias. RESULTS: Intraoperatively, five different tachycardias (two in one patient) were induced and mapped. The sites of earliest activation were located in the subendocardium of the right ventricular outflow tract in all, but they varied widely among the septum, free wall and parietal band and could not be identified by visible scar. All were due to a macroreentrant circuit initiated by a critical delay in activation beyond a functional arc of block. Two patients treated by cryoablation while the heart was beating and perfused at normal temperature had inducible ventricular tachycardia postoperatively. In the two subsequent patients, the application of cryoablation under anoxic cardiac arrest resulted in noninducibility of arrhythmia. CONCLUSIONS: Ventricular tachycardia in tetralogy of Fallot in these four patients was caused by macroreentry in the right ventricular outflow tract. Surgical success depends on detailed mapping and cryoablation under anoxic cardiac arrest. In patients at risk of sudden death, map-directed surgery may offer distinct advantages over either implantable devices or drug therapy. PMID- 1512346 TI - Characteristics of local electrogram predicting successful transcatheter radiofrequency ablation of left-sided accessory pathways. AB - OBJECTIVES: The purpose of this study was to analyze and compare the local electrograms recorded at successful and unsuccessful sites of ablation to identify the criteria that may predict successful sites and minimize unnecessary radiofrequency delivery. BACKGROUND: Transcatheter ablation of accessory pathways using radiofrequency energy requires extremely precise localization of an accessory pathway. METHODS: Local electrograms from 50 consecutive patients with left-sided accessory pathways who underwent transcatheter radiofrequency ablation were analyzed. During catheter ablation, localization of accessory pathways was performed in 39 pathways during pre-excited sinus rhythm and in 14 pathways during orthodromic tachycardia. A total of 429 local electrograms at target sites obtained before delivery of radiofrequency current was analyzed. A prospective study was performed in another 20 patients using the criteria derived from the retrospective study. RESULTS: Accessory pathway conduction block was achieved in 36 (92%) of 39 pathways in which mapping was performed during pre-excited sinus rhythm and in 9 (64%) of 14 pathways in which mapping was performed during orthodromic tachycardia (p less than 0.05). When mapping was performed during pre excited sinus rhythm, a combination of four variables (that is, an accessory pathway potential, stability of local electrograms, atrial activation greater than 1 mV and ventricular activation preceding the onset of the delta wave) showed a 62% probability of success. In contrast, excluding these variables resulted in a 95% probability of failure (noneffective or transiently effective). The prospective study shows that the use of these criteria can significantly reduce the number of current applications. When mapping was performed during orthodromic tachycardia, recording the earliest atrial activation was the most powerful predictor of success. A stable local electrogram with a small notch on the ventricular potential, presumed to be an accessory pathway potential, may add predictive value. CONCLUSIONS: Transcatheter radiofrequency ablation is highly effective in the treatment of patients with left-sided accessory pathways. Specific characteristics of local electrograms can be important predictors of success or failure. Mapping during pre-excited rhythm renders ablation more effective than does mapping during orthodromic tachycardia. PMID- 1512347 TI - Clinical characteristics and electrophysiologic properties of atrioventricular accessory pathways: importance of the accessory pathway location. AB - OBJECTIVES: This study was designed to assess the influence of accessory atrioventricular (AV) pathway location on the clinical and electrophysiologic characteristics of 384 consecutive symptomatic patients having a single accessory pathway. METHODS: Four locations were studied: left free wall (n = 270), posteroseptal (n = 52), anteroseptal (n = 29) and right free wall (n = 33). Ten clinical variables and 12 electrophysiologic variables were analyzed, including the effective refractory period of the accessory pathway and the different clinically occurring and inducible arrhythmias. RESULTS: Only two clinical findings were associated with accessory pathway location: 1) later age at onset of symptoms in the left free wall versus other accessory pathway locations (24 +/ 12 vs. 20 +/- 11 years, p = 0.02), and 2) later age at the time of electrophysiologic study in the left free wall accessory pathway location (36 +/- 13 vs. 32 +/- 11 years, p = 0.01). Six electrophysiologic variables showed a correlation with the accessory pathway location: 1) retrograde conduction only was found less frequently in right free wall (9%) and anteroseptal (10%) than in left free wall (26%) and posteroseptal (29%) accessory pathway locations (p = 0.05); 2) the retrograde effective refractory period of the accessory pathway was shorter in anteroseptal (253 +/- 52 ms) and left free wall (270 +/- 72 ms) as compared with right free wall (296 +/- 101 ms) and posteroseptal (301 +/- 76 ms) locations (p = 0.05); 3) retrograde decremental conduction over the accessory pathway was present in the posteroseptal (17%) and left free wall (3%) but absent in the other locations (p less than 0.001); 4) anterograde decremental conduction was only seen in the right free wall location (12%) (p less than 0.001); 5) orthodromic reentrant tachycardia was induced less frequently in the right free wall than in other locations (70% vs. 93%, p less than 0.001); and 6) inducibility of atrial fibrillation was greater in anteroseptal (62%) than in right free wall (21%), left free wall (44%) and posteroseptal (36%) locations (p = 0.01). CONCLUSIONS: The location of the accessory AV pathway is associated with specific electrophysiologic characteristics. PMID- 1512348 TI - Parathyroid hormone responses to marked hypocalcemia in infants and young children undergoing repair of congenital heart disease. AB - OBJECTIVES: The integrity of the parathyroid axis was tested in 18 infants and young children undergoing repair of congenital heart disease with cardiopulmonary bypass. BACKGROUND: Infants are believed to have an immature parathyroid hormone response to hypocalcemia. Whereas adults are known to respond appropriately to hypocalcemia during cardiopulmonary bypass, children have not been studied carefully. METHODS: Calcium, magnesium, parathyroid hormone, phosphate and total protein were measured in blood samples withdrawn at defined times before, during and after cardiopulmonary bypass. RESULTS: At the initiation of cardiopulmonary bypass, ionized calcium decreased markedly in 12 infants less than or equal to 24 months old (mean +/- SEM 1.11 +/- 0.04 to 0.29 +/- 0.05 mM) and decreased significantly in 6 young children greater than 24 months old (1.19 +/- 0.02 to 0.42 +/- 0.12 mM). In response to hypocalcemia, parathyroid hormone concentration increased significantly in both the infants (from 42 +/- 8 to 103 +/- 29 and 85 +/- 22 pg/ml) and the young children (from 39 +/- 8 to 44 +/- 20 and 92 +/- 30 pg/ml). Before separation from cardiopulmonary bypass, increased parathyroid hormone concentration restored ionized calcium concentration to 0.75 +/- 0.03 mM in the infants and to 0.92 +/- 0.07 mM in the young children. There was no significant influence of either age or the use of deep hypothermia and circulatory arrest on either calcium or parathyroid hormone responses. Total magnesium and total protein concentrations decreased on initiation of cardiopulmonary bypass and thereafter remained stable. Phosphate concentrations were unchanged during the study. CONCLUSIONS: In infants and young children undergoing cardiac surgery, the parathyroid hormone response to both hypocalcemia and to rising ionized calcium concentrations was at least as great as that of adults. Thus, the calcium-parathyroid-vitamin D axis functions in infants and young children as it does in adults. PMID- 1512349 TI - Mechanisms of balloon angioplasty and directional coronary atherectomy as assessed by intracoronary ultrasound. AB - OBJECTIVE: This study was designed to use intracoronary ultrasound imaging to elucidate the physical effects of balloon angioplasty and directional coronary atherectomy in vivo in humans. BACKGROUND: The proposed mechanisms of coronary artery interventions such as balloon angioplasty and directional atherectomy are based on animal studies or pathologic findings and these data may not be applicable to living patients. Intracoronary ultrasound findings correlate highly with pathologic results and may allow in vivo assessment of the mechanisms of such interventions in humans. METHODS: Intracoronary ultrasound imaging was performed in 45 patients after a successful coronary intervention (balloon angioplasty in 30, directional coronary atherectomy in 15). Ultrasound images obtained at the treatment site and at an adjacent angiographically normal references site were analyzed quantitatively for minimal lumen diameter, cross sectional lumen area, are enclosed by the internal elastic lamina, plaque area (internal elastic lamina area--lumen area) and percent area stenosis (plaque area/internal elastic lamina area). Qualitative analysis included assessment of presence of dissection, plaque composition and plaque topography. RESULTS: The results of the two procedures were similar with respect to minimal lumen diameter (angioplasty 2.6 +/- 0.5 vs. atherectomy 2.6 +/- 0.3 mm, p = NS), lumen area (0.07 +/- 0.03 vs. 0.07 +/- 0.02 cm2, p = NS) and percent area stenosis (59 +/- 14% vs. 51 +/- 21%, p = NS). However, after angioplasty, the internal elastic lamina area was significantly larger at the treated site than at the reference site (delta = +0.03 +/- 0.04 cm2, p = 0.01). There was no significant difference between the two sites after atherectomy (delta = -0.01 +/- 0.05 cm2, p = NS). In addition, dissection was seen significantly more often after balloon angioplasty than after atherectomy (50% vs. 7%, p less than 0.01). The results were similar when stratified for plaque composition and morphology. These data were confirmed in six additional patients who underwent ultrasound imaging before and after the intervention. CONCLUSIONS: Thus, the improvement in lumen dimensions after coronary balloon angioplasty is a result of both vessel stretch, demonstrated by a larger internal elastic lamina area at the treated site, and dissection. Both vessel stretch and dissection are uncommon after atherectomy, a finding consistent with plaque removal as the major mechanism for improved lumen area after this procedure. PMID- 1512350 TI - In vitro validation of three-dimensional intravascular ultrasound for the evaluation of arterial injury after balloon angioplasty. AB - OBJECTIVES: The hypothesis of this study was that three-dimensional ultrasound imaging would facilitate the evaluation of arterial dissection after balloon angioplasty. BACKGROUND: The presence and extent of arterial dissection occurring at the time of balloon angioplasty may be important predictors of abrupt vessel closure or late restenosis. METHODS: Forty-one human arterial segments obtained after death were imaged in an in vitro system at physiologic pressure (80 to 100 mm Hg) before and after balloon angioplasty. Images were acquired with a 20- to 30-MHz mechanical intravascular ultrasound imaging system (Cardiovascular Imaging Systems) with a constant pullback technique (1 mm/s). Standard 0.5-in. (1.27-cm) video tapes were used for data storage and later playback for analog to digital conversion. Digitized data were reconstructed to three-dimensional images with use of voxel space modeling. The vessels were opened longitudinally and subjected to pathologic examination, photographed and classified histologically as normal, fibrous or calcified. Dissection was defined as a disruption and separation of components of the arterial wall. The length and depth of arterial dissection were evaluated grossly and microscopically. RESULTS: Of the 41 arteries studied, 36 (88%) exhibited dissection on pathologic examination after balloon angioplasty. Three-dimensional reconstruction of intravascular ultrasound images identified dissection in 11 (92%) of 12 normal, 8 (100%) of 8 fibrous and 11 (69%) of 16 calcified arteries. Excellent agreement between ultrasound and pathologic findings was achieved in the evaluation of length and depth of dissection for histologically normal and fibrous arteries (kappa = 0.72 to 1.0). When the vessels were severely calcified, the agreement was not as good (kappa = 0.27 to 0.56), particularly in detection of small, non-raised intimal flaps. CONCLUSIONS: This histopathologic validation study suggests that three-dimensional intravascular ultrasound imaging facilitates the evaluation of both quantitative and morphologic features of arterial dissection induced by balloon angioplasty. The advantage of three-dimensional intravascular ultrasound is its ability to assess the length and morphology of arterial injury over an entire vessel segment. PMID- 1512351 TI - Coronary balloon angioplasty dissections: "the good, the bad and the ugly". PMID- 1512352 TI - Low energy conversion of atrial fibrillation in the sheep. AB - OBJECTIVES: In this study, the feasibility, efficacy and safety of low energy internal atrial cardioversion were investigated in a sheep model. The relation between the level of energy used for atrial defibrillation and the probability of successful cardioversion was examined. BACKGROUND: Atrial fibrillation is a common clinical arrhythmia that frequently recurs after termination with high energy external cardioversion. In some patients with drug-refractory and poorly tolerated atrial fibrillation, an automatic implantable cardioverter may prove useful by providing rapid restoration of sinus rhythm. METHODS: In 16 pentobarbital-anesthetized sheep, a right atrial spring electrode was implanted percutaneously and a left thoracic cutaneous patch electrode was placed on the thorax. Sustained atrial fibrillation was induced by rapid atrial pacing and terminated by biphasic cathodal shocks synchronized to the R wave of the surface electrocardiogram (ECG). RESULTS: During 768 defibrillation attempts in 16 sheep, the percent of successful cardioversion attempts increased in a dose-response manner, reaching a plateau at the average energy level of 5 J. With greater than or equal to 1.5 and greater than or equal to 2.5 J energy levels, cardioversion was achieved, respectively, in greater than 50% and greater than 80% of attempts. Ventricular fibrillation occurred in 18 (2.4%) of 768 cardioversion attempts; in all 18 cases, the shock was poorly synchronized with the ECG R wave. CONCLUSIONS: Low energy cardioversion of atrial fibrillation to sinus rhythm is feasible with use of a right atrial spring/cutaneous patch electrode configuration. The percent of successful cardioversion attempts depends on the level of energy output, and there is a risk of ventricular fibrillation if cardioversion is poorly synchronized with ventricular depolarization. PMID- 1512353 TI - The relationship between myocardial retention of technetium-99m teboroxime and myocardial blood flow. AB - OBJECTIVES: The aim of this study was to define the temporal changes in the relationship between technetium-99m teboroxime tissue retention and myocardial blood flow in a canine model. BACKGROUND: Technetium-99m teboroxime is a new neutral lipophilic myocardial perfusion agent. It is known to be highly extracted by the myocardium but to have a rapid clearance rate. METHODS: A wide range of myocardial blood flow was induced in each experiment by regional coronary occlusion and dipyridamole infusion. Myocardial retention of technetium-99m teboroxime was determined by in vitro tissue counting at 1, 2 or 5 min after injection of the tracer. Tracer retention was correlated with microsphere determined blood flow and the data were fitted to nonlinear functions. RESULTS: Correlation coefficients for these functions were 0.92, 0.95 and 0.95 at 1, 2, and 5 min, respectively. At 1 min after injection, the relationship of technetium 99m teboroxime retention to blood flow was linear over a wide flow range, becoming nonlinear at flow rates greater than 4.5 ml/min per g. After 5 min the retention-flow relationship was linear only to 2.5 ml/min per g, above which little change in retention was noted. Normalized myocardial retention, expressed as a percent of the retention at 1 ml/min per g, was also calculated. At flow rates of 1, 2, 3, 4 and 5 ml/min per g, normalized retention was 100, 169, 228, 277 and 317% at 1 min and 100, 171, 217, 239 and 237% at 5 min after injection. CONCLUSIONS: At 1 min after injection, the relationship of technetium-99m teboroxime myocardial retention to blood flow is well maintained over a wide range of flow. However, after only 5 min, tracer retention underestimates flow changes at moderate and high flow rates. Thus, rapid acquisition protocols are necessary to fully exploit the potential of this promising new tracer in the evaluation of myocardial perfusion. PMID- 1512354 TI - Noninvasive evaluation of myocardial perfusion with use of technetium-99m teboroxime. PMID- 1512355 TI - Functional impact of remodeling during healing after non-Q wave versus Q wave anterior myocardial infarction in the dog. AB - OBJECTIVES: This study was undertaken to compare changes in left ventricular remodeling and function during healing after a first anterior non-Q wave versus a Q wave myocardial infarction in the dog. BACKGROUND: Whether ventricular remodeling is more severe after anterior Q wave than after anterior non-Q wave infarction has not been studied systematically. METHODS: Serial remodeling and functional variables (two-dimensional echocardiography), electrocardiography and hemodynamic data were recorded over 6 weeks in 58 instrumented dogs subjected to left anterior descending coronary artery ligation or ligation plus collateral obliteration. Postmortem topography and transmurality (by planimetry) and infarct collagen (hydroxyproline) were measured at 6 weeks. RESULTS: At 6 weeks, infarct collagen was similarly increased in both groups, but the Q wave group had greater infarct size (7.2% vs. 4.5%, p less than 0.025) and greater transmurality (88% vs. 58%, p less than 0.001), higher left atrial pressures, more infarct expansion (expansion index 2.62 vs. 2.31, p less than 0.001), more thinning (thinning ratio 0.62 vs. 0.72, p less than 0.001), greater cavity dilation (diastolic volume 88 vs. 72 ml, p less than 0.001), more regional bulging in the short-axis view (depth 4.9 vs. 1.9 mm, p less than 0.001), more regional asynergy (18% vs. 7%, p less than 0.001), lower global ejection fraction (40% vs. 48%, p less than 0.001), more endocardial and epicardial bulging in the long-axis view and greater incidence of aneurysm (82% vs. 36%, p less than 0.005), left ventricular thrombus (64% vs. 0%, p less than 0.0005) and ventricular arrhythmias. Echocardiograms obtained during a 6-week period indicated that left ventricular topographic deterioration and dysfunction were present in the earliest postinfarction study at 2 days in both groups but were more frequent in the Q wave group. Regional myocardial blood flow (24 dogs) was lower in the Q wave than in the non-Q wave group. Scanning electron microscopy (10 dogs) revealed preservation of the epicardial collagen matrix in the non-Q wave but not the Q wave group. CONCLUSIONS: Anterior Q wave infarction is associated with greater transmurality and more postinfarction left ventricular remodeling and dysfunction than is non-Q wave infarction. PMID- 1512356 TI - Clinical demonstration that catheter-delivered ultrasound energy reverses arterial vasoconstriction. AB - OBJECTIVES: This study was designed to describe the clinical effects of ultrasound energy on guide-wire-induced arterial vasoconstriction. BACKGROUND: We have previously shown that ultrasound energy (20 kHz) delivered by a wire probe produces dose-dependent, endothelium-independent smooth muscle relaxation capable of reversing both receptor-mediated and voltage-dependent vasoconstriction in vitro. METHODS: A high intensity, low frequency ultrasound catheter system was used to recanalize total occlusions in the superficial femoral arteries of two patients. After recanalization, the proximal residual stenoses were each less than 15%. However, distal arterial vasospasm was found angiographically in a popliteal artery of one patient and in an anterior tibial artery of another. Subsequently, the ultrasound catheter probe was advanced to the sites of arterial vasospasm (diffuse in one, focal in one). RESULTS: After 30 and 90 s, respectively, of exposure to ultrasound energy with a frequency of 19.5 kHz, peak tip amplitude of 111 microns and power output at the transducer of 25 W, the vasospasm resolved in each arterial segment. CONCLUSIONS: Our findings are the first reported clinical cases documenting that catheter-delivered low frequency, high intensity ultrasound induces arterial vasodilation at the site of vasoconstriction. These biologic effects appear to be relatively unique for an angioplasty device and may have potential clinical importance. PMID- 1512357 TI - Acute myocardial infarction in the diabetic patient: pathophysiology, clinical course and prognosis. AB - Although there have been significant advances in the care of many of the extrapancreatic manifestations of diabetes, acute myocardial infarction continues to be a major cause of morbidity and mortality in diabetic patients. Factors unique to diabetes increase atherosclerotic plaque formation and thrombosis, thereby contributing to myocardial infarction. Autonomic neuropathy may predispose to infarction and result in atypical presenting symptoms in the diabetic patient, making diagnosis difficult and delaying treatment. The clinical course of myocardial infarction is frequently complicated and carries a higher mortality rate in the diabetic than in the nondiabetic patient. Although the course and pathophysiology of myocardial infarction differ to some degree in diabetic patients from those in patients without diabetes, much more remains to be known to formulate more effective treatment strategies in this high risk subgroup. PMID- 1512358 TI - Doppler evaluation of aortic valve area in children with aortic stenosis. PMID- 1512359 TI - On measuring "agreement" and not "correlation". PMID- 1512360 TI - Prodromal symptoms of heart attacks. PMID- 1512361 TI - Finn offers testimony on nutrition and the elderly. PMID- 1512362 TI - How the new strategic plan works--for you. PMID- 1512363 TI - Comparison of dietary self-reports with energy expenditure measured using a whole room indirect calorimeter. AB - In this study we used a whole-room indirect calorimeter to evaluate the accuracy of self-reported food intake. Daily measured energy expenditure was compared with 2 weeks of self-reported food intake. Additionally, oxidation of each macronutrient was compared with its self-reported intake to assess the accuracy of self-reported dietary composition. Participants (23 through 60 years old) were eight dietitians, eight subjects who were trained in keeping dietary records, and eight subjects who were not trained. Physical activity in the calorimeter was matched to usual daily physical activity. Overall, measured energy expenditure was approximately 200 kcal/day higher than reported metabolizable energy intake. However, this was the result primarily of a few subjects whose self-reported food intake was considerably below measured energy expenditure. Subjects who were trained in record keeping did not differ from untrained subjects. Dietitians had the lowest difference between intake and expenditure; none of them had the large discrepancies between intake and expenditure seen in the other groups. In all groups, there was a much greater discrepancy between self-reported intake and oxidation of each macronutrient than between self-reported total energy intake and expenditure. PMID- 1512364 TI - Salary discrepancies between male and female foodservice directors in JCAHO accredited hospitals. AB - This study profiles foodservice directors employed in US hospitals accredited by the Joint Commission on Accreditation of Healthcare Organizations (JCAHO) and examines the effect of gender and work-related characteristics on salary. A 37 item questionnaire was sent to 1,002 randomly selected directors of foodservice programs at JCAHO-accredited hospitals in the United States and Puerto Rico. Usable data were received from 663 directors, a response rate of 66%. Foodservice directors answered questions on background information, work-related information, academic and professional certification, and salary range. Findings indicate that foodservice directors are predominantly white, female, college graduates, and more than half are registered dietitians. On the average, foodservice directors had 16 years of experience in foodservice, had spent 9 years with their current employer and 6 years in their present position, and worked a mean of 48 hours each week; more than two thirds earned greater than $30,000. Salaries, however, were significantly higher for men than for women. When controlling for experience (employment in foodservice, years with present employer and in present position), size of hospital, academic preparation, and professional certification, salaries remained consistently higher for men. Although the dietetics profession is predominantly female, gender appears to be the major factor accounting for inequalities in salaries. These findings may alert hospital administrators of the need to review hiring practices and establish standards that promote equitable salary opportunities for persons most qualified for positions, regardless of gender. PMID- 1512365 TI - Dietary and anthropometric assessment of adults with cerebral palsy. AB - Research on nutrition and cerebral palsy (CP) has been directed at newborns and young children, leaving practitioners with a limited understanding of the nutritional status of the adult population. The purpose of this study was to determine the anthropometric profile and nutrient intakes of 86 adults with cerebral palsy. When compared with growth standards for healthy individuals, the mean body fat percentages and body mass indexes of both men and women with CP were within the normal range. However, 40% of the sample had heights below the 5th percentile for their age and gender, indicating permanent growth stunting. In general, the diets of these individuals were similar to the typical American diet. Both men and women had low nutrient adequacy ratios (NARs) for calcium (0.86 and 0.76, respectively); the women also had low NARs for iron (0.69) and niacin (0.86). Although nutrients obtained from supplements were not included in the NAR score, 26% of the men and 50% of the women reported using nutritional supplements. Fifty-five percent of the sample reported feeding problems. Multivariate analysis illustrated that individuals who participated in regular exercise programs had significantly higher mean adequacy ratios and lower body fat percentages than those who did not exercise regularly. PMID- 1512366 TI - Reducing fat and sodium in school lunch programs: the LUNCHPOWER! Intervention Study. AB - This study developed, implemented, and evaluated a healthful school lunch program that provided tasty food choices that were lower in fat and sodium. The LUNCHPOWER! Intervention Program was implemented in 34 elementary schools in four school districts that represented diverse geographic areas of Minnesota. A team of registered dietitians, foodservice directors, and cook managers reduced the fat and sodium content of school lunches by modifying recipes and food preparation methods and by identifying and selecting vendor products (prepared food products) that were lower in fat and sodium. Nutrition education messages for students and parents were developed for the 5-month intervention. Monthly menus were analyzed for fat, sodium, and energy content before and after the intervention. There was a significant decrease in both total grams of fat and percent of energy from fat between baseline and follow-up. At all 34 schools, mean daily amount of total fat in the lunch menu decreased 39% (from 32 g to 20 g) and percent of energy from fat decreased 29% (from 40% to 28%). We found that schools could serve lower-sodium and lower-fat meals and retain student participation in the school lunch program. PMID- 1512367 TI - Short, thin, or obese? Comparing growth indexes of children from high- and low poverty areas. AB - This study compared the growth indexes of first-grade, white children living in geographic areas of high poverty (n = 281) and low poverty (n = 442) in the state of Washington. Obesity was the most common growth deviance observed in these children. In the low-poverty area, 18% of children had a weight for height greater than the 90th percentile on the National Center for Health Statistics (NCHS) growth standards, whereas only 12% of children from the high-poverty area were in this category. Neither area had high numbers of children with reduced weight for height (less than the 10th percentile on the NCHS growth standards), but children from the high-poverty area were almost twice as likely to be short for their age; 9% of children from the high-poverty area and 5% of children from the low-poverty area had height-for-age values less than the 10th percentile on the NCHS growth standards. Criteria used to determine students' eligibility for financial support for school lunch did not accurately identify children who were thin or short. The prevalence of obesity in these first-grade children suggests that school-based growth screening as well as weight management and physical fitness programs are needed to identify and avert childhood obesity. PMID- 1512368 TI - Trends in prevalence and magnitude of vitamin and mineral supplement usage and correlation with health status. AB - The 1980 Food and Drug Administration Vitamin and Mineral Supplement Use Survey and the 1986 National Health Interview Survey used similar questions and procedures to estimate and identify trends in the prevalence and magnitude of supplement usage in the United States. A comparison of the two surveys reveals that prevalence of supplement use among adults decreased slightly, from 42% in 1980 to 38% in 1986. The magnitude of supplement use has also decreased; users reported taking a mean of 2.15 supplements in 1980 compared with a mean of 1.77 in 1986. The prevalence of supplement users identified as light users increased from 42% in 1980 to 57% in 1986. Supplement usage was more likely and more intense among individuals who had one or more health problems and among individuals who perceived their health as very good or excellent. The findings indicate that supplement usage remains a widespread behavior linked to popular conceptions of good health and well-being but one that is susceptible to change. PMID- 1512369 TI - Effect of nutrition on the health of the elderly. AB - Nutrition may play a role in the progressive decline of several body functions with aging. Progressive decline in energy, lean body mass, and protein intake are also associated with aging. Many elderly (greater than 55 years old) drink less than the recommended amounts of water and consume less than the Recommended Dietary Allowances of calcium, iron, zinc, copper, thiamin, riboflavin, folate, and vitamins B-12 and D. Nutrition needs of the elderly to maintain activities of daily living are expected to increase in future years. Because diminished physical activity and old age disabilities cause the elderly to modify eating habits acquired at a younger age, dietary and other life-style changes should be implemented early in life so that optimal tissue function will be maintained. More research and development is needed in the areas of nutrient requirements for the elderly, effect of nutrition on chronic diseases, improved methods for assessing nutritional status and screening the elderly for nutritional risk, nutrient-nutrient and nutrient-drug interactions, and educational strategies to provide better nutrition and eliminate health fraud. Dietary interventions show promise, but must be monitored for effectiveness. PMID- 1512370 TI - Malnutrition in the institutionalized older adult. AB - Most older adults in the United States live at home and are well nourished. Approximately 5% to 6% reside in nursing homes, and this segment of the older population typically suffers from multiple diseases that contribute to a high incidence of malnutrition. Forty percent of hospital beds are occupied by older persons. This article addresses the causes of malnutrition in older persons institutionalized in long-term and acute-care facilities. The causes include changes in nutrient requirements secondary to disease processes and drug modalities in combination with low or marginal dietary intake. Infections are common and result in anorexia, poor dietary intake, and malnutrition, which predispose the patient to another infection. Occurrence of decubitus ulcers is related to nutritional status and presents a serious risk for older persons with limited mobility. Depression and dementia are commonly seen in older persons and are major contributors to poor appetite and malnutrition. Cancer cachexia accounts for about half of the cases of malnutrition in older institutionalized persons. Physiologic changes that occur with age and multiple drug use place older persons at a high risk for adverse drug reactions. Less body water in the older individual influences and complicates many aspects of treatment. Standards, methods, and interpretation of nutritional assessment measurements in older persons differ from those in younger adults. The nutrition care provider must carefully consider many complex physical, medical, and psychosocial factors to deliver individualized nutrition care. PMID- 1512371 TI - Characteristics of successful dieters as measured by guided interview responses and Restraint Scale scores. PMID- 1512372 TI - Development of a program in accord with JCAHO standards for counseling on potential drug-food interactions. PMID- 1512373 TI - Weekend home-delivered meals in Elderly Nutrition Programs. PMID- 1512374 TI - Food and nutrient intake of white, pregnant adolescents. PMID- 1512375 TI - Relation of dietary barriers in patients with insulin-dependent diabetes mellitus to different modes of treatment. PMID- 1512376 TI - Practice guidelines for nutrition care by dietetics practitioners for outpatients with non-insulin-dependent diabetes mellitus: consensus statement. AB - In summary, nutrition practice guidelines for dietitians who provide outpatient care for persons with NIDDM provide a roadmap for nutrition care that allows for consistency in individualized care. A field test that compares care according to practice guidelines with usual or basic care can provide evidence, based on medical, education/behavior, and cost outcomes, that practice guidelines are not only reasonable and realistic but also effective. PMID- 1512377 TI - Practice guidelines for nutrition care by dietetics practitioners for outpatients with non-insulin-dependent diabetes mellitus: methodologies for field-testing and cost-effectiveness analysis. PMID- 1512378 TI - The American Dietetic Association, 75th annual meeting. Washington, D.C., October 19-22, 1992. Abstracts. PMID- 1512379 TI - Decline in physical function following hip fracture. AB - OBJECTIVE: The main objective of the study was to determine the change in physical function following hip fractures in a community-living elderly population. A secondary objective was the determination of baseline factors predictive of altered function following hip fracture. DESIGN: Prospective, cohort study. SETTING: Urban, community-living elders. PARTICIPANTS: 120 members of a cohort of 2806 individuals age 65 and older in New Haven, CT who sustained a hip fracture from 1982 to 1988 and were treated in the two New Haven hospitals. OUTCOME MEASURE: Self-reported performance of dressing, transferring, walking across a room, climbing stairs, and walking one-half mile before the fracture occurred and 6 weeks and 6 months post-fracture. Baseline factors were assessed before the hip fracture occurred. RESULTS: Of the 120 cohort members who sustained a hip fracture in the 6-year study period, 22 died within 6 months of the fracture. Among survivors there was a sustained decline in function at 6 weeks after the fracture with little improvement by 6 months. At baseline, 86% could dress independently versus 49% at 6 months; 90% could transfer independently versus 32% at 6 months; 75% could walk across a room independently versus 15% at 6 months; 63% could climb a flight of stairs versus 8% at 6 months; and 41% could walk one-half mile versus 6% at 6 months. Physical function and mental status were the only baseline factors significantly associated with physical function at 6 months after the fracture in bivariate analysis, while physical function and depression were associated in multivariate analysis. CONCLUSION: We found a substantial decline in physical function following hip fracture in a prospectively followed community-living elderly population. Only pre-morbid physical and mental function predicted this decline. PMID- 1512380 TI - Surgical results and complications in elderly patients with benign lesions of the spinal canal. AB - OBJECTIVE: To describe the long-term outcome and complications of spinal surgery in a population of elderly patients. DESIGN: Retrospective chart review and clinical follow-up. SETTING: A 700-bed tertiary care midwestern hospital. PATIENTS: Patients 70 years of age or older who underwent elective surgical procedures for the treatment of benign lesions of the spinal canal. MAIN OUTCOME MEASURES: Data obtained from chart review included age, sex, nature and duration of neurological symptoms, activities of daily living (ADL), associated illnesses, length of hospitalization, type of surgery, and complications attributable to surgery. Outcome measurements included changes in neurological symptoms and ADL and a standardized scale obtained from consecutive outpatient visits, telephone interviews, or written responses. RESULTS: Seventy-eight patients with lumbar canal stenosis or soft disc herniations underwent laminectomies, foraminotomies or discectomies. Eleven patients underwent cervical laminectomies for multilevel spondylitic myelopathy. Limb and spine pain were the most common neurological symptoms in patients with lumbar lesions; diminished ADLs were present in eight patients with cervical myelopathies. Six patients died of unrelated causes, and 78 were followed for an average of 27.1 months. Twenty-three (85.2%) of 27 patients with lumbar disc herniations reported improvements or resolution of limb pain while 35 (81.4%) of 43 patients with lumbar canal stenosis reported fair or good results. Five of eight patients with multilevel cervical spondylosis reported improvements of myelopathic symptoms. Twenty-six (28.6%) complications were attributable to 91 surgical procedures including five severe complications and one fatality. Patients with three or more associated illnesses demonstrated a significantly higher incidence of postoperative complications. CONCLUSIONS: Elderly patients with benign lesions of the spinal canal may achieve significant reduction in limb pain and increases in ADL following appropriate surgery, with a tolerable rate of severe complications. The preoperative physical condition of the elderly patient served as an indicator for operative morbidity. PMID- 1512381 TI - Joint impairment and hand function in the elderly. AB - OBJECTIVE: To test the contribution of joint impairment to observed hand function (grip strength and Williams Test) in the elderly, using a multivariate model. DESIGN: Cross-sectional observational data (baseline data from an ongoing longitudinal study). SUBJECTS: Five hundred forty-one persons over age 60, including continuing care retirement community (n = 222), homebound (n = 72), and ambulatory (n = 247) respondents. Mean age at assessment 76.7, (SD = 9.0). MEASUREMENT: Independent variables included sociodemographics, physician measures of upper joint impairment, an index of comorbidities derived from physical examination or chart abstract, self-assessed arthritis pain, depression, and anxiety. The dependent variables included grip strength and a modified Williams Test [Williams Test (M)]. MAIN RESULTS: The multiple regression explained 59% (Adjusted R2 = .59) of the variance in grip strength, with joint impairment accounting for a change in R2 of .07. Upper joint impairment and grip strength accounted for 3% and 5%, respectively, of the variance in the Williams Test (M) (total amount of explained variance = 45%). CONCLUSIONS: Demographics explain most of the variance in grip strength and performance on the Williams Test (M). Controlling for demographics, musculoskeletal disease represented by joint impairment is associated with diminished grip strength. Reduced grip strength is associated with poorer performance on the Williams Test (M). PMID- 1512382 TI - Geriatricians' attitudes toward assisting suicide of dementia patients. AB - OBJECTIVE: To identify geriatricians' attitudes toward assisting suicide of dementia patients, with particular reference to the case of Janet Adkins/Dr. Kevorkian. DESIGN: Mailed questionnaire survey. SETTING: Four distinct geographical regions of the US: Far West, Midwest, Southeast, and Northeast. PARTICIPANTS: All 1,381 ABIM-certified internist geriatricians in the four regions; 727 (52.6%) responded. MAIN OUTCOME MEASURES: Positive, negative, or unsure responses to questionnaire items; comparison of responses between geographical regions. RESULTS: Sixty-six percent of respondents felt that Dr. Kevorkian's assistance of Janet Adkins' suicide was not justifiable, while 14% stated it was morally justifiable. Twenty-nine percent felt Janet Adkins' decision to commit suicide was morally wrong, while 49% stated it was not morally wrong. If the responding geriatricians themselves were diagnosed as having a dementing illness, 41% would consider suicide a possible option; 39% would not consider suicide. Twenty-six percent favored easing restrictions on physician assisted suicide of competent dementia patients, while 57% opposed this. If current restrictions were eased, 21% would consider assisting suicide of competent dementia patients, and 66% would not. Respondents' attitudes showed some significant (P less than or equal to 0.05) variations by geographical region. Where regional differences were observed, respondents in the Midwest tended to show more conservative attitudes toward physician-assisted suicide than those in the Far West and Northeast. CONCLUSIONS: Most responding geriatricians would not consider assisting suicide of dementia patients, and most oppose easing restrictions on physician-assisted suicide. Many, however, could accept the (unassisted) suicide of a competent dementia patient, and many would consider suicide themselves if stricken with dementia. PMID- 1512383 TI - Comorbid mental and substance disorders among older psychiatric patients. AB - OBJECTIVE: To investigate the rate and configurations of current comorbid mental and substance disorders among older psychiatric patients. DESIGN: A descriptive, retrospective study. SETTING: A non-acute, public residential psychiatric treatment facility for adults 55 years of age and older (mean length of stay: 3 months). PATIENTS: 128 patients discharged during a 2-year period. MEASURES: DSM III-R diagnoses, demographic and history data. RESULTS: The overall prevalence rate of concurrent mental and substance disorders during the present treatment episode was 21%. This is comparable to the 6-month rate of 19.8% found in the Epidemiological Catchment Area Study among adults in treatment (all ages). Nearly 50% of the dually diagnosed subsample received more than two diagnoses, with 60% of the subsample receiving a personality disorder diagnosis. Concurrent affective, alcohol, and personality disorder diagnoses were common. CONCLUSION: Older patients with comorbid substance-use and mental disorders may differ substantively from comorbid younger patients. Among older patients in an intermediate-term psychiatric facility, the triple occurrence of alcoholism personality disorder and depression was common. PMID- 1512384 TI - Behavioral disturbance in severe Alzheimer's disease: a comparison of family member and nursing staff reporting. AB - OBJECTIVE: The purpose of this study is to describe the behavioral disturbances in a group of patients with severe Alzheimer's disease and to compare family members' and nursing staff members' perceptions regarding these behaviors. DESIGN: Cross-sectional survey. SUBJECTS: The 33 subjects resided in nine different long-term care facilities in the Rochester, NY area and were selected from a group of patients enrolled in a longitudinal research study of Alzheimer's disease, based on having severe disease. OUTCOME MEASURES: Caregivers were surveyed with a self-administered questionnaire. The primary outcome measures were the prevalences of 13 behaviors and the magnitude of caregiver concern reported by each group of caregivers. RESULTS: Compared with family members, nurses reported more concern with vegetative behaviors (incontinence, dietary change, and sleep disturbance; P = 0.055). There was statistical evidence that the number of behaviors reported by the nurses decreased with increasing disease severity (P = 0.002). Although not statistically significant, the magnitude of concern reported by the nurses also decreased with increasing disease severity (P = 0.063). Family members and nurses frequently disagreed about the presence of many behaviors exhibited by individual patients, and the responses of caregivers within the same group were highly variable. CONCLUSION: Institutionalized patients with severe Alzheimer's disease continue to exhibit troublesome behaviors although overall behavioral disturbance and concern appear to decrease with increasing disease severity. The assessment of these behaviors and their impact on caregivers can be very subjective, depending in part on the role of the caregiver. PMID- 1512385 TI - A comparison of caregivers for elderly stroke and dementia victims. AB - OBJECTIVE: To compare elderly co-resident caregivers of stroke and dementia patients on measures of burden and psychological morbidity. DESIGN: Cohort study. SETTING: Caregivers interviewed at home. SUBJECTS: Convenience sample, 99 co resident caregivers of dementia and stroke patients registered with a community rehabilitation and geriatric service and who were 60 years or over. MAIN OUTCOME MEASURES: Caregiver burden as measured by self-administered questionnaire and subsequent interview, using the Relatives Stress Scale (RSS) and psychological morbidity as measured on the General Health Questionnaire (GHQ). RESULTS: Forty six percent of caregivers had significant psychological morbidity (GHQ greater than 4). Mean RSS score was 12.2 (SD 5.4). No significant differences were found between stroke and dementia caregivers on these measures. Caregiver burden was significantly correlated with psychological morbidity in both caregiver groups. Behavior and mood disturbance in the patient was significantly correlated with burden (dementia caregivers r = 0.66; stroke caregivers r = 0.49, P less than 0.0001) and psychological morbidity (dementia caregivers r = 0.44, P less than 0.01; stroke caregivers r = 0.30, P less than 0.05). Caregiver's dissatisfaction with participation in life activities was correlated with burden (dementia caregivers r = 0.58; stroke caregivers r = 0.63, P less than 0.0001) and psychological morbidity (dementia caregivers r = 0.67, stroke caregivers r = 0.56, P, 0.0001). CONCLUSION: Elderly co-resident caregivers for stroke and dementia patients experience similar degrees of burden and high levels of psychological morbidity. Psychiatric aspects of chronic disability, rather than physical aspects, were found to be more stressful to caregivers. All assessments of the disabled elderly should include measures of caregiver burden and psychological distress. PMID- 1512386 TI - Fluoxetine in elderly patients: is there cause for concern? AB - OBJECTIVE: To assess whether fluoxetine use is associated with significant weight loss or other side effects in depressed elderly patients with concomitant medical illness. DESIGN: A retrospective chart review. SETTING: A tertiary care VA hospital. PATIENTS: Five groups of outpatients were studied: (1) patients greater than 75 years old receiving fluoxetine (n = 15); (2) patients 60 to 71 years old receiving fluoxetine (n = 20); (3) patients greater than 75 years old receiving nortryptiline or desipramine (n = 20); (4) patients greater than 75 years old with a history of depression but on no antidepressant medication (n = 20); and (5) patients greater than 75 years old with no history of depression (n = 28). MEASUREMENTS: Mortality, change in weight, reports of anorexia or nausea, and serum sodium and glucose measurements. MAIN RESULTS: Patients greater than 75 years of age taking fluoxetine experienced significantly greater weight loss (average 4.6 kilograms, P = 0.0062) than the other groups. Both groups of patients taking fluoxetine were significantly more likely to report nausea (P = 0.0095) and anorexia (P = 0.0009). No significant differences were noted in mortality or the frequency of hypoglycemia or hyponatremia between groups. CONCLUSION: The frequency and degree of weight loss noted here in medically ill elderly receiving fluoxetine warrants further investigation. PMID- 1512388 TI - Modeling recovery from stumbles: preliminary data on variable selection and classification efficacy. AB - OBJECTIVE: The primary purpose of this preliminary investigation was to determine the functional relationship between selected information processing time and response execution variables and measures of postural stability in elderly women. A secondary purpose was to explore the efficacy of a neuromotor model using selected variables to retrospectively identify subjects with a self-reported history of falling. DESIGN: Descriptive, retrospective, cohort. SETTING: General community. SUBJECTS: Convenience sample of 17 community-dwelling females with a mean age of 72.2 years. MAIN OUTCOME MEASURES: Postural stability variables included the amplitude and frequency of postural sway during static vision-aided no-vision conditions. Information processing and response execution variables were collected using a simple-choice reaction time paradigm for an isometric knee extension task. RESULTS: Postural stability and information processing variables were functionally independent. Based upon significant intergroup differences, simple and choice pre-motor reaction time and non-vision aided anterior posterior sway amplitude were selected for inclusion in a discriminant analysis. The resulting discriminant function was significant (P = 0.01), correctly categorizing all of the subjects with a self-reported history of falling and identifying six out of seven of the non-fallers. CONCLUSIONS: These preliminary results suggest that it is feasible to identify a predisposition to falling by detecting an inability to respond successfully to a postural disturbance. PMID- 1512387 TI - Factors attenuating the validity of the Geriatric Depression Scale in a dementia population. AB - OBJECTIVE: The validity of the Geriatric Depression Scale (GDS) in cognitively impaired patients has been questioned. We investigated possible factors (memory loss, dementia severity, unawareness of illness) attenuating the validity of the GDS in patients with dementia. PATIENTS: Eighty-three patients who met research diagnostic criteria for "probable Alzheimer's disease." Subjects with major depressive disorder were excluded. Dementia severity ranged from mild to moderate. SETTING: Outpatient clinics, including institutional settings and private research settings. MEASUREMENTS: Depression--GDS; Hamilton Depression Scale. Memory--Wechsler Memory Scale; Benton Visual Retention Test. Dementia severity--Mini-Mental State Examination. Self-awareness of cognitive deficits- Difference score between a self-report memory questionnaire and an informant rated memory questionnaire. RESULTS: Multiple regression analysis revealed that Hamilton scores were the major predictor of GDS scores. Memory scores and self awareness scores were also significant predictors. Dementia severity scores were not a significant predictor. CONCLUSIONS: The GDS is a valid measure of mild-to moderate depressive symptoms in Alzheimer patients with mild-to-moderate dementia. However, Alzheimer patients who disavow cognitive deficits also tend to disavow depressive symptoms, and the GDS should be used with caution in such patients. Finally, the argument that memory impairment precludes accurate self report of recent mood is negated by our finding that many patients accurately reported depressive symptoms and that worse memory was associated with more self reported depressive symptoms. PMID- 1512389 TI - Valproate treatment of older psychotic patients with organic mental syndromes and behavioral dyscontrol. PMID- 1512390 TI - Clinical decisions in the care of elderly persons with AIDS. PMID- 1512391 TI - The mini-mental state examination: a comprehensive review. AB - OBJECTIVE: The purpose of this paper is to provide a comprehensive review of information accumulated over the past 26 years regarding the psychometric properties and utility of the Mini-Mental State Examination (MMSE). PARTICIPANTS: The reviewed studies assessed a wide variety of subjects, ranging from cognitively intact community residents to those with severe cognitive impairment associated with various types of dementing illnesses. MAIN OUTCOME MEASURES: The validity of the MMSE was compared against a variety of gold standards, including DSM-III-R and NINCDS-ADRDA criteria, clinical diagnoses, Activities of Daily Living measures, and other tests that putatively identify and measure cognitive impairment. RESULTS: Reliability and construct validity were judged to be satisfactory. Measures of criterion validity showed high levels of sensitivity for moderate-to-severe cognitive impairment and lower levels for mild degrees of impairment. Content analyses revealed the MMSE was highly verbal, and not all items were equally sensitive to cognitive impairment. Items measuring language were judged to be relatively easy and lacked utility for identifying mild language deficits. Overall, MMSE scores were affected by age, education, and cultural background, but not gender. CONCLUSIONS: In general, the MMSE fulfilled its original goal of providing a brief screening test that quantitatively assesses the severity of cognitive impairment and documents cognitive changes occurring over time. The MMSE should not, by itself, be used as a diagnostic tool to identify dementia. Suggestions for the clinical use of the MMSE are made. PMID- 1512392 TI - Psychotherapeutic medications in the nursing home. Board of Directors of the American Association for Geriatric Psychiatry, Clinical Practice Committee of the American Geriatrics Society, and Committee on Long-Term Care and Treatment for the Elderly, American Psychiatric Association. PMID- 1512393 TI - Research with Alzheimer's disease subjects: informed consent and proxy decision making. AB - Because patients with Alzheimer's disease are on a path of declining capacity to give consent, advancement of research with Alzheimer's disease subjects presents challenging and perplexing ethical and legal dilemmas. Although generic regulations for the protection of human subjects apply, special considerations for cognitively impaired dementia subjects have depended on local Institutional Review Boards and relevant state laws and regulations, producing a lack of uniformity regarding encouragement of research and protection of subjects. Discussed are the dilemmas encountered in advancing research with Alzheimer's disease subjects, including (1) issues about informed consent, (2) determination of decision-making capacity (competency), (3) problems in dealing with subjects of mild and fluctuating impairment, and (4) proxy and advance consent measures for severely impaired subjects. Proposed is an agenda of ethical research needs for advancing biomedical research on Alzheimer's disease. Needed are empirical studies concerning recruitment of Alzheimer's disease subjects, the actual processes of informed consent, and the difficulties encountered by researchers, collaborative development of tests for both diagnosing Alzheimer's disease and assessing subjects' capacities to provide informed consent, and exploration of innovative uses of advance and proxy consents for participation in Alzheimer's disease research. PMID- 1512394 TI - The impact of OBRA on medical practice within nursing facilities. AB - Major changes in the federal oversight of nursing home care were passed by Congress and became law as the Nursing Home Reform Amendments of the Omnibus Budget Reconciliation Act of 1987 (OBRA 87). The final regulations to implement OBRA 87 were published in September, 1991. The intent of this article is to provide an overview of selected parts of the nursing home reform regulations, which have a direct impact on physician practice within nursing facilities, and to offer strategies for successful management of the changes that are required. A brief review of the origins of the legislation and the process by which law is turned into practice is provided as a context in which to understand the changes mandated by the Nursing Home Reform Amendments of OBRA 87. PMID- 1512395 TI - Geriatric education. Part I: Efficacy of a mandatory clinical rotation for fourth year medical students. AB - OBJECTIVES: To describe the curriculum of a mandatory, fourth-year geriatrics clerkship and assess its impact on medical students' knowledge of geriatric medicine and attitudes toward the elderly. DESIGN: One group, before/after trial. SETTING: Mount Sinai School of Medicine of the City University of New York. PARTICIPANTS: Entire fourth year class of medical students (n = 127). INTERVENTION: Four-week-long clinical geriatrics clerkship. MEASUREMENTS: Pre- and post-rotation: test of knowledge; Aging Semantic Differential (ASD) attitude scale; Modified Maxwell-Sullivan attitude scale; questionnaire. MAIN RESULTS: Seventy percent of students found the rotation to be educationally valuable; however, only one-third of students would have taken the clerkship had it not been required. Mean geriatric knowledge score increased by 18.7% (P less than 0.001). Mean ASD attitude score did not change significantly (130.5 +/- 19.2 pre rotation versus 126.6 +/- 18.8 post-rotation, P = 0.15), but students started the rotation with a neutral attitude. Over 90% of students agreed they would welcome elderly into their future practice. CONCLUSION: If a national curricular goal is to improve medical students' knowledge of geriatric medicine, required rather than elective rotations may be in order. PMID- 1512396 TI - Geriatric education. Part II: The effect of a well elderly program on medical student attitudes toward geriatric patients. AB - OBJECTIVE: To assess impact of exposure to healthy elderly on medical students' attitudes toward the elderly. DESIGN: Prospective, randomized, controlled intervention trial. SETTING: Community-based Well Elderly Program. PARTICIPANTS: Ninety-three fourth year medical students on a required Geriatric Medicine clerkship who were assigned to either a tertiary care university medical center or a teaching nursing home. INTERVENTION: Thirty-five students were randomly assigned to participate in a Well Elderly Program and were compared to a control group of 58 students at equivalent sites who did not participate. MEASUREMENTS: Pre- and post-rotation, students were given the Aging Semantic Differential (ASD), a validated geriatric attitudinal scale. MAIN RESULTS: By repeated measures analysis of variance, the difference between pre- and post-rotation ASD scores were most significant for students who participated in the Well Elderly Program; site did not exert a significant interaction effect. CONCLUSION: These results underscore the importance of exposure to healthy older people on effecting positive attitude changes among medical students on geriatrics rotations. PMID- 1512397 TI - Total quality assurance: an important step in improving care for older individuals. PMID- 1512398 TI - A short questionnaire estimating risk of malnutrition. PMID- 1512399 TI - Psychosocial factors in geriatric care. PMID- 1512400 TI - Optometry: the invisible member of the rehabilitation team. PMID- 1512401 TI - The effect of head trauma on the visual system: the doctor of optometry as a member of the rehabilitation team. AB - Brain injury results from either head trauma or strokes and causes many visual and visually related disturbances. Rehabilitation is aimed at developing skills that allow the patient to optimally function as a viable and independent member of society. Often the resultant visual deficits remain undiagnosed and untreated, which hinder the patient's total rehabilitation. Optometric evaluation of brain injured patients should routinely be performed as part of the transdisciplinary team approach to rehabilitation. Optometrists are uniquely qualified to diagnose and treat visual and functional deficits of the visual system in the brain injured population. The purpose of this paper is to present a rationale for optometric participation in the rehabilitation of head trauma and stroke patients. PMID- 1512402 TI - An overview of head trauma for the primary care practitioner, Part I--Etiology, diagnosis, and consequences of head trauma. AB - At some point in their careers, most primary care providers will encounter patients who have sustained some degree of traumatic head or brain injury. This article presents an overview of the causative mechanisms responsible for this trauma, the nature of the injuries sustained, some relevant initial medical diagnostic procedures performed, and possible consequences encountered. An emphasis has been placed on familiarizing the primary care provider with specific terminology associated with head trauma incidents. PMID- 1512403 TI - An overview of head trauma for the primary care practitioner: Part II-Ocular damage associated with head trauma. AB - The forces that produce head and brain trauma can also produce primary and secondary damage to the eye and vision. A brief overview of potential damage is presented for each structure of the eye to give the primary care practitioner or initial examining physician a familiarity with conditions that must be considered in the evaluation of the head trauma patient. Certain primary care therapies are also noted. PMID- 1512404 TI - The primary care optometric evaluation of the traumatic brain injury patient. AB - Traumatic brain injury can cause an assortment of visual problems for the patient. These problems, unless resolved, can hinder a patient's rehabilitative progress. This article discusses the characteristic visual deficits found after traumatic brain injury. It also explains how minor modifications made to a routine comprehensive optometric examination can tailor an examination to the head trauma patient. PMID- 1512405 TI - The differential diagnosis of perceptual deficits in traumatic brain injury patients. AB - This article describes a perceptual testing battery useful in the evaluation of the traumatic-brain-injury patient. Areas of visual perceptual deficits significant in this population are discussed. Key tests, familiar to optometrists, are indicated for the evaluation of these areas. A differential diagnosis based on the results of these tests can be made. This allows for an effective visual rehabilitation program to be developed for these patients. PMID- 1512406 TI - Head trauma and low vision: clinical modifications for diagnosis and prescription. AB - Head-trauma patients benefit from many optical and non-optical devices usually associated with low vision care. This article reviews the most common modifications of clinical examination techniques required to facilitate the evaluation of trauma patients who may benefit from or require low vision devices. A discussion of the importance of incorporating common optical and non-optical devices which can enhance the lives of traumatized patients will follow. PMID- 1512407 TI - Optometric therapy for the left brain injured patient. AB - This article discusses the role of optometric visual therapy in the rehabilitation of left head trauma patients. It overviews the functions of the left hemisphere and the consequences of traumatic brain injury. A patient who was helped by this perceptual therapy is presented. An overview of the therapy approach used for this patient is discussed. PMID- 1512408 TI - Optometric management of binocular dysfunctions secondary to head trauma: case reports. AB - Extropia, esotropia, hyper elements, visual sequencing problems, accommodative dysfunctions and inefficient Motor Planning are common consequences of head trauma. Optometric visual therapy is an effective treatment modality for these dysfunctions. Two case reports are presented in order to illustrate optometric management of patients exhibiting these problems secondary to head trauma. PMID- 1512409 TI - The utilization of a temporal mirror coating on the back surface of the lens as a field enhancement device. AB - A 37-year-old male had a right homonymous hemianopia due to trauma. During his initial low vision assessment, a small clip-on mirror was dispensed to help him compensate for his field loss. At follow-up, he reported satisfaction with the mirror. He also reported that novelty "look behind you" sunglasses were beneficial to him and less conspicuous than the clip-on mirror. He requested temporal mirror coating on otherwise clear lenses so that he could utilize the glasses at night or on cloudy days. We fabricated this for him and also mounted a small mirror nasally within the vertex distance behind his frame. The fabrication of the two devices will be discussed as well as a comparison of these three field enhancement devices. PMID- 1512410 TI - Clinical research and statistical analysis of a visual field awareness system. AB - This article discusses the clinical research and applications of the statistical analysis of a system called "The Visual Field Awareness System." This medical lens system allows patients with a visual field loss to 1) scan toward area of the loss, to see objects sooner and more clearly, and 2) demonstrate increased function and safety. Seventy-nine percent (27 of 34) of the patients in the sample received and accepted the prism treatment. Of this group, a minimum of 70 percent (19 of 27) continue to benefit from this treatment strategy. Statistically significant predictors of success are discussed. This study demonstrates that patients suffering visual field loss may show functional benefit by the utilization of this prism treatment along with vision rehabilitation. PMID- 1512411 TI - Psychosocial aspects of vision loss associated with head trauma. AB - The adjustment to sudden and severe vision loss is always difficult. However, when vision loss is the result of head trauma, additional psychological and psychosocial factors complicate the adjustment process. Patients often must cope with a variety of cognitive and personality changes that dramatically affect the ability to adapt to physical limitations. PMID- 1512412 TI - Community resources and third party billing for patients who have had head trauma/head injuries. AB - In order to render full scope care for head trauma patients, optometrists should be familiar with the community resources available for patients with such injuries. In addition, they should have an understanding of third party billing procedures needed to seek reimbursement for the diagnosis and treatment of patients who have suffered such accidents. This article will review each of these topics. PMID- 1512413 TI - The role of occupational therapy in rehabilitating stroke patients. AB - The role of the occupational therapist is outlined. An overview of occupational therapy evaluation and treatment is discussed. The goal of rehabilitation is aimed at helping the patient achieve the highest level of independence of which he is physically capable. A case report is presented. PMID- 1512414 TI - Mitotic activity and cell deletion in ventral prostate epithelium of intact and castrated oxytocin-treated rats. AB - Previous study has shown that oxytocin (OT) attenuated the postcastration regression of ventral prostate epithelium in rats. To decide if this effect is associated with stimulation of cell division or improvement of cell survival, metaphase index of secretory cells and frequency of apoptotic bodies in the epithelium, combined with stereological parameters, were determined in the present study. OT was injected subcutaneously in a dose of 0.25 IU/100 g/d during 5 postorchiectomal days and the same treatment was applied to intact rats. Only the prostate of castrated animals responded to OT. They had greater total volume of the epithelium, total number and metaphase index of secretory cells, but lower frequency of apoptotic bodies. These findings demonstrate the ability of OT to stimulate mitotic activity and to diminish mortality of secretory cells caused by orchiectomy. PMID- 1512415 TI - Mutations of the human thyrotropin-beta subunit glycosylation site reduce thyrotropin synthesis independent of changes in glycosylation status. AB - In recent studies, site-directed mutagenesis has been used to alter the tripeptide glycosylation recognition sequences of glycoprotein hormone subunits, thereby affecting their structure and function. However, it is not known whether these effects result from changes in glycosylation status, amino acid sequence, or both. We therefore studied the synthesis of wild-type and mutant recombinant human thyrotropins produced by transient transfection of a human cell line. Mutating the TSH-beta subunit glycosylation recognition sequence, Asn-Thr-Thr (codons 23-25), to either Gln-Thr-Thr or Asn-Thr-Tyr abolished subunit glycosylation, as demonstrated by the inability to incorporate 3H-carbohydrates. However, a third mutation (Asn-Thr-Ser) contained an intact glycosylation recognition sequence site, and was shown to retain glycosylation. The mutations that abolished TSH-beta subunit glycosylation resulted in greater than 90% decreases in TSH synthesis. However, the glycosylation recognition sequence mutant that retained beta subunit glycosylation exhibited a 70% decrease in TSH production. These decreases were not attributable to the intracellular accumulation of TSH or its free beta subunit. We also engineered two TSH-beta subunit mutations that did not alter the glycosylation recognition sequence. A glycine to arginine mutation adjacent to the glycosylation recognition sequence, in a region thought to be critical for heterodimer formation, abolished TSH production. In contrast, shortening the TSH-beta subunit carboxyterminus by six amino acids increased TSH synthesis.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1512416 TI - Prevalence and characteristics of post-partum thyroid dysfunction: results of a survey from Toronto, Canada. AB - In order to determine the prevalence of post-partum thyroid dysfunction in our region, 1,376 randomly selected mothers were enrolled immediately post-partum and followed prospectively over a 2 year period in a large single-center survey. Beginning at delivery, sequential clinical and laboratory assessments were conducted at 6-8 week intervals up to 1 year post-partum and a questionnaire was administered at 3 months post-partum. Among the 1,376 mothers who qualified for entry into this study, 495 (36%) completed at least 3 months follow-up and 300 (22%) completed at least 1 year of follow-up. Abnormalities in post-partum thyroid function (PTD) were detected in 82 of the 1,376 enrolled mothers for an overall minimum prevalence rate of 6.0%. Hyperthyroidism confirmed to be associated with a low 24h radioactive iodine thyroid uptake (RAIU), compatible with the post-partum painless thyroiditis syndrome (PPT) was documented in 44 (3.2% minimum prevalence of typical PPT) of which 39 (89%) had a typical biphasic (hyperthyroid to hypothyroid) PTD while 5 (11%) had only a hyperthyroid phase with a suppressed RAIU without a subsequent hypothyroid phase. Another 17 (1.2%) had transient hyperthyroidism likely due to PPT but were not confirmed by an RAIU test and did not evolve to a detectable hypothyroid phase; and, 17 mothers (1.2%) had hypothyroidism between 5-7 months post-partum without preceding hyperthyroidism, resulting in an overall minimum prevalence of 5.7% for all variants of PPT. Graves' hyperthyroidism occurred in 3 (0.2%) and toxic nodular goiter was present in 1 (0.07%).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1512417 TI - Idiopathic reactive hypoglycemia: a role for glucagon? AB - We previously reported that patients with idiopathic reactive hypoglycemia (plasma glucose concentration lower than 2.5 mmol/L 2-4 h after the ingestion of 75 g of glucose) display reduced or absent counterregulatory response of the glucagon secretion and increased insulin sensitivity. In order to examine the effect of glucagon on the increased insulin sensitivity in these patients, 12 subjects with idiopathic reactive hypoglycemia underwent a two-step hyperinsulinemic (1 mU/kg.min) euglycemic glucose clamp and were compared with 12 normal control subjects matched for age, weight and sex. During the first step of the glucose clamp (only insulin + glucose infusion) the patients with Idiopathic Reactive Hypoglycemia required higher glucose infusion rates to maintain euglycemia than normal subjects (9.09 +/- 0.29 mg/kg. min vs 7.61 mg/kg.min). When basal glucagon secretion was replaced (+ somatostatin and glucagon, second step of the clamp) the glucose infusion rates required to maintain euglycemia in patients with Idiopathic Reactive Hypoglycemia significantly decreased (to 7.17 +/- 0.40 mg/kg.min) and resulted similar to normal subjects (7.64 +/- 0.41 mg/kg.min). Thus, in patients affected by Idiopathic Reactive Hypoglycemia, glucagon secretion may play an important role in the pathogenesis of the increased insulin sensitivity and hypoglycemia. PMID- 1512418 TI - Changes in central and peripheral nervous system function during hypoglycemia in man: an electro-physiological quantification. AB - We measured somatosensory evoked potentials (SEP) in normal subjects during acute (group A) and moderately prolonged (group B) hypoglycemia. We considered the following parameters: peripheral conduction velocity (wrist-Erb CV), conduction time (CT) between brachial plexus and the cervical cord (Erb-N13) and central CT from the cervical cord/lower brainstem lemniscal pathway to the cortex (N13-N20). In group A, the electrophysiological parameters did not change significantly throughout the study. In group B, mean N13-N20 CT increased from a basal values of 5.82 +/- 0.11 to 6.22 +/- 0.11 msec at 105 min (p less than 0.02) and 6.33 +/- 0.11 msec at 120 min (p less than 0.05). This study indicates that neither acute nor moderately prolonged hypoglycemia influence the peripheral nerve function in normal subjects and provides evidence that hypoglycemia as low as 2.4 mmol/L, lasting more than 60 min, can significantly increase the conduction time of central somatosensory pathways. PMID- 1512419 TI - Idiopathic anterior hypopituitarism: magnetic resonance imaging and clinical correlation. AB - We describe the anatomical abnormalities in the hypothalamic-pituitary region revealed by magnetic resonance imaging (MRI) in 10 patients, 8 men and 2 women, affected by idiopathic anterior hypopituitarism (IAH). In all cases contiguous sagittal and coronal T-1 weighted images were obtained. In 9 patients the high intensity posterior lobe was missing, in almost all patients the pituitary stalk was thin and/or transected, and in 8 a bright T-1 nodule was detected at the infundibular apex, near the tuber cinereum, in the median eminence. None had diabetes insipidus. MRI proves to be very useful in understanding the etiopathogenesis of IAH. PMID- 1512420 TI - Thyroid ultrasonography related to clinical and laboratory findings in patients with silent thyroiditis. AB - We summarized the clinical course of 10 patients with silent thyroiditis and evaluated the clinical usefulness of ultrasonography, in combination with clinical and laboratory findings, for the differentiation from Graves' disease. Serum T3 and T4 were increased in all cases, and the ratio of T3/T4 (ng/micrograms) was 17.8 +/- 3.6 (SD). But in 3 of 10 patients the ratio was greater that 20. TSH receptor antibody (TRAb) and thyroid stimulating antibody (TSAb) were negative in all cases. The estimated thyroid volume by ultrasonography was 18.4 +/- 5.5 ml, which was slightly increased but significantly lower than those in Graves' disease (p less than 0.05). The internal texture of the thyroid showed a decreased echogenicity with a mean echo level of 70.4 +/- 15.4. There was a weak positive correlation between the echo level at the onset of thyrotoxicosis and the lowest T3 level during the clinical course (p less than 0.05). It is suggested that ultrasonography gives a useful information to the diagnosis and outcome of patients with silent thyroiditis. PMID- 1512421 TI - Comparison of Nb2 lymphoma cell bioassay with immunoassay for human prolactin: the role of estrogen. AB - The Nb2 lymphoma cell bioassay (BA-PRL) is a sensitive measure of serum prolactin under physiologic conditions. Since estrogens prime the lactotroph, prolactin heterogeneity and hence bioassayable prolactin may be influenced. A study was performed to observe the effect on BA-PRL of changing estradiol (E2) concentrations. In 13 normal subjects clomiphene citrate was administered to stimulate ovarian activity and blood samples were obtained before and after stimulation. Estradiol, BA-PRL and immunoassayable prolactin (RIA-PRL) were measured. While there was a substantial increase in E2 post-stimulation (p less than 0.001), there was no significant change in BA-PRL, RIA-PRL or BA/RIA-PRL ratios. Despite the lack of change in the mean BA/RIA-PRL ratio over a wide range of E2 concentrations that include and exceed those normally seen in spontaneous menstrual cycles, it is difficult to drawn conclusions regarding an association between E2 and BA/RIA-PRL ratios as there was no discernible change in the concentration of prolactin (possibly due to the antiestrogenic effect of clomiphene citrate). PMID- 1512422 TI - Iodine contamination in subjects admitted to a general hospital. AB - Urinary iodine excretion was measured in 300 consecutive patients admitted to a general hospital for nonthyroidal disease. Iodine contamination (values greater than 300 micrograms l/g creatinine) was found in 29.3% of cases, mostly due to amiodarone and iodinated contrastographic agents. The source of iodine contamination was not detected in 23% of cases. PMID- 1512423 TI - Thyroid function in systemic sclerosis. PMID- 1512424 TI - Anti-thyroid antibodies and hypothyroidism in systemic sclerosis. PMID- 1512426 TI - Excessive testicular progesterone secretion in aged male Fischer 344 rats: a potential cause of age-related gonadotropin suppression and confounding variable in aging studies. AB - Previous studies have inconsistently reported elevated sex steroid levels in aging male F344 rats, which frequently develop testicular Leydig cell tumors. The aims of this study were to characterize circulating steroid levels and to determine the in vivo source and functional significance of altered steroid secretion in these animals. Progesterone (P) and to a lesser extent estradiol (E2) levels were increased, while gonadotropins and testosterone (T) were decreased, in intact 24-mo-old compared to 12-mo-old rats. P levels were inversely correlated with gonadotropins and T. All old rats demonstrated Leydig cell hyperplasia or tumors. After orchidectomy, P levels were markedly decreased. Gonadotropin levels were similar in orchidectomized 24-mo compared to 3-mo-old rats. We conclude that the testis is the source of excessive P and E2 secretion in vivo in old F344 rats. Increased P (or E2) negative feedback may contribute to the suppression of gonadotropins and reproductive function in aging male F344 rats. Finally, excessive P secretion may be a confounding pathological variable in aging studies using this rat model. PMID- 1512427 TI - Aging changes the effects of cocaine on vigilance task performance of rats. AB - To investigate age-related behavioral changes with the administration of cocaine, young (6-10 mo), middle-aged (12-18 mo), young-old (21-24 mo), and old (25-36 mo) rats that had been trained on a 2-choice, discrete trial vigilance task were tested under different doses of cocaine. The young and middle-aged rats exhibited significantly increased accuracy and decreased choice latencies following 2.5 mg/kg cocaine. A 15.0 mg/kg dose increased variability in these measures and increased food retrieval latencies. The young-old and old rats exhibited no significant changes in accuracy or choice latency to 1.25, 2.5, and 5.0 mg/kg cocaine; however, a dose of 15.0 mg/kg significantly reduced accuracy in both these groups and increased choice latencies in the old animals. Also, doses of 5.0 and 15.0 mg/kg tended to increase food retrieval latencies more in the two older groups than in the two younger groups. These results indicate that, rather than a simple increase or decrease in sensitivity, there is a qualitative change in cocaine's behavioral effects as rats age. These findings may reconcile long standing discrepancies in the literature regarding age-related changes in the behavioral effects of amphetamine, with actions and effects very similar to those of cocaine. PMID- 1512428 TI - Use of medications by persons 65 and over: data from the established populations for epidemiologic studies of the elderly. AB - Data were analyzed from household interviews of four population-based cohorts comprising the Established Populations for Epidemiologic Studies of the Elderly to estimate the prevalence of prescription and nonprescription medication use among community-living elderly and to examine sociodemographic and health factors related to medication use. Prescription drugs were used by 60-68% of men and 68 78% of women. Nonprescription drugs were used by 52-68% of men and 64-76% of women. Use of prescription medications generally increased with age although use of nonprescription drugs was not associated with age. Men and women who smoked or used alcohol in the preceding year frequently took medications. Those who reported more depressive symptoms, impairments in physical functioning, hospitalizations, and had poorer self-perceived health status were most likely to take medications. However, 10-29% of respondents with fair or poor self-perceived health took no prescription medications, and 3-13% took neither prescription nor nonprescription medications. While further research appears warranted into potential overmedication of elders, particularly those with many depressive symptoms, these data suggest that studies of potential underuse among elders with poor health are equally important. PMID- 1512429 TI - Nutrient intakes and dietary patterns of older Americans: a national study. AB - To assess the dietary status of older Americans, a national household survey of food consumption practices of individuals 65 years of age and older was conducted in May-August, 1990. The design and methodology of the survey were modeled after those of the USDA's Continuing Survey of Food Intakes by Individuals (CSFII). Dietary information for 474 individuals (65 to 98 years of age) in 355 households was collected by interview (24-hour dietary recall). Analyzed indicators of dietary quality were energy (calorie) and nutrient intake, food group intake and frequency, and number of meals skipped. Results indicated that substantial percentages of those surveyed had inadequate intakes of energy and nutrients. Over 40% of men had intakes of vitamins A and E, calcium, and zinc below two thirds the RDA. For women, over 40% had intakes of vitamin E, calcium, and zinc that were below two-thirds the RDA. Additionally, over 20% of older men and women skipped lunch. These data indicate that a large proportion of noninstitutionalized elderly Americans consume diets that fail to meet dietary standards. PMID- 1512425 TI - Thyroid hormones and growth hormone secretion. PMID- 1512430 TI - The effects of visual factors and head orientation on postural steadiness in women 55 to 70 years of age. AB - This study was designed to establish reference data for the effects of head position and visual conditions on the standing posture of healthy women ages 55 to 70. Center of pressure (CoP) data were analyzed using ANOVA models. Total CoP displacement was 45% greater (significant, p less than .05) when the subjects stood with their heads back and their eyes closed, as compared to standing looking straight ahead. Visual surrounds consisting of vertical visual cues resulted in less postural sway (PS) than surrounds made of horizontal visual cues (significant, p less than .05 for anteroposterior CoP range). Experimentally reduced visual acuity resulted in greater PS, while changes in ambient lighting and spatial frequency of visual cues affected PS minimally. These results suggest that a reduction in the height of shelving, and the provision of high-contrast visual cues and vertical geometric patterns are potential intervention strategies to optimize vestibular sensory input and visual orientational cues for the maintenance of stability during stance. PMID- 1512431 TI - Age-related changes in postural responses preceding rapid self-paced and reaction time arm movements. AB - The electromyographic responses in postural (thigh and trunk) and primary agonist (shoulder) muscles were examined in standing young and older adults prior to rapid self-paced (SP) and simple reaction time (RT) arm flexion movements. In contrast to younger subjects, older adults demonstrated significantly lower frequencies of trials for self-paced movements in which thigh muscle responses preceded the activation of the shoulder muscle. Furthermore, younger adults showed more frequent early lower limb postural responses for SP versus RT movements, whereas older subjects retained comparable frequencies between task conditions. Overall, a significantly shorter intermuscular timing interval between leg and arm muscle onsets was also found for the older group. PMID- 1512433 TI - Altered epithelial lining fluid parameters in old normal individuals. AB - Pneumonia is a leading cause of morbidity and death in older patients, and immunosenescence is believed to contribute to their susceptibility. In order to investigate whether age-related changes occur on the epithelial surfaces of the lung, bronchoscopy and bronchoalveolar lavage (BAL) were performed without complication in 19 young (27.7 +/- 4.2 yrs), 6 middle-aged (49.8 +/- 3.5 yrs), and 8 old (74.1 +/- 4.3 yrs) normal, nonsmoking subjects. BAL was performed by instilling and retrieving five 20 ml aliquots of normal saline into three sites. The returns from the first aliquots (the bronchial sample) were analyzed separately from the returns from the subsequent aliquots (the distal sample). Lavage fluid cellularity was characterized and IgA, IgG, and albumin were measured by ELISA. Lavage fluid returns were lower in the elderly group and correlated with spirometric parameters. Significantly elevated numbers of neutrophils were recovered by the bronchial sample fluid from the old group. In contrast, no consistent difference in macrophage recovery by either the bronchial or distal sample was noted. In both the bronchial and distal samples, IgG, but not IgA or albumin, was elevated in the group of old subjects. Alterations occurring in BAL fluid with aging may reflect changes in local host defenses. PMID- 1512432 TI - Bradykinin-induced venodilation is not impaired with aging in humans. AB - The aim of this study was to determine whether there is an age-related decline in vascular responsiveness to bradykinin, whose vasodilatory action is mediated chiefly through endothelium-derived relaxing factor (EDRF). Dose-response curves for bradykinin were constructed using the dorsal hand vein compliance technique in veins preconstricted with phenylephrine in 27 volunteers (16 male, 11 female) aged 18 to 81 years. At the end of the bradykinin study, 12 subjects had a single infusion of a high dose of isoproterenol. There was no correlation between age and the EMAX or the log ED50 for bradykinin, although the same subjects showed a correlation between age and EMAX for isoproterenol, as previously found. There was no significant difference in either the EMAX or the log ED50 between male and female subjects. The results suggest that bradykinin-induced vasodilation is independent of age or gender. PMID- 1512434 TI - Improving memory and control beliefs through cognitive restructuring and self generated strategies. AB - Memory problems are a major source of concern among older adults. The goal of this research was to evaluate methods for improving memory performance and beliefs about memory ability and control. Men and women between the ages of 60 and 85 were randomly assigned to one of five treatment groups: (1) cognitive restructuring to promote adaptive beliefs about memory, (2) memory skills training, (3) combined cognitive restructuring and memory skills training, (4) practice on memory tasks, and (5) a no-contact control group. Beliefs about memory (ability and control) and memory performance (working memory, recall of text materials, categorizable word list, and names and faces) were assessed at a pretest and two posttests. As predicted, those receiving the combined treatment showed the greatest increases in their sense of control and perceived ability to improve memory. Results indicated that all groups improved equally on the memory tasks, although those who had received memory training were more likely to report at the second posttest that they had begun using new strategies for remembering things. PMID- 1512435 TI - Providing support to others and well-being in later life. AB - Although there is now a voluminous literature on supportive social relations in later life, most of this research has been concerned with assessing the beneficial effects of receiving support from others. The purpose of this study is to assess whether giving support to others within informal as well as formal settings might also benefit older help-providers. Findings from a recent nationwide survey of the elderly suggest that giving informal assistance to others (but not formal assistance) appears to bolster feelings of personal control in later life. The data further reveal that greater feelings of personal control are in turn related to lower levels of depressive symptomatology. PMID- 1512436 TI - Long-term effects of a structured life review process. AB - This study examined the long-term effects of a structured life review process in a group of 52 homebound elderly clients. Subjects in three groups were tested three times on four dependent variables. At 8 weeks the experimental group, after receiving the life review process, showed significant gains on two dependent variables, life satisfaction and psychological well-being, with analyses of covariance of F = 11.52, p less than .0001 and F = 9.90, p less than .003, respectively. Two other dependent variables, depression and activities of daily living, demonstrated no significant change at the 8 weeks posttest. Retesting 35 survivors at 1 year revealed little significant change for any group. There was, however, an upward trend in the experimental group on the outcome measure of life satisfaction and a downward trend in all groups on measures of activities of daily living and depression. PMID- 1512437 TI - Correlates of life satisfaction among elderly African Americans. AB - This study examined the correlates of Life Satisfaction among older African Americans. The sample consisted of 166 African Americans ranging in age from 65 to 88 years. There were 87 males and 79 females. Included as predictors of Life Satisfaction were self-rated health, self-perceived adequacy of income, weekly hours of participation in church activities, and family role involvement. The results of the study confirmed that family role involvement and participation in church activities were significant predictors of Life Satisfaction among African American elderly in general. Results also indicated significant sex differences. Females tended to manifest greater life satisfaction than males. Females also had higher mean scores on hours of church participation per week, scored higher on family role involvement, and were more likely than males to consider their incomes adequate. Therefore, separate correlation and regression analyses were run for male and female respondents. These analyses indicated that among males, family role involvement and hours of church participation were related significantly to life satisfaction, as were self-perceived adequacy of income, actual household income, educational level, and self-rated religiosity. Among females, only self-rated religiosity was a significant predictor of life satisfaction. This finding was attributed to the generally high levels of family role involvement and church participation among female respondents. PMID- 1512438 TI - Age-related changes in natural spontaneous fluid ingestion and thirst in humans. AB - Elderly humans have impaired responses to dehydration and overhydration when tested under experimental conditions. This study investigated whether under ad libitum conditions age-related changes in fluid intake and thirst could be detected. Adult humans (n = 262) maintained 7-day diaries of everything they ingested, the timing and conditions present, and subjective thirst, anxiety, depression, and activity. No differences were found in overall fluid intakes of subjects from 20 to 80 years of age, including equivalent fluid intake responses to solid food ingestion, subjective thirst, social stimuli, and stomach factors. However, fluid ingested in bouts increased slightly over the day for younger groups, whereas it declined markedly for elderly groups, producing a blunted diurnal rhythm. Also, elderly subjects ingested more coffee and less soda and alcohol. The findings indicate that elderly individuals, under ad libitum conditions, are able to obtain normal levels of fluid by the coingestion of fluids with solids. PMID- 1512439 TI - Cognitive slowing in Alzheimer's disease and geriatric depression. AB - Response slowing on psychological tasks is found both in Alzheimer's disease and depression. However, the underlying cause for this slowing may be different in the two disorders. This research examined whether the behavioral slowing found in Alzheimer patients results from a reduction in their rate of cognitive processing, whereas the slowing in depressed geriatric patients reflects a purely motor retardation. This hypothesis was tested using a task in which subjects had simply to determine the number of dots present in an array (i.e., enumeration). In all four subject groups (Alzheimer patients, depressed geriatric patients, healthy old controls, and healthy young controls), response time increased linearly with array size. The slope of this linear function (reflecting rate of enumeration) was the same in the normal and depressed patients, but was significantly greater in the Alzheimer patients, suggesting the presence of a cognitive slowing in Alzheimer's disease, but not in depression. PMID- 1512440 TI - Prospective memory intervention in Alzheimer's disease. AB - Four individuals with Alzheimer's disease were trained to remember and to implement an intention for future action. The training program utilized the spaced-retrieval method, which involves active attempts to recall information over expanding intervals of time. All participants learned to select a colored coupon from an array of distractors and offer it to the experimenter after a week's delay. Following one-week retention of the initial task, a different coupon became the new training target. All participants were able to shift to this new task requirement, and all learned three successive coupon colors successfully. These results indicate that individuals with Alzheimer's disease can learn a prospective memory task using spaced-retrieval practice and can make adjustments for changing task requirements. PMID- 1512441 TI - Impact of adult age and Alzheimer's disease on levels of neural noise for letter matching. AB - We tested healthy young and older adults as well as higher-scoring (Mini-Mental State Exam, MMSE, scores between 14-20) and lower-scoring patients diagnosed with probable Alzheimer's disease (AD) on a letter-matching task. Subjects were instructed to respond "same" if two simultaneously presented letters were identical, or "different" if the letters did not match. Healthy older adults showed a larger "fast-same" effect than healthy young adults. Also, higher scoring AD patients showed a large "false-different" effect for errors, but lower scoring AD patients showed a large "false-same" effect. These data indicate that older adults exhibit higher neural noise levels than younger adults. The cross over error pattern for AD suggests that moderately demented AD patients show evidence of forming degraded visual percepts whereas more severely demented AD patients show evidence of forming incomplete percepts. PMID- 1512442 TI - Adult age differences in the use of prosody for syntactic parsing and recall of spoken sentences. AB - In this experiment, young and elderly adults listened to and recalled sentences that were varied in speech rate through computer-controlled time compression. Half of the sentences at each speech rate were presented with a normal prosodic pattern that reinforced the lexically defined syntactic structure of the sentences, and half were presented with a prosodic contour that conflicted with that structure. Both young and elderly subjects showed better recall for slower speech rates and when prosody was consistent with syntactic structure, but these effects were larger for elderly subjects. When syntax and prosody were placed in conflict, elderly subjects were more likely than the young to reconstruct the lexical content of the presented sentences to produce responses with a syntactic structure consistent with the prosody marking. Although elderly adults may be disadvantaged by rapid speech input rates, we show that they rely on normal prosody to aid syntactic parsing as a step toward language comprehension. PMID- 1512443 TI - Educational attainment, occupational history, and stratification: determinants of later-life economic outcomes. AB - Determinants of economic well-being among men 25-44, 45-64, and 65+ were examined using data from the 1984 panel of the Survey of Income and Program Participation. A path analysis explored race, education, and occupational history effects on income adjusted for annuitized assets, household composition, and underreporting of unearned income. Direct and total education effects were undiminished among elderly persons, whose income derived mainly from benefits and assets, as compared with the nonelderly subjects whose income was dominated by earnings; education explained more of the variance in adjusted income for the elderly group than for the nonelderly. While Social Security income exerts an equalizing effect across educational attainment groups, private pensions and other important retirement income sources were highly education-dependent, producing a high overall degree of stratification on early-established socioeconomic characteristics. PMID- 1512444 TI - Racial and social correlates of age-related changes in functioning. AB - Six waves of observations spanning a decade on a panel of 566 Black and 5,196 non Black survivors were utilized to examine social and racial differences in age related changes in functioning. An index consisting of three dimensions was used to assess functioning: physical functioning, self-care capacity, and self-rated well-being. Growth curve analysis was used to assess variations in trajectories of functional impairment across Black/non-Black, poor/nonpoor, male/female, and high-school/non-high-school graduate subpanels. Trajectories vary across social groups in the expected manner. However, we note that the trajectories are not linear and that substantial variability exists within both the Black and non Black subpanels. Moreover, we note that Blacks report poorer functional status than non-Blacks even with income and education controlled. However, age changes do not differ across Black and non-Black subpanels, as predicted by the multiple jeopardy hypothesis. PMID- 1512445 TI - Are older people most afraid of crime? Reconsidering age differences in fear of victimization. AB - The reasons why previous studies of fear of crime yield different conclusions regarding age differences are examined. Data from a national survey of adults are used to assess whether older adults manifest the highest levels of fear of crime. No significant relationship was found between age and the commonly used indicators of fear of crime in many previous studies when controlling for relevant factors. Using an alternative strategy for measuring fear of crime- based upon rating fear for 10 different victimizations--reveals that younger persons are more likely than older persons to be afraid of most types of crime. Women score higher on fear for all victimizations considered. A LISREL analysis indicates that the 10 victimizations are best characterized as either personal or property crime and that older adults' scores on these dimensions are below the grand mean; persons 75 years or older have the lowest scores on fear of property crime. These results question the existence of the "victimization/fear paradox." PMID- 1512446 TI - An analysis of physician utilization by elderly persons: systematic differences between self-report and archival information. AB - Elderly persons may over- or underreport their utilization of services, and systematic variance in this discrepancy may bias research findings. Therefore, this study analyzed the discrepancy between archival and self-report measures of physician utilization and examined the association of that discrepancy with health status and sociodemographic variables. Each older person underreported physician utilization by a net of .35 visits, but the total discrepancy was nearly two visits per person, or 65 percent of the number of self-reported visits. The multivariate findings indicate that underreports of utilization are smaller for those elderly persons with lower health status (as measured by disease history) and larger for those with higher levels of utilization. Those in poor health tend to overreport physician visits, and those with greater levels of utilization tend to have greater proportional reporting error. Self-reported measures of physician utilization should be considered in the context of the net error and the systematic nature of that error. PMID- 1512447 TI - Health and geographic mobility among the recently widowed. AB - The death of a spouse has been described as the most disruptive and difficult role transition that an individual confronts throughout the life course. Using data from the 1984 and 1986 waves of the Longitudinal Study of Aging conducted by the National Center for Health Statistics, we examined the probability of moving associated with changes in functional disability levels over a two-year period while controlling for recent widowhood. We found that the greater the increase in instrumental disability between 1984 and 1986, the greater the probability of a move. We also found that the event of becoming a widow greatly increases the probability of a move when health declines. PMID- 1512448 TI - Epidemiological analysis of Klebsiella infections at a neonate department. AB - At the Department of Obstetrics and Gynaecology of a Brno hospital, 133 Klebsiella strains were isolated from 23 mothers and 58 neonates during a period of increased incidence of Klebsiella and 73 strains were examined in the laboratory. The control group was comprised by 78 Klebsiella strains isolated at three other Brno hospitals. Four prevailing Klebsiella types were identified using bacteriocinotyping and phagotyping. Different bacteriocinotypes and phagotypes were found to prevail at certain intervals both at the examined clinic and in control patients from Brno hospitals. The findings suggest circulation of certain Klebsiella types and their introduction to hospitals. Most infants (37 out of 45, i.e. 82%) were colonized by Klebsiella, their mothers remaining without colonization. The factors influencing the onset and transmission of nosocomial infections in infants are discussed. PMID- 1512449 TI - The incidence of conditionally pathogenic mycobacteria in the northern Moravia region in 1978-1987. AB - The incidence of potential pathogenic mycobacteria (PPM) has been studied in the Northern Moravia since 1970. The present paper follows up a previous communication summing up the finding for the period 1970-1977 during which were isolated from 713 persons. In 1978-1987, 4,658 strains were isolated from 1,917 persons. The species most frequently isolated was M. gordonae. A significant increase was observed in the incidence of mycobacterioses due to M. kansasii, namely from 2.90/100,000 in 1970 to 17.70/100,000 in 1987 in the Karvina district, the centre of endemic area. PPM was isolated from 321 water samples. PMID- 1512450 TI - Onchocerciasis in Plateau State; Nigeria: ecological background, local disease perception & treatment; and vector/parasite dynamics. AB - The physico-biological ecological complex in Plateau State has by definition increased the potential of most rivers to support the breeding and dispersal of vector species as well as human acquisition and dissemination of the disease for several months in a year. Though villagers in endemic areas are of the know of the nuisance of blackfly bites, but the majority of them lacked the aetiological knowledge of onchocercal lesion. Hence disease management is misdirected towards consulting the oracle and appeasing the gods. The vectors of onchocerciasis in Plateau State, S. damnosum, and S. sirbanum are wet season breeders with their peak biting density occurring at the height of rainy season. However, biting flies carry more infective parasites at the beginning and end of rain. These vectors exhibit bimodal biting activity: a small one in the morning hours and a pronounced evening peak. Biting activity is at least influenced by two major climatic factors; illumination and temperature. However, the fastest changing climatic factor relative to an increase in the biting activity of flies was illumination. Microfilarial load in the skin of patients does not significantly change throughout the year or when biopsies are taken under shade throughout the day. Extreme temperatures, however, have significant reducing effect on the skin microfilarial. The epidemiological relevance of these in the ongoing MECTIZAN delivery in the State are discussed. PMID- 1512451 TI - Human ecology and parasitic infections. 1. The effect of occupation on the prevalence of parasitic infections in Calabar, Nigeria. AB - One thousand six hundred people belonging to three different occupational groups were randomly selected. Blood, urine and stool specimens were collected from them and processed for the detection of any parasitic infections. The results show 28.5% infection rate with one or more species of intestinal parasites; 50.7% in the school children, 17.3% among the farmers, and 12% among the soldiers. Results of blood examination showed 5.3%, 8.0% and 2.0% infection rates for P. falciparum in the school pupils, farmers and soldiers respectively, while 31.3% of the three groups were infected with the microfilaria of Dipetalonema perstans, and Loa loa. These were found in 60.7% of the farmers and none at all in the other two groups. Urine examination yielded no positive cases of urinary schistosomiasis and only one case of Trichomonas vaginalis. These results reflect the endemicity of the respective parasites, the degree of their sanitary awareness and their exposure frequencies to the pathogens as a result of their daily activities. PMID- 1512452 TI - Field utility of phenolic glycolipid coated latex agglutination test for rapid detection of bacilliferous leprosy cases. AB - Serum samples were collected from eighty-three leprosy patients and twenty-five healthy controls supposedly not exposed to Mycobacterium leprae infection. Phenolic glycolipid-1 coated latex agglutination test (PGL-LAT) was carried out with the serum samples to detect antibodies specific to M. leprae. Samples showing positive agglutination were 50% in the lepromatous leprosy (LL) group showing no erythema nodosum leprosum (ENL) complications, 66.6% in LL group with ENL complication, 60% in borderline lepromatous (BL) group, 50% in borderline (BB) and 33.3% in borderline tuberculoid (BT). The patients belonging to the tuberculoid (TT) group and most of the long-term treated patients were interestingly negative, and so were sera from all the healthy controls. PGL-LAT developed by us therefore is specific and a fairly sensitive technique to detect antibodies specific to M. leprae and will be very useful in field conditions. PMID- 1512453 TI - Eosinophilia in murine ancylostomiasis. AB - Eosinophil changes in the peripheral blood of singly and repeated infected mice were studied during murine ancylostomiasis. In singly infected animals, eosinophils began to rise on 1st day, reached a peak on 4th day and progressively declined from 9th to 30th day. In repeatedly infected animals, peak eosinophilia was observed during 3rd week of post infection and sustained upto 30th day with a slight decrease. These studies demonstrate that eosinophilia is induced due to antigen-antibody reactions in the host system and eosinophilia in helminthic infections is amnestic response. PMID- 1512454 TI - Evaluation of enzyme linked immunosorbent--assay for the detection of anticysticercus antibodies in cerebrospinal fluid from patients with neurocysticercosis. AB - Enzyme linked Immunosorbent Assay (ELISA) was done for the detection of antibodies to Cysticercus cellulosae in 135 cerebrospinal fluid (CSF) and 152 serum samples from patients suspected clinically of neurocysticercosis (NC), neurological disorders other than NC and controls by the use of crude cyst extract antigen. This assay was compared with the standard technique of indirect haemagglutination test (IHA). The results of the two techniques were matched with retrospective analysis of proven diagnosis of these patients. ELISA and IHA was found to be positive respectively in 88 and 84 percent of CSF and 92 and 87.2 percent of serum samples from proven NC patients. The IHA technique was found to be absolutely specific for the detection of antibodies in CSF samples while cross reactions were observed with ELISA technique in CSF from 5 patients, one each suffering from disappearing CT scan lesion, tubercular meningitis (culture negative), chronic meningitis, benign intracranial hypertension and non compressive myelopathy. However possibility of neurocysticercosis cannot be absolutely ruled out in such patients. Both the techniques were found to be highly non specific for the detection of antibodies in serum samples. The study suggests that either of the two techniques may be used for the detection of antibodies in CSF samples from clinically suspected NC patients with high degree of sensitivity and specificity. PMID- 1512455 TI - The in vitro and in vivo effects of mefloquine on Trypanosoma brucei brucei. AB - Blood stream forms of Trypanosoma brucei brucei were grown over mouse kidney (MK) cells in minimum essential medium with various concentrations of mefloquine. The drug was observed to inhibit multiplication of the parasites in vitro. Groups of male albino mice were treated with mefloquine at 24, 48 and hours after T. b. brucei infection. Mefloquine at 0.03 mg/kg body weight administered for 4 consecutive days cleared the infection. No trypanosomes were detected in the blood of these mice for 90 days and over after the clearance of parasite from the blood. The doses for both the in vitro and in vivo therapy, were well below those prescribed for humans. PMID- 1512456 TI - Respiratory burst metabolic status of macrophages in experimental leprosy. AB - Peritoneal macrophages from uninfected controls and Mycobacterium leprae infected Swiss albino mice were studied for their respiratory burst (RB) activity at different time intervals. The RB metabolic activity of macrophages declined significantly after 3 month infection using latex (p less than 0.001) and M. leprae (p less than 0.01) as stimuli. However, significant rise (p less than 0.001) in the oxidative metabolic activity was seen at 6 and 9 months postinfection period on stimulation with both the stimuli. The sharp rise in the oxidative metabolic status at peak period of infection in the experimental animals suggests that the macrophages are functionally normal though M. leprae is unable to trigger the respiratory burst sufficiently. PMID- 1512457 TI - Classification of strains of Pragia fontium, Budvicia aquatica and of Leminorella by whole-cell protein pattern. AB - SDS PAGE protein patterns of 37 H2S-positive strains of species belonging to the family Enterobacteriaceae including the genera Budvicia (11 strains) and Leminorella (L. grimontii--3 strains, L. richardii--4 strains) were compared with 10 strains of species Pragia fontium. All strains under study form well separated clusters with overall similarity C = .49. Clusters are separated in the range of C = .68-.83. They display high homogeneity, only one strain of Edwardsiella tarda clusters with budviciae. Strains of Pragia form two distinct clusters separated from other genera. Electrophoretograms of two strains which do not group as expected are analyzed and results discussed. Results support evidence that strains designated Pragia fontium deserve independent treatment as a new species. PMID- 1512458 TI - Interactions between heterochronic cells in the formation of delayed-type hypersensitivity. AB - The effect of ageing on lymphocyte and macrophage functional activity in the induction of tuberculin sensitivity was studied in experiments on 440 CBA mice of three age groups. The capacity of old animals to generate delayed-type hypersensitivity following administration of BCG cells was found to be diminished and their lymphocytes caused decreased hypersensitivity on transplantation. The capacity of recipients to reproduce delayed-type hypersensitivity after thymocyte and bone marrow cell transplantation was influenced by the age of transplanted thymocytes. This capacity was markedly suppressed on the recipients of old cells. The antigen presentation function of macrophage did not after significantly as a function of age. PMID- 1512459 TI - Clinical, histologic, and immunofluorescent distinctions between subacute cutaneous lupus erythematosus and discoid lupus erythematosus. AB - Subacute cutaneous lupus erythematosus (SCLE) was originally described and distinguished from discoid lupus erythematosus (DLE) on the basis of clinical examination of the skin, but subsequent reports have questioned the concept of SCLE as a marker of a unique subset of LE patients. We classified 27 lupus patients, on the basis of cutaneous exam, as having discoid lupus skin lesions, subacute cutaneous skin lesions, or systemic lupus erythematosus (SLE) without DLE or SCLE lesions. Clinical features most characteristic of SCLE rather than DLE were superficial, non-indurated, non-scarring lesions, and photosensitivity, with lack of induration being the single most helpful finding. Histologic examination of lesional skin showed a relatively sparse, superficial infiltrate in SCLE and a denser, deeper infiltrate in DLE. A distinctive pattern of staining with direct immunofluorescence, particulate epidermal IgG deposition, was found in seven of seven SCLE patients (all anti-Ro/SSA positive) and none of the other patients. This distinctive pattern can be reproduced experimentally when anti Ro/SSA autoantibodies are infused into human skin-grafted mice. Particulate dermal-epidermal junctional staining was the pattern seen in the patients who did not have SCLE. Clinically defining SCLE as a superficial inflammatory form of cutaneous lupus (i.e., considering lesions to be DLE if they are indurated) results in a meaningful segregation of SCLE and DLE patient groups. The epidermal IgG deposits unique to SCLE provide independent evidence that the clinical findings that were used to identify the patient groups actually identify distinctive cutaneous lupus subsets. The observation that antibodies are present in a different location in the skin in SCLE than in DLE indicates that SCLE and DLE are likely to have different pathomechanisms. PMID- 1512460 TI - Cloning of partial cDNA for mouse 180-kDa bullous pemphigoid antigen (BPAG2), a highly conserved collagenous protein of the cutaneous basement membrane zone. AB - One-hundred-eighty kilodalton bullous pemphigoid antigen (BPAG2) is recognized by autoantibodies in the sera of patients with blistering skin diseases, bullous pemphigoid (BP), and herpes gestationis (HG). In this study, we have screened a mouse epidermal keratinocyte cDNA library with a 1.0-kb human BPAG2 cDNA, which has been shown to correspond to two collagenous domains (Giudice et al: J Clin Invest 87:734-738, 1991). Screening of the mouse library identified two cDNA clones, the larger one being 1.8 kb in size. Comparison of the mouse amino acid sequences, as deduced from cDNA, with the corresponding human sequences revealed 86% homology. Furthermore, Northern hybridizations of mouse epidermal RNA with these cDNA revealed the presence of an mRNA transcript of approximately 6 kb, the size of the human BPAG2 mRNA. Elucidation of the deduced amino-acid sequences revealed the presence of definitely one and possibly two putative membrane associated segments, suggesting that the 180-kDa BP antigen is a transmembrane protein. The sequence analysis also identified a 7-amino-acid segment that was predicted by computer analysis to be antigenic. Elucidation of the divergence between the mouse and previously published human and chicken BPAG2 sequences indicated that this protein segment was relatively well conserved. These data suggest, therefore, that the 180-kDa bullous pemphigoid antigen associated with hemidesmosomes is a well-conserved transmembrane protein that may play a critical role in the attachment of epidermis to the underlying basement membrane. PMID- 1512461 TI - Cytoplasmic domain of the 180-kD bullous pemphigoid antigen, a hemidesmosomal component: molecular and cell biologic characterization. AB - Using a serum sample of a bullous pemphigoid (BP) patient we have isolated a cDNA clone encoding a portion of a 180-kD polypeptide component of the hemidesmosome, the "BP180 autoantigen." The identity of the clone was confirmed by the generation of a fusion protein antibody that recognizes BP180 in both a basal epithelial cell extract of bovine tongue and extracts of human epidermal cells. Immunoelectron microscopy indicates that the 588-bp cDNA encodes a cytoplasmic fragment of BP180. Furthermore, the wide species reactivity of the fusion protein suggests that this portion of BP180 is highly conserved. In cultured human epidermal cells processed for confocal immunofluorescence microscopy, the fusion protein antibody generates a punctate cell substrate-associated staining pattern that is similar to that seen using BP230 antibodies. Using the original BP180 cDNA we have now isolated additional cDNA clones encoding approximately 1800bp of BP180 the 3' sequence of which overlaps with the sequence detailed in Guidice et al (J Clin Invest 87:734-738, 1991). Secondary structural analyses have been undertaken on the predicted amino acids encoded by the 1800bp. These suggest that the collagen-like sequences of BP180 described by Guidice et al (ibid.) are separated by a putative transmembrane region from the domain of BP180 recognized by our fusion protein antibody. Indeed, BP180 appears to belong to a relatively rare group of proteins in which the N-terminus is located in the cytoplasm and the C-terminus is extracellular. We detail some preliminary biochemical experiments in support of this hypothesis. We discuss possible functions of BP180 and BP230 in the hemidesmosome. PMID- 1512462 TI - Isolation of human immunodeficiency virus type 1 from human epidermis: virus replication and transmission studies. AB - For a better understanding of the pathogenetic events operative in the cutaneous manifestations of human immunodeficiency virus type 1 (HIV-1) disease, we investigated whether epidermal cells (EC) from HIV-1-seronegative persons can be infected with HIV-1 and, vice versa, whether HIV-1 can be rescued from the epidermis of HIV-1-infected individuals. In a series of three experiments, we consistently found that exposure of EC from HIV-1-seronegative donors to HIV-1 led to viral replication in these cells as evidenced by the detection of HIV-1 p24 in culture fluids. Because EC had been substantially enriched for Langerhans cells (LC) before being exposed to HIV-1, it is reasonable to assume that these CD1a+/CD4+/MHC class II+ antigen-presenting cells of the epidermis represented the actual targets of infection. This assumption is further strengthened by the observation that T cell-depleted cell suspensions from Langerhans cell histiocytosis (LCH) lesions could be productively infected with HIV-1. Conversely, co-culture of epidermal sheets from HIV-1-seropositive individuals with mononuclear phagocytes (MNP) from HIV-1-seronegative donors resulted, after 3 to 5 weeks, in the detection of HIV-1 p24 in 12 of 23 cases. Immunocytochemical analysis, using a monoclonal antibody specific for p24, revealed the presence of HIV-1 in adherent MNP in three cocultures tested. In addition, cellular DNA from these cultures showed strong signals when hybridized to a HIV-1-specific DNA probe. The further finding that two isolates examined exhibited different restriction enzyme patterns indicates that they are separate entities rather than contaminants. Transmission of these isolates to MNP, B- or T-cell lines resulted in cultures strongly positive for p24 and, in the case of H9 cells, for viral particles as detected by electron microscopy. Our results therefore strongly suggest that EC not only can serve as targets for HIV-1, but also can allow efficient virus replication and transmit HIV-1 to various cell types of the hematopoietic lineage. PMID- 1512463 TI - Role of intercellular lipids in stratum corneum in the percutaneous permeation of drugs. AB - The effect of the depletion of intercellular lipids from human stratum corneum and shed snake skin on the permeability to salicylic acid (SA) was investigated in vitro. Shed snake skin was used as a model membrane for human stratum corneum. Lipid depletion with a mixture of chloroform and methanol increased the permeability of those skins to the ionized form but not to the unionized form of SA. Moreover, lipid depletion increased dramatically the permeability of shed snake skin to compounds with low lipophilicity, although it did not have a significant effect on the more lipophilic compounds. As a hypothesis to explain the marked increase of skin permeability to compounds of low lipophilicity, including the ionized form of SA, we suggest increased water transport. PMID- 1512464 TI - Melanoma cytotoxicity of buthionine sulfoximine (BSO) alone and in combination with 3,4-dihydroxybenzylamine and melphalan. AB - Buthionine sulfoximine (BSO), a specific inhibitor of glutathione synthesis, showed variable growth-inhibitory activity in different tumor cell lines with a high degree of inhibitory activity against melanoma-derived cell lines. A correlation between BSO growth-inhibitory effects and cellular glutathione peroxidase activity was observed. In contrast, no correlation was demonstrated between the response to BSO and cellular tyrosinase, gamma-glutamylcysteine synthetase, glutathione transferase, gamma-glutamyl transpeptidase, or glutathione reductase activities. BSO enhanced 3,4-dihydroxybenzylamine (3,4 DHBA) (fourfold) and melphalan (threefold) in vitro cytotoxic activity as determined by inhibition of DNA synthesis in human melanoma cells and this enhancement was dependent on the duration of exposure to drug. BSO demonstrated in vivo antitumor activity in B16 melanoma-bearing mice prolonging survival by 29% and in combination with 3,4-DHBA resulted in a slight (48% versus 38%) increase in life span as compared to 3,4-DHBA alone. The combination of BSO and melphalan, however, increased the life span of B16 melanoma-bearing mice by 170%, as compared to melphalan alone (80%). These studies demonstrate a unique in vivo antimelanoma activity of BSO. PMID- 1512465 TI - Interleukin-8 stimulates calcium transients and promotes epidermal cell proliferation. AB - The presence of large amounts of biologically active interleukin-8 (IL-8) in psoriatic involved skin suggests that it may contribute, in part, to the changes observed in psoriasis, including hyperproliferation of keratinocytes. To examine the effect of IL-8 on epidermal growth, we monitored cytosolic free Ca++ transients in human keratinocytes adult skin epidermis calcium reduced level, temperature elevated (HaCat) cells and normal keratinocytes loaded with the cell permeable, acetoxymethyl derivative, indo-1AM. Addition of IL-8 (0.06-47 nM) to the HaCat cells induced rapid rises in cytosolic free Ca++ from resting levels of 145 +/- 38 to peak levels of 889 +/- 10 nM. The induced rises in Ca++ were transient and concentration dependent. Half maximal effect was observed at 1.2 nM. Normal keratinocytes also responded to IL-8 (6 nM) by rises in cytosolic free Ca++ from a pre-stimulated level of 269 nM to transient peak value of 393 nM. In addition, IL-8 promoted epidermal cell proliferation. Polyclonal anti-IL-8 antibody blocked IL-8-induced calcium changes and proliferation. Under similar conditions, human neutrophils also responded to IL-8 in a similar dose range by a rapid and transient mobilization of Ca++. The findings indicate that IL-8 has a wider range of responsive target cells than hitherto thought and acts as an autocrine growth factor. PMID- 1512466 TI - Molecular cloning and expression of a novel keratinocyte protein (psoriasis associated fatty acid-binding protein [PA-FABP]) that is highly up-regulated in psoriatic skin and that shares similarity to fatty acid-binding proteins. AB - Analysis by means of two-dimensional (2D) gel electrophoresis of the protein patterns of normal and psoriatic unfractionated non-cultured keratinocytes has revealed a few low-molecular-weight proteins that are highly up-regulated in psoriatic skin. These include psoriasin; calgranulin B, also known as MRP 14, L1, or calprotectin; calgranulin A or MRP 8; and cystatin A or stefin A. Here, we have cloned and sequenced the cDNA (clone 1592) encoding a new member of this group of low-molecular-weight proteins [isoelectric focusing (IEF) SSP 3007 in the keratinocyte 2D gel protein database] that we have termed PA-FABP (psoriasis associated fatty acid-binding protein). The deduced sequence predicted a protein with molecular weight of 15,164 daltons and a calculated pI of 6.96, values that are close to those recorded in the keratinocyte 2D gel protein database. The protein comigrated with PA-FABP as determined by 2D gel analysis of [35S] methionine-labeled proteins expressed by transformed human amnion (AMA) cells transfected with clone 1592 using the vaccinia virus expression system and reacted with a rabbit polyclonal antibody raised against 2D gel purified PA-FABP. Structural analysis of the amino acid sequence revealed 48%, 52%, and 56% identity to known low-molecular-weight fatty acid-binding proteins belonging to the FABP family. Northern blot analysis showed that PA-FABP mRNA is indeed highly up-regulated in psoriatic keratinocytes. The transcript is present in human cell lines of epithelial and lymphoid (Molt 4) origin but cannot be detected in normal or SV40 transformed MRC-5 fibroblasts. 2D gel protein analysis of normal primary keratinocytes cultured for at least 8 d under conditions that promoted incomplete terminal differentiation [serum-free keratinocyte (SFK) medium supplemented with epidermal growth factor (EGF), pituitary extract, and 10% fetal calf serum] revealed a strong up-regulation of PA-FABP, psoriasin, calgranulins A and B, and a few other proteins that are highly expressed in psoriatic skin. The levels of these proteins exceeded by far those observed in non-cultured normal keratinocytes implying that the cultured cells have followed an altered pattern of differentiation that resembles--at least in part--that of non-cultured psoriatic keratinocytes. The implications of these results for the study of psoriasis are discussed. PMID- 1512468 TI - Cutaneous blood flow in gestational hypertension and normal pregnancy. AB - A laser Doppler flowmeter was used to assess skin blood flow changes in three groups of young subjects: women with gestational hypertension, healthy pregnant women, and healthy non-pregnant women. Responses to four vasoactive stimuli were studied: isometric and cognitive activities, cutaneous post ischemic reactive hyperemia, and local heating. The first two stimuli are vasoconstrictive and were performed on the fingertip, whereas the latter two are vasodilative and were performed on the forearm. The most prominent differences were observed in the isometric test, where the expected decrease, which was indeed registered in non pregnant women, was almost absent in the healthy pregnant group. The gestational hypertension group had a greater decrease in blood flow than normal pregnancy, but lesser than non-pregnant control subjects. We conclude that although normal pregnancy modifies the response of the skin microvasculature to some vasoactive stimuli, gestational hypertension pushes that response back toward the non pregnancy state. PMID- 1512467 TI - Lesional elastase activity in psoriasis, contact dermatitis, and atopic dermatitis. AB - Human leukocyte elastase (HLE) is a broad spectrum serine protease derived from neutrophils and macrophages. We developed an assay to determine HLE activity on the skin surface in patients with inflammatory skin diseases. HLE activity was absent in the skin of healthy controls. A massive increase of HLE activity was found in lesional skin of psoriasis (31 times), allergic contact dermatitis (55 times), and atopic dermatitis (35 times), but not in uninvolved skin of diseased patients. Therefore, this assay appears to represent a useful biochemical marker of epidermal inflammation. The presence of proteolytically active HLE in diseased epidermis, which is known to contain specific inhibitors of this enzyme, suggests a pathophysiologic role of this enzymatic activity in psoriasis, contact dermatitis, and atopic dermatitis. PMID- 1512469 TI - Immunomorphologic and biochemical identification of the pemphigus foliaceous autoantigen within desmosomes. AB - Desmosomes are specialized domains of the plasma membrane that play a fundamental role in intercellular adhesion. This adhesive function is mediated at least in part by the cadherin homologous cell adhesion molecule (CAM) desmoglein (dg). Autoantibodies (aab) from patients with pemphigus foliaceous (pf), a blistering disease of the epidermis, have been shown by immunochemical methods to bind to desmoglein. However, the molecular localization of the binding sites of these antibodies, especially as it relates to the ultrastructure of the desmosomes, has not been definitively characterized. We therefore performed pre-embedding direct immunoelectron microscopy (IEM) on perilesional skin of patients with pf and post embedding indirect IEM using sera from five patients with pf. We first confirmed by immunoprecipitation and immunoblotting that these sera bound dg. Both IEM methods showed that pf-aab exclusively bind to desmosomes. Double-labeling IEM of several other constitutive desmosomal proteins further suggests that most likely pf-aab bind to an extracellular domain of the transmembrane CAM dg. Our studies suggest one possible pathophysiologic mechanism for the clinical manifestations of pf: namely, that the binding of aab to an extracellular epitope of desmoglein might impair the adhesive properties of desmosomes mediated by dg and result in the loss of cell adhesion leading to acantholysis and blister formation. PMID- 1512470 TI - Cultured human Langerhans cells process and present intact protein antigens. AB - Epidermal Langerhans cells (LC) undergo profound phenotypic and functional alterations when cultured for 2 to 3 d. To determine whether the in vitro culture of human LC modulates their capacity to process and present intact protein antigens, we compared the ability of freshly isolated LC (fLC) and cultured LC (cLC) to stimulate in vitro T-cell proliferative responses to recall antigens. We found that human fLC and cLC were able to process and present recall antigens to primed T cells, inducing significant proliferative responses. For tetanus toxoid and Candida albicans extract, T-cell proliferative responses at 6 d to antigen pulsed fLC were slightly greater than responses to antigen-pulsed cLC. For live influenza A virus, the T-cell responses induced by antigen-pulsed cLC were comparable or slightly greater compared with fLC. Allogeneic T-cell proliferation for both LC preparations were also comparable. The exogenous pathway of antigen processing was demonstrated by chloroquine inhibition. PMID- 1512471 TI - Relaxin alone and in conjunction with interferon-gamma decreases collagen synthesis by cultured human scleroderma fibroblasts. AB - Fibroblasts derived from the involved skin of scleroderma patients frequently display a phenotype of supernormal collagen expression when cultured. Fibroblasts displaying this phenotype derived from seven patients were treated with relaxin (1-100 ng/ml) and interferon-gamma (1-100 U/ml), individually and in combination, to assess the relative abilities of these cytokines to down-modulate collagen synthesis and secretion. Scleroderma fibroblasts displayed varying sensitivities to both relaxin and interferon-gamma. Relaxin (100 ng/ml) decreased expression of collagen by six of seven lines tested from 8 to 59% compared to untreated cultures. Interferon-gamma (100 U/ml) depressed collagen secretion by all seven lines in a range from 7 to 89%. When relaxin and interferon-gamma were used in combination, relaxin augmented IFN-gamma-induced decreases in collagen secretion in four of seven lines. In three of these lines, the use of relaxin in conjunction with suboptimal doses of interferon-gamma resulted in decreases equivalent to or greater than that seen with a tenfold higher concentration of interferon-gamma. This study demonstrates the ability of relaxin to directly alter the excessive collagen-producing phenotype of scleroderma fibroblasts. In addition, in some cases, combining relaxin and interferon-gamma resulted in a cooperative effect in decreasing collagen expression by scleroderma cells in vitro. PMID- 1512472 TI - Cytokine-induced expression of transforming growth factor-alpha and the epidermal growth factor receptor in neonatal skin explants. AB - Hyperproliferative diseases of the epidermal keratinocytes, such as psoriasis vulgaris, are characterized by overexpression and altered distribution of the epidermal growth factor/transforming growth factor (EGF/TGF)-alpha receptor, and of TGF-alpha itself. It is believed that overexpression of this lignad/receptor system contributes to the hyperproliferative state of keratinocytes in an autocrine fashion. However, little is known about the factors that regulate expression of the EGF/TGF-alpha receptor, as well as expression of TGF-alpha in stratified epithelium. We examined modulation of the immunoreactive EGF/TGF-alpha receptor and TGF-alpha expression in normal neonatal foreskin explants by a variety of cytokines present in psoriatic lesions. Human (hu) recombinant (r) tumor necrosis factor (TNF)-alpha and interferon (IFN)-gamma induced EGF/TGF alpha receptor and TGF-alpha expression by keratinocytes as determined by immunohistochemistry. Neutralizing antibodies to TNF-alpha and IFN-gamma inhibited upregulation of EGF/TGF-alpha receptors and TGF-alpha by the respective cytokines. Interleukin (IL)-8 induced expression of TGF-alpha, but not of its receptor. Other cytokines (TNF-beta, IFN-beta, IL-1 alpha, IL-2, IL-3, IL-5, IL 6, granulocyte/macrophage colony-stimulating factor, and macrophage colony stimulating factor) did not alter the expression patterns of EGF/TGF-alpha receptors or TGF-alpha in normal neonatal skin explants. These experiments demonstrate that specific cytokines known to be present in psoriatic lesions can induce normal epidermis to express TGF-alpha and its receptor in a pattern similar to that observed in psoriatic skin. PMID- 1512473 TI - Microdialysis of the interstitial water space in human skin in vivo: quantitative measurement of cutaneous glucose concentrations. AB - The purpose of this study was to evaluate the usefulness of a microdialysis technique for measurement of substances in the interstitial water space in intact human skin. Glucose was selected to validate the method. The cutaneous glucose concentration was measured by microdialysis and compared to that in venous blood. Single dialysis fibers (length 20 mm, 2,000 Da molecular weight cutoff) were glued to nylon tubings and inserted in forearm skin by means of a fine needle. Dialysis fibers were inserted in duplicate. Seven subjects were investigated after an overnight fast. Intradermal position of the dialysis probes was established by C-mode ultrasound scanning. The implantation trauma lasted 90-135 min as measured by laser Doppler flowmetry. Each dialysis fiber was calibrated in vivo by perfusing it with four to five different glucose concentrations. The perfusion rate was 3 microliters/min. Regression analysis of the calibration curves yielded the relative in vivo recovery of glucose. The skin glucose concentration was calculated as that particular perfusate glucose concentration that resulted in no net glucose transport across the dialysis membrane. Correlation coefficient of the regression lines was 0.93 +/- 0.03 (mean +/- SEM). After the injection trauma had vanished, recovery was 20.5 +/- 0.7%. Coefficient of variation (CV) on recovery was 10.9%. The cutaneous glucose concentration was 99.1 +/- 1.8% of the glucose concentration in venous plasma water (CV 4.1%). These findings suggest that the microdialysis technique accurately and precisely can reflect biochemical events in the interstitial water space in human skin in vivo. PMID- 1512474 TI - [Radiological follow-up of motion in the cervical spine after surgery]. AB - The influence of cervical spine in motion after surgery was evaluated by preoperative and postoperative functional radiography. Based on the analysis of postoperative radiograms, the following results were obtained: (1) The motion of cervical spine segments adjacent to the level of the anterior interbody fusion was increased after surgery. The larger the number of fused vertebral bodies, the greater the motion of the adjacent segments. A larger number of anterior fused vertebral bodies may cause more future damage to adjacent intervertebral discs. (2) The motion of the cervical spine was decreased after posterior procedures, especially laminoplasty, which preserves the posterior element. (3) Tilting motion and lordosis of the C 1/2 level was increased after anterior interbody fusion, laminectomy and laminoplasty. PMID- 1512475 TI - [The influence of soft tissue contractures on the walking ability of patients with spastic cerebral palsy]. AB - The influence of soft tissue contractures on walking ability was investigated in 73 patients with spastic cerebral palsy. The relationship between the degree of soft tissue contractures and ambulation level was analyzed using Hayashi's quantification theory type II. The walking energy expenditure and electromyography magnitude (E.M.G. magnitude) were also measured in 11 patients who could walk on treadmill. Hayashi's quantification theory type II showed a significant correlation between the degree of soft tissue contractures and ambulation level. Both energy expenditure and E.M.G. magnitude were found to be significantly higher than in normal subjects. The levels increased in relation to walking speed. A significant correlation between walking energy expenditure and the degree of soft tissue contractures was found using multiple regression analysis. From these results, it was concluded that the soft tissue contractures had a strong influence on ambulation level and walking energy expenditure in spastic cerebral palsy. PMID- 1512476 TI - [Force measurement of reconstructed anterior cruciate ligament in relation to changes in length in experiments using cadaver knees]. AB - The effects of tibial and femoral attachment sites on changes in length and force were investigated in ACL grafts, using eight cadaver knees. Two tibial and three femoral attachment sites were chosen, such as the anteromedial and central sites in the tibial insertion of the ACL, and the central and anterior-superior sites in the femoral insertion, as well as the over-the-top route. Changes in the length in all combinations of these attachment sites was measured from extension to 150 degrees flexion at 15 degrees intervals by the displacement of a cord 2 mm in diameter which simulated the graft. The holes through the attachment sites were then enlarged to accept a 6 mm wide LAD (Ligament Augmentation Device, 3M). The force in this LAD graft was measured over the same range of knee flexion using a buckle transducer for all combinations of sites. Changes in length and force were affected more by the femoral attachment site. There was a close correlation between length changes and force measurements except at a neighborhood of the full extension. Changes in force between a given combination of sites failed to show a reproducible pattern among the knees tested. PMID- 1512477 TI - [Assessment of limp in patients with coxarthrosis--three-dimensional measurement of the pelvic rotation]. AB - To assess the gait characteristics of the patients with coxarthrosis objectively, the rotation of the pelvis during ambulation was measured on the frontal, sagittal and horizontal planes using 3 gas-rate-sensors(Rotational Angle Measurement System G-2210, Anima Inc., Tokyo). In the normal subjects, the waveforms of the rotational angle on the frontal plane were symmetrical, highly reproducible and had 2 peaks. In contrast, the waveforms of the patients were asymmetrical and poorly reproducible. This was shown objectively using Fourier transform technique. The mean rotational angle of the patients was smaller than that of the normal subjects on the frontal plane, and larger on the sagittal plane. We can distinguish the patients from the normal subjects by observation of the waveform on the frontal plane and the ratio of the rotational angle on the sagittal plane to that on the frontal plane. PMID- 1512478 TI - [Isokinetic torque of the knee extensor and flexor in patients with recurrent patellar dislocation]. AB - In order to establish the role of muscle strength in the recurrent dislocation of the patella, an isokinetic study was performed using BIODEX, by which the concentric (CC) and passive eccentric (PEC) torques of the quadriceps and hamstrings were measured. The angle velocity was set at 30 degrees and 90 degrees/sec. The subjects were divided into three groups: (I) non-surgical, (II) surgical and (III) normal control. In each group 20 knees were tested, and the following results were obtained. 1. Peak torque: At either 30 degrees/sec or 90 degrees/sec of velocity, it was significantly smaller in group I. On the other hand, the torque in group II was similar to that of group III. 2. E/C (eccentric torque/concentric torque) ratio: PEC was divided by CC to express a muscular strength balance. At 30 degrees/sec velocity, group I showed a significantly high E/C ratio. CONCLUSION: The knees with recurrent dislocation of the patella exhibited significantly lower peak torque and irregular curve patterns. The muscle strength, has been restored to a near-normal level in the surgical group, therefore, the muscle weakness in this disorder can be considered to be a secondary factor. The eccentric torque appeared to play a major role in the development of recurrent dislocation of the patella. PMID- 1512480 TI - [Analysis of three-dimensional motion of the scapula and the glenohumeral joint]. AB - Three dimensional motion of the scapula and the glenohumeral joint was measured and analysed during flexion, elevation in the scapular plane, and abduction using a three space tracker system. The downward tilting angle of the glenoid cavity was at an angle of -20 degrees during motion. The medially tilting angle of the glenoid cavity changed in a different manner in a different plane of elevation. The angle of elevation of the glenoid cavity changed from -12.6 degrees to 27 degrees in all planes. Elevation of the glenoid cavity and movement of the scapula in parallel were analyzed. During flexion the glenoid cavity faced the plane of flexion and stabilized the glenohumeral joint. During abduction the glenoid cavity moved as though slipping off from the glenohumeral joint. The total of the angles of elevation of the glenoid cavity and the glenohumeral joint did not always equal the angle of elevation of the arm. PMID- 1512479 TI - [Electron microscopic and immunohistochemical studies on chondroblastoma]. AB - Six clinically and patho-histologically proven cases of chondroblastoma were studied with electron microscopic and immunohistochemical methods. The tumor tissues of chondroblastoma exhibited biphasic pattern i.e., chondroid and cellular area. In the chondroid area, small and round tumor cells contained many filaments in the cytoplasm and small processes in the cell wall. Many glycogen granules were present in the tumor cells in some cases. Intercellular matrix was immunohistochemically positive for S-100 protein and showed fine collagen fibers were very similar to those of articular and epiphysial cartilage. Many portions of mitochondria, cell wall and matrix of chondroblastoma tissue clearly exhibited calcification but were not definitely ossification. In the cellular area, tumor cells were composed of small immature mesenchymal and clear large degenerated tumor cells, histiocytes with lysosomes and osteoclast-like multinuclear giant cells. Immunohistochemical studies in the cellular area revealed that there were many tumor cells positive for lysozyme, alpha 1-antitrypsin and alpha 1 antichymotrypsin. In the transitional zone between chondroid and cellular area, degenerated tumor cells were found. The chondroblastoma was composed of chondroid and histiocytic areas which were very similar to those of chondromyxoid fibroma. The present study appears to demonstrate that chondroblastoma originates from a mixture of chondrocytic and histiocytic tumor cells but not from articular and epiphysial cartilage. PMID- 1512481 TI - [Pull-out strength and bone tissue reaction of plasma-sprayed hydroxyapatite coatings with different thicknesses or substrates]. AB - Synthetic hydroxyapatite has been reported to have good histocompatibility, while metal to have good mechanical properties in vivo. This author coated hydroxyapatite on SUS316L stainless steel and titanium rods, using plasma spraying techniques. Then they were implanted into tubular bones of five dogs. The pull-out strength of hydroxyapatite-coated metals was found to be stronger than that of non-coated metals and increased with passage of the time. After four weeks postoperatively, the coating layer fractured between hydroxyapatite and the metal by the pull-out test. A numerous new bone in contact with hydroxyapatite was observed. Fifty microns is found to be an ideal thickness of the coating layer. The pull-out strength of hydroxyapatite-coated titanium was higher, comparing to that of hydroxyapatite-coated SUS316L stainless steel. These results suggested that perovskite and rutile existed at the interface between hydroxyapatite and titanium after plasma-spraying and made hydroxyapatite to bond tightly to the titanium. Synthetic perovskite showed no pathological reactions to canine bone tissue. PMID- 1512482 TI - [An experimental study on the development of congenital spinal deformity--with special reference to the occurrence and significance of disc anomaly]. AB - This is a histopathological study in mice, using the tail segment of the vertebral column, to investigate the role of intervertebral disc anomalies in the development of congenital spinal deformities. The study was conducted on 222 embryos and 169 postnatal CTT (Crooked-Tailed Toden) mice, a ddY strain with hereditary crooked tails. The earliest detectable anomaly was a serpiginous deformation of the notochord during the notochord stage. Irregular lamination of dense and sparse cell layers of the sclerotome during the membrane stage followed. Then vertebral body and intervertebral disc anomalies clustered around the abnormal notochord, failing to appear separately during the cartilage stage. It was concluded that anomalies of the vertebral body do not appear independently but occur simultaneously with those of the intervertebral disc in the development of congenital spinal deformities. Disc and vertebral body anomalies appear to have equal significance in the pathogenesis of congenital spinal deformities. PMID- 1512483 TI - [An experimental study on compression neuropathy--the effect of neurolysis on the blood-nerve barrier]. AB - The effects of neurolysis on the sciatic nerves of normal controls and in dogs with compression neuropathy were evaluated by macroscopic and electrophysiological studies. The function of the blood-nerve barrier (BNB) was also assessed by Evans blue albumin. Studies on normal sciatic nerves (normal controls): In the epineurectomy group, neither scars nor denervation potentials were recognized. Moreover, the motor nerve conduction velocity (MNCV) and BNB were found to remain normal. In the perineurotomy group, on the other hand, scar formation at the surrounding tissue and denervation potentials were evident. BNB function was impaired and persisted for at least eight weeks. Studies on the compression neuropathy model: MNCV was increased in both the external neurolysis group and the epineurectomy group, and BNB function required six weeks to recover. MNCV was increased in the perineurotomy group, adhesion was severe, and denervation potentials and impairment of the BNB continued. In conclusion, both external neurolysis and epineurectomy restore the function of compressed nerves. There is no significant difference between these methods. Perineurotomy is not considered an appropriate technique for managing compression neuropathy. PMID- 1512484 TI - [An experimental study on the healing of the digital flexor tendon and restoration of gliding function--Part XII--Shortening and changes of physical properties of morphological and functional changes of severed tendons]. AB - The present investigator has sequentially studied gross, histological findings and serial changes of physical properties of severed flexor tendons in young chickens in order to provide information on a primary direct suture of the tendon. In these chickens, the distal portion of the profundus tendon of the third toe was severed then these chickens were divided into two groups. In group 1, the tendon was left in situ (vincula intact). In group 2 (vincula disrupted), the tendon was pulled out proximally to its trifurcation in order to disrupt the vincular system and returned to the original sheath. In group 1, shortening and physical changes were limited to the portion distal to the anchoring of the vinculum and the physical properties were well preserved and remained almost normal. In group 2, the tendon became short and thick. The physical properties were also degenerated markedly. From these results, it was concluded that the vincula greatly effects changes of the physical properties of severed flexor tendons. When vincula was not ruptured, the physiological properties remained almost unchanged resulting in primary suture. When vincula was ruptured and also marked shortening of tendon occurred, primary suture was completed 3 weeks from the restoration of shortened tendon and 2 weeks from degenerating shortened tendon. Combined the above results with such histological changes as thickening of epitenon and tendon and also adhesions, an ideal primary suture appeared to be within one week after severance. PMID- 1512485 TI - [Callus formation and microvascular regeneration during the fracture healing process in the rat femur]. AB - Correlation between the callus formation and its microvascular regeneration during the fracture healing process in the rat femur was examined under SEM and TEM utilizing the plastic injection method. Stabilization of bony fragments was provided by a miniature external fixator. Normal periosteal microvasculature consisted of 2 layers. In the outer layer, arterioles and venules formed the course network. In the inner layer, capillaries were situated in contact with the compact bone, forming polygonal meshes. In the medulla, the central longitudinal artery gave rise to numerous arterioles, which communicated with sinusoidal capillaries. The proliferation of the internal layer of the periosteal capillary network was observed in the periosteal callus. It is revealed that the trabecular structure of the periosteal and medullary calluses depended on their microvascular architecture. The anastomoses of newly-formed capillaries at the fracture site started first from the outer layer of the periosteum extended to the medulla then finally to the inner layer of the periosteum. PMID- 1512487 TI - [Pathomechanics and treatment of carpal instability]. PMID- 1512486 TI - [Experimental study on repair of the defect of the pars interarticularis in rat with bone morphogenetic protein and fibrin glue]. AB - The possibility of repairing the defect of the pars interarticularis (pars defect) with Bone Morphogenetic Protein (BMP) and fibrin glue was studied. The pars defect established in the 5th lumbar vertebra of Wistar rat was treated with surgical implantation of a composite consisting of BMP, fibrin glue and autologous cancellous bone. At 3, 6, 9 and 12 weeks after implantation, the osteoinductive activity in the pars defect was observed histologically and compared with that of other composite implants such as BMP with fibrin glue, autologous cancellous bone alone and autologous cancellous bone with fibrin glue. Although perfect bone fusion was not obtained with any of the composites employed, a significant increase in bone formation was seen in a composite of BMP, fibrin glue and autologous cancellous bone (p less than 0.01) as compared with that seen in the others. Consequently, implantation of BMP and fibrin glue combined with some biomaterials which support osteo-induction of BMP and stabilize the pars defect might be successfully applied to repair the pars defect. PMID- 1512488 TI - [Classification and significance of gastrointestinal polyps]. PMID- 1512489 TI - [Mass screening of stomach polyps by radiography]. PMID- 1512490 TI - [Mass screening of stomach polyps by gastroscopy]. PMID- 1512491 TI - [Mass screening of colonic neoplasms by occult blood test]. PMID- 1512492 TI - [Mass screening of colonic polyps by radiography]. PMID- 1512493 TI - [Mass screening of colonic polyps by colonoscopy]. PMID- 1512494 TI - [Epidemiologic study on cancerous lesions of the gastrointestinal system]. PMID- 1512495 TI - [Natural history and cancerous transformation of gastrointestinal polyps]. PMID- 1512496 TI - [Mass screening of stomach neoplasms by serum pepsinogen analysis]. PMID- 1512497 TI - [Application and limitation of endoscopic polypectomy in stomach polyps]. PMID- 1512498 TI - [Application and limitation of endoscopic polypectomy in colonic polyps]. PMID- 1512499 TI - [Trend and problems of chemotherapy of stomach neoplasms with metastasis]. PMID- 1512500 TI - [Endoscopic polypectomy for therapy of gastrointestinal polyps]. PMID- 1512501 TI - [Gastrointestinal polyps and neoplasms]. PMID- 1512502 TI - [A case of central pontine myelinolysis with myoclonus and frontal sign]. PMID- 1512503 TI - [A case of meningeal myeloma associated with consciousness disorder]. PMID- 1512504 TI - [A case of liver cirrhosis with significant hypoxia--special reference to the respiration physiology on the etiological mechanism]. PMID- 1512505 TI - [Recent topics on nephrotic syndrome]. PMID- 1512506 TI - Why is there sequence similarity between insect yolk proteins and vertebrate lipases? AB - The major proteins stored in the yolk of developing oocytes are thought to provide a nutritional store for utilization during embryogenesis. They seem to fall into two major families of proteins. The first are called vitellogenins and are found in frog, chicken, nematode, fish, and some insects such as the boll weevil. The other group are called yolk proteins and are found in dipteran insects such as fruitfly, housefly, fleshfly, and blue-bottles. Both groups are the major proteins found in the oocyte and are female-specific proteins endocytosed from the serum or hemolymph. The yolk protein group were found to have sequence similarity to the triacylglycerol lipases and lipoprotein lipases of vertebrates, including rat, pig, and human. The yolk proteins do not have lipase activity, but the sequences conserved between yolk proteins and lipases surround the active site where there are interactions with lipids. The likely reason for the presence of this domain in the yolk proteins is to bind a steroid hormone in a storage form conjugated to lipids. This permits the storage of the hormone in an inactive form until the yolk proteins are degraded, when it can be released from its conjugate to induce developmental decisions in embryogenesis. They may also transport lipids into the oocyte for use in embryogenesis. Whilst the vitellogenin family of proteins do not share this homology with the lipases they do have similarity to the human serum protein, apolipoprotein B, which also has a role in binding lipids. These findings are discussed in relation to the evolution and functions of lipases, apolipoproteins, vitellogenins, and yolk proteins. Experiments aimed at isolating genes encoding lipases in insects and at further elucidating the function of the yolk proteins are suggested. PMID- 1512507 TI - Expression of human apolipoprotein E but not that of apolipoprotein A-I by mouse C127 cells is associated with increased secretion of lipids in the form of vesicles and discs. AB - Transfected mouse mammary-derived cells (C127) expressing human apolipoprotein (apo) E (C127E) were used a) to determine whether the lipid-binding character of apoE is sufficient to promote its assembly with lipid to form lipoprotein-like particles when expressed by cells not normally expressing apolipoproteins; b) to characterize the secreted complexes in terms of morphology, size, and composition; and finally c) to determine whether apoE or apoA-I gene expression by these transfected cells has any effect on the levels and the profiles of the synthesized and secreted lipids. The findings of the present study demonstrate that: a) as determined by density gradient ultracentrifugation and gel filtration chromatography, about 20% of the secreted [35S]methionine-labeled apoE expressed by C127E cells is lipid-associated. b) Negative-stain electron microscopic analysis of the lipid-protein complexes recovered in the lipoprotein fractions (d less than 1.21 g/ml) revealed that approximately 13% of the total population of particles were discs (16 +/- 5 nm mean diameter and 4-6 nm thick), resembling nascent high density lipoproteins (HDL). The majority of the particles however (greater than 82%) appeared vesicular with varying diameters (48 +/- 40 nm mean diameter). The discoidal and the vesicular appearance of the particles secreted by C127E cells is consistent with the composition of lipids. These consisted mostly of surface lipids, phospholipids (45 +/- 18%), diacylglycerols (36 +/- 17%), and free cholesterol (17 +/- 7%) (by weight). c) Expression of apoE by C127E cells was associated with an increased release of [35S]methionine-labeled protein and [3H]glycerol-labeled lipid (3- to 5- and 4- to 8-fold, respectively) compared to nontransfected C127 cells. Expression of mutant apoE or normal apoA I, however, was not associated with increased release of the major lipid classes compared to the parent C127 cells, strongly suggesting that this character of C127E cells is specific to apoE expression. The release of lipids by C127E cells could be reduced considerably by the addition of the metabolic inhibitors, colchicine or cycloheximide (10 and 1 microM, respectively), suggesting that lipid release by C127E cells is an active process requiring both protein synthesis and functional secretory mechanisms. Taken together the findings suggest that apoE expression by C127 cells promotes the formation of nascent discoidal lipoprotein-like particles and enhances the release of vesicular lipids, possibly by promoting shedding of cell plasma membrane fragments. PMID- 1512508 TI - Sialic acid content of human low density lipoproteins affects their interaction with cell receptors and intracellular lipid accumulation. AB - Low density lipoproteins (LDL) isolated from the plasma of patients with angiographically demonstrable coronary heart disease (CHD) induced accumulation of triglycerides, free cholesterol, and cholesteryl esters in cultured macrophages, smooth muscle cells, and endothelial cells derived from uninvolved intima of human aorta, but not in skin fibroblasts or hepatoma cells. The sialic acid content of LDL from CHD patients was 40-75% lower than that from healthy donors. There was a negative correlation between LDL sialic acid content and the LDL-induced accumulation of total intracellular cholesterol. Neuraminidase treatment of LDL from normal healthy donors produced sialic acid-depleted LDL (Ds LDL) which was able to stimulate intracellular lipid accumulation. Neuraminidase treatment of LDL from CHD patients further increased its capacity to induce intracellular lipid accumulation. Sialic acid-poor LDL isolated by affinity chromatography of LDL from CHD patients induced a 2- to 4-fold increase of free and esterified cholesterol in human intimal smooth muscle cells. Binding, uptake, and degradation of 125I-labeled Ds-LDL by macrophages and endothelial cells were 1.5- to 2-fold higher than for native LDL. Binding and uptake of Ds-LDL was inhibited 64-93% by the addition of 20-fold excess acetylated LDL (Ac-LDL); in the inverse experiment, the level of inhibition was 35-54%. These data indicate that a sialic acid-poor form of LDL isolated from CHD patients can interact with both native and scavenger LDL receptors. A sialic acid-poor form of LDL may be a naturally occurring ligand that interacts with the scavenger receptor(s) on macrophages and endothelial cells. PMID- 1512509 TI - Defective catabolism of oxidized LDL by J774 murine macrophages. AB - In J774 murine macrophages, chemically oxidized LDL (OxLDL) and biologically oxidized LDL (BioOxLDL) have similar metabolic fates, characterized by a relatively poor degradation when compared with acetylated LDL (AcLDL), and a modest ability to activate acyl-CoA:cholesterol acyltransferase (ACAT) (850 and 754 pmol [14C]oleate/mg cell protein in OxLDL- and BioOxLDL-incubated cells, versus 425 and 7070 pmol [14C]cholesteryl oleate/mg cell protein in control and AcLDL-incubated cells) with a massive increase of cellular free cholesterol. Therefore, OxLDL were used to investigate the cellular processing of oxidatively modified LDL. Binding and fluorescence microscopy studies demonstrated that OxLDL are effectively bound and internalized by macrophages and accumulate in organelles with density properties similar to those of endo/lysosomes. Although the overall metabolism of OxLDL is modestly affected by 100 microM chloroquine, owing to the poor cellular degradation of the substrate, the drug can further depress OxLDL degradation, indicating that this process takes place in an acidic compartment. Failure to detect products of extensive degradation of OxLDL in the medium is due to their relative resistance to enzymatic hydrolysis, as demonstrated also by in vitro experiments with partially purified lysosomal enzymes, rather than to the intracellular accumulation of degradation products (degraded intracellular protein is, at most, 8.5% of total). This sluggish degradation process is not due to a cytotoxic effect since OxLDL do not affect the intracellular processing of other ligands like AcLDL or IgG. The accumulation of OxLDL-derived products within macrophages may elicit cellular responses, the relevance of which in the atherosclerotic process remains to be addressed. PMID- 1512510 TI - Evolutionary distinct mechanisms regulate apolipoprotein A-I gene expression: differences between avian and mammalian apoA-I gene transcription control regions. AB - In mammals, the apolipoprotein (apo) A-I gene is expressed predominantly in liver and intestine, while in avian species it is expressed in all tissues. Although liver and intestine are the major sites of chicken apoA-I mRNA synthesis, there are appreciable amounts of apoA-I mRNA in kidney, ovary/testes, brain, lung, skeletal, and heart muscle. In this study, the nucleotide sequences of the chicken apoA-I gene and its 5' flanking region, as well as the sequences involved in the expression of this gene, have been determined. The gene spans 1.5 kilobases and contains 4 exons and 3 introns, closely resembling the mammalian apoA-I gene. To determine the sequences involved in the expression of the chicken apoA-I gene, plasmid constructs containing serial deletions of the 5' flanking region of the chicken apoA-I gene fused to the bacterial chloramphenicol acetyltransferase (CAT) gene were transfected in human hepatoma (HepG2), colon carcinoma (Caco2), epithelial (Hela), mouse embryonal fibroblast (NIH3T3) cells, and quail myoblasts (QMLA29). The shortest deletion construct, containing 60 bp of the 5' upstream region, was sufficient for maximal transcriptional activity in all cell lines tested. This region contains a short sequence (nucleotides -60 to 54) that is highly conserved in birds and mammals, and an Sp1 binding site. Although the sequence between nucleotides -232 and -101 of the 5' region of the chicken apoA-I gene is partially homologous to the hepatic cell-specific enhancer of the mammalian apoA-I gene (located between nucleotides -222 and -110 upstream of the human apoA-I gene transcription start site), this chicken sequence is transcriptionally inactive in HepG2 cells. These results suggest that differences in the cis-acting regulatory elements of the apoA-I gene play a fundamental role in determining the differences in the tissue-specific expression of this gene in avian and mammalian species. PMID- 1512511 TI - Inhibition of fatty acid synthesis decreases very low density lipoprotein secretion in the hamster. AB - The hamster was developed as a model to study very low density lipoprotein (VLDL) metabolism, since, as is the case in humans, the hamster liver was found to synthesize apoB-100 and not apoB-48. The effect of inhibiting fatty acid synthesis on the hepatic secretion of VLDL triglyceride (TG) and apolipoprotein (apo) B-100 in this model was then investigated. In an in vivo study, hamsters were fed a chow diet containing 0.15% TOFA (5-tetradecyloxy-2-furancarboxylic acid), an inhibitor of acetyl-CoA carboxylase. After 6 days of treatment, plasma triglyceride and cholesterol levels were decreased by 30.2% and 11.6%, respectively. When the secretion of VLDL-TG by the liver was measured in vivo after injection of Triton WR 1339, TOFA treatment was found to decrease VLDL-TG secretion by 40%. In subsequent in vitro studies utilizing cultured primary hamster hepatocytes, incubation with 20 microM TOFA for 4 h resulted in 98% and 76% inhibition in fatty acid and triglyceride synthesis, respectively; VLDL-TG secretion was decreased by 90%. When hepatocytes were pulsed with [3H]leucine, incubation with TOFA resulted in a 50% decrease in the incorporation of radiolabel into secreted VLDL apoB-100. The results of this study indicate that inhibition of intracellular triglyceride synthesis decreases the secretion of VLDL-TG and apoB-100, and does not result in the secretion of a dense, triglyceride-depleted lipoprotein. PMID- 1512513 TI - Effect of dietary supplementation with alpha-tocopherol on the oxidative modification of low density lipoprotein. AB - Much data has accumulated supporting a proatherogenic role for oxidized low density lipoprotein (Ox-LDL). Micronutrient antioxidants such as alpha tocopherol, the principal lipid-soluble antioxidant, assume potential significance because levels can be manipulated by dietary measures without resulting in side effects. Co-incubation of LDL in vitro with alpha-tocopherol inhibits its oxidative modification. Hence the effect of dietary supplementation with alpha-tocopherol on the time course of copper-catalyzed oxidation of LDL was tested in a randomized placebo-controlled single-blind study. Two groups of 12 male subjects were given either placebo or alpha-tocopherol (800 IU/day) for a period of 12 weeks. Alpha-tocopherol therapy did not result in any side effects or exert an adverse effect on the plasma lipid and lipoprotein profile. While the lipid standardized alpha-tocopherol levels were similar at baseline, the supplemented group had 3.3-fold and 4.4-fold higher levels compared to placebo at 6 and 12 weeks, respectively. In the 15 subjects in whom both plasma and LDL alpha-tocopherol levels were quantitated, there was a significant correlation (r = 0.79, P less than 0.0001). At baseline there were no significant differences in the time course curves of thiobarbituric acid-reacting substances (TBARS) activity or conjugated diene formation between the alpha-tocopherol and placebo groups. However, at both 6 and 12 weeks the mean levels of TBARS activity and conjugated diene formation were lower in the alpha-tocopherol group; the most significant differences were manifest at the 3-h time point. Also at both 6 and 12 weeks the mean rate of oxidation was lower in the alpha-tocopherol group.2+_ PMID- 1512512 TI - Trp64----nonsense mutation in the lipoprotein lipase gene. AB - A lipoprotein lipase (LpL) gene defect has been identified, a G----A transition at nucleotide position 446 of exon 3, resulting in a premature termination codon (Trp----stop) at amino acid residue 64. This defect was identified in a Type I hyperlipoproteinemic subject with an amino acid residue 194 defect in the other allele. Plasma lipoprotein values as well as LpL mass and activity in postheparin plasma were determined in the subjects with the residue 64 defect and in other LpL-deficient heterozygotes. LpL mass levels in both the Type I and the other subject with a 64 LpL defect were markedly reduced. This may be explained by rapid degradation of LpL protein or decreased secretion from the 64 defective allele. Alternatively, the marked reduction or absence of mass associated with the 64 defect may be due to synthesis of a severely truncated protein which escapes immunologic detection. PMID- 1512514 TI - Measurement of human apolipoprotein B-48 and B-100 kinetics in triglyceride-rich lipoproteins using [5,5,5-2H3]leucine. AB - A primed-constant infusion of deuterated leucine was used in humans to determine the maximal level of enrichment at plateau of apolipoprotein (apo)B-48 and apoB 100 which are synthesized in the intestine and liver, respectively, and to compare the kinetics of these two proteins under identical conditions. Eight normal subjects (four post-menopausal females and four males) over the age of 40 were studied in the constantly fed state over a 20-h period by providing small hourly feedings of identical composition. [5,5,5-2H3]Leucine (10 mumol/kg body weight followed by 10 mumol/kg body weight per hour) was infused over 15 h intravenously. The enrichment of deuterated leucine in apoB-48 and apoB-100 triglyceride-rich lipoproteins isolated by ultracentrifugation (d less than 1.006 g/ml) was determined during the entire infusion period. The plateau level of enrichment in triglyceride-rich lipoprotein apoB-48 was 3.96 +/- 1.41 tracer/tracee ratio (%) which was 39.7% of the plasma leucine enrichment level. The plateau level of enrichment in triglyceride-rich lipoprotein apoB-100 was 7.23 +/- 1.17 tracer/tracee ratio (%) which was 72.5% of the plasma leucine enrichment level. Mean fractional secretion rates of triglyceride-rich lipoprotein apoB-48 and apoB-100 were 4.39 +/- 2.00 and 5.39 +/- 1.98 pools per day, respectively, with estimated residence times of 5.47 and 4.45 hours, respectively. The data indicate that in the fed state there is about a twofold difference in the plateau enrichment of an intestinally derived protein, as compared to one of hepatic origin, most likely attributable to differences in the enrichment of the intracellular leucine in the two organs.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1512515 TI - Characterization of chylomicron remnant clearance by retinyl palmitate label in normal humans. AB - To characterize chylomicron remnant clearance by the liver, plasma elimination of retinyl palmitate-labeled chylomicron remnants was studied in 18 healthy subjects, ages 21-42 years. Autologous plasma containing retinyl palmitate labeled chylomicrons and their remnants was injected intravenously, and retinyl palmitate disappearance was measured in serial plasma samples in all subjects and in lipoprotein fractions in 11 subjects. The injected doses (n = 18) ranged from 0.34 to 7.11 mumol retinyl palmitate in d less than or equal to 1.006 g/ml particles with an average molar ratio of 330/1 of retinyl palmitate/apoB-48 (n = 8). The label distributed in the intravascular space and exhibited apparent first order elimination, monoexponential in 6 and biexponential in 12 subjects. The first rapid component k1 (t1/2 18.8 +/- 11.4 min, n = 18) was shown to represent retinyl palmitate in particles of d less than or equal to 1.006 g/ml, i.e., chylomicron remnants, and the second slow component k2 (t1/2 123 +/- 62 min, n = 12) small amounts of retinyl palmitate (11 +/- 7%) injected in d greater than 1.006 g/ml particles (therefore excluded from analysis). Assuming a single compartment model, initial rates of elimination (= dose x k1) of labeled chylomicron remnants obeyed (P = 0.06) Michaelis-Menten saturation kinetics: Km was 921 +/- 305 nmol retinyl palmitate label and Vmax 124 +/- 14 nmol/min corresponding to 0.88 nM apoB-48 for Km and 0.25 x 10(-3) nmol apoB-48.min-1.g-1 liver for Vmax. Their elimination was limited neither by the injected triglyceride dose nor theoretically by the liver blood flow. After the intake of 70 g of fat (cream) containing retinyl palmitate, the plasma retinyl palmitate concentration exceeded the estimated saturation concentration for 7 h. In conclusion, physiological chylomicron remnant catabolism by the liver appears to be saturable by ordinary lipid intake in healthy humans. PMID- 1512516 TI - Combination of an enzymatic method and HPLC for the quantitation of cholesterol in cultured cells. AB - The study of the cellular events that lead to the foam cell formation requires the development of fast, accurate, and sensitive methods to quantify cholesterol in cultured cells. Here we describe a procedure that allows the rapid determination of free and total cholesterol in a reduced number of cells, which makes it very suitable for cholesterol determination in cell cultures. The method consists of the enzymatic conversion of cholesterol to cholest-4-ene-3-one by cholesterol oxidase followed by the analysis of the sample by high performance liquid chromatography (HPLC) to detect this oxidized product. Due to the relatively high wavelength at which cholest-4-ene-3-one has its maximum absorption (240 nm), other cellular components do not interfere with the chromatographic procedure and prior lipid extraction is not required. Moreover, the duration of each chromatogram is about 3 min, contributing to the celerity of the method. All the cholesteryl esters used (oleate, palmitate, stearate and linoleate) were quantitatively hydrolyzed by incubation with cholesterol esterase; this was observed to occur with both pure standards and in cell homogenates. Sensitivity is enough to allow the determination of free and total cholesterol in less than 5 x 10(3) cells. We have applied this method to human monocyte-derived macrophages and the values obtained for free and total cholesterol are in close agreement with published data. PMID- 1512517 TI - Aspen Bile Acid/Cholesterol Conference 1991. Report of a conference. PMID- 1512518 TI - Theophylline transfer across human placental cotyledon during in vitro dual perfusion. AB - In vitro placental perfusion is widely used to investigate the placental transfer of endogenous compounds and, to a lesser extent, that of drugs. The aim of this study was to assess the suitability and reliability of such in vitro systems for application on drug placental transfer studies. We investigated the time course of theophylline (TH) transfer, a drug frequently used in the perinatal period. Eight experiments were performed with maternal and fetal circuits maintained in an open system, perfusing placentas for 160 min with Earle's enriched bicarbonate buffer containing two test substances, antipyrine (AP), (80 mg/L) and creatinine (CR), (150 mg/L), and the tool drug TH (15 mg/L). All substances equilibrated in our system with times proportional to the chemical-physical characteristics of each compound, being the time required to reach the steady state 5 to 12 min for AP, 12 to 31 min for CR and 10 to 35 min for TH. AP and CR clearances were 2.94 +/- 0.33 and 0.83 +/- 0.26 mL/min, respectively. The transfer profile of TH was similar to that of AP and its clearance was 2.39 +/- 0.37 mL/min, with a clearance index of 0.80 +/- 0.11. Transfer percentages of TH are in agreement with in vivo values for both humans and animals, and with results obtained during in situ placental perfusion in the rabbit. Physiological conditions and biochemical properties of the tissue were well maintained throughout perfusion. Glucose consumption and lactate release were, respectively, 0.65 +/- 0.16 and 0.73 +/- 0.11 mumoles/min/g. Oxygen consumption was 5.29 +/- 1.32 mL/min/kg and oxygen transfer from the maternal to fetal circuit was 0.99 +/- 0.43 mL/min/kg. The findings support the reliability of this technique to study transplacental passage of drugs, and the relevance of such a model to obtain information concerning potential therapeutic or toxicologic effects of drugs during the last trimester of pregnancy. PMID- 1512519 TI - Multiple organ failure in patients with fulminant hepatitis and in post-operative patients with liver cirrhosis. AB - Multiple organ failure (MOF) appeared during the course of nine cases with fulminant hepatitis, and it was compared with that of seven cirrhotic patients with post-operative hepatic failure. The number of organs failed was 4.9 and 3.6 on average in fulminant hepatitis and post-operative cirrhosis, respectively. All the patients died in less than nine days following the occurrence of MOF. Gastrointestinal bleeding was more frequently observed in fulminant hepatitis cases than in cirrhotic patients. In post-operative cirrhotics, hepatic failure occurred later and the elevation of serum total bilirubin was mild and slow. Renal failure and/or gastrointestinal bleeding was observed prior to death in fulminant hepatitis cases, and cardiac failure and hepatic failure in post operative cirrhotics. These organ failures resulted in death, although extensive and multimodal treatments were carried out in both groups of patients. PMID- 1512520 TI - Iak antigen and interleukin-1 secretion by lymphocytes and monocytes of mice fed a lipid-rich diet. AB - Female mice were maintained on a lipid-rich diet. After 33 days, the mice showed a decrease in the cell population bearing MHC class II molecules, and in the production of interleukin-1 (IL-1). After 60 days, we reported a further decrease of the cell population with MHC class II molecules and the secretion IL-1. PMID- 1512521 TI - Effect of hypoimmunoglobulinemia on laboratory evaluation of multiple sclerosis. AB - A female patient with Crohn's disease was assessed by laboratory evaluation for multiple sclerosis. Because of her hypoproteinemia, she was given an albumin infusion, which caused immunoglobulin concentrations to fall below the normal limit. Based on a cerebrospinal fluid (CSF) sample drawn after infusion, she was found to have an abnormally high IgG index and a high intrathecal IgG synthesis rate. However, clinical correlations ruled out demyelinating disease. Various equations used for the calculation were examined and found to yield false positive results with values of serum IgG below the reference range. Only the Ohman formula provided the correct prediction in this patient. Although hypo- or hyper-albuminemia have little effect on these equations, they may escalate the impact of hypoimmunoglobulinemia. Thus, interpretation of laboratory data under these conditions must be exercised with care. PMID- 1512522 TI - Hematopoietic progenitor cells in a patient with myeloid metaplasia without myelofibrosis. AB - A rare case of myeloid metaplasia without myelofibrosis is presented. Findings that the increase in blood megakaryocyte progenitor cells was not as prominent as the increase in granulocyte-monocyte and erythroid progenitor cells, and that the increase in bone marrow megakaryocytes was only slight might explain the absence of bone marrow fibrosis in this case. However, it is not clear whether the disease is a subtype or merely an early stage of myelofibrosis with myeloid metaplasia. PMID- 1512523 TI - Treatment of severe immune deficiency with radio-detoxified endotoxin. PMID- 1512524 TI - Indobufen versus dipyridamole plus aspirin in the treatment of patients with peripheral atherosclerotic disease. AB - Twenty-seven patients with peripheral atherosclerotic disease were randomized into two therapy regimens consisting of indobufen (Indo) (400 mg/day) and dipyridamole (Dip) (225 mg/day) plus acetylsalicylic acid (ASA) (1 g/day), respectively. Maximal walking distance (MWD) and ankle-arm systolic pressure ratios were measured before and after three and six months of therapy; bleeding time, beta-thromboglobulin (beta-TG), platelet factor 4 (PF4) and serum thromboxane B2 (TXB2) were also assessed. The two treatment groups showed a significant and progressive increase in pain-free walking distance at both three and six months of therapy, but patients taking indobufen showed a greater improvement. On the contrary, the pressure doppler ratio at rest was statistically improved only in the ASA plus Dip group. Basal beta-TG and PF4 levels were normal and no changes occurred during the study in either group, while in all patients bleeding times showed a significant increase above basal values and serum TBX2 decreased. PMID- 1512525 TI - Fibrinopeptide-A as thrombotic risk marker in diabetic and atherosclerotic coronary vasculopathy. AB - Fibrinopeptide A was determined in 75 middle aged male patients, five control subjects and a control group of young medical students, divided into nine subsets. The FPA levels were significantly elevated in the patient group, particularly among the diabetics, when compared with the medical students and also age matched controls. Diabetic patients who smoked and had vascular pathology had high FPA levels even after they stopped smoking. PMID- 1512526 TI - Of our country. PMID- 1512527 TI - Juggling fiduciary responsibility--how to avoid dropping the ball. PMID- 1512528 TI - Managing your office manager. PMID- 1512529 TI - Needed: improvement in the relationship between medical staffs and hospitals. PMID- 1512530 TI - Helpful hints in structuring physician employment agreements. PMID- 1512531 TI - Investigating SIDS and other infant deaths. PMID- 1512532 TI - Current perspectives on papillary carcinoma of the thyroid gland. AB - Papillary carcinoma is the most common of the carcinomas of the thyroid gland, but it is also the one with the best prognosis. At the present, diagnosis is best done by fine needle aspiration, and treatment by surgical resection. With recent advances in molecular and cellular biology, diagnosis and therapy in the future may depend on micromolecular technologies. The prognosis is promising for increased success in the treatment of papillary carcinoma. PMID- 1512533 TI - Transfer of zymosan (yeast cell walls) to the parasitophorous vacuoles of macrophages infected with Leishmania amazonensis. AB - Leishmania are flagellated protozoan parasites which, in their amastigote stages, survive and multiply within phagolysosome-like parasitophorous vacuoles (PV) of mammalian macrophages (MO). This study develops an earlier ultrastructural, incidental observation that zymosan particles (Z) were transferred to the PV of macrophages infected with Leishmania amazonensis. In the present report, a pulse chase light microscopic assay was used to delineate several features of the Z transfer. The assay reflects both the movement of internalized particles to a position adjoining a PV, and their delivery to the vacuoles. Transfer was selective, in the sense that Z, beta-glucan or heat-killed yeast particles were transferred, whereas latex beads, aldehyde-fixed, or immunoglobulin G-coated erythrocytes were not. This selectivity may be related to the high density of carbohydrate ligands displayed on the surface of yeast-derived particles, to ligand resistance to lysosomal degradation or to signals encoded in the cytosolic tails of the receptors involved in particle recognition. A few Z particles could be found within PV after 1 h of incubation with infected MO, but chase periods of several hours at 34 degrees C were required for particle transfer to the PV in a substantial proportion of the MO. Ammonium chloride, chloroquine, or monensin, compounds which increase the pH in acidified compartments, substantially enhanced the transfer of Z particles. Finally, transfer was inhibited by cytochalasin D, but was unaffected by the antitubulin nocodazole. Although it is not yet known if particle transfer occurs by fusion of donor vesicles with PV or by interiorization of the former into the latter, the model described should be useful in the study of the interactions between large phagocytic vesicles and the modulation of those interactions by cellular, parasitic, and environmental signals. PMID- 1512534 TI - Sialoadhesin on macrophages: its identification as a lymphocyte adhesion molecule. AB - In this study we present evidence that the mouse and rat sialoadhesin (originally named sheep erythrocyte receptor) on macrophages can function as a lymphocyte adhesion molecule. Lymphocytes were shown to bind to the splenic marginal zone, and lymph node subcapsular sinus and medulla in a frozen section assay. Selective depletion experiments showed that binding was mediated by macrophages. Adhesion was blocked by preincubation of the sections with monoclonal antibodies against mouse or rat sialoadhesin. Binding was temperature dependent, divalent cation independent, and involved sialic acid residues on the lymphocyte, as it could be inhibited by prior neuraminidase treatment or addition of the ganglioside GD1a. Binding to sialoadhesin was confirmed using the purified receptor and was observed among T cells, T blasts, B cells, and B blasts. Isolated macrophages or dendritic cells showed little binding. Sialoadhesin provides the first example of a macrophage-restricted lymphocyte adhesion molecule. PMID- 1512535 TI - HLA-DR associates with specific stress proteins and is retained in the endoplasmic reticulum in invariant chain negative cells. AB - The major histocompatibility complex class II molecules are composed of two polymorphic chains which, in cells normally expressing them, transiently associate with a third, nonpolymorphic molecule, the invariant chain (Ii). To determine differences in the biology of class II molecules synthesized in the presence or absence of Ii, a comparative study was performed of BALB/c 3T3 cells that had been transfected with human class II HLA-DR molecules with or without cotransfection with human Ii. It was observed that in the absence of Ii, at least three high molecular weight proteins coimmunoprecipitate with HLA-DR molecules. These proteins did not coimmunoprecipitate with HLA-DR from cells cotransfected with Ii, nor did they coimmunoprecipitate with class I molecules from any of the transfectants. NH2-terminal sequence and/or Western blot analysis revealed the identity of two of the proteins as the endoplasmic reticulum (ER) resident stress proteins GRP94 and ERp72. Neither of these proteins was found to have an increased level of synthesis in the Ii- versus the Ii+ transfectants, indicating that their synthesis was not induced over constitutive levels. Fluorescence microscopy revealed that in the Ii- transfectants, the majority of the HLA-DR molecules were present in the ER, whereas in the Ii+ transfectants, the HLA-DR molecules were found in vesicular structures. We hypothesize that in the absence of Ii, ER resident stress proteins bind to class II molecules and retain them in the ER. This process, in turn, could prevent class II molecules from exiting the ER with endogenous peptides bound in their peptide binding cleft, and therefore could minimize autoimmune responses to endogenously processed self-peptides. PMID- 1512536 TI - In situ studies of the primary immune response to (4-hydroxy-3 nitrophenyl)acetyl. II. A common clonal origin for periarteriolar lymphoid sheath associated foci and germinal centers. AB - In the genetically restricted response that follows immunization with (4-hydroxy 3-nitrophenyl)acetyl coupled to protein carriers, two distinct populations of B cells are observed in the spleens of C57BL/6 mice. By 48 h postimmunization, foci of antigen-binding B cells appear along the periphery of the periarteriolar lymphoid sheaths. These foci expand to contain large numbers of antibody-forming cells that neither bind the lectin, peanut agglutinin, nor mutate the rearranged immunoglobulin variable region loci. Germinal centers containing peanut agglutinin-positive B cells can be observed by 96-120 h after immunization. Although specific for the immunizing hapten, these B cells do not produce substantial amounts of antibody, but are the population that undergoes somatic hypermutation and affinity-driven selection. Both focus and germinal center populations are pauciclonal, founded, on average, by three or fewer B lymphocytes. Despite the highly specialized roles of the focus (early antibody production) and germinal center (higher affinity memory cells) B cell populations, analysis of VH to D to JH joins in neighboring foci and germinal centers demonstrate that these B cell populations have a common clonal origin. PMID- 1512537 TI - Distinctive selection mechanisms govern the T cell receptor repertoire of peripheral CD4-CD8- alpha/beta T cells. AB - The T cell receptor (TCR) repertoire of CD4+ and CD8+ alpha/beta T cells is heavily influenced by positive and negative selection events that occur during T cell development in the thymus. The coreceptors CD4 and CD8 appear to be essential for this selection to occur. To gain insight into whether T cells that express TCR alpha/beta but lack either coreceptor (CD4- CD8- TCR alpha/beta or alpha/beta double-negative [DN] cells) are also subject to positive and negative selection, and whether selection can occur in the absence of coreceptors, we have performed an extensive immunogenetic analysis of the TCR V beta repertoire of alpha/beta DN cells in lymph nodes of normal mice. Our results show that alpha/beta DN cells appear to be unaffected by clonal deletion of V beta 5 and V beta 11 in I-E-expressing mice, and do not undergo deletion of V beta 6- and V beta 8.1-expressing T cells in Mls-1a-positive mice. They are also unaffected by positive selection of V beta 17a+ T cells in the context of I-Aq. The results suggest that most selection events require the participation of CD4 and CD8, while alpha/beta DN cells are unselected. This argues that most alpha/beta DN cells probably have never expressed CD4 or CD8. However, a unique form of repertoire selection occurs: enrichment of V beta 17a+ alpha/beta DN cells in I E+ mice. This could be an instance of coreceptor-independent selection. PMID- 1512538 TI - Viral neuroinvasion and encephalitis induced by lipopolysaccharide and its mediators. AB - The present study was designed to test the effect of bacterial endotoxin on penetration of viruses into the central nervous system (CNS). As a model we used two neurovirulent viruses that lack neuroinvasive capacity: West Nile virus-25 (WN-25) and neuroadapted Sindbis virus (SVN). Administration of lipopolysaccharide (LPS, 100 micrograms/mouse) to CD-1 mice, followed by WN-25 inoculation resulted in 83% encephalitis and death, compared with less than 5% in controls. The results in SVN-inoculated CD-1 mice were quite similar. LPS-treated mice suffered 62% mortality compared with 6% in the nontreated group. No changes in viral neuroinvasiveness were demonstrated in viruses isolated from brains of encephalitic mice, suggesting that neuroinvasion is not due to a selection process for an invasive variant, but to direct penetration of the viruses through the blood-brain barrier (BBB). LPS did not induce WN-25 encephalitis in LPS insensitive C3H/HeJ mice, compared with 100% neuroinvasion in C3H/HeB mice. Induction of neuroinvasion could be transferred to C3H/HeJ mice by transfusion with serum obtained from LPS-treated, LPS-responsive mice. Passive immunization of CD-1 mice with anti-mTNF antibodies before LPS administration did not prevent LPS-induced WN-25 encephalitis. Furthermore, neutralization of tumor necrosis factor activity in the serum of LPS-treated mice did not abolish its activity, and transfusion-associated encephalitis was observed after the administration of the neutralized serum with WN-25. We suggest that LPS can contribute to virus penetration from the blood into the CNS, a process which turns a mild viral infection into a severe lethal encephalitis. This effect is mediated by soluble factors, and is probably achieved by injury to cerebral microvascular endothelium and modulation of BBB permeability. PMID- 1512539 TI - Interferon gamma induces the expression of human immunodeficiency virus in persistently infected promonocytic cells (U1) and redirects the production of virions to intracytoplasmic vacuoles in phorbol myristate acetate-differentiated U1 cells. AB - Interferon gamma (IFN-gamma), a lymphokine that exerts multiple immunoregulatory effects, has been found to be elevated in the plasma, cerebrospinal fluid, and lymph nodes of human immunodeficiency virus (HIV)-infected individuals and has shown variable effects on HIV replication in acutely infected cells. In the present study, we have demonstrated that IFN-gamma is a potent modulator of HIV expression in persistently infected U1 promonocytic cells in which virus production is characterized by a constitutive state of relative latency. Direct stimulation of U1 cells with IFN-gamma (10-1,000 U/ml) activated HIV expression, as measured by reverse transcriptase (RT) activity in the culture supernatant and increased levels of cell-associated viral protein and mRNAs. These effects on virus expression were not accounted for by the induction of endogenous TNF-alpha secretion, as previously described in U1 cells stimulated with phorbol myristate acetate (PMA). At the ultrastructural level, the stimulatory activity of IFN gamma was correlated with HIV particle production in intracytoplasmic vacuoles along with the differentiation of U1 into macrophage-like cells. Furthermore, costimulation of U1 cells with IFN-gamma and PMA significantly increased the accumulation of vacuole-associated HIV concomitant with decreasing membrane associated particles and RT activity production, as compared with cells stimulated with PMA alone. No evidence of spontaneous secretion of intracellular vacuole-associated virus was obtained by kinetic analysis of the RT activity released in the supernatants throughout the culture period unless cells were deliberately disrupted. These findings suggest that vacuole-associated virions likely represent a relatively stable intracellular reservoir of HIV, as previously described in primary macrophages infected in vitro or in infected macrophages in the brains of patients with acquired immune deficiency syndrome. The reduced levels of RT activity observed in the culture supernatants of U1 cells stimulated with PMA in the presence of IFN-gamma were not indicative of a suppressive effect of IFN-gamma on PMA-induced expression of HIV proteins and mRNAs, either directly or mediated by the release of IFN-alpha/beta. This study suggests that IFN-gamma may play an important role as an inducer of HIV expression in infected mononuclear phagocytes. PMID- 1512540 TI - Both IgM and IgG anti-DNA antibodies are the products of clonally selective B cell stimulation in (NZB x NZW)F1 mice. AB - Disease activity in systemic lupus erythematosus is closely associated with the appearance of immunoglobulin (Ig)G antibody to native DNA in both humans and mice. Like normal antibody responses, the anti-DNA autoantibody first appears as IgM and then switches to IgG. Structural studies of IgG anti-DNA suggest that these antibodies are the products of clonally selected, specifically stimulated B cells. The origins of the IgM anti-DNA have been less clear. To determine whether the earlier appearing IgM anti-DNA antibody in autoimmune mice also derives from clonally selected, specifically stimulated B cells or B cells activated by nonselective, polyclonal stimuli, we have analyzed the molecular and serological characteristics of a large number of monoclonal IgM anti-DNA antibodies from autoimmune (NZB x NZW)F1 mice. We have also analyzed IgM and IgG anti-DNA hybridomas obtained from the same individual mice to determine how the later appearing IgG autoantibody may be related to the earlier-appearing IgM autoantibody within an individual mouse. The results demonstrate that: (a) IgM anti-DNA, like IgG, has the characteristics of a specifically stimulated antibody; (b) IgM and IgG anti-DNA antibodies have similar variable region structures and within individual mice may be produced by B cells derived from the same clonal precursors; (c) recurrent germline and somatically derived VH and VL structures may influence the specificity of anti-DNA monoclonal antibody for denatured vs. native DNA; and (d) the results provide a structural explanation for the selective development of IgG antibody to native DNA as autoimmunity to DNA progresses in (NZB x NZW)F1 mice. PMID- 1512541 TI - Macrophage inflammatory protein-1 alpha activates basophils and mast cells. AB - Macrophage inflammatory protein-1 (MIP) is a recently cloned cytokine that causes neutrophilic infiltration and induces an inflammatory response. We studied the effect of MIP-1 alpha on histamine secretion from basophils and mast cells. Leukocytes from allergic and normal subjects were studied. MIP-1 alpha caused dose-dependent release of histamine from basophils of 14 of 20 allergic donors at concentrations of 10(-9)-10(-7) M, and the mean release was 13.50 +/- 2.9% at the highest concentration. In the same experiments, the mean histamine release by anti-immunoglobulin E and monocyte chemotactic and activating factor (MCAF) (10( 7) M) was 32 +/- 7% and 31 +/- 3%, respectively. The cells from only 2 of 10 normal subjects released histamine in response to MIP-1 alpha. Histamine release by MIP-1 alpha was rapid, and almost complete within the first 3 min. MIP-1 alpha induced degranulation was a calcium-dependent noncytotoxic process. MIP-1 alpha showed chemotactic activity for purified basophils that was comparable to MCAF. Both MIP-1 alpha and MCAF at 10(-7) M concentration elicited a chemotactic response that was 40% of the maximal response to C5a (1 microgram/ml). Murine MIP 1 alpha induced histamine release from mouse peritoneal mast cells in a dose dependent manner. Thus, we have established that MIP-1 alpha is a novel activator of basophils and mast cells. PMID- 1512542 TI - NF-kappa B-like factors mediate interleukin 1 induction of c-myc gene transcription in fibroblasts. AB - Interleukin 1 (IL-1) is a pluripotent cytokine involved in mediating a variety of physiological processes, including induction of cell proliferation upon wound healing. Treatment of quiescent FS-4 human dermal fibroblast cells with IL-1 activates c-myc gene transcription, and nuclear localization of NF-kappa B. Previously, we have noted that the murine c-myc gene contains two functional NF kappa B sites located at -1101 to -1081 bp (upstream regulatory element [URE]) and +440 to +459 bp (internal regulatory element [IRE]) relative to the P1 promoter. Here we have demonstrated that IL-1 treatment induced binding of NF kappa B-like proteins (p50/p65) to these c-myc elements. Heterologous promoter CAT constructs driven by multiple copies of either the URE or IRE were IL-1 inducible when transfected into FS-4 cells. In contrast, constructs harboring elements with two G to C residue conversions, such that they were no longer able to bind NF-kappa B, were not responsive to IL-1. Mutation of these two base pairs at both NF-kappa B sites within a c-myc promoter/exon I-CAT construct, resulted in loss of inducibility with IL-1 upon transfection into quiescent FS-4 cells. Thus, IL-1 significantly induces c-myc expression through positive regulation by NF-kappa B, suggesting a role for this family of factors in activation of proliferation associated with wound healing. PMID- 1512543 TI - Long-lived complexes between peptide and class II major histocompatibility complex are formed at low pH with no requirement for pH neutralization. AB - The binding of peptide antigens to class II histocompatibility glycoproteins can be markedly enhanced at pH values approximating those found in acidic endosomal compartments in antigen-presenting cells (APC). It has been proposed by others that low pH may increase the conformational flexibility of class II, facilitating both the association and dissociation of peptides. Neutralization of pH, as class II is expressed on the plasma membrane of APC, could then serve to trap peptide in a stable complex. If this were the only mechanism accounting for enhanced peptide binding at low pH, one would predict that there should be a concordance between the pH conditions required for enhanced binding and those associated with increased peptide dissociation. Furthermore, long-lived complexes of class II and peptide should not be observed at low pH without neutralization. In the present communization, I provide the data that support the generality of my previous conclusion that both affinity and maximal binding are regulated by pH in experiments using purified class II and biotin-labeled peptides. The pH profile for binding and dissociation using three different class II glycoproteins was analyzed, and the results demonstrated that enhanced binding is not coupled to enhanced dissociation. Peptide complexes were observed to be quite stable at pH 4.5 and above. This result was further substantiated in experiments where biotin peptide/class II complexes were extensively dialyzed at low pH followed by analysis on Western blots probed with avidin. Finally, a low pH assay system was devised to analyze the formation of stable peptide/class II complexes without pH neutralization. Our results indicate that stable complexes can be formed at low pH without the requirement for a shift to neutral pH. PMID- 1512544 TI - Exogenously-induced, natural killer cell-mediated neuronal killing: a novel pathogenetic mechanism. AB - Many human neurodegenerative diseases are characterized by the idiopathic death of cells narrowly restricted to a subset of neurons in a specific functional neuroanatomic system. Few in vivo models exist for the analysis of these types of degeneration. This report documents the death of sympathetic neurons resident in the superior cervical ganglia of rats after exposure to an exogenous chemical agent, the drug guanethidine, as being mediated by natural killer (NK) cells. This is the first in vivo model of a disorder of the nervous system in which NK cells appear to be the principal effector cell, and thus could serve a central role in dissecting the normal and pathological function of NK cells. In addition, this pathogenetic mechanism appears to represent a novel type of autoimmune reaction that could have a direct bearing on a number of human illnesses. PMID- 1512545 TI - Monocyte-selective transendothelial migration: dissection of the binding and transmigration phases by an in vitro assay. AB - We describe a quantitative assay of transendothelial migration (TEM) that allows us to selectively study the interaction of monocytes with confluent human endothelial cell (HEC) monolayers. The HEC are grown on hydrated collagen gels; the monocytes need not be purified. 100% of monocytes transmigrated the monolayer within 1 h at 37 degrees C and accumulated in the subendothelial collagen; TEM of lymphocytes was not detected within this time. Migration of neutrophils from the same donor was much slower and incomplete, with only 14% of PMN transmigrating in 2 h. This rapid TEM occurs in the absence of exogenous chemoattractants, and HEC in this system do not express cytokine-inducible leukocyte adhesion molecules. A slight modification of the TEM assay allowed us to separate binding to the apical HEC surface from TEM. We found that tight apical surface binding was the rate limiting step for TEM. Two-thirds of this binding and TEM could be blocked by a monoclonal antibody against the leukocyte beta 2 integrin chain CD18. This assay will allow us to dissect the mechanisms of both the binding and transmigration stages of diapedesis. PMID- 1512546 TI - Functionally conformed free class I heavy chains exist on the surface of beta 2 microglobulin negative cells. AB - Cytotoxic T lymphocytes (CTL) can recognize antigenic peptides bound in a groove formed by the alpha 1 and alpha 2 domains of the heterodimeric major histocompatibility complex class I molecule. Proper assembly, transport, and stability of functional class I molecules is thought to require beta 2 microglobulin (beta 2m), the light chain of the class I heterodimer. We show here that the requirement for beta 2m is not absolute. beta 2m- cells can be stained by the Db alpha 1 domain-specific B22-249.1 monoclonal antibody, which detects a conformation-dependent epitope. Furthermore, beta 2m- Con A blast target cells can be lysed by alloreactive CTL, even in serum-free conditions. Contrary to previous reports, the expression of low levels of conformed Db heavy (H) chains is a property to both normal and transformed beta 2m- cells. Finally, we present evidence that a subset of properly conformed H chains, free of beta 2m, may have almost equal representation on beta 2m+ and beta 2m- cells. PMID- 1512547 TI - Studies on T cell maturation on defined thymic stromal cell populations in vitro. AB - We describe an in vitro system in which positive selection of developing T cells takes place on defined stromal cell preparations, which include major histocompatibility complex class II+ epithelial cells but exclude cells of bone marrow origin. In this system, maturation of double-positive T cell receptor negative (TCR-), CD4+8+ thymocytes into single-positive TCR+, CD4+ and CD8+ cells takes place together with the development of functional competence. As in vivo, this maturation is associated with the upregulation of TCR levels as cells progress from double-positive to single-positive status. We also show that class II+ epithelial cells in these cultures are less efficient than dendritic cells in mediating the deletion (negative selection) of V beta 8+ cells by the superantigen staphylococcal enterotoxin B. For the first time, this approach provides a model in which the cellular interactions involved in both positive and negative selection can be studied under controlled in vitro conditions. PMID- 1512549 TI - T cell lines characterize events in the pathogenesis of the Wiskott-Aldrich syndrome. AB - The Wiskott-Aldrich syndrome (WAS) is a severe immunodeficiency and platelet deficiency disease arising from an X-linked defect. The disease is correctable by transplantation of hematopoietic stem cells, but the product of the defective gene is unidentified and the number of defects in patient blood cells is large. The current hurdle is the need to identify the early pathogenic event(s) that are the cause of other defects. As a step toward this goal, we have generated and examined a panel of interleukin 2-dependent allospecific T cell lines from peripheral lymphocytes of seven WAS patients and five normal individuals. WAS cell lines, like normal lines, undergo vigorous proliferation when challenged with specific allostimulant or with phorbol myristate acetate and ionomycin. Both normal and WAS T cell lines express cell surface molecules CD2, CD3, T cell receptor-alpha/beta, human histocompatibility leukocyte antigen class I, CD45 and CD11a, and varying ratios of CD4 and CD8, and are negative for natural killer cell and monocyte surface molecules. WAS T cell lines express CD43 (sialophorin/leukosialin) with molecular weight and in an amount comparable with normal T cell lines. WAS T cell lines thus do not express defects in CD43 (decreased amount, abnormal molecular weight), previously documented in WAS circulating lymphocytes. On the other hand, as detected by scanning electron microscopy, WAS cell lines exhibit severe morphological abnormalities, including decreased size and density of the microvillus surface projections. The morphological abnormalities of WAS T cell lines are similar to, or more extensive than, those previously reported for WAS peripheral lymphocytes, indicating that the generation of morphological (cytoarchitectural) defects is an early pathogenic event in this disease. The findings suggest that the gene that is defective in the WAS encodes a protein that normally functions to maintain or regulate the cytoskeletal structure of blood cells. PMID- 1512548 TI - Generation and analysis of random point mutations in an antibody CDR2 sequence: many mutated antibodies lose their ability to bind antigen. AB - We have investigated the impact of mutations on the binding functions of the phosphocholine (PC)-specific T15 antibody in the absence of antigen selection pressure. The H chain complementarity determining region 2 (CDR2) sequence of T15 antibody was saturated with point mutations by in vitro random mutagenesis. From the mutant library, 289 clones were screened by direct DNA sequencing. The point mutations generated by this method were randomly distributed throughout the CDR2 region and included all kinds of substitutions. 46 unique mutant antibodies, containing one to four point mutations each, were expressed in SP2/0 myeloma cells. Functional analysis on these antibodies has provided insights into several aspects of somatic mutation. (a) The majority (26/46) of mutant antibodies either lost (20/46) or had reduced (6/46) ability to bind PC-protein conjugates or R36a, a PC-expressing strain of Streptococcus pneumoniae. In contrast, none of the mutant antibodies displayed increased binding for these PC antigens. Taken together with calculations of destructive mutations elsewhere in the V region, the data suggest that somatic mutation may cause extensive wastage among B cells during clonal expansion after antigen stimulation. (b) The frequency of binding loss mutants increased sharply when a second mutation was introduced into the CDR2 sequence; it appears that, in some cases, two or more mutations are needed to destroy binding. (c) The mutant antibodies were tested for their reactivity to 11 non-PC antigens as well as to three PC analogues. None of the mutants gained new reactivity or changed their ability to discriminate structural analogues, supporting the notion that the major role of somatic mutation is to increase or decrease affinity rather than to create new specificities. (d) Mutations in at least five different positions in CDR2 were deleterious, suggesting that these residues may be essential for antigen binding. Three of these positions are novel in that they had not been identified to be important for binding PC by previous crystallographic analysis. (e) Introduction of mutations into two highly conserved residues in CDR2 did not alter the overall conformation of the V region as judged by antiidiotypic analysis, and, in some cases, did not affect the antigen binding function. The results thus indicate that even nonconservative substitutions of invariant residues need not be deleterious, suggesting that their conservation may be due to reasons other than maintaining antibody structure or specificity. PMID- 1512550 TI - Human T cells cannot act as autonomous antigen-presenting cells, but induce tolerance in antigen-specific and alloreactive responder cells. AB - The ability of two HLA-DR-expressing human T cell clones to function as antigen presenting cells (APC) was investigated using highly purified T cells. The results demonstrated that these T cell clones are unable to act as autonomous APC, and that recognition of nominal or alloantigens on the surface of T cells leads to a state of nonresponsiveness. The first observation was that a T cell clone with specificity for the 306-324 peptide of influenza hemagglutinin (HA), and raised from a DR1 responder, exhibited apparent degeneracy of major histocompatibility complex restriction when cultured with peptide in the presence of peripheral blood mononuclear cells (PBMC) expressing a wide variety of structurally unrelated DR types. However, when the PBMC were pulsed with peptide and washed before coculture with the clone, peptide was exclusively recognized with DR1Dw1. This implied that in the presence of soluble peptide the T cells were displaying ligand to each other, and that the third-party APC were providing costimulatory signals. To test the ability of T cells to act as autonomous APC, accessory cell-free preparations of two DR1-restricted clones were cultured with peptide in the presence or the absence of added B cell APC. T cell purity was established by the absence of proliferation in response to the mitogen phytohemagglutinin (PHA). PHA-nonresponsive T cells were completely unable to proliferate in response to peptide alone; furthermore, preculture of the HA specific clone, in the complete absence of accessory cells, with the same concentration of peptide (1 microgram/ml) that induced optimal proliferation when presented by conventional APC, led to profound nonresponsiveness. The same phenomenon was also observed when two of three anti-DR1 alloreactive T cell clones were precultured with a DR1-expressing T cell clone. The ability of the DR1-expressing clone to induce nonresponsiveness in anti-DR1 clones correlated with recognition of the DR1 alloantigen on the DR1-expressing clone. PMID- 1512551 TI - Clostridium perfringens enterotoxin is a superantigen reactive with human T cell receptors V beta 6.9 and V beta 22. AB - Candidate superantigens were screened for their ability to induce lysis of human histocompatibility leukocyte antigen class II-positive targets by human CD8+ influenza-specific cytotoxic T cell (CTL) lines. Clostridium perfringens enterotoxin (CPET) induced major histocompatibility complex unrestricted killing by some but not all CTL lines. Using "anchored" polymerase chain reactions, CPET was shown to selectively stimulate peripheral blood lymphocytes bearing T cell receptor V beta 6.9 and V beta 22 in five healthy donors. V beta 24, V beta 21, V beta 18, V beta 5, and V beta 6.1-5 appeared to be weakly stimulated. Antigen processing was not required for CPET to induce proliferation. Like the staphylococcal enterotoxins, CPET is a major cause of food poisoning. These data suggest that superantigenic and enterotoxigenic properties may be closely linked. PMID- 1512552 TI - Inhibition of proliferation of normal and transformed neural cells by blood group related oligosaccharides. AB - A synthetic tetrasaccharide structurally related to blood groups and selectin ligands inhibited division of astrocytes, gliomas, and neuroblastomas at micromolar concentrations. The compound was cytostatic for primary astrocytes in culture, but cytotoxic for fast proliferating cell lines. PMID- 1512553 TI - Cytosolic protein concentration is the primary volume signal for swelling-induced [K-Cl] cotransport in dog red cells. AB - Chloride-dependent K transport ([K-Cl] cotransport) in dog red cells is activated by cell swelling. Whether the volume signal is generated by a change in cell configuration or by the dilution of some cytosolic constituent is not known. To differentiate between these two alternatives we prepared resealed ghosts that, compared with intact red cells, had the same surface area and similar hemoglobin concentration, but a greatly diminished volume. Swelling-induced [K-Cl] cotransport was activated in the ghosts at a volume (20 fl) well below the activation volume for intact cells (70 fl), but at a similar hemoglobin concentration (30-35 g dry solids per 100 g wet weight). Ghosts made to contain 40% albumin and 60% hemoglobin showed activation of [K-Cl] cotransport at a concentration of cell solids similar to intact cells or ghosts containing only hemoglobin. [K-Cl] cotransport in the resealed ghosts became quiescent at a dry solid concentration close to that at which shrinkage-induced Na/H exchange became activated. These results support the notion that the primary volume sensor in dog red cells is cytosolic protein concentration. We speculate that macromolecular crowding is the mechanism by which cells initiate responses to volume perturbation. PMID- 1512554 TI - Effects of low myoplasmic Mg2+ on calcium binding by parvalbumin and calcium uptake by the sarcoplasmic reticulum in frog skeletal muscle. AB - The effects of low intracellular free Mg2+ on the myoplasmic calcium removal properties of skeletal muscle were studied in voltage-clamped frog skeletal muscle fibers by analyzing the changes in intracellular calcium and magnesium due to membrane depolarization under various conditions of internal free [Mg2+]. Batches of fibers were internally equilibrated with cut end solutions containing two calcium indicators, antipyrylazo III (AP III) and fura-2, and different concentrations of free Mg2+ (25 microM-1 mM) obtained by adding appropriate total amounts of ATP and magnesium to the solutions. Changes in AP III absorbance were used to monitor [Ca2+] and [Mg2+] transients, whereas fura-2 fluorescence was mostly used to monitor resting [Ca2+]. Shortly after applying an internal solution containing less than 60 microM free Mg2+ to the cut ends of depolarized fibers most of the fibers exhibited spontaneous repetitive movements, suggesting that free internal Mg2+ might affect the activity of the sarcoplasmic reticulum (SR) calcium channels at rest. The spontaneous contractions generally subsided. In polarized fibers the maximal amplitude of the calcium transient elicited by a depolarizing pulse was about the same whatever the internal [Mg2+], but its decay after the end of the pulse slower in low [Mg2+]. In low [Mg2+] (less than 0.14 mM), the mean rate constant of decay obtained from fitting a single exponential plus a constant to the decay of the calcium transients was approximately 30% of its value in the control fibers (1 mM internal [Mg2+]). A model characterizing the main calcium removal properties of a frog skeletal muscle fiber, including the SR pump and the Ca-Mg sites on parvalbumin, was fitted to the decay of the calcium transients. Results of the fits show that in low internal [Mg2+] the slowing of the decay of the calcium transient can be well predicted by both a decreased rate of SR calcium uptake and an expected decreased resting magnesium occupancy of parvalbumin leading to a reduced contribution of parvalbumin to the overall rate of calcium removal. These results are thus consistent with the known properties of parvalbumin as a Ca-Mg buffer and furthermore suggest that in an intact portion of a muscle fiber, the activity of the SR calcium pump can be affected by the level of free Mg2+. PMID- 1512555 TI - Low myoplasmic Mg2+ potentiates calcium release during depolarization of frog skeletal muscle fibers. AB - The role of intracellular free magnesium concentration ([Mg2+]) in modulating calcium release from the sarcoplasmic reticulum (SR) was studied in voltage clamped frog cut skeletal muscle fibers equilibrated with cut end solutions containing two calcium indicators, fura-2 and antipyrylazo III (AP III), and various concentrations of free Mg2+ (25 microM-1 mM) obtained by adding appropriate total amounts of ATP and magnesium to the solutions. Changes in AP III absorbance were used to monitor calcium transients, whereas fura-2 fluorescence was used to monitor resting calcium. The rate of release (Rrel) of calcium from the SR was calculated from the calcium transient and found to be increased in low internal [Mg2+]. After correcting for effects of calcium depletion from the SR and normalization to SR content, the mean values of the inactivatable and noninactivatable components of Rrel were increased by 163 and 46%, respectively, in low Mg2+. Independent of normalization to SR content, the ratio of inactivatable to noninactivatable components of Rrel was increased in low internal [Mg2+]. Both observations suggest that internal [Mg2+] preferentially modulates the inactivatable component of Rrel, which is thought to be due to calcium-induced calcium release from the SR. This could also explain the observation that, in low internal [Mg2+], the time to the peak of the calcium transient for a 5-ms depolarizing pulse was not very different from the time to the peak of the delta [Ca2+] for a 10-ms pulse of the same amplitude. Finally, in low internal [Mg2+], the calcium transient elicited by a short depolarizing pulse was in some cases clearly followed by a very slow rise of calcium after the end of the pulse. The observed effects of reduced [Mg2+] on calcium release are consistent with a removal of the inhibition that the normal 1 mM myoplasmic [Mg2+] exerts on calcium release in skeletal muscle fibers. PMID- 1512556 TI - Visual responses in teleosts. Electroretinograms, eye movements, and circadian rhythms. AB - We have recorded ocular potentials in response to brief flashes of light from two teleosts, the white perch (Roccus americana) and the green sunfish (Lepomis cyanellus). The animals were respired and maintained in an alert state for up to 2 d. Responses were recorded with corneal and transcleral electrodes. The responses of green sunfish were composed of electroretinogram (ERG) and eye movement potentials, whereas the responses in white perch contained only the ERG. Injection of curare abolished the sunfish eye movement potentials, unmasking the ERG. Observation under infrared illumination established a direct relationship between eye movements and the fast potentials which could be abolished by curare. We found no evidence of circadian changes in the amplitude of the ERG b-wave of either species. However, our results combined with those of a previous study of sunfish ocular potentials (Dearry, A., and B. Barlow, Jr. 1987. J. Gen. Physiol. 89: 745-770) suggest that the sunfish visual system exhibits rhythmic changes in oculomotor responses, which appear to be controlled by a circadian oscillator. PMID- 1512557 TI - Electroretinograms and circadian rhythms in green sunfish. PMID- 1512558 TI - Modulation of voltage-dependent Ca channel current by arachidonic acid and other long-chain fatty acids in rabbit intestinal smooth muscle. AB - The effects of arachidonic acid (AA) and other long-chain fatty acids on voltage dependent Ca channel current (ICa) were investigated, with the whole cell patch clamp method, in longitudinal smooth muscle cells of rabbit ileum. 10-30 microM AA caused a gradual depression of ICa. The inhibitory effect of AA was not prevented by indomethacin (10 microM) (an inhibitor of cyclooxygenase) or nordihydroguaiaretic acid (10 microM) (an inhibitor of lipoxygenase). 1-(5 Isoquinolinesulfonyl)-2-methylpiperazine (H7; 25-50 microM) or staurosporine (2 microM) (inhibitors of protein kinase C) did not block the AA-induced inhibition of ICa, and application of phorbol ester (a protein kinase C activator) (phorbol 12,13-dibutyrate, 0.2 microM) did not mimic the AA action. Some other cis unsaturated fatty acids (palmitoleic, linoleic, and oleic acids) were also found to depress ICa, while a trans-unsaturated fatty acid (linolelaidic acid) and saturated fatty acids (capric, lauric, myristic, and palmitic acids) had no inhibitory effects on ICa. Myristic acid consistently increased the amplitude of ICa at negative membrane potentials. The present results suggest the possible role of AA, and perhaps other fatty acids, in the physiological and/or pathological modulation of ICa in smooth muscle. PMID- 1512559 TI - lux genes and the applications of bacterial bioluminescence. PMID- 1512560 TI - Functional expression in Escherichia coli of proteins B and C from soluble methane monooxygenase of Methylococcus capsulatus (Bath). AB - Methylococcus capsulatus (Bath) uses a soluble methane monooxygenase (sMMO) to catalyse the oxidation of methane to methanol. sMMO is comprised of three components; A, B and C. Protein C (the reductase) transfers electrons from NADH to protein A (the hydroxylase) which contains the active site, and protein B regulates this electron flow. The five genes encoding the sMMO proteins and their subunits are clustered and have been cloned in Escherichia coli. A DNA fragment containing mmoB, the gene encoding protein B, was subcloned into pT7-5, a plasmid of the T7 RNA polymerase promoter expression system. Upon induction, E. coli expressed protein B which was fully functional after purification. The gene encoding protein C, mmoC, was amplified with unique restriction sites at each end using the polymerase chain reaction and then subcloned into pT7-7 (a plasmid similar to pT7-5 but containing its own ribosome-binding site and ATG start codon). Protein C expressed in E. coli was also found to be functional. This is the first report of the functional expression of methanotroph methane monooxygenase genes in a heterologous host and represents a significant step forward in our analysis of the assembly and catalysis of sMMO. PMID- 1512561 TI - A monofunctional prephenate dehydrogenase created by cleavage of the 5' 109 bp of the tyrA gene from Erwinia herbicola. AB - A cohesive phylogenetic cluster that is limited to enteric bacteria and a few closely related genera possesses a bifunctional protein that is known as the T protein and is encoded by tyrA. The T-protein carries catalytic domains for chorismate mutase and for cyclohexadienyl dehydrogenase. Cyclohexadienyl dehydrogenase can utilize prephenate or L-arogenate as alternative substrates. A portion of the tyr A gene cloned from Erwinia herbicola was deleted in vitro with exonuclease III and fused in-frame with a 5' portion of lacZ to yield a new gene, denoted tyrA*, in which 37 N-terminal amino acids of the T-protein are replaced by 18 amino acids encoded by the polycloning site/5' portion of the lacZ alpha peptide of pUC19. The TyrA* protein retained dehydrogenase activity but lacked mutase activity, thus demonstrating the separability of the two catalytic domains. While the Km of the TyrA* dehydrogenase for NAD+ remained unaltered, the Km for prephenate was fourfold greater and the Vmax was almost twofold greater than observed for the parental T-protein dehydrogenase. Activity with L arogenate, normally a relatively poor substrate, was reduced to a negligible level. The prephenate dehydrogenase activity encoded by tyrA* was hypersensitive to feedback inhibition by L-tyrosine (a competitive inhibitor with respect to prephenate), partly because the affinity for prephenate was reduced and partly because the Ki value for L-tyrosine was decreased from 66 microM to 14 microM. Thus, excision of a portion of the chorismate mutase domain is shown to result in multiple extra-domain effects upon the cyclohexadienyl dehydrogenase domain of the bifunctional protein.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1512562 TI - Lack of homology between two haloacetate dehalogenase genes encoded on a plasmid from Moraxella sp. strain B. AB - Two genes encoding haloacetate dehalogenases, H-1 and H-2, are closely linked on a plasmid from Moraxella sp. strain B. H-1 predominantly acts on fluoroacetate, but H-2 does not. To elucidate the molecular relationship between the two enzymes, we compared their structural genes. Two restriction fragments of the plasmid DNA were subcloned on M13 phages and their nucleotide sequences were determined. The sequence of each fragment contained an open reading frame that was identified as the structural gene for each of the two dehalogenases on the basis of the following criteria; N-terminal amino acid sequence, amino acid composition, and molecular mass. The genes for H-1 and H-2, designated dehH1 and dehH2, respectively, had different sizes (885 bp and 675 bp) and G+C contents (58.3% and 53.4%). Sequence analysis revealed no homology between the two genes. We concluded that the dehalogenases H-1 and H-2 have no enzyme-evolutionary relationship. The deduced amino acid sequence of the dehH1 gene showed significant similarity to those of three hydrolases of Pseudomonas putida and a haloalkane dehalogenase of Xanthobacter autotrophicus. The dehH2 coding region was sandwiched between two repeated sequences about 1.8 kb long, which might play a part in the frequent spontaneous deletion of dehH2 from the plasmid. PMID- 1512563 TI - Molecular genetics of the extracellular lipase of Pseudomonas aeruginosa PAO1. AB - The structural gene (lipA) coding for the extracellular lipase of Pseudomonas aeruginosa PAO1 has been cloned on plasmid pSW118. Nucleotide sequence analysis revealed a gene of 936 bp. lipA codes for a proenzyme of 311 amino acids including a leader sequence of 26 amino acids. The mature protein was predicted to have a M(r) of 30134, an isoelectric point of 5.6, and a consensus sequence (IGHSHGG) typical of lipases. Furthermore it is highly homologous (greater than 60%) to other lipases from various pseudomonads. The lipA gene failed to hybridize detectably with genomic DNA from other Pseudomonas species except P. alcaligenes, even under relaxed stringency. Located 220 bp downstream of the lipA gene, is an open reading frame (ORF2, lipH) which encodes a hydrophilic protein (283 amino acids; M(r) 33587) that shows some homology to the limA gene product of P. cepacia. In complementation tests of lipase-defective mutants, lipH was shown to be necessary for expression of active extracellular lipase in P. aeruginosa PAO1. PMID- 1512564 TI - A survey of Col plasmids in natural isolates of Escherichia coli and an investigation into the stability of Col-plasmid lineages. AB - A survey of colicins in the ECOR reference collection of Escherichia coli is presented. Twenty-five of the 72 ECOR strains exhibited a phenotype consistent with colicin production and E. coli isolated from human hosts were more likely to be colicinogenic than those from animal hosts. Multiple representatives of two Col plasmids, low-molecular-mass ColE1 plasmids and high-molecular-mass, conjugative ColIa plasmids were isolated from the ECOR collection and were examined with a combination of restriction fragment and Southern analysis. These data suggested that ColE1 plasmids comprise a stable (cohesive) plasmid lineage, while ColIa plasmids represent a family of distinct plasmid lineages united by the presence of the colicin Ia operon. PMID- 1512565 TI - Cloning, sequencing and expression of the gene encoding the cell-envelope associated proteinase from Lactobacillus paracasei subsp. paracasei NCDO 151. AB - The gene encoding the cell-envelope-associated proteinase of Lactobacillus paracasei subsp. paracasei NCDO 151 (formerly Lactobacillus casei NCDO 151) was cloned and sequenced. The gene was located on the chromosome and encoded a polypeptide of 1902 amino acids. The proteinase is N-terminally cleaved upon maturation. It shows extensive homology to the Lactococcus lactis subsp. cremoris Wg2 proteinase. Similar to the situation in Lactococcus, a maturation gene was found upstream of the proteinase gene. The cloned proteinase gene was expressed in Lactobacillus plantarum. However, no expression was observed when the gene was cloned in Lactococcus lactis. PMID- 1512566 TI - Molecular cloning and characterization of an alkalophilic Bacillus sp. C125 gene homologous to Bacillus subtilis sec Y. AB - A 1.8 kb HindIII DNA fragment containing the secY gene of alkalophilic Bacillus sp. C125 has been cloned into plasmid pUC119 using the B. subtilis secY gene as a probe. The complete nucleotide sequence of the cloned DNA indicated that it contained one complete ORF and parts of two other ORFs. The similarity of these ORFs to the sequences of the B. subtilis proteins indicated that they were the genes for ribosomal protein L15-SecY-adenylate kinase, in that order. The gene product of the alkalophilic Bacillus sp. C125 secY homologue was composed of 431 amino acids and its M(r) value has been calculated to be 47,100. The distribution of hydrophobic amino acids in the gene product suggested that the protein was a membrane integrated protein with ten transmembrane segments. The total amino acid sequence of alkalophilic Bacillus sp. C125 secY homologue showed 69.7% homology with that of B. subtilis secY. Regions of remarkably high homology (78% identity) were present in transmembrane regions, and cytoplasmic domains (73% identity) with less homologous regions present in extracellular domains (43% identity). PMID- 1512567 TI - Stable inheritance of shuttle vectors based on plasmid pIM13 in a mutant strain of Clostridium acetobutylicum. AB - New shuttle vectors for Clostridium acetobutylicum were constructed, using as replicons the Gram-positive plasmid pIM13, and derivatives of the Gram-negative plasmid pBR322, including pUC19. These vectors transformed C. acetobutylicum at a high frequency (up to 10(6) transformants per microgram DNA) by PEG-mediated protoplast transformation. A mutant host strain, NI-4082, was isolated on the basis of its ability to maintain plasmid pIM13 stably in the absence of selection pressure. The shuttle vectors showed no segregational or structural instability in this mutant strain. Moreover, the results suggested a relationship between segregational instability and the multimerization of pIM13 in C. acetobutylicum. The host/vector system described possessed all the properties required for efficient gene cloning in this species. PMID- 1512568 TI - Isolation and characterization of a conjugative plasmid from Legionella pneumophila. AB - The conjugative properties of an indigenous 85 MDa plasmid (designated pCH1) from Legionella pneumophila were studied. To determine if pCH1 was transmissible by conjugation, mating experiments were performed between legionellae that harboured pCH1 and several plasmid-less recipients. Plasmid transfer was monitored by colony hybridization, using a cloned 21.0 kb SalI restriction fragment from pCH1 as a probe. The results from these experiments showed that pCH1 could be conjugatively transferred into several strains of L. pneumophila serogroup 1 but not into strain Bloomington-2 (serogroup 3) or Escherichia coli. Southern hybridization experiments in which pCH1 DNA was used as a probe showed that pCH1 does not share homology with other indigenous L. pneumophila plasmids. There was no detectable DNA homology between pCH1 and L. pneumophila chromosomal DNA. Additional mating experiments revealed that pCH1 was unable to mobilize the L. pneumophila chromosome. The conjugative transfer of pCH1 into plasmid-less avirulent or virulent serogroup 1 strains did not alter the intracellular growth characteristics of these strains in U937 cells, a human-monocyte-like cell line, or in the amoeba Hartmannella vermiformis. These results suggest that pCH1 does not contribute to the ability of L. pneumophila to enter or grow within eukaryotic cells. PMID- 1512569 TI - Characterization of bacteriophage BFK20 from Brevibacterium flavum. AB - Bacteriophage BFK20 was isolated from a Brevibacterium flavum strain that had become contaminated during industrial fermentation. BFK20 has a polyhedral head 50 nm wide and a non-contractile tail 200 nm long and 10 nm in diameter. The genome of this bacteriophage consists of a linear double stranded DNA molecule of 44-45 kb with cohesive ends. The capsid of phage BFK20 contains nine polypeptides with molecular masses from 22.0-108.0 kDa. BFK20 DNA was used as a donor for fragments carrying promoters and transcription-terminators. PMID- 1512570 TI - Molecular characterization of two bacteriophages isolated from Desulfovibrio vulgaris NCIMB 8303 (Hildenborough). AB - A preliminary endonuclease restriction map of a bacteriophage isolated from Desulfovibrio vulgaris has been established. BamHI cleaved whole phage DNA into four fragments while HindIII cut the same DNA into seven fragments. Mapping studies succeeded in linking the four BamHI fragments into two DNA segments; however, no linkage between the two segments was detected. These data imply that two phages were induced from cultures of D. vulgaris and that the two segments represented the DNA from these phages. Support for this hypothesis came from size approximation of restriction enzyme fragments, electron micrographs, and density gradients. PMID- 1512571 TI - Molecular characterization of the genes encoding acetohydroxy acid synthase in the cyanobacterium Spirulina platensis. AB - The enzyme acetohydroxy acid synthase (AHS), which catalyses the first common step in the biosynthesis of isoleucine, leucine and valine, has been demonstrated to be present in Spirulina platensis in two isoenzymic forms. The complete nucleotide sequences of the genes ilvX and ilvW encoding these two enzymes have been determined. Sequence analysis revealed the presence of two open reading frames, of 1836 and 1737 nucleotides for ilvX and ilvW, respectively. The predicted amino acid sequences of the two isoenzymes, compared with the Synechococcus PCC 7942 AHS enzyme and the large subunits of the Escherichia coli AHSI, II, III isoenzymes, revealed a notable degree of similarity. A small subunit has not been identified for either of the S. platensis AHS isoenzymes. Analysis by Northern blot hybridization demonstrated that the ilvX and ilvW genes are transcribed to give mRNA species of approximately 2.15 kb and 1.95 kb, respectively. PMID- 1512572 TI - Generation of genetic recombinants in Trichosporon cutaneum by spontaneous segregation of protoplast fusants. AB - Auxotrophic mutants were isolated in two strains of Trichosporon cutaneum. Complementing auxotrophs were hybridized by protoplast fusion. Some of the fusants were apparently transient diploids and segregated to give recombinant marker combinations. PMID- 1512573 TI - Cloning and expression of multiple cellulase cDNAs from the anaerobic rumen fungus Neocallimastix patriciarum in Escherichia coli. AB - A cDNA expression library of the rumen fungus Neocallimastix patriciarum was made in Escherichia coli. Cellulolytic clones were identified by screening on a medium containing carboxymethylcellulose. Restriction mapping and Southern hybridization analysis of selected clones revealed three distinct cellulase cDNAs, designated celA, celB and celC. Studies on the substrate specificity showed that the enzyme encoded by celA had high activity towards amorphous and microcrystalline cellulose, while the celB and celC enzymes had relatively high activity on carboxymethylcellulose, with little activity on microcrystalline cellulose. Analysis of hydrolysis products from defined cellodextrins showed that the celB and celC enzymes hydrolysed beta-1,4-glucosidic linkages randomly, whereas the celA enzyme cleaved cellotetraose to cellobiose, and cellopentaose to cellobiose and cellotriose. Cellobiose was also the only product detectable from hydrolysis of microcrystalline cellulose by the celA enzyme. Based on substrate specificity and catalytic mode, celA appears to encode a cellobiohydrolase, while celB and celC encode endoglucanases. Northern blot hybridization analysis showed that expression of the three cellulase transcripts in N. patriciarum was induced by cellulose. PMID- 1512574 TI - Regulation of restrictocin production in Aspergillus restrictus. AB - The production of restrictocin (a cytotoxin that specifically cleaves ribosomal RNA) by cultures of Aspergillus restrictus grown in liquid medium was investigated. The function of restrictocin, the method of its accumulation and the mode of resistance to restrictocin in A. restrictus are unknown. Previous studies have indicated that restrictocin accumulates in the medium with culture age. These observations have been extended in this study by cloning the cDNA of the res gene and using this cDNA clone to probe the onset of messenger RNA synthesis in the cells. The results of the Northern analysis were compared to the production and accumulation of restrictocin and morphological differentiation of the cells in culture. Restrictocin was found in the medium at the same time that mRNA was detected in the cells. This suggests that the leader sequence encoded by the cDNA provides an efficient secretion system for the protein. Both the protein and the mRNA were detected coincident with the formation of differentiated cell structures. These structures develop into conidiophores with one layer of sterigmata and conidia forming from the sterigmata. These results suggest that restrictocin is either involved in the process of conidiation or is coordinately regulated with differentiation leading to conidiation. PMID- 1512575 TI - Production and localization of restrictocin in Aspergillus restrictus. AB - The production and secretion of restrictocin (a cytotoxin that cleaves ribosomal RNA) by cultures of the fungus Aspergillus restrictus was investigated. Previous studies have indicated that restrictocin production in liquid culture coincides with the appearance of differentiated cell structures. A study of the correlation between the appearance of differentiated structures and restrictocin production was conducted with A. restrictus grown on agar medium. Restrictocin was found to be associated with the cell mass of the agar-grown culture (in contrast to liquid cultures), and was first observed when aerial hyphae emerged. Restrictocin levels increased until the time of conidiation, after which they fell off sharply. No restrictocin could be found in the agar medium. The presence of restrictocin upon and within various cell structures was determined by immunofluorescent laser microscopy. This study showed that restrictocin became localized to the conidiophores and phialides during the process of conidiation. Prior to this, restrictocin was found within the hyphae in localized concentrations that may correspond to secretory vesicles. PMID- 1512576 TI - Effect of nitrogen source on the levels of nitrate reductase in the yeast Hansenula anomala. AB - Levels of nitrate reductase (NR) protein in Hansenula anomala and Hansenula wingei were determined using specific antiserum raised against the enzyme from H. anomala. Extracts from nitrate-grown cells contained NR protein, while in those from cells grown on ammonium, glutamine or peptone, no cross-reacting material could be observed. Enzyme activity correlated with the levels of cross-reacting material. When nitrate was used as nitrogen source, NR was always present, even in cultures with ammonium, glutamine or peptone, although in these cases both the levels of activity and protein were lower. NR activity was consistently two to four times higher in cells grown in glucose than in cells grown in ethanol. Nitrate was required for NR induction, and deprivation of nitrate from nitrate grown cells resulted in a rapid loss of NR activity. PMID- 1512577 TI - Purification and characterization of L-2,4-diaminobutyrate decarboxylase from Acinetobacter calcoaceticus. AB - Acinetobacter calcoaceticus ATCC 23055 produces a large amount of 1,3 diaminopropane under normal growth conditions. The enzyme responsible, L-2,4 diaminobutyrate (DABA) decarboxylase (EC 4.1.1.-), was purified to electrophoretic homogeneity from this bacterium. The native enzyme had an M(r) of approximately 108,000, with a pI of 5.0, and was a dimer composed of identical or nearly identical subunits with apparent M(r) 53,000. The enzyme showed hyperbolic kinetics with a Km of 1.59 mM for DABA and 14.6 microM for pyridoxal 5'-phosphate as a coenzyme. The pH optimum was in the range 8.5-8.75, and Ca2+ gave a much higher enzyme activity than Mg2+ as a cationic cofactor. N-gamma-Acetyl-DABA, 2,3 diaminopropionic acid, ornithine and lysine were inert as substrates. The enzyme was different in subunit structure, N-terminal amino acid sequence and immunoreactivity from the DABA decarboxylase of Vibrio alginolyticus previously described. PMID- 1512578 TI - The use of rRNA sequences and fluorescent probes to investigate the phylogenetic positions of the anaerobic ciliate Metopus palaeformis and its archaeobacterial endosymbiont. AB - The polymerase chain reaction (PCR) was used to amplify small-subunit ribosomal DNA from the anaerobic ciliated protozoon Metopus palaeformis, and from its uncultured endosymbiotic bacteria. This was accomplished directly from total DNA extracted from protozoa without prior isolation or enrichment for symbiont cells. The double-stranded amplification products were precipitated and directly sequenced using the linear PCR reaction. Fluorescent oligonucleotide probes were designed and used in whole-cell hybridizations to provide direct visual evidence that the sequences originated from the host ciliate and from the endosymbiont. Phylogenetic analysis of the Metopus palaeformis sequence consistently placed it as a deep-branching lineage near the root of the ciliate tree. However, the present data were insufficient to resolve the detailed relationship between Blepharisma and Metopus and thus to determine if the heterotrichs are mono- or paraphyletic. Phylogenetic analysis of the symbiont partial sequence clearly demonstrated that it is an archaeobacterium and that it is closely related to, but distinct from, Methanobacterium formicicum. PMID- 1512579 TI - Identification of erythrocyte-binding antigens in Helicobacter pylori. AB - The surface antigens of Helicobacter pylori conferring erythrocyte-binding activity were obtained by adsorption onto formaldehyde-treated dog and goat erythrocytes from supernatant fractions of sonicated bacteria and elution using a high concentration of NaCl. The desorbed material was analysed by SDS-PAGE and immunoblotting with anti-whole-cell serum to agar-grown bacteria which had been absorbed with broth-grown, non-haemagglutinating cells (haemagglutination associated antiserum). Two polypeptides with molecular masses of 25 and 59 kDa were revealed as erythrocyte-binding antigens. Strains which agglutinated both dog and goat erythrocytes possessed both these erythrocyte-binding antigens, whereas an antigenically cross-reactive 24 kDa polypeptide was present in a strain which only agglutinated goat erythrocytes. Haemagglutinin material was extracted from H. pylori using n-octylglucopyranoside and purified by Sepharose chromatography and sucrose density gradient ultracentrifugation. The purified extract directly agglutinated erythrocytes in a neuraminyl-lactose-sensitive and neuraminidase-sensitive manner. The 59 kDa polypeptide was not present in the purified haemagglutinin preparation. The haemagglutination-associated antiserum reacted strongly with the 25 kDa polypeptide band which was the most prominent polypeptide band on analysis of the purified haemagglutinin preparation by SDS PAGE and silver staining. Thus, H. pylori possesses at least two adhesins, one of which recognises a N-acetylneuraminic acid (alpha 2-3) moiety of receptors, the other being of unknown receptor specificity. Differences in the antigenicity and molecular masses of these adhesins in individual strains may underlie differences in receptor-binding specificities and haemagglutination profiles. PMID- 1512580 TI - Binding of purified Bacillus sphaericus binary toxin and its deletion derivatives to Culex quinquefasciatus gut: elucidation of functional binding domains. AB - Highly larvicidal strains of Bacillus sphaericus produce a binary toxin composed of 51 and 42 kDa proteins which binds to sharply delineated regions of the gastric caecum and posterior midgut of susceptible larvae of the mosquito Culex quinquefasciatus. To investigate the role of the individual subunits and the organization of functional binding regions within the toxin, plasmids were constructed for the expression in Escherichia coli of the toxin proteins and their NH2- and COOH-terminal deletion derivatives as fusions with glutathione S transferase (GST). Toxin proteins were purified by affinity chromatography followed by cleavage from the GST carrier with thrombin. The LC50 values for the purified toxin proteins and their deletion derivatives were determined. The binding patterns of fluorescently labelled toxin suggested that the 51 kDa protein is the primary binding component of the toxin and mediates the regional binding and internalization of the 42 kDa protein. Examination of the toxin deletion derivatives revealed that the NH2-terminal region of the 51 kDa protein was required for binding to the larval gut, whilst the COOH-terminal region was responsible for interacting with the 42 kDa protein. Toxicity was strongly correlated with the subsequent internalization of the toxin, probably by endocytosis. PMID- 1512581 TI - Lack of correlation between colony morphology and lipooligosaccharide content in the Mycobacterium tuberculosis complex. AB - Rough and smooth colony variants of the Mycobacterium tuberculosis complex were compared with respect to their composition in trehalose-containing glycolipid antigens in view of the results of a recent investigation suggesting that the chemical basis of rough and smooth colony morphology in mycobacteria may reside in the occurrence of lipooligosaccharides. A careful chemical characterization of the individual glycolipids of the selected strains allowed the identification of the major glycolipids. The comparative study of the glycolipid content of the smooth Canetti strain, its spontaneous rough variant, and 16 additional strains of M. tuberculosis, M. bovis and M. africanum showed that the presence of lipooligosaccharides was not related to the morphology of the colonies. PMID- 1512582 TI - Verbal communication, nonverbal communication, and private speech in lower and middle socioeconomic status preschool children. AB - Three types of communication--verbal, nonverbal, and private speech--were investigated in 4- and 5-year-old children. Multiple analyses of variance (MANOVAs) without IQ controlled and multiple analyses of covariance (MANCOVAs) with IQ as a covariate were computed and followed by ANOVAs and ANCOVAs to determine the effects of sex, age, and socioeconomic status (SES) on each of these types of communication. The ANOVAs and the ANCOVAs yielded the same conclusions. Results indicated that age and SES, but not sex, influence the use of the three communication types. From age 4 to age 5, private speech decreased for middle SES children and remained the same for lower SES children. Although lower SES children had more nonverbal communication at both age levels than middle SES children, nonverbal communication decreased for middle SES children and increased for lower SES children between the ages of 4 and 5 years. Both lower and middle SES groups increased in verbal communication between the two ages. The middle SES 4-year-olds used more verbal communication than their lower SES counterparts, and the difference was maintained at age 5. Although IQ is related to verbal communication, statistically controlling for the effects of IQ did not change the conclusions. PMID- 1512583 TI - The influence of age, gender, and having a younger sibling on children's knowledge about babies. AB - This article reports on two studies designed to measure 4- to 7-year-old children's knowledge about babies and its relationship to gender role development. In Study 1, children were asked several questions about babies and were given the Sex Role Learning Index (SERLI; Edelbrock & Sugawara, 1978). Girls provided more answers to one question, and children with younger siblings provided more answers to another. Overall, however, there were few relationships between knowledge about babies and gender role development. The second study measured knowledge about babies with two measures. The first measure asked children to identify foods that babies could eat and activities babies were capable of doing. The second measure asked children to identify the names and uses of certain objects. Older children scored higher on the foods and activities measure. Children who had younger siblings performed better on the objects measure. Gender and gender role development showed little relationship to knowledge about babies. PMID- 1512584 TI - Visual and auditory orienting responses in preterm infants: a comparison of three cohorts over time. AB - Visual and auditory orienting responses were compared in three cohorts of preterm infants (N = 351) born between 1977 and 1987. The infants were divided into one group born between 25 and 34 weeks gestational age (n = 140) and one group born between 35 and 37 weeks gestational age (n = 211). Ratings were made of the infants' best orienting responses to a bull's-eye, rattle, bell, voice, and face plus voice combined. Analyses of covariance were computed to adjust for changes in perinatal variables between 1977 and 1987. For both groups, there were significant differences between cohorts on orienting to the bull's-eye, with a trend for the 25- to 34-week group on orienting to the rattle. Behavioral outcome for preterm infants has improved with changes in neonatal intensive care. PMID- 1512585 TI - Effects of real gender and labeled gender on adults' perceptions of infants. AB - Three experiments were conducted to discover factors mediating adults' perceptions of male and female infants. In the first experiment, college students were shown 30-s videotapes of four male and four female babies, each of whom was randomly labeled with a male or a female name. Infants labeled as male were perceived as significantly more masculine and stronger than those labeled as female. Discriminant analyses revealed that both rated masculinity and the combination of ratings on male stereotyped traits differentiated infants labeled as male or female. Analyses of real gender revealed that boys were rated as less sensitive and stronger than girls. Discriminant analyses suggested that the combination of less sensitive, more of a problem, more mature, and more playful best differentiated real males from real females. In Experiment 2, the findings of Experiment 1 were confirmed with a sample of mothers of young infants. In Experiment 3 college students' judgments of the sex of the eight babies were correctly predicted from the sensitivity ratings of these babies in Experiment 1. It appears that there is a complex of cues from which adults make judgments of infants' gender and inferences about their characteristics: Boys may appear stronger, more playful, and more of a problem, and girls seem to look more sensitive. Implications for further studies of gender labeling and for sex typing are discussed. PMID- 1512586 TI - Meaning in life and psychological well-being: an empirical study using the Chinese version of the Purpose in Life questionnaire. AB - The Chinese version of the Purpose in Life questionnaire (C-PIL) was administered to 2,150 Chinese secondary school students, along with other instruments assessing psychiatric symptoms and positive mental health. Total C-PIL and its two subscales, Quality of Existence (QEXIST) and Purpose of Existence (PEXIST), correlated significantly with all measures of psychological well-being. Relative to PEXIST scores, QEXIST scores were found to be more predictive of psychological well-being. Subjects with different existential status (defined by high vs. low levels of QEXIST and PEXIST) were associated with different degrees of psychological well-being. The concept of meaning in life, as indexed by the C PIL, and the hypothesis that life meaning is related to psychological well-being require further elaboration and refinement. PMID- 1512587 TI - Parental conflict and male adolescent problem behavior. AB - Mothers in 30 clinical and 35 nonclinical families completed a behavior checklist for a target son and all other sons in the family who were between 13 and 17 years old. Each of these male adolescents completed two perceived parental conflict questionnaires for their biological parents. In each group, child behavior problems and parental conflict were correlated under two conditions: (a) using information pertaining to the target adolescent and (b) using information pertaining to the male adolescent experiencing the greatest behavior difficulties. Correlations increased in the nonclinical group when the information used was for the adolescent experiencing the greatest behavior difficulties. PMID- 1512588 TI - Girls' identity formation in the changing social structure of Sri Lanka. AB - Adolescent girls (N = 118) from diverse social backgrounds in Sri Lanka described their views of womanhood. Qualities of the ideal woman considered most important were kindness and honesty, liking children, intelligence, and having a good job. Although the traditional role of the Sri Lankan woman is that of homemaker, most girls in the study (55%) drew the ideal woman working outside the home, often as a teacher or a doctor. Nevertheless, adolescent girls emphasized traditional qualities of the woman at both work and home as self-sacrificing and serving others. PMID- 1512589 TI - Tutoring outcomes of academically underprepared adolescent minority students as a function of student and tutor characteristics. PMID- 1512590 TI - Does Spearman's g decline at high IQ levels? Some evidence from Scotland. PMID- 1512591 TI - Human absence epilepsies. AB - A historical review of the concept of absence seizures. Their clinical features are very suggestive but a diagnosis made solely on clinical grounds is not always safe. Comparable pitfalls exist in the interpretation of EEG patterns. Absence seizures belong to several epileptic syndromes. They are briefly described. PMID- 1512592 TI - Mapping of cerebral energy metabolism in rats with genetic generalized nonconvulsive epilepsy. AB - The quantitative 2-[14C]deoxyglucose autoradiographic method was applied to measure local cerebral metabolic rates of glucose (LCMRglc) in a model of genetic petit-mal-like seizures in a strain of Wistar rats. During the experimental period, epileptic rats exhibited synchronous spike-and-wave discharges, whereas the EEG pattern of control animals was normal. Overall, LCMRglc was consistently higher in epileptic rats than in the non-epileptic controls. The increase in LCMRglc was widespread and concerned all cerebral functional systems studied, whether they exhibit spike-and-wave discharges (neocortex and thalamus), or not (limbic system). These results are in good accordance with positron-emission tomography measurements in humans with typical childhood absence epilepsy. There appears to be a lack of anatomical correlation between areas demonstrating hypermetabolism and areas where spike-and-wave discharges are recorded. The administration of 200 mg/kg ethosuximide completely suppressed spike-and-wave discharges in epileptic rats and did not change the EEG pattern in controls. However, LCMRglc were increased to the same extent over control values in epileptic rats whether they were injected with ethosuximide or untreated. By contrast, when epileptic rats were given 2 mg/kg haloperidol, the frequency and the length of spike-and-wave discharges increased, inducing almost a permanent petit-mal status epilepticus. Haloperidol did not change EEG pattern in controls. In haloperidol-treated epileptic rats, LCMRglc decreased to levels comparable to those measured in untreated control rats. In the presence of haloperidol, LCMRglc were similar in both control and epileptic rats. Thus, the diffuse increase in cerebral energy metabolism in epileptic rats as compared to controls is not directly related to the occurrence of spike-and-wave discharges, and may rather be associated with inhibitory mechanisms involved in their termination and suppression, as well as their spread to limbic and motor structures. PMID- 1512593 TI - The tottering mouse: a critical review of its usefulness in the study of the neuronal mechanisms underlying epilepsy. AB - The tottering mouse resulted from a recessively inherited, autosomal, single locus mutation which produces a very characteristic neurological and cellular phenotype. Almost simultaneously and late in the development of this mutant appears a triad of symptoms: frequent episodes of absence seizures with spike-and wave discharges; more rarely occurring episodes of focal motor seizures; and ataxia. Electrographic, behavioural and pharmacological similarities to absence epilepsy in man make the tottering mouse a useful animal model for testing new anti-absence drugs. It also affords a unique opportunity to study the effects of multiple alleles on epileptic behaviour. The neuronal mechanisms underlying the generation of absence seizures in this mutant are apparently a combination of a generalized noradrenergic hyperactivity in the brain and some gene-linked, but unknown, conditions prevailing in an earlier phase of development at specific brain areas which induce the generalized forebrain hyper-innervation by locus coeruleus terminals. Several biochemically, microscopically and electrophysiologically identified cellular differences between normal and tottering mice are potential aspects of this primary developmental defect. Research into these gene-linked neuronal characteristics co-inherited with seizures in this mutant makes the tottering mouse a powerful tool in the study of cellular mechanisms underlying genetically determined factors in epileptogenesis. PMID- 1512594 TI - Genetic absence epilepsy in rats from Strasbourg--a review. AB - We have selected a strain of rats and designated it the Genetic Absence Epilepsy Rat from Strasbourg (GAERS). In this strain, 100% of the animals present recurrent generalized non-convulsive seizures characterized by bilateral and synchronous spike-and-wave discharges accompanied with behavioural arrest, staring and sometimes twitching of the vibrissae. Spontaneous SWD (7-11 cps, 300 1,000 microV, 0.5-75 sec) start and end abruptly on a normal background EEG. They usually occur at a mean frequency of 1.5 per min when the animals are in a state of quiet wakefulness. Drugs effective against absence seizures in humans (ethosuccimide, trimethadione, valproate, benzodiazepines) suppress the SWD dose dependently, whereas drugs specific for convulsive or focal seizures (carbamazepine, phenytoin) are ineffective. SWD are increased by epileptogenic drugs inducing petit mal-like seizures, such as pentylenetetrazol, gamma hydroxybutyrate, THIP and penicillin. Depth EEG recordings and lesion experiments show that SWD in GAERs depend on cortical and thalamic structures with a possible rhythmic triggering by the lateral thalamus. Most neurotransmitters are involved in the control of SWD (dopamine, noradrenaline, NMDA, acetylcholine), but GABA and gamma-hydroxybutyrate (GHB) seem to play a critical role. SWD are genetically determined with an autosomal dominant inheritance. The variable expression of SWD in offsprings from GAERS x control reciprocal crosses may be due to the existence of multiple genes. Neurophysiological, behavioural, pharmacological and genetic studies demonstrate that spontaneous SWD in GAERS fulfill all the requirements for an experimental model of absence epilepsy. As the mechanisms underlying absence epilepsy in humans are still unknown, the analysis of the genetic thalamocortical dysfunction in GAERS may be fruitful in investigations of the pathogenesis of generalized non-convulsive seizures. PMID- 1512595 TI - Cortical and thalamic lesions in rats with genetic absence epilepsy. AB - In generalized, non-convulsive, absence epilepsy, spike-and-wave discharges (SWD) are recorded in both the cortex and the thalamus. The effect of various cortical and thalamic lesions on the occurrence of spontaneous SWD was examined in rats from a strain with genetic absence epilepsy. Cortical ablations suppressed SWD recorded in the thalamus. KCl induced unilateral cortical spreading depression and transiently suppressed SWD in the ipsilateral cortex and thalamus; SWD recovered simultaneously in both structures. Bilateral thalamic lesions of the anterior nuclei, the ventromedial nuclei, the posterior area, or lesion of the midline nuclei did not suppress cortical SWD. However, large lesions of the lateral thalamus, including the specific relay and reticular nuclei, definitely suppressed ipsilateral SWD, and pentylenetetrazol, THIP or gammabutyrolactone failed to restore the cortical SWD. These results demonstrate that the neocortex and the specific thalamic nuclei are both necessarily involved in the generation of SWD in absence epilepsy. PMID- 1512596 TI - Role of the thalamic reticular nucleus in the generation of rhythmic thalamo cortical activities subserving spike and waves. AB - The role of the reticular thalamic nucleus (RTN) in pacing rhythmic cortical activities subserving spike-waves (SW) discharges has been investigated in rats. Intracellular recordings from thalamic slices in vitro demonstrated that RTN neurons from control animals possess a set of Ca2+/K+ membrane conductances which enable them to produce rhythmic oscillatory activities. In vivo, studies of Ca(2+)-conductance blockade by intrathalamic injections of Cd2+ were performed on 24 callosotomized Wistar rats displaying spontaneous SW discharges, bred at the Centre de Neurochimie, Strasbourg. A significant decrement in ipsilateral SW activity was consistently observed in all RTN-injected animals 40 min after Cd2+ injection. By contrast, animals which received Cd2+ injection into the ventroposterior complex (VP) showed only small changes in ipsilateral SW. It is concluded that Ca(2+)-dependent oscillatory properties of the RTN are critical for the expression of genetically determined SW discharges in the Wistar model. PMID- 1512597 TI - Responses to N-methyl-D-aspartate are enhanced in rats with petit mal-like seizures. AB - The responses to the glutamate agonist N-methyl-D-aspartate (NMDA) were studied in the sensori-motor cortex of rats with petit mal-like seizures. In a first study, the changes in extracellular concentration of calcium elicited through ionophoretic application of NMDA at various depths in the cortex were measured in vivo. The results show that in the cortex of epileptic rats the NMDA responses are much more widely distributed than in the cortex of control rats. In a second study, a current-source density analysis of the responses elicited through electrical stimulation of the white matter was performed in slices of neocortex in vitro. These findings show that the NMDA-dependent component of the synaptic responses are more widely distributed and of longer duration in the cortex of epileptic rats than in that of control rats. Taken together, these results suggest that in this model of absence epilepsy NMDA-dependent mechanisms are important in the triggering and maintenance of epileptic activity. PMID- 1512598 TI - Antitumor agents, 127. Bruceoside C, a new cytotoxic quassinoid glucoside, and related compounds from Brucea javanica. AB - Bruceoside C [5], a new quassinoid glucoside, and related compounds were isolated from Brucea javanica, and their structures were elucidated by spectral data. Bruceoside C showed potent cytotoxicities against KB, A-549, RPMI, and TE-671 tumor cells. PMID- 1512599 TI - Transformations of (+-)-salsolinol into optically active O- and/or N-methylated derivatives by several Papaveraceae plants and their tissue-cultured cells. AB - (+-)-Salsolinol [3], a substance possibly inducing parkinsonism, was biotransformed into optically active O- and/or N-methylated salsolinols 5, 6, and 7 by several Papaveraceae plants and tissue-culture cells derived from these plants. The bioconversion of racemic salsolinol into optically active tetrahydroisoquinolines has never been shown to occur, either in animals or in plants. PMID- 1512600 TI - A new triterpenoidal saponin from Acacia auriculiformis. AB - A new triterpenoidal saponin has been isolated from an aqueous EtOH extract of the legumes of Acacia auriculiformis and characterized as 3-O-([beta-D xylopyranosyl(1----3)-beta-D-xylopyranosyl(1----4)-alpha-L- rhamnopyranosyl(1--- 2)]-[alpha-L-rhamnopyranosyl(1----4)]-beta-D- glucopyranosyl)-3,16,21 trihydroxyolean-12-en-28-oic acid [1] by chemical studies and spectral data. PMID- 1512601 TI - An acetylated bidesmosidic saponin from Schefflera octophylla. AB - A new acetylated bidesmosidic triterpenoid saponin has been isolated from the leaves of Schefflera octophylla and structurally elucidated as 3-epi-betulinic acid 3-O-beta-D-6'-acetylglucopyranoside 28-[alpha-L-rhamnopyranosyl(1----4)-O beta-D-glucopyranosyl(1----6)]-bet a-D-0-glucopyranoside [1]. PMID- 1512602 TI - Brominated beta-carbolines from the marine tunicate Eudistoma album. AB - Chemical investigation of the cytotoxic EtOH extract of the marine tunicate Eudistoma album led to the isolation of three brominated beta-carbolines which were characterized by their spectral data. Two of them, eudistomin E, which is already known for its potent antiviral activity, and the novel compound eudistalbin A [1], were shown to possess cytotoxic activity (ED50 less than 5.0 ng and 3.2 micrograms/ml respectively) in vitro against the growth of KB human buccal carcinoma cells. The third compound, eudistalbin B [2], is a new inactive natural product. PMID- 1512603 TI - Neuroscience for clinicians. PMID- 1512604 TI - Second European Stroke Prevention Study. ESPS-2 Working Group. AB - The computerized design, aims, organization, and structure of the European Stroke Prevention Study 2 (ESPS-2) are presented. This clinical trial will investigate the effect of single and combination regimens of low-dose acetylsalicylic acid (50 mg daily) and dipyridamole (400 mg daily) versus placebo in secondary prevention of stroke and death. PMID- 1512605 TI - McLeod syndrome: a distinct form of neuroacanthocytosis. Report of two cases and literature review with emphasis on neuromuscular manifestations. AB - McLeod syndrome was originally described on the basis of a specific blood group phenotype with weak expression of Kell antigens. This erythrocyte abnormality also causes acanthocytosis. The haematological findings are associated with abnormalities in other organ systems, including neuromuscular manifestations. A 51-year-old patient was followed up for 11 years. He presented with persistent muscle creatine kinase elevation and progressive heart disease and later developed a slowly progressive neuropathy and choreic movements. His younger brother presented with grand mal seizures, involuntary movements and high muscle creatine kinase when aged 43 years. Clinical myopathy was absent in both, yet muscle biopsy showed mild myopathic changes. The presence of a motor axonopathy was supported by electrophysiological findings. One brother also showed sensory axonopathy. The movement disorder suggested accompanying basal ganglia dysfunction. Earlier reports of McLeod syndrome are reviewed with respect to neuromuscular involvement. Absence of the Kx membrane protein seems to be the cause of this multi-system disorder. PMID- 1512606 TI - Ataxic variant of adrenoleukodystrophy: MRI and CT findings. AB - A 28-year-old man developed slowly progressive dysarthria and gait disturbance over 7 years. Neurological examination revealed marked ataxia of articulation and gait, mild ataxia and spasticity of all four limbs without intellectual, visual, auditory, sensory or sphincter dysfunction. No physical signs of adrenal hypofunction were found. However, analysis of fatty acid of plasma sphingomyelin showed an increase in very long chain fatty acids, compatible with the diagnosis of adrenoleukodystrophy. Computed tomography disclosed marked atrophy of the cerebellum and pons, and bilateral low-density lesions in the deep while matter of the cerebellum. Magnetic resonance imaging showed these lesions more clearly, as well as other lesions in the middle and superior cerebellar peduncles, despite the absence of cerebral white matter involvement at the time of presentation. This is a rare case of adrenoleukodystrophy presenting as spinocerebellar degeneration and showing marked atrophy and several parenchymatous lesions of the cerebellum and brain stem. PMID- 1512607 TI - Specific antigen binding by activated cerebrospinal fluid B lymphocytes in acute neuroborreliosis. AB - A recently developed immunocytochemical antigen-binding sandwich test for the identification of specific activated B lymphocytes was applied to cerebrospinal fluid cells and peripheral blood mononuclear cells in patients with acute neuroborreliosis. Discrimination of antigen-binding phagocytes was achieved by double staining with monoclonal antibodies. Specific activated B lymphocytes were much more numerous in cerebrospinal fluid than in blood, showing great interindividual differences. When intrathecal immunoglobulin production was present, the number of specific activated B lymphocytes was also high. The specificity of all activated B lymphocytes ranged from 10% to 60% and was higher in the acute stage than after treatment. PMID- 1512608 TI - Extracranial vertebral artery dissection: nine cases. AB - Nine patients (six men, three women) with extracranial vertebral artery dissection are described. Their mean age was 39.1 years (range 17-66). In four cases dissection was "spontaneous"; in the other five cases there was a history of trivial trauma. Three patients had fibromuscular dysplasia, two were migraineurs, one had elastorrhexis. Treatment varied. Six received heparin, three acetylsalicylic acid or ticlopidine. Eight had good recovery. Two patients experienced recurrence when stopping acetylsalicylic acid. The pathogenesis of dissections and the distinction between spontaneous dissections and those associated with minor trauma are discussed. PMID- 1512609 TI - Thalamic ataxia. AB - Seventeen patients with hemiataxia as a manifestation of thalamic infarction were studied. Hemiataxia had the main clinical characteristics of a "cerebellar type" of ataxia, though it never occurred in isolation, being associated with ipsilateral sensory disturbance (hemiataxia-hypaesthesia) in 7 patients, with ipsilateral sensory disturbance and hemiparesis (hypaesthetic ataxic hemiparesis) in 8 patients, and with hemiparesis (ataxic hemiparesis) in 2 patients. Recovery was good, and in all patients the sensory and motor disturbances improved or cleared before the hemiataxia. All patients had an infarct involving the lateral part of the thalamus (thalamogeniculate territory in 16, tuberothalamic territory in 1), also affecting the posterior limb of the internal capsule (PLIC) in 7 patients. Hemiataxia seemed linked to involvement of the caudal part of the ventral lateral nucleus of the thalamus or the immediately adjacent medial part of the PLIC. These structures are near the corticospinal pathways and the ventral posterior nucleus of the thalamus, explaining why hemiataxia is associated with hemiparesis or hypaesthesia in this type of infarct. PMID- 1512610 TI - Multimodal tests of cerebrovascular reactivity in migraine: a transcranial Doppler study. AB - Altered cerebral vasoreactivity (CVR) has been implicated in migraine. To test this hypothesis, we studied CVR as measured by transcranial Doppler ultrasound (TCD) in 11 migraineurs and 12 healthy controls of similar age. Mean flow velocities (MFV) in the middle cerebral artery (MCA) were recorded during a cognitive and two motor tasks. MFV in the posterior cerebral artery (PCA) were measured during photic stimulation and observation of complex images. The increase of MFV in the MCA during the cognitive task was greater in migraineurs than in controls (9.1% vs 5.0%; P = 0.06). The increase of MFV in both tests for PCA reactivity was significantly greater in migraineurs than in controls: 17.4% vs 9.9% for photic stimulation (P less than 0.05) and 20.3% vs 10.2% for observation of complex images (P less than 0.05). Owing to overlap of individual results, the discriminative value of both tests was unsatisfactory. The variability of flow velocities as measured by standard deviations of MFV was significantly greater in migraineurs than in controls during all tests of PCA vasoreactivity. Differences in CVR between migraineurs and normal controls may be detected by TCD testing, in particular in the PCA territory. For individual diagnostic purposes, CVR tests proved to be insufficient. PMID- 1512611 TI - Familial CNS tumors. AB - A family with central nervous system tumors in five individuals in two generations is reported. Of five sisters, two had an isolated meningioma and one an ependymoma. Amongst the four children of those affected there was a son with two cerebral meningiomas and a daughter with a spinal meningioma. Signs typical of von Recklinghausen neurofibromatosis (NF1) or bilateral acoustic neurofibromatosis (NF2) were not present. The pattern is consistent with autosomal dominant inheritance with relatively high penetrance. PMID- 1512612 TI - Langerhans' cell histiocytosis and the nervous system. AB - We report two cases of Langerhans' cell histiocytosis with unusual central nervous system (CNS) involvement. The first patient had behavioural disturbances, memory loss and diabetes insipidus. His response to a range of treatments was poor. The second patient presented with seizures and headaches suggestive of raised intracranial pressure. Etoposide (VP16) chemotherapy led to a dramatic clinical and radiological improvement. The various CNS manifestations of Langerhans' cell histiocytosis and their management are discussed. PMID- 1512613 TI - Prevalence of hereditary ataxias and spastic paraplegias in Molise, a region of Italy. AB - An epidemiological survey of hereditary ataxias and paraplegias was conducted in Molise, a region of Italy (335, 211 inhabitants on 1 January 1989). Total prevalence was 7.5 x 10(-5) inhabitants (95% confidence limits 4.8-11.1). There were 7 patients with Friedreich's disease, 5 with early onset cerebellar ataxia with retained tendon reflexes, 4 with ataxia-telangiectasia, 9 with hereditary spastic paraplegias (2 autosomal dominant and 7 autosomal recessive cases). There was no patient with autosomal dominant cerebellar ataxia. PMID- 1512614 TI - Is CNS involvement in acute and chronic neuroborreliosis HLA-related? PMID- 1512615 TI - Recovery from respiratory muscle failure in a sporadic case of Brown-Vialetto-Van Laere syndrome with unusually late onset. PMID- 1512616 TI - Stroke in an HIV-infected patient. PMID- 1512617 TI - Bereavement experiences: caring for a partner with AIDS. PMID- 1512618 TI - HIV disease and levels of prevention. AB - It appears that several cofactors are involved in determining the pathogenesis of HIV disease. Exposure cofactors affect acquisition of HIV infection. Trigger cofactors determine a person's likelihood of being infected after exposure to HIV, or contribute to HIV disease progression in those who have been infected. Identification of the most common exposure and trigger cofactors should become a major focus of community health nursing practice at all levels of prevention. Changes in behaviors, early intervention activities, and rehabilitative measures related to known cofactors may improve the health of persons at all stages of HIV disease. PMID- 1512619 TI - A collaborative effort between a state migrant health program and a baccalaureate nursing program. AB - This article reports on the way in which a unique collaborative effort between a service agency and a baccalaureate nursing program grew out of the needs of the two separate agencies. The first agency, the Colorado Migrant Health Program, was faced with a budget that was inadequate to meet the health-care needs of the migrant population. The second, a baccalaureate nursing program at the University of Colorado, was finding it increasingly difficult to locate appropriate generalized community health clinical placements with an opportunity for student discovery learning related to transcultural health care. Discussions of a collaborative effort ensued and it became evident that each had something to gain from such an effort. Now, after almost 10 years of cooperation, the commitment to the endeavor on the part of both agencies remains strong as the benefits to each continue to increase. The ultimate beneficiaries, however, are the migrant families receiving care and the students providing care. The way in which the program has evolved over time, a description of the current program, and a discussion of the resources that help to maintain the program are presented. In addition, the curriculum course design, and teaching strategy modifications necessary to facilitate the collaborative program are discussed. PMID- 1512620 TI - Cultural impact of health-care access: challenges for improving the health of African Americans. AB - Disparities in health status of African Americans continue to exist. These disparities of poor health, in part, are attributed to decreased access to health care services. However, culture plays a key role in health-care utilization patterns among African Americans. The purpose of this article is to examine cultural factors that affect health-care practices among African Americans and to identify specific community health nursing interventions that integrate these factors into health-care plans for African-American families and communities. PMID- 1512621 TI - Predictors of the home environment of high-risk infants. AB - The quality of the home environment is an important predictor of the cognitive and social development of high-risk infants. Community health nurses (CHNs) have played a central role in the assessment and care of families with high-risk infants. We examined predictors of the home environment in a sample of 106 infants discharged from a neonatal intensive care unit. The most consistent predictor of an optimal home environment was an internal parental locus of control. Socioeconomic status affected dimensions of parenting related to cognitive stimulation but not emotional responsivity. Young mothers and those with other children are less responsive to their infants. Males are treated in a more responsive manner than females. These findings suggest that CHNs need to adopt an empowerment model of intervention and focus on the particular needs of young mothers and those with other children. PMID- 1512622 TI - Intervention program for obese school children. AB - The purpose of this study was to implement and evaluate a program for obese school children. A pretest-posttest design was utilized. Data was collected related to weight status, skinfold measurements, self-esteem, and nutritional knowledge. A convenience sample of 26 children, in the fourth to sixth grades, completed this 9-week program. The results indicate that self-esteem increased significantly (p less than .001) between the pretest and posttest interval. Weight status and nutritional knowledge showed no improvement. Exercise was difficult to assess on self-report, therefore no conclusions were were drawn in relation to this variable. Future research will be directed toward refining this intervention program. PMID- 1512623 TI - OSHA final hepatitis and HIV exposure standard. PMID- 1512624 TI - Nutrient intake as a time signal for circadian rhythm. AB - In considering nutrition and circadian rhythms, time-of-eating behavior is an inherited, genetically controlled pattern that can be phase-shifted by conditioning or training. In addition, there are metabolic responses to meal eating, such as entrainment of a number of enzyme levels, hormone concentrations and other metabolic and physiologic activities. To separate truly inherent rhythms from entrained responses, it is necessary to determine which oscillations continue their circadian rhythms under completely free-running conditions of no zeitgeber, such as darkness vs. light or meal eating vs. fasting. Where meal eating provides a time signal to a biological clock experiment, healthy animals not starving but constantly receiving nutrition to avoid an eating time signal should be used. The ability to determine which daily rhythms are not genetically inherent, but rather are responses to a particular time signal, requires the elimination of all but this time signal. By using free-running conditions that are totally without time-giving signals, entrainment by (response to) meal feeding is readily separated from inherited endogenous circadian rhythm. Both types of daily rhythm exist and both involve the biological clock mechanisms . A method by which to identify each is proposed. PMID- 1512625 TI - Postnatal selenium repletion protects lungs of neonatal rats from hyperoxia. AB - We reported previously that Se-adequate neonatal rat pups born to Se-adequate dams were resistant to lung damage by hyperoxia. To assess whether early postnatal Se repletion could also protect developing pups reared under hyperoxia, female Sprague-Dawley rats (n = 20) were bred and fed a Se-deficient (0.04 microgram/g) diet during pregnancy. On d 1 postpartum, dams were divided into two groups and fed either a Se-deficient diet or a Se-repleted (0.5 microgram/g) diet. On d 4 postpartum, litters in each group were randomly assigned to either air or high oxygen (greater than 95% O2) environments. Histologic evaluation of lungs from d-8 pups indicated that Se repletion significantly reduced the incidence of lung lesions caused by hyperoxia. Selenium-repleted pups also had significantly greater lung volumes and internal surface areas. The 7-d period of Se repletion resulted in significantly elevated maternal milk Se concentrations compared with a Se-deficient group, which was reflected in the pups by elevated plasma and hepatic Se concentrations and Se-dependent glutathione peroxidase (SeGPx) activities. Pulmonary glutathione concentration and SeGPx activity in pups were affected by oxygen exposure only, not by Se nutrition. Therefore, early postnatal Se repletion can protect the developing lung from oxygen-induced injury, a protection that is not entirely due to the effects of Se on pulmonary SeGPx activity and glutathione concentration. PMID- 1512626 TI - Dietary beta-carotene reduces serum lipid concentrations in spontaneously hypertensive rats fed a vitamin A-fortified and cholesterol-enriched diet. AB - The effects of dietary beta-carotene on serum lipid concentrations were examined in spontaneously hypertensive (SH) rats. Groups of SH rats were fed a semipurified, vitamin A-fortified and cholesterol-enriched diet supplemented with 0, 125, 250 or 500 mg beta-carotene/kg diet for a period of 44 d. beta-Carotene supplementation resulted in significant dose-related decreases in serum total, LDL and HDL cholesterol concentrations and serum total, VLDL and LDL triacylglycerol concentrations. The ratio of HDL cholesterol to total cholesterol was unchanged or slightly increased by dietary beta-carotene. The study suggests that dietary beta-carotene has antihyperlipidemic effects in SH rats. The effects in humans and the mechanism of the effects remain to be investigated. PMID- 1512627 TI - Tryptophan intake influences infants' sleep latency. AB - Formula-fed infants have depressed plasma tryptophan concentration relative to human milk-fed infants. Because tryptophan alters sleep-waking patterns in adults, a study was designed to determine whether additional dietary tryptophan could elevate plasma tryptophan concentrations of formula-fed infants to concentrations characteristic of human milk feeding and whether differences in plasma tryptophan or the ratio of plama tryptophan to the sum of the other plasma large neutral amino acids (tryptophan:LNAA) were of behavioral significance. Infants were fed a formula (13 g protein/L; whey:casein, 34:66) containing either 0, 294, 588 or 882 mumol/L of added tryptophan. Infants fed human milk or commercial formula (15 g protein/L; whey:casein, 18:82) were included for comparison. In formula-fed groups, plasma tryptophan was directly related to tryptophan intake (r = 0.46, P less than 0.0005). Infants fed commercial formula or the formula without added tryptophan had lower (P less than 0.001) plasma tryptophan compared with infants fed human milk. Only the infants fed the highest tryptophan formula had significantly higher plasma tryptophan:LNAA ratios than the other experimental groups, and these ratios were similar to those of infants fed human milk. The plasma tryptophan:LNAA ratios, not plasma tryptophan concentrations, were predictive of differences in the infants' sleep latency; infants fed formula containing the highest tryptophan had sleep latencies of 18.7 min, significantly shorter (P less than 0.05) than those of infants fed formulas containing less added tryptophan (27.7 min). Feeding infants formulas differing in tryptophan concentration produced differences in sleep latency, which could influence neurobehavioral developments.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1512629 TI - Adipocyte insulin responsiveness in female Sprague-Dawley rats fed a low fat diet containing a fat-mimetic carbohydrate. AB - Two experiments examined the effects of replacing high fat with low fat diets on adipocyte insulin sensitivity and response. Female Sprague-Dawley rats had free access to diets containing 21% (control), 61% (high fat) or 2% (low fat) of energy as fat. In the low fat diet a carbohydrate-based fat-mimetic carbohydrate replaced all but the essential fat present in the high fat diet. Insulin stimulated glucose utilization by isolated adipocytes was measured after 10, 30 or 50 d. In a second study adipocyte insulin saturation curves were measured after 36 d. Rats fed the high fat diet for 30 d were insulin resistant and adipocyte basal and insulin-stimulated glucose utilization were depressed. The low fat diet initially stimulated glucose utilization of adipocytes but did not change insulin responsiveness. After 50 d there was no difference in glucose utilization between adipocytes from rats fed control and low fat diets. Insulin resistance in rats fed the high fat diet was associated with a nonsignificant reduction in insulin receptor number. These observations do not exclude the possibility of a post-receptor defect in glucose utilization. PMID- 1512628 TI - Correlations of vitamin A and E intakes with the plasma concentrations of carotenoids and tocopherols among American men and women. AB - The authors investigated the association of diet and other factors with the plasma concentrations of carotenoids, retinol and tocopherols in a sample of 121 men and 186 women participating in two prospective investigations of dietary etiologies of chronic diseases. Lycopene (mean concentration, 0.82 mumol/L in men, 0.76 mumol/L in women), beta-carotene (mean 0.46 mumol/L in men, 0.58 mumol/L in women) and lutein (mean 0.28 mumol/L in men, 0.27 mumol/L in women) were the major circulating carotenoids. Among nonsmokers, dietary carotenoid, as typically calculated in epidemiologic studies, was significantly correlated with plasma beta-carotene (r = 0.34 in men, r = 0.30 in women), alpha-carotene (r = 0.52 in men, r = 0.37 in women) and lutein (r = 0.36 in men, r = 0.19 in women), but not with plasma zeaxanthin (r = 0.11 and r = 0.02) or lycopene (r = 0.13 and r = 0.01) after adjusting for plasma cholesterol and triglycerides, body mass index and energy intake. Total vitamin E intake was positively associated with plasma concentrations of alpha-tocopherol (r = 0.51 in men, r = 0.41 in women) and inversely associated with plasma concentrations of gamma-tocopherol (r = 0.51 in men r = -0.42 in women), but this was primarily due to use of vitamin E supplements. Measurements of specific carotenoids can provide independent information beyond the usual calculation of carotene intake in epidemiologic studies. PMID- 1512630 TI - Insulin insensitivity is rapidly reversed in rats by reducing dietary fat from 40 to 30% of energy. AB - The objective of this study was to determine the effect of reducing dietary fat content from 40 to 30% of total energy on body composition and insulin sensitivity in rats. Female Sprague-Dawley rats were fed either a control diet (30% energy as fat) or a high fat diet (40% energy as fat) for 10 wk. In vivo glucose tolerance tests indicated that both basal and glucose-stimulated insulin concentrations were elevated in rats fed the high fat diet. Two groups of rats offered the high fat diet were then fed the control diet (HF,C) and two that had received the high fat diet were then fed a diet (30% energy as fat) containing a fat-mimetic carbohydrate (HF,M). Two groups continued to receive the high fat diet and two groups continued to receive the control diet. Rats were killed 1 and 2 wk after the diet switch. In vivo glucose tolerance tests indicated that insulin sensitivity was corrected in HF,C and HF,M rats after 3 d. Body fat content was greater in rats fed the high fat diet and remained high after 7 d of consuming either diet with 30% of energy from fat. There was no effect of diet on liver fatty acid utilization or on diaphragm glucose oxidation. Adipocytes from all treatment groups were insulin resistant, possibly due to feeding status or age of the rats. The results of this study suggest that a moderate reduction in fat intake, from 40 to 30% of energy, can produce a rapid improvement of insulin sensitivity in insulin-insensitive rats, independent of changes in body fat content and irrespective of the means used to reduce dietary fat content. PMID- 1512631 TI - Total parenteral nutrition with short- and long-chain triglycerides: triacetin improves nitrogen balance in rats. AB - Little is known about the long-term metabolic effects of parenteral administration of short-chain triglycerides. These studies were undertaken to investigate triacetin, the water-soluble triglyceride of acetate when it is incorporated into nutritionally balanced total parenteral nutrition formulas. Male Sprague-Dawley rats (n = 22) were fed an isovolemic, isocaloric and isonitrogenous diet for 7 d. The lipid energy represented 30% of the nonprotein energy with short-chain triglycerides representing 0, 50 or 90% of the lipid energy. Plasma acetate concentration was determined as well as indicators of protein metabolism: daily and cumulative nitrogen balance, whole body leucine kinetics and rectus muscle and liver fractional protein synthetic rates. No overt toxic effects were observed at any point during the study. As the proportion of short-chain triglycerides in the diet increased from 0 to 50 or 90% of the lipid energy, cumulative nitrogen balance increased 50 or 120%, respectively (P less than 0.05). Whole-body and tissue leucine kinetics (determined during the last 2.5 h of the 7-d study) were unaffected by the lipid composition of the diet. Plasma acetate concentration was not significantly different among groups. These results indicate that incorporation of the short-chain triglyceride, triacetin, in nutritionally balanced total parenteral nutrition formulas improves nitrogen balance with no overt toxic effects. These data indicate that triacetin may have a future role as a parenteral nutrient, and that further studies of its use are warranted. PMID- 1512632 TI - Neonatal genetically lean and obese pigs respond differently to dietary cholesterol. AB - The impact of cholesterol exposure in early life on later cholesterol metabolism is not clearly understood. Sixteen newborn genetically lean and obese pigs were fed 0 or 5.0 g cholesterol/kg diet (0 or 0.5%) (liquid diets for 12 d, dry diets thereafter) for 33 d, after which they were all fed 10.0 g cholesterol/kg diet (1.0%) for 23 d. All animals were killed on d 56 and whole-body protein, fat and water were determined on the ground carcass. Dietary cholesterol had no consistent effect on growth rates or body composition. Mean fat content of lean pigs was 15.1% compared with 22.7% for obese pigs; corresponding values were 14.8 and 14.4% for protein and 65.5 and 58.3% for water. Concentrations of plasma total cholesterol, HDL cholesterol and apolipoproteins B and A-1 were increased by 0.5% dietary cholesterol in obese but not in lean piglets, although dietary cholesterol caused HDL and LDL size distribution profiles to shift toward larger sized components in both strains. Plasma total cholesterol and apolipoprotein B concentrations rose two- to eightfold in all groups after the 1% cholesterol diet was consumed; these changes were accompanied by shifts in LDL and HDL size distribution profiles towards larger-sized components. With 1.0% cholesterol in the diet of all groups, HDL cholesterol concentration increased by approximately 50% in both groups of lean pigs and in obese pigs previously fed cholesterol, but did not increase further in obese pigs previously fed 0.5% cholesterol. The magnitude of the hypercholesterolemic response in lean pigs was blunted by previous exposure to 0.5% dietary cholesterol, but the response was accentuated in obese animals that had been previously exposed to 0.5% dietary cholesterol. These data provide evidence that genetic differences between obese and lean pigs affect their serum lipoprotein responses to high cholesterol intake. PMID- 1512633 TI - Modification of triacylglycerides and apolipoprotein B in rats fed diets containing whole milk, skim milk and milk proteins. AB - The objective of this study was to determine the effects of diets containing milk and milk protein fractions on plasma and hepatic lipids, apolipoprotein B mRNA abundance, and plasma apolipoprotein concentrations and lipoprotein composition. Male rats were fed for 6 wk diets that contained (wt/wt) 76% whole milk (WM diet), 55% skim milk (SMFF diet), 22% casein (CAS diet), 22% whey protein isolate (WHY diet) or 55% skim milk-low fat (SMLF diet). The fat concentration in the SMLF diet was 7%. Butter oil (20%) and corn oil (2%) were added to the SMFF, CAS and WHY diets. Plasma and VLDL triacylglycerides in the WM-fed rats were about half of the level in the groups fed the SMFF and SMLF diets, but not significantly different from those of the WHY-fed group. Hepatic triacylglycerides generally were lower in the WM-fed group than in the other groups. Plasma cholesterol concentration did not differ among groups. Plasma apolipoprotein B was significantly lower in the WM-fed group than in rats fed the SMLF, SMFF or WHY diets. However, apolipoprotein B mRNA abundance in the liver and small intestinal mucosa did not differ due to dietary treatment. Thus the lipemic response due to whole milk is not associated with milk protein fractions and may be due to the presence of fat globule membrane in the diet containing whole milk. PMID- 1512634 TI - Folic acid, 5-methyl-tetrahydrofolate and 5-formyl-tetrahydrofolate exhibit equivalent intestinal absorption, metabolism and in vivo kinetics in rats. AB - The intestinal absorption and in vivo kinetics of (6S)-[3H]-5-methyl tetrahydrofolate (5-methyl-H4folate), (6S)-[3H]-5-formyl-H4folate and [3H]folic acid were investigated to determine whether inherent differences exist in the overall bioavailability of these folates in rats. Adult rats (n = 9 per group) were given an intragastric dose of the appropriate folate (50 pmol/100 g body wt) in 50 mmol/L ascorbate (pH 7). Each compound underwent nearly complete absorption within 8 h, and there was no significant difference in the excretion kinetics in relation to the form of folate administered. A biphasic pattern of excretion was observed over the following 8 d. Both urine and feces were important excretory routes. The rapid phase of total isotopic excretion (urinary and fecal) exhibited a half time (t1/2) of 0.11-0.12 d, whereas the t1/2 of the slower phase was 13.4 15.9 d. Isotopic distributions and the pattern of labeled folates in urine and tissues were similar regardless of the form administered. These results indicate that the bioavailability of orally administered folic acid, 5-methyl-H4folate and 5-formyl-H4folate is equivalent in rats under the conditions of this study. PMID- 1512635 TI - Modification of plasma and hepatic lipids of guinea pigs by feeding high oleic acid pork compared with regular pork. AB - Meat from such monogastric animals as swine can be modified to substitute monounsaturated fatty acids for saturated fatty acids. Because monounsaturated fatty acids have a beneficial effect on serum lipids as compared with saturated fatty acids, the objective of this study was to assess the effect of modified pork as compared with regular pork on serum and hepatic lipids. Guinea pigs were fed diets containing pork from control diet-fed hogs or from hogs fed a diet containing high oleic acid sunflower oil. The pork provided almost all of the fat in the diets at the level of 4 and 15 g/100 g diet, 10 or 34% energy. The high oleic pork muscle and fat contained 26 and 46% less palmitic and stearic acids (the primary saturated fatty acids), respectively, and 31 and 29% more oleic acid (the primary monounsaturated fatty acid) than the regular pork muscle and fat, respectively. Cholesterol concentration of diets ranged from 0.06 to 0.08% of the diet. Although total serum cholesterol, HDL cholesterol and triglyceride concentrations did not differ due to type of pork, results indicated that serum LDL cholesterol was lower (15%) and hepatic cholesterol was greater (15%) in the high oleic pork, 15% fat group as compared with the control pork 15% fat group. Also, serum LDL cholesterol concentration was higher in the groups fed 15% fat compared with those fed 4% fat. In this study pork modified to have more oleic acid and less saturated fatty acids had a positive effect on tissue lipids when fed to animals. PMID- 1512636 TI - Efficiency of dietary methionine utilization by young pigs. AB - An assay was conducted to determine the efficiency of dietary methionine retention for protein accretion in 14-kg pigs. During an 18-d feeding period, pigs were fed a chemically defined amino acid basal diet [147.7 g protein (N x 6.25)/kg, 14.43 MJ metabolizable energy/kg, 4000 mg L-cystine/kg] containing 1150, 1725 or 2300 mg L-methionine/kg. Linear (P less than 0.01) responses in daily gain, daily food intake, daily methionine intake, gain:food ratio and empty body weight gain were obtained as dietary methionine level increased. Representative pigs were killed at the beginning of the assay for whole-body compositional analysis, and the comparative slaughter technique was used to estimate methionine retention. Absolute retention of methionine, protein, water, fat and ash increased linearly (P less than 0.05) with dietary methionine supplementation. Regressing methionine retained on methionine intake resulted in an efficiency of methionine retention above maintenance of 71.7%. The maintenance requirement for methionine was estimated to be 57 mg/d (8 mg/kg body wt 0.75) in the presence of excess dietary cystine. Concentrations of most indispensable amino acids, including methionine, in whole-body protein increased linearly, although glycine and proline concentrations decreased as dietary methionine level increased. This suggests that the ratio of whole-body collagen protein to non collagen protein decreases as dietary methionine is incremented from deficiency to near adequacy. PMID- 1512637 TI - Rat serum osteocalcin concentration is determined by food intake and not by inflammation. AB - Osteocalcin, or bone gla protein, is the major noncollagenous protein in bone. Previous findings of decreased serum osteocalcin concentrations in children with Kwashiorkor led us to analyze the respective influence of nutritional status and inflammation on circulating osteocalcin in growing rats. Food deprivation for 72 h induced a significant 24% decrease in serum osteocalcin. Refeeding produced a rapid rise in serum osteocalcin, which reached control concentrations after 24 h of refeeding. Bone osteocalcin was not affected by these dietary manipulations. The changes in serum osteocalcin were not correlated with serum 1,25 dihydroxycholecalciferol, whereas they could be related to serum 25 hydroxycholecalciferol concentrations. Turpentine injection reduced serum osteocalcin concentration, but pair-feeding showed that this decrease was entirely attributable to spontaneous food restriction and not to inflammation. By contrast, the sensitive nutritional marker, serum transthyretin, was affected by both inflammation and food restriction. These results indicate that serum osteocalcin is closely related to food intake but not to inflammation, suggesting that the dramatic decrease in serum osteocalcin that we previously observed in children with Kwashiorkor is due to malnutrition per se. PMID- 1512638 TI - Consumption of milk from cows immunized with intestinal bacteria influences age related changes in immune competence in mice. AB - Milk was obtained from nonimmunized cows and cows immunized with a mixture of various human gut bacteria. Each milk was administered orally to 2-mo-old C57BL/6 mice at a dose of 150 g.kg-1.d-1 for either 6 or 16 mo. The study group had fewer enteric bacteria and a lower concentration of the serum antibodies against enteric bacteria compared with the control group at 8 and 18 mo of age. Furthermore, the study group at 18 mo old had a higher redirected cytotoxicity of intestinal intraepithelial lymphocytes, a higher proliferative response of mesenteric lymph nodes cells against mitogenic or alloantigenic stimulation and a greater ability of the spleen cells to produce anti-sheep erythrocytes IgG antibody after systemic immunization with sheep erythrocytes. A lower level of autoantibodies was observed at 8 mo and 18 mo of age in the study group compared with the control group. These results suggest that the senescence of the murine immune system may be delayed by consumption of milk from immunized cows. PMID- 1512639 TI - Bioavailability of vitamin B-6 in pregnant rats. AB - The cause for reduced plasma pyridoxal phosphate (PLP) concentration during pregnancy is not well understood. In this study, nonpregnant (control) and pregnant rats were gavaged with [3H]pyridoxine for assessment of the intestinal absorption, tissue distribution, metabolic utilization and urinary excretion of the vitamin. In addition, plasma PLP and pyridoxal levels and erythrocyte aspartate aminotransferase (EAST) activity were measured. There was 50% lower plasma PLP concentration and 50% greater EAST activity in the pregnant rats and no difference in the stimulation of EAST with exogenous PLP. There was no difference in the intestinal absorption, hepatic uptake and retention or urinary excretion of the radioisotope. Less than 3% of the oral dose was detected in fetal/uterine tissue of the pregnant rats. Results of this study indicate that reduced plasma PLP concentration during pregnancy is not a result of diminished total vitamin B-6 body pools or fetal sequestration of vitamin B-6. Low plasma PLP during pregnancy may be a result of altered distribution of PLP between the plasma and erythrocytes. PMID- 1512640 TI - Beta-carotene, retinol and retinyl ester concentrations in serum and selected tissues of ferrets fed beta-carotene. AB - The concentrations of beta-carotene, retinol and retinyl esters in serum and selected tissues of ferrets fed diets supplemented with beta-carotene (80 micrograms/g wet diet) for 3 wk were determined. The initial concentration of serum beta-carotene was 0.011 +/- 0.006 mumol/L (mean +/- SEM); at the end of the experimental period it was 5.75 +/- 1.60 mumol/L. No significant differences in serum retinol and total retinyl esters were observed between beta-carotene-fed and control ferrets that had been fed an unsupplemented diet. The predominant retinyl esters in serum were retinyl stearate (53%) and retinyl palmitate (35%). Of the tissues analyzed after beta-carotene feeding, the liver contained the highest concentration of beta-carotene (78.8 +/- 18.8 nmol/g). Other tissues that contained beta-carotene in amounts ranging from 17 to 20 nmol/g were adrenals, small intestine, stomach and colon; lesser amounts (6.9 nmol/g) were found in kidneys. Amounts ranging from 1.2 to 2.3 nmol/g were found in muscle, bladder, adipose tissue, lungs and skin; only 0.37 and 0.34 nmol/g were present in brain and eyes, respectively. Thus, like humans, ferrets have the capacity to absorb intact beta-carotene and to store this compound in tissues, especially the liver. However, compared with humans, ferrets have elevated concentrations of retinyl esters in serum, liver and other tissues. PMID- 1512641 TI - Dietary ascorbic acid depresses plasma and low density lipoprotein lipid peroxidation in genetically scorbutic rats. AB - The effects of dietary ascorbic acid on plasma lipoprotein and liver lipid peroxide concentrations were examined using ODS od/od rats with a genetic defect in the ability to synthesize ascorbic acid. ODS od/od rats were fed purified diets supplemented with 0 to 300 mg ascorbic acid/kg diet for 21 d. An ascorbic acid-free diet induced body weight loss, depleted ascorbic acid in the plasma and increased thiobarbituric acid-reactive substances in the plasma and liver as compared with rats fed ascorbic acid supplemented diets and with normal ODS +/+ rats fed the ascorbic acid-free diet. Increasing ascorbic acid concentration in the diet inhibited the development of these ascorbic acid deficiency symptoms in a dose-dependent manner. The dietary requirement of ascorbic acid to maintain normal body weight gain and plasma lipid peroxide concentrations was approximately 150 mg ascorbic acid/kg diet. On the other hand, even 300 mg ascorbic acid/kg diet was insufficient to maintain a hepatic concentration of ascorbic acid comparable to that in the liver of ODS +/+ rats. The lipid peroxide concentration in plasma LDL and liver was significantly elevated in ODS od/od rats fed the ascorbic acid-free diet. Supplementing the diet with 300 mg ascorbic acid/kg kept those concentrations within the normal ranges seen in the ODS +/+ rats. PMID- 1512643 TI - Does food restriction retard aging by reducing metabolic rate? PMID- 1512642 TI - Inhibitory effect of soybean protein vs. casein on apparent absorption of magnesium in rats is due to greater excretion of endogenous magnesium. AB - Apparent magnesium absorption is depressed in rats fed diets containing soybean protein or enriched with sodium phytate or phosphate in comparison with casein, whereas it is raised in rats fed lactose. However, the possibility that changes in apparent absorption are caused by changes in fecal excretion of endogenous magnesium cannot be excluded. We studied the effects of casein, soybean protein, sodium phytate, lactose and phosphate on apparent and true absorption of magnesium. True magnesium absorption was measured with the use of oral and intraperitoneal administration of tracer doses of 28Mg. Fecal excretion of endogenous magnesium was calculated from apparent and true absorption. True magnesium absorption was not affected by either substitution of soybean protein for casein or by the addition of sodium phytate to a diet containing casein. Endogenous magnesium excretion in feces was significantly increased by soybean protein and sodium phytate. Thus the observed impairment of apparent magnesium absorption in rats fed soybean protein or sodium phytate is due to enhanced fecal excretion of endogenous magnesium. With the other dietary treatments, enhanced fecal excretion of endogenous magnesium was not associated with a discrepancy in the effects on apparent and true magnesium absorption. Dietary lactose vs. dextrose and supplemental phosphate both stimulated fecal excretion of endogenous magnesium, but lactose raised both true and apparent magnesium absorption, and phosphate depressed both true and apparent magnesium absorption. PMID- 1512644 TI - Annotated guidelines on gifts to physicians from industry. American Medical Association Council on Ethical and Judicial Affairs. AB - We have responded on an individual basis to many requests for interpretations of grey areas in the opinion on gifts from industry since its release in December 1990, and many physicians and companies asked for a detailed list of these interpretations. While the council agrees with the concerns several individuals have expressed about additional rules, it authorized this revised list of questions and answers which replaces the earlier draft. It also established three main principles for future implementation: 1. The key principles of the guidelines should be carefully observed by physicians, and the AMA will remain active in attempting to secure compliance by its members. The overriding rule is that individual physicians should not accept substantial gifts from industry, even if the gift has an educational or patient benefit. It is important that the profession set clear and enforceable standards in this regard. 2. Professional associations should make their own interpretations of the appropriateness of gifts to them from industry. Under appropriate conditions, associations of physicians may, of course, receive gifts from industry. 3. Neither the council nor its staff will attempt to regulate minor issues or minute details of compliance. For many situations there are no yes or no answers. Some black letter rules are necessary so that conduct that should be changed is changed. In addition, they aid companies which want to comply with the spirit as well as the letter of the guidelines without putting themselves at a competitive disadvantage. The six points of the Opinion cover most situations and compliance to date has been good.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1512645 TI - The state of adult day care in Oklahoma. AB - Adult daycare is a concept whose time has come, according to the author. And the facts seem to bear him out. PMID- 1512646 TI - Birth weight-specific fetal deaths and neonatal mortality and the rising cesarean section rate. AB - To address the question of what effect the rising cesarean section rate has on fetal and neonatal mortality, 33,843 births and 4,132 sections were studied at a community hospital (1968-1987). Crude fetal and neonatal mortality rates declined as the annual section rate rose from 4.7% to 25.7%. However, weight-specific mortality rates bore little relationship to weight-specific section rates. Neonatal mortality rates for infants weighing over 2499 g and without congenital anomalies remained essentially the same (.91, 1.0, 1.02 per 1000 live births) for each of the five-year periods included in the study, despite marked increases in section rates. Among fetal deaths in this weight group, only antepartum deaths declined in each period. This analysis of birth weight-specific mortality indicates that a five-fold rise in the annual cesarean section rate has contributed little, if anything, to reductions in fetal and neonatal mortality during this time. PMID- 1512647 TI - Writer expresses yet another view on February AIDS commentary. PMID- 1512648 TI - New diarrhea treatment coming? PMID- 1512649 TI - [Ventilation and passages in the middle ear. A study by HRCT in patients with attic cholesteatoma]. AB - Operative records of 75 patients with acquired attic cholesteatoma were evaluated and compared with preoperative HRCT findings. The cholesteatoma extensions were classified into five groups as follows; Group 1 (cholesteatoma limited to the attic, 9 cases), Group 2 (cholesteatoma occupying both the attic and the aditus, 5 cases), Group 3 (cholesteatoma extending down to the posterior tympanum, also occupying an area as in Group 2, 6 cases), Group 4 (cholesteatoma occupying the attic, the aditus and the mastoid antrum, 14 cases), and Group 5 (cholesteatoma extending down to the posterior tympanum, also occupying an area as in Group 4, 41 cases). Ventilatory conditions, or the existence of soft tissue density, were evaluated by HRCT at such locations as the supratubal recess, mesotympanum, anterior and posterior parts of the tympanic isthmus, epitympanum, and mastoid antrum. Results are as follows. In Group 1, all these locations were aerated with the exception of a few cases. In Group 2, complete opacification was observed in almost all of the antrums. Soft tissue masses involved the anterior and/or posterior parts of the tympanic isthmus in both Groups 3 and 5. In Group 3, the posterior part of tympanic isthmus was less aerated than the anterior part of tympanic isthmus. In Group 5, all locations were filled with soft tissue density except the supratubal recess and the mesotympanum, where some degree of aeration was observed. These results indicate that blockage of the ventilatory passages is not essential for formation of an attic cholesteatoma. Soft tissue density in HRCT is not the cause, but rather, the result of extension of a cholesteatoma. PMID- 1512650 TI - [Intraluminal pressure profiles in the pharyngeal phase in both normal and abnormal subjects]. AB - Intraluminal pressure change in the pharyngeal phase of swallowing was measured by the station pull-through method, in which a pressure transducer probe was being withdrawn at each 1 cm step from a segment 25 to 8 cm from the nostril. The probe had an outside diameter of 5.0 mm in size and was loaded with two miniature pressure transducers 3 cm apart from each other. Electromyogram of the suprahyoid muscles was simultaneously recorded with a surface electrode as an index of the second phase of deglutition. The three formats to analyze pressure wave forms in swallowing were designed as followings; a swallowing pressure curve showing peak values at each level, a conduction curve of swallowing pressure indicating the times when the peak of the pressure appeared at each level, and a calculation of the onset of relaxation and its duration at the portion of high pressure zone of the upper esophagus (UHPZ). Analyses of the data in 30 normal subjects revealed the following results. 1) All showed swallowing pressure curves with 3 peaks at the levels of the velopharynx, hypopharynx and cervical esophagus. 2) Normal ranges of the pressure at each level of the peak were 48.2-139 mmHg, 46.4-132 mmHg and 9.0-111 mmHg, respectively. 3) Conduction curves of swallowing pressure showed an "S" like figure in all and the gradient was steep at the level of the oropharynx and hypopharynx. 4) The duration of relaxation at the paroxysmal end within the UHPZ was shorter than that at the distal in all. The normal range of the duration of relaxation at the paroxysmal end was 365-833 msec. Profiles of swallowing in 130 patients with dysphagia showed the following results. 5) Pressure curves in swallowing were classified into 4 pathological patterns of curve depending on the site of a lesion. 6) Two of all showed an abnormal pattern of the conduction curve, which was supposed to be originated by a disorder in the preprogrammed process in swallowing. 7) Two of all also showed abnormally earlier onset of relaxation within the UHPZ. 8) Of all, 3 showed short duration of relaxation within the UHPZ abnormally. PMID- 1512651 TI - [The effect of aging on observation in hearing in the same individuals over a 5 year period]. AB - The purpose of this study was to investigate the process of changes in hearing of pure tones with aging. Among individuals who had undergone thorough medical examination for the purpose of annual health-checks, 293 males (586 ears) whose hearing level had been examined for five years or more were enrolled in this study. Cases having conductive deafness or known sensori-neural deafness were excluded. Since the most typical change with aging is observed at 8 kHz, the investigation was carried out only on hearing at 8 kHz. Hearing level increasingly declined with advancing age. Hearing distribution for young subjects showed a peak in the normal hearing level range. This peak decreased with aging, and another peak appeared at 50 dB. Investigation of differences in hearing in the individuals over the five years showed that most subjects had a hearing level difference of 0 dB up to 54 years of age. From 55 years old onward, however, the difference was 5 dB. This indicates that gradual deterioration of hearing level with aging occurs most frequently. On the other hand, in some subjects, deafness progressed faster. Thirty-four and a half percent of the subjects had deteriorations of 20 dB or more in a single year during the entire observation period. A deterioration of 20 dB or more was noted in 4% of the young and 8% of the elderly. Such rapid progression of deafness was believed to be involved in formation of the 50 dB peak in the hearing distribution. PMID- 1512652 TI - [Postural control in the elderly]. AB - In order to investigate postural control in the elderly, a stabilometric investigation including fast Fourier Transform (FFT) analysis was conducted in three different age groups. The oldest group was composed of 16 subjects who ranged in age from 75 to 86 years: another group consisted of eight 65 to 74 year olds; the control group was composed of 21 young students. The subject was instructed to stand and look for 30 seconds at a spot in a CRT 50 cm ahead of his eyes, and to control body sway as indicated by the gravitational spot in the CRT. The subject was then told to stand with eyes closed for 30 seconds. Next, a 100 Hz vibratory stimulation was applied to the bilateral Achilles tendon in each trial. The data was filtered with a 10 Hz high cut filter and digitized at 25 Hz, and subsequently analyzed by a microcomputer (PC9801 VM 2). Thus, statistical analysis was performed in terms of area, length, and total frequency spectra from 0.10 Hz to 10.0 Hz in both lateral and antero-posterior directions. Sixteen power spectra of 0.249 Hz step from 0.10 to 3.96 Hz were demonstrated in the CRT and were also compared with those of the young group. When standing naturally, significant increases in body sway were found in terms of area, length, and total frequency spectra in the most elderly group as compared with the other two groups. There was no significant change in Romberg ratio between the elderly and the young groups. However, FFT analysis confirmed the influence of visual cues. When vibration was applied, no increases in body sway with regard to these parameters were demonstrated in the elderly, whereas significant increases were found in the young control group. This was especially evident in the eyes-closed trials, as previously reported. There were few increased frequency ranges in either lateral or antero-posterior sway in the elderly. This might suggest that proprioceptive afferent information play a less important role in elderly than in young subjects. When the subject was requested to minimize his own sway by utilizing visual feedback, no difference was found in this parameter between the elderly and young groups. However, FFT analysis of the elderly group revealed an increase of the power spectra close to 1.0 Hz in both lateral and antero posterior sway, whereas increases of approximately 1.0 and 2.0 Hz in the power spectra and a decrease in the power spectrum from 0.10 to 0.29 Hz were found in both directions in young subjects.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1512653 TI - [Morphological findings of the tympanic plexus]. AB - A morphological study of the human tympanic plexus was performed. The tympanic nerve patterns on the promontory were classified into two types. The first was the single nerve trunk type, the second the type of nerve which divides into anterior and posterior branches. A tubal branch and a caroticotympanic branch on the promontory were both present in about 90% of the ears studied. Many ganglion cells were distributed on the tympanic plexus. It was concluded that these ganglia were autonomic, based on the nature of their fine structure. We speculate that these ganglia are parasympathetic and that they modulate the functions of vasodilators and secretory glands in the mucosa of the middle ear. In addition, we conducted a fiber analysis of the tympanic nerve and the lingual branch of the glossopharyngeal nerve and made a comparison between them. PMID- 1512654 TI - [Immuno-injury to the inner ear auditory system following secondary endolymphatic sac immune response]. AB - This study investigated immuno-injury to the inner ear auditory system following inner ear immune response in the guinea pig. The endolymphatic sac (ES) was directly challenged with keyhole limpet hemocyanin (KLH). Auditory brainstem response with click sound stimulation was assessed pre and post KLH challenge of the ES. In systematically presensitized animals, secondary KLH challenge to the ES produced significant elevation of the mean threshold level on day 3 and 17 as compared to that of pre challenge levels. However, no significant prolongation of the latency (N1-N3) was observed. On the other hand, neither phosphate buffered saline injection into the ES nor primary KLH challenges of the ES were capable of elevating the threshold level and changing the latency. These results indicate that elevation of threshold was apparently induced by a secondary immune response of the ES, not by nonspecific mechanical damage to the ES, the central auditory system or KLH toxicity to the inner ear, suggesting that local immune response of the ES is a possible pathogenesis of sensorineural hearing loss. PMID- 1512655 TI - [A clinical observation of cases which was suspected of congenital cholesteatoma]. AB - Four cases which was suspected of congenital cholesteatoma were treated in the past 15 years. The age of the patients ranged from 4 to 17 years. In all cases, the cholesteatoma arose in the middle ear. In one case the cholesteatoma extended into the mastoid cavity. Tympanoplasty of colummella type III was indicated. Postoperative hearing gain was from 20 to 30dB. Although the incidence is low, otolaryngologists must be aware of congenital cholesteatoma when treating conductive hearing loss with a normal ear drum. PMID- 1512656 TI - [A cinefluorographic study of hyoid bone movement during deglutition]. AB - A quantitative study was performed to analyze movement of the hyoid bone on swallowing in 71 patients with pharyngo-laryngeal neurosis (44 males, 27 females), who had no abnormal findings either morphologically or functionally. The lateral X-ray cine (30 frames/sec) was taken while the patients swallowed the contrast medium in the upright position, and precise movement of the hyoid bone was examined using a motion analyzer. The movement was divided into 5 phases; initial slow elevation from the resting position (1st elevation phase), then a quick upwards shift to the highest position (2nd elevation phase), where the hyoid bone remained temporarily (static phase), followed by rapid and slow descending shifts towards the resting position (1st and 2nd descending phase, respectively). The resting position of the hyoid bone is significantly lower in males than in females and it seemed to get lower with age in both sex. When compared to the younger group (age 10-30), the older group (age 60-70) had significantly more distance and longer duration of deglutition in the 1st elevation phase, whereas the 2nd elevation phase did not differ among the age group. The results of this study indicate that prolongation of the time and distance of the 1st elevation phase are more significant in the older group, which may well explain the cause of delayed of deglutition. PMID- 1512657 TI - [Cryptotia: morphometric characteristics and statistical observations]. AB - PURPOSE: In the present study we made actual measurements of the normal and affected auricles of patients with unilateral cryptotia and performed a comparative statistical analysis. We also made a compilation of our own cases and other cases reported in Japan, and reported the results of our statistical analyses. METHODS: The subjects of this survey were 36 patients who came to our outpatient clinic with a chief complaint of cryptotia between 1983 and 1990. Measurements of auricle were made according to the Martin method. We also compiled all cases of cryptotia reported in the Japanese literature to date in which the sex of the patients and affected side were clearly recorded and reviewed associated abnormalities and familial occurrence. RESULTS: Auricle measurements of auricle showed the vertical axis of the affected auricle to be significantly shorter than normal, revealing severe shortening of the upper 1/3 of the auricle. There was no statistically significant difference between the normal and affected auricles on the horizontal plane. The results of our compilation of reports in the literature to date show a male-female ratio of 2:1, a right-left-bilateral ratio of 5:2:3, the presence of other anomalies in 9.2% (7/76), and familial occurrence in 6.4% (15/236). CONCLUSIONS: (1) Based on measurements of auricle, cryptotia is defined as a deformity of the upper 1/3 of the auricle and is produced by the sum total of force vectors operating inferiorly and medially. Moreover, based on the data obtained as a result of the measurements performed in this study, there was greater deformity along the vertical axis, and the downward vector was obviously stronger than the inward vector. (2) There were 3 cases of unilateral cryptotia with an adhesion-like deformity of the helix in the normal ear, and the theory that the upper portion of the auricle becomes embedded secondary to cartilage deformity seemed plausible. (3) A compilation of cases in Japan showed a male-female ratio of 2:1 and a right-left-bilateral ratio of 5:2:3, differing little from the ratios in our cases. (4) Familial occurrence in our cases was found in the patient's mother of 2 cases and a male cousin and uncle in 1 case each, suggesting a strong hereditary influence. PMID- 1512658 TI - Results of combined surgery on the superior oblique and horizontal rectus muscles for A-pattern horizontal strabismus. AB - Results obtained in 32 patients with A-pattern horizontal strabismus and overacting superior oblique muscles treated with combined bilateral superior oblique tenotomies and bilateral symmetric surgery on the horizontal rectus muscles were analyzed retrospectively. The magnitude of reduction of the A pattern correlated positively (r = 0.69) with the size of the preoperative A pattern. Overall, 27 of the 32 patients (84%) had a satisfactory reduction in their A-pattern. Esodeviated patients received less correction in the primary position than exodeviated patients. Postoperative complications were minimal if the superior oblique tendon was hooked under direct visualization, and minimal dissection was performed on the surrounding tissue prior to transecting it near the nasal side of the superior rectus muscle. PMID- 1512659 TI - VEP acuity, FPL acuity, and visual behavior of visually impaired children. AB - Forced-choice preferential-looking (FPL) and pattern-visual-evoked potential (VEP) acuity tests were conducted with 42 children with bilateral moderate to severe visual impairment (age, 4 months to 9 years). Within this group of children, FPL acuity testing was more successful than VEP acuity testing (98% versus 64%). Mean FPL acuity was better than mean VEP acuity (20/155 vs 20/290, P less than .002). For the children who completed both FPL and VEP acuity tests, an acuity difference score (FPL minus VEP) was derived, and compared to difference scores based on normative data. Significant differences were found between visually impaired (VI) and control difference scores (P less than .001). Difference scores of VI were larger than and opposite in sign to the control scores. Rating scores of visual behaviors supported the concurrent validity of the FPL acuities (P = .01), but not the VEP acuities. PMID- 1512660 TI - Anterior polar congenital cataract and corneal astigmatism. AB - Seven eyes of six patients with anterior polar congenital cataract were examined. All patients presented with corneal astigmatism greater than 1.50 diopters. The combination of these two anomalies has often been responsible for amblyopia and occasionally for squint. The association of corneal astigmatism with this type of congenital cataract is possibly due to a delayed separation of the lens from the surface ectoderm during fetal development and thus may be considered a new syndrome. PMID- 1512661 TI - Eye muscle prosthesis. AB - We inserted a silicone rubber elastic band along the course of a paralyzed lateral rectus and of a paralyzed superior oblique to restore alignment and to provide a spring against which the antagonist could pull. The lateral rectus band has been in place for 7 years. It provides alignment and a field of single binocular vision of 20 degrees. The superior oblique band has been in place for 17 months. It provides alignment and single vision over 30 degrees from the primary position except for a restriction in upgaze-adduction to 25 degrees (Brown syndrome) and in downgaze-adduction to 20 degrees. Such engineered elastic bands are a useful addition to current surgical techniques for management of cases of paralysis and restriction. PMID- 1512662 TI - Factors affecting long-term results of successfully treated amblyopia: age at beginning of treatment and age at cessation of monitoring. AB - The visual acuity of 104 patients who had previously been successfully treated for unilateral amblyopia by occlusion of the good eye was examined 6.4 years, on average, after cessation of treatment. Three age groups were defined, according to the age at which treatment was started: younger (2 to 5.5 years), middle (5.5 to 8 years) and older (above 8 years). In 55% of the patients, the long-term follow-up examination revealed deterioration of the visual acuity. In patients in whom amblyopia had been monitored at least up to the age of 9 years, the age at which treatment was started did not significantly affect the mean amount of deterioration or the mean visual acuity noted at the long-term follow-up examination. PMID- 1512663 TI - Central nervous system involvement in Leber congenital amaurosis. AB - Sixteen patients with ocular criteria of Leber congenital amaurosis (LCA) were studied. Neurological examination was normal in 11 of 16 patients. The electroencephalogram was normal in six of eight patients, while two had nonspecific theta slowing. Computerized tomography of the brain was normal in two of five; hypoplasia of the cerebellar vermis was seen in one, and mild to moderate ventriculomegaly was seen in two of five. Six patients underwent the verbal subtests of the Wechsler Intelligence Scale and a detailed battery of neuropsychological tests. Subtests dependent on early environmental influences were most severely affected, while culture-free subtests showed average or well above average performance. These results strongly support the hypothesis that children with LCA may be capable of normal cognitive functioning, although they perform poorly on standard IQ tests. This is related to their early environmental and sensory deprivation, rather than to a primary central nervous system dysfunction. PMID- 1512664 TI - Aplasia of the optic nerve: report of three cases. AB - Aplasia of the optic nerve is a very rare congenital anomaly characterized by an absence of optic nerve fibers, retinal ganglion cells, and the retinal central blood vessels. It may be associated with a wide range of other congenital abnormalities. In the present article, three cases of aplasia of the optic nerve are described. Its pathology and clinical features are reviewed. PMID- 1512665 TI - Comparison of on- and off-axis photorefraction with cycloplegic retinoscopy in infants. AB - We have compared the performance of an off-axis (knife-edge) photorefractor with that of an on-axis (isotropic) system. Normal infants and children between the ages of 8 and 208 weeks were photographed with each camera both with and without cycloplegia. Refractive errors were estimated for each technique based on equations derived from ray-tracing. These refractions were compared to the results of retinoscopy under cycloplegia. Sensitivity and specificity of the two photorefraction systems were evaluated as a function of the magnitude of meridional hyperopia defined by retinoscopy. We also examined the effect of varying the photorefraction screening criterion. Thirteen percent of the infants in the screening sample presented with +3.50 diopters or more of meridional hyperopia. Using this level of ametropia as a referral criterion, the sensitivity and specificity of the off-axis system for infants without cycloplegia were 83% and 72%, respectively. For the on-axis system, sensitivity and specificity values were 85% and 53%. The use of cycloplegics did not significantly improve the performance of either system, but rather their use degraded the specificity of the on-axis system in the presence of moderate refractive errors. The results of the present study indicate that both on- and off-axis systems are effective in identifying highly ametropic infants, but that the off-axis system results in significantly fewer false positives. Moreover, the off-axis system has the advantages of an inherently greater dynamic range for a fixed camera design, and also more easily interpreted photographs. PMID- 1512666 TI - Periodic alternating esotropia. AB - Periodic alternating esotropia (PAE) is a rare ocular motility disturbance observed in association with periodic alternating gaze deviation (PAG) or periodic alternating nystagmus. We examined a 9-month-old developmentally delayed girl who showed PAE occurring synchronously with PAG. The ocular motility disorder consisted of rhythmic alternating fixation with the right eye in abduction, a left face turn and esotropia of the left eye (90 seconds), a changeover phase (10 to 15 seconds) during which the eyes are straight and the head is upright, then fixation with the left eye in abduction, a right face turn, and esotropia of the left eye (90 seconds). There was no spontaneous jerk nystagmus present. These findings continued incessantly during a follow-up period of 18 months. Magnetic resonance imaging revealed pronounced cerebellar vermis hypoplasia. Only three clinically similar cases have been previously reported, but none had been studied with modern neuroimaging techniques. PMID- 1512667 TI - Rigid gas permeable contact lens correction of aphakia following congenital cataract removal during infancy. AB - Rigid gas permeable (RGP) contact lenses were prescribed and worn with little difficulty by 10 consecutive aphakic infants. Fluoroperm 92 lenses were used instead of silicone lenses (Bausch & Lomb) because of their lower cost, ease in handling, flexibility in design, and better neutralization of astigmatism. Lenses were worn on a daily wear basis (with occasional overnight wear) to reduce the risk of keratitis. Keratometry readings were taken at the time of surgery with the patient in a supine position. Trial lens fitting was performed 1 to 7 days later using a Burton Lamp. None of the patients developed keratitis, corneal neovascularization, or the sucked-on-lens syndrome. The lenses were well tolerated and the parents soon became adept at handling them. We now use RGP lenses as our lens of choice when treating aphakic infants. PMID- 1512668 TI - The optic disc in Leber congenital amaurosis. AB - The typical fundus appearance in Leber congenital amaurosis (LCA) in infancy is normal. Later in childhood, clinical heterogeneity develops and a variety of fundal abnormalities may be seen. These commonly include optic atrophy, retinal arteriolar attenuation, and a variety of pigmentary changes. We retrospectively reviewed the optic disc findings of 77 patients with LCA whom we had examined to confirm our clinical impression that the optic discs are frequently normal. Age at examination ranged from infancy to the fourth decade. The optic discs were normal in 53 (69%) of the 77 patients examined; 18 (23%) had varying degrees of optic atrophy; 2 (3%), pseudopapilledema; and 1 (1%), grey discs. The optic discs could not be seen in 3 (4%) patients. We conclude that the optic discs are frequently normal in appearance, even in older patients with LCA. PMID- 1512669 TI - Subretinal neovascularization in a 10-year-old child. PMID- 1512670 TI - Orbital childhood acute lymphoblastic leukemia as the initial presentation. PMID- 1512671 TI - Maximum likelihood estimates of the ability of the MMPI and MCMI personality disorder scales and the SIDP to identify personality disorders. AB - The ability of the Minnesota Multiphasic Personality Inventory (MMPI) and Millon Clinical Multiaxial Inventory (MCMI) personality disorder scales and the Structured Interview for DSM-III Personality Disorders (SIDP) to identify personality disorders was estimated statistically using 122 subjects. Each technique was reasonably accurate when various diagnoses were excluded, but they were quite variable in identifying members of specific diagnostic categories. The same general pattern was seen when the disorders were combined into three general diagnostic clusters. The techniques excluded cluster membership fairly well, although there was little agreement across techniques for identifying cluster membership. The MCMI, however, was moderately adept at identifying membership in all three clusters. It was suggested that these instruments should be used cautiously in clinical settings and that additional data on their performance be obtained. PMID- 1512672 TI - Early memories and the criminally dangerous. AB - We demonstrated the efficacy of using early memory (EM) data to distinguish postdictively criminally dangerous from nondangerous psychiatric patients. Dangerous patients (n = 30) had been adjudicated not criminally responsible (NCR) for felonies, whereas nondangerous psychiatric patients (n = 30) had no convictions for aggressive offenses. Groups were comparable in age, IQ, socioeconomic status (SES), marital status, and diagnoses. Group racial compositions, however, were significantly different. Statistical analyses were thus performed to clarify the potential effect of this racial confound. Overall, 73% of the dangerous and nondangerous patients were accurately classified via a newly developed EM scoring system, the Early Memory Aggressiveness Potential Score System (EMAPSS). Of those classified as dangerous, 15 of 16 (94%) were actually dangerous. The false-positive rate was an impressively low 6%, suggesting EM aggression is highly predictive of dangerousness postdictively. PMID- 1512673 TI - Validity of Harris and Lingoes MMPI subscale descriptors in an outpatient sample. AB - The validity of the Minnesota Multiphasic Personality Inventory (MMPI) subscales described by Lingoes (1960) along with his predicted correlates was investigated using clinicians' ratings of 85 outpatient therapy clients. Of the 68 predicted correlates, 30 were significant and supported the description of 16 of the subscales, but not necessarily their ability to discriminate nuances of pathology. The most significant correlations were obtained by the D, Pd and Sc subscales, the fewest by the Hy, Pa and Ma subscales. The lack of significant results for 12 subscales is discussed in terms of subscale unreliability, subscale length, or insufficiencies in the criteria or sample tested. The possibility that several of the unsupported subscales may function in the detection of defensiveness was considered. PMID- 1512674 TI - The Ego Impairment Index and schizophrenia: a validation study. AB - This study is an extension of our work on a new scale, the Ego Impairment Index (EII; Perry & Viglione, 1991). The index is theoretically based on Beres's (1956) model of ego assessment and was empirically developed on a sample of melancholic, depressed outpatients, diagnosed according to the Diagnostic and Statistical Manual of Mental Disorders (3rd ed. [DSM-III]; American Psychiatric Association, 1980). The EII is derived from the Rorschach Inkblot Test and offers a single composite score of ego impairment. This study validates the use of the EII with a heterogeneous sample of schizophrenic patients. In support of the trait-like characteristics of the scale, the EII continues to be expressed as a single factor, with a correlation of .98 when comparing the original factor derived from a melancholic population with this sample of schizophrenic patients. Significant correlations were also found between the EII and other clinical indices, including the Magical Ideation Scale, the Schizophrenia Index, and the Minnesota Multiphasic Personality Inventory (MMPI). Finally, the EII was found to differentiate between a paranoid subgroup and a mixed undifferentiated/disorganized subgroup who theoretically have more ego impairment. These results offer support for the use of the EII as an empirical means of quantitatively and qualitatively assessing thought disorder within a theoretical framework. Further research is needed to understand the application of the EII across different diagnostic groups and its relationship to other indices of psychological disturbance. PMID- 1512675 TI - Barren Rorschachs: a conceptual approach. AB - A discussion is presented of five Rorschach protocols that appear to meet the criteria proposed by Exner and Weiner (1982, p. 31) for "brief and barren" Rorschach protocols. The protocols were obtained from a social service agency treating abused, neglected, disturbed, and delinquent youths. An attempt is made to bring to bear a conceptual approach to these Rorschachs, so that they may be seen as clinically valuable and revealing, hence not "invalid" diagnostic protocols. Emphasis is placed on the subjects' approach to the task, the subject examiner interaction, and the meaning of the subjects' ostensibly peripheral comments. Recommendations are offered regarding ways to maximize the clinical utility of such protocols. PMID- 1512676 TI - Rorschach blends, IQ, and the effect of R. AB - A correlation of .351 was found between the Rorschach blend score and the Wechsler Adult Intelligence Scale Full Scale IQ (WAIS FSIQ) score for 70 outpatients. When the total number of responses (R) was partialed out, however, the correlation dropped to .255. We concluded that it is advisable to take into account the effects of R in validity studies showing significant but low correlations. The importance of further exploring the psychological implications of R was stressed. PMID- 1512677 TI - Self-report, peer-report, and teacher-report measures of childhood depression: an analysis by item. AB - We explored the low correlation among different types of childhood depression measures at the item level. The items from the Children's Depression Inventory (CDI), Peer Nomination Inventory of Depression (PNID), and the Child Behavior Checklist-Teacher Report Form (CBCL-T) were combined, and both first- and second order factor analyses were conducted. Results indicate that self-report, peer report, and teacher-report assessments of depression measure generally uncorrelated constructs. Second-order analysis suggests that depression as a global construct is being measured to some degree by items from all three instruments. Canonical analysis was employed to identify items that best predicted CDI, PNID, and CBL-T summary scores simultaneously. Also, the relationship between specific items with similar content was investigated. Results from these analyses generally supported a conclusion that the three types of measures yield scores that are primarily independent and that the use of summary scores is not masking stronger relationships within measures. These findings have implications for clinical practice and construct elaboration. PMID- 1512678 TI - The effect of MMPI-2 on scoring of special scales derived from MMPI-1. AB - Twenty-nine special scales derived from the Minnesota Multiphasic Personality Inventory (MMPI-1; Hathaway & McKinley, 1983) were scored from MMPI-I and MMPI++ 2 (Hathaway et al., 1989) items for a normal and a psychiatric sample. Resulting pairs of mean scores were compared. Absolute differences were found to be small but statistically significant. We concluded that, despite the statistical significance, the small absolute differences suggest that most of the MMPI-I special scales probably can be scored and interpreted from MMPI-2 items. Further research along this line is necessary. PMID- 1512679 TI - Object relations, defensive operations, and affective states in narcissistic, borderline, and antisocial personality disorder. AB - Rorschach data were used to psychometrically "map" the internal psychological operations of three Cluster B personality disorders, listed in the Diagnostic and Statistical Manual of Mental Disorders (3rd ed., rev. [DSM-III-R]; American Psychiatric Association, 1987), all of which may be organized at a borderline level. Psychopathic antisocial subjects (P-APDs) and narcissistic subjects (NPDs) were highly narcissistic. NPD subjects, however, produced more indices of anxiety and attachment capacity and fewer scores related to borderline object relations and damaged identity. P-APDs and borderline subjects (BPDs) produced similar mean numbers of borderline object relations; however, the BPDs were more anxious, produced more unsublimated aggressive and libidinal drive material, and evidenced greater potential for attachment. BPDs were also less narcissistic than both P APDs and NPDs. Nonpsychopathic antisocial subjects (NP-APDs) were less borderline than P-APDs and BPDs, less narcissistic in terms of a stable grandiose self structure than NPD and P-APDs, produced less evidence of attachment capacity than NPDs and BPDs but more than P-APDs, and were similar to BPDs in their proneness to anxiety. The outpatient NPDs and BPDs produced more idealization responses than the incarcerated antisocial personality disorder (APD) groups. We conclude that the behavioral descriptions offered for these three Cluster B personality disorders, when used in conjunction with information such as level of personality organization (Kernberg, 1984), level of psychopathy (Hare, 1980, 1985), and outpatient versus inpatient research settings, may have greater intrapsychic specificity than previously thought. PMID- 1512680 TI - Rorschach changes following brief and short-term therapy. AB - Two groups of 35 patients each, one treated with brief therapy, averaging 14.2 sessions on a once per week basis, and the other group, treated with a short-term type of therapy, averaging 47 sessions on a once per week basis were administered the Rorschach and the Katz Adjustment Scales-Form S three times. The first administration took place before entering therapy. The brief therapy group was tested a second time at termination of treatment and again 8 to 12 months following termination. The short-term therapy group was tested the second time at therapy termination and the third time 10 to 12 months after termination. Each group reported substantially fewer symptoms at termination and continued to report about the same level of symptom reduction at the second retest. The Rorschach data seem to provide an ample basis from which to argue that considerable improvement occurred in the psychological organization and/or operations of both groups, and this appears to have some confirmation in the self report data. PMID- 1512681 TI - Psychometric properties of the revised UCLA Loneliness Scale and two short-form measures of loneliness in Zimbabwe. AB - The cross-cultural reliability in Zimbabwe of the Revised University of California at Los Angeles (UCLA) Loneliness Scale and two short forms of the Revised UCLA Loneliness Scale were investigated. Subjects comprised a sample of 1,354 adolescents and another sample of 754 adults. The reliability of the Revised UCLA Loneliness Scale was acceptable. The internal consistency of an eight-item short form of the Revised UCLA Loneliness Scale was adequate, but the reliability of a four-item short form was low. Factor analysis of the Revised UCLA Loneliness Scale, which yielded two factors similar to those reported in North America by Zakahi and Duran (1982) supported the construct validity of the Revised UCLA Loneliness Scale in Zimbabwe. The Revised UCLA Loneliness Scale and the eight-item short form were highly correlated, but this association was spuriously elevated by the fact the eight-item short form is part of the full scale. Factor analysis of the eight-item short form suggested that this scale does not consistently reflect the factor structure of the full scale. We concluded that the Revised UCLA Loneliness Scale possesses acceptable reliability and factorial validity in Zimbabwe and that the eight-item version is superior to the four-item form of the Revised UCLA Loneliness Scale as a short loneliness measure. However, additional refinements may be needed to further improve the eight-item short version. PMID- 1512682 TI - Psychometric properties of the Depressive Experiences Questionnaire for adolescents. AB - Items of the Depressive Experiences Questionnaire (DEQ) were rephrased and simplified to make them appropriate for younger subjects. This adolescent form of the DEQ (DEQ-A) was administered to high school students; a factor analysis revealed three factors that were highly congruent in female and male students and with the three factors of the original DEQ. Internal consistency as well as short and long-term reliability for each of the 3 DEQ-A factors were at acceptable levels. Each factor correlated highly with its counterpart factor in the original DEQ, especially the Dependency and Self-Criticism factors. Correlations of the DEQ-A factors with other measures of depression essentially replicate relationships found between these measures of depression and the original DEQ for adults. The reliability, internal consistency, and validity of the DEQ-A indicate that it could be useful in studying depressive experiences in younger adolescents. PMID- 1512683 TI - No evidence for female-to-female HIV transmission among 960,000 female blood donors. The HIV Blood Donor Study Group. AB - The frequency of female-to-female HIV transmission was assessed among 960,000 female blood donors at 20 large U.S. blood centers during 1990. Of 144 HIV seropositive women identified, 106 were interviewed. None of the interviewed women reported sex exclusively with women since 1978. Three seropositive women reported sex contact with women as well as with either bisexual men or men who had used i.v. drugs. In this large population, we identified no woman who was infected with HIV from sexual contact with another woman. PMID- 1512685 TI - Trends in HIV infection among intravenous drug users in Innsbruck, Austria. AB - The first HIV test among intravenous drug users (IVDUs) at the AIDS clinic and/or the drug dependency clinic of the University of Innsbruck was the basis for the calculation of the proportions of those testing HIV seropositive annually over the period 1985-1990. The numbers testing HIV seropositive at the drug dependency clinic declined drastically, from 72.2% in 1985 to 12.5% in 1990 (chi 2 = 29.62, p less than 0.0001), whereas they rose at the AIDS clinic during this period, from 48.4% to 100% (chi 2 = 5.82, p = 0.016). Overall 132 of the 268 (49.2%) individuals examined tested HIV seropositive. There were 102 individuals of the original 146 seronegative IVDUs who were retested, for an overall incidence rate of HIV seroconversion of 5.8/100 persons-years. Risk of seroconversion was associated with a steady sexual partnership with an HIV seropositive IVDU and with an age of less than or equal to 25 years at study entry (13.1 versus 8.7/100 persons-years). No seroconversions occurred in the subgroup of patients treated by the methadone maintenance treatment program. The cumulative incidence (Kaplan Meier) rate for HIV seropositivity after 64 months was 22%, lower than the proportions testing HIV seropositive found in 1985 at each of the two clinics, which suggests that the speed of the spread of the epidemic of HIV infection among IVDUs has slowed in our region. Counseling of IVDUs should emphasize the risks of sexual acquisition, particularly among persons with steady relationships who may not perceive their risk. PMID- 1512684 TI - Relation between hospital experience and in-hospital mortality for patients with AIDS-related Pneumocystis carinii pneumonia: experience from 3,126 cases in New York City in 1987. AB - There is marked debate about whether outcomes of care, particularly mortality, vary as a function of hospital and physician experience with a disease. This issue is especially important with respect to AIDS because greater than 200,000 individuals have now been diagnosed with this disease. We analyzed discharge data for 3,126 persons with AIDS who had Pneumocystis carinii pneumonia and who were treated at one of 73 New York City hospitals in 1987. In-hospital mortality was 25%. Factors associated with higher chances of short-term death were older age, being black, not having private health insurance, and being severely ill. A logistic regression model indicated that after controlling for differences in patient and hospital characteristics, the chances of death decreased when care was given at hospitals with higher caseloads of patients with Pneumocystis carinii pneumonia. Our findings suggest that hospital experience may decrease mortality in this subset of patients with human immunodeficiency virus disease, although it is unknown whether this is due to differences in quality of care. PMID- 1512686 TI - Poor sensitivity, specificity, and reproducibility of detection of HIV-1 DNA in serum by polymerase chain reaction. The Transfusion Safety Study Group. AB - A series of recent studies have reported detection by the polymerase chain reaction (PCR) of cell-free human immunodeficiency virus type 1 (HIV-1) DNA (as opposed to virion RNA) in serum from both seropositive and seronegative persons. To evaluate the sensitivity, specificity, and reproducibility of PCR detection of cell-free HIV-1 DNA, we distributed coded panels containing 98 serum specimens obtained from well-characterized, infected individuals and control blood donors to the two laboratories with reported experience with this technique. Positive results were reported with HIV-1 gag primers (SK38/39) for 48 of 188 separate PCR determinations on DNA extracts from 44 serum samples from seropositive patients (25.5% sensitivity). HIV-1 gag signal was also reported for 28 of 151 PCR determinations on 34 samples from noninfected blood donors (18.5% false-positive rate). PCR for HIV-1 env DNA performed in one laboratory was negative on all specimens from seropositive and seronegative patients. Results for cell-free HIV 1 gag and human genomic (beta-globin or HLA DQ-alpha) DNA were inconsistent on replicate and serial specimens evaluated within each laboratory and between laboratories. These results indicate that current techniques for detecting cell free HIV-1 DNA in serum lack adequate sensitivity, specificity, and reproducibility for widespread clinical applications. PMID- 1512687 TI - Diagnosis of HIV infection with instrument-free assays as an alternative to the ELISA and western blot testing strategy: an evaluation in Central Africa. AB - The efficiency of an alternative instrument-free testing strategy was evaluated using a membrane-based rapid screening assay (HIVCHEK and its new version HIVCHEK1 + 2) in serial combination with a particle agglutination assay (SERODIA HIV). Among 1,054 Zairian individuals at high risk of HIV infection, 573 were Western blot-positive for HIV-1 (54.4%) and none were Western blot-positive for HIV-2. In this group, the sensitivities of the serial combination HIVCHEK plus SERODIA-HIV and HIVCHEK1 + 2 plus SERODIA-HIV were 98.1 and 98.2%, respectively, and the specificities were 99.6 and 99.5% compared with HIV-1 Western blot. The positive predictive values were 99.6% for HIVCHEK plus SERODIA-HIV and 99.5% for HIVCHEK1 + 2 plus SERODIA-HIV; the negative predictive values were 97.8 and 97.9%, respectively. Among 1,495 pregnant women, 90 were Western blot-positive for HIV-1 (6.0%), and 54 of 1,510 blood donors were HIV-1 Western blot-positive (3.6%). None were positive for HIV-2. The sensitivities of HIVCHEK plus SERODIA HIV and HIVCHEK1 + 2 plus SERODIA-HIV in these groups were 98.6 and 99.3%, respectively, and the specificities were 99.8 and 99.7%. The positive and negative predictive values of HIVCHEK plus SERODIA-HIV were 96.6 and 99.9%, respectively, and they were 94.1 and 99.9%, respectively, for HIVCHEK1 + 2 plus SERODIA-HIV. These instrument-free testing strategies are efficient alternatives for serodiagnosis of HIV-1 infection, although their cost should be further reduced. PMID- 1512688 TI - Clinical and laboratory profile of AIDS in India. AB - The clinical features and results of laboratory investigations of the first 19 Indian patients with AIDS seen in our hospital are presented. Weight loss, fever, and diarrhea were the most common symptoms. Tuberculosis (TB) was the most common secondary infectious disease; among 13 patients, seven had only pulmonary TB, five had pulmonary and extrapulmonary TB, and one had only extrapulmonary TB. Oropharyngeal candidiasis was found in 11 patients. Other secondary infections were predominantly by virulent bacteria. Opportunistic infections other than candidiasis were infrequent; one patient had cryptococcosis, two had symptomatic cryptosporidiosis, one had noncoagulase-positive staphylococcus septicemia, and one had cytomegalovirus retinitis. Reduced lymphocyte counts (particularly of the CD4 subset), anemia, hypoalbuminemia, hyperglobulinemia, and elevated liver enzyme levels were frequent laboratory findings. Six patients are under follow up, two are lost to follow-up, and 11 have died. Lymphocyte counts less than 500/mm3 were only seen in those patients who subsequently died. Response to antituberculosis therapy was good in several patients. Thus, the clinical profile of Indian patients with AIDS is not different from the common picture of patients of low socioeconomic and poor hygienic standards; patients presented with TB, undernutrition, and multiple infections. Therefore, a large population of patients with AIDS in India will not be recognized unless they are tested for evidence of HIV infection. PMID- 1512689 TI - Eleven lymphoid phenotypic markers in HIV infection: selective changes induced by zidovudine treatment. AB - HIV infection induces substantial changes in the expression of many lymphocyte phenotypic markers as well as depletion of CD4 lymphocyte numbers. A comprehensive study was undertaken to determine whether seven lymphocyte phenotypic changes associated with HIV infection (increased CD38, HLA-DR, CD57, and CD71 and decreased CD11b, CD45RA, and leu-8) are altered by zidovudine (ZDV) administration. Levels of the four major lymphoid subsets (CD4, CD8, B, and NK cells) and changes in the serum activation markers neopterin and beta 2 microglobulin (beta 2M) were also measured. Elevated pretreatment expression of CD38 and CD71 was reduced significantly toward normal at 2 weeks by ZDV; however, CD38 and CD71 returned to pretreatment levels at different rates. The kinetics of CD38 reduction and the return to pretreatment levels were similar to those of serum neopterin and beta 2M. HLA-DR decreased in many but not all subjects. CD4 lymphocytes showed a transient increase, most evident at 8 weeks of treatment. Lymphoid phenotypes that did not show significant changes after ZDV therapy included CD57, CD11b, CD45RA, and leu-8 markers as well as CD8 T cells, CD20 B cells, and CD56 NK cells. The fact that some lymphocyte phenotypic markers change toward normal with ZDV treatment and others do not indicates that complex processes underlie immune perturbations of HIV infection. Several phenotypic markers (CD38, CD71, and HLA-DR) that are susceptible to short-term effects of ZDV (but with changes that differ from CD4 T cell changes) are surrogate marker candidates for evaluation in anti-HIV treatment. PMID- 1512690 TI - Further studies of salivary inhibition of HIV-1 infectivity. AB - An HIV-1/ATH8-cell cytopathic system was used to characterize the previously reported anti-HIV-1 activity of human saliva. Inhibitory activity was demonstrated by monitoring viable cell counts, HIV-1 p24 core antigen, and reverse transcriptase levels. Nonfiltered whole saliva, sterilized by irradiation, protected the ATH8 cells from HIV-1 infection. When HIV-1/saliva mixtures were filtered following incubation, the quantity of virus was significantly less (approximately 50%) than in HIV-1/media-filtered controls, suggesting that salivary aggregation and/or agglutination may be involved in the inhibitory activity. However, a sufficient number of apparently morphologically intact viral particles were still present in the HIV-1/saliva filtrates to lead to infection. When saliva was filtered prior to incubation with HIV-1, these filtrates showed substantial inhibitory activity, although reduced compared with that of non-prefiltered saliva. We conclude that saliva likely has several means by which to inhibit HIV-1 infectivity. PMID- 1512691 TI - Pilot study comparing the salivary cationic protein concentrations in healthy adults and AIDS patients: correlation with antifungal activity. AB - This investigation compared the salivary cationic protein concentrations of 12 healthy adult controls with those of 12 hospitalized patients with AIDS. Salivas were quantified by capillary electrophoresis using purified cationic protein standards. In parotid saliva, histidine-rich polypeptides (HRPs) 1-6, histatin 6, and lysozyme concentrations were determined. In addition to these eight cationic proteins, submandibular-sublingual saliva was also quantified for histatin 2 and the histatin 2 degradation product. When comparisons were made on the basis of individual proteins, the HRP-histatin concentrations in the AIDS patients showed either statistically significant decreases or a decreasing trend compared with healthy adult controls. When HRP-histatin concentrations were summed for each patient, there were statistically significant differences between the healthy adult controls and the individuals with AIDS in both parotid and submandibular sublingual salivas. Closer examination revealed that some individuals with AIDS had HRP-histatin concentrations that fell within the normal range of the healthy adult controls. For these individuals, lower than expected salivary antifungal values were obtained. Either decreasing histidine-rich protein concentrations and/or an inability of these proteins in saliva to interact with Candida albicans may contribute to the defective salivary antifungal activity seen in AIDS patients. PMID- 1512692 TI - Interactions of CD4+ plasma membrane vesicles with HIV-1 and HIV-1 envelope glycoprotein-expressing cells. AB - To study interactions between the human immunodeficiency virus type 1 (HIV-1) envelope glycoprotein (gp120-gp41) and the receptor in the target membrane, CD4, a new experimental system utilizing CD4-carrying plasma membrane vesicles (CD4 PMVs) was developed. CD4 PMVs were prepared by hypotonic lysis of HeLa cells expressing CD4 after infection with recombinant vaccinia virus containing the CD4 cDNA. The CD4 PMVs carried up to 680 CD4 molecules per vesicle. Their fusion with cells expressing gp120-gp41 after infection with recombinant vaccinia virus was monitored by fluorescence video microscopy by using lipophilic fluorescent dyes. Fluorescence changes as a result of fusion occurred within 30 min at 37 degrees C, and little fluorescence changes were seen with cells expressing the noncleaved HIV-1 envelope glycoprotein (gp160). The preincubation of CD4 PMVs with HIV-1 reduced its infectivity 10-fold. The CD4 PMVs were more effective in inhibiting syncytia formation than sCD4. These results demonstrate that CD4 PMVs could be used to study the mechanisms of HIV-1 envelope-mediated fusion and have the potential to inactivate HIV-1. PMID- 1512693 TI - Spectrotype of anti-gp120 antibodies remains stable during the course of HIV disease. AB - Human immunodeficiency virus (HIV) infection is characterized by a progressive decline in immune functions. The behavior of B-cell clones specifically engaged in the anti-HIV response could play a relevant role in the pathogenesis of such impairment. The spectrotype observed on isoelectric focusing and reverse blotting after antigen challenge is the serum image of antigen-specific B-cell activity and may provide some insight into Ag-dependent B-cell clone recruitment. In this study, we examined the spectrotype of anti-gp120 antibodies in a group of sera from 56 HIV-infected patients, belonging to groups II, III, and IV of the Centers for Disease Control classification, as well as in a group of 31 sera from 12 patients in a 21-month follow-up evaluation (range 7-36 months). All tested sera were positive for gp120 antibodies on Western blot. In the first group of 56 HIV infected subjects, only 19 displayed well-focused banding patterns. Among these, the spectrotype was found to be consistently oligoclonal, thus confirming clonal restriction of anti-gp120 antibodies previously described by other investigators. No correlation could be established between a particular spectrotype and phase of the disease. The follow-up evaluation in the second group of 31 sera revealed the tendency in each patient to maintain the same spectrotype throughout the course of the disease. These findings confirm clonal restriction of anti-gp120 antibodies in HIV infection and suggest that the number of B-cell clones recruited in the anti-gp120 response remains stable over the course of the disease, at least in the time range explored by us. PMID- 1512694 TI - Quantification of HTLV-1 proviral copy number in peripheral blood of symptomless carriers from the French West Indies. AB - The development of human T-cell leukemia type 1 (HTLV-1) diseases are related to an increase in the proviral copy number (VCN) in peripheral blood mononuclear cells (PBMCs). Twenty symptomless anti-HTLV-1-positive blood donors, as well as four symptomatic individuals, all from the French West Indies, were studied. The VCN in PBMCs was determined by quantitative PCR. The VCN values for asymptomatic HTLV-1 carriers (range of less than 100 to approximately 9,500/micrograms of DNA) was nearly always less than the values for symptomatic carriers (range of approximately 5,500 to approximately 29,000/micrograms of DNA). Consequently, the proportion of HTLV-1-infected PBMCs in symptomless and in symptomatic individuals ranged from less than 1/1,500 to approximately 1/16 and approximately 1/27 to approximately 1/5, respectively. No correlation could be found between VCN and age or sex, suggesting the importance of factors other than age and sex as influences on the VCN number. PMID- 1512695 TI - Detection of HIV-1 antibody in urine specimens in a region of low HIV-1 prevalence. PMID- 1512696 TI - Paid plasma donors: a risk group for HIV transmission not fully recognized. PMID- 1512697 TI - Special risks for the acquisition and transmission of HIV infection during sex in crack houses. PMID- 1512698 TI - Prednisone management of HIV-associated recurrent oral aphthous ulcerations. PMID- 1512699 TI - Apparent spontaneous regression of AIDS-related primary CNS lymphoma mimicking resolving toxoplasmosis. PMID- 1512700 TI - Smectite in HIV-associated diarrhea: a preliminary study. PMID- 1512701 TI - Microbial degradation of shrimp-shell waste. AB - A total of 40 strains of bacteria were isolated and tested for their potentiality to degrade chitin and utilize shrimp-shell waste for the production of chitinase. The activity ratio, percentage of weight loss and enzyme activity were determined for cultures exhibiting highest chitinolytic activities. The most active organisms were identified as Alcaligenes denitrificans, Bacillus amyloliquefaciens, B. megaterium and B. subtilis. The potentiality of the first two organisms to degrade chitin was reported for the first time. PMID- 1512702 TI - Technical bioenergetics and ecosystem biotechnology. AB - The present work explores some possible practical uses of bioenergetic processes (fermentation, respiration and photosynthesis) in the microbial cell for the purpose of renewable fuel production. These considerations are based on ecosystem biotechnology which include the following main points: 1. Creation of closed energy-transducing ecosystems under laboratory conditions. 2. Production of renewable energy carriers with the help of microbial communities (e.g., mixed cultures of microorganism). 3. Investigation of the role of the individual microoganism in the population or community. PMID- 1512703 TI - Utilization of organic acids and amino acids by species of the genus Bacillus: a useful means in taxonomy. AB - The type strains of 26 Bacillus species were investigated with respect to their capability to utilize 48 organic acids and 20 amino acids by using phenol red indicator plates and an amino acid analyzer, respectively. In addition, strains of Bacillus sphaericus were found to utilize many organic acids and amino acids in contrast to carbohydrates which are routinely checked. The results obtained indicated an individual utilization pattern for every species investigated, pointing to a useful taxonomic application of these tests for the genus Bacillus. PMID- 1512704 TI - Immunological homology among azoreductases from Clostridium and Eubacterium strains isolated from human intestinal microflora. AB - Azoreductases from several anaerobic intestinal bacteria have been shown to reduce azo dyes to carcinogenic aromatic amines. To evaluate the structural similarities of azoreductases from four species of Clostridium and one species of Eubacterium, a polyclonal antibody against purified Clostridium perfringens azoreductase was generated in rabbits. This antibody inhibited the azoreductase activity of all five bacteria tested. ELISA showed different degrees of binding of the antibody to various species of bacteria. In a Western blot, the antibody reacted with the purified azoreductases from all four Clostridium species and the Eubacterium species. These results demonstrate that the azoreductases from the bacteria tested share similar antigenic domains, which are probably located in the active site of the enzyme. Azoreductases from these intestinal bacteria are similar enough to be considered as a single group of enzymes with respect to their functions and antigenicity. PMID- 1512706 TI - Purification and characterization of beta-xylosidase activities from the yeast Arxula adeninivorans. AB - beta-Xylosidase activity has been detected in cell-free extracts, in culture fluids and as cell wall-bound enzyme of Arxula adeninivorans. With chromatographic procedures used to purify the activity two different forms of beta-xylosidase (denoted beta X-1 and beta X-2) from the cell-free extract and from the culture medium could be separated, but only one form (beta X-2) was present in the cell wall. Both forms are glycoproteins and were deglycosylated by endoglycosidase H treatment. The molecular masses of the enzymes under native and denaturing conditions suggest that beta X-2 is the dimer of beta X-1. M(r) of the native beta X-1 was 60 kDa and after deglycosylation 39 kDa determined by sodium dodecyl sulphate polyacrylamide gel electrophoresis. Some enzymatic properties of beta X-1 and beta X-2 and of their deglycosylated products were studied and showed, with one exception, wide similarities. The maximum activity was reached at pH 5.0 and 60 degrees C. The enzymes hydrolyze only beta-glycosidic bound beta xylopyranosides and the Km values for p-nitrophenyl-beta-xylopyranoside were determined to be 0.23-0.33 mM. The beta-xylosidase activity was inhibited competitively by xylose. The deglycosylated enzymes were, however, stronger inhibited (Ki = 2.1 mM) as their glycosylated ones (Ki = 5.8 mM). PMID- 1512705 TI - Application of newly synthesized detergents in the side chain degradation of plant sterols by Mycobacterium fortuitum. AB - Newly synthesized detergents of polyoxyethylene polyoxypropylene co-polymers (Co EOPO), polyoxyethylene polyoxypropylene adducts of the diethylene triamine (DETA EOPO), and steroidal detergents (SDD) stimulate significantly side chain degradation of plant sterols referring to both the sterol degradation and the formation of the product, 9 alpha-hydroxy-androsta-4-ene-3,17-dione (9 OH-AD), by Mycobacterium fortuitum NRRL-B-8119. Highest stimulative effects were observed with derivatives of the DETA-EOPO group. Using compounds of the Co-EOPO group optimal sterol transformation rates were found for polymers with a polyoxypropylene domain of 1400-2000 in molecular weight and with a polyoxyethylene content of 20-50%. Mostly efficient steroidal detergents tested were the 4-cholesten-3-(O-carboxymethyl)-oxime and the amino acid adducts of sterol-3 beta-chlorocarbonates. Detergents were favourably applied as pre-formed sterol-detergent complexes (9:1/w:w) in submers fermentation procedures. By treating harvested resting cells of M. fortuitum with derivatives of Co-EOPO or DETA-EOPO a considerable activation of the cells takes place concerning the sterol degradation and the formation of 9 OH-AD at a high yield in subsequent transformation process on buffer. In solubilization experiments we revealed that there is no correlation between the detergent mediated solubilization of the hydrophobic sterol substrate in the aqueous medium and the transformation activity of the bacterial cells. The detergents are assumed to interact with a multicomponent mesophase (FMCM) which is placed between cells and sterol surface and mediates the transport. PMID- 1512707 TI - Metabolic blocks in the degradation of beta-sitosterol by a plasmid-cured strain of Arthrobacter oxydans. AB - Plasmid-harbouring, sterol-decomposing organism Arthrobacter oxydans 317 was treated with sodium dodecylsulphate to obtain a plasmid-cured strain A. oxydans 317 A1 incapable of utilizing 4-androstene-3,17-dione (AD). The strain 317 A1 was unable to degrade beta-sitosterol side chain completely to form AD but could carry out partial degradation as shown by the accumulation of 3-oxochol-4-en-24 oic acid as a major metabolite and 27-norcholest-4-en-3,24-dione as a minor metabolite. The strain could form 1,4-androstadiene-3,17-dione (ADD) from 3-oxo 23,24-bisnorchol-1,4-dien-22- oic acid (BNC) to a limited extent. The existence of metabolic blocks in the conversion of 3-oxochol-4-en-24-oic acid to 3-oxo 23,24-bis-norchol-4-en-22-oic acid and further conversion to AD by the plasmid cured strain 317 A1 was suggested. Neither the formation of ADD from AD nor the conversion of AD and ADD to 9 alpha-hydroxy derivatives leading to steroid ring opening could be done by the plasmid-cured strain but the 17 beta-reduction of AD and ADD and 1(2)-reduction of ADD were not affected by the absence of the plasmid. It was proposed that plasmid determines 1(2)-dehydrogenation and 9 alpha hydroxylation of steroid ring structure in this organism. PMID- 1512708 TI - Effect of cosubstrates on the dechlorination of selected chlorophenolic compounds by Rhodococcus erythropolis 1CP. AB - Effects of aromatic and nonaromatic cosubstrates on the rate of 2,4 dichlorophenol degradation by R. erythropolis 1CP were studied under growth and nongrowth conditions. Glucose and maltose were found to accelerate 2,4 dichlorophenol (initial conc. 50 mg/l) dechlorination from 11 days to 24 and 20 h, respectively. The stimulating effect was observed within the range of glucose concentration of 0.5-2.0 g/l in the medium. Ascorbic acid at a concentration of 10-70 mg/l as a nongrowth substrate also increased the decomposition of 2,4 dichlorophenol, though at a lower degree than glucose. Experiments with washed cells showed the limiting stage of chlorophenol degradation by R. erythropolis 1CP to be, possibly, aromatic ring dechlorination after its hydroxylation. As an additional source of electrons, glucose introduced into suspensions of washed cells grown on 3-hydroxybenzoate made it possible to eliminate the bottleneck in 2,4-dichlorophenol metabolism by significantly accelerating dechlorination of 3,5 dichlorocatechol. Based on the experimental and literature data, the enzyme systems involved in 2,4-dichlorophenol degradation by the culture R. erythropolis 1CP are assumed to be nonspecific. PMID- 1512709 TI - Magnetotactic bacteria from freshwater lakes in Georgia. AB - Several species of magnetotactic bacteria were discovered in the lakes and ponds of Georgia. Electron microscopic analysis of the bacteria showed a great variety of microbial forms as well as magnetosome arrangements. Pyramidal, cubical or hexagonal magnetic grains could be seen in different species of bacteria. The linear organization of magnetic particles was prevailing, although gathered magnetosomes were also seen. Magnetometric measurement of magnetic particles obtained from coccoid bacteria was performed. Remnent acquisition curves, as well as thermomagenetic curves of investigated material showed that the magnetosomes under study contained pure single-domain magnetite. PMID- 1512710 TI - Effect of temperature and medium composition on mycelial growth of Streptomyces tendae in submerged culture. AB - To investigate the influence of culture conditions on growth of filamentous bacteria in submerged culture, S. tendae was cultivated at various temperatures and in various media. For this purpose, a temperature-controlled growth chamber was constructed, which allows the cultivation of filamentous bacteria and fungi oxygen saturated medium. To observe the development of mycelia emerging from spores, this growth chamber was mounted on a microscope stage and series of images were analyzed by an image processing system. Growth kinetics obtained in liquid culture were identical to those determined on solid media. Specific growth rate and apical extension rates of individual hyphae seemed to be higher than those observed on solid media, due to a better supply of medium in submerged culture. A two-fold increase in specific growth rate, mean apical extension rate and branching rate was observed when the temperature was increased from 27 degrees C to 37 degrees C, therefore, the length of the hyphal growth unit was not changed. Growth in synthetic media used here was considerably slower compared with complex medium. A decrease in glucose concentration from 40.0 g l-1 to 1.0 g l-1 resulted in an increase in branching rate and specific growth rate, while apical extension rate of individual hyphae was unchanged. PMID- 1512711 TI - A correlation with type of sulfonamide resistance gene in Escherichia coli and synergy between trimethoprim and sulfamethoxazole. AB - Plasmids carrying type I or II sulfonamide-resistance (Sur) genes were evaluated for their effect on synergy between trimethoprim (Tmp) and sulfamethoxyzole (Smx) in E. coli. Strain J53 containing each of three plasmids (R1, pSa, and R388) with the type I Sur gene displayed a synergistic response to Tmp/Smx; strain LE392 containing a plasmid (RSF1010) with the type II Sur gene displayed no synergy. The difference in synergy between type I and type II Sur genes might be explained by the difference in amount of resistant enzyme produced. PMID- 1512712 TI - Biosynthesis of pyrrolnitrin. Incorporation of 13C, 15N double-labelled D- and L tryptophan. AB - Experiments on the incorporation of D- and L-[alanine-3-13C,2-15N]tryptophan into the antibiotic pyrrolnitrin in Pseudomonas aureofaciens confirmed earlier conclusions about the conversion of L-tryptophan into pyrrolnitrin. They also demonstrated that a fraction of the D isomer is incorporated without breakage of the 15N-carbon bond, consistent with the operation of a second pathway from D tryptophan to pyrrolnitrin. Cell-free experiments confirmed the conversion of 3 (o-aminophenyl)pyrrole into aminopyrrolnitrin but failed to detect enzymatic oxidation of the latter to pyrrolnitrin. PMID- 1512713 TI - Oxidation of 3 beta- and 17 beta-hydroxysteroids by Nocardia rubra cells in heptane-water system. AB - Oxidation of cholesterol, beta-sitosterol, pregnenolone, androstenolone and 5 androsten-3 beta,17 beta-diol carried out by Nocardia rubra cells in a mixture of heptane-water (25:1 vol.) gave 4-en-3-oxo-steroids with the yield to 100% (cholesterol). Simultaneously oxidation of 17 beta-hydroxy group in androstendiol and in testosterone was observed as well. PMID- 1512714 TI - [Evaluation of energy metabolism on the myocardium analyzing of creatine kinase isoenzymes in rats]. AB - The purpose of this study is to evaluate the efficiency of energy metabolism in the myocardium by means of the activities of creatine kinase (CK) and CK isoenzyme following age-related change in the heart and experimental heart failure. Wistar strain male rats aged from 3 weeks to 57 weeks after birth were used. The main experimental results obtained are as follows. (1) There were differences in the compositions of CK isoenzyme of the ventricular, atrial, and papillar muscles. No apparent variation, however, was noted among the basal portions of the left and right ventricular muscles, free wall of the left ventricle, and apex. (2) Compositions of CK isoenzyme analyzed from the ventricle and atrium were clearly different. The level of CK-B subunit activity of the ventricular muscle was highest level in the 5-week-old rat, and subsequently dropped significantly in the 24-week-old rat. Thereafter, the level gradually increased with aging. Dramatic change in the energy metabolism in the myocardium occurred in rats more than 3 weeks old. (3) Decrease in activity of m-CK but increase in activity of succinate dehydrogenase analyzed from the ventricular muscle of experimental heart failure induced by monocrotaline was recognized. From these results, the author assumed that the trend of the composition of CK isoenzyme is one of the indices in the determination of the regulation of energy metabolism of the myocardium. PMID- 1512715 TI - [Prolongation of circulation time during brain ischemia-induced hypertension in the rabbit]. AB - Circulation time (CT) is markedly prolonged when arterial pressure is extremely elevated by global brain ischemia which elicits also bradycardia, decrease in cardiac output and apnea in anesthetized rabbits. To study the cause of the prolongation of CT, we measured separately CT in the large veins, cardiopulmonary circulation system (CPS) and large arteries by a dye-densitometer before and during the brain ischemia, and also examined effects of apnea and bradycardia on CT in the large veins and CPS. CT during the brain ischemia was prolonged in each portion as compared to that before the brain ischemia. The prolongation was shortest in the large veins and longest in the CPS. During the brain ischemia with apnea, there was a significant linear relationship between heart rate and the inverses of CT in the large veins, but not in the CPS. When artificial ventilation was performed during brain ischemia-induced apnea, the linear relationship became significant also in the CPS. We conclude as follows; During global brain ischemia the prolongation of CT occurs primarily in the large arteries due to constriction of the small arteries and it progresses towards the CPS and large veins. The bradycardia prolongs CT in the large veins and CPS, and the apnea may produce hypoxic pulmonary vasoconstriction which may also contribute to the prolongation of CT in the CPS. PMID- 1512716 TI - Clinical implications of acute cerebrospinal fluid changes following iophendylate myelography. AB - Clinical features and serial cerebrospinal fluid (CSF) samples of 50 patients who underwent myelography with iophendylate were studied. Forty two patients (84%) developed one or more features suggestive of meningism lasting for 2-4 days. There was significant rise in the average (mean) CSF counts from 9.81 in the premyelogram sample to 532.6 at the end of 24 hours (p less than 0.001). Both neutrophil and lymphocyte (p less than 000) count increased. At the end of one week, there was significant decrease of total cells in the CSF to 204 (p less than 0.001). Both, neutrophils and lymphocytes decreased. There was significant rise in total proteins in the 24 hours sample, but the fall at one week was not significant statistically. The sugar and chloride values did not change significantly. All CSF samples were negative for bacterial cultures. In conclusion, a significant proportion of the patients undergoing iophendylate myelography develop clinical features suggestive of meningeal irritation and change in the CSF fractions suggestive of meningitis: however these changes are transient and do not warrant institution of chemotherapy or steroids. PMID- 1512717 TI - Immunotherapeutic modification of Escherichia coli peritonitis and bacteremia by Tinospora cordifolia. AB - We present here the protective effects of an Indian medicinal plant Tinospora cordifolia as compared to gentamicin in E. Coli induced peritonitis. Pretreatment with tinospora cordifolia or gentamicin reduced mortality in mice injected with 1 x 10(8) E. coli intraperitoneally from 100% in controls to 17.8% and 11.1% respectively. This was associated with significantly improved bacterial clearance as well as improved phagocytic and intracellular bactericidal capacities of neutrophils in the Tinospora cordifolia treated group. In the gentamicin treated mice although bacterial clearance was rapid, polymorph phagocytosis was depressed. Tinospora cordifolia did not possess in vitro bactericidal activity. The results demonstrate that a "prohost approach" may be beneficial in the therapy of peritonitis. PMID- 1512718 TI - An integrated community based approach in undergraduate medical teaching of maternal and child health--an experiment. AB - The batch of 147 undergraduate medical students (Group I) were trained in maternal and child health (MCH) by allotting them families study wherein either pregnant lady or a new born child was present. The students were made to follow up these mothers and their children for three years on periodic basis by paying home visits and motivating the mothers to attend under five clinic in the community. The students educated the mother regarding child rearing with the help of medical teacher. Another batch of 140 undergraduate medical students (Group II) who did not undergo such community based training but only didactic lectures in MCH were studied as control. The knowledge and attitudes of students in both the groups were tested and compared and significantly higher knowledge and favourable attitude were found in Group I. The attendance of patients of Group I in under five clinics was compared with other children who were not adopted by medical students. The comparison was made between their weight gain, immunizational status and episodes of illness. The beneficiaries in students families had better, attendance and immunizational coverage, more weight gain and less episodes of illness. The difference was found to be statistically significant. PMID- 1512719 TI - Meckel's diverticulum in children. AB - Twenty one surgically documented cases of Meckel's diverticulum in children treated at Kasturba Hospital, Manipal since 1981 are reviewed. Of them, 14 presented with intestinal obstruction, 2 with pain abdomen, 2 with Littre's hernia and 2 were found incidentally. Only one patient presented with gastrointestinal bleeding. The clinical profile of these patients is analyzed. PMID- 1512720 TI - Conjunctival impression cytology--a study of normal conjunctiva. AB - Conjunctival impression cytology was used to study conjunctival ocular surface in 30 normal individuals in the age group of 20 to 60 years. The cytology was graded according to the classification of Nelson. Out of 30 subjects, 26 showed the features of Grade O (average age 28.33 years) and 4 showed grade 1 (average age 56.66 years). The method was very easy to perform, cheap and fast. The relationship of various cells to each other was maintained. This method can be used to study the conditions like trachoma, avitaminosis A and other disorders of conjunctival surface. It can be undertaken by a paramedical worker in an out patient clinic. PMID- 1512721 TI - Echocardiography and pulmonary artery pressure: correlation in chronic obstructive pulmonary disease. AB - The aim of this study was to assess whether 2 dimensional echocardiography can provide reliable parameters to quantitatively estimate pulmonary hypertension (PH) in patients with chronic obstructive pulmonary disease. Twenty subjects, 16 males and 4 females, mean age 54.5 year +/- 4.92 were evaluated. Right ventricular dimensions were measured using subcostal 2- dimensional (2D) approach viz. right ventricular maximum short axis (Rv) and tricuspid annulus (TA). Free right ventricular anterior wall (AW) was measured by M-Mode. A 2D Index was calculated RV x TA + Aw and the same correlated with mean pulmonary artery pressure (r = 0.97). This appears to be a useful non-invasive method foe estimating PH in cases of COPD. PMID- 1512722 TI - Neurofibromatosis 2 (bilateral acoustic schwannomas). What is it? A review of literature and an update. PMID- 1512723 TI - The internal myxoedema syndrome of Eskamilla, Lisser and Shepherdson (a case report). PMID- 1512724 TI - Mesenchymal chondrosarcoma--a case report. AB - A Case of extraosseous mesenchymal chondrosarcoma occurring in the occipital region in a 26 year old male is being reported. The patient remained free from recurrence on any metastasis even after 2 years of the tumor resection. PMID- 1512725 TI - Fibromatosis of thyroid gland (a case report). AB - Fibromatosis of thyroid gland is a rare condition encountered in surgical practice. Clinically presenting as goitre, it is treated with near total thyroidectomy with good results. We had one such case under our care at the K.E.M. Hospital, Bombay. Rarity of this condition prompted us to publish the data, the literature is briefly reviewed. PMID- 1512726 TI - Persistent facial myokymia: a rare pathognomic physical sign of intrinsic brain stem lesions: report of 2 cases and review of literature. AB - Characteristically continuous facial myokymia is a pathognomonic, exceedingly rare physical sign of intrinsic brain-stem lesions e.g. multiple sclerosis (where the myokymia lasts only for a few months), pontine glioma (where it is unremitting for years). The physiopathogenesis is unclear. Electromyographic patterns are characteristic. Therapy and prognosis are related to the basic aetio pathological process. Only two out of 132 cases of intrinsic brain-stem lesions in the department of Neurosurgery, Seth G.s. Medical College, Bombay over a period of 3 decades, exemplify its rarity. These two cases are reported here and the relevant literature is reviewed. PMID- 1512727 TI - Bartter's syndrome: a neonatal presentation (a case report). PMID- 1512728 TI - Bizarre parosteal osteochondroma in the foot (a case report). AB - A rare case of a bizarre parosteal osteochondroma in the foot is presented. The tumour first described in 1983 by Nore et al is rare in any location and has to be differentiated from a juxta-cortical osteosarcoma and a benign osteosarcoma. Its differentiating characteristics are discussed. PMID- 1512729 TI - Renal angiomyolipoma (report of 2 cases). AB - Renal angiomyolipoma, a rare benign renal neoplasm constitutes less than 3 percent of all renal neoplasm. Two rare cases of renal angiomyolipoma were reported from the Department of Pathology, Dr. S.N. Medical College, Jodhpur in last fifteen years. Both were not associated with tuberous sclerosis. The relevant literature on the subject is reviewed. PMID- 1512730 TI - Bilateral pulmonary aneurysm in Behcet's disease (a case report). AB - While investigating a chest opacity in Behcet's disease possibility of pulmonary aneurysm should be considered. Contrast enhanced CT is a safe diagnostic method which is useful in confirming or excluding the presence of an aneurysm in such cases. We report here the first case of bilateral pulmonary aneurysms in Behcet's disease. PMID- 1512731 TI - Role of the family in drug abuse. AB - A simple random survey of 9863 population out of the total 70,000 population is one slum pocket of Bombay revealed drug dependence in 104 persons. Out of 104, 83.65% smoked 'brown sugar' 10.68% used cannabis and 5.77% opium. Most of the addicts (95.2%) belonged to large families. Family history of alcoholism and drug abuse was present in 41.35%. Parental deprivation was additional contributing factor in 30.7%. PMID- 1512732 TI - Comparative study of hemoglobin estimated by Drabkin's and Sahli's methods. AB - Hemoglobin was estimated by Sahli's and Drabkin's method in samples collected by finger prick and venepuncture. Statistical analysis revealed a significant difference in the hemoglobin values obtained by the two methods (P less than .01 & P less than .05 respectively). Sahli's method carried out by two different groups of workers in samples of blood collected by venepuncture showed statistically significant difference (P less than .001). This could be due to the inbuilt errors of Sahli's method including a subjective bias due to visual comparison. When same samples were subjected to Drabkin's method by the same group of workers no significant difference in the results were obtained (P less than .05). This is due to reliability of the Drabkins method. The aim of this comparative study of hemoglobin estimation by Sahli's and Drabkin's methods is to emphasize the sensitivity and reliability of Drabkin's over Sahli's and utility of Drabkin's method in undergraduate teaching schedule. PMID- 1512733 TI - An uncertain future: children of mentally ill parents. AB - Research reports the uncertain outcome of variables affecting the life of a child of an MI parent. Nurses must avoid stereotyping children before assessment; they are to be in the forefront in assessing self-care skills and deficits to guide planning individual interventions for children and MI parents. Long-term research theory-based interventions will enhance mental health in high-risk children and families. PMID- 1512734 TI - Empowering part-time nurses in the treatment of depressed inpatients. AB - 1. With the consistent number of part-time nurses in the workforce, hospitals would benefit by more actively integrating them into professional nursing practice. 2. Empowering part-time nurses by affording them the opportunity to provide primary care has the potential to effectively use part-time personnel, decrease the workload for full-time staff, offer more flexibility in scheduling, and result in savings for hospitals in terms of nursing recruitment and retention. 3. This program has successfully developed and implemented a model of primary nursing that places three part-time nurses on a team capable of handling two to three primary patients. The success of this model has been attributed to excellent communication, trust in one another's professional skills, and nursing expertise. PMID- 1512735 TI - Missile attack. PMID- 1512736 TI - The real purpose. PMID- 1512737 TI - Perceptions of seclusion: comparing patient and staff reactions. AB - Seclusion, or the use of locked, closely monitored containment, is widely used in psychiatric practice and is legally sanctioned. Involving humanitarian, ethical, and legal issues, seclusion poses dilemmas and raises questions for health-care professionals. Among those defending the practice, some would argue that it is used reluctantly and only as a last resort, whereas others consider it to be a positive therapeutic treatment modality, whether used alone or in conjunction with other treatments. Opponents of seclusion disagree, considering seclusion to be punitive, arbitrary, and geared toward serving the needs of other patients and staff. Although professionals have interpreted seclusion differently with regard to its function, efficacy, and impact, the vast majority of patients view it negatively. Wadeson and Carpenter (1976) found that individuals interviewed 1 year after seclusion still felt bitter about the experience; for many, that experience symbolized their entire psychiatric illness. PMID- 1512738 TI - Using a model to structure psychosocial nursing [corrected]. AB - 1. Specifying a model to guide research projects helps clarify the study, permits several investigators to work in a coordinated fashion on large projects, and facilitates comparisons across studies. 2. This model is composed of seven domains and indicates some of the hypothesized relationships between domains. Adapting the model to individual studies may result in a different number of domains and in the specification of other hypothesized relationships. 3. When possible, researchers should make use of minimum data sets to enhance the comprehensiveness and generalizability of their research. PMID- 1512739 TI - Codependency. PMID- 1512740 TI - The mental health review board: a new concept for difficult clients. AB - 1. The Mental Health Review Board concept is a hospital systems approach to the difficult client. Board membership varies with each case and includes representation from all areas of the hospital. 2. The Review Board deals with clients who have exhausted the system, are threatening or abusive to staff, and noncompliant with treatment recommendations. 3. The Review Board contract is the "final offer" for treatment and is without input from the client. Terms of the contract are nonegotiable. Noncompliance results in discharge and referral elsewhere. PMID- 1512741 TI - It's not the numbers that matter; it's what you do with them. PMID- 1512742 TI - Dental public health: new opportunities--new responsibilities. PMID- 1512744 TI - Supply decisions among dentists working within a fixed-fee system of dental care provision. AB - In Norway fees for dental treatment did not increase at the same rate as prices for other goods and services during the 1980s. The aim of this study was to examine how this decrease in fees in real terms has influenced dentists' work decisions with respect to supply of services. Data on characteristics of the dentist and the dental practice were collected for 1979, 1984, and 1986. The dependent variable was supply of dental services, measured as the number of patient care hours worked per annum. The hourly fee for dental care was equivalent to dentists hourly wage rate. Supply increased as fees decreased. This could be explained either as a response of the patient or the dentist to reduced fees. Although the data did not give conclusive evidence as to which effect was most important, the authors have put forward the view that the main effect was dentists' response to reduced fees. The main argument put in favor of this view is that dentists have an overall knowledge of the effect of a change in fees on their income. The impact of a change in fees is much greater on the provider who supplies the services to many individuals over a long period of time, than on an individual consumer who buys the services once or twice a year. It was concluded that, in the short run, a fixed-fee schedule may not be very effective in limiting costs for dental care. PMID- 1512743 TI - The prevalence of recurrent herpes labialis during an army hot weather exercise. AB - A survey was performed on 1,062 of 2,500 (42%) Army personnel participating in a desert training exercise at Fort Irwin, California, in September 1983. The prevalence of recurrent herpes labialis (RHL) and chapped lips was observed during the third week of a four-week training period. Complexion, sex, lip protectant use, age, and time spent outdoors were obtained by observation and interview. Recurrent herpes labialis was found in 46 subjects (4%). Stratified analysis and stepwise logistic regression were used to identify risk factors associated with RHL and to determine the prevalence odds ratios (POR). Risk factors with statistically significant associations with RHL were lip protectant use (POR = 0.19), chapped lips (POR = 2.87), being female (POR = 5.00), and light complexion (POR = 2.48). These findings strongly support the use of lip protectants during prolonged exposure to hot, dry climates as a prophylaxis against recurrent herpes labialis. Additional studies should focus on excitatory factors of RHL; and clinical trials of the efficacy of the lip protectants to protect against RHL and chapped lips should be undertaken. PMID- 1512745 TI - A profile of black and Hispanic subgroups' access to dental care: findings from the National Health Interview Survey. AB - This study examined which black and Hispanic minority subgroups were least likely to obtain dental care and why, based on logistic regression analyses of the 1986 National Health Interview Survey. Blacks and Hispanics were less apt to have private dental insurance coverage, to be knowledgeable about the purpose of fluoride, to have been to a dentist in the past year, and, when they did go, were more apt to have gone in response to symptoms rather than for preventive reasons, compared to whites. Logistic regression analyses for adults 18 years of age and older and for children and adolescents 2 to 17 years of age showed that the following individuals had the lowest probability of having been to a dentist in the past year: males, members of larger families, adults who were unemployed or in blue-collar jobs, those who lived in the South or nonmetropolitan areas, people who perceived their health to be fair or poor, and those with no private dental insurance. Mexican-Americans were least likely to have been to a dentist regardless of their income or education. In general, the findings confirmed the importance of dental insurance, as well as suggesting a need for more school based dental programs and public health clinic-based dental health education and outreach efforts for targeting minority children and adults. PMID- 1512746 TI - The need for toothpastes with lower than conventional fluoride concentrations for preschool-aged children. AB - Since 1945, when community water fluoridation was first implemented in the United States, not only has the procedure grown to cover more than half of the US population, but the development and use of other fluoride methods have expanded greatly. A concomitant, dramatic decrease has occurred in the caries prevalence of US school-aged children. Recent studies indicate, however, that the prevalence and, to a lesser extent, the intensity of dental fluorosis have increased in schoolchildren in both fluoridated and fluoride-deficient areas. Several studies show that young children inadvertently ingest sizable proportions of toothpaste during toothbrushing. Although ingestion of fluoride toothpastes by preschool aged children may not be the major contributor to the increase in fluorosis, the findings of at least four studies suggest that the use of fluoride toothpastes by young children is a risk factor. The direct dose-response relation between effectiveness and fluoride concentration of toothpastes is far from clear-cut and, at best, is weak. Thus, considering today's reduced risk of caries, it is timely to market fluoride toothpastes in the US with 400-500 ppm fluoride for preschool-aged children, who are still at risk for developing fluorosis, as has been done in several other countries. Dental public health authorities must work with toothpaste manufacturers, professional organizations, and regulatory agencies to facilitate the approval and marketing of such pediatric fluoride toothpastes. PMID- 1512747 TI - Factors affecting the ingestion of fluoride dentifrice by children. AB - Several factors affecting the amount of fluoride ingested during toothbrushing by 2- to 7-year-old children were investigated. The specific purpose of this study was to determine the contribution of age, the amount of dentifrice used, and rinsing after brushing to the variation in the ingestion of fluoride dentifrice. Four hundred and five children brushed their teeth in front of a portable sink. The tubes of dentifrice in gel (0.24% NaF) were weighed before and after use to determine the amount of toothpaste used. The fluoride content of the collected liquids was determined with a fluoride-ion-specific electrode. The amount of fluoride ingested was derived by determining the difference between the amounts used and recovered. The amount of dentifrice used, the age, and the rinsing habits, entered in a multiple regression model, explained up to 66 percent of the total variation in the amount of fluoride ingested. The amount of dentifrice used accounted by itself for 60 percent of the total variation. Therefore, these results indicate that the quantity of dentifrice used was the most important factor affecting the ingestion of fluoride through toothbrushing by young children. PMID- 1512748 TI - Comparison of number and mean charge between dental sealants and one-surface restorations. AB - An important concern of the insurer is how sealants, if a covered benefit, will affect the premium. Important factors that may have an influence on determining the premium include the decline in caries rate coupled with the long-term cost to an insurer for sealants vs one-surface restorations. In this study of more than 1 million dentally insured children (aged 5-15), the mean charge ($) for sealants and one-surface restorations was determined, along with the frequency of these procedures, by patient age. For this group of children, 43 percent of one-surface restorations occurred between ages 12-14, whereas 32 percent of the patients received sealants at either 7 or 8 years of age. States varied substantially in the number of sealants as a percentage of the number of restorations. Only three states had more sealants placed than one-surface, posterior restorations. Three states had an annual increase in the ratio of sealant to restoration charge, while 13 states had an annual decrease. With the exclusion of a few states with a minimum number of sealants and restorations in 1988, the highest ratio of the cost of sealants to the cost of one-surface restorations was observed in New York (.60) and New Jersey (.56) and the lowest observed in Kansas and Utah (.37). The ratios for both New York and New Jersey were lower in 1988 than in the previous two years. The ratio of the number of one-surface, posterior restorations to the population served was approximately the same for each NIDR region in the contiguous United States. Alaska and Hawaii had a higher proportion. PMID- 1512749 TI - Improving dental epidemiologic data collection with computers. AB - A computerized dental data recording system (DDRS) was developed for the New England Elder Dental Study to improve data quality and increase field staff efficiency. The DDRS displays video screens similar to traditional paper forms to record data on coronal and root caries, dentate and denture status, subacute bacterial endocarditis screening, gingival bleeding, calculus, and periodontal attachment level. DDRS provides facilities for date and exam-component time tracking, on-line contextual comments, random record retrieval, editing, data backup, and data output in various data formats. This study compared the DDRS with a paper-form system for data entry accuracy. Dental caries and periodontal disease measurement data from 38 subjects were recorded on paper forms and independently entered using DDRS. The DDRS identified 150 illogical data errors, 39 inconsistent data errors, 7 invalid data and 34 miscellaneous data errors. Four technicians with field experience using both paper forms and DDRS reported time savings using DDRS in the field. DDRS has the potential for additional time savings by minimizing the time for data coding, cleaning, and management. Results demonstrate that DDRS could improve the quality of oral epidemiologic data by mandating strict adherence to protocols, preventing errors, and increasing field efficiency. PMID- 1512750 TI - Opinions of dentists on the treatment of elderly patients in long-term care facilities. AB - The high prevalence of disorders in the mouths of elderly residents in long-term care (LTC) facilities suggests that the dental services available to the residents are inadequate. A questionnaire was sent to most of the dentists practicing in Vancouver (British Columbia) to solicit their opinions on treating older patients in LTC facilities, and a response was obtained from 334 (55%). It indicated that 19 percent of the respondents had treated old people within this context, although few of them felt they had been educated adequately for the service. Many reasons were offered to explain the small participation. Most respondents had never been asked to attend a facility. Many felt that it interfered with their practice and leisure, and they were concerned about the limited options available for treatment. Dentists who had attended facilities were motivated by a sense of professional or public responsibility, but they were uneasy about the limited options and about the inadequate space and equipment available. In general, the dentists were not interested in attending an institutionalized geriatric population, and they felt ill-prepared for the service. PMID- 1512751 TI - The John W. Knutson Distinguished Service Award in Dental Public Health--1991 Recipient: Philip E. Blackerby, Jr. PMID- 1512752 TI - Remarks by Dr. Philip E. Blackerby on receiving the John W. Knutson Distinguished Service Award in Dental Public Health. PMID- 1512753 TI - Photopheresis for scleroderma? No! PMID- 1512754 TI - Pancreatitis in systemic lupus erythematosus: still in search of a mechanism. AB - Pancreatitis in SLE remains an enigma and probably results from multiple pathogenetic mechanisms. However, cases of pancreatic thrombus formation remain few and far between, suggesting that APS is not the major cause of pancreatitis. Whether aPL contribute to pancreatic thrombus formation in rare patients needs to be demonstrated by antemortum arteriographic studies showing thrombus or vasculopathy. The postmortem pancreatic examination of patients who have died of the disseminated vasculopathy-coagulopathy syndrome remains problematic, because if thrombi are found, they may simply represent the endstage of multiple mechanisms, including hypotension, hypoxia, DIC, or TTP, rather than an aPL specific mechanism. PMID- 1512755 TI - Lactate in synovial effusions. PMID- 1512756 TI - Concordance between clinician and patient assessment of physical and mental health status. AB - The degree of concordance between clinicians' and patients' assessment of the patient's physical and mental functioning was examined in 166 consecutive eligible outpatients with rheumatoid arthritis (RA) using 4-category ordinal scales. The weighted kappa statistic was 0.39 for physical functioning and 0.30 for mental functioning, both indicating a fair degree of concordance. This disagreement differed in magnitude and direction depending on the level of disability present. We conclude that clinicians and their patients with RA often disagree in their assessment of the degree of physical and mental impairment that the patient experiences. These disagreements demonstrate the need for formal assessments of outcome and should be recognized and resolved when managing individual patients. PMID- 1512757 TI - Bucillamine inhibits T cell adhesion to human endothelial cells. AB - We investigated the ability of bucillamine [N-(2-mercapto-2-methyl-propionyl)-L cysteine] to prevent T cell adhesion to endothelial cells (EC) isolated from human umbilical vein. When EC were pretreated with bucillamine, T cell binding to the EC was suppressed in a dose dependent fashion. The T cells could bind preferentially to recombinant interferon-gamma (rIFN-gamma) treated EC compared with untreated EC. Bucillamine could also suppress T cell binding to rIFN-gamma treated EC as well as untreated EC. Addition of copper sulfate to bucillamine decreased significantly the percent T cell adhesion to the EC compared with bucillamine alone. The magnitude of inhibition by bucillamine and copper sulfate was similar in EC treated with rIFN-gamma as well as in untreated EC. H2O2 also inhibited the T cell binding to both untreated and rIFN-gamma treated EC. The inhibitory effects of bucillamine with or without copper sulfate on T cell binding to EC were abolished completely by catalase but not by superoxide dismutase. Our results suggest that hydrogen peroxide generated by bucillamine, with or without copper sulfate, inhibits T cell binding to EC. We believe, therefore, that bucillamine may suppress inflammation, such as that in rheumatoid synovitis, by reducing the emigration of chronic inflammatory cells from capillaries into tissue. PMID- 1512758 TI - Rheumatology function tests: grip strength, walking time, button test and questionnaires document and predict longterm morbidity and mortality in rheumatoid arthritis. AB - Four quantitative measures of functional status, grip strength, walking time, the button test, and a questionnaire regarding activities of daily living, were assessed nine years apart in 75 patients with rheumatoid arthritis (RA). After 9 years, 20 patients had died; none were lost to followup. Functional status had declined in more than 80% of patients according to each of the 4 measures, and patients with poor values at baseline were most likely to die over the next 5 years, as reported. We report that baseline values of these measures of functional status were predictive of values 9 years later. These measures may be regarded as "rheumatology function tests" to document and predict morbidity and mortality in RA over long periods. PMID- 1512759 TI - Synoviocyte derived granulocyte macrophage colony stimulating factor mediates the survival of human lymphocytes. AB - Synoviocytes have been shown to be effector cells capable of synthesizing and secreting a variety of cytokines and growth factors. We demonstrate here that synoviocyte derived conditioned medium has immunoregulatory properties as it enhances human peripheral blood lymphocyte survival in a dose dependent manner in vitro. The effect elicited by synoviocyte derived conditioned medium from patients with rheumatoid arthritis (RA) was greater than that induced by synoviocyte derived conditioned medium from patients with osteoarthritis. Granulocyte-macrophage colony stimulating factor (GM-CSF) was found in synoviocyte derived conditioned medium with significantly higher levels present in synoviocyte derived conditioned medium from patients with RA. Recombinant human GM-CSF induced survival of human lymphocytes in vitro and a monoclonal antibody to human GM-CSF fully abrogated synoviocyte derived conditioned medium induced survival. Our results demonstrate that synoviocyte derived GM-CSF may be important in the retention of lymphocytes, which is a central pathological characteristic of the rheumatoid joint. PMID- 1512760 TI - Asialylated IgG in the serum and synovial fluid of patients with rheumatoid arthritis. AB - A novel enzyme linked immunosorbent assay has been developed that detects an asialylation change in the IgG molecules from patients with rheumatoid arthritis (RA) by the binding of biotinylated RCA 1 (ricin) to capture IgG. Elevated levels of asialylated IgG were detected in paired serum and synovial fluids (SF) of patients with RA. When compared with healthy controls, particularly in the SF (p less than 0.05) correlations of the asialylation change were found in paired samples (p less than 0.01) and between asialylated IgG and rheumatoid factors (p less than 0.01), C-reactive protein (p less than 0.02) and the Lee and Ritchie indices p less than 0.02 and 0.05, respectively. We found the proportion of asialylated IgG was higher in DR4 positive patients, indicating a possible association of these individuals to a sialyl transferase abnormality. PMID- 1512761 TI - Possible mechanisms of gastroduodenal mucosal damage in volunteers treated with nonsteroidal antiinflammatory drugs--the usefulness of prodrugs. AB - A controlled double blind study on the incidence of nonsteroidal antiinflammatory drug (NSAID) gastropathy was performed in 29 healthy volunteers administered diclofenac Na (10 subjects) or a prodrug (loxoprofen Na in 10 subjects and proglumetacin maleate in 9 subjects). The incidence of NSAID gastropathy was significantly lower in the subjects administered the prodrugs than in those administered diclofenac Na (p less than 0.05), which suggested the clinical usefulness of the prodrugs. PMID- 1512762 TI - Course of antiphospholipid antibodies in patients with primary antiphospholipid syndrome before, during and after pregnancy treated with low dose aspirin. Relationship of antibody levels to outcome in 7 patients. AB - We studied 7 patients with primary antiphospholipid syndrome (APS), who had had, between them, 28 fetal losses in 30 pregnancies. The 2 successful pregnancies had occurred 14 years previously. The patients had been followed for a mean of 20.5 months with a mean of 6.4 determinations of antiphospholipid antibodies (aPL) before becoming pregnant again. Serial determinations of aPL continued to be done throughout pregnancy. Patients were treated with low dose aspirin only except for one who had prednisone added at the time of an impending abortion. Five patients had successful outcomes and 2 had stillbirths. In the patients who had pregnancy loss, as well as in those who had other obstetric incidents there were abrupt changes in IgG, but not in IgM, levels. Levels of IgG aPL in patients with successful outcomes tended either to decrease gradually or to remain stable throughout. We conclude that patients with primary APS who had repeatedly unsuccessful pregnancies may show changes in their IgG levels during pregnancy that could indicate impending morbidity. In some of them low dose aspirin may prevent pregnancy loss. PMID- 1512763 TI - The differing patterns of interstitial lung involvement in connective tissue diseases. AB - Connective tissue disorders (CTD) have a relatively high incidence of pulmonary complications but their delineation has been hampered by difficulties inherent in the diagnostic techniques. One fresh approach to this problem is based on a clustering method that uses data from 8 separate investigations to cluster the patients into 4 distinctly separate categories representing normal nonsmoker, normal smokers, those with active interstitial lung disease and those with bronchiolitis. Using this method, a large group of patients with CTD have been examined to assess the nature and extent of their pulmonary complications. Subjects in the first cluster had a normal test profile across all variables, and included no current active smokers. The normal smoking cluster contained only smokers who had a high total lavage cell number with a relative increase in macrophages and a decrease in lymphocytes. In this group, all respiratory variables were normal with the exception of a mildly depressed DLCO, also known to be associated with smoking. The general characteristics of the active interstitial lung disease cluster was a markedly depressed DLCO indicating impaired gas exchange, and elevated gallium index, bronchoalveolar lavage (BAL) cell number and neutrophil and lymphocyte percentages, all indicating an active inflammatory process. However more careful analysis of this group suggested the presence of 2 subgroups, one with a lymphocytic alveolitis, and another with a neutrophilic alveolitis. The bronchiolitis cluster characteristics were a markedly depressed maximal mid expiratory flow rate and raised BAL lymphocyte percentage and gallium index. The distribution of patients within the cluster groupings suggested that Sjogren's syndrome, often an accompaniment of other CTD, is most frequently associated with pulmonary disease.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1512764 TI - Disease patterns of patients with systemic lupus erythematosus as shown by application of factor analysis. AB - Clinical and laboratory test data of 77 patients with systemic lupus erythematosus (SLE) were evaluated by factor analysis. Six factors representing disease patterns were extracted: cutaneous symptoms of alopecia, malar rash, rash and photosensitivity; renal involvement; the anticoagulant syndrome of phlebitis and partial thromboplastic time inversely related to platelet count; lymphopenia; viral or fibromyalgia symptoms of headache, nervousness, joint and muscle pain; and serology of anti-DNA antibodies and complement inversely related. Application of factor analysis reveals various clinical presentations of SLE. PMID- 1512765 TI - Soluble interleukin 2 receptors in polymyalgia rheumatica/giant cell arteritis. Clinical and laboratory correlations. AB - Serum levels of soluble interleukin 2 receptors (sIL-2R) were measured in 21 patients with polymyalgia rheumatica (PMR)/giant cell arteritis (GCA) prior to steroid treatment. These levels were significantly elevated in patients with PMR/GCA compared with healthy controls (p = 0.002). A significantly longer duration of morning stiffness (p = 0.005) was observed in patients with a high concentration of sIL-2R. A significant correlation was observed at diagnosis between sIL-2R and erythrocyte sedimentation rate (ESR) (p = 0.01) and between ESR and C-reactive protein (CRP) (p = 0.005). We investigated prospectively a group of 10 patients over a period of 6 months of prednisone therapy. At the end of the study sIL-2R levels fell significantly compared to pretreatment values (p = 0.02), but remained significantly higher compared to controls (p = 0.02). ESR and CRP values also fell significantly compared to pretreatment levels (p = 0.0001 in both cases). We observed a significant correlation between the decrease in ESR values and the decrease in sIL-2R and CRP levels after 6 weeks (p = 0.01 in both cases) and after 6 months of therapy (p = 0.002 and p = 0.05). sIL-2R may be considered a useful serologic marker for monitoring response to steroid therapy in patients with PMR/GCA. This laboratory variable correlated more closely with ESR than with CRP. The presence of elevated levels of sIL-2R is likely to reflect T cell activation occurring in PMR/GCA. T lymphocyte activation persisted after 6 months of steroid therapy, despite rapid and continuous control of disease manifestations. PMID- 1512766 TI - Determinants of synovial fluid lactate concentration. AB - The resting intraarticular pressure and the type of arthropathy [rheumatoid arthritis (RA) or non-RA] have been examined for their importance as determinants of synovial fluid (SF) lactate concentration in patients with knee effusions. SF lactate concentration was higher in RA than in non-RA knees. This difference was not related to the resting intraarticular pressure at the time of sampling. After drainage of SF and saline lavage of the joint, the rate of increase of lactate in a fixed volume of intraarticular saline was examined under resting conditions. The rate of increase of the lactate concentration was significantly greater in RA joints. It is most likely that SF lactate concentration under resting conditions will reflect the lactate concentration during the preceding period of activity which, in turn, is probably a composite function of the extent of synovial hypoxia due to hypoperfusion and the type of arthropathy. PMID- 1512767 TI - Synovial fluid crystals derived from erythrocyte degradation products. AB - We report 5 patients with bloody effusions containing crystals not previously reported to occur in synovial fluid. In one patient, rectangular hemoglobin-like crystals were found inside red cells previously observed elsewhere. In the other 4 cases, golden brown rhomboid crystals with positive elongation appeared to be hematoidin, a degradation production of hemoglobin, which has been found in nonarticular areas of old hemorrhage. In one patient, hematoidin crystals were identified lying in macrophage vacuoles. Both types of crystals are potential sources of confusion with known pathogenic crystals. PMID- 1512768 TI - Patients with rheumatoid arthritis are more tender than those with psoriatic arthritis. AB - Articular and nonarticular tenderness was examined in 51 patients with rheumatoid arthritis (RA) and 50 patients with psoriatic arthritis (PsA) by scored palpation and dolorimeter readings. Fifty-seven percent of patients with RA had 10 or more tender fibrositic points vs 24% of patients with PsA (p = 0.0008). Thresholds of tenderness measured by dolorimetry of 6 fibrositic point sites were 3.97 (1.99) [mean (SD)] for RA vs 5.95 (2.28) for PsA (p less than 0.0001). Thresholds over actively inflamed joints were 4.19 (1.53) for RA vs 6.78 (2.55) for PsA (p less than 0.0001). In both RA and PsA, fibrositic sites were more tender than actively inflamed joints (p less than 0.0001). Nonarticular control sites were also more tender in subjects with RA with dolorimeter thresholds at 5.99 (1.96) in RA vs 7.58 (1.60) in PsA (p less than 0.0001). These data demonstrate that actively inflamed joints, fibrositic and control nonarticular sites were all more tender in patients with RA than PsA. Both groups were similar in their disease duration and clinical assessments of joint inflammation and damage. We suggest that there may be a disease specific diffuse increase in tenderness in patients with RA, which is not related to joint inflammation. Similarly, the severity of articular inflammation may be underestimated in subjects with PsA. PMID- 1512769 TI - Thyroid function in patients with fibromyalgia syndrome. AB - Thyroid function was tested in 13 female patients with primary fibromyalgia syndrome (FS) and 10 healthy age matched controls by intravenous injection of 400 micrograms thyrotropin-releasing hormone (TRH). Basal thyroid hormone levels of both groups were in the normal range. However, patients with primary FS responded with a significantly lower secretion of thyrotropin and thyroid hormones to TRH, within an observation period of 2 h, and reacted with a significantly higher increase of prolactin. Total and free serum calcium and calcitonin levels were significantly lower in patients with primary FS, while both groups exhibited parathyroid hormone levels in the normal range. PMID- 1512770 TI - Pancreatitis related to antiphospholipid antibody syndrome in a patient with systemic lupus erythematosus. AB - A 39-year-old woman was admitted with abdominal pain and dyspnea, and a diagnosis of systemic lupus erythematosus with renal involvement was established. Laboratory tests revealed highly elevated anticardiolipin antibody, thrombocytopenia and false positive VDRL. Generalized thrombus formation and Libman-Sacks endocarditis were found at postmortem examination. The pancreas showed chronic inflammation with thrombi in pancreatic arteries, but no vasculitic change was observed. Lowering of pancreatic blood flow because of arterial thrombi was a possible cause of pancreatitis in this patient. The spectrum of antiphospholipid antibody associated diseases may be extended to include pancreatitis as a thrombotic complication. PMID- 1512771 TI - Splenectomy as treatment for nonhealing soft tissue defect after total knee arthroplasty in a patient with Felty's syndrome. AB - We describe the apparent remarkable effect of splenectomy on wound healing in a patient with rheumatoid arthritis and Felty's syndrome. The patient had previously undergone a knee replacement with 4 months of failure of the surgical wound site to heal or close. The wound, which had broken down and dehisced on 3 separate occasions after plastic surgical attempts at closure, healed cleanly and without recurrence within 3 weeks of splenectomy and plastic repair at the same operation. PMID- 1512772 TI - Development of systemic lupus erythematosus after total resection of a thymoma and the adjacent thymic gland. AB - We describe a woman with systemic lupus erythematosus presenting with nephropathy after the complete resection of a thymoma and the adjacent thymic gland. The woman showed no symptoms of autoimmune disorders or nephropathy at operation. One year later, however, she noticed arthralgia, and laboratory examination showed mild proteinuria, leukopenia, a high level of serum antinuclear antibody (1:1280), anti-dsDNA antibody, and a low level of complement. Renal biopsy showed focal necrotizing glomerular lesions, suggestive of lupus involvement. The pathogenesis of lupus erythematosus in our case is briefly discussed in relation to preceding thymoma and its resection. PMID- 1512773 TI - Malignant angioendotheliomatosis mimicking systemic necrotizing vasculitis. AB - Malignant angioendotheliomatosis is a rare disease characterized by an intravascular proliferation of atypical mononuclear cells. Manifestations result from occlusion of small blood vessels. Multiple organ systems are involved and the clinical presentation resembles a systemic necrotizing vasculitis with skin and central nervous system most commonly involved. The clinical course is characterized by progressive organ failure with death usually within 2 years after presentation. Based on its assumed origin as an intravascular lymphoma, patients may respond to chemotherapy. PMID- 1512774 TI - Bronchiolitis obliterans organizing pneumonia and scleroderma. AB - Pulmonary involvement in scleroderma is characterized by interstitial fibrosis and pulmonary hypertension. Although bronchiolitis obliterans organizing pneumonia (BOOP) may be associated with a variety of connective tissue diseases and their treatment, there are only rare reports of bronchiolitis associated with scleroderma. We describe 2 patients with scleroderma and rapidly evolving pulmonary infiltrates, which upon biopsy showed histologic findings of BOOP. Each patient had severe restrictive lung disease and markedly diminished diffusion capacity. Treatment with high dose prednisone showed a good response in one patient. The rapid course of pulmonary findings in these patients differs from the usual course of pulmonary fibrosis in scleroderma. Although BOOP is a rare finding in scleroderma, our findings suggest that rapid pulmonary decompensation or atypical findings for pulmonary fibrosis should prompt consideration for an open lung biopsy. Finding a potentially steroid responsive disorder in an otherwise steroid unresponsive disorder has important clinical implications. PMID- 1512775 TI - Atypical eosinophilic fasciitis localized to the hands and feet: a report of four cases. AB - We describe 4 patients who had episodic localized swelling of an extremity, 2 of the hand and 2 of the foot, in combination with peripheral eosinophilia and a biopsy characteristic of eosinophilic fasciitis (EF). Surgical excision produced marked improvement in the patients' symptoms. Whether these patients, despite a characteristic biopsy, can be included in the spectrum of EF remains uncertain. PMID- 1512776 TI - The association of idiopathic retroperitoneal fibrosis and ankylosing spondylitis. PMID- 1512777 TI - Scleroderma with bilateral synovial fistulae. AB - Synovial fistulae developed in an elderly man with rapidly progressive scleroderma. We describe this case and review the literature on synovial fistulae. PMID- 1512778 TI - Hypertrophic osteoarthropathy and thyroid cancer. AB - We describe a case of aggressive undifferentiated thyroid cancer associated with rapidly evolving hypertrophic osteoarthropathy (HOA) that developed at the time of pulmonary dissemination of the thyroid neoplasm. The syndrome appeared to be paraneoplastic, possibly due to a substance normally cleared by the lungs. PMID- 1512779 TI - Systemic manifestations in granulomatous mastitis. PMID- 1512780 TI - Can liver test abnormalities in patients with rheumatoid arthritis be predicted by clinical symptoms? PMID- 1512781 TI - Asplenia in a patient with systemic lupus erythematosus and antiphospholipid antibodies. PMID- 1512782 TI - Hypersensitivity angiitis in an adult with rubella infection. PMID- 1512783 TI - Birth-cohort analysis: a technique come of age. PMID- 1512784 TI - Environmental tobacco smoke: the price of scientific certainty. PMID- 1512785 TI - Skin cancer concerns. PMID- 1512786 TI - Sun plays havoc with light skin down under. PMID- 1512787 TI - Dangers seen in increased treatment of elderly. PMID- 1512788 TI - Breast cancer treatment successful regardless of age. PMID- 1512789 TI - Older Americans are priority in cancer research. PMID- 1512790 TI - Non-toxic drug being tested to treat cancer and anemias. PMID- 1512791 TI - Implications of birth cohort patterns in interpreting trends in breast cancer rates. AB - BACKGROUND: Most investigations of trends in cancer rates are based on a cross sectional approach, i.e., an examination of trends in rates by year of diagnosis or death. When there are longitudinal effects (i.e., trends in rates with successive birth cohorts), interpretation of cross-sectional trends can be misleading. Based on cross-sectional comparisons, U.S. breast cancer mortality rates have been reported to be decreasing over the last 20 years in younger women but to be increasing during the same period in older women. PURPOSE: To examine the impact of longitudinal effects on the divergence of cross-sectional trends in breast cancer mortality with age, we examined breast cancer mortality rates from 1969 to 1988 by birth cohort for White women in the United States. METHODS: By using a novel, nonparametric, permutational method to analyze 2-year, age specific mortality rates for women aged 30-89 years, we identified trends in rates with successive birth cohorts. RESULTS: The divergence in trends with age is shown to be consistent with an increase in breast cancer risk with successive birth cohorts from 1900 to 1916 and with a decrease in breast cancer risk with successive birth cohorts beginning around 1926. CONCLUSION: Longitudinal effects have a significant impact on cross-sectional trends in breast cancer mortality. IMPLICATIONS: Continuation of the birth cohort trend in younger women, which could correspond to changes in reproductive patterns accompanying the "baby boom," would result in decreasing cross-sectional trends in women 60-69 years of age over the next decade and in women 70-79 years of age in the subsequent decade. Longitudinal effects must be taken into consideration when monitoring and evaluating the effects of early detection, treatment, and intervention programs using national rates. PMID- 1512792 TI - Peanut lectin: a mitogen for normal human colonic epithelium and human HT29 colorectal cancer cells. AB - BACKGROUND: The protein peanut agglutinin (PNA) is a galactose-binding lectin whose receptor, the Thomsen-Friedenreich (TF) blood-group antigen, shows increased expression in hyperplastic and neoplastic colonic epithelium. PURPOSE: Our hypothesis was that, under these conditions, increased lectin receptors could interact with dietary lectins, which would act as tumor promoters by stimulating cell proliferation. This study was designed to confirm whether active PNA is recoverable from feces after ingestion of peanuts and to assess the mitogenic effect of PNA on proliferation of epithelial cells in the colon. METHODS: Peanut lectin was extracted from feces by lactose-agarose affinity chromatography and was assayed for hemagglutinating activity. Cultured explants of histologically normal biopsy specimens of colonic mucosa from 31 patients were examined. Crypt cell production rate and incorporation of [3H]N-acetylglucosamine into mucin were assessed as indicators of proliferative and metabolic responses to PNA. In addition, we evaluated the separate and combined effects of PNA and epidermal growth factor (EGF) on cell proliferation in human HT29 colorectal cancer cells, by using tritiated thymidine incorporation and cell counts. RESULTS: Peanut lectin extracted from feces showed hemagglutinating activity toward desialylated red blood cells similar to that of a lectin preparation extracted from raw peanuts. Evaluation of biopsy specimens of normal colonic mucosa demonstrated that PNA at a concentration of 25 micrograms/mL caused statistically significant increases in crypt cell production (31% [mean] +/- 5% [SD]; P = .00005) and mucus synthesis (77% +/- 12%; P less than .000001). At 7.5-100 micrograms/mL, PNA was mitogenic for the HT29 colorectal cancer cell line. At 25 micrograms/mL, PNA alone produced a statistically significant increase in thymidine incorporation (44% [mean] +/- 3.7% [SD]; P = .002). For PNA in combination with EGF at 100 pg/mL, the increase was significantly greater (222% +/- 11.2%) than that for EGF alone (57% +/- 5%; P = .003). CONCLUSIONS: These results suggest that expression of the PNA receptor, TF antigen, by hyperplastic or neoplastic colonic epithelium may affect cell proliferation. IMPLICATIONS: It is possible that dietary lectins such as PNA, which bind to the TF antigen, promote cell proliferation and thus cancerous growth, while galactose-containing vegetable fiber would inhibit this effect by competing for binding by these lectins. PMID- 1512793 TI - Environmental tobacco smoke and lung cancer risk in nonsmoking women. AB - BACKGROUND: Exposure to environmental tobacco smoke (passive smoking) has been suggested to be a cause of lung cancer, although early epidemiologic studies have produced inconsistent results. PURPOSE: We conducted an epidemiologic case control study to assess the relationship between exposure to environmental tobacco smoke and lung cancer risk among women who have never smoked (i.e., having smoked for a total of less than 6 months or having smoked less than 100 cigarettes in their lifetimes). METHODS: Case patients (n = 210) were women with histologically confirmed primary carcinomas of the lung who were lifetime nonsmokers. They were identified through hospital tumor registries and the Florida Cancer Data System of the Statewide Cancer Registry. Community-based control women (n = 301) were also lifetime nonsmokers and were identified through random-digit dialing. Details on childhood and adulthood exposures to environmental tobacco smoke were ascertained through interviews with the study participants themselves or with surrogate respondents. Risks were calculated in terms of smoke-years, defined as the sum of the reported years of exposure to cigarette smoke from each smoker in the household. RESULTS: The risk of lung cancer more than doubled for women who reported 40 or more smoke-years of household exposure during adulthood (odds ratio [OR] = 2.4; 95% confidence interval [CI] = 1.1-5.3) or 22 or more smoke-years of exposure during childhood and adolescence (OR = 2.4; 95% CI = 1.1-5.4). Risks were highest for non adenocarcinoma lung cancers, although modest elevations in risk were also observed for adenocarcinomas. When a surrogate respondent other than the patient's husband provided information on exposure, the risk estimates were considerably lower. CONCLUSION: These findings suggest that long-term exposure to environmental tobacco smoke increases the risk of lung cancer in women who have never smoked. PMID- 1512794 TI - Second cancers in patients with chronic lymphocytic leukemia. AB - BACKGROUND: Reports to date have provided widely divergent estimates of the risk of second malignant neoplasms in patients with chronic lymphocytic leukemia (CLL), ranging from cancer deficits to excesses of twofold to threefold. PURPOSE: Our purpose was to estimate the risk of second primary cancers following CLL, utilizing population-based tumor registries, and to determine whether site specific excesses might be associated with type of initial treatment for CLL. METHODS: We analyzed data for 9456 patients diagnosed with CLL as a first primary cancer between 1973 and 1988, who were reported to one of nine tumor registries participating in the National Cancer Institute's Surveillance, Epidemiology, and End Results (SEER) Program and who survived 2 or more months. SEER files were searched for invasive primary malignancies that developed at least 2 months after the initial CLL diagnosis. RESULTS: Compared with the general population, CLL patients demonstrated a significantly increased risk of developing all second cancers (840 observed; observed-to-expected ratio [O/E] = 1.28; 95% confidence interval [CI] = 1.19-1.37). Significant excesses were noted for cancers of the lung (O/E = 1.90), brain (O/E = 1.98), and eye (intraocular melanoma) (O/E = 3.97) as well as malignant melanoma (O/E = 2.79) and Hodgkin's disease (O/E = 7.69). Cancer risk, which did not vary according to initial treatment category, was also constant across all time intervals after CLL diagnosis. CONCLUSION: CLL patients are at a significantly increased risk of developing a second malignant neoplasm. The pattern of cancer excesses suggests a susceptibility state permitting the development of selected second malignancies in patients with CLL, perhaps because of shared etiologic factors, immunologic impairment, and/or other influences. Although our results do not suggest a strong treatment effect, more detailed studies of second tumors in CLL are needed to investigate the role of radiation therapy and chemotherapy. PMID- 1512796 TI - Antagonism by suramin of the growth-inhibitory effect of hydroxytamoxifen and doxorubicin in human MCF-7 breast cancer cells. PMID- 1512795 TI - Increasing incidence of cutaneous melanoma in Queensland, Australia. AB - BACKGROUND: Queensland, Australia, had the world's highest incidence rates of invasive cutaneous melanoma in the 1970s. PURPOSE: The purpose of this study was to monitor trends in melanoma incidence in Queensland. METHODS: We studied two time periods in which ascertainment was comparable. RESULTS: In the 7.5 years up to 1987, the incidence of invasive melanoma in Queensland increased by more than one half in women (to 42.89 per 100,000) and more than doubled in men (to 55.81 per 100,000), with the most dramatic increase seen in men over age 50 years. This higher increase in men is a reversal of the previously higher rates in women. In Queensland, cumulative risks of total cutaneous melanoma (in persons aged 0-74 years), including preinvasive melanoma, have increased to one in 14 in men and to one in 17 in women. There were large increases in age-standardized incidence rates of thin lesions (less than 0.75 mm) in both sexes but not of in situ lesions, and there were also increases in thicker lesions, especially on the backs of males. CONCLUSIONS: Although increased awareness and earlier diagnosis appear to have accompanied increased incidence, increased exposure to solar UV radiation during the past 50 years appears to be the most likely explanation for the rise in incidence rates. IMPLICATIONS: A better understanding is needed of the causes of melanoma and of the complex relationships between constitutional factors, ambient UV radiation, and sun-exposure behavior. PMID- 1512797 TI - Melanoma risk and multiple moles. PMID- 1512798 TI - Deaf culture and alcohol and substance abuse. AB - Alcohol and substance abuse problems are now of concern among persons who are deaf. The problems of cultural influence, prevalence of the problem, and factors contributing to isolation and denial are addressed in this article. In addition, the issues of accessibility and service delivery are explored. Current programs that are accessible and provide alcohol and substance abuse recovery are identified. PMID- 1512799 TI - Psychoanalysis of a man with active alcoholism. AB - Psychoanalysis of a man with active alcoholism, who is able to resume recreational drinking, has never been described. Mr. A. began treatment in denial of his alcoholism. Analysis demonstrated an underlying splitting between his experiencing and observing ego. His analyst received a projection of his observing ego, the part that was worried about his drinking. Because this split was resolved within a therapeutic alliance, Mr. A. decided that he had been attacking and punishing himself with alcohol, and he elected to abstain from alcohol entirely. The first key event that lead up to this dramatic decision was a sense that his analyst was a separate person. The second, arriving for discussion within the analysis through a dream, was his conviction that he would have to choose either to continue to drink with loss of control at the cost of his analysis or that he would have to choose to continue analysis at the expense of having to stop drinking. Mr. A. then came to feel that his analyst was attacking and punishing him with a fee increase. After 15 months of complete abstinence, Mr. A. found that he could drink with rare symptoms, but he still felt saddled with an abusive analyst. Mr. A.'s rages about the fee came up most commonly right after weekend or vacation breaks in the analysis. But the interpretation of these rages as related to missing me were contemptuously regarded as attempts to force him into my psychoanalytic schema rather than regarding his experience as valid. There was a dramatic shift of our alliance when Mr. A. was given complete control over the fee. I was freed to interpret and reconstruct the underlying early relationship with his parents. The final part of this article describes Mr. A.'s working-through process, which stabilized his sense of autonomy and which reconstructed his early relationship with his parents. Mr. A. became convinced that it was up to him exactly how, when, and how much to drink. Drinking too much led to consequences that he chose not to endure. PMID- 1512800 TI - Two cases of clonidine abuse/dependence in methadone-maintained patients. AB - Clonidine has been used to assist opiate detoxification in the past 10 years. This substance is known to have multiple effects on the central nervous system and to cause withdrawal symptoms when stopped abruptly. The combination of these two effects could result in clonidine having a potential for abuse. Two cases of clonidine abuse/dependence in methadone-maintained patients are presented. Nonmedical use of clonidine in opioid-dependent persons has never been evaluated. PMID- 1512801 TI - Habituation to zipeprol hydrochloride during pregnancy. AB - Zipeprol hydrochloride is a synthetic antitussive agent that has shown little evidence of addictive potential in animal studies. Despite this, several reports of abuse and abuse-related over-dosage have been published. Abuse of this drug has now become a problem in the United States-Mexico border region. We report the specific case of a pregnant woman habituated to zipeprol without evidence of other drug abuse and an abstinence syndrome observed in her newborn infant. PMID- 1512802 TI - Use of the Dementia Rating Scale as a test for neuropsychological dysfunction in HIV-positive i.v. drug abusers. AB - Intravenous drug abusers (IVDAs) represent an increasing proportion of the HIV epidemic. Forty-three IVDA's (22 HIV-negative, 21 HIV-positive) were studied using the Mattis Dementia Rating Scale (DRS). All subjects had used intravenous heroin, but reported that they were drug-free at the time of testing. HIV positive subjects were predominantly symptomatic and were dichotomized into AIDS and non-AIDS groups. All subjects with abnormal DRS scores were HIV-positive (57% of all HIV-positives). All HIV-negative subjects had normal DRS scores while 43% of the positive group obtained such scores. The DRS reliably identifies neuropsychological impairment, and may be a useful screening tool in this population. PMID- 1512803 TI - Maternal bereavement in the perinatal substance abuser. AB - Maternal bereavement has been reported in involuntary perinatal loss and voluntary custody relinquishment. Since child custody loss is common among childbearing chemically dependent women, maternal bereavement was investigated in a small pilot sample of obstetric substance abusers. Findings suggest that grief in anticipation of possible postnatal custody loss is common. Unresolved grief from previous custody loss was also common. Clinical features, treatment considerations, and public health concerns are discussed. PMID- 1512804 TI - Relapse prevention and the need for brief social interventions. PMID- 1512805 TI - Methadone dosage, program policies, and heroin use among methadone patients. PMID- 1512806 TI - Altered states of consciousness therapy. A missing component in alcohol and drug rehabilitation treatment. PMID- 1512807 TI - The effectiveness of treatment for substance abuse. Reasons for optimism. AB - Reviews of treatment research have sometimes drawn gloomy conclusions which clash with the experience of clinicians. Yet the same literature provides reasons for optimism about the future of substance abuse treatment. There are treatment strategies with encouraging evidence of effectiveness that are only beginning to be applied in practice. Furthermore, research is clarifying the mechanisms and reasons for successful treatment, pointing to factors to be emphasized in therapy. Approaches that yield even short-term advantages can promote more rapid recovery, and may provide clues for how to prevent relapse. In difficult economic times, hope is also provided by evidence that even relatively brief treatment can be substantially more effective than none at all. Recent evidence also supports the importance of matching clients to alternative treatment strategies. To the extent that practitioners can keep abreast of such developments and adjust their clinical work accordingly, there is reason to believe that the effectiveness of substance abuse treatment can be greatly increased. PMID- 1512808 TI - Prolonged toxicity with intermediate syndrome after combined parathion and methyl parathion poisoning. AB - A prolonged type of organophosphate toxicity, previously characterized as the Intermediate Syndrome, has been recognized in 6 out of 7 prospectively studied patients poisoned by insecticide containing parathion and methyl parathion in equal proportions. The clinical characteristics included respiratory paresis, weakness in the territories of several motor cranial nerves, neck flexors and proximal limb muscles, and depressed tendon reflexes, all lasting for several days or weeks. Electromyography in the early stages disclosed diverse types of impaired neuromuscular transmission. EMG normalization preceded clinical recovery. Severe plasma butyrylcholinesterase and erythrocyte acetylcholinesterase inhibition persisted along with the occurrence of Intermediate Syndrome-related symptoms. We conclude that combined parathion and methyl parathion poisoning is more likely to induce Intermediate Syndrome than parathion poisoning alone. The mechanisms underlying this difference remain obscure. The Intermediate Syndrome shows clinical and electromyographic hallmarks of combined postsynaptic impairment of neuromuscular transmission. PMID- 1512809 TI - In vitro skin irritation assays: relevance to human skin. PMID- 1512810 TI - The adsorption of isopropanol and acetone by activated charcoal. AB - This study was performed to determine the adsorption of isopropanol and acetone by activated charcoal over a range of charcoal:solvent ratios. The charcoal binding of isopropanol was studied in both hydrochloric acid and water solutions, while acetone was analyzed in water. Gram ratios of charcoal to solvent ranged from 1:1 to 20:1. After the addition of charcoal the solution was agitated and centrifuged. The supernatant was then analyzed by gas chromatography. Each increment in charcoal dose increased the percent adsorption of both isopropanol and acetone. At the 20:1 ratio 87-92% of the solvent was bound by activated charcoal. In vivo study is needed to determine if activated charcoal therapy can shorten the half-life of isopropanol and acetone and decrease the duration of supportive care needed following ingestions of these solvents. PMID- 1512811 TI - Duration of QRS disturbances after severe tricyclic antidepressant intoxication. AB - While the clinical toxicity of tricyclic antidepressants, particularly the development of seizures and arrhythmias, has been strongly correlated with a QRS interval of greater than or equal to 100 msec on electrocardiography, the resolution pattern of QRS abnormalities remains poorly defined. We prospectively monitored 22 consecutive patients who were referred to a regional poison center after a tricyclic antidepressant ingestion associated with a QRS interval of greater than 100 msec. An ECG was obtained every 6-8 h in all patients until the QRS interval was less than 100 msec. Among enrolled patients the mean maximal QRS interval was 145 msec. Ten patients (45.5%) developed seizures while 6 (27%) developed cardiac arrhythmias. The time from ingestion to the last ECG demonstrating a widened QRS interval was a median 12.3 h (range 1-70 h); the time from ingestion to the first ECG with a QRS less than 100 msec was a median 19.3 h (range 3-78 h). No patients developed seizures or life-threatening cardiac arrhythmias after the QRS interval was less than 100 msec. Ten patients received sodium bicarbonate while 12 did not. There were no significant differences in the duration of QRS widening between the two groups. These data suggest that the typical period of QRS prolongation after severe tricyclic antidepressant ingestion is 12-18 h but may be as long 3 d. The factors which determine the duration of QRS widening are unclear. Sodium bicarbonate may not reduce the total duration of QRS disturbances. PMID- 1512812 TI - Cardiac monitoring during medical management of cocaine body packers. AB - The cardiac risk of cocaine body packing was studied by means of continuous ECG monitoring in 13 cocaine body-packers during spontaneous elimination. The packages were all well manufactured bundles (McCarron type 2) not susceptible to spontaneous breakage. At the beginning of the Holter study, packages were still present in the bowel of twelve patients (range: 2 to 196). The mean time of Holter recording was 46 h (range 16 h to 75 h). Ten patients eliminated all their packages during the time of Holter recording. No ECG modifications were recorded for all of the patients in regard to usually admitted standard requirements of the American Heart Association. While initial cardiac frequencies were within the normal range, a significant decrease of pulse rates was associated with the elimination of bundles. We conclude that the McCarron type 2 cocaine body-packers are not in impending danger of cardiac acute events allowing a non-surgical management of these individuals. PMID- 1512813 TI - A comparison of amrinone and glucagon therapy for cardiovascular depression associated with propranolol toxicity in a canine model. AB - This study's objective is to evaluate the ability of glucagon and amrinone to reverse propranolol induced cardiovascular depression in a canine model, compared to a control of normal saline. The study design included 18 animals which received intravenous propranolol (10 mg/kg) resulting in significant depression in heart rate, cardiac output, mean arterial pressure, maximal ventricular dP/dt and stroke volume. Each canine was randomly assigned to one of three treatment groups; controls (normal saline only), glucagon (20 micrograms/kg bolus) and amrinone (4 mg/kg bolus). Cardiovascular parameters were monitored at 1, 6, 11, 21 and 31 min after treatment was rendered. Multiple comparison procedures at each time period controlled the overall alpha-level at .05. Compared to control animals, both amrinone and glucagon were effective in reversing propranolol induced depression of dP/dtmax at 6 and 11 min for glucagon and 11 min for amrinone and cardiac output at 1, 6 and 11 min for glucagon and 1 min for amrinone. Amrinone and glucagon significantly increased stroke volume over control values at 1 min and tended to do so at the remaining time periods. The two days caused a similar degree of arteriolar vasodilation which was significantly greater than that seen in control animals at 1 and 6 min. Beta blocker induced bradycardia did not respond significantly to amrinone while glucagon induced a tachycardia which is unique to canines. It is concluded that in this canine model, amrinone appears to be an effective therapeutic alternative to glucagon for reversing depressed dP/dtmax, cardiac output and stoke volume induced by propranolol toxicity. Unlike glucagon, amrinone appears to lack positive chronotropic activity which may limit its clinical utility in the treatment of beta blocker overdose. PMID- 1512814 TI - Rapid onset of seizures following aspiration of viscous lidocaine. AB - A 2 year-old drank from a bottle of viscous lidocaine. Coughing and choking were prompt, and seizures began within 10 to 15 seconds. Intraosseous phenobarbital 40 mg/kg stopped seizures temporarily, 30 mg/kg more plus lorazepam 20 mg/kg were needed for complete control. Suctioning of the airway revealed viscous material compatible with the drug. Bilateral hilar pneumonia ensued rapidly. The syndrome of inappropriate antidiuretic hormone secretion occurred and was countered appropriately. Intubation, performed on admission, could not be discontinued. The adult respiratory distress syndrome, characterized by a typical diffuse X-ray pattern and poor oxygenation, developed. Bilateral pneumothoraces complicated care. The patient required 14 days of extracorporeal membrane oxygenation before recovery. A lidocaine level was obtained at 4 h post-ingestion and was 0.5 micrograms/mL (2 mumol/L). The rapid onset of seizures suggests that the drug was absorbed from the pulmonary bed. This possibility is supported by the finding of viscous-lidocaine-like material in the trachea, the rapid development of aspiration pneumonia, and the development of adult respiratory distress syndrome, which has been observed in adults when lidocaine was used in the trachea for procedures. PMID- 1512815 TI - Mercury clearance from human plasma during in vitro dialysis: screening systems for chelating agents. AB - Two in vitro systems were evaluated as potential screening methods for determining the most effective chelating agents for use in patients with inorganic mercury poisoning undergoing hemodialysis. The first system consisted of an in vitro clinical hemodialysis unit and the second system consisted of an in vitro equilibrium dialysis procedure. Both systems utilized pooled human plasma. Ten chelating agents were evaluated in these systems to determine their ability to enhance mercury clearance from human plasma. In the absence of chelators, plasma clearance of mercury was negligible. Of the chelating agents tested, 2,3-dimercaptopropanolol, which enhances biliary and fecal excretion of mercury poisoning, and dithiothreitol did not enhance mercury clearance at 90 min in the hemodialysis system. N-acetylcysteine appeared to be the most effective chelating agent of those tested in the hemodialysis system. N-acetylcysteine produced a 73% decrease in perfusate mercury concentration at 90 min. The results of equilibrium dialysis mirrored those of the hemodialysis in that N acetylcysteine significantly enhanced mercury transfer across the dialysis membrane into the dialysate whereas dithiothreitol did not. If in vivo experiments confirm the present findings, then in vitro dialysis from pooled human plasma either using a standard clinical hemodialyzer or equilibrium dialysis system will be useful screening tools. Our results suggest that equilibrium dialysis may be a convenient and cost effective method to screen potential chelating agents as complementary to hemodialysis for the treatment of inorganic mercury poisoning. PMID- 1512816 TI - Rhabdomyolysis and acute renal failure following carbon monoxide poisoning: two case reports with muscle histopathology and enzyme activities. AB - Two patients with carbon monoxide poisoning are presented, both of whom suffered rhabdomyolysis complicated by acute renal failure. One patient, an attempted suicide, developed a compartment syndrome of the right thigh that required fasciotomy and recovered after a period of hemofiltration and hemodialysis. Muscle biopsy appearances were consistent with partial muscle infarction. The other patient, rescued from a smoke filled room, exhibited raised creatine kinase but no evidence of muscle swelling. He developed anuric renal failure and adult respiratory distress syndrome and died despite maximum intensive care. Muscle biopsy showed early evidence of muscle necrosis. In both cases there was a marked reduction of enzyme activities in the muscle biopsy consistent with metabolic derangement. Although there was a clinical compartment syndrome in the first case, there was no muscle swelling at the time of biopsy or subsequently in the second case. A direct toxic effect of carbon monoxide may thus have been an important mechanism contributing to the muscle necrosis in the second case, although local ischemia may have been an exacerbating factor in the first case. PMID- 1512817 TI - A case of barbiturate poisoning with a readily-accessible laboratory reagent. AB - We report a patient with barbiturate intoxication due to surreptitious ingestion of barbital buffer from a clinical laboratory. Although detected in the urine toxicology screening test using an immunologic technique, this agent was not recognized in the more specific serum analysis done by gas-liquid chromatography. Barbital buffer is an effective long-acting sedative-hypnotic and is widely available from the laboratory shelf. It may not be reported by very specific analytical methods. PMID- 1512818 TI - Use of the scan statistic to detect temporal clustering of poisonings. AB - The purpose of this study is to explore the use of the scan test to detect temporal clustering of poison control center data. We applied the scan test to a computerized data set consisting of all cases of carbon monoxide poisoning reported to our Poison Control Center in 1988. Using a time window of three days, the scan test identified three statistically significant temporal clusters. A review of case and climatologic data revealed that two of the clusters were due to family outbreaks and one was due to a sudden cold spell. We conclude that the scan test is a potentially useful surveillance tool which can be easily applied to poison control center data. PMID- 1512819 TI - Periodicity of presentations of drugs of abuse and overdose in an emergency department. AB - In order to determine whether temporal factors impact on drugs of abuse and overdose presentations to an urban emergency department, we studied the records of 630 consecutive drug overdose presentations over a period from October 1987 to March 1990. Particular note was made of the time of day of presentation along with the nature of the drug(s) ingested. A significant curve (p less than 0.0005) was obtained for a 24 h period with a peak time of presentation being 6:32 pm (95% confidence interval of 1 h 54 min). Significant periodic rhythms were noted for cocaine, opiates, alcohol, analgesics, marijuana, and benzodiazepines. A 4.8 h periodic rhythm was demonstrated for cocaine, marijuana and alcohol-in combination. We conclude that the emergency department should be most prepared to treat the drug overdose patient in the early evening and emergency department staffing should reflect this peak in demand. PMID- 1512820 TI - Serum sodium and carbamazepine overdose. PMID- 1512821 TI - Carbamazepine overdose. PMID- 1512822 TI - Uric acid nephrolithiasis: pathogenesis and treatment. PMID- 1512823 TI - Has the American Urological Association made a difference? PMID- 1512824 TI - Endopyelotomy: comparison of ureteroscopic retrograde and antegrade percutaneous techniques. AB - To date 2 approaches have been developed for performing endopyelotomy, that is the antegrade and retrograde approaches. Experience with antegrade transnephrostomy endopyelotomy is quite large and the results have been excellent. However, the need for percutaneous nephrostomy and prolonged hospitalization have been 2 drawbacks to this approach. In contrast, experience with retrograde transureteral endopyelotomy is scant. However, a ureteroscopic approach is attractive from the standpoint of eliminating the need for a large nephrostomy tube and because of the possibility of performing this procedure on an outpatient basis or during a short hospital stay. We report our experience with antegrade and retrograde endopyelotomy in 41 patients. The hospital stay (3.4 versus 4.0 days), nephrostomy tube size (8F to 10F versus 20F to 22F) and nephrostomy tube duration (2.9 versus 3.8 days) were all less with the retrograde approach. The initial success rate was similar between the 2 methods: 79% (retrograde) versus 78% (antegrade). However, the analgesic requirements (5.3 versus 3.5 doses) and the occurrence of significant complications (that is late ureteral stricture in 20%) were greater with the ureteroscopic approach. With the methods currently available, we believe that antegrade endopyelotomy is the preferred approach for endopyelotomy. PMID- 1512825 TI - Treatment of osseous metastases secondary to renal cell carcinoma. AB - Osseous metastases occur in 25 to 50% of the patients with metastatic renal cell carcinoma. We retrospectively reviewed our experience with 14 patients who underwent 20 palliative orthopedic procedures for treatment of bony metastases secondary to renal cell carcinoma. Of the patients 6 presented after nephrectomy (group 1) and 8 presented initially with osseous metastases (group 2). Only 1 of the group 2 patients underwent adjunctive nephrectomy. Overall, 5 of 14 patients (36%) presented with fracture and 9 of 14 (64%) presented with impending fracture. Five patients required multiple procedures. A total of 7 lesions had been previously treated with external radiation. Of the 20 orthopedic procedures 17 (85%) resulted in significant functional improvement and 18 (90%) resulted in significant relief of pain. There were 4 major complications in the series, including 2 culminating in amputation. Average survival after palliative orthopedic procedures was 22 months (range 7 to 64 months) with a 1-year survival rate of 58%. Orthopedic palliation of osseous metastases from renal cell carcinoma is effective, and our experience indicates that the majority of renal cancer patients with bone metastases will survive long enough to benefit from palliative orthopedic procedures. PMID- 1512826 TI - A community study of bladder cancer screening by the detection of occult urinary bleeding. AB - A possible method of improving the prognosis of bladder cancer may be the widespread introduction of screening. We investigated the ability of urine dipsticks to detect early bladder cancer in a group of men in the community. In 2,356 men more than 60 years old the urine was tested with a dipstick for the presence of blood. The subjects then tested their own urine on 10 subsequent occasions. Of the men 474 (20%) had dipstick hematuria and 319 agreed to undergo urological investigation. An asymptomatic bladder tumor was found in 17 men, associated in 10 with abnormal urine cytological findings. Urine dipsticks for the detection of red cells provided an inexpensive, simple and acceptable screening test for bladder cancer. However, introduction of generalized population screening by this method would produce large numbers requiring investigation. Combining urine cytology with dipstick hematuria results may provide a realistic alternative and further evaluation of the effectiveness of screening for bladder cancer in the community is required. PMID- 1512827 TI - Interleukin-6 activity in urine and serum in patients with bladder carcinoma. AB - To investigate the correlation between interleukin-6 and urothelial neoplasms, interleukin-6 activities in blood and urine samples of patients with bladder carcinoma were measured with a proliferation assay using an interleukin-6 dependent murine hybridoma clone, MH60.BSF2. A total of 43 patients and 15 normal volunteers were entered into this study. All of the patients were examined preoperatively and 26 were reexamined more than 6 days postoperatively to eliminate the effect of surgical injury on interleukin-6 secretion. The interleukin-6 titers in urine and serum increased in accordance with the progression of the tumor stage, and tumor removal induced a remarkable decrease in the titer of urinary interleukin-6. Although the interleukin-6-producing site has not been elucidated yet, our study suggests that interleukin-6 activity in bladder carcinoma patients may reflect the immunoreaction against the tumor in local urothelium. PMID- 1512828 TI - Intravesical lidocaine: topical anesthesia for bladder mucosal biopsies. AB - The intravesical instillation of lidocaine solution has been used as a topical form of anesthesia for bladder biopsies. We performed 63 ambulatory procedures in which multiple cold-cup biopsies were obtained during cystoscopy. There was no need for electrocautery. All patients tolerated the procedure well and were discharged from the office immediately thereafter. There were no changes in heart rate or blood pressure during the procedures. Serum concentrations of lidocaine were measured in 10 patients at 5, 10 and 30 minutes, and they were clinically insignificant. This simple office procedure can be used for the diagnosis and followup of patients with carcinoma in situ of the bladder. PMID- 1512829 TI - Management of stage T1 superficial bladder cancer with intravesical bacillus Calmette-Guerin therapy. AB - We reviewed our results with 86 patients who had a pretreatment history of a stage T1 tumor. All patients were treated with transurethral resection of all visible tumor followed by intravesical bacillus Calmette-Guerin (BCG) and many patients received additional maintenance therapy. Local recurrences were treated with repeat transurethral resection followed by additional BCG. Median followup was 59 months, with a range of 9 to 149 months. Overall, 78 of 86 patients (91%) were free of tumor recurrence with BCG therapy. This result includes 69% of the patients who responded to the initial transurethral resection and intravesical BCG, and 22% who ceased having tumors after additional treatments for local recurrences. Only 7% of the patients had progression to stage T2 tumors after BCG therapy. Grade of the stage T1 tumor, concurrent carcinoma in situ and tumor multiplicity before BCG did not predict tumor recurrence or progression. Of patients with recurrences after BCG therapy, those with stage T1 tumors had a higher rate of progression compared to those with stage Ta tumors but the difference was not statistically significant (p = 0.086). These data clearly support the efficacy of transurethral resection plus intravesical BCG immunotherapy in the treatment of stage T1 tumors as well as in the prevention of disease progression. PMID- 1512830 TI - Distribution of 486P 3/12 antigen, ABO(H) blood group antigen and T antigen in cystectomy specimens from patients with stage T2 transitional cell carcinoma of the bladder. AB - We used monoclonal antibody 486P 3/12, anti-ABO(H) antibodies and anti-T antigen lectins to detect malignant transformation in cystectomy specimens from patients with stage T2 transitional cell carcinoma of the bladder. We used an immunoperoxidase technique to do extensive chessboard-like mapping studies in 6 cystectomy bladders with stage T2 lesions and 1 normal bladder from a multiorgan donor as control to characterize antigen expression. Increased 486P 3/12 antigen expression, decreased ABO(H) expression and T antigen deletion were detectable not only in the tumor area but also in tumor-surrounding areas classified as benign. We believe that cells with abnormal antigen expression are a source of tumor recurrence and can be identified with our method of quantitative immunocytology. PMID- 1512831 TI - Late decompensation of neobladder. AB - We report on 6 patients in whom we constructed detubularized ileocolonic neobladders in conjunction with cystectomy to treat invasive transitional cell carcinoma of the bladder. The patients had delayed complete or partial decompensation of the neobladder after an initial interval of normal voiding. Two patients experienced complete decompensation with inability to empty in the absence of urodynamic, cystoscopic or radiographic evidence of outlet obstruction. The other 4 patients had greater than 400 cc residual urine without evidence of outlet obstruction. The mean interval to decompensation after the initial period of normal voiding was 12.8 months (range 4 to 21). All 6 patients had a reservoir capacity of greater than 800 cc. We also constructed neobladders in 3 other patients for similar indications. These 3 patients have a neobladder capacity of less than 800 cc and all are voiding to completion with followup of 19 to 32 months. We hypothesize that neobladder decompensation is due either to creation of an excessively large pouch alone or in combination with a poor Valsalva ability. Until we know the neobladder capacity required for continence that will simultaneously allow for complete emptying, all patients should be advised of the possible need for intermittent self-catheterization. Urological followup should include monitoring of post-void residual urine volume to detect failure to empty early before irreversible decompensation occurs. PMID- 1512832 TI - Reproducibility in monitoring nocturnal penile tumescence and rigidity. AB - The evaluation of sexual dysfunction has improved with the advent of methods to test nocturnal penile tumescence that also monitor penile rigidity. Earlier techniques may not have recorded abnormal rigidity despite normal tumescence. To test the reproducibility of penile tumescence and rigidity, the results of initial and repeat tracings performed a mean of 39 days apart were compared in 17 patients (median age 62 years). Three nocturnal patterns were identified. 1) Among the 17 patients the initial penile tumescence and rigidity pattern was reproduced on repeat testing in 15. 2) Patterns that were not reproduced in the other 2 patients were explained by the ingestion of alcohol or because of a febrile illness during the period monitored. 3) Nocturnal penile rigidity and tumescence tracings from these patients reproduced previous patterns. Monitoring of nocturnal penile tumescence and rigidity is a useful and reproducible tool in the evaluation of male sexual dysfunction. PMID- 1512833 TI - Preliminary report: penile vein occlusion therapy: selection criteria and methods used for the transcatheter treatment of impotence caused by venous-sinusoidal incompetence. AB - Penile vein occlusion therapy is a fluoroscopic guided technique developed for treating venous-sinusoidal incompetence in patients with erectile dysfunction. We report our experience with 22 patients who have been followed for greater than 1 year. Catheterization of the veins draining the penis was technically possible in 20 of 22 patients (91%). Of these 20 patients 5 (25%) were cured and 9 (45%) had significantly improved erectile function. All 5 patients (100%) with venous sinusoidal incompetence plus normal cavernous arterial flow, no glans or corpus spongiosal shunts, and bilateral complete coil occlusion of the crural and common crural veins were cured. No deterioration of function was noted at 1 and 2 years. Patient selection and bilateral occlusion of the penile veins are essential to achieve successful penile vein occlusion therapy. PMID- 1512834 TI - A screening study of prostate cancer in high risk families. AB - In a study of the familial risk of prostate cancer 17 sets of 2 brothers with prostate cancer were identified. A total of 34 first-degree relatives of these probands (sons and brothers, 55 to 80 years old) underwent an intensive screening examination that included prostate specific antigen, digital rectal examination, transrectal ultrasound and systematic as well as clinically directed core needle biopsies. Previously unsuspected and clinically relevant cancers were found in 8 men (24%), compared to the approximately 1 expected (p less than 0.01). Of these cancers 2 were detected by the systematic biopsies. This study emphasizes the importance of thorough screening in first-degree relatives of prostate cancer patients. PMID- 1512835 TI - Deoxyribonucleic acid cytometry and histological findings before and after 125iodine implantation of primary prostate cancer. AB - Deoxyribonucleic acid (DNA) flow cytometry and light microscopy were performed in pre-radiotherapy and post-radiotherapy biopsies obtained from the primary tumor in 31 patients with prostate cancer. Radiotherapy was applied by means of transperineal 125iodine (125I) implantation. Of the patients 21 had pretreatment biopsies and in 19 of these biopsies also were performed 1 and/or 1 1/2 years after the 125I implantation. Posttreatment biopsies were available for DNA flow cytometry in 12 additional patients without pretreatment DNA flow cytometry assessment. Of the 21 pretreatment biopsies 7 were diploid, 6 tetraploid and 8 aneuploid. All 31 posttreatment biopsies were either tetraploid (21) or aneuploid (10). All 6 pretreatment diploid tumors became tetraploid after radiotherapy. At 1 and/or 1 1/2 years after 125I implantation residual tumors were found in 28 of 31 prostatic glands. The high frequency of nondiploid DNA stemlines 1 or more years after 125I implantation and the high rate of residual tumor leave some doubt about the radiocurability of prostate cancer by the chosen radiotherapy technique. PMID- 1512836 TI - Moni's window operation: a new surgical technique to create a sperm reservoir in congenital vasal agenesis. AB - A new surgical technique to create a sperm reservoir in bilateral congenital vasal agenesis is described. The technique is simple to perform and sperm recovery is easy. Of the 4 cases treated with this technique between 1989 and 1990 pregnancy has resulted in 1 (25%). In all 4 cases (100%) motile sperm could be aspirated from the spermatocele created. PMID- 1512837 TI - The Raz bladder neck suspension: results in 206 patients. AB - We reviewed the charts of 206 patients who underwent the Raz bladder neck suspension between January 1984 and June 1990 for stress urinary incontinence. Mean followup was 15 months. Overall, our results demonstrated a successful outcome (cure or rare stress urinary incontinence not requiring protection) in 186 of 206 patients (90.3%). Cox multivariant analysis showed that the only predictor of outcome was the degree of preoperative stress urinary incontinence (mild, moderate or severe, p less than 0.001). When the results were stratified by degree of incontinence preoperatively 20 of 21 patients (95%) with mild, 151 of 162 (93%) with moderate and 15 of 23 (65%) with severe incontinence had a successful outcome. No statistical correlation was found with patient age, number of prior operations, hysterectomy, urgency incontinence or menopause. For the patients who failed, the mean interval to recurrent stress urinary incontinence was 5 months. Significant urgency incontinence was present preoperatively in 58 of the 204 patients (29%), with postoperative resolution in 66%. De novo urgency incontinence occurred in 7.5%. Complications included secondary prolapse (6% of the patients), prolonged retention (2.5%) and suprapubic pain (3%). In summary, the Raz bladder neck suspension for correction of stress urinary incontinence has been successful in more than 90% of this patient population. PMID- 1512838 TI - The Cantwell-Ransley technique for repair of epispadias. AB - A total of 26 boys with bladder exstrophy (20) and epispadias (6) underwent initial urethral reconstruction between 1988 and 1991 using the Cantwell-Ransley technique. Penile reconstruction included wide mobilization of the urethral plate from the underlying corpora based on a mesentery from the ventral penoscrotal skin, corporeal lengthening by dividing the suspensory ligaments and attachments to the undersurface of the pubis, urethral and glandular tubularization, chordee correction by medial incision of the corpora with anastomosis dorsal to the urethra and penile skin coverage. All exstrophy patients had adequate phallic length, with 13 having an intact urethral plate and 13 having had prior paraexstrophy skin flap interposition. Postoperatively, repairs were intubated with silicone stents for 10 days. Two urethrocutaneous fistulas developed, 1 of which closed spontaneously. One patient had a small degree of penile skin loss that did not affect the neourethra. All patients currently have a cosmetically acceptable penis and all but 1 (previously diverted) are voiding per urethram. The neourethra in such patients allows for easier access for endoscopy and the ventral position aids in maintaining correction of the dorsal chordee. The low complication rate of this procedure coupled with the better anatomical configuration of the neourethra makes it useful for urethral and penile reconstruction in the exstrophy and epispadias patient. PMID- 1512839 TI - Circumcision in hemophilia: the use of fibrin glue for local hemostasis. AB - Circumcision can be fatal in hemophilia patients unless they are treated with the missing coagulation factor. We describe 10 severe hemophilia patients in whom circumcision was performed with local fibrin glue instead of infusion of factor concentrate. Of the 10 patients 3 had postoperative bleeding and only 2 of them required infusion of factor VIII concentrate. Fibrin glue is a useful treatment modality for circumcision in patients with bleeding diathesis, and it is safer and cheaper than the infusion of factor concentrate. PMID- 1512840 TI - Giant ureteral stone. AB - A 58-year-old man presented with left flank pain and a high grade fever. Investigations revealed left pyonephrosis with a left renal stone and a giant left ureteral stone. Nephroureterectomy was performed. The ureteral stone measured 13 cm. long and weighed 90 gm. PMID- 1512841 TI - Ureteroarterial fistula: a case report. AB - Ureteroarterial fistulas are rare, with less than 20 well documented cases reported. We report a case of a fistula between the left external iliac artery and the left ureter in a patient who underwent a previous operation for bladder cancer. The diagnostic and therapeutic approaches in these rare but high risk patients are discussed. PMID- 1512842 TI - Levator hernia. AB - We report a case of a hernia through the pelvic floor presenting as a paravaginal mass following a transvaginal fascial sling procedure. At exploration herniation through a defect in the pelvic floor was identified and repaired. To our knowledge this is the first reported case of levator hernia. The clinical and radiological findings and anatomy are presented, and treatment recommendations and etiology are discussed. PMID- 1512843 TI - Concomitant carcinoma of the penis and urethra treated with a unique method of continent diversion. PMID- 1512844 TI - Clozapine-induced priapism. AB - Priapism may be a side effect of certain medications. We present a case of priapism associated with the nonphenothiazine antipsychotic drug clozapine. The possible mechanism for the drug-induced priapism is discussed. PMID- 1512845 TI - A new therapeutic concept for long-lasting iatrogenic priapism: a case report. AB - In a therapeutic attempt on an 18-year-old patient with iatrogenic priapism lasting for more than 2 weeks after internal urethrotomy, intracavernous lysis was commenced with 80,000 IU streptokinase per hour. Following a dosage of 300,000 IU streptokinase the lysis was stopped because of severe bleeding from the urethrotomy scar. At 4 weeks after the patient was discharged from the hospital he reported normal erections and intercourse, while single potential analysis of cavernous electrical activity and ultrasound returned to normal. Provided there are no contraindications, intracavernous lysis seems to be an effective treatment for long-lasting priapism induced by intracavernous thrombosis. PMID- 1512846 TI - Primary carcinoid tumor of the testicle: a case report and management schema. AB - A case of primary testicular carcinoid is presented in which extensive testing for peptide hormones was done. None was found suggesting that such tumors may be nonfunctional. A systematic approach to the evaluation and treatment of testicular carcinoid is presented. PMID- 1512847 TI - Sertoli-Leydig cell testicular tumor: case report and review of sex cord/gonadal stromal tumor histogenesis. AB - We describe a case of well differentiated Sertoli-Leydig cell tumor in a testicle. Previously, this tumor has only been illustrated histologically. The existence of a male homologue to the female arrhenoblastoma containing Sertoli and Leydig cells again supports the current hypothesis of gonadal development, and the common steps found in the male and female pathways. PMID- 1512848 TI - Crossed ectopia of left vas deferens, leaving ipsilateral seminal vesicle in normal position. AB - A 19-year-old man with crossed ectopia of the vas deferens was investigated with special reference to right hydronephrosis and renal dysfunction. There was no vesicoureteral reflux. The left kidney was hypoplastic or dysplastic and the left ureter emptied into the left seminal vesicle. The right malrotated hydronephrotic kidney was in the lumbar position. The right lower ureter communicated with either the right seminal vesicle or the ampullary portion of the left vas deferens and drained into the bladder at the normal site. The end of the right vas deferens was dilated. The left vas deferens crossed the midline and opened into the right seminal vesicle, leaving the ipsilateral seminal vesicle in the normal position. A search of the literature failed to reveal any similar anomalies. PMID- 1512849 TI - Cryptococcal prostatic abscess associated with the acquired immunodeficiency syndrome. AB - A case of cryptococcal prostatic abscess in a 28-year old man with the acquired immunodeficiency syndrome is presented. This is a unique presentation of a cryptococcal prostatic infection and of a prostatic abscess. The diagnosis and management are discussed, and the literature is reviewed. PMID- 1512850 TI - The history of research training and career awards in urological science supported in the National Institute of Diabetes and Digestive and Kidney Diseases. AB - Urology research and training grants were placed into a separate research program in 1979. Research emphasis and the context of training programs have changed from a focus on urolithiasis in the 1970s to a broader range of urological disorders in the 1980s. From 1977 to 1990, 49 applications were submitted by 47 applicants for research training/career development support and 39% of the applications were successful. From 1977 to 1987 medical doctors applying for research/career training had a 75% success rate in subsequent National Institutes of Health research grant applications, and basic scientists had a 67% success rate. Of the 33 former trainees supported on institutional training grants during the last 14 years 76% were medical doctors and 24% were basic scientists. From 1977 to 1987, no former medical doctors or basic scientists from institutional training grants have a record of applying to the National Institutes of Health for research grant support. The urology community needs to capitalize on the available opportunities to expand the training programs to increase the number of physician and urological research scientists. PMID- 1512851 TI - Re: The incidence of multicentricity in renal cell carcinoma. PMID- 1512852 TI - Re: Computerized analysis of smooth muscle fibers in potent and impotent patients. PMID- 1512854 TI - Re: Subepididymal orchiectomy: the acceptable alternative. PMID- 1512853 TI - Re: Computerized analysis of smooth muscle fibers in potent and impotent patients. PMID- 1512855 TI - Re: The penile plication procedure: an alternative method for straightening penile deviation. PMID- 1512856 TI - Significance of asymptomatic bacteriuria in spinal cord injury patients on condom catheter. PMID- 1512857 TI - Bacillus Calmette-Guerin abrogates in vitro invasion and motility of human bladder tumor cells via fibronectin interaction. AB - Intravesical bacillus Calmette-Guerin (BCG) has been shown to be an effective treatment for superficial transitional cell carcinoma of the bladder (TCC). The mechanisms by which BCG limits tumor cell activity have thus far been unclear. We investigated the interaction between BCG and invasive human TCC cell line EJ in an in vitro invasion assay. We observed that BCG inhibited the invasion of EJ cells through an artificial basement membrane. In terms of the steps involved in tumor cell invasion, i.e. attachment, proteolysis, and motility, BCG was found to limit tumor cell motility. Attachment and proliferation of tumor cells were not affected by BCG. The effects of BCG on tumor cell migration were mediated by fibronectin (FN), a basement membrane glycoprotein component. Abrogation of BCG FN-tumor cell interactions with anti-FN antibodies eliminated the ability of BCG to block tumor cell invasion. Fibronectin appears to link BCG and tumor cells via independent FN binding receptors to separate domains of the FN molecule. The molecular mechanism by which BCG may limit tumor cell motility may be its ability to protect against the formation of specific FN sequences as a result of protease cathepsin B digestion. A 31 kD and 27 kD FN band were absent from purified or tumor cell associated cathepsin B digestion when incubated in the presence of BCG, but present in the absence of BCG. Furthermore when purified from SDS polyacrylamide gel electrophoresis, the fragments were shown to have motility stimulating activity for the invasive EJ cells. These findings suggest that BCG functions as a potent inhibitor of tumor cell invasion. We conclude that BCG fibronectin-tumor cell interactions may have a direct influence on the invasive mechanisms, such as motility, of tumor cells. PMID- 1512858 TI - Suramin inhibits growth factor binding and proliferation by urothelial carcinoma cell cultures. AB - Suramin is a polyanionic compound recently noted to inhibit growth factor action and proliferation of several types of neoplastic cells in vitro. Data from clinical trials show antineoplastic activity against some prostatic and adrenal cortical carcinomas. Suramin is excreted unmetabolized into the urine suggesting possible application in treatment of urothelial carcinoma and prompting us to examine the drug's effect on growth factor binding and cell proliferation by two urothelial carcinoma cell lines. Half-maximal inhibition of 125I-epidermal growth factor (EGF) binding to T24 and HT1376 cells was produced by suramin concentration of approximately 300 and 100 microM, respectively. The corresponding value for 125I-insulin-like growth factor 1 (IGF1) binding was 60 microM for both cell lines. Inhibition of T24 and HT1376 growth was virtually complete at suramin concentrations in the range achievable clinically. PMID- 1512859 TI - The influence of ovariectomy and estradiol replacement on urinary bladder function in rats. AB - Female Fischer 344 rats were ovariectomized or sham operated and treated with oil or estradiol cypionate (100 mg./100 gm./month) for two or four months. Rats were then placed in metabolism cages for measurement of micturition characteristics, and bladders were removed for bladder strip studies. Ovariectomy had no effects on micturition characteristics. However, estradiol treatment of ovariectomized rats caused significant increases in water consumption and urine excretion, and in mean and maximal micturition volumes compared to both ovariectomized and sham operated rats. These effects were more pronounced at four months. Estradiol treatment also caused significant increases in bladder body mass, while ovariectomy was without effect. Two months after ovariectomy and/or estradiol treatment, there were no differences in contractile responses of bladder body or base strips to contractile agents when compared to shams. However, after four months, ovariectomy caused significant decreases in contractile responsiveness to nerve stimulation. ATP, carbachol, and KCl compared to sham-operated rats. Estradiol treatment caused increased responsiveness to nerve stimulation, ATP, carbachol, and KCl compared to ovariectomized rats, and to carbachol compared to sham operated rats. Possible causes for the effects of ovariectomy on bladder contractility include decreases in calcium influx. Although estradiol reversed the effects of ovariectomy on bladder function, in addition we observed some indirect effects which were probably the result of estradiol-induced polyuria and increases in bladder mass. PMID- 1512860 TI - Intravesical electrical stimulation--an experimental analysis of the mechanism of action. AB - The working mechanism of intravesical electrical stimulation (IVES) was evaluated in alpha-chloralose anaesthetized cats and rats. IVES involved a direct activation of bladder mechanoreceptor afferents of the A delta type and as a consequence a central reflex activation of the detrusor. The detrusor response was abolished by bilateral transection of the S1-S3 dorsal roots and by intravesical instillation of lidocaine. The optimal stimulation frequency was 20 Hz. The results offer a theoretical rationale for the use of IVES as treatment of weak detrusor contractility in man. PMID- 1512861 TI - Response of bladder, urethral and intracavernous pressure to ventral lumbosacral root stimulation in Sprague-Dawley and Wistar rats. AB - Six Sprague-Dawley and six Wistar rats were used for electrostimulation of the L5 to S2 ventral roots. Landmarks for identification of the roots were developed; bladder, urethral and intracavernous pressures were recorded; and tail and leg movements were checked. Urethral sphincter contraction was elicited by stimulation of the L5-L6 ventral roots, while bladder contraction and penile erection were mediated by the L6-S1 ventral roots. The best sphincteric response and intracavernous pressure rise were obtained by stimulation of the L6 ventral root, and the highest bladder pressures by stimulation of the S1 ventral root. Stimulation of the S1-S2 ventral roots provoked ipsilateral tail movement; of L6, tail movement, hindleg muscle twitch, and slight toe spread; and of L5, hindleg stretch and plantar flexion. No significant differences were found between the two strains of rats, although a higher bladder pressure was recorded during stimulation of the L6 ventral root in Sprague-Dawley rats, which might be explained by a small caudal shift of the sacral parasympathetic nucleus in the Wistar strain. PMID- 1512862 TI - Urinary bladder function in rats with hereditary diabetes insipidus; a cystometrical and in vitro evaluation. AB - Bladder function was investigated in female rats with hereditary diabetes insipidus (DI) and in healthy controls, in vivo by means of recordings of micturition pattern and cystometry, and in vitro in organ bath experiments. Rats with DI exhibited bladder hypertrophy, the weight of the bladder in these rats being two times that of controls. Recordings of micturition pattern showed that DI-rats had an increased 24 hour diuresis and micturition volume, and decreased micturition interval in comparison with controls. Cystometry recordings revealed increased bladder capacity and micturition volume in DI-rats. However, in these rats basal bladder pressure and threshold pressure were lower than in controls. No significant changes in micturition pressure or bladder compliance were observed, and none of the rats had residual urine. In organ bath studies, a lower maximal response to electrical field stimulation was obtained in bladder strips from DI-rats, than in the control strips, when expressed relative to the response elicited by K(+)-solution. When activated by field stimulation, the DI-bladder strips and the control strips had similar sensitivity to muscarinic receptor blockade with scopolamine at all stimulation frequencies. The sensitivity to carbachol was similar in the two groups. The results suggest that the increased functional demands of DI on the detrusor do not result in major changes pre- or postjunctionally. Further, several of the previously reported urinary bladder changes observed in rats with diabetes mellitus (DM) are similar to those now reported in rats with DI, emphasizing the importance of an increased diuresis per se for the development of alterations in bladder function. However, in contrast to the findings in DM rats, the sensitivity to electrical stimulation of nerves during blockade of muscarinic receptors was similar in DI-rats and their controls. This supports our previous suggestion that the increased resistance to muscarinic receptor blockade of the bladder in DM-rats at low stimulation frequencies is induced by the disease (diabetes mellitus) as such and not by the increased diuresis. PMID- 1512863 TI - Studies on experimental bladder outlet obstruction in the cat: long-term functional effects. AB - Experimental bladder outlet obstruction in cats induces a significant increase in the in vivo leakage pressure. The effects of obstruction on the detrusor function were analyzed, using control, 3, 6 and 12 month obstructed cats. The in vivo leakage pressures were substantially increased in all obstructed groups. From a previous study on the short-term effects of obstruction in the cat; although there was an immediate increase in pressure, there were no significant differences between control bladders and two week obstructed bladders in: bladder weight, peak pressure response to field stimulation and bethanechol, and emptying of the in vitro whole bladder model. In this current study, although there was no direct relationship between duration of obstruction and severity of the impaired pharmacological response of the isolated whole bladder, there was a direct relationship between the magnitude of the increase in bladder weight, leakage pressure, and impaired functional response of the in vitro whole bladder. In this regard the cats were separated into four groups: controls and shams (average bladder weight 2.95 gm.), obstructed group 1 with bladder weights less than 6.0 gm. obstructed group 2 with bladder weights between 6 and 10 gm., and obstructed group 3 with bladder weights greater than 10 gm. The results can be summarized as follows: A) In vivo leakage pressures were significantly increased in all obstructed groups, and progressively higher in proportion to the bladder weights. B) Bladder capacity significantly increased in all, being greatest in obstructed group 3. C) The magnitude of the response to field stimulation of obstructed groups 1 and 2 were significantly greater than the response of control bladders at virtually all frequencies. The frequency response curve of obstructed group 3 was similar to control. D) The ability of the bladder to empty in response to field stimulation was significantly reduced in all obstructed groups. The magnitude of the decrease was proportional to the increase in bladder weight. E) There were no differences between control and obstructed bladders in the pressure response to bethanechol or KCl; the ability of both bethanechol and KCl to empty the bladder was reduced in the obstructed groups. In general, the presence of bladder enlargement was accompanied by significant alterations in the ability of the in vitro bladder to empty in response to field stimulation, bethanechol, and KCl.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1512864 TI - Correlation of contractile function and passive properties of rabbit urinary bladder subjected to outlet obstruction--an in vitro whole bladder study. AB - The present study investigated the correlation between contractile function and passive properties of rabbit urinary bladder subjected to outlet obstruction. Mild bladder outlet obstruction was induced by placing silicone rings (7 mm. diameter) around the bladder necks of male New Zealand rabbits. The animals were sacrificed after 2 weeks of obstruction. Contractile function was evaluated by measuring the response of the in vitro whole bladder to 500 microM bethanechol administration. Passive properties was assessed by performing in vitro cystometry and stress-relaxation techniques utilizing six different infusion rates. When the intravesical pressure reached 30 cm. H2O the infusion was stopped, allowing the bladder to relax and intravesical pressure to drop to a steady state level. The results can be summarized as follows: 1) Although the intravesical pressure response to bethanechol was about the same in control (13.3 cm. H2O) and obstructed (12.4 cm. H2O) bladder, the obstructed bladder emptied significantly less than control (20.4 vs 89.3%); 2) the results of the passive properties study showed that bladder stiffness was significantly higher at all infusion rates in the obstructed bladder, 3) the obstructed bladder showed significantly less relaxation after rapid stretching of the whole bladder by high speed fluid infusion; 4) histological examination of obstructed bladders revealed marked fibrous thickening of the serosal layer, interstitial fibrosis of the muscle layers, and hypertrophic and/or degenerative changes of the muscle fibers. In summary, 2 weeks after mild outlet obstruction of the urinary bladder the emptying ability, but not pressure generation, was reduced along with increased bladder stiffness and diminished capacity for stress-relaxation. Interstitial fibrosis and changing the properties of the smooth muscle cells might be involved in the functional impairment and deranged viscoelasticity of the urinary bladder after outlet obstruction. PMID- 1512865 TI - Electrical stimulation induced sphincter fatigue during voiding. AB - The stimulation of the sacral nerves to induce voiding is often associated with simultaneous contraction of the striated sphincter rendering micturition difficult or impossible. Rhizotomy of some sacral nerves was found to be necessary to facilitate voiding with stimulation. An main objective in the present experiment was to evaluate the feasibility of achieving the same result using electrical stimulation to fatigue the sphincter. In order to compare the effect of rhizotomy and fatiguing striated sphincter, the bladder outlet resistance was measured. S2 nerves were stimulated with 3 V, 35 Hz and 100 microseconds duration for 5 to 10 sec. Following S2 nerves stimulation the pudendal nerve was stimulated till we obtained sphincteric fatigue. The optimal parameter to induce sphincter fatigue were 3 V, 100-500 Hz and 100 microseconds. for 15-20 sec. The combined pressure-flow studies showed that fatiguing the sphincter via the pudendal nerve using these parameters was as good as cutting it in achieving bladder emptying with stimulation. PMID- 1512866 TI - Serologic survey for brucellosis in feral swine, wild ruminants, and black bear of California, 1977 to 1989. AB - A retrospective analysis of brucellosis serologic testing results in eight wildlife species in California from 1977 to 1989 was done. Samples were collected from 5,398 live-captured or hunter-killed animals and tested by combinations of up to six serologic tests for antibodies to Brucella spp. Twenty-three of 611 (3.8%) feral swine (Sus scrofa), one of 180 (0.6%) black bear (Ursus americanus), one of 355 (0.3%) California mule deer (Odocoileus hemionus californicus), and one of 1,613 (0.06%) blacktail deer (Odocoileus hemionus columbianus) samples were considered reactors. Suspect serologic reactions occurred in three of 619 (0.5%) desert bighorn sheep (Ovis canadensis nelsoni) and one of 355 (0.3%) California mule deer samples. Brucellosis is not considered an important wildlife health problem in California except in feral swine. PMID- 1512867 TI - Borrelia burgdorferi infection in white-footed mice (Peromyscus leucopus) in hemlock (Tsuga canadensis) habitat in western Pennsylvania. AB - White-footed mice (Peromyscus leucopus) were captured and their tissues sampled from 27 sites in seven counties of western Pennsylvania in 1990 for isolation and identification of Borrelia burgdorferi. Two hundred sixty mice were captured from which there were 27 isolations. Significantly more mice were captured and significantly more isolations made from hemlock (Tsuga canadensis) habitat than from deciduous species forest. Hemlock habitat is sparse and focal but evidently increases winter survival of mice, and thus possibly results in increased infection rates in mice. PMID- 1512868 TI - Epidemiology of raccoon rabies in Virginia, 1984 to 1989. AB - Geographical and temporal trends in reports of rabid raccoons (Procyon lotor) in Virginia were summarized for 1984 to 1989; 3,256 raccoons were submitted for rabies testing, of which 1,053 (32.3%) had rabies. Both the absolute number of rabid raccoons and the percent of rabid raccoons (number rabid divided by number submitted) were examined for seasonal and yearly trends. Geographically, the epidemic moved eastward and southward in the state. The seasonal trend showed bimodal peaks in late winter and early fall and a seasonal low in summer. The percent of rabies positive raccoons peaked 1 mo earlier than the absolute number of rabies positive raccoons. The peak in the number of rabies positive raccoons occurred in 1987, while the percent of rabies positive raccoons peaked in 1986. These trends were used to recommend timing and placement of oral vaccine as one strategy to control raccoon rabies in wildlife. PMID- 1512869 TI - Demonstration of rabies virus-specific antibody in the sera of free-ranging Iowa raccoons (Procyon lotor). AB - Between 1984 and 1988, a study was conducted to evaluate the frequency of rabies virus neutralizing antibodies in raccoons (Procyon lotor) in two counties in Iowa. Nine hundred eighty five raccoons were trapped and tagged in Guthrie and Cerro Gordo counties during the spring, summer and fall of each year. Sex, age and weight were recorded for each animal and a blood sample was collected. Serum samples were tested for the presence of serum neutralizing antibodies (SNA) by the rapid fluorescent focus inhibition test (RFFIT), mouse serum neutralization test (MSN), and an indirect fluorescent antibody (IFA) technique for detecting immunoglobulin G. Fifty-one raccoons (5%) were found to have SNA by the RFFIT. Thirty-six serum samples (24 with RFFIT antibody titer greater than 3.0, and 12 less than 3.0) were also tested by the MSN, with results correlating well with the RFFIT results (r = 0.86, P less than 0.01, Kappa = 0.93). In 35 raccoons with SNA by the RFFIT, six individuals had immunoglobulin G binding activity by the IFA test. These results provided serologic evidence of exposure of raccoons to rabies virus in an area free of enzootic raccoon rabies. PMID- 1512870 TI - Rodents are not a source of endogenously-produced, fecally-transmitted Caryospora bigenetica oocysts. AB - Fifteen Swiss-Webster mice (Mus musculus) and eight cotton rats (Sigmodon hispidus) were inoculated orally with Caryospora bigenetica oocysts. Feces from these animals were collected from 0 to 180 days postinoculation (DPI) and examined for endogenously-produced oocysts using Nomarski microscopy. Oocysts were recovered from mouse feces at 0, 1, 2, 3, 5, 7, 8, 10, and 14 DPI, and from cotton rat feces at 1, 2, and 9 DPI. The recovered oocysts were determined to be from the original inocula due to the presence of thick walls, polar granules, and Stieda and substieda bodies. All animals exhibited clinical signs at 8 DPI. Developmental stages of C. bigenetica were identified in various tissues of seven cotton rats found dead at 9, 10, 11, 12, and 13 DPI. Caryocysts were found in muzzle, tongue, footpad, scrotum, and rectum of mice and cotton rats at 30 DPI. Fecal samples collected from mice on 0, 8, 10, 12, 14, 16, and 18 DPI, and from cotton rats on 0, 9, 11, 13, 15, and 17 DPI were injected subcutaneously into 13 mice. Of the 13 mice, a Caryospora infection was observed only in the mouse inoculated with 0 DPI mouse feces. We propose that endogenously-produced C. bigenetica oocysts are not fecally-transmitted by Swiss-Webster mice or cotton rats. PMID- 1512871 TI - Cause-specific mortality of white-tailed deer as influenced by military training activities in southwestern Oklahoma. AB - Radio-telemetry was used to monitor movements and mortality of 56 white-tailed deer (Odocoileus virginianus) in response to intensive military training activities on West Range (18,000 ha), Fort Sill Military Reservation, Oklahoma. Cause-specific mortality was determined for 22 radio-collared deer, including adults (greater than or equal to 2.0-yr-old), yearlings (0.6-1.9-yr-old), and fawns (less than or equal to 75-day-old age group) from 1987 to 1989. Winter home ranges were largely confined to a 14,411 ha impact area centrally located on West Range. The mean annual mortality rate was 0.50 for adults and yearlings combined. Fifty percent of all adult and yearling mortality was attributed to military training activities, 28% to hunting, 16% to collisions with automobiles, and 6% to unknown causes. The mean monthly mortality rate was 0.61 for neonatal fawns and predation accounted for three of four mortalities. All captured deer in the greater than or equal to 2.6-yr-old, 82% in the 1.6-yr-old, 10% in the 0.6-yr old, and all deer in the less than 7-day-old age groups were seropositive for bluetongue virus (BTV). Our study strongly suggests that the consequences of military training activities should be considered in the management of white tailed deer herds on military installations. PMID- 1512872 TI - Blood profiles for a wild population of green turtles (Chelonia mydas) in the southern Bahamas: size-specific and sex-specific relationships. AB - Blood biochemical profiles and packed cell volumes were determined for 100 juvenile green turtles, Chelonia mydas, from a wild population in the southern Bahamas. There was a significant correlation of body size to 13 of the 26 blood parameters measured. Only plasma uric acid and cholesterol were significantly different between male and female turtles. The relationship between total plasma proteins and plasma refractive index was significant. The equation for converting refractive index (Y) to total plasma proteins (X) is Y = 1.34 + 0.00217(X). PMID- 1512873 TI - Serum chemistry values of the endangered San Joaquin kit fox (Vulpes macrotis mutica). AB - Serum chemistry values were obtained from 64 adult San Joaquin kit foxes (Vulpes macrotis mutica) in western Kern County, California (USA). The goal of the study was to establish normal chemistry values for this endangered species. No significant differences were found for mean values of alanine aminotransferase (217.1 IU/l), alkaline phosphatase (44.2 IU/l), cholesterol (145.6 mg/dl), total protein (5.8 g/dl), creatinine (0.63 mg/dl), calcium (8.2 mg/dl), albumin (3.0 g/dl), glucose (129.2 mg/dl), amylase (196.8 IU/l), sodium (153.7 mEq/l) and phosphorus (5.42 mg/dl) between sexes or seasons. Significant differences were noted for aspartate aminotransferase, blood urea nitrogen and potassium between seasons. Possible disturbances in normal hepatic and renal functions were noted. PMID- 1512874 TI - Ophthalmologic examination of the normal eye of the koala. AB - The ophthalmic examination of the koala (Phascolarctos cinereus) was undertaken to describe the normal in vivo structure. Twenty-two of 28 koalas examined were found to have normal eyes. Slit-lamp examination revealed unusual lamellae in the cornea, and mean keratometric readings were 59.3 +/- 3 diopters, corneal endothelial cell area of 381.4 microns2 +/- with a standard deviation of 46.8 microns2. No particular features were seen which would explain the susceptibility of this animal to ocular infection by Chlamydia psittaci. PMID- 1512875 TI - Pathological findings in the Hawaiian monk seal. AB - Postmortem examinations were performed on 45 Hawaiian monk seals (Monachus schauinslandi) collected during field research on the beaches of the Northwestern Hawaiian Islands (USA) from 1981 to 1985. Both males and females of all age groups, perinatal through adult, were examined. Frequent findings included parasites, trauma, cardiovascular disease (congenital and acquired), and respiratory infections. Emaciation was a common condition. All animals except neonates were infected with parasites; infection was severe in several cases. Splenic hematopoiesis was a universal histopathologic finding. Some cases exhibited lesions consistent with renal, gastrointestinal, and toxic disorders; ectopic tissue calcification; gallstones; and ophthalmologic and dental problems. PMID- 1512876 TI - Serologic survey for selected arboviruses and other potential pathogens in wildlife from Mexico. AB - During 1988 and 1989, a serologic survey of wildlife was conducted in northeastern Mexico to determine the presence, prevalence, and distribution of arboviruses and other selected disease agents. Eighty mammal specimens were tested. Antibodies to vesicular stomatitis-Indiana, Venezuelan equine encephalitis-Mena II, Rio Grande virus, and vesicular stomatitis-New Jersey were detected predominantly in small mammals. Deer and mouflon (Ovis musimon) had antibodies to bluetongue and epizootic hemorrhagic disease. Two species had serologic evidence of recent exposure to Francisella tularensis. A white-tailed deer (Odocoileus virginianus) had antibodies to Anaplasma marginale. All specimens tested for antibodies against Yersinia pestis and Brucella abortus were negative. Sera from 315 birds were tested for antibody against five equine encephalitis viruses and six avian pathogens. During 1988, antibodies to Venezuelan equine encephalitis-Mena II, Venezuelan equine encephalitis-TC83, St. Louis encephalitis, eastern equine encephalitis, and western equine encephalitis were detected in birds of several species. Antibodies to Pasteurella multocida and Newcastle disease virus were also detected. Birds from five species presented antibodies to Mycoplasma meleagridis. Specimens tested for M. gallisepticum, M. synoviae, and Chlamydia psittaci were negative. To the best of our knowledge, this survey represents the first serologic evidence of bluetongue, Cache Valley virus, epizootic hemorrhagic disease, Jamestown Canyon virus, vesicular stomatitis-Indiana, vesicular stomatitis-New Jersey, Rio Grande virus, and tularemia reported among wildlife in Mexico. PMID- 1512877 TI - Antibody response to canine distemper vaccine in African wild dogs. AB - Antibody levels against canine distemper virus were measured by means of an immunofluorescent antibody test prior to, and after, administration of a modified live virus booster vaccine to seven African wild dogs (Lycaon pictus). Positive seroconversion with no harmful side-effects was seen in all the animals. PMID- 1512878 TI - Prevalence of antibody titers to Leptospira spp. in Minnesota white-tailed deer. AB - Serum samples (n = 204) from 124 white-tailed deer (Odocoileus virginianus) in northeastern Minnesota (USA) were collected from 1984 through 1989 and tested for antibodies to six serovars of Leptospira interrogans (bratislava, canicola, grippotyphosa, hardjo, icterohemorrhagiae, and pomona) using a microtiter agglutination test. Eighty-eight (43%) sera were positive at greater than or equal to 1:100 for antibodies against serovars pomona and/or bratislava; none was positive for any of the other four serovars. None of the 31 sera collected in 1984-85 was positive, whereas all 54 sera collected from 1986 through 1988 had titers of greater than or equal to 1:100. During 1989, only 34 (29%) of 119 sera had titers of greater than or equal to 1:100. Based on these results, we believe there to be wide variability in exposure of Minnesota deer to Leptospira interrogans. PMID- 1512879 TI - Borrelia sp. in ticks recovered from white-tailed deer in Alabama. AB - Six hundred sixty-five hunter-killed white-tailed deer (Odocoileus virginianus) from 18 counties in Alabama (USA) were examined for ticks. Most of the collections were made at state-operated wildlife management areas. Four species of ticks (n = 4,527) were recovered: the lone star tick Amblyomma americanum (n = 482); the Gulf Coast tick A. maculatum (n = 11); the winter tick Dermacentor albipictus (n = 1,242); and the black-legged tick Ixodes scapularis (n = 2,792). Fifty-six percent of the ticks (n = 2,555) were examined for Borrelia sp. spirochetes using an immunofluorescent, polyclonal antibody assay. Spirochetes were detected in I. scapularis (five females, seven males) from Barbour, Butler, Coosa, and Lee counties and A. americanum (four males, four nymphs) from Hale, Lee, and Wilcox counties. Area-specific prevalences in ticks were as high as 3.3% for I. scapularis and 3.8% for A. americanum. PMID- 1512880 TI - The activity of ceftiofur sodium for Aeromonas spp. isolated from ornamental fish. AB - Our objective was to determine the activity of ceftiofur sodium against Aeromonas hydrophila and A. sobria isolated from a variety of domestic and imported tropical fish. Twelve antimicrobial drugs were tested for effectiveness against these aeromonads using the Kirby-Bauer Disk Diffusion technique and minimum inhibitory concentration determinations. Ceftiofur sodium was highly effective in vitro against aeromonads isolated from ornamental fish. Of the 42 isolates of Aeromonas spp. tested, none were resistant to ceftiofur sodium; however, all isolates were resistant to ampicillin, and 71% were resistant to tetracycline. PMID- 1512881 TI - Monthly incidence of Theileria cervi and seroconversion to Babesia odocoilei in white-tailed deer (Odocoileus virginianus) in Texas. AB - Monthly monitoring of fawns collected from an area in Texas endemic for Theileria cervi and Babesia odocoilei showed that transmission of T. cervi occurred during July and August, a time period consistent with the occurrence of Amblyomma americanum. Seroconversion to B. odocoilei occurred during October to December and possibly continued through January and February. The time of seroconversion was more suggestive of transmission of B. odocoilei by Ixodes scapularis than by Amblyomma americanum. PMID- 1512882 TI - Chaunocephalosis in a wild population of Asian open-billed storks in Thailand. AB - The most common trematode collected from Asian open-billed storks (Anastomus oscitans) was Chaunocephalus ferox (80% prevalence). The trematode was paired in granulomas in the intestinal wall. Based on histological examination of these capsules, there was degeneration and necrosis of muscle cells in the tunica muscularis. Granulation tissue with hetrophil and lymphocyte infiltration appeared in the granulomas. Intestinal villi were shorter and wider in infected areas than in non-infected areas. Some intestinal glands were dilated. Storks with high intensity of C. ferox appeared ill. The death of storks infected with C. ferox may result from malnutrition due to the loss of absorptive function of the intestine and from the effect of granuloma formation which might interfere with the intestinal peristalsis. PMID- 1512883 TI - Clinostomum complanatum (Trematoda: Clinostomatidae) in five new fish hosts in Japan. AB - Metacercariae of Clinostomum complanatum were found in six species of natural freshwater fishes collected at Koyama Pond in Tottori City of Tottori Prefecture, Japan. Five of these fish species are reported here as new records for second intermediate hosts of C. complanatum in Japan: the silver crucian carp (Carassius gibelio langsdorfi), the deepbodied crucian carp (Carassius cuvieri), the carp (Cyprinus carpio), the topmouth gudgeon (Pseudorasbora parva) and the rose bitterling (Rhodeus ocelatus). PMID- 1512884 TI - Natural infections of Clinostomum complanatum (Trematoda: Clinostomatidae) in wild herons and egrets, Tottori Prefecture, Japan. AB - Nycticorax nycticorax, Ardea cinerea, Egretta garzetta, and Egretta intermedia were naturally infected with Clinostomum complanatum (Trematoda: Clinostomatidae) among fourteen wild herons, seven wild egrets and one wild bittern evaluated at the Veterinary Hospital of Tottori University, Tottori, Japan. The latter three species of heron and egrets are reported for the first time as definitive hosts of this parasite in Japan. PMID- 1512885 TI - Experimental evaluation of mink and Apodemus speciosus in the Echinococcus multilocularis life-cycle in Hokkaido, Japan. AB - The epizootiological status of mink (Mustela vison) as definitive hosts and Apodemus speciosus as intermediate hosts in the transmission of Echinococcus multilocularis in Hokkaido, Japan, were evaluated by orally inoculating mink with protoscoleces, and A. speciosus with eggs of the cestode, respectively. No tapeworms were recovered from the alimentary tract of the mink, and no hydatid cysts were recovered from the viscera of the egg-inoculated A. speciosus. We conclude that mink and A. speciosus cannot serve as definitive hosts and intermediate hosts of E. multilocularis, respectively, in Hokkaido. PMID- 1512886 TI - Prevalence of Trichinella spiralis in black bears (Ursus americanus) from Newfoundland and Labrador, Canada. AB - Tongue and diaphragm samples from 158 black bears (Ursus americanus) from Newfoundland and Labrador were examined for Trichinella spiralis. No larvae were detected in samples from the island of Newfoundland but one animal from the Labrador samples was infected. The results of this and other studies suggest a lack of involvement of the black bear in a sylvatic cycle of T. spiralis in eastern Canada. PMID- 1512887 TI - Insects feeding on desert bighorn sheep, domestic rabbits, and Japanese quail in the Santa Rosa mountains of southern California. AB - Desert bighorn sheep (Ovis canadensis cremnobates), a domestic rabbit (Oryctolagus cuniculus), and Japanese quail (Coturnix japonica) were used as bait animals to collect blood-feeding flies in an area of active blue-tongue and epizootic hemorrhagic disease virus transmission. Precipitin tests were used to confirm the blood source where feasible. Eight species of Culicoides, members of the Leptoconops kerteszi group, Simulium spp., Anopheles franciscanus, and Stomoxys calcitrans were collected from the bighorn sheep. Feeding on the bighorn sheep by Culicoides brookmani (n = 25), C. variipennis (n = 6), C. cacticola (n = 1), and Simulium spp. (n = 3) was confirmed by precipitin testing. Primary species attacking the rabbit were C. brookmani, C. variipennis, and the L. kerteszi group. The quail were attacked primarily by members of the C. copiosus group and the L. kerteszi group. PMID- 1512889 TI - Parasites and condition of coexisting populations of white-tailed and exotic deer in south-central Texas. AB - We examined the parasites and physical condition of coexisting white-tailed deer (Odocoileus virginianus), axis deer (Axis axis), fallow deer (Dama dama), and sika deer (Cervus nippon) on the YO Ranch (Kerr County, Texas, USA) during December 1982 to January 1984. White-tailed deer harbored 12 species of parasites. Exotic deer were infected with nine species of parasites. All parasites recovered from exotic deer and white-tailed deer have been reported from white-tailed deer. Exotic deer had higher condition ratings than white tailed deer. PMID- 1512888 TI - Ectoparasites of the blackbuck antelope (Antilope cervicapra). AB - Fifty-two free-ranging blackbuck antelope (Antilope cervicapra) from Texas were examined for ectoparasites. Two species of sucking lice (Anoplura), one species of chewing louse (Mallophaga), one species of louse fly (Diptera), and three species of ticks (Acari) were found. This is the first report of the anoplurans Linognathus cervicaprae and L. pithodes from the Western Hemisphere. The southern deer ked (Lipoptena mazamae), the winter tick (Dermacentor albipictus), and the rabbit tick (Haemaphysalis leporispalustris) are reported from blackbuck for the first time. The lone star tick (Amblyomma americanum) and the mallophagan (Damalinia cornuta cornuta) were reported previously from blackbuck in Texas, the latter species under the name Tricholipeurus balanicus balanicus. PMID- 1512890 TI - A case of cleft palate in a Kuril seal (Phoca vitulina stejnegeri), from Hokkaido, Japan. AB - A male pup Kuril seal (Phoca vitulina stejnegeri) from Hokkaido, Japan, was observed with a unilateral and total cleft of the primary palate. Complications included a supernumerary tooth, hypoplasia and asymmetry of the face, and deformation of the eyeball and external auditory meatus. An accompanying pneumonia may have resulted from water flowing into the respiratory system due to imperfect closure of the nostril by the cleft. No other abnormalities were found. PMID- 1512891 TI - Freemartinism in a captive herd of Rocky Mountain bighorn sheep (Ovis canadensis). AB - Freemartinism in two animals from a captive herd of Rocky Mountain bighorn sheep (Ovis canadensis) at the Denver Zoological Gardens (Denver, Colorado, USA) is described. A young ewe had female external genitalia, a masculine appearance, and demonstrated male behavior as she matured. Another ewe with female external genitalia died as a yearling. Necropsy revealed a non-patent vagina and internal male genitalia. Both females were chimeric with karyotypes containing XX and XY sex chromosomes. PMID- 1512892 TI - Immobilization of giant Chacoan peccaries (Catagonus wagneri) with a tiletamine hydrochloride/zolazepam hydrochloride combination. AB - A tiletamine/zolazepam combination was used to immobilize 24 captive giant Chacoan peccaries (Catagonus wagneri) at a mean dosage rate of 2.18 mg/kg (SD = 0.46) of body weight, given intramuscularly. The mean induction time (the time from injection until recumbency) was 7.6 min (SD = 2.1). Standing time (the time from injection until the peccary stood without stimulation or assistance) ranged from 90 to 240 min. Tiletamine/zolazepam in combination was an effective and safe immunobilizing agent for giant Chacoan peccaries. PMID- 1512893 TI - Effects of capture on hematological values and plasma cortisol levels of free range koalas (Phascolarctos cinereus). AB - Eight free-range koalas (Phascolarctos cinereus) were captured on Kangaroo Island (South Australia) and later transported to the Adelaide Zoological Gardens. Blood samples were collected at the time of capture and at 6 hr, 24 hr and 7 days later. Routine hematological analyses were performed and plasma cortisol levels determined. Significant differences were observed between sampling times for erythrocyte numbers, hemoglobin concentrations, packed cell volumes, mean cell volumes, mean cell hemoglobin concentrations, numbers of leukocytes, neutrophils, lymphocytes and lymphocyte:neutrophil ratio (P less than 0.05). No significant differences were detected between sampling periods in the numbers of monocytes (P = 0.707), eosinophils (P = 0.174) or plasma cortisol levels (P = 0.192). PMID- 1512894 TI - Xylazine hydrochloride-ketamine hydrochloride immobilization of free-living red foxes (Vulpes vulpes) in Spain. AB - A combination of xylazine hydrochloride-ketamine hydrochloride was used to immobilize 83 wild red foxes (Vulpes vulpes) (15 pups and 68 adults) at Donana National Park (Spain). Mean ketamine hydrochloride doses were 17.1 mg/kg (SE = 1.53) and 12.3 mg/kg (SE = 0.4) for pups and adults, respectively, and mean xylazine hydrochloride doses for the same groups were 6.2 mg/kg (SE = 0.63) and 4.7 mg/kg (SE = 0.14), respectively. Mean induction times and first reaction times were 1.6 minutes and 22.5 minutes for pups and 3.8 minutes and 39.4 minutes for adults, respectively. Recommended doses for wild adult foxes of unknown weight are 75 mg of ketamine hydrochloride and 20 mg of xylazine hydrochloride. PMID- 1512895 TI - On capturing bighorn sheep. PMID- 1512896 TI - A piece of my mind. The intern's vein. PMID- 1512897 TI - New MRI techniques allow noninvasive peek inside the thinking human brain. PMID- 1512898 TI - From the Surgeon General, US Public Health Service. PMID- 1512899 TI - From the Centers for Disease Control. Participation in school physical education and selected dietary patterns among high school students--United States, 1991. PMID- 1512900 TI - From the Centers for Disease Control. Lizard-associated salmonellosis--Utah. PMID- 1512901 TI - Models of the physician-patient relationship. PMID- 1512902 TI - Models of the physician-patient relationship. PMID- 1512903 TI - Models of the physician-patient relationship. PMID- 1512904 TI - Models of the physician-patient relationship. PMID- 1512905 TI - Models of the physician-patient relationship. PMID- 1512907 TI - Screening for lung cancer has no proven utility. PMID- 1512906 TI - High red cell distribution width in alcoholics: not due to liver disease. PMID- 1512908 TI - The death of a baby: neither forgiven nor forgotten. PMID- 1512909 TI - The exclusion of the elderly and women from clinical trials in acute myocardial infarction. AB - OBJECTIVE: To determine the extent to which the elderly have been excluded from trials of drug therapies used in the treatment of acute myocardial infarction, to identify factors associated with such exclusions, and to explore the relationship between the exclusion of elderly and the representation of women. DATA SOURCES: We conducted a systematic search of the English-language literature from January 1960 through September 1991 to identify all relevant studies of specific pharmacotherapies employed in the treatment of acute myocardial infarction. To accomplish this, we searched MEDLINE, major cardiology textbooks, meta-analyses, reviews, editorials, and the bibliographies of all identified articles. STUDY SELECTION: Only trials in which patients were randomly allocated to receive a specific therapeutic regimen or a placebo or nonplacebo control regimen were included for review. DATA EXTRACTION: Studies were abstracted for year of publication, source of support, performance location, drug therapies to which patients were randomized, use of invasive diagnostic tests or therapeutic procedures, exclusion criteria, size and demographic characteristics of the randomized study population, and principal outcome measures. DATA SYNTHESIS: A total of 214 trials met inclusion criteria, involving 150,920 study subjects. Over 60% of trials excluded persons over the age of 75 years. Studies published after 1980 were more likely to have age-based exclusions compared with studies published before 1980 (adjusted odds ratio, 4.92; 95% confidence interval, 2.33 to 10.54). Trials of thrombolytic therapy involving an invasive procedure were more likely to exclude elderly patients compared with other studies (adjusted odds ratio, 2.45; 95% confidence interval, 1.10 to 5.47). Studies with age-based exclusions had a smaller percentage of women compared with those without such exclusions (18% vs 23%; P = .0002), with the mean age of the study population significantly associated with the proportion of women participants (P = .0001, R2 = .29). CONCLUSIONS: Age-based exclusions are frequently used in clinical trials of medications used in the treatment of acute myocardial infarction. Such exclusions limit the ability to generalize study findings to the patient population that experiences the most morbidity and mortality from acute myocardial infarction. PMID- 1512910 TI - A controlled evaluation of continuous passive motion in patients undergoing total knee arthroplasty. AB - OBJECTIVE: To evaluate the efficacy of continuous passive motion (CPM) in the postoperative management of patients undergoing total knee arthroplasty. DESIGN: A randomized controlled single-blind trial of CPM plus standardized rehabilitation vs standard rehabilitation alone. SETTING: A referral hospital for arthritis and musculoskeletal care. PATIENTS: Consecutive patients with end-stage osteoarthritis or rheumatoid arthritis undergoing primary total knee arthroplasty who had at least 90 degrees of passive knee flexion. One hundred fifty-four patients were eligible and 102 patients agreed to participate and were randomized. Ninety-three patients completed the study protocol. INTERVENTION: Continuous passive motion machines programmed for rate and specified arc of motion within 24 hours of surgery with range increased daily as tolerated with standardized rehabilitation program compared with standardized rehabilitation program alone. MAIN OUTCOME MEASURES: Primary outcomes were pain, active and passive knee range of motion, swelling (or circumference), quadriceps strength at postoperative day 7, as well as complications, length of stay, and active and passive range of motion and function at 6 weeks. RESULTS: Use of CPM increased active flexion and decreased swelling and the need for manipulations but did not significantly affect pain, active and passive extension, quadriceps strength, or length of hospital stay. At 6 weeks there were no differences between the two groups in either range of motion or function. In this series, use of CPM resulted in a net savings of $6764 over conventional rehabilitation in achieving these results. CONCLUSION: For the average patient undergoing total knee arthroplasty, CPM is more effective in improving range of motion, decreasing swelling, and reducing the need for manipulation than is conventional therapy and lowers cost. PMID- 1512911 TI - Changes in sequential coronary arteriograms and subsequent coronary events. Surgical Control of the Hyperlipidemias (POSCH) Group. AB - OBJECTIVE: Assessment of the relationship between changes in sequential coronary arteriograms and subsequent clinical coronary events. DESIGN: The Program on the Surgical Control of the Hyperlipidemias, a randomized secondary atherosclerosis intervention trial, obtained coronary arteriograms at baseline, 3, 5, and 7 or 10 years of follow-up. Assessments of changes between pairs of coronary arteriograms were made by two-member panels blinded to the patients' assigned treatment and to the temporal sequence of the films. The relationship of changes between the baseline and the 3-year follow-up arteriograms and subsequent clinical coronary events was examined. SETTING: Three university hospitals and one private primary care facility. PATIENTS: A total of 838 patients, with 417 patients randomized to the control group and 421 to the intervention group. Of all patients, 695 had baseline and 3-year arteriograms. INTERVENTION: The control group received American Heart Association Phase II diet instruction and the intervention group received identical dietary instruction plus a partial ileal bypass operation. MAIN OUTCOME MEASURE: The use of arteriographic changes as a predictor of subsequent clinical coronary events. RESULTS: Changes between the baseline and the 3-year coronary arteriographic overall disease assessment were significantly associated with subsequent overall and atherosclerotic coronary heart disease mortality (P less than .01). For the combined end point of atherosclerotic coronary heart disease mortality or confirmed nonfatal myocardial infarction, a significant relationship between the overall disease assessment and subsequent clinical events was found in the control group (P less than .0001) and in the surgery group (P = .04). For this combined end point, however, the control and the surgery groups were different with respect to clinical coronary events after 3 years, stratified by the baseline to 3-year overall disease assessment (P less than .001, unadjusted; P = .06, adjusted for 3-year clinical covariates). CONCLUSIONS: Coronary arteriographic changes can be used in atherosclerosis intervention trials as a limited surrogate end point for certain clinical coronary events. This relationship is statistically compelling for overall mortality and atherosclerotic coronary heart disease mortality. For an individual patient, changes in the severity of coronary atherosclerosis seen on sequential coronary arteriograms can serve as prognostic indicators for subsequent overall or atherosclerotic coronary heart disease mortality. PMID- 1512912 TI - Access to recombinant erythropoietin by Medicare-entitled dialysis patients in the first year after FDA approval. AB - OBJECTIVE: Examine access to recombinant human erythropoietin (rHuEPO) by dialysis-dependent end-stage renal disease (ESRD) patients during the first year after FDA approval for use in clinical practice and Medicare coverage. DESIGN: Longitudinal and cross-sectional claims data analyses. SETTING: All US providers of outpatient dialysis treatment. PATIENTS: 126,201 Medicare-entitled dialysis patients (approximately 93% of all US dialysis patients). OUTCOME MEASURES: Percentage of patients who received rHuEPO, odds of receiving rHuEPO according to patient characteristics, and cost of rHuEPO to Medicare. RESULTS: One year after FDA approval, 52% of all dialysis and 60% of in-center hemodialysis patients who regularly had Medicare-paid dialysis services received rHuEPO at a monthly cost to Medicare of $19 million (18% of Medicare ESRD outpatient expenditures and 6% of all ESRD program expenditures). Blacks were less likely than whites to receive rHuEPO (odds ratio, 0.88; 95% confidence interval, 0.86 to 0.91). Home peritoneal and hemodialysis patients were less likely than in-center hemodialysis patients to receive rHuEPO (odds ratios, 0.17 and 0.22, respectively; 95% confidence intervals, 0.16 to 0.17 and 0.20 to 0.24, respectively). Use of rHuEPO varied across geographic regions. The odds of receiving rHuEPO were lower for patients of male vs female sex, of ages 35 through 64 years vs less than 35 years and greater than 65 years, with a longer history of ESRD, with polycystic kidney disease vs other causes of ESRD, and receiving care in nonprofit vs for-profit facilities. First-month hematocrits were slightly higher (1.2 percentage points) for patients starting rHuEPO in the 12th month than in the first month after FDA approval. CONCLUSIONS: With prompt insurance coverage, the majority of Medicare entitled dialysis patients received rHuEPO following widespread availability. Factors that may not be related to clinical need (race, setting of care, and geography) possibly influenced early patient access. More attention should be paid to monitoring the appropriate use of high-cost biotechnologic therapy. PMID- 1512913 TI - Recovery, resterilization, and donation of unused surgical supplies. PMID- 1512914 TI - Increased incidence of silent ischemia after acute myocardial infarction. AB - OBJECTIVE: To determine the incidence of angina pectoris during induced myocardial ischemia in patients who have had thrombolytic therapy for acute myocardial infarction in comparison with patients with angina pectoris. DESIGN: During percutaneous transluminal coronary angioplasty, both study groups had coronary artery occlusion by the balloon dilatation catheter for 5 minutes. SETTING: A tertiary, cardiology referral center. PATIENTS: Twenty-five patients with angina pectoris who were undergoing angioplasty were compared with 30 patients having angioplasty 2 days after thrombolytic therapy for acute myocardial infarction. OUTCOMES: Development of angina pectoris during balloon occlusion of the coronary artery was the primary end point; the ischemic response and muscle viability were assessed using both surface and intracoronary electrocardiograms and pulmonary artery wedge pressure. RESULTS: During balloon occlusion 16 (64%) of 25 patients in the angina pectoris group developed angina. In contrast, nine (30%) of 30 patients in the thrombolysis group had angina pectoris during balloon occlusion of the infarct artery (P less than .01). The electrocardiographic response to ischemia and changes in pulmonary wedge pressure were similar in the two study groups. CONCLUSION: After thrombolytic therapy for myocardial infarction, silent ischemia may be the rule rather than the exception. PMID- 1512915 TI - Antiphospholipid antibody syndrome. PMID- 1512916 TI - Exclusion of the elderly and women from coronary trials. Is their quality of care compromised? PMID- 1512917 TI - Global health interdependence. A grass-roots approach. PMID- 1512918 TI - Treatment of tinnitus. PMID- 1512919 TI - [Japanese Circulation Society, 1990-1991. Abstract]. PMID- 1512920 TI - The effect of levofloxacin, an optically-active isomer of ofloxacin, on fecal microflora in human volunteers. AB - Following oral administration of levofloxacin (LVFX, (S)-(-)-Ofloxacin; formerly designated as DR-3355) at 200 mg per dose 3 times a day for 7 days to 6 healthy male volunteers, degrees of disturbance of the fecal microflora and fecal drug concentrations were examined. The total viable count remained unchanged during the study period due to the minimal change in the number of members of the family Bacteroidaceae, the most predominant organisms. Most of the aerobes including facultative anaerobes were suppressed by LVFX with only a slight increase in yeasts. In particular, the members of the family Enterobacteriaceae were reduced to below the detection limit on and after day 3 through the time of discontinuation of the drug in all subjects but one. Among the obligate anaerobes, peptostreptococci and bifidobacteria decreased or disappeared in some volunteers, but no significant changes were observed in other anaerobes. Neither Clostridium difficile nor its toxin D-1 was detected in any of the volunteers. No side effects attributable to the drug were observed. During administration, LVFX was detected in the feces at high concentrations which correlated well with the decrease of susceptible members of flora as well as to their detection rate. PMID- 1512921 TI - [A study on the concentrations of levofloxacin in the gallbladder tissue and bile of patients]. AB - Concentrations of levofloxacin (LVFX, DR-3355), optically active (-)-ofloxacin, in the gall-bladder tissue and bile were determined in patients, and the results were as follows: 1. A single dose of LVFX (100 mg) was administered orally to 6 patients with cholelithiasis about 2 to 3 hours before operation. The range in the gallbladder tissues was 0.34 to 1.59 micrograms/g, while the range in sera was 0.20 to 1.05 micrograms/ml. The ranges in the adipose tissues, gallbladder bile, and common duct bile were 0.07 to 0.26 micrograms/g, 1.8 to 12.2 micrograms/ml, and 1.4 to 5.8 micrograms/ml, respectively. 2. A single dose of LVFX (100 mg) was administered orally to 5 patients with indwelling T-tube. Concentrations of LVFX in excreted bile samples were 1.2 to 2.4 micrograms/ml, 1.3 to 3.5 micrograms/ml, and 1.3 to 2.4 micrograms/ml at 2 to 4, 4 to 6, and 6 to 12 hours after administration, respectively. Therefore, it appears that LVFX may be effective in biliary tract infections, because of its sustained high concentrations in biliary system. PMID- 1512922 TI - Efficacy of a new quinolone, levofloxacin in patients with surgical infections. AB - The pharmacokinetics and clinical efficacy of levofloxacin (LVFX, DR-3355), an optically pure S(-)-enantiomer of ofloxacin, were studied in patients after surgery. In the pharmacokinetic study, 4 patients undergoing bile drainage were given 2 100-mg tablets by mouth. Peak levels of LVFX were from 2.22 to 4.02 micrograms/ml of plasma at 2-4 hours after the oral administration, and from 7.5 to 11.3 micrograms/ml of bile at 2-6 hours. Forty-three patients with surgical infections, including 16 skin and soft-tissue infections and 12 wound infections, were treated with LVFX. Twenty-eight (70%) of the 40 patients whose results could be evaluated had excellent or good results; 42 (93%) of the 45 causative organisms identified were eradicated. An episode of diarrhea with chills and fever occurred in a 38-year-old man. The results suggested that LVFX has satisfactory antimicrobial effects in surgical infections. PMID- 1512923 TI - [Fundamental study on levofloxacin in the field of obstetrics and gynecology]. AB - We performed a fundamental study on levofloxacin (LVFX, DR-3355), a new synthetic antimicrobial agent, in the field of obstetrics and gynecology. Concentrations in serum and intrapelvic genital organs (various regions in the uterus, ovary and oviduct) were determined following single oral administration. The transport of LVFX into genital tissues was found to be good, with the tissue levels of 0.64 2.13 micrograms/g after oral administration of 100 mg and 0.77-4.86 micrograms/g after administration of 200 mg. These tissue levels of LVFX were higher than those in serum and exceeded the MIC90 values against most causative organisms isolated from the lesions of obstetric and gynecological infections. These data indicate that LVFX should be useful in the field of obstetrics and gynecology. PMID- 1512924 TI - [Pharmacokinetic and clinical evaluation of levofloxacin in obstetrics and gynecology]. AB - Levofloxacin (LVFX, DR-3355), a new synthetic quinolone derivative antibacterial agent, was evaluated for its pharmacokinetics and clinical efficacy in obstetric and gynecological infections, and the following results were obtained. Concentrations of LVFX in serum and intrapelvic genital organs such as uterine and adnexal tissues were determined following oral administration of 100 mg. Tissue penetration of LVFX was found to be good, with its tissue levels (Cmax) of 1.17-2.16 micrograms/ml or g after inhalation anaesthesia and 1.15-2.17 micrograms/ml or g after lumbar spinal anaesthesia. LVFX was given to 22 cases of obstetric and gynecological infections with a daily dose of 200-600 mg for 3-14 days and its clinical efficacy was 95% and bacteriological response was 100%. No side effect was observed. From these findings, we consider that LVFX will be a useful antibacterial agent against obstetric and gynecological infections. PMID- 1512925 TI - [Pharmacokinetic and clinical evaluation of levofloxacin in obstetrical and gynecological field]. AB - Levofloxacin (LVFX, DR-3355) a new synthetic antibacterial agent, was evaluated pharmacokinetic and clinically in the field of obstetrics and gynecology and the following results were obtained. 1. The transport of LVFX into genital tissues (various regions in the uterus, ovary and oviduct) after a single oral administration of 200 mg was found to be good. 2. Sixteen patients with genital infections (endometritis, salpingitis, cervicitis, mastitis) were treated with LVFX at daily doses of 200-300 mg for 5-15 days. The efficacy rate was 100% and no side effect was observed. PMID- 1512926 TI - [Pharmacokinetic, bacteriological, and clinical studies on panipenem/betamipron in children]. AB - Pharmacokinetic, bacteriological and clinical studies were performed on panipenem/betamipron (PAPM/BP) in children. The results are summarized as follow: 1. Twelve patients with various bacterial infectious diseases were treated with PAPM/BP. Each dose was 20 mg/20 mg/kg, administered 3 times daily, in 30-minute intravenous drip infusion. Treatments were continued for 5-22 days. Clinical efficacies of PAPM/BP in 12 patients with bacterial infections (1 with suspected sepsis, 5 with pneumonia, 1 with acute maxillary sinusitis, 2 with acute otitis media, 1 with cervical abscess and 2 with urinary tract infection complexed type) were evaluated as excellent in 7, good in 4 and fair in 1, with an efficacy rate of 91.7%. Seventeen causative organisms found in 10 patients (Haemophilus influenzae in 4, Branhamella catarrhalis in 3, Streptococcus pneumoniae in 2, Pseudomonas aeruginosa in 2, Staphylococcus aureus in 1, alpha-Streptococcus in 1, Corynebacterium sp. in 1, Peptostreptococcus micros in 1 and Klebsiella pneumoniae in 2) were eradicated except 2 strains (S. aureus and P. aeruginosa) from 1 patient (patient No. 2). No adverse reactions were observed in any of the 12 patients. 2. MICs of PAPM were examined against 22 clinical isolates (H. influenzae 5, B. catarrhalis 3, alpha-Streptococcus 3, S. pneumoniae 2, Corynebacterium sp. 2, S. aureus 1, P. aeruginosa 1, P. micros 1, Enterobacter cloacae 1, Escherichia coli 1, Group D Streptococcus 1 and Staphylococcus epidermidis 1) from children with bacterial infections. PAPM showed a good antibacterial activity comparable to the activity of cefoperazone (CPZ) against S. pneumoniae strains relatively tolerant to penicillins. However, the activity of PAPM against H. influenzae was somewhat weaker than that of CPZ. 3. Pharmacokinetic studies.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1512927 TI - [Clinical evaluation of panipenem/betamipron in children]. AB - Panipenem/betamipron (PAPM/BP), a new injectable carbapenem antibiotic, was evaluated for its safety and efficacy in children. Ninety three percentage (14 in 15 cases) of various infections were cured with PAPM/BP therapy. Transient skin rash occurred in 1 case, probably due to the histamine-like effect of PAPM/BP. The plasma half life of panipenem was 0.85 +/- 0.07 hours. PAPM/BP was evaluated to be a less-epileptogenic carbapenem antibiotic. PMID- 1512928 TI - [Studies on panipenem/betamipron in the pediatric field]. AB - Pharmacokinetic and clinical evaluations of panipenem/betamipron (PAPM/BP) were carried out in pediatric patients. The following results were obtained: 1. Upon 30-minute intravenous drip infusion at a dose of 20 mg/kg, plasma concentrations of PAPM/BP reached their peaks at the end of drip infusion with average values of 62.94/47.32 micrograms/ml, and their plasma half-lives were 1.00/0.51 hour in the beta-phase. Upon 30-minute intravenous drip infusion at a dose of 10 mg/kg, peak plasma concentrations were 32.10/23.76 micrograms/ml and plasma half-lives were 0.93/0.59 hour. 2. The urinary excretion rates of PAPM/BP after 30-minute intravenous infusion at doses of 20 and 10 mg/kg were 25.09/81.04% and 32.14/84.66%, respectively. 3. PAPM/BP was administered to 18 cases (upper and lower respiratory tract infections, pneumonia and urinary tract infections) at daily doses of 30-88.9 mg/kg/day divided into 3 dosages using 30-minute intravenous drip infusion. Clinical responses were "excellent" in 12 patients, "good" in 5, and "poor" in 1, hence an efficacy rate of 94.4% was obtained. 4. Bacteria identified from various diseases involved 11 strains of 6 species, and the eradication rate was 90.9%. 5. No side effect was recognized in any patient. Laboratory test results showed abnormalities in including 1 case with leukopenia, and in 2 cases with elevation of GOT and GPT. PMID- 1512929 TI - [Bacteriological and clinical studies of panipenem/betamipron in pediatrics]. AB - We carried out bacteriological and clinical studies of panipenem/betamipron (PAPM/BP), a newly-developed carbapenem antibiotic, in pediatrics, and the following results were obtained: 1. When antibacterial activities of panipenem (PAPM) were determined, it was found that MICs against such Gram-positive cocci as Staphylococcus aureus and Streptococcus pneumoniae and against such Gram negative rods as Escherichia coli, Haemophilus influenzae, Pseudomonas aeruginosa, and Branhamella catarrhalis were all sufficiently low. 2. PAPM showed better MIC-correlated antibacterial activities against 215 subcultured strains of methicillin-resistant S. aureus (MRSA) than imipenem. 3. Clinical efficacies were evaluated to be excellent in 23 of 34 patients treated with PAPM/BP, excluding 3 patients from the efficacy evaluation. In addition, good responses were obtained in 10 patients but poor response in one, showing the overall efficacy rate of 97.1%. As for bacteriological efficacies, the eradication rate was also determined to be high, 92.6%. 4. As for side effects, rash appeared in 2 patients, and soft stool and diarrhea occurred in one each. The overall incidence of side effects was calculated to be 10.8%. As for abnormal laboratory findings, increases of eosinophiles in 4 patients, thrombocytes in 2, total bilirubin in 1, and GOT in 1 were observed. From these results, PAPM/BP was thought to be a highly useful drug in pediatrics. PMID- 1512930 TI - [Pharmacokinetic and clinical studies on panipenem/betamipron in the pediatric field]. AB - Panipenem/betamipron (PAPM/BP), one of the carbapenems, was studied for its absorption and excretion, and clinical efficacy. The following is a summary of the results: 1. Absorption and excretion: Fourteen patients with their ages between 2 years and 14 years were administered with PAPM/BP 10 mg/kg, 20 mg/kg or 30 mg/kg, in 30-minute intravenous drip infusion. Maximum serum levels of PAPM, at dose levels of 10 mg/10 mg/kg, 20 mg/20 mg/kg and 30 mg/30 mg/kg of PAPM/BP, were 27.37 micrograms/ml, 59.3 micrograms/ml, 91.7 micrograms/ml, respectively, at the end of infusion. The half-lives of the 3 dose levels were all within 0.90 0.96 hour. Mean peak serum levels of BP, at dose levels of 10 mg/10 mg/kg, 20 mg/20 mg/kg and 30 mg/30 mg/kg, were 21.77 micrograms/ml, 35.29 micrograms/ml, 50.08 micrograms/ml, respectively, with half-lives of 0.55-0.63 hour. Urinary recovery rates of PAPM in the first 8 hours after administration at dose levels of 10 mg/10 mg/kg, 20 mg/20 mg/kg and 30 mg/30 mg/kg, were 15.9-31.1%, 15.3 36.9%, 11.0-40.5%, respectively, and those of BP during the same time were 33.1 79.1%, 41.3-93.4%, 12.9-94.4%, respectively. 2. CLINICAL RESULTS: Thirty-nine patients, including 2 with purulent meningitis, 1 with septicemia (suspect), 18 with acute pneumonia, 5 with bronchiolitis, 2 with tonsillitis (unable to receive oral antibiotics), 3 with cervical purulent lymphadenitis, 2 with bacterial enteritis, 6 with urinary tract infections were treated with PAPM/BP at dose levels of 30-100 mg/kg/day. Clinical responses in the patients were excellent or good. Even 2 patients with purulent meningitis were treated with PAPM/BP at dose levels of no less than 20 mg/kg x 3 and 33 mg/kg x 3. Most of respiratory and urinary tract infection cases of moderate severities were treated at dose levels of 30-60 mg/kg/day, i.e., 10 mg/kg x 3 or 20 mg/kg x 3. No adverse reaction was observed. One patient suffered from frequent watery diarrhea but the drug was continued to be administered and the patient recovered quickly. Abnormal laboratory findings were noted, in 2 cases with elevation of platelet, in 1 case with elevation of GOT, in 1 case with elevation of monocyte, in 1 with eosinophilia, in 1 with eosinophilia and decrease in platelet count, in 1 with eosinophilia and elevation of GOT and in 2 with elevation of GOT and GPT, but these abnormalities in the 9 cases were slight and transient. PMID- 1512931 TI - [A study on the disc sensitivity test for cefodizime]. AB - Susceptibilities of 289 strains of 34 bacterial species to cefodizime (CDZM) were determined using the 2-fold agar dilution method in parallel with the measurement of inhibition zone diameters in the single-disc method under the experimental conditions established by Kanazawa. The experiments demonstrated a significant correlation between MIC by the dilution method and diameter of inhibition zone in each of the conventional, overnight assay (about 16 hours incubation), thus the applicability of the single-disc assay for CDZM was established. Analysis of the data obtained using discs containing 30 micrograms of CDZM/disc revealed that the primary regression equation was in the form: D (Diameter, mm) = 32.3-13.5 log MIC (micrograms/ml) in the conventional assay for staphylococci, Enterococcus group and glucose-non-fermentative Gram-negative rods. For other bacteria, the primary regression equation was in the form: D (diameter, mm) = 24.1-8.4 log MIC (micrograms/ml) in the conventional assay. The range of variations in MICs estimated from diameters of inhibition zones in the disc test was then calculated in comparison with that in MIC determined by the 2-fold agar dilution test to estimate experimental errors which may be involved in the determination of MICs of CDZM using the single-disc assay. PMID- 1512932 TI - [Synergistic action of cefodizime and other antimicrobial agents on clinically isolated microorganisms. III. Synergistic action with gentamicin]. AB - An in vitro investigation was done on antimicrobial activities of cefodizime (CDZM) in combination with gentamicin (GM) against clinically isolated Gram negative rods. The results are summarized as follows. 1. Combined antimicrobial activities were dependent on antimicrobial activities of GM, similar to the CDZM + sisomicin (SISO) combination. The combined activities were concentration dependent, and they were more strongly dependent on GM concentrations than on CDZM concentrations. The obtained results suggested that synergistic or cooperative antimicrobial activities of the combination would be expected when GM concentrations in blood are at or somewhat lower than 1 MIC, and clinical activities would be exerted regardless of the presence of CDZM resistant organisms, similarly to CDZM+SISO combination. 2. It seems possible that, with regard to combinations of beta-lactam antibiotics and aminoglycoside antibiotics, there exist universal rules that combined activities are dependent on activities of aminoglycoside antibiotics, and that stronger concentration dependencies on aminoglycosides would be observed than those on beta-lactams. PMID- 1512933 TI - [Synergistic action of cefodizime and other antimicrobial agents on clinically isolated microorganisms. IV. Synergistic action with dibekacin]. AB - Antimicrobial activities of cefodizime (CDZM) in combination with dibekacin (DKB) were studied in vitro against clinically isolated Gram-negative rods. The results obtained are summarized as follows. 1. Similarly to combinations of CDZM+sisomicin (SISO) and CDZM+gentamicin (GM), combined activities of CDZM and DKB were dependent on antimicrobial activities of DKB, and the combined activities were more strongly dependent on DKB concentrations than on CDZM concentrations. The obtained results suggested that synergistic or cooperative antimicrobial activities of the combination would be expected when DKB concentrations in blood are at or somewhat lower than 1 MIC, and that clinical activities would be exerted regardless of the presence of CDZM resistant organisms, similarly to CDZM+GM combination. 2. As we have suggested previously, it seems possible that, with regard to combinations of beta-lactam antibiotics and aminoglycoside antibiotics, there exist universal rules that combined activities are dependent on activities of aminoglycoside antibiotics, and that stronger concentration dependencies on aminoglycosides would be observed than those on beta-lactams. PMID- 1512934 TI - [Clinical laboratory approach to evaluate efficacy of amikacin. Reevaluation of in vitro MIC break points in disc susceptibility test]. AB - Antimicrobial activities of amikacin (AMK) against 269 strains of various clinical isolates obtained in 1989 were determined and the reliability of the AMK disc susceptibility test in estimating approximate values of MICs was studied. In addition, clinical significance of various systems for the interpretation of the disc tests was evaluated to determine more useful method in the evaluation of clinical efficacy of AMK. Included in the study were a 3 category system of NCCLS, a 4 category system used in Japan, and the system proposed by the British Society for Antimicrobial chemotherapy. In this study, MICs were determined using the Mueller-Hinton agar containing 50 mg/L of Ca and 25 mg/L of Mg at an inoculum level of 10(3-4) CFU/ml. MIC80 values of AMK against Staphylococcus aureus and Staphylococcus epidermidis were 6.25 and 25 micrograms/ml, respectively. Those against Escherichia coli, Klebsiella pneumoniae, Proteus mirabilis, Proteus vulgaris, Enterobactor aerogenes, and Citrobacter spp. were less than 3.13 micrograms/ml. MIC values against Pseudomonas aeruginosa and Serratia marcescens were both less than or equal to 12.5 micrograms/ml. The disc susceptibility test was carried out according to the instruction in the Showa disc manual. Inhibition zones obtained with the disc method were compared with MIC values. The results of AMK disc susceptibility test obtained either with 30 micrograms discs or 10 micrograms discs were well correlated with MICs, indicating that the disc method was reliable in estimating approximate values of MICs (r = -0.807 to -0.897, P less than 0.01 in both instances). In the 4 category classification system currently used in Japan, the break points in MIC values of AMK proposed are (+3) MIC less than or equal to 3 micrograms/ml, (+2) MIC greater than 3-15 micrograms/ml, and (+) MIC greater than 15-60 micrograms/ml. The results obtained with Showa 30 micrograms discs and 30 micrograms discs prepared in this laboratory showed false positive results in 13% and 10.8% of the samples, and false negative results in 1.5% and 3.3%, respectively. In the 3 category classification system of NCCLS, the MIC break points proposed are defined sensitive (S) for MIC less than or equal to 16 micrograms/ml and resistant (R) for MIC greater than or equal to 32 micrograms/ml. In this study, the 30 micrograms disc tests using the above-mentioned 2 different types of discs resulted in false positive responses in 6.3% and 5.2% of the samples tested and false negative results in 1.1% and 1.9% of the samples, respectively.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1512935 TI - [Therapeutic efficacy of norfloxacin for experimental osteomyelitis in rabbits]. AB - Norfloxacin (NFLX), a new quinolone antibiotic agent, was evaluated for its efficacy in experimental osteomyelitis in rabbits. Osteomyelitis was induced in male rabbits by the inoculation of 10(7) CFU/ml (0.1 ml) of Staphylococcus aureus (MIC for NFLX: 0.78 micrograms/ml) with 0.4 ml of 3% sodium tetradecyl sulphate into the medullary cavity of the proximal tibia. The rabbits were divided into 3 different groups of 4 animals each. The animals in 2 groups were orally administered with NFLX; 100 mg/kg once-daily (group 2) and 50 mg/kg twice-daily (group 3) for 7 days from the 6th hour after inoculation. Group 1 was established as a control without administration of NFLX. All animals were sacrificed on the 7th day after inoculation. Acute osteomyelitic changes were found microscopically in all animals in group 1. In each of the 2 therapeutic groups, incidence of microscopic changes was 50% associated with remission of S-sialic acid value. Thus, NFLX may be considered a useful antimicrobial agent for the treatment of suppurative osteomyelitis. PMID- 1512936 TI - [Pharmacokinetics and clinical efficacy of ciprofloxacin in aged patients with chronic respiratory diseases]. AB - Pharmacokinetics and clinical efficacy of ciprofloxacin (CPFX) were investigated in aged patients with chronic respiratory diseases. Serum and sputum concentrations of CPFX were determined upon oral administration of 200 mg CPFX in 6 aged patients with chronic respiratory diseases (mean age = 78.8 +/- 3.2 years, 2 cases diagnosed chronic obstructive pulmonary disease with pneumonia, 3 cases were diagnosed bronchiectasis with acute exacerbation, and 1 case diagnosed chronic lung abscess). Maximal serum concentrations in these patients were 0.88 1.29 micrograms/ml (mean = 1.08 micrograms/ml). Thus, maximal serum concentrations of CPFX after oral administration in these aged patients were slightly lower than those in young subjects. However, peak sputum levels of CPFX following oral administration of 200 mg CPFX ranged from 0.53 to 1.47 micrograms/ml at 1-4 hours. These sputum concentrations of the 6 patients were sufficiently high for the inhibition of most infecting organisms in vitro. Clinical responses to CPFX in these 6 patients were good in 5, fair in 1, with an efficacy rate of 100%. Upon administration of CPFX, these 6 patients did not show any adverse reactions. These results suggest that oral administration of CPFX may keep effective levels in serum and sputum over 3 hours in aged patients with chronic respiratory diseases, and good clinical responses should be obtained without side effects in such patients. PMID- 1512937 TI - [Therapeutic effects of cefclidin against severe infections in patients with hematopoietic disorders. Hanshin Infection Study Group]. AB - One hundred thirty-eight patients with severe infections associated with hematopoietic disorders were treated with cefclidin (CFCL), and the efficacy and the safety of the drug were evaluated. The results obtained are summarized below. 1. Of the 126 patients in whom the efficacies were evaluable, 22 (17.5%) responded markedly well and 48 (38.1%) moderately, and the overall efficacy rate was 55.6%. 2. Efficacy rates for different infections were: 20.0% in septicemia, 61.2% in suspected septicemia, 46.7% in respiratory tract infection and 25.0% in others. 3. Significantly different efficacy ratings were observed between a group of patients with neutrophil counts of less than 100/mm3 and that with neutrophil counts of higher than 501/mm3. 4. Out of 138 patients in whom the safety was evaluable, side effects were observed in 5 patients (3.6%) and abnormal laboratory test values in 9 (6.5%). None was serious, however. PMID- 1512939 TI - [Clinical pharmacology and efficacy of levofloxacin in elderly patients]. AB - We studied a newly developed oral quinolone antimicrobial agent, levofloxacin (LVFX, DR-3355), and obtained the following results. 1. Serum and urine levels of LVFX were determined after oral administration of LVFX 100 mg to 11 elderly patients with various degrees of renal function insufficiencies. The patients were classified according to creatinine clearance (Ccr) values into Group I (n = 1, Ccr greater than or equal to 70 ml/min), Group II (n = 4, 40 less than or equal to Ccr less than 70 ml/min), and Group III (n = 6, Ccr less than 40 ml/min). The peak levels of LVFX did not differ greatly among the 3 groups, but in patients with severely impaired renal functions, serum concentrations decreased more slowly than in those with slightly and moderately impaired renal functions, and high serum levels were maintained over a long period. Urinary excretion of LVFX diminished in relation to degrees of renal failure. 2. LVFX was administered to treat 13 elderly patients with respiratory tract infections. Clinical responses were good in all patients with a high efficacy rate of 100%. Laboratory tests revealed eosinophilia in 1 case. The symptom was mild, however, and no severe side effects due to the drug were observed. PMID- 1512938 TI - [Clinical evaluation of ceftazidime monotherapy for infections complicated with hematological disorders]. AB - Fifty patients with infections associated with hematological disorders were treated with ceftazidime (CAZ). Among them 44 cases were evaluable, including 21 with acute leukemia, 17 with malignant lymphoma, and 6 with other hematological disorders. Excellent responses were observed in 15 patients (34.1%) and good responses in 15 (34.1%), with an overall efficacy rate of 68.2%. The efficacy rate among sepsis and suspected sepsis cases was 67.6%. This treatment was also effective in 7 of 10 cases in which neutrophil counts were less than 500/mm3 through the course of administration. Laboratory abnormalities included mild eosinophilia in 1 case, slight elevation of GOT in 1 case and slight elevation of GPT in 1 case. These results suggest that CAZ is an effective and safe antibiotics for the treatment of infections in patients with hematological disorders. PMID- 1512940 TI - [Sputum penetration of levofloxacin and its clinical efficacy in patients with chronic lower respiratory tract infections]. AB - Sputum penetration of levofloxacin (LVFX) was evaluated after a single oral dose of 100 mg or 200 mg to 4 patients with copious purulent sputa. The sputum concentration of LVFX reached maximum levels of 1.27 and 4.36 micrograms/ml at 4 hours, and still remained at concentrations of 0.32 and 1.68 micrograms/ml at 8 hours after administration of 100 mg and 200 mg, respectively. The AUC ratio of sputum/serum was 0.9-1.0, indicating good sputum penetration of LVFX in these patients. The clinical efficacy and the safety of LVFX were also evaluated in a total of 13 patients with respiratory tract infections associated with bronchiectasis, diffuse panbronchiolitis, etc. LVFX was administered orally at a daily dose of 200 mg once a day, 100 mg t.i.d. or 200 mg t.i.d. for 7-28 days (mean 14.7 days). The clinical response to the drug was rated as excellent in 1 case, good in 5, fair in 3, and poor in 2 cases in 11 evaluable cases, thus the efficacy rate was 54.5%. All the 3 strains of Haemophilus influenzae were eradicated. Of the 3 strains of Pseudomonas aeruginosa, eradication, decrease, and unchange was observed for 1 strain each. One strain of Streptococcus pneumoniae remained unchanged. No adverse reaction was observed except for 1 case with slight and temporary increase of eosinophils. The above results suggested that LVFX would be clinically useful in the treatment of chronic lower respiratory tract infections. PMID- 1512941 TI - [Laboratory and clinical studies on levofloxacin]. AB - A newly developed broad-spectrum fluoroquinolone, levofloxacin (LVFX, DR-3355), was evaluated in vitro and in vivo in comparison with ciprofloxacin (CPFX), ofloxacin (OFLX) and norfloxacin (NFLX). The results were as follows. 1. Antimicrobial activity Minimal inhibitory concentrations (MICs) against 480 clinical isolates including 16 different species were determined using the microbroth dilution method. LVFX showed excellent antimicrobial activities against Gram-positive and -negative bacteria. The MIC values of LVFX for Gram positive bacteria were superior to those of the other quinolones tested. The MIC values of LVFX for Gram-negative bacteria were comparable to those of CPFX and superior to those of OFLX and NFLX. 2. LVFX concentrations in serum and sputum LVFX was orally administered in a single dose of 200 mg to 2 patients with chronic lower respiratory tract infections, and its concentrations in serum and sputum were measured at intervals using bioassay. The peak concentrations of LVFX in serum were 1.52 and 1.24 micrograms/ml, and 84-95% of serum level were detected in sputum. From these data, it appeared that LVFX penetrate well into the lung. 3. Clinical efficacy and adverse reactions Fifteen patients with respiratory tract infections were treated with LVFX, and the overall efficacy rate was 78.6% (excellent in 3 cases, good in 8, fair in 3, poor in 0). As adverse reactions, anorexia was observed in 2 cases, diarrhea in 1 case and tremor of finger in 1 case. Although an elevation of total bilirubin in serum was observed in a case as an abnormal laboratory finding, it was mild, transient and improved rapidly after the completion of LVFX treatment. PMID- 1512943 TI - [Penetration of levofloxacin in bile]. AB - The penetration into bile of a new pyridonecarboxylic acid derivative, levofloxacin (LVFX), was studied in a closs-over method with ofloxacin (OFLX) as the control drug in 6 post-operative patients. The lengths of time to the maximum concentrations in bile and the total areas under the curves were both almost the same for these 2 compounds, although the maximum bile concentration of LVFX was slightly lower than that of OFLX. A stability test for LVFX in human bile revealed that over 95.4% of the initial amount was recovered up to 24 hours after commencement of incubation at a room temperature, thus the stability in bile was similar to that in water. The penetration of LVFX which possesses twice as strong antibacterial activities as OFLX was similar to that of OFLX, suggesting that LVFX is useful against bile duct infections. PMID- 1512942 TI - [Chemotherapy of biliary tract infections (XXXVII). Excretion into bile and gallbladder tissue levels of levofloxacin and its clinical effect in biliary tract infections]. AB - Evaluations were made on biliary excretion and penetration into the gallbladder tissue of levofloxacin (LVFX, DR-3355), a new quinolone antibacterial agent, and its clinical efficacy in biliary tract infections. 1. Gallbladder tissue concentrations and biliary concentrations of LVFX at 2-6 hours at oral administration of 100 mg were 0.58-1.99 micrograms/g and 0.49-5.63 micrograms/ml, respectively. These tissue and biliary levels are almost equal or somewhat higher than the serum levels (0.55-1.63 micrograms/ml) of the compound. 2. The concentrations of LVFX and optical isomer DR-3354 in the serum, gallbladder tissue, and bile were determined after a single or a concomitant administration of LVFX 100 mg and/or ofloxacin (OFLX) 100 to 200 mg. The concentration ratio of LVFX to DR-3354 paralleled with the ratio of the 2 compounds administrated. 3. At a dose of 100 mg, the glucuronide of LVFX in the common duct bile was detected at proportions between 0.9 and 36.0%. 4. A total of 11 patients with biliary tract infections, including 6 cholecystitis 3 cholangitis, and 1 each of cholecystocholangitis and liver abscess was treated with LVFX at 100-200 mg t.i.d. for 3-14 days. Clinical results were excellent or good in 8 cases and fair in 3 cases, resulting in an efficacy rate of 72.7%. 5. A side effect and an abnormal change in laboratory findings were observed in both 1 case each and they were both mild. It was concluded that LVFX showed good penetration to the biliary tract as does OFLX, and that it would be a useful oral agent for the treatment of biliary tract infections. PMID- 1512944 TI - [Levofloxacin in the field of dermatology]. AB - 1. Minimum inhibitory concentrations (MICs) of levofloxacin (LVFX, DR-3355), ofloxacin (OFLX), tosufloxacin (TFLX), norfloxacin (NFLX) were determined, with an inoculum size of 10(6) cfu/ml, against 122 strains of Staphylococcus aureus isolated from lesions of skin infections. LVFX showed most frequent MIC values of 0.20 micrograms/ml. OFLX, TFLX, and NFLX showed most frequent MIC values of 0.39 micrograms/ml, less than or equal to 0.05 micrograms/ml and 0.78 micrograms/ml, respectively. 2. Serum and skin levels of LVFX after oral administration (10 mg/kg, fasting) were determined in rats. Serum levels were 1.79, 1.29, 0.60, 0.43 and 0.18 micrograms/ml, and corresponding skin levels were 1.63, 1.77, 1.04, 0.87 and 0.64 micrograms/g (wet weight) at 0.5, 1, 2, 4 and 8 hours after administration (n = 5), respectively. 3. LVFX was used clinically in 43 cases at doses of 200-300 mg divided into 2 or 3 doses, and evaluated for final overall clinical efficacy in 41 cases. Cure was observed in 21 cases, remarkable improvement in 13 cases, improvement in 4 cases, unchanged in 1 case, aggravation in 1 case, and remarkable aggravation in 1 case. Diarrhea was observed in 2 cases, diffuse erythema with feverishness in 1 case and slight dyspnea in 1 case. Transient slight eosinophilia, elevation of Al-P, anemia and leukopenia were observed. PMID- 1512945 TI - [Levofloxacin in obstetrics and gynecology]. AB - We investigated the clinical efficacy and the safety of levofloxacin (LVFX, DR 3355) in obstetrical and gynecological infections and the following results were obtained. 1. Clinical efficacies were evaluated as excellent in 2 and good in 9 cases, hence the efficacy rate was 100%. 2. Bacteriologically, the eradication rate was 16/17 (94.1%). 3. No Side effects nor abnormal changes in laboratory test results were observed. These results indicated that LVFX was highly useful in the treatment of obstetrical and gynecological infections. PMID- 1512946 TI - [Combination of pharmacological and non-pharmacological therapies in hypertension]. PMID- 1512947 TI - [Adverse reaction of anti-hypertensive drugs on sexual function]. PMID- 1512948 TI - [Hypoperfusion syndrome (brain, heart) caused by antihypertensive agents]. PMID- 1512949 TI - [Non-pharmacological therapy of hypertension--an overview]. PMID- 1512950 TI - [The restriction of salt intake for therapy of essential hypertension]. PMID- 1512951 TI - [An outline of exercise therapy in essential hypertensives]. PMID- 1512952 TI - [Exercise prescription for physical training in hypertensive patients]. PMID- 1512953 TI - [The characteristics of the physical training for therapy of hypertension]. PMID- 1512954 TI - [Psychosomatic therapy of essential hypertension]. PMID- 1512955 TI - [Life guidance to essential hypertension]. PMID- 1512956 TI - [Goal of the blood pressure reduction in hypertensive patients]. PMID- 1512957 TI - [Disturbance of cerebral circulation complicated with hypertension]. PMID- 1512958 TI - [Therapy of hypokalemia associated with hypertension]. PMID- 1512959 TI - [Antihypertensive therapy of the patients with hyperlipidemia]. PMID- 1512960 TI - [The treatment of hypertension with hyperuricemia]. PMID- 1512961 TI - [Treatment of hypertension with liver damage]. PMID- 1512962 TI - [Definition of borderline hypertension]. PMID- 1512963 TI - [Epidemiological aspects and prognosis of borderline hypertension]. PMID- 1512964 TI - [Borderline hypertension as stroke reservists]. PMID- 1512965 TI - [Non-pharmacological treatment of borderline hypertension]. PMID- 1512966 TI - [Epidemiology of mild hypertension]. PMID- 1512967 TI - [Prognosis and factors predicting its prognosis in mild hypertension]. PMID- 1512968 TI - [Indication of antihypertensive drugs]. PMID- 1512969 TI - [Hypertension and exercise capacity]. PMID- 1512970 TI - [The variability of 24-hour blood pressure and the affecting factors]. PMID- 1512971 TI - [Nonpharmacological therapy of mild hypertension]. PMID- 1512972 TI - [Characteristics of hypertension in the elderly]. PMID- 1512973 TI - [Daily blood pressure variability in elderly hypertension]. PMID- 1512974 TI - [Circulatory regulatory function in elderly hypertension]. PMID- 1512975 TI - [Blood pressure response to exercise]. PMID- 1512976 TI - [Non-pharmacological therapy of hypertension in the elderly]. PMID- 1512977 TI - [White coat hypertension in the elderly]. PMID- 1512978 TI - [Silent cerebrovascular disease]. PMID- 1512979 TI - [Obesity and hypertension]. PMID- 1512980 TI - [Mechanisms of elevated blood pressure in obesity-related hypertension]. PMID- 1512981 TI - [Mechanism of blood pressure reduction during caloric reduction in obese hypertensives]. PMID- 1512982 TI - [High renin hypertension]. PMID- 1512983 TI - [Exercise hypertension]. PMID- 1512984 TI - [Malignant hypertension]. PMID- 1512985 TI - [Hypertensive emergencies]. PMID- 1512986 TI - [Salt-responder and non-responder: general concept]. PMID- 1512987 TI - [Role of intrarenal hemodynamics in sodium-sensitivity of blood pressure]. PMID- 1512988 TI - [Dopamine mechanisms in salt-responsive hypertension]. PMID- 1512989 TI - [Non-modulating essential hypertension]. PMID- 1512990 TI - [Lean hypertension]. PMID- 1512991 TI - [Patient compliance in the treatment of essential hypertension]. PMID- 1512992 TI - [Childhood hypertension]. PMID- 1512993 TI - [Hypertension in young adults]. PMID- 1512994 TI - [Economic evaluation of hypertension control program]. PMID- 1512995 TI - [Pre- and postoperative management of hypertension]. PMID- 1512996 TI - [Hypertension during anesthesia]. PMID- 1512997 TI - [Diurnal variations of blood pressure in shift workers]. PMID- 1512998 TI - [Pathophysiology of normotensive subjects with a family history of hypertension]. PMID- 1512999 TI - [Differential diagnosis of primary and secondary hypertension]. PMID- 1513000 TI - [Secondary hypertension due to tubulointerstitial nephritis]. PMID- 1513001 TI - [Gordon's syndrome]. PMID- 1513002 TI - [Solitary renal cyst and polycystic kidney associated with renal hypertension]. PMID- 1513003 TI - [Hypertension after renal transplantation]. PMID- 1513004 TI - [Reduction in drugs or dosage of antihypertensive treatment]. PMID- 1513005 TI - [Hypertension complicating renal trauma]. PMID- 1513006 TI - [Obstructive uropathy and hypertension]. PMID- 1513007 TI - [Circadian rhythms of blood pressure in renal hypertension]. PMID- 1513008 TI - [Renovascular hypertension: etiological classification and procedures for diagnosis]. PMID- 1513009 TI - [Circadian rhythms of blood pressure in renovascular hypertension]. PMID- 1513010 TI - [Pituitary hypertension]. PMID- 1513011 TI - [Hypertension in hyperparathyroidism]. PMID- 1513012 TI - [Antihypertensive agents and quality of life]. PMID- 1513013 TI - [Primary aldosteronism]. PMID- 1513014 TI - [Congenital adrenal hyperplasia]. PMID- 1513015 TI - [Pheochromocytoma]. PMID- 1513016 TI - [Secondary hypertension due to endothelin-producing tumor]. PMID- 1513017 TI - [Secondary hypertension due to renin-producing tumor]. PMID- 1513018 TI - [Hypertension due to cardiac and aortic diseases]. PMID- 1513019 TI - [Hypertension in pregnancy, preeclampsia]. PMID- 1513020 TI - [Drugs and other substances inducing hypertension]. PMID- 1513021 TI - [Resistant hypertension and treatment]. PMID- 1513022 TI - [Disease model of renal hypertension]. PMID- 1513023 TI - [Disease models of neurogenic hypertension]. PMID- 1513024 TI - [Disease models of steroid-induced hypertension]. PMID- 1513025 TI - [Antihypertensive drugs]. PMID- 1513026 TI - [How to overcome the side effects of antihypertensive agents]. PMID- 1513027 TI - [Abnormality of water and electrolyte metabolism due to antihypertensive agents]. PMID- 1513028 TI - [A study of comparison between Technicon THMS H-2 and Hematrak 590]. AB - Using 655 peripheral blood samples from normal individuals and patients, we evaluated the relationship between the measurements of red blood cell (RBC) and white blood cell (WBC) through the Hematrak 590 (Hematrak) and the generated flag systems in the Technicon H-2 (H-2). 1) Among the 12 VAR (Variation) flag positive samples in H-2, 10 samples were obtained from the patients receiving blood transfusions. The samples with high values of HDW (Hemoglobin distribution width) in H-2 seemed to have hypochromatic and polychromatic changes in RBC. 2) Hematrak is likely to be more sensitive than H-2 in discovering atypical lymphocytes (AL). When AL counts in Hematrak were over 5 or 6% of WBC, these results were coincident with ATYP flag positive in H-2. 3) In our examinations, when %Blast in H-2 was over 4%, BLASTS flag always generated positively. We think that H-2 is a tool with high reproducibility for the detection of the blast-like abnormal cells. 4) We evaluated the results of WBC differential count by the three methods of H-2, Hematrak and manual procedures in the peripheral blood samples from normal individuals. We recognized close correlations in neutrophils, lymphocytes and eosinophils (coefficients of correlation = 0.826-0.911), and relatively close ones in monocytes (r = 0.280-0.562), but no correlations in basophils (r = 0.106 0.281). To comprehend the pathophysiological states of the various diseases hematologically, it is necessary to understand the characteristics of the different measurement principles between the two instruments (H-2 and Hematrak). PMID- 1513029 TI - [Studies on the efficient application by STKS and 8200]. AB - We examined the usefulness of differential leukocyte counts provided by the automated STKS (Coulter) using the VCS method, the cell analyzer 8200 (Hitachi) using the image analysing as compared with that of the traditional manual method. In the STKS, about 8000 leukocytes can be counted within one minute and 5 part differential counts (neutrophils, eosinophils, monocytes, lymphocytes) are provided. The STKS may provided adequate identification of patients who have significant leukocyte abnormalities that require further study. Potential deficiencies of this system included an inability to detect abnormal lymphocytes such as ATL cells. In addition, low numbers of erythroblasts were missed, although these cells could be warned by a flagging system. In the cell analyzer 8200, the differential leukocyte count is done by the microscopic examination of stained blood films which is prepared by automatic device. Results from counts performed with this system correlated well with those obtained by the manual method. This system also missed low numbers of erythroblasts and ATL cells. Another potential deficiencies of the system is that number of cells observed within one minute were limited to about 100. When a prescribed set of cut-off limits, carefully chosen qualitatively, is introduced into these systems, automated leukocyte differential counts, with combination of STKS, 8200 and the manual method, clearly improve turn around time for laboratory blood assessments and this help to reduce unnecessary differential leukocyte counts by the manual method. PMID- 1513030 TI - [The clinicopathological evaluation of automated cytochemical hematology system (Technicon H1) in patients with leukemia and myelodysplastic syndrome]. AB - To determine the usefulness of the H1 system, we applied it to 14 patients with acute leukemia and 19 patients with myelodysplastic syndrome (MDS). We revealed interesting cytogram patterns in several patients with acute leukemia, ALL (L2), ALL (L3), and AML (M7). In the basophil and lobularity cytogram, their blast cells were clustered mainly in the blast box. However, a small cluster appeared in the basophil area and was expressed as pseudo-basophilia of 4.4%, 9.6%, and 21%, respectively. We speculated that not only normal basophils but also some type of leukemic blasts could be resistant to rupture of the cell membrane induced by a surfuctant at a low pH. Characteristics of H1 cytogram and histogram pattern have hardly been reported in patients with MDS. From the analysis of H1 pattern of 19 cases, we found that the (1) the values of RDW and HDW were high in comparison to those for aplastic anemia and normal controls and (2) the MPXI (mean peroxidase activity index) was significantly low at the time of diagnosis. MPXI had declined at the terminal stage in cases of death with bone marrow failure. These characteristics were concluded to be useful in clinicopathological diagnosis using the H1 automatic hematological system. PMID- 1513031 TI - [The correlation between hematopoietic status of the bone marrow and peripheral or marrow reticulocyte classification by using the automated reticulocyte analyzer Sysmex R-3000]. AB - In this study peripheral and marrow reticulocytes were counted by using the automated reticulocyte analyzer Sysmex R-3000 with the quick and accurate function of reticulocyte classification dependent on reticulocyte maturation. The correlation of reticulocyte count of the R-3000 to that of visual reticulocyte counting method was r = 0.926, y = 0.88x + 0.305 and r = 0.933, y = 1.32x + 0.328 for peripheral blood and bone marrow, respectively. The hematopoietic status of the bone marrow was reflected in peripheral reticulocytes better than in leukocytes or platelets. Moreover, at recovery stage from bone marrow suppression after chemotherapy, the ratio of immature type (HFR fraction) in peripheral reticulocytes increased to precede in several days increasing total reticulocytes. The relative reticulocyte counts in bone marrow was about 3 times higher than peripheral blood to be drawn at the same time higher and the patients suffering from megaloblastic anemia, MDS or DIC tended to have a much higher reticulocyte count in bone marrow than in peripheral blood. PMID- 1513032 TI - [Clinical application of data measured by automated blood cell counter]. AB - Rapid progress has been made in automated blood cell counting techniques using several kinds of apparatuses based on different mechanisms of measurement. We report a method of clinical application of the measurements made by an automated blood cell counter in the diagnosis and treatment of diseases, and discuss its usefulness, and its weaknesses that require improvement. PMID- 1513033 TI - [Transfusion medicine in near future]. PMID- 1513034 TI - [Anti-C100-3 antibody titration using 4-parameter logistic curve (results in its application to hepatitis C cases treated with interferon]. AB - We evaluated titers of C100-3 antibody by ELISA using a 4-parameter logistic fitting curve and examined the transition of the values in the cases of interferon treatment. The 4-parameter logistic fitting curve produced a standard curve in a wider range using a micro plate reader than the logarithmic curve. The values of C100-3 antibody during and after the treatments of interferon were changed in parallel with the alterations of ALT. The anti-C100-3 antibody titers assayed in the complete or partial responders were significantly reduced at the end of interferon therapy. These findings suggest the clinical usefulness of the evaluation of anti C100-3 antibody titers. PMID- 1513035 TI - [Detection of Campylobacter species by using polymerase chain reaction and nonradioactive labeled DNA probe]. AB - We have detected Campylobacter species which are now recognized as major pathogens of acute diarrheal disease in humans using polymerase chain reaction (PCR) and a nonradioactive labeled DNA probe. Diagnosis of Campylobacter enteritis without doing culture from stool samples is of great benefit in the laboratory. Two oligonucleotide primers (20 mer) complementary to a unique sequence of the DNA encoding ribosomal RNA (rRNA) of Campylobacter jejuni for PCR were synthesized by solid-phase phosphoamidite method. Amplified target DNA of 275 base pairs could be resolved on ethidium bromide-stained gels, and hybridized with an oligodeoxynucleotide probe (28 mer) conjugated to alkaline phosphatase. In identification experiments, it was shown that the nonradioactive probe was hybridized to clinical strains of C. jejuni (104), C. coli (5), C. laridis (5), C. hyointestinalis (1) and C. fetus subsp. fetus (1) with an accuracy of 99-100%, while it was not for Helicobacter pylori. Further, there was no evidence of amplification in strains of K. pneumoniae, S. marcescens and E. coli. Using direct detection to stool specimens, this method could be performed in C. jejuni in 39 of 43 culture-positive specimens (91%), and in 19 of 141 culture-negative specimens (13.5%), respectively. The results of this comparative study suggested that the DNA probe assay became a rapid and reliable technique to confirm culture of Campylobacter species. PMID- 1513036 TI - [Further evaluation of GPIb binding domain of vWf by synthetic peptides]. AB - We have already demonstrated that the GPIb binding domain of vWf resided at the regions corresponding to residues 474-488(G10) and 694-708(D5). Moreover, conformational change of vWf was suggested to be important for binding to GPIb. The effect of newly synthetized peptide combining G10 and D5 with lysin(G10-D5) on vWf binding to GPIb and platelet aggregation was studied. All synthetic peptides inhibited both vWf binding to GPIb, ristocetin-induced platelet aggregation and asialo vWf-induced platelet aggregation. G10-D5 possessed the most potent inhibitory activity in the interaction of vWf with GPIb. Only G10-D5 reacted with NMC-4 which recognized the epitope in appropriate conformation of vWf. These results indicate that G10-D5 retains some conformational structure and might be a good tool for anti-thrombotic agent. PMID- 1513037 TI - [Automated assay method for protein C anticoagulant activity]. AB - We developed an automated assay method for protein C anticoagulant activity to prolong the APTT measured with automated coagulation apparatus. The automated assay method required following three reagents. One was 0.025 mol/l calcium chloride solution. The other two were a protein C deficient plasma and a phospholipid plus protein C activator both of which constituted a recomposed protein C assay kit (BMY). 0-50% activities of protein C and clotting times were regressed on normal linear curve, while 25-150% activities and clotting times were regressed on logarithmic curve. The coefficients of variation were 2.9-3.4% (intra-assay) and 3.6-3.9% (inter-assay). A correlation of protein C activities between measured by automated assay method and by ordinary manual method was good (r = 0.954). Our data suggest that this automated assay is a useful method for measuring the protein C anticoagulant activities utilizing a coagulation apparatus. PMID- 1513038 TI - [Use of heart rate variability and pulse wave velocity for diagnosing cardiovascular autonomic neuropathy]. AB - Heart rate (HR) and arterial pulse wave velocity (PWV) were used for the evaluation of cardiovascular autonomic neuropathy. Data were analyzed from 30 patients with diabetes mellitus (aged from 13 to 75 years). Twenty healthy male subjects (aged from 22 to 44 years) were analyzed for computing normal values as well. After 15 minutes rest, electrocardiogram (ECG) of lead II and plethysmogram of finger tip were simultaneously recorded for each subject. The recording was first done in supine position for 120 seconds and subsequently in upright position for 40 seconds. HR was computed on the basis of consecutive pairs of R wave of the ECG. PWV was estimated by transit time from R wave peak to initial rise of pulse wave. Mean and coefficient of variation (CV) were obtained from the HR in the supine and upright positions respectively, and also from the PWVs. The influence of changing the position was evaluated by percentage of the difference (increasing rate). All the parameters were statistically tested for the difference between the patients with neuropathy and those without neuropathy. As the result, two parameters, that is, the CV of HR in the supine position and the increasing rate of PWV were found to be useful for diagnosing the cardiovascular autonomic neuropathy (p less than 0.05). PMID- 1513039 TI - [A case of C5 deficiency with polyarthritis]. AB - A 27-year-old female with polyarthritis was found to lack serum complement activity. Her serum CH50 was less than 1.9 U/ml. C5 protein in her serum was less than 2 mg/dl and its activity was not detected. The serum level of the other proteins of complement system examined were within the normal range. At 17 years old, she was diagnosed as rheumatic fever and was admitted to our hospital. She was treated with aminobenzylpenicillin and predonisolone for two months, and she was discharged from our hospital without any abnormalities. But she had no other episode of repeated infections. Family studies of this patient revealed that an elder sister of this patient was also homozygous deficiency of C5 and her parents were considered to be heterozygous deficiency of C5. From these results, the patient was considered to be inherited deficiency of C5. PMID- 1513040 TI - [Renal and neurologic symptoms due to cryoglobulinemia complicated with rheumatoid arthritis and Sjogren's syndrome]. AB - A 55-year-old woman with rheumatoid arthritis and Sjogren's syndrome developed complications of acute renal failure and symmetrical polyneuropathy. Laboratory examination revealed macroglobulinemia, positive cryoglobulin, and low complement levels. Kidney biopsy specimen revealed "thrombi" in glomerular capillary loops that were positive for PAS stain and negative for Congo red stain. Sural nerve biopsy specimens showed axonal degeneration and subsequent myelin loss due to vasculitis. We, therefore, diagnosed renal failure and polyneuropathy due to cryoglobulinemia, and treated the patient with double filtration plasmapheresis. Moreover, lymph node biopsy specimen revealed malignant lymphoma of the follicular, small-cell lymphoplasmocytic type which seemed to be related to the macroglobulinemia. The complication of cryoglobulinemia must be taken into consideration in patients with autoimmune disease or lymphoproliferative disorder complicated with renal or neurologic symptoms. PMID- 1513041 TI - [The clinical usefulness of the molar ratio of branched-chain amino acids to tyrosine (BTR) in discriminating stage of chronic liver diseases]. AB - We determined the molar ratio of branched-chain amino acids to tyrosine (BTR) in plasma and in serum by enzymatic method and compared it with Fischer ratio (the molar ratio of branched-chain amino acids to tyrosine and phenylalanine) in plasma obtained by conventional HPLC method. BTR in plasma and in serum was well correlated with plasma Fischer ratio. The normal range (mean +/- 2SD) of BTR was determined to be 4.41-10.05 in 210 normal subjects. In addition, we investigated the distribution of BTR values in patients with various liver diseases. BTR value decreased according to the severity of liver disease. We evaluated the clinical usefulness of BTR in patients with chronic liver diseases by cumulative distribution analysis (CDA) graph and receiver operating characteristic curve (ROC) analysis. The area under the curve for BTR analyzed by ROC for CH versus LC.HCC group was the highest (86.3%) of any for various concurrently-measured liver function tests, and was significantly higher than AST/ALT, ALT, AST, gamma GT (each, p less than 0.001) and ALB (p less than 0.05). These diagnostic results showed that BTR is a superior indicator in discriminating between liver cirrhosis and chronic hepatitis. PMID- 1513042 TI - [Microheterogeneity of serum glycoproteins in alcoholic liver disease]. AB - It has been reported that microheterogeneity (M-HT) of serum glycoproteins including transferrin is found in alcoholic liver disease (ALD). In the present study, M-HT of serum glycoproteins in ALD patients was analyzed using the Western blotting technique after isoelectric focusing. M-HT was found in serum alpha 1 antitrypsin, alpha 2-macroglobulin, ceruloplasmin, alpha 1-acid glycoprotein and hemopexin as well as transferrin, but not in serum prealbumin. M-HT disappeared following treatment with sialidase in one group of glycoproteins, but not in another group of glycoproteins. In hemopexin, M-HT was recognized only after treatment with sialidase. These results suggest that mechanisms of the appearance of M-HT of serum glycoproteins in ALD may differ. One mechanism is the interference of glycosylation of glycoproteins in the Golgi apparatus, and another is the decrease of asialo-protein receptors in hepatocytes. PMID- 1513043 TI - [Studies on the glucose tolerance and the endocrine function of the pancreas in primary sclerosing cholangitis]. AB - The responses of serum IRI, serum IRG, and blood sugar levels to 75 g oral glucose and serum IRI to glucagon injection were investigated in 26 chronic hepatitis, 20 liver cirrhosis, 5 primary sclerosing cholangitis (PSC) and 8 healthy volunteers served as controls. The results obtained herein were as follow: 1) The frequency of the glucose intolerance in PSC was higher than the other liver diseases. The mean values of the insulinogenic index (delta IRI/delta BS 30 min) in PSC was lower than control subjects. No suppression of IRG by glucose was observed in PSC. 2) The maximum IRI value (max delta IRI) in PSC during glucagon test was lower than that in control subjects. 3) In one case of 5 PSC ICSA was founded to be positive. These data suggest that we should pay much attention to suffering from diabetes mellitus in natural history of PSC. PMID- 1513044 TI - [Comparative study of extracorporeal shock wave lithotripsy (ESWL) between spark gap system and piezoelectric system]. AB - We have analyzed the results of the treatment given on 170 cases of cholecystolithiasis, using two different systems of ESWL: Spark Gap System (hereinafter SGS) and Piezoelectric System (hereinafter PES). 1) In the total cases, there were no significant differences in the fragmentation rate between the two systems. PES was, however, superior to SGS in terms of the complete stone free rate. On the other hand, SGS was superior to PES in terms of the average fragmentation rate. 2) We have classified cholecystolithiasis into 4 groups, combining CT and US. PES showed superiority in the ESWL Group 1 (seeming Pure Cholesterol Stone) and Group 2 (seemingly Mixed Stone) in terms of stone free rate. SGS showed superiority in ESWL Group 3 (seemingly Combination Stone) and Group 4 (seemingly Pigment Stone) in terms of fragmentation effect. 3) We have gained good results from both of the system according to Munich Criteria Modified. 4) Concerning the failures of fragmentation and insufficient stone free, further study shall be required to determine whether fragmentation should be repeated, the case should be handled as "beyond adaptability", or the two system-combined therapy should be applied. PMID- 1513045 TI - [A case of drug-induced allergic hepatitis by glycyrrhizin]. PMID- 1513046 TI - [Two cases of benign elevated lesions of the common bile duct]. PMID- 1513047 TI - [A case of common bile duct carcinoma with fully developed intestinal metaplasia]. PMID- 1513048 TI - [A case of acute hemorrhagic necrotizing pancreatitis in a renal allotransplanted patient improved by pericutaneous cyst drainage]. PMID- 1513049 TI - [An adult case of Reye like syndrome and acute pancreatitis associated with sodium valproate]. PMID- 1513050 TI - [New approach to evaluate duodenogastric reflux by color Doppler]. PMID- 1513051 TI - [Origins of the vagus nerve fibers to the rat intestine: tracing study with cholera-toxin B subunit as a retrograde tracer]. PMID- 1513052 TI - [Primary biliary cirrhosis and manganese-superoxide dismutase]. PMID- 1513053 TI - Individual and environmental characteristics related to influenza-like illness among children: a school-based case-control study. AB - To investigate individual and environmental characteristics associated with the manifestation of influenza-like illness (ILI), a survey enrolling 509 schoolchildren was conducted after an epidemic peak in the 1988/89 season, and then a case-control study was designed according to the information concerning illness onset and usual life-style. Case series were defined as those with fever greater than or equal to 38 degrees C due to acute respiratory illness, subsequent absenteeism and medical consultation during the epidemic peak; mild ILI (MILI; fever greater than or equal to 38 degrees C and less than 39 degrees C) and severe-ILI (SILI; fever greater than or equal to 39 degrees C). Control series were defined as those with no symptoms (NS) during the same period. An adjusted odds ratio (OR) was obtained using an unconditional logistic regression model for MILI (55) or SILI (33) and NS (204) groups among respondents (508). For MILI, increased risk was observed for easily inflamed tonsils (OR, 3.2; 95% CI, 1.6-6.4), with decreased risks for higher school grade (0.4, 0.2-0.8) and frequent intake of milk or dairy products (0.5, 0.3-1.0), but no significant association was determined for vaccination (0.6, 0.3-1.2). For SILI, there was an increased risk for easily inflamed tonsils (3.3, 1.4-7.9); and decreased risks for the higher grades (0.1, 0.1-0.3); use of a kerosene or gas heater with indoor exhaust (0.4, 0.2-0.9); and vaccination (0.3, 0.1-0.7). The OR of vaccinees for SILI constantly decreased regardless of grade and easily inflamed tonsils. PMID- 1513054 TI - [Seasonal variation of mean birth weight and births in Nagano Prefecture]. AB - Seasonal variation of mean birth weight in Nagano Prefecture was examined by a traditional time series analysis, which decomposes the variation in a series into trend, seasonal variation, other cyclic changes, and remaining irregular fluctuations, based on the data in Vital Statistics from January 1974 to December 1983. The seasonal index of mean birth weight showed a unimodal pattern with a peak in June for males, and a bimodal pattern with peaks in spring and autumn in females with statistical significance. Previous reports have revealed that gestational period is the most important factor associated with birth weight. Therefore, we carried out time series analysis for the mean gestational period and observed an apparent seasonal periodicity, which showed a unimodal pattern with a bottom in winter for both sexes and parities. According to the results of statistical testing of the degree of coincidence between two time series, the time series of mean birth weight and that of mean gestational periods showed statistically significant coincidences in their monthly variations for multiparae. On the other hand, mean birth weight at 40 gestational weeks, which reflects the intrauterine growth, did not show seasonality. These results suggest that seasonality in gestational periods might play an important role in creating seasonal variations of mean birth weight in Nagano Prefecture. The average daily number of births by month also showed apparent seasonalities both for primiparae and multiparae. Primiparae showed a bimodal pattern with peaks in February and August, while multiparae showed a unimodal pattern with a peak in May and a bottom in November. It has been said that the seasonality in marriage is one of important factors associated with seasonal variation in births.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1513055 TI - [The effects of long-term intake of a low concentration of sodium fluoride on bone loss in the growing senescence-accelerated mouse (SAM-P/6)]. AB - The long-term effects of low concentrations of sodium fluoride (0, 1 and 5 mg/l) in drinking water on bone metabolism were examined in the growing senescence accelerated mouse (SAM-P/6) as a spontaneous experimental model of senile osteoporosis. In 4 and 8 months of age respectively, there were almost no differences in body weight, and serum calcium, phosphorus and alkaline phosphatase levels between controls and fluoride groups. Calcium contents per dry weight of femoral bone were higher in fluoride groups than in controls. The bone mass of the trabecular was not affected by the low-concentration sodium fluoride intake. However, sodium fluoride decreased the rate of bone mass loss associated with aging in the cortical bone in SAM-P/6 compared with the control. The results of this study suggest that, in growing SAM-P/6 mice, a long-term low concentration sodium fluoride intake affects the skeletal metabolism. PMID- 1513056 TI - [Effects of repeated phase shifts in light-dark cycles on lipid metabolism in stroke-prone spontaneously hypertensive rats (SHRSP)]. AB - In the present paper, we employed the stroke-prone spontaneously hypertensive rat (SHRSP) as an animal model and the Kyo: Wistar rat (WKY) as a control, and studied on the effect of repeated phase shifts in light-dark cycles on lipid metabolism. First, we investigated diurnal rhythms of the lipid metabolism in SHRSP and WKY. In both strains, the activities of lipoprotein lipase (LPL) and hepatic microsomal cholesterol 7 alpha-hydroxylase in the dark period were significantly higher than those in the light period. In addition, in SHRSP, the serum apoA-IV level in the dark period was also higher than that in the light period. Next, we repeated the phase shifts in light-dark cycles twice a week with elongation of the light period for 4 weeks. LPL activity in the light period increased in response to the repeated phase shifts in both strains. This might be a defensive reaction to maintain homeostasis in the lipid metabolism in addition to energy production. Moreover, we performed repeated phase shifts in rats fed a high-fat and high-cholesterol diet containing 0.1% propylthiouracil to elucidate the effect on the development of hypercholesterolemia. The repeated phase shifts increased the levels of atherogenic lipoproteins and the atherogenic index (apoB/apoA-I). In particular, the effect was more marked in SHRSP. This deleterious effect could be due to the overproduction of very low density lipoprotein (VLDL, beta-VLDL) in the liver. PMID- 1513057 TI - [Quantitative evaluation of stress using the Type A behavior pattern]. AB - The problem of quantitative assessment of individual stress remains to be solved. The purpose of this study was to attempt to quantify the evaluation of stress using the Type A behavior pattern. A total of 1,101 factory workers, 602 male workers (aged 20-59) completed questionnaires regarding subjective symptoms, Type A behaviors, shift work, age, and lifestyles such as drinking habits and smoking habits. Using the results of our previous study, 3 component scores were calculated from the responses to 11 questions pertaining to the Type A behavior pattern. Stepwise logistic regression analysis of complaints of 8 stress-related subjective symptoms was performed, using shift work, age, drinking habits, and smoking habits as categorical independent variables, and 3 component scores as interval-scaled independent variables. The following conclusions were obtained. 1. The first component score, which represented overall irritability, was chosen as an independent variable for complaints of "hunger pains" and "tendency to have diarrhea." The first component score had a positive association with complaints of these stress-related subjective symptoms, and the association with "hunger pains" was statistically significant with P less than 0.05, though the association with "tendency to have diarrhea" was not significant. 2. The second component score, which represented relaxation, was chosen for complaints of "heartburn or gastric reflux" and "abnormal thirst." The second component score had a negative association with complaints of these stress-related subjective symptoms, and both associations were statistically significant with P less than 0.05.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1513058 TI - [Investigation of a new method for separation of neutrophils from a small volume of human blood]. AB - We have already reported a neutrophil separation method for the multiple simultaneous measurement of neutrophil chemiluminescence. However, when the reported separation method was used, at least 4 ml of venous blood was needed to collect enough neutrophils for chemiluminescent measurement. Because of this blood volume, there is a limitation on applications of the multiple simultaneous method for neonates, infants, and in some clinical situations. To expand the application of this neutrophil chemiluminescence measurement into clinical and health science areas, we have developed a new method for separation of neutrophils from a relatively small amount of blood (500 microliters). In addition, the influences of remaining red blood cells and hemoglobin levels in the neutrophil fraction on the chemiluminescence were examined to determine the necessity for elimination procedures. The new separation method used a capillary tube (length, 130 mm; outside diameter, 5 mm; thickness, 0.8 mm) with density gradient reagents (Histopaque 1077 and 1119). After centrifugal separation (500 g, 30 min), the neutrophil fraction was isolated with 93.1 +/- 4.7% purity and 60.6 +/- 11.1% yield. This purity and yield were comparable to or better than those with the previously reported method, while levels of remaining red blood cells and hemoglobin were about the same. Remaining red blood cells and hemoglobin in the neutrophil fraction acted on the chemiluminescence as a quencher. For the correct estimation of neutrophil chemiluminescence, elimination of remaining red blood cells and hemoglobin in the neutrophil fraction is necessary. This new neutrophil separation method is a very useful method, especially for cases in which available blood amounts are limited. PMID- 1513059 TI - [The effect of VDT polarity and target size on pupil area]. PMID- 1513060 TI - Survival rate and risk factors for patients with retinoblastoma in Japan. The Committee for the National Registry of Retinoblastoma. AB - Clinical, pathological and follow-up data on the 1,147 cases of retinoblastoma registered in Japan from 1975 to 1982 were statistically analyzed. The cumulative survival rate of the total 1,147 cases was 93.0% at 5 years and 90.3% at 10 years, calculated by the Kaplan-Meier method. The survival rate for the 757 unilateral cases was 93.3% at 5 years and 92.3% at 10 years. For the 390 bilateral cases, however, the rate was 92.2% at 5 years and 86.7% at 10 years. The Cox multivariate analysis indicated that, among the various clinical and pathological findings in the patients, extraocular invasion by the tumor was the most significant risk factor which is predictive of death due to tumor. The survival rate for patients with extraocular invasion was significantly better in cases undergoing subsequent local radiation and/or systemic chemotherapy than in cases without such aftercare. The cumulative incidence rate of second neoplasms in 409 cases of hereditary retinoblastoma was 4.8% at 10 years, 9.8% at 15 years and 15.7% at 20 years. The occurrence of a second neoplasm was the main cause of death in the hereditary cases 10 years after the first onset. PMID- 1513061 TI - Japanese family with blue cone monochromatism. AB - The diagnosis of blue cone monochromatism (BCM) is based on severely affected color vision with preserved blue function, nearly nonrecordable photopic ERG, and a family pedigree compatible with X-linked inheritance. We have studied the color vision and ocular function of three members of a family with BCM and a female carrier in the same family. Two of the three affected family members, 9- and 7 year-old brothers, showed the unique features of BCM in their color vision and ERG. The third affected family member, a 43-year-old uncle, showed achromatic vision. He had diabetic retinopathy and moderate cataract which were thought to disturb his blue cone function, causing apparent rod monochromatism. The female carrier, the mother of the brothers, showed normal visual functions except for a slight reduction in photopic ERG amplitude. We believe that this is the first description of BCM in a Japanese family. PMID- 1513062 TI - Vitreoretinal surgical technique for transplanting retinal pigment epithelium in rabbit retina. AB - Transplantation of retinal pigment epithelial (RPE) cells has been proposed as a potential remedial procedure for previously untreatable retinal diseases. In this study, a vitreoretinal surgical technique was used to transplant pigmented RPE cells obtained from pigmented rabbits into the subretinal space of New Zealand White rabbits. At the time the animals were sacrificed, the retina was re attached in all but 4 of the 24 experimental eyes. Histologically, by one week the transplanted RPE cells had formed a monolayer in patchy areas beneath the attached retina. By electron microscopy, RPE cells with prominent melanin granules were found attached to Bruch's membrane. Three weeks after transplantation, grafted RPE cells had formed apical microvilli and tight junctions with adjacent cells. The nucleus of the cells containing pigment had become oval, and their contact with Bruch's membrane appeared to be composed of bsal infoldings that were well formed. Our findings demonstrated the functional appearance of the transplanted RPE cells. PMID- 1513063 TI - Postoperative subconjunctival 5-fluorouracil injections and success probability of trabeculectomy in Japanese: results of 5-year follow-up. AB - The effects of postoperative subconjunctival 5-fluorouracil (5-FU) injections on the surgical outcome of trabeculectomy in the Japanese were studied in a total of 362 eyes of 263 glaucoma patients with the postoperative follow-up of 1-9 years. The probability of successful intraocular pressure (IOP) control at the 5-year point of the continuing follow-up was calculated by the life-table method of Kaplan-Meier. The eyes that had undergone trabeculectomy with postoperative injections of 5-FU (5-FU group) included 165 eyes with primary open-angle glaucoma (POAG), 38 eyes with secondary glaucoma (SG) and 60 eyes with refractory glaucoma. The eyes that had undergone trabeculectomy without postoperative 5-FU (control group) included 46 eyes with POAG, 31 eyes with SG and 22 eyes with refractory glaucoma. The surgical techniques and postoperative care were virtually identical between the two groups, except that the control group did not receive the postoperative 5-FU. The total amount of 5-FU given to each case averaged 36.5, 36.0 and 49.5 mg for POAG, SG and refractory glaucoma, respectively. At the 5-year follow-up point, the probability of maintaining IOP control below 21 mmHg with or without medication in the 5-FU group was 92.5% for POAG, 87.4% for SG and 57.5% for refractory glaucoma; while without medication the probability was 58.2, 54.8 and 27.8%, respectively. The probability of IOP control below 16 mmHg with or without medication in the 5-FU group was 77.9% for POAG, 66.8% for SG and 26.9% for refractory glaucoma; without medication the probability was 55.2, 49.8 and 24.5%, respectively. In the control group, the corresponding probability for each type of glaucoma was much lower than that in the 5-FU group, and the probability for IOP control below 16 mmHG was 0.12% at the 5-year follow-up point. In the 5-FU group, the mean postoperative IOP in successfully treated eyes remained at about 12 mmHg throughout the first 5 years of the follow-up period. There was no significant difference in incidence of postoperative complications between the 5-FU and control groups, except that corneal epithelial defect was noted in 38.8% of the eyes in the 5-FU group. No late complications related to the use of postoperative 5-FU were observed.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1513064 TI - Morphological and histochemical studies of goblet cells in developing human conjunctiva. AB - This study deals with the development of the human conjunctival goblet cells. Fifty-six eyes of human embryos and fetuses ranging from 5 to 41 weeks of gestational stage were used. The distribution of glycosaminoglycans in the goblet cells was investigated with 1% alcian blue (pH 2.5) staining. For identifying the types of glycosaminoglycans, enzyme digestion methods were carried out with streptomyces hyaluronidase, chondroitinase AC, chondroitinase ABC, or sialidase (neuraminidase). At 9 weeks of gestational age, goblet cells appeared in the fornix region of the conjunctiva and extended toward the palpebral and bulbar regions. Histochemical studies with enzyme digestion methods revealed the existence of sialomucin in the goblet cells from 9 weeks. This finding suggested that the goblet cells first appeared in the fornix area, extending toward the palpebral region, then toward the bulbar region, and containing sialomucin from their early stage of development. PMID- 1513065 TI - Phagocytosis and fibronectin of cells observed on intraocular lenses. AB - The phagocytic activity and distribution of fibronectin in the cells adhering to implanted intraocular lenses (IOLs) were studied in rabbits. IOLs were explanted from the posterior chamber 7 days after implantation. Phagocytosis by the cells from the IOLs was studied by electron microscopy after incubation with polystyrene beads. The distribution of fibronectin was examined immunohistochemically using an anti-fibronectin antibody. Many presumed macrophages and giant cells which were thought to be of macrophagic origin were observed on the IOLs. Adherence of the beads to the surface of the cells, phagocytosis of these beads, and fibronectin immunoreactivity were prominent in these presumed macrophages, whereas giant cells displayed a reduction in these activities. These findings suggest that the adherence activities of the presumed macrophages are less after giant cells are formed, reflecting a reduced production of fibronectin. PMID- 1513066 TI - Type of arteriovenous crossing at site of branch retinal vein occlusion. AB - A retrospective study of 63 patients (64 eyes) with symptomatic branch retinal vein occlusion, 30 men and 33 women, was carried out in this study. The ages of the subjects ranged from 40 to 82 years. Systemic hypertension was present in 41 patients and diabetes mellitus in 19. The occlusion involved the superotemporal vein in 39 eyes, inferotemporal vein in 20, superonasal vein in 2 or macular vein in 3. The site of the occlusion could be examined in detail in 57 eyes, and an arterial overcrossing was involved in 53 of these eyes (93%). This incidence of arterial overcrossing was significantly higher in the branch retinal vein occlusion eyes than in control eyes (P less than 0.05). PMID- 1513067 TI - Nonfamilial and unusual cases of Leber's hereditary optic neuropathy identified by mitochondrial DNA analysis. AB - Peripheral blood mitochondrial DNA (mtDNA) samples from 11 patients with acute optic neuritis or insidious optic atrophy were examined for the mutation at nt 11778 and nt 3460 in polymerase chain reaction products. The mtDNA mutation at nt 11778 was evident in 8 cases, which led to a definite diagnosis of Leber's hereditary optic neuropathy (LHON); 4 of the cases were familial and the remaining 4 cases were nonfamilial. None of the 11 patients showed the nt 3460 mutation. The symptoms and signs were variable among the LHON cases with nt 11778 mutation. Assessment of mtDNA provides a useful diagnostic aid for clinically undefined, seemingly nonfamilial or atypical cases of Leber's hereditary optic neuropathy, particularly in bilateral, insidious optic nerve disease in early childhood. PMID- 1513068 TI - Orbital extension of sinus lymphoma in AIDS patient. AB - A case of a 27-year-old white male with acquired immunodeficiency syndrome (AIDS) who had a maxillary sinus tumor with secondary orbital involvement was reported. Marked proptosis and distortion of the globe were present. Biopsy by the Caldwell Luc approach disclosed an immunoblastic lymphoma of B-cell origin. To the best of our knowledge, this is the first reported case of a maxillary sinus lymphoma extending into the orbit in a patient with AIDS. PMID- 1513069 TI - A case of endogenous Enterococcus faecalis endophthalmitis. AB - A case of successful treatment by vitrectomy and lensectomy of early-stage endogenous endophthalmitis caused by Enterococcus faecalis was reported. The case was a 50-year-old man with poorly controlled diabetes. Following T-tube drainage for a necrotic cholecystitis operation, he developed iridocyclitis in both eyes as well as fever. At the time of his first visit to our clinic, his right eye had already lost light perception. His left eye had visual acuity recognizing hand movement, marked uveitis, complicated cataract, and dense vitreous opacity. As gram-positive cocci were isolated from the aspirated vitreous, lensectomy and vitrectomy under irrigation with antibiotics were conducted. After the administration of systemic postoperative antibiotics and human immunoglobulin, the patient showed remarkable improvement in the state of his ocular fundus. By 60 days after the surgery, the visual acuity of his left eye recovered to 0.2. Endogenous Enterococcus faecalis endophthalmitis has rarely been reported in Japan. The diagnosis and treatment of this disease with reference to the above findings were discussed. PMID- 1513070 TI - The process of subretinal strand formation. AB - Surgically resected subretinal proliferative tissue (SRP) in proliferative vitreoretinopathy was examined by morphological and immunohistochemical methods. Membranous and strand-like SRPs were observed. Membranous SRP (4 cases) consisted of retinal pigment epithelial cells (RPEs) and a thin layer of extracellular materials. Strand-like SRP (14 cases) had a core, in which the proliferated cells were embedded among extracellular materials. RPEs and glial cells were found on the surface of the core. Immunohistochemical investigation revealed that the predominant cell components of the strand-like SRPs were RPEs and Muller cells, whereas membranous SRPs were composed mainly of RPEs. It was found that the majority of membranous and strand-like SRPs contained types I, III and IV collagens and fibronectin in the extracellular space. Based on the results of this study, a hypothetical process for the formation of SRP tissues was proposed. PMID- 1513071 TI - Attenuation of dysfunction in the ischemia-reperfused liver by glycyrrhizin. AB - The present study evaluated the effect of glycyrrhizin (GR) on an injury of the liver caused by ischemia-reperfusion in rats. In the liver ischemia-reperfusion model, levels of serum GOT, GPT and LDH activities and lipid peroxides in the liver tissue were significantly increased. On the contrary, total glutathione content in the liver tissue and NADPH cytochrome P-450 reductase activity of liver microsomes were decreased. Pretreatment with GR 20 mg/kg, i.v. 10 min before induction of ischemia resulted in significant decreases in serum GOT, GPT, LDH activities and the lipid peroxide level and a higher tissue glutathione content during the period of reperfusion. Electron microscopic studies revealed various hepatocellular damages with an almost intact sinusoidal endothelium in ischemia-reperfused livers. However, the degree of damage was less severe in the livers from the rats pretreated with 20 mg/kg GR. The results indicate that GR is able to provide partial protection against ischemia-reperfused damage. PMID- 1513072 TI - Comparison of contractile mechanisms by carbachol and ATP in detrusor strips of rabbit urinary bladder. AB - Contractile mechanisms by carbachol and ATP were compared in the detrusor strips of rabbit bladder. To exclude modulation of the agonists-induced responses by intramurally synthesized prostaglandins, all the experiments were done in the presence of the potent cyclooxygenase inhibitor flurbiprofen (1 microM). The concentration-response curves for carbachol and ATP were shifted to the right by 6- 10-fold by verapamil (10 microM), which abolished the K-induced contraction of the atropinized detrusor completely. A similar curve for carbachol was obtained in the absence of extracellular Ca [(Ca)o], but the contraction by ATP below 1 mM was more reduced by (Ca)o-depletion than by verapamil. Under Ca-free conditions, repeated applications of ATP resulted in no response, but those of carbachol induced reproducible contractions. These results suggest that carbachol and ATP induces Ca-influx through L-type Ca channels and releases Ca from the Ca stores. However, while carbachol might increase the sensitivity of contractile machinery to Ca on the one hand, ATP would open additional, verapamil-insensitive Ca channels. PMID- 1513073 TI - Antagonism of platelet-activating factor-induced increase in cytosolic free calcium concentration in human endothelial cells. AB - The effects of platelet-activating factor (PAF) antagonists on the agonist induced increase in cytosolic free calcium concentration, [Ca2+]i, in human vascular endothelial cells grown in monolayer were investigated by a continuous superfusion technique using a calcium fluorescent probe, fura-2. PAF caused a small but dose-dependent increase in [Ca2+]i. Seven structurally dissimilar PAF antagonists dose-dependently suppressed the peak response, among which WEB 2086 was the most potent, followed by WEB 2170 greater than FR 900452 not equal to ONO 6240 greater than BN 52021 not equal to kadsurenone not equal to CV 3988. These antagonists except for CV 3988 were specific for PAF, since they had no effects on calcium mobilization induced by thrombin or histamine, while CV 3988 had a non specific effect. PAF in the same range of concentration increased prostacyclin release from human endothelial cells. WEB 2086 also inhibited the PAF-induced prostacyclin release, while it had not effect on the release induced by histamine and thrombin. These results demonstrate the specificity and dose-response characteristics of PAF antagonists in cultured human endothelial cells and suggest that a PAF antagonist could be a valuable therapeutic agent in certain human diseases where PAF activation of endothelial cells may have a critical role. PMID- 1513074 TI - Pharmacological studies on lappaconitine: possible interaction with endogenous noradrenergic and serotonergic pathways to induce antinociception. AB - Systemic and intracerebroventricular (i.c.v.) injections of lappaconitine (LA) produced a dose-dependent inhibition of the response to thermal stimulation in sham-operated mice as assayed by the tail-immersion test. After spinal transection, the antinociceptive potencies of s.c.- or i.c.v.-administered LA were markedly reduced. Antinociception induced by systemically administered LA was clearly reduced by pretreatment with 6-hydroxydopamine or 5,7 dihydroxytryptamine through the i.c.v. and intrathecal (i.t.) routes. When LA was administered by i.c.v.-injection, the LA-induced antinociception was reduced by pretreatment with timolol, a beta-adrenergic antagonist, and ketanserin, a 5-HT2 antagonist. Administration of LA by the i.t. route resulted in a significant antinociceptive activity, which was also reduced by pretreatment with phenoxybenzamine, an alpha-adrenergic antagonist, and mianserin, a 5-HT1 antagonist. The results of these studies suggest that the central noradrenergic and serotonergic systems may be involved in the antinociception of systemically administered LA, and these pathways are mediated by beta-adrenoceptors and 5-HT2 receptors in the brain and alpha-adrenoceptors and 5-HT1 receptors in the spinal cord. PMID- 1513075 TI - Difference between halothane and barbiturate anesthesia in the influence of cerebral ischemia on the vagal baroreflex in dogs. AB - In halothane-anesthetized dogs, a decrease in baroreflex sensitivity (BRS) of approximately 20% was observed during the reperfusion period following 5-min global cerebral ischemia. When compared with our previous study on animals under pentobarbital anesthesia, the extent of the decrease in BRS was smaller and apparently more severe ischemia was necessary to damage the vagal component of the baroreflex. Substitution of halothane with pentobarbital during the reperfusion period failed to affect either BRS or the ratio of the vagal component. In another group, pre- and post-ischemic measurements of BRS was performed under halothane anesthesia, but the ischemic insult was given under thiopental anesthesia. In these animals, the extent of decrease in BRS (about 50%) was greater than that in animals subjected to ischemia under halothane anesthesia. The present results suggest that the anesthetics used during the ischemic insult may affect the extent of post-ischemic dysfunction of the baroreflex. The vagal component of the baroreflex may be more resistant to ischemia under halothane anesthesia than under barbiturate anesthesia. PMID- 1513076 TI - Novel derivatives of 5-fluorouridine and 5-fluorouracil having potent antitumor and lower immunosuppressive activities. AB - We studied the biological activities of several 5-fluorouridine (5-FUR) and 5 fluorouracil (5-FU) derivatives to find novel antitumor drugs with lower immunosuppressive effects. We examined 5-FUR and 5-FU derivatives acylated with (2-n-propyl-n-pentanoyl)glycine (KN-539). Among the examined compounds, we found satisfactory activities in a derivative of 5-FUR, 2',3',5'-tris-O-[N-(2-n-propyl n-pentanoyl)glycyl]-5-fluorouridine (UK-21), and a derivative of 5-FU, 1-(6-[N-(2 n-propyl-n-pentanoyl)glycyl] amino-n-hexylcarbamoyl)-5-fluorouracil (UK-25). UK 21 (0.05-0.2 mmole/kg, p.o., 10 days) and UK-25 (0.1-0.4 mmole/kg, p.o., 10 days) suppressed Meth A and E.L.4 tumor growths in the corresponding syngeneic hosts (BALB/c mice and C57BL/6 mice, respectively) without decreasing body weight and blood leukocyte count. UK-21 and UK-25 suppressed the proliferation of KB tumor cells in vitro (IC50: 3.0 x 10(-11) M and 4.4 x 10(-7) M, respectively) at concentrations almost equivalent to those of 5-FUR and 5-FU, respectively. These results suggest that UK-21 and UK-25 express their antitumor activity as 5-FUR and 5-FU, respectively. Neither UK-21 nor UK-25 suppressed thymus weight and humoral antibody production against sheep red blood cells (SRBC) in ddY mice, although 1-(2-tetrahydrofuryl)-5-fluorouracil (FT-207) and 5-FU suppressed them in their respective therapeutic dose ranges for tumors. Thus, UK-21 and UK-25 are expected to develop into anticancer drugs with lower immunotoxicological effects. PMID- 1513077 TI - Comparison of eicosanoids production between rat polymorphonuclear leukocytes and macrophages: detection by high-performance liquid chromatography with precolumn fluorescence labeling. AB - We developed a procedure for serial measurement of fluorescent derivatives of eicosanoids in biological samples by HPLC. The 9-anthryldiazomethane (ADAM) derivatized sample was first fractionated through SEP-PAK silica into fraction 1 (eluate of chloroform:toluene) and fraction 2 (eluate of acetonitrile:methanol). Both fractions were loaded separately onto an ODS column, and eluted with a step gradient of 85% and 95% acetonitrile for Fr-1 (HETE's and arachidonic acid) and with 70% acetonitrile for Fr-2 (PG's and LTB4). The method was applied to the arachidonate products of rat peritoneal leukocytes which were stimulated with A23187. The polymorphonuclear leukocytes (PMNL), which were collected after stimulation with casein, released mainly LTB4, 5-HETE, 6-K-PGF1 alpha, but little arachidonic acid. In contrast to PMNL, rat macrophages, which were collected after peritoneal injection of soluble starch and bacto peptone, released 5-HETE, arachidonic acid, and 6-K-PGF1 alpha, but no LTB4. These differences might be partly caused by the differential rates of uptake or turnover of arachidonic acid into their membrane phospholipids. PMID- 1513078 TI - Thrombolytic effects of a novel modified tissue plasminogen activator, E6010, on coronary thrombosis in the pig. AB - This study was conducted to compare the thrombolytic effect of a novel modified tissue plasminogen activator, E6010, with that of recombinant human tissue plasminogen activator (t-PA), administered by single intravenous bolus injection in pigs with occlusive coronary thrombosis. Thrombosis was induced by electrical stimulation of the intimal surface of the left circumflex coronary artery. Coronary blood flow velocity and hemodynamic parameters were observed for 1 hr after complete cessation of coronary flow. Ten minutes after heparin injection (300 U/kg), E6010, t-PA or placebo was intravenously administered as a bolus. E6010 at 0.2 and 0.4 mg/kg caused recanalization of the occluded coronary artery in 1 of 6 and 5 of 5 pigs, respectively. The time to recanalization after 0.4 mg/kg of E6010 was 22 +/- 11 min (mean +/- S.E.M.). t-PA (0.4 mg/kg) caused recanalization in only 1 of 5 pigs. Recanalization did not occur in any of the 6 animals administered placebo. Plasma clearance of E6010 was smaller than that of t-PA (4.9 +/- 0.3 vs. 9.4 +/- 3.8 ml/min/kg). There were no significant differences in plasma levels of fibrinogen, alpha 2-plasmin inhibitor and plasminogen among the placebo, E6010 and t-PA groups. These results suggest that the slower clearance of E6010 from plasma contributes to the effective thrombolytic action of E6010 following single intravenous bolus injection. PMID- 1513079 TI - Cisplatin-induced emesis in Suncus murinus. AB - Emetic responses to cisplatin and participation of vagal innervation in emesis were studied in suncus. Intraperitoneal and intravenous administration of cisplatin caused dose-dependent emesis. ED50 values, latencies and frequencies were not significantly different between the two administrations. Cis diaqodiammineplatinum (DAP), an active metabolite of cisplatin, also induced emesis, but with significantly shorter latency. Vagotomy completely abolished both types of vomiting. These results suggest that cisplatin is metabolized to DAP that subsequently causes emesis through stimulation of the vagus afferent. PMID- 1513080 TI - Kansas Medical Society Membership Directory 1992. PMID- 1513082 TI - Nutritional status and muscle amino acids in children with end-stage renal failure. AB - Nutritional status, assessed by anthropometric and biochemical methods, and muscle water, protein and amino acid composition, were evaluated in a control group of 10 children with normal renal function who were undergoing elective surgery, and in 15 children with end-stage chronic renal failure. Samples of the rectus abdominis muscle were taken when surgery was performed in the control children and when a peritoneal catheter was implanted in the uremic children. Height and body weight were reduced in the uremic children compared to the controls but skinfold thickness, arm muscle circumference and serum proteins (total protein, albumin, transferrin, pseudocholinesterase) were essentially normal. The muscle contents of total, extracellular and intracellular water, and of alkali-soluble protein (ASP), DNA and the ASP-DNA ratio were not significantly different in uremic children from those in the controls. Plasma leucine, isoleucine, tyrosine, valine, and serine levels were significantly decreased, whereas plasma citrulline, 1-methylhistidine and 3-methylhistidine levels were increased. Muscle isoleucine and valine levels and the valine/glycine ratio were low in the uremic children. Our results demonstrate that children with chronic renal failure and growth retardation may maintain a satisfactory nutritional status but exhibit amino acid abnormalities typical of uremia. PMID- 1513081 TI - Reduced activity of antioxidant enzymes underlies contrast media-induced renal injury in volume depletion. AB - Oxidant-mediated renal injury has been suggested as an important mechanism of acute renal failure induced by contrast media. Since volume depletion has been recognized as a predisposing factor for contrast media nephropathy, the present study was designed to characterize host-defense mechanisms against oxidant mediated renal injury during volume depletion. Antioxidant enzyme activities in renal cortex were compared between acutely water deprived (WD, 72 hours) and non WD rats. WD rats had reduced activities of catalase and superoxide dismutase activities (on average, 48% and 60% of values in non-WD, respectively). In separate groups of WD rats, saline or one of three different contrast media, namely diatrizoate meglumine/diatrizoate sodium (DTZ), ioxaglate meglumine/ioxaglate sodium (IXG), and iohexol (IHX) was injected. Both GFR and renal plasma flow rate, measured 24 hours later, was some 50% less in DTZ injected than saline-injected WD rats. WD rats treated with IXG and IHX had similar GFR to saline-treated rats. In DTZ-treated WD rats, specific products of membrane lipid peroxidation, phosphatidylcholine and phosphatidylethanolamine hydroperoxide, determined by chemiluminescent HPLC, were more than two-fold higher than saline, IXG, or IHX-treated WD rats. DTZ did not induce renal dysfunction and enhance lipid peroxidation in non-WD rats. Therefore, DTZ appeared to induce oxidant-mediated injury only in WD rats. When WD rats were pretreated with polyethylene glycol-coupled catalase (1.4 mg x 2 days), renal cortical catalase activity remained at a level similar to that of non-WD rats.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1513083 TI - Hemodialysis prescription and delivery in a metropolitan community. The St. Louis Nephrology Study Group. AB - The National Cooperative Dialysis Study attempted to determine adequacy of hemodialysis based on kinetic modeling of urea. Based on this study, it has been recommended that a dimensionless term quantitating the amount of dialysis delivered (KT/V) be greater than 1.0 to avoid adverse outcomes. With the declining duration of dialysis treatments in the United States, there has been concern that a significant proportion of patients may be receiving inadequate therapy. The purpose of this study was to survey hemodialysis practices and treatment outcomes in our metropolitan area. Sixteen area nephrologists volunteered to study their outpatient hemodialysis patients (N = 617). Demographic data and urea kinetic modeling results were then analyzed at the lead center. The mean length of dialysis was 3.2 +/- 0.4 (SD) hours with dialysis blood flow rates of 333 +/- 74 ml/min. The mean KT/V was 1.03 +/- 0.25 with nearly half of patients failing to attain a KT/V of 1.0. In 55% of patients the reason for a low KT/V was the prescription of an insufficient amount of dialysis treatment. In the remainder, insufficient delivery of prescribed dialysis contributed to the low KT/V. Only 1 of 33 patients undergoing dialysis twice a week achieved the recommended quantity of treatment on a weekly basis. Patients undergoing dialysis in non-profit units had a higher KT/V than those treated in proprietary units (1.1 +/- 0.26 vs. 0.92 +/- 0.22, P less than 0.001). In addition, patients dialyzed in units that performed urea kinetic modeling on all or selected patients had a higher KT/V compared to those in units where urea kinetics were not done (1.12 +/- 0.25 vs. 0.95 +/- 0.23, P less than 0.001). If these findings reflect practices elsewhere in the United States, many hemodialysis patients fail to receive the current recommended quantity of treatment. PMID- 1513084 TI - Simultaneous analysis of morbidity and mortality factors in chronic hemodialysis patients. AB - The Cox stepwise logistic regression model was applied to analyze 22 factors potentially affecting morbidity and mortality (MM) in a cohort of 104 patients on chronic hemodialysis (CHD). Two groups of predictor variables were considered: patients' characteristics at the start of the study, and treatment-related factors recorded throughout the observation period. End points were either failure (death or admission to a hospital) or success. Patients were followed for 24 months. Thirty-nine patients were hospitalized and seven died in the interval. The two leading causes of failure were cardiovascular and infectious complications. Variables significantly associated with the result were: cardiac status (score greater than 2, beta = 1.16), mean predialysis blood pressure (greater than 115 mm Hg, beta = 0.94), total dialysis dose (greater than 0.90, beta = -0.59) and age (greater than 55 years, beta = 0.51). The probability of failure was 0.13 for patients who presented the four variables in the lowest risk class. This increased to a maximum of 0.60 with one risk factor, to 0.91 with two risk factors, and to 0.99 with three or more risk factors. We conclude that, given the conditions for this study, two treatment-related variables of CHD (mean predialysis blood pressure and total dialysis dose) are MM factors even when simultaneously analyzed with other well-established predictors (cardiac status and age). Mean arterial pressure (MAP) is the most important CHD treatment related MM predictor. PMID- 1513085 TI - Comparison of hemodialysis and hemodiafiltration: a long-term longitudinal study. AB - Although hemodiafiltration is purported to provide better cardiovascular stability for dialysis patients; other possible benefits of this therapy have not been well defined. We have compared treatment with hemodialysis (HD) and hemodiafiltration (HDF) in 20 stable patients over a period of 18 months. Dialysis parameters (dialysate composition and flow, duration, dialyzer) were the same in the two periods except for the added convection of HDF and a higher tolerated blood flow in HDF. Cardiovascular parameters were remarkably similar in the two treatment periods, indicating that stable patients do not benefit further from this therapy in terms of these factors. The clearance of urea was significantly improved with HDF, which was reflected in a higher Kt/V and lower TACurea. We observed a significant correlation between Kt/V and PRU in both HD and HDF modes. This correlation was linear and the regression line was similar in both modes. The clearance of beta 2-microglobulin was also significantly improved by HDF compared to HD. Thus the benefit of HDF in stable dialysis patients is the improved clearance of small molecules and beta 2-microglobulin without increasing dialysis time. Further clinical benefits due to the improved clearance may only become apparent with longer follow-up. PMID- 1513086 TI - Intravenous 1,25 dihydroxycholecalciferol corrects glucose intolerance in hemodialysis patients. AB - The effects of intravenous 1,25 dihydroxycholecalciferol [(OH)2D3] on glucose tolerance and insulin secretion were studied in eleven uremic patients on regular hemodialysis and compared with eleven healthy controls. Intravenous glucose tolerance tests (IVGTT) were used to assess glucose tolerance, and the hyperglycemic clamp technique was used to quantitate endogenous insulin secretion. Three days after they had discontinued oral 1,25(OH)2D3, the dialysis patients were then studied with (+D) and without (-D) a single intravenous dose of 1,25(OH)2D3 at 2 micrograms/m2, given two hours before the IVGTT or clamp studies. During the -D studies, the uremic patients were glucose intolerant but not hyperinsulinemic. Intravenous 1,25(OH)2D3 in dialysis patients increased glucose uptake (K values) during IVGTT by 38% (P less than 0.02) and increased early component of insulin secretion during hyperglycemic clamps by 48% (P less than 0.01) and the late component by 32% (P less than 0.01). After intravenous 1,25(OH)2D3, the dialysis patients became hyperinsulinemic and regained glucose tolerance. Intravenous 1,25(OH)2D3 did not change the K values during IVGTT nor the insulin secretion during hyperglycemic clamps in the control subjects. During the -D studies, serum concentrations of 1,25(OH)2D3 were significantly lower in uremic patients compared with controls. Serum 1,25(OH)2D3 during the +D studies increased to supraphysiological levels in both uremic patients and controls. Serum concentrations of intact parathyroid hormone, total and ionized calcium, magnesium, potassium, urea nitrogen and creatinine were not different between the +D and -D studies in neither the uremic patients nor the controls. These results suggest that 1,25(OH)2D3 deficiency, independent of parathyroid hormone and calcium, may contribute to the abnormalities in glucose tolerance and insulin secretion in dialysis patients. PMID- 1513087 TI - Ventilatory and metabolic changes during high efficiency hemodialysis. AB - Ventilatory and metabolic changes were measured in seven patients undergoing high efficiency hemodialysis using a cuprophane dialyzer and bicarbonate-containing dialysate. At an HCO3 concentration of 35 mEq/liter and a mean in vivo urea clearance of 3.6 ml/kg/min, hypoxemia was not detected during dialysis (PaO2 was 14.00 and 13.60 kPa before and during dialysis). The new findings, related to high efficiency bicarbonate dialysis, include a sustained rise in minute ventilation (VE, 6.1 to 6.8 liter/min, P less than 0.01), an increase in CO2 excretion (VCO2, 194 to 214 ml/min, P less than 0.05), and O2 consumption (VO2, 215 to 246 ml/min, P less than 0.05). The increment in VE and VCO2 was attributed to the high flux rate of bicarbonate while the rise in VO2 is likely the result of metabolic alkalosis. Arterial pH rose from 7.40 to 7.49 mm Hg and serum HCO3 increased from 23.8 to 29.2 mEq/liter, while pCO2 remained normal at 5.07 kPa throughout the study. The acid-base status of the blood changed from that of a metabolic acidosis to that of a respiratory acidosis across the dialyzer where the pH decreased from 7.47 to 7.41 and pCO2 rose from 5.31 to 7.72 kPa. These data indicate that a healthy ventilatory response is needed to excrete the excess CO2 generated during high efficiency bicarbonate hemodialysis. The significance and etiology of the elevated O2 consumption is undetermined. PMID- 1513088 TI - Heparan sulfate proteoglycan in the glomerular basement membrane in type 1 diabetes mellitus. AB - Heparan sulfate proteoglycans (HSPG) are negatively charged constituents of the renal extracellular matrix including the glomerular basement membrane (GBM) and mesangial matrix. Biochemical and functional studies of patients with type-1 insulin dependent diabetes mellitus (IDDM) suggest that alterations of HSPG may occur in diabetic nephropathy. We have utilized a specific cytochemical method and electron microscopy to quantitate the distribution of HSPG in the GBM of 10 normal people and in 16 IDDM patients with a spectrum of clinical and structural changes. Enzyme incubation studies of normal infant kidney demonstrated that heparitinase removed 94% of the stainable anionic sites in the lamina rara externa (LRE) and 77% of the sites in the lamina rara interna (LRI) of the GBM. In contrast, incubation in the enzyme chondroitinase ABC did not reduce the number of sites in the LRE but reduced the number of sites in the LRI by 26%. The HSPG anionic sites in normal subjects were distributed in the LRE as 20.9 +/- 1.3, and in the LRI as 13.1 +/- 2.2 per micron GBM length. Anionic sites were slightly reduced (19.6 +/- 1.3, P less than 0.04) in the LRE of IDDM patients with normal urinary albumin excretion rates (UAE), or microalbuminuria, and were reduced in both the LRE and LRI of IDDM patients with clinical proteinuria (13.1 +/- 2.3, P less than 0.001 and 8.9 +/- 2.1, P less than 0.001, respectively). The number of anionic sites in the LRE and LRI, respectively, correlated with UAE (r = +0.78, P less than 0.001, r = +0.58, P less than 0.02), with GBM thickness (LRE, r = +0.81, P less than 0.001; LRI, r = +0.67, P less than 0.01) and with the volume fraction of mesangium (LRE, r = +0.59, P less than 0.02; LRI, r = +0.58, P less than 0.03). These data confirm earlier biochemical findings of a reduction of HSPG in the GBM in advanced diabetic nephropathy but do not provide evidence for the loss of HSPG in the GBM as a mechanism for early microalbuminuria. PMID- 1513089 TI - Measurement of GFR with a single intravenous injection of nonradioactive iothalamate. PMID- 1513090 TI - Estimation of glomerular volume: a comparison of four methods. AB - Methods for estimating glomerular volume were compared in Zenker-fixed, paraffin embedded biopsies from 10 patients with insulin-dependent diabetes mellitus and 6 normal kidney donors. Two methods of measurement of individual glomerular volumes were used: the Cavalieri method (considered the "gold standard") and the maximal profile area (MPA) method. Also studied were the method of Weibel and Gomez and a method based on the disector principle; both estimate mean volume (VG). MPA and Cavalieri showed strong correlation (r = 0.93; P less than 0.001), although the MPA method consistently overestimated the true volume; six glomeruli were necessary for a reliable estimate of VG. The disector method did not correlate with VG determined by Cavalieri. Weibel-Gomez did correlate with Cavalieri (r = 0.68; P less than 0.05), but overestimated VG. At least 15 profiles were needed to provide a dependable estimate of VG by Weibel-Gomez. The Cavalieri, MPA, and Weibel-Gomez methods all can provide reliable estimates of VG, the latter two with appropriate correction factors. The individual glomerular volume methods, while more time consuming, provide information on variation and distribution of the glomerular population and are the methods of choice for studies of glomerular volume. PMID- 1513091 TI - Molecular pathogenesis of membranous nephropathy. PMID- 1513092 TI - Is diabetic nephropathy an inherited complication? AB - For yet unidentified reasons less than 50% of patients with insulin-dependent mellitus develop diabetic nephropathy. Genetic factors have been suggested as risk markers for development of nephropathy in diabetes. To further evaluate this hypothesis we studied the prevalence of nephropathy in diabetic siblings of diabetic patients with and without nephropathy. From a representative sample of 619 patients with insulin-dependent diabetes, we identified 20 patients with and 29 patients without nephropathy having diabetic siblings. Diabetic nephropathy (defined as urinary albumin excretion greater than 300 mg/24 hr) was found in 7 out of 21 siblings to patients with nephropathy and 3 out of 30 siblings to normoalbuminuric patients (P less than 0.04). No significant differences between the two groups of siblings with respect to age, diabetes duration, sex distribution, blood pressure or glycosylated hemoglobin A1c-levels were found. A significant correlation within sib-pair of glycosylated hemoglobin A1c was found (r = 0.47; P less than 0.001). We conclude that familial clustering of diabetic nephropathy does occur. This clustering may either be due to genetic inheritance or to sib-similarities due to shared environment, as indicated by the correlation of glycosylated hemoglobin A1c within sib-pairs. PMID- 1513093 TI - Predisposition to hypertension: risk factor for nephropathy and hypertension in IDDM. AB - Less than a quarter of the patients with juvenile-onset IDDM develop diabetic nephropathy during the first 20 years of diabetes. To study the determinants of this complication, we selected patients who had come with newly diagnosed IDDM to the Joslin Clinic between 1967 to 1972, and we examined them in 1986 to 1988, that is, 15 to 21 years after onset of diabetes. Using a case control design we compared three groups of cases, that is, advanced nephropathy (N = 43), only microalbuminuria (N = 41), and hypertension alone (N = 17), with a group of controls who remained normoalbuminuric and normotensive despite the long duration of IDDM (N = 61). In comparison with controls, patients with advanced nephropathy had more parents with hypertension (odds ratio 3.8), higher Vmax values of Na/Li countertransport in red blood cells (odds ratio 10.0 for the highest tertile), and higher mean arterial pressure during adolescence and early adulthood (odds ratio 3.1 for those above the median). They also had significantly poorer glycemic control during their first 12 years of diabetes. Patients with hypertension alone were similar to those with advanced nephropathy with regard to markers of predisposition to hypertension but differed from them with regard to glycemic control, having the best glycemic control of all the study groups. Patients who developed only microalbuminuria during 15 to 21 years of IDDM (some of whom will progress to overt proteinuria later) did not differ significantly from controls with regard to predisposition to hypertension. In conclusion, predisposition to hypertension is a major risk factor for the development of advanced diabetic nephropathy and essential hypertension during the first 20 years of IDDM. PMID- 1513094 TI - Eight to nine year mortality in known non-insulin dependent diabetics and controls. AB - Microalbuminuria is known to predict mortality in elderly, non-insulin dependent diabetic individuals. To test whether this is also so when studied prospectively and over a longer period, we followed 228 persons with known diabetes mellitus and an age and sex matched, non-diabetic cohort for eight to nine years. Both cohorts were found during a population screening in 1981-1982 of 5292 citizens aged 60 to 74 years. At ascertainment extensive clinical and biochemical examinations including determination of urinary albumin were carried out. At May 15, 1990 111 diabetic and 46 non-diabetics had died (P less than 0.0001). In the diabetic cohort the median value of urinary albumin excretion (UAE) was 17.40 micrograms/min. In the group with values at or above 17.40 micrograms/min 62 died, compared with 40 deaths in the group with values below (P = 0.003). In the non-diabetic cohort the median UAE value was 7.52 micrograms/min. In the upper group 26 died, in the lower 15 (P = 0.05). Cox regression analyses showed coefficients of regression for ln(UAE) of 0.333 (P less than 0.001) for the diabetic group and 0.236 (P = 0.048) for the non-diabetic group. In the Cox model for the diabetics, ischemic heart disease was also of independent significance to mortality. The final model for the non-diabetics included hypertension and sex as significant variables. It is concluded that in a prospective study of elderly diabetics urinary albumin excretion rate is the best prognostic factor for long term mortality.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1513095 TI - Relationship of systemic blood pressure to nephropathology in insulin-dependent diabetes mellitus. AB - Although hypertension is an important complication of diabetes it is unclear whether its association with other diabetic complications represents cause or consequence. Our study is a cross sectional evaluation of the relationship of blood pressure to renal structural and functional parameters. In 139 patients with insulin dependent diabetes for 18.9 +/- 7.4 years (mean +/- SD), we divided the patients into those with markedly increased mesangial volume fraction [Vv(mes/glom) greater than or equal to 0.37] and those with less [Vv(mes/glom) less than 0.37]. Hypertension (systolic BP greater than or equal to 160 and/or diastolic BP greater than 90 mm Hg or receiving BP medications) occurred in 29/40 with Vv(mes/glom) greater than or equal to 0.37. All 40 had clinical nephropathy with urinary albumin excretion (UAE) greater than 200 mg/24 hr. By two-way ANOVA creatinine clearance was lower and albuminuria was increased with both hypertension and the expanded mesangium. Also other measures of renal structure including filtration surface, index of interstitial fibrosis and index of arteriolar hyalinosis were increased by hypertension and mesangial expansion. Most patients with hypertension had other criteria for clinical nephropathy. Since, in these studies, we could not determine if hypertension contributed to or resulted from the renal lesions, we developed an estimate of the rate of mesangial expansion. We found that patients with normal BP (119 +/- 11/78 +/- 7 mm Hg) can be rapidly developing mesangial expansion. These studies support the view that the development of serious renal lesions can be independent of hypertension in IDDM.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1513096 TI - Glomerular structure in type-1 (insulin-dependent) diabetic patients with normo- and microalbuminuria. AB - Kidney biopsies from 15 type-1 (insulin-dependent) diabetic patients with a range of albumin excretion (AER) were analyzed. Nine patients had normal AER, and six had microalbuminuria. Basement membrane thickness, BMT, and mesangial matrix volume fraction, Vv(mat/glom), were obtained from at least three glomeruli per biopsy. Mesangial structures were estimated with electron microscopic analysis at three levels in each glomerulus. Glomerulopathy parameters were significantly increased in micro- versus normoalbuminuric patients with the following means and (CV): BMT 571 nm (0.12) and 442 nm (0.25), P = 0.03; Vv(mes/glom) 0.31 (0.20) and 0.22 (0.14), P = 0.002; Vv(matrix/glom) 0.17 (0.25) and 0.11 (0.28), P = 0.006; matrix star volume 56 microns 3 (0.47) and 22 microns 3 (0.43), P = 0.02. A positive correlation obtained between AER and each of the glomerulopathy parameters, BM thickness, Vv(mes/glom) and Vv(matrix/glom), as well as between AER and a structural index expressing the sum of changes in the peripheral BM and in the mesangium (r = 0.62, P = 0.01). The results indicated a parallel course of mesangial and peripheral BM changes: a positive correlation obtained between BM thickness and mesangial parameters [BMT versus Vv(matrix/glom): r = 0.82, P = 0.0001] and the ratio of the two subsets of glomerular BM material (PBM:matrix) did not show significant difference between normo- and microalbuminuric groups. The data give strong support to the contention that the transition from normo- into the microalbuminuric phase is linked to progressing glomerulopathy. PMID- 1513097 TI - An electron microscopic study of glomeruli in Japanese patients with non-insulin dependent diabetes mellitus. AB - Renal biopsy specimens of 29 Japanese non-insulin dependent diabetes mellitus (NIDDM) patients were examined by quantitative electron microscopic morphometry. In NIDDM the relative increase of percent total mesangium and mesangial capillary surface density (S/Vb) and the relative decrease of peripheral capillary surface density (S/Va) were compared with disease controls. However, mesangial-GBM epithelial surface density (S/Vc) was not different between both groups. These results suggest that the increased mesangial matrix expands directly towards the capillary lumen as well as along the inner surface of GBM, and narrows the capillary lumen and filtration surface. The duration of diabetes mellitus (DM) did not correlate with all morphological parameters. The mesangial expansion correlated with urinary protein excretion and decreased creatinine clearance (CCr). GBM thickening correlated with proteinuria, but not with CCr. The degree of these morphological changes could be the indicators of hypertension of NIDDM patients. Areas of thin GBM were occasionally noticed in glomeruli which revealed thick GBM extensively, although the mechanism of GBM thinning is not known at the present time. PMID- 1513098 TI - Prevalence and causes of albuminuria in non-insulin-dependent diabetic patients. AB - A prospective study of the prevalence and causes of persistent albuminuria (greater than 300 mg/24 hr) was conducted in non-insulin-dependent diabetic (NIDDM) patients, age less than 66 years, attending a diabetic clinic during 1987. All eligible patients (N = 370) were asked to collect at least one 24-hour urine sample for albumin analysis. Urine collection was obtained in 224 males and 139 females (98%). Fifty patients (7 women) suffered from persistent albuminuria (13.8%). The prevalence of albuminuria was significantly higher in males (19%) than in females (5%). A kidney biopsy was performed in 35 patients (70%). The kidney biopsies revealed diffuse and/or nodular diabetic glomerulosclerosis in 27 patients (77%), while the remaining eight patients (23%) had a variety of non diabetic glomerulopathies, such as minimal lesion and mesangioproliferative glomerulonephritis. Diabetic retinopathy was present in 15 of 27 patients (56%) with diabetic glomerulosclerosis, while none of the eight patients with a non diabetic glomerulopathy had retinopathy. Our cross sectional study has revealed a high prevalence of albuminuria and of non-diabetic glomerulopathy as a cause of this complication in NIDDM patients. Presence of diabetic retinopathy strongly suggests that a diabetic glomerulopathy is the cause of albuminuria. Albuminuric non-insulin-dependent diabetic patients without retinopathy require further evaluation, that is, kidney biopsy. PMID- 1513099 TI - Inhibition of glomerular glucosaminyl N-deacetylase in diabetic rats. AB - The enzyme glucosaminyl N-deacetylase plays a key role in heparan sulphate biosynthesis since N-deacetylation is a prerequisite for N- and further O sulphation of the carbohydrate polymer. Diabetes induced inhibition of this enzyme could be an important factor in the development of diabetic nephropathy. In this study glomerular glucosaminyl N-deacetylase activity and urinary albumin excretion were measured in insulin-treated streptozotocin-diabetic rats. Furthermore, in an attempt to provide evidence of genetically dependent differences in the vulnerability of the N-deacetylase enzyme, two closely related rat strains (H and U) were studied. A significant 10% inhibition in enzyme activity was found among rats with mean blood glucose values between 9 and 17 mmol/liter, P less than 0.05. There was a pronounced difference between the two rat strains in the vulnerability of the enzyme against blood glucose alterations. The U rat appeared highly sensitive to short-term blood glucose control judged by the correlation between blood glucose and N-deacetylase activity (r = -0.73, P = 0.005, N = 16), where no such correlation was found in the H rat (r = 0.02, P = 0.9, N = 14). Urinary albumin excretion was increased in diabetic H rats and significantly correlated to glomerular N-deacetylase activity (r = -0.62, P = 0.02, N = 14). The U rats developed a 10-fold rise in albumin excretion compared to H rats, but this albuminuria was apparently not related to the presence of diabetes or correlated to glomerular N-deacetylase activity. It is concluded that the diabetes induced inhibition of glucosaminyl N-deacetylase may play an important role in the pathogenesis of diabetic nephropathy. PMID- 1513100 TI - Diabetes-induced glomerular dysfunction: links to a more reduced cytosolic ratio of NADH/NAD+. AB - These studies were undertaken to examine effects of elevated glucose levels on glycolysis, sorbitol pathway activity, and the cytosolic redox state of NADH/NAD+ in isolated glomeruli. Blood-free glomeruli were isolated from kidneys of male, Sprague-Dawley rats using standard sieving techniques, then incubated for one hour at 37 degrees C, pH 7.4, pO2 approximately 500 torr, in Krebs bicarbonate/Hepes buffer containing 5 or 30 mM glucose. Elevated glucose levels increased glucose 6-phosphate, fructose 6-phosphate, total triose phosphates, lactate, the lactate/pyruvate ratio, sorbitol, and fructose, but did not affect sn-glycerol 3-phosphate, pyruvate, or myo-inositol levels. The more reduced glomerular cytosolic redox state (manifested by the tissue lactate/pyruvate ratio) induced by 30 mM glucose was completely abrogated by aldose reductase inhibitors added to the diet two to seven days prior to glomerular isolation. These observations, coupled with evidence linking glucose- and diabetes-induced glomerular dysfunction to increased sorbitol pathway metabolism, support the hypothesis that metabolic imbalances associated with a more reduced ratio of cytosolic NADH/NAD+ (resulting from increased glucose metabolism via the sorbitol pathway) play an important role in mediating glucose- and diabetes-induced glomerular dysfunction. PMID- 1513101 TI - Effects of diabetes and insulin on expression of kallikrein and renin genes in the kidney. AB - We previously showed that renal prokallikrein synthesis is reduced in streptozotocin (STZ)-diabetic rats. Plasma renin activity is also reduced in diabetic rats. To investigate the molecular mechanisms underlying these changes, we examined the effects of diabetes and insulin treatment on renal kallikrein and renal renin mRNA levels and the activities of these enzymes. Rats made diabetic by STZ were either treated with 1.5 to 1.75 U PZI insulin daily to maintain moderate hyperglycemia (plasma glucose 200 to 300 mg/dl, D + I) or left untreated to produce severe hyperglycemia (plasma glucose greater than 400 mg/dl, D). Control (C) rats were also studied. After three weeks, renal kallikrein mRNA was reduced 50% in D rats. A proportional reduction in immunoreactive kallikrein was also observed (37.8 +/- 2.5 vs. 55.8 +/- 6.8 ng/mg protein, D vs. C, P less than 0.001). Kallikrein mRNA and immunoreactive kallikrein levels in D + I rats were not different from C rats. Renin mRNA level was also markedly reduced in D rats, compared to C rats. This was associated with reduced plasma renin concentration (4.5 +/- 0.2 vs. 10.5 +/- 1.6 ng Ang I/ml/hr, D vs. C, P less than 0.01). However, renal renin concentration was unchanged (0.84 +/- 0.17 vs. 0.84 +/- 1.3 micrograms Ang I/mg protein/hr, D vs. C). In D + I rats, renin mRNA level and plasma renin concentration were not different from C levels. However, renal renin concentration was increased (1.49 +/- 0.27 micrograms Ang I/mg protein/hr) compared to C rats (P less than 0.05). beta-actin mRNA levels were unchanged in either diabetic rat group.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1513102 TI - Renin and angiotensinogen gene expression in experimental diabetes mellitus. AB - The renin-angiotensin system may play a role in the initiation and progression of diabetic kidney disease. In this study, the local intrarenal renin-angiotensin system was examined in streptozotocin-treated rats maintained moderately hyperglycemic by daily low-dose insulin injection. Four weeks after induction of diabetes, plasma renin activity was significantly lower in the diabetic compared to a non-diabetic control group (diabetes: 2.30 +/- 0.30 vs. control: 6.93 +/- 1.36 ng Al/ml/hr; P less than 0.01). Renal tissue renin content (diabetes: 1.81 +/- 0.46 vs. control: 2.05 +/- 0.27 micrograms Al/mg protein/hr; P less than 0.05) and renal renin mRNA (diabetes: 2.32 +/- 0.16 vs. control: 1.89 +/- 0.12 pg/micrograms RNA; P = NS) were not different between diabetic and control rats. Renal and liver angiotensinogen mRNA were lower in the diabetic group. Glomerular renin mRNA was not different between the diabetic and sham group. The dissociation between systemic renin activity (a decrease), and in renal renin content or mRNA in the diabetic rats (no change), suggests a post-translational alteration in renin processing and/or renin secretion. PMID- 1513103 TI - Octreotide administration in diabetic rats: effects on renal hypertrophy and urinary albumin excretion. AB - Initial renal hypertrophy in experimental diabetes is prevented by administration of a long-acting somatostatin analogue octreotide (SMS). To investigate the long term effects of SMS on renal hypertrophy and urinary albumin excretion (UAE), streptozotocin-diabetic and non-diabetic rats were treated with two daily subcutaneous injections of SMS (100 micrograms x 2) for six months. Untreated diabetic and non-diabetic animals were used as reference groups. No differences were seen between the two diabetic groups in respect to body weight, food intake, blood glucose levels, urinary glucose output, hemoglobin A1C(HbA1C), fructosamine, serum growth hormone (rGH) or creatinine clearance, but kidney weight (896 +/- 36 vs. 1000 +/- 24 mg, P less than 0.02), UAE (417 +/- 131 vs. 1098 +/- 187 micrograms/24 hr, P less than 0.02), kidney insulin-like growth factor I (IGF-I) (167 +/- 16 vs. 239 +/- 17 ng/g, P less than 0.01) and serum IGF I (301 +/- 26 vs. 407 +/- 17 micrograms/liter, P less than 0.01) were all reduced in the SMS-treated diabetic animals when compared to the untreated diabetic group. In non-diabetic rats SMS reduced body weight (274 +/- 3 vs. 293 +/- 5 g, P less than 0.01), kidney weight (695 +/- 9 vs. 764 +/- 17 mg, P less than 0.01), UAE (83 +/- 29 vs. 364 +/- 114 micrograms/24 hr, P less than 0.02), kidney IGF-I (202 +/- 12 vs. 280 +/- 12 ng/g, P less than 0.01), serum IGF-I (428 +/- 21 vs. 601 +/- 54 micrograms/liter, P less than 0.01) and serum rGH (67 +/- 6 vs. 126 +/ 27 micrograms/liter, P less than 0.05) when compared to untreated controls. When kidney weights were expressed in relation to body weight no difference was found between SMS-treated and untreated controls, while the difference between SMS treated and untreated diabetic animals was still present (P less than 0.01). In conclusion, chronic administration of SMS has abating effects on diabetic renal hypertrophy and UAE, and thus indicates that SMS may reduce development of diabetic kidney lesions in experimental diabetes. The long-term suppressive effects of SMS on renal enlargement and UAE may in part be mediated through reduction in circulating and kidney IGF-I levels. PMID- 1513104 TI - Increased glomerular filtration rate as a predictor of diabetic nephropathy--an 8 year prospective study. AB - The objective was to study the natural history and the predictive value of glomerular filtration rate, albumin excretion rate, blood pressure, and hemoglobin A1c for diabetic nephropathy. A cohort of 75 type-1 diabetic adolescents with a diabetes duration of 8 years was studied. Thirty-one females, 33 males, mean age 16.9 +/- 0.3 (SEM) participated in the follow-up study. Glomerular filtration rate, albumin excretion rate, blood pressure, and hemoglobin A1c were measured every second year during 8 years to determine the predictive value of glomerular filtration rate for future nephropathy. Initial differences and patterns of changes in glomerular filtration rate, albumin excretion rate, and hemoglobin A1c were examined in patients who did (group 1) and did not (group 2) develop incipient or overt nephropathy. Five of 64 patients developed overt nephropathy. They had an initial glomerular filtration rate of greater than 125 ml/min/1.73 m2. Fifteen of 53 initially normoalbuminuric patients developed incipient and three of 53 overt nephropathy. Age, age at onset, diabetes duration, initial albumin excretion rate, initial blood pressure, and hemoglobin A1c were similar in groups 1 and 2. Glomerular filtration rate was initially higher in group 1 than in group 2 (P = 0.01). The positive predictive value for combined incipient and overt nephropathy of an initial glomerular filtration rate greater than 125 ml/min was 53%. The negative predictive value of glomerular filtration rate less than 125 ml/min was 95%. In initially normoalbuminuric patients multiple regression revealed initial glomerular filtration rate as the only significant independent predictor for nephropathy when also corrected for hemoglobin A1c (P = 0.04).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1513105 TI - Renal hemodynamics in newly presenting non-insulin dependent diabetes mellitus. AB - Little information is available regarding renal hemodynamics in non-insulin dependent diabetics (NIDDMs), despite their numerical significance to renal support programs. Therefore, simultaneous determination of glomerular filtration rate (GFR) and effective renal plasma flow (ERPF) (expressed to 1.73 m2 surface area) was performed in 110 newly presenting normotensive NIDDMs [mean (SD) age: 52.5 (10.1) years] and compared with 32 normal subjects of similar age range [age: 52.2 (11.3) years]. Mean (SD) GFR, ERPF and filtration fraction (FF) for the NIDDMs were: 117 (22) ml/min (range: 74 to 178), 534 (123) ml/min and 22.4 (3.0)%, and for the normals: 95 (12) ml/min (range: 75 to 119), 472 (70) ml/min and 20.2 (2.2%), respectively. As a group, NIDDMs demonstrated significantly greater GFR (P less than 0.001), ERPF (P less than 0.005) and FF (P less than 0.001). GFR values above 140 ml/min were observed in 16% of the NIDDMs, while 45% had GFRs in excess of mean +/- 2 SD of the normals. NIDDMs demonstrated a positive relationship for GFR with ERPF (P less than 0.001) and an inverse association for both GFR and ERPF with age (P less than 0.001). Multivariable regression analysis revealed ERPF as the strongest explanatory variable for GFR in the NIDDMs (P less than 0.001), followed by age (P less than 0.01). Significant contributions to the regression analysis were not observed for body mass index, systolic or diastolic blood pressures, glycosylated hemoglobin nor fasting levels of plasma glucose, cholesterol, HDL-cholesterol, LDL-cholesterol and triglycerides. Urinary albumin excretion rates were not correlated with GFR, ERPF or FF. Microalbuminuria was detected in 7% of the NIDDMs in this study.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1513106 TI - Prognostic significance of microalbuminuria in insulin-dependent diabetes mellitus: a twenty-three year follow-up study. AB - A cohort of 63 Type 1 insulin-dependent diabetic patients were first characterized for overnight urinary albumin excretion rate (AER) in 1967. In 1981, seven out of eight (87%) patients with initial AER greater than or equal to 30 less than or equal to 140 micrograms/min (microalbuminuria) developed clinical proteinuria compared to only 2 out of 55 (4%) patients with initial AER less than 30 micrograms/min. The same cohort of patients was reassessed in 1990 after a total follow-up period of 23 years. The aim was to investigate the role of microalbuminuria in the prediction of total/cardiovascular mortality and the development of renal failure, in addition to clinical proteinuria. The initially microalbuminuric patients had a significantly higher risk of developing not only clinical proteinuria (relative risk 9.3, 95% C.I. 1.36 to 3.10, P less than 0.05), but also of dying from a cardiovascular cause (relative risk 2.94, 95% C.I. 1.18 to 7.34, P less than 0.05). The rate of progression to renal failure was higher but not significantly so in the microalbuminuric (2 of 8) compared to the normoalbuminuric (4 of 53) group (relative risk 3.31, 95% C.I. 0.72 to 15.24, NS). In insulin-dependent diabetic patients microalbuminuria is a powerful predictor of clinically overt diabetic renal disease as well as cardiovascular mortality. PMID- 1513107 TI - Ambulatory blood pressure in microalbuminuric type 1 diabetic patients. AB - Twenty-four-hour ambulatory blood pressure (AMBP) was performed in microalbuminuric (micro.) type 1 diabetic patients, with the aim of comparison with a matched group of normoalbuminuric patients (normo.) and healthy controls. Thirty-four patients without antihypertensive medication were investigated in each group. Urinary albumin excretion (UAE) for micro. was (geometric mean, tolerance factor microgram/min) 51.7 x/divided by 1.94, 5.1 x/divided by 1.88 for normo. and 5.2 x/divided by 1.75 for controls. Twenty-four-hour AMBP (mean systolic/diastolic mm Hg +/- SD) was significantly higher in micro. (131 +/- 10/78 +/- 7) than in normo. (122 +/- 8/73 +/- 6; P less than 0.001/P less than 0.01). No 24-hour AMBP difference between normo. and controls (120 +/- 9/71 +/- 7) was found. No difference in the night/day ratio of blood pressure was found between the diabetic groups. Coefficient of variation for day time systolic measurements did not show any intergroup difference. Systolic day time blood pressure for the pooled diabetic group correlated significantly with UAE (r = 0.45, P less than 0.001), whereas no significant correlation with auscultatory systolic values in the clinic was found (r = 0.21; P = 0.09). In conclusion, blood pressure in micro. as compared to normo. is not more labile but is elevated day and night without significant alteration of the diurnal rhythm. AMBP reflects the association between UAE and blood pressure more precisely than clinical measurements and may be preferable for identifying candidates for antihypertensive treatment. PMID- 1513108 TI - Clustering of risk factors in hypertensive insulin-dependent diabetics with high sodium-lithium countertransport. AB - Diabetic nephropathy is more common in patients with a positive family history of hypertension and with elevated red blood cell sodium-lithium countertransport, a marker of risk for essential hypertension. To evaluate whether there is a relationship between this cation transport system and indicators of risk of renal and cardiovascular complications in diabetic patients before the development of clinical proteinuria, we studied 31 type 1 (insulin-dependent) diabetic patients with arterial hypertension, without clinical proteinuria and 12 normotensive normoalbuminuric diabetic patients. Sodium-lithium countertransport activity was significantly higher in hypertensive patients (0.43 +/- 0.03 mmol/l RBC x hr) than in normotensive patients (0.23 +/- 0.03; P less than 0.001). To better explore the nature of the association between this transport system and arterial hypertension, hypertensive patients were divided in two groups, with high (greater than 0.41 mmol/l RBC x hr) or normal (less than 0.41) sodium-lithium countertransport activity. The two groups of hypertensive diabetics were similar in age, sex, body mass index and blood pressure levels.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1513109 TI - Is increased erythrocyte sodium-lithium countertransport a useful marker for diabetic nephropathy? AB - Genetic predisposition to essential hypertension has been proposed as a risk factor for the development of diabetic nephropathy in type 1 (insulin-dependent) diabetes mellitus. An increased sodium-lithium countertransport activity (NaLiCT) has been suggested as a genetic marker for essential hypertension. We therefore evaluated NaLiCT in diabetic patients with (N = 39) or without (N = 23) diabetic nephropathy (DNP), patients with non-diabetic renal diseases (N = 42) and in healthy controls (N = 24). The NaLiCT was elevated in both diabetic patient groups compared to healthy controls (median 244; range 134 to 390 mumol.liter cells-1.hr-1), but was not different in patients with DNP (median 314; range 162 to 676), without DNP (median 325; range 189 to 627) and patients with non diabetic renal disease (median 300; range 142 to 655). The genetic predisposition to DNP is illustrated by the fact that diabetic sibs of probands with DNP showed a higher occurrence of DNP than diabetic sibs of patients without DNP. We analyzed whether familial DNP clustered with an increased NaLiCT. The NaLiCT in sibs concordant for the presence of DNP (N = 10; median 307; range 217 to 428 mumol.liter cells-1.hr-1) was not significantly different from that in sibs concordant for absence of DNP (N = 15; median 279; range 189 to 442). We conclude that erythrocyte sodium-lithium countertransport activity cannot be used as a marker to identify patients at risk for the development of diabetic nephropathy. PMID- 1513110 TI - Prevalence of raised sodium-lithium countertransport activity in type 1 diabetic patients. AB - The prevalence of raised Na+/Li+ countertransport (CT) activity (greater than 0.41 mmol/liter RBC/hr) was assessed in 185 consecutive insulin-dependent diabetic patients attending an outpatient diabetic clinic. Normoalbuminuria was defined as an overnight albumin excretion rate (AER) of less than 20 micrograms/min (N = 121), microalbuminuria as AER between 20 and 150 micrograms/min (N = 35) and macroalbuminuria as AER greater than or equal to 150 micrograms/min (N = 29). The prevalence of elevated Na+/Li+CT (greater than 0.41 mmol/liter RBC/hr) was 21.5, 42.8 and 51.7% (P = 0.0005), in patients with normo , micro- and macroalbuminuria, respectively. In the whole group, Na+/Li+CT was significantly related to mean blood pressure (MBP; rs = 0.37, P less than 0.001) and AER (rs = 0.38, P less than 0.001). In a multiple regression analysis the significant correlates of AER, as a continuous variable, or of proteinuria (micro + macroalbuminuria), as a categorical variable, were Na+/Li+CT, MBP, duration of diabetes and glycosylated hemoglobin (HbA1). The frequency of normoalbuminuric patients with high Na+/Li+CT activity fell with duration of diabetes. The risk of proteinuria was significantly greater in patients with raised Na+/Li+CT compared to those with Na+/Li+CT within the normal range (odds ratio 3.8, 95% CI, 1.9 and 7.8). A relative excess of patients with proteinuria (micro + macroalbuminuria) was found in the group with elevated Na+/Li+CT and HbA1 above the median value (8.05%) of the whole population (chi 2 = 9.7, P less than 0.002).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1513111 TI - Antihypertensive therapy in a model combining spontaneous hypertension with diabetes. AB - We have compared the effects of the angiotensin converting enzyme inhibitor, perindopril, and a conventional antihypertensive regimen (triple therapy: hydralazine, reserpine and hydrochlorothiazide) on kidney function and albuminuria in hypertensive diabetic rats. Diabetes was induced with streptozotocin in spontaneously hypertensive (SHR) rats and they were randomized to receive no treatment, perindopril or triple therapy. Antihypertensive drugs were commenced at the time of induction of diabetes and continued for 16 weeks. Blood pressure reduction was equal in the groups treated with perindopril or triple therapy. All groups had similar severity of diabetes as determined by body weight, serum glucose and glycated hemoglobin levels. Whereas plasma renin activity rose in both the perindopril and triple therapy groups, it is likely that the effects on angiotensin II levels were opposite since perindopril but not triple therapy was associated with a significant reduction in plasma angiotensin converting enzyme activity. Diabetes was associated with an increase in glomerular filtration rate. At 12 weeks, glomerular filtration rate was higher in the perindopril treated group when compared to the triple therapy group, but neither group treated with antihypertensive therapy was different to untreated diabetic rats. Both drug regimens reduced albuminuria in the diabetic rats to a similar degree apparently independently of their effects on the renin-angiotensin system. Studies in diabetic subjects are warranted to evaluate different classes of antihypertensive drugs with respect to their effects on kidney function, proteinuria and glomerular morphology. PMID- 1513112 TI - Angiotensin converting enzyme inhibition and calcium channel blockade in incipient diabetic nephropathy. The Melbourne Diabetic Nephropathy Study Group. AB - Small increases in blood pressure are a feature of incipient diabetic nephropathy, and mean blood pressure often correlates with the degree of albuminuria in such patients. Antihypertensive therapy with angiotensin converting enzyme inhibitors (CEI) or calcium channel blockers (CCB) has been assessed in several studies to determine if either form of treatment modifies incipient diabetic nephropathy and its evolution to established nephropathy. The acute renal hemodynamic effects of CEI differ from those of CCB under certain circumstances. In incipient diabetic nephropathy, therapy with CEI but not CCB tends to reduce filtration fraction, especially in hyperfiltering patients. In hypertensive patients with incipient diabetic nephropathy, both treatments result in a decrease in albuminuria and the responses are mainly dependent on the lowering of systemic blood pressure. In normotensive patients with incipient diabetic nephropathy, a lowering of mean blood pressure with CEI or CCB is not found consistently while effects on albuminuria are difficult to interpret. Short and long-term therapy with CEI lowers or stabilizes albuminuria. Short-term administration of CCB has at times been associated with increases in albuminuria, but a comparison of CEI and CCB over 12 months in the Melbourne Diabetic Nephropathy Study (MDNS) has shown that both drugs stabilize albuminuria with no significant differences in their effects. Serial analysis of urinary sodium excretion in the MDNS shows that the hypotensive response to CEI in incipient nephropathy is highly dependent on sodium intake, and that sodium intake may modulate albuminuria during both CEI and CCB therapy.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1513113 TI - Long-term glycemic control and kidney function in insulin-dependent diabetes mellitus. AB - In this paper we examined the relationship between blood glucose control and initiation and progression of increased urinary albumin excretion. In this seven year Oslo study 45 insulin-dependent diabetes mellitus patients were initially randomized into three different modes of treatment: continuous subcutaneous insulin infusion (CSII), multiple injections, or two injections a day. After four years, the patients were free to choose their treatment, and therefore the data were analyzed according to mean HbA1 during seven years. The mean HbA1 was 11.2% (2.2) (SD) at start, and 9.5% (1.5) at seven years, which was a significant long term improvement (P less than 0.001). Eight out of 10 patients with mean seven year HbA1 less than 8.5% improved their albumin excretion rate, and patients with mean HbA1 greater than 10% had an increased albumin excretion rate (from 26 mg/24 hr to 91 mg/24 hr, P less than 0.02). The glomerular filtration rate decreased slightly regardless of mean HbA1 level. Systolic blood pressure increased significantly regardless of mean HbA1. Diastolic blood pressure was unchanged in the patients with mean HbA1 less than 10%, but increased slightly (NS) in patients with HbA1 greater than 10%. We conclude that mean blood glucose as measured by glycosylated hemoglobin is a main determinant in the progression of urinary albumin excretion in insulin dependent diabetics, and near normoglycemia improves urinary albumin excretion. PMID- 1513114 TI - Simultaneous pancreas-kidney transplant versus kidney transplant alone in diabetic patients. AB - The decision for simultaneous pancreas-kidney (SPK) versus kidney transplant alone (KTA) in diabetic patients with renal failure depends on the potential risks and benefits for each procedure. The purpose of this study was to compare the morbidity, mortality, and renal allograft survival in diabetic patients who underwent SPK versus KTA, and to discern the added risks associated with pancreas transplantation. Between 7/1/86 and 9/30/90, 69 primary cadaver SPK and 59 primary cadaver KTA were performed in type I diabetic patients with chronic renal failure. Antilymphocyte globulin or OKT3 was used for induction therapy, followed by standard triple therapy (prednisone, azathioprine, and cyclosporine). Patient and graft survivals were retrospectively analyzed. In addition, a detailed comparison of morbidity in those patients treated after 7/1/87 was performed (53 SPK, 49 KTA). For those less than 45 years of age (65 SPK, 42 KTA), there were no significant differences (P greater than 0.6) in the actuarial patient survival at one year (SPK 92%, KTA 95%), or two years (SPK 89%, KTA 92%), or actuarial renal allograft survival at one year (SPK 82%, KTA 83%) or two years (SPK 77%, KTA 83%). However, for those greater than 45 years old, actuarial renal allograft survival was significantly higher (P less than 0.03) in the KTA group. The mean serum creatinine levels were similar at one year (SPK 1.8, KTA 1.9 mg/d).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1513115 TI - Intrarenal distribution of clusterin following reduction of renal mass. AB - Clusterin is a multifunctional protein isolated from a number of tissues in several different species. In a variety of renal diseases, clusterin appears in the glomerulus and tubules in association with the membrane attack complex of complement. It is also transiently expressed after several forms of acute renal injury. In this study, we examined the expression and intrarenal distribution of clusterin following subtotal renal ablation. Male rats were subjected to either 1 1/3 nephrectomy (1-1/3 NX), uninephrectomy (UNX) or sham operation (SHAM). Two weeks after surgery, clusterin mRNA was elevated in the 1-1/3 NX group (1-1/3 NX: 1215 +/- 88; UNX: 208 +/- 11; SHAM: 207 +/- 19 OD units; P less than 0.001). Clusterin mRNA increased between 3 and 24 hours after 1-1/3 NX, plateaued, and remained elevated for at least seven weeks. The increased clusterin mRNA in 1-1/3 NX was localized to the tissue adjacent to the infarctive scar (scar 858 +/- 173 vs. non-scar 98 +/- 27 OD units; P less than 0.001). Clusterin protein followed a similar pattern of localization, being increased in most tubules and some peritubular capillaries in the peri-infarct zone. Only occasional tubules were positive for clusterin in the renal tissue distant from the scar or in the kidneys of sham operated rats. Co-localization of clusterin and C5b-9 was not detected. Evidence for apoptosis was found in the peri-infarct zone but not elsewhere in 1-1/3 NX kidney or in the normal kidney following sham operation. Infarction of 1/3 of the left kidney without contralateral nephrectomy, a maneuver which eliminates the compensatory growth, and uremia seen with 1-1/3 NX still resulted in increased clusterin mRNA in the infarcted left kidney compared to the intact right kidney (LK: 790 +/- 112 vs. RK: 128 +/- 25 OD units; P less than 0.001), although the amount of clusterin mRNA was less than that found following 1-1/3 NX. In conclusion, persistently increased clusterin mRNA and protein was seen in the peri-infarct zone following 1-1/3 NX. This increased expression of clusterin may be playing a role in the ischemia-related apoptosis present in the scar-adjacent tissue. PMID- 1513116 TI - HIV infects glomerular endothelial and mesangial but not epithelial cells in vitro. AB - The infectivity of human immunodeficiency virus (HIV-1) in human glomerular cells was evaluated by exposing homogeneous cultures of human glomerular capillary endothelial, mesangial and epithelial cells to HIV in vitro. Infectivity and HIV expression was assessed by: 1) the measurement of p24 antigen production from culture supernatants; 2) the presence of p24 antigen intracellularly by immunofluorescence; 3) levels of P24 antigen production or syncytia formation following the cocultivation of glomerular cells exposed to HIV with normal human peripheral blood mononuclear cells or MT-2 lymphocytes; and 4) the presence of intracellular HIV DNA by polymerase chain reaction. The results indicate that HIV can infect and replicate in glomerular capillary endothelial cells and in a small percentage of mesangial cells, but not in human glomerular epithelial cells in vitro. PMID- 1513117 TI - Improved left ventricular contractility with cool temperature hemodialysis. AB - Cool temperature dialysis (CTD) has been shown to sharply decrease the frequency of intradialytic hemodialysis hypotension, but the mechanism of this hemodynamic protection is unknown. Therefore, we performed two-dimensional echocardiographic studies of left ventricular contractility in six stable hemodialysis patients before and after hemodialysis at 37 degrees C (RTD) and 35 degrees C (CTD). Left ventricular function was assessed by plotting the rate-corrected velocity of circumferential fiber shortening (Vcfc) against end-systolic wall stress (sigma es) at four different levels of afterload. Linear regression was used to calculate Vcfc at a common afterload of 50 g/cm2. Changes in weight and dialysis parameters were similar following RTD and CTD. Mean arterial pressure and heart rate did not change significantly following RTD or CTD. The Vcfc - sigma es relation was shifted upward in each patient after CTD, indicating increased contractility as compared to RTD or pre-dialysis baseline. Pre-dialysis Vcfc at an afterload of 50 g/cm2 was similar during RTD and CTD (0.94 +/- 0.24 circ/sec vs. 0.92 +/- 0.22 circ/sec). Postdialysis Vcfc at an afterload of 50 g/cm2 was significantly higher for CTD than for RTD (1.13 +/- 0.29 circ/sec vs. 0.98 +/- 0.30 circ/sec, P = 0.0004). Thus, cool temperature dialysis increases left ventricular contractility in hemodialysis patients, which may be a potential mechanism whereby hemodynamic tolerance to the dialysis procedure is improved. PMID- 1513118 TI - Renal hypertrophy in streptozotocin diabetic rats: role of proteolytic lysosomal enzymes. AB - Renal protein mass increases in diabetic renal hypertrophy. Accretion of protein may be the result of increased protein synthesis and/or decreased protein degradation. The lysosomal proteases, cathepsins B and L, are key enzymes in cellular protein catabolism. To evaluate the role of protein degradation in diabetic renal hypertrophy, the activities of cathepsins B and L were measured in microdissected proximal tubule segments and in kidney cortex homogenates. In rats four and ten days following induction of diabetes by streptozotocin, the kidney weight was increased and the cathepsin activities were reduced in proximal tubule segments. Treatment with insulin prevented both changes. The liver weight in diabetic rats was decreased and the activity of cathepsins B and L was increased, while the activity in kidney cortex was reduced. This excluded that diabetes per se may be accompanied by decreased cathepsin activities independent of organ hypertrophy. Renal hypertrophy as a cause rather than as the consequence of reduced cathepsin activities was excluded by the finding of unchanged cathepsin activities in proximal tubule segments from rats with compensatory renal hypertrophy four days and ten days following unilateral nephrectomy. Decreased activities of cathepsins B and L may reflect decreased intracellular protein degradation. Decreased protein breakdown in proximal tubules may contribute to diabetic renal hypertrophy. In agreement with this interpretation are the results from rats six months following induction of diabetes. Renal hypertrophy is complete at that time. No further accretion of protein occurs and the cathepsin activities in the proximal tubule were not different from controls. PMID- 1513119 TI - Sphingomyelin and cholesterol modulate sodium coupled uptakes in proximal tubular cells. AB - Sphingomyelin (SM) and cholesterol are major lipid species of apical membranes in renal proximal tubular cells and confer to these membranes a low fluidity. Changes in membrane fluidity and/or lipidic composition were shown to affect the activity of cotransport systems of renal apical membranes. We evaluated the effect of decreasing membrane SM content on lipidic composition, membrane fluidity and sodium (Na)coupled uptakes in rabbit proximal tubular cells in primary culture. Sphingomyelinase (SMase) (30 to 250 mU/ml) decreased [3H]choline labeled SM content, decreased cholesterol content, and increased cholesterol esterification. SMase did not modify membrane fluidity on isolated brush border membranes. SMase decreased Vmax of Na-dependent uptake of phosphate and alpha methyl-D-glucoside, but not of alanine. SMase did not influence protein kinase C induced inhibition of phosphate and glucose uptake. Increasing membrane cholesterol content with cholesterol-enriched liposomes subsequently to SMase action restored in part glucose uptake, but not phosphate uptake. In conclusion, SM degradation affected Na-phosphate and Na-glucose cotransports through changes in both SM and cholesterol contents of apical proximal membranes; these changes seemed to occur independently from changes in bulk membrane fluidity. These results suggest that SM and cholesterol have distinct and intricated roles in accessibility and/or activity of apical cotransport systems. PMID- 1513120 TI - [Vision disorders in children with acquired severe brain damage]. AB - 27 children with severe brain injuries were examined by an ophthalmologist and had several paediatric examinations during an eight or ten weeks' course of rehabilitation. With highly reduced levels of consciousness they had hardly any cortical visual function but frequently had brainstem controlled reactions of eyelids, pupils and eyeballs. The development of these reactions was followed up and correlated to the recovering visual functions. Some of the palpebral reflexes seemed to be of prognostic significance to the reappearance of cortical visual functions. PMID- 1513121 TI - [Corneal sensibility following epikeratophakia]. AB - The postoperative rate of reinnervation following corneal surgery is widely considered to be a useful indicator of the healing process. This study reports the corneal sensitivity of 14 patients following epikeratophakia for different indications (myopia, aphakia and keratoconus) after time periods ranging from 7 to 104 weeks. All transplants were clear at the time of measurement. A newly developed aesthesiometer (using a low electric current for stimulation) was employed. Nine positions on the operated eye were chosen for the measurements, five locations of the non-operated fellow eye served as controls. On the operated eye the corneal sensitivity peripheral to the trephination were significantly reduced at the 9 and 12 o'clock positions as compared to the other eye. The 3 and 6 o'clock locations showed no significant difference. On the epikeratophakia lenticule the sensitivity was significantly reduced at all points, the center showing the largest difference (p less than 0.001). No correlation with age, sex or the indication for the procedure was observed. Although there was a trend of a positive correlation between the postoperative time period and the central corneal sensitivity, the follow-up was too short to reach significant levels. The nearly complete lack of corneal sensitivity, particularly in the center of the transplant is therefore well compatible with its long-time survival, even when the lenticule has been prepared with the cryolathe and lyophilized for transportation. PMID- 1513122 TI - [Localization disorders in squint amblyopia: horizontal line bisection and relative vertical localization]. AB - We used two different procedures for the evaluation of spatial localization errors in strabismic and anisometropic amblyopes, strabismic alternators and normal control subjects: partitioning of horizontal lines and vertical alignment. We found defective spatial localization in the amblyopic eyes of squinters with both procedures. However, in the horizontal partitioning experiment, the control subjects also showed asymmetries between the two hemifields. Thus, there is no good baseline under these conditions for the results of the amblyopic eyes of squinters. Our results show that vertical alignment is the more appropriate procedure to quantify defective spatial localization in strabismic amblyopes. PMID- 1513123 TI - [The influence of some ophthalmologists of German origin on the development of American ophthalmology]. AB - German-speaking immigrants came to America at the end of the seventeenth century from Central Europe, in the 19th century predominantly from Germany, in the 20th century from the Austro-Hungarian Monarchy. Herrmann Knapp (1839-1911), 1859 member of Eye Department in Heidelberg, 1867 immigration, 1879 foundation of American Archives of Ophthalmology, continued to be Editor together with his son Arnold until 1948. Julius Homberger (1839-1872), born in Frankfurt, 1861 immigration, foundation of American Journal of Ophthalmology (1862-1865). Favored specialisation in medicine, Secretary of Section of Surgery in the new American Medical Association 1864, expelled 1868. Adolf Alt (1851-1920), 1875 graduation at the University in Heidelberg, 1875 immigration, 1879 publication of his book in English and German "The Normal and Pathological Histology of the Human Eye". In 1883 second foundation of the American Journal of Ophthalmology, 1896 first president of Western Ophthalmological Society, 1882 member of American Ophthalmological Society. Karl Koller (1857-1944) from Bohemia, 1882 graduation in Vienna, 1884 discovery of anaesthetic effect of cocaine, 1888 immigration, 1889 chief of Mount Sinai Hospital, 1922 Howe-Medal, member of American Ophthalmological Society. Ludwig von Sallman (1892-1975), 1919 graduation in Vienna, 1939 immigration, head of Laboratories of Hermann Knapp Memorial Hospital, New York, 1956 chief of National Institute of Neurological Diseases and Blindness, Bethesda, 1947 member of American Ophthalmological Society, 1959 Howe Medal. Bertha A. Klien-Montcreiff (1898-1978), 1925 graduation in Vienna, 1928 immigration to Chicago, 1959 Professor at the University of Chicago, clinicopathological correlation of ophthalmoscopic and histologic findings in oil paintings.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1513124 TI - [Christmas tree ornament cataract--an indication for disordered lipid metabolism?]. AB - Cataract combined with Christmas tree decoration crystals in the lens is a relatively rare but very impressing cataract formation. The aim of this controlled study was to give an answer to the question, whether cholesterol level in blood is as important for local cholesterol accumulation in the lens as it is for the mechanism of arteriosclerosis. The blood levels of cholesterol, triglyceride, HDL and LDL were examined in 35 patients (average age 83.5 years; 26 women, 9 men). There was no significant difference between these parameters and those of a control group, which is similar in age and sex proportion. Therefore it is presumed, that these crystals of cholesterol are a result of lens metabolism and not of hypercholesterolemia. PMID- 1513125 TI - [Taenia crassiceps in the anterior chamber of the human eye. A case report]. AB - An otherwise healthy 15-year-old girl developed an iridocyclitis in her right eye. A contractable living parasite measuring two millimeter could be detected in the anterior chamber, the other parts of the eye remained uninvolved. The patient had close contact with the young dog of the family. By using a viscoelastic substance the parasite could be removed alive without any complications. The tapeworm was found to be too young for having developed the characteristic scolex. Western-immunoblotting gave indirect evidence for infection with Taenia crassiceps, a dog's tapeworm. During an observation period of two years no evidence for any other ocular or general Taenia crassiceps infestations could be found. PMID- 1513126 TI - [Surgical treatment of hyperplastic persistent pupillary membrane]. AB - Clinical findings of two patients with persisting pupillary membranes are described and therapy is discussed. The indication for excision of the pupillary membrane was constituted in one patient (age 6 weeks) by complete occlusion of the optic axis, in the second (age 4 months) by absence of any recordable fixation. In both cases the pupillary membrane could be separated from the anterior lens capsule without lens damage. No strabismus or lens opacification were detected postoperatively. Surgery was undertaken with the intention of avoiding primary lentectomy, since pupillary membranes can usually be separated easily from the anterior lens capsule with viscoelastic substances. PMID- 1513127 TI - [Cysteamine eyedrops for treatment of corneal cysteine deposits in infantile cystinosis]. AB - A two-year-old boy with nephropathic cystinosis was successfully treated with cysteamine eye drops. Using topical cysteamine 0.1% every two hours in the right eye we found a clearance of crystals from the cornea after 26 weeks. In the left eye, treated with topical cysteamine 0.5% the same result was reached after 12 weeks. PMID- 1513128 TI - [On the occasion of the 75th anniversary of the death of Theodor Leber. Theodor Leber 1840-1917. Markers of professional achievement with excerpts from his diaries and correspondence]. PMID- 1513129 TI - [Arthur von Hippel--100 years motorized trepanation]. AB - The introduction of a new motorized trepan in ophthalmic surgery by Arthur v. Hippel in 1891 was a very important achievement. The corneal incision became much safer and the unintentional injury of the iris, the lens and the vitreous body could be avoided considerably. Following a statement on corneal grafting in the 2. part of the 19. century the development of the trepan, the technical data and the experiences and reactions of other ophthalmic surgeons are discussed. The innovations of Arthur v. Hippel were appreciated by the A. v. Grafe-Prize of the Society of Ophthalmology/Heidelberg. PMID- 1513130 TI - [Berlin-Brandenburg Ophthalmologists' Association meeting. December 7-8, 1991. Abstracts]. PMID- 1513131 TI - [The cycloplegic effect of atropine in comparison with the cyclopentolate tropicamide-phenylephrine combination]. AB - Atropine is thought to produce the most effective cycloplegia in early childhood. Cyclopentolate and Tropicamide are the best known short acting cycloplegic agents. Phenylephrine is an adrenergic agent and has also a cycloplegic effect. In this study we compared a combination of Cyclopentolate, Tropicamide and Phenylephrine with Atropine and observed no difference between them. PMID- 1513132 TI - CAD-design, stress analysis and in vitro evaluation of three leaflet blood-pump valves. AB - The computer-supported development of valves for cardiac-assist devices or artificial hearts is shown in relation to plastic technology. A CAD-system is used for the design development, whereas the dimensioning of the critical and highly stressed membranes is examined by FEM-analyses. Economic manufacture is permitted by the combined thermoforming-dip moulding technique; the blood-side components are made from biocompatible polyurethane to minimize blood damage. The first long-term results in the test set-up are compared to the FEM results. PMID- 1513133 TI - Blood analysis using black and white digital images. AB - Image processing offers a powerful tool for medical diagnosis by visual inspection. Our proposed system considers the blood analysis problem. The system processes black and white blood images obtained from a CCD camera through a microscope. Different categories of cells are recognized, counted and classified into white cells, red cells and blood petals. The white cells are further treated for their classification, according to the morphological characteristics of their nuclei. The final classification is printed in special format for the physician. PMID- 1513134 TI - Bending moments in lower extremity bones for two standing postures. AB - The goal of this paper is to study how external gravitational forces stress the lower extremity bones and to ascertain and study how muscle activation compensates for the external load. For these purposes relatively accurate anatomical and biomechanical modelling is necessary. For a comparison of the calculated results to the naturally occurring muscular activity, seven-channel surface EMG activity was recorded. For simplicity a two-dimensional model was developed for the sagittal plane including 19 lower extremity muscles relevant to human standing and walking. In the calculation procedure of muscle forces an optimization procedure is also included. The results give rise to the expected assumption that muscle action is covered by two main requirements: first, to stabilize the joint actively (moment equilibrium) and, second, to compensate efficiently for bending moments produced by gravitational and external forces. PMID- 1513135 TI - Non-invasive optical monitoring of cerebral blood oxygenation in the foetus and newborn: preliminary investigation. AB - Near infra-red spectroscopy was applied as a non-invasive and continuous technique for the in vivo monitoring of blood and tissue oxygenation in human neonates. Monitoring of cerebral blood oxygenation in the wavelength range 775 904 nm was carried out on preterm infants after inducing a transient mild hypoxic change; the measurements were performed either by the transmission or reflection (backscattering) mode of monitoring. The results of these investigations were used to assess the application of the technique to foetal monitoring. A series of foetal monitoring studies was performed to investigate the influence of maternal contractions on foetal cerebral blood oxygenation. Although only changes in haemoglobin concentration can be monitored at present, the results suggest that near infra-red monitoring could provide a non-invasive, real-time monitoring method in intensive neonatal and intrapartum care. PMID- 1513136 TI - Periodic posture stimulation of the baroreceptors and the local vasomotor reflexes. AB - In a supine subject, lowering of the foot from heart level to 50 cm below is known to stimulate the local reflex response and the baroreceptor outflow. We lowered and raised the leg of a supine subject periodically, with the leg stationary between movements (square wave). The Traube-Hering-Mayer wave (THM congruent to 0.1 Hz) was captured by or locked on to the leg movement over a certain frequency range, this is usually called the entrainment range. Square wave periodic leg movement in this manner on 10 male subjects, mean age 22 years, demonstrated that the THM frequency can be entrained. The lower limit of the entrainment bandwidth is 0.0841 (SD 0.0030) Hz and the upper limit is 0.1176 (SD 0.0013) Hz. Further examination showed that this phenomenon is independent of the breathing input. Comparison with the Traube-Hering-Mayer entrainment techniques of breathing and periodic neck suction using the Eckberg collar which stimulates the baroreceptors showed similar results. This work supports the hypothesis that the local reflex response and the baroreceptor outflow entrain the THM frequency. PMID- 1513137 TI - Patterns of relations between lower limb angle excursions during normal gait. AB - This paper deals with the analysis of data from a kinematic study of limb angle during normal gait. The first set of data deals with the variation of femur angle to the vertical, and of knee and ankle flexion-extension. The data are recorded on the System of Gestual Automatic 3D Analysis with a 50 Hz sampling rate. The second data set concerns morphological parameters. The data are obtained from 35 subjects. The time angle data are raw and are not to be related to a base position. The first stage of the angle analysis shows that a walking cycle can be characterized by 25 values. A factor analysis is then applied to these values for each angle in order to underscore the more informative instants. From this study, eight measurements are preserved. In the third stage, the same method is applied to both angles. It illustrates four ways to differentiate healthy subjects' walk. It also shows that the angles of femur and knee are strongly correlated and that there is a priori no clear relationship between the ankle and the two previous angles. The last stage is analysis of the morphological and angle parameters together. It brings to the fore the influence of sex and height for two groups of subjects. PMID- 1513138 TI - Artificial vision approach to the understanding of heart motion. AB - To overcome the major drawbacks of conventional descriptive methods, we have developed a computer vision approach to aid understanding of heart motion from a series of sequential X-ray images. The computation is addressed of local descriptors of the heart pumping function from ventricular contours. Physical constraints are exploited such as spatial smoothness of the displacement field and shape correspondence between ventricular boundaries during the beat. A computational method is proposed for the estimation of the displacement field of the left ventricular boundary. Moreover, the spatial arrangement of the estimated motion field is rendered explicit so that it may be utilized in the medical clinic (or for high-level symbolic processing). This is achieved using a grouping criterion which allows the clustering of contiguous points of the left ventricular outline into curve segments which have homogeneous motion properties. PMID- 1513139 TI - Effects of tibial rotations on patellar tracking and patello-femoral contact areas. AB - The object of this study is to determine the effect of tibial rotations on the three-dimensional patello-femoral motions and contact areas during a physiological loading condition, the knee-extension exercise. A commercially available device, the 3-SPACE digitizer and tracker system, was used to collect the motion data, utilizing cadaveric human lower limbs as well as the geometric measurements describing the articular surfaces at the patello-femoral joint. It was found that tibial rotations caused statistically significant differences, at the 0.05 level, in patellar tilt, patellar rotation and patellar medial-lateral shift. It was also found that while the magnitude of the total contact area at a given knee flexion angle did not change significantly with tibial rotations, medial and lateral components of the total contact areas were affected by tibial rotations. Medical femoral contact areas increased with internal tibial rotations at all flexion angles; lateral femoral contact areas increased with external tibial rotations at all flexion angles. This correlates well with the kinematic data since it was found that the patella shifted medially with internal tibial rotations at all flexion angles, and titled more medially near full-extension causing an increase in the medial contact areas and a decrease in the lateral contact areas. PMID- 1513140 TI - Energetics of paraplegic walking. AB - A group of 35 paraplegic subjects using reciprocating walking orthoses have been examined in order to gain an insight into the potential functional benefits of using such devices. Measurements have been made of walking speeds and of the energy costs of ambulation using an established technique based on heart rate recordings. It was found that orthotically aided walking for paraplegics was slow and energy costly compared with both normal walking and wheelchair propulsion and, as it additionally requires the use of a walking aid in both hands, cannot be considered to confer the functional benefits frequently claimed for it. Nevertheless, the majority of the subjects studied liked their orthosis and did well in it, with many subjectively reporting improvements in mobility and independence. PMID- 1513141 TI - Self-propelled weight-relieving walker for gait rehabilitation. AB - This paper describes a novel walking aid, the weight relieving walker (WRW), which partially relieves the body weight of an ambulating patient. The device incorporates a pneumatic weight relief mechanism, a restraint mechanism and a forward propulsion mechanism. Weight relief facilitates stance on an affected lower limb as well as the swing of that same limb. Restraint of the patient by the walker adds to trunk stability thereby facilitating walking movements of the lower extremities. A motorized, self-propelled walker neutralizes the effect of the walker's own weight on patient's locomotion. Additionally, it contributes to step symmetry. Data gathered from 26 patients with severe locomotion problems, point to a substantial contribution of the device to ambulation. PMID- 1513142 TI - Finger tremor and the central nervous system. AB - It is well known that normal physiological tremor of the fingers and alpha rhythm in the EEG, may share a common frequency band in the region of 10 Hz; that these two characteristics may be in some way related as a function of their frequencies, is a hypothesis which needs to be tested, as one element in establishing the physiology of physiological tremor. Bilateral occipital EEGs and simultaneous measurements of acceleration from the terminal phalanx of the middle finger of both hands were recorded from eight subjects. The data were analysed to produce power spectral densities and coherence functions, the latter being used to reveal the presence or absence of frequency elements common to both signals. No evidence was found that would support a hypothesis that the two characteristics were in any way frequency related, from which it can be inferred that the tremor is not under central control. In addition, tremor of the right and left hands does not show a synchronous relationship. PMID- 1513143 TI - Comments on 'Response of human femur to mechanical vibration'. PMID- 1513144 TI - Ventricular assist devices for postcardiotomy cardiogenic shock. A combined registry experience. AB - Data submitted voluntarily to the combined registry since its inception in 1985 to December 31, 1990, on the use of ventricular assist devices for postcardiotomy cardiogenic shock in 965 patients were analyzed. Approximately 45% of patients were weaned from temporary circulatory assistance and 24.6% reached hospital discharge regardless of the original operation. In 90% of patients who were discharged from the hospital, circulatory support was able to be discontinued by 1 week. Rates of weaning and discharge were statistically different and favored those patients requiring univentricular support only. Results were equal whether nonpulsatile centrifugal or pulsatile pneumatic devices were used for support. Although complications were frequent and multiple during assist pumping, patient variables including age greater than 70 years rather than direct complications caused by circulatory support were likely to affect overall outcome. In patients achieving hospital discharge, 2-year actuarial survival was 82% with 86% of patients being in New York Heart Association functional class I or II. In rare instances of device dependency in 43 patients (4.5%) with no contraindications to transplantation, 32 (74.4%) underwent bridge to cardiac transplant and 20 (62.5%) were discharged. This multi-institutional experience would continue to support the use of ventricular assist devices in postcardiotomy cardiogenic shock. PMID- 1513145 TI - Experience with the Sarns centrifugal pump in postcardiotomy ventricular failure. AB - The reported clinical use of the Sarns centrifugal pump (Sarns, Inc./3M, Ann Arbor, Mich.) as a cardiac assist device for postcardiotomy ventricular failure is limited. During a 25-month period ending November 1988, we used 40 Sarns centrifugal pumps as univentricular or biventricular cardiac assist devices in 27 patients who could not be weaned from cardiopulmonary bypass despite maximal pharmacologic and intraaortic balloon support. Eighteen men and nine women with a mean age of 60.4 years (28 to 83) required assistance. Left ventricular assist alone was used in 12 patients, right ventricular assist in 2, and biventricular assist in 13. The duration of assist ranged from 2 to 434 hours (median 45). Centrifugal assist was successful in weaning 100% of the patients. Ten of 27 patients (37%) improved hemodynamically, allowing removal of the device(s), and 5 of 27 (18.5%) survived hospitalization. Survival of patients requiring left ventricular assist only was 33.3% (4/12). Complications were common and included renal failure, hemorrhage, coagulopathy, ventricular arrhythmias, sepsis, cerebrovascular accident, and wound infection. During 3560 centrifugal pump hours, no pump thrombosis was observed. The Sarns centrifugal pump is an effective assist device when used to salvage patients who otherwise cannot be weaned from cardiopulmonary bypass. Statistical analysis of preoperative patient characteristics, operative risk factors, and postoperative complications failed to predict which patients would be weaned from cardiac assist or which would survive. PMID- 1513146 TI - Mechanical assistance of the left ventricle: acute effect on cardiac performance and coronary flow of different perfusion patterns. AB - Mechanical circulatory assistance by ventricular assist devices provides an opportunity to influence the aortic pressure pattern, which may affect ventricular loading and coronary perfusion. The effect of synchronous, pulsatile coronary perfusion of an assist device-supported left ventricle has not been studied. To analyze the effect of different perfusion patterns on left ventricular performance and on coronary flow, independent of pressure and volume loading, we used three different modes of aortic perfusion in an isometric, contracting, isolated canine heart model. The effect of nonpulsatile, counter pulsatile, and copulsatile coronary perfusion was analyzed in four subgroups to simulate different, clinically relevant situations (using two different ventricular end-diastolic volumes [normal and high] and two mean perfusion pressures [normal and critically low]). Our experiments demonstrated that total coronary flow is optimized by making the perfusion pressure pulsatile and by synchronously timing the pump systole with ventricular diastole (counterpulsation). Under identical conditions of preload and mean perfusion pressure, coronary flow and left ventricular contractility were decreased during non-pulsatile and copulsatile aortic perfusion when compared with counterpulsatile flow. There were no significant differences between the nonpulsatile and copulsatile modes. We conclude from these data that a nonejecting, but contracting, left ventricle will have improved systolic function and coronary blood flow if the coronary perfusion pressure is synchronized in a counterpulsatile manner. This is a significant implication for mechanical left ventricular assist devices when used to promote myocardial recovery. PMID- 1513147 TI - Right heart function during prosthetic left ventricular assistance in a porcine model of congestive heart failure. AB - A left ventricular assist device was used to produce a 90% reduction in peak systolic left ventricular pressure in pigs with congestive heart failure, and the resultant effects on right ventricular function were determined. Initially, eight farm pigs underwent rapid ventricular pacing at 230 beats/min for 7 days to produce congestive heart failure. When compared with an independent series of normal pigs, cardiac output in the paced animals was 33.3% less (2.2 +/- 0.2 versus 3.3 +/- 0.5 L/min; p less than 0.05), left ventricular end-diastolic pressure was elevated (13.8 +/- 3.5 versus 6.6 +/- 1.8 mm Hg; p less than 0.05), and the slope of the right ventricular global stroke work curve was significantly depressed (0.004 +/- 0.001 versus 0.033 +/- 0.003 joules/mm Hg; p less than 0.05). Next, the left ventricular assist device was connected between left ventricular apex and ascending aorta and left ventricular pressure was reduced from 92.0 +/- 3.8 to 10.5 +/- 2.2 mm Hg, while systemic arterial pressure was maintained constant. This led to a further impairment in cardiac output (-14%), mean arterial pressure (-15%), and the slope of the right ventricular global stroke work curve (-50%). Under each condition, right ventricular preload recruitable stroke work and end-systolic pressure-dimension relationships were studied in three different regions on the right ventricle during both steady state and transient inferior vena caval occlusion. In the right ventricular septal-free wall dimension, left ventricular pressure unloading resulted in a 47.5% +/- 5.4% (p less than 0.05) reduction in the slope and 20.1% +/- 4.8% (p less than 0.05) increase in the dimension intercept of the preload recruitable stroke work relationship. There was also a 44.6% +/- 4.8% (p less than 0.05) reduction in the slope and 15.6% +/- 2.8% (p less than 0.05) increase in the dimension intercept of the end-systolic pressure-dimension relation. These slope changes plus reductions in cardiac output and in global stroke work, which are indicative of impaired right ventricular function during left ventricular pressure unloading in the congestive heart failure pigs, are not seen in normal hearts, whereas the intercept changes associated with leftward septal shift are present in both. These results suggest that anatomic ventricular interactions have a more significant role in heart failure than in the normal heart in determining overall right ventricular function during left ventricular assist device support. PMID- 1513148 TI - Venoarterial extracorporeal membrane oxygenation--how safe is it? Evaluation with a new experimental model. AB - This study was undertaken to find out if about 25% right cardiac output is sufficient for preservation of lung function during prolonged periods of venoarterial extracorporeal membrane oxygenation. Six healthy pigs weighing 57 kg were subjected to 18-hour venoarterial extracorporeal membrane oxygenation. During this period 1200 ml/min venous blood was delivered to the lungs through the pulmonary artery with the help of a separate roller pump and with use of the animal's own right ventricle to generate the pulse. Animals were observed for 6 hours after weaning from the venoarterial extracorporeal membrane oxygenation. At the sixth hour after extracorporeal membrane oxygenation, arterial oxygen tension, venous oxygen tension, lung compliance, and cardiac output had decreased significantly. Pulmonary vascular resistance and pulmonary clearance of technetium 99m-diethylenetriamine pentaacetic acid increased significantly also. The systemic arterial and venous carbon dioxide tensions, pH, and the base excess remained unchanged, as did the blood pressure and the systemic vascular resistance. Histopathology of the lung specimens revealed focal alveolar wall thickening and alveolar capillary congestion. The major portion of the pulmonary parenchyma looked normal. Alterations in pulmonary parameters cited were, to a major extent, explained on the basis of the experimental protocol followed and were believed to be reversible. This study suggests that about 25% of the systemic cardiac output should be diverted into the pulmonary artery for prevention of irreversible physiologic and histopathologic changes in the lungs during 18-hour normothermic venoarterial extracorporeal membrane oxygenation in healthy juvenile pigs. PMID- 1513149 TI - Prevention of postoperative pericardial adhesions by closure of the pericardium with absorbable polymer patches. An experimental study. AB - Pericardial adhesions after cardiac operations are a widely known phenomenon. They may severely complicate reoperations, making reentry hazardous, increasing bleeding, and prolonging the operation time. The anatomic orientation and visibility of both bypass grafts and coronary arteries are also impaired. With the aim of minimizing pericardial adhesions after cardiac operations, we studied the course of tissue regeneration after implantation of a new absorbable patch made from poly-hydroxy-butyrate. A total of 23 sheep were studied. Of these, 18 formed the test group and five served as control animals. The animals were killed at intervals of 2 to 30 months after the operation. In 14 of the 18 test animals no adhesions developed. In three animals loose adhesions were found, and in one with signs of postoperative infection there were moderate, generalized adhesions. All control sheep showed moderate adhesions; no infection was noted in this group. Light microscopy in the test group revealed a layer of mesothelium-like cells facing the epicardial side; this was already present in the early specimens. Poly-hydroxy-butyrate appeared to be slowly phagocytosed by polynucleated macrophages, which were still found occasionally in the late samples. Lymphocytes and platelets were rare. Scanning electron microscopy showed, on the epicardial side of the regenerated tissue, a mesothelium-like lining that completely covered the underlying collagen layer. The surface cell morphology grossly resembled that of native pericardium. It was concluded that in this animal model poly-hydroxy-butyrate pericardial patches decreased adhesions and preserved coronary anatomy. The findings in the control group demonstrated that pericardial surgery in the sheep was associated with adhesion formation. PMID- 1513150 TI - Myocardial protection during cardiac operations. Decreased morbidity and lower cost with blood cardioplegia and coronary sinus perfusion. AB - The efficacy of myocardial protection with a single aortic crossclamp and blood cardioplegia was evaluated in 819 consecutive patients stratified for preoperative condition by means of a new clinical risk scoring system. A protocol using either antegrade or antegrade/retrograde blood cardioplegia was compared with antegrade crystalloid cardioplegia in 2582 similar, consecutive, and concurrent patients. In the blood cardioplegia cohort, 97 (11.8%) patients had 129 complications compared with 407 (15.8%) patients and 675 complications in the crystalloid cardioplegia group (p = 0.006). In high-risk patients, combined antegrade/retrograde cardioplegia significantly reduced myocardial infarction, stroke, and respiratory and wound complications. Despite the significantly longer aortic crossclamp time required for blood cardioplegia, patients undergoing crystalloid cardioplegia were 1.7 (95% confidence interval 1.3, 2.1) times more likely to have a morbid event. Time in the intensive care unit, length of hospitalization, and length-of-stay outlier status were significantly decreased in the blood cardioplegia compared with the crystalloid cardioplegia group. The net savings in hospital cost amounted to $2196 per case. When compared separately with crystalloid cardioplegia, combined antegrade/retrograde blood cardioplegia accounted for most of the morbidity reduction by significantly reducing perioperative myocardial infarction, wound complications, and length of stay in patients having reoperations. Antegrade/retrograde blood cardioplegia did not influence 1-year survival or event-free survival, even when risk was considered. PMID- 1513151 TI - Salvage of ischemic myocardium by nonsynchronized retroperfusion in the pig. AB - Salvage of ischemic myocardium, with the aid of a nonsynchronized coronary sinus retroperfusion system, was studied in a pig infarct model. In anesthetized open chested animals, the left anterior descending coronary artery was occluded for 4 hours and then reperfused for 1 hour before the animals were killed. In the control group (n = 12) no therapy was used. In the experimental group (n = 13), nonsynchronized retrovenous coronary sinus perfusion was applied during the 4 hours of coronary artery occlusion. Therapy consisted of intermittent balloon occlusion of the coronary sinus (5-second inflation, 5-second deflation) with retroperfusion of arterial blood at 60 ml/min during the inflation part of the cycle. Infarct size, expressed as a percentage of the area at risk (+/- standard deviation), was significantly smaller in the experimental group (41.5% +/- 15.0%) than in the control group (80.5% +/- 6.1%) (p less than 0.001). Mean coronary sinus pressure (+/- standard deviation) was 51 +/- 12 mm Hg in the experimental group but was not elevated in the control animals. We conclude that nonsynchronized retrovenous coronary sinus perfusion was able to significantly salvage ischemic myocardium in a model of minimal intercoronary collateral circulation. PMID- 1513152 TI - Topical cardiac hypothermia in patients with coronary disease. An unnecessary adjunct to cardioplegic protection and cause of pulmonary morbidity. AB - This retrospective analysis tests the hypothesis that topical cardiac hypothermia is an unnecessary adjunct to intraoperative myocardial protection and an avoidable cause of pulmonary morbidity in patients with coronary disease receiving blood cardioplegia. The hospital records of 150 nonrandomized consecutive patients undergoing elective and emergency isolated coronary revascularization were reviewed. All patients received multidose cold blood cardioplegia followed by warm blood cardioplegic reperfusion distributed through grafts. Fifty patients received iced slush, 50 received topical 4 degrees C saline, and no topical cooling was used in 50 others. Patients groups were comparable in number of grafts (3.7 versus 3.5 versus 3.5) and crossclamp time (61 versus 62 versus 61 minutes). More emergency operations were performed in the patients receiving no topical hypothermia (12/50 versus 8/50 versus 7/50). Postoperative x-ray films were reviewed by a radiologist who did not know of patient grouping. Postoperative results were comparable in hemodynamics, inotropic requirements (10/50 ice versus 8/50 saline versus 5/50 no cooling), myocardial infarction (1/50 versus 2/50 versus 2/50), and enzymes (aspartate aminotransferase myocardial band creatine kinase). No patient died. Ice topical hypothermia (versus no topical cooling) was associated with more left pleural effusions (25/50 versus 9/50; p less than 0.05), atelectasis (33/50 versus 18/50; p less than 0.05), elevated left hemidiaphragms (13/50 versus 0/50; p less than 0.05), and longer postoperative hospitalization (11.2 versus 8.5 days; p less than 0.05). Topical 4 degrees C saline reduced diaphragmatic elevation and pleural effusion (versus topical ice) but was associated with more atelectasis (34/50 versus 18/50; p less than 0.05) than no topical cooling. These data suggest that routine topical hypothermia is an unnecessary adjunct to blood cardioplegic protection in patients with coronary disease, since supplemental topical cooling does not improve postoperative hemodynamics or reduce inotropic requirements, enzyme release, or prevalence of postoperative myocardial infarction, and it increases pulmonary morbidity, which can be reduced by its avoidance. PMID- 1513153 TI - Effects of oxygenated cardioplegic solutions on myocardial aerobic metabolism. AB - Oxygenated cardioplegic solutions can deliver sufficient oxygen to support aerobic metabolism of heart tissue during cardiac arrest, but little is known about oxygen use after cardioplegic solution infusion. Exhaustion of myocardial oxygen stores after infusion of oxygenated crystalloid cardioplegic solution or Krebs-Henseleit buffer was measured in rat hearts. Since nicotinamide adenine dinucleotide accumulates when mitochondria become anaerobic, the epicardium was monitored during perfusion and ischemia. As ischemia progressed, nicotinamide adenine dinucleotide fluorescence increased, indicating exhaustion of oxygen. After buffer perfusion, at 37 degrees C, 50% of peak fluorescence was seen at 13 +/- 1 seconds and 90% at 37 +/- 3 seconds. Oxygenated cardioplegic solution increased these intervals to 57 +/- 6 and 114 +/- 9 seconds, respectively. Oxygenated cardioplegic solution at 10 degrees C increased the time to 50% fluorescence to 238 +/- 12 seconds and to 90% to 320 +/- 14 seconds. Differences between buffer and cardioplegic solution were less at 10 degrees C. Aerobic metabolism was completely abolished 6 minutes after infusion of 10 degrees C oxygenated cardioplegic solution. Maintenance of continuous aerobic metabolism during surgical cardiac arrest would require frequent administration of oxygenated crystalloid cardioplegic solution. PMID- 1513155 TI - Pulmonary hamartoma. AB - Eighty-nine cases of pulmonary hamartoma were studied. There were 51 men and 38 women, with a mean age of 57.5 years (range 14 to 76 years). A histologic diagnosis from examination of the resection specimens was obtained in all patients who had operations. Moreover, transthoracic needle aspiration biopsies were performed in 40 patients, with a diagnostic result in 34 (85%). The hamartomas were equally distributed in the pulmonary lobes; mean transverse diameter at the time of diagnosis was 21.7 +/- 16.2 mm. Tumor size was independent of the anatomic localization, but it correlated with the age of the patients (p less than 0.01). Tumor growth was recorded in 15 of 31 patients who had follow-up (45%); mean expansion in transverse diameter was 3.2 +/- 2.6 mm per year during an average observation time of 4.1 years (range 1 to 20 years). Pulmonary symptoms were present in 35 patients (39%). Seventy-five patients underwent operations as follows: enucleation (54), resection (11), lobectomy (5), pneumonectomy (4), and bronchoscopic removal (1). Since most pulmonary hamartomas are nonexpanding or slowly growing neoplasms, it is concluded that operation is necessary only when expansion is recorded in young or middle-aged patients and in patients with pulmonary symptoms. PMID- 1513154 TI - Transesophageal echocardiographic evaluation of aortic valve integrity with antegrade crystalloid cardioplegic solution used as an imaging agent. AB - Forceful intravascular injection of crystalloid causes microbubble (cavitation) formation. The resulting ultrasound-opaque medium is widely used in echocardiography as a source of contrast. The following study was performed to determine the feasibility of using antegrade crystalloid cardioplegic solution as a transesophageal two-dimensional echocardiographic imaging agent to evaluate aortic valve integrity. In patients with preexisting aortic regurgitation (n = 12), cardioplegic solution administration (driving pressure 150 to 200 mm Hg) was associated with the appearance of intracardiac cavitations in 12 of 12 patients. Among patients without preexisting valve dysfunction (n = 22), intracardiac cavitations were manifested in 20 of 22, with extension of the cavitations to the left atrium in 17. Associated cardiac dimensions (left ventricular outflow tract area and left ventricular diameter) did not exceed preceding cardiopulmonary bypass values in these patients (2.0 +/- 1.6 cm2 versus 2.6 +/- 1.2 cm2 and 1.4 +/- 0.7 cm versus 1.5 +/- 0.8 cm, respectively). It was concluded that antegrade crystalloid cardioplegic solution can be used as an echocardiographic contrast agent in this context. The inability to establish a relationship between the extent of cardioplegic intracardiac penetration and left ventricular dimensional changes limits the technique, as presently employed, to qualitative analysis of valve dysfunction. PMID- 1513156 TI - Carcinoma of the superior pulmonary sulcus. Results of irradiation and radical resection. AB - Fifty-six patients with superior sulcus syndrome were evaluated at the First Surgical Department of the University of Padua between 1981 and 1990. Forty-two patients with the characteristic of Pancoast's tumor received preoperative irradiation and then en bloc resection of the tumor, chest wall, and adjacent structures. Seven lobectomies and 35 segmentectomies or wedge resections were performed. There was one early postoperative death. Median survival was 14 months, and actuarial survival was 25% at 5 years. Patients with pain relief had better 5-year survival (36.4%) than patients without pain relief (9%). We have no patients with vertebral invasion who survived more than 1 year. Of the five patients with subclavian artery invasion, only one survived more than 1 year. Of five patients with N2 disease, only one survived more than 1 year. Our results suggest that pain relief after irradiation is a good prognostic factor, whereas N2 involvement and vertebral body and great vessel invasion are ominous factors. Another ominous prognostic factor is the Claude Bernard-Horner syndrome even if it is not a contraindication to resection. PMID- 1513157 TI - Pulmonary resection for fungal infection in children undergoing bone marrow transplantation. AB - Recipients of bone marrow transplants for hematologic malignancies are at risk for a variety of infectious complications. We have reviewed our experience with six patients 2 to 15 years of age who developed significant fungal infections of the lungs before or after bone marrow transplant. No patient was known to have active fungal or bacterial infection at the time bone marrow transplant was performed. In two patients fungal infections were diagnosed before bone marrow transplant, and operations were performed to permit bone marrow transplant under optimal conditions. Four patients had pulmonary mycoses discovered after bone marrow transplant, and underwent operation 12 to 24 days following transplant. Operations consisted of lobectomy (three), multiple unilateral wedge resections (one), staged segmentectomy and contralateral wedge resection (one), and staged bilateral wedge resection (one). Survival following bone marrow transplant was achieved for 6 months and 11 months in patients undergoing lung resection before transplant, and for 24, 30, 39, and 60 days in patients undergoing lung resections after transplant. Bone marrow transplant recipients are at high risk of pulmonary mycoses, and a vigorous search for occult fungal infections should be carried out before transplant. Aggressive operative treatment of fungal infections of the lungs combined with antifungal chemotherapy before transplant may offer the best hope of extended survival. PMID- 1513158 TI - Repair of hypoplastic or interrupted aortic arch via sternotomy. AB - Herein we describe our experience with repair of interrupted aortic arch and coarctation plus hypoplastic aortic arch in 55 consecutive infants (1984 to 1990). Median age at operation was 6 days and median weight 3.1 kg. Associated severe intracardiac anomalies were the rule. All patients had significant congestive cardiac failure, and the majority required prostaglandin E1 resuscitation and inotropic support (with or without ventilation) before the operation. All operations were performed via sternotomy with core cooling and circulatory arrest. Isolated myocardial perfusion was used in 13 patients during arch repair. A complete intracardiac (biventricular) repair was performed except in patients expected to require a Fontan operation as definitive treatment. The operative mortality overall was 14.5% (confidence limits 10% to 22%). For arch repair plus biventricular intracardiac repair, the operative mortality was 9% (confidence limits 5% to 15%), and for arch repair plus palliative intracardiac repair, 40% (confidence limits 22% to 60%). The mortality in the isolated myocardial perfusion group was 0% (confidence limits 0% to 14%), which may be related to reduced myocardial ischemic time (p less than 0.05). Actuarial survival was 75% (confidence limits 65% to 83%) at 12 months, with no subsequent deaths over 1294 patient-months (mean 28 months) of follow-up. Actuarial freedom from recurrent arch obstruction was 69% (confidence limits 48% to 85%) at 46 months' follow-up. Primary repair of interrupted aortic arch and coarctation plus hypoplastic arch compares favorably with a staged approach and is recommended even when complex intracardiac anatomy is present. PMID- 1513159 TI - Risk factors for perioperative mortality in children with anomalous origin of the left coronary artery from the pulmonary artery. AB - The present study was conducted on 33 children (median age at initial cardiac catheterization 0.4 years [0.1 to 11.8]) with anomalous origin of the left coronary artery from the pulmonary artery, without associated hemodynamically significant cardiovascular anomalies, who were treated throughout a period of 18 years in our hospital. A two coronary artery circulation was reestablished in 31 of 33 children. One child died before the intended operation, and in one child the left coronary artery was ligated. There were six operative deaths, five intraoperative and one 12 hours after operation. The purpose of the study was to assess which preoperative clinical and angiographic features were associated with a higher perioperative mortality. The following preoperative factors were associated with a statistically significant higher perioperative mortality: young age at operation (p less than 0.03), left and balanced type of coronary circulation (p less than 0.01), and electrocardiographic signs of extensive acute myocardial infarction, namely, marked ST elevation (greater than or equal to 0.2 mV in at least two leads) (p less than 0.03). Left axis deviation on the electrocardiogram was associated with an extreme right dominant type of coronary circulation (p less than 0.005). The latter was also linked with adequate perfusion of the posterolateral left ventricular wall (p less than 0.005). At autopsy, severe increase of heart weight to two or three times the normal heart weight was established in six of seven children. Thus the perioperative mortality was determined primarily by the extent of myocardial ischemia. This in turn is decisively influenced by the dominant type of coronary circulation and the extent of inter-arterial collateralization. Young age, in addition, proved to be a risk factor for mortality at corrective surgery. PMID- 1513160 TI - The influence of coronary anatomy on the arterial switch operation in neonates. AB - To determine whether coronary anatomy influences the outcome of the neonatal arterial switch operation, we examined the results in all newborn infants (n = 70) with D-transposition of the great arteries who had a corrective operation at our institution between March 1987 and April 1991. The origin and distribution of coronary arteries were identified preoperatively by echocardiography, aortic root angiography, or selective coronary arteriography and intraoperatively by direct inspection. However, the arterial switch operation was performed independent of the coronary anatomy in all but two candidates for the operation. Four early deaths occurred and five surviving patients had symptoms of impaired cardiac function. No late deaths have occurred in patients followed up for 2 to 50 months. Evidence of myocardial ischemia was present in three of the four deaths and in four of the five patients with cardiovascular symptoms. Patients with commissural or intramural coronary origins between the great arteries had significantly greater cardiovascular morbidity and mortality because of coronary ischemia than patients with the most common coronary pattern. Thus coronary anatomy may influence surgical management and the postoperative course of newborn infants with transposition. PMID- 1513161 TI - Right submammarian thoracotomy in female patients with atrial septal defects and anomalous pulmonary venous connections. Comparison between the transpectoral and subpectoral approaches. AB - A right submammarian incision with anterior thoracotomy was performed in 89 female patients to repair simple and complex forms of atrial septal defects. Patients' ages ranged from 8 to 38 years (mean 21.5 years). Seventy-seven had secundum-type atrial septal defects, one had the primum type, and 11 had an associated partial anomalous pulmonary venous connection. The patients were divided into two groups: 57 patients in group A, in whom, after a breast flap was elevated, a transpectoral approach was used to enter the chest; 32 patients in group B, in whom the pectoral muscle was not divided and a subpectoral approach was used. Aortic cannulation was accomplished without difficulty in all 89 patients. There were no early or late deaths in either group. Follow-up ranged from 24 to 108 months (mean 63.7 months) and included 86 patients, who were free of symptoms. In group A, however, among 54 patients examined, the volume of the right breast and pectoral muscle was smaller than the left in four patients (7.4%), and 21 (38.8%) had persistent right periareolar numbness. In 32 patients evaluated in group B, no difference was noted in the size of the breasts, and persistent numbness was present in four patients (12.5%). In summary, atrial septal defects or anomalous pulmonary venous connections can be safely repaired through a right submammarian thoracotomy in female patients. The subpectoral approach offers better results because breast asymmetry and paresthesias are significantly less prevalent (p less than 0.01). PMID- 1513162 TI - Quantitative analysis of pulmonary vascular disease in total anomalous pulmonary venous connection in sixty infants. AB - A quantitative analysis of small pulmonary arteries, pulmonary veins, and lymphatic vessels was conducted in autopsy cases of total anomalous pulmonary venous connection. The materials were obtained from 60 cases of total anomalous pulmonary venous connection without asplenia or pulmonary stenosis, ages ranging from 2 days to 19 months at the time of death (mean age 2.2 months). Pulmonary arterial pressure had been measured in 32 of these patients before death. Twenty cases of ventricular septal defect with pulmonary hypertension and 15 normal individuals were used as the control group. The mean thickness of the media of small pulmonary arteries and veins was 12.7 and 7.6 microns, respectively, in the total anomalous pulmonary venous connection cases, both values being significantly larger than those for normal and ventricular septal defect cases. No changes in thickness with aging were found. Medial thickness in the arteries and veins was greater in the cases of pulmonary venous obstruction than in those without such obstruction. The medial thickness of small pulmonary arteries in total anomalous pulmonary venous connection cases correlated with increased pulmonary arterial pressure. When the patients with the same pulmonary arterial pressure levels were compared, the medial thickness was always greater in those who had total anomalous pulmonary venous connection than in those who had ventricular septal defect. The medial thickness of pulmonary veins was also highly correlated with increased pulmonary arterial pressure in total anomalous pulmonary venous connection. The severity of the intimal lesions was milder in those who had total anomalous pulmonary venous connection than in those who had ventricular septal defect, suggesting the protective role of the thickened pulmonary arterial media against development of intimal lesions. Intimal fibrous thickening of pulmonary veins was not seen in the cases of ventricular septal defect, but it was present in 45% of the total anomalous pulmonary venous connection cases. Lymphangiectasia was characteristically present in 62% of the total anomalous pulmonary venous connection cases. Interstitial emphysema was often a complication of lymphangiectasia, and it led to eight postoperative deaths. PMID- 1513163 TI - The influence of pulmonary artery banding on outcome after the Fontan operation. AB - Thirty-eight patients were selected from a total of 120 patients who underwent the Fontan operation between 1974 and 1988. They were classified into two groups. Group 1 consisted of 18 patients with previous pulmonary artery banding at a mean age of 7 months (2 days to 59 months), and group 2 comprised 20 patients with native pulmonary stenosis. In group 1, 10 children had tricuspid atresia (seven with normally connected and three with transposed great arteries), six had double inlet ventricle, and two had complex heart malformations. Group 2 consisted of 12 patients with tricuspid atresia and normally connected great arteries, six with double-inlet ventricle, and two with complex malformations. The following clinical and hemodynamic parameters at cardiac catheterization and cineangiocardiography were determined in both groups before the Fontan operation: age and body surface area, hemoglobin concentration and hematocrit value, atrial and pulmonary artery pressures, end-diastolic pressure of the systemic ventricle, arterial oxygen saturation, pulmonary/systemic flow ratio, end-diastolic volume, ejection fraction and mass of the systemic ventricle, cardiac index, and Nakata index. After the Fontan operation in all patients, the presence or absence of pericardial and pleural effusions, ascites, protein-losing enteropathy, and liver and kidney dysfunction was assessed and the clinical status was classified according to New York Heart Association criteria. All preoperative and postoperative parameters were tested for differences between the two groups, and they were compared with normal values. Hematocrit value was higher in group 2 than in group 1 (57.8% versus 53.1%; p less than 0.05). Ventricular mass index was increased in group 1 when compared with group 2 (125.8 gm/m2 versus 87 gm/m2; p less than 0.05). Severe pericardial effusions in the early postoperative period were significantly more frequent in group 1 and were particularly prevalent in the subgroup with long-standing pulmonary artery banding (p less than 0.01). Subaortic stenosis was observed more frequently in group 1. The remaining parameters were not statistically different between the two groups. We conclude that the significant increment in ventricular mass after pulmonary artery banding may represent a risk for unfavorable outcome after the Fontan operation, which increases with time. Therefore, long-standing pulmonary artery banding as a palliative procedure for candidates for the Fontan operation should be avoided. PMID- 1513164 TI - Repair of left ventricular aneurysm. Changes in ventricular mechanics, hemodynamics, and oxygen consumption. AB - Anteroapical left ventricular aneurysms were produced in 23 sheep by coronary arterial ligation. Plication of the aneurysm does not change stroke volume or cardiac output and does not significantly change left ventricular oxygen consumption from the preoperative value of 5.1 +/- 2.6 ml/100 gm per minute. Plication, however, does increase left ventricular end-systolic elastance from 3.2 +/- 0.9 to 4.4 +/- 1.5 mm Hg/mm (p = 0.005). In nine of these sheep the midsagittal plane of the left ventricle was imaged by means of an array of sonomicrometry crystals before and after plication of the aneurysm. Regional wall stresses at end-systole and end-diastole and changes in diastolic function were calculated for anterior and posterior ventricular walls in the border zone adjacent to the aneurysm and in more basilar myocardium remote from the infarct. Plication significantly reduced end-systolic wall stresses and systolic stress integrals in the posterior border zone and remote myocardium, but it did not significantly change anterior wall systolic stresses or stress integrals. Plication also decreased diastolic stretching of border zone myocardium. Plication of anteroapical left ventricular aneurysm produced a shorter, more spherical ventricle and removed the dyskinetic segments but altered deformation (strain) in both circumferential and longitudinal directions. The changes in ventricular wall geometry and deformation provide an explanation for the increased ventricular end-systolic elastance and unchanged stroke volume observed after aneurysm plication. PMID- 1513165 TI - Rapid endothelialization of vascular prostheses by seeding autologous venous tissue fragments. AB - A method was developed to obtain rapid endothelialization of a fabric vascular prosthesis by seeding autologous venous tissue fragments into its wall. In an animal study, complete endothelialization was observed in the entire inner surface of the prosthesis within 2 weeks after implantation. A piece of peripheral vein was minced with scissors and then stirred into saline to create a tissue suspension. This suspension was enmeshed into the wall of a highly porous fabric vascular prosthesis by repeated pressurized injections with a syringe. The prostheses (7 mm inside diameter and 5.7 cm in length), seeded with tissue fragments, were implanted into the descending thoracic aorta of 25 dogs, and they were removed from 1 hour to 2 months after implantation. Twenty-five prostheses, preclotted with fresh blood, were used as control prostheses. In the seeded graft, a thin fibrin layer covered the inner surface just after implantation, but countless numbers of endothelial cells migrated from the fragments and came up to the luminal surface like multiple "mushrooms" under the fibrin layer. Smooth muscle cells made multiple layers underneath the endothelial cell layer. The healing proceeded equally at every part. By this active migration and proliferation, the inner surface was completely healed within 2 weeks. PMID- 1513166 TI - In vitro closing behavior of the St. Jude Medical heart valve in the pulmonary position. Valve incompetence originating in the prosthesis itself. AB - We examined the in vitro closing behavior of the St. Jude Medical heart valve, simulating (1) a low-pressure system, (2) the anatomic peculiarity of the right ventricular outflow tract and the main pulmonary artery, and (3) disturbed diastolic compliance of the right ventricle. The variables in the experiment were the load impedance to the pump and the valve orientation. The results were as follows. The sequence of closure of the two semidiscs was based on the valve orientation; reduction in impedance caused the semidisc that closed last to remain open, while the other semidisc continued its open-close motion; further reduction in impedance prevented the semidisc, which continued its open-close motion, from closing completely. These results highlight the forces involved in semidisc closure and the existence of a threshold of force for completion of semidisc closure. Further, the results demonstrate that under certain circumstances the threshold cannot be exceeded via those forces. Therefore this incompetence must originate in the prosthesis itself. In this regard, we suggest an urgent need to reconsider the indications for St. Jude Medical heart valve pulmonic implantation. Finally, we advocate the necessity for an in vitro assessment of valve prostheses in a low-pressure system, to evaluate the safety of right-sided placement. PMID- 1513167 TI - Analysis of left ventricular motion after mitral valve replacement with a technique of preservation of all chordae tendineae. Comparison with conventional mitral valve replacement or mitral valve repair. AB - The postoperative regional left ventricular motion of 22 patients with a diagnosis of mitral regurgitation, and who underwent mitral valve replacement with preservation of chordae tendineae, were retrospectively analyzed by cineangiography in the early postoperative period and by multiple-gated cardiac blood pool scintigraphy in the mid-to-late postoperative period. The operation consisted of the division of the anterior leaflet into anterior and posterior segments, the shifting and reattachment of the divided segments to the mitral ring of the respective commissural areas, and the use of a low-profile bileaflet prosthetic valve. Control groups consisted of 28 patients with mitral regurgitation who underwent mitral valve replacement with a conventional technique and 16 patients who underwent mitral valve repair. Compared with the conventional mitral valve replacement group, the radial shortening of the left ventricle of the chordae-preserved mitral valve replacement group was greater at the apical septal, inferoapical, anterobasal, and anterolateral portions, whereas the radial shortening of the repair group was greater than that of the chordae preserved group only at the inferolateral portion. The ejection fraction of the whole left ventricle was statistically greater in the chordae-preserved group, and also regional ejection fraction of the chordae-preserved mitral valve replacement group was greater at the apical septal, inferoapical, inferolateral, anterobasal, and anterolateral portions than that of the conventional mitral valve replacement group at these portions. On the other hand, the postoperative regional and global motion was identical to that of the mitral valve repair group except at the inferolateral portion. The result of this study supports a concept that maintenance of continuity between the mitral anulus and the papillary muscle has a beneficial effect on postoperative left ventricular performance. PMID- 1513168 TI - The vanishing tricuspid annuloplasty. A new concept. AB - A tricuspid De Vega annuloplasty with absorbable 2-0 polydioxanone sutures was performed on 16 sheep supported by cardiopulmonary bypass. The anulus diameter was reduced by 2 to 6 mm. Four sheep died perioperatively. The 12 survivors were electively killed at 2-week intervals during a period of 6 months. Infective endocarditis was not observed. At the time of death no gradient was found on simultaneous pressure measurements of the right atrium and ventricle. Epicardial echocardiography did not reveal tricuspid stenosis or regurgitation. Macroscopically there was no thrombus and the tricuspid leaflets were of a normal appearance. A thin white cord was observed at the anulus in all animals killed after 12 weeks. The annular size remained as surgically induced until the fourth month, but it reverted to its preoperative size after 5 months. Histologically there was granulation tissue initially only around the foreign material, but then progressively it appeared also between the foreign filaments, with the development of multinucleated foreign body giant cells. At approximately 5 months most of the foreign material had been disrupted or absorbed, leaving a tenuous ring of granulation tissue, which allowed expansion of the tricuspid ring to its original circumference. By 6 months most of the foreign material had disappeared and was replaced by loose collagenous tissue. The concept of a "vanishing annuloplasty" is advanced, with particular application in children and in patients with functional tricuspid insufficiency. PMID- 1513169 TI - Wolff-Parkinson-White syndrome. A quantitative morphometric analysis of surgical anatomy. AB - Previous descriptions of the four anatomic regions of dissection in Wolff Parkinson-White syndrome have been largely qualitative. In this study quantitative data describing this anatomy are presented, together with statistical analysis of selected anatomic relationships. Fourteen human hearts were dissected. The borders of the posteroseptal dissection along the mitral anulus, tricuspid anulus, and epicardium were measured. A positive correlation between the mitral and tricuspid annular dimensions was found (r = 0.55; p = 0.04); however, the length of epicardial dissection was more variable. The dimensions of the anteroseptal space and the position of the right coronary artery within this space were measured. These measurements emphasize the proximity of the aortic sinuses of Valsalva to the right atrial endocardium near the posteromedial extent of the dissection. The dimensions of the right and left free walls and the position of the coronary arteries within these spaces were measured. A positive correlation was found between the width of the atrioventricular groove and the length of the dissection necessary to separate the atrioventricular groove fat from the ventricular surface (r = 0.89; p = 0.0001, right free wall; r = 0.87; p = 0.0001, left free wall). The quantitative data presented in this article are intended to enhance the surgeon's appreciation of the anatomy relevant to the treatment of Wolff-Parkinson-White syndrome. The knowledge gained from this quantitative analysis may improve accuracy in the electrophysiologic localization and surgical disruption of accessory atrioventricular connections. PMID- 1513170 TI - Permanent pacing following cardiac transplantation. AB - Permanent pacemakers were inserted in 20 of 439 patients who had received 453 orthotopic cardiac allografts since 1980 at the Columbia-Presbyterian Medical Center. Mean age at transplantation was 45 +/- 4 (SEM) years (range 10 to 64). Pacemakers were inserted an average of 2.4 +/- 1 months after transplantation (range 0.4 to 29), 16 of 20 (80%) within the first month. Indications included sinus bradycardia or sinus arrest in 15 (75%), third-degree heart block in 2 (10%), and both sinus node and atrioventricular node dysfunction in 3 (15%). Rejection episodes and pacemaker insertion were associated in 8 patients (40%). Pacing modes included DDD (7 patients, 35%), AAI,R (7 patients, 35%), VVI,R (3 patients, 15%), DDD,R (2 patients, 10%), and VVI (1 patient, 5%). There was no pacing-related morbidity or mortality. Fourteen of 20 patients (70%) are alive and well 3 to 48 months (mean 24 +/- 4) after transplantation. Late follow-up indicated that atrioventricular node dysfunction resolved in one of two patients, sinoatrial node dysfunction improved or resolved in 7/13 patients, and no atrioventricular block developed in 11 (8 to 37 months, mean 22 +/- 3). Permanent pacing can be safely performed following orthotopic cardiac transplantation, predominantly for sinus node dysfunction. The requirement for pacing may reflect ongoing or new onset rejection and patients should therefore be evaluated accordingly. Dual-chamber pacing is probably not necessary unless atrioventricular node dysfunction is coexistent. Further, as most transplant recipients return to an active life-style, AAI,R may be the preferred mode of pacing. PMID- 1513171 TI - Improved recovery of heart transplants by combined use of oxygen-derived free radical scavengers and energy enhancement. AB - Oxygen free radical injury during reperfusion of ischemically stored heart transplants may further impair the ability of the transplanted heart to reuse substrate for recovery. We compared the effects of oxygen free radical scavengers, superoxide dismutase and catalase, either alone or combined with glucose-insulin-potassium, in an improved model of the heterotopically transplanted rat heart. Group 1 hearts (n = 8) received no preservation before transplantation and were transplanted immediately. Hearts in four other groups (n = 8 for each group) underwent cold storage (4 degrees to 6 degrees C) for 3 1/2 hours before transplantation. Five minutes before reperfusion of the transplanted hearts, recipient rats received one of the following intravenous treatments: saline (group 2), glucose-insulin-potassium (group 3), superoxide dismutase/catalase (group 4), and superoxide dismutase/catalase plus glucose insulin-potassium (group 5). Left ventricular end-diastolic pressure, rate of rise of left ventricular pressure, myocardial blood flow, coronary resistance, and tissue adenosine triphosphate content of the heart transplants were assessed during or at the end of 2 hours of reperfusion. Hearts treated with superoxide dismutase/catalase alone showed improvement of end-diastolic pressure and myocardial blood flow. The use of glucose-insulin-potassium alone did not facilitate the recovery of transplanted hearts. In contrast, the combined use of superoxide dismutase/catalase plus glucose-insulin-potassium resulted in a superior recovery of all functional and hemodynamic parameters. These results indicate that free radical scavengers in the presence of glucose-insulin potassium significantly improve functional recovery in the setting of heart transplantation. PMID- 1513172 TI - Temperatures attained by donor hearts stored in ice during transport are not too cold. PMID- 1513173 TI - Experimental retinal pneumoembolism. PMID- 1513174 TI - Reconstruction of the right ventricular outflow tract in truncus arteriosus types I and II with a pulmonary homograft. PMID- 1513175 TI - Pulmonary homograft replacement for primary leiomyosarcoma of the pulmonary artery. PMID- 1513176 TI - Constrictive pericarditis developing forty-five years after gunshot wound. PMID- 1513177 TI - Postprandial flow physiology of the gastroepiploic artery graft. PMID- 1513178 TI - Marked enlargement of the right pulmonary artery nineteen years after Waterston operation. PMID- 1513179 TI - A personal computer-based spike detector and sorter: implementation and evaluation. AB - Many studies of neuronal activity require isolation of the extracellular wave form (spike) of a single neuron from the potentials generated by nearby cells. A variety of methods for spike sorting exists, but most are expensive and require specialized hardware and software. Moreover, there is no easy and objective way for evaluating and comparing the performance of spike sorting devices. We describe here a system for on-line spike sorting that is implemented on an IBM PC/AT computer using commercially available hardware and C-language software. Spikes are detected after crossing an amplitude threshold and are sorted or rejected by template matching. The templates are constructed in a learning phase, using a fast manual sorting of all detected spikes. Later, each detected spike is matched against all defined templates. A detected spike which does not match any template, or matches more than one, is rejected. A continuous display of the wave forms of the last 256 sorted, double-matched, and rejected spikes is used as the main tool for parameter adjustment and error detection. Also described is a new and highly versatile tool for generating appropriate wave forms for critical evaluation of sorter performance. Using the same hardware and software tools, a simulation program mimics the extra-cellular activity of several neurons by linear combination of two vectors and added random noise. The size, shape and the variability of the action potential, as well as its firing pattern, can be adjusted. Comparison of the sorter output with the known simulated activity is used to examine the sorter performance and limitations. PMID- 1513180 TI - An immunocytochemical method for marking microelectrode tracks following single unit recordings in long surviving, awake monkeys. AB - We describe an immunocytochemical method for marking microelectrode tracks made during single-unit recordings in long surviving, awake monkeys. This procedure detects the increase in glial fibrillary acidic protein in the glial cells along a microelectrode track using commercially available antibodies. We have successfully marked electrode tracks in tissue from preparations having postrecording survival times ranging into months even though the gliosis can no longer be detected with conventional stains for cell bodies. When this method is combined with data from electrophysiological recordings in chronic preparations it will be possible to reconstruct functional architecture using chronic preparations, as has been done previously with acute preparations. PMID- 1513181 TI - Kinetics of diffusion in a spherical cell. I. No solute buffering. AB - Realistic neuron models that involve effects of concentration changes of second messengers on ion channels must include processes such as diffusion and solute buffering. These processes, which span a wide range of spatial and temporal scales, may impose a severe computational burden. In this paper and its companion, we examine the kinetics of diffusion and present methods for stimulating it accurately and efficiency. The problem of calcium diffusion in a spherical cell is used as a device to demonstrate the practical application of our analysis. However, the scope of these papers is not limited to this problem. The same analysis that we apply and concerns that we raise are germane to the spread of any second messenger, and can be adapted to other geometries. The focus of this paper is the simplest case: diffusion in the absence of solute buffering. This analysis also applies whenever buffering is so fast that it is instantaneous compared to diffusion, or so slow that concentration gradients have dissipated before substantial buffering takes place. The second paper investigates the more difficult situation where diffusion and buffering occur at comparable rates. In the absence of buffering, concentration changes produced by diffusion can be fit by an infinite series of exponential terms. We show how to design a model with N + 1 compartments that fits the N slowest terms of this series exactly in a shell just inside the cell membrane. PMID- 1513182 TI - Epi-polarization and incident light microscopy readily resolve an autoradiographic or heavy metal label from an obscuring background or second label. AB - Difficulty encountered in resolving grains of exposed photographic emulsion in autoradiographs of the densely melanized retinal pigment epithelium was solved by using epi-polarized or incident light microscopy. The apparatus used included a metallurgical illuminator specifically designed for epi-polarization microscopy or, as a less expensive but only slightly less effective alternative, a modified fluorescence illuminator. The black melanin granules absorb incident light (as they do in vivo) while the silver grains reflect it producing a "darkfield-like" representation. Brightfield and darkfield-like images can be alternated easily and quickly, or both can be viewed simultaneously. Epi-polarization microscopy has wider application in resolving a reflective label over any opaque background staining or dark second label. PMID- 1513183 TI - Flattening the cerebral cortex by computer. AB - A computer program was developed for unfolding the cerebral cortex so that it could be viewed as a 2-dimensional surface. Input to the program consisted of tissue sections cut in a standard plane of section. Each section was represented by one line, which corresponded to a contour line in the flattened map. From these data, the computer constructed a 3-dimensional surface representation, which it then flattened. Because the cerebral cortex has considerable intrinsic curvature, flattening required that some regions be expanded and others shrunken. These changes occurred as a natural consequence of local decisions made by the computer as it laid down successive contours. The user could intervene during both surfacing and flattening in order to shape the developing map. The program has been used to generate 37 flattened maps from various regions of cat cortex, and 1 from monkey cortex. The local topography of cortical features such as gyri, sulci, architectonic boundaries, and patches of transported tracer, appeared to be conserved fairly faithfully. Areal distortion was also modest, with an average change in surface area of only 12%. PMID- 1513185 TI - Kala-azar: current status of experimental chemotherapy. PMID- 1513186 TI - Pharmacological basis of the therapeutic effect of (-)deprenyl in age-related neurological diseases. AB - (-)Deprenyl (Selegiline, Jumex, Eldepryl, Movergan), a close structural relative to phenylethylamine (PEA), is a drug of a unique pharmacological spectrum. (a) It is highly potent and selective irreversible inhibitor of B-type monoamine oxidase (MAO), a predominantly glial enzyme in the brain, the activity of which significantly increases with age. (-)Deprenyl was the first selective inhibitor of MAO-B described in literature, became the worldwide research tool used for blocking selectively B-type MAO, and is still the only MAO-B inhibitor in clinical use. (b) (-)Deprenyl interferes with the uptake of catecholamines and indirectly acting sympathomimetics because it is handled by the catecholaminergic neuron similarly to the physiological substances transported through the axonal end-organ and vesicular membrane. The unique behavior of (-)deprenyl is that, in striking contrast to PEA and its relatives, it does not push the transmitter from the storage places, i.e., it is not a releaser. The net result is that ( )deprenyl inhibits the releasing effect of tyramine and is presently the only safe MAO inhibitor which can be administered without dietary restrictions. (c) Maintenance on (-)deprenyl enhances selectively superoxide dismutase (SOD) and catalase activity in the striatum. This effect is unrelated to the MAO and uptake inhibitory effects of the drug. (d) Maintenance on (-)deprenyl facilitates the activity of the nigrostriatal dopaminergic neurons with remarkable selectivity. This effect is also unrelated to either the MAO or the uptake inhibitory effects of the drug. All in all, (-)deprenyl maintains the activity of the nigrostriatal dopaminergic machinery on a higher activity level and slows down its age-related decline. Male rats maintained on (-)deprenyl lost their capacity to ejaculate later, retained their learning ability longer, and lived longer than their saline treated peers. Parkinsonians on levodopa plus (-)deprenyl (10 mg daily) lived significantly longer than those on levodopa alone. (-)Deprenyl is the first drug which retards the progress of Parkinson's disease. Freshly diagnosed parkinsonians maintained on (-)deprenyl did not require levodopa until significantly later than their placebo-treated peers. Maintenance on (-)deprenyl significantly improved the performance of patients with Alzheimer's disease. It is concluded that in Parkinson's disease and Alzheimer's disease patients need to be treated daily with 10 mg (-)deprenyl from diagnosis until death, irrespective of other medication.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1513187 TI - Opioid agonists and antagonists: an evaluation of their peripheral actions in inflammation. PMID- 1513184 TI - Adenosine A1 and A2 receptors: structure--function relationships. PMID- 1513188 TI - Influence of buffered and unbuffered acetylsalicylic acid on dental enamel and dentine in human teeth: an in vitro pilot study. AB - An in vitro study was conducted to investigate the erosive effect of buffered and unbuffered acetylsalicylic acid (ASA) on dental enamel and dentine in human teeth by scanning electron microscopy. In order to standardize the specimens and to improve comparability the dental enamel and dentine were superficially abraded. The enamel and dentine specimens were therefore particularly sensitive to the influences of acid agents. Concentrated solution of buffered chewable ASA tablets (500 mg ASA and 300 mg calcium carbonate in 5 ml water) showed no changes in the enamel surface structure after exposure times of 1 min, 5 min and 60 min. In contrast, minimal corrosive effects were already seen after exposure of the enamel surface to the unbuffered ASA solutions for 1 min. After exposure times of 5 min and 60 min erosion of the enamel was more pronounced. Immersion in the unbuffered ASA solution led to clearly visible micromorphological changes on the dentine surfaces even after exposure for 1 min. Exposure of the dentine specimens to the buffered ASA solutions led to only very slight changes in the surface morphology. Therefore, the scanning electron micrograph after exposure to buffered ASA is comparable to the picture of untreated dentine. PMID- 1513189 TI - Induction and termination of afterdepolarizations and triggered arrhythmias by drugs in cat heart in vivo. AB - In order to investigate some anti-triggered arrhythmic drugs, the afterdepolarizations and triggered arrhythmias were induced by cesium chloride and the monophasic action potentials of the left ventricular epicardium in vivo were recorded by using a contact electrode in 58 cats. These results suggested that a) early- and afterdepolarizations, oscillatory afterpotentials and some different kinds of triggered arrhythmias were induced by cesium chloride, b) sodium valproate (150 mg/kg) could prevent CsCl-induced triggered activities, c) lidocaine (5 mg/kg), ethmozine (5 mg/kg) and sodium valproate (150 mg/kg) could terminate CsCl-induced ventricular tachycardias. The present studies provide a basically experimental evidence for treating triggered arrhythmias in clinic. PMID- 1513190 TI - Interactions between digitoxin and some antiarrhythmic drugs. AB - In the present study the pharmacokinetic interactions between digitoxin and the antiarrhythmic drugs amiodarone, mexiletine and propafenone have been examined. Experiments were performed on rabbits in which serum digitoxin concentration was used as indicator to detect drug interactions. The radioimmunoassay "Coat-A Count" procedure of DPC was used for the quantitative measurement of digitoxin. It was determined that in order to achieve a considerable level of serum digitoxin, it was necessary to administer a multiple dose rather than the one tolerated by humans. It was also observed that serum contained digitalis like immunoreactive factor(s) (DLIF) measured as digitoxin. The mean (+/- SE) digitoxin equivalent value of the DLIF, measured by the "Coat-A-Count" radioimmunoassay in the serum of rabbits (n = 34) was 4.15 +/- 0.059 ng/ml. Each of the three antiarrhythmic drugs increased serum digitoxin levels; its values were almost double in relation to the control group where only digitoxin was administered. This increased digitoxin value was detected one hour after administration of the first dose of the antiarrhythmic drug and remained at a higher level than that of the control group for 6-8 hours. Rabbits given a single high dose of digitoxin and some of the antiarrhythmic drugs and those given a small dose of digitoxin for only four days, presented a retrogressive increase of digitoxin level in serum 5-6 days later. This mechanism needs to be further investigated. PMID- 1513191 TI - Enhancement of systemic delivery of met-enkephalin and leu-enkephalin eyedrops with permeation enhancers. AB - It was found that methionine enkephalin (Met-Enk) and leucine-enkephalin (Leu Enk) can be delivered efficiently into the systemic circulation through the outer route in rabbits. When 50 mcl of 1% Met-Enk eyedrops without absorption enhancers were instilled into eyes, the rabbits' blood concentration rose from 92 pg/ml to 153 pg/ml in 10 min. When either of two permeation enhancers (BL-9 or Brij-78) was added at a 0.5% concentration to the ophthalmic solution, the systemic absorption of 1% Met-Enk was markedly improved. Its blood level was increased to approximately 3.4 times that without the enhancer. When the eyedrops of 0.3% Met Enk plus 0.5% absorption enhancer were administered, the blood concentration reached higher than that reached by 1% Met-Enk without permeation enhancers. Similar results were obtained with Leu-Enk except the systemic absorption was enhanced by BL-9 and Brij-78 even further to 10-fold and 8.3-fold, respectively. These results indicate that the systemic delivery of Met-Enk and Leu-Enk through eyes, especially with the addition of permeation enhancers, is a feasible alternative route to parenteral injection. PMID- 1513192 TI - Absorption of various erythromycin esters and salts in mice after intragastric intubation. AB - Erythromycin base and its different salts and esters were given intragastrically to mice. Serum concentrations of erythromycin and its 2'-esters were determined by the bacterial growth inhibition method. Acetyl and propionyl erythromycin were the best absorbed 2'-esters, and differed significantly from butyryl erythromycin and erythromycin base. Erythromycin estolate yielded a larger area under the concentration curve than acistrate or stearate. Among the syrup preparations, erythromycin acistrate was significantly better absorbed than 2'-ethylsuccinyl erythromycin. Absorption of 2'-esters decreased with increasing number of esterified carbon atoms and increasing hydrophobicity and increasing log P value (the logarithm of octanol-water partition coefficient). In addition to sufficient lipophilicity, the optimum absorption of erythromycin esters seems to require a high hydrophilicity. PMID- 1513193 TI - Pharmacokinetics and bioavailability of papaverine HCl after intravenous, intracorporeal and penis topical administration in beagle dogs. AB - Bioavailability and pharmacokinetics of papaverine HCl was studied in beagle dogs following intravenous injection, intracorporeal injection and topically applied gel on the penis. Also the effect of the sorption promoter Labrafil M-1944 CS on the permeation of papaverine from two gel formulations (PT and PTL) containing the co-solvent Transcutol was evaluated. Blood samples were analyzed by high performance liquid chromatography (HPLC). The pharmacokinetic parameters were determined using either curve-fitting (RE-SID) or compartment model independent method (AUC-RPP). The plasma concentration-time profiles show that papaverine HCl pharmacokinetics is best described by an open two-compartment model. The absolute bioavailability of papaverine HCl was determined to be 102.4%, 9.1%, and 12.4%, respectively, following intracorporeal injection, gel PT and gel PTL administration. PMID- 1513194 TI - Influence of cisapride, metoclopramide and loperamide on gastric emptying of normal volunteers as measured by means of the area under the curve of the cumulative fraction absorbed-time profiles of paracetamol. AB - The present study with paracetamol was designed to compare the effects of 40 mg cisapride, 20 mg metoclopramide and 4 mg loperamide given orally on gastric emptying under fasting conditions in normal volunteers. The well known bioavailability parameters of absorption and the area under the curve of the fractional absorbed time profiles up to 30 min were used as an index of gastric emptying. As reflected by the AUC of the fractional absorbed time profiles, it was concluded that pretreatment with cisapride speeded up the gastric emptying under fasting conditions. Tmax was the only normal bioavailability parameter that showed any significant change after cisapride treatment. Pretreatment with therapeutic doses of loperamide and metoclopramide did not significantly modify stomach emptying. PMID- 1513195 TI - Hypotensive anesthesia for middle ear surgery: a comparison of propofol infusion and isoflurane. AB - An infusion of propofol (2,6-diisopropylphenol) was compared with isoflurane to induce hypotension for middle ear surgery. Forty patients (ASA physical status I II, 16-55 years) scheduled for elective surgery were included in an open randomized study. The pharmacokinetics of propofol infusion were also studied in 6 patients. Both agents produced controlled hypotension (MAP reduction of 30% from the baseline values) with an acceptable visibility of the surgical field. No major complications occurred. The mean total dose of propofol infusion was 6.4 +/ 2.7 mg/kg and the mean concentration of isoflurane was 0.9 +/- 0.4%. Considerable interindividual pharmacokinetic variability was found and propofol was extensively distributed and rapidly cleared from the body after the infusion. Propofol infusion may be a new alternative as a hypotensive agent in middle ear surgery. PMID- 1513196 TI - Pain sensitivity range: a useful parameter to measure experimentally induced pain? AB - Although the Pain Sensitivity Range (PSR) has been presented as a useful parameter to measure pain in the laboratory, it has not received much attention from pain researchers. The goals of the present investigation were to analyze the reliability and stability of the PSR with the cold pressor test method. Results of our study indicate that useful data can be obtained from this parameter. The PSR is a reliable measure which has not shown any variability due to the cyclic changes in pain perception nor due to the supposedly greater pain sensitivity on the left side of the body. The authors postulate that PSR might be a good measure in laboratory research to evaluate the effectiveness of analgesic therapies, for its resemblance to the acute pain experience. PMID- 1513197 TI - Digoxin therapeutics: straightening out the facts. AB - This article is essentially a review of the pharmacokinetic rationale behind digoxin therapeutics. It covers the various approaches to digoxin therapeutics including the therapeutic endpoint and the use of plasma concentrations of digoxin, the various problems involved in dosage design (particularly pharmacokinetic variability), prescribing aids (and their total impact on the variability in plasma concentrations achieved), and finally, the alternative use of blood-level data to separate and identify the variation in absorption disposition from the variation in the relationship of plasma concentration to effect. On the basis of available data, it is concluded that by both turning to prescribing aids that have been formulated from clinical data gathered under more nearly ideal conditions and selecting the dosage to give a target concentration based on single measurements of serum digoxin concentrations, may not result in much improvement over fixed or intuitive dosing as far as achieving a predetermined target level is concerned. The probable causes for this lack of precision are explored, and finally an optimum approach to digoxin therapeutics is defined. PMID- 1513198 TI - Influences of roxithromycin on cell-mediated immune responses. AB - We investigated the effects of roxithromycin (RXM), a synthesized macrolide antibiotic on murine cellular immune responses by examining the in vitro proliferative response of lymphocytes, interleukin 1 (IL-1) production and interleukin 2 (IL-2) production. RXM was orally administered to BALB/c mice at a dose of 5 mg/kg once a day for 42 days. Spontaneous blastic activity of lymphocytes prepared from mice administered with RXM for 7 days was higher than those from control mice. The activity peaked at the 14th day, and then decreased gradually to control levels by the 42nd day. Time kinetics of lymphocyte blastogenesis to concanavalin A showed a pattern similar to that observed in spontaneous blastic activity. Oral administration of RXM also influenced cytokine production; short-term (for 14 days) administration of RXM enhanced both IL-1 and IL-2 production but long-term (for 42 days) administration inhibited them. PMID- 1513200 TI - Aldose reductase mRNA expression and its activity are induced by glucose in fetal rat aortic smooth muscle (A10) cells. AB - The induction of aldose reductase (AR) mRNA expression and its activity by glucose were investigated in fetal rat aortic smooth muscle (A10) cells. The increase in the expression of AR mRNA was observed at 6 h, and reached a maximum (2.3 fold) at 12 h after exposure to 80 mM glucose. On the other hand, increase in AR activity was observed at 12 h and reached a maximum (2 fold) at 48 h after exposure to 80 mM glucose. AR mRNA levels as well as its activity increased almost linearly in a concentration dependent manner up to 80 mM. Although not significant, there was a consistent increase in AR mRNA level and its activity at 23.75 mM glucose. There was a good correlation between AR mRNA level and AR activity. In the presence of 1 microgram/ml actinomycin D, the increase in the expression of AR mRNA level by glucose was almost completely abolished, suggesting its transcriptional regulation by glucose. Other osmolytes were also effective in inducing AR mRNA expression as well as its activity at 80 mOsm/kg. Therefore, the increase in AR mRNA level and its activity by glucose in A10 cells may be a response to the increase in osmolarity. PMID- 1513199 TI - Effect of nifedipine and S-adenosylmethionine in the liver of rats treated with CCl4 and ethanol for one month. AB - An experimental model of toxic liver injury in rats was employed to assay the effect of Nifedipine (a calcium antagonist blocker) and S-Adenosylmethionine (a precursor of glutathione). An important decrease in both perivenular fibrosis and cirrhosis was found. Furthermore, a significant decrease in lactic acid levels was found in the group of animals treated with pharmacologic therapy, although no correlation was seen between lactic acid levels and the different degrees of perivenular fibrosis. No significant variations in ALT and AST enzymes were observed between both groups, as opposed to a significant decrease in LDH enzyme in the Nifedipine+S-Adenosylmethionine group. The results indicate an improvement in the histologic picture of the liver in rats treated by means of pharmacological association, without any change in inflammatory infiltrate and with a slight decrease in necrosis, indicating an action mechanism via creeping fibrosis (instead of a hepatitis pathway). PMID- 1513201 TI - The hypertriglyceridemic rat as a genetic model of hypertension and diabetes. AB - Hypertriglyceridemia was demonstrated in untreated hypertensive patients as well as in animals with genetic and experimental hypertension. The main purpose of the present study was to evaluate the possibility to use the hereditary hypertriglyceridemic (HTG) nonobese rats in hypertensive research. Direct measurement of blood pressure demonstrated significantly higher systolic, diastolic and mean arterial pressures in HTG rats in comparison with control Wistar rats. There was significant positive correlation between blood pressure and plasma triglyceride concentration (r = 0.585, n = 40, p less than 0.001). In addition, there were significantly increased plasma norepinephrine and epinephrine concentrations in HTG rats, suggesting that the stimulation of sympathetic nervous system could be one of the pathogenetic mechanisms involved in the increase of blood pressure of HTG rats. PMID- 1513202 TI - Evidence that histamine-stimulated prolactin secretion is not mediated by an inhibition of tuberoinfundibular dopaminergic neurons. AB - The effects of histamine on prolactin secretion and the activity of tuberoinfundibular dopaminergic (DA) neurons were examined in male rats. Tuberoinfundibular DA neuronal activity was estimated in situ by measuring the metabolism [concentration of 3,4-dihydroxyphenylacetic acid (DOPAC)] and synthesis [accumulation of 3,4-dihydroxyphenylalanine (DOPA) after administration of a decarboxylase inhibitor] of dopamine in the median eminence. Intracerebroventricular (icv) injection of histamine produced a dose- and time dependent increase in plasma prolactin levels but had no effect on DOPA accumulation or DOPAC concentrations in the median eminence. These results indicate that the stimulation of prolactin secretion following icv histamine is not mediated by an inhibition of tuberoinfundibular DA neurons. PMID- 1513203 TI - Repeated administration of triiodothyronine enhances the susceptibility of rats to isoniazid- and picrotoxin-induced seizures. AB - In an experimental condition of hyperthyroidism, obtained by repeated administration of triiodothyronine in adult rats (100 micrograms/kg/day, sc for 7 consecutive days), there is an increased susceptibility to the convulsant effect of isoniazid (300 mg/kg, ip) and picrotoxin (4 mg/kg, ip). On the other hand, the characteristics of brain [3H] flunitrazepam binding sites are not modified. These data afford further experimental evidence of the influence of thyroid hormones on brain function. PMID- 1513204 TI - Down regulation of masked and unmasked insulin receptors in the liver of transgenic mice expressing bovine growth hormone gene. AB - The interaction of insulin with its receptor was studied in microsomes from livers of transgenic mice expressing the bovine growth hormone gene with mouse metallothionein-1 promoter (MT/bGH) and in their normal (non-transgenic) littermates. Specific binding of 125I-insulin was detected in hepatic microsomes from normal and transgenic mice with an apparent Kd of 8 and 200 nM, for high and low affinity sites, respectively. The transgenic MT/bGH mice had a marked hyperinsulinism without significant elevation of plasma glucose levels. Under identical conditions of preparation and incubation, microsomes from the transgenic male and female mice bound 39% and 34% less insulin than those from their litter mates. Scatchard's analysis indicates that this decrease in binding is due to a decrease in the number of receptor sites. In contrast to the marked decrease in insulin binding to unmasked receptors, the levels of masked (also called cryptic) insulin receptors were similar (or slightly increased) in transgenic mice microsomes as compared to those of their normal litter mates. PMID- 1513205 TI - The comparative effects of propofol, thiopental, and diazepam, administered intravenously, on pentylenetetrazol seizure threshold in the rabbit. AB - The anticonvulsant effects of propofol, thiopental, and diazepam, administered intravenously, on pentylenetetrazol (PTZ) seizure threshold were studied and compared in the rabbit. The PTZ seizure threshold determined in various rabbit groups during the control phase of conducted experiments, was found to be in the range of 10.1 +/- 2.0 to 13.5 +/- 3.7 mg/kg. Intravenous administration of comparable doses of propofol, thiopental, and diazepam resulted in marked and significant increases in PTZ seizure threshold. At all administered doses (1.25 10.0 mg/kg), propofol was found to be more effective than thiopental in increasing the PTZ threshold dose. However, the anticonvulsant effects of diazepam were more marked than those of propofol, except at a dose of 10 mg/kg where both agents exhibited equipotent activities. These data demonstrate that propofol enjoys a considerable degree of anticonvulsant activity in the rabbit. This anticonvulsant action is greater than that of thiopental at doses ranging from 2.5 to 10 mg/kg and equipotent with diazepam at the 10 mg/kg dose. PMID- 1513206 TI - Methods for medical decision making. PMID- 1513207 TI - Stochastic trees: a new technique for temporal medical decision modeling. AB - This paper introduces stochastic trees, a new modeling approach for the class of medical decision problems in which risks of mortality and morbidity may extend over time. A stochastic tree may be regarded as a continuous-time version of a Markov-cycle tree, or alternately, as a multi-state DEALE model. Optimal decisions in stochastic trees can be determined by rollback, much in the same fashion as decision trees. The author discusses how age-dependent mortality rates and declining incidence rates may be modeled using stochastic trees. Concepts are illustrated using examples from the medical literature. It is argued that stochastic trees possess important advantages over Markov-cycle trees for medical decision modeling. PMID- 1513208 TI - Comparing and optimizing diagnostic tests: an information-theoretical approach. AB - An ideal method for assessing performance of non-binary diagnostic tests would specify each test's optimal operating point and would tell a diagnostician which of many tests was the best one to use in a particular clinical situation. This article shows how information theory and receiver operating characteristic (ROC) analysis can be combined to evaluate and compare diagnostic tests at their optimum cutoffs once disease prevalence and test properties are specified. Though it is not appropriate for all clinical situations, the method can be used for most diagnostic tests whenever information is desired for its own sake or when reducing uncertainty is the goal of testing. The method also is appropriate in those situations where benefits and costs cannot be specified precisely enough to permit test optimization based on a balancing of anticipated goods and evils. PMID- 1513209 TI - Measuring decision sensitivity: a combined Monte Carlo-logistic regression approach. AB - Modeling of the uncertainty of multiple input variables for a complex decision problem complicates sensitivity analysis. A method of analysis comprising stochastic simulation of the model and logistic regression of the simulated dichotomous decision variable against all of the input variables yields a direct measure of the importance of input variables to the decision. This method is demonstrated on a previously analyzed clinical decision either to continue observation or to immediately treat with anticoagulants a woman presenting with deep vein thrombosis in the first trimester of pregnancy. A relative measure of the importance of each input variable in causing a change of decision is estimated by calculating the change in the log odds attributable to variation of each input variable over its range of uncertain values compared with the total change of log odds from variation of all input variables. This method is compared with alternative measures of input variable importance, and is found to be a simple yet powerful tool for gaining quantitative insight into the nuances of a decision model. PMID- 1513210 TI - Clinical assessment of the probability of coronary artery disease: judgmental bias from personal knowledge. AB - Probability estimates of angiographic coronary artery disease made by experienced, board-certified staff cardiologists were compared with those of cardiologists in training (fellows). In addition, estimates made before coronary angiography were compared with those made several months later based on written clinical summaries of 15 items of objective clinical and test data. Cardiologists were asked to estimate the probabilities of coronary artery disease, multivessel disease, and triple-vessel or left main disease. The study population consisted of 510 consecutive patients without valvular disease referred for the first time for coronary angiography to three hospitals. Both staff and fellows consistently overestimated the pre-angiographic probability of coronary artery disease. The probabilities estimated from patient summaries were always significantly lower than the pre-angiographic assessments. Only staff cardiologists reliably assessed the probabilities of coronary artery disease during the second assessment (p less than 0.05). Thus, estimates of disease probability based on clinical judgment vary according to the source of information, and these estimates are more accurate when physicians have objective data on hand and do not know the identities of the patients. PMID- 1513211 TI - A method to describe physician decision thresholds and its application in examining the diagnosis of coronary artery disease based on exercise treadmill testing. AB - The authors developed a method that utilizes logistic regression analysis to 1) calculate the disease probability with confidence intervals at which any specified proportion of physicians reaches a clinical decision, 2) statistically test whether factors other than disease probability affect this clinical decision, and 3) statistically test whether physician decision making in relation to disease probability varies by other factors. They apply the method to analyze the relationship between disease probability and the proportion of physicians who diagnosed coronary artery disease (CAD) in 127 consecutive subjects who completed the treadmill exercise tolerance test (ETT) at two hospitals. Twenty-five percent of the physicians decided that CAD was possible or definite at a post-ETT disease probability of 0.24 (95% CL= 0.07-0.35); 50% at 0.54 (95% CL = 0.43-0.70); and 75% at 0.82 (95% CL = 0.67-1.0). Multivariate logistic regression analysis revealed three factors significantly and independently related to the diagnosis of CAD: post-ETT disease probability, positive ETT result, and cigarette smoking. The proportion of physicians who reached a diagnosis of CAD did not differ by hospital setting (VA versus university), level of training (attending versus housestaff/fellow), or diagnosing service (cardiology versus other internal medicine). It is concluded that factors other than disease probability may affect physician diagnostic decisions. PMID- 1513212 TI - Comparing methods of learning clinical prediction from case simulations. AB - Feedback to physicians about how they use information in making judgments can improve the quality of their judgments, but questions remain about which types of feedback are most effective. The authors conducted a controlled study of feedback in 60 medical students learning to predict the risk of cardiovascular death based on the presence or absence of five risk factors. After a pretest of 40 cases abstracted from patient records, the students worked through 173 computer simulated cases and a posttest of 40 patient cases. The students received no feedback, probability feedback (correct probability of cardiac death for each case), cognitive feedback (the correct cue weights compared with their own weights derived from the previous set of cases), or both types of feedback. Students who received probability feedback markedly improved both base rate calibration and discrimination. Those who received only cognitive feedback showed no improvement over control on any of the measures of learning. All subjects were highly consistent in their weightings. The superiority of probability feedback differed from previous findings that cognitive feedback was essential for mastery of multiple-cue-probability learning tasks. The information on cue-outcome relationships given by cognitive feedback may be more useful when these relationships are complex and the combining rule is not known, while the precise outcome information provided by probabilistic feedback is more useful when the combining rule is known and the cue-outcome relationships are straightforward. Thus, the optimal method of learning depends on the nature of the task. PMID- 1513213 TI - Validation of a model of breast cancer screening: an outlier observation suggests the value of breast self-examinations. AB - As part of a validation of a mathematical model of breast cancer, the Health Insurance Plan of Greater New York (HIP) randomized controlled trial of breast cancer screening and the uncontrolled Breast Cancer Detection Demonstration Projects (BCDDP) trial were simulated. Model predictions were in accord with the nine-year survival experience of women in the HIP trial, and, with the exception of women 40-44 years old, with HIP data on 18-year survival. Five-year survival rates of screen-detected cases in the BCDDP were very close to the model's predictions. However, the model did not predict the high survival rate of women who had interval cancers in the BCDDP. By the end of the BCDDP, almost 85% of the participants performed breast self-examination (BSE) regularly. Consistent with this observation, an appealing hypothesis to explain the high survival rate of women who had interval cancers is that BSE is of value in detecting breast cancers earlier. Consideration of model outliers can be of value in increasing understanding of the phenomena being modeled. PMID- 1513214 TI - Estimating confidence intervals of likelihood ratios. PMID- 1513215 TI - DNA debate. PMID- 1513216 TI - 'No fault' compensation for medical accidents. PMID- 1513217 TI - Scientific fraud: the McBride case. AB - Scientific fraud has occasionally been reported in Australia. The most recent case involved Dr William McBride, a prominent Sydney obstetrician who became well known in medical research for his part in drawing attention to the teratogenic effects of thalidomide. It is still not clear how much of McBride's later activities were fraud and how much poor quality research. The findings of the Inquiry into the matter (Gibbs et al., 1988) have considerable importance for the conduct of private research organizations, publication procedures of research journals, the role of assistants in research projects, collaboration between laboratories, and methods for inquiring into allegations of malpractice. The present paper is based on the Inquiry report. PMID- 1513218 TI - The reasons why suspects confess during custodial interrogation: data for Northern Ireland. AB - This study looks at the reasons offenders give for having confessed during police interrogation. A number of hypotheses were tested, following the work of Gudjonsson and Petursson (1991) on an Icelandic prison sample. The subjects were 80 offenders who were serving prison sentences in Northern Ireland for violence, sex or property offences. The subjects completed the Gudjonsson Confession Questionnaire. All of the hypotheses tested were supported, indicating that there are three primary factors associated with the reasons why criminals make confessions during interrogation. These factors are referred to as Internal Pressure, External Pressure and Proof. The factors were found to be associated with the type of offence committed and the attitude of the offender towards his confession. PMID- 1513219 TI - Who commits matricide? AB - The authors studied sixteen men who committed matricide. Fifteen out of sixteen cases had a diagnosis of schizophrenia and the remaining patient had a diagnosis of schizophrenia with personality disorder. All were single at the time of the matricide. Data indicate an intense conflict-laden and ambivalent relationship between the majority of patients with their mothers. Thirteen out of sixteen cases described their mothers as quite domineering and demanding but the EMBU inventory revealed that the Matricidal group differed from the Control group in how tolerant they saw their parents. The sample as a whole saw mothers were more over-involved, overprotective, tolerant, affectionate, stimulating, performance orientated and shaming. The matricidal group differed from the control group in the way they viewed the difference between mother and father on various scales, like over-involved, tolerant, affectionate and performance-orientated. The matricidal groups' mothers were found to be more over-involved, tolerant, affectionate, and fathers more abusive. Mothers in the control group were more performance-orientated. PMID- 1513220 TI - Altered collagen (fibrinoid change) at the site of post-mortem injuries. AB - The terms fibrinoid degeneration and fibrinoid substance were first introduced by Neumann in 1880 to describe some alterations in the staining characteristics of collagen. Collagen fibres which have undergone this change are eosinophilic, homogeneous and take some of the tinctorial properties of fibrin. Lendrum et al. (1962) developed Martius-Scarlet-Blue (MSB) stain, which is preferentially taken up by fibrin. The principle of the method described by Lendrum and his colleagues is the use of acid dyes of different molecular size (Martius yellow, Brilliant Crystal Scarlet 6R, methyl blue) in accordance with the alteration in structure of fibrin at different stages of development. The newest fibrin likely to be found in sections is presumably the fine network of postmortem fibrin. Much of this takes a yellow stain with the MSB method, as do erythrocytes. Slightly older fibrin (16 hours) takes a bright red stain with the MSB. Complete validity of the method depends on prolonged fixation in formal-sublimate. It gives brilliant staining with acid dyes and enhances metachromasia. In the Department of Forensic Medicine in Leeds it was noticed that an alteration in collagen staining with MSB stain was taking place in samples collected from different kinds of injuries, e.g. ligature marks, electrical injuries and burns. Similar changes were only occasionally seen in abrasions. It was therefore decided to inflict different kinds of injuries on the skins of rats and to fresh pieces of human skin in vitro, to observe any alterations in collagen staining with MSB and to assess the significance of these changes in relation to the timing of injuries.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1513221 TI - Mental impairment in the West Midlands. AB - The case records of 55 people from the West Midlands (UK) fulfilling the Mental Health Act 1983 criteria for mental impairment or severe mental impairment, were studied. Most were young men with mild mental retardation. 73 per cent were resident in (or on leave from) mental handicap hospitals, and 27 per cent resident in special hospitals. 29 per cent were subject to a Restriction Order. Most had lived in hospital for more than six years. The commonest problem behaviours were aggression, property offences and inappropriate or offending sexual behaviour. 31 per cent were mentally ill or had a past history of mental illness. A diverse range of services appears necessary to meet the needs of this group of people. PMID- 1513222 TI - Death certification of problem drinkers. PMID- 1513223 TI - Besieged by devils--thoughts on possession and possession states. AB - Aspects of possession are reviewed in historical, cultural and clinical contexts. Consideration is given to differential diagnosis and management. It is suggested that a multi-disciplinary approach is required for a condition that stands at the boundaries of psychiatry. Two quotations from Elizabethan playwrights are relevant to the theme of this paper: 'Beware you do not conjure up a spirit you cannot lay' Ben Johnson, The New Inn (Act III, Scene ii) 'Farewell the tranquil mind: farewell content.' Shakespeare, Othello (Act III, Scene iii). PMID- 1513224 TI - A study of child homicide over two decades. AB - The child homicides which were notified to the Leeds University Department of Forensic Medicine between 1970 and 1989 were studied. There were 131 cases, and information regarding age of victim, mode of death and post-mortem evidence of previous abuse was noted. The incidences of child homicide varied between 3 and 11 cases per year; the first three years of life providing the majority of cases. Blunt injury accounted for almost half of the deaths, whilst 34 per cent of cases showed evidence of previous physical or sexual abuse. In infant homicide (i.e. under one year of age) a pattern emerged which has previously been described as the 'shaken baby syndrome'. PMID- 1513225 TI - The Hillsborough football disaster and claims for 'nervous shock'. AB - The article investigates the scope for 'nervous shock' claims consequent on negligently inflicted injury, in the light of the Hillsborough disaster. It analyses the existing case law, including the first instance and Court of Appeal judgments in litigation arising from the disaster (for the House of Lords judgment, see Addendum). Its main purpose is to show that several of the arguments and conclusions in these judgments are driven by considerations of policy rather than principle, and primarily by a concern to prevent the 'floodgates of litigation' from opening. It is submitted that greater attention to medical perspectives on psychiatric illness would reveal that this concern is overstated and that a more principled approach would not have the adverse consequences predicted. PMID- 1513226 TI - Epilepsy and criminal law: a supplementary comment. PMID- 1513227 TI - Lethal cardiac tamponade due to aortotomy wound dehiscence after cardiac valve replacement: a forensic presentation. AB - Lethal cardiac tamponade due to aortotomy wound dehiscence after cardiac valve replacement (CVR) are apparently unreported in the recent literature. An uncommon example of delayed non-valvular lethal complication of CVR occurring in the early out-patient period is reported here. The forensic aspects of wound dehiscence in cardiovascular surgery for cardiac valve replacement are discussed, and complemented by a study of the fracture ends of suture material in wound breakdown associated with the suture failure. PMID- 1513228 TI - XYY genotype and crime: 2 cases. AB - The presence of 47, XYY genotype has stimulated much debate as to whether these men are more likely to indulge in criminal and violent behaviour than 46, XY males. Two cases of XYY men who had committed murder are described, and the current literature regarding criminality and psychopathology in XYY males is reviewed. It is important that Forensic Psychiatrists with XYY patients are aware of these issues as the link between XYY genotype and criminality may be raised in court. PMID- 1513229 TI - Body packing presenting as sudden collapse. AB - Cocaine is one of the most rapidly growing drugs of abuse and with it comes an ever-increasing sophistication in concealment from Customs and Police, and may even result in clinicians failing to detect the concealment of packages within the intestinal tract or other body orifices. We present one such case where death arose from rupture of a package of cocaine within the rectum. PMID- 1513230 TI - Informed consent: the law. PMID- 1513232 TI - [Characteristics of air retention by different extracorporeal filters during artificial circulation]. AB - The paper concerns the present-day problem of estimating the efficiency of the functioning of extracorporeal filters in artificial circulation. A method for laboratory studies of extracorporeal filters is offered. The results obtained with the use of the method are provided in order to compare air retention by modern filters. The interference-killing feature and practical feasibility with the use of the popular standard equipment should be attributed to undoubtful advantages of the method suggested. The data obtained are of interest both for users of extracorporeal filters and those who are engaged in the development of the equipment for artificial circulation. PMID- 1513231 TI - [Radionuclide methods of measuring mineral contents in the bone tissue]. AB - Over the recent 10-15 years, osseous densitometers intended for measuring the content of minerals in osseous tissue have become very popular abroad. To record statistically significant changes in an osseous mineral, these devices should have reproducibility (variation rate) exceeding 2%. Mono- and biphoton densitometers may be distinguished by the type of the applied radionuclide. Biphoton densitometers are advantageous since they permit examining any part of the skeletal system of the patient or the whole body. Biphoton absorptiometry is based on measuring the transition of photons of two energies via the medium that largely consists of the two materials bone and soft tissue. The authors describe the results of examining parts of the peripheral skeleton with the aid a laboratory sample of a biphoton osseous densitometer for the peripheral skeleton. PMID- 1513233 TI - [Optimal correlations of design parameters and metrological characteristics of piston spirometers]. AB - Sensitivity parameters, the threshold of response and shift pressure for "rolling seal" spirometers reach the optimum according to the criterion for minimizing the weight of its moving parts. As the result of this, essential reserves of the design can be used, which permits one to substantially improve the methodological and metrological conditions of lung functional tests. PMID- 1513234 TI - [Centrifugal blood pumps (new possibilities of design improvement)]. AB - Based on an analysis of 300 world information sources, 19 types of centrifugal blood pumps were ascertained. Five new designs suggested have an idea in common: combination of the inlet of the disk pump and of the outlet of the impeller pump. This allows uniting the merits of the above pumps and excluding their shortcomings. The designs suggested make it possible to solve the two basic problems: hemolysis and thrombogenesis inside the pumps. The use of the pumps designed on such a basis will afford a simple and reliable approach to heart function replacement. PMID- 1513235 TI - [A method of electric simulation of the radionuclide dilution curve]. AB - The authors demonstrate a possibility of electric simulation of the radionuclide dilution curve for the laminar blood flow. The time required for the indicator mixing, the mean time of blood circulation, and transmission function of circulation in an organ can be derived as a result of such simulation. PMID- 1513236 TI - [Equipment for artificial purification of physiological fluids: current status and developmental trends]. AB - Modern equipment for artificial purification of physiological fluids is viewed as a multiplicity of constructively and functionally interrelated processors of the bioartificial body. The processors include automated control elements (perfusion, infusion and of normalizing action) and disposable actuating elements (main circuits, dialyzers, hemo- and plasma filters, sorption and ion-exchange columns, heat exchangers). Prospective trends in the development are outlined: preferable use of purification methods with energy controlling media; regeneration of dialysate and ultrafiltrate; universalization of functional potentialities in technically and economically derived constructive redundancy, computerization. PMID- 1513237 TI - [A device for automatic selection of exposure in photographing endoscopic objects]. AB - The author reviews the basic outfits for exposition automation as applicable to endoscopy. Regards the main technical difficulties that may occur in the development of such outfits. The conclusion is made that validity of colour rendition of endoscopic objects on the film can be attained, provided the light characteristics of the central (priority information bearing) and peripheral areas of an object are taken into account. The structural block diagram of the appropriate outfit for exposition automation in endoscopy is under discussion. PMID- 1513238 TI - [A device for reproducing lower jaw movements]. AB - A simulator of lower jaw movements is described. The device developed and manufactured by the authors presents a carcass which carries an electric drive, an indexing mechanism, and seats for installation of the models or natural preparations of the lower jaw. The parameters of the movement of the lower bearing seat are as follows: lowering, displacement, lifting, and returning to the initial position. The maximum lateral displacement is 10 mm, the vertical one is 18 mm. The seat is capable of making 12 to 30 movements per minute. The device is intended for trying different treatment methods for mandible diseases and injuries. PMID- 1513239 TI - [Features of the use of endoscopic spectrofluorimeter]. PMID- 1513240 TI - [A device for peritoneal dialysis]. PMID- 1513241 TI - [A device for determination of static load tolerance by patients who have had myocardial infarct]. PMID- 1513242 TI - [Software for automatization of the studies of the gastrointestinal tract]. PMID- 1513243 TI - [A device for intragastric pH-metry and impedance-metry]. PMID- 1513244 TI - [New medical lamps based on halogen incandescent lamps]. PMID- 1513245 TI - [A device for measuring nonuniformity of the dose field of ionizing radiation]. AB - The authors describe a device for measuring the dose field in the beam section of ionizing radiation. The device consists of an immovable bench mark detector and the two detectors: a movable one and a photodiode placed on a tele- and separately movable carriage. The device affords defining the correspondence of radiation and light fields. PMID- 1513246 TI - [A comparative analysis of schemes of the coordinate scale of present-day computerized x-ray tomographs]. AB - A scheme-technical, computational and experimental analysis has been made of different schemes of the coordinate scale of modern computer-aided x-ray tomographs. The authors provide evidence for the concept with the following subdivision: (a) the coordinate scale is divided by a closed ring rule with an insignificant number of bench mark holes; (b) an electronic device which divides the distance between the holes of the rule according to the required number of small-sized samples. The schemes of the indicated concept implementation permit choosing an adequate decision for the scanning systems with different arrangements and parameters. PMID- 1513247 TI - Design and evaluation of shielded gradient coils. AB - Techniques are described for the design of shielded gradient coils for superconducting MRI systems. These design methods are suited for constructing the most efficient gradient coil that meets a specified homogeneity requirement. Tradeoffs in coil design of efficiency with coil size and gap size are discussed. Residual eddy currents from coils constructed with a finite number of wires are calculated and give guidelines for the construction of efficient, whole-body gradient coils. PMID- 1513248 TI - Volume-selective proton MRS in vertebral bodies. AB - Volume-selective 1H magnetic resonance spectra of small volume elements of (13 mm)3 positioned in lumbar vertebral bodies have been investigated in 15 healthy persons of different ages and sexes and in 11 patients with leukemia using double spin-echo sequences. Signal intensities and positions of the spectral lines have been evaluated. Interindividual spectra of VOI located in the center of vertebral bodies, intraindividual spectra of central VOI in different vertebral bodies, and spectra of different localizations within the same vertebral body have been compared as well as spectra before and partly after cytostatic treatment in leukemia patients. Unexpected phenomena of the signal shapes have been found. The water signal distributions in healthy persons compared to patients after bone marrow transplantation show significant differences. The success of the cytostatic treatment in cases of leukemia is accompanied by an increase in the intensity of the lipid signals and a decrease in the water signals. PMID- 1513249 TI - Dynamic studies of gadolinium uptake in brain tumors using inversion-recovery echo-planar imaging. AB - Echo-planar imaging has been used to observe the dynamics of Gd-DTPA uptake in brain tumors. It has been possible to examine both vascular uptake and diffusion across the blood-brain barrier in a single experiment, by using the IR-MBEST echo planar sequence which combines a high temporal resolution (approximately 3 s) with strong T1 weighting. To model the uptake it is necessary to know the arterial concentration of Gd-DTPA; in this study the signal in the sagittal sinus was measured to avoid the need to take repeated blood samples. The time constant for transfer across the blood-brain barrier was measured to be between 20 and 1050 s for different tumors. The results of the modeling correlated with the results of other assessments of tumor vascularity. PMID- 1513250 TI - Analysis of the evolution of focal cerebral ischemia in the rat using the eigenimage filter. AB - The eigenimage filter was used to evaluate the results of a MRI study of cerebral ischemia in a rat model. This linear filter segments a desired feature in an image sequence from other features which may interfere with its observation. The animals were imaged temporally, after occlusion of the middle cerebral artery, to investigate the evolution of the ischemic process. The temporal evolution of ischemia was evaluated by analysis of the "eigenimages," calculated T2 and T1 map images, and images for the angles between signature vectors defined in the eigenimage technique. The eigenimages and angle map images demonstrated an improved visibility of the lesion at all time points, as compared to the original images and T2 and T1 map images. The eigenimages also demonstrated signal intensity changes within the area of ischemia. These changes are speculated to be related to variations in local cerebral blood flow resulting in varying degrees of tissue damage. The eigenimage intensities and the angles between signature vectors demonstrated time-related changes similar to the T2 and T1 values. Since the eigenimage filter and angle calculations are not dependent upon physical models (like T2 and T1), and the errors associated with these models, they may be preferable as methods for tissue characterization. PMID- 1513251 TI - Direct measurement of spin-lattice relaxation times of phosphorus metabolites in human myocardium. AB - T1 values of phosphorus metabolites visible in human cardiac 31P-MR spectra were determined in 12 volunteers at 1.5 T. Consecutive spectra were acquired with varying pulse repetition time (TR) from 1.6 to 24 s; volume selection was achieved with ISIS. T1's of creatine phosphate (CP), [gamma-P], [alpha-P], and [beta-P]ATP, 2-3 diphosphoglycerate, and phosphodiesters were 6.1 +/- 0.5, 5.4 +/ 0.5, 5.5 +/- 0.5, 5.8 +/- 1.0, 7.6 +/- 1.0, and 5.0 +/- 1.0 s, respectively. CP/ATP ratios showed little change with varying TR; linear regression of CP/ATP vs TR was of borderline significance (r = 0.28, P = 0.06). T1's for CP and ATP were also determined in standard solution (20 mM CP, 10 mM ATP) yielding T1CP of 8.7 +/- 0.2 and T1[gamma-P]-ATP of 9.9 +/- 0.7 s. Thus, T1's for CP and ATP were similar at 1.5 T in both human heart and standard solution. In human cardiac 31P MR spectra, CP/ATP ratios may need little correction for partial saturation. PMID- 1513252 TI - Spatial heterogeneity of the metabolic response of RIF-1 tumors to a vasoactive agent evaluated in vivo by one-dimensional 31P chemical-shift imaging. AB - Localized 31P NMR spectroscopy was used to evaluate the spatial heterogeneity of the metabolic response of RIF-1 tumors to hydralazine. Volume localized 31P spectra were obtained from subcutaneous RIF-1 tumors using one-dimensional chemical-shift imaging, before and 20 min after treatment with 5 mg/kg hydralazine, administered intravenously. Following treatment all of the tumors showed an overall decrease in the ratio of nucleoside triphosphate (NTP) to inorganic phosphate (Pi) and a decrease in pH. However, spatial localization revealed that the reduction in NTP/Pi was not uniform within some tumors. This was partly due to regional differences in the levels of metabolites existing before treatment. Normal tissue adjacent to the tumor did not show a significant decrease in high-energy metabolites or pH. PMID- 1513253 TI - Proton magnetic resonance spectroscopy of human brain: applications to normal white matter, chronic infarction, and MRI white matter signal hyperintensities. AB - A modified ISIS method, for image-selected localized proton magnetic resonance spectroscopy (1H MRS), was used to determine the ratios and T2 relaxation times of proton metabolites in normal subjects and in patients with chronic infarction and MRI white matter signal hyperintensities (WMSH). First, in patients with cerebral infarctions, increased concentrations of lactate were found in the majority of patients, and N-acetyl aspartate (NAA) was reduced to a significantly greater extent than choline (Cho) or creatine (Cre). For TE = 270 ms, the raw ratios of Cho/NAA, Cre/NAA, and Lac/NAA were significantly (P less than 0.05) increased from 0.23 +/- 0.02 (mean +/- SE), 0.20 +/- 0.01, and 0.05 +/- 0.01, respectively in the normal group to 0.39 +/- 0.08, 0.37 +/- 0.05, and 0.48 +/- 0.15 in the stroke group. Also, the T2 relaxation time of creatine was significantly (P = 0.007) increased from 136 ms in normal white matter to 171 ms in cerebral infarcts. Second, in patients with WMSH, no significant change of the proton metabolite concentrations could be detected with the exception of the choline which was significantly (P = 0.003) altered. The Cho/NAA ratio, after T2 and excitation profile correction, increased from 0.47 +/- 0.02 in the normal group to 0.64 +/- 0.05 in the WMSH group. Third, in normal white matter, the concentration of N-acetyl aspartate, choline, and lactate was estimated to 11.5, 2.0, and 0.6 mM, respectively, by assuming a total creatine concentration of 10 mM. PMID- 1513254 TI - Partial RF echo planar imaging with the FAISE method. I. Experimental and theoretical assessment of artifact. AB - The fast acquisition interleaved spin-echo (FAISE) method is a partial RF echo planar technique which utilizes a specific phase-encode reordering algorithm to manipulate image contrast (Melki et al., J. Magn. Reson. Imaging 1:319, 1991). The technique can generate "spin-echo" like images up to 16 times faster than conventional spin-echo methods. However, the presence of T2 decay throughout the variable k-space trajectories used to manipulate T2 contrast ensures the presence of image artifacts, especially along the phase-encode direction. In this work, we experimentally and theoretically examine the type and extent of artifacts associated with the FAISE technique. We demonstrate the existence of well-defined minima of phase-encode ghost noise for selected k-space trajectories, examine the extent of blurring and edge enhancement artifacts, demonstrate the influence of matrix size and number of echoes per train on phase-encode artifact, and show how proper choice of FAISE sequence parameters can lead to proton density brain images which are practically indistinguishable from conventional spin-echo proton density images. A comparison of contrast between FAISE and standard spin-echo methods is presented in a companion article referred to as II. PMID- 1513255 TI - Partial RF echo-planar imaging with the FAISE method. II. Contrast equivalence with spin-echo sequences. AB - The fast acquisition interleaved spin-echo (FAISE) sequence and its dual-echo version (DEFAISE) are partial RF echo-planar methods which utilize a specific phase-encode reordering algorithm to manipulate T2 contrast via an operator controlled pseudo-echo time, pTE. The repetition time, TR, between successive applications of the Carr-Purcell-Meiboom-Gill (CPMG) echo trains used in FAISE may be reduced to introduce T1 weighting. To quantitatively determine the extent to which FAISE T1 and T2 contrast characteristics agree with spin-echo methods, signal intensities from FAISE acquisitions were compared with signal intensities from equivalent CPMG acquisitions. In phantoms and in human heads, the contrast characteristics of FAISE are found to be highly correlated with that obtained with equivalent CPMG sequences. However, conventional SE sequences generally utilize longer echo spacings than employed with FAISE/CPMG. Thus, echo spacing dependent mechanisms such as spin-spin coupling and magnetic susceptibility lead to some differences in contrast between conventional SE and FAISE. Finally, FAISE appears to be more sensitive to magnetization transfer effects than conventional SE sequences since more off-resonance irradiation is applied to individual slices during multislice acquisitions. PMID- 1513256 TI - Single-shot GRASE imaging without fast gradients. AB - Based on the CPMG sequence, gradient- and spin-echo (GRASE) echo train length is limited by T2 decay rather than the T2* decay and phase error in echo-planar techniques, permitting a longer image acquisition period. An ultrafast GRASE sequence, utilizing a single excitation, generates a 128 x 56 true T2-weighted image in 200 ms on an unmodified commercial scanner without fast gradient switching, extreme field homogeneity, or fat signal suppression. PMID- 1513257 TI - Recursive RF excitation. AB - We have investigated the properties of a recursive process in which the output signal from a given RF excitation pulse may be used as the input (excitation) pulse of a subsequent iteration. This recursive excitation technique increases contrast and improves feature segmentation for the purpose of motion tracking. PMID- 1513258 TI - 31P NMR spectroscopy of the human heart at 4 T: detection of substantially uncontaminated cardiac spectra and differentiation of subepicardium and subendocardium. AB - 31P NMR spectroscopy of the human heart was undertaken at 4 T to investigate whether spectra localized exclusively to the myocardium can be obtained. Utilizing a Fourier series window approach to spectroscopic imaging, we find that at least two layers across the anterior left ventricle wall can be detected, with voxel sizes of about 8 cm3. PMID- 1513259 TI - Rapid T1 estimation using tagged magnetization-prepared gradient-echo MR imaging. AB - A technique for estimation of the longitudinal relaxation time of a large homogeneous object with an acquisition time of 4 s or less was developed by combining spatially selective rf tagging pulses with a T1-weighted magnetization prepared gradient-echo sequence. Multiple 5-mm-wide tagged areas are laid orthogonal to the imaging section of interest. The contrast between each tag and the untagged regions differs because each tag is produced at a different time. The T1 value is determined from the nulling time at which tagged and untagged areas have no contrast. PMID- 1513260 TI - Intracellular localization of Staphylococcus aureus within primary cultured mouse kidney cells. AB - Staphylococcus aureus Cowan I was incubated with monolayers of cells derived from several portions of mouse kidney, and found to be ingested by all types of the renal cells. Intracellular localization of S. aureus was determined by resistance of intracellular cocci against lysostaphin digestion and confirmed by electron microscopy. From renal medulla, three morphological variants of the hyperosmolarity-tolerant (HOT) cells were obtained. The rate of cocci-ingesting cells varied from 16.9% to 93.4% among these of the HOT cells at the end of 3-hr incubation. From renal cortex, three morphological variants of epithelial cells grew in medium RK-1. Among them, only the cells on the edge of colony ingested Cowan I, while the epithelial cells on the center of colony ingested few cocci. Transferred from medium RK-1 to MEM supplemented with 10% FBS, part of the cortical cells changed into fibroblast-like appearance and obtained the capacity to ingest Cowan I. This result may indicate the correlation between ingesting capacity and cellular morphology. From a glomerulus, epithelial (GE) cells and fibroblast-like (GF) cells were obtained. The GE cells ingested not only S. aureus Cowan I but Staphylococcus epidermidis and Staphylococcus saprophyticus after 30-min incubation, while the GF cells, like both of the HOT cells and the cortical cells, ingested only S. aureus. These results suggest a possibility that S. aureus is located within nonprofessional phagocytes during its infection and intracellular coccus plays an important role in its pathogenicity. PMID- 1513261 TI - Analysis of borderline-resistant strains of methicillin-resistant Staphylococcus aureus using polymerase chain reaction. AB - Identification of methicillin-resistant Staphylococcus aureus by drug susceptibility tests alone poses a serious problem, because a considerable number of clinical S. aureus isolates are borderline resistant to methicillin. To circumvent this problem, we have developed a quick and sensitive method of PCR amplification for the detection of mecA gene, which, coding for PBP2', is the specific genetic element of methicillin-resistant Staphylococcus aureus. This method made it possible to identify MRSA strains in a short time using as few as 30 cells as a starting material for template DNA. Using this method, we found that the strains of borderline methicillin-resistance could be accurately identified. We also found one S. aureus clinical strain, T3, which lacked mecA gene in spite of its resistance to methicillin. PMID- 1513262 TI - Relationship between an 85 kDa protein and the protective effects of Mycoplasma pneumoniae. AB - In the immunoblot analysis, sera from patients infected with Mycoplasma pneumoniae reacted with the 168 kDa (P1) and the 85 kDa proteins of virulent strain FH-P24 and P24-S1 mutant strain but not with the 85 kDa protein of P24 S11. Sera of hamsters and BALB/c mice, which had been immunized with live vaccines, were tested. In FH-P24 immunized animals, 100% or 80%, and in P24-S1, 40% of hamsters and 60% of BALB/c mice, developed antibodies against the 85 kDa protein, but antibodies were not detected in sera of P24-S11 immunized animals. The correlation between the development of antibodies to 85 kDa protein in the sera of vaccinated animals and the effects of protection by living vaccines were suggested. PMID- 1513263 TI - Definition and application of a histopathological scoring scheme for an animal model of acute Mycoplasma pneumoniae pulmonary infection. AB - A histopathological scoring system was developed to assess the pathology of acute Mycoplasma pneumoniae pulmonary infection in a hamster model. A final score per animal (ranging 0-26) is obtained by averaging scores from each lung which have been accumulated by the addition of subscores from the assessments of quantity and quality of peribronchiolar and peribronchial infiltrates, luminal exudates, perivascular infiltrates, and parenchymal pneumonia. The scoring scheme was then applied to test the ability of a heat-killed inoculum to induce pulmonary pathology and to the trial of a 43 kDa protein-associated antigen as a vaccine immunogen. A heat-killed inoculum delivered by both intratracheal and intranasal routes did not induce pulmonary pathology compared to a live inoculum (respective mean scores 0.1, 6.7; P less than 0.01). Animals prevaccinated with the 43 kDa antigen developed an accentuated pathological response after live challenge compared to those unvaccinated (respective mean scores 16.8, 5.8; P = 0.00007). Hypersensitization to growth medium components may, however, have contributed to the accentuated disease since the lungs of vaccinated animals challenged with culture-negative media also were affected (mean score 5.4). Reproducibility of the scoring system was measured by duplicate reading of histology slides which were randomized to the observer upon the second reading (r = 0.93; P = 0.000009). The scoring system has the ability to differentiate disease severity in small groups of animals. PMID- 1513264 TI - Augmentation of host resistance to Candida albicans infection in ascites tumor bearing mice. AB - We found that the number of peripheral blood polymorphonuclear leukocytes (PMN) dramatically increased in both sarcoma 180 (S-180) and MM-46 mammary carcinoma (MM-46) ascites tumor-bearing mice, and mice required a remarkable resistance to Candida albicans infection via intravenous route. When the resistance was determined by number of cells of C. albicans in the kidney, a significant decrease in the number of fungal cells was observed in the kidneys of infected ascites tumor-bearing mice. An increase of active oxygen levels of PMN from ascites tumor-bearing mice was observed, suggesting that this factor is important in developing of resistance in ascites tumor-bearing mice. Additionally, a culture supernatant of tumor cells co-cultivated with bone-marrow cells in vitro increased the number of granulocytes and macrophages differentiated from the bone marrow cells. PMID- 1513265 TI - An activity which restores theta toxin activity in some theta toxin-deficient mutants of Clostridium perfringens. AB - Group a mutants of Clostridium perfringens are deficient in theta toxin but release a dialyzable substance ("substance A"), which restores theta toxin activity to group b mutants, into a culture supernatant; group b mutants are defective in "substance A" release. "Substance A" activity appeared in the exponentially growing phase of group a mutants and disappeared in the stationary phase. "Substance A" activity was most stable at pH 5.0 and 0 C and even increased threefold in the first 5 hr, but gradually decreased during the following 15 hr. It was quickly inactivated at neutral and higher pHs at 0 C. PMID- 1513266 TI - Differentiation between Mycobacterium avium and Mycobacterium intracellulare by thin-layer chromatography of lipid fraction after incubation with [35S]methionine. AB - Mycobacterium avium and Mycobacterium intracellulare are differentiated from each other by thin-layer chromatography of lipid fraction extracted after incubation with [35S]methionine. The former contained a petroleum ether-soluble sulfolipid and the latter did not. PMID- 1513267 TI - Existence of phosphoenolpyruvate: carbohydrate phosphotransferase systems in Lactobacillus fermentum, an obligate heterofermenter. AB - The presence or absence of the phosphoenolpyruvate: carbohydrate phosphotransferase system (PTS) in obligately heterofermentative group III lactobacilli including Lactobacillus brevis (3 strains), L. buchneri (2 strains) and L. fermentum (3 strains) was surveyed systematically for a series of sugars utilizable by these organisms. Contrary to common expectation, PTSs were found in two strains of L. fermentum: sucrose-PTS in one strain; sucrose- and mannose-PTSs in the other. All these activities were found to be constitutive. PMID- 1513268 TI - Genetic variation among Malaysian isolates of Salmonella typhi as detected by ribosomal RNA gene restriction patterns. AB - Genetic variation among Malaysian isolates of Salmonella typhi was determined by analysis of ribosomal RNA gene restriction patterns. Of the 20 isolates analyzed, eight different pattern combinations were detected. The amount of variation observed was also dependent upon the restriction endonuclease used; PstI produced more different patterns than did SmaI. The results suggested that disease activity was due to a number of different clones circulating simultaneously rather than a single strain. Further implications of the data are discussed. PMID- 1513269 TI - Conspicuous ingestion of Staphylococcus aureus organisms by murine fibroblasts in vitro. AB - A conspicuous adhesion of Staphylococcus aureus organisms to murine cutaneous fibroblasts and NIH/3T3 cells cultured in vitro and subsequent ingestion of S. aureus organisms by these fibroblasts are described. In the present experimental system, only fibroblasts-adhering S. aureus organisms were efficiently ingested by fibroblasts unlike S. epidermidis and S. saprophyticus. These findings might suggest a correlation between the pathogenesis of S. aureus and its intracellular localization in non-professional phagocytes such as fibroblasts in a special reference to its higher pathogenicity than those of coagulase negative counterparts. PMID- 1513270 TI - The role of aromatic hydrocarbons in the genesis of breast cancer. AB - The incidence of breast cancer in women has increased dramatically over the last decade. Epidemiological markers of this increased incidence include: endocrine related phenomena (early menarche, age of first parity and age of menopause); exposure of the breast to X-radiation; and a group of seemingly disparate factors -urban residence, dietary selection and alcohol consumption. Although experimental breast cancer may be induced by estrogenic hormones, X-radiation and aromatic hydrocarbons, only aromatic hydrocarbons have not been previously implicated in human mammary carcinogenesis. The seemingly unrelated human factors can best be understood by examining the role of breast tissue in aromatic hydrocarbon metabolism. Aromatic hydrocarbons are important environmental chemicals produced by the incomplete combustion of hydrocarbons for use in energy production. Benzene, benz(a)pyrene, dibenz(ah)anthracene and 1-nitropyrene, known experimental breast carcinogens, are produced in this way. Human exposure to aromatic hydrocarbon metabolites induces and promotes altered DNA by mechanisms described as increased intracellular pro-oxidant production as well as direct adduction to DNA. The breast is anatomically embedded in a major fat depot which stores and concentrates aromatic hydrocarbons and can metabolize these hydrocarbons to carcinogenic metabolites. Ductal cells concentrate these metabolites and themselves become target cells for carcinogenesis. Some lifestyle factors increase the amount of carcinogens produced or enhance their activity. A unitary model for mammary carcinogenesis in humans as well as in experimental carcinogenesis is hypothesized. If correct, the hypothesis would account for some of the increase in breast cancer incidence in industrial countries--and would suggest environmental and dietary modifications that would inhibit hydrocarbon induced mammary carcinogenesis. PMID- 1513271 TI - Possible roles for nitric oxide in AIDS and associated pathology. AB - The endogenous free radical, nitric oxide (NO), plays a neurotransmitter-like role in vascular endothelium, a second-messenger role in N-methyl-D-aspartate (NMDA)-responsive neurons in the central nervous system (CNS), a neurotoxic role after its release from these neurons, and a cytotoxic role after its release by macrophages. NO also derives from exogenous sources, such as the nitrite inhalants, amyl, butyl and isobutyl nitrite. There is evidence that abuse of nitrite inhalants can affect immunomodulation, and epidemiological studies suggest that such abuse may be a cofactor in the pathogenesis of acquired immunodeficiency syndrome (AIDS). Hitherto, however, the potential role of NO in such pathogenesis has not been examined. This paper presents some current evidence that implicates both endogenous and exogenous sources of NO in AIDS and associated pathology. PMID- 1513272 TI - Mechanisms of adaptive evolution. Darwinism and Lamarckism restated. AB - This article discusses the conceptual basis of the different mechanisms of adaptive evolution. It is argued that only two such mechanisms may conceivably exist, Lamarckism and Darwinism. Darwinism is the fundamental process generating the diversity of species. Some aspects of the gene-centered approach to Darwinism are questioned, since they do not account for the generation of biological diversity. Diversity in biological design must be explained in relation to the diversity of interactions of organisms (or other higher-level units) with their environment. This aspect is usually overlooked in gene-centered views of evolution. A variant of the gene-selectionist approach has been proposed to account for the spread of cultural traits in human societies. Alternatively, I argue that social evolution is rather driven by what I call pseudo-Lamarckian inheritance. Finally, I argue that Lamarckian and pseudo-Lamarckian inheritance are just special cases of faithful replication which are found in the development of some higher-order units, such as multicellular organisms and human societies. PMID- 1513273 TI - A gene for alcohol toxicity, not drinking behavior. AB - Apparently contradictory results concerning association of an allele of a human dopamine receptor gene with alcoholism are explained by the gene's being involved with ethanol toxicity, not drinking behavior. PMID- 1513274 TI - Addiction to nicotine is due to high intrinsic levels of dopamine. AB - Smokers are less likely to develop Parkinson's disease (PD) than is true of non smokers, and PD is the only disease inversely related to smoking. PD is associated with a reduced level of dopamine. Although nicotine can affect the receptors, including dopamine receptors, it seems unlikely that use of nicotine is protective in PD. An alternative explanation is that just as PD is associated with a lower than normal level of dopamine, addiction to smoking is linked with a higher than normal level of dopamine. This high innate level of dopamine facilitates addiction to nicotine. PMID- 1513275 TI - Cell proliferation and carcinogenesis may share a common basis of permeable plasma membrane clusters. AB - Wound potentials increase the surface potential of exposed areas of nearby cells. In these cells, soluble cytoplasmic bases are assumed gradually to move nearer the exposed area. Acidic molecules on the cell surface migrate to points opposite the bases. The image-charged species are mutually attracted to form transmembrane clusters. At clusters, membrane permeability increases and the cell is stimulated to cycle. When the wound heals, its clusters disperse, leaving a small 'permanent' residuum. Permanent clusters initiate cells to malignancy. They have (or develop) lipophilic molecules on both surfaces that help fix them in the membrane. Exposed cells contaminated with polycyclic aromatic hydrocarbon carcinogens (PAH) readily form permanent clusters. At mitosis, clusters on parental plasma membrane pass with that membrane to a daughter cell. Promotion results from many short-term or a single long-term exposure of initiated membranes to abnormal surface charge. Permanent clusters increase on the membrane after repeated wounding, proximity of charged foreign bodies like plastic film or asbestos, or oxidation of surface molecules. Progression requires acceleration of cluster growth so the daughter cell membranes become as leaky at maturity as was the parent membrane. One mechanism suggested involves reversible phosphorylation by membrane-bound kinases; another involves attraction of a basic protein (p36) to the membrane. PMID- 1513276 TI - Sensitivity of latent cancer to chemotherapy. AB - The paper is a review of some cancer patients who were treated successfully by surgery followed by chemotherapy. The cases suggest the hypothesis that early cancer growth following surgery is more sensitive to chemotherapy than the active cancer growth of the original tumor. PMID- 1513277 TI - Hyperfractionated, twice-a-day, radiotherapy may decrease IQ deterioration due to prophylactic cranial irradiation in childhood acute lymphoblastic leukemia: a radiobiological analysis. AB - High cure rates in childhood acute lymphoblastic leukemia (ALL) are being achieved with aggressive systemic chemotherapy and treatment to sanctuary sites including prophylactic cranial irradiation. However, IQ deterioration is a dreaded complication of prophylactic cranial irradiation. IQ deterioration is a late sequela. Since there is evidence--both radiobiological and clinical--to suggest that acute tissue (including tumor) response and late tissue response can be separated by hyper-fractionation, we propose a twice-a-day radiotherapy in prophylactic cranial irradiation of childhood ALL to decrease delayed toxicity. Analysis based on current radiobiological models favors such a treatment scheme. However, only a prospective clinical trial can confirm whether IQ deterioration can be prevented or decreased with hyper-fractionated radiotherapy. PMID- 1513278 TI - Colic, sleep inertia, melatonin and circannual rhythms. AB - Colic is periodic behavior occurring at the end of the day during the first 3 months of life characterized by crying. It is hypothesized that the crying at the end of the day is due to sleep inertia or a state dissociation during which the infant is simultaneously partially awake and partially asleep because of the absence of a melatonin diurnal rhythm. The melatonin timing mechanisms, which codes for day length, is initiated prenatally by the maternal pineal gland, and after 3 months postnatally, the melatonin nocturnal secretion rhythm is maintained by the infant's pineal gland. To record the seasonal variation in day length away from the equator, 12 months are required to complete the melatonin chemical calendar. This circannual process is only 9 months completed at the time of birth, and 3 additional months are needed during which the infant may have difficulty reconciling cues for the timing of evening sleep due to discrepancies between the expected photoperiod derived from the prenatal maternal pineal melatonin circadian rhythm and the postnatally experienced photoperiod. Data is presented showing that the incidence of colic increases with increasing latitude in support of the hypothesis that infant crying at the end of the day during the first 3 months represents the last quarter of a circannual photoperiodic development process. PMID- 1513279 TI - Proposed role of septohippocampal and pallido-habenulo-raphe systems in photoperiodic time measurement. AB - The neuroanatomic substrate for mammalian photoperiodic time measurement (PTM), a primary requirement for appropriately timed seasonal reproductive function, is unknown. It is suggested that the 'comparator' of successive day lengths previously postulated as necessary for PTM may be located within the septohippocampal system, output from which is then directed to reproductive system response elements by way of several possible routes including the pallido habenulo-raphe conduction line. PTM thus requires the integration of an invariant, context-free circadian function subserved by the well-known melatonin generating system with a flexible, context-dependent extracircadian function subserved by the septohippocampal system. The context-dependent neuronal network endows reproductive-system responses with the ability to be modulated by previous photoperiodic history, an ability not possessed by the context-free circadian network proper. Several suggestions for testing the validity of the proposed model are offered. PMID- 1513280 TI - L-arginine: a therapeutic option for AIDS/HIV infection? AB - Numerous studies implicate cellular immunological effector systems in the partial containment of virus replication during the early stages of HIV infection. Immunostimulatory therapeutic regimes designed to enhance virus clearance are therefore theoretically attractive, but are accompanied by the risk of concomitant activation of HIV replication. Supra-normal levels of L-arginine have been shown to induce broad immune stimulation in vitro and in vivo, but do not increase HIV gene expression in vitro. These observations, together with the lack of toxicity of this agent, suggest a novel therapeutic approach to HIV disease. PMID- 1513281 TI - Transgenic domestic animals provide an animal model for rheumatoid arthritis. AB - Production of transgenic domestic animals by microinjection of egg nuclei has permitted the introduction of exogenous genes into the transgenic animal. Pursell et al (1) report severe synovitis, cardiomegaly, dermatitis, renal disease and gastric ulcers in pigs with an expressed bovine growth hormone transgene. I have hypothesized that rheumatoid arthritis (RA) is a disease with initial symptoms to the gamete (2, 3). This hypothesis is supported by data showing a reduced rate of RA in women using oral contraceptives (4, 5) and remission of RA in pregnancy (6). RA in animals resulting from trauma to the gamete would be consistent with this hypothesis. This paper hypothesizes that some of the pathology associated with genetic engineering of livestock can be attributed to a rheumatoid arthritis like spectrum of symptoms. This systemic reaction could be sufficiently similar to human RA to permit the transgenic pig to serve as an animal model of the disease. PMID- 1513283 TI - Calcific aortic stenosis and autonomic dysfunction. AB - With an aging population, calcific aortic stenosis is becoming more important in medical practice. Its cause is unknown. This paper hypothesises autonomic dysfunction is the abnormality underlying the tendency of the aging aortic valve to calcify, a proposition based on 2 main lines of evidence: 1. the similarity between aortic valvular calcification and medial arterial calcification, the latter a condition in whose pathogenesis autonomic dysfunction is implicated; 2. the similarity between the changes of autonomic denervation and those of natural aging in the aortic valve, of which calcific aortic stenosis is an exaggerated form. Autonomic denervation leads to withdrawal of neurotrophic influences from cells and tissues. The resulting changes in function and in structure, it is proposed, give rise to a condition of vulnerability allowing other stresses, such as haemodynamic trauma, to result in calcification. PMID- 1513282 TI - Oxidized LDL ceroid, and prostaglandin metabolism in human atherosclerosis. AB - A noted histological feature of human atherosclerotic lesions upon dissection is the presence of a 'pigment' referred to as ceroid; however the significance of ceroid in human fatty streaks and atherosclerotic plaques is not certain. The research focus to this point has presumed that ceroid synthesis and intracellular accumulation is harmful and may have adverse effects on lesion progression or reversibility. Alternatively, ceroid production may be a defense mechanism employed by cells in the artery wall to prevent uncontrolled synthesis and release of prostaglandins (PGs) or prostaglandin-precursors locally. Export of PGs or PG precursors may promote blood platelet aggregation at the site of export. A feedback inhibition mechanism will arrest the cellular export of prostaglandins, thus ending a potentially disastrous premature clotting event. PMID- 1513284 TI - The synergism of gamma-interferon and tumor necrosis factor in whole body hyperthermia with vitamin C to control toxicity. AB - In a previous paper, the synergism of gamma-interferon and tumor necrosis factor was considered with whole body hyperthermia. Because of the toxic effect of TNF due to oxygen radicals, it is suggested that vitamin C be added. PMID- 1513285 TI - The sometime suppressor gene RB 1. PMID- 1513286 TI - Role of visuo-vestibular interaction in pathological ocular oscillation: new model and control system analysis. AB - Control system engineering is a relatively newer field of engineering which is directly applicable to performance analysis of neuronal networks. Visuo vestibular interaction (VVI) represents a neuronal control system which has most benefited from such analysis. In this paper, we present a new model of VVI derived from our previously reported model by adding cortical pursuit feedback. Mathematical analysis of abnormal eye oscillations and stability analysis of the VVI system provided us with a plausible hypothesis that the pathological ocular oscillations seen in oculopalatal myoclonus and see-saw nystagmus are indeed due to an unstable VVI control system. The former is due to degeneration of the inferior olivary nucleus resulting in loss of cerebellar learning effects, while the latter is due to disruption of the pathway conveying retinal error signals. PMID- 1513287 TI - The loss of estrus behavior in humans: a physiological explanation. PMID- 1513288 TI - An impetus for further developing the role and education of the midwife. PMID- 1513289 TI - Working for patients: further implications for nurse education. AB - The National Health Service and Community Care Act (1990) has focused attention on all aspects of health care. This paper explores the wider implications of the White Paper on nurse education. It examines the issues of student numbers; rationalisation of courses; the impact of contracts; quality control and clinical placements. It further considers the issues of capital assets; educational premises; funding and income generation. The response of schools and colleges of nursing to these challenges has yet to be evaluated. Nurse education is steering an uncertain course in turbulent and uncharted waters. If colleges of nursing are to capitalise on the changes demanded by the White Paper, the prime concern must be the establishment of an advantageous position from which to market viable courses. To this end there must be adequate resources, and control over high quality learning environments. The courses must be educationally led and respond to the learning needs of all students. PMID- 1513290 TI - Teaching research to nurses: issues for tutor training. AB - Research is unknown territory, in too many ways, for many nurses and nurse tutors. It is seen as the province of an elite, using obscure language and esoteric skills with no obvious connection with the world of nursing; in particular, it involves statistics. Pressure for nursing to become a research based profession can make the fear worse; the gap between research and practice generates blame and guilt in addition to fear. It is not surprising that learning and teaching about research can be very difficult for nurses. This article explores sources of bad feelings about research and suggests ways forward in the training of nurse and midwifery tutors, considering course planning and teaching methods, and peer support in and out of the classroom. It also argues for expanding the range of nursing research used to teach about research, incorporating more qualitative methods and drawing more fully on the social science traditions. PMID- 1513291 TI - Theory and practice and the preparation of teachers of nursing. AB - Questions of the relationship between theory and practice frequently occur both within educational and nursing literature and they are the questions that are going to be explored in this paper. Like the double helix, this paper is going to intertwine and interlink nursing and education, since they possess so many similarities and the overall thesis of the paper is that the relationship between theory and practice presents problems because the nature of the problem has been inadequately formulated. The paper falls into four main parts: 1. Four types of relationship between theory and practice. 2. Nursing and education as fields of practice and the nature of fields of practice--implications of this for knowledge, skills, attitudes and values--skills/practical knowledge/knowledge how. 3. Nature of the fields of study and the implications of this for knowledge. 4. Theory and practice--eight possible relationships. The conclusion offers a tentative reformulation of theory and practice in terms of probability and relates this to the preparation of nurses and teachers. PMID- 1513292 TI - An innovatory honours degree programme for nurse teacher preparation: development and evaluation. AB - The implementation of the Project 2000 recommendations in the UK is bringing about change in the role and functions of the nurse teacher in terms of relationships with associated institutions of higher education, with colleagues in both teaching and clinical settings and in terms of the teaching and facilitating strategies employed. As a consequence there has been a reappraisal of nurse teacher preparation. This paper provides a description and an evaluation of an innovatory full-time degree programme that provides advanced study of nursing, behavioural, life and social sciences combined with the study of education and leading to a teaching qualification recordable with the United Kingdom Central Council (UKCC). The development of the BA (Hons) Nursing with Education degree programme at Portsmouth Polytechnic is briefly described and placed in context. The course has been subject to formative and summative evaluation using a range of techniques which are reported in this paper. There is a brief discussion of the action taken on the outcomes of the evaluation. The paper concludes with the identification of issues arising from the evaluation. PMID- 1513293 TI - An exploration of issues relating to feminism and nurse education. AB - This paper explores the issue of feminism in relation to nursing and nurse education. As a result of this exploration, the authors suggest there is a need for a move away from traditional patriarchal approaches to nurse education, towards an educational programme based on empowerment principles that maximises the potential of feminine patterns of thinking. PMID- 1513294 TI - The nurse educator and the legal implications. AB - This paper considers the liability of the nurse educator in her professional work. It begins by exploring the law for liability in giving negligent instructions and advice and the possibility of being liable for harm caused to a patient as a result of negligent teaching. The possibility of being liable if an incompetent student becomes registered and causes harm is also discussed. Liability for giving references on students is also considered and differences in outcomes between true but unsupportive references as against false but supportive ones are analysed. PMID- 1513295 TI - Time management in education. AB - The topic of time management is an area that is very important to today's nurse educationalist, especially with the ever increasing demands being made upon her time. In this paper the writer examines the concept of time management, and some of the issues which should be given due consideration by anyone who is contemplating developing the skills required for success in managing time effectively. The work utilises ideas which enable one to take a problem solving approach to the subject. Here the reader will also find a selection of possible solutions that have been put forward from various sources, many of which the writer has tried herself and found to be extremely helpful in tackling her own problems in this area. One point that is reiterated throughout, is the very personal nature of time management and the fact that it is up to the individual to choose the most useful method in order to achieve an efficient and effective approach to the management of time, hopefully resulting in greater control and equally as important--'peace of mind'. PMID- 1513296 TI - Teaching the skills of assessment through the use of an experiential workshop. AB - Assessment is a key element of the nursing process, yet the skills required to perform a nursing assessment are poorly defined in the literature. Related to this, nurse education does not adequately address how it might be possible to develop in students the skills required to plan individualised care. As a contribution to this important area of nurse education, this paper describes the first term of an assessment course, an important component of which is an experiential workshop. This workshop introduces students to the skills of observation, measurement and testing as used when assessing physiological indicators of health status. The workshop was designed to facilitate an understanding of the connection between the students' knowledge of biological sciences and nursing practice. PMID- 1513297 TI - An examination of the factors influencing the choice of one college of nursing in choosing an institute of higher education with which to link. AB - This paper examines the factors influencing the choice of one College of Nursing when linking with an Institute of Higher Education, from which general principles can be drawn. The College is situated in Central London, within a Special Health Authority at a post graduate centre. The College currently offers courses in clinical nursing leading to English National Board certification, but is hoping to expand its courses in the near future. Influencing factors are examined in the light of the final decision using Roby's Deliberative Model. PMID- 1513298 TI - Mentors, not assessors. AB - The English National Board supports the development of a mentorship scheme for Project 2000 courses. The lack of clarity regarding the role and function of mentors continues. This paper suggests that the role of mentor should be restricted to assisting, befriending, guiding, advising and counselling students, and should not incorporate the roles of supervisor, assessor, preceptor or facilitator. Some of the difficulties experienced by one college of nursing in developing such a scheme are explored. PMID- 1513300 TI - An integrated approach to curriculum development. AB - This paper explores some aspects of what is meant by integration in a nursing curriculum, by looking at both integration of course content and subject matter, and a consequent move away from separated academic disciplines towards a thematic approach, and at integration of the student group, so that different groups of nurse learners study and learn together for a certain proportion of the programme. We consider reasons for adopting an integrated approach by discussion: issues related to learners and the learning context (these include theories of how adults learn and our perspective on the part to be played by experiential learning); the potential implications for client/patient care and the need for transferable skills to work as a member of a team; and staff development for the teachers, including moves away from possible isolation towards team-teaching. We then go on to describe a model for curriculum development devised in our own institution and based on these principles, which incorporates the development of learners professionally, educationally and personally. This paper discusses the topic from a mainly theoretical perspective, and many of the issues will be relevant to a wide range of courses. PMID- 1513299 TI - Tutorials in nurse education: a survey of its use in district nursing training. AB - This paper reports the findings of a survey of registered nurses undertaking the district nurse training. District nurse students were asked their views of tutorial arrangements, methods used, their effectiveness and their perceptions of the role that tutorials play in the learning process. A questionnaire was sent to 60 course tutors in five institutions within the South West Regional Health Authority area; 51 were returned completed. The results suggest that tutorial arrangements in courses preparing district nurses need to be re-examined in the light of comments from this group of students. PMID- 1513301 TI - Extension of the raccoon rabies epizootic--United States, 1992. AB - Raccoon rabies, epizootic among raccoons in the southeastern and mid-Atlantic states, has become an increasingly important problem in the northeastern United States. The extension of the epizootic was largely responsible for the 43% increase in the total number of reported cases of animal rabies in the United States from 1990 (4881) to 1991 (6975). In 1991, 3079 cases of rabies in raccoons were reported, the largest number reported in the history of animal surveillance in the United States. This report summarizes the extension of the epizootic into six additional states since 1989. PMID- 1513302 TI - Cholera associated with international travel, 1992. AB - Approximately one case of cholera per week is being reported in the United States. Most of these cases have been acquired during international travel and involve persons who return to their homelands to visit family or foreign nationals visiting relatives in the United States. This report summarizes case reports from four states during 1992. PMID- 1513303 TI - Cholesterol screening and awareness--behavioral risk factor surveillance system, 1990. AB - The association between high blood cholesterol and coronary heart disease (CHD) has been well documented (1), and lowering total and low-density lipoprotein cholesterol levels can reduce the incidence of CHD. For example, a 1% decrease in serum cholesterol can result in a 2% decrease in the risk for CHD (2). To reduce the prevalence of high blood cholesterol in the United States, the National Heart, Lung, and Blood Institute initiated the National Cholesterol Education Program (NCEP) in 1985 (3) to encourage all adults to have their cholesterol levels checked at least once every 5 years, know their cholesterol levels, and if it is elevated, take steps to lower their levels. This report summarizes data on the proportion of adults who have been screened and report knowing their cholesterol levels. PMID- 1513304 TI - Seroconversion to simian immunodeficiency virus in two laboratory workers. AB - Simian immunodeficiency viruses (SIVs) are lentiviruses that cause acquired immunodeficiency syndrome (AIDS)-like illnesses in susceptible macaque monkeys and are used in the study of AIDS (1). In November 1988, CDC published guidelines to minimize the risk of SIV transmission to research laboratory workers (2). This report summarizes the investigation of two laboratory workers who seroconverted following occupational exposures to SIV. PMID- 1513305 TI - [The experiment and clinical evaluation of chemosensitivity test for esophageal and gastric cancer by ATP assay using endoscopic biopsy]. AB - The chemosensitivity test for esophageal and gastric cancer cells collected by endoscopic biopsies before operation was investigated for evaluation by ATP assay. Experimentally, ATP assay was applied in human esophageal and gastric cancer cell line transplanted in nude mice. ATP level was measured by Lumiphotometer and showed positive linear correlation with the number of cancer cells in more than 10(3). Also ATP level increased when more than 10(3) cancer cells were cultured for more than 48 hours. On the other hand, more than 10(3) cancer cells were indicated to be collected by endoscopic biopsies, experimentally. Clinically, 7 specimens collected by endoscopic biopsy and 5 anticancer agents (MMC, CDDP, 5-FU, ADM and BLM) were used for the test. Forty nine cases, 31 cases of esophageal cancer and 18 cases of gastric cancer were subjected to the study. The evaluability rates were 93.8%, respectively. Over-all predictive accuracy for esophageal cancer between the clinical responses and results of the assay was 72.0%. These results suggested the usefulness of biopsy specimens for the chemosensitivity test of anticancer agents. PMID- 1513306 TI - [Clinical study of 76 cases of smooth muscle tumor of the stomach]. AB - Seventy six patients with smooth muscle tumor of the stomach (18 leiomyoma, 58 leiomyosarcoma) operated at Cancer Institute Hospital are presented. 1) Advanced age, short duration of illness, region of the middle portion of the stomach, large tumor size and ulcerative tumor were suggestive of pathological malignancy. 2) Male, symptomatic and larger tumor size were suggestive of poor prognosis. 3) The rate of curative surgery was 94.8% for fifty eight patients with leiomyosarcoma. The cumulative five-year survival rate after curative operation was 74.9% for all patients with leiomyosarcoma. Regardless of resecting method, all patients with tumors less than 5 cm in diameter lived without any indication of recurrence. 4) Four of the 58 patients with leiomyosarcoma had regional lymph node metastasis and died at less than 5 years following operation. PMID- 1513307 TI - [A scanning electron microscopic study on experimental ischemic lesions in dogs]. AB - Occlusion of minute vessels in the bowel wall is thought to be a cause of ischemic lesions. This study was performed to clarify the pathohistology and the morphology of these various lesions. Microbarium suspension was injected into the mesenteric vessels of twenty four dogs and the ischemic lesions were produced experimentally. The degree of the bowel damage was parallel to the amount of injected microbarium suspension. The resected specimen of the various stages of the disease was studied histologically and morphologically by a scanning electron microscopy. With the small amount of barium suspension the lesions were confined to the mucosal layers. The epithelial cells regenerated regularly and the villi normalized rather quickly, and these lesions healed within one to two weeks (transient form). With the large amount of barium suspension the lesions involved both submucosal and muscular layers. The epithelial cells regenerated irregularly and the villi rearranged to abnormal forms. These lesions healed in two to four weeks leaving the stenosis due to scar formation (stricturing form). This study suggests that scanning electron microscopic investigation can be used to assess the details of morphological changes of ischemic mucosa, special reference to the degeneration and regeneration process of epithelium of the villi. PMID- 1513308 TI - [Radioimmunodetection of colorectal cancer, using anti-CEA monoclonal antibody CEA 102: whole IgG versus F(ab')2 fragments]. AB - In order to improve cancer imaging with radiolabeled antibodies, three factors appeared to be of particular importance: (1) The selection of the most favorable monoclonal antibody directed to tumor-associated antigen. (2) The use of F(ab')2 or Fab fragments. (3) Selection of the most convenient isotope. Monoclonal antibody CEA 102 was produced by immunization by purified CEA, and its F(ab')2 fragments were compared with whole IgG as a radiotracer for radioimmunodetection of the colorectal cancer. Fragments were eliminated from the circulation twice as fast as whole IgG, and tumor-to-background ratio was achieved more than 1 at 2-3 days with F(ab')2, but 6-7 days with whole IgG in tumor bearing nude mice. In clinical study, F(ab')2 demonstrated clear image on the 1 at day after injection, whereas achievement of the image was possible on the 3rd day in whole IgG. These results indicated that fragments are preferred over whole IgG. Therefore fragments make it possible to preclude dual isotope subtraction methods, and omit the long delays before imaging. They also make it possible to use short half life radionuclides with excellent photon properties, such as 123I and 99mTc. PMID- 1513309 TI - [Effect of prostaglandin E1 derivative on labilization of liver lysosomal membrane in partial liver ischemia]. AB - The change of liver lysosomal enzymes in tissue and serum during a reperfusion period was studied in partial liver ischemic model in rats and effect of Prostaglandin E1 (PGE1) derivative on partial liver ischemia was investigated. Partial liver ischemia was induced by clamping the branches of the vessels to the right and caudate lobes of rat liver. The clamp was released after 30 minutes of ischemia. Ischemic and nonischemic lobes of the liver were separately removed and the serum was also collected immediately and two hours after the release of the clamp. Lysosomal enzyme activities from free and bound lysosomal fraction were measured separately and the fragility index (F.I.) was calculated. PGE1 derivative was administered intraperitoneally 24, 6, 0.5 hours prior to the induction of ischemia at each dose of 0.05 microgram/kg. Pretreatment with PGE1 derivative prevented lysosomal labilization in ischemic lobe, since there was a significant decrease in F.I. of cathepsin D in the PGE1-pretreated group (preischemia; 28.3 +/- 2.4%, immediately after reperfusion; 30.3 +/- 2.5%, two hours after reperfusion; 30.3 +/- 2.5%) compared to the placebo group (immediately after reperfusion; 40.9 +/- 3.4%, two hours after reperfusion; 41.7 +/- 3.4%, p less than 0.05, p less than 0.05, p less than 0.01, respectively). Pretreatment with PGE1 derivative also significantly suppressed the increase of serum lysosomal enzyme activity. These results showed that PGE1 derivative improved liver lysosomal labilization in partial liver ischemia. PMID- 1513310 TI - [Prognostic significance of internal mammary lymph node metastases in breast cancer patients]. AB - Examination was made of clinical, histological and biological prognostic factors in 207 patients with invasive breast cancer, and determination was made as to whether variable prognostic factors, especially internal mammary lymph node metastases, would serve as a basis for the prognosis of breast cancer. In a univariate study, overall survival was significantly corrected with tumor size, axillary lymph node status, axillary and internal mammary lymph node metastases and DNA ploidy status. In a multivariate study, however, only axillary and internal mammary lymph node metastases were recognized as important, and independent prognostic factors on survival. Neither axillary lymph node status nor DNA ploidy status appeared an important prognostic factor. Axillary and internal mammary lymph node metastases could not be predicted from their clinical assessment. Only axillary lymph node dissection and biopsy of first and second intercostal spaces were concluded to be useful for accurately indicating the status of these lymph nodes. PMID- 1513311 TI - [The effect of prostacyclin (PGI) on denervated tissues--especially, about denervation supersensitivity]. AB - It is well known that contractive agents of smooth muscle have denervation supersensitivity. But, the existence of denervation supersensitivity in relaxed ones does not become so clear. We investigated these supersensitivity, especially prostacyclin (PGI2). We made the denervated artery by lumbar sympathetic ganglionectomy in mongrel dogs. Namely, saphenous and dorsal pedal arteries were denervated by this ganglionectomy. And we studied the changes of these arterial tensions by magnus apparatus. Dose-response (D-R) curves of denervated arteries for KCl and noradrenaline (NE) shifted to left against control arteries. Next, we studied effects of PGI2. At first, we measured ED50 of KCl and NE contraction. And, we produced the half contraction on each artery by using ED50 of KCl and NE. Lastly, PGI2 was added on the half contractive arteries to study relaxed changes. D-R curves of denervated arteries for PGI2 shifted to left, too. These denervated arteries acquired the supersensitivity for PGI2. Clinically, if we use relaxants after organ transplantation, these drugs may be very effective for the perfusion of the grafts. PMID- 1513312 TI - [Angioscopic prediction of late vascular patency after transluminal balloon angioplasty for arteriosclerotic obstructions of the artery of the lower extremities]. AB - Arterial occlusion or stenosis of the lower extremity due to arteriosclerosis obliterans (ASO) was treated by transluminal balloon angioplasty (TBA). Angioscopic observation of the vascular lumen, performed immediately after TBA, provided five major findings: (1) abrasion of the intima, (2) irregularity of the lumen due to poor expansion, (3) laceration of the wall, (4) mural thrombus and (5) calcification. The degree of each of these abnormalities was scored with a 3 grade scale (0, 1 and 2), and scores for the 5 abnormalities were totaled in each patient. Analysis of the relationship between scores and postoperative vascular patency demonstrated that patients without vascular patency in the early (within 6 months) or late period (6 months or more) after the operation had higher total scores as compared to those in whom the vessel remained patient in the corresponding postoperative periods (p less than 0.01, p less than 0.05). Among others, patients with a total score over 5 showed markedly lower patency rates in the early period (10%) as well as late period (0%) after the operation (p less than 0.01). These results indicate the usefulness of post-TBA angioscopic observation of vascular lumen in predicting the long-term patency of the vessels operated on. PMID- 1513313 TI - [Effects of surgical stress on peripheral venous functions]. AB - Postoperative changes in peripheral venous functions were determined by Ga-In strain gauge plethysmography in 28 surgical patients, and central venous functions and urine catecholamine levels were also measured. The results were as follows: 1. The maximum venous outflow (MVO) and arterial blood inflow volume (AF) of the healthy arms tended to increase with age, but showed no sex or right to-left difference. 2. MVO, AF and venous distensibility were decreased postoperatively, and the decreases were greater in the patients with major surgery than in those with minor surgery. 3. MVO in the patients with high urine levels of adrenaline and noradrenaline showed a greater decrease than those in normal subjects, and the majority of these patients were found to have had major surgery. There was a negative correlation between the urine noradrenaline level and MVO. 4. The decrease in peripheral venous functions preceded the decrease in central venous functions. 5. The postoperative decrease in peripheral venous functions was considered to be the result of active vasoconstriction due to hypersecretion of catecholamines caused by surgical stress and increase in the extravascular pressure. 6. Measurement of venous functions of the arm may be a good parameter for detecting circulatory disturbances due to surgical stress. PMID- 1513314 TI - [99mTC-HSA lymphoscintigraphy and leg edema after arterial reconstruction]. AB - To investigate the etiology of lower limb edema after arterial reconstruction, 12 patients (16 limbs) who underwent arterial reconstruction due to atherosclerosis obliterans were observed. There was no relationship between the severity of limb edema and serum factors (serum total protein, albumin, BUN and creatinine), ankle/brachial arterial pressure ratio, peripheral venous pressure or RI lymphoscintigraphy in the supine position. The lymphatic flow in RI lymphoscintigraphy at 3-4 weeks after operation increased with statistically significant difference compared to the preoperative flow whether the patient was in the supine or upright position. Though there was no significant relationship between the severity of leg edema and postoperative lymphatic flow in the supine position, postoperative lymphatic flow in the upright position decreased as the severity of leg edema increased. Increased lymphatic flow in the follow-up period was associated with increased severity of leg edema in the upright position. It is concluded that postoperative leg edema is due to the damage to the lymphatic vessels during operation, and then the lymphatic channels cannot adapt to the increased lymphatic flow after the arterial reconstruction. PMID- 1513315 TI - [Liposarcoma of the transverse mesocolon--a case report]. AB - Primary mesenteric liposarcoma is a rare neoplasm. We experienced a case of liposarcoma of transverse mesocolon. In our case, the examination of ultrasonography and CT scan revealed the tumor was solid and encapsulated. Preoperatively we suspected the tumor was malignant by the angiographic findings. Laparotomy revealed that the tumor was located in the transverse mesocolon and it could be removed easily. The histopathological diagnosis was myxoid type liposarcoma. It is said generally that liposarcoma is liable to recur after simple resection, therefore, we reconsider that we should have excised more extensively for this case. The patient is doing well without evidence of recurrence for 17 months after operation. PMID- 1513316 TI - [A case report of aneurysm in the root of splenic artery of the spleno-mesenteric type treated with reanastomosis]. AB - A 76-year-old woman with lumbo-abdominal pain as a chief complaint went through a series of examinations including ultrasonography, CT, and angiography, the final diagnosis being aneurysm of the splenic artery congenitally arising from the superior mesenteric artery (SMA). Since the SMA had to be clamped during the excision of the aneurysm, a biballoon intraluminal shunting was utilized to avoid the visceral ischemia. The splenic artery distal to the aneurysm then underwent end-to-side anastomosis to the SMA. This shunting procedure was considered convenient and applicable to other similar situations in the vascular surgery. PMID- 1513317 TI - [Alteration in DNA ploidy in the gastric stump mucosa: preliminary report]. PMID- 1513318 TI - [Inhibitory effect of urinary trypsin inhibitor on the increase in circulating IL 6 levels during abdominal surgery: preliminary report]. PMID- 1513319 TI - [Splenectomy protect the mice from cachectic death (preliminary study): preliminary report]. PMID- 1513320 TI - Human gene S31 encodes the pharmacologically defined serotonin 5 hydroxytryptamine1E receptor. AB - The gene encoding a human 5-hydroxytryptamine (5-HT)1 receptor subtype was isolated from a human placental genomic library by using oligonucleotide probes derived from transmembrane regions of the cloned human 5-HT1D beta receptor. The deduced amino acid sequence of the genomic clone hp75d is identical to that of the recently isolated, but uncharacterized, novel serotonin receptor gene S31. Transmembrane domain sequence comparison of clone hp75d with other guanine nucleotide-binding protein-coupled receptors revealed the highest degree of homology (64%) to the 5-HT1D alpha and 5-HT1D beta subtypes and lower degrees of homology (35-52%) to other serotonergic and catecholaminergic receptors. A stable cell line expressing this gene was established, using murine fibroblasts as the host cell, for pharmacological evaluation. High affinity (Kd = 9.7 nM), saturable (Bmax = 2.4 pmol/mg of protein) [3H]5-HT binding was detected using membranes derived from stable transfectants. Most compounds displayed low affinity (K(i) greater than 200 nM) for the expressed gene, with the exception of 5-HT (K(i) = 10 nM). The rank order of potency of ligands to compete for the [3H]5-HT-labeled site best matched the binding profile of the pharmacologically defined 5-HT1E binding site, 5-HT greater than methysergide greater than ergotamine greater than 8-hydroxy-2-(di-n-propylamino)tetralin greater than 5-carboxyamidotryptamine greater than ketanserin. 5'-Guanylylimidodiphosphate decreased high affinity agonist ([3H]5-HT) binding in a dose-dependent manner. 5-HT produced a dose dependent inhibition of forskolin-stimulated cAMP accumulation in intact cells stably expressing the 5-HT1E gene. The response was blocked by the nonselective 5 HT1 receptor antagonist methiothepin. The molecular biological and pharmacological data are consistent with the designation that clone hp75d encodes a functional 5-HT1E receptor. PMID- 1513321 TI - Association of solubilized angiotensin II receptors with phospholipase C-alpha in murine neuroblastoma NIE-115 cells. AB - The peptide angiotensin II (AngII) has been reported to stimulate phosphoinositide-specific phospholipase C (PLC) activity in the murine neuroblastoma cell line N1E-115. In the present study, polyclonal antibodies raised against a PLC isoenzyme, PLC-alpha, reacted with a 60-kDa protein present in both membrane and cytosolic fractions of differentiated N1E-115 cells. In order to examine the possible association of PLC-alpha with cell surface AngII receptors (AngII-Rs), membranes from differentiated N1E-115 cells were solubilized, using the zwitterionic detergent 3-[(3 cholamidopropyl)dimethylammonio]-1-propanesulfonate (CHAPS). CHAPS (1%) solubilized AngII-Rs, from N1E-115 cells, that maintained their high affinity for agonists. Gel filtration analysis of the solubilized membranes revealed that the majority of the specific binding of 125I-AngII eluted as a large protein complex with a molecular mass of 380 kDa and that agonist binding was partially reduced by guanosine-5'-O-(3-thio)triphosphate (GTP gamma S), within this complex. CHAPS also effectively solubilized immunoreactive PLC-alpha, from N1E-115 cell membranes, that was similarly present within the 380-kDa AngII-binding complex. Anti-PLC-alpha antisera immunoprecipitated approximately 16% of the total phosphatidylinositol-4,5-bisphosphate-specific PLC activity in the 1% CHAPS extract and 40% of cytosolic PLC activity. Moreover, a 60-kDa 35S-Trans S-labeled protein, comigrating with immunoreactive PLC-alpha, was immunoprecipitated from the 1% CHAPS extract by the antisera. In addition, anti-PLC-alpha antisera immunoprecipitated approximately 20% of solubilized AngII-Rs prebound with 125I AngII but failed to precipitate receptors prebound with the antagonist 125I Sarc1,Ile8-AngII. The anti-PLC-alpha antisera also immunoprecipitated AngII-Rs when intact membranes were labeled with 125I-AngII before solubilization in 1% CHAPS, suggesting that the AngII-R interaction with PLC-alpha was not the result of detergent-promoted protein-protein interaction. On the other hand, monoclonal antibodies against another PLC isozyme, PLC-gamma, did not precipitate AngII-Rs in solubilized N1E-115 membranes. Finally, the formation of the immunoprecipitated AngII-R-PLC-alpha complex was disrupted by the nonhydrolyzable guanine nucleotide analog GTP gamma S, suggesting that the interaction between AngII-Rs and PLC-alpha is likely to involve a heterotrimeric guanine nucleotide binding protein in neuron-like cells. PMID- 1513322 TI - Null phenotype for cytochrome P450 2B2 in the rat results from a deletion of its structural gene. AB - The absence of phenobarbital (PB)-inducible cytochrome P450 2B2 (CYP2B2) in hepatic microsomes from Marshall 520 (M520) and Wistar Munich (WM) inbred strains of rat was previously reported [Biochem. Genet. 25:527-534 (1987)], and it was subsequently shown for M520 rats that corresponding CYP2B2 mRNA was not detected in hepatic extracts from either control or PB-treated animals [DNA 8:29-37 (1989)]. In the present study, solution hybridization was used to quantify PB induced CYP2B2 and CYP2B1 mRNAs in livers from M520, WM, and outbred Sprague Dawley rats, as well as additional inbred strains that express all known electrophoretic phenotypes for both of these closely related isozymes. Amounts of these mRNAs were also measured for F1 and F2 progenies of crosses involving M520 rats. The results indicated that the extent of PB induction of both isozymes appears to be independent of the electrophoretic phenotype. It was also shown that the null phenotype for CYP2B2 observed in M520 rats results from a mutation of a single autosomal gene and is inherited codominantly, regarding protein and mRNA phenotypes. Analyses of restriction digests and specific polymerase chain reaction products of hepatic DNAs revealed that the basis for the null phenotype of CYP2B2 in M520 and WM rats was a deletion of the CYP2B2 gene. PMID- 1513323 TI - Sequence analysis, in vitro translation, and expression of the cDNA for rat liver minoxidil sulfotransferase. AB - A cDNA encoding minoxidil sulfotransferase (Mx-ST), a rat liver cytosolic sulfotransferase that catalyzes the 3'-phosphoadenosine 5'-phosphosulfate dependent sulfate conjugation of minoxidil and p-nitrophenol, has been isolated from a lambda gt11 cDNA library constructed from poly(A)+ RNA isolated from female Sprague-Dawley rat liver. The largest cDNA, designated Mx-STb, consists of 1245 base pairs and contains an open reading frame of 291 amino acids. The predicted size of the protein translated by Mx-STb is 33,909 Da; however, the molecular mass of the pure protein [Biochem. J. 270:721-728 (1990)] is estimated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis to be 35,000 Da. The size of the protein obtained by in vitro translation of Mx-STb is identical to that of the pure protein. Results of initial studies of the expression of Mx-STb in COS-1 cells indicate that the expressed protein displays characteristic Mx-ST and p-nitrophenol sulfotransferase activity, is recognized by rabbit polyclonal antibodies raised against pure rat liver Mx-ST, and migrates at approximately 35,000 Da during sodium dodecyl sulfate-polyacrylamide gel electrophoresis. This paper presents the cloning and expression of a rat phenol sulfotransferase for which the physical, immunological, and kinetic properties are known. Isolation of the cDNA for Mx-ST will aid in the investigation of the heterogeneity, the tissue localization, and the characterization of the kinetic properties of this important drug-metabolizing enzyme, with respect to other similar phenol sulfotransferases present in rat liver cytosol. PMID- 1513324 TI - Cloned mouse N-acetyltransferases: enzymatic properties of expressed Nat-1 and Nat-2 gene products. AB - N-Acetylation plays an important role in the metabolism of a wide variety of hydrazine drugs and arylamine drugs and carcinogens. Humans have genetically determined differences in their N-acetyltransferase activities and are phenotypically classified as rapid or slow acetylators. Mice have a similar genetic polymorphism in N-acetyltransferase activity and have been used as models of the human polymorphism in many studies of the toxicology and carcinogenicity of arylamines. Recently, two N-acetyltransferase genes, Nat-1 and Nat-2, were cloned from rapid (C57BL/6J) and slow (A/J) acetylator mouse strains. The genomic clone encoding NAT-1 is identical in rapid and slow acetylator mouse strains, whereas the clone encoding NAT-2 differs between rapid and slow strains by a single base pair, which changes the encoded amino acid from Asn99 in the rapid acetylator strain to Ile99 in the slow acetylator strain. In this report, the N acetylation polymorphism in mice was investigated by transiently expressing the cloned N-acetyltransferase genes in COS-1 cells. The intronless coding regions of Nat-1 and Nat-2 showed different substrate specificities; isoniazid was a preferred substrate for NAT-1, whereas p-aminobenzoic acid was preferred for NAT 2(99asn) and NAT-2(99ile). All three enzymes acetylated 2-aminofluorene, but none of them acetylated sulfamethazine. Kinetic constants determined for the expressed enzymes with 2-aminofluorene and p-aminobenzoic acid indicated that Km values were not significantly different between the enzymes, although the Vmax value of NAT-2(99asn) was consistently 2-3-fold higher than that of NAT-1 or NAT-2(99ile). Nat-1 and Nat-2 encoded mRNAs of approximately 1.4 kilobases in livers of rapid and slow acetylators. Nat-2 mRNA was more abundant in liver than Nat-1 mRNA. The abundance of Nat-2 mRNA and Nat-1 mRNA was equivalent in both rapid and slow acetylator mouse strain livers. Incubation of transfected COS-1 cell cytosols at 37 degrees showed that the time for decline of NAT activity to 50% of its initial value was 45 hr for NAT-1, 60 hr for NAT-2(99asn), and 4 hr for NAT-2(99ile). This 15-fold difference in the heat stability of the rapid and slow isoforms of NAT activity was also observed in cytosols from rapid and slow acetylator livers. Comparison of the rates of translation of the rapid and slow isoforms of NAT-2 in an in vitro system showed that NAT-2(99asn) was translated at approximately twice the rate of NAT-2(99ile).(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1513325 TI - Transcriptional regulation of rat microsomal epoxide hydrolase gene by imidazole antimycotic agents. AB - The effects of imidazole antifungal agents, including ketoconazole, clotrimazole, miconazole, and econazole, on the expression and regulation of microsomal epoxide hydrolase (mEH) were examined in rat hepatic tissue (doses of agents, 150 mg/kg of body weight/day, orally). Immunoblot analyses revealed that administration of either ketoconazole or clotrimazole caused a approximately 4-5-fold increase in mEH levels, whereas either miconazole or econazole resulted in a approximately 7 fold increase in mEH at day 3 after treatment. RNA hybridization analyses, probed with a 1.3-kilobase mEH cDNA, revealed that administration of these imidazole antifungal agents caused substantial elevation of hepatic mEH mRNA in total RNA. Hepatic mEH mRNA levels in total RNA were elevated approximately 11-, 15-, and 18 fold at 12, 24, and 72 hr, respectively, after ketoconazole treatment, whereas mEH mRNA levels were increased approximately 14-, 19-, and 22-fold, respectively, relative to control, at the same time points after clotrimazole treatment. The rate of increase of mEH mRNA caused by miconazole was more rapid than the rates observed for the other agents examined, with a maximal increase in mRNA being noted at 12 hr after treatment. The degree of mEH mRNA increase after 3 consecutive days of miconazole treatment was appreciably less than that observed at 12 hr after a single treatment. Econazole caused a maximal increase at 24 hr and subsequent decline in mEH mRNA levels after 3 consecutive days of treatment. Elevation of mEH mRNA levels by these antimycotic agents was confirmed in poly(A)+ RNA, as assessed by both Northern and slot blot hybridization analyses. Nuclear run-on analyses revealed that administration of ketoconazole, clotrimazole, or miconazole stimulated the rate of mEH gene transcription at 12 hr after treatment by 11-, 8.5-, and 9-fold, respectively, compared with control, whereas econazole resulted in a 4-fold increase in the rate of mEH gene transcription at the same time point. The transcription rates of mEH mRNA at 24 hr were significantly less than those observed at 12 hr after a single treatment with either ketoconazole, miconazole, or econazole, resulting in 6.5-, 2.5-, and 2-fold increases, respectively, relative to control. Clotrimazole, however, maintained the activated mEH transcription rate at 24 hr after treatment, exhibiting a 11-fold increase, compared with control. These results provide evidence that the imidazole antimycotic agents induce mEH and that the mEH induction involves large increases in mRNA, with transcriptional activation. PMID- 1513326 TI - Anti-liver microsomes autoantibodies and dihydralazine-induced hepatitis: specificity of autoantibodies and inductive capacity of the drug. AB - Anti-liver microsomes (anti-LM) autoantibodies in patients with dihydralazine induced hepatitis were found to react specifically with cytochrome P4501A2 (P4501A2) but not with P4501A1 expressed in yeast and bacteria. These results were confirmed by immunoinhibition of methoxyresorufin-O-demethylase activity (supported by the P4501A subfamily); anti-LM antibodies more strongly inhibited this activity in yeast expressing P4501A2 than in yeast expressing P4501A1. Anti LM were shown to be specific to the disease; in three cases, these autoantibodies were present at high titers during disease, whereas the titers decreased upon recovery and became undetectable a few months after recovery. Thus, there exists a time-dependent relationship between the disease and the autoantibodies, which does not prove that the autoantibodies are causative of the hepatitis; they might only be a marker. The inductive capacity of dihydralazine toward P450 was also studied. In rats treated in vivo and in human hepatocytes treated in vitro with dihydralazine, a 2-fold increase in P4501A2- and P4501A-supported monooxygenase activities was found. The levels of the other P450 isoforms tested were unchanged during treatment, both in vivo in rats and in vitro in cultures of human hepatocytes. In human hepatocytes, dihydralazine produced a dose-dependent increase in the level of P4501A up to 0.1 mM; induction of P4501A was less strong at 0.2 mM and disappeared at 0.5 mM. The same treatment did not change the level of P4503A4, taken as control. The strong heterogeneity in the expression of P4501A enzymes in human liver and the capacity of these enzymes for induction by dihydralazine and by other compounds might be predisposing factors in this autoimmune disease. PMID- 1513327 TI - Role of ornithine decarboxylase suppression and polyamine depletion in the antiproliferative activity of polyamine analogs. AB - Two transfected cell lines, one carrying a mammalian ornithine decarboxylase (ODC) that is suppressed by polyamines and one carrying a trypanosomal ODC that is not, were used to ask whether ODC suppression is necessary for the antiproliferative activities of two polyamine analogs, N1,N8-bis(ethyl)spermidine (BES) and N1,N14-bis(ethyl)homospermine (BE444). Both analogs accumulated within cells and suppressed S-adenosylmethionine decarboxylase, as well as polyamine sensitive mouse ODC activity. Neither drug was able to suppress the activity of the polyamine-refractory trypanosome ODC. But, whereas BE444 was able to inhibit growth of both cell lines, BES could inhibit only growth of cells carrying the polyamine-sensitive ODC, under conditions that cause prolonged depletion of endogenous polyamines. We conclude from these studies that the antiproliferative activity of BES, a less potent drug, requires the suppression of ODC. The efficacy of BE444 is enhanced by its ability to suppress ODC. However, it can function without ODC suppression, whereas BES cannot. PMID- 1513328 TI - Evidence for the stereoselective inhibition of chick embryo hepatic ferrochelatase by N-alkylated porphyrins. II. AB - N-Ethylprotoporphyrin (N-ethyl-PP) was isolated from the livers of phenobarbital pretreated rats after the administration of 3,5-diethoxycarbonyl-1,4-dihydro-2,6 dimethyl-4-ethylpyridine, separated into its four regioisomers by high performance liquid chromatography, and quantitated. The percentage ratio, in the chromatogram, of the peak areas of the ring A-substituted (NA) and the ring B substituted (NB) regioisomers was 80:20, compared with 50:50 for synthetic N ethyl-PP. The NA regioisomer of N-ethyl-PP isolated from rat liver was found to be approximately 5 times more potent an inhibitor of ferrochelatase than was the NB regioisomer. Because the synthetic NA regioisomer (an equal mixture of the NA and the epi-NA enantiomers) is equipotent with the synthetic NB regioisomer (an equal mixture of the NB and the epi-NB enantiomers), epi-NB must be more potent than epi-NA. The higher potency previously observed with the NA plus NB regioisomers of N-ethyl-PP isolated from rat liver, compared with the NA plus NB regioisomers of synthetic N-ethyl-PP, is explained by the fact that the biological preparation contains 80% of the potent NA, compared with 25% of the potent NA and 25% of the potent epi-NB in the synthetic preparation. The critical features for optimal ferrochelatase-inhibitory activity are the ring A N-ethyl group facing downward in the NA isomer and the ring B N-ethyl group in the epi-NB isomer being rotated through 180 degrees to occupy the same position. According to one proposed mechanism, N-alkylprotoporphyrins inhibit ferrochelatase by serving as transition state analogues for the iron insertion step. X-ray crystallography shows that the N-alkyl group-bearing pyrrole ring and the pyrrole ring opposite to the N-alkyl group are tilted out of planarity in opposite directions. We suggest that this tilting reflects the normal conformational changes required for the insertion of iron into the protoporphyrin IX ring by ferrochelatase and that the greater inhibitory activity of NA and epi-NB isomers, compared with epi-NA and NB isomers, is due to the fact that the normal mechanism for ferrochelatase-catalyzed iron insertion has preference for an A-C ring tilt over a B-D ring tilt. PMID- 1513329 TI - Complex allosteric modulation of cardiac muscarinic receptors by protamine: potential model for putative endogenous ligands. AB - A large number of diverse pharmacological agents bind to a secondary domain on the muscarinic receptor, to influence allosterically the interaction of ligands at the primary binding site. Based on common structural features of these antagonists, we examined the interaction of protamine, an endogenous polycationic peptide, and of polyamines with muscarinic receptors in rat heart. Our results provide several lines of qualitative evidence that protamine allosterically modulates the conformation of muscarinic receptors, in a marked negatively cooperative manner. It decelerated the dissociation of N-[3H]methylscopolamine ([3H] NMS) initiated by atropine, in a concentration-dependent fashion. Inhibition by protamine of [3H]NMS binding at equilibrium showed a distinct plateau, which increased in magnitude at higher ligand concentrations. Scatchard analysis of saturation isotherms of [3H]NMS binding in the absence and presence of protamine indicated that protamine did not alter Bmax in a statistically significant fashion, although there was a trend of a concentration-dependent increase in this parameter. On the other hand, it caused a marked concentration dependent decrease in the affinity of [3H]NMS, and this effect reached a ceiling limit. However, there were marked quantitative deviations of the interaction of protamine from a simple ternary allosteric model. Some of these discrepancies could be explained by the tendency of protamine to increase Bmax. The allosteric actions of protamine demonstrated in kinetic and equilibrium experiments were selective for m1 and m2 muscarinic receptors, compared with m3, m4, and m5 receptors, as studied in Chinese hamster ovary cells transfected with the genes of the different muscarinic receptors. Arginine residues play an important role in the allosteric interaction of protamine, inasmuch as poly-L-arginine qualitatively mimicked the effects of protamine. In contrast, no effects of the polyamines spermine, spermidine, and putrescine were observed on [3H]NMS binding. This is the first report on the allosteric modulation of muscarinic receptors by an endogenous peptide. PMID- 1513331 TI - Anomeric preference of glucose utilization in rat erythrocytes. AB - The beta-anomer of glucose relative to the alpha-anomer was more rapidly metabolized into lactate by rat erythrocytes at 37 degrees C (beta/alpha ratio = ca. 1.3): the amounts of alpha- and beta-D-glucose metabolized into lactate during 3 min were 0.21 and 0.27 mumol/gHb, respectively. Also, the transport of beta-D-glucose into erythrocytes was more rapid than that of alpha-D-glucose: the amounts of alpha- and beta-D-glucose transported into erythrocytes during 3 min were approximately 3.5 and 5.0 mumol/gHb, respectively. Glucose phosphorylation by rat erythrocyte hexokinase (i.e., a possible rate-limiting step in glycolysis) occurred at higher velocities with the beta-anomer than with the alpha-anomer (beta/alpha ratio = 1.28). The Km value of hexokinase for either anomer of glucose was 53 microM. The glucose concentrations in erythrocytes incubated with alpha- and beta-D-glucose reached about 1 mM in 1 min, indicating that hexokinase is almost completely saturated with glucose within less than 1 min. The results suggest that glucose phosphorylation and glucose transport are major and minor determinants, respectively, for the anomeric preference of glucose utilization in rat erythrocytes. PMID- 1513330 TI - Calcium binding proteins in the sarcoplasmic/endoplasmic reticulum of muscle and nonmuscle cells. AB - In this paper we review some of the large quantities of information currently available concerning the identification, structure and function of Ca(2+)-binding proteins of endoplasmic and sarcoplasmic reticulum membranes. The review places particular emphasis on identification and discussion of Ca2+ 'storage' proteins in these membranes. We believe that the evidence reviewed here supports the contention that the Ca(2+)-binding capacity of both calsequestrin and calreticulin favor their contribution as the major Ca(2+)-binding proteins of muscle and nonmuscle cells, respectively. Other Ca(2+)-binding proteins discovered in both endoplasmic reticulum and sarcoplasmic reticulum membranes probably contribute to the overall Ca2+ storage capacity of these membrane organelles, and they also play other important functional role such as posttranslational modification of newly synthesized proteins, a cytoskeletal (structural) function, or movement of Ca2+ within the lumen of the sarcoplasmic/endoplasmic reticulum towards the storage sites. PMID- 1513332 TI - Biochemical characterization of Artemia ras p21. AB - The biochemical properties of Artemia ras proteins (p21) have been studied after immunoprecipitation with the monoclonal antibody Y13-259. The ras products bind GTP and GDP, and have GTPase activity. Artemia p21 was unable to hydrolyze Gp4G, although this dinucleotide exhibits high affinity for the protein. Our results demonstrate that the protein(s) recognized by the Y13-259 antibody in this crustacean behave as typical mammalian ras p21s. PMID- 1513333 TI - Peroxidase-promoted oxidation and peroxidation of the serotonergic neurotoxin 5,7 dihydroxytryptamine. A new pathway for its metabolic degradation. AB - Spectral data provide the first evidence that lactoperoxidase, a model enzyme for most mammalian peroxidases, catalyzed the one-electron oxidation and/or peroxidation of 5,7-dihydroxytryptamine. This process correlates with the production of superoxide radicals as is evident from the observed inhibitory effect of superoxide dismutase on product formation. 5,7-Dihydroxytryptamine is a classical peroxidase-oxidase substrate acting as a one-electron donor for enzyme compounds I, II and III. The one-electron peroxidatic oxidation of this serotonergic neurotoxin, responsible for the selective degeneration of central (5 hydroxytryptamine) neurons, is a fast process requiring measurement on the ms time scale. Attention is drawn to the biochemical and toxicological implications, because this fast reaction results in formation of known cell damaging species: free radicals, superoxide radicals and quinoidal products probably involved in the toxic action of 5,7-dihydroxytryptamine. PMID- 1513334 TI - Effects of tumour necrosis factor-alpha (cachectin) on glucose metabolism in the rat. Intestinal absorption and isolated enterocyte metabolism. AB - Intravenous administration of a single dose (20 micrograms) of recombinant tumour necrosis factor-alpha (TNF, cachectin) to rats decreased the rate of intestinal glucose absorption. In vivo, the oxidation of [U-14C]glucose to 14CO2 was significantly increased by the cytokine. In addition, [14C]lipid accumulation from [U-14C]glucose was increased both in liver and brown adipose tissue of the TNF-injected animals. The decrease observed in intestinal glucose absorption was not associated with changes in intestinal metabolism. There was no difference in glucose metabolism by isolated enterocytes from either control or TNF-injected rats whether in the absence or presence of different concentrations of the cytokine in the incubation medium. In contrast, tumour necrosis factor altered the rate of gastric emptying as measured by the gastrointestinal distribution of 3[H]inulin following an intragastric glucose load. These results suggest that the cytokine profoundly alters glucose metabolism by increasing its whole-body oxidation rate and delaying intestinal absorption through a reduced gastric emptying. PMID- 1513335 TI - The association of human coagulation factors VIII, IXa and X with phospholipid vesicles involves both electrostatic and hydrophobic interactions. AB - Blood coagulation factor X (FX) is converted to its active form (FXa) by a membrane bound multi-protein enzyme complex, comprised of factor VIII (FVIII), factor IXa (FIXa) and FX. Characterization of the molecular forces involved in the association of these proteins with phospholipids is crucial to understanding how these proteins bind to the lipid milieux of physiological membranes. In this report, the molecular forces involved in the association of FVIII, FIXa or FX with phospholipid vesicles (PLV) were characterized by ligand affinity chromatographic analyses. Treating FVIII-affinity columns with agents that disrupt electrostatic interactions caused elution of 15.2% of the total bound PLV, while agents that disrupt hydrophobic interactions caused elution of 84.8% of the total bound PLV. These results demonstrate that the association of PLV with FVIII is primarily hydrophobic. In contrast, the association of PLV with FIXa or FX is largely the result of electrostatic forces. This was established by observing that 71.3% and 78.9% of the total bound PLV was eluted from FIXa- and FX-affinity columns, respectively, by agents that disrupt electrostatic interactions. Of the total bound PLV, 28.7% and 21.2% were eluted from FIXa- and FX-affinity columns, respectively, by agents that disrupt hydrophobic interactions. These data demonstrate that hydrophobic forces play a heretofore unrecognized role in the association of PLV with FIXa or FX. PMID- 1513336 TI - Expression of c-myc protooncogene in rat lens cells during development, maturation and reversal of galactose cataracts. AB - It is well established that normal patterns of epithelial cell proliferation and metabolism, and of fiber cell differentiation and maturation are essential for the maintenance of transparency in the ocular lens. Several factors, including exposure to high levels of sugars, have been known to result in the compromise of lens transparency. For example, initiation of lens cell damage by galactose induces lens epithelial cells to proliferate. Elevated levels of c-myc mRNA have usually been correlated with rapid cell growth and increased entry of cells into the S phase. Therefore, changes in c-myc mRNA levels may provide an early indication of the stimulation of lens epithelial cells to proliferate and differentiate, which has been postulated to be an early and important event in response to lens cell injury by galactose. By Northern blot hybridization analysis we quantitated c-myc mRNA levels in the lens capsule epithelia of rats (1) exposed to galactose, and (2) undergoing a partial recovery from the galactose-induced cell damage. At the onset of lens cell damage, we find c-myc mRNA to elevate to 6-fold by 24 hr, and by 48 hr decreases to about 3-fold the normal levels. During recovery, c-myc mRNA continues to be expressed at high levels approaching a 10-fold increase by day 12, then decreasing to levels of about 8-fold the control by day 30. The 24 h transitory elevation in c-myc mRNA in lens epithelial cells is in accord with our previous observations on the 24 h increase in MP26, gamma crystallin and aldose reductase mRNAs following a high influx of galactose. Therefore, the elevation in c-myc mRNA as well suggest that galactose appears to cause lens cells to undergo an early transitory period of gene induction following the exposure of lens cells to galactose. PMID- 1513337 TI - Specific macromolecular interactions between tau and the microtubule system. AB - The microtubule-associated protein Tau, a major component of brain microtubules, shares common repeated C-terminal sequences with the high molecular-weight protein MAP-2. It has been shown that tau peptides V187-G204 and V218-G235, representing two main repeats, induced brain tubulin assembly in a concentration dependent fashion. The specific roles of these repeats in the interaction of tau with microtubules, and its antigenic nature were investigated using synthetic tau peptides and site-directed monoclonal antibodies. Tau peptides appeared to compete with MAP-2 incorporation into assembled microtubules. The interactions of the tau fragments with beta-tubulin peptides bearing the tau binding domain on tubulin were analyzed by fluorescence spectroscopy. The specificity of the binding was further demonstrated by the reactivity of tau and the tau peptides with a monoclonal anti-idiotypic antibody produced after immunization with the beta-II(422-434) tubulin peptide, as assessed by enzyme-linked immunoassay. Western blots confirmed the interaction of tau with the monoclonal antibody. In addition, immunoassays revealed a competition between the MAP-reacting monoclonal antibody and the tubulin peptide beta-II(422-434) for their interaction with the tau molecule. PMID- 1513338 TI - Calcium-binding protein regucalcin increases calcium-independent proteolytic activity in rat liver cytosol. AB - The effect of regucalcin, isolated from rat liver cytosol, on neutral proteolytic activity in the hepatic cytosol was investigated. The Ca(2+)-requiring proteinase required 5-10 microM Ca2+ for maximal activity in the presence of a protein substrate (globin). The proteinase activity was markedly elevated by the addition of regucalcin (0.25-2.0 microM) in the absence or presence of Ca2+ (5.0 microM) added. The effect of regucalcin, however, was the greater in the absence of Ca2+ than that in the presence. The pronounced effect of regucalcin on the proteinase activity was also seen in the presence of 1.0 mM EGTA with or without Ca2+ (5.0 microM). In the absence of Ca2+, the regucalcin-increased proteinase activity was clearly inhibited by the presence of anti-regucalcin antiserum (diluted to 240 fold), leupeptin (20 and 200 micrograms/ml), and heavy metals (25 microM cadmium or 25 microM zinc), although the inhibition was not complete at the concentration used. The present findings suggest that regucalcin increases proteolytic activity in rat liver cytosol, and that regucalcin may activate Ca(2+)-independent neutral cysteinyl-proteinase. PMID- 1513339 TI - Identification of toxigenic Clostridium difficile strains using a toxin B gene specific oligonucleotide probe. AB - We describe the use of a new specific synthetic oligonucleotide probe, deduced from the sequence of the gene for Clostridium difficile toxin B, to identify toxigenic strains of C. difficile. This probe does not hybridize to the DNA of non-toxigenic strains of C. difficile nor to DNA isolated from different Clostridium species, including C. sordellii. None of the enteric pathogenic bacteria tested were seen to hybridize with the probe. A preliminary study of direct probing of faecal specimens indicates a potential for the use of this DNA probe in the clinical laboratory for the rapid identification of toxigenic strains of C. difficile. PMID- 1513340 TI - Quantification of the detection of Pneumocystis carinii by DNA amplification. AB - We have developed a highly specific and sensitive technique for the detection of Pneumocystis carinii DNA using DNA amplification by the polymerase chain reaction (PCR). PCR products are detected by agarose gel electrophoresis and Southern hybridization to an oligonucleotide probe. Here we report the calibration of parasite numbers with amplification and hybridization signals and show that we can detect P. carinii to a lower limit of one to two organisms. The quantification of this diagnostic technique allows us to establish the number of organisms in a clinical sample which correspond to pneumocystis pneumonia or to sub-clinical pulmonary colonization. PMID- 1513341 TI - Development of cell surface protein associated gene probe specific for Listeria monocytogenes and detection of the bacteria in food by PCR. AB - A genomic library of L. monocytogenes was constructed using lambda Zap II-Eco RI and screened with a monoclonal antibody which is specific for a Listeria cell surface protein. Three positive clones each contained a 6.5 kb insert which in E. coli could express the same Listeria protein. The 6.5 kb insert was further digested with Hin dIII and the smaller fragments were subcloned into a plasmid vector (pBluescript) and screened with 32P-labelled genomic DNA from L. monocytogenes or L. innocua. Three clones which were positive with L. monocytogenes and negative with L. innocua were screened and each contained a 2.1 kb insert. The 2.1 kb insert was partly sequenced and some candidate oligomer probes from the sequences were selected and compared with sequences in a Genbank computer search. One such oligomer probe (T7-list) was confirmed to be specific for L. monocytogenes. The probe hybridized with all 28 strains of L. monocytogenes tested, but not with any of six other Listeria species nor 11 other bacteria tested. Using this probe-primer, a PCR method was developed which could detect as few as 2 cfu of L. monocytogenes in pure cultures, and as few as 4-10 cfu of L. monocytogenes when inoculated into foods. PMID- 1513342 TI - Detection of rabies virus mRNA in mouse brain by using in situ hybridization with digoxigenin-labelled RNA probes. AB - A non-isotopic method of in situ hybridization (ISH) was developed for the detection of rabies virus RNA in paraffin-embedded tissues. Digoxigenin-labelled RNA probes for rabies virus glycoprotein mRNA were used. The method had good sensitivity and low backgrounds, and there was excellent cellular localization of signals. ISH wih digoxigenin-labelled probes was compared with ISH with 3H labelled probes. This non-isotopic method of ISH is more convenient than the radiolabelled method, and it is quicker because a long autoradiographic exposure is not required. PMID- 1513343 TI - Detection of Pneumocystis carinii in a rat model of infection by polymerase chain reaction. AB - The polymerase chain reaction (PCR) was employed to detect Pneumocystis carinii in organs of infected rats. Using a pair of oligonucleotides designed to the dihydrofolate reductase (DHFR) gene of rat P. carinii, specific amplification of an expected 415 bp region of P. carinii DHFR DNA of this organism was achieved, while no amplification occurred with the human, Candida albicans, and Mycobacterium avium and tuberculosis DNAs. Using rat P. carinii isolated from in vitro cultures and infected lung homogenates, the minimum detection level by PCR on an ethidium bromide gel was about 200 organisms and by Southern analysis with radiolabelled DHFR probe the detection level improved to 20 organisms. This level of sensitivity is sufficient to detect P. carinii specific band on the gel in infected rat lung and other organs. This PCR technique is potentially useful for detecting P. carinii in bronchoalveolar lavage (BAL) fluids of AIDS patients and for quantifying the organisms in tissues and in in vitro cultures where a high background with conventional stains makes it harder to determine the number of organisms. PMID- 1513344 TI - Polymerase chain reaction for detection of verocytotoxigenic Escherichia coli isolated from animal and food sources. AB - Animals and their by-products have been implicated as important sources of verocytotoxigenic Escherichia coli (VTEC) associated with disease in humans. VTEC comprise a wide range of serotypes and produce a variety of closely related verocytotoxins (VT). A pair of oligonucleotide primers, targeting conserved sequences found in VT1, VT2 and VTE genes, was used to develop a polymerase chain reaction (PCR) procedure to detect all types of VTEC. Supernatants of boiled broth cultures of VTEC (223 strains) isolated from ground beef, ground pork, raw milk, bovine faeces and porcine faeces; non-VTEC E. coli (72 strains); and other enteric and food bacteria (76 strains) were tested by PCR. The verocytotoxigenicity of these strains was verified by the Vero cell assay. All 223 VTEC isolates, comprising over 50 different serotypes, were detected by the PCR procedure. Shigella dysenteriae type 1 was the only other bacterium that was positive in this assay. As little as 1 pg of VTEC DNA and as few as 17 cfu of VTEC could be detected with this method. The results indicate that these primers detect VTEC over a wide range of serotypes. This method may be applicable as a screening procedure for the detection of VTEC in samples of foods and faeces. PMID- 1513345 TI - Differentiation between pathogenic and non-pathogenic Yersinia enterocolitica strains by colony hybridization with a PCR-mediated digoxigenin-dUTP-labelled probe. AB - The Polymerase Chain Reaction (PCR) method was used to generate a vector-free digoxigenin-dUTP labelled probe that targets the Yersinia enterocolitica gene encoding the heat stable enterotoxin (yst). The probe was used in DNA-DNA colony hybridization to screen 113 strains of Y. enterocolitica and related species for the presence of the enterotoxin gene. In Y. enterocolitica, the probe clearly discriminated between pathogenic and non-pathogenic strains even those belonging to the same serotype. Of the other Yersinia species, only three strains of Y. kristensenii possessed DNA sequences homologous to the yst gene. The probe was further checked for its specificity in artificially inoculated fecal samples and could easily detect the target sequence of the yst gene. The digoxigenin-labelled probe proved to be a reliable epidemiological tool to discriminate between pathogenic and non-pathogenic strains in pure and mixed culture, thus offering the advantage of using a non-radioactive detection system in clinical laboratories with the possibility of reusing the same hybridization solution several times and obtaining results within a relatively short time. PMID- 1513346 TI - Detection of Chlamydia trachomatis by use of polymerase chain reaction. AB - A polymerase chain reaction (PCR) assay was developed for detection of Chlamydia trachomatis DNA. One primer set was used, from the published sequence of the common C. trachomatis plasmid. Detection of amplified sequences was carried out by agarose gel electrophoresis. Analysis of 106 clinical samples tested by cell culture and PCR showed a sensitivity of 100% when PCR was compared with cell culture. PMID- 1513347 TI - DNA probe analysis of diarrhoeagenic Escherichia coli: detection of EAF-positive isolates of traditional enteropathogenic E. coli serotypes among Bangladeshi paediatric diarrhoea patients. AB - Escherichia coli isolates from all surveillance patients less than or equal to 20 months of age seen for diarrhoea at the Dhaka Clinical Treatment Facility of the International Centre for Diarrhoeal Disease Research, Bangladesh between March 1 and August 31, 1988, were collected and hybridized with DNA probes to assess the potential importance of diarrhoeagenic E. coli among paediatric patients in Bangladesh. Of 396 patients evaluated, 18% were infected with enteropathogenic E. coli (EPEC) adherence factor (EAF)-positive E. coli, 23% were infected with enterotoxigenic E. coli (ETEC), 9% were infected with Shiga-like toxin-positive E. coli, and 13% were infected with diffuse adhesiveness-positive E. coli. None were infected with enteroinvasive E. coli. Ten percent of patients were colonized with more than one type of potential diarrhoeagenic E. coli. The majority of EAF positive isolates were of traditional EPEC O:H serotypes. Although this was not a case-control study, the large number of EPEC and ETEC, which are recognized enteric pathogens, suggests these organisms are important causes of diarrhoeal diseases in this pediatric population. PMID- 1513348 TI - Intracranial aneurysms in autosomal dominant polycystic kidney disease. AB - BACKGROUND AND METHODS: Intracranial aneurysms are a feature of autosomal dominant polycystic kidney disease, but their prevalence is uncertain. We studied 92 subjects with autosomal dominant polycystic kidney disease who had no symptoms or signs of any neurologic disorder. To determine the prevalence of intracranial aneurysms, we performed high-resolution computed tomography (CT) in 60 subjects, four-vessel cerebral angiography in 21, and both procedures in 11. RESULTS: Four of the 88 subjects in whom the radiologic studies were successfully completed had intracranial aneurysms (4 percent; 95 percent confidence interval, 0.1 to 9 percent), as compared with the prevalence of 1 percent reported for an angiographic study of the general population. Three of the four subjects had multiple aneurysms. Seven subjects for whom the results of CT studies were suspicious underwent cerebral angiography: two had aneurysms, and five had normal vascular structures that accounted for the suspicious results of tomography. Four subjects who had normal CT imaging studies also had normal angiographic examinations. Eight of the 32 subjects who underwent angiography (25 percent) had transient complications, as compared with 22 of 220 control subjects (10 percent) who did not have polycystic kidney disease (P less than 0.05). We could not identify any risk factor in these subjects that was related to the occurrence of aneurysm. CONCLUSIONS: Asymptomatic intracranial aneurysms appear to be more frequent in people with polycystic kidney disease than in the general population, although our 95 percent confidence interval includes the possibility of no difference. Because cerebral angiography is associated with increased morbidity in people with polycystic kidney disease, we recommend high-resolution CT as a screening test. PMID- 1513349 TI - Does asthma or treatment with theophylline limit children's academic performance? AB - BACKGROUND: Asthma is a major cause of morbidity in childhood, restricting activity and causing absences from school. Theophylline, although effective in managing chronic asthma, has been reported to cause deficits in cognitive functioning and school performance. We therefore examined the effect of asthma and its treatment on academic achievement in a large, representative population of school-age children; matched sibling controls were used for comparison. METHODS: We identified 255 consecutive children with asthma (mean age, 12.0 years) who had taken nationally standardized scholastic achievement tests administered routinely by the schools. One hundred one of these children had siblings without asthma with whom comparisons could be made in reading, mathematics, and a composite measure of achievement. RESULTS: Academic achievement among the children with asthma was similar to normative standards in Iowa and higher than national standards, as reflected in a mean composite T-score of 57.1 (expected mean [+/- SD], 50 +/- 10). For the 101 children with sibling controls, composite T-scores were 58.3 for the children with asthma and 57.5 for the siblings. Eighty-five of these 101 children with asthma were receiving daily maintenance medication for chronic asthma; 72 of these were receiving theophylline. The mean composite T-scores were 58.5 for the theophylline-treated patients and 58.4 for their siblings without asthma. None of the differences between the children with asthma and the sibling controls were statistically significant. CONCLUSIONS: Academic achievement among children with asthma, at least those whose status is closely monitored in a structured treatment program, generally appears to be unaffected by asthma or by its treatment with appropriate doses of theophylline. PMID- 1513351 TI - Evaluation of a palpable breast mass. AB - A palpable mass in a woman's breast represents a potentially serious lesion and requires evaluation by history taking, physical examination, and mammography. The initial objective is to distinguish simple cysts from solid lesions, which can be accomplished with needle aspiration (Fig. 2). A solid lesion requires a firm diagnosis, and this usually calls for removing the lesion for histologic examination. A positive result on cytologic examination after aspiration is sufficiently accurate to justify one-stage diagnosis and treatment, with confirmation by examination of a frozen section obtained during the procedure. A negative or suspicious finding on cytologic evaluation is inconclusive, and outpatient biopsy is indicated. Perfection in diagnosis will require the removal of every solid mass. This can be expected to result in the biopsy of many benign lesions, but removal of many of them is desirable on other grounds. Although in some instances the probability of cancer may be exceedingly small, it is never zero. If biopsy is not recommended, the probability of cancer should be estimated so that the patient can decide whether the level of risk is acceptable to her. PMID- 1513350 TI - Effect of the Gulf War on infant and child mortality in Iraq. AB - BACKGROUND: Increased malnutrition and morbidity among Iraqi children after the onset of the Persian Gulf war have been reported by several fact-finding missions. The magnitude of the effect of the war and the economic embargo on child mortality remains uncertain, however. METHODS: We conducted a survey of 271 clusters of 25 to 30 households each, chosen as a representative sample of the Iraqi population. The households were selected and the interviews conducted by an international team of public health professionals independent of Iraqi authorities. In each household all women 15 to 49 years of age were interviewed, and the dates of birth and death of all children born on or after January 1, 1985, were recorded. RESULTS: The study population included 16,076 children, 768 of whom died during the period surveyed (January 1, 1985, to August 31, 1991). The age-adjusted relative mortality for the period after the war began, as compared with the period before the war, was 3.2 (95 percent confidence interval, 2.8 to 3.7). No material change in the relative risk was observed after adjustment for region of residence, maternal education, and maternal age. The increase in mortality after the onset of the war was higher among children 1 to less than 12 months old (relative risk, 4.1; 95 percent confidence interval, 3.3 to 5.2) and among those 12 to less than 60 months old (relative risk, 3.8; 95 percent confidence interval, 2.6 to 5.4) than among those less than 1 month old (relative risk, 1.8; 95 percent confidence interval, 1.4 to 2.4). The association between the war and mortality was stronger in northern Iraq (relative risk, 5.3) and southern Iraq (relative risk, 3.4) than in the central areas (relative risk, 1.9) or in Baghdad (relative risk, 1.7). CONCLUSIONS: These results provide strong evidence that the Gulf war and trade sanctions caused a threefold increase in mortality among Iraqi children under five years of age. We estimate that more than 46,900 children died between January and August 1991. PMID- 1513352 TI - Case records of the Massachusetts General Hospital. Weekly clinicopathological exercises. Case 38-1992. A 72-year-old woman with orthostatic hypotension, syncope, and marked proteinuria. PMID- 1513353 TI - Preimplantation genetic diagnosis. PMID- 1513354 TI - Screening for unruptured intracranial aneurysms in autosomal dominant polycystic kidney disease. PMID- 1513355 TI - Life-threatening ventricular arrhythmias in patients with silent myocardial ischemia due to coronary-artery spasm. PMID- 1513356 TI - Family history, body-fat distribution, and the risk of breast cancer. PMID- 1513357 TI - Acquired syphilis in adults. PMID- 1513358 TI - Electronic data retrieval. PMID- 1513359 TI - Electronic data retrieval. PMID- 1513360 TI - Electronic data retrieval. PMID- 1513361 TI - Advertising by HMOs. PMID- 1513362 TI - Advertising by HMOs. PMID- 1513364 TI - Fumonisins--a current perspective and view to the future. PMID- 1513363 TI - Medicare versus primary care. PMID- 1513365 TI - Mutagenic potentials of fumonisin contaminated corn following ammonia decontamination procedure. AB - Naturally contaminated corn implicated in an outbreak of equine leukoencephalomalacia (ELEM) in southeastern Arizona was analyzed for mutagenic potential using the Salmonella/microsome mutagenicity assay before and after treatment with the ammonia procedure. Crude acetonitrile: water (1 + 1) extracts of high-pressure/ambient temperature (HP/AT) ammonia decontaminated, HP/AT plus low pressure/high temperature (LP/HT), and non-ammoniated fumonisin contaminated corn were tested for mutagenic potentials. Relatively pure (approx. 90%) fumonisin B1 standard was also tested for comparison purposes. The results of this experiment indicate that there was no mutagenic potential for the fumonisin B1 standard at the concentrations tested (100 micrograms/plate). Also, neither the naturally-contaminated corn nor the ammonia decontaminated samples elicited a positive mutagenic response. Fumonisin B1 levels, as determined by HPLC methods, were reduced by an average of 79% via the ammonia decontamination process. It is encouraging to note that, while further work is necessary to increase the efficacy of the ammonia process to reduce fumonisin levels, the ammonia process did reduce fumonisin levels and no mutagenic potentials were apparent in the treated corn. PMID- 1513366 TI - A review and update of animal toxicoses associated with fumonisin-contaminated feeds and production of fumonisins by Fusarium isolates. AB - During the 1989 corn harvest season, numerous reports of equine leukoencephalomalacia (ELEM) outbreaks and a pulmonary edema (PPE) syndrome in swine from several regions of the United States were received by the National Veterinary Services Laboratories (NVSL), Ames, Iowa. Previous and concurrent research linked Fusarium moniliforme and fumonisin-contaminated feeds to both diseases. Chemical and mycological investigations revealed fumonisin B1 (FB1) concentrations of 20 to 360 ppm in suspect swine feeds and 8 to 117 ppm in suspect equine feeds. Nonproblem feeds contained concentrations below 8 ppm. Fusarium moniliforme and Fusarium proliferatum were isolated from both problem and nonproblem equine and swine feeds. When cultured on autoclaved corn, the F. moniliforme and F. proliferatum isolated produced respective FB1 and fumonisin B2 (FB2) that range from less than 5 to more than 2450 ppm and less than 5 to more than 1000 ppm, respectively. Isolates from both problem and nonproblem feeds produces high levels (greater than 500 ppm) in culture. Reported here is a review of chemical and mycological data resulting from the study of several cases of PPE and ELEM. PMID- 1513367 TI - Fumonisins: isolation, chemical characterization and biological effects. AB - The fumonisin B mycotoxins (FB1 and FB2) have been purified and characterized from corn cultures of Fusarium moniliforme strain MRC 826. Fumonisin B1 (FB1), the major fumonisin produced in culture, has been shown to be responsible for the major toxicological effects of the fungus in rats, horses and pigs. Recent investigations on the purification of compounds with chromatographic characteristics similar to FB1 have led to the identification of two new fumonisins, FB3 and FB4. Fumonisins A1 and A2, the N-acetyl derivatives of FB1 and FB2 respectively, were also purified and shown to be secondary metabolites of the fungus. Short-term carcinogenesis studies in a rat liver bioassay indicated that over a period of 15 to 20 days, at dietary levels of 0.05-0.1%, FB2 and FB3 closely mimic the toxicological and cancer initiating activity of FB1 and thus could contribute to the toxicological effects of the fungus in animals. In contrast, no biological activity could be detected for FA1 under identical experimental conditions. These studies and others have indicated that the fumonisin B mycotoxins, although lacking mutagenicity in the Salmonella test or genotoxicity in the DNA repair assays in primary hepatocytes, appear to induce resistant hepatocytes similar to many known hepatocarcinogens. PMID- 1513368 TI - Experimental reproduction of ELEM. A study to determine the minimum toxic dose in ponies. AB - An experiment to gain insight into the minimum toxic dose of fumonisins was conducted by feeding ponies rations with known fumonisin concentrations. Naturally contaminated corn screenings (CS) were blended with pellets, corn, and molasses to formulate individual daily diets. One group of 4 ponies was fed a ration with fumonisin B1 (FB1) varying from less than 1 ppm to 22 ppm. A second group of 5 ponies was fed a ration at varying rates containing 8 ppm FB1 for 180 days. A panel of clinical chemistry parameters was evaluated twice weekly for both groups. One pony in the first group died of equine leukoencephalomalacia (ELEM) after 225 days of which the final 55 days' diet contained 22 ppm FB1. Approximately 9 days prior to death, this animal experienced elevated liver chemistry values. All 5 ponies in the second group experienced mild, transient, clinical signs; were euthanized at 180 days; and had mild, histopathological brain lesions. PMID- 1513369 TI - Biosynthesis of labeled fumonisins in liquid cultures of Fusarium moniliforme. AB - Fumonisins were readily produced in cultures of Fusarium moniliforme using a defined liquid medium. Addition of 200 mg of d3-methyl L-methionine to 100-ml cultures of F. moniliforme gave increased overall yields and high levels of deuterium (2H) incorporation into fumonisin B1. Approximately 90% of the resulting fumonisin B1 contained 6 deuterium atoms, while 9% of the product contained 3 deuterium atoms. Deuterium was shown to be incorporated exclusively in the methyl groups of the fumonisin backbone. The addition of as little as 5 mg of labeled methionine stimulated fumonisin production, but only about 5% of the fumonisin produced contained 3 deuterium atoms. PMID- 1513370 TI - A new fumonisin from solid cultures of Fusarium moniliforme. AB - A new fumonisin has been isolated from Fusarium moniliforme isolate MRC826 grown on corn. It was shown by NMR and mass spectrometry to be an isomer of fumonisin B2 that has free hydroxyl groups at C-3 and C-10 instead of the normal C-3 and C 5. This new fumonisin was detected in cultures of most isolates of F. moniliforme that were examined and was usually present at concentrations similar to those of fumonisin B2. Two isolates of F. moniliforme that produce significantly higher levels of this new isomer were identified. PMID- 1513371 TI - Taxonomy and biology of Fusarium moniliforme. AB - Fusarium moniliforme is one of the most prevalent fungi associated with basic human and animal dietary samples such as corn. This fungus has been suspected of being involved in human and animal diseases since its original description. Fusarium moniliforme is in the section Liseola along with F. proliferatum, F. subglutinans, and F. anthophilum. Cultural mutation often occurs when F. moniliforme is grown on a medium rich in carbohydrates. Mutants may be either the mycelial or pionnotal type and often lose virulence and the ability to produce toxins. Toxins produced by F. moniliforme are fusaric acid, fusarins, gibberellins, moniliformin, and fumonisins. The fumonisins are produced most often when F. moniliforme grows on corn. Fusarium moniliforme causes ear rot and stalk rot of corn and infection of corn kernels by this fungus is widespread. Infection of developing corn kernels may occur through the silks, through holes and fissures in the pericarp or at points where the pericarp is torn by the emerging seedling, and as a result of systemic infection of the corn plant by F. moniliforme. These models of infection as well as infestation of the kernel surface are important factors when considering the production of fumonisins in corn. PMID- 1513372 TI - The implications of naturally occurring levels of fumonisins in corn for human and animal health. AB - Contamination of corn with the fungus Fusarium moniliforme and its secondary metabolites, the fumonisins, has been associated with several human and animal diseases. This paper summarizes present knowledge and presents new data on the levels of fumonisins present in foods and feeds associated with these diseases as well as in commercial corn and corn-based products. The doses of fumonisins to which humans and animals consuming these products would be exposed are compared with those doses known to produce LEM in horses and hepatocarcinogenesis in rats. It is concluded that the known naturally occurring levels of fumonisins present a potential threat to human and animal health and realistic tolerance levels need to be set. PMID- 1513373 TI - Fumonisin B1 production and vegetative compatibility of strains from Gibberella fujikuroi mating population 'A' (Fusarium moniliforme). AB - We examined 25 strains of Fusarium moniliforme from eight states known to be associated with equine leukoencephalomalacia, a disease caused by the mycotoxin fumonisin B1. We determined the mating population, mating type, and vegetative compatibility group to which each of these strains belonged. All 25 strains were in the 'A' mating population; 12 were A+ and 13 were A-. Seventeen of the 25 strains were female fertile; these strains also averaged higher levels of fumonisin B1 production than did the strains that were female sterile. Nitrate non-utilizing (nit) mutants were generated in all 25 strains and each strain was assigned to a unique vegetative compatibility group based on the inability of the derived nit mutants to form a prototrophic heterokaryon with complementary nit mutants derived from any of the other strains examined. From these data, we concluded that the production of fumonisin B1 is a general characteristic of strains from the 'A' mating population of Gibberella fujikuroi associated with equine leukoencephalomalacia, since all 25 of the isolates that we examined were genetically distinct individuals. PMID- 1513374 TI - AAL toxins, fumonisins (biology and chemistry) and host-specificity concepts. AB - The AAL toxins and the fumonisins (FB1 and FB2) are structurally related and produced respectively by Alternaria alternata f.sp. lycopersici and Fusarium moniliforme. AAL toxin is characterized as a host-specific toxin, toxic to tomato, whereas fumonisin B1 causes equine leukoencephalomalacia. FB1 and FB2 were biologically active in susceptible tomato tissue (Earlypak-7) and animal tissue culture (rat hepatoma H4TG and dog kidney MDCK). Conversely, AAL toxin was also active in the rat and dog tissue culture cells. Both fungi produce toxin/s in culture that causes death in rats; these toxins are other than AAL and fumonisin. The peracetylated derivatives of AAL and FB1 are biologically inactive in both the tomato bioassay and the animal tissue culture systems. Acetylation of the amine renders AAL inactive. The hydrolysis product of AAL (phentolamine) is toxic to the susceptible tomato line whereas the phentolamine of fumonisin is not. AAL and FB1 can be analyzed by Continuous Flow Fast Atom Bombardment (CFFAB) and Ionspray Mass Spectrometry (ISM), both sensitive to the picomole range. The N acetyl of the TFA hydrolysis product of AAL and FB1 is determined by comparing the fragment ions at m/z 86 and 140 for FB1 and 72 and 126 for AAL. PMID- 1513375 TI - In vitro toxicology of fumonisins and the mechanistic implications. AB - The effects of fumonisins B1(FB1), B2(FB2), and the backbone of fumonisin B1 remaining after hydrolysis of the tricarballylic groups with base (HFB1) on sphingolipid biosynthesis were studied in both primary rat hepatocytes and pig kidney epithelial cells (LLC-PK1). Fumonisins were potent inhibitors of sphingolipid biosynthesis in hepatocytes (IC50 of FB1 = 0.1 microM), but overt toxicity was not observed. In renal cells, fumonisins also inhibited sphingosine biosynthesis (IC50 for FB1 = 35 microM), and caused decreased cell proliferation as well. Higher doses (greater than or equal to 70 microM) killed renal cells after exposure for 3 days. The inhibition of de novo sphingolipid biosynthesis was specific, and appeared to be at the site of ceramide synthase, which catalyzes the formation of dihydroceramide or ceramide by the addition of the amide-linked fatty acid to sphinganine or sphingosine. These results may account for the ability of fumonisins to cause equine leucoencephalomalacia and to promote tumor formation. PMID- 1513376 TI - Fumonisin-induced pulmonary edema and hydrothorax in swine. AB - Pulmonary edema and hydrothorax were observed in mature swine that died approximately 5 days after consuming corn screenings. These postmortem observations were reproduced in younger pigs that died within 1 week when fed the corn screenings under experimental conditions. Additionally, pulmonary edema and hydrothorax were induced in a pig that died after receiving 4 daily intravenous injections of fumonisin B1, a toxic metabolite produced by Fusarium moniliforme. PMID- 1513378 TI - A drug story. PMID- 1513377 TI - Subchronic toxicological investigations of Fusarium moniliforme-contaminated corn, culture material, and ammoniated culture material. AB - The fungus Fusarium moniliforme is ubiquitous on corn throughout the world and is a likely co-contaminant on corn infested with aflatoxin-producing Aspergillus flavus. Ammoniation has been used to detoxify aflatoxin-contaminated commodities. To determine the effect of ammoniation on the toxic potential of Fusarium moniliforme, male Sprague-Dawley rats were fed either diets containing 10% sound corn, ammoniated corn, corn culture material of hepatotoxic F. moniliforme strain MRC 826 (CM), or ammoniated CM for four weeks. They were observed for signs of toxicity and hematological, serum chemical and histopathological evaluations were made. Groups of male Balb/c mice were fed diets fortifies with 10% sound corn or CM for four weeks and evaluated by serum chemical and histopathological means to determine the suitability of mice as a model species for investigation of F. moniliforme-induced hepatotoxicity. Ammoniation was ineffective for detoxification of the CM. Hepatotoxicity and renal toxicity of CM and ammoniated CM were qualitatively similar, although renal tubular lesions appeared more advanced in rats fed ammoniated CM. Adrenal cortical cellular vacuolation was also found in CM and ammoniated CM-fed rats, while focal seminiferous tubular degeneration and aspermia were found only in the testes of ammoniated CM-fed rats. Fumonisin B1 concentrations of the CM and ammoniated CM diets averaged 99 and 75 ppm, respectively. CM containing 99 ppm fumonisin B1 also produced hepatotoxicity in mice similar to that found in CM-fed rats. Thus, mice may be useful for investigations of F. moniliforme-induced hepatotoxicity. PMID- 1513379 TI - Patient hair loss. PMID- 1513380 TI - Half-empty or half-full?: two responses to "elegy". PMID- 1513381 TI - Half-empty or half-full?: two responses to "elegy". PMID- 1513382 TI - Stereotactic radiosurgery. A review of "gamma knife" and "linac knife" technology and the unit at the Wake Forest University Medical Center. PMID- 1513383 TI - A woman with too much facial hair. Evaluating the possibility of attenuated 21 hydroxylase deficiency in hirsutism. PMID- 1513384 TI - The content of one doctor's practice. Relevance of the biopsychosocial model. PMID- 1513385 TI - Human immunodeficiency virus infection at New Hanover Regional Medical Center. PMID- 1513386 TI - Detection of sexually transmitted disease at premarital examination in a community health clinic. PMID- 1513387 TI - Diagnosis and reporting of sexually transmitted disease in Durham County, North Carolina. PMID- 1513388 TI - Patient-centered care is not enough. PMID- 1513389 TI - An interview with Daniel Carr and Ada Jacox. Interview by Carmella A. Bocchino. AB - When clinicians are aware of inappropriate variations in practice and have access to science-based recommendations for care, they usually change their practice styles and prescribing behavior. The first in a series of guidelines supported by the Agency for Health Care Policy and Research, "Acute Pain Management," was released in early March and recommended an aggressive, proactive, and collaborative approach to managing pain in patients recovering from surgery, medical procedures, or trauma cases. Co-chairs of the pain management panel, Drs. Daniel Carr and Ada Jacox, share their views on guideline design, the expert panel, consensus building, and their expectations for use by the clinical practice and research communities. PMID- 1513391 TI - Quantifying ambulatory care activities by time and complexity. AB - As economic considerations increasingly drive decisions in health care, the staffing mix and nursing roles in ambulatory care are often questioned. A patient classification system that quantifies nursing activities by time and complexity can be used to assist with the difficult task of matching nursing resources with patient care needs. PMID- 1513390 TI - Of rabbits and turtles: a time of change for unions. AB - Radical changes must take place if either the work place or the union is to succeed in the 21st century. Newer models of collective relationship must emerge to ensure the effectiveness and value of both union and management. PMID- 1513392 TI - The economic value of nursing. AB - The economic value of nursing relates to the purchaser's perspective. A three level model of nursing services purchasers is presented. Selected economic/management concepts are examined in relation to nursing's economic value and these three purchaser perspectives. PMID- 1513393 TI - SEPPD and HPPD: more effective control of nursing care costs. AB - A study of acute care hospital inpatient units demonstrates that the level of correlation between salary expenses per patient day (SEPPD) and hours per patient day (HPPD) is not strong enough to support the continued use of HPPD as the only parameter for monitoring and controlling nursing salary expenses. Findings indicate that chief nursing executives (CNEs) must consider hours and dollars, if they are to achieve effective fiscal management and appropriate influence within the organization. PMID- 1513394 TI - Severity of illness and resource allocation in DNR patients in ICU. AB - This study examined the differences in severity of illness and resource allocation between patients with do-not-resuscitate (DNR) orders and non-DNR patients in intensive care units. Severely ill intensive care patients with DNR orders continued receiving aggressive medical care following cardiac or respiratory arrest. The continued use of advanced therapies for DNR patients raises important questions about the use of costly intensive care resources. PMID- 1513395 TI - The evolution of a nurse manager council. PMID- 1513396 TI - Comparison of technologies in medication administration. PMID- 1513397 TI - Unit facilitator program. PMID- 1513399 TI - What does a BSN buy? PMID- 1513398 TI - Who's minding the store? PMID- 1513400 TI - [Double orientation tuning of neurons of the primary visual cortex of the cat at various levels of alertness]. AB - Orientation tuning (OT) of 225 visual cortex neurons was studied in immobilized cats by their responses to flashing light bars. It was found that 43% of neurons had monomodal OT and preferred the horizontal and vertical orientations, while 57% of neurons had double OT, i.e. they had main preferred orientation (PO) and additional PO (aPO). The mean angle between PO and aPO was equal to 71.4 +/- 2.4 degrees. In half of the cases the second maximum of OT was equal to the first one (mean: 0.7 +/- 0.03 from PO). Orientation characteristics of PO and aPO were practically identical. Under light and middle levels of narcosis half of the neurons with double OT became monomodal and 12% of monomodal neurons receive bimodal OT. Monomodal neurons had more often simple RF and invariance of OT to narcosis. The neurons with double OT had simple and complex RF equally often and their OT changed in narcosis. It is supposed that the neurons with double OT can be an angle and line cross detectors. Monomodal neurons may be the stable bench mark system of orientation coordinates. Interaction of these neuronal systems permits conducting an effective analysis of image features in the primary visual cortex. PMID- 1513401 TI - [Effect of the quantal composition, membrane potential and cholinoreceptor density on the temporal flow of the end plate current in the rat under conditions of acetylcholinesterase inhibition]. AB - The factors determining the decay of multiquantal end plate currents (EPC) were studied in the diaphragm muscle of rat by the comparison of EPC and miniature EPC (MEPC) amplitude--temporal characteristics. The decay of EPC (quantal content 25 100) was 1.2 times slower than the decay of MEPC when AChE was active. The AChE inhibition by armine or neostigmine made this difference 10-100 times higher. In most synapses the decay of multiquantal EPC can be approximated by a sum of two or three exponents. It depended on the quantal content and 3-exponential EPC could be transformed in 2-exponential and later to monoexponential ones if increasing concentration of magnesium ions. A slow component of EPCs (but not of MEPC) decay was highly sensitive to concentration of magnesium ions and had 3 times higher dependence of the membrane potential value than that one of MEPC. The irreversible blocking of receptors by alpha-bungarotoxin (alpha-BuTX) accelerated the decay of MEPC but the decay of multiquantal EPC changed in two phases: it was prolonged at the beginning of alpha-BuTX action followed by its acceleration, but never the time of the decay of EPC had achieved the apparent open time of ACh-activated ionic channels. It is suggested that during the multiquantal EPC generation not only the synchronization of opening but the kinetic of ACh-activated channels is changed, probably by blocking of this channels by high concentrations of endogenous ACh. PMID- 1513402 TI - [Structural changes induced by diethyl ether in cultured neuroblastoma cells]. AB - It has been found that neuroblastoma cells retract their neurites under the influence of ether in dose 1 ml in 15 ml of the cultural medium. Application of ether for two hours increases the ratio of the number of cells to the number of neurites from 9.94 +/- 2.12 in the initial state to 19.66 +/- 1.93 (P less than 0.002). An essential alteration of the cell shape and a decrease of their volume are observed as well. The reaction is typical of cells at different stages of morphological differentiation. The data obtained can be helpful for investigation of pharmacological preparations which prevent destruction of neurons under narcosis. PMID- 1513403 TI - [Serotonin-induced changes in the responses of electrically stimulated neuronal membrane of the mollusk]. AB - Serotonin (5-HT) added to washing solution has been studied for its effect on plastic properties of electrically excitable membranes of the parietal ganglion and identified PPa2 neurons in the isolated nerve system of snails. It is shown that neurons habituated to intracellular stimulation are able to restore action potential generation in the presence of 5-HT. Contrary, neurons possessing endogenous rhythmic activity (PPa2) generate train activity on the background of appearance of the membrane potential slow waves under the influence of 5-HT. A comparative analysis of 5-HT and chemicals with the known effect on activity of Ca and Ca-dependent K-channels (quinine, CoCl2, CdCl2) has demonstrated diversity of mechanisms underlying the 5-HT-ergic regulation of plasticity of the neuronal electrically excitable membrane. This difference stems from the processes of activation and blockade of Ca-dependent channels. PMID- 1513404 TI - [Changes in muscle tissue in vertebrogenic myofascial syndromes]. AB - The carrying ability of a spinal disc disturbed under axis load is found to be due to the displacement of a vertebra lying above it. The constant stretching of the extensively innervated soft tissues of the spine brings about a steady irritation process within the limits of the segmental part of the spinal cord and dysfunction of short profound muscles of the back. PMID- 1513405 TI - [Evoked activity of spinal cord neurons in the early period after cutting the sciatic nerve]. AB - The character of evoked activity of motoneurons, interneurons and Renshaw cells of white rats in low lumbar segments of the spinal cord was studied 5 days after cutting of sciatic nerves. A trustworthy rise of the amplitude of the excited postsynaptic potential (EPSP) of motoneurons on the side of nerve cutting was found. No reliable change of the membrane potential and threshold of the action potential emergence in these motoneurones was observed. Character of evoked activity of the Renshaw cells and interneurons did not differ essentially from the same of animals with the intact nerve. Possible mechanisms taking part in rising of the EPSP amplitude after cutting of the nerve are discussed. PMID- 1513406 TI - [Characteristics of skin thermo-mechano-sensitive receptors in animals and man]. AB - Changes in impulse activity of afferent fibres of the spinal dorsal roots connected with thermal receptors of cat's skin have been studied during acute experiments. Thermal sensitivity of the man skin has been studied in psychophysical experiments. Three types of reactions of fibers from heat receptors of the animal skin and two types from cold ones are obtained. All of them are mechano-sensitive reactions. They differ from each other in the depth of changes in frequency of average impulse activity, dynamic sensitivity, latent period of the reaction as well as in thresholds of thermal and mechanic sensitivity. It is supposed that there exists certain analogy between thermoreceptors of animals and men. PMID- 1513407 TI - [Hysteretic properties of movements in the elbow joint of unanesthetized cats with various methods of activation of muscle-antagonists]. AB - Movements of the elbow joint were studied in unanesthetized cats. These movements were evoked by microstimulation of the motor cortex or by vibration of the forepaw and then compared with reaction from direct stimulation of muscles in the anesthetized animals. Interaction of the hysteretic effects in the antagonistic muscles of the joint was studied during stimulation of two points of the motor cortex which produced opposite-directed movements. Coactivation of the antagonists was shown to increase both the joint stiffness and the uncertainty of the equilibrium value of the joint angle. The uncertainty myotatic reflexes during intracortical microstimulation were more significantly depressed in the muscle receiving more intensive activation from the given point in the motor cortex. On the contrary, myotatic reflexes during vibration were well expressed in the both antagonistic muscles. At the same time the uncertainty effects during forepaw vibration were displayed similarly as it was in the cortically evoked movements. PMID- 1513408 TI - [Muscle stretching and unloading reflexes during cortically evoked movements in unanesthetized cats]. AB - Extension and flexion cortically-evoked movements (CEMs) were studied in the framework of the experimental approach developed in the previous paper [5]. Movements in the elbow joint of an unanesthetized cat were evoked by intracortical microstimulation (ICMS) applied to the motor cortex, then they were tested using a torque disturbance method. Similarity of flexion and extension CEMs allowed producing their combined quantitative analysis and comparing the obtained characteristics with those defined for the movements which were evoked by direct stimulation of the biceps and triceps muscles in an anesthetized animal. Resulting stiffness and uncertainty index (UI) served as the main characteristics of the movement in the presence of torque disturbances. Depending on the relationship between the directions of the preceding movement and the initial phase of the disturbed one, CEMs were divided into two types: coinciding (1) and opposing (2) CEMs. When the preceding movement was evoked by switching on of ICMS, both types of the disturbed movements could be considered as realizations of the phasic myotatic reflexes: unloading (1) and stretch (2). Disturbed movements of type 1 were characterized by the narrow range of mean values of UI: 0.43-0.91 (1.2 Hz wave of torque disturbance) and 0.24-0.73 (3.2 Hz). Transition to type 2 enlarged sharply the spread in the means, they could be both positive and negative, variances of UI in separate realizations significantly increased as well. It is supposed that intensity of central processes controlling the disturbed movements is mainly connected with changes in their direction but not with the movement per se. PMID- 1513409 TI - [Inhibition of neuronal responses in the cat motor cortex, associated with attainment of a conditioned reflex when waiting for a flash of light]. AB - Inhibition of neuronal spike reactions associated with reflex movements and induced by the light flare at different moments during the conditioned stimulation (1 s.) has been found in chronic experiments on cats. The light flare in the interval of maximum probability of the reflex realization has promoted a rise in the neuronal latency by 300-400 ms and a decrease of their duration almost twice. Other realizations of the inhibition effect were weaker. PMID- 1513410 TI - [Effect of stimulation of the thalamic reticular nucleus on spino-bulbo-spinal reflex activity]. AB - The effect of the thalamic reticular nucleus (RN) stimulation on the spino-bulbo spinal reflex was studied in chloralose-anesthetized cats. RN stimulation was found to exert an inhibitory influence on this reflex. The same stimulation has also exerted an inhibitory influence on the spinal units activated during the spino-bulbo-spinal reflexes. PMID- 1513411 TI - [Slow changes in the membrane potential of superior cervical ganglion neurons of the rabbit, evoked by painful stimulation of the skin]. PMID- 1513412 TI - [Mechanoreceptor system of the respiratory center and its role in the control of respiration]. AB - The paper is concerned with the study of localization, firing properties, methods of activation and projection into the neuronal structures of the medulla oblongata as well as the reflex action of two types of mechanoreceptors of the lungs: slow- and rapid-adapting stretch receptors. Data on the first relay neurons monosynaptically connected with slow-adapting pulmonary stretch receptor afferents are presented. PMID- 1513413 TI - Comparison of the effects of volatile anesthetics in varying concentrations on brain energy metabolism with brain ischemia in rats. AB - The effects of varying concentrations and types of volatile anesthetics on neurochemical sequelae of brain ischemia were evaluated in the rat. Rats were assigned to treatment defined by a 3 x 3 design (anesthetic type and dose) with 5 rats/cell. Each group received halothane, enflurane, or isoflurane 0.5, 1.0, or 2.0 MAC (minimal alveolar concentration). This was followed by preischemic plasma glucose sampling, 5 min hypotension (30 mmHg) and 5 min decapitation cerebral ischemia. Preischemia plasma glucose increased with increasing anesthetic concentration and was highest in the isoflurane groups, varying from a low (+/- SD) of 7.19 +/- 1.79 mumol/ml in the 0.5 MAC halothane group to a high of 12.68 +/- 3.65 mumol/ml in the 2.0 MAC isoflurane group. End-ischemic brain lactate correlated with preischemic plasma glucose (r = 0.5, alpha = 0.5). We conclude that increasing concentration of volatile anesthesia with iv phenylephrine blood pressure support produces higher levels of plasma glucose and brain lactate with cerebral ischemia. PMID- 1513414 TI - Effects of bicuculline on [3H]SR 95531 binding in discrete regions of rat brains. AB - Effects of bicuculline in vitro, and acute and chronic treatment of a subconvulsive dose of bicuculline on [3H]SR 95531 binding to discrete regions of rat brains were studied in Sprague-Dawley rats. Scatchard analysis of the binding isotherms exhibited two populations of binding sites for [3H]SR 95531 in frontal cortex, cerebellum, striatum and substantia nigra. The apparent KD for high affinity sites was significantly increased in the frontal cortex and cerebellum in the presence of bicuculline (1 microM) with no change in Bmax. In contrast, the apparent affinity for low-affinity sites was not altered in the presence of bicuculline in these regions, whereas the Bmax was significantly decreased in the cerebellum. Following acute (2 mg/kg, i.p.) or chronic (2 mg/kg, i.p. for 10 days) bicuculline treatment, [3H]SR 95531 binding was also investigated in various regions of brains. The acute bicuculline treatment did not affect the [3H]SR 95531 binding in any of the regions studied. In contrast, apparent affinity for [3H]SR 95531 was significantly decreased in low-affinity sites of all regions studied in rats treated chronically with bicuculline. The Bmax values of high and low-affinity sites were significantly increased in the cerebellum with no change in the frontal cortex, striatum and substantia nigra. The present study demonstrates that chronic bicuculline treatment decreases apparent affinity of [3H]SR 95531 binding whereas the treatment increases apparent affinity of [3H]muscimol binding (1) in various brain regions. The results indicate that significant increase in Bmax of [3H]SR 95531 and [3H]muscimol binding in the cerebellum may be due to true up-regulation of GABA binding sites, involving increased de novo synthesis of receptor protein.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1513415 TI - Post-ischemic regional changes in acetylcholine synthesis following transient forebrain ischemia in gerbils. AB - The synthesis rate of brain acetylcholine (ACh) was estimated 30 min and 5 days following transient forebrain ischemia performed by 10 min bilateral carotid occlusion in gerbils. ACh synthesis was evaluated from the conversion of radiolabeled choline (Ch) into ACh after an i.v. administration of [methyl-3H]Ch. Endogenous and labeled Ch and ACh were quantified by HPLC. The synthesis rate of Ach was significantly decreased following 30 min of recirculation. The reductions reached 55.4% in the hippocampus, 51.2% in the cerebral cortex and 44.4% in the striatum. Five days after ischemia, the values returned to normal in the cerebral cortex and in the striatum, while ACh synthesis remained selectively lowered ( 30.4%, p less than 0.01) in the hippocampus. These cholinergic alterations may account for both early and delayed post-ischemic behavioral and mnesic deficits. PMID- 1513417 TI - Is there a high molecular weight glutamic acid decarboxylase? AB - Gel-filtration chromatography from crude extracts of mouse brain indicates the presence of a high molecular weight (HMW) (more than 750 kd) and a low molecular weight (LMW) (87.5 Kd) glutamic acid decarboxylase (GAD) when they are concentrated prior chromatography either by precipitation with salts or ethanol. Kinetically both peaks of GAD-activity exhibit an almost identical Km for L glutamate. Only LMW-GAD appears if the concentration step is carried out by ultrafiltration or if the extract is chromatographied without the concentrating step. HMW-GAD disappears from the chromatographic profiles if ethanolic extracts of GAD are treated with Triton X-100 before the chromatographic procedure. The sodium sulfate precipitation of a previously separated LMW-GAD gives rise to the reappearance of a HMW-GAD peak. Apparently HMW-GAD does not exist as a different molecular entity; indeed it may be an artefactual aggregation of LMW-GAD. PMID- 1513416 TI - On the activity of gamma-aminobutyric acid and glutamate transporters in chick embryonic neurons and rat synaptosomes. AB - The uptake of radioactive gamma-aminobutyric acid (GABA) and D-aspartate and the effect of SKF 89976-A, a non-substrate inhibitor of the GABA transporter, on this uptake have been investigated. Neuronal cultures from eight-day-old chick embryos grown for three or six days in vitro, were used as a model. For comparison, we also used the P2-fraction from rat. Neuronal cultures grown for three and six days expressed high-affinity uptake systems for [3H]GABA and for D-[3H]aspartate with an increasing Vmax during this period. The lipophilic non-substrate GABA uptake inhibitor, SKF 89976-A, inhibited transporter mediated uptake of GABA both in cell cultures from chicken, and in P2-fractions from rat. The results also showed that SKF 89976-A was a poor inhibitor of the uptake of D-aspartate. We found no non-saturable uptake of D-aspartate. PMID- 1513418 TI - Isolation of a tripeptide (Ala-Gly-Ser) exhibiting weak acetylthiocholine hydrolyzing activity from a high-salt soluble form of monkey diaphragm acetylcholinesterase. AB - A high-salt soluble form of acetylcholinesterase (AChE) was purified from monkey (Macaca radiata) whole diaphragm by a two step affinity chromatographic procedure using m-aminophenyl trimethylammonium-chloride hydrochloride-Sepharose and procainamide-Sepharose columns. The purified enzyme showed three major protein bands at 80 kDa, 78 kDa and 60 kDa on SDS-gel electrophoresis. [3H]Diisopropyl fluorophosphate ([3H]DFP) labeled enzyme also gave three radioactive peaks corresponding to these three bands. The purified enzyme pretreated with dithiothreitol and subjected to limited trypsin digestion gave a peptide fragment of molecular weight approximately 300 Da showing weak acetylthiocholine hydrolyzing activity as identified by Sephadex G-25 gel filtration. Sequence analysis showed that the active peptide fragment was a tripeptide with the sequence Ala-Gly-Ser. When the purified AChE was labeled with [3H]DFP, digested with trypsin and subjected to Sephadex G-25 chromatography, a radioactive peak that would correspond to the tripeptide fragment was seen. The kinetics, inhibition characteristics and binding characteristics to lectins of the active peptide fragment was compared with the parent enzyme. A synthetic peptide of sequence Ala-Gly-Ser was also found to exhibit acetylthiocholine hydrolyzing activity. The kinetics and inhibition characteristics of the synthetic peptide was similar to those of the peptide derived from the purified enzyme, except that the synthetic peptide was more specific towards acetylthiocholine than butyrylthiocholine. The specific activity (units/mg) of the synthetic peptide was about 29480 times less than that of the purified AChE. PMID- 1513419 TI - Changes of phorbol ester binding sites in rat brain following intracerebroventricular administration of thyrotropin-releasing hormone (TRH): an in vitro macroautoradiographic investigation. AB - We examined the influence of the intracerebroventricular (icv) administration of thyrotropin-releasing hormone (TRH) on protein kinase C (PKC) activities in various rat forebrain regions in order to cast light on the mechanism of extra pituitary non-endocrine physiological actions of TRH in the central nervous system. An in vitro macroautoradiographic method, with [3H]phorbol 12, 13 dibutyrate (PDBu) as the radioactive ligand, was used to investigate quantitative alterations of PKC activities. The optical densities for PDBu binding sites in the striatum and hippocampal formation were significantly increased after the icv administration of TRH, while those in the frontal cortex and septum were unchanged. These findings suggest that TRH may exert some of its non-endocrine functions through striatal and hippocampal neurons which used PKC in their second messenger systems. PMID- 1513420 TI - Arginine specific endopeptidases modify the aggregation properties of a synthetic peptide derived from Alzheimer beta/A4 amyloid. AB - A synthetic peptide corresponding to the first 28 amino acids of the Alzheimer disease amyloid beta/A4 peptide (3.2 kDa) aggregated to a high molecular weight (15 kDa) on SDS/urea polyacrylamide gels. Proteinase K, V8 protease, trypsin, and endopeptidase Lys-C readily degraded the aggregate. By contrast, when digested by endopeptidase Arg-C, a new polypeptide aggregate of higher molecular weight (16 kDa) was observed on denaturing gels without degraded smaller products. The new aggregate was comprised of three peptides: an intact beta/A4(1-28) and partially degraded peptides beta/A4(1-5) plus beta/A4(6-28). The results were confirmed by treatment of beta/A4 with other arginine-specific proteases: the gamma subunit of nerve growth factor and clostripain. The results indicate that arginine-specific proteases, including a growth factor processing enzyme, can nick aggregated beta/A4(1-28) amyloid and alter the configuration to produce a more complex aggregated form. If similar highly specific proteolytic mechanisms occur in the Alzheimer disease brain, the processing may promote the formation of high molecular weight aggregates that contribute to the development of relatively insoluble senile plaque core protein. PMID- 1513421 TI - Differences in the functional responses of two cell lines each expressing Pi hydrolysis-coupled muscarinic receptors. AB - Fluorescent oxonol dyes were used to measure changes in the membrane potential of two different cell lines each expressing Pi-hydrolysis coupled muscarinic receptors. Both SK-N-SH human neuroblastoma cells and m1-transfected A9 L cells express muscarinic receptors which, when stimulated, elicit a large increase in intracellular calcium, and release of inositol phosphates. Despite the similarity in this second-messenger response, muscarinic stimulation resulted in a hyperpolarization in the transfected A9 L cells whereas a small depolarization was observed in the neuroblastoma cells. The carbachol-mediated hyperpolarization of the transfected A9 L cells could be mimicked by increasing intracellular calcium with the ionophore A23187, suggesting that it may be mediated by calcium activated potassium channels. Exposure of SK-N-SH cells to A23187, on the other hand, had no effect on the membrane potential. These studies demonstrate that the activation of a second messenger system does not solely dictate the electrophysiological response of a cell, but that other factors such as the expression of ion-channels is critical in the determination of that response. PMID- 1513422 TI - Autoradiographic study on [3H]flunitrazepam binding in rat cortex and hippocampus after chronic ethanol treatment. AB - Ethanol alters almost all membrane functions, but it behaves essentially like a benzodiazepine-type GABAergic agonist. The mechanism by which ethanol affects the GABA/benzodiazepine complex is not clear. We studied the possible changes in [3H]flunitrazepam binding induced by chronic ethanol treatment, using light microscopic autoradiography, to try to elucidate the controversy underlying this topic. This technique allows us to measure densities of benzodiazepine receptors in different anatomical brain areas--visual cortex and hippocampus--which seem to constitute the anatomical support for the behavioral and physiological responses affected by ethanol. Autoradiographic studies on the visual cortex and hippocampus from rats chronically treated with ethanol do not show statistically significant differences in the binding of [3H]flunitrazepam with respect to control animals. Furthermore, we did not find either rostro-caudal or medio lateral differences in benzodiazepine receptor densities in each layer of the visual cortex. PMID- 1513424 TI - Peritumoral brain edema in meningiomas--influence of vascular supply on its development. AB - In a series of 35 patients with intracranial meningiomas, factors influencing the development of peritumoral brain edema (PTBE) were analyzed. We used numbers of the Edema Index as the extent of PTBE, which was obtained from the size of the meningioma and associated PTBE on a T2-weighted image of magnetic resonance imaging. We evaluated a relationship between the Edema Index and some factors that may play a role in the development of PTBE. Tumors in the frontal region and at the sphenoid ridge tended to be associated with larger PTBE than those in other locations (P less than 0.05). Histologically, meningotheliomatous and transitional meningiomas tended to be associated with larger PTBE than fibroblastic meningiomas (P less than 0.05). The meningiomas that had a vascular supply from the intrinsic cerebral arteries on angiography significantly correlated with severe PTBE compared with those supplied only from the meningeal side (P less than 0.01). We concluded that location, histology, and vascular supply from intrinsic cerebral arteries were the factors influencing PTBE. It is stressed that the vascular supply from the intrinsic cerebral arteries may have an influence on the extensive PTBE of meningioma. PMID- 1513423 TI - Ganglioglioma: 13 years of experience. AB - A 13-year retrospective review of 17 patients with gangliogliomas treated at the University of Iowa was conducted to investigate the association between tumor location, extent of resection, pathological findings, and patient prognosis. Thirteen were in the cerebral hemispheres and 4 in the midline. The mean ages at diagnosis and symptom onset were 16 and 8.8 years, respectively. The most common presenting symptom was seizures (11 patients); focal neurological deficit was seen in 5 patients and headache in 1. Patients with hemispheric tumors had an older age at time of diagnosis and a longer duration of symptoms. Pathologically, they had more microcalcifications, lymphocytic infiltration, microcystic degeneration, and eosinophilic bodies. Cerebral hemispheric tumors were more amenable to total resection than midline neoplasms, 77% versus 25%, respectively. In the patients with hemispheric tumors, 10 patients were tumor-free after total resection. Two of the 3 patients with partial resection had stable residual tumors. The third died of tumor progression. In the 4 patients with midline neoplasms, one was tumor-free after total resection. The other 3 had subtotal resection and radiation therapy. Two died within 2 years; the third is still alive with progressive tumor. Five of 9 patients who had seizure disorders and who underwent total tumor removal were seizure-free postoperatively. The other 4 patients and the 2 with partial surgical resection continued to have seizures. PMID- 1513425 TI - Proton magnetic resonance spectroscopy of pediatric brain tumors. AB - 1H magnetic resonance spectroscopy allows the regional quantitation of a number of metabolites from the brain in a noninvasive fashion. Spectra were obtained from 5 normal children and 25 children with brain tumors. Choline (Cho), N acetylaspartate (NAA), creatine and phosphocreatine, and lactate were quantitated in the form of ratios. The brains of normal children showed relatively high concentrations of Cho and NAA and virtually no lactate, as has been shown in adults. Benign astrocytomas and ependymomas were characterized by an elevation of the Cho:NAA ratio and an abnormal accumulation of lactate. Intrinsic malignant tumors were remarkable for an even higher Cho:NAA ratio but had no more lactate than was found in the benign tumors. Proton magnetic resonance spectroscopy may prove useful in characterizing neoplastic tissue in conjunction with more conventional imaging modalities. PMID- 1513426 TI - Decompression of the optic nerve sheath for vision-threatening papilledema caused by dural sinus occlusion. AB - Obstruction of the dural sinuses produces a clinical syndrome that resembles pseudotumor cerebri. In these patients, unremitting papilledema can cause blindness. We performed decompression of the optic nerve sheath in four patients who had occlusion of the dural sinuses. The operation achieved rapid relief of papilledema and recovery of vision. In three patients, fenestration of the nerve sheath of only one eye resulted in resolution of papilledema in both eyes. The procedure appears to relieve papilledema by filtering small quantities of cerebrospinal fluid into the orbit. It did not lower cerebrospinal fluid pressure in three patients who underwent lumbar puncture after surgery. Optic nerve sheath decompression is an effective operation for salvage of vision in patients with obstruction of the dural sinuses. PMID- 1513427 TI - The use of acetazolamide-enhanced regional cerebral blood flow measurement to predict risk to arteriovenous malformation patients. AB - Regional hemodynamic disturbances may complicate the treatment of certain cerebral arteriovenous malformations (AVM) and occasionally produce life threatening situations. Acetazolamide-enhanced quantitative regional cerebral blood flow studies were performed preoperatively in 35 patients to determine if patterns of vasoreactivity could be identified that might be markers for postoperative morbidity. Ipsilateral and contralateral regions of hypoperfusion were identified on resting studies, and a steal index was calculated by dividing the regional cerebral blood flow in the steal region by the flow in a normal cerebellar region. Flow in these regions of interest was again quantitated after the administration of acetazolamide, a known cerebral vasodilator. A delta value was calculated by subtracting the resting index values from the acetazolamide indices. Abnormally enhanced vasoreactivity (vasodilation) to acetazolamide stimulation was noted in these threatened territories in AVM that had perforating vessel feeding and angiographic steal phenomena, that developed hyperemic disturbances, and that resulted in poor outcomes. These findings call into question traditional theories of AVM-related hemodynamic decompensation and suggest unique smooth muscle derangements in cerebral vasculature in some AVM patients. PMID- 1513428 TI - Intramedullary cavernous angiomas of the spinal cord: clinical presentation, pathological features, and surgical management. AB - Cavernous angiomas of the spinal cord are rare lesions that can cause severe neurological symptoms. We add a series of 6 patients with intramedullary cavernous angiomas of the spinal cord to 30 patients with 31 histologically verified lesions already described in the literature. Four types of clinical presentation were seen in the 36 patients: 1) discrete episodes of neurological deterioration with varying degrees of recovery between episodes (13 patients); 2) slow progression of neurological decline (12 patients); 3) acute onset of symptoms with rapid decline (8 patients); and 4) acute onset of mild symptoms with subsequent gradual decline lasting weeks to months (3 patients). Of the 36 patients, 25 (69%) were women and 11 (31%) were men. The peak age of presentation was in the fourth decade. The thoracic spinal cord was affected in more than half the patients, with the cervical cord being the next most common location. Histological examination demonstrated the closely apposed vascular channels characteristic of cavernous angiomas. While most vascular channels were thickened and hyalinized, three angiomas had foci of small vessels resembling a capillary angioma. The available data suggest that surgical management of intramedullary angiomas should attempt complete extirpation. The lesions are often well circumscribed with a glial plane between the lesion and normal cord. However, spinal cord angiomas, unlike cranial lesions, have little room for enlargement before devastating symptoms occur. We achieved complete excision in all of our patients, who are all ambulatory and have improved symptoms. Little, if any, increase in neurological deficit was caused by myelotomy and lesion excision. These spinal lesions should be considered for surgery early, before repeated hemorrhage or enlargement can occur. PMID- 1513429 TI - Surgical treatment of syringomyelia based on magnetic resonance imaging criteria. AB - The treatment of syringomyelia includes many surgical options. We report a retrospective study of 65 patients with cavitary lesions of the spinal cord in whom the results of magnetic resonance imaging were used to develop specific treatment strategies. Intramedullary cavities were classified into three general types: 1) communicating syrinxes, which occurred with hydrocephalus and were anatomically continuous with the 4th ventricle (9 patients); 2) noncommunicating syrinxes, which were separated from the 4th ventricle by a syrinx-free segment of spinal cord (42 patients); and 3) atrophic syrinxes, which occurred with myelomalacia (14 patients). Noncommunicating syrinxes were further subdivided according to type: Chiari II malformations with hydrocephalus (5 patients), Chiari I malformations without hydrocephalus (11 patients), extramedullary compressive lesions (12 patients), spinal cord trauma (6 patients), intramedullary tumors and infections (6 patients), and multiple sclerosis (2 patients). Of the 65 patients, 39 underwent surgical treatment for progressive symptoms. Syrinxes occurring with hydrocephalus were treated empirically with a ventriculoperitoneal shunt. Excellent results were achieved in 7 of 7 patients with communicating syrinxes and in all 5 patients with Chiari II malformations. Two approaches were used in the treatment of syrinxes occurring with Chiari I malformations: Posterior fossa decompression improved symptoms but did not reduce syrinx size in 2 of 3 patients. In the third patient and in 3 patients who were not treated with decompression, shunting from the syrinx to the cerebellopontine angle cistern collapsed the cavity and resolved symptoms over the interval of follow-up (average follow-up, 1.5 years). Excision of extramedullary obstructions at the rostral end of noncommunicating syrinxes resulted in collapse or disappearance of the cavity in 6 of 7 patients. The remaining patient was treated effectively by a syringocisternal shunt. In all 4 patients with posttraumatic syringomyelia, good results were achieved by a spinal or syringocisternal shunt. Syrinxes associated with intramedullary masses were managed by biopsy or excision of the causal lesion and appropriate adjunctive therapy (6 patients). Patients with atrophic syrinxes were not operated upon except to relieve symptoms referrable to the causal lesion (4 patients). Recurrent syrinxes were not encountered in the 35 surviving patients over an average follow-up of 2.5 years. It is concluded that syringomyelia is a complex pathological disorder with several mechanisms of pathogenesis that requires a number of different treatment strategies. PMID- 1513430 TI - Estimating energy expenditure in traumatic brain injury: comparison of indirect calorimetry with predictive formulas. AB - A high degree of variability in energy expenditure has characterized the metabolic response to traumatic brain injury. A goal of parenteral or enteral repletion in this population is the precise estimation of caloric requirement to avoid complications associated with overfeeding and underfeeding. The first aim of this study was to evaluate three predictive formulas for comparison to measured energy expenditure (MEE) derived from indirect calorimetry in patients with traumatic brain injury. A total of 385 measurements were obtained in 102 patients and were compared concurrently with these predictive formulas. The best predictive method in this phase (bivariate regression) yielded r = 0.39 and P less than 0.001 (231 repeated measures). This best prediction, when compared with MEE, however, was able to capture values within 75 to 125% of MEE in only 56% of measurements. The two remaining formulas yielded r = 0.38 (P less than 0.001) and r = 0.23 (P less than 0.001) in 386 and 267 repeated measures, respectively. The second aim of this study was to evaluate the ability of additional nutritional markers to improve predictive ability. Regression analyses were performed on nutritional markers including indices of severity of injury, concurrent drug therapy, vital signs, neurological status, gluconeogenesis, protein synthesis/excretion, and immune response. The statistical results of the analysis on these multiple nutritional markers showed only heart rate, temperature, and number of days elapsed after injury to be significant predictors of MEE by indirect calorimetry in multiple regression analyses (R = 0.32; P less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1513431 TI - Predictors of survival and severity of disability after severe brain injury in children. AB - Seventy-five children, 16 years of age or younger, consecutively admitted to a level I trauma center over a 2-year period with severe nonpenetrating traumatic brain injuries were studied to assess factors predictive of survival and level of disability. The mortality rate was 33%; 31% had good recovery, 12% had moderate disability, 19% had severe disability, and 5% remained in a vegetative state. Factors were analyzed separately for potential effects on survival and, with fatalities excluded, for potential effects on the level of disability in survivors. Clinical status in the field and emergency room, although highly associated with survival, was less predictive of the level of disability in survivors. Glasgow Coma Scale scores 72 hours after injury, especially the motor component, were significantly better predictors of quality of survival. The severity of the brain injury and the presence and severity of extracranial injuries were strongly related both to survival and quality of survival. Chest injuries, in particular, were associated with increased mortality and morbidity, as was level of oxygenation; these factors were highly correlated. Factors most significantly predictive of survival were severity of total injuries as assessed with the Injury Severity Score and pupillary responses in the emergency room; factors most predictive of disability were Glasgow Coma Scale motor responses 72 hours after injury and level of oxygenation in the emergency room. These findings of differential predictive factors for outcomes of survival versus quality of survival have implications relevant both to clinical care and to research involving severely brain-injured children. PMID- 1513432 TI - Penetrating injuries restricted to the cauda equina: a retrospective review. AB - Thirty-three patients with penetrating injuries to the cauda equina were admitted to Ben Taub General Hospital (1980-1989). Thirty received gunshot injuries, and three had stab wounds. The average age was 30 years, and 30 patients were male. All patients had been admitted within 1 hour of injury and received spine films, myelography, or computed tomography. Deficits were "complete" if total loss of function existed and were "incomplete" if any function remained below the level of injury. Improvement at the end of followup was defined as any recovery of motor strength or regaining of a unilateral sensory level. Twenty-nine (88%) patients had incomplete neurological deficits. Of these, 15 (52%) had surgery, and of this patient group, 7 (47%) improved, 7 (47%) showed no change, and 1 (6%) worsened. Fourteen (48%) patients with incomplete deficits were treated conservatively; 10 (71%) improved, and 4 (29%) had no change. Four patients (12%) had complete deficits, 3 of whom had surgery, and all improved. One patient with a complete deficit was treated conservatively and did not improve. Ten (34%) patients had bowel or bladder dysfunction, and none improved regardless of the type of treatment. Complications (cerebrospinal fluid leak, pseudomeningocele, or wound infection) occurred in 5 (28%) operative patients and 1 (7%) conservatively treated patient. Early neurosurgical intervention for penetrating injuries of the cauda equina may be beneficial but carries an increased risk of complication. PMID- 1513433 TI - Radiobiology of radiosurgery: Part I. The normal rat brain model. AB - Because limited histological information is available from clinical radiosurgical experience, animal investigations are needed to answer questions regarding the biological response of both normal and pathological tissues. To determine the radiosurgical dose-response relationship of normal brain, we irradiated the right frontal lobe of 18 rats with a single 4-mm isocenter of stereotactic irradiation using the 201-source 60Co gamma unit. Maximal single-fraction doses varied from 30 to 200 Gy (2 rats per dose). All animals were observed for 90 days, killed, and histologically examined. No animal developed neurological dysfunction during that interval, regardless of dose. Animals that received 30, 40, 50, or 60 Gy had no pathological changes. In those given 70 Gy, we found occasional shrunken neurons, and at 80 Gy, rare arteriolar wall thickening. One animal that received 100 Gy had marked capillary endothelial cell degeneration and protein extravasation in the target volume, and the other had a 4-mm diameter necrotic region. Circumscribed cerebral necrosis also was identified in all 4 rats treated with either 150 or 200 Gy; astrocytosis, edema, and microhemorrhage were noted within the surrounding 1 to 2 mm of adjacent brain, and tissue outside that volume had a more normal appearance. We constructed a dose-response relationship based on the cellular, spatial, and temporal effects of focused single-fraction irradiation of the rat brain. To determine the temporal evolution of a known necrotic lesion (200 Gy), 12 other animals were killed (2 each) 1, 7, 14, 21, 30, or 60 days after radiosurgery.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1513434 TI - Influence of halothane, enflurane, and isoflurane on motor evoked potentials. AB - The influence of the inhalational anesthetics halothane, enflurane, and isoflurane on motor evoked potentials was studied in a total of 10 rabbits. Motor evoked potentials were recorded from the extremity muscles as well as from the epidural space of the spinal cord and cauda equina in response to electrical stimulation of the motor cortex at baseline conditions and equianesthetic concentrations (0.25 to 1.5 minimal alveolar concentration). Our results show a dose-dependent suppression of the electromyographic responses, which was similar with all anesthetics. Beyond 0.5 minimal alveolar concentration of any of the agents, electromyographic responses were absent. In contrast, spinal evoked responses representing neural activity were only slightly affected by the anesthetics. We hypothesize that the descending impulse elicited by the electrical stimulation of the motor cortex is mainly inhibited at the level of the spinal interneuronal or motoneuronal systems, because 1) electromyographic responses evoked by the stimulation of the cervical and lumbar nerve roots were only minimally affected by 1.5 minimal alveolar concentration halothane; and 2) spinal evoked responses were stable several minutes after cardiac arrest, indicating a subcortical action site of the electrical impulse. In conclusion, intraoperative monitoring of descending pathways by means of motor evoked potentials during anesthesia with the inhalational agents halothane, enflurane and isoflurane is only feasible when neural activity is evaluated. PMID- 1513435 TI - Subacute hydrocephalus after experimental subarachnoid hemorrhage: its prevention by intrathecal fibrinolysis with recombinant tissue plasminogen activator. AB - It is investigated whether intrathecal fibrinolysis may prevent subacute hydrocephalus after subarachnoid hemorrhage (SAH). In 19 cats, SAH was induced by the intracisternal infusion of 1 ml/kg body weight of fresh autologous blood at a rate of 0.6 ml/min. Eleven of those animals were treated by intrathecal fibrinolysis performed 24 hours after experimental SAH by intracisternal infusion of 3 mg of recombinant tissue plasminogen activator. Included were eight animals suffering from experimental SAH and four healthy animals retained for control. A computed tomographic scan performed 24 hours after the SAH displayed an acute hydrocephalus from the experimental procedure. Cerebrospinal fluid outflow resistance was 71 +/- 5.0 mm Hg/ml/min in the healthy animals, 265 +/- 19.8 mm Hg/ml/min in the nontreated animals 7 days after SAH, and 151 +/- 6.4 mm Hg/ml/min in the recombinant tissue plasminogen activator-treated animals 7 days after SAH (mean +/- standard deviation; changes significant with P less than 0.01). Postmortem planimetry of both lateral ventricles gives a mean of 3.7 +/- 2.7 mm2 in the healthy animals, 11.1 +/- 3.9 mm2 in the nontreated group after SAH (P less than 0.01), and 3.5 +/- 1.1 mm2 in the animals treated with recombinant tissue plasminogen activator. Intracranial pressure monitoring demonstrated marked intracranial pressure waves only in the nontreated animals after SAH. It is concluded that intrathecal fibrinolysis may prevent subacute hydrocephalus after experimental SAH. PMID- 1513436 TI - Archaeological origins of cranial surgery: trephination in Mexico. AB - Archaeological excavations in Mexico and South America have provided evidence that trephination of the skull was performed by the pre-Hispanic Mexican and Incan cultures. Because those who performed such operations on the skull, presumably for ritual, prophylactic, or therapeutic reasons, can be considered predecessors of modern intracranial surgeons, their techniques and results are a subject of considerable current interest. This article, adapted from a lecture presented to the 1986 Congress of Neurological Surgeons, summarizes published descriptions of 34 trephined South and Central American and Mexican skull specimens, 16 of which were unearthed in Mexico and are currently available for review in anthropological museums in Mexico. Examples of several surgical techniques used on these skulls are presented. Although some trephinations were performed by these early cranial surgeons for apparently therapeutic reasons on skulls with obvious evidence of traumatic fractures, the interpretation of the medical, psychiatric, cultural, or religious significance of such procedures remains largely speculative. PMID- 1513437 TI - Hair and neurosurgery. AB - The value of removing hair in preparation for neurosurgery is addressed in detail. One neurosurgeon's series, accrued over 40 consecutive months, of 638 prospectively examined, consecutive cases is the basis of this report. The overall surgical wound infection rate was 1.1%. The infection rate for the 313 cranial cases was 0.3% and 2.8% for the 218 procedures involving cerebrospinal fluid diversion (shunts). These data are discussed in the context of extensive nonneurosurgical and microbiological literature. It is concluded that the removal of hair by shaving does not lower the risk of surgical wound infection and may increase the risk. A technique for preparing skin and hair for neurosurgery and for the management of hair during neurosurgical procedures is discussed. PMID- 1513438 TI - A technique for stereotactic aspiration of deep intracerebral hematomas under computed tomographic control using a new device. AB - A new device, modified from the Nucleotome (Surgical Dynamics, Alameda, CA), was used for stereotactic aspiration of deep brain hematomas. Real-time monitoring by computed tomography allows a very safe procedure, and the risk of aspirating the surrounding brain is avoided. The technique was applied in 13 cases of deep brain hematomas. The intraoperative computed tomographic scan demonstrated that the mass effect was always immediately improved. Aspiration was stopped when the midline shift disappeared or was dramatically reduced. For most of the cases, a total aspiration of the hematoma was not needed (mean value of the aspiration rate of 71, 5%). No rebleeding and no complication related to the technique was observed. This technique was easily performed in emergency conditions. PMID- 1513439 TI - Radionecrosis secondary to interstitial brachytherapy: correlation of magnetic resonance imaging and histopathology. AB - Radiation-induced tissue damage in the central nervous system is a well-known complication of interstitial brachytherapy for brain tumors, yet imaging correlates have historically been based upon computed tomographic scans. We now present magnetic resonance imaging (MRI) to correlate radiation changes after interstitial brachytherapy with the histopathology. The central nervous system of a 38-year-old man with a left frontal cerebral glioma diagnosed by stereotactic biopsy was treated with interstitial brachytherapy (iridium-192, 47 Gy), followed by limited-field irradiation (45 Gy). With progressive deterioration, a second biopsy demonstrated radiation changes. Despite aggressive medical management, the patient died 9 months after completion of radiation therapy. Postmortem evaluation compared MRI scans of the intact, fixed brain with the histopathology. Axial sections (10 mm) obtained by MRI scan and autopsy brain slices were cut in the identical plane. Neuroimaging and histopathological findings of the lesion correlated within 2 to 3 mm resolution. In the peripheral white matter, MRI scan did not indicate the extent of radiation effect histologically. We suggest that MRI has limited utility in assessing the extent of impact of radiation on surrounding brain. PMID- 1513440 TI - Extraskeletal myxoid chondrosarcoma of the falx. AB - Intracranial cartilaginous tumors are unusual lesions, of which myxoid chondrosarcoma is the rarest. We describe this tumor arising from the falx in a 28-year-old woman treated at recurrence with a second operation and a radiation implant. The behavior of classic chondrosarcoma and mesenchymal chondrosarcoma is also reviewed. PMID- 1513441 TI - Surgical reversal of a subacute complete unilateral visual loss from an ovarian metastasis to the pituitary gland. AB - A 56-year-old woman with ovarian papillary cystadenocarcinoma that metastasized to the pituitary gland sought treatment with a 7-day history of total loss of vision in one eye. Ten days after transsphenoidal tumor resection, the patient's vision suddenly returned to baseline. This unusual case indicates that surgical decompression of the optic nerve and chiasm can completely salvage vision, even after prolonged total visual loss. PMID- 1513442 TI - Pleomorphic xanthoastrocytoma as a component of a cerebellar ganglioglioma: case report. AB - A 27-year old male patient underwent surgery for a cerebellar ganglioglioma in which a pleomorphic xanthoastrocytoma constituted the gliomatous element. Neither radiation nor chemotherapy was administered. The patient was well for 12 years and then he suffered a recurrence and underwent a gross total resection. Histological examination revealed a ganglioglioma with thrombosed blood vessels, areas of tumor necrosis, and scattered mitoses. These anaplastic changes, which were restricted to the glial component of the tumor, may herald a more aggressive clinical course. However, 11 months after the second operation, there have been no signs of tumor recurrence. PMID- 1513443 TI - "Subclinoid" carotid aneurysm with erosion of the anterior clinoid process and fatal intraoperative rupture. AB - We present the case of a patient with an aneurysm of the right internal carotid artery with subarachnoid hemorrhage. The aneurysm had resulted in erosion of the anterior clinoid process, but this was not recognized preoperatively. Intraoperative rupture during drilling of the clinoid necessitated vigorous packing that led to unintended carotid occlusion with subsequent fatal cerebral infarction. Preoperative recognition of the clinoid erosion may have prevented this catastrophe. To call attention to the potential for intraoperative rupture during exposure, we suggest the term subclinoid aneurysm to refer to aneurysms of the internal carotid artery that grow superolaterally and remain confined under the anterior clinoid process. PMID- 1513444 TI - Thrombosis of a giant aneurysm after extracranial-intracranial bypass. AB - A patient presenting with a giant, fusiform middle cerebral artery aneurysm underwent extracranial to intracranial bypass grafting before permanent occlusion of the aneurysm. The patient was to return 4 months later for endovascular treatment. Arteriography obtained before obliteration revealed complete aneurysmal thrombosis. No further treatment was deemed necessary. Factors predisposing to thrombosis are discussed. PMID- 1513445 TI - Pediatric brain stem infarction caused by a basilar and vertebral artery occlusion: case report. AB - Basilar and right vertebral artery occlusion, which caused a brain stem infarction, occurred in an 11-year-old boy. There have been nine previous cases of basilar artery occlusion with steno-occlusive lesion in the vertebral artery. It is suspected that dissection of the vertebral artery at the atlantoaxial level and a gradual progression of arterial dissection to the basilar artery were the major causes of this infarction. PMID- 1513446 TI - Language localization with activation positron emission tomography scanning. AB - We report the first instance of the use of 3-dimensional magnetic resonance imaging anatomically correlated to positron emission tomography (PET) scanning to identify language areas in a patient with an arteriovenous malformation (AVM) in the posterior speech region. The patient was a 24-year-old right-handed woman with an angiographically proven AVM (3-4 cm) in the left mid-posterior second temporal convolution in whom a left intracarotid injection of sodium Amytal produced significant language disruption. A baseline PET cerebral blood flow study identified the AVM, and an activation PET scan performed during the reading and speaking of simple words showed increased activity in the left parastriate cortex (the second visual area), in the left posterior third frontal convolution (Broca's area), and in the left inferior and midtemporal gyri (Wernicke's area). Increased activity was also noted in the right and left transverse temporal (Heschl's) gyri, in the left precentral gyrus, in the left medial superior frontal gyrus (the supplementary motor area), and in the right cerebellum. We conclude that activation PET scanning is useful in the preoperative assessment of patients who harbor cerebral AVMs in classically described speech regions. PMID- 1513447 TI - Carotid endarterectomy complicated by vein patch rupture. AB - Saphenous vein patch angioplasty has been used to improve the results of carotid endarterectomy by decreasing the incidence of postoperative occlusion and recurrent stenosis. A rare but potentially lethal complication of this technique is aseptic necrosis and rupture of the vein patch during the postoperative period. We report three cases of this phenomenon and review an additional 13 cases from the literature. This event generally occurs without warning 2 to 7 days postoperatively and may result in death or stroke. At reoperation, the central portion of the vein patch is necrotic, without evidence of infection. Technical considerations in the harvesting and preparation of these grafts are reviewed, as are the physical parameters predisposing certain vein patches to rupture. Saphenous vein harvested from the ankle has been linked to every reported case. Small diameter veins in particular appear to carry a higher risk of rupture. PMID- 1513448 TI - Informed consent: is it a myth? PMID- 1513449 TI - Closed continuous drainage of cerebrospinal fluid via lumbar subarachnoid catheter for treatment or prevention of cranial/spinal cerebrospinal fluid fistula. PMID- 1513450 TI - Central nervous system disease in patients with systemic lupus erythematosus. AB - Central nervous system (CNS) dysfunction in patients with systemic lupus erythematosus (SLE) is highly variable, although it is often described under a single heading of "neuropsychiatric" or "CNS" SLE. To clarify these CNS abnormalities, we studied 91 lupus patients, 63 of whom had CNS symptoms or signs, over 599 patient years. By placing patients in relatively homogeneous clinical groups (stroke, seizure, suicide attempt, hallucination, confusion, decreased alertness) we detected significant (but variable among groups) correlations with other manifestations of SLE, suggesting separate mechanisms for each CNS disorder. These correlations were lost if all "CNS-SLE" was considered as a single group. Patients with decreased alertness often had undetected systemic infections and had a high death rate from infection, rather than from CNS-SLE. The understanding of the pathogenesis and potential treatment of CNS disorders in lupus will depend on classifying the patients into homogeneous groups. PMID- 1513451 TI - Incidence of migraine headache: a population-based study in Olmsted County, Minnesota. AB - To determine the incidence of clinically detected migraine headache in the defined population of Olmsted County, MN, 1979-1981, we screened over 6,400 patient records from several diagnostic rubrics using the unique resources of the Rochester Epidemiology Project for population-based studies. We identified 629 Olmsted County residents who fulfilled the International Headache Society's 1988 criteria for newly diagnosed migraine headache between 1979 and 1981. The overall age-adjusted incidence was 137 per 100,000 person-years for males and 294 per 100,000 person-years for females. The highest incidence in females was among those aged 20 to 24 years (689 per 100,000 person-years), and in males, the highest incidence was among those aged 10 to 14 years (246 per 100,000 person years). From 1979 to 1981, there was a striking increase in the age-adjusted incidence in those under 45 years of age: the incidence increased 34% in women and 100% for men. This is the first population-based study of migraine incidence across all ages. PMID- 1513452 TI - Sensory and motor components of the restless legs syndrome. AB - The restless legs syndrome (RLS) is characterized by two major manifestations: dysesthesias in the legs and irresistible leg movements. We developed a procedure to quantify these manifestations, and we studied their temporal interrelationships. We found that many dysesthesias may either closely precede or follow occurrences of EMG-defined leg activity, or both manifestations may occur independently. These results suggest that the sensory and motor components of RLS may represent two distinct manifestations of a common basic neurologic defect. PMID- 1513453 TI - Attention and short-term memory in chronic fatigue syndrome patients: an event related potential analysis. AB - We recorded event-related brain potentials (ERPs) from 13 patients with chronic fatigue syndrome (CFS) and 13 matched normal controls. To assess attentional and memory deficits in CFS patients, we used a short-term memory task in which events occurred in different spatial locations and the patients made a rapid-response (RT) when a letter in a relevant location matched a letter in the prememorized set (Attention paradigm). Time-on-task effects on the ERP and behavioral measures were assessed over the 2 1/4-hour duration of this task. Both groups also performed a visual Oddball paradigm, with an RT, before and after the Attention paradigm. The patients' RTs were much more variable and, in nine of 13 cases, slower than the mean RT of the controls in both paradigms. The patients' memory performance was not significantly different from that of the controls and there were no group differences in the overall amplitude, latency, or scalp distribution of the N1, P2, N2, or P300 components of the ERP in either paradigm. The ERP and performance data from both paradigms suggest that perceptual, attentional, and short-term memory processes were unaffected in CFS patients and that the differences were limited to response-related processes. PMID- 1513454 TI - The Consortium to Establish a Registry for Alzheimer's Disease (CERAD). Part III. Reliability of a standardized MRI evaluation of Alzheimer's disease. AB - The Consortium to Establish a Registry for Alzheimer's Disease (CERAD) has developed procedures for standardized imaging and reporting of magnetic resonance (MR) findings in Alzheimer's disease (AD) for use by neuroradiologists in multiple medical centers using a variety of MR equipment and field strengths. After initial pretesting, we revised the protocol, expanded the summary rating scale to seven points, and added more illustrations. Fourteen participating neuroradiologists evaluated 28 MR scans of elderly patients, giving us the basis for judging interrater agreement. We obtained acceptable intraclass correlations (greater than 0.79) for rating the size of the lateral and third ventricles and the temporal horn. Less satisfactory intraclass correlations occurred when rating other areas, including (1) global atrophy of the brain (0.70); (2) dilatation of the sulci of the temporal lobe (0.66); (3) frequency, location, and severity of white matter lesions (0.77); (4) sylvian fissure enlargement (0.70); and (5) cerebral sulcal dilatation (0.64). We also saw considerable variation in the reporting of cortical and lacunar infarcts. Despite careful design of the rating methodology and readings by experienced neuroradiologists, we did not find satisfactory interrater agreement for interpreting MR findings in elderly subjects. These findings may explain the difficulties encountered in applying similar subjective rating techniques that meet with success at one institution to multicenter studies. More objective and reproducible procedures are needed for interpretation of neuroimaging findings of AD in multicenter studies. PMID- 1513455 TI - Predictors of cognitive and functional progression in patients with probable Alzheimer's disease. AB - We followed 65 patients with probable Alzheimer's disease, who were initially mildly to moderately impaired, with semiannual assessments of cognitive and functional performance for up to 4 years. Scores on the Mini Mental State Examination and a combination of instrumental and self-maintenance scale of activities of daily living were regressed on time of examination (measured in 6 month increments) to estimate cognitive and functional progression rates in individual patients. Lower scores on the verbal neuropsychological tests at the time of study entry, more aggressive behavior, and sleep disturbance during the first year of observation predicted faster cognitive progression. Faster functional progression was predicted by paranoid behavior, hallucinations and activity disturbances during the first year and the presence of extrapyramidal signs and lower scores on nonverbal neuropsychological tests at the time of entry into the study. Hallucinations occurred independently of cognitive severity and may identify a distinct subgroup of patients with rapid functional progression. Because of the greater significance of functional progression for caregivers' ability to manage patients, the presence of specific behavior problems early in the disease course may help to identify individuals who will experience greater functional decline and be at risk for earlier institutionalization. PMID- 1513456 TI - Occupation during life and memory performance in nondemented French elderly community residents. AB - Using data obtained during the baseline screening of the PAQUID cohort, an epidemiologic study on brain aging conducted in the Bordeaux area of France, we studied the relationship between lifetime occupation and memory performance in visual recognition (Benton Visual Retention Test; BVRT) and verbal induced recall (Wechsler Paired Associates Test; WPAT) in 2,720 elderly community residents. Occupational category was strongly correlated with poor memory performance for both the BVRT and the WPAT. Independent of the educational level, the risk of having poor memory performance was two to three times greater for farmers, domestic service employees, and blue-collar workers than for professionals/managerials. Occupational category should be taken into account in future cross-national studies on brain aging. PMID- 1513457 TI - Kynurenine pathway abnormalities in Parkinson's disease. AB - We measured metabolites of tyrosine and tryptophan (TRP) in the frontal cortex, putamen (PT), and pars compacta of the substantia nigra (SN) of control and Parkinson's disease (PD) brain tissues. Dopamine concentrations were significantly decreased in the PT and SN of PD tissue, regardless of L-dopa therapy. However, 3-O-methyldopa (3OMD) concentration showed a significant increase in each region of the PD group treated with L-dopa (PD[+]) as compared with both the control group and the PD group without L-dopa therapy (PD[-]). Therefore, 3OMD concentration appears to be a reliable marker of L-dopa therapy. Serotonin concentration was lower in each region of the PD groups than in the control group. Although the magnitude of decrease was greater in the PD(+) group, there was no statistical significance between the two PD groups. The same patterns of decrease were present in kynurenine (KYN) and kynurenic acid (KYA) concentrations, but the molar ratios of TRP to KYN and KYN to KYA were unchanged among three groups. In contrast, 3-hydroxykynurenine (3OHKY) concentration was increased in the PT PD(-) group and in three regions of the PD(+) group. Since the KYN pathway leads to formation of nicotinamide-adenine dinucleotide (NADH), the present results may be a further indication of a defect in NADH:ubiquinone oxidoreductase (complex I) in mitochondria in PD. PMID- 1513458 TI - Neurologic improvement in pure motor hemiparesis: implications for clinical trials. AB - Knowledge of the natural history of certain stroke subtypes is essential for the proper analysis and interpretation of clinical trials of stroke therapy. We evaluated the degree of weakness on admission and again 7 to 10 days later in 62 patients with pure motor hemiparesis (PMH) and 280 patients with motor deficits from other stroke syndromes (OSS). During the 7-to-10-day study interval, we found that the OSS group worsened slightly in motor function, whereas the PMH group improved (p = 0.01). Among those who improved in both groups, those in the PMH group improved to a greater extent than did those in the OSS group (p = 0.02). This occurred despite a greater frequency of worsening during the first 12 hours after stroke onset in the PMH group. By the fourth day following PMH onset, a majority of patients had improved, and this improvement was sustained until day 10. The two groups did not differ significantly in age, race, sex, history of cardiac disease, hematocrit, anticoagulation treatment, blood glucose, or medical complications in hospital. Lacunar infarcts occurred in 84% of PMH and 23% of OSS. Patients with PMH show significant spontaneous improvement in weakness within 7 to 10 days of admission, compared with patients with OSS. Stratification by admission stroke syndrome in clinical trials may be necessary before judging the efficacy, or lack thereof, of a therapeutic agent. PMID- 1513459 TI - Fast magnetic resonance diffusion-weighted imaging of acute human stroke. AB - Rapid MRI of the molecular diffusion of water demonstrated cerebral infarcts in 32 patients. We studied these patients at various times following the onset of ischemic symptoms and found that diffusion-weighted imaging revealed the infarcts sooner than conventional T2-weighted spin-echo imaging did; four hyperacute infarcts were shown only by diffusion-weighted imaging. Acute infarcts had lower apparent diffusion coefficients (ADCs) than noninfarcted regions did. This relative difference in ADC reached a nadir in the first 24 hours and rose progressively thereafter. Chronic infarcts showed a relative increase in diffusion and were readily distinguishable from acute infarcts. The technique takes less than 2 minutes to apply using a standard 1.5-tesla scanner in the clinical setting. Diffusion-weighted imaging has the potential to play a role in improving the early anatomic diagnosis of stroke and therefore in the development and implementation of early stroke interventions. PMID- 1513460 TI - Androgen receptor abnormality in X-linked spinal and bulbar muscular atrophy. AB - X-linked spinal and bulbar muscular atrophy (SBMA) is usually associated with feminization and hypogonadism. We were unable to find androgen receptor (AR) in the scrotal skin of three patients with SBMA, and propose that AR abnormality is the cause of the disease. PMID- 1513461 TI - Cardiovascular effects of human insular cortex stimulation. AB - Recent investigations indicate a site of cardiac representation within the left insular cortex of the rat. Moreover, the results of lesion studies suggest left sided insular dominance for sympathetic cardiovascular effects. It is unclear whether similar representation exists within the human insular cortex. Five epileptic patients underwent intraoperative insular stimulation prior to temporal lobectomy for seizure control. On stimulation of the left insular cortex, bradycardia and depressor responses were more frequently produced than tachycardia and pressor effects (p less than 0.005). The converse applied for the right insular cortex. We believe this to be the first demonstration of cardiovascular changes elicitable during insular stimulation in humans, and of lateralization of such responses for a cortical site. In humans, unlike the rat, there appears to be right-sided dominance for sympathetic effects. These findings may be of relevance in predicting the autonomic effects of stroke in humans and in the explanation of sudden unexpected epileptic death. PMID- 1513462 TI - Early viral brain invasion in iatrogenic human immunodeficiency virus infection. AB - We report a 68-year-old man who received an IV inoculation of WBCs for an indium radionuclide scan containing 600 to 700 tissue culture infectious doses of human immunodeficiency virus type 1 (HIV-1) from an HIV-1-infected individual. The recipient immediately received zidovudine, then was switched to dideoxyinosine and interferon-alpha, but died of hepatorenal syndrome and hepatic encephalopathy 15 days later. HIV-1 cultures were positive from the recipient's blood on day 14 but not days 0, 1, and 8. At autopsy, cultures of parietal lobe isolated HIV-1. HIV-1 nucleic acid was present in several brain areas, but not in several other organs, by two independent laboratories using the polymerase chain reaction. The brain showed mild perivascular cuffing and a mild lymphocytic meningitis, but there was no evidence of glial nodules, giant cells, or white matter abnormalities. HIV-1 pg41 viral antigen was seen by immunoperoxidase staining in rare infiltrating cells within perivascular and subpial spaces. Thus, HIV-1 was isolated from brain 15 days after mistaken HIV-1 inoculation and 1 day after virus was first recovered from blood. PMID- 1513463 TI - Periodic alternating gaze deviation in infancy. AB - Periodic alternating gaze is a rarely reported phenomenon. We have observed two cases that are unique in their early onset at birth and infancy. Multiple congenital defects of the posterior cranial fossa were present on MRI in both cases. A prominent abnormality shared by both was absence of normal structures in the region of the inferior cerebellar vermis. Periodic alternating gaze appears to be associated with pathologic changes in the hindbrain in these and other reported cases. PMID- 1513464 TI - Anatomic basis of amygdaloid and hippocampal volume measurement by magnetic resonance imaging. AB - Both the amygdala and the hippocampus are involved in the pathogenesis of a number of neurologic conditions, including temporal lobe epilepsy, postanoxic amnesia, and Alzheimer's disease. To enhance the investigation and management of patients with these disorders, we developed a protocol to measure the volumes of the amygdala and as much of the hippocampus as possible (approximately 90 to 95%) using high-resolution MRI. We present the anatomic basis of these two protocols and our results in normal control subjects. These volumetric studies of the amygdala may clarify the role of this structure in the pathogenesis of temporal lobe epilepsy. PMID- 1513465 TI - Immunologic study of vinculin in Duchenne muscular dystrophy. AB - Using immunologic techniques, we studied vinculin, a cytoskeletal protein associated with the membrane-skeleton of the muscle fiber. We examined muscle biopsies from five patients with Duchenne muscular dystrophy (DMD), two with Becker's muscular dystrophy (BMD), three normal human muscle samples, and four biopsies from disease control patients. All DMD patients showed patchy and low intensity immunostain at the sarcolemma of most fibers and, by immunoblot analysis, the content of vinculin was 42 to 61% of control values. There was no significant vinculin deficiency in samples from patients with BMD and other disease controls. The data suggest that vinculin content is reduced only in muscle where dystrophin is absent or sparse. PMID- 1513466 TI - Autosomal recessive form of hereditary motor and sensory neuropathy type I. AB - We studied pathologic changes in sural nerve biopsies from four patients with probable autosomal recessive (AR) hereditary motor and sensory neuropathy (HMSN) type I with a median motor nerve conduction velocity greater than 10 m/sec, comparing them with the pathologic features in autosomal dominant (AD) HMSN type I. The four recessive and two sporadic cases showed segmental demyelination. However, the classic onion bulbs of concentric Schwann cell processes, which occur in AD type I, were rare; many axons, also of a smaller size, were surrounded by onion bulbs of basal laminae. Schwann cells of the myelinated and unmyelinated types were involved in these onion bulb formations. Patients with HMSN type I who have many basal lamina onion bulbs should be considered as having AR inheritance. PMID- 1513467 TI - P3 recordings in patients with bilateral temporal lobe lesions. AB - We recorded event-related potentials to an acoustic "oddball" paradigm from 19 scalp derivations in five patients (three women and two men; age range, 44 to 56) who had global amnesia following encephalitis. CT and MRI showed severe bilateral lesions of anterior and midtemporal lobes. A P3 component, with a peak latency within the normal limits for age-matched controls, was recorded to "target" stimuli in four patients from all leads except Fp1, Fp2, F7, F8, T3, and T4. In the fifth patient, the P3 peak was delayed. PMID- 1513468 TI - Clinical, pathologic, and biochemical features of a cholesterol lipidosis accompanied by hyperlipidemia and xanthomas. AB - We describe the unique clinical and histopathologic features of a child with biochemical and immunocytochemical features of Niemann-Pick disease type C (NPC). Clinically, she was found to have multiple xanthomas of the upper aerodigestive tract with dysphagia and expressive language delay, splenomegaly, bony infarcts, and type IIb hyperlipidemia. Neurologic examination was otherwise normal. Microscopy revealed foam cells in her bone marrow, liver, tongue, tonsils, glottis, and in normal-appearing peritonsillar mucosa. Lipid analysis of a liver biopsy specimen showed a small increase in phospholipids, a twofold increase in sphingomyelin, a fivefold increase in cholesterol, and a marked (25-fold) increase in bis(monoacylglycerol) phosphate. Lysosomal acid hydrolase activities in cultured skin fibroblasts were nondiagnostic. Biochemical and immunocytochemical studies of cultured fibroblasts demonstrated lysosomal accumulation of unesterified LDL-derived cholesterol as well as delayed induction of homeostatic responses to endogenous cholesterol consistent with a diagnosis of NPC. Based upon these observations, we speculate that this patient could have a new phenotypic expression of NPC or represents a new cholesterol lipidosis biochemically resembling NPC. The chance occurrence of two separate lipid disorders seems less likely. PMID- 1513469 TI - Premature chain termination mutation causing Duchenne muscular dystrophy. AB - We identified a premature chain termination mutation in two brothers with Duchenne muscular dystrophy and correlated the mutation in one of the brothers with immunologic detection of dystrophin in skeletal muscle. Southern and polymerase chain reaction (PCR) studies of genomic DNA from the affected boys showed no major gene rearrangements. However, the noted absence of a HindIII Southern fragment containing the proximal portion of exon 48 led to the identification of a point mutation that creates a new HindIII restriction site in that exon. Exon 48 was amplified by PCR from DNA of the patients and other family members and digested with HindIII to show the mutation in the two boys and also in their mother and maternal grandmother. Direct DNA sequencing demonstrated a cytosine-to-thymine transition at nucleotide 7163 of dystrophin that converts a glutamine codon (CAA) to an ochre chain termination codon (UAA). This mutation predicts a truncated dystrophin missing the distal spectrin-like repeat region, the cysteine-rich domain, and the carboxy terminal. Immunohistochemistry of skeletal muscle from one of the affected boys revealed membrane-localized dystrophin in the majority of fibers detected by anti-dystrophin antibodies against (1) the amino terminal and (2) part of the spectrin-like repeat region; both regions would be present in the truncated dystrophin predicted by the chain termination mutation. This suggests that the carboxy terminal may not be an absolute requirement for dystrophin membrane localization. Very few muscle fibers also showed peripheral immunostaining using anti-dystrophin antibodies against the carboxy terminal, suggesting gene reversion, suppression, or read-through in these rare fibers. PMID- 1513470 TI - Detection of Duchenne and Becker muscular dystrophy carriers by quantitative multiplex polymerase chain reaction analysis. AB - We developed a method for the detection of Duchenne muscular dystrophy (DMD) and Becker muscular dystrophy (BMD) carriers. The method is based on the quantitative analysis of the products of standard multiplex polymerase chain reaction (PCR) from 18 different exons of the dystrophin gene, and is designated "QM-PCR." We detected deletions of one or more exons by standard multiplex PCR in DMD/BMD patients in 14 of 18 families examined (77.7%). The same deletions were readily demonstrated by QM-PCR in nine of 14 mothers (64.3%) and in another six of 22 possible carriers in these families. In five families where deletions were detectable in DMD/BMD patients, the mothers did not exhibit any deletions in their peripheral blood (35.7%). We obtained evidence for germinal mosaicism in at least two of these families and confirmed carrier identification by haplotype analysis using CA repeat polymorphisms at the 5' and 3' ends of the dystrophin gene. Furthermore, analysis of 17 coded DNA samples from normal females and obligatory carriers by QM-PCR showed that this technique could directly identify carriers of deletions in any of 18 different exons of the dystrophin gene. Its application in combination with existing techniques is expected to significantly improve the accuracy of carrier diagnosis in many families, and it may also be applicable to families in which pedigree and polymorphism information is insufficient for carrier diagnosis. PMID- 1513471 TI - Acute hydrocephalus in nonaneurysmal perimesencephalic hemorrhage: evidence of CSF block at the tentorial hiatus. AB - The acute hydrocephalus in patients with nonaneurysmal perimesencephalic hemorrhage suggests an extraventricular obstruction of CSF flow. We studied the occurrence of acute hydrocephalus and the site of cisternal blood in 40 consecutive patients with perimesencephalic hemorrhage. In all 11 patients with hydrocephalus, all perimesencephalic cisterns were filled with blood; this occurred in only five of the 29 patients (17%) without hydrocephalus (p less than 0.0001). We conclude that in the absence of intraventricular blood, filling of all perimesencephalic cisterns with blood is a necessary factor for the development of acute hydrocephalus. PMID- 1513472 TI - Metabolism of glucurolactone to glucarate in Parkinson's disease. AB - The metabolism of oral glucurolactone to serum D-glucarate by the hepatic cytochrome P450 enzyme system was no different in 20 untreated Parkinson's disease (PD) patients as compared with 20 age- and sex-matched controls. There was no evidence for a deficit in hepatic enzymes in PD. PMID- 1513473 TI - Phenotypic expression of the myotonic dystrophy gene in monozygotic twins. AB - Phenotypic expression of the myotonic dystrophy (DM) gene is highly variable even within the same family. To investigate the importance of genetic and nongenetic factors on phenotypic variability, we studied phenotypic expression in two DM twin sets with monozygosity confirmed by DNA polymorphism analysis. Our observations suggest that genetic factors are primarily responsible for modulating pleiotropic expression of the DM gene. PMID- 1513474 TI - Treatment of cerebral aspergillosis after liver transplantation. AB - We report the treatment of cerebral aspergillosis with amphotericin B, flucytosine, surgery, and liposomal amphotericin B (L-AmB) after a liver transplant. The patient died 2 months after cessation of antifungal therapy, as a consequence of multiple-system organ failure. The only relevant postmortem finding in the brain was a small, encapsulated abscess containing hyphae. This case indicates that L-AmB is an effective alternative drug for cerebral aspergillosis. PMID- 1513475 TI - Midbrain syndromes of Benedikt, Claude, and Nothnagel: setting the record straight. PMID- 1513476 TI - Proceedings of a consensus development conference on standardized measures in diabetic neuropathy. Clinical measures. PMID- 1513477 TI - Proceedings of a consensus development conference on standardized measures in diabetic neuropathy. Morphological and biochemical measures. PMID- 1513478 TI - Proceedings of a consensus development conference on standardized measures in diabetic neuropathy. Electrodiagnostic measures. PMID- 1513479 TI - Proceedings of a consensus development conference on standardized measures in diabetic neuropathy. Quantitative sensory testing. PMID- 1513480 TI - Proceedings of a consensus development conference on standardized measures in diabetic neuropathy. Autonomic nervous system testing. PMID- 1513481 TI - Proceedings of a consensus development conference on standardized measures in diabetic neuropathy. Summary and recommendations. PMID- 1513482 TI - Coccidioidomycosis meningitis presenting as anterior spinal artery syndrome. PMID- 1513483 TI - Cavernous sinus syndrome and systemic lupus erythematosus. PMID- 1513484 TI - Acute respiratory failure from dopamine agonist withdrawal. PMID- 1513485 TI - Iron, Parkinson's disease, and neuroleptic malignant syndrome. PMID- 1513486 TI - Cramp-fasciculation syndrome. PMID- 1513487 TI - On antiethinyl estradiol antibodies. PMID- 1513488 TI - Immunoglobulins and stroke. PMID- 1513489 TI - Lenin's foot. PMID- 1513490 TI - Psychogenic seizures. PMID- 1513491 TI - SPECT and dementia. PMID- 1513492 TI - Intracerebral hemorrhage. PMID- 1513493 TI - Wegener's granulomatosis. PMID- 1513494 TI - Stroke evaluation. PMID- 1513496 TI - PHNs as community organizers. PMID- 1513495 TI - NLN's first century. PMID- 1513497 TI - Nurse practitioners & reimbursement. AB - Nursing's Agenda for Health Care Reform (1991) embraces primary health care as the focus of a restructured health care system. As part of this reformed system, consumers would access the most cost-effective providers in community-based settings. Removal of financial and regulatory barriers that limit consumer access to providers, such as lack of direct reimbursement by Medicare for nurse practitioners, should be eliminated according to this plan. Senate bills S2103 and S2104 have been recently introduced to the U.S. Senate mandating reimbursement for services provided by nurse practitioners, clinical nurse specialists, nurse midwives, and physician assistants at 97% of physician payment. The aim of this global legislation is to eliminate the current piecemeal mechanisms for nurse practitioner reimbursement and remove financial disincentives. Case examples presented in this article illustrate how obstacles to reimbursement limit access to care for consumers. Quality of care, opportunities for autonomous practice, and control of nursing practice issues have been highlighted as well by the case format. It is intended that these cases would be useful to support changes in patterns of nurse practitioner reimbursement. PMID- 1513498 TI - Nursing at the grassroots. AB - A new model of what constitutes political activity--recognizing grassroots issue involvement as well as partisan politics as legitimate political activism--offers hope for the prospect of the nursing profession becoming a strong political force in the future. Increasing involvement by nurses in health and environmental issues will be the nurses' means to achieve political strength. After all, it is that unique ethic of compassion, common to all nurses, that distinguishes a great political leader. PMID- 1513499 TI - The healing web. A transformative model for nursing. Part II. AB - The author and contributors continue the article that began in the February issue of Nursing & Health Care on the Healing Web project, "a collaborative effort of creative spinning and weaving." The purpose of the creative web management is to facilitate the healing of wounds within nursing and between nursing and medicine. PMID- 1513500 TI - Nursing's Agenda for Health Care Reform. PMID- 1513501 TI - The concept of a nursing center may be new to many.... PMID- 1513502 TI - AIDS issues. PMID- 1513503 TI - The migrant farmworker: health care challenge. AB - Migrant farmworkers comprise a severely medically underserved population, both nationally and in New Jersey. This article defines the migrant population, reviews their specific health problems, and illustrates the urgent need for the medical community's attention and resources. PMID- 1513504 TI - Maximum voluntary cough ratios reflect antitussive activity of inhaled albuterol. PMID- 1513505 TI - Monocyte activation in acquired immunodeficiency syndrome. AB - The monocyte plays a key role in the pathophysiology of AIDS and ARC. This preliminary report adds insight into monocyte activation associated with HIV seroconversion, by comparing recalcification times in healthy controls and HIV positive patients. PMID- 1513506 TI - HIV infection in kidney transplant recipients. AB - Four HIV-infected patients received cadaver kidney transplants. A fifth kidney transplant patient acquired infection through a blood transfusion. The course and prognosis of these patients with HIV infection are described and a review of the literature is presented. PMID- 1513507 TI - CLIA-88 final rule: Part 1. AB - The final rules implementing the Clinical Laboratory Improvement Act (CLIA) of 1988 were published. Physicians will see their office laboratories fall under control of the federal government as of September 1, 1992. Physicians need to understand the regulations. PMID- 1513508 TI - A public health campaign for New York State. PMID- 1513509 TI - The United States public health service and merchant seamen. PMID- 1513510 TI - Cardiac Kaposi's sarcoma in a patient with acquired immunodeficiency syndrome. PMID- 1513511 TI - Alcoholism-induced bone necrosis. AB - A total of 164 patients with alcoholism-induced osteonecrosis were seen over a 22 year period, from 1962 to 1984. Twenty-three percent of patients were female and 30.5% were black. The average duration of alcohol abuse was 9.5 years, ranging from 8 to 20 years. The presence of femoral head necrosis was diagnosed in patients aged 21-67 years; 28% of patients were under 40 years of age and 76% were under 50 years. Bilateral hip necrosis was present in 44.5% of patients and, within three years of the diagnosis of FHN, the presence of multifocal necrosis became evident in 23 cases at sites away from the hip (shoulders and knees). Hyperlipidemia was found in 38.4% of cases, involving both cholesterol and triglycerides. Serum amylase was elevated in 33 patients; liver dysfunction was present in 50; hepatomegaly was found in 32; and biopsy-confirmed cirrhosis was present in 22 cases. Hyperuricemia was found in 22 patients, some of whom had received steroids. Disabling hip pain was the first manifestation of disability related to alcohol abuse in 158 patients, most of whom required total hip joint replacement. This study supports the hypothesis that alcoholism-induced bone necrosis is caused by fat embolism linked to co-existent hyperlipidemia. The treatment of hyperlipidemia by dietary means or lipotropic medication and the cessation of alcohol abuse is advised. Multi-center studies employing such treatment should provide evidence of its effect on the evolution of necrosis as well as the incidence of bilateral hip femoral head necrosis and multifocal lesions. PMID- 1513512 TI - Lead screening and follow-up in an urban pediatric clinic. AB - The purpose of this study was to examine screening and follow-up procedures used in testing for lead toxicity at an urban pediatric clinic. A retrospective chart review of all patients with elevated zinc protoporphyrin levels was undertaken. In the first four months of 1990, 66 of 438 patients screened (15.1%) had elevated zinc protoporphyrin levels. Sixty charts were located and reviewed to evaluate five key interventional strategies. Iron therapy was implemented in 31 (51.2%), and follow-up was scheduled in 21 (35.0%). Two exposure histories and two dietary histories were documented (3.3% each). Only 26 children (43.3%) had venous blood drawn for lead-level determination. Eleven patients (18.3%) had none of these five steps documented, and an additional 26 (43.3%) received only one. Fifteen children (25.0%) received two interventions, six (10.0%) received three, and two (3.3%) received four. No patients received all five steps. Better procedures are needed at this site to ensure the implementation and documentation of diagnostic and therapeutic interventions in children with elevated zinc protoporphyrin levels. Other screening programs may benefit from examination for similar methodologic problems. PMID- 1513513 TI - Health care for seamen in the Port of New York. Part I: Recognizing the special needs of seamen. PMID- 1513514 TI - Epidemic Kaposi's sarcoma presenting with pleuropericarditis. PMID- 1513515 TI - Chronic recurrent multifocal osteomyelitis in adult women. PMID- 1513516 TI - Bilateral adrenal hemorrhage in polycythemia vera. PMID- 1513517 TI - Large endometrioma with intrauterine pregnancy. PMID- 1513518 TI - Appendiceal abscess presenting as an infected urachal cyst. PMID- 1513519 TI - The importance of differentiating between anabolic steroids and glucocorticoids. PMID- 1513520 TI - Double-tracer SPECT in patients with AIDS encephalopathy: a comparison of 123I IMP with 99Tcm-HMPAO. AB - Single photon emission computed tomography (SPECT) using N-isopropyl-p (123I)iodoamphetamine (123I-IMP) and 99Tcm-hexamethylpropyleneamine oxime (99Tcm HMPAO) was performed in 25 patients with different clinical stages of AIDS encephalopathy. The average interval between the two examinations was 7 days. In 15 of the 25 cases (60%) 99Tcm-HMPAO scans were different from 123I-IMP scans. Uptake defects of different extent were observed in 8 of 25 cases (32%), of different extent and different location in 3 of 25 cases (12%) and of identical extent but of different location in 4 of 25 cases (16%). Differences in the uptake patterns of 123I-IMP and 99Tcm-HMPAO with regard to extent and/or location were more commonly shown in patients with early acquired immunodeficiency syndrome (AIDS) encephalopathy (P = 0.0372). In this group, 99Tcm-HMPAO showed uptake defects of greater extent more frequently than did 123I-IMP (P = 0.0156). Our data indicate different brain uptake mechanisms of 123I-IMP and 99Tcm-HMPAO in early and advanced AIDS encephalopathy. PMID- 1513521 TI - Leg muscle scintigraphy with 99Tcm-MIBI in the assessment of peripheral vascular (arterial) disease. AB - A technique for using 99Tcm-methoxyisobutylisonitrile (MIBI) to evaluate leg muscle perfusion in the assessment of peripheral vascular disease (PVD) is described and evaluated. The uptake of MIBI in muscle groups is quantified and normalized to whole body activity. Eleven patients with PVD undergoing angiography and nine controls were studied. There was a significant difference in MIBI uptake in the calf (P less than 0.000 01) and thigh (P less than 0.0001) between the two groups on exercise. The technique has a sensitivity of 91% and specificity of 94% for the diagnosis of PVD. The technique can also effectively evauate the severity of disease as shown by significant correlations between exercise calf flow and angiographic severity (P less than 0.05) and Doppler ankle/arm pressure measurements (P less than 0.0005). Single photon emission tomography (SPET) of the calves was also performed in five controls and five patients with PVD. Uptake was significantly reduced in all muscle areas in patients with PVD and, amongst those with PVD, uptake was lower in muscle groups by occluded arteries. The potential role of 99Tcm-MIBI in the assessment of PVD and its advantages over other methods of assessment are discussed. PMID- 1513522 TI - High-resolution cardiac SPET study using fanbeam collimators in infants. AB - High-resolution three-headed single photon emission computed tomography (SPET) equipped with fan-beam collimators was applied to myocardial perfusion imaging in infants aged from 1 to 11 months (n = 5). A tabletop designed specifically for infants was fixed on the SPET couch to reduce the radius of camera rotation to 13.2 cm. Significant improvement in resolution was achieved with the fan-beam collimators compared to parallel-hole high-resolution collimators. With the administration of approximately 37 MBq (26-44 MBq) 201Tl, 5 min acquisition time was possible for SPET imaging, which provided good image quality in all patients. Thus, a smaller administration dose is possible within a practical short acquisition time. High-resolution fan-beam SPET imaging can be a routine diagnostic method for heart disease in newborn babies and infants. PMID- 1513523 TI - Evaluation of ventricular diastolic function in normal children using equilibrium radionuclide angiography. AB - Twenty children, aged 10.3 +/- 4.5 (3.3 to 17.5) years, were studied by equilibrium radionuclide angiography to establish a normal range for diastolic parameters. Ejection fraction (EF), peak ejection rate (PER) and time to peak ejection rate (TPER), peak filling rate (PFR) and time to peak filling rate (TPFR) were obtained from ventricular time-activity curves and their first derivative curves, and PFR and TPFR were considered as the diastolic parameters. Normal ranges obtained were as follows: EF, 60 +/- 8%; PER, 3.73 +/- 0.70 EDV-1; TPER, 109 +/- 25 ms; PFR, 3.84 +/- 0.51 EDVs-1; TPFR, 136 +/- 21 ms. There were significant correlations between PER and EF (P less than 0.001), PFR and EF (P less than 0.05), while age and heart rate had no influence upon these variables. Such normal ranges will be useful for evaluation of systolic and diastolic function in children with heart disease. PMID- 1513524 TI - Cell-targeted 114Inm and drug (BCNU) combination therapy in a rat acute lymphoblastic leukaemia. AB - A proportion of syngeneic female rats inoculated intramuscularly with a lethal T cell lymphoblastic (Roser) leukaemia are cured by a single intraperitoneal injection of bischloroethylnitrosourea (BCNU) (Carmustine) (10 mg kg-1) given towards the end of the preleukaemic phase (day 7). Additional therapy on day 4, using intravenous leukaemia cells lethally labelled with the radionuclide 114Inm, enhanced the overall cure rate by 30%. The spleen is a major site of indium concentration from the targeting cells so that the continuous local radiation field appears to result in a substantial reduction of the body load of leukaemia cells in the enlarged spleen particularly, thus enhancing the curative potential of the drug. The results demonstrate in principle that in patients in remission a single dose of targeted radiotherapy in the spleen combined sequentially with an appropriate drug might provide considerable aid in eliminating a residual population of leukaemia cells. PMID- 1513525 TI - The Scintigraphic Detection of Infectious Disease Meeting and the 7th International Research Group in Immunoscintigraphy and Immunotherapy (IRISR) Meeting. Nijmegen, The Netherlands, March 19-21, 1992. Abstracts. PMID- 1513526 TI - Antenatal diagnosis of pulmonary sequestration: a review. AB - The prenatal diagnosis of pulmonary sequestration has been demonstrated in 17 published reports, including a new case report presented here. In 11 cases (65 per cent), the definitive diagnosis was not appreciated until after birth, although a fetal mass was recognized on ultrasonographic study in the antenatal period. Seventy-five per cent of cases were thoracic sequestrations, and 25 per cent were abdominal lesions. Fetal hydrops, found in 35 per cent of cases, was universally associated with stillbirth or neonatal death. Polyhydramnios, pleural effusions, mediastinal shifts, pulmonary hypoplasia, and preterm labor were not uncommon findings. The high incidence of related malformations, well described in the postnatal literature, was remarkably absent in this antepartum series. Although the perinatal outcome for abdominal lung sequestrations is reasonably good, the prognosis in cases of thoracic sequestration remains guarded. Aggressive respiratory support after birth will not salvage those infants with underlying severe pulmonary hypoplasia. Early in utero catheter drainage may provide the best treatment for the pleural effusions associated with thoracic sequestrations, although this therapy remains under investigation. PMID- 1513527 TI - Prematurity 1992. PMID- 1513528 TI - Risk factors for Candida vulvovaginitis. AB - Although Candida vulvovaginitis occurs commonly, the reasons for its occurrence and recurrence are often unclear. Several potential risk factors have been described, including the recent use of antibiotics and oral contraceptives, the presence of diabetes mellitus, dietary practices, gastrointestinal colonization by the organism, clothing and sanitary protection practices, sexual communicability of the organism, and specific immunological defects. However, the data supporting each of these factors are conflicting, and to date none are predictive of infection. In this review, the data evaluating these potential risk factors are described. From this information, implications for clinical practice are discussed. PMID- 1513529 TI - Lead poisoning. AB - Construction workers who weld, cut or blast structural steel coated with lead based paint are at significant risk of lead poisoning. Although technology to control these exposures may not have existed when the lead standard was promulgated, it is available today. Employers who do not take steps to protect their employees from lead exposure may be cited and fined severely for their failure. PMID- 1513530 TI - OSHA reform. PMID- 1513531 TI - Intraocular lens implantation in the glaucomatous eye with loss of capsular support. PMID- 1513532 TI - Intraocular pressure level in glaucomatous and nonglaucomatous eyes after complicated cataract surgery and implantation of an AC-IOL. AB - The effects of a semiflexible, one-piece, open-loop anterior-chamber intraocular lens (AC-IOL) implanted after intracapsular or extracapsular cataract extraction complicated by posterior-capsular or zonular rupture on intraocular pressure (IOP) level and the control of previous glaucoma were studied in 48 eyes with primary implantation and in 10 eyes with secondary implantation. Fifty-four percent of the eyes with primary implantation had exfoliation syndrome; anterior vitrectomy was performed in 60.4%. An immediate pressure rise (IOP greater than or equal to 30 mm Hg) was observed in 29.3% of the eyes. The long-term IOP level (median follow up, 21.5 months) was less than or equal to 20 mm Hg in 83.7% and between 21 and 29 mm Hg in the remaining 16.3%. In three of the nine glaucomatous eyes, the medication had to be increased; in the remaining six, the IOP could be controlled with the previous or reduced medication or with none at all. In three out of the 49 (6.1%) nonglaucomatous eyes, glaucoma medication was started during the follow up. All of these eyes had exfoliation syndrome and two of the fellow eyes had similar IOPs and were receiving similar medication. The results indicate that the semiflexible, open-loop AC-IOL has little effect on IOP and seems to be a safe alternative, even in glaucomatous eyes, if a posterior chamber lens cannot be used. PMID- 1513533 TI - Direct scleral fixation of posterior chamber intraocular lenses using a special needle-holder. AB - We report a modified technique of direct scleral fixation of a posterior chamber intraocular lens (PC-IOL) using a specially designed intraocular needle-holder. The procedure was carried out in three eyes with posttraumatic subluxated cataracts; one with aphakic bullous keratopathy and with an accidental posterior capsular rent, and one with a superior zonulodialysis. The needle-holder greatly facilitated the procedure, enabling us to place the PC-IOL precisely in the ciliary sulcus with no subsequent decentration. This method avoids iris fixation and provides more secure scleral fixation of the PC-IOL. PMID- 1513534 TI - Central visual field, visual acuity, and sudden visual loss after glaucoma surgery. AB - The relationship between Snellen visual acuity and central visual field loss as determined by the Humphrey 10-degree test was examined in 96 glaucomatous eyes of 79 patients. The severity of the field defect was determined by the number of affected quadrants, defined as a sensitivity loss of at least 10 decibels from normal at the most central point of 1.4-degree eccentricity. The decrease in median acuity was gradual, one-half line per quadrant for one and two affected quadrants, and an additional one and one-half line to two lines for three and four quadrants. Loss of acuity was disproportionate when both temporal quadrants were affected. The major source of error was difficulty with fixation. One type, a prolonged fixation shift, was not related to short-term fixation losses. There was a significant correlation between acuity and foveal threshold over a wide range of both variables. Sudden visual loss from additional optic nerve damage was studied retrospectively in 96 eyes with advanced glaucoma and a central field defect. A frequency of 3% for any loss of visual acuity and a frequency of 1% for a loss to 20/200 or worse were noted. There were no apparent predictive factors. PMID- 1513535 TI - The effect of trabeculectomy on corneal topography. AB - Trabeculectomy is increasingly being performed earlier in the treatment of primary open-angle glaucoma (POAG). Surgically-induced alterations in corneal curvature resulting from filtering surgery may have a significant impact on patients, especially younger ones, whose vision may already be compromised by visual-field loss. Using data obtained by computer-assisted topographic analysis performed preoperatively and at 12 weeks postoperatively, we longitudinally studied the corneal surface changes induced by primary trabeculectomy in eight eyes undergoing surgery for POAG or normal-tension glaucoma. Additional data collected included refraction, keratometry, axial length, intraocular pressure, and pachometry. Five of eight eyes developed 1.50 to 2.50 diopters of steepening in the 90-degree meridian. One patient developed flattening in the 180-degree meridian without vertical steepening. Two patients had little change in the central optical zone. Of the six eyes with induced with-the-rule astigmatism, keratometry was less sensitive than topographic analysis in detecting the changes induced by trabeculectomy. Our data indicate that changes in corneal curvature are induced by filtering surgery, but may be undetectable without topographic analysis. PMID- 1513536 TI - Chronic corneal perforations. AB - We report the etiological profile and management with simple patch, tarsorrhaphies, conjunctival flaps, tissue adhesive, or penetrating keratoplasty of 104 chronic corneal perforations in a North India population. Chronic corneal perforations were observed in infective keratitis, degenerative keratolysis, neurotrophic keratitis, chemical burns, dry eyes, collagen vascular diseases, and following cataract extraction. A two-stage tissue adhesive application and adhesive-assisted debridement of epithelial lining at the cornea surface of perforation were important factors in healing. Although penetrating keratoplasties brought comparable anatomical and functional success in these cases, in developing countries, where facilities for keratoplasty and availability of corneal donor is poor, detection and management of small perforations in diseased cornea with tissue adhesive is recommended. PMID- 1513538 TI - An epidemiologic and pathologic study of globes enucleated following trauma. AB - This retrospective study examined demographic, clinical, and histopathologic factors in 24 traumatically ruptured globes that were enucleated at Wills Eye Hospital during a 2-year period. The majority of these injuries occurred in a violent assault setting with a blunt mechanism, during the evening and early morning hours, and in the fall and winter months. Most patients were black males, and 67% were substance abusers. Clinically, the initial visual acuity in 96% of the eyes was light perception or worse. Five of the eyes were enucleated primarily. Gross examination of the globes revealed that 92% of the wounds involved the sclera, 83% of the eyes had hyphema, and 71% of the lacerations were longer than 10 mm. Histopathologic examination demonstrated that the majority of eyes had fragmented or missing lenses, disrupted ciliary bodies, and detached choroids. Ninety-six percent of the retinas were detached. There was one case of acute endophthalmitis. PMID- 1513537 TI - Concurrent benign teratoid medulloepithelioma and pineoblastoma. AB - Teratoid medulloepithelioma of the ciliary body is a rare tumor usually occurring in young children. Primary tumors of the pineal gland are also quite rare and have a similar age distribution. We report the case of a 2-year-old girl who had a leukocoria of the right eye. Cataract surgery was performed; however, the patient developed a total retinal detachment refractory to treatment. She eventually developed early changes of phthisis bulbi and underwent an evisceration. Histopathologic examination revealed a benign teratoid medulloepithelioma containing islands of hyaline cartilage and rhabdomyoblasts. During the course of her evaluation, a pineoblastoma was discovered and surgically excised. While the association of pineal tumors with retinoblastomas has been well established, no such association has been reported for medulloepitheliomas. To our knowledge, this is the first recorded case of a benign teratoid medulloepithelioma occurring concurrently with a pineoblastoma. PMID- 1513539 TI - Orbicular muscle akinesia: a comparison, using electromyography, of three techniques. AB - Ninety patients scheduled for elective cataract extraction under local anesthesia received an inferolateral intraconal injection of 4 mL of etidocaine mixed with hyaluronidase. They were divided into three groups of 30 patients each according to the method used to provide orbicular akinesia. Those in group I had a nasal, intraorbital injection; those in group II underwent electrostimulation to locate branches of the facial nerve in the eyelids; and those in group III had the anesthetic agent injected subcutaneously into the lids. Ten minutes after the regional blockade, orbicular muscle activity of the upper eyelid, as measured by electromyography, was found to be higher in group I than in the other two groups. The muscular activity of the lower lid at 10 minutes, or of either of the lids at 20 minutes, was similar in all three groups. The use of electrostimulation did not yield better orbicular akinesia than the infiltration technique alone. Nasal injection improved globe akinesia. PMID- 1513540 TI - The tarsal pillar technique for narrowing and maintenance of the interpalpebral fissure. AB - We describe a tarsorrhaphy technique whereby an ipsilateral upper-eyelid tarsal pillar is sutured to a corresponding lower-eyelid recipient site. This technique allows maintenance of a narrowed interpalpebral fissure indefinitely, yet is easy to reverse without incurring lid-margin damage. Additionally, the procedure can be adjusted postoperatively to either narrow or widen the initial surgical result. We report our combined surgical experience in 35 consecutive procedures using this technique to treat eyes with exposure-related keratopathy of varied etiology, including facial nerve palsies, combined facial nerve palsy and trigeminal neuropathy with an anesthetic cornea, Graves' disease, congenital craniofacial anomalies, and severe keratitis sicca syndrome. The procedure was successful in improving exposure keratopathy symptoms in all 35 cases. Complications, reflecting the authors' learning curve with this new procedure, included intermarginal pyogenic granulomas, stretching of the tarsal pillar, minor lower-eyelid-margin eversion, and tarsal pillar dehiscence. PMID- 1513541 TI - Intraobserver and interobserver reproducibility of the Nidek EAS-1000 Anterior Eye Segment Analysis System. AB - The NIDEK EAS-1000 is a camera and computer system designed to facilitate measurement and analysis of the anterior segment of the eye. To evaluate the interobserver reproducibility of the system, three examiners assessed the anterior chamber depth and peripheral angle measurement in 20 disease-free eyes. Intraobserver reproducibility was determined by each investigator's photographing and analyzing the same eye on three different occasions. Interobserver correlation for the anterior chamber depth (using the first three readings of the same eye made by each examiner) was 0.97, with an 95% CI of 0.94 to 0.98. Interobserver correlation for angle measurement (again using the first three readings of the same eye made by each examiner) was 0.89, with a 95% confidence interval (CI) of 0.81 to 0.95. Intraobserver correlations for anterior chamber depth were 0.98 for each of the three examiners (mean, 0.98), wiht a 95% CI of 0.91 to 0.99. Intraobserver correlations for anterior chamber depth were 0.98 for each of the three examiners (mean, 0.98), with a 95% CI of 0.91 to 0.99. The intraobserver CI for angle measurement was 0.97 (range, 0.95 to 0.99). The intraobserver and interobserver reproducibility of the NIDEK EAS-1000 system was excellent. PMID- 1513542 TI - Anterior segment ischemia. AB - I present, to my knowledge for the first time, a case of anterior segment ischemia following a trabeculectomy performed under anesthetic. PMID- 1513543 TI - Microphthalmos with cyst. PMID- 1513544 TI - Reducing hypotony after Molteno procedure. PMID- 1513545 TI - Inflammation after cataract surgery in children. PMID- 1513546 TI - Sub-Tenon's local anesthetic for strabismus surgery. PMID- 1513547 TI - Superficial punctate keratopathy and bacterial growth in patients with unilateral aphakia using extended-wear soft contact lenses. AB - We prospectively examined corneal conditions and bacterial growth in 77 individuals with unilateral aphakia who were using extended-wear soft contact lenses. The ratios of positive bacterial growth (70.6-79.4%) from 34 patients with superficial punctate keratopathy were significantly higher than those (41.9 46.5%) from the 43 subjects with normal corneas. Bacterial growth was found frequently in patients with superficial punctate keratopathy who were older than 80 years and in those using soft contact lenses for more than 22 days. Several kinds of bacteria grew from the specimens. Among the most common were Staphylococcus epidermidis and Corynebacterium species. Pseudomonas aeruginosa grew from patients with superficial punctate keratopathy who were using extended wear soft contact lenses. PMID- 1513548 TI - Damage to the crystalline lens in infants of diabetic mothers: a pathology so far neglected? AB - Congenital cataract occurs in 90-95% of diabetic rat fetuses. The pathogenetic mechanism is triggered by fetal hyperglycemia and presents the following steps: (1) a high glucose concentration in the lens; (2) reduction of glucose to sorbitol by aldose reductase; (3) accumulation of sorbitol into the fibers of the lens creating a hyperosmotic effect, leading to (4) an infusion of liquid into the fibers, which (5) become hydropic and degenerate (vacuolization). This series of manifestations might also occur in fetuses of pregnant diabetic mothers. Post birth glycemia diminishes rapidly, and this favorable condition which decreases vacuolization is perhaps the reason why such degeneration has not yet been observed. Since the fibers of the lens are permanent cells, damage in the fetal period might later bring about negative consequences. We hope that someone will study whether this ocular pathology occurs in human infants born to diabetic mothers. PMID- 1513549 TI - Practically corrected visual acuity after extracapsular cataract extraction with or without intraocular lens implantation. AB - We examined retrospectively a total of 171 patients (236 eyes) who had undergone extracapsular cataract extraction (ECCE) with or without intraocular lens implantation (IOL). The best and practically corrected visual acuities were determined 6 months after surgery. Practically corrected visual acuity of the ECCE group was significantly worse than that of ECCE plus IOL group of patients who had undergone unilateral cataract surgery. In patients who had undergone bilateral surgery, visual improvement was almost optimal in both groups. With regard to practically corrected visual acuity, ECCE plus IOL was the preferable procedure for elderly patients who had had unilateral cataract. PMID- 1513550 TI - Intraocular muscle function in pseudoexfoliation syndrome. AB - Pseudoexfoliation (PE) material has been studied pathologically. However, there are no reports about intraocular muscle function in pseudoexfoliation syndrome (PXS). We studied intraocular muscle function in 12 patients (70.3 +/- 10.1 years of age) with ipsilateral PE material by measuring the time course of pupillary diameter change and accommodogram. Initial intraocular pressure (16.3 +/- 4.2 mmHg) was significantly higher in eyes with PXS than in normal fellow eyes (13.1 +/- 3.5 mmHg). The pupillary diameter of an affected eye was smaller than that of a fellow eye after bilateral topical application of tropicamide. Continuous near point testing revealed no significant difference; accommodative contractile time, relaxation time, and/or accommodopattern showed different patterns from the fellow eye. The results suggest that intraocular muscle function is disturbed in PXS. PMID- 1513551 TI - Mortality and morbidity in patients with central retinal vein occlusion. AB - We investigated the risk of mortality and morbidity in 78 patients with central retinal vein occlusion (CRVO) followed for more than 2 years (mean follow-up 7.2 years). Thirteen subjects died at an average of 7.0 years after CRVO. Five subjects developed myocardial infarction at an average of 2.8 years after CRVO, and 1 developed a cerebrovascular accident 3 years after CRVO. Patients with CRVO do not carry a higher risk of mortality and morbidity than matched controls derived from national surveys. PMID- 1513552 TI - Perimetric testing of tritan deficiency. AB - Three members of a family with dominantly inherited juvenile optic atrophy tested with a computerized perimeter employing violet and blue-green test lights and low intensity white background, all showed larger reduction in the relative sensitivity to violet light in the more central parts of the visual field compared with the periphery within 30 degrees from the center. Two subjects had typical optic atrophy, centrocecal scotoma and lower than normal visual acuity. In 1 subject with good visual acuity of both eyes, no optic atrophy was observed but there was impairment in the luminosity function (tested with white test object on white background) of the peripheral visual field. PMID- 1513553 TI - Goniodysgenesis of the eye with arthrogryposis multiplex congenita. AB - We report an autopsy case of 4-day-old male infant with arthrogryposis multiplex congenita studied by histological methods in respect to the ocular tissues. The eye examined was normal in size, and the retina, optic nerve, choroid, sclera and extracocular muscle showed no remarkable histological changes. However, the cornea was thickened, and the iris, trabecular tissue and ciliary body showed maldevelopmental changes, which were all compatible with goniodysgenesis. The clinical data of this case did not demonstrate any signs of congenital glaucoma, but the present study indicates that an infant with arthrogryposis multiplex congenita has a potential for infantile glaucoma with goniodysgenesis. PMID- 1513554 TI - Spectral response curves of congenital dichromats. AB - In a previous paper I have derived spectral response curves for the foveal cones of the CIE normal observer. These are based on the 1931 mixture data, the Judd 1951 V (lambda) curve, and the absorbance data of the pigments in the human cones. In the present paper I have found that the spectral response curves of congenital dichromats may be assumed to be similar to those of the CIE normal observer. PMID- 1513555 TI - Corneal exhaustion syndrome with long-term wear of contact lenses. AB - After many years of successful contact lens wear, 3 long-term wearers of polymethyl methacrylate (PMMA) lenses (14, 15, and 18 years) and 1 long-term wearer of thick hydrogel lenses (11 years) suddenly developed intolerance to their lenses. Symptoms included ocular discomfort, reduced vision, and photophobia. All patients exhibited an excessive open-eye edema response with low to moderate Dk lenses. Posterior corneal changes included distortion of the endothelial mosaic and moderate to severe endothelial polymegethism. Patients were successfully refitted with lenses having higher oxygen transmissibility. It is proposed that long-term hypoxia and acidosis accompanying PMMA and thick hydrogel contact lens wear may be responsible for a syndrome characterized by endothelial dysfunction which results in inadequate regulation of corneal hydration and subsequent intolerance to contact lens wear. This condition has been termed Corneal Exhaustion Syndrome (CES). PMID- 1513556 TI - Vision and task performance with monovision and diffractive bifocal contact lenses. AB - We measured vision and task performance on 26 presbyopes, ages 46 to 65 years, fitted with diffractive bifocal contact lenses (BFCL) and monovision contact lenses (MVCL). Distance contact lenses combined with reading spectacles (DCL) served as the control condition. Twenty subjects completed the 6-week study. All subjects wore BFCL and MVCL daily for a period of 3 weeks each. Performance times for three near tasks were 6 to 8% longer with BFCL compared with DCL and 2 to 6% longer for MVCL compared with DCL. There were significant reductions in distance visual acuity with BFCL (0.4 to 1.5 Snellen lines) and MVCL (0.5 to 0.8 Snellen lines) compared to DCL. At the conclusion of the study, given a choice between BFCL and MVCL, 2 of the 20 subjects chose to continue wearing BFCL, whereas 18 of the 20 subjects chose MVCL. Our results show greater visual compromise and decreased task performance with BFCL and MVCL compared to DCL and greater patient preference for MVCL. PMID- 1513557 TI - Comparison between near retinoscopy and cycloplegic retinoscopy in the refraction of infants and children. AB - We investigated the validity of replacing cycloplegic retinoscopy with a noncycloplegic, "near" retinoscopy technique. We refracted a group of 31 infants (less than 2 years) and 43 children (greater than 2 years) with both techniques, grading our level of confidence in the result. Near retinoscopy gave on average a less hypermetropic result than cycloplegic retinoscopy by 0.39 D. The difference was significant in infants and for low levels of examiner confidence. However, a repeatability study showed that much of the variability in the infant group could be attributed to the poor repeatability of either retinoscopy technique. Agreement between the two techniques is improved by changing the suggested adjustment factor from 1.25 to 1.00 D for children and to 0.75 D for infants. PMID- 1513558 TI - Vision defects in albinism. AB - We have examined the possible presence of color vision anomalies in 9 individuals (17 eyes, 1 blind) with fundus findings suggesting ocular albinism using the Ishihara plates, the 28-hue Roth test, and the Davico anomaloscope. Results indicate that four of these individuals show no sign of the anomalies expected in an albino in either of the two eyes. Of the remaining cases, two are simple deuteranomals in both eyes, according to Pickford's classification criteria. The rest have protanomaly; however, in these the deviation toward red appears in both eyes in only one subject, whereas in the other two subjects it appears in only one eye, their binocular color vision being basically normal. Our study shows that a large proportion of these albinos have photophobia, pendular nystagmus, strabismus, noticeable refractive errors (astigmatism and high myopia), and poor visual acuity [usually less than 6/30 (20/100) with correction]. The measurement of contrast sensitivity function (CSF) indicates that the frequency of 12 cpd cannot be perceived, even in binocular vision. PMID- 1513559 TI - Estimation of dioptric power from measurements of meridional power and curvature, sagitta, lens thickness, and prismatic effect. AB - A method published elsewhere for estimating dioptric power from meridional measurements is generalized here to allow for measurements of sagitta, lens thickness, and prismatic effect as well. Measurements may be of only one type or of combinations of types. Any number of measurements may be used. Within the usual limitations of first-order optics the method always works and gives all solutions when solutions exist. When no solutions exist it gives approximate solutions called least-squares estimates. At least one least-squares estimate always exists. A wide class of ostensibly distinct problems reduces to a single standard routine that is easy to execute with matrix-handling software. If there is reason to believe that the dioptric power is of some particular form then constrained estimation may be applied to find that form. PMID- 1513560 TI - The "L" in Dk/L. AB - We measured the Dk (oxygen permeability) of one specific hydrogel contact lens material (phemfilcon A, nominally 38% water content and ionic) by use of the conventional single chamber polarographic technique at 35 degrees C. When corrected for the boundary and edge effect, Dk was found to be 13 x 10(-11) cm2 ml O2/s ml mm Hg. (These units will be used for this term throughout the remainder of this report.) We also used the polarographic cathode as a model cornea to measure the Dk/L (oxygen transmissibility) of 7 powered contact lenses (-5 to +15 D) made from the same material by the same manufacturer. We found values ranging from 5 to 15 x 10(-9) cm ml O2/s ml mm Hg. (These units will also be used for this term throughout this report.) From analysis of these data, we found that any reasonable model (of the several previously proposed) for L could be used to predict the polarographically measured oxygen transmissibility of the low minus (-5 to -1 D) powered contact lenses, but that plus powered lenses, at least on this measurement apparatus, give Dk/L values that are closer to predictions based on the observed Dk and central thickness rather than any version of average thickness. PMID- 1513561 TI - Vertical diplopia onset with first-time bifocal. AB - A 39-year-old white female presented with symptoms of constant diplopia onset with a first bifocal correction. The association of these conditions required a careful differential diagnosis and special management considerations. Testing indicated an esotropia with a longstanding nonconcomitant superior oblique paresis which became manifest when she began wearing bifocals. A regimen of horizontal vergence range training in combination with a relieving vertical prism in a near correction were prescribed. An amount of prism which allowed comfortable sensory-motor fusion through both the distance and near portion of a bifocal spectacle correction was eventually ascertained. Information regarding etiology, etiologic incidence, differential diagnosis, and management of superior oblique paresis is also presented. PMID- 1513562 TI - Effect of ibuprofen on contrast sensitivity. AB - Therapeutic doses of ibuprofen (2-4'-isobutylphenyl-propionic acid) have been shown to have many deleterious effects on the nervous system. However, visual disturbances have been reported in fewer than 1% of the patients taking recommended doses of ibuprofen. The most commonly reported visual disturbances include: amblyopia, scotomata, and changes in color vision. To our knowledge, no studies have examined the effects of ibuprofen therapy on the contrast sensitivity function of an affected individual. Contrast sensitivity, Snellen visual acuity, color vision (D-15 test), and Goldmann visual fields were measured on 1 affected subject during and after ibuprofen therapy (800 mg/day for 2 days). Snellen visual acuity, color vision, and Goldmann visual fields were unaffected by the treatment. However, the contrast sensitivity was significantly depressed at low spatial frequencies while the subject was taking ibuprofen. The results, in concert with previous reports concerning the visual effects of ibuprofen, suggest that this drug can result in transient multifocal lesions of the visual pathway. PMID- 1513563 TI - Opaque contact lenses for YAG laser iridotomy occlusion. AB - Although a laser-produced iridotomy effectively controls angle-closure glaucoma the iridotomy can cause annoying visual effects. One solution is to fit a toric contact lens with an opaque portion to cover the iridotomy. PMID- 1513564 TI - Statistics notebook: entry IV.A: Confidence interval. PMID- 1513565 TI - Buckle-less repair of giant retinal tears. PMID- 1513566 TI - Declining disc rim area. PMID- 1513567 TI - PC IOLs in aniridia. PMID- 1513568 TI - Preparing for the impact of health care reform. PMID- 1513569 TI - Contact lens failure in keratoconus management. AB - PURPOSE: Surgery is indicated for keratoconus when management with contact lenses fails. The authors sought to determine the relative contribution of various preoperative patient and ocular factors to the ultimate causes of contact lens failure. METHODS: The records of unoperated eyes of keratoconus patients whose contact lenses were managed intensively before undergoing penetrating keratoplasty (PK) at the authors' institution between 1981 and 1990 were selected for study. Univariate and multivariate analyses were performed to identify risk factors for early contact lens failure. RESULTS: The records of 99 keratoconic eyes of 75 patients with an average age of 34 years and average keratometry readings of 57.5 diopters at presentation were studied. Cases had been followed for an average of 27 months before PK. The primary reasons for PK were a best corrected visual acuity of under 20/40 (despite good contact lens fit) causing disability for the patient (43%), contact lens intolerance (32%), frequent lens displacement (13%), and significant peripheral thinning of the cornea (12%). The referral source of the patient, sex, a history of PK in the fellow eye, or of contact lens wear in either eye did not alter the relative contributions of these parameters to surgery. CONCLUSION: Poor best-corrected visual acuity at presentation, higher keratometry readings (greater than or equal to 55 D), age (greater than or equal to 40 years), and duration of disease (greater than 5 years) were significantly associated with failure due to poor functional acuity and peripheral thinning, frequently leading to surgery within the first 12 months after presentation. PMID- 1513570 TI - Corneal epithelial alterations induced by disposable contact lens wear. AB - PURPOSE: To study the effect of disposable extended-wear soft contact lenses on the corneal epithelium. METHODS: Thirteen healthy patients (1 male, 12 females; average age, 26.3 +/- 7.6 years) with or without histories of previous contact lens use were recruited for this study. Specular microscopic pictures of the corneal epithelium and endothelium were taken with the help of a specular contact lens, before and after 3 months of contact lens use. The pictures were analyzed by means of a computer-assisted morphometric analysis system. RESULTS: The mean cell area and coefficient of variation (CV) of the mean cell area of the corneal epithelium before contact lens use were 639.4 +/- 84.0 microns 2 and 29.1 +/- 13.2, respectively. After lens wear, the mean cell area increased to 819.7 +/- 99.2 microns 2 (P less than 0.01), whereas the CV decreased to 20.0 +/- 6.1 (P less than 0.05). The corresponding values for the endothelium were 300.8 +/- 22.5 microns 2 and 36.4 +/- 7.3 before contact lens use, and remained at 322.3 +/- 27.8 microns 2 and 32.8 +/- 3.7 after contact lens use, respectively (P greater than 0.05). CONCLUSIONS: Based on the 3-month results, disposable extended-wear soft contact lenses caused similar enlargement of the mean cell area of the superficial corneal epithelium, as has been reported previously. It would appear that disposable lenses may cause the same metabolic and physiologic changes in the corneal epithelium as do conventional extended-wear soft contact lenses. PMID- 1513571 TI - Enhanced killing of Acanthamoeba cysts in vitro using dimethylsulfoxide. AB - PURPOSE: Acanthamoeba keratitis is difficult to treat and requires prolonged therapy despite the well-documented in vitro effectiveness of a variety of drugs. The authors propose that this may be due to the cysts formed by the organism in response to hostile conditions. Consequently, the study concentrates on increasing penetration of drugs effective against the parasite into the cysts using dimethylsulfoxide (DMSO). METHODS: The organism is forced to encyst in vitro on solid media by nutrient deprivation. In the first set of experiments, serial dilutions of a standard treatment regimen are applied to the organisms, and these treated cysts are then subcultured onto nutrient-rich material and observed for growth. The experiments are then repeated with DMSO added to the serially diluted standards. In a second set of experiments, the effects of retreatment on a larger concentration of organisms is examined. RESULTS: When applied to a cyst-only population of Acanthamoeba, none of three standard drugs, propamidine isethionate 0.1%, neomycin 1%, or miconazole 1%, was cysticidal. When combined with DMSO 30%, propamidine isethionate was clearly cysticidal even in low dilution. This was confirmed by the retreatment experiments using a larger, standardized cyst population. CONCLUSION: The authors propose that DMSO is acting as a "carrier" for the propamidine isethionate and increases its penetration into the normally drug-resistant cyst form of the organism. Because DMSO has been used topically in the past and shown to be quite safe, this may be a viable new therapy for this difficult condition. PMID- 1513572 TI - In situ collagen gel mold as an aid in excimer laser superficial keratectomy. AB - PURPOSE: The aim of this study is to evaluate the potential use of bovine type I collagen as an adjuvant to excimer laser keratectomy. METHOD: A suspension of collagen with the capability to polymerize into a gel was applied to the anterior corneal surface of freshly enucleated porcine eyes, using 35.0 diopter (D), 45.5 D, or 52.0 D contact lenses as molds. Keratometry, photokeratoscopy, slit-lamp photography, scanning electron microscopy, and light microscopy were performed on the new surfaces. Furthermore, an irregular corneal surface was created and a suspension of collagen was applied to mask protruding irregularities, therefore creating a smooth surface that was subjected to excimer laser keratectomy. Ablation rates for both collagen and cornea were measured. RESULTS: Collagen suspension placed on a cornea and molded with contact lenses created a smooth surfaced gel that conformed to the shape of the contact lens and adhered to the anterior cornea; it was optically smooth and regular as shown by photokeratoscopy, keratometry, and scanning electron microscopy. The corneal curvature was altered in accordance with the base curvature of the contact lens used. Results of keratometry showed resolution of pre-existing astigmatism without induction of new astigmatism. The ablation rate of the gel was not measurably different than that of cornea; hence, when applied to an irregular corneal surface, a smooth surface was created after excimer laser ablation. CONCLUSION: This study supports the potential value of collagen gel as an adjuvant to excimer laser keratectomy for removal of corneal irregularities as well as for correction of myopia or hyperopia with or without astigmatism. PMID- 1513573 TI - Excimer laser photorefractive keratectomy. 18-month follow-up. AB - PURPOSE: This study, comprising 120 patients (follow-up, 12 to 22 months; mean, 18 months), was designed to evaluate the efficacy and safety of excimer laser photo-refractive keratectomy. METHODS: Ablation zone diameter (4 mm), ablation rate (0.22 microns/pulse), fluence (180 mJ/cm2), and frequency (10 Hz) were kept constant, and all patients used a standard topical corticosteroid regimen. RESULTS: Overcorrection was followed by regression to a stable refraction by 4 months. At 1 year, 95% and 70%, respectively, of patients undergoing - 2.00 diopters (D) and -3.00 D corrections and 40% and 20% of those undergoing -6.00 D and -7.00 D corrections were within +/- 1.00 D of intended refraction. Anterior stromal "haze," maximal at 6 months and diminishing thereafter, was detected in 110 patients (92%). However, best-corrected Snellen visual acuity was reduced in only 22 (18%). Good correlation existed between haze and regression (r = 0.68). Night "halos," due to the relatively small 4-mm diameter ablation zone, were reported by 94 patients (78%) in the early postoperative period, and, at 1 year, 12 (10%) declined treatment of the other eye because of persistence of this problem. CONCLUSION: Marked individual variation was found after photorefractive keratectomy. However, in low myopia, predictability is "fair," and the procedure is safe. The authors conclude that excimer laser photorefractive keratectomy holds considerable promise for refractive surgery in the future. PMID- 1513574 TI - Ultrasound biomicroscopy of anterior segment tumors. AB - BACKGROUND: Ultrasound biomicroscopy is a new method of imaging the anterior segment of the eye at microscopic resolution using high frequency ultrasound. METHODS: A prospective study was performed to evaluate the use of ultrasound biomicroscopy in imaging anterior segment tumors. Forty-five patients underwent clinical examination followed by slit-lamp photography, anterior segment B-scan ultrasonography, and ultrasound biomicroscopy according to an established protocol. RESULTS: All lesions were clearly imaged by ultrasound biomicroscopy, while only 17 were detectable by conventional B-scan ultrasound. Ultrasound biomicroscopy allowed precise measurement and visualization of subsurface features in small tumors. Differentiation between solid and cystic lesions was easily achieved. The margins of ciliary body tumors could be more accurately defined. Histopathologic correlation was possible in four cases managed surgically. Ultrasound biomicroscopy images compared favorably with low-power microscopy. No complications were encountered. CONCLUSION: Ultrasound biomicroscopy proved a valuable new noninvasive technique in the evaluation of anterior segment tumors. PMID- 1513576 TI - Extracapsular cataract extraction and posterior chamber intraocular lens implantation in uveitis patients. AB - PURPOSE: Intraocular lens implantation in uveitis patients has been a controversial issue. The purpose of this study is to evaluate the visual and surgical outcomes of extracapsular cataract extraction (ECCE) and posterior chamber intraocular lens (PC IOL) implantation in a diverse group of uveitis patients. PATIENTS AND METHODS: The results of 39 cases of ECCE and PC IOL implantation in 30 patients with uveitis were retrospectively analyzed. Five patients (six eyes) had pars plana vitrectomies combined with ECCE and PC IOL implantation. Patient age ranged from 26 to 71 years (average, 53.0 years). Specific uveitic syndromes were determined for 22 patients (73.3%). The postoperative follow-up period ranged from 6 to 43 months (average, 20.3 months). RESULTS: Visual acuity improved postoperatively in 38 eyes (97.4%), and this improvement ranged from 1 to 11 Snellen lines (average, 7.5 Snellen lines). Visual acuity improved postoperatively to 20/40 or better in 32 eyes (82%). Seven eyes had visual acuity worse than 20/40, which was attributed to posterior segment abnormalities after ECCE and PC IOL implantation. Uveitis recurred in 20 eyes (51.3%), and postoperative cystoid macular edema (CME) was observed in 18 eyes (46.2%). In all cases, the recurrent uveitis and CME improved or resolved with corticosteroid therapy. CONCLUSION: These results suggest selected uveitis patients can have improved vision without unacceptable risk for 1 to 3 years after ECCE and PC IOL implantation. PMID- 1513575 TI - Soemmering's ring support for posterior chamber intraocular lens implantation during penetrating keratoplasty. Changing trends in bullous keratopathy. AB - BACKGROUND: Changing trends in cataract extractions have resulted in a new category of bullous keratopathy: corneal decompensation after complicated extracapsular cataract extraction. These cases of bullous keratopathy are associated with rupture of the posterior capsule, vitreous loss, and significant intraocular inflammation at the time of the original complicated extracapsular cataract extraction. METHODS: The authors reviewed 14 consecutive cases of penetrating keratoplasty for bullous keratopathy in which posterior chamber intraocular lens implantation was supported by remnants of the posterior capsule and/or Soemmering's ring without suture fixation. All 14 patients had a history of complicated extracapsular cataract extraction with capsule rupture and vitreous loss. RESULTS: All 14 patients had clear, compact grafts without migration of the intraocular lens with a mean follow-up of 12.1 months. Vision improved in 93% of cases, and there was no significant worsening of glaucoma. CONCLUSIONS: Pseudophakic bullous keratopathy after traumatic extracapsular cataract extraction with an anterior chamber intraocular lens and aphakic bullous keratopathy after traumatic extracapsular cataract extraction are two relatively new clinical entities that present new intraocular lens management options. Bullous keratopathy after complicated extracapsular cataract extraction should be recognized as a distinct clinical entity. Intraocular lens implantation into the ciliary sulcus with Soemmering's ring and peripheral capsular support provide the advantages of a posterior chamber intraocular lens without the risk of iris or scleral sutures. The authors predict that bullous keratopathy associated with traumatic extracapsular cataract extraction will become one of the more common indications for penetrating keratoplasty. PMID- 1513577 TI - Fibrinous uveitis and intraocular lens implantation. Surface modification of polymethylmethacrylate during extracapsular cataract surgery. AB - BACKGROUND: The causes of fibrinous uveitis after cataract surgery are unclear, but surface modification of polymethylmethacrylate (PMMA) is known to influence post-operative inflammation. One hundred twenty-five patients were entered into a prospective investigation designed to assess the effect of intraoperative surface modification of PMMA, by coating with a 2% hydroxypropyl methylcellulose solution, on the incidence of fibrinous uveitis after extracapsular cataract surgery and lens implantation. METHODS: Of the 125 patients entered into this prospective study, 90 received pretreatment with a 1% indomethacin solution. RESULTS: Fibrinous uveitis developed in 18(33%) of 54 eyes with dry lens implantation and in 1 (3%) of 36 eyes with coated lens implantation (P less than 0.005). Thirty-five eyes were not pretreated with indomethacin, and fibrin formation occurred in 6 (30%) of 20 dry implanted eyes and in 0 of 15 eyes with coated lens implantation (S = 0.02). CONCLUSIONS: Intraoperative modification of the PMMA surface of an intraocular lens during implantation significantly reduces the severity of postoperative inflammation, as manifest by the incidence of fibrinous uveitis. PMID- 1513578 TI - Effect of heparin surface modification of polymethylmethacrylate intraocular lenses on signs of postoperative inflammation after extracapsular cataract extraction. One-year results of a double-masked multicenter study. AB - PURPOSE: A heparin surface modified posterior chamber intraocular lens (IOL) was compared with a conventional polymethylmethacrylate (PMMA) IOL regarding postoperative complications caused by inflammation. METHODS: Five hundred twenty four patients from 10 different centers were included in a parallel group, double masked, multicenter study. RESULTS: The cumulative number of patients with inflammatory cellular deposits on their IOLs during the first postoperative year differed significantly in favor of the heparin surface modified group, with 29.8% of the patients having cellular deposits compared with 48.8% of patients in the control group. Cellular deposits were observed most frequently at 3 months after surgery, and the difference between the groups was most pronounced and statistically significant at this time. The same results were seen at 1 year, but the difference was not significant. The number of cellular deposits per patient, however, was significantly lower in the heparin surface modified group at 1 year. Cumulatively, there were significantly more patients with posterior synechiae in the PMMA group than in the heparin surface modified group during the 1-year follow-up. Complications were few and comparable between the groups. CONCLUSION: The results of this study indicate that heparin surface modification reduces the inflammatory response to PMMA IOLs. PMID- 1513579 TI - Treatment of postcataract fibrinous membranes with tissue plasminogen activator. AB - PURPOSE: The purpose of this study is to investigate the efficacy and toxicity of tissue plasminogen activator (tPA) in treatment of postcataract fibrinous membranes. METHODS: The authors injected 25 micrograms of tPA into the anterior chamber of 52 pseudophakic eyes with moderate to severe fibrinous membranes that developed after cataract surgery. RESULTS: Intraocular tPA injection resulted in complete fibrinolysis in 47 of 52 eyes (90%) and partial fibrinolysis in 5 of 52 eyes (10%). In cases of complete fibrinolysis, resolution of the fibrinous membrane occurred within 30 minutes in 22 of 47 eyes (47%) and within 1 hour in 25 of 47 eyes (53%). No evidence of toxicity was observed as measured by slit lamp biomicroscopy, intraocular pressure, and corneal endothelial cell density, size, and morphology. Complications of tPA administration included periorbital pain (4 eyes), anterior chamber hemorrhage (4 eyes), and anterior chamber turbidity (3 eyes). CONCLUSION: The authors believe that intraocular tPA is effective and safe in the treatment of postcataract fibrinous membranes. PMID- 1513580 TI - Management of dislocated lens fragments during phacoemulsification. AB - BACKGROUND: Dislocation of nuclear lens fragments during phacoemulsification can lead to a high incidence of glaucoma, uveitis, and poor visual acuity. The correct approach to these patients is uncertain. The authors report on eight patients who underwent pars plana vitrectomy with removal of lens fragments. METHODS: Charts of eight consecutive patients who developed dislocation of nuclear lens fragments into the vitreous cavity during phacoemulsification were retrospectively reviewed. All patients underwent a standard three-port pars plana vitrectomy with removal of the dislocated nuclear fragments by pars plana fragmentation. After the vitrectomy, the retina was inspected with indirect ophthalmoscopy. Tears were treated with cryopexy. A fluid-air exchange and scleral buckle were performed when indicated. RESULTS: Retinal tears were located at the vitreous base in four of eight patients. After vitrectomy, visual acuity improved in all patients, with 7 of 8 patients achieving visual acuity of 20/40 or better. The type of pseudophakia did not influence the final visual acuity. There were no cases of glaucoma, uveitis, or macular edema with up to 22 months of follow-up. CONCLUSIONS: These results suggest that large nuclear fragments dislocated into the posterior segment during phacoemulsification can be removed safely with pars plana vitrectomy and lensectomy with an excellent visual prognosis. Attempts to remove lens fragments during the phacoemulsification through an anterior wound should be avoided because of excessive vitreous traction, leading to retinal break formation. PMID- 1513581 TI - Retained intravitreal lens fragments after cataract surgery. AB - PURPOSE: The purpose of this study is to review the possible benefits and complications of vitrectomy for retained lens fragments after cataract surgery. METHODS: The authors reviewed the charts of 65 patients referred over a 12-year period for retained lens fragments after cataract surgery. Of these, 56 underwent vitrectomy and 9 were followed. Of these 56 eyes, 29 (52%) had received an intraocular lens (IOL) at the time of cataract surgery. RESULTS: Resulting complications from retained lens material included glaucoma (52%), corneal edema (46%), uveitis (56%), and decreased vision (100%). These sequelae responded equally to vitrectomy in eyes with or without an IOL and irrespective of type of cataract surgery (phacoemulsification or extracapsular cataract extraction). The timing of surgery did not statistically influence the final vision or the incidence of glaucoma. CONCLUSION: Removal of retained lens fragments allows rapid visual restoration, enhances resolution of uveitis, and improves control of glaucoma. Insertion of an IOL at the time of cataract surgery in the face of dislocated lens fragments is not contraindicated provided that it could be performed safely. PMID- 1513582 TI - Aniseikonia and stereoacuity in pseudophakic patients. Unilateral and bilateral cases. AB - PURPOSE: To evaluate the efficacy of intraocular lens (IOL) implant procedures, analyzing visual function of the operated eyes and the resulting binocular vision. METHOD: The authors measured aniseikonia and stereoacuity in patients with both bilateral and unilateral posterior chamber intraocular lenses (PC IOLs). The aniseikonia was measured with the New Aniseikonia Test; the stereoacuity was evaluated with the Titmus Stereotest. RESULTS: In 41 patients with bilateral PC IOLs, aniseikonia measured with the New Aniseikonia Test ranged from 0% to 4% (mean, 0.76%; standard deviation = 1.04%). The average stereoacuity evaluated with the Titmus test was 7.68 circles (less than 60 seconds; range, greater than 800 to 40 seconds of arc), with 36 of 41 patients (87.8%) showing a stereoacuity less than or equal to 100 seconds of arc. In 37 patients with unilateral PC IOLs, the aniseikonia ranged from 0% to 6% (mean, 0.97%; standard deviation = 1.13%). Their stereoacuity also ranged from greater than 800 to 40 seconds (mean, 7.67 circles) (less than 60 seconds). In this group, 34 of 37 (91.8%) patients showed a stereoacuity less than or equal to 100 seconds of arc. CONCLUSION: Although the problem of aniseikonia still remains, a significant number of patients attain good binocular function after unilateral and bilateral PC IOL implantation. PMID- 1513583 TI - Corneal diameter, axial length, and intraocular pressure in premature infants. AB - PURPOSE: Seventy premature infants 25 to 37 weeks' postconceptional age were examined during their first week of life to determine the correlation of corneal diameter, axial length, and intraocular pressure with gestational age and birth weight. METHODS: Corneal diameter measurement was determined with corneal templates, total axial length with standardized A-scan ultrasound, and intraocular pressure with a Tonopen II tonometer. RESULTS: Corneal diameter and total axial length showed parallel linear increases from 6.2 mm to 9.0 mm and 12.6 mm to 16.2 mm, respectively; however, no significant correlation was found between intraocular pressure and gestational age or birth weight. The mean intraocular pressure was 10.3 mmHg (standard deviation, 3.5). CONCLUSION: Normative values are established for corneal diameter and total axial length as they relate to birth weight and gestational age, and a mean and standard deviation for intraocular pressure in the premature newborn. These values will aid the ophthalmologist in assessing ocular dimensions in premature infants. PMID- 1513584 TI - Improvement of compensatory head postures after strabismus surgery. AB - PURPOSE: To determine the incidence and relative frequencies of orientations of compensatory head postures (CHP) and success in surgically treating the CHP seen in patients with pure lateral rectus paresis (group I), superior oblique paresis (group II), Duane syndrome (group III), Brown syndrome (group IV), and congenital motor nystagmus (group V). METHODS: The authors retrospectively reviewed all patients assessed and treated between 1985 and 1991 with these five conditions. Frequencies and orientations of the CHP were determined in all patients in each group. The success of surgery in eliminating the CHP in the subgroups of patients who underwent surgery to treat the CHP also was determined. RESULTS: The frequencies of CHP were 29.0% of 93 group I cases, 71.2% of 139 group II cases, 68.1% of 91 group III cases, 17.4% of 35 group IV cases, and all 23 group V cases, for an overall incidence of 56.7% of 381 patients. For patients who underwent surgery to eliminate a CHP, success rates were 85.7% of 21 group I cases, 75.6% of 41 group II cases, 87.2% of 47 group III cases, 100% of 5 group IV cases, and 78.3% of 23 group V patients, for an overall success rate of 82.5% of 137 surgical cases. CONCLUSION: Because CHP is seen frequently in strabismus and nystagmus disorders, ocular causes must be ruled out in any case of an anomalous head posture. Appropriately planned surgery for CHP caused by incomitant strabismus or eccentric nystagmus null zones has a high rate of success in eliminating CHP. PMID- 1513585 TI - Effects of halothane on children's electroretinograms. AB - BACKGROUND: At times, anesthesia is necessary to test children's electroretinographic (ERG) responses. Halothane, an anesthetic commonly used for pediatric patients, affects some aspects of ERG responses, but it is unknown if halothane affects ERG parameters evaluated by contemporary clinical protocols. METHODS: Scotopic and photopic ERG responses were recorded from children when awake and then under halothane. RESULTS: Halothane has no effect on scotopic b wave stimulus/response parameters, including amplitude, sensitivity, and implicit time. Scotopic a-wave amplitudes, implicit times, model parameters, and ratio of a- to b-wave amplitudes are unaffected by halothane. The amplitudes and implicit times of photopic responses to red flashes and 30 Hz flickering white light are not altered by halothane. Halothane causes no significant change in amplitudes and implicit times of the oscillatory potential wavelets. CONCLUSION: These results suggest that significant departures of ERG responses (studied with the protocol described herein) from a laboratory's normal values cannot be attributed to halothane. PMID- 1513586 TI - Magnetic resonance imaging of orbital lymphangioma with and without gadolinium contrast enhancement. AB - BACKGROUND: Lymphangioma is a vascular tumor of the orbit with a propensity for recurrent hemorrhage. These tumors may be difficult to diagnose in young patients who present with sudden proptosis due to hemorrhage into a previously unrecognized lesion. Magnetic resonance imaging (MRI) should be ideally suited for evaluating lymphangioma due to the unique ability of MRI to characterize hemorrhage because of the paramagnetic qualities of hemoglobin. METHODS: The authors performed T1-, T2-, and proton density-weighted MRI on 12 patients with orbital lymphangioma. Six patients underwent MRI with gadolinium-DTPA contrast enhancement. The MRI studies were performed using a 1.5 Tesla super-conducting magnetic resonance unit, except for 3 early studies performed with a 0.5 Tesla unit. All studies were performed with orbital surface coil imaging. Computed tomography (CT) was performed in 10 patients. RESULTS: Tumor was visible on MRI in all 12 patients. Magnetic resonance imaging delineated clearly the internal structure of subacute and chronic hemorrhagic cysts, and differentiated between these tumors because of the different paramagnetic qualities of subacute hemorrhage compared to chronic hemorrhage. In two patients, MRI detected large tumor feeding vessels by the flow void phenomenon unique to MRI. Computed tomography did not detect these vessels. Gadolinium-contrasted T1-weighted MRI did not further delineate or characterize the tumor. CONCLUSION: Magnetic resonance imaging is the modality of choice for imaging orbital lymphangioma because of its unequalled differentiation of hemorrhagic cysts, and its unique ability to detect tumor feeding vessels by the flow void phenomenon. PMID- 1513587 TI - Immunohistochemical evidence for C3bi involvement in Graves ophthalmopathy. AB - PURPOSE: To determine by immunohistochemical methods if components of the complement system are present in Graves ophthalmopathy extraocular and periocular tissues compared with non-Graves ophthalmopathy ocular tissues, and, if so, whether a qualitative difference exists. METHODS: Orbital muscle, periorbital muscle, and adipose tissue from 10 Graves ophthalmopathy patients were studied with in situ assays using monoclonal antibodies for C3bi and C5b-9 (the terminal attack complex) complement components. Extraocular muscle, periocular muscle, and adipose tissue from 12 patients treated for unrelated orbital disorders were used as controls. RESULTS: All nine Graves extraocular and periocular muscle tissues exhibited C3bi positive staining in an intense, localized oval- to spindle-shaped reaction that appeared to represent cells on a diffuse staining background of the endomysial and perimysial connective tissues with no staining of the muscle fibers themselves. Some reactivity was seen in 6 of the 12 control muscles, but this was much less intense than that of Graves ocular muscle tissue. Only two Graves muscle samples stained minimally with the monoclonal antibody for the C5b 9 terminal attack complex while none of the control muscle samples demonstrated reactivity. Orbital fat from Graves and control patients did not demonstrate any reactivity for C3bi or C5b-9. CONCLUSION: C3bi and not C5b-9 (the terminal attack complex) is present in Graves ophthalmopathy extraocular and periocular tissues in a qualitatively greater way than in control non-Graves ophthalmopathy ocular tissue. Consequently, C3bi may contribute to the pathophysiology of Graves ophthalmopathy. PMID- 1513588 TI - Keratophakia and keratomileusis: safety and effectiveness. American Academy of Ophthalmology. AB - The purpose of the Committee on Ophthalmic Procedures Assessment is to evaluate on a scientific basis new and existing ophthalmic tests, devices, and procedures for their safety, efficacy, clinical effectiveness and appropriate uses. Evaluations include examination of available literature, epidemiological analyses when appropriate, and compilation of opinions from recognized experts and other interested parties. After appropriate review by all contributors, including legal counsel, assessments are submitted to the Academy's Board of Directors for consideration as official Academy policy. PMID- 1513589 TI - A comparative histological study of the number and size of the myenteric ganglia and neurones in the fore-stomach and abomasum of grey, white and black Karakul lambs. AB - Homozygous grey Karakul lambs are born with a lethal genetic factor responsible for death at weaning age. When put on a high roughage diet under field conditions they develop distended, thin-walled rumens and sand impacted abomasa. Homozygous white Karakul lambs have a similar factor but survive for a longer period. Black Karakul lambs are not affected. The present study was undertaken to compare by image analysis the number and size of the myenteric ganglia, and the number of myenteric neurones in the walls of the fore-stomach and abomasum of 24-h-old grey, white and black Karakul lambs. One square centimetre samples were taken from analogous areas of the rumen, reticulum, omasum and abomasum of 38 embalmed Karakul lambs. Haematoxylin and eosin stained histological sections of each sample were studied with a Vids 2 Image Analyzer. One way analysis of variance indicated a significant difference between the groups regarding the number and size of the myenteric ganglia and in the number of myenteric neurones in the reticulum, rumen and abomasum. The number and size of the ganglia and the number of neurones was greatest in the black lambs and decreased progressively in the white and grey lambs. The omasum was not affected. It is suggested that the paucity of myenteric ganglia and neurones in the regions examined is instrumental in causing the lethal condition described above. PMID- 1513590 TI - Cardiotoxicity of the skin of the red-banded rubber frog, Phrynomerus bifasciatus (Smith 1847). AB - The skin of the red-banded rubber frog is said to secrete an unidentified toxin. Whole skin extract as well as HPLC fractions were tested for toxicity on viable, isolated cardiomyocytes. The skin extract and one of its fractions were shown to be cardiotoxic. Whole-cell clamping tests demonstrated that both extract and fraction interfered with the function of the potassium channels of the cardiomyocytes and that the toxic substance has an affinity for the IK, channels. Investigations are in progress to isolate and characterize the toxic substance. PMID- 1513591 TI - Experimental Albizia versicolor poisoning in sheep and its successful treatment with pyridoxine hydrochloride. AB - Five sheep developed severe nervous signs after being drenched with Albizia versicolor pod-material. Four of these sheep were treated with pyridoxine hydrochloride (a vitamin B6) when the symptoms of toxicity became life threatening. All the treated sheep recovered dramatically and completely after treatment while the untreated one died 2 h after receiving pod-material. A therapeutic dose of 20-25 mg pyridoxine hydrochloride/kg body mass given twice with an 8 h interval is the recommended treatment regimen. The route of administration will depend on the severity of symptoms. Chemical pathology and post-mortem findings are discussed. PMID- 1513592 TI - Bioactive peptides and serotonin in the gut endocrine cells of the crocodile, Crocodylus niloticus (Laurenti 1768): an immunocytochemical study. AB - Little is known about peptide-storing endocrine cells in the gut of the Nile crocodile. As in the case of other reptiles, particularly the alligator, a limited range of peptide-storing cells was found in the gut of the crocodile. They were somatostatin, glucagon, gastrin, neurotensin and pancreatic polypeptide. The topographical distribution of cells immunoreactive to somatostatin and gastrin in the gut of the crocodile is comparable to the situation in the alligator. Glucagon and neurotensin immunoreactive cells have a much wider distribution in the gastro-intestinal tract of the crocodile compared to the alligator. Cholecystokinin and bombesin cells previously reported in the small intestine of the alligator were not detected in this study. This is the first report to demonstrate pancreatic polypeptide and serotonin immunoreactivity in the gut of a crocodilian specie. PMID- 1513593 TI - Production and properties of monoclonal antibodies against African horsesickness virus, serotype 3. AB - Four polyethylene glycol-mediated cell fusions yielded a total of 23 monoclonal antibodies (McAbs) specific for African horsesickness virus (AHSV). Two recognised the major core structural polypeptide, VP7, while one each was specific for the outer capsid proteins, VP2 and VP5. The remainder co precipitated both VP2 and VP7. An inhibition ELISA and radio-immunoprecipitation revealed two types of co-precipitating McAbs, distinguishable from each other by the different relative amounts of the two proteins they precipitated. Only co precipitating McAbs reduced the size and number of plaques formed by AHSV on VERO cell monolayers, but even at low dilution did not completely abolish virus infectivity. A McAb specific for VP7 showed potential as a group-reactive diagnostic reagent since guinea pig antisera to all nine serotypes of AHSV, as well as an anti-serotype 4 horse serum and an anti-serotype 3 rabbit serum, inhibited its binding in ELISA to AHSV serotype 3. PMID- 1513594 TI - Experimentally-induced Cestrum laevigatum (Schlechtd.) poisoning in sheep. AB - Dried, milled Cestrum laevigatum plant material was drenched to 6 ewes at doses ranging from 2,5 to 10 g/kg/day for 1 to 47 days. The most noticeable clinical signs were depression, anorexia and ruminal stasis. These signs were accompanied by clinical pathological changes indicative of liver involvement such as increases in the serum activities of aspartate transaminase, lactate dehydrogenase and gamma-glutamyltransferase. Hepatosis characterized by accentuated lobulation, and centrilobular to midzonal coagulative necrosis, haemorrhage and congestion occurred in 2 of the 3 ewes given high doses of plant material. Liver lesions in the other animals included disappearance of hepatocytes and collapse of the reticulin stroma in the centrilobular areas. Spongy changes in the cerebral white matter were evident in the ewes of the high dose group. Ultrastructural changes in the liver comprised degeneration and necrosis of hepatocytes and occasionally endothelial cells, and disruption of sinusoidal walls. PMID- 1513595 TI - Afrotropical Culicoides: C. (Avaritia) loxodontis sp. nov., a new member of the Imicola group (Diptera: Ceratopogonidae) associated with the African elephant in the Kruger National Park, South Africa. AB - Culicoides (Avaritia) loxodontis sp. nov., is described and illustrated from both sexes collected in South Africa. It is the 5th species of the Imicola group of the subgenus Avaritia to be described from the Afrotropical Region, and is presently known only from the Kruger National Park where it has been collected in light-traps and reared from the dung of the African elephant (Loxodonta africana) on various occasions. A number of character states, and statistical analyses of antennal and palpal measurements, are used to separate the new species from its taxonomic congeners C. imicola Kieffer, 1913, C. pseudopallidipennis Clastrier, 1958, C. bolitinos Meiswinkel, 1989 and C. miombo Meiswinkel, 1991. It is suggested that the occurrence of the African elephant is the primary factor that determines the distribution of Culicoides loxodontis sp. nov., and that this close association, coupled with the fact that C. loxodontis sp. nov. can be locally abundant, may result in the cycling of certain arboviruses between this biting midge and the elephant. PMID- 1513596 TI - Anaplasmosis in Uganda. III. Parasitological and serological evidence of Anaplasma infection in Ugandan goats. AB - Randomly selected goat sera from north-western, central, and south-western regions of Uganda were analyzed parasitologically and serologically for evidence of anaplasmosis. Prevalence rates of 3.2% by parasitemia, 4.8% by card agglutination test, and 12.9% by DOT-ELISA combined with western blotting were established. Parasitologically positive samples were consistently serologically positive. Positive samples were all from either the north-western or south western regions of the country. Goats in these regions graze with cattle and are presumable exposed to the same tick species. There was no evidence of clinical caprine anaplasmosis, whereas bovine anaplasmosis cases are very common. Rhipicephalus evertsi was frequently observed on goats which cograze with cattle. PMID- 1513597 TI - Adult Amblyomma hebraeum burdens and heartwater endemic stability in cattle. AB - Several conclusions of importance to studies on the epidemiology of heartwater were drawn from an investigation in which the numbers of adult Amblyomma hebraeum ticks, to which a closed herd of Hereford cattle were exposed over a period of 6 1/2 years, were manipulated. With a tick Cowdria ruminantium infection rate of 3 5%, an endemically stable situation was created by dipping the herd only when an average of 10 adult male and female A. hebraeum ticks were counted on 10 animals. When the average was increased to 15 during the calving period, 97% of calves acquired a tick-mediated immunity at the age of 6 months. Because only adult ticks confined to the hindquarters are counted, this procedure is recommended as a feasible and practical guideline to stock owners wishing to determine a dipping programme that would ensure endemic stability. The indirect fluorescent antibody test gave a true reflection of the infection rate through ticks in calves 3-6 months old, but not in older animals that had been re-infected more than once. This is because on one hand antibody may persist for 2 years after withdrawal from tick exposure and on the other the artificial re-infection of cattle with a tick acquired immunity is not always followed by a rise in antibody titres and may even result in seronegativity. Four cows infected and re-infected through ticks, remained immune to challenge for 2 years after withdrawal from tick exposure. Within the confines of one farm 3 isolates of C. ruminantium that differed in pathogenicity and immunogenicity were recovered from ticks. One of these isolates was almost non-pathogenic to cattle. PMID- 1513598 TI - The effects of salt loading via two different routes on feed intake, body water turnover rate and electrolyte excretion in sheep. AB - The effect of dosing identical amounts of sodium chloride, via 2 different routes, on feed intake and water and electrolyte balance was investigated in sheep. Feed intake and plasma sodium concentrations were unaffected by salt loading, while water intake, fractional turnover of body water, plasma and urine potassium concentrations and urine sodium concentration changed significantly from control values (P less than 0.05). With a few exceptions, parameters were in general similar irrespective of the route whereby sodium chloride was administered. PMID- 1513599 TI - Description of Aegyptianella botuliformis n. sp. (Rickettsiales: Anaplasmataceae) from the helmeted guineafowl, Numida meleagris. AB - Aegyptianella botuliformis n. sp. (Rickettsiales: Anaplasmataceae) isolated from helmeted guineafowls Numida meleagris from the Kruger National Park is described. The rickettsia occurs within a membrane-bound vacuole in the cytoplasm of erythrocytes with up to 8 organisms in a mature inclusion. The initial body resembles that of Aegyptianella pullorum. The tightly packed, sausage-shaped intermediate forms are a distinctive morphological feature, seen as irregular, pleomorphic forms under light microscopy. While more larvae and nymphs of Amblyomma hebraeum and Amblyomma marmoreaum were found on the birds than larvae of an Argas sp., it is believed that the latter are the vectors of A. botuliformis n. sp. In addition to the Kruger National Park, positive blood smears were obtained from guineafowls at other localities in the Transvaal. PMID- 1513600 TI - Desipramine potentiates spinal antinociception by 5-hydroxytryptamine, morphine and adenosine. AB - The effects of pretreatment with desipramine, a selective noradrenaline (NA) uptake blocker, on spinal antinociception by 5-hydroxytryptamine (5-HT), morphine and an adenosine analog (NECA) in the rat hot-plate test were examined to determine if endogenous NA is involved in the spinal action of these agents. Desipramine, 25 mg/kg, had no significant intrinsic effect in the hot-plate test but potentiated spinal antinociception by NA and 5-HT. Potentiation was more prominent at higher doses of NA and 5-HT. Desipramine also enhanced the action of morphine and NECA, but, in these instances, the greatest enhancement occurred at lower doses. These results, in conjunction with others, suggest that 5-HT releases NA from the spinal cord while morphine and NECA interact synergistically with endogenously released NA. PMID- 1513601 TI - Comments on Boissevain and McCain, Pain, 45 (1991) 227-248. PMID- 1513602 TI - The prevalence of pain in hospitalized patients and resolution over six months. AB - Pain was assessed in 2415 randomly selected hospitalized patients. Fifty percent of the sample reported pain at the time of the interview, and 67% had experienced pain during the past 24 h. High levels of pain were more frequent in postpartum women, patients with diseases of the musculoskeletal systems and after injury or poisoning, but in all diagnostic categories there were patients whose lowest pain level in the preceding 24 h was moderate or severe. Patients who had undergone a surgical procedure during the past 7 days were more likely to report moderate or severe pain, but 21% of non-surgical patients reported moderate or severe pain. Twenty percent of those with pain reported that it had existed for more than 6 months. Patients reported significant impairment of function and distress as a consequence of pain. Use of analgesic medications was low overall and even lower for non-surgical patients. A decrease in pain over 3 weeks was predicted by pain of shorter duration, a shorter duration of hospitalization in the past year, and if a surgical procedure had been performed. None of these variables predicted pain resolution between 3 weeks and 3 or 6 months. Impairment of function did not increase with continuing pain but distress did. Medication use remained low at follow-up. The data indicate that current strategies to improve pain management need to be critically reviewed. PMID- 1513603 TI - Reversible pain and tactile deficits associated with a cerebral tumor compressing the posterior insula and parietal operculum. AB - Extensive psychophysical tests were conducted on a patient with a well circumscribed tumor located just inferior and posterior to the retroinsular cortex of the right hemisphere. Statistically significant laterality differences were observed, with the left hand exhibiting: (1) a higher mechanical pain threshold, (2) a higher heat pain threshold, (3) a greater cold pain tolerance, and (4) a poorer ability to discriminate roughness. The patient was re-examined 2.5 months after operative removal of the tumor and was found to have regained normal sensitivity in his left hand. Pre- and postoperative MRIs showed resolution of the tumor's mass effect on the retroinsular and neighboring parietal operculum, which likely included the second somatosensory cortex. This dramatic change in sensory capacity signifies an essential role for the posterior insula and parietal operculum in normal pain and tactile perception. PMID- 1513604 TI - Comparative study of the validity of four French McGill Pain Questionnaire (MPQ) versions. AB - Four different French versions of the McGill Pain Questionnaire (MPQ) have been published: 3 are MPQ translations in Canadian French and 1 (QDSA) is an MPQ reconstruction in (France) French. The aim of our work was to study the validity of these available questionnaires for use in France. The validity was evaluated by 44 French physicians. Various validity criteria were studied: item, dimension, subclass and pain descriptor intensity. A new French MPQ was also developed. Significant validity differences emerged between the different MPQ versions. This study confirms the satisfactory validity of the QDSA. The validity of the newly developed French MPQ was equal but not better than the QDSA. A 15-item short MPQ QDSA version was also developed. For studies with patients from France, it is recommended that the QDSA or the short MPQ-QDSA versions be used. PMID- 1513605 TI - The Pain Anxiety Symptoms Scale: development and validation of a scale to measure fear of pain. AB - Fear of pain has been implicated in the development and maintenance of chronic pain behavior. Consistent with conceptualizations of anxiety as occurring within three response modes, this paper introduces an instrument to measure fear of pain across cognitive, overt behavioral, and physiological domains. The Pain Anxiety Symptoms Scale (PASS) was administered to 104 consecutive referrals to a multidisciplinary pain clinic. The alpha coefficients were 0.94 for the total scale and ranged from 0.81 to 0.89 for the subscales. Validity was supported by significant correlations with measures of anxiety and disability. Regression analyses controlling for measures of emotional distress and pain showed that the PASS made a significant and unique contribution to the prediction of disability and interference due to pain. Evidence presented here supports the potential utility of the PASS in the continued study of fear of pain and its contribution to the development and maintenance of pain behaviors. Factor analysis and behavioral validation studies are in progress. PMID- 1513606 TI - Activation of normal and inflamed fine articular afferent units by serotonin. AB - In cats anesthetized with alpha-chloralose, extracellular recordings were made from fine afferent units belonging to the medial articular nerve (MAN) of the knee joint. The excitatory and sensitizing effects on articular afferents of serotonin (5-HT) applied intra-arterially close to the joint were examined. The joints were either normal or an experimental arthritis had been induced some hours before the recording session. Bolus injections of 1.35-135 micrograms 5-HT excited about 43% of group III (CV: 2.5-20 m/sec) and 73% of group IV units (CV: less than 2.5 m/sec) from normal joints. The latency was usually between 10 and 30 sec, and the duration and size of the responses were dose-dependent. Fast group III units (CV: greater than 16 m/sec) and group II units (CV: greater than 20 m/sec) were never excited by 5-HT. Repetitive administration led to pronounced tachyphylaxis of the 5-HT response. Inflammation induced an enhanced sensitivity of group III articular afferent units to close intra-arterial application of 5 HT. In particular the total duration of each response was considerably prolonged (4-10 min against 1-2 min under normal conditions). At the same time the tachyphylaxis seen under normal conditions was greatly reduced. In contrast, group IV articular afferent units did not become sensitized to 5-HT in the course of inflammation. In normal joints 5-HT did not sensitize fine afferent units for movement-induced responses. However, after inflammation, a distinct sensitization to such movements by 5-HT application could be observed both in group III and group IV fiber ranges. The sensitization had a short time course not exceeding 7 min. The tonic component of the movement-induced response was more enhanced than the phasic one. The bolus application of 5-HT led to temporary vasoconstriction of the knee joint vessels. This vasoconstriction was especially pronounced in inflamed joints and impeded the access of subsequently applied substances to the terminal regions of the afferent units under observation. It is concluded that the present results support the notion that 5-HT may participate in the mediation of pain from inflamed tissue such as an arthritic joint by exciting and sensitizing fine afferent units. During inflammation group III units are particularly sensitive to 5-HT and, thus, may carry the bulk of the 5-HT-induced nociceptive messages. PMID- 1513607 TI - Comparative United States and European trials of loracarbef in the treatment of acute otitis media. AB - Acute otitis media with effusion is one of the most common infectious diseases of childhood. Two multicenter randomized controlled clinical trials were conducted to assess the relative safety and efficacy of loracarbef and either amoxicillin/clavulanate or amoxicillin in the treatment of acute otitis media. Patients were evaluated clinically and bacteriologically at a pretherapy visit (within 48 hours of study drug administration), a posttherapy visit (within 72 hours after completion of therapy), and a late posttherapy visit (10 to 16 days after completion of therapy). In both studies, etiologic agents were assessed by tympanocentesis. In both studies patients had to have a pathogen susceptible to both study drugs to be continued in the study and declared evaluable. The first study, conducted at 24 United States centers, compared loracarbef 30 mg/kg/day in two divided doses and amoxicillin/clavulanate 40 mg/kg/day in three divided doses each for 10 days. At the posttherapy visit 124 (87.3%) of 142 evaluable loracarbef-treated patients and 130 (91.5%) of 142 evaluable amoxicillin/clavulanate-treated patients had favorable (cure or improvement) clinical outcomes (P = 0.247). Loracarbef-treated patients were significantly less likely to experience adverse events, notably diarrhea, than amoxicillin/clavulanate-treated patients (P less than 0.001). The second study, conducted at 12 European sites, compared loracarbef 30 mg/kg/day in two divided doses and amoxicillin 40 mg/kg/day in three divided doses each for 7 days. At the posttherapy visit 120 (81.1%) of 148 evaluable loracarbef-treated patients and 125 (87.4%) of 143 amoxicillin-treated patients had favorable clinical outcomes (P = 0.139). Loracarbef and amoxicillin displayed comparable safety, although vomiting appeared more frequently among patients receiving amoxicillin (P = 0.011).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1513608 TI - Loracarbef (LY163892) vs. penicillin VK in the treatment of streptococcal pharyngitis and tonsillitis. AB - A double blind, randomized clinical trial compared loracarbef (LY163892) with penicillin VK. Two hundred thirty-three pediatric patients (less than or equal to 12 years) with a diagnosis of pharyngitis or tonsillitis resulting from Group A beta-hemolytic streptococci were randomized to treatment. Patients in the loracarbef group (n = 120) received loracarbef as a 15-mg/kg/day oral suspension or 200-mg capsule taken twice daily for 10 days. Patients in the penicillin group (n = 113) received penicillin VK as a 20-mg/kg/day oral suspension or 250-mg capsule taken four times daily for 10 days. Successful clinical responses were demonstrated in 101 of the 104 (97.1%) evaluable patients treated with loracarbef compared with 83 of 88 (94.3%) of evaluable patients treated with penicillin. The clinical relapse rate for the loracarbef group was 2.9% vs. 5.7% for the penicillin group. Bacteriologic response data approximated the clinical response data, as eradication of Group A beta-hemolytic streptococci was found in 86.5 and 81.8% of the loracarbef group and the penicillin group, respectively. No statistically significant difference in the incidence of treatment-emergent adverse reactions was noted between the two groups. The results indicate that loracarbef taken twice daily was comparable in safety and efficacy to penicillin VK taken four times daily in the treatment of Group A beta-hemolytic Streptococcus-associated pharyngitis and tonsillitis in children. PMID- 1513609 TI - Loracarbef vs. cefaclor in pediatric skin and skin structure infections. AB - A double blind, randomized clinical trial involving 214 children, ages 6 months to 12 years, compared the safety and effectiveness of the new carbacephem loracarbef and the cephalosporin cefaclor for the treatment of skin and skin structure infections. The two agents were given primarily as oral suspensions. Dosages were 15 mg/kg/day in two divided doses for loracarbef and 20 mg/kg/day in three divided doses for cefaclor. Assessment 72 hours after completion of the 7 day course of treatment indicated a favorable clinical response plus eradication of the pretherapy pathogen in 97.3% of the 74 loracarbef-treated patients eligible for evaluation and 92.3% of 78 evaluable cefaclor-treated patients. Favorable response rates at a second posttreatment visit 10 to 14 days after the end of therapy were 95.6% in 68 evaluable loracarbef-treated patients and 86.2% in 65 treated with cefaclor. The incidence of adverse reactions, including gastrointestinal effects, was low in both groups. No statistical difference in clinical or bacteriologic efficacy or safety was detected between patients treated with loracarbef and cefaclor. PMID- 1513610 TI - Infectious diseases and child day care. AB - It is estimated that more than 5.3 million children attend out-of-home child day care in the United States. This includes 2.1 million children who attend approximately 63,000 licensed child day-care centers. An additional 500,000 children receive care in 105,000 regulated day-care homes. Since the total regulated child care slots available in centers and homes are only 2.6 million, some 2.7 million additional children are likely attending unregulated family day care homes. As a result infants and preschool children are intermingled in child care facilities that often lack adequate toilet and hand-washing facilities and are frequently staffed by individuals with little or no training in the area of infection control. Placing children in out-of-home care should not compromise their health and that of the community. The risk of infection can be lessened by teaching hygiene, supervising unregulated day-care facilities and regular antibiotic use so that bacterial resistance may be prevented. PMID- 1513611 TI - Ten-year review of otitis media pathogens. AB - Data collected from 1980 to 1989 by investigators at the Pittsburgh Otitis Media Research Center were examined to detect changes over time in the prevalence of bacteria isolated from middle ear effusions in patients with otitis media. The organisms isolated most commonly from the 7396 effusions cultured at the center were Streptococcus pneumoniae and Haemophilus influenzae. S. pneumoniae predominated in the subgroup of patients with acute otitis media, whereas H. influenzae was isolated most frequently from patients with otitis media with effusion. The most notable changes to occur during the 10-year period were a statistically significant increase in the prevalence of S. pneumoniae in patients with acute otitis media and a progressive rise in the percentage of beta lactamase-producing strains of H. influenzae and Moraxella (Branhamella) catarrhalis. The latter finding suggests the need for therapeutic alternatives to amoxicillin, which is not active against beta-lactamase-producing organisms, when these organisms are suspected or cultured from the middle ear. PMID- 1513612 TI - Temperament and the psychobiology of childhood stress. AB - This paper provides a conceptual overview of recent research on the developmental psychobiology of childhood stress. We propose that the construct of temperament can be regarded as an organizing principle in children's responses to environmental adversity, and we review three physiologic "windows" through which such responses can be usefully examined. It is concluded that individual differences between children in their psychobiologic reactivity to stressors may constitute an important and novel point of departure for future studies of stress and childhood morbidity. PMID- 1513613 TI - Individual differences in response to stress. AB - Observation of newborns and infants reveals individual differences in reactivity to stress. A measurement system based on threshold, dampening, and reactivation is described to assess these individual differences in the newborn period and thereafter. The three features are independent and, therefore, represent different aspects of reactivity. There is some evidence for stability of individual differences in reactivity between birth and 2 months of age. This stability is more apparent for infants who were highly reactive as newborns. The role of dispositional factors of reactivity, their stability, and the effects of the environment are discussed. PMID- 1513614 TI - Reactivity of the hypothalamic-pituitary-adrenocortical system to stressors in normal infants and children. PMID- 1513615 TI - Vagal tone: a physiologic marker of stress vulnerability. AB - Vagal tone is proposed as a novel index of stress vulnerability and reactivity with applications in all branches of medicine, and with particular value in pediatrics. The paper proposes a model emphasizing the role of the parasympathetic nervous system and particularly the vagus nerve in mediating homeostasis and defining stress. Measurement of cardiac vagal tone is proposed as a method to assess on an individual basis both the stress response and the vulnerability to stress. The method monitors the neural control of the heart via the vagus (ie, vagal tone) as an index of homeostasis. The method provides a standard instrument with statistical parameters that are comparable between patients and throughout the life span. This noninvasive method will allow the assessment of the stressful impact of various clinical treatments on the young infant and permit the identification of individuals with vulnerabilities to stress. PMID- 1513617 TI - Behavior, biology, and the meanings of temperamental constructs. PMID- 1513616 TI - Early rearing conditions alter immune responses in the developing infant primate. AB - The influence of early rearing conditions on immunologic development was investigated in infant monkeys. Lymphocyte proliferation, natural killer cell activity, and antibody responses to tetanus vaccination were compared in 30 rhesus monkeys reared under five different conditions. Lymphocyte responses to two mitogens (concanavalin A and pokeweed) were significantly increased in infants from disturbed rearing conditions compared with control infants that had been reared in an undisturbed manner by their mothers. The largest increases occurred in nursery-reared monkeys that had been fed Similac infant formula. The nursery-reared monkeys also tended to show lower natural killer cell activity, but there were no significant differences in response to vaccination. These findings support other research indicating that psychologic and nutritional aspects of the early rearing environment may have long-lasting effects on some, but not all, immune responses in the developing infant. PMID- 1513618 TI - [The screening assessment of the burden of hereditary anamnesis and its significance in the prognosis of acute morbidity of children after entering a preschool institution]. PMID- 1513619 TI - [State of excretory and incretory function of the pancreas in acute intestinal infections in young children]. PMID- 1513620 TI - [Clinico-bacteriological characteristics of uro-renal infection in young children]. PMID- 1513621 TI - [Relations between local and general immunity in children with chronic viral hepatitis]. PMID- 1513622 TI - [Clinico-metabolic adaptation of the fetus in maternal obesity]. PMID- 1513623 TI - [Breast milk as a source of hormones possessing antioxidant activity]. PMID- 1513624 TI - [Incidence of acute pneumonia at the pediatric unit and ways of improving its diagnosis]. PMID- 1513625 TI - [Role of oxygen transport function of blood in the pathogenesis of segmental pneumonia in young children]. PMID- 1513626 TI - [State of hemostasis in hemorrhagic vasculitis in children]. AB - The purpose of the study was to explore hemostasis in children suffering from hemorrhagic vasculitis (HV) by means of the new amidolytic methods using chromogenic substrates. The patient's plasma was studied for the content of thrombin, trypsin, factor Xa, AT-III, kallikrein, plasmin, free heparin, urokinase, factor 3 of platelets, prothrombin and Willebrand's factor. 69 children with HV were entered into the study. All of them were examined during crises. In cutaneous HV, the content of trypsin decreased 3-fold, the content of factor Xa increased 5-fold; there was a negligible increase in the plasmin and AT III levels; the content of kallikrein rose 2-fold, that of urokinase 60-fold; the release of platelet factor 3 was intensified 1.5-fold, the activity of prothrombin 3-fold. These data indicate that in cutaneous HV, blood coagulation increased. However, the signs of disseminated intravascular coagulation were lacking because of the high blood anticoagulant activity. In mixed HV, the phase of hypercoagulation was not made for by the blood anticoagulant activity, since the latter one was depleted. The capillary toxic nephritis may give rise to disseminated intravascular coagulation associated with the depletion of the anticoagulant component. The gravity of HV and its complications can be predicted according to the characteristics of the anticoagulant component of hemostasis, especially according to the levels of urokinase and AT-III. PMID- 1513627 TI - [Histiocytic proliferative diseases in children]. AB - The course of histioproliferative diseases was analyzed in 308 children treated at the All-Union Cancer Research Center, USSR AMS. Of these, there were 8 children with benign proliferation (Rosai-Dorfman disease). Histiocytosis-X was revealed in 232 children. The authors describe the regularities of histiocytic proliferation manifestations depending on the patients' age. Provide morphological (cytological) criteria for different types of histioproliferative diseases and characterize the treatment data. PMID- 1513628 TI - [State of the reproductive function in women who had lymphogranulomatosis in childhood and adolescence]. AB - As many as 33 women who received combined treatment (fully successful) at an age of 5-26 years for lymphogranulomatosis were examined. In 30 patients, the structure and function of the reproductive organs was within age norm. In 20 women, there were 20 deliveries at an age of 19-33 years, with the mean age amounting to 23 years; 10 boys and 10 girls were born. The children are healthy. The selective toxicity of the treatment as a whole and of each of its components with regard to the reproductive organs was not proved. In the authors' opinion, two cases of disease relapses in pregnant women do not form basis for recommending the woman do refrain from pregnancy in the long-term periods after the treatment of lymphogranulomatosis. PMID- 1513629 TI - [Characteristics of immunobiological resistance of children with diabetes mellitus]. AB - Immunoglobulins and nonspecific defence factors (complement, properdin, lysozyme) were studied over time in 194 children suffering from diabetes mellitus. In 145 children, diabetes mellitus was associated with chronic tonsillitis. Resistance in 49 children was examined depending on the phase of diabetes mellitus. The data obtained indicate that diabetes mellitus is marked by imbalance of nonspecific defence factors and humoral immunity. These changes are obviously related to the disease gravity, phasic nature of the process, diabetes mellitus standing, and the presence of concomitant diseases. No parallelism was established between the level of nonspecific defence factors and specific immunity activity. PMID- 1513630 TI - [Hormonal-metabolic disorders in children with diabetes mellitus in the preclinical stage of diabetic retinopathy]. AB - A relationship was established between alterations in vessels of the fundus of the eye and diabetes mellitus standing, the character of metabolic disorders, hereditary load with regard to cardiovascular diseases. The risk factors of the development of the preclinical stage of diabetic retinopathy are as follows: hereditary load with regard to cardiovascular diseases, parship, an increase of the content of lactate, a reduction of the content of 2,3 diphosphoglycerophosphate, a rise of the content of glycosylated hemoglobin, high content of cholesterol esters in red blood cell membranes, of free cholesterol and malonic dialdehyde in blood serum, a decline of the level of phospholipids and a rise of cardiolipin content in red blood cell membranes, and increase of blood serum cortisol. PMID- 1513631 TI - [State of the renin-angiotensin system in children with different clinical variants of congenital adrenal cortex hyperplasia caused by 21-hydroxylase deficiency]. AB - A study was made of plasma renin activity (PRA) and serum aldosterone (A) in 52 children with congenital hyperplasia of the adrenal cortex due to 21-hydroxylase deficiency. There were 40 girls and 12 boys aged 1.5 months to 14 years. Of these, 35 had the salt-losing form (group 1), 12 were with a simple virile form (group 2), and 2 with the typical disease form (group 3). By the moment of the first examination the majority of the group 1 patients had received glucocorticoids (GC) combined with mineralocorticoids (MC), group 2 had been given GC alone, and the group 3 children had been untreated. Initially PRA in both the first and second groups was higher than in the controls. However, in group 2 that difference was insignificant. The concentration of A in group 2 noticeably exceeded that in the controls and group 1. In group 3, PRA and A did not differ from normal. After the treatment was potentiated by MC (including MC administration to the group 2 patients) there was a decline of PRA and of the A level. The changes in PRA and A did not often manifest clinically and were not associated with electrolyte disturbances. In the authors' opinion, to choose adequate doses of MC, it is necessary to examine PRA and blood A level. PMID- 1513632 TI - [Aid to the physician in monthly correction of infant nutrition at the pediatric section]. PMID- 1513633 TI - [Clinico-epidemiological and laboratory features of delta infection in children with viral hepatitis]. PMID- 1513634 TI - [Diagnosis of prostatitis in children]. PMID- 1513635 TI - [Clinico-immunological characteristics in children given meningococcal group A polysaccharide vaccine developed at the G. N. Gabrichevski Moscow Research Institute of Epidemiology and Microbiology]. PMID- 1513636 TI - [Analysis of qualimetric control of pediatrician's knowledge]. PMID- 1513637 TI - [Role of renal dysembryogenesis in the development of nephropathies]. PMID- 1513638 TI - [Tactics of adjuvant therapy in the treatment of acute lymphoblastic leukemia according to the BFM program]. PMID- 1513639 TI - [Characteristics of the morphology of peripheral blood erythrocytes of healthy children 1 to 6 years of age (scanning electron microscopy data)]. AB - The authors provide classifications of the forms of peripheral red blood cells examined by scanning electron microscopy (SEM). The authors' working classification is presented in which the following types of red blood cells are distinguished: discocytes; transitory, namely, echinocytes, stomatocytes, spheroids; spherocytes, reticulocytes, deformed, target-like, bifoveal hypochromic, elliptocytes, destructive. SEM was used to study capillary blood red blood cells in 30 healthy children aged 1 to 6 years. The ratio of the morphological types of red blood cells in this group children is presented. PMID- 1513640 TI - [Problems in raising healthy children and formation of healthy life styles of the younger generation]. PMID- 1513641 TI - [Familial erythrophagocytic lymphohistiocytosis]. PMID- 1513642 TI - [Primary multiple neuroblastoma in a child]. PMID- 1513643 TI - [Biological role of lactoferrin and its significance in infant feeding]. PMID- 1513644 TI - [Immunological aspects of food intolerance in children during first years of life]. AB - A study was made of the morphofunctional status and local defence of the gastrointestinal tract in 122 children aged 4 months to 6 years, suffering from food intolerance showed up by atopic dermatitis in 52 children and by chronic diarrhea in 70 children. Based on the allergological anamnesis, scarification cutaneous tests with food allergens, detection of antibodies to food antigens (RAST, HAIT) food allergy was revealed in all the children. Chronic gastroduodenitis was identified in all the children suffering from atopic dermatitis and in 95% of the children with chronic diarrhea. It should be mentioned that one-third of that group had a graver illness--diffuse duodenitis with sub-atrophy of the villi. The allergic genesis of the impairment of the gastroduodenal mucosa was confirmed. It was more remarkable in atopic dermatitis (tissue eosinophilia and high content of IgE-plasmacytes in the duodenal mucosa). The decrease of local immune defence of the mucous membrane, lactase deficiency, elevated growth of microorganisms in the duodenal contents promote the rise of intestinal barrier permeability for food antigens and enhancement of sensitization. PMID- 1513645 TI - [Characteristics of the functional state of the pancreas, lipid peroxidation and antioxidant defense in food hypersensitivity in children]. AB - Pancreas function, lipid peroxidation and antioxidant defence were studied in 154 children aged 1 to 14 years with food allergy. Allergic inflammation due to food allergy favours the origin of different abnormalities of pancreas function: functional (39.4%), reactive pancreatitis (31.3%), chronic pancreatitis (20.1%), and sclerosing chronic pancreatitis (9.2%). They occur in combination with lipid peroxidation activation and a decrease in antioxidant defence. The intensity of the latter ones is dependent on the variety of pancreas function disturbance. The most significant changes in lipid peroxidation and antioxidant defence were discovered in chronic pancreatitis. PMID- 1513646 TI - [Bronchial asthma in children with sensitization to mites]. AB - Overall 180 children with bronchial asthma induced by sensitization to Dermatophagoides pteronyssinus and Dermatophagoides farinae were examined clinically and immunologically. The patients' age ranged from 1 to 14 years. A relationship was established between bronchial asthma exacerbation and the stay at home. In that disease pattern, asphyxia attacks were noted to occur more frequently in the evening and night hours. Emphasis is laid on the leading part played by the IgE-mediated mechanism in bronchial asthma induced by tick-borne sensitization. In children suffering from that pattern of bronchial asthma, specific hyposensitization with Dermatophagoides pteronyssinus allergens and antiallergic immunoglobulin were found to be highly effective. PMID- 1513647 TI - [Allergies in children with metabolic nephropathies]. AB - The authors describe the results of the follow-up of children of the early age (n 68) and senior age (n-42) with different allergic diseases and 77 children with metabolic nephropathies (oxalate nephropathy, pyelonephritis associated with metabolic disorders, interstitial nephritis). In both age groups, an interrelationship was established between renal pathology in the form of metabolic nephropathies and allergo-pathology. Children with different allergies manifested the high incidence of metabolic disorders, with crystalluria and erythrocyturia being mostly encountered in respiratory allergies whereas leukocyturia largely occurred in skin allergies. At the same time the high incidence of allergic reactions was revealed in children with metabolic nephropathies. A relationship was established between the signs of atopy with graver varieties of nephropathies. The presence of the common pathogenetic components in the development of allergic and renal pathology requires the inclusion of immunologic and nephrologic methods into the complex of those patients' examination and the consideration of those factors in the treatment policy. PMID- 1513649 TI - [Subpopulation state of T and B lymphocytes in hemolytic-uremic syndrome in children]. AB - A study was made of the quantitative characteristics of T and B lymphocytes and of their subpopulations (A-RFC; E37-RFC; auto-RFC; EAC-RFC; Ig(+)-cells) as well as of 0-lymphocytes in the peripheral blood of 20 children aged 6 to 24 months with different clinical stages of the hemolytic-uremic syndrome (oligoanuria, diuresis onset, polyuria, clinical improvement). It is concluded that all the stages of the disease are characterized by the deficiency of certain subpopulations of T cells (especially A-RFC, E37-RFC), B lymphocytes, and 0 cells. By the moment of the clinical improvement, the cellular characteristics of the immune status do not return to normal. PMID- 1513648 TI - [The state of the immune system in children with congenital abnormalities]. AB - As many as 618 children with different varieties of congenital developmental abnormalities were examined for the status of the immune system. Immunologic studies were carried out in 89 patients. They included the NBT test, determination of the content of T-, B- and O-lymphocytes, IgA, IgM and IgG. Morpho-histological studies of the spleen and thymus were performed according to the data of 529 autopsies. It has been established that 3/4 of cases with congenital developmental abnormalities are characterized by morphofunctional immune deficiency, which is more pronounced in multiple abnormalities (of chromosomal etiology in particular) as well in some systemic abnormalities, largely of the CNS. PMID- 1513650 TI - [Chlamydia infection syndrome in mother and the newborn]. PMID- 1513652 TI - [Causes of death at home of infants under 1 year of age in a rural location (according to the records of the Republic of Kirghizstan)]. PMID- 1513651 TI - [Clinical features of juvenile rheumatoid arthritis with onset before 5 years of age]. PMID- 1513653 TI - [Methods of training students of a pediatric department in tuberculosis control at a children's polyclinic]. PMID- 1513654 TI - [Lingering diarrheas in infants and young children]. PMID- 1513655 TI - [Mucoviscidosis (experience with a follow-up of 222 patients during 38 years of pediatric practice)]. PMID- 1513656 TI - [Clinico-social aspects of the evaluation of health status of children attending preschool institutions]. PMID- 1513657 TI - [Rehabilitation of children with diseases of the respiratory organs in preschool general somatic sanatoria]. PMID- 1513658 TI - [Current problems of allergology in children]. PMID- 1513659 TI - [A case of secondary insufficiency of phagocytosis function in a newborn infant with Pelger's neutrophil anomaly]. PMID- 1513660 TI - [Significance of immune and endocrine systems in the pathogenesis of suppurative meningitis in infants and young children]. PMID- 1513661 TI - [Nonhospital mortality of children]. PMID- 1513662 TI - [Evaluation of the analgetic effect of electropuncture using cardiointervalography indicators in children in the postoperative period]. PMID- 1513663 TI - Is science bad for the soul? PMID- 1513665 TI - The perceived duration of gratings. AB - Since visible persistence of grating patterns increases with spatial frequency, it is often inferred that the perceived duration of a grating is also longer at higher spatial frequencies. However, other work has demonstrated that the perceived onset of a grating is also delayed at higher spatial frequencies. Thus it is impossible to infer the subjective duration from the results of visible persistence studies alone. In order to estimate perceived duration in the present study, reaction times (RTs) to grating onsets and offsets were measured for a range of spatial frequencies. The results indicate that although the perceived duration (ie the difference between offset and onset RTs) was consistently longer than the physical duration, the estimates of perceived duration did not vary with changes in spatial frequency. Differences between the present results and earlier findings are interpreted in the context of the different methods used to measure perceived offset. PMID- 1513664 TI - Temporal integration of spatially filtered visual images. AB - Factors which govern the temporal integration of spatial information were examined in a group of five experiments. A series of high-pass and low-pass spatially filtered versions of a visual scene were generated. Observers' ratings of these filtered versions of the scene for perceived image quality indicated that quality was determined both by the bandwidth of spatial information and the presence of high-spatial-frequency edge information. When sequences of three different versions of the scene were presented over an interval of 120 ms the perceived quality of the resulting composite image was determined both from the ratings of the individual components of that sequence and from the order in which these components were presented. When the order of spatial information in a sequence moved from coarse to fine detail the perceived quality of the composite image was significantly better than when the order moved from fine to coarse. This evidence of a coarse-to-fine bias in pattern integration was further investigated with a detection paradigm. The pattern of errors once again indicated that temporal integration of spatial information was superior when a coarse-to-fine mode of information delivery was employed. Taken together the data indicate that the pattern-integration mechanism has an inherent order bias and does not accumulate spatial information so efficiently when the 'natural' coarse to-fine order is violated. PMID- 1513666 TI - Anatomy of a flash. 2. The 'width' of a temporal edge. AB - In a previous study it has been found by using the Crawford masking paradigm with spatially coextensive stimuli that the end points of even a weak flash have a strong masking effect on the probe pulse, but no threshold elevation was observed when the probe was 100 ms or longer from flash onset and offset. The relationship between the strength of a temporal edge (eg the amplitude of a sudden increase in field luminance) and the duration of masking has not been systematically investigated. In the present experiments the duration of masking produced by a step of luminance as a function of step size was measured. With steps whose amplitude was between ten and five hundred times detection threshold, the duration of masking was about constant, ie 70 and 50 ms for on-responses and off responses, respectively. This refractory period defined the 'width' of a temporal edge. Unless two suprathreshold unidirectional luminance changes are separated by an interval exceeding the width of a temporal edge, they are perceived as a single change in brightness. A linear systems analysis led to predictions for ramp stimuli that were confirmed by experiment. PMID- 1513667 TI - Illusory occluding contours and surface formation by depth propagation. AB - A novel kind of depth-spreading effect which should be distinguished in various aspects from the known interpolation, averaging, or 'filling-in' phenomena is reported. The demonstrations and experiments suggest that depth from an uncrossed disparity can be extrapolated from, not just interpolated between, illusory or real contours to form perceptually a background surface. In addition, the form of the illusory contour itself could be drastically changed in configuration and sharpness, contingently with perceptual background-surface formation. No such effects of surface and contour formation were observed in the crossed disparity case. Because the illusory contours were enhanced and perceived as illusory 'occluding contours', these effects may be closely related to the 'occlusion constraints' in the real world. PMID- 1513668 TI - Cooperative representation of visual borders. AB - Recently it has been reported that the visual cortical cells which are engaged in cooperative coding of global stimulus features, display synchrony in their firing rates when both are stimulated. Alternative models identify global stimulus features with the course spatial scales of the image. Versions of the Munsterberg or Cafe Wall illusions which differ in their low spatial frequency content were used to show that in all cases it was the high spatial frequencies in the image which determined the strength and direction of these illusions. Since cells responsive to high spatial frequencies have small receptive fields, cooperative coding must be involved in the representation of long borders in the image. PMID- 1513669 TI - Anomalous spiral aftereffects: a new twist to the perception of rotating spirals. AB - Stationary spirals viewed after inspecting rotating sectored disks appear to rotate and to expand or contract radially, even though the rotating disks contain no perceptible components of radial motion. Moreover, the relative directions of illusory rotation and radial motion observed in these instances are 'impossible' under the stimulus constraints normally imposed by the geometry of a spiral under rotation: the stationary spirals appeared to expand/contract in directions opposite to those normally observed under conditions of actual spiral rotation, and under conditions of illusory spiral rotation in classical spiral aftereffects. PMID- 1513670 TI - Movement and proximity constrain miscombinations of colour and form. AB - A relatively frequent error when reporting brief visual displays is to combine presented features incorrectly. It has been proposed that Gestalt grouping constrains such errors so that miscombined features tend to come from the same perceptual group. In three experiments it was examined whether this principle applies to grouping by motion, and to grouping by proximity. Miscombinations of colour and form were more likely to consist of a colour and form that had moved in the same direction than features which had moved in opposite directions. Miscombinations were also more likely for adjacent items. The implications of these results for the mechanisms of feature integration are discussed. PMID- 1513671 TI - Vision with equiluminant colour contrast: 2. A large-scale technique and observations. AB - A simple technique is described for producing large-scale, tritanopic displays. The technique reproduces the various phenomena of vision with equiluminous-colour contrast that have previously been reported with red/green stimuli. It is, however, much less demanding technically, robust against artifacts, and can be used on large-scale scenes. One advantage of the technique is that a piece of blue filter can be used individually by each observer to compare quickly tritanopic and luminance conditions. PMID- 1513672 TI - Learning to see random-dot stereograms. AB - In the present study some specific properties of the learning effects reported for random-dot stereograms are examined. In experiment 1 the retinal position specific learning effect was reproduced and in a follow-up experiment it was shown that the position specificity of learning can be accounted for by selective visual attention. In experiments 2 and 3 evidence was obtained that suggests that observers can learn, to a certain degree, monocular random-dot patterns and that this learning facilitates the depth percept. This result indicates that the traditional belief that random-dot stereograms are devoid of monocularly recognizable or useful forms should be reconsidered. In the second set of experiments the learning of two binocular surface properties of random-dot stereograms, depth edges and internal depth regions, was investigated. It was shown in experiment 4 that the depth edges of random-dot stereograms are not learned, whereas the results of experiment 5 indicate that the internal depth regions are learned. Finally, in experiment 6 it was shown that depth edges are learned when the internal depth regions of the stereogram are ambiguous. The results are discussed in terms of the importance of the particular type of stimulus used in the learning process and in terms of perceptual learning and attention. PMID- 1513673 TI - Use of a distracting task to obtain defensive head movements to looming visual stimuli by human adults in a laboratory setting. AB - Defensive responses to looming visual stimuli have been obtained in a wide variety of species, including human infants as young as one week. This phenomenon has not, however, been formally demonstrated for adults under laboratory conditions. In this paper it is reported that similar responses, namely avoidance movements of the head, can be obtained in most human adults provided that they are suitably distracted by playing a computer tracking game. Such behaviours were not obtained when subjects were not so distracted. The use of control conditions also ruled out the possibility that simple movement cues from stimuli presented on a noncollision trajectory are sufficient stimulus to obtain defensive responses. It is of interest to note that latencies for avoidance movements were significantly shorter than those for orienting movements in the same situation, but were no different from the latencies for orienting movements when subjects were not distracted. It is argued that these findings are consistent with the proposition that defensive head movements to looming stimuli, like orienting movements to novel peripheral stimuli, represent a basic visual competence that is normally suppressed (or subsumed) by higher competences. The decision to avoid is probably based on the computation of time to contact, and may reflect the operation of a subcortical system for elementary analysis of optic flow. PMID- 1513674 TI - The apparent shape of afterimages in the Ames room. AB - When observers project afterimages of circular patterns onto a surface slanting away from them the images are reported as being oval in shape. In this paper it is reported that this does not occur when similar afterimages are projected onto the slanting rear wall of an Ames room. Instead of appearing as ovals, the afterimages remain circular. It appears as though the actually-slanted rear wall of the room not only looks as if it is normal to the line of vision, but also that it functions as if it was in such an orientation as far as a projection surface for afterimages is concerned. While these results are consistent with Emmert's law and with traditional accounts of shape and size constancy, they raise once again the age-old issue of whether the 'image on the retina' constitutes an object of perception that can be described in terms of its shape or size. PMID- 1513675 TI - The Muller-Lyer illusion Mark II. AB - A new illusion of size is described. A passage of print occupying about half a standard A4 sheet appeared larger than the same passage when the sheet was cropped immediately above and below it. This illusion is demonstrated and explained in terms of perceptual compromise between the vertical extent of the printed passage and the sheet of which it is an intrinsic feature. In this sense it is held to be essentially the same as the Muller-Lyer illusion of extent in which the spaces between the apexes are intrinsic to the figure. PMID- 1513676 TI - The original of E G Boring's 'young girl/mother-in-law' drawing and its relation to the pattern of a joke. PMID- 1513677 TI - A methodological comment in response to Hepper (1988) PMID- 1513678 TI - Should intracerebroventricular nerve growth factor be used to treat Alzheimer's disease? PMID- 1513679 TI - The discovery of the cardiac conduction system: the testimony of the authors. PMID- 1513680 TI - Human HIV vaccine trials: does antibody-dependent enhancement pose a genuine risk? AB - Antibody-dependent enhancement is a general in vitro property of enveloped viruses. In certain circumstances, antibody-dependent enhancement is a bona fide pathophysiologic mechanism in vivo. There are several examples of virus disease of humans and animals in which incomplete or partial immunity can lead to enhanced infection and/or disease. In some cases, this appears to be attributable to antibody-dependent enhancement. Conversely, there are several examples of viruses for which in vitro antibody-dependent enhancement has been demonstrated, but for which vaccines have been used safely in millions of persons for decades. Finally, antibody-dependent enhancement of HIV is a genuine concern. However, to date there is no direct clinical, experimental, or epidemiological evidence that HIV enhancement can be operative in vivo. Such evidence should be actively sought. PMID- 1513681 TI - A theory of the mind/brain dichotomy with special reference to the contribution of positron emission tomography. PMID- 1513682 TI - Responses of the health professions to the demographic revolution: a multidisciplinary perspective. PMID- 1513683 TI - Myasthenia, Elise Borden, and me. PMID- 1513684 TI - Baccalaureate and master's degree programs in nursing accredited by the NLN 1992 93. PMID- 1513685 TI - Practical nursing programs accredited by the NLN. 1992. PMID- 1513687 TI - Power to the patients. PMID- 1513686 TI - Smart moves in Zagreb. PMID- 1513688 TI - Pick and mix. PMID- 1513689 TI - School for health. PMID- 1513690 TI - Milk shake-up. PMID- 1513691 TI - Welcome developments. PMID- 1513692 TI - Sexuality matters. PMID- 1513693 TI - Skill muddle? PMID- 1513694 TI - More input required. PMID- 1513695 TI - Cost-effective care. PMID- 1513696 TI - Action on Ashworth. PMID- 1513697 TI - Improving domiciliary terminal care. PMID- 1513698 TI - Taking on Alfie. PMID- 1513699 TI - A measure of South Africa's health care. PMID- 1513700 TI - Intuitive actions. PMID- 1513701 TI - Paganism. PMID- 1513702 TI - Quality feat. PMID- 1513703 TI - The great outdoors. PMID- 1513704 TI - Systems of life quiz. PMID- 1513706 TI - Respite choice. PMID- 1513705 TI - A short break. PMID- 1513707 TI - Health visiting revisited. PMID- 1513709 TI - Lightening risks. PMID- 1513708 TI - A damning report. PMID- 1513710 TI - Slipping through the net. PMID- 1513711 TI - Life on hold. PMID- 1513712 TI - Pregnant pause. PMID- 1513714 TI - Profit before people? PMID- 1513713 TI - Testing ground. PMID- 1513715 TI - Freedom to care. PMID- 1513716 TI - The quiet menace. PMID- 1513717 TI - Do we need research? PMID- 1513718 TI - In danger of extinction? PMID- 1513720 TI - Combining talents. PMID- 1513719 TI - Family values. PMID- 1513721 TI - Testing alcohol wipes. PMID- 1513722 TI - To clean or not to clean? PMID- 1513723 TI - Handwashing practices. PMID- 1513724 TI - Making post-mortems safe. PMID- 1513725 TI - Intraosseous versus intravenous epinephrine infusions in lambs: pharmacokinetics and pharmacodynamics. AB - Intraosseous and intravenous administrations of epinephrine were compared in newborn lambs. Plasma epinephrine levels were measured during each route of drug administration and used to calculate steady-state epinephrine clearance rate and to compare cardiovascular responses with plasma levels. Epinephrine was administered at a dose of 0.5 to 5 micrograms/kg/min. We observed first-order (linear) clearance kinetics by both routes of drug administration. The plasma epinephrine clearance rate was 186 +/- 17 ml/kg/min by the intraosseous route versus 174 +/- 11 ml/kg/min by the intravenous route. Dose responses were analyzed by computerized fit to a threshold model. The plasma epinephrine threshold, or lowest plasma level beyond which discernible increases in blood pressure occur, was slightly lower after intravenous than after intraosseous drug administration, 2.0 +/- 0.6 ng/ml versus 4.0 +/- 0.9 ng/ml of epinephrine. Both thresholds were within the ranges of plasma epinephrine levels that would be achieved at doses of 0.4 to 0.6 microgram/kg/min by either route. Other hemodynamic responses, including the maximum systolic blood pressure and degree of reflex bradycardia, were comparable. These results support the effectiveness of the intraosseous route for epinephrine administration. PMID- 1513726 TI - The use of nebulized albuterol in wheezing infants. AB - Using a double-blind, placebo-controlled protocol, we evaluated the efficacy of nebulized albuterol in the treatment of infants aged 0 to 24 months who presented to the emergency department with wheezing. Twenty-five infants were randomly assigned to receive two identical treatments of either nebulized albuterol (0.15 mg/kg) or placebo (saline). Assessment after each treatment included a wheeze and retraction score, respiratory and heart rates, and pulse oximetry. After two treatments, there was a significant improvement in the wheeze scores (P less than 0.05) and total scores (P less than 0.05) of the albuterol group compared with the placebo group. After one treatment, there was an initial decrease in oxygen saturation in the albuterol group, which improved after the second treatment. There were no significant differences between the two groups in heart rate or respiratory rate. This study supports the use of nebulized albuterol in the treatment of wheezing infants in the emergency department. PMID- 1513727 TI - Review of 180 episodes of chest pain in 134 children. AB - This study intends to establish the etiology of chest pain in the pediatric population, to determine the causal relationship between a cardiac problem and chest pain in acutely sick children, and to provide a systematic approach to the management of these patients. The charts of 134 patients, up to 19 years of age, seen in the emergency department (ED) of Children's Hospital of Wisconsin (CHW) with the primary diagnosis of "chest pain" during a five-year period were reviewed. In 15% of these patients, a relationship was established between chest pain and actual cardiac disease. A thorough history and physical examination are the diagnostic "keys" in evaluating pediatric patients with chest pain; laboratory tests are often helpful when indicated by the history and physical examination. In the majority of the cases, reassurance is all that is required; occasionally, pharmacologic treatment is recommended. Hospitalization is rarely necessary. PMID- 1513728 TI - Prophylactic oral antibiotics for low-risk dog bite wounds. AB - The use of prophylactic antibiotics in the initial treatment of noninfected dog bite wounds is controversial. All patients with noninfected dog bite wounds who presented to our emergency department (ED) over a two-year period were considered for entry into a randomized prospective study. Patients were excluded from the study if they had any high-risk criteria for infection: puncture wounds, hand or foot wounds, wounds greater than 12 hours old, a history of immunocompromising disorders, or the use of immunosuppressive drugs. Patients in the antibiotic group (n = 89) were treated with local wound care and given either dicloxacillin, cephalexin, or erythromycin orally for seven days. Patients in the control group (n = 96) received local wound care only. All patients had their wounds irrigated with a 1% povidone-iodine solution and debrided and sutured if clinically indicated. All patients were subsequently reevaluated for clinical signs of wound infection. The groups were similar in age, sex, time of delay in seeking treatment, anatomic sites of wounds, depths and types of wounds, and number of wounds requiring suturing. The wound infection rates for the antibiotic and control groups were 1.1 and 5.1%, respectively. This difference was not significant (P = 0.212). There were 36 wounds in the antibiotic group and 37 wounds in the control group that were full thickness. The infection rates for these wounds were 2.8 and 13.5%, respectively. This was not statistically significant (P = 0.132). This study suggests that prophylactic oral antibiotics in low-risk dog bite wounds are not indicated. PMID- 1513729 TI - Uvulitis in three children: etiology and respiratory distress. AB - Uvulitis is an uncommonly reported disorder with the potential for significant morbidity. We describe three cases of uvulitis seen within a six month period in our emergency department. In two cases with respiratory distress, but without epiglottitis, Haemophilus influenzae was isolated from throat or blood cultures. The third case was associated with group A streptococcus tonsillitis and no respiratory compromise. Atypical presentations of upper airway infection with H. influenzae may be increasingly common. PMID- 1513730 TI - Pediatric streptococcal toxic shock syndrome. AB - Two children who presented with fever, rash, and hypotension were found to have group A beta hemolytic streptococcal toxic shock syndrome. These cases are reported to remind physicians who care for acutely ill children that exotoxin producing streptococci can produce clinical features and multisystem failure similar to staphylococcal toxic shock syndrome. PMID- 1513731 TI - A cystic gingival lesion associated with pneumococcal bacteremia. PMID- 1513732 TI - Scrotal involvement in Henoch-Schonlein purpura: a case report and review of the literature. PMID- 1513733 TI - Rooster attacks in childhood. PMID- 1513734 TI - Development of Kasabach-Merritt syndrome following needle aspiration of a hemangioma. AB - A case of Kasabach-Merritt syndrome that developed following needle aspiration in an infant with hemangioma is presented. Enlargement of the tumor leading to severe respiratory distress accompanied by hemorrhages occurred within six to eight hours after this simple intervention. The symptoms continued despite repeated thrombocyte transfusions and prednisolone therapy. Radiotherapy and local intraarterial corticosteroid therapy were attempted and led to some improvement. It took approximately three months for the platelet count and one year for the clinical state to revert to normal. This case illustrates that minor trauma may lead to life-threatening symptoms in a young infant with congenital hemangioma. PMID- 1513735 TI - Racial differences in childhood hospitalized pedestrian injuries. AB - This research provides an epidemiologic analysis of pedestrian-related injury discharges from The Children's Hospital of Alabama in Birmingham, utilizing a case-control design. Evidence is provided supporting the racial disproportionality of serious, nonfatal pedestrian injuries in children. These data indicate that pedestrian injuries resulting in hospitalization are more common among black children than among white children (odds ratio = 2.95) when compared with an age- and gender-matched control group of other hospitalized injuries. This racial association with pedestrian injury remained significant when the data were stratified by payment class, a proposed surrogate measure of socioeconomic status (adjusted odds ratio = 2.59). A catalog of harmful environmental factors that may be pervasive in black children's lives is provided as an aid in planning intervention programs and their evaluation. PMID- 1513736 TI - Legal concerns about the private patient in the pediatric emergency department. PMID- 1513737 TI - Stridor: a review. PMID- 1513738 TI - Physiologic monitoring systems, acute care. PMID- 1513739 TI - An aseptic meningitis picture from incipient brain abscess. AB - A preadolescent with headache and stiff neck presented for emergency department care. The presumptive diagnosis of viral meningitis was entertained on the basis of clinical examination and cerebrospinal fluid analysis. Events subsequent to his release from the department formed the stimulus for this report. It is apparent that patients with complicated sinusitis may present with a constellation of findings consistent with viral meningitis. PMID- 1513740 TI - Acute abdomen with right lower quadrant pain. PMID- 1513741 TI - A five year old with AIDS and dyspnea. PMID- 1513742 TI - Sickle cell disease and fever. PMID- 1513743 TI - Proposal for an administrative curriculum in pediatric emergency medicine fellowship training. AB - Administrative tasks make up a significant component of the practice of pediatric emergency medicine (PEM) physicians. Our survey of 10 academic pediatric emergency departments revealed that PEM physicians who are primarily clinical spent an average of 15% of their time on administrative tasks, and PEM physicians whose positions are administrative as well as clinical spent 30 to 60% of their time on administrative tasks. Of the 101 programs responding to our survey of 220 pediatric residency programs, 80% did not address hospital administrative issues, and many that did address these issues allowed these topics only one hour of presentation time per year. It is clear that there is a discrepancy between the demands placed upon PEM physicians to perform administrative tasks and the sparse or nonexistent opportunities for learning about administrative issues during residency training. It is incumbent upon pediatric emergency fellowship programs to provide an inclusive and well-structured administrative curriculum for their trainees. This article suggests a framework for such a curriculum. PMID- 1513744 TI - GBS bacteremia. PMID- 1513746 TI - Two-year-old boy with abdominal pain. PMID- 1513745 TI - Silver nitrate burns following treatment for umbilical granuloma. PMID- 1513747 TI - Neurotrophic factors: from physiology to pharmacology? AB - The recent cloning of new members of the nerve growth factor (NGF) family, namely brain-derived neurotrophic factor (BDNF) and neurotrophin-3 (NT-3), as well as the ciliary neurotrophic factor (CNTF) has greatly expanded our knowledge of the structural properties and neurotrophic activities of these proteins. Elucidation of their developmental and topographical expression and associated receptors in both the central nervous system (CNS) and peripheral nervous system (PNS) is proceeding at a brisk pace, leading us to propose a potential pharmacological use of these proteins. This possibility will ultimately rely upon a more complete understanding of the roles of these trophic factors in nervous system physiology and pathology. PMID- 1513748 TI - The pharmacology of the respiratory epithelium. AB - The airway epithelium is composed of a heterogenous population of cells and investigations on the epithelium have realized a number of important functions. With increasing use of cell isolation techniques, the function of individual cells within the epithelium is currently under investigation which will assist in the understanding of the role of airway epithelium in health. It is known that epithelial damage and/or impairment of epithelial cell function is a consistent feature of some respiratory conditions and whether such damage contributes to the disease is also under investigation. This review will summarize the current literature on the function(s) of the epithelium and its possible role in respiratory disease. PMID- 1513749 TI - The inhibitory effect of differently classified calcium antagonists on the calcium- and epinephrine-induced responses of isolated guinea-pig atria. AB - The effects of calcium antagonists diltiazem, flunarizine and N-(6-aminohexyl)-5 chloro-1-naphthalenesulfonamide (W7) were investigated on the calcium- and epinephrine-induced responses of guinea-pig spontaneously beating atria. All these calcium antagonists showed negative chronotropic and inotropic effects. Diltiazem (3 x 10(-8) M to 1.8 x 10(-7) M) antagonized both the action of epinephrine and calcium in a different manner but at the same concentrations. Flunarizine (1 x 10(-6) M to 1 x 10(-5) M) also antagonized both the action of epinephrine and calcium; but flunarizine weakly inhibits the calcium response at concentrations which have considerable antiadrenergic action. Only at the highest concentrations did both calcium antagonists show a decrease of the epinephrine maximum effect. W7 (1 x 10(-5) M to 1 x 10(-4) M) showed a mainly non-competitive antagonism against epinephrine but was practically ineffective against calcium. The results obtained suggest that a pharmacological prerequisite exists for classifying a calcium antagonist as a calcium entry blocker in the atrial muscle. Such a drug does not produce selective inhibition to calcium- and epinephrine induced responses. The ability or inability to inhibit the response to calcium represents the discriminant parameter for the action site of the calcium antagonist which are transmembranal fluxes or intracellular mechanisms respectively. PMID- 1513750 TI - Influence of profound hypothermia on the blood-brain barrier permeability during acute arterial hypertension. AB - In hypothermic rats with acute hypertension induced by intravenous injection of adrenalin, regional changes in blood-brain barrier permeability to macromolecules were investigated using Evans blue as indication. Evans blue albumin extravasation was determined as a macroscopic finding and a quantitative estimation with a spectrophotometer using homogenized brain to release the dye was also performed to evaluate the macroscopic findings. Five groups of rats were studied: Group I: normothermia + acute hypertension; Group II: hypothermia + acute hypertension; Group III: control hypothermia; Group IV: normothermia + hypotension; Group V: control normothermia. The rats were anaesthetized with diethyl-ether. Body temperature was lowered by submerging anaesthetized animals in an ice water bath. The colonic temperature was reduced to 20 +/- 1 degrees C. During adrenaline-induced acute hypertension the mean arterial blood pressure increased in both normothermic and hypothermic animals. Blood-brain barrier lesions were present in 40% of normothermic rats, and 60% of hypothermic rats after adrenaline-induced hypertension. Mean value for Evans blue dye in the whole brain was found to be 0.530 +/- 0.202 mg% in the normothermic rats and 0.752 +/- 0.256 mg% in the hypothermic rats during adrenaline-induced hypertension. This difference between normothermic and hypothermic rats was found to be statistically significant (P less than 0.01). Our results showed that the extravasation of Evans blue albumin was most pronounced in the brains of hypothermic rats compared to normothermic rats after adrenaline-induced acute hypertension. PMID- 1513751 TI - Epinephrine-induced pulmonary oedema in rats is inhibited by corticotropin releasing factor. AB - In various animal models of injury to skin, mucous membranes, muscle and brain, corticotropin-releasing factor (CRF) attenuated vascular leakage in the injured tissues. Here, the effects of CRF on a rat model of pulmonary oedema were examined. Male albino rats (220-290 g) received saline or CRF s.c., 30 min before pentobarbital anaesthesia, 60 mg/kg i.p., and 1 h before 1-epinephrine bitartrate (Epi), 30 micrograms/kg i.v. Within 30 min after Epi all (n = 27) saline pretreated rats were dead from pulmonary oedema, but animals receiving human/rat CRF at doses of 7 to 57 micrograms/kg s.c. (n = 25) were all alive. Body wt, wet and dry wt of lungs were used to calculate an oedema index. This index increased from 3.6 +/- 0.1 to 9.6 +/- 0.3 after Epi but was inhibited by 87% after CRF 28 micrograms/kg s.c. The ED50 of CRF for reducing pulmonary oedema was 3.2 (1.3 7.4) micrograms/kg s.c. Mean arterial pressure increased from 119 +/- 4 to 167 +/ 2 mmHg after Epi 10 micrograms/kg i.v., but was not different (118 +/- 3 to 169 +/- 4 mmHg) after CRF pretreatment, 6 micrograms/kg s.c., a dose which reduced lung oedema. Pharmacokinetic estimates suggest that plasma levels of CRF sufficient to attenuate lung oedema in rats approximate those seen in pregnant women at delivery, raising the possibility that endogenous CRF may protect the maternal organism during parturition. PMID- 1513752 TI - A heat released substance from rat ileal muscle. AB - Change in body temperature is reported to induce changes in muscle contraction by unconfirmed mechanisms. Therefore, the changes in isolated rat ileal muscle contractions at different surrounding temperatures were studied. The contraction was decreased by increase of the surrounding temperature from 37 degrees C to 40 degrees C, while it was increased by decrease of the temperature to 30 degrees C. Further, bathing the muscle in a conditioned medium prepared by incubation of the ileal muscle at 40 degrees C caused a decrease in contraction at a surrounding temperature of 37 degrees C. This indicates that increase of the temperature around muscles induces a release of the substance that causes a decrease in the contractile response. The effects of this heat-released substance were not blocked by propranolol, phentolamine and naloxone, or edrophonium, which indicates that these effects are not produced through an interaction with cholinesterase enzyme, alpha or beta adrenergic receptors or opiate receptors. PMID- 1513753 TI - Trisomy 5 mosaicism detected prenatally with an affected liveborn. AB - This paper reports a case of chromosomal mosaicism for trisomy 5 recovered from amniotic fluid cells and from skin fibroblasts of a liveborn dysmorphic male. Routine amniocentesis was performed at 16 weeks' gestation because of parental concern. Trisomy 5 cells were measured from 25 per cent of amniocytes from two culture vessels. No further invasive testing was performed until 32 weeks' gestation, at which time ultrasound examination showed a fetus with intrauterine growth retardation. Fetal blood sampling was then performed, with only karyotypically normal cells recovered. At birth, the child was found to have multiple dysmorphic features and congenital anomalies, including an eventration of the diaphragm and ventricular septal defect, both of which required surgical correction. Chromosomal analysis of cord blood lymphocytes indicated 46,XY; however, 20 per cent of the cultured fibroblasts obtained from the chest skin at the incision site for diaphragmatic repair had a 47,XY, +5 karyotype. Trisomy 5 mosaicism may be another example of tissue-limited mosaicism. Fetal blood sampling can then be falsely reassuring. Furthermore, because some cell lines rarely appear in lymphocyte populations, cytogenetic analysis of multiple tissues is warranted as part of the evaluation of individuals with developmental delay and dysmorphic features. PMID- 1513754 TI - In situ hybridization studies for the detection of common aneuploidies in CVS. AB - We have attempted to evaluate the efficiency of interphase cytogenetics in the detection of specific aneuploidies in chorionic villus samples. For this purpose, we used alphoid repetitive sequences specific for the chromosomes involved in the common aneuploidies, namely probes for chromosomes 13, 18, 21, X, and Y. These probes were applied to normal and abnormal CVS cases, as well as to a few mosaic cases. Results from these preliminary studies indicate that the technique can be very efficient for the detection of specific aneuploidies and can be particularly useful in the analysis of mosaic cases, which usually requires the screening of a high number of metaphases. PMID- 1513755 TI - A rare case of a false-negative finding in both direct and culture of a chorionic villus sample. AB - A discrepancy is reported between the karyotype of both direct and cultured chorionic villus cells (46,XX) and a fetal skin biopsy (47,XX, +18). The significance of this result is discussed and compared with similar discordant findings reported in the literature. PMID- 1513756 TI - A further prenatal diagnosis of mosaic tetrasomy 12p (Pallister-Killian syndrome) AB - A case of mosaic tetrasomy 12p was detected in amniotic fluid cell cultures from a 28-year-old woman referred to us at 26 weeks' gestation because of hydramnios. The fetus was shown on ultrasonography to have an omphalocele and a short femur length. Labour was induced at 32 weeks. An infant with multiple congenital anomalies was delivered and died after 10 min. The diagnosis of i(12p) or Pallister-Killian syndrome was confirmed cytogenetically in fibroblast and lymphocyte cultures. Increased LDH-B activity was demonstrated in fibroblasts. PMID- 1513757 TI - Prenatal sonographic diagnosis of diastematomyelia in a diabetic woman. AB - Diastematomyelia is a structural anomaly which concerns primarily the spine and secondarily the nervous structures contained in it. A case of early prenatal diagnosis (20th week) by ultrasound of diastematomyelia with associated diplomyelia in a diabetic woman is reported. Radiological and pathological examination of the fetus after therapeutic abortion confirmed the diagnosis. PMID- 1513758 TI - Ultrasonic diagnosis of mediastinal cystic hygroma. AB - The incidence of cystic hygroma, which represents dilated obstructed jugular lymph sacs, is 1 in 6000 pregnancies. Cystic hygromas can be located in the nuchal area or in any other location. The prenatal ultrasonic diagnosis of a cystic hygroma in the mediastinum is presented. PMID- 1513759 TI - Low maternal serum human chorionic gonadotrophin and unconjugated oestriol in a triploidy pregnancy. PMID- 1513760 TI - Non-invasive approach to prenatal diagnosis from maternal peripheral blood. PMID- 1513761 TI - Low fluorescence alpha satellite region yields negative result. PMID- 1513762 TI - Peculiar haematological features of fetuses with triploidy. PMID- 1513763 TI - Mosaic trisomy 15 found at amniocentesis. PMID- 1513764 TI - [Change of the complement level in patients with insulin-dependent diabetes mellitus in the course of intensified insulin therapy]. AB - Intensified insulin therapy in patients with type I diabetes mellitus is accompanied by a decrease in a total daily dose of insulin and the activity of the first 5 components of the classical pathway and CH50. A decrease in function of the first 5 components of the complement against a background of intensified insulin therapy can serve as a positive prognostic criterion of stabilization of development of diabetic angiopathies. PMID- 1513765 TI - [C-peptide and insulin ratio in patients with juvenile dyspituitarism in varying symptomatology]. AB - Altogether 24 adolescents with pubertal juvenile dyspituitarism (PJD) were investigated in the course of an oral GTT for 3 hours. The patients were divided into 3 groups: (1) with liver dysfunction and normal BP; (2) with normal liver and arterial hypertension; (3) with normal BP and normal liver function. The levels of glycemia, immunoreactive insulin, C-peptide and a molar C peptide/insulin ratio were measured. All the examinees were characterized by basal and stimulated hyperinsulinemia against a background of a normal C-peptide value, the absence of a tendency to IRI reduction by the end of the GTT. A decrease in the C-peptide/IRI ratio was marked in the 1st group. One of the reasons of hyperinsulinemia in PJD in parallel with high insulin secretory pancreatic function can be a decrease in the metabolic clearance of liver insulin, especially noticeable in patients with hepatocyte dysfunction. PMID- 1513766 TI - [Disorders of pulmonary hemodynamics in patients with diabetic nephroangiopathy and its correction with antioxidants]. AB - Hemodynamic changes of lesser circulation were investigated in 108 patients with diabetic nephroangiopathy. They were also given vitamin E therapy (8 micrograms/kg of body mass) for 2 weeks to correct metabolic derangements and indices of pulmonary hemodynamics. Partial renal function was determined with 131I-hippuran and 99mTc-DTPA renoscintigraphy. Pulmonary hemodynamics was assessed with pulmonary scintigraphy (MAA 99mTc). The results have shown that vascular renal lesions in diabetes mellitus cause hypertension of lesser circulation and disorders in pulmonary microcirculation, and disorders of lipid metabolism and activation of lipid peroxidation (LPO) progress with augmentation of severity of disease. Vitamin E therapy improves pulmonary hemodynamics, lipid metabolism and LPO. Antioxidant correction was most effective at the initial stages of diabetic nephroangiopathy. PMID- 1513767 TI - [Somatotropic function of the pituitary gland in patients with genetically determined forms of growth retardation]. AB - Altogether 144 patients with various forms of retardation of growth aged 1 to 24 were investigated. Somatotropic function of the pituitary body was assessed by the results of a stimulation test with clopheline. A STH level was determined by a radioimmunoassay. Somatotropic function was undisturbed in an overwhelming majority of cases of genetically determined retardation of growth. Hormone therapy was not indicated in these cases as it could lead to unfavorable results: decreased indices of definitive growth resulting from the formation of antibodies to the growth hormone. PMID- 1513768 TI - [Glucose tolerance disorders in patients with hypothyroidism]. AB - Altogether 42 patients with hypothyrosis of different etiology (aged 17 to 57) were investigated. According to the results of oral glucose tolerance test (OGTT) all the patients were divided into 3 groups: normal OGTT, disturbed OGTT and a flat type of glycemic curves. High levels of cortisol and free fatty acids (FFA) were detected in persons with disturbed OGTT. A lowered reaction to insulin was found in 15 patients with high levels of cortisol and FFA. Persons with unchanged sensitivity to insulin demonstrated a normal type of OGTT and normal blood levels of cortisol and FFA, and among patients with a low reaction to insulin there were persons with disturbed OGTT and high blood levels of cortisol and OGTT. Positive correlation was found between OGTT disturbances, on the one hand, and lowered sensitivity to insulin, increased blood levels of cortisol and FFA, on the other hand. A conclusion has been made that one of the causes of GTT disturbance in patients with hypothyrosis is an increase in the blood levels of cortisol and FFA and a decrease of sensitivity to insulin. PMID- 1513769 TI - [Surgical tactics in chronic autoimmune thyroiditis]. AB - Analysis of surgical treatment of 76 patients with Hashimoto's disease has shown that focal forms of disease are an absolute indication for operation: cancer was diagnosed in 6.6. per cent of patients in intraoperative verification. Progressive thyrotoxicosis or neck compression served as an indication in a diffuse form of lesion. PMID- 1513770 TI - [Status of the renin-angiotensin-aldosterone system in patients with a neuroendocrine-metabolic type of the hypothalamic syndrome]. AB - The paper is concerned with the results of a radioimmunoassay of the state of the renin-angiotensin-aldosterone system in patients with a neuroendocrine-metabolic type of the hypothalamic syndrome. They received pathogenetic therapy with peritol (an antiserotonin drug) or parlodel (a dopaminergic drug) during three months and routine therapy. The latter was not enough to return to normal the basal blood levels of aldosterone, reaction of the glomerular zone of the adrenocortical substance and the juxtaglomerular apparatus of the kidneys. Peritol therapy normalized the blood concentration of aldosterone; reactions of the glomerular zone of the adrenocortical substance and the juxtaglomerular apparatus to insulin hypoglycemia and furosemide acute testing improved considerably. After a course of parlodel therapy blood concentration of aldosterone got to normal, and reaction of the glomerular zone of the adrenocortical substance and the juxtaglomerular apparatus to insulin hypoglycemia was unchanged whereas it improved after furosemide testing. PMID- 1513771 TI - [A lethal outcome from neurogenic anorexia]. PMID- 1513772 TI - [Hyperandrogenic syndrome: problems of clinical terminology and symptomatology (lecture)]. PMID- 1513773 TI - [Algorithm for diagnosis and treatment of acromegaly]. PMID- 1513774 TI - [Oral therapy of patients with type II diabetes mellitus]. PMID- 1513775 TI - [Role of the liver in optimization of the thyroid status of rats in hypothyrosis caused by irradiation]. AB - Experiments were made on 100 random bred rats of various age groups, controls and animals exposed to single external gamma-radiation at a dose of 1 Gy on the 35th day of life. Thyroxine and triiodothyronine concentrations were investigated in peripheral blood and separately in arterial blood, in thyroid, portal and hepatic venous blood. The activity of T4 conversion into T3 by 5'-deiodinating enzymes of the liver microsomal fractions and the activity of the liver mitochondrial enzymes--cytochrome of C-oxidase and alpha-glycerophosphate dehydrogenase were also investigated. A decrease in thyroid excretion of T4 and T3 and T4 blood concentration was noted in rats exposed to irradiation. 5'-thyroxine deiodinating activity of the microsomal enzymes was elevated in the liver of such rats; a T3 ratio in the blood outflowing from the liver was on the increase. A conclusion has been made that 5'-deiodination in the liver of rats with postradiation hypothyrosis is effected as a result of increased production of the most active hormone T3 from less active T4. PMID- 1513776 TI - [Functional morphology of the thyroid gland in primary immunodeficiency]. AB - Morphological changes of the thyroid in non-inbred albino rats were analysed using a complex of histochemical methods. These data show the depression of functional activity against a background of primary immunodeficiency induced by neonatala thymectomy. PMID- 1513777 TI - [Influence of novodrin and obsidan on the secretory activity of tissue basophils of the thyroid and parathyroid glands]. AB - The task was to investigate secretory activity of sets of tissue basophils of the thyroid and parathyroids during administration of isoproterenol (novodrin) and propranolol (obsidan); 32 rats, divided into 2 groups, were given a single intraperitoneal injection of 20 mg of isoproterenol (the 1 st group) and 2.5. mg of propranolol (the 2nd group) with their subsequent decapitation with a 12 minute interval for 3 h. Six rats were controls. Increased tissue activity of tissue basophils was noted and interpreted as a result of elevated secretion of calcium regulating hormones developing under the influence of beta-adrenergic drugs. PMID- 1513778 TI - [Effect of prostaglandin E2 on ion regulating and acid excretory function of the kidneys]. AB - Prostaglandin E2 action on ion regulating and acid excretory function of the kidneys was investigated in acute experiments on intact male rats whose angiotensin-converting enzyme (ACE) had been blocked by enalapril. It was shown that i.p. two-fold PGE2 injection (0.5 mg/kg) during water load decreased diuresis, glomerular filtration, excretion of potassium, titration acids, ammonium, and increased urine pH. Sodium excretion was detected only if ACE had been blocked. In both series of experiments, an increase in chloride excretion was found to be statistically significant. A conclusion has been made that PGE2 influences directly the inhibition of acid excretory function of the kidneys. PMID- 1513779 TI - [Status of endemic goiter in the USSR]. PMID- 1513780 TI - [Probability of an association between HLA- and DR-antigens in nuclear families of patients with insulin-dependent diabetes mellitus]. AB - Insulin dependent diabetes mellitus (IDDM) is known to associate with various antigens and alleles of the HLA-system: DR3, DR4, and DQ-determinants. However penetration of the HLA-genes, predisposing to disease, is low, suggesting a possible role of additional genes outside the HLA-system in IDDM development. Among such genes there can be a group of heavy chain Ig genes (the Gm-system). The frequency of antigens of the Gm-system C1m(1) and C1m(2) and antigens of loci A, B, C and DR of the HLA-system was investigated in 92 Russians divided into 3 groups: 1 - IDDM patients from nuclear families (n = 35); 2 - their relatives of the 1st degree of kinship (n = 34); 3 - a random sampling (n = 23). The results obtained by A. A. Lopatenok and O. S. Budyakov (1973) were used as control data. No significant difference (p greater than 0.05) was found while comparing the frequency of Gm-phenotypes in IDDM patients from nuclear families with DR 4/X and in IDDM patients from nuclear families with another DR-phenotype, nor any significant difference was noted while comparing the frequency of Gm-phenotypes in IDDM patients from nuclear families and in patients from a random sampling with the HLA-phenotype DR 4/X. Thus the relationship of the Gm-system with IDDM through interrelationship with the HLA-DR-genes was undetectable. A conclusion was made that factors of the Gm-system played no significant role in predisposition to IDDM and could not be used as its genetic markers. PMID- 1513781 TI - [Dynamics of disorders of cellular and humoral immunity parameters in patients with insulin-dependent diabetes mellitus]. AB - Analysis of immunocompetent cell subsets in peripheral blood of patients with insulin dependent diabetes mellitus (IDDM) and the determination of sICA autoantibodies in their sera were performed by flow rate cytometry and compared to healthy donors and patients with noninsulin-dependent diabetes mellitus (NIDDM). It was shown that newly diagnosed IDDM was characterized by predominant disturbances of humoral immunity, and disease progression was mainly accompanied by cellular immunity disturbances. Exogenous insulin was one of the causes of such disturbances. A tendency to normalization of cellular rather than humoral immunity was observed after the onset of human monocompetent therapy of IDDM patients. It is likely that the appearance in the peripheral blood of activated T lymphocytes accompanied by sICA-autoantibodies and increased mature B-lymphocytes and NK-cells counts corresponds to increased ADCC against pancreatic beta cells in IDDM development. PMID- 1513782 TI - [Relationship between glucose utilization by tissues and residual insulin secretion and their role in the genesis of hyperglycemia in type I diabetes mellitus]. AB - Altogether 67 patients aged 16 to 50 suffering from insulin dependent diabetes mellitus (IDDM) of various duration were investigated to study the effect of peripheral sensitivity to insulin on genesis to hyperglycemia in type I diabetes mellitus. Residual beta-cell insulin secretory function was assessed by the level of C-peptide in a standard food test, and the rate of glucose utilization by tissues was studied by the clamp-method under the conditions of normoglycemia. The results obtained indicate the role of a decrease in peripheral sensitivity to insulin in genesis of hyperglycemia in diabetes mellitus, type I, and the presence of reciprocal interactions between glucose utilization and insulin secretion in IDDM patients and in controls. PMID- 1513783 TI - [Echostructure of the pancreas. Comparison with exocrine secretory activity of the pancreas in patients with diabetes mellitus]. AB - Qualitative disorders of an echopancreatogram are noted in half of patients with diabetes mellitus (both insulin dependent and noninsulin dependent). The most significant echopancreatographic quantitative and qualitative disorders were observed in diabetic patients with a maximal decrease in pancreatic enzyme excreting activity (on the basis of lipase and trypsin debit in a pancreozymin test, daily steatorrhea and chymotrypsin amount in daily feces). It has been assumed that a degree of ultrasound changes in the pancreas in diabetes depends on a degree of fibrosis of pancreatic exocrine tissue. Ultrasound investigations with quantitative and qualitative assessment of echopancreatograms is a valuable adjuvant diagnostic method in diabetes mellitus. PMID- 1513784 TI - [Dermatoglyphics in children with constitutional exogenous obesity]. AB - The results of investigation of dermatoglyphics were analyzed in 544 children suffering from constitutional exogenous adiposity. The results of population based studies of a regional medicogenetic counselling service (1240 persons) were taken as control data. Dermatoglyphic changes included papillary patterns intensified at the expense of loops and twists. An increase in the atd angle value, a-b count in boys, the presence of additional triradii, abnormal endings of the main palm lines, a reduced C line, the absence of the C triradius in patients with constitutional exogenous adiposity as well in their relatives of the 1st degree of kinship were revealed. PMID- 1513785 TI - [Clinical variants and symptomatic therapy of the climacteric syndrome]. AB - The paper is concerned with the results of therapy of the climacteric syndrome: the 1st group--typical CS with predominant emotional-vegetative dystonia of vagoinsular nature, skin sensitivity to a certain fraction of estrogens was increased, the 2nd group--CS complicated by hypertension, skin reaction to progesterone; the 3rd group--CS with emotional-vegetative dystonia of mixed type, skin sensitivity to estrogens and progesterone. Intracutaneous administrations of fractions of estrogens (E) and progesterone (P) were at a ratio of E:P = 4:1 for the 1st group, E:P = 1:1 for the 2nd and 3rd groups, causing a complete convalescence of 77 of 94 patients and a partial convalescence of 17 patients. In case of a partial therapeutic effect diet- and balneotherapy was recommended. PMID- 1513786 TI - [Impulse secretion of gonadotropins in patients with various forms of amenorrhea]. AB - Circahoral variations of gonadotropin secretion were investigated in 5 healthy women in the follicular phase of the menstrual cycle, in 8 patients with normogonadotropic amenorrhea, in 6 patients with hyperprolactinemic amenorrhea, in 4 patients with hypogonadotropic amenorrhea, and in 10 patients with amenorrhea associated with body mass deficiency. The levels of LH, FSH, prolactin, estradiol and progesterone were determined by radioimmunoassay every 20 min for 4 hours. The results suggest that the blood levels of gonadotropins in different types of amenorrhea are determined mainly by an amplitude of their impulses. PMID- 1513788 TI - [Syndrome of hyperandrogenism: principles of construction of a working classification (lecture)]. PMID- 1513787 TI - [A case of insuloma in a 14-year-old boy]. PMID- 1513789 TI - [Recommendations for control of diseases caused by iodine deficiency. Methods for assessment of iodine-deficiency states]. PMID- 1513790 TI - [Features of the formation, expression and transmission of basic genetic and androgen programs of the level of unusual estrogen-binding protein in sexually mature female rat hepatocytes under experimental conditions]. AB - Some features of the formation, expression and inheritance of basic genetic and androgen programs of the level of unusual estrogen-binding protein (UEBP) in mature female rat hepatocytes under experimental conditions were investigated. Liver regeneration after partial (2/3) hepatectomy of mature rats was used for generation of a new population of differentiated hepatocytes. The UEBP content was determined by radioligand technique in control liver and at 2, 4, 14 days of liver regeneration and related to the total DNA content as an indicator of cell proliferative activity. It was revealed that the basic genetic program of low UEBP level of hepatocytes of ovariectomized females was fully transferred to daughter cell during cell proliferation and characterized by a temporary elevation of its expression during initial steps of liver regeneration. It was shown that the androgen program of a high UEBP level was completely and stably formed after androgen action in hepatocytes of ovariectomized females and was fully transferred to daughter cells during hepatocyte proliferation. However experimentally formed androgen program of a high UEBP level in female hepatocytes was completely revealed only during early steps of liver regeneration (the 4th day), its expression was essentially declined after regeneration process was over. PMID- 1513791 TI - [Thyroid morphofunctional changes in various types of experimental chronic stress]. AB - Structural and functional parameters of the thyroid were studied in mature rabbits, inducing stress by stimulating the ventromedial nucleus of the hypothalamus or by exposing the animals to electrocutaneous irritations. Morphometric and radioimmunoassay results have revealed thyroid activation during the adaptation syndrome. Prolonged intensive stress was shown to cause a decrease in thyroid secretory activity, reflecting change of a stage of stable resistance by a phase of depletion of compensatory resources. However the nature of changes in the blood levels of thyroid and thyrotropic hormones in experimental animals have some characteristic features. A conclusion was made of the correlation between pathogenesis of the general adaptation syndrome and a methodological approach to simulation of a body tension reaction. PMID- 1513792 TI - [Effect of psychotropic drugs on the structure and function of the adrenal glands of control and stressed animals]. AB - The purpose of the experiment was to investigate the structure and function of the rat adrenal glands under chronic stress and its correction. Chronic stress is known to cause hypertrophy of the adrenals, enlargement of the area of nuclei and width of the cortical and medullary layers, a decrease in the content and pathological distribution of phospholipids, ascorbic acid and neutral lipids reflecting the function of these glands. Preventive courses of litonit, pikamilon and, to a lesser degree, piracetam and relanium weakened or removed characteristic pathomorphological changes in the adrenal structure. Complex analysis of the extracerebral mechanisms of each drug revealed the highest preventive activity of litonit which can be used to correct the adrenal glands under chronic stress. PMID- 1513794 TI - [A model of diabetes mellitus in dogs: combination of pancreas resection with intra-arterial administration of alloxan]. AB - A study was made of the indices of blood sugar on an empty stomach, GTT, blood insulin, body mass and the general status in 17 mongrels during one month after various types of resection of the pancreas: the 1st group--resection (80%), the 2nd group--resection (68%), the 3rd group--resection combined with intraarterial administration of alloxan. Insulin was determined using a standard kit RIO-INS-PG 125I by a radioimmunoassay. Alloxan was injected during operation at a dose of 250 mg (5% solution) in the upper pancreatoduodenal artery. Stable hyperglycemia, diabetogenic disturbances in GTT, a decrease in the blood level of insulin, and a clinical picture of diabetes mellitus were observed after operation in the 1st and 3rd groups. A new model of experimental diabetes mellitus in dogs (a combination of pancreas resection with intraarterial administration of alloxan) was recommended. PMID- 1513793 TI - [Liver nuclear phospholipids of rats with varying thyroid status]. AB - Thin-layer chromatography was used for fractionation of rat liver nuclear phospholipids after in vivo administration of 14C-sodium acetate. The administration of T3 to thyroidectomized rats caused a sharp increase in the incorporation of the label in all phospholipids of the nuclear fraction. The action of sphingomyelin and sphingomyelase on RNA-polymerase of nuclei isolated from the liver of thyroidectomized rats was tested. Sphingomyelin was shown to cause stimulation of RNA nuclear synthesis; parallel incubation with sphingomyelinase eliminated a stimulating effect of this phospholipid. PMID- 1513795 TI - [Neurons of cell populations of the solitary tract nuclei in rats of both sexes]. AB - The paper is concerned with the results of karyometric and light optic investigation of neurons of different neuron sets of nuclei of the solitary tract in mature rats of different sex. Neurons of 7 out 17 male subnuclei were shown to demonstrate structural features of higher functional activity as compared to similar female neuron sets. The correlation of functional morphology and a stage of the estrous cycle was observed in neurons of these subnuclei in female animals. Neurons of other subnuclei either did not change their activity during the estrous cycle or demonstrated signs of a decrease in function in the proestrous stage. PMID- 1513796 TI - [History of the study of diabetes mellitus]. PMID- 1513797 TI - [Formation and role of 5alpha-reduced androgens in man]. PMID- 1513798 TI - [Endemic goiter. Problems and solutions]. PMID- 1513799 TI - Familial pancreatic cancer: a family study. AB - The etiology of pancreatic cancer remains elusive. Recent attention has been given to host factors, as evidenced by the recognition of familial aggregations of this disease and its association with several hereditary cancer-prone disorders. We have investigated a remarkable family wherein pancreatic cancer has been documented through three generations, including progeny from two of the progenitor's three marriages. The protocol involved a search for documentation of cancer of all anatomic sites. We did not find any pattern of extrapancreatic cancer occurrences, and age at onset of pancreatic cancer corresponded to population expectations. The recognition of patients at high risk for pancreatic cancer should lead to research into potential environmental factors interacting with host susceptibility for elucidation of etiology and for earlier diagnosis. PMID- 1513800 TI - Treatment of duct carcinoma of the pancreas with the LH-RH analogue buserelin. AB - Thirty-six patients (21 male, 15 female) with ductal pancreatic cancer were treated with the long-acting synthetic luteinizing hormone releasing hormone (LH RH) analogue buserelin. All patients had advanced tumor stages (stage II: 7 patients; stage III: 11 patients; stage IV: 18 patients). A monthly follow-up including clinical status, computed tomography scan, or ultrasonography and the tumor markers carcinoembryonic antigen (CEA) and H carbohydrate antigen 19-9 (CA19-9) was carried out. There were no severe side effects apart from impotency in men and hot flashes and outbreaks of perspiration in three patients. No partial or complete remission was seen. Twenty-six patients showed tumor progression with a median survival time of 4 months (range 0.5-11 months). In 10 patients a "no change" evaluation with a median survival time of 10 months (range 8-17 months) was registered. In only two of these patients there was no increase in the serum tumor markers CA19-9 and CEA during this time. In conclusion, LH-RH analogue treatment cannot be recommended in this selected group of patients suffering from advanced tumor stages of pancreatic cancer. PMID- 1513801 TI - Effect of taurocholate on CCK release and pancreatic secretion produced by two CCK-releasing peptides in conscious rats. AB - The role of luminal bile salts (taurocholate) in regulation of rat pancreatic secretion was examined by studies on the effects of luminal stimulants on the pancreas during infusion of various concentrations of taurocholate into the duodenum of conscious rats. Rats with external bile and pancreatic fistulae were used. For 24 h before the experiment, pancreatic juice was excluded from the intestine but bile was continuously returned to the duodenum. From the beginning of the experiment, 8-200 mM of taurocholate was infused at a rate of 1 ml/h instead of returning the bile. Pancreatic juice was collected for a 2-h period and then 2 micrograms of pancreatic secretory trypsin inhibitor-61 (PSTI-61) (= monitor peptide) or partially purified putative CCK-releasing peptide from rat intestine (intestinal CCK-RP) was injected into the duodenum (1 ml/min). Continuous infusion of taurocholate maintained a constant rate of pancreatic secretion, except at a concentration of 8 mM, which resulted in a slight increase in pancreatic secretion. Both PSTI-61 and intestinal CCK-RP significantly increased pancreatic secretions during infusion of 20 or 40 mM taurocholate, but had no significant effect during infusion of 80 or 200 mM taurocholate. Therefore, higher concentrations of taurocholate in the intestine prevented the stimulatory effects of luminal stimulants, probably by preventing the latter from reaching CCK cells. PMID- 1513802 TI - The effect of pituitary adenylate cyclase activating polypeptide (PACAP) on exocrine pancreatic secretion in dogs. AB - The effect of new hypothalamic peptides, PACAP38 and PACAP27, on exocrine pancreatic secretion was studied in five conscious dogs each with a chronic gastric fistula and a Thomas duodenal fistula. The intravenous injections of PACAP38 and PACAP27 (2.5-100 pmol/kg) induced dose-related increases in pancreatic fluid, bicarbonate, and protein secretion. The potency of PACAP27 was equal to that of VIP but was only 1/100 that of secretin; PACAP38 was less active (less than 1/10) than PACAP27. PACAP38 and PACAP27, in contrast to secretin and VIP, stimulated protein secretion; the potency of the former was about 1/10 that of the latter. The peak response to PACAP27 was about 44% of the maximal response to CCK8. Pancreatic protein secretion, but not fluid and bicarbonate secretion, in response to PACAP38 and PACAP27 was significantly (p less than 0.05) reduced by atropine. It is concluded that PACAP has a VIP-like action on pancreatic fluid and bicarbonate secretion in conscious dogs, but differs from VIP in stimulating protein secretion via a cholinergic mechanism. PMID- 1513803 TI - Experimental hybrid islet transplantation: application of polyvinyl alcohol membrane for entrapment of islets. AB - In this study, we first examined in vitro a polyvinyl alcohol membrane to be used to contain hybrid islet cells, and second we tested a bioartificial pancreas with entrapment of pancreatic islets in polyvinyl alcohol membrane in rats with experimentally induced diabetes. The permeability of the polyvinyl alcohol membrane to different substances was studied in a two-cell chamber system. Glucose, insulin, and nutrients passed through the membrane easily, whereas the passage of immunoglobulin G was completely prevented, indicating that this membrane could be effective in protecting the bioartificial pancreas from immunorejection. Approximately 2,000 islets collected from three Sprague-Dawley rats were enclosed in a mesh-reinforced polyvinyl alcohol tube and transplanted into the peritoneal cavity of six Wistar rats with streptozotocin-induced diabetes. Their nonfasting serum glucose levels were significantly decreased for at least 12 days. Six diabetic rats receiving intraperitoneal transplantation of free islets without the tube showed a slight but significant decrease in nonfasting serum glucose levels for only 3 days. One diabetic rat with transplantation of the bioartificial pancreas had a significant and sustained decrease in nonfasting glucose levels from pretransplanted levels of 440-500 mg/dl to a mean value of 162 +/- 13 mg/dl for over 3 months without immunosuppression. The bioartificial pancreas was then removed, and glucose levels gradually increased to over 500 mg/dl. The results of the present study suggest that a bioartificial pancreas with entrapment of islets in a polyvinyl alcohol membrane could be a promising therapeutic approach to diabetes mellitus. PMID- 1513804 TI - Development of diabetic complications in a new diabetic strain of rat (WBN/Kob). AB - The development of ocular, renal, and neural lesions was examined in male diabetic WBN/Kob rats with endoexocrine pancreatic insufficiency. As for the ocular lesions, around 15 months of age, opacity of the lens began to appear. Opacity was first observed in the periphery of the lens, and then increased rapidly in severity, extending concentrically and centripetally, until total cataracts developed. The incidence of cataracts in male rats was gradually increased and reached almost 100% at 24 months of age. As for renal lesions, the 24-h urinary total protein began to increase at about 13 months of age and reached 50-300 mg/24 h at 13-28 month of age, which was significantly higher than in age-matched male Wistar rats (15-25 mg/24 h). Electrophoretic analysis revealed that the urinary protein was almost all albumin. Morphologically, an increased GBM thickness and glomeruli with segmental or global enlargement of mesangial areas were observed. As for neural lesions, a reduction in motor nerve conduction velocity was demonstrated electrophysiologically, and a marked decrease in density and diameter of myelinated fibers in the sciatic nerves were observed morphometrically. In conclusion, the WBN/Kob rat strain with slowly developing but severe lesions associated with pancreatopathy presents a suitable model for human diabetic complications. PMID- 1513805 TI - Diabetes manifestation in BB rats is preceded by pan-pancreatic presence of activated inflammatory macrophages. AB - Pancreata of normoglycemic diabetes-prone (dp) and diabetes-resistant (dr) BB rats and normal Wistar rats were screened for macrophage infiltration by immunohistochemistry and by electron microscopy. Inflammatory macrophages were found in the endocrine as well as the exocrine part of the pancreata from dp BB rats. In the exocrine tissue they had a different phenotype (ED1+, ED2+, W3/25+, Ox17+) from that found in pancreata from dr BB and Wistar rats (predominantly ED1 , ED2+, W3/25+, Ox17-). The number of macrophages in exocrine portions of pancreata from the various rat strains were not different. By electron microscopy scattered macrophage-associated tissue lesions and phagocytosis of cell debris were found throughout the exocrine tissue and in islets of dp BB rats. Such lesions were low or absent in biopsies of animals that later did not develop diabetes. We conclude that macrophage-mediated cytotoxicity during the early phases of diabetes development in BB rats is not restricted to islets, but is a generalized, pan-pancreatic event. PMID- 1513806 TI - Responsiveness and memory of the pancreatic B-cells to the insulin secretagogues D-glucose and L-arginine in prediabetic and diabetic rabbits. AB - Non-insulin-dependent diabetes was obtained in rabbits following pancreatic duct ligation. The insulin responses to D-glucose and to L-arginine were studied in the isolated perfused pancreas of control, prediabetic, and diabetic rabbits. In controls, D-glucose or L-arginine caused biphasic insulin release that was qualitatively and quantitatively altered in both prediabetic and diabetic animals. Most secretagogues influence the islet response to other secretagogues by modifying the B-cell memory. In perfused control pancreas, the priming effect of D-glucose resulted in a time-dependent potentiation (TDP) of insulin release during subsequent L-arginine stimulus, whereas L-arginine induced a time dependent inhibition (TDI) of insulin release during subsequent D-glucose stimulus. As compared with the controls, the TDP effect obtained was emphasized in prediabetic and strongly diminished in diabetic animals. In some prediabetic and diabetic cases, the TDI remained unchanged compared with the controls, and in others it diminished in prediabetic and disappeared in diabetic animals where the effect became one of TDP. The effects of TDP and TDI seem to evolve independently of the modifications of the responsiveness to B-cell secretagogues. PMID- 1513807 TI - Evidence for a direct inhibitory effect of PYY on insulin secretion in rats. AB - Peptide YY (PYY) has been shown to inhibit stimulated insulin secretion under in vivo conditions in the mouse, the rat, and the dog. In the present study, we investigated the effects of PYY on insulin secretion from the isolated perfused rat pancreas and isolated rat islets. In isolated pancreas perfused in presence of 8.3 mM glucose, PYY at 10(-10) and 10(-9) M, but not at 10(-8) M, inhibited insulin secretion. In the presence of 5.5 mM glucose, PYY (10(-9) M) did not modify basal insulin release but reduced the biphasic insulin response to arginine (10 mM). PYY also markedly reduced the pancreatic vascular flow rate; this effect was observed at all three concentrations tested in a dose-dependent manner. In isolated islets, glucose (15 mM)-stimulated insulin secretion was inhibited by PYY at 10(-7) M. We conclude that in the perfused rat pancreas, PYY inhibits insulin secretion and induces vasoconstriction without a causal relationship. In addition, our results on isolated islets suggest that the inhibitory action of PYY on insulin secretion is exerted through a direct islet action. PMID- 1513808 TI - Adenocarcinoma of the pancreas with osteoclast-like giant cells: a case report with immunocytochemistry. AB - Histological examination of a tumor centered in the body of the pancreas of a 65 year-old Iranian man revealed it to have a substantial component in which osteoclast-like giant cells were set within a stroma of pleomorphic mononuclear cells though other areas were composed of conventional adenocarcinoma. Immunocytochemistry was used to investigate the differentiation of the various component cells of the tumor. The carcinoma cells of the usual type expressed epithelial antigens (EMA and cytokeratin). The giant cells expressed vimentin and showed membrane staining with anti-LCA, in common with examples of cells originating from the mononuclear phagocytic system, including normal osteoclasts. The accompanying stromal cells expressed vimentin only. This implies that the giant cells are likely to have their origin in the bone marrow, whereas the mononuclear stromal cells that separate them may represent tumor cells that have lost their epithelial phenotype. The giant cells are therefore an unusual tissue response to the presence of the carcinoma. PMID- 1513809 TI - CA 19-9 and diagnosis of pancreatic carcinoma. PMID- 1513810 TI - [An evaluation of the index of the satisfaction with care. The questionnaire on quality of care in medicine]. PMID- 1513811 TI - [Experience in evaluating the quality of nursing care with the questionnaire method]. PMID- 1513812 TI - [Notwithstanding]. PMID- 1513813 TI - [The professional identity of the nurse in relation to the reorganization of models of care in hospital bed units]. PMID- 1513814 TI - [The importance of feeding in regulating intestinal functions in the stoma patient]. PMID- 1513815 TI - [In what direction are the latest legislative proposals leading the nursing profession?]. PMID- 1513816 TI - Incest: the family context. Understanding and detecting childhood sexual abuse. AB - The recorded incidence of child abuse is higher than many nurses might imagine, and adult incest survivors often suffer long-term psychological effects. An awareness of the characteristics marking families where abuse takes place can alert nurses to such cases--both past and present. PMID- 1513817 TI - Non-invasive assessment of phrenic nerve function in infants following cardiac surgery. AB - PND occurs more frequently following cardiac surgery than was previously thought. Electrophysiological phrenic nerve testing is a reliable early test of the nerve's function. Phrenic nerve damage, particularly in children under 18 months of age, increases the risk of respiratory morbidity. Early diagnosis enables appropriate planning and treatment. PMID- 1513818 TI - Promoting the motivation to change. The role of facilitative leadership in quality assurance. AB - Quality assurance initiatives depend on the motivation of committed clinically based staff to succeed. A bottom-up approach encourages staff to identify priorities and goals in the knowledge that significant and valid changes can be made. PMID- 1513819 TI - A team to ensure sensitive continuing care. Setting up a symptom control/support team. AB - The stress and responsibility associated with palliative care is demanding for patients and healthcare professionals. A symptom control/support team can act as a resource for all involved, offering advice on symptom control, counselling, education and bereavement follow-up. PMID- 1513820 TI - First step towards a desired outcome. Preventing infection by risk recognition. AB - The need for effective infection control applies to all areas of patient care, but is often carried out on an ad hoc basis. Implementing infection control procedures as part of the nursing process will ensure this area of care is not overlooked. PMID- 1513821 TI - An appetite for life. Assessing and meeting nutritional needs. AB - Admitting patients to hospital provides nurses with an excellent opportunity to assess nutritional needs and intake. It also presents them with a challenge to ensure patients accept the meals offered to them. Establishing an acceptable mealtime routine and helping patients to make menu choices can help them achieve this. PMID- 1513822 TI - Objective assessment ensures improved diagnosis. Principles and techniques of urodynamics. AB - Nurses are playing an increasingly active role in urodynamic investigations, and need to understand the principles and techniques involved. This article offers an overview of the diagnostic function urodynamics play in urinary incontinence. PMID- 1513823 TI - The ebb and flow of heart disease. Circadian rhythms and coronary heart disease. AB - Circadian rhythms have been shown to influence morbidity and mortality associated with heart disease, and most heart attacks occur in the early morning. An awareness of this link can motivate clients to comply with 24-hour medication. PMID- 1513824 TI - Respiratory measurements. 2: Interpreting simple measurements of lung function. AB - 1. When lung function is being measured, it is important that it is accurately interpreted and reported. 2. Clinical history and previously recorded values should be taken into account. 3. When correctly interpreted, measurements can provide useful information to aid diagnosis. PMID- 1513825 TI - Information will enhance compliance. Informing clients about compression hosiery. AB - Clients are more likely to wear compression hosiery and look after it properly if they understand how it works. Community nurses can enhance their clients' compliance by educating them about the role compression hosiery plays in treating and preventing venous disease. PMID- 1513826 TI - An alliance when you need it. PMID- 1513827 TI - PREP is vital to ensure a baseline of skills. PMID- 1513828 TI - Extending the parental role. Involving parents in paediatric care. AB - Most children admitted to hospital would prefer to be cared for by their parents. Care by parent units enable parents to fulfil this role with the encouragement and support of paediatric nurses. PMID- 1513829 TI - Emotional support can precipitate recovery. Setting up a counselling service for breast cancer patients. AB - Many women who are diagnosed with breast cancer do not receive the counselling and support they require. Nurse counsellors are well-equipped to take on this responsibility, and can help women consider their treatment options. PMID- 1513830 TI - Understanding motor neurone disease. AB - Understanding of neurological disorders has improved in recent years, enhancing nursing involvement in this area of care The nurses' role as the key worker within a multidisciplinary team identifies their management skills. Nursing care of people with motor neurone disease centres upon PMID- 1513831 TI - Writing for publication: part of your career development. AB - Nurses are increasingly being motivated to write for publication, and indeed this now plays an important part in career development. An understanding of the publishing procedure and an awareness of the need for a simple, clear writing style will equip nurses to take on this new and challenging role. PMID- 1513832 TI - Attrition, attrition--we all fall down. Re-evaluating staff selection and retention. AB - Students who drop out of pre-registration nurse education not only represent a lost opportunity, but also a waste of time, effort and precious resources. The changes heralded by Project 2000 make this an ideal time to re-evaluate attitudes towards recruitment. PMID- 1513833 TI - A moist, odour-free environment. A multicentred trial of a foamed gel and a hydrocolloid dressing. AB - Exuding wounds such as leg ulcers present special problems. A clinical trial of a new foamed gel dressing showed that it provides a moist healing environment without unacceptable odour, and improves the condition of the wound when compared to a hydrocolloid dressing. PMID- 1513834 TI - Glasgow Coma Scale. PMID- 1513835 TI - Establishing the cost of comfort. Effectiveness of mattresses in pressure sore prevention. AB - The treatment of pressure sores exerts a significant drain on NHS resources. Identifying mattresses which help to prevent pressure sores can result in substantial long-term savings. PMID- 1513836 TI - Creating educational opportunities to improve care. Management of the oedematous limb. AB - Lymphoedema was until recently accepted as a distressing condition which was difficult to manage. The development of new treatment strategies means this condition can now be controlled. Effective education initiatives are essential to ensure that these developments are widely implemented. PMID- 1513837 TI - In touch with the world outside. Managing sensory changes in elderly people. AB - The inevitable deterioration of the senses associated with ageing can significantly affect older people's quality of life. Adapting daily routines and the home environment to cope with these changes can restore temporarily lost independence. PMID- 1513838 TI - A hospice for Leningrad. PMID- 1513839 TI - Reward summation and the effects of pimozide, clonidine, and amphetamine on fixed interval responding for brain stimulation. AB - Two models of reward summation were examined in 16 rats lever pressing for intracranial stimulation under fixed-interval (FI) reinforcement. The first model examined rate-frequency functions and the second model traded off frequency and train duration. The second model was selected to assess the effects of three drugs on reward summation. Both clonidine and pimozide inhibited FI self stimulation, but pimozide's effect could not be distinguished from a performance deficit. Two amphetamine isomers facilitated self-stimulation in a manner suggesting enhanced reinforcement. The dextro isomer was four times more effective than the levo isomer to facilitate self-stimulation. This study shows that the combination of the FI schedule with a reward-summation model is well suited for evaluating the effects of drugs on self-stimulation. The advantages of this model are that inter-reinforcement intervals are separated, which minimizes priming and stimulation aftereffects, and more responding does not increase stimulation availability, thus eliminating rate-dependency effects. PMID- 1513840 TI - Antagonism of U-50,488H-induced antinociception by ginseng total saponins is dependent on serotonergic mechanisms. AB - Morphine-induced antinociception was prevented by pretreatment with ginseng total saponins in the tail-pinch and tail-flick tests carried out in mice. The antinociceptive effect of U-50,488H, a selective kappa-opioid receptor agonist, was prevented by naloxone, a nonselective opioid receptor antagonist, in the tail pinch but not in the tail-flick test. However, U-50,488H-induced antinociception was prevented by ginseng total saponins in the tail-flick but not in the tail pinch test. These results indicate that nonopioid mechanisms are involved in the antagonism of U-50,488H-induced antinociception by ginseng total saponins. In addition, the antagonism of U-50,488H-induced antinociception in mice pretreated with ginseng total saponins was abolished by pretreatment with a serotonin precursor, 5-hydroxytryptophan, but not by a noradrenaline precursor, L dihydroxyphenylalanine, in the tail-flick test. Therefore, it appears that the antagonism of U-50,488H-induced antinociception by ginseng total saponins is dependent on serotonergic mechanisms. PMID- 1513841 TI - Effects of Ginkgo biloba extract (EGb 761) on the guinea pig vestibular system. AB - Previous studies have demonstrated that the administration of Ginkgo biloba extract (EGb 761) improves the compensation of the vestibular syndrome induced by transection of the VIIIth nerve. To investigate the mechanisms at play, the vestibular nuclei of alert guinea pigs were perfused with EGb 761. This perfusion always induced a stereotyped reversible postural syndrome that was the mirror image of the syndrome provoked by the unilateral lesion of the otolithical receptors. This result supports the hypothesis that EGb 761 has a direct excitatory effect on the lateral vestibular nuclei (LVN) neurons. In a second step, we quantified the horizontal vestibuloocular reflex (HVOR) of the normal guinea pig following IP injection of EGb 761. In normal guinea pig, IP administration of EGb 761 led to a reversible, dose-dependent decrease of the HVOR gain without affecting the phase of the reflex. These data help to explain the therapeutic effects of EGb 761 during vestibular syndromes and strongly suggest an impact at the neuronal level. PMID- 1513842 TI - Interaction of pregnanolone and pregnenolone sulfate with ethanol and pentobarbital. AB - 3-alpha-Hydroxy-5-beta-pregnan-20-one [pregnanolone (PA)] and 3-beta-hydroxy-5 pregnen-20-one 3-sulfate [pregnenolone sulfate (PS)] are steroids that have been shown in biochemical studies to be active at the GABA-benzodiazepine-chloride receptor complex, Pa as a "barbiturate-like" agonist and PS as a "picrotoxin like" antagonist. Since other compounds that are active at this site interact with the effects of pentobarbital and ethanol, the behavioral effects of these steroids alone and in combination with pentobarbital and ethanol were tested. Pa blocks the convulsions caused by pentylenetetrazole (PTZ) and increases motor activity when given alone in low doses. In combination with either pentobarbital or ethanol, it enhances the depression in motor activity, hypothermia, and hypnosis. In contrast, PS has no effect on PTZ convulsions and depresses motor activity by itself. With pentobarbital, PS enhances the depression in motor activity but has no effect on hypothermia or hypnosis. With ethanol, PS enhances the hypothermia but does not affect motor activity or hypnosis. Therefore, Pa and PS show different but not opposite effects in interacting with compounds active at the GABA-benzodiazepine-chloride receptor complex. PMID- 1513843 TI - Potentiation of the dorsal immobility response following intrastriatal injections of enkephalins. AB - The effects of bilateral intrastriatal injections (1.0 microgram/side) of leucine5- and methionine5-enkephalins and their related nonopiate fragments upon three measures of immobility over a time course were investigated. Both leucine5 enkephalin and des-Tyr1-leucine-enkephalin potentiated the duration of the dorsal immobility response (DIR) 15 min postinjection and over a 1-h time course. On the other hand, methionine5-enkephalin and des-Tyr1-methionine-enkephalin potentiated the duration of the DIR at 5 and 15 min. These enkephalins and their fragments had no effect upon vertical cling and bar catalepsy. In a second study, an SC injection of 4 mg/kg naloxone 15 min prior to the central injections blocked the potentiation of the DIR effects of the enkephalins. PMID- 1513844 TI - Direct microinjection of cathinone into the rat brain produces discriminative stimuli. AB - Rats were trained to discriminate IP administration of 800 micrograms/kg cathinone using a food-motivated, two-lever discrimination procedure. Following training, 800 micrograms/kg cathinone discrimination was produced (generalized) by lower cathinone doses in a dose-responsive manner after IP administration; an ED50 value of 330 micrograms/kg was calculated. Subsequently, guide cannulae were implanted into the lateral ventricle and bilaterally into the nucleus accumbens. After recovery, injections were made via cannulae that extended 0.5 mm past the tip of the guide cannulae. ICV administration of 256 micrograms cathinone/rat produced discriminative responding on the cathinone-appropriate lever to the same degree as did the peripherally administered training dose of cathinone. Decreasing ICV doses produced decreased discriminative performance and allowed the calculation of an ED50 value of 90.5 micrograms. Likewise, administration of 64 micrograms cathinone/nucleus accumbens (for a total of 128 micrograms/rat) substituted for the IP training dose of cathinone. These results evidence the central mediation of the cathinone-induced discriminative stimulus cue and show that administration of cathinone into the nucleus accumbens is sufficient to produce these stimuli. Thus, these data suggest that receptors in the nucleus accumbens are important for the discrimination of this psychostimulant. PMID- 1513845 TI - Phencyclidine does not disrupt latent inhibition in rats: implications for animal models of schizophrenia. AB - Latent inhibition (LI) is a behavioral paradigm in which prior exposure to a stimulus not followed by reinforcement retards subsequent conditioning to that stimulus when it is paired with reinforcement. The development of LI reflects a process of learning to ignore, or tune out, irrelevant stimuli. Three experiments investigated the effects of phencyclidine (PCP) on LI. The investigation was carried out using a conditioned emotional response (CER) procedure consisting of three stages: preexposure, in which the to-be-conditioned stimulus, tone, was repeatedly presented without reinforcement; conditioning, in which the preexposed stimulus was paired with shock; and test, where LI was indexed by animals' suppression of licking during tone presentation. The three stages were conducted 24 h apart. In Experiment 1, 1 mg/kg PCP was administered either in the preexposure or in the conditioning stage or in both. Experiment 2 used 5 mg/kg PCP in the same procedure. In Experiment 3, 5 mg/kg PCP was administered throughout the LI procedure, including the test stage. In all three experiments, PCP did not affect LI. The implications of these findings for the development of animal models of schizophrenia are discussed. PMID- 1513846 TI - Oral caffeine consumption by rats: the role of flavor history, concentration, concurrent food, and an adenosine agonist. AB - Some determinants of caffeine consumption by rats were examined using the two bottle choice test. To describe the role of flavor history, groups of eight rats each received one of three fluids as their only source of fluid beginning at 29 days of age and continuing throughout the experiments. One group ("water") received tapwater, a second group ("caffeine") received 0.5 mg/ml caffeine in tapwater, and a third group ("quinine") received 0.01 mg/ml quinine in tapwater. Two-bottle choice tests began when rats were 40 days old. In the initial tests, caffeine rats drank more caffeinated water than water rats. Quinine rats were midway between these two groups. On a second block of tests, quinine and water rats' caffeine consumption increased so that the three groups were indistinguishable. When 0.5 mg/ml caffeine was available for 24 h, about one third of the total fluid consumption was of caffeinated water for all three groups. The presence of food greatly increased both caffeine and water consumption across a range of caffeine concentrations spanning 0.125-4.0 mg/ml. Increasing caffeine concentration generally increased consumption of plain water and decreased that of caffeinated water (but not total caffeine consumed) for water rats. Caffeine rats generally drank more caffeine than water rats, largely due to a tendency toward increased consumption of the 0.5-mg/ml concentration. Consumption of caffeinated water peaked at 0.5 mg/ml and showed graded decreases at higher and lower concentrations. Caffeine consumption showed dose-related increases with presession administration of l-phenylisopropyl adenosine. The serines of experiments characterize some of the determinants of caffeine consumption in rats.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1513847 TI - Naltrexone, serotonin receptor subtype antagonists, and glucoprivic intake: 1. 2 Deoxy-D-glucose. AB - Inhibition of deprivation-induced intake by naloxone was significantly enhanced by the 5-hydroxytryptamine3 (5-HT3) antagonist ICS-205,930. Interactions between naloxone and either the general 5-HT antagonist methysergide or the 5-HT2 antagonist ritanserin or ketanserin produced smaller effects. The present study evaluated whether 2-deoxy-D-glucose (2DG, 400 mg/kg) hyperphagia was affected by methysergide (0.5-5 mg/kg), ritanserin (0.25-2.5 mg/kg), or ICS-205,930 (0.5-5 mg/kg) alone or in combination with naltrexone (0.25 and 2.5 mg/kg). Only ICS 205,930 stimulated spontaneous intake for up to 4 h in the light cycle. Only ritanserin (1.25 mg/kg) transiently reduced 2DG hyperphagia. The dose-dependent decreases in 2DG hyperphagia by naltrexone were significantly enhanced by the dose range of ICS-205,930. The inhibition of 2DG hyperphagia by the low naltrexone dose was enhanced by methysergide (5 mg/kg) and ritanserin (1.25 mg/kg). These data suggest that the 5-HT3 receptor primarily interacts with opioid systems to modulate 2DG hyperphagia and that one possible locus of interaction is in the caudal brainstem. PMID- 1513848 TI - Naltrexone, serotonin receptor subtype antagonists, and glucoprivic intake: 2. Insulin. AB - Opiate antagonist inhibition of deprivation-induced intake and 2-deoxy-D-glucose (2DG) hyperphagia is significantly enhanced by the 5-hydroxytryptamine3 (5-HT3) antagonist, ICS-205,930. Interactions between opiate antagonists and either 5-HT or 5-HT2 antagonists produced smaller effects. The present study evaluated whether insulin (5 U/kg) hyperphagia was affected by methysergide (0.5-5 mg/kg), ritanserin (0.25-2.5 mg/kg), and ICS-205,930 (0.5-5 mg/kg) alone or in combination with naltrexone (2.5-10 mg/kg). Whereas ICS-205,930 stimulated insulin hyperphagia across the 6-h time course, ritanserin and, to a lesser degree, methysergide reduced insulin hyperphagia. Naltrexone marginally (19-33%) reduced insulin hyperphagia. Pairing naltrexone with either ICS-205,930 or ritanserin significantly suppressed insulin hyperphagia after 2 h. Pairing naltrexone with each of the serotonin antagonists significantly enhanced insulin hyperphagia after 4 and 6 h. These data suggest that 5-HT2 and 5-HT3 receptor subtypes interact with opioid systems to modulate insulin hyperphagia. Given that central insulin reduces food intake and body weight, the interaction between serotonergic and opioid systems may occur peripherally. PMID- 1513849 TI - Reduction of flurazepam's antiseizure efficacy persists after stress. AB - Twenty-four hours after mice were forced to swim for up to 10 min in cold (6 degrees C) water, the ability of flurazepam to antagonize the electrical precipitation of seizures was reduced. This stress-induced reduction in flurazepam's antiseizure efficacy persisted for at least 72 h; but was absent 1 week after the single session of swim stress. The data may be relevant to stress related psychiatric disorders and suggest that the therapeutic efficacy of benzodiazepines may be altered after a severe stress. PMID- 1513850 TI - A-71623, a selective CCK-A receptor agonist, suppresses food intake in the mouse, dog, and monkey. AB - The anorectic actions of cholecystokinin (CCK)-8 and of a selective CCK-A agonist, A-71623, were examined in CD1 mice, beagle dogs, and cynomolgus monkeys. A-71623 suppressed intakes in all species tested, and the effects were blocked by a selective CCK-A antagonist, A-70104. In the dog only, CCK-8 was more potent on a molar basis compared to A-71623, although the effects of both CCK agonists were more short-lived in the dog compared to the other species tested. Our results support other evidence suggesting that the anorectic actions of exogenous application of CCK-8 in these species are mediated via stimulation of the CCK-A receptor subtype. PMID- 1513851 TI - Effects of d-amphetamine on the recovery of function following cerebral ischemic injury. AB - Amphetamine with appropriate motor experience has been found to facilitate the recovery of motor function after several different types of brain injuries. We investigated whether amphetamine would hasten the recovery of spatial mapping ability in gerbils previously subjected to a 3-min episode of forebrain ischemia. Amphetamine did not promote behavioral recovery, nor did it attenuate ischemic cell damage of hippocampal CA1 neurons. The beneficial effects of amphetamine after brain injury may be limited to restoration of sensorimotor ability and not to cognitive functions such as memory. PMID- 1513852 TI - Behavioral performance, brain histology, and EEG sequela after immediate combined atropine/diazepam treatment of soman-intoxicated rats. AB - It is known that rats poisoned with near-lethal doses of pinacolyl methylphosphonofluoridate (soman) develop brain lesions, particularly when convulsions are induced. When rats were intoxicated with a LD50 of soman and treated immediately thereafter with a combination of low doses of atropine and diazepam (LOW AS/DZ treatment), large decrements in performance of an earlier acquired shuttle-box task were found 6 days after intoxication. In contrast, no such decrements were found in soman-intoxicated animals treated similarly with a combination of high doses of these drugs (HIGH AS/DZ treatment). Surprisingly, surviving LOW AS/DZ animals acquired the same task again at a speed that was almost as fast as before intoxication. Similarly treated animals were examined light-microscopically 24 h after intoxication; in LOW-AS/DZ-treated animals, neuropathology was only observed in animals that had exhibited convulsions, whereas in HIGH AS/DZ animals neither convulsions nor brain damage were observed. Power spectra, obtained from electroencephalograms (EEGs) 6 days after intoxication, revealed significant differences between both treatment groups, particularly in the delta-, theta-, and beta-frequencies. After the HIGH AS/DZ treatment, a significant increase in delta activity was found compared to control values, suggestive of neuropathology. It is concluded that, in contrast with the LOW AS/DZ combination, HIGH AS/DZ prevents active avoidance deficits, convulsions, and light-microscopically detectable neuropathology after soman intoxication. However, the results of EEG measurements suggest that some aberrations may still remain even after the HIGH AS/DZ treatment. PMID- 1513853 TI - Effects of bifemelane on discrimination learning of serotonergic-dysfunction rats. AB - To investigate the effect of bifemelane hydrochloride on learning achievements of serotonin-deficient rats, animals were fed with tryptophan-deficient diets and operant type discrimination learning tests were performed. In general, serotonin deficient rats show hyperactivity. In this study, total number of responses in reverse learning experiments was lower in rats that received 50 mg/kg bifemelane compared to the other serotonin-deficient groups. The ratio of correct responses to the total number of responses revealed low learning achievements in the control and low-dose groups, whereas the ratio in the high-dose group was nearly the same as in normal rats in the final few sessions of both the primary and reverse learning experiments. Throughout this study, the high-dose group showed a better improvement in learning achievement than the low-dose group. Therefore, bifemelane has certain effects on learning achievement from a) the functional activation of the serotonergic nervous system and b) changes in neurotransmitter levels in the brain (e.g., acetylcholine, noradrenaline) and overall energy metabolism. PMID- 1513854 TI - beta-Carboline and pentylenetetrazol effects on conflict behavior in the rat. AB - The beta-carbolines and the convulsant agent pentylenetetrazol (PTZ) have been reported as "anxiogenic" in several animal models for anxiety. The present study examined the effects of the beta-carboline noreleagnine (NOR) and PTZ, administered alone and in combination with the benzodiazepine antagonist, Ro 15 1788, on behavior in the conditioned suppression of drinking (CSD) conflict procedure. In daily 10-min sessions, water-deprived female SD rats were trained to drink from a tube that was electrified (0.25 mA). Electrification was signaled by a tone. Acute (20-min) treatment with NOR or PTZ resulted in a dose-dependent decrease in both punished responding (shocks received) and unpunished responding (water intake). Both NOR and PTZ decreased punished responding only at doses that also depressed unpunished responding. Coadministration of Ro 15-1788 (2 mg/kg) reduced the effects of NOR on punished, but not unpunished, responding; this Ro 15-1788 cotreatment reduced the effects of PTZ on both punished and unpunished responding. These data suggest that both PTZ and NOR produce benzodiazepine receptor-mediated anxiogenic-like effects on conflict behavior. PMID- 1513855 TI - Neonatal treatment with clomipramine increased immobility in the forced swim test: an attribute of animal models of depression. AB - The forced swimming test in rats has been identified as a suitable model for detecting antidepressant activity of several drugs regardless of their mode of action. On the other hand, a number of animal models of human endogenous depression have been proposed. Recently, it has been reported that perinatal administration of clomipramine in rats elicits behavioral changes in adulthood that resemble human endogenous depression. In the present study, we showed that in this new animal model of depression immobility was increased when animals were submitted to the forced swimming test. This finding supports the notion that the amount of immobility during the forced swimming test is directly proportional to a depressive state in the rat. PMID- 1513856 TI - Neonatal brain dopamine depletion and the cortical and behavioral consequences of enriched postweaning environment. AB - This study investigated the effects of neonatal intraventricular administration of 6-hydroxydopamine (6-OHDA, 15 micrograms total with and without desmethylimipramine pretreatment) on the cortical thickening and behavioral effects of 35 days of enriched postweaning housing (ENR) in the rat. The 6-OHDA treatment depleted cortical dopamine (DA) to about 40% of control. It did not affect the thickness of the cerebral cortex nor did it affect the capacity for the cortex to be thickened by ENR. In addition, it did not alter the superior performance on two spatial water maze tasks that was caused by ENR. Thus, the potential for neurobehavioral plasticity was not changed by neonatal DA depletion. ENR eliminated the spatial learning/memory deficits that were caused by neonatal DA depletion and that were manifested when the rat was raised in standard (impoverished) laboratory conditions. Hence, environmental factors can modulate the cognitive effects of neonatal DA depletion. ENR did not attenuate the hyperactivity of the neonatal DA-depleted rat. This may reflect the subcortical mediation of this behavioral abnormality. PMID- 1513857 TI - Memory deficits following chronic alcohol consumption in mice: relationships with hippocampal and cortical cholinergic activities. AB - Chronic ethanol consumption (12% v/v for 12 months) produced an accelerated decay of T-maze spontaneous alternation (SA) rates as the interval that elapsed between forced trials, used as acquisition, and a free test trial, used as a retention test, increased. Thus, alcohol-treated mice that exhibited normal SA rates at a short interval (5 min) were impaired at the longer one (6 h) relative to controls. This alcohol-induced deficit was almost completely reversed by physostigmine (0.05 mg/kg, IP) given only before the test trial. Parallel neurochemical analysis showed that chronic alcohol intake produced a significant decrease in hippocampal and cortical sodium-dependent high-affinity choline uptake. In particular, the significant cholinergic activation produced by a T maze exploration in controls was attenuated in experimental subjects so that the between-groups differences already present in the quiet condition were amplified in the active (exploration) state. These findings suggest that the memory deficits induced by chronic ethanol consumption stem from a failure of some cholinergic-dependent retrieval processes. An attempt is made to relate the present results with our previous ones that emphasized the importance of diencephalic damage in alcohol-induced retrieval deficits. PMID- 1513858 TI - Effects of lorazepam on psychomotor performance: a comparison of independent groups and repeated-measures designs. AB - The purpose of this study was to compare the sensitivity to the effects of lorazepam (2.5 mg) of a design using independent groups (random allocation of subjects to either a placebo or a lorazepam treatment) with a repeated-measures design (subjects tested both before and after lorazepam treatment). With both designs, it was possible to demonstrate significant and equal effects of lorazepam in tests based upon speed of responding: Lorazepam significantly increased simple reaction time and significantly decreased performance in number cancellation and symbol copying tasks. The independent-groups design was more sensitive (i.e., showed effects at a higher level of significance) to the lorazepam-induced impairment in episodic memory, as assessed in a picture recognition task, and to the lorazepam-induced impairment in a word completion task. Comparisons between the two control condition scores indicated that there were unlikely to be significant group differences with random allocation of a relative homogeneous group of volunteers, such as medical students. While either design would be appropriate for homogeneous populations, for a heterogeneous clinical population where groups cannot be matched the repeated-measures design would be preferable. PMID- 1513859 TI - Naloxone reduces amphetamine-induced stimulation of locomotor activity and in vivo dopamine release in the striatum and nucleus accumbens. AB - This study tested the possibility that naloxone (NX), an opioid antagonist, reduces the behavioral effects of amphetamine (AMPH) in rats by attenuating the dopaminergic response to AMPH. In the first experiment, adult, male rats were injected SC with either NX (5.0 mg/kg) or saline and 30 min later received doses of AMPH (0.0, 0.1, 0.4, 1.6, and 6.4 mg/kg) cumulatively at 30-min intervals. Gross locomotor counts following AMPH administration were significantly lower for rats pretreated with NX than for rats pretreated with saline. In the second experiment, the same drug treatments were given while performing microdialysis in either the striatum (STR) or nucleus accumbens (NACC). STR rats treated with vehicle showed a larger percentage increase in DA levels following AMPH treatment than did NACC rats treated with vehicle. NX pretreatment did not affect dopamine concentrations in either brain region. However, compared to pretreatment with saline pretreatment with NX significantly decreased the dopaminergic response to AMPH in the STR. There was no difference between the two groups in the peak dopaminergic response to AMPH in the NACC, but there was a significant AMPH x treatment x time interaction due to differences between the groups during the later portion of the response to 6.4 mg/kg AMPH. There was also a difference in locomotor activity following AMPH treatment between NX- and saline-treated subjects during dialysis. These findings suggest that a decrease in the dopaminergic response to AMPH is the mechanism by which NX attenuates behavioral stimulant effects of AMPH. In addition, there is a difference between the STR and NACC in dopaminergic responsiveness to AMPH. PMID- 1513860 TI - Cocaine euphoria, dysphoria, and tolerance assessed using drug-induced changes in brain-stimulation reward. AB - The time course of cocaine-induced changes in self-stimulation thresholds were used to evaluate cocaine euphoria and dysphoria as a function of the chronicity of drug treatment, dosage level, and the spacing of injections. It was assumed that cocaine-induced decreases in thresholds were indicative of cocaine euphoria, while increases in thresholds reflected rebound dysphoric responses to cocaine administration. Three experiments were performed using self-stimulating rats implanted with ventral tegmental area electrodes. Cocaine's threshold-lowering effects were evident 15 min postinjection (IP) with thresholds returning to baseline by approximately 3.0 h after treatment. Little evidence for cocaine induced increases in thresholds was observed during periods of chronic cocaine treatment. However, thresholds were slightly elevated upon withdrawal from chronic cocaine treatment in Experiments 2 and 3. No evidence of tolerance or sensitization to cocaine-induced shifts in thresholds was noted with single daily injections, while multiple daily injections produced tolerance to cocaine's threshold-lowering effects. It is concluded that cocaine's ability to enhance brain-stimulation reward is highly reliable and robust, while decreases in brain stimulation reward associated with chronic cocaine treatment are less reliable and difficult to demonstrate. The possible influence of drug dosage on the induction of cocaine dysphoria and the ability of various self-stimulation procedures to measure dysphoric effects are discussed. PMID- 1513861 TI - Oxiracetam prevents haloperidol-induced passive avoidance impairment in mice. AB - The nootropic drug oxiracetam (50 mg/kg) prevented passive avoidance impairment induced by posttraining administration of haloperidol (0.25 and 0.5 mg/kg). Conversely, oxiracetam did not antagonize either locomotor depression or suppression of active avoidance responses induced by the dopamine receptor blocking agent. The results indicate that prevention of haloperidol-induced retention impairment, by oxiracetam, may be due to a not yet defined protective action, common to other nootropic agents, on different types of experimental amnesias, rather than to a specific interaction with dopaminergic mechanisms. PMID- 1513862 TI - Upregulation of postsynaptic dopamine receptors in the striatum does not influence haloperidol-induced catalepsy in mice. AB - The incidence of haloperidol-induced catalepsy was investigated in mice whose postsynaptic dopamine (DA) receptors in the striatum had been upregulated by denervation with 6-hydroxydopamine (6-OHDA). In nonupregulated mice, which were injected with 6-OHDA 4 days before, DA in the striatum fell to 21% of the level found in vehicle-injected mice but [3H]spiperone binding to the membrane of the striatum did not increase. In upregulated mice, which were injected with 6-OHDA 28 days before, DA was at 24% and [3H]spiperone binding increased by 15%. The ED50 values (with 95% confidence limits) for haloperidol-induced catalepsy in nonupregulated mice and that in upregulated mice was 0.40 mg/kg (0.25-0.65 mg/kg) and 0.29 mg/kg (0.16-0.51 mg/kg), respectively. There was no significant difference in the incidence of catalepsy between the two groups of mice. This suggests that the intensity of catalepsy produced by the DA receptor blockade may be unaltered even when the density of receptors increases. PMID- 1513863 TI - Reversal of testosterone-induced dominance by the serotonergic agonist quipazine. AB - Anabolic steroids and other androgens, such as testosterone propionate (TP), have a facilitatory role in the expression of aggressive behavior. Based upon literature indicating an inverse relationship between aggression and the central neurotransmitter serotonin (5-HT), the present study was undertaken to investigate the role of 5-HT in androgen-induced aggression. In this study, an animal model of aggression involving competition between male rat pairs for sugar pellets was used to investigate the effects of TP. When TP was administered daily (30 mg/kg) to nondominant rats, these animals became dominant. Dominant behavior was found to be stable throughout the study with continued daily administration of TP. To test the serotonergic component of TP-induced aggression, the serotonergic agonist 2-(1-piperazinyl) quinolone dimaleate (quipazine) was administered acutely to TP-dominant rats. Quipazine dose dependently reduced aggressive dominance in TP-dominant rats, as well as in naturally dominant rats. When the serotonergic antagonists pirenpirone or pizotyline were coadministered with quipazine to either group of dominant rats, they blocked the effect of quipazine in reducing dominance. However, when 1-[1H-Indol-4-yloxy]-3 [isopropylamino]-2-propanol (pindolol), a drug that acts at both beta-adrenergic receptors and at 5-HT1A and 5-HT1B receptors, was coadministered with quipazine there was a reversal of the quipazine effect on aggression only in TP-dominant rats. These results indicate that androgen-induced aggression may involve a complex alteration in serotonergic neurotransmission. PMID- 1513864 TI - Effects of chronic morphine administration and naloxone on EEG, EEG power spectra, and associated behavior in two inbred rat strains. AB - Utilizing behavioral and electroencephalographic (EEG) assessments, two inbred rat strains, Lewis (LEW) and Fischer 344 (F344), were exposed to morphine (IV) over a period of 7 days to discern differences in tolerance development. Following morphine injection, the LEW group demonstrated a greater mean total amount, as well as a greater rate of reduction, of stuporous behavior across the 7 days tested. Differences in patterns of latency to onset of slow-wave sleep between the two strains were also exposed. EEG analysis of spectral parameters utilizing an analysis of variance with repeated measures revealed that peak frequency, mean frequency, and edge frequency differed as a function of inbred rat strain. All spectral parameters differed as a function of duration of morphine injection; linear trends were indicated for both strains. Naloxone was administered (IV) following the 7 days of morphine to delineate dependence differences. LEW animals reflected a greater amount of behavioral responses, for example, wet-dog shakes, diarrhea, body stretch, and sluggish behavior. However, F344 rats demonstrated a greater alteration in two spectral parameters assessed: peak frequency and total power. Genetic variability appears to play a major role in both morphine tolerance and dependence as indicated by differences in EEG and behavioral responses. PMID- 1513865 TI - Embryonic differentiation of sexual dimorphism in vasotocin and mesotocin levels in chickens. AB - Chicken embryos of both sexes were injected on the tenth day of incubation with either estradiol benzoate (EB), aromatase inhibitor [1,4,6-androstatrien-3, 17 dione (ATD)], antiestrogen [tamoxifen (TAM)], antiandrogen [flutamide (FLU)], or the oil vehicle as control (C). At adulthood, at the age of 26 weeks, 10 chickens of each sex were killed and the amounts of immunoreactive arginine vasotocin (AVT) and mesotocin (MT) in the anterior hypothalamus (AHA), posterior hypothalamus (PHA), neurohypophysis (NHP), and pineal gland (PNL) were determined. Control hens had significantly more AVT in PNL and less MT in AHA and NHP than the corresponding roosters. This sexual dimorphism was affected by the embryonic treatments; TAM increased AVT in AHA of cockerels but not of hens. In both sexes, TAM and FLU increased AVT content in NYP. In males, but not in females, ATD also increased AVT content in the NHP. TAM and FLU administration to the female embryo reduced PNL AVT to the amount present in normal males. None of the treatments effected AHA MT in hens, while in cockerels TAM increased it. In females, TAM and FLU significantly increased NHP MT to the level of C males. In roosters, ATD, TAM, and FLU increased NHP MT further. In hens, but not roosters, FLU reduced MT in PNL. These results indicate that embryonic differentiation of the MT and AVT systems is affected by gonadal steroids in chickens. PMID- 1513866 TI - Daily dose of ethanol and the development and decay of acute and chronic tolerance and physical dependence in rats. AB - Using behavioral and physiological measures, we compared the rates of development and decay of acute and chronic tolerance to ethanol (ET) and the severity of the withdrawal syndrome. Male rats were treated with 6, 9, or 12 g/kg/day ET or equicaloric dextrin maltose, delivered intragastrically. Although treatment duration varied, the total dose of ET was kept constant at 162 g/kg/rat for the three groups. The effects of a cumulative test dose of ET or equicaloric dextrin maltose, after exposure to a total of 0, 42, 83, 126, and 162 g/kg ET, and at 3, 5, and 7 days after termination of the chronic treatments, were evaluated on rectal temperature, dowel performance, and tail-flick and startle responses. After the initial five tolerance tests, chronic treatments were discontinued and rats were tested in a modified open-field apparatus and for their startle response to an auditory stimulus at 8, 12, 16, 20, 32, and 40 h later. With all measures, little tolerance developed in the 6-g/kg/day group. On the other hand, development of chronic tolerance was fastest in rats treated with the 12 g/kg/dose of ET. Chronic tolerance did not develop to ET's depressant effect on the startle response. Acute tolerance declined with chronicity of treatment in animals given the largest daily dose of ET. During withdrawal, and in contrast to the dextrin maltose-treated animals, there was impairment in all measures taken during the modified open-field test and hypersensitivity of the startle response for all three chronic ET-treated animals. Greatest behavioral impairment occurred in animals treated with 12 g/kg/day, and some impairment was still evident 40 h after the last dose of ET. Thus, the severity of the withdrawal syndrome was greatest in the group displaying the most acute and chronic tolerance. PMID- 1513867 TI - Facilitative effect of carbamazepine on previously induced hippocampal long-term potentiation. AB - The effects of carbamazepine (CBZ) on previously induced hippocampal long-term potentiation (LTP) were examined. Acute experiments were performed on 33 adult, male rabbits. Field potentials in the dentate gyrus were elicited by single shocks to the perforant path, and LTP was induced by tetanic stimulation to the pathway without induction of seizure discharge. At a CBZ serum level of about 5 micrograms/ml (value +/- SD = 5.40 +/- 1.28 micrograms/ml), the previously induced LTP in population spikes (PSs) and population excitatory postsynaptic potentials (EPSPs) was facilitated. At a CBZ serum level of about 15 micrograms/ml (value +/- SD = 14.28 +/- 1.29 micrograms/ml), the LTP in PS alone was decreased. The effects of carbamazepine on synaptic inhibition were examined by the paired-pulse test. The inhibition was enhanced with induction of LTP. After administration of CBZ, at a CBZ serum level of about 5 micrograms/ml the inhibition was further enhanced, while it was attenuated at a CBZ serum level of about 15 micrograms/ml. These results suggest that CBZ has a facilitative effect on previously induced LTP. PMID- 1513868 TI - Administration of dexfenfluramine in pregnant rats: effect on brain serotonin parameters in offspring. AB - Dexfenfluramine (DFEN) was infused SC at doses of either 6 or 12 mg/kg/day during the last week of pregnancy in rats. Compared with untreated controls, weight gain of dams was attenuated by DFEN without effect on the number or birth weight of offspring. Brain serotonin (5-HT) concentration and/or paroxetine binding to the 5-HT uptake carrier was reduced by 20% on the day after birth in one study but not in two other studies. No decreases in brain 5-HT parameters were observed on or after the sixth postnatal day. In contrast, mothers sustained large depletions of brain 5-HT when measured at least 3 weeks after giving birth. These data indicate that fetal brains either are protected from or recover rapidly from the 5-HT-depleting actions of high-dosage regimens of DFEN in rats. PMID- 1513869 TI - Effects of piracetam on retention and biogenic amine turnover in albino rats. AB - The chronic effects of orally administered 2-pyrrolidone acetamide (piracetam) on one-trial, passive avoidance task were studied in albino rats. The effects on the contents of norepinephrine (NE), dopamine (DA), and serotonin (5-HT) in the brain and on the levels of their metabolites both in the brain and urine were also assessed. Significant improvement was observed in the retention ability compared with saline-administered controls. The contents of NE, DA, and 5-HT and their metabolites in the brain were significantly decreased after piracetam administration. The urinary metabolite levels were also significantly decreased except total 3-methoxy-4-hydroxyphenyl glycol (MHPG). These data indicate that piracetam causes an overall decrease in the turnover of central monoamines. Thus, the results of this study implicate the involvement of NE, DA, and 5-HT systems in learning and memory processes. Piracetam did not exert any GABAergic effect as shown by the absence of change in the brain GABA levels. PMID- 1513870 TI - Effects of d-amphetamine and ethosuximide on responding under delayed-matching-to sample procedures with differential and nondifferential outcomes. AB - Pigeons were exposed to delayed-matching-to-sample (DMTS) procedures in which food or a flash of the feeder light followed correct responses. When these consequences were correlated with a particular stimulus (e.g., food followed matching responses to red and a flash of the feeder light followed matching responses to green), accuracy was higher (i.e., stimulus control was greater) than when discriminative stimuli and consequences were not correlated. Although stimulus control in the absence of drug appeared to be weaker under the uncorrelated procedure, neither d-amphetamine (0.5-3.0 mg/kg) in Experiment 1 nor ethosuximide (40-160 mg/kg) in Experiment 2 disrupted accuracy to a greater extent under that procedure. These results, like those of a prior investigation, suggest that drug effects are similar under DMTS procedures regardless of whether correlated or uncorrelated outcomes are arranged. PMID- 1513871 TI - Muscimol facilitates sexual receptivity in hamsters when infused into the ventral tegmentum. AB - Progestogenic stimulation of both the ventral medial nucleus of the hypothalamus (VMH) and the ventral tegmental area (VTA) within the midbrain is critical for normal receptivity in female hamsters. However, few estrogen-induced progestin receptors have been found in the midbrain. In addition, recent evidence suggests that progestin's action in the VTA is mediated nongenomically at the membrane. The present experiment investigated the possible role of GABAA receptors in mediating the effects of progesterone in this brain region. Ovariectomized female hamsters were bilaterally implanted with chronic cannulae aimed toward the ventral mesencephalon. Five days after surgery, animals were injected with 10 micrograms estradiol benzoate SC. Forty hours later, the same animals were injected with either 25 or 100 micrograms progesterone and at hour 43.5, 50 ng muscimol was infused in 0.5 microliters. Control animals received 0.5 microliters vehicle, sterile saline, or no infusion. At hour 44, animals were tested for sexual receptivity by placing them in an observation arena with a sexually experienced male for 10 min, during which lordosis duration was recorded. The following week, the same regimen was given with the alternate dose of progesterone. Histology revealed that only those animals that were infused with muscimol into the VTA had total lordosis durations that were significantly longer than the controls. Implants that missed the ventral tegmental area were much less effective. These results indicate that GABA might play a facilitatory role in enhancing the efficacy of threshold doses of progesterone. Whether this interaction is due to a direct effect of progestins on the GABAA receptor complex awaits further study. PMID- 1513872 TI - Cocaine's colocalized effects on synaptic serotonin and dopamine in ventral tegmentum in a reinforcement paradigm. AB - The effect of subcutaneous (SC) cocaine (20 mg/kg) on synaptic concentrations of the biogenic amines, dopamine (DA), and serotonin (5-HT) in Ventral Tegmental Area, (VTA-[A10]) was studied in freely moving and behaving rats (rattus norvegicus) with in vivo voltammetry (in vivo electrochemistry). The actual detection of the biogenic amines was on-line and within a temporal resolution of seconds. Simultaneously, the psychostimulant behavior induced by cocaine was studied by infrared photocell beam detection. The results show that cocaine concurrently and significantly increased synaptic concentrations of DA (p less than 0.0001) and 5-HT (p less than 0.004) in VTA. Serotonin changes were accompanied by a notable oscillatory pattern. Importantly, DA and 5-HT changes in VTA were significantly and positively correlated (p less than 0.01). Moreover, psychostimulant behaviors induced by cocaine were significantly increased over control values (p less than 0.0001). Psychostimulant behaviors were significantly correlated with concurrently changing synaptic concentrations of DA (p less than 0.01) and also with 5-HT to a lesser degree. Additionally, behavioral data indicate that cocaine may exhibit an anxiolytic effect during acute administration because agoraphobic behavior, as shown by increased central ambulatory behavior, was dramatically reduced by cocaine. Summarily, the present findings show that cocaine increased synaptic concentrations of DA in VTA, an action that is correlated with cocaine-induced psychostimulant behavior. The DA ergic effect appears to be tonically maintained. Furthermore, new findings demonstrate a colocalized, cocaine induced 5-HT-ergic effect in VTA, which keeps pace with cocaine-induced alterations in DA-ergic neurotransmission. Thus, 5-HT may be a relay or a gating mechanism for a DA reward signalling pathway for cocaine. PMID- 1513873 TI - Anticonvulsant effect of allopurinol on hippocampal-kindled seizures. AB - This study assessed the anticonvulsant effect of allopurinol (5 and 50 mg/kg, IP) on seizures kindled from the feline hippocampus. Allopurinol at a higher dose significantly reduced the behavioral seizures stage, but not afterdischarge duration, without producing any behavioral toxicity. The present results lend experimental support to the contention that allopurinol possesses anticonvulsant efficacy in the treatment of human epilepsy. PMID- 1513874 TI - Mobilization and location of the genetic determinant of chloramphenicol resistance from Lactobacillus plantarum caTC2R. AB - The mobilization of a nonconjugative plasmid (pCaT) that mediates chloramphenicol resistance in Lactobacillus plantarum caTC2R was achieved by comobilization with the conjugative plasmid pAM beta 1. The conjugation studies confirmed that the 8.5-kb pCaT in L. plantarum caTC2R contains the gene responsible for chloramphenicol resistance and that the plasmid has several unique restriction sites which make it useful for genetic studies in Carnobacterium spp. Cloning studies showed that the gene responsible for chloramphenicol resistance is located in the 2.6-kb EcoRV-SalI region of pCaT. This was confirmed by probing the 3.0-kb BglII fragment of pCaT with a biotin-labeled 1.6-kb BstEII-HpaII fragment from the streptococcal-derived plasmid pVA797(Cmr). Expression of chloramphenicol resistance in Carnobacterium as well as in other Lactobacillus species was achieved by electrotransformation using donor DNA from pCaT. PMID- 1513875 TI - Use of differential agar media for detection of cloned DNA fragments in the tetracycline and chloramphenicol resistance genes of pBR322. AB - A method for detecting newly cloned DNA fragments in pBR322-based vectors was devised for use in DNA probe production. Escherichia coli strain DH5 containing plasmids with different resistance patterns to tetracycline (Tc) and chloramphenicol (Cm) were grown on nonpigmented media, blotted, transferred, and incubated for 2 h on MacConkey agar containing Tc or Cm. Resistant colonies changed color to pink as they began fermenting the lactose on the agar, while sensitive colonies remained white but were still viable and could be subcultured. This method can be applied to the detection of other plasmids with insertional inactivation of Tc or Cm resistance marker genes following successful cloning experiments, especially if pUC18 or M13 is not a possible vector. It eliminates 1 day of culture and the labor involved in individually transferring hundreds of colonies. PMID- 1513876 TI - Genetic and molecular analysis of pIP417 and pIP419: Bacteroides plasmids encoding 5-nitroimidazole resistance. AB - This report describes a genetic and molecular analysis of two transferable Bacteroides plasmids, pIP417 and pIP419, which carry genetic determinants conferring low-level resistance to 5-nitroimidazoles. The restriction endonuclease cleavage sites for each plasmid were localized. The NiR genetic determinants of pIP417 and pIP419 plasmids have been cloned into the Bacteroides cloning vector pBI191 (C.J. Smith, J. Bacteriol. 164, 294-301, 1985) as PvuII and Sau3A fragments, respectively. Both inserts had different restriction sites and did not cross-hybridize by Southern blot analysis. Genetic data obtained by cloning into pBI191 clearly show that the PvuII-generated fragments A (Rep) and B (Mob) of pIP417 are involved in plasmid replication and transfer, respectively. Although encoding resistance to the same antibiotic, both plasmids appeared different with regard to the 5-nitroimidazole resistance and replication genetic determinants. However, they share a homology in a region involved, at least in one case, in plasmid transfer. Considering the spontaneous high level of resistance to 5-nitroimidazole in Escherichia coli, this work, based on direct gene cloning into Bacteroides, demonstrates the value of such an approach. PMID- 1513877 TI - Construction of a cassette enabling regulated gene expression in the presence of aromatic hydrocarbons. AB - A high-level expression cassette has been constructed from a TOL plasmid derived from Pseudomonas putida carrying all cis- and trans-acting regulatory elements necessary for transcriptional gene activation in the presence of aromatic hydrocarbons such as toluene. Foreign DNA can be inserted at unique KpnI, SacI, and EcoRI sites 7, 13, and 15 nucleotides downstream of a ribosome binding site. The cassette, flanked by BamHI and EcoRI restriction sites, was inserted into a broad-host-range vector and its efficacy demonstrated in various purple bacteria by monitoring the expression of a reporter gene spectrophotometrically and by SDS PAGE. High-level induction (80- to 600-fold) was detected in Enterobacteriaceae and in Pseudomonas but was absent or low in Agrobacterium tumefaciens and Rhizobium leguminosarum. PMID- 1513878 TI - Construction of a sequenced Clostridium perfringens-Escherichia coli shuttle plasmid. AB - A new Clostridium perfringens-Escherichia coli shuttle plasmid has been constructed and its complete DNA sequence compiled. The vector, pJIR418, contains the replication regions from the C. perfringens replicon pIP404 and the E. coli vector pUC18. The multiple cloning site and lacZ' gene from pUC18 are also present, which means that X-gal screening can be used to select recombinants in E. coli. Both chloramphenicol and erythromycin resistance can be selected in C. perfringens and E. coli since pJIR418 carries the C. perfringens catP and ermBP genes. Insertional inactivation of either the catP or ermBP genes can also be used to directly screen recombinants in both organisms. The versatility of pJIR418 and its applicability for the cloning of toxin genes from C. perfringens have been demonstrated by the manipulation of a cloned gene encoding the production of phospholipase C. PMID- 1513879 TI - Location of the origin of replication for the 7.5-kb Chlamydia trachomatis plasmid. AB - The hypothetical origin of replication for the 7.5-kb plasmid common to Chlamydia trachomatis is believed to be in a region of the plasmid that contains four 22-bp tandem repeats preceded by an A-T-rich region. To test this hypothesis, replication of plasmid DNA in metabolically active reticulate bodies of the Lymphogranuloma venereum biovar of C. trachomatis was examined by electron microscopy. The results presented show that the origin of replication appears to be near the tandem repeats of pCHL2. In addition, replication of the 7.5-kb plasmid is unidirectional, and the copy number during replication is 7-10. The evidence presented suggests that C. trachomatis has a homologue to the Escherichia coli dnaA gene and that this homologue might be involved in replication of the C. trachomatis 7.5-kb plasmid. PMID- 1513880 TI - New plasmid vector and host system for genetic engineering in Bacillus sphaericus. AB - A new plasmid, pNQ116, was constructed in Bacillus sphaericus by cloning a promoter fragment from B. sphaericus Ts-1 into pNQ112. The plasmid (CmrKmr, 5.23 kb) contains a restriction endonuclease polylinker used for cloning foreign genes, and its cat-86 gene is expressed at high levels from the Ts-1 promoter. This plasmid vector has been transformed into B. sphaericus AS 1.270, AS 1.465, AS 1.469, and 2362, at frequencies of 10(2)-10(3) transformants per microgram of DNA, and is maintained stably under nonselective conditions in these host strains. The presence of pNQ116 in B. sphaericus 2362 does ot interfere with the mosquito larvicidal activity of the organism. PMID- 1513881 TI - Molecular analysis of a gene from Bacteroides fragilis involved in metronidazole resistance in Escherichia coli. AB - The region of Bacteroides fragilis DNA on the recombinant plasmid pMT100 responsible for conferring metronidazole resistance in Escherichia coli strains was characterized. An open reading frame (ORF1) of 195 bp encoded a protein of 64 amino acids with a predicted M(r) of 7.3 kDa. Deletion analysis indicated that ORF1 conferred the metronidazole resistance phenotype and encoded a protein with an apparent M(r) of approximately 8-10 kDa. PMID- 1513882 TI - Auricular repair with autogenous rib cartilage grafts: two decades of experience with 600 cases. AB - The purpose of this paper is twofold: to present a sound approach to auricular construction using methods that have evolved through two decades of my personal experience with 600 cases and to discuss pertinent information I have gleaned from a questionnaire sent to my operated patients. This series comprises 546 completed ears in 500 microtia patients (46 bilateral) and 75 completed ears in acquired deformities. Follow-up ranges from 1 to 17 years. Major complications such as infection, hematoma, or skin loss with cartilage exposure occurred in only 1.6 percent of cases and were limited to the perioperative period of 12 days. None have occurred in the last 9 years (481 frameworks). This paper describes the evolution and rationale for my current management of total ear repair and covers preoperative planning, how to fabricate the rib cartilage framework, how to modify the framework for specific deformities, and how to cover the framework, i.e., how to assess and use local skin and vestiges or when to supplement the coverage by recruiting fascial flaps or using tissue expansion. When considering fascial flaps, patient selection was found to be particularly important because of long-term effects on the donor scalp; expansion was found to be most useful intraoperatively. This paper also covers how to manage the hairline, how to stage the surgery, when to combine procedures, and how to manage bilateral microtia in a team approach. The survey revealed that autogenous cartilage frameworks grow, are durable, retain their detail over the years, and withstand trauma well. More than 40 severe traumas occurred in surgically constructed ears, and all healed without incident. Ears constructed in young patients generally grew to keep pace with the opposite normal side; 41.6 percent actually overgrew by several millimeters. Emotional and psychological benefits were universal, and patient satisfaction was high. Among patients who were classified as "severely affected" by the original deformity, 100 percent were pleased with the result. When considered "moderately disturbed" by the microtic defect and operated on by age 14, 95.5 percent of patients were satisfied with the surgical repair; 83.3 percent of adolescents between the ages of 15 and 20 who did not consider themselves "severely affected" by the deformity were pleased with the outcome, and the rest were "undecided." PMID- 1513883 TI - Intracranial pressure and intracranial volume in children with craniosynostosis. AB - Intracranial volume and intracranial pressure have been measured in 66 children with craniosynostosis, 48 boys and 18 girls. The premature fusion of skull sutures is assumed to restrict skull growth and predispose to elevated intracranial pressure. Thirteen children (20 percent) had raised intracranial pressure and demonstrated a significant restriction of skull growth. In this series, volume measurement alone, however, did not serve as a reliable predictor that the intracranial pressure was raised. PMID- 1513884 TI - Primary reconstruction of major human bite wounds of the face. AB - Primary reconstruction of 36 major human bite wounds of the face without clinical infection has been carried out successfully as late as the fourth day after the initial injury. Primary healing was achieved in all patients. The postoperative period was free from major infection in all patients except one, including the latecomers. Extensive bacteriologic studies reveal that the infection in human bite wounds occurs secondarily as invasion to devitalized tissue. We therefore consider that debridement of wound edges to eliminate the crushed devitalized tissue is the key to success. PMID- 1513885 TI - Reconstruction of the lacrimal excretory system. AB - Primary surgical repair of the lacrimal drainage apparatus may not be feasible in patients with maxillofacial injuries involving extensive structural damage. If secondary restoration of the tear duct is not possible, reconstruction of an aberrant passage then will be necessary for tear drainage. Although the Pyrex conjunctivorhinostomy has been considered to be the most effective modality of treatment in managing patients with tear-duct dysfunction, this procedure can be plagued with problems of tube dislodgment, infection, and cicatricial tract obliteration. The patients are, furthermore, required to wear the device for the remainder of their lives. Autologous material is therefore best suited for reconstructing a conduit. A medially based mucosal flap fashioned in the lower palpebral conjunctiva, 5 mm in anteroposterior dimension and 15 mm in horizontal length, can be used to form a conduit. This is then sutured to a flap mobilized from the nasal cavity, the lacrimal sac, or the maxillary antrum. In the past 15 years, a total of 24 fistulous tracts utilizing this technique were reconstructed in 20 patients with tear-duct obstruction. The experience accumulated from managing this group of patients forms the basis of this report. PMID- 1513886 TI - Distant effects of dorsal and tip grafting in rhinoplasty. AB - Grafts to the nasal dorsum and tip, whose local effects are well known, also have distant effects that may not be as readily obvious but that nevertheless are just as real. Dorsal and tip grafts can shorten or lengthen the nose (relatively and absolutely), affect nasal symmetry, preserve or alter nasal ethnic characteristics, and alter dorsum/tip relationships. Each of these properties increases the utility of cartilage and bone grafts in treating a variety of nasal configurations. PMID- 1513887 TI - A new intraoral flap: facial artery musculomucosal (FAMM) flap. AB - By combining the principles of nasolabial and buccal mucosal flaps, we have designed a new axial musculomucosal flap based on the facial artery. This flap has been designated the facial artery musculomucosal (FAMM) flap. The flap has proven to be reliable either superiorly based (retrograde flow) or inferiorly based (antegrade flow). It is versatile and has been used 18 times in 15 patients, with one failure and two partial losses. It has been used successfully to reconstruct a wide variety of difficult oronasal mucosal defects, including defects of the palate, alveolus, nasal septum, antrum, upper and lower lips, floor of the mouth, and soft palate. PMID- 1513888 TI - Argon laser treatment of port-wine stains: the patients' evaluations of the result. AB - The argon laser is now a well-established method of treating port-wine stains (PWS) in the face and neck areas. Satisfactory results are reported in 44 to 75 percent of cases, but criteria for that classification and the patients' perceptions of the result are seldom given. In the present paper, a sample of 58 patients was used to assess the patients' own perceptions of the degree of lightening and scarring. Three felt the results were excellent, 23 good, 18 fair, and 14 poor. The treatment was considered as unpleasant by 76 percent, and 55 percent of the patients asked for a new consultation. Scarring was noticed by 50 percent. The patients' perceptions of the results and physicians' rating were the same in 69 percent. The best results were obtained in older patients with small port-wine stains. Such lesions also can be treated surgically with good results. PMID- 1513889 TI - Cryosurgery of lentigo maligna. AB - Lentigo maligna denotes flat, pigmented lesions predominantly in areas of actinic damage that have the propensity to become malignant. More than 10 years may pass before lentigo maligna evolves into an invasive neoplasma. As an invasive process, it is termed lentigo maligna melanoma (LMM), and it has the potential for both lymphatic and hematogenic metastases. Because of the size and location of the lesions, cosmetically unsatisfactory scars may result from conventional surgery. Therefore, alternative means of treatment, including cryosurgery, have been employed. We report on 12 patients suffering from lentigo maligna who had been treated successfully by cryosurgery between 1984 and 1990. The average follow-up period was 51.4 months, and the recurrence rate was 8.3 percent. Knowing that microinvasive components can be demonstrated in 15 percent of lentigo maligna lesions, we retrospectively reassessed our patients by immunohistochemical procedures with S-100 protein. Although intradermal microinvasion could be confirmed in one patient, no recurrence had been observed within 61 months of follow-up. Provided that patients are selected properly and extension of cryonecrosis is monitored, cryosurgery may prove an efficient alternative to conventional surgery in the treatment of lentigo maligna. PMID- 1513890 TI - Acute intraoperative arterial lengthening for closure of large vascular gaps. AB - This study demonstrates the feasibility of acute extraluminal expansion to elongate arteries intraoperatively in order to overcome defects too large to be repaired primarily. Twenty Sprague-Dawley rats were divided into two groups: an expander-elongation group and a nonexpanded control group of 10 rats each. Arterial resections were performed ranging from 6 to 22 mm. A miniaturized tissue expander was used to stretch vessels in three consecutive cycles over a 15- to 20 minute period (expander-elongation group). Defects twice as long as those which could be overcome by mobilization alone (nonexpanded control group) could be closed following the application of this technique without thrombosis. Initial laboratory findings and the application of this method in a clinical case are presented. PMID- 1513891 TI - Method for the construction of sphincters in the human body: the birth of a new kind of medicine. PMID- 1513892 TI - Pancake ear: an occupational hazard. PMID- 1513893 TI - Reconstruction of one-third plus of the auricular circumference. PMID- 1513894 TI - Progressive hemifacial atrophy associated with Lyme disease. AB - A case is described of progressive hemifacial atrophy occurring in a child with Lyme disease. Borrelial infection may have been an etiologic factor in the progressive hemifacial atrophy, which was ultimately treated with an SIEA free flap transfer. PMID- 1513895 TI - Pseudomeningocele: an unusual complication of craniofacial surgery. AB - A previously unreported complication of pseudomeningocele following monoblock frontofacial advancement is described. The defect was repaired by means of an extracranial approach with a satisfactory outcome. PMID- 1513896 TI - Bilateral rotated buttock flaps for vaginal atresia in severely masculinized females with adrenogenital syndrome. AB - The addition of large bilateral rotated buttock flaps to the flap vaginoplasty enhances the introitus in severely masculinized patients with high vaginal atresia. The flaps are rotated medially to create the distal aspect of the lateral and anterior vaginal wall. The inferior advancement of the labioscrotal folds aids in closing the donor defect, while at the same time creating the appearance of labia majora. Finally, the use of these local tissues will result, in later life, in a vaginal reconstruction free of unwanted hair. This reconstruction technique should obviate dilatation in the older child and prevent further stenosis. PMID- 1513897 TI - Technique of foot lengthening and shaping with free vascularized iliac osteocutaneous flap. AB - The iliac osteocutaneous flap has been used widely to replace bony defects of the mandible and the extremities. We report a further application of this flap in foot reconstruction. The iliac osteocutaneous flap proved to be of value to augment both soft tissue and bone in a transmetatarsally amputated foot. This resulted in satisfactory function and an appealing cosmetic result, allowing the patient to wear normal shoes. Flap design and secondary contouring procedures are described for the success of this reconstruction. PMID- 1513898 TI - An unusual pediatric lymphoma. AB - The diagnosis of true histiocytic lymphoma is complex. Since clinical findings are nonspecific and histopathology is only suggestive, misdiagnosis is likely. Using appropriate cytochemical and immunologic markers incorporated into a panel of studies, the diagnosis of true histiocytic lymphoma may be secured. Only with accurate diagnosis and further study can long-term, disease-free survival and curability be determined. PMID- 1513899 TI - Maximizing gain from rectangular tissue expanders. AB - Three different options are proposed to cut the flap after expansion of rectangular tissue expanders. Each method, when used effectively, allows the expander to deliver the full punch of the expansion process. PMID- 1513900 TI - Multipurpose anthropometric facial anglemeter. AB - We have developed a multipurpose anglemeter for measuring the face that enables us to determine accurately the size of six profile angles by both direct and indirect anthropometry in markedly reduced time. PMID- 1513901 TI - The leech amphitheater for digital replantation. PMID- 1513902 TI - Silicone genital prosthesis for female-to-male transsexuals. AB - In the case of a female-to-male transsexual who has not yet undergone phalloplasty, one of the greatest concerns is how to give the appearance of having male external genitals. Many methods have been attempted by patients. We helped develop a silicone prosthesis after obtaining information on the demands of female-to-male transsexuals through a questionnaire sent to 120 of them. Three different models of the prosthesis were designed to enable three different methods of fixation. One of the methods of fixation involves the creation of a bipedicled skin flap in the pubic area. Thus this is the first of such prostheses that can be worn directly fixed to the body. It seems that the prosthesis developed in close cooperation with our department fulfills most of the needs of our patients. PMID- 1513903 TI - Vulva reconstruction with a tissue expander. AB - A patient with exstrophy of the bladder in whom we performed vulva reconstruction using a tissue-expansion technique and local flaps was presented. The ultimate result was in concert with the anatomic characteristics of normal external genitalia with regard to type of skin, pigmentation, hair pattern, quality of circulation, and sensory supply. PMID- 1513904 TI - The role of the gastrointestinal tract in the development of burn sepsis. AB - Conceptualization of the gastrointestinal tract as the "motor" that drives sepsis and multiple-system organ failure has only recently been appreciated. Most of the investigation into the pathophysiology of gut-derived sepsis involves using animal models; however, some of the findings are already being corroborated in human studies. The gastrointestinal tract is a dynamic organ whose function as a front-line defense against infection needs to be appreciated. The development of lethal sepsis is a function of the microbial load and virulence, the status of the gastrointestinal barrier, and the magnitude of the host defense response. In assuming care of a critically ill patient, we must be judicious in the use of antibiotics in order to prevent intestinal overgrowth of potential pathogens. Providing proper nutrition by an enteral route (when possible) not only satisfies caloric needs but regulates the microflora and maintains the integrity of the mucosal barrier. Burn patients should receive enteral nutrition early, the first day if possible. This not only will protect the intestinal mucosa but also will blunt the hypermetabolic response following thermal injury. Lastly, the patient should not receive an excessive amount of narcotic or sedative, for these drugs have an inhibitory effect on gastrointestinal motility, encouraging bacterial overgrowth. In the near future, new therapeutic modalities may soon become available to protect and treat the compromised gastrointestinal barrier. These modalities may include, but certainly are not limited to, the use of glutamine and xanthine oxidase inhibitors to prevent stress-related injury to the gastrointestinal mucosa.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1513905 TI - The effect of epinephrine on blood loss during suction lipectomy. PMID- 1513906 TI - Iliac node dissection for stage II melanoma. PMID- 1513907 TI - Treating capsular contracture. PMID- 1513908 TI - Proximal interphalangeal joint ear cartilage grafts. PMID- 1513909 TI - [Group dynamics and psychopathology of schizophrenic patients in a day care setting]. PMID- 1513911 TI - [Bone mineral density in epileptic patients receiving antiepileptic drugs- measurement by dual photon absorptiometry]. PMID- 1513910 TI - [Clinical electroencephalographic studies of suicide attempts in psychiatric patients]. PMID- 1513912 TI - [The right to treatment of the institutionalized mentally ill in the United States]. AB - In his epochmaking article, Birnbaum proposed that courts should recognize a right to treatment of institutionalized psychiatric patients based on the substantive due process. His proposal was adopted in Rouse v. Cameron as a statutory right. Wyatt v. Stickney decision was the first to hold that there was a constitutionally based right to treatment for involuntarily committed patients. The Supreme Court, though reluctantly, held in Youngberg v. Romeo that the institutionalized mentally retarded were entitled to minimally adequate training, which was drawn in the Fourteenth Amendment. PMID- 1513913 TI - Proceedings of the 31st annual meeting of the New Clinical Drug Evaluation Unit (NCDEU). Key Biscayne, Florida, May 28-31, 1991. PMID- 1513914 TI - Cognitive behavior therapy and relapse of nonbipolar depression: parallels with pharmacotherapy. AB - The risk of relapse was studied in 44 major depressives following successful acute treatment with cognitive behavior therapy (CBT). Patients entered a 1-year prospective followup with independent clinical assessments at 1, 3, 6, 9, and 12 months. Of these patients, 15 (34%) relapsed; correlates included marital status, recurrent subtype, higher initial and residual ratings of depressive severity, and slower response to therapy. Both married status (p = .008) and fully recovered status (p = .02) were significantly and independently related to decreased risk of relapse using the Cox proportional hazard method. These findings provide further documentation of a relationship between residual symptomatology and relapse after cessation of active treatment and closely parallel findings pertaining to risk of relapse after acute antidepressant pharmacotherapy of unipolar depression. As in pharmacotherapy, a longer period of continuation treatment may be indicated for patients at risk for relapse after an initial course of time-limited therapy with CBT. PMID- 1513915 TI - Pharmacotherapy observed in a large prospective longitudinal study on anxiety disorders. AB - Data concerning 331 subjects participating in a longitudinal study on anxiety disorders were collected over the first 6 months of the study. Preliminary analyses of somatic treatment according to diagnoses and study site were conducted. The comorbidity of one anxiety disorder with other DSM-III-R diagnoses and other types of anxiety disorders was extensive. Patients with panic disorder received significantly more treatment with a benzodiazepine than patients without panic disorder. Fewer than five percent of the sample were treated with a monoamine oxidase inhibitor. Comorbid depression increased the likelihood of treatment with a newer non-MAOI (non-monoamine oxidase inhibitor), nontricyclic antidepressant. Results suggest a strong effect of treatment site on the pharmacotherapy offered. PMID- 1513916 TI - Fluoxetine for trichotillomania: an open clinical trial. AB - Of 17 adult patients with long-standing trichotillomania, 13 completed an 8- to 12-week open trial of fluoxetine, up to 80 mg per day. No patient had obsessive compulsive disorder or major depression. We used the compulsions subscale of the Yale-Brown Obsessive-Compulsive Scale (YBOCS) to rate patients' hair-pulling behavior. The 13 completing patients' mean YBOCS score decreased significantly from 10.15 at baseline to 5.92 at the completion visit (Student's paired t = 4.82, df = 12, two-tailed p less than .001). Of these 13 patients, 5 experienced a 50 percent or greater decrease in their pulling behavior as measured by the YBOCS; 4 experienced between a 25 percent and 50 percent decrease. Three of the patients stopped pulling entirely, as did 2 of the 4 noncompleting patients. Three noncompleting patients discontinued treatment because of side effects, and 1 insisted on early use of behavior therapy. Comparative treatment trials elucidating the indications, risks, and expectable benefits of psychotherapeutic and pharmacological treatments are needed. PMID- 1513917 TI - The efficacy of psychotropic drugs: implications for power analysis. AB - The estimation of the correct sample size to successfully test a hypothesis has become critical. A common approach to this problem is for the investigating team to complete a pilot study of a few patients to establish the "active drug placebo" difference, using this "effect size" to perform the power analysis for sample size estimation. Given the variability evident in the effect size from completed and published studies, the pilot study approach may not be entirely dependable. The authors propose a method to obtain this initial "active drug placebo" difference, in the field of psychotropic drug research. They apply meta analysis to statistically summarize effect sizes obtained from an exhaustive review of the literature for a specific psychotropic drug in a given clinical condition. All double-blind, random assignment studies are used to calculate the effect size; therefore, no selection bias exists. These literature-based effect sizes are then used to perform the traditional power analysis for sample size estimation. The authors propose these estimations as a convenient reference source for future clinical investigators. PMID- 1513918 TI - Predictors of placebo response: a retrospective analysis. AB - This retrospective evaluation involved 197 patients from independent clinical investigations of four antidepressant medications. Six variables were analyzed for their discriminative utility in predicting placebo response rates: gender; marital status; age; education; duration of illness; and severity of depressive symptomatology, as measured by Hamilton Rating Scale for Depression (HAM-D or HDRS) scores. Men were slightly more responsive to placebo than were women (29.8%, n = 94 vs. 24.3%, n = 103). Married patients demonstrated the highest probability of a positive placebo response (38.15%, n = 76), as compared with widowed/separated/divorced (21.9%, n = 73) or single (16.7%, n = 48) patients. A trend toward an increased probability of placebo response was detected for patients aged 60 and above (35.7%, n = 14). Educational level achieved and duration of illness were not predictive. Severity of illness proved most noteworthy, with the placebo response rate higher in the more mild patients (40.8%, n = 27 vs. 23.4%, n = 77). PMID- 1513919 TI - Debrisoquine hydroxylation phenotyping in geriatric psychopharmacology. AB - The metabolic ratios (MRs) between debrisoquine (DBQ) and 4-hydroxydebrisoquine in urine after a single dose of 10 mg DBQ was determined in 175 unmedicated, healthy subjects older than age 59 (mean of 75 years). Creatinine clearance was determined on the same 8-hour urine collection. Test procedures were well tolerated in all cases. Although age was significantly correlated with creatinine clearance (r = -.38), there was no relationship between age and MR. Analysis by kernel density estimation revealed a bimodal distribution of MRs with an antimode of 11.6. Six subjects (3.4%) were categorically slow DBQ metabolizers (MR greater than 11.6). The proportion of elderly slow metabolizers approaches the lower range determined in a younger population. Our findings, that DBQ oxidative metabolism does not necessarily change with aging, alone, and that (genetic) slow DBQ metabolizers endure into old age, remaining at risk for treatment with many commonly used psychotropics, suggests the need to study the relevance of metabolic phenotyping in elderly psychiatric patients. PMID- 1513920 TI - Low dose oral haloperidol and blood levels in Alzheimer's disease: a preliminary study. AB - Nineteen patients with probable Alzheimer's disease who manifested psychosis or behavioral disturbance received 0.5 to 5 mg per day of oral haloperidol, with blood levels drawn on a stable daily dose. Oral dose correlated strongly with haloperidol blood levels assessed by radioimmunoassay (r = 0.82, p = .0001). The stronger correlation observed between oral dose and blood level compared with most studies in schizophrenia may be related to the fact that virtually all the Alzheimer's patients were neuroleptic naive, without the alterations in absorption and metabolism known to occur in schizophrenics receiving long-term neuroleptic treatment. Compared with oral dose, blood levels showed stronger relations to changes in symptoms and to changes in severity of extrapyramidal side effects. These preliminary data suggest that the utility of monitoring haloperidol blood levels in patients with Alzheimer's disease merits further investigation. PMID- 1513921 TI - Blocking the Ca(2+)-activated cytotoxic mechanisms of cholinergic neuronal death: a novel treatment strategy for Alzheimer's disease. AB - The major neuropathological finding in Alzheimer's disease (AD) is the death of cholinergic cell bodies originating in the nucleus basalis of Mynert. This paper will review the data suggesting that a pharmacologic strategy designed to slow the rate of cholinergic neuronal death (CND) should be of palliative value in the treatment of AD. Recent data on the biology of cell death (CD) show that there are two patterns of CD: necrosis and apoptosis or genetically controlled, programmed cell death. Regardless of whether cells die by necrosis or apoptosis, four Ca(2+)-activated cytotoxic mechanisms are triggered. Cytosolic free [Ca2+]i increases with aging. After 75 years, this rise may lead to the activation of a putative apoptotic gene in AD that results in CND. Since the increase in cytosolic [Ca2+]i may be mediated by the voltage operated L-type Ca2+ channel on the neuronal cell body, chronic treatment with an L-channel blocker, like nimodipine, might palliate the progression of and possibly prevent the majority of cases of AD. PMID- 1513922 TI - Haloperidol in schizophrenic children: early findings from a study in progress. AB - This report presents preliminary findings in an ongoing double-blind, placebo controlled study of the safety and efficacy of haloperidol in hospitalized schizophrenic children. The subjects are diagnosed schizophrenic by DSM-III-R criteria and admitted to the Bellevue Hospital Children's Inpatient Psychiatric Unit. The study is 10 weeks in duration and employs a crossover design. After a 2 week placebo baseline period, the subjects enter double-blind treatment for 8 weeks, by random assignment receiving either haloperidol for 4 weeks followed by placebo for 4 weeks, or alternatively, placebo for 4 weeks followed by haloperidol for 4 weeks. Dosage, regulated individually, ranges from 0.5 to 10.0 mg/day. To date, of an anticipated 20 subjects, 12 have completed the study. These children, 9 boys and 3 girls, were ages 5.5 to 11.75 years upon study entry. Haloperidol was superior to placebo for reduction of target symptoms with optimal haloperidol dose of 0.5 to 3.5 mg/day (0.02-0.12 mg/kg/day). PMID- 1513923 TI - Pimozide in autistic children. AB - This open pilot study explored the efficacy and safety of pimozide, over a 3-week period, in hospitalized autistic children. Eight males, ages 4.2 to 8.3 years, completed the study. Intellectual functioning ranged from moderate to profound mental retardation. Symptoms included severe withdrawal, stereotypies, hyperactivity and/or hypoactivity, aggressiveness, and temper tantrums. Therapeutic daily doses of pimozide ranged from 3.0 mg to 6.0 mg with a mean of 4.9 mg (0.12-0.32 mg/kg; mean, 0.22). Laboratory studies including electrocardiogram and liver function tests remained within normal limits. Untoward effects were minimal and transient. Decreases of behavioral symptoms were evidenced on all measures including the Children's Psychiatric Rating Scale, Clinical Global Impressions, and Global Clinical Judgments Scale (consensus rating). Of the 5 hypoactive children, 4 showed a decrease in hypoactivity, whereas 1 child showed worsening. These findings are promising and indicate the need for further study. PMID- 1513924 TI - Carbamazepine in hospitalized aggressive conduct disorder children: an open pilot study. AB - Ten subjects completed an open pilot study of carbamazepine in hospitalized aggressive and explosive children diagnosed as having conduct disorder. The subjects (9 boys, 1 girl) ranged in age from 5.25 to 10.92 years (mean = 8.27). Ratings were done at the end of a 1-week baseline period and after 3 weeks of treatment with carbamazepine. Ratings were carried out by multiple raters in several settings, using various rating instruments. The optimal daily doses of carbamazepine ranged from 600 to 800 mg (mean = 630); plasma levels at post treatment rating ranged from 4.8 to 10.4 micrograms/mL (mean = 6.2). Administration of carbamazepine was associated with clinically and statistically significant declines in the target symptoms of aggressiveness and explosiveness. These results are promising and suggest that a critical assessment of the efficacy and safety of carbamazepine is warranted under double-blind and placebo controlled conditions in this population. PMID- 1513925 TI - Profile of a sample of subjects admitted to an acute care psychiatric facility with manic symptoms. AB - A prospective survey was conducted on 155 consecutive subjects with manic symptoms admitted to an inpatient psychiatric facility to identify possible reasons for rehospitalization. Approximately one third were previously hospitalized at the same facility within the past month. Over half (57%) of the sample were admitted because of aggressive episodes. On admission, 80 percent were receiving carbamazepine or lithium for a mood disorder, and 52.3 percent were receiving multiple medications, of which antipsychotics accounted for over half. Forty-four percent of the sample had comorbid substance use on admission, with marijuana and stimulants accounting for the majority of illicit drug use. Medication noncompliance in 64 percent, and identifiable psychosocial stressors in 55 percent, were also likely contributors to rehospitalization. The data highlights specific treatment issues in the care of patients with a manic component to their illness, and suggests the need for individualized discharge planning with careful followup and continual patient education to assist in the transition from inpatient to society. PMID- 1513926 TI - Effects of nitrous oxide on psychological performance. AB - Thirty healthy volunteers took part in this double-blind crossover study comparing 15 percent nitrous oxide in oxygen with 100 percent oxygen. They received each treatment for 45 minutes, in counter-balanced order, with no break between treatments. Central nervous system (CNS) effects of nitrous oxide were assessed by a battery of performance tests and by the Visual Analog Scales. The Digit-symbol Substitution Test showed significant slowing with nitrous oxide as did Symbol-digit Substitution and Sentence Verification. Subjects rated themselves as more drowsy, dizzy, abnormal, drunk, and muzzy on nitrous oxide than on oxygen. Significant carryover effects were seen only for the Alert-Drowsy scale at 2.5 minutes after the start of treatment, and not at any later time point. These results show that the onset and offset of the CNS effects of 15 percent nitrous oxide are sufficiently rapid to permit the study of two treatment periods within a single experimental session. PMID- 1513927 TI - Mechanisms of cocaine-induced sensitization. AB - Rats pretreated with repeated footshock demonstrated an augmentation in cocaine induced locomotor activity and extracellular dopamine concentrations in the nucleus accumbens. Pertussis toxin injections into the A10 region also led to cocaine- induced enhancement in extracellular dopamine levels in the nucleus accumbens and a strong trend towards elevated locomotor activity. Repeated treatment with cocaine led to a blockade of the footshock-induced increase in extracellular dopamine in the medial prefrontal cortex. Prior treatment with pertussis toxin microinjection into the A10 region resulted in enhanced levels of tissue dopamine metabolites in the medial prefrontal cortex following footshock stress. The pertussis toxin- and daily stress-induced behavioral and neurochemical sensitization suggest that behavioral sensitization to these stimuli involves a loss of inhibitory tone on A10 dopamine cells. PMID- 1513928 TI - Biological markers of depression: WHO multi-center studies and future perspective. AB - Dexamethasone suppression test (DST), imipramine platelet binding and sleep EEG in depressed patients were studied by the network of WHO Collaborating Centers. DST and sleep EEG indicated abnormalities characteristic to depression, but imipramine platelet binding failed to show difference between depressed and normal subjects. 20 papers related to markers of depression were presented at the 17th Congress of CINP, Kyoto, 1990. They were introduced under 5 headings: 1) DST and its modifications, 2) serotonergic functions, 3) platelet studies, 4) ocular potentials and melatonin, and 5) brain imaging. There are reviewed here. PMID- 1513929 TI - Rodent models of aggressive behavior and serotonergic drugs. AB - Various models of rodent agonistic behaviour are described, which differentiate between offensive and defensive/flight models. Particular attention is given to one male and one female paradigm for offensive aggression, viz. resident-intruder or territorial (RI) and maternal aggression (MA). After an overview of the serotonin (5-HT) system in the CNS, a description is given of the ligands available. Subsequently the effects of various drugs affecting serotonergic transmission in the RI- and MA-paradigms are described. The 5-HT1A agonists buspirone, ipsapirone and 8-OH-DPAT decreased aggression in RI and MA, but simultaneously led to a marked decrease in social interest and activity, indicative of a non-specific anti-aggressive profile. Non-selective 5-HT1 agonists, such as RU 24969, eltoprazine (DU 28853), and TFMPP reduced aggression quite specific and did not decrease social interest or exploration, but sometimes even increased these behaviours. In RI and MA the behavioural effects of these drugs were roughly similar. In contrast, MA was more sensitive to the treatment with the 5-HT reuptake blocker fluvoxamine, which blocked RI aggression only non specifically at the highest dose. DOI, a 5-HT2 and 5-HT1C agonist, decreased aggressive behaviour and increased inactivity, without affecting social interest and exploration in RI as well as MA. This was, however, accompanied by 'wet dog shaking', characteristic of 5-HT2-receptor stimulation. The non-specific 5-HT agonist (and 5-HT3 antagonist) quipazine also induced 'wet dog shaking' at doses which suppressed aggression, social interest and exploration but increased inactive behaviours (sitting and lying). The discussion attempts to delineate a role for 5-HT receptor subtype involvement in the modulation of aggression, with the restrictions we clearly face with regard to the lack of specific serotonergic agonists and antagonists for certain receptor subtypes. By and large, male and female rats react similarly to treatment with serotonergic drugs stressing the consistent role of 5-HT in different forms of aggression. PMID- 1513930 TI - Variation in evoked potential measures over the menstrual cycle: a pilot study. AB - The P3 component of a visual event related potential (ERP) was studied for five consecutive weeks in six women with normal menstrual cycles. Serum concentrations of luteinizing hormone (LH), estradiol (E2) and progesterone were studied during the same period. Increases in P3 amplitude, although nonsignificant, were noted in the week preceding onset of menses. No significant changes in reaction times to target/nontarget stimuli were noted over the same time period. PMID- 1513931 TI - Endocrine study of the maternity blues. AB - The relationship between several psychological variables and adrenocortical function of the blues is examined in a prospective study of 47 Japanese women. Psychological measures, including the psychiatric interview and assessment of the Schedule for Affective Disorders and Schizophrenia (SASD), the Research Diagnostic Criteria (RDC) and self-rating scales, were administered at the 36th week of pregnancy, on the 3rd or 4th day postnatal and one month after delivery. Twelve subjects (25.5%) were diagnosed as having the blues on the Stein's scale. Women who developed the blues had significantly higher serum bound cortisol than the non-blues group. No significant correlation was obtained between the incidence of the blues and obstetric variables. At one month after delivery, four women (8.5%) were diagnosed as postpartum depression according to the RDC. Our finding that there was no consistent obstetric factor which predisposes women to develop the blues support the hypothesis that hyperadrenocorticalism is important in the genesis of this syndrome. PMID- 1513932 TI - A preliminary study of serotonergic antidepressants in treatment of dysthymia. AB - There is increasing evidence that antidepressants may alleviate symptoms of dysthymia, but few prior studies on selective serotonergic agents. Twenty patients meeting criteria for dysthymia, but not meeting criteria for major depression, received open label trials of a serotonergic antidepressant, either fluoxetine or trazodone. Seventeen (85%) completed three-month medication trials, and of these, twelve (70.6% of completers) responded to treatment. Seven (41.2% of completers) were still in remission on follow-up at five months. Both fluoxetine and trazodone were well tolerated in dysthymics, and showed similar short-term effectiveness in treating dysthymic symptoms. PMID- 1513933 TI - Genetic analyses in neurons and neural crest-derived post mitotic cells. AB - Cationic lipids are shown to be efficient DNA carriers for gene transfer into neurons and chromaffin cells. Chimeric genes containing the coding sequence for the bacterial gene chloramphenicol acetyl transferase (CAT), under various promoter sequences were used to estimate transfection efficiency and to analyse transcriptional mechanisms. Using a ubiquitously expressed construct (RSV-CAT), and an anti-CAT antibody to identify CAT positive cells transfection efficiency was found to be approximately 70% in cultures of hypothalamic neurons. Proenkephalin gene expression was studied in chromaffin cells by employing a chimeric gene containing the rat pro-enkephalin promoter fused to the CAT reporter gene. Using this model we show that the transfected gene is inducible by neurotransmitters and second messengers. The contribution of a specific kinase (protein kinase A, PKA) to proenkephalin gene regulation is analysed using this model system, and expression vectors coding for the catalytic subunit of PKA. PMID- 1513934 TI - Reducing the time needed to conduct conditioned place preference testing. AB - The objective of the present experiment was to demonstrate whether four days of twice-a-day conditioned place conditioning produces a preference that is equivalent to that produced by using eight days of once-a-day training. Two doses of the amphetamine-like stimulant drug cathinone (0.2 and 1.6 mg/kg) were selected to demonstrate the effectiveness of twice-a-day (morning-vehicle; afternoon-drug pairings) conditioning. The 0.2 mg/kg dose of cathinone failed to affect the expression of place preference, whereas the 1.6 mg/kg dose produced a significant (p less than 0.002) shift in CPP from baseline when compared to previous measurements. These results demonstrate that twice-a-day pairings over four days effectively shorten the total duration of training without changing the development of place preference produced by once-a-day over eight conditioning day schedule. PMID- 1513935 TI - Effects of disulfiram, phenoxybenzamine and propranolol on the behaviors evoked by apomorphine and amphetamine in adult cats. AB - The aim of this work was to study the role that the noradrenergic system could play in the mechanism of production of the behaviors evoked by parenteral injection of apomorphine and amphetamine in adult cats. Ten cats were injected s.c. with 2 mg/kg of apomorphine and 2.5 mg/kg of amphetamine in separate sessions. The behaviors were recorded, until control conditions were again attained. In a second stage, disulfiram was administered ip., followed by apomorphine and amphetamine in the same doses as cited above. The effects on behaviors produced by disulfiram and those of apomorphine and amphetamine were recorded by three independent observers. Comparisons of the pre- and post disulfiram behavioral results were analyzed with the help of the non-parametric Wilcoxon signed rank test. In another group of ten cats a similar procedure was carried on employing the alpha and beta noradrenergic blocking agents, phenoxybenzamine and propranolol. The noradrenergic blocking drugs, especially disulfiram and phenoxybenzamine produced by themselves a decrease in motility, in alertness and an increase in indifference and inappetence. Apomorphine and amphetamine administered after the blocking drugs showed slight behavioural modifications, reflection most of them the changes produced by the three blocking drugs. It is concluded that probably the nor-adrenergic system could be involved in the hypomotility elicited by amphetamine. NA is not involved in the induction of the other behaviors evoked by apomorphine and amphetamine. PMID- 1513936 TI - [The future of our history]. PMID- 1513938 TI - [Effect of isoflurane on gas exchange and systemic and pulmonary hemodynamics in man during single lung ventilation]. AB - OBJECTIVE: We studied the effect of 1.5% isoflurane end expiratory fraction on arterial oxygenation and on systemic and pulmonary hemodynamics during nonsurgical single lung ventilation. MATERIAL AND METHODS: The study includes 6 patients undergoing surgical thoracotomy. In all cases a double lumen endotracheal tube was inserted and pulmonary ventilation was performed with a FiO2 = 1. Patients were placed on lateral decubitus position. The following variables were measured: mean arterial pressure (MAP), mean pulmonary artery pressure (MPAP), central venous pressure (CVP), capillary pulmonary pressure (CPP), cardiac output (CO), and Qs/Qt. Measurements were taken at three different situations. The first was done under bilateral pulmonary ventilation and intravenous anesthesia with thiopental, fentanyl, and diazepam. The nondependent lung was collapsed by means of a selective ventilation of the dependent lung, and the second series of measurements was done 20 min after intravenous anesthesia. The third block of data was obtained after 15 min of respiratory ventilation with 1.5% isoflurane. RESULTS: Single lung ventilation induced a significant decrease of Pa O2 (379 +/- 96 mmHg vs 208 +/- 93 mmHg) and a significant increase in Qs/Qt (20 +/- 8% vs 30 +/- 10%). However, during isoflurane ventilation there were no significant changes in PaO2 (208 +/- 93 mmHg vs 204 +/- 94 mmHg) nor in Qs/Qt (30 +/- 10 vs 28 +/- 8). Isoflurane elicited a significant decrease of the CO, whereas MPAP, RVS, and PvO2 did not show significant variations. CONCLUSIONS: We conclude that 1.5% isoflurane end expiratory concentrations did not significantly affect pulmonary oxygenation during single lung ventilation. PMID- 1513937 TI - [Application of high frequency jet ventilation during microsurgery of the larynx under suspending laryngoscopy]. AB - OBJECTIVES: This study describes the results obtained with high frequency jet ventilation (HFJV) in 19 patients who underwent laryngeal microsurgery under suspending laryngoscopy. MATERIAL AND METHODS: After premedication and anesthetic induction with propofol (Diprivan R, ICI-Farma), we performed an endotracheal intubation (28F tube) under succinyl-choline facilitation. Conventional ventilation was started at a rate of 14-16 cpm with a minute volume of 8-10 l, and a FiO2 of 0.4 (air-oxygen). The endotracheal tube was replaced by an insufflation catheter of 2 mm internal diameter and HFJV was initiated at a rate of 100 cpm, inspiratory time equal to the 33% of the total cycle, generator pressure of 2.5-3.6 kg/cm2, and similar FiO2. We used an Ergojet CVT (Temel SA) respirator that allowed continuous monitoring of the injector released volume during each cycle (Vjet) as well as the air way pressure. Anesthesia was maintained with continuous propofol perfusion. RESULTS: During HFJV there were no significant hemodynamic alterations and surgeons considered that the condition of the surgical field was excellent. Air way pressure was maintained at low levels in all cases, although brief hypertensive episodes occurred during laryngeal manipulation. Oxygenation was satisfactory in all except one patient with chronic obstructive pulmonary disease. Conventional ventilation and HFJV did not induce significant differences in alveolar ventilation nor in PaCO2. However, during HFJV oxygenation and ventilatory levels suffered a high degree of interindividual variability. This phenomenon could be due to the existence of variable degrees of gas reflux during insufflation. CONCLUSIONS: We conclude that HFJV is a very useful technique for anesthesia in laryngeal microsurgery. However, an appropriate monitoring of ventilatory dynamics and a detailed knowledge of the influences of patient's characteristics on HFJV are required. PMID- 1513939 TI - [Incidence of headache following intradural anesthesia with 26 gauge needles depending on whether the punction is done with the bevel perpendicular or parallel to the dura mater fibers]. AB - OBJECTIVES: To determine the incidence of headache after lumbar puncture, we prospectively studied 270 patients who underwent intradural anesthesia for programmed urologic, traumatologic, general, and gynaecologic surgery. PATIENTS AND METHODS: The mean age of the patients was 55.6 +/- 16.9 years. There were significant differences between the age of women (54.8 +/- 15.5 years) and men (56.4 +/- 18.4 years). Intradural anesthesia was performed with a Becton Dickinson 26G needle with a Quincke tip. Patients were randomly divided into two groups according to that puncture was directed parallel (group 1) or perpendicular (group 2) to the dura-mater fibers. When the spinal liquid dripped through the needle, 2 ml of a 0.75% (15 mg) solution of bupivacaine and 0.2 ml of a 50% (100 mg) solution of glucose were injected. No special measures were undertaken during the postoperative phase. The incidence of headache was analyzed 72 hours after puncture. RESULTS: One patient of group 1 (0.66%) and 6 patients of group 2 (5%) presented headache. This difference was not statistically significant. Differences between the incidence of headache in women (4.05%) and in men (2.15%) were also not significant. PMID- 1513940 TI - [Continuous intradural anesthesia in geriatric patients undergoing orthopedic and traumatologic surgery]. AB - OBJECTIVES: The aim of the study was to prospectively evaluate the results of continuous intradural anesthesia with 18G Tuohy needle and 20G catheter in geriatric patients. MATERIAL AND METHODS: We studied 70 patients with a mean age of 75.9 +/- 10.8 years who were subjected to orthopedic or traumatologic surgery of the lower extremities with a duration of 104.6 +/- 53.6 min. RESULTS: Success index was 95.7%. The initial dose of 1% tetracaine was 10.36 +/- 3.96 mg, the second dose in 29 patients was 7.2 +/- 2.7 mg, the third in 7 cases was 7.40 +/- 2.47 mg, and the total dose was 14.56 +/- 5.6 mg. The metameric level was between T8 and T11 in 80.32% of patients. Peroperative complications were limited to paresthesia in 5 cases (7.14%) during insertion of the catheter, difficulties in catheter placement in one case (1.42%), and accidental catheter extraction during withdrawal of the needle in 2 cases (2.85%). Ten patients (14.28%) presented arterial hypotension (pressure decrease greater than 30% of baseline systolic arterial pressure). During the postoperative phase there were 3 cases of slight headache after dural puncture (4.28%) that recovered with conservative treatment, and one case of lumbalgia at the puncture zone (1.42%). CONCLUSIONS: Continuous intradural anesthesia with the material used in this study is technically easy. It allows to accurately reach the desired metameric level, avoiding massive sympathetic blockade, and providing a steady hemodynamic condition. All these effects are essential for anesthesia in geriatric patients. PMID- 1513941 TI - [Patient-controlled analgesia (PCA) with variable doses: an alternative to conventional PCA?]. AB - We have prospectively studied the effects of three types of patient controlled anesthesia (PCA) in 30 patients who underwent elective upper abdominal surgery. Patients were allocated into three groups of 10. The first group received postoperative anesthesia by means of intravenous conventional PCA at fixed demand doses (PCADF). A second group was treated with demand doses that were varied in each bolus according to the intensity of pain (PCADV). A third group received continuous infusion with additional demand doses in variable bolus (PCAC + DV). The analgesic agent used in this study was morphine chloride. The total accumulated doses of morphine in PCADV group were lower than those of the other two groups. These differences were statistically significant when they were compared with PCADF group (p less than 0.01 at 2 and 6 hours; p less than 0.05 at 12 and 24 hours) and with PCAC + DV group (p less than 0.01 at 2, 6, 12, and 24 hours). Differences in morphine consumption during the different time intervals were markedly significant between 0 and 2 hours after the onset of PCA. PCADV required lower doses (p less than 0.01). After the first 2 hours, patients of PCADV group continued using lower morphine doses, but these differences were not significant when compared with PCADF group, although were present with respect to patients of PCAC + DV group (p less than 0.01). The incidence of secondary effects was not significantly different among the three groups. Based on these results we propose a modification in present PCA pumps. PMID- 1513942 TI - [The morphine-scopolamine combination in chloroform anesthesia]. AB - After introduction of surgical anesthesia with general agents such as ether and chloroform, a large number of deaths due to anesthetic toxicity were reported. With the aim to reduce toxicity several types of mixtures were devised. One of the most important was the association of opioids and scopolamine. This technique was compiled in a thesis on the use of morphine and scopolamine during anesthesia with chloroform which was presented by Dr. Jose Blasco Reta at the University of Madrid the 27th of June of 1907. Claude Bernard was the first to use this technique. He was based on the assumption that a previous injection of 1 cg of morphine acetate will decrease both, the needs and the risk of chloroform since this procedure shortened the excitation period, decreased ether-induced bronchial congestion, and prolonged for several hours the analgesic effect in the postoperative phase. The first who applied this technique in Spain was Dr. Losada, and Dr. Emilio Ruiz observed the rapid action of the mixture. After 1900, Schneiderlein added scopolamine in order to decrease the excitation and to reduce vomiting secondary to the association morphine-chloroform. Scopolamine was administered in 2 or 3 injections. Jun our country Dr. Lozano Monzon and Dr. Recasens used this pharmacologic association and considered it of beneficial effects when applied during labour. In a total number of 4,240 anesthetic procedures using the same technique, Dr. Blasco Reta reported 24 deaths, among them the first that occurred to Mr. Victor Escribano between 1902 and 1903. Mortality was considered to be 1/1,000 cases. PMID- 1513943 TI - [Experience with 100 anesthetized patients ventilated with laryngeal mask]. AB - We studied 100 adult patients who were anesthetized for different surgical procedures and were ventilated with laryngeal mask either with spontaneous or controlled ventilation. Despite of the inexperience we achieved an appropriate placement of the mask in 99% of cases; 74% at the first attempt, 22% at the second, and 4% at the third. In 87.8% of patients we had an adequate control of the air way. In 12.2% of cases there were problems in relation to the controlled ventilation. In one patient we were unable to correctly place the mask and another anesthetic technique had to be performed. Laryngeal mask is useful in the control of the air way in anesthetized patients with spontaneous ventilation. Some inconvenience may arise when controlled ventilation is used. PMID- 1513944 TI - [Paradoxical bradycardia and hemorrhagic shock]. AB - We report two cases of paradoxical bradycardia associated with acute hemorrhage and hypotension in conscious patients who had no antecedents of myocardial disease. In some cases of massive and rapid hypovolemia the occurrence of bradycardia may constitute a protective reflex directed to improve ventricular filling. This reflex is probably mediated by a vagal mechanism which acts on a previously increased sympathetic nerve tone and tends to maintain systemic vascular resistances and keep a cerebral blood flow high enough to preserve conscience level. We discuss the differential diagnosis with vasovagal syncope which can also occur during the initial phases of acute hemorrhage and during the preterminal bradycardia that develops during the so called "irreversible phase" of shock. Paradoxical bradycardia during hemorrhagic shock is always a sign of important bleeding that requires a rapid reposition of volemia. Administration of vagolytic agents is contraindicated since they can favour the occurrence of severe cardiac arrhythmias. PMID- 1513945 TI - [Prevention of pulmonary embolism in the operated patient]. PMID- 1513946 TI - [Transitional cutaneous hyperesthesia following block of the ilioinguinal and iliohypogastric nerves]. PMID- 1513947 TI - [Anesthesia with propofol in a case of hypertension and hyperthyroidism]. PMID- 1513948 TI - [Respiratory depression following anesthesia with alfentanyl]. PMID- 1513949 TI - [Cardiac herniation following pneumonectomy]. PMID- 1513950 TI - [Diagnosis of left bronchoesophageal fistula during esophagectomy with right thoracotomy]. PMID- 1513951 TI - [Hypovolemic shock and hip arthroplasty]. PMID- 1513952 TI - The 1991 C. H. McCloy Research Lecture: unraveling the mystery of the response complexity effect in skilled movements. PMID- 1513953 TI - Choice of exercise: a predictor of behavioral risks? AB - After controlling for differences in gender, educational achievement, and exercise duration among a sample of 7,248 Americans 18-34 years old, we found that runners-joggers-fast walkers (RJWs) and tennis players were less likely to be obese, smoke, consume large quantities of alcohol, and drive without seat belts than those who participate in team and an aggregate of other sports. These behavioral differences might be explained by imprecise data, intervening variables such as exercise intensity, or other variables that were not measured. But a more interesting explanation is that running-jogging-fast walking and playing tennis are integral components of healthy lifestyles, and team sports and some other exercise behaviors are part of riskier ways of living. No consistent association was found between duration of exercise and behavioral risk. PMID- 1513954 TI - Physical activity levels of 5-11-year-old children in England as determined by continuous observation. AB - Continuous observation of the physical activity of 56 preadolescent children was conducted in four regions of England from October 1988 to July 1989. Observations were undertaken during school break times, lunch times, and physical education lessons, as well as during the children's free time. Of total time observed, the children spent 32.4% of it engaged in moderate to vigorous physical activity (MVPA). Children were shown to be most active during school breaks and least active during free time at home. However, it is thought that cardiorespiratory benefits are best achieved by participation in sustained periods of MVPA. Only 8 (14%) of the 56 children were observed to participate in MVPA for sustained periods of 20 min or longer. A random sample of 55 physical education lessons was observed. Only 6 children engaged in MVPA for sustained periods of 5 min or more, and no children participated in MVPA for 10 min or longer. The implications of these results are that, although the children engaged in a reasonable amount of MVPA, it may not have been sustained for periods of sufficient length to produce a cardiovascular training response. Consideration is given to ways of promoting lifelong involvement in physical activity. PMID- 1513955 TI - The rise and demise of Harvard's B.S. Program in Anatomy, Physiology, and Physical Training: a case of conflicts of interest and scarce resources. PMID- 1513956 TI - Transition play in team performance of volleyball: a log-linear analysis. AB - The purpose of this study was to develop and test a method to analyze and evaluate sequential skill performances in a team sport. An on-line computerized system was developed to record and summarize the sequential skill performances in volleyball. Seventy-two sample games from the third Federation of International Volleyball Cup men's competition were videotaped and grouped into two categories according to the final team standing and game outcome. Log-linear procedures were used to investigate the nature and degree of the relationship in the first-order (pass-to-set, set-to-spike) and second-order (pass-to-spike) transition plays. Results showed that there was a significant dependency in both the first-order and second-order transition plays, indicating that the outcome of a skill performance is highly influenced by the quality of a preceding skill performance. In addition, the pattern of the transition plays was stable and consistent, regardless of the classification status: Game Outcome, Team Standing, or Transition Process. The methodology and subsequent results provide valuable aids for a thorough understanding of the characteristics of transition plays in volleyball. In addition, the concept of sequential performance analysis may serve as an example for sport scientists in investigating probabilistic patterns of motor performance. PMID- 1513957 TI - The reliability of distance run tests for children in grades K-4. AB - The purpose of this study was to determine test-retest reliability for the 1 mile, 3/4-mile, and 1/2-mile distance run/alk tests for children in Grades K-4. Fifty-one intact physical education classes were randomly assigned to one of the three distance run conditions. A total of 1,229 (621 boys, 608 girls) completed the test-retests in the fall (October), with 1,050 of these students (543 boys, 507 girls) repeating the tests in the spring (May). Results indicated that the 1 mile run/walk distance, as recommended for young children in most national test batteries, has acceptable intraclass reliability (.83 less than R less than .90) for both boys and girls in Grades 3 and 4, has minimal (fall) to acceptable (spring) reliability for Grade 2 students (.70 less than R less than .83), but is not reliable for children in Grades K and 1 (.34 less than R less than .56). The 1/2 mile was the only distance meeting minimal reliability standards for boys and girls in Grades K and 1 (.73 less than R less than .82). Results also indicated that reliability estimates remained fairly stable across gender and age groups from the fall to spring testing periods, with the exception of the noticeably improved values for Grade 2 students on the 1-mile run/walk test. Criterion referenced reliability (P, percent agreement) was also estimated relative to Physical Best and Fitnessgram run/walk standards. Reliability coefficients for all age group standards were acceptable to high (.70 less than P less than .95), except for Fitnessgram standards for 5-year-old girls on the 1-mile test for both fall and spring and for 6-year-old boys and girls on the 1-mile test administered in the spring. PMID- 1513958 TI - The difficulty of sit-ups tests: an empirical investigation. AB - This study estimated the difficulty of various sit-ups tests using an item response theory (IRT) model, the Rasch Poisson Counts model. Scores were obtained on 18 sit-ups tests. All tests were thought to vary in difficulty based on clinical observations. Item difficulty was defined by the Poisson model as the difficulty of Step 1, where the difficulty of a step represented the difficulty of completing a sit-up. The difficulty values of the tests ranged from -4.02 to 3.57. The easiest test was executed with hands on thighs and feet anchored. Most tests had good fit values. The results demonstrated that a variety of sit-ups tests can provide a range of difficulties and variety in forming a sit-ups test bank. PMID- 1513959 TI - EMG amplitude and spatial assimilation effects in rapid bimanual movement. AB - To investigate whether spatial assimilation effects are due to premovement control processes or postinitiation feedback processes, surface EMG recordings were made from two agonists and one antagonist during both single and dual movements involving the upper limb(s). In the single condition, subjects (N = 7) made 25 Short (20 degrees) and 25 Long (60 degrees) reversal movements using levers in the sagittal plane, in 195 ms to reversal. In the dual condition, both Short and Long movements were performed simultaneously for 75 trials, the last 25 of which were without knowledge of results. Subjects overshot the Short target in the dual condition, showing spatial assimilation effects. Overshooting was associated with increased peak EMG in the initial (premovement) agonist burst, supporting the notion that spatial assimilation effects are modulated via premovement control processes. PMID- 1513960 TI - "Show and tell" in the gymnasium revisited: developmental differences in modeling and verbal rehearsal effects on motor skill learning and performance. AB - Little research has investigated the observational learning process from a developmental perspective. The purpose of this study was to extend previous research by considering two factors: performance versus learning and sequencing versus form scores. Children (N = 60) comprising two age groups (5-0 to 6-11 and 8-0 to 9-11 years) were randomly assigned to verbal rehearsal only, model only, or model plus verbal rehearsal conditions. The task was a 6-part motor skill sequence in which proper sequencing and quality of form were assessed. A 2 x 3 x 4 (age group by model type by trial blocks) repeated measures MANOVA revealed a significant three-way interaction. Older children performed equally well under any of the model type conditions during both performance and learning. For younger children, a model plus rehearsal was superior to rehearsal only on sequence and form at performance and learning and superior to model only on sequence scores during the first two performance trial blocks. Model only and model plus rehearsal conditions were equally effective on form scores. These results suggest that age differences exist in the modeling of motor skills under conditions varying in model type, sequence and form scores, and performance and learning phases. PMID- 1513961 TI - Muscular strength and endurance as a function of age and activity level. AB - Muscular strength, endurance, and rate of fatigue were studied in populations of various ages actively engaged in strength and endurance training, as compared with those not engaged in such activities. The strength and fatigability of the elbow flexor muscles were studied for 62 subjects at the ages of 20 (n = 11 active, 10 inactive), 35 (n = 11 active, 10 inactive), and 50 (n = 10 active, 10 inactive) years, tested within 2 years of the appropriate age. They performed a 6 min bout of maximal rhythmic contractions of the dominant arm at a rate of 30 contractions per min. Force applied to the transducer was converted into electrical activity and transmitted to a recorder, where differences in mean values for initial strength, final strength, absolute endurance, and relative endurance were examined for significance. Rates of fatigue and the fatigue curves were also obtained for each group. Results revealed significantly less muscular strength, absolute endurance, and relative endurance as the age of the subjects increased, but no significant difference for age was found in final strength at the conclusion of the exercise bout. Significant differences were found between active and inactive subjects in initial strength, final strength, and absolute endurance in favor of the active subjects. No significant interaction between activity level and age was found for any of the dependent variables. The rates of fatigue were similar for all ages except for the inactive 20-year-old subjects, whose rate of fatigue was markedly slower than that found for all other groups of subjects.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1513962 TI - The effects of cold application and modified PNF stretching techniques on hip joint flexibility in college males. AB - The purpose of the study was to determine the effects of modified Proprioceptive Neuromuscular Facilitation (PNF) flexibility techniques on hip flexion in college males and to determine if local cold application enhances the effectiveness of these techniques. Male subjects (N = 120), with an average age of 21.5 +/- 2.7 years, were randomly assigned to one of four different kinds of stretching treatments with cold or no cold application (15 per group). Range of motion (ROM) in degrees was determined following four stretching techniques: three modified PNF (PCP, 3-PIECP, 3-PIFCP) and a passive stretch (P). Data were analyzed using a 2 (conditions) x 4 (treatments) ANOVA. There were no significant differences in ROM between cold and no cold conditions. Significant differences existed among ROM techniques (p less than .05). Post hoc analyses revealed that the three modified PNF techniques resulted in greater ROM than the passive stretch technique. However, we conclude that cold application does not influence the effectiveness of selected stretching techniques. PMID- 1513963 TI - Effect of including parents in a school-based exercise and nutrition program for children. AB - The purpose of this study was to examine the effect of parental involvement in a school-based program about exercise and nutrition. One fifth grade and one sixth grade class were randomly assigned to each of the three different treatment conditions, a school-and-home condition (n = 45), a school-only condition (n = 43), and a control condition (n = 44). In the school-and-home condition, the children's parents were also asked to participate in nutritional and exercise activities at home as a family "home team." A multivariate analysis of variance on change scores was completed on the following variables: height, weight, skinfold, sit-and-reach, sit-ups, mile run, exercise knowledge, saturated fat, cholesterol, percent calories from fat, percent calories from carbohydrates, and nutrition knowledge. There was a significant difference among groups. The school and-home and school-only groups showed significantly greater improvement than the control group but were not significantly different from each other. Univariate analyses on posttest scores indicated that the school-and-home children scored significantly higher than the control group on sit-and-reach flexibility and nutrition knowledge. The results indicate that including the family was primarily effective in facilitating children's improvements in flexibility and nutrition knowledge rather than in diet and exercise behaviors. PMID- 1513964 TI - Validation of the Rockport Fitness Walking Test in females 65 years and older. PMID- 1513965 TI - The acquisition and retention of a timing task: effects of summary KR and movement time. PMID- 1513966 TI - Comment on accuracy of references in Research Quarterly for Exercise and Sport (Stull, Christina, and Quinn, 1991). PMID- 1513967 TI - Benefit from long-term O2 therapy in chronic obstructive pulmonary disease patients. AB - The Nocturnal Oxygen Therapy Trial (NOTT) and Medical Research Council (MRC) trial have clearly indicated that long-term oxygen therapy (LTO) improved survival in patients with hypoxemic chronic obstructive pulmonary disease (COPD), but the mechanisms accounting for this improved survival could not be established. In particular, there was no link between survival and changes in pulmonary hemodynamics. More recent studies have shown even better results of survival in patients under LTO after at least 5 years. LTO improves the quality of life in these patients by improving their neuropsychological condition, by increasing their walking distance, and by reducing the time spent in hospital. Whether LTO improves pulmonary hemodynamics and right ventricular function is still debated. No significant changes in mean pulmonary artery pressure (PAP) were observed in the MRC study in patients receiving O2 during greater than 15 h/day, whereas a modest but significant fall in PAP was noticed after 6 months in the NOTT patients receiving O2 during greater than 18 h/day. In our own study, confirmed by more recent data from our laboratory, a reversal in the progression of pulmonary hypertension was observed in patients receiving O2 during greater than 16 h/day, but it is not possible to say whether a rather small decrease in PAP and pulmonary vascular resistance will have favorable effects on life expectancy. Presently, we do not know whether LTO can reverse, at least partially, the structural changes in the pulmonary vessels possibly induced by chronic alveolar hypoxia, and we need to perform further studies in this field. PMID- 1513968 TI - Exercise-limiting factors in respiratory distress. AB - Exercise performance data, circulatory function and respiratory and leg muscle quality, expressed as muscle fiber composition, are reviewed and together with our own data discussed as possible limiting factors for physical performance in chronic obstructive pulmonary disease (COPD). COPD is regarded as synonymous with reduced physical performance, exaggerated breathlessness or dyspnea, muscle hypotrophy and/or wasting and, frequently, malnutrition. Impaired right ventricular circulatory function seems to be essential. The observed preponderance of fast twitch (FT), 'glycogenolytic' and capillary-poor muscle fiber type in the investigated muscles might reflect endowment, a 'hypoxic vasoconstriction'-related downregulation of the other main fiber type: the slow twitch (ST), capillary-rich, fatigue-resistant fiber, and/or selective muscle trauma to ST fibers. Ischemic heart disease (IHD) patients demonstrate a similar fiber type pattern in leg muscles. Both COPD and IHD patients have low leg muscle and plasma deposits of antioxidants such as coenzyme Q10 (CoQ10) and alpha tocopherol. This could reflect a depressed resistance to radical induced cell trauma and/or malnutrition. The magnitude of the antioxidant reduction is less pronounced in patients rich in FT fibers indicating a ST fiber-related susceptibility to trauma. Treatment of other muscle disorders including heart muscle with, e.g., CoQ10 improves performance due to a causative enhanced antioxidant potential, reduced catabolism and/or an upregulated muscle anabolism, increased mitochondrial volume/function, etc. Such data are lacking in COPD. PMID- 1513969 TI - Muscle energetics and ultrastructure in chronic hypoxia. AB - High-altitude exposure impairs both maximal aerobic and anaerobic (lactic and alactic) performances. The maximal aerobic power (VO2max) decreases exponentially with increasing altitude. At 5,350 m, a sudden rise in inspired O2 pressure (PIO2) was found to raise the VO2max of acclimatized lowlanders from 70 to only 92% of the control sea-level value. Since the hemoglobin concentration was about 35% higher than that of the controls, hemoglobin O2 saturation was restored to about 100%, and maximal cardiac output was only 10-20% lower than at sea level, the above result can only be the consequence: (1) of a reduced muscle mass and/or of muscle deterioration, and (2) of impaired muscle perfusion. In muscle biopsies taken from the vastus lateralis muscles of mountaineers after a 6- to 8-week sojourn at high altitude, a reduction in the fiber cross-sectional area was found which was accompanied by a decrease in the volume density of the mitochondria and by a lower tissue oxidative capacity. In acclimatized lowlanders, the maximal blood lactate concentration after exhausting exercise was halved compared to sea level conditions. On the other hand, the peak anaerobic power was not affected by severe hypoxia within the first 3 weeks of exposure; thereafter, it decreased by about 25%, probably as a consequence of muscle deterioration. It is concluded that, whereas in acute hypoxia VO2max is primarily reduced by a lack of O2, in chronic hypoxia muscle deterioration may become an important factor contributing to the limitation of the maximal aerobic performance. PMID- 1513970 TI - Can long-term oxygen therapy improve exercise capacity and prognosis? AB - The lack of studies as to whether the correction of desaturations during exercise can play a role in improving survival still leaves many problems usually met in the common practice open. (1) Why prescribe long-term oxygen therapy (LTOT) on exercise? Up to now, supplemental oxygen during exercise seems more an approach to the 'dyspnea symptom' than a pivotal component of a comprehensive strategy for long-term management of severe chronic airway obstruction. (2) Who needs LTOT on exercise? It seems reasonable to correct desaturations if this leads to a substantial improvement in exercise tolerance. As to the method of clinical assessment, pulse oximetry can be used for measuring desaturation between rest and exercise, although absolute values are not reliable. (3) How to prescribe LTOT on exercise? In practice, the O2 flow able to prevent desaturation on exercise, restoring an SaO2 greater than 90%, is the usual prescription criterion after an appropriate testing able to demonstrate a significant increase in exercise tolerance and conducted comparing the results breathing air with those on O2, the patient being unaware of the inhaled mixture. (4) How to administrate LTOT on exercise? A portable source is usually employed to allow the greatest possible independency. A reservoir nasal cannula can halve the oxygen wastage and is less expensive than a pulse demand valve. In patients needing 24-hour oxygen therapy the transtracheal catheter is being used more and more at present.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1513971 TI - Is loss of body weight in chronic obstructive pulmonary disease patients with emphysema secondary to low tissue oxygenation? AB - The available clinical information to date does not support the hypothesis that tissue oxygen debt is the primary cause of the wasting process in the chronic obstructive pulmonary disease (COPD) patient population. However, this should not deter the 'believers' of the hypothesis from further investigation. The information outlined above supports the need for reconsideration of this clinical problem. Tissue oxygen requirements and utilization is a complex interplay of multiple variables. Likewise, the assessment of nutritional status in the setting of oxygen therapy is complicated by shifts in body fluid compartments independent of changes in the fat-free mass (FFM). Utilization of newer techniques will be required to resolve the contribution of low tissue oxygenation to the wasting process. The continued development of noninvasive methods for the assessment of tissue metabolism, cardiac function, and tissue energy requirements will allow investigators to further clarify the relationship between tissue oxygenation and metabolism in patients with COPD. Clinical trials designed to examine this issue must recognize the multiple effects of oxygen on all aspects of nutrient utilization, including caloric intake, needs, and tissue delivery. Failure to address all aspects of this system will lead to continued debate regarding the etiology of weight loss in the COPD patient population. PMID- 1513972 TI - Effects of long-term oxygen therapy due to portable liquid oxygen tanks in disabled malnourished chronic obstructive pulmonary disease patients with borderline hypoxemia. Aim of the study and methods. AB - Long-term oxygen therapy by light-weight portable liquid oxygen systems may improve the degree of functional handicap in patients with severe chronic obstructive pulmonary disease (COPD), borderline hypoxemia or exertional hypoxemia, limited walking distance and malnutrition who do not fulfill the Nocturnal Oxygen Therapy Trial criteria for long-term oxygen therapy. The paper will discuss a proposal for a study plan to test this hypothesis. After a period of stabilization, the methods of measurements include functional tests (walking tests, cycle exercise test [FiO2 21, 35%], baseline measurements of pulmonary function, arterial blood gases, lactate, right heart catheterization, radionuclide ventriculography). The study is designed as a multicentric, controlled, parallel and randomized test for oxygen treatment and no treatment by oxygen. The main outcome will be tested on the results of functional tests (walking tests, VO2max) to demonstrate the possible benefit of long-term oxygen therapy in borderline hypoxemic COPD patients. PMID- 1513973 TI - Predictors of survival in patients treated with long-term oxygen therapy. AB - Long-term oxygen therapy (LTOT) has been shown in two controlled trials to improve survival in patients with hypoxic chronic obstructive pulmonary disease. The cause of this improved survival is unknown and was best correlated in the Medical Research Council (MRC) trial with the sum of the PaCO2 and the red cell mass. However, the survival curves of treated and untreated patients in the MRC trial for males were not significant until greater than 500 days of treatment. This suggests that some patients derive little benefit from LTOT. Follow-up data from the National Institutes of Health (NIH) trial indicate that pulmonary haemodynamics, including pulmonary vascular resistance, predict survival in such patients. In a previous study in 115 randomly selected patients with chronic obstructive pulmonary disease (COPD) who were not treated with LTOT, we found that PaO2 and PaCO2, measured when breathing air, were more significant predictors of survival than the presence of cor pulmonale or right ventricular function. We have also compared a group of 154 patients treated with LTOT in two centres, in Warsaw and Edinburgh, where criteria for patient selection for LTOT and subsequent survival curves were very similar in both centres. A pulmonary arterial pressure of greater than 29 mm Hg and a PaO2 when breathing air of less than 7.0 kPa produced a significant decrease in survival using a Cox survival model. These results suggest that patients with more severe COPD may not benefit from LTOT. Other factors such as poor compliance with treatment, lack of adequate oxygenation and increasing age of patients prescribed LTOT may also contribute to the reduced benefit from this treatment.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1513974 TI - Indications for long-term oxygen therapy. AB - The Medical Research Council and the Nocturnal Oxygen Therapy Trial studies clearly demonstrated that long-term oxygen therapy (LTOT) for more than 15 h/day improved mortality and morbidity in a well-defined group of patients with chronic obstructive pulmonary disease. There are no similar randomised control studies in patients with other hypoxaemic lung diseases such as pulmonary fibrosis and pneumoconiosis. The prescription of oxygen for other restrictive lung disorders is complicated by hypoventilation requiring mechanical support as well as oxygen and should be restricted to special centres. The clearest indications for LTOT are for patients with cor pulmonale, hypoxic chronic bronchitis and emphysema, and in terminally ill patients who require palliation. Before LTOT is considered, the patient must be clinically stable and on appropriate optimum therapy such as antibiotics, bronchodilators, physiotherapy and having stopped smoking tobacco. Many patients first present for LTOT with profound hypoxaemia and hypercapnia during an infective, often oedematous exacerbation of their lung disease. Assessments should occur during convalescence when the patient is clinically stable. They should be shown to have a PaO2 less than 7.3 kPa and/or a PaCO2 greater than 6 kPa on two occasions at least 3 weeks apart. FEV1 should be less than 1.5 litres, and there should be a less than 15% improvement in FEV1 after bronchodilators. All patients should be assessed by an experienced chest physician. Patients with a PaO2 between 7.3 and 8 kPa who have polycythaemia, right heart failure or pulmonary hypertension may gain benefit from LTOT but this is still to be clearly proven.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1513975 TI - [Hygiene care--will it become a luxury?]. PMID- 1513977 TI - [Care rich in relationships]. PMID- 1513976 TI - [To take action before the first time]. PMID- 1513978 TI - [In the heart of disadvantaged cities. Interview by Estelle Poirson]. PMID- 1513979 TI - [High school: they look drugs in the face]. PMID- 1513980 TI - [New materials in anesthesia]. PMID- 1513981 TI - [Education in relationships, myth or reality?]. PMID- 1513982 TI - [A database for nursing service]. PMID- 1513983 TI - [Lumbar puncture in pediatrics]. PMID- 1513984 TI - [A consensus, otherwise nothing!]. PMID- 1513985 TI - [Marc Livet: "psychiatry does not know how to sell itself". Interview by Veronique Blocquaux]. PMID- 1513986 TI - [Moulins school: psychiatry takes its mark]. PMID- 1513987 TI - [Listening is good medicine. Interview by Claire Manicot]. PMID- 1513988 TI - [The nurse, the baker and a little liter]. PMID- 1513989 TI - [The rediscovery of the corporal scheme]. PMID- 1513990 TI - [Sophrology, why not in cardiology?]. PMID- 1513991 TI - [Towards a unified and unique profession]. PMID- 1513992 TI - [Sexually transmitted diseases]. PMID- 1513993 TI - [AIDS: free screening]. PMID- 1513994 TI - [Division of tasks between nurses and nurses aides]. PMID- 1513995 TI - [Work contract]. PMID- 1513996 TI - [Solar protection]. PMID- 1513997 TI - [Parasitic diarrhea in children]. PMID- 1513998 TI - [Passive smoking in children]. PMID- 1513999 TI - [Touch and music in neonatology or the maintenance of the parent-child bond]. PMID- 1514000 TI - [Stress management]. PMID- 1514001 TI - [Allergy to molds]. PMID- 1514002 TI - [Severe allergy to sesame]. PMID- 1514003 TI - [Prevention of falls in the aged subject]. PMID- 1514004 TI - [Falls in the aged subject--a public health problem]. PMID- 1514005 TI - [Epidemics of salmonellosis in the geriatric mileiu]. PMID- 1514006 TI - [Sleeping disorders in the aged subject]. PMID- 1514007 TI - [Nutrition and eating pleasure in the third age]. PMID- 1514008 TI - [Melodic Intonation Therapy]. PMID- 1514009 TI - [Natural methods of contraception]. PMID- 1514010 TI - [Chronic urticaria. Characteristics, diagnosis and treatment]. AB - Urticaria and angioedema are skins disorders more frequently in allergy sections of clinics. They are a serious health problem because in 90% of the cases, the causes are not determined and in a similar percentage, the results of treatment are not satisfactory either to the patient or the consulting physician. To find out some characteristics of chronic urticaria in our area, we studied 45 patients who sought consultation at the General Regional and Zone Hospital No. 6 of the IMSS in Ciudad Madero, Tamps., in a given time span. Persons of both sexes and all ages were included. All were given a complete allergy medical history and a complete series of laboratory exams to try to determine the diagnosis. Etiology the treatment was done separating the patients into two groups with four types of antihistaminics considered within the basic medicinal chart of the IMSS. The study shows that the skin rash and angioedema together had a frequency rate of 81.25% with a greater frequency in females (81.25%) between the ages of 20 and 40. The etiology could be determined in only 37.77% of the cases with a high emphasis on parasite. It is notable that in 56.25% of the cases there was an earlier history of some type of respiratory allergy not diagnosed. We observed that there were better results if two antihistamines H1 were combined to provide specific treatment of immunotherapy with good results. PMID- 1514011 TI - [Epidemiology of allergic diseases in the Tampico-Ciudad Madero- Altamira metropolitan area]. AB - There is a need to know the epidemiology behavior of health problem, with the purpose of creating the supporting basis for all action to its concern. In the cities Tampico, Madero and Altamira, a systematic exploration of the prevalent situation of allergic disorders did not exist: now, there is a study of 730 people selected at random, by means of questionnaire including 55 items applied to the population as a whole that live in the different zones of this area. It has been found that 54% show an allergic illness, it must be observed that in 66% of them a familial allergic history existed, whereas 45% has seasoning crisis environmental-related. PMID- 1514012 TI - [Allergenic flora in the Valle de Mexico. Relation to food sensitization of vegetable origin (5)]. PMID- 1514013 TI - [Skin reactivity in allergic conjunctivitis]. AB - Allergic conjunctivitis is a very common disease in our country. We intend to determine the most frequent ocular involvement and the specific sensitivity to common aeroallergens. A longitudinal prospective study was performed on 20 patients from the allergy/immunology and ophthalmology outpatient service, Hospital Infantil de Mexico Federico Gomez, from May to July 1990. All of them had allergic conjunctivitis and were evaluated for ocular involvement and reactivity to common aeroallergens by skin prick test. PMID- 1514014 TI - Immunoassay for the determination of surfactant apoprotein (SP-A) in human amniotic fluid: comparison with other indices of assessing foetal lung maturity. AB - The concentration of the major surfactant-associated protein SP-A (28-36 kDa) was determined in 73 amniotic fluid samples obtained from normal (n = 40) and complicated (n = 33) pregnancies. Lecithin/sphingomyelin (L/S) ratio and phosphatidylglycerol (PG) levels were also determined in all the samples by one dimensional step-wise thin-layer chromatography. An enzyme-linked immunosorbent assay was used to determine human lung surfactant apoprotein SP-A. The amount of SP-A in human amniotic fluid increased as a function of gestational age from 8 mg l-1 at 36 weeks to 11.75 mg l-1 at 40-41 weeks of gestation. There was a significant difference (p less than 0.01) in amniotic fluid SP-A concentration from female (9.93 +/- 0.60 micrograms ml-1) compared to male (9.10 +/- 0.52 micrograms ml-1) foetuses. In amniotic fluid samples obtained from a group of complicated pregnancies, SP-A levels were significantly lower than in the normal group when adjusted for gestational age and sex of the foetus (p less than 0.05). PMID- 1514015 TI - Effects of pivalic acid-containing prodrugs on carnitine homeostasis and on response to fasting in children. AB - Treatment of 17 children aged 2-9.5 years with a combination of pivmecillinam and pivampicillin (250-500 mumol 24 h-1) for more than 1 year resulted in a reduction of the free carnitine concentration in serum and muscle to less than 10% of the mean reference value. The decline in serum was slow, with an estimated half-life of about 5 months. Spontaneous replenishment occurred at about the same slow rate. Thus, there is no increase in endogenous carnitine synthesis as a response to increased demand of carnitine for detoxification. Supplementation with carnitine during treatment required at least a four-fold molar excess over pivalic acid to achieve and sustain a normal carnitine concentration. The replenishment of carnitine occurred with a half-life of 1.1-3.0 months. From determination of muscle-carnitine concentration in patients treated with pivaloyl containing antibiotics and in patients with organic aciduris, we conclude that serum carnitine is a good predictor of carnitine stores in the body. Six non supplemented patients with a serum free-carnitine concentration of 0.7-2.6 mumol l-1 had an inadequate ketone-body increase during a 24-h fast. Vomiting, nausea and tiredness occurred in three cases following the fasting period. After normalization of the serum-carnitine concentration, a normal response to fasting was observed. Thus, in some organic acidurias, for example medium-chain acyl-CoA dehydrogenase deficiency, a low liver concentration of carnitine may be an important contributing factor to hypoglycaemic and Reye-like attacks. We believe that prodrugs which contain pivalic acid should be avoided if acceptable alternatives exist. If used, supplementation with at least four-fold molar excess of carnitine is advisable. PMID- 1514016 TI - Are ethane and pentane evolution and thiobarbituric acid reactivity specific for lipid peroxidation in erythrocyte membranes? AB - Peroxidation of human erythrocyte membranes was followed in vitro with head space analysis of ethane and pentane and a thiobarbituric acid assay in a standardized system liberating free oxygen radicals. Simultaneously, the decrease of the membrane palmitic, linoleic, arachidonic and docosahexaenoic acid was monitored. The recoveries of the peroxidation products of the red cell ghost preparations were compared with those obtained by peroxidation of pure fatty acids. Experiments using purified fatty acids revealed that ethane was preferentially produced from docosahexaenoic and linolenic, and pentane from linoleic and arachidonic acids. Thiobarbituric acid-reactive material (TBAR) was produced from each unsaturated fatty acid tested, but the amount was dependent on the number of carbon chain double bonds. During peroxidation of the erythrocyte ghosts, 72% of ethane and 51% pentane were produced during the first 12 h of incubation, whereas TBAR was produced at a constant rate throughout the 36-h test period. Hydrocarbon and TBAR production were similarly inhibited by desferoxamine (at p less than 0.005 and p less than 0.0001, respectively). The total recoveries of ethane, pentane and TBAR exceeded the amount expected by 7.8-, 1.4- and 5.5-fold, respectively. It was concluded that measurement of pentane is a reliable method to monitor lipid peroxidation during oxidative damage of the erythrocyte membrane. PMID- 1514017 TI - Glomerular filtration rate in pregnancy: a study in normal subjects and in patients with hypertension, preeclampsia and diabetes. AB - We have studied renal function during pregnancy using plasma clearance of iohexol to determine the glomerular filtration rate (GFR). In normal pregnancy, GFR was elevated by 40% throughout pregnancy and during the first week post partum, and fell to levels similar to those in non-pregnant women within 1 month. The development of GFR in diabetic pregnant women and in women with gestational hypertension was similar to that recorded in normal pregnancy. In subjects with preeclampsia the rise in GFR observed in normal pregnancy was absent, and no change in GFR was recorded after delivery. We conclude that the development of proteinuria and fluid retention typical of preeclampsia is paralleled by a deterioration of GFR. PMID- 1514018 TI - Proton magnetic resonance spectroscopy of fractionated plasma lipoproteins and reconstituted plasma from healthy subjects and patients with cancer. AB - Proton nuclear magnetic resonance spectra at 500 MHz of plasma and the very low density lipoprotein (VLDL), low density lipoprotein (LDL), and high density lipoprotein (HDL) fractions isolated by KBr gradient ultracentrifugation were analysed in 16 cancer patients, six pregnant and nine non-pregnant healthy subjects. In spectra with narrow plasma composite aliphatic peaks (methylene at 1.2-1.4 p.p.m. and methyl at 0.8-0.9 p.p.m., respectively), a relative increase in either VLDL, LDL, or both, or a decrease in HDL signals was observed. The mechanism for line-width narrowing seemed different in cancer patients (less signals from HDL relative to VLDL) compared with pregnant women (more signals from LDL). By reconstitution of plasma samples from both healthy subjects and patients with malignant disease, decreased concentration of VLDL or HDL resulted in broadening or narrowing of the composite peaks, respectively. The effects of VLDL and HDL on the plasma line width were moderated by the signals from LDL. Within lipoprotein fractions, the methylene and methyl resonances were shifted to a higher field with increased observation temperature, the change in shift being greatest for HDL. The line width of composite peaks in plasma varied with the observation temperature, depending on the relative concentrations of individual lipoproteins. The correlation coefficient (r) for the relation between total plasma triglyceride level and the average of the line-width of the composite methylene and methyl peaks was -0.78 (p less than 0.001). For spectra of individual lipoproteins, statistical significant relationships were found between line-widths and triglyceride content of the LDL fraction (methyl line-width, r = 0.63) (p less than 0.001) and between methylene line-width and cholesterol of HDL (r = 0.54) (p = 0.003). In summary, the shape and width of the composite aliphatic peaks of plasma were affected by the relative concentration, chemical shift and transition temperature of both VLDL, LDL, and HDL, and by the total triglyceride level. Comparing pregnancy and malignant disease, the lipoprotein resonances contributed differently in giving narrow composite signals. PMID- 1514019 TI - Enhanced urinary albumin excretion after 35 weeks of gestation and during labour in normal pregnancy. AB - This study reports on the urinary albumin to creatinine ratio during normal pregnancy, with special emphasis on the pre-delivery and labour periods. Albumin was determined in single voided urine specimens obtained from healthy non pregnant women (n = 16) and healthy pregnant women (n = 203; Groups A and B, 133 females examined during clinic visits and presentation at obstetric department; Group C, 70 females examined during labour) by radioimmunoassay (RIA). The mean ratio (+/- SD) for albumin/creatinine (A/Cr) in non-pregnant women was 1.46 +/- 0.32 mg mmol-1 Cr. Thus, 2.10 mg mmol-1 Cr (mean+2 SD) was considered to be the upper limit of normo-albuminuria. During pregnancy, 73% of the women (97 out of 133, Groups A and B) excreted less than or equal to 2.10 mg mmol-1 Cr. During the first 35 weeks of gestation, 30 of 34 pregnant women (88%) excreted less than or equal to 2.10 mg mmol-1 Cr, the mean being 0.93 +/- 0.64 mg mmol-1 Cr (median 1.0 mg mmol-1). During 36-42 weeks of gestation, the median A/Cr was 1.93 mg mmol-1 Cr (range 0.43-12.16) and 32 of 99 (32%) had values greater than 2.10 mg mmol-1 Cr, an increase of more than two-fold (p less than 0.031) compared with the first 35 weeks. During labour, 61% of non-haematuric urines (33 of 54, Group C) were greater than 2.10 mg mmol-1 Cr, being 125% greater (p less than 0.006) than that observed during pregnancy. Thus in normal pregnancy, A/Cr is increased during the late period of pregnancy and during labour. PMID- 1514020 TI - Comparison of the proportion of unconjugated to total serum cholic acid and the [14C]-xylose breath test in patients with suspected small intestinal bacterial overgrowth. AB - The proportion of unconjugated to total cholic acid in fasting serum and the 1 gram [14C]-xylose breath test were determined in 36 patients with suspected bacterial overgrowth of the small intestine. Twenty-two patients had an abnormal [14C]-xylose breath test, indicating bacterial overgrowth. The proportion of unconjugated to total cholic acid was significantly higher in the patients with an abnormal breath test compared with those displaying a normal breath test (47 +/- 5% vs 16 +/- 3%). A good correlation was obtained between the proportion of unconjugated to total cholic acid and the breath test (r = 0.63, n = 36). Provided the [14C]-xylose breath test is reliable as a test of bacterial overgrowth, determination of the proportion of unconjugated to total cholic acid in fasting serum had a sensitivity of 73% and a specificity of 94%. It is suggested that determination of the proportion of unconjugated to total cholic acid in peripheral venous blood may be useful as a simple screening test for detection of bacterial contamination of the upper small intestine provided the patients do not have bile acid malabsorption. PMID- 1514021 TI - Proposal of a new method to avoid misinterpretations in the evaluation of the leukergy test. AB - The leukergy test has been widely used in recent years to detect the phenomenon of leucocyte aggregation in various clinical conditions. It is performed by processing some drops of blood on a slide. According to the authors proposing this test, the leucocyte aggregation is expressed as the mean of the number of aggregates detected among 300 cells of a randomly chosen tract of two slides. We noted, however, that significant differences in the percentage of leucocyte aggregates were sometimes detected between two different slides prepared from the same patient, and hypothesized that an unequal distribution of aggregates along the slide could explain this finding. To test this hypothesis we analysed separately the leucocyte aggregates of three tracts of equal size of blood smears taken from 20 patients. Three slides, numbered 1, 2 and 3, were prepared from each patient. The first tract run by the drops when placing them in the slide showed a significantly lower percentage of aggregates than the remaining tracts (p less than 0.01 post hoc Tukey test). We conclude that the distribution of aggregated leucocytes is unequal along the slide and that the evaluation of the phenomenon of leukergy should always include the count of aggregates of the proximal, intermediate and distal tract of each slide. PMID- 1514022 TI - Anaplasmosis in Uganda. I. Use of dried blood on filter paper and serum samples for serodiagnosis of anaplasmosis--a comparative study. AB - The suitability of blood collected on filter papers in comparison with corresponding conventional serum samples in the diagnosis of bovine anaplasmosis was studied using the Complement Fixation Test (CFT), DOT-ELISA, Western immunoblot and Rapid Card Agglutination Test (RCAT). Dried blood on Whatman filter paper no. 1 was eluted in 1.8 ml of PBS 0.05% Tween 20 given an initial dilution of 1:100. The reactivity in both DOT-ELISA and Western immunoblotting was similar to that obtained with the sera diluted 1:100. Filter paper samples gave lower reactivity in all the tests as compared with corresponding serum samples. There was no significant difference in the reactivity between the eluates from filter papers stored at room temperature and those stored at 4 degrees C. Storage at room temperature did not significantly affect reactivity for up to 6 months. Eluates from filter papers stored for 6 months at room temperature continued to give similar reactivity to those from freshly prepared filter papers in both DOT-ELISA and Western blot, and in the Rapid Card Agglutination Test. It is concluded that collecting blood on filter papers is a suitable technique for large-scale screening and for seroepidemiological studies on anaplasmosis, and offers many advantages especially in developing countries where transport and cold chain facilities are a major constraint. PMID- 1514023 TI - Anaplasmosis in Uganda. II. Prevalence of bovine anaplasmosis. AB - The prevalence of bovine anaplasmosis was studied in 320 Zebu cattle randomly selected from three regions of Uganda (central, south-western and north-western) using DOT-ELISA, Western immunoblotting, Rapid Card Agglutination Test (RCAT), Capillary Tube Agglutination Test (CAT), Complement Fixation Test (CFT), and parasitological techniques. Dried blood on Whatman filter paper no. 1 was eluated in PBS 0.05% Tween 20 prior to testing at an initial dilution of 1:25. The incidence of parasitaemia ranged from 25% in the central region to 35% in the north-western region and the serological prevalence was lower in the central region and highest in the north-west. Prevalence rates assayed by DOT-ELISA and Western immunoblotting were 1.5-fold greater than those tested with RCAT and 3 fold greater than in CAT. The overall prevalence rates by DOT-ELISA and Western immunoblotting compared favourably with CFT data. The present data utilizing dried blood on filter papers indicate that there is a high prevalence of anaplasmosis in those regions of Uganda surveyed and it confirms our observations and those of others that collecting blood on filter papers is a suitable technique for large-scale screening and for seroepidemiological studies. PMID- 1514024 TI - Options for immunocontraception and issues to be addressed in the development of birth control vaccines. AB - Although the number of family planning methods currently available to couples has never been greater, the range and type of options are still not adequate to meet the widely varying personal needs and demands of individuals worldwide. Birth control vaccines offer a number of theoretical attractions although the development, preclinical and clinical testing of such vaccines pose a number of unique problems requiring novel solutions. If the on-going studies in this area are successful, a valuable new family planning method may be available by the end of the current decade. PMID- 1514025 TI - Anti-sperm and anti-ovum vaccines: the selection of candidate antigens and the outcome of preclinical studies. AB - A clear conceptual basis for anti-sperm and other modes of immunological birth control exists in spite of the limited basic research done on surface antigens of sperm or egg. In the normal physiological condition, the immune system does not respond to sperm, egg or fetus. Compared with anti-egg or anti-fetus immunocontraception, an anti-sperm vaccine has two theoretical advantages. First it would work in both males and females; second, it would not raise problems of autoimmunity in the female if a sperm-specific protein is used. However, for the development of such contraceptive vaccines the following scientific questions need to be resolved: (1) what surface protein to use as an antigen; (2) what adjuvant to use in humans for an anti-fertility vaccine; (3) how to maintain a high titre; (4) how the contraceptive effect will be terminated; and (5) what are the potential side-effects. PMID- 1514026 TI - Anti-hCG vaccines are in clinical trials. AB - Two vaccines inducing antibodies against human chorionic gonadotropin (hCG) have completed Phase I clinical trials, indicating the reversibility and safety of these vaccines. One is currently in Phase II efficacy trials in women in three major centres in India. The available data suggest that the vaccine prevents pregnancy above antibody titres of 50 ng/ml hCG bioneutralization capacity. PMID- 1514027 TI - Anti-LHRH and anti-pituitary gonadotropin vaccines: their development and clinical applications. AB - Active immunization against hormones involved in the regulation of reproduction is a promising approach to immunocontraception. The hypothalamic peptide, LHRH, controls the synthesis and release of the pituitary gonadotropins, LH and FSH, which regulate gonadal steroidogenesis, sperm production, follicular development and ovulation. Immunizing female primates against LHRH or LH induces infertility, but also disrupts the menstrual cycle. Immunization against the beta subunit of the placental hormone, chorionic gonadotropin (hCG), or its fragment prevents pregnancy without interfering with menstrual cycles or ovulation. hCG vaccines have reached the stage of clinical trials. FSH and LHRH have been tested for immunocontraception in male primates. While active as well as passive immunization against FSH reduced spermatogenesis severely, azoospermia could not be achieved consistently. Immunization against LHRH effectively suppressed spermatogenesis in rats and rabbits. Normal sexual behaviour was maintained by concomitant androgen administration. Fertility was restored when antibody titres declined and no adverse effects were observed. A number of LHRH vaccine preparations are being tested in men in several countries, including the United States. Since the LHRH vaccine reduces serum testosterone levels the first clinical studies involve men with prostate cancer. These trials will be followed by immunization of normal men if the antibody response is sufficient and no adverse effects are observed. PMID- 1514028 TI - Anti-trophectoderm vaccines: rationale and methods used for antigen identification and selection. AB - Trophoblast, forming a continuous interface at the maternal-fetal junction, is of considerable interest to biologists. An area of recent research is the search for trophoblast-specific antigens. It is believed that identification and characterization of these antigens may have many practical applications such as in development of contragestational vaccines. To be acceptable for humans such a vaccine will need to be effective before the completion of implantation and appearance of the primitive streak about 14 days after fertilization. This will not alter the menstrual cycle or the time of menses. Vaccines having a later effect resulting in termination of pregnancy after this time would be considered abortifacients. Although logistical and ethical considerations necessitated the use of post-implantation human trophoblast in WHO Birth Control Vaccine studies, the antigens isolated from such tissues would need to be expressed and be detectable on the surface of pre-implantation trophectoderm if they are to represent appropriate candidates for vaccine development. The criteria for identification and selection of these antigens will be reviewed. PMID- 1514029 TI - Future perspectives for vaccine development. AB - The successful development of an anti-fertility vaccine necessitates overcoming obstacles in eliciting an immune response to self species body constituents. The feasibility of accomplishing this task has been demonstrated for certain antigens described in this workshop; however, additional vaccine candidate antigens may yet be revealed from the application of recent advances in molecular biology. Improvements in vaccine design are likely to occur from discovery of more appropriate epitopes on targeting antigens, new carrier molecules for terminating immunological tolerance, expression of vaccine antigens in suitable live vectors, the co-immunization with more than one antigen, the use of safer and/or more effective adjuvants and vehicles, more efficient immunization by targeting antigens to specific lymphoid cells, and the development of superior vaccine delivery systems. Research directed to restricting the immune response to the genital tract and to intentionally reverse the effects of immunization will likely be pursued in the future. All of these areas need to be addressed if vaccines are to be developed that are not only safe and effective but also highly acceptable as birth control methods. PMID- 1514030 TI - Immunological techniques in and for developing countries. PMID- 1514031 TI - Immunoblot analysis of sera from Ethiopian cutaneous leishmaniasis by antibody class. AB - We have determined the specificity of the classes of anti-leishmanial antibodies which are detectable in serum from patients with active cutaneous leishmaniasis. On immunoblots, differences exist in the patterns of antigen recognition by IgG, IgM, IgA and IgE antibodies present in localized cutaneous leishmaniasis (LCL) and diffuse cutaneous leishmaniasis (DCL) patient serum. Each class of antibody showed differing patterns of banding to the various molecular species of parasite antigens. There was significant variation in the specificities of the IgG antibody reactivities between individual patients. The patterns of IgM binding were generally homogeneous and restricted to antigens with M(r) greater than 40 kDa. The only class of anti-Leishmania antibodies which showed shared patterns of common antigen recognition by all of the patients studied were IgA antibodies. The reactivities of IgE antibodies encompassed two antigens of M(r) 36 and 46-48 kDa which were not recognized by any of the other isotypes. Such antibody class associated reactivity may be useful in the design of serodiagnostic assays for the detection of Leishmania infection or other infectious agents. PMID- 1514032 TI - Determination by Widal agglutination of the baseline titre for the diagnosis of typhoid fever in two Nigerian states. AB - This study was carried out in Borno and Plateau States of Nigeria to determine the baseline titre for the diagnosis of typhoid fever using a single Widal test. Of 172 patients with symptoms and signs of typhoid fever, 92.4% and 90.7% had reciprocal O and H antibody titres respectively of 160 or above. On the other hand, 95.3% and 66.3% of the 937 healthy control subjects had reciprocal O and H antibody titres respectively of 80 or less. The results of this study suggest that in Borno and Plateau States of Nigeria a reciprocal O antibody titre of 160 and above in persons with illness whose symptoms and signs are compatible with typhoid fever could be considered diagnostic using the single Widal test. PMID- 1514033 TI - Cytokine responses to parasite antigens: in vitro cytokine production to promastigotes of L. aethiopica by cells from non-Leishmania exposed donors may influence disease establishment. AB - The various cytokine responses associated with stimulation by parasites is discussed with emphasis on Leishmania parasites. Cells from normal individuals can respond to Leishmania antigens in vitro but the state of the antigen used for stimulation influences the outcome. We have used cells from non-Leishmania exposed donors and stimulated them in vitro with variously treated promastigotes of L. aethiopica. The levels of some cytokines released into the supernatant were measured. All the Leishmania preparations tested induced high levels of IL-6, whereas IFN-gamma production to the different stimuli was variable in the individual donors. The ability of these supernatants to inhibit intracellular forms of L. aethiopica was sometimes stronger in L. aethiopica-induced than in PHA-induced cultures. Such strong non-Leishmania specific responses, if they exist in vivo, may influence whether disease is established when the host encounters Leishmania parasites. PMID- 1514034 TI - Reduced natural killer cell activity in multi-drug resistant pulmonary tuberculosis. AB - Cellular immune status in five patients with multi-drug resistant pulmonary tuberculosis was investigated and compared with five matched controls with non resistant tuberculosis. A significant reduction in fresh natural killer (NK)-cell activity was found in the resistant group (P less than 0.005). There were no significant differences between the two groups in lymphocyte phenotype, proliferation or PPD-specific cytotoxicity. Reduced NK-cell function may play a role in the pathogenesis of multi-drug resistant pulmonary tuberculosis. PMID- 1514035 TI - Identification of anti-Plasmodium falciparum antibodies in human breast milk. AB - Malarial infections are rarely observed in neonates. It has been postulated that some immunity may be passively transferred during nursing, but anti-malarial antibodies (Abs) have not been detected in human milk. In this study, milk samples, collected 2-14 days after parturition from women at the Central Maternity Hospital, Yaounde, were evaluated for total IgG and IgA antibody levels by radial diffusion, protein composition by SDS-PAGE, anti-malarial antibodies using an isotype-specific immunofluorescence assay, and the ability to immunoprecipitate Plasmodium falciparum antigens metabolically labelled with 35S methionine. Results showed that anti-P. falciparum antibodies were present in breast milk, and that paired milk and serum samples from individual women contained Abs that recognized similar malarial antigens. PMID- 1514037 TI - Ocular and systemic determination of IL-1 beta and tumour necrosis factor in a patient with ocular inflammation. AB - Cytokines such as interleukin-1 beta (IL-1 beta) and tumour necrosis factor (TNF) may play an important role in ocular inflammation. We studied a patient with clinical features of sympathetic ophthalmia secondary to previous penetrating ocular injuries, and compared the ocular and systemic levels of IL-1 beta and TNF to control serum, and correlated these findings to histopathological sections of the patient's eye. Histology showed the presence of a diffuse chronic inflammatory infiltrate within the choroid and in a perivascular distribution in the retina. The significantly elevated ocular and systemic levels of IL-1 beta and TNF suggest that there is not only a localized ocular response but a systemic response as well. The presence of IL-1 beta TNF may play a role in the pathogenesis of ocular inflammation once the blood ocular barrier has been breached and ocular antigens have been exposed to the systemic immune system. PMID- 1514036 TI - Serum interleukin (IL-1 beta) in patients with diffuse scleritis. AB - Scleritis is a painful, destructive inflammatory eye disease. We measured serum IL-1 beta in ten patients with diffuse scleritis and in control subjects matched for age and sex. Patients with diffuse scleritis were found to have significantly elevated serum concentrations of IL-1 beta in comparison to normal subjects (P less than 0.02). The results suggest that IL-1 beta is associated with diffuse scleritis and may influence scleral breakdown in diffuse scleritis. PMID- 1514038 TI - Cells from healthy non-exposed individuals produce cytokines to selected fractions of Leishmania promastigotes. AB - We are interested in cellular responses to antigens of parasites to which the cell donor has not been previously exposed and how such responses may influence parasite establishment. In order to characterize such responses we have used cells from unexposed healthy donors and analysed the lymphoproliferative response to various Leishmania aethiopica antigen preparations and the cytokines produced in the process. Peripheral blood lymphocytes were stimulated with SDS-PAGE separated L. aethiopica antigen coupled to nitrocellulose particles. Fifteen of the 16 unexposed individuals tested had proliferative responses to either the whole or/and the antigen-bearing nitrocellulose fractions (NC fractions). Although the degree of response to the fractionated antigen varied in individuals, major stimulatory fractions were found in the high molecular weight region of 110-80 kDa (fractions 3-6) and low molecular weight region of 46-18 kDa (fractions 12-16). Substantial amounts of interferon gamma (IFN-gamma) and interleukin 2 (IL-2) were present in the supernatants of cells stimulated with the whole unfractionated antigen. The potential relevance of such responses in resistance to Leishmania infection is discussed. PMID- 1514039 TI - Generation of lymphokine-activated killer cells by adherent LGL phenotype cells and non-adherent T lymphocytes. AB - In this work we separated human blood lymphocytes (PBL) in two populations (A-LAK and NA-LAK cells) by the adherence plastic method. A maximum adherence of cells was obtained after 2 days of PBL incubation in LAK medium containing 500 U/ml rIL 2. The A-LAK cells had LGL phenotype but 40% of them had a macrophage phenotype marker and less than 20% weakly expressed a T-cell marker. This population, when reincubated in culture, produced an increasing titre of interferon. At the same time, a significant NK activity against K562 target cells was measured just after enrichment; these enriched adherent cells also developed an increased LAK activity against DAUDI cell lines, ninefold more at 6 days than when assayed just after enrichment. In contrast, 75% of the NA-LAK enriched cells expressed T-cell marker; these produced two- to threefold less interferon than A-LAK cells at all time-points. The NA-LAK lymphocytes enhanced principally LAK activity measured by 70% lysis against DAUDI target cells tested at 6 days of culture. Further studies are in progress to determine the nature of the effector cells that mediated LAK activity. PMID- 1514040 TI - Post-mortem HLA tissue typing of retinal pigment epithelial cells. AB - Retinal pigment epithelial cells (RPE) were derived from bulbi of cornea donors and maintained in culture. The time-span between donor's death and cell cultivation ranged from 2 to 122 h. The mean numbers of hours was 25.6 (n = 130). After IFN-gamma stimulation, cells were serologically typed for class I and class II antigens. Unclear class I allospecificities were verified by one-dimensional isoelectric focusing. Data from the serological typing of lymphocytes and those of the serological and biochemical typing of RPE from the same donors were compared in 22 cases. There was a discrepancy of less than 5%, whereby either the typing on lymphocytes could not identify some specificities declared as blanks or the RPE typing had failed to clearly define a specificity. Our data show that the strategy adopted here is very successful for tissue typing post mortem, thus increasing the number of available HLA-matched corneas and consequently reducing the number of corneal graft rejections. PMID- 1514041 TI - Reactivity of some monoclonal antibodies specific for human lymphocytes with vervet monkey peripheral blood mononuclear cells. AB - Reactivities of some monoclonal antibodies to human lymphocyte surface antigens were tested on vervet monkey peripheral blood mononuclear cells (PBMC), using flow cytometry and immunoperoxidase techniques. A number of antibodies were identified which reacted with similar populations of lymphocytes from vervet monkeys. These included antibodies that define T cells, suppressor/cytotoxic cell subset, pan B cells, monocytes and MHC class I and II. A number of anti-CD4 markers examined were unsuitable for use in the vervet system. PMID- 1514042 TI - Immunological consequences from exposure to benzo(a)pyrene during pregnancy. AB - Progeny and maternal immune status after benzo(a)pyrene (BP) exposure of mothers at mid-pregnancy is disrupted in fetal liver (FL), in spleen and in thymus during pregnancy and postnatally. Mice suffer deficiencies in splenic and thymic mixed lymphocyte responses (MLR), and disorientations of T antigen expressing cells, punctuated by exorbitant increases in Lyt2, especially in FL. FL Lyt2 do not suppress an MLR, while Lyt1 mediate suppression. Isolated Thy1 show a weak response to Concanavalin A; FL Thy1 weakly express an MLR. Maternal macrophages and progeny B cells are also functionally abnormal. Thus, BP induces generalized immune deficiency that may affect ontogeny and which is potentially deleterious to health. PMID- 1514043 TI - Iron deficiency and immune responses. AB - Iron deficiency is often associated with the impairment of the immune system, particularly the functioning of T-cell lymphocytes. Studies were therefore carried out in mice to investigate the involvement of iron in T-cell functions. Iron deficiency in mice was induced nutritionally by feeding diets differing in iron content for 4 weeks to produce normal, moderately low and severely low haematological indices. The proliferation of lymphocytes stimulated by Con A from these groups of mice was significantly affected by the degree of iron deficiency. Iron depletion also resulted in decreased production of interleukin 2 (IL-2) in the proliferating cells. The implications of these findings in the manifestation of iron deficiency anaemia are discussed. PMID- 1514044 TI - IgG subclass values from normal children in Cape Town. AB - Sensitive and reproducible enzyme-linked immunoabsorbent assays (ELISA) have been developed to quantitate IgG subclass levels using monoclonal antibodies. Normal values for serum IgG subclass levels were determined in 300 healthy children between 6 months and 14 years of age and in 80 adults. High levels of IgG1 and delayed maturational development of IgG2 in children from Cape Town are different to results reported from developed countries. Genetic differences may account for this. PMID- 1514045 TI - Report on the AIDS workshop. PMID- 1514046 TI - Vaccination of the vervet monkey (Cercopithecus aethiops) against infection with Schistosoma mansoni. AB - Pilot experiments were carried out to assess the immunizing potential of radiation-attenuated cercariae of S. mansoni. Groups of 4 monkeys each were vaccinated 4-5 times at 3-5-week intervals using cercariae which had received 10, 20, 40 or 60 krad of gamma radiation. Animals were vaccinated with 1000 or 2000 cercariae per kilogram of body weight. Overall the difference in worm burdens between the vaccinated and unvaccinated groups was highly significant (P greater than 0.01). The highest level of protection achieved was 44.4%. This was in monkeys which were immunized five times with 2000, 20-krad cercariae at 3-4-week intervals. Protection levels of 33.3%, 36.6% and 37.0% were achieved in groups which had received, respectively, 1000 20-krad cercariae, 1000 10-krad cercariae, 2000 40-krad cercariae and 2000 60-krad cercariae. Vaccination reduced faecal egg counts markedly and intestinal tissue egg counts by 20-40%. Antischistosomular antibody was detectable in vitro 3 weeks after the first vaccination. Schistosomule kill rates of up to 60% were observed in vitro. PMID- 1514047 TI - Immune responses after treatment for Schistosoma mansoni infections. AB - The changes in the immune responses of patients before and at 3 weeks after treatment with anti-schistosomal drugs were investigated. Lymphocyte responses to Concanavalin A and to worm antigens were inhibited after treatment, whereas responses to cercarial and egg antigens remained unchanged. Eosinophil levels were significantly elevated after treatment and were positively correlated with the increase in anti-worm antibodies (r = 0.587), and negatively associated with anti-egg antibodies (r = -0.727). Although the eosinophil-dependent cytotoxicity to schistosomula was not significantly enhanced after treatment, some increased killing was evident of half the patients (7/15). On the other hand, the ability of adherent mononuclear cells to stimulate eosinophil functions was markedly enhanced by treatment (P less than 0.001). These studies suggest that treatment may enhance some of the potentially protective host's immune mechanisms. PMID- 1514048 TI - Isolation and properties of 600-kDa and 23-kDa haemolymph proteins from the tsetse fly, Glossina morsitans: their possible role as biological insecticides. AB - The haemolymph of the tsetse fly, Glossina morsitans morsitans, contains a high (lipophorin) and a low molecular weight protein of high densities, 1.11 and 1.29 g/ml, respectively. The purification of the proteins was achieved by a combination of density gradient ultracentrifugation and reported gel permeation chromatography. The lipophorin is of high molecular weight (M(r) integral of 600,000) and consists of two apoproteins, apolipophorin I (M(r) integral of 250,000) and apolipophorin II (M(r) integral of 80,000) both of which are glycosylated. Lipophorin also has a pI of 6.1. However, electrophoresis under non denaturing and denaturing conditions showed the low molecular weight protein to be a single polypeptide chain (M(r) integral of 23,000). Amino acid analysis revealed a relatively high content of the acidic amino acids as well as serine and glycine. The protein contained lipids as shown by Sudan Black staining but was unglycosylated. Using rabbit antiserum against the isolated protein in immunodiffusion and immunoblotting experiments, no cross-reactivity was detected with haemolymph samples from insects representing six orders. In conclusion, the finding of lipophorin suggests that, although flies primarily utilize proline for their energy needs, there is an active transport mechanism for the supply of lipid requirements. However, the results for the low molecular weight protein indicate that the protein is unique to Glossina, suggesting that it may have an important role in the physiology of this insect and is therefore a significant target for vector management. PMID- 1514050 TI - Science and research in Africa. PMID- 1514049 TI - IFN-gamma and delayed-type hypersensitivity are associated with cutaneous leishmaniasis in vervet monkeys following secondary rechallenge with Leishmania major. AB - IFN-gamma levels and delayed-type hypersensitivity (DTH) responses were evaluated in vervet monkeys, following secondary infection with Leishmania major (L. major). The animals had previously been vaccinated with leishmanial antigen, exposed to a primary infection and allowed to self-cure. Supernatants of peripheral blood mononuclear cell (PBMC) cultures, stimulated with either L. major antigen or Concanavalin A (Con A), were examined for the presence of IFN gamma in a double sandwich enzyme-linked immunosorbent assay (ELISA). Significant levels of IFN-gamma were detected during active disease and following self-cure in both antigen and Con A supernatants. Higher levels of IFN-gamma were, however, present during active disease as compared with after self-cure. Positive and strong DTH responses were elicited in all experimental animals, following intradermal injection of fixed promastigotes (5 x 10(7)/animal) before rechallenge, during active infection and following self-cure. Again, strongest DTH responses were obtained during active infection as compared with the other sampling points. There was a correlation between IFN-gamma levels and DTH responses. It was concluded that IFN-gamma secretion and positive DTH responses are associated with secondary L. major infection and represent specific immunological correlates of protection in this disease model. PMID- 1514051 TI - Anti-Onchocerca volvulus immunoglobulin subclass response in children from Sierra Leone. AB - The humoral immune responses of a paediatric population of 224 children, 2-15 years of age, residing in an onchocerciasis endemic area of Sierra Leone, were studied to gain information that may be useful in the serodiagnosis of prepatent and low-level infections with Onchocerca volvulus. The antigen-specific levels of IgG and IgG4 were determined and evaluated in the context of the parasitological status of the child. Over 87% of the microfilaria-negative children had significant levels of antigen-specific antibodies against O. volvulus, suggesting that a large percentage of this paediatric population were harbouring prepatent or low-level infections. Over 60% of the children in the group that had detectable numbers of microfilariae in skin snips had elevated levels of O. volvulus-specific IgG4. In contrast, only 23% of the microfilaria-negative children had detectable IgG4 responses. The results presented here indicate that measures of O. volvulus-specific IgG4 may be a useful indicator of the parasitological status of children during the very early stages of onchocerciasis. PMID- 1514052 TI - Cell-mediated and monoclonal antibody-dependent killing of Onchocerca volvulus microfilariae. AB - To identify the target antigens implicated in the adherence and killing of microfilariae (mf) by leucocytes, we incubated nodular mf and leucocytes in the presence of anti-cuticular monoclonal antibodies (MOVs) and fresh serum. Leucocyte donors were patients with a mean age of 37 years (with 0-1 mf/snip), who had lived in the endemic village studied for at least 10 years. After 16-20 h of incubation, up to 74% of the mf could be seen with 10 or more cells adhering to them. By 36-40 h up to 54% of the mf had been killed by the leucocytes in the presence of a cocktail of monoclonal antibodies termed MOV GIV. The degree of killing in control experiments with the monoclonal antibody MOV 1 remained lower (P less than 0.05), ranging from 0.0 to 4.5% of mf with initial viability of 90 95%. Western blotting revealed MOV GIV prominent target antigens of 10.5, 18.0, 23.5 and 27 kDa in crude surface extracts of female O. volvulus. The detected antigens may play a role in host protection. PMID- 1514053 TI - Cloning and sequencing of hepatitis B virus pre-S and S gene regions. AB - The polymerase chain reaction (PCR) was used to amplify the pre-S1, pre-S2 and S gene regions of hepatitis B virus (HBV). Sera from three different patients were used as the source of HBV DNA. The resulting 1.2-kb amplification product was cloned into the plasmid pIBI30. Restriction enzyme analysis revealed that there are two BamHI sites located about 300 bp apart within the S gene. DNA sequencing revealed a greatest homology to the HBVadw subtype. PMID- 1514054 TI - Herpes zoster ophthalmicus: an early pointer to HIV-1 positivity in young African patients. AB - We studied prospectively 30 patients, seen over 10 months, who had herpes zoster ophthalmicus (HZO) and who were classified by age, sex, ophthalmological observations and HIV-1 status. Of patients who presented with HZO, 40% were HIV positive, and the majority were less than 40 years of age. The clinical manifestation of HZO has a high positive predictive value for HIV positivity in young patients with this viral infection. PMID- 1514055 TI - Evidence of immunosuppression by bovine respiratory syncytial virus. AB - Respiratory syncytial virus (RSV) is a major respiratory pathogen in human infants and calves. Calves and lambs infected with bovine RSV show mild clinical signs but they are more susceptible to secondary infection with Pasteurella haemolytica. Lambs infected with P. haemolytica 6 days after experimental infection with bovine RSV had significantly greater magnitudes of fever, higher disease and lesion scores and higher mortality rates than those infected with P. haemolytica or bovine RSV alone (P less than 0.05). Experimental infection with bovine RSV is characterized by alterations in lymphocyte subpopulations and down regulation of some of their functions. For example, the number of T helper cells is significantly reduced during the first week of infection and peripheral blood mononuclear cells obtained from bovine RSV-infected lambs were less responsive to the mitogen phytohaemagglutinin but more susceptible to P. haemolytica cytotoxin than those obtained from control lambs. Infection with bovine RSV does not significantly affect the humoral immune responses of lambs against P. haemolytica cytotoxin. Bovine RSV does not appear to affect the capacity of alveolar macrophages to present antigens in vitro. PMID- 1514056 TI - 'Silent' HIV infection among wives of seropositive HIV carriers in the Ethiopian community in Israel. AB - We have previously described the phenomenon of 'silent HIV carriers', i.e. individuals with HIV specific immunity and a positive PCR for HIV-1, yet HIV seronegative. In the present study, we have looked for such 'silent' carriers among wives of individuals infected with HIV in Africa (Ethiopia). In addition to determining HIV serology, peripheral blood mononuclear cells (PBMC) were tested by PCR for HIV-1 and for their ability to generate specific antibodies to HIV upon polyclonal B-cell activation (P-BAT). Out of 16 wives so tested, three were HIV seropositive and among the 13 seronegatives, eight were P-BAT positive and five were both P-BAT and PCR positive. These findings suggest that (1) 'silent' HIV carriers may indeed be present in African populations; (2) interpretation of the 'silent' carrier phenomenon is not clear and will depend on clinical follow up and the ability to culture virus from such carriers; and (3) results of HIV serology in this population and probably in other African populations should be viewed with caution. PMID- 1514057 TI - Tuberculosis and leprosy: attempts to identify T-cell antigens of potential value for vaccine design. AB - Tuberculosis and leprosy are chronic bacterial infectious diseases which represent major health problems worldwide. It is generally accepted that, on the one hand, effective vaccination strategies are required for satisfactory control of these diseases and, on the other hand, that currently available vaccination measures are insufficient for this purpose. Ideally, a subunit vaccine should be designed which is composed of one or a few protective antigens. In this brief treatise our approach towards the identification of antigens with potential value for vaccine design is described. It comprises high resolution fractionation by two-dimensional gel electrophoresis, transfer of separated fractions by electroelution and testing of separated fractions with viable T cells and accessory cells. Using this approach we find: (1) multiple antigens are recognized by T cells from leprosy and tuberculosis patients as well as healthy contacts; (2) apparently, suppressive antigens exist in leprosy; (3) an antigen cluster which is apparently indicative for immunity against M. tuberculosis is present among secreted proteins. We hope that further improvement of this methodology will help in the rational design of subunit vaccines against tuberculosis and leprosy. PMID- 1514058 TI - Serodiagnosis of bacterial diseases: problems and developments. AB - Serodiagnosis is useful when pathogens cannot be detected quickly or easily by conventional methods or have been eliminated by the patient. Taking the example of leptospirosis, the microscopic agglutination test to detect specific antibodies after leptospires have disappeared from the patient's bloodstream is of unsurpassed reliability. Unfortunately the test is used mainly in specialized laboratories that can culture leptospires to serve as live antigens. Freeze-dried leptospires may allow the application of the test on a wide scale. The ELISA is useful for the detection of IgM antibodies in humans as a sign of current or recent infection. ELISA results must be confirmed by the microscopic agglutination test. A simplified easy-to-read ELISA using broadly reactive antigen for the detection of all types of leptospires might be useful for a quick detection of acute human leptospirosis. Using an appropriate antigenic preparation the ELISA is useful for the detection of antibodies in animals, e.g. cattle. As for pathogen detection, DNA-based methods such as PCR are promising for an early, quick and specific diagnosis. Antigenic analysis by monoclonal antibodies and genetic analysis by restriction fragment length polymorphism are for the time being complementary methods for the characterization of leptospiral isolates. PMID- 1514059 TI - Specific IgG subclass antibody levels and phagocytosis of serotype 14 pneumococcus following immunization. AB - Complement and specific antibody directed against capsular polysaccharide are necessary for efficient phagocytosis of pneumococci. In normal adults, specific antibody to pneumococci is predominantly of the IgG2 subclass. However, the role of IgG2 in bacterial clearance is debatable. We therefore decided to investigate the relationship between specific IgG subclass antibody levels and phagocytosis of serotype 14 pneumococcus, before and after immunization with a pneumococcal capsular polysaccharide vaccine. Specific IgG subclass antibody was measured by an ELISA technique and the effect of serum on phagocytosis of radiolabelled pneumococci by normal polymorphs was determined. We found that in the presence of complement, phagocytosis correlated significantly with both specific IgG1 and IgG2 antibody titres (r = 0.547, P = 0.002 and r = 0.464, P = 0.009, respectively). However, in decomplemented sera, the correlation with IgG1 antibody was lost, whereas that with IgG2 antibody was strengthened (r = 0.641, P = less than 0.001). The possibility that IgG2 binds to receptors on polymorphs should be considered. PMID- 1514060 TI - Humoral factors of natural resistance of Bos indicus cattle selected for antibody titre to Brucella abortus. AB - The concentration of lysozyme, total immunoglobulin and bactericidal activity were measured in sera of Bos indicus cattle, retrospectively screened for specific antibodies to Brucella abortus and classified as being positive reactors or negative reactors. In addition, the effect of complement in the sera was studied to demonstrate complement dependence of antibody-mediated bacterial killing. It was observed that, under the test conditions, serum bactericidal activity and concentration of total immunoglobulin were associated with high specific antibody levels (P less than 0.001). Furthermore, there was a slight decrease in the lytic activity of lysozyme in the sera of animals with high antibody titres. PMID- 1514061 TI - Occupational exposures to aerosolized pharmaceuticals and control strategies. PMID- 1514062 TI - Control of anesthetic gases in dental operatories. PMID- 1514063 TI - Study design for the characterization of aerosols during surgical procedures. PMID- 1514064 TI - Comparison of job demands, control and psychosomatic complaints at different career stages of managers in Finland and the United States. PMID- 1514065 TI - Stress symptoms, burnout and suicidal thoughts of Finnish physicians. PMID- 1514066 TI - Application of a portable test battery in the assessment of fatigue in laboratory and worksite studies of 12-hour shifts. PMID- 1514067 TI - Relation of age to circadian adjustment to night work. PMID- 1514068 TI - Psychosocial and work organization risk factors for cumulative trauma disorders in the hands and wrists of newspaper employees. PMID- 1514069 TI - Stress and change among bank directors and supervisors. PMID- 1514070 TI - Ergonomic analysis to characterize task constraint and repetitiveness as risk factors for musculoskeletal disorders in telecommunication office work. AB - A modified activity analysis procedure was devised to quantify the presence of two task attributes identified in previous research as contributing to an increase in work demands and ergonomic hazards. The purpose of this study was to develop an exposure index based on the presence of two task attributes. The utility of this job activity analysis will, of course, be determined by the extent to which workers with varying degrees of muscular pain and discomfort correspond to the risk exposure group we have described. The results of both the medical and psychological assessments of the workers--contained in the final HETA report--will be used to assess the utility of our method and determine whether the task attributes of constraint and repetitiveness contribute to the onset of cumulative trauma disorders among clerical workers. PMID- 1514072 TI - Work load, psychophysiological strain and coping of innovation project management in industry. PMID- 1514071 TI - Occupational musculoskeletal disorders among supermarket cashiers. PMID- 1514073 TI - Measurement of salivary immunoglobulin A as an immunologic biomarker of job stress. PMID- 1514074 TI - Coping with job stress by managers at different career stages in Finland and the United States. PMID- 1514075 TI - Work and retirement attitudes of 50- to 64-year-old people at work and on pension. PMID- 1514076 TI - Reference values for amplitudes and conduction velocities obtained from a cohort of middle-aged and retired workers. PMID- 1514077 TI - Prevention of reproductive health hazards at work. PMID- 1514078 TI - Data gaps and new methodologies in the assessment of male fecundity in occupational field studies. PMID- 1514079 TI - Power analyses and immunoassays for measuring reproductive hormones in urine to assess female reproductive potential in field studies. PMID- 1514080 TI - Effects of parental occupational exposure to solvents and lead on spontaneous abortion. PMID- 1514081 TI - Epidemiologic studies of adverse reproductive outcomes in working populations. PMID- 1514082 TI - Reproductive toxicity of ethylene glycol monomethyl ether, ethylene glycol monoethyl ether and their acetates. PMID- 1514083 TI - A model agricultural health promotion systems program for building state-based agricultural safety and health infrastructures. PMID- 1514084 TI - Implications for the use of E codes of the International Classification of Diseases and narrative data in identifying tractor-related deaths in agriculture, United States, 1980-1986. PMID- 1514085 TI - Priority setting and evaluation as tools for planning research strategy. AB - The growing role of research as a factor for socioeconomic development has also stimulated efforts for setting priorities and for evaluating research strategies. Priorities can be set for problems which are known for their consequences or their existing characteristics. The only way to ensure research on new problems is to allow more space for basic research aimed at revealing new data and at describing new phenomena. Evaluation methods for applied research are available, and they have been successfully used for making research units more effective and for improving the quality of the research in question. PMID- 1514086 TI - Morbidity and risk factors of Finnish farmers. PMID- 1514087 TI - Occupational fatalities in the fishing, logging and air transport industries in Alaska, 1991. PMID- 1514088 TI - Endotoxin and complement activation in an analysis of environmental dusts from a horse barn. PMID- 1514089 TI - Analysis of environmental histamine from agricultural dust. PMID- 1514090 TI - Development of analytical methods for agricultural chemicals. PMID- 1514091 TI - Evaluative research and methods development for the assessment of training effectiveness in occupational respiratory protection. PMID- 1514092 TI - Biological monitoring at the Institute of Occupational Health. PMID- 1514093 TI - Measurement of interleukin 1 in pulmonary reactions induced by agricultural dusts. PMID- 1514094 TI - Interleukin 1 and its inhibition in an inflammatory reaction caused by Aspergillus umbrosus. PMID- 1514095 TI - Biological monitoring for occupational exposures to ortho-toluidine and aniline. PMID- 1514096 TI - Work ability of aging workers. PMID- 1514097 TI - Response of the National Institute for Occupational Safety and Health to an occupational health risk from exposure to ortho-toluidine and aniline. PMID- 1514098 TI - Use of biomarkers of occupational musculoskeletal disorders in epidemiology and laboratory animal model development. PMID- 1514099 TI - Occupational injuries and fatalities among health care workers in the United States. PMID- 1514100 TI - Work organization and well-being of Finnish health care personnel. PMID- 1514101 TI - Continued need for strategies to prevent needlestick injuries and occupational exposures to bloodborne pathogens. PMID- 1514102 TI - Health care workers, tuberculosis, and the human immunodeficiency virus epidemic. PMID- 1514103 TI - Arctic contaminants: sources, occurrence and pathways. AB - Potentially toxic organic compounds, acids, metals and radionuclides in the northern polar region are a matter of concern as it becomes evident that long range transport of pollution on hemispheric to global scales is damaging this part of the world. In this review and assessment of sources, occurrence, history and pathways of these substances in the north, the state of knowledge of the transport media--the ocean and atmospheric circulation--is also examined. A five compartment model of the northern region is developed with the intent of assessing the pathways of northern contaminants. It shows that we know most about pathways of acids, metals and radionuclides and least about those of complex synthetic organic compounds. Of the total annual inputs of anthropogenic acidic sulphur and the metals lead and cadmium to the Arctic via the atmosphere, an estimated 10-14% are deposited. A water mass budget for the surface layer of the Arctic Ocean, the most biologically active part of that sea, is constructed to examine the mass budget for one of the major persistent organochlorine compound groups found in remote regions, hexachlorocyclohexanes (HCH), one isomer of which is lindane. It is concluded that both the atmosphere and the ocean are important transport media. Even for the HCH substances which are relatively easily measured and simple in composition compared to other synthetic organics, we know little about the occurrence and environmental physical/chemical characteristics that determine pathways into the food chain. More environmental measurements, chemical characterization studies and environmental chemical transport modelling are needed, as is better knowledge of the circulation of the Arctic Ocean and the marine food web. PMID- 1514104 TI - Presence and implications of chemical contaminants in the freshwaters of the Canadian Arctic. AB - Hydrocarbons, stable organochlorines, metals and radionuclides are widespread in the freshwaters of the Canadian Arctic. Petroleum-associated hydrocarbon sources include natural seepage, wastes and effluents from exploration, production and refining at Norman Wells and spills. Hydrocarbons also originate from combustion of carbon-based fuels, generally at lower latitudes and then reach the Arctic with air movements. Organochlorine compounds also move throughout the hemisphere by aerial pathways and have become distributed widely in Arctic fish. The organochlorine at highest concentration in Arctic freshwater is alpha-HCH, while those generally at highest concentrations in the fish are toxaphene, PCBs and chlordane. Metals are ubiquitous in Arctic freshwaters, with inputs of several metals by precipitation superimposed on natural geologic backgrounds. Mercury is found in muscle of fish from Arctic freshwaters at concentrations up to about 0.5 ppm. Radionuclides are also widespread at levels below those acceptable in food, with some local elevations near former mines. The implications of these contaminants for the northern ecosystems and the people dependent upon them are still not clear. Preliminary studies of inducible enzymes in fish suggest that the thresholds for biological damage have not been reached. PMID- 1514105 TI - Inuit foods and diet: a preliminary assessment of benefits and risks. AB - Traditional Inuit foods are contaminated with chemical residues from industrial and other activities around the world. The intake of polychlorinated biphenyls (PCBs) and polychlorinated camphenes (PCCs) exceeds the 'tolerable daily intake' (TDI) for many consumers. The implications of long term contaminant intake, even for single contaminants, are not known and will be difficult or impossible to determine in the foreseeable future. Traditional foods form a substantial part of the Inuit diet and are a major source of energy and essential nutrients. Available alternative imported foods are nutritionally inferior and substitution may lead to nutritional deficiencies and associated risks to health and to the social and cultural life of Arctic communities. PMID- 1514106 TI - Arctic marine ecosystem contamination. AB - The current state of knowledge of levels, spatial and temporal trends of contaminants in the Arctic marine ecosystem varies greatly among pollutants and among environmental compartments. Levels of polychlorinated biphenyls (PCBs), organochlorine (OC) pesticides and some heavy metals such as mercury and lead, in Arctic marine mammals and fish are relatively well documented because of the need for comparisons with biota in more polluted environments and interest in the contamination of native diets. Levels of heavy metals, alkanes, polyaromatic hydrocarbons (PAH) and OCs in the Arctic Ocean are comparable to uncontaminated ocean waters in the mid-latitudes. But concentrations of alpha- and gamma hexachlorocyclohexane (HCHs) are higher in northern waters far removed from local sources, possibly because lower water temperature reduces transfer to the atmosphere. Bioaccumulation of OCs and heavy metals in Arctic marine food chains begins with epontic ice algae or phytoplankton in surface waters. Polychlorinated camphenes (PCC), PCBs, DDT- and chlordane-related compounds are the major OCs in marine fish, mammals and seabirds. Mean concentrations of most PCBs and OC pesticides in ringed seal (Phoca hispida) and polar bear (Ursus maritimus) populations in the Canadian Arctic are quite similar indicating a uniform geographic distribution of contamination, although alpha-HCH showed a distinct latitudinal gradient in bears due to higher levels in zones influenced by continental runoff. Ringed seals from Spitzbergen have higher levels of PCBs, total DDT and polychlorinated dioxins/furans (PCDD/PCDFs). In contrast to other OCs, PCDD/PCDFs in Canadian Arctic ringed seals and polar bears were higher in the east/central Arctic than at more southerly locations. Remarkably high cadmium levels are found in kidney and liver of narwhal (Monodons monoceros) from western Baffin Bay (mean of 63.5 micrograms g-1) and western Greenland waters (median of 39.5 micrograms g-1). Mercury concentrations in muscle of ringed seal and cetaceans frequently exceed 0.5 microgram g-1 especially in older animals. Cadmium concentrations in polar bear liver increased from west to east, while mercury levels were higher in ringed seals from the western Canadian Arctic, which suggests that natural sources of these metals predominate. Studies of temporal trends in OCs in ringed seals and seabirds in the Canadian Arctic indicate PCB and DDT levels declined significantly from the early 1970s to the 1980s. There is a lack of temporal trend data for other OC pesticides as well as for heavy metals and hydrocarbons.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1514107 TI - Fibronectin: role in respiratory distress syndrome and bronchopulmonary dysplasia. AB - Further investigation is required to delineate the biochemical and cellular interactions that influence lung injury and fibrosis. The results from studies in adults, neonates, and animals suggest that fibronectin may play a key role in the development of pulmonary fibrosis following acute lung injury. Fibronectin as well as other pulmonary cytokines are essential participants in efficient and orderly wound repair; however, the excessive production of these mediators may result in an exaggeration of the normal healing process with the eventual outcome of pulmonary fibrosis. The potential role of fibronectin and other cytokines as mediators and markers of BPD may thus allow for earlier detection and identification of those infants with RDS who are at greatest risk to develop BPD, as well as aiding in the development and selection of therapeutic interventions that can more effectively treat and possibly prevent the deleterious consequences of bronchopulmonary dysplasia. PMID- 1514108 TI - Retinol (vitamin A) and riboflavin (vitamin B2) administration and metabolism in very low birth weight infants. AB - The combination of marginal hepatic retinol stores at delivery and the reduction of daily retinol dose due to complications with the delivery system places the VLBW infant receiving parenteral nutrition at high risk for retinol deficiency during the first month of life. This has serious health implications because retinol is essential during this period for normal growth and repair of the pulmonary tissue in VLBW infants. Enterally fed VLBW infants, on the other hand, receive relatively higher doses of retinol from vitamin-supplemented premature infant formula and fortified breast milk. Equally serious is the problem of monitoring vitamin A status in infants receiving supplemental doses of vitamin A. It seems clear that while plasma vitamin A levels are the most easily available method of monitoring vitamin A status, further studies are necessary to determine if these levels correlate with hepatic content. This is of particular concern since liver disease is common in VLBW infants and vitamin A hepatotoxicity has been described in a cohort of 41 patients receiving therapeutic doses of the vitamin. While further research of daily enteral and parenteral retinol requirements of VLBW infants should continue, formulation of a specific VLBW parenteral vitamin supplement should also be developed. PMID- 1514109 TI - Pulmonary functional residual capacity and lung mechanics in surfactant-treated infants. PMID- 1514110 TI - Studies of bilirubin toxicity at the synaptosome and cellular levels. PMID- 1514111 TI - The effect of endothelin-1 on the cerebrovascular response to hypoxia and hypercapnia in the newborn. PMID- 1514112 TI - Liposome-mediated transfer of fusion genes to the intact lung. PMID- 1514113 TI - Seasonality of first coitus in the United States. AB - Recent attention to causes of seasonality of births leads to an interest in seasonality patterns in the antecedents to birth, including gestational length, conception, and coital activity. In this paper we study the beginning of the process: first intercourse among adolescents and young adults. Analysis of a small and local dataset is suggestive that loss of virginity is particularly likely during the summer. A test of this "Summer Vacation Theory" using a large national dataset supports the generality of the phenomenon. Further, a prediction that seasonality patterns will change during the transition from high school to work and college is tested and supported. The existence of both biological and psycho-social mechanisms is suggested. Policy implications are reviewed. PMID- 1514114 TI - Female education, age, parity, and reproduction cessation in Ghana. AB - Data from the 1988 Ghana Demographic and Health Survey is employed to determine the existence of a relationship between the amount of education a woman has and her intent to cease childbearing. The findings are that with increasing levels of education, a female's desire to cease reproduction also increases. However, this relationship is obscured if parity is not controlled. PMID- 1514115 TI - Education and timing of parenthood among Canadian women: a cohort analysis. AB - This research examines factors associated with the timing of first birth in Canada, focusing primarily on the role of women's educational attainment. Proportional hazards modelling techniques are applied to data from the 1984 Canadian Fertility Survey (CFS) in order to determine how educational attainment, estimated as close as possible to the date of first birth, influences the timing of first birth and whether the importance of this variable varies according to age cohorts. The results suggest that among a number of variables useful for distinguishing different levels of risk, educational attainment proves to be the most important predictor in the model. Education exerts a substantial positive influence on birth timing for women of all age groups. As expected, moreover, significant cohort differences are also evident, with the greatest to the smallest impact on the risk from the youngest to the oldest cohorts. These clear cut cohort differences indicate a fundamental change in the effects of education over time, a trend most likely resulting from substantial changes in both the content and social significance of formal schooling during the past few decades. PMID- 1514116 TI - Achievement of reproductive intentions in Sri Lanka, 1982-1985: a longitudinal study. AB - The achievement or reproductive intentions of Sri Lankan women was examined by using longitudinal data for the period 1982-85. Aggregate consistency between reproductive intentions and behavior was almost perfect, but at the individual level there were inconsistencies. Among those who wanted to have no more children, 23 per cent reported a birth in the intersurvey period of 3 years and 2 months, while failures to have a wanted birth stood at 36 per cent. There was a clear declining trend in the former type of inconsistencies in Sri Lanka, but the latter type has increased, possibly due to a continuing decline in family size ideals or due to deferred childbearing. Even though inconsistencies existed, expressed fertility intentions in 1982 significantly influenced the fertility outcome. The study also has a methodological focus on whether to include sterilized women when fertility intentions and behavior are examined longitudinally, but no specific problems were found with their inclusion. Results indicate that, apart from the intention variable, age, marital duration, family size, and education of husband and wife variables all influenced fertility in the follow-up period. PMID- 1514117 TI - Reproductive and socioeconomic determinants of child survival: confounded, interactive, and age-dependent effects. AB - Studies of infant and child mortality have evolved to distinguish between two sets of explanatory variables-factors related to reproductive or maternal characteristics and socioeconomic factors, generally described as characteristics of the family or household. Almost all multivariate analyses include variables from each of these two sets, but there has been little consideration of the relationship between them. We examine how these two sets of variables jointly affect mortality. We test first for confounded effects by examining socioeconomic effects while excluding and then including reproductive variables in nested multivariate models. Next, we look for age-dependent effects among the explanatory variables and find that reproductive and socioeconomic factors affect mortality at differing ages of children. Finally, we examine interactive effects of the two sets of variables. We conclude that the higher mortality observed among the low status groups is not a result of greater concentration of poor reproductive patterns in those groups. Instead, higher status groups probably have more resources available for combating the negative effects of the same high risk reproductive patterns. PMID- 1514118 TI - Determinants of fertility decline in China, 1981: analysis of intermediate variables. AB - This study examines the proximate determinants of fertility in China by making use of the data collected by the One-per-Thousand Sample Fertility Survey of 1982. The results indicate that the most important inhibitor of potential fertility is deliberate control. Its contribution to fertility change has been far greater than all other proximate determinants. The marital structure of the population is also an important factor, while lactational infecundability and induced abortion are relatively unimportant. Comparative results by using data from the In-depth Fertility Survey conducted in Shanghai Municipality, Hebei and Shaanxi Provinces in April 1985 agree well in the ranking of the four intermediate factors. The findings point to successful family planning program and government population policies, which propelled the fertility transition to a substantial degree. Further research needs and policy implications of the results of the study are discussed. PMID- 1514119 TI - A note of the generalizability of assortative mating coefficients for personality. AB - While numerous studies have reported differential assortative mating coefficients for personality traits, little research has centered on cross-sample comparisons to determine their degree of generalizability. The present investigation examines the assortative mating coefficients for scales of the Minnesota Multiphasic Personality Inventory (MMPI) from five separate studies. An examination of these patterns of significant coefficients offers little support for this cross-sample generalizability. No significant correlations resulted between these studies in their coefficients, even when the unreliability of the different measures was controlled. It is concluded that there is little evidence to support statements of differential importance in assortment for personality variables beyond the sample under investigation. PMID- 1514120 TI - The fitness of human sociobiology: the future utility of four concepts in four subdisciplines. AB - Reported here are the results of a survey inquiring into the rate of acceptance of four sociobiological concepts in regard to their usefulness for future research. Included in the survey were members of four subdisciplines: animal behavior (biology), biological anthropology, cultural anthropology, and developmental psychology. Three types of institutions were included: universities, four- and five-year colleges, and community colleges. A total of 1,631 responses are reported with the degree of acceptance varying from highest to lowest as follows: biology, biological anthropology, developmental psychology, and cultural anthropology. These variations are related to the central concepts of each subdiscipline. PMID- 1514121 TI - Physical attractiveness: interpersonal and intrapersonal variability of assessments. AB - On the basis of face photographs, a team of 50 male judges assessed the physical attractiveness of 64 young women, giving them scores according to two scales (0/1 and 1-10). The attractiveness of each woman was then calculated as the mean value of assessments of all observers. The ratio of intra- to interpersonal variance of assessments was the measure of divergence of the observers' opinions (and its complement to unit was the measure of consistency). The correlation between assessments of attractiveness and measurements of the morphological features of the women was calculated as well as the correlation between the morphological features of the observers and the features of women regarded by them as the most attractive. The main conclusions are: Attractiveness is not solely a function of individual tastes. About 25 per cent of the assessments' variance can be explained by common opinion of the judges. Higher assessments of attractiveness are correlated with modal variants of morphological features of assessed women. There was no correlation between morphological features of the observers and the features of the women rated most attractive by those observers. PMID- 1514122 TI - Changes in sibling configurations for American preschool children. AB - This paper uses data drawn from the 1940 through 1980 Public Use Microdata Samples of the U.S. Census of Population to document sibling configurations from the child's perspective. Changes in four aspects of siblings are examined for five cohorts of white and black preschool-aged children: number, birth order distributions, spacing intervals, and sex composition. Changes in fertility behavior of adults in the post-war era had a profound effect on the structure of sibling systems experienced by children. Successive cohorts of preschool children show a rise in number of siblings through the early post-war years before showing sharp declines in number of siblings through the 1960's and 1970's. These shifts in size of sibling sets are reflected in changes in the proportion of each cohorts who are first born and only children, both of which have increased substantially by the 1980 cohort. The 1940 and 1980 cohorts have similar proportions of children with short intervals. However, the middle cohorts show the effects of the quickened pace of fertility with substantial proportions of children with comparatively short birth intervals. Finally, substantial shifts across cohorts in several measures of sex composition of children are observed. Most significantly, there is a marked decline in the proportion of children experiencing an opposite-sex older sibling. PMID- 1514123 TI - Organic-solvent water pollution and low birth weight in Michigan. AB - This pilot study explored the association between a measure of water pollution caused by benzene or chlorinated solvents and the incidence of low birth weights for white residents of Michigan counties. A positive relationship between water pollution by these contaminants and the per cent of low-weight births (less than 2,500 grams, or about 5.5 pounds) resulted despite controls for the incidence of teenaged childbearing, infrequent prenatal care, and mean household income from wages or salaries. Water pollution showed an association with the incidence of low birth weight that was as strong as that between low birth weight and low prenatal care. While correlation cannot prove causation, the finding suggests that impure water may impair fetal growth in Michigan. PMID- 1514124 TI - Is lactation nature's contraceptive? Data from Samoa. AB - Data from a Samoan menstruation study suggest that lactation, even intensive on demand lactation, does not inhibit menstruation or conception. This paper explores the applied and theoretical implications of continuing to accept lactation as a universally effective fertility control mechanism. Such thinking can have disastrous implications for family planning programs, and it keeps us from challenging long-held assumptions about lactation's role in population growth in early populations. PMID- 1514125 TI - Sex differences in vulnerability and maladjustment as a function of parental investment: an evolutionary approach. AB - Sex differences in aspects of mental health are examined as a function of uneven parental investment in children. Relative vulnerability is a new construct mediating the influence of parental investment on mental health. Couples (129) in three stages of the family life cycle are measured by scales for parental investment, relative vulnerability, anxiety, depression, and ten psychosomatic syndromes. Results show a path of positive correlations from the parent's sex to level of parental investment, to level of relative vulnerability, and to levels of anxiety and depression. Women invest more than men, and hence they are more vulnerable, anxious, and depressed. They reach the summit of their vulnerability while they have three young children. Relative vulnerability was found to have positive effects along with the negative ones and to affect women in different ways than it does men. Results are interpreted in terms of different parental strategies selected by evolution for each sex. PMID- 1514126 TI - Violent and accidental mortality among four immigrant groups in Canada, 1970 1972. AB - For most people immigration to a new country such as Canada entails a positive move and an improvement in life. The many challenges associated with resettlement may, however, lead to insurmountable difficulties, stresses and conflict for a significant number of newcomers. The mortality experience of immigrants, as reflected in cause-of-death statistics, may provide indication of the extent of stress and conflict in their migration experience. This situation is most clearly exhibited in mortality from suicide, homicide, and motor vehicle accidents. In this study, hypotheses concerning immigrant mortality in Canada are developed and tested with a log-linear model for rates pertaining to rare events. Overall, the results give support for the importance of country-of-origin effects in explaining suicide propensities, but not for homicide and motor vehicle accidents mortality. Income discrepancies are a significant determinant of variability in death rates overall, but discrepancies between the immigrants in this study and the Canadian-born are not of much significance. The strongest net effect on the cause-specific death rate is associated with group membership. This effect likely reflects a number of residual unmeasured sources of variation including the influence of the immigrant ethnic community as a source of social support, and the potential confounding effects of migration selectivity. PMID- 1514127 TI - Health care: privilege or entitlement? PMID- 1514128 TI - Reclaiming the community: the strengths perspective and deinstitutionalization. AB - In the past decade, concern for the plight of severely mentally ill people has centered on such issues as mental illness among the homeless population, the burden placed on families who care for ill loved ones, and the impoverished quality of life experienced by those who attempt to survive on their own. Some have called for a rethinking of the abandonment of the asylum and a relaxation of civil commitment laws, while others have advocated for increasing community-based services that specifically target severely mentally ill people. This article discusses these issues and considers how the response to severe mental illness has overrelied on pathology-based models of helping. The strengths perspective provides an alternative. Although severe mental illness presents a formidable obstacle to the afflicted, mentally challenged individuals have strengths and abilities that can be tapped to foster their continued integration in community settings. This adjustment is best conducted through the use of naturally occurring community resources rather than specialized, segregated programs. PMID- 1514129 TI - Corporate funding of human services agencies. AB - This article reviews national trends in the organization of corporate giving to human services agencies, examines how corporations make funding decisions, and reports the results of a case study of philanthropic giving among 29 companies in Cambridge, Massachusetts. The study found that most corporations use an informal rather than a formal process for making funding decisions, with many firms relying on tradition, social contacts, and intuition to guide allocations. Suggestions that social services administrators can use to enhance development planning at their agencies are provided. PMID- 1514130 TI - Enhancing the delivery of effective mental health services to children. AB - An increasing number of children and adolescents are in need of mental health services, although few children receive the treatment they need. Although progress in understanding and treating children's mental disorders is limited, a great deal more is known today about how to prevent mental disorders, what treatments are effective, and the importance of providing multiple services. This article presents current knowledge on assessment, treatment, and service delivery to help social workers improve the effectiveness of services for children. PMID- 1514131 TI - EAP's response to personal stress and productivity: implications for occupational social work. AB - Ethical and practice issues regarding the beneficiary of social work services in the workplace have been raised in the literature. However, no empirical studies could be found that specifically address these issues. This study's findings indicate that although personal stress and employee productivity are related, employee assistance program interventions improve employee productivity without reducing employee stress. Challenges and implications for occupational social work are discussed in light of the profession's person-in-environment configuration. PMID- 1514132 TI - When problems seem overwhelming: emphases in teaching, supervision, and consultation. AB - The intractability of many of today's problems creates unusual stress for social workers. Traditional direct practice content taught by teachers, field work instructors, agency supervisors, and consultants provides a sound foundation on which to teach and learn practice skills. However, it also is essential for teachers, instructors, supervisors, and consultants to recognize the unusually stressful nature of practice and the frequent sense of pervasive hopelessness felt by practitioners. This article focuses on the preparation of social workers for effective work in today's complex social environment and suggests five major areas that need to be emphasized in teaching, supervising, and training. PMID- 1514133 TI - Social workers training primary care physicians: essential psychosocial principles. AB - The growth of primary care medicine is opening new roles for the social worker in medical education to provide instruction and to design curricula that include the psychosocial dimensions of medical practice. This article describes a family oriented, community-based medical residency program in which the social work faculty plays a prominent role in the education of young physicians. The relevance of core social work principles to medicine and how they are introduced into the teaching and precepting of medical residents are discussed. PMID- 1514134 TI - Caregiver support groups: factors affecting use of services. AB - Use of time-limited psychoeducational support groups by family caregivers to help frail elderly people in the community reflects a mixture of predisposing, enabling, and need factors. Using multivariate regression methods that control for dependent-variable censoring, the authors found that attendance in support groups by primary caregivers was greater for those who were older, who had a secondary informal caregiver involved in providing care, or who had significant health problems. Attendance was greater also for those caring for Alzheimer's victims and for those experiencing higher levels of burden in their caregiving role. In English-language groups, Mexican American caregivers showed markedly lower attendance than Anglo American caregivers, but in Spanish-language groups attendance by Mexican American caregivers was essentially the same as that of the Anglo Americans in English-language groups. Data for this study are from a federally funded support group demonstration project conducted in a southwestern metropolitan area. PMID- 1514135 TI - What is reform in health care? PMID- 1514136 TI - [Granulocyte alkaline phosphatase activity in the chronic phase and blastic crisis of chronic myeloid leukemia. Sequential study of 43 patients]. AB - PURPOSE: To evaluate in a sequential fashion the activity of the leukocyte alkaline phosphatase (LAP) in the chronic phase and the blastic crisis of chronic myelogenous leukaemia (CML). MATERIAL AND METHODS: This study is comprised of 43 patients diagnosed of CML according to standard criteria. The initial LAP scores were compared with those recorded in the blastic crisis, using cytochemical methods. The statistical analysis was performed with Student's test and chi square. RESULTS: The LAP activity at diagnosis was low in 40 of the 43 cases (93%), the score being 0 in 20 instances. In the blastic crisis low scores were found in 27 patients (63%), while LAP activity appeared normal or increased in 16 others (37%). When the LAP scores of the two phases of the disease were compared the differences were found statistically significant (p less than 0.0001 and p less than 0.0007, respectively). CONCLUSIONS: These results confirm that the onset of the blastic crisis of CML is often accompanied by an increase of the LAP activity, although this last persists low in the majority of the patients. PMID- 1514137 TI - [Low-grade non-Hodgkin's lymphomas. Study of 73 cases]. AB - PURPOSE: To analyse the clinico-biologic features at diagnosis and the response to therapy and survival of a group of patients with low-grade non-Hodgkin's lymphoma (NHL). MATERIAL AND METHODS: The study comprises 73 NHL patients diagnosed between 1974 and 1989 in the Covadonga Hospital and classified as low grade in accordance with the international Working Formulation. The first-line treatment regimens used were cyclophosphamide-vincristine-prednisone (CVP), chlorambucil-prednisone (CBL-PRED), radiotherapy, and other combinations. The statistical study was performed by comparative statistics (Student's tests, chi square), univariate analysis (Cox Mantel method) and multivariate analysis (Cox proportional risks); the BMDP pack was used for the study. RESULTS: The median age of the group was 63 years. Stages III and IV were seen at first in 75% of the patients, and 22% of the series had extranodal involvement. CVP was used in 69% of the cases, 7.6 received CBL-PRED, 11% were given radiotherapy, and other combinations were given to 11% of the patients. As a whole, responses were seen in 46 cases (73%), of whom complete remission (CR) was achieved in 49% and partial remission (PR) or minor responses (MR) were attained in 24% of instances. The factors influencing upon CR were: stage (p less than 0.0005), B-symptoms (p 0.004), splenomegaly (p less than 0.801), platelet count and haemoglobin rate (p less than 0.01). The total survival at 10 years was 53%, and the disease-free survival for those attaining CR was 48%, with disease-free median of 81 months. The univariate analysis was influenced in a negative fashion by the following: peripheral blood lymphocyte count below 2 x 10(9)/L, B-symptoms (p less than 0.002), bulky tumoural mass (p less than 0.007), advanced stage (p less than 0.003) and, chiefly, response to treatment (p less than 0.0001). The 10-year survival of the patients achieving CR was 86%, that of both types of response (PR and MR) was 20%, and it was 0% for the failures. CONCLUSIONS: 1) Patients in low stages have high possibilities of curation with radiotherapy. 2) CVP for advanced stages provides moderate percentage of response, with CR rate lower than 50%. It is necessary to select those patients with unfavourable prognostic factors in order to use aggressive treatment to achieve CR. 3) Patients attaining CR have better prognosis in spite of the frequent relapses (63% at 10 years). PMID- 1514138 TI - [Plasma cell leukemia. Study of 6 patients]. AB - PURPOSE: To analyse the clinico-biological characteristics, the clinical course and the response to therapy in a group of patients with plasma cell leukaemia (PCL). MATERIAL AND METHODS: Out of a total number of 107 patients diagnosed of multiple myeloma (MM) between 1983 and 1991, 6 were found to meet the criteria for PCL (prevalence: 5.6%). This was primary in 2 cases and secondary in the remaining 4. The M/F ratio was 2/1 and the median age was 63 years (range: 57-69 years). RESULTS: Two patients had bone pain and two others weight loss at the onset of PCL. The outstanding haematological findings were increased ESR, normocytic-normochromic anaemia and thrombocytopenia, which were present in all cases. The percentage of peripheral blood plasma cells was between 29 and 70, and the bone marrow aspirate showed plasma cell infiltration over 40% in all cases. Serum M component was found in 5 patients, with decreased values of the polyclonal immunoglobulins; the remaining patient had non-secretory MM. Renal insufficiency was present in 3 patients at diagnosis. Three of the 4 patients with secondary PCL had been previously given combination chemotherapy and the remainder had received melphalan and prednisone. The period between the diagnosis of MM and the development of PCL ranged between 1 and 21 months (median 15 months). Three patients were treated with the M-2 protocol and the others received only supportive therapy. Transient partial response could be achieved in only one case with chemotherapy. All the patients have died, the actuarial survival median being 1 month (range, 1-7 months). Three patients died of infection, 2 of renal insufficiency and one of heart failure after acute myocardial infarction. CONCLUSION: The poor prognosis of PCL was confirmed, along with the scarce response to therapy of these patients. PMID- 1514139 TI - [Thrombin-antithrombin complexes and F1+2 prothrombin fragment in coronary revascularization surgery. Relationship with graft occlusion]. AB - PURPOSE: To evaluate the possible role played by activation of the coagulation system in the early occlusion of grafts in patients subjected to aortocoronary bypass. PATIENTS AND METHODS: This study includes 30 patients subjected to coronary revascularization surgery. The plasma rates of thrombin-anti-thrombin complexes (TAT) and 1+2 prothrombin fragments (F1+2) were measured before and after surgery. The studies were performed by enzyme immunoassay techniques. Selective angiography was performed in every patient on the 10th day after surgery. Descriptive statistics, Student's t test and Mann-Whitney U test were used for comparison of means ans statistical analysis. RESULTS: Occlusive lesion was shown by angiography in 15 of the 30 patients. The TAT and F1+2 levels showed a statistically significant increase (p less than 0.001) along the postoperative period, without any correlation regarding the presence or absence of occlusion. The preoperative concentration of TAT was significantly higher in patients with thrombotic occlusion (p less than 0.05). CONCLUSIONS: 1) Marked activation of the coagulation system is present in patients subjected to coronary revascularization surgery. 2) The pre-operative determination of TAT may be of value for predicting early graft occlusion. PMID- 1514140 TI - [Autoimmune hemolytic anemia. Review of 200 cases studied in a period of 20 years (1970-1989)]. AB - PURPOSE: To propose a new aetiologic classification of the patients suffering from autoimmune haemolytic anaemia (AIHA). MATERIAL AND METHODS: Two-hundred cases of AIHA studied and followed-up between 1970 and 1989 are presented. From an aetiological and pathogenetic standpoint the disease was classified into 4 groups: (1) idiopathic, (2) secondary, (3) associated and (4) accompanying. RESULTS: The percentage of the different AIHA types, in accordance with the antibodies behaviour, was: (1) warm-reacting AIHA, 74.5%; (2) cold-reacting, 19%; (3) combined or mixed pattern, 6.5%. The immunoglobulins fixed on red cell surface and the specificity of the antibodies found corresponded to those reported in the literature. No treatment was needed in 27.5% of the cases. Corticosteroids were the therapy used in virtually all the cases. Corticosteroids were favourable effect could be appreciated in about 80% of the patients treated. Splenectomy had to be performed in 13.1% of the patients; 47.4% of them attained complete remission while 56.2 failed to respond. Nonsteroid immunosuppressive agents were used in 16.5% of the cases, with 50% of total or partial responses. There are striking prognostic-evolutive differences when this study is viewed from the patients or the AIHA standpoints. Thus, the mortality reached 57.5% of the cases, but in only 10% it was related with AIHA, and something similar could be said about remissions. CONCLUSIONS: The analysis of this series allows one to establish: (1) four aetiopathogenetic groups of AIHA; (2) a high percentage of cases related with severe underlying diseases; (3) over 50% incidence in people over 50 years of age, and (4) natural ageing of the series is appreciated after a long follow-up (1-20 years). PMID- 1514141 TI - [Analysis of DNA polymorphism for paternity determination and follow-up of bone marrow transplants]. PMID- 1514142 TI - [Physiopathologic focus of the treatment of consumption coagulopathy in acute non lymphoblastic leukemia]. PMID- 1514143 TI - [Parahemophilia. Study in a family of 3 generations]. AB - Three generations of a family with congenital deficit of factor V are reported. Those subjects showing symptoms were heterozygous. The transmission of the disease appears to be autosomal recessive. From a clinical standpoint, the patients suffered moderate haemorrhages, mostly affecting mucosae, which became severe on occasions, chiefly after labour. Isolated factor V rates did not correlate with the severity of bleeding. The different variants reported in the literature are commented. Transfusion of fresh-frozen plasma seems and adequate therapeutical approach for this disorder. PMID- 1514144 TI - [Non-Hodgkin's lymphoma associated with human immunodeficiency virus infection in children]. AB - A 3-year-old boy with infection by the human immunodeficiency virus (HIV) developed stage IV Burkitt's lymphoma. Complete remission was achieved with the BFM-86 protocol. One month after finishing treatment, and still in complete remission, fever appeared and seropositivity to HIV was found. The child was diagnosed of AIDS (P2-E1) and died 10 days later. Although the association of HIV infection and Burkitt's lymphoma is well known in adults, it is extremely rare in children. The routine HIV screening is suggested for children with non-Hodgkin's lymphoma. PMID- 1514145 TI - [Resistance to antivitamins K]. AB - Resistance to oral anticoagulant is a rare phenomenon. We report the case of a 32 year-old woman who required anticoagulation due to a deep venous thrombosis. She gradually developed resistance to acenocumarol and warfarin. Although the HPLC (high performance liquid chromatography) method proved satisfactory acenocumarol levels in plasma, therapeutic anticoagulation was not achieved. The mechanisms of resistance are discussed. PMID- 1514146 TI - [Thrombocytosis in a Ph1 positive chronic myeloproliferative syndrome. Chronic myeloid leukemia or essential thrombocythemia]. PMID- 1514147 TI - [Association of elliptocytosis and beta-thalassaemia: report of a case and family study]. PMID- 1514148 TI - [Primary non-Hodgkin's lymphoma of the ovary. Report of a case]. PMID- 1514149 TI - [Acute lymphoblastic leukemia as a second neoplasia in Hodgkin's disease]. PMID- 1514150 TI - [Non-Hodgkin's lymphoma in a patient with ataxia telangiectasia]. PMID- 1514151 TI - [With regard to a double factor XI/XII deficiency]. PMID- 1514152 TI - Further appraisal of APACHE II limitations and potential. AB - Hemodynamically unstable patients selected for invasive cardiovascular monitoring were divided into APACHE II subgroups for risk stratification to study interrelationships among monitoring, therapy, resulting cardiovascular function and outcome. When compared by regression analysis, there were no clinically relevant relationships between APACHE II scores and total intervention points (r2 = 0.02), days of invasive monitoring (r2 = 0.000001), initial cardiovascular function (r2 = 0.069) and final cardiovascular function (r2 = 0.05). Analysis of variance (ANOVA) was done between APACHE subgroups and total points (zero of 20 intragroup comparisons were different by the Scheffe test; p = 0.33), days of monitoring (zero of 20 were different; p = 0.61), initial cardiovascular function (three of 20 comparisons were different; p = 0.003) and final cardiovascular function (zero of 20 were different; p = 0.24). Opposite relationships in patients who lived and died were noted between total intervention points and APACHE II subgroups (p = 0.028, two-way ANOVA). There was an increasing number of total intervention points in patients who ultimately lived in ascending initial APACHE II subgroups. In contrast, there was a decreasing number of total intervention points in patients who ultimately died in the same APACHE II subgroups. APACHE II stratification failed to help understand the relationships among clinically important parameters. At the same time, while APACHE scores are claimed to be independent of therapy, the score seemed to be extremely sensitive to interventions, especially important in surgical populations. Should the APACHE II scores remain high in the face of continued maximal intervention, fatal outcome can be predicted. This pattern is remarkably similar across the entire initial APACHE spectrum. The predicated attributes of APACHE II scores, that is, risk stratification and independence from therapy, are neither necessary or desirable. Understanding patterns that are associated with survival or death may require alternative mathematic approaches, such as group and set theory manipulated by principles of Boolean algebra. New approaches may be more fruitful than further attempts to refine existing systems. PMID- 1514154 TI - Avoiding complications and decreasing costs of central venous catheter placement utilizing electrocardiographic guidance. AB - A technique for electrocardiographic (ECG) guided percutaneous placement of central venous catheters (CVC) was studied in a prospective, randomized manner. In 34 patients, 51 ECG guided percutaneous CVC were compared with 29 blind percutaneous CVC in 23 patients. Thirty-nine percent of CVC placements were changes over a guide wire. Ideal catheter tip location at the atriocaval junction was achieved in 96 percent of the patients in the study versus 59 percent of those in the control group (p less than 0.001). In addition, we report 25 patients with open placement of CVC using intraoperative ECG guidance and fluoroscopic confirmation. Ideal location of the catheter tip was achieved in 100 percent of these patients. ECG guided CVC placement using the technique described herein obviates the need for catheter repositioning, repeat roentgenographic studies and intraoperative fluoroscopic imaging, along with the attendant costs and radiation exposure to staff and patient. Aberrant catheter tip placement and the associated morbidity are also eliminated. PMID- 1514153 TI - Combined liver and whole pancreas procurement in donors with a replaced right hepatic artery. AB - Aberrant donor arterial anatomy, such as a replaced right hepatic artery, is often considered a contraindication to combined liver and whole pancreas procurement for transplantation. With the increasing interest in transplantation of the pancreas and the demand for cadaver organs, methods for simultaneous procurement despite aberrant donor anatomy are essential. We describe the surgical techniques used successfully in six instances of combined liver and whole pancreas procurement in donors with a replaced right hepatic artery and suggest that a replaced right hepatic artery should not preclude simultaneous procurement in otherwise suitable donors. PMID- 1514155 TI - Enhancement of true-positive rates for nonpalpable carcinoma of the breast through mammographic selection. AB - A retrospective review of 332 needle localization biopsies for nonpalpable mammographic abnormalities was performed. Twenty-one invasive and 12 noninvasive carcinomas were identified in this population, for a true positive biopsy rate of 10 percent. A review of all needle localization mammograms performed on these patients by a radiologist specializing in mammography identified 225 mammograms with a low probability of malignancy. In this group, there were four in situ and six invasive carcinomas (true positive biopsy rate of 4 percent). In the remaining 107 mammograms with a high probability of malignancy, there were eight in situ and 15 invasive carcinomas (true positive biopsy rate of 21.4 percent). In the low probability group, fine needle aspiration or excisional biopsy were recommended for six of the ten neoplasms and follow-up mammograms at three to six months for the remaining four (two in situ and two invasive carcinomas). Using selectivity, 225 biopsies could have been avoided at a savings of $97,368 (Canadian dollars) in fees for physicians alone while still identifying 29 of 33 neoplasms (87 percent of all neoplasms) and possibly delaying diagnosis for three to six months or longer in four of 33 neoplasms (13 percent, two in situ and two invasive) for which follow-up mammograms were recommended. PMID- 1514156 TI - The results of autopsy of patients with surgical diseases of the digestive tract. AB - The results of autopsy of 77 patients who died because of surgical disease of the digestive tract were compared with antemortem findings. An analysis was performed to identify missed diagnoses and incorrect therapy. Primary diagnoses had not been frequently missed, but many complications of the primary disorder or treatment had been overlooked. Many patients died because of septic conditions. Error in treatment, with an adverse impact on the course of the disease as assessed by the postmortem examination, occurred in 9 percent of the patients. The most common error had been failure to reoperate upon patients with an intra abdominal complication. Unexpected death was significantly associated with incorrect diagnosis; failed or inadequate diagnostic methods were significantly associated with treatment failure (chi-square tests). The autopsy remains a valuable procedure in clinical operation. Selection of patients for autopsy, as indicated by decreasing autopsy rates, is not justified. PMID- 1514157 TI - Surgical management and prevention of vaginal vault prolapse. AB - From 1984 to 1988, we corrected and prevented the prolapse of the vaginal vault of patients who wanted to maintain a satisfactory sexual function. This was done by adopting two different surgical techniques. The first, generally favored technique, was performed upon 179 patients and consisted of a colposuspension to the sacrospinous ligaments. The second technique, a colposacropexis, was performed upon 71 patients, in which abdominal associated pathologic changes required an abdominal surgical approach. Colposacropexis was performed, whenever possible, directly to the anterior longitudinal vertebral ligament or using synthetic materials (Mersilene [polyester fiber], Teflon [polytetrafluoroethylene] and Gore-Tex [expanded, reinforced polytetrafluoroethylene]). Both colposacropexis and vaginal suspension to sacrospinous ligaments have had comparable results in vaginal accommodation and long term fixation. Vaginal approach has a lower incidence of operative complications than the abdominal approach and seems to ensure a lower risk of recurrent cystocele, even if simple and asymptomatic. PMID- 1514158 TI - Surgical treatment for cholelithiasis. AB - In a retrospective study, the results of 1,631 consecutive operations for cholelithiasis were analyzed. With an overall mortality rate of 0.18 percent and a reoperation rate of 1.3 percent, conventional cholecystectomy proved to be a safe method. Mortality proved to be age dependent, with a zero mortality rate for patients less than 60 years of age. Choledochotomy had a 13-fold greater mortality rate than simple cholecystectomy (0.92 versus 0.07 percent). For acute cholecystitis, we observed an unusual zero mortality rate, whereas the mortality rate in chronic cholecystitis was 0.2 percent. All three patients who died had an accompanying cirrhosis of the liver. Morbidity, defined as reoperation during the same period of hospitalization, was mainly the result of retained stones after choledochotomy; endoscopic papillotomy was the treatment of choice. Cholecystectomy remains the "gold standard" in the treatment of cholelithiasis. PMID- 1514159 TI - Poor predictive value of hematocrit and hemodynamic parameters for erythrocyte deficits after extensive elective vascular operations. AB - Fluid resuscitation and transfusion therapy are particularly critical in patients undergoing extensive vascular operations because of diffuse atherosclerosis and the risk of perioperative myocardial infarction. Sophisticated perioperative monitoring has reduced the mortality rate substantially, but indications for transfusion remain controversial. We determined erythrocyte volume, (EV), total blood volume (TBV) and plasma volume (PV) preoperatively and 18 to 24 hours postoperatively in 41 elderly patients (68.8 +/- 1.3 years) undergoing elective vascular operations (30 abdominal aortic aneurysmorrhaphy, ten aortofemoral bypass and one carotid endarterectomy). EV was measured using 51chromium-labeled autologous erythrocytes; TBV and PV were calculated from EV and total body hematocrit (peripheral venous hematocrit [HCT] x 0.89). Ideal blood volumes were calculated from nomograms based on body surface area and gender. Relationships between body volumes (percentage of ideal), simultaneously measured peripheral venous HCT and hemodynamic parameters heart rate, mean arterial pressure, central venous pressure, pulmonary capillary wedge pressure, cardiac index and systemic vascular resistance index were studied by stepwise regression. In 24 patients, blood volumes and hemodynamic parameters were also measured in the recovery room. HCT significantly correlated with EV at all three time periods (p less than 0.001), but the ability of HCT to predict EV in an individual patient was relatively poor (r = 0.50 preoperatively; r = 0.54 in recovery room and r = 0.66 24 hour postoperatively). By 24 hours postoperatively, EV had decreased to 78.3 +/- 2.4 percent of ideal EV (range of 47 to 112 percent). However, only two patients had HCT less than 30 despite the fact that 13 of 41 patients had an EV deficit of greater than 30 percent. No patient had a HCT of less than 25 percent. Hemodynamic parameters did not contribute to the prediction of EV, PV or TBV at any time. Two patients had myocardial infarctions postoperatively associated with 24 hour EV deficits of 18.5 and 29.6 percent. One patient died of a pulmonary embolus. Because of these findings, the concept of a "transfusion trigger" must be viewed with caution, since many patients undergoing vascular operations will have considerable EV deficits despite an "acceptable" HCT. PMID- 1514160 TI - Role of three hour roentgenogram of the chest in penetrating and nonpenetrating injuries of the chest. AB - The current study examined whether a three hour roentgenogram of the chest was as reliable as the six hour roentgenogram of the chest in detecting delayed complications (that is, pneumothorax and hemothorax) of penetrating and nonpenetrating trauma to the chest. The 285 patients in the study were placed into three groups: those stabbed in either the chest or back; those sustaining multiple fractures of the ribs, and those with gunshot wounds to the chest or back. All the patients selected for study by three and six hour films of the chest were asymptomatic on admission and no pneumothorax or hemothorax was seen on initial anteroposterior and lateral roentgenograms of the chest. None of the patients included in the study required immediate operation. Twelve patients (4 percent) had delayed pneumothoraces on the three hour roentgenogram of the chest. Nine of these 12 (75 percent) required thoracostomy tube drainage, while the remaining three patients were managed with needle aspiration. No additional patients had complications on the six hour roentgenogram of the chest. Computed tomographic (CT) scan discovered five additional patients (2 percent) with pneumothoraces not visualized by the three or six hour films. Seventeen patients (6 percent) had delayed pneumothoraces despite negative admission roentgenograms of the chest and lack of symptoms. Twelve of the 17 (71 percent) were discovered on three hour roentgenogram of the chest, while an additional five of 17 (29 percent) were only seen by CT scan. Three hour roentgenograms of the chest are as reliable as six hour roentgenograms of the chest in visualizing the development of delayed complications of penetrating and nonpenetrating thoracic trauma. The CT scan is more effective than the roentgenogram of the chest in visualizing small pneumothoraces, but its use as a screening tool for detection of delayed complications of trauma to the chest pneumothoraces is probably cost-prohibitive. PMID- 1514161 TI - Factors influencing the outcome of a no incision endoscopic urethropexy. AB - A urethropexy without incision has been used in 108 women with a minimum of one year follow-up evaluation. Most of the patients (81 percent) experienced postoperative urinary retention, with the mean period of retention being 22 days. The cure rate was 81.5 percent. The technique was successful in women with grade I stress urinary incontinence (97 percent), but not as effective in women with high grade stress incontinence (45.5 percent in women with grade III stress urinary incontinence). The success rate, therefore, correlated significantly with the grade of incontinence (p less than 0.001). It is noteworthy that there were no failures in 36 women who were premenopausal and the cure rate of 72 percent in the postmenopausal group represented a significant reduction (p less than 0.001). The approach without incision is often effective in patients who have failed previous anti-incontinence procedures, with a cure rate of 82 percent in 22 women in this category, but most patients with a successful outcome in the more complex instances of stress urinary incontinence were also noted to be premenopausal. These data suggest that the success of the repair is dependent on the strength and integrity of the vaginal mucosa. When using the no incision technique, it is advisable to avoid the use of foreign body material in the suprapubic stab sites because of the high incidence of infection and tender nodules. PMID- 1514162 TI - Surgical curability and prognosis for standard versus extended resection for T1 carcinoma of the pancreas. AB - The prognosis of 185 patients who underwent surgical resection of small carcinomas of less than 2.0 centimeters (T1) of the pancreas in whom either standard or extended resection was used was analyzed. Pancreatic resection was performed upon 98.3 percent of the patients who were more than 49 years old. The location of the tumor was the head of the pancreas in 83.4 percent of the patients, the body of the pancreas in 13.2 percent and the tail of the pancreas in 3.3 percent. Tumor staging revealed 42.9 percent in stage I and the remainder in advanced stage, that is 33.1 percent stage II, 18.8 percent stage III and 5.1 percent stage IV. When standard resection was performed, surgical cure rates were more than 80 percent in stage I, II and III, but in stage IV, it was only 16.6 percent. After extended resection, the surgical cure rates increased even in stage IV (100 percent). There were no significant differences in the overall postoperative cumulative survival rates between standard and extended operation. In stage II, however, a significant better survival rate was observed after extended resection than after standard resection. PMID- 1514163 TI - A new technique of side to side caval anastomosis during orthotopic hepatic transplantation without inferior vena caval occlusion. AB - An original technique of OLT with preservation of the entire IVC of the recipient and side to side caval anastomosis is described. The procedure has permitted the avoidance of retrocaval dissection and temporary vena caval occlusion. The caval outflow was respected during the anhepatic phase. The technique, requiring only one caval anastomosis, has reduced the duration of the anhepatic phase and the need for venous bypass. PMID- 1514165 TI - The bacterial factor in hemorrhagic shock. AB - After a century of research on hemorrhagic shock, traumatic shock, septic shock and burn shock, it is known that all of the states lead to cellular injury and death through the same common pathways. Methods for blocking these pathways may ameliorate all of these conditions. PMID- 1514164 TI - Nutritional support for acute pancreatitis. AB - The current review has summarized current data relevant to the nutritional support of patients with acute pancreatitis. Selection of the most appropriate form of nutritional support for patients with acute pancreatitis is intimately linked to a thorough understanding of the effects of various forms of enteral and parenteral nutrition on physiologic exocrine secretory mechanisms. Two basic concepts have emerged from the multiple studies that have addressed these issues to date: 1, enteral feeds should have low fat composition and be delivered distal to the ligament of Treitz to minimize exocrine pancreatic secretion and 2, parenteral substrate infusions, alone or in combinations similar to those administered during TPN, do not stimulate exocrine pancreatic secretion. From a practical standpoint, most patients with acute pancreatitis are diagnosed by nonoperative means and will manifest some degree of paralytic ileus during the early phase of the disease. Therefore, jejunal feeds are usually not a therapeutic option early in the course of this disease. On the basis of the clinical studies reviewed herein we propose general guidelines for the nutritional support of patients with acute pancreatitis: 1, most patients with mild uncomplicated pancreatitis (one to two prognostic signs) do not benefit from nutritional support; 2, nutritional support should begin early in the course of patients with moderate to severe disease (as soon as hemodynamic and cardiorespiratory stability permit); 3, initial nutritional support should be through the parenteral route and include fat emulsion in amounts sufficient to prevent essential fatty acid deficiency (no objective data exist to recommend specific amino acid formulations); 4, patients requiring operation for diagnosis or complications of the disease should have a feeding jejunostomy placed at the time of operation for subsequent enteral nutrition using a low fat formula, such as Precision HN (Sandoz, 1.3 percent calories as fat), Criticare HN (Mead Johnson, 3 percent calories as fat) or Vivonex High Nitrogen (Norwich Eaton, 0.87 percent calories as fat), and 5, oral feedings should be low fat in composition and should be reinstituted using traditional clinical criteria, including the symptoms of the patient, physical examination and computed tomographic appearance of the pancreas (clinicians should bear in mind the well documented exocrine stimulatory effects of even low fat oral feeds and the risks of early refeeding). These general guidelines must be individualized to incorporate what is perhaps the most important clinical variable--the premorbid nutritional state of the patient.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1514166 TI - Extra-cranial bleeding and other symptoms due to low dose aspirin and low intensity oral anticoagulation. AB - Data from the early stages of the thrombosis prevention trial (TPT) have been used to establish and quantify the risk of extracranial bleeding due to low dose aspirin (75 mg) and low intensity oral anticoagulation with warfarin (international normalised ratio, INR, 1.5) singly or in combination, in men aged between 45 and 69 who are at high risk of ischaemic heart disease (IHD). The design of the trial is factorial, the four treatments being combined low dose aspirin and low intensity anticoagulation (WA), low intensity anticoagulation alone (W), low dose aspirin alone (A) and double placebo treatment (P). The trial is being carried out through the Medical Research Council's General Practice Research Framework, with participating practices throughout the United Kingdom. Results are based on the first 3,667 men entered. The risk of major gastrointestinal bleeding due to active treatment is probably about 1 in 500 man years of treatment, there currently being no difference between the three active regimes (WA, W, A). Intermediate and minor bleeding episodes occur more frequently with WA than with W or A on their own, the excess being mainly due to minor nose bleeds and bruises. In turn, both W and A on their own cause more such minor episodes than placebo treatment, P. There is no evidence that any of the three active regimens increases the risk of peptic ulceration, nor do they increase reports of indigestion. Aspirin increases reports of constipation and reduces reports of blurred vision. Minor bleeding occurs less frequently in smokers than in non-smokers but is not influenced by age. The antithrombotic regimes used are feasible and acceptable. PMID- 1514167 TI - Granulocyte elastase, tumor necrosis factor-alpha and urokinase levels as prognostic markers in severe infection. AB - We have examined the prognostic value of the levels in the blood of granulocyte elastase-alpha 1-proteinase inhibitor (E-alpha 1-PI) complex, tumor necrosis factor-alpha (TNF-alpha) and urokinase-type plasminogen activator (u-PA) in 35 patients with severe infection upon admission to an Intensive Care Unit. Fourteen patients died. No differences for E-alpha 1-PI complex were found between survivors and nonsurvivors, but in all patients the levels on admission were eight-fold higher than the reference value. TNF-alpha levels, measured by immunoassay, on admission were four times higher in the nonsurvivors than in the survivors (p = 0.0003) and correlated with the severity of the disease (APACHE II score, r = 0.43, p less than 0.05). TNF-alpha was not detectable by bioassay. Total u-PA antigen (u-PA Ag), plasmin-activatable single-chain u-PA (scu-PA) and inactive, nonactivatable u-PA (u-PA#) were on admission all two-fold higher in the nonsurvivors (p = 0.0006, 0.003 and 0.0003, respectively), while normal in the survivors. In both, survivors and nonsurvivors, the ratio between scu-PA and u-PA Ag was significantly decreased (p less than 0.001, compared to a reference group of healthy volunteers), indicative for enhanced conversion of scu-PA to active two-chain u-PA (tcu-PA) and inactive u-PA# during severe infectious disease. tcu-PA was detected in nine of the 35 patients, while virtually undetectable in controls. scu-PA correlated with the Child-Pugh score on admission (r = 0.42, p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1514168 TI - Pronounced effects of the combination of a new thromboxane antagonist (GR32191) and heparin on bleeding time in man. AB - Potential pharmacokinetic and pharmacodynamic interactions between two oral doses of GR32191 (40 and 80 mg), a new thromboxane antagonist, and heparin (5,000 IU bolus + 1,000 IU/h for 3 h) were studied in eighteen healthy male volunteers using two separate double-blind, randomised, placebo-controlled, cross-over studies. Mean (range) bleeding time values were 8.4 min (7.5-9.7) during heparin/placebo, 12.1 min (9.2-18.6) (GR32191/placebo) and 16.3 min (11.5-21.4) (GR32191/heparin) in the 40 mg study, while these values were 8.7 min (5.5-15.5), 16.0 min (9.3 - greater than 36.0) and 23.8 min (10.7 - greater than 36.0), respectively in the 80 mg study. Compared to screening values, the combination of 80 mg of GR32191 and heparin had a greater effect on the bleeding time than the sum of the prolongations after the separate treatments (p = 0.05). In the 40 mg study this was not the case. Pharmacokinetics of heparin (as assessed by plasma anti-Xa and antithrombin activity) and GR32191 were unaltered during co administration of the two drugs. GR32191 did not influence the effects of heparin on APTT. Heparin slightly diminished the inhibition of collagen induced platelet aggregation by 80 mg of GR32191 and the U-46619 (thromboxane A2-mimetic) induced platelet aggregation remained unchanged. Overall fibrinolytic activity (as evaluated by the fibrin plate test) was similar during all three treatments in the study with 80 mg. The combination of 80 mg of GR32191 and heparin caused a prolongation of the bleeding time which was more than expected on the basis of their individual effects. PMID- 1514169 TI - Diurnal rhythm in anticoagulant effect of heparin during a low dose constant rate infusion. A study in healthy volunteers. AB - The objective of the study was to investigate possible diurnal rhythms in coagulation tests during a continuous intravenous infusion of unfractionated heparin. Six volunteers participated in the study, which was divided in a treatment (500 U heparin/h for 30 h) and a control experiment. Under basal conditions, no rhythm was found in coagulation tests. During heparin treatment, APTT, thrombin clotting time and anti-Xa activity showed a greater anticoagulant effect at night, with a striking decrease in the morning. In a search for the explanation of this phenomenon we looked for diurnal variations in the urinary excretion of heparin, in the plasma concentrations of antithrombin III and platelet factor 4, and in the effect of heparin added to the plasma samples in vitro. None of these studies provided the explanation. PMID- 1514170 TI - Clearance of recombinant tissue factor pathway inhibitor (TFPI) in rabbits. AB - The pharmacokinetics of recombinant tissue factor pathway inhibitor (TFPI) after an intravenous bolus injection was studied in rabbits. Clearance of TFPI was followed by measurement of the radioactivity of the 125I-labelled compound in the whole plasma or the trichloroacetic acid precipitate and by quantitation of the functional TFPI activity of the unlabelled compound using a tissue factor-induced coagulation assay. When iodinated TFPI was used, the ratios of the trichloroacetic acid precipitable counts vs. that of the whole plasma was about 1 in the first 10 min after TFPI injection, but this ratio gradually decreased to less than 0.5 after 2 h. This result suggested that the iodinated TFPI in the plasma was partially degraded after prolonged circulation in the animal. When unlabelled TFPI was used, the clearance of TFPI activity from the plasma exhibited bi-exponential elimination kinetics with a rapid alpha phase half-life (t1/2 alpha) of 2.3 min, and a terminal beta phase half-life (t1/2 beta) of 79 min. The plasma clearance was 4.2 ml kg-1 min-1. The tissue distribution of intravenously administered 125I-TFPI in the rabbit was studied using whole-body autoradiography. At 3 min after dosing, significant levels of TFPI were apparent in the liver, kidney, and other highly blood perfused tissues. Significant levels of 125I-TFPI-derived radioactivity were also apparent in the liver and kidney at 30 min after intravenous administration. The localization within the liver demonstrated a mottled appearance, suggesting regions of higher uptake within the liver. In the kidney, the outer cortex consistently revealed the highest activity. PMID- 1514171 TI - The influence of infusions of 1-desamino-8-D-arginine vasopressin (DDAVP) in vivo on thrombin generation in vitro. AB - To investigate the effect of increasing FVIII:C in-vivo on coagulation ex-vivo, DDAVP was infused over 15 min in 10 volunteers and in-vitro thrombin generation measured. FVIII:C rose from 0.42 and 0.43 IU/ml before DDAVP to 1.38, 1.73 and 1.78 IU/ml at 15, 30 and 60 min respectively (p less than 0.001). A computer assisted thrombin generation test was performed in defibrinated plasma using chromogenic substrate, S2238. Time to reach 50% maximal thrombin activity (T50/s) and lag phase of thrombin generation (lag/s) were measured. Lag shortened from 75 and 60 s before to 45 s during and after infusion (p less than 0.001). T50 shortened from 78.5 and 76.0 to 62.5, 60.0 and 58.5 s at times 15 (p less than 0.01), 30 (p less than 0.001) and 60 (p less than 0.001) min. FVIII:C correlated inversely with lag and T50 (r = -0.847, p less than 0.001, r = -0.826, p less than 0.001, n = 10) respectively. These findings show that acute elevations of FVIII:C in-vivo accelerate in-vitro thrombin production. This work suggests that elevated FVIII:C levels in-vivo may be important in thrombo-occlusive disease. PMID- 1514172 TI - Screening for fibrin specific monoclonal antibodies: the development of a new procedure. AB - The acquisition of monoclonal antibodies specific for human fibrin has been impaired by the similarity in chemical composition between fibrinogen and fibrin and the conformational difference between immobilised and soluble fibrinogen. Five monoclonal antibodies (mabs) with a known affinity for fibrin have been subjected to screening procedures which involved the presentation of different forms of both fibrinogen and fibrin to the test mabs. It was observed by scanning electron microscopy that dried fibrin (denoted fibrin D), immobilised on the wells of PVC plates was morphologically similar to the fibrin found in human clots whereas PVC-immobilised fibrin monolayers (fibrin M) and a homogenised form of fibrin (fibrin FF) presented two very different morphological appearances. It was shown that lack of cross reactivity of a mab with an antigen (e.g. fibrinogen) was validly demonstrated only when both mab and antigen were present in the soluble state. These findings have allowed the generation of a screening procedure which involves the use of fibrin D on PVC plates in conjunction with whole human plasma incubated with the test antibody. This screening procedure has been validated using two mabs, one of which has an exclusive fibrin affinity while the other has a broad spectrum crossreactivity with both fibrinogen and fibrin. This procedure would ensure the acquisition of all the five fibrin specific mabs used in this study while other less reliable screening procedures might not. PMID- 1514173 TI - Reactivated recombinant plasminogen activator inhibitor-1 (rPAI-1) effectively prevents thrombolysis in vivo. AB - The effects of human recombinant plasminogen activator inhibitor (rPAI-1) on thrombolysis with recombinant tissue-type plasminogen activator (rt-PA) were studied in a rabbit model of jugular vein thrombosis. Two functionally distinct rPAI-1 preparations were used in these experiments, including latent rPAI-1 (approximately 2 units of t-PA neutralizing activity per micrograms protein) and reactivated rPAI-1 (approximately 150 units/micrograms). Simultaneous intravenous infusion over 4 h of 1.7 mg/kg of reactivated rPAI-1 (inhibitory capacity approximately 0.5 mg/kg rt-PA) with 0.5 mg/kg of rt-PA completely prevented lysis of a jugular venous thrombus, whereas an equivalent amount of latent PAI-1 did not significantly influence clot lysis. These findings demonstrate that reactivated human rPAI-1 efficiently neutralizes thrombolysis with rt-PA in vivo. Since previous studies have suggested that elevated endogenous levels of PAI-1 do not attenuate the thrombolytic potency of rt-PA in the endotoxin-treated model, we compared the stability of complexes formed by 125I-rt-PA with reactivated human rPAI-1 and with rabbit PAI-1 in vitro. Our findings indicate that both forms of PAI-1 form SDS-stable complexes following incubation with 125I-rt-PA. Thus, it seems likely that elevated levels of active PAI-1 can negate the thrombolytic effects of rt-PA in vivo and argues against the possibility that t PA can dissociate from PAI-1 and have its activity restored in the presence of a thrombus.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1514174 TI - The effect of thrombin inhibitors on tissue plasminogen activator induced thrombolysis in a rat model. AB - Successful coronary thrombolysis depends on rapidly restoring blood flow and maintaining patency of the infarct-related artery. Although widely used as an adjunct to lytic therapy, heparin is limited in its ability to produce these effects. Since the limitations of heparin may reflect its inability to inactivate clot-bound thrombin, we developed a rat model of tissue plasminogen activator (t PA) induced thrombolysis to compare doses of heparin, hirudin, hirulog (a synthetic hirudin-derived peptide), and D-Phe-Pro-ArgCH2Cl (PPACK) that produced a 4-fold prolongation of the baseline activated partial thromboplastin time (APTT) with saline in terms of their ability to accelerate thrombolysis and to prevent reocclusion. A thrombus rich in red cells and fibrin was formed in the distal aorta by applying an external constrictor after denuding the endothelium with a balloon catheter. Thrombolysis was induced with t-PA (1 mg/kg bolus, followed by 1 mg kg-1 h-1 over 30 min) and the rats were then randomized to receive a concomitant 80 min infusion of a thrombin inhibitor or saline. By continuously monitoring blood flow and pre- and post-stenotic blood pressures, the time to clot lysis, and the number of reocclusions were determined. Compared to saline, heparin had no significant effect on these variables.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1514175 TI - Inhibition of fibrinolytic activity in-vivo by dexamethasone is counterbalanced by an inhibition of platelet aggregation. AB - Dexamethasone decreases the fibrinolytic activity in cultured medium of several cell types by an induction of PAI-1 synthesis. As a result of this enhanced PAI-1 synthesis a prothrombotic state is expected in patients treated with dexamethasone. However, such a prothrombotic state is not reported as a major adverse effect. We have studied the effects of dexamethasone (dose range: 0.1-3.0 mg/kg) on the fibrinolytic system of rats after a 5 day pretreatment period. It appeared that dexamethasone dose dependently decreased the fibrinolytic activity (a dose of 1 mg/kg showed a reduction of about 40%). This reduced fibrinolytic activity could be functionally translated into an increased thrombus size as measured with a venous thrombosis model: thrombus size was increased by 50% with 1 mg/kg dexamethasone. No effects could be measured on the coagulation system, but it appeared that ex-vivo measured platelet aggregation was dose dependently inhibited by dexamethasone treatment. This effect resulted in-vivo in prolonged obstruction times as measured with a modified aorta-loop model. These results indicate that the expected prothrombotic state due to a diminished fibrinolytic activity caused by dexamethasone is counterbalanced by an inhibition of platelet aggregation. PMID- 1514176 TI - Thromboembolic disease--critical evaluation of laboratory investigation. AB - Previous studies of patients with thromboembolic disease have revealed an association either with hereditary anticoagulant protein deficiencies or with defects in the fibrinolytic system. To obtain a more comprehensive picture and to investigate which analyses are useful in the evaluation of such patients, we have performed an extensive laboratory investigation in 439 individuals with thromboembolic disease. Anticoagulant protein deficiencies were found in 24 patients. Deficiencies of protein C (n = 10) and protein S (n = 9) were most common followed by deficiencies of antithrombin III (n = 3) and plasminogen (n = 2). Six of the nine protein S deficient patients demonstrated a selective deficiency of free protein S with normal total protein S concentrations. To diagnose protein C and S deficiencies among the 201 patients receiving oral vitamin K antagonists, the concentrations of protein C and S were compared with the mean concentration of several other vitamin K-dependent proteins. One protein C and three protein S deficiencies were identified among the treated patients. The number of protein C deficiencies found in this group was significantly lower than the number found among untreated patients. Although fewer protein S deficiencies were also identified among the treated patients, than in the untreated group, the difference was not statistically significant. The results suggest that protein C deficiencies went undetected in the treated group and that oral anticoagulant therapy should be discontinued before efforts to diagnose protein C deficiency are made. We found no cases with heparin cofactor II deficiency. Lupus anticoagulant was present in 10 patients.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1514177 TI - Coagulation factor IXa binding to activated platelets and platelet-derived microparticles: a flow cytometric study. AB - Factor IX plays a central role in blood coagulation, since it can be activated by either XIa (intrinsic pathway) or tissue factor-VIIa (extrinsic pathway). Activated factor IX (IXa), in a surface-bound complex with factor VIIIa, then activates factor X. Platelets provide the catalytic surface upon which this Xase complex is assembled in vivo. We have used flow cytometry to examine binding of factor IXa to thrombin-activated platelets in the absence of added VIIIa. Platelet-bound IXa and platelet protein GPIb were detected by indirect immunofluorescence staining followed by two-color flow cytometric analysis. Microparticles were identified by their light scattering characteristics. Two binding sites for factor IXa were detected. The high affinity binding site saturated at about 10 nM, with a Kd of 1.6 nM. A second binding curve, with a Kd of about 100 nM, was observed at higher concentrations of IXa. The high affinity factor IXa binding sites comprise about 7% of the total factor IXa binding. Binding to both sites was dependent on the presence of calcium. Thus, we conclude that factor IXa, in addition to its high affinity binding, has a calcium dependent low affinity association with activated platelets and microparticles. Sims et al, have shown that binding sites for a different coagulation factor, factor Va, are concentrated on microparticles relative to platelet membrane proteins, such as GPIb. GPIb is distributed on platelets and microparticle in proportion to plasma membrane surface.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1514178 TI - ADP receptor induced activation of guanine nucleotide binding proteins in rat platelet membranes--an effect selectively blocked by the thienopyridine clopidogrel. AB - The thienopyridine clopidogrel, a potent analog of ticlopidine, is a powerful inhibitor of ADP induced platelet aggregation and ADP induced inhibition of cyclic AMP accumulation in intact platelets but not of ADP induced shape change. We have recently demonstrated that ADP stimulates the binding of GTP gamma S to GTP binding proteins (G proteins) in human platelet membranes. We now studied the effects of clopidogrel, a specific inhibitor of ADP induced platelet aggregation on the stimulation of GTP gamma S binding to rat platelet membranes by ADP. Using the non hydrolyzable stable analog of ADP, 2MeSADP, we demonstrate that 2MeSADP stimulates the binding of [35S]GTP gamma S to rat platelet membranes in a concentration dependent manner, that this effect is inhibited by the specific ADP receptor antagonist Sp-ATP alpha S and that clopidogrel completely and selectively blocks the stimulation by 2MeSADP of [35S]GTP gamma S binding to platelet membranes of treated rats. We conclude that: i) rat platelet membranes possess an ADP receptor coupled to unidentified G protein(s) and ii) the thienopyridine clopidogrel impairs the interaction of the ADP receptor with its G protein by an irreversible modification the ADP receptor itself or its putative G protein. PMID- 1514179 TI - Recommended protocol for the study of the ex vivo biological effects of virus inactivated plasma concentrates in patients with von Willebrand disease. The von Willebrand Factor Subcommittee of the Scientific and Standardization Committee of the International Society on Thrombosis and Hemostasis and of the von Willebrand Disease Committee of the World Federation of Hemophilia. PMID- 1514180 TI - The effect of residual heparin on the interpretation of heparin-induced platelet aggregation in the diagnosis of heparin-associated thrombocytopenia. PMID- 1514181 TI - Noninvasive diagnosis of deep venous thrombosis: lesson from the debate about computerized impedance plethysmography. PMID- 1514182 TI - Thrombin generation in thrombotic thrombocytopenic purpura. PMID- 1514183 TI - Contact activation, heparins and cardiopulmonary bypass. PMID- 1514184 TI - Platelet factor 4 complexed to heparin is the target for antibodies generated in heparin-induced thrombocytopenia. PMID- 1514185 TI - Modulation of aflatoxin B1 biotransformation in rabbit pulmonary and hepatic microsomes. AB - Aflatoxin B1 (AFB1) is a carcinogenic mycotoxin that requires activation to the corresponding 8,9-epoxide for activity. In addition to being present in foodstuffs, AFB1 can contaminate respirable grain dusts and thus the respiratory system is a potential target for carcinogenesis. In the present study, we have investigated the role of polycyclic aromatic hydrocarbon-inducible forms of cytochrome P-450 in the pulmonary and hepatic microsomal activation ([3H]AFB1-DNA binding) and detoxification ([3H]AFM1 and [3H]AFQ1 formation) of [3H]AFB1. In rabbit lung microsomes, the apparent Vmax for [3H]AFM1 formation was increased significantly when values were expressed per mg microsomal protein or per nmol P 450 present. In liver microsomes, the apparent Vmax for DNA binding and [3H]AFM1 formation were increased by beta-naphthoflavone (BNF) treatment (to 2.3 and 3.3 times control, respectively) when expressed per mg protein, but when expressed per nmol P-450, only AFM1 formation was significantly increased. The apparent Km values for both these reactions were unaffected. The apparent Vmax for [3H]AFQ1 formation was not affected by BNF treatment, but the apparent Km was increased to 4.5 times control. Boiling of microsomes or omitting the NADPH-generating system decreased DNA binding, AFM1 formation and AFQ1 formation by 89-97%, while addition of 1.0 mM SKF-525A inhibited these reactions by 46-57%. Addition of 1.0 mM alpha-naphthoflavone (ANF) had no effect on the biotransformation of [3H]AFB1 in lung microsomes of control rabbits, but significantly decreased AFM1 formation (by 31%) in lung microsomes from BNF-treated animals (other reactions were unaffected). In liver microsomes from BNF treated rabbits, 1.0 mM ANF inhibited DNA binding of [3H]AFB1 by 68%, while there was no effect in control microsomes. ANF significantly inhibited AFM1 formation in liver microsomes from both control and BNF-treated animals (by 87-97% and 67-78% at 1.0 mM and 2.0 microM, respectively), but had no effect on AFQ1 formation in liver microsomes from animals in either treatment group. These results indicate an important role for the 1A subclass of P-450 isozymes in the biotransformation of AFB1 to AFM1 in rabbit lung and liver, and a minor role in AFB1 activation in liver. PMID- 1514187 TI - High carbonyl reductase activity in adrenal gland and ovary emphasizes its role in carbonyl compound detoxication. AB - Carbonyl reduction has been studied in liver, kidney, adrenal gland and ovary of female Wistar and Sprague-Dawley rats as well as of female NMRI mice by using metyrapone as a substrate and by means of direct HPLC analysis of the reduced alcohol metabolite metyrapol. Carbonyl reducing activities were found in all tissues examined so far, with that in rat ovary and adrenal gland cytosol exceeding the liver cytosolic specific activity severalfold: 15-fold and 12-fold in the Wistar strain; 12-fold and 7-fold in the Sprague-Dawley strain, respectively. In general, Wistar rat enzyme activities were about four times higher than those of Sprague-Dawley rats in all fractions, which indicates an interesting genetic difference between the two rat strains. Due to the sensitivity towards the diagnostic inhibitor quercitrin, carbonyl reductase (EC 1.1.1.184) seems to be mainly responsible for metyrapone reduction in rat and mouse adrenal gland and ovary cytosol. However, sensitivity towards dicoumarol in microsomal fractions of mouse tissues points to the involvement of further carbonyl reducing enzymes. Western blot experiments revealed immunological differences between metyrapone reductase from liver microsomes and respective enzymes of all other tissues. In conclusion, the difference in tissue and intracellular distribution suggests that several enzymes are involved in carbonyl reduction of metyrapone and the intracellular multiplicity of the enzymes may have some relation to their significance in carbonyl compound detoxification. These results support the hypothesis that carbonyl reductases, besides their participation in the metabolism of physiologically occurring substances, provide the enzymatic basis for the detoxification of xenobiotic carbonyl compounds in adrenal gland and ovary which have escaped their metabolic conversion by the liver. PMID- 1514186 TI - Antioxidant-dependent inhibition of diquat-induced toxicity in vivo. AB - The abilities of two experimental antioxidants (U-74006F and U-78517G), as well as the model antioxidant, diphenyl-p-phenylenediamine (DPPD), to protect against diquat-induced toxicity in male Fischer-344 rats were examined. Both experimental compounds afforded near complete protection against diquat-induced hepatotoxicity, as measured by clinical chemistry and histopathological indices. When observed, diquat-induced nephrotoxicity was also inhibited. Minimal protection was afforded by the model compound, DPPD. In follow-up studies with U 78517G, no effect on diquat-induced biliary excretion of oxidized glutathione was observed, suggesting that a shift in the thiol:disulfide ratio is not responsible for diquat-induced hepatotoxicity. These data are consistent with those from previous in vitro studies in our laboratory and are in agreement with studies by others which suggest that lipid peroxidation is an important event in diquat induced hepatotoxicity in vivo. The antioxidant effects were largely route independent as either oral pre-treatment alone (200 mg/kg, 24 h before diquat), intravenous pre-treatment alone (6 mg/kg, 5 min before diquat) or the combination of both treatments produced a similar degree of protection. While pre-treatment with antioxidants was quite effective, no significant U-78517G-dependent inhibition of toxicity was observed when administration was delayed by as little as 10 min post diquat. These latter data suggest that initiation of diquat induced hepatotoxicity is rapid and that these compounds would therefore be unlikely to have clinical utility in the treatment of diquat intoxication. PMID- 1514188 TI - Differences between rats and mice in the immunosuppressive activity of 2 methoxyethanol and 2-methoxyacetic acid. AB - Previous studies from this laboratory have demonstrated that 2-methoxyethanol (ME) and its principal metabolite 2-methoxyacetic acid (MAA) are immunosuppressive in young adult male Fischer 344 rats. In the present study, the immunosuppressive potential of ME and MAA was evaluated in young adult female Fischer 344 rats and C57BL/6J mice. Rats and mice were dosed by gavage with either ME or MAA in water, at dosages ranging from 50-400 mg/kg/day, for 10 consecutive days. Rats and mice were examined for alterations in body, spleen and thymus weights and mitogen-induced proliferation of splenic lymphocytes in vitro; separate groups were employed for the antibody plaque-forming cell (PFC) response to trinitrophenyl-lipopolysaccharide (TNP-LPS). Rats dosed at 100-400 mg/kg/day ME and rats dosed at 50-400 mg/kg/day MAA had decreased thymus weights in the absence of decreased body or spleen weights. Lymphoproliferative (LP) responses to concanavalin A (Con A), phytohemagglutinin (PHA), pokeweed mitogen (PWM) and Salmonella typhimurium mitogen (STM) were all reduced in rats treated with all dosages of ME. Rats treated with MAA displayed similar reductions in these LP responses except that the responses to PWM and STM in rats dosed at 50 mg/kg/day were not reduced. In contrast to the effects of ME and MAA on these end points in the rat, no thymic involution or suppression of LP responses were observed in mice dosed at 50-400 mg/kg/day. The PFC response to TNP-LPS was suppressed in rats dosed with either ME or MAA at dosages of 100-400 mg/kg/day. ME and MAA, however, failed to suppress the PFC response in mice immunized with TNP-LPS. These results indicate that unlike Fischer 344 rats, C57BL/6J mice are insensitive to the immunosuppressive effects of ME and MAA at the dosages employed in this study. Whether the different sensitivities of these two rodent species to ME- and MAA-induced immunosuppression are due to immunologic, pharmacokinetic or metabolic differences within each species remains to be determined. PMID- 1514189 TI - D-penicillamine and prussian blue as antidotes against thallium intoxication in rats. AB - D-penicillamine (DP) and prussian blue (PB), given alone and in combination, were evaluated in rats as treatments against acute thallotoxicosis. Animals were poisoned by intraperitoneal (i.p.) injection of thallium(I) acetate at different doses (16, 30, 40, 50 and 70 mg/kg). Later (24 h), treatments were administered until day 5, as follows: D-penicillamine (DP), 25 mg/kg, i.p. route, twice daily; prussian blue (PB), 50 mg/kg, oral route, twice daily. LD50 values were estimated for each treatment with the following results: control, 32 mg/kg; DP, 27 mg/kg; PB, 42 mg/kg; PB + DP, 64 mg/kg. Thallium content was analyzed in six body organs and eight brain regions after treatments. PB administration induced significant elimination of thallium from all tissues. DP treatment diminished thallium content in body organs, but increased it in brain regions, indicating a redistributive effect of DP. DP + PB treatment decreased thallium content in all body organs and brain regions. Renal thallium content in the DP + PB group was significantly lower than that of PB alone group, suggesting accelerated urinary excretion of thallium as a result of DP action. Results indicate that DP administered alone may be dangerous because of its redistributive effect, but given in combination with PB may be useful as treatment against thallium poisoning. PMID- 1514190 TI - Role of para-hydroxylation in phensuximide-induced urotoxicity in the Fischer 344 rat. AB - Phensuximide (PSX) is an antiepileptic agent which has been shown to induce hemorrhagic cystitis and mild nephrotoxicity following repeated administration in man or rats or when acutely administered to phenobarbital-pretreated rats. The purpose of this study was to explore the role of para-hydroxylation of the phenyl group of PSX in PSX-induced urotoxicity. Two PSX derivatives, 2-(4-fluorophenyl) N-methylsuccinimide (FMPS) and N-methyl-2-(4-methylphenyl)succinimide (MMPS), were synthesized and evaluated for urotoxic potential. Male Fischer 344 rats (four rats/group) were administered intraperitoneally (i.p.) a succinimide (0.4 or 1.0 mmol/kg) or vehicle and renal function monitored for 48 h. In a separate experiment, rats were pretreated with phenobarbital (75 mg/kg/day; 3 days, i.p.) prior to succinimide or succinimide vehicle. In non-phenobarbital pretreated rats, acute FMPS or MMPS treatment had little effect on renal function or morphology at the doses tested. Hematuria (+) was noted in the FMPS (1.0 mmol/kg) group on post-treatment day 2. However, in the phenobarbital-pretreated rats, FMPS (0.4 or 1.0 mmol/kg) induced marked hematuria (++) and increased proteinuria while having little or no effect on other renal functional parameters or renal morphology. At killing, bladders of treated rats were distended with bloody urine and exhibited hemorrhagic areas within the bladder wall. In phenobarbital pretreated rats, MMPS administration had little effect on any renal functional parameter measured or urological morphology. These results suggest that para hydroxylation does not contribute to the hemorrhagic cystitis induced by PSX. PMID- 1514191 TI - Cadmium exposure inhibits the prolactin secretory response to thyrotrophin releasing hormone (TRH) in vitro. AB - In vitro dose response (0.1-100 microM) and time course studies were performed on anterior pituitary cells isolated from female Sprague-Dawley rats in the diestrous stage of the estrous cycle. All doses of TRH produced a significant increase in prolactin release by 5 min which was sustained for 30 min. Pretreatment with 25 or 50 microM Cd for 2 or 4 h produced a significant decrease in prolactin secretion during Cd exposure and in the prolactin secretory response to 1 microM TRH. These results suggest that Cd pretreatment alters the subsequent ability of the lactotrophs to respond to the physiological secretagogue TRH. This alteration does not appear to be due to a rebound phenomenon since basal prolactin release was the same in Cd-pretreated and control cells once the metal was removed. These results suggest that Cd pretreatment produces a significant decrease in prolactin release from the anterior pituitary lactotrophs in response to subsequent TRH stimulation in vitro. PMID- 1514192 TI - High pressure effects on reflexes in isolated spinal cords of newborn rats. AB - High pressure induces hyperexcitability and convulsions in both intact and decerebrated animals. However, pressure suppresses synaptic transmission in isolated invertebrate preparations. We examined the effect of high pressure on monosynaptic (MSR) and polysynaptic (PSR) reflexes in isolated spinal cords of newborn rats. Reflex activity was recorded extracellularly from the cut ends of the lumbar ventral roots L3-L5 following stimulation of the corresponding dorsal roots. Increasing the stimulus frequency from 0.1 to 2.0 Hz reduced the amplitude of both reflexes by 75%. High pressure (10.1 MPa helium) did not affect this phenomenon. Pressure had no effect on MSR amplitude, but increased PSR amplitude by 30%. For MSR, pressure increased the latency by 25%, duration by 20%, and rise time by 25%. Pressure abolished the moderate (119 +/- 4.5%, mean +/- SEM) posttetanic potentiation observed at 0.1 MPa. For the curve relating MSR amplitude to [Ca2+]o, high pressure produced a slight rightward shift of 0.25 mM without affecting its saturation level. These data suggest that the response of vertebrate central synapses to pressure may be different from previously described invertebrate synapses. Alternatively, if synaptic potentials are reduced at high pressure, other processes that determine excitability must be invoked to account for the relatively stabile reflex response. PMID- 1514194 TI - [Oncology in transition]. PMID- 1514193 TI - Paradoxical air embolism in pigs with a patent foramen ovale. AB - Recent studies have indicated that divers with a patent foramen ovale (PFO) are at risk of developing some forms of decompression sickness. Thus, the objective of the present study was to investigate if the occurrence of paradoxical air embolism (PAE) was enhanced in pigs with a PFO compared to the occurrence in pigs without such a defect. Out of 54 pigs, 18 had a PFO (group PFO), and the other 36 composed the controls (group C). The pigs were anesthetized, mechanically ventilated, and received venous air infusion at four different rates (0.050, 0.075, 0.100, and 0.200 ml.kg-1.min-1). PAE was monitored by use of a transesophageal echocardiographic probe to detect if any arterial air bubbles were present in the left atrium or the aorta. We found that PAE appeared at a lower infusion rate in group PFO than in group C. When PAE occurred, the mean pulmonary arterial pressure and the mean arterial pressure were significantly higher in pigs with a PFO than in the control pigs. Finally, the infused air volume per kilogram of body weight in group PFO was significantly lower than that observed in group C. The results demonstrated that the risk of PAE occurring in mechanically ventilated pigs with a PFO was greater compared to the risk observed in pigs without a PFO. PMID- 1514195 TI - [Value of imaging procedures in staging prostate cancer. Is CT out?]. PMID- 1514196 TI - [Risk-oriented classification of superficial bladder cancers]. PMID- 1514197 TI - [Indications for topical therapy in superficial bladder cancer]. PMID- 1514198 TI - [What is the value of urine cytology in after-care of patients with urothelial cancers?]. PMID- 1514199 TI - [Improved classification of metastatic testicular cancer]. PMID- 1514200 TI - [Current status of lymph node excision in penile cancer]. PMID- 1514201 TI - [Modified lymphadenectomy in testicular tumor]. PMID- 1514202 TI - [Adjuvant and inductive chemotherapy of testicular tumor]. PMID- 1514203 TI - [Adjuvant and neoadjuvant therapy in bladder and prostatic cancer]. PMID- 1514204 TI - [Are immunotherapy and chemotherapy in metastatic renal cell cancer out?]. PMID- 1514206 TI - [Research acceptance in transition]. PMID- 1514205 TI - [The development of urinary diversion]. PMID- 1514207 TI - [Hypospadias--current surgical procedures]. AB - The treatment of hypospadias has developed over the years from a disabling intervention to a surgical procedure devised with due consideration for the needs of paediatric patient. The operation is timed to fit in with the child's psychological development, being performed early in life before it becomes too traumatic for the child. Resection of the chordee and creation of the neourethra in a single session is increasingly superseding the two-stage procedure usual earlier, especially for distal and medial hypospadias. However, when the surgeon is sufficiently experienced even proximal hypospadias can be corrected in a single session, for example by a combination of a Thiersch and a free island flap or by free bladder mucosal flaps or grafts. The use of suitably fine instruments and suture material should be a matter of course, as should the use of magnifying lenses. Urinary diversion is still obligatory in most centres, and, like the sort of dressing used, it depends on the individual experience and judgement of the surgeon. The incidence of postoperative complications should be below 10% regardless of the degree of hypospadias. PMID- 1514208 TI - [Chromosome abnormalities in hypospadias? An analysis of 131 patients]. AB - We performed chromosome studies in 131 patients presenting with hypospadias, with the aim of detecting any causal connections between chromosomal abnormalities and the induction of hypospadias. Autosomal abnormalities were revealed in 6 and sex chromosomal abnormalities in 10 patients. Although a significant causal relationship between the occurrence of hypospadias and chromosomal abnormalities was seen in this study in only two cases of mixed gonadal dysgenesis (45,X/46,XY and streak gonad), the high incidence of chromosomal abnormalities observed (12.2%) seems noteworthy compared with the incidence of only 0.61% in the normal male population. PMID- 1514209 TI - [Prognostic parameters of scar progression, new scar formation and maturation in primary vesico-ureteral-renal reflux]. AB - We analysed the data recorded for 901 children (1357 kidneys) treated for primary vesicoureteral reflux between 1973 and 1988 at our institution. The retrospective study showed a rate of 7.3% for new renal scarring and progression; analysis by reflux grade revealed progression and new scarring in reflux, 10.9% of cases with grade IV and 16.5% of cases with grade V whereas low grades (I and II) were followed by no scarring at all. A close correlation of new scarring with urinary tract infection and bladder function was demonstrated. Spontaneous resolution of reflux was observed in 33.6% of all patients and in only 2.6% of patients with grade V reflux, as against a 85.5% resolution rate in patients with grade I or II reflux. A different sex distribution was revealed in the age group under 1 year, in which 80% of the patients were boys and the resolution rate was higher than in any other age group. PMID- 1514210 TI - [Reflux nephropathy: decreased renal function and osteodystrophy]. AB - In the early stages of chronic renal failure in childhood renal osteodystrophy is a therapeutic challenge, since in childhood it is mainly growth that is affected. The clinical appearance, pathophysiology and therapy are discussed with reference to an actual case of reflux nephropathy in a child. PMID- 1514211 TI - [ESWL in hemophilia B]. AB - One of the most dramatic dangers in treating nephrolithiasis by ESWL is the development of intra- and perirenal bleeding, which requires therapeutic intervention. Even in patients whose blood parameters suggest they are healthy, hematomas are found in up to 80%. Therefore, ESWL must be regarded as contraindicated in patients with blood disorders. A case of a patient suffering from hemophilia B and from a large renal pelvic stone is reported, whom we treated by ESWL twice after sufficient substitution. X-ray revealed that the patient was stone-free on the 25th day after the first ESWL session. ESWL. A review of the literature is presented. PMID- 1514212 TI - [Is down-staging of advanced bladder cancer by neoadjuvant chemotherapy possible? -MVEC protocol]. AB - In 22 patients with advanced transitional cell carcinoma of the bladder, neoadjuvant chemotherapy according to the MVEC regimen was given. Subsequent radical cystectomy showed down-staging in 7 patients (32%). The preoperative clinical staging revealed regression of the bladder cancer in 77% of all cases. Down-grading was seen in only 2 patients. Because of the discrepancy between preoperative clinical staging and the histopathological staging after radical cystectomy, invasive tumour surgery is necessary even when clinical staging has not revealed a tumour after chemotherapy. PMID- 1514213 TI - [Polychemotherapy in advanced bladder cancer. Practicality and clinical results]. AB - From 1987 to 1990 a consecutive series of 172 patients were treated for advanced bladder cancer, in our clinic, 48 of whom underwent radical cystectomy. In 80 of the remaining 124 patients polychemotherapy was not possible, because of impaired renal function, poor performance status, cardiovascular disease, second malignancy or other problems. There were 11 patients who refused further treatment and 13 patients with tumor restricted to the pelvis who underwent radiochemotherapy. Thus, 20 patients received polychemotherapy with either methotrexate, vinblastine, Adriamycin and cisplatin (M-VAC) or cisplatin, methotrexate and vinblastine (CMV). In 90% of the M-VAC cycles and 34% of the CMV cycles dose reduction was necessary. Median survival was 10 months. We achieved 2 complete responses lasting 6 months and 19 months and 4 partial responses. The authors conclude that patients who cannot undergo radical surgery for bladder cancer are not good candidates for polychemotherapy either. Only patients with measurable remission of the tumour have a longer survival. New regimens with lower toxicity, and especially with lower renal toxicity, must be developed. PMID- 1514214 TI - Microscopic and ultrastructural studies of necrotizing hepatopancreatitis in Pacific white shrimp (Penaeus vannamei) cultured in Texas. AB - Granulomatous hepatopancreatitis of unknown etiology has been considered an important disease of Texas shrimp mariculture since 1985. Samples of Pacific white shrimp (Penaeus vannamei) were collected during 1986, 1987, and 1990 from three farms and an experimental mariculture facility with histories of production loss and increased mortality rates. Histologic and ultrastructural examination of shrimp from the four sites demonstrated two morphologically distinct, Gram negative, double-enveloped, intracytoplasmic bacteria in necrotic hepatopancreatic epithelium. The more numerous small, pleomorphic rod as well as the helical organism are both taxonomically unclassifiable. The helical organism lacked ultrastructural characteristics of previously described helical or spiral bacteria. The relationship between the two organisms is unknown, but the pleomorphic rod is thought to play a major role in the disease. The role of a bacterial agent(s) in subsequent disease episodes is suggested by the observation that the use of oxytetracycline-medicated feed resulted in increased production and survival. Hepatopancreatic tubular epithelial necrosis and shrimp mortality correlated directly with the extent of infection by the small pleomorphic rod. Individual discrete bacteria were identified microscopically by Steiner and Steiner's method. Three major developmental stages of the disease were characterized based on the extent and number of hepatopancreatic tubular epithelial cells containing bacteria, the degree of tubular interstitial inflammation, and the extent and chronicity of tubular necrosis. Additional studies are needed to clarify the roles of the different bacteria identified and the potential role of environmental factors on the disease process. PMID- 1514215 TI - Age-related changes in thyroid structure and function in Sprague-Dawley rats. AB - Investigation of thyroid glands from 500 male and 500 female Sprague-Dawley rats, at time points of 8, 17, 30, 56, and 108 weeks of toxicity studies conducted at the Huntingdon Research Centre between 1981 and 1984, revealed age-related structural and functional changes that have previously not been well documented. The number of ultimobranchial cysts decreased with age, while area(s) of C-cell hyperplasia appeared with age. Beginning at 56 weeks, some of the thyroid follicles were hyperdistended with colloid, had irregular lumens, and were lined by flattened epithelium. These follicles had clumped, granular, and stratified colloid. Follicular tumors were found in 8% of the males and 6% of the females at 108 weeks. There was an increase in absolute thyroid weights (males from 21.8 +/- 4.0 g to 46.5 +/- 19.05 g, females from 17.2 +/- 4.53 g to 41.7 +/- 26.92 g) and body weights (males from 382.0 +/- 70.6 g to 806.0 +/- 120.7 g, females from 220.0 +/- 21.0 g to 495.0 +/- 127.3 g) with age in both sexes, but the relative thyroid weights were not significantly affected. Negative allometry was observed. With an increase in the age of the rats, there was a decrease in the height of the follicular epithelium and an increase in the internal follicular diameter and the total number of follicles. No prediction for sex could be detected. Serum T3 and T4 concentrations were constant until 56 weeks of age, but at 108 weeks, the values were markedly reduced (in males, serum T3 concentration decreased from 91.60 +/- 13.970 ng/100 ml to 32.90 +/- 10.878 ng/100 ml, and in females, from 90.80 +/- 11.338 ng/100 ml to 48.10 +/- 8.875 ng/100 ml; in males, serum T4 concentration decreased from 5.94 +/- 0.679 microgram/100 ml to 3.04 +/- 0.604 microgram/100 ml, and in females, from 4.59 +/- 0.717 microgram/100 ml to 2.77 +/ 0.786 microgram/100 ml). The data suggest that the thyroid function of Sprague Dawley rats reduces as the rats age. PMID- 1514216 TI - Brain lesions of naturally occurring pregnancy toxemia of sheep. AB - The neuropathology and biochemical features of 17 sheep with clinical signs and gross necropsy features of naturally occurring pregnancy toxemia were retrospectively evaluated. The sheep ranged in age from 3 to 6 years and were of seven different breeds and three breed crosses. Thirteen sheep (case Nos. 1-4, 6 9, 11-14, 16) showed astrocytic nuclear swelling, hypertrophy and proliferation, and cerebrocortical neuronal necrosis. Seven of these sheep had Purkinje cell necrosis (case Nos. 2, 3, 6, 11, 12, 14, 16), and seven had vacuolation of cerebral and cerebellar sub-cortical white matter (case Nos. 1-4, 9, 12, 13). The neuropathologic features were similar to those of naturally occurring hypoglycemia of human beings and experimentally induced hypoglycemia of primates and the rat. The lesions seen in the sheep studied may have been caused by cerebral hypoglycemia, but data for blood or cerebral glucose concentrations were not available. PMID- 1514217 TI - Carbonic anhydrase localization in normal and osteochondrotic joint cartilage of growing pigs. AB - The histochemical localization of carbonic anhydrase in the normal and osteochondrotic epiphyseal growth cartilage from 15 growing pigs (6 to 18 weeks old) was studied. All animals were clinically normal. The entire thickness of the articular-epiphyseal cartilage complex from the femoral condyles was fixed in 2% glutaraldehyde and embedded in a water-soluble glycolmethacrylate. Sections (1-2 microns) were incubated on the surface of a medium containing cobalt, phosphate, and bicarbonate. A black precipitate formed at sites of enzymatic activity. This method shows the activity of all different isoenzymes of carbonic anhydrase. The specificity was checked by adding the carbonic anhydrase inhibitor acetazolamide to the incubation medium. Osteochondrosis in the epiphyseal growth cartilage was characterized by chondronecrotic areas in resting, proliferative, hypertrophic, and calcifying regions. When the hypertrophic and calcifying regions were involved, insufficient cartilage calcification and focally impaired ossification were seen. The chondronecrotic areas were surrounded by groups of morphologically viable cells, or so-called "clusters." Carbonic anhydrase was present in chondrocytes of hypertrophic and calcifying regions of the normal growth cartilage and in osteoclasts and erythrocytes. No evidence of carbonic anhydrase activity was found in the articular cartilage or in the resting region of normal growth cartilage in any of the pigs. No enzyme activity was found in the osteochondrotic cartilage, either in clusters or dead cells. The lack of carbonic anhydrase in the osteochondrotic cartilage demonstrated in this study may result in an inability to produce the alkaline matrix necessary for calcification and could be one reason for the insufficient calcification typical of this cartilage. PMID- 1514218 TI - A retrospective clinicopathologic study of 212 dogs with cutaneous hemangiomas and hemangiosarcomas. AB - The relationship between skin pigmentation and piliation and the development of hemangiomas and hemangiosarcomas in the dermis and subcutaneous tissue was studied in 212 dogs. These 212 dogs had a combined total of 306 tumors; 38 of these 212 dogs had two or more of the same tumor in a different location or a combination of hemangioma and hemangiosarcoma. The average age of the dogs at the time of excision of these tumors was greater than 10 years. There was no sex predilection for the presence or absence of tumors. Cutaneous hemangiomas (73%) were more common than cutaneous hemangiosarcomas (27%). Hemangiomas had no predilection for dermis (51%) or subcutaneous tissue (47%), but hemangiosarcomas had a marked predilection for dermis (73%) over subcutaneous tissue (7%). Dogs with short hair coats and lightly pigmented skin had more hemangiomas and hemangiosarcomas of the dermis (65%) than did dogs with variable length hair coats and pigmentation (28%). Dogs with short hair coats and lightly pigmented skin had fewer hemangiomas and hemangiosarcomas of the subcutaneous tissue (10%) than did dogs with variable length hair coats and pigmentation (22%). Dogs with short hair coats and lightly pigmented skin also had more hemangiomas and hemangiosarcomas of ventral glabrous skin (65%) than did dogs with variable length hair coats and pigmentation (22%). In addition, there was no predilection of subcutaneous hemangiosarcoma for haired (33%) versus glabrous (33%) skin, but dermal hemangiosarcoma had a marked predilection for the glabrous skin (63%) when compared with haired skin (10%). The increased incidence of dermal hemangiomas and hemangiosarcomas in ventral glabrous skin suggests an association between solar radiation and the biologic properties of glabrous skin in the genesis of these tumors. PMID- 1514219 TI - Cutaneous vascular neoplasia in 15 cats: clinical, morphologic, and immunohistochemical studies. AB - Seven cases of cutaneous hemangioma and nine of cutaneous hemangiosarcoma were diagnosed from biopsy specimens of 15 Domestic Shorthairs of 5,091 cats that were examined by necropsy or biopsy during the 5-year period from 1 January 1986 through 31 December 1990. All but three cats were male. Tumor cells of both hemangiomas and hemangiosarcomas were immunoreactive for factor VIII-related antigen and for vimentin by the avidin biotin peroxidase complex method. In cats with a median age of 10 years, hemangiomas occurred in skin with pigmented hair in six of seven cases without apparent site predilection. These solitary tumors did not recur after excision although one cat (No. 3) subsequently developed cutaneous hemangiosarcoma at another site. Seven of nine hemangiosarcomas occurred in dermis and subcutis of the head, usually on the pinna. All five hemangiosarcomas of the head, for which cutaneous pigmentation could be determined, occurred in unpigmented skin. Cats with hemangiosarcoma had a median age of 12.5 years at the time of diagnosis. Metastasis has not been documented, but hemangiosarcoma has recurred, from 1 month to 2 years after excision, in 6/7 cats that were studied. PMID- 1514220 TI - A pathologic and bacteriologic study on otitis media in swine. AB - A pathologic and bacteriologic study on otitis media in swine was performed on 237 swine, ranging in age from 1 day to 1 year. These 237 swine from eight selected farms were slaughtered due to unfavorable prognosis associated with clinical signs of illness. One hundred sixty-three (68.8%) of the 237 swine were found to be affected with otitis, though only a few swine showed clinical signs characteristic of the disease. One hundred fifty-one (63.7%), 53 (22.4%), and 39 (16.5%) had lesions in the middle, external, and internal ear, respectively. Of the 151 cases with otitis media, bilateral and unilateral infection accounted for 114 (75.5%) and 37 (24.5%), respectively. Only 5/53 swine with otitis externa and 6/39 swine with otitis interna failed to show otitis media. All swine with infection in the tympanic cavity had inflammatory lesions in the auditory tube. Examination of the swine grouped by age revealed that, regardless of age, incidence of otitis media was 50-70%. In swine younger than 1 month old, otitis media tended to center on the auditory tube, where a mild infiltration of neutrophils into the mucous membrane was frequent. Thereafter, otitis media increased in degree and extent with age. Forty (26.5%) of the 151 swine affected with otitis media were accompanied by a substantial amount of inflammatory exudate in the tympanic cavity and bulla. Purulent exudate was found in 20/40 (50%) swine. Severe otitis media prevailed in swine between 1 and 4 months of age, showing inspissation of a suppurative exudate in the tympanic cavity and lysis of the underlying osseous wall of the tympanic bulla with subsequent fibrosis.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1514221 TI - Effects of humoral hypercalcemia of malignancy on the parathyroid gland in nude mice. AB - The ultrastructure of parathyroid chief cells was examined from four groups of nude mice (NIH:Swiss) with different serum calcium concentrations. The groups consisted of eight male mice with hypercalcemia induced by transplantable canine adenocarcinoma (CAC-8), eight female mice with hypercalcemia induced by infusion of parathyroid hormone-related protein, ten male control mice, and six male mice fed a low calcium (0.01%) diet. Hypercalcemia induced by malignancy or parathyroid hormone-related protein infusion was associated with low serum phosphorus concentration, a decrease in the number of secretory and prosecretory granules in the parathyroid chief cells, and an increase in the cytoplasmic area of chief cells. Prominent myelinlike membranous whorls were present in the cytoplasm of chief cells of tumor-bearing and parathyroid hormone-related protein infused hypercalcemic mice. Mice fed a low calcium diet had decreases in the number of secretory granules and cell area but increases in the number of prosecretory granules compared with control mice. The number of mitochondria and the nuclear area of chief cells were similar in all four groups. The prominent membranous whorls and increased cytoplasmic area of chief cells from these hypercalcemic mice mark these cells as distinctly different from the parathyroid chief cells of other species with hypercalcemia. PMID- 1514222 TI - Malignant melanomas in a penguin (Eudyptes chrysolophus) and a red-tailed hawk (Buteo jamaicensis). PMID- 1514223 TI - Neurohypophyseal astrocytoma (Pituicytoma) in a rhesus monkey (Macaca mulatta). PMID- 1514224 TI - Eastern equine encephalomyelitis in an adult cow. PMID- 1514225 TI - Cutaneous mastocytosis in a dog. PMID- 1514226 TI - Stillbirth/perinatal weak calf syndrome: preliminary pathological, microbiological and biochemical findings. AB - Microbiological, biochemical and pathological data collected from 293 calves which were either stillborn, or born alive and either failed to breathe or failed to breathe for more than about 10 minutes are presented. No bacteria were recovered from 96 of the calves (32.7 per cent), and bacteria which were considered significant were isolated from only four (1.4 per cent). Evidence of leptospiral infection was found in 75 calves (25.5 per cent). Of 64 calves examined for bovine virus diarrhoea (BVD) and infectious bovine rhinotracheitis (IBR) antigens, two were positive for BVD virus and none for IBR virus. The mean (+/- sd) liver vitamin E and kidney selenium concentrations, determined in 148 of the calves, were 2.0 +/- 0.76 micrograms/g wet matter and 0.47 +/- 0.17 micrograms/g wet matter, respectively. The thyroid iodine concentration in 15 of 71 calves (21 per cent) was less than 300 micrograms/g wet matter and the mean (+/- sd) thyroid weight of 266 of the calves was 18.5 +/- 11.6 g. Evidence of severe trauma was found in 19 of the calves (6.5 per cent). Histological findings included thyroid epithelial hyperplasia, hepatic haemosiderosis, erythrophagocytosis in the spleen, perivascular haemorrhage in brain and adrenal glands, and accumulation of leucocytes in blood vessels. PMID- 1514227 TI - Efficacy of moxidectin, nemadectin and ivermectin against an ivermectin-resistant strain of Haemonchus contortus in sheep. AB - The efficacies of ivermectin, nemadectin and moxidectin were evaluated when administered orally to lambs infected with either a susceptible laboratory strain of Haemonchus contortus or a strain reported to be resistant to ivermectin. Groups of 24 Dorset cross Cheviot cross Suffolk lambs were infected with either the susceptible or resistant strain of H contortus and allocated to treatment groups according to their faecal egg counts 27 days after infection. One day later the lambs were dosed orally with one of the three anthelmintics at 0.2 mg/kg bodyweight, and they were killed and surviving worms were recovered 13 or 14 days after treatment. Against the ivermectin resistant strain, ivermectin did not significantly reduce the egg count or the numbers of adult H contortus; however, both nemadectin and moxidectin reduced the nematode egg counts and the numbers of H contortus by 99 and 100 per cent, respectively. Against the susceptible strain, all the anthelmintics reduced the egg counts by 100 per cent as early as four days after treatment and reduced the numbers of susceptible H contortus by 100 per cent. No adverse reactions to any of the drugs were observed. PMID- 1514228 TI - Bacteria found on intravenous catheters removed from horses. PMID- 1514229 TI - Infection of a marmoset with the BSE agent. PMID- 1514230 TI - Restorative dentistry. PMID- 1514231 TI - Drug combination side effects. PMID- 1514232 TI - BVA policy on animal welfare. PMID- 1514233 TI - Dangerous dogs. PMID- 1514234 TI - Responses of newly hatched chicks to inanition. PMID- 1514235 TI - Factors affecting the leukotoxin activity of Fusobacterium necrophorum. AB - The effect of cultural conditions on the production of leukotoxin by biotypes A and B of F. necrophorum was investigated. Biotypes A and B were grown in prereduced, anaerobically sterilized, brain-heart infusion (BHI) broth. The average leukotoxin titer of culture supernatant was 18 times higher from biotype A strains than from biotype B strains. Leukotoxin activity peaked during the late log and early-stationary phases of growth, then declined precipitously in both biotypes. F. necrophorum biotype A was grown in different media (BHI, liver infusion, and Eugon broths), at various pH (6.6, 7.3, 7.7, and 8.2), incubation temperatures (30, 35, 39, and 43 degrees C), redox potentials (-352 to +375 mV), and iron concentrations (less than 0.2, 4.2, 42.1, and 361.4 microM). Anaerobic BHI broth with pH from 6.6 to 7.7 at 39 degrees C incubation temperature supported maximal F. necrophorum growth and leukotoxin production. The optimum redox potential for F. necrophorum growth was in the range of -230 to -280 mV. However, the presence of titanium III citrate or dithiothreitol (7.78 mM) in the medium decreased (P less than 0.05) the leukotoxicity of F. necrophorum. Low iron concentration (less than 0.2 microM) decreased (P less than 0.05) growth rate but not leukotoxin activity of F. necrophorum, whereas high iron concentration inhibited the leukotoxin activity. PMID- 1514236 TI - Efficacy of a trivalent Haemophilus paragallinarum vaccine compared to bivalent vaccines. AB - The efficacy of a trivalent oil-adjuvant Coryza vaccine containing serotypes A, B and C of Haemophilus paragallinarum has been compared with that of a bivalent oil adjuvant Coryza vaccine containing serotypes A and C and that of a commercially available, bivalent A1(OH)3-potentiated vaccine, containing types A and C. The trivalent vaccine, given at 10 and 17 weeks of age, provided the best protection. Even at 55 weeks after booster vaccination, chickens were still significantly protected, following severe challenge with either of the three serotypes of Haemophilus paragallinarum. Both bivalent vaccines did not protect against type B challenge. Furthermore the oil-adjuvant vaccines induced higher HI-A titers, which correlate with protection, compared to the A1(OH)3-potentiated vaccine. The results show that type B strains are pathogenic and constitute a distinct immunotype and thus a Coryza vaccine should contain three serotypes to obtain a broader protection against all serotypes. PMID- 1514237 TI - Plasmid profile analysis, phage typing, and antibiotic sensitivity of Salmonella dublin from clinical isolates in the United States. AB - One hundred clinical isolates of Salmonella choleraesuis subsp. choleraesuis serovar dublin (Salmonella dublin) were examined for phage sensitivity, antibiotic resistance patterns, and plasmid content. Computer analysis of the lysis patterns observed by using 27 typing phages divided the S. dublin isolates into 26 groups. One lytic pattern (Designated pattern 16) contained 52% of the isolates examined whereas 16 isolates had unique patterns, and nine patterns had fewer than ten members. Although 14 antibiotic resistance patterns were observed among the 100 isolates, 79% of the isolates grouped in three major patterns. Seven plasmid groups were identified and designated A-G based on the large plasmids found in the isolates. Of the 100 isolates, 28 contained the plasmid profile of Group A, 28 were Group B, 7 were Group C, 34 were Group D, and 1 isolate each was observed in Groups E, F, and G. The strong association between antibiotic resistance pattern and plasmid type suggest that the drug resistance genes are plasmid borne. PMID- 1514238 TI - Relationship between the immune response of sheep and the population dynamics of bacteria isolated from fleecerot lesions. AB - In sheep wetted by rain, proliferation of bacteria in the skin-fleece microenvironment invariably discolours the fleece and causes a dermatitic condition known as fleecerot. The changes in population dynamics of fleece bacteria were analysed by carrying out skin washings at randomly selected sites on the back of sheep before, and at 48 h and 96 h after exposure to rain. Gram positive rods belonging to Bacillus species (10(2)-10(4) cfu/cm2) predominated in dry fleece. Gram-positive cocci (e.g. Micrococcus and Staphylococcus species) as well as Gram-negative rods (pseudomonads) were also present but in lower abundance (less than 10(2) cfu/cm2). Fleece bacterial populations generally increased in numbers during the first 24-48 h of wetting. By 96 h however, skin washings showed a preponderance of Pseudomonas aeruginosa (10(4)-10(6) cfu/cm2) and to a lesser extent, pigmented Micrococcus species. Growth of fleece bacteria was associated with a characteristic green or yellow/orange staining of fleece. Fewer species of bacteria were isolated from sheep showing green staining while those animals with yellow/orange discolourations appeared to have a more mixed microflora composition. The predominance of P. aeruginosa in the wet fleece of sheep displaying either green or yellow/orange bacterial stain, was accompanied by a significant serological response against this species. Since skin bacteria have never been observed to penetrate cutaneously in skin sections biopsied from fleecerot sites, it must be concluded that the sheep skin is sensitized by continuous exposure to antigens that are associated with or released by P. aeruginosa. PMID- 1514239 TI - The bactericidal effect of N-acetyl-beta-D-glucosaminidase on bacteria. AB - The bactericidal activity of N-acetyl-beta-D-glucosaminidase (NAGase) on some of the potential bacterial pathogens of the cow was determined. NAGase treatment significantly decreased the mean log10 number of Actinomyces pyogenes (P less than 0.01) and Staphylococcus aureus (P less than 0.05) after 2 and 4 hours of incubation at 37 degrees C. Similarly NAGase treatment significantly (P less than 0.05) reduced the mean log10 number of Streptococcus agalactiae and Pseudomonas aeruginosa after 4 hours incubation at 37 degrees C. NAGase did not reduce the numbers of Escherichia coli or Enterobacter aerogenes after either 2 or 4 hours incubation. Since NAGase and presumably other lysosomal enzymes are free on normal mucosal surfaces such as the uterus it is suggested that this direct bactericidal activity may be an important component of the normal defense mechanisms. PMID- 1514240 TI - Immunity to Toxocara vitulorum repeated infections in a rabbit model. AB - Eleven rabbits were infected with 10 embryonated eggs of Toxocara vitulorum per g body weight on Days 0, 35 and 72. Embryonated eggs and larvae were enumerated in feces on Days 1-3 after each infection. Two rabbits were killed and larvae were enumerated in small intestine, liver, lungs, skeletal muscles, heart, kidney, brain, eye, uterus, and mammary glands on Days 5, 15, 30, 65 and 101. Serum was obtained on Days 0, 5, 15, 30, 42, 50, 65, 78, 86 and 101 to perform enzyme linked immunosorbent assays (ELISAs) and Western blots against an extract of embryonated eggs. Between 4 and 10% of the administered parasites, almost all embryonated eggs, were found in the feces after the first or second infection, but 32% (27% of them larvae) after the third. Yields of tissue parasites were 4.1% of the administered dose on Day 5, 2% on Day 15, and 0.8% on Day 30 of the first infection, 0.1% on Day 30 of the second infection, and 0.06% on Day 30 of the third. Larvae were found only in liver, lungs and muscle, including heart. Larva content declined steadily in liver and lungs from Day 5 to 30 of the first infection, was absent in the liver at Day 30 of the second, and in both organs at Day 30 of the third. Muscle larva content increased from Day 15 to 30 of the first infection, and persisted throughout the third infection. Production of IgM antibody was minimal, IgG and the sum of IgMGA antibodies increased slightly or moderately after the first and second infections, but dramatically after the third. Western blots revealed the first antigens (12) by Day 15 of the first infection. Their total number increased with time and number of infections, but some antigens disappeared, whereas new antigens appeared in the course of the observations. Four antigens (32,500-41,000 mol.wt.) may be related to protection. Comparison of the Western blot patterns of two rabbits showed differences in the antigens, recognizable for each rabbit. PMID- 1514241 TI - Modulation of calf immune responses by Ostertagia ostertagi: the effect of diet during trickle infection. AB - The effects of Ostertagia ostertagi infection and diet on antibody responses to O. ostertagi third stage larval (L3) antigen and to an unrelated antigen, Keyhole Limpet Haemocyanin (KLH) were determined in calves experimentally infected with 3000 L3 on alternate days for 6 weeks. Calves were given one of two diets, and were either infected or not infected with O. ostertagi L3. The diets were either high (H) or low (L) in protein/energy and were within the range of normal husbandry practice in the UK. Both IgG1 and IgG2, but not IgA, responses to L3 antigen were increased in the L-diet compared with the H-diet. IgA responses to L3 antigen were not affected by dietary treatment. The effects of diet and infection on anti-KLH IgG1 were independent of each other; IgG1 anti-KLH responses were decreased by infection and by the L-diet compared with the H-diet. The data suggest that there is a strong interrelationship between diet and immunity during nematode infections. PMID- 1514242 TI - Phenotyping of lymphocyte subsets in the vascular and epithelial lesions of a cow with malignant catarrhal fever. AB - Surface marker analysis of lymphoid cells infiltrating the vascular and epithelial lesions of a cow with malignant catarrhal fever (MCF) was conducted by immunohistochemistry using ten monoclonal antibodies. The majority of lymphoid cells in these lesions had BoCD8, BoCD6 or BoCD2, but they rarely possessed N cell (BoCD5+/BoCD4-/BoCD8-, non-T non-B) markers. Similar reactivity was seen in lymphoid cells of perivascular infiltrates in the liver, heart and brain, and in T-dependent areas of lymph nodes. These results suggest involvement of cytotoxic T-lymphocytes in the pathogenesis of MCF. PMID- 1514243 TI - Flow and image cytometric study of pancreatic neuroendocrine tumours: frequent DNA aneuploidy and an association with the clinical outcome. AB - Eighteen pancreatic neuroendocrine (NE) tumours were analysed for nuclear DNA content by image cytometry (ICM) and flow cytometry (FCM). The DNA indices (DIs) obtained by ICM were somewhat higher than those obtained by FCM, but a major disagreement was present only in 1 case. Thirteen patients had been followed up at least for 6 years after the diagnosis or until death. At 6 years of follow-up all 4 patients with a tumour with a DI greater than or equal to 1.8 by ICM had died from their NE tumour or had metastatic disease, whereas all 9 patients with a smaller DI had no evidence of the disease (P = 0.001). The DIs calculated from the FCM data also correlated well with the final outcome (P = 0.01). A high incidence of DNA aneuploidy was found by both methods in histologically and clinically benign NE tumours; 12 (67%) were DNA aneuploid by FCM and 16 (89%) by ICM. It is concluded that pancreatic NE tumours are frequently DNA aneuploid, and both cytometric DNA methods give prognostic information in these tumours. The presence of DNA aneuploidy should not be considered as a sign of malignant behaviour in pancreatic NE tumours, whereas a large DI is associated with poor prognosis. PMID- 1514244 TI - Intimal fibrosis (phlebosclerosis) in the saphenous vein of the lower limb: a quantitative analysis. AB - The influence of pre-existing phlebosclerosis on the patency rate of aorto coronary bypasses is uncertain. To examine this influence, extensive quantitative histological investigations of the intimal thickness of the left saphenous vein were made in 30 cases. In almost all veins the intima was thickened by collagen and elastic fibres as well as by fusiform cells which were assumed to be smooth muscle cells. The innermost layers also contained increased collagen adding to the intimal thickening. Three different methods to measure the intimal thickness were tested morphometrically: planimetric, a four-point method and a so-called method of estimate. The latter is the most time-saving and effective method. The average intimal thickness showed considerable deviations, but the intimal thickness in individual veins did not deviate greatly. As a rule, a specimen with an intimal thickness of less than 100 microns belonged to a vein with mild or moderate intimal thickening, but specimens with an average intimal thickness of 100-250 microns usually derived from a vein with moderate or pronounced intimal fibrosis. However, extreme values allowed a more precise statement to be made. A specimen with a nonsclerotic intima suggested at best a mild intimal fibrosis of the vein in the lower limb, whereas a specimen with marked intimal thickening derived from a vein with severe phlebosclerosis. PMID- 1514245 TI - Argyrophilic nucleolar organizer region counts in multiple myeloma: a histopathological study on bone marrow trephine biopsies. AB - Argyrophilic nucleolar organizer region (Ag-NOR) analysis was performed on bone marrow biopsies from 90 patients with multiple myeloma (MM) at presentation. The pattern of AgNOR expression and its relationship to histological features were evaluated. The mean AgNOR number per plasma cell was directly correlated with the degree of MM differentiation (3.18 for G1, 4.36 for G2, 6.13 for G3; P less than 0.0001), with the percentage of bone marrow plasma cells (BMPC%) (3.06 for BMPC% less than or equal to 20, 4.28 for BMPC% 21-50, 5.14 for BMPC% greater than 50; P less than 0.0001), with the pattern of medullary involvement (3.63 for interstitial, 4.44 for nodular, 5.17 for diffuse involvement; P less than 0.001) and with medullary fibrosis (5.23 for cases with fibrosis, 4.29 for cases without fibrosis; P less than 0.05). The plasma cells of G1 MM showed 2-3 large AgNORs, tightly grouped in a central nuclear cluster; those of G2 MM showed a central nuclear cluster composed of 4-5 medium-size dots and/or two clusters of 2-3 dots; the G3 MM plasma cells showed many small dots scattered in the nucleolus or dispersed in the nucleus. Our results indicate the diagnostic value of AgNOR analysis in MM and suggest the use of this method for identifying clones of atypical plasma cells with different proliferative activity in bone marrow biopsies. It allows simultaneous evaluation of the morphology and kinetics of MM cells in routinely fixed, decalcified, paraffin-embedded material. PMID- 1514247 TI - Nodular regenerative hyperplasia of the liver associated with metastases of pancreatic endocrine tumour: report of two autopsy cases. AB - Two autopsy cases with multiple hepatic metastases of pancreatic endocrine tumours and nodular regenerative hyperplasia of the liver (NRH) are reported. The tumour cells were positive for glucagon, insulin, gastrin and vasoactive intestinal polypeptide immunohistochemically and the serum gastrin was elevated in one case. In the other, tumour cells were positive for insulin. Controls failed to show NRH in the non-metastatic part of 35 autopsies of livers with multiple hepatic metastases. A combination of hepatotrophic hormonal factor(s) and disturbed hepatic circulation associated with hepatic metastases may be important in the development of NRH. PMID- 1514246 TI - Immunohistochemical evaluation of E-cadherin adhesion molecule expression in human gastric cancer. AB - E-cadherin (ECD) is one of subclasses of the cadherin family which plays a major role in the maintenance of intercellular adhesion in epithelial tissues. An immunohistochemical study of ECD expression was performed on gastric adenocarcinoma from 103 patients using our monoclonal antibody for human ECD (HECD-1). ECD was strongly expressed in normal gastric epithelium without exception; however, various staining patterns were observed in cancer tissues. The frequency of tumours with preserved ECD expression (Pre-type) and reduced ECD expression (Rd-type) was 42% and 58% respectively. Tumours with a high frequency of Rd-type expression particularly included: undifferentiated tumours (85%, 46/54), Borrmann's type 4 (90%, 9/10), tumours larger than 2.6 cm in diameter (65%, 53/81), tumours invading beyond the subserosa layer (78%, 46/59), and tumours with infiltrative growth (87%, 41/47). Furthermore, the frequency of Rd type expression in cases with peritoneal dissemination (82%, 9/11) or lymph node metastasis (73%, 43/59) was significantly higher than that in cases without dissemination or metastasis. These results suggest that ECD might play a key role in the genesis of histological differentiation, and that the reduction of ECD expression may affect the mode of invasion and metastasis of human gastric cancer cells. PMID- 1514248 TI - Fibrosarcoma in association with a total knee joint prosthesis. AB - A case of fibrosarcoma of the proximal tibia, arising at the site of a cemented Richards total knee joint replacement with cobalt chrome alloy is reported. The patient, an 80-year-old man, received the endoprosthesis because of osteoarthritis of the knee 4 years ago. The literature on malignant tumours occurring in association with endoprostheses is summarized and briefly discussed. PMID- 1514249 TI - Immunohistological detection of tissue factor in normal and abnormal human mammary glands using monoclonal antibodies. AB - Tissue factor (TF) is the primary cell-bound initiator of the coagulation protease cascade. The cytological distribution of TF in various tissues may be described on the basis of immunohistochemistry with epitope-defined monoclonal antibodies and the extravascular distribution of TF apparently represents a haemostatic envelope ready to activate coagulation when vascular integrity is disrupted. The present study localized TF in human breast cancer tissues when compared with normal breast gland tissues and benign disorders of the mammary gland. By use of a cocktail of three epitope-defined monoclonal antibodies, TF was detected only in the myoepithelia of the resting breast gland. In proliferating disorders like fibrocystic disease or in fibroadenomas, both myoepithelia and luminal epithelia showed TF expression. Of 115 breast cancers 93 reacted with anti-TF, in an inhomogeneous manner in terms of intensity and number of positive cells. There was a tendency for more positive and intensely stained cells to be found in well-differentiated structures such as tubules. Invasive ductal carcinomas exhibiting more positive and more strongly stained cells were less commonly metastatic to lymph nodes when compared with the tumours with no detectable or very low TF immunostaining. A semi-quantitatively recorded score of TF immunostaining correlated with the procoagulatory activity measured (7 fibroadenomas and 24 carcinomas). The results of this study suggest that proliferation and differentiation of the mammary gland is associated with enhanced TF expression in the epithelia which are negative for TF staining in the resting gland. Malignant growth is characterized by randomly expressed epithelial TF, which expression is enhanced and more frequent in well-differentiated tumour cells. PMID- 1514250 TI - Carcinoma-associated perisinusoidal laminin may signal tumour cell metastasis to the liver. AB - The perisinusoidal space of the liver shows extensive modulation of the extracellular matrix in response to various pathological conditions. We studied perisinusoidal laminin expression immunohistochemically using polyclonal and monoclonal antibodies in 110 human liver specimens obtained at autopsy. In normal adult liver the perisinusoidal spaces contained only minimal amounts of immunoreactive laminin. In 86% of patients dying from cancer with liver metastasis, however, a distinct increase in the amount of perisinusoidal laminin could be demonstrated. The perisinusoidal space also contained laminin in cancer patients without liver metastasis. In 3 cases of leukaemia sinusoids were laminin negative. In cirrhosis and chronic passive congestion there was, as expected, laminin immunoreactivity in the perisinusoidal space. The results obtained using polyclonal antibodies against laminin were confirmed using chain-specific monoclonal antibodies against B2 laminin. In an ex vivo assay, viable tumour cells (Panc-1 and clone A) were found to bind with remarkable specificity to frozen sections of liver tissue containing perisinusoidal laminin as opposed to liver tissues without laminin. We suggest that this perisinusoidal laminin may directly on indirectly mediate tumour cell metastasis to the liver. PMID- 1514251 TI - [Separate nutrition: optimization of the work of body systems?]. PMID- 1514252 TI - [Endocrine regulation of carbohydrate metabolism in the newborn depending on the type of feeding]. PMID- 1514253 TI - [Non-enzymatic glycosylation of dietary proteins by glucose and fructose]. AB - Preliminary evaluation of glucose and fructose as glycosylation agents of some animal and vegetable food proteins has been presented. The study was conducted using the method of radioactive indicators. It has been shown that fructose binds proteins to a higher degree than glucose, and it can make for increasing glucose glycosylating activity in their combination in the product. PMID- 1514254 TI - [Adaptation of rats to unusual protein products during transition to definitive nutrition]. AB - The authors studied the adaptation of initial and final links of the proteolytic chain, and intermediate nitrogen metabolism, to unusual products--protein concentrate from yeast-saccharomyces and anchovy. A number of enzymes in the organs-producers were found to be activated due to intensification of a limited proteolytic reaction. It was established that the changes in the functioning of the proteolytic stage of the digestive-transport conveyor led to shifts in the amino-acid pool in the blood serum of experimental animals. PMID- 1514255 TI - [Effects of polyunsaturated fatty acids in the ration on the structure of peripheral lymphoid organs, immunological parameters and nonspecific resistance of rats]. AB - It has been established that the fatty component of the ration, with the rest ingredients being unchanged, alters the immunologic status of the body. When fatty portion of the ration was substituted for sunflower oil (omega 6) active macrophage-plasmocytic reaction in the lymphoid organs, elevation of the humoral immunity parameters and suppression of the T-cell system were recorded. The reaction to immunization was less pronounced when equal ratios of sunflower and ichtyenic oils were used. When the fatty component of the ration was completely substituted for ichtyenic oil, a decrease in T-lymphocyte number and focal necrotic changes in the lymphoid organs were observed. The fatty component of the rations used produced no significant effect on the bactericidal activity of the blood serum. PMID- 1514256 TI - [Effects of pectin in the ration on cholesterol metabolism in rats]. AB - Inclusion into the ration of 2.5 or 5% of apple pectin during 20 days did not significantly change the blood serum composition: cholesterol content decreased as compared to the control, the number of general bile acids increased. When apple pectin was added to the animals' ration containing egg powder, the amount of cholesterol excreted with feces increased depending on pectin content in the food. PMID- 1514257 TI - [Effects of polyunsaturated fatty acids on Krebs cycle in the rat kidney in chronic phosphorus intoxication]. AB - The investigation of Krebs cycle state in kidney homogenates of August rats subjected to oral intoxication with oil solution of yellow phosphorus in a dose of 0.3 mg/kg, has shown that under conditions of balanced nutrition the activity of NAD-dependent isocitrate dehydrogenase, succinate dehydrogenase and accumulation of the substrate fund of the cycle decreased 3.5-fold as compared to the control. The addition of polyunsaturated fatty acids to the ration produced a positive effect on Krebs cycle state: dehydrogenase activity was not significantly changed, accumulation of Krebs cycle substrate was two-fold lower. However, this ration did not completely abolish the toxic action of yellow phosphorus on Krebs cycle. PMID- 1514258 TI - [A comparative study of the effects of vegetable oils and cholesterol on enzymes of the mouth and jejunal mucosae]. AB - The influence of sunflower and olive oils and their combination with cholesterol on the activity of lysosomal hydrolases and lipid peroxidation (LPO) in the mucosa of the mouth and jejunum was studied. It was shown that in the presence of cholesterol in the oral mucosa the activity of N-acetylhexosaminidase increased and there was a tendency to decreasing cathepsin D and acetyl esterase activity, and LPO processes were found to be suppressed. Cathepsin D and B activities in the jejunum mucosa increased in response to cholesterol administration. The changes revealed in the activities of N-acetylhexosaminidase, proteinase, acetyl esterase, catalase and glutathione peroxidase in the oral mucosa, as well as cathepsins in the jejunum depend on the character of lipid additives. PMID- 1514259 TI - [Effects of diverse technological methods of baking wheat bread on the rate of carbohydrate digestion]. PMID- 1514260 TI - [Prospects of the use of beta-carotene enriched food products in the prevention and therapy of radiation injuries]. AB - Radio-protective effectiveness of short-term (19 and 4 h before, 4 and 24 h after irradiation), long-term (3 times/week during 30 days after irradiation) and delayed (1 or 2 days after irradiation) enrichment with crystallized beta carotene, in single doses of 0.1, 1.0 or 5.0 mg was evaluated in experimental acute external gamma-irradiation (0.029 Gy/sec) within the range of absorbed doses 9--6 Gy. The results obtained have permitted the authors to recommend the ration enriched with carotinoid for prevention and therapy of acute radiation injuries. PMID- 1514262 TI - [Structure of the consumption of baked goods in the Kemerovo Region and improvement of their nutritional value]. PMID- 1514261 TI - [Standards of physiological requirements and nutritional substances and energy for various groups of the USSR population]. PMID- 1514263 TI - [Characteristics of fatty acid composition of pine kernels in Siberia and Far East]. PMID- 1514264 TI - [Effects of storage conditions and thermal treatment on phospholipids of Pacific squids]. PMID- 1514265 TI - [Balancing of food substances in domestic and hospital rations (diet No. 15)]. PMID- 1514266 TI - [New approaches to the treatment of obesity--"school for the fat"]. PMID- 1514267 TI - [Use of hypoallergenic diet and specialized products in the treatment of patients with food allergy]. PMID- 1514268 TI - [Nutritional and vitamin status of preschool children]. AB - The actual nutrition of children in nurseries taking into account the losses of food substances during food cooking and realization is inadequate to the current physiological standards for all food substances, especially, with respect to vitamins and mineral elements. This inadequacy has been proved by the laboratory and clinical parameters of vitamin status of children. In the winter-summer period when vitamin deficiency in the rations is most pronounced, deviations in the content of vitamins and their metabolites in the blood and urine, as well as the incidence of hypovitaminosis symptoms in children are more frequently recorded and in the most pronounced form. PMID- 1514269 TI - [Effects of vitamin administration on the parameters of mental capacity of junior school children]. PMID- 1514270 TI - [A comparative study of vitamin status of children 5-6 years of age in different children's institutions]. AB - A total of 205 children were under observation (48 children aged 1.5-3 years in a Baby's Home--spring, 1987; 85 children aged 3-6 years in nurseries with 24-hour stay--spring, 1987; 77 children aged 3-6 years in a Children's Home--spring, 1989). As a result of nutrition reorganization in these institutions vitamin consumption increased due to a more rational selection of food products and the vitamin status of children improved. This was more expressed in vitamin excretion levels, than in the incidence rate of microsymptoms of vitamin deficiency. Additional vitaminization with multivitamin compounds is necessary to eliminate vitamin deficiency in preschool children of isolated institutions. PMID- 1514271 TI - [Evaluation of the effectiveness of prophylactic vitamin administration to school children in Moscow]. AB - The influence of prophylactic vitamin administration to schoolchildren in Moscow was studied basing on the parameters of their providing with vitamins, physical development and health. It was established that as a result of prophylactic vitamin administration of "Undevitum" during 6 months the morbidity rate (especially, of acute respiratory diseases) decreased that produced a definite economic effect. The prophylactic vitamin administration to schoolchildren in the winter-spring period has been recommended. PMID- 1514272 TI - [Effects of prophylactic vitamin administration to Tallin's schoolchildren on their health and physical development]. AB - Data are presented on the influence of prophylactic vitamin administration to schoolchildren in two schools on their health. The morbidity rate significantly decreased, the levels of lysozyme in the saliva, hemoglobin in the blood and total protein in the blood serum rose in the children who received multivitamin "Undevitum" during 5-7 months, as compared to those who were not given the vitamins. Vitamin administration did not influence the physical development of schoolchildren. PMID- 1514273 TI - [Effects of prophylactic vitamin administration on psychoemotional stress tolerance of senior schoolchildren]. PMID- 1514274 TI - [Dynamics of mental and physical capacities of Moscow's schoolchildren administered vitamins]. AB - Mental and physical capacities were studied in schoolchildren aged 6-10, 11-13 and 14-17 years in the autumn-spring period during vitamin administration of "Undevitum". The six-month vitamin administration produced a positive effect on the functional state of the schoolchildren that was expressed in the improvement of their mental and physical capacity parameters. PMID- 1514275 TI - [Biochemical indicators of vitamin provision to Orenburg's schoolchildren and effectiveness of prophylactic vitamin administration]. AB - The study of providing with vitamins of schoolchildren in Orenburg conducted in the spring of 1985-1986 has revealed decreased content of ascorbic acid in 92%, vitamin E in 62%, vitamin A in 39%, folic acid in 38%, vitamin B12 in 14% of the children, the incidence rate of vitamin deficiency among the children in the senior forms was higher as compared to that in the junior forms and in boys it was more frequent than in girls. Additional intake of multivitamin "Undevitum" by schoolchildren during 2-4 months led to a significant improvement of their providing with vitamins that was expressed in normal vitamin levels and elimination of cases of deep vitamin deficiency. PMID- 1514276 TI - [Effects of prophylactic vitamin administration of physical fitness of schoolchildren in the Arctic Regions]. AB - The effectiveness of prophylactic vitamin administration to schoolchildren in the Arctic region was evaluated in the biochemical investigation of schoolchildren by the assay of vitamins C, A, E, B1, B2, B6, B12 and folic acid in their blood serum before and after "Undevitum" intake. Deficiency of a number of vitamins was detected. It was shown that regular consumption of multivitamin "Undevitum" produced a positive effect on the parameters of their physical activity, the highest effect was observed in children with the normotensive reaction to loading, and it was less expressed in those with pathological hemodynamic reactions to the loading. PMID- 1514277 TI - [Effects of the preparation Undevit on the indicators of vitamin provision of Norilsk's schoolchildren]. AB - The effect of the prophylactic use of multivitamin "Undevitum" on parameters of vitamin providing of schoolchildren in Norilsk was studied. The results of the investigation showed a positive effect of the prophylactic vitamin administration on providing with vitamins of schoolchildren in Norilsk and proved the necessity of conducting mass vitamin administration to schoolchildren. PMID- 1514278 TI - [Experience in prophylactic vitamin administration to schoolchildren in Kemerovo]. PMID- 1514279 TI - [Providing with vitamins of different population groups in Sverdlovsk]. AB - The investigation on providing with vitamins of varying population groups: preschool children, schoolchildren, students of trade schools and higher schools, workers and employees was conducted in Sverdlovsk. Low levels of vitamin C were detected in the blood of 40-92%, folic acid--in 10-76%, vitamin A--in 4-28%, carotene--in 8-60%, tocopherol--in 4-50% of the examinees. Vitamin B1 deficiency was noted in 36-68%, vitamin B2--in 17-71%. The highest deficiency of ascorbic acid was recorded in workers and students of trade schools and higher schools, of folic acid--in workers and adolescents of 15-18 years, of vitamins B1, E, A and carotene--in children and adolescents, vitamin B1--in employees. The mass character of vitamin deficiencies and their negative effects on the health of the population have necessitated broad-scale prophylactic measures: production of vitamin-enriched foods, regular use of multivitamins. PMID- 1514280 TI - [Effectiveness of therapeutic-prophylactic vitamin administration to workers at the steel smelting plant of the Karaganda Metallurgy Concern]. PMID- 1514281 TI - [Providing with vitamins of river transport workers of the Western and Eastern Siberia and oil men of the Tyumen Region]. AB - The investigation of providing with vitamins of river transport workers in Western and Eastern Siberia and of oil men in the Tyumen Region conducted in the summer period of 1984-1986 has revealed significant deficiencies of vitamins C, E, B1, B2, B6, A and carotene in them. Vitamin administration to the workers with "Undevitum" resulted in a significant improvement of their vitamin status that was expressed in elevation of their biochemical parameters and in diminution of the percentage of subjects with vitamin deficiencies. PMID- 1514282 TI - Giant cell tumor of the small bones of the hands and feet: metatarsal giant cell tumor. AB - Giant cell tumors (GCTs) of the small bones of the hands and feet are very rare. The prevalence of hand involvement is 5.8 percent and of the feet is 3.6 percent. When GCTs occur in these locations, they appear to represent a distinctive more aggressive form of tumor. They occur more often in a younger patient population, are more commonly multifocal, and are associated with higher risks for local recurrence and pulmonary metastasis. This article presents a rare case of GCT of the metatarsal bone and discusses the presentation, distinctive characteristics and treatment of this tumor when it occurs in these locations. PMID- 1514283 TI - Treatment of giant intracranial aneurysm with carotid ligation, saphenous vein bypass graft. AB - Giant intracranial aneurysms pose difficult problems for neurosurgeons. This article describes the technique of extracranial-intracranial saphenous vein bypass graft and carotid artery ligation as treatment to remove a giant intracranial aneurysm. PMID- 1514284 TI - Exercise testing for the primary care physician. AB - In the primary care setting, exercise testing is frequently used to evaluate patients with known or suspected coronary artery disease. Appropriate utilization requires knowledge of the indications as well as the contraindications and interpretation of the variables generated by the test. While ST segment changes are widely regarded as the most important variable generated by the exercise test, other variables including ventricular arrhythmias, blood pressure response, ischemic symptoms, workload, and exercise capacity are also important and useful in interpretation. Consideration of the question being addressed, the clinical context, and the test adequacy are all important for proper interpretation. Interpretation concerning both diagnostic and prognostic questions should employ principles of both the categorical and probability approaches. PMID- 1514285 TI - Strange timing. PMID- 1514286 TI - Surgery in Salzburg. Festschrift for Oskar Boeckl. PMID- 1514287 TI - [Experiences with total parathyroidectomy and autotransplantation of intraoperatively selected parathyroid tissue in reactive renal hyperparathyroidism]. AB - Surgery is indicated in cases of therapy-resistant reactive renal hyperparathyroidism with clinical symptoms and signs. The method of choice is total parathyroidectomy, with autotransplantation of parathyroid tissue into the forearm musculature. Twenty-two patients were parathyroidectomized. In 19 cases the intraoperative selection of tissue for autotransplantation was made by means of a stereoscopic magnifying glass. With one exception, only fragments of type 1a glands and type 1a-like areas obtained from type 2 glands were transplanted. In 18 of the 22 cases parathyroid hormone levels decreased from 1131 +/- 657 preoperatively to 87 +/- 53 pg/ml postoperatively. In 4 patients with postoperative values over 200 pg/ml a transplant-related recurrence of hyperparathyroidism or a remaining 5th gland in the cervical region was suspected. In all 22 patients serum calcium, as well as alkaline phosphatase levels returned to normal and the clinical signs of hyperparathyroidism disappeared. PMID- 1514288 TI - [Technique of recurrent laryngeal nerve exposure within the scope of interventions of the thyroid gland]. AB - In anatomical preparations performed during autopsy we developed a well-defined approach for the identification of the recurrent laryngeal nerve during surgery on the thyroid gland. The principle of this concept is to visualize the nerve near the branching of the inferior thyroid artery, where it shows a 30 degree angle to the trachea in a direction running from caudal lateral to cranial medial and lies in front of, behind, or between the branches of the artery. This preparation mode has been prospectively performed in 100 patients undergoing thyroid surgery. In 159 (= 97.6%) sides of the neck out of 163 we identified the nerve at the typical site. The topographical relation of the recurrent nerve to the inferior thyroid artery revealed the following differences for the right and left side of the neck: On the right side the nerve was found to be behind in 48%, in front in 33% and between the branches of the artery in 15% of cases. In contrast, on the left side the nerve was found to be dorsal in 53%, ventral in 23% and between the branches in 23%. Of 163 nerves at risk we observed primary nerve palsy in 2 cases (1.2%), and a definitive palsy rate of 0.6% at the 3-month follow-up. In conclusion, we recommend the described approach for the identification of the recurrent laryngeal nerve during thyroid surgery whenever complete mobilisation of the thyroid lobe (e.g. thyroidectomy, lobectomy, resection of retrotracheal adenomas) is necessary. PMID- 1514289 TI - [Laparoastoma (open packing) in the treatment concept of infected pancreatic necroses]. AB - Out of 284 patients with acute pancreatitis 73 (26%) had pancreas necrosis. Of these 73 cases 43 patients with infected pancreas necrosis were treated surgically, whereas conservative treatment proved successful in the remaining 30 cases with so-called sterile necrosis. Our interdisciplinary treatment combined delayed surgery for the better demarcation of the necrotic tissue, with extended intensive care therapy and epigastral laparostomy; through this laparostomy surgical revision with necrosectomy and peritoneal lavage was performed daily for 15 (+/- 6) days, necessitating long-term artificial respiration for an average of 15 (4/168) days. The mortality rate in the 43 patients with infected pancreas necrosis amounted to 16.2% (n = 7); none of the patients with sterile necrosis died. In cases of multiple organ failure the mortality rate was significantly higher (30%) than with failure of only one organ system (4.3%). The mortality rate in all cases with pancreas necrosis (n = 73) amounted therefore to 9.5%. Serious complications of laparostomy occurred in 28% (n = 12) of the 43 patients, whereby 8 of these cases were gastrointestinal fistulae, with a fatal outcome in one patient. The overall mortality rate in the total group of 284 patients with acute pancreatitis was 2.8%. PMID- 1514290 TI - [A combined endoscopic surgical treatment concept in acute biliary pancreatitis]. AB - This paper presents the results of a combined endoscopic-surgical approach with management of acute biliary pancreatitis in 91 patients. The diagnosis was always made by means of endoscopic-retrograde cholangiography. Papillary or bile duct stones, or unmistakable signs of previous stone passage, and in exceptional cases flow obstruction due to preiampullary diverticuli were considered criteria for a positive diagnosis. All 91 patients were subjected to endoscopic sphincterotomy with/without stone extraction subsequent to the diagnostic cholangiogram. Endoscopic intervention was performed as soon as possible after admission to hospital, but by 48 hours at the latest. Cholecystectomy was carried out in all patients who were free of risk factors and without previous cholecystectomy, during the disease-free interval. The complication rate of this combined endoscopic-surgical approach amounted to 10.9%; the mortality rate was 3.3%. The achieved results suggest that endoscopic sphincterotomy with stone extraction in the acute phase of biliary pancreatitis is the method of choice in order to interrupt the process of this disease. In combination with the final surgical treatment of gallstone disease by cholecystectomy to avoid recurrences, the prognosis of acute biliary pancreatitis can be significantly improved by using this combined endoscopic-surgical management. PMID- 1514291 TI - [Extracorporeal shock wave treatment of calcium containing gallbladder calculi]. AB - A total of 50 patients--37 female and 13 male--with an average age of 50 +/- 27 years (23-86 years), suffering from rim-calcified gallbladder stones, underwent extracorporeal shock-wave lithotripsy (ESWL), using an ultrasound-guided overhead module of Lithostar Plus (Siemens Company). The total number of stones was 87, with an average diameter of 16 +/- 7 (7-38) mm. 29 patients had a solitary stone, 13 had two and 8 patients three or more stones. All patients received adjunct medication of 10 mg/kg body weight chenodeoxycholic and ursodeoxycholic acid 14 days prior to ESWL as a single bedtime dose. An average number of 5,300 +/- 2,200 shock waves (1,200-15,000) was applied for stone disintegration. The corresponding energy amounted to 750 bar. 29 patients needed one, 21 two or more treatments. After ESWL a variety of clinical abnormalities was observed: flank pain (15%), transient microhaematuria (33%) and transient macrohaematuria (2%). Subsequent to ESWL 5 patients suffered from complications such as biliary obstruction 3 weeks to 9 months after treatment and had to undergo ERCP. Three times endoscopic papillotomy was performed to remove stones from the common bile duct. Up to now 4 patients have undergone cholecystectomy: acute cholecystitis (n = 3), recurrent colicky pain (n = 1). 20 patients have been followed up over a 12 month period; 12 of them are completely free of stones and fragments. PMID- 1514292 TI - [Reconstruction-plasty of iatrogenic choledochal stenoses using human pericardium. An experimental study in the domestic pig]. AB - The effect of human pericardial patch plastic for reconstruction of iatrogenic common bile duct stenosis was investigated in experiments performed in pigs. All patches (n = 8) were overgrown with immature biliary epithelium detectable on light and electron microscopy within 6 weeks. No restenosis nor any fistula developed during this observation period. Liver function tests, especially bilirubin, were not suitable parameters for the detection of biliary obstruction (preoperative value 0.38 +/- 0.09 mg/dl; 1 week after subtotal stenosis 3.36 +/- 1.53 mg/dl; 2 weeks after subtotal stenosis 1.49 +/- 0.62 mg/dl; 3 weeks after subtotal stenosis 0.50 +/- 0.27 mg/dl; 6 weeks after pericardial patch plastic 0.33 +/- 0.05 mg/dl, mean +/- SD. Ultrasonographic measurement of the common bile duct diameter was the diagnostic method of choice. Preoperative dimension 4.5 +/- 0.5 mm; 1 week after subtotal stenosis 8.5 +/- 2.0 mm; 2 weeks after subtotal stenosis 10.5 +/- 1.8 mm; 3 weeks after subtotal stenosis 14.0 +/- 3.6 mm; 6 weeks after pericardial patch plastic 9.0 +/- 1.6 mm, mean +/- SD. PMID- 1514293 TI - [Autotransplantation of the spleen in rats: development, function and cytokine expression in intra-omental and subcutaneous regeneration]. AB - The implantation of splenic tissue at different implantation sites (intraomental and subcutaneous) into one animal (Lewis rats) results in the development of splenic nodules at both sites. In a quantitative immunohistological analysis of splenic compartments such as red pulp (RP), periarteriolar lymphoid sheaths (PALS), marginal zone (MZ) and follicles (F) the T-cell reduction was related to the T(helper) cells in the MZ and T(supp/cyt) cells in the PALS. In contrast, the cell density of B cells and ED-1+ macrophages in the PALS and T(supp/cyt) cells in the MZ was increased. Significant differences between the implantation sites were restricted to CD5+ cells (thymocytes and T cells) in the MZ and OX-33+ cells (B cells with LCAB antigen) in the PALS. The reorganisation of the compartments of subcutaneous implants showed a delay of one week as compared with omental ones. Functional assays like haemolytic plaque assay, mitogen stimulation and mixed lymphocyte assay elicited an analogous delay of the functional maturation of IgM-positive B cells, a reduced proliferation of both transplant groups after pokeweed mitogen (PWM) stimulation, a decreased response after lipopolysaccharide (LPS) stimulation in solely subcutaneous replants and no differences concerning the mitogens concanavalin A (ConA) and phytohaemagglutinin (PHA). Both transplant groups showed a significantly reduced allogeneic response. The results of the functional analysis and the abnormal mRNA expression of Il-5, Il-6 (Interleukin 5 and 6), GMCSF (Granulocyte-Macrophage-Colony-Stimulation-Factor) and IFN-gamma (Interferon gamma) in subcutaneous replants indicate subtle molecular alterations (independent of a spleen-like immunoarchitecture) at this site.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1514294 TI - [Effects of surgical therapy of extreme obesity on physical and psychological outcome]. AB - More than 400 patients with morbid obesity were treated surgically in our unit over the past 18 years. Three different methods (intestinal bypass, bilio intestinal shunt and vertical banded gastroplasty) were used. In order to assess any postoperative increase in life quality and to compare the three different techniques, 25 matched patients from each group were followed up and the findings compared with a group of non-operated morbidly obese persons. Psychological tests were also supplied. Irrespective of the technique performed a significant increase in quality of life was obtained in 75% of the cases. PMID- 1514295 TI - [Prevention and treatment of postoperative fistulae--new indications for fibrin gluing]. AB - The additional sealing of bronchial and gastrointestinal sutures and anastomoses, respectively, by means of fibrin sealant helped to significantly reduce the postoperative dehiscence rate; this rate amounted to 3.6% for additionally sealed bronchus stump occlusions and to 4.2% in gastrointestinal operations, whereby naturally in emergency abdominal operations the rate was higher (7.7%) than in elective surgery (3.8%). Eight postoperative bronchus stump fistulae and eleven out of the twenty-five gastrointestinal anastomotic dehiscences could be closed using a fibrin clot. Furthermore, fibrin occlusion of the pancreatic duct following Whipple's operation for the protection of the pancreatic-digestive anastomosis (n = 67) has turned out to be a success, since no postoperative pancreatic fistulae occurred, which resulted in the very low mortality rate of 1.5%. One more indication for fibrin sealing was the prevention of postoperative lymph fistulae by additional wound sealing (n = 123) and the fibrin occlusion of these fistulae (n = 18); the postoperative lymph fistulae rate amounted to only 3.3%. All 4 cases, as well as 14 other cases of existing lymph fistulae were healed quickly by instillation of fibrin. These relatively new, partly endoscopic, procedures using fibrin sealing proved to be very successful, because on the one hand postoperative fistulae could be largely avoided and on the other hand they could be treated without further operation. PMID- 1514296 TI - [RU 486--death hides behind this formula]. AB - Today we are faced with a new abortion method: until the 49th day of pregnancy a pregnant woman will loose her child as a consequence of an artificial miscarriage by taking the hormone drug RU 486. It opens a new perspective as a new contraceptive method, an abortion method and a new possibility for family planning in Third World Countries. This pill has been developed and produced by the French chemical company Roussel-Uclaf and is available in France, Great Britain and China. Permission to operate on the German market hinges on 3 conditions: that there is new abortion legislation in Germany, the exclusion of misuse is guaranteed and a representative group requires the application. PMID- 1514297 TI - [Brief definitions of medical ethics concepts. 22. Advance directives]. PMID- 1514298 TI - [Ethical controversy surrounding RU 486: data and arguments]. AB - By RU 486 being synthesized (1980) a pharmacological alternative to surgical methods of abortion has been created. Since 1988 Mifepristone is applied for termination of pregnancies under severe control. Major pros and cons in debates about RU 486 in medical publications are analyzed, their relations to central ethical principles being worked out clearly. As consequences of the analysis of arguments the authors formulate four conditions for the use of Mifepristone as method of abortion which should be considered in further research and practice. PMID- 1514299 TI - [Mifepristone (RU 486)]. AB - The antiprogestin RU 486 converts the early pregnant uterus by increasing the sensitivity of the myometrium to prostaglandin (PG). These effects of antiprogestin have resulted in the development of nonsurgical procedures to abort embryos based on a combination of RU 486 and different PG-analogues administered vaginally or intramuscularly. RU 486 also has a softening effect on the cervix which may be used as pretreatment in second and third trimester abortions. The effects, mode of action, dangers, and the many other postulated clinical implications (like breast cancer, meningioma, ectopic pregnancy, fetal death in utero, induction of labour, initiation and promotion of lactation, endometrial or ovarian cancers, leukemia, Cushing's syndrome, uterine adenomyosis, acute uremia, leiomyosarcoma, hypertension, etc.) are discussed. PMID- 1514300 TI - [Long-term therapy of immune neutropenia with high-dose 7S immunoglobulin in a child]. AB - A 15 month old girl with suspected immune neutropenia was treated with high dose immunoglobulin because of recurrent infections over a period of 9 months. Before therapy her neutrophil counts were below 0.5 G/l. With monthly intravenous immunoglobulin her neutrophils remained above 0.5 G/l with one exception. Even after 9 months the patient responded well to therapy, she did not experience new episodes of infections. We suggest that in case of recurrent infections high dose immunoglobulin therapy should be considered in patients with immune neutropenia before the occurrence of life threatening infections. PMID- 1514301 TI - [Placebo forte: contribution to the demystification of a therapy principle]. AB - Placebo effects are an important component in the success of any therapy. Several forms of placebos exist. Their effects are due to phenomena some of which are difficult to define. They comprise changes in subjective as well as objective variables. Thus they exceed the frequently cited "suggestion". The discriminative use of placebos in therapy can be helpful. PMID- 1514302 TI - [Ultima ratio in the treatment of the terminal form of eclampsia in puerperium]. AB - The described Novocaine blockade of the ganglia in the sympathetic chain which control renal vascular function has closed the fatal gap in the treatment of terminal eclampsia of pregnancy, which has existed up to now. By removing the inhibition of renal function, toxic substances are excreted, thus resolving the vicious circle of generalized vascular spasm, hypertension, and decreased blood supply to the brain, kidneys, liver, and optic fundus. PMID- 1514303 TI - [24-hour blood pressure measurement in normal children and adolescents]. AB - Blood pressure was continuously monitored over 24 h in 33 healthy children and adolescents (18 girls, 15 boys, age 6-17 years) using a portable monitor. The results were compared with European blood pressure centiles for normal children and adolescents. On average, 67% (57-88%, median and quartiles) of the measurements were completed. The day's mean for systolic blood pressure for girls was 0.04 (-0.67-1.00) standard deviations above the mean of the reference group with corresponding body-height, and for diastolic blood pressure, 1.08 (0.50 1.63) standard deviations. The corresponding values for boys were 0.42 (0.09 0.45) for systolic and 1.11 (1.00-1.39) for diastolic blood pressure. Mean systolic blood pressure for girls decreased during the night by 10% (5-13%) compared to the day time measurements, and the diastolic blood pressure decreased overnight by 23% (12-28%). Systolic blood pressure for boys decreased overnight by 8% (6-11.5%), and diastolic blood pressure decreased by 15% (12-19%). PMID- 1514304 TI - [Rhythm analysis of individual 24-hour blood pressure profiles of patients with essential hypertension]. AB - Circadian rhythms in ambulatory blood pressure profiles of eight primary hypertensive patients were analyzed by nonlinear fit of a combined cosine function. Significant circadian variation in systolic blood pressure was found in each patient, and in diastolic blood pressure in seven out of eight patients. The eight primary hypertensive subjects revealed typical circadian blood-pressure profiles with two daytime maxima and a single nighttime minimum. Whereas daytime maxima differed between the subjects, all nighttime minima occurred within a narrow range of 1:54 a.m. to 4:42 a.m. The PHARMFIT-program allows to analyze in more detail the circadian blood pressure profiles obtained by ABPM in single patients as well as in a group of hypertensives. PMID- 1514305 TI - [Disordered 24-hour blood pressure rhythm in normotensive and hypertensive asthma patients]. AB - Asthmatic patients typically show a nocturnal increase in bronchial obstruction. In 100 asthmatic patients, we investigated if there is also a reduced decline of blood pressure; we used 24-h blood-pressure monitoring. The whole group consisted of 50 hypertensive asthmatic patients (group 1, 48.8 +/- 11 years, 30 females, 20 males), 25 normotensive asthmatic patients (group 2, 49.6 +/- 10 years, 22 females, 3 males) and 25 antihypertensive-treated asthmatic patients (group 3, 50.2 +/- 8 years, 15 females, 10 males). 52% of group 1, 52% of group 2, and 44% of group 3 patients showed no sufficient nocturnal systolic and diastolic blood pressure decline (less than - 15%). When we looked only for systolic blood pressure that was also the case in 82%, 92%, and 64% of the patient groups', respectively. There was no significant difference in daytime blood pressure between hypertensives (group 1) without (142 +/- 9/93 +/- 5 mmHg) and with 142 +/ 12/92 +/- 6 mmHg) sufficient nocturnal blood pressure decline, however, nighttime blood pressure (135 +/- 14/84 +/- 5 mmHg versus 123 +/- 14/72 +/- 6 mmHg) was significantly (p less than 0.0001) different. This was also true for the normotensive asthmatic patients (group 2). The results cannot be explained by differences in heart rate, degree of asthma, or in anti-obstructive medication. PMID- 1514306 TI - [Ambulatory 24-hour blood pressure monitoring of children and young adults with autosome dominant polycystic kidney degeneration]. AB - Autosomal dominant polycystic kidney disease (ADPKD) is the most frequent inherited kidney disorder leading to terminal renal failure. About 8% of the dialysis patients suffer from ADPKD, the gene frequency in the general population being about 1:1000. Many facts contribute to the hypothesis that arterial hypertension plays a major role in the pathophysiology of ADPKD. We observed a prevalence of 30% of hypertension in patients with ADPKD and normal serum creatinine, and of 80% in patients with terminal renal failure. The time of onset of abnormalities of blood pressure regulation is of great interest, since an increase of blood pressure, even in the normotensive range, accelerates the rate of progression. To answer this question, we examined the time of onset of abnormalities in blood-pressure regulation in 23 probands and 23 control patients in a cross-sectional study. The results document abnormal circadian blood pressure changes and higher blood pressures, although still within the normotensive range, in asymptomatic carriers of the ADPKD-trait, even before and more definitely after onset of puberty. Even at an age when circadian blood pressure is not significantly different, there is an increased LVM as evidence of target organ damage. The findings suggest that (intermittent) increases in blood pressure and blood-pressure-dependent target organ damage precede overt hypertension and renal failure by years or decades. PMID- 1514307 TI - [24-hour blood pressure measurement in children and adults with type I diabetes mellitus: relation to duration of diabetes, obesity, albuminuria]. AB - Early antihypertensive therapy in patients with diabetes mellitus reduces cardiovascular risk and improves long-term prognosis. Therefore, mildly hypertensive patients have to be discriminated from patients with "white coat" hypertension. 24-h-blood pressure profiles were recorded in 153 patients (age 7.9 26 years, duration of diabetes 0-21 years). The fraction of elevated blood pressure readings allows to classify these profiles independent of the age of the patient. This parameter was not related to either duration of diabetes or nocturnal excretion of albumin. In contrast, blood pressure correlated significantly with age- und sex-adjusted weight (z-score). Among 38 patients with elevated blood pressure recordings during outpatient visits, 24 (63%) displayed a normal 24-h-profile (less than 30% of blood pressure values are above the 95% limit for the respective age). These data indicate that hypertension might be independent of the metabolic derangement during the first years of diabetes. PMID- 1514308 TI - [The value of noninvasive 24-hour blood pressure measurement in patients with renoparenchymal, renovascular or severe essential hypertension]. AB - 210 patients receiving antihypertensive treatment underwent non-invasive ambulatory blood-pressure monitoring for the first time. 44 suffered from chronic renal failure, 51 had been renal transplanted, 36 had chronic glomerulonephritis, 36 had renovascular hypertension, and 43 had essential hypertension with severe end-organ damage. We analyzed the Circadian rhythm and the rate of insufficient antihypertensive treatment. While mean daytime systolic and diastolic blood pressure were not different between groups, patients with chronic renal failure, renal transplant or glomerulonephritis showed a very high rate (95-72%) of absent nighttime blood-pressure reduction. In patients with renovascular hypertension or complicated essential hypertension there was a lower rate (69-40%) of absent nighttime blood pressure reduction. The ambulatory blood-pressure monitoring led to a modification of antihypertensive treatment in 78% of patients because of nighttime hypertension. We think that ambulatory blood-pressure monitoring is an essential tool for physicians treating patients with renal disease or complicated essential hypertension. PMID- 1514309 TI - [Circadian blood pressure rhythm in hyperthyroidism and primary hyperparathyroidism]. AB - Some secondary forms of hypertension are characterized by an abnormal circadian blood-pressure rhythm. Therefore, the circadian blood-pressure variability was investigated in a prospective study using ambulatory blood-pressure monitoring in patients with hyperthyroidism and in patients with primary hyperparathyroidism. Both endocrine disorders are often associated with hypertension. Out of 17 patients with hyperthyroidism 73% were hypertensive, and out of 15 patients with hyperparathyroidism 80% were hypertensive. The blood-pressure profiles were compared to profiles from controls comprising normotensive subjects and patients with essential hypertension. The patients with hyperthyroidism and hypertension had a blunted circadian blood-pressure curve with only a small nocturnal reduction of systolic and diastolic blood pressure as compared to control patients. In patients with hyperthyroidism and normal blood pressure, the circadian blood-pressure rhythm was normal; however, in these patients the circadian heart-rate curve was blunted. All patients with hyperparathyroidism (with and without hypertension) had a normal circadian blood pressure and heart rate rhythm. From these observations we conclude that in hyperthyroidism the circadian regulation of blood pressure or heart rate is significantly blunted. The circadian blood pressure and heart-rate curve is normal in primary hyperparathyroidism. PMID- 1514310 TI - [Blood pressure variability and transient myocardial ischemia in patients with essential hypertension]. AB - To determine whether myocardial ischemia is accompanied by variation in heart rate and/or blood pressure, ST-segment analysis on Holter-ECG and ambulatory blood pressure monitoring was performed in 78 patients (64 males/14 females) with essential hypertension. Thirteen out of 55 patients (24%) with angiographically proven coronary artery disease (CAD) showed ST-segment depression (ST-D; group A pos). We observed 41 ST-D (1-11 ST-D; median: 2) lasting from 1 min to 70 min 15 s (median: 4 min 42 s) and an average depression of 185 +/- 48 mV. In comparison, in 6 of 23 patients (26%) with a normal angiogram 24 ST-D (1-10; median: 3; group B pos), which showed longer duration (1 min to 109 min 20 s; median: 11 min 10 s) and less depression (137 +/- 47 mV) have been found. 73.3% of all ST-D in group A pos and all in group B pos were preceded by an average increase in heart rate of 13 bpm. Exclusively, 12 episodes of ischemia (29.3%) in patients with CAD and 8 (33.3%) in patients without CAD were accompanied by an increase in blood pressure, which was more distinct in group A pos. Transient myocardial ischemia can be shown in hypertensive heart disease unrelated to CAD. A clear correlation between an increase in blood pressure and ST-D could not be proven. PMID- 1514311 TI - [Analysis of circadian blood pressure profiles using Fourier analysis]. AB - Blood pressure is subject to considerable circadian and situational fluctuation. In 24-h blood-pressure monitoring the severity of arterial hypertension is generally classified on the basis of the arithmetic mean of the diastolic blood pressure between 07.00 and 22.00 hours. In the present study Fourier analysis was used to generate continuous functions from the discrete blood-pressure values measured during 24-h blood-pressure monitoring in a sample of 50 normotensive persons aged from 25 to 80 years. A common reference profile was then constructed from these 50 profiles. This reference profile is characterized by the fact that the sum of the integrals over the squares of the distances between the individual profiles and the reference profile is the smallest possible. The reference profile is thus the best approximation of all normotensive profiles and practically ignores individual blood pressure fluctuations. The individual 24-h profiles of 80 patients with untreated arterial hypertension were classified on the basis of the daytime mean as mild, moderate or severe arterial hypertension and also each is described by a Fourier series. The pathological profiles were then compared with the normotensive reference profile. The comparison was made, not only with respect to the absolute pressure over 24 h, but also with respect to the circadian fluctuations in blood pressure. Comparison of the profiles shows that the Fourier analysis of 24-h blood-pressure profiles presented here permits reliable analysis and classification of arterial hypertension and can thus be used for more precise evaluation of the influence of antihypertensives on 24-h blood-pressure profiles. PMID- 1514312 TI - [Evaluation parameters of ambulatory blood pressure monitoring: mean values versus percent values]. AB - In 1039 ambulatory blood pressure (BP) recordings, we studied if mean values or blood-pressure load (% of elevated readings) is superior for evaluation. There was a nonlinear correlation between the two parameters with high correlation coefficients (syst. r = 0.98, diast. r = 0.97). At very high (low) BP levels the differentiation of the percentage-scale is insufficient, whereas in the central BP range it is too detailed as compared with the accuracy and reproducibility. Due to the nonlinear correlation with BP, treatment effects cannot be easily compared by percentage-values, since identical BP differences correspond with varying percentage. Intervals between readings are usually shorter during daytime than during nighttime. In contrast to the BP load, the resulting problems for 24 h statistics can be easily avoided by calculation of weighted mean values (from hourly means). In summary, weighted mean values are rather suited for evaluation of ambulatory blood pressure than is BP load. PMID- 1514313 TI - [PHARMFIT--a program for the evaluation of digitally collected cardiovascular parameters]. AB - The PHARMFIT program allows the non-linear fit of simple and combined cosine functions to data from long-term monitoring of cardiovascular parameters and the statistical evaluation of the quality of fit. With the SYNOPS utility a statistical comparison of different fit models can be achieved. As an example, the systolic blood-pressure data obtained in a hypertensive subject by ambulatory blood-pressure monitoring (ABPM) over a period of 36 h is used. The program demonstrates that the fit of a combined cosine function including a 24-h and a 12 h period describes the data better than a simple 24-h cosine function. The quality of fit is significantly improved by inclusion of the first harmonics. The PHARMFIT program can help to get a better analysis of ABPM data. PMID- 1514314 TI - [Analysis of long-term blood pressure measurements during sleep]. AB - Fifty patients with sleep-related breathing disorders and arterial hypertension underwent diagnostic polysomnography for two nights; EEG, EOG, EMG, and respiratory signals were recorded in parallel with invasive blood pressure. Computerized evaluation was performed to calculate systolic and diastolic blood pressure values, as well as heart rate beat-to-beat. All signals were stored once per second for further evaluation. These time series were analyzed in respect of underlying periodicities by means of spectral analysis. It was possible to distinguish four different groups of patients according to the compressed spectral arrays. Pronounced peaks of different extents were found that reflected both periodicities of respiration (3-5 s) and periodicities of sleep apnea (30-60 s). A comparison of spectral analysis of blood pressure and heart rate showed that systolic blood pressure is suited best to recognize periodicities related to respiration and apneas. PMID- 1514315 TI - [24-hour blood pressure changes in elderly people with isolated systolic hypertension, essential hypertension and normotension]. AB - In order to evaluate circadian blood-pressure (BP) profile characteristics typical of old age, we compared circadian BP profile in elderly subjects with isolated systolic hypertension (ISH; greater than 160/less than 90 mmHg), essential hypertension (EH; diastolic BP greater than or equal to 95 mmHg), and normotension (N; less than 140/less than 90 mmHg). Each group consisted of 18 subjects, approximately matched in age and sex, (age range 60-82 years; mean age 67.5 years). Ambulatory 24-h BP-monitoring was carried out using a SpaceLabs 90202 with measurements made every 30 min. In ISH, causal systolic BP is higher and circadian systolic BP is lower than in EH (n.s.). Circadian diastolic BP is lower than in EH and higher than in N; both are statistically highly significant (p less than 0.001, u-test, Wilcoxon). The decrease during the resting period is 6 mmHg in EH and 17 mmHg in ISH. In ISH there is a considerable difference of 39 mmHg between casual BP and circadian 24-h BP, in contrast to N and to EH, and this is due to a particular hyperreactivity. This discrepancy is typical of old age and holds the danger of over-treatment, if only causal BP is taken into consideration. PMID- 1514316 TI - [Ambulatory blood pressure measurement in children and adolescents with kidney transplants]. AB - Arterial hypertension (HT) is a common complication after renal transplantation. We evaluated ambulatory blood pressure profiles during 24 h in 30 pediatric patients (pts) aged 6-22 years who had been transplanted 2 months to 7 years previously. Creatinine clearance was 14-121 (median 57) ml/min/1.73 m2. Twenty three pts were being treated with ciclosporin. Sixteen pts received antihypertensive drugs. Using the monitor Nippon Collins 630 (Baxter), blood pressure (BP) values were taken every 20 min during the day and overnight (10 p.m.-7 a.m.). Five out of 10 pts with elevated office BP readings were normotensive by ambulatory blood pressure monitoring (ABPM). Ambulatory hypertension was discovered in one child with normal office BP. Echocardiography was performed in 23 pts. Five of six pts with significant left-ventricular hypertrophy (LVH), but none of the 17 pts without LVH had ambulatory HT (p less than 0.01). The physiological decline of BP during the night was significantly reduced when compared to 21 subjects of similar age with essential HT (-9.2% vs. 15.4%; p less than 0.02); no correlation was found with renal function or prednisone dose. Ciclosporin tended to reduce the day-night gradient (-14.5% vs. 9.2%; p = 0.11). One child showed a severe nocturnal BP rise of 25 mmHg. We conclude that abnormalities of nyctohemeral BP rhythm, as described in transplanted adults, can be observed to a lesser extent in children. ABPM allows a better evaluation of BP compared to office BP and, thus, may contribute to a better management of these patients. PMID- 1514317 TI - [Long-term 24-hour blood pressure measurement in genuine gestosis and hypertensive pregnancy]. AB - The clinical implications of diminished circadian blood pressure variations during hypertensive pregnancies are not fully understood. We used the COS-INOR method to quantify circadian blood pressure amplitudes of 32 patients with preeclampsia (GG) and 21 patients with superimposed pre-eclampsia (PG). The two groups did not significantly differ in body weight, age, and gestational date at admission. No differences could be detected in 24-h blood pressure values between the two groups (GG: 127 +/- 14/82 +/- 12 mmHg, PG: 128 +/- 16/86 +/- 9 mmHg). Circadian amplitudes of systolic blood pressure variations (GG: 5.9 +/- 5.5 mmHg, PG: 4.5 +/- 6.9 mmHg) and diastolic blood pressure variations (GG: 3.8 +/- 3.0 mmHg, PG: 5.3 +/- 4.1 mmHg) did not differ significantly. The slope between successive changes of mean arterial blood pressure and successive changes in heart rate was significantly higher in patients with superimposed pre-eclampsia (GG: 0.16 +/- 0.27 mmHg/bpm, PG: 0.36 +/- 0.24 mmHg/bpm, p less than 0.005). We conclude that patients with pre-eclampsia and superimposed pre-eclampsia do not differ in 24-h blood pressure and circadian blood pressure variability, however, if blood-pressure variability is related to heart-rate variability differences become apparent that might be due to altered blood-pressure regulation. PMID- 1514319 TI - [Comparison of 24-hour blood pressure measurement with ergometry in patients with hypertension]. AB - 24-h-Ambulatory blood pressure monitoring and bicycle ergometry were compared in 112 patients with untreated mild to moderate essential hypertension. Patients with high blood-pressure values above 220 mmHg during ergometry showed a significantly higher number of blood-pressure peaks above 180 mmHg. There was no significant correlation between the level of the blood-pressure rise during ergometry and the mean values of blood pressure during the 24-h period neither in the night- or the daytime period, nor of the peak values of the 24-h profile. Blood-pressure values during ergometry in patients with high numbers of systolic blood-pressure peaks above 180 mmHg during ambulatory monitoring did not differ significantly from patients with blood-pressure peaks above 180 mmHg during ambulatory monitoring. Patients with marked blood-pressure rise during ergometry seem to demonstrate a higher number of blood-pressure peaks during daytime. On the other hand, patients with an elevated number of blood-pressure peaks do not necessarily show a high blood-pressure rise during ergometry. PMID- 1514318 TI - [24-hour blood pressure measurement in type-2 diabetic patients with and without nephropathy]. AB - 24-hour ambulatory blood-pressure measurements were obtained according to criteria of the German Hypertension League in 61 non-insulin-dependent diabetic patients after admission to hospital under clinical routine conditions. 30 patients had no signs of nephropathy; 15 patients showed signs of proteinuria of more than 0.5 g/d and/or renal insufficiency, and 16 patients were on chronic hemodialysis renal replacement therapy. Despite antihypertensive therapy, the majority of NIDDM patients with nephropathy and/or dialysis therapy were hypertensive. Hypertension of non-nephropathic patients showed a better response to therapy. About 50% of all patients with nephropathy had a higher mean arterial blood pressure at night than during the daytime. In about 25% of all diabetics with nephropathy, we found, during night time, an especially pronounced increase of both systolic and diastolic blood pressure of more than 5% above the daytime values. Diabetic patients without nephropathy already show a reduced night/daytime variation of blood pressure, however, inverse circadian rhythm as a sign of prognostically non-favorable autonomic neuropathy was found almost exclusively in the nephropathic diabetic patients. PMID- 1514321 TI - [ST-segment depressions and spontaneous changes in blood pressure and heart rate in simultaneous 24-hour recording in hypertensive patients]. AB - In 15 patients with essential hypertension (but without coronary heart disease) simultaneous 24-h monitoring of the ST-segment and blood pressure was performed. Twenty-six periods with significant ST-segment depressions were recorded. In 10/26 periods with ST-segment depressions blood pressure was elevated, heart rate was increased in 20/26 ST-segment depressions. During nine periods with ST segment depressions angina pectoris was reported, and 27 anginal attacks without ST-segment depressions were observed. These data show ischemic episodes in hypertensive patients without coronary heart disease being associated with spontaneous increases of blood pressure and/or heart rate. PMID- 1514320 TI - [Diagnostic significance of absent nocturnal blood pressure decrease in 24-hour long-term blood pressure measurement]. AB - Patients (pts) with essential hypertension normally exhibit a typical diurnal variation with a nocturnal blood-pressure (BP) decreased. A lack of this periodicity is often reported in pts with secondary hypertension. 24-h BP measurement was therefore performed in 308 pts with essential hypertension, and in 172 pts with secondary hypertension, in order to evaluate the diagnostic value of nocturnal BP decrease. Diagnoses of the secondary hypertensives were: renoparenchymatous hypertension (n = 29), diabetic nephropathy (n = 24), morbus Conn (n = 6), renal artery stenosis (n = 32), pheochromocytoma (n = 5), hemodialysis pts (n = 30), and kidney transplantation (n = 44). Pts with essential hypertension showed a mean systolic and diastolic BP decrease during the nighttime period of 22 +/- 7 mmHg and 17 +/- 5 mmHg, respectively. In contrast, the corresponding values in secondary hypertension were 5.7 +/- 9.2 mmHg (systolic decrease) and 5.2 +/- 5.9 (diastolic decrease). Pts with pheochromocytoma who had a nighttime increase in BP demonstrated the greatest difference from the essential hypertensives, followed by pts with either diabetic nephropathy or after kidney transplantation. A lack of nocturnal BP decline (less than 10% of the daytime values) was detected in 69.8% of pts with secondary hypertension, but only in 5.2% of pts with essential hypertension. In summary, these results suggest that the absence of a nighttime decline in BP during 24-h ambulatory monitoring is an indication of secondary hypertension and should lead to further investigations. Furthermore, a nightly hypertension is associated with a higher risk of complications.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1514322 TI - [Wake up time, thrombocyte aggregation and the risk of acute coronary heart disease. The TRIMM (Trigger and Mechanisms of Myocardial Infarct) Study Group]. AB - A circadian variation in the incidence of acute coronary artery disease (CAD) was observed, but the correlation to possible triggering external factors and pathophysiologic mechanisms is unclear. In the "Trigger and Mechanisms of Myocardial Infarction" (TRIMM) Study, 573 patients (61 +/- 10 years; 74% male) underwent a systematic interview within 2 weeks after myocardial infarction. From 8.00 to 11.00 a.m. (peak) the relative risk of myocardial infarction was 1.9 (1.6 2.3). After statistical adjustment for individual wake-time the relative risk during the initial 3 hours after awakening was 2.7 (2.2-3.3). In 24 hour studies at platelet aggregability in 10 patients with CAD the threshold concentration of ADP (from 4.8 +/- 0.8 to 2.6 +/- 0.4 mumol, p less than 0.02) and epinephrine (from 7.3 +/- 2.3 to 1.8 +/- 0.9 mumol, p less than 0.02) decreased significantly between 6.00 and 9.00 a.m. indicating an increase of aggregability. The temporal coincidence of clinical events and physiological changes suggests a causal relationship. Further possible important factors in increasing the risk of CAD during the morning include the increase of blood pressure enhancing the risk of plaque rupture and of coronary tone at the same time of day. These results are important in determining the acute mechanisms of CAD and in improving its prevention. PMID- 1514323 TI - The peroxisomal import signal of amine oxidase from the yeast Hansenula polymorpha is not universal. PMID- 1514324 TI - Molecular cloning and analysis of autonomous replicating sequence of Candida maltosa. AB - A Candida maltosa chromosomal DNA fragment which confers high frequency transformation of C. maltosa and autonomous replication of recombinant plasmids was cloned and sequenced. Analysis of the nucleotide sequence of the cloned DNA revealed a sequence homologous for C. maltosa autonomously replicating sequence (ARS) elements. Vector pRJ1 for C. maltosa was constructed, which contained a 1.3 kb ARS sequence, pICEM-19H and the ADE1 gene of C. maltosa. Southern blot analysis suggested that the copy number of pRJ1 in C. maltosa was approximately 20 per genome. The sequence analysis also revealed an open reading frame, encoding a polypeptide with high homology (70%) to the RS15 protein of Brugia pagangi. This open reading frame has an intron with canonical sites for correct splicing in Saccharomyces cerevisiae. PMID- 1514325 TI - Efficient secretion in yeast based on fragments from K1 killer preprotoxin. AB - The alpha and beta components of the secreted K1 killer toxin of Saccharomyces cerevisiae are derived from residues 45-147 and 234-316, respectively, of the 316 residue preprotoxin (ppTox). The beta N-terminus is produced by Kex2 cleavage after Lys Arg233; when beta la (the mature sequence of beta-lactamase) is fused at this site and the fusion is expressed from the PGK promoter in pDT17, a multicopy plasmid, unexpectedly modest levels of beta la secretion resulted. Over expression of Kex2 failed to increase beta la secretion while a kex2-null mutation reduced secretion by 98%. beta la secretion in a Kex+ strain was not enhanced by inactivation of the alpha toxin component or by deletion of most of its central hydrophobic segments. However SP-beta la, produced by deletion of ppTox residues 35-176, expressed 10-fold higher beta la activity and the precursor was now secreted with similar efficiency in a kex2-null strain. Fusions of beta la to ppTox at Ala34 or Ala46 also led to efficient secretion in both KEX2 and kex2-null strains. Since these beta la fusions differ only in segments well downstream of the signal peptide and all had similar transcript levels, the efficiency of beta la secretion is apparently determined by the efficiency with which these fusions are translocated to the Golgi compartment where Kex2 is active. Efficiency is high for the shorter fusions, but is 10% or less for the longer fusions; even this fraction is apparently diverted to the vacuole if not cleaved by Kex2. SP-beta la was the most efficient construct tested; secreted beta la reached 4% of total cell protein, modestly exceeding levels produced by fusion to the MF alpha 1-encoded prepro alpha-factor, suggesting potential for the production of foreign proteins in yeast. PMID- 1514327 TI - The arginase (CAR1) gene is situated near MF alpha 1 on the right arm of chromosome XVI. PMID- 1514326 TI - Genetic and molecular analysis of DNA43 and DNA52: two new cell-cycle genes in Saccharomyces cerevisiae. AB - Two Saccharomyces cerevisiae genes previously unknown to be required for DNA synthesis have been identified by screening a collection of temperature-sensitive mutants. The effects of mutations in DNA43 and DNA52 on the rate of S phase DNA synthesis were detected by monitoring DNA synthesis in synchronous populations that were obtained by isopycnic density centrifugation. dna43-1 and dna52-1 cells undergo cell-cycle arrest at the restrictive temperature (37 degrees C), exhibiting a large-budded terminal phenotype; the nuclei of arrested cells are located at the neck of the bud and have failed to undergo DNA replication. These phenotypes suggest that DNA43 and DNA52 are required for entry into or completion of S phase. DNA43 and DNA52 were cloned by their abilities to suppress the temperature-sensitive lethal phenotypes of dna43-1 and dna52-1 cells, respectively. DNA sequence analysis suggested that DNA43 and DNA52 encode proteins of 59.6 and 80.6 kDa, respectively. Both DNA43 and DNA52 are essential for viability and genetic mapping experiments indicate that they represent previously unidentified genes: DNA43 is located on chromosome IX, 32 cM distal from his5 and DNA52 is located on chromosome IV, 0.9 cM from cdc34. PMID- 1514328 TI - A Ser/Thr-rich multicopy suppressor of a cdc24 bud emergence defect. AB - MSB2 was identified previously as a multicopy suppressor of a temperature sensitive mutation in CDC24, a gene required for polarity establishment and bud formation in Saccharomyces cerevisiae. The inferred MSB2 product contains 1306 amino acids, 42% of which are Ser or Thr. Its Ser+Thr-richness and hydrophobicity profile suggest that Msb2p may be an integral membrane protein containing a long, periplasmic, N-terminal domain and a short, cytoplasmic, C-terminal domain. Cells that lack MSB2 display no obvious mutant phenotypes. MSB2 is located between the centromere and KSS1 on the right arm of chromosome VII. Although physical mapping suggests that MSB2 and LEU1 (on the left arm of chromosome VII) are approximately 40 kb apart, the genetic map distance observed between leu1 and an msb2::URA3 marker was only 2.3 cM. PMID- 1514329 TI - Sequence of a segment of yeast chromosome XI identifies a new mitochondrial carrier, a new member of the G protein family, and a protein with the PAAKK motif of the H1 histones. AB - We have entirely sequenced an 8.3 kb segment localized on the left arm of chromosome XI of Saccharomyces cerevisiae. Five new open reading frames have been uncovered. One of them encodes a new mitochondrial carrier protein which is dispensable for growth on glycerol medium. Another could be a new member of the G protein family. A third possesses the PAAKK motif common to H1 histones. PMID- 1514330 TI - [Trypsin inhibitor activity in Basidiomycetes]. AB - 46 species of 10 families of basidiomycetes were screened for trypsin-inhibitor activity. These mushrooms were extracted with water to estimate the inhibitor activity. High inhibitor activity (trypsin inhibition higher than 50%) was estimated in 8 species of 5 families. PMID- 1514331 TI - Prophylactic laryngo-tracheal aerosolized lidocaine against postoperative sore throat. AB - A randomized, double-blind study was carried out on 193 ASA I-II surgical patients to assess the effect of aerosolized lidocaine on sore throat, hoarseness and cough in connection with tracheal intubation. The study group received aerosolized lidocaine 100 mg 2 min before tracheal intubation, using a spray. The control group received no spray. The patients underwent a standardized general anaesthesia. The patients were interviewed when leaving the recovery room and the next day in the ward. Specific questions were asked regarding sore throat, cough and hoarseness. There were no significant differences between the two groups, which suggests that topical anaesthesia of the mucosa of the upper airway is ineffective as a means of ameliorating airway complaints in connection with tracheal intubation. PMID- 1514332 TI - The effect of combined high frequency ventilation with and without continuous positive airway pressure in experimental lung injury. AB - Combined high frequency ventilation (CHFV) with 8 mmHg (1.0 kPa) continuous positive airway pressure (CPAP) and without CPAP (CHFV0) were compared to each other, and to continuous positive pressure ventilation (CPPV) with 8 mmHg (1.0 kPa) CPAP in pigs with oleic acid induced lung injury. The respiratory rate was 15 min-1 and the high frequency (HF) rate 360 min-1. Arterial carbon dioxide tension (PaCO2) was adjusted to 5 kPa and 25% oxygen was used. After CHFV, CPAP was briefly discontinued to allow the establishment of CHFV0 in order to examine the cardiovascular and pulmonary effects of combined high frequency ventilation alone. Mean arterial oxygen tension (PaO2) was 15.8 +/- 3.9 kPa during CPPV, 15.5 + 3.2 kPa during CHFV and 13.2 +/- 5.1 kPa during CHFV0 (ns). The peak airway pressure and the pericardiac pressure were lowest during CHFV0. CHFV provoked significant cardiovascular depression (mean arterial pressure, stroke index, left and right ventricle stroke work index). When compared to CPPV, a non-significant trend towards improved cardiovascular function was found during CHFV0. With similar mean airway pressures (during CHFV0) or the same CPAP (during CHFV) as during CPPV, no further improvement in oxygenation due to HF waves was found. Airway pressure was the major factor causing alterations in cardiovascular function, not the ventilation technique. PMID- 1514333 TI - Single-dose oral omeprazole for reduction of gastric residual acidity in adults for outpatient surgery. AB - Omeprazole is a substituted benzimidazole that causes dose-dependent intracellular inhibition of gastric acid secretion in humans. This double-blind study examined the effect of omeprazole in decreasing gastric acidity and gastric residual volume in outpatient adults. Unpremedicated outpatients, ASA I-III, 18 years or older (n = 17), were randomly assigned to receive omeprazole 80 mg, or placebo by mouth the night before scheduled elective outpatient surgery. The patients were fasted for 8 h prior to surgery. After the patient was anesthetized, an orogastric tube was inserted with proper placement verified by auscultation for gastric sounds. Gastric residual contents were withdrawn into a Luken's trap, and pH was then determined and gastric volume indexed to weight (ml.kg-1). Data were analyzed by a t-test, with P less than 0.05 considered statistically significant. Patient characteristics of both groups were similar. There was a statistically significant difference between the two groups for pH (P = 0.02), but not between the two groups for gastric volume indexed to weight (P = 0.07). PMID- 1514334 TI - A dose-range study of intrathecal meperidine combined with bupivacaine. AB - Twenty-one patients were included in a randomized study to receive either 10 mg of 0.5% hyperbaric bupivacaine alone or combined with 0.05, 0.1, 0.2, 0.3, 0.4 or 0.5 mg.kg-1 meperidine for spinal anaesthesia. Sensory blockade was assessed by pin prick, motor blockade by the Bromage scale, and postoperative analgesia by VAS scores and by the time before the first demand for analgesia. Spinal meperidine did not change the duration of sensory blockade, but induced a dose related increase in postoperative efficient analgesia. Spinal meperidine might be considered as a means to obtain postoperative analgesia in the hours immediately following surgery. PMID- 1514335 TI - Acupuncture treatment of severe knee osteoarthrosis. A long-term study. AB - PURPOSE: Acupuncture treatment of patients waiting for arthroplasty surgery. METHODS: 29 patients with a total of 42 osteoarthritic knees were randomized to two groups. Group A was treated while Group B served as a no-treatment control group. After 9 weeks Group B was treated too. Analgesic consumption, pain and objective measurements were registered. All objective measures were done by investigators who were "blinded" as to Group A & B. In the second part of the study 17 patients (26 knees) continued with treatments once a month. Registration of analgesic consumption, pain and objective measurements continued. Total study period 49 weeks. RESULTS: Comparing Group A to B there was a significant reduction in pain, analgesic consumption and in most objective measures. In Group A + B combined there was an 80% subjective improvement, and a significantly increased knee range movement - an increase mainly in the worst knees. Results were significantly better in those who had not been ill for a long time. In the second part of the study, it was shown that it was possible to maintain the improvements. CONCLUSIONS: Acupuncture can ease the discomfort while waiting for an operation and perhaps even serve as an alternative to surgery. Seven patients have responded so well that at present they do not want an operation. (USD 9000 saved per operation). PMID- 1514336 TI - Haemodynamic changes during spinal anaesthesia with slow continuous infusion or single dose of plain bupivacaine. AB - Forty elderly patients, scheduled for orthopaedic surgery of the hip or knee were studied. Twenty patients received a single-dose spinal anaesthesia with 3 ml of plain 0.5% bupivacaine (SDSA group). Twenty patients received continuous spinal anaesthesia using a 32- or 22-gauge catheter. A bolus of 1.0 ml of plain 0.5% bupivacaine was given to ten patients and 0.5 ml to another ten, continued by an infusion at a rate of 2 ml/h. The spread of analgesia and haemodynamic changes (central venous pressure, arterial pressures, need for sympathomimetic medication) were registered. The mean dose of bupivacaine was 2.9 ml (range 1.5-5 ml) in the CSA group (3.0 ml in the SDSA group). Eight patients in the CSA group needed medication for pain during surgery compared to five patients in the SDSA group (n.s.). The median level of pinprick analgesia at 60 min was T11 in the CSA and T6.5 in the SDSA group (P less than 0.01). The mean maximum decreases in CVP and MAP were quite similar in the CSA and SDSA group (2.1 vs 2.8 mmHg (0.3 vs 0.4 kPa) and 17 vs 21 mmHg (2.3 vs 2.8 kPa), respectively) (n.s.). Six patients in the SDSA group and four patients in the CSA group needed sympathomimetic medication. It is concluded that titration of bupivacaine for spinal anaesthesia caused only minor haemodynamic changes which were similar to those after single dose spinal bupivacaine. PMID- 1514337 TI - Recovery and discharge of patients after long propofol infusion vs isoflurane anaesthesia for ambulatory surgery. AB - Fifty unpremedicated patients scheduled for outpatient restorative dentistry and/or oral surgery lasting 2 to 4 h were anaesthetized with either propofol infusion or isoflurane inhalation. Before induction of anaesthesia with propofol (2.5 mg.kg-1), all patients were given 75 mg of diclofenac and 0.01 mg.kg-1 vecuronium intravenously. Intubation was facilitated with suxamethonium (1.5 mg.kg-1) and anaesthesia was maintained in random order either with propofol infusion (12 mg.kg-1.h-1 for the first 20 min, 9 mg.kg-1.h-1 for the next 20 min, and 6 mg.kg-1.h-1 for the rest of the anaesthesia) or with isoflurane (inspired concentration 1-2.5%), both with nitrous oxide and oxygen (30%). The patients breathed spontaneously using a non-rebreathing circuit. Patients given propofol infusion became re-orientated faster (11.0 +/- 5.5 min vs. 16.5 +/- 7.5 min; P less than 0.01) and at 30 min walked along a straight line better (P less than 0.01). At 60 min, none of the propofol patients displayed an unsteady gait, whereas 11 of the 25 isoflurane patients did (P less than 0.001). None of the patients receiving propofol had emesis at the clinic, compared with 10 of the 25 patients receiving isoflurane (P less than 0.001). The overall incidence of emesis was 2 of 25 and 14 of 25 in the propofol and isoflurane groups, respectively (P less than 0.01). Patients receiving propofol were discharged home earlier than patients receiving isoflurane (80 +/- 14 min and 102 +/- 32 min, respectively; P less than 0.01). It is concluded that propofol allows early discharge of patients, even after long anaesthesias. PMID- 1514338 TI - Continuous coeliac plexus blockade plus intermittent wound infiltration with bupivacaine following upper abdominal surgery: a double-blind randomised study. AB - In this double-blind trial, we observed the effect of intermittent wound infiltration with local anaesthetic plus continuous coeliac plexus blockade on postoperative pain relief, pulmonary function, the neuroendocrine and acute phase protein response following upper abdominal surgery. In Group A (n = 10) patients received bupivacaine intermittently into the wound and continuously into the coeliac plexus following an initial bolus. A total of 862.5 mg of bupivacaine was used over 12 h with no observed toxicity. Group B (n = 10) received equal volumes of saline. Although pain relief was poor in both groups, the bupivacaine group used less morphine postoperatively and had lower pain scores than the saline group 4 h after operation (P less than 0.05). Pulmonary function was significantly reduced in both groups with no statistical difference between the two. Significant reductions in serum glucose and cortisol were achieved (P less than 0.05), suggesting that afferent neural blockade was partially effective in attenuating the neuroendocrine response. However, the postoperative rise in interleukin-6 was not affected by this technique. It is concluded that total afferent neural blockade cannot be achieved with peripheral wound and coeliac plexus administration of relatively large doses of local anaesthetic during upper abdominal surgery. PMID- 1514339 TI - Recovery following thiopentone or propofol anaesthesia assessed by computerized coordination measurements. AB - Quantitative measurements of coordination ability and performance speed were carried out on 76 female day-case patients undergoing minor gynaecological operations. The women were assigned at random to the anaesthetic agent used, propofol 2.5 mg/kg or thiopentone 4 mg/kg. Spacing control, timing control and performance speed were recorded using a newly developed computerized coordination ability test system. The patients were tested once before the operation and 0.5, 1 and 2 h after awakening. Postoperatively the initial impairment and the subsequent regression towards preoperative test results were very similar whether the anaesthetic agent was propofol or thiopentone. Although the test apparatus was able to detect even minor differences, no postoperative test showed statistically significant differences between the two groups. We find it reasonable to conclude that there is no difference in recovery of coordination ability following propofol- or thiopentone-induced anaesthesia. PMID- 1514340 TI - Atelectasis and lung function in the postoperative period. AB - Thirteen patients with healthy hearts and lungs, and with a mean age of 68 years, who were scheduled for lower abdominal surgery during isoflurane anaesthesia with muscular paralysis, were investigated with arterial blood gases, spirometry, pulmonary x-ray and computed tomography (CT) of the chest before and during anaesthesia, as well as during the first 4 postoperative days. Before anaesthesia, lung function and gas exchange were normal in all patients. Pulmonary x-ray and CT scans of the lungs were also normal. During anaesthesia, 6 of 13 patients developed atelectasis (mean 1.0% of intrathoracic transverse area in all patients). Two hours postoperatively, 11 of 13 patients had atelectasis and the mean atelectatic area was 1.8%. Pao2 was significantly reduced by 2.1 kPa to 9.8 kPa. On the first postoperative day, the mean atelectasis was unaltered (1.8%). None of the atelectasis found on CT scanning could be detected on standard pulmonary x-ray. Forced vital capacity (FVC) and forced expired volume in 1 s (FEV1) were significantly decreased to 2/3 of preoperative level. Pao2 was significantly reduced to less than 80% of the preoperative level (mean 9.4 kPa). There were significant correlations between the atelectatic area and the impairment in FVC, FEV1, and Pao2. Spirometry and blood gases improved during the succeeding postoperative days, and atelectasis decreased. No patient suffered from pulmonary complications, as judged from clinical criteria and pulmonary x ray, in contrast to the findings of atelectasis in 85% of the patients by computed tomography. PMID- 1514341 TI - A regression model for identifying patients at high risk of hypotension, bradycardia and nausea during spinal anesthesia. AB - We analyzed the predictive value of a number of demographic and anesthesiological variables with respect to the three most common complications during spinal anesthesia: hypotension, bradycardia, and nausea. A stepwise logistic regression model was created, using data from a prospective study of 1752 patients to combine the predictive value of all entry variables. The highest risk factors for hypotension were: age greater than or equal to 50, a sensory level above Th6, receiving bupivacaine as a local anesthetic, body mass index greater than or equal to 30, and receiving opiate as a premedication. An anesthetic level above Th6 and age below 50 were primarily associated with bradycardia. Females and those with a high sensory level or receiving opiate as a premedication were at significant risk of nausea. The model was also reliably predictive for a separate group of 200 consecutive spinal anesthesia patients. Thus, the risk model may be clinically useful in identifying high-risk patients requiring additional attention. PMID- 1514342 TI - Premedication for outpatient cataract surgery: a comparative study of intramuscular alfentanil, midazolam and placebo. AB - The effects of i.m. alfentanil and midazolam on anxiety, sedation, hemodynamics, oxygen saturation and intraocular pressure were studied in 90 patients scheduled for outpatient cataract surgery with regional anesthesia. The study was randomized, double-blind, placebo-controlled, and performed on outpatients with ASA physical status I-III and mean age 67.7 +/- 11.7 years. Alfentanil (12.5 micrograms/kg) administered into the deltoid muscle had a marked anxiolytic and short sedative effect, and was associated with stable hemodynamics. Midazolam (20 micrograms/kg) administered similarly had a more prolonged anxiolytic and sedative effect, which impaired co-operation in some patients during surgery. The regional blockade was associated with a significant reduction of oxygen saturation (SpO2), regardless of the premedication used (P less than 0.05). A slight reduction of intraocular pressure (IOP) was found after premedication, but the change was not statistically significant. We conclude that i.m. alfentanil is well tolerated, and its anxiolytic and short sedative effects make it especially suitable as premedication for day-case cataract surgery. PMID- 1514343 TI - Injection pain, cardiovascular changes and recovery following induction of anaesthesia with propofol in combination with alfentanil or lignocaine in children. AB - The effect of pretreatment with alfentanil 10 (Alf10), 15 (Alf15) or 20 (Alf20) micrograms.kg-1 on reducing injection pain caused by propofol was compared with lignocaine 10 mg mixed with propofol (Lign). This double-blind, double-dummy and randomized study included 100 children with a mean age of 4.3 +/- 0.6 years, 25 children in each group, undergoing minor otolaryngological surgery. The children were premedicated orally with midazolam 0.5 mg.kg-1 and atropine 0.03 mg.kg-1. Injection pain occurred in 4% in the Lign group. The corresponding figures were 40, 16 and 20% in the Alf10, Alf15 and Alf20 groups, respectively. Both 1% lignocaine 10 mg and alfentanil 15 micrograms.kg-1 reduced injection pain significantly compared with alfentanil 10 micrograms.kg-1. Pretreatment with alfentanil significantly diminished haemodynamic responses to tracheal intubation. Furthermore, the concomitant use of alfentanil and propofol caused transient severe bradycardia and a significant decrease in heart rate after laryngoscopy. PMID- 1514344 TI - Changes in ventilatory pattern and arterial oxygen saturation during spinal anaesthesia in man. AB - Using a respiratory inductive plethysmograph and a pulse oximeter, we investigated the changes in the respiratory pattern and peripheral oxygen saturation (SpO2) of the finger before and during spinal anaesthesia in 20 surgical patients. The rib cage contribution to the tidal volume (%RC) increased significantly from before (20.4 +/- 4.3%) to during spinal anaesthesia (30.4 +/- 4.8%). However, in those patients who fell asleep 60 min after subarachnoid injection of a local anaesthetic, %RC returned to the preanaesthetic value (23.0 +/- 5.9%). Finger SpO2 increased significantly during spinal anaesthesia, but the femoral arterial oxygen saturation did not change. The authors conclude that spinal anaesthesia increases %RC in conscious patients. However, the increment of %RC does not cause a major change in arterial oxygen saturation. PMID- 1514345 TI - Heat and moisture exchangers with bacterial filters: a laboratory evaluation. AB - Six commercially available heat-moisture exchanger (HME) humidifiers with built in bacterial filtration were evaluated by laboratory tests. Physical characteristics, humidification efficiency, resistance to flow and filtration capability were investigated. The resistance was comparable for all units and did not change notably with exposure to humidity. Deadspace values were in the range 55-92 ml and weight values between 34-55 g. The humidification efficiency of two units (Group 1) was clearly less (54%-63% at 11 tidal volume), than for the other four devices (Group 2) (77%-82%). This corresponds to an average humidification output of 22.0 g/m3 for Group 1 as compared to an output of 29.9 g/m3 for Group 2. The average filtration capability of Group 1 was 99.9998%, which is somewhat higher than the 99.9973% obtained for Group 2. There are significant differences between the humidification efficiency and deadspace of different units, with the Pall Conserve device having the least satisfactory performance. All units exhibit good filtering properties, with the Pall Conserve device performing best in this respect. PMID- 1514346 TI - Serum potassium, catecholamine levels and ECG during field block for inguinal hernia surgery. AB - The purpose of this study was to find out whether hypokalaemia and associated ECG changes occur as a result of field block for hernial repair, alone or in combination with surgery. We recorded the ECG and measured the serum potassium and the plasma catecholamine concentrations at 10-min intervals in three groups of patients. In Group 1 (n = 7) and in Group 2 (n = 7), the blockade was instituted with prilocaine 0.5% and adrenaline 1:250,000, while in Group 3 plain prilocaine 0.5% was used. In Group 1 surgery was withheld for 40 min, while in Groups 2 and 3 surgery started as soon as the blockade became effective. There was a prolonged 4 to 5-fold elevation of the plasma adrenaline level from the adrenaline-containing solutions, the peak being 2.44 +/- 0.48 nmol/l (mean +/- s.d.) 10 min after the blockade had been instituted. The S-K level was unchanged in Group 1, while in Group 2 it decreased from 4.14 +/- 0.33 mmol/l to 3.91 +/- 0.29 at 60 min (P less than 0.05). An ECG pattern consistent with hypokalaemia did not develop. In Group 3, with plain prilocaine, there was a significant increase in the S-K level from 3.86 +/- 0.21 mmol/l to 4.08 +/- 0.36 at 40 min (P less than 0.05). PMID- 1514347 TI - Intramuscular low-dose ketamine versus pethidine for postoperative pain treatment after thoracic surgery. AB - In a double-blind prospective study the effects of low-dose intramuscular ketamine (1 mg/kg) were compared to pethidine (1 mg/kg) in the treatment of pain after pulmonary surgery. Thirty patients were admitted to the study and postoperatively randomized to either a ketamine or a pethidine group. The analgesic effect was evaluated using a scale ranging from 0 to 10, where 0 denoted no pain and 10 severe pain. We did not find any significant difference between the analgesic effect of ketamine and pethidine; however, the duration of action of ketamine appeared to be slightly longer. Throughout the study PaCO2 was significantly lower in the ketamine group. PaO2 increased through the study in both groups and was significantly higher after 2 h. Heart rates increased significantly only in the pethidine group. Mean arterial pressures remained unchanged and the respiratory frequencies were similar in the two groups. The incidence of adverse reactions was low and not significantly different between the groups. The findings indicate that low-dose intramuscular ketamine is a potent analgesic for postoperative analgesia following thoracic surgery and that it has no respiratory depressive effect. PMID- 1514348 TI - Alfentanil inhibits muscle fasciculations caused by suxamethonium in children and in young adults. AB - The effect of alfentanil on suxamethonium-induced muscle fasciculations was studied in a double-blind study in 34 children (mean age 6.8 years) and in 30 adults (mean age 20 years). After pretreatment with either alfentanil 50 micrograms kg-1 or saline, each patient was anaesthetized with a sleep dose of thiopental followed by suxamethonium 1.5 mg kg-1 for endotracheal intubation. Compared to the control groups, alfentanil significantly decreased the intensity of visible muscle fasciculations caused by suxamethonium. In children, the duration of muscle fasciculations was shorter in the alfentanil than in the control group. In adults, the intensity rather than the duration of fasciculations was attenuated by alfentanil. The inhibition of fasciculations caused by alfentanil was also demonstrated in children in the surface electromyogram recorded on the biceps. There was no circulatory response to endotracheal intubation in the groups pretreated with alfentanil. PMID- 1514349 TI - Oxygen consumption after flumazenil reversal. AB - The effect of flumazenil reversal of midazolam-induced anesthesia on whole body oxygen uptake (VO2) was investigated in a double-blind trial in 48 patients (ASA, 1 or 2) undergoing elective surgery under general anesthesia. VO2 was measured in spontaneously breathing patients during recovery from anaesthesia induced with midazolam 0.25 mg.kg-1 and maintained with nitrous oxide 60% in oxygen and halothane. The level of sedation was evaluated by a subjective score. To reverse midazolam-induced anesthesia, patients were randomly allocated to receive placebo or flumazenil (6 micrograms.kg-1). No significant changes in VO2 (160 +/- 53 vs 150 +/- 39 ml.min-1.m-2 or sedation score (2.5 +/- 1.0 vs 2.1 +/- 0.9) were observed in the placebo group. After flumazenil administration, the sedation score significantly (P less than 0.05) improved (2.9 +/- 1.0 vs 1.3 +/- 0.8) whereas no significant change in VO2 was observed (158 +/- 67 vs 157 +/- 61 ml O2.min-1.m-2). These data show that reversal of benzodiazepine effects with flumazenil resulted in no significant change in oxygen uptake. PMID- 1514350 TI - Adenosine infusion during isoflurane-nitrous oxide anaesthesia: indications of perioperative analgesic effect. AB - Adenosine, an endogenous compound with a known antinociceptive effect when administered into the CNS, was applied in nine patients (21-65 years) by the peripheral intravenous route (70-130 micrograms.kg-1.min-1) as a replacement for peroperative opioids during inhalation anaesthesia for surgical procedures not requiring muscle relaxation. Lorazepam was given as premedication, thiopentone was used for induction, and succinylcholine facilitated intubation of the trachea. Anaesthesia was maintained with isoflurane [initial surgery endtidal concentration (ET) 0.88% (range 0.7-1%)] and nitrous oxide (60-70%) in oxygen. Adenosine infusion was initiated 5-10 min prior to surgery, and stopped close to or when isoflurane was terminated at the end of surgery. The duration of anaesthesia, adenosine infusion, and surgery were 120 min (range 80-165), 90 min (range 70-145), and 90 min (range 60-135), respectively. Spontaneous unassisted ventilation was maintained in all patients. Mean heart rate increased 10 beats.min-1 (range 0-35) upon induction of surgery, while systolic blood pressure was unaffected at 105 mmHg (range 85-120) (14 kPa (range 11.3-16.0)). Spo2 and ETCO2 were in the normal range. The isoflurane concentration was gradually reduced in most cases [mid-surgery ET 0.63% (range 0.5-0.8) and end-surgery ET 0.57% (range 0.3-0.8)]. Extubation and verbal communication were rapidly achieved after anaesthesia. The mean postoperative (24 h) opioid requirement was 4 mg (range 0-10 mg). These pilot cases suggest that systemic adenosine infusion may replace opioids during inhalation anaesthesia, and that adequate spontaneous ventilation can be achieved. PMID- 1514351 TI - Vascular effects of propofol during cardiopulmonary bypass. PMID- 1514352 TI - Two types of atrioventricular dissociation. PMID- 1514353 TI - Morphometric and stereological study of the seminal vesicle of the guinea pig. AB - The seminal vesicle of the guinea pig has been widely used as a model for the study of hormonal action on the male accessory sex organ, but there have been few attempts to quantify their cellular and tissue components. In the present study, the seminal vesicle of the guinea pig was described in the form of a morphometric model. Tissue samples were taken from the distal, middle and proximal regions of the gland and processed for light microscopy. Using a combination of a stereological point-counting technique and direct measurement, the relative volumes of different components (lumen, epithelium, lamina propria and fibromuscular layer) were determined. The relative numbers of the secretory cells and basal cells were also estimated. Following the estimation of the average size of the seminal vesicle, the relative volume of different components and the relative number of secretory cells were transformed into absolute data on a per average seminal vesicle basis. Similarly, the average sizes of the secretory cells and nuclei were also determined. The quantitative data generated from the present study will serve as a baseline for further studies of the seminal vesicle of the guinea pig. The techniques used in the present study are easy to apply, and data generated were objective and reproducible. PMID- 1514354 TI - Nonresponsiveness of the thyroid gland to goitrogen in the early neonatal period in the rat: light- and electron-microscopic observations. AB - The thyroid response of fetal and neonatal rats to propylthiouracil (PTU) as a goitrogen was studied with observation of the thyroid glands by light and electron microscopy. On day 19 of gestation and on days 1, 3, 5 and 8 after birth, fetal and neonatal rats were given a subcutaneous injection of PTU and were autopsied 2 days later. PTU induced conspicuous goiters in fetal rats but did not in neonatal rats aged up to day 5 after birth. Beyond that age, PTU again induced goiters. Histologically, the follicular cell height in goitrous thyroid glands was significantly increased. Ultrastructurally, follicular cells in goitrous thyroid glands often had colloid droplets and lysosomes. It seems that nonresponsiveness of the thyroid glands in early neonatal rats to goitrogen is due to a temporary decline of the pituitary activity of thyrotropin secretion. About 5 days or more after birth, the pituitary-thyroid system begins to operate again in response to goitrogen. PMID- 1514355 TI - Morphometric variations of the lumbar vertebrae between Chinese and Indian adults. AB - A morphometric study of the lumbar vertebrae of 126 adult skeletons, 90 Chinese and 36 Indian, of both sexes without marginal osteophytes were performed. In each lumbar vertebra, the cephalad and caudad midsagittal diameters, the interpedicular diameter of the spinal canal as well as the midsagittal and transverse diameters and the height of the vertebral body were measured. The results showed that the midsagittal and transverse diameters, the heights of the lumbar vertebral bodies and the interpedicular diameters of the lumbar spinal canals increased progressively from L1 to L5, while the midsagittal diameters of the lumbar spinal canals decreased progressively from L1 to L5 in both Chinese and Indian adult skeletons. The lowest mean values of the cephalad and caudad midsagittal and the interpedicular diameters of the spinal canals in Chinese were found to be 5.04 +/- 0.15 mm at L5, 4.67 +/- 0.09 mm at L5 and 25.92 +/- 0.20 mm at L2, respectively, while in Indians they were found to be 4.54 +/- 0.18 mm at L5, 4.25 +/- 0.10 mm at L5 and 25.42 +/- 0.22 mm at L1, respectively. In addition, the mean diameters of the spinal canal and the vertebral body (except the height of the vertebral body) were significantly greater in the Chinese than in the Indian skeletons. The above findings indicate that the mean diameters of both the lumbar spinal canal and the vertebral body vary greatly between Chinese and Indian adults, i.e. there are no mean values of the vertebral dimensions that are valid for all populations.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1514356 TI - [Biomechanics of the joints of the large toe. Shape and movement of the first tarsometatarsal joint and of the medial cuneonavicular joint]. AB - 90% of the first (hallucal) tarsometatarsal joints are screw-shaped; the axis is directed upwards to the front touching the lateral edge of the joint. Thus the plantar flexion is inevitably accompanied by an adduction and a pronation, and vice versa a dorsiflexion is consequently accompanied by an abduction and a supination, when the articular surfaces exactly slide along each other. 10% of these joints, however, are ellipsoid-shaped; in this case the distal articular surface of the medial cuneiform bone has the form of an ovoid head, and a strong ligament situated next to the lateral edge of the joint effects the same kind of motion described above. The medial cuneonavicular joint is always ellipsoid shaped, the head of which is made up by the medial facet of the distal articular surface of the navicular bone. Each of the two joints mentioned has a considerable range of mobility. PMID- 1514357 TI - Tight junctions of human uterine epithelial cells change during the menstrual cycle: a morphometric study. AB - Tight junctions between luminal epithelial cells of the human uterus were studied by freeze-fracture electron microscopy. It was found that junctional complexity decreased during the menstrual cycle, and we explore how this finding may contribute to the role of the uterus in facilitating implantation. PMID- 1514358 TI - Light-microscopic demonstration of methylene blue accumulation sites in mouse brain after supravital staining. AB - Mouse brains were stained supravitally with methylene blue and studied in paraffin sections by light microscopy. In the perikarya, the dye was found to bind primarily to the nuclei; only slight staining of the cytoplasm was observed. Dye accumulations within nerve fibers were found in the nodes of Ranvier and in the varicosities of the unmyelinated endings. Specific dye binding in dendrites corresponded mainly to beads and spines. The accumulation sites in terminal neuronal processes appeared to be closely related to the plasma membrane. These morphological data would explain the neurophysiologically proven interaction of the dye with calcium-binding sites in membranes. PMID- 1514359 TI - Liver development in rats during the embryonic period (Carnegie stages 11-14). AB - The hepatic structures appearing during Carnegie stages 11-14 were analyzed in a series of 61 OFA rat embryos. The group of embryos (crown-rump length 2-7 mm, 10th-12th days after coitus) was composed of 52 specimens of the somite period (stages 11 and 12) and of 9 specimens of the postsomite period (stages 13 and 14). The embryos were submitted to serial histological sectioning with graphic reconstruction. Stage 11 was characterized by the development of the hepatic diverticulum induced by differential growth of the endodermal plate and fixed contact between the entoderm and endothelium lining the heart. Stage 12 presented obvious signs of cellular differentiation, the septum transversum giving the liver stroma and the hepatic diverticulum the epithelial trabecula. At stage 13 the epithelial cords enmeshed the stromal capillaries, while hepatocardiac veins drained the hepatic flow into the sinus venosus. Stage 14 was recognized by the presence and development of the hepatic lobes and the enlargement of vascular channels. The cystic bud was never observed. The identification of these features permits to precise the hepatic developmental staging in rats and to obtain accurate criteria for the characterization of the end of the somite period and the beginning of the postsomite period. PMID- 1514360 TI - Long-term effects of alloxan-induced diabetes on the nucleus ventralis posterolateralis in the thalamus of the rat. AB - The present paper describes the long-term ultrastructural changes in the nucleus ventralis posterolateralis of the thalamus of male Wistar rats after alloxan induced diabetes. Degenerating dendrites were characterized by an electron-dense cytoplasm with scattered endoplasmic reticulum and ribosomes. Degenerating axon terminals were characterized by an electron-dense cytoplasm and clustering of small spherical agranular vesicles. Degenerating axon terminals formed axosomatic synapses with seemingly normal cell bodies and axodendritic synapses with normal as well as degenerating dendrites. Degenerating axons (both myelinated and unmyelinated) were readily encountered in the neuropil. Activated microglial and astrocytic cells in the neuropil were in the process of phagocytosis or had residua in their cytoplasm. PMID- 1514361 TI - A comparison of the immunohistochemical localization of type I and type II collagens in craniofacial cartilages of the rat. AB - The immunohistochemical localization of types I and II collagen was examined in the following 4 cartilaginous tissues of the rat craniofacial region: the nasal septal cartilage and the spheno-occipital synchondrosis (primary cartilages), and the mandibular condylar cartilage and the cartilage at the intermaxillary suture (secondary cartilages). In both primary cartilages, type II collagen was present in the extracellular matrix (ECM) of the whole cartilaginous area, but type I collagen was completely absent from the ECM. In the secondary cartilages, type I collagen was present throughout the cartilaginous cell layers, and type II collagen was restricted to the ECM of the mature and hypertrophic cell layers. These observations indicate differences in the ECM components between primary and secondary craniofacial cartilages, and that these differences may contribute to their modes of chondrogenesis. PMID- 1514362 TI - [The posterior intervertebral spaces of the craniovertebral joint]. AB - Closing of the posterior intervertebral spaces of the craniovertebral joint is not performed by the classical posterior atlanto-occipital and atlantoaxial membranes. In the atlanto-occipital space, the connective laminae come from the occipital periosteum and from the anterior fascia of the rectus capitis posterior minor muscle, and pass round the anterior side of the posterior arch of the atlas to reach the spinal dura mater. In the atlantoaxial space, the anterior fasciae of the rectus capitis posterior major muscle and of the inferior oblique muscle, as well as the periosteum of the posterior arch of the atlas, extend to reach the spinal dura mater. Thus, the epidural space is sealed posteriorly by the connective laminae of the atlantoaxial space, and lets above a superior recessus containing the ganglia of the spinal nerves C1 and C2 and in which the vertebral artery transits. PMID- 1514363 TI - The pretectal complex of the rabbit: distribution of acetylcholinesterase and reduced nicotinamide adenine dinucleotide diaphorase activities. AB - The chemoarchitecture of the pretectal complex of the rabbit was examined in sections stained by acetylcholinesterase (AChE) and reduced nicotinamide adenine dinucleotide (NADH) diaphorase in the coronal, horizontal and sagittal plane. Twelve different subdivisions can be identified in the rabbit pretectum on the basis of the distribution of both histochemical markers. According to the standard terminology, the pretectal complex of the rabbit consists of: the nucleus of the optic tract; the anterior, posterior, olivary and medial pretectal nuclei; the nucleus of the posterior commissure; the periventricular subcommissural gray; the suprageniculate and internal suprageniculate nuclei, and the dorsal, lateral and medial terminal nuclei of the accessory optic system. The combined use of several sectioning planes and the histochemical mapping of AChE and NADH diaphorase have been of value in resolving the structural limits within transitional regions of the pretectum. PMID- 1514364 TI - Elbow extensor muscles of the horse: postural and dynamic implications. AB - Based on histochemical and immunohistochemical evidence, horse elbow extensor muscles are composed of two morphologically distinct muscle groups. The long and lateral heads of the triceps brachii are large, predominantly type II (presumed fast) muscles. The long and lateral heads of the triceps together account for 96% of the weight of the elbow extensors (long head of triceps is 81%). The long and lateral heads contain three histochemical fiber types: types I, IIa and IIb. Type I muscle fibers account for approximately 18 and 27% of the fibers in the long and lateral heads of the triceps, respectively. In the lateral head, type IIa and IIb fibers account equally for the remaining 70%, while in the long head of the triceps type IIb fibers predominate (50%) over type IIa fibers (32%). In contrast, the much smaller medial head of the triceps (2% of triceps mass) and the anconeus (2% of mass) contain almost exclusively type I muscle fibers. It is hypothesized that the medial head and anconeus, with their slow fibers, contribute to the postural maintenance of the forelimb by preventing flexion at the elbow joint during passive stance. The larger long and lateral heads, with their generally fast fiber populations, are most likely important during dynamic activity. PMID- 1514365 TI - Distribution of oxytocin and vasopressin neurons in the diencephalon of the Japanese horseshoe bat, Rhinolophus ferrumequinum. An immunohistochemical study. AB - The distribution of oxytocin (OXT) and vasopressin (VP) neurons in the diencephalon of the hibernating Japanese horseshoe bat, Rhinolophus ferrumequinum, was immunohistochemically investigated by the avidin-biotin complex method. Magnocellular OXT and VP neurons were localized mainly in the paraventricular nucleus and the supraoptic nucleus. In addition to these main nuclei, both kinds of magnocellular neurons were also found in the periventricular nucleus, perifornical area and lateral hypothalamic area. Extensively distributed parvocellular neurons containing only VP were observed in the rostral and middle portions of the suprachiasmatic nucleus. The size of OXT and VP magnocellular neurons was almost equal in the paraventricular and ventromedial supraoptic nuclei, whereas VP neurons were significantly larger than OXT neurons in the dorsolateral supraoptic nucleus. The OXT and VP cells in the ventral supraoptic nucleus showed a distinctive elliptical shape. Both OXT and VP fibers were distributed in the lateral habenular nucleus, stria medullaris thalami, lateral preoptic area, stria terminalis, and medial and supracapsular part of the bed nucleus of the stria terminalis. Moreover, OXT fibers were found in the substantia nigra, and VP fibers were noted in the nucleus reunions and the paraventricular nucleus of the thalamus. PMID- 1514366 TI - Failure to detect a second-generation effect in female mice after neonatal treatment with an estrogen (diethylstilbestrol). AB - Inbred female mice of the NMRI strain were treated subcutaneously with 5 micrograms diethylstilbestrol (DES) in olive oil or vehicle only for the first 5 days after birth. One group of DES-treated females was killed at the age of 8-12 weeks, and the uterine cervix and adjacent parts of the vagina and uterine horns prepared for histological studies. In all preparations, the cervical epithelial lining contained regions with heterotopic columnar epithelium (HCE) along 69-100% of the length of the common cervical canal. Ovaries from neonatally DES-treated females were grafted to 8-week-old ovariectomized control hosts and these hosts were mated to control males 2 weeks later. The hosts gave birth to normal-sized litters. The female offspring from these litters had a normal cervical epithelial lining and, in turn, gave birth to normal-sized litters. These results indicate that treatment of neonatal female mice with DES does not affect the female germ cells as far as concerns factors associated with the development of HCE or reduced fertility in the next generation. PMID- 1514367 TI - The suprascapular nerve as re-interpreted by its communication with the phrenic nerve. AB - A particular nerve bundle which may be called phrenicosuprascapular communication is, although only rarely, met with in various forms in man. By teasing, fibres of this communication are revealed to belong to the most anterior components of the brachial plexus, being closely associated with anterior nerves such as the phrenic, accessory phrenic, subclavius and even pectoralis. It is, therefore, obvious that the nervus suprascapularis conveys anterior fibres. It may be interpreted that the anteriormost nerve fibres may be separated from the main cord(s) and form an irregular network or plexus for themselves. It should be stressed that the n. suprascapularis consists of all the anterior components of the brachial plexus and that this is an anterior nerve. PMID- 1514368 TI - Effects of alcohol and caffeine on cultured whole rat embryos. AB - The direct effects of ethanol and caffeine on embryogenesis were investigated using the whole rat embryo culture system. Compared to control embryos, the crown rump length, number of somites, branchial bars, and morphological score were significantly reduced in embryos exposed to ethanol, caffeine, or both substances. Development of the craniofacial region, cardiac primordium and forelimb was delayed following ethanol treatment. Compared to the controls, the anterior neuropore lagged in development following caffeine treatment; closure of the posterior neuropore was significantly delayed in each of the treatment groups. The optic and olfactory primordia were not affected. The results indicate that alcohol and caffeine independently affect the embryo, but when combined their effects were not potentiated. PMID- 1514371 TI - [The pedicled transposition of the digastric and stylohyoid muscles in the treatment of velopharyngeal incompetence. Anatomic basis and clinical application]. AB - The anatomical basis for the application of neurovascular pedicled muscle transfers of the digastric and stylohyoid muscles in the treatment of velopharynx incompetence is described. The fact that the neurovascular pedicle is located in the cranial third of the muscle bellies provides the safety of the operative procedure. The muscles have to be dissected with respect to that. The direction in which the transferred muscles pull is described. The muscle transposition is combined with the classic Wardill-Kilner operation to lengthen the soft palate. The transferred muscles have to avoid scar contraction and shortening of the soft palate and to gain a muscular function of the soft palate. The clinical use is justified in rare cases as demonstrated in one case. PMID- 1514369 TI - [Nasal cavities and paranasal sinuses in newborns and children]. AB - The paranasal or accessory nasal sinuses begin their development as evaginations of the mucosa during the 3rd and 4th fetal months, but undergo their major expansion after birth according to the development of the facial cranium and the teeth. While in the newborn the sphenoidal and frontal sinuses are still only predispositioned, the ethmoidal labyrinth and particularly the maxillary sinus are of appreciable size. In the 4-year-old the frontal and sphenoidal sinuses are already developed and in the 12-year-old the paranasal sinuses reach their final form and a size equivalent to the adult. PMID- 1514370 TI - Relationship between morphological signs of cell injury in myocardial ischaemia. AB - Morphological signs of severe ischaemic injury are well known. However, we still lack knowledge about how indices of milder injuries are related on a cellular level. In a previous study we have reported on the sequence of alterations across the border zone in cat hearts subjected to 3 h of coronary occlusion. In the present study, which elaborates that study, we have examined the relationship between morphological variables in serial sections of 220 myocytes within the border zone. In cells with intact sarcolemma and no chromatin changes, the fractional volume of cytoplasm has a bimodal distribution indicating cells with and without oedema. Whereas cells with focal disruptions of the sarcolemma have a moderate oedema, usually localized submembranously, cells with extensive sarcolemmal fragmentation have an extensive oedema. A mild oedema is seen before other signs of severe cell injury, even though more extensive oedema is closely associated with sarcolemmal fragmentation. The fractional volume of mitochondria was smaller, whereas the fractional volume of lipid droplets was larger in cells with oedema than in cells without oedema. PMID- 1514372 TI - Morphological study of fetal nasopharyngeal epithelium in man. AB - In 30 human fetuses between 8 and 13 weeks of intrauterine life the lateral wall of the nasopharynx was examined by light microscopy and transmission and scanning electron microscopy. In the subjects between 8 and 9 weeks in utero the mucosa displays still an immature appearance, being mono- or bistratified and lacking the characteristic structures of the respiratory epithelium. Nevertheless, signs of differentiation are to be noticed, with the presence of two distinct cellular types that, in the later periods, will give rise to ciliated cells and microvillus-provided cells. An almost complete differentiation will be reached at 12-13 weeks in utero, even if goblet cells are still lacking in the examined zone during the considered period. Nonrespiratory types of epithelium, such as transitional or squamous, were never found in the studied subjects. PMID- 1514373 TI - Postnatal development of the dentate gyrus: a karyometric and topographic study. AB - We have analysed the postnatal development of the nuclear sizes of the granular cells of the dentate gyrus in 5- to 190-day-old male mice. The study was performed in three topographic levels: rostral, intermediate and caudal. Three subdivisions were analysed in each level: suprapyramidal blade, infrapyramidal blade and the transition between them, the angular zone. Additionally, each of these subdivisions was measured in its external and internal layer, separately. Three gradients of postnatal karyometric development can be described: external to-internal, suprapyramidal-to-infrapyramidal, and caudal-to-rostral, indicating that the external, suprapyramidal and caudal cells show higher karyometric sizes than the other subdivisions. These gradients are related to the ontogenetic gradients of these neurons. PMID- 1514374 TI - Differential localization of G proteins, Gi and Go, in the olfactory epithelium and the main olfactory bulb of the rat. AB - The immunohistochemical localization of proteins Gi1 (plus Gi3). Gi2 and Go was studied in the olfactory epithelium and the main olfactory bulb of rats, using purified antibodies to the respective alpha subunits and beta gamma subunits of these G proteins. In the olfactory epithelium, only a restricted population of olfactory cells was immunopositive for Gi2 alpha, but others were not. The immunoreactivity for Gi1 alpha/Gi3 alpha was not observed. The olfactory epithelium was immunopositive for both Go alpha and beta gamma, but its apical surface was immunopositive only for beta gamma. In the main olfactory bulb, all layers were intensely immunopositive for Go alpha and beta gamma but weakly for Gi2 alpha. In contrast to the negative or weak immunostainings in the olfactory nerve fiber layer and glomeruli, the molecular and the internal granular layers were intensely immunopositive for Gi1 alpha/Gi3 alpha. These findings suggest the functional difference among Gi1/Gi3, Gi2 and Go in the signal transduction in the olfactory system. PMID- 1514375 TI - Studies on the microvascularization of the digestive tract by scanning electron microscopy of vascular corrosion casts. 2. Bile duct in guinea pigs. AB - The microvascularization of the bile duct was studied in 20 adult guinea pigs (Cavia porcellus) using microvascular corrosion casts in the scanning electron microscope. The main supplying and draining vessels are located in the adventitial layer; from there they form the subepithelial capillary network. The microangioarchitecture of the common bile duct is reminiscent of that of the cystic and hepatic ducts. The diameter of these ducts is 1,000 microns on average. The microvascular arrangement in the bile duct suggests a probable involvement of the capillaries in the absorption of bile hormones. PMID- 1514376 TI - Computer 3-dimensional reconstruction of intraglandular lymph vessels and ductal systems of the human submandibular gland. AB - Computer three-dimensional reconstruction of serial sections is currently an active area of research. In this paper we combine computer graphics, image processing and biomedical techniques to reconstruct a stereo model of intraglandular lymphatic vessels, veins, arteries and ducts from serial microsections of the human submandibular gland. PMID- 1514377 TI - Electron-microscopic localization of baboon acrosomal antigens using antisperm monoclonal antibody. AB - A sperm antigen corresponding to baboon sperm monoclonal antibody 1A9 was localized in the testis and ejaculated sperm in this animal, using the immunofluorescence technique and immunogold labelling. Immunohistochemical studies of the baboon testis showed that the antigenic determinant was localized in the late spermatid cells and spermatozoa close to the seminiferous tubules. Immunofluorescence studies indicate that the protein was localized on the acrosome region of ejaculated baboon sperm. At the electron-microscopic level, gold particles indicative of the presence of this determinant recognized by 1A9 monoclonal antibody were detected on the inner acrosomal region of ejaculated baboon sperm. PMID- 1514378 TI - Stereological studies of the parathyroid gland of phosphate-treated golden hamsters subjected to a hypergravity environment. AB - The ultrastructure of the parathyroid glands of phosphate-treated golden hamsters exposed to a 5-G environment was studied. In the phosphate-treated animals exposed to a hypergravity environment, the Golgi complexes associated with numerous prosecretory granules, and the enlarged intercellular spaces containing floccular or finely particulate material showed a significant increase compared to those of the control, centrifuged, and phosphate-treated groups, and the cisternae of the granular endoplasmic reticulum showed a significant increase compared to those of the control and phosphate-treated groups. In addition, numerous secretory granules were situated close to the plasma membrane of chief cells in the phosphate-treated animals exposed to a hypergravity environment. These findings suggest that the synthesis, and to a greater extent the release of secretory granules may be markedly stimulated, in the parathyroid glands of phosphate-treated animals exposed to a hypergravity environment. PMID- 1514379 TI - Evidence of the occurrence of calcitonin cells in the ultimobranchial follicle of the rat postnatal thyroid. AB - A study on thyroid glands of Wistar rats of ages ranging from 1 to 120 days was carried out. The glands were serially sectioned and stained for calcitonin using the peroxidase antiperoxidase method. All the thyroids contained ultimobranchial follicles (UBF) located partially embedded among the usual follicles but in a 5 day-old rat this structure showed an unusual position in the interstitium of connective tissue between the cartilage of the trachea and the thyroid gland. We have observed in the wall of that UBF the presence not only of resting C cells but also mitotic figures of C cells. Furthermore, on the opposite side of the same UBF an active area of formation of thyroid follicles was found. These observations provided the first evidence of the contribution of the UBF in the formation of C cells during the postnatal life of the rat. Furthermore, it is suggested that some C cells may share a common origin with ultimobranchially derived follicular cells. PMID- 1514380 TI - Functional construction of the sacroiliac ligamentous apparatus. AB - The sacroiliac ligamentous apparatus was examined as a part of a biomechanical pelvis-lower extremities system. The ligamentous apparatus of two pelves was freed, and the findings concerning the ligaments and their direction were drawn by a modular constructed, three-dimensional calculator model of the pelvic region. The ligamentous apparatus of the sacroiliac joint belongs to a functional system. Its task is to minimize every movement in this amphiarthrosis. The ligamentous apparatus shows an adaptation to strong or long-time-acting stresses. The junction between the os sacrum, pelvis and the ligamentous apparatus of the sacroiliac joint can be described as self-tightening. Local stresses are also reduced by the ligaments. A loosening in this system, which has to fix the os sacrum to the pelvic girdle, leads to a static insufficiency. The consequence is pain due to an irritation of the lumbosacral trunk. The exact description of the structure allows a representation according to the laws of similarity mechanics. With such a representation one can build up a computer-aided biomechanical model of the pelvis-lower extremities region. Examples for such a model are biomechanical finite-element models. By observing the laws of similarity mechanics (an exact description of geometric, physical and functional conditions) an efficient biomechanical model can be constructed that also takes into consideration the complex functional circumstances, in contrast to previous models. In order to construct such a model, one has to feed the findings of the examination into a data bank, which has to be demanded. PMID- 1514381 TI - Connections between the supratemporal and its rostral areas, and the posterior thalamic region in the monkey: a retrograde HRP study. AB - Connections between the anterior half of the superior temporal gyrus (Ts) and the supratemporal plane (STP) in the Sylvian fissure, and the posterior thalamic region in the monkey were studied after retrograde transport of horseradish peroxidase (HRP). HRP injections into the Ts resulted in labeled cells in the posterodorsal division of the principal medial geniculate complex (GMpd), the suprageniculate and limitans nuclei, and the medial part of the medial nucleus of the pulvinar complex. HRP injections into the rostral Ts led to labeling in the posterior extremity of the GMpd, whereas injections into the caudal Ts resulted in labeling in the rostral GMpd. HRP injections into the area of transition between the Ts and STP led to labeling in the ventral part of the ventral division of the principal medial geniculate complex (GMv) and in the GMpd. HRP injections into the rostral STP led to labeling in the lateral part of the GMv, the anterodorsal division of the principal medial geniculate complex (GMad), and the lateral division of the posterior nucleus (Pol). HRP injections into the more caudal part of the STP yielded labeling in the more dorsomedial part of the GMv, Pol, and GMad. HRP injections into the lip of the STP yielded labeling in the GMv, Pol, GMad, and GMpd. PMID- 1514382 TI - [An aberrant muscular nerve to the latissimus dorsi muscle from the posterior cutaneous nerve of the arm]. AB - In the 1987 student course on gross anatomy dissection of cadavers at Iwate Medical University School of Medicine, an aberrant muscular nerve to the latissimus dorsi muscle arising from the posterior cutaneous nerve of the arm was found bilaterally in a 65-year-old female who had died of acute pneumonia. The case was investigated anatomically. The posterior cutaneous nerve of the arm arose from the radial nerve approximately at the lateral axial border as the first branch independently on the right, and by forming a trunk with the nerve to the long head of the triceps brachii muscle on the left. The aberrant muscular nerve originated from the posterior cutaneous nerve of the arm about 3 cm distally to the point of the branching of the cutaneous nerve from the radial nerve. This aberrant nerve entered the latissimus dorsi muscle near the transitional area from the muscular part to the tendinous part while dividing into three on the right, and without dividing on the left. The side into which the aberrant nerve entered was just the reverse of the side into which the thoracodorsal nerve and artery supplied. The muscular part innervated by the aberrant nerve was bounded by a tendinous intersection for the most part of the latissimus dorsi muscle innervated by the thoracodorsal nerve. The intramuscular nerve distribution of the aberrant nerve was investigated under a binocular dissecting microscope. It was revealed that there was no communication between the ramification of the aberrant nerve and that of the thoracodorsal nerve.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1514383 TI - [A case of the right aortic arch with the left subclavian artery as its last branch]. AB - A case of the right aortic arch with the left subclavian artery as its last branch was found in an 80-year-old Japanese female cadaver during the 1990 dissection for students. The main findings were as follows. The ascending aorta arose from the left ventricle and ran right and upward to the level of the intervertebral disc between the 2nd and 3rd thoracic vertebrae. It then curved right and backward to form the aortic arch. The aortic arch joined the thoracic aorta that descended along the right side of the vertebral column and crossed obliquely the vertebral column at the level of the 8th thoracic vertebra. Finally it entered the abdomen through the aortic hiatus behind the esophagus. Four branches were given off from the aortic arch in the following order from left to right: the left common carotid, the right common carotid, and the right subclavian and the left subclavian arteries. The left subclavian artery, which had an aortic diverticulum at the origin of the aortic arch, ran left and upward behind the esophagus. The ligamentum arteriosum connected the left pulmonary artery with the aortic diverticulum of the left subclavian artery. The left common carotid artery, which normally had no branches before entering the cranium, gave off an accessory esophageal branch about 20 mm distally from its origin. The right and left vertebral arteries entered the transverse foramen of the 6th cervical vertebra. The left recurrent laryngeal nerve hooked around from the left dorsal to the right ventral part of the ligamentum arteriosum.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1514384 TI - Appearance of monocytes and macrophages in the embryonic thymus of the mouse: light and electron microscopic studies. AB - Development of the embryonic thymus was studied by light and electron microscopy, particularly with reference to the appearance of macrophages. The thymus anlage appeared at 12 days of gestation. Then, at 14 days, the anlage was invaginated by mesenchymal septa carrying small blood vessels. In the embryonic thymus, macrophages and monocytes were present as early as 15 days of gestation. Monocytes as well as macrophages laden with phagocytic inclusions first appeared in the perivascular space or very close to blood vessels at the cortico-medullary junction. The perivascular space was continuous with the mesenchyme surrounding the thymus. From 15 to 17 days, monocytes could often be seen in the perivascular space. The origin of thymus macrophages was discussed in relation to a route for movement of macrophage precursors into the embryonic thymus. PMID- 1514385 TI - [Bilateral absence of the quadrangular space of the axilla]. AB - In the 1988 student course on gross anatomy dissection of cadavers at Iwate Medical University School of Medicine, two cases of the absence of the quadrangular space of the axilla were found bilaterally in a 92-year-old female who had died of heart failure. The cases were investigated anatomically. The tendons of insertion of the latissimus dorsi and the teres major muscles and the tendon of origin of the long head of the triceps brachii muscle were united, forming a conjoint tendon that attached to the infraglenoid tubercle of the scapula and the lower part of the anatomical neck of the humerus adhering to the articular capsule of the shoulder joint. The subscapularis muscle was normal except that a muscular bundle arose from the conjoint tendon and inserted to the lesser tubercle of the humerus and the crest continuing down from the tubercle. A part of the conjoint tendon was covered by the insertion of the subscapularis muscle, and there was no space between the conjoint tendon and the insertion of the subscapularis muscle. The teres major muscle was poorly developed, but the area of origin was rather wide and arose from both the dorsal and costal surfaces of the scapula. The anatomical features of the latissimus dorsi and the long head of the triceps brachii muscles were normal except for the insertion of the former and the origin of the latter. The triangular space of the axilla was found to be surrounded by the conjoint tendon, teres major muscle, and the lateral border of the scapula covered by the subscapularis and the teres minor muscles.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1514386 TI - Right vertebral artery as the last branch of the aortic arch and a coronary sinus opening into the left atrium as found in a cadaver. PMID- 1514387 TI - [A case of anomalous courses of the brachiocephalic artery, trachea, and esophagus]. AB - A case was described in which the brachiocephalic artery ran transversely in front of the fourth tracheal ring. The abnormal course of this artery may present a possible hazard in the event of a tracheotomy. In this case the anomalous artery was accompanied by a shift of the trachea to the right and of the esophagus to the left. As a consequence, the left recurrent laryngeal nerve ascended in front of the esophagus. The anomalous nerve course may present the possibility of injury to the nerve in the event of a curative operation for esophageal cancer. PMID- 1514388 TI - [Three-dimensional reconstruction of cytoskeletons in rat salivary glands using confocal fluorescence microscopy and volume-rendering computer graphics]. AB - A new reconstruction technique for the demonstration of three-dimensional architectural details from biological fluorescent specimens was used to determine the precise spacial organization of F-actin in rat sublingual glands. F-actin was stained with NBD-phallacidin in thick (20-30 microns) frozen sections and observed with a confocal laser scanning microscope to obtain thin (-1 micron) optically sectioned images. A series of optical sections taken successively at different focal levels in steps of 1 micron was then reconstructed with volume rendering computer graphics. The rendered images viewed from several angles (e.g. top, bottom, sides) clearly revealed the presence of F-actin fluorescence along the hexagonal framework of the junctional complex within the acini and in the cytoplasm of star-shaped myoepithelial cells encircling the acini. The detailed structures and the topographical relations between the junctional complex and myoepithelial cells were more impressively observed when the rendered images were displayed by motion picture. These images are free from any artifacts caused by the mechanical sectioning and revealed well the delicate and complicated profiles of cellular structures that previously have been almost impossible to demonstrate by conventional reconstruction techniques. We expect that the combination of confocal microscopy and volume rendering will permit the dynamic observation of previously unseen phenomena in three dimensions, such as the behavior of biologically active molecules in living cells. PMID- 1514389 TI - [Preparation of skeletal specimens by means of proteolytic enzyme]. PMID- 1514390 TI - [On the processing and maintenance of cadavers for dissecting course]. PMID- 1514391 TI - The whale (Odontoceti) spleen: a type of primitive mammalian spleen. AB - Three spleens from two Odontoceti species were studied histo-anatomically. These spleens consisted of lymphatic nodules, the red pulp (broad sense), and the trabeculo-capsular system composed of the elasto-fibroleiomyocytic tissue. The periarterial lymphatic sheath (PALS) was unclear. Two layers, the intermediate zone and perivenous layer, were distinguishable in the red pulp (broad sense). The perivenous layer was narrow in width and consisted of venules and the intervascular reticular tissue rich in myeloid cells. The collecting and drainage veins were enclosed in this layer. The perivenous layer corresponds to the red pulp (narrow sense) of the common mammalian spleen and may be under involution in a process that probably relates to the remodelling of the intrasplenic vein. The pattern of the arteriovenous communication seemed to be closed, and no ellipsoids were noted around arterial terminals. The Odontoceti spleen has two venous drainage routes (hilar and capsular systems), suggesting a primitive state of evolution, and may be an additional example of the primitive mammalian spleen. PMID- 1514392 TI - [The innervation of deep muscles of the human forearm extensors]. AB - The innervation of four deep muscles of the human forearm extensors (the abductor pollicis longus, the extensor pollicis brevis, the extensor pollicis longus, and the extensor indicis muscles) were investigated in 24 bodies (48 sides) from those used in the 1989 and 1990 student courses in gross anatomy dissection at the Iwate Medical University School of Medicine. The forearm extensor muscles and the deep branch of the radial nerve were dissected intensively in the student courses in gross anatomy and were removed afterwards. The four deep muscles of the human forearm extensors and the nerves innervating the muscles were observed while they were immersed in the water and with use of a stereomicroscope--with the assistance of which they were drawn. In six sides the intramuscular nerve supply was also examined carefully and drawn. The results were as follows. 1. The nerves to the four deep muscles of the forearm extensors arose usually from the deep branch of the radial nerve after emerging the supinator muscle and sending branches to superficial forearm extensors. In some cases a nerve or nerves to the superficial forearm extensors were observed arising from the deep branch of the radial nerve after sending one or more branches to the deep forearm extensor muscles, or from the branches to the deep muscles themselves. However they were split easily from the deep branch of the radial nerve and from the branches to the four deep forearm extensors proximally near to the emerging of the deep branch from the supinator muscle. Therefore, it was considered to be constant that the nerves to the four deep forearm extensors arose from the deep branch of the radial nerve after branching to the superficial forearm extensors. 2. The radial group of the deep forearm extensors (the abductor pollicis longus and the extensor pollicis brevis muscles) was innervated usually by one branch that arose from the deep branch of the radial nerve just after emerging from the supinator and giving off branches to the superficial forearm extensors. This branch ran on the dorsal (extensor) surface of the abductor pollicis longus muscle distally, sending many twigs to this muscle, and entered into the muscle at various distances from the origin (Figs. 1-6). The abductor pollicis brevis muscle was innervated by some twigs that ran usually inside but occasionally outside of the abductor pollicis longus muscle (Figs. 7-10).(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1514393 TI - Factors of importance for changes in dental caries among adults. A follow-up study of Oslo citizens from the age of 35 to 50 years. AB - Eighty-one 35-year-old Oslo citizens examined in 1973 were reexamined after 15 years, to monitor changes in their caries situation expressed as carious surfaces (DS + DFS). Factors considered to be of importance for a change in the number of carious surfaces over this 15-year period were arranged under four items: environment, behavior, human biology, and health care organization. The results showed a slight but not statistically significant increase in the overall caries experience expressed as DMFS. A statistically significant reduction in DS + DFS from the age of 35 to 50 years was demonstrated. Despite this reduction 23% of the 50-year-olds had more carious surfaces than at age 35. The results indicate that the improvement in the number of untreated carious surfaces reported from many Western societies is also valid for adult Norwegians. However, this improvement is not shared by all. Multivariate analyses showed that behavioral factors had the greatest impact on the observed changes in dental health. PMID- 1514394 TI - Numerical density and distributional pattern of dentin tubules. AB - By a new method the numerical density and distributional pattern of transversely cut dentin tubules and the diameters of their peritubular dentin walls were measured in sections near the dentin-enamel junction (DEJ), midway to the pulp, and near the pulp wall in human premolars. For each section the mean and standard deviation of these variables were expressed. At all three levels the measurements comprised the same bundle of tubules from the DEJ to pulp in the coronal dentin. The number of tubules per square millimeter increased more than three times, and the diameters of peritubular dentin decreased one-tenth, whereas central distances between tubules were halved from DEJ to pulp. Thus the pulpward reduction of intertubular dentin is quantified. The distribution of the tubules is not regularly hexagonal, but the distances between them at each given depth are still very uniform in all directions. The pattern of cross-cut tubules often showed distinct short curved rows. The quantitative method might be used to determine taxonomic affinities. PMID- 1514395 TI - Effect of experimental traumatic occlusion on periodontal and pulpal blood flow. AB - Fluorescent microspheres (FM) were used to visualize and semi-quantify flood flow in the periodontal ligament (PDL) and dental pulp during experimental traumatic occlusion of the maxillary and mandibular molar teeth in young rats. At different observation points FM were injected systemically, and the number of FM was counted in serial sections from the jaws in the PDL and pulp of the molar teeth in a fluorescent microscope. Blood flow was related to the number of FM in the tissues and in a reference blood sample. In the early stages an increase in blood flow in the PDL and dental pulp was found on the experimental side compared with the contralateral side. Furthermore, there was an increase in blood flow on both sides of the jaws compared with an unoperated control material. The study thus indicates that a local unilateral occlusal trauma initiates blood flow responses in the total molar dentition in rats. PMID- 1514396 TI - Initial studies on the behavior of salivary proteins at liquid/air interfaces. AB - The mode of adsorption of salivary proteins at air/liquid interfaces was studied by using the drop volume technique to measure the kinetics of surface tension decay of aqueous salivary solutions. Adsorption of salivary proteins from whole saliva was fast, with a plateau value of the surface tension of 43 (+/- 2) mNm-1. As the concentration of saliva was reduced, the plateau value of surface tension increased and was achieved more slowly. The reduction in surface tension of aqueous solutions was larger for salivary proteins than for many other proteins reported. PMID- 1514397 TI - A clinical evaluation of the Optec inlay system. AB - To evaluate the clinical quality of ceramic (Optec) inlays, the inlay production of 10 dentists, served by 3 dental laboratories, was examined independently by 2 calibrated examiners. A total of 57 patients with 205 inlays (mean age, 8.1 months) were examined 1 to 32 months after placement by means of using a slightly modified form of the California Dental Association criteria. Periodontal variables such as plaque index, gingival index, and margin index were also recorded. Eight patients reported postoperative but not persistent hypersensitivity in relation to the Optec therapy. No differences between Optec proximal surfaces and homologous control surfaces were seen with regard to plaque or bleeding on probing. The examination using the CDA criteria showed that 59% of the inlays had a slight color mismatch. Slightly roughened surfaces were most common (86%). As to anatomic form and margin integrity, 24% and 67%, respectively, of the inlays were rated excellent. A difference between the dentist with regard to the clinical quality of the inlay treatment procedure was seen. The present results cannot allow a definitive judgement with regard to the long-term clinical quality of the Optec inlay system but will serve as a base for further studies. PMID- 1514398 TI - Relation of glenoid fossa morphology to mandibulofacial asymmetry, studied in dry human Lapp skulls. AB - Asymmetry in the shape and location of the temporomandibular joint and its associations with mandibulofacial asymmetry were studied in 40 Lapp skulls by a method in which the configuration of the fossa is clearly defined. The results show a general directional temporomandibular asymmetry. The glenoid fossa on the right was on average more laterally and distally placed than on the left when studied in the axial view. The mandible was more often longer on the left than on the right in the frontal view. The temporomandibular asymmetry found here was associated with skull base characteristics and left-right differences in mandibular length. The basic reason for the asymmetric relationships may lie in the reciprocal interaction between the developmental aspects of the skull base and impaired directional function. PMID- 1514399 TI - Swedish dentists' perceptions of their patients. AB - Swedish dentists' perceptions of patient behavior problems, levels of stress experienced by the dentists in relation to such behavior, and general problem areas in their occupational situation were investigated by means of a self administered questionnaire mailed to a sample of 485 Swedish dentists. The questionnaire assessed 16 different patient behavior problems and an additional number of other occupationally related problem areas. A total of 342 replies (71.4%) were analyzed. The relationship between the occurrence of behavior problems and the resulting level of stress was inversely proportional. This implies that Swedish dentists feel confident in dealing with behavior problems in their patients. Furthermore, this study shows that most dentists (93%) feel positive about their work and believe that their work is highly appreciated by their patients (96%) and colleagues (84%). PMID- 1514400 TI - Enzyme inhibitory assay using monoclonal antibody against acid alpha-D glucosidase in prenatal diagnosis to identify homozygotes of Pompe's disease. AB - From January 1985 to January 1990, measurements of acid alpha-D-glucosidase activity in amniocytes or chorionic villus samplings were done for 24 pregnant mothers who were carriers of Pompe's disease. 6 women had two subsequent pregnancies. Amniotic fluid was obtained by transabdominal amniocentesis performed on 10 of them, while chorionic villus samplings were obtained in the other 20. The results showed that 7 (23.3%) cases were homozygotes, 16 (53.4%) cases were heterozygotes, and 7 (23.3%) cases were normal. Pregnancies were terminated in the homozygotic group. Final diagnosis was confirmed by either skin fibroblast culture or clinical course. However, we found that there was overlap in the acid alpha-D-glucosidase activity of amniocytes between homozygotes and heterozygotes due to residual activity of neutral alpha-D-glucosidase. In an attempt to identify heterozygotes for Pompe's disease, we established an enzyme inhibitory assay using monoclonal antibody (mAb) against acid alpha-D glucosidase. Comparing the differences in alpha-D-glucosidase activity before and after mAb treatment the homozygotes were significantly lower than heterozygotes (P less than 0.001). There was no more overlap in the difference of acid alpha-D glucosidase activity before and after mAb treatment between heterozygotes and homozygotes in amniocytes. This modified enzyme inhibitory assay should facilitate homozygote detection. Comparing acid alpha-D-glucosidase activity between CVS and amniocytes, the enzyme activity in CVS is about 5 times higher than in amniocytes. There was no overlap in the acid alpha-D-glucosidase activity between homozygotes and heterozygotes. Therefore, CVS is better than amniocentesis in the prenatal diagnosis of Pompe's disease. PMID- 1514401 TI - Chemotherapy-related side effects in children with acute lymphocytic leukemia in Taiwan: a nursing perspective. AB - The purpose of this study was to understand the pattern of side effects experienced by children with acute lymphocytic leukemia (ALL) who were receiving the induction and consolidation phases of a specific chemotherapy regimen. One hundred and one children with ALL in treatment centers throughout Taiwan in June 1990 through June 1991 served as the sample for this study. Children had been divided into two groups, a standard risk group (SR) and a high risk group (HR), which received different therapeutic regimens. Of 101 children, 52 in SR and 27 in HR completed the induction and consolidation phases of treatment. Among sources of data for the study were nurses' prospective close observations in the natural care setting of each child. Chemotherapy-related side effects are multifaceted and intrusive, including changes in hematopoietic function, body function and body appearance. The most common side effects with regard to body function were elevation of body temperature, ulceration of oral mucous membrane, poor appetite, nausea and vomiting, ulceration of anus, diarrhea, impaired mobility. Side effects were greatest during the first through third weeks of the chemotherapy regimen. Twenty percent of the children developed infection. The findings stressed that nurses should be aware of such patterns of side effects so that they can provide optimal care to patients receiving chemotherapy. PMID- 1514402 TI - [Percutaneous catheterization of internal jugular vein]. AB - Percutaneous catheterization of internal jugular vein has been recognized as a valuable procedure during special conditions which need either a central venous pressure monitoring or a route for intravenous infusion either on a long term or short term basis. In our hospital we had 27 patients who had undergone 32 percutaneous internal jugular vein catheterizations over a period of 19 months. Patients' age ranged from 10 days to 13 year-old. Among these 27 patients, 20 were less than 1 year-old. Overall successful punctures were achieved in 87.5% of attempts. There was no case complicated with pneumothorax, hematoma, air embolization, pericardial tamponade or Horner's syndrome following the procedure. 68.7% of the procedure were done under emergency situation when peripheral venous route were inaccessible. In our experience, this procedure is a highly useful method of obtaining venous line in patient with inaccessible peripheral venous route. PMID- 1514403 TI - Acute myelofibrosis terminating in acute lymphoblastic leukemia: report of one case. AB - A four-year-old boy suffered from acute myelofibrosis which became acute lymphoblastic leukemia during the course of the disease. Histologic and immunophenotypic studies revealed that the leukemic cells were lymphoblasts. Immunophenotypic examination also excluded the possibility of acute megakaryoblastic, monocytic and myeloid leukemia. Thus terminal leukemic transformation, in some cases of acute myelofibrosis, may be of a lymphoid nature. PMID- 1514404 TI - Congenital Horner's syndrome: report of one case. AB - Congenital Horner's syndrome is an infrequent illness caused by a lesion of the cervical sympathetic nerve fiber. It's clinical features are facial anhidrosis, ptosis, miosis, and hypochromia iridis of the affected side. The subject of this report, a full-term male newborn, had had a smooth birth process but was found on the second day of life to have narrowing of the palpebral fissure and absence of facial flushing on the right side when he cried. Ophthalmologic examination revealed a smaller right pupil. The above abnormalities proved to result from a post-ganglionic lesion, after pharmacologic test. Roentgenograms of the skull, chest and cervical spine were normal, and a computed tomography scan of the cervical spine showed no abnormalities. The diagnosis was of congenital Horner's syndrome. Since no congenital Horner's syndrome to the newborn period could be found in previous literature, this report is presented. PMID- 1514405 TI - [Neonatal bowel perforation successfully treated by conservative treatment: report of two cases]. AB - Neonatal bowel perforation is a potentially lethal disease whose etiology and pathophysiology remain unclear. An aggressive approach with surgical intervention has been favored by some authors; otherwise, a high mortality rate was reported. In recent time, peritoneal drainage under local anesthesia for critically-ill premature infants with complicating perforation of necrotizing enterocolitis has had good results. Two cases of such perforation are reported. Case 1, a full-term baby was delivered by spontaneous delivery. Bowel perforation was found on the second day after birth. Case 2, a 27-week gestational age, premature baby, was delivered by emergent Cesarean section because of maternal placenta previa with massive vaginal bleeding. Bowel perforation was found, after feeding, on the seventh day after birth. Both sets of parents refused any surgical procedure, but the infants survived under medically conservative treatment, and the use of peritoneal drainage. This technique may be considered for neonates with bowel perforation if a surgical procedure is unsuitable or unacceptable. PMID- 1514406 TI - An analysis of prognostic factors for submersion accidents in children. AB - The case histories of 47 consecutive pediatric submersion victims admitted to the Changhua Christian Hospital from 1983 to 1990 were retrospectively reviewed for patient status on arrival and eventual outcome. Age, sex, season, location, estimated submersion time, cardiopulmonary resuscitation (CPR) at the scene, vital signs on arrival, Orlowski score, modified physiologic stability index (PSI) scoring system were analyzed. Patient outcome, based on the status at discharge, was categorized as (1) 22 patients survived intact, with normal findings on neurologic examination; (2) 10 patients had neurologic insults, with abnormal neurologic findings including mental retardation; (3) 15 patients died. The results clearly demonstrated that there were no differences among these three groups in the variables of estimated submersion time, CPR at the scene, referral from local medical clinics. The prominent characteristics of pediatric submersion were male (74%), age below three years (64%), summer season (45%) and fishpool (60%). The favorable prognostic factors were a body temperature greater than thirty-five centigrade, detectable heart beat and respiration on arrival, Orlowski score below two and PSI below seven. PMID- 1514407 TI - Electroencephalographic and clinical features of typical absence seizures in children. AB - From July 1986 to July 1991, seventeen typical absence seizures, in patients aged 3 to 12 years (mean: 7 years 1 month), were collected for clinical and electroencephalographic (EEG) analysis. All were first-evaluated patients at the Pediatric Neurology Clinic, National Taiwan University Hospital with thorough EEG examination (including waking and natural sleep records) and detailed medical records. All had no history of any brain insult, except for one who had had febrile convulsion before. There were nine female and eight male patients. All had regular bilaterally synchronous and symmetric 3 Hz spike-and-wave discharges and absences. Nine of the 17 cases had interictal focal spike discharges, located over centro-temporal area in 4 cases, fronto-central area in 2 cases and parietooccipital area in the other 2 cases. Another patient was found to have 3 Hz posterior slow waves. Four of the 17 cases had automatisms. Only one case had photo-paroxysmal response. Hyperventilation could induce clinical spells and typical EEG findings in all 17. Normal interictal background activity on the EEG was also found in all cases. PMID- 1514408 TI - Sinus node dysfunction in children. AB - Seven out of 829 pediatric cardiac patients (0.84%) were found to have sinus node dysfunction (SND) over the past seven years. Of the seven patients, three had structurally normal hearts. One of these three patients had long QT syndrome. In four patients, structural heart disease was noted. In three of these four patients the sinus node dysfunction was attributed to cardiac surgery. The age of onset of SND ranged from four months to eight years. Presenting symptoms and signs included syncope, near-syncope, seizure and congestive heart failure. Two patients were asymptomatic. Five patients had episodic sinus pause. Sinus or junctional bradycardia was noted in four patients. Three had tachy-bradycardia. High grade atrioventricular block was noted in one patient. Treadmill exercise test revealed a nonsustained ventricular tachycardia in two patients. All seven patients were found to have prolonged maximal corrected sinus node recovery time. Prolonged intra-atrial conduction time was found in three, prolonged AV nodal conduction time in one, and prolonged His-Purkinje conduction time in one patient during the electrophysiologic study. All seven patients showed abnormal results in intrinsic heart rate study. Anti-arrhythmic drugs were prescribed. During the follow-up study, no patient died, but two patients received a pacemaker implantation. Because of the extent of their conduction system diseases, it is recommended that patients with SND should be thoroughly investigated. PMID- 1514409 TI - The neonatal morbidity and mortality of low birth weight neonates. AB - During the period between January 1, 1987 and March 31, 1991, a total of 454 low birth weight neonates, classified if below 2,500 grams, admitted to this hospital, 450 of them could be evaluated retrospectively. Among the 450 cases, 41 (9.1%) were transferred from outside hospitals within 24 hours of birth; and 409 were original hospital inpatients. The sex distribution was quite even (M/F = 227/223), but more than half of them were small-for-date (56.4%). Multiple pregnancy accounted for 22.9%, and toxemic mother, for 11.6%. Neonatal mortality rates were 23.9% for those with birth weight below 1,500, and 45.5% for those with birth weight below 1,000 grams, respectively. Respiratory distress syndrome occurred in 15.9% of the low birth weight neonates, and the incidence increased stepwise as birth weight decreased. Symptomatic patent ductus arteriosus could be detected in 11%. Fundoscopical evaluation, a routine for all with birth weight below 1,500 grams or below 2,000 grams with prolonged ventilator support, demonstrated retinopathy of prematurity in 5.6% of all cases or 50% in those below 1,000 grams. Routine brain echo done in all those below 2,000 grams within the first three days of age, and at least once every week thereafter, revealed intracranial hemorrhage in 10.2%, but only 2.4% belonged to grade III-IV. Respiratory distress syndrome and outborn were the two major determinants affecting the severity and occurrence of intraventricular hemorrhage significantly.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1514410 TI - Measurement of urinary orotic acid by gas chromatography-mass spectrometry. AB - Urinary excretion of orotic acid is increased in many inborn errors of ureagenesis and some other diseases. Urine orotic acid is found to be accurately measured by gas chromatography-mass spectrometry (GC-MASS) under the conditions for organic acids analysis. Therefore, GC-MASS analysis of urine is also helpful in the diagnosis of urea cycle disorders in patients with hyperammonemia. Specific tests for orotic acid measurement are not necessary if urine organic acids analysis is available. PMID- 1514411 TI - [Ultrasonic detection of ectopic ureterocele]. AB - Ten cases of duplex kidney with ectopic ureterocele were detected by ultrasound in the recent four years. There were eight girls and two boys. One case was found to have bilateral ectopic ureterocele, the others were unilateral. Urinary tract infection was found in five cases, urinary dribbling was told in one case, and the other four cases were asymptomatic. The age distribution ranged from newborn to 15 years. Six cases received surgery, and the other four cases were followup at O.P.D. In these cases, the sonography could identify the hydronephrotic nature of the upper pole moiety. Dilatation of the upper pole ureter could be demonstrated. A sonolucent intravesical cystic mass also could be outlined. In this series, five cases with residual parenchyma were assessed by ultrasonography, and two cases with pus formation in the upper pole collecting system were detected. On intravenous urogram, the affected upper pole moiety was not or poorly visualized in these cases, thus produced some diagnostic challenges. Ultrasonic examination is an excellent method to identify a fluid filled cystic structure, and can provide a simple and non-invasive technique for confirmation of ectopic ureterocele, which is independent of renal function. Therefore, it has become an important modality in the detection, diagnosis and followup of this anomaly. PMID- 1514412 TI - Immunological study in three families of juvenile ankylosing spondylitis. AB - Three patients, all exhibiting symptoms before 15 years of age, were diagnosed as juvenile ankylosing spondylitis (JAS) by stigma of JAS. The families of these three patients--a total of fifteen first-degree relatives--had clinical, radiologic and laboratory examinations. All three patients and four family members (26%) had positive HLA-B27 and ankylosing spondylitis (AS). Five (33%) of these three family members had positive HLA-B27 but were asymptomatic; six members(40%) were HLA-B27 negative and symptom-free. A high positive rate of HLA B27 was found among the patients (100%) and the family members (60%). The rheumatoid factor, antinuclear antibody, and anti-native DNA antibody were negative for all patients and family members. Significant elevation of IgG, IgA, and C3 were noted in the AS group. The CD3 cell was lower, and the ratio of CD4/CD8 was decreased in the AS group. Lympho-proliferative responses to phytomitogens (Con A, LPS and PHA) were also done in our study. There was no significant difference in Con A and LPS stimulation index among the AS group, symptom-free family members and normal controls. PMID- 1514413 TI - Intracerebral arteriovenous fistula: report of one case. AB - Intracranial arteriovenous fistula (AVF) is rare. Of the 320 arteriovenous malformations (AVMs) treated by Halbach over the past ten years, only five (1.6%) had a single arteriovenous connection. In the present study, a male infant developed focal seizure and intracranial hemorrhage without cardiac decompensation at the age of 42 days. When he was 3 years and 4 months old, status epileptics occurred, and AVF was discovered via CT scan and cerebral angiographic examination. The AVF was fed by a middle cerebral artery and drained into a huge cortical vein over the left parietooccipital area. Endovascular therapy and/or surgery were suggested, but the family refused. Though seizures occurred occasionally, the patient's consciousness level had become more clear, and he was discharged after three weeks' hospitalization. The patient was noted to be lethargic and only could roll over partially at the age of 3 year and 8 months, in the latest follow-up. PMID- 1514414 TI - Atypical Kawasaki disease: report of two cases. AB - Two cases of atypical Kawasaki disease are reported. Case 1 was a five-month-old male infant admitted to this hospital with a 10-day's history of high fever. On examination, he appeared ill-looking and only hepatomegaly was noted. Laboratory studies showed leukocytosis, thrombocytosis, elevated ESR and pleocytosis in CSF. He was treated as sepsis with meningitis. Sudden death occurred on the eighth day of admission, and left coronary artery aneurysm with thrombosis was noted at autopsy. Case 2 was a four-month-old male infant referred to our hospital with fever and cervical lymphadenopathy of 11 day's duration, and unresponsive to antibiotics. Skin rash had developed after oxacillin injection. Echocardiogram, performed on the third day of admission, disclosed a 5-8 mm aneurysm of the left coronary artery and a 4 mm aneurysm of the right coronary artery. Before a specific diagnostic test for Kawasaki disease becomes available, we suggest that a possible diagnosis of Kawasaki disease and echocardiographic evaluation should be considered in case of (1) presence of partial criteria of Kawasaki disease with thrombocytosis; and/or (2) young infants with prolonged unexplained fever. PMID- 1514415 TI - Marinesco-Sjogren syndrome: report of one case. AB - A three-year-old Taiwanese boy with Marinesco-Sjogren syndrome is reported. Psychomotor retardation had been noticed since early infancy with hypotonia, muscle weakness, delayed motor milestones and imbalance in sitting and standing. Bilateral visual impairment proved to be congenital cataract. Speech was limited to a few words. The parents were consanguineous, and there are two similarly affected siblings. The brain computed tomography revealed cerebellar atrophy. The evoked potential studies indicated a central origin or brainstem lesion. The histopathologic study of the muscle showed variation in fiber size and regenerating fibers. The patient received intraocular lens implantation and was discharged under a home rehabilitation program. PMID- 1514416 TI - G syndrome: report of two cases. AB - This report concerns two cases of G syndrome in male neonates with hypertelorism, hypospadias and hoarse/voiceless cry. Case 1 had a positive family history; all similarly affected relatives have apparent hypertelorism. Case 2 seemed to represent a new mutation, since the parents are apparently normal, and the family history was non-contributory. The clinical expression of Case 1 was relatively severe and needed further surgical management, such as imperforate anus, hypospadias, and vesicoureteral reflux. Case 2 had two manifestations not previously reported: hypoplasia of cerebellum and web neck. PMID- 1514417 TI - Liveborn trisomy 22: report of one case. AB - A case of trisomy 22 liveborn female baby with multiple congenital anomalies is described. Physical manifestations included failure to thrive, hypotonia, pre auricular sinus, low set ears, hypertelorism, posterior low hair line, micrognathia, cleft palate, congenital heart disease, imperforated anus with anovulvar fistula, contracted pelvis and bilateral rocker-bottom feet. The infant died at two months of age. Cases of trisomy 22 usually present with many severe malformations, and they rarely survive to term. A review of the literature is presented to delineate this chromosome disorder. PMID- 1514419 TI - A survey of more than 90 commercially available luminometers and imaging devices for low-light measurements of chemiluminescence and bioluminescence, including instruments for manual, automatic and specialized operation, for HPLC, LC, GLC and microtitre plates. Part 2: Photographs. AB - Part 1 of this survey comprised a description of the luminometers (J. Biolumin. Chemilumin. 7, 77-108 (1992)) and was compiled in January and February 1992 from information available in public domain literature requested by and supplied to the author by numerous companies in the previous two months. This part includes photographs of around 40 of these instruments. It is intended that updates to this review will be published at least annually in this journal and suppliers are invited to provide full technical details of new luminometric equipment to the author. PMID- 1514418 TI - [Infantile bilateral necrosis of the striatum of corpus: report of four cases]. AB - The designation of "Infantile Bilateral Striatal Necrosis" (IBSN) was first given by Friede in 1975. However, this unusual condition was first described by Paterson and Carmichael in 1924. The disease is rare with uncertain etiology. The clinical picture includes choreoathetosis, abnormal eye movements, seizures and mental dullness. These circumstances often follow symptoms such as fever, vomiting and impaired consciousness. The final diagnosis is confirmed by pathological examination, which reveals symmetrical degeneration of bilateral basal ganglia. With present technology IBSN can be well demonstrated in the brain Ct scans or MRI scans nowadays. This article reports four cases with clinical manifestations which had appeared before the age of one year. Three cases had prodromal upper respiratory tract infection symptoms with vomiting, while seizure and impaired consciousness ensued. One case had several bouts of pneumonitis followed by seizures, impaired consciousness and abnormal eye movement. Brain sonogram of one of these cases showed hyper-echoic basal ganglia, while CT scans or MRI scans revealed symmetrical hypodensity or signal change over bilateral basal ganglia, respectively. All of these led to a bedridden life. These four cases are reported based on their clinical presentations and brain imaging findings, in spite of the absence of pathological confirmation. Some of the literature are also reviewed. To sum up, IBSN should be kept in mind in the differential diagnosis of symmetrical bilateral basal ganglia lesion after the exclusion of other disorders such as neurometabolic disorders, central nervous system infection, carbon monoxide intoxication, hypoxic-ischemic encephalopathy, tumors and cerebrovascular disorders etc. PMID- 1514420 TI - Light-induced biophotonic emission from plant tissues. AB - The emission of biophotons in the visible range, following a delay time of 2-200 seconds after exposure to light, has been measured in germinating seeds, roots, flowers, leaves, and cells. It was found that the biophotonic signals are reproducible and light-induced. The observed signals from germinating seeds of Phaseolus aures and decaying leaves of Eucalyptus are presented to show that the signals have characteristic kinetics and intensity. The kinetics of the signal was found to be independent of the stage of growth or decay, though its intensity varied with biological factors. The kinetics in the first minute is characterized by a single exponential decay term while that in the region t less than or equal to 200 s is characterized by two exponentials. The variation in the intensity of the signal with mass, state of hydration, and growth, and the effect of inhibitors in various systems (e.g. leaves, lichen, Chlorella) are reported. PMID- 1514421 TI - Comparison of properties of commercially available crystalline native and recombinant firefly luciferases. AB - Commercially available crystalline native and recombinant firefly luciferases were compared. The two types of luciferase had indistinguishable responses to variation in ATP and luciferin concentrations and to omission of reaction components. The time courses of light production, the responses to nucleotide analogues, and the stability of the enzymes under several storage conditions were identical. The native enzyme had a slightly greater specific activity and was more sensitive to trypsin degradation. These differences are probably attributable to differences in conformation. PMID- 1514422 TI - Bioluminescence and chemiluminescence literature--nucleic acid hybridization assays. PMID- 1514423 TI - CSF drainage in patients with posterior fossa tumours. AB - The management of hydrocephalus secondary to a posterior fossa tumour is controversial. We audited recent practice with a retrospective analysis of 287 consecutive patients undergoing posterior fossa exploration for tumour. 85 shunts and 112 external ventricular drains (EVD) were placed. The overall CNS infection rate in the series was 6%. There was a significantly higher (p less than 0.01) infection rate in patients who had a drainage procedure, and a trend towards higher infection rates in patients with two drainage procedures. Early infection rates with EVDs and shunts were the same (7%). One third of patients with hydrocephalus had pre-operative drainage, a third had per-operative drainage but only a quarter required a permanent shunt. The majority of patients will not require a permanent shunt and where temporary CSF diversion is required EVD is reasonable. PMID- 1514424 TI - Does the shunt opening pressure influence the effect of shunt surgery in normal pressure hydrocephalus? AB - Thirteen patients with normal pressure hydrocephalus were operated upon with an externally maneuverable shunt system (Sophy SU8) in order to investigate its influence on clinical outcome, intracranial pressure and cranial CT parameters. The opening pressure was set at high at surgery and lowered stepwise at intervals of three months to medium and low. The clinical condition, intracranial pressure and cranial CT parameters were examined at the end of the 3 months interval on each pressure level. The patients improved within the first 3 months inspite of an unchanged mean intracranial pressure and remained in a stable clinical condition during the rest of the study period. The intracranial pressure was significantly reduced at 9 months. The ventricular index, Evans index, temporal horn and third ventricle width were reduced 3 months post-operatively and did not change significantly during the rest of the study. The pre-operative third ventricle width was correlated to high psychometric test results after shunt surgery. Reduction in ventricular index, Evans index and third ventricle width after surgery correlated to improvement in psychometric scoring. The clinical improvement after shunt surgery for normal pressure hydrocephalus is seen within 3 months and is independent of the adjusted valve pressure. PMID- 1514426 TI - Histopathological evaluation of polymethyl methacrylate as an embolic agent. AB - Polymethyl methacrylate (PMMA) microspheres were used as an embolic agent to reduce the vascularity in eight patients with intracranial vascular tumours. Post embolization angiograms showed 30-60% reduction in the vascularity of the tumours. No patient developed any neurological complications in the immediate post-embolization period. These eight patients subsequently underwent surgery for the removal of their tumours. During surgery there was minimal blood loss and a good plane of cleavage was obtained between the tumour and the adjacent brain. The surgical specimens were examined histopathologically for the effects of PMMA. PMMA microspheres, in contrast to other cyanoacrylates--isobutyl-2-cyanoacrylate (IBCA)--did not elicit either inflammatory reaction or mural angionecrosis within the wall of the embolised vessels. The histopathological studies suggest that PMMA microspheres are an inert material and can be used as an adjunct in the management of intracranial vascular tumours. PMID- 1514425 TI - Management of giant serpentine aneurysms of the middle cerebral artery--review of literature and report of a case successfully treated by STA-MCA anastomosis only. AB - Thirty-eight cases of giant serpentine aneurysms (GSA), including 17 GSA of the middle cerebral artery (MCA), were reviewed in the literature. The treatment possibilities of GSA of the MCA are discussed together with our own case who was a 39-year-old male with a GSA of the right MCA and was treated only by STA-MCA anastomosis. The pathogenetic mechanism of progressive enlargement of the aneurysm is also discussed. PMID- 1514427 TI - ICP dependent changes of CSF outflow resistance. AB - CSF outflow resistance was studied in cats using the lumbar infusion tests. Different infusion rates were applied from 0.012 to 1.8 ml/min. ICP level obtained during infusions varied from 8.9 +/- 3.0 to 144.0 +/- 25.7 mmHg. The calculated resistance (R) values were within 75.2 +/- 14.4 to 255.6 +/- 71.2. mm Hg/ml/min. The relation between ICP and R are characterized by a curve which can be divided into three parts. First R rises until an ICP level of about 20 mmHg is reached, then R decreases fast until the ICP value is about 50 mmHg, a further drop is much slower and the ICP/R curve becomes almost parallel to the ICP axis. The possible reasons for the ICP dependent changes of R as well as the clinical importance of the results obtained are discussed. PMID- 1514428 TI - The course of vasospasm following subarachnoid haemorrhage in rats. A vertebrobasilar angiographic study. AB - The course of vasospasm following subarachnoid haemorrhage in rats was studied using vertebrobasilar angiography. Wistar and Sprague Dawley rats were compared with respect to vasospastic response after bleeding. A more pronounced vasospasm was found in Sprague Dawley rats. In order to avoid a possible toxic effect on the contrast medium, only one angiogram per animal was initially performed. However, a comparison with the results obtained in a separate series of non challenged animals demonstrated a difficulty due to high variability in basilar artery size in the latter group. Therefore, vasospasm can be more readily shown if multiple angiograms are used in the same animal so that the vasospasm can be expressed as a percentage of the initial diameter of the basilar artery. It was found that multiple angiograms are well tolerated when non-ionic contrast media are used. PMID- 1514429 TI - Collagen vicryl--a new dural prosthesis. AB - No ideal dural grafting material is currently available. Many materials have been evaluated in this role, and for many neurosurgeons cadaveric human lyophilized dura has been popular. Recently this material has been putatively associated with Creutzfeldt-Jakob disease. In this study we compared three degradable materials, collagen vicryl (Bovine collagen coated vicryl mesh), Zenoderm (Porcine dermis) and Lyodura (Lyophilized human cadaveric dura) as dural substitutes. In an experimental model using the New Zealand White Rabbit the materials were implanted into dural defects of dimensions 1.7 cm by 1 cm. In the control group the dura was not repaired. In total 47 animals were used and sacrificed at time intervals of 2, 4, 8, 12, and 24 weeks. On gross examination the collagen vicryl produced few adhesions to the cerebral cortex and was replaced by a neomembrane which showed good union with the host dura. In the control group no new layer was formed and there were severe cortical adhesions. Zenoderm and Lyodura remained undegraded and produced more adherence to the cerebral cortex than the collagen vicryl implant. The histological examination showed collagen vicryl to support ingrowth of fibroblasts and the production of a new collagen layer which by 3 months resembled the original host dura. The inflammatory response to the implant did not persist after 3 months. The other substitutes were revitalized by host cells but remained undegraded at 6 months with ingrowth of woven bone and persistence of inflammatory and foreign body response. The results show collagen vicryl to be a suitable dural substitute with potential advantages over other currently used degradable materials, and should be evaluated more fully, both in laboratory studies and clinically. PMID- 1514430 TI - Intra-operative monitoring of the facial nerve with an air inflated balloon. Technical note. AB - A simple, reliable and cheap device for intra-operative monitoring of the facial nerve during surgery for cerebellopontine angle tumours is presented. It consists of a single use tracheostomy tube with a low pressure air inflatable cuff placed in the mouth of the patient on the side of the tumour, connected by a pressure transducer to a monitoring unit. It records any pressure changes in the patient's mouth induced by muscular contractions as a result of excitation of the inferior parts of the facial nerve. PMID- 1514431 TI - A ring electrode to record extraocular muscle activities during skull base surgery. AB - A ring-shaped electrode was developed and used in 20 patients to record evoked electromyographic responses directly from the extraocular muscles during skull base surgery. Intra-operative monitoring with this electrode helps the surgeon to localize the nerves that innervate the extraocular muscles precisely and to refrain from disturbing important neural structures during operations. Such monitoring also provides some insight into the pathophysiology of the dysfunction of these nerves resulting from skull base lesions. PMID- 1514432 TI - Slit ventricle syndrome in children: clinical presentation and treatment. AB - Symptomatic ventricular coaptation, or the slit ventricle syndrome, is frequently described and recognized as a clinical entity in the pediatric population. It is characterized by symptoms of shunt failure (i.e., ataxia, obtundation, nausea, vomiting, lethargy, irritability, and complaints of headache) and the CT findings of ventricular coaptation (slit-like ventricles). This study of twenty-two children with this syndrome reflects the variety of possible clinical presentations, and the variety of available treatment modalities. Multiple therapeutic approaches were required in seven of the patients. This illustrates not only an evolving treatment regimen, but also that a single treatment modality is not universally effective. Six patients needed only occasional symptomatic support. Blockage and/or removal of the shunt system was the definitive therapy in six patients, pressure augmentation in nine patients, and subtemporal craniectomy in one. This article outlines the theoretical pathophysiology, and a scheme for the management of patients with this syndrome. PMID- 1514433 TI - Abscess formation in Rathke's cleft cyst. AB - Two patients are discussed who presented at our Institute with endocrine dysfunction and sellar enlargement. CT scans revealed intra and suprasellar expanding lesions with ring enhancement. The postoperative histological examination showed remnants of Rathke's cleft cyst together with signs of inflammation. CT and MRI pictures, and possible mechanisms of abscess formation in this region are discussed. PMID- 1514434 TI - A pineal tumour with features of "pineal anlage tumour". AB - A primitive tumour of the pineal region in a 9 month-old boy caused hydrocephalus, ataxic gait and paraplegia leading to death after 9 months of evolution. Histological and histochemical examination revealed a pinealoblastoma with melanotic cells as well as cartilaginous formations. The leptomeningeal seeding of the tumour showed neuroblastic and neuronal differentiation. A diagnosis of pineoblastoma with neuroepithelial and ectomesenchymal differentiation was made. This tumour belongs to a recently defined category of pineal tumours, called pineal anlage tumours. PMID- 1514435 TI - The amniotic fluid compartment: the fetal habitat. AB - This study begins with a phylogenetic overview of the fetal membranes in terrestrial vertebrates. It is, of course, well known that the human amnion differs very little from that of other recent members of the phylum, although during evolution the development of the placenta has brought about extensive changes in the chorion. Much of the structure and many of the functions of both the amnion and chorion laeve can be interpreted from a comparative point of view (e.g., production of lipids). The next section deals with the ontogeny of the human amniotic sac, and the histogenesis and functional structure of the fetal membranes. It concludes with a structural analysis of the single layers of the fetal membranes at the end of pregnancy. Light and electron microscopy and histochemical examination are combined with experimental investigations; the striking differences and departure from any possible "norm", however, made the interpretation of morphological findings particularly difficult. Explanations for these differences are put forward: the texture of the connective tissue elements is only approximately determined and therefore gives rise to many irregularities; differences in the structure of cells depend upon their functional state; and the cells exist in groups which reciprocally exchange functional activity with each other. It is emphasized that the amniotic epithelium produces lipids which then appear in the same composition in the amniotic fluid. The fibroblasts in the amniotic connective tissue may, when necessary, be transformed into phagocytes (the so-called Hofbauer cells). Within the fetal membranes one can also observe glucose metabolism which, apart from the supply of local energy and the storage of glycogen, is concerned with production of phospholipids, triglycerides, glycoproteins, proteoglycans, and collagen (types I, III, and IV). A similar process of glucose metabolism is found in the trophoblast, especially the building-up of an extracellular matrix (the so-called fibrinoid), which seems to play a part in the formation of an immune barrier. An attempt is made to correlate the various differentiated cells of the trophoblast with particular functions. The vacuolated cells obviously store glucose. Others, as lectin binding investigations have shown, are concerned with production of the extracellular matrix. They produce a three-dimensional latticework between the cells, and reach out as far as the borders of the chorionic connective tissue. In this regard, the microtexture of the amniotic and chorionic connective tissue provides a basis for a more precise understanding of their mechanical stability.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1514436 TI - Therapies for hepatitis B virus: current status and future possibilities. AB - Alpha-interferon is the first agent with proven therapeutic efficacy in humans with chronic HBV infection. Obviously, further research is needed to clarify and expand the role of interferon in this setting. In addition, an overall response rate of less than 50% illustrates the need for continuing innovation in the treatment of HBV infection especially in patients with predictors of poor outcome. Despite the advent of effective vaccines against HBV, this pathogen is likely to remain a source of serious human morbidity and mortality for the foreseeable future. Continuing efforts must be directed towards finding more effective therapies against HBV. A recent preliminary report suggests that thymosin. like interferon on immune modulator, may also be efficacious in the treatment of chronic HBV and deserves further study. PMID- 1514437 TI - A preliminary report of a controlled study of thymosin alpha-1 in the woodchuck model of hepadnavirus infection. PMID- 1514438 TI - Delta virus as a vector for the delivery of biologically-active RNAs: possibly a ribozyme specific for chronic hepatitis B virus infection. PMID- 1514439 TI - Drugs as molecular tools. PMID- 1514440 TI - Cellular metabolism and enzymatic phosphorylation of 9-(2-phosphonylmethoxyethyl) guanine (PMEG), a potent antiviral agent. PMID- 1514441 TI - Effect of herpes simplex virus type 1 infection on cytokine gene expression in activated murine peritoneal macrophages. AB - The intrinsic resistance to herpes simplex virus type 1 (HSV-1) of murine peritoneal macrophages (PM phi) obtained after in vivo infection of different stimuli has been investigated and shown to vary depending on the state of M phi activation. Activation of M phi by C. parvum (CP-M phi) or by an avirulent strain of S. typhimurium (Sal-M phi) increased the permissiveness of M phi to HSV-1 infection as evidenced by increased HSV-1 immediate early (IE) gene expression, synthesis of IE proteins, and the degree of cytopathic effect. HSV-1 infection was also found to sharply reduce the level of IL-1-beta mRNA in CP-M phi) and Sal M phi, and the level of IL-3 mRNA in infected Sal-M phi, as measured by northern blot hybridization. Barely detectable levels of IL-beta mRNA were found in Sal-M phi after infection with HSV-1 when the polymerase chain reaction (PCR) assay was used to confirm the reduction of IL-1-beta mRNA. These data suggest that HSV-1 infection can modulate gene expression of some cytokines in the activated M phi. PMID- 1514442 TI - Diagnostic virology--then and now. AB - In the past five years, technologic advances in the shell vial assay and expanding availability of rapid membrane EIA tests have allowed over 90% of the viruses detected in our laboratory to be reported within 24 h postinoculation. PCR technology promises to add a new practical dimension to diagnostic virology especially for the detection of viruses in CSF, tissues, and blood. Extension of these diagnostic capabilities from investigative protocols to general laboratories for routine use will be our biggest challenge and be based on considerations of cost, licensing, and availability of this technology in "kit" formats. PMID- 1514443 TI - DNA probes for viral diagnosis. PMID- 1514444 TI - Genetically engineered bacteria to identify and produce anti-viral agents. AB - We have prepared a strain of Escherichia coli that expresses both the HIV protease and a Tet protein which has been modified to contain the HIV protease recognition sequence. When the protease is expressed, the bacteria will not grow in the presence of tetracycline. However, when the protease is inhibited the bacteria can grow in tetracycline containing media (Block and Grafstrom 1990). We have selected spontaneously arising Tet resistant mutants and have screened them for those that could be producing an inhibitor of HIV protease. The problems in the construction of this strain and the characterization of the various Tetr mutants are discussed. PMID- 1514445 TI - Antiviral agents from novel marine and terrestrial sources. PMID- 1514446 TI - Therapeutic strategies employing CD4, the HIV receptor. PMID- 1514447 TI - Molecular characterization of HIV-2 (ROD) protease following PCR cloning from virus infected H9 cells. AB - A 450 nucleotide sequence corresponding to the nucleotides 1931-2380 of the viral genome (8) was amplified by polymerase chain reaction (PCR) using template DNA prepared from HIV-2 (ROD) infected H9 cells. The sequence codes for HIV-2 protease and its N-terminal flanking peptide. An identical DNA sequence was obtained from three independent PCR amplifications, which differs from the published sequence of HIV-2 (ROD) in 7 nucleotides scattered throughout the region of the cloned DNA. The cloned DNA was expressed in E. coli cells and resulted in the synthesis of a correctly processed HIV-2 protease, which is enzymatically active. Therefore, none of the seven nucleotide changes, which resulted in two amino acid substitutions, affect the autoproteolytic or trans cleaving activities of the HIV-2 protease. PMID- 1514449 TI - Use of amiodarone for elderly patients. PMID- 1514448 TI - Catalytic antisense RNA (ribozymes): their potential and use as anti-HIV-1 therapeutic agents. PMID- 1514450 TI - Analysis of the diminished skin perfusion in elderly people by laser Doppler flowmetry. AB - Clinical observations suggest an age-associated decline in skin perfusion but there are few quantitative in vivo data on skin perfusion at various ages. We studied skin perfusion of the dorsum of the foot by determining the capillary blood flow velocity (CBFV) expressed in millivolts (mV), using laser Doppler flowmetry, in ten young and 12 elderly men. Our data revealed that, at 32 degrees C skin temperature, the CBFV oscillations (vasomotions) are of higher median amplitude in young people than in elderly subjects: 9.4 mV (95% CI, 8.8-10.0 mV) and 4.6 mV (95% CI, 4.1-7.4 mV), respectively (p less than 0.05). The vasomotion frequency was similar in both age groups. At 44 degrees C skin temperature, the median CBFV peak in the young was 163 mV (95% CI, 128-192 mV), as opposed to 102 mV (95% CI, 92-124 mV) in the aged subjects (p less than 0.0005). The median increment in CBFV, driven by every heart beat, was also higher in the young age group: 86 mV (95% CI, 76.4-96.0 mV) compared with the elderly group: 63 mV (95% CI, 50-72 mV, p less than 0.005). Considering the fact that the magnitude but not the pattern of skin perfusion varied between the two groups, we conclude that ageing is associated with loss of capillary plexus functional units, and therefore the skin perfusion is lower in aged people. PMID- 1514451 TI - Gait on a shoestring: falls and foot separation in parkinsonism. AB - A novel device for monitoring gait, which can be used in confined spaces, is described. In addition to distance/time assessment of gait, it measures foot separation whilst walking. A field trial illustrates its potential in the investigation of falls. PMID- 1514452 TI - Nosocomial diarrhoea due to a single strain of Clostridium difficile: a prolonged outbreak in elderly patients. AB - An outbreak of diarrhoea occurred in an acute geriatric ward of a hospital (A). It affected six patients initially and was found to be due to a single strain of Clostridium difficile. There was little evidence for asymptomatic carriage of this strain or others in the hospital patients. The following three months saw an increase in the number of symptomatic cases of C. difficile disease in two peripheral hospitals, B and C. Patients had been moved from the outbreak ward to these hospitals. Of 18 cases in hospital B all 15 isolates saved for typing were of the 'outbreak' strain. Of three cases occurring in hospital C, only one was the 'outbreak' strain (a relapsed patient who was part of the original episode). There were seven further cases in geriatric and medical wards of hospital A. All six typed isolates were also the outbreak strain. By chance, four isolates from hospital A and four from hospital B pre-dating the outbreak were also available for typing and seven of these were found to be identical to the outbreak strain. This suggests that one strain of C. difficile was endemic in geriatric and medical facilities on two sites and was responsible for nosocomial diarrhoea over at least one year. The problems of optimal management and infection control in this situation are discussed. PMID- 1514454 TI - Life satisfaction in elderly Nigerians: reliability and factor composition of the life satisfaction Index Z. AB - Life satisfaction Index Z was administered to 945 persons aged 60 years and over in a community survey in rural and urban locations in South-Western Nigeria. Life Satisfaction Index scores correlated significantly with items on self-assessed health, loneliness, sex (women having a higher mean score) and location. Items that measure social contact, such as marital status, proximity of nearest child, and frequency of seeing close friends, did not correlate at a significant level. Factor analysis produced two factors on varimax rotation and an internal consistency value of 0.72 was obtained. These values are similar to some of those reported in other studies outside Africa. PMID- 1514453 TI - Radiographic pulmonary changes of gastro-oesophageal reflux disease in elderly patients. AB - The aim of this study was to investigate the association of gastro-oesophageal reflux disease (GORD) with radiographic pulmonary changes. One hundred and thirty seven patients aged over 60 years referred for endoscopy for abdominal symptoms were included in the study. In patients with any suspicion of GORD (n = 95), 24 hour oesophageal pH monitoring was carried out. All the patients were interviewed before the examinations. Chest radiography was performed in all patients. Odds ratio of respiratory symptoms was 8.7 (95% confidence interval 3.4-22.4) in patients with total reflux time of more than 10% compared with those who had total reflux time of less than 10%. In chest radiography, bilateral pleural adhesions and thickenings and bilateral parenchymal scars were significantly more common in patients with, than in those without, regurgitation or large hiatal openings. The occurrence of bilateral scars and pleural thickenings increased with the extent of gastro-oesophageal reflux in pH monitoring. Odds ratios of bilateral pleural thickening and pulmonary scars were 3.1 (95% confidence interval 0.8-11.5) and 5.8 (1.1-29.6) in patients with total reflux time over 10%, compared with patients who had normal total reflux time. The findings indicate that respiratory involvement is a characteristic feature of GORD in elderly patients. PMID- 1514455 TI - Sleep-disordered breathing in elderly people and subjective sleep-wake disturbance. AB - Sleep-disordered breathing and subjective reports of sleep-wake disturbances are both common in elderly people but previous studies investigating the relationship between the two have produced uncertain results. We hypothesized that there is no relationship between sleep-disordered breathing and subjective reports of sleep wake disturbance. Ninety-three random-sampled retirement-village residents, mean age 77.6 years, were monitored overnight with a portable microprocessor-based system. The respiratory disturbance index (RDI) was used as a measure of sleep disordered breathing. Subjects were interviewed regarding sleep-wake patterns and snoring history and the Mini Mental State Examination, Geriatric Depression Scale and Nelson Adult Reading Test were administered. The sleep-wake responses were entered into a principal components analysis. Two components, reflecting night time and daytime disturbance, accounted for 34% of the variance. Multiple regression analyses were performed using RDI as a continuous dependent variable, and three predictor variables, night-time, and daytime disturbance and history of snoring. Together, these variables accounted for only 2% of the variance. We conclude there is no relationship between mild and moderate sleep-disordered breathing and subjective sleep-wake disturbance in this population. PMID- 1514456 TI - Exocrine pancreatic insufficiency in presumed healthy elderly subjects. AB - A pilot study on exocrine pancreatic function, using the 2-day para-aminobenzoic acid (PABA) test, was performed on 21 healthy elderly and 26 healthy young subjects. A PABA excretion index (PEI) less than 55%, indicating moderate to severe exocrine pancreatic insufficiency (EPI), was found in 19% of the elderly group (95% confidence limits 5-42%). While the mean value of the PEI was significantly lower in the elderly compared with the young group (Mann-Whitney Z = 2.8, p less than 0.01), there was no significant difference when the elderly subgroup with PEI less than 55% was excluded. There was no evidence of a generalized moderate to severe decline in pancreatic exocrine function with increasing age; a mild to moderate decline cannot be excluded. PMID- 1514457 TI - Fluid balance in elderly patients following acute stroke. AB - We studied the relationship between plasma osmolality, arginine vasopressin (AVP), and fluid input in patients during the acute phase of a first stroke. Fifteen consecutive patients were studied (median age 79) and their blood sampled on days 0, 1, 2, 3, 7 and 14. Plasma osmolality was related to fluid input over days 0-3 (p = 0.0013) and AVP over 14 days (p less than 0.001). Patients with a poor outcome had higher AVP concentrations (p = 0.02). Those on intravenous fluids received a higher volume (p less than 0.01) and had a lower plasma osmolality (p = 0.04). The results of this preliminary study indicate that a standard regime for fluid input is inappropriate. PMID- 1514458 TI - The relationship of muscle and bone loss and activity levels with age in women. AB - Quadriceps strength and cross-sectional area (CSA), spine bone mineral density (BMD), bone mass in the mid- and distal femur and physical activity levels were measured in 216 healthy British women. Muscle strength, CSA and bone in the distal femur decreased linearly from the third decade. Cortical bone at mid-femur was maintained until the sixth decade. Spine BMD decreased from the fourth decade with an accelerated period of loss in the sixth decade. There were significant positive relationships between quadriceps strength and bone mass at all three skeletal sites. With age kept constant, physical activity levels did not correlate with any of the muscle or bone indices. The force-generating capacity of the quadriceps decreased with age. These results suggest a relationship between the loss of muscle and bone with age which cannot be explained by declining physical activity levels. PMID- 1514459 TI - Inappropriate medication is a major cause of adverse drug reactions in elderly patients. AB - To determine the extent to which adverse drug reactions (ADRs) in elderly patients admitted to hospital are due to inappropriate prescribing, we examined 416 successive admissions of elderly patients to a teaching hospital. Interacting drug combinations and drugs with relative contra-indications (CIs) were common, but not as important in producing ADRs as drugs with absolute CIs or unnecessary drugs. Forty-eight patients (11.5% of admissions) were taking a total of 51 drugs with absolute CIs (3.8% of prescriptions). One hundred and seventy-five drugs were discontinued on or shortly after admission in 113 (27%) patients because they were deemed to be unnecessary. One hundred and three patients (27.0% of those on medication) experienced 151 ADRs of which 75 (49.7%) were due to drugs with absolute CIs and/or that were unnecessary, a significantly higher rate of ADRs (p less than 0.001) than observed for all prescriptions. Of 26 (6.3%) admissions attributed to ADRs, 13 (50%) were due to inappropriate prescriptions. The admission rate per prescription was significantly higher (p less than 0.001) for inappropriate than for appropriate drugs. We conclude that much drug-related morbidity in the elderly population may be avoidable, as it is due to inappropriate prescribing. PMID- 1514460 TI - Autonomic cardiovascular responses to tilting in patients with Alzheimer's disease and in healthy elderly women. AB - The cardiovascular responses to tilting and breathing were studied in 24 patients with late-onset Alzheimer's disease (AD) and 54 healthy control women aged between 75 and 96 years in order to study the parasympathetic and sympathetic heart-rate control. The cardiovascular response to tilting and breathing showed no age-associated decrease in the healthy control women. During rest, the AD patients had lower mean systolic and diastolic blood pressure but the same heart rate as the control patients. After tilting, the AD patients had a greater increase in heart rate, and the mean systolic blood pressure fell to 126 mmHg compared with 160 mmHg in the control women (p less than 0.001). After the initial acceleration, the following deceleration of the heart rate, an expression of parasympathetic nervous activity, was lower in the AD patients (p less than 0.001). The deep-breathing test showed no significant difference between the two groups, but the changes of acceleration and brake indices could indicate a dysfunction of the autonomic nervous system since the AD patients were not recumbent. PMID- 1514461 TI - Interpreting literature on abortion. PMID- 1514462 TI - 'Gateway drugs'. PMID- 1514463 TI - Otitis media. PMID- 1514464 TI - Otitis media. PMID- 1514465 TI - Outpatient use of racemic epinephrine in croup. PMID- 1514466 TI - A family health care system. PMID- 1514467 TI - Euthanasia and assisted suicide: how should physicians respond? PMID- 1514468 TI - Diary of a week in practice. PMID- 1514469 TI - Diagnosis and treatment of croup. AB - Croup is a common childhood disease that has no specific diagnostic test. It must be differentiated from life-threatening diseases, such as epiglottitis, that demand specific interventions. A high degree of toxicity, the presence of dysphagia and the absence of cough help distinguish epiglottitis from croup. The usefulness and safety of visualization of the epiglottis in patients with croup are controversial. Clinical recognition of respiratory distress and failure is vital. Hypoxia is common. Pulse oximetry is helpful in the assessment of hypoxia, but readings do not correlate with clinical status or respiratory failure. Although studies have not proved that mist therapy is beneficial, the efficacy of racemic epinephrine is well documented. High dose corticosteroids have proved effective in the treatment of croup. Outpatient use of racemic epinephrine and steroids remains controversial. PMID- 1514470 TI - Laryngeal tuberculosis revisited. AB - Although a rare entity, laryngeal tuberculosis must be a diagnostic consideration -along with laryngeal carcinoma--whenever patients present with prolonged hoarseness or painful dysphagia. This form of tuberculosis was once thought to be especially virulent and more infectious than other forms; however, severity was probably the result of the frequent association with advanced cavitary disease. Laryngeal tuberculosis usually responds well to multiple-drug antituberculous therapy. PMID- 1514471 TI - Saline amnioinfusion for relief of variable decelerations. AB - Fetal distress due to oligohydramnios can be treated with saline amnioinfusion. The technique is easily learned by physicians who know how to use intrauterine pressure catheters. Therapeutic and prophylactic indications for saline amnioinfusion include oligohydramnios, thick meconium-stained amniotic fluid, and fetal distress. Family physicians can use this new procedure to actively manage labor. PMID- 1514472 TI - Pressure ulcers in adults: prediction and prevention. Agency for Health Care Policy and Research. PMID- 1514473 TI - Unusual aspects of bacterial water-borne illnesses. AB - Various water-borne bacteria can cause significant illness. Illness most often results from ingestion of contaminated water or seafood, with gastrointestinal entry of pathogens or their byproducts. The skin and soft tissues are also common entry points, either through trauma in or near the water, or by seawater contamination of an existing wound or break in the skin. Clinically significant water-borne illnesses are still rare. However, because humans are increasingly exposed to contaminated water sources through recreation or habitat, the rate of water-borne illnesses can be expected to increase. In patients who present with gastrointestinal illness or infections that do not respond to conventional therapy, water-borne pathogens should be considered in the differential diagnosis. A complete history, with attention to seafood ingestion and exposure to marine or freshwater life-forms, in conjunction with a high index of suspicion (especially in immunocompromised patients), will increase diagnostic accuracy in patients with water-borne illnesses. PMID- 1514474 TI - Sports-related traumatic hyphema. AB - Traumatic hyphema is a common sports-related eye injury that can cause permanent visual loss. Although referral to an ophthalmologist is advised, the primary care physician is often responsible for making the diagnosis and initiating medical care. A careful history should be taken and a physical examination performed, with attention given to possible accompanying ocular injuries. Proper positioning of the patient and placement of a unilateral eye shield are the first steps in management. Therapy is aimed at preventing secondary hemorrhage, elevated intraocular pressure and corneal blood staining. Surgical intervention may be necessary to preserve vision. Prognosis depends on the size of the hyphema, the development of complications and the presence of associated injuries. Protective eye guards have been shown to be very effective in preventing traumatic hyphema. PMID- 1514475 TI - Erythema nodosum. AB - Erythema nodosum represents an inflammatory process in the septa between the subcutaneous fat lobules. The hallmark lesions are exquisitely tender, erythematous nodules that are distributed symmetrically on the extensor surfaces of the lower extremities. Erythema nodosum is considered an immunologic response, and a wide variety of clinically important antigens have been implicated. It may serve as a cutaneous marker for systemic diseases, such as tuberculosis, sarcoidosis, inflammatory bowel disease and lymphoma. The disease is diagnosed by deep elliptical biopsy and pathologic evaluation. The natural history is resolution with treatment of the underlying disorder or spontaneous regression of idiopathic disease. PMID- 1514476 TI - Sclerotherapy for varicose and telangiectatic veins. AB - Varicose veins of the lower extremities are present in approximately 20 percent of adults. They are often symptomatic and may contribute to the development of cutaneous changes of venous insufficiency. Sclerotherapy is a nonsurgical procedure to eradicate varicosities. It can be performed in the office and is more cost-effective than traditional surgical vein stripping, which requires hospitalization and a recuperation period. Sclerotherapy is relatively safe and effective and may be used to treat both varicose veins and telangiectatic "spider" veins of the lower extremities. PMID- 1514477 TI - Identifying and treating patients with panic attacks. AB - Panic disorder occurs in up to 3 percent of the population and can be socially, emotionally and occupationally disabling. A thorough clinical evaluation is crucial to exclude illnesses with similar presentations, particularly acute cardiac, gastrointestinal or neurologic disease. The noradrenergic nervous system is involved in panic attacks. These attacks are described as sudden, unexpected episodes of intense fear or discomfort, usually lasting five to 30 minutes. Appropriate medications include benzodiazepines, tricyclic antidepressants and monoamine oxidase inhibitors. Alprazolam and clonazepam are quickly effective in alleviating panic, but they cause significant symptoms upon discontinuation. The best-studied drug in the treatment of panic disorder is imipramine; like other tricyclic antidepressants, it can cause increased jitteriness early in treatment. Monoamine oxidase inhibitors may be particularly helpful in patients with panic disorder who exhibit social avoidance. Behavior therapy, an important component of treatment, involves the patient's confrontation of fears or phobias. PMID- 1514478 TI - Reporting of adverse drug events: a key to postmarketing drug safety. PMID- 1514479 TI - ACIP issues influenza prevention guidelines. PMID- 1514480 TI - NCI makes changes in the Bethesda System. PMID- 1514481 TI - Thrombolysis-related early patency reduces ECG late potentials after acute myocardial infarction. AB - To assess the effects of thrombolysis and reperfusion on late potentials after myocardial infarction, 101 patients (79 men, age 63.2 +/- 10.5 years) underwent signal-averaged ECG studies at 10.7 +/- 9.2 days, with the use of a 40 to 250 Hz band-pass filter. Patients were divided into four groups: (1) 54 patients treated with thrombolytic agents at 2.8 +/- 1.1 hours, with 81% "early" patency/reperfusion (TIMI grades 2 and 3); (2) 47 patients treated conventionally with 45% "late" patency/reperfusion; (3) 56 patients with patency (TIMI grades 2 and 3); and (4) 26 patients without patency (TIMI grades 0 and 1). A late potential was present when greater than or equal to 2 of 3 defined criteria were present. There was a significant difference in the incidence of late potentials between groups 1 and 2 (22% vs 43%, respectively; p = 0.048) and between groups 3 and 4 (18% vs 50%, respectively; p = 0.006). Late potentials also tended to occur less often after "early" than after "late" patency/reperfusion (12.5% vs 25%). The odds ratio for developing a late potential was 0.39 for thrombolysis versus no thrombolysis (p less than 0.05) and 0.22 for patency/reperfusion (TIMI grades 2 and 3) versus no patency/reperfusion (TIMI grades 0 and 1) (p less than 0.05). By analysis of covariance the effects of thrombolysis on late potentials were entirely explained by reperfusion. Thus the risk of late potentials after myocardial infarction is high but is reduced by thrombolysis and reperfusion. In addition, the effectiveness of "early" reperfusion appears to be greater than that of "late" but requires further clarification. PMID- 1514482 TI - Coronary angioplasty of chronic occlusions: factors predictive of procedural success. AB - In a retrospective study of 365 chronic total occlusions that were submitted for angioplasty, we studied the influence of 27 clinical, morphologic, and procedural variables as possible predictors of successful outcomes. Success rate was shown to be significantly influenced by the following variables: operator experience (41% in early patients, first 6 months; 73% in late patients, last 6 months of entire series; p less than 0.001), duration of occlusion (less than or equal to 1 month, 89%; 1 to 3 months 87%; greater than or equal to 3 months 45%; unknown 60%; p less than 0.001), morphology of occlusion (tapered, 83%; abrupt, 51%), length of occlusion (less than or equal to 15 mm, 71%; greater than 15 mm, 60%; p less than 0.001), and bridging collaterals (present, 29%; absent, 67%; p less than 0.001). None of the other clinical, angiographic, or procedural variables correlated with the success rate of coronary angioplasty. The calculated probability for an experienced operator (greater than 100 occlusions attempted) to successfully open an occlusion with favorable morphology (less than or equal to 1 month old, short, tapered, without bridging collaterals) is 99%. An attempt by the same operator to open an occlusion with unfavorable structure (greater than or equal to 3 months old, long, untapered) has only 47% probability of success. The probability increases to 84% when the occlusion is tapered. We concluded that in addition to the duration and the length of occlusion, tapered morphology, bridging collaterals, and operator experience can predict successful angioplasty in chronic total coronary occlusion. PMID- 1514483 TI - Coronary angioplasty performed with gradual and prolonged inflation using a perfusion balloon catheter: procedural success and restenosis rate. AB - The results of routine coronary angioplasty using gradual and prolonged balloon inflation with a perfusion balloon catheter were evaluated. One hundred forty patients were treated with inflation of the balloon to 6 atm over 3 minutes, with a median inflation time of 15 minutes. The procedural success rate (residual stenosis less than or equal to 50%) was 99%. In-hospital major complications occurred in five patients (3.6%), with one patient experiencing a periprocedural infarction, three patients requiring bypass surgery for abrupt closure, and one patient dying after elective bypass surgery following previous successful angioplasty of a culprit lesion. The restenosis rate in the 117 patients with angiographic follow-up (87% of those eligible) was 42%. Thus gradual and prolonged inflation using a perfusion balloon catheter resulted in a high procedural success rate and a restenosis rate similar to that reported in large studies of patients treated with standard angioplasty. These results warrant further study using a prospective randomized trial design. PMID- 1514484 TI - Endogenous opioid system modulation in anginal pain: demonstration of its central activity. AB - Plasma beta-endorphin levels provide controversial results on the role of endogenous opioid system in modulation of anginal pain. As an alternative, the action of plasmatic luteinizing hormone after administration of naloxone was investigated: naloxone blocks the tonic endogenous opioid system inhibition of gonadotropin release; thus, the level of luteinizing hormone after naloxone administration is an index of central endogenous opioid system activity. Twenty patients with coronary artery disease and positive results of stress tests were selected: 10 had angina (group I) and 10 did not (group II). Ten healthy subjects were also studied as a control group (group III). In all patients basal plasma beta-endorphin levels, basal luteinizing hormone plasma levels (every 15 minutes for 1 hour) and luteinizing hormone plasma levels after administration of 0.1 mg/kg naloxone over 4 minutes (every 15 minutes for 2 hours) were determined. In 15 patients the test was performed after luteinizing hormone releasing hormone was given. The integral concentration time of luteinizing hormone plasma level during baseline (LHiB) and after administration of naloxone (LHiN) or luteinizing hormone releasing hormone (LHiRH), the ratio (LHiN:LHiB and LHiRH:LHiB) and the differences (LHiN-LHiB and LHiRH-LHiB) between the postinfusion period and baseline were calculated. No difference was found in beta-endorphin plasma levels and luteinizing hormone response after luteinizing hormone releasing hormone infusion.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1514485 TI - Effects of sublingually administered nifedipine on left ventricular isovolumic relaxation, diastolic filling, and distensibility in patients with chronic coronary artery disease. AB - The acute effects of nifedipine (20 mg) on left ventricular diastolic function were investigated in 16 patients with chronic coronary artery disease by measuring left ventricular pressure with a manometer-tipped catheter and by measuring volume with cineangiography. Heart rates were maintained by right atrial pacing. Left ventricular peak systolic pressure (-15%; p less than 0.01 vs control) decreased significantly. With afterload reduction, left ventricular ejection fraction (+11%; p less than 0.01) increased. There was no significant change in left ventricular end-diastolic pressure. The diastolic peak filling rate of left ventricular volume significantly increased (+36%; p less than 0.05), whereas the time from end-systole to the peak filling rate remained unchanged. Administration of nifedipine did not improve left ventricular relaxation as assessed by the isovolumic pressure decay. There was also no significant change in the left ventricular diastolic pressure-volume relationship. We conclude that nifedipine improves left ventricular systolic function with afterload reduction but has little or no effect on left ventricular diastolic properties in patients with chronic coronary artery disease. PMID- 1514486 TI - Mode of QT correction for heart rate: implications for the detection of inhomogeneous repolarization after myocardial infarction. AB - In 22 conscious, chronically instrumented dogs, the relationship between R-R interval and QT interval was better explained by linear regression than by nonlinear regression according to Bazett's formula. The correction formula QTL = QT-0.1*(RR-1000), which is based on the assumption of a linear relationship between QT and R-R interval, was then compared with Bazett's formula regarding its capability to detect inhomogeneous repolarization 5 to 7 days after temporary occlusion of the left anterior descending coronary artery. This comparison was performed only in those dogs exhibiting changes in QRS duration of less than 5 msec in response to myocardial infarction (n = 12). In these animals, myocardial infarction resulted in a significant dispersion of repolarization between the left ventricular normal zone and the infarct zone and a shift to the right of strength-interval curves of the infarct zone with respect to the normal zone, indicating local dispersion of refractoriness. As opposed to QTc (Bazett's formula), QTL was significantly (p = 0.04) prolonged after occlusion. Hence the adequacy of QT correction contributes significantly to the detection of inhomogeneous ventricular recovery after acute myocardial infarction. PMID- 1514487 TI - Side effects during adenosine thallium imaging with single-port or double-port infusion protocols. AB - The double-port infusion protocol during adenosine thallium imaging involves the use of two infusion systems, one for adenosine and one for thallium. The single port infusion protocol, on the other hand, uses one infusion system; both adenosine and thallium are injected via a "Y" connection. This study examined the possibility that the single infusion system, by displacing a column of blood filled with adenosine, may be responsible for a greater incidence of side effects. In a parallel study, 140 patients underwent adenosine thallium imaging with the single-port system (group 1) and 140 patients underwent imaging with the double-port system (group 2). Both groups were comparable in age (67 +/- 10 years vs 64 +/- 11 years), gender (men comprised 56% of patients in group 1 and 64% in group 2), resting heart rate, and systolic blood pressure. More patients in group 1 had chest pains (57% vs 44%; p = 0.03), ST-segment depression (25% vs 9%; p = 0.005), nausea (11% vs 4%; p = 0.04), and second- or third-degree atrioventricular block (11% vs 5%; p less than 0.08) than did patients in group 2. The other side effects were similar, and peak heart rate and peak systolic blood pressure were also similar. The thallium images that used single-photon emission computed tomography were abnormal in 61% of patients in group 1 and in 65% of patients in group 2 (p = not significant).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1514488 TI - Safety and diagnostic accuracy of adenosine thallium-201 scintigraphy in patients unable to exercise and those with left bundle branch block. AB - Three hundred forty consecutive patients (mean age 69 +/- 9 years) were evaluated with adenosine tomographic thallium-201 scintigraphy for suspected coronary artery disease. Minor side effects occurred in 91% of patients. Out of 28 patients (8%) with potentially serious side effects, 28 had significant atrioventricular (AV) block (second-degree, 24 patients; third-degree, four patients; syncope occurred in two patients). Acute bronchospasm and severe refractory angina pectoris occurred in one patient each. All side effects were transient and without sequelae. One hundred twenty-one patients underwent coronary angiography within 9 days of adenosine thallium imaging. The predictive accuracies of adenosine thallium imaging for identifying and localizing ischemia to a specific coronary distribution were: left anterior descending = 88%, left circumflex = 84%, right coronary = 88%. The predictive accuracy of adenosine thallium imaging in patients with left bundle branch block was 91%, and was higher than the 71% predictive accuracy noted in 39 patients who underwent exercise thallium testing (p = 0.04). It is concluded that adenosine thallium-201 myocardial scintigraphy was (1) highly accurate for the detection and localization of significant coronary artery disease; (2) it was more accurate at detecting ischemia in patients with left bundle branch block than exercise thallium testing, and (3) subjective side effects were common and were of no diagnostic importance; transient AV block occurred occasionally. PMID- 1514489 TI - Transient ST segment depression during Holter monitoring: how to avoid false positive findings. AB - To increase the specificity of 24-hour Holter monitoring in detecting transient myocardial ischemia, we separated genuine ST deviations from those dependent on artifacts by adding a detailed shape analysis of real-time printouts to the usual criteria of significant ST segment depression. We screened 116 apparently healthy subjects; 31 had to be excluded, because of pathologic findings in preliminary examinations. The remaining 85 (49 women and 36 men; mean age, 43.1 years) underwent Holter monitoring for assessment of the extent, frequency, and duration of episodes of horizontal and descending ST segment depression of at least 0.1 mV that persisted for at least 60 msec after the J point and that were at least 1 minute apart. On the basis of these criteria, six subjects (7.1%) showed 24 episodes of horizontal or descending ST segment depression with a mean of 0.2 mV (range, 0.15 to 0.25 mV), a frequency of four episodes per 24 hours (one to nine), and a duration of 12.2 minutes (range 3-range 41 minutes). Supplementary criteria--e.g., sudden onset of ST segment depression, identical orientation of PQ and ST segments, or simultaneous increase in R and P wave amplitude--made it possible to identify ST changes caused by artifacts in four volunteers. In only two subjects (2.4%) could true silent ischemia not be differentiated from false positive results. Thus consideration of only the extent, frequency, and duration of episodes does not permit a differentiation between true silent ischemia and false positive results. A supplementary shape analysis increases the specificity of ST segment analysis in detecting transient myocardial ischemia during 24-hour Holter monitoring. PMID- 1514490 TI - Adjuvant metoprolol improves efficacy of class I antiarrhythmic drugs in patients with inducible sustained monomorphic ventricular tachycardia. AB - Inducible ventricular tachycardia frequently persists despite solitary class I antiarrhythmic drug therapy. To determine the effect of metoprolol as adjuvant therapy, 19 patients with clinical ventricular tachycardia with baseline inducible sustained monomorphic ventricular tachycardia and persistently inducible ventricular tachycardia despite class I drugs were evaluated. Eight of 19 patients (42%) became noninducible when metoprolol was added to class I drug therapy. Sixteen of 19 patients (84%) were harder to induce or noninducible on a regimen of adjuvant metoprolol therapy. In evaluating the clinical characteristics of the 19 patients, no significant differences were found between patients who were persistently inducible and those rendered noninducible. In evaluating the electrophysiologic characteristics, the group eventually rendered noninducible had a significantly shorter baseline induced cycle length (259 +/- 27 vs 305 +/- 53 msec). Combination class I drug and metoprolol therapy significantly lengthened the ventricular effective refractory period in both groups compared with baseline. The long-term follow-up was excellent in all patients remaining on metoprolol in the noninducible group. Therefore adjuvant metoprolol therapy creates a significant improvement in a number of patients with persistently inducible ventricular tachycardia despite class I drug therapy. PMID- 1514491 TI - Role of mapping-guided surgery in patients with recurrent ventricular tachycardia. AB - To assess the value of ventricular tachycardia (VT) surgery 108 patients with recurrent episodes of VT were studied. There were 97 patients with coronary artery disease (group I) and 11 patients without coronary artery disease (group II). All patients in group I underwent subendocardial resection; 12 patients also underwent cryoablation. Cryoablation alone was performed in all patients in group II. During a mean follow-up period of 40 +/- 27 months, 29 patients (30%) in group I and two patients (18%) in group II died (p = 0.33). There were nine patients (9%) in group I and six patients (55%) in group II who had nonfatal recurrences of VT after surgery (p less than 0.01). In group I, there was a higher mortality rate among patients who had VT of posterolateral origin (14 of 31 patients; 45%) compared with 3 of 11 patients (28%) who had VT of anterolateral origin, 1 of 8 patients (12%) who had VT of inferoseptal, and 11 of 39 (29%) patients who had VT of anteroseptal origin. None of the eight patients with two distinct origins of VT died. PMID- 1514492 TI - A randomized double-blind crossover study comparing the efficacy and tolerability of flecainide and quinidine in the control of patients with symptomatic paroxysmal atrial fibrillation. AB - Patients with paroxysmal atrial fibrillation (PAF) are prone to recurrence. We compared the efficacy and tolerability of flecainide acetate in the control of PAF by means of conventional treatment with quinidine in 19 patients without structural heart disease. A randomized, placebo-controlled, crossover protocol consisting of 8 weeks of treatment with either agent was used. The recurrence of PAF was documented in a symptom diary and confirmed by event ECG recording. Complete control of symptoms was achieved in 4 of 19 and 2 of 11 of patients with flecainide and quinidine, respectively. Both agents prolonged the time to the first recurrence and significantly reduced the total duration of PAF recurrence by 40% and 47%, respectively (p less than 0.05 compared with placebo). Compared with quinidine, flecainide significantly reduced the frequency of recurrence and the rate of PAF during a recurrent episode. However, treatment with flecainide was associated with a higher incidence of symptomatic sinus pauses and visual disturbances compared with a higher incidence of gastrointestinal side effects with quinidine. During a follow-up period of 32 months, satisfactory control was achieved in 74% of patients with the use of these two antiarrhythmic agents. PMID- 1514493 TI - Contractile, metabolic and arrhythmogenic effects of ionic and nonionic contrast agents in the isolated rat heart. AB - Intracoronary administration of contrast agents may be associated with contractile dysfunction and arrhythmias. To further establish the mechanisms of these alterations, we studied high-energy phosphate metabolism, developed pressure, the occurrence of arrhythmias, and the effects of verapamil during infusion of ionic and nonionic agents in isovolumic, retrogradely perfused rat hearts using 31P nuclear magnetic resonance imaging (NMR). Diatrizoate meglumine (Renografin) infusion reduced developed pressure (DP) to 17.1 +/- 3.4% (p less than 0.001) of the control level, and immediately following termination of the infusion, sudden ventricular tachycardia (VT) was observed in four of six hearts. In the presence of verapamil, meglumine reduced DP to 13 +/- 1.9% of control values and none of these six hearts developed VT. Iopamidol infusion in the presence of verapamil (n = 6) and alone (n = 6) resulted in a decrease in DP to 87% of control value, and no arrhythmias, significant change in high-energy phosphate levels, or changes in pH were observed. These results suggest that contrast-induced contractile depression is not mediated by changes in high-energy phosphate metabolism or pH. Arrhythmias associated with meglumine administration alone and suppressed by verapamil are probably related to calcium loading. PMID- 1514494 TI - Influence of mitral valve morphology on mitral balloon commissurotomy: immediate and six-month results from the NHLBI Balloon Valvuloplasty Registry. AB - Echocardiographic data were analyzed in 555 patients undergoing mitral balloon commissurotomy (MBC). Patients were enrolled in the National Heart, Lung, and Blood Institute Balloon Valvuloplasty Registry from 24 centers. There were 456 women and 99 men with a mean age of 54 years. Before MBC the two-dimensional echocardiographic variables of mitral valve thickness, mobility, calcification, and subvalvular disease were evaluated and assigned scores of 1 to 4. The mitral valve morphology score was related to mitral valve area (MVA) measured after MBC by cardiac catheterization. The leaflet mobility score was related to the immediate post-MBC MVA: 2.2 +/- 0.8 cm2 for grade 1, 1.9 +/- 0.7 cm2 for grade 2, 1.7 +/- 0.7 cm2 for grade 3, and 1.9 +/- 0.9 cm2 for grade 4 (p less than 0.001). Results of the MVA after MBC showed a similar relationship for each echocardiographic variable. The total morphology score (sum of the four variables) showed a weak relationship to MVA immediately after MBC (r = 0.24), which was persistent at 6 months after MBC (r = -0.25). Multiple regression analysis showed that the MVA after MBC is predicted by pre-MBC MVA (p less than 0.001), left atrial size (p = 0.01), balloon diameter (p = 0.02), cardiac output (p = 0.004), and leaflet mobility (p = 0.01). The R2 of the model was 0.31 (p less than 0.001). Total morphology score, leaflet thickness, calcification, and subvalvular disease were not important univariate or multivariate predictors of the results of MBC.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1514495 TI - Systolic anterior motion of the chordal apparatus after mitral ring insertion. AB - To describe the Doppler and two-dimensional echocardiographic characteristics of systolic anterior motion of the chordal apparatus after mitral annuloplasty, 24 consecutive patients (19 men and 5 women; mean age, 55 years) were studied with the use of serial Doppler and two-dimensional echocardiography, which included preoperative transthoracic, intraoperative epicardial, and postoperative transthoracic examinations at 1 week after annuloplasty and every 3 months thereafter for up to 12 months. Systolic anterior leaflet motion of the mitral valve was not seen in this series; however, chordal systolic anterior motion was seen in three patients during surgery and in one additional patient at the time of the 1-week transthoracic examination. During subsequent studies at 3-month intervals, chordal systolic anterior motion was not present. The left ventricular outflow tract velocities were normal in all patients with and without chordal systolic anterior motion. In conclusion, chordal systolic anterior motion should be differentiated from leaflet systolic anterior motion after mitral annuloplasty because the former is a transient, benign, and relatively common finding. PMID- 1514496 TI - Mobile strands are frequently attached to the St. Jude Medical mitral valve prosthesis as assessed by two-dimensional transesophageal echocardiography. AB - Two-dimensional transesophageal echocardiographic findings are reported in 13 patients with structurally and functionally normal St. Jude Medical bileaflet mitral valve prostheses. Multiple mobile linear echogenic densities attached to the pivot of the prosthesis were present in 9 of 13 patients. These densities may represent fibrin strands. These mobile strands alternatively resolve and reform over a period of 5 to 14 months after mitral valve replacement. No adverse clinical events were attributable to these prosthetic mitral valve strands. We conclude that mobile stands are frequently attached to the structurally and functionally normal St. Jude Medical mitral valve prosthesis. The clinical significance of these prosthetic mitral valve strands requires clarification. PMID- 1514497 TI - Comparison of cardiac dimensions by transesophageal and transthoracic echocardiography. AB - Transesophageal echocardiography (TEE) has advanced rapidly as a valuable cardiovascular diagnostic technique. As the use of TEE increases, so does the importance of well-defined normal cardiac measurements. Presently, few data exist on the accuracy of M-mode TEE-derived measurements. Therefore in 81 adult patients, TEE-derived M-mode measurements were compared with analogous measurements that were made by standard M-mode transthoracic echocardiography (TTE). The TTE and TEE measurements did not differ in aortic root diameter, end diastolic left ventricular diameter, end-diastolic septal wall versus anterior wall thickness, or end-diastolic posterior wall versus inferior wall thickness. These TEE measurements were within 95% confidence limits of TTE measurements. TEE derived left atrial diameter (3.5 +/- 0.8 cm) was less than that derived by TTE (3.8 +/- 0.8 cm; p less than 0.001) and fell outside of the 95% confidence interval. TTE left atrial size could be estimated as follows: TTE-derived left atrial diameter = TEE-derived left atrial diameter x 0.6 + 1.5 cm. In conclusion, M-mode measurements of aortic root diameter, left ventricular diameter, and wall thicknesses as derived by TTE and TEE are comparable. TEE-derived left atrial diameter may be used to estimate the left atrial TTE measurement. TEE-derived M mode measurements are likely to be most useful when results of TTE are technically inadequate. PMID- 1514498 TI - The influence of obesity on left ventricular filling and systolic function. AB - Little information on the possible influence of obesity on diastolic function is available. Thus we studied 24 asymptomatic obese volunteers (greater than 120% ideal body weight; mean 153 +/- 30%), aged 34 +/- 11 years. Each obese subject was matched for age, height, and sex, with a healthy normal-weight control subject. Isovolumic relaxation time (IVRT) and diastolic filling indexes were determined by pulsed Doppler echocardiography. The IVRT was significantly prolonged in the obese group (84 +/- 17 msec) as compared with the control group (57 +/- 13 msec; p less than 0.0002). Multiple regression analysis showed that percentage of ideal body weight was the most important predictor of peak early filling velocity (r = 0.59, p less than 0.005) and mean deceleration rate of early filling (r = 0.61, p less than 0.005) in the obese group. However, age as compared with percentage of ideal body weight was a more important determinant of the relative distribution of early and atrial filling, such as peak early-to atrial filling velocity ratio (r = -0.75, p less than 0.0001). Ejection fraction, heart rate, and blood pressure did not differ between the obese and control groups. In conclusion, obesity is associated with preclinical abnormalities of IVRT, which may reflect impaired relaxation. The IVRT may be useful in the early detection of left ventricular dysfunction in obesity. Last, studies comparing Doppler indexes of diastolic filling among groups must control for potential differences in percentage of ideal body weight. PMID- 1514499 TI - Ventilatory mechanisms of exercise intolerance in chronic heart failure. AB - Mechanisms that have been suggested to underlie the abnormal ventilatory response to exercise in patients with chronic congestive heart failure (CHF) include high pulmonary pressures, ventilation-perfusion mismatching, early metabolic acidosis, and abnormal respiratory control. To evaluate the role that ventilation and gas exchange play in limiting exercise capacity in patients with CHF, data from 33 patients with CHF and 34 normal subjects of similar age who underwent maximal exercise testing were analyzed. Maximal oxygen uptake was higher among normal subjects (31.7 +/- 6 ml/kg/min) than among patients with CHF (17.7 +/- 4 ml/kg/min; p less than 0.001). The ventilatory equivalent for oxygen, expressed as a percentage of maximal oxygen uptake, was 25% to 35% higher among patients with CHF compared with normal subjects throughout exercise (p less than 0.01). A steeper component effect of ventilation on maximal oxygen uptake was observed among normal subjects compared with patients with CHF, which suggests that a significant portion of ventilation in CHF is wasted. Maximal oxygen uptake was inversely related to the ratio of maximal estimated ventilatory dead space to maximal tidal volume (VD/VT) in both groups (r = -0.73, p less than 0.001). Any given oxygen uptake at high levels of exercise among patients with CHF was accompanied by a higher VD/VT, lower tidal volume, and higher respiratory rate compared with normal subjects (p less than 0.01). Relative hyperventilation in patients with CHF started at the beginning of exercise and was observed both below and above the ventilatory threshold, which suggests that the excess ventilation was not directly related to earlier than normal metabolic acidosis. Thus abnormal ventilatory mechanisms contribute to exercise intolerance in CHF, and excess ventilation is associated with both a higher physiologic dead space and an abnormal breathing pattern. The high dead space is most likely due to ventilation-perfusion mismatching in the lungs, which is related to poor cardiac output, and the abnormal breathing pattern appears to be an effort to reduce the elevated work of breathing that is caused by high pulmonary pressures and poor lung compliance. PMID- 1514500 TI - A comparison of the acute hypotensive effects of two different doses of nifedipine. AB - To determine whether a dose of 5 mg of nifedipine would be useful in the treatment of hypertensive emergencies, we compared the acute hypotensive effects of two different doses of nifedipine, 5 mg and 10 mg, in patients with severe hypertension. In this prospective, randomized, double-blind study, 30 consecutive black patients with diastolic blood pressure that was equal to or greater than 115 mm Hg received either a 5 mg or 10 mg nifedipine capsule and a placebo capsule, which matched that of the alternative strength. Patients were asked to bite the capsules and swallow the contents. Blood pressure response over 4 hours and adverse effects were monitored. Mean systolic blood pressure was reduced from 191.7 mm Hg (95% confidence interval 170.8 to 212.7 mm Hg) to 157.9 mm Hg (137.0 to 178.9 mm Hg) and 206.1 mm Hg (185.1 to 227.0 mm Hg) to 153.7 mm Hg (132.8 to 174.7 mm Hg) in patients who were given 5 mg and 10 mg doses of nifedipine, respectively. Mean diastolic blood pressure in the group of patients that received 5 mg doses of nifedipine decreased from 128.2 mm Hg (115.6 to 140.7 mm Hg) to 105.2 mm Hg (92.7 to 117.7 mm Hg); the corresponding values in the group that received 10 mg doses of nifedipine were 129.9 mm Hg (117.4 to 142.5 mm Hg) and 97.5 mm Hg (85.0 to 110.1 mm Hg), respectively. The minimum mean systolic blood pressures occurred 20 and 25 minutes after administration of the 5 mg and 10 mg capsules, respectively; the minimum diastolic blood pressures were reached after 20 and 30 minutes, respectively.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1514501 TI - Regional blood flow in human congestive heart failure. AB - Despite the total-body consequences of congestive heart failure, little information is available on the distribution of cardiac output and regional-organ hemodynamics in this condition in humans. Technical and methodologic limitations probably account for the paucity of data in this area. Available data indicate that blood flow to the regions or organs studied, namely, the kidneys, hepatosplanchnic region, and upper limbs, decreases in proportion to the reduction in cardiac output. However, renal blood flow appears to be protected in human heart failure by a form of "autoregulation" during marked depression of cardiac output (less than 2.0 L/min/m2). Results of preliminary studies suggest that the regulation of regional-organ hemodynamics is disturbed in this human condition. Cardioactive drugs profoundly affect regional-organ hemodynamics independent of changes in central hemodynamics and cardiac output. The determination of regional blood flow responses in human heart failure will become more important as we expand our knowledge base of the pathophysiology of heart failure, learn more about local vascular control mechanisms, and pursue the potential therapeutic objective of selectively augmenting regional-organ hemodynamics and function. PMID- 1514502 TI - Arterial occlusive disease in occult cancer. AB - Thromboembolism frequently complicates advanced cancer. The incidence of TE as one of the initial manifestations of occult cancer and the diagnostic value of TE as a signal of a possible unrecognized tumor were the subjects of recent studies. TE may precede the diagnosis of cancer by several months or years. The polymorphism of manifestations of paraneoplastic TE has been described previously. An accelerated course of intermittent claudication and of ischemic heart disease has been described in patients with cancer and probably represents additional variants of Trousseau's syndrome. Recently, clues for the presence of occult neoplasms in patients with TE have been proposed. Their value in the stratification of patients needs to be established in prospective studies. That cancer may be responsible for a precipitated course of coronary or peripheral arterial disease raises the question of whether work-up is recommended to uncover a silent malignancy in a patient who has been referred for treatment of these severe ischemic syndromes. PMID- 1514503 TI - The electrocardiographic, clinical, and electrophysiologic spectrum of idiopathic monomorphic ventricular tachycardia. AB - Clinical, ECG, and electrophysiologic data from 47 patients who had episodes of sustained or nonsustained monomorphic VT with no evidence of structural heart disease were reviewed. According to the QRS configuration during tachycardia, four groups were distinguished. Nine patients had a right bundle branch block configuration and superior frontal plane QRS axis (group 1). Nine patients had a right bundle branch block configuration but an intermediate or right QRS axis (group 2). Group 3 consisted of five patients with a left bundle branch block configuration and a left axis deviation, and in group 4 there were 24 patients who had a left bundle branch block configuration with an intermediate or right frontal axis. Patients in group 1 had dizziness during tachycardia less frequently, but they needed cardioversion to terminate their arrhythmias more often. They experienced tachycardia during exercise less often, and tachycardia was not initiated during exercise testing. They had fewer ventricular premature beats according to the Holter recording. During the electrophysiologic study, VT was induced and terminated by pacing more often in this group. Patients with idiopathic VT with a right bundle branch block configuration and a superior axis seem to be a unique group of patients with idiopathic VT, and reentry seems to be the most likely arrhythmia mechanism in this group. The other ECG configurations share the same clinical and electrophysiologic characteristics, which suggest that the underlying arrhythmia mechanism is the same. PMID- 1514504 TI - The use of antibodies in clinical cardiology. AB - Monoclonal antibody technology has resulted in an entirely new class of agents, which have been applied to a variety of problems in cardiology and which hold great promise for future diagnostic, as well as therapeutic, applications. The four antibodies, which have been most widely used in clinical cardiology, are Digibind, OKT3, Myoscint, and 7E3. Each demonstrates the unique potential for the use of antibodies in clinical cardiology. PMID- 1514506 TI - Isolated coronary ostial stenosis in elderly patients: correction by directional coronary atherectomy. PMID- 1514505 TI - Efficacy of lipid profiles in prediction of coronary disease. AB - National guidelines in the United States and Europe have stimulated interest in controlling blood lipid levels to prevent CHD. In this review, the efficiency of lipid profiles in predicting CHD has been examined, and total cholesterol, HDL and LDL cholesterol, and triglyceride values have been compared on the basis of 12 to 14 years of surveillance in the Framingham Study. The average value of total cholesterol and LDL cholesterol in patients who had coronary disease was at or below values that are considered dangerous, which indicates the need for more specific and sensitive lipid profiles. Measurement of LDL cholesterol levels predicted CHD only marginally better than measurement of serum total cholesterol. Measurement of triglyceride levels was the weakest predictor. The total cholesterol to HDL cholesterol ratio was the most efficient predictor both in those with apparently safe and those with abnormal cholesterol values. Measurement of HDL cholesterol was the best single lipid predictor and use of this measurement avoids needlessly alarming or falsely reassuring persons at risk for CHD who have high total cholesterol values. Since the risk associated with any serum cholesterol value varies over a 10-fold range depending on coexistent cardiovascular risk factors, these lipid factors must be taken into account in judging the hazards and efficacy of treatment needed. Evidence is available that controlling elevated cholesterol by diet and administration of pharmaceutical agents can reduce the rate of coronary events, slow progression of angiographically visualized lesions, and regress xanthomata.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1514507 TI - Atrioventricular node reentry that utilizes triple nodal pathways. PMID- 1514508 TI - Catecholamine modulation of sinus node automaticity during complete sinoatrial block: demonstration by direct recording. PMID- 1514509 TI - Transesophageal echocardiography for evaluation of thrombosed mitral valve prosthesis during thrombolytic therapy. PMID- 1514510 TI - Successful use of low-dose tissue plasminogen activator for treatment of thrombosed prosthetic valve in a 22-month-old child. PMID- 1514511 TI - Transesophageal echocardiography in the pregnant patient. PMID- 1514512 TI - Initial presentation of cor triatriatum in a 55-year-old woman. PMID- 1514513 TI - Transesophageal two-dimensional and Doppler echocardiographic diagnosis of cor triatriatum in the adult. PMID- 1514514 TI - Diagnosis of ventricular assist device malfunction by transesophageal echocardiography. PMID- 1514515 TI - Transesophageal echocardiographic diagnosis of coronary sinus orifice atresia. PMID- 1514516 TI - Improved identification of posterior left ventricular pseudoaneurysms by transesophageal echocardiography. PMID- 1514517 TI - Acute tricuspid papillary muscle rupture following blunt chest trauma. PMID- 1514518 TI - Primary pericardial mesothelioma: one-year event-free survival. PMID- 1514519 TI - Absent left pulmonary vein without anomalous connection: diagnosis and management in the newborn. PMID- 1514520 TI - Delineation of obstruction in total anomalous pulmonary venous connection utilizing magnetic resonance imaging. PMID- 1514521 TI - Septal perforator arteries: from angiographic-morphologic characteristics to related revascularization options. PMID- 1514522 TI - Isorhythmic atrioventricular dissociation revisited. PMID- 1514523 TI - Varying charges for comparably effective cancer treatments. PMID- 1514524 TI - Radiotoxicity of 125I-labeled monoclonal antibody 425 against cancer cells containing epidermal growth factor receptor. PMID- 1514525 TI - Serum lactate dehydrogenase in childhood neuroblastoma. A Pediatric Oncology Group recursive partitioning study. AB - On the basis of an extensive recursive partitioning analysis of 668 patients with newly diagnosed neuroblastoma registered on Pediatric Oncology Group (POG) studies between October 1981 and May 1987, four major subsets of patients were created. Important prognostic factors included the patient's stage of disease, age, and level of serum lactate dehydrogenase (LDH). After adjusting for these factors, no other clinical prognostic factors were significant. The implications for protocol design are that (a) fine tuning of current therapy should be sought for the two favorable disease patient subsets, while (b) novel aggressive therapies are needed for the two unfavorable disease patient subsets where the overwhelming majority are dying. This article may serve as a model for others investigating prognostic factors. The data were divided into two subsets: one was used for an exploratory analysis; the other was used to confirm the exploratory findings. Despite spite the large number of statistical tests performed, the likelihood that the findings can be attributed to chance can be dismissed as virtually zero. PMID- 1514526 TI - Total nodal radiation in progressive sarcoidosis. Case report. AB - The subject of this article is a patient with sarcoidosis with neurological involvement, who failed to respond to high dose steroid therapy and cyclophosphamide. Low doses (20 Gy) of total nodal and craniospinal irradiation resulted in an excellent response, the patient being alive and in good health 3 years after irradiation without any further steroid therapy. PMID- 1514527 TI - Etoposide plus carboplatin admixture. Phase I study of five- or seven-day continuous infusion. AB - Thirty-five patients were entered in a Phase I trial of an admixture infusion of etoposide (VP-16) and carboplatin (CBDCA) administered continuously for 5 or 7 days. Because of the compatibility and solubility of the two agents, the treatment program could be administered on an outpatient basis. The dose rate of VP-16 was fixed at 30 mg/m2/day (total dose 150 mg/m2 for 5 days or 210 mg/m2 for seven days) for each cycle. Carboplatin was evaluated at three dose rates: 50, 60, and 75 mg/m2/day on the 5-day infusion and 40, 50, and 60 mg/m2/day on the 7 day infusion with cycles repeated at 28 to 42 days. The dose limiting toxicity was hematologic and followed a pattern typical for carboplatin, that is, delayed neutropenia and/or thrombocytopenia with a protracted leukocyte recovery. Renal toxicity was observed in three patients. The optimum total dose for the infusional carboplatin component was 300 mg/m2 (5-day) and 420 mg/m2 (7-day). The total etoposide dose was 150 mg/M2 and 210 mg/M2, which did not appear to contribute to the hematologic toxicity. Delivery of the admixture of VP-16 and CBDCA was feasible, although cumbersome, as a result of the portable delivery system. Extending the duration of infusion increases the total cumulative dose of carboplatin and etoposide that can be administered without increasing adverse effects. PMID- 1514528 TI - Deferoxamine, cyclophosphamide, etoposide, carboplatin, and thiotepa (D-CECaT): a new cytoreductive chelation-chemotherapy regimen in patients with advanced neuroblastoma. AB - Thirteen patients with Stage III (3 patients) or Stage IV (10 patients) neuroblastoma were treated with a new iron chelation-cytotoxic therapy regimen. Deferoxamine given for five consecutive days followed by 3 days of cyclophosphamide, etoposide, carboplatin, and thiotepa (D-CECaT) caused moderate to severe myelotoxicity. In 39 courses there were four episodes of sepsis; platelet and packed red blood cell transfusions were required in 72% and 82% of courses, respectively. Mild nausea and vomiting occurred in 52% of courses. Objective responses after two courses were observed in 12 of 13 patients. Three of four partial responses were achieved in previously treated relapsed patients, and seven of eight complete responses (four of which were surgically documented) were achieved in previously untreated patients. This cytoreduction regimen appears to be an improvement over other initial induction regimens and may be worth testing in larger populations. PMID- 1514529 TI - Intraoperative radiation therapy of extrahepatic biliary carcinoma: a report of RTOG-8506. AB - Twenty-three patients with unresected, resected but residual, or locally recurrent biliary duct cancer were entered on a Radiation Therapy Oncology Group (RTOG) Phase I-II study. Of 16 patients who were properly entered and eligible for study, eight patients (50%) completed protocol treatment including intraoperative radiation therapy (IORT). Minor acute complications from therapy were common. There was no early grade 3 or 4 toxicity. Major long-term toxicity (grade 4) was noted in one patient who suffered a perforated viscous related to salvage radiation therapy for a scar recurrence and died of infection 1 month after retreatment. With a median follow up of 10.5 months, two of the eight patients who received IORT are alive. Of the six patients who died, one had persistent disease, one had the tumor recur in the surgical wound and subsequently died of complications related to retreatment with high dose radiation, and one died of intercurrent disease. In addition, two patients died with liver metastasis, and one died with intraabdominal disease outside of the IORT volume. Bulk of disease may be an important determinant of outcome. PMID- 1514530 TI - A phase I-II study of recombinant intrapleural alpha interferon in malignant pleural effusions. AB - Malignant pleural effusion is a common and significant source of morbidity for many patients with cancer. In an attempt to control this condition without using chest tube drainage, we administered recombinant interferon alpha-2b (INTRON, Schering-Plough, Kenilworth, NJ) intrapleurally via catheter after routine thoracentesis. Twenty-two installations of interferon were administered to 15 patients in incremental dosages of 3-50 x 10(6) U/m2. Of 20 evaluable treatments, six (30%) achieved effusion stabilization; there were no complete or partial responses. Only one of nine treatments at a dosage less than 20 x 10(6) units/m2 resulted in symptoms, while four of 11 treatments at the higher dosage were associated with transient fever, chills, and chest pain. Interferon demonstrated no major activity in this heavily treated patient population with advanced malignancy. PMID- 1514531 TI - Salvage carboplatin therapy for advanced ovarian cancer after first-line treatment with cisplatin. AB - From April 1989 to August 1990, 17 patients with Stage 3 or 4 epithelial ovarian cancer (EOC) were treated with intravenous carboplatin (160-400 mg/m2) for refractory or recurrent disease after first-line treatment with cisplatin-based combination chemotherapy. Of fifteen patients evaluable for activity, two complete responses and two partial responses were seen, for a response rate of 27%. The duration of response was 4.5, 5, 8, and 9.2 months, respectively, and responders survived longer than nonresponders. Of the nine evaluable patients receiving carboplatin as the first salvage treatment, four responses were seen. Dose selection for the first cycle of carboplatin was based on previous treatment, and adjustments were made on the basis of myelosuppression. In general, treatment was well tolerated--severe myelosuppression occurred after 6 of 73 cycles. This review confirms previous reports of anti-tumor activity of carboplatin in patients with refractory or recurrent advanced EOC who respond to first-line treatment with cisplatin. Further evaluation may help define the toxicity and efficacy of salvage treatment with carboplatin compared to cisplatin in patients who recur after a prolonged disease-free interval after first-line cisplatin-based therapy. PMID- 1514532 TI - Effect of calcium replacement on the hemodynamic changes associated with high dose interleukin-2 therapy. AB - Administration of high-dose IL-2 results in hemodynamic changes that are similar to those seen in septic shock. These include a decrease in systemic vascular resistance (SVR) with a resultant drop in mean arterial pressure (MAP). Hypocalcemia is seen in septic shock and with IL-2 administration. Calcium replacement in septic shock has been reported to result in hemodynamic improvement; we therefore administered calcium to patients receiving high dose IL 2 to correct ionized hypocalcemia. Five consecutive patients underwent invasive hemodynamic monitoring before and during IL-2 administration. Calcium chloride was administered to correct ionized hypocalcemia, and hemodynamic parameters were monitored before and after calcium administration. Ionized hypocalcemia was associated with an elevation in parathyroid hormone levels. There was no toxicity related to the administration of calcium. An improvement in the MAP and SVR was seen early and late (after a dose of IL-2 was held) in the IL-2 treatment cycle; there were minimal effects at other points. Because of the potential hemodynamic benefit of calcium replacement, we recommend that ionized hypocalcemia be corrected in patients receiving high-dose IL-2. PMID- 1514533 TI - Intravenous and oral magnesium supplementations in the prophylaxis of cisplatin induced hypomagnesemia. Results of a controlled trial. AB - The effects of oral and intravenous magnesium supplementation on cisplatin (CDDP) induced hypomagnesemia were investigated in 41 patients treated with 100 mg/m2 CDDP. Patients were randomly allocated to receive no magnesium supplementation, intravenous magnesium supplementation (magnesium sulphate, 3 g before each CDDD administration) or oral magnesium supplementation (magnesium pidolate, 2 g orally every 8 hours on days 2 to 21 of each CDDP course) during the first 4 courses of CDDP treatment. Patients in both supplementation arms showed significantly higher magnesium levels than control patients from the second course on (oral magnesium arm) or from the third course on (intravenous magnesium arm). Three of the 9 patients (33%) in the intravenous magnesium arm and 4 of the 9 (44%) in the oral magnesium arm developed hypomagnesemia after the fourth course of CDDP, compared with 9 of the 10 (90%) unsupplemented patients. There were no magnesium-related side effects in patients on intravenous magnesium supplementation. Two patients treated with oral magnesium developed mild gastrointestinal symptoms (emesis and diarrhea), probably from magnesium therapy. Our study showed that both intravenous and oral magnesium supplementations appear to be safe and efficacious in the prevention of CDDP-induced hypomagnesemia. Since patients were not completely protected, and since the analysis was limited to the first four courses of chemotherapy, additional studies are needed to determine the best schedule of magnesium supplementation, especially in patients who receive more than four courses of CDDP chemotherapy. PMID- 1514534 TI - Superior vena cava obstruction in a patient with chronic lymphocytic leukemia and lung cancer. AB - A patient with cervical lymphadenopathy secondary to chronic lymphocytic leukemia (CLL) developed acute superior vena cava (SVC) obstruction. Poor response to chemotherapy, a history of smoking, and lobar atelectasis suggested a different diagnosis. Bronchoscopy established the presence of a bronchogenic adenocarcinoma of the right lung as the etiology of the obstruction. Based on our experience and a review of the literature, we recommend that if a patient with CLL or a diffuse well-differentiated lymphocytic lymphoma presents with or develops SVC obstruction, additional invasive diagnostic tests must be initiated to exclude the possibility of a coexistent second malignancy or a transformation to a higher grade lymphoma. Other features warranting a search for another diagnosis are lack of the expected response to glucocorticoids, chemotherapy, or radiation therapy. PMID- 1514535 TI - The increasing recognition of adenosquamous lung carcinoma (1977-1986). AB - A retrospective analysis of the data in the tumor registry on all 103 patients with adenosquamous lung carcinoma diagnosed and treated at our center between 1977 and 1986 was performed. The history of tobacco use was available for 100 patients (72 men and 28 women). Ninety-four percent of the patients (100% of men and 79% of women) were smokers, suggesting that adenosquamous carcinoma may be a Kreyberg I type of lung carcinoma. The gender, race, and age distributions in adenosquamous carcinoma were similar to other histologic subtypes of lung carcinoma. Patients less than 45 years old constituted 10%; 45-54 years old, 24%; 55-64 years old, 34%; 65-74 years old, 25%; and greater than 75 years, 7%. In the 95 patients whose stage at the time of diagnosis was known, 11% had local stage; 28%, regional; and 61%, distant stage. The 1-, 2- and 5-year survival of the 103 patients were 27%, 18%, and 8%, respectively. Survival was related to stage. Local stage had the best survival, and greater than 50% of patients were alive at 4 years. Regional stage had an intermediate median survival of 10 months but no survivors at 5 years. Distant stage had the worst median survival (5 months), and one patient (2%) was alive at 3 years. There was a significant increase (two- to three-fold) in the frequency of adenosquamous carcinoma over the 10-year study period, 1977-1986. PMID- 1514536 TI - Metastatic lobular breast carcinoma simulating primary colon cancer. PMID- 1514537 TI - Endotracheal tube position in neonates. PMID- 1514538 TI - Infection with the hepatitis A virus associated with ascites in children. PMID- 1514539 TI - Finger injuries involving stationary exercise bicycles. AB - Injuries to children related to exercise bicycles can result in significant morbidity, but are almost entirely preventable. To forestall these injuries, manufacturers should continue to focus their attention on improved design and developing safer equipment. In addition, pediatricians and other primary care providers need to play a role in educating parents and the community about the possible hazards that exercise bicycles present to young children. PMID- 1514540 TI - Influenza vaccination and acute otitis media in children. PMID- 1514541 TI - Chronic proctitis due to Entamoeba histolytica. PMID- 1514542 TI - Treatment of visceral leishmaniasis. PMID- 1514543 TI - Asymmetric septal hypertrophy in infants of diabetic mothers. PMID- 1514544 TI - Radiology in the dark. PMID- 1514545 TI - The role of maternal autoimmune thyroid disease in neonatal hypothyroidism. PMID- 1514546 TI - Immunization practices of Washington State pediatricians--1989. AB - Administration of immunizations has become complicated by issues about consent, cost, and liability. To determine if these issues have changed the immunization practices of pediatricians, we surveyed pediatricians in private practice in Washington State. The survey results show that about one half of vaccines administered in pediatricians' offices are provided by the Washington State Health Department. The mean charge for administration of each parenteral vaccine was $7.02. Respondents strongly agreed that they would administer vaccine supplied by the Washington State Health Department if it was available. They also agreed that they referred patients to Health Department clinics for vaccination because of inability to pay and not because of concern about liability. PMID- 1514547 TI - Acute-phase reactants and acute bacterial otitis media. AB - OBJECTIVE: To determine if the erythrocyte sedimentation rate and C-reactive protein level are elevated in uncomplicated acute bacterial otitis media. DESIGN: Investigator-blinded, antibiotic efficacy trial. SETTING: The emergency department of an urban regional children's hospital with 24,000 annual visits. PARTICIPANTS: Thirty-one children with symptoms of acute bacterial otitis media of 7 days' duration or less. SELECTION PROCEDURE: Volunteer sample. INTERVENTIONS: Tympanocentesis, oral antibiotics for 10 days, and three follow-up visits in the next 30 days. MEASUREMENTS/RESULTS: The erythrocyte sedimentation rate and C-reactive protein level were obtained at time of entry into the antibiotic study. Seventeen patients (55%; 95% confidence interval, 37% to 72%) had either an erythrocyte sedimentation rate above 20 mm/h or a C-reactive protein level above 8 mg/L. Eleven patients (35%) had a recurrent episode of acute bacterial otitis media during the follow-up period. The relative risk of recurrence of otitis media given an elevated erythrocyte sedimentation rate or C reactive protein level was 8.24 (95% confidence interval, 1.20 to 56.74; Fisher's Exact Test; P = .007). CONCLUSIONS: Clinicians who use elevated acute-phase reactants as possible indicators of invasive bacterial infections should be aware that an elevated erythrocyte sedimentation rate or C-reactive protein level is also consistent with acute bacterial otitis media. An elevated erythrocyte sedimentation rate or C-reactive protein level also appears to be associated with an increased risk of recurrence of acute bacterial otitis media. If these findings can be confirmed in a larger study, the erythrocyte sedimentation rate or C-reactive protein level could be used to assess the risk of recurrent otitis media. PMID- 1514548 TI - Severe laryngotracheobronchitis complicating measles. AB - OBJECTIVE: To determine the incidence of severe measles-related laryngotracheobronchitis in patients hospitalized during a recent measles epidemic and to evaluate factors associated with severity of airway injury and its management. DESIGN: Clinical description of patient series. SETTING: Children's hospital and county general hospital, Houston, Tex. PATIENTS: One hundred twenty-four children (aged 1 month to 19 years) admitted with a diagnosis of measles. INTERVENTIONS: None. MEASUREMENTS/RESULTS: Twenty-seven patients had significant laryngotracheobronchitis, including 10 who had not received appropriate immunization. Six patients required endotracheal intubation for relief of upper airway obstruction. The median age of patients requiring intubation was 12 months (range, 4 to 24 months). Two patients died of complications of superinfection. Two patients survived but required prolonged intubation. Two patients underwent early diagnostic laryngoscopy and bronchoscopy and required shorter artificial airway maintenance. CONCLUSIONS: Severe laryngotracheobronchitis frequently occurs in patients younger than 2 years hospitalized with measles and may be related to bacterial or viral super infection. Early diagnostic laryngoscopy and bronchoscopy for injury assessment and possible endotracheal tube exchange are recommended and, in some severe cases, tracheostomy should be considered to shorten artificial airway maintenance and decrease the incidence of airway complications. PMID- 1514549 TI - Care of the pediatric organ donor. AB - Solid organ transplantation has become an accepted therapeutic option in pediatrics. Many previously fatal diseases have become current indications for organ transplantation. A major limitation to the growth of this therapeutic option is the availability of suitable organs. With organ supply falling far short of demand, recruitment of donors has been stressed. In addition to recruiting donors, physicians are responsible for maintaining optimal organ function in a beating heart organ donor to ensure that all organs that could potentially be harvested are in a condition suitable for transplant. Current information demonstrates numerous physiologic changes resulting from cerebral death. Therapeutic interventions must focus on maintenance of function in all potentially transplantable organs, including kidneys, heart, lungs, liver, and pancreas. Physicians should recognize the interventions that might compromise the use of an organ in transplant. Criteria for organ use are constantly changing, and the implications of different therapeutic interventions must still be evaluated. PMID- 1514550 TI - The role of assisted ventilation in survival after respiratory failure in children with AIDS. AB - OBJECTIVES: To determine the role of assisted ventilation in children with the acquired immunodeficiency syndrome and acute respiratory failure, and to identify any measurement or variable that predicted survival. DESIGN: Retrospective study. SETTING: Kings County (New York) Hospital Center, a tertiary-level inner-city municipal hospital. PARTICIPANTS: Twenty-three children with acquired immunodeficiency syndrome who were endotracheally intubated and mechanically ventilated because of acute respiratory failure. MEASUREMENTS/MAIN RESULTS: There were 24 episodes of acute respiratory failure, as one patient survived a first episode and died during the second episode 2 years later. We failed to identify any measurement or variable that predicted survival. During 12 episodes (50%), the patients survived and were weaned from the ventilator. CONCLUSIONS: Our findings indicate that a decision to avoid intubation and assisted ventilation in a child with acquired immunodeficiency syndrome and acute respiratory failure should not be made based merely on the presumption of a lethal outcome. PMID- 1514551 TI - Experience with flexible fiberoptic bronchoscopy with bronchoalveolar lavage as a diagnostic tool in children with AIDS. AB - OBJECTIVE: To report our experience with flexible fiberoptic bronchoscopy with bronchoalveolar lavage in children with the acquired immunodeficiency syndrome and acute lower respiratory tract disease. DESIGN: Retrospective study. SETTING: Children's Medical Center of Brooklyn, NY, a tertiary-level inner-city hospital. PARTICIPANTS: Eighty-five children with acquired immunodeficiency syndrome and acute lower respiratory tract disease. INTERVENTION: One hundred five flexible fiberoptic bronchoscopies with bronchoalveolar lavages. MEASUREMENTS/MAIN RESULTS: Infective agents were recovered in 88 procedures (84%). Potentially pathogenic bacteria were identified in 56 (56.6%) of 99 procedures. Viruses were found in 28 (29%) of 96 lavages, and fungi in 37 (41.6%) of 89 specimens. Pneumocystis carinii was identified in 22 (22.2%) of 99 specimens. Mycobacteria were isolated from 14 (14%) of 100 specimens. A serious complication occurred in only one procedure (0.95%). CONCLUSION: Flexible fiberoptic bronchoscopy with bronchoalveolar lavage is a safe and effective diagnostic procedure that identified infective agents in 80% of children with acquired immunodeficiency syndrome and concomitant acute lower respiratory tract disease. PMID- 1514552 TI - Superior vena cava syndrome associated with lymphoma. AB - OBJECTIVE: To evaluate the workup and treatment of children with lymphoma and superior vena cava syndrome. DESIGN: A retrospective survey. SETTING: State hospital serving as a secondary and tertiary referral center for pediatric oncology and pediatric cardiac surgery. PARTICIPANTS: Eleven children aged 11 months to 12 years diagnosed as having lymphoma or T-cell acute lymphoblastic leukemia who presented with superior vena cava syndrome during an 11-year period. INTERVENTIONS: Lymph node biopsy (two patients), thoracenthesis (five patients), bone marrow aspiration (two patients), and thoracenthesis in addition to bone marrow aspiration (two patients). All aspirates were evaluated with immunohistochemical studies. Chemotherapy was the only management intervention. RESULTS: T-cell lymphoma or leukemia accounted for nine cases and Hodgkin's disease for two cases. Respiratory symptoms occurred in 10 patients, including tracheal compression in six patients (compression was life-threatening in one patient). Diagnosis of superior vena cava syndrome was achieved in eight patients using surface-marker analysis of aspirates. The syndrome disappeared within 2 to 10 days. Seven of nine children whose conditions were diagnosed more than 1 year before this writing were alive and free of disease after mean follow-up of 37 months. CONCLUSIONS: (1) A specific diagnosis can be achieved in most children with superior vena cava syndrome and lymphoma; (2) Thoracic computed tomographic scans are essential, identifying minute pleural effusions that can aid diagnosis; (3) Anesthetic hazard is related only to severe tracheal compression; (4) Chemotherapy achieves excellent symptomatic relief; and (5) Long-term survival, without disease, is achievable. PMID- 1514553 TI - Home visits by pediatric residents. A valuable educational tool. AB - OBJECTIVE: To establish how many pediatric residency programs offer home visits, to assess the feasibility of making home visits as part of pediatric training, and to determine whether residents perceive home visits as worthwhile learning experiences. DESIGN: A questionnaire was mailed to all medical school pediatric departments in the United States and Puerto Rico to determine the prevalence of home visits during residency training. To study the feasibility of residents making home visits, a pilot program was instituted. PARTICIPANTS: Fourteen pediatric residents participated in the study. Each resident visited a house, trailer, apartment, or shelter for the homeless that was within a 20-minute radius from the medical center. To determine the educational value of home visits, each resident wrote a one-page report immediately on his or her return to the hospital. After about 6 months, all participating residents completed a questionnaire retrospectively evaluating their home visits. SELECTION PROCEDURES: Interns who were neither on-call nor postcall the day of the visits were invited to participate. Patients were selected because they were homebound (eg, ventilator-dependent), had missed follow-up appointments, or had transportation difficulties. RESULTS: Thirteen percent of the pediatric residency programs surveyed currently include home visits. In all 14 of the pilot visits, the home was located without difficulty and the patient was at home. In each case, the family welcomed the visit. All the pediatric residents believed that the home visit was a worthwhile learning experience. CONCLUSIONS: Although very few programs (13%) currently offer home visits as part of pediatric residency training, such visits are feasible within a large urban area. Residents are enthusiastic about seeing how and where their patients live, and consider home visits a worthwhile learning experience. PMID- 1514554 TI - Anaerobic endurance and peak muscle power in children with spastic cerebral palsy. AB - The aim of this study was to provide information on anaerobic muscle endurance (mean power) and peak muscle power in children with spastic cerebral palsy. We measured peak power and mean power of the upper and lower limbs in 29 boys and 20 girls, aged from 6 to 14 years, by means of the Wingate Anaerobic Test. In addition, the physical components (physical capacity, upper limb, and lower limb) of a system used for evaluating function in the physically disabled were assessed. Of the 49 subjects, 46 and 37 successfully completed the arm and leg Wingate Anaerobic Test, respectively. Compared with norms for age and gender (healthy, nonathletic children), peak and mean power in the patients, even when corrected for body weight, were distinctly subnormal. The performance of subjects with quadriplegia was 3 to 4 SDs below the mean for controls. Twenty-five of diplegic and hemiplegic subjects had values below 2 SDs. When the data were analyzed according to the severity of the cerebral palsy, with the use of the physical capacity, upper limb, and lower limb score, those children with moderate to severe cerebral palsy had values for mean and peak power of the arm and leg 3 to 4 SDs below the normal mean. Values for children with only mild cerebral palsy also fell below the mean, but the data were more scattered, especially for the leg. The lower muscle performance may reflect both quantitative and qualitative differences in the upper- and lower-limb muscles, due to altered innervation and, in the more severely affected children, disuse. PMID- 1514555 TI - Calories count. Improved weight gain with dietary intervention in congenital heart disease. AB - OBJECTIVES: We assessed the nutritional status of patients with congenital heart disease (CHD) to evaluate the role of dietary intake in impaired weight for patient length. Underweight patients with CHD underwent nutritional counseling to evaluate the role of this intervention in improvement of weight for length. RESEARCH DESIGN: We prospectively evaluated a clinical protocol for nutritional assessment and counseling in patients with CHD. Eligible patients were enrolled from a cardiology clinic during a 13-month period. Initial anthropometric measurements and measurements of dietary intake of underweight and normal-weight patients were compared. Initial and follow-up measurements of underweight patients who received nutritional counseling were compared. PATIENTS: Nineteen underweight patients with CHD and 16 normal-weight patients with CHD, aged 1 month to 2 years, were studied. Exclusion criteria included noncardiac factors that could affect growth (eg, low birth weight, Down syndrome, gastrointestinal deficit, and any severe abnormality of the central nervous system). Seventeen of the 19 underweight patients underwent nutritional counseling in the presence of a parent every 2 months for 6 months. Caloric and protein intakes were maximized using high-calorie formulas. MEASUREMENTS AND RESULTS: Baseline dietary intake was lower in underweight patients than in normal-weight patients (mean percentage of the recommended daily allowance of calories, 89% vs 108%). Follow-up evaluation in normal-weight patients showed no change in percentage of ideal body weight for length. Follow-up evaluation in underweight patients showed improvement in mean dietary intake (from 90% to 104% of the recommended daily allowance of calories) and in mean percentage of ideal body weight for length after intervention (from 83.1% to 88.3%). CONCLUSION: Nutritional evaluation of patients with CHD demonstrated that underweight children had inadequate diets. Underweight patients with CHD who received nutritional counseling showed increased dietary intake and improved anthropometric measurements on follow-up. PMID- 1514556 TI - Removing meconium from infant tracheae. What works best? AB - OBJECTIVE: At least nine mechanical devices are available for suctioning the tracheae of meconium-stained newborns. To our knowledge, the efficacy of these devices, as well as various suction pressures and patterns, has not been previously compared. We performed this investigation to assess these variables. DESIGN: Fourteen suction techniques (combinations of device, suction pressure, and suction intermittency) were evaluated sequentially in the trachea of each of 14 in vitro newborn piglets (1 to 4 days old); the order was randomized using a Latin square design. We chose three devices to compare: a meconium aspirator (Neotech Products Inc, Chatsworth, Calif), a hand pump (Res-Q-Vac, Repromed Systems Inc, New York, NY), and a 10F suction catheter (Superior Healthcare Group Inc, Cumberland, RI). Both the meconium aspirator and the hand pump were used with a 3.0-mm endotracheal tube. INTERVENTION: We instilled 0.8 mL of a homogeneous mixture of human meconium and saline (44 g of meconium per 100 mL of saline) in the trachea before applying each suction technique. The meconium aspirator and the suction catheter were each evaluated at three different vacuum pressures, -40, -80, and -150 mm Hg, using both continuous and interrupted suction. The hand pump was evaluated with one and two activations (one activation generates -100 cm H2O, according to the manufacturer). MEASUREMENTS AND RESULTS: The percentage of instilled meconium recovered was consistently greatest (P less than .001) with the meconium aspirator (mean, 88.9% at -150 mm Hg, 84.9% at -80 mm Hg, and 73.5% at -40 mm Hg), intermediate with the catheter (mean, 81.0% at 150 mm Hg, 73.2% at -80 mm Hg, and 67.5% at -40 mm Hg), and least for the hand pump (mean, 67.9% with one activation and 72.6% with two activations). Recovery was better with continuous suction (P = .02) and increasing pressure (P less than .001). CONCLUSIONS: Among the techniques compared, the meconium aspirator at -150 mm Hg, using continuous suction, performed best in this model. It is unknown, however, to what extent the tracheal mucosa may be affected by this degree of negative pressure. PMID- 1514557 TI - Radiological cases of the month. Paragonimiasis. PMID- 1514558 TI - Picture of the month. Pigmented lesions of the skin. PMID- 1514559 TI - Pathological case of the month. May-Hegglin anomaly. PMID- 1514560 TI - The development of thyroid storm in a child with McCune-Albright syndrome after orthopedic surgery. AB - OBJECTIVE: To report a case of thyroid storm that developed in a child with McCune-Albright syndrome after orthopedic surgery. The development of thyroid storm has not previously been described after surgery in a child. DESIGN: Descriptive case report. SETTING: Pediatric intensive care unit. PARTICIPANT: Patient with McCune-Albright syndrome who developed thyroid storm. SELECTION PROCEDURES AND INTERVENTIONS: Clinical features and treatment of thyroid storm are described. A highly sensitive immunochemiluminometric thyroid-stimulating hormone assay to help diagnose hyperthyroid states is also described. CONCLUSIONS: Before all operative procedures, children at high risk for thyroid dysfunction, including patients with McCune-Albright syndrome, should be screened and observed closely for the development of thyroid storm. PMID- 1514561 TI - The pediatrician as expert witness. Participation and reaction to this activity. AB - Little is known about the qualifications and motives of pediatricians who provide expert witness testimony. Pediatricians in Pennsylvania were surveyed anonymously to learn more about this practice. Two hundred fifty-five (49%) of 520 pediatricians responded, and 126 of these physicians had provided expert testimony at some time. Fully affiliated medical school faculty members were more likely to act as expert witnesses than were other pediatricians. Seventy-seven (61%) did so to defend a fellow physician. Only eight (6%) were listed with an organization that provides expert witnesses. Pediatricians were selective about their involvement as expert witnesses, and 96 (76%) had refused to give testimony at some time. Most were paid an hourly rate, which was in keeping with charges for medical consultation or lecturing. More than 80% of respondents were unhappy with the present system of procuring expert witnesses. PMID- 1514562 TI - Twinning and neurologic morbidity. AB - OBJECTIVE: To review the literature regarding neurologic morbidity among twins. RESEARCH DESIGN: Review of medical literature and data from the National Center for Health Statistics. CONCLUSIONS: The twinning rate is increasing concurrent with an increase in the survival of twins. Because twins are more often born prematurely and are of low birth weight, and premature infants are at increased risk for neurologic morbidity, twins are vulnerable to this problem. In addition, twins are more likely to develop brain abnormalities in utero, which is thought to be related to placental vascular anastomoses. Pediatricians should expect more twins in the future with congenital neurologic illness. PMID- 1514563 TI - Reliability and construct validity of the Clinical Observations of Motor and Postural Skills. AB - The Clinical Observations of Motor and Postural Skills (COMPS) is a screening tool for children with motor incoordination. A study of reliability (test-retest, interrater, and internal consistency) and construct validity with 132 children, both with and without developmental coordination disorder, is reported here. Test retest reliability over 2 weeks was high: .92 for a group of 48 children. Interrater reliability for occupational therapists experienced in pediatrics was also excellent: .87 for a group of 72 children. Internal consistency of the COMPS was high, particularly when one of the seven items (Schilder's arm extension) was deleted. The test discriminates well between children with and without motor problems and has many properties of a good screening test. PMID- 1514564 TI - Effects of aging on adult hand function. AB - The effects that normal aging have on adult hand function and functional performance are not well understood. An empirical study was conducted examining relationships between prehension pattern type and frequency, hand strength, and performance time in functional tasks. Four groups of 10 adults were selected by age and gender, ranging from 24 to 87 years. Subjects were asked to pour milk into a cup and remove money from a wallet while being videotaped. Prehension patterns were identified with a functionally based classification system. Grip and three types of pinch were measured with a dynamometer and a pinch gauge. Prehension pattern selection did not seem to differ with age. Statistically significant differences in age were found for prehension pattern frequency, hand strength, and performance time. Nondysfunctional older subjects were observed resetting identical prehension patterns secondary to lateral pinch weakness, which contributed to increased prehension pattern frequency and performance time. Hand function seemed to remain stable until age 65 years, after which it diminished slowly. After age 75 years, age differences in performance were most apparent. PMID- 1514565 TI - Performance of preschoolers on the Pediatric Clinical Test of Sensory Interaction for Balance. AB - The purposes of this study were to describe the performance of 40 children aged 4 and 5 years on the Pediatric Clinical Test of Sensory Interaction for Balance (P CTSIB) and to determine whether age- and gender-related differences were present. The P-CTSIB measures standing balance when sensory input is systematically altered. Kruskal-Wallis one-way analyses of variance by ranks (p less than or equal to .05) were used for comparisons by age and gender. When the 4-year-olds were compared with the 5-year-olds, significant duration differences were found in 4 of the 6 conditions in the heel-toe position of the P-CTSIB. The age-related differences on the remaining 2 heel-toe conditions, as well as on Condition 6 of the feet-together position, approached significance. Gender differences with 4 year-olds and 5-year-olds combined were statistically non-significant in all instances; however, girls performed better on 9 of the 12 conditions of the P CTSIB. The results indicate that the feet-together position can discriminate between children without balance deficits and children with balance deficits. The heel-toe position is difficult for children aged 4 and 5 years without balance deficits and consequently has limited diagnostic value for this age group. PMID- 1514566 TI - Dementia management: an occupational therapy home-based intervention for caregivers. AB - This paper describes an occupational therapy intervention designed for family caregivers of persons with dementia. The intervention, based on the framework of a competence-environmental press model and the principle of collaboration, was implemented during 5 home visits. Each visit was designed to build caregiving skills through collaboration in identifying problem areas, developing and implementing environmental strategies, and modifying management approaches. A case vignette illustrates the therapeutic process and outcomes. The theoretical rationale and structure of the intervention and innovative documentation for evaluation of the theoretic process are also presented. PMID- 1514567 TI - Test-retest reliability study of the Pennsylvania Bi-Manual Worksample. AB - Test-retest reliability of a vocational assessment battery called the Pennsylvania Bi-Manual Worksample (PBWS) (Roberts, 1969) was examined in this study. The PBWS was administered to 30 adults with developmental disabilities at two different times, with an interval of 7 to 10 days between administrations. The subjects, who had mild to moderate degrees of mental retardation and ranged in age from 25 to 51 years, were chosen randomly from a group of 95 employees of a sheltered workshop for adults with developmental disabilities in western New York. When the scores from the two test administrations were compared to determine test-retest reliability, a high intraclass correlation value of .98 was found, which indicates that the PBWS provides consistent information about the vocational skills of adults with developmental disabilities. PMID- 1514568 TI - Assessment of codependency behavior in two health student groups. AB - The present study examines the relationship between codependency and caregiving to determine whether codependent persons tend to be attracted to caregiving professions. The study also examined the relationship between codependency, self esteem, and locus of control, as measured by the Friel Co-Dependency Assessment Inventory (Friel, 1985; Friel & Friel, 1987), the Tennessee Self-Concept Scale (Fitts, 1965), and the Internal-External Locus of Control Scale (Rotter, 1966), respectively. Voluntary participants consisted of 15 occupational therapy students and 15 health information administration (HIA) students believed to be different from one another with respect to the caregiving aspects of their respective professions. The occupational therapy group scored significantly lower than the HIA group on the measure of codependency (m = 21.2 vs. m = 28.8, respectively) [t(28) = 2.258, p = 05]. No other significant differences were noted between groups for the other test scores. Only codependency scores between 31 and 60, that is, moderate-to-severe and severe concerns (n = 6), had a strong correlation with self-esteem scores (r = -.974) and a moderate correlation with locus of control scores (r = .683). No student in the occupational therapy group scored within the moderate-to-severe or severe range. The results did not support a relationship between codependency and choice of a caregiving-oriented profession. Further, only moderate-to-severe and severe codependency scores were indicative of low self-esteem and high external locus of control. Implications of this study suggest incorporation into the academic preparation of occupational therapy students information regarding codependency and self-assessment of codependency to facilitate awareness of the student's need to nurture others.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1514569 TI - Occupational adaptation: toward a holistic approach for contemporary practice, Part 1. AB - A theoretical perspective designed for clinical application and based on fundamental occupational therapy principles is offered. This perspective, the occupational adaptation frame of reference, is presented as an articulation of (a) a normal developmental process leading to competence in occupational functioning; (b) the process through which the benefits of occupational therapy occur; and (c) a perspective that promotes holistic practice. The person is viewed as operating occupationally through an idiosyncratic configuration of sensorimotor, cognitive, and psychosocial systems, all of which are inevitably involved in each occupational response. This occupational functioning is described as occurring through interaction of the person with a work, play and leisure, or selfcare context that has distinctive physical, social, and cultural properties (i.e., the occupational environment). Occupational adaptation is a perspective that can influence practice, education, and research. PMID- 1514570 TI - The use of electromyographic biofeedback in treating a client with tension headaches. AB - EMG biofeedback was used during a 4-week treatment program to decrease upper trapezius activity related to tension headaches. The headaches were believed to be caused by general tension and anxiety and affected the patient's ability to adequately attend to activities of daily living, including child care, homemaking, and vocational activities. The program combined deep-breathing exercises, progressive muscular relaxation exercises, resisted shoulder elevation exercises, and EMG monitoring during upper extremity tasks involving shoulder flexion. An important adjunct to clinic sessions was a home exercise program to be completed 2 to 3 times per day. In this case, the EMG biofeedback program was successful in assisting the patient to eliminate tension headaches for at least an 8-week period. At the same time, the patient reported an increased ability to attend to activities of daily living, stating that she was able to "do more around the house" and had not missed a day at work in 2 months. PMID- 1514571 TI - Health care reform. PMID- 1514572 TI - Profiling the work-hardening therapist: education and experience. PMID- 1514573 TI - Partition of occupational science and occupational therapy. PMID- 1514574 TI - Infant Neurological International Battery has high predictive validity, and test author is a pediatric neurologist. PMID- 1514575 TI - AMP deaminase binding in contracting rat skeletal muscle. AB - AMP deaminase, which hydrolyses AMP to inosine 5'-monophosphate (IMP) and NH3 at high rates during excessive energy demands in skeletal muscle, is activated when bound to myosin in vitro. We evaluated AMP deaminase binding in vivo during muscle contractions to assess whether binding 1) is inherent to deamination and found only with high rates of IMP production or simply coincident with the contractile process and 2) requires cellular acidosis. AMP deaminase activity (mumol.min-1.g-1) was measured in the supernatant (free) and 10(4)-g pellet (bound) homogenate fractions of muscle of anesthetized rats after in situ contractions to determine the percent bound. In resting muscle, nearly all (approximately 90%) AMP deaminase is free (cytosolic). During contractions when energy balance was well maintained, binding did not significantly differ from resting values. However, during intense contraction conditions that lead to increased IMP concentration, binding increased to approximately 60% (P less than 0.001) in fast-twitch and approximately 50% in slow-twitch muscle. Binding increased in an apparent first-order manner and preceded initiation of IMP formation. Further, binding rapidly declined within 1 min after cessation of intense stimulation, even though the cell remained extremely acidotic. Extensive binding during contractions was also evident without cellular acidosis (iodoacetic acid-treated muscle). Thus the in vivo AMP deaminase-myosin complex association/dissociation is not coupled to changes in cellular acidosis. Interestingly, binding remained elevated after contractions, if energy recovery was limited by ischemia. Our results are consistent with myosin binding having a role in AMP deaminase activation and subsequent IMP formation in contracting muscle. PMID- 1514576 TI - Altered kinetics of AMP deaminase by myosin binding. AB - AMP deaminase catalyzes the deamination of AMP to inosine 5'-monophosphate (IMP) and ammonia. Factors controlling the enzyme in muscle can rapidly promote high rates of IMP formation when ATP utilization exceeds supply. We evaluated whether binding of AMP deaminase to myosin, which occurs during intense contraction conditions, alters the kinetic behavior of the enzyme. Reaction kinetics of myosin-bound and free AMP deaminase were evaluated. Reaction kinetics of the free enzyme yielded a near-linear double-reciprocal plot with an expected Km of approximately 1 mM AMP concentration (AMP). In contrast, reaction kinetics of AMP deaminase became bimodal when bound to myosin. At [AMP] less than 0.15 mM, a high affinity Km (0.05-0.10 mM) with maximal velocity approximately 20% that of free enzyme was evident. At [AMP] greater than 0.15 mM, the Km and maximal velocity values were similar to that of the free enzyme. The 10- to 20-fold higher affinity Km would allow for a higher rate of AMP deamination at the low [AMP] found physiologically. AMP deaminase binding to myosin also induced a marked resistance to orthophosphate inhibition (10 mM) in the presence of 50 microM ADP. Results were similar for purified preparations of AMP deaminase bound to myosin subfragment 2 and crude extracts obtained from contracting muscle. Our results add further support to the hypothesis that AMP deaminase binding to myosin serves an important role in control of enzyme activity in contracting muscle. PMID- 1514577 TI - Changes of cytosolic Ca2+ interfere with measurements of cytosolic Mg2+ using mag fura-2. AB - In rat pancreatic and submandibular gland acini during exposure to carbachol, changes in the fluorescence emission intensity ratio (R) of acini loaded with mag fura-2 resemble changes in cytosolic Ca2+ concentration (Ca2+i) in acini loaded with fura-2. Furthermore, changes of R depend on the presence of extracellular Ca2+ (Ca2+o) but are much less influenced by changes in extracellular Mg2+ (Mg2+o). To evaluate interference with measurement of cytosolic Mg2+ (Mg2+i) by changes in Ca2+i, we determined the dissociation constant (Kd) and Hill coefficient (NH) of the Ca(2+)-mag-fura-2 and Mg(2+)-mag-fura-2 complexes in standard solutions, in intact acini after loading with the acetoxymethyl ester of mag-fura-2 (mag-fura-2/AM), and in lysates derived from acini loaded with mag fura-2/AM. The Kd of the Ca(2+)-mag-fura-2 complex in acini (determined with ionomycin) was 20.49 +/- 5.20 microM, and NH was 1.44 +/- 0.16 (n = 24). Kd of the Mg(2+)-mag-fura-2 complex in acini was 2.25 +/- 0.98 mM, and NH was 1.20 +/- 0.20 (n = 25). Mean Kd values were slightly lower in acinar lysates and in solutions of standard mag-fura-2. In acini from either gland, 1,2-bis(2 aminophenoxy)ethan-N,N,N',N'-tetraacetic acid (BAPTA) suppressed carbachol induced Ca2+i transients. The R value in stimulated acini loaded with BAPTA and mag-fura-2 increased slightly when Mg2+o was increased from less than 10 nM to 1.2 mM, suggesting that Mg2+ influx contributes to the maintenance of Mg2+i during exposure to carbachol. Under these conditions, pancreatic acinar Mg2+i is 0.53 +/- 0.14 mM (n = 5).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1514578 TI - Differential modulation of a sodium conductance in skeletal muscle by intracellular and extracellular fatty acids. AB - Voltage-activated sodium channels of cultured skeletal muscle show diametrically divergent responses to intracellular vs. extracellular exposure to free fatty acids. Intracellular exposure to 1-20 microM arachidonic acid increased the magnitude of voltage-activated sodium currents, but not potassium currents, in whole cell recordings of human primary muscle cells and in the C2C12 mouse cell line. Oleic and stearic acids also stimulated increased sodium currents. In contrast, extracellular exposure to 5-10 microM arachidonic acid reversibly inhibited inward currents. Externally applied oleic acid was a less effective inhibitor, and stearic acid (up to 20 microM) produced no inhibition. The difference in sodium current responses to intracellular vs. extracellular exposure indicates that fatty acids can modulate skeletal muscle sodium channel function by at least two different pathways. PMID- 1514579 TI - Interaction of calcium with plasma membrane of epithelial (MDCK) cells during junction formation. AB - We have previously shown that upon transferring confluent monolayers of Madin Darby canine kidney (MDCK) cells from low- to normal-Ca2+ medium, cytosolic Ca2+ increases and tight junctions (TJs) assemble and seal, but the increase in cytosolic Ca2+ does not seem to be necessary for junction formation. In the present work we establish that these are in fact two independent phenomena. We first measured unidirectional Ca2+ fluxes across the plasma membrane of MDCK cells to find suitable inhibitors and tested their effects on the ability of Ca2+ to seal the TJ. Likewise, we studied a variety of multivalent cations. We observed that 1) Ca2+ triggering of junction formation does not depend on its entering the cell, 2) cations like La3+ may impair the influx of Ca2+ without affecting the sealing of TJs, and 3) only Cd2+ is able to block both Ca2+ penetration and junction formation; however, 4) Cd2+ itself cannot trigger junction formation. We interpret that Ca2+ triggers junction formation by acting mainly on an extracellular membrane site and that this site has a higher Ca2+ selectivity than the mechanisms for Ca2+ translocation across the membrane. PMID- 1514580 TI - Acceleration of growth of cultured cardiomyocytes and translocation of protein kinase C. AB - Phorbol 12-myristate 13-acetate (PMA), norepinephrine (NE), and contraction stimulate cardiomyocyte growth (increased protein content). Differences exist in the time course and extent of protein and RNA accumulation. Cells plated at 4 x 10(6) cells/60-mm dish and arrested with 50 mM KCl demonstrated no significant growth. Treatment with PMA stimulated growth to a maximum of 17% at 48 h. In contrast, maximal stimulation of growth was 36% at 48 h and 31% at 72 h for contracting and NE-treated cells, respectively. Maximal stimulation of the capacity for protein synthesis (RNA content) was 32% for PMA-treated cells at 24 h compared with 59% and 77% for NE-treated and contracting cells, respectively, at 72 h. In support of a primary role for altered capacity in the regulation of protein synthesis, there was a significant correlation (r = 0.84) between RNA and protein contents that was independent of the stimulus used. Angiotensin II increased RNA content by 28% at 48 h but had no effect on growth up to 72 h. Growth stimulation and increased nuclear protein kinase C (PKC) activity were induced by contraction, NE, and PMA treatment and were inhibited by staurosporine (a PKC inhibitor), suggestive of a central role for PKC. PMID- 1514581 TI - Hypoxia induces glucose transporter expression in endothelial cells. AB - Endothelial cells in various tissues of the body are often exposed to hypoxic conditions. To examine the effects of sustained hypoxia on energy metabolism in endothelial cells, we have maintained bovine aortic and human umbilical vein endothelial cells in an atmosphere containing low oxygen concentrations (14 mmHg) for up to 96 h. We report here that endothelial cells maintained under these conditions upregulate their glucose transport activity, consume more glucose, and produce greater amounts of lactic acid than normoxic cells. Upregulation of glucose transport activity by hypoxic endothelial cells required several hours to occur, was associated with increased expression of mRNA and protein for the erythroid/brain form of the facilitative glucose transporter, and was not due to depletion of glucose from the medium. Prolonged treatment of endothelial cells with inhibitors or uncouplers of oxidative phosphorylation (antimycin, azide, dinitrophenol) under normoxic conditions also upregulated glucose transporter expression. These results suggest that reduced rates of oxidative metabolism may represent an important signal for cells to adapt metabolically to hypoxia. Furthermore, in our examination of endothelial cell energy metabolism, we discovered that endothelial cells contain phosphocreatine and express both the brain and muscle isozymes of creatine kinase. PMID- 1514582 TI - Depletion in nuclear spermine during human spermatogenesis, a natural process of cell differentiation. AB - Polyamines (PA), polycations present in all mammalian cells, are essential for cell proliferation and differentiation. In vitro, PA are known to bind to DNA with a high affinity. In vivo, the intimate association of endogenous PA with highly condensed chromatin has been reported. During spermatogenesis, when processes of cell proliferation and differentiation take place, the potential role of polyamines has not been studied in depth. We report here the PA levels measured in human spermatogenic cell nuclei at different stages of differentiation. Cell populations (spermatocytes and round, elongating, or elongated spermatids) were obtained after submitting human testes to a trypsin deoxyribonuclease digestion, then to a centrifugal elutriation and Percoll gradient centrifugation. A significant and progressive nuclear spermine level decrease was observed from primary spermatocytes to elongated spermatids. This release of spermine from nuclei was concomitant with three major events in mammalian spermiogenesis: the reduction of DNA transcription activity, the replacement of histone proteins by protamines, and the compaction of chromatin. This is the first report arguing a release of nuclear spermine during an in vivo physiological cell differentiation process. PMID- 1514583 TI - Chloride secretory response to extracellular ATP in human normal and cystic fibrosis nasal epithelia. AB - Chloride secretion across cystic fibrosis (CF) airway epithelia is effectively regulated by pathways associated with intracellular Ca2+ metabolism, but not by mechanisms dependent on protein kinase A or C. In a search for therapeutically useful agonists, we investigated the effects of extracellular ATP on the Cl- secretory process in human normal and CF nasal epithelial cultures with double barreled Cl- selective microelectrodes. When applied to the basolateral membrane of normal, but not CF, nasal epithelium, extracellular ATP (10(-4) M) stimulated a small increase in Cl- secretion that was primarily associated with a hyperpolarizing conductance in the basolateral membrane. In contrast, ATP applied to the apical (luminal) membrane of either normal or CF nasal epithelium stimulated a greater increase in Cl- secretion that was associated with activation of an apical membrane Cl- conductance. The increases in Cl- current and apical conductance were greater in CF tissues and attained maximal values similar to normal nasal epithelium. We conclude 1) that basolateral application of ATP indirectly induces Cl- secretion by activating a basolateral (K+) conductance and is an effective secretagogue only in normal nasal epithelium and 2) that luminally applied ATP is an effective Cl- secretagogue that activates the apical membrane Cl- conductance of normal and CF nasal epithelia to an equivalent level. PMID- 1514584 TI - Two-dimensional 31P-chemical shift imaging of intramuscular heterogeneity in exercising human forearm muscle. AB - Two-dimensional phosphorus chemical shift imaging (2D-31P-CSI) was used to investigate macroscopic heterogeneity within the flexor digitorum profundus (FDP) muscle of the human forearm during exercise. Subjects performed low-frequency steady-state finger flexion exercise at submaximal work levels using a bulb ergometer. The number of fingers actively involved in finger flexion exercise was varied in a total of 12 experiments. Active muscles could be determined by the increase of Pi and decrease of phosphocreatine observed in the localized spectra. Within the FDP, regions of active and inactive fibers were significantly different in levels of Pi and phosphocreatine (P less than 0.01) during flexion of individual fingers. Individual flexion of the index finger was found to involve only fibers in the deep region of the FDP. Fibers in the central region were found to be involved in flexion of the middle finger, and fibers in the superficial region were involved in flexion of the ring and little fingers. The results of this study demonstrate the potential of 2D-31P-CSI for in vivo investigation of intramuscular heterogeneity in human skeletal muscle. PMID- 1514585 TI - Early effects of aldosterone on apical and basolateral membrane conductances of TBM cells. AB - The early effects (1-4 h) of aldosterone on membrane conductance were studied in the TBM cells, an epithelial cell line derived from the toad urinary bladder. Aldosterone stimulated Na+ transport (measured as short-circuit current) and induced parallel increases of the amiloride-sensitive apical membrane Na+ conductance and the basolateral membrane conductance. In another set of experiments, we prevented the aldosterone-induced increase of the Na+ transport by adding amiloride to the apical solution in concentrations sufficient to reduce short-circuit current to values similar to that of matched control. The effect of aldosterone on the basolateral conductance was not inhibited. This effect was essentially due to a change of the barium-sensitive K(+)-specific conductance. We also observed that aldosterone prevented a time-dependent decline of the paracellular resistance observed in control preparations. Aldosterone induces an early increase of the basolateral membrane conductance, an effect that is not secondary to the increase of the Na+ load to the cell. PMID- 1514586 TI - Physiological fluid shear stress causes downregulation of endothelin-1 mRNA in bovine aortic endothelium. AB - We report here that the level of endothelin-1 (ET-1) mRNA from bovine aortic endothelial cells grown in vitro is rapidly (within 1 h of exposure) and significantly (fivefold) decreased in response to fluid shear stress of physiological magnitude. The downregulation of ET-1 mRNA occurs in a dose dependent manner that exhibits saturation above 15 dyn/cm2. The decrease is complete prior to detectable changes in endothelial cell shape and is maintained throughout and following alignment in the direction of blood flow. Peptide levels of ET-1 secreted into the media are also reduced in response to fluid shear stress. Cyclical stretch experiments demonstrated no changes in ET-1 mRNA, while increasing media viscosity with dextran showed that the downregulation is a specific response to shear stress and not to fluid velocity. Although both pulsatile and turbulent shear stress of equal time-average magnitude elicited the same decrease in ET-1 mRNA as steady laminar shear (15 dyn/cm2), low-frequency reversing shear stress did not result in any change. These results show that the magnitude as well as the dynamic character of fluid shear stress can modulate expression of ET-1 in vascular endothelium. PMID- 1514587 TI - Protective effect of the dimer of 16,16-diMePGB1 against KCN-induced mitochondrial failure in hepatocytes. AB - The dimer and trimer of 16,16-dimethyl-15-dehydroprostaglandin B1 (16,16 diMePGB1) previously have been shown to have protective effects on mitochondrial function. To examine the potential mechanisms involved in protection against mitochondrial failure, we have studied the effects of the dimer of 16,16-diMe PGB1 (dicalciphor) on mitochondrial function in hepatocytes exposed to KCN. Addition of micromolar concentrations of dicalciphor provided substantial protection against KCN-induced toxicity in a concentration- and time-dependent manner. Dicalciphor, however, had no effect on total or mitochondrial ATP losses in KCN-treated cells. The dimer prevented the marked loss of mitochondrial membrane potential (delta psi) and delta pH that occurs as a result of KCN treatment and prevented KCN-induced loading of phosphate in mitochondria. Furthermore, the dimer of 16,16-diMePGB1 also prevented KCN-induced mitochondrial and cellular swelling. These results demonstrate that dicalciphor protects against KCN-induced damage and that this protection is associated with regulation of specific mitochondrial ion transport functions. PMID- 1514588 TI - Volume regulation during recovery from chronic hypertonicity in brain glial cells. AB - Rat C6 glial cells undergo rapid regulatory volume increase (5-10 min) via electrolyte uptake when exposed to a hypertonic medium. With chronic exposure to hypertonicity (greater than 8 h), accumulated electrolyte is replaced partly by inositol. Inositol accumulation is brought about by upregulation of Na(+) dependent inositol transport. When C6 cells acclimated chronically to hypertonic NaCl medium were returned to isotonic conditions, inositol levels dropped slowly from 478 nmol/mg protein towards control values (117 nmol/mg protein) in 18-24 h. Inositol loss occurred in part by efflux to the external medium via a pathway distinct from the uptake mechanism. Laser light-scattering measurements demonstrated that regulatory volume decrease (RVD) is slow under these experimental conditions. In contrast, cells exposed acutely to hypertonicity swell and then undergo a rapid and nearly complete RVD when returned to isotonic medium. These results suggest that slow inositol loss is rate limiting for RVD during recovery from chronic hypertonic stress. The slow inositol loss and RVD may be due to slow turnover of the efflux mechanism and/or slow downregulation of the hypertonically stimulated inositol uptake pathway. PMID- 1514589 TI - TGF-beta 1 potentiates growth factor-stimulated proliferation of vascular smooth muscle cells in genetic hypertension. AB - We have examined the interactions between transforming growth factor-beta 1 (TGF beta 1) and epidermal growth factor (EGF), basic fibroblast growth factor (bFGF), or platelet-derived growth factor (PDGF) isoforms PDGF-AB and PDGF-BB on the proliferation of vascular smooth muscle cells isolated from the spontaneously hypertensive rat. TGF-beta 1 alone stimulated [3H]thymidine incorporation approximately twofold without a corresponding increase in cell number. In combination, TGF-beta 1 action was synergistic in further stimulating both DNA synthesis and cell proliferation 100-300% above the responses elicited by each growth factor. To gain further insight into the mechanism responsible for this potentiation, we examined the interaction between TGF-beta 1 and EGF. The synergistic interaction between TGF-beta 1 and EGF on DNA synthesis was independent of initial cell density. This effect of TGF-beta 1 was initiated early in the G1 phase of the cell cycle and did not appear to be mediated through the mobilization of Ca2+ or alterations in c-jun mRNA expression. However, in the presence of both TGF-beta 1 and EGF, there was a sustained elevation of c-myc mRNA levels over a 24-h period. These results suggest that TGF-beta 1 may interact with other growth factors in vivo to enhance their proliferative action on vascular smooth muscle of spontaneously hypertensive rats via mechanisms dependent on c-myc mRNA expression. PMID- 1514590 TI - Abundance, localization, and insulin-induced translocation of glucose transporters in red and white muscle. AB - D-Glucose protectable cytochalasin B (CB) binding to subcellular membrane fractions was used to determine glucose transporter number in red (quadriceps gastrocnemius-soleus) and white (quadriceps-gastrocnemius) rat muscle. CB binding was twofold higher in isolated plasma membranes of red than of white muscle. In contrast, the number of transporters in an isolated insulin-sensitive intracellular membrane organelle was similar in the two muscle groups. Immunoblotting and immunofluorescence microscopy with anti-GLUT4 and anti-GLUT1 antibodies indicated that both GLUT1 and GLUT4 transporter isoforms account for the higher abundance of CB binding sites in plasma membranes of red than of white muscle. Immunofluorescence localized GLUT4 to both the surface and the interior of the muscle cell and demonstrated that type I (slow twitch oxidative) and type IIa (fast twitch oxidative-glycolytic) fibers are enriched in GLUT4 protein compared with type IIb (fast twitch glycolytic) fibers. In contrast, GLUT1 reactivity was restricted to the surface of the muscle cell and was also highly enriched in the perineurial sheaths of peripheral nerves and the capsules of muscle spindles present in both red and white muscles. Insulin caused a twofold increase in CB binding in isolated plasma membranes of red or white muscles with a corresponding 40-50% decrease in CB binding in isolated intracellular membranes. These changes in CB binding were paralleled by similar changes in the membrane distribution of the GLUT4 glucose transporter isoform and in glucose transport activity measured after insulin perfusion of hindquarter muscles. In contrast, insulin did not change the distribution of either GLUT1 glucose transporters or Na(+)-K(+)-ATPase alpha 1-subunits. The molar ratio of GLUT4 to GLUT1 in red and white muscle plasma membranes was found to be 4:1 in the basal state and 7:1 in the insulin-stimulated state. These results indicate that red muscle contains a higher amount of GLUT1 and GLUT4 transporters at the plasma membrane than white muscle in the basal and insulin-stimulated states but that GLUT4 translocation does not differ between muscle types. In addition, GLUT4 expression correlates with the metabolic nature (oxidative vs. glycolytic) of skeletal muscle fibers, rather than with their contractile properties (slow twitch vs. fast twitch). PMID- 1514591 TI - Maturational changes in respiratory control through creatine kinase in heart in vivo. AB - The role of creatine kinase in regulation of myocardial respiration was studied in vivo as a function of maturation. Unidirectional creatine kinase flux (JCK), phosphocreatine to gamma-ATP, was measured in newborn lambs (age 3-9 days, n = 8) and mature sheep (age 30-60 days, n = 6) using 31P saturation transfer techniques, and total creatine kinase activity was measured using standard methods. Myocardial oxygen consumption (MVO2) was measured simultaneously via an extracorporeal shunt from the coronary sinus as cardiac work was increased via epinephrine (1-3 micrograms.kg-1.min-1). Findings were as follows: 1) baseline newborn JCK was markedly lower than in mature sheep despite higher levels of MVO2, and this could be related to a decrease in total creatine kinase activity; 2) JCK was substantially higher than the rate of ATP synthesis in both groups at baseline rates of oxygen consumption; and 3) JCK decreased significantly in newborns during increases in MVO2, whereas there was no change in flux rate in the mature sheep during even larger relative changes in work and oxygen consumption. These data imply that creatine kinase does not limit oxidative phosphorylation. However, this enzyme system probably maintains at least an indirect role in respiratory control that is a function of the myocardial developmental state. PMID- 1514592 TI - Transmucosal impedance of small intestine: correlation with transport of sugars and amino acids. AB - Transmucosal impedances of isolated perfused segments of jejunum from mice and hamsters were measured at frequencies from 10-100,000 Hz in the presence and absence of sugars and amino acids. Na-coupled transport of organic substrates caused large decreases of transmucosal impedance, reflecting contraction of cytoskeletal proteins controlling permeability of tight junctions, functional surface of basolateral membranes, and width of extracellular pathways. The observed changes of impedance were closely correlated with molar rates of Na coupled active transport rather than with molecular species. Thus amino acids and sugars having the same molar rates of active transport also have the same effects on transmucosal impedance. It is proposed that a nonspecific increase of intracellular osmotic pressure during active transport is the first step initiating cytoskeletal contraction. Cell volume regulatory responses, including increased basolateral K+ conductance and Ca2+ influx, may be subsequent steps leading to contraction of perijunctional actomyosin, formation of junctional dilatations, and exposure of lateral membranes. Enhancement of oxygen capacity of perfusion fluids (e.g., with fluorocarbon emulsion) is required to maintain viability of isolated intestinal epithelium; in plain oxygenated Ringer-HCO3 solution, the transmucosal impedance is abnormally low and cytoskeletal contractile responses to Na-coupled transport are attenuated. An electrical circuit analog is presented that simulates almost exactly the observed transmucosal impedances and provides quantitative evaluation of the effects of Na coupled transport of sugars and amino acids on resistances of tight junctions, capacitance of basolateral membranes, and postjunctional resistances of lateral intercellular spaces and villus cores. PMID- 1514593 TI - Arachidonic acid and lipoxygenase metabolites uncouple neonatal rat cardiac myocyte pairs. AB - The effects of arachidonic acid (AA) and its metabolites on the conductance (gj) of the gap junctions between neonatal rat myocardial cells was investigated. AA reduced gj in a dose- (2, 5, and 20 microM) and time-dependent fashion. Pretreatment of the cells with an inhibitor of the 5-lipoxygenase pathway, U 70344A, shifted the dose-response curve to the right; pretreatment with indomethacin, an inhibitor of the cyclooxygenase pathway, had no effect. The mean time to uncoupling was 3.7 +/- 0.3, 3.8 +/- 0.9, and 4.6 +/- 0.6 min (means +/- SE, P less than 0.05) for 5 microM AA, 5 microM AA + indomethacin, and 5 microM AA + U-70344A, respectively. Incorporation of AA into membrane phospholipids was not affected by the inhibitor. These studies suggest that complete uncoupling of the cells occurred at membrane concentrations of 3-4 mol%. The data indicate that AA and a 5-lipoxygenase metabolite uncouple neonatal rat heart cells. The data are discussed with respect to the possible underlying mechanism of uncoupling and the potential role of gap junctions in arrhythmia formation in ischemic heart disease. PMID- 1514594 TI - Na+ alters the affinity for glucose and phosphate in rat renal brush-border membranes: a study of NMR relaxation rates. AB - Transport of D-glucose (Glc) and Pi across renal microvilli brush-border membrane vesicles (BBMV) is coupled to Na+.Na+ may alter substrate binding and dissociation or the mobility of the translocator and its complexes. To evaluate substrate binding in NaCl or KCl solutions containing BBMV, we measured nuclear magnetic resonance transverse relaxation rates (1/T2) of [1-13C]Glc and 31P(i), as well as their temperature, magnetic field, and pH dependencies. The data indicate the following: 1) the alpha-anomer, but not the beta-anomer, of Glc binds to BBMV, more in the presence of Na+ than of K+; 2) interactions of P(i) with BBMV that increase its 1/T2 are significant in the presence of K+ but not of Na+; 3) temperature and magnetic field dependencies of the 1/T2 of P(i) bound to BBMV are consistent with more rapid exchange with free P(i) in the presence of Na+ than of K+; and 4) in the presence of Na+, [H+] promoted interactions of P(i) with BBMV that increase its 1/T2, probably by interfering with formation of rapidly dissociating Na(+)-P(i)-carrier complexes. In conclusion, Na+ promotes association of alpha-Glc to BBMV but promotes rapid exchange and dissociation of P(i) from BBMV. In both cases, Na+ effects coupling by altering the affinity of the cotransporters for the substrate. PMID- 1514595 TI - Stored calcium modulates inositol phosphate synthesis in cultured smooth muscle cells. AB - Cytosolic Ca2+ concentrations ([Ca2+]cyt) and [3H]inositol phosphates ([3H]InsP) were correlated while varying the Ca2+ content of the sarcoplasmic reticulum (SR) in cultured A7r5 cells at rest and during activation with [Arg8]-vasopressin (AVP). Thapsigargin (TG) raised and superfusion with 0 Ca2+ lowered [Ca2+]cyt, but both treatments decreased SR Ca2+ and AVP-evoked Ca2+ transients. Neither TG nor 0 Ca2+ affected basal [3H]InsP, but both treatments increased AVP-evoked synthesis of [3H]InsP. Exposure for several minutes to 40 mM K+ solution, BAY K 8644, or low-Na+ solution all elevated [Ca2+]cyt and, thereby, increased SR Ca2+, as manifested by augmented AVP-evoked Ca2+ transients. In all three cases, AVP evoked, but not basal, [3H]InsP were reduced. The inhibitory effect of 40 mM K+ on AVP-evoked [3H]InsP synthesis was blocked when SR Ca2+ uptake was prevented by TG. Brief (30-s) exposures to 40 mM K+, which elevated [Ca2+]cyt but not SR Ca2+ loading, did not modify AVP-evoked [3H]InsP synthesis or Ca2+ transients. These results demonstrate an inverse relationship between SR Ca2+ content and evoked [3H]-InsP synthesis. Moreover, they suggest that SR Ca2+ may serve as a signal that modulates sarcolemmal [3H]InsP formation. PMID- 1514596 TI - Transient myosin phosphorylation at constant Ca2+ during agonist activation of permeabilized arteries. AB - Norepinephrine (NE) plus guanosine triphosphate (GTP) increases myofilament Ca2+ sensitivity in alpha-toxin-permeabilized smooth muscle. We used alpha-toxin permeabilized rabbit mesenteric arteries to determine the temporal relationships among force, myosin light chain (MLC) phosphorylation, stiffness, and shortening velocity during contractions in response to Ca2+ alone and to the same [Ca2+] in the presence of NE plus GTP. The addition of NE plus GTP caused a marked increase in the tonic contraction but only transiently elevated the level of MLC phosphorylation over that observed in the presence of Ca2+ alone. NE plus GTP induced similar increases in force and stiffness, but shortening velocity depended solely on the [Ca2+]. A regulated MLC phosphatase could explain the initial increase in force and MLC phosphorylation, but not the maintenance of enhanced force while MLC phosphorylation levels fell to values similar to those in response to Ca2+ alone. Therefore, additional elements must be involved in the maintenance of the receptor and G protein-dependent increase in myofilament Ca2+ sensitivity. PMID- 1514597 TI - Immunofluorescence localization of the Na-Ca exchanger in heart cells. AB - We investigated the localization of the Na-Ca exchanger in fixed, isolated heart cells from rat and guinea pig using immunocytochemical methods with epifluorescence and confocal microscopy. We found that the Na-Ca exchanger is distributed throughout all membranes in contact with the extracellular space, including the sarcolemma, the transverse tubules (T-tubules), and the intercalated disks. Microscopic nonuniformities in the fluorescent labeling appear to reflect varying views of the membranes containing Na-Ca exchanger protein. Confocal thin-section imaging reveals a regular grid of discrete foci of fluorescence, which represent Na-Ca exchanger in T-tubules viewed en face. These foci are 1.80 +/- 0.01 microns apart from sarcomere to sarcomere and are aligned with the Z-line. Along each Z-line, these foci are spaced at 1.22 +/- 0.11 microns intervals. Longitudinal sections of the sarcolemma-T-tubule junction show a comblike appearance, with T-tubules extending inward from the heavily labeled sarcolemma. Our finding that the Na-Ca exchanger is widely distributed over the cell surface may provide further insight into the role of Na-Ca exchange in the heart. PMID- 1514598 TI - Regulation of acute parathyroid hormone release in normal humans: combined calcium and citrate clamp study. AB - The objective of the present study was to elucidate the dynamics of parathyroid hormone regulation, with particular reference to the mechanism controlling the acute parathyroid hormone release. Through utilization of the citrate clamp technique and the calcium clamp technique we were able, in a standardized way, to stimulate and suppress the parathyroid hormone secretion. Precise bedside measurements of blood ionized calcium and measurements of intact parathyroid hormone were performed. Twelve healthy young volunteers participated in two trials 6-12 wk apart, a citrate clamp (delta-blood ionized calcium -0.19 mmol/l) and a calcium plus citrate clamp (delta-blood ionized calcium +0.22 mmol/l and 0.19 mmol/l). During the citrate clamp, preceded by normal calcemia, serum intact parathyroid hormone peaked to a maximum after 5-10 min, four to six times above baseline concentration and then declined to a steady state two to three times above baseline concentration. During the citrate clamp, preceded by hypercalcemia induced by a calcium clamp, serum intact parathyroid hormone also peaked immediately to about five to nine times above its suppressed level, approximately two times above the baseline concentration. Subsequently, serum intact parathyroid hormone declined to a steady state just below the baseline concentration. In conclusion, within the range studied, the mechanism eliciting the acute serum intact parathyroid hormone release from its depot is a fall in blood ionized calcium, not the absolute concentration of ionized calcium. PMID- 1514599 TI - Effects of epinephrine on insulin-mediated glucose uptake in whole body and leg muscle in humans: role of blood flow. AB - In vivo insulin-mediated glucose uptake (IMGU) occurs chiefly in skeletal muscle, where it is determined by the product of arteriovenous glucose difference (delta AVG) and blood flow (BF) rate into muscle. Epinephrine (Epi) reduces the rate of IMGU in whole body. To examine whether this is due to a reduction in delta AVG across or BF into skeletal muscle we constructed insulin dose-response curves for whole body IMGU and leg muscle IMGU- using euglycemic clamp ((+)[3-3H]glucose infusion) and leg balance techniques during insulin infusions ranging from 10 to 1,200 mU.m-2.min-1. We studied six subjects [wt 70 +/- 2 (SE) kg] during an Epi infusion at a single rate of 0.002 mg.kg-1.min-1 and six subjects (70 +/- 3 kg) during a saline infusion alone. Maximum whole body glucose uptake (WBGU) was similar during Epi and saline infusions [71.4 vs. 73.6 mmol.kg-1.min-1, P = not significant (NS)]. Compared with saline, maximum delta AVG was decreased during Epi infusion (1.04 vs. 1.31 mM, P less than 0.01). Compared with saline alone maximum leg BF was increased (5.3 vs. 4.3 dl/min, P less than 0.01) during Epi infusion. Thus maximum leg glucose uptake (LGU) was similar (696 vs. 821 pmol.leg 1.min-1, P = NS) during infusion of Epi and saline, respectively. Half-maximal effective dose for insulin's effect to stimulate WBGU, delta AVG, BF, and LGU was increased two- to threefold during Epi vs. saline infusions (P less than 0.01 for all values).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1514600 TI - PDGF induces tyrosine phosphorylation in osteoblast-like cells: relevance to mitogenesis. AB - We have studied the association between protein tyrosine phosphorylation and the mitogenic effect induced by platelet-derived growth factor (PDGF) in the osteoblast-like cell line MC3T3-E1. PDGF caused a dose-dependent increase in [3H]thymidine incorporation in MC3T3-E1 cells, reaching a plateau at 10 ng/ml. Vanadate, a potent phosphatase inhibitor, induced a twofold increase in thymidine incorporation. The combination of vanadate and PDGF resulted in a dose-dependent synergistic effect on thymidine incorporation. Genistein, a tyrosine kinase inhibitor, inhibited in a dose-related manner (2-20 microM) the mitogenic effect induced by either PDGF or the combination of vanadate and PDGF. These observations suggest that tyrosine kinases are involved in mediating the mitogenic effect of PDGF in these cells. PDGF treatment of MC3T3-E1 cells and subsequent immunoblotting with antiphosphotyrosine antibodies resulted in a marked phosphorylation of the PDGF receptor. Vanadate had a lesser effect on PDGF receptor phosphorylation, but given together with PDGF it induced a significant increase in the intensity of receptor phosphorylation. Preincubation with genistein abrogated these effects. Taken together, these findings indicate a direct correlation between thymidine incorporation and tyrosine phosphorylation in MC3T3-E1 cells and suggest that tyrosine phosphorylation plays a role in PDGF induced mitogenic activity in osteoblast-like cells. PMID- 1514601 TI - Leucine kinetics in fed low-birth-weight infants: importance of splanchnic tissues. AB - Whole body Leu kinetics were determined in fed low-birth-weight (LBW) infants. To assess the importance of first-pass splanchnic extraction of ingested amino acids, two tracers were simultaneously infused by intravenous (L-[1-13C]Leu) and intragastric (L-[5,5,5-2H3]Leu) routes in 13 LBW infants [1,742 +/- 169 (SE) g] fed with protein-enriched human milk (protein intake 3.23 +/- 0.97 g.kg-1.day-1). Splanchnic extraction estimated from plasma [2H3]Leu appearance was 48.2 +/- 15.6% of Leu intake. Total Leu flux, endogenous Leu flux (index of protein catabolism), and nonoxidative Leu disposal (NOLD, index of protein synthesis) were 3.45 +/- 0.57, 1.90 +/- 0.74, and 2.54 +/- 0.62 mumol.kg-1.min-1, respectively. Higher estimates were obtained when using alpha-ketoisocaproate as a precursor pool. There was a wide individual variation of protein intake due to the use of human milk, and, over this range, Leu intake was correlated negatively with endogenous Leu flux (r = 0.88, P less than 0.01) whereas NOLD remained fairly constant. Thus, in LBW infants, 1) splanchnic extraction is two times as high as in adults and might reflect an elevated splanchnic protein turnover and 2) increasing protein intake probably promotes protein gain mainly by inhibiting protein catabolism. PMID- 1514602 TI - Spatial and temporal thyrocyte response to TSH: a computer-assisted image analysis. AB - Pseudopods at the apical pole of porcine thyroid monolayers in culture were considered as reflecting individual thyrocyte responses to thyrotropin (TSH) stimulation. Scanning electron microscopy and computer-assisted image analysis showed that whatever TSH stimulation was used, the pseudopods were characterized by two populations: P1 with small diameters (2 microns) and P2 with greater diameters (5 microns). The density of P1 rapidly increased to reach a plateau, while P2 continuously increased during stimulation. Two-dimensional pseudopod patterns were compared with random point distributions by means of two topographical parameters: the interpseudopod distances and angles. A factorial analysis of experimental distribution of pseudopods obtained after increasing stimulation times displayed a shift from a nonrandom (10-20 min) to a random (60 90 min) distribution. Clusters of three pseudopods characterized by short distances (6-9 microns) and equilateral organization (angles 40-60 degrees) were observed after a 10-min stimulation. These results suggested that early thyrocyte response to TSH stimulation is characterized by interrelations between three adjoining cells, with the thyrocyte response later appearing as random. PMID- 1514603 TI - Platelet catecholamine contents as related to trait anxiety and aerobic fitness. AB - Platelet catecholamines (CA) are derived from plasma and are considered as a cumulative index of sympathoadrenal activity. We investigated whether trait anxiety (TA) and aerobic fitness, two interrelated long-term determinants of sympathoadrenal activity, affect platelet CA concentration as measured in rest and after acute increments of plasma epinephrine (Epi). For that purpose, platelet CA were measured 15 min before and after Epi infusion (5-160 ng.kg-1.min 1, increased in 6 steps) in 45 healthy male students with high (n = 21) and low (n = 24) TA, of whom maximal aerobic power (VO2max) was assessed. Plasma CA and electrolytes were measured during each infusion rate. Epi infusion significantly raised platelet Epi by 67% and decreased platelet and plasma norepinephrine (NE) by 23 and 17%. Plasma potassium significantly decreased by 32% and plasma sodium slightly increased. Platelet Epi increase was inversely related to basal platelet Epi (r = -0.58, P less than 0.001). Platelet NE decrease was positively associated with basal platelet NE and plasma potassium levels (r = 0.50, P less than 0.01). TA and VO2max were not related to basal levels and responses of electrolytes and platelet NE. VO2max was correlated with platelet Epi increase in low TA (r = 0.62, P = 0.002), whereas no such relationship existed in high TA (r = 0.008). We conclude that fitness positively influences platelet Epi accumulation, but that high TA interferes with this relationship. PMID- 1514604 TI - Epinephrine's ketogenic effect in humans is mediated principally by lipolysis. AB - To quantify epinephrine's effects on acetoacetate and beta-hydroxybutyrate kinetics, we infused subjects with 0.3 and 2.5 micrograms/min epinephrine, either alone or with a concomitant somatostatin infusion with insulin, glucagon, and growth hormone replaced at postabsorptive levels (islet clamp). Additional subjects received no epinephrine but sequential infusions of heparin plus 10% Intralipid at rates of 0.5 and 3.0 ml/min. Both epinephrine and Intralipid increased ketone body appearance (unaffected by islet clamp), augmented the interconversion rates between ketone bodies and, during the 2.5 micrograms/min infusion, caused a marked increase in beta-hydroxybutyrate appearance. The fraction of plasma free fatty acid (FFA) flux appearing as plasma ketones increased from 6 to 7% in the basal state to 11% at the high-epinephrine infusion. This fraction was also unaffected by the islet clamp and was not different from values obtained at similar Intralipid plus heparin-induced elevations in plasma FFA levels. We conclude that epinephrine's ketogenic effect in humans is primarily the result of its lipolytic effect, is accompanied by a significantly increased rate of ketone body interconversion, is manifest largely as an increase in plasma beta-hydroxybutyrate appearance at high plasma epinephrine values, and is not limited by portal insulin at post-absorptive levels. PMID- 1514605 TI - Forearm ketone body metabolism in normal and in insulin-dependent diabetic patients. AB - In insulin deficiency, there is excessive arterial delivery of free fatty acid (FFA) to muscles where they are converted to acetoacetyl-CoA and acetyl-CoA. These intermediates may be metabolized further to acetoacetate and beta hydroxybutyrate, which can be released into the venous circulation. When ketone body (KB) tracers are infused in vivo, they are diluted across muscle tissue. This dilution may be due to 1) KB newly formed within muscle (ketogenesis); 2) exchange of tracer between labeled and unlabeled acetyl-CoA and acetoacetyl-CoA, intermediates common to the metabolism of both FFA and KB (pseudoketogenesis). Thus this study assessed whether such label exchange could be detected across the human forearm and whether an increased delivery of FFA in insulin-sufficient controls provoked dilution of labeled KB tracer comparable to that observed in insulin-deficient diabetics. Five normal and five insulin-dependent diabetic (IDDM) subjects were infused with labeled [3,4-13C2]-acetoacetate. [13C]KB enrichments were lower in forearm vein than in the artery, and dilution of labeled KB was always higher than that which could be explained by arterial venous differences of unlabeled KB. When arterial FFA concentrations in normals were raised (Intralipid+heparin) to values comparable to those of the diabetics, no additional increase in forearm arteriovenous dilution of labeled KB was observed. Neither in the basal state nor under conditions of increased plasma FFA were we able to detect venous appearance of KB labeled in the first and in the second carbon atoms, a necessary consequence of pseudoketogenesis.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1514606 TI - Origin and disposal of 1,5-anhydroglucitol, a major polyol in the human body. AB - The origin and disposal of 1,5-anhydro-D-glucitol (AG), one of the main polyols found in the human body, was studied in normal subjects and diabetic patients. AG was detected in various kinds of foods. The mean AG supplement through foods was estimated to be approximately 4.38 mg/day, which was compatible with that calculated in a food analysis (average 0.22 mg AG/100 kcal in Japanese foods) on eight healthy subjects. The mean AG excretion in urine was approximately 4.76 mg/day in these subjects. Excretion into stools was negligible. From observations on the patients without oral supplement of AG, 0.4 mg of daily de novo synthesis of AG was strongly suggested. It was also implied that urinary AG excretion occurred soon after food ingestion and that its amount was closely correlated with daily supplement through foods. Thus the fundamental kinetics of AG were recognized as follows: 1) AG in the body originates mainly from foods and is well absorbed in the intestine, 2) AG is little degraded and metabolized in the body, and 3) an equilibrium exists between oral supplement plus a small but steady amount of de novo synthesis and excretion in urine. PMID- 1514607 TI - Amylin and insulin in rat soleus muscle: dose responses for cosecreted noncompetitive antagonists. AB - Increasing concentrations of amylin progressively depressed the maximal insulin stimulated radioglucose incorporation into soleus muscle glycogen, but did not substantively change the EC50 (range 0.78 to 1.52 nM); these findings show noncompetitive, insurmountable antagonism of insulin action by amylin. The results from 36 combinations of different insulin and amylin concentrations were used to construct a response surface that can be used to predict the response for any combination of insulin and amylin concentration. The predicted response to a constant ratio of insulin and amylin concentration is a bell-shaped curve. The experimentally determined response to increasing amounts of an amylin-insulin mixture (molar ratio of 0.14:1, within the range measured for pancreatic secretion and plasma levels) gave a bell-shaped response rather than the sigmoidal response seen with insulin alone. The amylin dose-response relation in the soleus system provides a useful bioassay for amylin agonists. The dose response for highly purified, synthetic human amylin obtained by measuring amylin concentrations by radioimmunoassay in the incubation medium gave an EC50 of 456 pM (+/- 0.18 log units). Human amylin had a potency greater than or equal to that of human insulin in this highly insulin-sensitive preparation. PMID- 1514608 TI - Trophic action of local intraileal infusion of insulin-like growth factor I: polyamine dependence. AB - Experiments were performed to determine potential growth-promoting effects of human recombinant insulin-like growth factor I (hrIGF-I) in the gastrointestinal tract. IGF-I and IGF-II, but not insulin, were potent (half-maximal effective concentration 0.3 nM) and efficacious inducers of the growth-related enzyme ornithine decarboxylase (ODC) in the gut-derived cell line IEC-6. Maximal ODC induction was observed after treatment of cells with 10 nM IGF-I. In whole animal experiments, bolus intraileal injection of 10 nM hrIGF-I in anesthetized rats induced a 300% increase in ileal mucosal ODC activity, which was sensitive to inhibition with difluoromethylornithine (DFMO). Rats were implanted intraperitoneally with osmotic minipumps filled with 0.9% NaCl or 10 nM IGF-I that was delivered to the ileal lumen by a short Silastic catheter. Sixty-six hours of 1 microliter/h intraluminal IGF-I infusion produced an approximate doubling of mucosal wet weight (NaCl 50 mg vs. IGF-I 102 micrograms/2 cm mucosa) and total mucosal RNA, DNA, and protein content over that in rats that were infused with NaCl. Intraperitoneal treatment with 200 mg/kg DFMO three times per day had little effect on ileal mucosal mass, but completely inhibited the trophic response to IGF-I infusion. IGF-I infusion had no effect on body weight. PMID- 1514609 TI - Is there a role for the adrenals in the development of hypercholesterolemia in Zucker fatty rats? AB - We tested the hypothesis that hypercorticosteronemia causes the hypercholesterolemia in young developing "fatty" rats. Obesity induced increases in corticosterone. Insulin, glucose, body weight, average daily food intake, plasma triglyceride, plasma phospholipids, liver weight, liver triglyceride, various adipose tissue parameters, and liver hydroxymethylglutaryl coenzyme A (HMG-CoA) reductase activity were all ameliorated by adrenalectomy. Adrenalectomy exacerbated the hypercholesterolemia in obese animals and induced it in lean rats. Changes or lack of change in hepatic microsomal cholesterol, HMG-CoA reductase, and 7 alpha-hydroxylase, combined with the adrenalectomy-induced curtailment of tissue storage of cholesterol in adipose tissue, all contribute to the hypercholesterolemia caused by adrenalectomy. We suggest a mechanism whereby this may be related to elevated hepatic very low-density lipoprotein secretion rates. The elevated HMG-CoA reductase activity in obese rats results from the lower liver microsomal free cholesterol content. We conclude that the absence of glucocorticoids does not directly reduce plasma cholesterol in obese Zucker rats. The surprising elevation of cholesterol by adrenalectomy is due to other prevailing mechanisms in liver and adipose tissue, which curtail their capacity to store cholesterol. PMID- 1514610 TI - Spontaneous physical activity and obesity: cross-sectional and longitudinal studies in Pima Indians. AB - Healthy, nondiabetic Pima Indians [103 males, 77 females; 27 +/- 6 (SD) yr, 97 +/ 25 kg, 33 +/- 9% body fat] were studied in a respiratory chamber in which spontaneous physical activity (SPA) was measured by two microwave sensors. SPA, defined as the percentage of time the subjects were active, varied widely from 4.4 to 17.5%. It was higher in males (9.3 +/- 2.0%) than in females (8.6 +/- 2.3%; P less than 0.05) and was not related to body fatness in either sex. However, SPA accounted for a significant portion of the daily energy expenditure (24-h EE) in males (1,389 +/- 423 kJ/day) and females (1,163 +/- 351 kJ/day) and correlated positively with 24-h EE adjusted for differences in fat-free mass, fat mass, age, and sex (r = 0.42, P less than 0.0001). In 88 siblings, family membership accounted for 57% of the variance in SPA (r(i) = 0.57, P less than 0.02). Body composition was reassessed in a subgroup of 123 subjects (65 males, 58 females) 33 +/- 14 mo later. In males only, SPA correlated inversely to the rate of subsequent body weight change (r = -0.25, P less than 0.05) and the rate of fat-mass change (r = -0.35, P less than 0.005). We conclude that spontaneous physical activity is a familial trait that may play a role in the pathogenesis of obesity. PMID- 1514611 TI - Differential effects of interleukin-1 and tumor necrosis factor on ketogenesis. AB - To determine the role of cytokines in mediating the decrease in ketones associated with infection, we studied the effect of endotoxin (LPS), interleukin 1 (IL-1), and tumor necrosis factor (TNF) on serum and hepatic ketone body levels (KB), serum free fatty acids (FFA), and hepatic malonyl-CoA levels. LPS decreased serum and hepatic KB in C57Bl/6 (LPS sensitive) mice, whereas it had little effect in C3H/HeJ (LPS resistant) mice, whose macrophages lack the ability to produce IL-1 and TNF in response to LPS, suggesting that IL-1 and TNF may mediate this effect. IL-1 and TNF decreased serum KB in both strains of mice. As seen with LPS, IL-1 decreased hepatic KB, whereas TNF had no such effect. LPS, IL-1, and TNF increased hepatic malonyl-CoA levels. TNF acutely raised serum FFA, whereas LPS and IL-1 did not. Postulating that the TNF-induced increase in FFA overrides the inhibitory effect of malonyl-CoA on fatty acid oxidation and ketogenesis, we used R-2-phenylisopropyladenosine to block TNF-induced lipolysis and demonstrated that in the absence of increased fatty acid flux, TNF inhibits KB formation. As seen with LPS, IL-1, but not TNF, decreased KB in the fasting state. These data suggest that IL-1 and TNF may mediate the antiketogenic effect of infection and that IL-1 has properties closest to that of LPS. PMID- 1514612 TI - Selective reduction of creatine kinase subunit mRNAs in striated muscle of diabetic rats. AB - Creatine kinase (CK) is important for energy transfer and is composed of mitochondrial (mitCK), muscle (MCK), and brain (BCK) subunits, each being the product of separate nuclear genes. The concentrations of MCK and BCK mRNAs have been shown to decrease in streptozotocin-hypoinsulinemic rat hearts, and in this report, we examined in detail the diabetic effect on CK gene expression in cardiac muscle and in two types of skeletal muscle. The level of sarcomeric mitCK mRNA was not altered in the diabetic myocardium, but was reduced by 86 and 67% in diabetic slow-twitch soleus muscle and fast-twitch extensor digitorum longus (EDL) muscle, respectively. MCK mRNA was also lowered in diabetic soleus muscle by 56%, while it remained at control levels in diabetic EDL. In both skeletal muscles, at either state, BCK mRNA was not detectable. There was a 33% decrease in total CK activity in diabetic cardiac and soleus muscle, but not in EDL. Diabetes thus exerts a widespread, muscle type-dependent adverse effect on CK expression that we found to be insulin therapy revertible. This study adds to our understanding of defective energy transduction in diabetic muscle. PMID- 1514613 TI - Suppression of muscle protein turnover and amino acid degradation by dietary protein deficiency. AB - To define the adaptations that conserve amino acids and muscle protein when dietary protein intake is inadequate, rats (60-70 g final wt) were fed a normal or protein-deficient (PD) diet (18 or 1% lactalbumin), and their muscles were studied in vitro. After 7 days on the PD diet, both protein degradation and synthesis fell 30-40% in skeletal muscles and atria. This fall in proteolysis did not result from reduced amino acid supply to the muscle and preceded any clear decrease in plasma amino acids. Oxidation of branched-chain amino acids, glutamine and alanine synthesis, and uptake of alpha-aminoisobutyrate also fell by 30-50% in muscles and adipose tissue of PD rats. After 1 day on the PD diet, muscle protein synthesis and amino acid uptake decreased by 25-40%, and after 3 days proteolysis and leucine oxidation fell 30-45%. Upon refeeding with the normal diet, protein synthesis also rose more rapidly (+30% by 1 day) than proteolysis, which increased significantly after 3 days (+60%). These different time courses suggest distinct endocrine signals for these responses. The high rate of protein synthesis and low rate of proteolysis during the first 3 days of refeeding a normal diet to PD rats contributes to the rapid weight gain ("catch up growth") of such animals. PMID- 1514614 TI - Dietary protein deficiency reduces lysosomal and nonlysosomal ATP-dependent proteolysis in muscle. AB - When rats are fed a protein deficient (PD) diet for 7 days, rates of proteolysis in skeletal muscle decrease by 40-50% (N. E. Tawa, Jr., and A. L. Goldberg. Am. J. Physiol. 263 (Endocrinol. Metab. 26): E317-325, 1992). To identify the underlying biochemical adaptations, we measured different proteolytic processes in incubated muscles. The capacity for intralysosomal proteolysis, as shown by sensitivity to methylamine or lysosomal protease inhibitors, fell 55-75% in muscles from PD rats. Furthermore, extracts of muscles of PD rats showed 30-70% lower activity of many lysosomal proteases, including cathepsins B, H, and C, and carboxypeptidases A and C, as well as other lysosomal hydrolases. The fall in cathepsin B and proteolysis was evident by 3 days on the PD diet, and both returned to control levels 3 days after refeeding of the normal diet. In muscles maintained under optimal conditions, 80-90% of protein breakdown occurs by nonlysosomal pathways. In muscles of PD rats, this ATP-dependent process was also 40-60% slower. Even though overall proteolysis decreased in muscles of PD rats, their capacity for Ca(2+)-dependent proteolysis increased (by 66%), as did the activity of the calpains (+150-250%). Thus the lysosomal and the ATP-dependent processes decrease coordinately and contribute to the fall in muscle proteolysis in PD animals. PMID- 1514615 TI - Soluble and particulate phenylethanolamine N-methyltransferase in hypothalamus of diabetic rats. AB - Experimental diabetes increases total phenylethanolamine N-methyltransferase (PNMT) activity in the medulla-pons but not in the hypothalamus. In this study diabetes was induced with streptozotocin (65 mg/kg) in male Sprague-Dawley rats. Twenty-eight days after treatment there were no differences in soluble PNMT activity in the hypothalamus of diabetics and controls, but PNMT activity in a membrane-associated (particulate) fraction of hypothalamus was evaluated approximately twofold in tissues of diabetic animals compared with controls. A specific PNMT inhibitor, incubated with tissue extracts of control rats, abolished greater than 90% of particulate PNMT activity in the hypothalamus but reduced soluble PNMT activity in the hypothalamus by only 47%. These findings indicate that membrane-associated PNMT activity in rat hypothalamus differs from soluble hypothalamic PNMT in the in vitro response to an inhibitor and the in vivo response to diabetes and suggest the importance of separating subcellular hypothalamic fractions prior to assay of PNMT. PMID- 1514616 TI - Effects of prior exercise on the action of insulin-like growth factor I in skeletal muscle. AB - Prior exercise increases insulin sensitivity for glucose and system A neutral amino acid transport activities in skeletal muscle. Insulin-like growth factor I (IGF-I) also activates these transport processes in resting muscle. It is not known, however, whether prior exercise increases IGF-I action in muscle. Therefore we determined the effect of a single exhausting bout of swim exercise on IGF-I-stimulated glucose transport activity [assessed by 2-deoxy-D-glucose (2 DG) uptake] and system A activity [assessed by alpha-(methylamino)isobutyric acid (MeAIB) uptake] in the isolated rat epitrochlearis muscle. When measured 3.5 h after exercise, the responses to a submaximal concentration (0.2 nM), but not a maximal concentration (13.3 nM), of insulin for activation of 2-DG uptake and MeAIB uptake were enhanced. In contrast, prior exercise increased markedly both the submaximal (5 nM) and maximal (20 nM) responses to IGF-I for activation of 2 DG uptake, whereas only the submaximal response to IGF-I (3 nM) for MeAIB uptake was enhanced after exercise. We conclude that 1) prior exercise significantly enhances the response to a submaximal concentration of IGF-I for activation of the glucose transport and system A neutral amino acid transport systems in skeletal muscle and 2) the enhanced maximal response for IGF-I action after exercise is restricted to the signaling pathway for activation of the glucose transport system. PMID- 1514617 TI - Metabolic regulation in peripheral tissues and transition to increased gluconeogenic mode during prolonged exercise. AB - To assess the means by which peripheral metabolism facilitates the transition to a gluconeogenic state, dogs were studied during 150 min of moderate treadmill exercise. Metabolism in the working hindlimb was assessed with arteriovenous difference and isotopic techniques (n = 9). In a separate group (n = 6), hepatic metabolism was assessed using arteriovenous differences. Limb glucose uptake (LGU) and oxidation (GOX) rose from 33 +/- 10 and 5 +/- 2 to 101 +/- 20 and 54 +/ 15 mumol/min at 10 min of exercise. LGU continued to rise (151 +/- 21 mumol/min at 150 min), while GOX declined. Nonoxidative glucose metabolism (GNOX) was 28 +/ 10 mumol/min at rest and 47 +/- 24 and 108 +/- 16 mumol/min at 10 and 150 min of exercise. Limb nonglycemic (predominantly glycogen) pyruvate formation rose from 52 +/- 22 to 198 +/- 54 and 242 +/- 74 mumol/min at 10 and 150 min of exercise. The gradual increase in GNOX and the high glycogenolytic rate were paralleled by accelerated lactate, pyruvate, and glutamine releases. Limb glycerol release rose promptly and remained elevated during exercise. Plasma nonesterified fatty acids (NEFAs) rose gradually and paralleled the gradual rise in GNOX (r = 0.93). The resulting rise in hepatic NEFA delivery was highly correlated to hepatic O2 uptake (r = 0.87), hepatic vein lactate-to-pyruvate ratio (r = 0.90), and intrahepatic gluconeogenic efficiency (r = 0.96). In summary, during exercise, 1) the primary fate of the added glucose consumed by the working limb is initially oxidation, but becomes GNOX as exercise duration progresses; 2) glycogenolysis rises promptly, but attains its highest rate at the end of exercise; 3) the late increases in GNOX and glycogenolysis relate to an increased gluconeogenic precursor release from the working limb; 4) although lipolysis increases promptly and is sustained, circulating NEFAs rise only gradually; and 5) the gradual rise in plasma NEFAs is highly correlated to the shift from GOX to GNOX and the adjustments in hepatic metabolism that are necessary for the full gluconeogenic response. PMID- 1514618 TI - Stimulation of angiotensinogen mRNA levels in rat pituitary by estradiol. AB - Angiotensin II (ANG II) is a putative paracrine hormone in the anterior pituitary. Angiotensinogen mRNA, however, is not detectable by Northern blot hybridization, suggesting that ANG II may not be synthesized within the pituitary. An alternative explanation may be that angiotensinogen gene activity is low under normal conditions, with angiotensinogen mRNA being below the level of detection. Utilizing a sensitive solution hybridization method, we sought to determine whether angiotensinogen mRNA could be detected in pituitaries from normal male rats or ovariectomized (OVX) rats treated with estradiol (E2) for 4 days. Very low levels of angiotensinogen mRNA were detected from male or OVX rat pituitaries, but E2 treatment resulted in a marked dose-dependent increase in pituitary angiotensinogen mRNA levels. Levels of angiotensinogen within the pituitary were not significantly different after the E2 treatment. Angiotensinogen mRNA levels in liver and brain were much higher than in the pituitary but were not altered significantly by the chronic E2 treatment. These results are consistent with the local synthesis of angiotensinogen in the pituitary and further suggest that pituitary angiotensinogen gene transcription is regulated by estrogen. PMID- 1514619 TI - Effect of aging and exercise on GLUT-4 glucose transporters in muscle. AB - This study was conducted to investigate whether changes in muscle glucose transporter GLUT-4 protein might be associated with a previously reported deterioration in glucose tolerance with aging, and, furthermore, to determine whether exercise training could increase GLUT-4 protein levels in older animals. GLUT-4 protein concentration was measured in soleus, gastrocnemius, and extensor digitorum longus muscles of trained (10 or 15 wk treadmill running) and untrained young (6-8 mo), middle-aged (15-17 mo), and old (27-29 mo) Fischer 344 rats. All GLUT-4 protein values were expressed as a percent of the mean for the young untrained group. Two-way analysis of variance demonstrated significant main effects of both training and aging in the gastrocnemius and soleus muscles. Exercise training produced significant increases in GLUT-4 protein in the soleus muscle of young (273 +/- 32.9 vs. 100 +/- 38.5%) and middle-aged rats (215 +/- 19.9 vs. 108 +/- 33.2%) compared with sedentary controls. Similar significant increases were also found in the gastrocnemius muscle of young (169 +/- 20.1 vs. 100 +/- 5.8%) and middle-aged rats (167 +/- 46.7 vs. 60 +/- 7.9%) with training. In the oldest rats, GLUT-4 was not significantly increased with training, but the trend toward an increase was apparent in all three muscle types. The main effect of aging was primarily due to a statistically significant difference between the old trained and young trained rats. A trend toward decreased GLUT-4 with aging was apparent in the untrained animals, but this was not statistically significant. PMID- 1514620 TI - Effect of total parenteral nutrition, systemic sepsis, and glutamine on gut mucosa in rats. AB - The effect of the combination of total parenteral nutrition (TPN) and systemic sepsis on mucosal morphology and protein synthesis was investigated. Rats were given a standard TPN mixture consisting of glucose (216 kcal.kg-1.day-1), lipid (24 kcal.kg-1.day-1), and amino acids (1.5 g N.kg-1.day-1) for 5 days. On the 5th day the rats (n = 37) were randomized into four groups according to diet as follows: 1) control nonseptic on standard TPN, 2) control nonseptic on TPN with glutamine, 3) septic on standard TPN, and 4) septic with the TPN supplemented with glutamine. Twenty hours after the injection of Escherichia coli, the rats were given a 4-h constant infusion of [U-14C]leucine to determine the mucosal fractional protein synthesis rates. The following results were obtained. 1) Histological examination showed that systemic sepsis caused tissue damage to the ileum and jejunum. 2) Glutamine supplementation attenuated these changes. 3) There were no visible changes to the colon either from glutamine supplementation or sepsis. 4) Sepsis was associated with an increase in mucosal protein synthesis and decreased muscle synthesis. 5) Addition of glutamine to the TPN mix further increased protein synthesis in the intestinal mucosa of septic rats. PMID- 1514621 TI - Apolipoprotein expression and cellular differentiation in Caco-2 intestinal cells. AB - Caco-2 cells, cultured for 18 days on porous filter supports and conventional plastic culture dishes, were used to study the effects of cellular differentiation on the expression of apolipoprotein (apo) genes. Media of filter grown cells accumulated more apo B as apo B-48 and contained three times the amount of edited apo B mRNA compared with plastic-grown cells. The accumulation of apo A-I by media of plastic-grown cells was higher than accumulation by filter grown cells, despite similar concentrations of apo A-I mRNA. The apo A-IV was detectable in the culture media earlier with filter-grown cells compared with plastic-grown cells, despite similar apo A-IV mRNA concentrations. Plastic-grown cells contained more apo E mRNA, and their media accumulated more apo E than filter-grown cells. With the exception of apo A-I, apo gene expression changed with Caco-2 cell differentiation to resemble more closely the patterns seen in adult enterocytes. There were no effects or minimal effects of added retinoic acid, 1,25-dihydroxyvitamin D3 [1,25(OH)2D3], or thyroid hormone on apo accumulation in media of filter-grown cultures of Caco-2 cells. However, 1,25(OH)2D3 and thyroid hormone increased apo B, apo A-IV, and apo A-I mRNA concentrations, retinoic acid increased apo B mRNA concentrations alone, and all three reduced apo E mRNA concentrations. Ratios of edited to unedited apo B mRNA were unaffected. In conclusion, culture substratum importantly influences Caco-2 cell differentiation. Soluble factors that influence cellular differentiation may affect apo gene expression over and above effects mediated by the culture substratum.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1514622 TI - Insulin-regulated sorting of glucose transporters in 3T3-L1 adipocytes. AB - Two glucose transporters (GLUT-4 and GLUT-1) move from within the cell to the plasma membrane (PM) when 3T3-L1 adipocytes are stimulated with insulin. To study the sorting of these two molecules, vesicles containing GLUT-4 and GLUT-1 were immunoadsorbed from basal and insulin-treated cells. Two different vesicle populations were isolated as follows: 1) a compartment that contained the majority of intracellular GLUT-4 and GLUT-1 and 2) a subpopulation of vesicles containing 43% of the intracellular GLUT-4 that was highly insulin regulatable and that contained relatively low levels of GLUT-1. After incubation at 19 degrees C, basal glucose transport was slightly increased, whereas insulin dependent transport was blocked. Consistent with these observations, cell surface GLUT-1 levels were increased in the basal state, whereas insulin-dependent translocation of GLUT-4 to the PM was blocked at 19 degrees C. However, insulin dependent sorting of GLUT-4 within the intracellular compartment was still evident at 19 degrees C. These data indicate that GLUT-1 and GLUT-4 are heterogeneously distributed throughout the same intracellular compartment in 3T3 L1 adipocytes. Furthermore, we have uncoupled two distinct steps in the insulin dependent movement of GLUT-4 to the cell surface. These include movement of GLUT 4 out of its storage compartment and accumulation of GLUT-4 at the cell surface. Only the former step occurs in cells preincubated at 19 degrees C. PMID- 1514623 TI - Estimation of the rate of appearance in the non-steady state with a two compartment model. AB - A simple tracer-based method for calculating the rate of appearance of endogenous substances in the non-steady state, free from the inconsistencies of Steele's equation, is still lacking. This paper presents a method based on a two compartment model by which the rate of appearance can be calculated with only a modest increase in complexity over Steele's approach. An equation is developed where the rate of appearance is expressed as a sum of three terms: a steady-state term, a term for the first compartment, and a term for the second compartment. The formula employs three parameters and makes the relationship between rate of appearance and specific activity changes explicit. An equation is also provided for estimating the error of the method in each individual run. The algorithm can be implemented with a spreadsheet on a personal computer. Simulated and experimental data obtained by the hyperinsulinemic euglycemic glucose clamp technique were used as a test. The accuracy with which the time course of glucose production could be reconstructed was clearly better than that using Steele's equation. Marked negative values for endogenous glucose output were calculated with Steele's equation but not with the new method. The characteristics of generality, simplicity, and accuracy and the availability of an error estimate make this new method suitable for routine application to non-steady-state tracer analysis. PMID- 1514624 TI - Role of EDRF in splanchnic blood flow of normal and chronic portal hypertensive rats. AB - The role of endogenous endothelium-derived relaxing factor (EDRF) in splanchnic blood flow was assessed in normal and portal vein-stenosed rats (PSRs). Specific and maximal inhibition of EDRF was achieved by intravenous administration of NG nitro-L-arginine (L-NOARG) as a 1.75 mumol/kg bolus, followed by constant infusion of 1.75 mumol/kg for 20 min. Pretreatment with L-arginine (175 mumol/kg iv) completely blocked both hypertension and the reduction in blood flow induced by L-NOARG. Pretreatment with D-arginine (175 mumol/kg iv) and prazosin (500 micrograms/kg iv) did not attenuate the pressor effect of L-NOARG. These results indicate that L-NOARG selectively blocks EDRF. The blood flow to the stomach, duodenum, jejunum, ileum, cecum, and colon in control rats was 81.1 +/- 8.7, 199.1 +/- 21.9, 153.3 +/- 20.0, 68.6 +/- 10.6, 79.4 +/- 11.8, and 59.3 +/- 7.8 ml.min-1.100 g-1, respectively, and in PSRs was 141.4 +/- 10.8, 244.0 +/- 10.4, 208.3 +/- 9.8, 126.8 +/- 13.0, 166.9 +/- 16.5, and 94.8 +/- 4.7 ml.min-1.100 g-1, respectively. Blood flow was measured using the radioactive microsphere method. L NOARG significantly reduced blood flow to the stomach, duodenum, jejunum, ileum, cecum, and colon in control rats by 47, 44, 48, 55, 40, and 41%, respectively, and in PSRs by 30, 27, 36, 33, 28, and 23%, respectively. The magnitude of blood flow reduction in PSRs was lower than in normal rats. These results indicate that EDRF plays an important role in control of the splanchnic circulation, but its effect on the hyperdynamic circulation observed in PSRs is insignificant. PMID- 1514625 TI - Effect of aspirin on ulcer site blood flow in cat stomachs. AB - Radioactive microspheres were used to measure blood flow in the cat stomach during exposure to saline, 0.075 M HCl, and then 15 and 30 min after exposure to 20 or 40 mM aspirin in HCl. At the end of the experiment, the stomach wall was divided into ulcerated regions and adjacent nonulcerated areas. When exposed to saline, both regions had similar blood flow: 27 +/- 5 and 25 +/- 5 ml.min-1.100 g 1 (means +/- SE). Addition of acid caused a significant increase in blood flow to 41 +/- 7 ml.min-1.100 g-1 only at those sites that eventually ulcerated in the presence of aspirin. In the adjacent nonulcerated regions, blood flow was 31 +/- 5 ml.min-1.100 g-1 and was not significantly greater than the flow recorded during saline exposure. Aspirin caused ulcer site blood flow to increase dramatically to 89 +/- 12 and 122 +/- 18 ml.min-1.100 g-1 after 15 and 30 min, whereas the adjacent nonulcerated tissue rose to 40 +/- 6 and 44 +/- 5 ml.min 1.100 g-1, respectively. The ulcer site hyperemia with acid alone suggests higher mucosal permeability in these regions allowing back-diffusion of acid and injurious agents. The present data obtained in the cat do not support the notion that ischemia plays a role in initiating nonsteroidal anti-inflammatory drug (NSAID)-induced ulcers, but rather that acute NSAID ulcers are associated initially with a hyperemia. PMID- 1514626 TI - Innervation of pylorus in control of motility and gastric emptying. AB - The motility index (MI) and contractile frequency were determined for the gastric antrum, pylorus, and duodenum during digestive and interdigestive states in eight dogs before and after resection of the ramus pyloricus nervi vagi (NR) and after selective proximal vagotomy (SPV) subsequent to NR. Neither NR nor subsequent SPV altered the migrating motor complex in the interdigestive state. In the digestive state, NR decreased the MI in the antrum, pylorus, and duodenum. The MI did not further change after SPV subsequent to NR. The cholecystokinin antagonist L364,718 decreased MI in the antrum, pylorus, and duodenum. After NR, L364,718 caused a further reduction in the MI during administration. Gastric emptying was accelerated after NR. SPV subsequent to NR increased gastric emptying further. L364,718, in the absence of NR, accelerated gastric emptying but only during the initial period of emptying. After NR, L364,718 also decreased the time required for emptying of 50 and 100% of the meal. After SPV subsequent to NR, no additional acceleration of emptying occurred. PMID- 1514627 TI - Polyamine transport systems in isolated rat hepatocytes derived from resting and regenerating livers. AB - Polyamines and their principal metabolite, gamma-aminobutyric acid (GABA), modulate eukaryotic cell growth. To determine whether the liver possesses specific polyamine transport sites and whether changes occur to these or GABA transport sites during hepatic regeneration, suspensions of rat hepatocytes derived from in situ collagenase perfusions of livers at times 0, 24, 48, and 72 h post-partial hepatectomy were incubated at 4, 20, and 37 degrees C with various concentrations of the following ligands: [3H]putrescine, [3H]spermidine, [14C]spermine, and [3H]GABA together with or without excess unlabeled ligand, KCN, ouabain, or digitoxigenin. Of the ligands studied, only [14C]spermine and [3H]GABA were associated with specific binding to hepatocytes derived from nonregenerating livers. Spermine binding correlated with the concentration of hepatocytes in the incubation mixture and reached equilibrium within 60 min. The approximate affinity constant (KD) was 5.5 x 10(-5) mol/10(6) hepatocytes, and maximum number of binding sites (Bmax) was 1.8 +/- 1.2 x 10(-7) mol.10(6) hepatocytes-1.min-1. Binding was neither temperature nor sodium dependent and was not inhibited by KCN, ouabain, digitoxigenin, other polyamines, or GABA. Aside from a 43% decrease in spermine binding at 24 h post-partial hepatectomy [5.1 +/- 1.1 vs. 8.9 +/- 3.1 x 10(3) disintegrations per minute (dpm)/10(6) hepatocytes at time 0, P less than 0.05] and a 39% decrease in GABA binding (3.4 +/- 1.3 vs. 5.5 +/- 1.9 x 10(3) dpm/10(6) hepatocytes, P less than 0.05), there were no significant changes in ligand binding during hepatic regeneration.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1514628 TI - Immunocytochemical studies suggest two pathways for enteroendocrine cell differentiation in the colon. AB - Enteroendocrine cells represent the most heterogeneous population of terminally differentiated cells in the mouse intestinal epithelium. Each of the approximately 15 different enteroendocrine cell subpopulations shows characteristic distributions along both the cephalocaudal and crypt-to-villus (in the small intestine) or crypt-to-surface epithelial cuff (in the colon) axes of the gut. These cells provide a sensitive model for studying how the continuously renewing gut epithelium is able to establish and maintain its spatial differentiation. Enteroendocrine cells are derived from the same multipotent stem cell that gives rise to enterocytes and goblet and Paneth cells. Regional differences in enteroendocrine cell number and type reflect positional differences in the differentiation programs of this lineage. To better understand the nature of these programs, we used multilabel immunocytochemical methods to examine the accumulation of endogenous neuroendocrine products as well as the product of a liver fatty acid binding protein/human growth hormone transgene in enteroendocrine cells located in proximal colonic glands. The results suggest that serotonin, substance P-, glucagon-like peptide-1 (GLP-1)-, peptide tyrosine tyrosine (PYY)-, neurotensin-, and cholecystokinin (CCK)-producing cells can all arise from a single stem cell located within a given gland. Based on pairwise comparison of the coexpression of each of these six products in individual cells as well as their ability to support transgene expression, it appears that the enteroendocrine lineage has two branches; one branch produces substance P and serotonin cells while the other yields GLP-1, PYY, neurotensin, and CCK cells. PMID- 1514629 TI - Cardiac performance in the portal vein-stenosed rat. AB - Patient studies and experimental models suggest that impaired cardiac function might contribute to the altered pressor responses and compromised reflex responses to hypotension observed in liver disease. To elucidate the role that portosystemic shunting plays in cardiac impairment, right atrial chronotropic and right ventricular inotropic responses to a beta-adrenoceptor agonist were compared using isolated cardiac tissues from sham-operated and chronic portal vein-stenosed rats. Maximal chronotropic responses of sinoatrial tissue from portal vein-stenosed rats to isoproterenol were reduced 18% (P less than 0.05) with no change in sensitivity [mean effective dose (ED50)]. Basal indexes of contraction were diminished 48% (P less than 0.0025) and 60% (P less than 0.0005) for developed tension and change in force over change in time (dF/dt), respectively, in ventricular tissue from portal vein-stenosed animals. In addition, the maximal response for isoproterenol-induced ventricular contraction was smaller in portal hypertensive animals (-44%, P less than 0.0005, and -52%, P less than 0.01 for developed tension and dF/dt, respectively), but no changes in isoproterenol ED50 values were found. These results indicate that portal venous hypertension with extensive portosystemic shunting leads to impairment of basal myocardial contraction and decreased chronotropic and inotropic responsiveness to beta-adrenoceptor agonists. PMID- 1514630 TI - Regulation of gene expression in gastric epithelial cell populations of fetal, neonatal, and adult transgenic mice. AB - Little is known about lineage relationships and differentiation programs of various epithelial cells present in mouse gastric units. We have previously used rat liver fatty acid binding protein/human growth hormone (L-FABP/hGH) transgenes to define epithelial cell lineages relationships in the small intestine of fetal and adult mice and to examine regulation of their terminal differentiation programs along the crypt-to-villus and duodenal-to-ileal axes. We have now used these transgenes to explore similar issues in the stomach. Immunocytochemical studies of fetal and adult transgenic L-FABP/hGH animals and their normal littermates revealed that the intact endogenous mouse L-FABP gene (Fabpl) is not expressed in gastric epithelium. Nucleotides-596 to +21 of the rat L-FABP gene direct "inappropriate" expression of hGH in the gastric epithelium as early as fetal day 15. From 1 to 13 mo, L-FABP-596 to +21/hGH expression occurs only in surface mucous cells of zymogenic and mucous gastric units; the reporter is not detectable in the enteroendocrine, parietal and chief cell populations of zymogenic glands. Electron microscopic immunocytochemistry revealed that hGH is directed to apical secretory granules in surface and pit mucous cells expressing the transgene. hGH levels vary widely among surface mucous cells both within single pits and between gastric units in a given animal. The heterogeneity noted in reporter expression suggests that there are marked differences in the regulatory environments of individual cells of a single type within a given gastric unit. This raises the possibility that cell differentiation programs in the stomach may not be as tightly coupled to cellular translocation as in the small intestine. Finally, the lack of expression of L-FABP-596 to +21/hGH in gastrin- and serotonin-immunoreactive cells of the stomach contrasts with its efficient expression in comparable cell types located in the duodenum; providing a model system for examining differential regulation of gene expression in terminally differentiated cell types represented in both gastric and intestinal epithelium. PMID- 1514631 TI - Changes in antroduodenal resistance induced by Cisapride in conscious dogs. AB - The effects of Cisapride on gastric outflow/pressure relationships have been examined in conscious dogs. In the digestive state, after inhibition of emptying in the first 10 min, Cisapride accelerated gastric emptying for 110 min by increasing the volume (7.3 +/- 1.2 vs. 2.3 +/- 0.3 ml) rather than by decreasing the interval between flow pulses (4.9 +/- 0.2 vs. 4.5 +/- 0.1s). After non nutrient gastric loading, Cisapride also first inhibited and then accelerated gastric emptying as the consequence of both a larger stroke volume (8.0 +/- 1.7 vs. 3.2 +/- 0.5 ml) and more frequent pulses (3.9 +/- 0.1 vs. 4.9 +/- 0.1 s). In both situations, Cisapride increased the amplitude of the antral/pyloric pressure waves. Antropyloroduodenal resistance increased substantially in the first 10 min after Cisapride then recovered to its control value. We conclude that stimulation of antropyloroduodenal motility by Cisapride can both impede and increase gastric emptying by changes in antroduodenal resistance. PMID- 1514632 TI - Capsaicin-induced hyperemia in the stomach: possible contribution of mast cells. AB - Topical application of capsaicin to the gastric mucosa results in marked hyperemia as a consequence of the release of vasoactive neuropeptides from sensory afferent neurons. Because many of these neuropeptides have the capacity to induce mast cell degranulation, we investigated the possible contribution of mast cells to capsaicin-induced hyperemia. Application of capsaicin to the gastric mucosa of normal rats resulted in a concentration-dependent increase in blood flow. In rats in which mastocytosis was induced by prior infection with Nippostrongylus brasiliensis, the hyperemic responses to capsaicin were significantly greater than in control rats. This augmented hyperemic response could be significantly attenuated by pretreatment with a histamine H1-receptor antagonist (pyrilamine) or with a mast cell stabilizer (doxantrazole). Depletion of mucosal mast cells through treatment with dexamethasone also significantly reduced the hyperemic response to capsaicin. Hyperemic response to capsaicin in normal rats and in rats with mucosal mastocytosis could be completely abolished by pretreatment with ruthenium red or prior ablation of the sensory afferent neurons with capsaicin. These results suggest that in rats with gastric mastocytosis, sensory neuron-dependent activation of mast cells contributes to the hyperemic response to topical capsaicin. These findings are therefore consistent with the hypothesis that there is communication between nerves and mast cells in the gastric mucosa, at least in rats previously infected with N. brasiliensis. PMID- 1514633 TI - Differential regulation of cytochrome P-450 genes along rat intestinal crypt villus axis. AB - Mammalian small intestine contains cytochrome P-450-dependent monooxygenase enzymes that are capable of metabolizing a wide variety of xenobiotics and activating procarcinogens to mutagenic compounds. The epithelial cells lining the small intestine are separated into a proliferating undifferentiated compartment located in crypts and a nonproliferating differentiated compartment located on villi. The constitutive expression and induction by xenobiotics of genes that encode components of the cytochrome P-450-dependent mono-oxygenase system along the rat intestinal crypt-villus axis were investigated using isolated epithelial cells and in situ hybridization. For each gene examined, hybridization analysis of RNA obtained from isolated epithelial cells correlated with findings on in situ RNA hybridization. Cytochrome P-450IA1 mRNA (CYP1A1), the major aromatic hydrocarbon-inducible P-450, and cytochrome P-450IIB1 mRNA (CYP2B1), the major phenobarbital-inducible P-450, were constitutively expressed in villus cells with no detectable mRNA present in crypts. Treatment with several chemical inducers resulted in a marked increase in CYP1A1 mRNA in both crypt and villus cells. In contrast, although CYP2B1 mRNA was inducible in villus cells, CYP2B1 mRNA was not detected in crypts after treatment with chemical inducers. NADPH cytochrome P-450 reductase, a necessary component for the activity of all P-450 enzymes, was expressed constitutively at low levels only in villus cells. Treatment with dexamethasone induced reductase mRNA in both crypt and villus cells. Taken together, these results demonstrate that there is a complex gene-specific pattern of expression of the microsomal monooxygenase system along the crypt-villus axis of rat small intestine.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1514635 TI - Measurement of axial forces during emptying from the human stomach. AB - Our aim was to measure axial forces in the stomach and to evaluate their relation to circumferential contractions of the gastric walls and the emptying of gastric content. We used a combination of simultaneous radioscintigraphy, gastroduodenal manometry, and an axial force transducer with an inflatable 2-ml balloon fluoroscopically placed in the antrum. In vitro studies demonstrated that the axial force transducer records only antegrade forces along the longitudinal axis of this probe in an intensity-dependent manner. In vivo studies were performed in five healthy subjects for at least 3 h after ingestion of radiolabeled meals. When administered separately, the emptying of liquids or solids from the stomach is associated with generation of antral axial forces and coincident phasic pressure activity; however, almost 20% (average) of gastric axial forces during emptying of liquids or solids are unassociated with proximal or distal antral pressure activity ("isolated" forces). High amplitude antral axial forces and pressures occur during both lag and postlag emptying phases. During emptying of liquids, there is a trend for axial forces to be coincident more often with proximal than with distal antral pressure activity and vice versa for the emptying of solids (P = 0.015). These data suggest that when placed in the antrum, the transducer can semiquantitatively record axial forces during gastric emptying. By combining these observations with the data from in vitro studies, it appears that axial forces predominantly result from traction on the balloon by the longitudinal vector resulting from circumferential gastric contractions. The combination of radioscintigraphy and measurement of antral axial forces is a promising method to evaluate mechanical forces involved in the emptying of the human stomach. PMID- 1514634 TI - Polyamines attenuate jejunal mucosal injury induced by oleic acid. AB - Effects of putrescine, spermidine, and spermine on lipid-induced injury to jejunal mucosa were assessed in anesthetized rats. Mucosal epithelial integrity was continuously monitored by measuring blood-to-lumen clearance of 51Cr-labeled EDTA. Perfusion of jejunal lumen with emulsified lipid (20 mM sodium taurocholate and 40 mM oleic acid) increased 51Cr-EDTA clearance. Addition of spermidine (0.5 mM), but not putrescine (2.0 mM) or spermine (0.25 mM), to the lipid perfusate reduced the increment in 51Cr-EDTA clearance. Histological evaluation of jejunal mucosa indicated that the epithelial lining of the villous tips was damaged by emulsified oleic acid and that this injury was ameliorated by spermidine. Pretreatment of jejunal mucosa with spermidine did not prevent disruption of mucosal integrity induced by a subsequent perfusion with emulsified lipids. Intravenous infusion of spermidine to achieve an extracellular concentration of 0.5 mM did not prevent the lipid-induced increase in 51Cr-EDTA. Spermidine also ameliorated lipid-induced disruption of Caco-2 cell monolayers in culture; this protective effect was dose dependent and was observed only when spermidine was applied to the apical aspect of the monolayers. These findings indicate that spermidine must be present on the apical portion of the epithelial cell during lipid insult. Substitution of lysine or arginine for spermidine did not reduce the extent of lipid-induced injury to jejunal mucosa, indicating that spermidine's protective effects cannot simply be attributed to its cationic nature. Spermidine did not alter the turbidity of a micellar oleic acid solution, indicating that spermidine was not removing oleic acid from the soluble phase.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1514636 TI - Preservation and propagation of cyclic myoelectric activity after feeding in rat small intestine. AB - The cyclic nature and distal propagation of the fasting migrating motor complex (MMC) of the small intestine have been well described. The fate of the MMC after feeding, however, has not been elucidated. We used time series analysis with fast Fourier transforms (FFT) to study myoelectric cycling before and after feeding. Ten rats were chronically prepared with bipolar electrodes secured to the duodenum and proximal jejunum. Spikeburst frequency was recorded before and after feeding simple nutrients. During fasting, cyclic activity occurred at the MMC frequency. Although after feeding this periodicity appeared disrupted, FFT analysis showed persistent cycling at the fasted (MMC) rate. Digital filtering of data at the MMC frequency isolated cycling from background noise during both fasted and fed states and showed a depression in the amplitude of the waveform after feeding. Root-mean-square analysis of the waveform confirmed statistically significant depression of amplitude by 47-57%. The waveform propagated from the duodenum to the jejunum during both the fasted and fed state at an unchanged rate. We conclude that factors controlling myoelectric cycling during the fasted state persist after feeding, allowing continued net abroad propulsion of food. PMID- 1514637 TI - Influence of luminal nutrient composition on hemodynamics and oxygenation in developing intestine. AB - Age-related differences in the intestinal hemodynamic and oxygenation responses to carbohydrate, protein, and lipid were studied in 1-day-, 3-day-, 2-wk-, and 1 mo-old piglets. A branch of the mesenteric vein draining an isolated loop of jejunoileum was used to measure intestinal blood flow, arteriovenous oxygen content difference, and venous and capillary pressure and to calculate oxygen uptake and vascular resistance. Fractionated intestinal flow was measured with radiolabeled microspheres. Measurements were made before and after luminal placement of either 5% glucose, 2.3% casec, or 5% corn oil. In 1-day-old animals, unlike all older age groups, total intestinal blood flow and vascular resistance were unchanged by any nutrient. Fractionated flow to the mucosa/submucosa levels did, however, increase in the intestine of 1-day-old piglets to a similar extent as that in older age groups. Placement of lipid or protein into the lumen led to increased oxygen uptake in all age groups, whereas carbohydrate absorption resulted in no increase in intestinal oxygen consumption in 1- and 3-day-old animals. In 1-day-olds, the increased oxygen consumption was achieved by enhanced oxygen extraction with no change in total blood flow, whereas all other groups demonstrated increases in blood flow and/or oxygen extraction. Compared with a mixed meal, oxygen consumption was not significantly greater for an individual nutrient component. PMID- 1514638 TI - Two-dimensional coupling by gap junctions in cultured gastric smooth muscle monolayers. AB - We studied intercellular transfer in cultured rabbit gastric smooth muscle cell monolayers after microinjection of electrotonic current or the fluorescent probe Lucifer yellow CH. Because cultured gastric muscle cells proliferate in vitro and form regular arrays of parallel spindle-shaped cells, we sought to assess the role of cell shape and orientation in determining two-dimensional coupling properties. With the use of electron microscopy, gap junctions were identified between adjacent cells. Northern blot analyses using specific cDNA probes demonstrated expression of mRNA for the gap junction protein connexin43. Dye injection of Lucifer yellow resulted in 97% transfer to at least one adjacent cell, and 88% of adjacent cells received dye. Electrophysiological studies were performed using two intracellular microelectrodes to measure electrotonic current flow between cells at varying interelectrode distances. Current flow in the monolayers was modeled using a modified two-dimensional analysis. Initial assessment showed that the ratio of calculated space constants (longitudinal axis/perpendicular axis) was 4.4, indicating anisotropic conditions. However, when a geometric transform was used to normalize the spindle-shaped cells to regular hexagons, the space constants became statistically equivalent (200 microns longitudinal, 256 microns perpendicular). These results suggest that anisotropy of current flow in the monolayer of gastric smooth muscle cells was due primarily to the shape of the cells and not to intrinsic membrane properties or the distribution of gap junctions. PMID- 1514639 TI - Surfactant protein C: a review of its unique properties and metabolism. AB - Traditionally, our thinking about surfactant proteins has centered around their effects on the biophysical properties of surfactant phospholipids. It is now apparent that the three major surfactant proteins (SP-A, SP-B, and SP-C) are a biochemically and functionally diverse group of mammalian peptides. Accumulated data suggest that they have roles beyond modulation of alveolar surface tension. SP-C is a 33-35 amino acid peptide found in organic extracts of pulmonary surfactant. In part, because of its extreme hydrophobicity, a full understanding of SP-C is presently incomplete. Progress to date has included evaluation of the biophysical properties and investigations of the SP-C gene, including studies of the SP-C promoter. This review describes the unique structural and functional properties of the SP-C molecule and summarizes available data on its molecular biology and metabolism. Studies from literature show that SP-C represents a physiologically important peptide with novel structural properties; namely, extreme hydrophobicity, an alpha-helical membrane spanning region, and a unique posttranslational modification: palmitoylation. From data on similarly modified proteins, we propose that the properties of SP-C, including the covalent addition of palmitic acid, render it capable of being targeted to and interacting with specific cell membranes. A complete understanding of SP-C, especially with regard to its metabolism and function, may require a reorientation of our thinking to consider SP-C as a membrane peptide and not just as a "surfactant protein." PMID- 1514640 TI - Cigarette smoke-induced airway goblet cell secretion: dose-dependent differential nerve activation. AB - We studied the effect of acute inhalation of middle-tar cigarette smoke on airway goblet cell secretion in anesthetized guinea pigs. Secretion induced by a low dose of smoke (10 breaths diluted 1:10 in air) was blocked by either hexamethonium or by filtering out the particulate phase of the smoke. The response was partially inhibited by atropine but was not inhibited by propranolol, phentolamine, or capsaicin pretreatment. Cutting the nerve supply to the airways did not inhibit the response to low-dose smoke. In contrast, goblet cell secretion induced by a high dose of cigarette smoke (20 breaths undiluted) was inhibited by capsaicin pretreatment but not by autonomic receptor blockade nor by filtering out the particulate phase. Secretion induced by the vapor phase of the high dose of cigarette smoke was blocked by capsaicin pretreatment but was not inhibited by hexamethonium. We conclude that in guinea pig airways the particulate phase of low doses of smoke activates cholinergic nerves via stimulation of parasympathetic ganglia, whereas the vapor phase of high doses of smoke activates capsaicin-sensitive sensory nerves. PMID- 1514641 TI - Prostaglandin D2 production and identification of prostaglandin H synthase within canine mast cell granule. AB - We have identified the presence of functional prostaglandin H synthase (PGH synthase, E.C. 1.14.99.1, or cyclooxygenase) within canine mast cell granules by demonstrating the generation of prostaglandin (PG) D2 from isolated and purified granules incubated with substrate as arachidonic acid or stimulated with calcium ionophore, A23187. This confirms the presence of both enzyme and substrate within the granule. Localization of PGH synthase to the granule was confirmed by immunoblotting of the pure granule preparation and by immunocytochemistry using the whole cell. In functional studies, colchicine, a microtubule polymerization inhibitor, caused a fall of up to 70%, both in the amount of histamine released and in the amount of PGD2 generated. This suggests either that functional PGH synthase is closely associated and coactivated with granules or that there is an independent association of this enzyme with the microtubule system. Release of the preformed and newly formed mediators of the mast cell appear to be closely linked, and prevention of degranulation may therefore attenuate the effects of both classes of mediators. PMID- 1514642 TI - Structural and functional impairment of surfactant protein A after exposure to nitrogen dioxide in rats. AB - The major surfactant protein A (SP-A) determines the dynamics of surfactant metabolism and function. We now for the first time studied the in vivo exposure of the SP-A to nitrogen dioxide (NO2) and compared it to in vitro exposure effects. Several properties that are believed to possess physiological functions were investigated. Exposure of rat SP-A to NO2 showed 1) a higher alveolar pool size after in vivo exposure, 2) a slightly decreased mannose binding capacity for the in vivo exposed form but a highly decreased binding after in vitro exposure, 3) an affected protein-lipid aggregation that was impaired most by the in vitro exposed protein, 4) a low inhibition for the secretion of phosphatidylcholine in isolated type II pneumocytes, and 5) no difference in apparent molecular weight and immunological reactivity of the differently exposed SP-A. The NO2-induced alterations of the SP-A may contribute to the pulmonary toxicity of this oxidant. It is clear from this study that the extend of the effects from in vivo and in vitro exposure are different. Therefore both forms of exposure are necessary to assess the biological significance of NO2 exposure. PMID- 1514643 TI - Spontaneous production of PDGF A-chain homodimer by rat lung fibroblasts in vitro. AB - Platelet-derived growth factor (PDGF) is considered a decisive mediator of fibroblast growth and phenotype within the lung. The cellular sources of PDGF within the lung remain undefined. The ability of lung fibroblasts themselves to produce PDGF in vitro was therefore investigated. Northern and Western blot analyses revealed the expression of PDGF-A mRNA and secretion of A-chain containing proteins by fibroblasts derived from adult and fetal rat lung. PDGF-A gene or protein expression were below the limits of detection in two human lung fibroblast lines examined in a similar manner. PDGF-B transcripts or proteins were not detected in any lung fibroblast line examined. Conditioned medium (CM) was collected from these same lung fibroblast lines and tested for its ability to promote cell growth using human fetal lung fibroblasts as targets. Both adult and fetal rat lung fibroblasts were found to produce a potent and efficacious stimulus for cell growth. Growth-promoting activity in rat fibroblast-derived CM functioned as a "competence" factor and was partially inhibited by anti-PDGF antibody. Thus rat lung fibroblasts in vitro produce potent growth factors of which at least one appears to be PDGF-AA. Differences in the expression of PDGF AA between rat and human lung fibroblasts exist. Growth factor-producing fibroblasts may play a role in lung repair and remodeling through production PDGF AA in vivo. PMID- 1514644 TI - L-arginine restores endothelium-dependent relaxation in pulmonary circulation of chronically hypoxic rats. AB - We investigated whether loss of endothelial-derived relaxing factor (EDRF) activity in the pulmonary vessels of chronically hypoxic rats could be restored by pretreatment with L-arginine. We measured vasodilation to acetylcholine (ACh), calcium ionophore A23187, or linsidomine (Sin-1) under conditions of increased vascular tone induced by U-46619 (50 pmol/min), as well as vasoconstriction to endothelin-1 (ET) in isolated lungs pretreated with meclofenamate (3 microM). In lungs from normoxic (N) rats, in vitro L- or D-arginine (10(-3) M) did not alter vasodilation to the endothelium-dependent agents ACh (10(-9)-10(-6) M) and A23187 (10(-9)-10(-7) M), but NG-monomethyl-L-arginine (10(-3) M) completely abolished it. In lungs from rats exposed to 3 wk of hypoxia (H), vasodilation to ACh or A23187 was fully restored after in vitro L-arginine (10(-3) M) or N alpha-benzoyl L-arginine (5 x 10(-5) M) but remained abolished after D-arginine, L-citrulline, L-ornithine, or L-argininosuccinic acid. In vivo pretreatment of H rats with L arginine (300 mg/kg iv) 30 min before isolating the lung also restored vasodilation to A23187. Vasodilation to the endothelium-independent agent Sin-1 was similar in both groups of lungs and was not altered by in vitro L-arginine. L arginine attenuated the increased pressor response to ET (300 pmol) of H rat lungs but had no effect in N rats. Our results demonstrate that loss of EDRF activity associated with hypoxic pulmonary hypertension may be reversed by supplying L-arginine. PMID- 1514645 TI - Localization of alveolar surfactant clearance in rabbit lung cells. AB - Localization of surfactant phospholipid clearance in lung cells was investigated in vivo in rabbits using radiolabeled dipalmitoylphosphatidylcholine (DPPC) and 1,2-dihexa-decyl-sn-glycero-3-phosphocholine (DPPC-ether), a phospholipase A1- and A2-resistant analogue of DPPC. After intratracheal injection of liposomes of the labeled lipids associated with unlabeled surfactant, adult rabbits were killed in groups of three to five at 0, 4, 12, and 24 h with recovery of bronchoalveolar lavages for alveolar macrophages and surfactant. Type II cells and tissue-associated macrophages were isolated on Percoll gradients following elastase and trypsin digestion of the lungs. Radiolabel recoveries as saturated phosphatidylcholine were measured in alveolar wash, alveolar macrophages, lung tissue, and the type II cell and mixed cell bands from the Percoll gradients. Cost accounting of label demonstrated similar recoveries at 0 h, but significantly more DPPC-ether compared with DPPC in cells at later times, indicating ineffective degradation of the DPPC-ether. Internalization of the lung tissue-associated labels into cells was time dependent. At all times, greater than 65% of the cell-associated labels were recovered in type II cells, indicating the primary role for these cells in clearing alveolar surfactant phospholipid in vivo. The total contribution of alveolar macrophages to the overall clearance was approximately 20%. PMID- 1514646 TI - Pulmonary SP-A enhances adsorption and appears to induce surface sorting of lipid extract surfactant. AB - The effect of surfactant concentration and supplementation with surfactant associated protein A (SP-A) on the surface activity of lipid extract surfactant (LES) was examined using a captive bubble technique. Adsorption of LES is strongly concentration dependent over the range of 50-1,000 micrograms/ml. Addition of SP-A to LES at low concentrations in the presence of calcium dramatically increases the rate of adsorption. In quasistatic cycling experiments, samples containing SP-A require less compression to achieve low surface tensions even during the first compression cycle. Calculated film compressibilities at 15 mN/m indicate that SP-A alters the surfactant monolayer behavior such that in a small number of cycles the compressibility is indistinguishable from that of pure DPPC. Furthermore, SP-A reduces the incidence of bubble "clicking," suggesting a stabilization of the monolayer at low surface tensions. In dynamic cycling experiments, SP-A reduces compression of the film area required to achieve a low surface tension of approximately 1 mN/m. SP-A eliminated the plateau just below 25 mN/m normally observed during the compression phase with low concentrations of LES and the shoulder observed at approximately 35 mN/m during expansion. In the presence of SP-A and, to a lesser extent with high concentrations of LES, there is a marked lag in the increase in surface tension during the initial part of the dynamic expansion loop, with surface tensions remaining near 1 mN/m for approximately 10% of the increase in bubble area. The results indicate that SP-A enhances phospholipid adsorption during dynamic cycling and may enhance elimination of non-DPPC lipids during cycling.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1514647 TI - Time course of thrombin-induced increase in endothelial permeability: relationship to Ca2+i and inositol polyphosphates. AB - The temporal relationship between the alpha-thrombin-induced increase in transendothelial permeability and the alpha-thrombin-mediated changes in several key transmembrane signaling events was examined in confluent monolayers of bovine pulmonary artery endothelial cells (BPAEC). The time courses of inositol 1,4,5 trisphosphate [Ins(1,4,5)P3] generation, changes in cytosolic [Ca2+] ([Ca2+]i), and reorganization of cytoskeletal F-actin were determined to assess the relationship between these events and the onset of the alpha-thrombin-induced increase in endothelial permeability. alpha-Thrombin (10(-7) M) increased the transendothelial 125I-albumin clearance rate half-maximally by approximately 1 min and maximally by approximately 2 min (160% over control level). The increase in permeability occurred concomitantly with reorganization of F-actin cytoskeleton (i.e., loss of peripheral band and increased stress fiber density) and increased actin polymerization. Stimulation of fura-2-loaded BPAEC with 10( 7) M alpha-thrombin produced a typical biphasic rise in [Ca2+]i. The initial rapid increase in [Ca2+]i peaked by approximately 16 s after thrombin challenge and the [Ca2+]i response showed a slow decrease to half-maximal within 50 s. The alpha-thrombin-induced increase in permeability as well as the increase in [Ca2+]i were consistently preceded by increased Ins(1,4,5)P3 generation detectable within 10 s after thrombin challenge. These results indicate that alpha-thrombin triggers a cascade of events (i.e., Ins(1,4,5)P3 generation and the ensuing rise in [Ca2+]i), which may comprise the second messengers that mediate F-actin reorganization and the increase in endothelial permeability. PMID- 1514648 TI - Filter paper equilibration as a novel technique for in vitro studies of the composition of airway surface fluid. AB - We describe techniques which we developed to study the composition and regulation of airway surface fluid (ASF). ASF from isolated equine tracheal mucosa was absorbed onto or equilibrated with small strips of ashless filter paper after timed incubations in a water-saturated, 37 degrees C environment. After expression of the fluid from the paper, constant-volume aliquots of the samples were pipetted with a microvolumetric pipette on a filmed grid, together with standards containing known concentrations for Na, Cl, K, Ca, S, and P. Analysis of the microdroplets by dispersive X-ray microanalysis on a scanning electron microscope demonstrated that ASF from "unstimulated" tracheal tissue is significantly altered compared with the Ringer solution which was used to rinse the mucosal surface before incubation, in that Na is significantly decreased (approximately 130 mM), whereas K is significantly increased (approximately 16 mM). Furthermore, when a beta-adrenergic agonist (isoproterenol 10(-4) M) was added to the serosal surface, the Na concentration significantly increased to values which approached Ringer solution (146 +/- 5.3 mM) and were significantly different compared with the Na values obtained in unstimulated tissues. In contrast, Na remained unchanged after addition of a cholinergic agonist (metacholine, 10(-4) M) to the serosal side of the tissue; however, as with beta adrenergic stimulation, most other minor elements and especially K significantly decreased compared with their values in unstimulated tissue. These results clearly suggest that ASF composition is clearly controlled by active transport of the airway epithelium and may be influenced by neurohumoral stimulation. PMID- 1514649 TI - Influences of endogenous and exogenous TGF-beta on elastin in rat lung fibroblasts and aortic smooth muscle cells. AB - The factors that regulate elastin production during neonatal lung development have not been elucidated. Previous investigations suggested that transforming growth factor-beta (TGF-beta) increases elastin production by neonatal rat lung fibroblasts (LF). We examined whether this effect of TGF-beta was unique to these cells or was evident in other neonatal cells, which constitutively produce elastin, or in cells from adults, whose constitutive elastin production is low. We have quantitated soluble elastin, elastin mRNA, and TGF-beta production in primary cultures of smooth muscle cells (SMC) and LF from neonatal and adult rats and have examined the alterations in soluble elastin and elastin mRNA that result from adding 100 pM exogenous TGF-beta 1 to these cultures. Unsupplemented cultures of LF and SMC obtained from neonatal rats exhibited higher steady-state levels of elastin mRNA and contained more soluble elastin in their culture medium than did cells from adult animals. When neonatal LF were supplemented with 100 pM TGF-beta 1, they showed a significant increase in the soluble elastin content of their culture medium and their steady-state elastin mRNA. Neither LF obtained from adults nor SMC obtained from neonatal or adult rats significantly increased their soluble elastin or steady-state elastin mRNA after the addition of exogenous TGF-beta. When neonatal LF were supplemented with an anti-TGF-beta neutralizing antibody, the soluble elastin content of the culture medium decreased significantly. These data suggest that the responsiveness of elastin expression to TGF-beta is limited to neonatal LF and that endogenous TGF-beta influences elastin production by neonatal LF. PMID- 1514650 TI - Surfactant proteins and lipids are regulated independently during hyperoxia. AB - Adult hamsters were exposed to 100% oxygen for up to 8 days. At time of death lung tissue was analyzed for the expression of surfactant protein (SP) genes, and surfactant was isolated from alveolar lavage fluid. Surfactant was analyzed for the composition of proteins and phospholipids and for its surface properties. We found, over the 8 days of exposure, that an alveolitis composed of polymorphonuclear leukocytes (PMNs) and alveolar macrophages, accompanied by exudation of edema fluid, appeared in the alveolar spaces. The steady-state levels of SP mRNAs declined after 8 days of exposure to 100% oxygen, but the patterns indicated individual genetic control. SP-A was elevated early in the course of the hyperoxic exposure but decreased significantly by day 8; SP-B decreased continuously; SP-C was unchanged (or slightly elevated) through day 2 and then declined. The amounts of recoverable lavage surfactant increased by greater than threefold, and the phospholipid composition showed increasing percentages of disaturated phosphatidylcholine. All surfactants lowered surface tension to less than 10 dyn/cm, but the adsorption rates decreased as exposure progressed. The results indicate that lung injury induced by 100% oxygen is accompanied by altered patterns of surfactant metabolism, possibly because of a changing type II cell phenotype or alterations in Clara cell-derived surfactant. These changes may result in perturbed physiological function contributing to decreased lung compliance. PMID- 1514651 TI - Near-infrared spectroscopy in newborn infants. AB - Neonatal encephalopathy of early onset, plausibly related to hypoxia and ischemia remains one of the main problems in perinatal medicine. Efforts are necessary to find new non-invasive methods for assessing brain oxygenation. Near-infrared spectroscopy (NIRS) provides information on the concentrations of the oxygenated and reduced forms of hemoglobin, as well as the redox state of cytochrome aa3. Different important variables can be derived through hemoglobin measurement, such as cerebral blood volume and flow, and the responses of these to changes in pCO2. Changes in cytochrome aa3 may provide immediate information on intracellular oxygen utilization. Various studies have shown the feasibility of NIRS in preterm infants. Methodological and technical problems of this method are discussed. PMID- 1514652 TI - Bromide treatment of pharmaco-resistant epilepsies with generalized tonic-clonic seizures: a clinical study. AB - In a retrospective controlled clinical study we investigated the efficacy of bromides (BR) as to the frequency of generalized tonic-clonic seizures (GTCS) as a monotherapy (n = 5) or combined with other antiepileptic drugs (AEDs) (n = 55), and compared the results statistically with those achieved with a treatment based on phenobarbitone (PB) and/or phenytoin (PHT) in a very similar group of another 60 patients. All patients treated with BR had previously proved to be pharmaco resistant. In most of the cases the epilepsies were based on early cerebral lesions, and were partly associated with severe mental and physical handicaps. Most of the patients were between three and 14 years old. The percentage of responders was 58%, which means a reduction in the GTCS-frequency of more than 50%. The positive result was observed for 28 months on the average. 27% of all patients became free of GTCS for 18 months on the average (range, 44 days to 62 months), and 32% were improved (reduction in GTCS-frequency of more than 50% while not GTCS-free) for nearly three years on the average (range, 79 days to 110 months). Compared to PHT or PB, BR were slightly more efficient and similarly tolerable, but no statistically significant difference was seen (48% responders in the control group versus 58% responders in the BR-group). Thus, the statistical correlation with competitive therapies confirmed the good efficacy of BR against GTCS, which was previously demonstrated by clinical tests without control studies. We recommended BR in the case of every pharmaco-resistant epilepsy with GTCS as a therapeutic alternative. PMID- 1514653 TI - Occipital deep white matter hyperintensity as seen by MRI: 1. Clinical significance. AB - Magnetic resonance imaging was performed in 270 patients with various neurologic complaints (1-15Y) with a 0.5 tesla superconducting imaging system using a field echo T1-weighted sequence and spin echo T2-weighted and PD-weighted sequences. Twenty-seven of them had deep white matter hyperintensity (DWMH) in the occipital lobe on T2-weighted images. The frequency of mild DWMH differed in different age groups, suggesting that mild DWMH may result from delayed myelination in the central nervous system. However, the frequency of severe DWMH, which was revealed as isointense relative to cerebrospinal fluid, did not differ in different age groups and it was significantly more common in severely retarded patients. Classification of DWMH based on the signal intensity is valuable to distinguish white matter abnormalities in the occipital lobe from delayed myelination in the same site. PMID- 1514654 TI - Multimodality evoked potentials in severe athetoid cerebral palsy: correlation with clinical features and all-night polygraphical data. AB - We examined the correlation between the clinical and electrophysiological features, short latency somatosensory evoked potentials (SSEPs), auditory brainstem responses (ABRs), electrically elicited blink reflexes (BRs) and all night polysomnographical examination (PSG) data in eight patients with severe athetoid cerebral palsy (ACP). Absence ABRs were observed in cases who had suffered from severe neonatal hyperbilirubinemia (posticteric ACP), and in most of them gaze abnormalities and a significant reduction in rapid eye movements during REM sleep, as observed on PSG, coexisted. Prolongation of the interpeak latency, N13-N20, of SSEPs existed concurrently with disturbed late components of BRs in two cases of posticteric ACP. The phasic contractions of the submental muscle during sleep were impaired in most of the patients. Multimodality evoked potentials together with PSGs seem to be useful for assessing brainstem dysfunctions in ACP and might also be of use for elucidating the pathogenesis of the episodic sudden death in ACP. PMID- 1514655 TI - Usefulness of PET scan in a child with mesial frontal lobe epilepsy. AB - Positron emission tomography (PET) scan with 18F-fluorodeoxyglucose (18F-FDG) was performed in a 14-year-old boy who had seizures suspected to have originated in mesial frontal lobe. The seizures occurred in clusters and were characterised by a change in the facial expression at seizure onset and complex motor manifestations consisting of kicking, swaying and screaming. Ictal EEG showed rhythmic alpha-waves in the left frontal area association with the ictus. Cerebral CT, MRI and SPECT revealed nothing of significance, but the PET brain scans showed frontal and parietal hypometabolism, which was most prominent in the left mesial frontal lobe. The present case suggests that FDG-PET scanning may be useful for the diagnosis of the mesial frontal epilepsy, when other imaging studies fail to show abnormalities. PMID- 1514656 TI - A case of myasthenia gravis complicated with hyperthyroidism and thymic hyperplasia in childhood. AB - We report here a case of myasthenia gravis complicated with hyperthyroidism and thymic hyperplasia. The patient was a 13-year-old girl with struma and hyperthyroidism which began at age 12. Two weeks following the initiation of treatment against hyperthyroidism she developed left blepharoptosis, diplopia, and dysphagia, which responded promptly to edrophonium administration. An increase of the anti-acetylcholine receptor antibody was found in the serum. A chest CT showed a large soft tissue mass in front of the ascending aorta, which was proven histopathologically as thymic hyperplasia. The patient underwent an extensive thymectomy and was placed on combination therapy with an anti-thyroid drug, glucocorticosteroid, and an anti-cholinesterase drug. Her symptoms and signs have been well controlled by this treatment. Coexistence of myasthenia gravis, hyperthyroidism, and thymic hyperplasia in childhood have never been documented in literature. PMID- 1514657 TI - Infantile polymyositis: a case report. AB - A 10-month-old Japanese boy developed progressive muscle weakness and hypotonia at 3 months of age. Because of striking inflammatory cellular infiltration in his muscle biopsy, he was diagnosed as having infantile polymyositis and was placed on steroid and immunosuppressive medication when he was 10-month-old. His physical condition was not significantly altered, though serum creatine kinase (CK) level was normalized (1,500 iu/l----90 iu/l). These findings contrast with previous reports documenting improvement with steroid administration. PMID- 1514658 TI - Microgyric and necrotic cortical lesions in twin fetuses: original cerebral damage consecutive to twinning? AB - Extensive cortical necrosis associated with malformative microgyric-like lesions and with necrotic lesions of the white matter was observed in two male 25 week fetuses. These cases differed from previously reported cases of brain damage in monozygotic twins: both fetuses were affected and the lesions occurred early in pregnancy, before the end of neuronal migration, thus resulting in a cortical malformation associated with destructive lesions. PMID- 1514659 TI - Abnormal metabolism of carnitine and valproate in a case of acute encephalopathy during chronic valproate therapy. AB - We analyzed the urinary metabolic profiles of valproate (VPA) and carnitine metabolism in an epileptic patient who died of acute encephalopathy during VPA therapy. On admission, the serum free carnitine level was greatly decreased and gas chromatographic mass spectrometric analysis of organic acids in urine showed a complete lack of beta-oxidation metabolites of VPA, while omega-oxidation was markedly increased. After administration of L-carnitine, the levels of acylcarnitine in both serum and urine, and of serum free carnitine increased, and the metabolites of beta-oxidation appeared in urine, while there was no improvement in the liver and renal functions. This is not a typical case of VPA induced hepatotoxicity and the main cause of the disease is not clear. But the results show that the mitochondrial beta-oxidation of VPA was greatly disturbed in this patient, which may be related to the carnitine deficiency induced by the chronic VPA-therapy. PMID- 1514660 TI - The more unusual sleep disturbances of childhood. AB - The sleep patterns of children often cause anxiety to their parents. Some disturbances are unusual, and therefore may cause diagnostic difficulties. Sleep walking and night terrors can be confused with epileptic seizures. The sudden sleep of narcolepsy can lead to false accusations, when in fact the episodes are beyond the child's control. The associated phenomena of cataplexy, hypnogogic hallucinations and sleep paralysis can be particularly alarming, especially if they occur in the absence of narcolepsy. The overlap between narcolepsy and the Kleine-Levin syndrome is confirmed. Although of a different nature the sleep apnoea syndrome is equally important from the point of view of diagnosis and treatment. PMID- 1514661 TI - Electrophysiological study on hydranencephaly. AB - An electrophysiological study was performed on 2 children with hydranencephaly diagnosed by CT and/or MRI. Case 1 was a 4-month-old boy who had no rostral tissues above the midbrain. Case 2 was a 5-year-old boy in whom CT showed retention of the thalamus. Short latency somatosensory evoked potentials (SSEP) in both cases exhibited the absence of cortical activity (N1 and P4) with the preservation of waves of brain stem origin. However, in case 1, wave component No was not observed, while No was seen in case 2. It was postulated, thus, that the No component of SSEP on median nerve stimulation in children, which corresponds to N16 in adults, may originate in the thalamus. PMID- 1514662 TI - International consensus report on diagnosis and management of asthma. PMID- 1514663 TI - A comparative study of four different bronchial challenge tests. AB - The correlation between 4 commonly used tests for assessment of airway hyperresponsiveness was studied in 10 asthmatics by performing bronchial challenges with histamine, ultrasonically nebulised distilled water (UNDW), exercise, and a relevant allergen. All tests were performed within 4 weeks for each individual and at least 48 h apart. A significant correlation was found between histamine challenge and exercise challenge (r = -0.74). Other correlations were substantial (0.4-0.5) but did not reach statistical significance. This suggests that the challenges have different mechanisms or pathways leading to bronchoconstriction, and assessment of the pattern of individual patients' bronchial hyperresponsiveness may require application of a number of different bronchial challenge tests. For routine use histamine challenge seems the most appropriate. PMID- 1514664 TI - Enhanced production of platelet activating factor by peripheral granulocytes from children with asthma. AB - Granulocytes from 23 asthmatic children aged 4-15 years and 32 age-matched healthy children were studied. Cells were purified by Dextran sedimentation and Percoll gradient centrifugation from heparinized blood. After in vitro stimulation by ionophore A23187 the amount of newly synthesized PAF and LTC4 was assessed by radio receptor assay or radioimmunoassay respectively. Eight patients had symptoms of asthma within the last 3 weeks before examination. Granulocytes from the symptomatic patients showed a significantly higher PAF generation (median 125 ng/10(6) cells, range 7-189 ng/10(6) cells) when compared to asymptomatic patients (p less than 0.001, median 14 ng/10(6) cells, range 6-33 ng/10(6) cells) or controls (p less than 0.001, median 11 ng/10(6) cells, range 3 26 ng/10(6) cells). In contrast, LTC4 generation was increased in both patient groups. The results suggest a regulatory role of PAF in the exacerbation of asthma. PMID- 1514665 TI - Natural history of bronchial asthma in childhood. A prospective study from birth up to 12-14 years of age. AB - In a cohort of 1654 consecutively born children followed from birth, the cumulated incidence of asthma up to 11 years was 5.3% and the prevalence 3% between 10 and 11 years of age. The asthma debut was prior to 1.5 years in 1/3 and before 3 years in 1/2 of the children. Among 59 children examined at 11.5 14.5 years of age, 16 (27%) had no prevalent asthma. On the other hand, inadequate medication was found in 13, undiagnosed chest deformity in four, and wheezing in seven children. All 54 tested children including those with no prevalent asthma had a PC20 histamine less than 8 mg/ml. Tread mill test gave a significant reaction in 15 children. Animal danders and pollens were the most common allergens giving reactions at skin prick test. Compared to one earlier Swedish study an increase in mite sensitivity was found. Cord-blood IgE concentration and a positive immediate family history of atopic disease had no predictive value for the severity of asthma at this follow-up. A new total asthma score including number of days with functional impact of asthma during the last year and present medication was used for group comparisons. Children with a high score at 11.5-14.5 years had more exercise-induced asthma, more concomitant allergic diseases, earlier asthma start, more chest deformity, hyperreactivity both on tread mill and histamine challenge tests, elevated IgE, positive Phadiatop and more reactions at skin prick test, especially to animals and mites. Bronchial asthma was found more often in children born during August through October, possibly due to unsuitable indoor climate and more virus infections during their first 6 months of life. The severity of the asthma was, however, not influenced by the month of birth. No significant differences were found between boys and girls regarding the age at debut, asthma severity at follow-up, or bronchial histamine threshold levels. PMID- 1514666 TI - Effect of inhaled formoterol versus terbutaline on respiratory function in moderate bronchial asthma. AB - In a double-blind cross-over study comparing the duration of action of 12 micrograms and 24 micrograms formoterol, 500 micrograms terbutaline and placebo, lung function tests were performed in 12 never-smokers with non-allergic bronchial asthma. All the patients were hyperreactive to methacholine, had normal serum IgE level, and negative skin or RAST results. The lung function tests were carried out over an 11-h period and included measurements of lung volumes, airway resistance, dynamic spirometry, nitrogen single breath wash-out test and single breath diffusion capacity for CO. The airway resistance and maximal forced expiratory flow tests indicated a pronounced bronchodilator effect without adverse effects of 12 micrograms and 24 micrograms formoterol on both large and peripheral airways. Improved intrapulmonary gas distribution measured by the nitrogen wash-out test and more even distribution of the lung volumes indicating more homogeneous ventilation was seen for approx. 3 h after terbutaline and approx. 11 h after 24 micrograms formoterol. Measurement of the CO diffusion capacity indicates more effective gas diffusion and a better ventilation perfusion ratio for at least 11 h, especially after inhalation of 24 micrograms formoterol. PMID- 1514667 TI - Genetic control of eosinophilia in guinea pig strains inbred for high or low bronchial allergic reactivity. 2. A genetic study of spontaneous and immunization induced eosinophilia. AB - In 4 inbred strains of guinea pig the tendency to develop peripheral high eosinophilia was shown to be genetically controlled. The development of eosinophilia with age and following immunization was examined in high- and low eosinophilic parental strains, in F1-hybrids and in backcross offspring. The results show that probably only one or a very few segregating genes control eosinophilia, and they also indicate that different genes are involved in the determination of spontaneous (age-related) and immunization-induced eosinophilia. PMID- 1514668 TI - Histamine-induced bronchoconstriction in conscious guinea pigs measured by strain gauge transduction. A new method. AB - A new objective method for measuring histaminedihydrochloride-induced bronchoconstriction in conscious guinea pigs has been developed. The aim of the present work was to investigate whether identical results could be obtained when the clinical observation of conscious guinea pigs with symptoms of respiratory distress (bronchoconstriction) was compared to an objective measuring technique of this parameter. An evaluation of the repeatability of the method was made and the respiration frequence (fR) and histaminedihydrochloride challenge concentration were compared to see whether there was a correlation between the two. Consequently, an apparatus was built that allowed simultaneous recording of breathing pattern and clinical observation of the animal being challenged. The breathing pattern was recorded by a strain-gauge transducer, connected to a measuring bridge, and the curves obtained on a jet ink x-y writer were used for calculating changes in duration of expiratory phase (Te) and fR. During the attacks of histaminedihydrochloride-induced bronchoconstriction a significantly prolonged Te could be calculated from the respiration curves. A high degree of agreement was found between this objective measure and clinically observed respiratory distress. The repeatability of the method was comparable to that of corresponding methods used for histaminedihydrochloride challenge in man. No obvious correlation was found between changes in fR and histaminedihydrochloride challenge concentration. PMID- 1514669 TI - High-dose inhaled steroids in the management of asthma. A comparison of the effects of budesonide and beclomethasone dipropionate on pulmonary function, symptoms, bronchial responsiveness and the adrenal function. AB - The efficacy of budesonide (800 micrograms b.d.) and beclomethasone dipropionate (750 micrograms b.d.) in controlling the symptoms of asthma, pulmonary function, bronchial responsiveness to histamine, and adrenal function, was assessed in a double-blind, double-dummy cross-over study of 36 adult chronic asthmatic patients. The patients, the majority of whom were assessed to be affected to a severe degree, were insufficiently controlled in their current regimen of inhaled steroids and/or inhaled and oral bronchodilators. A 2 weeks baseline period preceded 6 weeks of treatment with each of the study drugs. Both treatment groups showed improvements from baseline in clinical assessment of lung function carried out after the first 6 weeks of treatment. No significant differences were seen throughout the entire 12 weeks study, when comparing the effects of the treatments on FEV1, FVC, PEF or the histamine PC20. Asthma severity, symptom score and inhaled bronchodilator use showed the same results after both treatments. It is concluded that inhalations of budesonide and beclomethasone dipropionate in high doses are equally potent in the treatment of severe asthma. There is no significant influence on the adrenal function and no significant side effects during a period equal to that of the present study. PMID- 1514671 TI - Bronchial asthma induced by chick pea and lentil. AB - Allergic reactions to legumes through inhalation have rarely been described. We report the case of a 20-year-old man who experienced asthmatic attacks when exposed to the steam from cooking either chick pea or lentil. Type I hypersensitivity to the antigens in these legumes was demonstrated by means of immediate skin reactivity, histamine release tests, RAST and RAST inhibition. Specific bronchial challenges with the heated (75 degrees for 30 min) extracts of chick pea and lentil elicited isolated immediate responses. PMID- 1514670 TI - Involvement of arachidonate cyclooxygenase products in bronchial hyperresponsiveness induced by subthreshold concentration of aerosolized thromboxane A2 analogue (STA2) in guinea pigs. AB - Effects of a thromboxane synthetase inhibitor (OKY-046) and a cyclooxygenase inhibitor (indomethacin) on bronchial hyperresponsiveness induced by subthreshold concentration of aerosolized thromboxane A2 analogue (STA2) were investigated in anesthetized, artificially ventilated guinea pigs in order to examine the role of the cyclooxygenase pathway in bronchial hyperresponsiveness. Pretreatment with aerosolized OKY-046 significantly inhibited the bronchial hyperresponsiveness to histamine, but pretreatment with intravenous indomethacin showed a tendency to potentiate bronchial hyperresponsiveness. These results suggest that subthreshold concentration of thromboxane A2 contributes to bronchial hyperresponsiveness through activating the cyclooxygenase pathway including thromboxane A2 synthesis, and that the released cyclooxygenase products have an inhibitory effect on the bronchial hyperresponsiveness in guinea pigs. PMID- 1514672 TI - Development of increased airway responsiveness in two nurses performing methacholine and histamine challenge tests. AB - Two nurses who frequently examined patients with methacholine or histamine challenge tests developed increased airway responsiveness and symptoms of asthma. It is important to use a good system for evacuating the test aerosol during challenge tests. PMID- 1514673 TI - Occupational asthma in the confectionary industry caused by sensitivity to egg. AB - We report on a patient with asthma induced by occupational exposure to egg used to spray cakes before baking. A type I hypersensitivity to egg white was demonstrated by means of skin test, immunoassay for specific IgE, and immediate bronchial provocation test response to an egg white extract. PMID- 1514674 TI - Ascorbic acid and dehydroascorbic acid analyses in biological samples. PMID- 1514676 TI - Coomassie blue protein dye-binding assays measure formation of an insoluble protein-dye complex. AB - The solubility of the protein-Coomassie brilliant blue (CBB) complex formed upon Bradford (Anal. Biochem. 72, 248-254, 1976) or Sedmak and Grossberg (Anal. Biochem. 79, 544-552, 1977) protein assay has been investigated by centrifugation or filtration of the assay mix within 10 min of adding dye reagent. The results show complete loss of color yield in the respective supernates and filtrates. This indicates that the protein-CBB complexes are insoluble at the time of absorbance measurement. Protein solubility in the dye reagent may dictate the relative response of the assay to an individual protein and the requirement for macromolecular structure. PMID- 1514675 TI - Optimization and validation of analytical conditions for bovine serum albumin using capillary electrophoresis. AB - A quick and reproducible capillary electrophoresis method was optimized and validated for the assay of bovine serum albumin (BSA). The effects of various parameters such as pH of buffer, concentration of buffer, capillary dimensions, use of coated capillaries, and additives such as surfactants and protein solubilizers were evaluated. The capillary coatings or additives did not give any advantage in reducing the surface adsorption of BSA on the capillary walls. The optimized conditions include use of borate buffer, pH 8.5 having a concentration of 150 mM in a 27 cm capillary with an aperture window of 100 x 200 microns for detection. The optimized method for the detection of BSA was validated. The interday and intraday coefficient of variation was not greater than 7.59% at BSA concentrations of 25-1000 micrograms/ml. The method developed was reproducible and accurate. PMID- 1514677 TI - Fluorescent rotors and their applications to the study of G-F transformation of actin. AB - New fluorescent rotor molecules having hydrophilic functional groups, which are derivatives of p-(N,N-dialkylamino)benzylidenemalononitrile, were synthesized. Their properties as fluorescent rotors were confirmed by an observation of solvent viscosity-dependent fluorescence. Incorporation of hydrophilic groups into the molecules increased the solubility of fluorescent rotors in aqueous media; the application of the compounds to biochemical systems became feasible as a consequence. To demonstrate this applicability, we attempted to monitor the G-F transformation of rabbit skeletal muscle actin with these newly synthesized compounds. All the compounds carrying a malononitrile moiety showed greater fluorescence in F-actin. Among them, 1-(2-hydroxyethyl)-6-[(2,2-dicyano)vinyl] 2,3,4-trihydroquinoli ne gave the best result by the criteria of the difference in fluorescence quantum yield for G- and F-actin, solubility, and stability of the compound. The method has the major advantage of not requiring covalent modification of actin. PMID- 1514678 TI - A method for the determination of changes of glycolytic metabolites in yeast on a subsecond time scale using extraction at neutral pH. AB - Glucose metabolism in yeast can be stopped within 0.1 s by spraying the cells in 60% methanol at -40 degrees C. With this procedure the integrity of the cells is not damaged. Using stopped-flow equipment for the incubation with glucose, major changes within a second are shown to occur in intracellular glucose-6-phosphate whereas the fructose-1,6-bisphosphate concentration remains constant. After quenching, the cells can be separated from the medium, washed with cold methanol when required, and extracted using chloroform at -40 degrees C at neutral pH, ensuring minimal degradation of labile metabolites. With partly automated enzymatic methods, a large variety of metabolites, including all glycolytic intermediates, can be determined in the neutral extracts. During the first second after addition of glucose, a significant increase in free intracellular glucose is found. PMID- 1514679 TI - High-performance liquid chromatography determination of polydeoxyribonucleotides in plasma: its application to the determination of defibrotide's pharmacokinetics in the rabbit. AB - We describe an HPLC method for the determination of whole polydeoxyribonucleotides in animal plasma. This method was compared to a colorimetric method, which evaluates the sugar moiety of polydeoxyribonucleotides, and to an agarose gel electrophoresis method, which evaluates the whole polydeoxyribonucleotides as does the HPLC method, and was found to give results very close to those obtained with these two other methods. A pharmacokinetic study of the antithrombotic, profibrinolytic, polydeoxyribonucleotidic drug defibrotide was carried out by evaluating the plasma drug levels by these three methods. The pharmacokinetic parameters calculated from the data are very similar. PMID- 1514680 TI - Electroporation-mediated gene transfer into hepatocytes: preservation of a growth hormone response. AB - An electroporation procedure is described which allows the introduction of foreign genes into freshly isolated rat hepatocytes while preserving their growth hormone responsiveness. A single-pulse procedure performed at low voltage (150 200 V) but with high capacitance (960 microF), conditions which caused minimal cell damage and increased hepatocyte survival in culture (greater than 80%), was found to be optimal for both the basal and the hormone-stimulated expression of transfected genes. Transfection of the cells suspended in a phosphate buffer at high concentrations (20-25 x 10(6)/ml) with large amounts of plasmid (30 micrograms/assay) gave the best results. Raising the temperature up to 25 or 37 degrees C (instead of 4 degrees C) decreased about twofold basal CAT expression but appeared to increase the magnitude (i.e., fold induction) of hormonal effects. Expression of the reporter gene driven by either a viral or a liver gene promoter reached a maximum after 24 h, a situation especially favorable when studying liver-specific gene expression known to decay rapidly in cultured hepatocytes. This procedure was successfully applied to the study of a growth hormone-dependent serine protease inhibitor gene promoter. PMID- 1514681 TI - The characteristic negative Cotton effect of ganglioside lactones observed by circular dichroism spectrometry. AB - Circular dichroism spectrometry was applied to gangliosides and their lactones and revealed that the lactones have a characteristic strong negative Cotton effect around 235 nm. Four monolactones and two dilactones, which were formed from GM4, GD3, and GD1b, gave molar ellipticities at the wavelength in magnitude of 10(4), while their parent gangliosides, along with other gangliosides such as GM3, GM1, GD1a, GT1b, and GQ1b, showed no distinct feature. Two ganglioside esters, GM4-methyl ester and O-Ac-GT1b did not show the Cotton effect. The molar ellipticities had an additivity with respect to the number of lactone rings. The Cotton effect was attributed to the carbonyl group on the lactone ring. PMID- 1514682 TI - Monosaccharide determination of glycoconjugates by reverse-phase high-performance liquid chromatography of their phenylthiocarbamyl derivatives. AB - A method for the determination of neutral sugars and hexosamines present in glycoconjugates by reverse-phase high-performance liquid chromatography (HPLC) of their phenylthiocarbamyl (PTC) derivatives has been developed. After acid hydrolysis, neutral sugars are converted to glycamines by reaction with ammonium acetate in the presence of sodium cyanoborohydride and are subsequently derivatized with phenylisothiocyanate, while the hexosamines present in the same hydrolysate, after separation on Dowex 50, are treated directly with this reagent. HPLC of the PTC-glycamines of the neutral sugars is performed on Microsorb C18 in an isocratic manner while chromatography of the PTC-hexosamines employs a Pico-Tag column with gradient elution to achieve separation from the PTC-amino acids. The procedure has proven to be highly sensitive, requiring as little as picomole amounts for the chromatographic step; monosaccharide compositions determined on glycoproteins and glycopeptides by this method were found to compare favorably to those previously obtained by other techniques. PMID- 1514683 TI - Profiling assay for lipoxygenase products of linoleic and arachidonic acid by gas chromatography-mass spectrometry. AB - A method for determination of the lipoxygenase products of linoleic acid (9- and 13-hydroxyoctadecadienoic acid; 9-HODE, 13-HODE) and of arachidonic acid (5-, 8-, 9-, 11-, 12-, and 15-hydroxyeicosatetraenoic acid; 5-, 8-, 9-, 11-, 12-, and 15 HETE) is described. The method combines solid-phase extraction, derivatization to the corresponding fully hydrogenated methylester/trimethylsilylether derivatives and capillary gas chromatography coupled with electron impact mass spectrometry. Each regioisomeric HODE and HETE shows a unique pair of mass spectrometric fragment ions originating from fission of the fatty acid carbon chain at the hydroxylated position. The carboxyl-terminal fragment is used for quantification relative to a carboxyl-18O2-labeled analogue added as internal standard and the methyl-terminal fragment is monitored for confirmation. The assay can be extended for quantification of the complete hydroxylation profile of linoleic and arachidonic acid. Applications of this assay are demonstrated for the quantification of HODEs and HETEs in normal, hyperplastic, and neoplastic mouse epidermis. In mouse epidermis papilloma, the tissue levels of 8- and 12-HETE were found to be increased by one to two orders of magnitude compared to levels in normal epidermis. PMID- 1514684 TI - Triple-label beta liquid scintillation counting. AB - The detection of radioactive compounds by liquid scintillation has revolutionized modern biology, yet few investigators make full use of the power of this technique. Even though multiple isotope counting is considerably more difficult than single isotope counting, many experimental designs would benefit from using more than one isotope. The development of accurate isotope counting techniques enabling the simultaneous use of three beta-emitting tracers has facilitated studies in our laboratory using the multiple tracer indicator dilution technique for assessing rates of transmembrane transport and cellular metabolism. The details of sample preparation, and of stabilizing the liquid scintillation spectra of the tracers, are critical to obtaining good accuracy. Reproducibility is enhanced by obtaining detailed efficiency/quench curves for each particular set of tracers and solvent media. The numerical methods for multiple-isotope quantitation depend on avoiding error propagation (inherent to successive subtraction techniques) by using matrix inversion. Experimental data obtained from triple-label beta counting illustrate reproducibility and good accuracy even when the relative amounts of different tracers in samples of protein/electrolyte solutions, plasma, and blood are changed. PMID- 1514685 TI - Chromatographic separation of oligodeoxynucleotides with identical length: application to purification of oligomers containing a modified base. AB - A general procedure is described for separation and purification of oligodeoxynucleotides of identical length but different base composition, in particular, of oligomers containing modified bases such as 4-substituted thymines and 6-substituted guanines, using an anion-exchange column (either Mono Q or NucleoPac). The modified oligomers can be well separated from the analogous oligomers containing unmodified thymine or guanine under the basic conditions of the chromatography. The effects of oligomer length, base composition, and lipophilicity on the separation are discussed. A general rule which can be used for prediction of the order of elution of different oligomers and for estimation of tautomeric form of a modified base in the oligomer is presented. PMID- 1514686 TI - Analysis of human synovial fluid phospholipase A2 on short chain phosphatidylcholine-mixed micelles: development of a spectrophotometric assay suitable for a microtiterplate reader. AB - The development of a reliable assay for human synovial fluid phospholipase A2 (HSF PLA2) is important for the kinetic characterization of the enzyme and for the identification of enzyme inhibitors. This enzyme behaves differently from other extracellular PLA2s in many standard phospholipase assays and is generally assayed using radiolabeled, autoclaved Escherichia coli as a substrate. We have now developed a nonradioactive, continuous, spectrophotometric assay for this enzyme that is adaptable for use with a microtiterplate reader and is suitable for screening enzyme inhibitors. The assay uses a thioester derivative of diheptanoyl phosphatidylcholine as a substrate, with which the enzyme displays a specific activity of about 25 mumol min-1 mg-1. The substrate concentration curve fits a Hill equation with an apparent Km of 500 microM and a Hill coefficient of two. The enzyme has a pH optimum of 7.5 in this assay and requires about 10 mM Ca2+ for maximal activity. The presence of 0.3 mM Triton X-100 was necessary to solubilize the substrate; however, higher concentrations of the detergent inhibited enzyme activity. Using this spectrophotometric assay, inhibition of HSF PLA2 by a thioether phosphonate phosphatidylethanolamine analog was observed with an IC50 of 18 microM. PMID- 1514687 TI - Development of screening methods for detection of carbohydrate-binding proteins by use of soluble glycosylated polyacrylamide-based copolymers. AB - Mammalian endogenous carbohydrate-binding proteins (lectins) play fundamental roles in a variety of mechanisms of interactions both at the molecular and cellular levels. We have investigated the binding of one of them (human brain lectin) to soluble acrylamide copolymerized with derivatives of either lactose (O beta-lactosyloxyallylallylaminoacrylamide copolymer) or D-mannose (D-alpha mannosyloxyallylallylaminoacrylamide copolymer) in direct enzyme affinoassays, in an attempt to develop simple procedures for detection and estimation of its carbohydrate-binding activity. Biotinylated plant lectins were utilized as reference standards. Affinoassays employed the polymer dotted on nitrocellulose and the polymer coated on microtiter plates as well as detection of bound biotinylated lectin by streptavidin/horseradish peroxidase reagent. Both assays provided reproducible binding, inhibitable by specific sugars. The microtiter plate assay is well suited to sensitive detection of the negative endogenous lectin by competition with biotinylated brain lectin. We conclude that the use of derivatized acrylamide in dotting and microtiter plate assays may prove practical for detection of endogenous lectins and that such polymers may serve as model substances in the study of biological partners of these carbohydrate-binding proteins. PMID- 1514688 TI - Continuous spectrophotometric assay for restriction endonucleases using synthetic oligodeoxynucleotides and based on the hyperchromic effect. AB - A continuous spectrophotometric assay for the EcoRV restriction endonuclease has been developed. The synthetic self-complementary oligonucleotide d(GACGATATCGTC) (which is double stranded under the assay conditions) is used as the substrate. The EcoRV endonuclease recognizes d(GATATC) sequences cutting between the central T and dA bases. Thus d(GACGATATCGTC) is converted to d(GACGAT) and d(pATCGTC) during catalysis. Both of the hexameric products are single stranded under the assay conditions. The conversion of the dodecameric substrate to the two hexameric products and the concomitant change from double- to single-stranded DNA is associated with an increase in absorbance at 254 nm due to the hyperchromic effect. This change can be used to monitor column effluents for endonuclease activity and also for Km and kcat determination under steady-state kinetic conditions. PMID- 1514689 TI - Assay of alpha 1,3 N-acetyl-D-galactosaminyl transferase by affinity chromatography. AB - A high-performance liquid affinity chromatography column that contains immobilized anti-A monoclonal antibody specifically retards blood group A-active oligosaccharides and can be used to detect the product(s) of the reaction catalyzed by alpha-1,3-N-acetyl-D-galactosaminyltransferase: [formula: see text] After a brief incubation (15 min) of an assay mixture containing 1-100 microliters human serum, the sugar nucleotide donor UDP-GalNAc, and radiolabeled oligosaccharide acceptors 2'-fucosyllactose and/or lacto-N-fucpentaose I blood group A-active products are isolated and quantitated in a single affinity chromatographic step that takes less than 30 min. Kinetic studies to determine the pH optima for serum alpha-3-GalNAc transferase from individuals of blood groups A1 and A2 and the Km value for UDP-GalNAc for the A1 transferase agree with previous determinations. As monoclonal antibodies against many different complex carbohydrate antigens are now available, the method described could be adapted to give rapid, inexpensive assays for a variety of glycosyltransferases. PMID- 1514690 TI - Allele-specific and asymmetric polymerase chain reaction amplification in combination: a one step polymerase chain reaction protocol for rapid diagnosis of familial defective apolipoprotein B-100. AB - We have combined the asymmetric polymerase chain reaction (PCR) with allele specific PCR to detect a single point mutation. A set of two priming oligonucleotides and a third allele-specific primer were used to identify heterozygotes for a G to A mutation at nucleotide 10,708 in the apolipoprotein B (apo B) gene. The system requires neither restriction enzyme digestion nor allele specific oligonucleotides as conventionally applied for allele-specific hybridization of slot blots. This method clearly allows for the detection of the mutant allele by inspection, after agarose gel electrophoresis of a single PCR reaction. DNA from 40 patients with familial defective apo B-100 due to the G to A mutation at nucleotide 10,708 in the apo B gene and their normal relatives was analyzed. Complete agreement with allele-specific hybridization of slot blots confirms supposition that the system is effective to screen a larger population. PMID- 1514691 TI - Immunodetection of biotinylated lymphocyte-surface proteins by enhanced chemiluminescence: a nonradioactive method for cell-surface protein analysis. AB - Biotinylation and radioiodination have been compared for labeling lymphocyte surface proteins and the labeled proteins symmetrically immunoprecipitated with antibodies recognizing major lymphocyte markers such as the murine Thy-1, CD25 (the alpha subunit of the interleukin-2 receptor), CD45, and human CD2 glycoproteins. The detection of biotinylated proteins by enhanced chemiluminescence after transfer to nitrocellulose was found to be fast and as efficient as the detection of iodinated proteins by autoradiography. The vectoriality of cell-surface biotinylation was ascertained by two-dimensional electrophoresis of the cellular extract in which the major cytoplasmic proteins were not found biotinylated. This nonradioactive labeling procedure offers a convenient and efficient alternative to radiolabeling of cell surfaces for the biochemical analysis of extracellular domains of membrane proteins. PMID- 1514692 TI - A method for the evaluation of the efficiency of signal sequences for secretion and correct N-terminal processing of human parathyroid hormone produced in Escherichia coli. AB - Expression plasmids have been constructed for evaluation of different signal sequences for secretion and correct amino terminal processing of foreign proteins expressed in Escherichia coli. cDNA representing the N-terminal region (1-37) of human parathyroid hormone was inserted between DNA coding for two different forms of the signal sequence and two IgG binding domains (ZZ) derived from Staphylococcal protein A. The expression products were secreted to the periplasm and even to the growth medium and were easily purified by affinity chromatography using the ZZ part as a specific handle. Further analyses showed that the expression products were correctly processed to the mature protein hPTH(1-37)ZZ in a construct where the wild type signal sequence of Staphylococcus protein A was used. When a mutated signal sequence which lacks the normal cleavage site was employed, the fusion protein was not cleaved. Since signal sequences seem to be processed in the correct way in this system, we conclude that the general design of this type of expression vector is well suited for studying the N-terminal processing and secretion of heterologous proteins in E. coli. PMID- 1514693 TI - Preparation of fatty-acylated derivatives of acyl carrier protein using Vibrio harveyi acyl-ACP synthetase. AB - A simple two-step purification of Vibrio harveyi fatty acyl-acyl carrier protein (acyl-ACP) synthetase, which is useful for the quantitative preparation and analysis of fatty-acylated derivatives of ACP, is described. Acyl-ACP synthetase can be partially purified from extracts of this bioluminescent bacterium by Cibacron blue chromatography and Sephacryl S-300 gel filtration and is stable for months at -20 degrees C in the presence of glycerol. Incubation of ACP from Escherichia coli with ATP and radiolabeled fatty acids (6 to 16 carbons in length) in the presence of the enzyme resulted in quantitative conversion to biologically active acylated derivatives. The enzyme reaction can be monitored by a filter disk assay to quantitate levels of ACP or by sodium dodecyl sulfate polyacrylamide gel electrophoresis and fluorography to detect ACP in cell extracts. With its broad fatty acid chain length specificity and optimal activity in mild nondenaturing buffers, the soluble V. harveyi acyl-ACP synthetase provides an attractive alternative to current chemical and enzymatic methods of acyl-ACP preparation and analysis. PMID- 1514694 TI - Quantitative fluorometric analysis of plant and microbial chitosanases. AB - A quantitative fluorometric assay for chitosanase activity in bacterial and plant tissues was developed. The assay can be conducted with either finely milled preparations of chitosan in suspension or dissolved chitosan; activity is based on measurements of glucosamine (GlcN) or oligomers of GlcN. GlcN is detected fluorometrically after reaction with fluorescamine with detection in the nanomole range. Fluorescence measurements of chitosanase activity and radioassay of chitinase in commercial preparations of chitinase from Streptomyces griseus revealed that both activities were present. Specific activities for the S. griseus chitosanase using suspended and soluble chitosans were respectively 1.24 and 6.4 mumol GlcN.min-1.mg protein-1. Specific activity of the S. griseus chitinase was 0.98 mumol GlcN.min-1.mg protein-1. Sweet orange callus tissue was tested for chitosanase and chitinase activity. It was necessary to remove small amine-containing molecules from the callus preparations before chitosanase activity could be assayed. The specific activity for chitinase and chitosanase in desalted extracts of nonembryogenic Valencia sweet orange callus tissue was determined to be 18.6 and 89.4 nmol GlcN.min-1.mg protein-1, respectively. PMID- 1514695 TI - Adenine and guanine nucleotide content of Triton-extracted cytoskeletal fractions of nonmuscle cells. AB - Determination of the adenine and guanine nucleotides in Triton X-100-extracted cytoskeletal fractions was utilized to estimate the actin and tubulin content of the assembled cytoskeletons in nonmuscle cells. Results with stable cell lines (i.e., rat pheochromocytoma PC12 and neuroblastoma NB41A3) and with primary cultures (i.e., human foreskin fibroblasts and chick embryonic dorsal root ganglion neurons) exhibited levels of cytoskeletal fraction ADP and GDP consistent with their assembly-induced nucleoside-5'-triphosphatase activities only previously analyzed in vitro. Likewise, estimates of actin and tubulin content fall in the range of values obtained by other experimental approaches. In contrast, analysis of whole cell nucleotides showed high [ATP]/[ADP] and [GTP]/[GDP] ratios, suggesting there is little, if any, contamination of the cytoskeletal nucleotide pool by other cellular nucleotides. PMID- 1514696 TI - Comparison of spectrum-shifting intracellular pH probes 5'(and 6')-carboxy-10 dimethylamino-3-hydroxyspiro[7H-benzo[c]xanthene-7, 1'(3'H)-isobenzofuran]-3'-one and 2',7'-biscarboxyethyl-5(and 6)-carboxyfluorescein. AB - The dyes carboxy-SNARF-1 and BCECF are fluorescent probes of intracellular pH that exhibit changes in spectral shape upon proton binding which allow one to use measurements of fluorescence at two or more wavelengths in order to measure pH without artifacts associated with variability in dye loading, etc. In evaluating these dyes for this study, whole spectra, rather than measurements at two wavelengths, were analyzed. For BCECF, the effects of the intracellular milieu were minimal: both the pH-sensitive excitation spectrum and the pKa agreed closely with values found in extracellular solution. In contrast, both the spectra and the pKa for the emission spectrum-shifting carboxy-SNARF-1 showed significant differences between intracellular and extracellular dye. As a result, extremely misleading values for intracellular pH will be obtained if one attempts to use extracellular dye to calibrate intracellular carboxy-SNARF-1 measurements. Multiple origins were found for the discrepancy: (i) the intracellular dye was found to be significantly quenched, with the deprotonated form being more strongly quenched than the protonated form; and (ii) the pKa for the equilibrium with intracellular hydrogen ions was shifted by +0.2 pH units. These effects were readily reversed by disruption of the cell, but were not due to sequestering of dye in an acidic cell compartment. PMID- 1514697 TI - Quantitation of lysophosphatidylcholine molecular species in rat cardiac tissue. AB - We have developed a rapid and sensitive procedure for isolation and measurement of 1-acyllysophosphatidylcholine (LPC) species in rat myocardial tissue. Tissues were spiked with heptadecanoyl-LPC internal standard and extracted with chloroform/methanol. The chloroform phase was dried, resuspended in chloroform/propan-2-ol (2/1, v/v), and applied to an aminopropyl-bonded phase (Bond Elut) column. Following stepwise elution with several solvent mixtures, the LPC fraction (ethyl acetate/methanol, 4/6, v/v) was separated by HPLC with direct quantitation of palmitoyl-LPC (P-LPC), oleoyl-LPC (O-LPC), and stearoyl-LPC (S LPC), using an evaporative light scattering mass detector. Calibration curves were generated for each individual LPC species. Recoveries of added [14C]LPC and of heptadecanoyl-LPC internal standard after extraction and chromatography were 85.8 +/- 1.9% (mean +/- SE, N = 10) and 83.4 +/- 1.8% (N = 15), respectively. This assay showed satisfactory sensitivity, reproducibility, and accuracy for measurement of LPC species in rat myocardial tissue. The major molecular species of LPC in rat myocardium were found to be P-LPC and S-LPC, which were two- to sixfold as abundant as O-LPC. In isolated, crystalloid-perfused rat hearts the time of perfusion was found to significantly influence the content of P-LPC (0 min, 252 +/- 10; 15 min, 178 +/- 10, P less than 0.001, compared with 0 min; 40 min, 131 +/- 4, P less than 0.001; and 70 min, 129 +/- 4, P less than 0.001; nmol/g dry weight), but not the content of O-LPC and S-LPC. The method will be useful for studying the participation of LPC species in physiology, pathophysiology, and therapeutics. PMID- 1514698 TI - The human platelet as a reproducible and sensitive cell for the detection and assay of platelet-activating factor. AB - A new procedure for the preparation of human platelets consistently sensitive to platelet-activating factor (PAF) in the low nanomolar range has been developed. Key to the success of this approach was the addition of adenosine during the isolation phase, providing an excellent recovery of stable cells, and the inclusion of ADP in the aggregation assay, providing increased sensitivity to PAF. Examination of the binding profile of tritium-labeled PAF to these platelets in the presence or absence of ADP revealed significant difference in the Kd values but not in the number of specific binding sites. Other reagents having an influence on the reactivity and stability of the human platelets, as regards its interaction with PAF, are described. PMID- 1514699 TI - Preparative labeling of proteins with [35S]methionine. AB - The most common technique for preparative labeling of proteins with radioisotopes for experimental purposes utilizes 125I. This isotope has certain limitations, including the emission of gamma- and X-irradiation, the release of gaseous 125I2 from solutions of Na 125I, and the potential for concentration of 125I in thyroid glands. We have discovered a means for labeling proteins rapidly and simply with [35S]methionine. The technique is applicable to a wide variety of proteins. Antibodies labeled by our technique remain functional. PMID- 1514700 TI - Application of a fluorogenic substrate in the assay of proteolytic activity and in the discovery of a potent inhibitor of Candida albicans aspartic proteinase. AB - A fluorescent method for monitoring the activity of the secreted Candida carboxyl (aspartic) proteinase (EC 3.4.23.6) was developed using a fluorogenic substrate based on resonance energy transfer. The fluorescent assay was used to monitor proteinase production, purification, and inhibition. The Km for the fluorogenic substrate, 4-(4-dimethylaminophenylazo)benzoyl-gamma-aminobutyryl-Ile-His-Pro - Phe-His-Leu-Val-Ile-His-Thr- [5-(2-aminoethyl)amino]naphthalene-1-sulfonic acid, was found to be 4.3 microM at the optimum pH of 4.5. Reaction products were separated by reverse-phase high-performance liquid chromatography and identified by amino acid analysis or by 252Cf plasma desorption mass spectrometry. Cleavage of the fluorogenic substrate was between the histidine-threonine residues, releasing the fluorescent product, threonine-[5-(2-aminoethyl)amino]naphthalene-1 sulfonic acid. Proteolytic activity was expressed as nanomoles of fluorescent product released at 22 degrees C/60 min, pH 4.5, and the release of 0.9 nmol product was equivalent to one hemoglobin proteolytic unit (O.D.A700 increase of 0.100) produced at 37 degrees C/60 min, pH 3.5. The aspartic proteinase inhibitor pepstatin had an IC50 of 27 nM when tested in a dose-response study with the purified enzyme. The apparent Ki for pepstatis was 2.9 nM. Several synthetic inhibitors of the enzymes were identified with IC50's in the nanomolar range. The most potent compound, A70450, was characterized as a fast, tight-binding inhibitor having an IC50 of 1.3 nM and apparent Ki of 0.17 nM. PMID- 1514701 TI - Interdigital chondrogenesis and extra digit formation in the duck leg bud subjected to local ectoderm removal. AB - In the chick embryo the interdigital tissue in the stages previous to cell death exhibits in vitro a high chondrogenic potential, and forms extra digits when subjected in vivo to local ectodermal removal. In the present work we have analyzed the chondrogenic potential both in vivo and in vitro of the interdigital mesenchyme of the duck leg bud. As distinct from the chick, the interdigital mesenchyme of the duck leg bud exhibits a low degree of degeneration, resulting in the formation of webbed digits. Our results show that duck interdigital mesenchyme exhibits also a high chondrogenic potential in vitro until the stages in which cell death starts. Once cell death is finished chondrogenesis becomes negative and the interdigital mesenchyme forms a fibroblastic tissue. In vivo the interdigital mesenchyme of the duck leg bud subjected to ectoderm removal forms ectopic foci of chondrogenesis with a range of incidence similar to that in the chick. Unlike those of the chick the ectopic cartilages of the duck are rounded and smaller, and appear to be located at the distal margin of the interdigital mesenchyme. Formation of extra digits in the duck occurs with a lower incidence than in the chick. It is concluded that ectopic chondrogenesis and formation of extra digits is related to the intensity of interdigital cell death. The non degenerating interdigital mesenchymal cells destined to form the interdigital webs of the duck appear to contribute very little to the formation of interdigital cartilages. PMID- 1514702 TI - Scanning electron microscopy of esophageal microvasculature in human infants and rabbits. AB - The microvasculature of the esophagus was studied by scanning electron microscopy of vascular corrosion casts in human infants and rabbits. In both species, segmental circumferential arteries arise from main longitudinal arteries, the latter giving off numerous perforating arteries. The tunica muscularis is supplied by branches of circumferential and perforating arteries, the submucosa and its glands by branches of perforatings. Terminal arborizations of perforating arteries feed a subepithelial capillary network. These capillaries are drained by a venous plexus in the lamina propria which is connected to a submucosal venous plexus. Perforating veins, running parallel to the corresponding arteries, connect the submucosal plexus with circumferential veins, and finally empty into main longitudinal veins. Valves were not present in any of the veins. Submucosal veins were less numerous in man than in rabbit. The number and caliber of equivalent vessels in human submucosal plexus decreased from the pharyngoesophageal to the gastroesophageal junction, suggesting the latter to be at particular risk in portal hypertension. The subepithelial capillary network reveals a longitudinal arrangement in rabbits, while the same network shows no preferential organization in human infants. The microvascular architecture of the esophagus in humans and rabbits is comparable, especially in the lay-out of the venous plexuses and the absence of venous valves. Therefore the rabbit could serve as an experimental model for studies on portal hypertension. The present results strongly suggest particular significance of the venous plexus in the lamina propria for the genesis of esophageal varices. PMID- 1514703 TI - Embryonic development of the house shrew (Suncus murinus). I. Embryos at stages 9 and 10 with 1 to 12 pairs of somites. AB - The embryonic development during the period from 1 to 12 pairs of somites was observed in an insectivore species, the house shrew (Suncus murinus), which has been bred within a closed colony. Embryos were staged by the number of somite pairs. Each stage was punctuated at every addition of three pairs of somites and numbered after the Carnegie system. The first somite became apparent between 8 and 9.0 days after fertilization, and the 12th somite appeared between 9.5 and 10.0 days. The rate of somite formation was one pair in every 3-4 h on average. The embryonic events during this period were as follows: 1. From the beginning of stage 9, the embryonic body consistently displayed a kyphosis, and as development progressed, the caudal portion of the embryo spiralled clockwise. 2. The first and second pharyngeal arches formed; their development was precocious among mammalian embryos in relation to somitic count. 3. The segmental pattern of the neural fold was similar to that of laboratory rodents and primates. The first fusion of the cranial neural folds took place in the occipital somite region, the second fusion in the diencephalic region, and the third at the end of the neural plate, thus leaving two neuropores in the cephalic region. 4. The timing of appearance of the optic sulcus was similar to that of human embryos but was delayed in comparison with that of laboratory rodents. 5. The heart always showed a more advanced state than that of other mammalian embryos. From the beginning of stage 9, an unpaired endocardial tube was seen in the bulbo-ventricular region, and deflection from a symmetrical appearance soon took place. 6. The differentiation of foregut was also precocious, and the thyroid and respiratory primordia appeared earlier than in other mammals. The present study emphasizes that there are considerable variations in timing and manner of morphogenesis among early mammalian embryos. PMID- 1514704 TI - The regulative potential of the limb region in 11.5-day rat embryos following the amputation of the fore-limb bud. AB - The regulative potential of the fore-limb region following the removal of the limb bud was investigated in 11.5-day rat embryos. Fore-limb buds were amputated from a total of 54 embryos. Five embryos were immediately examined via scanning electron microscopy (SEM) to assess the quality of the operation and the reproducibility of the technique. In all cases, the forelimb bud and adjacent tissues extending down to the celomic cavity at the same level were completely removed. The remaining 49 operated embryos were cultured in vitro and examined at different time intervals. Gross inspection of embryos which had been cultured for 24 h, revealed that 24 out of 37 had developed a pair of limb bud-like protrusions at the operation site. Twelve formed only a single protrusion, while nothing was found in the remaining embryo. These protrusions were examined in greater detail under SEM and light microscopy. SEM observations showed that these protrusions were covered with an intact layer of ectoderm. In embryos with a pair of protrusions, these outgrowths developed opposite somites 7 to 13. The failure of either one of these two outgrowths to form, produced our second type of experimental embryo, those which had just a single protrusion. Histological examination revealed that an apical ectodermal ridge (AER) was discernible on the protrusions of 36% of the embryos. Finally, we have established how these protrusions were constructed from SEM observations of operated embryos cultured for 6 h and 10 h. PMID- 1514705 TI - Regeneration in the Xenopus tadpole optic nerve is preceded by a massive macrophage/microglial response. AB - Changes in the optic nerve following a crush lesion and during axonal regeneration have been studied in Xenopus tadpoles, using ultrastructural and immunohistological methods. Degeneration of both unmyelinated and myelinated axons is very rapid and leads to the formation, within 5 days, of a nerve which consists largely of degeneration debris and cells. Immunohistological analysis with monoclonal antibody 5F4 shows that there is a rapid and extensive microglial/macrophage response to crush of the nerve. Regenerating axons have begun to enter the distal stump by 5 days and grow along the outer part of the nerve in close approximation to the astrocytic glia limitans. Between 5 and 10 days after nerve crush, regenerating axons reach and pass the chiasma. Macrophages are seen in the nerve at the site of the lesion within 1 h, and the response peaks between 3-5 days, just before axonal regeneration gets under way. PMID- 1514706 TI - Development and hormonal regulation of mast cells in the Harderian gland of Syrian hamsters. AB - The morphological features and relative number of mast cells per mm2 were studied in the Harderian glands of male and female Syrian hamsters (Mesocricetus auratus) under different experimental conditions. The structural and ultrastructural characteristics of Harderian mast cells corresponded to those of connective tissue mast cells. The Harderian glands from female hamsters contained more mast cells than those of male hamsters. A subcutaneous implant of testosterone (2 mg/24 mg beeswax) resulted in a rapid decrease in the number of recognizable mast cells 6 h after the implantation. Neither orchidectomy nor ovariectomy significantly altered the relative number of mast cells. However, the daily subcutaneous injection of 20 IU of human chorionic gonadotropin during 20 days resulted in a significant decrease of identifiable mast cells. The administration of another steroid such as progesterone or the induction of states of hypo- and hyperthyroidism did not alter the distribution of mast cells in the Harderian glands of female Syrian hamsters. PMID- 1514707 TI - Morphometrical variations of prolactin cells in response to prolonged and systemic administration of Met-enkephalin in female rats. AB - A stimulatory effect on prolactin secretion had been describe after acute and systemic administration of met-enkephalin, but the effects of this opioid after chronic administration has not been reported, and the response of mammotroph cells is not clear. As a complement to previous studies, a morphometric analysis (light and electron microscopy) was carried out on prolactin cells from female rats treated chronically with met-enkephalin. Clear features of cellular hyperactivity appeared after chronic and systemic administration of the opioid, and these persisted for two weeks. The changes consisted in increases of cellular, cytoplasmic and nuclear areas, volume and surface densities of the Golgi complex and rough endoplasmic reticulum, as well as the numbers of exocytotic figures. These morphological alterations were paralleled by an increase in serum prolactin levels as detected by RIA. It is concluded that the increase in the synthesis and secretory activity of prolactin cells following chronic and systemic administration of met-enkephalin is very similar to those observed after acute and intraventricular administration. PMID- 1514708 TI - Clinical application of magnetic resonance imaging of the heart and great vessels. AB - This report reviews the clinical applications of magnetic resonance imaging, (MRI) for the heart and great vessels based on the first 120 patients studied with 1.5 Tesla scanner. Cine scans were obtained in 85% of patients studied with the remainder having T1 spin-echo imaging. MRI provides high-resolution multiplanar images for defining abnormalities in cardiac structure and is especially useful for congenital heart disease. Cine MR evaluates cardiac dynamic functions such as left ventricular volumes and ejection fraction, left ventricular segmental wall motion, and valvular function. It is also useful for detection of aortic and pulmonary arterial disease and diseases of the pericardium. It is concluded that MR has broad applications for diagnosis of cardiac and great-vessel disorders. PMID- 1514709 TI - Iomeprol vs iopamidol in intraarterial peripheral digital subtraction angiography. AB - The aim of this research was to compare the efficacy and tolerability of iomeprol, 150 mg iodine/mL, a new nonionic contrast medium, and iopamidol, 150 mg iodine/mg in intraarterial (IA) peripheral digital subtraction angiography (DSA) in 100 patients; a group of 40 patients were also submitted to a complete coagulation screening to check the influence of contrast media on blood clotting. The study was a comparative, double-blind clinical trial. The compound was assigned to each patient according to a randomization list. Small size (4-5 French) catheters were used in all patients to minimize arterial trauma and bedding time and to assess the quality of x-ray pictures in this condition. Vital signs, EKG tracings and laboratory parameters were monitored before and after the angiographic procedure; the coagulation screening included: thrombin time, prothrombin time, partial thromboplastin time, euglobulin lysis time, plasma thromboplastin antecedent, and plasminogen activator inhibitor (PAI). Both contrast media did not produce any adverse reaction or clinically significant alteration of studied parameters; in the 40-patient group subjected to massive coagulative screening, no important alteration after contrast media administration was reported. The score for contrastographic efficacy was very good with both media with a prevalence of better results in the iomeprol group. PMID- 1514710 TI - Effects of intravenous streptokinase and CLS 2210 (calcium dobesilate) on the biochemical markers of early acute myocardial infarction: a historic comparison with both studies. AB - In a previous double-blind, randomized study, CLS 2210 (a new formulation of calcium dobesilate) or placebo was administered by intravenous infusion to 41 patients having their first acute myocardial infarction. In the present study 19 comparable patients were treated intravenously with streptokinase under identical conditions and the results compared with those from the previous study. In all patients administration was begun within three hours of onset of symptoms and continued over seventy-two hours. Blood samples were taken for the measurement of serum activity of creatine kinase and its isoenzyme MB, and the serum and urinary concentrations of myoglobin and glycosaminoglycans were also measured. The purpose of this study was to determine the effects of CLS 2210, placebo, and streptokinase on these biochemical markers of acute myocardial infarction, thereby assessing their actions in limiting myocardial necrosis. In the CLS 2210 treated patients, the levels of serum creatine kinase and serum and urinary myoglobin were significantly lower than in the placebo patients throughout the seventy-two hours (p = 0.01, 0.005, 0.004 respectively). The levels of creatine kinase MB and serum glycosaminoglycan in the CLS 2210 patients were initially higher than in the placebo patients but fell below placebo levels between the fortieth and fifty-fifth hours, respectively (p = 0.89, 0.02). Only the glycosaminoglycan urinary concentrations were higher in the CLS 2210 group than in the placebo group throughout (p = 0.0005). The values for the six variables investigated showed no statistically significant difference between placebo and streptokinase.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1514711 TI - Double-blind comparison of captopril with nifedipine in hypertension complicated by intermittent claudication. AB - In a double-blind, crossover trial 12 patients with hypertension and peripheral arterial disease were randomized to three months' treatment with captopril 25-50 mg twice daily or nifedipine SR 20-40 mg twice daily. While both treatments were equally effective at lowering blood pressure, postexercise calf blood flow availability was greater during treatment with captopril (P less than 0.04). This was not reflected in walking capacity assessed by treadmill exercise. The results suggest that both captopril and nifedipine are appropriate antihypertensive agents in patients with peripheral arterial disease. PMID- 1514712 TI - Effects of alternately aligned static micromagnetic fields on intravascular endothelial lining. AB - Effect of alternately aligned static micromagnetic fields on intravascular endothelial linings were investigated in 32 common carotid arteries of mongrel dogs. Endothelia of bilateral carotid arteries were mechanically denuded 5 cm in length, and as a general rule, 1 denuded artery was wrapped by a 1- or 5-cm-long film of alternately aligned static micromagnetic fields with 250 gauss/cm2 and the artery on other side (control) was not wrapped. The arteries were excised at weeks 1, 2, 3, 4, 5, 6, and 8 after endothelial denudation in order to examine the intraluminal surfaces of the distal, intermediate, and proximal portions of the specimen by light and scanning electron microscopy. Histopathologically, all the distal and proximal portions in each group were well lined with endothelium. There was, however, a significant difference between the experimental and control groups in the endothelial regeneration of the intermediate portion. Endothelial coverage of the serial specimens of the experimental group was found to occur earlier than that of the control group. Alternately aligned static micromagnetic fields accelerated the intravascular endothelial linings. PMID- 1514714 TI - Serum zinc concentration in acute myocardial infarction. PMID- 1514713 TI - Double-blind comparison of the clinical, hemodynamic, and electrocardiographic effects of sodium meglumine ioxaglate or iohexol during diagnostic cardiac catheterization. AB - The clinical effects and the maximal hemodynamic and electrocardiographic effects of two low-osmolality radiographic contrast media (ioxaglate and iohexol) were directly compared during diagnostic cardiac catheterization in a double-blind, randomized study in 80 patients. Because small changes were expected after injection of both of these agents, sensitive ECG and intracardiac-pressure monitoring methods were used, and maximal changes, as well as mean changes in variables, were analyzed. Symptoms were absent, mild, or moderate in 67-77% of patients after left ventriculography and in 97-100% of patients after coronary arteriography. After left ventriculography, maximum and minimum left ventricular systolic pressure and end-diastolic pressure, the first derivative of left ventricular pressure (dp/dt), heart rate, were significantly altered over the two minute observation period but were not different from the preinjection values at two minutes after both agents. Small but significant increases in mean aortic pressure, cardiac output, and pulmonary arterial wedge pressures were seen at two minutes after both agents. PMID- 1514715 TI - Use of cardiopulmonary bypass, high-dose epinephrine, and standard-dose epinephrine in resuscitation from post-countershock electromechanical dissociation. AB - STUDY OBJECTIVE: To determine the effects of cardiopulmonary bypass with standard dose epinephrine, high-dose epinephrine, and standard-dose epinephrine on perfusion pressures, myocardial blood flow, and resuscitation from post countershock electromechanical dissociation. DESIGN: Prospective, controlled laboratory investigation using a canine cardiac arrest model randomized to receive one of three resuscitation therapies. INTERVENTIONS: After the production of post-countershock electromechanical dissociation, 25 animals received ten minutes of basic CPR and were randomized to receive cardiopulmonary bypass with standard-dose epinephrine, high-dose epinephrine, or standard-dose epinephrine. MEASUREMENTS AND MAIN RESULTS: Myocardial blood flow was measured using a colored microsphere technique at baseline, during basic CPR, and after intervention. Immediate and two-hour resuscitation rates were determined for each group. Return of spontaneous circulation was achieved in eight of eight cardiopulmonary bypass with standard-dose epinephrine compared with four of eight high-dose epinephrine and three of eight standard-dose epinephrine animals (P less than .04). One animal was resuscitated with CPR alone and was excluded. Survival to two hours was achieved in five of eight cardiopulmonary bypass with standard-dose epinephrine, four of eight high-dose epinephrine, and three of eight standard dose epinephrine animals (NS). Coronary perfusion pressure increased significantly in the cardiopulmonary bypass with standard-dose epinephrine group when compared with the other groups (cardiopulmonary bypass with standard-dose epinephrine, 76 +/- 45 mm Hg; high-dose epinephrine, 24 +/- 12 mm Hg; standard dose epinephrine, 3 +/- 14 mm Hg; P less than .005). Myocardial blood flow was higher in cardiopulmonary bypass with standard-dose epinephrine and high-dose epinephrine animals compared with standard-dose epinephrine animals but did not reach statistical significance. Cardiac output increased during cardiopulmonary bypass with standard-dose epinephrine (P = .001) and standard-dose epinephrine (NS) compared with basic CPR but decreased after epinephrine administration in the high-dose epinephrine group (NS). CONCLUSION: Resuscitation from electromechanical dissociation was improved with cardiopulmonary bypass and epinephrine compared with high-dose epinephrine or standard-dose epinephrine alone. However, there was no difference in survival between groups. Cardiopulmonary bypass with standard-dose epinephrine resulted in higher cardiac output, coronary perfusion pressure, and a trend toward higher myocardial blood flow. A short period of cardiopulmonary bypass with epinephrine after prolonged post-countershock electromechanical dissociation cardiac arrest can re-establish sufficient circulation to effect successful early resuscitation. PMID- 1514717 TI - Minimal coronary stenoses and left ventricular blood flow during CPR. AB - STUDY OBJECTIVE: To assess the effect of a 33% coronary stenosis on myocardial blood flow during normal sinus rhythm and CPR. DESIGN: Prospective, before and after cardiac arrest and CPR; before and after creation of a 33% stenosis. SETTING: The University of Arizona Resuscitation Research Laboratory. SUBJECTS: Ten domestic closed-chest swine with patent coronary stenoses. INTERVENTIONS: A Teflon cylinder was placed in the mid-left anterior descending coronary artery to create a 33% stenosis. Myocardial blood flow was measured with colored microspheres both proximal and distal to the stenosis during normal sinus rhythm and during CPR. MEASUREMENTS AND MAIN RESULTS: During normal sinus rhythm, the stenosis did not alter the amount of myocardial blood flow distribution or quantity. Proximal to the stenosis the endocardial/epicardial flow ratio was 1.49 +/- 0.33, and distal to the stenosis it was 1.50 +/- 0.50. Likewise, during normal sinus rhythm, blood flow proximal and distal to the stenosis did not differ for either the epicardium (79 +/- 9 versus 66 +/- 13 mL/min/100 g) or the endocardium (111 +/- 27 versus 83 +/- 19 mL/min/100 g). However, the distribution of myocardial blood flow was markedly altered during CPR. The resultant endocardial/epicardial flow ratios were significantly less than during normal sinus rhythm, 0.49 +/- 0.11 (three minutes of CPR) and 0.74 +/- 0.07 (eight minutes of CPR) proximal to the stenosis and 0.39 +/- 0.15 (three minutes of CPR) and 0.49 +/- 0.14 (eight minutes of CPR) distal to the stenosis (P less than .05 versus normal sinus rhythm). In the presence of a 33% mid-left anterior descending coronary artery stenosis, endocardial blood flow at eight minutes of CPR was significantly lower distal to the stenosis compared with proximal to the stenosis (23 +/- 7 mL/min/100 g versus 74 +/- 18 mL/min/100 g; P less than .02). CONCLUSION: Minimal coronary lesions that do not diminish myocardial perfusion during normal physiologic conditions appear to significantly decrease subendocardial blood flow during cardiac arrest and CPR. PMID- 1514716 TI - Selective aortic arch perfusion during cardiac arrest: a new resuscitation technique. AB - STUDY OBJECTIVES: To demonstrate the technique of selective aortic arch perfusion during cardiac arrest and to observe the hemodynamic effects of volume infusion and aortic epinephrine administration. DESIGN: Sequential series, nonrandomized, noncontrolled. TYPE OF PARTICIPANTS: Fourteen mongrel dogs weighing 21 to 36 kg. INTERVENTIONS: Animals had midaortic arch pressure, right atrial pressure, and descending aortic arch balloon occlusion catheters placed. After ten minutes of ventricular fibrillation, balloon inflation and aortic arch infusions were initiated as follows: group 1 (six), 30 mL/kg/min of 0.9% NaCl for two minutes; group 2 (four), 30 mL/kg/min of oxygenated lactated Ringer's with 2 mg/L epinephrine for two minutes, followed by CPR; and group 3 (four), 20 mL/kg/min of oxygenated perfluorochemicals with 4 mg/L epinephrine for one minute, then CPR. MEASUREMENTS AND MAIN RESULTS: Midaortic arch pressure, right atrial pressure, and coronary perfusion pressure each rose significantly in all groups. Midaortic arch pressure and coronary perfusion pressure increases were greater in groups 2 and 3 than in group 1. In groups 1 and 2, right atrial pressure increases at end selective aortic arch perfusion were excessive as midaortic arch pressure and right atrial pressure increased linearly and similarly after 20 to 30 seconds. In groups 2 and 3, CPR-diastolic midaortic arch pressure and coronary perfusion pressure after selective aortic arch perfusion were good and similar to midaortic arch pressure and coronary perfusion pressure at end-selective aortic arch perfusion. CONCLUSION: Selective aortic arch perfusion is technically feasible, but excessive right atrial pressure increases limit maximal infusion rates and volumes. Selective aortic arch perfusion infusates with epinephrine produce greater midaortic arch pressure and coronary perfusion pressure during infusion than infusate without epinephrine. Controlled studies are needed to determine if selective aortic arch perfusion improves resuscitation outcome. PMID- 1514718 TI - The esophageal detector device: a rapid and accurate method for assessing tracheal versus esophageal intubation in a porcine model. AB - STUDY OBJECTIVES: To assess time and accuracy of the esophageal detector device (EDD), disposable end-tidal CO2 monitor (ETCO2), and standard clinical methods for detection of endotracheal tube placement. DESIGN: Prospective, randomized, single-blinded, controlled laboratory investigation. METHODS: Thirty airway managers (physicians, nurse anesthetists, and paramedics) used one pig (Sus scrofa) as the intubated, respiratory depressed/arrest model. INTERVENTIONS: Part 1: A standard 7.5-mm endotracheal tube was placed in either the esophagus or the trachea of the anesthetized swine. Anatomic location was verified by bronchoscopy. Airway managers blinded to the endotracheal tube location were assigned randomly to identify tube position by one of three methods (EDD, ETCO2, or clinical methods). Speed and accuracy of the assessment were recorded. Part 2: A second identical tube was placed, so that both the esophagus and the trachea were intubated; then, the esophageal tube was bag-ventilated for one minute. Each blinded airway manager, using only the EDD, determined placement site of both tubes. RESULTS: Part 1: Mean time to determine tube placement for group A (EDD) was 13.8 seconds; group B (ETCO2), 31.5 seconds; and group C (clinical methods), 39 seconds. Comparison by analysis of variance yielded a value of P less than .001. Both groups A and B were 100% accurate, whereas 30% of the subjects from group C mistakenly assessed an esophageal tube as in the trachea. Part 2: The EDD remained 100% sensitive and specific despite prior ventilation of the esophageal tube. CONCLUSION: In this porcine model, the EDD and ETCO2 were more accurate than clinical methods in determining endotracheal tube placement. The EDD demonstrated a significant time advantage over both ETCO2 and clinical methods. Prior ventilation of the esophageal tube does not interfere with the accuracy of the EDD. PMID- 1514719 TI - Effects of constriction bands on rattlesnake venom absorption: a pharmacokinetic study. AB - STUDY OBJECTIVE: To determine whether the use of a constriction band alters systemic absorption of rattlesnake venom in pigs and whether constriction band use alters local swelling. DESIGN: Using a crossover design, five pigs were studied with and without the use of a constriction band. 125I-Labeled Western Diamondback rattlesnake (Crotalus atrox) venom was injected subcutaneously into one foreleg. The protocol was repeated using the opposite foreleg six days later. The constriction band was applied at the time of injection and removed four hours later. Plasma radioactivity and leg circumference were measured serially. RESULTS: Maximum plasma venom concentration and area under the venom concentration-time curve were compared in trials with and without constriction band. Within the initial four hours, application of a constriction band decreased maximum plasma venom concentration by 25% and area under the venom concentration time curve by 33% (P less than .05). After the constriction band removal at four hours, maximum plasma venom concentration and the area under the venom concentration-time curve were not significantly different between groups. Application of a constriction band did not result in a statistically significant increase in maximum leg circumference as compared with trials without a constriction band. CONCLUSION: The use of a constriction band was effective in reducing venom absorption while it was in place (reduced area under the venom concentration-time curve and maximum plasma venom concentration in the cuffed group), and constriction band removal did not result in a significant increase in maximum plasma venom concentration. Leg swelling was not affected by constriction band use. Because constriction band use delayed venom absorption without causing increased swelling, it may prove to be a useful first aid measure in human beings. PMID- 1514720 TI - The clinical implications of continuous central venous oxygen saturation during human CPR. AB - STUDY OBJECTIVE: The purpose of this study was to observe, measure, and describe the changes in central venous oxygen saturation during CPR and immediately after return of spontaneous circulation. It also was to examine the clinical utility of continuous central venous oxygen saturation monitoring as a indicator of return of spontaneous circulation during CPR in human beings. DESIGN AND SETTING: Eight month, prospective, non-outcome, observational, nonrandomized case series in the ED of a large urban hospital. TYPES OF PATIENTS: Adult normothermic, nontraumatic, out-of-hospital cardiopulmonary arrests. INTERVENTIONS: All patients were managed according to advanced cardiac life support guidelines. A proximal aortic and double-lumen central venous catheter was placed. Central venous oxygen saturation was measured continuously spectrophotometrically with a fiberoptic catheter in the central venous location. MEASUREMENTS: Aortic blood pressure and central venous oxygen saturation were simultaneously measured throughout each resuscitation. Return of spontaneous circulation was defined as a systolic blood pressure of more than 60 mm Hg for more than five minutes. RESULTS: One hundred patients who experienced 68 episodes of cardiac arrest were studied. Patients with return of spontaneous circulation had a higher initial and statistically higher mean and maximal central venous oxygen saturation than those without return of spontaneous circulation (P = .23, .0001, and .0001, respectively; P less than .05 is significant). No patient attained return of spontaneous circulation without reaching a central venous oxygen saturation of at least 30%. Only one of 68 episodes of return of spontaneous circulation was attained without reaching a central venous oxygen saturation of at least 40%. A central venous oxygen saturation of greater than 72% was 100% predictive of return of spontaneous circulation. CONCLUSION: Continuous central venous oxygen saturation monitoring can serve as a reliable indicator of return of spontaneous circulation during CPR in human beings. PMID- 1514721 TI - The epidemiology of cardiac arrest in young adults. AB - STUDY OBJECTIVE: To describe the epidemiology of cardiac arrest in young adults and to determine if there are characteristics unique to this group in terms of etiology, rhythm, and outcome. DESIGN: Retrospective, case review. SETTING: King County, Washington. TYPE OF PARTICIPANTS: All out-of-hospital victims of cardiac arrest who received emergency aid. MEASUREMENTS: The etiology, cardiac rhythm, and outcome were identified for each case. MAIN RESULTS: During the 13-year period from 1976 to 1989, there were 8,054 cardiac arrests; 252 of these were among young adults 18 to 35 years of age. Of those 252 cases, 61 (24%) were caused by ischemic heart disease, and 60 (24%) were caused by overdose. Asystole was the most common rhythm (48%), followed by ventricular fibrillation or tachycardia (31%). Long-term survival following these rhythms was 4% and 28%, respectively. In terms of age, etiology, and rhythm, young adults appear to represent a transitional group between children and older adults. There were no unique characteristics specific to young adults. Long-term survival is dependent more on rhythm than on age. CONCLUSION: In terms of age, etiology, and rhythm, young adults appear to represent a transitional group between children and older adults. PMID- 1514722 TI - Improving the time to thrombolytic therapy for myocardial infarction by using a quality assurance audit. AB - STUDY OBJECTIVE: To evaluate a program designed to improve the speed of delivery of thrombolytic therapy for myocardial infarction in an emergency department. DESIGN: Time to administer thrombolytic therapy was evaluated retrospectively in 1988. Then after physician and nurse education, time to therapy was audited in 1989 and 1990, with feedback to physicians. SETTING: A community hospital ED. PARTICIPANTS: Eight board-certified emergency physicians were monitored in their treatment of 58 patients. INTERVENTIONS: After the 1988 audit, the results for each physician were made known. Physician and nurse education was undertaken, and it was agreed to continue the audit. Nurses were encouraged to order ECGs rapidly, physicians were encouraged to make the treatment decision before consulting private physicians, and a goal of therapy in less than one hour was established. Further feedback on times was given to the physicians in 1989. MEASUREMENTS AND MAIN RESULTS: Mean time from ED arrival to thrombolytic therapy was 63 minutes in 1988, 47 minutes in 1989, and 38 minutes in 1990. This fall in time was significant (P = .0002). The number of patients treated within one hour rose from 45% in 1988 to 67% in 1989 and to 96% in 1990. CONCLUSION: Auditing time to thrombolytic therapy, combined with physician and nurse education and increased experience, can significantly improve the time to administration of thrombolytic therapy. PMID- 1514723 TI - A trial of nebulized magnesium sulfate to reverse bronchospasm in asthmatic patients. AB - STUDY OBJECTIVE: To test the hypothesis that nebulized magnesium sulfate reverses methacholine-induced bronchospasm in asthmatic patients. DESIGN: Randomized, double-blind, crossover clinical trial. SETTING: Center for Asthma and Allergic Diseases, Children's Hospital of Pittsburgh. TYPE OF PARTICIPANTS: Ten patients who were 21 to 37 years old and had stable asthma. INTERVENTIONS: Patients withheld asthma medications for 24 hours before each study day. Patients with baseline forced expiratory volume in one second (FEV1) of less than 80% were excluded. All subjects underwent bronchial methacholine challenge to produce bronchospasm. They then received one of three different nebulized treatments: 2.5 mg albuterol in 3 mL saline, 3 mL magnesium sulfate (268 mmol/L, pH 6.4), or 3 mL normal saline. Patients repeated spirometry 15 minutes after completing the study drug and then received albuterol by metered-dose inhaler. Spirometry was repeated after the metered-dose inhaler. Each patient made three separate visits to receive each of the three medications. MEASUREMENTS AND RESULTS: Methacholine reduced each patient's FEV1 by at least 20% at each testing session. Post methacholine treatment with nebulized albuterol improved FEV1 by a mean of 56% (SD, 19.6%). Nebulized normal saline led to a mean increase in FEV1 of 29% (SD, 26.5%). Nebulized magnesium sulfate improved FEV1 by a mean of 12% (SD, 12.0%) (P = .054 by paired t-test compared with normal saline). CONCLUSION: Nebulized magnesium sulfate has a minimal bronchodilatory effect in asthmatic patients with methacholine-induced bronchoconstriction. Responsiveness to magnesium sulfate may be dependent on the mechanism of induction of bronchospasm, and there probably is no role for nebulized magnesium sulfate in the treatment of acute bronchospasm due to cholinergic stimulation. PMID- 1514725 TI - The perfect resuscitation. PMID- 1514724 TI - Ketorolac versus meperidine and hydroxyzine in the treatment of acute migraine headache: a randomized, prospective, double-blind trial. AB - STUDY OBJECTIVE: To compare the effectiveness of IM ketorolac with that of meperidine and hydroxyzine in the treatment of acute migraine headache. DESIGN: Prospective, randomized, double-blind trial. SETTING: Urban emergency department with an annual census of 42,000 patients. PARTICIPANTS: Forty-seven adult patients with migraines enrolled on 50 visits. INTERVENTIONS: Patients were randomly assigned to receive a single injection of either 60 mg ketorolac (group 1) or 100 mg meperidine and 50 mg hydroxyzine (group 2). Pain assessment was made using both visual-analog and verbal descriptor scales. RESULTS: At 60 minutes, 15 patients (60%) from group 1 (25) and 14 patients (56%) from group 2 (25) reported a great deal of complete relief (P = .77) Sixty-minute mean pain relief scores (3.35 versus 3.37) were different (P = .76). Nine patients (36%) from group 1 and seven patients (28%) from group 2 required additional analgesia (P = .76). CONCLUSION: Ketorolac is as effective as meperidine and hydroxyzine for the treatment of acute migraine headache. PMID- 1514726 TI - Establishing standards for emergency cardiac care: a recognized role for emergency physicians. PMID- 1514727 TI - Comparison of intravenous and intranasal administration of epinephrine during CPR in a canine model. AB - STUDY OBJECTIVES: Epinephrine improves coronary perfusion pressure during CPR. However, administration of epinephrine during CPR may be delayed or omitted if IV or endotracheal access is not established. Therefore, the objective of this study was to determine if intranasal administration of epinephrine during CPR would provide an alternate route of drug administration that is readily accessible and requires no special technical skills. DESIGN AND SETTING: Randomized blinded study performed in a controlled laboratory environment. TYPE OF PARTICIPANTS: Twenty mongrel dogs weighing 19.5 +/- 4.6 kg. INTERVENTIONS: All dogs received either IV epinephrine 0.015 mg/kg or intranasal epinephrine 14 mg per nostril. Phentolamine (5 mg per nostril) was administered intranasally one minute before nasal administration of epinephrine to improve absorption. Each dog underwent three minutes of ventricular fibrillation followed by seven minutes of CPR with a pneumatic chest compression device. Epinephrine was administered at two minutes into CPR. MEASUREMENTS AND MAIN RESULTS: Seven dogs were excluded because of inadequate baseline coronary perfusion pressure or compression device displacement, leaving a total of 13 dogs for analysis (six IV epinephrine, seven intranasal epinephrine). Baseline coronary perfusion pressure (mean +/- SD) was similar for IV epinephrine and intranasal epinephrine (16.9 +/- 7.1 mm Hg versus 18.2 +/- 13.8 mm Hg, respectively, P = .84). For IV and intranasal epinephrine, coronary perfusion pressure increased to 21.4 +/- 9.2 mm Hg and 24.4 +/- 18.7 mm Hg one minute after epinephrine, respectively (P = .73). Five minutes after epinephrine coronary perfusion pressure was 18.2 +/- 8.7 mm Hg and 24.3 +/- 13.9 mm Hg for IV epinephrine and intranasal epinephrine, respectively (P = .38). The rate of successful resuscitation was similar for both groups, five of seven dogs for intranasal epinephrine and four of six dogs for IV epinephrine (P = .66). CONCLUSION: Intranasal epinephrine has similar effects on coronary perfusion pressure and resuscitation compared with standard-dose IV epinephrine. Therefore, the nasal route for administration of epinephrine appears to be an acceptable alternate method of drug delivery during CPR and compares favorably with standard IV therapy in the canine model. Because of the obvious benefits to human patients, these observations suggest further investigation. PMID- 1514728 TI - Correlation of end-tidal CO2 to cerebral perfusion during CPR. AB - STUDY OBJECTIVE: A number of studies have demonstrated a correlation between end tidal carbon dioxide (ETCO2), cardiac output, and return of spontaneous circulation in experimental animals and in patients undergoing closed-chest CPR. Our study attempted to correlate ETCO2 to cerebral blood flow during cardiac arrest. DESIGN: Sixteen piglets were anesthetized, intubated, and instrumented for cerebral blood flow studies. An ultrasonic flow probe was placed on both internal carotid arteries for continuous flow measurements. The animal was fibrillated, and closed-chest CPR was begun. Continuous ETCO2 measurements were obtained and compared with simultaneous internal carotid, cardiac output, and cerebral blood flow measurements. MEASUREMENTS AND MAIN RESULTS: Correlations between ETCO2 and carotid and cerebral blood flow were determined using Pearson's method. The correlation between ETCO2 and total internal carotid flow was .58 (P = .01, Bonferroni's adjusted P = .30). Correlation between ETCO2 and cerebral blood flow was .64 (P = .01, Bonferroni's adjusted P = .09). A partial correlation coefficient for ETCO2 versus cardiac output was .70, whereas it was only .30 for ETCO2 versus cerebral blood flow. CONCLUSION: Partial correlation coefficients suggest that ETCO2 correlates with cerebral blood flow when changes in cerebral blood flow parallel changes in cardiac output. PMID- 1514730 TI - The use of animals for research in emergency medicine. Society for Academic Emergency Medicine. PMID- 1514729 TI - Evaluation of the Q.E.D. Saliva Alcohol Test: a new, rapid, accurate device for measuring ethanol in saliva. AB - STUDY OBJECTIVE: To evaluate the accuracy of the Q.E.D. A-150 Saliva Alcohol Test, a new device that gives a specific quantitative blood alcohol level by measuring saliva alcohol concentration in the range of 0 to 150 mg/dL. STUDY DESIGN: Forty-two healthy volunteers consumed 4.5 to 6 oz of alcohol in the form of beer, wine, or liquor over a 90-minute period. Blood and saliva samples were obtained for alcohol measurement at 30, 60, 90, and 120 minutes after the last drink. Blood samples were analyzed within 24 hours by gas chromatography at a commercial clinical laboratory. Saliva samples were tested immediately using the new Q.E.D. A-150 Saliva Alcohol Test. RESULTS: Excellent correlation was observed between saliva and blood alcohol levels over the range of 0 to 150 mg/dL (slope = 1.0; intercept = 2.4; r = .98). CONCLUSION: The Q.E.D. Test is an accurate device for specific quantitative measurement of alcohol levels using saliva. PMID- 1514731 TI - Emergency department presentation and care of heart and heart/lung transplant recipients. AB - STUDY OBJECTIVE: Heart and heart/lung transplants are accepted forms of therapy for patients with end-stage cardiac or pulmonary disease. These patients are likely to present postoperatively to the emergency department. To our knowledge, there have been no previous reports in the medical literature of the ED presentation of these patients. DESIGN: We conducted a retrospective review of the records of all patients who had received a heart or a heart/lung transplant at Stanford University Medical Center from 1988 through 1990 and who had at least one ED visit. MEASUREMENTS AND RESULTS: Between the time of operation and April 1, 1991, 131 ED visits were recorded. Fever was the single most common presenting complaint, for 48 (37%) of the visits. Difficulty in breathing (13%); gastrointestinal symptoms of nausea, vomiting, or diarrhea (10%); and chest pain (9%) were other common reasons for presentation. CONCLUSION: The transplant patient, by virtue of requiring chronic immunosuppression, is susceptible to infection with a spectrum of opportunistic organisms. When fever or other symptoms suggest infection, appropriate cultures and aggressive diagnostic procedures (eg, lumbar puncture, bronchoscopy) should be performed. PMID- 1514732 TI - Abrupt onset of weakness and seizure in a 39-year-old woman. PMID- 1514733 TI - Loiasis: a case of an unusual ocular foreign body. AB - Loiasis is a parasitic illness that is endemic in parts of Central and West Africa. In the United States, infection with Loa loa is seen in natives from that region of Africa and in those who have traveled to the area, often in the distant past. There can be significant differences in clinical manifestations between the two groups. We present a case of loiasis in an African native as well as a discussion of Loa loa infection in natives and non-natives and current treatment strategies. PMID- 1514734 TI - Volar metacarpal phalangeal joint dislocation: a rare and often missed injury. AB - Volar metacarpal phalangeal joint dislocations are rare injuries. We could find only eight cases reported, with none in the emergency medicine literature. We present a case report and describe the biomechanics and radiographic findings of this injury. PMID- 1514735 TI - Ruptured splenic abscess secondary to infectious mononucleosis. AB - A 24-year-old woman with a recent diagnosis of infectious mononucleosis presented with fever and left upper quadrant pain. Abdominal computed tomography revealed a splenic abscess that at laparotomy was found to have ruptured. This case illustrates a rare cause of splenic abscess and a rare complication of infectious mononucleosis. PMID- 1514736 TI - Decision making in patients with suspected AMI. PMID- 1514737 TI - Adequate training for endotracheal intubation. PMID- 1514738 TI - Augmented carotid massage. PMID- 1514739 TI - Flea collar pupil. PMID- 1514740 TI - Comparison of laser trabeculostimulation with laser trabeculoplasty in open-angle glaucoma. AB - We compared a new method, laser trabeculostimulation (LTS), with laser trabeculoplasty (LTP). The technique LTS stimulates trabecular meshwork tissue and thereby increases the outflow facility. The method LTP causes shrinkage and cicatrization of the meshwork tissue, thus limiting the reduction in postoperative intraocular pressure (IOP). The mean preoperative IOP of 40 eyes was 24.9 +/- 6.8 mmHg (mean +/- standard deviation). The LTS was applied with a 50-microns spot size, a power setting of 50mW, and an exposure time of 1 sec. With LTS, the IOP decreased and then increased afterward. Low power (50mW) was effective if used for a longer duration. The LTS can be applied repeatedly and used in addition to conventional LTP. The overall effect achieved with LTS was less than that with LTP, but it is possible to reduce IOP by selecting more reasonable parameters, e.g., a laser setting of 200mW, a 50 microns spot size and a 0.5 to 1-sec duration. PMID- 1514741 TI - Efficacy of cryotherapy in vernal catarrh. AB - Cryotherapy of the palpebral conjunctiva with oral aspirin has been evaluated in mixed-type active vernal keratoconjunctivitis. The symptoms and signs were recorded on a four-point scale. In 15 patients, we used cryotherapy of the palpebral conjunctiva in 30 eyes (-60 degrees C to -80 degrees C for 30 seconds, repeating the freeze-thaw cycle 2-3 times). All patients received oral aspirin 0.5 to 1.5 g in three divided doses daily over six weeks. The relief from symptoms was statistically significant (P less than .001). Objective improvement (palpebral and bulbar signs) also was statistically significant (P less than .001). Follow-up of these cases for one year showed a 3.3% recurrence rate. PMID- 1514742 TI - Continuous control of intraocular pressure in pseudophakic retinal detachment surgery. AB - We describe a method for continuous control of intraocular pressure in pseudophakic retinal detachment surgery done shortly after extracapsular cataract extraction and posterior chamber intraocular lens implantation. The system consists of a special needle inserted into the anterior chamber through the corneal limbus. The needle is attached by a regular intravenous administration set to an infusion bag. This allows fluids to exit the eye when the eyeball is compressed and to return to the eye when pressure on the eye is released. The presence of an intact posterior capsule and an intraocular lens do not impose a significant barrier to the passage of fluids between the anterior chamber and the vitreous cavity. Using this technique, intraocular pressure can be stabilized throughout the operation. The implementation of this system is demonstrated by a case report. PMID- 1514743 TI - Dislocation of the crystalline lens in a patient with Sturge-Weber syndrome. AB - A moderately retarded institutionalized patient diagnosed with Sturge-Weber syndrome and bilateral retinitis pigmentosa underwent enucleation OD because of intractable pain secondary to glaucoma in 1965. Twenty-three years later, the patient had a dislocated lens OS. Although the lens dislocation might have been caused by trauma, it also might be associated with either Sturge-Weber syndrome or retinitis pigmentosa. The role of protective eye wear in one-eyed institutionalized retarded patients is discussed. To our knowledge, this combination of Sturge-Weber syndrome, bilateral retinitis pigmentosa, and a dislocated lens has not been reported previously. PMID- 1514744 TI - Acute monocular blindness secondary to fibrous dysplasia of the skull: a case report. AB - An unusual case of acute monocular visual loss secondary to fibrous dysplasia is presented. Orbital and optic canal decompression restored vision completely. A review of the pertinent literature revealed that operative intervention may be curative in patients with acute monocular visual loss. This finding contrasts with the chronic visual decline found secondary to fibrous dysplasia of the skull. PMID- 1514745 TI - Eales disease with internuclear ophthalmoplegia. AB - Eales disease is an idiopathic type of retinal perivasculitis characterized by recurrent retinal and vitreous hemorrhages. Neurologic involvement is rare. We report the case of a patient with Eales disease who had internuclear ophthalmoplegia thought to be a neurologic manifestation of this disease. PMID- 1514746 TI - Transient fluorescein leakage simulating subretinal membrane: a diagnostic dilemma. AB - A 68-year-old woman with blurred vision had a foveal spot of fluorescein leakage that later was found to be a transient leakage. The clinical picture resembled central serous chorioretinopathy, a rare diagnosis in older patients. Other possible diagnoses (e.g., subretinal neovascular membrane or epiretinal membrane) are discussed as is the need for laser treatment. PMID- 1514747 TI - Retinal circulation in primary open-angle glaucoma tested by videodensitometric image analysis. AB - To investigate the retinal circulation in primary open-angle glaucoma (POAG), we used videodensitometric image analysis of fluorescein angiography to calculate the build-up time, the time constant of the washout rate, and the mean circulation time (MCT) in both the retinal artery and vein. We found the MCT in the POAG group (23 eyes of 20 patients) was significantly longer than in the normal group (3.7 +/- 2.0 sec and 2.8 +/- 1.7 sec, respectively; P less than .05). It correlated significantly with the vertical cup-to-disc ratio (r = .32; P less than .01), the outflow facility (r = -.35, P less than .005), and the glaucomatous visual-field loss. There was no correlation between MCT and intraocular pressure tested at the same time (r = .09, not significant). Therefore, treatment to decrease the intraocular pressure may not be associated directly with improved retinal circulation. PMID- 1514748 TI - Forty questions in otolaryngology (suggestion box for young investigators). 1951. PMID- 1514749 TI - Phonation and swallowing considerations in pediatric laryngotracheal reconstruction. AB - Experience with laryngotracheal reconstruction (LTR) has resulted in and continues to yield modifications and refinements in approach and technique with the goal to restore and maintain total laryngeal function. In addition to airway obstruction, the laryngeal functions of phonation and swallowing also may be affected by the underlying injury as well as by procedures designed to enlarge the airway. This paper discusses various problems encountered with phonation and swallowing in pediatric patients who underwent LTR and postoperative patients who were seen during the year July 1, 1990, through June 30, 1991. Phonation problems became apparent as long-term difficulties that persisted after tracheotomy decannulation. Swallowing was frequently a short-term perioperative problem while a stent was in place following LTR. The approaches and techniques that have been employed to treat, minimize, and prevent these problems are discussed. PMID- 1514750 TI - Consumer product aspiration and ingestion in children: analysis of emergency room reports to the National Electronic Injury Surveillance System. AB - Inadvertent aspiration or ingestion of products in children is a reportable problem. The National Electronic Injury Surveillance System (NEISS) monitors 119 hospitals for product (nonfood) hazards through a network of emergency room physicians. Coins (52%) remain the most frequently ingested object (1988-1989). Pins, including nails and bolts, are second in rank. Spheres (eg, balls) are the most common cause of death. Most deaths (97%) occur in the home. Younger children (13.4 versus 22.7 months) are more at risk for death. This analysis suggests that shape, as well as availability, is important in children's injuries and deaths. Accurate reporting to NEISS of all aspirated objects remains essential so that product safety and the public's health can be improved. Food product injuries, however, are not reported to NEISS. PMID- 1514751 TI - Pediatric airway manifestations of gastroesophageal reflux. AB - Gastroesophageal reflux (GER) in children may be classified as physiologic or pathologic, depending on its degree and consequences. There are many head and neck complications of GER in pediatric patients, but most numerous are the airway manifestations, including stridor, recurrent croup, exacerbation of subglottic stenosis, laryngeal irritation with or without laryngospasm, chronic cough, and obstructive apnea. Diagnosis may be difficult unless there is a high index of suspicion for GER and awareness of the concept of "silent" GER. We present the common pediatric airway manifestations of GER, illustrated by case reports, and provide a paradigm to assist in the diagnosis and management of children with airway compromise associated with GER. PMID- 1514752 TI - Distributions of eustachian tube goblet cells and glands in children with and without otitis media. AB - The distributions of the goblet cells and submucosal glands in eustachian tubes (ETs) from children with or without otitis media (OM) were studied. From 12 temporal bone-ET specimens obtained from children 1 to 7 years old at death, representative vertically cut histology sections were selected, stained with periodic acid-Schiff-Alcian blue and hematoxylin, and studied by light microscopy. In children without OM, the density of the goblet cells was significantly lower in the roof than in the floor of the ET and was highest in the midcartilaginous portion; glands were most richly distributed near the pharyngeal orifice, and became less densely distributed toward the tympanic portion. In children with OM, the density of the goblet cells was significantly higher both in the roof and floor portions, and the glands were more richly distributed than in the ETs of children without OM. The possibility that the observed increase in ET secretory components in children with OM impairs the passage of air through these tubes is discussed. PMID- 1514753 TI - Fascia and perichondrium atrophy in tympanoplasty and recurrent middle ear atelectasis. AB - Fascia and perichondrium grafts to replace and reinforce thin, atrophic tympanic membranes (TMs) are recommended by several authors to correct middle ear atelectasis by forming a fibrous, collapse-resistant TM. This study reviewed the status of connective tissue grafts performed over the 10-year period from 1979 to 1988 to determine if these grafts would maintain sufficient strength and fibrous character to resist recurrent atelectasis. The author used fascia or perichondrium to repair 89 TM defects, and 63 ears were available for follow-up: 54 had cholesteatomas and 9 had perforations. Graft atrophy was judged by microscopic otoscopy and Kodachrome otophotography. Fascia TM grafts atrophied in 35 of 43 ears (80%), and perichondrium atrophied in 8 of 20 ears (40%). Grafts maintained their relatively thick and fibrous character in only 20 of 63 ears (32%). If fascia and perichondrium used to correct atelectasis were to atrophy at the same rate as the grafts in this series, atelectasis would recur after attempts to reinforce atrophic TMs. Atelectasis-prone middle ears require intubation despite surgery. PMID- 1514754 TI - Clearance function of eustachian tube and negative middle ear pressure. AB - Two experimental studies were performed using 18 cats in order to elucidate the mechanism of the long-lasting course of otitis media with effusion. First, the middle ear (ME) pressure was monitored for 2.5 to 7 hours after filling the whole ME space with saline. On average, -150 mm H2O of negative ME pressure was induced in 3.1 hours. Second, the residual volume of saline with antibiotics, which was put into the ME space 2 to 7 days before, was compared between the side on which tubal ventilatory function was abolished (resection of tensor veli palatini muscle and hamulus pterygoideus) and the opposite, control side. The percentage of the residual volume to the original volume put into the ME was significantly higher on the experimental side (Wilcoxon's ranking test, t = 27.0, p less than .05), and in one ear on the experimental side, the ME pressure showed-150 mm H2O just before the bulla was opened 2 to 7 days later. These results seem to indicate that tubal ciliary clearance function can induce negative ME pressure when there is fluid in the ME, and that the negative ME pressure induced by clearance of the ME fluid may disturb further clearance of the ME fluid. This condition may cause the long-lasting course of otitis media with effusion. PMID- 1514755 TI - Chondroblastoma of the temporal bone. Case report and literature review. AB - Chondroblastoma is a rare tumor of bone that represents approximately 1% of all primary bone tumors. In the temporal bone, only 33 have been reported. We present a case of chondroblastoma of the temporal bone, followed by a literature review and analysis of reported cases. We conclude that the best chance for a prolonged disease-free interval is total excision using a combined otolaryngologic and neurosurgical approach. PMID- 1514756 TI - Organ-limited laryngeal amyloid deposits: clinical, morphological, and immunohistochemical results of five cases. AB - Five cases of organ-limited laryngeal amyloid deposits with no evidence of systemic disease are reported in detail and classified immunohistochemically. In four of the five cases the amyloid reacted with anti-A lambda antibodies and in one case with anti-A kappa antibodies. Four of our five female patients had already passed the fifth decade of life. One was 11 years old. Hoarseness was the predominant symptom in four cases, in which we found amyloid deposits in the glottic area. Only one patient, with amyloid deposits in the aryepiglottic fold, complained of pain. The therapy of choice of idiopathic, localized, or organ limited amyloid deposits without underlying disease may be local excision. In one of the cases reported in this paper, a laryngofissure was performed, and in another a partial laser resection was performed. No therapy was performed in three of our five cases. In the larynx, as in many other locations and only if possible, removal at intervals is more feasible than radical resection, because these amyloid tumors grow slowly. PMID- 1514757 TI - New device for interdental immobilization. AB - The immobilization of a simple fractured jaw with arch bars is a time-consuming, laborious procedure. The alternative method of immobilization described here uses a precisely threaded, 22-gauge, malleable stainless steel wire and a threaded nylon nut. It affords the surgeon relative safety from accidental puncture trauma and makes the interdental immobilization a precise and speedy procedure. PMID- 1514758 TI - Computer recognition of brain stem auditory evoked potential wave V by a neural network. AB - A neural network simulator was used for the recognition of the presence and location of the peak of wave V of the brain stem auditory evoked potential (BAEP) test. Waveforms selected from BAEPs performed in the last 4 years at the University of Pittsburgh Presbyterian University Hospital were digitized and sampled, and the resulting amplitudes were normalized. A training set was composed of the waveforms resulting from the stimulation of 50 ears. The normalized amplitudes were used as the initial activation values for the networks. The desired outputs (the target locations for wave V) were represented in the output layer by setting the output element, which corresponded to the target location and its immediate neighbors, to high activation levels, and all the remaining output units to zero activity. Two network architectures, differing only in the hidden unit layer, with 40 and 16 hidden units, respectively, were trained by using standard back-propagation. Several trials from different starting points were performed for each architecture. The best network, found after 60 epochs (3,000 presentations), was able to correctly identify 17 of 20 cases (85%) from a set of test cases that were independent from the training set. PMID- 1514759 TI - Intraparotid hematoma. PMID- 1514760 TI - Amyloidosis in the upper aerodigestive tracts. AB - The upper aerodigestive tracts, particularly the larynx, are not uncommon repositories for amyloid. In most instances amyloidosis of the larynx is localized and is not associated with or followed by systemic disease. Oral and nasopharyngeal amyloidoses, on the other hand, are very often manifestations of systemic predisposing disorders. Laryngeal amyloidosis is treated, when indicated, by surgical removal, often repeated because of persistence or multifocal deposits. PMID- 1514761 TI - Rosai-Dorfman disease involving the premaxilla. PMID- 1514762 TI - Thyroid paraganglioma. PMID- 1514763 TI - [Chronic pancreatitis in Cameroon. Analysis of etiological and clinical aspects]. AB - In a collection of 3,571 patient's files admitted in the University Teaching Hospital and the Yaounde General Hospital, we studied 27 patients suspected of chronic pancreatitis. 20 patients with calcified chronic pancreatitis benefited from a detailed history, physical examination and a complete paraclinical work up. From the data collected, chronic alcoholism seemed to have been the main aetiology. Industrial beer from barley alone and/or associated with other traditional liquors was most consumed. The majority of patients were heavy alcoholics and daily consumption varied from 75 to 124 g of pure alcohol. The natural history of the disease and physical examination were identical to that observed in the western countries. Associated pathology was observed in 10% of the patients. This included peptic ulcer disease, cirrhosis and bile stones. Complications included diabetics, obstructive jaundice, and malabsorption syndrome. As a conclusion, chronic pancreatitis is a pathology whose prevalence seems to be progressing constantly. PMID- 1514764 TI - [Difficult diagnosis of a biliary cyst. A case report]. AB - A 26 year-old man presented a hepatic cyst complicated by intracystic bleeding. Clinical and biological features (chronic pancreatitis), ultrasound and computed tomography findings apparent hepatic and splenic location), macroscopic aspects (inflammatory changes, brown-colored fluid) as well as microscopic characteristics (thickened cyst-wall, absence of epithelium) of both cysts suggested the diagnosis of pancreatic pseudocysts. The diagnosis of hepatic cyst was carried out on histological examination showing Meyenburg and neuro-fibrillar complexes. Occurrence of complications (bleeding, size enlargement) may modify typical histological aspect of hepatic cyst. PMID- 1514765 TI - [A case of acute cardiac insufficiency caused by 5-fluorouracil]. AB - The authors report a case of acute cardiac failure linked to 5 fluoro-uracil. The toxicity seen most commonly involves ischemia. The pathophysiological mechanisms are discussed as well as the role played by pharmacokinetic characteristics in the occurrence of adverse reactions. 5 fluoro-uracil (5 FU) is a compound widely used in the treatment of ENT, breast and gastrointestinal carcinomas. The finding of dose-effect relationship may lead the clinician to use different modes of administration. Continuous administration at high dose 3 g/m2/day from D1 to D5) in combination or not with cisplatin, or continuously at low dose (300 mg/m2/day from D1 to D31) can reduce hematopoietic toxicity but, in contrast, increases gastrointestinal toxicity. PMID- 1514766 TI - [Viral B hepatopathies and liver transplantation. The risk of graft infection]. PMID- 1514767 TI - [Anal and perianal manifestations in infection by the human immunodeficiency virus]. PMID- 1514768 TI - [An acute hepatic attack after taking an anti-arrhythmic]. PMID- 1514769 TI - [Sigmoid diverticular diseases: surgical treatment]. AB - From 1966 to 1990, 226 consecutive patients were operated on electively for diverticular disease of the sigmoid colon. The indications for surgery were colovesical fistula or suspicion of residual abscess, existence of two or more previous attacks of acute inflammation, existence of chronic symptoms and suspicion of colonic carcinoma. Colonic resection with primary anastomosis was performed in 217 patients with a covering colostomy in 1 case only. The Hartmann procedure was performed in 9 patients with extension of the lesions to the rectum and/or high operative risk. One or more abscesses were found by the surgeon or the pathologist in 50 p. cent of the patients. There were no postoperative deaths, no clinical anastomotic leakages. Long-term results were evaluated for the patients operated on before 1987, with a follow-up from 2 to 22 years. 85 p. cent of the patients had no more symptoms, 11 p. cent complained of persistent symptoms and 3% had recurrent attacks of pain and fever. Colonic barium enema is the best examination for diverticulitis and chronic abscesses. Surgical treatment is easier for abscesses located within the colonic wall and mesentery, than for extracolic abscesses with local peritonitis. Correlations between preoperative symptoms and operative findings are often not good. The good results obtained in 82 p. cent of the patients operated on for chronic symptoms suggest that chronic symptoms should be part of the indications for elective surgery. The low incidence (3 p. cent) of recurrent attacks of pain and fever is in favour of a resection limited to the sigmoid colon even when diffuse colonic diverticula are present.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1514770 TI - [New research techniques in human nutrition]. AB - Accurate determination of energy requirement and nutrients metabolism is essential to improve physiological knowledge and for physiopathological purpose in human nutrition. This evaluation is an absolute necessity for food industry. Energy expenditure could be precisely determined by indirect calorimetry or doubly labeled water technic. Nutrients metabolism and substrates turn-over studies are now accessible without health hazard using tracers labelled with stable isotopes. These three methods are the basic tools for the new Research Nutrition Center which are now in progress. PMID- 1514771 TI - Selective culture of mitotically active human Schwann cells from adult sural nerves. AB - We devised a simple method to isolate mitotically active human Schwann cells from sural nerve biopsy specimens and expand the population in culture. Nerve fascicles were treated with cholera toxin for 7 days in culture before dissociation, which increased the cell yield at least twenty-five-fold over immediated tissue dissociation. Digesting the tissue completely with enzymes in serum-containing medium resulted in the highest cell viability, and released 2 to 6 x 10(4) cells/mg of tissue. Seeding the cells on a poly-L-lysine substrate in a small volume of serum-free medium optimized the plating efficiency. Although Schwann cells comprised 90% of the initial culture population, their numbers declined over time due to a faster mitotic rate of the fibroblasts in the presence of cholera toxin alone. However, treating the cultures with a combination of cholera toxin and forskolin, which act synergistically to elevate cyclic AMP levels, inhibited fibroblast growth without causing Schwann cell toxicity. Adding glial growth factor to the adenyl cyclase activators maximized Schwann cell proliferation, and the population rapidly and selectively expanded. Therefore, it should be possible to generate large numbers of Schwann cells from diseased nerves to study defects in cell function or from normal nerves to study the effects of Schwann cell grafts on neuronal regeneration. PMID- 1514772 TI - Recurrent status epilepticus in children. AB - Status epilepticus is an uncommon but life-threatening seizure. Little is known about the risk of recurrent status epilepticus in patients who present with an initial episode. To determine the risk of recurrent status epilepticus in children, we prospectively followed 95 children, identified at the time of their first episode of status epilepticus, for a mean of 29.0 months (range, 4-60 months). The patients' ages ranged from 1 month to 18 years (mean, 4.6 years). The cause of the status epilepticus was classified as idiopathic (n = 24), remote symptomatic (n = 18), febrile (n = 29), acute symptomatic (n = 18), or progressive neurological disorder (n = 6). Sixteen children (17%) had at least 2 episodes of status epilepticus. The risk of recurrent status was 4% (n = 1) in the idiopathic group, 44% (n = 8) in the remote symptomatic group, 3% (n = 1) in the febrile group, 11% (n = 2) in the acute symptomatic group, and 67% (n = 4) in those with progressive neurological disease. Recurrent status epilepticus occurred primarily in neurologically abnormal children. While neurologically abnormal children accounted for 34% (n = 32) of all children with status epilepticus, they comprised 88% (n = 14) of the children with recurrent status epilepticus (p less than 0.001) and all 5 of the children with multiple (greater than or equal to 3) episodes of status (p less than 0.001). Fifteen of 16 children with recurrent status epilepticus were being treated with antiepileptic drugs at the time of recurrence. The morbidity and mortality of status epilepticus were low.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1514773 TI - Motion-defined letter detection and recognition in patients with multiple sclerosis. AB - Two important distinctions in visual perception are (1) between the detection and recognition of shape (e.g., letters), and (2) between the recognition of shapes defined by a difference in brightness and the recognition of shapes defined by a difference in motion. We report that 6 of 10 patients with multiple sclerosis showed impaired recognition for motion-defined (MD) letters, although the detection of MD letters was normal as were both detection and recognition of luminance-defined letters. We have shown that this was not a function of acuity loss or the loss of ability to detect motion or a general failure of recognition per se, but was confined to a loss of ability to recognize MD letters. The neurological implications of these findings are discussed, and it is suggested that the MD letter test be used by others interested in the central pathology of visual disorders. PMID- 1514774 TI - Quantitative magnetic resonance imaging in temporal lobe epilepsy: relationship to neuropathology and neuropsychological function. AB - Magnetic resonance images (MRIs) were obtained from 25 patients with medically refractory epilepsy of temporal lobe origin (12 on the left, 13 on the right) and 14 right-handed control subjects. The hippocampi and temporal lobes were traced by computer on successive coronal images and the resulting measurements of area were summed for each region. The left and right hippocampi were symmetrical in the control subjects; however, for patients the hippocampus was smaller on the side of the seizure focus. Moreover, the left-right hippocampal ratio significantly differentiated the control subjects from each patient group. The left temporal lobe was significantly smaller than the right in control subjects. The epileptics' temporal lobes were smaller on the side of the seizure focus, compared to the temporal lobes in the control subjects. MRI hippocampal measurements were compared to hippocampal neuronal densities obtained postoperatively. Significant correlations were obtained between the ratio (side ipsilateral to focus/side contralateral to focus) of MRI hippocampal measurements and neuronal densities in all hippocampal subfields except CA2. Prior to surgery, patients were administered the Wechsler Memory Scale and the verbal Selective Reminding Test. Significant correlations existed between MRI measurements of the left hippocampus and the Wechsler logical memory percent retention scores and between the left temporal lobe measurements and the verbal Selective Reminding Test scores for patients with seizure foci in the left temporal lobe. PMID- 1514776 TI - Neurological complications following liver transplantation. AB - Neurological complications occurred in 4 (19%) of 21 consecutive patients (Group II) undergoing orthotopic liver transplantation, compared with a 47% (9/19) incidence in our initial series (Group I). In Group II, the neurological problems included new recurrent headaches and delayed intracerebral hemorrhage (1 patient), partial third nerve palsy and brachial plexopathy (1 patient), and ataxic dysarthria with encephalopathy (2 patients). Seizures, noted in 8 of 9 neurologically affected Group I patients, were not encountered in Group II. Of the 4 patients in the entire series with the cerebrocerebellar syndrome, 2 had partial recovery after stopping treatment with cyclosporine, 1 stabilized when cyclosporine was discontinued but later worsened when rechallenged, and 1 had full recovery but died following a second transplantation. Brain magnetic resonance images appeared normal in 3 of the 4 patients. Complications affecting vision included cortical blindness in 2 patients and occipital lobe hemorrhage in 1. All completely recovered. Survival was comparable for patients with and those without neurological complications (69% and 63%, respectively). Immediate withdrawal of cyclosporine at the onset of a change in mental status or dysarthria and improvement in intra- and postoperative management may have contributed to the decreased incidence of neurological complications. PMID- 1514775 TI - 3-O-methyldopa administration does not alter fluorodopa transport into the brain. AB - To determine if 3-O-methyldopa (3OMD) significantly inhibits the transport of 6 [18F]fluorodopa (6-FD) into the brain at the concentration normally encountered during L-dopa administration, we performed 6-FD studies with positron emission tomography in cynomolgus monkeys in the presence and absence of 3OMD. Infusion of 3OMD was designed to produce plasma concentrations equivalent to those seen in patients on chronic L-dopa therapy. Plasma 3OMD levels of 39 +/- 4 microM did not alter the blood-brain transfer rate of 6-FD. 6-FD positron emission tomographic studies in parkinsonian patients will therefore not be altered by 3OMD present in the blood in those patients taking L-dopa preparations. These results do not support the hypothesis that transport of L-dopa into the brain is inhibited by 3OMD to cause the declining response seen in patients with advanced Parkinson's disease. PMID- 1514777 TI - Functional neuroimaging strategy in temporal lobe epilepsy: a comparative study of 18FDG-PET and 99mTc-HMPAO-SPECT. AB - We performed 99mTc-hexamethylpropyleneamineoxime-single-photon emission computed tomography (SPECT) and 18F-fluorodeoxyglucose-positron emission tomography (PET) in 20 epileptic patients with well-lateralized temporal electroencephalographic focus, normal computed tomographic scan, and brain magnetic resonance imaging (MRI) either normal (n = 10) or showing nonspecific changes in the epileptogenic temporal lobe (n = 10). In patients with a normal MRI, PET exhibited focal hypometabolism in 80%, whereas SPECT showed corresponding hypoperfusion in only 20%. In patients with an abnormal MRI, PET and SPECT yielded 100% and 90% sensitivity, respectively. The metabolic and regional cerebral blood flow disturbances were topographically concordant with electroencephalographic and MRI findings in all these patients. Only patients with a large and pronounced hypometabolism on PET images exhibited hypoperfusion on SPECT. Spatial resolution appeared to be the critical factor responsible for the higher sensitivity of PET. However, this superiority of PET did not prove clinically useful in patients whose SPECT was abnormal, particularly when brain MRI showed nonspecific changes in the epileptogenic temporal lobe. PMID- 1514778 TI - New horizons in neurology. The twentieth century. AB - Neurology in the twentieth century has undergone extraordinary change, particularly in the past 40 years. We trace the major trends, including the growth of the field, the technological advances, the revolution in neuroscience, the emergence of neurology as a free-standing specialty, the rise of child neurology, and the development of neurological subspecialization. Subsequent articles in this series will expand on these subjects. PMID- 1514779 TI - A novel point mutation in the mitochondrial tRNA(Leu)(UUR) gene in a family with mitochondrial myopathy. AB - A T-to-C transition mutation at nucleotide position 3,250 in the mitochondrial tRNA(Leu)(UUR) gene was present in a family with mitochondrial myopathy. Two of three muscle biopsies examined had complex I (NADH-ubiquinone oxidoreductase) deficiency. Heteroplasmy of wild and mutant mitochondrial DNA was detected by Nae I digestion of the polymerase chain reaction products with a modified primer. This was found in blood or muscle samples or both from all seven members examined. Similar to the 3,243 mutation in most patients with MELAS (mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes), the new mutation site was located in the dihydrouridine loop and embedded in the binding region of mitochondrial transcription termination factor. Elucidation of the effects of this mutation may help clarify the role of mitochondrial tRNAs and transcription termination. PMID- 1514780 TI - Idiopathic childhood stroke is associated with human leukocyte antigen (HLA)-B51. AB - We report four children with idiopathic stroke syndromes who were assayed for human leukocyte antigen (HLA) class I markers and found to have HLA-B51 in common. This finding suggests that there may be a genetic predisposition for "idiopathic" childhood stroke, and host factors, possibly in concert with environmental factors or viruses, may play a major role in the mechanism of unexplained occlusion of the cerebral vasculature in children. PMID- 1514781 TI - Serum IgG antibody to ganglioside GQ1b is a possible marker of Miller Fisher syndrome. AB - We studied serum anti-glycolipid antibodies by enzyme-linked immunosorbent assay and thin-layer chromatography-enzyme immunoassay in six consecutive patients with typical Miller Fisher syndrome. In all six, increased activity of IgG antibody against ganglioside GQ1b was present in the early phase and reduced with time, whereas such activity was not detected in normal control subjects and disease control subjects including those with Guillain-Barre syndrome. Anti-GQ1b IgG antibody is a new possible diagnostic marker of Miller Fisher syndrome and could well be related to the disease process itself. PMID- 1514782 TI - Undetectable tumor necrosis factor-alpha in spinal fluid from HIV-1-infected patients. PMID- 1514783 TI - Molecular cloning of the Clostridium botulinum structural gene encoding the type B neurotoxin and determination of its entire nucleotide sequence. AB - DNA fragments derived from the Clostridium botulinum type A neurotoxin (BoNT/A) gene (botA) were used in DNA-DNA hybridization reactions to derive a restriction map of the region of the C. botulinum type B strain Danish chromosome encoding botB. As the one probe encoded part of the BoNT/A heavy (H) chain and the other encoded part of the light (L) chain, the position and orientation of botB relative to this map were established. The temperature at which hybridization occurred indicated that a higher degree of DNA homology occurred between the two genes in the H-chain-encoding region. By using the derived restriction map data, a 2.1-kb BglII-XbaI fragment encoding the entire BoNT/B L chain and 108 amino acids of the H chain was cloned and characterized by nucleotide sequencing. A contiguous 1.8-kb XbaI fragment encoding a further 623 amino acids of the H chain was also cloned. The 3' end of the gene was obtained by cloning a 1.6-kb fragment amplified from genomic DNA by inverse polymerase chain reaction. Translation of the nucleotide sequence derived from all three clones demonstrated that BoNT/B was composed of 1,291 amino acids. Comparative alignment of its sequence with all currently characterized BoNTs (A, C, D, and E) and tetanus toxin (TeTx) showed that a wide variation in percent homology occurred dependent on which component of the dichain was compared. Thus, the L chain of BoNT/B exhibits the greatest degree of homology (50% identity) with the TeTx L chain, whereas its H chain is most homologous (48% identity) with the BoNT/A H chain. Overall, the six neurotoxins were shown to be composed of highly conserved amino acid domains interceded with amino acid tracts exhibiting little overall similarity. In total, 68 amino acids of an average of 442 are absolutely conserved between L chains and 110 of 845 amino acids are conserved between H chains. Conservation of Trp residues (one in the L chain and nine in the H chain) was particularly striking. The most divergent region corresponds to the extreme carboxy terminus of each toxin, which may reflect differences in specificity of binding to neurone acceptor sites. PMID- 1514784 TI - Cloning, expression, and nucleotide sequence of genes involved in production of pediocin PA-1, and bacteriocin from Pediococcus acidilactici PAC1.0. AB - The production of pediocin PA-1, a small heat-stable bacteriocin, is associated with the presence of the 9.4-kbp plasmid pSRQ11 in Pediococcus acidilactici PAC1.0. It was shown by subcloning of pSRQ11 in Escherichia coli cloning vectors that pediocin PA-1 is produced and, most probably, secreted by E. coli cells. Deletion analysis showed that a 5.6-kbp SalI-EcoRI fragment derived from pSRQ11 is required for pediocin PA-1 production. Nucleotide sequence analysis of this 5.6-kbp fragment indicated the presence of four clustered open reading frames (pedA, pedB, pedC, and pedD). The pedA gene encodes a 62-amino-acid precursor of pediocin PA-1, as the predicted amino acid residues 19 to 62 correspond entirely to the amino acid sequence of the purified pediocin PA-1. Introduction of a mutation in pedA resulted in a complete loss of pediocin production. The pedB and pedC genes, encoding proteins of 112 and 174 amino acid residues, respectively, are located directly downstream of the pediocin structural gene. Functions could not be assigned to their gene products; mutation analysis showed that the PedB protein is not involved in pediocin PA-1 production. The mutation analysis further revealed that the fourth gene, pedD, specifying a relatively large protein of 724 amino acids, is required for pediocin PA-1 production in E. coli. The predicted pedD protein shows strong similarities to several ATP-dependent transport proteins, including the E. coli hemolysin secretion protein HlyB and the ComA protein, which is required for competence induction for genetic transformation in Streptococcus pneumoniae.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1514785 TI - Nitrate and nitrite microgradients in barley rhizosphere as detected by a highly sensitive denitrification bioassay. AB - A highly sensitive denitrification bioassay was developed for detection of NO3- and NO2- in rhizosphere soil samples. Denitrifying Pseudomonas aeruginosa ON12 was grown anaerobically in citrate (30 mM) minimal medium with KClO3 (10 mM) and NaNO2 (3 mM), which gave cells capable of NO2- reduction to N2O but incapable of NO3- reduction to NO2-. Growth on citrate minimal medium further resulted in the absence of N2O reduction. When added to small soil samples in O2-free vials, such cells could be used to convert the indigenous NO2- pool to N2O, which was subsequently quantified by gas chromatography. Cells grown in KClO3-free citrate medium with 10 mM NaNO3 as the electron acceptor were capable of reducing both NO3- and NO2-, and these cells could subsequently be added to the sample to convert the indigenous NO3- pool to N2O. Concentrations of both NO3- and NO2- were thus determined as N2O, with a detection limit of approximately 10 pmol of N. The bioassay could be used to determine NO3- and NO2- pools in 10-mg soil samples taken along a microgradient in the rhizosphere of field-grown barley plants. At both low (10%, wt/wt) and high (18%, wt/wt) water content, relatively high levels of NO2- were found in the rhizosphere compared with bulk soil. Under dry conditions, NO3- was also more abundant in the rhizosphere than in the bulk soil, whereas such a difference was not observed at the high water content. The roles of plant metabolism and bacterial nitrification and denitrification processes for NO3- and NO2- availability in the rhizosphere are discussed. PMID- 1514786 TI - Characterization of bacteriocins from two strains of Bacillus thermoleovorans, a thermophilic hydrocarbon-utilizing species. AB - Bacillus thermoleovorans S-II and B. thermoleovorans NR-9 produce bacteriocins, and these bacteriocins are designated thermoleovorin-S2 and thermoleovorin-N9, respectively. The bacteriocins are effective against all but the producing strain of B. thermoleovorans, as well as being effective against Salmonella typhimurium, Branhamella catarrhalis, Streptococcus faecalis, and Thermus aquaticus. Thermoleovorins are produced during log-phase growth and are inhibitory to actively growing cells. The bacteriocins are proteinaceous in nature, being sensitive to selected proteases (protease type XI and pepsin). They are stable at pHs of 3 to 10. Thermoleovorin-S2 was more thermostable than thermoleovorin-N9 at 70 and 80 degrees C. Thermoleovorins-S2 and -N9 apparently act by binding to the susceptible organisms, resulting in lysis of the cell. Thermoleovorins-S2 has an estimated M(r) of 42,000, while thermoleovorin-N9 has a M(r) of 36,000. PMID- 1514787 TI - Degradation of azo dyes by the lignin-degrading fungus Phanerochaete chrysosporium. AB - Under nitrogen-limiting, secondary metabolic conditions, the white rot basidiomycete Phanerochaete chrysosporium extensively mineralized the specifically 14C-ring-labeled azo dyes 4-phenylazophenol, 4-phenylazo-2 methoxyphenol, Disperse Yellow 3 [2-(4'-acetamidophenylazo)-4-methylphenol], 4 phenylazoaniline, N,N-dimethyl-4-phenylazoaniline, Disperse Orange 3 [4-(4' nitrophenylazo)-aniline], and Solvent Yellow 14 (1-phenylazo-2-naphthol). Twelve days after addition to cultures, the dyes had been mineralized 23.1 to 48.1%. Aromatic rings with substituents such as hydroxyl, amino, acetamido, or nitro functions were mineralized to a greater extent than unsubstituted rings. Most of the dyes were degraded extensively only under nitrogen-limiting, ligninolytic conditions. However, 4-phenylazo-[U-14C]phenol and 4-phenylazo-[U-14C]2 methoxyphenol were mineralized to a lesser extent under nitrogen-sufficient, nonligninolytic conditions as well. These results suggest that P. chrysosporium has potential applications for the cleanup of textile mill effluents and for the bioremediation of dye-contaminated soil. PMID- 1514788 TI - Roles of manganese and organic acid chelators in regulating lignin degradation and biosynthesis of peroxidases by Phanerochaete chrysosporium. AB - We studied the effect of manganese and various organic chelators on the distribution, depolymerization, and mineralization of synthetic 14C-labeled lignins (DHP) in cultures of Phanerochaete chrysosporium. In the presence of high levels of manganese [Mn(II) or Mn(III)], along with a suitable chelator, lignin peroxidase (LiP) production was repressed and manganese peroxidase (MnP) production was stimulated. Even though partial lignin depolymerization was observed under these conditions, further depolymerization of the polymer to smaller compounds was more efficient when low levels of manganese were present. LiPs were prevalent under these latter conditions, but MnPs were also present. Mineralization was more efficient with low manganese. These studies indicate that MnP performs the initial steps of DHP depolymerization but that LiP is necessary for further degradation of the polymer to lower-molecular-weight products and mineralization. We also conclude that a soluble Mn(II)-Mn(III) organic acid complex is necessary to repress LiP. PMID- 1514789 TI - Moderation of ruminal fermentation by ciliated protozoa in cattle fed a high grain diet. AB - The objective of this study was to assess the influence of ciliated protozoa on ruminal fermentation in cattle fed high-grain diets. Six ruminally cannulated steers fed a corn-based grain diet (85% concentrate plus 15% alfalfa hay) at 12-h intervals were assigned randomly to two groups, ciliate free and faunated, in a crossover design. Defaunation was by ruminal emptying, omasal flushing, and treatment with sodium sulfosuccinate. Two to 3 weeks after defaunation, the ruminal contents of all steers were sampled before the morning feeding (0 h) and at 1, 2, 4, 6, 8, and 12 h after feeding to measure pH, analyze fermentation products, and monitor counts of ciliated protozoa and lactic acid-producing and fermenting bacterial groups. Total numbers of ciliated protozoa in the faunated steers averaged 4.3 x 10(5)/g, and the protozoa consisted of nine genera. Ciliate free steers had lower (P less than 0.01) ruminal pHs (pH 5.97) than faunated cattle (pH 6.45); however, the treatment-time interaction was not significant. Ruminal lactate and ammonia concentrations were similar in both groups. The total volatile fatty acid concentration was higher (P less than 0.05) in the ciliate free steers than in the faunated steers and exhibited a treatment-time interaction (P less than 0.05). The acetate-to-propionate ratio was higher (P less than 0.05) in the faunated group than in the ciliate-free group and showed a treatment-time interaction (P less than 0.05). Total anaerobic bacterial counts were about fourfold higher in the ciliate-free group than in the faunated group.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1514790 TI - Relationship between Legionella pneumophila and Acanthamoeba polyphaga: physiological status and susceptibility to chemical inactivation. AB - Survival studies were conducted on Legionella pneumophila cells that had been grown intracellularly in Acanthamoeba polyphaga and then exposed to polyhexamethylene biguanide (PHMB), benzisothiazolone (BIT), and 5-chloro-N methylisothiazolone (CMIT). Susceptibilities were also determined for L. pneumophila grown under iron-sufficient and iron-depleted conditions. BIT was relatively ineffective against cells grown under iron depletion; in contrast, iron-depleted conditions increased the susceptibilities of cells to PHMB and CMIT. The activities of all three biocides were greatly reduced against L. pneumophila grown in amoebae. PHMB (1 x MIC) gave 99.99% reductions in viability for cultures grown in broth within 6 h and no detectable survivors at 24 h but only 90 and 99.9% killing at 6 h and 24 h, respectively, for cells grown in amoebae. The antimicrobial properties of the three biocides against A. polyphaga were also determined. The majority of amoebae recovered from BIT treatment, but few, if any, survived CMIT treatment or exposure to PHMB. This study not only shows the profound effect that intra-amoebal growth has on the physiological status and antimicrobial susceptibility of L. pneumophila but also reveals PHMB to be a potential biocide for effective water treatment. In this respect, PHMB has significant activity, below its recommended use concentrations, against both the host amoeba and L. pneumophila. PMID- 1514791 TI - Sequence variation in the thermostable direct hemolysin-related hemolysin (trh) gene of Vibrio parahaemolyticus. AB - Our previous molecular epidemiologic study with gene probes (H. Shirai, H. Ito, T. Hirayama, Y. Nakamoto, N. Nakabayashi, K. Kumagai, Y. Takeda, and M. Nishibuchi, Infect. Immun. 58:3568-3573, 1990) demonstrated that the gene (trh) encoding a thermostable direct hemolysin-related hemolysin was strongly associated with clinical strains of Vibrio parahaemolyticus. Strain-to-strain variation in the intensities of the hybridization signals observed in the above study also suggested that the trh genes in different strains may have significantly divergent nucleotide sequences. To assess the public health significance of the rare environmental strains which exhibited very weak hybridization signals with the trh gene-specific DNA probe, the trh-like sequence was cloned from one of the environmental strains and the nucleotide sequence was determined in this study. A hemolysin gene (trh2) which was 84% homologous to the trh gene (newly named trh1) and 54.8 to 68.8% homologous to the genes (tdh) encoding thermostable direct hemolysins was detected in the cloned sequence. The trh2 gene product showed a profile of hemolytic activities against various animal erythrocytes different from that of the trh1 gene product. The trh2 gene product was antigenically related (partially identical) to the trh1 and tdh gene products. DNA colony blot and Southern blot hybridization analyses with trh1- and trh2-specific DNA probes showed that the trh1 probe-positive strains exhibiting hybridization signals with varying intensities could be clustered into trh1 and trh2 subgroups. In addition, hybridization analysis with oligonucleotide probes demonstrated significant strain-to-strain variation in the trh1 and trh2 gene sequences.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1514792 TI - Multiple periplasmic catalases in phytopathogenic strains of Pseudomonas syringae. AB - Phytopathogenic strains of Pseudomonas syringae are exposed to plant-produced, detrimental levels of hydrogen peroxide during invasion and colonization of host plant tissue. When P. syringae strains were investigated for their capacity to resist H2O2, they were found to contain 10- to 100-fold-higher levels of total catalase activity than selected strains belonging to nonpathogenic related taxa (Pseudomonas fluorescens and Pseudomonas putida) or Escherichia coli. Multiple catalase activities were identified in both periplasmic and cytoplasmic fluids of exponential- and stationary-phase P. syringae cells. Two of these activities were unique to the periplasm of P. syringae pv. glycinea. During the stationary growth phase, the specific activity of cytoplasmic catalases increased four- to eightfold. The specific activities of catalases in both fluids from exponential phase cells increased in response to treatment with 0.25 to 10 mM H2O2 but decreased when higher H2O2 concentrations were used. In stationary-growth phase cultures, the specific activities of cytoplasmic catalases increased remarkably after treatment with 0.25 to 50 mM H2O2. The growth of P. syringae into stationary phase and H2O2 treatment did not induce synthesis of additional catalase isozymes. Only the stationary-phase cultures of all of the P. syringae strains which we tested were capable of surviving high H2O2 stress at concentrations up to 50 mM. Our results are consistent with the involvement of multiple catalase isozymes in the reduction of oxidative stress during plant pathogenesis by these bacteria. PMID- 1514793 TI - Two types of bacterial alginate lyases. AB - The extracellular alginate lyases were purified from Vibrio harveyi AL-128 and V. alginolyticus ATCC 17749. The former enzyme appears to be specific for alpha-1,4 bonds involving L-guluronate units in alginate, whereas the latter exhibits specificity for beta-1,4 bonds involving D-mannuronate units. The molecular weights of the enzymes were estimated to be 57,000 and 47,000, and they had isoelectric points of 4.3 and 4.6, respectively. The enzyme from strain AL-128 was most active at NaCl concentrations of 0.3 to 1.0 M. Optimum activity of the enzyme from strain ATCC 17749 was found in the presence of 5 to 10 mM CaCl2. PMID- 1514794 TI - Characterization of Lactococcus lactis phage antigens. AB - Phage phi 197 is representative of a widespread lactococcal phage group characterized by a particular morphology (prolate head with a noncontractile tail). In order to develop an immunoenzymatic phage detection test, fusion proteins containing beta-galactosidase fused to epitopes of phage phi 197 structural proteins were constructed by cloning random DNA fragments from the phage genome upstream of a lacZ gene on a plasmid vector. Recombinant plasmids containing certain fragments encoded the synthesis of fusion proteins which react with polyclonal antibodies against the phage and confer a Lac+ phenotype on Escherichia coli. Three different epitopes were represented; phage-specific DNA fragments encoding these epitopes were mapped at three locations on the phage genome, and their nucleotide sequences were determined. Two fused phage antigens were conformational epitopes, whereas the phage epitope of protein encoded by the recombinant plasmid designated pOA17 was a denaturation-resistant epitope. This epitope was very immunogenic. Protein encoded by plasmid pOA17 was synthesized in large amounts from a strong promoter. Antibodies raised against this hybrid protein were used to identify the 46-kDa minor phage protein which provides the epitope. Antibody cross-reactivity of phages related to phi 197 showed that this epitope is well conserved in this genetic group. PMID- 1514795 TI - Reassessment of the prevalence of heat-stable enterotoxin (NAG-ST) among environmental Vibrio cholerae non-O1 strains isolated from Calcutta, India, by using a NAG-ST DNA probe. AB - A collection of 521 environmental isolates of Vibrio cholerae which were previously examined by the suckling mouse assay and found to be negative for the heat-stable enterotoxin NAG-ST were reassessed by a recently developed DNA probe for NAG-ST. A total of 12 (2.3%) of the isolates hybridized with the NAG-ST probe. By using a cholera toxin (CT) DNA probe, the CT gene was detected in six of the strains in the collection, although none of the isolates of V. cholerae non-O1 hybridized with both of the toxin probes. All of the NAG-ST and CT probe positive strains were hemolysin positive. Thirty-fold-concentrated supernatants of the three representative NAG-ST DNA probe-positive V. cholerae non-O1 strains gave positive fluid accumulation ratios in the suckling mouse assay even after heating (100 degrees C for 5 min) and also inhibited the binding of a NAG-ST monoclonal antibody to the bound NAG-ST in a competitive enzyme-linked immunosorbent assay (ELISA). Likewise, all six CT probe-positive V. cholerae non O1 strains produced in vitro CT when examined by the CT bead ELISA. HindIII digest patterns of chromosomal DNA from the representative NAG-ST gene-positive strains were visually indistinguishable. Between the groups of NAG-ST probe positive strains examined, there was a variation in the hybridizable fragments, with one group of strains exhibiting a hybridizable fragment similar to that of the NRT 36 reference strain; a smaller HindIII fragment hybridized with the NAG ST probe in the other group of strains.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1514796 TI - Isolation and characterization of a variety of microcystins from seven strains of the cyanobacterial genus Anabaena. AB - Hepatotoxins (microcystins) from seven freshwater Anabaena strains originating from three different Finnish lakes and one lake in Norway were isolated by high performance liquid chromatography and characterized by amino acid analysis and fast atom bombardment mass spectrometry. All strains produced three to seven different microcystins. A total of 17 different compounds were isolated, of which 8 were known microcystins. The known compounds identified from six strains were MCYST (microcystin)-LR, [D-Asp3]MCYST-LR, [Dha7]MCYST-LR, [D-Asp3,Dha7]MCYST-LR, MCYST-RR, [D-Asp3]MCYST-RR, [Dha7]MCYST-RR, and [D-Asp3,Dha7]MCYST-RR. With the exception of MCYST-LR and [D-Asp3]MCYST-LR, this is the first time that isolation of these toxins from Anabaena strains has been reported. Three of the strains produced one to three toxins as minor components which could not be identified. Anabaena sp. strain 66 produced four unidentified toxins. The other Anabaena strains always contained both MCYST-LR and MCYST-RR and/or their demethyl variants. Quantitative differences between toxins within and between strains were detected; at times MCYST-LR and at other times MCYST-RR or demethyl derivatives thereof were the most abundant toxins found in a strain. PMID- 1514797 TI - Lipoxygenase inhibitors shift the yeast/mycelium dimorphism in Ceratocystis ulmi. AB - The yeast-mycelium dimorphism in Ceratocystis ulmi, the causative agent of Dutch elm disease, was switched by gossypol, nordihydroguaiaretic acid, and propylgallate. In each case the mycelial form was converted to the yeast form. These compounds are recognized lipoxygenase inhibitors. Inhibitors of cyclooxygenase and thromboxane synthetase did not cause mycelia to shift to the yeast form. We suggest the following two-part hypothesis: (i) that lipoxygenase is a target for antifungal antibiotics and (ii) that many phytoalexins (antimicrobial compounds of plant origin) are targeted toward fungal lipoxygenases. In addition, in a study to determine potential lipoxygenase substrates, a fatty acid analysis indicated that C. ulmi conidiospores contained high levels of oleic, linoleic, and linolenic acids but no arachidonic acid. PMID- 1514798 TI - Nonspecific reactions of a commercial enzyme-linked immunosorbent assay kit (TECRA) for detection of staphylococcal enterotoxins in foods. AB - A staphylococcal enterotoxin visual immunoassay kit (TECRA) has recently become commercially available. Since the kit is an enzyme-linked immunosorbent assay system equipped with polyvalent antisera against staphylococcal enterotoxin types A to E (SEA to SEE) and the test is simple and rapid to perform (4 h), it has been widely used for screening purposes. In this study, the sensitivity of the kit for detection of SEA, SEB, and SEC in ham, cheese, and mushrooms was similar to those of kits based on an enzyme immunoassay and reversed passive latex agglutination: 0.75 to 1.0 ng of SEA per ml, 0.5 to 0.75 ng of SEB per ml, and 1.0 to 1.25 ng of SEC per ml. However, the TECRA kit showed nonspecific reactions with food samples contaminated by microorganisms other than Staphylococcus aureus, such as Enterobacter agglomerans, Enterobacter cloacae, Proteus mirabilis, Pseudomonas aeruginosa, and Serratia marcescens. The substance contributing to the false-positive results differed from true staphylococcal enterotoxins in that it was (i) heat labile (completely inactivated by heating for 2 min at 100 degrees C, whereas true staphylococcal enterotoxins were inactivated by about 10% with this treatment), (ii) lower in molecular weight than staphylococcal enterotoxins, and (iii) not bound to a copper chelate Sepharose gel (all of the substance remained in the unbound wash fraction, whereas staphylococcal enterotoxins were quantitatively bound to the gel). The problem of false-positive results with the TECRA kit could be resolved by heat treatment (2 min at 100 degrees C) or by cleanup procedures involving metal chelate affinity chromatography with copper chelate Sepharose for 4 h before use of the TECRA kit. PMID- 1514799 TI - Fate of Escherichia coli O157:H7 as affected by pH or sodium chloride and in fermented, dry sausage. AB - The influence of pH adjusted with lactic acid or HCl or sodium chloride concentration on survival or growth of Escherichia coli O157:H7 in Trypticase soy broth (TSB) was determined. Studies also determined the fate of E. coli O157:H7 during the production and storage of fermented, dry sausage. The organism grew in TSB containing less than or equal to 6.5% NaCl or at a pH of 4.5 to 9.0, adjusted with HCl. When TSB was acidified with lactic acid, the organism grew at pH 4.6 but not at pH 4.5. A commercial sausage batter inoculated with 4.8 x 10(4) E. coli O157:H7 per g was fermented to pH 4.8 and dried until the moisture/protein ratio was less than or equal to 1.9:1. The sausage chubs were then vacuum packaged and stored at 4 degrees C for 2 months. The organism survived but did not grow during fermentation, drying, or subsequent storage at 4 degrees C and decreased by about 2 log10 CFU/g by the end of storage. These studies reveal the importance of using beef containing low populations or no E. coli O157:H7 in sausage batter, because when initially present at 10(4) CFU/g, this organism can survive fermentation, drying, and storage of fermented sausage regardless of whether an added starter culture was used. PMID- 1514800 TI - Novel Bacillus thuringiensis insecticidal crystal protein with a silent activity against coleopteran larvae. AB - A novel Bacillus thuringiensis crystal protein with a silent activity against the Colorado potato beetle is described. The crystal proteins are produced as bipyramidal crystals. These crystals contain a protein of 129 kDa with a trypsin resistant core fragment of 72 kDa. Neither a spore-crystal mixture nor in vitro solubilized crystals are toxic to any of several Lepidoptera and Coleoptera species tested. In contrast, a trypsin-treated solution containing the 72-kDa tryptic core fragment of the protoxin is highly toxic to Colorado potato beetle larvae. The crystal protein-encoding gene was cloned and sequenced. The inferred amino acid sequence of the putative toxic fragment has 37, 32, and 33% homology to the CryIIIA, CryIIIB, and CryIIID toxins, respectively. Interestingly, the 501 C-terminal amino acids show 41 to 48% amino acid identity with corresponding C terminal amino acid sequences of other crystal proteins. Because of the toxicity of the fragment to the Colorado potato beetle and because of the distinct similarities of the toxic fragment with the other CryIII proteins, this gene was given a new subclass name (cryIIIC) within the CryIII class of coleopteran-active crystal proteins. CryIIIC represents the first example of a crystal protein with a silent activity towards coleopteran insect larvae. Natural CryIIIC crystals are not toxic. Toxicity is revealed only after an in vitro solubilization and activation step. PMID- 1514801 TI - Comparison of bioaerosol sampling methods in barns housing swine. AB - The air in livestock buildings contains bioaerosol levels that are sufficiently high to cause adverse health effects in animals and workers. These bioaerosols are complex mixtures of live and dead microorganisms and their products as well as other aeroallergens. The effectiveness of sampling methods used for quantifying the very high concentrations of microorganisms in these environments has not been well studied. To facilitate an accurate assessment of respiratory hazards from viable organisms in agricultural environments, three bioaerosol sampling methods were investigated: the Andersen microbial sampler method (AMS), the all-glass impinger method (AGI), and the Nuclepore filtration-elution method (NFE). These methods were studied in a parallel fashion in 24 swine confinement buildings. Measurements were taken in two seasons with three types of culture media in duplicate to assess total bacteria, gram-negative enteric bacteria, and total fungi. Methods were analyzed for the proportion of samples yielding data within the limits of detection, intraclass reliability, and correlation between methods. For sampling viable bacteria, the AMS had a poor data yield because of overloading and demonstrated weak correlation with the AGI. Conversely, the AGI and NFE gave sufficient numbers of valid data points (90%), yielded high intraclass reliabilities (alpha greater than or equal to 0.92), and were highly correlated with each other (r = 0.86). The AGI and the NFE were suitable methods for assessing bacteria in this environment, but the AMS was not. The AMS was the only method that consistently recovered enteric bacteria (73% data yield). For sampling fungi, the AGI and AMS both yielded sufficient data and all three methods demonstrated high intraclass reliability.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1514802 TI - Effects of antibacterial agents on in vitro ovine ruminal biotransformation of the hepatotoxic pyrrolizidine alkaloid jacobine. AB - Ingestion of pyrrolizidine alkaloids, naturally occurring plant toxins, causes illness and death in a number of animal species. Senecio jacobaea pyrrolizidine alkaloids cause significant economic losses due to livestock poisoning, particularly in the Pacific Northwest. Some sheep are resistant to pyrrolizidine alkaloid poisoning, because ovine ruminal biotransformation detoxifies free pyrrolizidine alkaloids in digesta. Antibacterial agents modify ruminal fermentation. Pretreatment with antibacterial agents may account for some animal variability in resistance to pyrrolizidine alkaloid toxicosis, and antibacterial agents can also be used for characterizing ruminal pyrrolizidine alkaloid biotransforming microflora. The objective of this study was to evaluate the effects of antibacterial agents on biotransformation of a predominant S. jacobaea pyrrolizidine alkaloid, jacobine, in ovine ruminal contents. Ovine ruminal jacobine biotransformation was tested in vitro with 20 independent antibacterial agents. Low amounts of rifampin and erythromycin prevented jacobine biotransformation. Chlortetracycline, lasalocid, monensin, penicillin G, and tetracycline were slightly less effective at inhibiting jacobine biotransformation. Bacitracin, crystal violet, kanamycin, and neomycin were moderately inhibitory against jacobine biotransformation. Brilliant green, chloramphenicol, gramicidin, nalidixic acid, polymyxin B SO4, sodium azide, streptomycin, sulfisoxazole, and vancomycin had little to no effect on jacobine biotransformation. The antibiotics that were most effective at inhibiting biotransformation were those that are active against gram-positive bacteria. Therefore, gram-positive bacteria are most likely critical members of the jacobine-biotransforming consortia. PMID- 1514803 TI - Contribution of anaerobic protozoa and methanogens to hindgut metabolic activities of the American cockroach, Periplaneta americana. AB - The ciliate Nyctotherus ovalis occurs in high numbers in the hindgut of the American cockroach (Periplaneta americana) and harbors methanogenic bacteria as endosymbionts. The contribution of these hindgut microorganisms to metabolic and developmental processes of P. americana was studied by comparing cultures of cockroaches in which the composition of the hindgut microbial population was altered in various ways. Rearing the insects protozoan free resulted in increased insect generation time, decreased adult body weight, and absence of methane production. After feeding of protozoan-free adult cockroaches with a hindgut suspension containing N. ovalis and methanogens, methane increased to normal values and insect body weight was restored during the development of the second generation of insects. Feeding the protozoan-free cockroaches a hindgut suspension which was made free of N. ovalis resulted in an increase in methane production to only about 20% of the normal methane production level. This suggests that the methanogenic endosymbionts of N. ovalis are the major source of methane production in the hindgut. Inhibition of methanogens by addition of bromoethanesulfonic acid to the drinking water of a normal cockroach culture resulted in a reduction of methane production to about 2% of the normal level. No effects on insect body weight or the number of N. ovalis organisms were observed, but the fermentation pattern in the hindgut was shifted towards a relative increase in propionate levels. Similar results were obtained for in vitro cultures of hindgut microorganisms treated with bromoethanesulfonic acid. The results suggest a major role for hindgut protozoa in cockroach metabolic activities, especially during the insect growth period. The relatively large amounts of methane produced by cockroaches and by other methane-producing xylophagous insects suggest a major contribution by insects to global methane production. PMID- 1514804 TI - Enumeration of phenanthrene-degrading bacteria by an overlayer technique and its use in evaluation of petroleum-contaminated sites. AB - Bacteria that are capable of degrading polycyclic aromatic hydrocarbons were enumerated by incorporating soil and water dilutions together with fine particles of phenanthrene, a polycyclic aromatic hydrocarbon, into an agarose overlayer and pouring the mixture over a mineral salts underlayer. The phenanthrene-degrading bacteria embedded in the overlayer were recognized by a halo of clearing in the opaque phenanthrene layer. Diesel fuel- or creosote-contaminated soil and water that were undergoing bioremediation contained 6 x 10(6) to 100 x 10(6) phenanthrene-degrading bacteria per g and ca. 5 x 10(5) phenanthrene-degrading bacteria per ml, respectively, whereas samples from untreated polluted sites contained substantially lower numbers. Unpolluted soil and water contained no detectable phenanthrene degraders (desert soil) or only very modest numbers of these organisms (garden soil, municipal reservoir water). PMID- 1514805 TI - Response surface analysis of the effects of pH and dilution rate on Ruminococcus flavefaciens FD-1 in cellulose-fed continuous culture. AB - The ruminal cellulolytic bacterium Ruminococcus flavefaciens FD-1 was grown in cellulose-fed continuous culture with 20 different combinations of pH and dilution rate (D); the combinations were selected according to the physiological pH range of the organism (6.0 to 7.1) and growth rate of the organism on cellulose (0.017 to 0.10 h-1). A response surface analysis was used to characterize the effects of pH and D on the extent of cellulose consumption, growth yield, soluble sugar concentration, and yields of fermentation products. The response surfaces indicate that pH and D coordinately affect cellulose digestion and growth yield in this organism. As expected, the net cellulose consumption increased with increasing D while the fraction of added cellulose that was utilized decreased with increasing D. The effect of changes in pH within the physiological range on cellulose consumption was smaller than that of changes in D. Cellulose degradation was less sensitive to low pH than to high pH. At low Ds (longer retention times), cellulose degradation did not follow first-order kinetics. This decreased rate of cellulose digestion was not due to poor mixing, limitation by other medium components, or preferential utilization of the more amorphous fraction of the cellulose. The cell yield increased from 0.13 to 0.18 mg of cells per mg of cellulose with increasing Ds from 0.02 to 0.06 h-1 and decreased when the pH was shifted from the optimum of 6.5 to 6.8. The effect of pH on cell yield increased with increasing D. The reduced cell yield at low pH appears to be due to both an increase in maintenance energy requirements and a decrease in true growth yield. PMID- 1514807 TI - Volatile metabolites produced by six fungal species compared with other indicators of fungal growth on cereal grains. AB - Six fungal species, Penicillium brevicompactum, P. glabrum, P. roqueforti, Aspergillus flavus, A. versicolor, and A. candidus, were inoculated on moistened and autoclaved wheat and oat grains. They were cultivated in glass vessels provided with an inlet and outlet for air. Air was passed through the vessels to collect volatile fungal metabolites on porous polymer adsorbents attached to the outlet. Samples were collected at two fungal growth stages. Adsorbed compounds were thermally desorbed, separated by gas chromatography, and identified by mass spectrometry. Differences in the production of volatile metabolites depended more on the fungal species than on the grain type. The fungal growth stage was not an important factor determining the composition of volatiles produced. 3-Methylfuran was produced in similar amounts regardless of the fungal species and substrate (oat versus wheat). The production of volatile metabolites was compared with the production of ergosterol and CO2 and the number of CFU. The production of volatile metabolites was more strongly correlated with accumulated CO2 production than with actual CO2 production and more strongly correlated with ergosterol contents of the grain than with numbers of CFU. PMID- 1514806 TI - Novel mutations in the pheA gene of Escherichia coli K-12 which result in highly feedback inhibition-resistant variants of chorismate mutase/prephenate dehydratase. AB - The bifunctional enzyme chorismate mutase/prephenate dehydratase (EC 5.4.99.5/4.2.1.51), which is encoded by the pheA gene of Escherichia coli K-12, is subject to strong feedback inhibition by L-phenylalanine. Inhibition of the prephenate dehydratase activity is almost complete at concentrations of L phenylalanine greater than 1 mM. The pheA gene was cloned, and the promoter region was modified to enable constitutive expression of the gene on plasmid pJN302. As a preliminary to sequence analysis, a small DNA insertion at codon 338 of the pheA gene unexpectedly resulted in a partial loss of prephenate dehydratase feedback inhibition. Four other mutations in the pheA gene were identified following nitrous acid treatment of pJN302 and selection of E. coli transformants that were resistant to the toxic phenylalanine analog beta-2 thienylalanine. Each of the four mutations was located within codons 304 to 310 of the pheA gene and generated either a substitution or an in-frame deletion. The mutations led to activation of both enzymatic activities at low phenylalanine concentrations, and three of the resulting enzyme variants displayed almost complete resistance to feedback inhibition of prephenate dehydratase by phenylalanine concentrations up to 200 mM. In all four cases the mutations mapped in a region of the enzyme that has not been implicated previously in feedback inhibition sensitivity of the enzyme. PMID- 1514808 TI - Contribution of phenazine antibiotic biosynthesis to the ecological competence of fluorescent pseudomonads in soil habitats. AB - Phenazine antibiotics produced by Pseudomonas fluorescens 2-79 and Pseudomonas aureofaciens 30-84, previously shown to be the principal factors enabling these bacteria to suppress take-all of wheat caused by Gaeumannomyces graminis var. tritici, also contribute to the ecological competence of these strains in soil and in the rhizosphere of wheat. Strains 2-79 and 30-84, their Tn5 mutants defective in phenazine production (Phz-), or the mutant strains genetically restored for phenazine production (Phz+) were introduced into Thatuna silt loam (TSL) or TSL amended with G. graminis var. tritici. Soils were planted with three or five successive 20-day plant-harvest cycles of wheat. Population sizes of Phz- derivatives declined more rapidly than did population sizes of the corresponding parental or restored Phz+ strains. Antibiotic biosynthesis was particularly critical to survival of these strains during the fourth and fifth cycles of wheat in the presence of G. graminis var. tritici and during all five cycles of wheat in the absence of take-all. In pasteurized TSL, a Phz- derivative of strain 30-84 colonized the rhizosphere of wheat to the same extent that the parental strain did. The results indicate that production of phenazine antibiotics by strains 2 79 and 30-84 can contribute to the ecological competence of these strains and that the reduced survival of the Phz- strains is due to a diminished ability to compete with the resident microflora. PMID- 1514809 TI - The homologous and heterologous regions within the iap gene allow genus- and species-specific identification of Listeria spp. by polymerase chain reaction. AB - The iap gene of Listeria species encodes protein p60. The comparison of iap related genes from different Listeria species indicated common and variable regions within these genes which appeared to be specific for each Listeria species. On the basis of the iap gene sequences, pairs of polymerase chain reaction (PCR) primers which allowed the unambiguous identification of all members of the genus Listeria, of groups of related Listeria species, and of L. monocytogenes, exclusively, were selected. The PCR primers specific for L. monocytogenes yielded PCR products which represented essentially the repeat region of the iap gene. The size of these PCR products allowed an estimate of the number of the TN repeat units within the repeat region of the p60 protein of an L. monocytogenes strain. The data indicated that the number of repeat units differed among L. monocytogenes isolates. PMID- 1514810 TI - Oxidation of nitrotoluenes by toluene dioxygenase: evidence for a monooxygenase reaction. AB - Pseudomonas putida F1 and Pseudomonas sp. strain JS150 initiate toluene degradation by incorporating molecular oxygen into the aromatic nucleus to form cis-1,2-dihydroxy-3-methylcyclohexa-3,5-diene. When toluene-grown cells were incubated with 2- and 3-nitrotoluene, the major products identified were 2- and 3 nitrobenzyl alcohol, respectively. The same cells oxidized 4-nitrotoluene to 2 methyl-5-nitrophenol and 3-methyl-6-nitrocatechol. Escherichia coli JM109(pDTG601), which contains the toluene dioxygenase genes from P. putida F1 under the control of the tac promoter, oxidized the isomeric nitrotoluenes to the same metabolites as those formed by P. putida F1 and Pseudomonas sp. strain JS150. These results extend the range of substrates known to be oxidized by this versatile enzyme and demonstrate for the first time that toluene dioxygenase can oxidize an aromatic methyl substituent. PMID- 1514811 TI - Impact of growth conditions on resistance of Klebsiella pneumoniae to chloramines. AB - The resistance of Klebsiella pneumoniae to inorganic monochloramine (1.5 mg/liter; 3:1 Cl2:N ratio, pH 8.0) was examined in relation to growth phase, temperature of growth, and growth under decreased nutrient conditions. Growth phase did not impact resistance to chloramines. Mid-exponential and stationary phase cells, grown in a yeast extract-based medium, had CT99 values and standard deviations of 4.8 +/- 0.1 and 4.6 +/- 0.2 mg.min/liter, respectively. Growth temperature did not alter chloramine resistance at short contact times. CT99 values of cells grown at 15 and 23 degrees C were 4.5 +/- 0.2 and 4.6 +/- 0.2 mg.min/liter, respectively. However, at longer contact times, CT99.99 values of cells grown at 15 and 23 degrees C were 14 and 8 mg.min/liter, respectively, suggesting a small resistant subpopulation for cells grown at the lower temperature. Growth under decreased nutrient conditions resulted in a concomitant increase in resistance to chloramines. When K. pneumoniae was grown in undiluted Ristroph medium and Ristroph medium diluted by 1:100 and 1:1,000, the CT99 values were 4.6 +/- 0.2, 9.6 +/- 0.4, and 24 +/- 7.0 mg.min/liter, respectively. These results indicate that nutrient availability has a greater impact than growth phase or growth temperature in promoting the resistance of K. pneumoniae to inorganic monochloramine. PMID- 1514812 TI - Growth-promoting effect of thermophilic fungi on the mycelium of the edible mushroom Agaricus bisporus. AB - The growth-promoting effect of the thermophilic fungus Scytalidium thermophilum in mushroom compost on the mycelium of the edible mushroom Agaricus bisporus was investigated. Results obtained by others were confirmed by showing that S. thermophilum leads to an increased hyphal extension rate of the mushroom mycelium. However, it was demonstrated that hyphal extension rates were not clearly related to mushroom biomass increase rates. A number of experiments pointed strongly towards CO2 as the determinant of hyphal extension rates. In compost, CO2 is produced mainly by thermophilic fungi. Several experiments did not reveal any other specific compound produced by S. thermophilum that increases the hyphal extension rate of the mushroom mycelium. PMID- 1514813 TI - Complete mineralization of benzene by aquifer microorganisms under strictly anaerobic conditions. AB - Benzene was mineralized to CO2 by aquifer-derived microorganisms under strictly anaerobic conditions. The degradation occurred in microcosms containing gasoline contaminated subsurface sediment from Seal Beach, California, and anaerobic, sulfide-reduced defined mineral medium supplemented with 20 mM sulfate. Benzene, at initial concentrations ranging from 40 to 200 microM, was depleted in all microcosms and more than 90% of 14C-labeled benzene was mineralized to 14CO2. PMID- 1514814 TI - Metabolism of 3-methylindole by a methanogenic consortium. AB - A methanogenic 3-methylindole (3-MI)-degrading consortium, enriched from wetland soil, completely mineralized 3-MI. Degradation proceeded through an initial hydroxylation reaction forming 3-methyloxindole. The consortium was unable to degrade oxindole or isatin, suggesting a new pathway for 3-MI fermentation. PMID- 1514815 TI - Culture and decontamination methods affecting enumeration of phages infecting Bacteroides fragilis in sewage. AB - A new medium has been adapted for the growth of Bacteroides fragilis so that its phages can be recovered from environmental samples, and its efficiency has been assessed. Polyvinylidene difluoride membranes allow significantly higher recoveries among different membrane filters used to decontaminate the samples. In all cases, a number of phages remain in the filters and a percentage of them can be recovered by treatment with an eluant. PMID- 1514817 TI - Development of the immunomagnetic enrichment method selective for Vibrio parahaemolyticus serotype K and its application to food poisoning study. AB - A method using immunomagnetic separation was developed to isolate the specified K serotype of Vibrio parahaemolyticus from a mixture of a large number of bacteria with other K serotypes. This method was applied to food poisoning studies and could recover the V. parahaemolyticus serotype found in the patient from the incriminated foods. PMID- 1514816 TI - Use of degenerate primers for polymerase chain reaction cloning and sequencing of the Lactococcus lactis subsp. lactis recA gene. AB - Two particularly well-conserved stretches in the RecA protein sequences were chosen as templates to synthesize degenerate oligonucleotides, which were used in polymerase chain reaction to amplify an internal recA DNA fragment of Lactococcus lactis subsp. lactis ML3. Using this fragment, we recovered and sequenced the entire lactococcal recA gene. The end of an open reading frame present upstream of the recA gene shows strong homology with formamidopyrimidine-DNA-glycosylase, a protein involved in DNA repair. PMID- 1514818 TI - Direct isolation of Yersinia pseudotuberculosis from fresh water in Japan. AB - Yersinia pseudotuberculosis was recovered from KOH-treated precipitates of 20.6% of 500 freshwater samples. KOH treatment of precipitates is a simple and expedient means of recovering Y. pseudotuberculosis from such samples. PMID- 1514819 TI - Use of inducible disaccharidases to assess the importance of different carbohydrate sources for Bacteroides ovatus growing in the intestinal tracts of germfree mice. AB - Patterns of disaccharidase expression were used to determine which polysaccharides were the major sources of carbohydrate for Bacteroides ovatus growing in the intestinal tracts of monocolonized germfree mice. Results indicate that B. ovatus grows on a variety of different carbohydrates, which are present in low concentrations, rather than relying on one type of carbohydrate as the major carbohydrate source. PMID- 1514820 TI - Temperature-dependent induction of an acid-inducible stimulon of Escherichia coli in broth. AB - The induction of the inducible lysyl-tRNA synthetase, LysU, and the inducible lysine and arginine decarboxylases of Escherichia coli K-12 grown in AC broth to a pH of 5.5 or less is temperature dependent, being distinctly lower at 24 than at 37 degrees C. This induction does not appear to be under HtpR control. PMID- 1514821 TI - Trends in cancer mortality, incidence and survival in Japan. AB - Cancer has been the leading cause of deaths since 1981 in Japan and is still on the increase accounting for 27% of all causes of deaths in 1989. The crude death rate of cancer has been increasing in both sexes, but the age-adjusted death rate has been stable in males and decreasing in females. Among various cancers cancers of the stomach, uterus, liver (females only), and esophagus (females only) have been decreasing. Leukemia and bladder cancer also tend to show a declining trend. Other cancers, especially cancers of the lung, colo-rectum, pancreas, biliary tract liver (males only), prostate, ovary, and breast are increasing in Japan. Trends in the cancer incidence are similar to those of cancer mortality. Causes of the marked secular trends in the cancer mortality and incidence are not clear, but the major causes are suspected to be changes in dietary habits, smoking and drinking habits, and other socio-environmental factors such as marital and reproductive factors. The five year survival rates of several cancers have been improved in the last decades. Thus, progresses in the diagnostic and therapeutic techniques and promotion of cancer screening may have also contributed to the decrease of cancer deaths. If the present trends in cancer mortality and incidence continue, cancer deaths/incidences will still increase and cancers of the lung, colo-rectum, liver (males only), pancreas, biliary tract, etc. will become major cancers in Japan in the future. To combat with ever increasing cancer it is necessary to further promote cancer research, cancer screening, programs for primary prevention of cancer, especially smoking control and improvement of dietary habits. PMID- 1514822 TI - Present status of cancer treatment in Korea. PMID- 1514823 TI - Current status of research on new anticancer drugs in China. PMID- 1514824 TI - Current cancer treatment in Hong Kong. PMID- 1514825 TI - Present status of cancer treatment in Taiwan. PMID- 1514826 TI - Present status of cancer treatment in Singapore-management of urological cancers. PMID- 1514827 TI - The facilities and challenges for cancer control in India. AB - India is a vast subcontinent with 845 million peoples occupying 2.5% of land mass of the earth, but carrying 15% of the world population. It is a multiracial society with widely varying cultures, habits, languages and many different ethnic groups. The pattern of cancer, therefore, mainly depends on their habits and life styles apart from other variations. Head, Neck & Esophagus cancers in the male and cervix and breast cancers in the females are the main cancers. All together they form nearly 60% of all cancers. The incidence rates are around 90/100,000 though this is an underestimate as cancer is not a notifiable disease in India. It is estimated that by the year 2,000 there will be six million cancer patients in India at any given time with nearly 2 million new patients annually. The over all facilities for cancer treatment vary widely from metropolitan cities to rural areas where 70% of the Indian population lives. In major cities, good to excellent treatment facilities exist in comprehensive cancer centres--yet in the rural setting the facilities are sketchy at best or non-existent at worst. The Government of India in its national cancer policy has recognized regional cancer centres and consolidated other existing centres. There are 10 regional cancer centres thus identified, each one at a different level of development. For optimal requirements at least 600 teletherapy units, (existing 150--not always functional) 100 departments of surgical oncology and an equal number of medical oncology divisions are needed (existing 20). The demand for cancer treatment facilities are, therefore, very high with poor available facility. Nearly 50% of patients present late for treatment and therefore appropriate education in prevention and early diagnosis are important factors. The Government of India through Ministry of Health has identified cancer as a major health problem by the year 2,000 and hence planning by the National Cancer Plan is operative in many States. Major cancer institutions (like the Tata Memorial Centre) have taken a lead to intensify the public and professional educational activities and have developed rural modules for primary and secondary prevention. The author exemplifies this by actual on the spot activities of the rural centre and stresses that in a country like India, the need is to develop small community cancer centres with the rural cancer effort as the base so as to reach out to the community for early diagnosis of treatment. PMID- 1514828 TI - Present status of cancer treatment in several Asian countries. AB - Most of Asian Countries are still developing. Hence there are constraints in cancer treatment. There are those countries with fully equipped and fully distributed like western world such as Japan, Korea and Singapore. Other with some comprehensive cancer centers but confine to only big cities with poor coverage of the population resulting in a lot of late cases of cancer patients seen. Such countries are Bangladesh, China, India, Indonesia, Malaysia, Sri Lanka, Thailand and etc. Still a lot of countries have no facilities to cope with cancer patients such as Brunei, Kampuchea, Laos, Nepal, Vietnam and etc. International collaboration and supports are needed. PMID- 1514829 TI - Endovesical instillation of mitomycin-C in preventing recurrence of superficial bladder carcinoma. AB - It is now clear that MMC can be used as endovesical instillation after TUR, partial cystectomy or transurethral laser treatment and at the same time it has chemo-resection and chemoprophylactic efficacy. The success of treatment seems out of question on dosage but with the continuation of the instillation program. Recently, we have adopted 20 mg per instillation once every week for 40 times in the first year and once for 2-4 weeks for the second year, the overall recurrent rate was 17%. Such dosage used is more better than 2 mg, 10 mg or even 40 mg with acceptable side effects. PMID- 1514830 TI - Present status of periampullary cancer treatment in Korea. AB - The incidence of periampullary cancer has been steadily risen in Korea. In the present study, we have reviewed 766 cases of surgically treated periampullary cancers, including 122 cases of our own, that were published in the Korean literatures in last ten years. The 6th decade was the most common age group, occupying 37.9% of the patients. Male to female, ratio was 1.7 to 1. C-T scan was the principal modality available for diagnosis and preoperative staging, and recorded 84% of diagnostic accuracy. The accuracy rate of PTC was 72%, ERCP of 68%, and USG of 51%, in order of frequency. For the screening of pancreatic cancer, diagnostic serologic test using serum markers such as CA 19-9, CEA, CA 125, and various combinations were studied. The combinations of these markers recorded higher positivity. Overall resectability was 36.2%. Preoperative C-T scan with antigraphy correlated with better discrimination of the resectable lesion preoperatively than C-T scan alone was performed (63% VS 46%). The morbidity and mortality after pancreaticoduodenectomy were 46% and 13.2%, and 1, 3, and 5-year survival rates after the resection were 68, 25, and 15%, respectively. In non-resected group, none survived at 18 months after treatment. To improve resectability; early detection, precise preoperative staging, and improved surgical approach are imperative. Future studies will be necessary to find a better multimodality therapy. PMID- 1514831 TI - Radical radiotherapy for carcinoma cervix--preliminary experience with the microSelectron high dose rate machine. AB - Radiotherapy for uterine cervix carcinoma is an accepted treatment for all stages of invasive malignancy. The radiation modality is usually a combination of brachytherapy and external beam therapy for all except the most extensive tumours (stage IV--FIGO). Satisfactory results have been obtained in the Singapore General Hospital using low dose-rate radium applications in combination with cobalt teletherapy. Five year actuarial survival rates of 86.7% were obtained for FIGO stage I, 65.0% for stage II, 41.4% for stage III, 4.9% for stage IV with an overall rate of 54.0% for all stages. Corresponding 10-year rates were: 79.6%, 60.2%, 35.2%, 0% and 48.2%. Preliminary results of primary radiotherapy in 36 patients with cervical carcinoma treated by high dose-rate brachytherapy (microSelectron HDR) combined with 6MVP photons from a Siemens linear accelerator are presented. The patients were registered at the Mount Elizabeth Oncology Centre from November 1989 to December 1990 inclusive. The morbidity from high dose-rate therapy appears lower (9.1% for vaginal stenosis, 6.1% for non-severe proctitis) than for the radium series (4.1% and 20.8%) although the major complication rate appears similar (3% vs 2.8% respectively). The total failure rate is also lower at 19.4% for the HDR patients compared to 33.5% for the radium group. However, these rates are not strictly comparable as the HDR series consists of a small number of patients with limited follow-up. In the light of the data indicating acceptable morbidity with significant rate of early failure, the HDR brachytherapy doses have been increased whilst keeping within the limits set by other centres. PMID- 1514832 TI - Allogeneic bone marrow transplantation for the patients with hemopoietic stem cell disorders: CUMC experience. AB - Bone marrow transplantation from an HLA-identical sibling is increasingly used as a curative therapy for patients with hemopoietic stem cell disorders including acute leukemia, chronic myelogenous leukemia and severe aplastic anemia. Between March 1983 and March 1991, we performed 86 cases of allogeneic bone marrow transplantation (BMT) for the patients with hemopoietic stem cell disorders: 25 acute myelogenous leukemia (AML); 15 acute lymphoblastic leukemia (ALL); 20 chronic myelogenous leukemia (CML); and 26 severe aplastic anemia (SAA). Ten out of 25 AML are in disease free survival (DFS). The causes of death were recurrence of leukemia (12), acute GVHD (3), sepsis (1) and veno-occlusive disease (1). Nine of 15 ALL are in unmaintained remission. Thirteen out of 20 CML are in DFS. Among 26 SAA, 21 are enjoying DFS, but 1 died of engraftment failure, 3 of graft rejection followed by cytomegalovirus (1) and aspergillus pneumonia (1). Comparing the survival between standard [less than or equal to CR1: 9/14 (64%)] and high risk [greater than or equal to CR1: 1/11 (9%)] AML, our data suggest that preparative regimen for high risk AML was not potent enough to eradicate the minimal residual disease in advanced AML. Although our cases are limited and the follow-up period is short, our result of ALL [overall: CCR (60%), standard risk (adult less than or equal to CR1, children less than or equal to CR2; 8/11 (73%) and high risk; 1/4 (25%)] and CML [overall: 65%, CP; 9/10 (90%), AP; 4/6 (67%), BP; 0/4 (0%)] are optimistic. It is of our interest that the incidence of death related with IP (1/33: 3%) and with AGVHD 94/33: 12%) were much less than that of other's observation but the explanation for this still remains to be clear. PMID- 1514833 TI - High dose mitomycin C for treatment of advanced gastric cancer. AB - Thirty five patients (26 males and 9 females) with advanced gastric cancer confirmed by pathology were treated by high-dose mitomycin C. According to the following dose and schedules: Mitomycin C 20 mg intravenously per week and a total of 60 mg. Three weeks later, all the patients received FT-207 600 mg daily and a total of 20-40 g. The ages ranged from 24 to 75 years, 11 had cancer of cardia, 6 had cancer of gastric body, and 18 had cancer of gastric antrum. Eleven patients could not have an operation. Seventeen patients were recurrence of post operation. Eighteen of 35 patients received CR (7/35) and PR (11/35), the response rate was 51.43% of the responders, the median duration of remission and survival were 7.3 (range, 2-16) and 12.2 (range, 3-30) months, respectively. Common doses were instilled. The main side effects were leukopenia (10/35) and thrombocytopenia (7/35). None of these patients had liver and kidney function damage. PMID- 1514834 TI - Analysis of one hundred and twenty five patients with primary liver cancer surviving more than five years. AB - During the period of 1958-1986, a series of 125 patients with pathologically proven hepatocellular carcinoma (HCC) surviving more than 5 years was collected in authors' institute. Thirty seven of them survived more than 10 years, the longest being 30 years. Of the entire series, 55.2% of patients was discovered by screening, 48.0% of patients was subclinical HCC, 80.0% of patients had solitary tumor, and 53.6% of patients had tumor size smaller than 5 cm. Pathological findings revealed that 90.2% of tumor was grade I and II (Edmondson grading) and 81.6% of patients associated with cirrhosis. The serum HBsAg was positive in 63% and anti-HBc in 80% of the patients who had checked the HBV markers. Of the 125 patients, 108 patients received resection, 67 patients were small HCC resection, 41 patients were non-small HCC resection, re-resection for subclinical recurrence or solitary lung metastasis was done in 26 patients with resection. Limited resection amounted to 54.6% of patients with resection. Of the 125 patients, 17 patients received palliative surgery other than resection, including hepatic artery ligation, cannulation, or their combination, etc. Eight out of the 17 patients received second stage resection due to marked shrinkage of tumor. It is concluded that early resection remained the major approach to get a long-term survivor, re-resection for subclinical recurrence is also of proved merit. Resection of huge tumor is still useful but less effective. Cyto-reduction and sequential resection is a new trend. Primary liver cancer (PLC) has long been recognized as incurable malignancy with extremely low 5-year survival rate. According to the cancer statistics in the United States, the relative 5-year survival rates for patients with PLC was 2% in 1960-1963, 3% in 1970-1973, 4% in 1974-1976, 3% in 1977-1980 and 5% in 1981-1986. Patients with PLC survived more than 5 years were rarely reported in the literature. In 1971, Curutchet collected worldwide data from 45 authors covering the period for 65 years (1905-1970), only 45 patients with PLC were found to be 5-year survivors. Thanks to the progress in tumor markers, particularly alpha fetoprotin (AFP) and new localization measurements, diagnosis and treatment are possible in subclinical stage. Based on combined strategies to the treatment of PLC including resection of small liver cancer, re-resection of subclinical recurrence after curative resection, multimodality treatment, and sequential resection after shrinkage of tumor, the 5 year survival of PLC has gradually increased.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1514835 TI - Chemotherapy of solid tumors in private practice in Malaysia. PMID- 1514836 TI - Primary chemotherapy for locally advanced uterine cervical carcinoma. AB - From September 1985 to May 1991, thirty consecutive patients with locally advanced cervical carcinoma stage IB-II (FIGO) with high risk factors of local treatment failure were treated with Epirubicin and Cisplatinum combination as primary chemotherapy. Twenty-five patients were evaluated for response, operability and survival. This combination chemotherapy could induce remarkable clinical complete response of 68% (17/25) and partial response of 28% (7/25), but only 18 patients were permitted for surgery, therefore operability rate was 72% (18/25). Pathological examination revealed complete response at 24% (6/25) and partial response was 48% (12/25) due to the presence of residual tumor at the cervix and dissected lymph nodes. The average number of lymph node dissected was II (range 0-26), which have been usually found in stage IIB-III patients. This combination chemotherapy did not allow to complicate surgery in these circumstances. Toxicities were mild except only leukopenia which was moderate to severe degree (WHO, grading). No death related to treatment has been found. The median time of follow up was 19 months (range 4-72), 24 patients still living, 22 without disease and 2 with diseases at the cervix and bone. The result of pilot study has suggested a beneficial role of primary chemotherapy in this type of malignancy. However, these data require further confirmation and longer follow up before a definite conclusion can be made regarding cure rate and prolong disease free-survival in locally-advanced uterine cervical carcinoma. PMID- 1514837 TI - Adjuvant chemotherapy and radiotherapy in the management of colorectal cancer. PMID- 1514838 TI - Chemotherapy for colorectal carcinoma. PMID- 1514839 TI - Interactive effects of selenium, methionine, and dietary protein on survival, growth, and physiology in mallard ducklings. AB - Concentrations of over 100 ppm (100 mg/kg) selenium (Se) have been found in aquatic food chains associated with irrigation drainwater. Both quantity and composition of dietary protein for wild ducklings may vary in selenium contaminated environments. Day-old mallard (Anas platyrhynchos) ducklings received one of the following diets containing 22% protein: unsupplemented (controls), 15 ppm Se (as selenomethionine), 60 ppm Se, methionine supplemented, 15 ppm Se with methionine supplement, or 60 ppm Se with methionine supplement. In a second concurrent experiment the above sequence was repeated with a protein restricted (11%) but isocaloric diet. In a third concurrent experiment all ducklings received 44% protein with 0, 15, or 60 ppm Se added. After 4 weeks, blood and tissue samples were collected for biochemical and histological examination. With 22% protein and 60 ppm Se in the diet, duckling survival and growth was reduced and histopathological lesions of the liver occurred. Antagonistic interactive effects occurred between supplementary methionine and Se, including complete to partial alleviation of the following Se effects by methionine: mortality, hepatic lesions, and altered glutathione and thiol status. With 11% protein, growth of controls was less than that with 22% protein, Se (60 ppm) caused 100% mortality, and methionine supplementation, although protective afforded less protection than it did with 22% protein. With 44% protein, ducklings experienced physiological stress, and Se was more toxic than with methionine-supplemented 22% protein. These findings suggest the potential for antagonistic effects of Se, methionine, and protein on duckling survival and physiology. PMID- 1514840 TI - Determination of textile dyes in organs of Oncorhynchus mykiss W. after in vitro exposure. AB - The quantitative determination in organs of Oncorhynchus mykiss W. of a premetallized dye (C.I. Acid Violet 66) and the azoic base (C.I. Acid Red 217), used in wool dyeing, is studied in this paper. UV-VIS Spectrophotometry was used for the chromatic quantification and atomic absorption spectrophotometry for the detection of the metal. The method described here is as satisfactory for the detection of some commercial dyes as the methods developed by ETAD (Ecological and Toxicological Association of the Dyestuffs Manufacturing Industry). PMID- 1514841 TI - Stainless steel cookware as a significant source of nickel, chromium, and iron. AB - Stainless steels are widely used materials in food preparation and in home and commercial cookware. Stainless is readily attacked by organic acids, particularly at cooking temperatures; hence iron, chromium, and nickel should be released from the material into the food. Nickel is implicated in numerous health problems, notably allergic contact dermatitis. Conversely, chromium and iron are essential nutrients for which stainless could be a useful source. Home cookware was examined by atomic absorption spectroscopy: seven different stainless utensils as well as cast iron, mild steel, aluminum and enamelled steel. The materials were exposed to mildly acidic conditions at boiling temperature. Nickel was a major corrosion product from stainless steel utensils; chromium and iron were also detected. It is recommended that nickel-sensitive patients switch to a material other than stainless, and that the stainless steel cookware industry seriously consider switching to a non-nickel formulation. PMID- 1514842 TI - Comparative teratogenicity of di-n-butyltin diacetate with n-butyltin trichloride in rats. AB - Teratological tests were conducted on di-n-butyltin diacetate (DBTA), and n butyltin trichloride (MBTC). Pregnant Wistar rats were treated orally with DBTA at doses of 0, 1.7, 5.0, 10.0, and 15.0 mg/kg/day or with MBTC at doses of 0, 50, 100, 200, and 400 mg/kg/day during days 7-17 of gestation. Cesarean sections were performed on day 20 of gestation. Thymic atrophy of the pregnant rats was observed in a dose-dependent manner by DBTA treatment. The incidence of dead or resorbed fetuses and total resorption fetuses increased at the highest dose of DBTA. The incidence of fetuses with external malformations, such as cleft mandible, cleft lower lip, ankyloglossia (tongue-tie) and schistoglossia (cleft tongue), increased in a dose-dependent manner by DBTA treatment. The incidence of fetuses with skeletal malformations such as anomaly of mandibular fixation, fused ribs, fused cervical vertebral arches and fused thoracic vertebral arches also increased at 10.0 and 15.0 mg/kg. However, MBTC, one of the main metabolites of di-n-butyltin, failed to show any evidence of tetatogenic activity at any doses tested. The results indicate that DBTA has potent teratogenic effects on rat fetuses, and DBTA is different from MBTC with respect to teratogenic effects. PMID- 1514843 TI - The influence of selected environmental parameters on the toxicity of Bayluscide to Schistosoma mansoni miracidia. AB - Laboratory studies were conducted to investigate the influence of selected environmental parameters on the toxicity of Bayluscide to Schistosoma mansoni miracidia. Test results indicated that temperature, pH, hardness and salinity of the water exerted profound effects on miracidial survival and that the miracidicidal action of bayluscide was highly influenced by these factors. In summary, this chemical was found to be more effective in killing the miracidia of S. mansoni in waters of higher temperatures, lower values of pH (acidic waters), lower degrees of hardness (soft waters) and lower levels of salt (freshwaters). The implications of such studies in the control of schistosomiasis transmission are addressed. PMID- 1514844 TI - Organochlorine pesticide contaminations in human milk samples from women living in Amman, Jordan. AB - Concentration of 15 organochlorine pesticides were determined by capillary gas chromatography in 59 human milk samples collected from the general population during 1989/1990 in the Jordanian capital of Amman. In addition to hexachlorbenzene (HCB), three groups of organochlorine compounds namely, DDT and its metabolites, hexachlorcyclohexane (HCH-isomers) and the cyclopentadiene group (aldrin, dieldrin, endrin, heptachlor, and heptachlor epoxide) were analyzed. The results show that almost all samples contained HCB, beta-HCH, p,p'-DDE and p,p' DDT, whereas p,p'-DDD, heptachlor, alpha-HCH, gamma-HCH and o,p'DDT were found in 42, 40, 33, 22 and 20 analyzed samples, respectively. The concentration of HCB, beta-HCH, p,p'-DDE, p,p'-DDT and heptachlor expressed on a milk-fat basis (median in mg/kg milk fat): 0.29, 0.4, 2.04, and 0.7 respectively. For the comparative purposes and in order to try to find the possible sources of mother-milk contaminations, different types of locally produced and imported cow milk samples were also analyzed for the same organochlorine compounds. Almost all types of tested milk were contaminated with p,p'-DDE. PMID- 1514845 TI - Ochratoxin A production in Bavarian cereal grains stored at 15 and 19% moisture content. AB - Wheat, barley, and maize, each in 15-kg parcels at 15 and 19% initial moisture content (IMC), were kept in a Bavarian farm granary from June through November 1990. During this period, the grain at each IMC was analyzed for mycotoxins and monitored for grain temperature, carbon dioxide, seed germination, and microfloral incidence and abundance. Barley and maize stored for 20 weeks at 19% IMC contained ochratoxin A in amounts of 70 and 90 microg/kg, respectively. This mycotoxin was not detected in wheat stored at 19% IMC, nor in the grains stored at 15% IMC. Aflatoxin B1, sterigmatocystin, citrinin, and zearalenone were also assayed but not detected in grains stored at either IMC. Principal component analysis of the data indicated that ochratoxin A was produced in a damp niche in maize, when abundant metabolic activity and CO2 production by Penicillium glandicola and Aspergillus spp. were common. PMID- 1514846 TI - [Various properties of erythromycin basicity]. AB - Erythromycin (Er) as a weak base showed some specific properties when dissolved in aqueous solutions. The basic ability of Er had a tendency to become weaker during storage in the room settings and especially at high temperatures. The temperature gradient within the ranges of 10 to 25 degrees C was dpH/dt = -0.03 (for 2 x 10(-3) M Er solution). However, the basic properties of the Er base partly renewed when Lewis' bases such as dimethyl carboxide, dimethylformamide and dimethyl sulfoxide were added to Er aqueous solutions previously stored for days or weeks. In chloroform solutions, either the thermodynamics or the kinetics of Er protonization showed no abnormalities as compared to nitric bases. It was supposed that in aqueous solutions of Er base there was transformation linked with intramolecular or extramolecular interactions which provoked shielding of the tertiary basic atom of nitrogen due to formation of the nitrogen linkage. PMID- 1514847 TI - [Ultrastructure of liposomes (interliposomal bonds)]. AB - Interliposomal bonds (ILBS) analogous to intercellular bonds (ICBs) in microbial cultures were detected by electron microscopy in the liposomal materials obtained after encapsulation of substances of various chemical structure. Possible nonspecific formation of the bonds between biological membrane-limited objects (ILBs and ICBs) was suggested and formation of such bonds in liposome encapsulated drugs was believed to be of importance. PMID- 1514848 TI - [Sensitivity of Shigella to antibiotics]. AB - Three hundred and twenty two Shigella cultures isolated from dysentery patients within 1986-1989 were tested with the use of standard paper disks for their sensitivity to levomycetin, streptomycin, tetracycline, monomycin, neomycin, kanamycin, erythromycin, gentamicin, carbenicillin, ampicillin, oxacillin, methicillin and doxycycline. The number of the cultures belonging to Shigella sonnei amounted to 85.1 per cent of the total number of the strains studied. 91.9, 89.5, 87.3, 87.3, 80.1 and 80.1 per cent of the cultures were sensitive to gentamicin, kanamycin, carbenicillin, neomycin, levomycetin and ampicillin, respectively. 99.4 per cent of the isolates were resistant to streptomycin and 97.2 per cent were resistant to tetracycline. The sensitivity to erythromycin remained rather high (70.2 per cent). The overwhelming majority of the Shigella sonnei isolates had multiple resistance. PMID- 1514849 TI - [Determining the sensitivity of anthrax bacteria to antibiotics for its differentiation from the antibiotic sensitivity of spore-forming saprophytes]. PMID- 1514850 TI - [Study of general toxic and organotropic properties of ampicillin combined with sulbactam]. AB - The effect of sulacillin, a combination of sulbactam and ampicillin (1:2), on the functions of the liver and kidneys, peripheral blood count, cardiovascular and central nervous systems was studied in acute and chronic experiments on animals of various species. The allergenic and local irritating properties of the combination were also studied. It was shown that the combination was low toxic and the interaction of sulbactam and ampicillin by the lethal effect was additive. When the combination was administered intravenously to mice, its LD50 amounted to 6 g/kg. In chronic experiments on rats parenterally given the combination in doses equivalent to the therapeutic ones there were no changes in the examined systems and organs. When used in the doses exceeding the therapeutic ones, sulacillin used during long periods induced a transitory elevation of blood levels of transaminases and alkaline phosphatases, an increase in the relative weight of the liver and kidneys, elongation the typhlon and an increase in glycogen levels in the hepatocytes without morphological changes. The combination had no significant effect of sulacillin and the painful injections alleviated by local anesthesia were recorded. The allergenic properties of the combination were moderate and did not differ from those of ampicillin. The data indicate that the combined sulacillin preparation greatly resembles its foreign analogue. PMID- 1514851 TI - [Multifactorial analysis of combined use of an antibiotic and peptidoglycan of microbial origin in experimental plague]. AB - The combined effect of doxycycline and microbial peptidoglycan was studied with multifactorial analysis. The drugs were used preventively and therapeutically. The preventive use of doxycycline in the subtherapeutic doses in combination with the immunomodulator resulted in a significant increase in the survival rate rather than the average life-span (ALS) of the experimental animals. The therapeutic use of the drugs was more efficient than the preventive one and resulted in higher survival and ALS. By the results of the experiments polynomial statistic models of the second order were developed and the equal level curves characterizing the survival rate and ALS were plotted. The dose-time regimens of the combined use of doxycycline an peptidoglycan were optimized. PMID- 1514852 TI - [Study of biosynthesis of mycoheptin, mycopentene and fatty acids by Streptoverticillium mycoheptinicum strain 255 in various conditions of its cultivation]. AB - The effect of the fat content in the medium for cultivation of Streptoverticillium mycoheptinium-255 and the effect of glucose intake on the rate of carbohydrate utilization and intensity of incorporation of labeled sodium acetate and propionate to mycoheptin, mycopentene and fatty acids were studied. It was shown that a lower fat content in the medium in comparison with the optimal one resulted in intensification carbohydrate catabolism during an idiophase, increased production rates of mycopentene, an accompanying antibiotic, and fatty acids and a decrease in the heptaene/pentaene ratio. The optimal contents of the oil in the medium provided a decrease in the rate of the carbohydrate consumption and preferable production of the required antibiotic or mycoheptin accompanied by a decrease in the synthesis rate of mycopentene and fatty acids. PMID- 1514853 TI - [Multifactor study of combined effects of an antibiotic and polysaccharide in experimental infection]. AB - Multifactorial analysis was applied to the study of the combined effect of doxycycline and a polysaccharide of microbial origin in experimental plague infection. A marked synergistic action of the antibiotic and polysaccharide used in subtherapeutic doses in treatment of the infection was observed. By the results of the experiments polynomial statistic models of the 2nd order were designed and nomographs or equal level lines were plotted. The models and nomographs described the animal survival rate and lifespan within a wide range of the control parameters. The dose/time regimens for the use of the polysaccharide combination with doxycycline were optimized on the basis of the multifactorial analysis. PMID- 1514854 TI - [Leukinferon in immunological correction of acute inflammatory diseases of the abdominal organs]. AB - Addition of (intramuscular+intravenous) leukinferon (LF) to the schemes for the treatment of acute peritonitis promoted a more rapid positive development of the time course of clinical signs and decreasing of leukocytosis in the presence of a pronounced tendency to normalization of the main immunological indices i. e. the counts of differential T-lymphocytes and T-helper cells. There was also activation of neutrophil phagocytic function. A rapid decrease in objective signs of endotoxicosis was recorded: the intoxication leukocytic index and the level of medium-mass molecules. In parallel with the decrease in the intoxication leukocytic index, there was a decrease in cytosis of the peritoneal exudate. The use of LF in the treatment of elderly patients with acute cholecystitis eliminated the clinical signs and normalized the main laboratory indices without surgical interventions which allowed one to make a planned operation with the minimum risk. PMID- 1514855 TI - [New methods of administration of cephalosporins and aminoglycosides: relations between pharmacokinetics and pharmacodynamics]. PMID- 1514856 TI - [Combined antibiotic preparations in veterinary medicine]. PMID- 1514857 TI - [Characteristics of obtaining protoplasts from 2 strains of Tolypocladium inflatum subsp. Blastosporum]. AB - The optimal conditions for preparing protoplasts with high yields by using the cells of two (low and high potent) isogenic cyclosporine-producing Tolypocladium strains were developed. A specific medium containing 0.5 per cent yeast autolysate (by dry weight) and 3 per cent glucose was used. When grown on this medium the cells of the highly potent strain 847 acquired a yeast-like shape. High yields of protoplasts prepared from the low potent strain 43 mycelium were obtained via prior incubation with 0.01 M dithiothreitol followed by treatment with a complex of enzymes from Helix pomatia for 1.5 to 2 hours was used. For preparation of the protoplasts with employing the highly potent strain 847 cells the prior incubation with dithiothreitol was not required, but it was necessary to employ a mixture of the enzyme complex (Helix pomatia), drizilase (Irpex lacteus) and chitinase (Streptomyces griseus) for 18 hours. The electron microscopic data on the two isogenic strains and their protoplasts are presented. The protoplasts proved to be a suitable initial material for investigating bioenergetic processes at the subcellular level and further genetic improvement of the strains. PMID- 1514858 TI - [Sensitivity of Vibrio and Aeromonas to antibiotics]. AB - The antibiotic sensitivity of 696 cultures belonging to the family Vibrionaceae (V. cholerae O1, V. cholerae non-O1, V. albensis, V. parahaemolyticus, V. alginolyticus and Aeromonas spp.) was studied and general regularities of the antibiotic sensitivity were shown: a high sensitivity to broad-spectrum antibiotics (tetracycline and chloramphenicol) and a low sensitivity to ++beta lactams (carbenicillin and ampicillin). The comparative examinations revealed similarity in the antibioticograms of V. cholerae O1 (el Tor++), V. cholerae non O1 and V. albensis, especially the latter two groups, as well as the tested halophilic Vibrio cultures by the range of the MICs, Mo, Me and the nature of the antibiotic resistance. Cultures of V. cholerae and luminescent Vibrio tended to preserve a high sensitivity. High resistance levels were noted in the halophilic Vibrio and Aeromonas cultures. No significant differences in the sensitivity of the strains of various origin (from man and environmental objects) were detected. However, several more resistant strains were isolated from the environmental objects. PMID- 1514859 TI - [Drug resistance of Mycobacterium tuberculosis]. AB - Drug resistance of Mycobacterium tuberculosis was followed up within a period of 1986 to 1989. There was a tendency to stabilization of resistance to streptomycin (42 per cent), tubazid (45.2 per cent) and ethionamide (up. to 1.4 per cent). Resistance to kanamycin slowly increased (by 3 to 6 per cent every year). Resistance to rifampicin markedly increased (almost 15 times). Resistance to ethambutol decreased (10 times). It was shown that the drug resistance could be lowered by using the drug combinations. PMID- 1514860 TI - [Antimicrobial and membranolytic activities of anti-burn drug fenozan]. AB - Fenozan, an anti-burn preparation, was shown to have antimicrobial activity against freshly isolated clinical strains of Staphylococcus aureus and Streptococcus faecalis, as well as against collection strains of the other gram positive bacteria. The antimicrobial action of the preparation was possibly due to impairment of permeability of the cytoplasmic membranes in the sensitive bacterial cells and their liberation of intracellular low molecular weight compounds to the environment. The membranolytic and minimum inhibitory concentrations of fenozan with respect to the sensitive bacterial cells were one order of magnitude lower than the concentration stabilizing the membranes of animal cells in the treatment of burns. Combination of the antioxidant and antimicrobial properties in fenozan was likely to provide its satisfactory therapeutic effect in the treatment of burn wounds. PMID- 1514861 TI - [Study of general toxic and organotropic properties of clindamycin in long-term experiments]. AB - The action of clindamycin monohydrate on the general state and weight rise, liver and kidney functions, peripheral blood count and pathomorphological state of the viscera was studied on rats in chronic experiments. Clindamycin was administered to laboratory animals orally in doses of 50, 100, 150 and 300 mg/kg. It was shown that some adverse reactions to the drug and in particular disorders in blood coagulation and morphological changes in the intestine did not depend on its dose and were due to duration of the drug use and probable development of dysbacteriosis. At the same time the disorders in the liver and kidney functions though transitory did depend, to a greater extent, on the dose and were evident after the antibiotic overdosage. PMID- 1514862 TI - [Eremomycin in the treatment of antibiotic-associated colitis in golden hamsters]. AB - The efficacy of eremomycin, a new glycopeptide antibiotic, was studied on a model of antibiotic-associated colitis in golden hamsters. The colitis was induced by intraperitoneal or intragastric administration of lincomycin. In a dose of 100 mg/kg administered orally once a day for 5 days eremomycin protected the animals from the lincomycin-induced colitis: some animals survived, the others died in later periods. When the animals were infected with a pathogenetic strain of Clostridium difficile followed by exposure to lincomycin the use of eremomycin produced the similar effect. PMID- 1514863 TI - [Effect of rifampicin and doxycycline on leukocyte chemotaxis]. AB - It was shown experimentally that in a dose corresponding to the average therapeutic one for man rifampicin was able to stimulate in vivo directed migration of neutrophils to the inflammation foci in mice CBA. Doxycycline used in a dose corresponding to the average therapeutic one was able to activate neutrophils and to increase chemotaxis. Intraperitoneal administration of doxycycline to guinea pigs induced liberation of large counts of neutrophils with marked segmentation of the nuclei to the peritoneal cavity. The cells induced by doxycycline had a higher capacity for chemotaxis under agarose as compared to the control. PMID- 1514864 TI - [Study of embryotoxic and teratogenic effects of amphotericin B and a methyl derivative of amphotericin B in rats after their intravenous and intra-amniotic administration]. AB - The embryotoxic action of amphotericin B and its methyl derivative was compared in rats after their intravenous and intraamniotic administration. The concentrations of amphotericin B and its methyl derivative in the amniotic cavity on days 13, 14 and 15 of pregnancy were 1.5 and 36 micrograms/ml, respectively. When administered intravenously during the preimplantation period the antibiotics had no embryotoxic action. Intravenous administration of amphotericin B in a dose of 500 micrograms/kg and its derivative in a dose of 2000 micrograms/kg during organ genesis induced a decrease in the craniocaudal size. In a dose of 3000 micrograms/kg administered intravenously the methyl derivative of amphotericin B induced an increase in postimplantation death rates. Administration of amphotericin B to the amniotic cavity had no damaging action. Administration of the methyl derivative on day 15 of pregnancy led to anomalous development of the lower extremities and slower ossification. The threshold doses by the embryotoxic action for intravenous administration are 500 micrograms/kg for amphotericin B and 2000 micrograms/kg for the methyl derivative. Administration of the antibiotics to the amniotic cavity revealed potential teratogenic properties of the amphotericin B methyl derivative. PMID- 1514865 TI - [Effects of interferon preparations on the course of Salmonella infection (experimental and clinical studies)]. AB - The effect of type I interferons on the process of experimental salmonellosis in mice and rabbits, as well as their effect on salmonellosis in patients was studied. It was shown that homologous interferon increased the animal survival rate, activated bactericidal activity of the phagocytic cells and increased elimination of the infectious agents from the host. The complex of the etiotropic and pathogenetic treatment of 32 patients with salmonellosis included human leukocytic interferon, leukinferon. It was administered intramuscularly in a dose of 1 x 10(4)-2 x 10(4) IU: three injections at intervals of 48 to 72 hours (the treatment course). The course was repeated 10 days after the last injection of the first course. Addition of leukinferon to the routine scheme of the medicinal treatment of salmonellosis provided recovery of all the patients without complications or appearance of the bacteria carriers (the observation period of more than 3 years). PMID- 1514866 TI - [Extracorporeal immunosuppressive effect of papain]. AB - Exposure of allogenic erythrocytes to papain induced their immunosuppressing properties within relatively narrow ranges of the incubation medium temperature (42 but not 37 or 40 degrees C) and the papain concentration (10 but not 2 or 50 micrograms/ml). Markedly pronounced immunosuppressing properties were acquired by the erythrocyte light fraction after heating and exposure to papain. The supernatant layer of adhesive spleen cells incubated in the presence of erythrocytes heat treated and exposed to papain suppressed development of the humoral immune response and DTH during the allogenic transfer and accelerated and increased excretion of the antigen specific immunosuppressing factor by the nonadhesive spleen cells of hyperimmunized sheep red blood cells. PMID- 1514867 TI - [Syndrome of excessive colonization of the small intestine]. PMID- 1514868 TI - [Methods of nucleic acid hybridization: their use in the detection and study of the prevalence of drug resistance genes]. PMID- 1514869 TI - [Isolation of nisin from native solution and its purification on cationites]. AB - It was found possible to use organic sorbents and in particular carboxylic cationites for isolation of nisin from the fermentation broth filtrate and its purification. Nisin is known as a polypeptide antibiotic applied as a preservative. The sorbents were shown to have high exchange capacities by the isolated substance and mechanical strength and resistance. They also proved to be highly stable. PMID- 1514870 TI - [Symposium "Ciflozin (ciprofloxacin)--a broad-spectrum antibacterial drug"]. PMID- 1514871 TI - [A rapid method of evaluation of the effectiveness of antibacterial drugs]. AB - Efficacy of antibiotics in the treatment of experimental tularemia was studied comparatively on various biological models. It was shown that the antibiotics which proved active against the tularemia microbe in albino mice when studied by the rapid and routine methods were highly efficient in the treatment and prevention of experimental tularemia in rabbits and baboons (hamadryas). The experiments showed basic possibilities to perform rapid estimation (for at least 2 days) of drug efficacy in experimental glanders and melioidosis in golden hamsters. The rapid method developed by the authors was recommended for the use in primary estimation of the efficacy of new drugs in the treatment of tularemia, glanders and melioidosis. PMID- 1514872 TI - Caudate glucose metabolic rate changes with both drug and behavior therapy for obsessive-compulsive disorder. AB - We used positron emission tomography to investigate local cerebral metabolic rates for glucose (LCMRG1c) in patients with obsessive-compulsive disorder before and after treatment with either fluoxetine hydrochloride or behavior therapy. After treatment, LCMRG1c in the head of the right caudate nucleus, divided by that in the ipsilateral hemisphere (Cd/hem), was decreased significantly compared with pretreatment values in responders to both drug and behavior therapy. These decreases in responders were also significantly greater than right Cd/hem changes in nonresponders and normal controls, in both of whom values did not change from baseline. Percentage change in obsessive-compulsive disorder symptom ratings correlated significantly with the percent of right Cd/hem change with drug therapy and there was a trend to significance for this same correlation with behavior therapy. By lumping all responders to either treatment, right orbital cortex/hem was significantly correlated with ipsilateral Cd/hem and thalamus/hem before treatment but not after, and the differences before and after treatment were significant. A similar pattern was noted in the left hemisphere. A brain circuit involving these brain regions may mediate obsessive-compulsive disorder symptoms. PMID- 1514873 TI - Cerebral glucose metabolism in childhood-onset obsessive-compulsive disorder. Revisualization during pharmacotherapy. AB - To investigate the effects of drug treatment in childhood-onset obsessive compulsive disorder (OCD), we repeated positron emission tomographic scans in 13 adults with OCD (eight taking clomipramine, two taking fluoxetine, and three taking no drug) after at least 1 year of pharmacotherapy. As a group, the patients had a significant improvement on all OCD and anxiety ratings. Positron emission tomography revealed a significant decrease in normalized orbitofrontal regional cerebral glucose metabolism (relative to global metabolism) bilaterally. Among the treated patients, the decrease in right orbitofrontal metabolism was directly correlated with two measures of OCD improvement. These results extend previous positron emission tomographic findings of regional dysfunction in OCD and suggest involvement of the orbitofrontal regions in the pathophysiology of OCD. PMID- 1514874 TI - Regional xenon 133 cerebral blood flow and cerebral technetium 99m HMPAO uptake in unmedicated patients with obsessive-compulsive disorder and matched normal control subjects. Determination by high-resolution single-photon emission computed tomography. AB - We measured regional cerebral blood flow (rCBF) with the xenon 133 (133Xe) inhalation method and with regional cerebral uptake of technetium 99m d,l hexamethyl propyleneamine oxime (99mTc-HMPAO) by single-photon emission computed tomography in 10 adult male patients with obsessive-compulsive disorder (OCD) and in 10 age-matched adult male normal controls. With the 133Xe method, there were no significant differences in cortical or basal ganglia blood flow between the patients with OCD and their matched controls. In the patients, there was a positive relationship between rCBF and the severity of both obsessive and compulsive symptoms (average r = .48). These rCBF findings were consistent with those of earlier reports of increased rCBF in patients with OCD who were undergoing imaginal flooding and who had exacerbation of symptoms following m-CPP administration. 99mTc-HMPAO is a lipophilic molecule that crosses the blood-brain barrier and is converted to a hydrophilic form that is trapped in the brain. The amount that is trapped is determined primarily by blood flow, but also by membrane permeability and kinetics of conversion of the 99mTc-HMPAO to the hydrophilic form. Compared with their matched controls, the patients with OCD had significantly increased 99mTc-HMPAO uptake in the high dorsal parietal cortex bilaterally, in the left posterofrontal cortex, and in the orbital frontal cortex bilaterally. Possible explanations include (1) increased rCBF that was not detected with 133Xe, (2) increased permeability of the blood-brain barrier and/or cell membranes, and (3) increased conversion and trapping of the lipophilic, injected form of 99mTc-HMPAO in these regions.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1514875 TI - Risks of affective illness among first-degree relatives of bipolar I old-order Amish probands. AB - Data from bipolar I old-order Amish families suggest that the morbid risk of illness is not significantly different in this population when compared with estimates of risk from previous studies. The age-corrected rates of bipolar I, bipolar II, and major depressive disorder among first-degree relatives are 8.7, 3.7, and 11.6, respectively. Risk of illness is not significantly different among male and female relatives and among relatives of male and female probands. Consistent with other reports, the rate of illness is higher among relatives of probands with early-onset disease. In contrast with previous reports, there does not appear to be a cohort effect in this population. PMID- 1514876 TI - An intriguing association between ancestral mortality and male affective disorder. AB - We examine the relationship between ancestral age at death and affective disorder. A cohort of 204 socioeconomically favored men was selected for mental and physical health 50 years ago and followed up until age 69 +/- 1 (+/- SD) years in an interdisciplinary study. During follow-up, 49 of these men were identified at some point as being psychosocially impaired. Of these 49 men, 25 were identified as having probable affective disorder based on family history of affective illness, clinical signs, subjective symptoms, clinical diagnosis, and choice of pharmacological treatment. Objective signs and symptoms distinguished these 25 men from the remaining 24 men, whose adjustment over the 50 years was equally psychosocially impaired, but who were never noted to be significantly depressed. The mean age at death of the maternal grandfathers for the 25 depressed men was 60.4 years, significantly younger than the mean age at death of maternal grandfathers for either the total sample (70.1 years) or the 25 psychosocially impaired but not depressed men (68.8 years). The mean age at death of the depressed men's other five first-degree ancestors was not significantly different from the age at death of the ancestors of the rest of the sample. If depressed alcohol abusers were excluded, the mean age at death of maternal grandfathers of alcohol abusers did not differ from that of the controls' maternal grandfathers. The evidence for possible X-chromosome linkage in male psychobiological vulnerability to affective spectrum disorder is discussed. PMID- 1514877 TI - Major depression and generalized anxiety disorder. Same genes, (partly) different environments? AB - Bivariate twin analysis can determine the extent to which two disorders share common genetic, familial environmental, or individual-specific environmental risk factors. We applied this method to lifetime diagnoses of major depression and generalized anxiety disorder as assessed at personal interview in a population based sample of 1033 pairs of female same-sex twins. Three definitions of generalized anxiety disorder were used that varied in minimum duration (1 vs 6 months) and in the presence or absence of a diagnostic hierarchy. For all definitions of generalized anxiety disorder, the best-fitting twin model was the same. Familial environment played no role in the etiology of either condition. Genetic factors were important for both major depression and generalized anxiety disorder and were completely shared between the two disorders. A modest proportion of the nonfamilial environmental risk factors were shared between major depression and generalized anxiety disorder. Within the limits of our statistical power, our findings suggest that in women, the liability to major depression and generalized anxiety disorder is influenced by the same genetic factors, so that whether a vulnerable woman develops major depression or generalized anxiety disorder is a result of her environmental experiences. PMID- 1514878 TI - Further evidence for family-genetic risk factors in attention deficit hyperactivity disorder. Patterns of comorbidity in probands and relatives psychiatrically and pediatrically referred samples. AB - We examined 140 probands with attention deficit hyperactivity disorder, 120 normal controls, and their 822 first-degree relatives using "blind" raters and structured diagnostic interviews. Compared with controls, probands with attention deficit hyperactivity disorder were more likely to have conduct, mood, and anxiety disorders. Compared with relatives of controls, relatives of probands with attention deficit hyperactivity disorder had a higher risk for attention deficit hyperactivity disorder, antisocial disorders, major depressive disorder, substance dependence, and anxiety disorders. Patterns of comorbidity indicate that attention deficit hyperactivity disorder and major depressive disorders may share common familial vulnerabilities, that attention deficit hyperactivity disorder plus conduct disorder may be a distinct subtype, and that attention deficit hyperactivity disorder and anxiety disorders are transmitted independently in families. These results extend previous findings indicating family-genetic influences in attention deficit hyperactivity disorder by using both pediatrically and psychiatrically referred proband samples. The distributions of comorbid illnesses in families provide further validation for subgrouping probands with attention deficit hyperactivity disorder by comorbidity. PMID- 1514879 TI - Toward a neuroanatomy of obsessive-compulsive disorder. PMID- 1514880 TI - There is more than one way to collect data for linkage analysis. What a study of epilepsy can tell us about linkage strategy for psychiatric disease. AB - The most popular strategy for finding genes in psychiatric diseases has been to focus on large pedigrees with many affected members. While this strategy has sound advantages, it also has drawbacks that have seldom been addressed. The strategy of using smaller families also has its place in a linkage analysis. To illustrate the point, I discuss herein the successful search for a gene for another common complex disease, namely, idiopathic primary generalized epilepsy. There, investigators in the Los Angeles (Calif) Epilepsy Program used mostly nuclear families who were chosen through a proband with highly specific characteristics. An independent study, using a different strategy but one still focused on small families, then confirmed the linkage. However, investigators of both epilepsy projects put much care into determining which clinical characteristics would be used to define the index cases. The implications for the study of psychiatric disease are as follows: (1) careful attention must be paid to clinical presentation, and (2) there is room for both large-pedigree and small family strategies in designing linkage studies. PMID- 1514881 TI - Zacopride in schizophrenia: a single-blind serotonin type 3 antagonist trial. PMID- 1514882 TI - Fluoxetine inhibits desipramine metabolism. PMID- 1514883 TI - Recovery following complete paraplegia. AB - Motor and sensory recovery were quantified by serial examinations prospectively performed on 148 persons with paraplegia. Of the 142 patients who remained complete injuries at follow-up, none with an initial neurologic level of injury (NLI) above T9 regained any lower extremity motor function at follow-up. Thirty eight percent of patients with an initial NLI at or below T9 had some return of lower extremity motor function, primarily in the hip flexors and knee initial NLI at or below T9 had some return of lower extremity motor function, primarily in the hip flexors and knee extensors. Twenty percent of the patients with an initial NLI at or below T12 regained sufficient hip flexor and knee extensor strength to reciprocally ambulate using conventional orthoses and crutches. Unlike motor function, recovery of light touch and sharp-dull discrimination was independent of the initial NLI. Six (4%) of the 148 patients demonstrated "late" conversion (more than 4 months after injury) from complete to incomplete spinal cord injury (SCI) status. Two of the 6 patients with an initial NLI at T12 and subsequent annual NLI at L1 and L2 reciprocally ambulated, and three of the 6 patients regained voluntary bladder/bowel control. PMID- 1514884 TI - Extensor carpi radialis recovery predicted by qualitative SEP and clinical examination in quadriplegia. AB - This prospective study examined the efficacy of the qualitative somatosensory evoked potential (SEP) and the initial clinical neurologic evaluation to predict motor power recovery of the extensor carpi radialis muscle (ECR). Twenty three C5 6 Frankel A-D spinal cord injured (SCI) subjects had SEPs of the median nerve (MN) and superficial radial nerve (SRN) performed within 72 hours to one week post injury. The MN and SRN cortical SEPs were qualitatively graded as either present or absent. Fifteen subjects whose initial ECR muscle strength was less than or equal to 3/5 and eight subjects whose muscle strength was greater than 3/5 were followed up to 12 to 18 months post injury for improvement in ECR muscle strength. The subject's ECR strength was evaluated by manual muscle testing (MMT) at 72 hours, weekly for three weeks, monthly for three months, and then at six, 12, and 18 months. The pin sensation at the C-5 dermatome was also tested at the above intervals and graded as either present or absent. A one tail Fisher Exact test compared the presence or absence of the MN and SRN SEPs to the recovery of the ECR to 3/5. The same one tail test also compared the presence or absence of the 72 hour C-5 pin sensation and the 72 hour MMT to the ECR recovery. Among the 15 subjects with an initial MMT of less than or equal to 3/5, ten subjects had successful ECR recovery (greater than 3/5); 5 did not. The C-5 pin sensation correctly predicted ECR recovery in all subjects studied (p less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1514885 TI - Intrathecal baclofen in hereditary spastic paraparesis. AB - Intrathecal baclofen has not been previously evaluated for the treatment of the disabling hypertonia associated with hereditary spastic paraparesis. Muscle tone and deep-tendon reflexes were evaluated in three patients with hereditary spastic paraparesis after a double-blind, cross-over bolus injection of intrathecal baclofen. Patients underwent placement of a subcutaneous pump for continuous infusion of intrathecal baclofen. Three months after implantation the muscle tone decreased 2.04 points (p less than .0001) and the reflex score decreased 2.25 points (p less than .001). Patients initially reported subjective weakness, but muscle testing revealed either an increase or no change in voluntary motor function. Baclofen doses of 60 to 264 micrograms per day were required for effective control of muscle tone and spasticity. Much of the disability in familial spastic paraparesis may be related to the loss of suprasegmental inhibition of spinal reflexes overwhelming the residual voluntary motor function. PMID- 1514887 TI - Pressure ulcer, fibronectin, and related proteins in spinal cord injured patients. AB - Pressure ulcer is a common occurrence in spinal cord injured (SCI) patients and can lead to serious complications. With proper management, some patients exhibit satisfactory healing whereas others show slow or nonhealing ulcers. Fibronectin has been shown to accumulate in wound, opsonize macroaggregate debris for phagocytosis, promote revascularization, and facilitate fibroblast migration and proliferation. We explored the relationship of plasma fibronectin with healing potential in 21 SCI men with pressure ulcer. They received standard wound care and were observed for eight weeks. Ten otherwise healthy SCI men without pressure ulcer (SCI-controls) and 32 able-bodied normal individuals (normal controls) were also studied. Plasma fibronectin and related proteins, ie, fibrinogen, plasminogen, alpha 2-antiplasmin and Factor XIII, were measured. Ten of 21 SCI patients with pressure ulcer showed rapid healing within four weeks and had significantly higher fibronectin levels as compared with the 11 patients with poor healing ulcers, SCI controls, and normal controls. Factor XIII and alpha 2 antiplasmin were mildly reduced and fibrinogen values were significantly increased in all SCI groups. Plasminogen concentrations were comparable in all groups studied. It thus appears that plasma fibronectin rises in patients with fast healing ulcers but fails to do so in those with poor healing ulcers and as such may be predictive of the course of pressure ulcers. PMID- 1514886 TI - Clean and sterile intermittent catheterization methods in hospitalized patients with spinal cord injury. AB - The purpose of this study was to compare the incidence of urinary infection using clean intermittent catheterization with the incidence of infection using sterile intermittent catheterization in patients hospitalized with spinal cord injury who were not receiving prophylactic antibiotics. Forty-six patients were assigned randomly to a clean (n = 23) or sterile (n = 23) study group. Catheterizations were done at least every six hours. Infection was defined as bacteriuria greater than or equal to 100,000 organisms/mL or greater than or equal to 10,000 organisms per mL with fever of 100 degrees F or greater. Results of urinary dipslides were recorded daily. Twenty-eight subjects (60.9%) converted to greater than or equal to 100,000 organisms per mL. Method of catheterization was neither associated significantly with development of greater than or equal to 100,000 organisms per mL. (X2[1,46] = .36, p = .55) nor with symptomatic infections (X2[1,46] = .15, p = .70). Data support the use of clean intermittent catheterization under the conditions used in this study, including the use of a sterile catheter each day and careful monitoring of infection and technique. Before using this method with other diagnostic groups or in different clinical settings, further investigation is needed. PMID- 1514888 TI - Contractures in neuromuscular disease. AB - The percentage of subjects with contractures, mean maximal loss of range, and relative contracture indices are reported in 230 patients, with 11 diseases seen in a neuromuscular disease clinic during a five-year period. The highest percentage of contractures occurred in patients with Duchenne muscular dystrophy. The number of contractures was significantly greater (p less than .001) (1) in the lower than in the upper extremities; (2) in diseases considered myopathic than in those considered neuropathic; (3) in diseases that are X-linked than in those that are not; and (4) in rapidly progressive than in slowly progressive diseases. PMID- 1514890 TI - Muscle and bone pressure pain threshold and pain tolerance in fibromyalgia patients and controls. AB - Pressure pain thresholds and pressure pain tolerances on non-trigger-point muscle and bone were measured with a dolorimeter in 46 female patients with primary fibromyalgia and in 50 healthy women of the same age. The pressure pain thresholds and the pressure pain tolerances on both muscle and bone were lower in the fibromyalgia patients than in the healthy controls. All the differences were statistically highly significant, though there was a certain degree of overlapping between the patients and the controls. It is concluded that patients with primary fibromyalgia have a generalized amplification of pain sensitivity, a sign that might be useful in the diagnosis of fibromyalgia. PMID- 1514889 TI - Lower extremity amputation in scleroderma. AB - Scleroderma or Systemic Sclerosis (SSC) is a disorder characterized by fibrosis of the skin and multiple internal organs. The pathological lesion is a triad of small artery intimal proliferation, medial thinning and adventitial scarring. Autoamputation of fingers and toes is often seen, but only a few cases of limb amputation in scleroderma patients have been reported. The Pittsburgh Scleroderma databank includes 1,030 patients with SSC. Among these were seven patients who sustained lower limb amputation. There were four patients with the CREST variant of SSC, two with diffuse scleroderma, and one who had SSC/rheumatoid arthritis/polymyositis overlap who sustained limb amputation. Of the seven, three were male and five had a significant smoking history. Ages ranged from 46 to 71 years. All patients underwent amputation for nonhealing ulcerations. No problems with postoperative wound healing were seen. Pathologic changes typical of SSC in addition to atherosclerotic peripheral vascular disease were described in one case. Three patients were successfully fitted with prostheses and became independent ambulators. Four patients could not be fitted with prostheses. No skin problems were reported related to prosthetic use. Our review demonstrates that SSC patients who undergo amputation can become successful prosthetic users and should be considered for prosthetic prescription. PMID- 1514891 TI - Thermographic imaging of myofascial trigger points: a follow-up study. AB - Thermographic evaluation was performed on 11 adult volunteers with myofascial trigger points and on 11 asymptomatic controls. Infrared thermography was used to obtain a series of images to compare the sensory referral areas of myofascial trigger points with their thermal referral patterns. A series of images was then taken at, and distal to, the sensory referral area of each trigger point during quantitative compression of the trigger point, and dynamic temperature changes were monitored. Asymmetric thermal patterns were observed at all trigger points in the sensory referral area and distal to the referred area before compression. The thermal referral areas showed a reduction in temperature from precompression levels during compression. When similar but asymptomatic areas were compressed, no significant changes in temperature were noted at distal sites. PMID- 1514892 TI - Correlation analysis of somatosensory evoked potential waveforms. AB - Somatosensory evoked potential (SEP) waveforms were recorded over the spine and scalp in response to tibial nerve stimulation at the ankle for 28 subjects. The scalp data were analyzed with the correlation coefficient (CC) to determine the reproducibility of the signals and to identify side-to-side symmetry. The test for reproducibility uses the CC to verify validity, a low CC implying that the data are defective. The symmetry test uses the CC to obtain a measure of similarity of the responses to stimulation from opposite sides of the body. Statistics are presented showing the normal ranges of the CC values and their standard deviations. We conclude that the CC can provide objective and quantitative waveform information that complements latency and amplitude measurements in the clinical interpretation of tibial SEP waveforms. PMID- 1514893 TI - Computer algorithms to characterize individual subject EMG profiles during gait. AB - Three methods of precisely determining onset and cessation times of gait EMG were investigated. Subjects were 24 normal adults and 32 individuals with gait pathologies. Soleus muscle EMG during free speed level walking was obtained with fine wires, and was normalized by manual muscle test (%MMT). Linear envelopes were generated from the rectified, integrated EMG at each percent gait cycle (%GC) of each stride in individual gait trials. Three methods were used to generate EMG profiles for each tested subject. The ensemble average (EAV) was determined for each subject from the mean relative intensity of the linear envelopes. Low relative intensity or short duration EMG was removed from the ensemble average to create the intensity filtered average (IFA). The packet analysis method (PAC) created an EMG profile from the linear envelopes in successive strides whose respective centroid %GC locations were within +/- 15%GC of each other. Control values for onset and cessation times of individual gait trials were calculated after spurious outliers were removed. Mean onset and cessation times across subjects for control values and the experimental methods (EAV, IFA, and PAC) were calculated. Dunnett's test (p less than .05) was performed to compare control and experimental groups in patient and normal trials. EAV differed from control values for onsets (p less than .01), cessations (p less than .01), and durations (p less than .01) in both normal and patient trials. IFA and PAC had no significant differences from control value means. IFA was selected for clinical use as automatic analysis could be performed on all trials and a minimum number of decision rules were needed. PMID- 1514894 TI - Ulnar palmar cutaneous nerve and hypothenar sensory conduction studies. AB - The ulnar palmar cutaneous nerve (UPCN) is potentially useful to the electrodiagnostician. However, no definitive nerve conduction study techniques for the UPCN have been reported. The UPCN supplies sensory innervation to the hypothenar palm. This study describes an orthodromic sensory conduction technique for the hypothenar palm. Data were collected from 20 normal limbed patients (ages 22-58). Potentials were recorded over the ulnar nerve 10cm proximally and at the elbow. Distal latency was 2.19 +/- 0.17msec, and distal amplitude was 12.7 +/- 6.9uv. Additionally, a modified collision technique was used in several subjects to examine the possibility of volume conduction to more than one ulnar nerve branch. The techniques described may be useful in selected cases of distal ulnar nerve pathology. A case is reported in which injury to the superficial sensory branch of the ulnar nerve, with sparing of the UPCN was demonstrated electrodiagnostically. Further study is needed to determine if the UPCN can consistently be electrophysiologically isolated. PMID- 1514895 TI - Functional screening of lower-limb amputees: a role in predicting rehabilitation outcome? AB - The Functional Independence Measure (FIM), a single-score instrument used to measure independent functioning in six areas of basic self-care skills, was used to evaluate 68 patients following lower-limb amputation. Patients in a rehabilitation hospital were assessed with the FIM upon admission and discharge. Admission scores averaged 52.7, ranging from 25.2 to 70.0. Patients scoring in the lowest and highest quartiles were compared: no remarkable gender, ethnic, or age differences were evident. Persons with the lowest scores (ie, lowest functioning) had a higher prevalence of hypertension, coronary artery disease, and noninsulin-dependent diabetes mellitus. The success of rehabilitation in patients in the lower two quartiles upon admission was variable and not predicted well by the FIM. In contrast, predictability of rehabilitation success was high in patients functioning higher at admission, the majority achieving near-perfect scores by discharge. Length of hospitalization appeared to be largely unrelated to the net difference in FIM scores over the course of hospitalization. PMID- 1514896 TI - Functional recovery in young stroke patients. AB - Thirty young stroke patients were retrospectively assessed for levels of activities of daily living and of basic functional movements. Scores upon admission, discharge, and follow-up were compared in order to evaluate course of rehabilitation and functional outcome. Mean length of stay in the rehabilitation ward was 87 +/- 17 days, and duration of follow-up was 31 +/- 8 months. Multivariate analysis of covariance confirmed significant improvements during hospitalization, in transfer, standing, sitting and walking abilities (F = 3.5, p less than 0.02), as well as in activities of daily living (F = 4.7, p less than 0.01). Further improvement during the follow-up period was observed for standing and walking abilities (F = 10.2, p less than 0.001) only. No fatalities occurred among the patients during the study period. Eighty-one percent of the patients resumed their previous or other jobs six months after discharge. We conclude that for young stroke patients admitted to a rehabilitation ward shortly after the event, prognosis in terms of survival and functional outcome is favorable, and independent of precipitating factor, age, sex, or side of weakness. PMID- 1514897 TI - Clonidine transdermal system for treatment of spasticity in spinal cord injury. AB - Clonidine tablets have been used in the past for treatment of spasticity with some success. The use of clonidine, however, has been limited by adverse effects, mainly hypotension. Over a two-year period, 17 patients were started on clonidine transdermal delivery system. They were followed for up to 18 months. Twelve of the 17 patients had a beneficial response and have continued on the patch. In ten of these 12 patients, other antispasticity drugs were either reduced or discontinued. In another three of the 17 patients, the response was good, but the patch was discontinued. No patient demonstrated persistent problematic hypotension. Clonidine Transdermal Patch appears to be an effective treatment for spasticity after a spinal cord injury. Adverse effects appear to be minimized using this mode of delivery. PMID- 1514898 TI - Galactorrhea: a complication of spinal cord injury. AB - Galactorrhea, a secretion of milk or milk-like products from the breast in the absence of parturition, has been reported to occur in women with spinal cord injuries in association with amenorrhea and hyperprolactinemia. Four cases of galactorrhea in association with spinal cord injury are reported. Galactorrhea developed in four spinal cord injured women who had thoracic paraplegia. The onset of galactorrhea was from one month to five months after injury. Although the onset of galactorrhea may have been related to prescribed medications in all four cases, insufficient data exist to draw conclusions. The three women whose galactorrhea persisted declined treatment and galactorrhea continuing for more than two years in one instance. We conclude that galactorrhea with or without amenorrhea may develop after a spinal cord injury and that spinal cord injured women may have an enhanced sensitivity to medication-induced galactorrhea. PMID- 1514899 TI - Avulsion fracture of the anterior superior iliac spine in a collegiate distance runner. AB - Overuse injuries are a common occurrence with distance runners, yet injuries to the iliac crest are rare in this population. When an iliac crest injury occurs, it is usually associated with the weak unossified growth plate. The condition may present itself as apophysitis and may progress to an avulsion fracture. This is a report of a rare case in which a collegiate distance runner had an avulsion fracture of his anterior superior iliac spine (ASIS). Treatment consisted of rest followed by nonweight-bearing graded exercise performed in the pool and on a Schwinn Airdyne. The graded exercise not only strengthened and stabilized the muscles acting on the hip and thigh, but it also enabled the athlete to maintain his cardiorespiratory endurance. He returned to competition three weeks after the injury. PMID- 1514900 TI - Isokinetic exercise system modification for short below-the-knee residual limbs. AB - The use of isokinetic exercise has been shown to be an effective way of strengthening debilitated muscles. In the below the knee amputee, significant quadriceps and hamstring muscle wasting has been documented. Although isokinetic strengthening of the debilitated knee extensors and flexors in the below the knee amputee would be beneficial, there are no fully described isokinetic equipment modifications in literature that would allow a short below the knee amputee to effectively use isokinetic equipment. This article describes such a modification. PMID- 1514901 TI - The puzzle people: memoirs of a transplant surgeon. PMID- 1514902 TI - Icons in surgery. AB - This company of surgeons, the Pacific Coast Surgical Association, has honored me greatly, and I am grateful. In a turbulent, changing world, as physicians, you are among the most important people on earth. More important, by far, than any technologic aspect of your craft, is your character. As the pen is mightier than the sword, your beliefs and values are the sustaining force that will guide you in troubled times. Icons are Everyman's "pointers of the way" in meeting the challenges of tomorrow. PMID- 1514903 TI - 63rd annual meeting of the Pacific Coast Surgical Association. Kauai, Hawaii, February 16-19, 1992. PMID- 1514904 TI - Long-term efficacy of octreotide in the treatment of Zollinger-Ellison syndrome. AB - Nine patients with Zollinger-Ellison syndrome were treated with octreotide acetate (100 micrograms delivered subcutaneously three times daily) and followed up for 1 to 48 months. Serum gastrin levels were obtained at predetermined intervals. All patients had elevated baseline fasting gastrin levels (greater than 150 ng/L [greater than 150 pg/mL]). One month after administration of octreotide, gastrin levels were in the reference range for five (62%) of eight patients, and a mean gastrin suppression rate of 76% was achieved (ie, values were a mean of 76% less than baseline values). One year after administration of octreotide, five (71%) of seven evaluable patients had gastrin levels of less than 200 ng/L (200 pg/mL), and the mean gastrin suppression rate was more than 80% for these seven patients. During the second year, control at these levels was maintained in four patients; one patient continued to have controlled levels for 42 months. Complete symptomatic response occurred in seven patients (78%), and partial response in two patients (22%). All six patients with diarrhea before treatment were cured of it. Octreotide acetate provides efficacious long-term suppression of elevated gastrin levels and excellent symptomatic relief in patients with Zollinger-Ellison syndrome. PMID- 1514905 TI - Breast conservation management of breast tumors 4 cm or larger. AB - Randomized studies of stage I and II breast cancer have shown that breast conservation treatment is equivalent to modified radical mastectomy in regard to local-regional control and survival. Little has been published on breast conservation for patients with large tumors. We analyzed 68 patients with tumors measuring 4 cm or larger (range, 4 to 12 cm) treated with breast-conserving surgery and radiation therapy. The median follow-up was 46 months; the mean tumor size was 5 cm. The 5-year actuarial local-regional recurrence rate was 8.5%, and the overall survival and disease-free survival rates were 76% and 68%, respectively. We conclude that breast conservation treatment may be a reasonable alternative to mastectomy in patients with tumors 4 cm or larger without compromise in local-regional control or survival, while achieving acceptable cosmesis. PMID- 1514906 TI - Long-segment Hirschsprung's disease. AB - We identified 21 children (14 boys and seven girls) with long-segment Hirschsprung's disease defined as aganglionosis extending proximal to the ileocecal valve. Long-segment Hirschsprung's disease is difficult to diagnose and treat; symptoms may be mild, and diagnosis delayed. Abdominal distention and constipation or delayed passage of meconium are the most common symptoms. Radiologic studies are unreliable in establishing the diagnosis. The morbidity rate is high because of the high transition zone and short gut. The long-term outcome of patients after the standard Duhamel procedure is satisfactory, except with extremely high transition zones. Pull-through procedures should not be performed in the small infant, but should be delayed until patients are old enough to be continent. PMID- 1514907 TI - Examination of the patient with a knee dislocation. The case for selective arteriography. AB - One hundred fifteen patients with a unilateral knee dislocation underwent arteriography to examine the popliteal artery. The incidence of popliteal artery injury was 23% (27 patients). Clinically, 29 (25%) of the 115 patients had an abnormal ipsilateral pedal pulse and 23 (79%) of these 29 patients had an arteriographically identified popliteal artery injury. Twenty-two arteries were surgically repaired and one was treated without surgery. Eight-six patients had normal pulses; the arteriogram showed no abnormalities in 77, demonstrated spasm in five, and revealed an intimal flap in four. All 86 patients were treated without surgery and had no delayed vascular complications. This demonstrates that the vascular examination is an accurate predictor of major popliteal artery injury following knee dislocation. Patients with an abnormal pedal pulse warrant arteriography due to a high incidence (79%) of popliteal artery injury. Patients with normal pulses may be monitored by clinical examination only. Popliteal artery injuries in this group are minor and rarely require intervention. PMID- 1514908 TI - Surgical treatment and chemotherapy for pulmonary metastases from osteosarcoma. AB - Between 1971 and 1991, 247 patients with stage I osteosarcoma were treated at UCLA. Patients were treated in four sequential groups, with group 1 receiving surgery alone, and groups 2 through 4 receiving various adjuvant chemotherapeutic regimens. The incidence of lung metastases in these patients decreased from 92% (group 1) to 31% (group 4), while the proportion of patients undergoing pulmonary resection increased (17% vs 82%). Overall 5-year survival rate among patients with pulmonary metastases increased from 0 in group 1 to 41% (actuarial) in group 4. No clinical factor correlated significantly with outcome using univariate analysis, although there was a trend toward prolonged survival in those with longer disease-free intervals. Adjuvant chemotherapy and resection of pulmonary metastases have transformed a uniformly fatal condition into one with a reasonable expectation of long-term survival. PMID- 1514909 TI - Neonatal cardiac transplantation. Intermediate-term results and incidence of rejection. Loma Linda University Pediatric Heart Transplant Group. AB - Early age at cardiac transplantation may favor successful engrafting with minimal chronic immunosuppression. Fifty-two newborns underwent orthotopic heart transplantation; 47 (90%) survived the operation, and 44 (85%) were late survivors. Actuarial survival was 92% at 1 month, 86% at 1 year, and 84% at 5 years. Forty-four infants who survived 12 weeks and the corresponding 100 rejection episodes were analyzed. Mean follow-up was 2.2 years. The mean number of rejections per year of follow-up was 1.2. No episodes of rejection were identified in six patients. Seven patients had a late rejection episode more than 1 year after transplantation, and only one had a late rejection episode after 2 years. Neonatal cardiac transplantation is effective and durable therapy for uncorrectable heart disease. Intermediate-term results are excellent. Severe rejection is uncommon, and few episodes occur after 1 year of follow-up. PMID- 1514910 TI - Management of bile duct strictures. An evolving strategy. AB - In an effort to determine the role of interventional radiologic and endoscopic techniques in the management of benign biliary strictures, a retrospective analysis was carried out on 194 consecutive patients with bile duct strictures treated at UCLA between 1955 and 1990. Patients were classified as group 1 (1955 through 1979; n = 138) or group 2 (1980 through 1989; n = 56). Follow-up was for a minimum of 24 months and was in excess of 3 years in 179 patients (92%). Although the incidence of recurrent strictures was similar in the two groups (21% and 23%), the reoperation rate was significantly lower (P less than .02) in group 2 (6%) than in group 1 (21%). Percutaneous transhepatic biliary dilatation, used in 20 patients in group 2, was successful in 13 (93%) of 14 patients with anastomotic strictures and three (50%) of six patients with primary strictures (P less than .05). We conclude that surgical reconstruction remains the standard therapy for patients with primary bile duct strictures. Percutaneous transhepatic biliary dilatation has limited usefulness for these patients, but may be more appropriate for those with anastomotic strictures. PMID- 1514911 TI - Care for victims of urban violence and the education of trauma and critical care surgeons. A troubled partnership? AB - This article reviews the current status of trauma care education and its relationship to critical care education. The critical linkage of both of these endeavors with urban hospitals oriented to indigent care is stressed. Within the specialty of surgery, the recent progress toward resolution of conflicts that have threatened trauma and critical care education programs is reviewed. The partnership between the trauma programs of urban hospitals will be strengthened by this resolution. PMID- 1514912 TI - The MEE/PEE ratio as a predictor of excess weight loss for up to 1 year after vertical banded gastroplasty. AB - Thirteen morbidly obese individuals were studied prospectively for 1 year after vertical banded gastroplasty (VBG) to determine the relationships between energy balance equation parameters and excess weight loss. The measured energy expenditure (MEE), as determined by indirect calorimetry, was not correlated with weight loss. However, when this parameter was expressed as a ratio to the predicted energy expenditure (PEE), the ratio was significantly correlated with the postoperative excess weight loss at 2, 6, and 12 months. The mean daily energy intake after the VBG was 2715 +/- 865 kJ. The postoperative energy intake was not correlated with the excess weight loss. Diet-induced thermogenesis was studied in eight patients. The mean diet-induced thermogenesis was 10.31% +/- 13.92%. The diet-induced thermogenesis was not correlated with the postoperative excess weight loss. The preliminary findings of this trial suggest that the MEE/PEE ratio is useful in predicting excess weight loss after VBG. PMID- 1514913 TI - Detection of occult tumor using indium 111-labeled anticarcinoembryonic antigen antibodies. AB - Even with the advancement of radiologic techniques, metastatic cancers can still be difficult to detect. In this study, 48 patients suspected of having occult metastases were studied by radioimmunodetection following the administration of 92.5 to 181.3 MBq of indium 111-labeled monoclonal anticarcinoembryonic antigen antibody. All but seven patients were thought to have metastatic colorectal carcinoma. In the majority of cases, physical examinations and computed tomographic scans had failed to detect a lesion. At least one lesion that was later proved to exist was detected in 34 of the 50 studies performed on these patients. Seven of eight patients with normal radioimmunodetection scans remain free of disease. One hundred one sites were detected overall; 60 were considered true-positive sites and 27 false-positive sites. Fourteen sites remained in question. Nineteen false-negative sites occurred. Radioimmunoimaging appears valuable for the detection of occult cancer where standard, noninterventional techniques have failed to detect the suspected disease. PMID- 1514914 TI - Bacterial translocation after major hepatectomy in patients and rats. AB - Bacterial infections are frequent complications after liver resection. Of 138 patients who underwent major hepatectomy, 11 patients (8%) developed intra abdominal sepsis in the postoperative period. Seven bacterial strains of gut origin were isolated from the abdominal cavity. Eight patients had multiple bacteria cultured. In the experimental studies on rat models, positive mesenteric lymph node cultures were seen 2 hours after removal of 70% and 90% of the total weight of the rat liver, and 12 hours after 50% hepatectomy, persisting for 3 and 4 days after 50% and 70% hepatectomy, respectively. The incidences of bacteremia 2 and 4 hours after 90% hepatectomy were 80% and 100%, respectively; 6 hours after 70% liver resection, the incidence of bacteremia was 33%. Blood cultures were positive in only 6% of the rats following 50% hepatectomy, and in none of the controls. Thus, bacterial translocation occurs in the early course after hepatectomy, the incidence being proportional to the amount of liver tissue removed. PMID- 1514915 TI - A decade of oral anticoagulant treatment to maintain autologous vein grafts for femoropopliteal atherosclerosis. AB - To determine whether long-term oral anticoagulant treatment was effective in improving graft performance and preventing major amputation following vein bypass surgery for femoropopliteal atherosclerosis, a clinical trial was conducted in one single center and continued during 10 years. After 130 patients had electively received a femoropopliteal vein graft, they were randomly assigned to a therapy group (treatment with phenprocoumon [n = 66]) or to a control group (n = 64) that remained without any anticoagulant treatment. Primary end points of the study were graft reocclusion and limb loss. The median durations of primary patency and limb salvage were significantly longer for treated patients than that for controls. In addition, survival in the therapy group was longer. Following autologous vein bypass surgery in the treated group, the results were superior in terms of graft patency, limb salvage, and survival. PMID- 1514916 TI - Familial chronic recurrent pancreatitis in identical twins. Case report and review of the literature. AB - Familial presentation of chronic recurrent pancreatitis in childhood is rare. The etiology of this illness is obscure, and its hereditary properties are not well defined. Simultaneous occurrence of chronic recurrent pancreatitis in identical twins with the same clinical presentation and similar typical pancreatographic abnormalities is exceptional. Twin sisters, aged 9 years, were admitted to the hospital because of recurrent attacks of pancreatitis. Ultrasound examination revealed an enlarged irregular pancreatic duct in both girls, and endoscopic retrograde cholangiopancreatography showed a distorted duct with multiple strictures and dilatations similar to a "chain of lakes" pattern. Both patients underwent longitudinal pancreatojejunostomy within a month. The therapeutic regimen and preoperative and surgical treatment of such patients are discussed, as is the optimal timing of intervention. PMID- 1514917 TI - Splenopneumopexy to treat portal hypertension produced by venous occlusive disease. AB - Splenopneumopexy is intended to induce collateral circulation between the portal system and the pulmonary veins. It involves performing a parenchymatous anastomosis between the amputated superior pole of the spleen and the exposed pulmonary venous structures in the left lower lobe. This operative procedure was used to treat four patients with extended portal-splenic-mesenteric venous occlusion who did not respond satisfactorily to sclerotherapy. The patients underwent transfemoral embolization of their splenic arteries before splenopneumopexy. Following the operations, all patients have remained well, experiencing cessation of gastrointestinal bleeding for up to 48 months. Splenopneumopexy may be a therapeutic alternative in selected patients with portal hypertension, including those patients with widespread occlusion of the portal vein and its radicles. PMID- 1514918 TI - Concerning the Letton-Q 'uncut' Roux limb. PMID- 1514919 TI - Roux stasis syndrome: treatment by pacing and prevention by use of an 'uncut' Roux limb. PMID- 1514920 TI - Binding characteristics of ortho-toluidine to rat hemoglobin and albumin. AB - The binding characteristics of [14C]ortho-toluidine (OT), a suspect human carcinogen, were investigated in male Sprague-Dawley rats. Rats were administered [14C]OT i.p. at 10, 20, 40, 50, or 100 mg/kg body weight, then sacrificed at 2, 4, 8, 18, 24, 48, or 72 h, or 7, 14, or 28 days. Hemoglobin (Hb) and albumin (Alb) were isolated from blood, and OT binding was determined by liquid scintillation counting. For Alb, peak binding occurred at 50 mg/kg at the 4-h time point (15.6 ng OT/mg Alb), while for Hb peak binding was observed at 24 h at the 100 mg/kg dose (23.0 +/- 5.1 ng OT/mg Hb). OT-Alb binding was not linear; however, OT-Hb binding appeared to increase linearly in a dose-dependent manner. Biological half-lives of OT bound to Alb or Hb were observed to be 2.6 and 12.3 days, respectively, after rats were administered a single dose of [14C]OT and sacrificed after 4 h to 28 days. The effect of route of administration on OT-Hb adduct formation was investigated, and approximately a two-fold increase in radioactivity bound to Hb was observed after i.p. administration of 100 mg/kg [14C]OT versus oral intubation. Additional studies were carried out to investigate the effect of microsomal enzyme induction. An increase in OT-Hb binding was seen in rats pretreated with phenobarbital compared to rats pretreated with beta-naphthoflavone or without pretreatment; however, this increase was not statistically significant. These results suggest that OT-Hb and OT-Alb adduct formation may be a valuable biomarker for assessing workplace exposure. PMID- 1514921 TI - Interlaboratory comparison of microsomal ethoxyresorufin and pentoxyresorufin O dealkylation determinations: standardization of assay conditions. AB - Assay conditions and results of cytochrome P-450 dependent 7-ethoxyresorufin (ER) and 7-pentoxyresorufin (PR) O-dealkylation (OD) by rat liver microsomes were compared by four laboratories in the Netherlands. Microsomal mixtures were prepared from control, 3-methylcholanthrene and phenobarbital pretreated animals, resulting in different levels of cytochrome P-450 isozymes. EROD and PROD activities were determined in each laboratory according to their own protocols. Considerable variability was found both between and within laboratories. Further studies demonstrated that protocol differences are important factors causing this interlaboratory variation. Main factors of influence were buffer type, batch of resorufin used for calibration, substrate solvent and substrate concentration. Based on the results obtained, standardized protocols for optimized measurement of microsomal EROD and PROD activities were developed. Additional experiments demonstrated that the use of these standardized protocols reduced intralaboratory variation in both the EROD and the PROD assay, whereas it also reduced the interlaboratory variability for the PROD determinations. The interlaboratory variation for measurement of microsomal EROD activities was only reduced for the laboratories using a Cobas-Bio analyzer. The results of the present study demonstrate clearly that data obtained with EROD and PROD activity measurements are highly sensitive to factors frequently varying from one laboratory to another. In addition, they demonstrate the necessity to be careful with absolute values presented in the literature for these activities, unless well characterized assay conditions are applied. PMID- 1514922 TI - Effect of 2,3,7,8-tetrachlorodibenzo-p-dioxin on benzo(a)pyrene hydroxylase activity in embryos of the Japanese medaka (Oryzias latipes). AB - When Japanese medaka embryos were exposed to 12 ng/l 2,3,7,8-tetrachlorodibenzo-p dioxin (TCDD) beginning on the day of fertilization (day 0), benzo(a)pyrene hydroxylase (B(a)PH) activity was induced in the whole embryo 105,000 g fraction by day 5 of development, which coincided with liver development. The induction of B(a)PH activity also coincided with the appearance of 2,3,7,8-TCDD induced hemorrhagic and edematous lesions. B(A)PH induction only occurred in embryos exposed to toxic concentrations (greater than 10 ng/l) of 2,3,7,8-TCDD. B(a)PH induction also occurred in embryos after exposure to 10 ng/l 2,3,7,8 tetrachlorodibenzofuran (TCDF) and 50 micrograms/l 1,2,7,8-TCDD. Both 2,3,7,8 TCDF and 1,2,7,8-TCDD are toxic to Japanese medaka embryos at concentrations that resulted in the induction of B(a)PH activity. B(a)PH activity was not induced by the non-toxic congener 1,3,6,8-TCDD at concentrations as high as 50 micrograms/l. The structure activity relationship for B(a)PH induction in Japanese medaka embryos was similar to that which is observed in other species and biological systems, suggesting that the biological activities of these compounds may also be mediated through the putative Ah receptor in these fish embryos. At 50 micrograms/l, beta-naphthoflavone (BNF) induced B(a)PH activity in Japanese medaka embryos to similar levels as 2,3,7,8-TCDD did at toxic concentrations. However, at 50 micrograms/l, BNF was not toxic to Japanese medaka embryos. Therefore, the induction of B(a)PH activity probably did not directly result in the toxicity observed in these fish embryos after exposure to 2,3,7,8-TCDD. PMID- 1514923 TI - Polyhalogenated dibenzo-p-dioxins and dibenzofurans and the immune system. 4. Effects of multiple-dose treatment with 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) on peripheral lymphocyte subpopulations of a non-human primate (Callithrix jacchus). AB - Non-human primates (Callithrix jacchus) were treated with 2,3,7,8 tetrachlorodibenzo-p-dioxin (TCDD) over a period of 30 weeks, and lymphocyte subpopulations of venous blood were monitored using monoclonal antibodies and flow cytometry (FACScan). There was no clear-cut change in the total lymphocyte population during this study. In the first part of the study the new-world monkeys (marmosets) were treated for 24 weeks with a weekly dose of 0.3 ng TCDD/kg body wt. At the end of this treatment period a level corresponding to an actual cumulative dose of about 2.5-2.7 ng TCDD/kg body wt was expected. The percentage and the absolute number of the CD4+CDw29+ cells ("helper inducer" or "memory" cells) surmounted the physiologically occurring increase. Concomitantly the percentage of the CD4+CD45RA+ cells ("suppressor-inducer" or "naive" cells) decreased. There was, at the same period, no change in the total T cell population (CD2+ cells) or in the cells carrying the CD8 or the CD4 epitope. When increasing the weekly dose to 1.5 ng TCDD/kg body wt, a transient increase in the percentage and the absolute number of the CD8+CD56+ cell population ("cytotoxic T cells") was observed 3 weeks after the increase in dosing. At this time the expected decrease in the percentage or the absolute number of CD4+CDw29+ cells was just detectable and this decline was at its maximum 6 weeks after switching to the higher weekly doses. The reduction in the percentage and the absolute number of CD4+CDw29+ cells persisted 5 weeks after discontinuation of the dosing, but this cell population was again within normal limits 7 weeks later. Because the two subpopulations are changed in opposite directions, the ratio CD4+CDw29+/CD4+CD45RA+ is a very sensitive measure of the effect induced by TCDD. There was a pronounced decrease in the percentage of the CD20+ cells (B1 cells), but their percentage and number rapidly normalized, in contrast to the CD4+CDw29+ cells, when the dosing was discontinued. At the end of the treatment period the apparent body burden was calculated to correspond to an actual dose of about 9-10 ng TCDD/kg body wt. Such an actual dose level might be assumed to be reached under steady-state conditions in chronic experiments with daily doses of about 135 pg TCDD/kg body wt (assuming a half-life for TCDD in the marmoset of 6-8 weeks). Extrapolations of the results obtained at higher doses to very low exposures is not justified with respect to the effects induced by TCDD on the immune system of marmosets. At lower doses the effect is clearly reversed. PMID- 1514924 TI - Plasma concentrations of pralidoxime methylsulphate in organophosphorus poisoned patients. AB - Using pharmacokinetic data from healthy human volunteers in a bicompartmental pharmacokinetic model, a repeated dose scheme for pralidoxime methylsulphate (Contrathion) was developed producing plasma levels remaining above the assumed "therapeutic concentration" of 4 mg.l-1. Using the same data, it was found that a concentration of 4 mg.l-1 could also be obtained by a loading dose of 4.42 mg.kg 1 followed by a maintenance dose of 2.14 mg.kg-1.h-1. In order to study the pharmacokinetic behaviour of pralidoxime in poisoned patients, this continuous infusion scheme was then applied in nine cases of organophosphorus poisoning (agents: ethyl parathion, ethyl and methyl parathion, dimethoate and bromophos), and the pralidoxime plasma levels were determined. The mean plasma levels obtained in the various patients varied between 2.12 and 9 mg.l-1. Pharmacokinetic data were calculated, giving a total body clearance of 0.57 +/- 0.27 l.kg-1.h-1 (mean +/- SD), an elimination half-life of 3.44 +/- 0.90 h, and a volume of distribution of 2.77 +/- 1.45 l.kg-1. PMID- 1514925 TI - The study of leucine and methionine transport in the gut of rats intoxicated with thiram. AB - The effects of thiram on amino acids transport in rats jejunum were investigated. Using the gut everted sac method it was shown that 4 weeks intoxication with the pesticide (5% DL50 per os daily) caused time dependent inhibition in transport of C14-leucine and C14-methionine in the rat jejunum. In order to obtain further information, the influx of both amino acids into the jejunum slices was investigated in rats treated with thiram for 2 weeks. Over a range of amino acid concentrations (0-20 mM) the influx of these compounds was defined as the sum of a saturable term (active transport) and a linear term (passive transport). It was shown that thiram affected only the active transport of amino acids. The analysis of this transport for leucine using Lineweaver-Burk plots showed a decrease of the half-saturation constant (Kt), while the maximal value (Jm) remained unchanged. In the methionine transport study both kinetic constants were changed. PMID- 1514926 TI - Loss of glomerular polyanion correlated with albuminuria in experimental cadmium nephropathy. AB - The relationship between proteinuria and glomerular polyanion (GPA) charge has been studied in a model of experimental cadmium (Cd) nephropathy. Female Sprague Dawley rats were administered Cd in drinking water for up to 18 months. From month 2, the animals showed an elevation of albuminuria preceding by about 6 months the rise of urinary beta 2-microglobulin and IgG. The nephrotoxic action of Cd was not readily detectable on the basis of the urinary output of beta-N acetylglucosaminidase, alanine aminopeptidase and lactate dehydrogenase. These enzymes showed either little variation or were affected late in the intoxication process. Administration of Cd for 12 or 18 months did not impair the GFR. The glomerular origin of the albuminuria induced by Cd was demonstrated by estimating the glomerular filtration of rat or human (injected intravenously) albumin in rats whose tubular reabsorption had been blocked by a saturating dose of cytochrome C. The GPA charge was assessed by measuring the binding of the cationic dye, Alcian blue (AB), to membranes of isolated glomeruli. The sialic and sulfate content of these membranes was also determined. The Cd induced albuminuria was negatively correlated (r = -0.73; n = 37) with the AB binding to glomerular membranes, their sialic acid content (r = -0.39) but not with their sulfate content (r = -0.15). A negative correlation (r = -0.62; n = 37) was also observed between the albuminuria and red blood cell membrane negative charges largely contributed by sialic acid. All these observations can be interpreted as the evidence that Cd enhances the glomerular filtration of proteins through a GPA depletion involving mainly sialic acid. PMID- 1514927 TI - Effects of exogenous factors on the cerebral glutathione in rodents. AB - Since glutathione is thought to be involved in cerebral functions, changes in the glutathione level imply modulations of the neurotransmission in addition to all the known effects of GSH. It was investigated whether alterations of the cerebral glutathione can be induced by consumption of GSH, by inhibition or stimulation of the synthesis of GSH, or by an inhibition of the re-reduction of the oxidized glutathione. Aminophenazone, propyphenazone, acetaminophen, phenytoin, morphine and nitrofurantoin, known to deplete hepatic GSH, had no effects on cerebral GSH. Diethyl maleate (0.6 ml/kg) decreased the cerebral content of GSH and GSSG in adult rats as well as in fetuses. The depletion of the cerebral GSH caused by diethyl maleate treatment for 4 days was followed by an increase up to 125% and a subsequent return to the normal level after 1 week. In rats starved up to 71 h deficiency of exogenous amino acids caused only a minimal or no decrease in cerebral GSH. The specific inhibitor of the gamma-glutamylcysteine synthetase BSO only depleted GSH in the brain of young mice following the repeated s.c. administration of a high dose (890 mg/kg). After cobaltous chloride (20 mg/kg; twice a day for 2 or 4 days) the GSH level in the brain was unchanged. In vivo inhibition of the cerebral glutathione reductase was caused by ammonium metavanadate (12.5 mg/kg; three times a week for 6 weeks). Nitrofurantoin (150 mg/kg) had no effect. After lomustine (10 mg/kg) a minimal increase in glutathione reductase was found, but simultaneously also an increase in GSSG and of the ratio GSSG/total glutathione. PMID- 1514928 TI - Effect of ten thiocompounds on rat liver DNA damage induced by a small dose of N nitrosodimethylamine. AB - The use in a chemoprevention study of high doses of the genotoxic agent might result in erroneous information because of possible nonlinearity of pharmacokinetic processes and toxicity-induced derangement of physiological defense mechanisms. According to these premises ten thiocompounds, potentially active as inhibitors of metabolic activation and/or scavengers, were examined for their capability of reducing the frequency of liver DNA lesions induced by a very small dose of N-nitrosodimethylamine (NDMA). This was accomplished by means of a viscometric technique previously found suitable to detect a minimal amount of DNA fragmentation. Rats were injected i.p. or i.v. with 1 mmol/kg of thiocompound, 0.2 mg/kg NDMA given by gavage 1 h afterwards, and killed for DNA damage assessment 14 h later. Statistically significant changes of viscometric parameters, which are considered indicative of a protective activity, were produced by disulfiram (DSF), and to a lower extent by diethyldithiocarbamate (DEDTC). Any modification of NDMA-induced DNA damage was absent in rats pretreated with glutathione reduced form (GSH) and dimethyl sulfoxide (DMSO). Allyl disulfide (ADS), L-cysteine (CYS), N-acetylcysteine (NAC), alpha mercaptopropionylglycine (MPG), ethylxanthic acid (PEX), and 2-mercaptoethane sulfonic acid (MESNA) increased in various degree the frequency of DNA-strand breaks. In subsequent experiments the protective activity of DSF was found to be dose-related, dependent on the time of administration, and greater by oral route. Taken as a whole, these results suggest that several putative anticarcinogens might be ineffective against the DNA-damage produced by the low doses encountered in human exposure. PMID- 1514929 TI - Experimental data from closed chamber gas uptake studies in rodents suggest lower uptake rate of chemical than calculated from literature values on alveolar ventilation. AB - Experimental data obtained in vivo with the closed-chamber gas uptake technique have been reported for a series of volatile chemicals. Pharmacokinetic analyses of these data have been performed either by using a two-compartment model or physiological models. In the former the transfer rate of chemical from ambient air to body is defined by the clearance of uptake. In the latter models the transfer rate depends on alveolar ventilation, cardiac output, and blood: air partition coefficient. In this communication we describe the quantitative relationship between clearance of uptake and alveolar ventilation, cardiac output, and blood: air partition coefficient. Theoretical values of clearance of uptake were calculated for a variety of volatile chemicals using literature data on alveolar ventilation, cardiac output, and blood: air partition coefficient. For most chemicals the experimentally determined values in rats and mice were about 60% of the theoretical values. This suggests that the inhalatory uptake rate of chemical may be overestimated if literature values of alveolar ventilation are used in physiological pharmacokinetic models for rodents. PMID- 1514930 TI - N1-(2-hydroxyethylthioethyl)-4-methyl imidazole (4-met-1-imid-thiodiglycol) in plasma and urine: a novel metabolite following dermal exposure to sulphur mustard. PMID- 1514931 TI - Accidental death caused by the absorption of 2,4-dichlorophenol through the skin. AB - A case involving an accidental fatality resulting from skin absorption of 2,4 dichlorophenol in a factory is presented. The compound was quantified using gas chromatography after separation on a SP-1240 DA column and detection with flame ionization. Confirmation was obtained with mass spectrometry. Blood concentration was 24.3 mg/l. Other drugs, including ethanol, were not detected. PMID- 1514932 TI - Old belief that gastrointestinal injury by the NSAID is due to direct contact. PMID- 1514933 TI - Histogenetic aspects of the composition and structure of human ectopic enamel, studied by scanning electron microscopy. AB - This study was made on 12 enamel projections and 12 enamel pearls on human permanent molars to compare their structure and composition, which might elucidate possible histogenetic differences between these two forms of ectopic enamel. The enamel projections contained approx. 2 (weight)% less Ca and P than control occlusal and mid-coronal enamel. Their mineralization was less homogeneous and probably defective. Their enamel structure was markedly irregular in the prismatic as well as the aprismatic layer, but the composition and structure were very similar to those of the control enamel close to cervical border. The enamel of the pearls largely corresponded in composition and structure to the control occlusal and mid-coronal enamel. The enamel of large pearls also resembled coronal enamel in its compositional and structural variability in the occlusal-cervical direction. These findings suggest that amelogenesis in enamel projections is a continuation of amelogenesis in the cervical region. In contrast, amelogenesis in enamel pearls follows the same pattern as that in a dental crown, from the occlusal region to the cervical enamel border. Therefore, the enamel pearl may well be regarded as an attempt at new tooth formation. PMID- 1514934 TI - The influence of morphological variation on Candida albicans adhesion to denture acrylic in vitro. AB - Using denture acrylic pieces coated with either whole human stimulated saliva or oral streptococci, the binding ability of three different Candida albicans strains was investigated. The C. albicans strains include a clinical isolate with the commonly observed, smooth, round colonial morphology (strain 613p), a morphological variant spontaneously derived from the clinical isolate strain 613p (strain 613m1BK) and a clinical isolate from an oral lesion that was also a morphological variant upon primary isolation (strain 228). Levels of adhesion to the acrylic pieces were determined radiometrically using C. albicans cells metabolically labelled with [35S]-methionine. Whole stimulated saliva significantly increased the binding of all strains compared to uncoated acrylic. However, the level of binding of strain 613p to saliva-coated acrylic was significantly greater than the levels observed for the morphological variant strain 613m1BK. Coating acrylic pieces with either Streptococcus sanguis NCTC 10904, Strep. mutans GS-5 or Strep. sobrinus ATCC 27352 instead of saliva resulted in significantly greater binding by strain 613p compared to uncoated acrylic. Pre-coating the acrylic with the oral streptococci did not significantly increase the binding of morphological variant strains 613m1BK and 228 compared to uncoated acrylic. In general, preincubation of adherent streptococci with sucrose to induce the synthesis of extracellular carbohydrate polymers did not significantly increase the binding levels of the C. albicans strains above those observed using streptococci in buffer alone. Compared to its parental strain 613p, morphological variant strain 613m1BK adhered poorly to denture acrylic coated with either salivary constituents or oral streptococci, while strain 228 adhered to the same substrates at an intermediate level. Furthermore, physical disaggregation of clusters of the morphological variant strain 613m1BK did not appear to increase its binding capacity to saliva-coated denture acrylic. The effect of whole stimulated saliva on the adherence of C. albicans 613p to a variety of plastic substrates in addition to denture acrylic was examined. Overall, saliva pre-coating of the various plastics promoted C. albicans 613p adhesion. The adhesion of strain 613p to denture acrylic coated with whole stimulated saliva from each of five different donors or with parotid and submandibular/sublingual saliva from each of two donors was also examined. Regardless of donor, a coating of whole stimulated saliva significantly increased the binding of strain 613p to denture acrylic compared to uncoated acrylic. In addition, a coating of parotid saliva significantly increased the binding of strain 613p to denture acrylic compared to submandibular/sublingual saliva. PMID- 1514935 TI - The correlation of temporal regulation of glycosaminoglycan synthesis with morphogenetic events in mouse tooth development. AB - The purpose of this study was to investigate the pattern of sulphated glycosaminoglycan synthesis during morphogenesis and cytodifferentiation in mouse tooth rudiments and to compare the results with those obtained in another study for salivary gland, a branched organ. Sulphated glycosaminoglycan was labelled by incubating molar rudiments from day 15 of gestation to day 1 post partum in medium containing [35S]-sodium sulphate. The rudiments were washed, homogenized and digested in pronase and then were sequentially digested by chondroitinase ABC and chemically degraded by nitrous acid oxidation. The fractions from each of these procedures were analysed by chromatography on Sephadex G-50 columns. The analysis revealed that, during morphogenesis, levels of chondroitin sulphate increased to a peak of 91% at day 18 and levels of heparan sulphate diminished to 8% during this period. As cytodifferentiation occurred, the level of chondroitin sulphate dropped to 64% and that of heparan sulphate increased to 35%. These results are similar to those reported for rat submaxillary gland, a branching organ. It appears that this pattern of sulphated glycosaminoglycan synthesis is not a unique feature of branching morphogenesis but may be one which marks the transition between morphogenesis and cytodifferentiation in non-branching rudiments as well. PMID- 1514936 TI - The effects of colony-stimulating factor-1 on tooth eruption in the toothless (osteopetrotic) rat in relation to the critical periods for bone resorption during tooth eruption. AB - The toothless (tl) rat is an osteopetrotic mutation characterized by a generalized skeletal sclerosis, reduced bone resorption, few osteoclasts and a total absence of erupted teeth. This mutation is not cured by bone marrow transplants from normal littermates. It is known that the skeletal defects in tl rats are greatly improved after treatment with colony-stimulating factor-1 (CSF 1). This investigation concerns the effects of CSF-1 on the development and eruption of the dentition of tl rats. Untreated tl rats had no erupted teeth by 56 days after birth, and the roots of incisors and molars were severely distorted by compression against bone. The apex of the mandibular incisor did not extend past the first molar and continued growth of its apical end produced odontoma like masses consisting of distorted dentine and enamel matrices. In addition, few osteoclasts were seen on alveolar bone surfaces surrounding the developing teeth. Mutants given CSF-1 were characterized by delayed eruption of all molars and sometimes incisors. The incidence of incisor eruption was related inversely to the age at which CSF-1 treatment began. Molars of treated tl rats had well developed roots similar to those in normal rats. Treated mutants had numerous osteoclasts in alveolar bone and well-developed haemopoietic marrow spaces in the mandible. Histochemical staining for both tartrate-resistant acid phosphatase and tartrate-resistant acid ATPase was reduced or negligible in osteoclasts of untreated tl rats, heavy in normal osteoclasts and of intermediate intensity in CSF-1-treated mutants.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1514937 TI - Transforming growth factor-beta 1 mRNA in neonatal ovine molars visualized by in situ hybridization: potential role for the stratum intermedium. AB - Human dentine contains relatively large amounts of transforming growth factor beta (TGF-beta), which might originate from odontoblasts. The expression of the TGF-beta 1 message in developing teeth was examined by in situ hybridization. The analysis was made on 5-microns serial sections of mandibular third molars of neonatal sheep cut from tissues that had been fixed in glutaraldehyde and paraffin-embedded. A 35S-labelled cRNA probe, complementary to TGF-beta 1 mRNA, was constructed from human TGF-beta 1 cDNA. Northern analysis of total RNA from sheep placenta and neonatal third molars demonstrated hybridization to a single 2.4 kb TGF-beta 1 transcript from both tissues, indicating cross-reactivity of the human probe in the sheep. In the neonatal molars, in situ hybridization was observed in cells of the inner enamel epithelium, mature ameloblasts and mature odontoblasts, but not within preodontoblasts before dentine matrix formation. TGF beta 1 mRNA expression was also evident in the cells of the dental papilla but scarcely so in the stellate reticulum. The most striking feature was the appearance of hybridization signal in the cells of the stratum intermedium before hybridization was evident in the inner enamel epithelium. Control sections incubated with RNAase before incubation with probe did not show evidence of hybridization. These findings suggest that TGF-beta 1 may have an important regulatory role in the differentiation of ameloblasts and odontoblasts, perhaps by modulating matrix formation during amelogenesis or odontogenesis. They also suggest a potential novel regulatory role for the cells of the stratum intermedium. PMID- 1514938 TI - Increase of microliths in inactive salivary glands of cat. AB - Secretory inactivity could be a factor in the formation of microliths, and so their occurrence in feline salivary glands after the secretory inactivity produced by parasympathectomy was investigated. Parasympathectomy was followed by a greatly increased occurrence of microliths in the submandibular salivary gland, but not in the parotid and sublingual, which may relate to residual secretory activity in these glands. This discovery suggests that secretory inactivity may indeed be a factor in the production of microliths in human salivary glands, and consequently of chronic sialadenitis and sialothiasis. PMID- 1514939 TI - The origin of short- and long-latency mylohyoid nerve responses elicited by high intensity electrical stimulation of intradental nerve in cats. AB - A double reflex response of the mylohyoid nerve to the jaw depressor muscles after electrical stimulation of the intradental nerves was recorded in cats anaesthetized with alpha-chloralose. The threshold value of the long-latency (16 19 ms) response was almost 20 times greater than that of the short-latency (5-8 ms) response. At the threshold intensity of the long-latency response, the short latency response with shorter latency appeared. After extirpation of the stimulated tooth pulp, the short-latency response with a lower threshold disappeared, whereas the short-latency response with a higher threshold and the long-latency response both persisted and showed no change in threshold or latency. These findings indicate that the low-threshold, short-latency response was due to excitation of pulpal nerve fibres, while the high-threshold, short latency response and the long-latency response were both due to excitation of extrapulpal afferent fibres as a result of the spread of current outside the tooth. PMID- 1514940 TI - The thickness of the sound and periodontally diseased human cementum. AB - Cementum of teeth previously analysed for fluoride was re-examined in order to determine whether or not periodontal disease had affected the thickness of the tissue. In the periodontally diseased teeth the cementum was thinner than normal in the middle region of the root. The apical cementum, however, was significantly thicker in periodontally diseased than in the sound teeth of subjects over 60 yr old. This may account for the higher total fluoride levels previously reported in the apical cementum of these same teeth. PMID- 1514941 TI - The hearing loss in Wegener's granulomatosis: relationship between hearing loss and serum ANCA. AB - We observed the change of hearing for 1 year in a patient with Wegener's granulomatosis. We also studied anti-human neutrophil cytoplasm antibody (ANCA), which is believed to be specific for this disease and to be associated with disease activity. From these progresses, changes in hearing were considered to be generally related with the general condition and with the ANCA titer level. Because hearing loss in our case was improved by steroids and immunosuppressants, and because ANCA is the autoantibody observed in angiitis syndrome, hearing loss in this case of Wegener's granulomatosis was suspected of being caused by angiitis of the middle and inner ear induced by autoimmune reaction. PMID- 1514942 TI - Interlay method for myringoplasty. AB - Sixty-nine ears with perforation of the tympanic membrane were reviewed. All had undergone myringoplasty by the interlay method. The average period for complete epithelization was 16.1 days after surgery. Neither blunting of the anterior tympanomeatal angle nor lateralization of the tympanic membrane was observed. The success rate was 94.2% for the initial surgery, when "success" is defined as closure of the perforation and complete epithelization (dry ear). The surgical technique and various advantages of the interlay method of myringoplasty are described. PMID- 1514943 TI - Importance of atticotomy in chronic otitis media with fixation of ossicles. AB - Seventy-seven patients with chronic otitis media were reviewed. Of the 77 patients, 42 underwent tympanoplasty with a columella, and 35 underwent myringoplasty and atticotomy. Twenty-five of the latter 35 patients showed less than 10 dB of hearing improvement with a patch test before operation. The ossicular chain was not disconnected in any of the 25 patients, but the mobility was severely restricted. It was interesting that fixation of the malleus was found at surgery in 80% (20/25) of the patients, whereas the stapes was immobilized in only 16% (4/25). Myringoplasty and atticotomy instead of tympanoplasty with a columella was sufficient to achieve hearing improvement in most of such cases. However, conventional atticotomy was not able to achieve improvement in the mobility of the ossicles because the mobility is usually severely restricted at the malleus. Removal of the anterior tympanic spine is the key to recovery of the mobility of the malleus, resulting in hearing improvement. Rate of success was obtained in 24 of 25 ears (96%). PMID- 1514944 TI - Four cases of metastatic lymphoma into the temporal bone. AB - A histopathological study on 17 temporal bones obtained from 9 patients who died of malignant lymphoma revealed metastasis of malignant lymphoma in 7 temporal bones from 4 of them. There were no differences in stages at the initial diagnosis between the cases with metastasis and those without metastasis. However, the higher was the frequency of metastasis, the longer became the period from the first medical examination to death. In addition, malignant lymphoma was considered to metastasize into the temporal bone by the following two routes, 1) direct infiltration or invasion from the cerebrospinal fluid and 2) hematogenous metastasis or invasion. PMID- 1514945 TI - The place of conservation surgery for T3 laryngeal carcinomas with fixation. AB - Although the traditional surgical treatment of T3 laryngeal carcinomas is total laryngectomy, we have obtained favorable survival results for selected cases with partial laryngectomy, as exemplified in the literature. Extending the indications up to ultimate limits by partial, but radical surgical techniques is the recent trend in the world, for the conservation surgery of laryngeal cancers. The primary treatment of T3 laryngeal cancers, instead of irradiation, should be surgical and, for select cases partial laryngectomy, depending on laryngeal embryological development and lymphatic drainage, may be carried out. We have performed partial laryngectomy with elective or therapeutic and radical or modified radical neck dissection for 43 T3 laryngeal carcinomas at the Department of Otolaryngology, Istanbul Medical Faculty, University of Istanbul in the years 1978-1991 and obtained 2, 3, and 5 years of survival rates, which are 89, 79.4, and 73%, respectively. PMID- 1514946 TI - Surgical treatment of large epiglottic cysts with a side-opened direct laryngoscope and snare. AB - Two cases of large epiglottic cysts are reported. Histopathological examination revealed a retention cyst in one case and an epidermoid cyst in the other. We designed a side-opened direct larngoscope and snare for treating epiglottic cysts. This direct laryngoscope is characterized by an opening from the anterior tip to the posterior end of the right side. The removal of the cysts was accomplished by using this direct laryngoscope and a snare under inhalation anesthesia by fiber optic guided endotracheal intubation. The side-opened direct laryngoscope enabled easy insertion of the snare through the right side opening. PMID- 1514947 TI - A case of delayed endolymphatic hydrops. AB - A 30-year-old male with delayed endolymphatic hydrops was given a sac operation. An intradural portion of the endolymphatic sac was resected and the epithelial surface was examined under a scanning electron microscope. The epithelium showed fibrous degeneration and disappearance of the epithelial cells. Pathogenesis of degeneration of the endolymphatic sac is discussed. PMID- 1514948 TI - A case of pharyngolaryngeal stenosis in Behcet's disease. AB - A rare case of pharyngolaryngeal stenosis in Behcet's disease is reported. A 44 year-old female who had Behcet's disease for 13 years complained of dysphagia and dyspnea, and was referred to our hospital for treatment in May 1988. The bilateral meso-hypopharyngeal walls were swollen, and the epiglottis was edematously folded, occluding the larynx. Epiglotectomy and thyrohyoidpexia were performed, with dysphagia and dyspnea disappearing after the operation. Two years after the operation, dysphagia and dyspnea recurred because of two stepped cicatricial stenoses at the mesopharynx. An enlargement operation, incising the pharyngeal cicatricial tissue bilaterally and covering raw surfaces with free skins and the pedunculated cervical flap, was performed. Colchicine, corticosteroid, and tranilast (anti-allergy drug) were administered to prevent re stenosis. Stenosis was not observed for 10 months after the second operation. Two cases undergone surgical interventions have been reported, and this is the first case reporting long term result of the surgical procedure. Because the skin and mucosa of patients with Behcet's disease shows hyperreactivity to stimuli, the choice of surgical procedure is controversial and recurrence of stenosis is possible. PMID- 1514949 TI - Effects of prostaglandin E2 on the fluctuating hearing loss in Meniere's disease. AB - To elucidate the possible mediating role of prostaglandins as underlying mechanism of the acute audiologic effects of furosemide in patients with Meniere's disease, the hearing threshold shift after a 1 hour infusion of a commercially available prostaglandin E2 derivative (120 ng/kg body weight) was determined in 10 patients. Prostaglandin E2 produced a transient hearing improvement comparable to the effects obtained in the furosemide test with 1.2 mg/kg bw in the same patients. The effectiveness of a prostaglandin infusion on hearing levels may be a further sign of the involvement of this mediator in hearing processes. PMID- 1514950 TI - Exercise, oxidative damage and effects of antioxidant manipulation. AB - Exercise induces free radical formation in muscle and liver, and oxidative damage, such as lipid peroxidation. The amount of damage depends on exercise intensity, training state and the tissue examined and can be reduced through dietary supplementation of antioxidants such as vitamin E and possibly coenzyme Q10. Supplementation with antioxidants does not increase maximal aerobic capacity or maximal exercise capacity; effects on endurance capacity are unclear. Deficiency of vitamin E or vitamin C greatly reduces endurance capacity, whereas selenium deficiency has no effect on endurance capacity. In studies by the authors, urinary output of the oxidatively damaged RNA base 8-hydroxyguanosine was not affected by several submaximal exercise bouts nor by supplementation with vitamins E and C and beta-carotene in moderately trained humans. In rats, endurance training caused an increase in oxidative damage, as measured by the protein carbonyl concentration of muscle, but not liver. Muscle protein carbonyl concentration returned to normal on detraining. These results indicate that the search for oxidative damage due to exercise and the effects of antioxidant manipulation on such damage should ideally involve examination of several indices of oxidative damage in various tissues after exercise and training. PMID- 1514951 TI - Tube feeding-related diarrhea. PMID- 1514953 TI - Nicotine cessation, mania, and depression. PMID- 1514952 TI - Three ways of abolishing automaticity in sinoatrial node: ionic modeling and nonlinear dynamics. AB - A review of the experimental literature reveals that there are essentially three qualitatively different ways in which spontaneous activity in the sinoatrial node can be abolished. We show that these three ways also occur in an ionic model of space-clamped nodal membrane. In one of these three ways, injection of a current pulse abolishes ("annihilates") spontaneous action potential generation. In the other two ways, as some parameter is changed, one sees a sequence of qualitative changes in the behavior of the membrane as it is brought to quiescence. In one of these two ways there are incrementing prepotentials intermixed with action potentials, with a maintained small-amplitude subthreshold oscillation being the limiting case of such behavior. Thus both experimental and modeling work indicate that the number of ways in which spontaneous activity can be abolished, or initiated, in the sinoatrial node is limited. The classification into three ways is based on ideas drawn from the qualitative theory of differential equations, which are introduced. The classification scheme can be extended to encompass behaviors seen in other cardiac oscillators. PMID- 1514954 TI - Insidious renal failure. PMID- 1514955 TI - Firearm homicide among black teenage males in metropolitan counties. Comparison of death rates in two periods, 1983 through 1985 and 1987 through 1989. AB - OBJECTIVE: To identify US counties (1) that had either significantly high or significantly low firearm homicide rates among black males 15 through 19 years of age in 1983 through 1985 and in 1987 through 1989, and/or (2) that experienced a significant increase in the firearm homicide rate between 1983 through 1985 and 1987 through 1989. DESIGN: Using the Compressed Mortality File, a county-level mortality and population database maintained by the National Center for Health Statistics, Centers for Disease Control, Hyattsville, Md, county-level firearm homicide rates are analyzed. SETTING: Eighty counties with a population of at least 10,000 black males 15 through 19 years of age in 1987 through 1989. SUBJECTS: Black males 15 through 19 years of age whose underlying cause of death was classified as firearm homicide (E965.0 through E965.4, or E970) in the ICD-9 (International Statistical Classification of Diseases, Injuries, and Causes of Death, Ninth Revision). MAIN OUTCOME MEASURE: County-specific firearm homicide rate. RESULTS: In 1983 through 1985 and in 1987 through 1989, seven and 13 counties, respectively, were identified that had significantly high firearm homicide rates. Firearm homicide rates were significantly high in both time periods in the following counties: Los Angeles, California; Wayne, Michigan; Kings, New York; St Louis City, Missouri; and Baltimore City, Maryland. Firearm homicide rates increased significantly between 1983 through 1985 and 1987 through 1989 in 34 of the 80 counties. Twenty counties had significantly low rates in both time periods. Several counties with low rates in 1983 through 1985 experienced significant increases and by 1987 through 1989 were among those with high rates. CONCLUSIONS: Surveillance of firearm homicide rates at the county levels in counties with high and with low rates is a necessary first step in the development of successful violence prevention programs. Those counties where rates are high and increasing are the counties that are in greatest need for intervention strategies. Knowledge of the incidence of nonfatal firearm injuries is also needed. PMID- 1514956 TI - Vitamin E moves on stage in cancer prevention studies. PMID- 1514957 TI - Effects of running training on the blood glucose and lactate in rats during rest and swimming. AB - The purpose of this study was to examine the effect of physical training on the concentrations of glucose and lactate in the blood of rats during rest and after an acute bout of exercise. We used the following types and periods of training; (i) swimming for 4 weeks, (ii) running for 4 weeks, and (iii) running for 10 weeks. The results clearly show that the resting levels of blood glucose was significantly lower in groups trained by either swimming or running than untrained groups. In addition, after the acute exercise of swimming, animals trained by either running or swimming showed a lower increase in the blood lactate than untrained animals. Furthermore, the increases in the blood glucose after swimming were significantly lower in the group trained by swimming for 4 weeks and by running for 10 weeks than in untrained groups. These results suggest that after physical training by running, animals show an adaptation in the changes in the blood glucose and the blood lactate that are induced by a different type of physical stress, swimming. PMID- 1514958 TI - The human cDNA sequence homologous to the mouse MHC class I promoter-binding protein gene contains four additional codons in lymphocytes. PMID- 1514960 TI - The improved results of liver transplantation. PMID- 1514959 TI - Delimitation of cohesive ends site (cos) of Streptomyces temperate bacteriophage R4. AB - The cohesive ends site (cos) of actinophage R4 was delimitated by assaying the in vivo packaging activity of cosmid derivatives in Streptomyces lividans. A region of 66 bp from -30 to +36 from the center of cohesive ends was required for the basal level of packaging activity. Two additional regions outside the basal sequences from -39 to -31 and from +37 to +97 were necessary for the high level of activity, defined as the accessory sequences. Direct- or inverted-repeat sequences were found within the delimitated region, which might be involved in the recognition by the terminase of actinophage R4. PMID- 1514962 TI - Acute rejection in kidney grafts with delayed onset of graft function. A duplex Doppler study. AB - Forty-five kidney transplant recipients with delayed onset of diuresis due to acute tubular necrosis (ATN) were examined with duplex ultrasonography (DU). Resistive index (RI) was measured on the 4th post-transplant day. Eleven grafts (24%) developed acute rejection. Mean RI prior to rejection of the 4th postoperative day in these grafts was 0.97 and in the 34 grafts which did not develop rejection mean RI was 0.82. There were 2/26 rejections (8%) in the group of grafts with an initial RI below 0.9 and 9/19 rejections (47%) in the group of grafts with RI of 0.9 or above on the 4th post-transplant day. Six months postoperatively there were 2/26 nonfunctioning grafts in the group with lower initial RI values (less than 0.9) and 6/19 nonfunctioning grafts in the group with higher indices (greater than or equal to 0.9). In nonfunctioning grafts a high initial RI (greater than or equal to 0.9) indicates that these grafts will be prone to developing acute rejection. PMID- 1514961 TI - Clinical application of arterialization of portal vein in living related donor partial liver transplantation. AB - Arterialization of the portal vein was employed during hepatic arterial reconstruction in our first few clinical experiences of partial liver transplantation using liver grafts obtained from living related donors. This procedure reduced the time required for revascularization of the grafts to about 25 min, and could in fact reduce the ischemic phase of the grafts. Repeated practice of the clinical transplantation technique has shortened the time needed to complete vascular reconstruction, eliminating the need for this procedure in most of our subsequent cases. In many clinical cases, however, there may be emergency situations which require vascular reconstruction, resulting in a prolongation of ischemic phase and the deterioration of the cellular viability of the graft. In such situations, arterialization of the portal vein can be a useful way to prevent the prolongation of the ischemic phase and to rescue the graft. PMID- 1514964 TI - Low-temperature fluorometric technique for evaluating the viability of rat liver grafts after simple cold storage. AB - Time-dependent changes in the viability of rat liver graft during cold preservation with Euro-Collins solution were evaluated with NADH fluorometry. Correlation between the fluorometric analysis, 1-week survival rate after liver transplantation, and mitochondrial ATP synthesis activity in the early phase after transplantation was studied. Fluorometric study: Rat livers were preserved at 0 degree-4 degrees C for 0-48 h in Euro-Collins solution and then reperfused for 15 min with oxygenated Krebs-Henseleit solution at 4 degrees C. The amplitude (R x A) between the oxidized and the reduced steady-state NADH fluorometric trace and the velocity (R x V) of the trace were determined to evaluate the mitochondrial respiratory chain. The R x A and R x V remained at levels higher than 90% of control after 6-h preservation, while the R x A of the 9-h preservation group and the R x V of the 12-h preservation group decreased significantly compared with those of the control and the 6-h preservation group. Survival study: a 100% survival rate after transplantation was achieved in the 6 h preservation group, whereas the rates were 18.8% and 0% in the 9- and 12-h preservation groups respectively. These survival rates correlated closely with the time-dependent decrease of the fluorometric parameters. Study of mitochondrial phosphorylative activity and energy charge 3 h after transplantation: With fresh grafts, the decrease in hepatic energy charge after transplantation was reduced to 0.79 from the control value of 0.86 by a 30% increase in mitochondrial ATP synthesis ability.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1514963 TI - Multifactorial analysis of the outcome of 6430 cadaver kidney grafts. AB - A total of 6430 cadaver kidney grafts performed within the network of France Transplant between 1 January 1978 and 1 January 1989 were analyzed. Each case was examined comprehensively in regard to 12 variables. A multifactorial analysis (Cox regression) was used to determine the degree of association between each covariate and the outcome of the graft. The results were evaluated by calculating relative risks of graft failure for each variable. A total of seven covariates appeared to influence graft survival significantly: the period of transplantation (P = 10(-8)), retransplantations (P = 0.003), age and sex of the donor (P = 0.003 and 0.009 respectively), duration of pretransplant dialysis (P = 0.03), pretransplant sensitization to HLA antigens (P = 0.05), and matching for HLA-A, B, and -DR loci (P = 0.03). This last parameter has previously been reported as influencing the outcome of the graft in seven out of eight international studies carried out using similar methodology. PMID- 1514965 TI - Intestinal allograft survival in the rat following pretreatment with donor specific UV-B-irradiated leukocytes and peritransplant immunosuppression with cyclosporine. AB - Previous studies from our laboratory showed that pretreatment with ultraviolet-B irradiated donor leukocytes (UV-B DL) combined with brief peritransplant cyclosporine (CyA) resulted in indefinite survival of Wistar/Furth rat cardiac allografts in Lewis recipients. This study was designed to examine the effect of pretransplant UV-B DL with or without peritransplant CyA on orthotopic intestinal allografts in the same rat strain combination. The results showed that while low dose CyA treatment alone (10 mg/kg i.m. on days 0, +1, and +2) had no effect on intestinal allograft rejection, 20 mg/kg (on days 0, +1, and +2) CyA significantly (P less than or equal to 0.001) prolonged graft survival, with 33% of the hosts surviving indefinitely. The highest dose of CyA (30 mg on days 0, +1, and +2) abrogated rejection, but most transplant recipients succumbed to infection and functional ileus due to a toxic side effect of CyA. Pretreatment with UV-B DL on days -14 and -7 alone did not prolong intestinal allograft survival. Combination of a subtherapeutic CyA dose (20 or 10 mg/kg) given on days 0, +1, and +2 with pretransplant UV-B DL on days -14 and -7 did not alter the survival of intestinal allografts compared to treatment with CyA alone. This suggests that pretreatment with UV-B DL with or without peritransplant administration of CyA has no effect on intestinal allograft survival, in contrast to the effect of such combined treatment on cardiac allograft survival, where indefinite graft survival is observed.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1514967 TI - Successful renal transplantation in a patient with familial lecithin:cholesterol acyltransferase deficiency. PMID- 1514966 TI - A chronicle of organ transplant progress in Japan. AB - This study records the progress of organ transplantation in Japan by reviewing significant developments in five areas: actual transplant legislation; landmark cases notably affecting public impressions of organ transplants; efforts to establish brain death criteria; action on the part of the Japan Medical Association; and current attempts to legislate on brain death. The account demonstrates how the notions of both brain death and heart transplantation have met with strong resistance. The first and only heart transplant occurred in 1968. Through its historical emphasis, this report reveals that, although opposition has not impeded transplant research, the determination of death and the idea of heart transplants remain highly controversial due to specific religious, philosophical, and cultural factors. PMID- 1514968 TI - Health promotion and chronic illness. Discovering a new quality of health. PMID- 1514969 TI - Coping with the stress of illness. AB - How can we cope better, or help others to do so? The answer to this depends on knowing what an individual is coping with. This, in turn, depends on the appraisal, by the individual concerned, of the significance of what is happening for well-being--in effect, the source of harm, threat, challenge. Cases of myocardial infarction, cancer and chronic pain have some harms, threats, and challenges in common but there are also unique factors in each illness. The patient with a chronic illness is continually appraising his or her symptoms, pains, disease progression with respect to their significance for well-being and survival, and coping accordingly. The paper presents a microanalytic, contextual and process-centred approach to coping which is part of a broad system of thought, emphasizing cognitive appraisal and the person's ongoing relationships with the environment as factors of his or her emotional life. Implications for prevention and treatment of illness in a perspective of health promotion are discussed as well as the need for research to predict long-term outcome from stress and coping. PMID- 1514970 TI - Emerging forces in cancer care. AB - The mainstream of scientific research is moving towards increasing recognition of the limits of conventional therapies and cautious optimism about the potential for new biological therapies. This situation has given rise to a social phenomenon among cancer patients. Today, in many parts of the world, a significant minority has chosen to engage actively in the fight for recovery. This minority searches for an intelligent integration of efficacious conventional therapies and complementary therapies involving personal trials of intensive health promotion. These trials cover nutritional, psychological, and immuno modulating approaches to supporting general health. It appears that 10% among those patients achieve exceptional results, another 10% fail, and 80% become "healthy" cancer patients. While these experiences raise many interesting clinical, scientific and policy questions, they have provided a growing body of evidence that a great deal can be done with behavioural approaches, not in terms of sweeping cures but possibly for some gains in life extension and certainly for great gains in the human experience of being healed (or "becoming whole" with cancer). PMID- 1514971 TI - Conceptual views on quality of life. AB - Quality of life can be discussed in many ways. One way is to analyse the empirical quantitative approach to determine whether the research categories are operational, empirically unambiguous, and thematically relevant; progress, in the sense of changing the number of research categories, does not take place through a systematic empirical test but through a modification of the theory of quality of life. The current debate on quality of life has included a conflict between natural science and a humanistic approach. Our view is that quality of life must be defined through the difficult concept of happiness. When cancer threatens happiness, not one but two fundamental crises influence quality of life, which we regard as a key concept of a therapeutic method. PMID- 1514972 TI - The care of chronic pain patients. PMID- 1514973 TI - Pain: a kaleidoscope of ideas, concepts and approaches. AB - The following pages contain summaries and short statements on chronic pain providing further material for reflection and debate, namely: a) synopses of recent findings on: the physiology and biochemistry of pain; the contribution of psychoneuroimmunology; b) some views on a sociology of pain; c) analysis of various concepts and approaches which consider pain as: a symptom of disease a form of behaviour a psychosomatic reaction and a social learning process a communication phenomenon a symptom of disintegrated life a disruption in the integrity of the system a signal of broken unity a breach in the wholeness of the individual; d) a holistic approach in pain therapy; e) some unanswered questions. PMID- 1514974 TI - Canada's framework for health promotion and chronic illness. AB - At the first International Conference for Health Promotion, Canada presented "Achieving Health for All: A Framework for Health Promotion". This document reflects current thinking and proposes a conceptual base for the analysis of contemporary and emerging health issues. The approach is founded on the principles of health promotion developed by the World Health Organization and assimilates the themes which subsequently emerged in the Ottawa Charter. As such, Canada's framework presents a context for discussing chronic illnesses and for identifying opportunities that will lead to an intersectoral course of action. The salient features of this framework (Fig. 1) are briefly discussed. PMID- 1514975 TI - The gradual process of resuming work. PMID- 1514976 TI - A ten-point plan for meeting carers' needs. AB - The needs of people requiring extra care--people who are elderly, chronically ill or disabled--are now gaining long overdue recognition. Yet the somewhat different needs of those who look after them at home--known as "carers"--remain largely ignored. Two years ago, representatives of a group of organizations in Britain joined together to commission a project to redress this balance. They were concerned both to set out the range of carers' needs and to issue guidance on the kinds of services necessary to meet them. These documents, prepared following extensive consultation with people working in the field, have now been published (Richardson et al, 1989). This short article provides a brief overview of the issues. PMID- 1514977 TI - The workplace and the community. PMID- 1514978 TI - A "heart group" in the work setting. PMID- 1514979 TI - Healthy foods. PMID- 1514980 TI - Chronic illness: a media perspective. AB - The media can play a major role in creating supportive environments. They influence the man in the street as well as the decision-maker. They help set norms; they contribute to fostering community action. The information they transmit carries prestige. Health workers know this. They realize the power of communication. But seldom do they know how to approach media professionals and to provide them with what they need most: adequate, to-the-point and lively information. This paper provides them with useful guidelines on how to develop effective cooperation with the media and "help the media to help them" transmit the health message and create supportive environments. PMID- 1514981 TI - Families and self-help groups as key actors. PMID- 1514982 TI - The Munich Health Park. PMID- 1514983 TI - "Take heart": former heart patients form support groups. PMID- 1514984 TI - Place of residence as a health resort for rheumatic patients. AB - This paper deals with institutional aspects of health promotion in relation to a research programme comprising five projects currently in operation in various regions of the Federal Republic of Germany. The aim of these projects, which are supported at the federal level, is to provide locally based, interdisciplinary care for rheumatic patients throughout the course of the disease. Different organizational means are applied by the different projects to realize these goals. The project described here started in 1985 in Unna, a small town of some 60,000 inhabitants located in the Ruhr area. It involves intensive efforts in health promotion, the aim being to firmly establish self-help activities in everyday life. The following gives an overview of the project, its objective, structure and programme--especially the "cure seminars" organized on an outpatient basis--and some of the difficulties encountered with regard to practical implementation and the long-term provision of health-oriented care. The last part of the paper deals with the research component of the model. PMID- 1514985 TI - No-one need be alone with cancer. PMID- 1514986 TI - An education programme for patients with chronic pain. PMID- 1514987 TI - Clay modelling as an integrative therapy. PMID- 1514988 TI - Coping with the pain of chronic polyarthritis. PMID- 1514989 TI - Psychophysiological therapy for migraine sufferers. PMID- 1514991 TI - A new form of therapy for heart patients. PMID- 1514990 TI - Visualization in cancer group therapy. PMID- 1514992 TI - "Healthy ill people": social cynicism or new perspectives? PMID- 1514993 TI - The Feldenkrais method: awareness through movement. PMID- 1514994 TI - A health diary for the chronically ill. PMID- 1514995 TI - Medical training: a serious deficit. PMID- 1514996 TI - Training: needs and possibilities. PMID- 1514997 TI - A new approach to medical education. PMID- 1514998 TI - Health promotion for health professionals. PMID- 1514999 TI - Developing professional knowledge and skills. PMID- 1515001 TI - The quality of life of cancer patients. PMID- 1515000 TI - Effects of contact between cancer patients on their psychosocial problems. PMID- 1515002 TI - Common concepts in conventional and complementary medicine. PMID- 1515003 TI - Ayurveda: a long tradition of prevention. PMID- 1515004 TI - Helping the patient sing his own song. PMID- 1515006 TI - The Commonweal Cancer Help Program. PMID- 1515005 TI - The duo-formula. AB - This paper describes research on innovative ways to promote the practice of self care by people with a chronic complaint. Considerable interest in the subject exists, as confirmed by interviews with patient groups and with a random sample of general practitioners, specialists and community nurses. The answers, however, reflected some uncertainty regarding how to carry out self-care effectively. The study reported here is part of a wider programme of research on the area between conventional health care and self-care, including the development of training programmes for medical professionals and lay people. PMID- 1515007 TI - An interdisciplinary approach to pain therapy. PMID- 1515008 TI - Psychological treatment in medical practice. PMID- 1515009 TI - What do the patients think? PMID- 1515010 TI - A call to all those with responsibility. PMID- 1515011 TI - A dynamic vision of health. PMID- 1515012 TI - The rehabilitation process: issues and innovative approaches. PMID- 1515013 TI - Effecting institutional change. AB - The paper deals with the need for institutional change and behaviour change in the medical care and social security system of the Federal Republic of Germany. The data reported are from the Oldenburg Longitudinal Study (OLS), in which a thousand males suffering from a first myocardial infarction have been surveyed with mailed questionnaires five times in five years. In this study, special emphasis has been given to the influence of social support from the spouse, the medical care system, and workmates on the coping process. Special emphasis has been given as well to institutional factors and organizational problems in the rehabilitation system of general practitioners, rehabilitation clinics and the social security system. The paper concludes that there is a clear need for comprehensive services and other measures that promote self-reliance and self help activities among patients and their relatives. In the literature on heart disease, "health promotion" is mostly defined as behavioural change on the part of the individual--i.e. patients or members of what is conventionally called a "higher risk group". In this paper, however, I shall concentrate on another aspect which is no less important: the need for institutional change and behavioural change in the medical care and social security systems. This change, I argue, is needed in order to promote the health of patients who survived a first myocardial infarction. PMID- 1515014 TI - Enhancing health potential. PMID- 1515015 TI - Health promotion and cancer care. PMID- 1515016 TI - Immunological characterization of the guanine-nucleotide binding proteins Gi and Go in rat islets of Langerhans. AB - Inhibition of insulin secretion from rat islets of Langerhans is known to involve at least one pertussis toxin-sensitive guanine-nucleotide binding (G) protein. We have used antisera raised against unique antigenic determinants of different members of the family of pertussis toxin-sensitive G proteins to identify these proteins in rat islets. Antiserum SG1, which recognizes both Gi1 and Gi2, reacted with an islet protein having an approximate Mr of 40,000. Antiserum I1C (Gi1 specific) failed to recognize any islet proteins, suggesting that Gi2 is present in much greater amounts than Gi1. Indeed, Gi1 levels were below the detection limit of a sensitive immunogold/silver-staining method, indicating that it may be absent from the cells of rat islets. Two different antisera were used to identify Go-like G proteins in rat islet homogenates. Both antisera reacted with a protein band which, under appropriate conditions, could be resolved to reveal two separate proteins of Mr 39-40,000. Thus, at least two molecular forms of Go are present in rat islets. Subcellular fractionation indicated that all three G proteins identified in this study (Gi2 and two forms of Go) are localized to islet membranes. No immunoreactivity could be detected in the cytosolic fraction. PMID- 1515017 TI - Interleukin-1 beta stimulates growth of adrenocortical cells in primary culture. AB - Using tritiated-thymidine incorporation as a measure of cell growth, interleukin 1 beta stimulated the growth of bovine zona fasciculata/reticularis adrenocortical cells after 72 h in primary culture. Within the range of 10-1000 pg/ml, interleukin-1 beta produced over 40% of angiotensin II-stimulated [3H]thymidine incorporation (P less than 0.005 compared with basal for 10 pg/ml and 1000 pg/ml; P less than 0.05 for 100 pg/ml; two-tailed unpaired Student's t test). Interleukin-1 beta did not directly stimulate cortisol secretion. By stimulating adrenocortical growth, the increase in interleukin-1 during fever provides a potential mechanism for chronically raising glucocorticoid output. This study is the first demonstration of a long-term effect involving interleukin 1 beta on the adrenal cortex. PMID- 1515019 TI - Stimulation of insulin release by vasopressin in the clonal beta-cell line, HIT T15: the role of protein kinase C. AB - We have studied the effects of vasopressin and tetradecanoyl phorbol acetate (TPA) on cytosolic free Ca2+ ([Ca2+]i) and insulin release in HIT-T15 beta-cells. Saturable binding of [3H] [Arg8]-vasopressin to HIT cell microsomes indicated a single class of receptors with a dissociation constant (Kd) of 2.5 nM and a total number of binding sites (Bmax) equal to 120 fmol/mg protein. [Arg8]-vasopressin (0.1-100 nM) elicited dose-dependent insulin release from HIT cells by up to 25 fold. This increase was dependent on the presence of extracellular glucose and was blocked by omission of extracellular Ca2+ or addition of verapamil. The stimulation was biphasic; a rapid but short-lived large increase in release was followed by a smaller sustained rise. Vasopressin also evoked a marked, concentration-dependent increase in [Ca2+]i which was also biphasic; an initial spike was followed by a sustained elevation. This increase also required glucose and was blocked by the absence of extracellular Ca2+ or the addition of verapamil. Pretreatment of the cells with TPA overnight to deplete protein kinase C activity did not affect the [Ca2+]i or insulin responses to vasopressin. However, short-term exposure to TPA markedly reduced glucose-induced steady-state [Ca2+]i, despite potentiating glucose-stimulated insulin release sevenfold, and blocked the [Ca2+]i increase induced by vasopressin. These inhibitory effects of TPA were absent in protein kinase C-depleted cells and were prevented by staurosporine. TPA had no significant effect on vasopressin-induced insulin release. Vasopressin did not modify the activity of ATP-sensitive K+ channels.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1515018 TI - Expression of a human thyrotrophin receptor fragment in Escherichia coli and its interaction with the hormone and autoantibodies from patients with Graves' disease. AB - Graves' disease is an autoimmune thyroid disease characterized by the presence of pathogenic autoantibodies to the TSH receptor (TSH-R). By using polymerase chain reaction, the extracellular region of the human TSH-R cDNA has been amplified and used to prepare recombinant TSH-R (extracellular) protein fused with glutathione S-transferase (GST). Purification of the recombinant TSH-R (extracellular)-GST fusion protein was achieved by preparative gel electrophoresis in SDS or by preparative isoelectric focusing in urea. Following removal of SDS by detergent exchange or urea by dialysis, the purified recombinant receptor preparations were assessed for binding to the hormone or to autoantibodies from Graves' disease patients. The purified recombinant receptor preparations fail to show any binding to the hormone or autoantibodies either by inhibition of binding assays or by immunoblotting. The results imply that the correct folding and/or post translational modifications of the polypeptide chain which are not achieved in recombinant proteins produced in Escherichia coli may be important for the binding of the hormone or Graves' disease autoantibodies to the TSH-R. The recombinant receptor prepared in this manner will be useful for immunological and cellular investigations in patients with Graves' disease. PMID- 1515020 TI - Recombinant mouse prolactin: expression in Escherichia coli, purification and biological activity. AB - Transformation of Escherichia coli cells with a recombinant plasmid containing modified mouse prolactin (mPRL) cDNA and a pKK223-3 vector resulted in efficient expression of mPRL protein. Cloned mPRL cDNA was modified by removing the 5' non translating sequence as well as the sequence which encoded the signal peptide of preprolactin for recombination. In addition, approximately 100 nucleotides of the 5'-terminal region of the cDNA, which include the ATG initiation codon and the following 31 codons of mature mPRL, were replaced by a chemically synthesized oligonucleotide duplex. The sequence of this duplex was chosen to be rich in AT without changing the amino acid sequence of the protein. The modified cDNA was finally inserted into the multicopy plasmid, pUC19, before high-level expression of mPRL in E. coli cells was obtained. Western blotting analysis of total protein from transformed E. coli cells showed that both 23 and 16 kDa peptides were recognized by specific mPRL antisera. The purified and refolded 23 kDa protein exhibited a growth-stimulating effect on rat Nb 2 Node lymphoma cells, and was very similar to that of natural pituitary PRL. PMID- 1515021 TI - Characterization of an ovine glucocorticoid receptor cDNA and developmental changes in its mRNA levels in the fetal sheep hypothalamus, pituitary gland and adrenal. AB - Fetal sheep tissues possess glucocorticoid receptors (GR), and these change in number during the last two-thirds of gestation. There is, however, no information about developmental changes in tissue GR mRNA levels which might account for alterations in fetal GR content. We have therefore cloned and sequenced a 942 bp GR cDNA from a sheep liver cDNA library, and used it to study the relative abundance of GR mRNA in fetal and neonatal sheep tissues. Analysis of the cDNA revealed a partial sequence of the ovine GR which displayed over 80% identity with residues 143-453 in human GR and 163-472 in rat GR. Furthermore, the first zinc finger motif in these receptors was perfectly conserved among species. The relative abundance of GR mRNA was studied in hypothalami, anterior pituitary glands and adrenals in fetuses at days 60-70, 100-110, 125-130 and at term (approximately 145 days), and in newborn lambs. Total RNA extracts (20 micrograms) were analysed by Northern blot analysis. A single 5.6 kb transcript was detected in all three fetal tissues, and its relative abundance did not change significantly throughout gestation. However, in newborn lambs, levels of GR mRNA increased significantly in the hypothalamus and pituitary gland but decreased to undetectable levels in the adrenal. These tissue-specific changes in the relative abundance of GR mRNA did not correlate with alterations in GR content in fetal tissues, which suggests that the latter may reflect alterations in GR mRNA translation, subsequent modifications and/or GR turnover. In addition, the pattern of developmental changes in GR mRNA content of the adrenal differs from that of the hypothalamus and pituitary gland in neonatal lambs, and indicates that tissue-specific factors may influence GR gene expression in neonatal sheep. PMID- 1515022 TI - Arachidonic acid-induced insulin secretion from rat islets of Langerhans. AB - There is growing evidence that arachidonic acid (AA) and/or its metabolites may be involved in the control of insulin secretion. We have now investigated the effect of AA on insulin secretion from rat islets, and the possible involvement of protein kinase C (PKC) in this process. Exogenous AA stimulated insulin secretion from intact islets at a substimulatory concentration of glucose (2 mM), but did not further enhance glucose-induced (20mM) insulin secretion. AA-induced insulin secretion was temperature dependent. The secretory responses seen at 37 degrees C were totally abolished by reducing the incubation temperature to less than or equal to 34 degrees C. AA-induced insulin secretion was not dependent upon extracellular Ca2+ and was potentiated by omission of Ca2+ or bovine serum albumin from the media. PKC in rat islets can thus be stimulated by AA, but the stimulation of PKC is not required for AA-induced insulin secretion. PMID- 1515024 TI - Photoaffinity labelled rat androgen-binding protein and human sex hormone steroid binding protein bind specifically to rat germ cells. AB - A specific receptor with high affinity for rat androgen-binding protein (rABP) was identified in isolated adult rat germ cells and in the corresponding plasma membrane-enriched preparations. Binding was reversible and time-dependent, with maximum relative binding after 40 min at 4 degrees C; it was pH-dependent, with maximum binding at pH 6-8. Unlabelled rABP and human sex steroid-binding protein (hSBP), but not lactotransferrin, serotransferrin, asialofetuin, fetuin or bovine serum albumin, competed with labelled rABP for binding sites on isolated germ cells. Scatchard analysis revealed a single class of binding site with apparent dissociation constant (Kd) values of 0.78 +/- 0.04 nM and 0.97 +/- 0.05 nM in intact germ cells and plasma membrane preparations respectively. A Kd of 1.72 +/- 0.12 nM for hSBP showed that the receptor binding site was effective for both androgen-carrier molecules. Labelled rABP incubated with solubilized germ cell membrane fractions at pH 7 formed a complex excluded from Superose 6B mini-gels; this complex was not formed at pH 3. The receptor complex was also abolished in the presence of a 100-fold excess of either unlabelled rABP or unlabelled hSBP, or in the presence of 20 mM EDTA. These results suggest that the plasma membrane of rat germ cells contains a receptor which selectively binds rABP and hSBP. PMID- 1515023 TI - The function of conserved elements in the promoter of the mouse angiotensinogen gene. AB - The angiotensinogen gene encodes the precursor protein for the potent vasoconstrictor angiotensin II. Although the gene is expressed in several tissues, the liver is the major source of circulating protein. In previous in vivo studies we have found that a mini-gene containing 750 bp of 5'-flanking sequence is transcribed in a manner which largely parallels the expression of the endogenous gene. In this report, we characterized conserved elements in the promoter region, in order to determine their role in the transcription of the angiotensinogen gene. Constructs fused to the chloramphenicol acetyl transferase (CAT) reporter gene were transfected into hepatocarcinoma Hep G2 cells as well as into nonhepatic cell lines. We found that 5'-deletion mutant constructs, containing sequences from +25 to -90 bp and -321 to -750 bp, were each able to activate transcription. These constructs contain the TATA box and core promoter sequences, including an Sp1-binding site, and two glucocorticoid responsive elements respectively. In the non-hepatic cell lines, HeLa and Jeg-3, we found that the constructs were transcribed at a much lower rate when compared with the expression of a plasmid containing the Rous sarcoma virus long terminal repeat fused to the CAT gene. Constructs which included sequence 5' to -244 were oestrogen inducible. An element which is conserved between rodent and human angiotensinogen promoters is contained within a sequence which is oestrogen responsive, while another binds the liver-enriched transcriptional activator hepatocyte nuclear factor 1. However, the role of this transactivator in the transcription of angiotensinogen remains uncertain. PMID- 1515025 TI - Identification of nuclear tri-iodothyronine receptors in Sertoli cells from immature piglet testes. AB - The existence of nuclear tri-iodothyronine (T3) receptors in both Sertoli and Leydig cells isolated from immature piglet testes was investigated. The results demonstrated the presence of high-affinity (Kd = 1.09 +/- 0.25 nM), low-capacity (185 +/- 24 pg T3/mg DNA) binding sites for T3 in nuclei from freshly isolated Sertoli cells. No specific binding for T3 was observed in nuclei isolated from Leydig cells. The localization of specific T3 receptors, which might mediate the onset of thyroid hormone action, at Sertoli cell level confirms that these cells are a target for thyroid hormone and strongly sustain the role of the thyroid in the regulation of testicular functions during postnatal development. PMID- 1515026 TI - Regulation of transcription factor mRNA accumulation during 3T3-L1 preadipocyte differentiation by tumour necrosis factor-alpha. AB - 3T3-L1 preadipocytes differentiate into cells having the biochemical properties of adipocytes; tumour necrosis factor-alpha (TNF) attenuates this process. Inhibition of differentiation by this cytokine, thought to be mediated at the level of transcription, has been investigated by examining the accumulation of mRNA for six transcription factors and three diversely regulated genes during the first 24 h of the differentiation process. Upon induction of differentiation, a rapid and major accumulation of c-fos and jun-B mRNA, which returned to near basal levels within 4-6 h, was observed. In contrast, c-jun mRNA, although rapidly expressed at the induction of differentiation, remained at relatively constant levels throughout the time-course. Exposure of the cells to 5 nM TNF potentiated the accumulation of all three mRNAs but most significantly that of c jun (12-fold), which remained elevated for at least 24 h after treatment. In control differentiating cells, krox-20 and fos-B were expressed transiently from 30 min to 2 h, while fra-1 mRNA accumulated over an extended period of 1 to 8 h. Again, TNF enhanced the accumulation of these mRNAs. Accumulation of mRNA for C/EBP, a transcription factor proposed to control the expression of genes involved in the terminally differentiated state, was attenuated after exposure of the cells to TNF. Interleukin-6 (IL-6) mRNA was expressed briefly (30 min to 2 h) and again transiently (at 8 h after induction of differentiation). TNF treatment markedly enhanced accumulation of IL-6 message. We propose that an increased cellular content of one or more transcription factors or the suppression of C/EBP may be responsible for the attenuation of differentiation induced by exposure of the cells to TNF. PMID- 1515027 TI - Characterization and localization of mRNA encoding the salmon-type gonadotrophin releasing hormone precursor of the masu salmon. AB - Gonadotrophin-releasing hormone (GnRH) is considered to have an important role in the control of reproduction in salmonid fish, although we do not have any direct evidence. To clarify this problem by molecular techniques, we first determined the nucleotide sequence of the mRNA encoding the precursor of salmon-type GnRH (sGnRH) from the masu salmon, Oncorhynchus masou. The masu salmon sGnRH precursor was composed of a signal peptide, sGnRH and a GnRH-associated peptide (GAP) which was connected to sGnRH by a Gly-Lys-Arg sequence. The amino acid sequence of sGnRH and Gly-Lys-Arg were highly conserved when compared with the corresponding regions of African cichlid sGnRH and mammalian GnRH precursors. However, the GAP region was markedly divergent, with a 66% amino acid similarity to African cichlid GAP and an 8.3-15% similarity to mammalian GAPs. Northern blot analysis indicated the presence of a single mRNA species of about 600 bases in the olfactory bulb and telencephalon and in the diencephalon. The signal was more intense in the former regions. An in-situ hybridization study further revealed that sGnRH neurones were distributed in the olfactory nerve, the ventral part of the olfactory bulb, the ventral part of the telencephalon, the lateral preoptic area and the preoptic nucleus. The sGnRH neurones were thus longitudinally scattered between the olfactory nerve and the lateral preoptic area in the rostroventral part of brain. The intensity of the hybridization signals and the size of hybridization-positive somata were much greater in the olfactory nerve and the rostral olfactory bulb than in the other regions. Preoptic sGnRH neurones were scarcely detected in immature masu salmon, whereas they were more frequently observed in maturing animals. It is possible that the olfactory and the preoptic sGnRH neurones have different physiological roles in salmonid fish. PMID- 1515028 TI - Production and characterization of recombinant chicken insulin-like growth factor I from Escherichia coli. AB - Recombinant chicken insulin-like growth factor-I (cIGF-I) has been produced in Escherichia coli after first modifying a plasmid that coded for a human IGF-I (hIGF-I) fusion protein, in order to introduce codons for the eight amino acid substitutions. The cIGF-I fusion protein, deposited in bacterial inclusion bodies, was dissolved under reducing conditions, desalted, subjected to anion exchange chromatography to remove proteinases, refolded and partially purified by reverse-phase high-performance liquid chromatography. The fusion protein was cleaved with hydroxylamine after which cIGF-I was purified to homogeneity by three additional chromatographic steps. Recombinant cIGF-I was equipotent with hIGF-I in cell culture bioassays of protein synthesis and breakdown using rat L6 myoblasts and chick embryo fibroblasts. Binding of radiolabelled cIGF-I and hIGF I was also equivalent in the two cell lines, as was their binding in ligand blots of chicken, sheep and human plasma. The cross-reactivity of cIGF-I in a polyclonal hIGF-I radioimmunoassay was 60% of that observed with hIGF-I. The availability of recombinant cIGF-I will facilitate investigations into the role of IGF-I in chicken growth and development. PMID- 1515029 TI - Synthesis of bombyxin-IV, an insulin superfamily peptide from the silkworm, Bombyx mori, by stepwise and selective formation of three disulfide bridges. AB - We report the synthesis of bombyxin-IV, a disulfide-linked, heterodimeric, insulin superfamily peptide from the silkworm, Bombyx mori. The two chains (A- and B-chains) were synthesized separately by the solid-phase method using fluoren 9-ylmethoxycarbonyl (Fmoc) group as a protecting group for alpha-amino group. Three disulfide bonds were bridged step by step (A6-A11, A20-B22, and A7-B10) in a good yield. Synthetic bombyxin-IV was identical with natural one with regard to the retention time on a reversed-phase column and the molecular weight measured by mass spectrometry. Circular dichroism (CD) spectrum of the synthetic bombyxin IV was very similar to that of the natural one. The specific activity of synthetic bombyxin-IV is equal to that of natural one (0.1 ng/Samia unit). These results suggest that the synthetic bombyxin-IV has the tertiary structure identical with the natural peptide. Our method developed for synthesis of bombyxin-IV would be generally applicable to the synthesis of insulin-like heterodimeric peptides. PMID- 1515030 TI - Determination of disulfide bond arrangement in bombyxin-IV, an insulin superfamily peptide from the silkworm, Bombyx mori, by combination of thermolysin digestion of natural peptide and selective synthesis of disulfide bond isomers. AB - The mode of disulfide linkages in bombyxin-IV, an insulin superfamily peptide consisting of A- and B-chains, was determined as A6-A11, A7-B10, and A20-B22. An intermolecular bond of A20-B22 was identified by sequencing and mass spectrometric analysis of the fragments generated by thermolysin digestion of natural bombyxin-IV. The mode of the remaining two bridges was determined by chemical and selective synthesis of three possible disulfide bond isomers of bombyxin-IV. A- and B-chains were synthesized by solid-phase method, and three disulfide bonds were bridged stepwise and in a fully controlled manner. Retention time on reversed-phase high-performance liquid chromatography (HPLC), thermolysin digests, and biological activity of the synthetic [A6-A11, A7-B10, A20-B22 cystine]-bombyxin-IV revealed that it was identical with the natural bombyxin-IV. Two other isomers with respect to disulfide bond arrangement, [A6-A7, A11-B10, A20-B22-cystine]- and [A6-B10, A7-A11, A20-B22-cystine]-bombyxin-IVs, were distinguishable from the natural one by use of HPLC, thermolysin digestion, and bioassay. PMID- 1515031 TI - Reexamination of the polymeric distributions of kappa-casein isolated from bovine milk. AB - kappa-Casein the stabilizing protein of the colloidal milk protein complex was purified from bovine skim milk by the method of McKenzie and Wake (Biochim, Biophys. Acta. 47, 240, 1961). The preparations were examined by sodium dodecyl sulfate gel electrophoresis in the presence and absence of a reducing agent. In the presence of a reducing agent, the kappa-casein migrates as a single low molecular weight band. However, in the absence of a reducing agent, a characteristic pattern of aggregates of varying molecular weight was observed with components ranging from monomer to octamer in integer steps. Densitometry of the Coomassie blue stained gels showed an almost equal distribution of components in each band; carbohydrate staining showed preferential location of sugar residues in lower molecular weight components. Treatment with chymosin (rennin) caused a downward shift in apparent molecular weight for each band with no change in the relative intensity of the Coomassie blue stained bands. Similar gel patterns were observed in whole caseins and partially purified kappa-caseins, indicating that this size distribution is a natural disulfide-linked reporter for the distribution of kappa-casein in casein colloids (micelles). PMID- 1515032 TI - Amino acid sequence of the coelomic C globin from the sea cucumber Caudina (Molpadia) arenicola. AB - The sequence of a globin from a marine invertebrate, the sea cucumber Caudina (Molpadia) arenicola (Echinodermata), is reported. This globin, chain C, is one of four major globins found in coelomic red cells in this organism and is the second to be sequenced. Chain C consists of 157 residues, is amino-terminally acetylated, and has an extended amino-terminal region. This globin shares a 60% sequence identity with the other sequenced C. arenicola globin, D chain (Mauri et al., Biochem. Biophys. Acta 1078, 63-67, 1991), but has a 93.6% identity with a globin from another sea cucumber, Paracaudina chilensis (Suzuki, Biochem. Biophys. Acta, 998, 292-296, 1989). PMID- 1515033 TI - Carnivora: the primary structure of the major hemoglobin component from adult European lynx (Lynx lynx, Felidae). AB - The complete primary structure of the major hemoglobin component from the adult European lynx (Lynx lynx) is presented. Presence of two hemoglobin components and three chains, beta A, beta B, and alpha, identified by gel electrophoresis. The purification of the globin chains achieved by ion-exchange chromatography. The globin chains were digested with trypsin. The peptide generated were purified by reversed-phase HPLC. Sequencing of the native chains up to 42 cycles and of the tryptic peptides were deduced by Edman degradation in liquid- and gas-phase sequencer. The primary structure established aligned with those of human Hb-A. The comparison of lynx globin chains with other representatives of the Felidae, lion, tiger, jaguar, leopard, and cat revealed high homology. PMID- 1515034 TI - Specific peptide-bond cleavage by microwave irradiation in weak acid solution. AB - A rapid and selective peptide-bond cleavage in weak acid, induced by microwave irradiation, has been developed. The specific cleavage sites of peptide bonds located only at the carboxyl- and amino-terminal ends of aspartyl residues along the peptide chain. A systematic study including the time course for the cleavage of various aspartyl-containing peptides, the effect of the acidity of the reaction solution on the completeness of peptide-bond cleavage, and the relationship between the power of microwave irradiation and the reaction time of cleavage are studied. PMID- 1515035 TI - Proteolytic digestion of alpha-lactalbumin: physiological implications. AB - The kinetics of the partial digestion of bovine alpha-lactalbumin (alpha-LA) by trypsin, alpha-chymotrypsin, and pepsin was monitored by lactose synthase activity, HPLC, and difference spectrophotometry. The relative stabilities of the various metal-bound states of alpha-LA to trypsin and chymotrypsin at 37 and 5 degrees C decrease in the following order: Ca(II)-alpha-LA greater than Zn(II), Ca(II)-alpha-LA greater than apo-alpha-LA. The HPLC digestion patterns of Ca(II) alpha-LA and Zn(II), Ca(II)-alpha-LA at 5 and 37 degrees C were similar, while the corresponding digestion patterns for apo-alpha-LA were quite different, reflecting the existence of the thermally induced denaturation states of apo alpha-LA within this temperature region. Occupation of the first Zn(II)-binding site in Ca(II)-loaded alpha-LA slightly alters the HPLC digestion patterns at both temperatures and accelerates the digestion at 37 degrees C due to Zn(II) induced shift of the thermal transition of alpha-LA, exposing some portion of thermally denatured protein. The results suggest that the binding of Zn(II) to the first Zn(II)- (or Cu(II)-specific site does not cause any drastic changes in the overall structure of alpha-LA. The acidic form of alpha-LA (at pH 2.2 and 37 degrees C) was digested by pepsin at rates similar to that for the apo- or Cu(II), Ca(II)-loaded forms by trypsin or alpha-chymotrypsin at neutral pH. Complexation of alpha-LA with bis-ANS affords protection against pepsin cleavage. It is suggested that the protective effects of similar small lipophilic compounds to alpha-LA may have physiological significance (e.g., for nutritional transport). PMID- 1515037 TI - Perspectives on toxicological risk--an example: foodborne carcinogenic risk. AB - Epidemiologists estimate that approximately one third of all cancer deaths can be attributed to diet. It is instructive to attempt to apportion this dietary carcinogenic risk to the specific classes of foodstuffs and food additives, pesticides, etc., that are typically regulated. When this is done it is evident that virtually all the calculated risk can be attributed to naturally occurring carcinogens in the diet. This article indicates that both epidemiological data and the simplest kind of risk assessment agree that foodborne carcinogenic risk probably overwhelmingly originates from the food itself and not from additives, pesticides, or contaminants. PMID- 1515036 TI - Modification of aldehyde dehydrogenase with dicyclohexylcarbodiimide: separation of dehydrogenase from esterase activity. AB - Dehydrogenase activity of the cytoplasmic (E1) isozyme of human liver aldehyde dehydrogenase (EC 1.2.1.3) was almost totally abolished (3% activity remaining) by preincubation with dicyclohexylcarbodiimide (DCC), while esterase activity with p-nitrophenyl acetate as substrate remained intact. The esterase reaction of the modified enzyme exhibited a hysteretic burst prior to achieving steady-state velocity; addition of NAD+ abolished the burst. The Km for p-nitrophenyl acetate was increased, but physicochemical properties remained unchanged. The selective inactivation of dehydrogenase activity was the result of covalent bond formation. Protection by NAD+ and chloral, saturation kinetics, and the stoichiometry and specificity of interaction indicated that the reaction of DCC occurred at the active site of the E1 isozyme. The results suggested the some amino acid other than aspartate or glutamate, possibly a cysteine residue, located on a large tryptic peptide of the E1 enzyme, may have reacted with DCC. PMID- 1515038 TI - Issues associated with the use and regulation of fat substitutes. PMID- 1515039 TI - The safety evaluation of macronutrient substitutes. PMID- 1515040 TI - Safety evaluation of olestra, a nonabsorbed, fatlike fat replacement. AB - Olestra is the mixture of the hexa-, hepta-, and octa-esters of sucrose with long chain fatty acids from any edible oil. Its physical properties are comparable to those of triglycerides, but it is not digested by lipolytic enzymes or absorbed and therefore is noncaloric. Technically, it can replace fat in a wide variety of foods and can be used to make cooked, baked, and fried foods lower in fat and calories. A Food Additive Petition is under review by the FDA, which is comprised of results of extensive testing in animals and humans. The major areas of investigation are metabolism and absorption, chronic toxicity, mutagenicity, carcinogenicity, reproductive and developmental toxicity, safety for gastrointestinal tract, nutrition, and the potential for olestra to affect absorption of drugs. This testing involved studies in five different species of animals and over 30 clinical investigations. The results of this research support the safety of olestra for use in foods. PMID- 1515041 TI - Biotechnology-derived foods from animals. AB - American agriculture is being challenged to produce food in a way that is environmentally sound, that enhances human health, is safe, and whose cost is competitive internationally. The tools of biotechnology offer new techniques for modifying biological traits in a much more directed way than is possible with conventional animal breeding and enables us to ask questions and find answers in a way that was not possible in the past. The new tools facilitate disease diagnosis and prevention, help design foods with improved nutritional characteristics, and increase production efficiency. Full realization of the potential of biotechnology will depend upon our ability to deal with public perceptions of "genetic engineering", support for research, and policy issues such as patenting of animals. PMID- 1515042 TI - Status of regulatory approval of biotechnology-derived plants and animals. AB - Development of new technology brings with it decisions regarding regulation to ensure safety in technology transfer. Properly formulated and administrated, such regulations can act as a catalyst for the transfer of new technology, not a barrier. Such regulations must be based on sound scientific principles, and are intended to provide protection for the public, engender public acceptance, and foster communication with the various segments of society. To develop this new technology in a safe and orderly manner field testing of the products/organisms of biotechnology, especially genetic engineering, has been permitted by the U.S. Department of Agriculture (USDA). USDA permits certify the environmental safety of field testing of plants and microorganisms developed through the use of material derived from plant pests. Permits are issued based upon analyses of the biology of the organism, the affected environment, and the precautions taken to ensure environmental protection. Licenses for the use of veterinary biologics, including recombinant vaccines, are also issued. PMID- 1515043 TI - A new approach for assessing the dietary exposure to food additives. AB - By analyzing composite samples of brand name foods, a new method called the Dietary Exposure Assessment Method (DEAM), if found to be feasible, may provide useful estimates of daily intake of food additives for major portions of the U.S. population. PMID- 1515044 TI - Overview of FDA's Redbook guidelines. AB - As part of its responsibility, the Food and Drug Administration provides guidance to industry and the public concerning the procedures and methods for safety assessment of food and color additives. The FDA published its guidelines in 1982 as the so-called "Redbook" ("Toxicological Principles for the Safety Assessment of Direct Food Additives and Color Additives Used in Food"). The Center for Food Safety and Applied Nutrition of the FDA is now in the process of revising and updating the Redbook in light of developments in toxicological testing methods and comments from the scientific community and the public. The effort involves a number of center scientists who have special expertise in various areas of toxicology and food safety assessment. The goal is to make the revised Redbook more useful and practical and to address areas of safety assessment not covered in the 1982 edition. The several papers that follow deal with chapters that will be new to the Redbook. PMID- 1515045 TI - Revisions to the FDA's Redbook guidelines for toxicity testing: neurotoxicity. AB - In 1982, the Food and Drug Administration issued a publication, known as the Redbook, that described the current toxicological principles used for the safety assessment of regulated food and color additives. However, this document contained only minimum reference to neurotoxicity as a specific toxicological concern and only general mention of the types of data that should be collected to detect and assess adverse changes to the nervous system. The general nature of the toxicological information typically derived from studies based on the original Redbook has had only limited use as a guide for comprehensive assessment of neurotoxic hazard. This limitation is one of the issues being addressed in the current efforts to update the information provided in the Redbook. In the revised Redbook, neurotoxicity, encompassing adverse structural and functional changes to the nervous system, is explicitly identified as an important criterion in the assessment of food chemical safety. The proposed strategy for evaluating neurotoxic hazard has a tiered testing approach. Accordingly, testing would initially involve the identification of chemicals presumptively associated with neurotoxic effects. As appropriate, subsequent testing would be carried out to confirm and delineate the scope of the neurotoxicity, to determine the dose response kinetics, and to define the no-adverse-effect levels. PMID- 1515046 TI - Testing guidelines for evaluation of the immunotoxic potential of direct food additives. AB - Immunotoxicity testing is a new addition to the safety assessment guidelines for direct food and color additives. The approaches and philosophy for this area of specialized testing are consistent with the case-by-case strategy applied in the regulatory approval process, which is based on structure-activity relationships, preexisting knowledge, and projected exposure estimates. Specialized testing such as immunotoxicity is not part of the basic testing requirements, but would be applied when indicators are positive. Concepts for immunotoxicity testing have evolved, in part, from research for evaluating various testing methods as well as specific study designs. This research, conducted over the last decade, has focused mainly on the rat as the rodent species of choice. The miniature swine was evaluated as a nonrodent model. Testing is defined by type 1 and type 2 tests, which differ in that type 1 tests are performed on the same animals used in the core study design. Sets of type 1 and type 2 tests, with reference to the indicators, define various testing levels. Retrospective testing, expansion of basic testing (such as histopathology and serum chemistry profiles), and alternative study designs, which include satellite groups for evaluation of the functional capacity of the immune system, can be considered in the evaluation of immunotoxic potential. PMID- 1515047 TI - Evaluating the safety of food and color additives with pharmacokinetic data. AB - Pharmacokinetic studies are designed to quantify, as a function of time, the processes associated with absorption, distribution, metabolism, and excretion of a chemical in experimental animals or in humans. Such studies have played an important role in drug safety evaluation and could be very useful in the safety evaluation of food and color additives. This presentation provides an overview of the potential use of metabolic and pharmacokinetic data in the design and evaluation of toxicological studies and in the assessment of the potential hazard to humans from exposure to food or color additives. PMID- 1515048 TI - Improvement of oral bioavailability of fenbufen by cyclodextrin complexations. AB - The interactions of fenbufen (FB) with alpha-, beta-, gamma-cyclodextrins (CyDs) were studied in aqueous solution and in solid state. beta-CyD formed water soluble complex with FB in the molar ratio of 1:2 (guest:host). The solid complex of FB with alpha-CyD was obtained in the molar ratio of 1:2 (guest:host), while the same with gamma-CyD was obtained as 1:1 ratio. The dissolution rate and bioavailability of FB were significantly increased by the formation of inclusion complexes (alpha greater than gamma-CyD complex). CyDs had no effect on the metabolic time of FB forming two active metabolites, and the bioavailability of metabolites was also increased by complexation of FB with CyDs. The bitter taste of FB powder was reduced by alpha-CyD complexation. The enhanced bioavailability and reduced bitterness of FB by CyD complexations suggested the possibility of applying FB in smaller doses with fewer side-effects. PMID- 1515049 TI - Increase in thebaine content of Papaver bracteatum Lindl. after colchicine treatment of seeds. Annual fluctuations in thebaine level of individual plants. AB - From colchicine-treated seeds of Papaver bracteatum Lindl. some poppy plants were obtained that developed capsules richer in thebaine than the controls. The individual poppies were analyzed for capsule thebaine content annually for eight successive years, the results revealing significant year-to-year differences. One of the poppies, X7, (ca 5% thebaine) developed capsules consisting partly of polyploid tissue during the first and second year. This plant was propagated vegetatively to give a series (the X7 series) of new P. bracteatum plants. The capsule thebaine content of these individuals differed markedly the first two years, whereupon the alkaloid production decreased and appeared to level out and reach a value still clearly higher than the controls (mean values 2.3% and 1.3%, respectively). From seeds of four of the thebaine-rich poppies of the X7 series, four new series of P. bracteatum plants were obtained. The capsule thebaine level of these was significantly lower than that of the mother plants. PMID- 1515050 TI - N-substituted (aminomethyl)benzoate 21-esters of corticosteroids as water soluble, solution-stable and biolabile prodrugs. AB - Various N-substituted 3- or 4-(aminomethyl)benzoate 21-esters of hydrocortisone, prednisolone and methylprednisolone were synthesized and evaluated as water soluble prodrug forms, with the aim of developing improved preparations for parenteral or ophthalmic administration. All esters were readily hydrolyzed enzymatically by human plasma. The half lives of hydrolysis in 80% plasma ranged from 8 min to 342 min, the rate being dependent on the structure of the amino group and its position relative to the ester moiety, as well as on the structure of the steroid. The esters showed maximal stability in aqueous solution at pH 3 4. From temperature-accelerated studies of the 3-[(4-methylpiperazin-1 yl)methyl)]benzoate ester of hydrocortisone, the shelf life of an aqueous solution (pH 4.0) of this ester was predicted to be 6 years at 25 degrees C. This estimated shelf life is not reduced by precipitation of the slightly soluble parent drug since the ester was shown to be capable of solubilizing hydrocortisone, possibly by self-micelization. PMID- 1515051 TI - Prodrugs of thiabendazole with increased water-solubility. AB - The poor peroral absorption of benzimidazole anthelmintics limits their usefulness for the treatment of systemic infections such as alveolar or cystic echinococcosis. The low bioavailability has mainly been attributed to the low aqueous solubility of the benzimidazoles. Using thiabendazole as a model compound the prodrug approach was investigated as a mean to obtain derivatives with improved water-solubilities. Bioreversible derivatization of thiabendazole was performed by N-acylation of the benzimidazole moiety with various chloroformates as well as by N-acyloxymethylation. Both the N-alkoxycarbonyl and the N acyloxymethyl derivatives were readily hydrolyzed to thiabendazole in human plasma and in rat and pig liver homogenates. The pH-rate profiles for the hydrolysis of the derivatives were determined and the lipophilicity of the compounds was assessed by partition experiments. The water-solubility of the N alkoxycarbonyl derivatives was up to 12 times higher than that of the parent drug. An N-(4-amino-methylbenzoyl)oxymethyl derivative possessed a 300-fold higher water-solubility. The improved aqueous solubility, adequate lipophilicity and chemical stability combined with a facile enzymatic hydrolysis make such derivatives promising prodrugs for benzimidazole anthelmintics with the aim of improving the peroral bioavailability. PMID- 1515052 TI - Effect of particle size on ocular permeability of prednisolone acetate in rabbits. AB - The ocular permeability of two sieved fractions of prednisolone acetate with a mean particle size of less than 5 microns and 5-10 microns was studied in rabbits. The results show that there was not significant difference between the corneal uptake of the two fractions of prednisolone acetate. Prednisolone acetate was rapidly taken up by the cornea where it is hydrolyzed rapidly to prednisolone. Only prednisolone was detected in the aqueous humor showing that prednisolone acetate is completely hydrolyzed in the cornea. Both fractions produced similar concentrations of prednisolone in the aqueous humor. For prednisolone acetate, the permeability rate rather than the dissolution rate seems to be the rate-limiting step for corneal transport. PMID- 1515053 TI - Effect of terminal heat sterilization on the stability of phospholipid-stabilized submicron emulsions. AB - Parenteral emulsions similar in composition to the commercially available fat emulsions were prepared using a Microfluidizer. The relationship of pH and terminal heat sterilization by autoclaving on the stability of phospholipid stabilized emulsions was evaluated. The stability of these formulations was determined by using droplet size and zeta potential measurements. It was found that the zeta potentials of emulsions stabilized by more purified phospholipid were lower in magnitude compared to those stabilized by less purified phospholipid. Furthermore, acidic emulsions (between pH 5.0 and 7.0) showed an increased droplet size upon autoclaving, whereas the emulsions adjusted to an alkaline pH (pH 8.0 to 10.0) did not show a significant change in their droplet sizes upon autoclaving. The zeta potentials of all the emulsions "increased" (in magnitude) upon autoclaving and achieved values between -40 and -50 mV. The results of our studies could be explained on the basis of hydrolysis of phosphatidylcholine at different pH values, leading to a breakdown of the film surrounding the oil droplet, which results in coalescence and/or cracking of the emulsions. PMID- 1515054 TI - The alkaloids of the roots of Thalictrum flavum L. AB - The main alkaloid in the roots of Thalictrum flavum is berberine. The alkaloids glaucine, thalicsimidine, thaliglucine, thalidazine, hernandezine and thalfoetidine were also isolated. PMID- 1515055 TI - Role of temperature and moisture, on monomer content of freeze-dried human albumin. PMID- 1515056 TI - Optimization of a matrix tablet formulation using a mixture design. AB - The simplex centroid design was applied to the optimization of a modified release tablet formulation. A base granulation was made with the active ingredient naftidrofuryl. The variables investigated included fractions of the excipients microcrystalline cellulose, lactose and dicalcium phosphate dihydrate. The release rate, crushing strength, friability and weight variation were determined as response parameters. Mathematical models were fitted to the data obtained by the lattice method, described by Scheffe and by means of multiple linear regression. Regression analysis indicated a relatively good fit of the models. On the basis of the regression models, contour plots were constructed. An increase in the amount of dicalcium phosphate caused lower release rate and increased weight variation. An increase in the content of lactose showed lower strength and increased friability, whereas an increase in the amount of microcrystalline cellulose had the opposite effect. PMID- 1515057 TI - Preparation, purification and characterization of chlorohaemin. AB - Preparation of chlorohaemin (CAS 16009-13-5) is performed on the basis of the method of Labbe and Nishida (acetone-acetic acid-SrCl2 method) with some significant modifications. Instead of blood as starting material, a fresh preparation of purified human erythrocytes is used. This avoids any contamination with serum and erythrocyte proteins and lipids of the end product. Special care is taken to remove contaminating globin by introducing some specific purification steps during isolation and recrystallisation. The yield is in the range 65-75% of theory, and the purity of the product is better than 99.9% as shown by elemental analysis and specific tests on various compounds as possible contaminants which originate from the starting material such as lipids and proteins and/or from the different steps of preparation and purification during the procedure. The pure chlorohaemin which is the compound of choice as reference substance for the AHD method in haemoglobinometry is characterized by LSI mass spectrometry (m/z = 616, haemin ion), field desorption-mass spectrometry (m/z = 652), by IR-spectroscopy, and by UV/VIS absorption spectroscopy (pyridine haemochrome spectrum, AHD spectrum). PMID- 1515058 TI - Incorporation of the enantiomers of lipoic acid into the pyruvate dehydrogenase complex from Escherichia coli in vivo. AB - The uptake of 35S-labelled enantiomers of lipoic acid into cells from Escherichia coli was studied. The R-enantiomer was taken up by a factor of two more efficiently than the S-form. Autoradiography of polyacrylamide gels of partially purified pyruvate dehydrogenase complex from these cells showed that only the R lipoic acid was covalently incorporated as a cofactor into the dihydrolipoamide acetyltransferase component of the pyruvate dehydrogenase complex. PMID- 1515059 TI - Side chain distribution and enantiomer composition of biodegradable branched polypeptides with polylysine backbone. AB - A detailed investigation is reported about the primary structure of biodegradable branched polypeptides suitable for carrier function. The side chain distribution of poly[Lys(DL-Alam)], m approximately 3.5, the common inside area of a branched polypeptide model system, was determined by automated Edman degradation. These data indicate that 65% of the branches consist of 2-4 Ala residues and 25% of the side chains are longer than 4 amino-acid residues. The enantiomer composition of poly[Lys(Xi-DL-Alam)], (X = Glu, D-Glu, Leu, D-Leu) and of poly[Lys(DL-Ala2.9 Leu0.79)] polypeptides was investigated by HPLC analysis of their hydrolysates following derivatization with N-(5-fluoro-2,4-dinitrophenyl)-L-alanine amide (Marfey's reagent). The results proved that the synthesis methods applied for the preparation of branched polypeptides produce compounds whose enantiomer compositions are in good agreement with calculated expectations. These findings could be useful for the reliable interpretation of various biological phenomena observed in connection with the presence of L- or D-amino-acid residues in the side chains. PMID- 1515060 TI - Microbial metabolism of quinoline and related compounds. XIV. Purification and properties of 1H-3-hydroxy-4-oxoquinoline oxygenase, a new extradiol cleavage enzyme from Pseudomonas putida strain 33/1. AB - 1H-3-Hydroxy-4-oxoquinoline oxygenase was purified to apparent homogeneity from Pseudomonas putida strain 33/1 which can use 1H-4-oxoquinoline as sole source of carbon. The molecular mass of the enzyme was determined to 26,000 Da by gel chromatography and by SDS polyacrylamide gel electrophoresis. The enzyme is labile at temperatures above 30 degrees C and has a pH optimum of 8.0. It requires oxygen for the reaction and is significantly inhibited by metal ions like Cu2+, Zn2+, Hg2+ and by 4-chloromercuribenzoate. The enzyme is specific only for 1H-3-Hydroxy-4-oxoquinoline; the apparent Km value for this substrate is 24 microM. PMID- 1515061 TI - Oligopeptidases, and the emergence of the prolyl oligopeptidase family. AB - Oligopeptidases are endopeptidases that are not proteinases in the strict sense, since they do not hydrolyse peptide bonds in proteins, but act only on smaller polypeptides or oligopeptides. These enzymes apparently perform important, specialized biological functions that include the modification or destruction of peptide messenger molecules. Oligopeptidases have few naturally occurring inhibitors, and their distinctive specificity prevents them from interacting with alpha 2-macroglobulin, unlike the great majority of endopeptidases. The specificity of these specialized endopeptidases doubtless depends upon the three dimensional structure of the active site, but no crystallographic structure is yet available for an oligopeptidase. Study of the primary structure of prolyl oligopeptidase has recently shown that it is a member of a new family of serine type peptidases most of which are exopeptidases. The alignment of the sequences leads to the identification of some catalytic triad residues that have not yet been elucidated experimentally. PMID- 1515062 TI - The primary structure and tissue distribution of cathepsin C. AB - A cDNA for rat cathepsin C (dipeptidylaminopeptidase I) was isolated. The encoded protein is composed of the signal peptide of 28 residues, the propeptide of 201 residues and the mature enzyme region of 233 residues. The amino acid sequence of the mature enzyme region has 39.5 to 30.5% identity to other papain family proteinases. Cathepsin C is, therefore, belongs to papain family, although its propeptide region is much longer than those of other cysteine proteinases and show no significant sequence similarity to any other cysteine proteinase. The mRNA and protein for cathepsin C are broadly distributed in rat tissues, but the relative proportions of cathepsin C and other cysteine proteinases are found to vary from tissue to tissue. PMID- 1515063 TI - Basic amino acids preferring broad specificity aminopeptidase from human erythrocytes. AB - An aminopeptidase hydrolyzing 2-naphthylamides of Lys, Arg, Leu, Met, Phe and Tyr, as well as different di- to tridecapeptides, was purified from the cytosol of human erythrocytes. The enzyme showed preference for Lys and Arg at N terminus, as proline and D-amino acids were nonpermissive at P1' site. Higher affinity for oligopeptides than for aminoacyl naphthylamides was observed. Among the substrates were Lys-bradykinin, angiotensin III, thymopentin and enkephalins. Aminopeptidase was shown to be a monomeric protein of M(r) approximately 110000 and of pI approximately 4.8, activated by Co2+ and inhibited by EDTA, pHMB, amastatin, bestatin and puromycin. The isolated enzyme could be classified as cytosolic, Lys(Arg) preferring, broad specificity aminopeptidase. PMID- 1515064 TI - A new family of proteinases is defined by several snake venom metalloproteinases. AB - Recently, the complete amino acid sequences have been determined for several snake venom metalloproteinases from the genera Crotalus, Trimeresurus and Lachesis of the Crotalidae family. Among these are both hemorrhagic and nonhemorrhagic metalloproteinases. Despite differences in their molecular weights and activities, they all appear to be related through a single ancestral gene, as observed by the comparison of their amino acid sequences. None of these proteins bear significant similarity to any other known protein, with the exception of the zinc binding site demonstrated in thermolysin and other metalloproteinases. Thus we propose that these proteins define a new family of zinc metalloproteinases which is likely to consist of (but is not necessarily limited to) many of the zinc metalloproteinases found in snake venoms. PMID- 1515065 TI - Pancreatic procarboxypeptidases: their activation processes related to the structural features of the zymogens and activation segments. AB - The molecular events leading to the complete activation of pancreatic procarboxypeptidases A and B have been investigated. For both proteins the activation process follows a similar general scheme: trypsin is responsible for the first cleavage that separates the active enzyme from the activation segment, the degradation of the activation segment proceeds only from its C-terminal end, and activity release can be correlated with the disappearance of the long forms of the activation segment. In both systems, trypsin and the released carboxypeptidase participate in the trimming of the severed activation regions. However, the rate of enzymatic activation is much faster in the case of procarboxypeptidase B. This phenomenon may be explained by some structural differences in the connecting region which acts as a linker between the globular domain of the activation segment and the N-terminal end of carboxypeptidases and also by the higher efficiency of carboxypeptidase B for the digestion of its own activation segment. It is not due to unfolding of the activation domain, since the isolated activation domain retains its globular conformation in solution. PMID- 1515066 TI - The characteristics of cysteine proteinases of parasitic protozoa. AB - Cysteine proteinases have now been detected in most of the important species of parasitic protozoa. Characterization of the enzymes and sequence determinations have revealed that the enzymes are related to papain and the mammalian cathepsins. All of the protozoan enzymes analyzed to date are members of the cathepsin L/cathepsin H/papain branch of the papain superfamily and are more distantly related to cathepsin B. They thus share some characteristics with the cysteine proteinases of their hosts. Individual enzymes, however, are likely to have sufficient novel features to be potential targets for specific antiprotozoal drugs, and a number of proteinase inhibitors and substrates are currently being tested as possible chemotherapeutic agents. PMID- 1515067 TI - Bovine cathepsins S and L: isolation and amino acid sequences. AB - The purification procedure of cathepsin S includes acid activation of spleen homogenate, incubation at 37 degrees C, precipitation with (NH4)2SO4 in H2O/tert butanol medium, gel chromatography, chromatofocusing, covalent chromatography and cation chromatography of FPLC system. Cathepsin S has a M(r) of about 24,000 Da with pI of 6.5 and 6.8. The mixture of both forms gave a single sequence. Cathepsin L was purified from bovine kidney by acid treatment and incubation of 37 degrees C, precipitation by (NH4)2SO4, two ion exchange chromatographies on CM Sephadex, gel chromatography and ion exchange chromatography on FPLC system. Cathepsin L exists in multiple forms with pI 5.3-5.7 and M(r) of about 29,000 Da. N-terminal amino acid sequence confirms that cathepsin L and cathepsin S are different enzymes. PMID- 1515068 TI - Investigation of structure function relationships in cathepsin B. AB - Previous suggestions from sequence alignment studies and examination of the recently determined X-ray crystal structures of cathepsin B point to roles for several specific residues in substrate binding and catalysis. The role of these groups is being examined by studying cathepsin B mutants produced using a yeast expression system. The substitutions Gly198Asp, Arg202Ala, His111Gln and Glu245Gln provide a mechanistic basis for the exopeptidase activity of cathepsin B and the ability of this cysteine proteinase to accept an arginine residue in the S2 subsite. PMID- 1515069 TI - Characterisation of the activity and stability of single-chain cathepsin L and of proteolytically active cathepsin L/cystatin complexes. AB - The activity of single-chain cathepsin L was found to be markedly dependent on cysteine concentration, while a covalent, proteolytically active cathepsin L/cystatin complex was less cysteine-dependent. Cysteine levels and ionic strength did not affect the stability of either enzyme form and both enzyme forms were found to be stable for significant periods of time at or near physiological pH. PMID- 1515070 TI - Antibodies to rat procathepsin B recognize the active mature enzyme. AB - Use of mature cathepsin B for immunization invariably yields antisera that react with the denatured protein but not with the native enzyme. This is thought to be due to spontaneous denaturation of the immunizing antigen on introduction into the animal. Recombinant rat procathepsin B has been expressed in yeast as a secreted product. A procathepsin B mutant (Cys29Ser), where autoprocessing is prevented, has been purified and used to raise a rabbit polyclonal antiserum. Both immunodiffusion analysis and an activity depletion assay demonstrated that this antibody recognized native mature cathepsin B. It appears that conformational epitopes existing on the active enzyme are lost on denaturation. The stability of the proenzyme however permits their presentation for antibody generation. PMID- 1515071 TI - Membrane permeable fluorogenic rhodamine substrates for selective determination of cathepsin L. AB - The dipeptidyl rhodamine diamide substrates (Z-Phe-Arg)2-R110 and (Z-Arg-Arg)2 R110 are 820- and 360-fold more selective for cathepsin L than for cathepsin B allowing a sensitive determination of cathepsin L activity in the presence of high activity of cathepsin B. The results obtained with cell lysates suggest that the cysteine proteinase activity of vital macrophages detected by flow cytometry with these substrates is mainly due to cathepsin L. PMID- 1515072 TI - Isolation and characterization of bovine stefin B. AB - A new cysteine proteinase inhibitor (CPI) was isolated from bovine thymus. According to the amino acid sequence it belongs to the stefin family. It appears as a monomer and a dimer with monomer M(r) of 11,178 and pI values 5.6 for the monomer and 5.2 and 5.6 for the dimer. Ki for the interaction with papain was determined to be 0.12 nM. The most interesting feature of bovine stefin B is the replacement of the highly conserved QVVAG region in stefins with the QLVAG sequence without interfering its inhibitory properties. PMID- 1515073 TI - Conformation and fluctuations of free stefin B: a molecular dynamics study. AB - Molecular dynamics study was performed on the cysteine proteinase inhibitor stefin B. Structure of inhibitor from the complex with papain was used as a starting point. Amino terminal "trunk" of the inhibitor which lies extended along the cleft of the enzyme in the complex, folded onto the body of inhibitor during MD simulation, thereby reducing the total and particularly hydrophobic surface exposed to the solvent. This effect counterbalances hydrophobic contribution of the "trunk" and explains why its deletion in stefin B and related inhibitors doesn't reduce the dissociation constant. The rest of stefin B conformation is conserved together with main chain hydrogen bonds. Fluctuations of C alpha atoms resembles crystallographic B factors with exception of residues in contact with enzyme. PMID- 1515074 TI - Denaturation of stefin B by GuHCl, pH and heat; evidence for molten globule intermediates. AB - GuHCl, pH and thermal denaturation of the recombinant stefin B was followed by circular dichroism (CD) and size-exclusion chromatography (SEC). CD at 277 nm was taken as an indicator of integral tertiary structure and CD at 222 nm as an indicator of the secondary structure. Compactness was expressed by the volumes of elution on a SEC (Superose 12) column. Data on equilibrium denaturation were recalculated to the fractions of the native state (fN). The results have shown that equilibrium intermediates of the molten globule type exist under conditions of low pH, high temperature or medium GuHCl concentrations, namely A, T and G. Recent findings on structure and energetics of molten globule intermediates are reviewed. PMID- 1515075 TI - Characterization and structure of pineapple stem inhibitor of cysteine proteinases. AB - The complete amino acid sequence of the inhibitor of cysteine proteinases from pineapple stem acetone powder was determined. The inhibitor consists of 52 amino acids and is composed of two polypeptide chains (41 and 11 amino acids) linked via disulphide bonds. It differs from already known sequences in one to four amino acids. Data from its amino acid sequence analysis clearly show that this inhibitor cannot be a member of the cystatin superfamily. The Ki values for papain, bromelain and cathepsin L were determined. PMID- 1515076 TI - Cystatin mimicry by synthetic peptides. AB - Synthetic peptides which tentatively mimic the cystatin inhibitory surface were used to study the mechanism of inhibition of cysteine proteinases by their natural inhibitors. The inhibitory properties of these peptides depend mainly on the presence of the QxVxG consensus sequence. N and C-terminal peptide derivatives bearing large hydrophobic groups showed dramatically improved inhibition. Molecular dynamic studies after energy minimization showed that the non covalent interaction between these hydrophobic groups induced the formation of a loop structure which probably favours inhibition. Antibodies were raised against one of these peptides, which recognized kininogens in the serum of all mammal species tested, but not cystatins from family two. PMID- 1515077 TI - Demonstration of sequence variations in the promoter region of the human cystatin C gene. AB - Four point mutations in the promoter region of the human cystatin C gene have been detected by direct sequencing of polymerase chain reaction (PCR) amplified DNA. The four base changes are all localized within a short segment of 85 base pairs. Three cystatin C gene alleles could be defined with respect to these promoter mutations; one with the sequence previously published, one carrying three of the mutations and one with all four base substitutions. Two of the observed mutations are involved in a novel Sst II polymorphism and another generates a new Dde I restriction site. A PCR-based assay for analysis of these Sst II and Dde I sites was designed and used to demonstrate Mendelian inheritance of the polymorphisms as well as to determine the frequencies of the cystatin C gene alleles in the population. PMID- 1515078 TI - Characterization of aspartic proteinase inhibitors from potato at the gene, cDNA and protein levels. PMID- 1515079 TI - Bovine tryptase: purification and characterization. AB - Bovine tryptase, a mast cell trypsin-like protease, was isolated from liver capsula and from mast cells obtained from the same tissue. The purification procedure which leads to an increase in tryptase activity of 850 fold, involves high salt extraction, hydrophobic interaction chromatography on octyl-Sepharose and affinity chromatography on heparin-Sepharose. The enzyme is oligomeric, with an apparent M(r) of 360,000 +/- 40,000 (as obtained by gel filtration in high salt). The constituent subunits with M(r) 39,000 and 41,000 Da are both labeled with [3H] diisopropyl fluorophosphate and cross-react with anti-rat tryptase immunoglobulins. Only a single N-terminal sequence was found, identical to that of human, dog and rat tryptases. Tripeptide fluorogenic substrates with basic residues in P1 and P2 positions are preferentially hydrolyzed by this enzyme, suggesting a possible processing role as proposed for other tryptases. Bovine tryptase activity is inhibited by NaCl and is insensitive to high molecular weight inhibitors, such as alpha 1 antitrypsin and soybean trypsin inhibitor, as for human and dog tryptases. However it is inhibited by low molecular weight serine protease inhibitors and, similarly to rat tryptase, by the bovine pancreatic trypsin inhibitor (BPTI or aprotinin), in a pH dependent fashion. PMID- 1515080 TI - Interactions of thrombin with benzamidine-based inhibitors. AB - Trypsin and trypsin-like enzymes cleave C-terminal bonds of the basic amino acids Arg and Lys. Inhibitors of these enzymes have been found not only among Arg and Lys derivatives but also with structurally related benzamidines. Especially cyclic amides of 4-amidinophenylalanine were found to be inhibitors of thrombin. The most potent selective thrombin inhibitor of these type is N alpha-(beta naphthylsulfonylglycyl)-4-amidinophenylalanine piperidine. From the X-ray crystal structures of thrombin and trypsin-inhibitor complexes the thrombin complexes formed with inhibitors derived from amidinophenylalanine have been modeled. These models allow valuable predictions to design inhibitors of improved selection and binding properties. Most recently, also the X-ray crystal structures of complexes of inhibitors with bovine thrombin have been solved. PMID- 1515081 TI - The biology and biochemistry of antichymotrypsin and its potential role as a therapeutic agent. PMID- 1515082 TI - Heparin interferes with the inhibition of neutrophil elastase by its physiological inhibitors. AB - Heparin depresses the second-order rate constant kass for the inhibition of neutrophil elastase by alpha 1-proteinase inhibitor. For high and low molecular weight heparin the decrease in kass is 290-fold and 40-fold, respectively. This is due to a tight binding of the polymer to elastase: Kd = 3.3 nM or 89 nM for high or low molecular weight heparin respectively. In contrast heparin increases the rate of inhibition of elastase by mucus proteinase inhibitor. For low molecular weight heparin, there is a 27-fold increase in kass. This is due to a strong binding of the polymer to the inhibitor (Kd = 50 nM) which undergoes a conformational change. PMID- 1515083 TI - Assay of HIV protease dimerization. PMID- 1515084 TI - Migration of polymorphonuclear leukocytes through human amnion membrane--a scanning electron microscopic study. AB - Scanning electron microscopy has been used to examine the changes in the basement membrane structure induced by polymorphonuclear leukocytes during leukodiapedesis. A diapedesis model based on a Boyden chamber fitted with a human amnion membrane simulated inflammatory processes during which leukocytes are stimulated to leave blood vessels and to penetrate basement membranes. In the Boyden chamber, a chemotactic gradient was developed from a solution of 10(-7) M formyl-methionyl-leucyl-phenylalanine, which induced the cells to migrate through the membrane. Our observations suggest that leukocytes, like tumor cells, emigrate in a three-step process. In the first instance, they adhere to the basement membrane. A local partial proteolysis follows, which is caused by secreted metalloproteinases, especially by gelatinase. The partial dissolution of the matrix facilitates cell penetration. Active locomotion and squeezing through the residual membrane matrix allows the cells to penetrate without complete local membrane destruction. The last step involves migration of the cells through the connective tissue barrier to the site of infection. The type I collagen fibres which form this loose stroma tissue are no obstacle and can be pushed aside without proteolytic degradation. PMID- 1515085 TI - Regulation of proteinase activation in mammalian tissues. AB - A lot of new results have been published on activation of one or more proteinases in mammalian tissues. Explanation of proteinase activation without invasion of leukocyte during atrophy of mammalian tissues is the subject of the present study. The mechanism of activation process can be divided into two parts. The first one consists of modification of proteinases and their inhibitors by oxidation or reduction including oxygen free radical reactions. The second part of activation is a cascade or cycle including limited proteolysis of proenzymes and/or proteinase inhibitors. The hypothetic system of proteinase activation can give a hope for regulation of proteinase activity in mammalian tissues under pathological- or pathologic-like conditions as during exhausting exercise. PMID- 1515086 TI - Endocytosis by liver cells during suppression of intralysosomal proteolysis. AB - The lysosomotropic agent chloroquine is widely used as a specific inhibitor of intralysosomal proteolysis in isolated hepatocytes. It was shown that in vitro chloroquine reversibly inhibited purified cathepsins H, B, L in concentrations less than those observed inside lysosomes in vivo. However, administration of high doses of chloroquine to rats (30-50 mg/kg i.p. as a single or repeated injections) was followed by increased cathepsin D and cysteine proteinase activities, as well as other lysosomal enzymes. Chloroquine administration did not induce any changes of carbon particles phagocytosis by liver cells (macrophages); modifications of fluid-phase (125I-PVP uptake) and receptor mediated endocytosis (125I-asialo-fetuin uptake) were noted. Chloroquine administered in vivo reproduced some symptoms of lysosomal storage diseases (especially during repeated drug administration). PMID- 1515087 TI - Proteolytic inactivation of alpha 1-proteinase inhibitor in vivo: detection, characterization and quantitation of the main fragment excreted in the urine of leukemia patients. AB - During the search for a therapy response parameter in patients with acute myeloid leukemia, we observed the appearance of a 41 kDa glycoprotein band in the urines of these patients under therapy. To investigate the nature of this molecule and to develop a specific detection system, the protein was isolated and antibodies were raised. Urines and sera of patients and healthy subjects were screened for crossreacting proteins by immunoblotting. Only the leukemia patients showed the urinary 41 kDa protein plus a 53 kDa band. In all sera, including those from healthy donors, a 53 kDa protein was intensely stained. Isolation of the plasma protein and sequence analysis of the urinary protein revealed that alpha 1 proteinase inhibitor is the crossreacting plasma protein and that the 41 kDa molecule is proteolytically modified alpha 1-PI, which has lost its antitryptic activity. Cleavage occurred in the N-terminal part as well as in the reactive site loop of the inhibitor. The 41 kDa truncated inhibitor was also found in the leukemic blast cells. A densitometric method is described for the quantitation of the molecule in the nanomolar range. PMID- 1515088 TI - Cysteine endopeptidases and their inhibitors in malignant progression of rat embryo fibroblasts. AB - Cathepsins B and L and their endogenous inhibitors were evaluated in rat embryo fibroblast lines which have been developed as a model system for the study of malignant progression and metastatic capability. Three groups of lines were analyzed: 1) immortalized/non-tumorigenic, 2) tumorigenic/metastatic lines transfected with c-Ha-ras, and 3) metastatic revertants transfected with c-Ha ras+the E1A region of adenovirus type 2. The metastatic revertants are tumorigenic, but non-metastatic. No correlation was seen between tumorigenicity and metastatic potential and the level of expression of cathepsin B or the subcellular distribution of cathepsins B and L. However, cathepsin L activity was increased 2-fold in the 4R metastatic line. Although transfection of aneuploid 3T3 fibroblasts with ras has been shown to increase the expression of cathepsin L and cathepsin B, transfection of the diploid rat embryo fibroblasts with ras did not correlate with increased expression of cathepsin L or cathepsin B. However, ras transfection of the rat embryo fibroblasts was associated with a significant (4-15-fold) decrease in the activity of heat-stable cysteine endopeptidase inhibitors. Thus, in tumorigenic rat embryo fibroblast lines, regulation of the activities of cysteine endopeptidases by their endogenous inhibitors may be compromised, resulting in increased effective activities of the cysteine endopeptidases. PMID- 1515089 TI - Cystatins and cathepsins in breast carcinoma. AB - The increased expression of proteolytic systems is one of the characteristics of transformed and malignant cells and their evaluations in whole tumor homogenates were considered as possible diagnostic and/or prognostic factors. Abnormal intracellular distribution, increased activities and secretion of cysteine proteinases (CPs) cathepsin B (Cat B) and L (Cat L), were associated with tumor progression. In the present study of matched pairs of breast carcinoma and normal breast tissue, the activities of Cat B and Cat L in breast carcinoma homogenates were found to be 20 and 50 fold higher, respectively, than in normal tissues. In contrast, a decrease in total inhibitory activity of cysteine proteinase inhibitors (CPIs) was observed but an average ratio between tumor and normal tissues was only 0.75. One of the CPIs, stefin A, was also determined immunochemically. The activities of CPs and CPIs were compared to the increased levels of cathepsin D (Cat D) activities in individual patients, but no statistically significant correlations were found. We correlated CPs and CPIs with morphological and receptor data as well as the axillary lymph node metastases. There was no statistical correlation of CP and CPIs with the number of lymph node metastases. However, highly elevated levels of Cat B and Cat L and lowered CPI activities in tumor cytosols were often associated with poorly differentiated carcinomas and those with negative ER and PR values. We conclude that cysteine-dependent proteolysis may play an important role in breast tumors. PMID- 1515090 TI - Growth-related proteinases in cultured human tumour cells. AB - The proliferation of normal cells, and of early-passage cells from tumours, is inhibited as a consequence of inhibition of a cell-surface proteinase activity. In contrast, established tumour cell lines are usually resistant to these effects. It has previously been suggested that the change from sensitivity to resistance may be a consequence of tumour progression, but experiments with an additional three human tumour cell cultures show that this change is not inevitable. PMID- 1515091 TI - Tumor-associated urokinase-type plasminogen activator: biological and clinical significance. AB - Evidence has accumulated that invasion and metastasis in solid tumors require the action of tumor-associated proteases, which promote the dissolution of the surrounding tumor matrix and the basement membranes. Receptor-bound urokinase type plasminogen activator (uPA) appears to play a key role in these events. uPA converts plasminogen into plasmin and thus mediates pericellular proteolysis during cell migration and tissue remodeling under physiological and pathophysiological conditions. uPA is secreted as an enzymatically inactive proenzyme (pro-uPA) by tumor cells and stroma cells. uPA exerts its proteolytic function on normal cells and tumor cells as an ectoenzyme after having bound to a high-affinity cell surface receptor. After binding, pro-uPA is activated by serine proteases (e.g. plasmin, trypsin or plasma kallikrein) and by the cysteine proteases cathepsin B or L, resp. Receptor-bound enzymatically active uPA converts plasminogen to plasmin which is bound to a different low-affinity receptor on tumor cells. Plasmin then degrades components of the tumor stroma (e.g. fibrin, fibronectin, proteoglycans, laminin) and may activate procollagenase type IV which degrades collagen type IV, a major part of the basement membrane. Hence receptor-bound uPA will promote plasminogen activation and thus the dissolution of the tumor matrix and the basement membrane which is a prerequisite for invasion and metastasis. Tissues of primary cancer and/or metastases of the breast, ovary, prostate, cervix uteri, bladder, lung and of the gastrointestinal tract contain elevated levels of uPA compared to benign tissues. In breast cancer uPA and PAI-1 antigen in tumor tissue extracts are independent prognostic factors for relapse-free and overall survival. PMID- 1515092 TI - Amyloid formation from immunoglobulin chains. PMID- 1515093 TI - Hydrophobic properties of an amyloidogenic kappa I-Bence Jones protein fragment in charge shift electrophoresis. AB - Increase in hydrophobicity of amyloid-A protein as compared to the serum amyloid A precursor protein has been demonstrated with charge shift electrophoresis. Charge shift electrophoresis was applied to the kappa-Bence Jones protein MEV, to amyloid-like fibrils generated in vitro by limited proteolysis of MEV and to an isolated, naturally occurring isolated A lambda (ULI) amyloid fibril protein, to see whether an increase in hydrophobicity is also found in to the immunoglobulin type amyloid. The results also demonstrate here an increase in hydrophobicity during amyloidogenesis of immunoglobulin-derived amyloid fibril proteins, here. PMID- 1515094 TI - Plasma lactoferrin content in neutropenic patients: effects of treatment with recombinant granulocyte-macrophage colony-stimulating factor. AB - Plasma lactoferrin content was measured before and after therapy with recombinant granulocyte-macrophage colony-stimulating factor in five patients with aplastic anaemia, six with myelodysplasia, and three with prolonged, severe, chemotherapy induced neutropenia. Before therapy plasma lactoferrin content was uniformly low. However, patients with aplastic anemia and those with chemotherapy-induced neutropenia had a normal lactoferrin:neutrophil ratio. The low levels of plasma lactoferrin thus reflected the low granulocyte mass. On the other hand, patients with myelodysplasia also had reduced lactoferrin:neutrophil ratios, suggesting qualitative/quantitative abnormalities of neutrophil lactoferrin production. After treatment with granulocyte-macrophage colony-stimulating factor, plasma lactoferrin levels increased in patients with aplastic anemia and in those with chemotherapy-induced neutropenia who showed a neutrophil response to treatment. In these patients, the lactoferrin:neutrophil ratio became elevated, suggesting increased synthesis/release of lactoferrin from neutrophils. However, patients with myelodysplasia continued to show depressed lactoferrin:neutrophil ratios, even when there had been an increase in granulocyte count, suggesting persistent abnormalities of neutrophil lactoferrin production/release. The implications of these findings for treatment of neutropenic patients with granulocyte-macrophage colony-stimulating factors are discussed. PMID- 1515095 TI - Biologic and therapeutic efficacy of mafosfamide in patients with metastatic renal cell carcinoma. AB - It is well known that oxazaphosphorines [e.g., cyclophosphamide and 4 hydroperoxycyclophosphamide (mafosfamide)] are potent immunosuppressive agents. Under the proper conditions, they can potentiate immune responses as well. Immunomodulation represents a major breakthrough in the management of chemotherapy-resistant tumors. Thus, we evaluated the clinical and laboratory sequelae of low to intermediate doses (100-1000 mg/m2) of mafosfamide administered to 16 patients. Four weeks after therapy, one patient had a complete remission, eight patients presented with stable disease, and seven patients did not respond. Clinical and laboratory toxicity was mild and totally reversible, and therapy was well tolerated in all patients. Analyses of phenotypic cell surface antigens on circulating peripheral blood mononuclear cells showed inconsistent alterations of the CD4/CD8 ratio, initial depletion with later rebound of CD8+ cells, increase of CD20+ cells, and a mafosfamide dose-dependent regulation of natural killer-like cells as characterized by CD16 and CD56 positivity. Cell-mediated cytotoxicity against K562 target cells peaked 1 day after therapy and was most pronounced in patients who had received 300 mg/m2 mafosfamide, whereas cytotoxicity against Daudi targets was essentially unchanged, consistent with an increase in natural killing activity without augmentation of lymphokine activated killing. We conclude that mafosfamide administration at low to intermediate doses can be performed with good safety and tolerance; immunophenotypic analyses and cytotoxicity assays showed most pronounced alterations in patients receiving low doses of mafosfamide. These observations support the use of mafosfamide in the attempt to augment antitumor immune responses. PMID- 1515096 TI - Interleukin-2 increases the antibody response in patients receiving autologous intralymphatic tumor cell vaccine immunotherapy. AB - The production of tumor-binding antibodies was studied in a group of cancer patients undergoing active specific immunotherapy with irradiated, cholesterol treated, cell culture-derived autologous tumor cells injected by the intralymphatic route. Fifteen patients were analyzed: nine patients (four melanoma, one breast, one sarcoma, one colon, and one undifferentiated cancer) received three injections of 10 to 15 x 10(6) tumor cells, spaced 2 weeks apart, and six patients (two melanoma, two renal, one breast, and one colon cancer) received tumor cells admixed with 3 x 10(6) U recombinant interleukin-2 (IL-2) (Proleukin, Cetus, Emeryville, CA, USA) plus a 10-day intravenous infusion of 15 x 10(6) U/kg/day IL-2 after each immunization. Serum antibody binding to autologous tumor cells was measured at 2 and 4 weeks after initiation of therapy using an enzyme-linked immunosorbent assay with patient serum being added to adherent tumor cells bound to 96-well microtiter plates. After 4 weeks, we found a significant difference (0.02 less than P less than 0.04) in serum titer in the group receiving IL-2 (33% mean increase) compared with the non-IL-2 group (8% mean increase). Although neither group showed clinical improvement in response to the therapy, the results clearly demonstrated the efficacy of IL-2 in augmenting patient antibody response to autologous intralymphatic tumor cell immunization. PMID- 1515097 TI - Genetic engineering of anticolorectal carcinoma Fv molecule in myeloma cells. AB - The anti-TAG72 Fv molecule composed of a heterodimer of both heavy- and light chain variable domains was produced by the construction of the expression vector mpSV2neo-EP1-Fv72.3. This vector contained the neo gene as a selection marker, the murine immunoglobulin heavy chain promoter (P1), enhancer (E), the SV40 polyadenylation signal region, and the murine cDNA fragments of VH and VL regions amplified and cloned directly from the B72.3 hybridoma RNA by the polymerase chain reaction technique. Termination codons were introduced into the 3' end of both VH and VL regions. The expression vector was transfected into the SP2/0 cell line. The Fv72.3 molecules were purified by the rabbit anti-B72.3 idiotype antibody affinity column, and retained the binding reactivity for the TAG72 antigen. The small size of Fv72.3 molecule (25 kD) makes it attractive for structural studies and immunodetection of cancers. PMID- 1515098 TI - Modulation of hematologic and immunologic effects of high dose chemotherapy by interleukin-2 in a murine tumor model. AB - To determine if intensive chemotherapy consisting of cyclophosphamide (C), etoposide (E), and cisplatin (P) (CEP) may be usefully combined with recombinant human interleukin-2 (rhIL-2), we examined a murine tumor model designed to approximate a common clinical situation: macroscopic, drug-resistant cancer. Using C57BL/6 mice with extensive tumor burden 10 days after intravenous B16 melanoma cell injection, we observed (1) C, E, and P synergize to enhance survival but do not cure mice at the highest tolerable dose (C = 200 mg/kg, E = 60 mg/kg, and P = 3 mg/kg); (2) rhIL-2 at 3 x 10(5) U (subcutaneously) daily for 4 days administered 10-18 days after B16 injection significantly improves survival; (3) CEP plus rhIL-2 is more effective than CEP alone only when rhIL-2 is administered before CEP; (4) CEP suppresses IL-2-induced lymphokine-activated killer cell activity in the spleen; and (5) rhIL-2 protects mice incompletely from the immunologic and hematologic suppression of CEP. Our results suggest that intensive chemotherapy combined with rhIL-2 may be beneficial. The success of any such combination may be schedule dependent. PMID- 1515099 TI - Augmentation of human lymphokine-activated killer cell activity in splenic lymphocytes by the combination of low-dose interleukin 2 plus interleukin 3. AB - The effect of interleukin 3 (IL-3) on lymphokine-activated killer cell (LAK) generation in splenic lymphocytes was examined in patients with gastric cancer or idiopathic thrombocytopenic purpura (ITP). IL-3 alone did not induce any significant LAK activity from splenic lymphocytes. However, IL-3 addition to the culture with low-dose IL-2 significantly augmented the activity of LAK cells. Spleen cells precultured with IL-3 for 2 days and then added to IL-2 became more potent LAK cells than the spleen cells cultured with the same doses of IL-3 plus IL-2. Phenotypic analysis using flow cytometry demonstrated that IL-2 alone increased in cells expressing CD2+, -11+, and -16+ cells, whereas IL-3 plus IL-2 induced the expansion of CD3+ and CD8+ cells in addition to CD2+, -11+, and -16+ cells. These results suggest that IL-3 plus IL-2 phenotypically induces not only natural killer-like LAK cells (CD2+, -11+, and -16+) but T cell-like LAK cells (CD3+ and -8+). We are now investigating the characteristics of immature T cell populations in the spleen responsive to IL-3 using T-cell receptor antibody. PMID- 1515100 TI - Modulation of viral infections by cytokines. AB - The survival of a host challenged by viral infection depends on many factors. Some are specific, such as antiviral T-cell and B-cell responses. Others are nonspecific, such as intrinsic cellular resistance, macrophage activation, and activation of humoral protective mechanisms (e.g., complement, coagulation, etc.). Cytokines are important mediators and regulators of both types of host response. Furthermore, orchestration of specific humoral and cellular immune responses requires the participation of many cytokines. Details of the complex and overlapping roles that cytokines play in specific immune responses is beyond the scope of this review. Instead, this review will focus on the nonspecific antiviral effects of cytokines. PMID- 1515101 TI - Metastases to skeletal muscles and interferon treatment. AB - Blood-borne metastases to a skeletal muscle are rare and may originate in various primary tumors. Recurrent solitary metastasis of renal cell carcinoma, and metastatic lesion as part of disseminated malignant melanoma in skeletal muscles are reported in two patients. In both cases interferon treatment with or without chemotherapy failed in arresting the disease. PMID- 1515102 TI - Structure of RG-12561 dichloromethane solvate and a diastereomer. AB - (III): [4 alpha,6 beta(E)]-(+-)-6-(2-[2-(4-Fluoro-3-methylphenyl)- 4,4,6,6 tetramethyl-1-cyclohexen-1-yl]ethenyl)-4-hydroxytetrahy dro pyran-2-one (RG 12561) dichloromethane solvate, 2C24H31FO3.CH2-Cl2, Mr = 857.94, triclinic, Pl, a = 11.7413 (5), b = 13.0279 (5), c = 16.2332 (9) A, alpha = 99.456 (4), beta = 94.217 (4), gamma = 101.893 (4) degrees, V = 2381.9 (4) A3, Z = 4 [four molecules of (III)+two molecules of solvent per unit cell], Dx = 1.195 g cm-3, Cu K alpha, lambda = 1.54178 A, mu = 16.69 cm-1, F(000) = 912, T = 293 K, final R = 0.053, wR = 0.060 for 4031 reflections with I greater than 3 sigma(I). (IV): [4 beta,6 alpha(E)]-(+-)-6-(2-[2- (4-Fluoro-3-methylphenyl)-4,4,6,6-tetramethyl-1-cyclo hexen-1-yl]e thenyl)-4- hydroxytetrahydropyran-2-one, C24H31FO3, Mr = 386.51, triclinic, Pl, a = 6.054 (2), b = 12.931 (2), c = 14.838 (3) A, alpha = 67.70 (2), beta = 85.75 (2), gamma = 82.85 (2) degrees, V = 1066.0 (8) A3, Z = 2, Dx = 1.203 g cm-3, Cu K alpha, lambda = 1.54178 A, mu = 6.86 cm-1, F(000) = 414, T = 293 K, final R = 0.073, wR = 0.081 for 1588 reflections with I greater than 3 sigma(I). (III) is a potent HMG-CoA reductase inhibitor and has the potential to function as a superior hypocholesterolemic agent; (IV) lacks this activity. (III) and (IV) have different conformations and molecular-model calculations suggest that crystal-packing effects are primarily responsible for the overall conformation of (IV). The principal intermolecular contacts are hydrogen bonds of the type O-H...O = C. PMID- 1515103 TI - Structures of methyl 7-phenyldibenz[a,j]anthracene-14-carboxylate and methyl 7 phenylbenzo[1,2-h:5,4-h']diquinoline-14-carboxylate: twisted aromatic spacers containing bay-region esters. AB - C30H20O2, (1), Mr = 412.49, triclinic, P1 (Ci1), a = 11.301 (7), b = 12.069 (3), c = 9.777 (2) A, alpha = 96.12 (2), beta = 111.59 (4), gamma = 114.68 (3) degrees, V = 1072 (2) A3, Z = 2, Dx = 1.278 g cm-3, lambda(Mo K alpha) = 0.71073 A, mu = 0.73 cm-1, F(000) = 432, T = 299 K, final R = 0.065 for 1231 observed reflections. C28H18N2O2, (2), Mr = 414.46, monoclinic, I2/a (C2h6), a = 20.039 (10), b = 11.762 (8), c = 19.850 (5) A, beta = 117.61 (3) degrees, V = 4146 (8) A3, Z = 8, Dx = 1.328 g cm-3, lambda(Mo K alpha) = 0.71073 A, mu = 0.79 cm-1, F(000) = 1728, T = 298 K, final R = 0.048 for 1924 observed reflections. Aromatic system (1) is highly twisted (43 degrees from end to end) in a helical sense. Half of aromatic system (2) is nearly planar with the ester C atom, whereas the other half is twisted by ca 27 degrees for planarity. PMID- 1515104 TI - Structure of N-acetyl-L-leucyl-L-prolinamide monohydrate. AB - C13H23N3O3.H2O, Mr = 287.36, orthorhombic, P2(1)2(1)2(1), a = 6.3863 (8), b = 14.346 (2), c = 17.247 (2) A, V = 1580.1 (6) A3, Z = 4, Dx = 1.208 g cm-3, lambda(Cu K alpha) = 1.54178 A, mu = 7.04 cm-1, F(000) = 624, room temperature, final R = 0.037 for 1693 reflections with I greater than or equal to 2.5 sigma (I) and 257 variables. The peptide linkage is in a trans conformation. The pyrrolidine ring adopts a puckered C gamma-endo conformation and the leucine side chain is in a twisted [g-(tg-)] conformation. The crystal packing is stabilized by a three-dimensional network of hydrogen bonds which involve all the donor groups. The water molecule plays an important part in the crystal packing, being engaged in three hydrogen bonds with different N-acetylamide molecules. PMID- 1515105 TI - Synthesis and structure of new bronchospasmolytic agents. I. AB - The crystal structures of two phenylethanolamines showing bronchospasmolytic activity have been determined at room temperature [293 (2) K]. Crystal data are as follows: 11-morpholinotricyclo[6.3.0.0(2,7)]undeca-2,4,6-trien-l-ol (3), C15H19NO2, M(r) = 245.3, triclinic, P1, a = 10.360 (5), b = 12.169 (5), c = 12.488 (4) A, alpha = 95.14 (10), beta = 108.49 (12), gamma = 114.69 (5) degrees, V = 1311 (2) A3, Z = 4, Dx = 1.243 Mg m-3, Cu K alpha 1 radiation, lambda = 1.540562 A, mu = 0.618 mm-1, F(000) = 528, R = 0.0537 for 3009 observed reflections; 4-morpholino-1,2-benzocyclononen-3-ol monohydrate (5), C17H25NO2.H2O, M(r) = 293.4, monoclinic, P2(1)/c, a = 10.063 (9), b = 19.398 (5), c = 8.670 (5) A, beta = 110.56 (1) degree, V = 1585 (2) A3, Z = 4, Dx = 1.230 Mg m-3, Mo K alpha 1 radiation, lambda = 0.709300 A, mu = 0.0778 mm-1, F(000) = 640, R = 0.0376 for 1407 observed reflections. The stereochemistry of compound (3) is found to be 'all cis', which allows the mechanism of formation of these compounds to be interpreted. The various aspects of the conformations of these molecules are discussed. PMID- 1515106 TI - Structure of ribonuclease T1 complexed with zinc(II) at 1.8 A resolution: a Zn2+.6H2O.carboxylate clathrate. AB - In order to study the inhibitory effect of Zn2+ on ribonuclease T1 [RNase T1; Itaya & Inoue (1982). Biochem. J. 207, 357-362], the enzyme was cocrystallized with 2 mM Zn2+, pH 5.2, from a solution containing 55% (v/v) 2-methyl-2,4 pentanediol. The crystals are orthorhombic, P2(1)2(1)2(1), a = 48.71 (1), b = 46.51 (1), c = 41.14 (1) A, Z = 4, V = 93203 A3. The crystal structure was determined by molecular replacement and refined by restrained least-squares methods based on Fhkl for 8291 unique reflections with Fo greater than or equal to 1 sigma (Fo) in the resolution range 10 to 1.8 A and converged at a crystallographic R factor of 0.140. The Zn2+ is not bonded to the active site of RNase T1, probably because the His40 and His92 side chains are protonated. Zn2+ occupies the same site as Ca2+ in a series of crystal structures of free and nucleotide-complexed RNase T1. It is coordinated to Asp15 carboxylate and to six water molecules forming a dodecahedron of square antiprismatic form. The Zn2+...O distances are approximately 2.5 A, suggesting that Zn2+ is clathrated and not coordinated, which would require distances of 2.0 A. PMID- 1515107 TI - Structure determination and refinement of homotetrameric hemoglobin from Urechis caupo at 2.5 A resolution. AB - A 5 A resolution multiple isomorphous replacement solution for hemoglobin isolated from Urechis caupo revealed a previously unobserved quaternary structure for tetrameric hemoglobin [Kolatkar, Meador, Stanfield & Hackert (1988). J. Biol. Chem. 263(7), 3462-3465]. We report here the structure of Urechis hemoglobin in the cyanomet state refined to 2.5 A resolution by simulated annealing yielding R = 0.148 for reflections F greater than 3 sigma between 5.0 and 2.5 A resolution. The starting model was fitted to a map originally derived from multiple wavelength anomalous-dispersion phases to 3 A resolution that was then subjected to cyclic twofold molecular averaging and solvent flattening. Structural analysis of the resultant model shows that the unique quaternary assemblage is possible due to several favorable interactions between subunits, including salt links, hydrophobic pockets and interactions mediated by bound water. The tetramer is stabilized by subunit-subunit interactions between the G/H turns and D helices within the crystallographic dimer, and the A/B turn regions and E helices between subunits related by a molecular twofold axis. Interestingly, each subunit has one cysteine residue (Cys21) located in the A/B turn. These twofold-related cysteinyl residues are near enough to one another to form a disulfide bridge but do not. PMID- 1515108 TI - Structure determination of turkey egg-white lysozyme using Laue diffraction data. AB - The three-dimensional structure of turkey egg-white lysozyme (TEWL) has been solved and refined at 2.5 A resolution using X-ray data collected by the Laue method. This is the first protein structure determination undertaken using Laue diffraction data. A re-examination of the existing structure of TEWL was necessary when attempts to refine an atomic model based on the C alpha positions in the Protein Data Bank (entry 1LZ2) failed. The correct orientation and position of the turkey lysozyme molecules within the crystallographic unit cell were determined by molecular replacement using a refined model of the homologous hen egg-white lysozyme crystal structure. After modification of the model to reflect the differences in amino-acid sequence between the chicken and turkey enzymes, the structure was subjected to crystallographic refinement using the simulated-annealing refinement technique and conventional least-squares refinement. This yielded a final residual of R = 20.7%. This crystal form is of potential interest for time-resolved crystallographic studies since the amino acid residues involved in catalysis (Asp52 and Glu35) are accessible to solvent and not blocked by crystal contacts. PMID- 1515109 TI - Relationship of three-dimensional structure of muscarinic antagonists to antimuscarinic activity: structure of thiodeacylaprophen hydrochloride. AB - C20H28NS+.Cl-, 2-(diethylamino)ethyl 1,1-diphenylethyl sulfide hydrochloride (thiodeacylaprophen hydrochloride), M(r) = 349.9, orthorhombic, P2(1)2(1)2(1), a = 8.933 (2), b = 11.710 (3), c = 18.934 (4) A, V = 1980.6 (7) A3, Z = 4, Dx = 1.173 g cm-3, Cu K alpha, lambda = 1.54178 A, mu = 26.70 cm-1, F(000) = 752, room temperature, final R = 4.1% for 1417 reflections with /Fo/ greater than 3 sigma (F). Thiodeacylaprophen crystallized as a tertiary amine hydrochloride salt. The S--C--C--N+ segment adopts a trans configuration as does one of the Cphenyl--C--S -C segments. A comparison of the structure of thiodeacylaprophen with the crystal structures of potent antimuscarinic agents suggests that the relatively weak antimuscarinic activity of thiodeacylaprophen compared to atropine and aprophen may be substantially due to the short intramolecular S...N+ distance of 4.106 (6) A. Other contributing structural factors may include the direction of the N+--H bond and restricted accessibility of the sulfur atom for interatomic interactions. PMID- 1515110 TI - X-ray studies on anti-tumour triazenes. Structures of 1-(4-carbamoylphenyl)-3,3 dimethyltriazene 1-oxide and 3,3-dimethyl-1-(4-nitrophenyl)triazene. AB - The molecular structures of the title compounds have been determined by X-ray crystallographic methods. The analyses revealed differences in the geometry, and by inference the bond delocalization in these two triazenes owing to the presence in the 1-oxide structure of an N-O bond. The geometries are compared to the crystal structures of the isomeric 3-oxides [Kuroda & Wilman (1985). Acta Cryst. C41, 1543-1545; Neidle, Webster, Kuroda & Wilman (1987). Acta Cryst. C43, 674 676] which shows the dominance of an alternative tautomeric equilibrium for the triazene groups. PMID- 1515111 TI - Electrostatic properties of 1-methyluracil from diffraction data. AB - 1-Methyluracil (1-methyl-2,4-dioxopyrimidine), C5H6-N2O2, M(r) = 126.12, orthorhombic, Ibam, a = 13.188 (6), b = 13.175 (5), c = 6.214 (3) A, V = 1079.7 (8) A3, Z = 8, Dx = 1.552 g cm-3, lambda (Mo K alpha) = 0.7107 A, mu = 1.317 cm 1, F(000) = 528, T = 123 K, R(F2) = 0.068 for 2996 reflections with sin theta/lambda less than 1.08 A-1. The electronic charge-density distribution has been analyzed in terms of Stewart's rigid pseudoatom model, using restricted Slater radial functions and angular multipole terms extending to octapoles for C, N and O, and quadrupoles for H pseudoatoms. Three different structure refinements have been carried out based on two X-ray diffraction data sets from different crystals collected at temperatures differing by about 20 K. The molecular dipole moment is 6.4 (27) D. Maps of the electrostatic potential for a molecule isolated from the crystal show that atoms O2 and O4 confer overall electro-negativity on one side of the molecule while the CH groups and the C1 methyl group confer electropositivity on the other. For the centrosymmetric hydrogen-bonded dimer (N3 H3...O4'; H...O distances 1.77 A) the electrostatic potential shows electropositive bridges between the molecules. These features are lacking for the C-H...O interactions (distances H6...O2, 2.37; H11...O4, 2.34 A). The electron density and its Laplacian have been determined at the intramolecular bond critical points and also for the intermolecular H...O interactions. Values for the former are characteristic of covalent bonds. Values of the electron density and Laplacian for the C-H...O interactions are very small and have little or no significance in terms of their e.s.d.'s. The electrostatic energy of interaction for the N-H...O hydrogen-bonded dimer is -10 (12) kJ mol-1. The attractive electrostatic energy increases to -67 (33) kJ mol-1 for a centrosymmetric planar tetramer in which the C-H...O interactions are also formed. PMID- 1515112 TI - Crystallization and preliminary X-ray analysis of human endothelin. AB - Endothelin, a potent regulator of vasoconstriction and hypertension, is a naturally produced peptide of 21 amino acids containing two disulfide bonds. We have crystallized endothelin from humans using the vapor-diffusion technique, characterized the crystals by X-ray diffraction analysis, and have collected the X-ray intensities to a resolution of 1.8 A. The crystals, which demonstrate physical properties similar to most protein crystals and have a comparable solvent content, are hexagonal prisms that frequently grow to lengths of 400 microns and widths of 150 microns. The space group of the crystals is P6(1)22 (or P6(5)22), with a = 27.4, c = 79.6 A. There is one molecule of endothelin in the asymmetric unit of the crystals. PMID- 1515113 TI - Crystallization studies of the catalytic subunit of cAMP-dependent protein kinase: crystals of murine recombinant catalytic subunit and a mutant, Cys 343--- Ser, diffract to 2.7 A resolution. AB - The recombinant mouse catalytic subunit of cAMP-dependent protein kinase, expressed and purified from E. coli, has been successfully cocrystallized as a binary complex with an inhibitor peptide and as a ternary complex with an inhibitor peptide and MgATP. In contrast to the catalytic subunit obtained from porcine heart, the recombinant catalytic subunit lacks a myristoyl group at the amino terminus and differs in sequence at nine positions out of 350 amino acids. The catalytic activities of the two enzymes, however, are nearly identical. Both enzymes cocrystallized with a 20-amino-acid inhibitor and MgATP; however, the porcine-heart enzyme crystallized in a hexagonal space group (P6(1)22) while the recombinant murine catalytic subunit crystallized in an orthorhombic space group (P2(1)2(1)2(1), a = 73.70, b = 76.26, c = 80.74 A). The orthorhombic crystals of the recombinant catalytic subunit exhibit the best diffraction characteristics of all catalytic subunit crystals obtained so far: 2.7 A resolution. Unlike the mammalian porcine-heart enzyme, no crystals of the recombinant apo-enzyme were obtained under the same crystallization conditions. These results are consistent with earlier conclusions that the catalytic subunit exists in at least two distinct conformational states and furthermore suggests that the inhibitor peptide alone is sufficient to induce the major conformational changes that distinguish the two states. A mutant form of the catalytic subunit where Cys343 was replaced with Ser was also cocrystallized with the 20-amino-acid peptide inhibitor and MgATP, and resulted in an orthorhombic crystal isomorphous to crystals of the unmutated enzyme with a similar diffraction of 2.7 A. PMID- 1515114 TI - Immunosensors in medical diagnostics--major hurdles to commercial success. AB - In the last few years the format of commercial immunoassays has dramatically changed. Automated instruments running up to 180 samples per hour and dry strip or film immunochemistry products are now available. These changes have been precipitated by the need for immunoassays that require less time and skill to perform. To date, no immunosensor technology has been successfully commercialized although a few are purported to be on the brink of being released for sale. Here, B. Manning and T. Maley evaluate the major factors affecting the success of immunosensors. PMID- 1515115 TI - A quartz crystal biosensor for measurement in liquids. AB - The detection of anti-human immunodeficiency virus (HIV) antibodies by means of synthetic HIV peptide immobilized on a piezoelectric quartz sensor is demonstrated. The measurement set-up consists of an oscillator circuit, a suitably modified AT-cut thickness-shear-mode quartz crystal with gold electrodes, which is housed in a special reaction vessel, and a computer controlled frequency counter for the registration of the measured frequency values. The quartz crystal is adapted for a steady operation in liquids at a frequency of 20 MHz. In phosphate-buffered saline solution the oscillator reaches a stability of about 0.5 Hz within a few seconds, of about 2 Hz within 10 min and about 30 Hz within 1 h. The frequency shift due to the adsorption of various proteins to the uncoated sensor surface has been investigated. It can be shown that a stable adsorptive binding of proteins to an oscillating gold surface is feasible and can be used for the immobilization of a receptor layer (e.g. HIV peptide). Specific binding of the anti-HIV monoclonal antibody to the HIV peptide immobilized on the quartz sensor is demonstrated. Control experiments show, however, additional unspecific binding. According to the experiments, the Sauerbrey formula gives a sufficiently accurate value for the decrease of the resonant frequency due to adsorption or binding of macromolecular proteins on the quartz crystal surface. PMID- 1515116 TI - A surface plasmon resonance immunosensor based on the streptavidin-biotin complex. AB - It is shown that a streptavidin monolayer immobilized onto an evaporated gold film with biotin forms the basis of a highly specific sensing element. As an example, we show that by immobilizing the biotinylated antibody sex hormone binding globulin (alpha-SHBG) to the bound streptavidin monolayer a specific sensor for the antigen SHBG is readily fabricated. The interaction between immobilized antibody and corresponding antigen is monitored by surface plasmon resonance spectroscopy and is shown to follow a classic Langmuir isotherm. Detection of SHBG at nanomolar concentrations is demonstrated. PMID- 1515117 TI - A piezoelectric immunobiosensor for atrazine in drinking water. AB - A piezoelectric crystal immunobiosensor has been developed for the assay of atrazine herbicides in drinking water. Determinations from 0.03-100 micrograms l 1 (parts per billion) of atrazine can be made with a relative SD of about +/- 8%. Atrazine antibodies (polyclonal from sheep) are layered onto the gold electrode of 10 MHz piezoelectric crystals, which are precoated with protein A. The sensor is reversible, being reusable for about eight or nine assays. PMID- 1515118 TI - Comparison of colloidal gold electrode fabrication methods: the preparation of a horseradish peroxidase enzyme electrode. AB - In order to prepare biosensing electrodes which respond to hydrogen peroxide, horseradish peroxidase has been adsorbed to colloidal gold sols and electrodes prepared by deposition of these enzyme-gold sols onto glassy carbon using three methods: evaporation, electrodeposition and electrolyte deposition. In the latter method the enzyme-gold sol is applied to the surface of a glassy carbon disk electrode followed by an equal volume of 2 mM CaCl2. The electrolyte causes the sol to precipitate on the electrode surface, producing an immobilized enzyme electrode. Satisfactory electrodes which gave an electrochemical response to hydrogen peroxide in the presence of the electron transfer mediator ferrocenecarboxylic acid were produced by all three methods. Evaporation of horseradish peroxidase-gold sols produced electrodes with the best reproducibility and the widest linear amperometric response range. These electrodes can also easily be stored in a dry state. Although not as good as evaporation, electrodeposition also produced satisfactory electrodes. Electro deposition provides the added advantage that it lends itself to the preparation of multi-enzyme/multi-analyte electrodes by the adsorption of different enzymes to separate gold sols, followed by sequential electrodeposition onto discrete areas of a multichannel electrode. PMID- 1515119 TI - Tissue kallikreins and prostatic diseases in man: new questions. PMID- 1515120 TI - The Jeanne Manery-Fisher Memorial Lecture 1991. Maturation of reticulocytes: formation of exosomes as a mechanism for shedding membrane proteins. AB - The transferrin receptor is a member of a group of reticulocyte surface proteins that disappear from the membranes of reticulocytes as the cells mature to the erythrocyte stage. The selective loss of membrane proteins appears to be preceded by the formation of multivesicular bodies (MVBs). At the reticulocyte stage, many species of mammalian red cells including man, and one nucleated avian species (chicken), contain these intracellular structures in both natural and induced anemias. Also characteristic of blood containing reticulocytes is the presence of circulating vesicles (exosomes), which contain proteins and lipids characteristic of the plasma membrane. These exosomes appear to arise from the contents of the MVBs, after the fusion of MVBs with the plasma membrane. The proteins in the exosomes are those frequently lost during red cell maturation (e.g., transferrin receptor). The major transmembrane proteins (such as the anion transporter) are fully retained into the mature red cell, indicating a highly selective mechanism of recognition of a specific group of proteins. The exosomes are largely devoid of soluble proteins and proteins associated with lysozomes or mitochondria. A speculative model is proposed which addresses the questions of the maturation induced structural changes in a class of membrane proteins, their recognition and selective loss involving exosome formation, and the release of exosomes to the circulation. PMID- 1515121 TI - A comparison of the chilling-stress response in two differentially tolerant cultivars of tomato (Lycopersicon esculentum). AB - The chilling responses of two differentially cold tolerant cultivars of tomato were monitored through in vivo labelling of polypeptides with [35S]methionine, both during a gradual temperature decrease (2 degrees C/day) and also during a rapid cold shock (4 degrees C). The polypeptides were separated by one dimensional sodium dodecyl sulfate-polyacrylamide gel electrophoresis and revealed by fluorography. Both cultivars showed changes in the polypeptide profiles resulting from either chilling treatment. During the gradual temperature decrease, there were few differences exhibited between the two cultivars. However, during cold shock both cultivars showed the altered synthesis of several unique polypeptides. Both cultivars showed the appearance of a 35-kDa polypeptide during the gradual temperature decrease and also during the cold shock. The appearance of three high relative mass polypeptides was found in both cultivars only during the gradual temperature decrease. Treatments with cycloheximide and chloramphenicol suggested that cold-shock polypeptides are both nuclear and organelle encoded. The cold-shock response in roots was different from the response in leaves and between cultivars. A comparison of the two cultivars showed a number of differences in polypeptide synthesis which may be related to increased cold tolerance. PMID- 1515122 TI - Essential fatty acid deficiency lowers the activity of the acetylated low density lipoprotein receptor of rat peritoneal macrophages. AB - We compared phospholipid fatty acid composition, cholesterol ester accumulation, and receptor-mediated binding, internalization, and degradation of acetylated low density lipoprotein (acetyl-LDL) in cultured peritoneal macrophages from rats fed an essential fatty acid deficient or control diet. The deficient diet increased the 5,8,11-eicosatrienoic acid and decreased the omega 6 fatty acid content of macrophage phospholipid relative to control. The deficient diet did not affect macrophage uptake of [1-14C]oleate; however, it lowered the accumulation of intracellular labelled cholesteroyl oleate to 66% of the control. This effect was attributed to a diminution of the specific binding of acetyl-LDL, and not to acetyl-LDL internalization nor to degradation. The results demonstrate the sensitivity of the acetyl-LDL receptor to changes in its membrane environment, brought about through dietary means. PMID- 1515124 TI - Properties of phosphorylated protein intermediates of the bacterial phosphoenolpyruvate:sugar phosphotransferase system. AB - The phosphohydrolysis properties of the following phosphoprotein intermediates of the bacterial phosphoenolpyruvate:sugar phosphotransferase system (PTS) were investigated: enzyme I, HPr, and the IIAGlc domain of the glucose enzyme II of Bacillus subtilis; and IIAGlc (fast and slow forms) of Escherichia coli. The phosphohydrolysis properties were also studied for the site-directed mutant H68A of B. subtilis IIA Glc. Several conclusions were reached. (i) The phosphohydrolysis properties of the homologous phosphoprotein intermediates of B. subtilis and E. coli are similar. (ii) These properties deviate from those of isolated N delta 1- and N epsilon 2-phosphohistidine indicating the participation of neighbouring residues at the active sites of these proteins. (iii) The rates of phosphohydrolysis of the H68A mutant of B. subtilis IIAGlc were reduced compared with the wild-type protein, suggesting that both His-83 and His-68 are present at the active site of wild-type IIAGlc. (iv) The removal of seven N terminal residues of E. coli IIAGlc reduced the rates of phosphohydrolysis between pH 5 and 8. PMID- 1515125 TI - Accumulation of starch in Chlamydomonas reinhardtii flagellar mutants. AB - Paralyzed flagellar mutants pf-1, pf-2, pf-7, and pf-18 of the green alga Chlamydomonas reinhardtii (Dangeard) were shown to store a significantly greater amount of starch than the motile wild type 137c+. The increase in starch storage was significant relative to protein, chlorophyll, and cell number. Analysis of average cell size revealed that the paralyzed mutants were larger than the wild type. This increase in storage molecule accumulation supports an inverse relationship between chemical energy storage and energy utilization for biomechanical/motile cellular functions. Chlamydomonas reinhardtii provides a useful model for studies of the role of cytoskeletal activity in the energy relationship and balance of organisms. PMID- 1515123 TI - N-(4-chlorophenyl)-N-hydroxy-N'-(3-chlorophenyl)urea, a general reducing agent for 5-, 12-, and 15-lipoxygenases and a substrate for their pseudoperoxidase activities. AB - Lipoxygenases contain a nonheme iron that undergoes oxidation and reduction during the catalytic cycle. The conversion from the Fe3+ enzyme form to the Fe2+ form can be achieved using reducing inhibitors, a reaction that can be reversed with lipid hydroperoxides. The present study describes the properties of N-(4 chlorophenyl)-N-hydroxy-N'-(3-chlorophenyl)urea (CPHU), which functions as a reducing agent for various lipoxygenases and stimulates the degradation of lipid hydroperoxide catalyzed by these enzymes (pseudoperoxidase activity). CPHU was a substrate for the pseudoperoxidase reaction of purified soybean lipoxygenase-1 with apparent Km values for CPHU and 13-hydroperoxy-9,11-octadecadienoic acid (13 HpODE) of 14 and 15 microM, respectively. CPHU was converted during the pseudoperoxidase reaction to a mixture of products that can be resolved by reverse-phase high pressure liquid chromatography. By comparison with the chemical reaction of CPHU and potassium nitrosodisulfonate, the major enzymatic reaction product was tentatively identified as a one-electron oxidation product of CPHU. At low concentrations (50 microM), dithiothreitol completely protected against the degradation of hydroxyurea without inhibiting the pseudoperoxidase reaction. Under these conditions, the rate of the pseudoperoxidase reaction with CPHU as a substrate can be quantitated by the change in absorbance at 234 nm owing to the consumption of 13-HpODE. In addition to soybean lipoxygenase-1, CPHU was found to be a substrate for the pseudoperoxidase activities of purified recombinant human 5-lipoxygenase and porcine leukocyte 12-lipoxygenase. The results are consistent with CPHU reacting with lipoxygenase by a one-electron oxidation to generate the ferrous enzyme form and the nitroxide radical, which could be reduced back to CPHU by DTT.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1515126 TI - The effect of epidermal growth factor on liver lipid peroxidation and glutathione levels in lobectomized rats. AB - Epidermal growth factor (EGF) is a growth-promoting polypeptide which is found in highest levels in male mice in the submaxillary gland. It may also be a key factor in regeneration of the liver. We performed experiments with 18 male Wistar rats, divided into three groups. Hepatic left lobectomy (%30) was performed on the first group of rats. This group received an intraperitoneal injection of EGF for 7 days. The second group was the control group into which normal saline was injected for 7 days. The third group was sham-operated. On days 5 and 7 tomographic studies of liver were performed. On day 7 EGF levels, lipid peroxidation, and glutathione in liver were measured in all of the rats. While serum EGF levels did not show any significant change, the levels of lipid peroxide were decreased and glutathione was increased. Tomographic measurements indicated that administration of EGF increased the amount of regeneration. PMID- 1515127 TI - A simple method using PCR for direct sequencing of genomic DNA from frozen tumor tissue embedded in optimal cutting temperature compound. AB - Described here is a three-day protocol that directly yields DNA sequence after isolating and PCR amplifying genomic DNA from a small sample of frozen nasopharyngeal carcinoma tissue embedded in optimal cutting temperature (OCT) compound. The method is consistently successful, reproducible and will facilitate the rapid analysis of DNA sequence from very small samples. PMID- 1515128 TI - Detergents inhibit chloramphenicol acetyl transferase. AB - Potent inhibition of chloramphenicol acetyl transferase (CAT) by Triton X-100 and Nonidet P-40 was observed. The CAT activity was also moderately inhibited by sodium deoxycholate and sodium dodecyl sulfate, and least by Tween 20. Detergents should, therefore, not be used for cell lysate preparation when CAT activity is used as the reporter in a transient expression experiment. PMID- 1515129 TI - A useful modification of cDNA that enhances purification of recombinant protein. AB - With the availability of new and improved DNA vectors for producing large amounts of proteins by recombinant DNA technology, there is a growing need for efficient recovery of the desired protein, often from liters of culture medium. In this report, we describe a relatively simple modification of recombinant cDNA, that, in combination with immobilized metal affinity chromatography, is a rapid, inexpensive and highly effective method for enriching or purifying a desired protein. PMID- 1515130 TI - Rapid high resolution western blotting: from gel to image in a single day. AB - A streamlined protocol is described that allows high sensitivity antigen detection by Western blotting in a single day. The choice of membrane blotting matrix, as well as blocking reagents, has been optimized in order to allow rapid development of the blot with chemiluminescent reagents. The entire process, from gel to blot to a permanent, hard copy image on x-ray film, can be accomplished within six hours. PMID- 1515131 TI - Production of polyclonal antibodies in rabbits is simplified using perforated plastic golf balls. AB - Production of polyclonal antibodies in the lumen of a perforated golf ball implanted surgically under the skin of a rabbit offers advantages over conventional techniques. Less stress is placed on the rabbit because bleeding is eliminated, complete adjuvants are not used and animal handling is minimized. The technique also offers the advantage that large amounts of antibody-containing fluid can be removed easily from the ball. In this report we describe the surgical protocol and demonstrate use of this technique to produce high-titered antibodies to plant and plant viral proteins. PMID- 1515132 TI - A useful secondary alpha complementation screening procedure. PMID- 1515133 TI - Gel-loading dyes compatible with PCR. PMID- 1515134 TI - Simplified filter paper sandwich blot provides rapid, background-free northern blots. PMID- 1515135 TI - Simultaneous screening of colony blots with radioactive and non-isotopic probes. PMID- 1515136 TI - Identification of cis-diamminedichloroplatinum(II) adducts in DNA from drug treated human cell nuclei. PMID- 1515137 TI - Method for rapid, single reaction, direct screening of the delta F508 cystic fibrosis microdeletion. PMID- 1515138 TI - Molecular approaches for environmental monitoring of microorganisms. PMID- 1515139 TI - DH11S: an Escherichia coli strain for preparation of single-stranded DNA from phagemid vectors. AB - A new E. coli strain DH11S [mcrA delta(mrr-hsdRMS-mcrBC) delta(lac-proAB) delta(rec1398) deoR rpsL srl- thi-/F'proAB+ lacIqZ delta M 15] has been constructed. Transformation of DH11S competent cells with any of several different phagemid vectors [pSPORT1, pBluescript II SK(+), pGEM11Zf(+)] results in the production of highly purified single-stranded DNAs upon the addition of M13KO7 helper phage. Contamination by double-stranded DNAs was observed with all the other studied strains (XL1-Blue, JM109, DH5 alpha F'IQ). The optimal yield of single-stranded DNA production was obtained when glycerol stocks made from stationary phase cells or single colonies from overnight ampicillin plates of DH11S containing the phagemid vector were infected with M13KO7 helper phage using a wide range (1 to 100) of multiplicities of infection. Five different pSPORT1 clones containing cDNA inserts of various lengths (0.3 kb to 2.0 kb) were compared using these four different bacterial strains. The use of strain DH11S results in the best yields and quality of single-stranded DNA. Therefore, DH11S appears to be the best all-around host for various applications that require single-stranded DNA such as DNA sequencing, in vitro mutagenesis and construction of subtractive cDNA libraries. PMID- 1515140 TI - Producing a P1 bacteriophage library from pine: isolation and cloning of very high molecular weight DNA. AB - We have generated a genomic P1 bacteriophage library using Monterey pine (Pinus radiata) DNA. We first developed a method for isolating from pine tissue the very high molecular weight DNA necessary for the preparation of libraries requiring large inserts. The method involves protoplasting the cells, isolating nuclei and lysis in a high concentration of detergent. Fragments of greater than two megabases in size are produced in solution. Modifications introduced to the protocol for library preparation and for P1 plasmid isolation are described. PMID- 1515141 TI - Analysis of the T cell repertoire using the PCR and specific oligonucleotide primers. AB - Applications of PCR have revolutionized the field of immunogenetics particularly in studies of human leukocyte antigen class II polymorphism and more recently in the analysis of T cell receptor usage. The diversity of the variable region of the T cell receptor, however, has made it difficult to amplify the complete repertoire of T cell receptor transcripts. We have chosen to address this problem through the design of oligonucleotide primers specific for each of the known V alpha- and V beta-region T cell receptor families in order to characterize the T cell receptor repertoire. Using nonradioactive probes labeled with horse radish peroxidase, the system presented here allows for the rapid elucidation of the T cell receptor repertoire expressed in cells or tissue samples, such as those derived from autoimmune lesions. The identification of the T cell receptor repertoire involved in a pathogenic process can have therapeutic implications given the success of reversing experimental autoimmune disorders by directing specific forms of immunotherapy against V region gene products. PMID- 1515142 TI - Preparative peptide purification by cation-exchange and reversed-phase perfusion chromatography. AB - Cation exchange was compared to reversed-phase chromatography for the preparative purification of a 28-residue peptide (vasoactive intestinal polypeptide) on the 100-mg scale. Optimized high-speed, high-resolution methods were developed for both chromatographic modes on POROS Perfusion Chromatography flow-through particle chromatography columns. While both methods appeared to provide similar purity, the cation exchange column had approximately ten times the loading capacity per unit column volume as the reversed-phase column. Five-minute methods for desalting the cation exchange-purified peptide and analysis of fractions were developed using small reversed-phase columns. The cation-exchange method was scaled up to process 95 mg of crude peptide in a 12-min run. PMID- 1515143 TI - Improved chemiluminescent western blotting procedure. AB - A chemiluminescent Western blotting procedure and its application in assays for human transferrin and human immunodeficiency virus-I antibodies are described. The procedure is based on a chemiluminescent substrate, adamantyl 1,2-dioxetane aryl phosphate and alkaline phosphatase-labeled detection antibodies. Different membranes (polyvinylidene fluoride, nitrocellulose, nylon) and a proprietary membrane treatment agent (Nitro-Block) have been studied. This sensitive blotting procedure utilizing AMPPD, a polyclonal rabbit anti-transferrin:goat anti-rabbit IgG-alkaline phosphatase detection complex, and a PVDF membrane blocked with Nitro-Block permits the detection of 125 pg (1.6 fmol) of human transferrin. A novel 1,2-dioxetane substrate, CSPD, has also been evaluated. PMID- 1515144 TI - Changes in protein synthesis pattern during in vitro maturation of goat oocytes. AB - The regulation of meiotic events of goat oocytes from prophase I to metaphase II was studied by inhibiting protein synthesis at different times of the transition and by analyzing the changes in the protein synthesis pattern during maturation. Protein synthesis was required for germinal vesicle breakdown (GVBD). Nevertheless, the concomitant event to the rupture of germinal vesicle, i.e., chromosome condensation, took place even in a cycloheximide-containing medium. The transition from metaphase I to metaphase II was also protein synthesis dependent as evidenced by experiments using this protein synthesis inhibitor. The inhibition was partly reversible, i.e., after removal of the drug, oocytes were able to progress until metaphase I but could not proceed beyond this stage. Changes in the protein synthesis pattern were studied by radiolabelling of oocytes with [35S]methionine. These changes were correlated with the nuclear status of the oocyte: At GVBD, a polypeptide of 25 kD disappeared, while one of 27 kD appeared. At the same time, a polypeptide of 33 kD appeared, whereas concomitantly one of 34 kD became barely detectable and finally disappeared as the maturation progressed. During maturation, the synthesis of a 67 kD polypeptide increased and became predominant at the end of the maturation process. The synthesis of actin decreased after 18 hr of culture from a very high to a low level of synthesis. PMID- 1515145 TI - Role of a germ cell-specific sulfolipid-immobilizing protein (SLIP1) in mouse in vivo fertilization. AB - Sulfolipid-immobilizing protein 1 (SLIP1) is a germ cell plasma membrane protein that binds specifically to sulfogalactosylglycerolipid, a sulfoglycolipid found preferentially in mammalian male germ cells (Lingwood, Can. J. Biochem. Cell. Biol. 63:1077-1085, 1985b). SLIP1 in mouse and rat sperm exists on the periacrosomal membrane, where sperm initially bind to eggs. Using the in vitro mouse sperm-egg binding assay with in vitro-capacitated sperm, we obtained results previously suggesting that sperm SLIP1 is involved in mouse sperm-zona pellucida interaction. In this study, using the in vitro sperm-egg binding assay, we showed that SLIP1 in uterine sperm was similarly engaged in this process. Involvement of mouse sperm SLIP1 was also shown to be important in the in vivo fertilization process. Superovulated females inseminated with caudal epidididymal and vas deferens sperm preexposed to anti-SLIP1 IgG yielded only 20% fertilized zygotes, while 80% fertilization was observed in females inseminated with sperm preincubated with preimmune serum IgG. The lower fertilization rate was not due to changes in the sperm capacitation rate as assessed by chlortetracycline staining. PMID- 1515146 TI - Assessment of Pisum sativum agglutinin in identifying acrosomal damage in stallion spermatozoa. AB - The use of fluorescein-conjugated Pisum sativum agglutinin (FITC-PSA) was evaluated for its ability to distinguish acrosome-intact from acrosome-damaged stallion spermatozoa. Incubation of fresh (acrosome-intact) and frozen-thawed (acrosome-damaged) spermatozoa with FITC-PSA resulted in acrosome-intact spermatozoa that exhibited no fluorescence, while acrosome-damaged spermatozoa exhibited fluorescent staining over the rostral portion of the head and equatorial segment. Experiments using mixtures of various ratios of acrosome intact and acrosome-damaged spermatozoa determined the precision (intrasample coefficient of variation), and linearity (increased percentage of spermatozoa with PSA binding, with increased percentage of frozen-thawed spermatozoa in a sample) of FITC-PSA binding. The binding of FITC-PSA increased in samples as the portion of frozen-thawed (acrosome-damaged) to fresh (acrosome-intact) spermatozoa increased. A positive correlation existed (r = 0.98, P less than 0.05) between the percentage of FITC-PSA bound sperm and the proportion of damaged spermatozoa added to a sample. Location of PSA lectin binding on acrosome damaged spermatozoa, determined by electron microscopy using gold-conjugated PSA, was to components of the outer acrosomal membrane and acrosomal matrix. These results demonstrate that FITC-PSA binding may be useful in determining acrosomal integrity of fresh and frozen-thawed stallion spermatozoa. PMID- 1515147 TI - Release of tissue-type plasminogen activator by activated rat eggs and its possible role in the zona reaction. AB - The resumption of meiosis results in synthesis of tissue-type plasminogen activator (tPA) in the rat and mouse oocytes (Haurte et al., Cell 43:551-558, 1985). The present study demonstrates that freshly ovulated rat oocytes released their tPA into the surrounding medium upon in vitro activation by sperm penetration or treatment with a calcium ionophore. The presence of a neutralizing monoclonal anti-tPA antibody during in vitro activation by the calcium ionophore inhibited the activation-induced zona hardening and also preserved the ability of the oocyte to be penetrated by sperm subsequent to activation. Rat oocytes undergo zona hardening during in vitro maturation in the absence of serum, presumably as a result of spontaneous cortical granule release, based on findings in mice and hamsters. In the present study, the anti-tPA antibody prevented the zona hardening and enhanced partition by spermatozoa of rat oocytes that were matured in vitro without serum. Collectively, the observations reported have suggest a possible role of tPA released during the cortical granule reaction in the zona reaction, which contributes to the block to polyspermy. PMID- 1515148 TI - A transient rise in intracellular Ca2+ is a precursor reaction to the zona pellucida-induced acrosome reaction in mouse sperm and is blocked by the induced acrosome reaction inhibitor 3-quinuclidinyl benzilate. AB - The acrosome reaction induced by the zona pellucida in mouse sperm has been shown to proceed in two stages experimentally distinguishable by the fluorescent probe chlortetracycline. Entry into the first stage of sperm bound to isolated, structurally intact zonae pellucidae is blocked by the compound 3-quinuclidinyl benzilate. In this study, we show, utilizing the fluorescent Ca2+ indicator fluo 3, that the first stage of the zona-induced acrosome reaction is characterized by an increase in intracellular Ca2+, followed by a decrease as the acrosome reaction proceeds. This calcium transient is completely suppressed by 3 quinuclidinyl benzilate. We conclude that the Ca2+ transient is induced by the zona pellucida and is required for the zona-induced acrosome reaction. Blockage of this sperm intracellular Ca2+ transient provides a mechanism for the inhibitory action of 3-quinuclidinyl benzilate on the zona-induced acrosome reaction in mouse sperm. PMID- 1515149 TI - Natural degenerating mitochondria in ovarian follicles of a cyprinodontidae fish, Epiplatys spilargyreus (teleost). AB - This study examines the evolution of mitochondria in the follicular cells during the development of the ovarian follicle in the teleostean fish Epiplatys spilargyreus. The mitochondria are few in number until the end of previtellogenesis; their matrix is dense, and their cristae are well developed. They proliferate during vitellogenesis and then are modified by deterioration of their matrix. Multilamellar structures are organized in the vacuolized mitochondria. During postvitellogenesis, these modifications become more advanced. The mitochondria degenerate, leaving vacuoles that contain heterogeneous structures, which will be released into the intercellular spaces. At the end of these mitochondrial transformations, the follicular cells degenerate. They release the elements which will participate in forming the secondary envelope. PMID- 1515150 TI - Clusterin (SGP-2) in epididymal luminal fluid and its association with epididymal spermatozoa in androgen-deprived rats. AB - Clusterin is a heterodimeric glycoprotein synthesized and secreted by rat Sertoli cells and epididymal epithelium. The goal of this study was to determine the presence of clusterin in the luminal fluid of the cauda epididymides and its association with the membranes of developing spermatozoa in the presence and absence of androgen. We have previously demonstrated by two-dimensional (2-D) Western blot probing for clusterin that in epididymal fluid the amounts of clusterin were: caput greater than corpus greater than cauda. Luminal fluid from cauda epididymides was collected from control and orchiectomized rats (6 and 12 days) and orchiectomized animals that received testosterone implants. Equal volumes of fluid were analyzed by 2-D Western blot probing for clusterin. Following orchiectomy, there was an increase in clusterin in the luminal fluid after 6 days and maximal amount after 12 days compared with control cauda fluid. Orchiectomized animals which received testosterone treatment showed levels of clusterin comparable to that of controls. Serum clusterin was detected in fluid of orchiectomized animals with and without testosterone. Western blots of cauda sperm membrane extracts of control animals and orchiectomized animals treated with testosterone had a very low level of epididymal clusterin, whereas extracts collected from orchiectomized animals revealed high levels of clusterin. We suggest that, in the normal animal, clusterin is secreted into the lumen of the proximal epididymis where it binds to the sperm membrane. In the distal epididymis, clusterin dissociates from sperm and is processed (proteolysis/endocytosis). We hypothesize that, in the absence of androgen, the processing and regulation of clusterin is disrupted. PMID- 1515151 TI - Tight junctions and cavitation in the human pre-embryo. AB - In the human morula, tight junctions are found between all cell pairs, at all levels of cellular apposition, associated with underlying masses of microfilaments. In cavitating morula, lanthanum tracer gained access to the intracellular spaces, except at the intersections with nascent extracellular cavities, marking the first assembly of zonulae occludentes. Presumptive trophectoderm cells contained vacuoles and larger cavities often associated with secondary lysosome-like bodies. Since the vacuoles and intracellular and extracellular cavities contain electron-dense polygranules of about 23 nm diameter, they may have common origins. In trophectoderm cells of the early blastocytes, the large intracellular vacuoles and cavities were absent, and the zonulae occludentes were located apically. Mechanisms for nascent blastocoele formation are discussed. PMID- 1515152 TI - Intracellular Ca2+ response of rabbit oocytes to electrical stimulation. AB - Electrical stimulation is known to cause activation in mammalian oocytes, possibly by eliciting an elevation in intracellular calcium (Ca2+). This study reports intracellular Ca2+ concentrations in mature rabbit oocytes using the Ca2+ indicator fura-2. Calcium levels were determined prior to, during, and after the administration of an electrical pulse (3.6 kV/cm for 60 microseconds). Baseline Ca2+ levels ranged from 30 to 90 nM. The intracellular Ca2+ transient evoked by a pulse, peaked at 11 sec, was highly variable in amplitude (40-300 nM) and returned to prepulse levels within 300 sec. Electrically stimulated oocytes did not exhibit repetitive Ca2+ transients. The size of the cytoplasmic Ca2+ rise was influenced by the duration of the pulse, the field strength and the concentrations of external Ca2+ rise was influenced by the duration of the pulse, the field strength and the concentrations of external Ca2+ (P less than 0.05). Oocytes electrically stimulated in the presence of 100 microM CaCl2, which evoked Ca2+ transients with a mean magnitude of 120 nM, activated at a higher rate (P less than 0.05) than oocytes stimulated in the presence of either higher or lower levels of external Ca2+. Although oocytes electrically shocked at 16-18 hr after administration of human chorionic gonadotropin (hphCG) activated at a lower rate than oocytes stimulated at 22-24 hphCG (P less than 0.05), their intracellular Ca2+ response to the pulse was similar (P less than 0.05). These results indicate that electrical pulse parameters and extracellular Ca2+ concentrations can be used to modulate intracellular Ca2+ levels and optimize oocyte activation rates.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1515153 TI - Murine monoclonal antibodies against staphylococcal enterotoxin B: production and characterization. AB - A group of 14 monoclonal antibodies (mAbs) to staphylococcal enterotoxin B (SEB) were obtained by fusion of Sp2/O myeloma cells with spleen cells from female BALB/c mice immunized with commercial SEB. The antibodies belonged to IgG1 and IgG2b subclasses. We evaluated the anti-SEB titres, competition assays and sensitivity of detection by indirect ELISA. Reactivity and cross-reactivity were also studied by indirect ELISA and confirmed by immunoblotting. All the mAbs reacted with SEB and with a second band which had a different electrophoretic mobility and probably represents an aggregate of SEB or SEB bound to membranes. Three mAbs reacted only with SEB and the rest showed cross-reactions with SEC1. No reactions were observed against any other serovar (SEA, SED and SEE) or other proteins. PMID- 1515154 TI - Susceptibility of isolates of Acinetobacter anitratus and Acinetobacter lwoffii to the bactericidal activity of normal human serum. AB - The bactericidal activity of normal human serum against the Gram-negative coccobacilli Acinetobacter anitratus and Acinetobacter lwoffii was studied; 12% and 84%, respectively, of the tested strains appeared to be sensitive. Thus, serum resistance may be an important factor contributing to the pathogenic potential of A. anitratus strains. Three types of bactericidal action were shown. In the first, the strains were killed when the alternative complement pathway was activated. In the second, some strains required both the classical and alternative pathways. In the third variant, the strains needed either the alternative or classical activation pathway. PMID- 1515155 TI - Antibodies to outer membrane proteins of Vibrio cholerae induce protection by inhibition of intestinal colonization of vibrios. AB - An antiserum was raised against the outer membrane (OM) preparation of a Vibrio cholerae 01 strain (Classical, Ogawa) and rendered specific for the outer membrane proteins (OMPs) by absorption with its lipopolysaccharide (LPS). The anti-OMP serum showed reactivity against OM preparations of other 01 and non-01 V. cholerae strains in enzyme-linked immunosorbent assay. The antiserum also induced significant protection against V. cholerae challenge in the suckling mouse model. This protection was found to be independent of biotype, serotype as well as serovar of the challenge organism and was demonstrable even at subagglutinating dilutions of antiserum. The Fab (IgG) fragment, prepared from the anti-OMP serum, also induced passive protection in similar experiments. Further studies demonstrated that the anti-OMP serum as well as its Fab (IgG) fragment markedly inhibited the intestinal colonization of a highly colonizing V. cholerae 01 strain A17 (El Tor, Ogawa). These results highlight the importance of V. cholerae OMPs in immunoprophylaxis against cholera. PMID- 1515156 TI - Intracellular growth of Mycobacterium avium in human macrophages is linked to the increased synthesis of prostaglandin E2 and inhibition of the phagosome-lysosome fusions. AB - A virulent strain of Mycobacterium avium grew actively inside human adherent peripheral blood monocyte-derived macrophages. Bacteria were always confined to the phagosome compartment and were encapsulated. Cytochemical labeling of acid phosphatase using transmission electron microscopy showed a strong inhibition of the phagosome-lysosome fusions (PLF) in macrophages as not more than 25-30% bacteria containing phagosome at any time effectively fused with lysosomes. In case of a positive fusion event, the bacterial capsule prevented the diffusion of the lysosomal contents to the bacterial surface. Moreover, the infection of macrophages both by living and gamma-killed M. avium was linked to an increased synthesis of prostaglandin E2 (PGE2); however the total amount of PGE2 synthesized in the latter case was significantly lower than that observed with viable organisms. Our results suggest that the inability of human macrophages to control M. avium infection is linked to immunosuppressive pathways, e.g. enhanced synthesis of PGE2 and also to an impairment of normal microbicidal functions of the infected macrophages. PMID- 1515158 TI - Immunodominant antigens recognized by the human immune response to infection by organisms of the species Leptospira interrogans serogroup Australis. AB - Serum samples from patients infected by organisms of Leptospira interrogans serogroup Australis were tested by Western blot to determine the nature of major antigens that are involved in the immune response. Although there was some patient-to-patient variability, immunodominant genus-specific antigens were found to be proteins of apparent molecular ratio 68, 46 and 35-kDa, and lipopolysaccharide (LPS) sub-units in the 35-14-kDa region. Serogroup epitopes specific for Australis were exclusively saccharides of about 32 and 24 kDa: a serovar-specific antigen for serovar lora was of 38-40 kDa and behaved like a protein. Antibodies to the LPS serogroup-specific antigens and to the 38-40 kDa protein were long-lasting and consequently suggest that these immunodominant epitopes are important in resistance to re-infection. PMID- 1515157 TI - Effect of indomethacin on the modulation of Mycobacterium avium growth in human macrophages by interferon gamma, retinoic acid and 1,25(OH)2-vitamin D3. AB - A virulent strain of Mycobacterium avium was grown actively inside human adherent peripheral blood monocyte-derived macrophages with enhanced synthesis of prostaglandin E2 (PGE2). We therefore decided to investigate if the inability of human macrophages to control M. avium infection could be reversed using various immunomodulators, i.e. retinoic acid (RA), 1,25 dihydroxyvitamin D3 (D3) and interferon gamma (IFN gamma) alone or in combination, and whether this reversal was further potentiated by the addition of indomethacin (IND), a potent inhibitor of PGE2 biosynthesis. Among the various immunomodulators employed, only RA alone or in association with D3 or both D3 and IFN gamma were able to induce a clear mycobacteriostatic effect, which was further potentiated by IND. Our data suggest that immunosuppressive pathways induced in macrophages infected by M. avium result partly from an increased synthesis of PGE2 occurring soon after infection. PMID- 1515159 TI - Intestinal, segmented, filamentous bacteria. AB - Segmented, filamentous bacteria (SFBs) are autochthonous, apathogenic bacteria, occurring in the ileum of mice and rats. Although the application of formal taxonomic criteria is impossible due to the lack of an in vitro technique to culture SFBs, microbes with a similar morphology, found in the intestine of a wide range of vertebrate and invertebrate host species, are considered to be related. SFBs are firmly attached to the epithelial cells of the distal ileal mucosa, their preferential ecological niche being the epithelium covering the Peyer's patches. Electron microscopic studies have demonstrated a considerable morphological diversity of SFBs, which may relate to different stages of a life cycle. Determinants of SFB colonization in vivo are host species, genotypical and phenotypical characteristics of the host, diet composition, environmental stress and antimicrobial drugs. SFBs can survive in vitro incubation, but do not multiply. On the basis of their apathogenic character and intimate relationship with the host, it is suggested that SFBs contribute to development and/or maintenance of host resistance to enteropathogens. PMID- 1515160 TI - On the relative importance of specific and non-specific approaches to oral microbial adhesion. AB - In this paper, it is suggested that specificity and non-specificity in (oral) microbial adhesion are different expressions for the same phenomena. It is argued that the same basic, physicochemical forces are responsible for so-called 'non specific' and 'specific' binding and that from a physico-chemical point of view the distinction between the two is an artificial one. Non-specific interactions arise from Van der Waals and electrostatic forces and hydrogen bonding, and originate from the entire cell. A specific bond consists of a combination of the same type of Van der Waals and electrostatic forces and hydrogen bonding, now originating from highly localized chemical groups, which together form a stereochemical combination. The absence or presence of specific receptor sites on microbial cell surfaces must therefore be reflected in the overall, non-specific surface properties of cells as well. This point is illustrated by showing that glucan-binding lectins on mutans streptococcal strains may determine the pH dependence of the zeta potentials of these cells. When studying microbial adhesion, a non-specific approach may be better suited to explain adhesion to inert substrata, whereas a specific approach may be preferred in case of adhesion to adsorbed protein films. Adhesion is, however, not as important in plaque formation in the human oral cavity as is retention, because low shear force periods, during which adhesion presumably occurs, are followed by high shear force periods, during which adhering cells must withstand these detachment forces. Evidence is provided that such detachment will be through cohesive failure in the pellicle mass, the properties of which are conditioned by the overall, non-specific substratum properties. Therefore, in vivo plaque formation may be more readily explained by a non-specific approach. PMID- 1515161 TI - Genetics and molecular biology of methanotrophs. AB - Over the last 20 years or so, the obligate methane-oxidizing bacteria (methanotrophs) have attracted considerable interest. As they grow on a relatively cheap and abundant carbon source, they appeared ideal organisms for the production of bulk chemicals, single-cell protein and for use in biotransformations. More recently their cooxidation properties have been investigated for bioremediation, including the removal of chlorinated compounds such as trichloroethylene from polluted groundwaters. These studies have resulted in a great deal of information on the physiology and biochemistry of methanotrophs but sadly the molecular biology and genetic studies of these organisms have lagged behind. This has been in part due to the obligate nature of the methanotrophs and the refractory nature of such organisms to conventional genetic analysis. However, the more recent availability of broad-host range plasmids coupled with improvements in molecular biology methods have allowed the development of molecular genetic techniques for methanotrophs. The purpose of this review is to summarize what is known about the genetics and molecular biology of methanotrophs and how this information can be used to complement previous and current biochemical studies on the unique property of these bacteria, i.e. the ability to oxidize methane to methanol. Recent developments in molecular ecology techniques that may be applied to these apparently ubiquitous organism are also considered. PMID- 1515162 TI - Enzymes and pathways of polyamine breakdown in microorganisms. AB - The information currently available on the breakdown of spermidine and putrescine by microorganisms is reviewed. Two major metabolic routes have been described, one for the free bases via delta 1-pyrroline (4-aminobutyraldehyde), the other via N-acetyl derivatives. In both pathways oxidases or aminotransferases are the key enzymes in removing the nitrogen atoms. The two routes converge at 4 aminobutyrate, which is then metabolized via succinate. The degradation of putrescine in Escherichia coli has been well characterized at both genetic and biochemical levels, but for other bacteria much less information is available. The C3 moiety of spermidine is broken down via beta-alanine, but the metabolism of this compound and its precursors is poorly understood. In yeasts, a catabolic route for spermidine and putrescine via N-acetyl derivatives has been described in Candida boidinii, and the evidence for its occurrence in other species is reviewed. Except for the terminal step of this pathway, the same group of enzymes can metabolize both the C3 and C4 moieties of spermidine. It is likely that other routes of polyamine catabolism also exist in both bacteria and yeasts. PMID- 1515163 TI - Children fathered by men treated for testicular cancer conceived before, during and after chemotherapy--examination for evidence of congenital malformations, malignancies and immunological defects. AB - Hundred children of 64 fathers with testicular tumour treated from 1979 on at the National Institute of Oncology, Budapest were studied. Three groups were formed on the basis of the time of conception. 59 children were born before the illness of the fathers, 19 during the 9 pretreatment months and 22 during or after combined chemotherapy. Family anamnesis, perinatal and gestational data were listed, thereafter physical, laboratory, immunological, psychiatric, and, if required, radiological examinations were made. No difference was detectable in the somatic and psychiatric status of the three groups, development was well balanced, corresponding to age. Protocols of the combined chemotherapy applied and incidence of anomalies, malformations, malignancies and other diseases were recorded. Their incidence was similar in all three groups though frequently this was higher than that of the normal population. Often cumulated incidence of severe congenital malformations was found in the group conceived after concluded therapy where twice as many girls were born as boys. The interval between conception and the end of therapy was established in the case of children conceived during and after therapy. This was shortest in the case of healthy children, the number of healthy children conceived during cytostatic treatment was also remarkable. Further compilation of data and individual evaluation of case reports is recommended. PMID- 1515164 TI - A new chromosomal translocation t/1;22/ /q25;q12/ in a 17-month-old girl. PMID- 1515165 TI - Prognostic data of the second follow-up in childhood wheezy bronchitis. AB - 206 non-selected children who had wheezy bronchitis before two years of age were observed in the first follow-up (1985) about 9 years after their clinical wheezy episode. Among them 31 patients (15%) showed bronchial hyperreactivity (B.H.) after acetylcholine challenge and 9 children became asthmatic. In the second follow-up (1988) 28 children who had B.H. and randomly 17 children who did not have B.H. participated. The prognosis of wheezy bronchitis is good, there was no new asthmatic child at this time. The B.H. was found to diminish only in 7 cases. During the last 3 years wheezy episodes developed only in 5 asthmatic patients. The skin prick test (SPT) positivity did not change (26% versus 29%). The familial atopy in the group B.H. is higher (43%) than in the group non B.H. (23%) but the difference is not significant (X2 = 1.72). No significant correlation was found between the familial atopy and SPT positivity. The familial smoking is higher in the group B.H. (78% versus 64%) but no significant influence on the B.H. (X2 = 1.03) could be detected. PMID- 1515166 TI - Monitoring the therapy of acute lymphoid leukemia (ALL) in children--changes induced in clinical, cytological and immunological parameters during treatment of high malignancy ALL with ALL-BFM 88. AB - The ALL-BFM 88 RF greater than 1.7 treatment of high malignancy ALL patients in remission was monitored at the 4th week of Protocol I. The qualitative and quantitative processing of parameters indicating cellular transformations by light and electronmicroscopy was performed in lymphocytes separated from peripheral blood drawn at scheduled times of therapy. The immunophenotype of sample lymphocytes was determined by indirect immunofluorescent techniques, by listing the percentual level of CD2, CD3, CD4, CD8, CD19 surface antigens. The incidence of infections, confirmed clinically and bacteriologically, was recorded. The parameters of the patients were compared to those of healthy children. In the group of patients with high malignancy in the intensive period of ALL-BFM 88 RF greater than 1.7 therapy the incidence of cells rich in organelles, dense granules and vacuoles was significantly (p less than 0.05) higher compared to the control cells, poor in structures. During the weeks of induction and after the consolidating combination with VM-26+ARA-C the expression of surface antigens of the lymphocytes was reduced. That means that up to the introduction of maintenance treatment the presence of surface antigens remained below the range of normal deviation. These data obtained during monitoring revealed that the morphological and functional integrity of cells was damaged in patients with high malignancy ALL during intensive therapy, though only temporarily. PMID- 1515167 TI - Diagnostic value of clinical features and supplementary investigations in tuberous sclerosis in children. AB - The author evaluates the usefulness of clinical features and some supplementary investigations in diagnosis of tuberous sclerosis in children. 52 children ranging in age from 1 month to 14 years took part in the study. Usually depigmented naevi were the first sign of tuberous sclerosis and were seen in 98% of affected children. Epileptic seizures occurred in 96% of patients, mostly during the first year of life. Axial computed tomography of brain seems to be very helpful in diagnosis of tuberous sclerosis in every age. Multiple periventricular calcifications were found in 98% of children. Two-dimensional echocardiography was especially useful in infants and children below 2 years of age. Retinal hamartomas were found in 25% of children with tuberous sclerosis. In some cases these changes were revealed during the first year of age. Abnormal EEGs were found in 90% of recordings. The EEGs tended to improve with increasing age. In 25% of children one of parents was affected by tuberous sclerosis. The careful skin examination of both parents can be especially helpful in children with doubtful diagnosis of tuberous sclerosis. PMID- 1515168 TI - Role of mitochondria in oncogenesis. PMID- 1515169 TI - Insulin, growth factors, and cancer cell energy metabolism: an hypothesis on oncogene action. AB - The hexokinase-mitochondrial acceptor theory provides a model of insulin action which unifies the metabolic effects of this hormone and suggests that these result from insulin's stimulatory effect on mitochondrial ATP synthesis. There are similarities between these changes in cells exposed to insulin and in mitochondria of transformed cell lines and cancer cells, where an increased binding of hexokinase to mitochondria is observed. This phenomenon may play a key role in the high rates of glycolysis sustained by cancer cells under aerobic conditions. Structural and functional evidence support the hypothesis that certain growth factors and oncogenes act through stimulation of oxidative phosphorylation via promoting HK binding to mitochondria. PMID- 1515170 TI - A sensitive radioisotopic assay of myo-inositol: its application to rat pancreatic islets. AB - A radioisotopic procedure for the assay of myo-inositol is presented. It is based on the generation of NADH from NAD+ in the reaction catalyzed by myo-inositol dehydrogenase and the subsequent NADH-dependent conversion of 2-[U 14C]ketoglutarate to 14C-labeled L-glutamate in the reaction catalyzed by glutamate dehydrogenase. This method was applied to the measurement of myo inositol in rat pancreatic islets. The myo-inositol islet content was decreased when the animals were fed a diet deprived of myo-inositol. When incubated in the absence of exogenous D-glucose, pancreatic islets, like parotid cells, released myo-inositol in the incubation medium. Over 90 min of incubation, a rise in extracellular D-glucose concentration increased the myo-inositol islet content, which was decreased, however, after incubation in the presence of carbamylcholine. These findings indicate that the myo-inositol content of islets is affected by nutritional and other environmental factors. PMID- 1515171 TI - Effect of chronic metformin treatment of hepatic and muscle glycogen metabolism in KK mice. AB - Noninsulin-dependent diabetic KK mice, aged 90-100 days, with hyperinsulinemia and insulin resistance were treated with either metformin (N = 13) or water (control, N = 10) orally at a concentration of 50 mg/kg twice daily for 28 weeks. Age-matched nondiabetic Swiss Webster (SW) mice were also similarly treated. Liver and skeletal muscle glycogen synthase and phosphorylase enzymes were determined in all groups of mice. Both enzymes were significantly lower in control KK than in control SW mice. Metformin did not influence either of these enzymes in nondiabetic SW mice. However, it significantly increased the active form of glycogen synthase (a form) in both the liver and muscle of KK mice. Metformin also increased the active form of phosphorylase (a form) in the liver but not in the muscle of these mice. Hepatic glycogen content was similar in both control and metformin-treated KK mice. However, the muscle glycogen content was significantly higher in metformin-treated than in control KK mice. These data suggest that metformin preferentially stimulates glycogen synthesis in skeletal muscle, and this seems to be responsible for the observed improvement in fasting glucose and glucose response to an oral glucose load in KK mice. PMID- 1515172 TI - The measurement of mitochondrial beta-oxidation by release of 3H2O from [9,10 3H]hexadecanoate: application to skeletal muscle and the use of inhibitors as models of metabolic disease. AB - We describe the use of a simple assay for beta-oxidation which depends on the release of 3H2O from [9,10-3H]hexadecanoate. This was compared with the use of [1 14C]hexadecanoate which gave comparable results when all the products of beta oxidation were measured. The prediction that 75% of the tritium is released as 3H2O and 25% as [2-3H]acetyl units was confirmed. The assay was used successfully to demonstrate impaired beta-oxidation in tissue preparations from rats treated with etomoxir and methylenecyclopropylpyruvate which are known inhibitors of beta oxidation. Abnormalities of beta-oxidation were also detected in skeletal muscle from patients with defects of mitochondrial oxidation. PMID- 1515173 TI - Blood isoprene concentrations in humans and in some animal species. AB - The concentrations of isoprene, the main hydrocarbon of human breath, were measured in the blood of humans and of different animal species (rat, rabbit, dog, ewe, cow). In human blood, the concentrations of isoprene were between 15 and 70 nmol/liter (mean value of 37 +/- 25 (SD) nmol/liter). In the blood of the different animal species tested, traces of isoprene were unambiguously detected by mass spectrometry, but the levels were always lower than 1 nmol/liter. PMID- 1515174 TI - Abnormal insulin receptor binding in cultured monocytes in myotonic muscular dystrophy. AB - Even though one of the characteristic features of myotonic dystrophy (MyD) is the high level of circulating insulin, 125I-insulin-binding data in MyD have been controversial. In the present study we utilized cultured monocytes to avoid problems of reproducibility and variability in age, and examined the affinity and binding characteristics of 125I-insulin binding in MyD patients and controls. The Bmax and mean affinity constant, Ka, were significantly lower, while the number of receptors per cell had increased in the patient group as compared to the controls. The data confirm our earlier findings that there is no primary defect in insulin receptors in MyD, and the disturbed insulin response may be due to an abnormality in the membrane environment. Since the insulin receptor is an integral membrane protein, abnormal plasma membrane lipid composition may lead to impaired lipid-protein interactions, and hence affect the binding characteristics in MyD. PMID- 1515175 TI - Ca(2+)-ionophore A23187 and the Ca(2+)-mobilizing hormones serotonin, vasopressin, and bradykinin increase mitochondrially bound hexokinase in muscle. AB - We show that a rise in cytosolic-free Ca2+ in muscle, induced by Ca(2+)-ionophore A23187 or by the Ca(2+)-mobilizing hormones serotonin, vasopressin, and bradykinin, increases the binding of hexokinase to mitochondria in muscle. This increase could be prevented by treatment with the calmodulin antagonists trifluoperazine or CGS 9343B (a novel, potent, and selective inhibitor of calmodulin activity) which strongly suggests that calmodulin is involved in the Ca(2+)-induced binding of the enzyme to muscle mitochondria. PMID- 1515176 TI - Enzyme-linked immunoassay of haptocorrin: analysis of milk and granulocytes. AB - An enzyme-linked, sandwich-type immunoassay method was described for quantitive assay of haptocorrin. The ranges of haptocorrin concentrations measurable by the method were comparable with those by radioimmunoassay. Using the method, the mean +/- SD of haptocorrin was 4.83 +/- 1.23 micrograms/ml in the colostrum (4th and 5th days after parturition), 3.17 +/- 1.77 micrograms/ml in the mature milk, and 21 ng/10(4) granulocytes (634 ng/mg protein). Haptocorrin from milk showed a homogeneous band at 66 kDa on SDS polyacrylamide electrophoresis followed by immunoblotting, while that from the granulocytes exhibited several closely aligned bands at 80 kDa and one or two bands at around 20 kDa. PMID- 1515178 TI - [CT in the study of laryngeal carcinoma]. AB - The advances in conservative surgery regarding larynx carcinoma makes necessary nowadays a more precise staging than was required before. In this work we describe our experience with the 54 cases which were studied in our center from March 1988 until October 1990. The radiological findings using CT were correlated with those by clinical exploration and checked by pathology in all cases. PMID- 1515177 TI - Detection of molecular deletions in the Chinese DMD patients using two amplified dystrophin sequences. AB - This Brief Communication reports the detection of molecular deletions in Chinese DMD patients using two new amplified dystrophin DNAs involving the regions of exon 49 and 50. The results show that over 50% of the DMD deletions can be rapidly detected by PCR amplification of these two dystrophin sequences. PMID- 1515179 TI - [Contribution of clinical and diagnostic aspects of vocal cord nodules, polyps, and Reinke's edemas]. AB - We have made a retrospective study about 100 cases of vocal cords nodules, polyps and polypoid degeneration: we study the clinic and diagnostic aspects for this pathology that has been considered of functional cause. We also have made a review of literature. PMID- 1515180 TI - [Prognostic value of lymph node histologic pattern in epidermoid carcinoma of the larynx]. AB - Histologic specimens from 48 patients with squamous cell carcinoma of the larynx treated exclusively by surgery were studied with special attention paid to the reactivity of regional lymph nodes. The lymph nodes were classified into four microscopic patterns of immune response: lymphocytic predominance, sinus histiocytosis, germinal center predominance and unstimulated or lymphocytic depletion. As a result no correlation were then made between the patterns and survival rate at 5 year follow-up. PMID- 1515181 TI - [Value of myotomy of the lower constrictor in surgery of tracheo-esophageal puncture]. AB - The importance of the inferior myotomy for speech restoration in total laryngectomized patients following not only primary techniques (speech restoration by tracheo-esophageal puncture during total laryngectomy) but also secondary punctures, is well documented. In this paper, the results obtained by manometric studies applied to 25 patients divided into two groups are shown (the first group) (15 patients) following primary techniques, and the second one (10 patients) following secondary punctures. We observe a sphincter pressure decreasing after secondary myotomy in those patients which previously presented dysphagia, prostheses breaking or intermittent speech, therefore considering the inferior constrictor myotomy as of great value in speech rehabilitation. PMID- 1515182 TI - [Diminution of epidermal growth factor in saliva of patients with carcinoma of the oropharynx]. AB - EGF, the Epidermal Growth Factor which is found ubiquitous in the human body can also be detected in saliva and increases in general proliferation and differentiation of epithelial cells which enables mucosa regeneration to maintain their protective function. In this study concentrations of EGF in saliva of smokers and patients with carcinoma of the oropharynx were examined. Both groups showed a decreased concentration compared to non smokers. We studied also secretion of EGF in saliva after smoking. Only the group of non smokers showed a transient elevation of EGF. PMID- 1515183 TI - [Post-surgical results of 48 septal perforations]. AB - We have studied the post-surgical results of 48 perforations of the nasal septum, regarding their etiology, location and size, which must be taken into account when deciding which closure technique to use. PMID- 1515184 TI - [Acute external otitis: retrospective study of 170 cases]. AB - 170 external otitis have been diagnosed and treated for one year (1989) in our ENT department. The etiology of the otitis was both bacterial and mycotic. The purpose of this paper is to study the clinical, therapeutic, epidemiologic and microbiologic aspects of this type of otitis. PMID- 1515185 TI - [Calcium phosphates in otologic surgery. III. The role of fibrin glue in the integration of calcium phosphate implants. Experimental study]. AB - Obliteration of the mastoid cavity has been realized with calcium phosphates associated to heterologous fibrin glue in otologic surgery. 22 artificially created epitympanic and 65 femoral defects in 22 rabbits were closed by means of dense or porous granulates of hydroxyapatite with homologous fibrin glue. Follow up was for three weeks to 6 months. Osteo-integration of the implants was significantly delayed in the first weeks, comparing the integration of the same phosphates without fibrin glue. PMID- 1515186 TI - [Audiometric value of workers exposed to different levels of occupational noise]. AB - We have obtained the information collected in routine clinical examinations of 806 healthy workers. We have studied the threshold hearing levels (audiometries) of our sample. Workers have been classified under three groups of noise exposure- low, medium and high--according with their job and with the activity of the company where they work. We have take into account the influence of factors such as age, use of ototoxic substances (certain antibiotics, tabac, alcohol) or presence of otoscopic irregularities which can affect the hearing levels. In general, hearing losses increase with noise exposure in all the explored frequencies; in the other hand, in the three groups of noise exposure the highest loss is for the 4000 Hz frequency. Losses in left hear are systematically higher than in right hear. PMID- 1515187 TI - [Influence of acoustic stimulation in the maturation of the auditory pathway]. AB - The aim of this study is to analyze the relationship between age and the maturational changes occurring in the peripherical auditory system and the influence of the acoustic stimulation. With this purpose Auditory Brainstem Responses (ABR) were recorded at the 35 and 39 weeks gestational age, in 56 ears of 28 premature infants. The ABR were analyzed the changes in latency values of the I, V waves and I-V intervals. In order to know the influence of the acoustic stimulation on the development of auditory pathway, we made 2 groups with the 28 premature children, one of them control group and the other stimulated with maternal voice from 35 till 39 weeks. The stimulated group had one maturate auditory evoked responses at 39 weeks gestational age. Showing a latency decrease wave V and I-V interval, compared to control group. PMID- 1515188 TI - [Surgical treatment of Eagle syndrome by way of the oropharynx. A case report]. AB - The authors present one case of elongated Styloid process which surgeons was undertaken due to intense symptomatology. Oropharyngeal approach was used and showed to be the election way for resection. PMID- 1515189 TI - [Adverse reactions to medications in patients in ambulatory otorhinolaryngology]. AB - A 12 months prospective study to detect adverse drug reactions (ADR) was carried out in an ORL outpatients clinic. 52 patients (1.8%) out of 2891 examined suffered one or more ADRs. The incidence was higher in women and in older patients. 94% of the ADRs were mild to moderate and 3 patients suffered irreversible lesions. Reactions were most commonly located in the nervous system (50%) and gastrointestinal tract (21%). The most common drugs involved were cardiovascular (40%) and central nervous system (25%) active drugs. Papers concerning ADRs published from 1976 to 1985 in spanish otorhinolaringologic journals have also been analyzed. 0.88% of 1357 published papers described ADRs. The incidence of ADRs observed in our study is higher than expected from the low number of papers published on this subject. PMID- 1515191 TI - Public health medicine. PMID- 1515190 TI - [Infraorbital bone hemangioma]. AB - Osseus hemangioma is a rare tumor. Its concept and a etiology are not well established. We preset a review and a case of this tumor located in the upper maxilla. Clinical, of this exploration and pathology are studied in this paper. Antigen in factor VIII has been observed. Considerations on different diagnosis are made. PMID- 1515192 TI - Race and ethnicity in health research. AB - 'Race' and 'ethnicity' are increasingly being used as variables in health research. However, studies have been mainly descriptive and have not been used to develop and evaluate strategies to improve health care. In part this reflects the poor analytical standards. The status of the concepts of 'race' and 'ethnicity' as research tools are rarely considered and there is poor consistency in terminology. This paper gives an overview of the research literature and raises questions about the validity of 'race' and 'ethnicity' as epidemiological variables. The tendency to collect routine ethnic data and include ethnic variables in an ad hoc and uncritical way in the United Kingdom and other countries may help transform minorities into mere statistical categories and produce data and findings which reinforce stereotypes. Multiculturalist ethnic health explanations also tend to displace more material explanations of health outcomes. It is concluded that more thought and care is needed before data are routinely categorized by ethnicity, or race or ethnicity are included as variables in research. PMID- 1515193 TI - Selective medical examination at school entry: should we do it, and if so how? AB - A prospective study was conducted on 82 consecutive 5+ examinations performed by four school doctors over a period of two months. The aim was to assess the impact of applying selection criteria for examination. Information gathered included immunization status, history of previous developmental assessments and previous detection of problems, and the result of the examination for each child. Forty three per cent of children were up to date with their immunizations, 66 per cent had had a six-week check and 38 per cent and 17 per cent had been assessed at 15 months and 2 1/2 years respectively. Forty-eight problems were detected in 37 children (45 per cent), of which 27 had not been previously detected. Of these, 19 were detected by the school nurse before the examination as a result of hearing (nine) and vision (10) testing and measurement of height and weight (one). Of the remaining problems, four were presented by the parent, one by the teacher and two were detected by the school doctor. If a policy of selective examination had been in place in which children were called for examination only if they had never been assessed before, or where there were no records of a previous assessment, or if their immunizations were incomplete, or they had previous problems, or the school nurse or teacher or parent had expressed concern, all but four children would have been examined. It was concluded that this particular method of selection would be unproductive and that a system whereby the school nurse was responsible for screening and selection for examination would be preferable.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1515194 TI - Rationality and the use of formulae in the allocation of resources to health care. AB - The paper describes how the apparent move towards rationality in allocating resources in the National Health Service using statistically based formulae is illusory. This is not just a technical problem of poor application of statistical techniques. The basic problem is to find a combination of factors reflecting dimensions of need and then appropriate weights with which to combine them within the context of the guiding principles of equity and efficiency. The paper explains how there has been little consistency in measuring need and how statistical methods have often masked the lack of appropriate data and models. Alternative approaches to measuring need within a policy context are discussed and a research agenda is outlined which, rather than concentrating on evermore complex statistical techniques, focuses on the necessity for more validly operationalizing 'needs' and their resource implications. PMID- 1515195 TI - Cost of neonatal care across a regional health authority. PMID- 1515196 TI - Non-consulters and high consulters in general practice: cardio-respiratory health and risk factors. AB - The 1990 General Practitioner contract requires that health promotion and illness prevention services should be provided to all patients aged 16-74 years. Consultation rates over a period of three years were examined in 7010 middle-aged men in Great Britain to compare the cardio-respiratory health and risk factor status of non-consulters (men who did not consult in three years) with those of average consulters (men who consulted 3-5 times in three years) and high consulters (men who consulted 24 or more times in three years) to assess their relative need for health promotion and illness prevention services. The non consulters (n = 1025) were remarkably similar to the average consulters (n = 1585) in health and lifestyle characteristics. The high consulters (n = 306) had a greater burden of ill-health and a less healthy lifestyle. Chest pain on exertion, chronic bronchitis, breathlessness or wheeze were present in 23 per cent of non-consulters, 27 per cent of average consulters and over 50 per cent of high consulters. Similarly, 48 per cent of the non-consulters smoked, drank heavily or were obese compared with 47 per cent of the average consulters and 61 per cent of the high consulters. The prevalence of recall of high blood pressure which had been diagnosed by a doctor rose from 6 per cent in non-consulters and 10 per cent in average consulters to 29 per cent in high consulters.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1515197 TI - Use of cancer surveillance data for comparative analyses. PMID- 1515198 TI - Unexpected high mortality rates found in a review of district statistics: what action is appropriate? AB - The regular review of statistical and other data is now a routine public health activity in district health authorities. The interpretation of findings indicative of high or otherwise unexpected rates of mortality or disease may be complicated by small numbers, and also by questions concerning the reliability with which the available data describe the problems. Judgement about whether to undertake further investigation of these problems is subject to uncertainty about the likely effectiveness and efficiency of the investigation, and of any remedial action that would be expected to follow. Examples of these problems are explored in relation to the finding of a high rate of infant and late neonatal mortality in a district population, and a high rate of female suicide. The late neonatal death rate showed a rising trend over a period of four years and was significantly elevated above national and regional rates. The perinatal death rate was not correspondingly low, nor had there been an excess of multiple births over the period. A review of neonatal death certificates did not demonstrate any identifiable problems relating to either the cause or place of death, and the high rate subsequently reverted to the expected level without further intervention. In the case of female suicide, analyses including deaths by misadventure and open verdicts were carried out to allow for possible differences between men and women in the certification of suicide. However, this did not alter the conclusions, and further investigation of the circumstances of death is planned to assess the potential for preventive action in the locality.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1515199 TI - Criteria for audit of annual reports on the public health: do they exist? AB - Production of an annual report is a statutory duty of the Director of Public Health; its production uses significant resources. Audit of reports may help in the effective use of these resources. For audit to be performed criteria need to be agreed upon which to set standards. The present study investigated whether Directors of Public Health agree on suitable criteria for the audit of annual health reports. Districts within North East Thames Regional Health Authority were paired; Directors of Public Health, who had produced the most recent report, interviewed each other using a semi-structured questionnaire. Reports were examined for the presence of the 'key indicators' from the common data set. The results show that there was little agreement on what were suitable criteria to evaluate reports. The criteria in the Toolbox produced by the Faculty of Public Health Medicine were thought to be unsuitable because of the diversity of Districts. Effective audit requires agreed criteria and standards but these were not identified. The Faculty criteria were not considered suitable. Directors of Public Health may develop criteria that they consider suitable for audit of their annual report in discussion, focusing upon their objectives in producing an annual report. This should be the first step in the audit process and an integral part of producing an annual report. PMID- 1515200 TI - Inappropriate reattendances in out-patient departments. AB - In an attempt to identify the number and characteristics of inappropriate reattendances at out-patient clinics, clinic doctors and patients in two specialties throughout a health district were given a questionnaire to complete on every patient attendance over one week. Four hundred and fifty-two patients were seen, and 293 were asked to reattend: in some 80 of the latter cases the clinic doctor felt that the GP could nevertheless manage the problem. These 'inappropriate' invitations to reattend were more likely to be given by junior hospital staff to long-standing patients of the clinic attending for monitoring purposes. The patients involved in these 'inappropriate' requests to reattend also tended to think that their GP could manage the problem. It is concluded that discharge policy needs to be made more explicit and training for juniors organized if out-patient resources are to be used most efficiently. PMID- 1515201 TI - A study of 'inappropriate' attendances to a paediatric Accident and Emergency Department. AB - 'Inappropriate' attendance to Accident and Emergency Departments (AEDs) has been shown in many studies to be a sizeable problem. However, only one previous study has investigated inappropriate attendance to these departments amongst children. In this paper we report an investigation of 'inappropriate' usage of a children's AED in Nottingham. Information was collected relating to a representative sample of children who attended this department during September and October 1989 by interviewing the adults accompanying them to the AED and by examining the children's AED medical records. Using defined criteria, the doctors treating each child within the AED assessed whether their attendance was 'appropriate' to the department. Nearly a third (30.1 per cent) of the patients studied were subsequently considered to be inappropriate attenders to this department. This proportion was highest amongst younger children, those from families of lower social class and those living closest to the hospital. 'Inappropriate' attendance was not found to relate to the availability of general practitioners. The reasons stated for choosing to attend the AED suggested that these attendances resulted from perceptions of the adult(s) accompanying the children to the department. In view of this finding, action is required to correct these perceptions, although it is recognized that this may be difficult to achieve. PMID- 1515202 TI - Improving obstetric outcomes in ethnic minorities: an evaluation of health advocacy in Hackney. AB - Ethnic differences in birthweight, perinatal mortality and other obstetric outcomes are now well known. In some districts with a significant ethnic minority population, services are provided for non-English-speaking women using maternity units. Various models have developed, including translators, interpreters, Linkworkers, the Department of Health funded Asian Mother and Baby Campaign and health advocates. This paper describes the evaluation of a health advocacy programme in Hackney, East London. The advocates do more than simply interpret language. Anecdotal examples of how this approach changes clinical practice encouraged the project steering group to commission a study to test the hypothesis that health advocacy could improve obstetric outcomes in non-English speaking women. A retrospective study was carried out comparing 1000 non-English speaking women delivering at the Mothers' Hospital, Hackney, in 1986 who had been accompanied by an advocate with women delivering at the same hospital in 1979 and at a reference hospital, Whipps Cross. The study found significant differences between the groups in three outcomes: antenatal length of stay, induction and mode of delivery. The changes in Caesarean section were of particular note. The rates rose from 11 to 17 per cent at the reference hospital, whereas they fell from 10.8 to 8.5 per cent at the Mothers' Hospital. This is highly statistically significant. Although these changes cannot be directly attributed to health advocacy, it was considered reasonable to deduce that improved communication could have influenced clinical practice. These findings suggest that health advocacy may offer a mechanism to address some of the adverse obstetric outcomes observed in ethnic minorities. PMID- 1515203 TI - Surgeons' views of day surgery: is there a consensus among providers? AB - Managers and purchasers of health services are being encouraged to expand day surgery as a means of providing high-quality care and reducing costs per case and waiting times. This study examined general surgeons' views of day surgery with particular reference to day case inguinal hernia repair. A postal questionnaire was completed by 240 consultants (85 per cent) in four Regional Health Authorities. Only 11 per cent were regularly undertaking day case inguinal hernia repair, a further 44 per cent held positive attitudes towards this form of treatment and 45 per cent were not interested, with attitudes varying by age and region. Major constraints perceived by those with positive attitudes were the lack of facilities at a hospital level and problems of community services. Negative attitudes were associated with concerns about post-operative complications and pain, and assumptions about patients' preferences. This demonstrates a considerable range in surgeons' attitudes to day surgery despite its formal endorsement by professional bodies, and identifies what are perceived as the organizational and clinical barriers to its wider introduction. It is suggested that eliciting provider views and concerns forms an important requirement for the successful implementation of organizational change. PMID- 1515204 TI - Assessing the effects of a health promotion programme for elderly people. AB - Physical exercise is an increasingly popular health promotion activity for elderly people, although evidence of its effectiveness is limited. We aimed to evaluate the impact of the exercise component of the Look After Yourself (LAY) package promoted by the Health Education Authority in two groups of elderly people attending the 10 weekly sessions which make up the LAY course. Classes 1 and 2 comprised 13 and 18 subjects, aged from 65 to 89 years, and from 58 to 87 years respectively. Class 1 subjects were white with the exception of one Jamaican man, and Class 2 subjects were all Afro-Caribbean. Subjects had measurements of shoulder joint flexibility, grip strength, blood pressure, weight and a self-perceived health questionnaire, the Nottingham Health Profile (NHP) completed at baseline, 10 weeks and at six months. Class 1 showed reductions in grip strength and a deterioration in pain and mobility dimensions of the NHP, whereas Class 2 showed large improvements in shoulder joint flexibility and a small and non-significant trend towards improved self-perceived health. Class 2 subjects felt that they had benefited, and just over half had continued with an exercise programme. These findings suggest that the effect of mild exercise on objective indicators and self-perceived health may depend on the context in which it is done, the type of exercise promoted, and that continued exercise is aided by the provision of further group classes. There is a need for evaluation of the impact of different types of exercise programmes, covering a wider range of indicators of fitness, in larger groups of elderly people. PMID- 1515205 TI - Quarterly communicable disease review. October to December 1991. From the PHLS Communicable Disease Surveillance Centre. PMID- 1515206 TI - Research for the review of RAWP. PMID- 1515207 TI - Health economists: good on theory but what about the facts? PMID- 1515208 TI - Current status of HIV-1 infection in the rabbit. PMID- 1515209 TI - In vivo derived HIV-1 nef gene products are heterogeneous and lack detectable nucleotide binding activity. AB - Multiple HIV-1 nef genes were cloned from lymphocyte DNA of asymptomatic seropositive individuals by polymerase chain reaction (PCR). Sequence analysis of these clones revealed a unique set of nef variants with premature terminations (PCRnef 1 and 6), mutations at sites of potential posttranslational modification (PCRnef 2 and 3) and deletions. In common with laboratory isolates of nef, strong sequence conservation was observed in the central domain of nef and in the myristylation target sequence, with variable domains toward the N- and C-termini of the molecule. The biochemical function of nef remains elusive however, as the products of these genes cloned into a bacterial expression system failed to reveal any nucleotide binding activity. PMID- 1515210 TI - Study of the interaction of HIV-1 and HIV-2 envelope glycoproteins with the CD4 receptor and role of N-glycans. AB - In order to further characterize the interaction of human immunodeficiency viruses (HIV) with the CD4 receptor at the molecular level, a binding test was performed using iodine-labeled glycoproteins, 125I-gp160 from HIV-1 and 125I gp140 from HIV-2, to bind to lymphoid cells expressing the CD4 receptor. The inhibition of binding of the radiolabeled glycoproteins to CD4+ cells by increasing concentrations of nonradiolabeled gp160 or gp140 was used to determine the affinity of the interaction between the glycoproteins and CD4. The gp-CD4 association occurs with a high affinity: K0.5 gpHIV-1 = 9 x 10(-9) M and K0.5 gpHIV-2 = 7 x 10(-8) M, indicating that the affinity of the interaction between HIV-2 gp140 and CD4 is 10 times lower than that observed with HIV-1 gp160. The N linked glycans of the HIV-1 and HIV-2 glycoproteins account for a high proportion of their molecular mass (about 50%). Total deglycosylation of gp160 and gp140 by enzymatic treatment with Endo F-N glycanase occurred under nondenaturing conditions, indicating the high accessibility of the N-linked glycan chains in the three-dimensional structure of the molecule. Moreover, the deglycosylated proteins retained a significant binding capacity to CD4. These results show that the carbohydrate chains of HIV-2 gp140, as those of HIV-1 gp160, do not play a major role in the gp-CD4 interaction. PMID- 1515211 TI - A randomized, double-blind, phase I/II trial of tumor necrosis factor and interferon-gamma for treatment of AIDS-related complex (Protocol 025 from the AIDS Clinical Trials Group). AB - To determine safety and efficacy of tumor necrosis factor (TNF) and interferon gamma (IFN gamma) in the treatment of patients with acquired immunodeficiency syndrome (AIDS)-related complex, a randomized, double-blind study was conducted. Twenty-five patients with AIDS-related complex and CD4 lymphocytes less than or equal to 500 x 10(6)/L attended an AIDS Clinical Trials Unit of a tertiary referral center. Patients were administered tumor necrosis factor (TNF) (10 micrograms/m2) or IFN gamma (10 micrograms/m2), or both intramuscularly three times weekly for 16 weeks. Side effects from all three preparations included fever, constitutional symptoms, and local reactions. No significant hematologic, hepatic, renal, or coagulation abnormalities were observed. CD4 lymphocyte counts, beta 2-microglobulin, p24 antigen levels, and anti-p24 antibody did not change significantly during therapy. Similarly, no significant change was noted in rates of HIV isolation from peripheral blood mononuclear cells or plasma. TNF and IFN gamma were tolerable after premedication with acetaminophen; however, no significant change in markers of human immunodeficiency virus infection was demonstrated. These cytokines alone do not appear to be of benefit, nor do they appear to hasten the progression of HIV infection. PMID- 1515212 TI - Three-drug synergistic inhibition of HIV-1 replication in vitro by 3'-fluoro-3' deoxythymidine, recombinant soluble CD4, and recombinant interferon-alpha. AB - 3'-Fluoro-3'deoxythymidine (FLT), recombinant soluble CD4 (CD4), and recombinant interferon-alpha (IFN alpha) were evaluated in two- and three-drug regimens against HIV-1 replication in vitro. Peripheral blood mononuclear cells were studied using p24 antigen production as the virologic endpoints. FLT showed 2.5 fold higher efficacy and a similar selectivity index to zidovudine. Drug interactions were evaluated by the median effect principle and the isobologram technique. FLT, CD4, and interferon alpha at noncytotoxic concentrations inhibited HIV-1 synergistically in two- and three-drug combinations with a combination index smaller than one and dose reduction index greater than one. The three-drug regimen provided greater virus suppression than the two-drug regimen. These results suggest that FLT is an alternative agent to AZT for the treatment of HIV infection either as a single agent or in combination with CD4 and/or interferon-alpha. PMID- 1515213 TI - Curdlan sulfate and HIV-1: II. In vitro long-term treatment of HIV-1 infection with curdlan sulfate. AB - Short-term (1 h) treatment with a newly synthesized sulfated polysaccharide, curdlan sulfate (CRDS), showed relatively weak blocking effects on the binding of human immunodeficiency virus type 1 (HIV-1) to the surface of H9 cells. To investigate whether long-term treatment with CRDS could strengthen this effect, CRDS in various doses (0.1, 1, 10, and 100 micrograms/ml) was used in 2-week treatment periods in four separate protocols or "Procedures." SF titers and p24 antigen levels were partially suppressed during long-term CRDS treatment but returned to control levels after the treatment was terminated. In addition, no direct cytotoxicity of CRDS to H9 cells or H9/HIV-1 cells was observed in vitro in the course of continuous exposure to 100 micrograms/ml CRDS for 2 weeks. These results demonstrate the effectiveness of long-term treatment of cells infected with HIV-1 in inhibiting virus expression. The most dramatic inhibition results were obtained when the compound was present both at the time of exposure of cells to virus and during a long-term follow-up treatment. These results show that CRDS inhibits both the cell-free and cell-associated transmission of HIV-1 to host cells and interferes with early events in virus infection. In contrast, CRDS exhibits no significant virucidal activity and has little effect on already infected cells. PMID- 1515214 TI - Treatment of the murine, retrovirus-induced lymphoproliferative immunodeficiency disease (LP-BM5) in C57BL/10 mice with the immunomodulator Imexon. AB - Imexon (4-imino-1, 3-diazabicyclo-(3.1.0)-hexan-2-one) a cyanoaziridine compound was studied in the treatment of the murine retrovirus-induced immunodeficiency disease model of AIDS (LP-BM5, MAIDS). Imexon, in dose-dependent fashion, partially prevented the development of hypergammaglobulinemia and splenomegaly, and partially prevented the decline in the phytohemagglutinin-induced proliferative response of spleen lymphocytes when started 1 or 15 days after virus inoculation. There was a statistically significant reduction in these disease-associated manifestations. When animals were treated starting 78 or 92 days after virus inoculation, lymphadenopathy was completely abrogated and survival was significantly prolonged in a dose-responsive manner. Since Imexon and other cyanoaziridine compounds have been safely administered to humans, we suggest that this class of compounds be further investigated in both large animal models of HIV infection and in patients with HIV-induced disease. PMID- 1515215 TI - The effects of AZT and DDI on pre- and postimplantation mammalian embryos: an in vivo and in vitro study. AB - This study reports the effects of the nucleoside analogs dideoxyinosine (DDI) and 3'-azido-3'-deoxythymidine (AZT) on mammalian embryonic development. When administered to pregnant mice (at concentrations ranging from 10 to 300 mg/kg/day), through all or part of gestation, AZT and DDI did not result in any visible effect on mouse embryos nor did they cause any obvious malformation or defect at birth or during postnatal growth. Similarly, when embryonic or fetal mouse or human cells (from brain, limb buds, or different organ rudiments) were exposed to AZT or DDI in vitro, cytotoxicity was observed only in the mM range, with AZT showing slightly higher cytotoxicity and brain cells appearing slightly more sensitive to both nucleosides. However, even in cultures treated with very high concentrations of AZT or DDI, the reduction in the number of terminally differentiated skeletal myotubes, cardiocytes, neurons, and chondrocytes was similar to the reduction in the total number of cells, indicating that AZT and DDI did not selectively inhibit differentiation of any of the above-mentioned cell types. Finally, preimplantation mouse embryos (at the 2-cell or 4-cell stage), treated in vitro with micromolar concentrations of AZT, were arrested at the 4-cell stage. DDI or other nucleoside analogs tested did not have this effect. PMID- 1515216 TI - Seroprevalence and cofactors of HTLV-I infection in Tumaco, Colombia. AB - This study presents an analysis of the factors associated with HTLV-I seroprevalence in the endemic area of Tumaco, Colombia. During June to August 1988, 1,077 individuals were selected at random from a population of 45,594. The overall prevalence rate of HTLV-I antibodies was 2.8%. Among females prevalence was significantly higher (p less than 0.02) than among males. Rates increased substantially with age. HTLV-I prevalence among individuals with history of use of intravenous medications was significantly higher (p less than 0.001) than in those without such history. Logistic regression analysis included age in years, indicators for male gender, and for i.v. injections, and their interactions. Age was very strongly associated to HTLV-I infection among females. At early ages prevalence was not different between sexes, but females presented a significantly higher rate than males after age 42. History of i.v. administered medications was very strongly associated in the univariate analysis and, although significance was borderline in the multivariate analysis, it had the effect of doubling the odds of HTLV-I infection. PMID- 1515217 TI - Frontiers in HIV-1 Therapy: fourth conference of the NIAID National Cooperative Drug Discovery Groups-HIV. AB - This summary describes current studies in antiviral targeting as reported at the Frontiers in HIV Therapy conference, November 3-7, 1991, in San Diego, California. In parallel with the progressive steps in HIV-1 replication, the meeting covered potential antiviral targets starting from the time HIV-1 docks with the CD4 receptor to virus release. The summary concludes with current research trends to block HIV-1 growth. PMID- 1515218 TI - Abstracts and lectures from the Annual Meeting Sponsored by the Laboratory of Tumor Cell Biology, National Cancer Institute. Bethesda, Maryland, September 1-8, 1991. PMID- 1515219 TI - The HIV/AIDS epidemic: a current picture. PMID- 1515220 TI - Pharmacologic regulation of HIV expression. PMID- 1515221 TI - Special lectures VIII. AIDS. PMID- 1515222 TI - "Extracellular Tax1 protein stimulates NF-kB and expression of NF-kB-responsive Ig kappa and TNF beta genes in lymphoid cells". PMID- 1515223 TI - New advances in the management of AIDS associated opportunistic infections. PMID- 1515224 TI - Transactivation of the murine c-myc gene by HTLV-1 tax is mediated by NFkB. PMID- 1515225 TI - Elevation of IL-6 in plasma cell tumorigenesis. PMID- 1515226 TI - Lymphoid germinal centers are reservoirs of HIV infection and account for the apparent latency of infection. PMID- 1515227 TI - The design and testing of HIV prophylactic vaccines. PMID- 1515228 TI - "Antigen processing and presentation". PMID- 1515229 TI - Functions of integrins in cell adhesion and migration. PMID- 1515230 TI - Metastases and drug-resistance as markers of cancer cell evolution. PMID- 1515231 TI - "The involvement of Fc receptors in tumor progression". PMID- 1515232 TI - Abnormal regional hypermethylation in cancer cells. AB - Let me summarize by reviewing a model which is meant to raise as many questions as it answers (Fig. 2). What I have discussed today are data suggesting that during progression of solid tumors, like colon cancer, an increased cellular DNA methylating capacity characterizes the initial stages of multi-clonal hyperplasia. Despite this increase, the altered pattern of DNA methylation which subsequently emerges is largely manifest by a widespread hypomethylation of DNA. However, on a more regional basis, areas of hypermethylation appear which can affect strategic areas such as normally unmethylated CpG islands. These shifted DNA methylation patterns have the capacity to both follow, or cause, chromatin changes that can both directly silence genes critical for normal cell maturation- and/or participate in the structural chromosome changes which constitute genetic instability during tumor progression (Fig. 2). I suggest that one must view these changes as an interchangeable cycle of events during tumor progression. The chromatin changes and abnormal methylation patterns can drive one another with increasingly deleterious effects as the malignant phenotype emerges (reviewed in Baylin, 1991). What are the molecular events that would initiate the above dynamics? A working construct model is shown in Fig. 3. As discussed for the normal adult cell, there is a delicate balance between the strategic location of DNA MTase, regulation of this enzyme, and rate of DNA synthesis at replication forks (top panel, Fig. 3). In pre-neoplastic and cancer cells, perhaps failure of cells to exit the cell cycle and halt DNA replication, facilitates some sort of pressure to increase cellular DNA methyltransferase activity (bottom panel, Fig. 3). This increase may involve loss of feedback inhibition of the enzyme during the post DNA replication phase. There are also probable structural alterations in the nucleus which may alter the geographic relationship between the DNA replication fork and DNA MTase. In consequence, many DNA areas that should be getting methylated do not, and novel areas of methylation also arise. This cycle of events leads to the imbalance of DNA methylation that I have talked about. Future investigations of these possibilities, and of their specific consequences for alterations of gene expression and chromosome structure, may reveal a key molecular step underlying virtually all stages of tumor progression. PMID- 1515233 TI - "Oncogenes as probes for cellular signal processes: the family of ETS genes". PMID- 1515234 TI - A gene alone may not make a tumor. PMID- 1515235 TI - "Ethics, politics, and medical obligations in biomedical research: the philosophical point of view". PMID- 1515236 TI - Treatment of advanced neuroblastoma. PMID- 1515238 TI - Assessing the quality of life of patients in cancer clinical trials: Common problems and common sense solutions. PMID- 1515237 TI - Learning from Cl-941 about pharmacokinetically guided dose escalation. PMID- 1515239 TI - The activity of single-agent carboplatin in advanced seminoma. AB - Between 1982 and 1990, 70 patients with advanced metastatic seminoma were treated with 4-6 courses of single-agent carboplatin (SAC) administered at 400 mg/m2 every 3-4 weeks. Treatment was of low toxicity and no patients suffered neurotoxicity, ototoxicity or significant renal damage. There was only one episode of neutropenic sepsis and no thrombocytopenic bleeding. The median follow up of surviving patients was 3 years. 16 patients have relapsed and 4 of these 16 have died, thus the actuarial 3-year relapse-free survival was 77% (95% CI 65 86%), cause-specific survival was 94% (95% CI 82-99%) and overall survival was 91% (95% CI 80-96%). The risk of relapse was reduced by post-chemotherapy irradiation (PCRT) to involved nodes, occurring in 1/20 patients treated with PCRT compared with 11/31 who could have been treated but were not (P = 0.04). Of the 16 patients who relapsed, 12(75%) have been salvaged with combination chemotherapy and remain free from further relapse with a median follow-up of 18 months. Though this level of survival is equivalent to that obtained with initial cisplatin-based combination chemotherapy, the recurrence rate indicates that SAC remains an investigative treatment, except for unfit patients. PMID- 1515240 TI - Pharmacokinetically guided dosing for intravenous melphalan: a pilot study in patients with advanced ovarian adenocarcinoma. AB - Pharmacokinetically guided administration of melphalan was investigated during a pilot study in patients with advanced ovarian adenocarcinoma. The schedule involved a fixed dose on day 1 (7.9 mg) followed by a second dose on day 2, calculated on the basis of pharmacokinetic data to achieve a target area under the concentration-time curve (AUC). 20 courses of intravenous melphalan were administered to 7 patients. AUC, standardised to 1 mg/m2, ranged between 4.3 and 8.9 (mg/l) min. In 12 fully evaluable courses, less than 15% deviation from the target AUC was found, showing that AUC monitoring was possible by means of the test dose. Pharmacodynamic effects showed a positive correlation with melphalan AUC. Myelosuppression appeared at 47 (mg/l) min and grade 3 or 4 haematological toxicities were observed in 4 cycles, associated with AUC values ranging between 86 and 112 (mg/l) min. Relative leucocyte decreases were well correlated with AUC values. PMID- 1515241 TI - Prognostic relevance of pS2 status in association with steroid receptor status and proliferative activity in node-negative breast cancer. AB - Expression of the oestrogen-regulated pS2 protein was investigated on paraffin embedded sections of primary breast tumours from 200 node-negative patients. Immunoreactivity was observed in 56% of the cases. pS2 expression was inversely correlated with tumour size and proliferative activity, whereas a direct correlation was observed with steroid receptor. 5-year relapse free survival was influenced by tumour size (P = 0.02), oestrogen receptor status (P less than 0.05), and proliferative activity (P less than 0.01). No difference in relapse free survival was observed between patients subdivided according to pS2 expression alone. However, among patients with oestrogen-receptor-negative tumors, pS2 expression predicted a shorter relapse-free survival. PMID- 1515242 TI - Toxicity of single-day high-dose vincristine, melphalan, etoposide and carboplatin consolidation with autologous bone marrow rescue in advanced neuroblastoma. AB - 16 unselected patients with advanced neuroblastoma were given high-dose consolidation chemotherapy with vincristine, melphalan, etoposide and carboplatin over 5 h followed by autologous bone marrow rescue. 3 patients died from treatment-related toxicity, 2 from disease, 1 is alive with disease and 10 are alive and disease-free a median of 12.5 months (range 2-38 months) after bone marrow rescue. All had bone marrow toxicity, most mucositis and 6 had seizures. Renal failure was unexpectedly severe. In the last 3 patients, administration of carboplatin was delayed by 18 h in an attempt to reduce renal damage. The results show that this regimen produces significant morbidity and has a high mortality. Although the overall outcome is encouraging, too few patients have been studied to gauge its efficacy. Whether such aggressive consolidation is necessary in heavily pretreated children with neuroblastoma remains unknown. PMID- 1515243 TI - Pilot study of high-dose vincristine, etoposide, carboplatin and melphalan with autologous bone marrow rescue in advanced neuroblastoma. AB - The efficacy and toxicity of a high-dose multiagent consolidation regimen, OMEC (vincristine, melphalan, etoposide and carboplatin), with autologous bone marrow rescue was studied in patients with poor-prognosis neuroblastoma, 20 patients were treated with OMEC, 18 after induction chemotherapy and 2 following relapse. All patients received, per m2, vincristine 4 mg, etoposide 1 g, carboplatin 1.0 1.75 g and melphalan 180 mg followed by bone marrow rescue. 4 patients (20%) died of treatment-related complications. Severe gastrointestinal toxicity occurred in all of these patients, and in 75% of patients overall. 1 of 5 patients with evaluable disease achieved complete remission. 13 patients (65%) have relapsed a median of 10 months (range 3-26) after receiving OMEC. Thus, OMEC was not more effective, yet more toxic, than high-dose melphalan given alone, and the use of similar multiagent regimens with overlapping toxicities in advanced neuroblastoma appears inadvisable. PMID- 1515244 TI - Can Karnofsky performance status be transformed to the Eastern Cooperative Oncology Group scoring scale and vice versa? AB - There is no consensus regarding the equivalence of performance status between the Karnofsky (KPS) and the Eastern Cooperative Oncology Group (ECOG) scales. In the present study KPS and ECOG scores were compared in 150 consecutive cancer patients. An empirical relation was established through regression analysis in a subsample of 75 patients and the results tested in the second subsample. Transformation tables including 95 and 66% confidence intervals were calculated. Both performance scales are highly correlated, but inferences about individual patients were subject to a high level of error. These results stress the difficulty of translating one score to another, especially in the range of lower performance status where a wide spread is observed. PMID- 1515245 TI - Psychological effects of participation in a prevention programme for individuals with increased risk for malignant melanoma. AB - The Swedish Melanoma Study Group runs a programme aimed at prevention and early detection of premalignant and malignant melanoma in families with two or more members having malignant melanoma. Psychological consequences of participation in this programme were studied. A questionnaire containing items concerning cognitive and emotional responses to the programme was completed by 115 consecutive individuals at their first visit to the clinic. The same questionnaire was administered by mail 7 months later. The levels of psychological and psychosomatic problems were relatively low at both points of assessment. No negative psychological effects were found, neither in the group with dysplastic naevus syndrome (DNS) with increased risk for malignant melanoma, nor in the group without dysplastic naevi. Only one variable, "emotional responses to the visit" differentiated between the groups, with higher scores in the group without DNS. A majority of the individuals expressed positive attitudes to the clinic. PMID- 1515246 TI - Mastectomy or conservation for early breast cancer: psychological morbidity. AB - A consecutive series of 197 women under 70 years of age with operable breast cancer, randomised to treatment by a conservation technique in comparison to mastectomy, were assessed using structured interviews. The prevalence of cases of anxiety and depression was high before treatment commenced, there were fewer cases in the conservation group but no significant difference at 3 or 12 months in the number of new cases, social adjustment, or capacity to return to work. Attitudes to treatment showed significant differences between the groups, more women in the conservation group were able to wear their usual clothes and most women rated the cosmetic result highly. Patients were more likely to stop sexual intercourse completely after mastectomy. An effective conservation technique should be an attractive treatment choice available to selected women with early breast cancer. PMID- 1515247 TI - Comparison of three protracted antiemetic regimens for the control of delayed emesis in cisplatin-treated patients. AB - Antiemetic activity of three protracted regimens for the control of cisplatin evoked delayed emesis was explored. 63 patients were randomly assigned to receive one of three protracted antiemetic schedules over 4 days. Group C patients received dexamethasone 8 mg twice daily on days 2 and 3, then 4 mg twice daily on days 4 and 5; in group B, alizapride 2.5 mg/kg four times daily on days 2-5 plus dexamethasone as in group C was administered; and in group A, metoclopramide 0.5 mg/kg four times daily on days 2-5 plus dexamethasone was given at the same dose schedule as in groups C and B. Complete protection from delayed vomiting was achieved in 44% of group C, 30% of B and 70% of group A (P = 0.02). Mild side effects were noted in all three groups. A higher complete protection for delayed emesis was obtained in metoclopramide-dexamethasone-treated patients. Neither of the regimens used in the protection of delayed emesis controlled late nausea. PMID- 1515248 TI - Drug-sensitivity testing in patients with human oesophageal squamous cell carcinoma. AB - To evaluate the response to chemotherapeutic agents against human oesophageal cancer, 19 samples were tested by the human tumour clonogenic assay (HTCA), 21 samples by subrenal capsule assay (SRCA) and 33 samples by SRCA with immunosuppressant (IS-SRCA). The evaluability rate of was 21% for HTCA, 95% for SRCA and 91% for IS-SRCA. No active agent was detected by HTCA, however, 29% of the drugs tested by SRCA and 22% by IS-SRCA were considered to be active. Histological analysis revealed substantial inflammatory infiltrates and poor tumour cell preservation with SRCA; however, infiltrates were minimal and there was a high degree of tumour cell preservation with IS-SRCA. The response rates of IS-SRCA were comparable with those of prior clinical tests for each drug. These results suggested that IS-SRCA is the most useful drug sensitivity test for human oesophageal cancer. PMID- 1515249 TI - CA72-4 compared with carcinoembryonic antigen as a tumour marker for gastric cancer. AB - Serum levels of a newly identified, tumour-associated antigen, CA72-4, were measured in 86 patients with histologically proven gastric carcinoma. Preoperative levels of CA72-4 in serum tended to be higher with increased dissemination of the cancer. Elevated levels of CA72-4 (above 5.0 U/ml) were significantly more frequent than those of carcinoembryonic antigen (CEA) (above 5.6 ng/ml) in patients with stage III or IV (P less than 0.01) carcinoma, in patients with Borrmann type 4 (P less than 0.01), and in patients with peritoneal metastasis (P less than 0.01). No correlation was seen between serum levels of CA72-4 and those of CEA. Serum levels of CA72-4 were lower 1 month after gastrectomy in 25 of 39 patients with resected cancers. In each of 4 patients with recurrence, lower levels of CA72-4 after gastrectomy were replaced by elevated levels on detection of the recurrence of cancer. These results indicate that CA72-4 is highly specific to gastric cancer and may be more reliable as a tumour marker than CEA for gastric cancer. PMID- 1515250 TI - Feasibility of measuring oxygen tension in uterine cervix carcinoma. AB - Cellular hypoxia is a cause of radioresistance. The oxygen tension (pO2) in normal tissues and in tumours can be measured by polarography. In this feasibility study we have measured the tissue pO2 of 10 patients suffering from uterine cervix carcinoma, using the Eppendorf histograph. The measurements were performed at the time of the brachytherapy after external radiotherapy. The machine was found to be reliable and no adverse effect was noted. The mean pO2 values in tumours were lower than those of normal tissues. PMID- 1515251 TI - The long-term retention of platinum in human tissues following the administration of cisplatin or carboplatin for cancer chemotherapy. AB - Mass spectrometry has been used to study the distribution and retention of platinum in the tissues of patients following the administration of cisplatin or carboplatin. Blood platinum was measured up to 2 years and renal excretion up to 5 years after treatment. Platinum concentrations in plasma and red cells fell according to a power function, approximately as the inverse square of the time after administration. The concentration in the urine fell more slowly. Necropsy samples were used to examine the distribution of platinum in various human organs up to 17 months after treatment. The highest concentrations were found in the liver, which retained approximately 2% of the dose. Although the results were scattered between patients, there was little loss of platinum after about 1 month. The prolonged retention of platinum may be relevant to long-term toxicity. PMID- 1515252 TI - Phase I study of intravenous 4-hydroxyanisole. AB - 4-Hydroxyanisole is a depigmenting agent which has been shown to have activity against malignant melanoma when given intra-arterially in man. An intravenous dose escalation study has been carried out with the aim of obtaining maximum plasma concentrations in a 5 day schedule. 8 patients entered this study which was stopped because of drug toxicity after 3 patients had been treated at the third dose escalation of 15 g/m2. 2 patients had WHO grade 4 liver and one also grade 4 renal toxicity and another had grade 4 haemoglobin toxicity. Extrapolated plateau plasma levels between 112 and 860 mumol/l were obtained, which in vitro studies suggested would be cytotoxic. Hopefully, newer analogues will have a greater specificity for the melanin pathway with less toxicity. PMID- 1515253 TI - Reducing the toxicity of the combined modality therapy of favourable stage Hodgkin's disease. PMID- 1515254 TI - Curative non-surgical combined treatment of squamous cell carcinoma of the oesophagus. AB - Between April 1982 and June 1989, 65 patients (15 T1, 13 T2, 32 T3, 5 T4) with squamous cell carcinoma of the oesophagus were treated with a curative intent with multimodality combined treatment. A first course of 5-fluorouracil and cisplatin was given during work up, especially if NdYAG laser therapy was used. Irradiation was started 3-4 weeks after induction and two courses of concomitant chemotherapy were given during the radio therapy (aiming at 64 Gy over 7 weeks). Actuarial survival was 79.6% at 1, 36.7% at 3 and 26.7% at 5 years. 5 year survival rates were 56.3% for T1, 29.8% for T2 and 12.9% for T3. All T4 cases died within 16 months. Complete initial disease response was achieved in 76%. Tolerance was good. Thus patients with squamous cell carcinoma of the oesophagus can have long survival and may be cured with combined modality therapy. This treatment may be an alternative to radical surgery when there is a high risk of operative mortality. PMID- 1515255 TI - Prospective randomised study of double hemi-body irradiation with and without subsequent maintenance recombinant alpha 2b interferon on survival in patients with relapsed multiple myeloma. AB - Immediately before first hemi-body irradiation, 59 patients with relapsed multiple myeloma were randomised to receive or not to receive subsequent alpha-2b interferon maintenance. 13 patients (22%) [8 of 31 (26%) controls, 5 of 28 (18%) in the interferon arm] received single hemi-body irradiation alone due to progressive disease and/or persistent cytopoenias following the initial procedure. Mean time between upper and lower hemi-body irradiation was 69 days (range 35-294). Of 23 patients randomised to receive interferon and completing double hemi-body irradiation, 15 (65%) achieved peripheral blood counts adequate to allow interferon administration as per study criteria commencing at a mean 116 days (61-241) from time of study entry. The mean period of interferon therapy, starting at a mean 65 days (26-160) post second hemi-body irradiation, is 16.4 months (2-33.5). There was no significant difference in median survival durations (10 months) from time of initial radiotherapy between control and interferon patients. PMID- 1515256 TI - High-dose chemotherapy and autologous bone marrow transplantation for relapsed and refractory Hodgkin's disease. AB - The results of high-dose chemotherapy with melphalan or melphalan (carmustine) etoposide for 66 consecutive patients with relapsed or resistant Hodgkin's disease are described. 55 patients were evaluable for response and 22% of these achieved complete remission and 59% partial remission. The actuarial survival at 2 years was 45% and the principal factors determining survival were the sensitivity of the disease to therapy given before high-dose chemotherapy and the type of treatment received. Intensive chemotherapy with autologous bone marrow transplantation can produce long-term survivors among patients for whom long-term survival would otherwise be improbable. However, this treatment remains toxic with an uncertain place in management. PMID- 1515257 TI - Adrenal masses in lung cancer: sonographic diagnosis and follow-up. AB - Ultrasound has become an important diagnostic modality in the staging of patients with lung cancer. Between 1980 and 1990, 410 patients with histologically proved lung cancer were evaluated. In 44 patients (11%) an adrenal mass was discovered on ultrasound; in 13 patients it was isolated, and in 31 further evidence of abdominal disease was shown. Sonographic follow-up examinations of adrenal masses showed changes of size in all but 2 patients, and were therefore found to be adrenal metastases. In the 2 patients with isolated and stable adrenal disease, fine-needle biopsy revealed adenomas. Adrenal masses in patients with lung cancer are more likely to be metastatic than benign. The existence of neoplastic adrenal disease can be retrospectively confirmed by changes of size during sonographic follow-up examinations in almost all patients. Histologically verification would only appear necessary in stable adrenal disease and in cases with isolated adrenal disease in which prompt diagnosis affects treatment decision. PMID- 1515258 TI - Droloxifene, a new anti-oestrogen in postmenopausal advanced breast cancer: preliminary results of a double-blind dose-finding phase II trial. AB - Droloxifene (3-OH-tamoxifen citrate) is a novel anti-oestrogen with a higher affinity for oestrogen receptors (ER), a lower oestrogenic to anti-oestrogenic activity ratio and faster pharmacokinetics compared with tamoxifen. From May 1988 to April 1991, 369 postmenopausal women with metastatic or locally unresectable breast cancer of which the ER or progesterone receptor status was positive or unknown, were randomised to receive an oral dose of 20, 40 or 100 mg droloxifene once daily. 43 Brazilian, Canadian and European centres took part in this double blind phase II trial. 60 women were ineligible for violation of entry criteria; 20 were inevaluable and 15 still await definitive response evaluation. 234 patients have been evaluated for response. The over-all objective response rate (complete plus partial) was 92/234 (39.3%): 23/74 (31.1%) for 20 mg, 33/74 (44.6%) for 40 mg and 36/86 (41.9%) for 100 mg (not significantly different within this dose range). There was no significant difference in time to tumour progression between the three doses. Toxicity was minimal at all doses. These preliminary results show that droloxifene is active against advanced breast cancer. Because of its outstanding preclinical characteristics, the drug warrants large-scale clinical investigation. PMID- 1515259 TI - Recent efforts to establish an in vivo model as a new experimental tool in the study of Hodgkin's disease. PMID- 1515260 TI - ChlVPP: reducing toxicity in the treatment of Hodgkin's disease. PMID- 1515261 TI - Expression of cathepsin D in head and neck cancer. AB - To determine overexpression of cathepsin D in head and neck tumours we examined cytosols from 53 primary tumours, nine cytosols of lymph node metastases and 12 cytosols from adjacent normal tissue. We found a significantly lower concentration in normal tissue compared with tumour cytosol as well as with metastases, even when we compared tumours and corresponding metastases pairwise. In addition, we found a significantly higher concentration of cathepsin D in five lymph node metastases than in the corresponding tumours. We conclude that the reported role of cathepsin D is not restricted to breast cancer but could also be important in head and neck cancer. PMID- 1515262 TI - Axillary dissection of level I and II lymph nodes is important in breast cancer classification. The Danish Breast Cancer Cooperative Group (DBCG). AB - In order to define the term "a node-negative patient", the axillary nodal status at the primary operation for breast cancer was evaluated in 13,851 patients registered by the Danish Breast Cancer Cooperative Group (DBCG). The determinants for node negativity in primary breast cancer were the number of lymph nodes removed and the tumour size. The number of lymph nodes removed should be at least 10 to exclude misclassification of node-positive patients as node negative. There was a strong relationship between tumour size and the percentage of node-negative patients. Another observation was that high rate of node negativity was associated with low histological grade. The age of the patients had no influence on node negativity. Where 10 or more negative lymph nodes were removed, significantly better axillary recurrence-free survival (P less than 0.0001), over all recurrence-free survival (P less than 0.0001) and survival (P less than 0.005) were found. PMID- 1515263 TI - A rapid anticancer drug screening assay by [14C] thymidine uptake in cultured human cancer cells. AB - A rapid screening test by suppression of DNA synthesis in cancer cells was developed with [methyl-14C]-thymidine (14C-TdR), a microculture filtration plate and a radiochromatoscanner. Mitomycin, tamoxifen and 5-fluorouracil (5-FU) were tested against four human gastric cancer cell lines and HeLa cells. The tetrazolium-based colorimetric (MTT) assay underestimated cell inactivation by mitomycin in three cell lines compared with the cell count and the 14C-TdR assays. Inactivation by 5-FU in one cell line by 14C-TdR uptake was considerably lower than that by other methods. Thus neither the radio-labelled DNA precursor uptake nor the MTT assay is suitable for every anticancer drug but they are complementary. PMID- 1515264 TI - Relationship of cell cycle parameters to in vitro and in vivo chemosensitivity for a series of Lewis lung carcinoma lines. AB - The sensitivity of three Lewis lung carcinoma sublines, which grow in culture and in vivo, and vary in in vivo drug sensitivity, have been compared using topoisomerase II poisons amsacrine, amsacrine analogue CI-921, doxorubicin and etoposide. D10 (drug concentration for 10% clonogenic survival) values were determined in vitro for low and high density cultures, and ex vivo for cells from subcutaneous tumours. The cytokinetic parameters of these populations were obtained by flow cytometric analysis of bromodeoxyuridine-labelled cells. Regression analysis showed that logarithmic D10 values were significantly correlated (r greater than 0.95) with G1- and S-phase proportions and highly correlated (r = 0.99) with calculated G1 transit times. The slopes of the regression lines were similar for all topoisomerase II poisons tested and it is suggested that this slope reflects the disappearance of topoisomerase II during G1 phase. PMID- 1515266 TI - Comparison of intra-arterial versus intravenous 5-fluorouracil administration on epidermal squamous cell carcinoma in sheep. AB - Clinical evidence that intra-arterial chemotherapy is more effective in regressing head and neck cancers than equivalent intravenous doses is lacking. Intra-arterial versus intravenous 5-fluorouracil infusion was compared in a naturally occurring, auricular epidermal squamous cell cancer in sheep. Of 18 lesions infused intra-arterially and of 18 infused intravenously with the same dose, 39 and 11%, respectively responded objectively (over 50% regression); mean (S.E.) tumour volume reduction was 37(23) and 18(22)%, respectively. There was a statistically significant difference in the mean tumour response and in numbers of tumours regressing by at least 40% of tumour volume (50% of intra-arterial treated tumours compared with 11% of intravenous treated lesions) after the 16 day total infusion time in favour of intra-arterial treatment. Technically, the intra-arterial route in this model was an improvement on previous small animal models. These findings lend support to the need for continuing clinical study of intra-arterial infusion. PMID- 1515265 TI - Epidermal growth factor receptor and transforming growth factor alpha expression in human ovarian carcinomas. AB - The varying tumorbiological behaviour of ovarian carcinomas probably influences operability, response to chemotherapy, being one of the most relevant prognostic factors. Because it is believed that an activation of the epidermal growth factor/transforming growth factor alpha (EGF/TGF alpha) signal pathway could be involved, we analysed the expression of epidermal growth factor receptor (EGFR) and TGF alpha with molecular-chemical, biochemical and immunohistochemical methods in 42 ovarian carcinomas, 4 ovarian metastasis, 2 other malignant ovarian tumours, and in 25 nonmalignant tissues (ovary, myometrium). No major rearrangements or amplification of the EGFR or TGF alpha genes were found. In non malignant tissues no strong EGFR or TGF alpha signals were detected. TGF alpha is mainly produced by the tumour cells as shown by immunohistochemistry. Four different high molecular weight forms (20-48 kD) were detected in malignant tissues by western blot analysis. PMID- 1515267 TI - Expression of glutathione-S-transferase-pi in human tumours. AB - Expression of glutathione-S-transferase-pi (GST-pi) gene was quantitatively analysed on various human tumours (renal cell, colorectal, head and neck, ovarian carcinomas, soft tissue sarcomas; non-Hodgkin lymphomas) and on the corresponding normal tissues when available (kidney, colorectum and head and neck). GST-pi mRNA expression level was found to be significantly higher in tumours (P less than 0.01) than in the normal counterparts (mainly 7.3, 3.5- and 3.0-fold in colorectal, head and neck, and renal carcinomas, respectively). Most tumours displayed a significant relationship between higher GST-pi expression level and poor differentiation grade of tumour cells, thus suggesting a relationship between GST-pi activity, neoplastic transformation and cellular differentiation grade. The high requirement of GST-pi activity neoplastic cells displayed was not singularly related to cellular replication rate. Finally, GST-pi gene expression levels were not affected by chemotherapeutic treatments. PMID- 1515269 TI - Lack of therapeutic gain when low dose rate interstitial radiotherapy is combined with cisplatin in an animal tumour model. AB - The interaction of cisplatin with low dose rate interstitial radiotherapy was studied in an animal tumour model with a range of dose rats commonly used in clinical low dose rate brachytherapy. Small pieces of R1-rhabdomyosarcoma were implanted subcutaneously in the flanks of female Wag/Rij rats. When the tumour had grown to the desired treatment volume, four afterloading catheters were inserted in the tumour in a square geometry, and a fixed spacing was attained by means of a template. Subsequently, four 2 cm Ir192 wires were inserted. A range of tumour doses of 20-120 Gy at a mean dose rate of 48 cGy/h was applied; 15 mins before the implant an intraperitoneal bolus injection of 3 mg/kg cisplatin was given. For growth delay and cure rate, no modification of the effects of low dose rate brachytherapy by the addition of cisplatin was observed. The observed effects of the combination of cisplatin with low dose rate interstitial radiation in relation to the animal tumour are discussed. PMID- 1515268 TI - Methotrexate alters the fatty acid composition of NC adenocarcinoma cells in culture. AB - The effects of methotrexate and indomethacin alone and in combination have been examined on the fatty acid (FA) composition of total cellular lipids in cultured NC adenocarcinoma cells. These studies show that methotrexate can alter the lipid content of cancer cells. Methotrexate 16 ng/ml incubated with NC cells for 2 days increased the content of various FAs. When used alone, indomethacin 1 microgram/ml or methotrexate 8 ng/ml had no significant effect, but in combination caused FA increases, usually to about the same extent as with the higher concentration of methotrexate alone. No FA changes were seen up to 3 h with these drug concentrations or with methotrexate up to 10 micrograms/ml alone or with INDO 1 microgram/ml. These effects may explain previous findings that indomethacin potentiates methotrexate, an interaction which may be important in cancer therapy. PMID- 1515270 TI - The influence of age on treatment choice and survival of elderly breast cancer patients in south-eastern Netherlands: a population-based study. AB - The influence of age on treatment choice and survival was studied in 2268 breast cancer patients of 55 years and older reported to the Eindhoven Cancer Registry from 1975 to 1987. Among patients of 75 years and older, stage I and II tumours occurred less often, whereas stage IIIb and undefined tumours occurred more often than among younger patients. Physicians were found to be less likely to treat women of 75 years and older with adjuvant radiotherapy after a mastectomy. Instead, these women received either surgery alone or surgery followed by hormonal therapy. Surgical procedures in the oldest age group were also less extensive. The 10-year relative survival for women over 74 years (32%) was significantly worse than that for younger patients (57%). Multivariate analyses showed that this poor outcome for the oldest age group was largely related to their unfavourable stage distribution: stage-specific survival appeared to be similar in all age groups. Age-related differences in treatment did not have an effect on survival. PMID- 1515271 TI - Coffee consumption and bladder cancer risk. AB - The relation between consumption of regular and decaffeinated coffee and other methylxanthine-containing beverages and bladder cancer was analysed in a case control study in two different areas of northern Italy (555 cases and 855 controls). The multivariate relative risk (RR) adjusted for smoking, occupation and sociodemographic variables for coffee drinkers versus non-drinkers was 1.3 (95% CI 1.0-1.8). The RR was 1.2 for one cup of coffee per day, 1.4 for two, 1.5 for three and 1.4 for four or more (P = 0.05). RRs for current drinkers were 1.5 (0.9-2.4) for decaffeinated coffee, 0.9 (0.6-1.2) for tea, and 0.6 (0.3-1.4) for cola. With reference to duration of consumption of coffee, RRs were 1.2 for less than 30 years or 1.4 for 30 years or more. Coffee-related RRs were higher in the older age group and in ex-smokers. Among 105 cases and 338 controls who had never smoked, RRs were 1.9 for one or two cups per day, 1.8 for three and 1.5 for four or more (trend not significant). A higher prevalence of coffee drinking among bladder cancer cases than controls was confirmed, with no clear dose-risk relation. PMID- 1515272 TI - The effect of family history of cancer, religion, parity and migrant status on survival in colorectal cancer. The Melbourne Colorectal Cancer Study. AB - The association between 5-year survival and several risk factors was investigated in 705 histologically confirmed, new cases of colorectal adenocarcinoma as one aspect of a comprehensive population-based study of large bowel cancer incidence, aetiology and survival--the Melbourne Colorectal Cancer Study. 5-year survival was not influenced by the previously determined risk of a family history of colorectal cancer in near-relatives. Similarly, other previously determined risk factors of religion, number of children, age at birth of first child and migrant status did not influence survival. PMID- 1515273 TI - Linkage of death certification of AIDS and cancer registration in Vaud, Switzerland. AB - 58 death certifications (40 males and 18 females) of residents of the Canton of Vaud (Switzerland) which reported AIDS as the cause of death in 1986-1989 were matched with the list of incident cancers available since 1974 from the Vaud Cancer Registry. Such linkage was successful for 20 individuals (age range 25-63, median 37), mostly males (18/20), homosexual or bisexual (11/18) and affected by Kaposi's sarcoma (14 males and 1 female). Other identified neoplasms included one Burkitt's lymphoma, one prostate adenocarcinoma and one multiple myeloma (whose histological picture included, however, lymphocytosis in addition to plasmocytosis). Three additional malignancies (one undifferentiated skin cancer, one carcinoma of the salivary glands and one in situ cervical carcinoma), and one myelodysplastic syndrome had also been diagnosed from 1 to 2 years before AIDS death. Cancer was mentioned on the death certificate, in addition to AIDS, in only 2 cases. Albeit of limited size, the present report confirms that a systematic integration of AIDS and cancer registration statistics provides additional information, of particular interest for histological classification, on the AIDS-cancer relationship. PMID- 1515274 TI - Trends in cancer survival in Vaud, Switzerland. AB - Survival rates from the Vaud Cancer Registry were compared for incident cases registered in 1974-1978 and 1979-1983. No appreciable difference was evident for most major cancer sites: 5-year relative survival rates were 0.21 in 1974-1978 and 0.23 in 1979-1983 for stomach, 0.49 and 0.46 for colon, 0.45 and 0.47 for rectum, 0.04 and 0.03 for pancreas, 0.08 and 0.10 for lung, 0.41 and 0.42 for kidney, 0.21 and 0.13 for brain, and 0.32 and 0.30 for multiple myeloma, respectively. A modest advancement in 5-year relative survival rates was, however, registered for total cancer mortality (non-melanomatous tumours excluded, from 0.41 to 0.43) while, with regard to specific sites, a significant improvement was seen only for cancer of the testis (from 0.73 to 0.88). More than 10% non-significant improvements in survival were recorded for melanomatous skin cancer (from 0.67 to 0.78), thyroid cancer (from 0.73 to 0.85), particularly in females, non-Hodgkin lymphomas (from 0.37 to 0.45), Hodgkin's disease (from 0.61 to 0.78), cancer of the ovary (from 0.28 to 0.32) and the prostate (from 0.44 to 0.52). However, significant declines in survival rates were seen for cancer of the larynx, gallbladder and biliary tract, and for connective tissue neoplasms. A few differences in the modification of relative survival rates according to age (less than 60 versus greater than or equal to 60 years) were noted for a few cancer sites. Changes were larger in older patients with respect to cancer of the prostate and thyroid and non-Hodgkin lymphomas (increases) and connective neoplasms (decreases). Conversely, changes in survival were greater or restricted to younger individuals for testis, bladder and leukaemias (improvements) and cancer of the mouth or pharynx (decline), thus suggesting the different play of age-specific biological characteristics of some tumours, in addition to diagnostic improvements and gradual spread of effective cancer treatments to more advanced age groups. PMID- 1515275 TI - Are tumours immortal? PMID- 1515276 TI - Clinical and biological characteristics of malignant lymphomas in HIV-infected patients. PMID- 1515277 TI - Trends of cancer mortality in Europe, 1955-1989: V, Lymphohaemopoietic and all cancers. PMID- 1515278 TI - Recombinant human GM-CSF enhances the anti-proliferative activity of vitamin D in MCF-7 human breast cancer clonogenic cells. PMID- 1515279 TI - Late onset of gallbladder carcinoma with meningeal carcinomatosis. PMID- 1515280 TI - A phase II study of epirubicin in patients with advanced adenocarcinoma of the pancreas. PMID- 1515281 TI - Acute febrile neutrophilic dermatosis (Sweet's syndrome) in metastatic breast cancer. PMID- 1515282 TI - PLS-based quantitative structure-activity relationship for substituted benzamides of clebopride type. Application of experimental design in drug design. AB - The advantageous approach of using an experimentally designed training set as the basis for establishing a quantitative structure-activity relationship with good predictive capability is described. The training set was selected from a fractional factorial design scheme based on a principal component description of physico-chemical parameters of aromatic substituents. The derived model successfully predicts the activities of additional substituted benzamides of 6 methoxy-N-(4-piperidyl)salicylamide type. The major influence on activity of the 3-substituent is demonstrated. PMID- 1515283 TI - Tobacco chemistry. 73. 4,6,8-trihydroxy-11-capnosene-2,10-dione, a new cembrane derived bicyclic diterpenoid from tobacco. AB - A new diterpenoid containing a rare carbobicyclic cembrane-derived skeleton, the capnosane skeleton, has been isolated from flowers of Greek tobacco. It has been identified as (1S*,3R*,4S*,6R*,7R*,8R*,11Z)-4,6,8-trihydroxy-11-capnosene- 2,10 dione by spectral methods and X-ray analysis of the corresponding benzoate. A full account of the X-ray work is given. PMID- 1515284 TI - Understanding the nature of congenital division of the atrial chambers. PMID- 1515285 TI - Assessment of right ventricular function and its role in clinical practice. PMID- 1515286 TI - Left ventricular filling characteristics in pulmonary hypertension: a new mode of ventricular interaction. AB - OBJECTIVE: To examine the effects of pulmonary hypertension on left ventricular diastolic function and to relate the findings to possible mechanisms of interdependence between the right and left sides of the heart in ventricular disease. DESIGN: A retrospective and prospective analysis of echocardiographic and Doppler studies. SETTING: A tertiary referral centre for both cardiac and pulmonary disease. PATIENTS: 29 patients with pulmonary hypertension (12 primary pulmonary hypertension, 10 pulmonary fibrosis, five atrial septal defect (ASD), and two scleroderma) were compared with a control group of 10 patients with an enlarged right ventricle but normal pulmonary artery pressure (six ASD, one after ASD closure, one ASD and pulmonary valvotomy, one tricuspid valve endocarditis and repair, and one pulmonary fibrosis). None had clinical or echocardiographic evidence of intrinsic left ventricular disease. MAIN OUTCOME MEASURES: M mode echocardiographic measurements were made of septal thickness, and left and right ventricular internal cavity dimensions. Doppler derived right ventricular to right atrial pressure drop, and time intervals were measured, as were isovolumic relaxation time, and Doppler left ventricular filling characteristics. RESULTS: The peak right ventricular to right atrial pressure gradient was (mean (SD)) 60 (16) mm Hg in pulmonary hypertensive patients, and 18 (5) mm Hg in controls. The time intervals P2 to the end of the tricuspid regurgitation, and P2 to the start of tricuspid flow were both prolonged in patients with pulmonary hypertension compared with controls (115 (60) and 120 (40) v 40 (15) and 45 (10) ms, p values less than 0.001). Pulmonary hypertensive patients commonly had a dominant A wave on the transmitral Doppler (23/29); however, all the controls had a dominant E wave. Isovolumic relaxation time of the left ventricle was prolonged in pulmonary hypertensive patients compared with controls, measured as both A2 to mitral valve opening (80 (25) v 50 (15) ms) and as A2 to the start of mitral flow (105 (30) v 60 (15) ms, p values less than 0.001). The delay from mitral valve opening to the start of transmitral flow was longer in patients with pulmonary hypertension (30 (15) ms) compared with controls (10 (10) ms, p less than 0.001). At the time of mitral opening there was a right ventricular to right atrial gradient of 12 (10) mm Hg in pulmonary hypertensive patients, but this was negligible in controls (0.4 (0.3) mm Hg, p less than 0.001). CONCLUSIONS: Prolonged decline of right ventricular tension, the direct result of severe pulmonary hypertension, may appear as prolonged tricuspid regurgitation. It persists until after mitral valve opening on the left side of the heart, where events during isovolumic relaxation are disorganised, and subsequent filling is impaired. These effects are likely to be mediated through the interventricular septum, and this right-left ventricular asynchrony may represent a hitherto unrecognised mode of ventricular interaction. PMID- 1515287 TI - Vasodilator myocardial perfusion imaging: demonstration of local electrophysiological changes of ischaemia. AB - OBJECTIVE: To examine the incidence and severity of myocardial ischaemia provoked in the course of perfusion scintigraphy by coronary vasodilators using endocardial recordings of steady state monophasic action potentials as an independent marker of early localised myocardial ischaemia. PATIENTS: 31 men undergoing routine cardiac catheterisation for investigation of chest pain were studied. SETTING: A tertiary cardiac referral centre. DESIGN: Single site monophasic action potentials were recorded from the left or right ventricle or both (50 recording sites) during intravenous infusion of dipyridamole (0.015 mg/kg/min) for four minutes. Heart rate was held constant with atrial pacing at 20% above the patient's resting rate. Technetium-99m hexakis-2-methoxy-2 methylpropyl-isonitrile (MIBI) was administered four minutes after dipyridamole, and single photon emission tomographic imaging was performed an hour later. Rest images were obtained the next day (two day, two dose protocol). Recordings were divided into three groups based on the scintigraphic perfusion characteristics and coronary anatomical data for the action potential recording site: group 1- recordings from areas with a normal perfusion pattern (n = 30), group 2- recordings from areas with a perfusion defect and subtended by significantly narrowed coronary arteries without obvious angiographic collateral supply (n = 10), and group 3--recordings from areas with a perfusion defect and subtended by occluded arteries with angiographically evident collaterals from adjacent vessels (n = 10). RESULTS: There were changes in the duration of the monophasic action potential indicative of ischaemia--that is, shortening of duration of steady state action potential--in 18 of the 20 recordings from areas of abnormal perfusion. Peak changes were apparent eight minutes from the start of the dipyridamole infusion. Mean (SEM) values for duration of the action potential between control and peak effect at eight minutes were 276.5 (5.3) ms v 276.6 (5.4) for group 1 (NS), 289.6 (4.7) ms v 278.4 (4.9) ms for group 2 (p less than 0.001), and 269.6 (5.7) ms v 242.0 (4.4) for group 3 (p less than 0.0001). These changes were significantly different between the three groups (p less than 0.01). ST segment changes on the surface electrocardiogram were seen in only eight patients, all with areas of viable myocardium supplied by collateral vessels. CONCLUSIONS: These data provide strong evidence for the presence of myocardial ischaemia in regions of reversible perfusion defects induced by dipyridamole. This study also shows that such ischaemia is more intense and more likely to be seen when myocardial viability is dependent on collateral circulation. PMID- 1515288 TI - Characteristics of presystolic flow in the superior vena cava: new thoughts on a forgotten sound. AB - Cross sectional, M mode, and Doppler echocardiography, apexcardiography, and phonocardiography were used to characterise presystolic cardiovascular sounds in three patients with ventricular disease. Although the aetiology was different (dilated cardiomyopathy, primary pulmonary hypertension, and chronic pulmonary thromboembolic disease), in each case the presystolic sound was associated with a rapid change in acceleration of blood and with flow reversal in the superior vena cava, and could only be recorded at the right sternal edge or over the jugular veins. Such flow characteristics may be explained by a raised ventricular end diastolic pressure with reduced compliance. Use of these techniques helps to understand the cause of a previously described but little recognised heart sound, and adds weight to the interpretation of its presence in disease. PMID- 1515289 TI - Remnant of the common pulmonary vein mistaken for a left atrial mass: clarification by transoesophageal echocardiography. AB - Faulty incorporation of the common pulmonary vein leaves it as a distinct structure posteriorly, into which the pulmonary veins empty. This "chamber" is separated from the anterior "fetal" left atrium (containing the left atrial appendage and communicating with the mitral valve) by a diaphragm, and is known as cor triatriatum, one of the rarest of cardiac malformations. Less pronounced but still incomplete regression of this vein would result in the persistence of a portion of the common pulmonary vein appearing as a mass along the lateral wall of the left atrium at the junction of the left atrial appendage and left upper pulmonary vein. In two patients, both referred for evaluation of a left atrial mass, transoesophageal echocardiography identified the "mass" as a remnant of the common pulmonary vein. Cardiologists need to be aware of this structural remnant and its possible variants so as to avoid misdiagnosis of this prominence as an atrial tumour or mass. PMID- 1515290 TI - Coronary venous lipid peroxide concentrations after coronary angioplasty: correlation with biochemical and electrocardiographic evidence of myocardial ischaemia. AB - BACKGROUND: Raised lipid peroxide concentrations in coronary venous plasma have been reported after coronary angioplasty in humans. This may reflect increased free radical activity after myocardial ischaemia and reperfusion. If so, it may be possible to correlate lipid peroxide concentrations with the degree of myocardial ischaemia produced during angioplasty. METHODS: 15 patients (age range 42-70; 12 men) with stable angina pectoris undergoing angioplasty of a proximal left anterior descending coronary artery stenosis were studied. Plasma lipid peroxide and lactate concentrations were measured in sequential blood samples taken from the great cardiac vein before and immediately after one to five serial 60 second balloon inflations. The maximum ST segment shift during each balloon inflation was also measured. RESULTS: Lipid peroxide concentrations in coronary venous plasma were raised from pre-angioplasty values by more than 2 SDs of the relevant measurement error after 27 out of 46 (59%) balloon inflations. Lactate concentrations were raised after 43 out of 46 (93%) balloon inflations. No significant difference was found between the peak percentage change of either lipid peroxide or lactate concentrations after any of the first three serial inflations. The maximum ST segment shift after each of the first three serial inflations was also similar. Coronary venous lactate concentrations after balloon inflation correlated positively with the maximum ST segment shift, but did not correlate with lipid peroxide concentrations. CONCLUSIONS: Raised lipid peroxide concentrations in coronary venous plasma can be detected in humans after balloon angioplasty. There is no positive correlation between lipid peroxide concentrations in coronary venous plasma after angioplasty and the degree of preceding myocardial ischaemia as assessed by either ST segment shift or lactate production. These indices showed that one to three serial 60 second balloon inflations each produce a similar degree of myocardial ischaemia. The origin of the raised lipid peroxide concentrations in coronary venous plasma after angioplasty remains unknown. PMID- 1515291 TI - Thallium scans in syndrome X. AB - OBJECTIVE: To review thallium scans in patients with angina and normal coronary arteriograms. DESIGN: Retrospective review of data. SETTING: Regional cardiac centre in Glasgow. PATIENTS: 100 patients selected from those undergoing diagnostic angiography for typical angina who had normal arteriograms (around 10%), no other cardiovascular abnormality, and available thallium scans (performed routinely before angiography). MAIN OUTCOME MEASURES: Coronary arteriography, exercise tests, and gated thallium scans at peak exercise. RESULTS: The exercise test was positive in 30 and negative in 70 patients. Thallium defects were found in 98 patients, but no consistent pattern and no significant correlation existed between the extent of thallium defect and positive exercise test or exercise tolerance. CONCLUSIONS: Thallium defects described in 98 of 100 patients with angina and normal coronary arteriograms suggest that microvascular angina may be commoner than is generally appreciated. PMID- 1515292 TI - Use of an autoperfusion catheter in the treatment of acute refractory vessel closure after coronary balloon angioplasty: immediate and six month follow up results. AB - OBJECTIVE: To determine the usefulness of the Stack autopersion dilatation catheter in patients with acute recurrent vessel closure during coronary angioplasty. DESIGN: Prospective data collection. SETTING: University hospital. PATIENTS: In 37 of 1003 consecutive patients undergoing angioplasty between November 1989 and December 1990 acute vessel closure developed that could not be redilated by a conventional balloon catheter. 13 (35%) of these 37 patients were sent immediately for emergency bypass surgery. INTERVENTION: In the remaining 24 patients an attempt was made to reopen the vessel with a Stack catheter. MAIN OUTCOME MEASURE: Successful reopening of the vessel. All successfully treated patients were followed for at least six months to detect recurrent ischaemia. RESULTS: In 16 patients (67%) the Stack procedure was successful. Of the eight patients in whom reopening of the occluded vessel was not achieved, seven were sent for bypass surgery and one was successfully treated by emergency stent implantation. The 16 patients successfully treated with the Stack autoperfusion system were followed up for a mean (SD) of 6.7 (2.6) (range 2 to 11) months. Ten patients remained symptom free but early clinical restenosis developed in four (25%). Overall, only three (19%) of 16 patients experienced recurrence of severe (class III-IV) symptoms and required further mechanical revascularisation. CONCLUSION: These data support the use of the Stack autoperfusion catheter system in selected patients with acute vessel closure not responsive to attempted redilatation with conventional balloon catheters. The short-term outcome seen in this series of patients who were successfully treated with this coronary autoperfusion system is encouraging. PMID- 1515293 TI - Giant right atrial diverticulum: an unusual cause of Wolff-Parkinson-White syndrome. AB - A case of a giant right atrial diverticulum associated with neonatal supraventricular tachycardia is reported. The electrocardiogram in sinus rhythm showed pre-excitation that may have been caused by the right atrial diverticulum adhering to the right ventricle. PMID- 1515295 TI - Proceedings from the British Cardiac Society, annual general meeting. May 26-29, 1992. Abstracts. PMID- 1515294 TI - A characteristic continuous wave Doppler signal in cor triatriatum? AB - Continuous wave Doppler recordings of the turbulent jet through the restrictive orifice of a left atrial partition in a patient with corrected transposition of the great arteries and cor triatriatum showed alternate bands of high intensity diastolic and low intensity systolic signals with preservation of the normal configuration of the diastolic E and A peaks. It is thought that Doppler studies in cor triatriatum will provide useful complementary haemodynamic information in the echocardiographic diagnosis of this anomaly. PMID- 1515296 TI - Proceedings of the British Cardiac Society, general annual meeting. May 26-29, 1992. Abstracts. PMID- 1515297 TI - Cor triatriatum sinister, not mitral stenosis, in an adult with previous Sydenham's chorea: diagnosis and preoperative assessment by cross sectional echocardiography. AB - In cor triatriatum sinister, one of the rarest congenital cardiac anomalies, a membrane divides the left atrium into a pulmonary venous component above and the vestibule below. The importance of the anomaly lies in the effects of the resultant pulmonary venous obstruction that usually present in the first year of life and can mimic obstructed total anomalous venous drainage or congenital mitral stenosis. A case presented as mitral stenosis in the third decade of life, ten years after a well documented episode of Sydenham's chorea. The diagnosis was made rapidly by transthoracic echocardiography and transoesophageal echocardiography was used for complete assessment. Cardiac catheterisation added nothing to the non-invasive diagnosis or the preoperative assessment. Uncomplicated corrective surgery was undertaken. PMID- 1515298 TI - 'In God we trust--all others must document'. PMID- 1515299 TI - Health care reform: who's got the answer? PMID- 1515300 TI - HIV-associated papulosquamous diseases. AB - Persons infected with the human immunodeficiency virus (HIV) can develop a variety of dermatoses in which the primary lesions are scaly papules or plaques. These dermatoses can be the presenting clinical manifestations of HIV infection. Depending on the degree of immune dysfunction, the clinical and histopathologic appearance may be typical or quite unusual. PMID- 1515301 TI - Primary bacterial skin infections. AB - Bacterial infections are among the most frequent inflammatory skin disorders. This continuing education article describes certain aspects of bacterial infections and outlines the medical and the nursing management. A comprehensive nursing care plan is listed. PMID- 1515302 TI - Sexuality and self-concept: issues in skin disease. AB - Self-concept is closely tied to feelings of sexuality. Therefore, comprehensive nursing care of patients with skin disorders should include sexuality issues. This article addresses methods of assessment and a variety of interventions in dealing with sexuality and skin disease. PMID- 1515303 TI - What's your assessment? Neurotic excoriations. PMID- 1515304 TI - Results of the cross-Canada survey of recombinant human erythropoietin (r-HuEPO) therapy programs. The Medicine Group (Canada) Ltd. PMID- 1515305 TI - Preparing for certification: Halifax nephrology nurses--in quest of excellence. PMID- 1515306 TI - Teaching tool for renal transplant recipients using Orem's self-care model. PMID- 1515307 TI - Politics: the health of the nation. PMID- 1515308 TI - Complementary therapies. A healing touch. PMID- 1515309 TI - Regional trends: a portrait of Britain. PMID- 1515310 TI - Reducing pain and anxiety in children. AB - Children faced with clinical procedures may become distressed in anticipation of the experience of pain. This article describes psychological interventions designed to minimise the trauma children associate with potentially distressing situations. Although time-consuming, the author suggests they are valid tools in the control of pain. PMID- 1515311 TI - Genetic counselling. Alzheimer's disease: advances in genetics. AB - Recent advances in DNA technology have allowed identification of those carrying the gene mutation for early onset Alzheimer's disease in some families, and provide the prospect of an effective treatment or cure in the future. While last week's article questioned the existence of late onset Alzheimer's as a distinct disease entity, this one illustrates how and why these scientific advances may have far-reaching psychosocial consequences for some family members. It suggests why there is likely to be an increase in demand for the kind of information and support which can be offered by a genetic counselling service. PMID- 1515312 TI - Issues in nursing and health. Patient access to health records. AB - The Access to Health Records Act was passed in 1990. To provide time for training to be given and procedures to be put in place, it did not come into effect until November 1 1991. The Act was promulgated as a result of pressure from people who wanted access to their notes and health professionals who recognised the benefits of open relationships with the people for whom they cared. PMID- 1515313 TI - Quality assurance: using BS 5750 in health care settings. AB - This article places the issue of standards within the arena of a quality service. It argues that standards of quality can only be turned into reality if they are developed through the discipline of a quality assurance system, combined with the motivation of a quality culture. A quality assurance system, British Standard (BS) 5750, is briefly outlined and attention is given to examining the mechanisms for defining the specific requirements necessary to develop quality assurance within residential care homes. This is based on the authors' experience of working with Napier House, the first caring enterprise in Europe working directly with patients or residents to obtain the BS 5750. PMID- 1515314 TI - The care service of the not-too-distant future: the hospihotel. PMID- 1515315 TI - Alternative medicine: alternative roads to hell? PMID- 1515316 TI - Health promotion: passing the screen test. PMID- 1515317 TI - Working parents: new parents' fazed returns. PMID- 1515318 TI - Cardiology update. Digital imaging. PMID- 1515319 TI - Cardiology update. Computerised tomography. PMID- 1515320 TI - Cardiology update. Magnetic resonance. PMID- 1515321 TI - Cardiology update. Hope and charity. PMID- 1515322 TI - Cardiology update. The sound revolution. PMID- 1515323 TI - Cardiology update. Thallium scanning. PMID- 1515325 TI - Politics: revisiting old haunts. Interview by Bill Doult. PMID- 1515324 TI - HIV/AIDS. PMID- 1515326 TI - Complementary therapies: coming full circle. Interview by Charlotte Alderman. PMID- 1515327 TI - Health of the nation: aiming too high? PMID- 1515328 TI - NHS reforms: a vision of the future. Interview by John Naish. PMID- 1515329 TI - Sexual activity after myocardial infarction. AB - The resumption of sexual activity after myocardial infarction can be an area of concern for patients, and one that may be difficult for nurses to address. Patients often fear that resuming sex will be dangerous to their perceived fragile health status, while nursing staff can be reluctant to broach a subject which may cause embarrassment to both parties. The author discusses the aims of the patient education process, and includes practical advice that can be given. He stresses the need to consider the circumstances of the individual patient, thereby avoiding vague and generalised advice that may be of little value. PMID- 1515330 TI - The nursing process: Fijian experiences. AB - The nursing process is almost taken for granted in the United Kingdom. Fijian nurses, when faced with its implementation, found it was poorly understood and uncommonly used. This study highlights some of the perceptions of Fijian nurses to the nursing process and how it is intended to overcome the challenges these pose. PMID- 1515331 TI - Issues in nursing and health. Paediatric nursing: a philosophy of care. PMID- 1515332 TI - Evaluating growth hormone treatment. AB - The consequences in later life for people whose growth in childhood has been restricted can be profound, often with severe emotional or psychological effects. The author defines the causes of short stature and describes clinical trials being undertaken to evaluate the use of growth hormone in children who do not appear to have growth hormone deficiency. PMID- 1515333 TI - Is elderly care research-based? AB - Nurses working with elderly people, and students considering the specialty as a career option, may develop negative attitudes about the value of the work they do. These often derive from the perception that their efforts do not improve patients' problems, and a misconception that what they do is intuitive rather than based in research. Such tensions can lead to the development of 'burnout' and the rapid demoralisation of the workforce. Roger Watson shows how nursing elderly people, particularly those with dementia who live in continuing care settings, calls on high degrees of technical and interpersonal skills, and demonstrates how the roots of the specialty are deeply entrenched in research. PMID- 1515335 TI - Education: at the back of the NVQ. PMID- 1515334 TI - Wrongly failed student nurses. PMID- 1515336 TI - Communication: nursing's towering babble. PMID- 1515338 TI - Tradimus. Student placements: a qualified failure. PMID- 1515337 TI - Tradimus. Blinkered judgements. PMID- 1515339 TI - Tradimus. Jargon: understanding sweet nothing. PMID- 1515340 TI - Tradimus. Tutor support: spare a thought for the mentors. PMID- 1515341 TI - Tradimus. Sexuality: not in front of the students. PMID- 1515342 TI - Tradimus. Student support: holistic student care. PMID- 1515343 TI - Tradimus. Student placements: a casualty of ward. PMID- 1515344 TI - Incidence of bladder cancer in a cohort of workers exposed to 4-chloro-o toluidine while synthesising chlordimeform. AB - Between 1982 and 1990 seven cases of bladder cancer were detected in a group of 49 workers who were synthesising chlordimeform from 4-chloro-o-toluidine. Latency periods ranged from 15 to 23 years. The incidence of bladder tumours in this group was significantly higher than that of the cancer registers of the former GDR, Saarland, and Denmark by factors of 89.7, 53.8, and 35.0 respectively. This provides further evidence that monocyclic aromatic amines such as 4-chloro-o toluidine may be carcinogenic in humans. PMID- 1515345 TI - Morbidity study of extruder personnel with potential exposure to brominated dioxins and furans. I. Results of blood monitoring and immunological tests. AB - The potential for exposure of employees to polybrominated dibenzofurans (PBDFs) and dibenzo-p-dioxins (PBDDs) during extrusion blending of resins containing decabromodiphenyl ether was established through previous air monitoring (area samples) and biomonitoring studies. The findings presented herein are further biomonitoring results for 42 employees and immunological tests for exposed and referent employees. Among potentially exposed men, 2,3,7,8-TBDF and 2,3,7,8-TBDD concentrations in blood lipid ranged from non-detectable to 112 parts per trillion (ppt) and from non-detectable to 478 ppt respectively. Biomonitoring results correlated well with assignments in the extruder work area when adjusted for process changes and engineering improvements and provided biological half life estimates of between 1.1 and 1.9 years for 2,3,7,8-TBDF and between 2.9 and 10.8 years for 2,3,7,8-TBDD. Results for 16 measures of the immune system were examined in relation to exposure (exposed v referent group) and in relation to the biomonitoring data. Some individual trends in immunological parameters with exposure and covariates such as age and cigarette smoking were found (for example, an increase in complement C4 with increasing concentrations of PBDFs and PBDDs, increased lymphocyte subpopulation counts with cigarette smoking); however, the overall clinical assessment was that the immune system of exposed employees was not adversely impacted at these burdens of PBDFs and PBDDs. PMID- 1515347 TI - Longitudinal studies of exposure to cadmium. AB - Measurements of urinary proteins, blood and urinary cadmium, and in vivo kidney and liver cadmium have been made for a group of workers at several times between 1981 and 1990. The possibility of the introduction of measurement artifacts due to the use of different in vivo measurement systems has been assessed and is considered to be small. Changes in cadmium body burden with time have been studied in relation to kidney function. The results suggest several interesting patterns, although more data are needed to elucidate these further. They do, however, show the effectiveness of good hygiene in the workplace. PMID- 1515346 TI - Effects of occupational exposure to mercury vapour on the central nervous system. AB - Possible effects of mercury on the central nervous system (CNS) were examined in a group of chloralkali workers exposed to mercury (n = 89) and compared with a control group (n = 75), by registration of subjective symptoms, personality changes, forearm tremor, and performance on six computerised psychometric tests in the two groups. The groups were similar in age, education, verbal comprehension, and work tasks. In the chloralkali group, median blood mercury concentration (B-Hg) was 55 nmol/l, serum mercury concentration (S-Hg) 45 nmol/l, and urine mercury concentration (U-Hg) 14.3 nmol/mmol creatinine (25.4 micrograms/g creatinine). Corresponding concentrations in the control group were 15 nmol/l, 4 nmol/l, and 1.1 nmol/mmol creatinine (1.9 micrograms/g creatinine) respectively. The number of self reported symptoms, the scores for tiredness and confusion in the profile of mood states (POMS), and the degree of neuroticism in the Eysenck personality inventory (EPI), were significantly higher in the mercury exposed group compared with the controls. Performance on the psychometric tests and tremor frequency spectra did not differ significantly between the two groups. Dose-response calculations showed weak but statistically significant relations between symptom prevalence and current mercury concentrations in both blood and urine. The performance on three of the psychometric tests was negatively correlated with earlier peak exposures. The findings indicate a slight mercury induced effect on the CNS among the chloralkali workers. PMID- 1515348 TI - Peripheral markers of neurochemical function among workers exposed to styrene. AB - A cross sectional study of biological markers of neurochemical function in peripheral blood cells, and self reported nervous system symptoms, was conducted among 60 workers exposed to styrene in three reinforced plastics plants and 18 reference workers not exposed to styrene or other solvents. Concentrations of styrene in the air at the plants ranged from less than 1 to 160 ppm. Biomarkers of neurochemical function measured were: sigma receptor binding in lymphocytes, monoamine oxidase type B (MAO-B) activity in platelets, and serotonin uptake by platelets. Blood styrene concentration was used as the exposure index to take account of the use of protective equipment and dermal uptake. Four blood styrene exposure groups were defined as: non-exposed (reference) and exposed to less than 0.05, 0.05-0.19, and greater than or equal to 0.20 micrograms/ml. The prevalences of headache, dizziness, light headedness, fatigue, irritability, memory loss, and feeling "drunk" at work increased with increasing blood styrene concentration. No effect on sigma receptor binding was seen. A slight positive correlation was found for uptake of serotonin, which has been used as an exposure related effect indicator in previous studies of workers exposed to solvents. The MAO-B activity decreased with increasing blood styrene concentration; the mean (SE) MAO-B values for the four groups were 34.2 (3.0), 28.1 (5.3), 20.1 (4.8), and 16.9 (7.7) pmol/10(7) cells/min. The MAO-B activity also correlated negatively with the number of reported nervous system symptoms, whereas no associations were seen between prevalence of symptoms and either serotonin uptake or sigma receptor binding. The findings for MAO-B activity are consistent with previously reported experimental data, and suggest that MAO-B may be a useful marker of styrene neurotoxicity. PMID- 1515349 TI - Decline in spirometric variables in grain workers from start of employment: differential effect of duration of follow up. AB - Prospective study of 164 young men from the start of employment in grain elevators showed that of those seen at the initial evaluation of respiratory state only 30% were available for a complete four year follow up. The drop out of subjects could represent a health related selection leading to the underestimation of respiratory effects of exposure to grain dust as assessed in the survivor group. This hypothesis was examined by comparisons of longitudinal changes in lung function in four groups defined by the duration of follow up involving the initial examination and periodic evaluations after one, two, and four years of work. Sixty four men were tested only on the initial examination (group I), 18 underwent two (group II), 31 underwent three (group III), and 51 (group IV) all four examinations. The groups had similar mean ages (range: 19.4 20.1 years), mean duration of previous exposure to grain dust (range: 8-13 weeks), smoking habits, lung function, and prevalences of respiratory symptoms evaluated on the initial occasion. The average decline in lung function over the first year was associated with duration of follow up. The annual decline in FVC (ml) was 58 in group II, 41 in group III and -55 (increase) in group IV; the decline in FEV1 (ml) was 224, 130, and 70 respectively. The differences for the annual declines of FEV1, FEF25-759 Vmax509 and Vmax25 were significant between groups II and IV, and the FEF25-759 Vmax509 and Vmax25 differed significantly between groups II and III. The results show that the restriction of analysis to the survivors may underestimate the relation between work and respiratory impairment. PMID- 1515350 TI - Immune response to flour and dust mites in a United Kingdom bakery. AB - In a study of 279 United Kingdom bakery workers a high prevalence of immunological response to storage mites was found. To determine whether this was the consequence of exposure to storage mites in bakery work, a population of salt packing workers was examined as a comparison group not at occupational risk of exposure to storage mites. Forty two per cent of both groups were atopic (had a positive skin prick response greater than negative controls to D pteronyssinus, grass pollen, or cat fur by 2 mm or more) and 33% had an immediate skin prick test response to at least one of four storage mites (L destructor, G domesticus, T putrescentiae, A Siro). A higher percentage of the salt packing workers than the bakery workers had a positive radioallergosorbent test (RAST) (greater than or equal to 0.35 PRU) to D pteronyssinus and to the four storage mites. Logistic regression analysis identified atopy as the most significant variable for a positive skin test and RAST response to storage mites in both groups of workers. RAST inhibition was used to analyse extracted area and personal air samples. Analysis of static area samples for aeroallergen showed immunological identity with flour but L destructor was found in only one of seven exposed filters. The concentration of airborne flour was related to exposure rank of perceived dustiness and gravimetric measurement of total dust. Nineteen out of 32 filters from workers in jobs with higher dust exposure (rank >/=6) had a level of > 10 microgram/m(3) flour whereas this concentrations was exceeded in only one of 23 filters from workers in low dust exposure (< rank 6). It is concluded that storage mites are not of special significance in allergic responses in bakery workers. The development of immunological (and airway) responsiveness to inhaled flour dust is increased in those exposed to higher concentrations of airborne allergen, which appears to be predominantly flour and not storage mites. PMID- 1515351 TI - Radiographic osteoarthrosis in the acromioclavicular joint resulting from manual work or exposure to vibration. AB - The hypothesis that manual work and exposure to vibration are antecedents to the development of osteoarthrosis was assessed employing a cross sectional study design. The frequency of osteoarthrosis in the acromioclavicular joint was studied in three groups of workers in the construction industry. Two groups were manual workers (54 bricklayers and 55 rock blasters); the third group consisted of 98 foremen. The radiographic appearance of the right and left acromioclavicular joints was classified into one of five grades of osteoarthrosis. A protocol was developed to assess exposure on the basis of job title, years of manual work, total weight lifted during working life, and total hours of exposure to vibrating tools. Odds ratios for job titles (manual worker v foreman) and for years of manual work as indicators of exposure were of similar magnitude of around 2.5. Construction workers who had lifted more than 709 tonnes had an increased risk of developing severe osteoarthrosis of the right acromioclavicular joint, odds ratio: 2.62 (95% confidence interval (95% CI), 1.13 6.06). The odds ratio for the left side was 7.67 (95% CI, 2.76-21.34). In the analysis of vibration exposure, workers who had been highly exposed to vibration had an odds ratio of 1.99 (95% CI, 1.00-3.92) on the right side and 2.20 (95% CI, 1.07-4.56) on the left. This effect almost disappeared after simultaneous adjustment for manual work. Occupational and ergonomic factors, such as the sum of lifted tonnes during working life, job title, and the sum of years of manual work seem to be risk factors for osteoarthrosis of the acromioclavicular joint, whereas vibration alone was a weaker risk factor. PMID- 1515352 TI - Shearer's wrist: the carpal tunnel syndrome as an occupational disease in professional sheep shearers. PMID- 1515353 TI - Asthma and contact urticaria from latex gloves in a hospital nurse. PMID- 1515354 TI - Malignant pleural mesothelioma caused by non-occupational childhood exposure to asbestos. PMID- 1515355 TI - Cigarette smoking and small irregular opacities. PMID- 1515356 TI - The course of respiration and circulation in death due to typical hanging. AB - Experiments were carried out on 15 dogs to investigate the course of respiration and circulation during the agonal period of death due to typical hanging. Animals were asphyxiated by a method simulating typical hanging. Electrocardiogram (ECG), electroencephalogram (EEG), blood pressure (BP) in the femoral artery and intrathoracic pressure (ITP) were registered. In typical hanging, the course of respiration was characterized by shorter stages of dyspnoea and initial apnoea and a longer stage of the terminal respiration when compared with obstructive asphyxia. However, the whole time of the course of respiration and circulation in typical hanging was almost the same as that in obstructive asphyxia. The BP increased rapidly, was maintained during the dyspnoea stage, and then decreased gradually. EEG disappeared with, or a short time after, the end of the dyspnoea stage. The increased heart rate in the dyspnoea stage remained until circulatory collapse. The analysis of the ECG complexes revealed that the heart muscle adapted to oxygen deficiency during typical hanging. PMID- 1515357 TI - Polymorphism of coagulation factor XIII B subunit: further occurrence of FXIIIB*15 in Japanese and phenotyping in bloodstains. AB - The polymorphism of FXIIIB was investigated in 555 unrelated Japanese individuals using isoelectric focusing and immunoblotting. Five common phenotypes and a rare variant type FXIIIB 15-3 were observed. The allele frequencies were FXIIIB*1 = 0.3063, FXIIIB*2 = 0.0162, FXIIIB*3 = 0.6766 and FXIIIB*15 = 0.0009. Phenotyping was also possible from bloodstains stored at 37 degrees C for up to 4 months and from bloodstains stored at room temperature and at 4 degrees C for over 6 months. The FXIIIB system can provide a new powerful genetic marker for the medicolegal grouping of bloodstains. PMID- 1515358 TI - Glycyrrhizin and glycyrrhetinic acid determination from formalin-fixed tissue. AB - Glycyrrhetinic acid (GA), the main metabolic product of glycyrrhizin (GLY), could be detected in formalin-fixed tissue from a man who died 6 hours after therapeutic administration of a GLY-containing agent. GA was extracted from homogenized formalin-fixed liver tissue and 3 ng GA/g could be detected by HPLC. The extraction from formalin-fixed liver tissue gave the same retention time peak as the GLY control. GA could also be detected by mass spectrometry in the blood sample. This confirms that the man had received a GLY-containing agent for therapeutic use prior to his death and that GA can be determined from formalin fixed tissue. PMID- 1515359 TI - Genetic polymorphism of orosomucoid (ORM1 and ORM2) in Lombardy (Italy). AB - Orosomucoid subtypes have been analysed in 600 unrelated individuals from the Brescia Area (Lombardy-Italy) by the isoelectric focusing technique and immunoprinting. Five ORM1 phenotypes were observed. The ORM2 pattern was found to be virtually monomorphic, but one variant with an additional single band was found. The estimated allele frequencies were: ORM1*F1 = 0.5992, ORM1*F2 = 0.0150, ORM1*S = 0.3858. PMID- 1515360 TI - Non-traumatic rupture of the superior mesenteric vein with hemoretroperitoneum. AB - A case of rupture of the superior mesenteric vein with hemoretroperitoneum is described. The autopsy revealed the presence of an acute pancreatitis and thrombosis of the superior mesenteric artery. From the histological findings it appeared that the acute pancreatitis had damaged the venous wall from the outside and that the portal system overload, caused by the superior mesenteric artery thrombosis and the anomalous termination of the inferior mesenteric vein, acted from the inside of the vein causing its rupture. To our knowledge this is the first report of a rupture of the superior mesenteric vein caused by acute pancreatitis and resulting in hemoretroperitoneum. PMID- 1515361 TI - The "Scandinavian Star" ferry disaster 1990--a challenge to forensic odontology. AB - With 158 victims, the fire on board the "Scandinavian Star" was one of the world's worst ferry disasters. A team of identification experts, including dentists, were employed to secure evidence for identification and to remove the victims from the ferry. Four parallel teams, each with 2 dentists, examined and autopsied the victims at the Institute of Forensic Medicine, University of Oslo. Using the INTERPOL Disaster Victim Identification forms and aided by computers, all victims were identified within 17 days. Dental identity could be established in 107 cases (68%). PMID- 1515362 TI - Postmortem toxico-kinetics of co-proxamol. AB - Postmortem drug redistribution in suicidal poisonings by co-proxamol (dextropropoxyphene and paracetamol) has been studied. Analytical data for 8 tissue samples, including muscle and fat, up to 8 blood samples, and gastric and small bowel contents were obtained in 4 cases. Blood samples were taken from multiple sites at the start of autopsy and after 24 or 48 h. Concentrations of both drugs were site dependent with the lowest concentrations in peripheral blood. Paracetamol concentrations varied two to threefold and propoxyphene concentrations varied seven to tenfold. Pulmonary artery concentrations of paracetamol did not change significantly with time; propoxyphene concentrations typically increased twofold over 24 h and threefold over 48 h. Propoxyphene concentrations in the inferior vena cava increased unpredictably but occasionally significantly (up to sevenfold). For both drugs the most dramatic elevations of blood concentrations were seen in the aorta; in one case paracetamol rose to 1.9 g/l, 8 times the peripheral blood concentration and 4 times the liver level (454 mg/kg); propoxyphene rose to 191.5 mg/l, 55 times the peripheral blood concentration. This appears to reflect postmortem diffusion of unabsorbed drug from the gastric lumen. It is likely that markedly higher concentrations in the putrefactive fluid from the left pleural cavity as compared with the right also reflect diffusion from the stomach. PMID- 1515363 TI - Tyre tread marks on the body without internal injuries. AB - Two cases are presented involving a 5-year-old boy with tyre tread impressions on the back and right arm and a 4-year-old girl with tread marks on the head but both had no internal injuries. These cases suggest that injuries to internal organs do not always occur when the trunk or head is run over by the wheels of a vehicle. PMID- 1515364 TI - Improved section bonding using silanated glass slides--application protocol. AB - Silanated slides provide excellent tissue adhesion for routine histology, immunohistochemistry and in situ hybridization of frozen, paraffin embedded material or cell smears. An easy and inexpensive method of treating glass microscope slides with triethoxysilylpropylamine is reported. PMID- 1515365 TI - DNA extraction from mixtures of body fluid using mild preferential lysis. AB - A modification to the DNA extraction method "preferential lysis" (Gill et al. 1985) is proposed which can be applied to DNA mixtures of vaginal cells and spermatozoa. In mixtures with a low sperm content the further loss of sperm DNA caused by the extraction can be avoided by using "mild preferential lysis". Amplification by PCR (polymerase chain reaction) then yields sufficient DNA to be able to identify both components in the mixture. PMID- 1515366 TI - Group-specific component (GC) polymorphism in Cadiz (southern Spain). AB - The genetic polymorphism of group-specific component (GC) was analysed in a sample of 443 healthy unrelated subjects of both sexes resident in the province of Cadiz (Southern Spain). Isoelectric focusing was carried out in polyacrylamide gels followed by staining with coomassie blue R 250. The estimated gene frequencies were as follows: GC*1S = 0.6185; GC*1F = 0.1162; GC*2 = 0.2652. PMID- 1515367 TI - Gene-specific DNA interstrand cross-links produced by nitrogen mustard in the human tumor cell line Colo320HSR. AB - Genomic and gene-specific DNA interstrand cross-links produced by nitrogen mustard (HN2) were measured in the human tumor cell line Colo320HSR. Following exposures that produced greater than or equal to 1 log cell kill, it was found that HN2-induced DNA interstrand cross-links were produced and processed in a heterogeneous fashion within the genome. Cross-links were detected in the amplified, overexpressed c-myc oncogene, whereas in the weakly expressed N-ras gene and the nontranscribed, high copy number alpha-satellite sequence (of chromosome 20), cross-links were not detected. The cross-links in the c-myc oncogene disappeared more rapidly than total genomic cross-links. These results suggest that HN2-induced DNA interstrand cross-links are produced and processed in the genome in a nonrandom fashion. PMID- 1515368 TI - Transcriptional control of epidermal growth factor receptor by retinoic acid. AB - Retinoic acid (RA) and epidermal growth factor (EGF) regulate growth and differentiation of epithelial cells. RA has both direct and indirect effects on gene expression. Direct effects result from modulation of the transcriptional activity of genes, which contain RA response elements (RARE) recognized by trans acting nuclear RA receptors (RARs). A second indirect mechanism for the modulatory effects of RA is by the induction or repression of growth factors and growth factor receptors. There is evidence for functional interactions between RA and the EGF receptor (EGFR). RA enhances the proliferative response of cultured keratinocytes to EGF, increases the number of EGFRs on the surface of some cells, and induces EGFR promoter activity in most cells. In contrast, immunoprecipitation, Northern blot, and nuclear run-on analysis described in this paper show that RA suppresses EGFR synthesis at the transcriptional level in human epidermoid carcinoma ME180 cells. Deletion analysis of EGFR gene promoter mutants linked to the chloramphenicol acetyltransferase gene revealed the existence of a region of the promoter, -771 to -384, which is responsive to RA. Gel retardation data indicated that a cell-type nuclear protein which binds to this novel element is suppressed by RA in a dose-dependent manner. This decrease coincides with a decreased steady-state level of RAR-gamma mRNA. These data strongly suggest that the EGFR promoter is regulated by RAR-gamma, which itself is under the control of RA. Other cell-specific trans-acting factors may be involved in this regulation. PMID- 1515369 TI - Altered distribution of phospholipase C-gamma 1 in benign hyperproliferative epidermal diseases. AB - Phospholipase C-gamma 1 (PLC-gamma 1) is a well characterized substrate for the epidermal growth factor receptor tyrosine kinase and has been implicated in the intracellular biochemical signaling cascade which occurs following stimulation of cells with epidermal growth factor. The in vivo localization of PLC-gamma 1 was examined by immunohistochemistry in sections of normal human skin and in skin sections from a diverse series of hyperproliferative epidermal conditions (psoriasis, seborrheic keratoses, acrochordons, and margins near second-degree burns). Immunoreactive PLC-gamma 1 was detected only in the basal compartment of normal skin but was readily detectable in both the basal and outer epidermal compartment in hyperproliferative skin conditions. In addition, immunoreactive PLC-gamma 1 colocalizes with immunoreactive epidermal growth factor receptor in both normal and hyperproliferative epidermis. PMID- 1515370 TI - Adolescent developmental change in topography of EEG amplitude. AB - EEGs were recorded from 32 channels in 30 normal males, ages 16-22. Delta activity decreased throughout this age range. This decrease was greatest in the left frontal and temporal regions; no occipital lead showed this pattern. Relative EEG amplitude analysis, based on normalized maps, revealed decreases with age across alpha, delta, and theta bands with beta staying the same or increasing. These changes were greatest in the left temporal and left frontal regions. Taken together, these findings suggest that these cortical areas are maturing in the second decade of life. Both delta and theta showed significantly greater decreases with age in the left parietal region than in the right. PMID- 1515371 TI - Mortality in DSM-IIIR schizophrenia. AB - Mortality was investigated in 356 DSM-IIIR schizophrenics admitted to a university psychiatric hospital over a 12-year period. Determination of death was made through a record-linkage process and observed death was compared with the mortality experience of the general population of the State of Iowa. Schizophrenics had nearly a three-fold increase in overall mortality. Mortality was primarily attributable to unnatural causes of death, particularly suicide, which was more than twenty-three times greater than expected. Mortality was greater in schizophrenic patients younger than 40 years and during the early portion of follow-up. Studies of mortality in psychiatric patients continue to be important, particularly as diagnostic criteria become better refined. PMID- 1515372 TI - Validity of the negative/positive dichotomy for schizophrenic disorders under long-term conditions. AB - A total of 148 patients fulfilling the DSM-III symptomatological criteria of schizophrenia were classified according to Andreasen's criteria of positive, negative and mixed symptomatology. After excluding cases of permanent hospitalisation and patients with monoepisodic course the remaining 100 patients had a total of 458 episodes. Of these episodes, 213 were identified as positive, 134 as negative and 111 as mixed. During the course of illness the proportion of negative episodes increased and the proportion of positive episodes decreased. The great majority of the patients (76%) had a bimorphous course, i.e. one showing both types of schizophrenic symptomatology, positive and negative. Only 6% of the patients had only negative episodes, and only 18% had only positive episodes. The shift from one type of episode to another is dependent on the length of illness. Stability was not greater later during the course of illness than at the beginning. PMID- 1515373 TI - Early parental death: relation to electrodermal orienting response and gender in schizophrenia. AB - The aim of the present study was to examine age at parental loss by death and its relation to electrodermal orienting response and sex in schizophrenia. Forty-four DSM-III schizophrenic inpatients were exposed to a series of moderately intense tones in a standard orienting habituation paradigm, while skin conductance was recorded. The twenty-three patients who failed to respond to any of the first two tones were found to be younger when they lost their first parent compared to the 21 responders. When the 44 patients were divided according to sex, the females were found to be younger than the males when parental loss occurred. Finally, when multivariate analyses were performed, it was found that both responding/nonresponding and sex provided almost equally large independent contribution to the prediction of parental loss. PMID- 1515374 TI - Gender and the familial risk for schizophrenia. Disentangling confounding factors. AB - Recent studies of the effect of gender on the familial risk for schizophrenia have shown that relatives of females have a higher risk for schizophrenia than relatives of males. This study attempts to explain the effect by examining factors found to differentiate schizophrenic men and women and found to be related to the familial risk for schizophrenia. Cox proportional hazard regression model was used to examine the simultaneous effects of age at onset, season of birth, and premorbid history, controlled for symptoms that have been found to differ by gender (dysphoria, paranoia, and flat affect). Results showed that the effect of gender on the transmission of schizophrenia could not be explained by gender differences in age at onset, symptom expression, premorbid history, and winter birth. However, premorbid history had an effect on familial risk independent of gender, indicating that probands with a poor premorbid history had a lower familial risk for schizophrenia than those with a good premorbid history. Implications of the findings are discussed. PMID- 1515375 TI - Prediction of employability in schizophrenic patients. AB - This study, the third of a series of reports on employability and schizophrenia, investigated the effects of both interview and non-interview variables on employability. Data on 46 chronic schizophrenic inpatients included demographic and illness-related variables, measures of psychopathology and interview-based ratings of employment skill. Latent class analysis using linear structural relations (LISREL) modelling generated the main finding namely, that interview based measures are the strongest determinants of employability. However, other variables pertaining to illness, prior functioning and negative symptoms, exert an effect on interview performance and hence indirectly influence employability ratings and judgements. PMID- 1515376 TI - Covariance of personality, neurocognition, and schizophrenia spectrum traits in the community. AB - Clinical researchers have observed in relatives of schizophrenic individuals abnormal personality traits resembling the psychopathology of schizophrenia. Further similarities have been observed in correlations between measures of brain function, including attention and executive abilities, and these personality psychopathologies. However, two methodologic factors might account for the covariation of these 'schizophrenia spectrum' personality traits and measures of brain function. Clinical selection bias (Berkson's bias) might result in subjects with overlapping conditions being more likely to be studied, and normal personality attributes could affect performance on neurobehavioral tasks. This study investigated relationships between neurobehavioral correlates of schizophrenia, clinical schizophrenia spectrum personality traits, and normal personality dimensions in the five-factor model of personality. To avoid Berkson's bias, subjects expected to have a high probability of spectrum traits were recruited from the Baltimore Epidemiologic Catchment Area Survey community sample. About 40% of the sample were found to have DSM-IIIR Schizotypal, Schizoid, or Paranoid Personality Traits or Disorders. Schizophrenia Spectrum traits showed significant associations with personality dimensions of the five factor model, particularly Openness to Experience and Neuroticism. In ordinary linear regression models, after adjustment for a number of normal personality characteristics, Schizotypal Personality Traits were still strongly associated with perseverative responses on the Wisconsin Card Sorting Test (WCST). In logistic regression models, subjects with Schizotypal, Schizoid, or Paranoid Traits differed in terms of normal personality profiles and WCST performance. PMID- 1515377 TI - Scanning eye movements in schizophrenic patients. Relationship to clinical symptoms and regional cerebral blood flow using 123I-IMP SPECT. AB - Eye movements during the Benton Visual Retention Test were examined using an eye mark recorder in 32 schizophrenic patients and 32 normal controls. The patients had significantly fewer eye fixations, longer mean duration of fixation and shorter length of mean scan path than the controls. In the patients, these eye movement parameters were significantly correlated with the negative symptom score but not with the positive symptom score on the Positive and Negative Syndrome Scale. These parameters had a significant correlation with the composite score on the Scale for the Assessment of Negative Symptoms (SANS). In particular, they were highly correlated with avolition-apathy and affective flattening or blunting scores on SANS subscales. Thus, examination of scanning eye movements seemed to be a good objective index of negative symptoms. Secondly, regional cerebral blood flow (rCBF) was examined using N-isopropyl-p-[123I]iodoamphetamine (123I-IMP) and single photon emission computer tomography in 17 of 32 patients. With regard to the relationship between the eye movement parameters and rCBF, the mean duration of fixation was negatively correlated with 123I-IMP uptake in the left superior frontal area and left basal ganglia. The mean length of the scan path was correlated with uptake in the left superior frontal area. These findings suggest that the characteristic eye movements of schizophrenic patients are likely to be related with dysfunction of the frontal-basal ganglia neural circuit. PMID- 1515378 TI - Wisconsin Card Sorting Test deficits in chronic paranoid schizophrenia. Evidence for a relatively discrete subgroup? AB - Some, although not all, researchers have reported dramatically increased numbers of perseverative responses on the Wisconsin Card Sorting Test (WCST) in schizophrenic patients compared to normal comparison subjects. The current study was designed to further explore the nature of possible WCST deficits in a group of paranoid schizophrenic patients compared to normal and psychiatric comparison subjects. In the current study, schizophrenic patients had significantly greater numbers of perserverative responses on the WCST than the comparison groups. The sample of patients with schizophrenia appeared to be characterized by a non Gaussian distribution of perseverative responses on the WCST. WCST-impaired and WCST-nonimpaired schizophrenic subgroups were compared on cognitive and symptom measures, and increased perseverative responding was associated with negative symptoms, slowed reaction time, and more hospitalizations. While additional research is necessary to further investigate hypotheses of frontal versus generalized brain dysfunction in schizophrenic patients, WCST impairment seems to be present in a clinically meaningful subgroup of paranoid schizophrenic patients. PMID- 1515379 TI - Dichotic listening in monozygotic twins discordant and concordant for schizophrenia. AB - Emotional and neutral word versions of the fused rhymed words dichotic listening test were administered to members of 18 pairs of monozygotic twins discordant for schizophrenia, 7 pairs concordant for schizophrenia, and 7 pairs of normal twins. In the discordant group, affected twins had smaller right ear advantages than did their unaffected cotwins for neutral words. The difference was completely attenuated with the presentation of emotional words or in less powerful between group comparisons that included twins concordant for schizophrenia and normal twins. It is unlikely that this finding reflects an abnormality in the lateralized representation of language, both because we did not find a correlation between handedness scores and dichotic listening scores and because emotional stimuli normalized results. The finding may reflect abnormalities in the allocation of attention for priming language centers in the left hemisphere. 'At risk' subjects, i.e., the unaffected members of the discordant pairs, did not differ significantly from normal monozygotic twins on measures of dichotic listening. PMID- 1515380 TI - Schizophrenic feature recognition deficits are independent of task criterion. AB - The present study determined the minimal exposure time (i.e., critical stimulus duration (CSD) necessary for feature registration and recognition by normals and chronic schizophrenics. Our interest was whether the longer exposure times required by schizophrenics than by normals could be attributed to an inability of schizophrenics to maintain attention when the task criteria were stringent as opposed to 'loose'. The present findings support previous findings of impaired feature recognition by chronic schizophrenics. Chronic schizophrenics' and normals' CSDs were not affected by task criterion. The consistent performance by these groups on the 'loose' and 'rigid' task criteria suggest that if attentional lapses occur then they are as likely to occur for chronic schizophrenics as for normals and they are independent of the task's criterion. It is concluded that impaired feature registration for chronic schizophrenics is a consequence of a deficit at the earliest stage of encoding. PMID- 1515381 TI - Association of schizophrenia and partial trisomy of chromosome 5p. A case report. AB - A normal balanced chromosome 5 translocation carrier (5:14) (p14.1; q32.3) produced one offspring with a 5p deletion syndrome (cri du chat syndrome) and two with a partial trisomy (one with schizophrenia and the other with refractory epilepsy). We had hypothesized that the translocation might be complex and involve 5q, overlapping with a schizophrenia associated area described by Bassett et al., (1988). Cytogenetic study, however, indicated that there was no overlap in the involved chromosome 5 trisomy for this individual with schizophrenia and the trisomic region previously described. The probands with the trisomy and the cytogenetic findings are described in this report. Alternative interpretations are suggested to explain the association of schizophrenia and chromosomal abnormalities. PMID- 1515382 TI - Chronotropic and inotropic effects of ropivacaine, bupivacaine, and lidocaine in the spontaneously beating and electrically paced isolated, perfused rabbit heart. AB - BACKGROUND AND OBJECTIVES: The purpose of this study was to compare the inotropic and chronotropic effects of ropivacaine, bupivacaine, and lidocaine in an isolated, spontaneously beating rabbit heart preparation. The ability to electrically pace the heart in the presence of local anesthetic also was examined. METHODS: Hearts were perfused with Krebs-Henseleit solution, then exposed to ropivacaine or bupivacaine at 1, 6, or 13 micrograms/ml or lidocaine at 6, 20, or 40 micrograms/ml (n = 6, each concentration). Left ventricular pressure, left ventricular dP/dt (rate of change derivation from analog waveform of the left ventricular pressure wave), pulmonary artery flow, oxygen consumption, and electrocardiogram were monitored throughout the studies. Drug exposure was for 30 minutes or until a 75% decrease in left ventricular pressure occurred. RESULTS: All preparations were exposed to 1 microgram/ml bupivacaine or ropivacaine and 6 micrograms/ml lidocaine for the full 30 minutes. At the intermediate concentrations, only one of six bupivacaine preparations (6 micrograms/ml) survived the full 30-minute exposure period, compared to six of six preparations for both ropivacaine (6 micrograms/ml) and lidocaine (20 micrograms/ml; p less than 0.05). Similar results were found with exposure to the highest concentrations of these local anesthetics. No electrocardiogram changes were observed with any of the three lidocaine concentrations or with the lowest ropivacaine and bupivacaine concentration. At the intermediate concentration, atrioventricular conduction changes were seen with bupivacaine in five of six preparations, compared to one of six ropivacaine preparations (p less than 0.05). With the high concentration, ventricular tachycardia occurred in four of six bupivacaine preparations, compared to zero of six with ropivacaine (p less than 0.05). In general, left ventricular systolic pressure, dP/dt, heart rate, and oxygen consumption were reduced during exposure to all concentrations of the three local anesthetics. The most profound effects (greater than 75% reduction) were seen with 13 micrograms/ml bupivacaine. All local anesthetics caused an increase in the voltage required to pace the hearts via the atria. With 6 micrograms/ml bupivacaine and 13 micrograms/ml ropivacaine, 50% of the preparations could not be paced via the atria; and with 13 micrograms/ml bupivacaine, none of the preparations could be paced via the atria. The depressant effects of 6 micrograms/ml bupivacaine approximated those seen with 13 micrograms/ml ropivacaine. The reductions in oxygen consumption and pulmonary artery flow were not significantly different between treatment groups. CONCLUSION: The results of this study indicate that bupivacaine is more cardiodepressant and arrhythmogenic than either ropivacaine or lidocaine. PMID- 1515383 TI - Hemodynamic effects of continuous spinal anesthesia: a comparative study between low and high doses of bupivacaine. AB - BACKGROUND AND OBJECTIVE: Arterial hypotension is a major side effect of spinal anesthesia. Continuous spinal anesthesia may allow titration of the amount of local anesthetic to obtain a level that is appropriate for the surgical procedure. METHODS: This study compared the hemodynamic effects and the quality of analgesia of spinal anesthesia performed with 3 ml of either 0.125% (n = 12) or 0.5% (n = 13) plain bupivacaine in 25 elderly patients undergoing orthopedic surgery. RESULTS: The initial dose's duration of action (time elapsed between the end of injection and the first patient's complaint of pain during surgery) was shorter in the group receiving 3 ml of 0.125% plain bupivacaine than in the group receiving 0.5% plain bupivacaine: 80 +/- 31 minutes versus 114 +/- 37 minutes, respectively (mean +/- SD; p less than 0.05). In 6 (50%) of 12 patients of the 0.125% group and in 2 (15%) of 13 of the 0.5% group, analgesia became insufficient during the surgical procedure, necessitating injection of an additional 1 ml (top-up) of the previous solution. All subjects obtained good anesthesia for the entire procedure. The mean dose of bupivacaine necessary for the procedure was significantly lower in the 0.125% group (4.8 +/- 1.3 mg) compared with the 0.5% group (16.1 +/- 3 mg). For a similar maximal upper level of analgesia (T4-T12 in the 0.125% group versus T2-T10 in the 0.5% group), the decrease in systolic arterial pressure was more pronounced in the 0.5% group than in the 0.125% group during the period 15-40 minutes after induction of spinal anesthesia (p less than 0.05%). The mean dose of ephedrine was threefold larger in the 0.5% group than in the 0.125% group. CONCLUSION: Continuous spinal anesthesia with small amounts of 0.125% plain bupivacaine produces effective anesthesia for orthopedic procedures in elderly patients with minimal hemodynamic changes. PMID- 1515384 TI - Failure of phenylephrine to prolong isobaric bupivacaine spinal anesthesia in elderly patients. AB - BACKGROUND AND OBJECTIVES: The effects of phenylephrine on the duration of spinal anesthesia produced by plain bupivacaine were investigated in a double-blind study of 100 elderly patients. METHODS: Each patient received a basic solution of 3 ml 0.5% plain bupivacaine to which was added either 1 ml physiologic saline, 0.2 ml (1 mg) 0.5% phenylephrine plus 0.8 ml normal saline, 0.4 ml phenylephrine plus 0.6 ml normal saline, 0.6 ml phenylephrine plus 0.4 ml normal saline, or 0.8 ml phenylephrine plus 0.2 ml normal saline. RESULTS: The duration of sensory block (measured by two- and four-segment regression times and times to regression to T12 and L2 dermatomes) was not statistically prolonged by addition of phenylephrine. CONCLUSION: It is concluded that, in an attempt to prolong plain bupivacaine spinal anesthesia, the addition of phenylephrine does not appear to be advantageous for routine clinical practice. PMID- 1515385 TI - The addition of epinephrine to subarachnoid administered hyperbaric bupivacaine with fentanyl for cesarean delivery: the effect on onset time. AB - BACKGROUND AND OBJECTIVES: This study examines the effect of epinephrine on the time to achieve a T4 sensory level when added to a hyperbaric bupivacaine fentanyl mixture for spinal anesthesia. METHODS: Sixty-nine healthy parturients scheduled for elective cesarean delivery were randomly assigned to three groups. All patients were given 9 mg hyperbaric 0.75% bupivacaine with 25 micrograms fentanyl. Group 1 received no epinephrine while Groups 2 and 3 received 100 micrograms and 200 micrograms epinephrine, respectively. Injection of the spinal anesthetic solutions was performed with the patient in the sitting position. Immediately after drug administration, patients were placed supine with their heads elevated on a pillow and 15 degrees of left uterine displacement was maintained. Vital signs and sensory levels were obtained every minute for 10 minutes. RESULTS: In Groups 2 and 3, the mean time to T4 sensory level was significantly longer (6.9 minutes and 6.6 minutes, respectively) than in Group 1 (4.6 minutes). As a subset, patients weighing more than 90.8 kg achieved a T4 sensory level faster than did those weighting less than 90.8 kg (3 minutes and 5.1 minutes, respectively), but in both groups epinephrine prolonged the onset time to T4 (5.8 minutes and 7.3 minutes, respectively). Three patients were excluded because of failure to obtain a T4 sensory level. CONCLUSIONS: The onset time to T4 is related inversely to patient weight, and epinephrine (100 micrograms and 200 micrograms) delays the onset of sensory block to T4 when administered with subarachnoid hyperbaric bupivacaine-fentanyl. PMID- 1515386 TI - Effects of epidural bupivacaine or mepivacaine on somatosensory evoked potentials and skin resistance responses. AB - OBJECTIVE: The main purpose of this study was to compare the depth of neural block in lumbar epidural analgesia using either 20 mg/ml mepivacaine or 5 mg/ml bupivacaine. METHODS: Sixteen healthy patients were randomly divided to receive blindly either 17.5 ml mepivacaine (median, 15-20) or 17.5 ml bupivacaine (median, 14-20) for lumbar epidural analgesia. Afferent block was assessed by somatosensory evoked potentials (SEPs) during electrical stimulation of cutaneous sensory nerves at the T10, L1, L4, and L5 dermatomes. Efferent block was assessed by skin resistance responses (SRRs) recorded from the hand (C6), T12-L1, and foot (L5). RESULTS: Upper level of analgesia (pin-prick, cold) was T4 (T1-11) in the mepivacaine group and T4-5 (T2-9) in the bupivacaine group. In the mepivacaine group, SEPs were abolished in seven of eight cases at the T10 stimulation level and in five of eight cases at the L1 level. In the bupivacaine group, SEPs were abolished in two of eight cases at the T10 level and in three of eight cases at the L1 level. At the L4 and L5 levels, SEPs were only slightly changed in both groups. In the mepivacaine group, SRRs were completely or almost completely blocked (0-35% of control values) in all of eight cases at both the T12-L1 level and in the foot. Corresponding values for bupivacaine were six of seven and five of eight, respectively. Skin resistance responses in the foot and hand were significantly (p less than 0.05) lower in cases with abolished SEPs at the T10 stimulation level compared with those cases with preserved (although reduced) SEPs. CONCLUSIONS: Twenty mg/ml mepivacaine produces a more complete neural block than 5 mg/ml bupivacaine. The responsiveness of the afferent and efferent limbs of the nervous system was blocked in a similar manner as was shown by depression of the SEPs and SRRs. PMID- 1515387 TI - Analysis of human epidural pressures. AB - BACKGROUND AND OBJECTIVES: During performance of epidural injection, entry into the epidural space has traditionally been determined by identification of negative pressure to the advancing needle by indirect means such as hanging drop; loss of resistance to air, saline, or water; or use of a MacIntosh balloon. Confusion in the literature regarding entry pressures versus postentry (baseline) pressures and zero reference pressure was noted. METHODS: Baseline epidural pressure changes were examined using a closed system zeroed to the dorsal spine during and after injection of local anesthetics in 39 patients referred to the Pain Treatment Center, located at SUNY Health Science Center, Syracuse, New York, for epidural injections. The course of epidural pressure changes after injection and the temporal relation of epidural pressure waves to the arterial and venous wave forms were examined. RESULTS: In contrast to previous investigations, subatmospheric pressure was found in the epidural space in only one patient. Baseline pressure for all patients was 7.7 +/- 3.9 mmHg. There were significant differences in baseline pressure in patients who had undergone back surgery compared with patients who had not undergone such surgery: 11.8 +/- 3.4 as opposed to 7.0 +/- 3.5 mmHg, respectively (p less than 0.005). Three minutes after a 2-ml injection of local anesthetic into the epidural space, the pressure returned to baseline. This contrasted to the effects of a 6-ml injection, which resulted in the pressure remaining above baseline after 3 minutes. The epidural pressure wave forms more closely paralleled the radial artery wave form than the central venous pressure. CONCLUSION: Lumbar epidural pressure is greater than atmospheric pressure when referenced to zero at the dorsal spine level. PMID- 1515388 TI - The resistance of the human dura mater to needle penetration. AB - METHODS: An aneroid manometer attached to a needle during lumbar puncture for spinal anesthesia was used to record the pressure in the epidural space, and an attempt was made to define the moment the needle contacted and indented the dura mater. RESULTS: By measuring the distance the needle travelled after contact with the dura and before its actual perforation, it was determined that the dura mater indents 2-6 mm. CONCLUSION: The finding indicated that the dura mater is relatively resistant to puncture. PMID- 1515389 TI - Regional anesthesia for cataract surgery: comparison of retrobulbar and peribulbar techniques. AB - METHODS. The features of retrobulbar and peribulbar blocks were compared prospectively in 300 patients undergoing elective, ambulatory cataract surgery. Both techniques were clinically applicable, but to achieve total akinesia of the eye muscles, an additional injection was needed in 13% of the patients with retrobulbar block and in 35% with periocular block. RESULTS. In younger patients (less than 65 years), the number of injections and the volume of the local anesthetic needed to produce a total akinesia of the eye were significantly higher when compared with the elderly. PMID- 1515390 TI - Fentanyl and lidocaine versus lidocaine for Bier block. AB - BACKGROUND AND OBJECTIVES: The present study was designed to assess the efficacy of fentanyl combined with dilute lidocaine solution for intravenous regional anesthesia of the arm. METHODS: In ten volunteers, the nondominant arm was exposed to three treatments: 100 mg lidocaine, 42 ml; 100 mg lidocaine plus 100 micrograms fentanyl, 42 ml; and 100 micrograms fentanyl, 42 ml. Each subject was tested on three occasions with three or more days between experiments. Sensory and motor function was tested to determine whether the neural effects of the particular treatments differed. RESULTS: When lidocaine and lidocaine plus fentanyl results were compared, no significant differences were found. However, anesthesia, analgesia, and loss of motor function generally were less complete and slower in onset with the fentanyl alone treatment. Two subjects became nauseated after tourniquet cuff deflation when lidocaine plus fentanyl was tested, as did one subject when fentanyl was tested. CONCLUSION: Results of this and other studies indicate there is no value in adding fentanyl to local anesthetics for intravenous regional anesthesia. PMID- 1515391 TI - Hemodynamic changes associated with tourniquet use under epidural anesthesia for total knee arthroplasty. AB - BACKGROUND AND OBJECTIVES: Epidural anesthesia is administered commonly for total knee arthroplasty, a procedure using a thigh tourniquet. Tourniquet use has been associated with intraoperative hypertension and with occasional circulatory collapse after deflation. The purpose of this study was to define the hemodynamic changes in this setting. METHODS: We prospectively studied 373 consecutive patients having a total knee arthroplasty performed under epidural anesthesia, with continuous electrocardiogram and radial artery pressure monitoring. Results were analyzed using Student's t-test, correlation coefficients, analysis of variance, or chi-square analysis. Alpha was set at 0.01. RESULTS: There was a 4 +/- 11 mmHg rise in mean arterial pressure throughout the period of tourniquet application (p less than 0.001); no clinically significant hypertension occurred. After tourniquet deflation, there was a 19.2 +/- 12% reduction in mean arterial pressure, occurring within one minute. The magnitude of mean arterial pressure reduction failed to correlate with any clinical parameter other than vasopressor use. There was a small subset of patients who had a fall in heart rate and a more profound degree of hypotension after tourniquet deflation, but these patients could not be identified before tourniquet release. CONCLUSIONS: In this setting, tourniquet-induced hypertension is rare. However, hypotension after deflation is common, occurs rapidly, and correlates poorly with clinical parameters. PMID- 1515392 TI - Indirect sonographic guidance for epidural anesthesia in obese pregnant patients. AB - BACKGROUND AND OBJECTIVES: Obesity and edema frequently obscure anatomic landmarks and result in technical difficulties during epidural anesthesia administration. However, the method of indirect sonographic guidance permits identification of the midline by sagittal scan of the laminae of lumbar vertebrae 2, 3, and 4. METHODS: Thirty-six obese women scheduled for elective repeat cesarean delivery were prospectively studied. Use of a 5-MHz transducer positioned with the transducer center site over the second or third interspace allowed measurement of skin-to-lamina distance by the electronic calipers of a Toshiba SAL-32B or RT 3000 GE machine, prediction of needle depth for epidural puncture (EP), and skin marking of the site. After the transducer was removed, a 9.5- or 11.4-cm Tuohy needle was percutaneously advanced perpendicularly from the site until EP was achieved. RESULTS: Needle depth was measured by marker and measure, and epidural anesthesia was successfully administered to all patients. Simple linear regression analysis was performed with strong positive results. Indirect and continuous sonographic guidance studies designed to determine whether sonography reduces complications are planned. PMID- 1515393 TI - The concept of a conical spinal needle. PMID- 1515394 TI - Temperature, not pain, is best for assessing regional block. PMID- 1515395 TI - Labeling of bupivacaine solutions. PMID- 1515396 TI - Minimizing the risk of needle sticks during spinal anesthesia administration. PMID- 1515397 TI - 3-in-1 or 4-in-1? PMID- 1515398 TI - In defense of the 3-in-1 block. PMID- 1515399 TI - Glucosamine oligomers: 4. Solid state-crystallization and sustained dissolution. AB - When glucosamine oligomers are stored in the solid state they undergo a process of crystallization. The extent to which this occurs depends on whether the samples are isolated in the -NH3+ or -NH2 form, on the storage time, and on the degree of polymerization of the isolated oligomer. The allomorph obtained by this process seems to correspond to the so-called 'tendon-chitosan'. Dissolution of such aged oligomer samples gives rise to a process of dissociation of the associated chains in the crystal, leading to the establishment of a pseudo equilibrium between single and associated oligomer chains and hence the simultaneous presence of the 'monomeric', 'dimeric', 'trimeric', etc., forms of the oligomer. The phenomenon cannot be attributed to a process of aggregation in solution. The effects of various parameters on this behaviour have been investigated. PMID- 1515400 TI - Limited proteolysis of streptokinase and properties of some fragments. AB - Limited proteolysis of streptokinase (Sk) by trypsin and thermolysin was performed under various incubation conditions and analysed by polyacrylamide gel electrophoresis. Several fragments (Sk1, Tr27, Tr17, Th26, and Th16) were isolated and characterized further. The N-terminal sequences of Tr27, Tr17, Th26, Th16 and the C-terminal sequences of Tr27 and Th26 were determined by partial sequencing. The evidence available allows the positioning of these fragments within the Sk sequence. Fragment Sk1 is obtained by carefully standardized tryptic digestion of Sk and gel chromatography under non-denaturing conditions. Sk1 is formed by a large polypeptide Ser60-Lys293 and non-covalently bonded smaller polypeptides composed of amino acids from the N-terminal region Ile1 Lys59 of Sk. Fragment Tr27 consists of the large polypeptide Ser60-Lys293 of Sk1, and can be obtained from Sk1 by removal of the smaller N-terminal polypeptides under denaturing conditions. Fragment Th26 is composed of amino acids Phe63 His291. The N-termini of fragments Tr17 and Th16 start with Glu148 and Ile151. From their electrophoretically-determined sizes it can be concluded that they most probably have the same C-terminal amino acids, Lys293 and His291, as fragments Tr27 and Th26, respectively. Secondary structure elements of similar composition were found in all the fragments studied using circular dichroism (c.d.) and infrared (i.r.) measurements. Differential scanning calorimetric (d.s.c.) measurements were performed in order to correlate the sequence regions of Sk to energetic folding units of the protein. Fragments Sk1, Tr27, Th26, Tr17, and Th16 show one melting peak in the temperature range from 42.8 to 46.1 degrees C (thermal unfolding stage). For fragment Sk1, this melting peak can be separated by deconvolution into two transitions at T1 = 46.1 degree C and T2 = 47.3 degrees C with delta H1 = 450 kJ/mol and delta H2 = 219 kJ/mol, respectively. Fragments Tr17 and Th16 show one two-state transition at T = 42.8 degrees C with delta H = 326 kJ/mol. PMID- 1515401 TI - Biosynthesis of poly(3-hydroxyalkanoates) from threonine. AB - A series of copolyesters of 3-hydroxybutyrate (3HB) and 3-hydroxyvalerate (3HV) was biosynthesized by Alcaligenes eutrophus from an amino acid, threonine. The 3HV content of these polyesters ranged from less than 0.1% to 30%. PMID- 1515402 TI - Cross-linking and gel formation of water-soluble lysine polypeptides. An insolubilization model reaction for adhesive proteins. AB - Insolubilizing studies of water-soluble synthetic polypeptides containing lysine residues were examined using organic aliphatic and aromatic cross-linking agents such as dialdehydes, diacyl chlorides and diactive ester, together with an enzyme tyrosinase, in water and simulated seawater systems. The cross-linking reaction was characterized by the viscosity and turbidity changes. Among the organic cross linking agents used aliphatic glutaraldehyde and aromatic o-phthalaldehyde were the most effective. When excess organic cross-linking agents were added to the lysine polypeptide systems, the corresponding solid gels were formed. As a whole, the molecular weight of the samples, the amino acid compositions, the cross linking agent used, the molar ratios between cross-linking agents and functional residues and system pH were found to have roles in the insolubilizing reaction and the gel formation. The cross-linking results obtained were compared with those of the polypeptide-tyrosinase systems, whose deep brownish red colour was decolorized by the addition of L-ascorbic acid. PMID- 1515403 TI - Branched-chain analogues of linear polysaccharides: a spectroscopic and conformational investigation of chitosan derivatives. AB - The solution properties and conformational features of 2-substituted propanoic acid (I) and 2-substituted pentanedioic acid (II) derivatives of chitosan were investigated over a wide range of pH by potentiometric, optical and chiroptical measurements, and by theoretical conformational analysis. No significant change is observed in the solution properties of I upon pH variations, in agreement with computational results showing that the conformational features of the polymer do not vary with respect to the charge state of the ionizable groups. In contrast, spectroscopic titration and preliminary 1H-n.m.r. data indicate that conformational equilibria in II are pH-dependent. Consistently, computed models show that both the charge state of the ionizable groups and the chirality of the carbon atom in the side chain control the structural features of the polymer. PMID- 1515404 TI - Biosynthesis and n.m.r. studies of deuterated poly(3-hydroxybutyrate) produced by Alcaligenes eutrophus H16. AB - Alcaligenes eutrophus H16 was grown on mixtures of 1H- and 2H-acetate as carbon sources. The accumulation of deuterated poly(3-hydroxybutyrate) (P(3HB)) was observed. The deuterium distributions in the isolated P(3HB)s were determined from 1H and 2H-n.m.r. spectra and confirmed by 13C-n.m.r. spectra. Although one would expect to synthesize P([2,2,4,4,4-2H5]3HB) when the cells were grown on 2H acetate as the sole carbon source, the methyl, methylene and methine groups of the P(3HB) contained both deuterium and proton. This observation indicates some substitution from 2H to 1H during the P(3HB) synthesis. The 2H content in the methyl groups was larger than that in the methylene groups, which suggests a kinetic isotope effect in the P(3HB) synthesizing process. The deuterium distributions in the two magnetically non-equivalent methylene protons were determined to be different, which indicates stereoselectivity at the C2 site. PMID- 1515405 TI - Molecular and crystal structure of (1----3)-alpha-D-glucan triacetate. AB - A crystal and molecular structure for GTA I, the low temperature polymorph of (1- --3)-alpha-D-glucan triacetate, is proposed on the basis of X-ray diffraction analysis of well-oriented films, combined with stereochemical model refinement. The unit cell is monoclinic with parameters a = 30.17 A, b = 17.42 A, c (fibre axis) = 12.11 A, and beta = 90 degrees C. The probable space group is P2(1) with b axis unique. Six molecular chains pass through the unit cell with alternating polarity and with three independent chains comprising the asymmetric unit. The chain axes are located in a hexagonal packing arrangement. The chain backbone conformation is a left-handed, three-fold helix, but all nine O(6) acetyl groups of the asymmetric unit are in non-equivalent rotational positions. The most probable structure is indicated by X-ray residuals R = 0.261 and R" = 0.283, based on 62 reflection intensities (41 observed and 21 unobserved). PMID- 1515407 TI - Does American science need Russian humanitarian aid? PMID- 1515406 TI - The variability of cardiopulmonary adaptation to pregnancy at rest and during exercise. AB - OBJECTIVE: To examine the cardiopulmonary adaptation to normal pregnancy in sitting women during rest and bicycle exercise. DESIGN: A longitudinal study beginning early in pregnancy and ending 8-12 months after delivery. SETTING: University Hospital, Zurich, Switzerland. SUBJECTS: 20 women were monitored every second week during pregnancy from 8 to 14 weeks gestation, twice in the puerperium and twice 6-8 weeks and twice 8-12 months after delivery. All the women finished the study, but not all of them participated in every visit. MEASUREMENTS AND MAIN RESULTS: The results obtained 8-12 months after delivery are considered the non-pregnant data and are presented first so that any change in pregnancy will be more obvious. Values given below refer to the median except when stated otherwise. At rest: 1. Oxygen consumption increased significantly from a median of 182 ml/min in the non-pregnant state to 256 ml/min by 8-11 weeks gestation, and peaked at 300 ml/min at 32 weeks. At 6-8 weeks after delivery the value was 225 ml/min. 2. Oxygen consumption per kg increased significantly from 3.0 ml/min in the non-pregnant state to 4.3 ml/min by 8-11 weeks gestation and peaked at 5.0 ml/min soon after delivery. At 6-8 weeks after delivery the value was 3.4 ml/min. 3. Carbon dioxide production generally showed changes similar to those of oxygen consumption. 4. Respiratory quotient did not show any significant changes. 5. Ventilation increased from a median of 9.4 l/min in the non-pregnant state to 10.5 l/min by 8-11 weeks and then slowly increased to 12.6 l/min in late pregnancy. 6. Respiratory rate did not change significantly. 7. Tidal volume showed a median of 563 ml in the non-pregnant women and rose significantly to 632 ml in early pregnancy, peaking at 715 ml in late pregnancy. 8. Alveolar ventilation increased significantly from a non-pregnant value of 3.4 l/min to 6.2 l/min in early pregnancy, peaking at 6.7 l/min at term; 6-8 weeks after delivery the value was 4.5 l/min. 9. Ventilation equivalent for oxygen fell significantly from the median non-pregnant value of 52 to 42 in early pregnancy and remained at that level until 6-8 weeks after delivery when it was 44. 10. Ventilation equivalent for carbon dioxide showed similar changes to those for oxygen. 11. Alveolar carbon dioxide tension fell significantly from a median non-pregnant level of 4.6 kPa (34 mmHg) to 4.0 kPa (30 mmHg) in early pregnancy. It began to increase in the puerperium and was 4.3 kPa (33 mmHg) 6-8 weeks after delivery. 12. Mixed venous carbon dioxide tension fell significantly from a median of 5.9 kPa (44 mmHg) to 5.2 kPa (39 mmHg) during pregnancy. 13. Transcutaneous carbon dioxide tension decreased significantly in early pregnancy from 8.8 kPa (66 mmHg) in the non-pregnant women, and from 20 weeks gestation remained at 6.9 kPa (52 mmHg). 14. Transcutaneous oxygen tension showed a non-significant increase from 10.0 kPa (75 mmHg) in the non-pregnant women to 11.1 kPa (83 mmHg) during pregnancy. 15. Cardiac frequency increased gradually from a non-pregnant median of 80 b.p.m. to about 90 b.p.m. in the last 2 months of pregnancy. In the puerperium the median was 75 b.p.m. 16. Cardiac output increased significantly by almost 50% from the non-pregnancy level to that at 8-11 weeks gestation. 17. Cardiac output per kg also increased significantly by 50% from the non-pregnant level to that at 8-11 weeks gestation. From mid-pregnancy there was a gradual fall until delivery. 18. Stroke volume increased significantly from a median of 31 ml in the non-pregnant state to 51 ml in early pregnancy, and remained at this level until delivery. In the puerperium the stroke volume was 63 ml. 19. Oxygen pulse increased significantly from a median of 2.2 ml in the non-pregnant women to 3.1 ml in early pregnancy and remained at that level. 20. Individual curves.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1515408 TI - A possible way out of the current quagmire in research funding. PMID- 1515409 TI - Assembly and transport of MHC class II molecules. AB - At the surface of antigen-presenting cells MHC class I and class II molecules present peptides to respectively CD8+ and CD4+ T cells. MHC class I molecules acquire peptides right after synthesis in the endoplasmic reticulum. MHC class II molecules do not acquire peptides in the endoplasmic reticulum but instead associate with a third chain, the invariant chain which impedes peptide binding. Subsequently the invariant chain takes MHC class II molecules to the endosomal/lysosomal compartment thanks to a targeting signal retained in its cytoplasmic tail. It then dissociates from the MHC class II dimer to allow it to bind peptides. PMID- 1515410 TI - Proline isomerases at the crossroads of protein folding, signal transduction, and immunosuppression. AB - The immunosuppressants cyclosporin A (CsA), FK506, and rapamycin block T-cell activation by interfering with signal transduction. The institution of CsA therapy for prophylaxis against graft rejection revolutionized human organ transplants, and clinical trials with FK506 and rapamycin are in progress. The targets for these drugs, cyclophilin for CsA and FKBP for FK506 and rapamycin, are members of two unrelated families of ubiquitous, highly conserved, abundant proteins. Although unrelated, both cyclophilin and FKBP catalyze proline isomerization and may fold proteins. The structures of both cyclophilin and FKBP have been determined, in some cases in complex with drugs or substrates. The cyclophilin-CsA and FKBP-FK506 complexes prevent T-cell response to antigen, bind and modulate the activity of the protein phosphatase calcineurin, and prevent nuclear import of a subunit of NF-AT, a T-cell activation transcription factor. In contrast, rapamycin blocks T-cell responses to IL-2. Yeast genetic studies suggest that the FKBP-rapamycin target is a protein complex involved in cell cycle progression. Further studies should provide fundamental insights into T cell activation, signal transduction, and protein folding, and hold the promise of more specific immunosuppressive therapies. PMID- 1515411 TI - Dynamics of the Dictyostelium cytoskeleton during chemotaxis. AB - Movement and chemotaxis are fundamental processes of cells and tissues and are based on the dynamics of the cytoskeleton. The cellular slime mold Dictyostelium discoideum is an excellent model system with which to study the molecular components and the key reactions that are required for a coordinated locomotion of single cells or a cell mass during development. The D. discoideum cytoskeleton relies mainly on the equilibrium between monomeric and filamentous actin and, like other nonmuscle cells, contains a large number of actin-binding proteins that either decrease or increase the rigidity of the microfilament system. The proteins themselves are regulated by phosphorylation, Ca2+, phospholipids, and/or pH and thus are targets for the intracellular changes that occur upon stimulation of a cell with chemoattractant. In a synopsis of the data published during the past years, the properties of numerous cytoskeletal components and the biochemical reactions of the signal transduction chain are combined here in a schematic model that attempts to explain how the directed movement of a cell could be coordinated at the molecular level. PMID- 1515412 TI - Antisense strategies come of age. Antisense strategies sponsored by the New York Academy of Sciences, Philadelphia, PA, USA, January 12-15, 1992. PMID- 1515413 TI - Signal transduction cascade shared by epidermal growth factor and platelet derived growth factor is a major pathway for oncogenic transformation in NRK cells. AB - We have isolated two recessive, mutually complementary NRK cell mutants that are refractory to transformation by epidermal growth factor (EGF) and transforming growth factor-beta. Both mutants are defective in a signal transduction cascade shared by EGF and platelet-derived growth factor (PDGF). Analysis of the mutants suggests that transformation of NRK cells by the v-fms, v-erbB, activated erbB-2, v-ras, v-fos, v-mos, v-fes, v-src, SV40 large T, polyomavirus middle T, and human papillomavirus type 16 E6,E7 oncogenes is mediated by the EGF/PDGF signal cascade. The data also suggest that the EGF/PDGF cascade branches into mitogenic and oncogenic signals, the latter of which is required for soft agar growth and focus formation. PMID- 1515414 TI - Oncogenic signal-induced ability to enter S phase in the absence of anchorage is the mechanism for the growth of transformed NRK cells in soft agar. AB - Upon neoplastic transformation, cells acquire the ability to grow in soft agar. We investigated how this occurs by cell cycle analysis of a rat cell line NRK-49F and its transformation-deficient mutants. Rapidly growing NRK and mutants arrest in G1 when deprived of anchorage by suspending in methylcellulose. Addition of epidermal growth factor (EGF) together with transforming growth factor-beta (TGF beta), which is highly oncogenic to NRK, induces the rapid progression of G1 arrested NRK cells into S phase. The time course and the extent of synchronization are very similar to the cell cycle progression in the presence of anchorage. EGF alone, which is highly mitogenic but only slightly oncogenic, fails to induce such progression. Both mutants remain arrested in G1. These data indicate that oncogenic signals confer on NRK the ability to enter S phase in the absence of anchorage and that this is the principal mechanism for its ability to grow in soft agar. PMID- 1515415 TI - Analysis of the DNA binding and transcriptional activation properties of the Ets1 oncoprotein. AB - The c-ets1 gene product (Ets1) is the prototype of a family of sequence-specific transcriptional activators which have been implicated in various developmental processes and in the response of cells to a variety of extracellular stimuli. We report here a structure-function analysis of the DNA binding and transcriptional activation properties of Ets1. The minimal region required for specific DNA binding is located at the carboxy-terminus of Ets1, a domain highly conserved in all known members of the Ets family. Transcriptional activation by Ets1 in mammalian cells requires an additional domain of 110 amino acids characterized by a high content of acidic residues and localized in the amino-terminal half of the protein. This domain also functions as a transcriptional activation domain in yeast cells when linked to the heterologous DNA binding domain of Gal4. In contrast to its conservation in Ets1 proteins across vertebrate species, this activation domain is not conserved in other members of the Ets family. These results indicate that an important level of specificity between different members of the Ets family may reside in the differential interactions of their respective activation domains with distinct general transcription factors or different associated coactivators. PMID- 1515416 TI - Context rules of rightward overlapping reading. AB - We have investigated the mechanism and sequence context rules governing ribosome frameshifting promoted by aminoacyl-tRNA limitation. In the case of one shifty sequence, frameshifting promoted by lysyl-tRNA limitation occurs at the sequence AAG C and is due to rightward movement of the ribosome so as to read the AGC triplet overlapping the hungry codon from the right. The frequency of this event is unaffected by sequence elements more than three bases to the left (upstream) or two bases to the right (downstream) of the hungry codon, and only slightly affected by the identity of the base two bases to the right. It is strongly affected by the base immediately to the right of the hungry codon, which becomes the wobble base of the shifted triplet; and by the third base of the hungry codon, even though the two synonyms (AAG and AAA) call for the same aminoacyl tRNA; and by the identity of the base immediately to the left of the hungry codon. The latter result suggests that the aminoacyl-tRNA in the P site affects the maintenance of reading frame at the adjacent A site of the ribosome. However, the DNA sequence makes it seem unlikely that the P-site tRNA shifts to the right in concert with the A-site tRNA, a mechanism that can account for leftward frameshifting (in the opposite direction) in retroviral translation. The specificity of sequence determinants of leftwing versus rightwing frameshifting is discussed. PMID- 1515417 TI - Regulation of HTLV-I gene expression by tax and AP-2. AB - The HTLV-I transactivator protein tax activates expression of both viral and cellular genes. In addition it has been demonstrated to repress expression of the DNA beta-polymerase gene. We wished to investigate potential interactions between tax and the cellular transcription factor AP-2 which binds to distinct motifs in each of the three 21-bp repeat sequences in the HTLV-I LTR. First we demonstrate that AP-2 is capable of activating HTLV-I gene expression. Cotransfection experiments reveal that AP-2 and tax are capable of inhibiting each other's ability to activate HTLV-I gene expression. The mechanism of this inhibition was studied by gel retardation analysis using both bacterial and in vitro synthesized AP-2 and tax proteins. These results indicate that tax inhibits the ability of AP 2 to bind to the 21-bp repeat. Mutational analysis of both tax and AP-2 demonstrate that the amino termini of both proteins are potential sites of interaction. These results are consistent with a model in which AP-2 and tax can potentially form protein complexes resulting in an altered ability of each factor to modulate HTLV-I gene expression. PMID- 1515418 TI - Activation in vivo of the minimal replication origin beta of plasmid R6K requires a small target sequence essential for DNA looping. AB - The plasmid R6K contains three distinct origins of replication: alpha, beta, and gamma. The gamma sequence is essential in cis and acts as an enhancer that activates the distant alpha and beta origins. R6K therefore represents a favorable procaryotic model system with which to unravel the biochemical mechanisms underlying selective origin activation, particularly activation involving distant sites on the same chromosome. We have discovered that plasmids containing the origins alpha and gamma required the Escherichia coli DnaA initiator protein in addition to the R6K-encoded initiator protein, Pi, and other host replisomal proteins for their maintenance in vivo. Plasmids initiating replication from origin beta required only the Pi initiator protein and other host replisomal proteins. We have exploited the differential requirement for the DnaA protein by origins gamma and beta to selectively study and localize the minimal origin beta sequences by deletion analysis as one test of a looping model of origin activation. A 64-bp region spanning the extreme -COOH terminal coding sequence of the Pi protein was found to be essential for replication in vivo in the absence of DnaA protein, consistent with the approximate physical location of the beta origin. Replication emanating from origin beta could be abolished in vivo by deletion of the 9-bp target site for Pi protein-mediated DNA looping between the gamma origin/enhancer and the distant beta origin. Electron microscopy of nascent replication intermediates generated in vivo directly confirmed our genetic localization of the beta origin. Our results strongly suggest that activation of the beta origin by a distant replication enhancer element requires a small target sequence essential for initiator protein-mediated DNA looping. PMID- 1515419 TI - In situ lacZ retrovirus-marked lymphocytes define a B cell microenvironment in the lymph node medulla. AB - A recombinant nonreplicating retroviral vector bearing the Escherichia coli lacZ indicator gene was used to mark a population of B cells in situ in murine lymphoid tissue. The retrovirus was surgically injected into popliteal lymph nodes during the primary immune response to DNP-CGG when B cell proliferation in the germinal centers was maximal. LacZ+ cells were initially detected in the perivascular medullary interstitium, where they expanded and persisted up to 2 weeks following retrovirus injection. Migrant lacZ+ B cells were detected in the spleen 3-18 weeks following immunization and resided in the red pulp or marginal zones. Two-color flow cytometric analysis using a fluorogenic substrate for beta galactosidase revealed that lacZ+ cells bear kappa light chains and that at least 50% of these cells bound the hapten, DNP. Based on their location, life span, migratory capacity, antigenic specificity, and surface immunoglobulin density, lacZ+ cells define a distinct nonfollicular B cell population associated with other late developmental stages of B lymphocytes, including memory and plasma cells. PMID- 1515420 TI - Effects of recombinant human interleukin-1 alpha on clonogenic growth of primary human tumors in vitro. AB - Interleukin-1 alpha (IL-1 alpha) is a low-molecular-weight cytokine that regulates proliferation and differentiation of lymphatic and myeloid cells. It also has pleiotropic activity on a variety of other target cells and acts as an important mediator of inflammation and septic shock. Recombinant human IL-1 alpha (rhIL-1 alpha) is undergoing clinical evaluation of its potential as an anticancer agent. We have studied the growth modulating effects of rhIL-1 alpha on a variety of freshly explanted human tumor specimens using an in vitro soft agar cloning system. Final concentrations of 0.01-100 ng/ml were used in continuous incubation experiments. Of 139 specimens tested, 56 (40%) were evaluable for determination of tumor growth modulating activity. The most common tumor types examined included breast, nonsmall cell lung, ovarian, colorectal cancer, and melanoma. Stimulation of tumor colony-forming units (colony formation greater than or equal to 1.5 x controls) was observed in only 1/56 (2%) tumors. No evidence was found for increased size of individual colonies after incubation with rhIL-1 alpha. At a concentration of 100 ng/ml, colony formation of 9/56 (16%) tumor specimens was significantly inhibited (colony formation less than or equal to 0.5 x controls). We conclude that rhIL-1 alpha is not a major modulator of tumor colony formation in vitro. However, some antitumor effects may be observed at high concentrations. PMID- 1515421 TI - In vitro and in vivo effects of recombinant human interleukin-2 in naive miniature swine. AB - Recent data in mice have shown that early administration of recombinant human interleukin-2 (rIL-2) provides significant protection from lethal graft-versus host disease. Because of the potential clinical importance of these findings, it will be important to assess the effectiveness of this therapy in a large animal preclinical bone marrow transplantation model. We report here our initial studies of the in vitro and in vivo effects of rIL-2 in miniature swine. In vitro 4-day cultures of pig peripheral blood lymphocytes (PBL) in complete medium containing rIL-2 at 1,000 U/ml resulted in optimal proliferation and generation of lymphokine-activated killer (LAK) cells. A pig-mouse hybridoma cell line was found to be highly sensitive as a LAK cell target. Two naive pigs received 20,000 U/kg and 2 pigs received 100,000 U/kg of rIL-2 intravenously twice a day for 4 days. No clinical symptoms were seen during or after administration at the lower dose while both high dose-treated animals showed generalized erythema from days 2 to 4, and one showed mild diarrhea during this period. The disappearance of IL-2 activity from the serum showed two components: (1) an initial fast component with a half-time of approximately 10 min and (2) a slow component with a half-time of approximately 60 min. LAK cell precursors disappeared from the peripheral circulation by 6 min after rIL-2 administration and began to recover by 6 h in the low dose recipients and only after 12 h in the high dose recipients.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1515422 TI - A Southwest Oncology Group Phase I study of the sequential combination of recombinant interferon-gamma and recombinant interleukin-2 in patients with cancer. AB - Thirty-seven patients with advanced malignancies were treated sequentially with recombinant interferon-gamma (rIFN-gamma) and recombinant interleukin-2 (rIL-2) in an outpatient dose escalation clinical trial. rIFN-gamma (0.1 or 0.25 mg/m2/day) was administered by intramuscular injection, days 1-7 and rIL-2 (12, 18, or 24 x 10(6) IU/m2/day) was administered by a 15-min intravenous bolus, days 8-12. Common toxicities encountered included fever, chills, fatigue, neutropenia, and elevations of SGOT, bilirubin, or creatinine. Hypotension and cardiac and pulmonary toxicities were rare. With repeated cycles of therapy, nausea/vomiting and diarrhea associated with the administration of rIL-2 were seen in greater frequency. There were no treatment-related deaths, and no patient required intensive care unit admission for toxicity management. A complete response was observed in one of 11 patients with renal cancer and a partial response was observed in one of seven patients with malignant melanoma. Due to problems with drug supply, further dose escalation could not be continued, and maximum tolerated doses (MTD) were not determined by strict criteria. However, the combination of rIFN-gamma, 0.25 mg/m2/day, and rIL-2, 24 x 10(6) IU/m2/day, appeared to be beyond the MTD, as three of six patients at this dose level could not complete one cycle of therapy due to toxicity. It is unlikely that higher doses of either agent would be tolerated, and for further study using this schedule, we recommend the doses: rIFN-gamma, 0.1 mg/m2/day, and rIL-2, 24 x 10(6) IU/m2/day. PMID- 1515423 TI - Renal cell carcinoma treated with continuous-infusion interleukin-2 with ex vivo activated killer cells. AB - High-dose recombinant interleukin-2 (rIL-2) results in tumor responses in patients with metastatic renal cell carcinoma ranging from 9 to 31%. Continuous infusion regimens of rIL-2 may be less toxic and may result in greater in vivo lymphokine-activated killer (LAK) cell production. The current trial used a continuous infusion of rIL-2 with ex vivo LAK cells. These cells were pretreated with phenylalanine methyl ester to remove monocytes to allow cell culture at higher concentrations. Twenty-three patients were entered into the trial. Two patients had complete responses (9%) lasting 15+ and 20+ months. Four patients had partial responses (17%) of 9+, 6+, 3, and 3 months, respectively. One partial responder at 9+ months had only minimal residual retroperitoneal disease that may represent scar tissue. All responders had prior nephrectomies. All but one of the responding patients completed a full cycle of rIL-2 at the highest (starting) dose, 6 x 10(6) U/m2. This rIL-2/LAK regimen appears to be an effective therapy for metastatic renal cell carcinoma. PMID- 1515424 TI - Enhancement of lymphokine-activated killer activity induction in vitro by interleukin-1 administered in patients with urological malignancies. AB - We have evaluated the synergistic effects of interleukin-1 (IL-1) and interleukin 2 (IL-2) on the induction of lymphokine-activated killer (LAK) activity. Subcutaneous injection of recombinant IL-1 beta at an initial dose of 1 x 10(4) U was given to nine patients (five with renal cell carcinoma, two with bladder carcinoma, one with renal pelvic tumor, one with testicular tumor) on days 1 and 2 weekly for 4 weeks. The dose was increased weekly up to 4 x 10(4) U, if it was well tolerated. Peripheral blood mononuclear cells (PBMC) were isolated from patients on day 3 in the 2nd and 4th weeks, and LAK activity of PBMC against Daudi cells was measured using a 4-h 51Cr-release assay at an effector:target cell ratio of 20:1, after incubation with 50 U/ml of recombinant IL-2 for 72 h. Proliferation of PBMC was measured by tritiated thymidine incorporation after incubation with IL-2 for 72 h. IL-2 receptor (IL-2R)-positive cells in PBMC were enumerated using monoclonal antibody and flow cytometry. Mean values of LAK activity induced by IL-2 were significantly augmented after administration of IL 1 beta (p less than 0.01). IL-1 beta, however, did not enhance proliferation of PBMC caused by IL-2, nor did it increase the number of IL-2R-positive cells in peripheral blood lymphocytes of the patients. Results suggest that combination of IL-1 and IL-2 has synergistic antitumor activity in treatment of malignant diseases. PMID- 1515425 TI - Adoptive immunotherapy with activated macrophages grown in vitro from blood monocytes in cancer patients: a pilot study. AB - Ninety-three collections of leucocytes by cytapheresis followed by separation of monocytes by centrifugal elutriation were undertaken in twelve metastatic cancer patients (four melanomas, six colon carcinomas, one ovarian carcinoma, and one lung cancer). The leucaphereses were performed aiming to collect a product, ready for introduction into the elutriation chamber, i.e., with low contamination by erythrocytes and granulocytes. The median collection of leucocytes was 7.3 x 10(9). After elutriation, purified monocytes (mean: 0.91 x 10(9)) were cultured with 3-5% autologous serum for 7 days in the presence of 250 IU/ml of recombinant human gamma-interferon (Rh-IFN gamma) for the last 18 h of culture. The median number of activated macrophages (MAK) available for reinfusion was 2.4 x 10(8) for each culture. The phenotypes and the antitumoral potentiality of MAK cells were documented. Reinfusions performed i.v. or i.p. were well tolerated with no major side effects. No complete tumor response was obtained. One partial response and two stabilizations of the disease were observed in one melanoma and two colon carcinomas. PMID- 1515426 TI - Interleukin-2 in association with increasing doses of interferon-gamma in patients with advanced cancer. AB - Twenty-seven patients with evaluable metastatic cancer were treated with recombinant interleukin-2 (rIL-2) and escalating doses of interferon gamma (IFN gamma). rIL-2 was infused over a 15 min period at a constant dose (8 x 10(6) IU/m2/8 h x 5 days first cycle, and 8 x 10(6) IU/m2/12 h x 5 days second and third cycles, with 9 days rest between each cycle). IFN-gamma was started 4 days before each cycle of rIL-2 and was given every other day at a dosage of 1 x 10(6) U/m2 x 3/cycle (four patients), 5 x 10(6) U/m2 x 3/cycle (four patients), 5 x 10(6) U/m2 x 5/cycle (four patients) and 10 x 10(6) U/m2 x 5/cycle (15 patients). Common side effects were fluid retention and hepatic toxicity (27 and 15% grade greater than or equal to 2); one ischemic chest pains and one acute respiratory distress occurred. Toxicities were not greater than those described with high dose rIL-2 alone and were similar in each dose level of IFN-gamma. No patient died from the procedure. Four patients responded, one complete response and three partial responses; all were treated with 25 or 50 x 10(6) U/m2/cycle of IFN-gamma (melanoma, two patients; renal cell carcinoma, one patient; lymphoma, one patient). Further phase II studies at these dosages are justified to precisely define the antitumoral efficacy of this association. PMID- 1515427 TI - Reversible cardiomyopathy after high-dose interleukin-2 therapy. AB - We observed two patients who developed moderate global myocardial dysfunction during therapy with high-dose interleukin-2 (IL-2). Although cardiac enzymes became markedly elevated at the completion of a full course of IL-2, patients exhibited no ischemic symptoms. Serial echocardiography documented global myocardial dysfunction, which resolved in 5 days in one patient but persisted beyond 4 weeks in another. Asymptomatic reversible myocardial injury can occur with high-dose IL-2 and can persist beyond 4 weeks after stopping therapy. Review of the literature suggests an IL-2-associated myocarditis as an etiology. PMID- 1515428 TI - Quality of nursing worklife issues--a unifying framework. AB - This article describes a theoretical view of the many variables that influence nurses' worklife. It summarizes the national perspective and the provincial initiatives undertaken during the last decade that focus on issues of nursing worklife. The authors present a model that unifies the many dimensions that must be examined in studying this important problem. Nurse administrators will find this review valuable as a guide to research and practice initiatives associated with quality of working life. PMID- 1515429 TI - The economic crisis and nursing. AB - As Federal and Provincial governments wrestle with the economic crisis, Ministries of Health in every province are frantically and systematically introducing actions and major reforms to curb escalating health care expenditures. The reforms that are being introduced with an alarming speed are less of a threat to nurses than they are to doctors. The impending battles over professional turf will ultimately shape the nature and design of the new systems. This crisis constitutes an opportunity for nurses to become engaged in the reform process and thus shape the health care delivery system to their advantage. PMID- 1515430 TI - Overview of nursing research in health care within the current economic context. AB - This is an overview of nursing research findings in the following areas: forecasting the need for nursing personnel; evaluating the effectiveness of nursing care; and, costing nursing services. The author suggests the models for forecasting the need for nursing person power require further development and should incorporate more of the multitude of intricate factors that impact on nursing and the demands for care. Research in nursing case costing, workload measurement systems and the cost effectiveness of nursing care are also addressed in leading to the conclusion that there is an urgent and timely need for more nurse researchers to examine all of these complex nursing issues in relation to the whole health care system and thus be ready and in position to influence health policy and costs. PMID- 1515431 TI - Utilization review and management: a primer. AB - URM, HIS, HMRI, DRG's, CMG'S, RIW's, etc. At the fall 1990 National Congress on Utilization Review and Management in Edmonton, Dennis Psutka referred to these as "alphabet soup". It is probable that many front line managers find many of these terms and abbreviations confusing, if not overwhelming. Intended as a primer, this manuscript will: define the key terms and concepts in utilization review and management; explain their interrelationships; and discuss why it is important for nurse managers to understand and use them, as the entire health care system struggles to achieve more with fewer resources. PMID- 1515433 TI - Nursing economics in Canada. PMID- 1515432 TI - On job sharing. PMID- 1515434 TI - Overview of health care restructuring within current resources. PMID- 1515435 TI - Legal aspects of organ transplantation: an overview of European law. PMID- 1515436 TI - Mechanical circulatory support and heart transplantation. AB - Mechanical circulatory support systems are currently in clinical use to keep patients alive with the aim of either cardiac recovery after open heart surgery, myocardial infarction and after heart transplantation with acute graft failure, or as a bridge to transplantation in heart transplant candidates. At the German Heart Institute the "Berlin Heart" mechanical circulatory support system has been used invariably since 1987. Up to 1991 there were 22 patients in the "recovery" group. Four patients could be weaned from the system, but only one patient was discharged from the hospital. In 65 patients mechanical circulatory support systems were implanted as a bridge to transplantation, 39 patients had transplants, and 22 patients left the hospital. Risk factor analysis in the bridging group revealed that previous heart surgery, infective pneumonia, shock related coagulation disorders, and an age greater than 50 years had an unfavorable influence on patient survival. It is concluded that patients may be kept alive for weeks and months after any kind of cardiogenic shock. Complete cardiac recovery may be achieved in the case of early posttransplant graft failure. Reliable prediction of outcome in the bridge to transplantation group requires further experience. PMID- 1515437 TI - Bridging to transplant: allogeneic heart transplantation after xenografting. AB - Xenografting seems to be a solution to use to bridge time intervals when desperately needed allograft cannot be obtained. A following allograft was never ventured. Nine dogs (weight, 20 to 25 kg; age, 2 years) underwent right cervical heart transplantation. Donors were silver foxes (3 to 4 kg). The animals were treated by triple-drug therapy consisting of cyclosporine, methylprednisolone, and azathioprine in clinical dosages. For control, six recipients received only allogeneic hearts and the identical immunosuppression. After rejection of the xenograft, a second allogeneic heart was anastomosed subsequently to the same right cervical vessels. Routine histologic and immunohistologic examinations were performed. Thromboxane B2 and 6-keto-prostaglandin F1 alpha were determined daily in peripheral blood. After final rejection the sensitization of the recipient was controlled by hemagglutination test. Survival time of the xenografts was 9.6 +/- 1.2 days; the subsequent allogeneic hearts under the same therapy beat for 4.5 +/ 5.0 days. The average survival time of control hearts was 18 +/- 1.9 days. The five hyperacute second allografts showed signs of humoral rejection by absence of inflammation. The release of thromboxane B2 was different in hyperacute, accelerated, or cellular rejection. In contrast to the long-functioning grafts, thromboxane B2 persisted during hyperacute rejection at a high level. However, 6 keto-prostaglandin F1 alpha showed no significant differences between longtime survivors and hyperacute rejecting hearts. After xenogeneic transplantation, all recipients showed hemagglutinating titers between 1:4 and 1:16. Allogeneic grafts have a different kinetics of rejection after xenogeneic heart transplantation compared with control hearts. Thromboxane B2 seems to be an important mediator in hyperacute rejection.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1515438 TI - Cardiomyoplasty to improve myocardial collateral blood supply as an alternative to transplantation in intractable angina. AB - In diffuse small-vessel coronary heart disease, heart transplantation may be indicated for intractable angina. As an alternative, a free striated muscle flap can constitute a source of neovessels. Those extraintracardial collaterals develop only 4 weeks after transplantation of the flap as shown by the following experiments with seven dogs. In those animals a myocardial infarction of the anterior wall was selectively produced by the Judkins technique for the injection of Sephadex microspheres. Four weeks later a free pectoralis muscle flap was transplanted onto the anterior wall of the heart. Arterial blood supply was achieved by anastomosis with the internal mammary artery. The venous flow was directed into the right atrium. Six weeks after surgery the patency of the anastomosis was studied by angiography, which showed patency in all animals. Pathologic examination of the hearts revealed a prominent capillary network penetrating into the underlying myocardium. Corrosion cast preparations showed even further penetration of the capillary network into the noninjured parts of the myocardium. Thus myocardial revascularization could be achieved by transplantation of a skeletal muscle on the heart. PMID- 1515439 TI - The meta-physiology of organ preservation. PMID- 1515440 TI - Heart transplantation, euthyroid sick syndrome, and triiodothyronine replacement. PMID- 1515441 TI - Size matching in heart transplantation. AB - After heart transplantation, problems may arise from hearts that are either too small or too large. Although the "classic" rule requires that the donor/recipient weight ratio mismatch measure not less than 0.8, the chronic organ shortage led to a challenge of that margin. In selected cases donor/recipient weight mismatches of up to 0.5 may be accepted. In these circumstances, heterotopic heart transplantation may be an alternative. In pediatric heart transplantation, disproportionately large hearts (donor/recipient weight mismatches of 2.0 to 3.0) may create the so-called "big-heart syndrome," with coma and general convulsions. Treatment consists of peripheral pressure control with nifedipine. PMID- 1515442 TI - Size matching in lung transplantation. AB - Volume concordance between donor lungs and the chest cavities of transplant recipients has important perioperative and postoperative implications. Between December 1987 and August 1991, 90 patients underwent lung transplantation in the Joint Marseilles-Montreal Lung Transplantation Program: 51 patients had double lung transplants, 19 patients had single lung transplants, and 20 patients had heart-lung transplants. There were 18 children (age range, 7 to 17 years) and 72 adults (age range, 18 to 58 years). Size matching was based on measurement of the submammary thoracic perimeter. Patient age (+/- 2 years) was also taken into consideration in children. Airway anastomoses were bronchial except for all heart lung transplant patients and two double lung transplant patients, who had tracheal anastomoses. Occasional differences between donor and receiver bronchial diameters in children (greater donor size twice and smaller donor size once) required bronchoplasty in three instances. Healing was normal in these three instances, and no bronchial stenoses were noted. Performance of separate sutures rather than continuous running sutures on the cartilaginous anterior portion facilitated correction of airway diameter inequalities in adults. Excess volume was noted in three patients during closure of the thorax. In one patient, donor and recipient thoracic perimeters were similar. In two patients, however, donor size was greater by more than 20%. This was corrected by pneumoreduction with a surgical stapler. Lung size was decreased by 10% to 40% with use of this technique. Thoracic closure was facilitated and hemodynamic instability was thus corrected. No functional abnormalities were noted after surgery once the differences in lung size were corrected.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1515443 TI - Influence of interrupted pulmonary lymph drainage on antibody responses in hilar stripped lungs. AB - Lung transplantation interrupts hilar lymphatics. This may have an impact on immune responses to antigens entering the lung because the antigens cannot reach the lung-associated lymph nodes where the immune response is generated. We investigated the interruption and regeneration of lymphatics and the influence of this on antibody responses after hilar stripping in rats in three experiments: (1) visual detection of regenerated hilar lymphatics by chromolymphography, (2) observation of transport of carbon particles from the lung to the lung-associated lymph nodes, and (3) assessment of antibody responses after lung immunization with sheep red blood cells. The findings showed that hilar lymphatics were interrupted by hilar stripping and regenerated from day 7 after operation. Transport of particles to the lung-associated lymph nodes was blocked during the first week after operation but returned to normal values thereafter. Serum antibody titers were absent or low in the rats immunized on days 7 and 10 after hilar stripping; subsequently antibody responses gradually recovered in 1 month. We conclude that antibody responses to antigens in hilar-stripped lungs are impaired as long as the antigens cannot be transported through lymphatics from the lung to the lung-associated lymph nodes. These findings can explain in part why pulmonary infections occur so frequently in the initial weeks after lung transplantation. PMID- 1515444 TI - Noninvasive methods of rejection diagnosis after heart transplantation. AB - For clinical follow-up and prognosis in heart transplant patients, it is important to understand accurately the presence and extent of cardiac allograft rejection. Since the introduction of endomyocardial biopsy, almost 40 different noninvasive diagnostic procedures for the recognition of myocardial rejection have been proposed. However, endomyocardial biopsy is invasive and not suitable for frequent monitoring. If the pattern of rejection shows a focal distribution, false-negative results can be expected. Discrepancies between biopsy findings and allograft function are obviously possible. State-of-the-art information will be given on the most reliable noninvasive methods for rejection diagnosis, which can be differentiated from electrophysiology (fast-Fourier-transformed electrocardiography and intramyocardial electrocardiography), echocardiography, immunologic methods (cytoimmunologic monitoring, transferrin receptors, and interleukin-2 receptors), various biochemical markers (neopterines, prolactin, urinary polyamines, and beta 2-microglobulins), radioisotopic techniques (antimyosin-monoclonal antibodies, thallium, technetium, and gallium scintigraphy and indium-labeled cells), as well as magnetic resonance imaging. Thus modified and patient-adapted antirejection therapy can be provided if the decision for or against antirejection therapy is not based on biopsy findings alone but rather is confirmed along with histologic, electrophysiologic, biochemical, immunologic, and functional parameters. PMID- 1515445 TI - Exercise physiology and rehabilitation after heart transplantation. PMID- 1515446 TI - Medium-term results of heart and lung transplantation. PMID- 1515447 TI - Causes of exercise limitation after heart-lung transplantation. AB - A decade after the first successful human heart-lung transplantation and with improved recipient survival, there is now a growing interest in the quality of life achieved after this procedure. Patients undergoing heart-lung transplantation suffer from diseases that are most protracted and uniformly fatal. Before surgery, they are usually debilitated from the primary disease and long-term inactivity. Therefore several factors contribute to the maximal work capacity achievable after transplantation. They are principally unavoidable complications of allograft transplantation, mainly lung rejection, but include the toxic effects of immunosuppressant therapy. Many, however, are a function of the prolonged incapacitation and deconditioning imposed by the pretransplant illness. The relative roles of these factors in limiting posttransplant exercise tolerance in the various disease groups undergoing heart-lung transplantation are discussed. PMID- 1515448 TI - Accelerated graft coronary artery disease: diagnosis and prevention. AB - Accelerated graft coronary artery disease (CAD) has become a major factor limiting survival among long-term heart transplant survivors. Currently 14%, 37%, and 50% of patients treated with triple therapy have angiographically apparent accelerated graft CAD at 1, 3, and 5 years after transplantation. Because cardiac allografts are denervated, transplant recipients generally do not experience angina pectoris. Therefore accelerated graft CAD may present as silent myocardial infarction, congestive heart failure, or ventricular arrhythmia leading to syncope or sudden death. Noninvasive tests for CAD have been insensitive for the detection of accelerated graft CAD because of the diffuse nature of the disease. Coronary arteriographic characteristics of accelerated graft CAD are a mixture of typical focal atherosclerotic lesions and unusual diffuse, concentric, and longitudinal narrowing prominent in middle to distal coronary vessels, with distal vessel obliteration and lack of collateral vessel formation. The presence and severity of accelerated graft CAD may be underestimated by routine angiography because of its diffuse and concentric nature. Quantitative arteriography has become an important technique to assess the progression of accelerated graft CAD. Intravascular ultrasound imaging can detect even earlier development of intimal thickening. CAD risk factor modification has had little impact on the overall incidence. We initiated a randomized study of diltiazem versus no calcium blocker to determine if this may prevent accelerated graft CAD. Patients have undergone early postoperative and annual quantitative coronary angiography since inception of the study.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1515449 TI - Pediatric heart transplantation: issues relating to outcome and results. The Loma Linda University Pediatric Heart Transplant Group. PMID- 1515450 TI - Lung transplantation in children. PMID- 1515451 TI - Adapted indications for lung transplantation: discussion report. PMID- 1515452 TI - Molecular basis of apparent isolated 17,20-lyase deficiency: compound heterozygous mutations in the C-terminal region (Arg(496)----Cys, Gln(461)--- Stop) actually cause combined 17 alpha-hydroxylase/17,20-lyase deficiency. AB - The molecular defect in a reported case of isolated 17,20-lyase deficiency in a 46XY individual has been elucidated. The patient was found to be a compound heterozygote, carrying two different mutant alleles in the CYP17 gene. One allele contains a point mutation of arginine (CGC) to cysteine (TGC) at amino acid 496 in exon 8. The second allele contains a stop codon (TAG) in place of glutamine (CAG) at position 461 in exon 8 which is located 19 amino acids to the carboxy terminal side of the P-450(17) alpha heme binding cysteine. COS-1 cells transfected with cDNAs containing one or the other of these mutations showed dramatically reduced 17 alpha-hydroxylase and 17,20-lyase activities relative to cells transfected with the wild type P-450(17) alpha cDNA. While the in vitro data in COS 1 cells can explain the patient's physical phenotype, with female external genitalia, it was somewhat discordant with the clinical expression of isolated 17,20-lyase deficiency with relative preservation of 17 alpha hydroxylase activity in vivo. In addition to the expression studies of these two examples of mutants in the C-terminal region of cytochrome P-450(17) alpha, a third mutant cDNA construct containing a 4-base duplication at codon 480 previously found in patients with combined 17 alpha-hydroxylase/17,20-lyase deficiency was also expressed in COS-1 cells. This expressed protein was completely inactive with respect to both activities, supporting the biochemical findings in serum and in vitro biochemical data obtained using a testis from the patient. The results from these patients clearly indicate the importance of the C terminal region of human P-450(17) alpha in its enzymatic activities. PMID- 1515453 TI - Identification of five rare mutations including a novel frameshift mutation causing beta zero-thalassemia in Thai patients with beta zero thalassemia/hemoglobin E disease. AB - 6 out of 14 uncharacterized beta-thalassemia alleles from 187 Thai beta thalassemia/HbE patients were identified by direct sequencing of DNA amplified by polymerase chain reaction. A novel mutation occurring from an insertion of adenosine in codon 95, which results in a shift of the reading frame with terminator at the new codon 101, was detected in one patient. In addition, two frameshift mutations not previously reported among the Thai population were also detected in 3 patients: one with a deletion of thymidine in codon 15 and two with an insertion of cytidine in codons 27/28. A frameshift mutation that occurred from a cytidine deletion in codon 41 was also found in one patient in this study. The remaining case was an amber mutation, GAG-TAG, in codon 43 in exon 2 of the beta-globin gene. These mutations bring the number of mutations known to be present in the Thai population to a total of 20, 15 of which were detected in beta-thalassemia/HbE patients. PMID- 1515454 TI - Cleavage of type VIII collagen by human neutrophil elastase. AB - In this report, the susceptibility of type VIII collagen to human neutrophil elastase is compared to other extracellular matrix components. Type X collagen is degraded to specific fragments at a substrate to enzyme ratio of 5:1 after 20 h at room temperature, but type VIII collagen is almost completely degraded after only 4 h incubation at a substrate to enzyme ratio of 50:1 and partly degraded after only 15 min. Laminin, merosin and types I, III, IV and V collagen exhibit no susceptibility to neutrophil elastase under the latter conditions, while fibronectin is degraded. PMID- 1515455 TI - Purification and identification of a CD25 expression inhibitory protein from cell free supernatants of chronically HIV-infected promonocytic cells. AB - The CD25 (IL-2-R alpha) cell surface glycoprotein expressed transiently during T cell activation is implicated in the high affinity IL-2 receptor. This paper shows that cell-free supernatants from chronically HIV-infected promonocytic cells spontaneously produce a soluble factor which inhibits CD25 expression on PHA-activated human PBMC. We purified the CD25 expression inhibitory activity by a factor 12,350, using XM50 ultrafiltration, Superose 12 molecular sieving chromatography and MonoQ anion-exchange chromatography. Then we associated this activity to one single spot (M(r) 29,000, pI 6.8) on an O'Farrell two-dimensional gel. Our data demonstrate that this protein (M(r) 29,000, pI 6.8) is released from HIV-infected promonocytic cells and suggest that this factor is a new monokine regulating the T-cell activation process. PMID- 1515456 TI - Sequencing of the variant thyroxine-binding globulin (TBG)-San Diego reveals two nucleotide substitutions. AB - Thyroxine-binding globulin (TBG) is a liver glycoprotein that transports thyroid hormone in serum. In 1989, a variant TBG was reported with reduced binding affinity for thyroxine (T4) and triiodothyronine (T3) which results in low serum T4 and T3 levels. This variant, TBG-San Diego (TBG-SD), also displays reduced heat stability but has a normal isoelectric focusing pattern. We now report the sequence of the entire coding region of TBG-San Diego. It reveals two nucleotide substitutions: one located in exon 1 which results in the replacement of the normal Ser-23 (TCA) with threonine (ACA) and the other, located in exon 3, changes the normal codon 283 of TTG (leucine) with that of TTT, (phenylalanine). Allele specific amplification was used to search for both nucleotide substitutions in four affected members of the family. Results confirmed the co segregation of these nucleotide substitutions with the TBG-SD phenotype. The substitution in codon 283 has been previously described and exists as a polymorphism in some ethnic groups or in combination with other TBG variants with different physical characteristics. Thus, it appears that the replacement of Ser 23 with threonine is responsible for the observed alterations in physical properties of TBG-San Diego. PMID- 1515457 TI - L-dopa binding sites in rodent melanoma cells. AB - Rapid, saturable, specific and stereoselective binding of L-dopa to crude membranes and purified nuclei from rodent amelanotic melanoma cells is reported. Cross-linking of [3H]dopa to melanoma cell surface emphasized proteins of approx. 55, 30, 25 and less than 20 kDa. It is suggested that these binding sites may regulate melanocyte activity. PMID- 1515458 TI - Identification of O-methyldopa in the ventricular fluid of patients with Parkinson's disease. AB - A newly developed liquid chromatographic system with a multiple electrode detector was used for quantification of neurochemical substances in ventricular fluid of patients with Parkinson's disease. During the analysis, an unknown peak was observed at almost the same high-performance liquid chromatography retention time as 5-hydroxytryptophan. Through the use of ion suppression techniques, voltammographic analysis and fast atom bombardment mass spectrometry, the compound was identified as O-methyldopa, the major metabolite of L-dopa. PMID- 1515460 TI - High-performance anion-exchange chromatography coupled with mass spectrometry for the determination of carbohydrates. AB - Methodology has been developed to couple high-performance anion-exchange chromatography (HPAE) with mass spectrometry utilizing the ion spray liquid chromatography/mass spectrometry (LC/MS) interface. Anion micro-membrane suppression (AMMS) has been used to remove the high concentrations of NaOH and NaOAc (10-400 mM total [Na+]) necessary for the separation of mixtures of monosaccharides and oligosaccharides. Post-suppressor addition of CH3CN/H2O solutions containing NH4OAc or LiOAc provided low-nanomole detection of the monosaccharides by selected ion monitoring of the cationized adducts. Maltooligosaccharide mixtures (three to seven residues) were separated and detected by the HPAE/AMMS LC/MS system in the full-scan mode. Low declustering potentials (35 V) in the LC/MS API source afforded intact singly and doubly charge ammoniated and diammoniated adducts of the sugars. Higher declustering potentials (65 V) produced abundant fragmentation of the ammoniated adducts. The corresponding lithiated and dilithiated species produced intact molecule ion species at higher declustering potentials. The endo H-released oligomannose species from RNase B were determined by the HPAE/AMMS LC/MS system as ammoniated adducts and resulting fragment ions with a high declustering potential (95 V) in the full-scan mode. PMID- 1515461 TI - [The connection of medical indicators with oscillations in the natural gravitational field]. AB - The hourly amount of 3140 hospital deaths, 2220 births by terminated labours, and 617 investigations of some elementary functions of haemodynamics and external respiration are correlated with tidal gravitation cycles calculated at the same time of day. The statistical analysis revealed significant dependence of the obtained data on local geometrical properties of 12-hour lunar tidal waves. Their distinctive signs were convexity-concavity and growing-sinking which the 12-hour lunar wave into 4 intervals. To each interval corresponded specific patterns of death and birth curves during 24-hours and divergent distribution of values of haemodynamics and external respiration. The investigation results and literature data point to the fact that periodic fluctuations of natural gravitation fields carrying the information on changes in space-time may serve as an outside time marker (Zeitgeber) of biological rhythms. PMID- 1515459 TI - Primary sequence confirmation of the beta-amyloid peptide from hereditary cerebral haemorrhage with amyloidosis (Dutch type) by collisional activation of the doubly charged ion. AB - High-energy collisional activation of doubly charged peptide ions allows direct sequential analysis of peptides over 4 kDa, including leucine/isoleucine determinations. This technique was used to verify the sequence of an intact beta amyloid peptide associated with hereditary cerebral haemorrhage with amyloidosis Dutch type (4.2 kDa), which resists both enzymatic digestion and Edman sequencing. Additionally, this approach shows promise for the primary sequence confirmation of a wide variety of large peptides by tandem mass spectrometry. PMID- 1515462 TI - [The effect of gravity flow changes on the periodicity of functional activity of canine adrenal cortex and thyroid glands]. AB - Among the universal environmental factors changes of the gravity flow are not enough investigated. Relations between the dog corticoadrenal and thyroid glands functional rhythms and the properties of curvature level surfaces of the gravity flow changes were established. The suggested mechanism of the effect of gravitation flow changes includes ability of cells and ultrastructures to reflect the geometric properties of the local space. PMID- 1515463 TI - Photoactivation of toxin conjugates. AB - A novel photocleavable protein cross-linking reagent has been used for conjugation of the ribosome-inactivating protein pokeweed antiviral protein from seeds of Phytolacca americana (PAP-S), with either the monoclonal antibody 5E9 directed against the human transferrin-receptor or the B-chain of ricin that binds to cell-surface oligosaccharides bearing terminal D-galactose residues. When irradiated with near-UV light (350 nm), the linker of these conjugates undergoes photolytic degradation, resulting in the release of native toxin that is fully functional. The cytotoxicities of these 5E9-PAP-S and ricin B-chain-PAP S conjugates for HeLa cells could be enhanced by irradiating the cells with light after they had internalized the conjugates. PMID- 1515464 TI - Convenient synthesis of bifunctional tetraaza macrocycles. AB - A convenient synthesis of 4-nitrobenzyl-substituted macrocyclic tetraamines and their conversion to bifunctional poly(amino carboxylate) chelating agents is described. Cyclization of (4-nitrobenzyl)-ethylenediamine with appropriate BOC protected amino disuccinimido esters in dioxane at 90 degrees C resulted in the formation of 12- and 14-membered ring diamides in 40% and 44% yield, respectively. A 12-membered macrocyclic triamide was also prepared in 44% yield by cyclization of N-(2-aminoethyl)-4-nitrophenylalaninamide with disuccinimidyl N (tert-butoxycarbonyl)iminodiacetate. Deprotection (HCl/dioxane) and reduction with borane gave the substituted macrocyclic amines which were then alkylated with either bromoacetic acid or tert-butyl bromoacetate. Preparation of the isothiocyanate derivatives and 14C labeled chelating agents are described. Attempts to prepare a 9-membered macrocyclic diamide using this cyclization technique resulted instead in a 20% yield of a 10:1 mixture of isomeric fused 5,6 ring acylamidines. Deprotection (HCl/dioxane) and reduction with borane gave a substituted piperazine derivative in 55% yield. PMID- 1515465 TI - Structure-function relationships in indium-111 radioimmunoconjugates. AB - Conjugates formed by reaction of monoclonal antibody B72.3 with benzyl isothiocyanate derivatives of four amino polycarboxylate chelators (NTA, EGTA, EDTA, DTPA) were labeled with indium-111 and administered iv to athymic mice bearing antigen-positive (LS174T) and antigen-negative (A375) human tumor xenografts. Conjugate immunoreactivities, antibody dose, and xenograft size were controlled, so that the effects of varying chelate structure could be evaluated under conditions where immunological and physiological factors were effectively held constant. Tissue distribution and excretion of the radiometal at 24 and 48 h postinjection were shown to correlate directly with chelate thermodynamic stability (NTA less than EGTA less than EDTA less than DPTA). Radioactivity levels in the blood and the LS174T xenograft increased, while kidney levels and excretion levels decreased, with increasing chelate stability. The kidney was the only normal organ that accumulated non-antibody-bound 111In, uptake of radioactivity into all other tissues, and in particular the liver, being unaffected by changes in chelate structure. Mean transferrin saturation in the tumor-bearing athymic mice was found to be 65%. It is proposed that uptake of free 111In by serum transferrin is precluded in this model, leading to the observed renal localization of unbound label. Kidney:blood and kidney:LS174T activity ratios at 48 h postinjection provided the most sensitive indices of conjugate instability in vivo, spanning 50- and 20-fold ranges, respectively, between the least stable and the most stable conjugate. It is concluded that this antigen/antibody system and mouse model are well-suited to structure-function studies of immunoglobulin labels. PMID- 1515466 TI - Conjugation and evaluation of 7E3 x P4B6, a chemically cross-linked bispecific F(ab')2 antibody which inhibits platelet aggregation and localizes tissue plasminogen activator to the platelet surface. AB - A bispecific F(ab')2 monoclonal antibody which recognizes both the platelet GPIIb/IIIa receptor and human tissue plasminogen activator was produced to target tPA to platelets for enhancement of thrombolysis. A stable, thioether-cross linked bispecific F(ab')2 (7E3 X P4B6) combining the GPIIb/IIIa-specific monoclonal antibody 7E3, which inhibits platelet aggregation, and a nonneutralizing anti-tPA monoclonal antibody (P4B6) was produced. This was performed by coupling each of the parental Fab' moieties with the homobifunctional cross-linker bis(maleimido methyl) ether (BMME). 7E3 X P4B6 was sequentially purified using gel-filtration chromatography and hydrophobic interaction (HIC) HPLC. HIC was shown to completely resolve each of the parental F(ab')2 species from the bispecific one. 7E3 X P4B6 was shown to retain completely each of the parental immunoreactivities in GPIIb/IIIa and tPA binding EIA's. The bispecific antibody inhibited platelet aggregation in vitro at levels comparable to those for 7E3 Fab. Recruitment of tPA activity to washed human platelets was demonstrated using the S-2251 chromogenic substrate assay. 7E3 X P4B6 recruited 12-fold more tPA to the washed platelets than a mixture of the parental F(ab')2 molecules used as controls. PMID- 1515467 TI - Site-specific modification of a fragment of a chimeric monoclonal antibody using reverse proteolysis. AB - We propose a novel method for the site-specific labeling of antibodies under mild conditions and give as an example the modification of an F(ab')2-like fragment of the chimeric monoclonal antibody B72.3. The F(ab')2-like fragment was produced by the action of the protease lysyl endopeptidase. Reverse proteolysis, catalyzed by the same enzyme, was then used to attach carbohydrazide specifically to the carboxyl termini of the heavy chains of the fragment. Finally, a radiolabeled chelator possessing an aldehyde group was conjugated to the modified fragment through a hydrazone linkage. The resulting site-specifically labeled F(ab')2-like fragment was characterized by gel electrophoresis and by enzymic digestion. It was found to possess immunoreactivity equivalent to that of the unmodified F(ab')2-like fragment as determined by immunofluorescence and ELISA (enzyme linked immunosorbent assay) techniques. The advantages and disadvantages of this labeling method, which appear to be of quite general applicability, are discussed. PMID- 1515468 TI - Photochemical cross-linking of guanosine 5'-triphosphate to phosphoenolpyruvate carboxykinase (GTP). AB - Mammalian phosphoenolpyruvate carboxykinase (PEPCK) specifically requires a guanosine or inosine nucleotide as a substrate; however, the structural basis for this nucleotide specificity is not yet known. Because affinity labels derived from guanosine have not yielded a stable, modified peptide in quantities sufficient for sequence analysis, we have investigated the utility of direct photochemical cross-linking of GTP to PEPCK in order to identify the nucleotide binding site. UV irradiation at a distance of 2 cm by a Mineralight lamp (330 microW/cm2) results in the attachment of [alpha-32P]GTP to PEPCK via a stable, covalent linkage in a reaction that is dependent upon GTP concentration and duration of irradiation. After 10 min of irradiation, more than 0.2 mol of [alpha 32P] GTP is incorporated per mole of PEPCK; under these conditions the GTP concentration required for half-maximal labeling is 69 microM. The substrates phosphoenolpyruvate, ITP, and GDP provide protection against photolabeling, as do Mn2+ and Mg2+. One major and one minor radioactive peptide derived from proteolytic digests of photolabeled PEPCK have been isolated and identified. The major modified peptide has been provisionally assigned to an acidic region near the C-terminus, and the minor peptide has been identified as Ser462-Lys471. PMID- 1515469 TI - Vinylstannylated alkylating agents as prosthetic groups for radioiodination of small molecules: design, synthesis, and application to iodoallyl analogues of spiperone and diprenorphine. AB - The preparation and synthetic utility of p-toluenesulfonate esters of (E)- and (Z)-3-(tri-n-butylstannyl)-prop-2-en-1-ol as bifunctional reagents for radioiodination are described. These vinylstannylated alkylating agents are prepared in two steps from propargyl alcohol, and readily couple with nucleophilic functionality (amide nitrogen, secondary amine, tertiary alcohol) in good yields (48-95%) to provide derivatives of the neuroreceptor ligands spiperone and diprenorphine. Regio- and stereospecific radioiododestannylation with retention of configuration occurs under mild, no-carrier-added conditions to give the corresponding radiolabeled N- or O-iodoallyl analogues in good radiochemical yields (55-95%) with high specific radioactivities. The methodology is versatile and well-suited to selective labeling of small molecules with radioisotopes of iodine such as 125I or 123I. PMID- 1515470 TI - Monoclonal antibody-beta-lactamase conjugates for the activation of a cephalosporin mustard prodrug. AB - Cephalosporin mustard (CM) was designed as an anticancer prodrug that could be activated in a site-specific manner by monoclonal antibody-beta-lactamase conjugates targeted to antigens present on tumor cell surfaces. Purified beta lactamases from Bacillus cereus (BC beta L) and Escherichia coli (EC beta L) catalyzed the release of phenylenediamine mustard (PDM) from CM through a fragmentation reaction which occurs after the beta-lactam ring of CM is hydrolyzed. The Km and Vmax values were 5.7 microM and 201 mumol/min per mg for BC beta L and 43 microM and 29 mumol/min per mg for EC beta L, respectively. Conjugates of BC beta L were prepared by combining the F(ab')2 fragments of the maleimide-substituted monoclonal antibodies L6 and 1F5 with thiolated BC beta L. The conjugates showed little loss in enzymatic activity and bound nearly as well as the unmodified F(ab')2 monoclonal antibodies to antigens expressed on the H2981 human lung adenocarcinoma cell line (L6 positive, 1F5 negative). PDM was approximately 50-fold more cytotoxic than CM to H2981 cells. Treatment of the cells with L6-BC beta L followed by CM resulted in a level of cytotoxic activity that was comparable to that of PDM. This was most likely due to activation of CM by conjugate that bound to cell-surface antigens, since pretreatment of H2981 cells with BC beta L or 1F5-BC beta L enhanced the activity of CM to a lesser extent. Thus, we have shown that CM is a prodrug, and that it can be activated with immunological specificity by a monoclonal antibody-beta-lactamase conjugate. PMID- 1515471 TI - Introduction of aliphatic amino and hydroxy groups to keto steroids using O substituted hydroxylamines. AB - (Aminooxy)butyl- and -hexylamines and alcohols were synthesized by the Ing-Manske modification of the Gabriel synthesis. The aminooxy group of these heterobifunctional spacer reagents is a far more powerful nucleophile than the amino or hydroxy group because of the oxygen atom adjacent to the amino group (alpha-effect). The aminooxy group reacts readily with keto groups while the amino or hydroxy (or other) group remains free for further reactions. These excellent heterobifunctional spacer reagents were used here to derivatize keto steroids in an alkaline alcoholic solution. Using the described, general, and easy one-step synthesis, aliphatic amino or hydroxy groups with a spacer arm have been introduced to testosterone, 6-ketoestradiol, and cortisol. PMID- 1515472 TI - Microparticle-enhanced nephelometric immunoassay with microsphere-antigen conjugates. AB - gamma-Irradiation of acrolein and other acrylic monomers allowed the synthesis of spherical polyfunctional hydrophilic microparticles in the size range of 50 to 300 nm, on which antigens (immunoglobulins G, chorionic gonadotropin hormone, prealbumin) could be covalently bound. Microsphere-antigen conjugates clustered together in the presence of specific antiserum or monoclonal antibodies and their agglutination was quantified by light-scattering measurement performed with a specially designed nephelometer. Essential factors concerning the conjugate agglutination and its quantitation (size of microsphere, amount of antigen bound on microsphere, concentration of conjugate, concentration of agglutinating reagent, angle of light-scattering observation) were successively studied. A microparticle-enhanced nephelometric immunoassay for prealbumin was finally developed as an example of application. It was based on the inhibition of the immunoagglutination of microspheres-prealbumin conjugate by free prealbumin. This prealbumin immunoassay was easy to perform (one-step assay without washing or phase separation), fast (30 min), reliable (variation coefficients ranged from 3.6% to 7.5% for within- and between-assay determination), and sensitive (1 microgram/L detected). It was correlated with conventional immunonephelometry and radial immunodiffusion (correlation coefficients, 0.98). Microparticle-enhanced nephelometric immunoassay offered many advantages over the last two methods. Its better sensitivity allowed a lower reagent consumption and a larger sample dilution (contrary to the conventional immunonephelometry, sample pretreatment and sample blank measurement were unnecessary). Its inhibition mode induced a total accuracy for sample with high analyte concentration (a risk of underevaluation in antigen excess conditions existed in all method based on a noncompetitive antigen-antibody reaction) and provided the possibility to quantify haptens.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1515473 TI - Activation of mouse macrophages by muramyl dipeptide coupled with an anti macrophage monoclonal antibody. AB - A rat IgG2a monoclonal antibody (mAb3A33) directed against the mouse Mac-1 antigen was conjugated with muramyl dipeptide (MDP) by using an intermediate polymer; under such conditions 75 MDP molecules were bound to one antibody molecule. A poly(L-lysine) polymer substituted with muramyl dipeptide and 3-(2 pyridyldithio)propionyl residues were prepared, the remaining lysine epsilon amino groups were acylated with D-gluconolactone, leading to a neutral polymer; then a few polymer conjugates were coupled to mAb3A33 via a disulfide bridge. The binding capacity of the monoclonal antibody was preserved after conjugation with MDP-polymer molecules. Mouse peritoneal macrophages, incubated for 24 h with MDP mAb3A33 conjugate became cytostatic against P815 mastocytoma cells, whereas unconjugated mAb3A33 and MDP-bound to a nonspecific rat IgG2a were ineffective. An enhancement of the cytostatic activity induced by MDP-mAb3A33 conjugate was obtained in the presence of gamma-IFN. These results show that several tens of MDP molecules can be linked to a macrophage-specific monoclonal antibody by using a neutral intermediate polymer without impairing the binding antibody capacity and that this type of MDP conjugate can efficiently activate macrophages and therefore could be the basis of the development of new antitumor therapy. PMID- 1515474 TI - Activating hydroxyl groups of polymeric carriers using 4-fluorobenzenesulfonyl chloride. AB - 4-Fluorobenzenesulfonyl chloride (fosyl chloride), due to the strong electron withdrawing property of its fluoride atom, is found to be an excellent activating agent for the covalent attachment of biologicals to a variety of solid supports (e.g. functionalized polystyrene microspheres, Sepharose beads, or cellulose rods and hollow fibers). This reagent reacts rapidly with primary or secondary hydroxyl groups, at ambient temperature and pressure, to form 4 fluorobenzenesulfonate leaving groups. The activated solid support can be used immediately or preserved for several months without loss of activity by freeze drying or by storage at 4 degrees C in aqueous solution at pH 5. Enzymes, antibodies, avidin, and other biologicals can be covalently attached to the activated solid phase with excellent retention of biological function. Potential therapeutic applications of the fosyl chloride chemistry for bioselective separation of human lymphocyte subsets from whole blood and tumor cells from bone marrow are presented. PMID- 1515475 TI - Radiolabeling of monoclonal antibodies and fragments with technetium and rhenium. PMID- 1515476 TI - Preliminary results from the self-regulatory treatment of high-medication consumption headache. AB - Data are presented from a prospective clinical replication series of ten consecutive high-medication headache patients who presented for nondrug treatment of their headaches. For the first eight, an attempt was made to withdraw the patients from medication, with the assistance of relaxation training, prior to entering a comprehensive self-regulatory treatment program. For the last two, drug withdrawal accompanied the treatment. Six of the ten patients showed clinically significant reductions in headache activity, which held up over follow ups of up to 12 months. Psychological tests provide some discrimination between success and failures. PMID- 1515477 TI - Self-regulation of slow cortical potentials in psychiatric patients: depression. AB - Findings on depressive patients indicate that depressives have electrophysiological characteristics similar to those of schizophrenics, in that they exhibit reduced Contingent Negative Variation (CNV) amplitudes and more distinct Postimperative Negative Variations (PINVs) than normal controls. In a biofeedback experiment, 8 medicated male inpatients with the DSM III-R diagnosis of "Bipolar Disorder, Depressive," and "Major Depression" demonstrated no impairment in the self-regulation of Slow Cortical Potentials (SCP) in comparison to schizophrenics in terms of increasing and suppressing negativity. Continuous visual SCP feedback is presented to the patient as a horizontally moving rocket in a video game format. The direction changes of the rocket represented SCP changes at each point in time, recorded by the central EEG (based on the pretrial baseline). Depressives demonstrated SCP self-regulation across 20 sessions, although with many between-and-within variations. The 8 male controls were unable to regulate their SCPs across 5 sessions. This result contradicts other findings of our laboratory on normal controls. Motivational factors and insufficient operant reinforcement (financial reward) may have facilitated this effect. PMID- 1515478 TI - The effects of centrally acting drugs on the EEG correlates of meditation. AB - The present study investigated the effects of three centrally acting drugs on the significant increase in the intermediate alpha frequency of the electroencephalogram (EEG) that accompanied meditation in a male volunteer. When compared to the EEG recorded before each of the three drugs was administered, naloxone tended to enhance the increase in the power of the intermediate alpha EEG (9.4-10.4 Hz), while diazepam tended to spread the increase to the slow (7.4 9.4 Hz) alpha EEG, and flumazenil was without much effect on the overall EEG pattern. However, these EEG changes when compared to similar changes obtained with saline administration were not significantly different from the latter. Thus, it is unlikely that the EEG correlates of meditation are causally related to the rise or fall of endogenous opioid peptides or benzodiazepinelike substances in the brain. PMID- 1515479 TI - Microencapsulated bovine chromaffin cells in vitro: effect of density and coseeding with a NGF-releasing cell line. AB - Immobilization of discrete cell clusters within a partially crosslinked matrix prevents reaggregation of primary tissues and may provide a means for long-term maintenance of encapsulated cells. Dissociated bovine adrenal chromaffin (BAC) cells were suspended throughout crosslinked polyanionic microspheres previously shown to be selectively permeable. Microcapsules approximately 500 microns in diameter were seeded with: 1) three different densities of BAC cells; and 2) BAC cells suspended in Matrigel or coseeded with a genetically modified nerve growth factor (NGF)-releasing fibroblast cell line. Each group was analyzed in vitro at 1, 4 and 8 weeks for spontaneous and potassium-evoked release of catecholamines, and maintained in vitro for up to 12 weeks for morphological observations. Over time, release of norepinephrine (NE) and epinephrine (EPI) diminished, while dopamine (DA) remained constant from the monoseeded capsules. In the coseeded group, an increase in potassium-evoked release of DA was observed from 1 to 4 weeks, and remained at that level up to 8 weeks. Encapsulated chromaffin cells retained a rounded morphology typical of undifferentiated cells. Intact chromaffin cells with well preserved and abundant secretory granules were observed ultrastructurally after 4 weeks in vitro. Small neurites from the chromaffin cells in the coseeded group were observed at 4 weeks with light microscopy, and up to 12 weeks with electron microscopy. Under static incubation conditions, 1 mM D-amphetamine resulted in a significant increase in the output of NE and DA from the coseeded capsules 8 weeks post-implantation, as compared to microcapsules loaded with chromaffin cells alone. Encapsulation within an immobilization matrix allows manipulation of the internal environment, thereby providing the ability to pre-treat cells with various factors in a non-invasive manner, which may enhance long-term cellular viability. PMID- 1515480 TI - Fetal brain transplantation in kainic acid lesioned caudate nucleus of adult rats. AB - This study confirmed that bilateral kainic acid (KA) injection at the caudate produces aphagia and adipsia in rats. The reduction in food and water intake was fatal after a higher dosage of the drug. To test the effect of transplantation on the mortality rate, KA was first injected in the left caudate, in one set of rats. After a gap of three days, fetal striatal tissue was unilaterally transplanted at this lesioned site, along with a second injection of KA in the right caudate. Successful transplantation, as ascertained morphologically, did not significantly alter the mortality rate. The morphometric study revealed that the neurons of the transplant were larger in size, and their numerical density lower than those of the caudate of normal rats. Only very few neurons of the transplant developed functional connectivity with the host, as demonstrated by electrophysiological studies. PMID- 1515481 TI - Estrogen receptors are present in neocortical transplants. AB - Fetal neocortical tissue was grafted into neocortical lesion cavities made in newborn rats. After two weeks survival, in vitro binding of [3H]-estradiol to cytosolic preparations provided evidence of estrogen receptors within the transplants. The observed high levels correspond to previous work demonstrating elevated estrogen receptor levels during the first postnatal week in the rat cerebral cortex. PMID- 1515483 TI - Reconstruction of brains and journals. PMID- 1515482 TI - Successful xenografts of second trimester human fetal brain and retinal tissue in the anterior chamber of the eye of adult immunosuppressed rats. AB - Successful xenografting of first trimester human fetal CNS tissue and retina has been reported in the literature. We wished to test the feasibility of using the anterior chamber of the rat eye to support the development of more mature human fetal xenografts. Here we report on the successful outcome of human brain and retinal transplants. Adult host rats immunosuppressed with cyclosporin A accepted these xenografts and supported their further development. Periodic examination of the host eyes using a direct ophthalmoscope or an ophthalmic slit lamp permitted direct visual monitoring of the health and growth of the transplants. Histologically it was possible to identify neuronal, macroglial, and microglial (macrophage) cell types within the grafts. Mitotic activity and histogenetic differentiation took place. Blood vessels filled with hematic cells were commonly present within the grafts. The walls of these vessels prevented the leakage of horseradish peroxidase, suggesting the presence of a functional brain-blood barrier in the graft. These results indicate that it is possible to use a small animal model to study normal and pathological phenomena on late fetal human neural tissues. Our group has already taken advantage of the model to achieve HIV infectivity of fetal human brain outside the human body. PMID- 1515484 TI - Viable adrenal medullary transplants in non-human primates: increasing the number of grafts. AB - The robust survival of stereotaxic adrenal medullary autografts in monkey brain parenchyma depends heavily on technique. One aspect of technique critical for clinical applications of CNS grafting is the problem of spreading treatment effects throughout large regions in a primate brain. Stereotaxic placement of a large number of grafts, which would address this problem, would require that later grafts retain the capacity for viability over a long period of time during the surgery, while earlier grafts are being made. In the present experiments involving 12 longtailed macaques (Macaca fascicularis), some grafts remained in medium 2.5 h before being transplanted, without apparent loss of viability. A clinically sufficient distribution of graft tissue would also require a large number of separate grafts to be derived from one adrenal medulla. One method for subdividing the gland might be to cut it into numerous very small pieces, but various dicing techniques described in this report have yielded little viable graft tissue. On the other hand, the number of ribbon grafts of the original dimensions available from a single gland is rather small; adrenal ribbons of the original dimensions were therefore further dissected. Half-length and half-width ribbons were successful, but less so than full-size ribbons in terms of proportionate viability. An assay of behavioral effectiveness, applied to all subjects described here, is presented in a separate contribution. PMID- 1515485 TI - Behavioral effects of adrenal medullary transplants in non-human primates. AB - Small multiple "ribbon" autografts of intact adrenal medulla stereotaxically implanted at several sites throughout the striatum in longtailed macaques (Macaca fascicularis) have been shown to contain large amounts of viable glandular tissue as long as eight weeks after transplantation. Variations of technique clearly influence viability. All monkeys were maintained in specially adapted rotometer cages so that 24-hour measurements of activity and directional bias could be gathered. Lesions induced by intracerebral injection of 6-hydroxydopamine in the substantia nigra produced the expected chronic decrease in percentage of contralateral turning in most of the 24 subjects. Animals that received the longest viable ribbon grafts showed a reversal of this effect back toward base line, whereas monkeys whose grafts left little or no surviving tissue showed no behavioral improvement. PMID- 1515486 TI - A sensitive dot immunobinding assay for serodiagnosis of African swine fever virus with application in field conditions. AB - The present work describes a simple dot immunobinding assay (DIA) for African swine fever virus (ASFV) antibody detection that can be used under field conditions. The assay uses nitrocellulose strips dotted with a cytoplasmic soluble antigen (CS-P) of ASFV. The nitrocellulose strips are adhered to a plastic handle. The test serum samples react with the CS-P, and antibodies are detected using a protein A-peroxidase conjugate. Both incubations are carried out at 20 C. The efficacy of the DIA as a screening test for ASFV was compared to an enzyme-linked immunosorbent assay (ELISA) and an immunoblotting (IB) test using 343 sera collected from natural African swine fever epizootics and from inapparent ASFV carriers. The DIA had comparable sensitivity to both reference techniques, and all samples positive in the ELISA and IB test were also positive in the DIA. False-positive reactions were not detected when whole blood or poorly preserved serum samples were tested by DIA. Some poorly preserved sera that were positive initially by the ELISA were no longer ELISA positive in a later run, although they were positive in IB and DIA. These positive DIA and IB test results could be caused by the differences in antibody epitope binding. PMID- 1515487 TI - Effect of culture media and incubation temperature on growth of selected strains of Francisella tularensis. AB - The rate and amount of growth of 4 field isolates and reference strain ATCC 6223 of Francisella tularensis were evaluated on isolation media with 2 different agar bases and with different supplements and incubated at 25 C, 35 C, and 42 C. Biochemical reactions on conventional differential media with and without cysteine were evaluated. Two of the field isolates and the reference strain were F. tularensis subspecies tularensis (formerly biovar tularensis or Type A), and 2 isolates were subspecies holarctica (formerly subspecies palaearctica or Type B). Bacto cystine heart blood agar supplemented with 1% hemoglobin, glucose cystine heart blood agar, and brain-heart infusion blood agar supported good growth of all 4 field strains, with the most luxuriant growth occurring on Bacto cystine heart blood agar with hemoglobin. Heart infusion blood agar and trypticase soy blood agar supported growth of the field isolates, although growth was diminished and delayed. Strain 6223 was distinctly fastidious and failed to grow on heart infusion or trypticase soy blood agars. Growth of strain 6223 was best on Bacto cystine heart blood agar with hemoglobin. The agar base did not affect growth unless the supplements became limiting, in which case Bacto agar base generally supported growth better than BiTek agar base. Incubation at 35 C was optimum for all 5 strains. Growth at 42 C was slow, with the greatest decrease in the rate and amount of growth occurring with field isolates of F. tularensis subspecies tularensis. Strain 6223 did not grow at 25 C, and the 4 field isolates grew slowly at the lower temperature.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1515488 TI - Pleuropneumonia caused by Actinobacillus pleuropneumoniae biotype 2 in growing and finishing pigs. AB - Actinobacillus pleuropneumoniae biotype 2 was isolated in pure culture or as the predominant isolate from the lungs of 9 growing and finishing pigs with pleuropneumonia. Gross and microscopic lesions resembled those caused by A. pleuropneumoniae biotype 1 serotypes (Nos. 1, 5, and 7) traditionally seen in the United States. The overall mortality rate for growing and finishing pigs on this 1,200-sow farrow-to-finish farm ranged from 0.37% to 0.84% per month from July 1990 to February 1991, and mortality due to respiratory disease ranged from 0.17% to 0.52% per month for the same period. This Actinobacillus species did not require V factor (no satellitism on blood agar with a Staphylococcus streak), was strongly beta-hemolytic, and demonstrated restriction fragment length polymorphisms in hybridization studies with A. suis, A. lignieresii, and A. equuli. Biochemically, the isolate most closely resembled A. pleuropneumoniae, and a DNA fragment considered specific for A. pleuropneumoniae biotypes 1 and 2 was demonstrated using polymerase chain reaction. Necrohemorrhagic pleuropneumonia similar to that caused by A. pleuropneumoniae biotype 1 was reproduced experimentally in 2 4-week-old pigs inoculated intratracheally with broth cultures of the A. pleuropneumoniae biotype 2. This study demonstrated the presence of A. pleuropneumoniae biotype 2 in the United States. PMID- 1515489 TI - Prevalence and serovars of leptospira involved in equine abortions in central Kentucky during the 1990 foaling season. AB - A study to determine the prevalence of leptospira-induced abortions in the central Kentucky equine population during the 1990 foaling season and to determine the leptospira serovars responsible was conducted. From July 1, 1989 through June 30, 1990, 32 (4.4%) of 726 submissions (fetuses, stillborn foals, and/or placentas) were diagnosed as leptospirosis by the fluorescent antibody test and/or microscopic agglutination test. Attempts were made to isolate leptospires from the fetal tissues and/or the dam's urine in 31 of these cases. Leptospira interrogans serovar kennewicki was isolated from 11 (35.5%) and serovar grippotyphosa from 2 (6.5%) of the 31 cases. Of 12 cases that were culture negative with serologically positive fetal fluids, 8 had titers against serovar pomona, 1 against bratislava, 1 against grippotyphosa, 1 against hardjo, and 1 against both bratislava and pomona. PMID- 1515490 TI - Comparison of six commercially available transport media for maintenance of Serpulina (Treponema) hyodysenteriae. AB - Two anaerobic (A1 and A2), 1 selective (S1), and 3 conventional (C1, C2, and C3) transport media formulations were compared for their capacity to maintain the viability of Serpulina (Treponema) hyodysenteriae. Initial experiments compared the recovery of S. hyodysenteriae from pure cultures held in each transport medium for 0.5, 1, 2, 3, 5, and 7 days at -40 C, 4 C, 25 C, and 36 C. Subsequent experiments compared each transport medium for maintenance of S. hyodysenteriae in fecal specimens obtained from experimentally infected pigs after holding for up to 7 days at 25 C. In each experiment, the viability of S. hyodysenteriae in each transport medium incubated at each temperature and for each period was determined by inoculating the transport medium onto either trypticase soy agar with 5% sheep blood or selective BJ agar and incubating at 42 C anaerobically. Viability and fecal flora contamination were evaluated blindly after 2-, 4-, and 6-day incubation periods. At -40 C, recovery of viable S. hyodysenteriae from pure culture did not differ among the transport media from 0.5 to 7 days, and all of the transport media consistently maintained the viability of the spirochetes for 7 days. At 4 C, the anaerobic and selective transport media maintained the viability of pure cultures of S. hyodysenteriae significantly better than did the conventional transport media group at day 7 (P = 0.019). At the same temperature, the anaerobic media maintained viability better than did the conventional media at 5 days (P less than 0.042).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1515491 TI - Chronic gastroenterocolitis in nine cats. AB - Lesions of a chronic gastroenterocolitis were found in 9 cats of the Persian breed that were euthanized after a prolonged period of bloody diarrhea. Gross lesions consisted of gastrointestinal edema with prominent Payer's patches, multiple grayish nodules, and a few irregular erosions within the colonic mucosa. Microscopically, the changes were composed of degeneration, necrosis, and proliferation of gastric glandular epithelium, dilated intestinal crypts with lymphoplasmacytic cell infiltration of the lamina propria, and in 1 cat, severe transmural necrosis of the colon. With the Giemsa stain, spiral-shaped organisms in the gastrointestinal lumen and intracellularly in the gastric and the colonic epithelium were observed. These organisms could not be cultured. Although the role of these spiral-shaped organisms was not determined, other agents that could explain the disorder were not found. PMID- 1515492 TI - Canine leishmaniasis caused by Leishmania leishmania infantum in two Labrador retrievers. AB - Canine leishmaniasis, a generally fatal parasitic disease, was diagnosed in 2 dogs with a medical history of foreign travel, lymphadenopathy, emaciation, anorexia, intermittent fever, and cutaneous lesions. Clinically, hyperproteinemia, proteinuria, azotemia, and glomerulopathy were evident. Isolation of Leishmania species was done using Schneider's Drosophila medium. Syrian hamsters were used for infectivity studies. Clear taxonomic identification was done biochemically by isoenzyme analysis and comparison of zymogram banding patterns with 6 World Health Organization reference strains. Based on the geographic origin of affected dogs, clinicopathologic presentation, visceralization with hepatosplenomegaly in hamsters, and isoenzyme analysis, a diagnosis of Leishmania leishmania infantum was made. This study, representing the first taxonomic identification of an isolate from canine leishmaniasis, demonstrates the zoonotic and epidemiologic implications of this disease. PMID- 1515493 TI - Hairy vetch (Vicia villosa Roth) poisoning in cattle: update and experimental induction of disease. AB - Hairy vetch poisoning (vetch-associated disease) of cattle is a generalized disease characterized pathologically by infiltration of skin and many internal organs by monocytes, lymphocytes, plasma cells, and often eosinophils and multinucleated giant cells and clinically by dermatitis, pruritus, often diarrhea, wasting, and high mortality. The disease was experimentally reproduced in an adult Angus female that had recovered from the natural disease 1 year earlier. She developed dermatitis on the 11th day of vetch feeding, and despite withdrawal from the vetch diet on the 12th day, death occurred 24 days after first day of vetch feeding. The cow developed lymphocytosis and hyperproteinemia. The results of other hematologic evaluations, blood chemical profiles, urinalysis, and cutaneous hypersensitivity tests using vetch lectin were normal. Lymphocyte blastogenesis studies with vetch lectin were not interpretable. Necropsy revealed gross lesions characteristic of the disease in the skin, heart, kidney, adrenal, and lymphoid tissues. Microscopically there was typical cellular infiltration in those organs and in the thyroid, liver, pancreas, salivary and mammary glands, urinary bladder, corpus luteum, and cerebral meninges. Cutaneous apocrine gland necrosis was present. The inflammatory reaction has qualities of a type-IV hypersensitivity reaction. Hypersensitivity may occur when constituents of the ingested plant are absorbed and act as antigens that sensitize lymphocytes and evoke the multisystemic granulomatous inflammatory response that characterizes the disease. Alternatively, vetch lectin may directly activate T lymphocytes to initiate the cellular response. Vetch-like diseases have been associated with a variety of diets that did not contain hairy vetch.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1515494 TI - A rapid, sensitive thin layer chromatography procedure for the detection of fumonisin B1 and B2. AB - A thin layer chromatography (TLC) method was developed for the detection of fumonisin B1 and B2 in corn and corn-based feedstuffs. Finely ground samples were extracted with acetonitrile:water (1:1), filtered, and applied to C18 cleanup columns. The columns were washed with 1% aqueous KCl followed by acetonitrile: 1% aqueous KCl (1:9), and the fumonisins were eluted with acetonitrile:water (7:3). The eluants were concentrated and spotted on reverse-phase C18 TLC plates along with fumonisin B1 and B2 standards, and the plates were developed in methanol: 4% aqueous KCl (3:2). The fumonisins were visualized by spraying the TLC plates successively with 0.1 M sodium borate buffer, fluorescamine, and 0.01 M boric acid. The plates were then dried and examined under longwave ultraviolet light. Fumonisin B1 and B2 appeared as bright yellowish-green fluorescent bands at Rfs of 0.5 and 0.1, respectively. The detection limit for the fumonisins on the TLC plate was 0.1 ppm in corn. Recoveries from spiked samples averaged greater than 80%. The identification of the fumonisins was confirmed by hydrolyzing the parent compounds of B1 and B2 to their respective C22 amino-alcohols and reexamining by TLC with the same visualizing reagents. This procedure was used to survey 193 corn samples collected from University of Missouri test plots in 1990 for fumonisin B1. Fumonisin B1 was detected in 15% of the corn samples. PMID- 1515495 TI - Fumonisin toxicity in broiler chicks. AB - The effects of dietary fumonisin B1 were evaluated in young broiler chicks. The experimental design consisted of 5 treatments each with 9 randomly allotted male broiler chicks. Day-old chicks were fed diets containing 0 (feed control), 100, 200, 300, or 400 mg fumonisin B1/kg feed for 21 days. Response variables measured were chick performance, organ weights, serum biochemistry, and histologic parameters. Body weights and average daily gain dramatically decreased with increasing dietary fumonisin B1, and liver, proventriculus, and gizzard weights increased. Diarrhea, thymic cortical atrophy, multifocal hepatic necrosis, biliary hyperplasia, and rickets were present in chicks fed diets containing fumonisin B1. Serum calcium, cholesterol, and aspartate aminotransferase levels all increased at higher fumonisin dietary levels. Results indicate that fumonisin, from Fusarium moniliforme culture material, is toxic in young chicks. PMID- 1515497 TI - Surveillance for lesions of bovine spongiform encephalopathy in US cattle. PMID- 1515496 TI - Arsenic concentrations in tissues and body fluids of dogs on chronic low-level dietary sodium arsenite. AB - Twenty-four female Beagle dogs, 7-8 months old, were assigned to 4 groups. Control, low-dosage, medium-dosage, and high-dosage groups were offered 0, 1, 2, and 4 mg of sodium arsenite per kilogram of body weight per day (mg/kg/day), respectively, in their feed (equivalent to 0.0, 33.4, 66.7, and 133.4 micrograms/g in feed). On day 59, the dosage was doubled for the rest of the experiment, which ended on day 183. In general, arsenic concentrations in tissues and body fluids reflected arsenic levels in feed. Arsenic caused a dose-related decrease in food intake. Statistically significant differences in blood, liver, and kidney arsenic were detected, in most cases, between the 2 higher dosage groups and controls. The greatest differences in arsenic concentrations between groups were present in urine and hair. Results indicate that urine and hair would be the most useful specimens for chemical analysis when attempting to confirm low level dietary inorganic arsenic exposure or poisoning. PMID- 1515498 TI - Listeriosis in California broiler chickens. PMID- 1515499 TI - Campylobacter jejuni isolated from ratites. PMID- 1515500 TI - Use of oligodeoxynucleotide probes to verify Campylobacter jejuni as a cause of bovine abortion. PMID- 1515501 TI - Necropsy findings from Vietnamese potbellied pigs, 33 cases. PMID- 1515502 TI - Multifocal polioencephalomyelomalacia in Simmental calves with elevated tissue aluminum and decreased tissue copper and manganese. PMID- 1515503 TI - Systemic granulomatous disease in a horse grazing pasture containing vetch (Vicia sp.). PMID- 1515505 TI - Lead toxicosis in a group of cats. PMID- 1515504 TI - Systemic granulomatous disease in cattle in California associated with grazing hairy vetch (Vicia villosa). PMID- 1515507 TI - Neospora-like protozoal infections associated with abortion in goats. PMID- 1515506 TI - Japanese pieris toxicosis of goats. PMID- 1515508 TI - Two models for transforming auditory signals from head-centered to eye-centered coordinates. AB - Two models for transforming auditory signals from head-centered to eye-centered coordinates are presented. The vector subtraction model subtracts a rate-coded eye position signal from a topographically weighted auditory target position signal to produce a rate-code of target location with respect to the eye. The rate-code is converted into a place-code through a graded synaptic weighting scheme and inhibition. The dendrite model performs a mapping of head-centered auditory space onto the dendrites of eye-centered units. Individual dendrites serve as logical comparators of target location and eye position. Both models produce a topographic map of auditory space in eye-centered coordinates like that found in the primate superior colliculus. Either type can be converted into a model for transforming visual signals from retinal to head-centered coordinates. PMID- 1515509 TI - Quantitative measurement of two-component pH-sensitive colorimetric spectra using multilayer neural networks. AB - The purpose of this research was to develop a noise tolerant and faster processing approach for in vivo and in vitro spectrophotometric applications where distorted spectra are difficult to interpret quantitatively. A PC based multilayer neural network with a sigmoid activation function and a generalized delta learning rule was trained with a two component (protonated and unprotonated form) pH-dependent spectrum generated from microspectrophotometry of the vital dye neutral red (NR). The network makes use of the digitized absorption spectrum between 375 and 675 nm. The number of nodes in the input layer was determined by the required resolution. The number of output nodes determined the step size of the quantization value used to distinguish the input spectra (i.e. defined the number of distinct output steps). Mathematic analysis provided the conditions for which this network is guaranteed to converge. Simulation results showed that features of the input spectrum were successfully identified and stored in the weight matrix of the input and hidden layers. After convergent training with typical spectra, a calibration curve was constructed to interpret the output layer activity and therefore, predict interpolated pH values of unknown spectra. With its built-in redundant presentation, this approach needed no preprocessing procedures (baseline correction or intensive signal averaging) normally used in multicomponent analyses. The identification of unknown spectra with the activities of the output layer is a one step process using the convergent weight matrix. After learning from examples, real time applications can be accomplished without solving multiple linear equations as in the multiple linear regression method.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1515510 TI - Rate coherence and event coherence in the visual cortex: a neuronal model of object recognition. AB - We propose a function-oriented model of the visual cortex. The model addresses an essential task of the visual system: to detect and represent objects. These are defined as sets, which reappear in the input with invariant inner relations. A network, incorporating an idealized description of anatomical and physiological data, is presented with a movie showing various moving objects. In the course of time, as a result of Hebbian plasticity, a connection scheme develops which embodies in its forward and lateral connections the information necessary to perform the operations involved in object recognition. We demonstrate that coherent neural activity can exploit this information. Two types of coherence have to be distinguished in this respect. Rate coherence performs invariance operations and association, while event coherence accomplishes segmentation tasks. The model reproduces and explains experimental findings made both in physiological recordings from the visual cortex and in psychophysical studies. PMID- 1515512 TI - An analytical short- and long-term memory model of presynaptic plasticity. AB - A mathematical model, called the Learning Gate Model (LGM), that describes phenomena responsible for biological synaptic plasticity, is presented. The functionality of the model are mainly based on the work of Kandel and colleagues on the most elementary forms of learning observed in the Aplysia Californica marine mollusc. In particular, emphasis is placed on the double temporal dynamics of synaptic plasticity and the temporal specificity of classical conditioning. By properly modeling the effect of the binding of Ca++ ions to the serotonin sensitive adenylate cyclase enzyme, it is shown how a positively accelerated learning curve can be obtained for sensitization and classical conditioning. Phenomena of spontaneous recovery and second-order conditioning are reproduced through simulations. Mathematical analyses of the temporal trace of conditioned stimulus and of the Short-Term Memory steady state are also given. PMID- 1515511 TI - Three-dimensional head angular velocity detection from otolith afferent signals. AB - Afferent signals from the otolith organs can produce compensatory eye position and velocity signals which has been described as linear vestibulo-ocular reflex (LVOR). The afferent otolith signals carry information about head orientation and changes of head orientation relative to gravity. A head orientation (tilt) related position signal can be obtained from population vector coding of tonic otolith afferent signals during static or dynamic head tilts, which in turn could produce compensatory eye position signals in the LVOR. On the other hand, eye angular velocity signals may be extracted, as proposed in this study, from the population response of tilt-velocity sensitive otolith afferents. Such afferents are shown to encode instantaneous head orientation relative to gravity at onset of a head movement and, as the movement continues, the projection of head angular velocity onto the earth-horizontal plane, indicating the instantaneous direction of movement relative to gravity. Angular velocity components along the earth vertical direction which are not directly encoded by otolith afferents can be detected by central signal processing. Central reconstruction of 3D head angular velocity allows to obtain information about absolute head orientation in space even in the absence of semi-circular canal related information. Such information is important for generating compensatory eye movements as well as for dynamic control of posture. PMID- 1515513 TI - Motor control of voluntary arm movements. Kinematic and modelling study. AB - The motor control of pointing and reaching-to-grasp movements was investigated using two different approaches (kinematic and modelling) in order to establish whether the type of control varies according to modifications of arm kinematics. Kinematic analysis of arm movements was performed on subjects' hand trajectories directed to large and small stimuli located at two different distances. The subjects were required either to grasp and to point to each stimulus. The kinematics of the subsequent movement, during which subject's hand came back to the starting position, were also studied. For both movements, kinematic analysis was performed on hand linear trajectories as well as on joint angular trajectories of shoulder and elbow. The second approach consisted in the parametric identification of the black box (ARMAX) model of the controller driving the arm movement. Such controller is hypothesized to work for the correct execution of the motor act. The order of the controller ARMAX model was analyzed with respect to the different experimental conditions (distal task, stimulus size and distance). Results from kinematic analysis showed that target distance and size influenced kinematic parameters both of angular and linear displacements. Nevertheless, the structure of the motor program was found to remain constant with distance and distal task, while it varied with precision requirements due to stimulus size. The estimated model order of the controller confirmed the invariance of the control law with regard to movement amplitude, whereas it was sensitive to target size. PMID- 1515514 TI - Noninvasive diagnosis of coronary artery disease using a neural network algorithm. AB - This study examines the utility of neural networks for detecting coronary artery disease noninvasively by using the clinical examination variables and extracting useful information from the diastolic heart sounds associated with coronary occlusions. It has been widely reported that coronary stenoses produce sounds due to the turbulent blood flow in these vessels. These complex and highly attenuated signals taken from recordings made in both soundproof and noisy rooms were detected and analyzed to provide feature set based on the poles and power spectral density function (PSD) of the Autoregressive (AR) method after Adaptive Line Enhancement (ALE) method. In addition, some physical examination variables such as sex, age, body weight, smoking condition, diastolic pressure, systolic pressure and derivation from them were included in the feature vector. This feature vector was used as the input pattern to the neural network. The analysis was studied on one hundred recordings (63 abnormal, 37 normals). The network correctly identified 84% of the subjects with coronary artery disease and 89% of the normal subjects. PMID- 1515515 TI - Independent control of joint stiffness in the framework of the equilibrium-point hypothesis. AB - In the framework of the equilibrium-point hypothesis, virtual trajectories and joint stiffness patterns have been reconstructed during two motor tasks practiced against a constant bias torque. One task required a voluntary increase in joint stiffness while preserving the original joint position. The other task involved fast elbow flexions over 36 degrees. Joint stiffness gradually subsided after the termination of fast movements. In both tasks, the external torque could slowly and unexpectedly change. The subjects were required not to change their motor commands if the torque changed, i.e. "to do the same no matter what the motor did". In both tasks, changes in joint stiffness were accompanied by unchanged virtual trajectories that were also independent of the absolute value of the bias torque. By contrast, the intercept of the joint compliant characteristic with the angle axis, r(t)-function, has demonstrated a clear dependence upon both the level of coactivation and external load. We assume that a template virtual trajectory is generated at a certain level of the motor hierarchy and is later scaled taking into account some commonly changing dynamic factors of the movement execution, for example, external load. The scaling leads to the generation of commands to the segmental structures that can be expressed, according to the equilibrium-point hypothesis, as changes in the thresholds of the tonic stretch reflex for corresponding muscles. PMID- 1515516 TI - Diagnosis and treatment of early melanoma. NIH Consensus Development Conference. January 27-29, 1992. AB - The National Institutes of Health Consensus Development Conference on Diagnosis and Treatment of Early Melanoma brought together experts in dermatology, pathology, epidemiology, public education, surveillance techniques, and potential new technologies as well as other health care professionals and the public to address (1) the clinical and histological characteristics of early melanoma; (2) the appropriate diagnosis, management, and followup of patients with early melanoma; (3) the role of dysplastic nevi and their significance; and (4) the role of education and screening in preventing melanoma morbidity and mortality. Following 2 days of presentations by experts and discussion by the audience, a consensus panel weighted the scientific evidence and prepared their consensus statement. Among their findings, the panel recommended that (1) melanoma in situ is a distinct entity effectively treated surgically with 0.5 centimeter margins; (2) thin invasive melanoma, less than 1 millimeter thick has the potential for long-term survival in more than 90 percent of patients after surgical excision with a 1 centimeter margin; (3) elective lymph node dissections and extensive staging evaluations are not recommended in early melanoma; (4) patients with early melanoma are at low risk for relapse but may be at high risk for development of subsequent melanomas and should be followed closely; (5) some family members of patients with melanoma are at increased risk for melanoma and should be enrolled in surveillance programs; and (6) education and screening programs have the potential to decrease morbidity and mortality from melanoma. The full text of the consensus panel's statement follows. PMID- 1515517 TI - [The life experiences and the implication of caregivers in persons living with HIV]. AB - This article focuses on a qualitative study, conducted in Montreal between March and July of 1990, whose aim was to understand the life experiences and the needs of close and supportive individuals that care for seropositive persons. The objective of the study is to help provide more direction to the scope of services dispensed by the Centre Pierre-Henault, an organization created by a group of close supporters of HIV-infected persons. Eighteen individuals volunteered for the in-depth interviews: nine of these were caring for persons who had developed AIDS, four were providing support for persons who were HIV-positive, and the remaining five had assisted persons who passed away following AIDS-related diseases. The study shows that the risk of isolation is greater among those close supporters who provide care for HIV-positive persons. Although research does point to a number of fundamental traits that are shared among all types of supportive individuals, certain traits are specifically related to people caring for HIV-positive persons, including the taboo and the stigma that are linked to AIDS, as well as the rapid and unforeseen loss of people in their prime. PMID- 1515518 TI - [Psychosocial intervention for persons infected with HIV]. AB - We describe a psychosocial intervention program designed to enhance coping with the stress associated with HIV infection. The NUCARE intervention program is based on six components of coping including: cognitive reframing, problem solving, relaxation, goal setting, social support and use of resources and services. The rationale and development of the intervention is discussed and practical case examples illustrating the benefits of each component are presented. PMID- 1515519 TI - [Particulars of crisis intervention in seropositive persons or the existential crisis of HIV]. AB - This article presents a vision of crisis intervention for seropositive persons following an approach inspired by existential psychology. Persons who intervene must view crisis intervention for HIV-positive persons as an exploration of the close relation that exists between life and death. They must investigate the interrelations with the dimensions who intervene must view crisis intervention for HIV-positive persons as an exploration of the close relation that exists between life and death. They must investigate the interrelations with the dimensions of time, space, world and body. They must also examine the characteristics of the seropositive experience that are specific to the different infected clienteles. The welcoming process, the urgency of the situation and the therapeutic complementarity must be considered as the main guidelines for this type of crisis intervention which, in addition, must take into account the various life experiences that are particular to each of the HIV-positive persons. This approach requires that the person who intervenes and plays a supporting role must put into question their own attitudes toward the phenomenon at hand. Finally, life with the infection can also bring certain intervenors and clients to discover and profit from a number of unsuspected benefits. PMID- 1515520 TI - [The effects of perinatal infection with the HIV virus on the development of adaptive behavior]. AB - This study examined the development of adaptive functioning in nine HIV-positive and nine HIV-negative children ranging in age from 3 months to 6 years, 11 months. Both groups showed normal development of adaptive behaviour prior to two years of age; after this time the HIV-positive group was impaired in all areas of functioning. The results are discussed in terms of the program needs of the HIV infected children and their families. PMID- 1515521 TI - [Psychosocial factors influencing the intention of women infected with HIV to have a child: study of 12 cases]. AB - This study documents the factors that influenced the decision of 12 women of child-bearing age whether to have a child in the three years following an infection by the human immunodeficiency virus (HIV). Three of the 12 women are intending to have a child, and their intention stems from their beliefs and positive attitudes toward having a child, their partner's positive influence, the absence of their children, their denial of the disease and the absence of symptoms within their family. For the nine other women, the factors that influenced their decision not to have a child include the sociopolitical and economical context, the fact their family is complete, the fact they are seropositive or III, their fear of transmitting the infection and the idea of losing a child to AIDS. PMID- 1515522 TI - [Psychotherapy in child incest: the dangers of a psychic break]. AB - There seems to be a consensus today by which a child, who is a victim of incest or sexually abused, must be directed to therapy in order that he or she provides a factual account of the traumatism and, by the same token, exorcises it. The authors deplore the widespread use of this destabilizing method. They emphasize that, for many children, recovery is achieved more successfully through "repression" (in the psychoanalytical sense of the term). After having obtained disclosure from the child, the authors argue that it is preferable for the intervenor to create the appropriate therapeutic conditions allowing the child to positively bury the event and move on with his or her life. PMID- 1515523 TI - [The sexual needs of homosexual HIV seropositive men]. AB - A two-step study was conducted to identify the sexual needs of a group of seropositive homosexual men. At first, there was an interview with 30 men which aimed to define their objectives of sexual health. This was followed by a questionnaire distributed among 88 seropositive men and 173 seronegative men, who evaluated the objectives stated in the first step. The statistical analysis of collected data allowed for the identification and narrowing down of four major needs: being in good health, being in love, being sexual and, to a lesser degree, being secure. Results are discussed and point to the role played by the biological, psychological and sociological uneasiness in the context of the difficulties that seropositive homosexual men have in satisfying their sexual needs. This evaluation can prove useful in the planning and the implementation of sexological services for HIV-positive persons. PMID- 1515524 TI - [Quality of relations between gay couples and high-risk sexual behavior]. AB - This study examines the hypotheses by which quality relationships among gay couples is closely related to the adoption of low-risk sexual behaviours, in monogamous and non-monogamous situations. Data was collected from 29 homosexual couples (58 men) of the Montreal area. The survey, which graded sexual conduct as well as adjustments made within the relationship, confirmed the author's hypothesis. Indeed, the distribution of couples according to a multifactorial risk index does in fact establish a connection between the couple's happiness and the level of risk during sexual relations within and outside the couple. These conclusions are discussed in light of existing data pertaining to the link between health and the quality of a relationship among heterosexual couples. PMID- 1515525 TI - [Psychiatric repercussions of HIV infection. Current update]. AB - Persons infected by the HIV virus are known to be vulnerable to psychological and neuropsychiatric complications. The state of knowledge today indicated that the organic cerebral syndromes and adaptation problems are among the most frequent complications requiring a psychiatric intervention. Affective problems represent yet another possible type of complication. The author provides an update of current knowledge on the nature of these problems, as well as their treatment. PMID- 1515526 TI - [Spiritual support in HIV seropositivity or AIDS]. AB - Acute life experiences ("experiences limites de l'existence") have long been considered the exclusive domain of religion. Until recently in Quebec, the Catholic Church was noted for overseeing these symbolic events. Although the religious reference has not completely disappeared, the author argues that it has now undergone two changes, in terms of privatization and diversification. As such, several systems of belief, whether religious or secular, are being suggested to provide meaning to our lives. Yet, can these approaches provide any relevant support to patients in general, and to HIV-infected persons in particular, including the various organizations and individuals that provide care and assistance? The author points out that genuine support for seropositive persons or AIDS patients in their search for meaning and their fight against the negative forces in life, must involve a person's spiritual dimension. The outcome of this indispensable process does not necessarily have to lead to a traditional religious creed. However, in considering the issue of spiritual support in the context of illness and suffering, the author concludes that "belief in the search for meaning" is an imperative for all those who are concerned by AIDS. PMID- 1515527 TI - [AIDS and adolescence]. PMID- 1515528 TI - [Validation of a life experiences inventory in adolescents]. PMID- 1515529 TI - [Clinical reflections on the setting up of a residence for social reinsertion of schizophrenics]. PMID- 1515530 TI - [The evolution of child custody after the separation of the parents]. AB - Following the separation of spouses, a family undergoes a reorganization process where the choice of a formula for child custody represents a major step, which child's living environment will depend on. Despite the importance of this form of custody, it seems, in the context of the crisis following separation, that decisions surrounding that choice are often taken haphazardly, without much consideration of various alternatives. On a different note, the family's profile at the time of the separation is bound to change following the pace of the child's and the parent's development. What may seem a relevant formula for a three year-old child may not necessarily be the case when the child turns eight. This article looks at the extent to which the child custody formula evolves to adjust itself to the changing needs of children and parents. Research focused on a sampling of 112 families separated for an average of four and a quarter years, with children aged 10 (N = 49) or adolescents of 15 years of age (N = 63). Data was compiled through a telephone questionnaire filled out by the parent who was the most committed to the child's custody. The description of the two categories of change (minor and major) was made according to the original child custody formula, the time lapse since the separation, the child's age and parental re composition. Results point to three main trends: a) child custody arrangements do not evolve much over time; b) when there are changes, these are especially motivated by the needs of the parents; and c) the changes mainly result in reducing the frequency of contacts between the child and the parent without custody. PMID- 1515531 TI - [Social work and mental health: a critical outline]. PMID- 1515532 TI - [The access project: a continuing experience in Montreal]. PMID- 1515533 TI - [Aurore, child martyr. Essay on violence done to children]. AB - This article draws on the sad story of Aurore Gagnon, a battered child raised in rural Quebec and whose turmoil was dramatized on film. By elaborating on this symbol, the author is able to generate, at least in a systemic perspective, a number of issues and outlooks that go far beyond the generalities usually associated with this tale. For instance, there is ample evidence showing that the behaviour of Aurore's stepmother, aberrant as it may be, is largely caused by a set of environmental circumstances. Of course, today's social conditions hardly resemble those of the past. Yet, given the conjunctions of certain factors, children, who are nevertheless our most valuable asset, continue to be in danger in the presence of their very own parents. PMID- 1515534 TI - [Psychological distress in persons afflicted with HIV in Montreal]. AB - This paper describes the HIV-related mental health concerns of a sample of 128 persons with HIV infection in Montreal who participated in a larger national survey of HIV-related mental health needs and services in Canada. We examined mental health distress in persons with HIV infection in Montreal compared to other cities in Canada, and in subgroups of HIV-infected Montrealers defined on the basis of sex, age, diagnosis, and risk factor status. Results demonstrate that although HIV infection has a strong and far reaching impact on mental health, there are differences in the types of concerns and issues that are distressing to specific groups of Montreal respondents. Uncertainty about the future and not being able to realize life goals, as well as feelings of helplessness and fears about potential adverse neurological consequences of HIV disease, were major sources of psychological distress. Feelings of depression, anxiety, and anger, as well as concerns about increasing physical disability, pain, infecting others, confidentiality, and finances were predominant concerns among specific subgroups. Differences between respondents in terms of source of income, age, and sex, and to a lesser extent diagnosis and risk factor status, were associated with varying levels of mental health distress. Although respondents in Montreal (and Vancouver) were more distressed than respondents in Toronto and Halifax, these differences appear to be due primarily to differences in age and source of income. Findings from this study will be useful to policy makers and health planners in developing services to meet the mental health needs of HIV infected adults. PMID- 1515535 TI - [Promotion of mental health in seropositive persons and persons with AIDS]. PMID- 1515536 TI - [AIDS and mental health]. PMID- 1515537 TI - [Consequences of AIDS in the lives of hemophiliacs and their caregiving families in Quebec: stress, response to stress and social support]. AB - The following article focuses on the Quebec portion of a national survey on the care needed by hemophiliacs with AIDS or having contracted the HIV virus. The survey was based on an approach that considers social support as a means to face stress. It also examined the needs of dispensers of care and relatives (whether mourning or not) of these persons. Participants revealed having experienced more stress because of an absence of support or simply negative support, than because of the physical deterioration caused by the disease. In addition, the question of confidentiality was often raised. In general, participants said they were satisfied with the support they had received, especially on the part of members of their family. PMID- 1515538 TI - Critical analysis of objections against the biological molecular energy machines. AB - In the past, two important objections against McClare's idea of biological molecular energy machines were raised. One of the criticisms was concerned with the origin of energy gained in ATP cleavage and with an interpretation of McClare's "excited vibrational state." The former argument reveals a failure of the critics to comprehend McClare's approach. As to the excited vibrational state, it can be identified with nonequilibrium conformational states of the unit rather than with a single vibrational mode. The other criticism based on Brillouin's energy cost of measurement argued that reversible operation of biological molecular energy machines would be virtually impossible. Using propagation velocities of deformations of the unit's structure (instead of velocity of light), the objections against reversibility are invalidated even in the framework of the critic's approach. McClare's idea and relevant definitions are thus physically correct. PMID- 1515539 TI - Plausible view on the biological molecular energy machines. AB - A qualitative picture of operation modes of biological molecular energy machines is presented. It is suggested that there is mutual control between the flow of molecular energy stored in a biological molecular energy machine and the sequence of nonequilibrium conformational states through which the machine passes in doing work. If the structure of the conformational space is favorable, the set of trajectories in this space decomposes into two families, each of which accomplishes another task. This divergence of trajectories enables to distinguish molecular objects according to differences in interaction between the machine and the object, i.e., to perform a measurement on a molecular object and process the object according to the result of that measurement. PMID- 1515540 TI - Hydrophobic interaction between globin helices. AB - The interhelical interfaces have been examined in seven high-resolution globin chains. The profiles of hydrophobic contact, as measured by the residue solvent accessible area loss upon folding, have been calculated. The seven globins studied differ in their overall loss of solvent-accessible area upon packing of their helices, the order being 1MBD greater than 1LH1 greater than 1ECD greater than 2MHBB greater than 2HHBB greater than 2HHBA greater than 2MHBA, which gives a measure of the difference in stability due to the hydrophobic interaction. The five helix-pair packings (AH, BE, BG, FH and GH) examined in detail have qualitative similarities. There are, however, substantial quantitative differences both at the equivalent residue level and at the level of overall helix-helix contact, which has significance in some models of folding. The AH pair has the most uniform area loss over the seven globins and the largest variation in accessible area loss on packing among the five helix pairs is the GH pair. The set of residues required to produce the globin fold has been deduced from the residue area losses. PMID- 1515541 TI - Helix formation in methylated copolymers of lysine and alanine. AB - Random copolymers of lysine and alanine, 2:1 and 1:1, were trimethylated on the lysine amino groups to quaternary ammonium groups. Methylated and unmethylated polymers were prepared with Cl- or ClO4- as the counterion. CD spectra were measured for increasing concentration of peptide without added salt, and at constant peptide concentration in increasing NaCl or NaClO4. Unmethylated peptides, as the chloride, form alpha-helix more readily than do the methylated peptides. The opposite occurs with ClO4- as counterion. The helix-promoting effect of methylated lysine residues (ClO4- counterion) is diminished by the presence of alanine, as compared with effects when lysine is the only type of residue. The effect of methylation of proteins on helix formation may depend on the types of anionic groups with which the protein may be involved. PMID- 1515542 TI - Early assembly pathways of type I collagen. AB - A method was developed for computing the free energy (delta Fi) of aggregates of type I collagen. The method was based on a treatment of Matheson and Flory describing phase equilibria of rigid rod polymers. It included a polymer-solvent interaction term that depended on near neighbor transfer energies. Extrahelical portions of the molecule were assigned local interaction energies differing from that assigned to the helix. Free energies of reaction for successive steps along assembly pathways (delta Fi-i+1) were computed. When allowance was made for specific pairing between extrahelical and helical domains, the so-called D staggered (D = 670 A) alignment of molecules was preferred, as opposed to a nonstaggered, or nematic, alignment. Based on delta Fi-i+1 alone, it appeared that 1D-staggered oligomers arise first in assembly, followed later by addition of molecules in 4D alignment. Neither 4D dimers nor 4D-8D trimers were predicted to be major intermediates in assembly. This result is contrary to previous hypotheses. When energies of activation were included in the analysis, the prediction was less certain, and specific circumstances were identified in which 4D dimers and 4D-8D trimers were the earliest aggregated species in assembly. PMID- 1515543 TI - Langevin dynamics of peptides: the frictional dependence of isomerization rates of N-acetylalanyl-N'-methylamide. AB - The rate constant for the transition between the equatorial and axial conformations of N-acetylalanyl-N'-methylamide has been determined from Langevin dynamics (LD) simulations with no explicit solvent. The isomerization rate is maximum at collision frequency gamma = 2 ps-1, shows diffusive character for gamma greater than or equal to 10 ps-1, but does not approach zero even at gamma = 0.01 ps-1. This behavior differs from that found for a one-dimensional bistable potential and indicates that both collisional energy transfer with solvent and vibrational energy transfer between internal modes are important in the dynamics of barrier crossing for this system. It is suggested that conformational searches of peptides be carried out using LD with a collision frequency that maximizes the isomerization rate (i.e., gamma approximately 2 ps-1). This method is expected to be more efficient than either molecular dynamics in vacuo (which corresponds to LD with gamma = 0) or molecular dynamics in solvent (where dynamics is largely diffusive). PMID- 1515544 TI - Partial molar volumes of the amino acid side-chains of proteins in aqueous solution: some comments on their estimation using partial molar volumes of amino acids and small peptides. AB - The partial molar volumes of some amino acid side-chains were determined in two recent studies [Makhatadze, G.I., et al. (1990) Biopolymers 30, 1001, and Reading, J.F. & Hedwig, G.R. (1990) J. Chem. Soc. Faraday Trans. 86, 3117] using partial molar volume data, V02, in aqueous solution at 25 degrees C for some peptides of sequence Gly-X-Gly, where X is an amino acid. These side-chain partial molar volumes are critically compared with those obtained using V02 data for amino acids. It is concluded that side-chain partial molar volumes calculated using V02 data for the tripeptides are better estimates of side-chain partial molar volumes in proteins than are those determined using V02 data for amino acids. PMID- 1515545 TI - Theory of delocalized ionic binding to polynucleotides: structural and excluded volume effects. AB - A previously developed theory for the delocalized binding of ions to polyelectrolytes was restricted to point ions and a structurally rigid polyelectrolyte. For the binding of substances like oligolysines and polyamines to DNA, the restriction to point ions would appear not to be realistic. For the binding of ions to flexible chains like single-stranded polynucleotides, the restriction to a rigid polyelectrolyte may not be realistic. In this article, we assess the effect of relaxation of these two restrictions. Excluded volume among bound ions is modeled by a hard-rod potential in the context of the theory of a one-dimensional fluid. The possibility that a flexible chain folds in some manner in the immediate vicinity of a bound ion is modeled by allowing the mean spacing between charged groups on the polymer to become smaller as the number of bound ions increases. We compare our results with recent data on the binding of a series of oligolysines to single-stranded polynucleotides, which conflict with the predictions of the original theory of delocalized binding of point ions to rigid polyelectrolytes. Inclusion of excluded volume among bound ions does not significantly improve agreement with the data. Substantial improvement in the level of agreement is obtained when the polyion chain is assumed to be flexible. One of our conclusions is that the excluded-site description of anticooperativity, which was designed for the binding of ligands to discrete sites on a polymer chain, and which does not include the effect of ionic forces, should not be used in cases of delocalized binding of ions. PMID- 1515546 TI - Computer modeling of polysaccharide-polysaccharide interactions: an approach to the kappa-carrageenan-mannan case. AB - A computer program SAINT has been developed for the investigation of the structure and for the prediction of minimum-energy structure of polysaccharide polysaccharide complexes. The energy minimization is carried out on internal geometrical parameters--namely bond angles, torsional angles, and five parameters describing the mutual orientations of polysaccharide chains. For this purpose, the nonderivative method of conjugated directions is used. This procedure was applied to computer modeling of an idealized model of the binary gelling kappa carrageenan and galactomannan system. It is shown that the interaction between two chains influences the structure of the individual polysaccharide molecule and that in the minimum-energy structures of the complex, the conformation of the chains does not correspond to the lowest energy. PMID- 1515547 TI - Theoretical determination of conformational paths in citrate synthase. AB - Two methods are developed for the theoretical determination of a conformational path between two well-documented forms, a closed form and the open form [Remington et al. (1982) J. Mol. Biol. 158, 111-152] of pig heart citrate synthase, a dimeric enzyme of 2 x 437 residues. The first method uses the minimization of the sum of the potential energies at a set of equidistant points, according to Elber and Karplus [(1987) Chem. Phys. Lett. 139, 375-380]. The initialization of the algorithm is modified to account for large-angle rotations of many groups by performing the interpolations in the space of internal polar coordinates of a set of generalized Jacobi vectors earlier introduced by Durup [(1991) J. Phys. Chem. 95, 1817-1829] and by carefully testing all choices of directions of rotation for determining the initialized midpoint between the known forms. The path includes intermediate points, created by successive splittings of each interval into two equal parts, with a partial energy minimization performed after each splitting. The minimization encounters the well-known local-minima problem, which here is handled by low-temperature molecular dynamics annealing. It is shown that the best ratio of potential energy decrease to rms deviation is achieved by running the dynamics at 50 K, as compared to 100 K and above. The main character of the path obtained is the occurrence of strong to-and-fro variations of some dihedral angles at specific stages along the path. The second method, which we name directed dynamics, uses only low-temperature molecular dynamics simulations by starting trajectories from each of the two known forms with initial velocities directed toward the other one. The procedure is iterated by restarting trajectory pairs after the points of closest approach of the preceding pair. The two half-paths thus built eventually meet after 70 iterations. This method provides a second path with strong similarities, as well as some differences, with respect to the path obtained by the first method. PMID- 1515548 TI - Cytokines and proteases in invasive processes: molecular similarities between inflammation and cancer. AB - Tumor-derived serine proteinases and metalloproteinases have been associated with invasion and metastasis of cancer cells. Leukocytes, particularly monocytes/macrophages and neutrophils, actively synthesize and store these proteolytic enzymes. The production by tumor cells of chemotactic factors that attract white blood cells raises questions that are important for the basic researcher as well as the clinical scientist. Are the proteinases, which have the capacity to dissolve the extracellular matrix and by this solubilization promote cell migration, the same in tumor cells as in normal cells? Is the production of chemotactic factors by tumor cells a coincident epiphenomenon of the malignant state or a selective way to parasitize the host? Does the early attraction of leukocytes to the tumor site contribute to early host defense against cancer? Does our knowledge about mechanisms of action of cytokines have implications for therapy of the cancer patient? Recent experimental data give hints to the answers to these questions and make it possible to deduce a fundamental model of cytokine mediated proteolysis in tissue remodelling. PMID- 1515549 TI - Interferon-gamma, more of a cachectin than tumor necrosis factor. PMID- 1515550 TI - Molecular area involved in the in-vitro dimerization of the murine p55 IL-2 receptor. AB - In order to study structure-function relationships of the M(r) 55,000 subunit of the murine IL-2R (p55 IL-2R) by epitope mapping, we have expressed the p55 IL-2R molecule in a cell-free translation system. Under these in vitro conditions, we detected the expected p55 IL-2R polypeptide initiated at Met 1 and, in addition, two internally initiated molecules at Met 64 and Met 105. In this report we describe that from such a mixture, containing three molecular species of p55 IL 2R, mAb 135D5 immunoprecipitated the polypeptide initiated at Met 105 although this N-terminally truncated form of p55 IL-2R does not contain its epitope located between amino acids 72-88. This observation can be taken as a further evidence for the formation of p55 IL-2R dimers. Finally, we identified the region implicated in the formation of p55 IL-2R dimers close to the transmembrane region of the molecule. PMID- 1515551 TI - Butylated hydroxyanisole specifically inhibits tumor necrosis factor-induced cytotoxicity and growth enhancement. AB - The effect of commonly used food antioxidants on recombinant tumor necrosis factor alpha (rTNF-alpha)-induced cytotoxicity, growth enhancement and adhesion has been evaluated. Butylated hydroxyanisole (BHA) and 4-hydroxymethyl-2,6-di-t butylphenol (HBP) were the only two of nine antioxidants that completely inhibited rTNF-alpha-induced cytotoxicity in L929 and WEHI 164 fibrosarcoma cells. Ethoxyquin, propyl gallate and butylated hydroquinone only partially inhibited rTNF-alpha-induced cytotoxicity, while the antioxidants butylated hydroxytoluene (BHT), alpha-tocopherol, ascorbic acid and thiodipropionic acid had minimal effects. The only difference between the molecular structure of the efficient HBP and the non-efficient BHT, is a hydroxymethyl group instead of a hydroxyl group on the phenolic ring. Neither BHA nor BHT inhibited the activation of NF kappa B after 10 or 60 min challenge with rTNF-alpha in L929 cells. BHA also inhibited rTNF-alpha-induced, but not rIL-1 beta-induced growth enhancement in FS-4 fibroblasts. Further, BHA blocked both rTNF-alpha-induced and rIL-1 beta induced prostaglandin E2 synthesis in FS-4 fibroblasts. BHA inhibited the rTNF alpha-induced release of arachidonic acid in both FS-4 and L929 cells, suggesting that BHA inhibits cellular phospholipase(s). Neither alpha-tocopherol nor BHA inhibited rTNF-alpha-induced adhesiveness of human endothelial cells. The results indicate that BHA is a specific and potent inhibitor of rTNF-alpha- and rTNF-beta induced cytotoxicity, as well as of rTNF-alpha-induced growth enhancement. PMID- 1515552 TI - Biological effects of recombinant vaccinia virus-expressed interleukin 4. AB - Recombinant vaccinia viruses expressing murine interleukin 4 (IL-4), either alone or together with interleukin 2 (IL-2) or gamma interferon (gamma-IFN), were constructed. Unlike IL-2, IL-4 expressing viruses were not cleared from immunodeficient mice and the mice died. As they died more rapidly than immunodeficient mice inoculated with a control virus, it appeared that IL-4 contributed to their death and the IL-4 mediated toxicity was confirmed in normal immunocompetent mice. The toxicity was reversed by co-expression of either IL-2 or gamma-IFN, probably due to virus clearance and therefore lower levels of circulating IL-4. Vaccinia virus-expressed IL-4 did not increase antibody or natural killer cell levels and caused a slight decrease in cytotoxic T lymphocyte levels. PMID- 1515553 TI - Synergism of glucocorticoids with granulocyte macrophage colony stimulating factor (GM-CSF) but not interferon gamma (IFN-gamma) or interleukin-4 (IL-4) on induction of HLA class II expression on human monocytes. AB - Peripheral blood monocytes from up to 13 normal donors were stimulated with the cytokines interferon gamma (IFN-gamma), interleukin 4 (IL-4) and granulocyte macrophage-colony stimulating factor (GM-CSF) in the presence or absence of dexamethasone (Dex), and the effects on HLA class II (HLA-DR, DP and DQ) expression studied. Dex markedly augmented HLA-DR, DP and DQ levels induced by GM CSF, in all samples tested. Particularly striking were the effects on HLA-DQ expression, since stimulation with a combination of Dex and GM-CSF induced markedly higher levels of HLA-DQ antigen than stimulation with IFN-gamma. Northern blot analysis of samples treated for 40 hours with Dex and GM-CSF indicated that levels of DR alpha, DP alpha and DQ alpha mRNA were also increased. In contrast, despite variation between individual donors, in general Dex weakly inhibited both constitutive and IFN-gamma- or IL-4-induced HLA-DR expression. Variability in the responsiveness of monocytes purified from individual donors to each cytokine was also observed. GM-CSF was less potent than IFN-gamma and IL-4, enhancing HLA class II expression in only seven of 13 donors tested, whereas in the presence of Dex all donors responded to GM-CSF. The differential effects of glucocorticoids in vitro suggest that these cytokines induce HLA class II expression by different mechanisms. PMID- 1515554 TI - Circulating interleukin 6 as a useful marker for predicting postoperative complications. AB - We examined postoperative serial changes in the levels of serum interleukin 6 (IL 6), serum acute phase reactants (APRs) and plasma neutrophil elastase (NE) in patients with various cancers and reviewed these changes in patients who did, and did not, show postoperative complications. Serum IL-6 level was elevated after surgery, peaking on the first postoperative day. Elevation of serum APRs and plasma NE levels also followed. There was a significant correlation between the serum peak level of IL-6 and those of APRs and NE (P less than 0.01). Moreover, there was a significant difference in the serum IL-6 level in patients with and without complications. The relationship between the serum IL-6 greater than 400 pg/ml and the incidence of postoperative complications was also marked. These results suggest that circulating IL-6 is a clinically useful marker for the earliest detection and prediction of postoperative complications. PMID- 1515555 TI - Production and induction of a novel cytotoxin (factor 2) by a human B-cell line. AB - The human B-cell line, Karpas 160, was found to produce Factor 1 and 2 (F1 and F2). F1 was found to be indistinguishable from tumor necrosis factor beta (TNF beta), while F2 appears to be a new cytotoxin. We used several stimuli alone or in combination to trigger the 160b cells, a subclone of Karpas 160, to produce higher yield of F2. The optimal culture times, concentrations of cells and a range of stimuli were studied. We found that 20-25 ng/ml of phorbol myristate acetate (PMA) effectively induced the higher production of F2. Pretreatment of the cells with sodium butyrate enhanced F2 production. Production of TNF but not F2 was inhibited when the cells were cultured with tunicamycin and PDB. When ciprofloxacin or cycloheximide was added to the medium, F2 production in the presence of PMA was amplified. When 160b cells were cocultured with K562 cells, low levels of F2 induction were observed. We found that most types of human tumor cell lines were highly susceptible to F2, but less sensitive or even resistant to TNF. In contrast, normal human cell lines were not susceptible to F2. Therefore, it appears that F2 could be a new human cytotoxin. PMID- 1515556 TI - Gastric carcinoma in young Hong Kong Chinese. AB - Gastric carcinomas usually occur in older people. Those occurring in the young are uncommon. The pathological and clinical features of gastric carcinomas were reviewed in 42 Chinese patients who were 35 years of age and younger. The data were obtained from the record files of the University Department of Pathology, Queen Mary Hospital for the period 1976-85. The patients comprised 4% of the total cases of gastric carcinomas in that period. These patients (age range: 20 35 years, mean: 30 years) showed a male to female ratio of 1:2.5 which differs from the usual male preponderance seen in gastric carcinoma. Among the 27 cases with known staging, 22 (81.5%) were stage III or IV. Twenty-five cases had an ulcerative appearance. All were adenocarcinomas and the majority (83.3%) were poorly differentiated. Associated dysplasia was found in 35 (83.3%) cases, although only 14 of these were in association with poorly differentiated adenocarcinomas. Intestinal metaplasia was found in 13 cases and, when present, involved less than 30% of the mucosa. Only two cases were of type III metaplasia. The findings show that gastric carcinoma in young Chinese tended to occur more frequently in females, presented at late stages, showed poor glandular differentiation, was frequently associated with gastric dysplasia and had minimal association with intestinal metaplasia. PMID- 1515557 TI - Brush border hydrolases in normal and neoplastic colonic epithelium. AB - Previous studies have suggested that abnormal expression of enzymes characteristic of the intestinal brush border might accompany colonic neoplasia and possibly facilitate identification of epithelium at risk of malignancy. To test this possibility, the distribution of the brush border enzymes sucrase isomaltase (SIM), maltase-glucoamylase (MGA), aminopeptidase-N (APN) and diamino peptidylpeptidase-IV (DPPIV) were studied by the immunoperoxidase method in biopsies from the rectum and caecum of normal subjects, and neoplastic and non neoplastic tissues from patients with adenoma or cancer. Brush border enzymes were detected by immunohistochemistry more frequently in the caecum than the rectum (P less than 0.05) of normal subjects. Diamino-peptidylpeptidase-IV and APN were present in highest concentration at the brush border of the most mature colonocytes on the luminal surface with less staining in the crypt, whereas SIM and MGA staining of the brush border was as prominent on crypt cells as surface cells. While all cancers expressed at least one enzyme, there was heterogeneity of staining within tumours and a tendency to lose polarity of enzyme expression in cells, sometimes with dense staining of the cytoplasm. Distally situated adenomas uncommonly expressed a brush border enzyme (25%) and the only enzyme expressed in them was SIM. These finding indicate that these brush border enzymes are not exclusively expressed in the small intestine; DPPIV and APN are markers of the normal mature colonocyte and should prove useful as markers of differentiation. However, the change associated with neoplasia would not appear to be of clinically predictive value.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1515558 TI - Fluoride as a possible aetiological factor in non-ulcer dyspepsia. AB - A prospective case controlled study was conducted to evaluate the role of fluoride as a possible aetiological factor for non-ulcer dyspepsia (NUD). Twenty patients with NUD and 10 age and sex matched healthy controls were subjected to clinical evaluation, upper gastrointestinal endoscopy and biopsies from the gastric antrum and duodenum. The antral and duodenal mucosa was subjected to a rapid urease test for Helicobacter pylori and histological and electron microscopic examinations. Fluoride levels in the drinking water, serum and urine were estimated using a ION 85 ion-analyser. These levels were significantly higher in patients with NUD than in controls (P less than 0.05). Histological abnormalities in the antral and duodenal mucosa were seen in 14 patients (70%) with NUD and 1 control subject (10%) (P less than 0.05). Electron microscopic abnormalities in the mucosal cells were seen in all patients with NUD but in none of the controls (P less than 0.01). The fluoride levels in serum and urine correlated with the symptoms, histological and electron microscopic abnormalities (P less than 0.05). It was concluded that chronic exposure to fluoride may result in NUD and should be considered in patients where other known cause of dyspepsia have been excluded. PMID- 1515559 TI - C-reactive protein and lactate dehydrogenase isoenzymes in the assessment of the prognosis of acute pancreatitis. AB - The value of serum C-reactive protein, lactate dehydrogenase isoenzymes and erythrocyte sedimentation rate in predicting the outcome of acute pancreatitis was evaluated for 57 episodes in 54 patients. Serum C-reactive protein levels on day 2, 4 and 7 after admission were significantly higher in 19 episodes of severe attacks than in 38 episodes of mild attacks (13.71 +/- 9.68, 9.00 +/- 7.54, 6.02 +/- 3.83 vs 4.78 +/- 3.91, 3.30 +/- 3.61, 1.43 +/- 2.08 mg/dL; P less than 0.0001, P less than 0.005, P less than 0.0001, respectively). The sensitivity, specificity and accuracy of predicting a severe attack were 94, 76 and 82% using C-reactive protein greater than or equal to 8 mg/dL on day 2; 67, 92 and 84% using C-reactive protein greater than or equal to 5 mg/dL on day 7; and 59, 76 and 70% using Ranson's criteria greater than or equal to 3. Increases in LDH-4 and LDH-5 isoenzymes were found in both groups, with LDH-4 being slightly higher in severe attacks than in mild attacks. There was no significant difference of erythrocyte sedimentation rate between both groups. When compared with Ranson's criteria, lactate dehydrogenase isoenzymes and erythrocyte sedimentation rate, C reactive protein is more valuable in the early assessment of the severity of acute pancreatitis. PMID- 1515560 TI - Persistent ileitis after ileal salvage from a failed Kock pouch. AB - A case of persistent ileitis following the refashioning of a Kock ileal pouch into a Brooke ileostomy for severe pouchitis is reported. Preserving the terminal ileum by a salvage procedure may not be a safe alternative to pouch excision with the formation of a new end ileostomy in the surgical management of pouchitis refractory to medical treatment. PMID- 1515561 TI - Fulminant hepatic failure and acute intravascular haemolysis as presenting manifestations of Wilson's disease in young children. AB - The cases of three young children (mean age 5.8 years) in whom fulminant hepatic failure and acute intravascular haemolysis were the presenting manifestations of Wilson's disease are reported. Although diagnosis was made ante-mortem and chelation therapy instituted, the course was relentlessly fatal in all three cases. This presentation of Wilson's disease at such a young age is noteworthy. PMID- 1515562 TI - Safety and feasibility of percutaneous ultrasound guided puncture of the gall bladder for crystal analysis. AB - The safety and feasibility of ultrasound guided percutaneous aspiration (USPA) of bile, for bile crystal analysis was assessed critically. Forty-four patients about to undergo elective cholecystectomy underwent intended transhepatic USPA 1 h before their operation. At laparotomy a careful inspection for bile and blood leakage was made and a further sample of gall-bladder bile collected. Successful USPA occurred in 40 of the 44 patients. The four unsuccessful cases each had a gall-bladder packed with stones and contained virtually no bile. Three patients developed bile leak after transperitoneal (n = 2) and transhepatic (n = 1) puncture of the gall-bladder and another patient lost 100 mL of blood. Microscopic analysis of paired bile samples confirmed that gall-bladder bile (as opposed to hepatic bile) had always been aspirated. Ultrasound guided percutaneous aspiration of bile offers a simple and promising alternative to duodenal intubation, but considerable experience is required before it can be recommended as its replacement. PMID- 1515563 TI - Duplex-Doppler assessment of cirrhosis in patients with chronic compensated liver disease. AB - Portal venous flow velocity (PFV) was measured with duplex-Doppler equipment in 50 normal subjects and in 117 patients with suspected chronic liver disease who showed no evidence of decompensation such as ascites, hepatic encephalopathy, jaundice or oesophageal bleeding. All the patients underwent percutaneous liver biopsy which demonstrated non-cirrhotic liver disease in 58 cases (CH-patients: steatosis 8, persistent chronic hepatitis 8, active chronic hepatitis 42) and liver cirrhosis in the other 59 cases (LC-patients). The normal subjects and the CH-patients had similar values of max-PFV and mean-PFV (max-PFV 26.7 +/- 3.2 and 25.7 +/- 3.4 cm/s respectively; mean-PFV 22.9 +/- 2.8 and 22.4 +/- 3.8 cm/s respectively). The LC-patients' values (max-PFV 19.3 +/- 3.5; mean-PFV 16.9 +/- 2.9) were significantly lower than those of the normal subjects (P less than 0.001) and of the CH-patients (P less than 0.001). Considering the normal max-PFV to be in the range 20-33.1 cm/s (mean +/- 2 s.d. of the normal subjects, 95% confidence limits), max-PFV was reduced in 0/50 normal subjects, 1/58 CH-patients and 39/59 LC-patients (66.1% sensitivity; 98.2% specificity). In conclusion, the duplex-Doppler measurement of PFV is of great interest in the diagnostic study of patients with suspected chronic compensated liver disease and in the early diagnosis of cirrhosis. A low max-PFV is a reliable pointer to liver cirrhosis, whereas a normal max-PFV indicates a non-cirrhotic liver disease but is less probative. Each centre should standardize normal PFV values in order to establish their own threshold value for diagnosing liver cirrhosis. PMID- 1515564 TI - Tattooing and hepatitis B infection. AB - To determine the prevalence of HBV carrier status in tattooed persons, 200 healthy, tattooed volunteers and 200 non-tattooed volunteers to match the first group for age, sex and ethnic group were screened. Prevalence of HBsAg in tattooed and non-tattooed volunteers was 19.5 and 9% respectively, which was a statistically significant difference (P less than 0.01). There was no difference in the prevalence in various age groups, ethnic groups, or sex, between the two groups. PMID- 1515565 TI - Duplex-Doppler ultrasonography in the evaluation of cirrhotic patients with portal hypertension and in the analysis of their response to drugs. AB - Sixteen patients (15 males, aged 48-70) affected by liver cirrhosis and oesophageal varices were subjected to duplex-Doppler ultrasonographic study (DDUS). Four patients (three with a portal thrombosis and one with a hepatofugal portal flow) were excluded from the subsequent pharmacological test. The twelve remaining patients took part in a double blind cross-over study that evaluated the variations of heart rate (HR), mean systemic arterial pressure (SAP), portal vein diameter (PVD), maximal and mean portal flow velocity (PFV) after the administration of either 40 mg of propranolol or placebo per os, on two consecutive days. Propranolol caused no significant variation in mean SAP and in PVD, whereas it reduced the HR from 67.7 +/- 8.0 to 58.4 +/- 7.0 beats/min (mean +/- s.d.; P less than 0.001); the maxPFV dropped from 18.2 +/- 5.4 to 14.0 +/- 3.7 cm/s (P less than 0.001) and the meanPFV dropped from 15.3 +/- 4.1 to 13.2 +/ 3.1 cm/s (P less than 0.005). No significant variation was observed with placebo. After propranolol administration eight patients exhibited a significant maxPFV decrease, whereas the other four patients exhibited only a drop in HR, suggesting either drug inefficacy, inappropriate dosage or inadequate duration of treatment. DDUS is the only non-invasive method for the examination of the portal vein system.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1515566 TI - Striking variability of hepatic copper levels in fulminant hepatic failure. AB - Two cases of acute hepatic failure are reported in which the diagnosis of Wilson's disease was considered because of low serum ceruloplasmin, low serum copper levels and high 24 h urinary copper. Case 1 had Kayser-Fleischer rings, haemolysis and a high 24 h urinary copper, and so Wilson's disease was confidently diagnosed. Case 2 had high urinary copper excretion, but [64Cu] study indicated a 24:2 h ratio of 0.7 and made the diagnosis of Wilson's disease uncertain. Both patients underwent orthotopic hepatic transplantation, and multiple biopsies were taken from the resected specimen in order to estimate hepatic copper levels. In both cases, hepatic copper levels revealed considerable variation: 0.8-5.2 mumol/g dry wt (case 1) vs 0.02-12.65 mumol/g dry wt (case 2). In case 1, only two of 14 levels were within the diagnostic range for Wilson's disease (greater than 4 mumol/g dry wt), whereas hepatic copper levels in case 2 were in the Wilsonian disease range in three of 16 specimens. These results were in contrast to uniformly high hepatic copper levels in one patient with established cirrhosis secondary to Wilson's disease and two cases of primary biliary cirrhosis. This report indicates that hepatic copper levels vary greatly in acute liver failure, and that estimates from a single biopsy specimen may be misleading as to the cause of the underlying liver disease. PMID- 1515567 TI - Effects of a gastric mucosal protecting agent in rats with liver cirrhosis. AB - Male Sprague-Dawley rats were fed a 0.1% ethionine-added choline-deficient diet for 8 weeks to induce liver cirrhosis. At the same time 100 mg/kg/day teprenone was administered orally in order to evaluate its effects on the liver and gastric mucosal blood flow. Blood flow increased not only in gastric mucosa but also in liver tissues in the teprenone group. Serum transaminase levels and histopathologic findings of the liver also improved. These findings suggest that teprenone alleviates hepatocellular injuries. This effect may be partly attributable to cytoprotective effects of the catenoid isoprenoid moiety of teprenone on liver cells. PMID- 1515568 TI - The interferon-alpha 2b gene in Japanese patients with chronic viral hepatitis who developed antibodies after treatment with recombinant interferon-alpha 2a. AB - DNA was extracted from leucocytes of 23 Japanese patients with chronic viral hepatitis who received treatment with recombinant interferon-alpha 2a (IFN-alpha 2a) and nine healthy controls, as well as eight human cell lines of Caucasian or African origin. A part of the gene encoding IFN-alpha 2 was amplified by polymerase chain reaction and the sequence of nucleotides 1-231 was determined. Interferon-alpha 2a, -alpha 2b and -alpha 2c genes were tested for in five clones each from a patient or control, or a cell line, based on adenine or guanine at nucleotide positions 68 and 101. The IFN-alpha 2b gene was detected in all 160 clones from 23 Japanese patients and nine controls, but the IFN-alpha 2a or alpha 2c gene was not found in any. Of five cell lines derived from Caucasians, four exhibited only the IFN-alpha 2b gene, while the remaining one exhibited both IFN-alpha 2a and -alpha 2b genes. Of three cell lines derived from Africans, one each showed only the IFN-alpha 2b or -alpha 2c gene, and the remaining one both IFN-alpha 2b and -alpha 2c genes. The 23 patients with the IFN-alpha 2b gene and chronic viral hepatitis included 10 who developed antibodies against IFN after treatment with recombinant IFN-alpha 2a. These results indicated a distinct geographical distribution of the three IFN-alpha 2 genes, and suggested the use of a recombinant IFN-alpha 2 preparation in agreement with the IFN-alpha 2 gene possessed by the recipient to avoid antibody responses. PMID- 1515569 TI - Genetic and acquired factors that influence individual susceptibility to alcohol associated liver disease. PMID- 1515570 TI - Duodenal ulcer in China. AB - The author visited China in 1981 and 1984 and obtained data comparing the incidence of duodenal ulcer in the rice eating districts of the south with the incidence in the wheat, maize and millet eating areas of the north. The evidence suggested a higher prevalence of duodenal ulcer in the rice eating areas than in the wheat eating areas, and a low prevalence in association with millet eating. However, the differences were less marked than between similar rice and wheat eating areas of India. It is suggested that the lower prevalence of duodenal ulcer in the wheat eating areas of north India compared with the rice eating areas of south India may be due in part to the mucosal protective effect of wheat bran in the unrefined wheat that is used in making chappatis. In China white refined flour is used in the making of steamed bread with the loss of any protective effect of wheat bran. PMID- 1515571 TI - Mono-arthritis in a chronic hepatitis B patient after alpha-interferon treatment. AB - A 28 year old woman with hepatitis B (HB) related chronic active hepatitis was treated with a 12 week course of alpha-interferon (alpha-IFN). She developed acute mono-arthritis 1 week after completion of treatment. Her rheumatoid factor (RF) was positive before alpha-IFN and fell steadily during therapy. This was followed by a rebound of RF level with the associated arthritis occurring 1 week after completion of the course of alpha-IFN. In absence of any medication RF gradually fell and became negative at the end of 1 year. This observation is thought to be related to the immunomodulatory effect of alpha-IFN either directly on RF production or indirectly through the control of hepatitis. PMID- 1515572 TI - Management of ascites. PMID- 1515573 TI - Morphological correlates of protein kinase C induced potentiation in the chick brain slice. AB - Continuous perfusion of a chick brain slice with 10 microM 4 beta phorbol 12,13 diacetate (PDAc) produces a significant increase in the amplitude of the response to electrical stimulation at 0.1 Hz recorded within the intermediate and medial part of the hyperstriatum ventrale (IMHV). This PDAc-induced potentiation and that induced by tetanising stimulation appear to share similar mechanisms. Quantitative electron microscopy of synapses within the IMHV from slices in which a PDAc induced potentiation had been produced 30 minutes earlier showed that compared with control slices there was a significant increase in the size of the postsynaptic density of spine synapses. The change was greater in magnitude than that observed in spine synapses following tetanically induced potentiation. No other synaptic parameters were affected. PMID- 1515574 TI - Protein kinase activity and synaptic plasticity in a chick brain slice. AB - In an in vitro slice preparation of the chick brain it is possible to record responses to single electrical stimuli from within the intermediate and medial part of the hyperstriatum ventrale (IMHV), a region known to be involved in learning. The amplitude of such responses is significantly increased by superfusion of the slice with 10 microM 4 beta-phorbol 12,13 diacetate (PDAc), a phorbol ester which stimulates protein kinase activity. The ability of PDAc to induce potentiation is greatest in chicks less than 6 days old. Administration of the kinase antagonist H7 prevents the induction of persistent potentiation and in fact produces a long lasting depression of response amplitude. H7 also produces a short term increase in excitability within the IMHV and results in increased expression of N-methyl-D-aspartate receptor activity. PMID- 1515575 TI - Spontaneous regeneration of adult rat retinal ganglion cell axons in vivo. AB - The superior brachial region of the left optic tract was lesioned in adult rats and foetal tectal tissue was implanted into the lesion site. The retinal projection from the contralateral (right) eye was examined 2 to 8 months later. In the majority of animals, retinal ganglion cell (rgc) axons were found to regenerate through cellular membranes which formed over the lesion. Axon growth could extend for up to 5 or 6 mm. Surviving tectal grafts were identified in all host rats. In animals in which regrowing rgc axons contacted tectal grafts, axons were found to innervate selectively their appropriate target regions within the graft neuropil. PMID- 1515576 TI - Induction of social dominance by L-dopa treatment in Arctic charr. AB - The effect of L-dopa on social dominance was studied in the juvenile Arctic charr (Salvelinus alpinus). L-dopa is the immediate precursor of dopamine, a neurotransmitter that has been connected with aggressive behaviour in fish as well as mammals. Arctic charr were placed in pairs. One individual in each pair was given L-dopa orally, while the other was given vehicle. The results showed that 18 out of 22 fish given 10 mg L-dopa kg-1 became dominant (p = 0.004, binomial test). A higher dose of L-dopa (200 mg kg-1) induced dyskinesia. L-dopa was found to cause a dose-dependent increase in the brain levels of dopamine and 3,4-dihydroxyphenylacetic acid (DOPAC, a major dopamine metabolite), as well as an increase in the DOPAC/dopamine ratio (an index of dopaminergic activity). PMID- 1515577 TI - Expression of a single dopamine transporter cDNA can confer two cocaine binding sites. AB - Radiolabeled cocaine analogs can bind to low and high affinity sites on striatal dopamine transporters (DAT). Recently, a cDNA encoding a rat brain dopamine transporter pDAT1 has been cloned. COS cells transfected with the pDAT1 in a eukaryotic expression vector express both a high (KD = 3.4 nM) and low affinity (KD = 163.6 nM) cocaine binding sites, suggesting that both sites are provided by a single gene product. PMID- 1515578 TI - CaBP D-28k and NADPH-diaphorase coexistence in the magnocellular neurosecretory nuclei. AB - Coexistence of the calcium binding protein calbindin D-28k and NADPH-diaphorase activity was studied in the magnocellular secretory nuclei of the rat hypothalamus using both immunocytochemical and histochemical techniques. Coexistence was found in all the nuclei considered (supraoptic, paraventricular, circularis and fornicals nuclei) with the exception of the hypothalamic area situated between the supraoptic and the paraventricular nuclei. Since both stainings are reliable markers, not based upon the physiological characteristics at a given moment, our study provides a further characterization of the neurons in the magnocellular neurosecretory nuclei. PMID- 1515579 TI - Variations of pre-proNPY mRNA in the arcuate nucleus during the rat estrous cycle. AB - In order to assess the role of sex steroids on the regulation of neuropeptide Y (NPY), levels of pre-proNPY mRNA were measured by in situ hybridization in the rat arcuate nucleus during the estrous cycle. Pre-proNPY mRNA levels were quite stable during diestrus I, diestrus II and the morning of the proestrus, and were 25-30% higher during the afternoon of the proestrus and during the day of the estrus. These data suggest that NPY synthesis is modulated by variations in the circulating levels of sex steroids. Also the excellent correlation between the variations in the levels of pre-proNPY mRNA and those of luteinizing hormone releasing hormone (LHRH) mRNA observed throughout the estrous cycle supports the hypothesis that NPY might be involved in the regulation of LHRH secretion. PMID- 1515580 TI - Noradrenergic inputs enhance the response of neurosecretory cells to osmotic stimulation. AB - Extracellular recordings from neurosecretory cells in the hypothalamic paraventricular nucleus (PVN) displayed either an excitation or no response following electrical stimulation (5 Hz) of the A1 noradrenergic region of the ventrolateral medulla, and exhibited either an increase or no effect in neuronal activity in response to intracarotid injections of hypertonic saline (0.2 M, 0.05 ml). The neurons responded to both the electrical and osmotic stimuli, A1 region stimulation at the subthreshold current (80-90% of the threshold required to evoke the response) significantly enhancing the facilitatory response caused by the osmotic stimulation. These results suggest that the A1 region may serve to potentiate the responsiveness of PVN neurosecretory cells in response to changes in plasma osmolality. PMID- 1515581 TI - Age-dependent changes in position sense in human proximal interphalangeal joints. AB - Using a position matching paradigm, the ability of subjects to detect displacements at the proximal interphalangeal joint of the index finger was tested. These displacements were imposed at an angular velocity of 2 degrees per minute which is below the threshold for movement detection. An older group of subjects whose mean age (+/- s.e.m.) was 56.6 +/- 3.2 years showed significantly poorer performance in detecting the position of the index finger than a group of younger subjects (23.7 +/- 0.5 years). Analysis of the correlation between age and magnitude of matching error gave a positive correlation coefficient of 0.466 which was statistically significant. However, there was no systematic bias in judgements of finger position by the older group. These results indicate that the sense of position of the fingers decrements with age. PMID- 1515582 TI - Dopamine fiber detection by [11C]-CFT and PET in a primate model of parkinsonism. AB - Monkeys were treated on two regimens of 1-methyl-4-phenyl-1,2,3,6 tetrahydropyridine (MPTP) injections to achieve dopamine fiber degeneration of differing severities. A rapid treatment regimen produced a severe parkinsonian syndrome, whereas an intermittent regimen did not cause locomotor symptoms to appear up to 25 weeks. High resolution PET scanning of dopamine nerve terminals revealed that the specific binding of the dopamine transporter [11C]-WIN 35,428 ([11C]-CFT) was diminished by 94% (caudate nucleus) and by 93% (putamen) in the symptomatic monkey. Decreases of 65 and 67% were detected in these regions in the non-symptomatic monkey. Post-mortem immunocytochemical evaluation of presumed dopamine fibers by tyrosine-hydroxylase showed similar reductions in the symptomatic animal. PMID- 1515583 TI - Trophic influences of excitatory and inhibitory synapses on neurones in the auditory brain stem. AB - The effects of a reduction during development of excitatory and inhibitory synaptic input on CNS neurones were studied in the lateral superior olivary nucleus (LSO) of the ferret following neonatal, unilateral cochlear removal. LSO neurones normally receive excitatory input from the ipsilateral ear and inhibitory input from the contralateral ear. After cochlear removal, the ipsilateral LSO was smaller and contained fewer neurones than either the contralateral or the normal LSO. No difference was found between the volume or number of neurones in the latter nuclei. Remaining neurones in the LSO ipsilateral to the removal were smaller than those in the contralateral LSO of the same ferrets. These data show that activity in excitatory pre-synaptic terminals can be sufficient for post-synaptic target maintenance, but that activity in inhibitory terminals alone is not. PMID- 1515584 TI - P2 purinoceptors stimulate inositol phosphate release in the organ of Corti. AB - We examined the effects of purinoceptor agonists on inositol phosphate (IP) release in the guinea-pig organ of Corti. The P2y receptor agonist ATP-gamma-S (200 microM) increased IPs 4-fold; identical concentrations of alpha, beta methylene ATP, a P2x agonist, and adenosine, a P1 agonist, did not significantly affect IP release. In calcium-free incubations, simulated IP release decreased by 35% indicating partial dependence of ATP-mediated phosphoinositide hydrolysis on calcium influx. ATP-stimulated IP release was not enhanced by the cholinergic agonist carbachol known to increase IPs via muscarinic receptors in the organ of Corti. This is consistent with the notion that ATP and carbachol have a common target, most likely outer hair cells. P2 purinoceptors coupled to the phosphoinositide cascade suggest ATP as an afferent neuromodulator or efferent neurotransmitter in the cochlea. PMID- 1515585 TI - M1 and M3 muscarinic receptors: specific roles in sleep regulation. AB - P-fluoro-hexahydro-sila-difenidol hydrochloride (p-F-HHSiD) (15, 30 micrograms) and pirenzepine (7.5, 15, 30 micrograms), which are highly selective M3 and M1 muscarinic antagonists, respectively, were injected intracerebroventricularly into freely moving rats. p-F-HHSiD (30 micrograms) reduced wakefulness (W) (from 34.7 +/- 3.1 to 24.9 +/- 1.3 min) and increased slow wave sleep (SWS) (from 56.7 +/- 2.4 to 67.2 +/- 1.5 min); however, it did not modify desynchronized sleep (DS) latency and percentage in 6 h recordings. W and SWS were not affected by pirenzepine (7.5, 15, 30 micrograms) which decreased significantly DS amount but left unaffected DS latency. The results suggest that each muscarinic receptor subtype may induce different and specific changes in sleep phases and cortical desynchronization processes. PMID- 1515586 TI - In vivo and in vitro NGF studies on developing cerebellar cells. AB - The biological effect of nerve growth factor (NGF) in the early prenatal cerebellar cell was studied in vivo and in vitro with autoradiographic, tissue culture and immunohistochemical techniques. Iodinated NGF (125I-NGF) injected into the cerebella of 16-day-old rat embryos showed accumulation of this ligand in the Purkinje cell layers. The ability of these cells to accumulate NGF lasted to the 19th day of embryonic life. Cerebellar cells isolated from embryos of the same age, but not older embryos, cultured in vitro for two weeks in the presence of NGF, showed morphological characteristics similar to Purkinje-like cells. These findings suggest that NGF exerts a time-limited trophic effect on immature Purkinje cell precursors. PMID- 1515587 TI - Multi-phase expiratory inhibition of phrenic motoneurons in the decerebrate cat. AB - We studied the membrane potential changes of 11 phrenic motoneurons (PMs), located in the C5 portion of the cervical spinal cord, in decerebrate, paralyzed and artificially ventilated cats. Intracellular chloride iontophoresis into PMs could reverse the waves of inhibitory postsynaptic potentials (IPSPs) causing membrane hyperpolarization during expiration. In all PMs, we revealed, in addition to the previously described late expiratory augmenting wave of IPSPs, an early expiratory decrementing wave of IPSPs. Moreover, in three PMs, recorded in two cats exhibiting slow respiratory rhythms, an additional wave of IPSPs was interposed between the early and late ones. The possible origins and roles of these three different waves of inhibition are discussed. PMID- 1515588 TI - Analgesia for tonic pain by self-administered lateral hypothalamic stimulation. AB - The present study was designed to determine if analgesia for tonic pain could be induced with self-administered lateral hypothalamic (LH) stimulation. The majority of studies of LH stimulation employed behaviorally non-contingent stimulation. According to some investigators behaviorally non-contingent LH stimulation might be aversive and consequently yield stress-induced analgesia rather than a primary analgesic effect. Other investigators have reported that non-contingent LH stimulation can be rewarding. Our findings indicate that LH analgesia for tonic pain can be obtained with self-administered LH stimulation. These findings indicate that the analgesia we have obtained in previous work is a primary effect and not dependent on stress induced by behaviorally non-contingent LH stimulation. PMID- 1515589 TI - Application of testosterone accelerates oligodendrocyte maturation in brains of zebra finches. AB - The effects of exogenously applied hormones on glial cell maturation of telencephalic song motor centers, midbrain and cerebellar structures was studied in juvenile male zebra finches. Testosterone was administered and the development of oligodendrocytes was studied using immunochemistry and computer aided image analysis on silver impregnated brain sections. A testosterone induced acceleration of oligodendrocyte maturation could be detected in several brain areas by using the monoclonal antibody O 10 recognizing an oligodendrocyte specific cell surface antigen and by the silver impregnation for myelin. The increase in myelin density was higher in the testosterone treated animals than in the control animals in the forebrain and in the cerebellum, whereas two regions in the midbrain showed no difference between treated and controls. PMID- 1515590 TI - Two classes of potassium currents in Xenopus muscle cells in young cultures. AB - The aim of the present study was to determine if both inactivating and non inactivating potassium currents occur in skeletal muscle cells at early times in culture. Whole cell current was recorded from embryonic muscle cells within 4-10 h of plating. We found that in the cells which had an outward current, half had a current that did not inactivate and half had a current that inactivated during a maintained depolarization (100 ms). The two groups of cells did not differ in their age in culture or resting membrane potential. The results indicate that Xenopus skeletal muscle cells can acquire both types of outward potassium current early in culture life. PMID- 1515591 TI - First isolation of gamma-L-glutamyl-gamma-aminobutyric acid from bovine brains. AB - We had obtained some immunohistochemical indications which suggested that peptide(s) containing GABA at the C-terminal could exist in specific neurons in brains. We therefore sought such GABA conjugate(s) by isolating an acidic GABA dipeptide from bovine brains and determined its structure as gamma-L-glutamyl gamma-aminobutyric acid (gamma-L-Glu-gamma Abu:GluGABA). Its gamma-linkage was determined by a mass-spectrometric (B/E linked scan SIMS) analysis; its chirality was established by a chiral column HPLC technique. This peptide is the first acidic GABA-peptide recognized in brain and the first brain peptide containing GABA at the C-terminal. PMID- 1515592 TI - Biocytin injections produce selective neuronal labeling in the rat CNS. AB - Large injections of biocytin into the lateral ventricle or brain resulted in the labeling of particular neuronal subpopulations in the rat CNS. Localization was accomplished using the avidin-biotin-peroxidase technique. In many cases the staining of neurons was totally complete and resembled that obtained with the Golgi technique. Regions containing labeled cells included the olfactory bulb, cerebral cortex, hippocampus, amygdala, striatum, hypothalamus, superior and inferior colliculi, cerebellar cortex, and dorsal horn of the spinal cord. Only particular cell types were labeled in each of these regions. The results of this study suggest that there is selective uptake and/or retention of biocytin, or a biotinylated metabolite of biocytin, by subpopulations of CNS neurons. PMID- 1515593 TI - Chol-1 is a cholinergic marker in the human central nervous system. AB - The cholinergic-specific gangliosides Chol-1 alpha and beta were detected in human brain and spinal cord by immune staining of thin-layer chromatography (TLC) plates on which ganglioside extracts had been separated. The colocalization of choline acetyltransferase (ChAT) and the Chol-1 antigens in ventral horn motoneurons was demonstrated immunocytochemically. In analytical studies, Chol-1 was found to be more concentrated in dorsal cord than ventral but the reverse was true of ChAT. This difference was explained by differences in the subcellular location of the two markers. Within each region of the thoracic cord the levels of ChAT and Chol-1 in different cords showed covariance. The expected fall of ChAT and Chol-1 in amyotrophic lateral sclerosis (ALS) cords was not seen and possible reasons for this are discussed. PMID- 1515594 TI - The effects of two different inhibitors of PNMT and their interactions with ethanol. AB - The effects of two structurally different inhibitors of phenylethanolamine-N methyltransferase, LY 134046 and CGS 19281A were investigated in a holeboard test of directed exploration and locomotor activity. Both compounds dose-dependently reduced exploratory head-dipping without affecting locomotor activity. The interaction of each drug with ethanol was also studied by testing the ataxia. Administration of these compounds had differential effects in a test of ethanol induced ataxia. LY 134046 significantly attenuated ethanol-induced ataxia whereas CGS 19281A was without effect or (at 50 mg kg-1) potentiated ethanol's effect. These results suggest that the ethanol attenuating properties of LY 134046 may not solely be due the inhibition of PNMT and that its alpha 2-adrenoceptor blocking properties may be playing a role. PMID- 1515595 TI - Recovery of nucleus basalis cholinergic neurons by grafting NGF secretor fibroblasts. AB - The effects of nerve growth factor (NGF) secreted from genetically modified fibroblasts was studied in vitro, using dissociated septal cells and in vivo, in rats bearing unilateral cortical devascularizing lesions. Transfected fibroblasts expressing nerve growth factor (NGF) were co-cultured with rat embryonic cholinergic cells of the septal region. This in vitro system showed that NGF secretor cells produce biologically active NGF, as determined by increasing choline acetyltransferase (ChAT) activity in septal culture after seven days. The potential therapeutic value of applying grafts of transfected fibroblasts expressing NGF in the model of retrograde atrophy of cholinergic neurons of the nucleus basalis magnocellularis (NBM) was assessed following partial devascularizing lesions of the cerebral cortex. We observed an increase in ChAT activity in the remaining cortex and a partial protection of the ipsilateral NBM, as determined by morphometric and biochemical studies. PMID- 1515596 TI - Presynaptic calcium transients evoked by paired-pulse stimulation in the hippocampal slice. AB - The fluorescent dye Calcium Green and optical recording techniques were used to record intracellular Ca2+ transients resulting from paired-pulse stimulation in stratum moleculare of area CA1 in guinea-pig hippocampal slices. Presumed presynaptic calcium transients were recorded while glutamatergic synaptic transmission was blocked by kynurenic acid. Peak responses to paired-pulses (10 160 ms interval) were higher than responses to single pulses of same stimulation strength (42-23% increase). The isolated response to the second pulse, however, was of smaller magnitude in comparison to the first one; the difference in magnitude depended on the interstimulus interval. Thus, the residual presynaptic free calcium concentration may be responsible for paired-pulse facilitation of synaptic transmission in hippocampus. At the same time, a use-dependent inactivation of presynaptic calcium channels may occur. PMID- 1515597 TI - Respiration-related neurons recorded in the deep cerebellar nuclei of the alert cat. AB - The activity of deep cerebellar nuclei neurons was recorded in the alert cat and related to the respiratory cycle. Respiration-related neurons (RRNs, n = 29), located in the rostral fastigial and interpositus nuclei, were classified as inspiratory (24%) or expiratory (76%). Nine RRNs were antidromically activated from the red nucleus, but none from the inferior olive. Half of the RRNs showed well defined proprioceptive inputs of a rather broad origin. Other RRNs (27%) showed a respiration-related pattern independent of respiratory movement performance. Repeated electrical stimulation of the inferior olive exerted a synchronizing effect on the firing rate of 24% of the RRNs. It is proposed that cerebellar nuclear RRNs are involved in locomotor re-adjustments of the respiratory musculature. PMID- 1515598 TI - Oscillatory activity is not evident in the primate temporal visual cortex with static stimuli. AB - It has been suggested in studies in the visual system of anaesthetized cats that oscillatory activity with a frequency of 40-60 Hz occurs during the presentation of moving visual stimuli and reflects a synchronization process between neurons that could implement the binding together of related neurons into different sets. We found no evidence for such oscillations in the inferior temporal visual cortex and related areas of awake macaques fixating effective static visual stimuli, which for the neurons analysed were faces. We put forward the possibility that temporal synchronization between neurons to implement binding may not be generally used in the visual system as a solution to the binding problem, at least when static objects are being processed and recognised in higher parts of the visual system. PMID- 1515599 TI - Comparison of regions coding for tRNA(His) genes of mitochondrial and chloroplast DNA in sunflower: a proposal concerning the classification of 'CP-like' tRNA genes. PMID- 1515600 TI - A T-DNA transfer stimulator sequence in the vicinity of the right border of pRi8196. AB - An 8 bp sequence repeated 6 times is present to the right of the mannopine type pRi8196 T-DNA right-border sequence. Experiments were designed to test whether these repeats have a role in T-DNA transfer. Several constructs in which different lengths of pRi8196 right-border region were linked to the cucumopine synthesis gene on an Agrobacterium-Escherichia coli shuttle vector were made. The recombinant plasmids were tested for their efficiency to act as a source of T-DNA in a binary system in which a wild-type Ri plasmid provided virulence and root inducing functions. The T-DNA transfer efficiency of the constructs was assessed by computing the relative frequency of roots containing cucumopine. Depending on the Ri plasmid used as source of virulence functions, a high level of T-DNA transfer was observed only if 6 (pRi8196) or 5 (pRiA4) repeats were present. These results were confirmed by looking for single-stranded T-DNA molecules (T strands) in bacteria induced for virulence. The repetition of the 8 bp unit was named 'T-DNA transfer stimulator sequence' (TSS). PMID- 1515601 TI - Transfection of heteroduplexes containing uracil.guanine or thymine.guanine mispairs into plant cells. AB - We have compared the fate of U.G mispairs or analogous T.G mispairs in DNA heteroduplexes transfected into tobacco protoplasts. The heteroduplex DNA consisted of tomato golden mosaic virus DNA sequences in the Escherichia coli vectors pUC118 or pUC119. After transfection, the mismatched U residues were lost with an efficiency of greater than 95%, probably as a result of the uracil-DNA glycosylase pathway for excision of U residues in any sequence context. In contrast to the preferential removal of the mispaired U residues, biased removal of T residues from analogous heteroduplexes was not seen in the transfected plant cells. Also, we investigated the effect of extensively methylating one strand of the heteroduplex DNA used for transfection. Surprisingly, such methylation resulted in highly biased loss of the mismatched base from the 5-methylcytosine rich strand of T.G-containing heteroduplexes. PMID- 1515603 TI - Nucleotide sequence and temporal regulation of a seed-specific Brassica napus cDNA encoding a stearoyl-acyl carrier protein (ACP) desaturase. AB - The nucleotide sequence is reported for a cDNA containing the entire coding region of a stearoyl-ACP desaturase (EC 1.14.99.6) from Brassica napus L. cv. Jet neuf. The cDNA was obtained from a library constructed from poly(A)+ RNA purified from embryo tissue. The derived amino acid sequence demonstrates substantial similarity with those from other plant delta 9-desaturases. Comparative RNA-dot blot analyses using the delta 9-desaturase cDNA and a rapeseed oleosin cDNA as probes showed that although both these transcripts were seed-specific, they exhibited distinct patterns of temporal regulation. The desaturase message was induced by 25 days after anthesis (DAA), peaking at 45 DAA but decreasing considerably thereafter. In contrast, the oleosin transcript did not increase until 45-50 DAA, reaching a peak much later at about 70 DAA. PMID- 1515604 TI - Nucleotide sequence of the internal transcribed spacer region of rDNA in diploid wheat, Triticum speltoides L. (Tausch) Gren. ex Richter (Gramineae). PMID- 1515602 TI - Intracellular trafficking of secretory proteins. PMID- 1515605 TI - Nucleotide sequence of the internal transcribed spacer region of rDNA in wheat, Triticum aestivum L. (Gramineae). PMID- 1515606 TI - Nucleotide sequence of the internal transcribed spacer region of rDNA in mountain rye, Secale montanum Guss. (Gramineae). PMID- 1515607 TI - Nucleotide sequence of the internal transcribed spacer region of rDNA in the primitive oat species, Avena longiglumis Durieu (Gramineae). PMID- 1515608 TI - Nucleotide sequence of the internal transcribed spacer region of rDNA in barley, Hordeum vulgare L. (Gramineae). PMID- 1515609 TI - Molecular cloning of phenylalanine ammonia-lyase cDNA from Pisum sativum. PMID- 1515610 TI - Potato granule-bound starch synthase promoter-controlled GUS expression: regulation of expression after transient and stable transformation. AB - Chimaeric genes of promoter sequences from the potato gene encoding granule-bound starch synthase (GBSS) and the beta-glucoronidase (GUS) reporter gene were used to study GBSS expression and regulation. Analysis of stable transformants revealed that a GBSS promoter sequence of 0.4 kb was sufficient to result in tissue-dependent GUS expression: levels in stably transformed microtubers exceeded levels in corresponding leaves by orders of magnitude. GBSS-GUS constructs could be transiently expressed in leaf protoplasts from wild-type and amylose-free potato lines, etuberosum Solanum brevidens, Nicotiana tabacum and Arabidopsis thaliana. Transient expression levels in potato leaf protoplasts were clearly lower than in corresponding suspension cell protoplasts. This lower expression in leaf protoplasts could not be elevated by increasing DNA concentrations during transfection. Light incubation of electroporated suspension cell protoplasts reduced transient GBSS-GUS expression, whereas incubation of transfected protoplasts in media with different sucrose concentrations did not affect transient expression levels. However, electroporated protoplasts, isolated from suspensions, which had been grown on media with increasing amounts of sucrose showed a sucrose concentration-dependent transient expression profile. This indicates that studying GBSS regulation by transient expression experiments needs pre-treatment of the protoplast source. Sequence data of the GBSS promoter were compared to those of two other potato alleles. PMID- 1515611 TI - A simple and efficient method for purification of multiple cDNAs by using a single hybridization step on nylon discs. PMID- 1515612 TI - The cab-m7 gene: a light-inducible, mesophyll-specific gene of maize. AB - Southern blot analysis has revealed the existence in maize of perhaps 12 members of the nuclear cab multigene family encoding the chlorophyll a- and b-binding proteins of the photosystem II light-harvesting complex. Hybridization with 3' probes derived from unsequenced cDNA clones showed that six members of this family differ from one another with respect to expression in mesophyll and/or bundle sheath cells and regulation by light. An additional member of this family, designated cab-m7, that encodes a 28 kDa primary translation product has now been identified. It has been cloned from a maize genomic library and sequenced to begin to define the bases for differences in the expression of these genes. This cab gene is shown to be strongly preferentially expressed in the mesophyll (vs. bundle sheath) cells of maize. Furthermore, the gene is photo-responsive; although small amounts of cab-m7 mRNA are present in etiolated leaves, the mRNA pool is 8-fold larger after six hours of illumination. DNA sequences upstream of the cab-m7 gene resemble those found in the 5'-flanking regions of some other plant genes. PMID- 1515613 TI - Arabidopsis thaliana small subunit leader and transit peptide enhance the expression of Bacillus thuringiensis proteins in transgenic plants. AB - The expression of the modified gene for a truncated form of the cryIA(c) gene, encoding the insecticidal portion of the lepidopteran-active CryIA(c) protein from Bacillus thuringiensis var. kurstaki (B.t.k.) HD73, under control of the Arabidopsis thaliana ribulose-1,5-bisphosphate carboxylase (Rubisco) small subunit ats1A promoter with and without its associated transit peptide was analyzed in transgenic tobacco plants. Examination of leaf tissue revealed that the ats1A promoter with its transit peptide sequence fused to the truncated CryIA(c) protein provided a 10-fold to 20-fold increase in cryIA(c) mRNA and protein levels compared to gene constructs in which the cauliflower mosaic virus 35S promoter with a duplication of the enhancer region (CaMV-En35S) was used to express the same cryIA(c) gene. Transient expression assays in tobacco protoplasts and the whole plant results support the conclusion that the transit peptide plus untranslated sequences upstream of that region are both required for the increase in expression of the CryIA(c) protein. Furthermore, the CaMV-En35S promoter can be used with the Arabidopsis ats1A untranslated leader and transit peptide to increase expression of this protein. While subcellular fractionation revealed that the truncated CryIA(c) protein fused to the ats1A transit peptide is located in the chloroplast, the increase in gene expression is independent of targeting of the CryIA(c) protein to the chloroplast. The results reported here provide new insight into the role of 5' untranslated leader sequences and translational fusions to increase heterologous gene expression, and they demonstrate the utility of this approach in the development of insect-resistant crops. PMID- 1515615 TI - Bibliographic update: platelet-derived growth factor. PMID- 1515614 TI - Peptide growth factors and their interactions during chondrogenesis. AB - Peptide growth factors have been implicated in three aspects of cartilage growth and metabolism; the induction of mesoderm and differentiation of a cartilaginous skeleton in the early embryo, the growth and differentiation of chondrocytes within the epiphyseal growth plates leading to endochondral calcification, and the processes of articular cartilage damage and repair. Three peptide growth factor classes have been strongly implicated in these processes, the fibroblast growth factor family (FGF), the insulin-like growth factors (IGFs) including insulin, and transforming growth factor-beta (TGF-beta) and related molecules. Each of these peptide groups are expressed in the early embryo. Basic FGF, TGF beta and the related activin have been shown to induce the appearance of mesoderm from primitive neuroectoderm. TGF-beta and related bone morphometric proteins can induce the differentiation of cartilage from primitive mesenchyme, and together with basic FGF and IGFs promote cartilage growth. Each class of growth factor is expressed within the epiphyseal growth plate where their autocrine/paracrine interactions regulate the rate of chondrocyte proliferation, matrix protein synthesis and terminal differentiation and mineralization. Basic FGF may prove useful in articular cartilage repair, while basic FGF, IGFs and TGF-beta are among a number of growth factors and cytokines that have been implicated in cartilage disease. PMID- 1515616 TI - [Damage to the remaining teeth from displaced upper canines]. AB - 25 patients with 35 retained upper canines were examined by high resolution CT; only 5 patients did not show evidence of damage to the remaining teeth. 8 patients showed resorption related to medial and lateral incisors. 19 teeth were in contact with the crowns of the displaced canines and were therefore liable to damage. The average extent of the resorption was 4.5 mm. Contact between teeth was demonstrable by means of two consecutive CT cuts. PMID- 1515617 TI - [The magnetic resonance tomography of intracranial ependymomas. Their clinical appearance and comparison with computed tomography]. AB - The MRT and CT images of histologically confirmed intracranial ependymomas in 10 patients have been compared. All tumours were demonstrated by CT and MRT. The solid portions of the tumours showed variation in density on CT (hypodense, isodense, hyperdense, or mixed), whereas there was uniform signal intensity on MRT (T1 weighted: hypointense, T2 weighted: hyperintense). Cystic portions of the tumours (6 patients) were shown equally well by both procedures, calcifications were only shown by CT. All ependymomas were related to the ventricles. On unenhanced CT only 3 tumours were clearly delineated, whereas MRT defined all tumours satisfactorily. The significant advantage of MRT is better topographic demonstration of the tumour. PMID- 1515618 TI - [Intracranial aneurysms. A comparison between magnetic resonance tomography and arteriography]. AB - 42 MRI of 36 patients with cerebral aneurysms were analysed retrospectively and compared with selective angiography. 92% of aneurysms proven by angiography were also detected by MRI. The smallest and surgically confirmed aneurysms had a diameter of 2-3 mm on MRI. 3 aneurysms were only demonstrated by selective angiography (8%). This concerned 5 mm sized aneurysms located at the anterior communicating artery (2) and middle cerebral artery (1). On the other hand 2 thrombosed aneurysms were only delineated by MRI (6%). Because partial thrombosis could not be demonstrated by angiography extensions of aneurysms were underestimated in 44% (n = 16) angiographically. A 2.5 cm sized lobulated aneurysm of the internal carotid artery was initially evaluated by MRI as being thrombosed subtotally, due to flow-phenomena. Angiography though showed a wide perfused lumen without visible thrombosis. A progressive thrombosis of a mycotic aneurysm of the internal carotid artery was shown by MRI during septic thrombosis of the cavernous sinus. In this case the number of angiographic controls could be reduced by use of MRI. Nevertheless, MRI was not able to substitute selective angiography, especially to exclude under 6 mm sized cerebral aneurysms. MRI could not demonstrate clearly the vessels in the neighbourhood of saccular aneurysms preoperatively. PMID- 1515619 TI - [Primary and secondary tethered cord syndromes. Their nuclear magnetic tomographic diagnosis and comparison with the surgical findings in 40 patients]. AB - The MRT findings in 40 patients with the tethered cord syndrome (TCS) have been compared with the operative findings. In cases of primary TCS (17 patients), MRT showed a low conus medullaris in 15 cases and this was confirmed surgically in 14. Other abnormal findings were lipomas (MRT 12/operatively 13), diastematomyelia (MRT 2/operatively 2) and thickened filum terminale (MRT 6/operatively 3). In secondary TCS (23 patients) postoperatively adhesions were prominent (MRT 16/operatively 23) while low position of the conus was found by MRT in 19 and surgically in 18 patients. Other findings were lipomas (MRT 5/operatively 6), epidermoids (MRT 2/operatively 2) and diastematomyelia (MRT 2/operatively 0). Agreement between MRT and operative findings regarding fixation of the spinal cord is closer in primary TCS (15/17, 88%) than in secondary TCS (16/23, 69%). PMID- 1515620 TI - [The CT-controlled treatment possibilities in intervertebral disk prolapses]. AB - A CT-controlled method for the treatment of lumbar and cervical disc prolapse is described. Compared with fluoroscopically controlled percutaneous lumbar discectomy, percutaneous treatment of the L5/S1 disc by a dorsal approach is possible even in the presence of high iliac crests, as is described in this paper. In the cervical region the risk of iatrogenic damage is reduced. In a small group of 42 patients, an attempt has been made to remove disc material which is intraforaminal, intraspinal, subligamentous or sequestered. Amongst 79 patients with lumbar and 15 patients with cervical disc prolapse treatment was successful in 85% (after 17 months of observation) and 93% (after 12 months of observation). These figures refer to the early results from a new method. The success of the method will have to be assessed after a larger number of patients has been treated and there has been a longer period of observation. PMID- 1515621 TI - [Automated percutaneous lumbar diskectomy (APLD): the early and late changes in the CT with a clinical correlation]. AB - In 52 out of 162 patients treated, CT changes were measured at early and late stages and correlated with clinical findings. Reduction in height of discs was measured by digital radiography. During early stages 9.6% showed gas collections peripherally and 3.8% centrally. Early and late examination showed uniform reaction in the area of the prolapse: no changes (type I), return to normal findings (type II), diffuse reduction of a broadly based lesion (type III), reduction in focal changes based on a broad lesion (type IV). Early results: 94.3% type I, 3.8% type III, 1.9% type IV. Late results: 55.7% type I, 3.8% type II, 21.2% type III, 19.3% type IV. Maximal reduction of the height of the disc of 10% occurred in 32.6% of cases. There was no meaningful correlation between CT appearances and clinical status. PMID- 1515622 TI - [Quantitatively evaluated dynamic magnetic resonance tomography in chronic polyarthritis of the knee joint. A therapeutic follow-up after intra-articular cortisone application]. AB - 32 patients with chronic polyarthritis were examined by MRT. Following intra articular application of 25 mg prednisolone, 18 patients were re-examined after two of three weeks and 7 out of 18 patients were re-examined after 8 to 16 weeks, both by MRT and clinically. After an initial double echo sequence, we carried out a dynamic series of FLASH measurements (TR 30, TE 10 ms, 70 degrees) following an intravenous bolus of 0.1 mmol gadolinium-DTPA. Single intensity-time curves were treated quantitatively in relation to the pannus, muscles and effusions. Two or three weeks after treatment the curve parameters showed a reduction in pannus vascularisation which remained constant for the 8 to 16 weeks of further observation. Contrast diffusion in the pannus is initially reduced but approaches the early measurements at the time of the second examination. PMID- 1515623 TI - [Comparative studies with quantitative computed tomography and dual-energy x-ray absorptiometry on bone density in renal osteopathy]. AB - Measurements of bone density were carried out in 25 patients on dialysis for terminal renal insufficiency, using quantitative computed tomography (QCT) and dual-energy X-ray absorptiometry (DXA). Unlike in subjects with normal kidneys, there was no significant correlation between these methods in this series. Ten patients showed an increase in bone density of the vertebral spongiosa on QCT measurements, which was interpreted as due to osteosclerotic bone changes in renal osteopathy. QCT showed advantages over DXA in demonstrating these changes. PMID- 1515624 TI - [CT-guided large-bore biopsy of solid non-organ-bound space-occupying lesions in the retroperitoneum]. AB - Seventy-eight solid, non-organic retroperitoneal tumours were biopsied with a 14 gauge Tru-Cut needle in 73 consecutive patients with the exception of one. Adequate material was not obtained in only one patient with the primary known (1.3%). In the adequate material (98.7%), the dignity of all lesions was accurately determined and 93.1% of lesions were accurately classified. Typing accuracy reached 100% in histologically known primaries (n = 31) and 87.8% in histologically unknown primaries (n = 41). A hypertensive crisis and a small haematoma following biopsy of an inadvertent extra-adrenal phaeochromocytoma was the single complication found in this series. An arterial bleeding following biopsy was prophylactically embolised through the biopsy needle. CT-guided large bore biopsy of solid non-organic retroperitoneal tumours is a safe, non-invasive procedure with a high diagnostic yield that obviates the need for open diagnostic procedures in a large number of cases. PMID- 1515625 TI - The clinical value of computed tomography and lymphography in detecting lymph node metastases from epithelial ovarian cancer. AB - We investigated the accuracy of both lymphography and computed tomography (CT) in detecting lymph node metastases in 58 patients with primary epithelial ovarian cancer (group a) and subsequently submitted to surgery including pelvic and/or lumbo-aortic lymphadenectomy. CT accuracy was also investigated in 41 patients with clinically suspected relapse of ovarian cancer (group b). In the first group (a) overall results in the pelvis were, respectively, for lymphography and CT: 94.8 vs 89.6% accuracy, 85.7 vs 57.1% sensitivity, 97.7 vs 100% specificity, 97.7 vs 100% positive predictive value and 95.5 vs 88% negative predictive value. In the lumbo-aortic region, we had: 88.8 vs 86.1% accuracy, 71.4 vs 64.2% sensitivity, 100% specificity and positive predictive value for both techniques, and 84.6 vs 81.6% negative predictive value. In the second group (b) CT accuracy, sensitivity and specificity were 90.2, 80 and 100%, respectively. CT, thanks to its high specificity and positive predictive value, can represent the method of choice for the evaluation of pelvic and lumbo-aortic lymph node metastases in untreated and relapsing ovarian cancer. CT demonstration of lymph node metastases can affect not only lesion staging, but also chemotherapy; different indications for lymphadenectomy may also depend on CT. PMID- 1515626 TI - [Computed tomography: the TNM staging of laryngeal carcinoma]. AB - In 64 patients with malignant lesions of the larynx, CT and microlaryngoscopy (ML) were evaluated in terms of T-staging. Histological information was present in all cases following operation. CT showed an accuracy of 90% in T-staging. ML showed an accuracy of only 71% of correct T-staging. CT is superior to ML particularly in distinguishing between stages T3 and T4 and T1 and T2. CT tends to overestimate tumour stage whereas ML tends to underestimate it. CT was also compared with palpation and sonography as regards N-staging. In this respect sonography has the highest accuracy (94%) followed by palpation (76%) and CT (74%). PMID- 1515627 TI - [The potentials and limits of blood-flow quantification in the peripheral arteries with MRT using a phase-mapping procedure]. AB - MRT is able to demonstrate arteries while MR angiography can quantify blood flow by a noninvasive method. In the present paper blood flow measurements were carried out in four selected cases on the basis of phase mapping. In 3 patients with lesions in the pelvis or thigh, angiography was performed in order to localise the stenosis or occlusion and this was followed by quantitative blood flow measurements. The results showed that angiography may not always provide all necessary information concerning a haemodynamically significant stenosis. The method may also be used for quantifying blood flow in the renal arteries and that it has significant advantages over the colour Doppler method. PMID- 1515628 TI - [Magnetic resonance tomography of the liver with TurboFLASH and segmented acquisition. Fast imaging with flexible image contrast]. AB - The value of a fast imaging sequence in diagnosing focal liver lesions was assessed in 43 patients. The sequence (TurboFLASH with segmented acquisition) allows the acquisition of T1- and T2-weighted images within a breath-hold interval. Lesion-liver contrast was compared with T2-weighted spin-echo, T1 weighted gradient-echo, and single shot TurboFLASH sequences. All lesions that were seen with the latter sequences were also visible on the segmented TurboFLASH images. Contrast on the segmented TurboFLASH images was similar to that of T2 weighted spin-echo sequences and superior to T1-weighted gradient-echo sequences. Signal of fat could be nulled at an inversion time of 10 ms, signal from liver tissue could be nulled at an inversion time of 300 ms. By minimising the liver signal, the lesions could be "highlighted". This was not possible with the other imaging sequences. The segmented TurboFLASH technique allows breath-hold imaging of the liver with arbitrary image contrast. The lesion-liver contrast is comparable to time-consuming T2-weighted spin-echo sequences. PMID- 1515629 TI - [Bilateral duplication of the submandibular gland and the submandibular duct]. PMID- 1515630 TI - [Congenital cystic adenomatoid malformation of the lung. The radiological findings and differential diagnosis]. PMID- 1515631 TI - [The complication of oleothorax]. PMID- 1515632 TI - [Cerebral calcification in chronic lead poisoning]. PMID- 1515633 TI - [CT and MRT of multicystic encephalomalacia in a Reye-like syndrome]. PMID- 1515634 TI - High-dose chemoradiotherapy followed by autologous bone marrow transplantation as consolidation therapy during first complete remission in adult patients with poor risk aggressive lymphoma: a pilot study. AB - Twenty consecutive patients with poor-risk aggressive lymphoma who at presentation either had elevated serum lactic dehydrogenase level (LDH) and any one of the other poor-prognostic features: bulky mass greater than or equal to 10 cm, advanced stage III or IV, and greater than or equal to 2 extranodal sites, or normal LDH level and all other three features, underwent high-dose chemo/radiotherapy followed by unmanipulated autologous bone marrow transplantation (BMT) during their first complete remission. Eighteen had B-cell lymphoma and 2 had T-cell lymphoma. Eleven patients had high-grade (7 immunoblastic, 3 small noncleaved, non-Burkitt's, and 1 Burkitt's) and 9 had diffuse large cell lymphoma. All patients had achieved a complete remission following conventional chemotherapy. Four patients had also received involved field radiotherapy to areas of bulky disease. The preparative regimen consisted of high-dose etoposide 60 mg/kg and cyclophosphamide 100 mg/kg in combination with fractionated total body irradiation (FTBI) 1,200 cGy (15 patients), or single-dose TBI 750 cGy (2 patients), or carmustine 450 mg/m2 (3 patients). All patients tolerated the treatment well and achieved complete hematologic recovery. Three patients have relapsed at days 79, 196, and 401 after transplantation. Seventeen patients (84%) are alive and relapse-free with a median follow-up of 34 months (range 2 to 54). We conclude that high-dose chemo/radiotherapy followed by autologous BMT can be given as consolidation therapy during first remission in these patients with minimal transplant-related toxicity. PMID- 1515635 TI - Disposition of recombinant human granulocyte-macrophage colony-stimulating factor in patients receiving high-dose chemotherapy and autologous bone marrow support. AB - Recombinant human granulocyte-macrophage colony-stimulating factor (rHuGM-CSF) produces dose-related therapeutic and toxic effects; however, relationships between its pharmacokinetics and pharmacodynamics have not been extensively evaluated. The following studies were undertaken to investigate patterns in the disposition of rHuGM-CSF administered after high-dose chemotherapy (cyclophosphamide, cisplatin, carmustine) and autologous bone marrow support. Continuous 14 or 21 day intravenous infusions or daily 4-hour infusions were studied at doses of 1.2 to 19.2 micrograms/kg/d. GM-CSF was measured by an enzyme linked immunosorbent assay from serum and urine samples collected throughout drug administration. Pharmacokinetic parameters were determined by compartmental (4 hour infusions) or noncompartmental methods (continuous infusions). GM-CSF was rapidly eliminated from the serum. Average systemic exposure increased with dose, although wide interpatient variability was evident. Approximately one half of the patients receiving continuous infusions demonstrated increasing GM-CSF clearance that corresponded to the appearance of white blood cells in the periphery. Conversely, clearance decreased in those experiencing renal dysfunction during the infusion. The percentage of a GM-CSF dose found in 24-hour urine collections was substantially reduced in the latter group. A subset of patients who developed renal dysfunction also experienced significant hypotension. Rapidly increasing serum GM-CSF concentrations corresponded to the hypotensive episodes. GM-CSF serum concentration monitoring may be useful for evaluation of therapeutic and toxic effects in patients receiving high-dose chemotherapy with autologous bone marrow support. PMID- 1515636 TI - Effects of interleukin-3 after chemotherapy for advanced ovarian cancer. AB - To define the maximum tolerated dose and to study whether recombinant human interleukin-3 (rhIL-3) reduced chemotherapy-induced neutropenia and thrombocytopenia, 20 chemotherapy-naive patients with advanced ovarian cancer eligible for treatment with 6 cycles of carboplatin-cyclophosphamide every 4 weeks (day 1) were entered in a phase I/II open, single-center trial. Cohorts of five patients received during 7 days 1, 5, 10, or 15 micrograms/kg/d rhIL-3 (days 5 through 11) in cycles 1, 3, and 5 by continuous intravenous (IV) infusion or once daily subcutaneous (SC) administration. In control cycles 2, 4, and 6, no rhIL-3 was administered. rhIL-3 significantly increased the recovery of leukocyte, neutrophil, and platelet counts, especially at 5, 10, and 15 micrograms/kg rhIL-3. rhIL-3 also increased basophil, eosinophil, monocyte, and lymphocyte counts at this dose steps. Effects on reticulocytes were limited. No difference in efficacy between SC and IV rhIL-3 treatment was found. Chemotherapy postponement for insufficient bone marrow recovery was necessary in 22 of 45 control cycles versus 2 of 49 rhIL-3 cycles (P less than .001). Platelet transfusions were required in 7 of 45 control cycles versus 3 of 50 rhIL-3 cycles (P less than .5). rhIL-3 up to 10 micrograms/kg/d could be administered without severe side effects. At 15 micrograms/kg/d, rhIL-3 headache was dose-limiting. Other side effects were fever, flu-like symptoms, nausea, skin rash, flushing, facial erythema, and urticaria. Liver toxicity occurred in rhIL-3 and control cycles. rhIL-3 slightly increased tumor necrosis factor alpha, C-reactive protein, and serum amyloid A plasma levels, whereas no effect on IL-6 plasma levels was observed. rhIL-3 administered SC appears to be an interesting hematopoietic growth factor for reduction of chemotherapy-induced myelotoxicity. PMID- 1515637 TI - Recombinant human granulocyte-macrophage colony-stimulating factor after high dose chemotherapy and autologous bone marrow transplantation with unpurged and purged marrow in non-Hodgkin's lymphoma: a double-blind placebo-controlled trial. AB - The toxicity of autologous bone marrow transplantation (ABMT) is correlated to neutropenia. Although recombinant human granulocyte-macrophage colony-stimulating factor (rhu GM-CSF) seems to hold promise in accelerating neutrophil recovery, few analyses from randomized studies are presently available. Ninety-one patients with non-Hodgkin's lymphoma receiving high-dose ablative chemotherapy followed by ABMT with unpurged or purged marrow were included in a randomized, double-blind, placebo-controlled trial. Forty-four patients received 250 micrograms rhu GM-CSF (Escherichia coli)/m2 and 47 patients received placebo. Treatment was administered daily as continuous infusion from day of ABMT until the absolute neutrophil count (ANC) reached 0.5 x 10(9)/L for 7 days or until day 30, whichever was first. With rhu GM-CSF, 50% of the patients reached an ANC count greater than 0.5 x 10(9)/L at day 14 as opposed to day 21 with placebo (P less than .0001). Patients transplanted with marrow purged by mafosfamide also recovered earlier when treated with rhu GM-CSF (16 v 20.5 days, P = .013). The hospitalization duration was shorter in the rhu GM-CSF group (median, 23 v 28 days, P less than .05). No difference was observed in fever, number of infections, and antibiotic administration between the two groups. The major adverse event ascribed to rhu GM-CSF was a capillary leak syndrome in three patients graded as severe in two patients, moderate in one, and reversible in all three patients. In addition, one patient in the rhu GM-CSF group died suddenly with no explanation. In long term follow-up, the relapse rate was identical in both groups and there was no significant difference in the number of deaths at 1 year (12 with rhu GM-CSF v 9 with placebo), although deaths seemed to occur slightly earlier in the rhu GM-CSF group. We conclude that after ABMT with purged or unpurged marrow, rhu GM-CSF (E coli) significantly reduces neutropenia duration and hospitalization stay. A positive causative relation between the study drug and/or its mode of application with an increased toxicity as compared with GM-CSF from other sources and/or other modes of application cannot be deduced from the experiences in this study. Additional randomized trials would be necessary for an appropriate answer. PMID- 1515638 TI - Effect of adrenergic agents on hematopoiesis after syngeneic bone marrow transplantation in mice. AB - We show that adrenergic agents modulate hematopoietic reconstitution after syngeneic bone marrow transplantation (BMT) in mice. Chemical sympathectomy by 6 hydroxydopamine (6-OHDA) significantly increased the number of peripheral blood leukocytes after syngeneic BMT. The alpha 1-adrenergic antagonist prazosin mimicked and extended the effect of 6-OHDA, with an additional rapid and significant increase of platelets, marrow granulocyte-macrophage colony-forming units, and nucleated spleen cells. Differential leukocyte counts and spleen histology from prazosin-treated mice confirmed that myelopoiesis was greatly enhanced and accelerated. In contrast, the beta-adrenergic blocker propranolol abolished the prazosin-induced increase of platelets. The detailed mechanisms by which prazosin exerts these interesting effects remain to be elucidated. PMID- 1515639 TI - Insulin-like growth factor-I regulates pro-B cell differentiation. AB - Progression of B-lymphocyte development in the bone marrow of postnatal mammals is marked by progressive rearrangement and expression of immunoglobulin (Ig) heavy- and light-chain genes. Following productive VHDJH gene rearrangement in the Ig heavy-chain gene complex, mu-heavy chain is the first Ig gene product expressed in cells committed to the B-lymphoid differentiation pathway. Interleukin (IL)-7 has been shown to stimulate proliferation of pre-B cells following c mu expression and this proliferative stimulus is potentiated by kit ligand (KL). However, it appears that neither of these cytokines contributes to differentiation of pro-B cells or initiation of expression of Ig gene products. We previously demonstrated that differentiation of pro-B cells and expression of mu-heavy chain is stimulated by either bone marrow stromal cell line S17 or cell free supernatants from that line. This biological activity was attributed to molecules with an apparent M(r) of less than 10 Kd and approximately 40 to 60 Kd. We now report that this biological activity resides with stromal cell-derived insulin-like growth factor-I (IGF-I). Recombinant IGF-I stimulated the expression of cytoplasmic mu-heavy chain in short-term bone marrow cultures and this stimulus was abrogated in the presence of anti-IGF-I antibody. We also demonstrate that either anti-IGF-I antibody or pretreatment of S17 cells with antisense oligonucleotide for IGF-I abrogated the pro-B cell differentiation activity of S17 stromal cell supernatants. Although IGF-I did not directly stimulate proliferation of B-lineage cells, like KL, it potentiated the proliferative stimulus provided by IL-7. Taken together, these data strongly suggest that IGF-I produced by bone marrow stromal cells in the hematopoietic microenvironment plays a key role in regulating primary B lymphopoiesis. PMID- 1515640 TI - Quantification of a novel dense granule protein (granulophysin) in platelets of patients with dense granule storage pool deficiency. AB - An antigen-capture sandwich enzyme-linked immunosorbent assay (ELISA) was developed for a novel protein granulophysin, a constituent of the platelet dense granule (DG) membrane and used to characterize patients with dense granule storage pool deficiency (delta-SPD). The assay uses two monoclonal antibodies against the protein, one of which is conjugated to peroxidase. Purified DGs, an enriched source of the protein, were used for the standard curve. Granulophysin levels were only low in forms of delta-SPD associated with albinism. Granulophysin levels in platelet homogenates of 30 patients with the Hermansky Pudlak syndrome form of delta-SPD were 1/4 to 1/5 of levels in controls or obligate heterozygotes. Two patients with the Chediak-Higashi form of delta-SPD syndrome also had markedly reduced levels of granulophysin. Patients with other forms of delta-SPD had normal levels of granulophysin. Two sisters with delta-SPD in one family had normal granulophysin present in empty dense granule membrane vesicles. Three members of another family with delta-SPD had low DG counts but normal granulophysin levels, indicating that in this group the level of granulophysin was maintained despite the reduction in granule formation. Thus, granulophysin quantitation facilitates characterization of delta-SPD patients and may provide clues to the nature of defective granules in delta-SPD subtypes. PMID- 1515641 TI - Antithrombotic properties of L-cysteine, N-(mercaptoacetyl)-D-Tyr-Arg-Gly-Asp sulfoxide (G4120) in a hamster platelet-rich femoral vein thrombosis model. AB - Platelet aggregation plays an important role in the pathogenesis in arterial thrombotic disorders. The binding of fibrinogen via the Arg-Gly-Asp (RGD) recognition sequence to the platelet glycoprotein IIb/IIIa (GPIIb/IIIa) receptor is an essential step of platelet aggregation induced by various physiologic agonists, and RGD-containing peptides that bind to the GPIIb/IIIa receptor inhibit thrombus formation in vivo. L-cysteine, N-(mercaptoacetyl)D-tyrosyl-L arginylglycyl-L alpha-aspartyl-cyclic (1----5)-sulfide, 5-oxide (G4120), a cyclic RGD-containing synthetic pentapeptide, inhibits adenosine diphosphate (ADP) induced platelet aggregation with 50% inhibition (IC50) at a concentration of 0.05 microgram/mL in human plasma, 0.12 microgram/mL in hamster plasma, and 11 micrograms/mL in rat plasma. Corresponding values for the linear tetrapeptide Arg Gly-Asp-Phe (RGDF) were 7 and 100 micrograms/mL in human and hamster plasma. The antithrombotic effects of G4120 and RGDF were evaluated in a hamster model consisting of a mural platelet-rich femoral vein thrombus induced by standardized endothelial cell damage. Bolus intravenous injection of G4120 was followed by a biphasic disappearance of G4120 from plasma with t1/2 alpha of 3.7 minutes and t1/2 beta of 63 minutes, corresponding to a plasma clearance of 5.2 +/- 0.68 mL/min. Bolus intravenous injection of G4120 inhibited ex vivo platelet aggregation with 0.5 mumol/L ADP and in vivo thrombus formation in a dose dependent manner, with ID50 of 11 and 11 micrograms/kg, respectively. Bolus injection of RGDF inhibited in vivo thrombus formation; 43% inhibition was obtained at a dose of 30 mg/kg. Thus, this hamster platelet-rich femoral vein thrombosis model may be useful for the investigation of the antithrombotic properties of platelet GPIIb/IIIa antagonistic peptides. The cyclic synthetic peptide G4120 appears to have a very potent antithrombotic activity in vivo. PMID- 1515642 TI - Atypical Wiskott-Aldrich syndrome in a girl. AB - Wiskott-Aldrich syndrome (WAS) is a fully penetrant X-linked recessive disorder characterized by thrombocytopenia with small platelets, eczema, and defects of both T-cell and B-cell immunity. Obligate carriers of this disorder show no signs of the gene defect because in the cell lineages primarily affected by the disorder they demonstrate preferential use of the normal, nonmutant X as the active X. This can be explained by the selective disadvantage in proliferation and/or survival experienced by the cells with the mutant X as the active X. We have recently evaluated an 8-year-old girl with a disorder phenotypically identical to WAS. Cytogenetic studies did not show any structural abnormalities of the X chromosome and X chromosome inactivation analysis showed that both of her X chromosomes could function as the active X. These findings suggest that there is an autosomal recessive disorder that is very similar to classic WAS. PMID- 1515643 TI - Growth and spread of human malignant T lymphoblasts in immunosuppressed nude mice: a model for meningeal leukemia. AB - Previous work has shown that nude (nu/nu) mice additionally immunosuppressed by splenectomy, sublethal irradiation, and treatment with antiasialo GM1 antiserum (SIA-nu/nu mice) have no detectable natural killer activity and allow the growth of human malignant lymphoblasts. We show here that all SIA-nu/nu mice engrafted intravenously with 5 x 10(6) malignant lymphoblasts originally derived from a child with a T-cell acute lymphoblastic leukemia (PF382) and from a boy with a T cell lymphoma (ST-4) develop lethal meningeal leukemia and die within 35 days. Histologic examination of moribund SIA-nu/nu mice showed that vertebral and skull bone marrow was always replaced by proliferating human T lymphoblasts. From the spinal canal, lymphoblasts spread to the meninges, causing hind leg paralysis. Leaving the skull, they permeated the meninges and then invaded the nervous parenchyma. This efficient and reproducible experimental model may be suitable for experimental studies on the pathogenesis of meningeal leukemia. PMID- 1515644 TI - Follicular dendritic cells inhibit human B-lymphocyte proliferation. AB - In germinal centers, B lymphocytes are intimately associated with follicular dendritic cells (FDCs). It has been hypothesized that FDCs are involved in the regulation of B-cell growth and differentiation through cell-cell interactions. In this study, highly enriched preparations of FDCs were isolated by cell sorting using the FDC restricted monoclonal antibody DRC-1. When irradiated FDCs were cultured with mitogen stimulated B cells, B cell 3H-TdR uptake was inhibited by up to 80%. This inhibitory effect was not seen when paraformaldehyde fixed FDCs were added to B-cell cultures, suggesting that the FDCs needed to be metabolically active. Moreover, supernatants from cultured FDCs were similarly able to inhibit B-cell proliferation. These results demonstrate that FDCs may downregulate the clonal expansion of B cells that occurs within lymphoid follicles as part of the normal physiologic immune response. Potentially, the loss of the inhibitory role of FDCs in vivo may be of importance in certain infectious and neoplastic processes in which germinal centers are affected. PMID- 1515645 TI - Sensitivity of fresh acute myeloid leukemia cells to etoposide: relationship with cell growth characteristics and DNA single-strand breaks. AB - In this study, we evaluated the individual in vitro sensitivity of fresh acute myeloid leukemia (AML) cells to VP-16, and attempted to correlate VP-16 cytotoxicity with AML cell growth characteristics and drug-induced DNA single strand breaks (SSB). Primary (PE1) colony inhibition assays allowed us to characterize two distinct groups of AML: group I (patients 1 through 6), which displayed sensitivity to VP-16 similar to that of normal CFU-GM (IC90 of 20.52 +/ 2.44 micrograms/mL v 20.48 +/- 2.23 micrograms/mL after 1 hour drug exposure, respectively); and group II (patients 7 through 11), which was more sensitive to VP-16 (IC90 of 7.26 +/- 2.93 micrograms/mL, P = .004). Subsequently, groups I and II were termed normosensitive and hypersensitive, respectively. This objective VP 16 sensitivity classification, as determined by PE1, remained unaltered when assessed by secondary (PE2) colony inhibition assay (evaluating the self-renewal fraction of AML progenitors), or by cytofluorometric viability assay (evaluating the ultimately differentiated blast cell population). These findings would suggest that individual sensitivity to VP-16 of a particular cell population is maintained throughout CFU-AML differentiation. Finally, we report that sensitivity of AML cells to VP-16 did not correlate either with cell growth characteristics or with SSB generation. Indeed, AML cell sensitivity to VP-16 appeared more closely related to DNA repair kinetics after drug removal, ie, hypersensitivity being essentially characterized by a prolonged retention of SSB during the posttreatment period. Interestingly, the established HL-60 cell line, which presented greater sensitivity to VP-16 cytotoxicity than KG1, HEL, and K562, was also found to exhibit delayed DNA SSB repair kinetics, as compared with the other AML cell lines. These results suggest that hypersensitivity to VP-16 of some AML cells may be related to a deficient DNA-repair mechanism. PMID- 1515647 TI - Delta-thalassemia caused by disruption of the site for an erythroid-specific transcription factor, GATA-1, in the delta-globin gene promoter. AB - Delta-thalassemia is a complex group of inherited disorders of globin genes characterized by impaired synthesis of the delta-globin chain. The T-C substitution was detected at position -77 of the delta-globin gene isolated from three independent Japanese individuals who were homozygotes for delta thalassemia. To elucidate the significance of the mutation in delta-globin gene expression, we investigated the genotype of three delta-thalassemia homozygotes and 58 normal individuals using dot blot hybridization of the polymerase chain reaction (PCR)-amplified DNA. The mutation was observed in six alleles of three homozygotes, while no mutation was detected in 116 alleles of normal individuals, thereby indicating the close association of this mutation with the thalassemia phenotype. Since the mutation (TTATCT-TCATCT) is located within the inverted binding motif of GATA-1 (T or A-G-A-T-A-G or A), an erythroid cell-specific transcription factor, we did gel retardation assays using nuclear extracts from the erythroid cells. We found that GATA-1 binds the oligonucleotide spanning positions -61 to -90, but does not bind to the oligonucleotide with the mutation at position -77. Competition gel retardation assays showed that GATA-1 binding can be competed out by the fragment with the GATA-1 motif, but not with the mutant oligonucleotide. Analysis of the transient expression of the CAT gene linked to the delta-globin gene promoter region demonstrated that the construct with the mutant promoter region was expressed about 20-fold less compared with the normal one. Thus, the mutation at position -77 impairs delta-globin gene expression by abolishing GATA-1 binding to the AGATAA sequence of the promoter region of the delta-globin gene. This provides a good example of involvement of tissue-specific transacting factors in the molecular pathogenesis of hereditary diseases. PMID- 1515646 TI - Effect of herbimycin A, an antagonist of tyrosine kinase, on bcr/abl oncoprotein associated cell proliferations: abrogative effect on the transformation of murine hematopoietic cells by transfection of a retroviral vector expressing oncoprotein P210bcr/abl and preferential inhibition on Ph1-positive leukemia cell growth. AB - Herbimycin A, a benzoquinoid ansamycin antibiotic, was demonstrated to decrease intracellular phosphorylation by protein tyrosine kinase (PTK). In Philadelphia chromosome (Ph1)-positive leukemias such as chronic myelogenous leukemia (CML) and Ph1-positive acute lymphoblastic leukemia (ALL), both of which express bcr abl fused gene products (P210bcr-abl or P190bcr-abl protein kinase) with augmented tyrosine kinase activities, herbimycin A markedly inhibited the in vitro growth of the Ph1-positive ALL cells and the leukemic cells derived from CML blast crisis. However, the same dose of herbimycin A did not inhibit in vitro growth of a broad spectrum of Ph1-negative human leukemia cells, and several other protein kinase antagonists also displayed no preferential inhibition. Furthermore, we demonstrated that herbimycin A has an antagonizing effect on the growth of transformed cells by a transfection of retroviral amphotrophic vector expressing P210bcr/abl into a murine interleukin (IL)-3-dependent myeloid FDC-P2 cell line. This inhibition was abrogated by the addition of sulfhydryl compounds, similar to the reaction previously described for Rous sarcoma virus transformation. The inhibitory effect of herbimycin A on the growth of Ph1 positive cells was associated with decreased bcr/abl tyrosine kinase activity, but no decrease of bcr-abl mRNA and protein, suggesting that the inactivation of bcr-abl tyrosine kinase activity by herbimycin A may be induced by its binding to the bcr-abl protein portion that is rich with sulfhydryl groups. The present study indicates that herbimycin A is a beneficial agent for the investigation of the role of the bcr-abl gene in Ph1-positive leukemias and further suggests that the development of agents inhibiting the bcr-abl gene product may offer a new therapeutic potential for Ph1-positive leukemias. PMID- 1515648 TI - Treatment of chronic myeloid leukemia with allogeneic bone marrow transplantation after preparation with BuCy2. AB - One hundred fifteen patients with chronic myelocytic leukemia (CML) were administered busulphan 4 mg/kg for 4 days and cyclophosphamide 60 mg/kg on each of 2 days (BuCy2) followed by allogeneic bone marrow transplantation from histocompatible sibling donors. For 62 patients in chronic phase, 26 in accelerated phase, and 27 in blast transformation, the actuarial survival at 3 years was 58%, 41%, and 25%, respectively. Actuarial probability of relapse was 3%, 12%, and 27%, respectively. Only two patients in chronic phase showed a transient cytogenetic relapse and one of these died from subsequent transplant related complications, whereas the other remains cytogenetically normal 697 days posttransplant. Patients who were transplanted within 1 year of diagnosis in chronic phase had a survival of 70% compared with 40% when transplanted beyond 1 year from diagnosis. This significant difference in survival was due to transplant-related complications and was correlated with previous exposure to high doses of busulphan. This study indicates that BuCy2 is a useful conditioning regimen for marrow transplantation in patients with CML and results in similar survival statistics and transplant-related mortality as would be expected with conditioning regimens containing total body irradiation. It is possible that relapse after BuCy2 may be lower than expected with regimens containing total body irradiation, but larger analyses are required. PMID- 1515649 TI - The T----C substitution at nucleotide + 1570 of the beta-globin gene is a polymorphism. PMID- 1515650 TI - Acute lymphoblastic leukemia: hypofibrinogenemia with a low incidence of clinical complications is often found during induction remission therapy. PMID- 1515651 TI - Acute myeloid leukemia with T-lymphoid expression and distinct chromosomal abnormalities. PMID- 1515652 TI - Human breast cancer: survival from first metastasis. Breast Cancer Study Group. AB - Survival from the detection of first metastasis (SAM) was analyzed in a single center series of 258 patients with advanced breast cancer. During the 15 year period covered by this study 230 patients died, 215 of their disease. The overall median SAM was 28 months. Univariate analysis of SAM stratified by first dominant site of metastasis, estrogen receptor status (ER), progesterone receptor status (PgR), tumor size, axillary lymph node status, patient age, menopausal status, and disease-free interval (DFI) showed the first dominant site of metastasis, ER, PgR, and axillary lymph node status to be significantly associated with SAM. Patients with visceral metastasis as first dominant site of metastasis had significantly shorter survival than those with either bone or soft tissue metastasis, median SAM 16 vs. 34 vs. 41 months respectively (P less than 0.001). SAM also differed according to the steroid hormone receptor status of the primary tumor: median SAM 34 and 33 months for patients with ER-positive or patients with PgR-positive tumors against 14 months for patients with ER-negative or with PgR negative tumors (P less than 0.001). Patients with axillary lymph node involvement at primary disease had a shorter SAM than those without, median SAM 24 vs. 35 months (P = 0.006). No association between SAM and either tumor size, patient age, menopausal status, or DFI could be observed. Multivariate analysis including first dominant site of metastasis, ER, PgR, and axillary lymph node status showed the first dominant site of metastasis, ER, and axillary lymph node status to be independently associated with SAM. PMID- 1515653 TI - Prognostic significance of the immunohistochemical reaction to human milk fat globule antibodies in node-negative and node-positive breast cancer. AB - The status of axillary lymph nodes in patients with breast cancer is important prognostically but does not identify all patients who will have long or short survival. To determine if the immunohistochemical reaction of tumor cells to human milk fat globule (HMFG) antibodies will define prognosis more specifically, we examined patients with node-negative disease and patients with more than three positive nodes, the extremes of the prognostic spectrum. In both node-negative and node-positive groups, patients who relapsed were matched by age at diagnosis, tumor size, histologic type, and receptor status, with patients who remained disease-free for a minimum of 48 months. Patients with poor survival had a higher proportion of poorly differentiated cancers. The ability to generate antigens recognized by HMFG antibodies was decreased in patients with recurrent disease, but this was significant only in patients with node-positive tumors. Tumors of patients who remained disease-free were more likely to have a pattern of membrane staining, while cytoplasmic staining was more frequent in those who relapsed. The results suggest that immunohistologic response to HMFG antibodies may assist in identifying cancers with poor prognosis, supplementing the prediction derived from node status. PMID- 1515655 TI - Exclusion of residual angiosarcoma of the breast by MRI. PMID- 1515654 TI - Epithelial membrane antigen expression in breast fluids and 'witch's milk'. AB - We have examined breast fluids from non-lactating women and male neonates for the expression of epithelial membrane antigen (EMA), also termed polymorphic epithelial mucin (PEM). All fluids exhibited significant amounts of EMA as demonstrated by immunoblot analyses and enzyme immunoassay. EMA was present in the breast fluids of both pre- and post-menopausal women, and these results suggest that nipple aspirates could provide an easily accessible source of antigen for assessing the value of EMA as a tumor marker both before and after various therapeutic modalities. The presence of EMA in the 'witch's milks' indicates that full maturation of the breast is not a prerequisite for antigen expression in breast tissue. PMID- 1515656 TI - The value of clinical assessment in the diagnosis of icterus and cholestasis. AB - We studied the reliability of the clinical assessment and the discriminatory value of different symptoms and signs in diagnosing obstructive and non obstructive diseases causing icterus and/or cholestasis. During a period of two and-a-half years, clinical assessment done by both physicians-in-training and by senior physicians was completed for 266 patients, and the usefulness of different symptoms and signs was tested in 220 of these. Clinical assessment was found to be a reliable method in distinguishing between obstructive and non-obstructive conditions causing icterus, with the sensitivity of 92% and specificity of 86%. In cases of anicteric cholestasis, the sensitivity and specificity of clinical assessment were 74% and 80%, respectively. Abdominal pain and abdominal tenderness were significantly (p less than 0.01) associated with obstructive diseases, whereas an enlarged liver, fever and excessive consumption of alcohol were associated with non-obstructive diseases (p less than 0.01, p less than 0.05, p less than 0.05, respectively). Itching, vomiting, intolerance to fatty foods, previous cholecystectomy, abdominal tumour and clinical icterus had no discriminatory value. Clinical evaluation is a reliable method in the diagnostic workup of a patient with icterus or anicteric cholestasis, and it is still of crucial importance in directing further investigations. PMID- 1515657 TI - Endoscopy to detect oral and oesophageal candidiasis in acquired immune deficiency syndrome. AB - Cytologic evidence of candidiasis was sought on endoscopic oesophageal brushings from 116 patients with acquired immune deficiency syndrome (AIDS) to determine the reliability of oesophagoscopy and the possibility of predicting Candida spp. oesophagitis from concomitant oral candidiasis or oesophageal symptoms. Oesophageal candidiasis was present in 42 patients and constituted the first opportunistic infection in 19 patients. Sensitivity and specificity were, respectively, 98% and 96% for oesophagoscopy, 69% and 42% for oral candidiasis, 52% and 74% for oesophageal symptoms, and 83% and 35% for the presence of at least one of these last two parameters. Endoscopy also proved to be the examination of choice for diagnosis, and cytology was needed only when it was negative. Oral candidiasis and oesophageal symptoms were not sufficient to predict oesophageal candidiasis. Endoscopy would seem to be indispensable to the diagnosis of oesophageal candidiasis and its differentiation from other forms, thus preventing any empirical resort to unwarranted forms of treatment. It is also indicated for staging purposes in asymptomatic patients, since oesophageal candidiasis is one indicator of the transition to full-blown AIDS. PMID- 1515658 TI - Androgen profile in patients with pancreatic carcinoma. AB - Serum testosterone, free testosterone and androstenedione levels were measured in 28 male patients with pancreatic cancer and compared with the values obtained from 28 male patients with chronic pancreatitis, 29 with gastrointestinal malignancies and 41 healthy controls. Mean total testosterone values were significantly lower in the pancreatic cancer group when compared to chronic pancreatitis and healthy controls. Total testosterone concentrations were also significantly lower in patients with gastrointestinal malignancies when compared to healthy controls. No difference was found in free testosterone and androstenedione levels in the four groups of patients. Total testosterone serum levels correlated significantly with poor nutritional status. This study confirms low testosterone levels in patients with pancreatic cancer, but provides no evidence to support a direct relationship between pancreatic cancer and testosterone metabolism. PMID- 1515659 TI - The theophylline disposition after caffeine administration in liver cirrhosis: an index of liver function. AB - Six blood samples covering a 24 hr post caffeine dosage were drawn in 8 healthy subjects and 18 patients with liver cirrhosis. Caffeine and theophylline concentration were assayed by gas-chromatography and fluorescent polarization immunoassay, respectively. In normals the maximum theophylline levels were found between 3 and 8 hrs (62.5% at 8 hrs) and ranged 50-420 ng/ml, whereas these levels in cirrhotic patients were noted between 3 and 12 hrs (61.1% at 8 hrs) and ranged 40-670 ng/ml. The largest difference in mean theophylline concentration between normals and cirrhotics was found at 6 hrs (348 +/- 103.7 ng/ml vs 217.1 +/- 140.8 ng/ml; p less than 0.02) and 24 hrs (101.6 +/- 57.3 ng/ml vs 172.2 +/- 119.6 ng/ml; p = 0.075) after caffeine dosing. Theophylline formation rate (theo6) differentiated controls from cirrhotics in the initial stage of the disease (Child-Pugh A), however it failed to discriminate between initial and late cirrhosis. In contrast, the ability of liver to remove theophylline (theo24) differentiated effectively these groups of patients. Theo6 to theo24 ratio was a valuable index of liver function, although its capacity to detect early cirrhosis was unsatisfactory. PMID- 1515660 TI - Treatment of erosive reflux oesophagitis: a double-blind multicentre trial with nizatidine 300 mg b.i.d. versus placebo. AB - Histamine H2-receptor antagonists at conventional doses have proved only partly efficacious in the treatment of reflux oesophagitis. The aim of this study, therefore, was to compare the efficacy of high doses of nizatidine (300 mg b.i.d.) versus placebo in 117 patients with grade I and II oesophagitis. After 6 weeks' treatment, 70.6% of nizatidine-treated patients showed complete endoscopic healing against 25.4% of placebo-treated subjects (p less than 0.001). After 12 weeks, the respective healing rates were 77.5% and 47.4% (p less than 0.01). Nizatidine also proved significantly more effective than placebo in improving overall symptoms (p less than 0.05). Antacid intake was significantly greater in the placebo group (p less than 0.001). Both treatments were well tolerated. In conclusion, this study demonstrates that nizatidine at the dose of 300 mg b.i.d. for 6-12 weeks constitutes an effective treatment for patients with reflux oesophagitis. PMID- 1515661 TI - The prevalence of gallstones in patients suffering from liver cirrhosis: a clinico-statistical study of 350 patients. AB - The overall prevalence according to sex and to age group of biliary calculosis was assessed in 350 patients with liver cirrhosis: data were compared with homogeneous findings in the general population of the GREPCO study. Cholelithiasis was found to be significantly more frequent in cirrhotics, and the pattern was confirmed when data were analyzed according to sex; a significantly higher percentage was found in cirrhotics of the 40-49 and 60-69 age groups. Among cirrhotics with gallstones, alcoholics represented a smaller percentage compared to non-lithiasic cirrhotics. The incidence of complications such as digestive hemorrhage, coma, and hepato-renal syndrome, was equal in cirrhotics with and without biliary calculosis, or, as far as coma was concerned, even lower among the former. A fatal outcome was less frequent in cirrhotic patients with than in those without cholelithiasis. Our results go to show that biliary calculosis does not aggravate the course of liver cirrhosis. PMID- 1515662 TI - Neurotensin: a physiological regulator of exocrine pancreatic secretion? AB - The aim of the present review was to evaluate the effects of neurotensin on the exocrine pancreatic secretion. Neurotensin immunoreactivity has been identified in the central nervous system and also in the digestive system, where it is found in specific endocrine cells of the intestinal mucosa (N cells), in nerve fibers of the enteric nervous system and in intrapancreatic ganglia (both in nerves and cell bodies). Studies in laboratory animals and in humans have demonstrated that the ingestion of a meal causes a significant release of neurotensin into the circulation and that exogenous administration of low doses of the peptide strongly stimulates exocrine pancreatic secretion. These findings, together with the demonstration that the immunoneutralization of circulating neurotensin significantly reduces the pancreatic secretory response to a meal, suggest that neurotensin is a physiological regulator of exocrine pancreatic secretion. PMID- 1515663 TI - Subclinical coeliac disease. AB - The prevalence of coeliac disease (CD) was investigated in an epidemiological study of school children from a district of Rome. Mass screening of IgA-AGA levels (anti-gliadin antibody) were determined in blood samples from the study group and the results were positive in 19 children. Eighteen of these agreed to undergo endoscopic biopsy. Histological study of the duodenal specimens revealed villous atrophy in twelve children none of whom had the characteristic symptoms of CD. The most frequent complaints were abdominal pain, aphtous stomatitis, and atopic dermatitis. The high prevalence of CD in this study suggests the necessity for the widest range of epidemiological research. PMID- 1515664 TI - Evolution of agrobacteria and their Ti plasmids--a review. PMID- 1515665 TI - Regulation of enzymes involved in lignin biosynthesis: induction of O methyltransferase mRNAs during the hypersensitive reaction of tobacco to tobacco mosaic virus. AB - The mRNAs encoding orthodiphenol-O-methyltransferases (OMTs; EC 2.1.1.6), which are involved in the biosynthesis of lignin precursors, are highly induced in tobacco leaves during the hypersensitive reaction to tobacco mosaic virus (TMV). OMT messengers were fractionated on a sucrose gradient and translated in vitro. Protein A-Sepharose columns adsorbed with specific antisera raised against purified OMTs were used to select translation products, and the translatable activity of OMT mRNA was measured at different stages of infection. Oligonucleotides derived from peptide sequences of purified OMT I were used to prime polymerase chain reactions; total RNA was used as template to allow the isolation of an OMT I clone. RNA blots, hybridized with the OMT I probe, revealed a unique messenger of 1.7 kb. The kinetics of accumulation of OMT I mRNAs during the hypersensitive reaction to TMV parallels the kinetics of translation and suggests that an increase in mRNA controls the increase in the rate of enzyme synthesis. In healthy plants, RNA blot hybridization showed that the steady-state level of OMT I mRNA is very high in vascular tissue compared to the level measured in leaves. PMID- 1515666 TI - Analysis of DNA sequences transcribed at high levels in Bradyrhizobium japonicum bacteroids but not necessary for symbiotic effectiveness. AB - Five regions of the Bradyrhizobium japonicum genome, which are transcribed at high levels in nitrogen-fixing soybean (Glycine max) nodules, were identified. None of these regions contained previously identified genes (e.g., nif, nod, and fix genes) that are known to be essential for development of functional nitrogen fixing nodules. To assess the role of these regions in the development of the B. japonicum-soybean symbiosis, we cloned and used them to construct B. japonicum strains, in which large DNA segments (2.0-6.8 kilobases) containing the highly transcribed regions were deleted. The deletion strains were examined for symbiotic effectiveness and were found to be indistinguishable from the wild-type strain. Transcription of the cloned regions under a variety of physiological conditions and in several defined mutant B. japonicum strains was also examined. The transcriptional start sites for one pair of divergent transcripts were determined; the promoters do not contain any of the conserved sequences found in B. japonicum genes involved in symbiosis or nitrogen metabolism. PMID- 1515667 TI - Expression of a viral avirulence gene in transgenic plants is sufficient to induce the hypersensitive defense reaction. AB - Tobacco plants containing the N' resistance gene exhibit a hypersensitive defense reaction when infected with tomato mosaic virus (ToMV); infection results in necrotic lesions at the primary infection sites. In an attempt to investigate the molecular mechanism(s) underlying this plant-pathogen interaction, the ToMV coat protein gene was joined by a transcriptional fusion to the strong constitutive 35S RNA promoter from cauliflower mosaic virus. This chimeric gene was introduced via Agrobacterium-mediated transformation into isogenic tobacco cultivars differing only with respect to the N' gene. Strong necrotic reactions were observed on most emerging calli of the N' genotype, but never on calli lacking the N' resistance gene. These data indicate that the coat protein of ToMV is, on its own, sufficient to induce a hypersensitive reaction in tobacco. Thus, recognition of a single viral gene product may be the only prerequisite for the induction of a specific defense reaction in higher plants. PMID- 1515668 TI - Identification of a lysA-like gene required for tabtoxin biosynthesis and pathogenicity in Pseudomonas syringae pv. tabaci strain PTBR2.024. AB - Pseudomonas syringae pv. tabaci strain PTBR2.024 produces tabtoxin and causes wildfire disease on tobacco and green bean. PTBR7.000, a Tn5 mutant of PTBR2.024, does not produce tabtoxin, is nonpathogenic on tobacco, and is prototrophic. A 3 kb fragment from a genomic library of the parent strain PTBR2.024 complemented both mutant phenotypes. This 3-kb fragment contains two open reading frames (ORFs), ORF1 and ORF2, and two truncated ORFs, ORF3 and ORF4. The Tn5 insert in PTBR7.000 was mapped to ORF2, and complementation studies showed that an intact ORF2 was sufficient to restore tabtoxin production and pathogenicity. The deduced amino acid sequences of ORF2 and truncated ORF3 contain significant homology to bacterial lysine biosynthetic enzymes, diaminopimelate decarboxylase, and delta 1 piperidine-2,6-dicarboxylate succinyl transferase, respectively. ORF2, however, is not required for lysine biosynthesis. We designated the sequence corresponding to ORF2 as gene tabA and propose that the product of tabA is an enzyme in the tabtoxin biosynthetic pathway that recognizes a substrate analogue of a compound in the lysine biosynthetic pathway. PMID- 1515669 TI - The a and b loci of Ustilago maydis hybridize with DNA sequences from other smut fungi. AB - The smut fungi are obligately parasitic during the sexual phase of their life cycle, and the mating-type genes of these fungi play key roles in both sexual development and pathogenicity. Among species of smut fungi it is common to find a bipolar mating system in which one locus with two alternate alleles is believed to control cell fusion and establishment of the infectious cell type. Alternatively, several species have a tetrapolar mating system in which two different genetic loci, one of which has multiple alleles, control fusion and subsequent development of the infection hyphae. Cloned sequences from the a and b mating-type loci of the tetrapolar smut fungus Ustilago maydis were used as hybridization probes to DNAs from 23 different fungal strains, including smut fungi with both tetrapolar and bipolar mating systems. In general, all of the smut fungi hybridized with the mating-type genes from U. maydis, suggesting conservation of the sequences involved in mating interactions. A selection of DNAs from other ascomycete and basidiomycete fungi failed to hybridize with the U. maydis mating-type sequences. Exceptions to this finding include hybridization of DNA from the a1 idiomorph of U. maydis to DNA from one strain of U. violacea and hybridization of both a idiomorphs to DNA from Saccharomyces cerevisiae. PMID- 1515670 TI - Morphology of the adrenal homologues in two hillstream teleostean fishes from India. AB - In Garra gotyla and Pseudecheneis sulcatus, the interrenal and chromaffin tissues represent homologues of the adrenal cortex and medulla, respectively, and are confined to the largely lymphoid head kidneys in a bilaterally symmetrical topographical pattern. Together they form a collar round the postcardinal vein, with a thickness of 300 microns in Garra gotyla and 150 microns in Pseudecheneis sulcatus. Distributionally, the interrenal tissue conforms to Nandi's type III and type I and the chromaffin tissue to type V and type III in Garra gotyla and Pseudecheneis sulcatus, respectively. The interrenal cells in these species are polygonal, cuboidal or columnar, and are filled with coarse basophilic cytoplasm. The chromaffin cells form syncytial patches and have sparsely granular cytoplasm. PMID- 1515671 TI - A new explanation of the cancellous bone architecture. AB - Various objections can be made to all the theories so far put forward in explanation of the architecture of cancellous bone. The author suggests another explanation, which takes into account the following points: 1) the structure of the secondary spongiosa is based on the pre-existent primary spongiosa, 2) the secondary spongiosa develops under alternating pressures from different directions, 3) oblique forces from marginal directions corresponding to extreme positions on the joint place the greatest strain on the spongiosa trabeculae, as demonstrated by means of a geometrical model. Oblique forces are therefore of decisive morphogenetic importance. 4) The spongiosa trabeculae are oriented in the direction of the oblique marginal forces, in accordance with the experimentally demonstrated mechanism of the strain-dependent reaction of the bone. Spatially, the secondary spongiosa assumes a fan-shaped structure. Two dimensionally, the two intersecting systems are compression systems, each of which depends on another marginal loading direction. This pattern offers an optimum solution to the problem of the transmission of alternating forces to the diaphysis from various directions, using a minimum of material. PMID- 1515672 TI - Origin of the v. portae and variability of its tributaries in laboratory animals. VI. The laboratory mouse (Mus musculus var. alba). AB - The authors studied the origin and variability of the tributaries of the v. portae in 30 adult laboratory mice (Mus musculus var. alba) of both sexes, after first injecting the portal bed with bluedyed latex. In 19 cases (63.3%) the v. portae was formed by the union of three tributaries and in 11 cases (36.7%) by the union of four to eight. The v. mesenterica cranialis was a constant tributary in every case (100%). The v. lieanalis was a tributary in 27 cases (90.0%) and the next most frequent tributary was the v. pancreaticoduodenalis (14 cases- 46.7%) A v. gastrica sinistra was found in every case (100.0%), in 24 cases (80.0%) it joined the v. lienalis and in the other six (20.0%) it was a direct tributary of the v. portae. A v. cardiaca was also observed in every case (100%). In 28 cases (93.3%) it was a tributary of the v. gastrica sinistra and in the remaining two (6.7%) it was a direct tributary of the v. portae. A v. pylorica was found in 27 mice (90.0%). Most often it was a tributary of the v. gastroepiploica dextra (11 cases--36.7%) or the v. gastrica sinistra (9 cases- 30.0%). In only one case was it a direct tributary of the v. portae. A v. pancreaticoduodenalis cranialis was present in a total of 28 cases (93.3%). In 12 cases (40.0%) of already originated in the region of the cauda pancreatis and in 16 cases (53.3%) it arose only from the corpus and caput pancreatis.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1515673 TI - The effect of methotrexate (MTX) on the small intestine of the mouse. III. Mitochondria and succinic dehydrogenase (SDH). AB - The effect of the cytotoxic agent MTX on the mitochondrial content and on SDH activity in the jejunal mucosa of mice was studied. The control epithelium contained variable quantities of mitochondria, in the form of granules, short rods and filaments. In the crypt cells these organelles were larger than in the villus cells. The concentration of mitochondria close to the brush border and the basement membrane is indicative of their importance in production of the energy needed for active transport across the plasma membrane. After MTX treatment, there was a general decrease in the number, size and stainability of the mitochondria. In the control, SDH activity was moderate and its localization coincided topographically with the distribution of the mitochondria. The decrease in SDH activity after MTX, correlated to the decrease in the mitochondrial content, might be due to mitochondrial damage resulting form the indirect effect of MTX. PMID- 1515674 TI - Ultrastructure of rabbit tracheal epithelium after the administration of Hexabrix -a hexaiodated contrast agent for tracheobronchography. AB - The ultrastructure of the tracheal epithelium after the application of 1 ml of Hexabrix (a hexaiodated contrast agent for tracheobronchography) into the airways was studied. Severely altered pseudostratified columnar epithelium was found in the trachea. Eighty-one +/- 5% of the goblet cells had been stimulated to discharged mucus. Forty-three +/- 3% of them were completely exhausted and had degenerated. The ciliated cells displayed marked signs of pathological alteration up to vacuolar degeneration. The ciliary border above the epithelium was severely damaged. The mean number of cilia per micron 2 fell to 3.3 +/- 0.5, but the proportion of intact cilia did not drop below 95%. As morphological signs of impaired self-cleaning ability of the airway epithelium, a large amount of inspissated mucus and numerous bacteria were found in the area of the impaired ciliary border. Coarse grained contrast substance of supreme electron density was intermingled with the condensed mucus. The most pronounced damage to the cells was observed at the sites of direct contact of the contrast agent with the cell membranes. PMID- 1515675 TI - A gene encoding a protein with seven zinc finger domains acts on the sexual differentiation pathways of Schizosaccharomyces pombe. AB - Byr3 was selected as a multicopy suppressor of the sporulation defects of diploid Schizosaccharomyces pombe cells that lack ras1. Like cells mutant at byr1 and byr2, two genes that encode putative protein kinases and that in multiple copies are also suppressors of the sporulation defects of ras1 null diploid cells, cells mutant at byr3 are viable but defective in conjugation. Nucleic acid sequence indicates byr3 has the capacity to encode a protein with seven zinc finger binding domains, similar in structure to the cellular nucleic acid binding protein (CNBP), a human protein that was identified on the basis of its ability to bind DNA. Expression of CNBP in yeast can partially suppress conjugation defects of cells lacking byr3. PMID- 1515676 TI - In vivo import of firefly luciferase into the glycosomes of Trypanosoma brucei and mutational analysis of the C-terminal targeting signal. AB - The compartmentalization of glycolytic enzymes into specialized organelles, the glycosomes, allows the bloodstream form of Trypanosoma brucei to rely solely on glycolysis for its energy production. The biogenesis of glycosomes in these parasites has been studied intensively as a potential target for chemotherapy. We have adapted the recently developed methods for stable transformation of T. brucei to the in vivo analysis of glycosomal protein import. Firefly luciferase, a peroxisomal protein in the lantern of the insect, was expressed in stable transformants of the procyclic form of T. brucei, where it was found to accumulate inside the glycosomes. Mutational analysis of the peroxisomal targeting signal serine-lysine-leucine (SKL) located at the C-terminus of luciferase showed that replacement of the serine residue (Serine548) with a small neutral amino acid (A, C, G, H, N, P, T) still resulted in an import efficiency of 50-100% of the wild-type luciferase. Lysine549 could be substituted with an amino acid capable of hydrogen bonding (H, M, N, Q, R, S), whereas the C-terminal leucine550 could be replaced with a subset of hydrophobic amino acids (I, M, Y). Thus, a peroxisome-like C-terminal SKL-dependent targeting mechanism may function in T. brucei to import luciferase into the glycosomes. However, a few significant differences exist between the glycosomal targeting signals identified here and the tripeptide sequences that direct proteins to mammalian or yeast peroxisomes. PMID- 1515678 TI - Ethnos and ethos. PMID- 1515679 TI - The language of epidemiology (XIII) Cause. PMID- 1515677 TI - A low copy number central sequence with strict symmetry and unusual chromatin structure in fission yeast centromere. AB - Fission yeast centromeres vary in size but are organized in a similar fashion. Each consists of two distinct domains, namely, the approximately 15-kilobase (kb) central region (cnt+imr), containing chromosome-specific low copy number sequences, and 20- to 100-kb outer surrounding sequences (otr) with highly repetitive motifs common to all centromeres. The central region consists of an inner asymmetric sequence flanked by inverted repeats that exhibit strict identity with each other. Nucleotide changes in the left repeat are always accompanied with the same changes in the right. The chromatin structure of the central region is unusual. A nucleosomal nuclease digestion pattern formed on unstable plasmids but not on stable chromosome. DNase I hypersensitive sites correlate with the location of tRNA genes in the central region. Autonomously replicating sequences are also present in the central region. The behavior of truncated minichromosomes suggested that the central region is essential, but not sufficient, to confer transmission stability. A portion of the outer repetitive region is also required. A larger outer region is necessary to ensure correct meiotic behavior. Fluorescence in situ hybridization identified individual cens. In the interphase, they cluster near the nuclear periphery. The central sequence (cnt+imr) may play a role in positioning individual chromosomes within the nucleus, whereas the outer regions (otr) may interact with each other to form the higher-order complex structure. PMID- 1515680 TI - The physician in aviation. AB - As the human body was introduced to flight and its unfamiliar, hostile atmospheric environment, the medical profession had to become familiar with its effects in order to develop preventive measures. In this way, the field of aerospace medicine had its origin. PMID- 1515681 TI - Motor vehicle fatalities in Rhode Island (FY1990-1991): a report on driver impairment. AB - Autopsy specimens from 52 fatally injured drivers in Rhode Island were analyzed for the presence of alcohol and other drugs of abuse, including, among others, cocaine, opiates, cannabinoids (THC), and phencyclidine (PCP). The ages of the drivers ranged from 16 to 87 years; 41 were male and 11 female. Based on this sample, 65% of Rhode Island driver fatalities involve drugs. The most common drug, alcohol was found in 59% of the cases. Drugs other than alcohol were detected in 19% of the cases, 13% had illicit drugs found in combination with alcohol, and 6% had illicit drugs only. PMID- 1515682 TI - Affordability considerations in certificate-of-need hospital capital expenditure review determinations. AB - Beginning in 1984, public affordability became a central standard along with public need in the review of hospital proposals for capital development in Rhode Island's certificate-of-need (CON) program. PMID- 1515683 TI - Affinity groups: mentoring plus. PMID- 1515684 TI - Medical ethics in an outpatient setting: conflicting cultural values. PMID- 1515685 TI - Evaluation of autonomic function. AB - Clinical laboratory evaluation of adrenergic function is lacking in sensitivity. Recent studies suggest that components of the Valsalva maneuver can be used to evaluate adrenergic function. Late phase II and phase IV are primary regulated by peripheral and cardiac sympathetic activity, respectively. With progressive adrenergic failure there is a loss of IIl, an increase in IIe and a loss of IV in that order. Baroreflex gain can be described by the heart period/blood pressure (BP) response. An alternative approach of expressing latency instead of gain is of interest but is of uncertain validity. Evaluation of heart rate recordings in the frequency domain using power spectral analysis can be used to study parasympathetic/sympathetic balance in humans. Its value as a clinical test remains to be established. Prolonged tilt is a sensitive and probably specific test of vasodepressor syncope. Isoproterenol infusion during tilt is of doubtful specificity. PMID- 1515686 TI - Aging and the autonomic nervous system. AB - Most studies show a decline in autonomic nervous system (ANS) function with advancing age. The occasional heterogenous responses of ANS to aging, however, suggest that psychosocial and physiologic factors alter aging of ANS function. PMID- 1515687 TI - Autonomic involvement in systemic diseases. AB - It is now well recognized that autonomic dysfunction may occur in disorders affecting the various body systems. Over the past year important observations have been reported in congestive cardiac failure, reflex sympathetic dystrophy (RSD), acquired immune deficiency syndrome (AIDS) and diabetes mellitus. PMID- 1515688 TI - Autonomic dysfunction in central nervous system disorders. AB - Dysautonomic symptoms are associated with many disorders of the central nervous system, in some of which the autonomic dysfunction is particularly conspicuous or the major cause of disability. New neuroimaging procedures and microneurographic techniques have helped to clarify the underlying pathophysiology and to distinguish or, classify disorders that are clinically similar. Recent studies also suggest that the autonomic nervous system is involved more frequently or extensively than previously thought in certain neurological conditions such as multiple sclerosis or human immunodeficiency virus (HIV) infection, and have helped to define the nature of its involvement in other disorders. PMID- 1515689 TI - Treatment of autonomic failure. AB - The group of primary autonomic failure (AF) syndromes comprises pure AF (PAF), in which there are no central neurological signs, and multiple system atrophy (MSA) in which AF is accompanied by the overlapping degenerative disorders, striatonigral degeneration and olivopontocerebellar atrophy. Patients with these syndromes deteriorate progressively but, based on an understanding of the precise sites of the lesions, there are several ways of alleviating their deterioration, in particular the most disabling symptom, postural hypotension. The principles can be used in the treatment of AF in other general medical disorders, such as diabetes. PMID- 1515690 TI - 5-HT in nervous system disease and migraine. AB - New developments defining the relationship between 5-hydroxytryptamine (5-HT; serotonin)1B and 5-HT1D receptors are reviewed and a novel pain control system involving spinal 5-HT3 receptors is described. The emerging roles of 5-HT receptor mechanisms in migraine and in the craving for alcohol are discussed. PMID- 1515691 TI - Chemotherapy of gliomas. AB - Gliomas are usually incurable with current treatment regimens. The mainstay of current therapy is surgery and radiotherapy. Adjuvant chemotherapy with nitrosourea-based regimens for high-grade glioma has now been established as a means of improving survival times, although the results are disappointing and the treatment may entail significant morbidity and does not offer the prospect of cure. The role of chemotherapy for low-grade glioma is controversial, and its possible role as a primary therapy aimed at delaying the need for radiotherapy in young children must be better defined. The literature regarding chemotherapy of glioma is reviewed with particular emphasis on recent publications. PMID- 1515692 TI - Neoplastic disease of the spine. AB - Spinal cord tumours continue to be a challenging clinical problem. Early diagnosis, especially with widespread use of magnetic resonance imaging (MRI), and advances in surgical technique enable a more aggressive approach to the management of these lesions. PMID- 1515693 TI - Myelitis and toxic, inflammatory and infectious disorders. AB - Developments in our understanding of the anatomical-clinical and pathological correlates of spinal cord disorders have greatly enhanced our understanding of the clinical presentation. The impact of viral disease on the spinal cord is reviewed. The value of magnetic resonance (MR) scanning of the brain and spinal cord in the evaluation, both in the short and long term, of patients with myelopathy is underlined. PMID- 1515694 TI - Spinal cord injury. AB - Continued investigation of the pathophysiology of primary and secondary neuronal injury following acute spinal cord injury (SCI) has led to positive results in two medical treatment protocols: methylprednisolone and GM1 ganglioside. The advent of improved high resolution radiologic studies has allowed a new dimension in the understanding of the physical and pathomechanical aspects of acute SCI. Advances in rehabilitation continue, allowing improved prognosis and long-term function. Prevention is clearly the best and most effective treatment of all. PMID- 1515696 TI - Autonomic disorders. PMID- 1515695 TI - Repair and regeneration: experimental aspects of spinal cord disease. AB - Regeneration of spinal cord neurons after injury depends on first, the presence of trophic factor(s) which prevent death, induce growth and maintain the viability of the neurone and second, the regenerating neurites must overcome glial scars, extracellular matrices and white matter barriers to reinnervate their target. Attempts at promoting regeneration by using grafts of prosthetic material, Schwann cells and neural tissue have largely been unsuccessful. Although growth could be induced, penetration of regenerating neurites through damaged areas of the spinal cord has been limited. There is as yet very little beneficial functional recovery. PMID- 1515697 TI - Neuropharmacology. PMID- 1515698 TI - Effect of cholesterol and its autooxidation derivatives on endocytosis and dipeptidyl peptidases of aortic endothelial cells. AB - The effects of cholesterol (CHO) and cholesterol autooxidation derivatives (CAD) on the endocytosis of cationized ferritin (CF) by endothelial cells have been investigated. The effect of both substances on the activity of lysosomal enzymes dipeptidyl peptidase I (DPP I) and dipeptidyl peptidase II (DPP II) was also studied. Treatment of rats with CAD induced striking alterations in the ultrastructure of endothelial cells and makes it impossible to analyze the effect of this toxin on endocytosis processes. In contrast, CHO-treated cells displayed a good ultrastructural preservation and showed an increased ability to endocyte ferritin, as compared with controls. Both DPP I and DPP II activities increased after 3 weeks of CAD or CHO treatment. Our results indicate that although CHO damage endothelial cells, the most important effects could be attributed to CAD which usually accompanies CHO-supplemented diets. PMID- 1515699 TI - Early in-vitro histological chondral differentiation. AB - In vitro chondrogenesis is possible in the chick embryo from stage 4 of Hamburger and Hamilton (1951), only 18-19 hours of incubation, before somite formation. In stage 4 of Hamburger and Hamilton (1951) the chondroblasts are placed laterally to the primitive streak and notochord cells are not necessary for cartilage differentiation. PMID- 1515700 TI - Localization of blood coagulation factors in the germinal centers of human Peyer's patches. AB - The immunohistochemical distribution of 15 blood coagulation factors in the germinal centers (GCs) of human Peyer's patches (PPs) was studied. Although factor VIII, active alpha-thrombin, and fibrinogen were hardly evident in the GCs, the majority of coagulation factors, such as kallikrein, high-molecular weight kininogen, factors XII, X, IX, VII, V, XIIIa and XIIIb, prothrombin, anti thrombin III and inactive alpha-thrombin were found, showing a lace-like staining pattern similar to that obtained with a monoclonal antibody, R4/23, specific for follicular dendritic cells (FDCs) in the GCs. By immunoelectron microscopy, positive reactions for factor X and XIIIa were found on the surfaces of FDCs, GC cells, and/or in the intercellular spaces of GCs, being especially marked on the surface of the labyrinth-like structure of FDCs. It is concluded that a majority of coagulation factors are localized in the GCs of human PPs. Furthermore, it is suggested that some of these coagulation factors have a close topographical relationship with FDCs. PMID- 1515701 TI - Intimal thickening in arterial autografts. Role of the adventitial layer. AB - In the present work, the repairing response of the iliac arterial wall is studied after carrying out autografts in segments of these vessels. The formation of the intimal hyperplasia, which occurred in all the cases, was followed at the biochemical level (tritium thymidine incorporation) and with light and electron microscopy. The adventitial layer showed great activity during the repairing process. We believe that it plays an important role not only in neoadventitial formation, but also in myointimal raising. PMID- 1515702 TI - Differential proliferation of rat aortic and mesenteric smooth muscle cells in culture. AB - Smooth muscle cells (SMC) from various arterial origins have been successfully maintained in culture. The present study evaluates the proliferative activity of aortic and mesenteric SMC in culture. Aortic and mesenteric SMC were obtained from male Wistar rats by explant and enzyme digestion techniques, respectively. Vascular SMC obtained by either method exhibited a characteristic hill-and-valley growth pattern in culture after confluence and were positively labelled with either anti-smooth muscle actin or myosin by an indirect immunofluorescent method. The rate of incorporation of thymidine into DNA and cell number counting were used as indices of proliferation in vitro. Vascular SMC from passages 4-33 were first synchronized with either Dullbecco's Modified Eagle's Medium (DME) or Ham's F-12 medium, supplemented with insulin-transferring-selenium (ITS), for 72 hours. SMC were then stimulated with 10% bovine serum for either 24 or 72 hours with the former processed for scintillation counting, the latter for cell number determination. The incorporation of tritiated thymidine into DNA following a 2 hour incubation was determined by scintillation counting after perchloric acid extraction. In terms of cell numbers, proliferative responses to bovine serum were determined by Coulter counting. Autoradiography was also carried out in some cultures to determine both thymidine and mitotic labelling indices. The rate of thymidine incorporation in aortic cells was 2-3 fold higher than in mesenteric cells. Aortic and mesenteric SMC lines exhibited similar cell cycle intervals in terms of total duration and individuals cycle parameters. However, the total thymidine index was higher in the aortic than mesenteric SMC.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1515703 TI - Sclerosing haemangioma of the lung. AB - The present paper describes a case of sclerosing haemangioma of the lung. Immunohistochemical analysis further supports its origin from respiratory epithelium, and confirms its minimal proliferative activity. PMID- 1515704 TI - Neurotrophic factor-like effect of FPF1070 on septal cholinergic neurons after transections of fimbria-fornix in the rat brain. AB - FPF1070 is an aqueous protein-free solution, which consists of 85% free amino acids and 15% small peptides. Our previous study showed a potent neurotrophic factor-like activity in cultured embryonic cells of dorsal root ganglia. The present study investigated whether FPF1070 regenerated the cholinergic cells in the medial septal nucleus after axonal transections by cutting the fimbria fornix. Fimbrial transection reduced the number of septal cholinergic cells by 30 +/- 3.6%, compared with the number on contralateral sides at 4 weeks. Intraperitoneal injections of FPF1070 caused 49.9 +/- 6.3% of the cholinergic neurons to survive. Furthermore, the cell sizes of the cholinergic neurons were significantly different: 16.4 +/- 4.2 microns, 14.3 +/- 3.8 microns in FPF1070 treatment and vehicle treatment, respectively. These results indicated that FPF1070 prevents the degeneration and atrophy of impaired cholinergic neurons by systemic administration. PMID- 1515705 TI - Effects of captopril on the development of rat doxorubicin nephropathy. AB - The effects of a daily administration of an anti-converting enzyme inhibitor. Captopril (CPT) (100 mg/kg/orally), on the development of functional and morphological alterations induced in rats by a single injection (7.5 mg/kg/iv) of Doxorubicin (DXR) (Adriamycin*), were investigated. Twenty-four-hour protein excretion, urine output, food intake, water intake, and body weight gain were measured weekly for 30 days. Transmission and scanning electron microscopy observations were performed on kidney samples after 30 days. Four groups were studied. Group 1 were control rats. Group 2 were rats injected with DXR. Group 3 were rats injected with DXR and treated with CPT for 30 days. Group 4 were rats injected with DXR and treated with CPT for 15 days (CPT treatment started 15 days after DXR injection). Group 1 did not show significant functional or morphological changes. Group 2 showed severe proteinuria, significant increase in urinary volume within 2 weeks, significant body weight reduction and diffuse morphological changes. These changes mainly consisted of podocyte swelling, severe foot process fusion, and presence of casts within tubular lumen. Group 3, with respect to group 2, showed a significant reduction of the 24 h protein excretion and urine output. This group displayed morphological changes similar to those observed in group 2, but with a focal distribution. Group 4 showed functional and morphological changes comparable with those of group 2. It is concluded that CPT partially inhibits the development of the functional and morphological damage induced by DXR in the rat kidney. However, CPT did not influence the natural development of nephropathy when treatment started 15 days after DXR injection. PMID- 1515706 TI - Etiology of the developing eye in myelencephalic blebs (my) mice. AB - The etiology of the eye defects in myelencephalic blebs (my) mutant mice has been poorly understood for almost seventy years. Embryos from 9 to 14 1/2 days of gestation were subjected to Alcian blue 8GX staining for acidic glycosaminoglycan deposition in basement membrane structures of the developing eye in my stock and control specimens. In addition 12 day embryos were subjected to avidinbiotin peroxidase labelling for laminin. At 9-9 1/2 days of gestation more Alcian blue positive extracellular matrix was found in the region between the optic vesicle and the overlying putative lens ectoderm in the my stock embryos. By 12 days, there was an irregular and lesser amount of deposition of glycosaminoglycans in the len's capsule and in the "inner limiting membrane" of the presumptive neural retina; however, the deposition of laminin appeared to be greater in the inner limiting membrane of the my eye. By 14 days, the damage to the eye in the my embryos can be quite extensive, and the deposition of glycosaminoglycans was very meager in this situation. It appears that irregular deposition of glycosaminoglycans in the extracellular matrix and possible increase in the amount of laminin in basement structures in my embryos indicate disruption of the normal histochemistry involved in the development of the eye. Altered histochemistry may in turn indicate changes in permeability between cells of the developing tissues which result in the blebbing. PMID- 1515708 TI - Peritoneal fine structure of inguinal hernia: a transmission electron microscope study. AB - Fine structure of normal human parietal peritoneum served as control data for recording changes in the fine structure of the peritoneum of hernial sacs. In these sacs, mesothelial cells retracted, rounded up and some of them eventually separated altogether to give rise to wide open intercellular spaces thus creating unhindered passageways (stomata) between the subserosal connective tissue and the cavity of the sacs. There was a considerable collagen build-up in the subserosal fibrous tissue of hernial sacs. Occurrence of this fibrosis is at variance with an accepted surgical concept which suggests a defect in collagen synthesis as the cause of herniation. In some sacs mesothelial nodules and/or peritoneal adhesions were present. Certain cytological changes in the mesothelial cells of hernial sacs showed features in common with cells of malignant tumours in general, and features mimicking malignant mesotheliomas in particular. This is in spite of the fact that thorough gross and light microscopic examination of operative specimens and cytological evaluation of peritoneal effusion failed to reveal any evidence of malignancy. Pathologists should be aware of the consummate ability of mesothelial cells to mimic carcinomas in order to avoid possible diagnostic errors. In this report, an electron micrograph of peritoneal adhesion is being published for the first time in the literature. A syncytium-like firm bond between adjoining mesothelial cells constituted the adhesion which is obviously an irreversible process. PMID- 1515707 TI - Changes in the ventral dermis and development of iridophores in the anadromous sea lamprey, Petromyzon marinus, during metamorphosis: an ultrastructural study. AB - The ultrastructural changes that take place in the ventral dermis along with the development of iridophores were examined in the anadromous sea lamprey, Petromyzon marinus, during metamorphosis. There is a disruption of all components of the ventral dermis and a reformation that results in a structure very similar to that prior to metamorphosis. Although not a dermal component, a layer of iridophores develops directly beneath the dermis during late metamorphosis. The dermal endothelium is lost by mid metamorphosis (stage 4) and the highly organized collagenous lamellae making up the bulk of the dermis become disrupted by the migration of fibroblasts into the region. Many of these fibroblasts are involved in the degradation of the lamellae. By stage 5 of metamorphosis some fibroblasts become highly active collagen synthesizing cuboidal shaped cells that align to form a layer above the reformed dermal endothelium. New lamellae are formed by these cuboidal cells which then divide and migrate into the lamellae where they assume the characteristic attenuated appearance of fibroblasts in the adult dermal lamellae region. Iridophores first appear during stage 5 directly beneath the dermal endothelium. Reflecting platelets develop from double membraned vesicles associated with the Golgi apparatus. By late metamorphosis, stacks of trapezoidal shaped platelets fill the cytoplasm of the iridophores. The significance of the changes in the dermis during metamorphosis are discussed. This work is part of a continuing series of studies on the connective tissues in the anadromous sea lamprey. PMID- 1515709 TI - The ependymal surface of the fourth ventricle of the rat: a combined scanning and transmission electron microscopic study. AB - The morphological features of the ependymal surface and supraependymal elements of the fourth ventricle of the rat were examined by scanning electron microscopy (SEM) and by the transmission electron microscopy (TEM). The results confirm the following aspects: 1) The presence of supraependymal elements and microvilli in the ependymal territories, including the sites where the cilia completely cover the ependymal surface; 2) The existence of cilia with oval or spherical thickenings together with supraependymal bulbs similar in size to those of the larger ciliary swellings; 3) Identification of the long supraependymal fibres with intermittent fusiform dilations observed under the SEM with the nerve fibres seen under the TEM; 4) The existence of intraventricular axodendritic synapses. PMID- 1515710 TI - Morphology of epiphyseal apparatus of a ranid frog (Rana Esculenta) AB - Morphological, histochemical and ultrastructural investigations on epiphyseal apparatus of Rana Esculenta were made. The most important findings were the following: 1) metaphyseal cartilage is localized inside proximal diaphyseal compact bone as a plug; 2) metaphyseal cartilage do not reduce in thickness during ageing; 3) metaphyseal cartilage do not show vascular invasion and do not mineralize in degenerative zone; 4) trabecular bone was not at all evident in this animal; 5) external periosteum is well vascularized and proliferates in correspondence to marginal epiphyseal end of the diaphyseal. From these results the hypothesis that the ranid frog bone growth is not due to metaphyseal metabolism (as in avian and mammals) but to bone periosteal marginal mineralization is reached. PMID- 1515711 TI - Retinal epithelial fine structure in the southern fiddler ray (Trygonorhina fasciata). AB - The morphology of the retinal epithelium (RPE), choriocapillaris and Bruch's membrane (complexus basalis) has been investigated by light and electron microscopy in an elasmobranch, the southern fiddler ray or guitarfish (Trygonorhina fasciata). The RPE consists of a single layer of cuboidal cells which display basal (scleral) infoldings as well as numerous apical (vitreal) finger-like processes which interdigitate with the photoreceptor outer segments. The lateral cell borders are relatively smooth and are joined in the mid-region by a series of tight junctions. Internally the RPE nucleus is large, vesicular and centrally located. Smooth endoplasmic reticulum (SER) is abundant while rough endoplasmic reticulum (RER) is scarce. Polysomes are however widespread and mitochondria are plentiful. Two unusual organelles are also noted. One consists of a membrane bound array of tubules while the other is a membrane bound structure consisting of a granular matrix with again an internal tubular array. This species possesses a choroidally located tapetum lucidum in the superior fundus and over this tapetal area, melanosomes are absent from the RPE cells. In non-tapetal locations a few melanosomes are present that do not appear to undergo photomechanical movements. Bruch's membrane is a pentalaminate structure with an almost continuous central elastic layer (lamina densa). The choriocapillaris forms a single layer of capillaries with a thin but only minimally fenestrated endothelium facing Bruch's membrane. PMID- 1515712 TI - Photoreceptor fine structure in the southern fiddler ray (Trygonorhina fasciata). AB - The fine structure of the retinal photoreceptors has been studied by light and electron microscopy in the southern fiddler ray or guitarfish (Trygonorhina fasciata). The duplex retina of this species contains only rods and single cones in a ratio of about 40:1. No multiple receptors (double cones), no repeating pattern or mosaic of photoreceptors and no retinomotor movements of these photoreceptors were noted. The rods are cylindrical cells with inner and outer segments of the same diameter. Cones are shorter, stouter cells with a conical outer segment and a wider inner segment. Rod outer segment discs display several irregular incisures to give a scalloped outline to the discs while cone outer segment discs have only a single incisure. In all photoreceptors a non-motile cilium joins the inner and outer segments. The inner segment is the synthetic centre of photoreceptors and in this compartment is located an accumulation of mitochondria (the ellipsoid), profiles of both rough and smooth endoplasmic reticulum, prominent Golgi zones and frequent autophagic vacuoles. The nuclei of rods and cones have much the same chromatin pattern but cone nuclei are invariably located against or particularly through the external limiting membrane (ELM). Numerous Landolt's clubs which are ciliated dendrites of bipolar cells as well as Muller cell processes project through the ELM, which is composed of a series of zonulae adherentes between these cells and the photoreceptors. The synaptic region of both rods (spherules) and cones (pedicles) display both invaginated (ribbon) synapses and superficial (conventional) synapses with cones showing more sites than the rods. PMID- 1515713 TI - Ultrastructural localisation of acid phosphatase in intestinal eosinophilic granule cells (EGC) of rainbow trout (Oncorhynchus mykiss) following degranulation with capsaicin. AB - Enzyme cytochemistry was used to investigate possible lysosome involvement in capsaicin induced degranulation of the eosinophilic granule cell (EGC) of the rainbow trout intestine. Three adult rainbow trout (Oncorhynchus mykiss) were injected intraperitoneally with capsaicin in a saline vehicle (0.5 micrograms.g-1 body weight). Following a 2 hour period of incubation, the fish were killed, and a mid portion of the intestine was dissected and fixed in cold glutaraldehyde buffered with sodium cacodylate. Vibratome sections were incubated in either reaction medium containing beta-glycerophosphate and cerium chloride in acetate buffer or substrate (beta-glycerophosphate) deficient control medium. Sections were then refixed in osmium tetroxide and processed for electron microscopy. Acid phosphatase was found to be localised within lysosomes. The enzyme was not found in the large cytoplasmic granules under normal or capsaicin-stimulated conditions. EGCs which had migrated to the lamina propria in response to the capsaicin stimulation had a distinct multivesicular granule morphology. These multivesicular granules did not contain acid phosphatase suggesting that this form of EGC degranulation is not a lysosomally mediated event. PMID- 1515714 TI - Effects of light deprivation on prolactin cells in golden hamsters: an immunoelectron microscopic study. AB - In the golden hamster light deprivation has been shown to induce gonadal regression and reduction of pituitary and plasma levels of prolactin (PRL). In the present study we examined changes in morphology and population ratios of three types of PRL cells 8 weeks after light deprivation, by means of blinding or exposure of hamsters to continuous darkness. In the pituitary of intact hamsters of either sex, which were entrained to a 14-h light: 10-h dark cycle, Type C cells with large secretory granules were the most numerous and Type A with smaller granules the least. After light deprivation the pituitary was found to contain remarkably atrophic PRL cells and showed a profound change in population ratio of PRL cell types, i.e., Type A cells prevailed over the other two types. Pituitary glands from light-deprived and concurrently pinealectomized hamsters exhibited structures and a population ratio of three types of PRL cells similar to those from intact animals. It is suggested that small-granule-containing PRL cells represent an inactive stage of PRL cells, whereas medium- and large-granule containing cells are functionally active cells. The atrophy of PRL cells can account for the decreased pituitary level of PRL in light-deprived hamsters reported previously. PMID- 1515715 TI - Percutaneous isolated liver perfusion for treatment of hepatic malignancy: preliminary report. AB - Chemotherapy for primary or metastatic hepatic malignancy is limited by poor tumor response and dose-related systemic toxicity. As an alternative to chemotherapy infusion by vein or by the hepatic artery, the authors have developed a percutaneous technique of isolated liver perfusion that allows the regional delivery of high-dose chemotherapy to the liver with little systemic toxicity. After placement of a hepatic artery infusion catheter, an 18-F double balloon catheter is placed into the inferior vena cava through the opposite femoral vein. Balloons are inflated above and below the hepatic veins, thus isolating hepatic venous outflow. The effluent passes through fenestrations in the catheter and is pumped through charcoal hemoperfusion filters where the drug is removed. The filtered blood is returned to the patient through the internal jugular vein. Fifteen treatments have been conducted in eight patients in a phase I dose-escalation study with use of 5-fluorouracil (5-FU). While it is premature to assess tumor response to isolated liver perfusion, the data demonstrate that the procedure is safe and is tolerated by patients. Pharmacokinetic studies show a 5-FU extraction of up to 85%, with minimal drug leakage into the systemic circulation. This technique shows potential for improving liver tumor response while decreasing systemic toxicity. PMID- 1515716 TI - Initial experience with percutaneous placement of the PAS port implantable venous access device. AB - The authors evaluated a new venous access port designed for peripheral venous insertion in the interventional radiology suite. Forty ports were placed in 40 patients in either the brachial, cephalic, or basilic vein under fluoroscopic guidance. These ports have been used for blood transfusion, blood sampling, parenteral nutrition, chemotherapy, and antibiotic therapy. The ports have been in use for 4,241 consecutive patients days. There have been no clinically apparent venous thrombotic complications and only one device-related infection. The cost and risk of complication are less than those for a surgically placed chest wall port, and the cosmetic result is excellent. This port has had excellent patient, nursing, and clinical acceptance. PMID- 1515717 TI - Wallstent migration following deployment in right and left bile ducts. AB - The Wallstent biliary endoprosthesis has recently been approved for treatment of malignant bile duct obstruction. Although minor changes in position have occurred, migration of these stents has been uncommon. The authors report a case in which migration occurred when stents were simultaneously deployed in the right and left bile ducts. Several mechanisms for this complication are postulated. PMID- 1515718 TI - Percutaneous renal ablation in children with end-stage renal disease. PMID- 1515719 TI - Low-dose urokinase regimen for the treatment of lower extremity arterial and graft occlusions: experience in 132 cases. AB - In a retrospective review, a low-dose urokinase (UK) infusion regimen (mean, 87,000 U of UK per hour and 100 U of heparin per hour) was evaluated for lower extremity arterial and graft occlusions. Results of 132 infusions in 111 patients were analyzed to determine efficacy, limb salvage, and complications. Angiographic success was achieved with 126 infusions (95%), and amelioration of presenting signs and symptoms was achieved after 116 infusions (88%). Patients who underwent additional percutaneous procedures were more likely to have a successful outcome. There was no significant difference in success rates for patients receiving low-dose heparin through the arterial sheath (n = 101) versus those receiving concomitant systemic heparinization (n = 29), (P = .08) [corrected]. Of 88 threatened extremities (with rest pain, cold, ulcers, or gangrene), nine were amputated (limb salvage = 90%), accounting for 82% (nine of 11) of amputations in the overall study. Patients with zero- or one-vessel runoff before infusion were more likely to require limb amputation compared with the group with two- or three-vessel runoff before infusion (P less than .01). Major periprocedural complications occurred in nine of 132 (7%) infusions, five of which necessitated specific surgery and/or transfusion for bleeding. Pericatheter thrombosis was not encountered in either subgroup. This standard local low-dose infusion represents a safe and effective treatment for lower extremity arterial and graft occlusions. PMID- 1515720 TI - Superior mesenteric artery embolism: treatment with intraarterial urokinase. AB - Four patients with a superior mesenteric artery (SMA) embolism were successfully treated with intraarterial urokinase. Angiography showed partial SMA occlusion by intraluminal thrombus in two cases and almost total occlusion in two cases. Laparotomy was performed in the latter two cases, one of which required resection of infarcted bowel. Several additional reports of partially occluding SMA emboli treated successfully with streptokinase were found in the literature. The use of intraarterial thrombolytic drugs is an important addition to the treatment of mesenteric embolism that, in some cases, can eliminate or simplify surgical management. PMID- 1515721 TI - Thromboembolectomy with the transluminal extraction catheter (TEC) as an adjunct to thrombolysis. AB - Multiple surgical and percutaneous interventional radiologic techniques have been used to restore blood flow in an acutely ischemic extremity. The transluminal extraction catheter (TEC) system was used as a mechanical thromboembolectomy device to supplement pharmacologic thrombolysis in one patient. In this case, 40 hours of direct intraarterial infusion of urokinase into the occluded vascular segments of a threatened lower extremity resulted in incomplete thrombolysis. Therefore, a 7-F TEC system was advanced percutaneously through the occluded vessels with restoration of luminal patency in all vessels treated. No distal embolization occurred. The TEC system facilitated prompt recanalization of vessels occluded by acute thrombus superimposed on atherosclerotic disease. PMID- 1515722 TI - Directional atherectomy treatment for hemodialysis access: early results. AB - The Simpson atherectomy device was used to treat 12 intragraft stenoses, six complete subclavian vein occlusions, and 14 venous outflow stenoses in 24 patients undergoing hemodialysis. Patients were followed up clinically and by means of venography at approximately 1, 3, 6, 9, and 12 months after treatment. Twenty-eight atherectomy specimens were examined histologically. Twenty-six (81%) of 32 lesions were treated with initial technical success. Including technical failures, seven (58%) of 12 intragraft stenoses are angiographically patent at a mean of 5.0 months and five (50%) of 10 are clinically patent at 6 months. Three (50%) of six subclavian veins are angiographically patent at a mean of 5.6 months, and four (67%) of six are clinically patent at 6 months. Three (21%) of 14 venous outflow stenoses are angiographically patent at a mean of 5.0 months and five (38%) of 13 are clinically patent at 6 months. Histologic examination showed neointimal fibromuscular hyperplasia in 26 of 28 lesions. When 30% or less angiographic residual stenosis is used as the criterion for initial technical success, directional atherectomy appears to be effective therapy for intragraft stenoses and, with balloon angioplasty, for some catheter insertion-related subclavian occlusions. Directional atherectomy appears to have a recurrence rate for venous outflow stenoses similar to that for balloon angioplasty when the same criterion is used. PMID- 1515723 TI - Transcatheter atrial septal defect occlusion devices: normal radiographic appearances and complications. AB - Three transcatheter atrial septal defect (ASD) occlusion devices have been used in clinical trials during the past decade: the Rashkind ASD occluder, the Lock Clamshell occluder, and the buttoned double-disk device. The normal radiographic appearance of these three devices and radiographic findings in complications are presented. Of 12 transcatheter ASD occlusions performed, the buttoned double-disk device was used in eight patients, the Rashkind ASD occluder in three, and the Lock Clamshell occluder in one. Complications included both improper placement and partial dislodgment of the Rashkind ASD occluder device (n = 2), fracture of a metal arm of the Lock Clamshell device (n = 1), and detachment of the buttoned double-disk device with embolization into the right pulmonary artery (n = 1). Knowledge of the normal radiographic appearance of ASD occlusion devices and the findings in various complications will be necessary for radiologists as transcatheter ASD closure becomes more commonplace. Chest radiography is the primary method of detecting short- and long-term complications in patients following transcatheter ASD closure. PMID- 1515724 TI - Vena caval occlusion after Simon nitinol filter placement: identification with MR imaging in patients with malignancy. AB - The prevalence of inferior vena caval occlusion associated with the Simon nitinol filter (SNF) was studied at two institutions in the follow-up of filters placed over a 13-month period. Twenty-four consecutive patients with defined indications (contraindication to anticoagulation with pulmonary embolism or deep venous thrombosis [DVT], recurrent pulmonary embolism despite anticoagulation, or extensive DVT [eg, iliofemoral]) underwent placement of a SNF. This patient group includes a high proportion with pelvic or renal malignancy (54%, 13 of 24) or a history of other malignancy. Of these 24, physical examination at follow-up identified 10 symptomatic patients with unilateral or bilateral leg swelling. Of these 10, magnetic resonance imaging, with spin-echo and gradient-echo techniques, demonstrated IVC occlusion in five patients (50%). These data suggest that vena caval occlusion following SNF placement occurs more commonly than previously recognized. Possible contributing factors include reduced venous inflow in patients with prior nephrectomy or pelvic neoplasms, pelvic venous compression by tumor mass, and hypercoagulable states. PMID- 1515725 TI - Traumatic lacerations of the aorta and great vessels with a normal mediastinum at radiography. AB - The possibility of a "normal" mediastinum at conventional chest radiography in a patient with a lacerated aorta or great vessel from blunt thoracic trauma has not been evaluated objectively. All 1991 members of the Society of Thoracic Radiology were sent a questionnaire asking for examples of such cases. A similar questionnaire was placed in the newsletter of the Society of Cardiovascular and Interventional Radiology. The literature also was reviewed for cases. Seventy eight of 327 questionnaires were returned with responses. Eight responders reported 12 examples of a normal mediastinum radiograph in a patient with a lacerated aorta. Review of the same radiographs by the authors yielded three normal and nine subtly abnormal mediastina. One additional normal radiograph was obtained of a patient with a lacerated great vessel. Another 16 cases of lacerated aortae (n = 12) and great vessels (n = 4) in patients with normal mediastina were found through a literature search; images from three of these were reviewed by the authors. Although this is an infrequent event, the mediastinum can be normal at plain chest radiography with traumatic lacerations of the aorta and great vessels. PMID- 1515726 TI - Localization of the portal vein for transjugular catheterization: percutaneous placement of a metallic marker with real-time US guidance. AB - Transjugular catheterization of the portal vein can be used to form a portosystemic shunt. Conventionally, the passage of a needle from the hepatic vein into the portal vein is performed with fluoroscopic monitoring only. Several methods to target the portal vein have been previously reported, including transhepatic venous catheterization, indirect portography (arterial catheterization), or skin marking based on ultrasound (US) mapping of portal landmarks. The authors used realtime US guidance to percutaneously place a small marking wire in the parenchyma next to the portal bifurcation. A 0.018-inch diameter, 5-mm-long platinum wire is delivered through a 22-gauge echo-tipped needle placed adjacent to the right portal vein. This marking wire enabled rapid entry into the portal vein, helped avoid extrahepatic puncture, and was useful during stent deployment and positioning. PMID- 1515727 TI - US-guided paraumbilical vein puncture: an adjunct to transjugular intrahepatic portosystemic shunt (TIPS) placement. AB - Transjugular intrahepatic portosystemic stent-shunt placement has shown great promise as a means of protal decompression in patients with severe portal hypertension. Passage of a needle from the hepatic venous system into the portal venous system during this procedure may be technically difficult; while it would be advantageous to precisely target the portal vein, most methods of localization are themselves technically difficult, risky, or time-consuming. The authors describe a method of localization of the portal vein that, when feasible, appears to be both safe and technically simple. This method involves percutaneous catheterization of a paraumbilical portosystemic collateral vein under sonographic guidance. PMID- 1515728 TI - Direct percutaneous ureteral approach for the treatment of ureteral stenosis or obstruction. AB - Two cases are presented in which conventional approaches did not permit dilation of and stent placement in obstructed ureters. In patients with iatrogenic ureteral laceration or rigid ureteral kinking, direct percutaneous translumbar puncture may provide a safe alternative. The authors' technique is described. PMID- 1515729 TI - Combined retrograde-antegrade ureteral stent passage: salvage procedure for a ureteral leak. AB - The authors describe a stent placement procedure for treatment of an infected ureteral leak after failure of traditional antegrade and retrograde approaches. In this procedure, a guide wire was placed across the distal ureteral segment into a urinoma with use of cystoscopic guidance. Thereafter, an antegrade approach was used to pass a wire loop snare, capture the guide wire, and withdraw it through the proximal ureter for subsequent stent passage. This approach allowed percutaneous stabilization of a ureteral leak in a patient who would have otherwise required immediate surgical repair. PMID- 1515730 TI - Comparison of filters in an oversized vena caval phantom: intracaval placement of a bird's nest filter versus biiliac placement of Greenfield, Vena Tech-LGM, and Simon nitinol filters. AB - For patients with an oversized inferior vena cava (IVC) (diameter greater than 28 mm, corrected for magnification) who require vena caval filtration for prophylaxis against pulmonary emboli, the accepted treatment has been the biiliac venous placement of Greenfield filters. Because of its wide strut span, the Bird's Nest filter (BNF) has been successfully placed in patients having an oversized IVC. However, the effects of the BNF on caval blood flow and its clot capturing ability in an oversized IVC are not clearly understood. The authors created a flow phantom simulating an oversized IVC with "iliac" tributaries of normal inner diameter to analyze flow turbulence, pressure gradients, and the clot-capturing ability of the BNF, tested within the "caval" segment of the phantom, and the Greenfield, Vena Tech-LGM, and Simon nitinol filters, tested in the "iliac" segments. All filters were tested for flow disturbances before and after clot capture. The authors' results demonstrate that within an oversized IVC, the BNF creates less flow disturbance and is less occlusive with clot capture than biiliac filters. The BNF displayed a clot-capturing ability equal to that of biiliac filters. Thus, for patients with an oversized IVC, these results suggest that placement of a single intracaval BNF is preferable to biiliac placement of filters. PMID- 1515731 TI - In vitro comparison of the spiral Z stent and the Gianturco Z stent. AB - A new spiral Z stent is described, and its characteristics are compared in vitro with those of the modified Gianturco Z stent. The spiral Z stent has a more uniform expansile force throughout its effective length; is more compressible, thus allowing for use of a smaller introductory catheter; and is more stable than the modified Z stent. Flexibility of both stent types is similar. Advantages of the spiral Z stent promise to be beneficial for clinical use. PMID- 1515732 TI - Percutaneous nucleotomy with CT and fluoroscopic guidance. AB - Automated percutaneous diskectomy was performed with use of computed tomographic (CT) and fluoroscopic monitoring. Degenerative disease of the intervertebral disk was treated with local administration of anesthesia and use of a nucleotome. One hundred ten patients with neurologic symptoms and morphologic changes of one segment were selected for treatment. Previous conservative therapy had been unsuccessful. Patients with completely prolapsed and sequestered fragments of herniated disks ("uncontained disk"), narrow intervertebral spaces, posterior osteophytes, diseased facet joints, and spinal stenoses were not considered candidates for percutaneous nucleotomy (PNT). After PNT, 82% of the patients had complete remission of their neurologic symptoms; Lasegue sign was negative or improved in 92%. In 18% (20 patients), the symptoms did not improve sufficiently; 11% (12 of 110) of these patients underwent surgical nucleotomy. There were no serious complications, in particular, no injuries to vital structures (nerves, thecal sac, arteries, veins), except for one case of spondylodiskitis. Guiding PNT with CT and fluoroscopy provides a safe procedure with good clinical results. The addition of CT has shortened the operation but increased over-all procedure time. In the future, a shift to outpatient treatment may offset the additional time and cost of including CT guidance. PMID- 1515733 TI - Steel coil embolization supplementing filter placement in a patient with a duplicated inferior vena cava. AB - Anatomic anomalies involving the inferior vena cava (IVC) can present both diagnostic and therapeutic challenges when percutaneous placement of a filter is considered. A patient with a duplicated IVC was treated with placement of a filter in the right-sided IVC and steel coil embolization of a smaller left-sided IVC. PMID- 1515734 TI - Retrieval of intravascular foreign bodies with the snare and catheter capture technique. AB - The authors report two cases of retrieval of iatrogenically placed intravascular metallic foreign bodies: a guide wire in the abdominal aorta and a guide-wire fragment in the inferior vena cava. The foreign bodies were retrieved with use of a new approach described as the "snare and catheter capture technique." This technique is useful with guide wires that are too stiff to safely remove doubled over. PMID- 1515735 TI - Interventionists save PET. PMID- 1515736 TI - Permanence and the dynamics of biological systems. AB - A basic question in mathematical biology concerns the long-term survival of each component, which might typically be a population in an ecological context, of a system of interacting components. Many criteria have been used to define the notion of long-term survival. We consider here the subject of permanence, i.e., the study of the long-term survival of each species in a set of populations. These situations may often be modeled successfully by dynamical systems and have led to the development of some interesting mathematical techniques and results. Our intention here is to describe these and to consider their application to several of the most frequently used models occurring in mathematical biology. We particularly wish to include and cover those models leading to problems that are essentially infinite dimensional, for example reaction-diffusion equations, and to make the discussion accessible to a wide audience, we include a chapter outlining the fundamental theory of these. PMID- 1515737 TI - A new method for regularization of the inverse problem of electrocardiography. AB - The inverse problem of electrocardiography (specifically, that part concerned with the computation of the ventricular surface activation isochrones) is shown to be formally equivalent to the problem of identification and measurement of discontinuities in derivatives of body surface potentials. This is based on the demonstration that such measurements allow localization of the relative extrema of the ventricular surface activation map (given a forward problem solution), which in turn restricts the space of admissible solution maps to a compact set. Although the inverse problem and the problem of identifying derivative discontinuities are both ill-posed, it is possible that the latter may be more easily or justifiably resolved with available information, particularly as current methods for regularizing the inverse problem typically rely on a regularization parameter chosen in an a posteriori fashion. An example of the power of the approach is the demonstration that a recent Uniform Dipole Layer Hypothesis-based method for producing the ventricular surface activation map is largely independent on that hypothesis and capable in principle of generating maps that are very similar in a precise sense to those that would result from the usual epicardial potential formulation (assuming the latter were capable of producing intrinsic deflections in computed epicardial electrograms sufficiently steep to accurately compute the activation map). This is consistent with the preliminary success of the former method, despite the significant inaccuracy of its underlying assumption. PMID- 1515738 TI - Properties of the solutions to certain equations arising in the central core model of the renal medulla. AB - We discuss the mathematical properties of the solutions to two of the differential equations that arise in the central core model of the renal medulla. Explicit solutions are obtained for a particular functional form of the flux of solute. PMID- 1515739 TI - Branching process with emigration--a genetic model. AB - Solution of a genetic improvement problem under the model of assortative mating is proposed. This has been achieved through the technique applied to a branching process incorporating a generation-dependent emigration component. The model explains a population subject to culling against genes governing undesirable characters and this work has been tried for a diploid population with two alleles at a single locus, which may be extended to the multilocus case. PMID- 1515740 TI - Hopf bifurcation in three-species food chain models with group defense. AB - Three-species food-chain models, in which the prey population exhibits group defense, are considered. Using the carrying capacity of the environment as the bifurcation parameter, it is shown that the model without delay undergoes a sequence of Hopf bifurcations. In the model with delay it is shown that using a delay as a bifurcation parameter, a Hopf bifurcation can also occur in this case. These occurrences may be interpreted as showing that a region of local stability (survival) may exist even though the positive steady states are unstable. A computer code BIFDD is used to determine the stability of the bifurcation solutions of a delay model. PMID- 1515741 TI - The effects of averaging on the basic reproduction ratio. AB - This paper formalizes the process of averaging the mixing patterns of behaviorally distinct individuals or groups. This averaging process is shown to decrease or leave unaltered the basic reproduction ratio R0 in epidemiological models with symmetric transmission between groups. PMID- 1515742 TI - Epidemic and demographic interaction in the spread of potentially fatal diseases in growing populations. AB - The spread of a potentially fatal infectious disease is considered in a host population that would increase exponentially in the absence of the disease. Taking into account how the effective contact rate C(N) depends on the population size N, the model demonstrates that demographic and epidemiological conclusions depend crucially on the properties of the contact function C. Conditions are given for the following scenarios to occur: (i) the disease spreads at a lower rate than the populations grows and does not modify the population growth rate: (ii) the disease initially spreads at a faster rate than the population grows and lowers the population growth rate in the long run and the following three subscenarios are possible: (iia) the population still grows exponentially, but at a slower rate; (iib) population growth is limited, but the population size does not decay; (iic) population increase is converted into population decrease. PMID- 1515743 TI - A mathematical model for the growth and classification of a solid tumor: a new approach via nonlinear elasticity theory using strain-energy functions. AB - Medically, tumors are classified into two important classes--benign and malignant. Generally speaking, the two classes display different behaviour with regard to their rate and manner of growth and subsequent possible spread. In this paper, we formulate a new approach to tumor growth using results and techniques from nonlinear elasticity theory. A mathematical model is given for the growth of a solid tumor using membrane and thick-shell theory. A central feature of the model is the characterization of the material composition of the tumor through the use of a strain energy function, thus permitting a mathematical description of the degree of differentiation of the tumor explicitly in the model. Conditions are given in terms of the strain energy function for the processes of invasion and metastasis occurring in a tumor, being interpreted as the bifurcation modes of the spherical shell, which the tumor is essentially modeled as. Our results are compared with actual medical experimental results and with the general behavior shown by benign and malignant tumors. Finally, we use these results in conjunction with aspects of surface morphogenesis of tumors (in particular, the Gaussian and mean curvatures of the surface of a solid tumor) in an attempt to produce a mathematical formulation and description of the important medical processes of staging and grading cancers. We hope that this approach may form the basis of a practical application. PMID- 1515744 TI - Predictions of antagonistic muscular activity using nonlinear optimization. AB - Optimization theory is used more often than any other method to predict individual muscle forces in human movement. One of the limitations frequently associated with optimization algorithms based on efficiency criteria is that they are thought to not provide solutions containing antagonistic muscular forces; however, it is well known that such forces exist. Since analytical solutions of nonlinear optimization algorithms involving multi-degree-of-freedom models containing multijoint muscles are not available, antagonistic behavior in such models is not well understood. The purpose of this investigation was to study antagonistic behavior of muscles analytically, using a three-degree-of-freedom model containing six one-joint and four two-joint muscles. We found that there is a set of general solutions for a nonlinear optimal design based on a minimal cost stress function that requires antagonistic muscular force to reach the optimal solution. This result depends on a system description involving multijoint muscles and contradicts earlier claims made in the biomechanics, physiology, and motor learning literature that consider antagonistic muscular activities inefficient. PMID- 1515745 TI - Interpreting consensus sequences based on plurality rule. AB - Our goal is to help researchers interpret the results of a function, based on the concept of plurality rule, that calculates a consensus of a profile of molecular bases. By expressing the plurality rule function as a composition of simpler functions, we obtain both an algorithm to calculate the consensus result and an upper bound on the number of nonequivalent results. Consequently, when used to analyze molecular sequences such as DNA or RNA, the plurality rule function yields at most 48 nonequivalent consensus results. For problems of reasonable size, we describe an algorithm to calculate the probability that each consensus result would occur if the bases were equally likely to appear at every position of the plurality rule function's input profile. PMID- 1515746 TI - A two-state recurrent stochastic model with time-dependent transition rates. AB - The two-state recurrent stochastic model with time-independent transition rates is generalized to a model with time-dependent transition rates. The rates can be any general function of external time, that is, any general function of the calendar time in which the process unfolds. Formulas for the state transition probabilities, the proportion of individuals in a particular state at time t, the distribution function, and the expectation of the number of individuals in a particular state at time t are derived. PMID- 1515747 TI - The attractiveness of the Droop equations. AB - The Droop equations are a system of three coupled, nonlinear ordinary differential equations describing the growth of a microorganism in a chemostat. The growth rate of the organism is limited by the availability of a single nutrient. In contrast to the better known Monod equations, the nutrient is divided into external and internal cellular pools. Only the internal pool can catalyze growth. This paper proves that the Droop equations are globally stable. Based on a single combination of parameters, either the chemostat organism goes extinct or it tends to a fixed, positive concentration. PMID- 1515748 TI - Efficient optimal decomposition of a sequence into disjoint regions, each matched to some template in an inventory. AB - Given an amino acid sequence, we discuss how to find efficiently an optimal set of disjoint regions (substrings, domains, modules, etc.), each of which can be matched to some element of a predefined inventory containing, for example, consensus sequences, protosequences, or protein family profiles. A two-stage approach to sequence decomposition, consisting of the detection of all acceptable matches followed by the construction of an optimal subset of compatible matches, leads to computational difficulties. When the problem is reformulated in terms of network comparisons, it can be solved in time quadratic in the length of the sequence and linear with the number of templates in the inventory, by a single pass of a dynamic programming algorithm. This method has the advantage that the criterion for acceptable matches can be relaxed without materially affecting computing time. Except under special conditions it is more efficient than previous segmentation methods based on dynamic programming. PMID- 1515749 TI - The growth of pure and simple microbial competitors in a moving distributed medium. AB - The dynamics of pure and simple competition between two microbial species are examined for the case of interaction arising in a distributed and nonstagnant environment. The environment is modeled as a tubular reactor. It is shown that for relatively small values of the dispersion coefficient (i.e., for small, but nonzero, backmixing of the medium), the two competing populations can coexist in a stable steady state. It has been assumed that the species grow uninhibited and that if there are maintenance requirements they are satisfied from endogenous sources. From numerical studies it has been found that a necessary condition for coexistence is that the net specific growth rate curves of the two competitors cross each other at a positive value of the concentration of the rate-limiting substrate. The model equations have been numerically solved by using the methods of orthogonal and spline collocation. PMID- 1515750 TI - A 10-year prognosis for childhood allergic rhinitis. AB - The prognosis of allergic rhinitis was studied in 154 children aged 3-17 years at diagnosis by means of a detailed questionnaire administered 8-11 years later. The symptoms had completely disappeared in only 15 (10%) patients. The conjunctival symptoms, however, had disappeared or were controlled successfully by topical drug therapy in almost all, and 77 (50%) were managing without medication for allergic rhinitis. Twenty-five (23%) of the 110 children with seasonal allergic rhinitis had a perennial disease at follow-up, in contrast to seven (16%) of 44 with perennial allergic rhinitis originally who had only seasonal symptoms at follow-up. Asthma or wheezing had developed in 29 cases (19%) and was more common (p less than 0.01) among those with perennial allergic rhinitis (15 of 44) than among those with seasonal allergic rhinitis (14 of 110). No significant association was found between age at onset of symptoms, family history of atopic disease or type of treatment for allergic rhinitis and allergic rhinitis still present at follow-up or development of asthma during the observation period. PMID- 1515751 TI - Regressed retinopathy of prematurity: the relationship between clinical risk factors of the newborn period and regressed retinopathy of prematurity severity in a preterm born population of Stockholm county 1976-81. AB - In a retrospective study, clinical risk factors of the neonatal period were correlated with the severity of regressed retinopathy of prematurity (ROP) in a population of preterm infants (bw less than 1500 g and or gestational age less than 33 weeks). At the age of 5-11 years 134 out of 528 preterm born infants (25.4%) were found to be under ophthalmic care. Reliable information on eye fundus status could be obtained in 105 of them. Regressed ROP was found in 61, the moderate form in 48 (9.1%) and the severe form in 13 (2.5%) patients. Twelve patients (2.3%) had visual acuity of less than 0.3 on the worst eye and two (0.4%) of these patients were blind from ROP. Twenty-four clinical factors of the newborn period were correlated with the severity of regressed ROP. The results suggest that long oxygen exposure in combination with other factors interfering with retinal vasotonus are associated with the degree of the disease developed. PMID- 1515752 TI - Re-evaluation of the whey protein/casein ratio of human milk. AB - Total casein subunits as well as whey proteins were quantitated in human milk samples during lactation. Two independent methods were used: precipitation at pH 4.3 in the presence of Ca2+ followed by Kjeldahl analysis and polyacrylamide gradient gel electrophoresis (PAGGE) followed by densitometric scanning. Both methods yielded similar results: casein synthesis is low or absent in early lactation, then increases rapidly and subsequently decreases. The concentration of whey proteins decreases from early lactation and continues to fall. These changes result in a whey protein/casein ratio of about 90:10 in early lactation, 60:40 in mature milk and 50:50 in late lactation. These observations indicate that the synthesis and/or secretion of caseins and whey proteins is regulated by different mechanisms. In addition, the relative proportion of the different beta- and kappa-casein subunits was found to vary throughout lactation. PMID- 1515753 TI - Immunoglobulin G subclasses in human colostrum, milk and saliva. AB - Previous studies have suggested local production of IgG4 in human colostrum and mature milk. We extended these observations to examine all IgG subclasses in mammary secretions and in saliva, a mucosal secretion. In human colostrum and milk, the geometric mean percentages of IgG contributed by IgG2 were 44% and 43%, respectively, and by IgG4, 6% in both. These percentages are significantly increased compared to the contributions in matched plasma, 29% for IgG2 and 2% for IgG4. The contribution of IgG1 (47%) and IgG3 (less than 4%) were decreased compared to plasma which contained 64% IgG1 and 6% IgG3. Similarly, in salivary secretions the percentages of IgG contributed by IgG2 and IgG4 were increased compared to serum while the percentage of IgG1 was decreased. IgG3 was not measurable in any saliva specimen by the technique used. These data demonstrate that IgG subclass distribution in two separate mucosal secretions is uniquely different from that in matching plasma or serum. PMID- 1515754 TI - Supplementation of an adapted formula with bovine lactoferrin: 1. Effect on the infant faecal flora. AB - The development of the infant faecal flora was studied over the first three months of life in infants receiving breast milk, a modern adapted formula and adaptations of this formula. Breast-fed infants developed a flora rich in Bifidobacterium sp. Facultative anaerobes were ubiquitous, but in relatively small numbers within the diet group. Other obligate anaerobes, such as Clostridium sp. and Bacteriodes sp. were rarely isolated. Standard formula produced a flora rich in bifidobacteria, but the growth of facultative organisms was not suppressed by this diet. Clostridium sp. and Bacteroides sp. were more common in this feeding group. After the addition of lactoferrin at 10 mg/100 ml to the formula diet, a flora similar to that of the standard formula-fed babies was achieved. Lactoferrin at 100 mg/100 ml was able to establish a "bifidus flora" in half of the babies given this formula, but only at age three months. Clostridium sp. and Bacteroides sp. were common faecal isolates from babies receiving both the lactoferrin diets. PMID- 1515755 TI - Blood T and B lymphocyte subpopulations in healthy infants and children. AB - Monoclonal antibodies and flow cytometry are now used routinely in the diagnosis of many malignant diseases and primary and secondary immunodeficiency states. Technical advances have improved the identification of blood lymphocyte subsets and reliable normal values are now obtainable. Such values have been reported for adults but not for children. We report both absolute and percentage normal values for lymphocytes and their subsets in infants and children of different ages. Our findings show that the absolute and percentage values for most lymphocyte markers differ substantially not only between children and adults, but also between children from different age groups. In infants, erythroid cell contamination of Ficoll gradient-density isolated mononuclear cells must be removed to obtain reliable flow cytometry values. PMID- 1515756 TI - Gastroesophageal reflux in children with recurrent abdominal pain. AB - In this study we investigated the presence of gastroesophageal reflux in children with recurrent abdominal pain and its possible relationship to food intolerance associated duodenal inflammation. Twenty-four-hour intra-esophageal pH monitoring, an endoscopic duodenal biopsy and a small bowel 51Cr-EDTA permeability test were performed in 25 children with recurrent abdominal pain. In 14 cases (56%) the pH monitoring was abnormal, pointing to the presence of pathological gastroesophageal reflux. Treatment of gastroesophageal reflux in the latter patients resulted in resolution or improvement of abdominal pain in 10 cases (71%). Gastroesophageal reflux did not appear to be associated with either intestinal permeability to 51Cr-EDTA or duodenal biopsy findings. We conclude that pathological gastroesophageal reflex is a frequent finding in children with recurrent abdominal pain, that it is unrelated to duodenal inflammation and that there might be a causal relationship between pathological gastroesophageal reflux and recurrent abdominal pain in children. PMID- 1515757 TI - Polymerase chain reaction for detection of Mycobacterium tuberculosis. AB - Rapid diagnosis of tuberculosis is essential, and therefore we use a polymerase chain reaction. In this report, we describe two cases of tuberculous lymphadenitis in childhood. Although histopathological findings were not specific for tuberculosis in both cases, distinct positive bands were amplified. For DNA diagnosis of tuberculosis, a lysis method of extracting chromosomal DNA from lipid-rich cell walls of mycobacteria is of critical importance. We made use of a simple lysozyme-proteinase K treatment for biopsied tissues. Although this extraction procedure was less efficient than those reported previously, it was considered sufficient for detecting mycobacterial DNA with the use of a highly sensitive polymerase chain reaction. We conclude that DNA amplification in combination with lysozyme lysis can be used routinely in clinical laboratories as a rapid and sensitive test for the diagnosis of tuberculosis. PMID- 1515758 TI - Evaluation of captopril versus reserpine and frusemide in treating hypertensive children with acute post-streptococcal glomerulonephritis. AB - We have evaluated the effect of oral captopril versus a combination of oral reserpine and frusemide in the treatment of 20 children with post-streptococcal glomerulonephritis (APGN) with hypertension. Captopril produced a significantly greater reduction in systolic and diastolic blood pressure in both the standing and supine positions than reserpine + frusemide at 0.75, 1, 1.25, 8, 24, 48 and 72 h after initiating treatment. Neither postural hypotension nor reflex tachycardia accompanied the therapeutic effect of captopril. Blood urea, serum creatinine and creatinine clearance did not change significantly after therapy in either study group. Three days after initiating treatment, the 24 h urinary catecholamine output increased significantly in children who received captopril but did not change in children treated with frusemide and reserpine. PMID- 1515759 TI - High density lipoprotein cholesterol and total cholesterol in children with asthma and allergic rhinitis. AB - Serum high density lipoprotein cholesterol and total cholesterol were studied in 15 children with allergic rhinitis, 45 asymptomatic asthmatic children and 16 children with acute asthmatic attacks. The latter were also studied in their asymptomatic phase. Two control groups of children with minor anatomical defects and those with acute pneumonia with respiratory distress were also studied. The serum concentrations of high density lipoprotein cholesterol were significantly higher (p less than 0.001) and those of total cholesterol lower (p less than 0.001) in children with respiratory allergy when compared to controls. The concentration of high density lipoprotein cholesterol increased and that of total cholesterol decreased during acute asthma. PMID- 1515760 TI - A follow-up study of the diet of Finnish diabetic adolescents. AB - Changes with age and time in energy-adjusted food consumption and nutrient intake of 74 diabetic subjects initially aged 12-17 years were studied. Food consumption was measured by the 48-h recall method. During the three-year follow-up (from 1985 to 1988), the proportion of carbohydrate of total energy intake decreased from 49% to 47%, that of fat increased from 33% to 36% and that of protein decreased slightly. The densities of fibre and several vitamins decreased in the diet of the diabetic adolescents. These unfavourable changes in the diet of diabetic adolescents took place with increasing age and duration of diabetes, while virtually no changes with time were detected. PMID- 1515761 TI - Collagen type II in Langer-Saldino achondrogenesis: absence of major abnormalities in a less severe case. AB - Collagen extracted either from cartilage or synthesized in vitro was analyzed to identify possible molecular defects in the cartilaginous matrix of a male fetus suffering from a mild form of type II achondrogenesis (Langer-Saldino). The tissue architecture of the patient's cartilage was markedly altered and showed numerous fibrous vascular canals which were focally stained by antibodies against collagens I and III. Collagen II was present, although heterogenously distributed throughout the cartilaginous matrix. Upon electrophoretic separation, however, the patient's femoral head cartilage showed the presence of collagens II, IX and XI only, which was similar to an age-matched control. The hydroxyproline/hydroxylysine ratio of collagen II of the patient was not significantly different from that of the control. Likewise, the compositions of collagens synthesized by cultured chondrocytes as well as fibroblasts were similar in the patient and the control. The results provide strong evidence that, in the present mild case of Langer-Saldino achondrogenesis, collagen II is expressed and regularly hydroxylated at its lysyl residues. This may indicate that cartilage components other than collagen II may be responsible for the altered tissue organization observed. Along with previous observations, our data suggest that the degree of biochemical matrix alterations may be related to the severity of the clinical phenotype. PMID- 1515762 TI - Oral zinc as initial therapy in Wilson's disease: two years of continuous treatment in a 10-year-old child. AB - Two years of continuous therapy promoted a significant overall amelioration in a 10-year-old boy affected by an hepatic form of Wilson's disease in which zinc sulphate was the sole therapy. In particular, liver function returned to normal and hepatic histology also improved. The parameters characterizing copper metabolism were kept under good control, and a decrease in copper concentration was found in both erythrocytes and liver. The copper balance study performed during the 25th month of treatment showed that oral zinc was still efficiently inhibiting the intestinal absorption of copper. No side effects have been reported so far. PMID- 1515763 TI - Rett syndrome: the late infantile regression period--a retrospective analysis of 91 cases. AB - The late infantile regression period of Rett syndrome was analysed in a consecutively collected series of females, born 1945-87 (median 17 1/2 years), fulfilling the diagnostic criteria for classic Rett syndrome. For general information, data from 91 girls and women were used (group A), while more detailed analysis was based on the youngest 20, all born during the last decade (group B). Median ages at onset of developmental stagnation (stage I) were 11 (5 24) and 10 (5-18) months for groups A and B, respectively. Loss of acquired skills (stage II) began at 19 (12-36) and 17 (13-25) months, and lasted for 19 (2 53) and 13 (2-32) months. Onset of the period of loss was distinctly marked in 43%, dramatic in 16% and insidious in 41%. Gross motor delay and aberrant behaviour raised the first suspicions of disease, while a more specific pattern comprising a triad of manifestations, i.e. contact/communication, hand use/skill, babble/words, characterized the loss of acquired skills. Although development invariability came to a definite break at a crucial stage of maturation, an "awakening" (stage III) and return of interest to act and interact astonishingly followed the period of withdrawal. Apraxia was found in all, but some use of the hands could be enticed in engaging and non-demanding situations. The observed preference for use of the left hand (9/11), compared to the right (2/11), suggested a reflection of an underlying dysfunction/disease process, also displayed as spike activity in left central leads in EEGs from 13/20 girls. PMID- 1515764 TI - Influence of surgical treatment of scoliosis in children with spina bifida on ambulation and motoric skills. AB - The influence on motoric skills of surgical treatment of scoliosis in 14 children with myelomeningocele was studied. Fifty percent of the children had increased flexion contractures of the hips at follow-up, and all but one patient had impaired motor ability. There was no influence on activities of daily life, but 57% of children had lost some of their ambulation capacity. Postoperative physiotherapy is highly advisable. Intensive attempts to treat these children conservatively to prevent scoliosis progression is suggested. PMID- 1515765 TI - Congenital dislocation of the hip: a prospective study comparing ultrasound and clinical examination. AB - Screening for congenital dislocation of the hip by standard clinical methods and ultrasound was compared prospectively in 1503 newborns (1291 girls and 212 boys). A total of 82.8% of the hips (78.8% of the infants) had well developed acetabulae, 14.5% (17.2% of the infants) were shallow (immature) and 2.7% (4.1% of the infants) were dysplastic. Within 1-3 months 96.7% of the infants with clinically stable, but immature hips normalized, while 3.3% did not improve or worsened, and therapy was therefore initiated. Indications for treatment included dysplastic and/or clinically unstable hips, and a higher number of newborns were treated during the study period than in 1982-85 (31.2 vs 19.7 per 1000, p = 0.0002). Thirty-seven percent of the patients had both clinical and ultrasound findings compatible with congenital dislocation of the hip, while the decision to treat was based on clinical findings alone in 25.0% and on ultrasound findings in 38.0%. Infants born during the study period of nine months had a low incidence of late congenital dislocation of the hip compared with our earlier reported results from 1982-85 (0.9 vs 3.5 per 1000, p = 0.012). The study demonstrated major discrepancies between clinical and ultrasound evaluation of hips in the newborn, and the role of ultrasound in the screening for congenital dislocation of the hip requires further evaluation. PMID- 1515766 TI - Aplasia cutis congenita of the scalp without other defects in three siblings. PMID- 1515767 TI - Transverse myelitis following mumps in children. AB - Although acute transverse myelitis is a rare complication of mumps, it is relatively well documented. We describe a child who developed mumps associated acute transverse myelitis and who subsequently recovered completely. To our knowledge, only 13 cases have been reported in children. This case is compared with 13 previously reported patients. PMID- 1515768 TI - Precision of gestational age assessment in the neonate. AB - The precision of the Ballard scale for assessing gestational age (GA) was evaluated in a consecutive sample of 227 preterm and/or low-birth-weight neonates. Each newborn was rated independently by two neonatologists and the difference in GA estimation between them was computed. The estimated precision was not high, the 95% tolerance interval estimate being as large as 7.4 weeks. The precision of the neurologic and physical parts of the scale was poorer than that of the complete scale (95% of differences less than 10.5 and 9.2 weeks respectively), and more influenced by the type of delivery. These findings are not unexpected from statistical theory, and cast doubts on the use of only the physical part of the Ballard scale in assessing GA, since greater accuracy could be accompanied by reduced precision. PMID- 1515769 TI - Exposure assessment for electric and magnetic fields. AB - Exposure assessment for extremely low frequency (ELF) electric and magnetic fields (EMF) is discussed. It is suggested that such assessments can be designed by attempting to mimic the receptor's experience of interest. Present efforts are, however, hampered by the lack of clearly defined human health effects, or even important interaction mechanisms, which might be used to define the appropriate exposure measure, the experience of interest. The state of the art of ELF EMF exposure assessment is described, including the use of surrogates, models, and available instrumentation. Data indicate that magnetic field levels in the home are of the order of 0.1 microT and that nonoccupational total exposures may best be predicted by levels in the bedroom. Occupational exposures may be orders of magnitude higher where high currents are present. PMID- 1515770 TI - Regional differences in dietary intake of environmental pollutants in Japan. AB - In order to study regional differences in the dietary intake of environmental pollutants in Japan, we measured the daily intake ingested via food (the main route for pollutant intake) and analyzed the data by multivariate analysis. Daily mean samples were collected by the duplicate method from 25 women per area in 5 cities in both northern and southern Japan in July, 1987. Cadmium, lead, benzo(a)pyrene, hexachlorobenzene, DDT, chlordane isomers, and the total amount of the isomers were determined for typical pollutants. The data were statistically analyzed by multivariate analysis. Regional differences in the daily intake of environmental pollutants were studied by discriminant analysis. The eigenvalues of the functions 1 and 2, which accounted for 84.8% of variance, were 0.647 and 0.221, respectively. The function 1 was related to regional differences in the intake of environmental pollutants in the northern and southern regions of Japan. The statistical distance calculated from the intake of environmental pollutants correlated well with the geographical distance. The coefficients of the canonical discriminant function 1 were large in the order of lead (Pb) and the total amount of chlordane isomers (T-CLD). The regional difference was assumed to be due to the intake of Pb in the north and the intake of T-CLD in the south. Other pollutants, however, did not contribute to the observed regional difference. The study shows that performing multivariate analysis by computer provides a useful means for processing a large amount of data and can provide important information for data analysis in environmental health. PMID- 1515771 TI - The measurement of salivary cadmium by electrothermal atomic absorption spectrophotometry and its use as a biological indicator of occupational exposure. AB - We have examined the potential use of salivary cadmium measurements for the biological monitoring of occupational cadmium exposure, paying particular attention to the contamination risks associated with such measurements. We have developed a method for the direct determination of cadmium in saliva by graphite furnace atomic absorption spectrophotometry, which minimizes the risk of contamination during sample preparation and analysis. The limit of detection is 0.6 nmoll-1, which is sufficiently sensitive to discriminate between unexposed and occupationally exposed individuals. The method has been employed to measure cadmium levels in saliva samples collected by two different methods from an unexposed population, a group of ex-workers previously exposed to cadmium (Group 1), and two groups of currently exposed workers (Groups 2 and 3). Salivary cadmium levels were significantly raised in both of the groups of currently exposed individuals (group 2 median (Md) = 17 nmoll-1, group 3 Md = 70 nmoll-1, p greater than 0.0001), and in past workers with previous long-term exposure (Group 1 Md = 2.5 nmoll-1, p greater than 0.001) when compared with an unexposed population. The results suggest that the measurement of salivary cadmium may reflect recent exposure to the metal. However, considerable care must be taken in collecting samples because a risk of contamination during sampling is apparent with procedures commonly used for saliva collection, and for this reason the applicability of such measurements for biological monitoring is limited. PMID- 1515772 TI - Wind velocity effects on sampling rate of NO2 badge. AB - The effects of wind velocity on a sampling rate of a nitrogen dioxide (NO2) diffusive badge were experimentally determined using a turntable. The use of a turntable permits the collection of the large amounts of data that are needed for statistically reliable results at several wind velocities in one experiment. The regression model for the wind effect determined by these experiments was closely correlated with data previously gathered from experiments using wind tunnels. Experiments at two different relative humidities, 35% and 60%, were performed and analyzed by a simple least square regression model. A multi-regression model containing two independent variables, wind velocity and relative humidity, also was developed. The multi-regression model was useful at relative humidity between 20% and 60% and wind velocity between 0 and 7 meter per second (m/sec). PMID- 1515773 TI - Validation of a terrestrial food chain model. AB - An increasingly important topic in risk assessment is the estimation of human exposure to environmental pollutants through pathways other than inhalation. The Environmental Protection Agency (EPA) has recently developed a computerized methodology (EPA, 1990) to estimate indirect exposure to toxic pollutants from Municipal Waste Combuster emissions. This methodology estimates health risks from exposure to toxic pollutants from the terrestrial food chain (TFC), soil ingestion, drinking water ingestion, fish ingestion, and dermal absorption via soil and water. Of these, one of the most difficult to estimate is exposure through the food chain. This paper estimates the accuracy of the EPA methodology for estimating food chain contamination. To our knowledge, no data exist on measured concentrations of pollutants in food grown around Municipal Waste Incinerators, and few field-scale studies have been performed on the uptake of pollutants in the food chain. Therefore, to evaluate the EPA methodology, we compare actual measurements of background contaminant levels in food with estimates made using EPA's computerized methodology. Background levels of contaminants in air, water, and soil were used as input to the EPA food chain model to predict background levels of contaminants in food. These predicted values were then compared with the measured background contaminant levels. Comparisons were performed for dioxin, pentachlorophenol, polychlorinated biphenyls, benzene, benzo(a)pyrene, mercury, and lead. PMID- 1515774 TI - Pretesting questionnaires in the laboratory: an alternative approach. PMID- 1515775 TI - 66th meeting of the American Thyroid Association, Inc. Rochester, Minnesota, September 23-26, 1992. Abstracts. PMID- 1515776 TI - [Problems in clinical research]. AB - In recent years, the requirements of society towards the quality of research have increased. Especially in the perspective of European integration, ethical and conceptual problems have to be revisited. Clinical research is alimented by technical development and the results of fundamental and pharmacological research. The obligation of converting the most recent knowledge into conventional treatment is the driving force of development. Clinical research is fraught with multiple risks, mainly the risks incurred by patients enrolled in clinical studies, and the risks of drawing erroneous conclusions from badly designed studies. This is the reason why the organization of clinical studies must satisfy the highest quality standards. Prospective randomized double-blind studies are doubtless the best design although they usually involve the difficult problem of patient information. As concerns publications, the picture may be distorted. Thus all the studies should be published exhaustively. Clinical research is thus a great challenge from both the intellectual and the ethical points of view. PMID- 1515777 TI - [Lymphoscintigraphy with (123)I-marked epidermal growth factor in cervix cancer]. AB - Several malignant neoplasms express high levels of epidermal growth factor receptors. The aim of this study was to assess whether 123I-labeled epidermal growth factor can concentrate in lymph node metastases of squamous cell carcinomas of the cervix. 14 patients with advanced cervical cancer were selected because of their high probability of lymph node metastases. Planar scintigrams were recorded from the lower and upper abdomen following subcutaneous injection of 123I-labeled epidermal growth factor into the web space of each foot. Scintigraphic images were interpreted without knowledge of computerized tomography scan (n = 13) and ultrasound (n = 9) results from the pelvic lymph nodes. In 2 patients, histological verification was performed by diagnostic biopsy of pelvic lymph nodes. Nodal involvement was confirmed by computerized tomography for 4 of the 11 positive scans and by ultrasound for 2. In 11 out of 14 patients an increased uptake of 123I-labeled epidermal growth factor could also be seen in the primary tumour. Our findings suggest that targeting of cervical cancer lymph node metastases can be achieved by in vivo binding of 123I labeled epidermal growth factor with receptors on tumour cell surfaces. PMID- 1515778 TI - [Modern reproduction medicine. Reflections of a clinician]. PMID- 1515779 TI - [Early diastolic incisures in uteroplacental blood vessels. Experiences in patients with uneventful pregnancy and labor]. AB - The frequency of diastolic notching in uteroplacental arteries was examined in a collective of 510 patients with uneventful pregnancies and deliveries. Notching appeared to be more frequent in the uterine than arcuate artery. It was seen to increase as pregnancy progressed and was markedly higher in the third compared with the second trimester. Uteroplacental notching occurred more frequently unilaterally and mainly affected contralateral sites of the placenta. Bilateral and retroplacental notching was the exception in normal pregnancies. PMID- 1515780 TI - [Cytologic cancer prevention with smears of the uterine cervix and endocervical canal in pregnancy]. AB - This study was performed to evaluate the importance of obtaining prepartum Papanicolaou smears routinely. 1,417 patients receiving pregnancy care had normal prenatal Pap smears. 88 (5.85%) had abnormal prepartum Pap smears. Thirteen (14.8%) of the abnormal smears showed squamous dysplasia, 2 (2.3%) showed an adenocarcinoma or squamous invasive carcinoma. The results of this study support the practice of performing Pap smears during prenatal care. PMID- 1515781 TI - [Ethics of the physician]. PMID- 1515782 TI - [Indications and timing of Doppler screening]. PMID- 1515783 TI - Why cigarette advertising should be banned. PMID- 1515784 TI - Microalbuminuria. PMID- 1515785 TI - Patterns of hospital medical staffing. PMID- 1515786 TI - Behcet's disease. PMID- 1515787 TI - British surgeon infected with HIV. PMID- 1515788 TI - Management of sudden bereavement in the accident and emergency department. AB - OBJECTIVE: To assess facilities available for the suddenly bereaved in accident and emergency departments and variations in care of bereaved relatives. DESIGN: Postal questionnaire survey. SETTING: England and Wales. SUBJECTS: All 98 accident and emergency departments treating over 50,000 patients a year, 78 of which replied. MAIN OUTCOME MEASURES: Number of departments with specific facilities, staff training, and procedures for dealing with bereavement. RESULTS: 60 hospitals had a specific room for bereaved relatives; the remainder used multipurpose rooms. In 49 hospitals relatives were taken to the room by a nurse with sole responsibility for caring for them. In 40 hospitals the nurse stayed with the relatives and 66 updated relatives on the patient's condition. Facilities for viewing the body privately were poor, and relatives often had to ask to be left alone. 25 departments gave no written information on bereavement and only four routinely followed up relatives. Further training was requested by staff in 44 departments. CONCLUSIONS: Although facilities could be improved, immediate care of relatives is good. Care over subsequent weeks and preparation for this period is invariably inadequate. PMID- 1515789 TI - Audit of a tuberculosis contact tracing clinic. AB - OBJECTIVE: To determine the efficiency of tuberculosis contact tracing in South Glamorgan 1987-9. DESIGN: Review of records of contact tracing clinic and of data from the Mycobacterium Reference Unit. The clinic's practice was compared with 1983 British Thoracic Society's recommendations. SETTING: Health authority tuberculosis control programme. MAIN OUTCOME MEASURES: Proportion of contacts screened, follow up attendance rates, number of secondary cases detected, and quality of record keeping. RESULTS: 101 index patients and 611 contacts were identified. 596 (97.5%) contacts were screened, of whom 139 should not have been. Of 356 contacts requiring a Heaf test, 237 were tested, seven refused the test, and 112 had chest radiography without a Heaf test. 95 contacts were unnecessarily tested. 87 contacts had chest radiography unnecessarily and seven should have had radiography but did not. 34 contacts were given follow up appointments inappropriately and seven were overlooked for follow up. Tuberculosis was diagnosed in five asymptomatic contacts, all at initial screening and all close contacts of index patients with pulmonary disease. CONCLUSION: Inadequacy of data, non-adherence to contact tracing guidelines, and failure to define the term highly infectious index case resulted in many contacts being unnecessarily screened or followed up. IMPLICATIONS: The efficiency of tracing contacts would be improved by specifying smear results and ethnic origin of the index case on the notification form, clearly classifying contacts as close or causal, and clearly defining the term highly infectious. PMID- 1515790 TI - Must diabetes be a fatal disease in Africa? Study of costs of treatment. AB - OBJECTIVE: To estimate the costs of diagnosis and treatment of diabetes in Tanzania. DESIGN: Costs estimated from the reported and recorded experience of patients with newly presenting diabetes in 1989-90 and of diabetic patients first seen in 1981-2. SETTING: Muhimbili Medical Centre, Dar es Salaam. SUBJECTS: 464 patients (315 men and 149 women). 262 patients diagnosed during 1 September 1989 31 August 1990 (group 1) and 202 during 1 June 1981-31 August 1982 (group 2). RESULTS: The average annual direct cost of diabetes care in 1989-90 was $287 for a patient requiring insulin and $103 for a patient not requiring insulin. Purchase of insulin accounted for 68.2% ($156) of the average annual outpatient costs for patients requiring insulin. For patients not requiring insulin the cost of oral hypoglycaemic drugs and treatment of chronic complications and infections accounted for 42.5% ($29.3) and 48.8% ($33.7) of costs respectively. Cost of outpatient care of diabetic patients for the whole of Tanzania was estimated at $2.7m, *75,128 (32.2%) of which was for insulin. Doctors' and nurses' costs accounted for 0.2% of total costs of outpatient care. The annual direct inpatient care costs were estimated at $1.25m. Around 0.2% of the Tanzanian population aged 15 years and over used the equivalent of 8% of the total government health expenditure, which was $47,4088,382. CONCLUSION: Diabetes places a severe strain on the limited resources of developing countries. If African patients with diabetes have to pay for their treatment most will be unable to do so and will die. PMID- 1515791 TI - Hyponatraemia and death or permanent brain damage in healthy children. AB - OBJECTIVE: To determine if hyponatraemia causes permanent brain damage in healthy children and, if so, if the disorder is primarily limited to females, as occurs in adults. DESIGN: Prospective clinical case study of 16 affected children and a review of 24,412 consecutive surgical admissions at one medical centre. PATIENTS: 16 children (nine male, seven female; age 7 (SD 5) years) with generally minor illness were electively hospitalised for primary care. Consultation was obtained for the combination of respiratory arrest with symptomatic hyponatraemia (serum sodium concentration less than or equal to 128 mmol/l). MAIN OUTCOME MEASURES: Presence, gender distribution, and classification of permanent brain damage in children with symptomatic hyponatraemia in both prospective and retrospective studies. RESULTS: By retrospective evaluation the incidence of postoperative hyponatraemia among 24,412 patients was 0.34% (83 cases) and mortality of those afflicted was 8.4% (seven deaths). In the prospective population the serum sodium concentration on admission was 138 (SD 2) mmol/l. From three to 120 inpatient hours after hypotonic fluid administration patients developed progressive lethargy, headache, nausea, and emesis with an explosive onset of respiratory arrest. At the time serum sodium concentration was 115 (7) mmol/l and arterial oxygen tension 6 (1.5) kPa. The hyponatraemia was primarily caused by extrarenal loss of electrolytes with replacement by hypotonic fluids. All 16 patients had cerebral oedema detected at either radiological or postmortem examination. All 15 patients not treated for their hyponatraemia in a timely manner either died or were permanently incapacitated by brain damage. The only patient treated in a timely manner was alive but mentally retarded. CONCLUSIONS: Symptomatic hyponatraemia can result in high morbidity in children of both genders, which is due in large part to inadequate brain adaptation and lack of timely treatment. PMID- 1515792 TI - First use of heroin: changes in route of administration over time. PMID- 1515793 TI - Relation between quality of cervical smears and probability of abnormal results. PMID- 1515794 TI - Guillain-Barre syndrome after treatment with streptokinase. PMID- 1515795 TI - Nifedipine induced gingival abscesses. PMID- 1515796 TI - Rhabdomyolysis due to combined treatment with lovastatin and cholestyramine. PMID- 1515797 TI - Visual problems in the elderly population and implications for services. AB - OBJECTIVE: To determine the prevalence of visual disability and common eye disease among elderly people in inner London. DESIGN: Cross sectional random sample survey. SETTING: Inner London health centre. SUBJECTS: Random sample of people aged 65 and over taken from practice's computerised age-sex register. MAIN OUTCOME MEASURES: Presenting binocular Snellen 6 m distance acuity and best monocular 3 m Sonksen-Silver acuity to classify prevalence of blindness by World Health Organisation criteria (less than 3/60 in better eye) and American criteria for legal blindness (better eye equal to 6/60 or less) and of low vision by WHO criteria (best acuity 6/18) and visual impairment by American criteria (less than 6/12 or 20/40 but greater than 6/60 or 20/200 in better eye). Principal cause of visual loss by diagnosis, referral indication by cause to hospital eye service, and proportion of cases known to primary care. RESULTS: 207 of 288 (72%) eligible people were examined. 17 (8%) housebound subjects were examined at home. The prevalence of blindness was 1% by WHO criteria and 3.9% by American criteria. The prevalence of low vision (WHO criteria) was 7.7%. The prevalence of visual impairment (American criteria) was 10.6%. Cataract accounted for 75% of cases of low vision. Only eight out of 16 patients with low vision were known by their general practitioner to have an eye problem. 56 subjects (27%) would probably have benefited from refraction. Comparisons with studies in the United States and Finland suggested higher rates in this sample, mainly due to the prevalence of disabling cataract. CONCLUSION: There seems to be a considerable amount of undetected ocular disease in elderly people in the community. PMID- 1515798 TI - Effect of unexpected demolition announcement on health of residents. AB - OBJECTIVE: To examine the impact of an unexpected announcement of the demolition of a housing estate on the health of the area's residents. DESIGN: Study of general practitioner consultation rates of the estate's residents after the announcement compared with those of other areas and with those of the previous year. SETTING: General practices in Runcorn, Cheshire. PATIENTS: 17,000 patients on lists of the two group practices serving the estate and surrounding area. MAIN OUTCOME MEASURE: Relative weekly consultation rates with general practitioners. RESULTS: The mean adjusted odds ratio for consultation was 1.12 (SD 0.12) when demolition was expected and 0.877 (0.05) when it was not (t = 5.94, p less than 0.001). The difference remained after the adjustment for the fall in the estate's population was removed (t = 3.7, p less than 0.01). CONCLUSION: Announcement of the estate's demolition adversely affected residents' health. PMID- 1515799 TI - Guidelines on the management of tuberculosis and HIV infection in the United Kingdom. Subcommittee of the Joint Tuberculosis Committee of the British Thoracic Society. PMID- 1515800 TI - Molecular genetics of cancer. PMID- 1515801 TI - ABC or colorectal disease. Constipation. PMID- 1515802 TI - Recording HIV status on police computers. PMID- 1515803 TI - Recording HIV status on police computers. PMID- 1515804 TI - Recording HIV status on police computers. PMID- 1515805 TI - Cholera: getting the message across. PMID- 1515806 TI - Work related disorders of the upper limb. PMID- 1515807 TI - Blood glucose and diabetic retinopathy. PMID- 1515808 TI - Storing vaccines at the correct temperature. PMID- 1515809 TI - Missed neuroleptic malignant syndrome. PMID- 1515810 TI - Missed neuroleptic malignant syndrome. PMID- 1515811 TI - Cardiac stress during transurethral prostatectomy. PMID- 1515812 TI - Pregnancy and fasting during Ramadan. PMID- 1515813 TI - Psychological treatments in cancer patients. PMID- 1515814 TI - Checking quality of health care records. PMID- 1515815 TI - Consultants' communications with general practitioners. PMID- 1515816 TI - Medical response to disasters overseas. PMID- 1515817 TI - Medical response to disasters overseas. PMID- 1515818 TI - First among women. PMID- 1515819 TI - The health of the nation. PMID- 1515820 TI - What future for the regions? PMID- 1515821 TI - Performance related pay for hospital doctors. PMID- 1515822 TI - Campylobacter: epidemiological paradoxes. PMID- 1515823 TI - Reducing mortality from meningococcal disease. PMID- 1515824 TI - Anhedonia: exclusion from the pleasure dome. PMID- 1515825 TI - Don't mention AIDS in the American election campaign. PMID- 1515826 TI - Meningococcal infections: reducing the case fatality rate by giving penicillin before admission to hospital. AB - OBJECTIVE: To determine whether parenteral penicillin given before admission to hospital reduces the case fatality rate in patients with meningococcal disease. DESIGN: Retrospective analysis of 46 consecutive patients admitted to hospital with meningococcal disease from January 1986 to March 1991. SETTING: District general hospital. MAIN OUTCOME MEASURE: Hospital case fatality rate. RESULTS: None of the 13 patients given parenteral penicillin by the referring doctor before admission died, compared with eight deaths (24%) in 33 patients admitted without such treatment. CONCLUSION: Parenteral penicillin given before admission probably contributed to a reduction in the case fatality rate from meningococcal disease, and primary care physicians should be encouraged to give such treatment immediately on suspicion of the diagnosis before transferring the patient to hospital. Public health physicians are well placed to inform and alert general practitioners of the potential benefit of this action. PMID- 1515827 TI - Early treatment with parenteral penicillin in meningococcal disease. AB - OBJECTIVE: To measure the effect of parenteral antibiotics given before admission to hospital on mortality and on bacteriological investigations in meningococcal disease. DESIGN: Retrospective review of hospital notes and laboratory and public health medicine department records. SETTING: Three health districts in south west England. SUBJECTS: Patients with meningococcal disease in Gloucester district presenting between 1 January 1982 and 31 December 1991 (n = 190); patients with meningococcal disease in Plymouth (n = 118) and Bath (n = 73) districts presenting between 1 January 1988 and 31 December 1991 (total = 381). MAIN OUTCOME MEASURE: Number of deaths from meningococcal disease. RESULTS: Parenteral antibiotic given by general practitioners was associated with a substantial reduction in mortality (from 9% to 5%; relative risk 0.6, 95% confidence interval 0.2 to 1.5); patients with a rash were more likely to be given parenteral antibiotics, and mortality was further reduced (from 12% to 5%; 0.5, 0.2 to 1.4). In a district where such treatment was regularly encouraged its use increased from 5% to 40% of cases over 10 years (p = 0.00001). Treatment with parenteral antibiotics before admission made isolation of meningococci from blood and cerebrospinal fluid less likely but did not affect nasopharyngeal cultures. CONCLUSIONS: General practitioners should carry benzylpenicillin in their emergency bags at all times and should administer it promptly, preferably intravenously, whenever meningococcal disease is suspected, unless the patient has had an anaphylactic reaction to penicillin. Specimens for culture should include a nasopharyngeal swab. PMID- 1515828 TI - Follow up of patients presenting with fatigue to an infectious diseases clinic. AB - OBJECTIVES: To determine the symptomatic and functional status during follow up of patients referred to hospital with unexplained fatigue and to identify patient variables associated with persistent functional impairment. DESIGN: Follow up by postal questionnaire six weeks to four years (median 1 year) after initial clinical assessment of patients referred to hospital during 1984-8. SETTING: Infectious diseases outpatient clinic in a teaching hospital. PATIENTS: 200 consecutive patients with fatigue of uncertain cause for at least six weeks; 177 fulfilled the inclusion criteria. MAIN OUTCOME MEASURES: Findings at initial assessment; current symptoms, beliefs about the cause of illness, coping behaviours emotional disorder, social variables including membership of self help organizations, and degrees of recovery and functional impairment from questionnaire responses. RESULTS: 144 (81%) patients returned completed questionnaires. Initial assessment did not indicate the cause of fatigue, other than preceding infection. The proportion of patients with functional impairment was significantly smaller with longer follow up (33% (11/33) at two to four years, 73% (29/40) at six weeks to six months; chi 2 for trend = 12.5, df = 1; p less than 0.05). Functional impairment was significantly associated with belief in a viral cause of the illness (odds ratio = 3.9; 95% confidence interval 1.5 to 9.9), limiting exercise (3.2; 1.5 to 6.6), avoiding alcohol (4.5; 1.8 to 11.3), changing or leaving employment (3.1; 1.4 to 6.9), belonging to a self help organization (7.8; 2.5 to 23.9), and current emotional disorder (4.4; 2.0 to 9.3). CONCLUSIONS: Short term prognosis for recovery of function was poor but improved with time. Most patients had made a functional recovery by two years after initial clinic attendance. Impaired functioning was more likely with certain patient characteristics. Prospective studies are required to clarify whether these associations are the consequences of a more disabling illness or indicate factors contributing to impaired function. PMID- 1515829 TI - Association between postpartum thyroid dysfunction and thyroid antibodies and depression. AB - OBJECTIVE: To define the relation between mood and autoimmune thyroid dysfunction during the eight months after delivery. DESIGN: Double blind comparison of the psychiatric status of women positive and negative for thyroid antibodies. Clinical examination and blood sampling for free triiodothyronine and thyroxine, thyroid stimulating hormone, and thyroid antibody concentrations at four weekly intervals. Psychiatric assessment at six, eight, 12, 20, and 28 weeks post partum. SETTING: Outpatient department of district hospital. PATIENTS: 145 antibody positive women and 229 antibody negative women delivering between August 1987 and December 1989. MAIN OUTCOME MEASURES: Thyroid status. Number of cases of mental ill health by the general health questionnaire, research diagnostic criteria, Hamilton 17 item depression scale, hospital anxiety and depression scale, and Edinburgh postnatal depression scale. RESULTS: Six weeks after delivery the general health questionnaire showed 62 (43%) antibody positive women and 65 (28%) antibody negative women had mental ill health (chi 2 = 8.18, p less than 0.005). Follow up of 110 antibody positive and 132 antibody negative women showed significantly greater depression by research diagnostic criteria in antibody positive women (47%) than antibody negative women (32%) regardless of thyroid dysfunction. Antibody positive women showed higher mean scores for depression on the Hamilton (6.01 v 3.89, p = 0.0002), Edinburgh (7.45 v 5.92, p = 0.031), and hospital depression scales (4.95 v 3.79, p = 0.003). CONCLUSION: Depressive symptoms are associated with positive thyroid antibody status in the postpartum period. PMID- 1515830 TI - Contamination of skin and clothing of accident and emergency personnel. PMID- 1515831 TI - General practice and accident and emergency department care: does the patient know best? PMID- 1515832 TI - Changing site distribution of colorectal cancer. PMID- 1515833 TI - Mesalazine induced lupus-like syndrome. PMID- 1515834 TI - Thrombocytopenia associated with lithium carbonate. PMID- 1515835 TI - Attitudes to tracing and notifying contacts of people with HIV infection. PMID- 1515836 TI - ABC of colorectal diseases. Anal cancer. PMID- 1515837 TI - Venous air embolism associated with removal of central venous catheter. PMID- 1515838 TI - Potential endocervical pathogens before termination. PMID- 1515839 TI - Potential endocervical pathogens before termination. PMID- 1515840 TI - Potential endocervical pathogens before termination. PMID- 1515841 TI - Heterosexual spread of HIV infection. PMID- 1515842 TI - Treatment of allergy. PMID- 1515843 TI - Cardiac arrest associated with flumazenil. PMID- 1515844 TI - Symptoms after accelerated immunisation. PMID- 1515845 TI - Monitoring ambulatory blood pressure in general practice. PMID- 1515846 TI - Maintenance treatment with methadone. PMID- 1515847 TI - Multiple sclerosis: diagnostic optimism. PMID- 1515848 TI - Reformulated Omnopon. PMID- 1515849 TI - Adrenaline in allergic emergencies. PMID- 1515850 TI - Cataract in developing countries. PMID- 1515851 TI - Visual problems in the elderly population. PMID- 1515852 TI - Altitude induced illness. PMID- 1515853 TI - Long term problems after obstetric epidural anaesthesia. PMID- 1515854 TI - Site of injection for vaccination. PMID- 1515855 TI - Patterns of hospital medical staffing. PMID- 1515856 TI - Use of Lucozade and glucagon by ambulance staff in hypoglycaemia. PMID- 1515857 TI - Patient's charter in outpatient services. PMID- 1515858 TI - Unnecessary hospitalization in a psychiatric rehabilitation unit. PMID- 1515859 TI - Patient's charter in outpatient services. PMID- 1515860 TI - "Gold standard" is an appropriate term. PMID- 1515861 TI - Dispensing doctors. PMID- 1515862 TI - Medical abortion. PMID- 1515863 TI - Health and education in developing countries. PMID- 1515864 TI - Medical abortion. PMID- 1515865 TI - Effect of reduced temperatures and brefeldin A on prolactin secretion and on subcellular distribution of the secretory product and membrane antigens in GH3 pituitary cells. AB - The effects of reduced temperatures (20, 15 or 10 degrees C) and brefeldin A (BFA) on prolactin (PRL) secretion in the GH3 rat pituitary cell line have been compared. Both treatments inhibit PRL release to different extents. Ultrastructural immunocytochemistry reveals that, depending on the treatment, PRL is blocked at different steps during its intracellular transit. The temperatures of 20 and 15 degrees C block the PRL transport at one face of the Golgi stacks whereas both the temperature of 10 degrees C and BFA treatment induce an arrest of PRL at the level of the rough endoplasmic reticulum (RER) cisternae. Moreover, exposure to 10 degrees C or BFA induces an accumulation of a specific Golgi membrane antigen in the dilated RER structures. However, although disorganized and no longer definable under BFA treatment, the Golgi apparatus remains visible at 10 degrees C. These two last treatments cause also an increase in the number of partly rough, partly smooth tubular structures tentatively called 'paired cisternae'. PMID- 1515866 TI - Distribution of intramembranous particles and filipin-sterol complexes in the spermatid and spermatozoon of Culex quinquefasciatus (Culicidae). AB - A freeze-fracture study was carried out on spermatid and spermatozoon of the mosquito Culex quinquefasciatus. In the spermatid plasma membrane few and randomly distributed intramembranous particles were observed. In the spermatozoon the density of intramembranous particles was higher on the P- than on the E fracture face of the plasma membrane. Two populations of particles were observed. Large particles (about 15 nm in diameter) are regularly arranged in double rows as a zipper-line, longitudinally oriented in relation to the main cell axis. These strands of particles were observed in the posterior head region, mainly associated with the E-fracture face. Filipin was used to analyse the presence and distribution of cholesterol in thin sections and freeze-fracture replicas. Filipin-sterol complexes were not homogeneously distributed throughout the spermatozoon plasma membrane. They were more abundant on the P-fracture face of the membrane lining the nuclear region. The results obtained show that Culex spermatozoon differs from those of other species in that its plasma membrane exhibits only a membrane domain, the zipper-line, localized in the postacrosomal region. PMID- 1515867 TI - Lymphocyte calmodulin and its participation in the stimulation of T lymphocytes by mitogenic lectins. AB - Calmodulin was purified from human tonsillar lymphocytes utilizing calcium dependent binding of calmodulin to fluphenazine-Sepharose. The molecular weight and phosphodiesterase activation of the lymphocyte calmodulin were very similar to those of purified bovine brain calmodulin. Trifluoperazine (TFP), a calmodulin inhibitor, suppressed lymphocyte stimulation as assessed by 3H-thymidine incorporation into DNA of lectin-stimulated lymphocytes. TFP had no effect on the early 45Ca2+ uptake induced by mitogenic lectins, although this latter was inhibited by verapamil which also suppressed the 3H-thymidine incorporation. The results are in keeping with the interpretation that the inhibition of T cell stimulation by TFP was not due to suppression of Ca2+ uptake, but due to inactivation of Ca(2+)-calmodulin complex which might be formed subsequent to Ca2+ entry into the cell. PMID- 1515868 TI - Differential temperature sensitivity of cultured cells from cartilaginous or bone origin. AB - The effects of long-term exposure to hyperthermia were studied on several cell cultures of cartilaginous or bone origin after a 4-day treatment at 40 degrees C. Chondrocytes proliferation, as well as mitochondrial activity were not modified by these culture conditions (40 degrees C) but protein content and cell volume were increased. In contrast, the proliferative capacity of osteoblasts, MC3T3.E1 a and ROS 17/2.8 was decreased and their protein content, cell volume and mitochondrial activity were increased. Chondrocytes appeared to be thermoresistant, and osteoblastic cells thermosensitive. Furthermore, temperature sensitivity was greater for the continuous established osteoblastic cell line MC3T3.E1 and for the cancerous established osteoblastic cell line ROS 17/2.8 than for chondrocytes. PMID- 1515869 TI - Initiation and stability of reentry in two coupled excitable fibers. AB - Reentry in the heart is the repeated excitation of the same tissue by a single excitation wave; it is responsible for several types of cardiac arrhythmia. The simplest model which permits the phenomenon of reentry is two laterally coupled excitable fibers; in this paper we examine such a model in order to establish a basis for the understanding of the fundamental physical processes underlying the process of reentry. Two versions of the FitzHugh-Nagumo equations are used to develop complementary numerical and analytical results for the coupled fiber model. On the basis of numerical studies, regions of qualitatively different behaviour are mapped in the parameter space of excitation threshold and coupling strength between the fibers, and the effect of the rate of recovery is explored. Some of these regions are also obtained analytically, in good agreement with the numerical results. Finally, the results are discussed in the light of recent work on the role of the anisotropy of cardiac tissue in the initiation of reentrant activity in the heart. PMID- 1515870 TI - Consensus sequences based on plurality rule. PMID- 1515871 TI - Modelling the electrotonic structure of starburst amacrine cells in the rabbit retina: a functional interpretation of dendritic morphology. AB - A detailed morphometric analysis of a Lucifer yellow-filled Cb amacrine cell was undertaken to provide raw data for the construction of a neuronal cable model. The cable model was employed to determine whether distal input-output regions of dendrites were electrically isolated from the soma and each other. Calculations of steady state electrotonic current spread suggested reasonable electrical communication between cell body and dendrites. In particular, the centripetal voltage attenuation revealed that a synaptic signal introduced at the distal end of the equivalent dendrite could spread passively along the dendrite and reach the soma with little loss in amplitude. A functional interpretation of this result could favour a postsynaptic rather than a presynaptic scheme for the operation of directional selectivity in the rabbit retina. On the other hand, dendrites of starburst amacrine cells process information electrotonically with a bias towards the centrifugal direction and for a restricted range of membrane resistance values the voltage attenuation in the centripetal direction suggests that the action of these dendrites can be confined locally. A functional interpretation of this result favours a presynaptic version of Vaney's cotransmission model which attempts to explain how the neural network of starburst amacrine cells might account for directionally selective responses observed in the rabbit retina. PMID- 1515872 TI - Flow-induced deformation from pressurized cavities in absorbing porous tissues. AB - The behaviour of a cavity during an injection of fluid into biological tissue is considered. High cavity pressure drives fluid into the neighbouring tissue where it is absorbed by capillaries and lymphatics. The tissue is modelled as a nonlinear deformable porous medium with the injected fluid absorbed by the tissue at a rate proportional to the local pressure. A model with a spherical cavity in an infinite medium is used to find the pressure and displacement of the tissue as a function of time and radial distance. Analytical and numerical solutions for a step change in cavity pressure show that the flow induces a radial compression in the medium together with an annular expansion, the net result being an overall expansion of the medium. Thus any flow induced deformation of the material will aid in the absorption of fluid. PMID- 1515873 TI - The role of cytokines in graft-versus-host reactions and disease. AB - CD4+ and CD8+ T lymphocytes are responsible for the initiation of graft-versus host disease (GVHD) which limits the efficacy of human allogeneic bone marrow transplantation. Activated T cells are a rich source of cytokines in vitro, and many of these same molecules are also found in graft-versus-host reactions (GVHR) and GVHD. However, T cells are not the only source of these soluble mediators. Cytokines control the actions of many cell types both in vitro and in vivo, so these soluble factors can easily influence the actions of both the engrafted hematopoietic cells and the host's cells. The complex manner in which cells and cytokines interact in GVHR and GVHD is reviewed here. We speculate that cytokine cascades play major roles in many aspects of GVHR and GVHD. PMID- 1515874 TI - The role of conditioning regimens in homing of transplanted hemopoietic cells. AB - Evidence is reviewed to indicate that the conditioning regimens given to prepare the patient for bone marrow transplantation have two unintended but desirable consequences: (a) they eliminate endogenous progenitor cells that may otherwise be in competition with grafted hemopoietic progenitor cells, leaving all homing sites open for transplanted cells, and (b) they induce membrane alterations in marrow endothelium, thus effectively removing the endothelial barrier which otherwise the grafted cells must negotiate to enter the hemopoietic compartment of the marrow. Hence the conditioning regimens may also facilitate the homing of transplanted cells. PMID- 1515875 TI - Proliferation rates in epidermis of patients with graft-versus-host disease, non specific inflammation and normal skin. AB - There is evidence that epidermal stem cells or their early progeny may be the targets in graft-versus-host disease (GVHD). The early progeny should be a proliferating group of daughter cells more concentrated in areas just above or adjacent to stem cell regions. We have, therefore, compared proliferative rates of keratinocytes within relevant subregions of the epidermis using the AgNOR stain on biopsies from patients with GVHD, non-specific inflammatory infiltrates (NSI) and normal skin. We concurrently evaluated T cell infiltration using immunohistology on paraffin-embedded tissue with UCHL-1 antibody. Fifty-one bone marrow transplant patients were evaluated in each of three temporal groups (days 7-20 post-transplant, days 20-40 post-transplant, and days 80-100 post transplant). In each of these groups, 5-9 patients with a histological diagnosis of GVHD were compared to similar numbers of patients with a histological diagnosis of non-specific dermatitis.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1515876 TI - Autologous bone marrow transplantation in 22 adult patients with lymphoblastic lymphoma responsive to conventional dose chemotherapy. AB - In order to clarify the role of autologous bone marrow transplantation in adult lymphoblastic lymphoma (LBL) patients we have conducted a retrospective multi institutional Spanish survey. Twenty-two adult patients, 20 males, two females, age 14-52 years (median 25.5) with LBL were treated with high-dose chemoradiotherapy and autologous bone marrow support. Fourteen cases were transplanted in first complete remission (CR1) and eight with other chemosensitive status (four later CR, two partial remissions and two sensitive relapses). From the 14 cases transplanted in CR1, four had previous bone marrow involvement and one meningeal infiltration; eight cases were Ann-Arbor stage IV and fulfilled accepted high-risk criteria for relapse. The conditioning regimen consisted of cyclophosphamide (60 mg/kg x 2) and total body irradiation (9-12 Gy) in 16 cases and high dose chemotherapy in six. The procedure-related mortality was 9% (7% in CR1 patients). The actuarial 2-year overall survival for CR1 patients was 85% at a median follow-up of 19 months. Disease-free survival (DFS) was 77%. In patients with less favourable disease status the 2-year overall and DFS were 73% and 50% respectively. In this study the DFS in CR1 patients was not influenced by bone marrow involvement or high-risk criteria predictive for relapse. These results support the effectiveness of this procedure, mainly for patients in CR1. PMID- 1515877 TI - Marrow transplantation for treatment of multisystem progressive Langerhans cell histiocytosis. AB - Langerhans cell histiocytosis (LCH) embraces disorders characterized by the presence of marrow-derived abnormal Langerhans cells. A small number of patients with multisystem disease, vital organ dysfunction and rapid disease progression are considered to have a poor prognosis despite various treatments. Antiproliferative and immunosuppressive therapy, in combination with marrow transplantation, could be the appropriate treatment for these poor-prognostic patients. Four patients with progressive LCH were treated with high dose chemotherapy and fractionated total body irradiation followed by either an allogeneic (n = 2) or autologous (n = 2) marrow graft. Two of them are alive and have been disease free for almost 2 and 4 years after marrow grafting, respectively. One of the two survivors is the recipient of an allogeneic and the other of an autologous marrow graft. Two patients died, one of intrapulmonary hemorrhage 14 days after transplantation with active disease at autopsy, and the other of relapse of the original disease 355 days after marrow grafting. For patients with multisystem progressive LCH, allogeneic and autologous marrow transplantation may offer an opportunity for long-term remission and disease-free survival. PMID- 1515878 TI - Influence of the conditioning regimen on erythrocyte chimerism, graft-versus-host disease and relapse after allogeneic transplantation with lymphocyte depleted marrow. AB - Three different conditioning regimens were applied to 144 patients undergoing allogeneic bone marrow transplantation (BMT) with HLA identical sibling marrow, depleted of lymphocytes by counterflow centrifugation. All regimens consisted of cyclophosphamide and fractionated total body irradiation (TBI). In 49 patients treated with regimen A the total TBI dose was 9 Gy. In regimen B the dose rate of TBI was increased and anthracyclines were added (n = 65). Thirty patients received regimen C with a total TBI dose of 12 Gy but no anthracyclines. The different conditioning regimens did not influence the percentage of patients with detectable recipient CFU-GM prior to infusion of donor marrow. The incidences of mixed erythrocyte chimerism at 6 months after BMT were 73, 33 and 20% for regimens A, B and C respectively. The conditioning regimen influenced significantly mixed erythrocyte chimerism from 6 to 24 months after BMT. Both age and the conditioning regimen influenced significantly the incidence of acute graft-versus-host disease (GVHD) (p = 0.017 and 0.0001 respectively). Acute GVHD greater than or equal to I occurred in 15, 29 and 77% of the patients treated with regimens A, B and C respectively. The incidence of acute and chronic GVHD was significantly higher in complete donor chimeras than in mixed chimeras (p less than 0.001 and p less than 0.01). The probability of relapse was 43% in 32 and 18% in 43 good risk patients treated with regimens A and B respectively (p = 0.07). Longer follow-up is needed to draw conclusions about relapse in regimen C.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1515879 TI - Allogeneic bone marrow transplantation for Fanconi anemia. AB - Five patients (age range 7-14 years) received allogeneic bone marrow transplantation (BMT) for Fanconi anemia (FA). All patients showed progressive pancytopenia associated with congenital malformations. Diagnosis was confirmed by studies of cellular hypersensitivity to the clastogenic effect of the DNA crosslinking agent diepoxybutane. The conditioning regimen consisted of low dose cyclophosphamide (5 mg/kg x 4) and fractionated total body irradiation (167 cGy x 3). For graft-versus-host disease prophylaxis one patient was given cyclosporin alone while the remaining four patients received a combination of cyclosporin and two doses of methotrexate. Marrow was given unmanipulated from HLA-identical siblings. All patients are alive 18-67 months after grafting with Karnofsky scores of 100% and normal hemopoiesis of donor origin. Modifications in transplant protocols such as those here described have resulted in a decreased risk of severe transplant-related complications. These results confirm that BMT is a curative therapy in FA patients and should be considered as a first choice treatment if an HLA-identical donor is available. PMID- 1515880 TI - Pulmonary toxicity associated with high dose chemotherapy in the treatment of solid tumors with autologous marrow transplant: an analysis of four chemotherapy regimens. AB - We retrospectively reviewed the pulmonary toxicity of six high dose chemotherapy protocols using four chemotherapy regimens in the treatment of solid tumors. All protocols used either high dose cyclophosphamide or ifosfamide in combination with one to three additional chemotherapeutic agents. In each protocol autologous bone marrow was reinfused post chemotherapy to shorten the period of severe myelosuppression. Of 178 patients there were 20 cases of fatal or life threatening pulmonary toxicity including nine cases of pneumonia, nine cases of interstitial pneumonitis and two cases of pulmonary hemorrhage. Pulmonary function tests revealed modest changes in FEV1 and DLCO in the majority of patients, although 24 patients had more dramatic changes in DLCO suggesting interstitial damage. Significant decrements in FEV1 were seen in the BCNU containing regimen. Statistically significant or nearly significant decreases in DLCO were seen after all cyclophosphamide containing regimens. A regimen containing ifosfamide, carboplatin, and etoposide had minimal associated pulmonary toxicity. PMID- 1515881 TI - Pancreatitis associated with bone marrow transplantation in children. AB - Vomiting, abdominal pain and distension, common findings in children who receive bone marrow transplants (BMT), are usually attributed to chemo-irradiation and mucositis, universally found in these patients. We report seven children, 3.5% of BMT patients at our institutions, with these symptoms who were found to have mild to severe pancreatitis during conditioning for or after receiving BMT. All patients were receiving drugs known to cause pancreatitis, such as adrenocorticosteroids and sulfonamides as well as numerous putative pancreatotoxins such as cyclosporin A and cytosine arabinoside. Five of the seven patients had suffered from graft-versus-host disease. In patients who have received BMT, upper gastrointestinal symptoms should not be attributed to mucositis or chemo-irradiation without first testing for pancreatitis. PMID- 1515882 TI - Serum erythropoietin levels and blood component therapy after autologous bone marrow transplantation: implications for erythropoietin therapy in this setting. AB - To determine the potential impact of recombinant human erythropoietin (EPO) therapy in patients undergoing autologous bone marrow transplantation (BMT) and colony-stimulating factor therapy, we assayed endogenous serum EPO levels and noted blood transfusion requirements in relapsed non-Hodgkin's lymphoma patients treated with high-dose chemo-radiation therapy and autologous BMT. Hematocrit and reticulocyte counts were determined daily, and hematocrit was maintained in the 25-30% range by transfusion according to criteria established by our hospital transfusion committee. EPO levels were measured by radioimmunoassay and were determined at baseline, throughout therapy, and 2 and 3 months after BMT. Serum EPO levels increased more than 25-fold above baseline in most subjects after initiating chemoradiation therapy. No correlation was noted between serum EPO and hematocrit, reticulocyte count or serum creatinine. Total red blood cell units transfused ranged from 4 to 15 (mean 7.7). Mean total donor exposures (red blood cell plus platelet units transfused) were 83.6 units (range 16-175). Serum EPO levels increased early in the course of preparation for autologous BMT and remained elevated for at least 2-3 weeks thereafter although at a lower level. Red blood cell transfusions were required despite very high EPO levels after BMT. Red cell transfusions, moreover, accounted for only 9.2% (69 of 746) of total donor exposures and only 5.8% (42 of 746) of donor exposures during the interval when pharmacologic doses of erythropoietin might be of benefit. In contrast to the potential benefit of colony-stimulating factors such as G-CSF and GM-CSF in BMT, our study suggests limited value for erythropoietin therapy in this setting. PMID- 1515883 TI - Acute graft-versus-host disease following unrelated donor marrow transplantation: failure of conventional therapy. AB - The response to therapy of acute graft-versus-host disease (GVHD) is uncertain in recipients of unrelated donor (URD) bone marrow transplant (BMT). We analysed the outcome of treatment in 42 patients with moderate/severe acute GVHD. Initial therapy consisted of prednisone 60 mg/m2 orally daily for 7 days (n = 42), followed by anti-thymocyte globulin (ATG) 15 mg/kg i.v. twice daily for 8-10 doses after prednisone failure (n = 22). A clinical Stage Score for acute GVHD was determined initially and after 7, 14, 21, and 28 days of prednisone or ATG. Treatment failure represented worsening score after 7 days, involvement of a new organ or failure to improve after 14-28 days. Prednisone treatment led to 10 of 41 (24%) patients improving, while secondary therapy with ATG led to four of 21 (19%) improving. Of 42 patients treated, only nine (21%) achieved a complete and continuing response of acute GVHD by day +100. Neither age, diagnosis, recipient/donor gender status, histocompatibility nor GVHD prophylaxis regimen was associated with more frequent responses. Response to GVHD therapy was significantly correlated with survival at 100 days and 1 year post-BMT. We conclude that prednisone and ATG used for treatment of acute GVHD following URD BMT are associated with a high failure rate and that more aggressive therapy is warranted in these patients. PMID- 1515884 TI - Etoposide, cyclophosphamide and fractionated total body irradiation as a preparative regimen for marrow transplantation in patients with advanced hematological malignancies: a phase I study. AB - Thirty-seven patients with advanced hematologic malignancy were entered into a phase I study designed to define a maximum tolerable dose (MTD) of etoposide (VP 16) and cyclophosphamide (CY) combined with 12 Gy fractionated total body irradiation (TBI) as preparation for marrow transplantation from an HLA-identical sibling (n = 13) or with cryopreserved autologous marrow (n = 24). Dose levels ranged from 36 mg/kg of VP-16 combined with 67 mg/kg of CY to 52 mg/kg of VP-16 combined with 103 mg/kg of CY followed by 12 Gy TBI. The MTD for allogeneic marrow recipients was 36 mg/kg of VP-16 + 52 mg/kg of CY followed by 12 Gy TBI and for autologous marrow recipients 44 mg/kg of VP-16 + 103 mg/kg CY followed by 12 Gy TBI. Pulmonary and liver toxicities were dose limiting. All of 31 evaluable patients transplanted in relapse achieved a complete remission. However, in all but three of these patients the disease relapsed 28-899 (median 110) days post transplant. Currently, six of 24 autologous marrow recipients are surviving, three in remission 256, 340 and 764 days post-transplant. None of 12 allogeneic marrow recipients have survived. In conclusion, a preparative regimen combining 44 mg/kg of VP-16 + 103 mg/kg CY followed by 12 Gy TBI is well tolerated by autologous marrow recipients and 36 mg/kg VP-16 + 67 mg/kg CY followed by 12 Gy TBI is well tolerated by allogeneic marrow recipients.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1515885 TI - A modified harvest technique for cord blood hematopoietic stem cells. AB - Human umbilical cord blood is an excellent source of hematopoietic stem cells for research and bone marrow transplantation. We have developed a modified technique which effectively flushes and collects placental derived stem cells. Catheters were inserted into the umbilical artery and vein. Using this sterile and closed system technique, 10 saline diluted cord blood harvests had hematocrits of 16% to 25%, total mononuclear cell counts of 1.17 to 34.4 x 10(8) and volumes of 105-245 ml. The averaged extrapolated colony forming units from five cord blood harvests were as follows: CFU-GM 5.2 x 10(5) (9.96 x 10(4) to 1.24 x 10(6)), BFU-E 8.82 x 10(5) (2.40 x 10(4) to 1.61 x 10(6)) and CFU-GEMM 1.37 x 10(5) (7.33 x 10(3) to 3.18 x 10(5)). This quick technique avoids needle exposure and collects a significant volume of stem cells. PMID- 1515886 TI - Successful pregnancy after total body irradiation and bone marrow transplantation for acute leukaemia. AB - We report successful pregnancies in two young women (aged 24 and 20 years) following allogeneic bone marrow transplantation (BMT) for acute non lymphoblastic leukaemia. Conditioning therapy consisted of cyclophosphamide (120 mg/kg) and total body irradiation (TBI, 12 Gy) in 2 Gy fractions once daily for 6 days or twice daily for 3 days. Graft-versus-host disease prophylaxis was with methotrexate alone. Both women were amenorrhoeic after BMT and gonadal testing indicated hypergonadotrophic hypogonadism. Both women had normal pregnancies (2 years and 5 years after BMT) resulting in normal healthy infants. Previously successful pregnancy has been reported after TBI in three women in whom the TBI dose was less than 8 Gy. Our cases illustrate that normal outcome of pregnancy is possible at even higher doses of TBI. PMID- 1515887 TI - Is body weight a risk factor of interstitial pneumonitis after bone marrow transplantation? PMID- 1515888 TI - False positive diagnosis of pretransplant breast cancer in the bone marrow due to delayed fixation. PMID- 1515889 TI - A comparison of ultrasound exposure in therapy and pulsed Doppler fields. AB - A detailed comparison of the ultrasound exposure in water from a therapeutic beam and a pulsed Doppler beam was carried out. A significant overlap in acoustic power was found between therapy intensity levels used clinically and the upper end of the diagnostic range, between approximately 100 mW and 200 mW. In addition, pulse pressure amplitudes in the range 0.5-1.0 MPa were measured close to the transducer on both units. It is common to use physiotherapy equipment at pulse average intensities of 0.5 W/cm2 or less, and at these levels exposures of similar magnitude may be obtained with beams currently defined as therapeutic and those available from pulsed Doppler equipment. PMID- 1515890 TI - Proceedings of the British Medical Ultrasound Society, 23rd annual meeting. Bournemouth, December 10-12, 1991. Papers and abstracts. PMID- 1515891 TI - Routine radiographer screening for fetal abnormalities by ultrasound in an unselected low risk population. AB - A screening programme for fetal abnormalities began at The Hillingdon Hospital in July 1986. Second trimester ultrasound scans are performed by radiographers. A combined prospective and retrospective study of the ultrasound findings and outcome in all pregnancies delivered in 1989-1990 was undertaken. 6412 babies were born during this period, of whom 6183 (96%) were examined by ultrasound in the second trimester; 29 pregnancies were terminated for fetal abnormality. Of the 89 fetuses who were abnormal at birth or at induced termination of the pregnancy (1.4%), 84 were scanned in the second trimester. In 51 cases the abnormality was detected before 22 weeks gestation (sensitivity, 60.7%). 56 of these 84 abnormal fetuses scanned had potentially lethal or major handicapping abnormalities of which 41 were detected by ultrasound before 22 weeks gestation (sensitivity, 73%). There was one false positive diagnosis of abnormality which did not affect outcome. 6352 babies were normal at delivery or on discharge from hospital (specificity, 99.98%). PMID- 1515892 TI - A study of the relationship between routine ultrasound quality assurance parameters and subjective operator image assessment. AB - Comparisons have been made between a number of routine quality assurance (QA) measurements and a number of related subjective aspects of image quality. These comparisons between lateral resolution and perceived definition, dynamic range and subjective grey-level assessment, and slice thickness and overall image quality appraisal showed very poor correlation. We deduce from this that other QA parameters are needed to quantify good image quality as defined by the operators. PMID- 1515893 TI - A role for ultrasound in limb lengthening. AB - The distraction gap at eight sites in six patients undergoing limb lengthening was monitored by both standard radiographs and ultrasound. Using the measurements obtained we were able to assess the rate and quality of callus formation at the distraction site, something that radiographs alone do not enable one to do. We suggest that ultrasound has a valuable role to play in guaging the optimum rate of lengthening for a particular patient and commend it as a technique to complement radiographs in the follow-up of the increasing numbers of patients undergoing distraction osteogenesis. PMID- 1515894 TI - An audit of ultrasound diagnosis of gallbladder calculi. AB - Many series suggest that ultrasound is an accurate method for demonstrating cholelithiasis. However, these series were often prospective and the examinations performed by experienced sonographers. This audit addresses whether the accuracy is maintained in daily practice. We reviewed the ultrasound scans of 128 patients who underwent cholecystectomy for cholelithiasis and compared the findings. The operative and ultrasound findings were at variance in eight of the 128 patients (6.2%). Five were reported as having gallstones on ultrasound but none were found at cholecystectomy, a false positive rate for ultrasound of 3.9%. Three had abnormal gallbladders with no gallstones on ultrasound but gallstones were found at operation, a false negative rate of 2.3%. To avoid false positive diagnoses, suboptimal examinations should be repeated and the scan should be repeated immediately pre-operatively if only small calculi are seen. Alternative imaging should be performed if necessary, either cholescintigraphy in the acute situation or elective oral cholecystography. Some false negative examinations may be avoided by performing repeat examinations if the gallbladder is thick-walled and tender. With these provisos we conclude that ultrasound correctly diagnoses cholelithiasis in daily practice. PMID- 1515895 TI - The ultrasound appearances of intramural bowel gas: the bright ring appearance and the effervescent bowel. A report of three cases. AB - Bowel necrosis is a serious condition with a very high mortality rate. The earlier the diagnosis is made, the better chance for survival. Ultrasound is a primary imaging technique in the diagnosis of the acute abdomen. Three cases are presented in which bowel wall gas could be demonstrated on ultrasound. In all cases there was computed tomographic and either operative or post-mortem correlation. In each case there was a "bright ring" appearance of the affected bowel when the ultrasound examination was carried out in transverse section. In one case, small bubbles were seen arising from the deep surface of the bowel. PMID- 1515896 TI - The value of ultrasound in the assessment of bone. AB - The impenetrability of bone to ultrasound can be turned to advantage and the effects of bony lesions on the adjacent soft tissues can be analysed. Fractures, bone destruction, inflammation, distraction of bone and new bone formation can be diagnosed. PMID- 1515897 TI - Conventional 15 G needle technique for renal biopsy compared with ultrasound guided spring-loaded 18 G needle biopsy. AB - Two techniques for percutaneous renal biopsy were retrospectively reviewed to assess their relative safety and efficacy. Ultrasound localization of the kidney by a radiologists, with subsequent biopsy performed by a renal physician using a hand-held 15 G cutting needle (Tru-Cut), was compared with biopsy performed by a radiologist using an 18 G cutting needle with a spring-loaded biopsy device (Biopty) and real-time ultrasound guidance. The smaller needle with real-time ultrasound is more reliable at retrieving an adequate specimen for histological examination (93%) than the "conventional" technique (79%). Fewer complications occurred in the Biopty group although the difference did not reach statistical significance. The average length of stay in hospital was significantly shorter for elective biopsies with the Biopty device (1.80 compared with 2.93 nights, p less than 0.01). We recommend the use of the Biopty device with an 18 G needle and real-time ultrasound guidance as the method of choice for percutaneous renal biopsy. PMID- 1515898 TI - Two cases of isolated deficiency of all four limbs diagnosed antenatally with a review of the literature. PMID- 1515899 TI - Ultrasound demonstration of a leaking hydatid cyst of the liver causing "cyst within a cyst" appearance. PMID- 1515900 TI - The thread and streak sign of portal vein tumour thrombus demonstrated by colour Doppler imaging. PMID- 1515901 TI - Prenatal ultrasonographic diagnosis of an aneurysm of the vein of Galen. PMID- 1515902 TI - Epitheloid haemangioendothelioma of liver: a vascular tumour easily mistaken for metastatic carcinoma on ultrasound imaging. PMID- 1515903 TI - Opposite effects of prefrontal cortex and nucleus accumbens infusions of flupenthixol on stimulant-induced locomotion and brain stimulation reward. AB - Ventral tegmental area (VTA) stimulation produced conditioned place preferences for stimulation-paired environments the magnitudes of which were dose-dependently reduced by systemic application of the dopamine antagonist, haloperidol (0.0, 0.15, 0.3 mg/kg). Bilateral microinjections of cis-flupenthixol (FLU) into the nucleus accumbens (0.0, 1.0, 5.0 or 10.0 micrograms) also resulted in reductions in the size of stimulation-induced place preferences as well as reductions in the magnitude of the hyperlocomotor response to 1.5 mg/kg (s.c.) D-amphetamine. Comparable microinjections of FLU into the medial prefrontal cortex (PFC) produced diametrically opposite effects: the size of VTA stimulation-induced place preferences was either unaffected (1.0 and 5.0 microgram groups) or slightly increased (10 micrograms group) and amphetamine-stimulated hyperlocomotion was dose-dependently potentiated. These behavioral findings suggest a dopamine-mediated modulatory role for the PFC over reward relevant elements within the nucleus accumbens. PMID- 1515904 TI - Expression, but failing maturation of procholecystokinin in cerebellum. AB - The cerebellum is the only region of the central nervous system which has been found to be devoid of cholecystokinin (CCK). The assays used, however, have been directed against the alpha-amidated C-terminus of fully processed CCK peptides. Using Northern blot analysis and a library of radioimmunoassays specific for different sequences of proCCK in combination with chromatography and enzyme cleavage, we have now examined the expression and processing of proCCK in fetal, neonatal and adult cerebellar tissue from man, pig and rat. In rat cerebellum CCK mRNA was present already in the fetal state. Two weeks after birth the concentrations declined. Also proCCK was found in significant concentrations in the fetal human and rat cerebellum (approximately 20 pmol/g); but already before birth the expression began to decrease towards low concentrations in adults. The adult porcine cerebellum contained 3.2 pmol proCCK and glycine-extended processing intermediates per gram (range less than 0.1-10.4 pmol/g), and 0.8 pmol carboxyamidated CCK per gram (range 0.1-4.1 pmol/g) varying in size from CCK-58 to CCK-5. For comparison, the adult porcine cerebral cortex contained 757 pmol carboxyamidated CCK/g, 20 pmol glycine-extended CCK/g and no proCCK. We conclude that cerebellum expresses proCCK with the highest level of expression in fetal life. In comparison with other regions of the brain, the maturation to transmitter-active, carboxyamidated CCK peptides is, however, attenuated in both fetal and adult cerebellar tissue. PMID- 1515905 TI - Tonic descending modulation of spinal neurons with renal input. AB - Experiments were conducted to determine the influence of tonically active descending pathways on thoracolumbar spinal neurons that respond to renal nerve stimulation in anesthetized cats. We examined the effect of reversible blockade of spinal conduction on spontaneous activity, responses to renal nerve stimulation and responses to somatic stimuli of 71 spinal neurons. Mid-thoracic cold block resulted in enhanced responses (tonically inhibited neurons), reduced responses (tonically excited neurons), or did not affect neuronal responses. The spontaneous activity of 47 of 69 neurons (68%) increased from 7.3 +/- 2.0 spikes/s before cooling to 23.3 +/- 4.5 spikes/s during cooling. Activity of 8 neurons (12%) decreased while 14 (20%) had no change in activity. Cooling increased the responses of 51 of 71 neurons (72%) to renal nerve stimulation. Renal nerve stimulation evoked a two-fold increase in both short latency (early) and long latency (late) responses. Four neurons had a late response which was revealed by cold block. Cooling decreased responses of 8 of 71 neurons (11%) and 9 neurons (13%) were not affected. Cooling increased the early responses but decreased the late responses of 3 of 71 neurons (4%). All neurons had somatic receptive fields and 33 of 56 exhibited increased responses to somatic stimulation during cooling. In addition, receptive field sizes of 26 neurons increased. Four neurons had a decrease and 25 neurons had no change in receptive field size during cooling. These data indicate that tonically active descending pathways modulate the activity of most spinal neurons with renal input and the major effect of these pathways is inhibitory. This influence may be important in the modulation of spinal circuits that participate in reflexes evoked by renal afferent fibers. PMID- 1515906 TI - Selective inhibition of glial cell metabolism in vivo by fluorocitrate. AB - The effect of fluorocitrate on glial and neuronal amino acid metabolism was studied. One nmol of fluorocitrate administered intrastriatally in the rat caused a 95% reduction of glutamine formation from [14C]acetate, a substrate which enters the glial cells selectively. The metabolism of [14C]glucose which enters neurons, was unaffected by fluorocitrate treatment except for the glutamine formation. This is evidence that fluorocitrate is a selective inhibitor of the glial Krebs' cycle. [14C]Citrate and 2-oxoglutarate labelled amino acids in a manner similar to [14C]acetate, which shows that these substrates are taken up and metabolized by glial cells. Differences in the labelling of gamma aminobutyric acid (GABA) from [14C]acetate and citrate suggest that astrocytes associated with GABAergic and glutamatergic nerve terminals may differ in their preference for amino acid precursors. PMID- 1515907 TI - Estrogen fails to reduce tuberoinfundibular dopaminergic neuronal activity and to cause a prolactin surge in lactating, ovariectomized rats. AB - The activity of tuberoinfundibular dopaminergic (TIDA) neurons was estimated by measuring the concentrations of dihydroxyphenylacetic acid (DOPAC) in the median eminence of ovariectomized lactating rats, ovariectomized non-lactating female rats and castrated male rats in correlation with the estrogen-induced prolactin (PRL) surge. PRL surge with a peak at 17.00 h was observed in ovariectomized non lactating rats but not in the other groups. DOPAC levels were significantly lower at 17.00 h than at 11.00 h in non-lactating female rats, but there was no change of DOPAC levels in lactating rats and male rats. These results indicate that TIDA neuronal activity is inhibited at the time of estrogen-induced PRL surge and that the TIDA neurons may alter their function to result in refractoriness of PRL response to estrogen in the lactating rat. PMID- 1515908 TI - Lateral dominance and motor unit firing behavior. AB - Twelve subjects were classified as left-handed (LH) or right-handed (RH) using Annett's hand dominance classification. Motor unit recordings were obtained from the first dorsal interosseous (FDI) muscle of each hand using a quadrifilar needle electrode. Firing occurrences of individual motor units were then identified and the firing rates of all motor units recorded during the contraction were cross-correlated. The results demonstrated significantly greater firing rate cross-correlation scores in the dominant hand than in the non dominant hand for both LH and RH subjects. This association between hand dominance and the common drive of motor unit firing rates lends credence to the idea that one or more CNS sites may influence conjoint motor unit firing behavior. PMID- 1515909 TI - A cocaine analog and a GBR analog label the same protein in rat striatal membranes. AB - Because some evidence suggests that cocaine and GBR12935 bind to different sites, we utilized photoaffinity probes from both classes of compounds to see if they label the same protein. [125I]RTI-82 a cocaine analog, and [125I]DEEP, a GBR analog, labeled protein(s) showing the same molecular weight, a similar pharmacological profile and a similar sensitivity to neuraminidase. PMID- 1515910 TI - Ectopic axonal firing in an epileptic cortical focus is not triggered by thalamocortical volleys during the interictal stage. AB - The triggering of ectopic action potentials (APs) at axon terminals in a chronic epileptic cobalt focus was investigated in thalamocortical (TC) neurons of rats under urethane anesthesia. TC cells which were in register with an active epileptic aggregate discharged bursts of 2-11 APs. According to the rules of the collision test, we ascertained that bursts contained APs of ectopic and/or somatic origin. During a transient blockage of TC orthodromic discharges produced by raising the extracellular concentration of Mg2+, ectopic bursts which were in close time relationship with the focal interictal electrocorticographic spikes persisted. These results demonstrate (i) the antidromic nature of identified ectopic APs and (ii) that, during the interictal stage, such axonal APs were not a consequence of TC discharges. The possible mechanisms for the triggering of ectopic axonal APs in the chronic cobalt focus are discussed. PMID- 1515912 TI - Recovery in hemiparkinsonian rats following intrastriatal implantation of activated leukocytes. AB - Behavioral improvement has been seen in hemiparkinsonian animals after surgical lesions of the denervated caudate nucleus. This study was designed to investigate the role of inflammatory cells in injury-induced recovery. A hemiparkinsonian syndrome was induced in rats by unilateral injections of 6-hydroxydopamine into the pars compacta of the substantia nigra. Phytohemagglutinin-stimulated rat peritoneal cells, predominantly T cells and macrophages, were stereotactically implanted in the lesioned caudate-putamen, and amphetamine-induced turning was used to assess recovery. Animals receiving implants of activated peritoneal cells showed a 47% decrease in amphetamine-induced turning 8 weeks after implantation, which was not seen in control or sham-operated animals. Immunocytochemistry revealed increased tyrosine hydroxylase reactive fibers in the leukocyte implanted striatum. We conclude that implantation of activated leukocytes promotes functional recovery in hemiparkinsonian rats. PMID- 1515911 TI - Cellular variations in estrogen receptor mRNA translation in the developing brain: evidence from combined [125I]estrogen autoradiography and non-isotopic in situ hybridization histochemistry. AB - The spatial distribution of cells in the adult rodent forebrain which express estrogen receptor mRNA, as shown by in situ hybridization histochemistry with isotopically-labeled probes, has been reported to overlap with regions that are known targets of estrogen and which bind estrogen. The extent to which detection of estrogen receptor mRNA within developing forebrain neurons of the postnatal day 10-12 female rat is accompanied by translation into estrogen binding sites was investigated by combining [125I]estrogen autoradiography with non-isotopic (digoxigenin) in situ hybridization, using a 48-base oligodeoxyribonucleotide probe encoding a sequence of the estrogen-binding domain of rat uterine estrogen receptor cDNA. Estrogen receptor mRNA and estrogen binding sites appeared to be restricted to neurons. No mRNA or binding was seen in ependymal cells. Cells expressing estrogen receptor mRNA were widely distributed in the developing rat forebrain and were found in brain regions generally corresponding to those previously shown in the adult, with the addition of some regions not previously described, such as the medial habenula and dorsal endopiriform nucleus. Although there was widespread overlapping of estrogen receptor mRNA expression with known estrogen binding sites, there were regional and cellular variations in the extent of receptor mRNA translation. This pattern was true for developing forebrain regions previously defined as estrogen receptor-containing (hypothalamus, preoptic area, medial and lateral septum, vertical and horizontal nuclei of the diagonal band, cerebral cortex, hippocampus and amygdala) as well as for regions heretofore not considered estrogen targets (the thalamus, dorsal endopiriform nucleus, claustrum, ventral pallidum/substantia innominata and the basal nucleus of Meynert) or characterized as estrogen-responsive in the adult without previously documented estrogen binding [caudate-putamen (striatum)]. While estrogen binding and receptor mRNA expression always co-localized, neurons expressing estrogen receptor mRNA did not always exhibit ligand binding and there was no clear-cut relationship between the intensity of the hybridization signal and estrogen binding. Little, however, is known about translational control of estrogen receptor expression in the brain. Localization of estrogen binding sites to regions not generally considered targets of estrogen would appear to reflect the greater sensitivity of the iodinated ligand than the tritiated estrogens more commonly used for autoradiography. Non-isotopic in situ hybridization histochemistry combined with [125I]estrogen autoradiography represents a very powerful tool with which to study regulation of estrogen receptor gene expression at the single cell level with an exceptional degree of cellular and anatomical resolution.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1515913 TI - Messenger RNAs encoding glutamate-decarboxylases are differentially affected by nigrostriatal lesions in subpopulations of striatal neurons. AB - Dopaminergic nigrostriatal neurons constitute one of the major inputs to the striatum, and play a role in the regulation of gamma-aminobutyric acid (GABA) and glutamic acid decarboxylase (GAD), the GABA-synthesizing enzyme, in striatal neurons. The effect of nigrostriatal lesions on the level of expression of messenger RNAs encoding two distinct isoforms of glutamate decarboxylase was examined at the single cell level with in situ hybridization histochemistry. Rats received a unilateral injection of the neurotoxin 6-hydroxydopamine in the substantia nigra and were sacrificed 2 or 3 weeks later. Sections of the striatum were processed for in situ hybridization histochemistry with radiolabeled RNA probes selective for mRNAs encoding glutamate decarboxylase with molecular weights of 65,000 and 67,000, respectively. In addition, immunohistochemistry with a monospecific antibody for the latter glutamate decarboxylase isoform was performed. In agreement with previous reports, we observed increased labeling for the messenger RNA encoding glutamate decarboxylase (M(r) 67,000) in a population of medium-sized striatal efferent neurons normally expressing low levels of this messenger RNA. We now show that this effect occurred in two striatal compartments, the striosomes and the extrastriosomal matrix, and was accompanied by increased immunostaining for the corresponding protein with a monospecific antibody. In contrast, labeling for messenger RNA encoding GAD (M(r) 67,000) was decreased in a population of medium-sized neurons normally expressing high levels of this messenger RNA and corresponding to GABAergic interneurons. Labeling for messenger RNA encoding glutamate decarboxylase (M(r) 65,000) was not modified in the dopamine-depleted striatum. The results show that dopamine depletion differentially affects gene expression for different isoforms of glutamate decarboxylase in distinct subpopulations of striatal neurons in rat. PMID- 1515914 TI - Halothane-induced hyperpolarization and depression of postsynaptic potentials of guinea pig thalamic neurons in vitro. AB - Intralaminar thalamic nuclei have been considered to be a component of the non specific sensory system which is involved in physiological functions related to consciousness and pain sensation. The effect of halothane on membrane potentials and synaptic properties of neurons of the parafascicular (Pf) nucleus in guinea pig brain slices was investigated using intracellular recording methods. Halothane at concentrations of 0.4-1.0 mM, which are in the range of clinical concentrations, produced hyperpolarizations of 2-8 mV in approximately 50% of the cells. The halothane-induced hyperpolarization was nullified at a membrane potential close to the K+ equilibrium potential. The amplitude of the hyperpolarization was dependent on the external K+ concentration, and was decreased by either Ba2+, or 4-aminopyridine, or intracellular injection of Cs+. All these results indicate that the hyperpolarization was due to an increase in K+ conductance. Halothane at clinical concentrations depressed both excitatory and inhibitory postsynaptic potentials in a concentration-dependent manner. On the other hand hyperpolarizing responses to exogenous gamma-aminobutyric acid (GABA) in the presence of bicuculline were suppressed by halothane, but depolarizing responses to L-glutamate were not altered. The results indicate that the depressant action of the anesthetic on the excitatory postsynaptic potential (EPSP) may occur presynaptically, whereas the blocking action on the inhibitory postsynaptic potential (IPSP) may occur postsynaptically. PMID- 1515915 TI - Properties of depolarizing bipolar cell responses to central illumination in salamander retinal slices. AB - The voltage and current responses of depolarizing bipolar cells to central illumination were studied by means of whole-cell recording in retinal slices of the larval tiger salamander, Ambystoma tigrinum. To stabilize the responses, it was necessary to limit exchanges between the cytosol and the solution in the patch pipette by reducing the diameter of the pipette tip opening. The current voltage relationship of the cell membrane in darkness displayed a strong outward rectification, and the inward current evoked by light could be consistently reversed by depolarization only when tetraethylammonium was added to the pipette solution. As a result of the membrane non-linearity, increases in the intensity of bright lights caused relatively smaller amplitude increases in the voltage than in the current responses and the latter had a proportionally smaller after effect. With larger pipette tip openings, the cytosol equilibrated with the pipette filling solution. Under these conditions the light-evoked responses gradually became slower and acquired an on-off pattern, their final amplitude and polarity being determined by the ratio of the chloride concentrations on each side of the cell membrane. This finding is interpreted as revealing the existence of two response components: a chloride-dependent on-off increase in conductance and a faster depolarizing input that was lost through diffusional exchange. Addition of GTP and ATP to the electrode filling solution had a stabilizing effect on the labile component, whether or not cyclic GMP was also included. Observations on the magnitude of the conductance changes and on diphasic reversals indicate that the labile response component, presumably representing direct input from photoreceptors, is caused by an increase in conductance. The resulting inward current was still present at a low intracellular chloride concentration and may be assumed, therefore, to be carried by a cation influx. PMID- 1515916 TI - Localization and characterization of diazepam-binding inhibitor (DBI)-like peptides in the brain and pituitary of the trout (Salmo gairdneri). AB - The distribution of diazepam-binding inhibitor (DBI)-like peptide(s) in the brain and pituitary of the trout was determined by the indirect immunofluorescence technique using an antiserum raised against synthetic rat octadecaneuropeptide (ODN). Numerous immunoreactive perikarya and processes were observed in the basal hypothalamus, within the pars lateralis of the nucleus lateralis tuberis. In the pituitary, ODN-immunoreactive processes were visualized in the neurohypophysial tract, projecting into the pars intermedia, and the pars distalis. Reverse-phase high-performance liquid chromatography combined to radioimmunoassay quantification was used to characterize the DBI-related material in tissue extracts. In both pituitary and hypothalamic extracts, the major immunoreactive form eluted with a retention time higher than that of rat ODN. In the hypothalamus, a minor peak co-eluting with the synthetic ODN standard was also resolved. The existence of peptides related to mammalian DBI in the hypothalamo hypophysial complex of the trout suggests these neuropeptides may participate in the control of pituitary hormone release. PMID- 1515917 TI - Acetylcarnitine, carnitine and glucose diminish the effect of muscarinic antagonist quinuclidinyl benzilate on striatal acetylcholine content. AB - The content of acetylcholine (ACh) in the striatum, brain cortex and hippocampus of rats was lowered 20-180 min after intraperitoneal injection of the muscarinic antagonist quinuclidinyl benzilate (QNB). The depletion of ACh content in the striatum was diminished in animals treated with a single dose of acetyl-L carnitine, L- or D,L-carnitine, or D-glucose. It is likely that QNB stimulates ACh release by blocking presynaptic muscarinic autoreceptors and that acetylcarnitine, carnitine and glucose support the resynthesis of ACh by increasing the availability of acetylcoenzyme A. They do not have the same consistent effect in the brain cortex and hippocampus; this difference may be related to the lower turnover rate of ACh and to the difference in the anatomical arrangement of cholinergic structures in these parts of the brain. PMID- 1515918 TI - Effects of lesions of the optic nerve, optic tectum and nervus terminalis on rod precursor proliferation in the goldfish retina. AB - Teleost retinas grow throughout life by proliferation of neuroblasts at the retinal margin and dedicated rod precursors in the outer nuclear layer. Mechanisms regulating this proliferation are largely unknown. Previous investigators observed that rod precursor replication, as detected by incorporation of radioactive thymidine into cells of the outer nuclear layer, is enhanced after optic nerve crush. We attempted to determine whether this was due to severing of the retinopetal (nervus terminalis, n.t.) or retinofugal (retinal ganglion cell) axons in the optic nerve of the goldfish, Carassius auratus. In the first series of experiments, we ablated unilaterally the optic nerve, olfactory bulb (containing n.t. ganglia), or optic tectum (containing retinal ganglion cell axons and n.t. collaterals). Rod precursor proliferation increased dramatically in both retinas as soon as 5 days after surgery; in addition, the numbers of dividing cells were greater in the ipsilateral retina 10-15 days after optic nerve crush or tectal ablation and in the contralateral retina 20-25 days after olfactory bulb ablation. These observations are not accounted for by the known projections of retinal ganglion cells, but are consistent with the projections of the n.t. In the second series of experiments, n.t. projections to the brain and retina were severed bilaterally 7-8 weeks before the unilateral optic nerve crush or hemitectal ablation. Rod precursor proliferation increased as before, but the quantities of dividing cells were always equal in both retinas. We conclude that the n.t. may modulate rod proliferation locally and that injury to (some) brain regions may cause release of mitogens that affect rod precursors in both retinas. PMID- 1515919 TI - Does the release of vasopressin within the supraoptic nucleus of the rat brain depend upon changes in osmolality and Ca2+/K+? AB - Microdialysis in conjunction with a highly sensitive radioimmunoassay was used to monitor the in vivo release of arginine vasopressin (AVP) within the supraoptic nucleus (SON) of the rat brain (n = 70). Thirty-min dialysates were collected in urethane-anesthetized animals before, during and after hypertonic or hypotonic pulses were delivered via the probe. As compared to artificial cerebrospinal fluid (aCSF)-perfused controls, 1M aCSF given over a period of 210 min resulted in an increased intranuclear AVP release which, however, reached its peak only in the post-stimulation period, i.e. after replacement of hypertonic with isotonic aCSF again (rebound phenomenon). Hypertonic (0.5 M, 1 M or 2 M) pulses given 150 min after the first (1 M) pulse resulted in 3 different rebound responses: a marked decrease (to 25.3%, P less than 0.001), no change or slight increase (132%, n.s.). As shown by the response to correction of the hypertonicity to normal as well as by perfusion of hypotonic aCSF (0.01 M), release of AVP within the SON appears more responsive to a reduction than to an elevation in the osmolality of aCSF. Omission of Ca2+ from and addition of EGTA to the aCSF decreased the osmotically stimulated, but not the basal AVP release. If K(+) hypertonic aCSF was used, however, basal AVP levels increased significantly; in contrast, the rebound increase failed to differ from aCSF-perfused controls. It is concluded from these findings that release of AVP from intact neuronal structures in the SON is responsive to changes in osmolality with an apparent greater sensitivity to decrease in osmolality. PMID- 1515920 TI - Medullary expiratory neurons in the decerebrate rat: an intracellular study. AB - Intracellular recordings and labelings with horseradish peroxidase (HRP) of expiratory (E) neurons were performed in decerebrate, paralyzed, and ventilated rats. A total of 37 neurons were recorded, from which 4 cells and 1 axon were labeled. They were located in two regions of the ventrolateral medulla. One was in the rostral portion of the nucleus ambiguus just caudal to the facial nucleus, and the other in the nucleus retroambiguus at the level of the caudal medulla. These expiratory neurons had rhythmical changes in membrane potential similar to those reported in cat, i.e., a depolarization in the intervals between phrenic bursts which evolved in an augmenting (E-aug, n = 15), or bell-shaped or 'plateau' (E-all, n = 22) pattern until a rapid hyperpolarization at the start of inspiration. Both types were hyperpolarized during inspiration by chloride dependent, inhibitory postsynaptic potentials (IPSPs) which were demonstrated in 17 neurons (10 E-aug and 7 E-all) from which reversal was obtained. Such IPSPs also existed during post-inspiration (stage I of expiration) in 4 of the 10 augmenting E neurons. They were identified by antidromic stimulation or HRP labeling, or both, as bulbospinal neurons (n = 2), cranial motoneurons (n = 4), or not antidromically activated (NAA) neurons (n = 31). All the identified bulbospinal neurons and the motoneurons exhibited an E-all pattern. The expiratory neurons of the caudal medulla had various projections as demonstrated with HRP labeling: one bulbospinal neuron with ipsilateral axon giving off intramedullary collaterals, and NAA neurons with rostral medullary projections or with axons crossing the midline.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1515921 TI - Effect of superior colliculus lesions on sensory unit responses in the intralaminar thalamus of the rat. AB - The effects of kainic acid lesions of the intermediate and deep layers of the superior colliculus on the sensory input to the intralaminar thalamus of the rat were determined. Ipsiversive circling and contralateral sensory neglect were consistently seen after lesion placement. Two to 7 days later, the intralaminar thalamus was systematically explored for extracellular mechanoreceptive unit responses to high threshold and low threshold stimuli. On the side ipsilateral to the lesion the number of responsive units was reduced by 51%. The loss was particularly marked for nociceptive units (80%), and low threshold and complex units with orofacial receptive fields (73%). This effect may involve a partial deafferentation of the intralaminar thalamus as well as altered excitatory thresholds of thalamic neurons. It is suggested that the functionally distinct direct tectothalamic projection as well as the indirect tecto-reticulo-thalamic pathway are implicated. PMID- 1515922 TI - Effects of PVN lesions on the responsiveness of female rats to estradiol. AB - Previous research has shown that the paraventricular nucleus of the hypothalamus (PVN) is an important site of action for the effects of estradiol on feeding behavior. The recent finding that estrogenic stimulation of the PVN lowers food intake without inducing lordosis suggests that the effects of estradiol on feeding and sexual behaviors are organized separately within the brain. Whether the effects of estradiol on food intake can be attenuated by PVN lesions is therefore a question of practical and theoretical interest. In this experiment we examined the behavioral responsiveness of females with PVN lesions to peripheral treatment with estradiol. 32 adult, female rats received either bilateral or sham lesions of the PVN. All subjects were ovariectomized 2 weeks after the lesion. 2 Weeks following ovariectomy, half of the animals were injected with 2 micrograms of estradiol benzoate (EB) for 3 days, and half were injected with the oil vehicle. 10 days later, the treatment conditions for each subject (oil or EB) were reversed. Histological analysis indicated that 9 females had bilateral lesions of the PVN and 4 had bilateral lesions of the dorsomedial nucleus of the hypothalamus (DMN); 11 animals received sham lesions. Compared with oil treatment, EB injections significantly lowered water intake and body weight gain in all groups. However, food intake was suppressed in the DMN and sham but not in PVN-lesioned females. In addition, statistical analyses indicated that EB treatment induced similar levels of female sexual behavior in all groups. Thus, PVN lesions did not interfere with the ability of estradiol to stimulate lordosis.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1515923 TI - Synaptic associations between oxytocin-containing magnocellular neurons and neurons containing corticotropin-releasing factor in the rat magnocellular paraventricular nucleus. AB - In the paraventricular nucleus (PVN) of the rat hypothalamus, we determined synaptic associations between oxytocin (OXT)-containing magnocellular neurons and parvocellular neurons containing corticotropin-releasing factor (CRF) by using a double immunolabeling technique in 7 animals. In single vibratome sections of the hypothalamus, immunoreactive CRF and OXT were labeled with silver-gold particles and diaminobenzidine (DAB) chromogen, respectively. By light microscopy CRF containing fibers appeared to be black dots, some of which encircled magnocellular perikarya labeled with brown DAB chromogen in the PVN. By electron microscopy we discriminated OXT neurons having fine DAB-chromogen particles distributed throughout the cytoplasm and on large secretory granules from CRF neurons having dense coarse particles of silver-gold. Occasional CRF axons terminated on perikarya or dendritic processes of OXT neurons, making synaptic contacts. The terminals which were characterized by having clusters of small clear vesicles and a few dense core vesicles showed equal thickenings of pre- and postsynaptic membranes at the synaptic junctions. PMID- 1515924 TI - Temperature sensitivity of thin unmyelinated fibers in rat hippocampal cortex. AB - The effect of changes in temperature on the activity of thin intracortical unmyelinated fibers was investigated in rat hippocampal slices. The amplitude of the presynaptic volley was increased by 40% when the temperature was raised from 23 degrees C to 30 degrees C, whereas the area of the presynaptic volley was reduced. Increasing the temperature above 30 degrees C was without further effect on the amplitude. The conduction velocity was 0.3 m.s-1 at 35 degrees C and 0.1 m.s-1 at 12 degrees C. The Q10 of velocity (25 degrees C-35 degrees C) was 1.6. PMID- 1515925 TI - Terminal distribution of mossy fibers traversing the superior cerebellar peduncle in the mouse. AB - The carbocyanine membrane probe DiI was applied to cut fibers of the superior cerebellar peduncle in the fixed brains of adult mice. Labeled mossy fibers in the cerebellar cortex formed rosettes only in the most superficial aspect of the granular layer, just beneath the Purkinje cell layer. These results provide evidence for a functional division of the cerebellar granular layer into horizontal laminae, in addition to the commonly recognized lobular and sagittal divisions of the cerebellar cortex. PMID- 1515926 TI - Decrement of muscarinic receptor-stimulated low-KM GTPase in striatum and hippocampus from the aged rat. AB - Previous studies have shown that there is an age-related loss of responsiveness in several different receptor systems (e.g. beta-adrenergic, dopaminergic and muscarinic). Our research, using perifused striatal slices and examining muscarinic agonist enhancement of K(+)-evoked dopamine release, has determined that at least part of the loss of sensitivity in muscarinic receptors (mAChR) may occur early in the post-receptor signal transduction process. The present study was carried out to further characterize and localize this deficit by examining carbachol- and oxotremorine-stimulated low-KM guanosine triphosphatase (GTPase) activity in striatal as well as hippocampal tissue obtained from adult (6 months) and old (24 months) Wistar rats. Receptor stimulated low-KM GTPase catalyzes the conversion of GTP to GDP to end the signal transduction cycle and is an indicator of receptor-G-protein coupling/uncoupling. The results showed that stimulated GTPase activity was significantly reduced in hippocampal and striatal tissue from the old animals. These findings suggest that there may be an age-related coupling/uncoupling deficit between muscarinic receptor and G-proteins, and that this deficit may contribute to the reduced mAChR responsiveness in senescence. PMID- 1515927 TI - Neuropeptide Y-like immunoreactive neurons in the suprachiasmatic subparaventricular region in the hedgehog-tenrec. AB - The distribution of the neuropeptide Y (NPY) was studied in geniculate and peri chiasmatic regions in the lesser hedgehog-tenrec, Echinops telfairi (Insectivora). Only few neurons demonstrated NPY-like immunoreactivity in the ventral lateral geniculate nucleus. In contrast, NPY-immunoreactive perikarya were clearly present in the suprachiasmatic nucleus (SCh) and dorsal and caudal to it. The latter region might correspond to the subparaventricular zone (SPV), recently identified in the rat as an additional area involved in processing circadian rhythms. While the distribution of a distinct cell population across nuclear boundries in both SCh and SPV might conform to the present idea of processing circadian rhythms, the presence of NPY-like immunoreactive neurons in these areas is rather unusual. In mammals, such neurons have only been demonstrated so far in the mentioned insectivore as well as in man. PMID- 1515928 TI - Muscle lactate dehydrogenase activity is decreased in murine motor neuron disease. AB - Lactic dehydrogenase (LDH) activity was examined in affected skeletal muscles of the wobbler mouse, a murine model in which denervation follows degeneration of spinal cord motoneurons. Average biceps brachii LDH activity was reduced at 7 and 15 but not at 3 postnatal weeks. These results demonstrate a progressive alteration in muscle energy metabolism in a natural model of motor neuron disease. PMID- 1515929 TI - Effects of a non-peptide angiotensin receptor antagonist on drinking and blood pressure responses to centrally administered angiotensins in the rat. AB - Both angiotensin II (ANG II) and angiotensin III (ANG III) administered centrally produce drinking and increases in blood pressure. The recent characterization of two subtypes for the ANG II receptor, the AT1 and AT2, raises the questions of whether drinking and pressor responses to ANG II can be separated pharmacologically and whether ANG III acts via the same receptor subtype. Therefore, the current study examined drinking and blood pressure responses to ANG II and ANG III administered centrally in adult male Sprague-Dawley rats in the presence or absence of a selective AT1 receptor antagonist. Blockade of the AT1 receptor abolished both drinking and pressor responses to ANG II and ANG III. However, drinking to the cholinergic agonist, carbachol, was unaffected. These results demonstrate that centrally administered ANG II and ANG III increase both water intake and blood pressure via the AT1 receptor subtype. PMID- 1515930 TI - Networks formed by dorsal root ganglion neurites within spinal cord explants: a computer-aided analysis of HRP intracellularly labeled neurons. AB - Dorsal root ganglion (DRG) neurons from rat embryos were explanted either alone or with the attached spinal cord (SC). Neuritic processes were mapped out histologically using an intracellular iontophoretic HRP method. Computer reconstructions and morphometric parameters allowed a comparative quantitative analysis of the DRG neurons and of their neuritic processes in both models. The first model, strongly dependent on nerve growth factor (NGF) for its survival, developed large multidirectional processes. The second model showed a bipolar distribution of its neuritic processes, the central one entering predominantly the dorsolateral part of the cord explant and ramifying both homo- and heterolaterally. The quantitative data revealed a significant decrease in the overall size of the neuritic networks of the second model (with attached SC). A discriminant analysis permitted the recognition of these two populations of DRG neurons. The role of the spinal cord explant, and more precisely the target cells of the dorsal horn, was considered to be a prominent factor in the development of the DRG neuritic networks. PMID- 1515931 TI - Evidence for a common network of brain structures involved in parkinsonian tremor and voluntary repetitive movement. AB - Repeated measurements of regional cerebral blood flow (rCBF) were obtained in 7 patients who underwent a stereotactic thalamic electrode implantation in the nucleus ventralis intermedius (nVIM) of the thalamus for severe hemi-parkinsonian tremor. Using positron emission tomography and oxygen-15 labelled water, rCBF was studied in each patient in two conditions: in absence of tremor, e.g. under nVIM electrical stimulation, and in presence of tremor. X-ray tomograms permitted individual definition of anatomical regions of interest. In presence of tremor, normalized rCBF increases were observed in the following regions: postcentral (13.6 +/- 8.4%, P = 0.0003), precentral (7.7 +/- 8.8%, P = 0.016), paracentral (7.7 +/- 8.4%), supplementary motor (8.2 +/- 10.4%, P = 0.025), caudate nucleus (5.7 +/- 7.6%, P = 0.03), vermis (9.7 +/- 7.3%, P = 0.007), cerebellar grey nuclei (9 +/- 6%, P = 0.016) on the electrode side and on the contralateral vermis (17.8 +/- 7.5%, P = 0.0003) and cerebellar grey nuclei (22 +/- 6.3%, P = 0.0004). These results clearly indicate an activation of the sensory-motor cortex, as well as an involvement of the supplementary motor area and the cortico cerebellar pathways in Parkinsonian resting tremor (PRT). They demonstrate that PRT shares common network of brain structures with repetitive voluntary movement. PMID- 1515932 TI - Uptake of 3-hydroxykynurenine measured in rat brain slices and in a neuronal cell line. AB - The uptake of 3-hydroxykynurenine (3HK), a tryptophan metabolite with reported convulsant and cytotoxic properties, has been investigated in a neuronally derived hybrid cell line and in tissue slices prepared from rat brain. In both systems, the observed uptake was temperature-dependent and inhibited in the presence of large neutral amino acids. The apparent Km and Vmax determined for 3HK uptake into N18-RE-105 cells were 1.65 mM and 25.5 nmol/(min x mg protein), respectively. The uptake of 3HK into rat brain slices could be resolved into two components on the basis of their requirements for sodium. Kinetic analyses performed using hippocampal slices revealed a Km of 1.1 mM and Vmax of 18.8 nmol/(h x mg protein) for the sodium-independent process and a Km of 4.8 mM and Vmax of 54.5 nmol/(h x mg protein) for the sodium-dependent process. While sodium dependent uptake was abolished following treatment with metabolic inhibitors, sodium-independent uptake was only slightly impaired. Sodium-independent uptake was inhibited in the presence of the non-metabolizable amino acids, aminoisobutyric acid (AIB) and aminobicyclo(2,2,1)heptane-2-carboxylic acid (BCH), but not by N-methylated amino acid substrates. Sodium-dependent uptake was insensitive to AIB and was completely abolished by BCH. These results indicate that an uptake process for 3HK is present in the mammalian brain, and suggest that the sodium-dependent component of 3HK transport may be mediated by a system which has not previously been described in CNS tissue. PMID- 1515933 TI - Hippocampal laminar glucose utilization and theta rhythm following unilateral fimbria-fornix lesions in rats. AB - Laminar profiles of glucose utilization were related to the presence or absence of movement-related hippocampal theta rhythm in CA1 and dentate gyrus of rats after aspirative unilateral combined lesions of the fimbria-fornix and cingulum. Three groups were studied: (1) sham-operated rats, (2a) lesioned rats with an ipsilateral loss of theta activity at 4 weeks post-lesion that persisted at 12 weeks post-lesion, and (2b) lesioned rats with a loss of theta activity at 4 weeks post-lesion, but a recovery of theta rhythm at 12 weeks post-lesion. Fimbria-fornix/cingulum lesions served both to abolish ipsilateral theta rhythm and to decrease ipsilateral glucose metabolism in all cell layers of CA1 and the dentate gyrus, when normalized to the contralateral hemisphere. Although glucose metabolism in lesioned animals with a recovery of theta rhythm was not as high as control levels, in several laminae it was significantly higher than that of lesioned animals with persistent loss of theta rhythm. These laminae included the dentate hilus and strata oriens, pyramidale and lacunosum-moleculare of CA1. The increased glucose metabolism associated with the return of theta rhythm suggests a functional reinnervation of these layers of the hippocampus in such animals. PMID- 1515934 TI - Involvement of pertussis toxin sensitive G-proteins in conditioned fear potentiated startle: possible involvement of the amygdala. AB - The present study evaluated the effects of intraventricular or intracerebral administration of pertussis toxin on fear-potentiated startle (a measure of conditioned fear) and shock sensitization (a measure of unconditioned fear). In Experiment 1 all animals were unilaterally implanted with cannulae into the lateral ventricle 1 week prior to 2 days of fear conditioning (ten light-shock pairings on each of 2 days). Five days later, animals were infused with either 1 microgram pertussis toxin or saline and tested for fear-potentiated startle 24 h after infusion and tested for shock sensitization 26 or 50 h after infusion. Pertussis toxin blocked the ability of a light conditioned stimulus to facilitate startle but did not alter the ability of acute footshock to increase startle amplitude in the same animals. In Experiment 2 bilateral infusion of 1 microgram pertussis toxin into the basolateral nuclei of the amygdala, but not the interpositus nuclei of the cerebellum, also blocked fear-potentiated startle when animals were tested 6 h after infusion. These findings suggest a role for pertussis toxin sensitive G-proteins, perhaps within the amygdala, in the expression of conditioned but not unconditioned fear. PMID- 1515935 TI - Immunohistochemical evidence that Met-enkephalin and GABA coexist in some neurones in rat dorsal horn. AB - A pre-embedding immunohistochemical method to detect Met-enkephalin was combined with postembedding immunohistochemistry with GABA and glycine antisera, in order to determine whether or not Met-enkephalin coexisted with either of these inhibitory transmitters in neuronal cell bodies within the superficial dorsal horn of the rat. The distribution of immunostaining with the three antisera was similar to that which has been described previously. Of 74 enkephalin immunoreactive neurones in laminae II and III, 51 were immunoreactive with the GABA antiserum and 23 were not. All of the neurones which were not GABA immunoreactive were located in lamina II. None of the enkephalin-immunoreactive cells showed glycine-like immunoreactivity. These results suggest that enkephalin is present both in GABAergic neurones and in neurones which do not contain GABA within the rat superficial dorsal horn. It is likely that the population of neurones immunoreactive with both enkephalin and GABA antisera includes lamina II islet cells and that the population which were enkephalin-immunoreactive but not GABA-immunoreactive includes stalked cells. In addition, this latter group may correspond to those cells which possess both enkephalin- and substance P-like immunoreactivity and which have been described previously in this area. PMID- 1515936 TI - Bombesin, neuromedin C and neuromedin B given intrathecally facilitate the tail flick reflex in the rat. AB - Evidence from an earlier study suggested that bombesin, neuromedin C and neuromedin B may play a role in spinal nociceptive transmission; iontophoretic administration of these peptides onto dorsal horn neurones in the cat was found to preferentially depress those neurones activated by noxious stimulation. Therefore, to further examine the possible function of these peptides in the spinal cord, the present study compares the effects of intrathecal administration of bombesin, neuromedin C and neuromedin B on reaction time in the tail flick test in the rat. Intrathecal injection of bombesin and neuromedin C to the lower lumbar vertebral level produced a dose-dependent decrease in reaction time which lasted up to 46 min. Similar administration of neuromedin B had a biphasic effect; there was a dose-dependent decrease in reaction time lasting about 6 min followed by a delayed increase in reaction time to above control values at 31-46 min. In addition, administration of these peptides induced behavioral responses such as spontaneous vocalization and vocalization in response to innocuous touch. These results provide physiological evidence for a role of neuromedin C and neuromedin B in sensory transmission at the spinal level. In this model, bombesin was a potent agonist which may selectively activate the neuromedin C receptor. PMID- 1515937 TI - Dorsal root potentials and afferent input to the spinal cord in rats with an experimental peripheral neuropathy. AB - Compound action potentials (CAPs), dorsal root potentials (DRPs) and cord dorsum potentials evoked by stimulating the sciatic nerves have been measured in 4 control rats and in 19 rats with a constriction injury of one sciatic nerve produced by loose ligation of the nerve at mid-thigh level 5 days (n = 8) or 10 days (n = 11) before the acute experiments. The contralateral nerve was exposed but not ligated in a sham procedure. In all cases, the nerve was stimulated proximal to the lesion. At 5 days post-operative (PO) the maximal A-fibre CAPs on the nerve-injured side were not significantly different from those on the sham operated side. At 10 days PO all animals showed a decrease in the CAP on the nerve-injured side. The mean CAP area on the nerve-injured side was 74.0% +/- 4.2 of the sham-operated side, which was significantly different (P less than 0.005). The sciatic nerves and L5 dorsal roots from 4 of the 10 day PO animals were examined histologically and showed no signs of demyelination or degeneration. The amplitude and area of the maximal DRPs were significantly smaller on the nerve injured side than on the sham-operated side in all of the nerve-injured animals (P less than 0.01 at 5 days PO; P less than 0.05 at 10 days PO). The mean area of DRPs from the nerve-injured side was 61.7% +/- 10.1 and 46.8% +/- 7.5 of the DRPs from the sham-operated side in the 5 and 10 day PO animals, respectively. The DRPs evoked by sub-maximal afferent volleys were also measured. In all of the nerve-injured animals the CAP-DRP curve on the nerve-injured side was shifted to the right compared to that of the sham-operated side, such that a given size of CAP evoked a smaller DRP on the nerve-injured side than on the sham-operated side. We conclude that the constriction injury produces a decrease in the DRP generated by a volley in the injured nerve and that this change is independent of the decrease in the CAP seen in the injured nerve. We propose that the constriction injury affects the central mechanism responsible for generating primary afferent depolarization (PAD), and thus the pre-synaptic inhibitory control of the afferent input from the injured nerve is impaired. PMID- 1515938 TI - Differential radioligand binding properties of [3H]5-hydroxytryptamine and [3H]mesulergine in a clonal 5-hydroxytryptamine1C cell line. AB - [3H]5-Hydroxytryptamine ([3H]5-HT) and [3H]mesulergine were used to label 5-HT1C receptors expressed in NIH 3T3 mouse fibroblast cells. Using a rapid filtration assay, saturation analysis of the [3H]5-HT radioligand data indicate that the binding is biphasic. Based on computerized analysis of the data, a 2-site model of radioligand binding is significantly more consistent with the data than a one site model (P less than 0.01). The KD values of [3H]5-HT for the 2 populations are 0.5 +/- 0.1 nM and 31 +/- 15 nM, while the Bmax values are 400 +/- 90 pmol/g protein and 3,000 +/- 600 pmol/g protein, respectively. A biphasic binding pattern is also observed with [3H]5-HT using a centrifugation assay (KD1 = 0.6 +/ 0.06 nM, KD2 = 60 +/- 10 nM; Bmax1 = 740 +/- 90 pmol/g, Bmax2 = 4,000 +/- 700 pmol/g). By contrast, saturation analysis of [3H]mesulergine binding is monophasic (KD = 4.7 +/- 0.7 nM) with a Bmax value (6,800 +/- 1,000 pmol/g protein) that is significantly greater than that obtained using [3H]5-HT (P less than 0.01). Drug competition studies confirm that both [3H]5-HT and [3H]mesulergine label at least 2 subpopulations of expressed 5-HT1C receptors in NIH 3T3 cells. 10(-4) M GTP eliminates the high affinity [3H]5-HT-labeled binding sites with minimal effect on the low affinity [3H]5-HT-labeled sites and no effect on [3H]mesulergine-labeled sites. These data demonstrate that at least 2 distinct subpopulations of 5-HT1C receptors in NIH 3T3 cells can be differentiated using radioligand binding techniques. PMID- 1515939 TI - Synaptic inputs to medullary respiratory neurons from superior laryngeal afferents in the cat. AB - Synaptic inputs from afferents in the superior laryngeal nerve (SLN) to medullary respiratory neurons (n = 154) in the dorsal respiratory group (DRG), ventral respiratory group (VRG) and the region of the Botzinger complex (BOT) were studied in anesthetized cats. Single pulse stimulation of the SLN-evoked monosynaptic EPSPs in most inspiratory bulbospinal (I-BS) neurons in the DRG, and disynaptic or oligosynaptic chloride-dependent IPSPs in other I-BS neurons in the DRG and VRG. Stimulation of laryngeal afferents also inhibited oligosynaptically expiratory bulbospinal neurons in the VRG, and all types of respiratory neurons recorded in the BOT region. Oligosynaptic potentials (usually EPSPs) were recorded in inspiratory and expiratory laryngeal motoneurons. These results provide evidence of a processing of SLN-evoked synaptic responses by all tested groups of medullary respiratory neurons. The pathways mediating these synaptic responses are discussed. PMID- 1515940 TI - Differential distribution of cellular forms of beta-amyloid precursor protein in murine glial cell cultures. AB - The production and localization of cell-associated forms of beta-amyloid precursor protein (APP) of Alzheimer's disease was investigated in primary cultures of mouse glial cells. In both oligodendrocytes and astrocytes, immunofluorescence staining with an antibody against the carboxy terminus of APP revealed an intense cytoplasmic immunoreactivity. Immunoblotting of the cell extracts detected differences in the composition of APP between oligodendrocytes and astrocytes, notably the abundance of 107 kDa subtype in oligodendrocytes. Differences in immunoblot patterns were also noted between two buffer-insoluble, membrane-rich subcellular fractions of the glial cells, nuclear-mitochondrial and microsomal; the 119 kDa APP was enriched in the former, whereas the 73 and 115 kDa APPs in the latter. The results suggest that each APP subspecies may play a distinct functional role in different cell types and subcellular fractions. PMID- 1515941 TI - Entrainment of the rat circadian clock controlling the pineal N-acetyltransferase rhythm depends on photoperiod. AB - Entrainment of the circadian clock as a function of time when a light stimulus is presented has been studied in detail while little attention has been paid to a role photoperiod may play in the resetting. To find out whether and how photoperiod affects the entrainment, resetting of the rat circadian pacemaker by delays in the evening light offset and by advances in the morning light onset, respectively, was studied in rats maintained either under a short photoperiod, with 8 h of light and 16 h of darkness per day (LD 8:16) or under a long, LD 18:6 photoperiod. To assess phase shifts of the clock, the suprachiasmatic nucleus controlled rhythm in the pineal N-acetyltransferase (NAT), namely the time of the evening NAT rise and the time of the morning decline, were followed. One day after a delay in lights off, on LD 8:16 the NAT rhythm with a normal amplitude was retained following longer delays of the light offset and the maximum phase delay of the NAT rise was 3 times larger than on LD 18:6. One day after an advance in lights on, the NAT decline was phase advanced under both photoperiods; on LD 8:16 the maximum shift was 3 times as large as on LD 18:6. On LD 8:16, the NAT rise was not shifted after shorter advances in lights on and became phase delayed only when the light onset was brought forward to before midnight while on LD 18:6 the NAT rise was phase delayed after any, even a mere 1 h, advance in lights on. The data show that magnitude and direction of phase shifts of the NAT rhythm depend not only on the time of light presentation but on photoperiod as well. Difference in resetting of the rhythm under various photoperiods may reflect photoperiod-dependent changes of an underlying pacemaker. PMID- 1515942 TI - Ethanol dependence and withdrawal selectively alter localized cerebral glucose utilization. AB - The 2-deoxyglucose technique was used to determine local cerebral glucose utilization (LCGU) in over 50 brain regions of rats physically dependent upon ethanol and compared to those of acutely intoxicated and those undergoing an overt ethanol-withdrawal syndrome. Dependent-intoxicated rats (average blood ethanol concentration 64 mM) had decreased LCGU in 13/54 regions, including those associated with the limbic system, cerebellum, and motor system. The ethanol withdrawal syndrome was associated with 17/50 gray regions showing an increase, including regions involved with motor function, auditory system, and mammillary bodies-anterior thalamus-cingulate cortex pathway. The most pronounced differences between these groups occurred in regions associated with motor function, cerebellar function, anterior thalamus, and median raphe. Comparisons between dependent-intoxicated and acutely intoxicated rats (average blood ethanol concentration 66 mM) revealed that acute intoxication was associated with a relatively greater reduction in LCGU in regions involved with sensory-related functions, mammillary bodies, and median raphe. With the development of dependence, adaptation occurred in these regions except for inferior colliculus and median raphe. Dependence was also associated with a relative decrease in LCGU in white matter, limbic system, and extrapyramidal motor system. PMID- 1515943 TI - An in vitro circadian rhythm of protein synthesis in the rat suprachiasmatic nucleus under tissue culture conditions. AB - Because inhibitors of protein synthesis produce changes in the circadian rhythm of wheel-running activity in rodents, we examined the circadian changes of in vitro protein synthesis by the rat suprachiasmatic nucleus (SCN). We demonstrated a robust circadian rhythm of [14C]leucine incorporation as well as [3H]2 deoxyglucose (2DG) uptake by the SCN. The peak time of 2DG uptake was around circadian time 6-9 h (CT6-CT9). In contrast to 2DG uptake, the maximum rate of leucine incorporation occurred around CT22-CT0. Thus, the leucine incorporation rate preceded 2DG uptake by 6-9 h. Leucine incorporation was inhibited by protein synthesis inhibitors, but not by tetrodotoxin. Since a robust circadian rhythm of leucine incorporation by the SCN was detected in vitro by using our method, this procedure may be useful to study the circadian clock function of the SCN. PMID- 1515944 TI - Microinjection of opioid antagonists into the substantia nigra reduces stress induced eating in rats. AB - Stress produced by pinching the tail has been shown to cause satiated animals to eat and to display oral stereotypies. Endogenous opioids and central dopamine systems have been implicated in the mediation of these effects. In order to test the possibility that the substantia nigra (SN) might be involved, the amount of food intake and gnawing produced by mild tail pinch were assessed following bilateral microinjections of opioid antagonists into the SN. Evaluations of nociceptive thresholds were also conducted using tail flick and hot plate tests. Eating induced by tail pinch was reduced by microinjections of the non-selective opioid antagonist naloxone (3, 10, 20 and 30 nmol) and by the mu-selective antagonist Cys2, Tyr3, Orn5, Pen7 Amide (CTOP) (1, 3 and 10 nmol). These effects on eating occurred in the absence of effects on gnawing. kappa- and delta antagonists (10 nmol) had no effect on eating or gnawing. Naloxone did not alter either tail flick or hot-plate response latencies. The highest dose of CTOP increased response latency on the hot-plate test only. The results are interpreted as suggesting that the SN may be an important central site of action for opioid antagonists in reducing stress-induced eating. The possibility that the SN may be a central site mediating the effects of dopamine on this phenomenon is also discussed. PMID- 1515945 TI - Microheterogeneity of dopamine transporters in rat striatum and nucleus accumbens. AB - Previously we have shown that the [125I]DEEP-labeled dopamine transporter from the rat nucleus accumbens has a higher apparent molecular weight than that from striatum. The present study confirms and extends these observations. Experiments with nucleus accumbens showed [125I]-DEEP to specifically bind to a protein with an apparent molecular weight of 76 kDa and with the pharmacological properties of the dopamine transporter. In exoglycosidase studies, treatment with neuraminidase, but not alpha-mannosidase, reduced the apparent molecular weight of the dopamine transporter from both the striatum and nucleus accumbens; however, a difference in the apparent molecular weight was still observed. N Glycanase treatment, on the other hand, did reduce the apparent molecular weight of the dopamine transporters from the two regions to a similar value, approximately 56 kDa. In radioligand binding studies examining the effect of partial deglycosylation on striatal dopamine transporters, neuraminidase did not affect specific [3H]WIN 35,428 binding at 4 and 40 nM concentrations. In conclusion, the present study demonstrates that the difference in the apparent molecular weight of the dopamine transporter from these two regions is due to a difference in glycosylation and that the dopamine transporter from both regions contains similar amounts of sialic acid in their carbohydrate structure. Furthermore, the present data also indicate that the polypeptide portion of the dopamine transporter from both regions could be the same gene product. PMID- 1515946 TI - Serotonergic projections from the midbrain periaqueductal gray and nucleus raphe dorsalis to the nucleus parafascicularis of the thalamus. AB - By a double-labeling method combining the retrograde tracing of horseradish peroxidase and the immunocytochemical technique, serotonin-like immunoreactive neurons in the midbrain periaqueductal gray (PAG) and nucleus raphe dorsalis (DR) of the rat were observed to send projection fibers to the nucleus parafascicularis of the thalamus bilaterally with an ipsilateral dominance. These serotonin-containing projecting neurons were observed mainly at the middle-caudal levels of the ventrolateral subdivision of the PAG and less at the middle-rostral levels of the DR. PMID- 1515947 TI - Repeated corticosterone administration sensitizes the locomotor response to amphetamine. AB - Repeated exposures to stressful situations has been shown to increase individual reactivity to psychostimulants, although the biological factors involved in such stress-induced changes are still poorly understood. In this study, we investigated the role of corticosterone in the effects of stress on the response to psychostimulants. We found that repeated corticosterone administration (both 1.5 mg/kg, intraperitoneally and 50 micrograms/ml in drinking water, once per day for 15 days) increased the locomotor response to amphetamine (1.15 mg/kg, i.p.). At the doses used in these experiments, corticosterone administration induced similar increases in plasma levels of the hormone to those induced by stress. These results suggest that corticosterone secretion may be one of the mechanisms by which repeated stress increases the behavioral responses to amphetamine. Since an enhanced reactivity to psychostimulants has been found to be an index of a propensity for drug self-administration and a model of certain psychopathological conditions, these findings point to a role for glucocorticoids in such abnormal states. PMID- 1515948 TI - Na(+)-activated K+ channels are widely distributed in rat CNS and in Xenopus oocytes. AB - We recorded the activity of K+ channels activated by sodium (KNa channels) in two widely used preparations, primary cell cultures prepared from neocortex, cerebellum, midbrain, brainstem and spinal cord, and Xenopus oocytes. KNa channels from all regions shared an absolute dependence on [Na+], had conductances of 140-170 pS in symmetrical 150 mM K+ and exhibited characteristic substates. The role of this channel must now be considered in terms of its widespread distribution. PMID- 1515949 TI - Citalopram's ability to increase the extracellular concentrations of serotonin in the dorsal raphe prevents the drug's effect in the frontal cortex. AB - Administered intraperitoneally to rats at 1 mg/kg, citalopram, a potent and selective inhibitor of serotonin uptake, significantly increased dialysate serotonin in the dorsal raphe, but not in the frontal cortex. At 10 mg/kg citalopram had a greater effect on raphe serotonin and a moderate and short lasting increase in the dialysate serotonin in the frontal cortex. Citalopram 1 mg/kg i.p. significantly increased the extracellular concentration of serotonin in the frontal cortex of rats which had received a continuous infusion of 1 microM methiothepine in the dorsal raphe, a condition which by itself did not change cortical serotonin concentrations. The results suggest that the ability of serotonin uptake inhibitors to enhance the extracellular concentrations of serotonin in the dorsal raphe attenuates the drug's effect in the frontal cortex. PMID- 1515950 TI - Spinal and trigeminal lamina I input to the locus coeruleus anterogradely labeled with Phaseolus vulgaris leucoagglutinin (PHA-L) in the cat and the monkey. AB - Terminal fibers anterogradely labeled with Phaseolus vulgaris leucoagglutinin (PHA-L) were observed in the locus coeruleus in the brainstem of the cat and the cynomolgus monkey following injections in lamina I of the spinal or medullary dorsal horn. Thus, thermoreceptive- or nociceptive-specific lamina I cells that project to the locus coeruleus could directly influence arousal, vigilance, and the descending control of spinal integration. PMID- 1515951 TI - Excitatory amino acid antagonist administered via microdialysis attenuates lactate accumulation during cerebral ischemia and subsequent hippocampal damage. AB - Our previous studies have shown that kynurenic acid (KYN), a broad-spectrum antagonist of excitatory amino acids (EAAs), administered in situ through a dialysis probe can delay the massive ionic fluxes in the rat hippocampus during cerebral ischemia. The present experiments demonstrated that the same procedure attenuates the increase in extracellular concentration of lactate ([lactate]e) during ischemia as measured by microdialysis. This finding suggests that the lactate accumulation is partially caused by a sudden increase in energy demand due to the rapid ionic fluxes through EAA-coupled ion channels. This inference is consistent with the hypothesis that the earlier ionic event during ischemia is a cause of energy depletion, rather than the result merely of energy failure. The present experiments also revealed that KYN administered by the same procedure attenuates death of hippocampal CA1 pyramidal cells after 5-min transient ischemia in gerbils. Since lactate accumulation is likely to be an important factor affecting cell viability, the protective effect of KYN may be attributable, in part, to inhibition of lactate accumulation. PMID- 1515952 TI - Effect of amygdala kindling on the in vivo release of GABA and 5-HT in the dorsal raphe nucleus in freely moving rats. AB - Our laboratory has previously reported a significant subsensitivity to iontophoretically applied GABA (gamma-aminobutyric acid) in dorsal raphe neurons of amygdala-kindled rats. This subsensitivity was selective for GABA and persisted at least 3 months after the last kindled seizure. In the present series of experiments, we explored mechanisms by which kindling could result in persistent GABA sensitivity changes, using in vivo microdialysis to quantitate neurotransmitter [including GABA and 5-hydroxytryptamine (5-HT)] release in the dorsal raphe nucleus of awake, unrestrained amygdala-kindled rats. Depolarization induced release of GABA is markedly increased in the dorsal raphe nucleus in amygdala-kindled animals. This change in depolarization-induced GABA release appeared to be graded, dependent upon the stage to which the animal is kindled. Thus GABA release is increased in animals kindled to Stage 2 and even greater in animals kindled to Stage 5 seizures. The change in GABA release is also selective, since no consistent change in the release of other putative amino acid neurotransmitters or 5-HT was observed in these same animals. We hypothesize that this increase in depolarization-induced release of GABA in the amygdala-kindled animal underlies the development of subsensitivity to GABA in dorsal raphe neurons. PMID- 1515953 TI - Effect of delayed treatment with nerve growth factor on choline acetyltransferase activity in the cortex of rats with lesions of the nucleus basalis magnocellularis: dose requirements. AB - Rats received bilateral ibotenic acid-lesions of the nucleus basalis magnocellularis. Starting two weeks after the lesion, cytochrome c (0.3 micrograms/rat/day) or 0.01, 0.1, 1 or 10 micrograms/rat/day human recombinant nerve growth factor (NGF) was infused into the lateral ventricle. The highest dose of NGF reduced the weight gain of the animals. Six weeks, but not two weeks of treatment with 10 micrograms/rat/day NGF increased choline acetyltransferase (ChAT) activity in the frontal cortex, parietal cortex and hippocampus, predominantly on the side of the ventricular cannula. The 1 microgram/rat/day dose only increased ChAT activity in the frontal cortex on the infused side. Six weeks of treatment with 10 micrograms/rat/day NGF increased the size, but not the number of NGF-receptor-immunoreactive neurons in the nucleus basalis. This treatment did not affect the levels of dopamine, norepinephrine and serotonin in any of the brain regions studied. These data suggest that prolonged treatment with relatively high doses of NGF is necessary to increase ChAT activity in cortical regions of nucleus basalis-lesioned rats. This treatment will also increase ChAT activity in the intact septohippocampal system, but does not affect the levels of several non-cholinergic neurotransmitters. PMID- 1515954 TI - Analgesic effects of intraventricular and intrathecal injection of morphine and ketocyclazocine in the infant rat. AB - Little is known of the neural bases of analgesia in immature animals. This experiment examined the effects of intracerebroventricular (i.c.v.) and intrathecal (i.t.) administration of morphine or ketocyclazocine in tests of antinociception in rats aged 3 to 14 days of age. Analgesia tests were conducted using both thermal and mechanical (pressure) noxious stimuli applied to the forepaw, hindpaw or tail. In the 3-day-old morphine-injected i.c.v. produced analgesia in the forepaws when either the mechanical or thermal noxious stimulus was used. There was no effect when the hindpaw or tail was tested. At 10 days of age, when the mechanical stimulus was used, morphine was analgesic in tests on all three appendages but was only effective in the forepaw when the thermal stimulus was used. Morphine was fully effective in all tests with both stimuli at 14 days of age. Ketocyclazocine had no consistent effect when given i.c.v. When injected i.t., morphine produced analgesia in the forepaws in the thermal test at 4 days of age and in all appendages by 10 days. When the mechanical test was used, morphine was effective in all appendages at all ages tested. Ketocyclazocine was analgesic at all appendages for the mechanical stimulus at all ages but was only transiently effective in the thermal test. The results demonstrate differential development of analgesia mediated at different levels of the neural axis and are consistent with the development of descending inhibitory that may mediate analgesia induced by i.c.v. injections of morphine. Neural mechanisms that are involved in the analgesic effects of these drugs against the two types of stimuli are also developmentally distinct. PMID- 1515955 TI - [High frequency jet ventilation in heated gas saturated in water vapor without a reserve of medical gas under pressure. An original method]. AB - A prototype of high frequency jet ventilator is compared with a classic device: Gambro Soxijet ventilator. The advantages of the prototype are: no need of pressured medical gas; warming and saturated moisture of the gas. A powerful compressor (2 M3.H-1 flow--3 bar pressure) draws up the moistened and warmed gases and injects them into a double pneumatic capacity. The first capacity is pressure limited by a relief valve (3 bar). Exhausted gases flow back to the pump. A miniature pressure regulator, placed between the two capacities, rules the driving pressure. Gas mixture is injected through a solenoid valve controlled by an electronic twin-timer. Results of both devices are similar. However, our prototype seems to be very convenient for developing countries where medical gases under high pressure are not often available. PMID- 1515956 TI - [Premedication with midazolam in infants. A comparison of different modes of administration]. AB - Midazolam presents the properties of a good premedication because of its sedative and anxiolytic activity. The aim of this study, concerning 84 children, was to compare the efficacy of midazolam according to the three ways of administration: intrarectal, oral and intranasal, in reference to a group without premedication. Results have shown the superiority of intrarectal midazolam at the dose of 0.35 mg.kg-1 30 minutes before surgery. The tolerance of this way of administration is excellent and it allows a greater sedative activity compared to the control group and to the intranasal group. PMID- 1515957 TI - [Nicardipine vs trinitrin for controlled hypotension in maxillo-facial surgery]. AB - In this study we examined perioperative blood losses during maxillo-facial surgery comparing 2 techniques for controlled hypotension using nitroglycerin (NTG) and nicardipine (NICAR). 37 ASA I and II patients electively scheduled for rhinoseptoplasties under general anaesthesia were randomly divided into 2 groups. General anaesthesia was induced with intravenous thiopental and vecuronium following a neuroleptanalgesia consisting of fentanyl (0.053 +/- 0.004 microgram.kg-1.min-1) IV and droperidol (1.98 +/- 0.35 microgram.kg-1.min-1) IV given in bolus doses. The patients were intubated and ventilated (N2O in O2) to maintain normocarbia. Controlled hypotension to maintain a mean arterial pressure (MAP) between 50 and 55 mmHg was induced using an IV infusion of NTG 6 micrograms.kg-1.min-1 in group I and NICAR 10 micrograms.kg-1.min-1 over 10 minutes followed by an infusion at 4 mg.kg-1.min-1 for group II. Measurements of heart rate (HR), systolic blood pressure (SBP), diastolic blood pressure (DBP), MAP using an automated blood-pressure cuff and end tidal carbon dioxide (ETCO2) were recorded prior to induction (PREIND), intraoperatively (PEROP) at 15, 30, 40 and 120 minutes post-induction, and at 15, 30 and 60 minutes postoperatively (POSTOP). Blood loss, graded as minimal or frank, was assessed by the surgeon during the operative period, post-extubation and 3 days postoperatively at dressing removal. The surgeon was unaware of the randomization schedule. Student's test was applied for statistical analysis of measured variables and Fisher's test for qualitative parameters. No statistically significant differences were noted between both groups with respect to demographic data, duration of surgery and total doses of anaesthetic agents (Table I).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1515958 TI - [Ten years' locoregional anesthesia in children in a private hospital]. AB - Retrospective study during a ten years period of 5,512 regional anaesthesias on children in a private hospital. This work identifies the peculiarities due to recruiting and to RA techniques, shows the practical conditions (preoperative samples, equipment, drugs) and studies the complications, before pointing out good practice rules. PMID- 1515959 TI - [Truncal blocks of the lower limb]. AB - Plexus nerve blocks of the lower limb have been described for many years but were seldom used until recently. Postoperative analgesia is one of the main indications of these blocks. The blockade of both lumbar and sciatic plexuses is required for most of the surgical procedures performed on the proximal part of the lower limb. Nerve stimulators account for less difficulties to perform such blocks and results are more reliable. Several pharmacokinetic studies have documented that toxic thresholds of plasma concentrations of local anaesthetics are not reached with the doses commonly injected. Many different techniques and landmarks have been described providing several alternatives to perform these blocks according to the type and the localisation of the surgical procedure. Extensive indications are reported for day case surgery or patients at risk. PMID- 1515960 TI - [Delirium tremens. Recent neurophysiologic concepts and therapeutic outlook]. AB - Delirium tremens is linked with a chronic depression of the central nervous system by alcohol and a compensatory hyperactivity of neurotransmitters. A sudden stoppage of alcohol intake induces excessive production of these transmitters. Firstly appearing is a noradrenergic hyperactivity which may be responsible not only for reducing the magnesium blood level but also for activating the other transmitter systems. A magnesium blood level lower than 1 mmol.l-1 involves a risk of seizures and requires IV magnesium sulfate. Noradrenergic hyperactivity can be prevented by IV alcohol associated with sedation best achieved by IV clomethiazole in alcoholic solution. Should these preventive measures fail, noradrenaline action in the central nervous system can be blocked by clonidine. Should hallucinations become manifest, linked to dopaminergic hyperactivity, haloperidol is indicated. Benzodiazepines may be useful, particularly carbamazepine, for their depressing effect on gaba-ergic hyperactivity. PMID- 1515961 TI - [The HELLP syndrome and associated toxemia]. PMID- 1515962 TI - [A postoperative syndrome of confusion and stupor or a central anticholinergic syndrome?]. AB - A case is reported of a 23 year old man who sustained a central anticholinergic syndrome after undergoing upper limb surgery under regional anaesthesia and sedation with 2 mg midazolam and 75 micrograms fentanyl. The disturbances consisted of excitation and inhibition. On the 4th postoperative day, he developed progressive coma, quickly and totally reversed with 2 mg physostigmine. Chronic benzodiazepine therapy seems to be a facilitating factor of central anticholinergic syndrome. The low rate of this postoperative complication seems to proceed from failure to recognize it. Differential diagnosis and place of physostigmine therapy are discussed. PMID- 1515963 TI - [The practice of complementary preoperative examinations: its evolution in a general hospital center]. PMID- 1515964 TI - [Retrobulbar anesthesia for cataract surgery. Apropos of 200 cases]. PMID- 1515965 TI - Late adverse effects of treatment among patients cured of cancer during childhood. PMID- 1515966 TI - Long-term survivors of childhood cancer: evaluation and identification of sequelae of treatment. PMID- 1515967 TI - Neuropsychological and psychosocial effects of childhood leukemia and its treatment. PMID- 1515968 TI - Revision in American Cancer Society recommendations for the early detection of colorectal cancer. PMID- 1515969 TI - Ewing's sarcoma. PMID- 1515970 TI - Vertebrobasilar insufficiency related to cervical spondylosis. A case report and review of the literature. AB - A 64-year-old man suffered from symptoms of vertebrobasilar insufficiency (VBI) while turning his head to the left. Roentgenograms of the cervical spines showed severe spondylosis. Cerebral angiography demonstrated compression of the left vertebral artery by osteophytes of the cervical spine when the patient turned his head to the left. He was treated surgically by fixation of the vertebral bodies with good relief of symptoms during one year of follow-up. VBI induced by spondylotic compression of the vertebral artery is uncommon. We therefore reviewed the literature and suggested a more simple method of operation. PMID- 1515971 TI - Idiopathic palatal myoclonus: report of two cases. AB - We report two patients with idiopathic palatal myoclonus presenting as a synchronous up-and-down beating of the soft palate, to-and-fro thrusting of the tongue, and contraction of pharyngeal and laryngeal muscles. The obvious pulsatile movements were visible on the submental surface and a loud clicking noise was audible from a distance. The involuntary jerkings predominantly appeared when the mouth was kept shut, but could be interrupted by some oro lingual maneuvers such as phonation, swallowing, and sticking the tongue out. Although the palatal myoclonus did not affect the function of the mouth, the patients were socially embarrassed by the loud clicking sound and pulsatile movements. On clinical examination and laboratory investigations, no evidence of lesion in the brainstem or cerebellum was obtained. A therapeutic trial with trihexyphenidyl did not bring any benefit. To conclude, because the idiopathic palatal myoclonus is a rare movement disorder which has never been documented in Taiwan, we describe its clinical characters in two Chinese patients and discuss the differential diagnosis with other involuntary lingual movements. PMID- 1515972 TI - Gastric adenocarcinoma simulating benign gastric ulcer. AB - The pathologic features and prognosis of patient in whom gastric cancer simulates at endoscopy as a benign gastric ulcer has been poorly characterized. We performed a retrospective study with particular reference to the long term prognosis on 191 patients treated for gastric adenocarcinoma over the period 1980 1986. In 176 of these 191 patients (92.2%), the endoscopic findings suggested cancers, while in the remaining 15 patients (7.8%), the endoscopic appearance suggested benign ulcer. Comparing gastric cancers masquerading as benign gastric ulcers with those appeared malignant endoscopically, the former had higher resectability rate (100% vs 77.3%), higher incidence of early gastric cancer (73.3% vs 6.25%), less poorly differentiated carcinoma (33.3% vs 65.4%), less lymph node metastasis (13% vs 69.5%) and a higher five-year survival rate (86.6% vs 24.8%) (p less than 0.05 in all). Our study indicated that gastric adenocarcinomas simulated benign gastric ulcers at endoscopy are mostly early gastric cancers that carry a much better prognosis. PMID- 1515973 TI - Effect of heart rate on pressure half-time in patients with mitral stenosis. AB - The effect of heart rate on pressure-half time has been controversial. This study attempted to clarify this issue in patients with mitral stenosis. Twenty cases were enrolled, 10 with atrial fibrillation and 10 with sinus rhythm. Twenty beats were analyzed for each patient. The results showed that in patients with atrial fibrillation the pressure half-time was hardly measurable in the cardiac cycles with a ventricular rate more than 100/min; by excluding these fast beats, the pressure half-time showed no relationship with the heart rate. Similarly, there was no significant correlation between heart rate and pressure half-time in patients with sinus rhythm when the heart rate was less than 70/min. However, if the sinus rate was more than 70/min, the correlation became statistically significant. We conclude that when using pressure half-time to derive mitral valve area we should avoid to use the beats with ventricular rate greater than 100/min in patients with atrial fibrillation. In patients with sinus rhythm, we should try to use those beats with heart rate greater than 70/min if possible. Otherwise, significant error may occur. PMID- 1515974 TI - A prospective randomized controlled trial of sandostatin and vasopressin in the management of acute bleeding esophageal varices. AB - To study the hemostatic effect of Sandostatin, a long-acting analogue of somatostatin, in acute variceal bleeding, a prospective randomized controlled trial comparing it with Vasopressin was conducted in 41 cirrhotic patients with esophageal variceal bleeding. Initial hemostasis was achieved within 6 hours in 75% of patients treated with Sandostatin and in 61.9% treated with Vasopressin. Recurrent bleed developed in 20% of patients in Sandostatin group and 46.2% in Vasopressin group following initial hemostasis. Complete control of bleeding for 24 hours was attained in 60% of the Sandostatin group and in 33.3% of the Vasopressin group. There was no statistically significant difference in both the rate of initial hemostasis and complete bleeding control. Hospital mortality was also similar in both groups. However, transfusion requirements were less (P less than 0.05) and side effects tended to be milder in patients treated with Sandostatin. In conclusion, Sandostatin is at least as effective as Vasopressin in the treatment of acute variceal bleeding, and carries less severe complications than Vasopressin does. PMID- 1515976 TI - [Measurements of dose distribution in small fields of 10 MV X-rays]. AB - Dose distribution measurement in small fields include: 1. Field size factor, 2. Percentage depth dose, 3. Isodose curves charts, 4. Tissue-phantom ratio, and 5. Penumbra width. Field size factor was measured by using different detectors and it was found that the dimension of detector must be less than half of the field size to avoid under-estimation. If a 0.6 cc cylindrical ion chamber was used for small fields measurement, it would under-estimate the field size factor by 19.7% for a 2x2 cm2 field. The percentage depth dose and the tissue-phantom ratio increased with increasing the field size. The penumbra width increased with increasing the field size which was larger for a square field than the corresponding circular field by less than 1 mm. PMID- 1515975 TI - [Valve replacement for aortic stenosis]. AB - We retrospectively reviewed 122 consecutive patients with aortic stenosis from January 1977 to December 1990. There were 68 male and 54 female patients. Their age ranged from 5 to 73 years old (47 +/- 16, mean +/- SD). Sixty eight patients also had associated mitral valve lesion, 13 patients had tricuspid valve lesion, and 3 patients had coronary artery disease. Aortic valve replacement was performed on all patients. Mechanical valves were implanted in 86 cases and tissue valves in 36 cases. Associated procedures were performed in 54 cases: mitral valve replacement in 34 cases, mitral valve repair in 18 cases and coronary artery bypass grafting in 2 cases. A bicuspid aortic valve was found in 20 cases (16.4%). Hospital mortality was 4.9% (6 cases). Follow-up was completed in 95% of the surviving cases (110 cases). The survival rate was 82 +/- 3% at 13 years and redo-free rate was 73 +/- 8% at 13 years. Seven cases required redo operation, due to tissue valve degeneration in 5 and thrombosis of the mechanical valve in 2. All 7 patients survived. Late death occurred in 6 cases: 3 from malignancy, 2 from stroke and 1 from ventricular arrhythmia. We concluded that valve replacement for aortic stenosis is a safe and satisfactory procedure with good long-term results. PMID- 1515977 TI - Abdominal embryonal rhabdomyosarcoma. A case report. AB - Rhabdomyosarcoma is the most common soft tissue sarcoma in childhood, but it is rare in young adults. It usually occurs in the pelvis or genito-urinary tract. We report a case of abdominal embryonal rhabdomyosarcoma who received a combined treatment modality with radical pelvic surgery and combination chemotherapy of vincristine, actinomycin-D and cyclophosphamide (VAC). She is well with no evidence of tumour recurrence for 3 years after primary surgery. PMID- 1515978 TI - Role of areca nut consumption in the cause of oral cancers. A cytogenetic assessment. AB - BACKGROUND: Cytogenetic studies, framed to assess the possible genomic damage caused by areca nut consumption (without tobacco and not as a component of betel quid), were performed among areca nut chewers, which included normal people who chew areca nuts, patients with oral submucous fibrosis, and patients with oral cancer, and healthy nonchewing controls. RESULTS: The analysis showed statistically significant increases in the frequencies of sister chromatid exchanges and chromosome aberrations in peripheral blood lymphocytes and the percentage of micronucleated cells in exfoliated cells of buccal mucosa among all three groups of chewers when compared with those of the controls. CONCLUSIONS: The current data, the first of this type among only areca nut chewers, highlight that this popular masticatory is erroneously considered "safe" and that it increases the genomic damage even when chewed without tobacco. The data also signify that, henceforth, in cytogenetic biomonitoring, areca nut consumption also should be considered as one of the confounding factors. PMID- 1515979 TI - Familial nasopharyngeal carcinoma in patients who are not Chinese. AB - BACKGROUND: Nasopharyngeal carcinoma (NPC) is a malignancy that is prominent in Cantonese Chinese people. It is presumed to result from an interaction of genetic and environmental factors, including the Epstein-Barr virus (EBV). In an attempt to further clarify the pathogenesis of this disease, an evaluation of NPC occurring in racial/ethnic groups not considered susceptible to this disease could be informative. METHODS: A white family with NPC occurring in three siblings was investigated and information was gleaned from literature on other reports of familial NPC in non-Chinese families. RESULTS: In the family being investigated, another genetically determined disease, hemophilia, was identified. Radiation early in life was noted to be a possible risk factor for NPC in the proband. A review of familial NPC in the white population revealed that in contrast to sporadic NPC, which is usually of the well-differentiated type, familial NPC usually is poorly differentiated. CONCLUSIONS: Familial NPC offers an important opportunity to investigate the etiology of this disease. With newer laboratory techniques to investigate pathogenetic mechanisms, detailed evaluations of non-Chinese NPC families may become increasingly important. PMID- 1515980 TI - Pathology and prognosis of gastric carcinoma. Findings in 10,000 patients who underwent primary gastrectomy. AB - BACKGROUND: Despite recent advances in diagnosis and treatment, gastric carcinoma remains a major cause of death in the world. METHODS: The clinicopathologic profile of 10,000 consecutive patients who underwent primary gastrectomy during 1962-1989 were reviewed and prognostic factors influencing survival in those with gastric carcinoma were analyzed in 7031 patients. RESULTS: Incidence of gastrectomy for carcinoma has increased steadily and the rate of early carcinoma exceeded that of advanced carcinoma in the recent period of 1985-1989. Five-year and 10-year survival rates were 46.1% and 35.2% in 3868 patients with advanced carcinoma, and 88.8% and 77.3% in 3163 patients with early carcinoma, respectively. In patients with advanced carcinoma, significantly poorer survival rates were noticed for patients older than 70 years of age, those who underwent total gastrectomy, tumors involving the entire stomach or greater than 10 cm in diameter, a macroscopic diffusely infiltrative pattern, adenosquamous histologic type, positive surgical resection margins, or lymph node metastasis. None of the above poor prognostic features were identified in patients with early gastric carcinoma group except for those older than 70 years of age. Although lymph node metastases were present in 10% of early gastric carcinomas, this feature did not impart a poor prognosis. Patients with advanced carcinoma grossly resembling an early carcinoma had an intermediate prognosis, suggesting the existence of a developmentally midstage lesion between early and advanced carcinoma. CONCLUSIONS: The study illustrates that the most important role for clinicians treating with gastric carcinoma should be early detection and aggressive surgery for resectable tumors, followed by detailed pathologic examination. PMID- 1515981 TI - Serum cholesterol level, body mass index, and the risk of colon cancer. The Framingham Study. AB - BACKGROUND: Some studies have linked low serum cholesterol levels to increased risk of colon cancer, particularly in men. Results have been inconsistent, with preclinical disease frequently offered to explain any apparent association. METHODS: The Framingham Study cohort of 5209 persons, initially 30-62 years of age and observed more than 30 years, was evaluated. Baseline data included lipoprotein fractions, total cholesterol levels, body mass index, alcohol intake, and cardiovascular risk variables such as cigarette smoking, hypertension, and glucose intolerance. RESULTS: In this population, colon cancer in men is related inversely to serum cholesterol levels, even when the first 10 years of follow-up are eliminated to reduce the effect of preclinical disease. This effect is concentrated in the Svedberg 0-20 fraction, corresponding to low-density lipoprotein levels. Another finding only in men is the direct relation of body mass index to colon cancer incidence. CONCLUSIONS: Combined initial low serum cholesterol levels and obesity appear to indicate a four times greater risk for colon cancer in men as compared with people with average values of both variables. The reasons for these observations are unknown. PMID- 1515982 TI - A new enzyme-linked lectin/mucin antibody sandwich assay (CAM 17.1/WGA) assessed in combination with CA 19-9 and peanut lectin binding assay for the diagnosis of pancreatic cancer. AB - BACKGROUND: Mucus glycoproteins are often present in the sera of patients with pancreatic cancer, and their detection and quantification can be used in serologic diagnosis. METHODS: A novel enzyme-linked "sandwich" assay (CAM 17.1/WGA) has been developed in which a lectin, wheat germ agglutinin (WGA), is bound to the solid phase to capture serum glycoproteins, and after addition of test sera, a monoclonal antimucin antibody (CAM 17.1) and peroxidase-tagged second antibody are used as a detection system. RESULTS: The test has been applied to sera from 79 patients with pancreatic cancer and 120 controls. The CAM 17.1/WGA assay alone had a sensitivity of 78% and specificity of 76% in the diagnosis of pancreatic cancer. Combination of the CAM 17.1/WGA test with a previously described peanut lectin binding assay (PNA/ELLA) provided a sensitivity of 92% and specificity of 70%, whereas combination of the CAM 17.1/WGA assay with the CA 19-9 radioimmunoassay had a sensitivity of 85% and specificity of 76%. Combination of all three tests had a sensitivity of 94% and specificity of 66%. In nonjaundiced patients, the combination of CAM 17.1/WGA and PNA/ELLA had a sensitivity of 93% and specificity of 79% in the diagnosis of pancreatic cancer. CONCLUSIONS: This new test adds significantly to the armamentarium of serologic tests for pancreatic cancer. These tests are particularly effective when used in combination to detect different mucin-borne carbohydrate antigens. They deserve more widespread use, particularly in examining nonjaundiced patients with unexplained abdominal pain or weight loss. PMID- 1515983 TI - Malignant lymphomas of the upper gastrointestinal tract. Results of a prospective study in 103 patients. AB - BACKGROUND: There is a discrepancy between the incidence of gastrointestinal involvement by malignant lymphomas, as established in postmortem studies, and the rareness of the corresponding clinical diagnosis. METHODS: Therefore, the authors performed routine upper gastrointestinal endoscopic examination, within the framework of the usual staging examinations, in 103 consecutive patients with newly diagnosed Hodgkin disease (n = 21) and non-Hodgkin lymphoma (n = 82). RESULTS: One patient with Hodgkin disease (4.8%), 11 of 40 patients (27.5%) with non-Hodgkin lymphoma of low-grade malignancy, and 11 of 42 (26.2%) of those with highly malignant non-Hodgkin lymphoma showed involvement of the gastric and/or duodenal mucosa, as diagnosed with esophagogastroduodenoscopy. Of the 22 patients with non-Hodgkin lymphoma, 9 had involvement of other mucosa-associated lymphoid or epithelial tissue. In two patients with Stage III, two with Stage II, and two patients with presumptive Stage I disease, the disease was reclassified as Stage IV. Because of gastrointestinal involvement, treatment for two patients was changed from radiation therapy to chemotherapy and another two patients had gastric resections so that possible treatment-related complications could be avoided. CONCLUSIONS: In light of these results and the fact that a major basis for the therapeutic strategy for malignant lymphomas is tumor stage, routine esophagogastroduodenoscopic examination within the framework of the usual staging examinations is recommended. In individual cases, this procedure may be of decisive importance in the therapeutic approach to and prevention of complications. PMID- 1515984 TI - Sinonasal fibrosarcomas, malignant schwannomas, and "Triton" tumors. A clinicopathologic study of 67 cases. AB - BACKGROUND: Sinonasal fibrosarcomatous neoplasms are uncommon tumors and there are no previous studies of a large number of such cases. The clinical and histologic features of 67 fibrosarcomatous neoplasms of the nasal cavity and paranasal sinuses are reported. METHODS: Multiple clinical and histologic parameters (including immunostain results) were analyzed to characterize the features important for histologic recognition of the tumors and for correlation with patient outcomes. RESULTS: Some tumors could be classified as malignant schwannomas or malignant "Triton" tumors, but their behavior was similar to that of the fibrosarcomas. Histologically, most tumors were very low-grade malignant neoplasms; however, 22% of patients died of their tumors. Factors that correlated with death were mitotic rate (greater than 4 mitoses per 50 high-power fields), increased tumor cellularity, and male sex. CONCLUSIONS: Many tumors originally were diagnosed as benign (by others), probably causing initial undertreatment of some patients. Proper recognition and histologic evaluation of the tumor are important to ensure the best therapy and optimal patient survival. PMID- 1515985 TI - New aspects in the staging of lung cancer. Prospective validation of the International Union Against Cancer TNM classification. AB - BACKGROUND AND METHODS: To validate the new TNM definitions for lung cancer (International Union Against Cancer [UICC] TNM classification, 4th edition, 1987), the data of 3823 patients were analyzed prospectively in terms of concordance between clinical (TNM) and pathologically confirmed classification (pTNM), the value of the various diagnostic techniques in estimating the pathologically confirmed classification, and the prognostic relevance of the new TNM definitions. RESULTS: With regard to the primary tumor (T), clinical and pathologic classifications were identical in 63%; with regard to lymph node involvement (N), the agreement was 47%; for distant metastasis agreement occurred in 91% of cases and for the stages it occurred in 56%. As to the primary tumor (T), the accuracy of radiography (59%) was nearly identical to that of computed tomography (CT) (58%). Both techniques were less precise in determining the extent of lymph node involvement (CT, correct assessments in 50%; radiography, correct assessments in 43%). The statistically significant differences in the prognosis for the T, N, and M categories and for the stages and the categories of the new R classification could be confirmed. Allowance should be made for the different prognosis between T1N0M0 and T2N0M0 by the new Substages IA and Ib of Stage I. CONCLUSIONS: By the new TNM definitions for bronchus carcinoma, international conformity became feasible and practical, and the improvement of its prognostic relevance provided a more reliable basis for establishing guidelines for individual oncologic concepts. PMID- 1515986 TI - Sensitive and specific detection of the 4B5 antigen in bronchial lavage specimens from patients with primary bronchogenic carcinoma. AB - The monoclonal antibody 4B5 binds to a mucin-like antigen elaborated by respiratory epithelium of patients with non-small cell bronchogenic carcinoma. Several immunoassay formats were used to determine the presence of the antigen in lavage specimens. A qualitative immunodrop binding assay showed immunoreactivity in 37 (64%) of 58 specimens from patients with non-small cell lung cancer. In contrast, only 11 (12%) of 93 specimens from patients with either metastatic carcinoma or benign pulmonary diseases exhibited 4B5 immunoreactivity. A quantitative radioimmunoassay using standardized amounts of mucin exhibited similar sensitivity and specificity. Positive immunoreactivity was associated significantly with tobacco use and the cytopathologic diagnoses of squamous metaplasia, atypia, or dysplasia. Conversely, no significant association was found between 4B5 immunoreactivity and age, gender, race, benign cytologic findings, frankly malignant cytologic findings, or stage of disease. The expression of 4B5 antigen in bronchial secretions from patients with bronchogenic carcinoma deserves additional evaluation as a potential marker of pulmonary carcinogenesis. PMID- 1515987 TI - Giant cell tumor of the skull. AB - BACKGROUND: Most giant cell tumors (GCT) occur at the ends of long bones. There is little information about GCT of the skull bones. METHODS: The authors reviewed the Mayo Clinic files, which contained 546 cases of GCT, and their own consultation files, which contained approximately 1500 cases. RESULTS: Eleven tumors occurred in the sphenoid bone with extension to the surrounding bones and structures in 8 patients. One tumor (in Paget's disease) occurred in the frontal bone, one tumor was in the occipital bone, and one tumor was in the temporal bone. There were 4 men and 11 women whose ages ranged from 8 to 78 years, with a mean of 36.5 years. Radiographic findings were not suggestive of a specific diagnosis, although the features were those of an aggressive lesion. Histologically, the tumors had features typical of GCT. However, a prominent spindle cell component was seen in five tumors. The initial treatment in all patients but one was intralesional excision that was as complete as possible. The last patient had a wide excision and had soft tissue recurrence at 1 year. This was excised and she was free of disease at 2.7 years. Three patients died, one in the immediate postoperative period and the other two at 1.6 and 4 years with progression of tumor. One patient had postoperative radiation therapy and was without evidence of disease for 2 years when he was lost to follow-up. The remaining 10 patients all had postoperative radiation therapy; 6 patients were alive without disease from 4 to 34 years. However, one of these six patients had a recurrence that was treated surgically with additional radiation. Four patients were alive with tumor from 2.1 to 26 years at the time of this report. CONCLUSIONS: GCT of the skull bones is rare but should be distinguished from giant cell reparative granuloma because of the tendency for progression. Surgical ablation (as complete as possible) and postoperative radiation therapy seem to be the treatment of choice for GCT of the skull bones. PMID- 1515988 TI - Angiosarcoma arising from malignant schwannoma in a patient with neurofibromatosis. AB - A 20-year-old man with von Recklinghausen disease had a right neck mass. Pathologic examination at excision showed angiosarcoma arising in a malignant schwannoma of the cervical brachial plexus. Comparison with previous reports revealed that angiosarcoma is a rare, highly aggressive sarcomatous element in malignant schwannoma arising in patients with neurofibromatosis (NF). PMID- 1515990 TI - Reverse targeting in a media-promoted breast cancer screening project. AB - BACKGROUND: The American Cancer Society has sponsored community-based, low-cost, Breast Cancer Detection Awareness Projects throughout the United States. The authors hypothesized that these projects tend to exclude minorities and women of lower socioeconomic status--groups with a higher incidence of late-stage disease. METHODS: A cross-sectional survey was performed of participants in the 1990 Breast Screening Project in Tampa, Florida. The demographic profile of participants was compared with that predicted by 1990 census data. RESULTS: There were 13,920 women who called phone banks for additional information. Of these, 13,215 were deemed eligible and 6640 completed mammographic screening. Forty percent of participants were having mammography for the first time. Comparisons with census data indicated that elderly people, members of minority groups, and women of lower educational levels were underrepresented. CONCLUSIONS: The results of this study support the concept that "reverse targeting" occurs with these breast cancer screening projects, and recommendations for recruiting underrepresented groups are given. PMID- 1515989 TI - Risk factors for failure of immediate breast reconstruction with prosthesis after total mastectomy for breast cancer. AB - BACKGROUND: Immediate breast reconstruction (IBR) after mastectomy represents a clear improvement in the quality of life of patients with breast cancer, but prosthesis removal is relatively frequent. Therefore, it is important to identify risk factors related to this removal. METHODS: A series of 142 patients treated with mastectomy and IBR at the Institut Gustave-Roussy between January 1976 and December 1988 were studied. Forty-seven had an in situ carcinoma, 93 an infiltrating carcinoma, and 2 a fibrosarcoma. IBR failures were defined as removal of the prosthesis, and early failures as removal during the first 7 weeks after IBR. RESULTS: The early failure rate was significantly higher in patients with invasive carcinomas or fibrosarcomas than patients with in situ carcinomas (12% versus 0%, P = 0.04). The risk of late IBR failure was significantly higher in patients who had received postoperative radiation therapy than patients who did not (P = 0.0002). However, this increased risk applied only to women in whom the chest wall was exposed to radiation because of a high risk of recurrence. CONCLUSION: It might be preferable to postpone breast reconstruction for patients with infiltrating breast carcinoma because early complications are not infrequent and could delay adjuvant chemotherapy. Late complications associated with chest wall irradiation could be avoided with the use of alternative techniques such as the transverse rectus abdominis myocutaneous (TRAM) flap procedure. PMID- 1515991 TI - Prognostic significance of DNA quantitation in stage D1 prostate carcinoma with the use of image analysis. AB - BACKGROUND: A characteristic feature of prostatic adenocarcinoma is its great variation in biologic behavior. This variation and the observation that most carcinomas are of intermediate grade make standard histologic grading of limited value in determining the prognosis of a patient. METHODS: DNA quantitation with the use of computer-assisted image analysis on Feulgen-stained nuclei was performed on the metastatic lymph nodes from patients with Stage D1 prostate carcinoma to determine whether ploidy was a useful predictor of survival or progression. The Gleason histologic score of the primary tumor, the number and extent of lymph node metastases, and the progression and survival intervals were documented. Treatment modalities included pelvic lymph node dissection, radical prostatectomy, external beam radiation therapy, and iodine 125 implantation. RESULTS: DNA ploidy quantitation showed that 65% (33 of 51) of cases were aneuploid, 2% (1 of 51) were tetraploid, and 33% (17 of 51) were in the diploid range. Progression to Stage D2 disease occurred in 76% of the patients with aneuploid cases and 53% of those with cases in the diploid range. CONCLUSION: There was a significant difference in progression between the two ploidy groups (Cox regression analysis, P less than 0.05). PMID- 1515992 TI - Hodgkin disease mortality in the United States: 1979-1988. AB - Mortality trends for Hodgkin disease in the United States were examined from 1979 to 1988 with the use of mortality data for multiple causes of death, which were obtained from the National Center for Health Statistics. A progressive decrease in the death rate from Hodgkin disease was observed over this period. The decrease in death rate was greatest among white patients. Patients who were 55 years or older had the highest death rate. Analysis by geographic region showed decreases in each of the regions, with no significant difference among groups of states with high and low incidences of acquired immune deficiency syndrome. However, the decrease in the South was approximately 35% greater than that in the North-east. In 1988 the most significant difference in death rates between male and female patients was in the 35-54-year age group, whereas a significant difference in death rates between white and black patients was seen only in patients who were 55 years of age or older. In summary, although there has been a significant reduction in deaths resulting from Hodgkin disease between 1979 and 1988, the decreases observed have varied between sexes and among age groups, racial groups, and geographic regions. PMID- 1515993 TI - Cancer incidence in the Puerto Rican-born population of Connecticut. AB - There are few published reports on cancer incidence in the Puerto Rican-born populations of the northeastern United States. In Connecticut, in the Puerto Rican-born population, which was of low socioeconomic status (i.e., 42% below the poverty level in the 1980 Census), the standardized incidence ratio (SIR) for all invasive cancers diagnosed in 1980-1986 was significantly reduced for female patients (SIR = 0.77) but not for male patients (SIR = 1.16), on the basis of expected numbers derived from incidence rates for the entire state of Connecticut. For female patients, only the SIR for cancers of the stomach, esophagus, and cervix were elevated significantly, whereas those for colorectal, lung, breast, and ovarian cancer were significantly reduced. For male patients, SIR were elevated significantly for cancer of the oral cavity, esophagus, and stomach and for leukemia, whereas none of the sites (including lung) had significantly reduced SIR. When incidence rates for Puerto Rico were used, the SIR for all sites combined was 1.99 (95% confidence interval = 1.78-2.22) for male patients but only 1.39 (95% confidence interval = 1.24-1.56) for female patients. These findings suggest sex differences in acculturation and lifestyle changes relevant to cancer risks in immigrants from Puerto Rico residing in Connecticut. Comparisons were made with cancer incidence and mortality data from other Puerto Rican immigrant populations. PMID- 1515994 TI - Hyperthermia enhances the inhibition of tumor growth by 1-(2-tetrahydrofuryl)-5 fluorouracil/uracil (1:4) in tumors in mice and humans. AB - The cytotoxicity of several antitumor drugs is enhanced by hyperthermia (HT). Using mouse Sarcoma-180 (S-180) tumors, the authors examined the effects of 5 fluorouracil (5-FU) and a combined oral preparation of 1-(2-tetrahydrofuryl)-5 fluorouracil (FT) and uracil in a molar ratio of 1:4 (UFT), in combination with HT. The antitumor effect of 5-FU was not enhanced significantly by HT. Growth inhibition by UFT plus HT was significantly greater than that by UFT alone, whereas inhibition by UFT alone was significantly greater than that by 5-FU. The intracellular metabolism of 5-FU and FT in whole homogenates of S-180 cells, human tumor cell lines (SC-2 and Lu-99), and five fresh human tumor tissues also was investigated. Conversion of FT to 5-FU, phosphorylation, and degradation of 5 FU were assayed with [3H]FT or [3H]5-FU, and the products were separated by thin layer chromatography. The conversion of FT to 5-FU and the phosphorylation of 5 FU were more rapid at 43 degrees C than at 37 degrees C, whereas the degradation of 5-FU to 2-fluoro-beta-alanine remained unchanged. This acceleration of the active metabolism of FT and 5-FU may be one explanation for the enhanced effect of UFT by HT. PMID- 1515995 TI - Familial mesothelioma. Details of 17 cases with histopathologic findings and mineral analysis. AB - Nine new cases of mesothelioma clustering in four families are described, and additional information is provided on four previously reported families. All of the members of these families had some exposure to asbestos. Diagnoses were confirmed histologically, and the relevance of the histologic pattern is discussed after the literature review. The lung mineral fiber burden was quantified in patients by transmission electron microscopic examination and energy-dispersive x-ray analysis, and this confirmed significant exposure to amphibole asbestos in all patients. Evidence supporting an increased incidence of mesothelioma in family members is discussed. PMID- 1515996 TI - Surgical treatment of thoracic esophageal carcinoma directly invading the lung. AB - BACKGROUND: The authors examined 63 patients with thoracic esophageal carcinoma directly invading the adjacent lung. Four of them had esophago-pulmonary fistulas. One patient received exploratory thoracotomy and exposure to radiation, and 62 underwent esophagectomy with mediastinal and abdominal lymph node dissection. A resection of the seized lung and the esophagus was performed in 39 patients (Group A), and 23 received esophagectomy with part of the tumor remaining intact (Group B). METHODS: The results of treatment were compared between the two groups. RESULTS: Operative blood loss, mortality, and complications in both groups showed no difference. The average number of dissected lymph nodes in Group A was significantly larger than that in Group B (P less than 0.01). Histologic examination revealed that 22 (56.4%) lesions in Group A invaded the pulmonary parenchyma, a finding that indicates the difficulty of gross diagnosis of tumor infiltration. Five-year survival rates for patients in Groups A and B were 21.1% and 8.7%, respectively. The survival curve for patients in Group A was significantly better than for those in Group B (P less than 0.05). CONCLUSIONS: Pulmonary resection and aggressive lymph node dissection are recommended for patients with esophageal carcinoma that invades the adjacent lung. PMID- 1515997 TI - Poorly differentiated medullary carcinoma of the stomach. AB - BACKGROUND: The biologic behavior of poorly differentiated medullary carcinoma of the stomach is unclear. METHODS: A clinicopathologic study on 74 poorly differentiated medullary carcinomas (PMC) and 73 nonmedullary carcinomas (NMC) of the stomach was done. PMC were defined as gastric carcinomas in which more than 50% of the tumor area contained poorly differentiated adenocarcinoma with no fibrous stroma. RESULTS: They were characterized by a location in the upper 33% of the stomach (49%), grossly expansive growth (69%), frequent vascular permeation (57%), and simultaneous liver metastasis (15%). Although the 5-year survival rate was similar for PMC and NMC, death of PMC was related more frequently to liver metastasis (47%) and less frequently to peritoneal dissemination (12%). The outcome of patients with PMC was influenced by frequent vascular permeation, extended lymph node metastasis, and simultaneous liver metastasis. CONCLUSIONS: These results indicate that PMC are characterized by expansive growth of the tumor and simultaneous or recurrent metastasis to the liver. Therefore, the biologic behavior of poorly differentiated medullary carcinoma is similar to that of well-differentiated carcinoma of the stomach. PMID- 1515998 TI - Mucin oligosaccharide biosynthesis in human colonic cancerous tissues and cell lines. AB - BACKGROUND: The Tn, sialosyl-Tn, and T antigens are carbohydrate-associated antigens that represent initial steps in mucin O-linked glycosylation. Previous immunohistochemical studies have shown that these three antigens are rarely, if ever, expressed in normal colonic mucosa; however, most colonic cancerous tissues express these structures. Little is known about the factors that control the expression of these antigens in colonic tissues or cell lines. One hypothesis is that cancers have increased levels of the glycosyltransferase activities responsible for synthesizing these antigens. METHODS: The current study analyzed antigen expression by immunohistochemistry and glycosyltransferase enzyme activities for Tn, sialosyl-Tn, and T antigens in colonic tissues and cell lines to (1) compare values between normal and cancerous tissues and (2) correlate these results with tumor stage, histologic findings, and location. RESULTS: All nine colonic cancer cell lines expressed Tn antigen; sialosyl-Tn and T antigens were expressed by the more mucin-producing cell lines. Sialosyl-Tn transferase activity was higher in the more mucinous cell lines; T transferase activity was higher in those with less mucin. In paired specimens of normal and cancerous tissues, levels of each of the three glycosyltransferases were similar. In cancerous tissues, enzyme activity did not correlate with tumor location, stage, or histologic type. There also was no correlation between glycosyltransferase activity and expression of the relevant antigen. CONCLUSIONS: Thus, because normal and malignant colonic tissues have comparable levels of Tn, sialosyl-Tn, and T glycosyltransferases, the absence of these antigens in normal mucosa apparently is related to other factors such as antigen masking. PMID- 1515999 TI - Antipyrine metabolism in patients with liver metastases from colorectal cancer. AB - BACKGROUND: The influence of cancer on antipyrine metabolism is under debate. METHODS: To assess the functional activity of a liver with solid metastases from primary colorectal cancer, antipyrine metabolism was studied after the drug was administered orally (18 mg/kg body weight) to 55 healthy volunteers, 62 patients with well-compensated cirrhosis, and 42 patients with small (Class A) or massive (Class B) metastatic liver involvement. RESULTS: In patients with cancer, antipyrine clearance (0.472 +/- 0.177 ml/min/kg) was similar to that in healthy volunteers (0.456 +/- 0.198 ml/min/kg) and significantly higher than in those with cirrhosis (0.259 +/- 0.17 ml/min/kg, P less than 0.001). There was no difference in antipyrine pharmacokinetics between Class A and B involvement. In the entire population, antipyrine clearance was correlated with serum albumin levels (r = 0.294, P = 0.0002) and prothrombin activity (r = 0.416, P = 0.001). This positive correlation was not present when only the neoplastic group was considered. No correlation was found between antipyrine clearance and alkaline phosphatase levels. In patients with cancer, no relationship was found between antipyrine clearance and carcinoembryonic antigen and lactic dehydrogenase levels. CONCLUSIONS: These results show that patients with livers largely replaced by solid metastases are able to metabolize antipyrine to the same extent as healthy subjects. PMID- 1516000 TI - Carcinoma of the gallbladder. Histologic types, stage of disease, grade, and survival rates. AB - Data on patients with gallbladder cancer listed in the Surveillance, Epidemiology, and End Results (SEER) Program of the National Cancer Institute were reviewed. Between 1977 and 1986, 3038 patients were recorded in the Program. Histologic grade, histologic type, stage of disease, and vascular invasion were correlated with outcome. Compared with all other histologic types of cancer, papillary carcinomas had the most favorable prognosis. The 2-year survival rate for patients with papillary carcinoma was 47%. A correlation with survival existed between grade, stage of disease, and vascular invasion. The study confirmed that cancers of the gallbladder occur more often in older age groups and are more common in women. Almost 40% of cases are found at an advanced stage. For patients whose enolase tumor was limited to the gallbladder at the time of surgery, the 2-year survival rate was 45% and the 5-year rate was 32%. PMID- 1516001 TI - Carcinoma of the extrahepatic bile ducts. Histologic types, stage of disease, grade, and survival rates. AB - Data on patients with extrahepatic bile duct carcinomas recorded in the Surveillance, Epidemiology, and End Results (SEER) Program of the National Cancer Institute were reviewed. We analyzed the records of 1766 patients reported during a 10-year period (1977-1986). These tumors occurred primarily in older age groups and were slightly more common in males. Histologic grade, histologic types, and stage of disease are useful prognostic indicators. The 5-year survival rate for patients with Stage I disease was 11%. Although carcinomas of the extrahepatic bile ducts are better differentiated than carcinomas arising in the gallbladder, they have a less favorable prognosis. PMID- 1516002 TI - The mucus-hypersecreting tumor of the pancreas. Development and extension visualized by three-dimensional computerized mapping. AB - BACKGROUND: Mucus-hypersecreting tumor of the pancreas appears as dilated ducts and cystic spaces filled with mucus. To determine where such tumors arise and how they extend, computer-aided three-dimensional reconstruction was done of the ductal system. This also was used to visualize the spatial relationships among epithelial hyperplasia, dysplasia, and carcinoma in situ (CIS). METHODS: Surgically removed pancreases were studied from 12 patients with mucus hypersecreting tumors. The specimens were fixed in buffered formaldehyde solution 10%, embedded in paraffin and semiserially sectioned at 3 microns at an interval of 60 microns. The ductal contours were differentiated among ducts lined by ordinary epithelia, hyperplastic epithelia, dysplastic cells, or CIS and were inputted into a computer system that integrated a three-dimensional image of ducts in the display. RESULTS AND CONCLUSIONS: (1) The tumors arose in the main pancreatic duct or its subbranches, and the cysts corresponded to segments expanded by the superficial growth of tumor cells; (2) areas of CIS arose in zones of preceding dysplasia, suggesting a dysplasia-carcinoma sequence; and (3) dysplastic or cancerous cells often extended intraductally over the dilated segments of ducts. PMID- 1516003 TI - The establishment of an interleukin-6-dependent myeloma cell line (FLAM-76) carrying t(11;14)(q13;q32) chromosome abnormality from an aggressive nonsecretory plasma cell leukemia. AB - A new myeloma cell line designated FLAM-76 was established from a patient with an aggressive nonsecretory plasma cell leukemia. The cell line exhibited morphologic features of flaming cells and contained an abundant eosinophilic cytoplasm with many dilated cisternae of rough endoplasmic reticulum. FLAM-76 cells were positive for cytoplasmic kappa (kapp)-type immunoglobulin but did not secrete it into the culture medium. The cells proliferated in the presence of exogenous interleukin-6 (IL-6) and more than 800 pg/ml of IL-6 was necessary for their continuous growth. The cells did not grow without IL-6, and they did not produce IL-6. Thus, the growth of FLAM-76 appeared to be regulated by the paracrine mechanism of IL-6. Alpha-interferon (alpha-IFN) inhibited the IL-6-dependent growth of FLAM-76 in doses greater than 1000 U/ml. FLAM-76 cells expressed CD38 (OKT10) and cell adhesion-associated antigens such as CD44 and CD54 (ICAM-1). Chromosome analysis revealed FLAM-76 to have a hypodiploid chromosome constitution with t(11;14)(q13;q32) abnormality, which frequently is seen in neoplasms of B-cell origin. Immunoglobulin (JH and Ck) gene rearrangement (but no BCL-1 gene rearrangement) was found in this cell line. PMID- 1516004 TI - Acute leukemia arising from a myelodysplastic syndrome after long-term administration of iproplatin. AB - BACKGROUND: Iproplatin (cis-dichloro-transdihydroxybis-isopropylamine platinum IV; CHIP) is a second generation cisplatin derivative that was developed to retain the antineoplastic effect of cisplatin with fewer toxic effects. Early clinical studies showed moderate activity in some neoplasms, with disappointing results in tumors of the lower gastrointestinal tract. Myelosuppression was the dose-limiting toxic effect in the acute setting. METHODS: The authors report a patient with metastatic adenocarcinoma of the colon who received long-term therapy with CHIP. RESULTS: The patient achieved complete remission of disease after prolonged treatment with CHIP. The patient subsequently had a myelodysplastic syndrome that rapidly transformed to acute myelogenous leukemia. CONCLUSIONS: Acute leukemia may represent a late complication of CHIP therapy. PMID- 1516005 TI - Testicular relapse in adult acute myelogenous leukemia. AB - Testicular relapse (TR) in adult acute myelogenous leukemia (AML) is uncommon, occurring in only 1-2% of patients with bone marrow relapse. TR in the absence of systemic relapse has been reported previously in 2 adults and 12 children, of which 67% were monocytic variants of AML. This article presents the case of a 29 year-old man with AML that relapsed in his testicle without evidence of bone marrow relapse. This patient and the two previously mentioned adults experienced bone marrow relapse within 2 months and died within 7 months of their TR. TR in adult myelogenous leukemia should be considered a harbinger of systemic relapse and suggests a need for aggressive local and systemic therapy. PMID- 1516006 TI - Erythrocyte sedimentation rate as a tumor marker in human prostatic cancer. An analysis of prognostic factors in 300 population-based consecutive cases. AB - BACKGROUND: The natural history of prostatic cancer is variable. Our knowledge of prognostic factors is limited; therefore, research is needed. METHODS: The cases of 300 population-based consecutive patients with a diagnosis of cancer of the prostate were analyzed regarding different prognostic factors (but with special reference to the erythrocyte sedimentation rate [ESR]). RESULTS: After a mean observation time of 100 months, M category, ESR, grade, performance status, hemoglobin level, and T category were found to correlate with disease-specific death using multivariate analysis. The variables correlating with progression in the multivariate model were M category, ESR, T category, grade, treatment, and age. Patients treated with estrogen had a significantly lower risk (relative hazard, 0.3) of relapse. ESR was highly statistically significant (P less than 0.0001) as a prognostic factor. With the variable in linear form, a 20-mm/h higher level suggested a 29% increased risk, on average, for dying of prostatic cancer (using a best-fit multivariate model). However, the relationship was not linear. After correcting for the effect of other factors, the risk for dying of prostatic cancer was lowest when the ESR was 40-50 mm/h and highest when its values were highest. CONCLUSIONS: ESR is an indicator of increased risk of progression and death in prostatic cancer. Other prognostic factors such as M and T categories, grade, performance status, hemoglobin level, and age currently are more important when planning treatment. It is possible that the ESR reflects aspects of tumor-host relationship and that both a low and high ESR are markers for patients with receding host defence mechanism. PMID- 1516007 TI - Outcome of renal transplantation or dialysis in patients with a history of renal cancer. AB - BACKGROUND: Therapeutic options for patients with bilateral renal cancer or cancer in a solitary kidney are limited to partial nephrectomy or bilateral radical nephrectomy with subsequent renal transplantation or dialysis. The outcome after partial nephrectomy is well documented, but few reports discuss the long-term survival of patients receiving chronic dialysis or after renal transplantation. Information regarding the long-term prognosis for these patients is important when deciding on the appropriate treatment. METHODS: The authors retrospectively evaluated the long-term prognosis of 23 patients who lost renal function because of surgery for renal cell carcinoma or Wilms' tumor between 1970 and 1990. RESULTS: Twelve patients had renal transplantation (Tx group), and 11 had chronic dialysis (DS group). In the Tx group, four patients had Wilms' tumor and eight had renal cell carcinoma (Stage I, 5 patients; Stage II, 2 patients; Stage III, 1 patient). In the DS group, three patients had Wilms' tumor, and eight had renal cell carcinoma (Stage I, 5 patients; Stage III, 2 patients; Stage IV, 1 patient). Unexpectedly, 9 of 11 (82%) patients from the DS group died of cancer, compared with 1 of 12 (8%) patients who had transplantation (P = 0.0133) despite comparable stages of renal cell carcinoma and Wilms' tumor in the two groups. CONCLUSIONS: For patients who have had bilateral nephrectomy or removal of a solitary kidney, the authors recommend waiting at least 12 months, during which time the patient receives dialysis, before proceeding with transplantation if there is no evidence of recurrent tumor. PMID- 1516008 TI - Long-term survival of 1986 patients with intracranial meningioma diagnosed from 1953 to 1984 in Finland. Comparison of the observed and expected survival rates in a population-based series. AB - Intracranial meningioma was diagnosed and histologically verified in 1986 patients, 597 men and 1389 women, between 1953 and 1984 in Finland. The closing date of this survival study was December 31, 1987, and the follow-up was complete. Meningiomas, usually slowly growing and surgically curable benign tumors, caused considerable short-term mortality, with a relative survival rate (RSR) of 83% at 1 year, and slight but continual long-term mortality, with RSR of 71% at 15 years. From 1979 to 1984, when computed tomography (CT) was available, the mortality at 3 months for the patients who had surgical procedures was 2% in those younger than 45 years and 10% in those older than 64 years; patients who did not have operations had 1-year mortality of 61%. The short-term and long-term excess mortalities are associated significantly with old age, no surgical procedure, and the period of diagnosis; the long-term excess mortality also is associated with male gender. PMID- 1516009 TI - Multiple thyroid involvement (intraglandular metastasis) in papillary thyroid carcinoma. A clinicopathologic study of 105 consecutive patients. AB - Multiple thyroid involvement (MTI) in papillary thyroid carcinoma was clinicopathologically studied in 105 non-selected, consecutive patients. Whole thyroids resected by total thyroidectomy were sectioned at intervals of 2-3 mm (mean number of slices per gland, 19.2) and histologically reviewed. The intraglandular cancer foci, other than the tumor regarded as the primary focus, were demonstrated in 82 (78.1%) of 105 patients. The foci were usually small (less than 4 mm) and were not accompanied by sclerotic fibrous stroma or by a fibrous capsule. These small foci were distributed around the primary lesion and also were found frequently (61.0%) in the opposite lobe as bilateral disease. In the opposite lobe, a similar incidence (approximately 30%) of disease was obtained in each of the three parts (upper, middle, and lower). The mean number of foci in patients with MTI was statistically correlated to age, the presence of lymph node metastases, and the presence of solid areas or psammoma bodies in the primary tumor. It was concluded that MTI could be regarded as one of the most striking and important biologic characteristics of papillary thyroid carcinoma. PMID- 1516010 TI - Phase II trial of 4'-0-tetrahydropyranyladriamycin (pirarubicin) in head and neck carcinoma. AB - BACKGROUND: 4'-0-tetrahydropyranyladriamycin (Pirarubicin, Meiji Seika (USA) Inc., New York, NY) may be less toxic than doxorubicin. METHODS: A Phase II trial of Pirarubicin was done in 26 patients who had not previously had chemotherapy and who had measurable and incurable head and neck carcinoma. All patients received an intravenous bolus dose of 60 mg/m2 Pirarubicin in the first cycle without any prophylactic antiemetic. The cycles were repeated every 3 weeks. Based on tumor response, nadir counts, or complications of myelosuppression, the doses were escalated or de-escalated by 10 mg/m2, if necessary, in the second cycle to achieve mild leukopenia (3000-4000 leukocytes/microliters). RESULTS: Leukopenia was mild, moderate (2000-2999 leukocytes/microliters), severe (1000 1999 leukocytes/microliters), and life threatening (less than 1000 leukocytes/microliters) in 13%, 31%, 27%, and 9% of the first two courses, respectively. The median interval to nadir leukopenia was 13 days (range, 7-21 days), with a median of 8 days (range, 5-13 days) to recover to normal. One patient with a leukocyte count of 800/microliters and an absolute granulocyte count (AGC) of 488/microliters died of sepsis 15 days after the first course. All patients had at least one course that resulted in leukopenia. One episode each of mild (100,000-150,000 platelets/microliters) and severe (25,000-49,999 platelets/microliters) thrombocytopenia occurred in the first two courses. Leukocyte, granulocyte, and platelet counts were not done routinely after the second cycle. Six patients who received four or more courses with cumulative doses of 310, 610, 340, 260, 660, and 550 mg/m2 had decrements of 0%, 1%, 7%, 10%, 12%, and 13%, respectively, in radionuclide left ventricular ejection fraction (LVEF). All other toxic effects were mild. CONCLUSIONS: In the 24 patients with disease evaluable for response to Pirarubicin therapy, 1 had a complete response that lasted 5 months and 4 had a partial response of 2, 3, 6, and 8 months. The median survival time in patients with disease that responded to Pirarubicin therapy was 27 months; in patients with disease that did not respond to Pirarubicin therapy, the median survival time was 4 months, and in the total cohort, it was 5 months. Pirarubicin was well tolerated and was an active agent in head and neck squamous cell carcinoma. PMID- 1516011 TI - Paraneoplastic myelopathy at diagnosis in a patient with pathologic stage 1A Hodgkin disease. AB - The case of a patient with pathologic Stage 1A Hodgkin disease is reported in whom subacute paraneoplastic myelopathy developed before treatment. Myelography, computed tomography, magnetic resonance imaging, and lumbar puncture examination showed no evidence of central nervous system involvement. The patient was treated with combination chemotherapy (to avoid spinal cord exposure to radiation) without neurologic improvement. The patient's neurologic condition responded well to intrathecal dexamethasone. PMID- 1516012 TI - The role of gastric stasis in tumor-induced anorexia in rats. AB - BACKGROUND: The current study was undertaken to determine if changes in gastric emptying contribute to tumor-induced anorexia. METHODS: Rats were implanted with the Walker 256 carcinoma, and food intake was measured daily. On days 0, 8, and 15, the rats were fasted overnight, gavage fed a bolus of liquid food, and residual gastric contents were measured 3 hours later. RESULTS: Tumor growth was associated with a progressive decline in voluntary food intake. When the rats were gavage fed 2.5 or 7 ml of liquid food, the percent of gastric contents cleared in 3 hours was unchanged with tumor growth. CONCLUSIONS: Changes in gastric emptying did not contribute to decreased food intake with growth of the Walker 256 in rats. PMID- 1516013 TI - Radiation recall associated with vinblastine in a patient treated for Kaposi sarcoma related to acquired immune deficiency syndrome. AB - A 34-year-old white man with the human immunodeficiency virus infection had a large Kaposi sarcoma lesion of his foot. This was treated with local radiation therapy consisting of 2700 rads administered in 15 fractions during a period of 28 days. Ten months later, the patient had painful disseminated Kaposi sarcoma and was treated with a 10 mg/m2 dose of intravenous vinblastine. Forty-eight hours after receiving the chemotherapy, the patient had an area of localized painful erythema develop, swelling, and vesicular eruption over the previous site of radiation therapy. This was healed by the fifth day after chemotherapy. No additional vinblastine was administered. Radiation recall occurring in a patient with significant immunosuppression (CD4 lymphocytes, 30 cells/microliters) possibly suggests that the tissue response is not a lymphocyte-mediated event. PMID- 1516014 TI - Mediastinoscopy incisional metastasis. A radiotherapeutic approach. AB - Tumor seeding of the mediastinoscopy tract has been described. Although it is a rare occurrence, it can present the radiation oncologist with a therapeutic dilemma. Two cases of mediastinoscopy scar recurrences are reported. Their response to treatment and a review of previous cases are included. PMID- 1516015 TI - Pain in ambulatory patients with lung or colon cancer. Prevalence, characteristics, and effect. AB - BACKGROUND: Few studies have evaluated the epidemiology and effect of pain in ambulatory patients with cancer who are undergoing active therapy. This information is needed to develop strategies for supportive care in this population. METHODS: The prevalence and characteristics of pain were determined in a prospective survey of ambulatory patients with lung or colon cancer. To reduce bias and acquire comprehensive information, the methodology used face-to face interviews by trained quality assurance analysts, a multifaceted assessment instrument, and multivariate statistical analysis. RESULTS: In a telephone interview, "persistent or frequent" pain during the previous 2 weeks was reported by 57 of 145 (39.3%) patients with lung cancer and 52 of 181 (28.7%) patients with colon cancer; 91 of these patients (47 lung and 44 colon) were interviewed in detail. All patients had excellent performance status, and with the exception of pain location, there were no significant differences between the two tumor types. One-third of the patients had more than one discrete pain. Median pain duration was 4 weeks (range, less than 1 week-468 weeks), and average pain intensity was moderate. Approximately 90% of patients experienced pain more than 25% of the time. Pain interfered moderately or more with general activity and work in approximately half of the patients; more than half reported moderate or greater pain interference in sleep, mood, and enjoyment of life. Multiple regression analysis revealed that the daily frequency of pain, the intensity of the worst pain, the score on a mood scale, and the frequency of the worst pain accounted for 58.7% of the variance in average pain intensity. Likewise, 52.1% of the variance in a derived measure of pain interference in function was explained by the mood score, frequency of the worst pain, number of pains, and pain intensity. CONCLUSIONS: These data indicate that pain is prevalent among well functioning ambulatory patients and substantially compromises function in approximately half of the patients who experience it. Pain is a complex symptom; aspects other than intensity, such as frequency, strongly influence its effect. PMID- 1516016 TI - Disseminated neuroblastoma (stage IV and IV-S) in the first year of life. Outcome related to age and stage. Italian Cooperative Group on Neuroblastoma. AB - BACKGROUND: Infants (age 0-11 months) with disseminated neuroblastoma are known to have a better prognosis than older children with the disease, but there is little information regarding factors that influence the outcome of the disease in these patients. METHODS: The authors report a series of 110 infants with disseminated neuroblastoma with disease diagnosed between March 1976 and February 1991 in 21 institutions participating in the Italian Cooperative Group on Neuroblastoma (ICGNB). Of the 110 infants, 34 had Stage IV disease, and 76 had Stage IV-S disease. RESULTS: The 5-year survival probability was 77% for all patients, 71% for those with Stage IV disease, and 81% for those with Stage IV-S disease. Of the 34 infants with Stage IV disease, the 9 who were 5 months or younger at the time of disease diagnosis are all alive (1 with active disease) at 7-143 months after diagnosis, whereas of the 25 infants who were 6-11 months of age at the time of disease diagnosis, 10 have died. Of the 76 infants with Stage IV-S disease, 12/64 who were 5 months of age or younger at the time of disease diagnosis died (mostly of massive hepatomegaly); 9 of these deaths occurred in infants with disease diagnosed before they were 2 months old, whereas 1 death occurred in the 12 infants with disease diagnosed when they were 6-11 months old. Four infants with Stage IV-S disease achieved complete disease remission and subsequently had relapse of disease. High levels of serum LDH and low urinary excretion of vanillylmandelic acid were associated with worse prognosis. CONCLUSIONS: The authors suggest that infants older than 6 months of age who have Stage IV disease require aggressive therapy. For infants with disease diagnosed before they are 2 months old, Stage IV-S disease may have a worse prognosis than Stage IV disease. PMID- 1516017 TI - Tinea corporis confined to irradiated skin. Radiation port dermatophytosis. AB - BACKGROUND: Radiation port dermatophytosis (RPD) is an uncommon condition in which patients receiving radiation therapy concurrently have tinea corporis that is confined primarily to the irradiated skin. METHODS: The case of a 33-year-old man is reported who was receiving cobalt-60 radiation therapy for a nasopharyngeal carcinoma. During therapy, a dermatophyte infection developed in the treated field. RESULTS: Including this patient, there have been only three cases of RPD reported in the world literature. The clinical characteristics of patients with RPD are reviewed. The diagnosis, management, and pathogenesis of this condition are discussed. CONCLUSIONS: Because the cutaneous manifestations of RPD may be misinterpreted clinically as acute radiation-induced dermatitis, this condition may be more prevalent than the paucity of published reports suggests. PMID- 1516018 TI - An atypical myeloproliferative disorder with high thrombotic risk and slow disease progression. PMID- 1516019 TI - An atypical myeloproliferative disorder with high thrombotic risk and slow disease progression. PMID- 1516020 TI - The effects of surgical treatment on survival and local recurrence of cutaneous malignant melanoma. PMID- 1516021 TI - The integration of molecular genetics into cancer management. AB - Many of the phenotypes of cancer cells and tumors can now be traced to specific mutations in the genomes of these cells. These mutations may activate oncogenes, providing mitogenic stimulus to these cells. Alternatively, they may inactivate tumor-suppressor genes, relieving growth-inhibiting constraints placed on these cells. These genetic lesions together provide many of the explanations for the deregulated growth of tumor cells. PMID- 1516022 TI - Cytogenetics of epithelial malignant lesions. AB - Chromosomal abnormalities have been believed to be responsible for neoplastic transformation and tumor growth for a long time. The confirming observations are of two types: (1) primary cytogenetic alterations that are responsible for tumor initiation and (2) secondary abnormalities that are acquired late and are associated with tumor growth, heterogeneity, and metastasis. Primary chromosomal abnormalities (such as the 13q deletion in retinoblastoma, 11p deletion in Wilms' tumor, 3p anomalies in renal cell carcinoma, and 5q deletion in colorectal carcinomas) first were identified in lymphocyte cultures as constitutional defects. Later, similar types of defects were observed as tumor-specific aberrations from patients whose lymphocytes otherwise had normal chromosomes. Recently, it has become clear that classes of known cancer-related genes (dominant protooncogenes and recessive tumor-suppressor or anti-oncogenes) are located at those hot spots that are involved in neoplasia-associated chromosomal alterations. In breast carcinoma, such a specific chromosomal alteration has not been identified conclusively in lymphocyte cultures, although chromosome 1 alterations have been observed in cell lines, directly processed effusions, and primary breast tumors. Lymphocyte cultures; primary tumors; and established cell lines from breast carcinomas, colorectal carcinomas, and renal cell carcinomas were analyzed to identify (1) primary chromosomal alterations precisely and (2) secondary cytogenetic defects that are associated with these most common solid adult neoplasms. Peripheral blood analysis indicated that chromosomes 1, 17, and 18 in breast carcinomas; chromosomes 3 and 14 in renal cell carcinomas; and chromosomes 5, 12, and 17 in colorectal carcinomas were involved nonrandomly in structural anomalies in a small number of lymphocyte cells (1-4%). These chromosomal aberrations were considered primary defects because of their involvement as marker formations in tumor cells; other structural and numeric abnormalities also were found. These results indicate that lymphocyte chromosomal analysis might identify those at high risk for breast, colorectal, and renal cell carcinomas, among other malignant lesions. Such identifications could facilitate early selection for primary and secondary cancer prevention or interventional trials. PMID- 1516023 TI - The role of molecular techniques in the clinical management of leukemia. Lessons from the Philadelphia chromosome. AB - The Philadelphia chromosome (Ph1) was the first genetic change to be associated consistently with leukemia, and it is one of the best understood on the molecular level. Because of this, it is an excellent model to investigate the application of molecular techniques to the clinical setting. These techniques are reviewed as are their clinical use in chronic myelogenous leukemia (CML), acute lymphoblastic leukemia (ALL), and transplantation. The Ph1 is caused by the fusion of two genes on chromosomes 9 and 22, resulting in the BCR-ABL fusion gene. This new gene is believed to be the cause of these Ph1-positive leukemias. The ability to detect the BCR-ABL fusion gene evolved from cytogenetic detection to Southern blot analysis, and now includes sophisticated techniques such as polymerase chain reaction (PCR) methods and pulsed-field gels. Diagnosis of the BCR-ABL fusion gene by Southern blot detection of bcr genetic rearrangements is the prototype of molecular cancer diagnosis. The sensitivity and clinical uses of this test are reviewed, especially its application to monitoring the response to treatment. PCR methods enable the researcher to detect 1 CML cell in a population of 10(5) cells. Clinical experience with PCR, especially in transplantation medicine, is providing a better understanding of the meaning of the terms "remission" and "cure." Newer techniques using fluorescent in situ hybridization have considerable potential for BCR-ABL detection, but no clinical experience has been gained with these techniques currently. The diagnosis of the BCR-ABL fusion gene in ALL has important clinical implications because it is the most common molecular genetic change in adult ALL and is associated with short remissions and poor outcome in all age groups. Diagnosis of the BCR-ABL fusion in ALL is difficult because the molecular findings are more heterogeneous than they are in CML. The methods available and their accuracy and sensitivity are compared. A review of their clinical impact is included. PMID- 1516024 TI - Cytogenetic analysis in the diagnosis of acute leukemia. AB - Acute leukemias are characterized by acquired genetic rearrangements that, in most cases, can be detected by cytogenetic methods as clonal chromosomal abnormalities. Whereas primary abnormalities contribute to the establishment of the leukemia and often are seen as solitary changes, secondary aberrations accrue during clonal evolution. Both abnormalities are nonrandom in distribution. The pattern differs between acute lymphocytic leukemia (ALL) and acute nonlymphocytic leukemia (ANLL) and from subtype to subtype. Some abnormalities are so characteristic as to be virtually pathognomonic for particular types of leukemia. The importance of cytogenetic characterization of leukemias is thus two-fold. First, the recurrent aberrations provide insight into the pathogenetic mechanisms that are operative. They pinpoint areas of the human genome that carry genes or regulatory sequences whose function is disrupted in neoplastic cells. Second, even before the long-term goal of a more fundamental understanding of the neoplastic process is reached, the cytogenetic aberrations have direct clinical importance. The finding of an acquired clonal chromosomal abnormality in hematopoietic cells identifies the presence of a neoplastic disease. The aberration profile may reveal whether the patient has ALL or ANLL and which subtype it is. Remission and relapse can be monitored by cytogenetic analyses. Finally, the karyotypic pattern is an independent prognostic parameter that should be considered when the choice of therapy is made. PMID- 1516025 TI - The clinical significance of antigen receptor gene rearrangements in lymphoid neoplasia. PMID- 1516026 TI - Nutrition and colorectal cancer. AB - Environmental and genetic factors play an important role in the cause and pathogenesis of colorectal cancer. In addition to nutritional aspects, other environmental factors include physical exercise, energy intake, obesity, and parity. Dietary components currently under study are dietary fiber, fat, fruits, vegetables, and calcium. Intermediate markers of colonic proliferation, including bromodeoxyuridine and proliferating cell nuclear antigen incorporation, are being used to evaluate the response of the colonic epithelium to putative chemopreventative agents. PMID- 1516027 TI - Genetic alterations in the adenoma--carcinoma sequence. AB - Tumorigenesis is thought to be a multistep process in which genetic alterations accumulate, ultimately producing the neoplastic phenotype. A model was proposed to explain the genetic basis of colorectal neoplasia that included several salient features. First, colorectal tumors appear to occur as a result of the mutational activation of oncogenes coupled with the inactivation of tumor suppressor genes. Second, mutations in at least four or five genes are required to produce a malignant tumor. Third, although the genetic alterations often occur in a preferred sequence, the total accumulation of changes, rather than their chronologic order of appearance, is responsible for determining the tumor's biologic properties. Several different genetic alterations were identified that occur during colorectal tumorigenesis. Activational mutation of the ras oncogene was found in approximately 50% of colonic carcinomas and in a similar percentage of intermediate-stage and late-stage adenomas. Allelic deletions were discovered of specific portions of chromosomes 5, 17, and 18, which presumably harbor tumor suppressor genes. The target of allelic loss events on chromosome 17 has been shown to be the p53 gene, which is mutated, not only in colonic cancer, but also in a large percentage of other human solid tumors. The gene dcc recently was identified; this candidate tumor-suppressor gene on chromosome 18 appears to be altered in colorectal carcinomas. The protein encoded by the dcc gene has significant sequence similarity to neural cell adhesion molecules and other related cell-surface glycoproteins. By mediating cell-cell and cell-substrate interactions, this class of molecules may have important functions in mediating cell growth and differentiation. Alterations of the dcc gene may interfere with maintenance of these controls and thus may play a role in the pathogenesis of colorectal neoplasia. Another candidate tumor-suppressor gene also was identified on chromosome 5, mcc (for mutated in colorectal cancers). The mcc genetic alterations include one tumor with somatic rearrangement of one mcc allele and several tumors with somatically acquired point mutations in the coding region. Studies currently are ongoing to (1) identify additional tumor-suppressor gene candidates, (2) increase our understanding of normal tumor-suppressor gene function, and (3) demonstrate the functional tumor-suppressor ability of these genes both in vivo and in vitro. PMID- 1516028 TI - Current status of adjuvant chemotherapy for colorectal cancer. Can molecular markers play a role in predicting prognosis? AB - BACKGROUND: Recent clinical trials establish a beneficial effect for adjuvant chemotherapy after surgical resection of the primary tumor (1) as single treatment for patients with colonic cancer and (2) combined with radiation therapy for patients with rectal cancer. Because adjuvant chemotherapy is not universally effective and is associated with toxicity and some degree of risk, it would be desirable to supplement standard pathologic staging criteria to define more precisely the subset of patients at high risk for tumor recurrence who would benefit most from adjuvant therapy. Tumor cell DNA content and cell proliferation measured by flow cytometry were identified as important and independent prognostic factors for patients undergoing curative resection of colorectal cancer. Basic laboratory investigations show a series of more specific molecular and genetic abnormalities that might provide better prognostic discrimination. Recent molecular studies suggest that the process of tumorigenesis in colorectal cancer proceeds through a series of genetic alterations that include both dominant and recessive protooncogenes. Characterization of these molecular genetic abnormalities may provide valuable prognostic information for use in patient management. METHODS: Allelic loss was studied for chromosomes 5, 17, and 18, and immunohistochemical analysis was done of the p53 protein product in tumors from 91 patients with colorectal cancer. RESULTS: Preliminary analysis of disease-free survival after surgical resection in 60 patients with Dukes' B or C tumors suggests a poorer prognosis associated with allelic loss on chromosome 18q (P = 0.08). CONCLUSIONS: Additional studies involving a much larger population of patients with Dukes' B and C colorectal cancer are needed to define the true prognostic significance of these molecular markers. PMID- 1516029 TI - Familial versus sporadic breast cancer. AB - BACKGROUND: Studies comparing patients with familial and sporadic breast cancer have indicated that a family history of the disease can increase a woman's risk for having the disease twofold to threefold and that patients with familial breast cancer have a younger age at diagnosis and have a higher frequency of bilateral disease than those with sporadic breast cancer. Also, at least four types of breast cancers have been shown to be inherited. These findings led to the hypothesis that familial and sporadic breast cancer are the consequence of two biologically distinct mechanisms. METHODS: A two-step mutation model proposed by Knudson in 1971 provides a link between the molecular mechanisms underlying familial and sporadic breast cancer. According to this model, both cancers involve the same genomic change in homologous chromosomes. The only difference is that the first mutation is inherited and the second is somatic in familial cancer, whereas in sporadic cancer both mutations are somatic. Mutation is used in a broad sense and refers to either a point mutation at a specific locus or the loss of a locus by deletion or nondysfunction. RESULTS: This model has been shown to apply to several childhood and adult cancers, including breast cancer. Based on this model, patients with familial breast cancer will have their disease earlier in life and will have more bilateral cancer than patients with sporadic breast cancer. Moreover, the two types of patients should show no differences in clinicopathologic characteristics because both types involve the same genomic change and the pathogenesis of both types should be the same, thus arguing against the early hypothesis that patients with familial and sporadic breast cancer are the consequence of biologically distinct mechanisms. CONCLUSIONS: Breast cancer appears to involve the cumulative effect of several genetic lesions involving the activation of oncogenes and the inactivation of tumor-suppressor genes. Which genes are involved specifically as causative factors of breast cancer (the inherited gene or genes) and which are important somatically in its continued development and progression (oncogenes and tumor-suppressor genes) requires additional study. PMID- 1516030 TI - Genetic predisposition to breast cancer. AB - Breast cancer is the most common cancer among American women. Because metastatic breast cancer is an incurable disease, efforts to decrease breast cancer mortality have focused on early detection and improved treatment. Identification and analysis of a specific genetic susceptibility could permit detection of susceptible women and greatly increase the understanding of the initial step that eventually leads to cancer. Because susceptibility loci have been recognized as sites that often are altered during tumor progression, the identification and cloning of such loci could be important in developing cancer therapies. In this article, the progress being made in segregation analysis, linkage analysis, and cloning of breast cancer susceptibility loci is reviewed. The evidence for genetic inheritance is most consistent with dominant inheritance for at least three major susceptibility loci. Proliferative breast disease has been hypothesized to be an inherited lesion in breast cancer kindreds with both premenopausal and postmenopausal probands. Currently, there are many genetic markers for mapping the human genome. Technologic advances have progressed from restriction fragment length polymorphisms to highly polymorphic markers. Using this technology, breast cancer susceptibility in some kindreds with an early onset has been shown to be linked to chromosome 17q. Gene isolation eventually will follow with an increased understanding of the percentage of breast cancer cases that are a result of this genetic locus. Li-Fraumeni syndrome, which often is expressed as breast cancer, is due to mutations in the p53 gene. Characterization of the syndrome and its relationship to the altered gene should proceed rapidly. There is also a group of families exhibiting a genetic susceptibility that is not due to either of these loci. Together, these findings indicate that there are at least three separate major loci segregating for breast cancer susceptibility. With the current initiative to map and sequence the entire human genome and the advances that recently have been reported, a detailed molecular understanding of breast cancer predisposition can be envisaged. PMID- 1516031 TI - Prognostic factors. Stage and receptor status in breast cancer. AB - BACKGROUND: Anatomic and biologic indicators of prognosis provide the bases for management of patients with cancer of the breast. Combinations of these indicators are potentially more accurate than any alone. This review was undertaken to evaluate the prognostic relationship between stage and steroid hormone receptors. METHODS: The literature was reviewed relative to the influences of tumor size, axillary metastases, and tumor estrogen receptors on the survival of patients with cancer of the breast. RESULTS: Axillary node status is of primary importance as a predictor of recurrence and survival. Tumor size has only a secondary influence, but is prognostically useful in the absence of metastases. Estrogen and progesterone receptors provide prognostic information that is independent of axillary stage, but the influence is weak, often transient, and attributable at least partly to a close association with other biologic indicators of favorable prognosis. CONCLUSIONS: Hormone receptors add to the prognostic information provided by anatomic stage, but the contribution is insufficient to support a decision for or against systemic adjuvant therapy. PMID- 1516032 TI - Anti-oncogenes and the development of tumors in the human nervous system. AB - Two distinct mechanisms of tumorigenesis have been identified in humans. One mechanism is associated with the activation of growth-promoting factors such as proto-oncogenes, growth factors, and growth factor receptors. However, there is overwhelming evidence for the existence of an alternative tumor mechanism that is related to the loss or inactivation of genes that normally suppress cell growth. These genes have been called "anti-oncogenes" or "tumor-suppressor" genes. They appear to be involved fundamentally in the development of many human cancers. This article reviews the potential importance of tumor-suppressor genes in tumor development and growth control in the human nervous system. PMID- 1516033 TI - Gene therapy of cancer through restoration of tumor-suppressor functions? AB - The tools and concepts of gene therapy are being applied to the development of effective new treatments for human cancer. Most human cancers are associated with multiple interacting and cooperating mutations in protooncogenes and tumor suppressor genes. In several model systems, some features of the tumor phenotype can be suppressed in vitro through the restoration of expression of tumor suppressor genes such as Rb and p53. Before this phenomenon can serve as the basis for gene therapy of cancer, many conceptual and technical problems must be solved. Because such genetically modified cells continue to contain and express other mutations, it is important to determine the mechanisms and frequency of reversion to the tumor phenotype. To be clinically useful, highly efficient and targeted gene delivery vectors must be developed. The experimental evidence for tumor suppression by restored gene expression and the pivotal role played by tumor suppressor genes in the regulation of cell replication suggests that restored expression of some tumor suppressor genes in some tumor cells will eventually play a role in cancer gene therapy. PMID- 1516034 TI - Expression of epidermal growth factor receptor and transforming growth factor alpha in human larynx carcinoma. AB - Altered expression of growth factors and growth factor receptors is frequently described in human tumors and human tumor cell lines. This further supports the hypothesis that oncogenesis is due to the subversion of mitogen-responsive pathways. The aim of this study was to investigate the expression of epidermal growth factor receptor (EGFR) and transforming growth factor alpha (TGF alpha) in 13 larynx carcinomas and 2 carcinomas of the oral cavity. We found receptor overexpression in 7 out of 15 tumors at mRNA and/or protein level but low expression in the majority of the normal adjacent tissues. TGF alpha was expressed only in 1 case, but no tyrosine kinase activity of the receptor was detected by antiphosphotyrosine antibody. PMID- 1516035 TI - Inhibitory effects of canthaxanthin on in vitro growth of murine tumor cells. AB - The antitumorigenic effects of carotenoids, in addition to their immuno-enhancing effects, may occur by their direct action on growing tumor cells. To test this hypothesis the direct inhibitory effect of various concentrations of canthaxanthin (CX; 4,4'-diketo-beta-carotene), a non-provitamin A carotenoid, was tested on the in vitro growth of JB/MS, B16F10 melanomas and PYB6 fibrosarcoma and murine non-transformed NIH-3T3 (ATCC CRL 1658) cells. At concentrations of 1 x 10(-8) M up to 1 x 10(-4) M, CX significantly reduced the overall number of tumor cells. The greatest inhibition was observed at a CX concentration of 1 x 10(-4) M after 72 h and 96 h of incubation. However, CX had no inhibitory effect on the growth of the non-transformed NIH-3T3 cell line; rather it significantly enhanced growth of this cell line (P less than 0.05) after 96 h of incubation. Thus, the inhibitory action of CX on growing tumor cells appears to be due to its direct actions on tumor cells and not via its conversion to vitamin A or its immuno-enhancing effects. PMID- 1516036 TI - Chromosome damaging effects of pan masala. AB - Effects of aqueous extracts of a popular brand of pan masala with and without tobacco (PM-T and PM) were studied for short duration treatment employing an in vitro system. Metabolic activation with S9 mix was also included. Frequency of all the three cytogenetic endpoints viz., chromosome aberration (CA); sister chromatid exchange (SCE) and % micronucleated cells (% MNC) were found to be elevated significantly in a dose-dependent manner in cultures without metabolic activation. However, addition of S9 activation system resulted in suppression of chromosomal damage. Our findings indicate that pan masalas contain water soluble direct acting mutagens. PMID- 1516037 TI - Inhibitory effect of diet related sulphydryl compounds on the formation of carcinogenic nitrosamines. AB - N-Nitroso compounds (NOCs) are known to be strong carcinogens in various animals including primates (Preussman and Stewart, (1984) N-Nitroso Compounds). Human exposure to these compounds can be by ingestion or inhalation of preformed NOCs or by endogenous nitrosation from naturally occurring precursors (Bartsch and Montesano, Carcinogenesis, 5 (1984) 1381-1393; Tannebaum (1979) Naturally Occuring Carcinogens, Mutagens and Modulators of Carcinogenesis; Shephard et al., Food Chem. Toxicol., 25 (1987) 91-108). Several factors present in the diet can modify levels of endogenously formed nitrosamines by acting as catalysts or inhibitors. Compounds in the human diet that alter nitrosamine formation would thus play an important role in carcinogenesis study. Earlier researchers have reported the nitrite scavenging nature of sulphydryl compounds (Williams, Chem. Soc. Rev., 15 (1983) 171-196). We therefore studied the modifying effect of sulphydryl compounds viz., cysteine (CE), cystine (CI), glutathione (GU), cysteamine (CEA), cystamine (CEI), cysteic acid (CIA) and thioglycolic acid (TGA) on the nitrosation of model amines viz., pyrrolidine (PYR), piperidine (NPIP) and morpholine (NMOR). Many of these compounds are present in the food we consume. The present work also describes the inhibitory effect of onion and garlic juices on the nitrosation reactions. Both onion and garlic are known to contain sulphur compounds (Block, Sci. Am., 252 (1985) 114-119). Most of these compounds behave as antinitrosating agents and their inhibitory activity towards formation of carcinogenic nitrosamines, under different conditions is described. PMID- 1516038 TI - High prevalence of Inoue-Melnick virus antibodies in patients with colorectal carcinoma. AB - The high prevalence of serum neutralizing antibodies against Inoue-Melnick virus (IMV) among American patients with colorectal carcinoma has been confirmed. Sera from 26 patients with colorectal carcinoma along with the identical number of age and sex-matched patients with non-colorectal neoplasia and normal healthy controls were collected in the Buffalo area. All of the colorectal carcinoma group possessed antibodies against IMV (100%), while antibody positivity for non colorectal neoplasia and for normal controls were 34.6% and 38.5%, respectively. Geometric mean titers of antibodies to IMV type 1 and type 2 for colorectal carcinoma were 266 and 338, respectively, whereas the mean titers in the other two control groups were less than 10.3. These differences between colorectal carcinoma and the two controls were highly significant (P less than 0.001). The majority of patients with colorectal carcinoma had antibodies to both IMV types 1 and 2. PMID- 1516039 TI - Weight loss in a murine cachexia model is not associated with the cytokines tumour necrosis factor-alpha or interleukin-6. AB - Daily administration of an escalating dose of tumour necrosis factor-alpha (TNF alpha) to female NMRI mice caused a progressive loss of body weight representing 12% of the original weight over a 6-day period. Weight loss was associated with a decreased food intake and pair-fed controls exhibited a weight loss of similar magnitude to that caused by TNF-alpha. However, weight loss in animals bearing a murine adenocarcinoma (MAC16) occurred without a change in energy intake and thus differed from that produced by TNF-alpha. Anti-TNF-alpha monoclonal antibodies at levels capable of protecting mice against lethal endotoxaemia were ineffective in reversing weight loss in animals bearing the MAC16 tumour and had no effect on the increase in tumour volume. Circulating levels of interleukin-6 were not elevated in animals bearing the MAC16 tumour and with a weight loss between 1.8 and 5.4 g. These results suggest that these cytokines are not involved in the cachexia produced by this murine tumour. PMID- 1516040 TI - Influence of dietary iron overload on cell proliferation and intestinal tumorigenesis in mice. AB - Iron-enriched diets caused an increase of tumor rate in two models of dimethylhydrazine(DMH)-induced colon tumorigenesis in mice. The effect was independent of the time the iron-diet was fed, i.e. during DMH-treatment or following the DMH-treatment period. The increase of tumor rate depended on the iron concentration in the diet (0.5-3.5%). The concentration-dependent iron accumulation in the colonic mucosa of mice was paralleled by increments of malonaldehyde contents indicating lipid peroxidation, another factor known to be involved in tumor development. It is suggested that iron exerts cocarcinogenic activity in the DMH-model by stimulating cell proliferation and inducing oxidative stress in the colonic mucosa. This effect of iron is independent of the time of tumor-initiation by DMH, as it is also observed in the period of tumor promotion/progression after DMH-treatment. PMID- 1516041 TI - Effects of thiol compounds on methotrexate uptake by murine lymphocytes from thymus and thymic lymphosarcoma. AB - The characteristics of methotrexate (MTX) uptake and the effects of exogenous sulfhydryl compounds (i.e. reduced glutathione and cysteine) on MTX accumulation in thymocytes and thymic lymphosarcoma cells has been studied. Significant differences in the rate and the extent of MTX uptake between normal and neoplastic cells were demonstrated. MTX accumulation was found to be more efficient in thymic lymphosarcoma cells as compared with parental cells. In the cells examined, MTX uptake was not affected by membrane impermeable GSH. In contrast, short-term exposure to cysteine revealed heterogeneity in MTX uptake systems between normal and neoplastic thymocytes. Thus, cysteine was demonstrated to enhance the rate and extent of MTX accumulation exclusively in thymic lymphosarcoma cells. The results obtained indicate that in neoplastic thymocytes biochemical changes had developed in the membrane redox state around the MTX uptake system. These alterations are chemically distinguishable by their characteristic response to cysteine. The findings suggest that the plasma membrane changes could be exploited for preferential enhancement of MTX uptake by neoplastic thymocytes. PMID- 1516042 TI - Local cytokine availability elicits tumor rejection and systemic immunity through granulocyte-T-lymphocyte cross-talk. PMID- 1516043 TI - Newt squamous carcinoma proves phylogenetic conservation of tumors as caricatures of tissue renewal. AB - Although regeneration-competent newts like Notophthalmus viridescens have been reported to be resistant to carcinogenesis, we have been able to induce transplantable epidermal squamous cell carcinomas with 10-20% incidence by implanting 20-methylcholanthrene s.c. into the scapular region, a tissue that cannot regenerate. As soon as 1 week after exposure to this carcinogen, malignant cells were present in the treated skin, and after 4 weeks, macroscopic tumors of infiltrating squamous carcinoma cells positive for Type IV collagenase and/or rasHa p21 had dissolved areas of the epidermal basement membrane and colonized the dermis. Analysis of Ki-67 expression revealed that these tumors grow via a high growth fraction rather than a short cell cycle time. Morphological and immunohistochemical analyses showed that these tumors caricature the biology of the renewing epidermis: the presence of basal-like cells; differentiating cells; apoptotic cells; and keratinized horn pearls with an exaggerated or overabundant stem cell compartment as compared to the differentiated cell compartment. Immunochemical analyses indicated that the squamous carcinomas arose from the epidermis rather than the mucous glands. Thus, the principle that malignant tumors caricature the process of tissue renewal originally established in rodent tumors appears to be valid down the phylogenetic tree at least to regeneration competent amphibia. Such a broad conservation indicates that the caricature principle also holds in human tumors. PMID- 1516044 TI - 4-Hydroxynonenal, a product of cellular lipid peroxidation, which modulates c-myc and globin gene expression in K562 erythroleukemic cells. AB - Several studies point to the existence of an inverse correlation between cellular lipid peroxidation and both cell proliferation and neoplastic transformation. Here, we show that 4-hydroxynonenal (HNE) concentrations close to the level found in normal cells (in the range of 1 and 3 microM) can specifically induce changes in the expression of c-myc and gamma-globin mRNA in K562 cells, without inducing any toxic effects or affecting cell viability. Since we have determined that K562 cells have undetectable levels of endogenous lipid peroxidation, all these effects can be assigned to the exogenous HNE treatment. After a 1-h treatment with 1 microM HNE, c-myc mRNA levels decrease transiently during the first 4 h, rebounding later to higher levels, and normalizing to basal expression after 4 days. Run-on experiments show a transient transcriptional block 20 min after HNE treatment and subsequent posttranscriptional regulation. According to S1 mapping, mRNA changes are exerted on c-myc transcripts initiated from both the principal constitutive start sites (P1 and P2). gamma-Globin mRNA levels concomitantly increase 3- to 4-fold, but no significant changes of housekeeping gene expression are observed. On the basis of these results it appears that the restoration in human erythroleukemic K562 cells of HNE concentrations closer to the level in normal cells can modulate the expression of specific genes. PMID- 1516045 TI - Urinary mutagenicity and N-acetylation phenotype in textile industry workers exposed to arylamines. AB - Primary aromatic amines have been identified epidemiologically as human carcinogens. It has been suggested that the target organ affected by aromatic amines is dependent on the rate of metabolic activation. Epidemiological studies have shown an association between low acetyl transferase activity and bladder cancer risk. On this basis, our working hypothesis was that the slow acetylators could follow in a higher extent the metabolic pathway independent of N acetylation, leading to the excretion of conjugates of electrophyles with glucuronic acid. The instability of these glucuronides could be responsible for the association between arylamine-induced bladder cancer and slow acetylator phenotype. A total of 153 individuals were included in this study: 70 exposed to arylamines (working in textile industry) and 83 nonexposed. The following parameters were determined in urine: mutagenic index in the absence of metabolic activation, S9; mutagenic index in the presence of S9; and the mutagenic index after incubation of the urine with beta-glucuronidase. All individuals were phenotyped according to their capacity of N-acetylation by using isoniazid as drug test. The results show that the mutagenic index after incubation of the urine with beta-glucuronidase is statistically higher in exposed subjects when compared with nonexposed individuals (P less than 0.001), this parameter being statistically higher among exposed subjects who were slow acetylators than among rapid metabolizers, independent of the fact that they were smokers or nonsmokers. There were no significant differences between groups for the mutagenicity in urine not incubated with beta-glucuronidase. PMID- 1516046 TI - Metabolic effects and kill of human T-cell leukemia by 5 deazaacyclotetrahydrofolate, a specific inhibitor of glycineamide ribonucleotide transformylase. AB - Metabolic effects and mode of cytotoxicity of 5-deazaacyclotetrahydrofolate (5 DACTHF, BW543U76), a glycineamide ribonucleotide transformylase inhibitor, were studied in MOLT-4 cells, a human T-cell leukemia line. 5-DACTHF inhibits purine synthesis with 50% inhibitory concentration values of 0.5 microM and 0.08 microM following 6- or 24-h exposure to drug, respectively. At 6 h, adenine nucleotide synthesis is preferentially inhibited over guanine nucleotide synthesis. A similar effect was observed with another glycineamide ribonucleotide transformylase inhibitor, 5,10-dideazatetrahydrofolate. GTP was depleted to 40% of control and ATP to 10% of control by 5 microM 5-DACTHF. After a transitory increase, UTP and CTP were depleted to 30% of control. Deoxynucleotides were also depleted by the drug; dCTP was depleted to the greatest extent, followed by dATP, dTTP, and dGTP, respectively. MOLT-4 cell growth was inhibited by 5-DACTHF with a 50% inhibitory concentration of 0.066 microM. Complete reversal was effected by hypoxanthine, and there was no reversal by thymidine. The drug was cytotoxic to MOLT-4 cells in the range 0.25 to 5.0 microM, but a minimum of 48 h was required for trypan blue-staining dead cells to appear. The rate and extent of kill with the thymidylate synthase inhibitor 2-methyl-10-propargyl-5,8-dideazafolate was greater than with 5-DACTHF, which indicates that kill by inhibition of thymidylate synthase is more effective than that by inhibition of purine synthesis. Electron microscopy of MOLT-4 cells exposed to 5-DACTHF showed electron-dense mitochondria and nuclear changes reminiscent of apoptosis. These morphological changes were accompanied by the appearance of DNA strand breaks at approximately 180-base pair intervals (internucleosomal breaks). Concomitant proteolysis of nuclear proteins poly(ADP-ribose) polymerase and lamin B was observed. PMID- 1516047 TI - Cytotoxicity and antitumor activity of carzelesin, a prodrug cyclopropylpyrroloindole analogue. AB - The cyclopropylpyrroloindole analogues are DNA minor-groove binders containing a cyclopropyl group, which mediates N3-adenine covalent adduct formation in a sequence-selective fashion. Carzelesin (U-80244) is a cyclopropylpyrroloindole prodrug containing a relatively nonreactive chloromethyl precursor to the cyclopropyl function. Activation of carzelesin requires two steps, (a) hydrolysis of a phenylurethane substituent to form U-76073, followed by (b) ring closure to form the cyclopropyl-containing DNA-reactive U-76074. The formation of the DNA reactive U-76074, via U-76073, from carzelesin was shown to proceed very slowly in phosphate-buffered saline (t1/2 greater than 24 h) but to occur rapidly in plasma from mouse, rat, dog, and human (initial t1/2 values ranging from 18 min for mouse to 52 min for rat) and in cell culture medium (t1/2 approximately 40 min). Although carzelesin was less potent in terms of in vitro cytotoxicity and in vivo optimal dosage and showed low affinity for binding to DNA, it was therapeutically more efficacious against mouse L1210 leukemia than was U-76074 or adozelesin (U-73975), another cyclopropylpyrroloindole analogue which is currently in phase I clinical trials. Carzelesin also proved to be more efficacious than U-76074 or adozelesin against mouse pancreatic ductal 02 adenocarcinoma, a system reported to be resistant to every agent tested. Carzelesin was highly effective against this tumor and produced 97% tumor growth inhibition. In addition, i.v. administered carzelesin showed significant activity (National Cancer Institute criteria) against i.v. or s.c. implanted Lewis lung carcinoma, i.p. or s.c. implanted B16 melanoma, s.c. implanted colon 38 carcinoma, and five s.c. implanted human tumor xenografts, including clear cell Caki-1 carcinoma, colon CX-1 adenocarcinoma, lung LX-1 tumor, ovarian 2780 carcinoma, and prostatic DU-145 carcinoma. Carzelesin treatment produced 100% complete remissions (no palpable tumor mass at the termination of the experiment) in mice bearing early-stage human ovarian 2780. Pharmacologically, carzelesin proved to be relatively schedule and route independent and was highly active against i.p. implanted L1210 leukemia, regardless of whether the analogue was given i.v., i.p., s.c., or p.o. These results, collectively, suggest that carzelesin is absorbed and distributed well. Both carzelesin and adozelesin caused marked tumor shrinkage in mice bearing human lung LX-1 or advanced-stage human ovarian 2780 carcinoma; however, tumor regrowth occurred shortly after the treatment with adozelesin was stopped. Little or no apparent tumor regrowth occurred after treatment with carzelesin.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1516048 TI - Elevation of thymidylate synthase following 5-fluorouracil treatment is prevented by the addition of leucovorin in murine colon tumors. AB - The inhibition of thymidylate synthase (TS) by the 5-fluorouracil (5FU) metabolite 5-fluorodeoxyuridine monophosphate can be biochemically modulated by leucovorin (LV). LV administration increases the level of reduced folates in tissues, which promotes the inhibition of TS. We have studied the antitumor effect, free 5-fluorodeoxyuridine monophosphate levels, and inhibition of TS in two murine colon tumors at several time points after weekly 5FU or LV and 5FU administration. The antitumor effect of 5FU alone could be potentiated by LV in both tumors. 5-Fluorodeoxyuridine monophosphate levels (212 and 46 pmol/g wet wt. after 2 h for Colon 26 and Colon 38, respectively) were sufficient to mediate TS inhibition, but the levels were not related to antitumor activity. Untreated controls of the 5FU-sensitive tumor Colon 38 had 3 times lower TS levels than did those of the more resistant tumor Colon 26. One course of treatment resulted in a comparable extent and retention of TS inhibition for 5FU and LV/5FU therapy in both tumors. After 1 week there was complete recovery of TS inhibition, but the TS levels in tumors from 5FU-treated mice tended to be higher than the controls, which was more pronounced after three courses of therapy. A 4-fold increase of TS levels was seen in Colon 26 after 5FU therapy. The elevation of TS in this tumor affected the extent of TS inhibition. Tumors treated with 5FU and LV also showed an increase of TS, but to a lesser extent, while the absolute effect on TS inhibition remained the same. This might be related to the potentiating effect of LV on 5FU antitumor activity in vivo in these tumors. PMID- 1516049 TI - Structural chromosome 1 aberrations in transitional cell carcinoma of the bladder: interphase cytogenetics combining a centromeric, telomeric, and library DNA probe. AB - Fluorescence in situ hybridization (FISH) was used to study numerical and structural chromosome 1 aberrations in interphase nuclei of transitional cell carcinomas (TCCs) of the urinary bladder. One of the characteristic numerical aberrations, as detected previously in low-grade noninvasive TCCs, included trisomy for chromosome 1 (A. H. N. Hopman et al., Cancer Res., 51: 644-651, 1991). We examined in more detail 22 cases with a centromeric (1q12) and a telomeric associated (1p36) DNA probe and with a library DNA probe from sorted human chromosome 1 in single- and double-target FISH procedures. All flow cytometrically determined DNA diploid TCCs (13 cases), which showed three spots for 1q12 (6 cases), had two spots for 1p36. Since the library DNA probe showed three separate domains in the nuclei of these cases, the additional copy for 1q12 could be explained as an extra chromosome 1p-, containing the 1q12 target. In the flow cytometrically determined DNA tetraploid/aneuploid tumors, the results were more complex. In 6 of 9 cases, we observed an overrepresentation of 1q12 as compared to 1p36, also suggesting the presence of extra copies of 1p- chromosomes. The results of the present study demonstrate the utility of the FISH method to assess structural chromosome aberrations in interphase nuclei of solid tumors. PMID- 1516050 TI - Low mitochondrial proton leak due to high membrane cholesterol content and cytosolic creatine kinase as two features of the deviant bioenergetics of Ehrlich and AS30-D tumor cells. AB - Isolated mitochondria from highly glycolytic Ehrlich and AS30-D tumor cells have a 12.4- and a 2.3-fold higher cholesterol level, respectively, than that of rat liver mitochondria. The passive proton permeability of Ehrlich and AS30-D tumor inner membrane mitochondria is, respectively, 4- and 1.4-fold lower than that of rat liver mitochondrial membrane. This feature is accompanied by a lower proton leak current in tumor mitochondria. A 3.5-fold cholesterol enrichment of rat liver mitochondria decreases their passive proton permeability by a factor of 2, thus establishing a direct relationship between the cholesterol contents of mitochondrial membranes and the passive proton permeability. Creatine kinase activity is present in the cytosol of these cells and is mostly represented by the BB isoform. Since AS30-D tumor cells' treatment with the creatine analogue beta-guanidinopropionic acid decreases their life span and viability, creatinine kinase is an indispensable enzyme entering a main energy distribution pathway starting from mitochondrial ATP, through glycolysis and creatine phosphorylation, to satisfy the large energy demands of tumor cell division. PMID- 1516051 TI - Cell surface accessibility of individual gangliosides in malignant melanoma cells to antibodies is influenced by the total ganglioside composition of the cells. AB - The reactivity of a panel of antiganglioside monoclonal antibodies with a number of melanoma cell lines having different ganglioside composition profiles was studied. One cell line synthesized only GM3, one produced both GM3 and GD2, 2 had GM3 and GD3 as their major gangliosides, and 2 others synthesized approximately equal amounts of GM3, GM2, GD3, and GD2 gangliosides. Antibody reactivity with viable cells was analyzed by: (a) flow cytometry on suspension cells; and (b) mixed hemagglutination assays or immune adherence assays on monolayer cells in culture. GM3 was efficiently detected only in the cell line having GM3 as its sole ganglioside. In the other cell lines, GM3 was difficult to detect even in cells in which it made up a high proportion (up to 50%) of the total ganglioside content. GM2 was easily detectable only in JB-RH melanoma cells (which contain only GM3 and GM2). GD3 was the most reactive ganglioside in 2 cell lines and GD2 in 2 other lines. In general, the most complex ganglioside present in a cell was the one most accessible to antibody. The differential exposure at the cell surface of specific gangliosides may have implications for antibody-directed tumor detection and therapy and for cell-protein or cell-cell interactions that involve glycolipids. PMID- 1516052 TI - Effects of hyperthermia on blood flow and cis-diamminedichloroplatinum(II) pharmacokinetics in murine mammary adenocarcinomas. AB - The effect of localized hyperthermia on blood flow and cis diamminedichloroplatinum(II) (CDDP) pharmacokinetics in 7,12 dimethylbenz[a]anthracene-induced mammary adenocarcinomas was studied. Blood flow was determined in rat tumors and normal tissue immediately and 1, 2, and 3 h after local hyperthermia treatment (43 degrees C, 1 h) as well as in unheated tumors of rats. The rate of blood flow in the tumor was increased 1.9 times at the end of treatment relative to control values and returned to the control values by 3 h after hyperthermia. Similarly, the rate of blood flow in the peripheral skin around the tumor immediately after hyperthermia was 2.2 times greater than that of unheated skin and returned to near normal values by 3 h after heating. Tumor-bearing rats received CDDP 1 h before, at the beginning of, at the end of, and 1 h after hyperthermia administration. The CDDP plasma concentration versus time profiles for rats did not vary statistically between treatment groups. Two h after CDDP administration, the mean tumor CDDP concentration of the rats which received drug at the beginning of hyperthermia was statistically greater (P less than 0.05) than tumor CDDP concentrations in rats which received drug at the end of heat treatment. The latter group was given CDDP when tumor blood flow was the greatest; however, mean tumor drug concentration was lowest of all the groups. The mean drug concentration in tumor tissues of rats which received drug 1 h after hyperthermia was comparable to rats which received drug at the beginning of hyperthermia. This suggests that drug delivery or uptake in tumors may be altered when local hyperthermia is administered concurrently or sequentially. PMID- 1516053 TI - Tamoxifen suppresses tumor promoter-induced hydrogen peroxide formation by human neutrophils. AB - Trans-tamoxifen (TAM) has been used successfully in therapy for estrogen dependent human breast tumors and prevention of their recurrence. The mechanism of this prevention was thought to be due to the interference of TAM with estrogen promotion. TAM has a wider anticarcinogenic action that is similar to other chemopreventive agents in that it suppresses tumor promotion in 2-stage carcinogenesis by interfering with the action of protein kinase C. We report that TAM (5 microM) totally inhibits hydrogen peroxide (H2O2) formation by 12-O tetradecanoyl-phorbol-13-acetate (TPA)-treated human neutrophils. Interestingly, beta-estradiol (10 microM) also slightly inhibits the oxidative burst of neutrophils. Pretreatment of neutrophils with varying amounts of TAM and beta estradiol caused additive inhibition of H2O2 formation by the 2 agents. 4-Hydroxy tamoxifen, a metabolite with the highest affinity for the estrogen receptor, was only as inhibitory as beta-estradiol. Other derivatives (cis-, N-desmethyl-, and N-desdimethyl-tamoxifen) with low biological activities had a smaller effect on H2O2 formation. TPA-treated neutrophils were shown to contain 5-hydroxymethyl uracil (HMU). TAM prevented the TPA-induced formation of HMU in other cells. Like TPA, dietary fat, which is a risk factor for breast cancer, induces formation of HMU in the DNA of human white blood cells. TAM may suppress the dietary fat induced HMU in the same manner at it does in TPA-induced neutrophils. PMID- 1516054 TI - Chemoprevention of rat liver carcinogenesis by S-adenosyl-L-methionine: a long term study. AB - Previous work has shown a consistent fall in S-adenosyl-L-methionine (SAM) in the liver of diethylnitrosamine-initiated rats, during the development of preneoplastic lesions, in persistent nodules (PNs), and hepatocellular carcinomas. The injection of SAM into rats causes the reconstitution of the SAM pool, coupled with growth restraint, remodeling, and apoptosis of preneoplastic cells, and inhibits the development of PNs and hepatocellular carcinomas. To evaluate if SAM treatment causes a long-term prevention of preneoplastic and neoplastic liver lesions or merely causes a delay in their development, we evaluated the effect of a relatively short SAM treatment on the development of preneoplastic and neoplastic lesions in a long-term study. Male Wistar rats were subjected to initiation with diethylnitrosamine, followed by selection and then by the administration of phenobarbital for 16 weeks. After selection, the rats were given i.m. injections of a purified SAM preparation (384 mumol/kg/day) for 24 weeks. In SAM-treated rats, a decrease in the incidence of PNs was found 6, 14, and 24-28 months after initiation. At the end of SAM treatment the number of PNs per rat liver, nodule diameter, and labeling and mitotic indices of nodular cells decreased considerably in control rats. Nodule diameter started to increase rapidly again only 8 months after arresting SAM treatment, when complete recovery of DNA synthesis in nodular cells occurred. The majority of nodules present in the liver 6-28 months after initiation belonged to the clear and acidophilic cell types, with lower percentages of mixed cell and basophilic cell types. A decrease in basophilic nodules occurred in SAM-treated rats. Fourteen and 24-28 months after initiation hepatocellular carcinoma incidence was 11 of 12 and 10 of 10 in control rats, respectively, and only 1 of 12 and 3 of 11 in SAM-treated rats. At the 24th-28th month all control rats had tumors identified as 2 poorly differentiated carcinomas, 6 trabecular carcinomas, or 3 adenocarcinomas, while only 2 relatively small trabecular carcinomas and 1 small glandular tumor developed in SAM-treated rats. In 3 of 11 SAM-treated rats, but in none of the control rats, leukemic infiltration of liver occurred 24-28 months after initiation. Leukemic infiltration of the spleen occurred in 5 and 3 control and SAM-treated rats, respectively.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1516055 TI - Folate deficiency enhances the development of colonic neoplasia in dimethylhydrazine-treated rats. AB - In patients with ulcerative colitis, epidemiological work has suggested an association between low folate status and an increased risk of colonic neoplasia. The aim of the present study was to determine if experimental folate deficiency increases the likelihood of developing neoplasia in rats treated with the carcinogen dimethylhydrazine. Weanling male Sprague-Dawley rats were fed with an amino acid-defined diet containing either 8 or 0 mg/kg folic acid. After 5 weeks of defined diet, weekly s.c. injections of dimethylhydrazine (20 mg/kg) were administered to both groups. Serum, whole blood, liver, and colonic folate concentrations at the time of sacrifice were significantly lower in folate depleted animals (P less than 0.001). There were significant differences in the incidence of colonic neoplasia between the two groups after 20 weeks of dimethylhydrazine exposure: folate-deficient rats had a greater incidence of dysplasia (6 of 7 versus 2 of 7 animals; P less than 0.05) and carcinoma (6 of 7 versus 1 of 7 animals; P less than 0.01). Furthermore, a significantly greater proportion of folate-replete rats than folate-deficient rats were free of neoplastic lesions (5 of 7 versus 0 of 7 animals; P less than 0.05). These results suggest that, in this animal model, folate deficiency increases the risk of malignancy when there is an underlying predisposition to colorectal cancer. PMID- 1516056 TI - Differential chromatin structure-dependent binding of 7-aminoactinomycin D in normal and malignant bone marrow hematopoietic cells. AB - Chromatin structure-dependent binding of the DNA-specific dye 7-aminoactinomycin D (7-AMD) in leukemic and normal cells in bone marrow aspirates from childhood acute leukemia patients and patients without bone marrow neoplasia was assessed by multiparameter flow cytometry. Simultaneous staining with fluorescein isothiocyanate-labeled antibodies was needed in many cases for determination of the immunophenotype of the cells that exhibited differential binding of 7-AMD. 7 AMD binding was enhanced in normal (4 patients) and malignant (8 patients) myeloid cells, and was generally low in normal and leukemic lymphocytes and normoblasts. Four of 18 aspirates from 16 patients with acute lymphoblastic leukemia contained neoplastic cells with increased 7-AMD binding capability. The 7-AMD binding of the leukemic cells was not correlated to S-phase fraction (P = 0.07), but was significantly correlated to cell size as measured by forward angle light scattering (r = 0.49, P = 0.007). Patients with tumor cells exhibiting low 7-AMD binding at last aspirate survived significantly longer than the patients with leukemic cells binding high amounts of 7-AMD (P = 0.03). Neither cell size, S-phase fraction, nor ploidy status predicted patient survival in this small scale study. PMID- 1516057 TI - Differences in basic fibroblast growth factor RNA and protein levels in human primary melanocytes and metastatic melanoma cells. AB - Cultivation of human melanocytes requires several growth factors for cell proliferation. For example, basic fibroblast growth factor (bFGF) is an essential growth agent for melanocyte proliferation in vitro and has been proposed to be an autocrine growth factor in human melanoma cells. Studies using either anti-bFGF antibodies or antisense oligonucleotides partially inhibited the proliferation of human melanoma cells. However, one group was unable to detect bFGF RNA transcripts in human melanoma cells using a human complementary DNA probe. These contradictory results prompted us to investigate the bFGF gene expression in human primary melanocytes and metastatic melanoma cells using Southern, Northern, and Western blot analyses. No gross rearrangements in the bFGF gene were detected in the genomic DNA. Although high levels of bFGF RNA transcripts were detected in melanocytes, no bFGF protein was detected using Western blot analysis. In contrast, melanoma cells expressed much lower levels of bFGF RNA transcripts, and cells from three of four cell strains synthesized the multiple isoforms of bFGF protein. In one of the melanoma cell strains, no bFGF protein was detected using Western blot analysis. Although three of four melanoma cell strains expressed bFGF protein, this molecule does not appear to function as an autocrine growth factor, and expression of the bFGF protein was not a consistent alteration in all melanoma cell strains. PMID- 1516059 TI - Mammary tumor induction by N-methyl-N-nitrosourea in genetically resistant Copenhagen rats. AB - The Copenhagen rat is completely resistant to mammary cancer induction by N methyl-N-nitrosourea (MNU) when the carcinogen is administered during sexual development, a period when other strains of rats are normally susceptible to mammary gland carcinogenesis. Here we administered 30 mg/kg MNU i.p. to two groups of neonatal (2-3-day-old) Copenhagen rats. One group (group B, 18 animals) received no further treatment, while the other group (group C, 17 animals) received a second dose of 30 mg/kg MNU via the tail vein at 50 days of age. About 30% of the rats in group B and about 70% of those in group C developed mammary carcinomas before they were 1 year of age. About one-half of the tumors in both groups were cribriform adenocarcinomas and one-half were adenosquamous carcinomas. The latter tumor type has not been observed previously in susceptible rat strains. The ability to induce these mammary tumors in the Copenhagen rat suggests that the putative mammary carcinoma suppressor gene is functionally inactive in neonatal animals or is inactivated when these animals are treated with MNU. PMID- 1516058 TI - Human urinary bladder carcinoma glycoconjugates expressing T-(Gal beta(1-3)GalNAc alpha 1-O-R) and T-like antigens: a comparative study using peanut agglutinin and poly- and monoclonal antibodies. AB - T- and T-like antigens on glycoproteins and glycolipids were examined in extracts of human urinary bladder tumors and normal tissue by Western blot analysis and reagent binding to thin layer chromatograms. Three different anti-T-reagents were used: peanut (Arachis hypogaea) lectin (PNA) and mono- and polyclonal antibodies specific for T-antigen (Gal beta(1-3)GalNAc alpha 1-O-R). Immunodetection with the T-specific reagents in nitrocellulose replicas of bladder tumor glycoproteins, separated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis, demonstrated tumor-specific T-antigen-bearing glycoproteins compared to normal urothelial glycoproteins. In addition, a remarkable difference in binding was found between the immunological reagents and PNA lectin. PNA showed major reactivity to a 28-kD glycoprotein extracted from tumors. Monoclonal anti-T-antibody (clone HH8) showed major reactivity with an M(r) 34,000 glycoprotein, and polyclonal anti-T-antibody showed major reactivity with an M(r) 36,000 glycoprotein. PNA agarose column affinity-purified tumor glycoproteins did not bind the antibodies. Glycoproteins, M(r) 28,000 and 34,000, were shown to be O-linked by stepwise deglycosylation. In solid phase monosaccharide inhibition tests, galactose followed by N-acetyl-galactosamine were the most potent monosaccharides inhibiting binding to immobilized bladder tumor glycoproteins. None of the anti-T-reagents reacted with glycolipids extracted from tumor tissue. It is concluded that PNA lectin, in addition to the T-disaccharide, reacts with other protein-anchored carbohydrate structures in carcinomas. PMID- 1516060 TI - High incidence of hepatocellular carcinomas induced by a choline deficient L amino acid defined diet in rats. AB - The carcinogenicities of a choline deficient L-amino acid defined (CDAA) diet and a semipurified choline deficient diet were comparatively examined. A total of 60 male Fischer 344 rats, 6 weeks old, were divided into 5 experimental groups each consisting of 12 rats. Group 1 received the CDAA diet chronically to the end of the 52-week experiment while Group 2 was given the same diet for the first 24 weeks and then a basal diet for the following 28 weeks. Groups 3, 4, and 5 received a choline supplemented L-amino acid defined diet, the semipurified choline deficient diet, and a semipurified choline supplemented diet, respectively, throughout the experimental period. All surviving rats were subjected to complete macroscopic examination at Week 52. Histopathologically diagnosed hepatocellular carcinomas were induced in Group 1 at an incidence of 100%; multiple metastatic nodules were seen in the lungs of one of the animals. Hepatocellular carcinomas were also induced in Group 4 rats at a significantly lower incidence of 20%. No hepatocellular carcinomas were observed in rats in Groups 2, 3, and 4. The results indicate that the CDAA diet exerts more potent carcinogenicity for the livers of rats than does the semipurified choline deficient diet. However, limited exposure for 24 weeks may have not been sufficient for hepatocellular carcinoma induction by the CDAA diet at Week 52 although a high incidence of hyperplastic nodules and slight cirrhosis were evidence of persistent lesions. PMID- 1516061 TI - Localization of fluorine-18-labeled Mel-14 monoclonal antibody F(ab')2 fragment in a subcutaneous xenograft model. AB - Positron emission tomography is an imaging method that might improve the effectiveness of radioimmunoscintigraphy and might provide more accurate estimates of monoclonal antibody dosimetry prior to therapy. Because of its widespread availability, 2-h half-life 18F could be a useful nuclide for labeling monoclonal antibody fragments, provided that adequate tumor uptake and satisfactory tumor:normal tissue ratios could be achieved rapidly. In this study, the tissue distribution of 18F-labeled Mel-14 F(ab')2, a monoclonal antibody reactive with gliomas, was evaluated in a s.c. athymic mouse human glioma xenograft model. 18F labeling was performed using N-succinimidyl-8-(4 [18F]fluorobenzylamino) suberate. For paired-label comparisons both in vitro and in vivo, Mel-14 F(ab')2 was also labeled using N-succinimidyl 3- [125I]- iodobenzoate. When 100-120 micrograms of disuccinimidyl suberate was used in the 18F-labeled acylation agent synthesis, the binding of 18F-labeled Mel-14 F(ab')2 to glioma homogenates was comparable to that of the radioiodinated fragment. Scatchard analyses indicated nearly identical affinity constants for fragments with both labels (18F, 6.4 x 10(8) M-1; 125I, 6.7 x 10(8) M-1). Tumor levels of 18F increased between 1 and 2 h and then were relatively constant between 2 and 6 h. When lower levels of disuccinimidyl suberate were used, there was an excellent correlation between 18F and 125I tumor uptake (r = 0.984, slope 1.03-1.04). At 4 h, tumor:normal tissue ratios for 18F-labeled Mel-14 F(ab')2 in liver, spleen, muscle, and brain were 2.3, 4.2, 14, and 40, respectively. Localization indices, determined by comparison with 18F-labeled nonspecific F(ab')2, were 3.7 at 4 h and 6.9 at 6 h for tumor and about 1 for normal tissues, indicating the specificity of 18F-labeled Mel-14 F(ab')2 tumor uptake. PMID- 1516062 TI - Role of p53 mutations in endocrine tumorigenesis: mutation detection by polymerase chain reaction-single strand conformation polymorphism. AB - To elucidate the molecular basis for endocrine tumorigenesis, p53 mutations in human endocrine tumors were analyzed by using polymerase chain reaction-single strand conformation polymorphism. Exons 5 through 10 of the p53 gene were studied in genomic DNAs from 134 primary endocrine tumors and 6 human endocrine cancer derived cell lines. Mutations were detected and identified in 4 endocrine tumors, including one parathyroid adenoma and three thyroid carcinoma cell lines. The sites of these mutations were in exons 5 (codon 151 and 152) and 7 (codon 248 and 255). In all of three tumor cell lines, but not in a parathyroid adenoma, the normal allele encoding the p53 gene was lost. However, p53 mutations were not found in any other endocrine tumors or cell lines. Based upon these results, we concluded that the p53 gene may play a role in the tumorigenesis of a limited number of parathyroid adenoma and thyroid cancers, and that the p53 mutation with an allelic loss of the p53 gene is an important factor in malignant tumorigenesis of the thyroid gland. PMID- 1516063 TI - Activation of the trans geometry in platinum antitumor complexes: a survey of the cytotoxicity of trans complexes containing planar ligands in murine L1210 and human tumor panels and studies on their mechanism of action. AB - The cytotoxicity of transplatinum complexes of structural formula trans [PtCl2(L)(L')] [L = L' = pyridine or thiazole, or L = quinoline (R' = methyl; R" = methyl, phenyl, or CH2phenyl) and L' = R'R"SO] has been studied in murine L1210 and human tumor cell lines. The results confirm previous observations that use of a sterically hindered planar ligand greatly enhances cytotoxicity, in comparison to trans-[PtCl2(NH3)2], such that in some cases cytotoxicity equivalent to that of the clinically used agent cisplatin [cis-[PtCl2(NH3)2]] is obtained. Results from both the panel of human ovarian carcinoma cell lines and the National Cancer Institute screening panel confirm a different pattern of cytotoxicity, with respect to cisplatin. The new trans-platinum complexes are also non-cross resistant with cisplatin in both murine and human (human ovarian carcinoma panel) tumor cell lines. Preliminary mechanistic studies using both cis- and trans [PtCl2(pyridine)2] in L1210 cells have been carried out, to delineate the reasons for both the dramatically enhanced cytotoxicity and the lack of cross-resistance with the clinically used agents. Intracellular uptake is enhanced for pyridine relative to ammine (NH3) complexes. The pyridine complexes also inhibit DNA synthesis, implying a role for DNA binding in their mechanism of action. Binding of the pyridine complexes to calf thymus DNA is, however, significantly less than for the analogous ammine complexes. The presence of trans-pyridine ligands results in steric hindrance, which retards the rate of reaction of trans [PtCl2(pyridine)2], relative to trans[PtCl2(NH3)2], with other important biomolecules such as glutathione. The results point to a potential new class of platinum antitumor complexes acting by a new mechanism and with activity complementary to agents such as cisplatin. PMID- 1516064 TI - Cellular kinetics of rat mammary gland terminal end bud epithelium exposed to N methyl-N-nitrosourea in vivo. AB - Administration of the direct acting carcinogen N-methyl-N-nitrosourea (NMU) to 50 55-day-old virgin female rats on different days of the estrous cycle yields differential breast tumor biology (T. A. Ratko and C. W. Beattie, Cancer Res., 45: 3042-3047). One basis for these estrous cycle-dependent differences may be the duration of cell cycle stages of susceptible structures such as mammary terminal end buds or the quantity and duration of repair effected following adduct formation within these structures. The terminal end bud (TEB) epithelial cell cycle was characterized using pulse injections of [3H]thymidine (0.5 mCi/g body weight). On estrus, TEB epithelial cell cycle was significantly shorter (15.5 h) than on proestrus (19.9 h) and diestrus (18.8 h). The shorter duration in TEB cell cycle on estrus was likely due to a shorter TG1 (3-4 h) (P less than 0.05) since TS and TG2 did not differ between estrous cycle days. When NMU was injected 1 h after [3H]thymidine, the labeled mitotic wave within TEB of diestrus rats recovered approximately 2-3 h sooner than those given injections during proestrus (P less than 0.01), suggesting less initial damage or a slightly faster rate of DNA adduct repair. When [3H]thymidine was injected 1-5 days after the NMU, the percentage of labeled mitoses of rats given injections during diestrus and proestrus recovered to near normal 48 h after NMU, although the proportion of all cells labeled was still low compared to non-NMU-treated rats. The percentage of labeled mitoses and labeling of cells were normal 3 and 5 days after NMU. Rats receiving a carcinogenic but sublethal dose of NMU (5 mg/100 g body weight), followed by [3H]thymidine injection within 1 min, had one-half the intensity of thymidine incorporation into the terminal end bud DNA of non-NMU-treated rats. Unscheduled DNA synthesis was not demonstrable within the first 48 h following injection of NMU. The results support and extend the finding that rat mammary epithelial cell carcinogenicity of NMU is estrous cycle dependent and appears to be correlated with a differential response in the cell cycle of TEB (shorter at estrus) or delayed recovery in response to NMU (proestrus versus diestrus). PMID- 1516065 TI - Ectopic expression of epidermal growth factor receptors induces hormone independence in ZR-75-1 human breast cancer cells. AB - Epidermal growth factor (EGF) receptor is inversely related to expression of estrogen receptor (ER) and progesterone receptor in primary breast tumors and is a negative predictor for response to endocrine therapy. To investigate a possible causal role of EGF receptor expression in breast cancer progression to hormone independence, we have created an experimental cell system. Epidermal growth factor receptor complementary DNA was introduced in estrogen-dependent ZR-75-1 breast cancer cells, and the resulting ZR/HERc cells exhibited a mitogenic response to epidermal growth factor, thus bypassing estrogen dependence. This EGF induced proliferation could not be inhibited by antiestrogens. In addition, we noted changes in cell morphology and keratin expression of EGF-stimulated ZR/HERc cells, suggestive of an altered differentiation state. Furthermore, intolerance of functional ER and EGF receptor signal transduction pathways in ZR/HERc cells was observed during simultaneous activation, which possibly explains the inverse relationship of ER and EGF receptor expression in primary tumors. In contrast to the parental cells, ZR/HERc cells rapidly progressed to a stable ER-negative phenotype when cultured in the presence of the antiestrogen hydroxy-tamoxifen. These results suggest a possible role for EGF receptor in progression of breast cancer to hormone independence. PMID- 1516066 TI - Cytotoxicity of Clostridium difficile toxin A for human colonic and pancreatic carcinoma cell lines. AB - The use of bacterial exotoxins may constitute novel adjuncts to treatment of gastrointestinal tract malignancies. Clostridium difficile toxin A was evaluated for its cytotoxic effect in vitro on 24 human cell lines and strains including carcinomas of the colon, pancreas, prostate, lung, breast, and lymphoid malignancies, as well as nonmalignant tissues. All nine colon and five pancreas cell lines were extraordinarily sensitive to the cytotoxic effect of Clostridium difficile toxin A at very low concentrations. This effect, which occurred rapidly and was dose dependent, was observed in all cells of seven colon and two pancreas cell lines at concentrations as low as 1-5 ng/ml (10(-12) to 10(-11) M), whereas cells derived from other sites required 60 to greater than 500 ng/ml to achieve an equivalent effect. The data suggest that Clostridium difficile toxin A may have potential therapeutic value in the treatment of some gastrointestinal tract cancers. PMID- 1516067 TI - Expression of the cellular adhesion molecule E-cadherin is reduced or absent in high-grade prostate cancer. AB - E-cadherin is a Ca(2+)-dependent cell adhesion molecule which plays an important role in normal growth and development via mediation of homotypic, homophilic cell cell interaction. Recent studies suggest that E-cadherin may be important in neoplastic progression as well, particularly as a suppressor of invasion. We have previously demonstrated that the invasive phenotype of rat prostate cancer cells is associated with the decreased expression of E-cadherin (M. J. G. Bussemakers, R. J. A. Van Moorselaar, L. A. Giroldi, T. Ichikawa, J. T. Isaacs, F. M. J. Debruyne, and J. A. Schalken, Cancer Res., 52:2916-2922, 1992). This is of particular interest, since the locus to which the human E-cadherin gene is mapped is frequently involved in allelic loss in prostate cancer (B. S. Carter, C. M. Ewing, W. S. Ward, B. F. Treiger, T. W. Aalders, J. A. Schalken, J. I. Epstein, and W. B. Isaacs, Proc. Natl. Acad. Sci. USA, 87:8751-8755, 1990; U. S. Bergerheim, K. Kunimi, V. P. Collins, and P. Ekman, Genes, Chromosomes Cancer, 3: 215-220, 1991). Impaired E-cadherin function is likely to be associated with aberrant expression of the protein. We therefore analyzed E-cadherin expression in situ by immunohistochemistry in nonmalignant and malignant specimens of human prostatic tissue. Of 92 tumor samples of either primary or metastatic deposits of prostate cancer, 46 had reduced or absent E-cadherin staining when compared to nomalignant prostate, which uniformly stained strongly positive. There was a statistically significant correlation between the decreased expression of E cadherin and loss of tumor differentiation. Additionally, certain tumors within a histologically similar group could be distinguished by the presence of mixed populations of E-cadherin-negative and -positive cells. The percentage of tumors with aberrant E-cadherin staining increased when clinically localized tumors were compared to either tumors with extensive local progression or metastatic deposits of prostate cancer, suggesting a correlation between loss of E-cadherin and tumor progression. Taken together, these findings suggest that further exploration of E cadherin as a candidate invasion suppressor molecule in human prostate cancer is warranted. PMID- 1516068 TI - Microvascular pressure is the principal driving force for interstitial hypertension in solid tumors: implications for vascular collapse. AB - The interstitial fluid pressure (IFP) has been found to be as high as 20 to 50 mm Hg in both experimental and human solid tumors. While the IFP is an important determinant of the delivery of therapeutic agents to neoplastic cells in vivo, the mechanisms responsible for interstitial hypertension are not completely understood. The high vascular permeability of tumor blood vessels and the absence of a functional lymphatic circulation suggest that the hydrostatic microvascular pressure (MVP) is the main force governing IFP in tumors. To test this hypothesis, we simultaneously measured IFP and MVP in 13 tissue-isolated R3230AC mammary adenocarcinomas transplanted in rats. The MVP in superficial postcapillary venules of diameters between 25 and 250 microns was measured with the micropuncture technique. MVP was compared to the IFP in the periphery (measured with micropuncture technique) and in the center (measured with wick-in needle technique). Similar to our previous study, IFP rose rapidly and reached maximum values at a depth of 0.2 to 1.0 mm from the tumor surface. These maximum IFP values [16.5 +/- 7.1 mm Hg (SD)] were equal to IFP in the tumor center [18.4 +/- 9.3 mm Hg] [R2 = 0.86, P greater than 0.8]. Superficial MVP (17.3 +/- 6.1 mm Hg) was equal to both central (P greater than 0.9) and superficial IFP (P greater than 0.7). These results demonstrate that the main driving force for IFP in tumors is the MVP. Furthermore, the concept that blood vessel collapse is induced by higher hydrostatic pressures in the tumor interstitium compared to that in the vascular lumen is not supported by the present finding that elevated IFP is accompanied by equally elevated MVP. PMID- 1516069 TI - Unifocal origin of advanced human epithelial ovarian cancers. AB - Ovarian cancers are often diagnosed at a late stage, after the cancer cells have spread to extraovarian sites. Failure to diagnose these tumors earlier may reflect the lack of symptoms and the need for a sensitive, reliable screening test. Alternatively, this can be explained by the hypothesis that some of the extraovarian tumor implants do not represent metastatic spread from the primary cancer but instead are multiple primary tumors developing simultaneously in the peritoneal epithelium. If this is the case, some patients with advanced ovarian cancer may never have had a stage I disease, making early detection theoretically impossible. In this study, we examined the mutational pattern of the p53 gene in 9 patients with epithelial ovarian cancers using tissue collected from different sites within the same patient. In all 9 cases, the mutational pattern of the p53 gene was identical in cancer cells from different sites within the same patient, strongly suggesting that these ovarian tumors were of unifocal origin and that cancer tissues collected from different sites are derived from a single origin. PMID- 1516070 TI - Protection from chemotherapy-induced alopecia by 1,25-dihydroxyvitamin D3. AB - We have previously reported that several biological agents, when given simultaneously with cytosine arabinoside or cytoxan, will protect from cytosine arabinoside-induced but not from cytoxan-induced alopecia. In the present study we used the secosteroid 1,25-dihydroxyvitamin D3 in a different timing schedule to protect from chemotherapy-induced alopecia. In three separate experiments, 0.2 microgram of topical, 1,25-dihydroxyvitamin D3 protected rats from alopecia induced by etoposide, cytoxan, and an Adriamycin-cytoxan combination. In another experiment, 0.1 microgram protected rats from etoposide-induced alopecia at the site of application. 1,25-Dihydroxyvitamin D3 may offer a new and exciting approach to the prevention of chemotherapy-induced alopecia. PMID- 1516072 TI - The role of drugs in the etiology of stroke. AB - Drugs of many classes have been implicated in hemorrhagic and ischemic stroke. Alcohol in moderation may have a protective effect although in greater doses may predispose to stroke. Drugs such as cocaine, amphetamines and heroin have been associated with stroke by a number of mechanisms. Antiplatelet, anticoagulant and thrombolytic therapy carry risk of hemorrhagic complications. Oral contraceptives appear to slightly increase stroke risk whereas estrogen replacement therapy may decrease it. Anabolic steroid use in athletes has been linked to stroke. The antineoplastic agent L-asparaginase has been associated with cerebral hemorrhage, ischemic infarction and venous sinus thrombosis. Infarction has been reported in association with cisplatin-based combination chemotherapy. Stroke is an infrequent but recognized complication of some forms of drug therapy and drug abuse. PMID- 1516071 TI - Radon-induced deletions in human cells: role of nonhomologous strand rejoining. AB - Radon is a ubiquitous inhaled human carcinogen that is thought to be the largest single natural source of human exposure to radiation. We report that a freely replicating episome in human cells exposed to radon gas underwent mutagenic changes, a high proportion of which were large deletions involving many thousands of base pairs. These deletions were not randomly distributed but started and ended in defined regions as if caused by the passage of a single alpha-particle track through a coiled chromatin structure. The sizes appeared to be defined by structural features of chromatin: the minimum size was 2435 base pairs, and the maximum size was 8051 base pairs, close to the upper limit that would leave intact the plasmid sequences required for selection in bacteria. Ends were rejoined by nonhomologous recombination involving up to 6 base pairs of homology. This process may not be confined to the repair of exogenously induced double strand breaks but may be used for rejoining free DNA ends generated by a variety of cellular processes. The mechanism of alpha-particle deletion mutagenesis may account for the high relative biological effectiveness of radon irradiation for many end points and its consequences for lung carcinogenesis. PMID- 1516073 TI - Baclofen in the treatment of dystonia. AB - Dystonia refers to involuntary, prolonged muscle contractions leading to sustained, often twisting, postures. High dose anticholinergic therapy for childhood onset dystonia, botulinum toxin injections for focal dystonia, and levodopa for diurnal dystonia provide symptomatic relief for some patients. Despite this, treatment of both idiopathic and secondary dystonia remains inadequate for many patients. Baclofen, a pre-synaptic acting GABA agonist, has been reported to benefit dystonia in a number of retrospective studies. Dramatic improvement in symptoms, especially in gait, was found in almost 30% of 31 children and adolescents with idiopathic dystonia in one retrospective study using doses ranging from 40 to 180 mg daily. The response to baclofen of adults with focal dystonia is less dramatic. One series of 60 adults with cranial dystonia found sustained benefit in 18%. Smaller series have not consistently found significant benefit in adults. Baclofen has been used to treat several secondary dystonias: tardive dystonia has occasionally been reported to improve and there are isolated reports of improvement in dystonia occurring in Parkinson's disease and in glutaric aciduria. PMID- 1516074 TI - Dihydroergotamine: a review of its use in the treatment of migraine and other headaches. AB - Dihydroergotamine has been one of the main drugs used in the treatment of migraine for greater than 40 years. The recent introduction of the more selective 5-HT antagonist sumatriptan will challenge the place of dihydroergotamine in migraine therapy and indicates the need to review the evidence for the use of dihydroergotamine. Although there is little evidence from double-blind clinical trials, dihydroergotamine does appear to be effective in the treatment of acute attacks and in the prevention of migraine. Its place in treatment is in cases where simple analgesics alone or in combination with other agents fail to provide relief. Further studies are necessary to compare dihydroergotamine with sumatriptan for acute migraine and with beta-blockers in prophylaxis to determine its future role in migraine therapy. PMID- 1516075 TI - Nitrous oxide abuse in perspective. AB - I present evidence that certain health professionals have a higher liability to drug abuse than does the general population. In view of this, data are presented in which the extremely limited contribution of nitrous oxide to this problem is assessed. I demonstrate on the basis of the limited published data now available that pure nitrous oxide addiction is very rare among health professionals, being the rarest drug of abuse among them. When used by the latter, it is most commonly part of a polydrug abuse pattern, not being a major component of the addiction in these cases. It is clear that nitrous oxide addiction is even less of a problem in the general population. Furthermore, after almost 200 years of use, its very minor addictive potential should by now have clarified itself. It would appear that it is unlikely to become, has never been, nor is it the moment of any real significance as a drug of abuse when compared with the many currently available addictive drugs, which clearly pose a much more serious problem. PMID- 1516076 TI - Naloxone attenuates drinking behavior in a schizophrenic patient displaying self induced water intoxication. AB - This study was performed to examine the effect of naloxone on drinking behavior in a schizophrenic inpatient with psychosis, intermittent hyponatremia, and polydipsia (PIP syndrome). His body weight was checked five times daily, and the maximum and minimum weight gains during a day were chosen as an index of polydipsia. Both daily (0.6 mg) and repeated (0.6 mg for 6 days) injections of naloxone suppressed his weight gain significantly for 2 weeks. Withdrawal of the drug for 4 weeks resulted in weight gain recovering to control level. Thereafter, a second trial was performed to examine the long-term effect of this treatment. A daily naloxone (0.6 mg) injection series was performed once every 2 weeks for six series (12 weeks). This drug regimen also suppressed his weight gain in a continuous fashion. The study showed that naloxone seems to be a potential treatment for PIP syndrome and that endogenous opioid systems play a part in the compulsive drinking behavior of the PIP syndrome. PMID- 1516077 TI - Exacerbation of parkinsonism by tacrine. AB - A patient with Alzheimer's disease and mild features of parkinsonism was treated with tacrine. Tremor and gait dysfunction worsened but responded to the addition of levodopa without adversely affecting cognitive function. The implications for experimental treatment strategies of patients with combined Alzheimer's and Parkinson's disease are discussed. PMID- 1516078 TI - Professor Serge David. PMID- 1516079 TI - Analysis of conformationally restricted models for the (1----6)-branch of asparagine-linked oligosaccharides by n.m.r.-spectroscopy and HSEA calculation. AB - The conformational preferences of the trisaccharide, beta-D-GlcpNAc-(1----2) alpha-D-Manp-(1----6)-beta-D-GlcpOR (1) have been investigated by n.m.r. spectroscopy and HSEA calculation. The fixed omega-angle bicyclic analogs 2 and 3, models for the gt and gg rotamers, respectively, of 1, were furthermore examined with the same techniques in an attempt to deduce which of the conformations accessible to 1 was recognized and glycosylated by the enzyme GlcNAc-transferase-V, which acts on a component of the (1----6)-arm of glycoproteins. Only the gg bicyclic 3 was found to be reactive with the enzyme and this study concludes, based on conformational analysis, that 1 as well as the natural Asn-linked oligosaccharide are recognized by GlcNAc-transferase-V in only one of the two local minimum energy conformations energetically accessible to these molecules in their gg rotamer. PMID- 1516080 TI - Special issue in honour of Professor Serge David. PMID- 1516081 TI - Synthesis of C-glycopyranosyl compounds by a palladium-catalyzed coupling reaction of 1-tributylstannyl-D-glucals with organic halides. AB - 1-Tributylstannyl-D-glucals, prepared from the corresponding 1-phenylsulfonyl-D glucals, were coupled efficiently to various organic halides in the presence of a palladium(0) catalyst. This mild reaction is specially useful for the preparation of 1-C-aryl-D-glucals and compatible with unprotected hydroxy groups or hindered aromatic bromides. It has been shown that the resulting 1-C-aryl(alkyl)-D-glucals are suited for further synthetic manipulation of the enol ether group, including stereoselective hydrogenation, hydroboration-oxidation, or epoxidation. All compounds formed resulted from the attack of the alpha-face of the glucal derivatives by the reagent. The reaction, extended to 1,3-, 1,4-di-, and 1,3,5 tri-bromobenzenes, leads to the corresponding symmetrical di-(tri)-C glucosylbenzenes. Finally, a sequential di-C-glucosylation of 1,3-dibromobenzene with two different 1-stannylated glucals was obtained. PMID- 1516082 TI - Synthesis of 2-(4-trifluoroacetamidophenyl)ethyl O-(L-glycero-alpha-D-manno heptopyranosyl)-(1----7)-O-(L-glycero-alpha- D-manno- heptopyranosyl)-(1----3)-L glycero-alpha-D-manno-heptopyranoside, corresponding to the heptose region of the Salmonella Ra core structure. AB - The title trisaccharide was synthesized from methyl 2,3,4-tri-O-benzyl-L-glycero alpha-D-manno-heptopyranoside by acetolysis, followed by conversion into ethyl thioglycosides and also glycosyl bromides, which were both used in glycosylation reactions. In glycosylations using thioglycosides as glycosyl donors, N iodosuccinimide-silver triflate and dimethyl(methylthio)sulfonium triflate were used as promoters, and in glycosylations with glycosyl bromides silver triflate was used. The protecting groups introduced into intermediates during the synthesis of the title trisaccharide were designed to allow later glycosylation at O-3' to give larger oligosaccharide fragments of the Salmonella LPS core region, and also to allow the introduction of phosphate groups at O-4 and O-4', a structural element that is suggested to be present in the Ra core. PMID- 1516083 TI - 4-O-beta-D-galactopyranosyl-D-xylose: a new synthesis and application to the evaluation of intestinal lactase. AB - 4-O-beta-D-Galactopyranosyl-D-xylose (2) was prepared from benzyl 2,3-O isopropylidene-beta-D-xylopyranoside by glycosylation with 2,3,4,6-tetra-O benzoyl-alpha-D-galactopyranosyl bromide and subsequent deprotection. Compound 2 was hydrolyzed in vitro by intestinal lactase; the Vmax was 25% of that with lactose and the Km was 370mM (cf. 27mM for lactose). Oral administration of 2 suckling rats led to urinary excretion of D-xylose which could be estimated colorimetrically. PMID- 1516084 TI - Synthesis of an octasaccharide fragment of high-mannose-type glycans of glycoproteins. AB - O-(alpha-D-Mannopyranosyl)-(1----2)-O-(alpha-D-mannopyranosyl)-(1----3)- O- [(alpha-D-mannopyranosyl)-(1----2)-O-(alpha-D-mannopyranosyl)-(1----6)]- O- (alpha-D-mannopyranosyl)-(1----6)-O-(beta-D-mannopyranosyl)-(1----4)-O-( 2- acetamido-2-deoxy-beta-D-glucopyranosyl)-(1----4)-2-acetamido-2-deoxy- glucopyranose, an octasaccharide fragment of high-mannose type glycan of glycoproteins, was synthesized. Crucial glycosylation of trisaccharide intermediate, benzyl O-(2,4-di-O-benzyl-beta-D-mannopyranosyl)-(1----4)-O-(2 acetamido-3,6-di -O- benzyl-2-deoxy-beta-D-glucopyranosyl)-(1----4)-2-acetamido 3,6-di-O-benz yl-2- deoxy-beta-D-glucopyranoside, was successful only with a di-O acetyltetradeca-O-benzyl-D-mannopentaosyl chloride. The use of the corresponding hexadeca-O-acetyl-D-mannopentaosyl bromide did not give the desired product. PMID- 1516085 TI - [Synthesis of polydeoxygenated and iodinated disaccharides]. AB - 3-Amino-polydeoxy disaccharides have been prepared by condensation of a glycal with methyl 2,3,6-trideoxy-alpha-L-erythro-(or threo)-hex-2-enopyranoside in the presence of N-iodosuccinimide. After acid hydrolysis of the glycoside, 1,4 addition of hydrazoic acid to the corresponding hex-2-enopyranose led to 3-azido disaccharides which were acetylated. Reduction of the azido group gave 2,2' dideoxy- or 2,2'-dideoxy-2'-iodo compounds. Condensation of O-(3,4-di-O-acetyl 2,6-dideoxy-2-iodo-alpha-L-manno-hexopy-rano syl)-(1----4)-1- O-acetyl-2,3,6 trideoxy-3-trifluoroacetamido-alpha-L-arabino-he xopyranose with daunomycinone, followed by 3',4'-O-deacetylation produced the new anthracycline, 7-O-[O-(2,6 dideoxy-2-iodo-alpha-L-manno-hexopyranosyl)-(1----4)-2,3,6- trideoxy-3 trifluoroacetamido-alpha-L-arabino-hexopyranosyl]-da uno-mycinone. PMID- 1516086 TI - Synthesis of aryl D-gluco- and D-galacto-pyranosides and 1-O-acyl-D-gluco- and -D galacto-pyranoses exploiting the Mitsunobu reaction. Influence of the pKa of the acid on the stereoselectivity of the reaction. AB - Glycosides (alpha- and beta-D-glucosides and -D-galactosides) derived from three pesticides, 2-tert-butyl-2,4-dinitrophenol,2,6-dibromo-4-cyanophenol, and 5-(2,4 dichlorophenoxy)-2-nitrobenzoic acid, were synthesized from 2,3,4,6-tetra-O chloroacetyl-D-gluco- and -D-galactopyranose by use of the Mitsunobu reaction. It was shown that selectivity for the beta-D anomer increases with the pKa of the acid component. PMID- 1516087 TI - The synthesis of 5-C-(6-deoxy-1,2:3,4-di-O-isopropylidene-alpha-D-galactopyranos 6-yl)-2 ,3-O-isopropylidene-D-allo-pentofuranose [deaminotri-O-isopropylidene tunicamine]. AB - Three approaches to the synthesis of deaminotunicamine and derivatives were developed. Tin tetrachloride condensation of 6-deoxy-1,2:3,4-di-O-isopropylidene alpha-D-galacto-heptodialdo-1, 5-pyranose with 2-(trimethylsilyloxy)furan gave a mixture of stereoisomeric precursors. Condensation of 1,2:3,4-di-O-isopropylidene alpha-D-galacto-hexodialdo-1,5-pyranos e with the phosphate carbanion obtained from diethyl (2-furyl)methoxymethyl phosphonate led to 6-deoxy-7-C-(2-furyl) 1,2:3,4-di-O-isopropylidene-L-glycero-alpha-D- galactoheptopyranose (13). This was converted, via the "delta 2"-butenolide route, to a mixture of stereoisomeric 5-C-(6-deoxy-alpha-D-galactopyranos-6-yl)-pentono-1,4-lacton es of the D-allo and D-talo configuration. In the third approach, 13 was transformed by the "enulose" approach to deamino-tri-(O-isopropylidene)tunicamine. PMID- 1516088 TI - Synthesis of beta-D-mannosides from beta-D-glucosides via an intramolecular SN2 reaction at C-2. AB - The selective synthesis of beta-D-mannosides was achieved by first synthesizing beta-D-glucosides that carry a N-phenylcarbamoyl protecting group at O-3. These derivatives were transformed into the corresponding beta-D-mannosides by intramolecular nucleophilic substitution with inversion of configuration at C-2, the O-trifyl group being the leaving group. Subsequent intramolecular attack of the neighboring carbamoyl group resulted in the formation of the 2,3-carbonate of the desired beta-D-mannoside. PMID- 1516089 TI - A facile synthesis of nitrophenyl oligosaccharides containing the O-alpha-L fucopyranosyl-(1----3)-2-acetamido-2-deoxy-beta-D-glucopyrano syl unit at their nonreducing end. AB - A facile approach towards the synthesis of 4-nitrophenyl O-alpha-L-fucopyranosyl (1----3)-2-acetamido-2-deoxy-beta-D-glucopyra nos ide, 2-nitrophenyl O-alpha-L fucopyranosyl-(1----3)-O-(2-acetamido-2-deoxy-beta-D-glucop yra nosyl)- (1----6) 2-acetamido-2-deoxy-alpha-D-galactopyranoside, 4-nitrophenyl O-alpha-L fucopyranosyl-(1----3)-O-(2-acetamido-2-deoxy-beta-D-glucop yra nosyl)- (1----6) alpha-D-mannopyranoside, and 4-nitrophenyl O-alpha-L-fucopyranosyl-(1----3)-O-(2 acetamido-2-deoxy-beta-D-glucop yra nosyl)-(1----6)-beta-D-galactopyranoside has been accomplished through the development and use of methyl 3,4-O-isopropylidene 2-O-(4-methoxybenzyl)-1-thio-beta-L-fucopyranoside as the glycosyl donor. PMID- 1516090 TI - Polymers having (1----4)- and (1----6)-linked alpha-D-glucopyranosyl groups as acceptors in the glycogen synthase reaction. AB - Insoluble, light-sensitive polymers linked to maltose, maltotriose, a glycogen branch point trisaccharide, and panose were synthesized and served in a comparative study as acceptors in the glycogen synthase (UDP-D-glucose:glycogen 4 alpha-D-glucosyltransferase, EC 2.4.1.11) reaction. The highest transfer rate was observed with the maltotrio polymer. Extending the acceptor linearly with (1--- 4)-linked alpha-D-glucopyranosyl residues improved the transfer, whereas (1----6) linked alpha-D-glucopyranosyl branches decreased it. PMID- 1516091 TI - Biosynthesis of the blood group Pk and P1 antigens by human kidney microsomes. AB - On human erythrocytes, the membrane components associated with Pk and P1 blood group specificity are glycosphingolipids that carry a common terminal alpha-D Galp-(1----4)-beta-D-Gal unit, the biosynthesis of which is poorly understood. Human kidneys typed for P1 and P2 (non-P1) blood-group specificity have been assayed for (1----4)-alpha-D-galactosyltransferase activity by use of lactosylceramide [beta-D-Galp-(1----4)-beta-D-Glcp-ceramide] and paragloboside [beta-D-Galp-(1----4)-beta-D-GlcpNAc-(1----3)-beta-D-Galp- (1----4)-beta-D-Glcp ceramide] as acceptor substrates. The linkage and anomeric configuration of the galactosyl group transferred into the reaction products were established by methylation analysis before and after alpha- and beta-D-galactosidase treatments, as well as by immunostaining using specific monoclonal antibodies directed against the Pk and P1 antigens. The results demonstrated that the microsomal proteins from P1 kidneys catalyze the synthesis of Pk [alpha-D-Galp-(1----4)-beta D-Galp-(1----4)-beta-D-Glcp-ceramide] and P1 [alpha-D-Galp-(1----4)-beta-D-Galp (1----4)-beta-D-GlcpNAc-(1----3)-beta -D-Galp-(1----4)-beta-D-Glcp-ceramide] glycolipids, whereas microsomes from P2 kidney catalyze the synthesis of the Pk glycolipid, but not of the P1 glycolipid. Competition studies using a mixture of two oligosaccharides (methyl beta-lactoside and methyl beta-lacto-N- neotetraoside) or of two glycolipids (lactosylceramide and paragloboside) as acceptors indicated that these substrates do not compete for the same enzyme in the microsomal preparation from P1 kidneys. The results suggested that the Pk and P1 glycolipids are synthesized by two distinct enzymes. PMID- 1516092 TI - Adverse effects of alkali and acid on the anticoagulant potency of heparin, evaluated with methyl 2-deoxy-2-sulfamino-alpha-D-glucopyranoside 3-sulfate as a model compound. AB - A variety of chemical modifications can induce a reduction in the anticoagulant activity of heparin. Among such modifications are the removal in alkaline solution of the 2-O-sulfonate group of alpha-L-idopyranosyluronic acid 2-sulfate residues (1) and, in a weakly acidic medium, of the N-sulfonate group of residues of 2-deoxy-2-sulfamino-alpha-D-glucopyranose 6-sulfate (2). This study examined the possibility that the losses in anticoagulant potency are related to a concomitant removal of the 3-O-sulfonate group of residues of 2-deoxy-2-sulfamino alpha-D-glucopyranose 3,6-disulfate (6) in the AT-III binding site. It entailed a synthesis of methyl 2-deoxy-2-sulfamino-alpha-D-glucopyranoside 3-sulfate (7), as a model compound that was subjected to both the strongly alkaline and weakly acidic conditions appropriate for the modification of residues 1 and 2, respectively. The 3-sulfate group of 7 was found to be highly stable in both environments. This indicated that the adverse effects that these conditions have on the anticoagulant properties of heparin are not specifically associated with the 3-sulfate substituent of residues of 6 in the polymer. PMID- 1516093 TI - Synthesis of 6'-S-alpha-D-glucopyranosyl-6'-thiomaltose (6(2)-thiopanose) and its effect on the enzymic activity of glucoamylases from Aspergillus niger. PMID- 1516094 TI - Positional isomers of thioxylobiose, their synthesis and inducing ability for D xylan-degrading enzymes in the yeast Cryptococcus albidus. AB - Isomeric S-linked 2-thioxylobiose 10, 3-thioxylobiose 17, and 4-thioxylobiose 19 were conveniently prepared by SN2 displacement of suitable triflylglycoses with the sodium salt of 2,3,4-tri-O-acetyl-1-thio-beta-D-glucopyranose, either in N,N dimethylformamide, or in oxolan in the presence of a sodium complexing agent. Allyl 3,5-O-isopropylidene-2-O-trifluoromethanesulfonyl-beta-D-lyxofu ranoside was a convenient electrophilic precursor for 10, which was smoothly obtained after a short sequence of deprotection involving conversion to the 1-propenyl glycoside. 1,2:5,6-Di-O-isopropylidene-3-O-trifluoromethylsulfonyl-alpha-D-++ +allofuranose and 1,2,3-tri-O-benzoyl-4-O-trifluoromethylsulfonyl-beta-L-arabinop yranose were the respective precursors for 17 and 19. 4-Thioxylobiose has a highly stimulatory effect on the synthesis of enzymes of the xylanolytic system in the yeast Cryptococcus albidus when applied to the cells in the presence of the natural disaccharide inducer (1----4)-beta-D-xylobiose. PMID- 1516095 TI - The preparation and phosphorylation of 2,5- and 1D-2,6-di-O-benzyl-myo-inositol. AB - 1,3,4,6-Tetra-O-allyl-myo-inositol was converted into the 2,5-di-O-benzyl- and 2,5-di-O-p-methoxybenzyl ethers, and the products were deallylated to give the 2,5-di-O-benzyl (and p-methoxybenzyl) ethers of myo-inositol, which were converted into the mono-O-isopropylidene derivatives. Both the 2,5-di-O-benzyl ether and its mono-O-isopropylidene derivative were converted into the crystalline octa(2-cyanoethyl) ester of 2,5-di-O-benzyl-myo-inositol 1,3,4,6 tetrakisphosphate. (+-)-1,3,4,5-Tetra-O-allyl-myo-inositol was converted into (+ )-2,4-di-O-benzyl-myo-inositol which gave a separable mixture of the 1,6- and 5,6 O-isopropylidene derivatives. The 1,6-O-isopropylidene derivative was resolved via (-)- and (+)-omega-camphanates and was also converted into (+-)-2,6-di-O benzyl-1,5-di-O-p-methoxybenzyl-myo-inositol, which was resolved via the (-) omega-camphanates. The 5,6-O-isopropylidene derivative and 1,3-di-O-allyl-myo inositol were converted into (+-)-1,3-di-O-allyl-2,6-di-O-benzyl-myo-inositol, which was resolved as the (-)-omega-camphanates. 1D-1,3,4,5-Tetra-O-allyl-myo inositol and the above described, relevant diaste reoisomers were converted into 1D-2,6-di-O-benzyl-myo-inositol which gave the syrupy octabenzyl ester of 1D-2,6 di-O-benzyl-myo-inositol 1,3,4,5-tetrakisphosphate. PMID- 1516096 TI - Selective protections on 2-allyloxycarbonylamino-1,6-anhydro-2-deoxy-beta-D glucopyranose. AB - Regioselective monoacetylation of 2-allyloxycarbonylamino-1,6-anhydro-2-deoxy beta-D-glucopyranose (1) gave a mixture of 3-O-acetyl and 4-O-acetyl derivatives, the structures of which were established by two-dimensional, phase-sensitive NOESY and confirmed by chemical proofs. The benzylation of 1, on the other hand, led to 2-allyloxycarbonylamino-1,6-anhydro-3,4-di- (5) or 2-allyloxycarbonylamino 1,6-anhydro-2-N-benzyl-3,4-di-O-benzyl-2-d eoxy-beta-D- glucopyranose (10). The regioselective cleavage of 5 with titanium tetrachloride gave the expected 3-O benzyl derivative, the structure of which was ascertained by chemical proofs; the same reaction performed on 10 led to the opening of the anhydro ring to afford 3 benzyl-[3,4-di-O-benzyl-1,2-dideoxy-alpha-D-glucopyrano]-[2,1-d] -2- oxazolidone. PMID- 1516097 TI - Synthesis and biological activity of a fluorketonulceoside: 7-(3-deoxy-3-fluoro beta-D-glycero-hex-2-enopyranosyl-4-ulose) theophylline. PMID- 1516098 TI - Methyl-3-O-(2-acetamido-2-deoxy-6-thio-beta-D-glucopyranosyl)-beta- D galactopyranoside: a slow reacting acceptor-analogue which inhibits glycosylation by UDP-D-galactose-N-acetyl-D-glucosamine-(1----4)-beta-D-galactosyltra nsf erase. PMID- 1516099 TI - The crystal structure of the inclusion complex of cyclomaltoheptaose (beta cyclodextrin) with 4-tert-butyltoluene. AB - The crystal of the 1:1 complex of 4-tert-butyltoluene with cyclomaltoheptaose (beta-cyclodextrin, beta CD) is triclinic P1 with a = 15.562(2), b = 15.564(4), c = 15.835(3) A, alpha = 102.11(2), beta = 102.15(1), gamma = 103.64(2) degrees, V = 3505(1) A3, and Z = 2. The two independent beta CD molecules in the asymmetric unit form a dimer by hydrogen bonding involving HO-3, which accommodates two molecules of the guest. The hydrophobic guests are enclosed completely in the beta CD cavities with the tert-butyl groups in the hydrophobic region beneath the primary hydroxyl groups. The aromatic rings have two orientations and their toluene methyl moieties could not be located but were calculated to be at the interface of the two monomers. The dimers form channels along the c axis. The inter-dimer space is filled with 17 molecules of water distributed over 25 sites. A dense network of hydrogen bonds is formed, involving the beta CD hydroxyl groups and water molecules. PMID- 1516100 TI - Synthesis of 2-O-(2-acetamido-2-deoxy-beta-D-glucopyranosyl)-5a-carba-alpha-D- mannopyranose, and 5a-carba-2-O- and 3,6-di-O-(alpha-D-mannopyranosyl)-alpha-D mannopyranoses. AB - Protected derivatives of the title carba-trisaccharide 1, and carba-disaccharides 4 and 6 have been synthesised by conventional glycosylation of the precursors 8, 9, or 22 of 5a-carba-alpha-D-mannopyranose with sugar halides. These are carba sugar analogues of the oligosaccharide chains frequently occurring as structural units in biologically important glycoconjugates, and could be utilised as the building blocks for construction of higher carba-oligosaccharides of biological interest. PMID- 1516101 TI - Synthesis and characterization of highly substituted deoxyfluorocellulose acetate. AB - Deoxyfluorocellulose acetates were prepared from cellulose acetate (CA, degree of substitution by acetyl groups: 2.2 and 1.7) by using diethylaminosulfur trifluoride (DAST) in 1,4-dioxane or diglyme. The maximum degree of substitution of fluorine of the products was approximately 0.60, and depolymerization was not significant during fluorination. The replacement of hydroxyl groups by fluorine atoms occurred exclusively at C-6, as confirmed by carbon-13 NMR spectroscopy. In the presence of pyridine, an N-pyridinium derivative of CA was obtained instead of a deoxyfluoro derivative of cellulose. PMID- 1516102 TI - Phase transfer catalyzed synthesis of 4-nitrophenyl 1-thio-beta-D-glycobiosides. PMID- 1516103 TI - Synthesis of a repeating pentasaccharide fragment of the capsular polysaccharide of Streptococcus pneumoniae type 18C. PMID- 1516104 TI - Preparation of building blocks for carba-oligosaccharides related to cell-surface glycans. PMID- 1516105 TI - Molecular and crystal structure of konjac glucomannan in the mannan II polymorphic form. AB - A probable crystal structure of konjac glucomannan (mannose:glucose ratio = 1.6) is proposed based on X-ray data and constrained linked-atom least-squares model refinement. The structure crystallizes in the mannan II polymorphic form, in an orthorhombic unit-cell with a = 9.01 A, b = 16.73 A, c (fiber axis) = 10.40 A, and a probable space group I222. The backbone conformation of the chain is a two fold helix stabilized by intramolecular O-3-O-5' hydrogen bonds, with the O-6 rotational position gt. The unit cell contains four chains with antiparallel packing polarity and eight water molecules which reside in crystallographic positions. Intermolecular hydrogen bonds occur exclusively between chains and water molecules, establishing a three-dimensional hydrogen-bond network in the crystal structure. The glucose residues replace mannoses in the structure in isomorphous fashion, although some disorder appears possible. A structure having alternating gg-gt O-6 rotational positions and conforming to space group P222 appears to describe the disorder regions of the crystal. The reliability of the structure analysis is indicated by the X-ray residuals R = 0.276 and R" = 0.223. PMID- 1516106 TI - Molecular and crystal structure of the regenerated form of (1----3)-alpha-D mannan. AB - The crystal structure of the hydrated form of (1----3)-alpha-D-mannan, obtained by solid-state deacetylation of the partially O-acetylated mannan, was analyzed by combined X-ray diffraction and stereochemical-model refinement techniques. The structure crystallizes in a four-chain, monoclinic unit cell with parameters a = 11.33 A, b = 18.36 A, c (fiber repeat) = 8.25 A, and gamma = 101.75 degrees, and the most probable space group is P2(1). In the most probable structure the chain backbone conformation is a two-fold helix, but with all four O-6 rotational positions nonequivalent. The chains pack with antiparallel polarity and are connected by pairs of intermolecular hydrogen bonds that form an infinite, zig zag sheet. There are 16 water molecules in the unit cell, generally embedded between the sheets in crystallographic positions, providing additional hydrogen bonding and establishing a three-dimensional hydrogen-bond network in the crystal structure. The reliability of the structure analysis is indicated by the X-ray residual R" = 0.281, based on 98 hkl reflection intensities. PMID- 1516107 TI - Myocardial stunning: a role for calcium antagonists during ischaemia? PMID- 1516108 TI - Myocardial stunning: a role for calcium antagonists during reperfusion? PMID- 1516109 TI - Plasma platelet activating factor degradation and serum lipids after coronary bypass surgery. AB - OBJECTIVE: Platelet activating factor (PAF) is a potent mediator in inflammatory responses and maybe involved in various disease states. Degradation of PAF in plasma results from the action of a specific, lipoprotein associated, acetylhydrolase. The aim was to determine plasma acetylhydrolase activity under optimised conditions, PAF half life, phospholipase A2 activity, the lyso derivative of PAF (lyso-PAF), and lipids in patients undergoing coronary artery bypass grafting. METHODS: The study variables were determined 3 d and 7 d following coronary artery surgery and compared to presurgical values in 15 males, age 55(SEM 4) years. RESULTS: Three days following coronary bypass grafting, total, LDL and HDL cholesterol fell significantly by 30%, 45%, and 15% respectively (p less than 0.001), all decreases correlating with bypass time (p less than 0.025). Concentrations remained low at 7 d (p less than 0.005). Acetylhydrolase activity fell by 38% (p less than 0.001) at 3 d post-surgery and remained depressed, but plasma PAF half life did not change after surgery. The inverse relationship between acetylhydrolase activity and plasma PAF half life preoperatively (p less than 0.01) was not evident after surgery. There was a direct linear relationship between acetylhydrolase activity and both total (p less than 0.002) and LDL cholesterol (p less than 0.001) before surgery. The fall in acetylhydrolase activity correlated with the fall in these lipids (p less than 0.01) but not with that of HDL cholesterol. Plasma lyso-PAF decreased by 65% (p less than 0.001) at 3 d and remained depressed (p less than 0.001). Plasma phospholipase A2 activity increased by 60% (p less than 0.01) and remained raised (p less than 0.05), the increase at 3 d being related to bypass time (p less than 0.05). CONCLUSIONS: The large fall in plasma acetylhydrolase activity after coronary bypass grafting is consistent with the fall in plasma lipids. However, the absence of a significant change in the measured PAF half life in plasma raises questions as to the pathophysiological significance of the decrease in acetylhydrolase activity. PMID- 1516110 TI - Developmental changes in myocardial contractile responses to inotropic agents. AB - Although substantial information has accumulated over the past decade, many gaps remain in our understanding of the regulation of contractility and modulation of inotropic responsiveness in the developing heart. There are several important problems facing investigators in the field of developmental cardiology. Responses often differ among species and the human correlates to many of the animal studies remain to be defined. In many instances, the supply of tissues is limited and difficult to obtain consistently. Furthermore, comparable experiments may be nearly impossible to perform in human fetal and neonatal myocardium. Interpretation of results from developmental studies using various animal species and a number of different experimental models is further complicated by the complexity of normal developmental processes. Numerous changes are occurring simultaneously in neurohumoral influences, cardiac ultrastructure, protein synthesis, gene expression, and metabolism. Comprehensive integration of the impact of these and other factors on overall contractile performance and inotropic responsiveness requires a multifaceted approach incorporating a variety of techniques. Results from pharmacological experiments must be placed into perspective with available knowledge of relevant morphological, physiological, and biochemical status at the precise age in the particular species in which the experiments are performed. A thorough understanding of developmental cardiology is of more than simple academic interest. Basic knowledge of the regulation of contractile function during development will obviously have important therapeutic applications in the immature heart. Moreover, results from future developmental studies directed toward characterising myocardial gene expression, modulation of specific effector systems, and regulation of excitation-contraction coupling are ultimately likely to contribute to the design of therapeutic strategies for both congenital and acquired heart disease. PMID- 1516112 TI - Protective and pathological roles of nitric oxide in endotoxin shock. AB - OBJECTIVE: The aim was to investigate the effects of NG-monomethyl-L-arginine (L NMMA), an inhibitor of both the constitutive (Ca2+ dependent) and inducible (Ca2+ independent) nitric oxide (NO) synthases, or of pretreatment with the glucocorticoid dexamethasone, an inhibitor of the induction of the Ca2+ independent NO synthase, on lipopolysaccharide induced shock in the anaesthetised rabbit. METHODS: Mean arterial blood pressure, and blood flow in the portal vein, hepatic artery, and hindquarter vascular beds were measured in 49 halothane anaesthetised New Zealand White rabbits given lipopolysaccharide (Salmonella minnesota, 500 micrograms.kg-1 intravenously). The effects of pre- or post lipopolysaccharide treatment with L-NMMA (300 mg.kg-1 intravenously) and of pretreatment with dexamethasone (3 mg.kg-1 intravenously) were determined. The effect of the NO donor S-nitroso-N-acetyl-penicillamine (SNAP, 300 micrograms.kg 1.h-1 intravenously) in animals treated with lipopolysaccharide and L-NMMA was also studied. RESULTS: Lipopolysaccharide elicited an initial transient fall in mean arterial pressure and decreases in blood flow in the vascular beds, followed by a progressive fall in mean arterial pressure. L-NMMA when given either before or after lipopolysaccharide markedly exacerbated its effects and resulted in severe hypotension, intense vasoconstriction, and increased mortality. Pretreatment with dexamethasone had no effect on the initial haemodynamic changes following lipopolysaccharide, but prevented the subsequent fall in mean arterial pressure observed in animals treated with lipopolysaccharide alone. Dexamethasone failed, however, to protect animals also treated with L-NMMA before lipopolysaccharide. Animals pretreated with L-NMMA and SNAP showed reduced haemodynamic changes when compared with controls (lipopolysaccharide only) or lipopolysaccharide and L-NMMA treated animals. CONCLUSIONS: Inhibition of both constitutive and inducible NO synthases during endotoxaemia is deleterious. This can be overcome by replacing NO intravenously with a donor of NO. Selective inhibition of the inducible NO synthase may, however, be beneficial in shock. PMID- 1516111 TI - Can myocardial contrast echo determine coronary flow reserve? AB - OBJECTIVE: The aim was to evaluate the applicability of myocardial contrast echocardiography in the measurement of coronary flow reserve. METHODS: Eleven anaesthetised open chest pigs were studied, in which coronary atherosclerosis had been induced by abrasion of the left anterior descending coronary artery at one month, followed by an atherogenic diet for eight months. Coronary flow reserve was determined by electromagnetic flow measurement and contrast echocardiography before and after partial occlusion of the left anterior descending coronary artery, using papaverine as a coronary vasodilator. Coronary blood flow was reduced by tightening a clamp placed around the coronary artery. Systemic haemodynamics and myocardial wall thickness (epicardial ultrasound 5 MHz transducer) were recorded simultaneously. Echocardiograms were recorded on VHS tape and analysed by digitised videodensitometry off line for construction of the time v videointensity curve (time-intensity curves). From these curves washout time (T50), area under the curve, peak contrast intensity, and time to peak intensity were calculated. RESULTS: Following papaverine, coronary blood flow increased significantly from 47 (SD 23) ml.min-1 at baseline to 88(39) ml.min-1 (p less than 0.05). During the stenosis, flow decreased to 19(16) ml.min-1 (p less than 0.01), and increased to 38(29) ml.min-1 (p less than 0.05 v stenosis) after administration of papaverine. Correlations between coronary blood flow and indices calculated from the quantitative videodensitometric analysis were poor, varying between r = 0.03 for area at control flow to r = 0.62 for T50 during stenosis. The same was true for coronary flow reserve: r = 0.09 for peak to r = 0.75 (p less than 0.05) for time to peak without the stenosis. CONCLUSIONS: Current limitations in injection, imaging, and analysis techniques cause variability in data from time-intensity curves, which precludes accurate quantification of coronary flow (reserve) by myocardial contrast echocardiography. PMID- 1516113 TI - Iron availability and free radical induced injury in the isolated ischaemic/reperfused rat heart. AB - OBJECTIVE: A proposal that injury in ischaemic/reperfused rat heart is critically dependent on the availability of free iron rather than on the efficiency of O2-. and H2O2 production was examined. METHODS: Isolated working rat hearts from 152 male Wistar rats (200-250 g weight), subjected to 20-40 min of global ischaemia and reperfused for 30 min, were perfused with 10 mumol.litre-1 Fe[III] or Fe[II] and/or 0.6 mmol.litre-1 desferrioxamine, 10 mmol.litre-1 dimethylthiourea, and 1 mmol.litre-1 allopurinol. Curves relating the recoveries of haemodynamic functions and the reperfusion lactate dehydrogenase release to the duration of the preceding ischaemic period were constructed. Morphological examination was also performed. RESULTS: In the untreated hearts, the duration of ischaemia resulting in 50% loss of cardiac output was 29 min. This time was decreased to 24 min and 20 min by Fe[III] and Fe[II], respectively, and was increased to 36 min and 37 min by desferrioxamine and dimethylthiourea, respectively. Desferrioxamine prevented the effect of Fe[III] but not that of Fe[II], whereas dimethylthiourea prevented the effect of Fe[II]. Neither the effect of Fe[III] nor that of Fe[II] was prevented by allopurinol which, however, proved to be beneficial in the untreated hearts. CONCLUSIONS: The beneficial effect of desferrioxamine and dimethylthiourea suggest that it is intensification of the Fenton reaction by iron which accounts for iron induced aggravation of the reperfusion injury. Thus we speculate that the availability of free iron, rather than O2-. and H2O2, is a limiting factor in the development of injury in an ischaemic/reperfused rat heart. What remains unclear is why allopurinol is unable to prevent iron induced changes. PMID- 1516114 TI - Effect of antiarrhythmic drugs on choline uptake in cardiac cells in culture. AB - OBJECTIVE: The aim was to examine the effect on choline uptake of various antiarrhythmic drugs: lignocaine, tocainide, encainide, flecainide, propafenone, procainamide, N-acetylprocainamide, bretylium, and amiodarone. METHODS: Cardiac ventricular myocytes from 7 d old chick embryos were exposed in culture to these drugs, at concentrations ranging from 10(-6) to 10(-4) M, for 24 h. Myocyte choline uptake was assessed by the addition of methyl [3H] choline to media. After 120 min, media were removed, the cells were harvested, and intracellular [3H] actively was counted. RESULTS: Lignocaine and tocainide produced a significant (p less than 0.05) dose dependent increase in intracellular [methyl 3H] choline. Encainide produced a small increase and flecainide a small decrease in choline, neither of which was dose dependent. Propafenone significantly (p less than 0.05) altered choline uptake: at 10(-6) M and 10(-5) M choline uptake was increased and at 10(-4) M it was decreased. Amiodarone produced a marked and significant (p less than 0.05) dose dependent reduction in choline uptake. Bretylium, procainamide, and N-acetylprocainamide did not alter myocyte choline. CONCLUSIONS: Choline incorporation into cardiac myocyte is altered by some antiarrhythmic drugs, suggesting this may be part of their antiarrhythmic properties. PMID- 1516115 TI - Calcium antagonists and the stunned myocardium: a role during ischaemia? A role during reperfusion? PMID- 1516116 TI - Effects of fenfluramine on the metabolism of calcium and phosphorus in the rat: fenfluramine effects on Ca and P metabolism. AB - Daily administration of 2, 5, 10, 15 and 20mg of fenfluramine/kg body weight to adult rats for four weeks resulted in dose dependent decrease in calcium and phosphorus absorption with an inverse correlation of r = -0.94 for calcium and r = -0.93 for phosphorus. Significant (P less than 0.05) increase in the total faecal lipids and moderate decline in plasma calcium levels were also observed in the rats. Adult rats made obese by dietary methods when treated with 10mg and 15 mg of fenfluramine/kg body weight/day for 10 weeks showed a significant reduction (p less than 0.001) in the intestinal absorption of both calcium and phosphorus. The reduction at 15mg/kg drug dose was 10.7 pc for calcium and 9.5 pc for phosphorus. Analyses of the long bones as well as carcasses of the obese rats showed significant decrease (p less than 0.001) in the content of these minerals. Plasma calcium and phosphorus levels were also significantly (p less than 0.001) reduced in the obese-treated rats. However, fenfluramine treatment significantly reduced the plasma calcium but not the phosphorus levels in the non-obese rats. These studies have demonstrated that chronic administration of fenfluramine (greater than or equal to 10mg/kg body weight) to rats, obese or non-obese, impairs calcium and phosphorus metabolism in the body. PMID- 1516117 TI - Carcinoma of penis in Zambia: associated problems in management. AB - Thirty-three case reports of patients with carcinoma of penis were scrutinised at the University Teaching Hospital, Lusaka, Zambia to look into the associated environmental problems causing an unacceptable level of morbidity and mortality. Due to social and personal reasons, late presentation and poor follow-up is common. Improvement in the poor outcome is only possible with change in social attitudes and alleviation of ignorance. Educating traditional healers will help. For the present radiotherapy may be the other option to improve the morbidity and survival rates in this potentially a curable cancer. PMID- 1516118 TI - Fever, cytokines and shock. AB - Septic shock is a complex event with activation of many inflammatory pathways. Recent advances have begun to make some sense of the pathophysiological events. This review describes the historical background to the contemporary concepts and outlines the important role that cytokines probably have in the pathophysiology of septic shock. A consequence of the changing understanding of septic shock is that new therapeutic interventions are becoming available. PMID- 1516119 TI - Advances in lymphoma treatment. AB - There have been considerable advances in the management of patients with lymphoma over the past three decades. In Hodgkin's disease, there was a major break through in the late 1960s with the development of the MOPP combination regimen. Using this and other more recent combinations, remission rates of up to 80 pc may be achieved overall with many patients having durable remissions. In non Hodgkin's lymphoma there have been few advances in therapy of the indolent low grade varieties which remain largely incurable. In the aggressive high-grade lymphomas, some subtypes have proved highly responsive to intensive cytotoxic programmes, giving remission rates and relapse-free survival rates of 70-80 pc. Certain categories, however, such as lymphoblastic lymphoma, remain a problem. Bone marrow transplantation and biological response modifiers have been important recent developments. The search for treatment strategies that improve survival and have relatively low toxicity is a continuing challenge. PMID- 1516120 TI - Schistosomiasis of the testis. AB - Bilhazial orchitis is still rare in many countries, and when it presents, difficulties in diagnosis arise. Since it stimulates testicular cancer, misdiagnosis invariably leads to orchiectomy, an unfortunate event in the young patient. PMID- 1516121 TI - Giant inguino scrotal hernia: a case report. AB - Giant inguino--scrotal hernia is largely a problem of developing countries. A case of an unusually giant inguino-scrotal hernia is reported highlighting the problems encountered in management. Orchidectomy, bowel resection and relaxing epigastric incision were successfully employed in repairing the hernia. Hernias may not be difficult to manage if they ar not neglected. Efforts of health education need intensifying in this direction. We propose thorough peri-operative pulmonary exercises to cut down the post-operative pulmonary morbidity. PMID- 1516122 TI - An unusual cervical adenosis. AB - A 57-year-old woman with a mass on the uterine cervix was presented. Her complaint was persistent leukorrhea and treated by hysterectomy because of cervical mass. The histologic diagnosis was adenosis of the cervix. It is believed that this is the first report of benign adenosis of cervix in this size in woman who was not exposed to Diethylstilbestrol in utero. PMID- 1516123 TI - Use of loperamide hydrochloride in children. PMID- 1516124 TI - The Mpilo dilemma. PMID- 1516125 TI - Fighting cancer in the 21st century. PMID- 1516126 TI - Zimbabwe National Cancer Registry: summary data 1986-1989. National Cancer Registry Advisory Committee. AB - The Zimbabwe National Cancer Registry began operation in 1986. Between 1986-1989, a total of 8 276 cases were identified. Among men of African descent, oesophageal (11.2 pc) and liver cancer (11.0 pc) were most common. Cervical cancer was by far the most common among women of African descent (34.5 pc). Among both males and females of non-African descent, skin cancers (other than melanoma) accounted for one-third of cancers followed by prostate cancer (7.7 pc) in males and breast cancer (18.5 pc) in females. These findings are comparable to earlier reports of the epidemiology of cancer in Zimbabwe. PMID- 1516127 TI - A three-year prospective study of 137 cases of acute leukaemia in Zimbabwe. AB - We studied 137 cases of acute leukaemia seen between December 1985 and November 1988, using traditional staining techniques together with cytochemistry and in cases of probable acute lymphoblastic leukaemia (Sudan Black negative) by immunophenotyping. Not all tests were carried out in every case (some cases of ALL could only be classified as T or non-T). Paediatric group (age less than or equal to 14 yrs): 75 cases--acute lymphoblastic leukaemia 52, acute myeloid leukaemia 18, acute undifferentiated leukaemia 5. Peak incidence in 5-9 year group. Male:Female ratio = 1.7:1. acute myeloid leukaemia was associated with chloromas in 2 cases (11 pc). Adult group: 62 cases--acute lymphoblastic leukaemia 23, acute myeloid leukaemia 36 and acute undifferentiated leukaemia 3. Peak incidence in 50-54 age group. Male:Female ratio = 1:1.2. Acute lymphoblastic leukaemia subtypes (all ages) T 16, Common 20, Null 12, 'non-T' 16, B cell 0, untyped 11. 69 pc were of L2 morphology. In T-ALL, 11 had thymomas and Male:Female ratio = 15:1. Male:Female ratio for 'non-T' = 1.5:1. Acute myeloid leukaemia subtypes (all ages) M1 3, M2 8, M3 14, M4 19, M5 8, M6 2, M7 1. Overall incidence of acute leukaemia appears increased at 0.91 per 100,000 per annum from previous studies in Zimbabwe. Common ALL (mean age = 13 years) is an emerging problem and now outnumbers T-ALL (mean age = 10 years). This may be related to a general improvement in living standards and health in Zimbabwe. PMID- 1516128 TI - Dynamic mutations: a new class of mutations causing human disease. PMID- 1516129 TI - Retraction: renaturation of denatured lambda repressor requires heat shock proteins. PMID- 1516130 TI - The small GTPase rab5 functions as a regulatory factor in the early endocytic pathway. AB - We have investigated the in vivo functional role of rab5, a small GTPase associated with the plasma membrane and early endosomes. Wild-type rab5 or rab5 ile133, a mutant protein defective in GTP binding, was overexpressed in baby hamster kidney cells. In cells expressing the rab5ile 133 protein, the rate of endocytosis was decreased by 50% compared with normal, while the rate of recycling was not significantly affected. The morphology of early endosomes was also drastically changed by the mutant protein, which induced accumulation of small tubules and vesicles at the periphery of the cell. Surprisingly, overexpression of wild-type rab5 accelerated the uptake of endocytic markers and led to the appearance of atypically large early endosomes. We conclude that rab5 is a rate-limiting component of the machinery regulating the kinetics of membrane traffic in the early endocytic pathway. PMID- 1516131 TI - The small GTP-binding protein rab4 controls an early sorting event on the endocytic pathway. AB - rab4 is a ras-like GTP-binding protein that associates with early endosomes in a cell cycle-dependent fashion. To determine its role during endocytosis, we generated stable cell lines that overexpressed mutant or wild-type rab4. By measuring endocytosis, transport to lysosomes, and recycling, we found that overexpression of wild-type rab4 had differential effects on the endocytic pathway. Although initial rates of internalization and degradation were not inhibited, the transfectants exhibited a 3-fold decrease in fluid phase endocytosis as well as an alteration in transferrin receptor (Tfn-R) recycling. Wild-type rab4 caused a redistribution of Tfn-R's from endosomes to the plasma membrane. It also blocked iron discharge by preventing the delivery of Tfn to acidic early endosomes, instead causing Tfn accumulation in a population of nonacidic vesicles and tubules. rab4 thus appears to control the function or formation of endosomes involved in recycling. PMID- 1516132 TI - Defective T cell receptor signaling in mice lacking the thymic isoform of p59fyn. AB - Considerable evidence supports the hypothesis that the nonreceptor protein tyrosine kinase p59fyn participates in signal transduction from the T cell receptor (TCR). To examine this hypothesis in detail, we have produced mice that lack the thymic isoform of p59fyn but retain expression of the brain isoform of the protein. fynTnull mice exhibit a remarkably specific lymphoid defect: thymocytes are refractile to stimulation through the TCR with mitogen or antigen, while peripheral T cells, following what appears to be a normal maturation sequence, reacquire significant signaling capabilities. These data confirm that p59fynT plays a pivotal role in TCR signal transduction and demonstrate that additional developmentally regulated signaling components also contribute to TCR induced lymphocyte activation. PMID- 1516133 TI - A novel 145 kd brain cytosolic protein reconstitutes Ca(2+)-regulated secretion in permeable neuroendocrine cells. AB - The regulated secretory pathway is activated by elevated cytoplasmic Ca2+; however, the components mediating Ca2+ regulation have not been identified. In semi-intact neuroendocrine cells, Ca(2+)-activated secretion is ATP- and cytosol protein-dependent. We have identified a novel brain protein, p145, as a cytosolic factor that reconstitutes Ca(2+)-activated secretion in two neuroendocrine cell types. The protein is a dimer of 145 kd subunits, exhibits Ca(2+)-dependent interaction with a hydrophobic matrix, and binds phospholipid vesicles, suggesting a membrane-associated function. A p145-specific antibody inhibits the reconstitution of Ca(2+)-activated secretion by cytosol, indicating an essential role for p145. The restricted expression of p145 in tissues exhibiting a regulated secretory pathway suggests a key role for this protein in the transduction of Ca2+ signals into vectorial membrane fusion events. PMID- 1516134 TI - Casein kinase II is a negative regulator of c-Jun DNA binding and AP-1 activity. AB - c-Jun, a major component of the inducible transcription factor AP-1, is a phosphoprotein. In nonstimulated fibroblasts and epithelial cells, c-Jun is phosphorylated on a cluster of two to three sites abutting its DNA-binding domain. Phosphorylation of these sites inhibits DNA binding, and their dephosphorylation correlates with increased AP-1 activity. We show that two of these sites, Thr-231 and Ser-249, are phosphorylated by casein kinase II (CKII). Substitution of the third site, Ser-243, by Phe interferes with phosphorylation of the inhibitory sites in vivo and by purified CKII in vitro. Microinjection into living cells of synthetic peptides that are specific competitive substrates or inhibitors of CKII results in induction of AP-1 activity and c-Jun expression. Microinjection of CKII suppresses induction of AP-1 by either phorbol ester or an inhibitory peptide. These results suggest that one of the roles of CKII, a major nuclear protein kinase with no known functions, is to attenuate AP-1 activity through phosphorylation of c-Jun. PMID- 1516135 TI - MacMARCKS, a novel member of the MARCKS family of protein kinase C substrates. AB - MARCKS is a specific protein kinase C (PKC) substrate that binds both calmodulin and actin and is phosphorylated during phagocyte activation, neurosecretion, and growth factor-dependent mitogenesis. We report here on MacMARCKS, a MARCKS homolog, whose synthesis is dramatically increased in macrophages when these cells are exposed to bacterial lipopolysaccharide. We have purified rabbit MacMARCKS and cloned its cDNA from rabbit and mouse. The effector domains of MacMARCKS and MARCKS are nearly identical, and both proteins bind calmodulin in a phosphorylation-regulated manner. MacMARCKS and MARCKS also share a second, highly conserved region also found in the internalization domain of the mannose-6 phosphate receptor. Our data suggest the existence of a family of PKC substrates that are targeted to different subcellular locations and that function to integrate PKC and calcium/calmodulin-dependent signals in the control of the plastic actin cytoskeleton. PMID- 1516136 TI - Overexpression of oskar directs ectopic activation of nanos and presumptive pole cell formation in Drosophila embryos. AB - In Drosophila, a small group of maternal effect genes, including oskar, defines a shared pathway leading to the provision of two determinants at the posterior pole of the embryo. One determinant is the posterior body patterning morphogen nanos, and the other directs germ cell formation. Overexpression of oskar causes the shared pathway to be hyperactivated, with excess nanos activity present throughout the embryo and a superabundance of posterior pole cells. In addition, presumptive pole cells appear at a novel anterior position. Strikingly, formation of these ectopic pole cells is enhanced in nanos mutants. This observation may reflect competition between nanos and the germ cell determinant for a shared and limiting precursor. PMID- 1516137 TI - Glycerol alters cytoskeleton and cell adhesion while inhibiting cell proliferation. AB - Our previous studies with various cell lines and human glioma cells showed that glycerol suppresses cell proliferation. In this study, we examined the effects of glycerol on the cytoskeleton, general morphology and attachment of Baby Hamster Kidney (BHK) cells. In glycerol-treated cells proliferation was suppressed, the microfilament network was extensively reorganized and the microtubule network was more clearly defined, while the cell thickness, as observed by scanning electron microscopy (SEM), was decreased. In addition, glycerol treatment resulted in an increase in the number of nucleoli per cell and in the appearance of non-mitotic rounded cells. Glycerol treatment increased the time needed to trypsinize BHK cells from the culture dishes and reduced the time required for cell reattachment. We suggest that glycerol treatment provides a non-toxic tool to examine mechanisms of proliferation arrest. PMID- 1516138 TI - Degradation of cytoskeletal proteins by the human immunodeficiency virus type 1 protease. AB - Triton X-100-extracted human skin fibroblasts were exposed to human immunodeficiency virus type 1 protease and analysed by 2D-gel electrophoresis and immunofluorescence microscopy. Vimentin, two of the tropomyosin isoforms, a protein with M(r) approximately 90,000 and a protein with M(r) approximately 200,000 were found to be degraded. Structurally, this was accompanied by the disintegration of the vimentin filament network and the disappearance of the microfilament network. In contrast to our in vivo observations (Honer et al., 1991), prominent stress fibers and chromatin structure seemed to be rather resistant to the action of this protease. PMID- 1516139 TI - Transforming growth factor-beta-like activity is secreted by rabbit renal cortical tubular cells in primary culture. AB - The activity of an autocrine growth factor in a medium conditioned by cultured rabbit renal cortical tubular cells was investigated. Little stimulatory growth activity for tubular cells was observed in the conditioned medium, and inhibitory activity was seen only in acidified conditioned medium. This factor stimulated the colony formation of NRK 49F cells in soft agar only with epidermal growth factor and inhibited the DNA synthesis of primary cultured rat hepatocytes, and its molecular weight was about 25 kDa. The factor was neutralized by the specific antibody to transforming growth factor (TGF)-beta 1. These results indicate that renal tubular epithelial cells can produce latent TGF-beta in primary culture. PMID- 1516140 TI - Bioenergetics and cell communication; cell uncoupling seen as a protective mechanism in cardiac muscle. AB - Differences in rate of ATP resynthesis between apposing heart cells were created by dialysing 2-4-dinitrophenol (0.01-0.05 mM) into just one cell of isolated heart cell pairs. When 0.01 mM of dinitrophenol was used the junctional conductance (gj) remained unchanged for at least 8 min if cell 1 (normal) was pulsed at low rate (0.04 Hz). The increment in rate of pulsing to 4 Hz caused a fast decrease (13%) of gj within 30 sec. This change in gj was spontaneously reversed. With 0.05 mM of dinitrophenol cell uncoupling was produced if cell 1 (normal) was stimulated at 4 Hz for 25-30 sec. Despite the suppression of electrical coupling (which was not reversed within 8 min.) no contracture or signs of deterioration of the experimental conditions were found. Cell uncoupling can be seen as a protective mechanism providing opportunity to energy-depleted cells to re-establish their ATP stores. PMID- 1516141 TI - Influence of gonadotropin (FSH + LH) and thyrotropin (TSH) on the multiplication of Chinese hamster ovary (CHO) cells. Impact of the age of the culture. AB - CHO cells repeatedly treated with gonadotropin showed peak division rates after their third exposure and a decrease in the mitotic rate after their fourth exposure. Thyrotropin induced a considerable decrease in the mitotic rate following the first exposure, a significant increase after the second and a further decrease following the third and fourth exposures. The pattern did not differ between the two hormones when the cells were exposed further. The age (density of the cell cultures) had an appreciable influence on hormone-provoked changes in the mitotic rate, this differing only in intensity and never in the response following the initial re-exposure. PMID- 1516142 TI - Expression of Tetrahymena actin in mammalian cells. AB - We previously revealed that Tetrahymena actin can copolymerize with rabbit skeletal muscle actin whereas it has a very divergent primary structure and some unusual properties. To investigate the effects of coexistence of this unusual Tetrahymena actin in mammalian cells, we here transfected Tetrahymena actin gene on an expression vector into COS-1 cells. From the results of immunofluorescence microscopy, it was found that Tetrahymena actin expressed in COS-1 cells copolymerized with intrinsic actin, and it was conspicuously localized to the tips of microfilament core bundles in microspikes. On the other hand, increase in cell number tended to cease temporarily about 24 hr after transfection with Tetrahymena actin gene, implying the inhibition of cytokinesis by Tetrahymena actin coexistence. PMID- 1516143 TI - Increased efficiency of gene transfection in primary cultures of adult rat hepatocytes stimulated to proliferate: a comparative study using the lipofection and the calcium phosphate precipitate methods. AB - Transfection of the beta-galactosidase gene in quiescent cultures of adult rat hepatocytes with the calcium phosphate precipitate or the lipofection methods gave a higher level of beta-galactosidase gene expression with the lipofection than with the calcium phosphate precipitate method, but the transfection efficiency was weak in both cases. Transfection of hepatocytes stimulated to proliferate before transfection either in vivo by partial hepatectomy or in vitro by epidermal growth factor was more efficient than transfection of quiescent hepatocytes, and the lipofection method gave better results than the calcium phosphate precipitate method. PMID- 1516144 TI - Cosedimentation of pea root polysomes with the cytoskeleton. AB - When conventional, high ionic strength buffers were used for the isolation of polysomes from pea roots, only about 10% were retained in the detergent-insoluble pellet, and they were not degraded by endogenous RNase. A low ionic strength, cytoskeleton-stabilizing buffer increased retention to 60%, but polysomes were severely degraded. The RNase inhibitors, ribonucleoside-vanadyl complexes, heparin, KCl and ammonium sulphate lessened degradation but caused release, while Tris-HCl at 15-25 mM was able to prevent degradation without causing release. Cosedimentation of polysomes with the cytoskeleton is not an artefact of adsorption or trapping since isolated polysomes labelled through their nascent polypeptides and added to unfractionated tissue were not retained in the cytoskeletal pellet. PMID- 1516145 TI - Stage-specific mouse testis cell surface alterations detected by fluorescence labeled lectins. PMID- 1516146 TI - Cytoskeleton of liver perisinusoidal cells (lipocytes) in normal and pathological conditions. PMID- 1516147 TI - Microtubule oscillations. PMID- 1516148 TI - Association of the beta isoform of protein kinase C with vimentin filaments. AB - Protein kinase C (PKC) isoforms are key mediators in hormone, growth factor, and neurotransmitter triggered pathways of cell activation (Nishizuka: Science 233:305-312, 1986; Nature 334:661-665, 1988). Stimulation of kinase activity by diacylglycerol and calcium often leads to translocation of PKC from the cytosol to a particulate fraction (Kraft and Anderson: Nature 301:621-623, 1983). The beta isoform of PKC is translocated and degraded much more rapidly than the alpha isoform in phorbolester-stimulated rat basophilic leukemia (RBL) cells (Huang et al.: J. Biol. Chem. 264:4238-4243, 1989). We report here immunofluorescence evidence that the distributions of PKC alpha and beta are strikingly different in antigen-activated RBL cells. PKC beta associates with perinuclear filaments and filaments that extend from the perinuclear area to the cell periphery whereas PKC alpha concentrates in regions of the cell periphery. This distribution of PKC beta is distinctly different from that of actin filaments and microtubules as determined by phalloidin staining and by anti-tubulin antibody labeling. In contrast, the staining patterns obtained with antibodies to PKC beta and to the intermediate filament protein vimentin are almost identical, indicating that PKC beta associates with vimentin filaments. These bundles of 100 A filaments may provide docking sites for interactions of PKC beta with its substrates and thus confer specificity to the actions of this isoform. PMID- 1516149 TI - Actin-binding proteins regulate the work performed by myosin II motors on single actin filaments. AB - Regulation of actin/myosin II force generation by calcium [Kamm and Stull, Annu. Rev. Physiol. 51:299-313, 1989] and phosphorylation of myosin II light chains [Sellers and Adelstein, "The Enzymes," Vol. 18, Orlando, FL: Academic Pres, 1987, pp. 381-418] is well established. However, additional regulation of actin/myosin II force generation/contraction may result from actin-binding proteins [Stossel et al., Ann. Rev. Cell Biol. 1:353-402, 1985; Pollard and Cooper, Ann. Rev. Biochem. 55:987-1035, 1986] as they affect the gel state of the actin cytomatrix [reviewed in Taylor and Condeelis, Int. Rev. Cytol., 56:57-143, 1979]. Regulation of the gel state of actin may determine whether an isotonic or isometric contraction results from the interaction between myosin and actin. We have extended the single actin filament motility assay of Kron and Spudich [Proc. Natl. Acad. Sci. U.S.A. 83:6272-6276, 1986] by including filamin or alpha-actinin on the substrate with myosin II to examine how actin-crosslinking proteins regulate the movements of single actin filaments. Increasing amounts of actin crosslinking proteins inhibit filament velocity and decrease the number of filaments moving. Reversal of crosslinking yields increased velocities and numbers of moving filaments. These results support the solation-contraction coupling hypothesis [see Taylor and Fechheimer, Phil. Trans. Soc. London B 299:185-197, 1982] which proposes that increased crosslinking of actin inhibits myosin-based contraction. This study also illustrates the potentially varied roles of different actin-crosslinking proteins and offers a novel method to examine actin-binding protein activity and their regulation of motility at the single molecule level. PMID- 1516150 TI - Role of cytochrome P-450IIE1 in N-nitroso-N-methylaniline induced hepatocyte cytotoxicity. AB - 1. The cytotoxicity of N-nitrosomethylaniline (NMA) towards hepatocytes isolated from rats was prevented by acetone or ethanol (inhibitors for cytochrome P 450IIE1) but not by metyrapone or SKF525A (inhibitors for cytochrome P 450IIB1/2). Various alcohols, secondary ketones and isothiocyanates that induced cytochrome P-450IIE1 were also found to be protective. Various aromatic and chlorinated hydrocarbon solvents that are substrates or inducers of cytochrome P 450IIE1 also prevented NMA cytotoxicity. Nitrogen-containing heterocycles that induced cytochrome P-450IIE1 were less effective. Further evidence that cytochrome P-450IIE1 was responsible for the activation of NMA was the marked increase in hepatocyte susceptibility if hepatocytes from pyrazole-induced rats were used. 2. NMA was more cytotoxic to hepatocytes isolated from phenobarbital pretreated rats than uninduced rats. However, metyrapone now prevented and SKF525A delayed the cytotoxicity whereas ethanol, acetone, allyl isocyanate, isoniazid or trichloroethylene had no effect on the susceptibility of phenobarbital-induced hepatocytes. Furthermore, microsomes isolated from phenobarbital-pretreated rats had higher NMA-N-demethylase activity which was more inhibited by metyrapone and SKF525A than that of uninduced microsomal activity. By contrast the N-demethylase activity of phenobarbital induced microsomes was more resistant to acetone, ethanol, hexanal, trichloroethylene and toluene than uninduced microsome. 3. The above results suggest that cytochrome P 450IIE1 catalyses the cytotoxic activation of NMA in normal or pyrazole-induced hepatocytes whereas cytochrome P-450IIB1/2 is responsible for cytotoxicity in phenobarbital-induced hepatocytes. PMID- 1516151 TI - Organ-selective induction of cytochrome P-450-dependent activities by indole-3 carbinol-derived products: influence on covalent binding of benzo[a]pyrene to hepatic and pulmonary DNA in the rat. AB - Indole-3-carbinol (I3C) is a dietary modulator of carcinogenesis that can reduce the level of carcinogen binding to DNA. I3C-derived products are potent inducers of certain cytochrome P-450(CYP)-dependent enzyme activities. To investigate whether the protective effects of I3C against carcinogen damage to DNA are associated with increased activities of CYP1A1 enzymes, we examined the relationship of I3C-mediated organ-specific CYP enzyme induction with total levels of benzo[a]pyrene (BP) binding to hepatic and pulmonary DNA of rats. Oral intubation (PO) of I3C (500 mumol/kg body wt.) in 10% DMSO in corn oil produced after 20 h, increases in ethoxyresorufin O-deethylase (EROD) activities (associated with CYP1A1 isozyme) of 700-fold, 245-fold and 36-fold in small intestine, lungs and liver, respectively, compared with activities in untreated controls. Hepatic aryl hydrocarbon hydroxylase (AHH) activity was increased 4 fold under these conditions. Pentoxyresorufin O-depentylase (PROD) activity (associated with CYP2B isoenzyme) was increased 6-fold in the liver but was unaffected in lung and small intestine. Intraperitoneal injection (IP) of I3C (500 mumol/kg body wt.) produced no significant change in EROD or PROD activities in lung, liver, or small intestine. PO administration of the acid reaction mixture (RXM) of I3C increased hepatic AHH activity (5-fold) and EROD activities in small intestine (650-fold), lung (100-fold) and liver (18-fold). IP administration of RXM (equivalent to 500 mumol I3C/kg body wt.) significantly increased only EROD activity in lung and liver, but did not affect EROD activity in small intestine, AHH activity in liver, or PROD activity in any of the organs examined. Twenty hours after inducer treatment, half of the rats were treated PO with 0.2 mumol [3H]BP in corn oil. Analysis of tissues 5 h after BP administration indicated that compared with untreated controls, administration of I3C and RXM by either route reduced by 30-50% the level of BP binding to hepatic DNA, an effect that was not correlated to CYP1A1 enzyme induction in any of the organs examined. However, PO administration of I3C and RXM produced a 50-70% decrease in carcinogen binding to pulmonary DNA, while IP administration of inducers had no effect on DNA binding in this organ. These results with the lung are consistent with an increased presystemic clearance of BP in the intestine and are discussed in terms of the role of induction of intestinal CYP1A1 activity in the decreased lymphatic and venous transport of unmetabolized BP to the lung. PMID- 1516152 TI - Reactions of the Wurster's red radical cation with hemoglobin and glutathione during the cooxidation of N,N-dimethyl-p-phenylenediamine [correction of phenlenediamine] and oxyhemoglobin in human red cells. AB - N,N-Dimethyl-p-phenylenediamine (DMPD) reacted directly with oxyhemoglobin under formation of ferrihemoglobin and, presumably, the N,N-dimethyl-p-phenylenediamine radical cation (DMPP.+). The apparent second-order rate constant of this reaction was 1 M-1 s-1 (pH 7.4, 37 degrees C). The reaction rate was diminished by catalase (by 1/3) and by superoxide dismutase (by 1/5). The apparent second-order rate constant of ferrihemoglobin formation by DMPD.+ was 5 x 10(3) M-1 s-1. Since DMPD.+ is disproportionated by 50% at pH 7.4, the quinonediimine could not be excluded as the ultimate ferrihemoglobin forming oxidant. To prove this hypothesis, the disproportionation equilibrium was shifted to the radical side by addition of excess DMPD. Ferrihemoglobin formation was thereby increased, indication that the radical was the responsible oxidant. In contrast to ferrihemoglobin formation, reactions with glutathione occurred predominantly with the quinonediimine. The second-order rate constant of this reaction was 4 x 10(5) M-1 s-1 which approaches the value obtained with p-benzoquinone. In contrast to the corresponding reactions of the N,N,N',N'-tetramethyl-p-phenylenediamine radical cation, the disporportionation reaction of DMPD.+ was very fast, k = 2 x 10(6) M-1 s-1. Formation of glutathione disulfide was negligible and the main reaction products were two isomeric glutathione adducts, 2- and 3-(glutathione-S yl)-N,N-dimethyl-p-phenylenediamine. In human erythrocytes, DMPD produced many equivalents of ferrihemoglobin, diminished glutathione and produced both thioethers. In contrast to ferrihemoglobin formation, DMPD and glutathione disappearance as well as thioether appearance occured only after a marked lag phase. The calculated steady state concentration of DMPD.+ was only 4 x 10(-6) the DMPD concentration, as long as ferrihemoglobin was low. At increasing ferrihemoglobin higher steady state concentrations of the radical are attained. In fact, preformed ferrihemoglobin in red cells significantly accelerated DMPD and glutathione disappearance. This effect was completely prevented in the presence of ferrihemoglobin-complexing cyanide. The presented experiments once more appoint blood as a metabolically competent organ for the biotransformation of aromatic amines. PMID- 1516153 TI - Rat carotid neointimal smooth muscle cells reexpress a developmentally regulated mRNA phenotype during repair of arterial injury. AB - Smooth muscle cells (SMCs) cultured from the neointima of injured rat carotid arteries have a different shape and organization in vitro than SMCs from the uninjured media. The morphology of neointimal SMCs from adult rats strongly resembles that of a subset of medial SMCs from 12-day-old rat pups. In the present study, we show that adult carotid neointimal SMCs in vitro express the platelet-derived growth factor (PDGF)-B gene but have little or no PDGF alpha receptor mRNA. In contrast, medial SMCs from contralateral uninjured carotids, grown and passaged under identical conditions, contain abundant PDGF alpha receptor mRNA but little or no PDGF-B mRNA. Transcript levels for PDGF-A or PDGF beta-receptor were not different in neointimal versus medial SMC cultures. The PDGF mRNA phenotype of adult neointimal SMCs strongly resembles that of an aortic medial SMC subset from newborn rat pups. Although intriguing, the differences in SMC phenotypes we observed in cell culture may depend on unique conditions in vitro and do not necessarily mean that analogous SMC diversity also exists in vivo. To address this question, we constructed and screened a SMC cDNA library for additional molecular markers of the common "pup-intimal" SMC phenotype. Two cDNA clones were identified whose cognate mRNA levels were developmentally regulated in rat aorta in vivo and were present at high levels in the adult carotid neointima formed 2 weeks after balloon catheter injury. Importantly, elevated levels of these two cognate mRNAs in carotid neointima compared with underlying media were maintained in cultures of neointimal versus medial SMCs in vitro. DNA sequence analysis indicated that the cDNA clones encoded rat tropoelastin and alpha 1 procollagen (type I). These results provide further evidence that neointima formation in the adult rat carotid artery depends on reexpression of an SMC phenotype or subpopulation with special properties characteristic of earlier stages of artery wall development. Our studies to date indicate that two of these special properties are paracrine growth factor production and extracellular matrix synthesis. PMID- 1516154 TI - Epicardial coronary artery responses to acetylcholine are impaired in hypertensive patients. AB - Hypertension is a risk factor for coronary atherosclerosis possibly via an adverse effect on the vascular endothelium. Endothelium-mediated relaxation is impaired in animal models of hypertension. However, the effects of hypertension on human coronary artery endothelial cell function are unknown. To test whether endothelium-mediated relaxation is impaired in the coronary arteries of patients with hypertension, we studied 14 patients with essential hypertension requiring therapy and 15 nonhypertensive control patients undergoing cardiac catheterization. All had angiographically normal, smooth-appearing coronary arteries. Patients were matched for age and other coronary atherosclerosis risk factors. To assess endothelial cell function, the endothelium-dependent vasodilator acetylcholine (ACh, 0.01, 0.1, and 1.0 microM) and the endothelium independent vasodilator nitroglycerin (40 micrograms) were selectively infused into the left anterior descending or circumflex coronary artery. Diameter change (expressed as percent) was assessed using quantitative angiography. There was a marked vasoconstrictor response to serial doses of ACh in hypertensive patients ( 7%, -21%, and -27%) compared with control patients (-4%, -5%, and -7%) (p less than 0.02). The vasodilator response to nitroglycerin was preserved in hypertensive patients (+29%) and control patients (+25%) (p = NS), suggesting that endothelial cell dysfunction accounted for the differences in response to ACh. Thus, patients with hypertension have an accentuated coronary vasoconstrictor response to ACh, suggesting that endothelium-mediated regulation of coronary vascular tone is impaired by essential hypertension. This may reflect more generalized coronary endothelial changes contributing to the pathogenesis of atherosclerosis as well as hypertension. PMID- 1516155 TI - Effects of hypoxia on heparan sulfate in bovine aortic and pulmonary artery endothelial cells. AB - Newly synthesized heparan sulfates purified from the cell layer of bovine aortic endothelial cells (BAECs) and main pulmonary artery endothelial cells (BPAECs) cultured under either normoxic (21% oxygen) or hypoxic (3% oxygen) conditions were characterized by size, charge, and capacity to bind to antithrombin III. Incorporation of radiolabeled sulfate into cell layer-associated heparan sulfate was reduced by 70% in BAECs and by 45% in BPAECs during exposure to 3% oxygen; degradation of radiolabeled heparan sulfate was not affected by hypoxia. However, the percentage of total radiolabeled heparan sulfate that bound to antithrombin III was increased by 33% for BAECs and by 120% for BPAECs when compared with radiolabeled heparan sulfate synthesized during the 21% oxygen exposure. Both the high- and low-antithrombin III affinity radiolabeled heparan sulfate consisted of two components of different sizes; the low-affinity components (mean sizes, 60 and 40 kd) generated under normoxic conditions were smaller than their respective high-affinity components (mean sizes, 70 and 55 kd) by molecular sieve chromatography. The components of low-antithrombin III affinity heparan sulfate generated during exposure to 3% oxygen were increased in size compared with the corresponding low-affinity components generated during the 21% oxygen exposure for both BPAECs and BAECs. In addition, the amount of the larger high antithrombin III affinity component was reduced in both cell types exposed to hypoxia. There was no difference in functional heparin-like activity per dish between cells cultured at 3% and 21% oxygen; BAECs had twofold to threefold greater activity per dish than did BPAECs at both levels of oxygen.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1516156 TI - Role of endothelium-derived prostaglandins in hypoxia-elicited arteriolar dilation in rat skeletal muscle. AB - The aims of the present study were to determine the response of rat cremaster muscle first-order arterioles to hypoxia and the role of endothelium-derived prostaglandins in the response. Isolated arterioles were cannulated, pressurized to 65 mm Hg, and studied in a no-flow condition in a bath containing Krebs' bicarbonate solution, pH 7.4, equilibrated with 21% O2-5% CO2-74% N2 (PO2, 150 mm Hg) or 95% N2-5% CO2 (PO2, 15 mm Hg [hypoxia]). Responses to hypoxia and vasoactive substances were studied before and after removal of the endothelium or blockade of prostaglandin synthesis by the administration of indomethacin (10(-5) M). Addition to the suffusion solution of arachidonic acid (10(-7) and 10(-6) M), prostaglandin E2 (10(-9) and 10(-8) M), acetylcholine (10(-8) and 10(-6) M), or sodium nitroprusside (10(-8) M) evoked significant arteriolar dilation. When the bath PO2 was reduced from 150 to 15 mm Hg, arteriolar diameters increased by 58.8 +/- 9.3 microns (61%). Removal of the endothelium completely inhibited responses to hypoxia, acetylcholine, and arachidonic acid, whereas responses to sodium nitroprusside and prostaglandin E2 remained unaltered. In arterioles with an intact endothelium, indomethacin completely inhibited the responses to hypoxia and arachidonic acid, whereas responses to acetylcholine and sodium nitroprusside were unaltered. These findings support the conclusion that endothelium-derived prostaglandins mediate the arteriolar dilation to hypoxia in rat skeletal muscle arterioles. PMID- 1516157 TI - Effects of 2,4-dinitrophenol or low [ATP]i on cell excitability and action potential propagation in guinea pig ventricular myocytes. AB - Inhibition of aerobic metabolism leads to a major disruption of cardiac cell homeostasis. The purpose of the present study was twofold: 1) We determined the relative importance of junctional and nonjunctional membrane resistance (Rj and Rm, respectively) in the development of propagation failure during inhibition of aerobic metabolism in guinea pig ventricular cell pairs. 2) We used the patch action potential clamp technique in single ventricular myocytes to study some of the properties of the membrane channels that are responsible for shortening of action potential duration and eventual failure of cell excitation after metabolic blockade. In most experiments, whole-cell patch pipettes were filled with a solution containing 1 mM EGTA, 5 mM HEPES, and 5 mM ATP. Our results in cell pairs showed that pharmacological inhibition of aerobic metabolism with the mitochondrial uncoupler 2,4-dinitrophenol (DNP) led to a drop in Rm followed by an increase in Rj. The increase in Rj was not sufficient to cause a measurable delay in cell-to-cell propagation, whereas the drop in Rm consistently led to failure of cell excitation. Similar results were obtained in additional experiments in which the EGTA concentration in the pipette was reduced to 50 microM. Similar results were also obtained by loading the recording patch pipettes with a solution containing only 0.1 mM ATP. Our patch-action potential clamp experiments, on the other hand, revealed that DNP induced the opening of time- and voltage-independent membrane channels, with a unitary conductance of 23 pS. The channels allowed for the passage of outward current in the voltage range of the action potential, and the increase in membrane patch conductance correlated with the observed shortening of action potential duration during DNP superfusion. Our experiments provide the first simultaneous recordings of action potentials and DNP-induced channel currents in guinea pig ventricular myocytes. Overall, the data provide new evidence for the understanding of the cellular and subcellular mechanisms involved in the development of slow conduction velocity and propagation block after metabolic blockade. PMID- 1516158 TI - Effects of fibrous cap thickness on peak circumferential stress in model atherosclerotic vessels. AB - It is likely that factors other than stenosis severity predispose some atherosclerotic plaques to rupture. Because focal increases in circumferential stress may be an important mechanism of plaque rupture, we examined peak circumferential stress of atherosclerotic lesions by using finite element analysis based on idealized two-dimensional cross sections of diseased vessels similar to intravascular ultrasound images. The study was designed to test the hypothesis that subintimal plaque structural features such as thickness of the fibrous cap are more important factors in the distribution of stress in the plaque than stenosis severity. The analysis incorporated equilibrium biomechanical parameters from normal and diseased vessels and determined the stress distribution within the plaque at a mean luminal internal pressure of 110 mm Hg. With a constant luminal area reduction of 70%, maximum circumferential stress (sigma max) normalized to luminal pressure (sigma max/P) increased from 6.0 to 24.8 as the thickness of the lipid pool was increased from 38% to 54% of the plaque thickness because of the thinner fibrous cap over the lipid pool. When the lipid pool thickness was constant, increasing the stenosis severity from 70% to 91% by increasing the fibrous cap thickness decreased sigma max/P from 24.8 to 4.7. When no lipid pool was present and the stenosis severity was increased from 70% to 99%, sigma max/P decreased from 5.3 to 4.7. Thus, reducing the fibrous cap thickness dramatically increases peak circumferential stress in the plaque, whereas increasing the stenosis severity actually decreases peak stress in the plaque.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1516159 TI - Effects on the rabbit coronary artery of LP-805, a new type of releaser of endothelium-derived relaxing factor and a K+ channel opener. AB - In the rabbit epicardial coronary artery, 8-tert-butyl-6,7-dihydropyrolo[3,2-e]5 methylpyrazolo [1,5-a]pyrimidine-3-carbonitrile (LP-805, greater than 0.1 microM) hyperpolarized the muscle membrane in both proximal (diameter, 1-1.2 mm) and distal (diameter, 0.1-0.2 mm) regions of intact (+E) tissue, in which endothelium is present, and endothelium-denuded (-E) tissue. LP-805-induced hyperpolarization was inhibited by glibenclamide. In -E tissues in both regions, acetylcholine (ACh, greater than 0.1 microM) depolarized the membrane, and LP-805 inhibited the depolarization. However, in +E tissues, ACh (greater than 0.1 microM) transiently hyperpolarized the membrane that was not modified by glibenclamide (10 microM), charybdotoxin (100 nM), and NG-nitro-L-arginine (L-NNA, 100 microM). In -E tissues of both regions, LP-805 consistently inhibited the 10 microM ACh-induced contraction (IC50, 2.8 microM), and 10 microM glibenclamide shifted this concentration-response curve to the right (IC50, 20 microM). In +E tissues, LP 805 more potently inhibited the ACh-induced contraction (IC50, 0.3 microM), and this inhibition was prevented by L-NNA (100 microM) but not by indomethacin or glibenclamide (10 microM). In -E and +E tissues of both regions, LP-805 repolarized the high K(+)-induced depolarization (less than 20 mM) and relaxed the tissues precontracted by high K+ (less than 30 mM); these electrical and mechanical effects of LP-805 were prevented by glibenclamide (10 microM) in +E tissues. In +E tissues, the K(+)-induced contraction (less than 30 mM) was more strongly inhibited than in -E tissues, but after treatment with L-NNA, LP-805 relaxed -E and +E tissues precontracted to the same extent in the presence of high K+. LP-805 (10 microM) did not inhibit the Ca(2+)-induced contraction in skinned muscle tissues but did slightly inhibit the ACh-induced contraction in Ca(2+)-free solution containing 2 mM EGTA. Thus, LP-805 has a potent releasing action on endothelium-derived relaxing factor and also the potential to open the glibenclamide-sensitive K+ channel. These events would account for the dilation of the rabbit coronary artery exposed to LP-805. PMID- 1516160 TI - Different effects of alpha- and beta-adrenergic stimulation on cytosolic pH and myofilament responsiveness to Ca2+ in cardiac myocytes. AB - alpha-Adrenergic stimulation (alpha-AS) and beta-adrenergic stimulation (beta-AS) of the myocardium are associated respectively with an increase and a decrease in myofilament responsiveness to Ca2+. We hypothesized that changes in cytosolic pH (pH(i)) may modulate these opposite actions of alpha-AS and beta-AS. The effects of alpha-AS (50 microM phenylephrine and 1 microM nadolol) and beta-AS (0.05 microM isoproterenol) on contraction and either cytosolic Ca2+ (Cai) or pH(i) were assessed in adult rat ventricular myocytes bathed in bicarbonate buffer (pH 7.36 +/- 0.05). In cells loaded with the ester derivative (AM form) of indo-1, the 410/490-nm ratio of emitted fluorescence indexed Cai. Myofilament responsiveness to Ca2+ was assessed by the relaxation phase of the length-indo-1 fluorescence relation during a twitch. alpha-AS and beta-AS shifted this relation in opposite directions, indicating that alpha-AS increased and beta-AS decreased myofilament responsiveness to Ca2+. In addition, the positive inotropic action of alpha-AS was associated with an increased Cai transient amplitude in 50% of the myocytes (n = 12), whereas beta-AS always increased Cai (n = 5). In cells loaded with the fluorescent pH(i) probe SNARF-1 AM, the emitted 590/640-nm fluorescence is a measure of pH(i). The effect of alpha-AS on the extent of cell shortening during the twitch (ES) was expressed as the percentage of resting cell length. Both ES and pH(i) were assessed in myocytes bathed in 1.5 mM [Ca2+] and stimulated at 0.5 Hz (control ES, 7.4 +/- 1.5%; control pH(i), 7.11 +/- 0.05; n = 10). alpha-AS enhanced both ES (delta ES, 1.8 +/- 0.6%; p less than 0.05) and pH(i) (delta pH(i), 0.06 +/- 0.01; p less than 0.005), and there was a significant correlation between delta ES and delta pH(i) (r = 0.76, p less than 0.05). A similar effect of alpha-AS on pH(i) was observed in the absence of electrical stimulation (n = 8). The alpha-AS-induced enhancement of ES and pH(i) was abolished by 10 microM ethylisopropylamiloride, a Na(+)-H+ exchange inhibitor (n = 7). In additional experiments, myocytes were preincubated either with 0.2 microM 4 beta-phorbol 12-myristate 13-acetate (n = 8) or with 5 nM staurosporine (n = 8), which have been shown to downregulate and inhibit Ca(2+)-activated phospholipid-dependent protein kinase C, respectively. In either group, alpha-AS had no effect on pH(i) and decreased ES to approximately 60% of control.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1516161 TI - Measurement of endothelial permeability to 125I-low density lipoproteins in rabbit arteries by use of en face preparations. AB - A procedure of en face quantitative autoradiography of the endothelium (Hautchen preparations) was developed to examine regional variations in 125I-low density lipoprotein (125I-LDL) permeability in the arterial wall in vivo. Endothelial preparations from fixed arterial tissue and calibration standards consisting of known concentrations of 125I-albumin were dipped in nuclear emulsion, exposed for 1-3 months, developed, and stained with hematoxylin. Digital image analysis was used to analyze dark-field images of autoradiographs. Background grain densities on cold endothelial preparations were 30-100% higher than on glass, but the variability in grain densities on the two different surfaces was similar. Regression slopes of grain density versus concentration for calibration standards were the same for sections placed on cold tissue or glass. For 1-5-microns-thick calibration standards of the same concentration, the grain density was proportional to the total amount of radioactivity per unit area. The results indicated that errors arising from nonuniformities in preparation thickness were minimal, and permeabilities and intimal concentrations could be determined. Rabbits were killed 10 minutes after injection of 125I-LDL, and endothelial preparations were made. For regions of uniformly low grain density in the rabbit aorta, the 125I-LDL permeability was 1.9 +/- 0.8 x 10(-8) cm/sec, and the effective diffusion coefficient was 5.4 +/- 3.1 x 10(-10) cm2/sec. Errors in the estimated permeability arising from nonuniformities in tissue thickness were the same as the reported experimental variability. Analysis of elevated regions of permeability suggested that 125I-LDL was binding to the extracellular matrix. Approximately 25% of the sites of elevated grain density were associated with mitotic endothelial cells, and such regions had higher permeabilities than sites associated with nonmitotic cells. Around intercostal arteries, sites of highest permeability were distal and lateral to the vessels and occurred where lesions first develop in hypercholesterolemic rabbits. PMID- 1516162 TI - Sequence of excitation as a factor in sympathetic-parasympathetic interactions in the heart. AB - We determined the influence of differences in the time of initiation of sympathetic and vagal stimulation (both at 10 Hz) on the cardiac autonomic interactions in 16 open-chest anesthetized dogs. We always ended the concurrent sympathetic and vagal stimulations simultaneously. Sympathetic stimulation alone for 1 minute increased heart rate by 90 +/- 7 (mean +/- SEM) beats per minute, and vagal stimulation alone for 1 minute decreased heart rate by 67 +/- 5 beats per minute; i.e., the algebraic sum of these responses was an increase of 23 beats per minute. However, combined sympathetic and vagal stimulation for 1 minute actually decreased heart rate by 35 beats per minute; i.e., the vagal effects predominated. When vagal stimulation was initiated first, the chronotropic responses to combined stimulation were not significantly affected by the duration of antecedent vagal stimulation. However, when sympathetic stimulation was initiated first, the vagal predominance (disparity between the summated individual responses and the combined response) progressively diminished as we increased the duration of antecedent sympathetic stimulation. The vagal predominance diminished from a value of 67 +/- 21 beats per minute when the stimulations were initiated simultaneously to a value of 37 +/- 21 beats per minute when the duration of antecedent sympathetic stimulation was 10 minutes. Sympathetic stimulation releases not only norepinephrine but also neuropeptide Y, and this neuropeptide inhibits vagal neurotransmission. Our data suggest, therefore, that the longer the antecedent sympathetic stimulation, the greater the inhibition of vagal neurotransmission (presumably by the neuropeptide Y) and, therefore, the less pronounced the vagal predominance. PMID- 1516163 TI - Microvascular sites and mechanisms responsible for reactive hyperemia in the coronary circulation of the beating canine heart. AB - Our aim was to elucidate the site and mechanism responsible for reactive hyperemia in coronary circulation. In in vivo beating canine hearts, microvessels of the left anterior descending coronary artery (LAD) were observed through a microscope equipped with a floating objective. Flow velocity of the LAD was measured with a suction-type Doppler probe. The LAD was occluded for 20 or 30 seconds and then released, and reactive hyperemia was observed before and after 8 phenyltheophylline (7.5 mg/kg i.v.) or glibenclamide (200 micrograms/kg into the LAD) infusion. During the occlusion, only arterial microvessels smaller than 100 microns in diameter dilated. Dilation of those vessels was partially attenuated by 8-phenyltheophylline and completely abolished with glibenclamide. In the early phase of reactive hyperemia, all arterial microvessels dilated, and the magnitude of peak dilation was greater in vessels smaller than 100 microns compared with those larger than 100 microns. Vasodilation during reactive hyperemia ceased within 60 seconds in vessels smaller than 100 microns but was sustained for more than 120 seconds in those larger than 100 microns. 8-Phenyltheophylline did not change peak dilation of arterial microvessels but reduced dilation after the peak. Glibenclamide remarkably attenuated dilation of all arterial microvessels in the whole phase of reactive hyperemia. These results indicate that all arterial microvessels are responsible for reactive hyperemia after coronary artery occlusions of 20-30 seconds, but there is greater participation of vessels smaller than 100 microns in the early phase of reactive hyperemia. Dilation of vessels larger than 100 microns assumes an important role in the later phase. ATP sensitive K+ channels mediate dilation of arterial microvessels both in brief ischemia and reactive hyperemia. PMID- 1516164 TI - Albumin transport characteristics of rat aorta in early phase of hypertension. AB - The effects of early-stage hypertension on the macromolecular transport characteristics of the aorta have been investigated in rats 1 week after the ligature of the abdominal aorta between the two renal arteries. The animals were left untreated or treated for 1 week with an angiotensin converting enzyme inhibitor (enalapril, 6 mg/kg per day). Blood pressure of a subgroup of hypertensive rats was acutely lowered to a normal level by injection of enalaprilat (1.5 mg/kg) at the time of the experiment. 131I-Albumin and 125I albumin were injected 90 minutes and 5 minutes, respectively, before the rats were killed. The transmural distribution of the relative tissue concentrations across the wall was obtained using a serial frozen-section technique. Short-term albumin uptake permitted calculation of apparent endothelial permeability coefficients, and 90-minute uptake was used to estimate the steady-state albumin distribution within the media. The effect of early-stage hypertension on the characteristics of the arterial macromolecular transport depended on the aortic site; the ascending aortic arch appeared not to be affected. In the thoracic and abdominal aorta, the endothelial permeability coefficients increased significantly in hypertensive rats. This increase was not a direct effect of the arterial pressure, since the values were not significantly different when the pressure was acutely normalized. The 90-minute albumin concentration in the media was enhanced in hypertensive rats and returned to the normal value by acutely lowering the blood pressure, indicating that the increase observed in hypertensive rats resulted from a direct effect of pressure, possibly increased pressure-driven convection and/or pressure-induced stretching of the wall. Treatment by angiotensin converting enzyme inhibitor prevented hypertension and protected against its effects in hypertensive animals. PMID- 1516165 TI - Endothelial modulation of the ouabain-induced contraction in human placental vessels. AB - Ouabain (1 x 10(-7)-3 x 10(-5) M) elicited concentration-dependent vasoconstriction in human placental arteries and veins. These responses, but not those produced by 10(-6) M 5-hydroxytryptamine, were increased after the removal of vascular endothelium. In placental arteries, the respective blockade of cyclooxygenase or lipoxygenase with indomethacin of 5,8,11,15-eicosatetraynoic acid as well as the inactivation of nitric oxide with phenidone or oxyhemoglobin and the inhibition of nitric oxide synthesis with NG-monomethyl L-arginine (all at 10(-5) M) did not mimic the effects of endothelial denudation on ouabain evoked contractions. Bioassay experiments suggested that the above-mentioned endothelial effects are mediated by diffusible factors. 86Rb+ uptake, a method to measure sodium pump activity, was significantly reduced by the removal of endothelium. These results suggest the existence of an inhibitory modulation by the endothelium of the contractions induced by ouabain, likely mediated by a diffusible factor(s) released from these cells. The nature of this substance is unknown but is not related to prostaglandins or leukotrienes, and neither is it a nitric oxide-related compound. Its mechanism of action could be stimulating the activity of vascular sodium pump and/or antagonizing its inhibition by ouabain. PMID- 1516166 TI - Effect of brief myocardial ischemia on sympathetic coronary vasoconstriction. AB - The purpose of the present study was to determine whether sympathetic coronary vasoconstrictor responses are altered after brief ischemia and reperfusion. Adult mongrel dogs were anesthetized and instrumented for measurements of heart rate, arterial pressure, left ventricular pressure, left ventricular dP/dt, anterior myocardial wall thickening, and left circumflex coronary artery (LCX) and left anterior descending coronary artery (LAD) blood flow velocities. Changes in coronary vascular resistance were recorded during intravenous bolus doses of norepinephrine and bilateral electrical stimulation of the stellate ganglia. After beta-adrenergic blockade and bilateral vagotomy, electrical stimulation of the stellate ganglia increased coronary vascular resistance in the LAD and LCX beds by 38 +/- 5% and 39 +/- 5%, respectively. After a 15-minute LAD occlusion, repeat electrical stimulation produced increases in coronary resistance of 16 +/- 3% and 45 +/- 8%, respectively (p less than 0.05 for the LAD before versus after the occlusion). The peak increase in coronary vascular resistance to two doses of norepinephrine was unchanged. After a shorter period of myocardial ischemia (7 minutes), similar increase in coronary resistance to stellate stimulation were observed before (27 +/- 4%) and after (26 +/- 6%) myocardial ischemia. The mechanism of this impaired sympathetic coronary vasoconstriction was further tested by examining the responses to bretylium and tyramine. Brief ischemia did not alter the coronary constrictor responses to either bretylium or tyramine, suggesting that mechanisms governing prejunctional release of norepinephrine are intact in the postischemic coronary arterial bed.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1516167 TI - Depression of cardiac sarcolemmal phospholipase D activity by oxidant-induced thiol modification. AB - Myocardial phospholipase D (PLD) is primarily localized at the sarcolemmal level and selectively hydrolyzes phosphatidylcholine to form phosphatidic acid as part of the signal transduction mechanisms for regulating Ca2+ movements in the heart. Since the myocardial cell damage induced by oxidative stress is associated with abnormalities in Ca2+ homeostasis and thiol status, we examined the thiol group dependence and the effects of oxidant species on this enzyme. Sarcolemmal membranes isolated from rat heart were exposed to several types of thiol group modifiers. Alkylation with N-ethylmaleimide or methyl methanethiosulfonate, mercaptide formation with p-chloromercuriphenylsulfonic acid, and thiol-disulfide exchange with 5,5'-dithio-bis(2-nitrobenzoate) depressed sarcolemmal PLD activity; in all cases the depression was prevented by dithiothreitol. At different concentrations of N-ethylmaleimide the PLD depression correlated well (r = 0.98) with the decrease in total thiol group content of the membrane. The enzyme activity was not affected by xanthine-xanthine oxidase, a superoxide anion generating system, but was depressed by hydrogen peroxide (H2O2) in a concentration-dependent manner. This inhibitory effect was prevented by catalase as well as by dithiothreitol, but not by D-mannitol. The effect of a hydroxyl radical-generating system (Fenton reaction) could not be assessed because of an interfering direct inhibition by Fe2+. Dithiothreitol was also able to restore PLD activity in H2O2-pretreated membranes and to prevent a severe deactivation of the enzyme by hypochlorous acid (HOCI). Protection by glutathione and inhibition by its oxidized form were also observed.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1516168 TI - Blockade of beta 1-integrins in skin causes edema through lowering of interstitial fluid pressure. AB - The increased capillary fluid filtration required to rapidly create edema in acute inflammation can be generated by increased negativity of the interstitial fluid pressure (Pif). This observation suggests that connective tissues can "actively" enhance capillary fluid filtration. We now show that in vivo blockade of beta 1-integrin adhesion receptors in rat skin causes local edema concomitant with increased negativity of Pif. Experiments were performed on the dorsal side of the hind paw, and Pif was measured with sharpened glass capillaries (tip diameter, 3-7 microns) connected to a servo-controlled counterpressure system. Measurements were made after circulatory arrest had been induced with intracardiac potassium chloride in pentobarbital anesthesia. This procedure prevents the vascular phenomena of increased fluid and protein flux leading to edema formation, which in turn can increase Pif and therefore potentially mask an increased negativity of Pif. Control Pif averaged -0.58 +/- 0.81 (mean +/- SD) mm Hg (n = 37). Subdermal injection of 5 microliters monospecific rabbit anti-rat integrin beta 1-subunit immunoglobulin G caused increased negativity of Pif to average values between -4 and -6 mm Hg within 10 minutes after injection. Subdermal injection of 0.9% NaCl, preimmune immunoglobulin G, rat anti fibronectin, and peptides with Arg-Gly-Asp and Arg-Gly-Glu sequences did not change Pif significantly. In another series of experiments, 5 microliters anti beta 1 integrin immunoglobulin G was injected subdermally in rats with intact circulation and resulted in an increase in total tissue water corresponding to a doubling of the interstitial fluid volume in 10 minutes (p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1516169 TI - Effects of cycling and rigor crossbridges on the conformation of cardiac troponin C. AB - The results of work by several investigators indicate that crossbridge attachment serves as a positive feedback mechanism that transiently increases the Ca2+ affinity of troponin C (TnC) during each normal heartbeat. To monitor structural changes in the cardiac isoform of TnC (cTnC) associated with Ca2+ binding and crossbridge attachment in muscle, we labeled cTnC with the sulfhydryl-specific fluorescent probe 2-(4'-iodoacetamidoanilino)naphthalene-6-sulfonic acid (IAANS). When IAANS-labeled cTnC (cTnCIAANS) was substituted for endogenous TnC, the fluorescence intensity of cardiac and skeletal muscle preparations increased substantially during rigor crossbridge attachment in the absence of Ca2+ (pCa 9.2). In cardiac muscle, the fluorescence signal increased the same amount in rigor and maximal activation, whereas in skeletal muscle, it was higher in rigor (rigor: cardiac and skeletal = 1; pCa 4.0: cardiac = 0.98 +/- 0.13, skeletal = 0.59 +/- 0.05). This indicates that crossbridge attachment alone is capable of influencing the structure of cTnCIAANS. Because the relative fluorescence intensity of cTnCIAANS was more sensitive to Ca2+ than was force in both preparations (cardiac: pCa50 fluorescence = 6.05 +/- 0.05, pCa50 force = 5.51 +/- 0.11; skeletal: pCa50 fluorescence = 5.94 +/- 0.13, pCa50 force = 5.65 +/- 0.14), we measured the Ca2+ sensitivity of the strong crossbridge attachment (sinusoidal stiffness was measured by imposing 1 kHz at 0.1-0.2% muscle length) in rat trabeculae.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1516170 TI - Quantification of regional myocardial blood flow using 13N-ammonia and reoriented dynamic positron emission tomographic imaging. AB - BACKGROUND: Regional myocardial blood flow has been quantified using transaxial positron emission tomographic (PET) imaging and tracer kinetic modeling. However, the use of transaxial images limits the accuracy of regional partial volume corrections and the localization of the quantified regional flow values. The purpose of the present study was to overcome both problems by calculating regional flows from reoriented short-axis PET images. METHODS AND RESULTS: Twelve experiments were performed in four dogs. 13N-ammonia was injected intravenously while microspheres were administered into the left atrium during baseline, hyperemic, and low-flow conditions. Serial transaxial frames were acquired with a 15-plane PET scanner and reoriented into short-axis frames. The arterial input function and eight regional myocardial tissue activity curves were derived from the reoriented frames. The arterial input functions were corrected for ammonia metabolites, and the myocardial tissue curves were corrected for spillover of activity, partial volume effects, and heterogeneities in the image's spatial resolution introduced during reorientation. Corrections for regional partial volume were based on estimates of the regional myocardial activity thickness derived from reoriented diastolic images of the heart. The myocardial 13N-ammonia kinetics were described with a two-pool compartmental model. Values of regional myocardial blood flow by PET correlated linearly with those by microspheres (slope, 0.94; y intercept, 0.06 ml/min/g; r = 0.93) over a wide range of flows. CONCLUSIONS: Regional myocardial blood flow can be measured accurately and noninvasively from serially acquired and reoriented short-axis 13N-ammonia images, thus overcoming limitations inherent to the use of transaxially acquired images and permitting a more complete evaluation of regional blood flows throughout the left ventricular myocardium. PMID- 1516171 TI - Assessment of postreperfusion myocardial hemorrhage using proton NMR imaging at 1.5 T. AB - BACKGROUND: Intramyocardial hemorrhage occurs frequently after reperfusion of acute myocardial infarction. However, its significance has not yet been established, mainly because of the lack of methods for detecting such hemorrhage. The following ex vivo study was carried out to assess the potential of nuclear magnetic resonance (NMR) imaging to detect and quantitate postreperfusion intramyocardial hemorrhage. METHODS AND RESULTS: Sixteen adult mongrel dogs underwent 3 hours of coronary occlusion followed by 1 hour of reperfusion, and three dogs underwent 4 hours of occlusion without reperfusion. Radiolabeled microspheres and 51Cr-labeled red blood cells were used to assess flow and evaluate the extent of hemorrhage. These results were later compared with both NMR and histology. Spin-echo NMR imaging was performed on the excised hearts using a 1.5-T system. Macroscopic assessment of the sliced myocardium revealed the existence of hemorrhage in 14 of the 16 dogs that underwent reperfusion but in none of those with occlusion only. In all 16 dogs with reperfusion, zones of increased signal intensity (SI) ratio (1.68 +/- 0.41 compared with control, p less than 0.05) were seen in regions relating to the distribution of the occluded coronary artery, whereas in 13 of the 16 dogs, areas of decreased SI within the zone of increased SI ratio (0.81 +/- 0.16 compared with control, p less than 0.05) were also seen, corresponding to regions with macroscopic hemorrhage. In contrast, in the three dogs without reperfusion, no macroscopic hemorrhage was observed, and likewise, no NMR zones of reduced SI were detected. Hemorrhage size by NMR (decreased SI zones), correlated well with hemorrhage size calculated from tissue slices (r = 0.96, SEE = 0.92%, p less than 0.01), or by 51Cr labeling (r = 0.78, SEE = 1.5, p = 0.1). In the reperfusion group, T2 relaxation times in the infarcted hemorrhagic zone (58 +/- 9 msec) were significantly lower than the infarcted zones without hemorrhage (98 +/- 13 msec, p less than 0.001). In contrast, when compared with control (964 +/- 72 msec), T1 relaxation times were significantly increased in both infarct zones, either with (1,284 +/- 176 msec) or without (1,266 +/- 103 msec) hemorrhage. The selective shortening of T2 relaxation times in the hemorrhagic regions is consistent with the paramagnetic effects of deoxyhemoglobin. CONCLUSIONS: NMR imaging may provide a noninvasive approach for the detection and quantitation of intramyocardial hemorrhage. This observation may provide a means to further characterize pathological processes associated with acute myocardial infarction and assess the role of myocardial hemorrhage after reperfusion therapy. PMID- 1516172 TI - Health policy on blood cholesterol. Time to change directions. PMID- 1516173 TI - Health care policy for adults with congenital heart disease. The patient, the physician, and society. PMID- 1516174 TI - Routine prophylactic lidocaine administration in acute myocardial infarction. An idea whose time is all but gone? PMID- 1516175 TI - Stored iron and ischemic heart disease. Empirical support for a new paradigm. PMID- 1516176 TI - The adenosine saga: one more piece of the puzzle. But does it cause wall motion abnormalities? PMID- 1516177 TI - Prognostic and management role of cardiovascular ultrasound in surgically treated aortic stenosis. A picture (with pressure) is worth a thousand inotropic agents. AB - Cardiovascular ultrasound in the postoperative setting can be of value in helping to manage the patient who has undergone aortic valve replacement and is having a stormy postoperative course. Preoperative echocardiograms may not only detect the presence of those characteristics most likely to cause such a postoperative course but also select early postoperative pharmaceutical and volume interventions that are appropriate. It is hoped that the ability to preoperatively recognize those patients who are at high risk for developing intracavitary gradients will aid in appropriately managing them postoperatively and preventing the effects of prolonged hypotension secondary to intracavitary gradients. In addition, the early use of cardiovascular ultrasound in the postoperative patient to determine the functional and hemodynamic status of the ventricle, valvular structures, and pericardium may lead to appropriate early intervention, be it pharmacological or surgical, in patients who are having a complicated postoperative course. PMID- 1516178 TI - Regional thallium uptake in irreversible defects. PMID- 1516179 TI - Intracellular [Ca2+] in normal and diseased human myocardium. PMID- 1516180 TI - Plasma viscosity as a cardiovascular risk factor. PMID- 1516181 TI - Cardiac transplantation: recipient selection, donor procurement, and medical follow-up. A statement for health professionals from the Committee on Cardiac Transplantation of the Council on Clinical Cardiology, American Heart Association. PMID- 1516182 TI - Transesophageal echocardiography in infants and children with congenital heart disease. AB - TEE applications for children and infants with congenital heart disease are now clinically established and TEE is being used in most major pediatric cardiovascular centers. This technology has evolved to the point that it is capable of providing diagnostic quality imaging, even for small infants. With expanding technology and increasing experience, new and more sophisticated applications will be found for pediatric TEE. PMID- 1516183 TI - Migration of smooth muscle and endothelial cells. Critical events in restenosis. PMID- 1516184 TI - Prognostic determinants in hypertrophic cardiomyopathy. Prospective evaluation of a therapeutic strategy based on clinical, Holter, hemodynamic, and electrophysiological findings. AB - BACKGROUND: Patients with hypertrophic cardiomyopathy (HCM) frequently have arrhythmias and hemodynamic abnormalities and are prone to sudden death and syncope. An important need exists for improved risk stratification and definition of appropriate investigation and therapy. METHODS AND RESULTS: The relation of 31 clinical, Holter, cardiac catheterization, and electrophysiological (EP) variables to subsequent cardiac events in 230 HCM patients was examined by multivariate analysis. Studies were for cardiac arrest (n = 32), syncope (n = 80), presyncope (n = 52), ventricular tachycardia (VT) on Holter (n = 36), a strong family history of sudden death (n = 9), and palpitations (n = 21). Nonsustained VT on Holter was present in 115 patients (50%). Sustained ventricular arrhythmia was induced in 82 patients (36%). Seventeen cardiac events (eight sudden deaths, one cardiac arrest, and eight syncope with defibrillator discharges) occurred during a follow-up of 28 +/- 19 months. The 1-year and 5 year event-free rates were 99% and 79%, respectively. Two variables were significant independent predictors of subsequent events: sustained ventricular arrhythmia induced at EP study (beta, 3.5; p = 0.002) and a history of cardiac arrest or syncope (beta, 2.9; p less than 0.05). Only two of 66 patients without symptoms of impaired consciousness had a cardiac event (3-year event-free rate, 97%). In contrast, nonsustained VT on Holter was associated with a worse prognosis only in patients with symptoms of impaired consciousness: 11 of 79 symptomatic patients with VT on Holter (14%) had events versus only four of 85 symptomatic patients without VT on Holter (5%) (p = 0.057). Notably, none of 51 patients without symptoms of impaired consciousness in whom VT was not induced at EP study had a cardiac event. CONCLUSIONS: In HCM, VT on Holter is of benign prognostic significance in the absence of symptoms of impaired consciousness and inducible VT, and sustained VT induced at EP study, especially when associated with cardiac arrest or syncope, identifies a subgroup at high risk for subsequent cardiac events. PMID- 1516185 TI - Echocardiographic study of the morphology and growth of the aortic arch in the human fetus. Observations related to the prenatal diagnosis of coarctation. AB - BACKGROUND: In a study of normal and abnormal growth of the aorta before birth, high-resolution echocardiographic imaging of the aortic arch in 92 normal fetuses aged 16-38 weeks was used to establish normal values for aortic arch dimensions at varying gestational ages. METHODS AND RESULTS: From long-axis views of the aortic arch, the internal diameter of the aortic root, ascending aorta, transverse aortic arch, aortic isthmus, proximal descending thoracic aorta, and left common carotid artery were measured. Correlation coefficients for the diameter of each aortic arch segment when related to gestational age varied from r = 0.87 to r = 0.94 (p less than 0.001 for each), and growth curves were derived from the third and 97th percentiles around each linear regression analysis. In most of the fetuses, there was progressive tapering of the aortic arch, with the smallest diameter being at the isthmus. The ratio of the transverse aorta, isthmus, descending aorta, and aortic root to the ascending aorta remained relatively constant with gestational age, with mean values of 0.94, 0.81, 0.96, and 1.13, respectively. In five fetuses in whom a prenatal diagnosis of aortic coarctation was confirmed postnatally, transverse aortic and isthmic measurements fell on or below the third percentile for gestational age from the above data. In each case, the ratio of left common carotid artery to transverse aorta was greater than or equal to 0.73 compared with less than or equal to 0.62 for the 92 normal fetuses (mean ratios, 0.77 +/- 0.05 [SD] for coarctation versus 0.48 +/- 0.08 for normal fetuses; p less than or equal to 0.001). CONCLUSIONS: Use of normal growth curves for the developing aortic arch should facilitate the prenatal diagnosis of left heart and aortic arch abnormalities, particularly aortic coarctation, which until recently has been a difficult prenatal diagnosis to make with certainty. PMID- 1516186 TI - Cross-sectional early mitral flow-velocity profiles from color Doppler in patients with mitral valve disease. AB - BACKGROUND: Cross-sectional flow-velocity profiles from early mitral flow in 20 patients (10 with mitral regurgitation and 10 with mitral stenosis) were constructed from the velocity data from each point in sequentially delayed two dimensional digital Doppler ultrasound maps. METHODS AND RESULTS: The data suggested that the early mitral flow studied in an apical four-chamber view was variably skewed in both patient groups. The maximum flow velocity overestimated the cross-sectional mean velocity at the same time by a factor of 1.12-1.86. The maximum time-velocity integral was 1.13-1.77-fold greater than the cross sectional mean time-velocity integral. In patients with mitral regurgitation, the cross-sectional flow-velocity profile appeared to be most skewed at the level of the mitral leaflet tips. The level of the mitral annulus appeared to give the most homogenous flow-velocity distribution in both patient groups. CONCLUSIONS: When calculations of volume flow are based on pulsed Doppler ultrasound recordings with a single sample volume, the possibility of a skewed flow-velocity profile must be taken into account. PMID- 1516187 TI - Detection of coronary atherosclerosis in young adult hearts using intravascular ultrasound. AB - BACKGROUND: Coronary atherosclerosis has been demonstrated in young adults by postmortem pathology. Angiographic evaluation of coronary disease in young adults is limited by ethical issues and the insensitivity of angiography for detecting early pathology. Catheter-based intracoronary ultrasound has proven useful both in detecting and quantitating coronary disease, but the ultrasound appearance of young, angiographically normal, coronary arteries has not been well defined. METHODS AND RESULTS: Twenty-five subjects were examined with intracoronary ultrasound within 1 month of cardiac transplantation. Mean age of the donor hearts was 28 years (range, 14-43 years). Measurements of an index of intimal thickening were obtained at four left anterior descending coronary artery sites in each patient. All study patients had angiographically normal coronary arteries. Ultrasound in 14 subjects demonstrated a three-layered appearance of the coronary vessel wall with a mean intimal index of 0.16 +/- 0.07. The other 10 subjects, including all donors under the age of 25 years, had coronary vessel wall layers too thin to be imaged separately at the 30-MHz sound frequency. Five subjects had ultrasound evidence of focal intimal thickening greater than 500 microns. The donors of these hearts each had risk factors for coronary artery disease. Two subjects died within 5 weeks of their ultrasound study. Histological measurements of the vessel wall layers were similar to the corresponding ultrasound values. CONCLUSIONS: This study provides a reference for the intravascular ultrasound appearance of young adult coronary arteries and confirms pathology findings that young subjects with angiographically normal vessels have a range of coronary intimal thickening, which includes occasional evidence of focal, early atheromatous lesions. PMID- 1516188 TI - Declining incidence of ventricular fibrillation in myocardial infarction. Implications for the prophylactic use of lidocaine. AB - BACKGROUND: The purposes of the present investigation were 1) to track the incidence of primary ventricular fibrillation (VF) in the control and lidocaine treated groups in the randomized control trials (RCTs) of lidocaine prophylaxis against primary VF in acute myocardial infarction, with particular emphasis on the time frame of the randomized trial, and 2) to estimate the number of patients who must receive lidocaine currently to prevent one episode of VF. METHODS AND RESULTS: The following variables from RCTs published between 1969 and 1988 were entered into logistic regression models to predict the percent of patients developing VF: year of publication of the RCT, method of data analysis used in the RCT, route and technique of lidocaine administration, duration of monitoring for VF, and exclusion criteria before randomization (congestive heart failure/cardiogenic shock, ventricular tachycardia/VF, or bradycardia/atrioventricular block). Year of publication was a significant predictor of VF in both the control and lidocaine groups (p less than or equal to 0.002) even after adjusting for other covariates. Based on a univariate logistic regression model with year as the predictor variable, it was estimated that the incidence of primary VF in the control group fell from 4.51% in 1970 to 0.35% in 1990 and from 4.32% down to 0.11% for the lidocaine group over the same time period. Thus, about 400 patients would currently need prophylaxis with lidocaine to prevent one episode of VF. CONCLUSIONS: Present estimates of the risk:benefit ratio of lidocaine prophylaxis should consider the low risk of VF in control patients and the large number who need lidocaine prophylaxis to prevent one episode of VF. When added to the previously reported trend toward excess mortality in lidocaine-treated patients, these data argue against the routine prophylactic use of lidocaine in patients with acute myocardial infarction. PMID- 1516189 TI - Combined use of time and frequency domain variables in signal-averaged ECG as a predictor of inducible sustained monomorphic ventricular tachycardia in myocardial infarction. AB - BACKGROUND: Time and frequency domain analyses of signal-averaged ECG (SAECG) have several individual limitations, and the results of the two methods sometimes vary considerably. The purpose of this study was to determine whether the combined use of time and frequency domain variables facilitates identification of patients who will have ventricular tachycardia (VT) induced during programmed ventricular stimulation (PVS). METHODS AND RESULTS: Nine myocardial infarction (MI) patients with clinically documented sustained monomorphic VT (SMVT), 40 MI patients without clinical VT, and 30 normal healthy control subjects were evaluated. PVS using three extrastimuli and SAECG recording were performed in the MI patients on day 36 +/- 4 after infarction. Of 40 MI patients, SMVT was inducible in 14, sustained polymorphic VT in three, nonsustained monomorphic VT in three, nonsustained polymorphic VT in two, and no inducible arrhythmia was obtained in 18. There were significant differences between MI patients with inducible SMVT and without inducible SMVT in the following SAECG variables: filtered QRS durations (high-pass filter setting, 25, 40, and 80 Hz); low amplitude signal durations (LAS) under 10, 20, 30, and 40 microV (high-pass filter setting, 40 and 80 Hz); root-mean-square voltages (RMS) of the terminal 20, 30, 40, 50, and 60 msec (high-pass filter setting, 40 and 80 Hz); area ratio (area 20-50 Hz/area 0-20 Hz x 10(5)) of a 120-msec sampling interval starting 20 msec before QRS offset; factor of normality on lead X; and minimum value of the variables on lead X, Y, or Z. Stepwise logistic regression analysis selected only LAS under 30 microV (high-pass filter setting, 80 Hz) and area ratio as independent predictors of inducible SMVT. With these two variables, the predicted probability of inducible SMVT [p(VT)] was expressed as p(VT) = 1/[1+exp (6.2-0.11 LAS-0.01 area ratio)]. This function had 93% sensitivity, 81% specificity, 72% positive predictive value, 95% negative predictive value, and 85% predictive accuracy with greater than or equal to 0.3 as the criterion of a positive test. CONCLUSIONS: The combined use of time and frequency domain analysis of SAECG can enhance the accuracy of this technique as a screening test for results of PVS in MI patients without clinical VT. PMID- 1516190 TI - Transient intermittent lymphocyte activation is responsible for the instability of angina. AB - BACKGROUND: Blood clotting activation is an important component of the inflammatory response; the outbursts of unstable angina are usually associated with increased thrombin formation and coronary mural thrombosis. METHODS AND RESULTS: To investigate 1) whether monocyte activation is responsible for the enhanced thrombin formation during bursts of unstable angina and 2) what mechanism(s) might be responsible for monocyte activation, we studied patients with unstable angina (n = 31), stable effort angina (n = 23), left endoventricular thrombosis (n = 8), and control subjects (n = 44), measuring plasma fibrinopeptide A (FPA) levels and the capacity of monocytes to express procoagulant activity (PCA) and of lymphocytes to modulate this expression. Patients with unstable angina and patients with endoventricular thrombosis had significantly (p less than 0.0001) higher FPA plasma levels than patients with effort angina and control subjects. However, only monocytes from unstable angina patients expressed significantly increased PCA characterized as tissue factor like activity (units/10(5) monocytes, median and range; 120, 1.1-463.2 versus 10.8, 0.8-39.1 in control subjects; p less than 0.0001 versus the other groups). When 14 patients with unstable angina were restudied 8-12 weeks later, they showed neither elevated plasma FPA levels nor monocyte PCA. In unstable angina patients, there was a correlation between FPA and PCA (r = 0.56, p less than 0.001). For expression of PCA by monocytes, both an incubation of at least 2 hours with lymphocytes and direct monocyte-lymphocyte contact were needed. In reconstitution and cross-mixing experiments, only lymphocytes from patients with active unstable angina induced the expression of PCA by monocytes from both control and patient groups. CONCLUSIONS: The results demonstrate that the increased thrombin formation in unstable angina patients is due to the expression of tissue factor-like activity by activated monocytes. The monocyte activation appears to be a part of a lymphocytic cell-instructed response intermittently triggered by unknown factors. PMID- 1516191 TI - Different susceptibility to the development of nitroglycerin tolerance in the arterial and venous circulation in humans. Effects of N-acetylcysteine administration. AB - BACKGROUND: Tolerance to the effects of organic nitrates develops rapidly during continuous exposure to these drugs; its main mechanism seems to be an intracellular sulfhydryl group depletion. However, the relative susceptibility to the development of nitroglycerin tolerance of the arterial or venous circulation in humans is still a matter of dispute. METHODS AND RESULTS: Twenty patients with coronary artery disease underwent a continuous 24-hour nitroglycerin infusion followed by a bolus administration of N-acetylcysteine. Forearm blood flow (ml/100 ml/min) and venous volume (ml/100 ml) were measured by strain gauge plethysmography under control conditions, at the end of nitroglycerin titration, after 24-hour infusion, and after N-acetylcysteine; vascular resistance was calculated as mean cuff blood pressure divided by flow. After 24 hours of nitroglycerin infusion, the initial increase in venous volume was reduced 48% (p less than 0.01), whereas the acute effects on vascular resistance were not attenuated in the whole group. N-Acetylcysteine completely restored nitroglycerin venodilator effects in all 10 patients in whom attenuation of the venous effects was observed during the infusion period. CONCLUSIONS: The data indicate that the susceptibility to the development of nitrate tolerance in humans is higher in the venous than in the arterial circulation, and that the sulfhydryl group donor N acetylcysteine is extremely effective in reversing nitroglycerin tolerance in the venous circulation in humans. PMID- 1516193 TI - Emergent use of balloon-expandable coronary artery stenting for failed percutaneous transluminal coronary angioplasty. AB - BACKGROUND: The balloon-expandable intracoronary stent developed by Palmaz and Schatz is undergoing clinical evaluation for use in unfavorable anatomic situations and in the prevention of restenosis. Because the stent's mechanism of action would suggest effectiveness in salvaging certain percutaneous transluminal coronary angioplasty (PTCA) failures, we retrospectively examined the results of emergency unplanned coronary artery stenting for failed PTCA procedures, including acute occlusion. METHODS AND RESULTS: The study population consisted of all US patients receiving emergency unplanned stent implantation in a nonrandomized fashion at seven centers over a 2 1/2-year period (n = 56). All available medical records and angiograms were reviewed to determine retrospectively the reason for stenting: Group 1 consisted of 23 patients with a suboptimal angioplasty result; group 2 included patients with evidence of impending vessel closure after PTCA (n = 15); and group 3 were patients with frank acute occlusion after PTCA (n = 18). The immediate and final (30-day) results of stenting were examined with respect to major complications, which included death, need for coronary artery bypass graft surgery, and occurrence of myocardial infarction. Finally, restenosis rates (greater than or equal to 50% stenosis) based on follow-up angiography were calculated. Baseline characteristics of the study population included a mean +/- SD age of 58 +/- 11 years and a large prevalence of angiographic characteristics generally considered unfavorable for PTCA, which include lesion eccentricity (49%), intimal dissection (9%), or angiographically visible thrombus (6%). After conventional balloon angioplasty, there was an increased incidence of intimal dissection (74%) and thrombus formation (38%), and overall stenosis severity was unchanged (75 +/- 12% versus 70 +/- 27%, p = NS). Successful stent deployment was achieved in 55 (98%) of 56 patients with initial success (freedom from death, surgery, and infarction) in 52 (93%) of 56 patients. The success rate at 1 month fell to 71% primarily because of the occurrence of subacute stent thrombosis (16%) and its associated complications. Overall, major complications occurred in 16 (29%) of 56 patients within 30 days. The only predictor of subacute stent thrombosis in multiple stepwise logistic regression analysis was the presence of angiographically visible thrombus after stenting (p = 0.03). Angiographic restenosis was documented in eight (23%) of 35 eligible patients. CONCLUSIONS: Emergency stenting may be a useful and effective treatment for failed angioplasty. High initial success rates (greater than 90%) can be achieved, but subsequent complications, often related to subacute thrombosis, occur in a substantial portion of patients. Patients who receive stents on an emergency basis, particularly those with previous acute occlusion, should be considered to be at greater than usual risk for complications and receive more careful anticoagulation and follow-up. PMID- 1516192 TI - High stored iron levels are associated with excess risk of myocardial infarction in eastern Finnish men. AB - BACKGROUND: Iron can induce lipid peroxidation in vitro and in vivo in humans and has promoted ischemic myocardial injury in experimental animals. We tested the hypothesis that high serum ferritin concentration and high dietary iron intake are associated with an excess risk of acute myocardial infarction. METHODS AND RESULTS: Randomly selected men (n = 1,931), aged 42, 48, 54, or 60 years, who had no symptomatic coronary heart disease at entry, were examined in the Kuopio Ischaemic Heart Disease Risk Factor Study (KIHD) in Eastern Finland between 1984 and 1989. Fifty-one of these men experienced an acute myocardial infarction during an average follow-up of 3 years. On the basis of a Cox proportional hazards model adjusting for age, examination year, cigarette pack-years, ischemic ECG in exercise test, maximal oxygen uptake, systolic blood pressure, blood glucose, serum copper, blood leukocyte count, and serum high density lipoprotein cholesterol, apolipoprotein B, and triglyceride concentrations, men with serum ferritin greater than or equal to 200 micrograms/l had a 2.2-fold (95% CI, 1.2 4.0; p less than 0.01) risk factor-adjusted risk of acute myocardial infarction compared with men with a lower serum ferritin. An elevated serum ferritin was a strong risk factor for acute myocardial infarction in all multivariate models. This association was stronger in men with serum low density lipoprotein cholesterol concentration of 5.0 mmol/l (193 mg/dl) or more than in others. Also, dietary iron intake had a significant association with the disease risk in a Cox model with the same covariates. CONCLUSIONS: Our data suggest that a high stored iron level, as assessed by elevated serum ferritin concentration, is a risk factor for coronary heart disease. PMID- 1516194 TI - Morphological predictors of acute complications after percutaneous excimer laser coronary angioplasty. Results of a comprehensive angiographic analysis: importance of the eccentricity index. AB - BACKGROUND: Percutaneous excimer laser coronary angioplasty (ELCA) is a new technique for recanalization of arteries obstructed by coronary atherosclerosis. This study was conducted to assess the complication rate and determine the influence of clinical and angiographic characteristics on complications after ELCA. METHODS AND RESULTS: A detailed, quantitative, angiographic core laboratory analysis of patients undergoing ELCA was performed by two experienced angiographers who were not the primary laser angioplasty operators. Two hundred patients underwent 203 separate procedures on 220 lesions at three medical centers. Laser success was achieved in 180 lesions (81.8%) and procedural success in 199 (90.5%). Emergency coronary artery bypass graft (CABG) was required in five patients (2.5%). One patient suffered a Q wave myocardial infarction; there were no deaths. Also, acute closure and perforation occurred in 10 (4.5%) and three (1.4%) vessels, respectively. Coronary dissections after laser treatment were seen in 36 vessels (16.4%). Multivariate analysis found two independent preprocedural factors related to complications: eccentricity index, which is the percent deviation of the lesion lumen from the center of the artery (p = 0.0007), and proximal vessel diameter (p = 0.033). In addition, an abrupt proximal face of the lesion was associated with angiographic complications by univariate analysis (p = 0.051). Multivariate analysis showed the eccentricity index (p = 0.032) to be the only independent predictor for the occurrence of any one or more of the important complications (emergency CABG, perforation, acute closure, or Q wave myocardial infarction), whereas lesion angle greater than 45 degrees was a significant univariate predictor (p = 0.029). Other predictors of complications with balloon percutaneous transluminal coronary angioplasty, such as increased lesion length, rough edges, calcification, ulceration, and branch point, were not predictive of complications with the excimer laser. CONCLUSIONS: The degree of lesion eccentricity is the most powerful predictor of complications after ELCA. This and other morphological predictors may be of benefit in the selection of patients for ELCA as well as directing future development of this new technology. PMID- 1516195 TI - Anatomical progression of coronary artery disease in humans as seen by prospective, repeated, quantitated coronary angiography. Relation to clinical events and risk factors. The INTACT Study Group. AB - BACKGROUND: At present, there is extensive knowledge on the clinical course of coronary artery disease (CAD), whereas data on the underlying anatomical changes and their relation to clinical events are still limited. METHODS AND RESULTS: We investigated progression and regression of CAD prospectively over 3 years in 230 patients (average age, 53.2 years) with mild to moderate disease by applying quantitated, repeated coronary angiography. Minimal stenotic diameters, segment diameters, and percent stenosis were analyzed by the computer-assisted Coronary Angiography Analysis System (CAAS). Progression was defined either as an increase in percent stenosis of preexisting stenoses by greater than or equal to 20% including occlusions or as formation of new stenoses greater than or equal to 20% and new occlusions in previously angiographically "normal" segments. At first angiography, we found 838 stenoses greater than or equal to 20% (average degree, 39.3%) and 135 occlusions in the four major coronary branches (4.23 lesions per patient). At second angiography, 82 (9.8%) of the preexisting stenoses had progressed, 15 of them up to occlusion (1.8%; preocclusion degree averaging 46.6%; 29.7-65.6%). In addition, there were 144 newly formed stenoses (average degree, 39.2%) and 10 new occlusions. Hence, 25 (2.6%) of all stenoses had become occluded. Altogether, 129 patients (56.1%) showed progression: 68 (29.6%) with new lesions only, 27 (11.7%) with preexisting lesions, and 34 (14.8%) with both types. Regression (decrease in degree of stenoses greater than or equal to 20%) was present in 29 stenoses (3.6%) and 28 patients (12%). The incidence of new myocardial infarctions was low, with three originating from occluding preexisting stenoses and one from new stenoses; hence, only four (16%) of the 25 new occlusions led to myocardial infarctions. Risk factor analysis showed that cigarette smoking correlated significantly with the formation of new lesions (p = 0.001), whereas total cholesterol correlated with the further progression of preexisting stenoses (p = 0.017) but not with the incidence of new lesions. CONCLUSIONS: In patients with mild to moderate CAD, the angiographic progression is slow (in this study 18.7% of patients and 7% of stenoses per year) but exceeds regression (4.1% of patients and 1.2% of stenoses per year). Progression is predominantly seen in the formation of new coronary stenoses and less in growth of preexisting ones. Most of the stenoses were of a low degree (less than 50%), clinically not manifest including those going into occlusion and leading to myocardial infarction. Progression was influenced by risk factors, especially cigarette smoking (formation of new lesions) and high cholesterol levels (progression of preexisting stenoses). PMID- 1516196 TI - Lipids and lipoproteins in symptomatic coronary heart disease. Distribution, intercorrelations, and significance for risk classification in 6,700 men and 1,500 women. The Bezafibrate Infarction Prevention (BIP) Study Group, Israel. AB - BACKGROUND: Lipid and lipoprotein profiles of coronary heart disease (CHD) patients have usually not included data on high density lipoprotein cholesterol (HDL-C), except in small groups, and have not included information on women. Both aspects are meaningful in the evaluation of patients for risk classification and for the importance of HDL-C in dictating further evaluation. METHODS AND RESULTS: In the screening phase of a clinical trial, we obtained lipid and lipoprotein levels under Centers for Disease Control-standardized procedures in more than 6,700 men and 1,500 women aged 40-72 years. Mean total cholesterol (TC) was higher in women (by 15-24 mg/dl) but changed little with age. Mean HDL-C, however, progressively increased with increased age for both sexes (34.4 at age of less than 50 years to 37.5 mg/dl at age 65 or older in men and from 41.3 to 44.5 mg/dl for the respective age groups in women). Triglycerides (TG) were lower in elderly groups, particularly in men (151 mg/dl in 65-year-olds versus 189 in counterparts less than 50 years). The number of previous infarctions, severity of congestive heart failure, and severity of angina were negatively correlated with mean HDL-C in a dose-response manner, whereas the association with mean TG was inverted, creating a mirror image of that observed with HDL-C. More than half of patients (52%) with TC less than 200 mg/dl exhibited HDL-C levels consistent with the accepted "high-risk" range of less than 35 mg/dl, whereas an increasing percentage of desirable HDL-C level was found with increasing levels of TC (14% with HDL-C greater than or equal to 45 mg/dl at TC less than 200 mg/dl increasing gradually to 28% in patients with TC greater than 260 mg/dl). CONCLUSIONS: These results provide previously unavailable information on the lipid profile of female patients and appear to strongly establish the case for obtaining all three standard blood lipid determinations (TC, HDL-C, and TG) in coronary patients as well as in the framework of detecting and classifying individuals at high risk for CHD. PMID- 1516197 TI - Influence of dietary fat, apolipoprotein E phenotype, and sex on plasma lipoprotein levels. AB - BACKGROUND: The "Western" diet, sex, and apolipoprotein (Apo) E polymorphism have been implicated as codeterminants of lipid levels. METHODS AND RESULTS: In a retrospective analysis, we evaluated the combined impact of dietary fat, sex, and Apo E phenotype on lipoprotein levels in 67 subjects fed two contrasting, metabolically controlled diets: one a "Western" diet, with a low polyunsaturated to saturated (P:S) fatty acid ratio and the other a "therapeutic" diet, with a high P:S ratio. The high P:S diet compared with P:S diet exerted a far stronger predictive influence on lipoprotein concentrations than Apo E phenotype, sex, or the latter two factors combined. Apo E phenotype alone was associated with a stepwise increase in low density lipoprotein cholesterol (LDL-C), such that 3/2 less than 3/3 less than 4/3 on either the low or the high P:S diets. On the low P:S diet only, sex was shown to be a significant predictor of high density lipoprotein cholesterol (HDL-C) levels, with women greater than men, and the associated LDL/HDL ratio with men greater than women. On the high P:S diet, women displayed a dramatic fall in HDL-C, effectively raising the LDL/HDL ratio to equivalency with men and obliterating the sex influence seen with the low P:S diet. Controlled for dietary fat, Apo E and sex exerted independent, additive effects on lipoprotein levels on the low P:S diet only. Only the Apo E phenotype remained predictive on the high P:S diet. CONCLUSIONS: Women of the Apo E 3/2 phenotype stand to benefit the least from a high P:S diet because of reduction in the more "protective" HDL-C, whereas men of the 4/3 phenotype showed the greatest improvement in the LDL/HDL ratio. PMID- 1516198 TI - Lipoprotein lipids in older people. Results from the Cardiovascular Health Study. The CHS Collaborative Research Group. AB - BACKGROUND: Cardiovascular disease is the leading cause of death and disability in older people. There is little information about the distributions of risk factors in older populations. This article describes the distribution and correlates of lipoprotein lipids in people greater than or equal to 65 years old. METHODS AND RESULTS: Lipoprotein lipid concentrations were measured in 2,106 men (M) and 2,732 women (F) who were participants in the Cardiovascular Health Study, a population-based epidemiological study. Distributions of lipids by age and sex and bivariate and multivariate relations among lipids and other variables were determined in cross-sectional analyses. Mean concentrations of lipids were cholesterol: M, 5.20 +/- 0.93 mmol/l (201 +/- 36 mg/dl) and F, 5.81 +/- 0.98 mmol/l (225 +/- 38 mg/dl); triglyceride (TG): M, 1.58 +/- 0.85 mmol/l (140 +/- 75 mg/dl) and F, 1.57 +/- 0.78 mmol/l (139 +/- 69 mg/dl); high density lipoprotein cholesterol (HDL-C): M, 1.23 +/- 0.33 mmol/l (48 +/- 16 mg/dl), and F, 1.53 +/- 0.41 mmol/l (59 +/- 16 mg/dl); low density lipoprotein cholesterol (LDL-C): M, 3.27 +/- 0.85 mmol/l (127 +/- 33 mg/dl) and F, 3.57 +/- 0.93 mmol/l (138 +/- 36 mg/dl). The total cholesterol to HDL-C ratios were M, 4.49 +/- 1.29 and F, 4.05 +/- 1.22. TG, total cholesterol, and LDL-C concentrations were lower with increasing age, the last more evident in men than in women. TG concentration was positively associated with obesity (in women), central fat patterning, glucose intolerance, use of beta-blockers (in men), and use of estrogens (in women) and negatively associated with age, renal function, alcohol use, and socioeconomic status. In general, HDL-C had opposite relations with these variables, except that estrogen use was associated with higher HDL-C concentrations. LDL-C concentration was associated with far fewer variables than the other lipids but was negatively associated with age in men and women and positively correlated with obesity and central fat patterning and negatively correlated with renal function and estrogen use in women. There were no differences in total cholesterol and LDL-C concentrations among participants with and without prevalent coronary heart disease and stroke, but TG concentration was higher and HDL-C lower in men with both coronary heart disease and stroke and in women with coronary heart disease. CONCLUSIONS: Cholesterol and cholesterol/HDL-C ratio were lower and HDL-C higher than previously reported values in older people, suggesting that lipid risk profiles may be improving in older Americans. TG and HDL-C concentrations, and to a lesser extent LDL-C, were associated with potentially important modifiable factors such as obesity, glucose intolerance, renal function, and medication use. PMID- 1516199 TI - Rate-dependent effects of diltiazem on human atrioventricular nodal properties. AB - BACKGROUND: Tachycardia enhances the channel-blocking effects of antiarrhythmic drugs. In contrast to the extensive data regarding the rate-dependent effects of sodium channel blockers in humans, little is known about the frequency-dependent effects of calcium channel blockers on human atrioventricular (AV) nodal properties. Accordingly, the purpose of this study was to evaluate the importance of heart rate in modulating the electrophysiological effects of diltiazem in humans. METHODS AND RESULTS: Electrophysiological studies were performed in 25 patients. Sinus node, atrial, and AV nodal function were evaluated at multiple atrial rates under control conditions and after administration of one of three intravenous doses of diltiazem designed to produce low, intermediate, and high stable plasma concentrations (designated doses 1, 2, and 3, respectively). Results were analyzed in terms of the longest and shortest cycle lengths obtainable in each patient under control and drug conditions. Plasma concentrations of diltiazem were stable and averaged 43 +/- 4, 73 +/- 6, and 136 +/- 11 ng/ml for doses 1, 2, and 3, respectively. Sinus node recovery time, intra atrial conduction time, atrial effective refractory period, and HV interval were unaffected by diltiazem infusion. Effects of diltiazem were limited to changes in AV nodal parameters. Stable, dose-dependent increases in Wenckebach cycle length were observed after all three doses of diltiazem (increases of 54 +/- 13, 84 +/- 18, and 174 +/- 33 msec for doses 1, 2, and 3, respectively). Small nonsignificant increases in AH interval and atrioventricular effective refractory period (AVERP) were observed after dose 1 of diltiazem. At long cycle lengths, diltiazem caused modest increases in AH interval (3 +/- 4 and 25 +/- 8 msec for doses 2 and 3, respectively) and AVERP (36 +/- 12 and 70 +/- 25 msec). Drug effects were far greater at short cycle lengths (45 +/- 17 msec, 58 +/- 12 msec for AH interval and 80 +/- 24 msec, 163 +/- 41 msec for AVERP; p less than 0.05 versus values at long cycle lengths). At rapid rates, effects of diltiazem on AVERP substantially exceeded those on AV conduction, a result that could account for the beneficial effects of diltiazem during paroxysmal AV reentrant tachycardia by decreasing the excitable gap. CONCLUSIONS: Depressant effects of diltiazem on human AV nodal function are highly dependent on atrial rate; the rate-dependent actions on AV nodal refractoriness probably contribute to beneficial effects of diltiazem in patients with supraventricular arrhythmias. PMID- 1516200 TI - Effects of oxygen inhalation on skin microcirculation in patients with peripheral arterial occlusive disease. AB - BACKGROUND: Oxygen administration is currently used in clinical medicine to improve peripheral oxygen delivery to tissues threatened by ischemia. However, conflicting results have been reported on the effects of oxygen in ischemic areas. This study was aimed at investigating the effects of 40% oxygen inhalation on the skin microcirculation in the feet of patients with peripheral arterial occlusive disease (PAOD). METHODS AND RESULTS: Transcutaneous oxygen tension (tc PO2) was measured on the dorsal skin of the foot, and the nailfold microcirculation was investigated by a combination of laser Doppler flowmetry (LDF) and dynamic capillaroscopy (CBV) in the great toes of 17 legs of 11 patients, with 13 legs of eight normal subjects as a control group. Inhalation of oxygen induced a significant decrease of both the total (delta LDF, -307%, p less than 0.02) and nutritional (delta CBV, -17%, p less 0.002) skin microcirculation in normal legs compared with baseline values. A similar response was observed in 10 legs of patients who showed a significant increase of the tc PO2 (greater than or equal to 10 mm Hg) (delta LDF, -14%, NS; delta CBV, -13%, p less than 0.005). By contrast, both the total (+21%, p less than 0.03) and nutritional (+52%, p less than 0.05) circulation significantly increased in the seven legs without significant tc PO2 increase. In addition, the flow motion, which was impaired in the patients, was significantly (p less than 0.05) improved by oxygen inhalation. CONCLUSIONS: Inhalation of 40% oxygen induces a vasoconstriction in the skin microcirculation of toes of the normal subjects and patients with moderate PAOD but induces an increase of the skin microcirculation in patients with severe PAOD. PMID- 1516201 TI - Effect of intravenous adenosine infusion on myocardial perfusion and function. Hemodynamic/angiographic and scintigraphic study. AB - BACKGROUND: Myocardial perfusion imaging during adenosine-induced hyperemia with dipyridamole or adenosine is an accepted method to diagnose coronary artery disease (CAD) and risk assessment. The mechanism of perfusion abnormality may be caused by disparate flow responses or coronary steal. This study examined the relation between 201Tl perfusion pattern and hemodynamic/angiographic changes during intravenous adenosine infusion. METHODS AND RESULTS: Patients with suspected CAD underwent sequential hemodynamic, coronary arteriographic, and left ventriculographic studies simultaneously with 201Tl imaging during adenosine infusion (140 micrograms.kg-1.min-1 for 6 minutes). There were 33 patients with CAD and 12 patients without CAD. The 201Tl images (using single-photon emission computed tomography) were abnormal in 31 patients with CAD (sensitivity, 94%) and normal in the patients without CAD (specificity, 100%). In patients with and without CAD, there were significant increases in heart rate and cardiac output (p less than 0.0001) and decreases in systemic vascular resistance and blood pressure (p less than 0.0001). There was a 77 +/- 38% increase in pulmonary capillary wedge pressure in normal subjects and a 125 +/- 83% increase in patients with CAD (p = 0.02). ST segment depression was observed in 11 patients with CAD (33%). In CAD patients, there was no change in percent diameter or area stenosis measured quantitatively during adenosine infusion. In 15 patients, contrast left ventriculography was repeated during adenosine infusion. In these patients, 201Tl perfusion defects were seen in 31 of 75 segments (41%) whereas only six of 75 segments (8%) developed regional wall motion abnormality (p less than 0.001); the remaining segments showed either no change or improved function. The left ventricular ejection fraction did not change significantly (73% versus 75%). CONCLUSIONS: There is a disparity between the effects of adenosine on left ventricular perfusion and function; most patients with CAD have perfusion defects whereas the global and regional systolic function remains unchanged or improves. Diastolic left ventricular dysfunction is a probable mechanism of the increase in pulmonary capillary wedge pressure. PMID- 1516202 TI - Adenosine infusion for the reversal of pulmonary vasoconstriction in biventricular failure. A good test but a poor therapy. AB - BACKGROUND: Elevation of pulmonary vascular resistance is an important determinant of right ventricular function in patients with end-stage biventricular heart failure. Vasodilator drug therapy directed at the pulmonary vasculature is used in the hemodynamic assessment of patients for orthotopic heart transplantation, and therapy aimed at decreasing pulmonary vascular resistance and transpulmonary pressure gradient has been advocated in patients awaiting heart transplantation. Adenosine infusion has been shown to cause selective pulmonary vasodilatation in normal subjects and in patients with primary pulmonary hypertension but has not been assessed in patients with biventricular heart failure. METHODS AND RESULTS: Using two infusion doses, we studied the pulmonary and renal hemodynamic effects of adenosine on patients referred for heart transplantation (n = 21) and compared it with sodium nitroprusside (n = 18). Patients received 30% oxygen via face mask throughout the study. Adenosine at 100 micrograms/kg min achieved the same percentage fall in pulmonary vascular resistance as nitroprusside (41 +/- 6% versus 42 +/- 4%) and a greater and more consistent fall in transpulmonary pressure gradient (35 +/- 6% versus 9 +/- 30%, p less than 0.02). The mean arterial blood pressure fell by 16 mm Hg with nitroprusside but was unchanged by adenosine, indicating that in contrast to nitroprusside, adenosine acted as a selective pulmonary vasodilator. Despite this, cardiac index showed only a modest increase with adenosine (1.73 +/ 0.09 to 1.89 +/- 0.16 l.m-2, p less than 0.05), and there was a rise in pulmonary capillary wedge pressure from baseline at the higher dose (29.7 +/- 2.5 to 33.4 +/- 3.4 mm Hg, p less than 0.05). Renal blood flow was unchanged during adenosine infusion. CONCLUSIONS: Adenosine is a potent selective pulmonary vasodilator in patients with biventricular heart failure and is preferable to sodium nitroprusside as a test for the reversibility of pulmonary vasoconstriction. However, its deleterious effects on left atrial pressure make it unsuitable as a therapeutic agent in patients awaiting heart transplantation. PMID- 1516203 TI - Neurophysiological assessment of skeletal muscle fatigue in patients with congestive heart failure. AB - BACKGROUND: Recent research has demonstrated that patients with congestive heart failure (CHF) exhibit significant functional impairment of skeletal muscle and that these changes may be important determinants of exercise capacity. Although muscle strength may be mildly reduced, the most significant abnormality is markedly enhanced muscle fatigue. The goal of the present study is to determine whether accelerated fatigue is caused by impaired muscle activation, as a result of inadequate central motor drive or neuromuscular transmission, or by a change in the muscle itself. METHODS AND RESULTS: The study population consisted of nine patients with New York Heart Association class I-III CHF and eight sedentary, age and sex-matched control subjects. Maximal voluntary contraction force of the foot dorsiflexors (primarily the tibialis anterior) was quantified as a measure of muscle strength, isometric endurance was quantified by the time required for force to decline to 60% of maximal during a sustained maximal contraction, and dynamic endurance was defined as the number of maximal contractions required for force to decline to 60% of maximal under a protocol of six repetitions per minute with an incremental duty cycle. The degree of central motor drive failure was quantified by the degree of force augmentation produced by a superimposed tetanic stimulus delivered to the peroneal nerve during the initial maximal voluntary contraction and at the time when force during the sustained isometric contraction declined to 60% of maximal. Neuromuscular junction transmission was examined by quantifying the amplitude of the compound muscle action potential (M wave) in response to a single nerve stimulus during fatiguing exercise. Muscle strength was relatively preserved in the CHF patients versus the control subjects (93 +/- 41 versus 105 +/- 34 lb; p = NS), but isometric endurance (time to decline to 60%, 34 +/- 15 versus 54 +/- 19 seconds; p less than 0.02) and dynamic endurance (number of repetitions before decline to 60%, 30 +/- 6 versus 43 +/- 7 contractions; p less than 0.001) were both impaired. Tetanic nerve stimulation increased force by similar degrees in the two groups, and the amplitude of the M wave did not decline in either group during exercise. CONCLUSIONS: These findings indicate that enhanced muscle fatigue in patients with CHF is not caused by impaired central motor drive or an abnormality of neuromuscular junction transmission but rather by an abnormality in the muscle itself. PMID- 1516204 TI - Respiratory muscle function and dyspnea in patients with chronic congestive heart failure. AB - BACKGROUND: Patients with heart failure (HF) frequently experience exertional dyspnea. Using near-infrared spectroscopy, we have previously demonstrated accessory respiratory muscle deoxygenation during exercise in these patients by monitoring changes in light absorption at 760-800 nm. METHODS AND RESULTS: To investigate whether low-frequency respiratory muscle fatigue occurs, we performed supramaximal bilateral transcutaneous phrenic nerve stimulation before and after maximal bicycle exercise in 10 patients with HF (age, 62 +/- 10 years; ejection fraction, 18 +/- 7%) and six normal subjects (age, 50 +/- 8 years). Maximal rates of contraction and relaxation, peak twitch tension, and maximal transdiaphragmatic pressure (Pdi) were derived before and after exercise from analysis of six to 12 twitches obtained at functional residual capacity. Pdi, time in inspiration (Ti), time per breath (TTOT), respiratory gases, ratings of perceived dyspnea and fatigue, and 760-800 nm near-infrared spectroscopy absorbency changes of the serratus anterior muscle were measured throughout exercise. The tension time index (TTdi) of the diaphragm was derived. In both normal and HF subjects, all parameters of diaphragmatic function (i.e., maximal rates of contraction and relaxation, peak twitch tension, and maximal Pdi) were unchanged before and after exercise. Mean Pdi was comparable at rest (normal, 3.7 +/- 1; HF, 5.8 +/- 2.9 cm H2O; p = NS) but significantly greater in patients with HF at peak exercise (normal, 12.1 +/- 3; HF, 18.3 +/- 6.6 cm H2O; p less than 0.05). Ti/TTOT of both groups was similar at rest and throughout exercise. TTdi was significantly greater at rest (normal, 0.01 +/- 0.01; HF, 0.03 +/- 0.02; p less than 0.05) and at peak exercise (normal, 0.03 +/- 0.02; HF, 0.10 +/- 0.03; p less than 0.04) in patients with HF. Significant accessory respiration muscle deoxygenation was noted only in patients with HF (peak exercise; normal, -1 +/- 13; HF, 28 +/- 15 arbitrary units; p less than 0.01). Linear correlation analysis was performed between ratings of perceived dyspnea and parameters of pulmonary and diaphragmatic function. Significant correlations were observed between ratings of perceived dyspnea and maximal inspiratory and expiratory pressure, the TTdi of the diaphragm, near-infrared absorption changes, and forced expiratory volume in 1 second (FEV1) (all r greater than 0.5; p less than 0.05). Thus, respiratory muscle strength, work, and oxygenation were significantly correlated with the degree of dyspnea. CONCLUSIONS: We conclude that low-frequency diaphragmatic muscle fatigue does not occur despite accessory respiratory muscle deoxygenation during exercise in patients with HF. However, diaphragmatic work as assessed by the TTdi is dramatically increased in patients with HF and approaches levels previously shown to generate fatigue. The sensation of dyspnea appears closely related to respiratory muscle function. PMID- 1516205 TI - Localization of the fast and slow pathways in atrioventricular nodal reentrant tachycardia by intraoperative ice mapping. AB - BACKGROUND: Atrioventricular (AV) nodal reentrant tachycardia is classically described as a reentrant rhythm entirely contained within the compact AV node. Although the concepts of longitudinal dissociation of two intranodal pathways and a distal common pathway are accepted, the proximal portion of the circuit remains undefined. Current reports suggest that the two pathways may be separable by atrial tissue and not contained entirely within the compact node. METHODS AND RESULTS: We used an ice mapping method to demonstrate the slow and fast pathways of the reentrant circuit and their relation to the atrial septum around the AV node. Six patients with the usual form (slow-fast) of AV nodal reentrant tachycardia were mapped during surgery. In most patients, antegrade slow pathway localization was posterior and inferior to the compact AV node along the tricuspid annulus; in two patients, it was superior along the tendon of Todaro. Retrograde fast pathway localization was anterior or superior to the compact AV node in all patients. In all patients, anatomic distinction was made between the two pathways and the compact node. CONCLUSIONS: We conclude that no upper common pathway exists within the compact AV node in the usual type of nodal reentrant tachycardia and that the perinodal atrial tissue is a requisite part of the tachycardia circuit. PMID- 1516206 TI - Abnormal left ventricular intracavitary flow acceleration in patients undergoing aortic valve replacement for aortic stenosis. A marker for high postoperative morbidity and mortality. AB - BACKGROUND: We examined the clinical and echocardiographic characteristics of patients undergoing aortic valve replacement for aortic stenosis whose continuous wave Doppler studies showed abnormal intracavitary flow acceleration. METHODS AND RESULTS: The clinical and Doppler echocardiographic records of 53 consecutive patients undergoing aortic valve replacement for aortic stenosis were reviewed. Doppler echocardiography was performed at a mean of 6.6 days (range, 0-22 days) after surgery. Thirteen patients (group 1) had a dagger-shaped high-velocity systolic flow signal indicative of abnormal intracavitary flow acceleration on their postoperative Doppler study; group 2 comprised 40 aortic stenosis patients who underwent aortic valve replacement but had no postoperative evidence of abnormal intracavitary flow acceleration. Group 1 postoperative abnormal intracavitary flow velocities ranged from 1.8 to 6.8 m/sec (mean, 4.9 +/- 0.9 m/sec): Resulting dynamic gradients ranged from 10 to 184 mm Hg (mean, 104.6 +/- 32 mm Hg). Compared with group 2, group 1 patients had a distinctive ventricular geometry with more-pronounced hypertrophy, smaller cavities, and higher ejection fraction. Systolic anterior motion of the mitral valve did not accompany abnormal intracavitary flow acceleration in any patient. Six of 13 group 1 patients suffered postoperative hemodynamic compromise characterized by severe hypotension despite adequate pulmonary capillary wedge pressures; group 1 postoperative mortality was significantly greater than that seen in group 2 patients (38% versus 12%, p less than 0.05). CONCLUSIONS: Abnormal intracavitary flow acceleration after aortic valve replacement for severe aortic stenosis is associated with a distinctive ventricular geometry and supernormal systolic function but not systolic anterior motion of the mitral valve. Such flow acceleration appears to be a marker for increased postoperative morbidity and mortality. Preoperative and postoperative Doppler echocardiography may be useful in risk stratification and guiding therapy. PMID- 1516207 TI - Long-term effects of percutaneous laser balloon ablation from the canine coronary sinus. AB - BACKGROUND: Radiofrequency catheter ablation of left-sided accessory pathways is becoming the first line of therapy for patients with symptomatic Wolff-Parkinson White syndrome. Nevertheless, alternative ablation techniques merit development, at least as supplementary modalities for cases in which conventional ablation approaches may prove unsuccessful. We recently reported the short-term results with transcatheter laser balloon ablation from the coronary sinus in a canine model, proving that the procedure is feasible for the potential ablation of left sided accessory pathways. We now report the effects of percutaneous transcatheter laser balloon ablation in a chronic canine model. METHODS AND RESULTS: Twenty adult mongrel dogs were studied. After baseline coronary arteriography, left ventriculography, and coronary sinus angiography were obtained, 15 dogs received two or three consecutive laser doses from the coronary sinus of 30-40 W for 15-30 seconds, for a total cumulative energy of 1,200-2,400 J. The five remaining animals underwent a procedure consisting of balloon sham inflation without laser exposure and served as controls. After a mean follow-up of 6 weeks, the angiographic procedures were repeated, and the animals were killed. The mean extent of the fibrotic lesion was 15 mm long, 6 mm wide, and 4.5 mm deep and involved the coronary sinus wall, atrium, and, frequently, the summit of the posterior left ventricular wall. Six animals (four in the study group and two in the control group) showed asymptomatic narrowing of the coronary sinus lumen but always with total angiographic reconstitution due to extensive collateral circulation. The circumflex artery and mitral valve were intact angiographically and histologically in all animals. CONCLUSIONS: Percutaneous transcatheter laser balloon ablation via the coronary sinus produces a lesion that may be anatomically well suited for left-sided accessory pathway ablation. Although coronary sinus narrowing may occur, adverse physiological effects are unlikely due to the development of extensive collateral circulation. Systematic clinical studies of this new approach to catheter ablation appear warranted. PMID- 1516208 TI - Cellular mechanisms of differential action potential duration restitution in canine ventricular muscle cells during single versus double premature stimuli. AB - BACKGROUND: We tested the hypothesis that action potential duration (APD) restitution of normal ventricular muscle cells is different during double premature stimuli (S3) compared with a single premature stimulus (S2). We propose a possible ionic mechanism for such a difference. METHODS AND RESULTS: Action potentials and isometric tension were recorded simultaneously from isolated canine right ventricular trabeculae (2 x 2 x 10 mm) (n = 35). APD and tension restitution curves (APD) and peak tension versus diastolic interval [DI] of S2 and S3 were constructed by the extrastimulus method during pacing at 1,500 msec. The following results were obtained. 1) The APD restitution curve of S2 was different from that of S3. During the restitution of S2, an early biphasic upward hump was present at short DIs. In contrast, a smooth exponential rise was consistently seen during S3 restitution. 2) Peak tension remained significantly (p less than 0.001) lower during the restitution of S2 than during S3 restitution at all DIs tested. 3) The variation of APD during the initial 100 msec of DI was significantly longer during S3 than S2 (22 +/- 5 msec versus 41 +/- 5 msec, p less than 0.001). 4) Caffeine (2 mM, n = 5) and ryanodine (10 microM, n = 5) blocked cyclic variations of tension, presumably by blocking cyclic variations of intracellular calcium ion concentrations ([Ca2+]i), and eliminated the differences in APD restitution between S2 and S3. 5) Nisoldipine at high (5 microM) but not at lower (2 microM, n = 5) concentration eliminated the differences in restitution of both APD and tension between S2 and S3. 6) BAY K 8644 (100 nM, n = 5) had no effect on this difference. CONCLUSIONS: Greater variations of APD occur during the restitution of S3 than during S2 at short DIs. These differences appear to be caused by cyclic variations in tension and thus in [Ca2+]i. Calcium-sensitive outward currents could explain these differences in APD restitution. PMID- 1516209 TI - Dipyridamole potentiates the myocardial infarct size-limiting effect of ischemic preconditioning. AB - BACKGROUND: Recent studies implicated a key role for adenosine (ADO) receptor activation in the enhancement of ischemic tolerance by ischemic preconditioning. In this study, we aimed to test the hypothesis that dipyridamole, an ADO transport inhibitor, enhances the preconditioning effect. METHODS AND RESULTS: Six groups of rabbits underwent 30-minute coronary occlusion and 72-hour reperfusion. Infarct size (IS) and the area-at-risk (AR) were determined by histology and by use of fluorescent particles, respectively. IS expressed as the percentage of AR (%IS/AR) was 46.5 +/- 3.4% (n = 13) in control rabbits. Preconditioning with 2-minute ischemia tended to limit %IS/AR (%IS/AR, 35.5 +/- 3.5%, n = 9), and that possible protection was abolished by pretreatment with 10 mg/kg 8-phenyltheophylline (8-PT), an ADO receptor antagonist (%IS/AR, 43.9 +/- 5.8%, n = 9). Administration of dipyridamole (0.25 mg/kg) before the 2-minute preconditioning markedly limited %IS/AR to 13.8 +/- 2.6% (n = 12), indicating the potentiation of the preconditioning effect by this agent. Furthermore, this enhancement of preconditioning effect by dipyridamole treatment was significantly attenuated by 8-PT (%IS/AR, 27.6 +/- 2.1%, n = 11). Dipyridamole given before the 30-minute ischemia, without preconditioning, did not reduce %IS/AR (55.3 +/- 5.2%, n = 7), and a previous study from this laboratory had demonstrated that the present dose of 8-PT alone did not modify IS in the rabbit. CONCLUSIONS: Dipyridamole significantly potentiated the IS-limiting effect of preconditioning. This finding strongly supports the hypothesis that stimulation of ADO receptors by endogenous ADO, which builds up during preconditioning ischemia, mediates the increased ischemic tolerance afforded by preconditioning. PMID- 1516210 TI - Myocardial protective effects of adenosine. Infarct size reduction with pretreatment and continued receptor stimulation during ischemia. AB - BACKGROUND: We hypothesized that 1) endogenous adenosine released during ischemia conferred an inherent cardioprotection, and 2) a pretreatment dose of adenosine before ischemia would provide additional protection independent of hemodynamic effects. METHODS AND RESULTS: Thirty-six anesthetized New Zealand White rabbits underwent 30 minutes of regional ischemia produced by coronary occlusion followed by 2 hours of reperfusion. The adenosine group (ADO, n = 9) received a 5-minute pretreatment infusion of 140 micrograms/kg/min of adenosine before ischemia. A control group (SAL, n = 9) received saline before ischemia. To separate the effects of adenosine used as a pretreatment versus the effects during ischemia, a third group (ADO+SPT, n = 9) received adenosine as pretreatment followed by 10 mg/kg 8-p-sulfophenyl theophylline (8-SPT), an A1/A2-receptor antagonist given before ischemia, thus allowing pretreatment with adenosine but antagonizing its effects during ischemia. To preclude any protection from endogenous adenosine released during ischemia, the fourth group (SAL+SPT, n = 9) received saline as pretreatment and 8-SPT before ischemia. Area of necrosis within the area at risk (infarct size) was determined with tetrazolium and Evans blue stains, and transmural blood flow was measured using radioactive microspheres. Collateral blood flow in the area at risk was similar in all groups, as was the size of the area at risk. Infarct size was reduced by adenosine pretreatment (ADO, 8.4 +/- 7.2%) in contrast to saline vehicle (SAL, 27.8 +/- 6.3%; p less than 0.05 versus ADO). alpha 1/alpha 2-Receptor blockade after adenosine pretreatment abolished the ischemic protection provided by pretreatment adenosine (ADO+SPT, 42.7 +/- 8.3%; p less than 0.05 versus ADO). Finally, receptor blockade of endogenously released adenosine without adenosine pretreatment increased infarct size by 24% over the nonpretreated saline group (SAL+SPT, 51.5 +/- 9.0%; p less than 0.05 versus SAL). CONCLUSIONS: We conclude that 1) endogenous adenosine building up during ischemia is cardioprotective, and 2) pretreatment with adenosine confers cardioprotection independent of hemodynamic effects. Whether pretreatment effects of adenosine subsequently modulate the effects of endogenous adenosine (through alterations in receptor population or sensitivity) or endogenous and exogenous adenosine represent additive compartments is unclear. PMID- 1516211 TI - Contemporary considerations in exercise ECG testing. PMID- 1516212 TI - Trends in noncardiac chest pain. PMID- 1516213 TI - A practical approach to coma diagnosis in the unresponsive patient. AB - Diagnosis of coma in the unresponsive patient can be done in a relatively short time by making key observations that will confirm disease of either the brain stem or the hemispheres, the two locations in which coma originates. Determining the location of the lesion is the primary goal in early assessment of the unresponsive patient. Examination of the patient's eyes is the single most important step in understanding coma. PMID- 1516214 TI - Calcium-channel blocking agents as therapy for amphotericin B nephrotoxicity. AB - Amphotericin B is a broad-spectrum antifungal agent shown to be effective in the treatment of systemic fungal infections. Unfortunately, therapeutic doses are often associated with a variety of adverse effects, including nephrotoxicity. Studies of the deleterious effects of amphotericin B on the renal microvasculature are yielding clues to sparing kidney function. In selected patients, concomitant use of a calcium-channel blocker may prevent the nephrotoxic effects of amphotericin B and allow full therapeutic doses to be used. PMID- 1516215 TI - Pharmacotherapy of multiple sclerosis: current status. AB - Pharmacotherapy plays an important part in the overall management of patients with multiple sclerosis. Most therapies directed at altering the natural history of the underlying disease process are only partially effective or are controversial or experimental. However, many effective symptomatic therapies are available to the clinician. The action and uses of corticosteroids in multiple sclerosis are discussed, and approaches to the treatment of spasticity, paroxysmal disorders, bladder dysfunction, cerebellar ataxia, neurobehavioral manifestations, fatigue, and acute and chronic pain in patients with multiple sclerosis are examined. PMID- 1516216 TI - Doppler echocardiographic assessment of constrictive pericarditis, cardiac amyloidosis, and cardiac tamponade. AB - Doppler echocardiography is useful in assessing diastolic dysfunction. Pulsed wave Doppler echocardiographic interrogation of the atrioventricular valves and the central veins has been used in conjunction with respiratory monitoring to characterize abnormal diastolic function of the heart in diseases such as constrictive pericarditis, restrictive cardiomyopathy, and cardiac tamponade. Constrictive pericarditis has distinct Doppler flows with marked respiratory variation because the pericardial shell separates the intracardiac pressures from intrathoracic pressure. This is not the case with restrictive cardiomyopathy, as in cardiac amyloidosis. Cardiac amyloidosis shows a spectrum of the Doppler flows which evolve as the disease progresses from abnormal relaxation in the early phase to pseudo-normal in the intermediate phase and to restrictive in the advanced phase. Doppler echocardiography can be used to assess the hemodynamic significance of pericardial effusion and to detect cardiac tamponade. PMID- 1516217 TI - Primary angiitis of the central nervous system: diagnostic criteria and clinical approach. AB - Primary angiitis of the central nervous system has until recently been considered rare, usually progressive, and untreatable. In 1987, preliminary diagnostic criteria for the disorder were proposed in the hope of gaining a more accurate description of the disease. We used these criteria in reviewing all cases reported in the English language (99 cases) and those seen at The Cleveland Clinic Foundation (9 cases). We believe that the disorder is heterogeneous, and has a better prognosis than previously thought. Furthermore, a relatively benign subset of this disorder, termed "benign angiopathy of the central nervous system," can be defined on clinical grounds. We propose a revised set of diagnostic criteria and a practical approach to treatment. PMID- 1516218 TI - Lung and heart-lung transplantation: the state of the art. AB - Lung and heart-lung transplantation is one of the most rapidly evolving transplantation fields. Survival has been improving with better patient selection, better graft preservation, and better immunosuppression. This paper outlines criteria for patient selection, reviews the surgical options involving lung transplantation, and discusses factors influencing morbidity and survival in these patients. The Cleveland Clinic Foundation experience with these procedures is presented. Lung and heart-lung transplantation has emerged from the experimental realm to the therapeutic, and can now be offered as an effective treatment option to many patients with previously fatal heart and lung disorders. PMID- 1516219 TI - Viral hepatitis in the 1990s, Part I: Current principles of management. AB - Recent years have brought major advances in the diagnosis and treatment of viral hepatitis. Treatment of acute uncomplicated hepatitis is supportive rather than curative. Treatment of fulminant hepatic necrosis is directed towards preventing and treating complications while preparing suitable patients for liver transplantation. Corticosteroids do not improve survival rates in patients with fulminant hepatic necrosis and should be avoided in nearly all patients with hepatitis A. Although liver histology in acute viral hepatitis is highly characteristic, biopsy is usually superfluous, except in transplant patients with acute hepatic dysfunction. Hepatitis A virus infection is frequently asymptomatic, and data on its incidence are poor. The virus is frequently transmitted before the patient becomes ill; therefore, curtailing hepatitis A spread depends in large measure on hygienic practices. Passive immunization is possible with immune globulin. Inactivated and attenuated vaccines may be licensed within the next 2 years. PMID- 1516220 TI - Circadian rhythms and migraine. AB - To determine whether migraine exhibits a circadian rhythm or occurs randomly throughout the day, we analyzed the time of migraine onset in 15 migraine suffers (migraineurs) over 20 weeks. The patients suffered 211 migraine attacks over 20 weeks (range 3 to 30, median 13). Twelve of the 15 migraineurs had 50% or more of headache onsets during a 4-hour block of time. As a group, the migraineurs showed a circadian variation in migraine onset, with a marked increase in attacks between 6 AM and 8 AM, peak frequency of migraine onset between 8 AM and 10 AM, and a dramatic decrease in frequency between 8 PM and 4 AM. The circadian rhythm of migraine onset parallels that of myocardial infarction, platelet aggregability, plasma cortisol, and plasma catecholamines. These associations suggest that alteration of vasomotor tone may be involved in the initiation of migraine attacks. PMID- 1516221 TI - Lung transplantation is here to stay. PMID- 1516222 TI - Wolman disease: morphological, clinical and genetic studies on the first Scandinavian cases. AB - On the Aland Islands, a 1-month-old girl was diagnosed as having Wolman disease. The diagnosis was confirmed neurochemically; a decreased activity of acid lipase was noted in the proband and her parents had typical carrier values. This is the first Scandinavian case reported. The skin biopsy revealed cytoplasmic accumulations identical to those noted in two sibs who highly probably had Wolman disease during the 1950s. Both these sibs died at the age of about 3 months and presented a heavy accumulation of lipid material in lymph nodes, spleen, adrenal glands, liver, gut, and also some pathological alterations in other organs. Electron microscopic findings from deparaffinized samples showed cytoplasmic accumulation of lipid material similar to that noted in Wolman disease. Genealogical analyses revealed that the index families had ancestors from the same restricted area and also common ancestors during the 17th century. The parents of the two affected sibs were born on a small island and were related in many different ways. On the basis of genealogical studies and other genetic investigations performed, the importance of founder and drift effect for manifestations of rare hereditary disorder in isolates is stressed. PMID- 1516223 TI - Congenital heart defects, hamartomas of the tongue and polysyndactyly in a sister and brother. AB - We report a sister and brother with congenital heart defects, hamartomas of the tongue and polydactyly. Both had coarctation of the aorta, which was repaired in early infancy. In addition, the girl had atrioventricular canal. She died postoperatively at age 4 years. The boy had subaortic stenosis and died of pneumonia at age 2 years. Both children had normal psychomotor development. The parents were healthy and unrelated. The familial occurrence could be due to a previously unrecognized autosomal recessive syndrome or parental gonadal mosaicism for a dominant syndrome. PMID- 1516224 TI - Time of pubertal onset, testosterone levels and intelligence in 47,XXY males. AB - This study examined the relations between verbal and performance IQs, time of pubertal onset and testosterone levels from 13 to 16 years of age in a sample of 30 males with a supernumerary X chromosome. The findings indicated that verbal IQs measured prior to puberty, during puberty and at mid-adolescence were strongly related to relatively early pubertal onset and testosterone levels. Performance IQs had little or no relationship with the same variables. The results are discussed in terms of several different psychobiological models. PMID- 1516225 TI - Elevated serum levels of creatine kinase BB in autosomal dominant osteopetrosis type II--a family study. AB - A markedly elevated BB isoenzyme fraction of serum creatine kinase was noted in four male siblings and correlated with typical radiographic findings of autosomal dominant osteopetrosis Type II (ADO Type II). Patients with other sclerosing bone diseases had no elevation of CK-BB. The precision of the electrophoretic mobility patterns and correlation by I-125 tagged radioimmunoassay method confirms that this is CK-BB. We postulate that the dysfunctional and/or immature osteoclasts in ADO are more dependent on CK-BB than on the usual tricarboxylic acid cycle for the production of energy. The correlation of marked elevation of serum CK-BB with radiographic evidence of ADO Type II may prove to be of value as a biologic marker in the early diagnosis of the illness and lead to better understanding of the metabolism of bone. PMID- 1516226 TI - DNA screening of hyperlipidemic Afrikaners for familial hypercholesterolemia. AB - Three different point mutations of the low-density lipoprotein receptor (LDLR) gene are responsible for familial hypercholesterolemia (FH) in about 90% of Afrikaner patients. Screening of hyperlipidemic Afrikaner individuals for these founder-related mutations was performed to determine the distribution of the mutations in individuals with different lipid profiles, and to provide guidelines for screening of the mutations in hyperlipidemics. Rapid DNA methods, based on restriction enzyme analysis or allele-specific hybridisation of enzymatically amplified genomic DNA, have been used to analyse the LDLR gene mutations in four groups of Afrikaner individuals. Group 1 included 84 individuals in whom FH was diagnosed on clinical data. Groups 2-4 included 89 hyperlipidemic individuals who did not fulfil the criteria for inclusion in the FH study group. The founder related LDLR gene mutations were present in 36% of the hyperlipidemics whose clinical diagnosis excluded them from the FH study group. This indicates that conventional methods for the diagnosis of FH, based mainly on lipid determinations and a family history of coronary heart disease, do not always allow an accurate diagnosis of the disease. Screening of hyperlipidemic Afrikaner individuals for specific founder-related LDLR gene mutations can provide a definite diagnosis of FH, which may lead to better counselling and optimal treatment. PMID- 1516227 TI - Confirmation of true mosaic trisomy 20 in a phenotypically normal liveborn male. AB - A new case of prenatally detected mosaic trisomy 20 (79% trisomy 20 cells in amniocyte cultures) that was confirmed in newborn tissue is presented. A healthy male infant was delivered at term, with no dysmorphology or apparent malformations; this baby is developing normally. Twenty-five percent of foreskin and 17% of fetal cord cells also showed trisomy 20, while no trisomic cells were detected in newborn blood. High frequency mosaicism for trisomy 20 in this case was thus due to true embryonic origin. Extensive counseling and prenatal follow up in this case led to an unaffected liveborn, and guarded optimism may be warranted for future cases of mosaic trisomy 20 detected prenatally. PMID- 1516228 TI - Pitted enamel hypoplasia in tuberous sclerosis. AB - Thirty patients with tuberous sclerosis (from 29 different families) were examined for evidence of macroscopically visible pitted enamel hypoplasia. Of 23 patients with permanent teeth, 11 (48%) showed multiple enamel pits (mean 4.6 pits, range 3-9), but none were seen in six patients with deciduous teeth. Five of 563 controls (0.88%) had similar pitted enamel hypoplasia. Simple dental examination may be a useful adjunct in the assessment of patients with permanent teeth when a diagnosis of tuberous sclerosis is being considered, but is less likely to be helpful in the pre-school child. PMID- 1516229 TI - DNA deletion in patients with von Recklinghausen neurofibromatosis. PMID- 1516230 TI - Autism and ring chromosome 18 mosaicism. PMID- 1516231 TI - Linkage analysis in properdin deficiency families: refined location in proximal Xp. AB - Properdin is a component of the alternative activation pathway of the complement system. Deficiency or dysfunction of the protein is inherited in an X-linked recessive manner. Affected males have an increased risk of developing meningococcal disease. Six multi-generation families with different types of properdin deficiency were analyzed using microsatellite and other polymorphisms on the X chromosome. Based on multipoint data, it was found that the disease gene maps close to DXS255 (Zmax = 13.3 at theta max = 0.00) and DXS426 (Zmax = 12.9 at theta max = 0.00) on the Xp-arm near the centromere. There was no indication of genetic heterogeneity among the six families analyzed. Thus it is now possible to perform accurate DNA-based determination of the inheritance of the mutation in affected families. PMID- 1516232 TI - Characterization of aerobic non-lipophilic coryneforms from human feet. AB - Aerobic coryneform bacteria from human feet have been studied by analysis of the cell-wall sugars, lipids and diamino acids and by phenotypic tests. Although many isolates studied fall into the established genus Brevibacterium at least two previously unreported taxa of coryneform have been identified bringing the number of aerobic, non-lipophilic taxa known on skin to four. Simple tests can be used to distinguish between these taxa. Studies on the human skin flora continue to reveal the diversity of organisms present. PMID- 1516233 TI - Junctional epidermolysis bullosa: a mild variant in two Indian sisters. AB - Two sisters developed a bullous skin disease in early childhood. The disease had features of junctional epidermolysis bullosa but differed clinically from previously recorded variants. PMID- 1516234 TI - Oral papillary plasmacytosis resembling candidosis without demonstrable fungus in lesional tissue. AB - Two cases with exuberant papillary and nodular hyperplasia of the hard and soft palates are described. Both were elderly edentulous men with bilateral angular stomatitis. The papillary hyperplasia extended as far as the epiglottis and was associated with swelling and fissuring of the upper lip in patient 1. In patient 2, the palatal change extended to the maxillary gingiva and was associated with smooth plaques and fissuring of the dorsal tongue. Histology of both cases showed a dense polyclonal plasma-cell infiltrate with overlying epithelial hyperplasia, parakeratinization and neutrophil micro-abscesses suggesting Candida infection but fungal elements could not be demonstrated. Patient 1 also showed defective cellular immunity to Candida antigen which was reversed by treatment with ketoconazole and levamisole, antedating clinical improvement. PMID- 1516235 TI - Unusual manifestations of primary cutaneous amyloidosis in association with Raynaud's phenomenon and livedo reticularis. AB - A patient with unusual manifestations of primary cutaneous amyloidosis, including macules, papules, oedematous plaques and urticarial lesions is described. Raynaud's phenomenon and livedo reticularis were an associated finding. During the acute phase, single doses of systemic corticosteroids resulted in an impressive, long-lasting improvement in cutaneous manifestations. PMID- 1516236 TI - Unusual cutaneous lesions associated with chronic myelomonocytic leukaemia. AB - A 69-year-old man presented with unusual nodular cutaneous lesions of 3 years duration predominantly involving the chest, upper back and scalp. Histopathological changes in biopsy specimens from affected skin resembled those seen with granuloma annulare even though there was a lack of epithelioid cells. Based on the sluggish course of the condition, leukocytosis with monocytosis in peripheral blood and the findings on electron microscopic examination of peripheral blood cells, he was diagnosed as having chronic myelomonocytic leukaemia (CMMoL). At lower magnification under the electron microscope, the nodular skin lesions showed pleomorphic cell features with monocytes and histiocytic cells of abnormal appearance. The skin lesions were thus considered to be an unusual type of leukaemia cutis. PMID- 1516237 TI - Long-term undiagnosed syphilis with clinical presentation of meningitis. AB - A 43-year-old woman, with an 11-year history of progressive cutaneous lesions, was considered to have granuloma annulare and was treated as such for 4 years. She then developed chronic meningitis. Serological investigation revealed active syphilis. Appropriate antibiotic treatment led to a rapid resolution of the clinical symptoms. The recent reports of similar cases indicate the importance of an adequate knowledge of clinical manifestations and pathological patterns of syphilis. PMID- 1516238 TI - Systemic sclerosis sine scleroderma presenting with vitiligo-like depigmentation and interstitial pulmonary fibrosis. AB - We report a case of systemic sclerosis sine scleroderma in which vitiligo-like depigmentation and early interstitial pulmonary fibrosis predominated. The pigmentary changes occurring in systemic sclerosis are reviewed and the distinctive features of the case discussed. PMID- 1516239 TI - Mycosis fungoides mimicking perioral dermatitis. AB - A 71-year-old woman under PUVA-treatment for mycosis fungoides developed erythematous patches around the nasolabial folds and papules on the chin with clinical features of perioral dermatitis. Histology showed a specific infiltrate of mycosis fungoides with predominance of medium to large-sized pleomorphic lymphocytes and immunoblasts. Immunohistochemical analysis revealed the T phenotype of the neoplastic cells. Small clusters of B-lymphocytes could also be observed within the infiltrate. Perioral dermatitis-like lesions can be added to the spectrum of rare and unusual clinical manifestations of mycosis fungoides. PMID- 1516240 TI - Subacute cutaneous lupus erythematosus in a patient with Crohn's disease. AB - A case of anti-Ro (SS-A) antibody-positive subacute cutaneous lupus erythematosus (LE) occurring in a 47-year-old male with Crohn's disease is described. This is a previously undescribed association. PMID- 1516241 TI - Urticarial vasculitis, IgA deficiency and C1 esterase inhibitor deficiency in the presence of an IgG monoclonal gammopathy--a case report. AB - A female patient, currently aged 40, has attended our Lupus Clinic for 8 years with a clinical picture of urticarial vasculitis, joint pains, severe myalgias and abdominal pain which has occurred in bouts at irregular intervals. She has been found to have consistently reduced C4 levels, C1-esterase inhibitor deficiency and a persistent monoclonal band in the gamma region on electrophoresis. Her serum IgA level has been continuously low. Her symptoms have failed to respond to antihistamines and a variety of other measures but have been partially alleviated by immunosuppressive therapy ('pulsed' cyclophosphamide). We believe that this is the first patient described showing this combination of clinical and laboratory features. PMID- 1516242 TI - Short-lived cold challenge has no effect on normal human skin. PMID- 1516243 TI - Shower jet dermatitis. PMID- 1516244 TI - Dermatological out-patient activity per region in England. PMID- 1516245 TI - Sarcoidosis and giant cell arteritis. PMID- 1516246 TI - The immunogenetic background of scleroderma--an overview. AB - Currently it may be stated that the MHC associations in scleroderma support the classification of disease subsets, but in no ethnic group is the overall association strong enough for clinical use. In different ethnic groups, the distribution of MHC alleles varies, as does the degree of linkage disequilibrium between alleles of the linked loci. This concept is even relevant to relatively close populations. Thus Whiteside noticed that, if those patients referred from more than 100 miles from the study centre were excluded, then the strength of the DR1 association increased. The environmental contribution to scleroderma is unknown, except in the case of toxin or solvent associated disease. Different causal environmental agents found in different global regions might result in separate MHC associations and hence explain the discrepancies noted above. There are indications that associations between specific subsets of SSc patients and genetic markers will assume greater importance both diagnostically and prognostically. The lung fibrosis group look prime candidates, for example. Genetic markers are also a useful means of relating chemically-induced SSc-like disorders to the classical disease. Vinyl chloride disease provides an example. There is much heterogeneity within the disease, in terms of extent of skin involvement, severity, and of organ involvement. It is clear that the different clinical subsets of scleroderma are characterized by different associated MHC alleles. There are also many cases of clinical overlap with related diseases, and certain of these diseases have a different HLA association, which could detract from the primary HLA type associated with SSc.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1516247 TI - Cutaneous manifestations in systemic trichosporonosis. AB - Trichosporonosis due to Trichosporon beigelii is increasingly recognized in neutropenic immunocompromised patients. We report the clinical and histological presentation of three cases, as well as a study of the prevalence of T. beigelii colonization of normal-looking skin in patients receiving intensive chemotherapy for cancer. PMID- 1516248 TI - Erythema elevatum diutinum: a clinicopathological study. AB - Erythema elevatum diutinum is a syndrome of vasculitis in which lesions, typically over the extensor surfaces, showed a mixed inflammatory infiltrate on biopsy. We describe a series of 13 patients. The most common association in our series was with hypergammaglobulinemia; both mono and polyclonal. Chronic infection, not streptococcal, was a less frequent finding although two of three patients had a positive reaction to the intradermal injection of streptococcal antigen. Dapsone remains the initial treatment of choice. PMID- 1516249 TI - Actinic reticuloid: action spectra and UVA protection factor sunscreens. AB - This study compares the action spectra on two new patients with actinic reticuloid (AR), with one previously reported patient. All three patients had exquisite photosensitivity in the UVB range being up to 27 times more sensitive than controls. Sensitivity also increased into the UVA Range, all up to 335 nm and, one into the visible. Their photosensitivity made evaluation of the Sun Protection Factor (SPF) of selected, more recent, high-numbered sunscreens easier to compare, because of the shorter time of the minimal erythema dose when tested with a solar simulator. A sunscreen containing butyl methoxydibenzoylmethane (Parsol 1789) with an overall SPF of 16 was not as effective at protecting the actinic reticuloid patients as a higher SPF numbered sunscreen containing a benzophenone (SPF of 40). The Parsol 1789 gave a protection value of 5 in the UVA Range, compared to one of 3 given by the sunscreen containing benzophenone. The SPFs of seven of these commerically available high-numbered sunscreens were compared with controls. PMID- 1516250 TI - The bare:ensheathed anagen root ratio as a function of the speed of epilation. AB - Small tufts of chest hair were epilated at different rates and the roots classified as to growth phase, presence or absence of root sheaths and whether the shafts were fractured. With respect to anagen roots, a slow epilation gives bare roots whereas an increase in the rate of epilation increases the proportion of ensheathed roots. As the rate of epilation increases, the proportion of fractured hair shafts increases. These findings are relevant to epilation used as a diagnostic procedure because it is not possible to have both a high proportion of well-formed ensheathed anagen roots without some breakages. PMID- 1516251 TI - The spleen? Who needs it anyway? PMID- 1516252 TI - Characterization of anti-interferon-alpha antibodies appearing during recombinant interferon-alpha 2a treatment. AB - Patients with malignant midgut carcinoid tumours received recombinant interferon alpha 2a (rIFN-alpha 2a) or rIFN-alpha 2a and chemotherapy (streptozocin and doxorubicin) for 6 months, and then rIFN-alpha 2a alone. Antibodies, mainly of IgG type, binding to rIFN-alpha 2a developed in nine of 22 patients (41%), as determined by immunoassay. In seven patients, antibodies also neutralized the biologic (anti-viral) activity of rIFN-alpha 2a. Anti-IFN-alpha 2a antibodies were equally frequent in both sexes and treatment groups, but were not observed in those patients (n = 8) that had previously received other types of IFN. Antibodies appeared after a median of 6 months of rIFN-alpha 2a treatment and had a median duration of 6 months. The anti-IFN-alpha 2a antibody titres declined with time with no obvious relation to change of therapy, also during continued IFN-alpha 2a treatment. High titres of neutralizing antibodies appeared to impair anti-tumoural effects in individual potential responders. Anti-IFN-alpha 2a antibodies further examined in six patients bound to native IFN-alpha subtypes present in both allogenic and autologous leucocyte IFN-alpha. Such autoantibodies neutralized the biologic activity of autologous IFN-alpha in two patients, and in a third were partially neutralizing. PMID- 1516253 TI - A comparison of anti-lymphocyte immunotoxins containing different ribosome inactivating proteins and antibodies. AB - Immunotoxins were prepared with several single-chain ribosome-inactivating proteins (RIPs type 1) and with the A-chain of ricin linked to the F(ab')2 fragment of sheep anti-mouse IgG. The cytotoxic activity of these conjugates was tested on human lymphocytes pretreated with an anti-CD3 murine MoAb. The immunotoxins inhibited DNA synthesis in phytohaemagglutinin (PHA)-stimulated lymphocytes with IC50S (concentrations causing 50% inhibition) ranging from 8.9 x 10(-13) to 5.7 x 10(-11) M (immunotoxins containing dianthin 32, saporin, pokeweed antiviral protein from seeds (PAP-S), bryodin, momordin, momorcochin, and trichokirin), 1 x 10(-8) M (immunotoxin containing gelonin) and 5 x 10(-9) M (immunotoxin containing ricin A-chain). The immunotoxin containing saporin linked to the anti-mouse IgG F(ab')2 fragment was also highly toxic to human lymphocytes pretreated with anti-CD2, -CD3, -CD5 and -CD45 MoAbs, with IC50S less than or equal to 10(-11) M. Immunotoxins were prepared also with saporin linked to MoAbs against various CD antigens. The immunotoxin prepared with the anti-CD3 antibody had the highest specific cytotoxicity to human lymphocytes. PMID- 1516254 TI - Predictors of infection in chronic lymphocytic leukaemia (CLL). AB - A group of patients with chronic lymphocytic leukaemia (CLL) were studied to determine whether particular clinical and laboratory parameters might help to identify those patients at risk of recurrent infection who would benefit from immunoglobulin replacement therapy. The case notes of 59 patients were reviewed with regard to stage and duration of disease, chemotherapy and frequency of infection over the preceding 2 years. Serum IgG levels and specific antibodies to tetanus, diphtheria and pneumococcal capsular polysaccharide were measured at the end of the 2-year period. A group of 56 healthy age-matched volunteers were used as controls. Eighteen patients had severe or multiple infections during the study period, 11 patients had recurrent infections and the remaining 30 patients had only minimal infections. Overall, serum IgG levels were low in 32 patients but in none of the control group (P = 8.8 x 10(-11). However, less than half of those patients with hypogammaglobulinaemia suffered from severe or multiple infections. Specific antibodies to pneumococcal capsular polysaccharide were low in 23 patients compared with six of the control group (P = 4.9 x 10(-4)). The majority of patients with severe or multiple infections (13/18) had low levels of both total IgG and specific antibodies to pneumococcal capsular polysaccharide. However, in the groups of patients with less frequent infections, a higher proportion had low serum IgG than low pneumococcal antibody levels. Low levels of pneumococcal antibodies were particularly associated with severe or multiple infections (P = less than 0.00001). PMID- 1516255 TI - The macrophage response to bacteria. Modulation of macrophage functional activity by peptidoglycan from Moraxella (Branhamella) catarrhalis. AB - Moraxella (Branhamella) catarrhalis organisms have been shown to be particularly efficient in inducing in a pure population of bone marrow-derived mononuclear phagocytes secretory and cellular activities. In the present study, the ability of peptidoglycan from this Gram-negative organism to trigger a macrophage response was compared with that elicited by peptidoglycan from Staphylococcus aureus and Bacillus subtilis. The results show that the three peptidoglycans were similarly active in triggering the secretion of tumour necrosis factor and tumouricidal activity but differed considerably in their ability to induce the generation of nitrite in macrophages; in this respect, peptidoglycan from M. catarrhalis was particularly potent. The impressive capacity of M. catarrhalis peptidoglycan to induce in low concentration the secretion of tumour necrosis factor and nitrite and tumouricidal activity may, in addition to its lipopolysaccharide, contribute to the extraordinary potential of this organism to trigger the functional activities of macrophages. PMID- 1516256 TI - The pattern of mycobacterial antigen recognition in sera from Mantoux-negative individuals is essentially unaffected by bacille Calmette-Guerin (BCG) vaccination in either south India or London. AB - Paired sera were obtained before and 8 weeks after routine BCG vaccination from 20 PPD-S Mantoux-negative individuals who were living adjacent to the Chingleput BCG vaccine trial area in Tamil Nadu and from seven Mantoux-negative school children in London, UK. Most subjects became Mantoux-positive after vaccination. In ELISA tests against soluble extracts of BCG or Mycobacterium tuberculosis H37Rv or against PPD-S, pre-vaccination antibody titres of South Indian subjects were about twice those of British subjects but there was no increase in titre of antibodies after vaccination of either population. Western blotting showed that even before vaccination, and even in British subjects, antibodies were present that recognized numerous antigenic components in extracts of BCG and M. tuberculosis. There was no consistent difference between band patterns with South Indian and British subjects and any effect of vaccination on the patterns was minimal. PMID- 1516258 TI - Prevalence of anti-Fab antibodies in patients with autoimmune and infectious diseases. AB - Sensitive ELISA were devised to examine the specificity of circulating IgM and IgA autoantibodies for whole human IgG, Fc and Fab fragments of human IgG. Sera from patients with autoimmune and infectious conditions such as rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), tuberculosis (TB), infectious mononucleosis (IM) and cystic fibrosis (CF) were studied. Results of the ELISA assays using whole human IgG as antigen revealed that a proportion of patients in each of the groups studied had circulating IgM and IgA rheumatoid factors (RF). Fifteen normal individuals studied were negative. In the latex positive RA group, IgM RF and IgA RF had primarily anti-Fc reactivity (100% and 93% respectively), although 3/15 patients also showed IgM anti-Fab reactivity and one patient had high IgA anti-Fab activity. Patients with SLE and TB who had detectable RF levels also revealed predominantly anti-Fc specificity. In contrast, examination of 25 patients with IM showed positivity for IgM RF activity in 8% of patients using whole IgG as antigen, 24% positivity using purified Fc fragments as antigen and 45% positivity when plates were coated with Fab fragments. Similarly, a large number of CF patients (54%) also showed predominantly IgM anti-Fab activity. Of interest, 69% of the CF patients who were all studied at the time of bacterial infection had detectable IgA RF levels, with 46% of these patients showing both IgA anti-Fc and anti-Fab activity. These findings suggest that autoantibody specificities in autoimmune and infectious diseases are different. PMID- 1516257 TI - Ivermectin-facilitated immunity in onchocerciasis. Reversal of lymphocytopenia, cellular anergy and deficient cytokine production after single treatment. AB - A longitudinal investigation has been conducted into the cell-mediated immune responses of onchocerciasis patients after a single-dose treatment with ivermectin. Untreated patients tested for delayed cutaneous hypersensitivity (DCH) to seven recall antigens showed lower responses than infection-free control individuals (P less than 0.01), but 6 and 14 months after treatment DCH reactions increased to similar levels to those seen in the controls. The in vitro cellular reactivity to Onchocerca volvulus-derived antigen (OvAg) was reduced in untreated patients as compared with controls, and the lymphocyte blastogenic responses to OvAg and streptolysin-O clearly improved up to 14 months after treatment. Peripheral blood mononuclear cells (PBMC) from untreated patients produced IL-1 beta, tumour necrosis factor-alpha (TNF-alpha) and IL-6 in response to mitogenic stimulation with phytohaemagglutinin (PHA), only low levels of IL-1 beta, IL-2 and TNF-alpha in response to OvAg, but higher amounts of IL-4 and interferon gamma (IFN-gamma) in response to OvAg than control individuals. After ivermectin treatment, the OvAg-induced production of IL-1 beta and TNF-alpha increased significantly 1 and 14 months after treatment. The PHA-induced production of IL-2 and IL-4 increased 1 month after treatment and remained significantly elevated until 14 months after treatment, whereas the OvAg-specific secretion of IL-2, IL 4 and IFN-gamma did not change after ivermectin treatment. Flow cytometric analysis of lymphocyte-subsets in the peripheral blood of untreated patients revealed a relative and absolute (P less than 0.01) diminution of CD4+ cells and a significantly smaller CD4+/CD8+ cell ratio as compared with controls. By 4 weeks after treatment and thereafter, CD4+ T cells increased relatively and absolutely (P less than 0.01); likewise there was an absolute increase in T helper-inducer cells (CD4+CD45RO+) and a temporarily improved CD4+/CD8+ cell ratio (P = 0.001). The expression of the low-affinity receptor for IgE (CD23) on total lymphocytes decreased from 14% to 7% by 14 months after treatment. The CD8+ cells and CD3+TCR gamma delta + cells were higher in patients than in controls and both remained elevated until 14 months after treatment. These results suggest a distinctly improved cellular immunity in human onchocerciasis that was facilitated by ivermectin therapy. PMID- 1516259 TI - Agalactosyl IgG in pristane-induced arthritis. Pregnancy affects the incidence and severity of arthritis and the glycosylation status of IgG. AB - The effect of pregnancy on the incidence and severity of pristane-induced arthritis was examined along with the glycosylation status of IgG during the ante natal and post-partum periods. It was found that pristane-induced arthritis is prevented by pregnancy. In addition, the levels of agalactosyl IgG fall during pregnancy but rise to greater than normal within a few days of parturition, before resetting towards the norm shortly afterwards. Interestingly, the level of agalactosyl IgG correlates with the severity of arthritis. As previously reported IL-6 may be an important factor, not necessarily the only one, in the production of agalactosyl IgG. Here it is clearly demonstrated that the kinetics of IL-6 activity post-pristane injection parallels the kinetics of agalactosyl IgG production. In addition, the overshoot in agalactosyl IgG levels immediately post partum coincides with a burst in IL-6 activity. It is considered that these changes in IgG glycoform levels, or the factors which control them, may be related to the mechanisms underlying prevention/remission of arthritis during pregnancy. PMID- 1516260 TI - Oestrogen-induced suppression of collagen arthritis; 17 beta-oestradiol is therapeutically active in normal and castrated F1 hybrid mice of both sexes. AB - The F1 hybrid mouse strain, from B10Q and DBA/1 parentals (the QD strain), is highly susceptible to induction of type II collagen-induced arthritis, an experimental model for rheumatoid arthritis. Males are more susceptible than females. Oophorectomy enhances susceptibility to arthritis and treatment with physiological doses of 17 beta-oestradiol (E2) suppresses disease. E2 treatment lowers the incidence of arthritis also in non-castrated and castrated males, showing that the anti-arthritic effect by oestrogen is not dependent on either sex hormone imprinting effects or interference with male sex hormones. Testosterone treatment of normal females, but not of castrated females, exaggerated development of the disease. In the testosterone-treated normal females, the oestrogen effect on vaginal smear was abolished and ovarian weight decreased, suggesting that the testosterone-mediated enhancing effect is caused by inhibition of ovarian oestrogen production. The crucial importance of oestrogens for the development of arthritis is focused on the effectiveness of treatment with gestation-related doses of E2 of normal, non-castrated females. PMID- 1516261 TI - T cell responses to synthetic TSH receptor peptides in Graves' disease. AB - Twenty-eight peptides, representing the entire extracellular domain of the TSH receptor, were synthesised to investigate which parts of this autoantigen may be targets for the T cell response in Graves' disease (GD). T cells from 11 of 21 controls and 26 of 36 newly diagnosed GD patients proliferated in response to one or more peptides with a stimulation index (SI) of greater than 2.0 (chi 2 = 2.31, P greater than 0.1). The response of patients and controls to any of the individual peptides was also not statistically different. However, individual patients gave high SIs with certain peptides to which controls either gave an absent or very weak response. HLA-DR3 was not associated with any particular response to TSHR peptides. Three out of seven GD patients whose T cells were evaluated before and after treatment showed a response of this kind only early in the course of their disease. Intrathyroidal T cells from four GD patients did not give a consistent proliferative response to pools of five peptides, and depleting peripheral blood T cells of their CD8+ population did not affect the proliferative response. These results indicate that the T cell response to the TSH receptor in GD does not seem to be directed against any one particular epitope on the peptides we have tested which cover the extracellular domain. PMID- 1516262 TI - Significance of C3 nephritic factor (C3NeF) in non-hypocomplementaemic serum with membranoproliferative glomerulonephritis (MPGN). AB - C3NeF is an autoantibody of C3 convertase (C3bBb) and is often detected in the serum of hypocomplementaemic MPGN patients. Serum samples from 104 non hypocomplementaemic MPGN patients (C3NeF) were studied. C3NeF, which cannot activate the alternative pathway, was found in the sera of 6 patients. We examined the C3NeF in purified IgG from five of the non-hypocomplementaemic serum samples (non-hypo C3NeF) and four hypocomplementaemic serum samples (hypocomplementaemic C3NeF) to determine why C3NeF does not induce C3 splitting and hypocomplementaemia. Purified IgG from non-hypo C3NeF stabilized EAC4b3bBb cells in a manner similar to IgG from hypocomplementaemic C3NeF in EDTA gelatin veronal buffer. However, the non-hypo C3NeF IgG did not stabilize C3 convertase (EAC4b3bBb cells) in the presence of control proteins (factors H and I), whereas the hypocomplementaemic C3NeF IgG did. The C3NeF in the hypocomplementaemic serum displayed two characteristics: (i) inhibition of intrinsic decay of Ce convertase (C3bBb); and (ii) inhibition of extrinsic decay by factors H and I. Although the C3NeF in the non-hypocomplementaemic sera did inhibit the intrinsic decay in a manner similar to the hypocomplementaemic C3NeF IgG, it did not inhibit the extrinsic decay. Due to the different characteristics of hypocomplementaemic C3NeF and non-hypo C3NeF in the serum samples, the non-hypo C3NeF did not activate C3. Therefore, we conclude that C3NeF exhibits a heterogeneity which is very important in relation to the pathogenesis of MPGN. PMID- 1516263 TI - C7 M/N protein polymorphism typing applied to inherited deficiencies of human complement proteins C6 and C7. AB - C7 M/N typing, the determination of the complement component C7 M/N phenotypes, was successfully used in family studies to trace haplotypes bearing C7 deficiency genes. Furthermore, it was shown to be preferable to C7 allotyping based on isoelectric focusing (IEF) since it distinguishes two common alleles (C7*M and C7*N), whereas one common C7 IEF allele (C7*1) predominates in most populations. It is also the more sensitive method, as it enabled detection of very low amounts of abnormal C7 molecules in the third generation of a combined subtotal C6/C7 deficient subject and thus confirmed that this partial deficiency gene is not silent in heterozygotes. In this respect C7 M/N typing is even more informative than DNA restriction fragment length polymorphism typing which will assess the presence but not necessarily the functional status of a gene. C6 and C7 genes are tightly linked and therefore C7 M/N typing was also applied to tracing C6 deficiency genes in families. C6/C7 haplotype analysis of South African C6 deficient (C6Q0) subjects revealed a strong allelic association of C6*Q0 and C7*M. PMID- 1516264 TI - Soluble forms of membrane cofactor protein (CD46, MCP) are present in plasma, tears, and seminal fluid in normal subjects. AB - We have established an ELISA for determination of membrane cofactor protein (MCP, CD46) both solubilized from cell membranes and released in body fluids. In this assay, mouse MoAbs against MCP, M177 and M160 whose epitopes were different, were used as capture and detection antibodies, respectively. The NP-40 concentration in samples for MCP to be measured must be less than 0.05%. The detection limit of this MCP assay was 0.5 ng. The assay was used to quantify solubilized membrane MCP, and soluble MCP in normal human plasma, serum, urine, saliva, tears, and seminal fluid, and culture media of tumour cell lines. Soluble MCP was barely detected in the conditioned media of the cell lines. The levels of sMCP in plasma and serum were 10-60 ng/ml and that in tears, 0-50 ng/ml. Seminal fluid contained about 10-fold more soluble MCP than serum. Soluble MCP was not detectable by this assay in the other body fluids, suggesting that their MCP levels were less than the detection limit, if any. PMID- 1516265 TI - Abnormal immunoglobulin G subclass production in response to keyhole limpet haemocyanin in atopic patients. AB - A proportion of patients with atopic dermatitis have elevated serum levels of IgG4. In order to investigate further this abnormality of IgG subclass production, atopic patients were immunized with the protein antigen keyhole limpet haemocyanin (KLH), and IgG subclass responses following primary and secondary immunization were analysed. In the primary response, titres of IgG1, 2 and 3 antibodies were lower in the atopic patients than in the controls. In contrast, titres of IgG4 were much higher for the patient group. In both patients and controls, the kinetics of IgG4 antibody production following the initial immunization with KLH showed a slow rise reaching a peak at 30 weeks. This time course indicated that the high IgG4 response was unlikely to be due to previous exposure of the patients to a cross-reacting antigen. A higher proportion of IgG4 was also seen in the atopic patients following secondary immunization; indeed, IgG4 was the major subclass in the secondary response in the patient group. In the controls, but not in the patients, titres of IgG4 anti-KLH correlated with total serum levels of IgG4, and some of the highest IgG4 antibody responses were detected in atopic patients whose serum IgG4 concentration was in the normal range. The results suggest that raised serum levels of IgG4 in atopy may reflect abnormal isotype regulation in response to protein antigens. PMID- 1516266 TI - Standardization: who wants it? PMID- 1516267 TI - Production of reactive nitrogen intermediates by bone marrow-derived macrophages on treatment with cisplatin in vitro. AB - L929 culture medium (a source of macrophage colony stimulating factor (M-CSF) or recombinant granulocyte-macrophage colony stimulating factor (rGM-CSF)-derived bone marrow macrophages treated with cisplatin or lipopolysaccharide (LPS) (10 micrograms/ml) were effective in the production of L-arginine-dependent reactive nitrogen intermediates (RNI) and generation of tumouricidal activity. The abilities of RNI secretion and related tumouricidal activity against P815 mastocytoma cells were compared. These parameters were found to be closely correlated in various experiments. RNI secretion and generation of bone marrow macrophage-mediated tumouricidal activity were significantly inhibited by L-N monomethyl arginine (L-NMMA), a specific inhibitor of the L-arginine pathway, but L-NMMA did not inhibit macrophage-mediated killing of tumour necrosis factor (TNF)-sensitive Wehi cells, suggesting that activated macrophages exhibit at least two cytolytic mechanisms, one by L-arginine-dependent nitric oxide pathway and another by TNF-mediated killing. The present findings suggest that the mechanism of tumour cell killing by activated macrophages may differ, depending on the tumour cell type, and reactive nitrogen intermediates play a major role in cisplatin-mediated activation of bone marrow-derived macrophages. PMID- 1516268 TI - Regulation of proximal tubule function by angiotensin. AB - 1. Independent of its effects on renal haemodynamics and glomerular filtration, angiotensin II (AII) has direct actions on the proximal tubule involving transepithelial Na+, H+, HCO3-, and water reabsorption, ammoniagenesis, gluconeogenesis and renal growth. 2. The effects of AII on water and electrolyte transport are biphasic and dose-dependent, such that low concentrations (10(-12) 10(-9) mol/L) stimulate reabsorption whereas high concentrations (10(-7)-10(-6) mol/L) inhibit reabsorption. Similar dose-response relations have been obtained for luminal and peritubular addition of AII. 3. The cellular responses to AII are mediated via an AT-1 receptor coupled via G-regulatory proteins to several parallel signal transduction pathways. Low doses inhibit the basolateral adenylate cyclase, lower intracellular cAMP and withdraw the inhibitory effect of protein kinase A on the luminal Na/H exchanger. Stimulation of this exchanger may also occur due to AII-receptor activation of phospholipase C to release diacyl glycerol, or by local transduction in the brush-border membrane involving phospholipase A2. 4. Inhibition of proximal fluid reabsorption is associated with increased intracellular Ca2+ released from intracellular stores, or entering via voltage-sensitive channels in response to the release of inositol-1,4,5 trisphosphate, or following Ca2+ channel opening induced by the arachidonic acid metabolite 5,6-epoxy-eicosatrienoic acid. 5. The stimulatory actions of peritubular AII on proximal transport are inhibited by physiological concentrations of atrial natriuretic factor (ANF) and by parathyroid hormone (PTH). 6. It is concluded that intrarenal AII acts to maintain optimal matching of fluid reabsorption and filtered load in response to changes in sodium balance, as well as to promote acidification of the urine during acidosis and perhaps to potentiate tubular growth following renal injury. PMID- 1516269 TI - Failure of the nitrous oxide tissue equilibration method for the determination of brain and myocardial blood flow under controlled conditions. AB - 1. Two adult merino ewes were prepared with intravascular cannule for sampling aortic root blood, sagittal sinus blood and coronary sinus blood. 2. One week after preparation the animals were anaesthetized then ventilated with a gas mixture containing 10% nitrous oxide (N2O) for 60 min. Serial measurements of brain and myocardial blood flow were made using the N2O tissue equilibration method of Kety and Schmidt. 3. N2O failed to achieve matching arteriovenous blood concentration equality and saturation of the relevant tissues. Valid use of the Kety-Schmidt method, therefore, could not be confirmed. 4. Because of the failure of the arteriovenous equilibration, serially determined brain and myocardial blood flows were found to decrease with time. 5. The use of this method in circumstances where tissue saturation with the indicator gas cannot be ascertained is arbitrary. PMID- 1516270 TI - Sodium and noradrenaline in cerebrospinal fluid and blood in salt-sensitive and non-salt-sensitive essential hypertension. AB - 1. The effects of dietary sodium on blood pressure and levels of sodium, other electrolytes and noradrenaline (NA) in the cerebrospinal fluid (CSF) and blood of 15 patients with essential hypertension were studied. The CSF and blood sampling was carried out after 7 days of a high salt intake (16-18 g/day) and after 7 days of a low salt intake (1-3 g/day). 2. Blood pressure and sodium concentrations in CSF and serum were significantly higher in the high salt period than the low salt period (CSF Na+ concentration: 147.7 +/- 0.4 mmol/L vs 145.3 +/- 0.5 mmol/L; P less than 0.001). Levels of CSF pressure and potassium or calcium concentrations were not different between the two periods. Plasma NA and plasma renin activity (PRA) were lower and CSF NA levels tended to be lower in the high salt period. 3. The levels and the changes in sodium and NA in CSF were not significantly different between the salt-sensitive (n = 8) and the non-salt-sensitive (n = 7) subjects, but the changes in plasma NA and PRA were smaller in the salt-sensitive subjects. 4. These results indicate that the sympathetic nervous system is less suppressed in salt-sensitive subjects during high salt intake. This may be due to altered neural responsiveness to sodium loading rather than being greater increases in sodium concentration in the central nervous system. PMID- 1516271 TI - Potassium channel activation improves blood flow pattern of conscious rats in cutaneous microcirculation. AB - 1. A dose-dependent mean arterial blood pressure reduction (tailcuff method) to an intravenously administered potassium channel activator (22 or 24 micrograms/kg bw) was found in conscious rats. 2. Intravital microscopic analysis of skin microcirculation in conscious rats was performed with respect to erythrocyte flow velocity and diameters of capillaries. There was a dose-dependent increase of erythrocyte flow velocity; diameters of capillaries were dilated following a dosage of 6 and 12 micrograms/kg bw, but constricted following a dosage of 24 micrograms/kg bw. 3. Frequency distributions of velocity ranges in capillaries under observation (real time video recordings) proved that the increase of microvascular perfusion is manifested by a shift of maximal values to increasing velocity ranges. 4. It is concluded that potassium channel activation plays an important role in the local regulation of perfusion on the peripheral circulation. PMID- 1516272 TI - Time course of regional flow distribution following reperfusion of the isolated ischaemic rat heart. AB - 1. The regional distribution of flow was studied at different times after the onset of reperfusion in isolated rat heart preparations. The hearts were submitted to 30 min of global ischaemia followed by 60 min of reperfusion. Microspheres labelled with various nuclides were added to the perfusate before ischaemia and 1, 5, 20, and 60 min after the onset of reperfusion. 2. One minute after the start of reperfusion, the flow to the left ventricular inner layer was restricted to 0.5 +/- 0.2 mL/min per g (2-3% of the pre-ischaemic flow). In this segment, the perfusion remained at the same low level during the entire reperfusion period studied. At the onset of reperfusion the flow to the outer layer of the left ventricle was 4.8 +/- 1.7 mL/min per g (37% of the pre ischaemic flow), and 3.0 +/- 1.3 mL/min per g (27% of the pre-ischaemic value) to the free wall of the right ventricle. The flow was progressively reduced in the outer layer of the left ventricle in the course of reperfusion. After 60 min of reperfusion the flow to the left ventricular outer layer was 2.5 +/- 0.9 mL/min per g (19% of pre-ischaemic flow when compared with the onset of reperfusion [P less than 0.05]). 3. It is concluded that a 'no-reflow' condition develops very early during reperfusion and becomes more marked during this period. PMID- 1516273 TI - Isolation and characterization of the rat liver AVP receptor using [125I][d(CH2)5'sarcosine7]AVP. AB - 1. A vasopressin (AVP) binding protein was purified from rat liver membranes by an improved method using [125I][d(CH2)5'Sarcosine7]AVP, a selective V1 AVP radioligand and a combination of CHAPS solubilization, gel filtration, lectin affinity and FPLC ion exchange chromatography. 2. The purified protein exhibited a maximum binding activity of 2480 pmol/mg protein with a KD of 4.5 nmol/L, which corresponds to a purification of approximately 26,700-fold. The molecular weight of this protein was 70,000 Da. 3. The binding of [125I][d(CH2)5'Sarcosine7]AVP to the solubilized membranes was dependent on the protein concentration, and was inhibited by the unlabelled peptides [d(CH2)5'Sarcosine7]AVP, AVP, and to a lesser degree by peptides with high V2 receptor affinity, such as 1-desamino-D AVP and [d(CH2)5'D-Ileu2-Ileu4]AVP. 4. In addition, an AVP anti-idiotypic monoclonal antibody bound to both the partially purified and purified lectin affinity AVP binding protein in a concentration-dependent manner. These results indicate that the purified protein displays similar characteristics to the liver membrane-bound AVP V1 receptor. PMID- 1516274 TI - Increased sensitivity to endothelin-1 in isolated Krebs'-perfused kidneys of streptozotocin-diabetic rats. AB - 1. Vascular responses to endothelin-1 (ET-1) and noradrenaline (NA) were measured in isolated Krebs'-perfused kidneys of 2 week old streptozotocin-diabetic and non diabetic rats. 2. Bolus injections of either ET-1 or NA caused dose-dependent increases in perfusion pressure. Responses to ET-1 (10-60 ng/g kidney), but not to NA (0.001-10 micrograms/g kidney), were significantly potentiated in kidneys of diabetic rats compared with non-diabetics. 3. Indomethacin significantly attenuated responses to NA (0.3-10 micrograms/g kidney) in kidneys of both diabetic and non-diabetic rats. 4. Neither indomethacin (1 mumol/L) nor the cyclo oxygenase/lipoxygenase inhibitor BW755C (1 mumol/L) had any significant effect on the log dose-response curve to ET-1 in either group of kidneys. 5. Perfusion with N-nitro-L-arginine (NOLA; 10 mumol/L) had no effect on basal perfusion pressures, but potentiated responses to ET-1 in both groups of kidneys. However, the difference in responses to ET-1 between kidneys from diabetic and non-diabetic rats remained significant in the presence of NOLA. 6. ET-1 responses were inhibited in Ca(2+)-free Krebs' solution (plus 1 mmol/L EGTA). 7. The results of the present study indicate an increased sensitivity to ET-1 in isolated Krebs' perfused kidneys of diabetic rats. Responses to ET-1 were unaffected by cyclo oxygenase and/or lipoxygenase inhibitors, but were potentiated by an endothelium derived relaxing factor (EDRF) synthesis inhibitor. PMID- 1516275 TI - Measurement and identification of prorenin and renin in ovarian follicular fluid from cattle and pig. AB - 1. In previous studies we have demonstrated and solved several methodological problems in relation to the measurement of prorenin by trypsin activation in rat, bovine, hog and horse plasma. 2. The aim of the present study was to develop a method for the measurement of prorenin in bovine and porcine ovarian follicular fluid. 3. Trypsin activation of follicular fluid generated angiotensin I immunoreactive material (AI IM) in both species. 4. The AI IM interfered with the renin assay, but could be completely removed by a cation exchange resin in a batch-wise technique. 5. The enzymatic activity of trypsin-activated prorenin and pre-existing active renin was completely inhibited by a specific inhibitor of renin. 6. The reactions were optimized and an accurate measurement of prorenin in ovarian follicular fluid was developed. 7. The existence of prorenin and renin in bovine ovarian follicular fluid was established. Prorenin and renin in porcine ovarian follicular fluid was demonstrated for the first time. 8. The ratio between ovarian follicular fluid and plasma was 43 for prorenin and 19 for active renin in cattle. The same ratios in pigs were 1.3 and 0.4, respectively. These findings indicate a species difference with respect to the amount of prorenin or active renin present in ovarian follicular fluid. PMID- 1516276 TI - Endothelin response in SHR and WKY. PMID- 1516277 TI - Hematologic parameters and iron stores in patients on hemodialysis for chronic renal failure. AB - Thirty-two patients on hemodialysis for chronic renal failure were investigated. A correlation was sought between bone marrow iron stores assessed on Prussian blue stained smears, and some common hematological parameters such as red blood corpuscle indexes obtained by coulter counter, serum iron, iron-binding capacity and serum ferritin levels (measured by RIA). MCH and MCV were both found significantly depressed in patients with depleted iron stores, a situation not reflected by any of the other tested parameters. These results reveal a practical and simple guideline for the treating practitioner who wants to initiate iron supplementation or withdrawal in these patients especially in areas where more elaborate tests may not be at hand. PMID- 1516278 TI - Primary hypothyroidism and multiple endocrine failure in association with hemochromatosis in a long-term hemodialysis patient. AB - A 56-year-old male patient on chronic hemodialysis developed liver cirrhosis. He received a total of 20 liters of blood transfusion. Bronze pigmentation of the skin and iron deposition to the liver, spleen, pancreas and thyroid gland, which was demonstrated by computed tomography and magnetic resonance imaging studies, and histological demonstration of iron deposition to the thyroid gland, bone marrow and gastric mucosa established a diagnosis of secondary hemochromatosis. Endocrine work-up revealed the presence of diabetes mellitus with minimum insulin secretory response, primary (or thyroprivic) hypothyroidism, hypoparathyroidism and hypogonadotropic hypogonadism. A wide-spread endocrine involvement as seen in this patient is a rare clinical feature of hemochromatosis secondary to massive blood transfusion in hemodialysis patients. Particularly, primary hypothyroidism due to iron deposition to the thyroid gland was quite a rare feature of hemochromatosis. PMID- 1516279 TI - Clearance of 131I by hemodialysis. AB - There are no available data documenting the dialysis clearance of iodide in humans. This work quantitates the hemodialysis clearance of iodide (as 131I) over time and examines certain factors which influence that clearance. In a single patient study, three dialysis periods were studied over the 24 to 96 hours following administration of 129 mCi 131I given as Na131I. Hemodialysis clearance of 131I was calculated both from the arterio-venous difference of 131I across the artificial kidney and the appearance of 131I in the expended dialysate. Calculations were based on 131I activity in whole blood, whole plasma, and the supernate of plasma treated with 10% trichloroacetic acid (TCA). The hemodialysis clearance of 131I was highest when calculated from the activity of the plasma supernate, 171.3 +/- 6.0 ml/min for the period 24-29 h. post dosing, and fell in a linear fashion with time. The clearance calculated from whole blood activity was always intermediate to that from whole plasma (lowest) or the plasma supernate (highest). The percentage of plasma 131I activity precipitated by TCA rose over the study period and displayed a strong negative correlation to the hemodialysis clearance of 131I. The hemodialysis clearance of iodide, as 131I, is on the order expected for a free ion and is 4-5 times higher than the endogenous renal clearance of the ion. However, the calculated clearance varies with respect to total time of dialysis and the fraction of blood in which the 131I activity is measured.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1516280 TI - Microangiopathic hypothesis of POEMS tissue lesions. PMID- 1516281 TI - IgA nephritis in HIV-positive patients: a new HIV-associated nephropathy? AB - Four HIV-positive patients were shown to have IgA-associated nephritis on biopsy, including one with anaphylactoid purpura. Three were homosexuals, while the fourth acquired the infection from his mother. All had hematuria, a variable degree of proteinuria and renal disease with a benign course. Serologic studies showed elevated levels of IgA as well as IgA immune complexes and rheumatoid factor. IgA antibodies to multiple HIV antigens were detected by Western blot. Pathologic studies showed tubuloreticular inclusions in endothelial cells and nuclear bodies in interstitial cells in all cases. HIV antigens were not detected in kidney biopsies by monoclonal antibodies nor was HIV viral genome demonstrated by in situ hybridization. The possibility that this represents a unique type of IgA-associated HIV nephropathy is discussed. PMID- 1516282 TI - Incidence of microalbuminuria in ambulatory patients with acquired immunodeficiency syndrome. AB - Nephropathies associated with human immunodeficiency syndrome (HIVAN) are characterized by gross proteinuria, lack of change in blood pressure, and various histologic lesions. The present study prospectively measured microalbuminuria in 72 HIV-seropositive patients (3 asymptomatic, 32 AIDS-related complex, 37 AIDS) screened for Phase I clinical pharmacology studies. There were 14 patients (19.4%) that had abnormal urinary levels of microalbumin; 7 of these patients (50%) had proteinuria similar to those values found in diabetic nephrotic syndrome. Microalbumin levels were not correlated with race, sex, risk factors of AIDS, disease history, or concurrent drug therapy. In contrast, urinary microalbumin levels were correlated with CD 4 T-cell and WBC counts, tumor necrosis factor alpha and beta 2-microglobulin levels, suggesting an association between AIDS progression and microalbuminuria. By monitoring urinary microalbumin levels, those patients susceptible to the development of nephrotic syndrome could be identified and prophylactic measures initiated. PMID- 1516283 TI - Two-color analysis of lymphocyte subpopulations in patients with nephrotic syndrome due to membranous nephropathy. AB - Two-color flow cytometry was carried out to determine the correlation between cell-mediated immunity and the levels of proteinuria in 30 patients with membranous nephropathy. Lymphocyte subpopulations were measured by two-color flow cytometry using various monoclonal antibodies of the Leu series. Clinically, the patients were divided into four stages as follows: 1. untreated nephrotic stage, 2. prednisolone (PSL) treated nephrotic stage, 3. persistent proteinuric stage (incomplete remission, ICR) and 4. complete remission (CR). Two-color flow cytometry showed a significant decrease in Leu 2a+15+ (suppressor T) cells and relative increase in Leu 3a+8+ (suppressor inducer T) cells in the untreated nephrotic stage. The mean Leu 3a+8-/Leu 2a+15+ (helper/suppressor) cell ratio was normalized in the persistent proteinuric stage or complete remission after treatment with PSL. Patients with membranous nephropathy showed a significant elevation of Leu 2a+DR+ cells after treatment with PSL. The abnormalities of suppressor T cells and suppressor inducer T cells in the peripheral blood appear to reflect the levels of proteinuria in patients with membranous nephropathy. It was concluded that PSL might stimulate Leu 2a positive cells and then increase the number of Leu 2a+15+ cells in the peripheral blood of patients with membranous nephropathy. PMID- 1516284 TI - Chronic dialysis in patients with systemic amyloidosis: the experience in northern Italy. AB - The clinical outcome of 61 patients with renal amyloidosis treated with chronic dialysis was reviewed. Eighteen patients, 4 with primary or AL amyloidosis and 14 with reactive or AA amyloidosis, died within one month from starting treatment. The other 43 patients were treated with dialysis for 3 to 199 months and are the object of this study. Sixteen patients had AL amyloidosis and 27 had AA amyloidosis. Thirty-five patients were treated with hemodialysis (HD) for a mean period of 40 +/- 47 months and 8 were treated with continuous ambulatory peritoneal dialysis (CAPD) for 20 +/- 15 months. Patient survival rate at 1 and 5 years was 68% and 30% respectively. There was no difference in survival rate between patients treated with HD and those treated with CAPD, while patients younger than 45 had a better 5-year survival rate. Twenty four (60%) patients achieved a satisfactory rehabilitation with dialysis. At the last follow-up, 15 patients (14 on HD, 1 on CAPD) were alive 61 +/- 58 months after starting dialysis. Twenty-eight patients died after 30 +/- 20 months. The main causes of death were: cardiovascular accident (11), stroke (3), sepsis (5) and cachexia (5). The most important extra-renal complications of amyloidosis were related to cardiovascular involvement (heart failures, arrhythmias, hypotension) and gastrointestinal involvement (malabsorption). Intra-dialytic hypotension in patients on HD and peritonitis in patients on CAPD were the main problems related to dialytic procedure. his study confirms that life expectancy and the quality of life of dialysis patients with systemic amyloidosis are poorer than those of general dialysis population.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1516285 TI - Heparin-induced thrombocytopenia in renal failure. AB - A 35-year-old patient with symptomatic chronic renal failure secondary to hereditary nephritis underwent heparinization during urgent hemodialysis. Subclavian catheter insertion was complicated by staphylococcal septicemia which precluded Gore-tex graft placement. Arteriovenous fistula failed immediately postoperatively and thrombectomy was required. Heparin-induced thrombocytopenia was suspected and the test was strongly positive. Acetyl salicylic acid (ASA) 40 mg, was used with heparin for dialysis, and there were no episodes of gastrointestinal hemorrhage or access site thrombosis. The use of very low-dose ASA in this setting is reported. PMID- 1516286 TI - Serum and urinary ceruloplasmin in experimental nephrotic syndrome. AB - The levels of ceruloplasmin (Cp) and total protein were measured in serum and urine from rats with experimental nephrotic syndrome (NS) for 20 days after a single injection of puromycin aminonucleoside (PAN). Control values for Cp in serum and urine were: 0.23 +/- 0.01 mg/ml and 0.063 mg/day, and those for total protein were: 7.1 +/- 0.14 g/dl and 2.1 +/- 0.6 mg/day, respectively. It was found that: a) serum Cp decreased on day 6, remained low until day 10 (0.07 +/- 0.01 to 0.08 +/- 0.01 mg/ml), and returned to control levels on day 12; b) total serum protein decreased on day 4, reached the lowest value on day 6 (3.3 +/- 0.3 g/dl) and returned to control levels on day 16; c) Cp in urine increased on day 6, reached a peak value on day 8 (0.62 +/- 0.07 mg/day), then decreased but remained high on day 20; and d) total protein in urine increased on day 5, reached a peak value on day 10 (692 +/- 59 mg/day) and returned to control values on day 20. There was a close association between the levels of Cp and total protein in serum and urine. The decrease of circulating Cp indicates that a typical acute phase response does not occur in the PAN-nephrotic rats. The loss of Cp in the urine of the nephrotic rats may contribute to the decrease in the serum levels of this protein. PMID- 1516287 TI - The effect of cigarette smoking on lymphocyte subsets and progression to AIDS in a cohort of homosexual men. AB - We investigated the effect of cigarette smoking on the percentage of CD4 and CD8 cells (CD4%, CD8%) within a prospective study of homosexual men in Vancouver, Canada and compared progression rates to AIDS among seroincident smokers and non smokers. Serial measurements of CD4% and CD8% obtained from four annual visits were available for 299 men and were compared with respect to smoking status and serologic group. CD4% was significantly elevated (p less than 0.025) and CD8% was significantly lower (p less than 0.002) in seronegative smokers compared to non smokers. However, no effect of smoking was observed in the seropositive group for either of these variables. In a prospective analysis of 122 seroincident subjects, we failed to find a significant association between smoking and progression to AIDS (p = 0.829) or Pneumocystis carinii pneumonia (p = 0.894). At 72 months, cumulative AIDS progression was 29.1% in seroincident smokers compared to 25.2% in seroincident non-smokers. These data suggest that in the absence of HIV, smoking is associated with higher CD4% and lower CD8% but these effects are not present in seropositive subjects with longer durations of infection. Cigarette smoking does not appear to be associated with an altered rate of progression to AIDS. PMID- 1516288 TI - The clinical utility of serum lactate dehydrogenase in diagnosing pneumocystis carinii pneumonia among hospitalized AIDS patients. AB - It has been previously demonstrated that serum lactate dehydrogenase is elevated among HIV patients with pneumocystis carinii pneumonia (PCP). To evaluate the clinical utility of this test we analyzed the admission LDH levels of patients hospitalized for the first time due to the secondary complications of AIDS. Among 76 patients without a prior history of PCP, 41 (54%) had PCP diagnosed during their hospitalization while 35 (46%) did not have PCP. Serum LDH was significantly higher among PCP patients than in patients without PCP (mean = 423 IU/L vs 234 IU/L). Receiver operating characteristic curve analysis demonstrated that at an optimal cutoff point of LDH greater than or equal to 240 IU/L, the test sensitivity and specificity were 0.78 and 0.74 respectively among all hospitalized patients. However, when only patients with dyspnea were considered, the optimal test sensitivity and specificity improved to 0.94 and 0.78 at a cutoff point of LDH greater than or equal to 220 IU/L. Comparing the areas under fitted ROC curves, serum LDH was a significantly better discriminator among patients with dyspnea than among those who were not short of breath. We conclude that while serum LDH is strongly associated with the presence of PCP among AIDS patients, it is a poor screening test for PCP when applied to all hospitalized AIDS patients with and without respiratory complaints. Serum LDH is no substitute for appropriate microbiological studies. However, with further evaluation, it may prove to be a useful test in guiding the clinical management of dyspneic patients in whom sputum or bronchial examinations are negative or not immediately available. PMID- 1516289 TI - A new bioactive molecule for improving vascular graft patency: exploratory trials in dogs. AB - Myxalin is a new bioactive molecule that we have isolated from the culture medium of Myxococcus xanthus, a non-pathogenic Gram negative bacterium. This glycopeptide possesses an antithrombotic effect in vivo and has been shown to promote human endothelial cell growth in vitro. With the object of exploring its ability to improve vascular graft healing and patency, myxalin was immobilized on 6 mm diameter knitted polyester prostheses using gelatin as a carrier, and the prosthesis was then implanted as an infrarenal abdominal arterial substitute in dogs for a period of 2 weeks. Two additional series of implantations were conducted for control purposes: one with gelatin-coated prostheses without myxalin, the other following normal preclotting of the polyester grafts. In order to select adequate sterilization conditions which can preserve the biological activity of myxalin, the prostheses were sterilized according to 3 different sterilization processes (gamma radiation and ethylene oxide either at 63 degrees C or 37 degrees C). At the sacrifice, all grafts were patent. The myxalin treated prostheses exhibited improved blood compatibility in terms of fewer thrombotic deposits and significant inhibition of platelet and fibrinogen uptake on their luminal surfaces. In addition, the development of a thin collagenous internal capsule with endothelial cells secreting high levels of prostacyclin was observed at both anastomoses of the myxalin-treated grafts sterilized by gamma radiation. PMID- 1516290 TI - How many persons in Canada have been infected with human immunodeficiency virus? An exploration using backcalculation methods. AB - We have used the technique of backcalculation to estimate the number of persons in Canada who have been infected with human immunodeficiency virus type 1 (HIV) as of July 1989. We first corrected national AIDS surveillance data in Canada for reporting delay and for underreporting. We then used standard Weibull natural history models as well as an alternative progression model in which the hazard of AIDS was dampened in keeping with observed data from large cohorts. Maximum likelihood techniques were then used to derive the infection curve most consistent with these data. Our best estimate based on this alternative progression model, an underreporting rate of 20%, and a logistic infection curve, was that approximately 29,000 persons in Canada had ever had HIV infection as of July 1989. In a sensitivity analysis utilizing less likely assumptions, the estimates ranged from 17,243 to 48,277. Restricting the same backcalculation process to females under the same assumptions, we estimated that approximately 2,900 females in Canada had ever had HIV infection as of July 1989. The best fitting step function infection curve in females appears to be continuing to rise. Given these estimates, it follows that approximately one in ten infected persons in Canada is female. However, females have only accounted for about one in seventeen AIDS cases. These data are in accord with the widespread impression that transmission of HIV to women has occurred more recently and is on the rise across Canada. The current estimate is lower than previous estimates which placed the number of infected Canadians in the 50,000 to 100,000 range. This lowering should not be taken to mean the situation is improving; rather, the early estimates were simply too high having been based on inadequate data and a rudimentary understanding of the natural history of HIV. Backcalculation is an excellent technique for modelling the incidence of HIV infection several years in the past, but it is not reliable for the most recent few years. A significant increase in HIV infection rates may have occurred in the past few years and it would be beyond the capacity of backcalculation to detect. Backcalculation and unlinked cross-sectional specimen surveys together have the potential to provide an effective means of monitoring the HIV epidemic. PMID- 1516291 TI - Seminal plasma gamma-aminobutyric acid (GABA) levels in normospermic men. AB - Serum and seminal gamma aminobutyric (GABA) concentrations were documented in 10 healthy volunteers. Mean (+/- S.E.M.) GABA concentrations were 0.39 +/- 0.03 microM in serum and 103.3 +/- 28.2 microM in seminal fluid. These differences are in keeping with data reported for the rat and rabbit. A regulatory role for GABA in the reproductive tract is postulated. PMID- 1516292 TI - High protein diet complements resin therapy of familial hypercholesterolemia. AB - The intermediate-term effects on plasma lipoprotein lipids of substituting meat and dairy protein for carbohydrate in the diets of five subjects (three women, two men) with familial hypercholesterolemia receiving cholestyramine (mean dose, 18 g/d) were studied. Subjects were randomly allocated to either the high or low protein diets (mean 27 versus 10% of energy as protein, 25% as fat, and 48 versus 65% as carbohydrate) for 4 to 5 weeks and then switched to the other diet for another 4 to 5 weeks. Mean fasting plasma HDL cholesterol rose significantly by 17 +/- 3% (1.11 +/- 0.12 vs 0.95 +/- 0.11 mmol/L, p less than 0.005, n = 5), whereas total triglycerides fell by 23 +/- 2% (1.7 +/- 0.3 vs 2.2 +/- 0.3 mmol/L, p less than 0.005, n = 5), VLDL triglycerides fell by 28 +/- 5% (0.88 +/- 0.15 vs 1.18 +/- 0.19 mmol/L, p less than 0.02, n = 5), VLDL cholesterol fell by 32 +/- 7% (0.39 +/- 0.08 vs 0.56 +/- 0.09 mmol/L, p less than 0.01, n = 5), the ratio of LDL cholesterol: HDL cholesterol by 19 +/- 5% (4.7 +/- 0.7 vs 5.7 +/- 0.7, p less than 0.05) and that of total cholesterol: HDL cholesterol by 16 +/- 5% (6.6 +/- 0.5 vs 8.0 +/- 0.7, p less than 0.05) on the high versus low protein diet. Increasing dietary protein intake at the expense of carbohydrate may be useful in treating hypoalphalipoproteinemia and/or hypertriglyceridemia in patients with familial hypercholesterolemia. PMID- 1516293 TI - Hyperresponsiveness of sympathoadrenal system in conscious DOCA-NaCl and SHR rats in response to acute hemorrhagic hypotension. AB - The sympathoadrenal basal tone and reactivity were evaluated by the measure of plasma norepinephrine (NE) and epinephrine (EPI) levels in chronically cannulated awake and unrestrained animals under basal conditions and following an acute withdrawal of blood volume necessary to decrease the mean arterial pressure (MAP) by 50 mmHg in normotensive, in deoxycorticosterone acetate (DOCA) and salt (NaCl) hypertensive and in spontaneously hypertensive (SHR) (10-11 weeks) rats. In DOCA NaCl and SHR rats the basal sympathoadrenal tone was found to be increased as was reflected by the higher plasma levels of both catecholamines. Moreover, an enhanced reactivity of the sympathoadrenal system was also observed in DOCA-NaCl hypertensive rats as well as a slight sympathetic hyperreactivity in SHR in response to the hemorrhagic hypotension suggesting the possibility of alterations in the baroreflex functions or in the local modulatory mechanisms. In addition, the acute hemorrhagic hypotension triggered compensatory mechanisms which permitted a rapid return of the MAP to the baseline values in normotensive rats and in the SHR. However, in DOCA-NaCl hypertensive rats, the return of the MAP was delayed and remained below initial levels even 60 min after the hemorrhagic hypotension, suggesting a less efficient compensatory mechanism in these animals despite a markedly potentiated sympathoadrenal response. To explain such a discrepancy, it may be hypothesized that the potentiated sympathoadrenal reactivity could induce a decrease in vascular reactivity by an acute desensitization of the vascular alpha-adrenoceptors in DOCA-NaCl hypertensive rats. PMID- 1516294 TI - Psoriatic spondyloarthropathy in men and women: a clinical, radiographic, and HLA study. AB - Psoriatic spondyloarthropathy as defined by the presence of inflammatory back pain and stiffness, sacroiliitis on physical examination, radiographic evidence of grade greater than or equal to 2 sacroiliitis, and classical or paramarginal syndesmophytes on spinal radiographs was identified in 82 women and 112 men followed at the Psoriatic Arthritis Clinic according to a standard protocol. A logistic regression analysis was performed to look for variables which discriminate between men and women with this condition. No differences in type of peripheral arthritis, degree of damage, or medication were noted between the two groups. However, there was some evidence for more advanced spondyloarthropathy in men. There were no differences in the frequency of HLA B27 or any of the psoriatic arthritis-related HLA antigens. Thus, there may be gender-related differences in the expression of psoriatic spondyloarthropathy, which are unrelated to HLA antigens. PMID- 1516295 TI - Newborn screening for sickle cell and other hemoglobinopathies: a Canadian pilot study. AB - We estimated incidence of HbS disease in Quebec. It is approximately 9 cases per 100,000 births (equivalent to the incidence of the hyperphenylalanemias). Accordingly, we performed a voluntary pilot study in 9 self-identified ethnic groups; 3528 families were counselled about the relevance of newborn screening for hemoglobinopathies; and 2779 cord blood samples were collected (participation rate, 78.7%) and analyzed for Hemoglobin S and other hemoglobin variants by cellulose acetate electrophoresis. There were 95 (3.42%) positive tests on the initial (cord blood) samples, of which only 40 could be confirmed because of low participation in follow-up. We identified 8 false-positive tests; 7 had been classified initially as alpha-thalassemia trait and one as HbC heterozygosity on the first test. The relative frequency of hemoglobinopathy genes (confirmed) was: 52.5% HbS; 22.5% alpha-thalassemia; 22.5% other mutation; all but one patient with sickle cell disease were heterozygotes; the majority (71%) of HbS genes were accounted for by the 7% of screened newborns who were Black; a further 24% of the HbS genes were accounted for by 7% with Central American ancestry. Record linkage of the findings in heterozygotes for use later in life is an unsolved problem. Seventy five first-degree relatives of the 48 probands were screened in follow-up studies (64% of parents participated); 5 couples at risk for having a future child with a hemoglobinopathy were identified. Attitudes toward follow-up varied among the ethnic groups. The single family with an affected newborn (sickle cell anemia) was counselled effectively; the infant received penicillin prophylaxis.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1516296 TI - Pregnancy outcome and infant development following gestational cocaine use by social cocaine users in Toronto, Canada. AB - To determine the effect of first trimester cocaine use on pregnancy outcome we conducted a prospective cohort study of 30 women admitting to social cocaine use (SCU) during early pregnancy, 20 users of cannabis during the first trimester and 30 matched recreational drug-free control subjects. The groups were of similar age, marital status, and obstetric history and were predominantly white. They were of similar socioeconomic status (SES), however the spouses of the cocaine users were of significantly lower SES than those of both control groups (p less than 0.005). The number of years of education of the cocaine users and the fathers of the SCU-exposed fetuses was significantly lower than that of the recreational drug-free control subjects (p = 0.004), however, female IQ was similar among the three groups (109.1 +/- 12.4 cocaine; 109.1 +/- 25.2 cannabis; 114.1 +/- 11.7 drug-free). Alcohol and cigarette use was greater among the cocaine users than among subjects of the recreational drug-free control group (p less than 0.025). Cocaine and the associated lifestyle were not associated with any adverse obstetric or neonatal endpoint (pregnancy weight gain, incidence of delivery complications, gestational age, birth weight, Apgar scores, and rates of major and minor malformations). There were no differences between groups in attaining developmental milestones. Mental and motor scores on the Bayley Scales of Infant Development and Vineland Adaptive Behavior Scales were identical among the three groups, studied at a mean of 19.7 months of age. We conclude that outcome of pregnancy of social cocaine users and subsequent infant physical and cognitive development are within normal limits at 1.6 years of age. PMID- 1516298 TI - Alumina ceramic arthroplasty. PMID- 1516297 TI - Methionine auxotrophy in inborn errors of cobalamin metabolism. AB - Several of the inborn errors of vitamin B12 (cobalamin, Cbl) metabolism (cblC, cblD, cblE, cblF, cblG) are associated with homocystinuria and hypomethioninemia due to a functional deficiency of the cytoplasmic enzyme methionine synthase which requires methylcobalamin (MeCbl) as a cofactor. We compared the growth of cultured fibroblasts from controls, from patients with a selective deficiency of MeCbl (cblE and cblG), with those with a defect in both MeCbl and adenosylcobalamin (AdoCbl) (cblC, cblD and cblF), in methionine and folic acid free media to their growth in fully supplemented medium. Control cells were able to grow in deficient medium supplied with homocysteine, cobalamin and folate, while mutant cells were not, due to their inability to synthesize methionine from its immediate metabolic precursor, homocysteine. This differential growth is useful in screening for genetic defects of methionine biosynthesis. PMID- 1516299 TI - Biocompatibility of surgical-grade dense polycrystalline alumina. AB - This article reviews the knowledge about biocompatibility of alumina since its introduction as a material for use in joint replacements. Alumina is a hydrophilic material with high wettability allowing very low friction with negligible wear. Macrophages loaded with alumina particles show no morphologic alteration and do not lose their chemotactic ability. The host response has been studied for bulk and particulate alumina in soft tissues, as well as in human and animal bone under loaded and nonloaded conditions. The soft-tissue response to bulk alumina exhibits minimal fibrosis, and direct bone contact is achieved at compression-loaded interfaces. Examination of human biopsies from failed total hip prostheses reveals a foreign-body reaction containing predominantly macrophages loaded with alumina particles. No lymphocyte or plasma-cell infiltration is observed because of the absence of soluble component release. The amount of necrosis and fibrosis was lower than that associated with metal or polyethylene debris. In summary, alumina exhibits greater bioinertness than all other implant materials currently available for joint replacement. PMID- 1516300 TI - Combination treatment for adhesive capsulitis of the shoulder. AB - Twenty-two patients (23 shoulders) with arthrographically verified adhesive capsulitis of the glenohumeral joint were treated by a combination of distention arthrography, local anesthetics and steroids intraarticularly, and manipulation. The mean duration of the disease at the time of treatment was 14 months, and all patients suffered from disabling pain and stiffness. A rapid improvement was seen after treatment and at four to six weeks: 91% (21/23) of the patients had no or slight pain and 83% (19/23) of the patients had normal, or almost normal, range of motion. The treatment was well tolerated and no complications were recorded. The combination treatment for adhesive capsulitis of the shoulder is safe, yields immediate results, and is cost effective. PMID- 1516301 TI - Ultrasonography of rotator cuff tears. AB - This is a prospective study of ultrasonography of the rotator cuff mechanism as an alternative to arthrography for screening rotator cuff tears. Seventy-two patients (40 men and 32 women) with possible rotator cuff tears were referred for shoulder arthrography. Before arthrography, bilateral shoulder sonography was performed by a technician under the direction of a radiologist. Arthrograms and sonograms were read separately, and a decision as to the absence or presence of a rotator cuff tear was made without knowledge of the results of the other examination. The results showed 90% sensitivity and 91% specificity, with a positive accuracy of 87%, and a negative accuracy of 93%. Ultrasonography of the rotator cuff is a noninvasive, painless, and cost-effective screening method for patients with a suspected rotator cuff tear. PMID- 1516302 TI - Acetabular reconstruction with a threaded prosthesis for failed total hip arthroplasty. AB - The MEC-Ring threaded acetabular component was used in 35 patients for revision of failed cemented hip arthroplasties, and 32 have been observed for two to four years (mean, 2.5 years). With only a short-term follow-up period, 44% of patients have already required revision for failure of the MEC-Ring acetabular component. Patients with especially poor acetabular bone stock that had had structural bone graft had a significantly higher rate of failure. The authors developed a technique of supine oblique roentgenograms that allowed better visualization of the component-bone interface. Eighty-six percent of patients had radiolucencies, and 67% of these were progressive. The presence of progressive radiolucencies, component migration, or both was associated with a higher failure rate. Progressive radiolucencies were also associated with a worse pain score in patients whose arthroplasties have not failed. The MEC-Ring threaded component is not recommended for revision hip arthroplasty, especially in cases with poor acetabular bone stock. PMID- 1516303 TI - A comparison of total hip arthroplasty and hemiarthroplasty for treatment of acute fracture of the femoral neck. AB - One hundred sixty-six acute, nonpathologic displaced femoral neck fractures in elderly patients were treated with either unipolar hemiarthroplasty (122 operations; 77 cemented, 45 uncemented) or total hip arthroplasty (THA) (44 operations; all cemented). The average age, (75.2 years of age in the THA group 76.2 years of age in the hemiarthroplasty group), anesthesia risk classification, in-hospital mortality, early complications, and dislocation rates were comparable in each treatment group. In an average long-term follow-up period of 56 months, pain, walking, and function scores were higher with THA than with cemented or uncemented hemiarthroplasty. Revision rates were 2.2% after THA, versus 7.9% for cemented hemiarthroplasty and 13% for uncemented hemiarthroplasty. Hemiarthroplasty is recommended for the older patient, who may be occasionally active outside of the household. The healthy, active patient, however, may benefit from THA rather than hemiarthroplasty. PMID- 1516304 TI - Evaluation of the learning curve associated with uncemented primary porous-coated anatomic total hip arthroplasty. AB - The results of the first and second groups of 50 consecutive primary, uncemented porous-coated anatomic arthroplasties were analyzed to evaluate the learning curve associated with the procedure. Femoral fit, acetabular cup angle, femoral fracture rate, minimum two-year clinical hip ratings, and clinical symptoms were compared between the two groups. Significant improvement in achieving better femoral canal filling with the prosthesis and lower acetabular cup angle placements was documented in the second 50 cases. Although a definite learning curve in mastering the technique of uncemented total hip arthroplasty was observed, thigh pain rate and clinical ratings were not improved after two years. PMID- 1516305 TI - Heterotopic bone in hip arthroplasties. Cemented versus noncemented. AB - Sixty-six hip arthroplasties in 55 patients were reviewed to specifically study cemented versus noncemented procedures, as related to heterotopic bone formation (HBF). Other factors considered included the type of arthroplasty, surgical approaches, preoperative and postoperative medicines, preoperative predisposing diagnoses, range of motion, and pain. The overall percentage of heterotopic ossification was 64%. There was no significant difference between cemented (67%) and noncemented (55%) procedures. Except for an increased percentage (80%) of ossification after a trochanteric osteotomy, there were no significant differences between the three reviewed surgical approaches. Male osteoarthritics had the highest overall HBF. Eighty percent of patients who previously had developed HBF also did so with a contralateral hip surgery. Surprisingly, all patients with gout (100%) developed HBF. Acetylsalicylic acid used prophylactically for anticoagulation had no significant effect. Resurfacing arthroplasty procedures accounted for half of the severe grades of HBF. A decreased range of motion occurred with more severe grades of HBF. PMID- 1516306 TI - Intrapelvic extraction of a total hip prosthesis. A case report. AB - A 69-year-old man with a total hip prosthesis, recurrent infection, and intrapelvic incarceration of the acetabular components required extraction of a long-stem total hip prosthesis through three incisions. Retroperitoneal intrapelvic extraction of the incarcerated prosthesis was necessary. This approach allowed removal of intrapelvically migrated components and the eradication of the infection. The patient had no signs of infection five years postoperatively. PMID- 1516307 TI - Pulmonary embolism in total hip and knee arthroplasty. Risk factors in patients on warfarin prophylaxis and analysis of the prothrombin time as an indicator of warfarin's prophylactic effect. AB - This study was designed to identify those total arthroplasty patients at high risk for embolism even while on a proven warfarin prophylactic regimen and to identify the measure of anticoagulation that would be most efficacious in the prevention of pulmonary embolism (PE). A series of 2348 total arthroplasty patients had a preoperative perfusion scan and a postoperative ventilation/perfusion scan. All patients were placed on a low-dose warfarin protocol. Eighty-one patients were identified as having a PE by pulmonary arteriography (incidence of 3.4%). Of these, 89% were asymptomatic and no case was fatal. A control group of 159 patients without PE was used for comparison. Patients older than 65 years of age with a history of genitourinary infection were identified as being at higher risk of PE while on a proven warfarin prophylactic program. These patients may need additional prophylactic measures to reduce the risk of PE. In contrast, patients with a history of phlebitis, PE, obesity, or varicosities were not at excess risk for PE while on warfarin prophylaxis; therefore, no additional prophylactic measures are required. All prothrombin time profiles were within the prophylactic range. Therefore, the actual prothrombin time may not be the critical determinant of the level of anticoagulation or prophylaxis achieved. PMID- 1516308 TI - Separation of the polyethylene liner from acetabular cup metal backing. A report of three cases. AB - In three young patients with cementless Porous Coated Anatomic (PCA) total hip prostheses implanted two to four years previously, the polyethylene liner separated from metal backing. These cups were of the original PCA design, manufactured and packaged as single assembled components, rather than the more recent two-piece components packaged with interchangeable liners separate from the metal backing. Each case of separation was associated with the failure of the thin outer polyethylene rim and central polyethylene peg on the back of the liner that secures it to the metal backing. Cup liners should be securely attached to the metal backing. The possibility of polyethylene failure is considerable when cementless metal-backed acetabular cups are used in active young patients. PMID- 1516309 TI - The modified Insall-Salvati ratio for assessment of patellar height. AB - The Insall-Salvati ratio for the assessment of patellar height was the first widely used index to be relatively independent of knee flexion. Despite the subsequent publication of other indices, it remains the most widely used index. The Insall-Salvati ratio nevertheless has drawbacks, one of which has received little attention: the ratio lacks sensitivity to patellar morphology. Unusual patellar shapes can lead to misleading values of the Install-Salvati ratio. In particular, the authors have found a significant number of inaccurate readings for patellar height in patients whose patella exhibits a long distal (nonarticulating) facet. A modified Insall-Salvati ratio is described which, when applied in conjunction with the traditional ratio, significantly reduces these errors. The cutoff point between normal and alta for this modified Insall-Salvati ratio is 2. One half of the cases of patella alta in this study were missed by the traditional ratio, yet identified by the modified index. PMID- 1516310 TI - A prospective and blinded investigation of magnetic resonance imaging of the knee. Abnormal findings in asymptomatic subjects. AB - To evaluate magnetic resonance imaging (MRI) of meniscal, ligamentous, and bony abnormalities in patients without clinical symptoms, scans were performed on 74 asymptomatic volunteers without histories or symptoms of knee injury. Before review by three radiologists in an independent and blinded fashion, the scans were mixed with 26 MRI scans from symptomatic patients. Sixteen percent of the asymptomatic volunteers had meniscal abnormalities consistent with a tear. The prevalence of MRI findings of a meniscal tear increased from 13% in individuals younger than 45 years of age to 36% in those older than 45. An additional 30% of the volunteers showed meniscal abnormalities consisting of a linear area of increased MR signal not communicating with a meniscal edge, which was not interpreted to represent a tear. The high incidence of abnormal MRI findings in asymptomatic subjects underscores the danger of relying on a diagnostic test without careful correlation with clinical signs and symptoms. These findings also emphasize the importance of access to relevant clinical data when interpreting MRI scans of the knee. PMID- 1516311 TI - A ten- to 15-year follow-up observation of high tibial osteotomy in medial compartment osteoarthrosis. AB - High tibial osteotomy (HTO) was performed on 86 medially osteoarthritic knees in 78 patients. Twelve patients died during the follow-up period. Fifty-six knees of 51 patients were evaluated twice postoperatively: once at six years after surgery and again after ten to 15 years. Results were satisfactory in 88% of the knees at the six-year follow-up evaluation and in 63% at the post-ten-year follow-up evaluation. Ten-year follow-up results significantly deteriorated. The femorotibial angle (FTA) at the time of bone union after HTO was a significant factor that contributed to the ten-year results. In patients maintaining excellent improvement of knee function at the post-ten-year follow-up evaluation, the mean FTA at one year after surgery was 165 degrees; this value was constant through ten years after HTO. An FTA of 164 degrees-168 degrees should be attained to ensure favorable long-term results in HTO. PMID- 1516312 TI - Role of ceramic implants. Design and clinical success with total hip prosthetic ceramic-to-ceramic bearings. AB - Ceramic implants have become of great interest because of the increased awareness that wear debris from metal-polyethylene components of total hip prostheses can cause osteolysis around implants. Polyethylene wear rates with the Charnley total hip prosthesis were found to be from 0.1 to 0.2 mm/year in the elderly, which corresponded to 30 to 80 mm3 of polyethylene debris being released to the joint tissues. This in turn can be related to 40 million to 40 billion particles being released into the joint every year. This polyethylene particulate is heavily implicated in the osteolytic destruction of periarticular tissues. The ceramic ball, ceramic cup combination of total hip prostheses may have promise of wear rates that could be thousands of times smaller than polyethylene alone. Such alumina ceramic prosthetic concepts were introduced in Europe from 1970 to 1973. Under Food and Drug Administration regulations at that time, the only U.S. introductions allowed circa 1980 were the Autophor and Xenophor types of ceramic prostheses. However, this particular prosthetic design was not successful in the United States because of pain, neck-socket impingement, ceramic fracture, and component loosening. This did not therefore appear to be a successful compromise in the hands of U.S. surgeons. Ceramic innovations from Europe now include cemented ceramic cups of "matching" tolerances with the femoral ball, and press fit Ti-alloy acetabular shells with modular ceramic inserts. In addition, alumina and zirconia ceramic balls are now in routine clinical use in Europe. The objectives of this Symposium are to highlight these ceramic ball, ceramic cup innovations with their long-term clinical results from Europe. Then one can evaluate which of these innovations in material and design selections offers the best possible alternatives in the 1990s. PMID- 1516313 TI - Clinical versus instrumented knee testing on autopsy specimens. AB - The accuracy, reliability, and reproducibility of the Genucom Knee Analysis System and Knee Signature System (KSS) for anteroposterior knee laxity evaluations were compared. The devices detected the same relative change in laxity between normal and anterior cruciate ligament-deficient specimens during Lachman and drawer testing; however, the absolute values differed. In a clinical study, two examiners performed three independent Lachman and drawer tests using the Genucom, KSS, and a subjective clinical examination on ten patients. The Genucom demonstrated interexaminer differences during the Lachman test. The clinical examination proved to be more reliable than either instrumented device for both Lachman and drawer testing. The intraexaminer variability of the Genucom and KSS was large, with the average 95% confidence limits about the mean for the Genucom and KSS equal to +/- 4.2 and +/- 2.8 mm, respectively. These findings question the accuracy, reliability, and reproducibility of the instrumented methods. PMID- 1516314 TI - Long-term results of surgical management of Achilles tendinitis in runners. AB - Achilles tendinitis is a common occurrence in long-distance runners. Although most respond well to conservative therapy, there are some who require operative intervention. The short-term results of surgical treatment are good, with a success rate more than 85%. The authors present nine successful long-term results in runners. However, in two of the runners who continued to compete and train at long distances, symptoms recurred. Reoperations were performed to permit successful running careers for five and nine years. Runners resumed their careers after the second operation by supervised training and long-distance, competitive activities. PMID- 1516315 TI - Surgical correction of foot deformities after stroke. AB - Of 104 patients with corrective surgery for foot deformities subsequent to a cerebrovascular accident from 1980 until 1983, 53 patients returned for clinical examination and 22 patients were evaluated by questionnaire and telephone interview. The average follow-up period was 6.4 years. The operative techniques were tenotomy of the toe flexors for hammer-toe deformity, lengthening of the aponeurosis of the gastrocnemius for equinus deformity, and transfer of the anterior tibial tendon or the posterior tibial tendon or the long toe flexors for varus deformity. In 74% of patients, correction was maintained; 79% did not use an orthosis; 51% could bathe unassisted; and 76% were satisfied with the results. The ability to walk was related to the degree of paralysis, the age of the patient at surgery, and the walking speed at discharge. PMID- 1516316 TI - Ipsilateral fractures of the distal radius and scaphoid treated by Herbert screw and external skeletal fixation. A report of two cases. AB - Two patients with comminuted, displaced fractures of the distal radius associated with ipsilateral, undisplaced scaphoid fractures were treated by internal fixation of the scaphoid fracture with a Herbert screw in association with external fixation of the distal radial fracture. One of the patients had a limited open reduction of the distal radius combined with bone grafting. Both patients had satisfactory results. Internal fixation of the scaphoid is indicated if distraction is applied to the carpus to treat an associated fracture of the distal radius, even if the scaphoid fracture is undisplaced. PMID- 1516317 TI - Neurologic deficits in major pelvic injuries. AB - Nerve injury is a common complication of major pelvic injuries. Of 73 patients examined who suffered major pelvic injuries, 24 (33%) had resultant neurologic deficits. The extent of nerve injury is proportionate to the severity of the posterior pelvic bone injury. Sacroiliac dislocation and sacral fractures may be equally complicated by nerve injury. This study suggests that nerve recovery starts three months after injury and stops after two years. Complete recovery was not recorded in severe nerve injuries. Eighty percent of patients recovered from impotence. Nerve injury was found to affect the functional outcome of patients with pelvic injuries. For these reasons, injury should be considered and looked for in every case of pelvic injury. PMID- 1516318 TI - Open reduction of acetabular fracture in pregnancy. A case report. AB - A 24-year-old woman in her 20th week of pregnancy sustained a severely displaced acetabular fracture. Skeletal traction failed to achieve reduction. Open reduction and internal fixation were performed through an extended iliofemoral approach without affecting the pregnancy. At full term, she had a normal delivery. Four years after the injury, the patient had a pain-free hip with full range of motion and a healthy child. The potential benefit or danger of surgery to the patient and her pregnancy was thoroughly considered. PMID- 1516319 TI - Segmental transport after unreamed intramedullary nailing. Preliminary report of a "Monorail" system. AB - The Ilizarov method of segmental bone transport has been shown to be an alternative to more conventional treatments of posttraumatic bony defects. After extensive clinical experience with the unreamed tibial nail in open fractures up to Grade IIIb, a new monorail fixation system for callus distraction and segmental bone transport was devised. This Monorail system is composed of an unreamed intramedullary (IM) nail and a unilateral AO distraction device. The new fixation method and the preliminary clinical experience are reported here. Four patients who previously sustained Grades II-IIIb open tibial fractures had an average bony defect of 9 cm. Two patients had previous bony infections. All patients had had serial debridements and myocutaneous flaps were required in three patients. An unreamed IM nail was inserted, and the transport device was applied. After an osteotomy, segmental transport was carried out until docking was achieved. The external fixator was removed after interlocking of the transported segment. The mean duration of external fixation was 17.9 days/cm and the mean period until roentgenographic consolidation of the distraction and nonunion site was 41.2 days/cm. There were two pin-tract infections but no IM infections. One nail broke after osseous consolidation of the regenerate at the distal interlocking site and required exchange. The goal of transport was achieved in all cases without angular or rotational deformity or length discrepancy. There were no neurovascular injuries. PMID- 1516320 TI - Collagen types. Molecular structure and tissue distribution. AB - The collagens are products of a superfamily of closely related genes. Currently, there are 13 described collagens encompassing at least 25 separate genes. The collagen molecules can be categorized into four classes. Class I consists of molecules that form the banded collagen fibers that are readily seen by routine electron microscopy. The banded fibers are heterogenous with respect to collagen type, containing at least two and often three collagen types in each fibril. This multiplicity is believed to effect the rate of fibril growth and the final fibril diameter. Class II contains collagens that adhere to the surface of the banded fibrils. The function of these molecules is not yet known. The third Class consists of molecules that form independent fiber systems. These include the basement membrane, beaded filaments, anchoring fibrils, and the network surrounding hypertrophic chondrocytes. The last class contains several collagens with unknown fiber forms, and whose functions are unclear. Tissues contain multiple fiber forms and therefore many individual collagen types. Bone is no different, and there are presently four known collagens in the bone cortex. This article summarizes knowledge of the structures and functions of the collagen superfamily. PMID- 1516321 TI - Morphometric and physical investigations of segmental cortical bone autografts and allografts in canine ulnar defects. AB - Cortical bone grafts were implanted for six months in mature dogs using an osteoperiosteal 3-cm defect in the ulna to evaluate their respective morphometric and physical values compared with autografts. The bone-grafting material included fresh auto- and allografts, frozen and thimerosal preserved allografts, and partially demineralized bone allografts. The grafts were evaluated by roentgenograms, microradiograms, photon absorptiometry, porosity, fluorescence labeling measurements, and torsional loading at failure. Autografts achieved a better union score than the allografts, but intracortical bone porosity, percentage of cumulative new bone, and mineral apposition rate were not variables with statistical significance. Lamellar bone was found earlier and in greater quantity in autografts. Within the graft, new bone was deposited at a slower rate than in the recipient bone. Autografts showed less peripheral resorption and a greater torsional resistance than allografts. Photon absorptiometry demonstrated that nondemineralized allografts underwent a substantial loss of peripheral bone. This marked reduction in the outer diameter of the graft had more influence on torsional resistance than did the intracortical porosity of the graft. Demineralized allografts were osteoinductive in only 28% of the cases and appeared to respond in an all-or-nothing pattern. Frozen and thimerosal preserved allografts were the most acceptable substitutes to autografts. PMID- 1516322 TI - Calvarial regeneration in primates with autolyzed antigen-extracted allogeneic bone. AB - The limited regenerative capacity of calvarial membranous bone provides an ideal system for investigation in the comparative physiology of bone regeneration. Cranial defects, 25 mm in diameter, were created in 24 adult male baboons (Papio ursinus). In each animal, defects were implanted with chemosterilized antigen extracted, autolyzed allogeneic (AAA) bone, grafted with iliac corticocancellous grafts, or left ungrafted to monitor the spontaneous regeneration potential of the adult baboon calvaria. Antigen-extracted, autolyzed allogeneic bone implants were prepared from donor sub-adult baboon calvariae and processed so as to retain bone morphogenetic protein (BMP) in the bone matrix. Histomorphometric analysis of undecalcified sections (7-microns thick) prepared from specimens harvested at three, six, and nine months after surgery showed superior osteogenesis in AAA bone matrix implants, compared with autografts and untreated defects. The morphogenetic response was characterized by vascular invasion and mesenchymal cell aggregation after partial resorption and dissolution of the implanted matrix, followed by bone deposition at the calvarial interfaces, the pericranial and endocranial surfaces of the implants, and within the open diploic spaces of the implanted original AAA bone matrix. The superior osteogenesis in AAA bone implants appeared consistent with extensive osteoconductive invasion from the open diploic and endosteal spaces of the recipient calvariae. In addition, the finding of a delicate, trabecularlike bone, appositional to the central areas of the implanted matrix, suggests that AAA bone implants might also have acted as inductive substratum for bone differentiation. PMID- 1516323 TI - The effects of fat interposition for central-physeal defects. A histologic study in rabbits. AB - The effects of autogeneic fat interposition in a central cylindrical physeal defect were observed in rabbits. A 3.6-mm longitudinal drill hole was made across the physis of the distal femur, bilaterally, in four- to six-week-old New Zealand rabbits. One side was filled with an autogeneic fat graft and the contralateral defect was left as a control. The rabbits were killed at intervals during the remaining growth period, and the defects were examined histologically. Although fat grafts reduced the rate of osseous bridging across the physis and allowed more longitudinal growth than controls, transverse regeneration of the physis did not occur in the eight-week period preceding closure. The lack of physeal regeneration across the gap may reflect an important difference between central and peripheral defects. PMID- 1516324 TI - On the material and the tribology of alumina-alumina couplings for hip joint prostheses. AB - The yearly sphericity deviation ranged from 0.03 mu to 3.7 mm in 48 retrieved implants with alumina--alumina bearing balls and cups. Excessive amounts of wear are predominantly design dependent or caused by malalignment. But the abrasion phenomena occurring in the cup centers and in the corresponding ball areas are related to unfavorable function zones. The influence of the lubricating gap geometry as studied in laboratory tests shows the form of sphericity deviations to be of decisive importance for wear and friction, if extended over small angles. Then, the contact stresses attributable to the actual effective curvatures of the bearing exceed the resistance to abrasion of the material under boundary lubrication conditions. There are remarkable differences between the early and actual material quality. Based on the state of knowledge of material aspects of wear criteria for the optimization of material and design, promising tolerable wear rates may be achieved. PMID- 1516325 TI - Cartilage healing after laser surgery. PMID- 1516326 TI - Hip fusion. PMID- 1516327 TI - Ceramic-plastic material as a bone substitute. 1963. PMID- 1516328 TI - Long-term effects of alumina components in total hip prostheses. AB - Six pairs of alumina components of Ceraver-Osteal total hip prostheses, which were implanted from nine to 12 years, were studied. In the load-bearing areas, the wear takes the form of relief polishing. The depth of wear, after a running in period, is less than 0.3 microns and then reaches an equilibrium. In four cases, there was no displacement of the sockets and wear tracks were formed on the femoral heads, the sockets being worn on their periphery, never on the apex. In the case of two persons weighing more than 90 kg, two wear tracks were observed on the heads, corresponding to walking and raising from a seated position. In the worst case, the depth of the wear track was 44 microns and the weight of alumina debris was estimated to be 18 mg. PMID- 1516329 TI - Ten-year survivorship of cemented ceramic-ceramic total hip prosthesis. AB - In the first 187 consecutive alumina-alumina combination hip arthroplasties performed from 1977 to 1979, both components were cemented with conventional techniques. At ten-year follow-up evaluation, 87 patients were reviewed or interviewed by telephone, 37 were dead, 39 were lost to follow-up evaluation, and 24 failures were reoperated on before the end of ten years. The major cause of failure was aseptic loosening of the acetabular component (15 failures). Fracture of the socket and of the femoral head occurred in five patients in this series. However, these complications were not seen with components manufactured after 1979. At the end of ten years, survivorship analysis depicted a 82.59% survival rate when reoperation was considered as failure and a 88.57% rate when reoperation for aseptic loosening was considered as failure. The femoral component had a 99.16% survival rate and the acetabular component had an 88.57% survival rate when reoperation for aseptic loosening was considered as failure. Age, appearance of a two- or three-zone demarcation at the intermediate follow-up evaluation, and outer diameter of the acetabular component were the major parameters influencing the results. Better results observed in the population younger than 50 years of age may be related to the small amount of wear debris produced by the alumina-alumina combination. This combination in hip prosthesis is secure, but should be implanted in young and active patients; the outer diameter of the acetabular component must be at least 50 mm. The major problem that remains is the socket's fixation. It could be improved by a design modification, by choosing another mode of fixation, or both. PMID- 1516330 TI - Sixteen-years' experience with ceramic hip prostheses. AB - The introduction of alumina ceramic combined with the self-locking principle by surface increase has many followers. There is no manufacturing company in the world that does not produce self-locking hip prostheses with ceramic components. Despite increased interim results with conventional prostheses by improved cement technique, the self-locking principle with wear resistant ceramic components is better, at least in young, active patients. PMID- 1516331 TI - Ten- to 14-year results of a ceramic hip prosthesis. AB - One hundred total hip arthroplasties with a cementless aluminum oxide socket and ball with different types of cemented metal femoral stems were performed from 1974 to 1979. All were primary implantations. These cases were recently reviewed in a ten- to 14-year follow-up evaluation. Despite extensive laboratory testing of the ceramic material, a significant number of cases resulted in a very unfavorable result such as extensive wear, ball fracture, or migration of the socket. Whereas the patients had died or could no longer be traced in the case of 23 prostheses, there were 25 prostheses that had already been exchanged at the time of review for mechanical reasons (two stem fractures, eight ceramic ball fractures) and for component loosening attributable to wear of the alumina components. The remaining 52 prostheses still in place had good clinical results in 80%. However, roentgenographic evaluation of these prostheses revealed signs of loosening in six femoral components and in three sockets. Migration of more than 5 mm was evident in 24 sockets (46% of surviving prostheses). Although this had caused loosening in only three sockets at the time of review, further migration up to the limits of the acetabular region would be a major reason for future failures. PMID- 1516332 TI - Comparison of cemented ceramic and metal-polyethylene coupling hip prostheses in ankylosing spondylitis. AB - Two groups of patients suffering from ankylosing spondylitis were treated by total hip arthroplasty. Twenty-one patients (37 hips) were treated with cemented metal-polyethylene prosthesis, whereas 18 patients (36 hips) had cemented ceramic coupling implants. The two groups had similar preoperative clinical data. The average follow-up period was seven to eight years for both. Each patient was graded clinically (pain, function, range of motion, deformities) and roentgenographically (radiolucent lines, etc.). Patients with metal-polyethylene implants showed important modifications of the bone around the implant. Clinical and roentgenographic results were relatively good in patients with ceramic implants. The results underline the importance of the friction coupling of the implant. PMID- 1516333 TI - Comparison of alumina-polyethylene and metal-polyethylene in clinical trials. AB - The dimensional changes of hip sockets of Muller-type total endoprostheses is the subject of this article. Regular anteroposterior roentgenographs of the pelvis were taken to determine the orientation of the center of the prosthetic head in relation to the wire marker of the polyethylene cup. Three different materials used for the femoral balls and matched with polyethylene as socket material were investigated, and the results of the displacement of the ball into the socket were compared. Both creep and wear contribute to the dimensional changes of the hip sockets; the proportional amount of each mechanism is not known. Data from laboratory examinations suggest a relatively high rate of creep in the first six months after implantation. With longer periods, the dimensional changes are predominately caused by wear. In the beginning of joint function, measurements show a high rate of the yearly dimensional changes. The head shifts up to 0.5 mm per year and diminishes after five years to rates of 0.1-0.2 mm, respectively. All dimensional changes that exceed a shift of the head of 0.2 mm per year are considered to be unfavorable and to contribute to loosening of the implants. Using metallic balls (Protasul-2), 64% had a wear rate of less than 0.2 mm; of those using Prostasul-10, 77% had lower rates than 0.2 mm. In patients where ceramic balls were implanted, the displacement rate was below 0.2 mm per year in 95%. Therefore, ceramic seems to be the most favorable material. PMID- 1516334 TI - Alumina versus polyethylene in total knee arthroplasty. AB - The cementless alumina total knee prosthesis, which uses alumina in the portions coming in contact with the bone and a combination of alumina and ultra-high molecular-weight polyethylene (UHMWPE) in the sliding portions, is referred to as a total condylar. Alumina total knee arthroplasty was performed on 137 patients, including 103 rheumatoid arthritis (RA) and 34 osteoarthrosis (OA) patients, from January 1982 to February 1985. The follow-up period was seven years 11 months and four years ten months, respectively. At follow-up evaluation, 108 patients were available for clinical and roentgenographic examinations, amounting to a 79% follow-up rate. At follow-up examination, 67 joints (62%) were completely pain free and 28 joints (26%) caused slight pain on bearing weight. Walking ability was recovered moderately in RA and markedly in OA. In RA, 14 of 84 knees were cemented and one knee was treated with loosening. Of 72 cementless implantations, 55 sustained displacing distally and one sustained loosening in the tibia, whereas 31 sustained displacing proximally and six sustained loosening in the femur. In OA, 21 cementless knees had 17 displacings in the tibia, and ten displacings and two loosenings in the femur. Scanning electron microscopy (SEM) observation of the UHMWPE surface in tibial plates revealed smoothing and burnishing. Alumina is far superior to metal for the sliding part, although it is not always best for the portion in contact with the bone. To resolve these problems, for cementless fixation, anchoring portions of Ti alloy and alumina implants were covered with beads and coated with hydroxyapatite. For cement fixation, "the interface bioactive bone cement technique" interposing hydroxyapatite granules between bone and cement was performed. PMID- 1516335 TI - The radiological investigation of oropharyngeal dysphagia. PMID- 1516336 TI - Thrombolysis in high risk patients. AB - The advent of intra-arterially administered thrombolytic agents of minimal antigenicity, together with small gauge good torque control catheters, enables thrombolysis to be used in patients that may previously have been deemed unsuitable for thrombolytic therapy. Thrombolysis may be used even in the presence of factors formerly and empirically considered to be contra-indications. The continued use of thrombolytic agent may also be warranted despite iatrogenic complications such as vessel wall perforation, particularly if the alternative is major amputation. We report on a series of eight patients in whom intra-arterial tissue plasminogen activator was used despite either recent vascular surgery, or iatrogenic vessel perforation. Suggestions for the use of thrombolysis in high risk patients and following iatrogenic complications are discussed. PMID- 1516337 TI - Proton NMR relaxation times in the normal human liver at 0.08 T. AB - The spin-lattice (T1) and spin-spin (T2) relaxation times of liver in 42 normal volunteers (21 male and 21 female) were measured using a calibrated 0.08 T resistive imager capable of accurate and reproducible relaxometry. T1 was determined using an interleaved gradient echo saturation recovery and inversion recovery technique and T2 using a four-echo Carr-Purcell-Meiboom-Gill sequence. The ranges obtained were T1 = 213 +/- 14 ms and T2 = 66 +/- 5 ms. More specific ranges were obtained for each sex and for younger and older subjects. A small variation in T1 was found between older (greater than 40 years) and younger (less than 40 years) subjects, but no such effect was observed in the case of T2. No significant variations were found when female volunteers were imaged at weekly intervals through the menstrual cycle, when a male volunteer was imaged repeatedly over the course of several months or when male volunteers consumed small quantities of alcohol. PMID- 1516338 TI - Undifferentiated carcinoma of the thyroid gland: sonographic findings. AB - We report high resolution sonographic (7.5 MHz) findings in four cases of undifferentiated carcinoma of the thyroid gland. Sonographic findings in these four cases included poorly marginated, hypoechoic masses associated with calcifications, and invasion of adjacent cervical structures. A knowledge of the sonographic features of undifferentiated carcinoma of the thyroid gland is of clinical importance, since the tumour has a grave prognosis, quite different from the relatively favourable prognosis of well differentiated thyroid carcinoma. PMID- 1516339 TI - The sonographic appearances in postpartum thyroiditis. AB - During the postpartum period about 50% of women with circulating thyroid autoantibodies develop a transient autoimmune thyroiditis. To determine the sonographic appearances in postpartum thyroiditis (PPT), serial ultrasound (US) scans of the thyroid were performed in 135 postpartum women who were divided into three clinical groups: Group 1, 37 antibody positive subjects who developed PPT; Group 2, 28 antibody positive subjects in whom thyroid function remained normal; Group 3, 70 antibody negative controls. Thyroid hypoechogenicity was observed in 14/31 patients (45%) who were scanned between 4 and 8 weeks postpartum and who subsequently developed PPT (Group 1) compared with 4/24 patients (17%) in Group 2 (P less than 0.05) and 1/65 patients (1.5%) in Group 3 (P less than 0.001). In antibody positive patients, the positive predictive value of an abnormal scan during this period was 78%. Between 15 and 25 weeks postpartum thyroid hypoechogenicity was present in 32/37 patients (86%) in Group 1 compared with 11/28 patients (39%) in Group 2 (P less than 0.001) and 2/70 patients (3%) in Group 3 (P less than 0.001). Sonographic abnormality persisted beyond 32 weeks postpartum in 36/41 antibody positive patients (87%) who had exhibited thyroid hypoechogenicity earlier during the study and who had late scans. The characteristic US appearance in PPT is thyroid hypoechogenicity. The role of sonography in the prediction, diagnosis and follow up of patients with PPT is discussed. PMID- 1516340 TI - Gigantiform cementoma occurring in two populations, London and Hong Kong. AB - The gigantiform cementoma presents as multiple opacities in the tooth-bearing areas of the jaws. Sixteen cases are presented, six of British Negresses and 10 of Hong Kong Chinese females. The differential diagnosis and management are briefly reviewed. PMID- 1516341 TI - CT findings in paranasal aspergillosis. AB - Computed tomographic (CT) scan of eight cases of paranasal sinus aspergillosis were reviewed. Different CT patterns were observed such as areas of high densities, linear interlacing network of high density, radiolucent thin rim periphery to the masses, calcification, expansion of involved sinuses and bone erosion. Two cases of invasive type showed extension beyond the sinuses into the orbit and intracranially simulating a malignant tumour. The findings are similar to those described by previous authors. The differential diagnosis is also discussed. PMID- 1516342 TI - Abdominal radiography in suspected 'body packers'. AB - Drug smuggling by intra-abdominal concealment is now a world-wide problem. This paper describes the establishment of a plain radiography service to assist customs officers of Manchester International Airport (MIA) in their work. Over a 2 1/2 year period, 158 suspected 'body packers' were radiographed, resulting in nine positive detections. The existence of the service has resulted in the apparent abandonment of MIA as a port of entry by an organized group of cocaine smugglers. Practical and ethical problems are described. This service is felt to be essential by the customs officers and a valuable service to society by the radiologists and hospital authorities concerned. PMID- 1516343 TI - Soft-tissue localization of 99mTc-hydroxymethylene diphosphonate due to interaction with calcium. AB - Soft tissue localization of 99mTc-labelled bone imaging agents is often associated with high calcium levels either locally or systemically. This could be due to the formation of a large molecular complex after administration of the radiopharmaceutical. We have investigated the formation of such a complex between 99mTc-hydroxymethylene diphosphonate (HMDP) and calcium by a number of techniques. The results indicate that 99mTc-HMDP is a colloidal preparation which may contain particles up to 280 nm in size, and that the labelled colloid may aggregate in the presence of calcium salts forming particles up to 3 microns. Such particles are too large to permit free diffusion across vascular epithelium but large enough to localize in the liver or lungs. It is suggested that this interaction may be responsible for soft tissue localization of the technetium labelled bone imaging agents. In vivo the radiolabelled complex in a mixture of 99mTc-HMDP and calcium chloride localizes to a significantly larger extent in liver, spleen and muscle and less in bone compared with 99mTc-HMDP diluted with saline. The increased liver and spleen uptake can be prevented by prior administration of non-radioactive colloid but this does not significantly improve the bone uptake of the 99mTc-HMDP/calcium chloride mixture. The clinical relevance of these findings lies in their possible explanation for soft-tissue uptake and poor bone accumulation of the technetium-labelled diphosphonates in some patients. This may be particularly important in evaluating quantitative bone scans, especially if serial scanning is done to monitor disease progress or therapy since local or systemic calcium levels may change between scans. PMID- 1516344 TI - Tc HMPAO-labelled white cell scintigraphy in Crohn's disease of the small bowel. AB - 99mTechnetium-hexamethyl propylene amine oxime (99mTc HMPAO) white cell scintigraphy is increasingly used in the investigation of inflammatory bowel disease. It is now an accepted technique in the assessment of patients with colitis, although its role in small bowel is less clear. A retrospective study was performed on patients with jejunal and ileal Crohn's disease to assess the sensitivity, reliability and usefulness of this technique in small bowel disease. Tc HMPAO scintigraphy was compared with barium studies, clinical outcome and, where available, subsequent histology. Good correlation between this technique and barium studies was found in 14 out of 18 patients and additional information was provided in two patients. A single false positive scan highlights the importance of early scanning in avoiding errors of interpretation due to the normal hepatobiliary excretion of activity that occurs with this pharmaceutical. PMID- 1516345 TI - Double blind comparison of Iomeprol 350 and Iopamidol 340 in intravenous digital subtraction angiography for peripheral vascular disease. AB - A randomized double blind study was undertaken to compare the diagnostic efficacy and side effects of a new non-ionic contrast medium Iomeprol with a commonly used one--Iopamidol. Visual and densitometric comparison was made of intravenous digital subtraction angiograms performed for peripheral vascular disease. The results show the two media to be similar both in imaging quality and in the incidence of associated side effects. Ninety-eight per cent of the intravenous digital subtraction angiograms were assessed as adequate for clinical management by the vascular surgeon. PMID- 1516346 TI - The prevalence of enlarged mediastinal lymph nodes in asbestos-exposed individuals: a CT study. AB - Patients with cryptogenic fibrosing alveolitis have a higher prevalence of enlarged mediastinal lymph nodes compared with the normal population. To determine whether or not this observation applies to individuals with asbestos induced pulmonary fibrosis the high resolution computed tomography (CT) scans of 14 patients with definite asbestosis and 11 age-matched cases with benign asbestos-induced pleural disease, but no lung disease, were re-imaged on soft tissue settings. The site, size and number of mediastinal lymph nodes equal to, or greater than, 1.2 cm were recorded. In the asbestosis group 14 out of 14 patients had at least one enlarged lymph node with an average number per individual of four (range 1-10). In the control group two out of 11 patients each had one minimally enlarged lymph node. We conclude that mediastinal lymph node enlargement occurs frequently in asbestosis: awareness of this is important in the investigation of malignant disease in patients with asbestosis. PMID- 1516347 TI - Patterns of breast calcification in patients on renal dialysis. AB - Patients on renal dialysis are prone to form areas of metastatic calcification in soft tissues. In this study we have analysed the mammograms of 16 women on renal dialysis and compared them with a control group of 32 women attending for routine mammographic screening. We found a significant increase in vascular and parenchymal calcifications in the women on renal dialysis. Ductal calcifications were no more prevalent in the patients on dialysis, and in no case did the calcification simulate malignancy. PMID- 1516348 TI - Case report: limey urine. AB - A case is described of multiple tiny bladder stones giving rise to unusual ultrasound and plain radiograph appearances of a calcified sediment within the bladder. PMID- 1516349 TI - Case report: granular cell tumour of the breast. AB - We describe a granular cell tumour in the breast of a 62-year-old woman. This tumour is unusual in the breast, and though usually benign, may be misinterpreted as cancer. PMID- 1516350 TI - Case report: the ultrasound diagnosis of enterocutaneous fistula. AB - The sonographic diagnosis of post-operative enterocutaneous fistula is presented. This has not previously been reported in the English literature. PMID- 1516351 TI - Case report: acute subdural haematoma--an unusual presentation of a meningioma. AB - Acute subdural haemorrhage is usually the result of a head injury, but when it occurs without a history of trauma, an underlying cause must be suspected. An unusual case is described of an acute subdural haematoma in association with a parasagittal meningioma. This is a rare but serious complication of a meningioma and outcome depends upon prompt removal of the tumour. PMID- 1516352 TI - Case report: lipoma of the liver--ultrasound, CT and MR imaging. AB - A case of lipoma of the liver is presented; ultrasound, computed tomography (CT) and magnetic resonance imaging (MRI) findings are reviewed and compared with previous reports. The ultrasound pattern and appearance of the tumour in CT as well as MRI are discussed. PMID- 1516353 TI - Case report: fatal non-menstrual toxic shock in a Chinese woman. AB - A fatal case of non-menstrual toxic shock syndrome (TSS) is reported in a Chinese woman, which was associated with a vaginal Staphylococcus aureus infection. Cerebral haemorrhage and vasogenic white matter oedema was shown in cranial computed tomography (CT) before the terminal event. PMID- 1516355 TI - Brachial arteriography--which technique is best? PMID- 1516354 TI - Brachial arteriography--which technique is best? PMID- 1516356 TI - Bile duct wall thickening. PMID- 1516357 TI - Bile duct wall thickening. PMID- 1516358 TI - Patient monitoring in radiology. PMID- 1516359 TI - Multielement visual tracking: attention and perceptual organization. AB - Two types of theories have been advanced to account for how attention is allocated in performing goal-directed visual tasks. According to location-based theories, visual attention is allocated to spatial locations in the image; according to object-based theories, attention is allocated to perceptual objects. Evidence for the latter view comes from experiments demonstrating the importance of perceptual grouping in selective-attention tasks. This article provides further evidence concerning the importance of perceptual organization in attending to objects. In seven experiments, observers tracked multiple randomly moving visual elements under a variety of conditions. Ten elements moved continuously about the display for several seconds; one to five of them were designated as targets before movement initiation. At the end of movement, one element was highlighted, and subjects indicated whether or not it was a target. The ease with which the elements in the target set could be perceptually grouped was systematically manipulated. In Experiments 1-3, factors that influenced the initial formation of a perceptual group were manipulated; this affected performance, but only early in practice. In Experiments 4-7, factors that influenced the maintenance of a perceptual group during motion were manipulated; this affected performance throughout practice. The results suggest that observers spontaneously grouped the target elements and directed attention toward this coherent but nonrigid virtual object. This supports object-based theories of attention and demonstrates that perceptual grouping, which is usually conceived of as a purely stimulus-driven process, can also be governed by goal-directed mechanisms. PMID- 1516360 TI - The monolingual nature of speech segmentation by bilinguals. AB - Monolingual French speakers employ a syllable-based procedure in speech segmentation; monolingual English speakers use a stress-based segmentation procedure and do not use the syllable-based procedure. In the present study French-English bilinguals participated in segmentation experiments with English and French materials. Their results as a group did not simply mimic the performance of English monolinguals with English language materials and of French monolinguals with French language materials. Instead, the bilinguals formed two groups, defined by forced choice of a dominant language. Only the French-dominant groups showed syllabic segmentation and only with French language materials. The English-dominant group showed no syllabic segmentation in either language. However, the English-dominant group showed stress-based segmentation with English language materials; the French-dominant group did not. We argue that rhythmically based segmentation procedures are mutually exclusive, as a consequence of which speech segmentation by bilinguals is, in one respect at least, functionally monolingual. PMID- 1516361 TI - Common region: a new principle of perceptual grouping. AB - A new principle of grouping is proposed that is based on elements being located within a common region of space. Demonstrations analogous to Wertheimer's original displays show that this factor strongly influences perceived grouping and is capable of overcoming the effects of other powerful grouping factors such as proximity and similarity. Grouping by common region is further shown to depend on perceived depth relations, indicating that it is influenced by processes that occur after at least some depth perception has been achieved. Further demonstrations suggest that it is dominated by the smallest background area and that it can follow a hierarchical embedding scheme. It is argued that common region cannot be reduced to the effects of proximity, closure, or any other previously known factor and therefore constitutes a genuinely new principle of grouping. PMID- 1516362 TI - A review on classical swine fever infections in pigs: epizootiology, clinical disease and pathology. AB - A review is given on classical swine fever (CSF) including epizootiology, clinical disease and pathology. Under the item of epizootiology the history of CSF is briefly summarized. Ways of transmission are described with special reference to CSF in wild boars. The chapter about clinical disease includes the description of different courses of CSF such as peracute, acute, subacute form and chronic disease with reference to the course of transplacental infection and fate of the progeny associated with the "carrier sow syndrome". The most typical lesions in CSF are summarized in the chapter of pathology. PMID- 1516363 TI - A tissue culture vaccine with lapinized chinese (LC) strain of hog cholera virus (HCV). AB - The lapinized chinese (LC) strain of hog cholera virus (HCV), was adapted to grow in a cell line from minipig kidney (MPK) where it reached a titer, as determined by immunofluorescence, significantly higher than in rabbits. Inasmuch as the immune serum to HCV neutralized the culture-adapted virus, it was concluded that its antigenicity did not undergo any change after adaptation to MPK cells. The MPK-LC adapted virus (MPK-LC-HCV) showed also a higher immunogenic activity in rabbits, in comparison with the original LC virus. The MPK-LC-HCV protected pigs against challenge infection with virulent HCV. Thus, the vaccinated pigs did not show any clinical signs of disease, nor have they been responsible of virus shedding after they were exposed to the challenge infection 1 month or 6 and 11 months later. All vaccinated pigs seroconverted after vaccination and the antibody titers were on the same range of those reported in pigs vaccinated with the traditional vaccine prepared in rabbits. In the same pigs the antibody concentration underwent a booster effect following challenge infection. It was suggested the MPK-LC-HCV vaccine as an alternative product that might be used to prevent HCV infection. prevent HCV infection. PMID- 1516364 TI - Hulka Clip application as a potential cause of chronic pelvic pain. AB - A case report of an isolated hydrosalpinx resulting from the placement of two Hulka Clips on the same fallopian tube is presented. This is a previously unreported complication of mechanical sterilization and is suggested as a possible cause of chronic pelvic pain. PMID- 1516365 TI - Progesterone-releasing vaginal rings for use in postpartum contraception. I. In vitro release rates of progesterone from core-loaded rings. AB - Vaginal rings of Dow Corning 382 Silastic polymer, having identical outside dimensions, were fabricated to contain cores of different diameters loaded with 25% w/w progesterone. Elution of rings was carried out in continuously flowing baths of isotonic saline at 37 degrees C and quantities of progesterone released in 24 h periods measured for up to 128 days. Release of the steroid was shown to be a membrane diffusion-controlled process, modified by the development of a gradually increasing zone of depletion at the core surface. Rings of a suitable core diameter were selected to give initial release of 5 mg/24 h progesterone and sterile batches of these rings, prepared for WHO-sponsored clinical studies in post-partum, lactating women, were shown to give highly consistent and reproducible rates of in vitro drug delivery. A comparison was made with the in vitro release rates of rings containing a homogeneous dispersion of progesterone. PMID- 1516366 TI - Progesterone-releasing vaginal rings for use in postpartum contraception. II. Pharmacokinetic profiles in women. AB - Vaginal rings releasing progesterone with 3 different initial release rates (5, 8 and 20 mg/day) were used by 11, 10 and 10 women, respectively. The period of insertion was 90 days. The 5 and 8 mg/day rings consisted of a core loaded with progesterone, the 20 mg/day ring contained progesterone homogeneously distributed throughout the mass of the ring. Notwithstanding these differences, the total progesterone levels (areas under curve) were directly related to the release rates. So were the rates of decrease of progesterone levels during the 90 days of insertion of the ring. They were 25, 31 and 47% for the rings releasing 5, 8 and 20 mg/day, respectively. PMID- 1516367 TI - Postpartum IUDS: keys for success. AB - Intrauterine device (IUD) insertion is convenient and efficient in the postplacental and immediate postpartum periods. Insertion at these times is demonstrably safe, having a low incidence of infection, few bleeding problems, and low perforation rates. IUD expulsion rates can vary widely, and are a function of timing of insertion, type of IUD, and insertion technique. When a copper T device is inserted postplacentally or immediately postpartum by an experienced and trained clinician, expulsion rates of about 7-15 per 100 users at six months can be expected. Women must be told how to detect expulsions and instructed to return for reinsertion or for another method. Most investigators emphasize that high fundal IUD placement will reduce the expulsion rate. Unplanned pregnancy rates for postplacental IUD insertion range from 2.0-2.8 per 100 users at 24 months when using modern copper IUDs, correct insertion technique, careful postinsertion instructions and good follow-up. Postplacental insertions are performed manually or with a ring forceps. Immediate postpartum insertions (10 minutes to 48 hours after delivery) are performed with the ring forceps. PMID- 1516368 TI - Accuracy of recall of use of an intrauterine device. AB - Within a case-control study of the relationship between oral contraceptives and breast cancer, information on other contraceptive practices, including use of an intrauterine device (IUD) was obtained through interviews of study subjects and from the records of gynaecologists. Information from these two sources was compared for 239 women who had ever used an IUD. The results showed that agreement on total duration, number of IUD episodes, and time since first and time since last IUD use was excellent. As approximately 75% of IUDs used were unknown, agreement on brands could not be investigated. Studies investigating the effects of individual types of IUDs should use physician records as an additional source of information. PMID- 1516369 TI - GnRH antagonists suppress prolactin release in non-human primates. AB - GnRH antagonists, such as Antide, are being evaluated for potential contraceptive applications. Although their contraceptive efficacy clearly results from their rapid inhibitory effects on gonadotropin release, there remains the possibility of other incidental effects. Under certain physiological conditions, the release of prolactin (Prl) appears to be temporally related to the secretion of luteinizing hormone (LH) and hence by inference to the secretion of GnRH. Here, we examined the effects of the GnRH antagonist Antide on the release of LH and Prl. Under agonadal conditions, a remarkable concordance was seen between LH and Prl pulses with up to 100% of pulses being coincident. Administration of Antide resulted in a rapid parallel decline in both LH and Prl with LH levels falling by 50% within 2 h and Prl levels falling by 30-40%. At this dose of Antide (1.0 mg/kg, sc), pulsatile release of LH and Prl continued albeit at a much reduced amplitude. The administration of a bolus of exogenous GnRH in the face of GnRHant induced suppression resulted in prompt release of LH and Prl in all 3 monkeys. Since Antide inhibits the release of LH and Prl in a parallel fashion, and GnRH re-stimulates the release of both hormones in a parallel fashion, we conclude that the synchronous pulsatile release of LH and Prl observed in the agonadal monkey is due to a direct action of GnRH. What this action is for Prl release, and how it relates to the control of dopamine or other neuroendocrine mechanisms normally controlling the release of Prl remains unclear. It also remains to be seen whether this GnRH antagonist-induced suppression of Prl will have physiologic significance. PMID- 1516370 TI - Interference with ovulation and luteal function by human ovarian follicular fluid peptide in bonnet monkeys, Macaca radiata. AB - Partially purified human ovarian follicular fluid peptide (hGF2) was administered during follicular phase in 5 bonnet monkeys. In control as well as hGF2-injected animals, ovulation was synchronized by treatment with FSH, Pergonal and hCG. All the 5 control bonnet monkeys showed plasma estradiol peak followed by increased progesterone levels. In 4 out of 5 hGF2-injected animals, plasma progesterone levels were drastically reduced. Plasma estradiol levels were decreased only in 3 animals in which amenorrhea was observed. These data reveal that hGF2 injection disrupted ovarian function in bonnet monkeys. PMID- 1516371 TI - Pediatric dermatology. PMID- 1516372 TI - Suction purpura: Part II. "Car seat" and other mechanical purpuras. PMID- 1516373 TI - Childhood warts. PMID- 1516374 TI - A dermatologic diary. Portrait of a practice. PMID- 1516375 TI - Facial psoriasis. AB - The face has been cited as being the least affected body surface in patients with psoriasis. It also has been reported that psoriasis of the face is more prevalent in children than in adults, and when it does occur, at any age, the face is never the only body part involved. In fact, face involvement may reflect a high degree of severity of psoriasis. PMID- 1516376 TI - Eruptive xanthoma. AB - We recently had occasion to diagnose eruptive xanthoma. The significance of this cutaneous finding is that it is indicative of an underlying hypertriglyceridemic state. Appropriate dietary changes, correction of secondary factors, along with the addition of antihyperlipidemic drugs as required, will lower the plasma triglyceride level and allow the xanthomatous lesions to resolve. PMID- 1516377 TI - Multiple epidermoid cysts in a renal transplant recipient taking cyclosporine A. AB - A forty-two-year-old male recipient of a cadaver renal transplant showed multiple nodulocystic lesions on his back and lateral aspects of his neck four months after beginning immunosuppressive therapy with cyclosporine A and prednisone. Results of histopathologic studies revealed that they were epidermoid infundibular cysts. We note the relationship between this clinical appearance and cyclosporine A, as well as this agent's cutaneous side effects. PMID- 1516378 TI - Folic acid and vitamin B12 in vitiligo: a nutritional approach. AB - When compared with the normal population, patients with vitiligo often showed diminished blood levels of folic acid. In a group of fifteen patients with vitiligo, folic acid levels were below normal in the serum of eleven patients, in the whole blood of five patients, and in the erythrocytes of six patients. Vitamin B12 serum levels were below normal in five of the fifteen patients. Ascorbic acid plasma levels were also lowered in four of the patients. In eight patients prolonged oral administration of folic acid with simultaneous parenteral treatment with vitamin B12 and oral ascorbic acid was followed by definite repigmentation without side effects. PMID- 1516379 TI - Systemic amyloidosis secondary to chronic leg ulcers. AB - Chronic leg ulcers due to any cause are almost invariably associated with an inflammatory process. As with any long-standing inflammation, leg ulcers may be complicated by systemic amyloidosis, which occurs in rheumatoid arthritis, cystic fibrosis, tuberculosis, and other disorders. There are, however, very few reports on the association between these two conditions. We report a patient with severe leg ulcers of twenty years' duration in whom reactive systemic amyloidosis presented as a nephrotic syndrome. PMID- 1516380 TI - Calcification of the auricular cartilage: a case report and literature review. AB - We report a case of auricular calcification in an elderly man with a history of frostbite and normal serum calcium levels. The causes of calcification of the cartilage of the external ear are discussed. PMID- 1516381 TI - Treatment-resistant psoriasis due to a mastectomy sleeve: an extensive Koebner response. AB - The Koebner or isomorphic response refers to the appearance of a dermatosis at sites of trauma. This process was first described by Heinrich Koebner in a man with psoriatic plaques in areas of trauma. Many types of trauma are capable of producing koebnerization. We report a case of extensive koebnerization in response to the wearing of a mastectomy sleeve, worn to reduce lymphedema. Both the chronic pressure produced by the device and the trauma of applying the sleeve produced the necessary dermal and epidermal trauma to elicit the Koebner response. PMID- 1516382 TI - Diffuse necrobiosis lipoidica diabeticorum. PMID- 1516383 TI - The tip of the thromboembolism iceberg. PMID- 1516384 TI - What is the origin of pleural transudates and exudates? PMID- 1516385 TI - Cytokine mRNA profile and cell activation in bronchoalveolar lavage fluid from nonatopic patients with symptomatic asthma. AB - Recent studies have indicated that airway inflammation in atopic asthma is characterized by T-cell activation and local eosinophilia, but it is unknown whether this also applies to nonatopic asthma. In this study, the cytokine mRNA profile and activation status of inflammatory cells in bronchoalveolar lavage fluid (BALF) of eight nonallergic patients with symptomatic asthma and eight nonallergic healthy controls were compared using the message amplification phenotyping (MAPPing) with the polymerase chain reaction (PCR) procedure and immunocytochemical evaluation. Asthmatics had an increasing number of inflammatory cells in BALF, including activated eosinophils (EG2-positive) (p less than 0.001) and activated T cells (CD25-positive) (p less than 0.001). Activated T cells from five of the eight asthmatic patients and from one control subject expressed high levels of interleukin 5 (IL-5) and granulocyte-macrophage colony-stimulating factor (GM-CSF). All the asthmatic patients had increased numbers of monocytes in their BALF (p less than 0.002) and those cells invariably showed increased expression of interleukin 1 beta (IL1 beta) transcripts. In five patients they also expressed appreciable levels of IL-6 and GM-CSF mRNA. IL-5 and GM-CSF can induce local activation of eosinophils, and IL-1 beta and IL-6 are known to promote T-cell activation and proliferation. Thus, there is an increased production of cytokines with inflammatory properties in the airways of patients with nonatopic symptomatic asthma, which may contribute to the persistence of inflammation, and monocytes and activated T cells are important sources of these cytokines. PMID- 1516386 TI - Deep venous thrombosis and the risk of pulmonary embolism. A systematic study. AB - The influence of several diseases and clinical conditions on the presence of pulmonary embolism (PE) in a large series of patients with deep venous thrombosis (DVT) in the lower extremities was analyzed prospectively. Lung scan findings from a series of 434 consecutive patients with DVT (with and without symptoms of PE) were studied and then correlated to five clinical variables: age, sex, elapsed time since clinical symptoms had appeared in the leg to diagnosis, degree of proximity of venous thrombus, and the presence or not of several risk factors that could have predisposed to thrombus development. According to scintigraphic findings, 164 patients were considered to have PE (asymptomatic in 76 of them), while 200 patients were classified as having only DVT. Lung scan was considered to be indeterminate for PE in 70 patients, and they were not included in the study. No differences were found in terms of age, sex, interval of time elapsed since onset of symptoms to diagnosis, or in the degree of proximity of the thrombus. However, several differences between groups were found when comparing the presence or absence of several predisposing factors for thrombosis: DVT developing in immobilized patients was associated with a significantly lower incidence of PE as compared with nonimmobilized patients (p = 0.005). Conversely, patients with a history of venous thromboembolism (VTE) had a significantly higher rate of embolism (31/51 vs 133/313; p = 0.01). On logistic regression analysis, a history of VTE showed a statistically significant association with more than a twofold higher risk of having PE for patients with such an antecedent. Our findings suggest that different pathophysiologic pathways could perhaps explain differences in embolic potential. PMID- 1516387 TI - Association between neutrophil concentration in bronchoalveolar lavage fluid and recent losses in diffusing capacity in men formerly exposed to asbestos. AB - It has been observed widely that some individuals exposed to asbestos will experience continued losses of lung function after asbestos exposure ceases. Unfortunately, there are few data on factors that determine clinical course, limiting the clinician's ability to determine prognosis in an individual case and restricting the possibility for testing or targeting any potential intervention to alter the course among the millions at risk. In an attempt to address this question, we studied a volunteer population of 50 such men from among a stable, heterogeneous population of asbestos-exposed workers who had been continuously followed in our occupational medicine clinics for up to 12 years (mean, 6.3 years); most had some clinical or roentgenographic sign of asbestos effect, pleural or parenchymal. Each subject was reexamined clinically, functionally, and roentgenographically. Asbestos and tobacco exposure histories were carefully reviewed with the subjects and quantified based on these reports and available data regarding the various work environments from which they came. Subsequently, each underwent a bronchoalveolar lavage to assess cellularity and levels of various proteins. The levels of risk factors, clinical findings, and biologic parameters from lavage were examined for their relationship to serial changes in lung function during the period over which they had been previously followed. Results of the study demonstrate that serial changes in lung function were not closely related to level or length of prior exposure, smoking behavior, chest roentgenographic findings, or lung volumes. Progressive loss of diffusing capacity for carbon monoxide (Dco) was significantly associated with two factors: level of neutrophil concentration in lavage fluid (0.043 +/- 0.016 ml/min/mm Hg/yr drop for each 0.1 x 10(4) neutrophils per milliliter, p = 0.02) and the level of Dco itself (0.17 +/- 0.07 ml/min/mm Hg/yr drop for each 10 percent decrease in percent Dco predicted, p = 0.01). The relationship with neutrophil concentration was statistically independent of the association with Dco itself and stronger; it persisted when loss of Dco was adjusted for baseline value. Lung volume changes were not associated with any predictor variables, alone or in combination. We conclude that the presence of neutrophils in bronchoalveolar lavage fluid is associated with recent disease progression that may have implications in studies of the mechanisms of asbestos-associated disease and in clinical treatment of patients at risk. PMID- 1516388 TI - Association between acute inflammatory cells in lavage fluid and bronchial metaplasia. AB - In epidemiologic studies, airway disease and parenchymal injury are known morbid outcomes of occupational exposure to asbestos. However, the relationship of inflammatory events considered to be responsible for parenchymal injury to the subsequent development of airway injury is unknown. To assess this we performed bronchoalveolar lavage (BAL) and airway biopsies on a population of subjects with exposure to asbestos in the workplace. As an index of airway injury, we employed histologic metaplasia seen in mucosal biopsy specimens. Lung BAL fluid was analyzed for two potentially relevant protein markers and for inflammatory cells recovered from the lower respiratory tract. We related metaplasia to demographic features of this study population (eg, smoking history and asbestos exposure data) and also to the protein and cellular markers recovered by BAL. We studied 50 workers and detected keratinizing metaplasia in 15 and varying lesser abnormalities in the other 28. Cigarette smoking was not associated with the presence of metaplasia (p less than 0.2). Smoking status was associated with an increase in BAL cells (p less than 0.02); however, neither the percent nor concentration of acute inflammatory cells was significantly increased. Acute inflammatory cells (percent and cells per milliliter of BAL fluid) were significantly increased among the subjects with severe metaplasia compared with other study subjects. This increase was true of both neutrophils and eosinophils and the sum of these two (p less than 0.02). Stratification of subjects by smoking status demonstrated a persistent association of inflammatory cells with metaplasia. By logistic regression analysis, polymorphonuclear leukocytes per milliliter and eosinophils per milliliter were significantly related to the presence of metaplasia in two independent models (odds ratios, 9.9 and 7.6, respectively). Cigarette smoking and other demographic or BAL variables were not significantly associated with metaplasia in these models. PMID- 1516389 TI - Comparison of six oxygen delivery systems for COPD patients at rest and during exercise. AB - Five different oxygen-conserving devices were tested in each of ten oxygen dependent patients with COPD who had met the NOTT criteria for continuous oxygen use. They were tested on room air, their prescribed continuous oxygen flow and then on each of the five devices. The devices which delivered a bolus of oxygen during early inspiration or increased oxygen delivery as the respiratory rate increased did better than those devices which delivered oxygen at a normal flow rate during inspiration or a fixed portion of inspiration. In at least one of the subjects each device was associated with desaturation to less than 80 percent during a 12-min walk. It is concluded that oxygen-conserving devices vary in their ability to maintain SaO2 levels during exercise. It is recommended that a home oxygen evaluation include measurement of an exercise SaO2 utilizing the prescribed oxygen delivery system. PMID- 1516390 TI - Comparison of three different methods used to achieve local anesthesia for fiberoptic bronchoscopy. AB - A patient's tolerance of fiberoptic bronchoscopy depends on the effectiveness of local anesthesia. This study compares the three different methods of local anesthesia in common use After sedation, patients (n = 53) received either 4 ml of 2.5 percent cocaine by intratracheal injection (TI) (n = 18), by bronchoscopic injection (BI) (n = 19), or had 4 ml of 4 percent lidocaine delivered by nebulizer 20 min before the procedure (NEB) (n = 16). Patients and bronchoscopists scored the procedure using visual analog (VAS) and severity scales. Objective measurements of cough counts and episodes of stridor were recorded by phonopneumography. Patients' VAS scores showed a clear preference for the transtracheal method compared with either bronchoscopically injected cocaine (p less than 0.001) or nebulized lidocaine (p less than 0.001). Patients also reported that the TI method produced less cough during intubation of the larynx and inspection of the airways (BI and NEB, p less than 0.01). The TI method was also preferred by the bronchoscopists (BI and NEB, p less than 0.001); they reported less cough and easier tracheal intubation. The mean cough count was significantly lower for the TI group, 49 (43) compared with 95 (52) for BI (p less than 0.01), and 81 (43) for the NEB group (p less than 0.05). Patients' and bronchoscopists' VAS showed significant correlation with cough (r = 0.63-69, p less than 0.01). Stridor occurred in only two patients after TI, compared with 15 in the other two groups. Extra local anesthesia was required by 16 patients after BI, by all the NEB group, but by only one patient after TI. Subjective and objective measurement shows that 4 ml of 2.5 percent cocaine injected into the trachea produced excellent local anesthesia for fiberoptic bronchoscopy, there were no extra complications, and it was the method preferred by both patients and bronchoscopists. PMID- 1516391 TI - Short- and long-term hemodynamic effects of oral nifedipine in patients with pulmonary hypertension secondary to COPD and lung fibrosis. Deleterious effects in patients with restrictive disease. AB - STUDY OBJECTIVE: The present study was undertaken to evaluate at rest the short- and long-term effects of oral nifedipine (N) in patients with pulmonary hypertension (PH). DESIGN AND SETTING: A prospective study with ten consecutive cases during two years in a setting of a district acute hospital. PATIENTS OR PARTICIPANTS: Seven patients with advanced COPD and three with severe lung fibrosis (LF) during a period of stable condition. Three patients with COPD were eligible for the long-term investigation. INTERVENTIONS: Right heart catheterization with a 7F Swan-Ganz triple-lumen thermodilution catheter and radial cannulation with a 3F arterial catheter. MEASUREMENTS AND RESULTS: Measurement of CO, MAP, RAP, PAP, PWP, HR, and ABG and calculation of CI, TSR, PAR, and DO2 before and after 20 mg of N sublingually at rest. For the group as a whole, N induced a reduction in MAP and TSR, with a significant increase in CI and DO2. There were no significant changes in PAP, PAR (magnitude of the reduction: -10 percent), HR, and PaO2. The individual analysis of the driving pressures (PAP-PWP) in function of the cardiac output demonstrated that a real vasodilating effect in the pulmonary circulation occurred in only three COPD patients (magnitude of the PAR reduction: -43 percent), while in the three patients with LF, N induced a deleterious increase in PAP and PAR. After long term treatment (10 mg of N daily every 4 h; average 12 months) in the former, despite a persistent beneficial hemodynamic effect (magnitude of the PAR reduction: -36 percent), there was the usually expected clinical worsening. CONCLUSIONS: N in small doses may be able in some patients with severe COPD to induce a beneficial short- and long-term hemodynamic effect on the pulmonary circulation when PH is present. On the other hand, N should not be used in patients with PH and advanced LF. PMID- 1516392 TI - Bronchiolitis obliterans organizing pneumonia. Clinical features and differential diagnosis. AB - The clinical features of 34 Japanese patients with bronchiolitis obliterans organizing pneumonia (BOOP) are discussed. Thirty-two patients (94 percent) had symptoms of cough, fever, or dyspnea. On chest roentgenograms, bilateral patchy infiltrates were seen most frequently in 23 patients (68 percent), followed by small linear opacities in five (15 percent), both patchy infiltrates and reticulonodular opacities in four (12 percent), and reticulonodular opacities in two (6 percent). The bronchoalveolar lavage fluid (BALF) cell findings obtained from 26 patients revealed an increase in the percentage of lymphocytes in 20 patients (77 percent), neutrophils in 15 (58 percent), and eosinophils in 16 (62 percent), and a decrease in the CD4+/CD8+ ratio in 14 of 23 patients (61 percent). Corticosteroids were administered to 25 patients. Except for one patient who died, the prognosis was good in all patients. Further, in patients without corticosteroid therapy, the prognosis was good. PMID- 1516393 TI - Effects of stopping long-term vasodilator therapy in patients with chronic aortic insufficiency. AB - We studied the effects of stopping long-term vasodilator therapy in 17 patients with chronic stable aortic insufficiency. These patients received hydralazine for 37 +/- 15 months (mean +/- SD) and, as a result, had experienced a significant decrease in left ventricular volumes. All patients were followed clinically and ten of the patients underwent serial radionuclide evaluation at baseline, while receiving drug, and at 20 +/- 7 months after stopping drug therapy. No patient showed evidence of acute clinical deterioration when drug therapy was stopped. The rate of progression to valve replacement due to onset of symptoms or left ventricular dysfunction was not significantly different from that previously reported in a population with similar characteristics. Left ventricular size, however, returned to levels similar to baseline after drug therapy was stopped. We conclude that long-term vasodilator therapy may be discontinued in patients with chronic stable aortic insufficiency without causing clinical deterioration or significant alteration in rate of progression to valve replacement. PMID- 1516394 TI - Intermittent administration of furosemide vs continuous infusion preceded by a loading dose for congestive heart failure. AB - Several reports have suggested that continuous intravenous administration of loop diuretics may be superior to intermittent administration. We performed a prospective randomized crossover study comparing intermittent intravenous administration (IA) of furosemide with continuous infusion following a single loading dose (LDCI) in nine patients with severe congestive heart failure. At the time of hospital admission, patients were randomly assigned to one of two treatment groups. One group (four patients) received an IV bolus injection of furosemide followed immediately by a continuous infusion for 48 h. The second group (five patients) was treated with three IV bolus injections a day for 48 h. Total doses of furosemide were equivalent in the two groups. After 48 h, each patient was crossed over to the other method and treated for an additional 48 h. LDCI produced significantly greater diuresis and natriuresis than IA (total urine output increased by 12 to 26 percent, total sodium excretion increased by 11 to 33 percent) (p less than 0.01). There were no significant differences in side effects between the two methods. These results indicate that LDCI may be a preferred method for administration of furosemide in patients with congestive heart failure. PMID- 1516395 TI - Bronchodilator testing "confidence intervals" based on the level of bronchial responsiveness. AB - "Confidence intervals" based upon inhalation of placebo have been proposed as criteria for defining a significant response to an inhaled bronchodilator. The published intervals were derived from a clinically heterogeneous population. We calculated the difference (delta) between spirometric data before and after placebo in 109 consecutive patients referred for methacholine bronchoprovocation challenge testing. The mean delta, expressed both as a percent change and as actual volume change for both the FVC and FEV1, was not significantly different in patients with bronchial hyperresponsiveness, as compared to subjects with a negative methacholine challenge test; however, the variance of measurements in hyperresponsive subjects was significantly greater than that of the normal population. In addition, as the category of responsiveness increased from mild to moderate to severe hyperresponsiveness, so did the variance within these groups. A negative correlation between the measured PC20FEV1 and the volume and percent change was noted. We conclude that patients with hyperresponsive airways may display increased spirometric variation before and after placebo. This general approach for establishing normal limits for defining a significant response appears to be valid, but the actual values used may vary, depending on the composition of the population tested and the goals of the study. Also, the use of the term, "confidence intervals," in this context is inappropriate; and we propose, instead, the use of percentiles and the simpler terms, upper 90th or 95th percentiles. PMID- 1516396 TI - Transbronchial lung biopsy. Histopathologic and morphometric assessment of diagnostic utility. AB - The diagnostic utility of transbronchial lung biopsy (TBB) is partly a function of its size. However, objective parameters that reflect biopsy specimen size have not yet been well-defined. We studied clinical records and histopathologic lung tissue slides of 116 patients who underwent diagnostic TBB, aiming to define the possible significance of association between seven parameters and three categories of pathologic diagnoses. Three of the seven parameters were clinical: age, sex, and chest roentgenographic infiltrates (localized vs diffuse). The remaining four parameters were histopathologic and morphometric: total number of tissue fragments, total number of alveoli (per biopsy specimen), total tissue area (alveolated plus nonalveolated), and lung total area (alveolated tissue alone). The three categories of pathologic diagnoses were as follows: infection, tumor, and nonspecific diagnoses. The nonspecific diagnoses included diagnoses of fibrosis and/or chronic inflammation. The alveoli were microscopically counted by one of us (S.D.G.). The number of biopsy fragments, the total tissue area, and the total lung area were measured in square millimeters by a computer-assisted digitizing system using specific (Bio-Quant) software (R and M Biometrics Inc). The significance of the associations between the seven parameters and the three diagnostic categories were assessed by the chi2 test for association. Overall, the following four possible associations were found to be statistically significant: (1) age--a lower percentage of patients with infection was found among patients with increasing age (p less than 0.001); (2) roentgenographic findings--a greater percentage of tumor diagnoses were found in patients with localized infiltrates (p = 0.006); (3) number of biopsy fragments--a greater percentage of patients with diagnoses of infection was identified among patients whose biopsy specimens contained the highest number of tissue fragments (p = 0.04); and (4) number of alveoli--a greater percentage of diagnosis of infection was made in patients whose biopsy specimens contained greater than or equal to 20 alveoli (p = 0.01). Our findings support the notion that the diagnostic utility of TBB is related to its size. However, this relationship between TBB size and diagnostic utility was apparent only for diagnoses of infection and not for diagnoses of tumor. We conclude that TBB specimens containing 20 or more alveoli may (1) be declared to be adequate for diagnosis, (2) in the appropriate clinical setting, they will be most likely to yield a diagnosis of infection, and (3) the number of alveoli does not appear to be associated to the diagnosis of tumor. PMID- 1516397 TI - Distilled water challenges in asthmatic children. Comparison of different protocols. AB - Inhalation of ultrasonically nebulized distilled water (UNDW) appears a promising candidate for routine challenge testing in bronchial asthma. We have compared two different methods of application of UNDW in 12 asthmatic children with a positive response to methacholine provocation (MCh), in an attempt to increase UNDW sensitivity and to establish standard testing protocols. In addition, results from UNDW challenges were compared to responses to inhalation of jet-nebulized distilled water (JNDW) and cold air (CACh). Compared to MCh, the sensitivity of continuously or intermittently (iUNDW) inhaled UNDW was 67 percent or 75 percent, respectively, when a positive response was defined by a greater than or equal to 20 percent fall in FEV1, but was higher when definition of a positive response was based on results from flow volume curves. Sensitivity of continuous or intermittent inhalation of JNDW was lower than for UNDW. The UNDW inhalations were better tolerated than CACh. Following stepwise iUNDW challenge, there was a clear reaction plateau for all variables measured. Results indicate that testing protocols with iUNDW inhalations over 6 to 10 min (corresponding to 7 to 11 ml water inhalation) yield the maximum sensitivity attainable with UNDW challenges, and require a minimum of patient and investigator effort. PMID- 1516398 TI - Histamine challenge in young children using computerized lung sounds analysis. AB - The use of the histamine challenge test (HCT) for the diagnosis of asthma has so far been limited to older children who can perform spirometry consistently. Recently, wheeze detection by tracheal auscultation with analog recording into a tape recorder has been utilized in young children in place of spirometry. Wheezing can also be identified using computerized lung sounds analysis (LSA) by a typical pattern on spectral analysis. Our aim was to develop a practical computerized system in which the response to histamine could be identified in an objective manner and documented on hard copy. Lung sounds were recorded with a Hewlett-Packard HP 21050A contact sensor placed over the right upper anterior chest. Sounds were amplified, band-filtered (50 to 2,000 Hz), and digitized at a sampling rate of 5.5 kHz into a Macintosh SE computer, and spectral LSA was performed. To validate our method, six older children (ages 9 to 16 years) with mild or moderate asthma underwent HCT. The identification of typical wheezing pattern (discrete, high-amplitude power peaks) on LSA was compared to 20 percent fall in FEV1 (PC20) and symptoms (cough, wheeze, chest tightness). In five children, the histamine concentration required to produce the characteristic wheezing pattern on LSA was half that required to produce a 20 percent fall in FEV1. In the sixth patient, wheezing on LSA and PC20 occurred at the same histamine concentration. To determine the technique's applicability to young children, we then studied six young asthmatic children (age 2 to 5 years). All children showed the wheezing pattern at a histamine concentration of 25 percent or 50 percent (one or two steps prior) to that producing symptoms (cough, wheeze, chest tightness) or wheezing on tracheal auscultation. Six age- and sex-matched nonasthmatic children (control subjects) did not show this pattern on LSA and had no symptoms or tracheal wheeze with HCT. We describe a sensitive method enabling application of HCT to young children who are unable to perform spirometry. This method is as sensitive as, and often more sensitive than, conventional PC20 with spirometry or tracheal auscultation. PMID- 1516399 TI - Determinants of airway response to challenge with distilled water in a population sample of children aged 7 to 10 years old. AB - We challenged 446 schoolchildren and measured the percent decrease in FEV1 following 10 min of tidal inhalation of UNDW. Assessment tools for respiratory symptoms and atopy were questionnaire and skin testing, respectively. A previous diagnosis of asthma was most strongly associated with a positive airway response (defined as a fall in FEV1 greater than or equal to 10 percent. A positive response was also associated with atopy, presence of cough, cough during night, or any respiratory symptom. A child's age and the prechallenge FEF75% also explained response to distilled water indicating less responsiveness for older children and those with relative greater airway diameter. For the previous diagnosis of asthma, a positive distilled water challenge test had a sensitivity of 36 percent and a specificity of 92 percent. We conclude that a significant relationship between airway response to distilled water, asthma and symptoms suggestive for asthma exists for a childhood population sample. PMID- 1516400 TI - The amplitude of circadian FEV1 variation suitable for phase determination by cosinor analysis in stable asthmatic children. AB - To elucidate the criterion for amplitude of circadian FEV1 variation suitable for phase analysis, six FEV1 measurements within a day were made on 346 days in 125 stable asthmatic children aged 8 to 12 years. Since coefficient of variation (CV) of FEV1 within a day in nonasthmatic children in our laboratory is less than 5 percent, circadian FEV1 variations were divided into CV greater than or equal to 5 percent and CV less than 5 percent groups. Forty-two (12 percent) variations with significant fit of cosinor rhythm were CV greater than or equal to 5 percent. Troughs in 32 (76 percent) variations of the 42 were distributed between 12 PM and 6 AM, and the deviation was highly significant against a uniform distribution (p less than 0.001). This was consistent with nocturnal asthma. Thirty-five (10 percent) variations with significant fit of cosinor rhythm were CV less than 5 percent. Troughs in 12 (34 percent) variations of the 35 were distributed between 12 PM and 6 AM, and the deviation from a uniform distribution was nonsignificant. These suggest that 5 percent or more of CV of FEV1 may be clinically suitable for analysis of circadian FEV1 variation. PMID- 1516401 TI - Repeated methacholine challenge produces tolerance in normal but not in asthmatic subjects. AB - Repeated methacholine challenge in normal nonasthmatic subjects (who require higher doses of methacholine than do asthmatic subjects to produce a 20 percent decrease in FEV1) can produce progressively diminishing methacholine responsiveness (or tolerance) with serial challenges. To determine whether tolerance to methacholine occurs in asthmatic subjects as it does in nonasthmatic subjects, we studied eight young (mean age, 24 years) mild asthmatic patients (occasional but not regular use of bronchodilator medications, PC20 methacholine range 0.1 to 7.0 mg/ml) who underwent five sequential methacholine challenges at 1.5-h intervals. Serially increasing concentrations of methacholine were given until FEV1 fell by 20 percent. Results were compared with those in seven nonasthmatic control subjects who underwent an identical protocol. As seen in previous studies, the normal subjects demonstrated significant tolerance to methacholine when each of five challenges was compared to the first. By contrast, in the asthmatic group, the mean cumulative dose of methacholine producing a 20 percent fall in FEV1 in the fifth challenge was not significantly different from the dose required in the first challenge. These results indicate that marked tolerance to methacholine does not occur in mild asthmatic patients with multiple repeated challenges over 6 h. The lower cumulative dose of methacholine required by asthmatic patients may be insufficient to produce tolerance. PMID- 1516402 TI - Currarino-Silverman syndrome (pectus carinatum type 2 deformity) and mitral valve disease. AB - Currarino-Silverman syndrome is a rare disorder characterized by premature fusion of manubrio-sternal joint and the sternal segments, resulting in a high carinate chest deformity; it is frequently associated with congenital heart disease. Among the various heart lesions reported in this syndrome, mitral valve disease and coarctation of the aorta have not yet been described (to our knowledge). Our report consists of five children with this syndrome, four of whom had mitral valve disease, with an associated coarctation of the aorta in one patient. The fifth patient had an innocent heart murmur. PMID- 1516403 TI - Idiopathic hypertrophic cardiomyopathy in identical twins. Morphological heterogeneity of the left ventricle. AB - We report a pair of identical twins with HC with varying extent of left ventricular hypertrophy and some degree of left ventricular outflow tract obstruction. The diagnosis of identical twins was based on the same sex, blood typings, HLA typings and hybridization patterns to four hypervariable DNA probes. Identical twins are derived from a single zygote and are genetically homogeneous human beings. The present report suggests that heterogeneity in the morphologic expression of HC may not be solely attributed to genetic factors. Environmental factors also may play an important role. PMID- 1516404 TI - Enhancement of theophylline clearance by oral albuterol. AB - The possible effect of albuterol on theophylline clearance was studied in ten adult volunteers. Subjects received intravenous aminophylline loading dose (5.6 mg/kg), with oral albuterol (4 mg every 6 h), or inhaled albuterol (200 micrograms every 6 h), or alone (control). Theophylline levels were determined for 12-h periods. Theophylline clearance and elimination t 1/2 were calculated. Theophylline clearance was significantly higher when given with oral albuterol, in comparison with control (0.83 +/- 0.05 vs 0.73 +/- 0.06 ml/kg/min, p less than 0.02). Theophylline elimination t 1/2 was shorter with the coadministration of oral albuterol, compared with control (7.1 +/- 0.3 vs. 8.1 +/- 0.6 h, p less than 0.02). These alterations in theophylline clearance and elimination were greater in subjects who had lower control theophylline clearance. Theophylline clearance and elimination t 1/2 recorded with inhaled albuterol were not significantly different from control values. Coadministration of oral albuterol and theophylline resulted in enhancement of theophylline clearance, particularly in subjects with initially slow theophylline elimination. Such patients may require theophylline dosage adjustment as a result of this interaction. PMID- 1516405 TI - Multidrug resistant Mycobacterium tuberculosis in patients with human immunodeficiency virus infection. AB - Multidrug resistant Mycobacterium tuberculosis (MDR-MTB) infection has not been recognized as a serious problem in patients with human immunodeficiency virus (HIV) infection. Multidrug resistance (MDR) has appeared in our medical center in 24 out of 72 patients between January 1990 and May 1991 compared to 8 out of 132 patients within the period from 1982 to 1987 (relative risk 5.50 with 95 percent confidence interval 2.61 to 11.61). We describe 19 patients with MDR in MTB (isoniazid and at least one additional first line drug), who had serologic evidence of HIV infection, 13 of whom were diagnosed with acquired immunodeficiency syndrome (AIDS). The MTB cultures from 10 out of 19 patients with MDR were resistant to three or more drugs. Fifteen patients died although 9 out of these 15 had received at least a four-drug regimen for a mean time of seven weeks (range 2 to 12). This increase in MDR was seen in ten homosexuals and nine intravenous drug users. This rapid appearance of MDR-MTB strains is worrisome. New strategies for empiric therapy of such patients while awaiting sensitivity data are needed. PMID- 1516406 TI - Homeless individuals and drug-resistant tuberculosis in south Texas. AB - Drug-resistant tuberculosis was found in 21 percent of homeless individuals in New York City between 1982 and 1987. To see if this relationship existed in south Texas, we evaluated all admissions to a Texas Health Department facility with culture-proven tuberculosis. Four hundred forty-three patients were admitted between September 1987 and October 1990. Twenty-six, (5.9 percent) of these patients were identified as homeless. Alcoholism, tobacco abuse, divorce, and unemployment were common demographic characteristics. Six male patients and one female patient (27 percent) had Mycobacterium tuberculosis resistant to one or more antituberculosis drugs. Five were Hispanic, one was white, and one was black. The six male patients had resistance to only one drug, either rifampin or ethambutol. The female patient had resistance to streptomycin, isoniazid, and rifampin. These findings illustrate that drug-resistant tuberculosis exists among homeless individuals in south Texas. As the number of homeless people increases, physicians need to recognize that pulmonary tuberculosis is a frequent infection in this population and that the causal mycobacteria may well be resistant to one or more antituberculosis agents. PMID- 1516407 TI - Measurement of lung density by means of quantitative CT scanning. A study of correlations with pulmonary function tests. AB - In recent years, much attention has been given to the role of CT in detecting and quantitating pulmonary emphysema. We measured CT lung density in 45 patients undergoing a diagnostic work-up and compared this with pulmonary function tests. The CT lung densities measured with the sector method and with the whole lung method were very highly correlated with each other (r = 0.96, p less than 0.001), and measurements at TLC systematically gave a lower density than those at FRC (p less than 0.001). Also, CT density measurements at TLC and even more so at FRC correlated well with pulmonary function indices of airway obstruction and of hyperinflation, but not with indices that are considered more specific for emphysema (single breath DCO, static lung compliance) We conclude that CT lung density gives a good reflection of the degree of hyperinflation, ie, enlargement of distal airways, but is not sensitive to detect whether or not this is associated with emphysema. PMID- 1516408 TI - Migration of neutrophils from the lung into the pleural space after lung resection in humans and rabbits. AB - The origin of neutrophils that are found in pleural effusions after pulmonary resection is unknown. We measured neutrophil counts in pleural effusion sequentially for 48 h in patients who had undergone partial resection or pneumonectomy. Additionally, we measured neutrophil counts in the pleural effusions separately from the visceral pleura and parietal pleura in rabbits. In humans, we found that the maximum neutrophil counts in pleural effusion occurred more often in the patients who underwent partial resection (11.7 +/- 6.0 x 10(4) cells/microL) than in the patients who underwent pneumonectomy (3.7 +/- 1.2 x 10(4) cells/microL). There was no difference between neutrophil counts in blood of pneumonectomy group and that of the partial resection group. In rabbits, neutrophil counts were 1.5 times greater in the pleural effusion derived from the lung than in that derived from the parietal pleura. We conclude that movement of neutrophils occurs primarily from the lung into the pleural space after lung resection in humans and rabbits. PMID- 1516409 TI - Effects of inhaled platelet activating factor on bronchial responsiveness in patients with symptomatic and asymptomatic pulmonary embolism. AB - To determine the possible role of platelet-activating factor (PAF) in pulmonary embolism (PE), the reactivity of the airways to inhaled PAF, using doses ranging from 6.25 to 400 micrograms, was examined in 24 patients with a past episode of PE. Twelve of these patients had experienced acute respiratory insufficiency during the episode (with or without additional symptoms). None of the remaining 12 patients had experienced any respiratory symptoms during the PE episode. Diagnosis was established by means of a ventilation-perfusion lung scan performed when admitted to the hospital because of deep venous thrombosis (DVT) in the lower limbs. Nonspecific bronchial reactivity as measured by the response to bronchoprovocation testing with methacholine showed no significant differences between both groups. PAF caused a dose-dependent bronchoconstriction defined by at least a 35 percent decrease in specific airway conductance (SGaw) in all patients. The average dose of PAF needed to decrease SGaw 35 percent was significantly lower in patients who had had a symptomatic PE than in those with asymptomatic PE (p = 0.011). This finding suggests that patients who suffered from symptomatic PE may present a greater airway reactivity to inhaled PAF. This different behavior might explain the existence of some of the respiratory symptoms of PE, which could be attributed to PAF-related effects. However, additional studies are needed to evaluate the role of PAF in PE. PMID- 1516410 TI - Breathlessness in patients with severe chronic airflow limitation. Physiologic correlations. AB - We wished to identify the physiologic abnormalities that distinguish severely breathless (SB) patients with chronic airflow limitation (CAL) from mildly breathless (MB) patients. Thirty-seven patients with stable, advanced CAL (FEV1 = 38 +/- 10 percent predicted, mean +/- SD) were separated into two distinct groups, SB and MB, solely on the basis of their baseline dyspnea index (BDI). BDI ratings in SB (n = 17) and MB (n = 20) patients were 2.5 +/- 1.5 and 8.5 +/- 1.5 (mean +/- SD), respectively (p less than 0.001). Groups were compared with respect to pulmonary function, breathing pattern parameters, arterial blood gases (ABGs), and responses to progressive exercise. Steady-state gas-exchange parameters were measured in a subgroup of 16 patients during exercise. There were no significant intergroup differences in dynamic flows, plethysmographic lung volumes, ABGs, resting ventilation, or breathing pattern parameters. However, the SB group had significantly lower single-breath diffusing capacities for carbon monoxide (Dco) (by an average of 50 percent, p less than 0.001), together with significantly higher resting ventilatory equivalents for carbon dioxide (VE/VCO2) (by 17 percent, p less than 0.01) and dead space to tidal volume ratios (by 11 percent, p less than 0.05). Ventilatory responses for a given metabolic load were, on average, 33 percent higher (p less than 0.05) in the SB group reflecting greater ventilation-perfusion inhomogeneity and wasted ventilation. The SB subgroup (n = 7), in contrast to the MB subgroup (n = 9), demonstrated significantly (p less than 0.01) greater O2 desaturation during exercise; PaO2 decreased in SB and MB at peak exercise by -13 +/- 7 mm Hg and -4 +/- 2 mm Hg (mean +/- SD), respectively. Stepwise regression analysis selected DCO and VE/VCO2 as the only predictors of breathlessness in this group, accounting for 52 percent of the variance in BDI (F-ratio = 18.49, p less than 0.001). Although the origin of breathlessness is multifactorial, variation in its intensity among patients with comparable levels of airflow limitation can be accounted for, in part, by underlying pathophysiologic differences. Severely breathless patients were characterized by lower resting diffusing capacities and accelerated ventilatory responses to exercise. PMID- 1516411 TI - Proliferative characteristics of fibroblast lines derived from open lung biopsy specimens of patients with IPF (UIP). AB - We compared the doubling time of fibroblasts derived from idiopathic pulmonary fibrosis (usual interstitial pneumonia) (IPF [UIP]) lung tissues and control fibroblasts, cultured in usual growth medium, and examined the response of these fibroblasts to platelet-derived growth factor (PDGF) and prostaglandin E2 (PGE2). Ten fibroblast lines from open lung biopsy specimens of patients with IPF (UIP) and ten control fibroblast lines from surgically resected lung tissue of patients with limited lung diseases were established. The average doubling time of fibroblast lines was 32.0 +/- 6.0 h (mean +/- SD) in UIP and 33.2 +/- 10.4 h in controls, showing no difference between the two groups. To examine the responses of fibroblasts to PDGF and PGE2 and the differences between fibroblasts derived from fibrotic tissues with different intensity of fibrosis, lung specimens from five patients with IPF were subdivided into two groups, higher-intensity fibrotic lesions (H) and lower-intensity fibrotic lesions (L). The fibroblast lines were established separately. 3H-thymidine uptake with or without PDGF or PGE2 was examined. Results were expressed as the index of thymidine incorporation into the fibroblasts. There were no differences in the doubling times and the responses to PDGF and PGE2 between H and L. There were no differences between control and H regarding their response to PDGF. In response to PGE2, the growth inhibition for H was significantly decreased compared with the control (p less than 0.05). There was no difference in growth inhibition between H and L. The finding that PGE2 inhibits fibroblast proliferation less in UIP lung tissue suggests that fibroblasts from UIP were functionally altered cells or, to some extent, out of normal regulation. These results suggest an abnormal proliferation of fibroblasts observed in IPF (UIP). PMID- 1516412 TI - Abnormal oxygen uptake responses to exercise in patients with mild pulmonary sarcoidosis. AB - Exercise intolerance and exertional dyspnea are common complaints in patients with sarcoidosis. Although in many cases these complaints are attributable to restrictive or obstructive lung mechanics or inefficiency of pulmonary gas exchange, other processes also may contribute to impairment in exercise function and may not be readily detected or distinguished from problems of lung mechanics on the basis of symptoms or routine laboratory testing. To identify the frequency and etiology of impaired exercise capacity in sarcoidosis patients with mild lung disease, integrative cardiopulmonary exercise testing was performed in 23 patients. Breath-by-breath measurements were made of gas exchange, ventilation, and heart rate. In 9 of 20 evaluable patients, the oxygen uptake (VO2) at the anaerobic threshold was low, and/or the rate of increase of VO2 was abnormal relative to work rate or heart rate, suggesting a defect in cardiocirculatory function. Resting and exercise echocardiography revealed normal left ventricular ejection fractions and wall motion in all nine of these patients, but findings suggestive of right ventricular hypertrophy and/or right ventricular dysfunction were present in five. Abnormal responses of VO2 during exercise are common in patients with sarcoidosis and may be due to subclinical impairment of right-sided cardiac function. PMID- 1516413 TI - Nocturnal nasal IPPV stabilizes patients with cystic fibrosis and hypercapnic respiratory failure. AB - Nocturnal nasal intermittent positive pressure ventilation (nIPPV) has been used successfully in the management of patients with respiratory failure due to chest wall deformity and neuromuscular disease. In order to determine if nIPPV is useful in patients with cystic fibrosis (CF) complicated by respiratory failure, we treated four hypercapnic patients for up to 18 months. All patients had failed to respond to intensive conventional therapy, including nocturnal nasal CPAP in three of the patients. Within a few days of commencing nIPPV, all reported improved length and quality of sleep. There was lessening of the degree of hypercapnia and an increase in respiratory muscle strength. After stabilization in the hospital, all patients were able to be discharged home receiving nocturnal assisted ventilation. The improvements seen in these patients have been maintained for up to 18 months. We believe nIPPV offers an effective therapeutic approach for patients with end-stage CF in hypercapnic respiratory failure and may be particularly advantageous for those awaiting heart-lung transplant. PMID- 1516414 TI - Pulmonary dirofilariasis. The largest single-hospital experience. AB - Pulmonary dirofilariasis caused by Dirofilaria immitis, the dog heartworm, is a rarely reported pulmonary lesion. It most often appears as a solitary pulmonary nodule, often mistaken for a primary or metastatic lung tumor, and the diagnosis is not often established until thoracotomy with excisional lung biopsy is performed. Sporadic reports of pulmonary dirofilariasis in the United States total only 87 cases. The ten resections of pulmonary dirofilariasis at the Methodist Hospital in Houston, Tex, represent the largest reported series of cases originating at a single hospital. We present an overview of the pathogenesis of this disease, its clinical manifestations and epidemiologic features. The prevalence of pulmonary dirofilariasis appears to be increasing. Thus, surgeons and pathologists need to be aware of this etiology of granulomatous pulmonary lesions. PMID- 1516415 TI - Indomethacin and methacholine tolerance in normal subjects. Role of prostaglandin synthesis in the attenuation of methacholine's effect during repeated inhalation challenges. AB - Within hours, tolerance occurs to repeated methacholine challenge in normal subjects, and this study examines whether prostaglandin synthesis produces this phenomenon. On two separate study days, ten nonasthmatic non-smoking subjects with measurable baseline responsiveness to methacholine performed five sequential methacholine challenge tests over 6 h. Pretreatment before each day consisted of either placebo tablets or 50-mg tablets of indomethacin given three times daily for 48 h prior to testing. Medications were administered in a single-blind crossover fashion, with study days assigned in random order and separated by at least 1 wk. Methacholine challenge tests were summarized by the PD20FEV1 (the provocative dose in cumulative breath units [cbu] required to produce a 20 percent fall in FEV1). Indomethacin pretreatment had no effect on baseline spirometry between the two study days; however, the baseline geometric mean PD20FEV1 fell from 145 +/- 2 cbu (+/- percent SD) after placebo pretreatment to 65 +/- 1 cbu (+/- percent SD) on the indomethacin day (p = 0.046). This effect of indomethacin on baseline airway responsiveness persisted when an additional ten subjects were studied to further investigate this finding. Significant tolerance to repeated methacholine challenges occurred on both study days, with geometric mean PD20FEV1 rising approximately 16-fold (p less than 0.0001) regardless of pretreatment received. This study demonstrates that the attenuation of methacholine's effect with repeated testing is not due solely to prostaglandin synthesis and must involve, in part, other mechanisms, such as changes in methacholine deposition, agonist-receptor interactions, or postreceptor responses. In addition, prostaglandin inhibitors may increase baseline methacholine responsiveness in healthy nonasthmatic subjects. PMID- 1516416 TI - Small airways dysfunction in systemic sclerosis. A controlled study. AB - A debate exists regarding the importance of small airways disease in systemic sclerosis, while smoking seems to have a major effect on the exact prevalence. In order to evaluate small airways dysfunction (SAD) in a pure systemic sclerosis population, we performed pulmonary function studies in 31 nonsmoking patients and 31 age- and sex-matched nonsmoking control subjects. Patients' FVC, TLC, and Dco mean values were significantly lower compared with the corresponding values of the controls (p less than 0.05), while there was no difference in MEF25, RV, and RV/TLC. Seven (22.6 percent) of 31 patients and four controls (a nonsignificant difference) had evidence of SAD, namely a maximum expiratory flow at 25 percent of vital capacity (MEF25) less than 60 percent of predicted. Positive correlation (p less than 0.001) was found between MEF25 and FEV1/FVC in the patients. Moreover, no differences were found in abnormal lung function patients with and those without SAD in demographic, clinical, roentgenologic, and serologic features and results of pulmonary function tests. These findings suggest that SAD in our patients is not a characteristic and early manifestation of systemic sclerosis and that, when present, it is not correlated with the severity of the pulmonary involvement in scleroderma. PMID- 1516417 TI - Impairment of lung mucociliary clearance in pigeon fanciers. AB - Lung mucociliary clearance was measured in 15 pigeon fanciers. The study group was subdivided into two: a precipitin-positive group (n = 10; mean +/- SEM age 45 +/- 5 years) with circulating blood precipitins and a precipitin-negative group (n = 5; mean +/- SEM age 40 +/- 3 years) without. Clearance was measured using an objective, noninvasive radioaerosol technique. The data for both groups were compared with those of matched control groups of healthy subjects. The mean +/- SEM area under the tracheobronchial retention curves (AUC) over the 6-h observation period was 257 +/- 27 %h for the precipitin-positive group compared with 177 +/- 16 %h for its control group (p = 0.02)--a high AUC value denoting slow clearance. That for the precipitin-negative group was 282 +/- 34 %h compared with 150 +/- 15 %h for its control group (p = 0.02). Our study illustrates in pigeon fanciers involvement of the conducting airways in that a major defense mechanism of the airways--namely, mucociliary clearance--is substantially compromised. The presence or absence of precipitins appears not to be related to the degree of mucociliary clearance impairment. PMID- 1516418 TI - Corticosteroids for Pneumocystis carinii pneumonia with acute respiratory failure. Experience with rescue therapy. AB - Corticosteroids have proven effective as adjunctive therapy for the treatment of PCP in patients with AIDS, when begun within 72 h of conventional anti Pneumocystis therapy. Their efficacy as rescue (or salvage) therapy in patients who have failed conventional therapy, however, remains unproven. Ths report presents our experience with 16 patients admitted to our MICU for acute respiratory failure (PaO2/FIO2 ratio less than or equal to 150) due to PCP. Five of six patients (83 percent) who received "primary" CS rescue (initial CS use prompted by acute respiratory failure after 72 h of conventional anti Pneumocystis therapy) survived hospitalization. Our experience suggests that CSs may be effective even when started after 72 h of conventional therapy. Additional studies are needed to clarify the role of CS rescue therapy. PMID- 1516419 TI - A comparison of three pulmonary artery oximetry catheters in intensive care unit patients. AB - OBJECTIVE: To compare the clinical performance of three pulmonary artery oximetry catheters (Oximetrix 3, SAT-2, and HEMOPRO2) in intensive care unit (ICU) patients. DESIGN: Unblinded comparison of performance over 24 h using an IL-282 CO-oximeter as a criterion standard. SETTING: Multispecialty adult ICU at a university teaching hospital. PATIENTS: Thirty critically ill patients selected from those requiring hemodynamic monitoring for medical management. MEASUREMENTS AND MAIN RESULTS: By all measures, performance of the Oximetrix 3 and SAT-2 systems were comparable; bias +/- precision were -1.98 +/- 3.07 and +1.80 +/- 3.49, respectively, vs -2.28 +/- 5.24 for the HEMOPRO2. The Oximetrix 3 and SAT-2 systems demonstrated consistent performance over the range of saturations tested, though Oximetrix 3 tended to underestimate and SAT-2 tended to overestimate the CO-oximeter value. The HEMOPRO2 underestimated the CO-oximetry-derived saturation, although this was not constant across the range of values tested. The 95 percent confidence limits based on intrasubject variability were similar (+/- 4.59, +/- 5.66, and +/- 6.56 for the Oximetrix 3, SAT-2, and HEMOPRO2, respectively); however, the 95 percent confidence limits based on total variability, while similar for Oximetrix 3 (+/- 6.03) and SAT-2 (+/- 6.86), were larger for the HEMOPRO2 (+/- 10.30). The expected SD was similar for the three systems (2.03, 2.50, and 2.90 for the Oximetrix 3, SAT-2, and HEMOPRO2 systems, respectively). None of the systems equaled or exceeded (p greater than 0.05) the manufacturers' published specifications, which, in all cases, are listed as +/- 2 percent (saturation; 1 SD) when compared with bench oximetry. CONCLUSIONS: Although each system measures mixed venous oxygen saturation, the Oximetrix 3 and SAT-2 systems demonstrate closer agreement with CO-oximetry. However, none of these catheters provided statistically significant evidence that they would perform within +/- 2 percent of CO-oximetry. As a continuous monitor used to detect changes or trends, any of the three may be acceptable. PMID- 1516420 TI - Relationship of oxygen consumption and oxygen delivery in surgical patients with ARDS. AB - Previous studies have described oxygen delivery (DO2) and oxygen consumption (VO2) relationships in patients with ARDS and other acute diseases that suggest occasions when VO2 may be dependent on the supply of oxygen, ie, DO2. We studied 127 postoperative patients who developed ARDS to evaluate the relationship of DO2 to VO2. We found a weak correlation between DO2 and VO2 in the total series (r = 0.49) as well as in several clinical subgroups of patients with ARDS. Moreover, we observed similar relationships in a concurrent group of 218 postoperative patients who did not develop ARDS. We also examined the DO2/VO2 data of individual patients with ARDS to identify instances where flow-dependent VO2 patterns developed into flow-independent VO2 patterns. We were able to identify an apparent plateau in the DO2/VO2 relationships in 29/50 (58 percent) patients where multiple measurements were obtained over a short period of time. Our data are consistent with the concept that the DO2/VO2 relationship in acutely ill early postoperative patients with and without ARDS is affected by antecedent circulatory problems that may lead to tissue hypoxia and tissue oxygen deficiencies that are manifest by flow dependency. PMID- 1516421 TI - Nasal mask ventilation in acute respiratory failure. Experience in elderly patients. AB - Nasal mask ventilation (NMV) has been used successfully in chronic restrictive respiratory failure and more recently in acute exacerbations of chronic obstructive pulmonary disease (COPD). This study aimed to evaluate the possible role of NMV in acute respiratory failure (ARF) episodes when mechanical ventilation with endotracheal intubation is questionable. Thirty patients (age, 76 +/- 8.1 years) were treated by NMV during ARF episodes (COPD, 20; other chronic respiratory failure [CRF], 5; chronic heart failure [CHF], 4). All patients were hypoxemic (PaO2, 5.85 +/- 1.62 kPa) and hypercapnic (PaCO2, 8.63 +/ 1.89 kPa) with respiratory acidosis (pH, 7.29 +/- 0.08). In all cases, clinical or physiologic parameters indicated the need for mechanical ventilation, but endotracheal intubation was either not applied because of the age and the physiologic condition of the patients (17 cases) or was postponed (13 cases). NMV was performed using a volume-cycled ventilator and a customized nasal mask. Ventilation was continuous during the first 12 hours and the following nights and was then intermittent during the day. Twenty-one patients improved clinically, within a few hours. Progressive correction of arterial blood gases was observed: PaO2 increased during the first hour, but PaCO2 decreased more slowly. Eighteen patients were able to be successfully weaned from NMV. Twelve patients failed to improve despite NMV: eight of them died and four required endotracheal intubation. There was no difference in the success rate between patients in whom endotracheal ventilation was contraindicated or postponed. Clinical tolerance was satisfactory in 23 patients and poor in seven patients. A return to the respiratory condition was observed in the surviving patients with subsequent discharge from hospital. NMV therefore successfully treated respiratory distress initially in 60 percent of the 30 patients. These results suggest that NMV could be a possible alternative in the treatment of ARF, even in very ill patients, when endotracheal ventilation is controversial or not immediately required. PMID- 1516422 TI - An interrupter technique for measuring respiratory mechanics and the pressure generated by respiratory muscles during partial ventilatory support. AB - We evaluated the airway occlusion maneuver as a method to estimate respiratory resistance, respiratory elastance and the pressure generated by respiratory muscles in ICU patients breathing in the PSV mode. The airflow was interrupted at selected flows or volumes during inspiration by a computer-driven rapid occlusion pneumatic valve. The airway occlusion was maintained for 2 to 3 s. From the airway pressure tracing we obtained various measurements of pressure. We then computed the pressure generated by the patient's inspiratory muscles. The method was validated by two different approaches in two groups of patients: the Pes and the CMV protocols. We conclude that the airflow interruption method can be used to measure basic respiratory mechanical parameters in PSV patients. The method also offers an opportunity to evaluate Pmusc,aw and the respiratory work performed by the patient. PMID- 1516423 TI - Evaluation of a reservoir device for metered-dose bronchodilator delivery to intubated adults. An in vitro study. AB - We investigated the use of a reservoir device for delivery of a MDI bronchodilator aerosol using a lung model of an intubated, mechanically ventilated adult. METHODS: Albuterol (Proventil) was delivered with a MDI using three methods. In method 1, the MDI was attached directly onto the ETT using a commercially available actuator/adapter. In method 2, the Monaghan AeroVent reservoir was placed on the inspiratory limb of the ventilator circuit just before the patient Y connector. In method 3, the AeroVent was placed between the patient Y connector and the ETT. Standardized ventilator settings with a Servo 900C were used for all three methods (VE = 9.6 L; respiratory rate = 12 breaths per minute; TI = 20 percent of 1 s). Aerosol drug delivery was measured at the distal tip of the ETT using a spectrophotometric technique. Percentage of amount delivered was calculated from measured delivery of the MDI. RESULTS: The MDI directly on the ETT delivered 7.3 percent of the total dose to the end of the ETT. The AeroVent on the inspiratory limb increased this to 32.1 percent and the AeroVent between the Y connector and the ETT delivered 29 percent. Both reservoir delivery methods delivered significantly more drug than direct placement of the MDI on the ETT (p less than 0.01) but did not differ from each other (p greater than 0.05). CONCLUSIONS: Use of the AeroVent reservoir chamber significantly increased bronchodilator delivery by aerosol with an MDI in an adult lung model of an intubated patient on ventilatory support. PMID- 1516424 TI - The effects of cromolyn sodium in dogs undergoing high-frequency oscillation superimposed on conventional mechanical ventilation. AB - The effects on gas exchange of superimposition of high-frequency oscillation (HFO) (40 Hz) on conventional mechanical ventilation were investigated in mongrel dogs with eucapnic gas exchange on conventional mechanical ventilation (CMV). The dogs were anesthetized, paralyzed, and ventilated with CMV until stable. Oscillation was then superimposed for 15 min, followed by CMV alone for a further 30 min. During HFO superimposed on CMV (CMV-HFO), the arterial carbon dioxide tension (PaCO2) increased from 43.6 +/- 1.2 mm Hg to 47.2 +/- 1.4 mm Hg (p less than 0.02), whereas the arterial oxygen tension (PaO2) did not change at all. The change was inhibited completely by administration of intravenous cromolyn sodium (CS) (6 mg/kg/min). The mean pulmonary arterial pressure (mPAP), cardiac output (CO), pulmonary capillary wedge pressure (PCWP), and pulmonary vascular resistance (PVR) did not change during the experiment. These results demonstrate that CMV-HFO appears to cause CO2 accumulation and eliminates the impaired O2 transfer, and that these effects are inhibited completely by CS administration. PMID- 1516425 TI - A subtle chest radiographic finding. Where is the pathology? PMID- 1516426 TI - Pulmonary venous infarction. AB - Pulmonary venous infarction, although rare, can develop in patients with the various pathologic conditions outlined. The triad of cough, dyspnea, and hemoptysis should raise clinical suspicion. The venous phase of pulmonary arteriography is the best way to document pulmonary venous obstruction, although MR imaging may also prove useful in the future. Treatment of patients with pulmonary venous infarction should be determined on the basis of the obstructing pathologic findings. Antibiotic therapy is important, as evidenced by the early experimental experience with this condition. It may be the only treatment available to patients with idiopathic fibrosing mediastinitis. Pulmonary resection, however, can be accomplished when a localized obstructing lesion is identified. PMID- 1516427 TI - High-resolution computed tomography in the diagnosis of miliary tuberculosis. PMID- 1516428 TI - Diverse roentgenographic manifestations of the rare pulmonary involvement in myeloma. AB - Roentgenographic manifestations of two cases of pulmonary involvement with myeloma were presented. One showed a nodular mass lesion extending from an extramedullary mediastinal plasmacytoma into the lung parenchyma while the other showed diffuse reticulonodular infiltrate by myeloma cells in association with alveolar septal amyloidosis. These two cases demonstrate the extreme variability of pulmonary involvement by myeloma, which can mimic a solitary tumor or an inflammatory infiltrate. PMID- 1516429 TI - Lung transplantation in a patient with a prior bone marrow transplant. AB - A 25-year-old woman with acute lymphoblastic leukemia underwent two bone marrow transplants. She subsequently developed severe restrictive lung disease which was successfully treated with a single lung transplant. PMID- 1516430 TI - Pulmonary venous infarction secondary to squamous cell carcinoma. AB - This type of pulmonary venous infarction has not been previously reported, namely: pulmonary vein obstruction from squamous cell carcinoma. Furthermore, this case is unique in that the characteristic pathologic vascular changes observed with pulmonary venous infarction were contrasted with a noninfarcted upper lobe that was removed from the same patient one year later. PMID- 1516431 TI - Candida albicans purulent pericarditis treated successfully without surgical drainage. AB - Cures of Candida pericarditis reported in the literature uniformly involved surgical drainage of the pericardial space. We report a patient with purulent pericarditis caused by Candida albicans who was treated successfully with antifungal chemotherapy combined with a single pericardiocentesis that did not completely evacuate the pericardial space. This case indicates that thoracotomy with surgical drainage of the pericardium is not mandatory for successful therapy of Candida pericarditis. PMID- 1516432 TI - Nonbacterial thrombotic endocarditis. Assessment by transesophageal echocardiography. AB - Nonbacterial thrombotic endocarditis (NBTE) is difficult to detect antemortem and is often not suspected until embolic events occur. Transthoracic echocardiography is useful in diagnosing NBTE, but it may be limited by suboptimal imaging and resolution. Herein we describe the first reported case of NBTE diagnosed by transesophageal echocardiography. As early detection and treatment may avert significant embolic complications, transesophageal echocardiography should be strongly considered if other techniques are nondiagnostic and clinical suspicion of NBTE remains high. PMID- 1516433 TI - HIV-associated pericardial effusions. AB - Following a case of cardiac tamponade in a patient with the acquired immunodeficiency syndrome (AIDS), we examined the frequency and clinical spectrum of pericardial effusions associated with human immunodeficiency virus infection (HIV) at our institution. Of 187 hospitalized patients documented to have pericardial effusions over a one-year period, 14 (7 percent) were known to be HIV positive at the time of their echocardiograms. One patient presented with a large effusion and cardiac tamponade, three had moderate effusions, and ten had small effusions. The probable effusion etiology was established in four cases and included endocarditis (2), lymphoma (1), and myocardial infarction (1). In hospital mortality was 29 percent (4 of 14). From our study, as well as a growing number of reports in the literature, we conclude that HIV-associated pericardial effusions are frequently seen and that their clinical spectrum is broad. PMID- 1516434 TI - Treatment of life-threatening primary pulmonary hemosiderosis with cyclophosphamide. AB - This report describes a five-year-old boy with severe pulmonary hemorrhage caused by primary pulmonary hemosiderosis with cow's milk sensitivity. After failing to respond to corticosteroids and azathioprine, he dramatically improved after being given cyclophosphamide. He worsened after discontinuation of cyclophosphamide on two occasions and improved significantly with its reinstitution. Cyclophosphamide was continued for 14 months without further bleeding or adverse effects. The patient has remained in remission for nearly five years. Cyclophosphamide may be a life-saving alternative therapy for refractory pulmonary hemorrhage with pulmonary hemosiderosis. PMID- 1516435 TI - Implantable cardioverter defibrillator infection causing constrictive pericarditis. AB - A case of severe constrictive pericarditis resulting from an indolent Pseudomonas aeruginosa infection of the automatic internal cardiac defibrillator is described. Total explanation of the device was attempted after nine months but was unsuccessful because of dense adhesions under the patch electrodes. The patient subsequently developed clinical and hemodynamic findings of constrictive pericarditis and a second desperate attempt to remove the patches resulted in operative death. Diagnostic modalities for detecting infection of the AICD are reviewed. As soon as there is infection involving any component, the entire lead system and pulse generator should be removed. PMID- 1516436 TI - Tracheal sounds in upper airway obstruction. AB - A boy with subglottic narrowing secondary to laryngotracheitis presented with noisy breathing. Acoustic measurements of tracheal sounds at standardized air flows correlated well with the clinical course and with spirometric assessments. This indicates the potential value of respiratory sound characterization in patients with upper airway obstruction. PMID- 1516437 TI - Dangerous pencils and a new technique for removal of foreign bodies. AB - Aspirated foreign bodies are important problems during childhood. Some instances may be fatal. Most of the foreign bodies are removed with use of classic instruments like rigid bronchoscopes and foreign body forceps. But sometimes we fail to remove them, particularly aspirated beads and spherical objects. In this case, a Fogarty catheter is helpful. Although we have had many experiences recently we failed to remove one aspirated foreign body which was a pencil cap. We succeeded in removing this pencil cap with a new technique that is explained in this article. We used a Storz transbronchial aspiration biopsy needle and a cotton-carrier stylet to remove the pencil cap. PMID- 1516438 TI - Single lung transplantation for primary pulmonary hypertension without cardiopulmonary bypass. AB - We report the first case, to our knowledge, of single lung transplantation for primary pulmonary hypertension carried out without cardiopulmonary bypass. This operation seems to be possible even if the right ventricular ejection fraction is low (0.17) and the pulmonary vascular resistance very high (1,096 dynes.s.cm5). Since 1981, heart-lung transplantation has been successfully performed in patients with primary pulmonary hypertension. If heart-lung transplantation results in resolution of pulmonary hypertension, the incidence of obliterative bronchiolitis is significant in heart-lung transplantation recipients. Single lung transplantation has been performed for end-stage interstitial and obstructive lung disease but has not been considered a good option for primary pulmonary hypertension due to concerns that a single transplanted lung would be unable to cope with the entire blood flow. However, recently single lung transplantation has been performed for primary pulmonary hypertension, the risk of obliterative bronchiolitis remaining unknown. The purpose of this communication is to report one case of single lung transplantation for primary pulmonary hypertension and the feasibility of this operation without the use of cardiopulmonary bypass, if cardiopulmonary bypass is thought to be dangerous. PMID- 1516439 TI - Prolonged extracorporeal support for ARDS using surface-heparinized equipment. AB - Severely ill ARDS patients present major supportive challenges when conventional ventilatory support is failing. A patient is described who was treated with venovenous extracorporeal lung support for 28 days, using surface-heparinized circuitry. Her recovery illustrates the potential for salvage of near-terminal ARDS patients when complications of support can be minimized. PMID- 1516440 TI - Orthostatic and exercise-induced advanced nodal atrioventricular block. AB - A 69-year-old woman was referred for asthenia and dizziness when walking in the last two months. No clinical abnormalities were found, and sinus rhythm was present when lying down. On orthostatism and walking, advanced AV block developed. Atropine and isoproterenol ameliorated the AV conduction abnormality, suggesting a nodal block. The patient remained asymptomatic after pacemaker implantation. PMID- 1516441 TI - Polypoid endobronchial lesions. A manifestation of bacillary angiomatosis. AB - Polypoid endobronchial lesions occurred in a patient with acquired immunodeficiency syndrome (AIDS) with recent fever, skin lesions, lymphadenopathy, lung infiltrates, and pleural effusions. His condition improved with antimicrobials and vincristine. After therapy ceased, skin lesions recurred and gastroesophageal mucosal lesions developed. Bacillary angiomatosis was identified during retrospective analysis of skin and endobronchial biopsy specimens. PMID- 1516442 TI - Intralobar pulmonary sequestration presenting as congestive heart failure in a neonate. AB - We recently evaluated a premature infant with intralobar pulmonary sequestration which presented with signs of CHF. The infant initially underwent ligation of a PDA but subsequently developed tachycardia, tachypnea, and a continuous murmur which radiated to the back. The diagnosis of a pulmonary sequestration was suggested by Doppler echocardiography and confirmed by aortography. The sequestration was successfully treated by surgical removal of the involved lobe. PMID- 1516443 TI - Diagnostic value of pleural fluid cytology in occult Boerhaave's syndrome. AB - When Boerhaave's syndrome presents with atypical clinical features and eludes prompt diagnosis, delays in surgical therapy increase complications and mortality. We present a patient with occult Boerhaave's syndrome who had nondiagnostic esophageal contrast studies and thoracic computed tomography. Pleural fluid cytologic analysis established the presence of esophageal rupture by detecting undigested food particles. PMID- 1516444 TI - Incorrect use of metered-dose inhalers. PMID- 1516445 TI - Use of a heat and moisture exchanger during long-term mechanical ventilation. PMID- 1516446 TI - Postoperative acute respiratory distress syndrome. A complication of amiodarone associated with 100 percent oxygen ventilation. PMID- 1516447 TI - Diagnosis of entomophthoromycosis. PMID- 1516448 TI - An unusual cause of electrical alternans. PMID- 1516449 TI - Pulmonary lymphangioleiomyomatosis. PMID- 1516451 TI - Task Force on Research and Education for the Prevention and Control of Respiratory Diseases. Report and recommendations. PMID- 1516450 TI - Reactive airway disease after chlorine gas exposure. PMID- 1516452 TI - Asthma prevention. Task Force on Research and Education for the Prevention and Control of Respiratory Diseases. PMID- 1516453 TI - Pediatric lung diseases. Task Force on Research and Education for the Prevention and Control of Respiratory Diseases. PMID- 1516454 TI - Chronic obstructive pulmonary disease. Task Force on Research and Education for the Prevention and Control of Respiratory Diseases. PMID- 1516455 TI - Prevention of occupational lung disease. Task Force on Research and Education for the Prevention and Control of Respiratory Diseases. PMID- 1516456 TI - Smoking: epidemiology, cessation, and prevention. Task Force on Research and Education for the Prevention and Control of Respiratory Diseases. PMID- 1516457 TI - Clinical trial methodology in pediatric RTI. Preface. PMID- 1516458 TI - The threat of resistance to the new oral cephalosporins. AB - Phenotypic resistance to beta-lactam antibiotics is mainly due to the prevalence of beta-lactamases. The most common enzymes responsible for resistance to aminopenicillins and older (1st generation) cephalosporins are the TEM-1, TEM-2, OXA-1 and SHV-1 enzymes, all of which are plasmid-mediated. The recent development of oral cephalosporins sharing structural features and an antimicrobial spectrum comparable to that of 3rd-generation cephalosporins has provided highly active compounds for the management of outpatient infections. Two principal mechanisms, however, may cause resistance to these new compounds: the overproduction of chromosomally encoded beta-lactamases with predominating cephalosporinase activity, and the recently observed extended-spectrum beta lactamases. The overproduction of chromosomally mediated beta-lactamases has been observed only in some species (Enterobacter cloacae, Citrobacter freundii, Serratia spp.) which cause mainly nosocomial infections and are therefore of minor importance in outpatients. The extended-spectrum beta-lactamases TEM-3 to TEM-12 and SHV-2 to SHV-7 have been observed in various countries, they derived from the original enzymes by point mutations and occurred in intensive-care units. These enzymes may cause resistance to 3rd-generation cephalosporins including the recently developed orally active compounds. Moderate resistance to cefetamet is observed only in strains producing either the TEM-3 or the TEM-4 enzyme, whereas the prevalence of the other enzymes is of no consequence for the activity of cefetamet. Consequently, cefetamet will not exhibit a marked selection pressure favoring the spread of extended-spectrum beta-lactamase producing strains. PMID- 1516459 TI - Clinical studies in pediatric respiratory-tract infections: what is desirable, feasible, or simply misleading. AB - In recent years, attempts have been made to make the regulatory requirements for clinical studies more uniform, and much has been discussed on the issue of good clinical practice. There is no doubt that clinical trials involving new drugs have to be conducted according to the highest standards. However, ideal design is not always feasible or ethical. The ideal design for efficacy studies demands randomization, double-blind comparisons, adequate group size, specification of the type of patients and isolated organisms. The present paper points out some difficulties regarding these points when studying cephalosporins in pediatric respiratory-tract infections, and proposes some solutions. PMID- 1516460 TI - The pharmacokinetics of new oral cephalosporins in children. AB - Differences in the pharmacokinetic parameters of cephalosporins between children and adults may be predictable on the basis of the level of maturation of the physiologic processes involved in drug disposition. It appears that the most important of these factors (gastrointestinal, renal and hepatic function) are reasonably mature by the age of 1 year. As a result, the primary difference between adults and children relates to size and body composition. Comparable bioavailability is expected in children and adults. However, absolute values for systemic clearance (ClS) and volume of distribution (VSS) will be lower in children. It has been suggested that ClS in children is reduced in proportion to body surface area. This may also be true for the VSS of the cephalosporins since they distribute primarily into the extracellular fluid space which has been shown to be similar in children and adults when adjusted for surface area. If both ClS and VSS are proportional to surface area, half-life will be similar in adults and children. Data with cefetamet generally support these principles. Clearance normalized for body surface area averaged 69.3 ml/min/m2 in children aged 3-7 years, 64.9 ml/min/m2 in children of 8-12 years and 68.9 ml/min/m2 in adults. The VSS remained somewhat smaller in children than adults even after correction for surface area. Bioavailability and elimination half-life in children were similar to values in adults. Data with other new cephalosporins are limited, but differences between children and adults in bioavailability and half-life appear to be insignificant.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1516461 TI - Cefetamet pivoxil in pediatric otitis media. AB - Cefetamet, an oral 3rd-generation cephalosporin, was investigated in 40 children with acute otitis media in a comparative randomized trial. The efficacy of 20 mg/kg cefetamet syrup in 20 patients was compared with that of 20 mg/kg cefaclor in another 20, both drugs being given orally twice daily for 7 days. Tympanocentesis was performed for every child before the initiation of antimicrobial treatment. After 7 days treatment with cefetamet pivoxil, clinical cure was obtained in 12 patients, 3 were failures and 5 could not be assessed. In the cefaclor group, 10 patients were cured, 1 improved and 9 were failures. No severe adverse events were observed with either drug. PMID- 1516462 TI - Clinical trials on pediatric lower-respiratory-tract infection: results and comments with cefetamet pivoxil. AB - A total of 30 pediatric patients suffering from lower-respiratory-tract infections were admitted to a three-arm, open, randomized study comparing two different doses of cefetamet pivoxil (either 10 or 20 mg/kg b.i.d.; groups A and B, respectively) with the standard cefaclor treatment (10 mg/kg t.i.d.; group C) for 7-12 days. The 30 cases were randomly assigned to the three treatment arms which were comparable with regard to demographics as well as to diagnosis on admission and concomitant medication. The children ranged from 1.08 to 12 years in age, and comprised 18 males and 12 females, with a weight range of 11-42 kg. As is to be expected in these patients, bacteriology was mostly not assessable. The overall clinical outcome was cure in 9, 8 and 9 cases, respectively, and improvement in 1, 2 and 0 cases, respectively. In the cefaclor group 1 patient failed to respond. Signs and symptoms of disease improved significantly in the three treatment groups; there were no intergroup differences. Vital signs (morning and evening temperature and pulse rate) improved in parallel. Radiological results had improved by the end of treatment in 9/10 patients in group A, in 10/10 patients in group B, and in 9/10 evaluable patients in group C. Mild to moderate nausea or vomiting were each reported in 1 patient in group A. Platelet increase was reported as a mild adverse event in 2 patients in each of the cefetamet pivoxil groups and in 4 patients given cefaclor.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1516463 TI - Comparative study of cefetamet pivoxil and penicillin V in the treatment of group A beta-hemolytic streptococcal pharyngitis. AB - The efficacy of cefetamet pivoxil (20 mg/kg and 10 mg/kg b.i.d.) was investigated in an open, prospective, randomized, comparative multicenter trial involving 148 children suffering from group A beta-hemolytic streptococcal (GABHS) pharyngo tonsillitis. Phenoxymethylpenicillin given for 10 days was used as the reference drug and resulted in 15% treatment failures. After treatment with cefetamet pivoxil 20 mg/kg b.i.d., 2 failures (5.8%) were observed in 34 patients treated for 7 days and 2 (6%) in 33 patients after 10 days treatment. In 8 children treated with cefetamet pivoxil 10 mg/kg b.i.d. for 10 days, 7 were cured and 1 relapsed in the late follow-up. Recruitment for this dosage group is being continued. No serious adverse events occurred. Cefetamet pivoxil, given b.i.d., can be considered an alternative to phenoxymethylpenicillin in the treatment of GABHS pharyngo-tonsillitis. PMID- 1516464 TI - Myogenesis in the mouse. AB - The first striated muscle to form during mouse embryogenesis is the heart followed by skeletal muscle which is derived from the somites. The expression of genes encoding muscle structural proteins and myogenic regulatory sequences of the MyoD1 family has been examined using 35S-labelled riboprobes. In the cardiac tube, actin and myosin genes are expressed together from an early stage, whereas in the myotome, the earliest skeletal muscle, they are activated asynchronously over days. They are not expressed in the somite prior to myotome formation. One potential muscle marker, carbonic anhydrase III, is expressed in early mesoderm and subsequently in the notochord, similarly to the Brachyury gene. The myogenic sequences are not detectable in the heart. In the myotome they show distinct patterns of expression; this is discussed in the context of their role as muscle transcription factors. myf-5 is the only myogenic factor sequence present in the somite prior to muscle formation and thus is potentially involved in an earlier step of muscle determination. It is also present in the early limb bud, but the status of myogenic precursor cells in the limb in this context is less clear. PMID- 1516465 TI - Development of the skeletal system. AB - The analysis of the development of the skeletal system has been greatly facilitated by the availability of a large number of mouse mutants with skeletal defects. Whereas for many of these mutants a description of the main phenotypic abnormalities is known, molecular insight into the ontogeny of the skeletal system is limited. One of the few skeletal mutants for which the molecular basis is known is undulated. These mice have a defect in the differentiation of the sclerotome and Pax-1, a mouse paired-box containing gene, has been identified as a candidate gene for this mutation. A molecular analysis of three independent undulated alleles revealed that in each case the Pax-1 gene is affected. One of the alleles could be classified as a null allele, in which the Pax-1 gene is deleted. A phenotypic analysis shows that Pax-1 is required for proper differentiation of intervertebral discs and vertebral bodies. PMID- 1516466 TI - Development of the left-right axis. AB - Left-right is not an axis in the conventional sense but rather two mirror-image proximodistal axes, upon which a quantal piece of positional information (leftness or rightness) is superimposed for laterally asymmetric organ development. We are attempting to establish the stages at which left-right is specified and determined, but this is complicated by the apparent loss of normal handed development in embryos that are cultured from pre-neural plate stages. Experiments suggest that left-right is determined by the first somite stage. The loss of normal left-right development in early cultures is probably not due to removal of some maternal signal, even though embryos do develop in vivo with their axes in a specific orientation relative to the uterus. The fact that there are two random embryonic axis orientations, 180 degrees opposed to one another, and that the axes of the two uterine horns are mirror-images of each other make it unlikely that the uterus could impart a sense of left-right to the embryo. The right ovary produces more eggs than the left one; this is reversed in iv/iv situs inversus mice. Analysis of iv/iv mice shows a correlation of left-right abnormalities with sex and close relationships between the abnormal left-right development of some organs, for example the heart and spleen, that have no obvious developmental connection. PMID- 1516467 TI - The role of Sry in mammalian sex determination. AB - The testis-determining gene is the Y-linked gene responsible for initiating the developmental pathway leading to testis formation in males. A strategy based on determining the precise chromosomal location of this locus has been used to clone a new gene which has been called SRY in humans (Sry in mice). A variety of studies now show that this is indeed the testis-determining gene. Sry has a spatial and temporal pattern of expression which correlates with the initiation of testis differentiation. The amino acid sequence encoded by the gene suggests that the protein may function as a transcription factor, which fits well with models of sex determination. Some cases of XY sex reversal in humans and mouse have been attributed to mutations in SRY/Sry, indicating that it is normally necessary for testis determination. The finding that a genomic fragment carrying Sry can cause male development in XX mice has proved that Sry is the only gene from the Y chromosome necessary for testis determination. PMID- 1516468 TI - Epithelial-mesenchymal interactions in murine organogenesis. AB - Reciprocal, sequential interactions between embryonic epithelial and their mesenchymal stroma guide the cytodifferentiation and organization of both components. These morphogenetic interactions and their consequences are examined in two model systems in vitro: the mouse metanephric blastema and the tooth rudiment. Experimental approaches include dissection and recombination of the interacting tissues, localization of molecular changes by immunohistology and in situ hybridization. An early response of the mesenchyme is increased proliferation of cells in the vicinity of the epithelial inductor and their subsequent aggregation (condensation). In the kidney model disruption of this aggregation or prevention of assembly of the programmed cells results in impaired cytodifferentiation. If the cells are allowed to reaggregate, a phenotype is expressed not unlike that seen in normal in vivo conditions. Our present interest is focused on the early metabolic events associated with the condensation phenomenon. The cell surface proteoglycan syndecan and the matrix glycoprotein tenascin are expressed in the condensed mesenchyme and may mediate cell-matrix interactions. The expression patterns of certain growth factors suggest functions in signal transduction. PMID- 1516469 TI - The Wnt family of cell signalling molecules in postimplantation development of the mouse. AB - The mammalian Wnt gene family consists of at least ten members, all of which share a common structure. The N-terminus encodes a putative signal peptide sequence, suggesting that Wnt proteins are secreted. A number of absolutely conserved cysteine residues imply that inter- or intramolecular disulphide bonding is important to Wnt protein function. Wnt RNAs are localized to discrete regions of the postimplantation embryo and fetus, particularly within the developing central nervous system. Studies on Wnt gene expression strongly suggest that Wnt-mediated signalling is likely to be an important aspect of mouse development. One member of the family, Wnt-1, has been studied in some detail. By generating mutant alleles, we have demonstrated that Wnt-1 regulates regional development of the central nervous system at early somite stages. There is circumstantial evidence that some aspects of the pathway through which Wnt-1 action is mediated may be evolutionarily conserved. We propose that the Wnt family plays a major role in cell-cell interactions in the mouse. PMID- 1516470 TI - The TGF-beta-related DVR gene family in mammalian development. AB - The genes that encode the bone morphogenetic proteins and the Vg-related proteins are mammalian members of a group of TGF-beta-related genes, designated the DVR family, that includes the decapentaplegic gene of Drosophila and the Vg1 gene of Xenopus. Members of the DVR (decapentaplegic-Vg-related) family have been implicated in diverse processes during development, particularly in epithelial mesenchymal interactions. The results of our in situ hybridization studies with postimplantation mouse embryos provide evidence for the involvement of DVR family members, particularly DVR-2, DVR-4 and DVR-6, in specific inductive interactions during the development of many organs, including the limb, the whisker follicle and the heart. PMID- 1516471 TI - Use of embryonic stem cells to study mutations affecting postimplantation development in the mouse. AB - The generation and analysis of insertional mutations that perturb early postimplantation development provide a means to identify genes required at this stage of embryogenesis. We have been studying two independently generated insertional mutations termed 413.d and H beta 58 that result in early postimplantation lethality. Each mutation is associated with a distinct phenotype. 413.d mutant embryos become profoundly abnormal around the time of gastrulation: no identifiable embryonic axis or mesodermal structures are formed. H beta 58 mutant embryos proceed further in development, forming a relatively normal anteroposterior axis before developmental arrest occurs. We isolated embryonic stem cell lines homozygous for each of these mutations and assessed their differentiation abilities and developmental potential in vitro and after their introduction into wild-type blastocysts. From these studies we conclude that the 413.d mutation acts in a non-cell-autonomous fashion: mutant cells appear capable of participating, in conjunction with wild-type cells, in the formation of derivatives of all three primary cell lineages of the embryo. H beta 58 mutant embryonic stem cells are clearly pluripotent but they appear to be more restricted in their developmental potential, suggesting that the H beta 58 gene product may be required by specific tissues of the embryo. PMID- 1516472 TI - Genetic manipulation of the mouse via gene targeting in embryonic stem cells. AB - Gene targeting applied to totipotent embryonic stem (ES) cells is a very powerful means of creating highly specific mutations of genes in the mouse. The successful application of this technology is however constrained by both the types of mutations that can be generated at a target locus and the ability to reconstruct a germline chimera from the manipulated cells. We have developed two cell lines that can be routinely transmitted through the germline of chimeras after cloning and prolonged selection in tissue culture. We have also established a variety of methods for generating non-selected mutations at the X-linked hprt locus in ES cells. Our observations at this locus have enabled us to generate successfully a subtle mutation at the non-selectable Hox-2.6 locus. PMID- 1516473 TI - Establishment and organization of germ layers in the gastrulating mouse embryo. AB - By following the distribution of wheat germ agglutinin-gold-labelled cells in primitive streak stage embryos, we obtained direct evidence for a continuous recruitment of the embryonic ectoderm cells to the definitive endoderm and to the embryonic and extraembryonic mesoderm during gastrulation. The majority of the definitive endodermal cells ingressed through the anterior end of the primitive streak and were incorporated initially into the midline endoderm at the archenteron, but a small population of endodermal cells may be recruited by direct delamination from the embryonic ectoderm. The pre-existing visceral embryonic endoderm was progressively replaced, but not totally, by the newly recruited population which colonized the embryonic foregut and the notochord. The developmental fate of the recruited endoderm and that of cells in the embryonic ectoderm and the mesoderm of late primitive streak stage embryos indicate that concomitant with the establishment of the germ layers, an orderly allocation of prospective fetal tissues to specific parts of the body occurs simultaneously in all three germ layers. PMID- 1516474 TI - The gene trap approach in embryonic stem cells: the potential for genetic screens in mice. AB - The gene trap approach in embryonic stem cells was developed as a means to screen for genes expressed during early postimplantation development in the mouse. We have validated the approach by showing that lacZ from the integrated vector is activated by splicing to endogenous exons and expressed in embryos in patterns that mimic those of the endogenous genes. These insertions can produce developmental defects in homozygous mice. The results indicate that a large screen of gene trap cell lines on the basis of embryonic lacZ expression is feasible and should provide a new source of genes, mouse mutants and mouse strains that express lacZ in particular domains and lineages. The gene trap approach could be extended to a smaller screen for genes based on mutant phenotypes. PMID- 1516475 TI - Clonal analysis of cell fate during gastrulation and early neurulation in the mouse. AB - The foundation of the germ layers and the extraembryonic mesoderm from the epiblast between 6.5 and 7.5 days post coitum (p.c.) is accompanied by substantial cell proliferation. It is followed during the next 24 hours by the organization of major systems of the embryo such as the central nervous system, somites, heart and vascular system. Injection in situ of a short-term lineage label (horse radish peroxidase) into single epiblast cells at 6.7 days p.c. and analysis of the descendant clones in cultured embryos have been used to trace these processes and led to the following conclusions: (1) There is extensive but not indiscriminate cell mixing at the onset of gastrulation; epiblast cells spread towards the primitive streak and descendants are there progressively incorporated into mesoderm. (2) The fate map of the mouse epiblast at the early primitive streak stage is topologically similar to those of other vertebrates. (3) Germ layers and the extraembryonic mesoderm are not clonally distinct before gastrulation, the region of overlapping boundaries in the fate map being occupied by cells that will have descendants in more than one layer. (4) Cranial neurectoderm is mainly derived from axial epiblast immediately anterior to the primitive streak of the early streak stage embryo, clonal descendants being spread rostrocaudally in the developing neural tube. Contribution to the putative floor plate is made by progenitors some of which also contribute to notochord and mesoderm. PMID- 1516477 TI - Action of the Brachyury gene in mouse embryogenesis. AB - The murine developmental mutation T identifies a gene required in mesoderm formation. T/T mutant embryos develop normally to the primitive streak stage; during early organogenesis they show insufficient mesoderm and absence of the notochord. The mutants die at around 10 days of gestation because of the lack of the allantois. We have localized the T mutation relative to DNA markers and used a combination of genetic and molecular techniques to clone the T gene. Expression of the T gene is restricted to nascent mesoderm and to the notochord, the tissues most strongly affected by the mutation. Recent results suggest that the T gene encodes a nuclear factor involved in establishing notochord cell identity and differentiation, and is directly or indirectly involved in the organization of axial development. PMID- 1516476 TI - Use of chimeras to study gene function in mesodermal tissues during gastrulation and early organogenesis. AB - The origin of different mesodermal tissues during gastrulation and the developmental lability of mesodermal precursors can be mapped by transplanting marked epiblast cells to the same or a different position in a host egg cylinder, and assessing the subsequent fate of transplanted tissue. This information provides the context for assessing the role of particular patterns of gene expression during mesoderm formation and differentiation. For example, the stability of Hox gene expression can be examined by transplanting transgenically marked somites that express a particular Hox gene to a position in the somite file where it is not normally expressed. Such experiments can reveal not only the cues required for Hox gene expression but also the relevance of a circumscribed pattern of Hox gene expression to a specific developmental fate. A different approach to resolving gene function is to mix mutant cells known to affect mesoderm formation with normal cells and to determine the cell autonomy of mutant cells in a normal environment. Homozygous Brachyury (T/T) embryonic stem cell lines have been isolated and injected into normal blastocysts. The presence of T/T cells in chimeras results in mesodermal defects similar to those seen in the intact mutant. PMID- 1516478 TI - Accurate estimation of glomerular filtration rate in diabetic nephropathy from age, body weight, and serum creatinine. AB - OBJECTIVE: To assess, in diabetic nephropathy, the accuracy of a method that estimates glomerular function with age, body weight, and serum creatinine as parameters. RESEARCH DESIGN AND METHODS: Glomerular filtration rate (GFR) was measured 57 times in 20 subjects with insulin-dependent diabetes mellitus and nephropathy with a single injection of 51Cr-EDTA. At the same time, the estimated creatinine clearance (ml/min) was calculated with the Cockroft-Gault formula (140 - age [yr]) x body wt [kg] x K/serum creatinine [mumol/L]) K = 1.23 for men, 1.05 for women These values were then corrected for body surface area (1.73 m2). RESULTS: For GFR measurements less than 100 ml.min-1.1.73 m-2 (n = 41), there was a strong positive correlation with the estimated creatinine clearance corrected for body surface area (r = 0.94, P less than 0.0001). The slope of this regression line did not differ significantly from identity or the y-intercept from zero. On average, the Cockroft-Gault formula (corrected for body surface area) underestimated the GFR by only 3.1 ml.min-1.1.73 m-2 (9.7 SD). CONCLUSIONS: This formula, corrected for body surface area, gives accurate estimates of GFR when GFR less than 100 ml.min-1.1.73 m-2. This formula could be used with an acceptable degree of confidence when repeated isotope assessments of renal function in diabetic nephropathy are impracticable. PMID- 1516479 TI - Early sonographic evaluation for fetal growth delay and congenital malformations in pregnancies complicated by insulin-requiring diabetes. National Institute of Child Health and Human Development Diabetes in Early Pregnancy Study. AB - OBJECTIVE: It has been reported that early fetal growth retardation may be a useful marker for congenital malformations in diabetic pregnancies. To test this hypothesis, diabetic and nondiabetic women were sonographically evaluated during the first trimester. RESEARCH DESIGN AND METHODS: Fetal crown-rump lengths were measured sonographically at least once during the first 15 wk of pregnancy in 329 nondiabetic and 312 diabetic women. Of these, 289 nondiabetic and 269 diabetic women had sonograms before 10 wk of gestation and 283 nondiabetic and 269 diabetic women had sonograms between 10 and 15 wk of gestation. Early fetal growth delay was defined as a sonographic gestational age of greater than or equal to 6 days less than menstrual gestational age. RESULTS: The mean crown-rump lengths at 8 wk were 17.9 +/- 4.6 mm in the diabetic and 18.7 +/- 4.9 mm in the nondiabetic groups (P = 0.13). At 12 wk, the mean fetal crown-rump length was 58.5 +/- 8.8 mm for diabetic subjects and 60.6 +/- 8.7 mm for nondiabetic subjects (P = 0.04). Between 5 and 9 wk, 28 of 289 (9.7%) fetuses of nondiabetic subjects, 34 of 259 (13.1%) normal fetuses of diabetic subjects, and 2 of 10 (20%) malformed fetuses of diabetic subjects demonstrated growth delay (P = 0.31, normal vs. malformed diabetic). Between 10 and 15 wk of gestation, 28 of 283 (9.9%) fetuses of nondiabetic subjects, 32 of 256 (12.5%) normal fetuses of diabetic subjects, and 4 of 13 (30.8%) malformed fetuses of diabetic subjects demonstrated growth delay (P = 0.06, normal vs. malformed diabetic). Early fetal growth delay did not predict a reduced birth weight at term. CONCLUSIONS: Among insulin-dependent diabetic subjects who were moderately well controlled at conception, statistically significant but mild early fetal growth delay was present but did not appear to be useful clinically in predicting congenital malformations. Recommendations that growth delay demonstrated on early ultrasound be used as a predictor of congenital malformation require careful reexamination. PMID- 1516480 TI - Nonselective loss of contrast sensitivity in visual system testing in early type I diabetes. AB - OBJECTIVE: Psychophysical methods in patients with diabetes mellitus reveal deficits of central or foveal vision. Our aim was to evaluate the contrast sensitivity thresholds in 24 insulin-dependent (type I) diabetic patients with a short disease duration and without retinopathy, taking into account metabolic control. RESEARCH DESIGN AND METHODS: The control group consisted of age-matched nondiabetic subjects. None had visual or systemic symptoms. Contrast sensitivity measured at eight different spatial frequencies to sinusoidal bar patterns of 0.6 12.2 cycles/deg can detect functional defects in the spatially sensitive retinal ganglion cells or in higher visual pathways. We performed two different temporal types of contrast-sensitivity testing, dynamic (8 Hz) and static (0 Hz). RESULTS: Significant losses with dynamic contrast-sensitivity test at all but the highest spatial frequencies (i.e., 12.2 cycles/deg) were shown, whereas there was significant attenuation of contrast sensitivity at five spatial frequencies (1.0, 1.4, 2.2, 7.1, and 9.6 cycles/deg) in the static mode. Grating losses (less than 2SD of control means) of contrast sensitivity were found in 33.3% (dynamic) and in 72.9% (static) of eyes of diabetic patients. HbA1c values were positively correlated at variable spatial frequencies (1.0, 1.4, and 2.2 cycles/deg for dynamic test and 0.6, 1.0, 1.4, 2.2, 4.8, and 7.1 cycles/deg for static test). CONCLUSIONS: Our results suggest an early, generally nonselective neuronal damage of visual pathways that occurs before the onset of clinically detectable retinopathy. The visual deficit may be related directly to the effects of diabetes; repetitive minor hypoglycemic insults may contribute more than a marked hyperglycemic condition to the mechanisms underlying physiological changes along the optic nerve. PMID- 1516481 TI - Early infant diet and risk of IDDM in blacks and whites. A matched case-control study. AB - OBJECTIVE: To investigate the role of early infant feeding in the development of insulin-dependent diabetes mellitus (IDDM) and to determine whether an association exists in both blacks and whites. RESEARCH DESIGN AND METHODS: Black and white diabetic subjects were recruited from the Allegheny County and Children's Hospital of Pittsburgh IDDM Registries. Extensive infant diet histories were obtained from the diabetic subjects and their nondiabetic siblings, who were used as nondiabetic control subjects. Each diabetic subject was matched outside his/her family to an unrelated nondiabetic control subject on birth order, birth year (+/- 2 yr), and race, which resulted in 211 case-control pairs with a mean birth year of 1967. RESULTS: In whites, diabetic subjects were less likely to have been breast-fed than control subjects (odds ratio [OR] 0.5, 95% confidence interval [CI] 0.3, 0.9). Breast-feeding prevalence did not differ between black diabetic subjects and control subjects. Duration of overall and exclusive breast-feeding did not differ between diabetic and control subjects in the black and white cohorts. The following analyses, which examined whether the timing of the first breast milk substitute to which the infant was exposed differed between diabetic and control subjects, were conducted for exposure to any breast milk substitute and to breast milk substitutes that were cow's milk based. In whites, age at exposure to any breast milk substitutes and cow's milk based substitutes were similar between diabetic and control subjects. In blacks, the first exposure to breast milk substitutes occurred significantly earlier for any substitute (5.1 vs. 11.9 wk, P = 0.02) and marginally earlier for cow's milk based substitutes (3.9 vs. 8.5 wk, P = 0.07) in diabetic subjects compared with control subjects. The first exposure to breast milk substitutes was more likely to occur by 3 mo of age in black diabetic subjects compared with black control subjects (OR 3.3, 95% CI 1.1-10.0) after adjusting for maternal age at birth. The addition of breast-feeding status to the model only slightly weakened this association in blacks. CONCLUSIONS: The analyses of this study cohort suggest that the observed protective effect of breast-feeding on the risk of IDDM may be related to differences in the age at exposure to breast milk substitutes in blacks but not in whites. PMID- 1516482 TI - Elevated proinsulin levels related to islet cell antibodies in first-degree relatives of IDDM patients. AB - OBJECTIVE: To assess whether proinsulin levels are elevated in first-degree relatives of insulin-dependent diabetes mellitus (IDDM) patients and whether there is a relationship between proinsulin levels and the occurrence of immunological markers. RESEARCH DESIGN AND METHODS: Fasting proinsulin concentrations were measured in 85 first-degree relatives (54 siblings, 20 parents, 11 children) of IDDM patients and in 90 age- and weight-matched control subjects with no family history of diabetes mellitus. RESULTS: Fasting proinsulin levels (median, 25th, and 75th percentiles) were 8 pM (range 3.2-14 pM) in first degree relatives and 1.7 pM (range 1.7-4 pM) in control subjects (P less than 0.0001). Proinsulin was significantly elevated in siblings (7.2 pM, range 3.8-15 pM; P less than 0.0001), parents (9.8 pM, range 6.4-13 pM; P less than 0.0001), and children (6.6 pM, range 1.8-12 pM, P = 0.04) compared with control subjects but without differences between these groups. Islet cell antibody positive (ICA+) IDDM relatives had significantly higher proinsulin levels than ICA- (16 pM; range 7.2-25 vs. 6.9 pM, range 3.1-12 pM; P = 0.02). There was no difference between individuals with and without insulin autoantibodies. No difference in proinsulin levels was observed if the relatives were subdivided according to HLA-DR sharing with the diabetic proband. CONCLUSIONS: Fasting proinsulin concentrations were raised not only in siblings but also in parents and children of IDDM patients. Because proinsulin is more elevated in ICA+ than in ICA- subjects, increased proinsulin levels could reflect minor beta-cell damage due to previous immunological attack. PMID- 1516483 TI - Does glycemic control of type II diabetes suffice to control diabetic dyslipidemia? A community perspective. AB - OBJECTIVE: To assess the extent to which glycemic control by itself results in satisfactory control of diabetic dyslipidemia. RESEARCH DESIGN AND METHODS: A population-based case series consisting of 386 Mexican Americans and 94 non Hispanic whites with non-insulin-dependent (type II) diabetes was studied. All subjects answered questions about their medical history and care received and underwent a standardized oral glucose tolerance test and measurements of fasting serum lipid and lipoprotein concentrations. Three definitions of dyslipidemia were used: total cholesterol greater than 6.20 mM (240 mg/dl), triglyceride greater than 2.82 mM (250 mg/dl), and high-density lipoprotein cholesterol less than 0.90 mM (35 mg/dl). RESULTS: Despite having removed subjects receiving lipid lowering drugs, diabetic subjects who had been previously diagnosed and were under medical care exhibited a lower prevalence of hypertriglyceridemia than those who were newly diagnosed at the time of their survey visit, suggesting that conventional management was associated with a reduced frequency of this dyslipidemia. Among previously diagnosed cases, the prevalence of dyslipidemia rose with worsening glycemic control but there was little association with type of therapy (diet only, oral agents, or insulin) or frequency of physician visits. In general, the prevalence of dyslipidemia in diabetic subjects remained higher than in nondiabetic subjects, despite hypoglycemic therapy. CONCLUSIONS: The results suggest that glycemic control by itself does not suffice to control diabetic dyslipidemia and that significant numbers of diabetic subjects will need direct lipid management. Clinical trials are urgently needed to define the optimum management strategy for diabetic dyslipidemia. PMID- 1516484 TI - Glycosylated serum protein levels assayed with highly sensitive immunoradiometric assay accurately reflect glycemic control of diabetic patients. AB - OBJECTIVE: To develop a sensitive and reliable immunoreadiometric assay to measure glycosylated lysine residues on serum proteins (GSP) and to evaluate its efficacy in monitoring glycemic control. RESEARCH DESIGN: The effect of acute and chronic in vitro and in vivo changes in glucose levels on GSP concentration was evaluated. GSP determinations from insulin-dependent diabetic (IDDM) patients, non-insulin-dependent diabetic (NIDDM) patients, and control subjects were correlated with other indices of glycemic control. RESULTS: The GSP levels were unaffected by acute glucose changes after food or intravenous glucose administration but increased during storage at -20 degrees C due to in vitro glycosylation by endogenous glucose. Immediate acidification of the serum prevented this, permitting long-term storage despite high ambient glucose levels. In randomly selected diabetic patients, 96% of GSP values were greater than the mean +3SD of nondiabetic control subjects. In diabetic patients, GSP levels correlated with mean plasma glucose concentrations (Kendall correlation statistics 0.47, P less than 0.001), fasting plasma glucose levels (Kendall statistics 0.42, P less than 0.001), and glycosylated hemoglobin (GHb, Kendall statistics 0.30, P less than 0.005). Induction of near-normal glycemia in poorly controlled NIDDM patients reduced GSP levels with a slope consistent with a half time of disappearance of 4.7 +/- 0.4 days. GSP levels remained elevated in 6 of 10 well-controlled NIDDM patients, despite normal GHb concentrations. Chronic hypoglycemic states, like pregnancy and hyperinsulinemic hypoglycemia, were associated with significantly low GSP levels. CONCLUSION: We describe a reproducible and sensitive immunoradiometric assay for GSP that closely reflects the degree of glycemic control in diabetic patients. Further studies are needed to determine whether this assay may be useful in screening for glucose intolerance or gestational diabetes. PMID- 1516485 TI - In vivo demonstration of insulin-receptor defect with 123I-labeled insulin and scintigraphic scanning in severe insulin resistance. AB - OBJECTIVE: Insulin-receptor function in humans is usually studied in vitro on readily available cells, e.g., erythrocytes and fibroblasts. Although these cells are not metabolically important targets for insulin action, information derived from them are often taken as representative of other tissues. The aim of this study was to investigate insulin receptors in vitro on erythrocytes and in vivo on one of the main insulin-target organs, the liver. RESEARCH DESIGN AND METHODS: A 16-yr-old girl affected by severe insulin resistance was identified. Insulin receptor binding was measured on the erythrocytes of the patient and of 6 nondiabetic volunteers. The biodistribution of 123I-labeled insulin was studied in vivo by scintigraphic scanning in the insulin-resistant patient and in 10 nondiabetic volunteers. RESULTS: Erythrocytes of this patient displayed a markedly reduced [125I]insulin binding. In vivo 123I-insulin biodistribution was characterized by lack of hormone uptake by the liver (4 vs. 21% of the injected dose in control subjects) contrasting with intense accumulation of radioactivity in the kidneys. CONCLUSIONS: Our studies show that defects of insulin binding can be directly demonstrated in vivo on liver receptors with a noninvasive technique with low radiotoxicity. PMID- 1516486 TI - Hypertriglyceridemia in different degrees of glucose intolerance in a Finnish population-based study. AB - OBJECTIVE: To determine the prevalence of hypertriglyceridemia and the mean serum triglyceride concentrations in different degrees of glucose tolerance--non insulin-dependent diabetes mellitus (NIDDM), impaired glucose tolerance (IGT), and normal glucose tolerance (NGT). In addition, we analyzed the correlates of serum triglyceride concentration to explain why it is more prevalent in diabetic subjects. RESEARCH DESIGN AND METHODS: This study was a cross-sectional survey of 4000 people aged 45-64 yr randomly drawn from the population register of the Finnish population of the provinces of North Karelia and Kuopio in eastern Finland and Turku/Loimaa area in southwestern Finland and stratified by four 10 yr age- and sex groups. The final material comprised 96 subjects with NIDDM, 102 subjects with IGT, and 323 subjects with normal glucose tolerance classified on the basis of two 2-h oral glucose tolerance tests. The prevalence of hypertriglyceridemia by the glucose tolerance status and the variation in serum triglycerides associated with selected life-style and biochemical factors were executed as the main outcome measures. RESULTS: The prevalence of hypertriglyceridemia (greater than or equal to 2.3 mM) was 47.6% (95% confidence interval [CI] 32.5-62.7%) in NIDDM men, 21.9% (95% CI 7.6-36.2%) in IGT men, and 15.4% (95% CI 9.3-21.5%) in NGT. In women, hypertriglyceridemia was found in 51.9% (95% CI 38.6-65.2%) among those with NIDDM, 25.7% (95% CI 15.5-35.9%) among those with IGT, and 10.7% (95% CI 6.3-15.1%) in women with NGT. After adjusting for body mass index (BMI) and age, the difference in the prevalence of hypertriglyceridemia between the glucose tolerance groups remained significant in both men (P = 0.008) and women (P = 0.0001). High serum total cholesterol, high BMI, high waist-hip ratio, and low high-density lipoprotein (HDL) cholesterol were significantly associated with high serum triglycerides in all glucose tolerance groups. No synergistic effect between these parameters and glucose tolerance status was found. In multiple linear regression analyses, fasting plasma insulin, diabetes status, and serum uric acid were significant predictors of serum triglyceride concentration after taking into account age, BMI, and HDL and total cholesterol. The association between BMI and serum triglycerides in the regression analysis was significant only when plasma insulin was not included in the model. CONCLUSIONS: Hypertriglyceridemia is common in subjects with NIDDM and IGT and is often associated with low HDL cholesterol, high total cholesterol, hyperinsulinemia, and elevated serum uric acid concentration. PMID- 1516487 TI - Biosynthetic human proinsulin. Review of chemistry, in vitro and in vivo receptor binding, animal and human pharmacology studies, and clinical trial experience. AB - OBJECTIVE: To describe the rationale for the preclinical and clinical developmental course of human proinsulin (HPI), the second product after human insulin for the treatment of diabetes mellitus to be manufactured by DNA technology. RESEARCH DESIGN AND METHODS: The relevant and available published and unpublished preclinical and clinical information generated on pork proinsulin and human proinsulin has been integrated to demonstrate how certain clinically attractive features of pork proinsulin (a soluble intermediate-acting and possibly hepatospecific insulin agonist) led to the development of HPI. RESULTS: Clinical pharmacology studies demonstrated that HPI was definitely, although marginally, hepatospecific. More striking was the finding that the intrasubject/patient coefficient of variation of response to HPI was significantly less than that observed with NPH insulin. However, the fact that unique efficacy in controlled multicenter studies was not demonstrated suggested that these pharmacological features were not translated into clinical benefit. In one multicenter new patient study there were six myocardial infarctions, including two deaths, in patients treated for greater than or equal to 1 yr with HPI and none in the control group. CONCLUSIONS: To obtain an independent review of the risks and benefits of HPI, in February 1988, Lilly convened a consultant group that examined all relevant information on HPI available. These experts shared our concerns about the safety of HPI in light of the failure to demonstrate unique efficacy. Accordingly, clinical trials with HPI were suspended in February 1988. Experience with HPI demonstrates the challenge associated with the development of new drugs in general and insulin agonists in particular. PMID- 1516488 TI - Muscle blood flow in diabetes mellitus. Evidence of abnormality after exercise. AB - OBJECTIVE: To determine whether muscle blood flow before and after exercise is abnormal in patients with diabetes mellitus. RESEARCH DESIGN AND METHODS: Muscle blood flow (MBF) was measured with the 133Xe clearance technique in 15 nondiabetic subjects, 10 patients with insulin-dependent diabetes mellitus (IDDM), and 11 patients with non-insulin-dependent diabetes (NIDDM) at rest and after exercise. None of the patients had neuropathy. RESULTS: The median resting MBF was similar in all three groups. The median postexercise MBF was significantly greater in nondiabetic subjects (40.1 ml.min-1.100 g-1 of tissue) than in patients with IDDM (25.7 ml.min-1.100 g-1 of tissue; P less than 0.01) or NIDDM (14 ml.min-1.100 g-1 of tissue; P less than 0.01). The difference between IDDM and NIDDM was not significant. CONCLUSIONS: Diabetic patients have abnormalities of MBF in response to exercise. This abnormality occurs in the absence of clinical diabetic neuropathy. PMID- 1516489 TI - Maintenance of sulfonylurea responsiveness in NIDDM. Randomized double-blind study of intermittent glyburide therapy. AB - OBJECTIVE: To assess the effectiveness of intermittent administration of sulfonylurea (glyburide) to patients with non-insulin-dependent diabetes mellitus (NIDDM). RESEARCH DESIGN AND METHODS: A randomized, double-blind, prospective trial compared daily administration with intermittent administration of glyburide to patients who initially responded to the drug. Twenty-eight of 60 patients with NIDDM achieved the predetermined improvement in plasma glucose concentration on glyburide therapy. These 28 responders were enrolled into a 16-wk trial of daily versus intermittent (2 wk on, 2 wk off) glyburide treatment. Laboratory assessment of glycemic control and insulin secretion in fasting and 2-h postprandial states was done every 2 wk. RESULTS: Patients on continuous glyburide therapy maintained their glycemic control throughout the study. In contrast, patients on the intermittent schedule lost their glycemic control immediately after being placed on placebo. Despite a significant response to each sulfonylurea pulse, these subjects never regained their baseline glycemic levels. Their fructosamine and HbA1c concentrations deteriorated and remained significantly higher than those of the continuously treated subjects. CONCLUSIONS: Results suggest that administration of glyburide on an intermittent basis after a 2-wk drug-free period to patients initially rendered responsive to sulfonylurea therapy is without clinical merit. PMID- 1516490 TI - Evaluation of capillary collection system for HbA1c specimens. AB - OBJECTIVE: We evaluated the accuracy and stability of a capillary HbA1c collection system for use with a high-performance liquid chromatography analyzer. RESEARCH DESIGN AND METHODS: The collection system requires that 5 ul blood is drawn into a calibrated capillary tube, which is then placed into a vial of stabilizing solution and sent for analysis. The study was conducted on simultaneously drawn capillary and venous blood specimens from 47 pediatric diabetes patients. Accuracy was determined by comparing the capillary to the venous HbA1c values. Stability was measured by analyzing 17 capillary specimens over 3 wk. RESULTS: There was excellent agreement between the capillary and venous HbA1c values (capillary 0.959, venous +0.494, R2 = 98.7%). The capillary HbA1c values were 0.2% higher than the venous HbA1c values and decreased gradually over time (0.1% HbA1c/week) when stored at room temperature. CONCLUSIONS: The Bio-Rad (Richmond, CA) collection system is accurate, stable, and simple to use. PMID- 1516491 TI - Immunological and metabolic responses of patients with history of antibody induced beef insulin resistance to treatment with beef, pork, human, and sulfated beef insulin. AB - OBJECTIVE: We evaluated immunological and metabolic responses during therapy with beef (B), pork (P), human (H, rDNA), and sulfated beef (SB) insulins in patients with insulin-antibody-mediated insulin resistance. RESEARCH DESIGN AND METHODS: A randomized double-blind sequential crossover study was performed with each insulin administered for 56 days unless dose reached 200 U/day or allergy developed. Participants were 26 individuals with history of B-P insulin dosage greater than or equal to 200 U/day and insulin binding capacities greater than 0.216 nM (30 mU/ml serum). Twenty-one participants completed the study. Insulin dosage/day, fasting plasma glucose, percentage HbA1, insulin antibody binding capacity (IABC), bound insulin (BI), percentage binding of 125I-labeled B, P, and H insulins, and receptor inhibition factor (RIF) were assessed. RESULTS: Mean insulin dosage (U/day) was significantly greater on B (88.9) than on P (29.2), H (29.4), or SB (29.6). On B, dosage increased in 12 individuals and reached 200 U/day in 6 individuals. Mean fasting plasma glucose (12.1 mM) and HbA1 (11%) were significantly higher on B than on P, H, and SB. Mean IABC, bound insulin, RIF, and percentage of B, P, and H bound were significantly higher on B than on P, H, and SB. Prolonged treatment with SB before entry into the study (greater than 5 wk) resulted in a blunted anamnestic response to B insulin. CONCLUSIONS: Rechallenge with B results in anamnestic immunological response and deterioration of metabolic control. SB, H, and P insulins have equivalent effects in patients with insulin antibody-mediated immunologic resistance. PMID- 1516492 TI - Gestational diabetes. State of the union. PMID- 1516493 TI - Data transfer from biostator. Facilitation of analysis of glucose-clamp experiments. PMID- 1516494 TI - Reduction of hyperinsulinemia by glyburide--scientific fact or advertising fiction? PMID- 1516495 TI - Insulin resistance in malnutrition-related diabetes mellitus is not mediated by insulin antibodies. PMID- 1516496 TI - Hyperproinsulinemia in type II diabetes. PMID- 1516497 TI - Onset of NIDDM occurs at least 4-7 yr before clinical diagnosis. AB - OBJECTIVE: To investigate duration of the period between diabetes onset and its clinical diagnosis. RESEARCH DESIGN AND METHODS: Two population-based groups of white patients with non-insulin-dependent diabetes (NIDDM) in the United States and Australia were studied. Prevalence of retinopathy and duration of diabetes subsequent to clinical diagnosis were determined for all subjects. Weighted linear regression was used to examine the relationship between diabetes duration and prevalence of retinopathy. RESULTS: Prevalence of retinopathy at clinical diagnosis of diabetes was estimated to be 20.8% in the U.S. and 9.9% in Australia and increased linearly with longer duration of diabetes. By extrapolating this linear relationship to the time when retinopathy prevalence was estimated to be zero, onset of detectable retinopathy was calculated to have occurred approximately 4-7 yr before diagnosis of NIDDM. Because other data indicate that diabetes may be present for 5 yr before retinopathy becomes evident, onset of NIDDM may occur 9-12 yr before its clinical diagnosis. CONCLUSIONS: These findings suggest that undiagnosed NIDDM is not a benign condition. Clinically significant morbidity is present at diagnosis and for years before diagnosis. During this preclinical period, treatment is not being offered for diabetes or its specific complications, despite the fact that reduction in hyperglycemia, hypertension, and cardiovascular risk factors is believed to benefit patients. Imprecise dating of diabetes onset also obscures investigations of the etiology of NIDDM and studies of the nature and importance of risk factors for diabetes complications. PMID- 1516498 TI - Coronary heart disease incidence in NIDDM patients in the Helsinki Heart Study. AB - OBJECTIVE: To determine coronary heart disease (CHD) incidence among dyslipidemic subjects with non-insulin-dependent diabetes mellitus (NIDDM) and to assess the effect of lipid-modifying treatment on serum and lipoprotein lipids and the CHD incidence in these patients. RESEARCH DESIGN AND METHODS: Of the 4081 men participating in the Helsinki Heart Study, a coronary primary prevention trial with gemfibrozil in middle-aged men with high non-high-density lipoprotein (HDL) cholesterol (greater than 5.2 mM; 200 mg/dL), 135 had NIDDM at entry. The incidence of definite myocardial infarction and cardiac death and changes in serum and lipoprotein lipids were determined during the 5-yr trial in the NIDDM patients and compared with those observed in nondiabetic trial participants. RESULTS: Compared with nondiabetic subjects, NIDDM patients had lower HDL cholesterol (P less than 0.001), higher triglyceride concentration (P less than 0.0001), and greater body mass index (P less than 0.001), there were more hypertensive patients (P less than 0.001) among them. The incidence of myocardial infarction and cardiac death was significantly higher among diabetic than nondiabetic participants (7.4 vs. 3.3%, respectively, P less than 0.02). CHD incidence in the gemfibrozil-treated diabetic men (n = 59) was 3.4% compared with 10.5% in the placebo group (NS). In multivariate analysis, diabetes (P less than 0.05), age (P less than 0.0001), smoking (P less than 0.0001), low HDL cholesterol (P less than 0.05), and high low-density lipoprotein cholesterol (P less than 0.005) were independently related to CHD incidence. Gemfibrozil-induced serum and lipoprotein lipid changes in diabetic patients were similar to those observed in nondiabetic subjects. CONCLUSIONS: Compared with similarly dyslipidemic nondiabetic subjects, patients with NIDDM are at markedly increased risk of CHD. This elevated risk can be somewhat reduced by gemfibrozil. PMID- 1516499 TI - Effect of glycemic control on growth velocity in children with IDDM. AB - OBJECTIVE: To determine the effect of glycemic control on growth velocity in children with insulin-dependent diabetes mellitus. RESEARCH DESIGN AND METHODS: One hundred twenty-two children with insulin-dependent diabetes mellitus were studied over a 5-yr period. Every 4 mo, glycemic control was assessed by measuring total glycosylated hemoglobin (GHb), pubertal status was determined by physical examination, and height was measured with a stadiometer. Height measurements were normalized for age and sex by converting them to tau scores (the number of SD above or below the mean for age and sex). Alterations in growth velocity were determined by the change in tau scores (delta tau) between visits (i.e., no change in tau score = normal growth velocity; decrease in tau score = growth deceleration; and increase in tau score = growth acceleration). RESULTS: A linear relationship was seen between GHb levels and the change in tau scores (r = -0.117, P = 0.001). GHb values less than 8% were associated with growth acceleration (delta tau = +0.10 +/- 0.03), and the greatest growth deceleration occurred when GHb was greater than 16% (delta tau = -0.07 +/- 0.03). The level of GHb at which growth suppression occurred (mean delta tau became negative) was dependent on pubertal status: Tanner stage 1 greater than or equal to 10%, Tanner stages 2 and 3 greater than or equal to 8%, Tanner stages 4 and 5 greater than or equal to 16%. CONCLUSIONS: Linear growth velocity in children with insulin dependent diabetes mellitus is heavily related to metabolic control. Children who are prepubertal or in the early stages of puberty are the most vulnerable to growth suppression. Once puberty is well established, growth suppression does not occur until marked hyperglycemia (GHb greater than 16%) exists. PMID- 1516500 TI - Morning or bedtime NPH insulin combined with sulfonylurea in treatment of NIDDM. AB - OBJECTIVE: To compare the effect of morning and bedtime NPH insulin combined with daytime sulfonylurea on glycemic control in non-insulin-dependent diabetes mellitus (NIDDM) patients no longer responding to treatment with sulfonylureas alone. RESEARCH DESIGN AND METHODS: Twenty-four NIDDM patients who fulfilled these criteria were randomized to treatment with Protaphan human insulin in the morning or at bedtime (22 +/- 1 IU) plus 3.5 mg glibenclamide twice a day. RESULTS: Morning and bedtime NPH insulin resulted in equal reduction of HbA1 (from 13.5 +/- 0.3 to 9.4 +/- 0.1 and 9.6 +/- 0.2%, respectively) and mean self monitored blood glucose (9.2 +/- 0.5 vs. 10.1 +/- 0.4 mM). Bedtime insulin resulted in lower morning blood glucose (7.8 +/- 0.5 vs. 9.1 +/- 0.4 mM; P less than 0.01), whereas morning insulin resulted in lower evening blood glucose (10.1 +/- 0.6 vs 12.1 +/- 0.6 mM, P less than 0.01). CONCLUSIONS: Morning and bedtime NPH insulin combined with glibenclamide are equipotent in the treatment of NIDDM patients with secondary failure to sulfonylurea. However, this treatment regimen normalizes blood glucose only in a small group of patients. Therefore, more intensified insulin therapy seems to be required to achieve this goal. PMID- 1516501 TI - Intracellular free magnesium deficiency plays a key role in increased platelet reactivity in type II diabetes mellitus. AB - OBJECTIVE: Mg deficiency may be an important factor leading to cardiovascular disease. Diabetic subjects show an increase in platelet reactivity that can enhance the risks of vascular disease. In addition, diabetic patients have been reported to be at risk of developing extracellular Mg deficiency. However, the intracellular free Mg concentration and its role in the enhanced platelet reactivity in diabetes is not known. RESEARCH DESIGN AND METHODS: We evaluated the intracellular erythrocyte (RBC) Mg2+ concentration in 20 non-insulin dependent (type II) diabetics. In addition, the effects of intravenous 3-h drip or 8 wk of oral Mg supplementation on intracellular RBC Mg2+ levels and platelet reactivity was studied. To more clearly evaluate the direct role of Mg in these effects, we induced isolated Mg deficiency in 16 nondiabetic control subjects with an Mg-free liquid diet for 3 wk. RESULTS: The intracellular RBC Mg2+ concentration of diabetic patients was significantly reduced compared with values in nondiabetic control subjects (166 +/- 7 vs. 204 +/- 7 microM, P less than 0.01). Serum Mg levels were also reduced in the diabetic patients compared with the control subjects (1.59 +/- 0.04 vs. 1.9 +/- 0.1 mEq/L, P less than 0.05). Oral Mg supplementation for 8 wk (400 mg/day) restored RBC Mg2+ concentration to normal without significantly changing serum Mg concentration. Both intravenous and oral Mg supplementation markedly reduced platelet reactivity in response to the thromboxane A2 analog, U46619. The Mg-free diet resulted in a significant reduction in RBC Mg2+ concentration and markedly enhanced the sensitivity of platelet aggregation to U46619 and ADP. CONCLUSIONS: These results suggest that type II diabetic patients have intracellular Mg2+ deficiency and that Mg deficiency may be a key factor in leading to enhanced platelet reactivity in type II diabetes. Therefore, Mg supplementation may provide a new therapeutic approach to reducing vascular disease in patients with diabetes. PMID- 1516502 TI - Stress buffering and glycemic control. The role of coping styles. AB - OBJECTIVE: To test the hypotheses that chronic psychosocial stress is associated with worse glycemic control and that coping moderates (buffers) this effect. RESEARCH DESIGN AND METHODS: Subjects consisted of 105 insulin-treated adults from the Diabetes Division of Henry Ford Hospital who filled out questionnaires on stress and coping and received an HbA1 test at a clinic appointment. Six coping styles were examined, including both emotion- and problem-focused styles. Two standardized stress inventories were administered. Ineffective coping was defined as scoring below the median for stress-dampening coping styles and above the median for stress-exacerbating styles. RESULTS: Stress was significantly (P less than 0.05) correlated with higher HbA1 in all but one ineffective coping subgroup. Conversely, none of 12 correlations between stress and glycemic control was significant in the effective coping subgroups. CONCLUSIONS: Chronic psychosocial stress is associated with worse glycemic control among those who do not cope effectively with stress. Effective coping can protect individuals from the deleterious effects of stress. PMID- 1516503 TI - Sensory function at diagnosis and in early stages of NIDDM in patients detected through screening. AB - OBJECTIVE: We studied whether sensory function abnormalities are present at diagnosis and whether they develop in the early stages of non-insulin-dependent diabetes (NIDDM). RESEARCH DESIGN AND METHODS: Quantitative assessments of vibration sensitivity at the hallux and index fingers, and thermal sensitivity at the hallux were performed at screening (2-h oral glucose tolerance tests) for diabetes in 364 individuals. Twenty-five subjects diagnosed with NIDDM and 25 matched nondiabetic subjects were restudied after an interval of 12-41 mo. RESULTS: When those with NIDDM (n = 41) or impaired glucose tolerance (IGT) (n = 38) were compared with nondiabetic subjects, there were no significant differences in sensory function indices. However, the vibration threshold and HbA1c were related among those found to be hyperglycemic (IGT and NIDDM combined P less than 0.05; NIDDM alone P less than 0.05). Among diabetic subjects, the vibration threshold and interaction term of height and Hba1c were positively related in a multiple regression analysis (P less than 0.01). There were increments in all sensory thresholds in diabetic patients at follow-up (P less than 0.05 for all). Increments were smaller in control subjects. CONCLUSIONS: These data suggest that although sensory function tends to be normal at diagnosis in NIDDM patients, there appears to be a diminution in sensory function as the disease progresses. An interaction between metabolic factors and height may influence sensory function early in the course of NIDDM. PMID- 1516504 TI - Effect of thermal biofeedback-assisted relaxation training on blood circulation in the lower extremities of a population with diabetes. AB - OBJECTIVE: Investigate the effect of relaxation training/thermal biofeedback on blood circulation in the lower extremities of diabetic subjects. RESEARCH DESIGN AND METHODS: Diabetic subjects (n = 40) aged 17-73 yr were volunteers recruited through the University of Wisconsin-La Crosse, the local ADA Chapter, and a medical clinic. A within-subjects experimental design was used. During phase 1, all subjects used a self-selected relaxation method and recorded toe temperatures daily. During phase 2, subjects were taught a biofeedback-assisted relaxation technique designed to elicit sensations of warmth in the lower extremities and increase circulation and temperature. Subjects relaxed at home with the use of a designated relaxation tape. They measured and recorded toe temperatures. Each phase lasted 4 wk. RESULTS: Toe temperature and blood volume pulse (BVP) data were gathered at the beginning and end of phases 1 and 2. Paired t tests compared the means of temperature percent change scores between 1 and 2. Mean temperature change scores were 8.73% (phase 1) and 31.38% (phase 2) (t = -8.00, df = 39, P less than 0.001). Mean BVP change scores were 2.33% (phase 1) and 22.47% (phase 2) (t = -9.24, df = 35, P less than 0.001). Based on eta squared, 71% of the BVP increase in phase 2 was attributed to the relaxation technique. A multiple regression analysis indicated that none of the other examined variables affected by diabetes were significant predictors of BVP increase. CONCLUSIONS: Data indicate that diabetic patients show significant increases in peripheral blood circulation with this technique. This noninvasive method could serve as an adjunct treatment for limited blood flow in some complications of diabetes. PMID- 1516505 TI - Controversial beliefs about diabetes and its care. AB - OBJECTIVE: The purpose of this study was to identify specific beliefs that differentiate health-care professionals whose attitudes toward diabetes agreed most strongly with a group of national diabetes experts from those whose attitudes disagreed most strongly. RESEARCH DESIGN AND METHODS: The sample for this study included 271 physicians, 834 nurses, and 546 dietitians who completed a Diabetes Attitudes Survey. The sample included specialists in diabetes care and nonspecialists. Controversial beliefs about diabetes and its care were determined by comparing the beliefs of the 10% of the sample whose attitudes were most concordant (with the national panel) with the beliefs of the 10% of the sample whose attitudes were the most discordant. Ten beliefs met the criteria for being defined as controversial. RESULTS: The most controversial beliefs concerned whether the patient or the physician should be the primary decision maker in diabetes care, the meaning of patient noncompliance, and the seriousness of non insulin-dependent diabetes mellitus. The 10% of the sample with the most discordant attitudes contained a disproportionately large number of physicians, nonspecialists in diabetes, and health-care professionals who had been in practice longer than the other members of the sample. CONCLUSIONS: This study identifies some important differences in beliefs between younger health-care professionals who specialize in diabetes and older nonspecialists. Such beliefs should be addressed in continuing education programs with the aim being to foster the widespread adoption of a contemporary approach to diabetes care. PMID- 1516506 TI - Metabolic impact of education in NIDDM. AB - OBJECTIVE: To evaluate the impact of a model program of diabetes education and weight reduction on diabetes control and weight loss in obese individuals with non-insulin-dependent diabetes mellitus (NIDDM). RESEARCH DESIGN AND METHODS: Eighty-two obese diabetic subjects were randomized to three levels of educational intensity: 1) a single individual session, 2) a 12-wk behavior-oriented diabetes education and weight control group intervention, or 3) group intervention plus six individual follow-up sessions. Repeated measures of weight, fasting blood glucose, and HbA1c were collected. Measures of diabetes knowledge, skills, and attitudes were also obtained. RESULTS: By 6 mo, all three intervention groups had a significant weight loss (P less than 0.01). The mean weight loss of approximately 10 lb was independent of treatment group and was maintained over the duration of the study. However, significant improvement in metabolic control was associated with participation in the diabetes education-weight reduction intervention. CONCLUSIONS: The findings of this study indicate that a cognitive behavioral group intervention of diabetes knowledge and weight reduction training can produce weight loss and improvements in diabetes control. The addition of individual counseling as a follow-up maintenance strategy does not appear to have any advantage. PMID- 1516507 TI - Use of health maintenance organization data bases to study pharmacy resource usage in diabetes mellitus. AB - OBJECTIVE: To evaluate use of medications by patients with diabetes. RESEARCH DESIGN AND METHODS: We analyzed the computerized pharmacy data base of a large health maintenance organization to evaluate cost impact and patterns of usage for all pharmacy products by a defined population of diabetic patients. RESULTS: Diabetic patients received 31.2 dispenses/yr compared with 11.5 for control patients. Total pharmacy costs were threefold higher for diabetic patients ($621 vs. 207/yr) and accounted for approximately 17% of their total health-care costs. Products specifically for the care of diabetes averaged $175/yr or approximately 4.5% of their total health-care costs: 57% received an oral hypoglycemic agent, 34% received insulin, and 6% received both. Cardiovascular drugs accounted for 29% of total costs. There was increased use of most classes of medication by patients with diabetes. CONCLUSIONS: Health maintenance organization management data bases, particularly those storing pharmacy dispensing data, provide useful information on the impact of chronic disease. People with diabetes receive a greater number of most types of medication with a greater overall cost than do nondiabetic people. Previous studies have underestimated the contribution of pharmacy purchases to the costs of caring for a diabetic population. PMID- 1516508 TI - Clinical trial of programmable implantable insulin pump for type I diabetes. AB - OBJECTIVE: The first step in the evolution of an artificial pancreas is the development of a reliable implantable pump for insulin delivery. Despite recent advances, significant issues remain, including small size of studies and frequent irreversible catheter obstructions. We report safety, feasibility, and efficacy results from 56 patients, representing 73 patient-yr of pump experience, entered into a multicenter trial with a new implantable programmable pump. RESEARCH DESIGN AND METHODS: All patients had insulin-dependent (type 1) diabetes, were 38 +/- 8 yr old, and were not prone to severe hypoglycemia. The pump (Infusaid 1000) has a pulsatile mechanism powered by freon-vapor pressure. Its rate is regulated by battery-powered valves, operated via a hand-held programmer. The pump is refilled transcutaneously with 25 ml U100 insulin (Hoechst 21PH) on a monthly basis and has a second septum (side port) proximal to the catheter, which allows flushing the catheter or lavaging the pump unit. The pumps were implanted after 3 mo intensive subcutaneous insulin therapy and catheters were positioned either in the peritoneum (i.p., n = 38) or the superior vena cava (i.v., n = 18). RESULTS: All implanted pumps have functioned safely with no instance of overdelivery or stoppage. The most frequent complications were flow slow downs, presumably due to insulin precipitation within the pump, which occurred in 86% of pumps and were resolved in all but one case by lavaging the pump in situ with alkaline solution. Flow slow downs due to catheter obstruction occurred in 52% of the intravenous catheters but only 21% of the intraperitoneal catheters (P less than 0.05) and were resolved in all but two cases by diluent flushing through the sideport. Incidence of severe hypoglycemia decreased from 0.47 before implant to 0.05 episodes/patient-yr after pump implantation (P less than 0.001). Mean HbA1c fell from 7.4 +/- 1.2% after intensive subcutaneous therapy to 7.1 +/- 1.0% 12 mo after implantation. Only 2 patients withdrew from study after recurrent catheter problems, and quality-of-life questionnaires showed improvement in satisfaction with diabetes-specific quality of life when on implantable pump therapy. CONCLUSIONS: Insulin therapy with implantable pumps is effective and safe for periods up to 1.7 yr with a decreased risk of severe hypoglycemia than with intensive subcutaneous insulin therapy. PMID- 1516509 TI - Lipid and lipoprotein levels in patients with IDDM diabetes control and complication. Trial experience. The DCCT Research Group. AB - OBJECTIVES: To compare lipid and lipoprotein levels in patients with insulin dependent diabetes mellitus (IDDM) with values in similarly aged nondiabetic subjects and analyze the effects of demographic variables, metabolic control, and other factors on the lipid and lipoprotein levels in the diabetic population. RESEARCH DESIGN AND METHODS: Fasting total cholesterol, triglyceride, low-density lipoprotein (LDL) cholesterol, and high-density lipoprotein (HDL) cholesterol levels measured during screening for the Diabetes Control and Complications Trial (DCCT) in 1569 generally healthy IDDM patients, between the ages of 13 and 40 yr and with 1-15 yr diabetes duration, were compared with values obtained with similar methods in the Lipid Research Clinics (LRC) prevalence study of nondiabetic individuals. RESULTS: When similarly aged groups of IDDM and nondiabetic subjects were compared, higher total and LDL cholesterol and lower HDL cholesterol lipid profiles were restricted to younger (13-24 yr) female diabetic subjects. In general, IDDM males and older IDDM females had similar or slightly less atherogenic profiles than similarly aged nondiabetic subjects. Metabolic control, measured by HbA1c, and body weight (% of ideal body wt) correlated positively with total cholesterol, LDL cholesterol, and triglyceride levels. CONCLUSIONS: Lipid and lipoprotein levels in the generally healthy IDDM volunteers for the DCCT are similar to those in the nondiabetic population. More atherogenic profiles were present only in younger IDDM women compared with nondiabetic women. The differences between the DCCT data and older studies that demonstrated more profound abnormalities in lipid levels in IDDM populations may reflect patient selection and/or changes in dietary patterns (higher-carbohydrate and lower-fat content) and in glucose control that has occurred in recent years. PMID- 1516510 TI - Temporal variation in incidence of IDDM in Canterbury, New Zealand. AB - OBJECTIVES: To establish the statistical significance of observed variations over the last decade in the incidence of insulin-dependent diabetes mellitus (IDDM) in the 0- to 19-yr-old age-group and to determine whether incidence has increased in Canterbury, New Zealand. RESEARCH DESIGN AND METHODS: The Canterbury, New Zealand, Diabetes Registry has recorded all incidence cases of diabetes mellitus prospectively since 1982. All IDDM subjects aged 0-19 yr at diagnosis and using insulin are included in the study. Ascertainment is believed to be 100%. Prevalence was recorded at 1 January 1982 and 1 January 1990. Annual incidence for 1982-1990 was determined using age and sex cross-sectional census population denominators. The statistical significance of temporal, age, sex, and seasonal variations in incidence rates was ascertained by Poisson regression models (GLIM statistical software). RESULTS: Prevalence on 1 January 1990 was 115/100,000. Incidence rates during the 9 yr were periodic, with two major peaks--one in the early 1980s, the other in 1989 continuing into 1990. The temporal variation (P less than 0.02) was not age or sex specific. Incidence rates for boys were three- to fourfold higher during peak versus trough years, with a peak level of 20.7/100,000 in 1990. For girls, there was less variation, with a peak rate of 21.6/100,000 in 1990. There has been no significant increase in IDDM incidence over time. The mean rate of incidence across all age-groups for 1982-1990 was 12.7/100,000 person-yr. A significant seasonal association to the onset of IDDM was found only in boys, with incidence rates being significantly higher in winter than in summer (P less than 0.01). CONCLUSIONS: IDDM in Canterbury, New Zealand, presents in cycles of incidence peaks and troughs, each spanning 2-3 yr. PMID- 1516511 TI - Xerostomia in diabetes mellitus. AB - OBJECTIVE: To determine the prevalence of xerostomia in a group of ambulatory diabetic patients and to compare the following in patients with and without xerostomia: 1) flow rates of saliva and lacrimal fluid, 2) the presence of other symptoms suggestive of oral and extraoral dryness, 3) indexes of glycemic control, and 4) noninvasive measures of cardiovagal autonomic nervous system function. RESEARCH DESIGN AND METHODS: Forty adult diabetic patients and an equal number of age- and sex-matched healthy nondiabetic control subjects were studied. Subjects who consumed xerogenic drugs or had other significant diseases were excluded from the study. A questionnaire was administered to all patients, and the following tests were performed: resting and stimulated flow rates on whole saliva; Schirmer's test (lacrimal fluid), serum glucose and HbA1, expiration inspiration ratio, 30:15 ratio, Valsalva ratio, and the systolic blood pressure response to standing. RESULTS: Forty-three percent of diabetic patients complained of xerostomia, of which 82% were women. The oral dryness was not related to age or the type and duration of diabetes. Symptoms of water loss and oropharyngeal, ocular, and vaginal dryness were much more common in the xerostomic than the nonxerostomic diabetic patients. The salivary flow rates of the diabetic subjects was consistently lower than those of healthy, nondiabetic control subjects. The mean, resting, and whole-saliva flow rate was abnormally low in the diabetic patients who complained of xerostomia; no significant differences were observed for the stimulated salivary and the lacrimal flow rates. Significant inverse relationships were shown between salivary flow and the level of HbA1; none were shown between flow and autonomic function. CONCLUSIONS: Dry mouth is a common complaint among ambulatory diabetic patients. It is strongly associated with objective measurements of poor salivary flow and with other oral and extraoral symptoms of desiccation. The oral dryness is not associated with cardiovagal autonomic system dysfunction but may be due to disturbances in glycemic control. PMID- 1516512 TI - Foot pressure measurements in diabetic and nondiabetic amputees. AB - OBJECTIVE: Foot problems are common in the remaining foot of diabetic amputees. Because high foot pressures are associated with foot ulceration, we studied foot pressures of the remaining foot of diabetic and nondiabetic unilateral amputees. RESEARCH DESIGN AND METHODS: Four age-matched groups of 11 subjects were studied. The groups were comprised of diabetic subjects with previous major amputation, nondiabetic nonneuropathic amputees, diabetic nonamputee patients with similar peripheral nerve involvement as the diabetic amputees, and nondiabetic control subjects. Vibration perception threshold (VPT) was assessed by biothesiometry and foot pressures with an optical pedobarograph. RESULTS: Mean +/- SE VPT in the diabetic amputees was significantly higher than the nondiabetic amputees (40.2 +/ 3.7 vs. 17.7 +/- 2.8 V, P less than 0.002) and similar to diabetic nonamputees (43.4 +/- 3.3 V, NS). VPT was abnormal in 9 (82%) diabetic amputees, 2 (18%) nondiabetic amputees, and 10 (91%) nonamputee diabetic patients. The mean peak foot pressure in the diabetic amputees was higher compared with nondiabetic amputees (18.3 +/- 2.2 vs. 11.3 +/- 1.4 kg/cm2, P less than 0.05) and control subjects (10.0 +/- 1.5 kg/m2, P less than 0.01), but no difference existed with diabetic nonamputees. Abnormally high foot pressures (greater than 12.3 kg/cm2) were present in 8 (73%) diabetic amputees, 3 (27%) nondiabetic amputees, 8 (73%) diabetic nonamputees, and 4 (36%) healthy subjects. CONCLUSIONS: We conclude that high pressures are present under the remaining foot in diabetic amputees, and that these pressures are associated with diabetic neuropathy. Prosthetic usage does not increase the pressures under the remaining foot in nondiabetic amputees. PMID- 1516513 TI - Prevalence of cardiovascular autonomic dysfunction assessed by spectral analysis and standard tests of heart-rate variation in newly diagnosed IDDM patients. AB - OBJECTIVE: To determine the prevalence of cardiovascular autonomic nerve dysfunction in patients with newly diagnosed insulin-dependent diabetes mellitus (IDDM) compared with healthy nondiabetic subjects. RESEARCH DESIGN AND METHODS: A battery of cardiovascular reflex tests was performed in 130 newly diagnosed IDDM patients aged 12-40 yr at mean blood glucose levels of 7.2 mM after insulin had been administered for 3-39 days. Age-dependent lower limits of normal of these tests were defined at the 2.3 percentile in 120 nondiabetic subjects. Tests of heart-rate variation (HRV) included the coefficient of variation (C.V.) and the low-frequency (LF), midfrequency (MF), and high-frequency (HF) bands of spectral analysis at rest, HRV during deep breathing (C.V., expiratory-inspiratory ratio, and mean circular resultant), Valsalva ratio, and maximum/minimum 30:15 ratio. In addition, spectral analysis on standing, the change in systolic blood pressure to standing, and diastolic blood pressure response to sustained handgrip were determined in 50 patients. RESULTS: A significantly higher percentage of abnormal test responses in the diabetic group compared with the control group was noted for power spectrum in the LF band (7.3 vs. 0.8%, P less than 0.05) and MF band (10.6 vs. 0%, P less than 0.001) at rest and HF band on standing (10.0 vs. 0.9%, P less than 0.05), maximum/minimum 30:15 ratio (25.4 vs. 5.0%, P less than 0.001), and Valsalva ratio (17.5 vs. 4.2%, P less than 0.001). There were no significant differences between both groups in regard to the remaining parameters. Ten (7.7%) diabetic patients but none of the nondiabetic subjects had cardiovascular autonomic neuropathy defined by the strict criterion of abnormal results in more than three of six tests (P less than 0.001). In addition, 12 (9.2%) patients but only 2 (1.7%) control subjects had abnormal results in two of six tests (P less than 0.01). CONCLUSIONS: Cardiovascular autonomic nerve dysfunction is relatively common in newly diagnosed IDDM patients after correction of the initial metabolic imbalance. A combination of tests based on spectral and conventional analysis of HRV appears suitable for detection of early abnormalities in autonomic function in diabetes. PMID- 1516514 TI - Association of waist-hip ratio with diabetes mellitus. Strength and possible modifiers. AB - OBJECTIVE: To characterize the association between central obesity, as measured by the waist-hip ratio (WHR), and non-insulin-dependent diabetes mellitus (NIDDM), considering the effects of sex, age, overall obesity, and family history of diabetes. RESEARCH DESIGN AND METHODS: Case-control study nested within a community-based survey. We selected 151 subjects with NIDDM and 301 nondiabetic control subjects as a systematic sample of survey screening negative individuals. RESULTS: Odds ratios for NIDDM, comparing a high WHR (greater than or equal to 0.926 for men, greater than or equal to 0.83 for women) to a low WHR were 4.72 with a 95% confidence interval of 2.39-9.34, and 2.17 with a 95% confidence interval of 1.03-4.58, for women and men, respectively, controlling for age, overall obesity, and a family history of diabetes. Women with high WHRs in the presence of these risk factors are notably at risk for diabetes. CONCLUSION: Central obesity, as measured by the WHR, is importantly and independently associated with NIDDM. PMID- 1516515 TI - Low incidence of childhood IDDM in district of Novosibirsk (Russia). AB - OBJECTIVE: To study the incidence of insulin-dependent diabetes mellitus (IDDM) among 0- to 14-yr-old children of the district of Novosibirsk, in western Siberia, Russia, from 1983 to 1989. RESEARCH DESIGN AND METHODS: Data were collected with methods recommended by the Diabetes Epidemiology Research International Group. RESULTS: The average yearly incidence among males and females was 4.7 (95% confidence interval 3.9-5.8) and 4.4 (95% confidence interval 3.6-5.4) per 100,000 people, respectively. The incidence of IDDM among children living in the city of Novosibirsk was significantly higher than in children living in the surrounding counties of the district, 5.7/100,000 (95% confidence interval 4.8-6.8) versus 3.6/100,000 (95% confidence interval 2.9 4.5). CONCLUSIONS: The incidence of childhood IDDM among Russians in Siberia is low. This is the first publication of internationally comparable data on the occurrence of childhood IDDM in the Russian population. PMID- 1516516 TI - Antihypertensive therapy for patients with diabetes mellitus. PMID- 1516517 TI - A practical look at patient empowerment. PMID- 1516518 TI - Is thinner always better? PMID- 1516519 TI - Diabetes in Bulgaria. PMID- 1516520 TI - Fluctuations in plasma proinsulin in an insulinoma. Implications for screening test. PMID- 1516521 TI - Do you really get a diet soft drink when you order one? PMID- 1516522 TI - Hypoglycemia induced by enalapril in patient with insulin resistance and NIDDM. PMID- 1516523 TI - Milk allergy masquerading as insulin allergy. PMID- 1516524 TI - Relationship between pancreatic insulin content and serum C-peptide response in diabetic subjects. PMID- 1516525 TI - Refractory changes of the eyes in NIDDM during treatment. Quantitative analysis. PMID- 1516526 TI - Hemodynamic states during normoglycemia and hypoglycemia in a pregnant woman. PMID- 1516527 TI - [Myocardial contrast echocardiography for the follow-up after percutaneous transluminal coronary angioplasty]. AB - Myocardial contrast echocardiography was performed, before and after successful elective percutaneous transluminal angioplasty (PTCA) of a main coronary artery, in 35 patients (31 men, 4 women; mean age 56 +/- 6 years). After intracoronary injection of microbubbles-containing 2 ml iopromide, contrast half-life (t/2) and maximal echo-intensity (Imax) in the myocardial region supplied by the target vessel were measured. While t/2 decreased from 8.3 +/- 5.4 s to 5.7 +/- 3.3 s (P less than 0.0002), mean Imax remained unchanged (27.4 +/- 10.7 vs 26.1 +/- 10.1 grey value units). Repeat cardiac catheterization with contrast echocardiography was performed a mean of 37 weeks (7-53) later in 13 of 35 patients with optimal echo image quality. Re-stenosis of at least 75% was demonstrated in six patients, while in seven vessel diameter had decreased by less than 30%. In all patients with re-stenosis t/2 had increased by about 20 to 100% of the initial value. It was always over 5 s (mean 6.2 +/- 1.6 s before, 4.7 +/- 1.7 after PTCA, and 6.2 +/- 1.2 s at the end of the follow-up). In one patient a prolonged t/2 persisted due to vessel dissection. Mean t/2 remained unchanged in patients without re stenosis (5.6 +/- 2.1 s before, 3.5 +/- 1.15 s immediately after PTCA, and 3.6 +/ 1.25 s at the follow-up examination). These data suggest that contrast half-life is suitable for demonstrating changes in myocardial perfusion after PTCA. PMID- 1516528 TI - [The piezoelectric lithotripsy of gallstones. The acute- and long-term results]. AB - Extracorporeal piezoelectric lithotripsy (PEL) with oral lysis (about 7.5 mg/kg urso- and chenodeoxycholic acid as single dose in the evening) was performed, according to a standardized treatment and follow-up protocol, in 219 patients (177 women, 42 men; aged 47 +/- 14 years) with symptoms of gallbladder stones. The average number of treatment sessions per patient was 2.0 +/- 0.8. Significantly fewer sessions with fewer shockwave charges were required in solitary gallstones of less than or equal to 20 mm diameter than in those of greater than 20 mm diameter and in multiple concrements (P less than 0.01). Fragmentation was successful in 99% of patients. Sedation and/or analgesia during PEL were required in only 2% of patients. There were no marked side effects during the treatment. The stone-free rate 12 months after the start of treatment was 76% in the group with solitary stones less than or equal to 20 mm, 75% with solitary stones greater than 20 mm and 64% for multiple stones. During the follow up period 36% of patients had biliary colics and 3% had fragments impacted in the common bile duct. Biliary pancreatitis occurred in 1% of patients. PEL is an effective and sparing procedure in the treatment of selected patients with gallbladder stones. PMID- 1516529 TI - [Acute aortic insufficiency following endocarditis due to infection with Campylobacter fetus subspecies fetus]. AB - A 50-year-old male alcoholic addict, examined because of diarrhoea with fever was found to have Campylobacter jejuni in blood and stool cultures. After administration of broad-spectrum penicillin all acute symptoms disappeared but he lost 8 kg within 3 months and his general state health gradually deteriorated. After 3 months he suddenly developed leg oedema, dyspnoea and bouts of fever up to 38.8 degrees C. A loud cardiac murmur was now heard. Echocardiography demonstrated vegetations on the regurgitant aortic valve. Endocarditis being suspected he was at first treated with penicillin G (15 mega IU/d) and gentamycin (160 mg/d). The fever regressed, but after 8 days the blood culture grew Campylobacter fetus subspecies fetus. Antibiotic treatment was switched to imipenem, twice daily 500 mg, in accordance with sensitivity test results. Further blood cultures were sterile. Despite this the cardiac status deteriorated, the aortic regurgitation reaching grade IV. The valve was replaced with a bioprosthesis and the patient quickly improved postoperatively. Antibiotic treatment was stopped and the cardiovascular status became normal. The patient has now been free of symptoms and recurrence for 7 months. PMID- 1516530 TI - [Severe tetraparesis as the first manifestation of a chronic lymphatic leukemia]. AB - Uncertain gait and weakness on standing, progressing to flaccid paraparesis of both legs, developed in a 76-year-old woman. Proprioceptor reflexes of both legs were absent and there was pallaesthesia up to the pelvic rim. Electromyography pointed to polyneuritis. Administration of prednisone, 1 mg/kg daily for 10 days, was ineffective, as was one-time plasmapheresis. An incomplete tetraparesis developed. Blood white-cell count increased within 2 weeks by 10,400/microliters (52% lymphocytes) to 17,400/microliters. Blood smear, bone-marrow cytology and histology, as well as immunocytology, revealed lymphoplasmocytoid immunocytomas (chronic lymphocytic leukemia). Oral cytoreductive treatment was started with chlorambucil, 0.1 mg/kg daily, and prednisone, 100 mg daily. After 19 days the patient was able to walk with support, after 28 was walking unaided. Treatment was continued over eight cycles (14 days' treatment, 14 days' interval per cycle). 17 weeks after onset of treatment paraesthesias of the legs required renewed administration of chlorambucil, 0.1 mg/kg per day, for 3 months. The patient has now been free of symptoms during a follow-up period of 12 months. PMID- 1516531 TI - [Acute and chronic urticarias]. PMID- 1516532 TI - [Amyloidosis of the respiratory tract]. PMID- 1516533 TI - [The therapy of Salmonella enteritis]. PMID- 1516534 TI - [Multifocal leukoencephalopathy following adjuvant therapy with fluorouracil and levamisole]. PMID- 1516535 TI - [The knowledge base and length of time of medical practice]. PMID- 1516536 TI - [The effect of heavy metals on the in vitro interaction between human sperm and cervical mucus]. AB - The sperm-cervical mucus-penetration test (SCMPT) was used in vitro to examine the influence of heavy metals (mercury, cadmium and copper) on sperm function. 30 each of freshly obtained different sperm samples with varying starting sperm motility and oestrogen-stimulated cervical mucosa from women of known fertility were used. Mercury chloride (HgCl2; 0.005-0.5 mmol/l), cadmium chloride (CdCl2; 0.05-10 mmol/l) and copper sulphate (CuSO4; 0.0001-10 mmol/l) were added to the in-vitro system. After incubation, at 37 degrees C for 6 hours, linear progression, penetration depth and motility index of the sperm (cumulative SCMPT score) were analysed. An untreated control was run in parallel with each test. The added substances, especially CdCl2 and HgCl2, significantly reduced the quantitative and qualitative penetrability of sperm (P = 0.001), in step with the concentration. The concentrations which were used, especially those of mercury, were in the range of in-vivo. measured levels. These results make clear that heavy metals can influence human sperm function. PMID- 1516537 TI - [Cholesterol--a marker for multiple risk factors? A comparison between coronary disease and coronary health]. AB - Comparison was made in a cross-sectional study between 658 patients in whom coronary arteriography had shown (n = 304) or excluded coronary artery disease (CHD) (n = 354) and a clinically healthy group as controls (n = 1658), to assess possible risk factors. Patients aged 31-40 years with CHD had the highest total cholesterol levels (286 +/- 43 mg/dl) and the highest number of risk factors (3.6 +/- 0.9) compared to patients without CHD of the same age (204 +/- 30 mg/dl; 2.0 +/- 0.5) and healthy controls (216 +/- 45 mg/dl; 1.7 +/- 0.5) (P less than 0.001). In older patients with CHD, total cholesterol levels were lower (age group 61-70 years: 231 +/- 49 mg/dl), reaching about the same level as that of patients without CHD (232 +/- 54 mg/dl) or healthy controls of the same age (228 +/- 55 mg/dl). Furthermore, it was demonstrated that increased total cholesterol concentration can indicate the presence of other risk factors. It would thus appear that the level of total cholesterol in patients with CHD is decisively influenced by age and the presence of other risk factors. PMID- 1516538 TI - [Pacemaker implantation via a persistent left superior vena cava in atresia of the true superior vena cava]. AB - Implantation of a single-chamber pacemaker was planned in an 83-year-old woman with sick-sinus syndrome causing dizziness, bradycardia and tachycardia. After puncture of the right subclavian vein it proved impossible to advance a guide wire into the superior vena cava, under fluoroscopy the wire always being seen to coil in the left subclavian vein and hence passing into a caudally directed vein. This vessel proved to be a persistent left superior vena cava (PLSVC) which connected to a markedly dilated coronary sinus (2 cm diameter) opening into the right atrium. An 85-cm electrode was then passed via the PLSVC and right atrium into the right ventricle without difficulty and was anchored in its apex. Echocardiography failed to reveal any further anomaly. Three-dimensional computed tomographic reconstruction established atresia or agenesis of the (right) superior vena cava. Normal pacemaker function freed the patient of all symptoms postoperatively. PMID- 1516539 TI - [Press reports about physicians and medical advertising ban. Decision of the federal constitutional court on February 11, 1992]. PMID- 1516540 TI - [Ascites puncture]. PMID- 1516541 TI - [Therapy of urogenital tuberculosis]. PMID- 1516542 TI - [Fluorescing light ring from the fair]. PMID- 1516543 TI - [Table salt and blood pressure]. PMID- 1516544 TI - [Veterinary medicine and environmental hygiene--20 years of seminars on environmental hygiene]. AB - The changes of the environment after industrialization since 1965 influenced some political decisions concerning a critical evaluation of such development which may injure the environment. The School of Veterinary Medicine Hannover discussed in that time how the problems could be met by establishing a postgraduate stadium of environmental sciences. These ideas were realized, starting with seminars in the first year for one week, later for one or two days periods (Table). Postgraduate students and interested veterinarians with questions arising from their occupation participated in the seminars. The main topics of the seminars referred to effects of chemical, physical and biological influences from the environment upon farm animals and vice versa that part of animal housing which is involved in the harmful changes of the environment. PMID- 1516545 TI - [Environmental hygiene tasks of the veterinarian in practice]. AB - Apart from his direct tasks like treating diseased animals, preservation of animal health, recognition of mal-feeding and failures, recognition of unsuitable keeping systems and acknowledgement of animal welfare the veterinary practitioner can be the environmental-hygienic consultant of the farmer in following areas in particular: management and technique of feeding; management and technique of water supply; management and technique of air quality and ventilation; management and technique of manure handling and hygiene; cleaning and disinfection; deratting and pest control. The aim of these tasks is to diminish the risks/hazards for food products (food control act), the air (emission control act), surface water (law on the water household), ground water (waste control act, law on the water household) and vegetation and soil (waste control act, nature conservation act). Some examples will be given and comments are made on how to run a practice in an environmentally friendly way. PMID- 1516546 TI - [Tasks of public veterinary affairs in environmental hygiene]. AB - The involvement of official veterinarians in tasks of environmental hygiene is demonstrated under differentiation of the following working-fields: animal waste removal, animal health protection, animal welfare, and controlling of foods of animal origin. Thereby it results that nearly all sections of public veterinary affairs are connected with environmental aspects to a high degree. PMID- 1516547 TI - [Requirements for the education, continuing education and additional education in the area of veterinary environmental hygiene]. AB - In view of the future of our profession it is required urgently to improve the education, continue studies and special training in the field of veterinarian environmental hygiene energetically. At this the both subjects "Animal hygiene" and "Foodstuffs hygiene" combined with the epidemiology are the central nucleus. To make plain the veterinarian engagement in this field it is proposed to introduce, a lecture in ecology and to designate the subject "Animal hygiene" in future as "Environment and animal hygiene". PMID- 1516548 TI - [Research in veterinary environmental hygiene]. AB - The course of development of the initial subject "Veterinary Hygiene" to the reduction and specialization limited to "Animal Hygiene" and the recent extension into the broad field of environmental hygiene is described. This is done with reference to books and other publications which point the way ahead for research of veterinary medicine in environmental hygiene and thus prove the increasing importance of that subject. A survey is given over current German research in that field, future demands as well as the necessary extension of environmental hygiene in graduate and post-graduate teaching of veterinary students as well as further professional training of veterinarians. PMID- 1516549 TI - [Changes in the dynamics of viral infectious diseases]. AB - Modern methods of molecular biology are suitable to analyse evolutionary processes in the area of infectious diseases. Visible expression of this evolution is the emergence of "new" infectious agents, e.g., canine parvovirus, the agent of the porcine reproductive and respiratory syndrome and phocine distemper virus. In addition a gradual change of disease syndromes may be observed, e.g., classical and African swine fever and myxoma. These processes are based on genomic changes of the respective infectious agents, i.e., point mutations and recombinations. Especially RNA viruses are prone to genomic change, and the plasticity of their genomes enables them to adapt to varying selective pressures. Human activities in agriculture, global commerce and tourism may enhance and precipitate microbial evolution. PMID- 1516550 TI - [Environmental hygienic aspects of echinococcosis]. AB - A literature review on the current situation of echinococcosis in Central Europe is given. The only final host for Echinococcus granulosus in this region ist the dog. The infection rate of dogs with E. granulosus in Central Europe is less than 1%. According to meat inspection statistics in Germany less than 0.008% of sheep, pigs and horses carry larval stages of E. granulosus. Parasitologically confirmed is the occurrence of a cattle-dog strain, the cysts of which were found in 0.26% of slaughter cattle. It is not known whether this strain infects also man as does the sheep-dog strain. Cases of cystic echinococcosis (E. granulosus) diagnosed in Central Europe are often imported from mediterranean countries. In Baden Wurtemberg, the only state where human cases of echinococcosis are recorded, 50 100 cases are diagnosed per year. In areas with endemic E. multilocularis infection also dogs and cats may be infected with the adult worm besides the red fox. Recent investigations have revealed that not only in classical endemic areas (Switzerland, Austria, Baden-Wurtemberg, Rhineland-Palatinate) foxes have infection rates of up to 67% but that E. multilocularis-infection is also wide spread in Thuringia, Hesse, Northrhine-Westphalia and in the southern parts of Lower Saxony. The most northern infested area seems to be the region of Detmold (infection rate of foxes 9%). The infection rates with alveolar echinococcosis (E. multilocularis) in humans even in endemic areas are low. In Baden-Wurtemberg 140 new cases became known during the past ten years.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1516551 TI - [Environmental and food hygiene aspects of cestode infections of humans]. AB - Cysticercus bovis s. inermis, the larvae phase of Taenia saginata is still widely spread. Many reasons are at the origin thereof, e.g. incomplete destruction of the eggs of Taenia saginata during the waste water purification process and differing meat inspection practises. In an area with the same environmental and animal breeding and fattening conditions a yearly average of 6.49% infestation is found in one slaughterhouse, whilst the yearly average in a neighbouring slaughterhouse is 0.93%. The masseter muscles are the main site of infestation. The meat inspection legislation contributes to the infestation with tape-worms in man because of the weakening of the official inspection procedures. PMID- 1516552 TI - [The effect of ecotoxicological processes on animal husbandry in industrial countries]. AB - This paper describes results of ecotoxicological investigations concerning the effects of industrial pollutants on farm animals. By means of simultaneous experiments using dusts from lignite-filters and sedimentation-filters as well as sulfur dioxide (SO2) as stress models and by using studies on farm animals in pollutant-burden regions of eastern Germany it could be shown, that pollutants can lead to disorders of health, efficiency and behaviour, like o. g. heavy metals, and to contamination of food of animal origin. Dusts, resulting from combustion of lignite and SO2 initiate non specific effects in the organism and it is only difficult to determine their part on the decrease of productivity and metabolic disorder of farm animals in pollutant regions. PMID- 1516553 TI - [Veterinary tasks in nature and species protection]. AB - The present paper is designed to give examples of possible fields of activities for veterinary surgeons in the areas of nature conservation and the protection of species. The committed veterinary surgeon, who is eager to extend his/her specialized knowledge obtained at the university will certainly find a sensible and satisfying occupation in the fields of nature conservation, the protection of species and the environment. Creating the optimum prerequisites for these professional opportunities is yet another reason why public funding of the Institute for Game Research and Ecology is indispensable. PMID- 1516554 TI - [Cooperation of veterinarians in legislation in the area of environmental hygiene (Germany and the European Economic Community)]. AB - After a brief exposition of the tasks about the protection against chemical, physical, and biological environmental risks, a demonstration will be given according to deliberations of our law system about the possibilities for veterinarians to cooperate in the legislative branches. A detailed examination on former activities in the fields of pollution and the food-chain are to serve as a model for the future legislative process in Germany with the intention to strive for a harmonization of the in parts independently developed legislative branches. The external harmonization, a long-term objective, is to be found in the form of an uniform environmental law. Veterinarians take a great interest to work in advance for this uniform law in the way they bring new perspectives by cooperating in the fields of environmental hygiene and toxicology for the protection of the environmental media, of species and the food-chain. In conclusion one finds a brief documentation about the impact of the adaptation of law and the process on the EC-level. PMID- 1516555 TI - [The effect of bacterial interference phenomena in experimental Staphylococcus hyicus infections of gnotobiotic piglets]. AB - The prevention of exudative epidermitis could be confirmed in experimental investigations with gnotobiotic piglets when the skin first was colonized with avirulent strains of Staphylococcus (Staph.) hyicus and subsequently exposed to virulent strains of Staph. hyicus. However, locally restricted cutaneous lesions in the area of application corresponding to exudative epidermitis were seen in five of nine piglets. Using the strain Staph. sciuri the spread of virulent Staph. hyicus could not be suppressed. Such infected two piglets developed generalized exudative epidermitis. In another experiment with four piglets it could be shown, that the relative protective mechanism correlating to bacterial interference on the one hand can be influenced by the virulence of causative organisms. On the other hand it even can be abolished when skin lesions are involved. For that reason probably the utilization of bacterial interference in prevention of exudative epidermitis under field conditions is considerably limited. PMID- 1516556 TI - Protein interactions in the calf eye lens: interactions between beta-crystallins are repulsive whereas in gamma-crystallins they are attractive. AB - Non-specific interactions in beta- and gamma-crystallins have been studied by solution X-ray scattering and osmotic pressure experiments. Measurements were carried out as a function of protein concentration at two ionic strengths. The effect of temperature was tested between 7 degrees C and 31 degrees C. Two types of interactions were observed. With beta-crystallin solutions, a repulsive coulombic interaction could be inferred from the decrease of the normalized X-ray scattering intensity near the origin with increasing protein concentration and from the fact that the osmotic pressure increases much more rapidly than in the ideal case. As was previously observed with alpha-crystallins, such behaviour is dependent upon ionic strength but is hardly affected by temperature. In contrast, with gamma-crystallin solutions, the normalized X-ray scattering intensity near the origin increases with increasing protein concentration and the osmotic pressure increases less rapidly than in the ideal case. Such behaviour indicates that attractive forces are predominant, although we do not yet know their molecular origin. Under our experimental conditions, the effect of temperature was striking whereas no obvious contribution of the ionic strength could be seen, perhaps owing to masking by the large temperature effect. The relevance of the different types of non-specific interactions for lens function is discussed. PMID- 1516557 TI - Dantrolene inhibits halothane-induced membrane reorganization. A study using 31P NMR and differential scanning calorimetry. AB - The action of the relaxing agent dantrolene on dipalmitoylphosphatidylcholine (DPPC) model membranes in the presence and absence of the general anesthetic halothane has been investigated by DSC and 31P-NMR. Dantrolene has a weak effect on both the thermodynamic and NMR parameters of the pure model membrane. When halothane is present in the system, the relaxing agent acts to counterbalance the strong anesthetic-induced membrane perturbation. This is reflected in DSC experiments by a change of the enthalpy variation (delta H) and of the main gel to-fluid phase transition temperature (Tc) towards the values of the pure lipid system. The amount of halothane-induced small tumbling vesicles, as detected by 31P-NMR by the superposition of an isotropic line on a lamellar-type powder spectrum, is considerably reduced upon dantrolene addition. This means that the relaxing agent "cures" the membrane de-structuring action promoted by halothane. Membranes first treated with dantrolene are also protected from the halothane perturbation. So, the relaxing agent is both "curative" and "preventative" against halothane. The optimum effect is obtained for 1 dantrolene molecule per ca 34 halothane molecules. The mechanisms of action were discussed in relation to membrane fluidity. PMID- 1516558 TI - Reactions in lipid vesicles. Pyrene excimer formation in restricted geometries. Effect of temperature and concentration. AB - The decay of pyrene in the presence of excimers in small unilamellar vesicles of 3-sn-phosphatidyl glycerol, dipalmitoyl and 3-sn-phosphatidylglycerol from egg yolk has been analyzed with the use of models appropriate for reactions in restricted geometries. Results are presented with emphasis on probe concentration and temperature. The reaction rate in an organized lipid phase is redefined in a simple manner which allows for a simple treatment of any reaction in such environments. The analysis allows detection of pyrene aggregation in the vesicle lipidic core. PMID- 1516559 TI - Formation of cell protrusions by an electric field: a thermodynamic analysis. AB - This work gives a thermodynamic analysis of outgrowth extraction from the cell body by a pulling force. The results are applied for a case when the pulling force is generated by an external high-frequency electric field. Two equilibrium conditions are analyzed: internal equilibrium of an outgrowth and equilibrium between the outgrowth and the cell body. In both cases the stability of feasible equilibrium states was studied. The work shows that the curvature of an outgrowth equilibrated with a pulling electric force depends on the squared amplitude of the electric field E0(2), on the outgrowth length l and on the transmembrane pressure differential delta P, and that at a sufficiently large transmembrane pressure differential the cylindrical form of the outgrowth loses its stability. Long outgrowths are more stable than short ones. The minimal value of critical pressure differential was estimated. The work also shows that outgrowth extraction from the cell body requires that the applied force exceeds a critical value below which no outgrowth is formed. The value of the electric field at which outgrowth formation is feasible was estimated. PMID- 1516560 TI - Determination of the partition of the tetramisole derivative (+-)-5,6-dihydro-6 phenyl-2-n-propyl-imidazo[2,1-b]thiazole into liposomal membranes by fluorescence quenching of the membrane probe 8-(2-anthryl)-octanoic acid. AB - Fluorescence quenching has been used to study the partition of the tetramisole derivative (+-)-5,6-dihydro-6-phenyl-2-n-propyl-imidazo[2,1-b]thiazole into liposomes, consisting of a mixture of egg L-alpha-phosphatidylcholine, egg phosphatidylethanolamine and dipalmitoylphosphatidic acid (2:1:0.06 w/w/w). The tetramisole derivative quenched the fluorescence of the intramembrane probe 8-(2 anthryl)-octanoic acid. The quenching process could be rationalized by a model for dynamic quenching in which an intermediate excited-state non-emitting complex (PQ)* between neutral quencher (Q) and excited probe (P*) is involved: [sequence: see text] where kd, k-d and ki represent the rate constants of complex formation, dissociation and deactivation, respectively. The subscripts A and L denote the aqueous and lipid phases, and the asterisk indicates the excited state. Linear Stern-Volmer plots were obtained from quenching experiments of fluorescence intensities and fluorescence life-times. The slopes of the plots were dependent on the lipid volume fraction of the liposomes. Measurement of the reciprocal of the apparent bimolecular quenching rate constant at various lipid volume fractions yielded the partition coefficient Kp and the overall quenching rate constant kq[kq = kdki/(ki+k-d)] of the tetramisole derivative. The steady-state measurements were performed at three different pH-values. Time-correlated single photon counting measurements revealed a single-exponential fluorescence decay for 8-(2-anthryl)-octanoic acid in the presence and absence of quencher. The quenching results were in accordance with the model that only the neutral form is capable of partitioning into the lipid phase. Combined average values of 318 and 6.59 x 10(8) M-1s-1 were calculated for the partition coefficient and the bimolecular quenching rate constant, respectively, from the steady-state and time resolved quenching experiments. PMID- 1516561 TI - Conformational transition of an alpha-helix studied by molecular dynamics. AB - Molecular dynamics simulations were performed on a 20-residue polyalanine helix and a spontaneous transition from a kinked to a straight conformation was observed. The kinetics of the transition was analyzed within the framework of the Kramers model for chemical reactions and within a random walk model. The Kramers model which is based on diffusion along a one-dimensional reaction pathway and the crossing of an energy barrier was found to be inadequate. Instead, a random walk model based on diffusion in the high-dimensional phase space of the system was found to be compatible with the data. The high dimensionality of the phase space permits the system to circumvent high energy barriers and diffuse rapidly at about constant energy, but decelerates the reaction since in the labyrinth of pathways the transition state is reached rarely. PMID- 1516562 TI - Scanning calorimetric studies of the stability of tobacco mosaic virus and aggregates of its coat protein. AB - The thermal denaturation of the common strain of a rod-shaped plant virus, tobacco mosaic virus, has been investigated by differential scanning calorimetry, and compared to that of various aggregation states of its coat protein and to that of three other TMV strains. The state of the virions was monitored by electron microscopy and analytical ultracentrifugation. The observed endotherms could be analysed in terms of a step-wise dissociation of the virions. The transition temperatures of the three successive structural changes increased with decreasing pH, from pH = 8.0 to pH = 5.0, although the corresponding enthalpy changes did not vary appreciably with pH. TMV-HR showed a stronger pH dependence of the transition temperatures than the other strains, probably reflecting the importance of the changes in affecting the charged amino acids of its coat protein. The first step of the dissociation, which correlates with the breaking up of the virions into three or four shorter rods, implies a conformational change of the particle that may be related to the first step of the in situ decapsidation of TMV. PMID- 1516564 TI - Stimulation of Candida albicans transition by human chorionic gonadotrophin and a bacterial protein. AB - Candida albicans, a dimorphic fungus, is involved commonly in human infections with the mycelium form more associated with pathogenicity. The influence of various hormones and a bacterial protein on the transition from blastospore to mycelium was assessed. Human luteinizing hormone (hLH), chorionic gonadotrophin (hCG), and an hCG-like material purified from a bacteria, Xanthomonas maltophilia (PCG), were able to increase the rate of transition when compared with the controls. The effect of the two hormones and the bacterial peptide were specific, as human follicle stimulating hormone (hFSH), thyroid stimulating hormone (hTSH), growth hormone (hGH), prolactin (hPrl) and rat and bovine LH (rLH, bLH), and bovine albumin and gamma globulin did not affect the transition. The binding of 125I-hCG or 125I-LH to spheroplasts of Candida albicans were competitively displaced by hCG, hLH, and PCG. Scatchard analysis of binding of all three ligands revealed two binding sites with a high-affinity nM Kd. Thus, hCG, hLH, and PCG induce transition of Candida albicans from a blastospore state to a mycelium form, suggesting that these hormones may modify the pathogenicity of Candida albicans. PMID- 1516563 TI - Renal and adrenal responsiveness to angiotensin II: influence of beta adrenergic blockade. AB - The increase in aldosterone secretion that occurs in response to Angiotensin II (AII) is enhanced when normal humans are in external balance on a low salt diet. The responsible mechanism has not been identified. Angiotensin converting enzyme inhibition reduces blood levels of AII and aldosterone, but does not decrease PRA or AI and does not modify adrenal responsiveness to AII in the sodium-depleted state. This study was designed to assess the possibility that the enhanced adrenal response reflects plasma renin activity (PRA), plasma AI concentration, or catecholamines acting via a beta adrenergic receptor. Nine healthy males were studied when in balance on a high sodium intake (200 mmol Na/day), a low sodium diet (10 mmol Na) and after 4 days of beta adrenergic blockade with either nadolol or propranolol. The adequacy of beta adrenergic blockade was assessed with a postural stimulus and significant blockade was achieved, somewhat more with nadolol (40 mg/day) than with propranolol (Inderal LA, 80 mg every 12 hrs). Beta blockade enhanced the renal vascular and pressor response to AII but did not modify the adrenal response to posture or to AII. This study confirms the role for AII levels in the modulation of renal vascular and pressor responses to AII and rules out a role for PRA, AI, or catecholamines acting via a beta adrenergic receptor in the modulation of adrenal responsiveness to AII. PMID- 1516565 TI - A brief survey of pineal gland-immune system interrelationships. AB - The present paper summarizes evidence that support the hypothesis of the existence of bilateral interactions between pineal gland and the immune system. Both in vivo and in vitro experiments show that the pineal gland, via its hormone melatonin, enhances immune function. Mechanisms involved in this immunostimulatory effect are not well understood, but some evidence suggests the existence of specific binding sites for melatonin on immune cells. Moreover, the release of opioid peptides and interleukin-2 by T-helper cells may also participate in this mechanism by activating, at least natural killer activity and antibody-dependent cellular cytotoxicity. Some immune signals, i.e., gamma interferon, may be involved in regulating pineal function, thereby representing a regulatory mechanism in the opposite direction. The physiological and clinical significance of these data remains to be studied. PMID- 1516566 TI - Alveolar and interstitial macrophage populations in the murine lung. AB - Pulmonary macrophages (PM) exist in two general anatomical compartments in the lower respiratory tract: the alveolar space (alveolar macrophages, AM) and the interstitium (interstitial macrophages, IM). We determined the relative contribution that macrophages in each of these compartments make to the size of the total PM population found in the lungs of C3H/OUJ mice, while also evaluating how efficiently bronchoalveolar lavage (BAL) removes AM from the murine lung. These objectives were accomplished by combining extensive BAL with subsequent mechanical and enzymatic dissociation of the lungs in conjunction with in situ and in vitro phagocytic assays involving opsonized erythrocytes (EA) to identify mononuclear phagocytes. On average, 2.5 x 10(6) cells were recovered by extensive BAL, and approximately 78% of these cells ingested EA in vitro. To determine the efficiency of BAL in removing PM from the alveolar space, EA were instilled intratracheally into intact lungs, which had been removed from the chest cavity, and allowed to incubate for 60 min; this was followed by exhaustive BAL and subsequent lung digestion. After these procedures, approximately 4% of the dissociated lung cells contained EA, indicating that these cells were alveolar in origin but had not been removed despite extensive BAL. Subtraction of these AM from the total EA+ cells in lung cell suspensions following a second in vitro incubation with EA indicated that approximately 37% of all PM were within the interstitium. These results suggest that, while AM comprise the majority of lung macrophages, IM constitute a larger component of the total PM population in murine lungs than previously reported. In addition, this study, like several previous investigations using other species, indicates that a significant proportion of AM remain in the lung despite attempts to remove them with BAL. Accordingly, residual AM significantly contaminate the IM population present in murine lung cell suspensions even after extensive lavage. PMID- 1516567 TI - Dynamic changes in the functional characteristics of the interstitial fibroblast during lung repair. AB - To evaluate the mechanisms involved in the regulation of fibroblast function during the repair of fibrotic lung injury, we isolated lung fibroblasts from adult male Fischer-344 rats before the induction of severe unilateral paraquat lung injury, as well as 1 and 14 days later. Fibroblasts were utilized at an early generation time to avoid senescence. In general, fibroblasts of injured lungs displayed significant increases in proliferative and matrix synthesis properties, with more pronounced increases detected early after the induction of injury. This was true of DNA synthesis, which increased by 3- and 1.4-fold on days 1 and 14, respectively; tyrosine kinase activity, which increased by 4- and 3.5-fold; fibronectin synthesis, 14- and 8-fold, respectively; and glycosaminoglycans synthesis, 4.4- and 3-fold, respectively. The increase in function of fibroblasts isolated from the immediate influence of extrinsic growth factors suggests that fibroblast function during repair may be under intrinsic as well as extrinsic control. In the early phases of repair, intrinsic changes may be more dominant and may result in autoregulation of fibroblast function. In the later phases of repair, despite some reduction in intrinsic fibroblast activation, exposure to extrinsic growth factors may result in maintaining the state of activation and in sustaining the repair process. PMID- 1516568 TI - Morphometric comparisons of rat alveolar macrophages, pulmonary interstitial macrophages, and blood monocytes. AB - Pulmonary interstitial macrophages (IM) account for a substantial fraction of the total pulmonary macrophage (PM) population in the mammalian lung, with the remaining balance of extravascular mononuclear phagocytes being mainly alveolar macrophages (AM). Unlike the AM that can be harvested readily by bronchoalveolar lavage, the lung's IM subpopulation of PM has been characterized less well, primarily because of its relative inaccessibility. Recently we developed a method to isolate viable IM from rat lungs using an Fc gamma receptor affinity technique in conjunction with multiparameter flow cytometry. Using this approach, we undertook the present investigation to characterize quantitatively the structural features of the IM and to compare the morphologic attributes of this subpopulation of PM to those of flow cytometrically sorted AM and blood monocytes (BM). Measured or calculated parameters for each population included mean cellular equivalent circular diameter, cell area and volume, and nuclear, mitochondrial, cytoplasmic, and lysosomal volume densities in each cell type. Lysosomal volume densities were subcategorized further into primary lysosomes, small secondary lysosomes, large secondary lysosomes, lipid droplets, and vacuoles. Additionally, the shape, form, and surface irregularity of the cells and various subcellular components were determined. Comparisons of the size and other structural features of the AM, IM, and BM have indicated that (1) the morphologic phenotypes of these three populations of mononuclear phagocytes distinctly differ from one another, (2) the IM and BM are morphologically and morphometrically more akin to one another than they are to AM, and (3) the IM are more similar to the AM than are the BM. These findings suggest that the IM may represent a transitional stage of maturation between BM and AM. Our findings, however, do not rule out the possibility that at least some of the lung's IM are a discrete, BM-independent population of macrophages. PMID- 1516569 TI - Three-dimensional reconstruction of tubular myelin. AB - The lipid and protein components of pulmonary surfactant are synthesized by alveolar type II cells and stored in their secretory granules, the lamellar bodies. Tubular myelin is a highly ordered surfactant structure that is lung specific and produced in the alveolar airspace. Recent work identified Ca2+, surfactant apoproteins A and B, and saturated phospholipids as necessary for tubular myelin structure and function. We have used serial ultrathin sections from fetal rat lungs and reconstructed the three-dimensional structure of tubular myelin. The spheres of tubular myelin we viewed were 2-3 microns in diameter and were surrounded by up to 20 lamellar bodies, each apparently simultaneously contributing material to the tubules. We measured a long-range symmetry of the tubules, which were folded about a central axis and showed a repeated crossing of individual tubes from one side to the other of the large structure. The tubes appeared closed on their outer edges and there was a delay in the penetration of tubules by cationic ferritin added to tissue slices containing the tubular myelin, although within a few minutes tracer appeared in the lumina and on the walls of the tubules. The three-dimensional images were compatible with existing views of tubular myelin. PMID- 1516570 TI - Long-term intermittent exposure to sulfuric acid aerosol, ozone, and their combination: alterations in tracheobronchial mucociliary clearance and epithelial secretory cells. AB - Understanding the effects from long-term exposure to individual ambient air pollutants and mixtures of pollutants is necessary for adequate assessment of health risk. This study examined quantitative and temporal alterations in tracheobronchial mucociliary clearance function and bronchial epithelial secretory cells in rabbits exposed to sulfuric acid (125 micrograms/m3), ozone (0.1 ppm), and their combination for 2 h/d, 5 d/wk for up to 1 yr; some animals were allowed a 6-month post-exposure period. Clearance times were altered during exposure to sulfuric acid or to the mixture, and became progressively slower following the end of exposures to each of the pollutant atmospheres. There was no indication of any interaction in terms of clearance response between the acid and ozone in the group exposed to the mixture. Histological examination of intrapulmonary conducting airways was performed after 4, 8, or 12 months of exposure, and after the post-exposure period. Sulfuric acid resulted in an increase in the number of secretory cells in small airways by 12 months of exposure. Ozone and the mixture resulted in an increase in secretory cell number by 4 months, but the response became attenuated with continued exposure. There was evidence for synergistic interaction between ozone and acid at 4 months, and antagonistic interaction at subsequent times. No inflammation or other biologically significant histological effects were found in any of the animals. PMID- 1516571 TI - Protein kinase C activation modulates arachidonic acid metabolism in cultured alveolar epithelial cells. AB - Cultured alveolar type II cells can liberate esterified arachidonic acid (AA) and metabolize it predominantly via the cyclooxygenase pathway, and their capacity to do so increases as they alter their phenotype over time in culture. Little is known, however, about the regulation of AA metabolism in alveolar pneumocytes. We have examined the effects of protein kinase C (PKC) activation on arachidonate metabolism in primary cultures of rat alveolar epithelial cells studied at 2 and 7 days following isolation. The potent PKC activator phorbol myristate acetate (PMA) stimulated dose-dependent increases in free AA levels in both day 2 and day 7 cultures, with optimal stimulation at 50 nM. Greater stimulation was demonstrated for day 7 cells, and this was associated with greater prostanoid synthesis in response to PMA by day 7 than by day 2 cells. The capacity of PMA to "prime" epithelial cells for augmented AA liberation and metabolism in response to calcium ionophore A23187 (5 microM) was examined also. Significant priming by PMA was observed in both day 2 and day 7 cells; once again, augmentation of both free AA levels as well as prostaglandin E2 levels was greater for day 7 cells than for day 2 cells. That the capacity of PMA to modulate AA metabolism was mediated by activation of PKC was confirmed by demonstrating that (1) phorbol didecanoate, which lacks the ability to activate PKC, failed to activate AA metabolism; (2) pretreatment for 18 h with 1 microM PMA, which depletes cellular PKC, abolished subsequent AA metabolism activated by 50 nM PMA; and (3) the PKC inhibitor staurosporine abrogated increases in the quantities of both free AA and prostaglandin E2 in response to PMA. We conclude that activation of PKC increases the availability of AA for prostanoid synthesis in alveolar pneumocytes, and that this effect is more evident as type II cell differentiation is modeled during prolonged cultivation. PMID- 1516572 TI - Soluble beta-galactoside specific lectin is developmentally regulated in lungs of neonatal black mice and beige mice. AB - The beige mouse, a mutant of the C57 black mouse, is best known as a model of the Chediak-Higashi syndrome. Recently, it was found that alveolar maturation in neonatal beige mice is impaired, resulting in abnormally large alveoli. In guinea pigs, hamsters, and rats there is an elevated activity of a soluble, beta galactoside-binding lectin in lungs at the age when alveolar maturation is in progress. Our present studies were done to find out if the temporal relationship between elevated lectin activity and alveolar maturation also occurs in mice and, further, if the impaired alveolar maturation in beige mice might be linked to the lectin. We found that the temporal relationship between lectin activity and alveolar maturation is also present in black and beige mice, with a peak in specific lectin activity occurring at about 8 days after birth. We also found that the major lectin purified from black or beige mice has essentially the same subunit molecular weight, isoelectric point, and amino acid composition. In conclusion, we found nothing abnormal about the lectin or its developmental regulation that can explain the impaired alveolar maturation in neonatal beige mice. The results do not rule out the possibility of an important role for the lectin in normal lung development or the possibility that some aspect of function or localization of the lectin or its ligands, not related to total lung lectin hemagglutinating activity, may be altered in the beige mouse. PMID- 1516573 TI - Phosphatidylcholine synthesis, secretion, and reutilization during differentiation of the surfactant-producing type II alveolar cell from fetal rabbit lungs. AB - Evidence indicates that pulmonary pool sizes of choline and related intermediates available for synthesis of phosphatidylcholine, the major component of the surfactant, change during gestation. Furthermore, recent data suggest that the type II lung cells that produce the surfactant potentially can reutilize components of this material. However, the relationship of the de novo synthetic mechanism to the secretion and reutilization of phosphatidylcholine has not been established. This is particularly true in the case of the fetal lung where, although alterations in precursor pool sizes, including choline, have been demonstrated, few or no data are available concerning how phosphatidylcholine synthesis affects or is affected by secretion and reutilization of this phospholipid by fetal type II cells. The present study was undertaken to determine the effect of availability of choline on de novo synthesis of phosphatidylcholine by isolated fetal rabbit type II cells during the differentiation process. In addition, differentiating type II alveolar cells were used to examine the hypothesis that these cells incorporate phospholipid from the extracellular environment and the quantity and/or composition of this phospholipid differently affects cellular secretion or de novo phosphatidylcholine synthesis. Assuming that the cells did not discriminate between radioactive and nonradioactive choline, elevation of extracellular choline increased the synthesis of cellular phosphatidylcholine and disaturated phosphatidylcholine in a dose-dependent manner to 0.08 mM choline. Cells induced to differentiated by exposure to fibroblast-conditioned medium synthesized more total and disaturated phosphatidylcholine at all extracellular choline concentrations. Incubation of the fetal type II cells with dipalmitoylphosphatidylcholine or 1-palmitoyl-2-oleoylphosphatidylcholine significantly depressed the incorporation of [3H]choline into cellular phosphatidylcholine after 24 or 48 h, but not necessarily at both times. Dipalmitoylphosphatidylcholine depressed the secretion of [3H]choline-labeled phosphatidylcholine after incubation for 24 h. 1-Palmitoyl-2 oleoylphosphatidylcholine stimulated the secretion of tritium-labeled phosphatidylcholine at a concentration of 25 micrograms/mL after 48 h. Comparison of the phospholipid effect by incubating the cells with 50 ng of 14C-labeled phospholipid for 24 h showed that 1-palmitoyl-2-oleoylphosphatidylcholine significantly reduced the synthesis of 3H-labeled phosphatidylcholine compared to dipalmitoylphosphatidylcholine. In contrast, 1-palmitoyl-2 oleoylphosphatidylcholine stimulated secretion of 3H-labeled phosphatidylcholine compared with the disaturated moiety. The differentiation state of the cells altered the magnitude of the cellular secretion response but not the character.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1516574 TI - Integrating human factors with the Jackson System Development method: an illustrated overview. AB - The motivation for integrating human factors with structured systems analysis and design methods has been set out in earlier papers. In addition, a preliminary conception of such an integration has been proposed for the Jackson System Development method (referred to as JSD*), and a set of requirements, research and strategies suggested for further developing this conception. The present paper reports the progress of the research, and presents an overview of the stage-wise design process, scope and notation of the JSD* method. The method is discussed and illustrated using a simple case-study concerning a Recreation Booking System. PMID- 1516575 TI - Cognitive simulation as a tool for cognitive task analysis. AB - Cognitive simulations are runnable computer programs that represent models of human cognitive activities. We show how one cognitive simulation built as a model of some of the cognitive processes involved in dynamic fault management can be used in conjunction with small-scale empirical data on human performance to uncover the cognitive demands of a task, to identify where intention errors are likely to occur, and to point to improvements in the person-machine system. The simulation, called Cognitive Environment Simulation or CES, has been exercised on several nuclear power plant accident scenarios. Here we report one case to illustrate how a cognitive simulation tool such as CES can be used to clarify the cognitive demands of a problem-solving situation as part of a cognitive task analysis. PMID- 1516576 TI - The complex role of perceptual organization in visual display design theory. AB - Two experiments were performed to test and extend the current 'emergent features' approach to display design for dynamic failure detection tasks. It was predicted that a display whose emergent features were well-mapped to goal-relevant task invariants would lead to better failure detection performance than either of two alternative displays. Contrary to prediction. Experiment 1 showed no differences in failure detection speed or accuracy across displays. The reason for this may have been that subjects did not discover the mapping between the mathematical properties of the task and the emergent feature, so in Experiment 2 subjects were explicitly instructed about the mapping and were advised on how to use the display geometry to help their performance. A significant difference in failure detection speed emerged, but the display supporting fastest performance was not the one with the well-mapped emergent feature. These results suggest that alternative perceptual organizational factors were at work which overpowered the intended effect. The results also underscore the difficulty of developing a theory of display design, and their impact on current theories is outlined. PMID- 1516577 TI - Trust, control strategies and allocation of function in human-machine systems. AB - As automated controllers supplant human intervention in controlling complex systems, the operators' role often changes from that of an active controller to that of a supervisory controller. Acting as supervisors, operators can choose between automatic and manual control. Improperly allocating function between automatic and manual control can have negative consequences for the performance of a system. Previous research suggests that the decision to perform the job manually or automatically depends, in part, upon the trust the operators invest in the automatic controllers. This paper reports an experiment to characterize the changes in operators' trust during an interaction with a semi-automatic pasteurization plant, and investigates the relationship between changes in operators' control strategies and trust. A regression model identifies the causes of changes in trust, and a 'trust transfer function' is developed using time series analysis to describe the dynamics of trust. Based on a detailed analysis of operators' strategies in response to system faults we suggest a model for the choice between manual and automatic control, based on trust in automatic controllers and self-confidence in the ability to control the system manually. PMID- 1516578 TI - Development of microcomputer-based mental acuity tests. AB - Recent disasters have focused attention on performance problems due to the use of alcohol and controlled substances in the workplace. Environmental stressors such as thermal extremes, mixed gases, noise, motion, and vibration also have adverse effects on human performance and operator efficiency. However, the lack of a standardized, sensitive, human performance assessment battery has probably delayed the systematic study of the deleterious effects of various toxic chemicals and drugs at home and in the workplace. The collective goal of the research reported here is the development of a menu of tests embedded in a coherent package of hardware and software that may be useful in repeated-measures studies of a broad range of agents that can degrade human performance. A menu of 40 tests from the Automated Performance Test System (APTS) is described, and the series of interlocking studies supporting its development is reviewed. The APTS tests, which run on several versions of laptop portables and desktop personal computers, have been shown to be stable, reliable, and factorially rich, and to have predictive validities with holistic measures of intelligence and simulator performances. In addition, sensitivity studies have been conducted in which performance changes due to stressors, agents, and treatments were demonstrated. We believe that tests like those described here have prospective use as an adjunct to urine testing for the screening for performance loss of individuals who are granted access to workplaces and stations that impact public safety. PMID- 1516579 TI - Use of intraperitoneal chemotherapy for treatment of ovarian cancer. AB - Second line chemotherapeutic therapy following failure with Cis-platinum combined regimens for treatment of cancer of the ovary is discouraging. Similarly, results with the use of Cis-platinum combined regimens for patients with less than well debulked primary surgery are also discouraging. In an attempt to improve these results, a series of 57 patients were subjected to high dose Cis-platinum and AraC given intraperitoneally. 44 of these patients were those that had been subjected to a second look procedure after 8-12 months of Cis-platinum therapy and were found to have residual disease in the form of positive cytology or microscopic disease up to nodules of 1.5 cm in diameter. 13 of the patients, because of less than well-debulked surgical procedures, were also accepted for therapy. In all patients, a subcutaneously implanted catheter was introduced into the patient and the tube was tunneled through the subcutaneous tissue into the peritoneal cavity. Cis-platinum and AraC were introduced into the peritoneal cavity through this cutaneous line. Concurrently, with the administration of the intraperitoneal therapy, Sodium Thiosulfate was given intravenously for systemic protection from Cis-platinum toxicity. Treatments were given every three to four weeks and the number of courses varied from 3 to 8 for a total of 184 injections for the entire group. In seven of these patients distribution studies were carried out using radioactive sulfur colloids which were injected peritoneally prior to the first treatment and preceding each subsequent treatment in order to evaluate the anticipated distribution of the chemotherapeutic agents. Only 4 of the 44 patients in group 1 and 3 of the 13 patients in group 2 are alive without evidence of disease at the present time. The low success rate is believed due to the poor distribution of the chemotherapeutic agents after the first two or three injections. In most of the patients, by the third or fourth treatment, they were found to have developed loculated restricted areas with minimal distribution of the agents. This was also demonstrated by the distribution studies carried out with the sulfur colloid. PMID- 1516580 TI - Peritoneal cytology in patients with stage IB cervical cancer undergoing radical hysterectomy: limited value. AB - Peritoneal cytology, obtained at the start of planned radical hysterectomy in 200 consecutive patients with Stage IB cervical cancer, none of whom had intra abdominal extension of disease, was positive in only one patient; this patient received no adjuvant treatment and remains disease-free at 48 months. Routine peritoneal cytology during radical hysterectomy adds little information for patient management and may be safely omitted. PMID- 1516581 TI - Cisplatin in combination with continuous VP16 infusion as second line chemotherapy in ovarian carcinoma. A pilot study. AB - Effective second line chemotherapy schedules for recurrent ovarian carcinoma are not available. The combination of cisplatin and VP-16 given as a single dose in such patients gave inconsistent results. Since VP-16 is a dose-schedule dependent drug it was given in this pilot study as a continuous 72 hour infusion at a dose of 100 mg/m2/day. No objective response was observed among 7 patients with refractory or recurrent ovarian carcinoma who received a median of 3 treatment courses. PMID- 1516582 TI - Surgical treatment of vulvar cancer. AB - 59 (80%) of 74 patients with vulvar cancer treated at the University Department of Obstetrics and Gynecology in Ljubljana in the period 1973-85 underwent radical vulvectomy with bilateral inguinofemoral lymphadenectomy, and 15 (20%) patients single vulvectomy because of advanced age and poor general condition. Histologically there were 69 cases of squamous cell carcinoma, 1 adenocarcinoma, 3 malignant melanoma and 1 rhabdomyosarcoma. 52% of the patients were classified as Stage I, 41% Stage II and 7% Stage III. Positive inguinofemoral nodes were observed in 24% (6.5% in Stage I, 35% in Stage II and 80% in Stage III). The total 5 year survival rate was 70% (83% in Stage I, 61% in Stage II and 20% in Stage III). The 5 year survival rate in the patients with negative nodes was 80%, and in cases with positive nodes only 50% in spite of postoperative irradiation. None of the 3 patients with melanoma survived 2 years nor did the patient with rhabdomyosarcoma. There was no case of primary mortality. Nowadays the cure rate for vulvar cancer is higher especially owing to the improvement of operability. The problem of lymphatic and distant metastases still remains unresolved. PMID- 1516583 TI - Isolated cerebellar metastasis from ovarian carcinoma. Case report and review of the literature. AB - Isolated cerebellar metastasis from ovarian cancer is a very rare entity with only one other reported case in the literature. We report an additional case. This patient had a single 3 x 3 cm cerebellar lesion that was removed revealing metastatic papillary carcinoma consistent with a known ovarian primary. We also present a review of the literature concerning central nervous system (CNS) metastases from ovarian cancer and the various methods of treatment currently being used. Current literature suggests that patients with isolated resectable lesions should be managed surgically. PMID- 1516584 TI - Results of cyclophosphamide and cisplatin combination chemotherapy in patients with ovarian carcinoma. AB - An unselected group of 30 patients with advanced epithelial ovarian cancer, FIGO stage IIb-IV, was treated with cyclophosphamide (750 mg/m2) and cisplatin (75 mg/m2) both administered intravenously on a single day at a 3-weeks interval (CP). At a median follow-up time of 25 months this treatment had resulted in a remission rate of 73% and an estimated median overall survival time of 29 months, which resembles the results of prospective randomized trials. Major side-effects encountered in our patients were renal toxicity and neurotoxicity requiring termination of chemotherapy with CP in 9 patients. Patients with residual tumor smaller than 1 cm had a significant survival benefit as compared to patients with residual tumor greater than 1 cm. Also, patients with stage III ovarian cancer had a significant longer duration of survival than patients with stage IV disease. After a median period of chemotherapy of 7 monthly the median time without symptoms of progression and without treatment was 9 months for patients with an objective remission. We found the CP regimen to be the best therapy to hand: improvement of the prognosis might be attained by other new treatment modalities. PMID- 1516585 TI - Chromosome aberrations and expression of ras and myc oncogenes in leiomyomas and a leiomyosarcoma of the uterus. AB - Twenty eight leiomyomas and one leiomyosarcoma were cytogenetically analysed and also examined for ras and myc oncoprotein expression. Chromosome alterations were found in seven leiomyoma cases. In four of them 12q14-15 was involved. P21 product of H-ras and P62 product of c-myc genes were detected in paraffin embedded parallel tissue sections. A high expression of H-ras was apparent in most tumors. C-myc expression was weak or negative in most leiomyomas with normal karyotype while on the contrary in three out of seven cases with abnormal cytogenetic findings the gene product stained moderately positive. Considerable chromosome abnormalities and oncogene overexpression were also identified in the leiomyosarcoma. PMID- 1516586 TI - Comparison between serum CA 125 and CA 19-9 assays and tissular OC 125 and 1116NS 19-9 reactivity in malignant and benign ovarian tumors. AB - This preliminary study included 25 patients with primary epithelial ovarian cancer (EOC) (18 serous, 3 serous-mucinous, 1 endometrioid, 2 undifferentiated carcinomas and 1 malignant Brenner carcinoma); 2 patients with borderline ovarian tumors and 20 patients with benign ovarian tumors (9 benign cystic teratomas, 6 serous cystoadenomas and 5 mucinous cystoadenomas). Blood samples for the measurement of CA 125 and CA 19-9 were drawn from all patients before surgery. Serum CA 125 (Reference Value-RV = 65 U/ml) and CA 19-9 (RV = 40 U/ml) were measured with IRMAs using the monoclonal antibodies (MoAbs) OC 125 and 1116NS 19 9. The same antigens were detected on paraffin-embedded tissue sections by immunocytochemistry with the avidin-biotin complex method employing the same MoAbs used for serum IRMAs. Among the 25 patients with EOC serum CA 125 levels were elevated in 20: tissular OC 125 reactivity was observed in 15 (75%) of them. Of the 5 EOC patients with normal CA 125 levels, 4 showed OC 125 reactivity. Only 2 of the 25 EOC patients had elevated serum CA 19-9 levels: one of them had tissular 1116 NS 19-9 reactivity. Among the 23 patients with normal serum CA 19-9 levels only 5 had immunocytochemical reactivity for this antigen. The 2 patients with borderline ovarian tumors had negative serum CA 125 and CA 19-9 assay: tissular OC 125 reactivity was observed in both patients, while 1116 NS 19-9 reactivity was detected in only one.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1516587 TI - Pregnancy after in vitro fertilization in a patient with borderline tumor of the ovary. AB - A 36 year old woman with unilateral tubal disease was found, during infertility evaluation, to have epithelial tumor of borderline malignancy in one ovary. She was treated with salpingo-oophorectomy and three months later she asked to participate in our IVF program. High doses of gonadotropins were given for controlled hyperstimulation and a successful pregnancy and live birth was achieved. PMID- 1516588 TI - The diagnostic value of barium enema in cancer of the corpus uteri. AB - The diagnostic value of barium enema in staging of carcinomas of the corpus uteri was evaluated in a retrospective study of 218 patients. The primary treatment in all patients was surgical. Barium enema was performed preoperatively in 48 (22%) of the patients and postoperatively in 106 (49%); 64 (29%) of the patients were not subjected to this investigation. Barium enema revealed changes possibly due to tumor in five patients (3%): two patients exhibited stenosis of the sigmoid colon due to a stromal sarcoma (Stages III and IV), and in one patient there was evidence that the primary tumor was in fact a carcinoma of the sigmoid colon. The suspicion of bowel involvement in the two other patients (both at Stage I) proved to be unfounded. These results show that barium enema is unnecessary in carcinoma of the corpus uteri at Stages I and II, and that in Stages III and IV the necessity for this investigation should be considered for each patient on an individual basis. PMID- 1516589 TI - Value of CA 125 as a marker of ovarian cancer. AB - Elevated CA 125 level was noted in 0.2-5.9% healthy women, 2.2-27.8% patients with benign ovarian cysts, and approximately 80% patients with nonmucinous ovarian cancer. In the early stages of cancer, CA 125 level was lower than in the disseminated process (with tendency to higher levels in cases of accompanying exudates to body cavities). The level was found to correlate with the mass of tumor, extent of surgery and response to chemotherapy. Maintenance or increase in CA 125 level after three months of chemotherapy was found to indicate ineffectiveness of the treatment, suggesting a more aggressive therapeutic strategy. The estimation of CA 125 half life after the first two courses of chemotherapy was noted to be a good prognostic factor (9.2 to 10.73 days in patients with total remission, and 22.6 to 44.87 days in patients with progression). The monitoring of ovarian cancer courses using CA 125 level estimations in the serum facilitated decisions at to the timing of the second look operation; elevated level of the marker was found to indicate that the latter was superfluous. Elevated CA 125 level proceeded clinical diagnosis of relapse by 3 to 6 months, but only in the patients who at earlier stages of the treatment also showed abnormal levels of the marker. The monitoring of patients with complete remission who showed normal CA 125 level throughout the treatment was found useless. PMID- 1516590 TI - Is cholesterol reduction always safe? PMID- 1516591 TI - Cell adhesion/signalling: biology and clinical applications. PMID- 1516592 TI - Bone mineral density measured by dual-energy X-ray absorptiometry in normal men. AB - A cross-sectional study of 222 healthy Finnish men aged 20-69 years was performed to establish reference values of bone mineral density (BMD) using dual-energy X ray absorptiometry (DEXA). The effects of age, and of some physical and lifestyle factors on BMD of the lumbar spine and proximal femur (femoral neck, Ward's triangle and trochanter) were investigated. The maximal mean BMD was observed at the age of 20-29 years in all the measurement sites. Except for the trochanteric area, BMD diminished along with age, the over-all decrements being 4%, 11%, and 23% in the lumbar, femoral neck and Ward's triangle areas, respectively. BMD was in a positive relationship to weight and height in all the measurement sites. The adjusted (for age, height and weight) BMDs were higher (P less than 0.05) in the group of daily dietary calcium intake greater than 1200 mg as compared with the group of lowest calcium intake (less than 800 mg day-1) in the three femoral areas. Cigarette smoking or alcohol drinking had no obvious effect on BMD. PMID- 1516593 TI - Human macrophages modulate the phenotype of cultured rabbit aortic smooth muscle cells through secretion of platelet-derived growth factor. AB - Phenotypic change of aortic smooth muscle cells (SMC) is a key step for their abnormal proliferation in atheromatous lesions. In this study modulation of the growth properties of SMC by macrophages was investigated to clarify the mechanism regulating the SMC phenotype. Cultured rabbit SMC preincubated with either macrophages derived from human peripheral monocytes, or conditioned medium from macrophages grew faster than control SMC in the absence of either macrophages or conditioned medium. SMC preincubated with purified platelet-derived growth factor (PDGF) also grew faster than control SMC in the absence of PDGF, and their rapid growth was maintained for at least two passages. SMC preincubated with conditioned medium of macrophages plus anti-PDGF antibody did not grow faster than control SMC. Furthermore SMC preincubated with PDGF acquired the ability to secrete some mitogen, which differed from PDGF. These results suggest that macrophages modulate the phenotype of SMC by a mechanism mediated by PDGF. As a result the SMC grow faster and at the same time secrete some mitogen probably distinct from PDGF in an autocrine manner. PMID- 1516594 TI - Evidence that human kidney produces a protein similar to lithostathine, the pancreatic inhibitor of CaCO3 crystal growth. AB - Pancreatic juice is supersaturated in calcium carbonate. CaCO3 crystal growth is controlled by lithostathine, a secretory protein synthesized by pancreatic acinar cells, first described as a constituent of pancreatic stones. It was recently reported that, in the thin descending limb of the Henle's loop, urine was supersaturated in CaCO3 (Coe FL, Parks JH: Defenses of an unstable compromise: crystallization inhibitors and the kidney's role in mineral regulation. Kidney Int. 1990: 38, 625-631. This observation suggested the presence in kidney of a similar inhibitor. In this study, we show that a protein immunologically related to lithostathine is actually present in urine of healthy subjects and in renal stones. Immunocytochemistry of kidney sections localized the protein to cells of the proximal tubules and thick ascending limbs of the Henle's loops. Protein extracts of renal stones inhibited CaCO3 crystal growth in vitro and this inhibition was significantly lifted by incubating the extracts with antibodies to lithostathine. The protein is not immunologically related to nephrocalcin. Because of its structural and functional similarities with pancreatic lithostathine, it was called renal lithostathine. PMID- 1516595 TI - Inheritance of monoclonal rheumatoid factor cross-reactive idiotypes in primary Sjogren's syndrome (pSS). Comparative studies of a rabbit polyclonal anti idiotype and 17109 monoclonal anti-idiotype. AB - A comparison of the presence of two idiotypes, one identified by a rabbit polyclonal antiidiotypic antibody, first found on a cryoprecipitable IgM chi rheumatoid factor (RF) from an SS patient (3rd SS) and the 17109 idiotype, identified by a monoclonal antibody was performed in 106 sera and eight minor salivary gland biopsies of Sjogren's syndrome (SS) patients and 125 sera from age sex matched normal controls. Of 106 of SS patients' sera 36 had immunoglobulins positive for the 3rd SS idiotype. 17109 activity was more prevalent in SS patients positive for the polyclonal anti-idiotype 3rd SS, than those with negative idiotype (9/36 VS 2/70 chi 2 = 12.53 P less than 0.005). Cross inhibition studies, however, revealed that the polyclonal anti-idiotype binding was not inhibited by the 17109 moAb. 3rd SS and 17109 anti-idiotypes were reacted with immunoglobulins in the serum of 3.5% and 1.7% of normal human sera respectively. Immunohistologic studies demonstrated that 4/8 and 2/6 minor salivary gland biopsies had infiltrating plasma cells containing immunoglobulins bearing the 3rd SS and the 17109 idiotypes, respectively. The inheritance of both idiotypes was investigated in sera of 4 SS kindreds. In two kindreds with 3rd SS positive probands, the idiotype was detected in 3 first degree relatives of the same generation. 17109 activity was detected in the serum of a sister of the positive proband who had a high RF titer. These results suggest that the 17109 moAb recognizes a different epitope of that of the 3rd SS. The idiotypes of monoclonal RFs are not inherited and probably are produced by plasma cells infiltrating the labial minor salivary glands of SS patients. PMID- 1516596 TI - Patients with anticardiolipin antibodies with and without antiphospholipid syndrome: their clinical features and beta 2-glycoprotein-I plasma levels. AB - The clinical and serological features of 38 aCL-positive patients were compared to those of 45 aCL-negative patients. A significantly higher incidence of thrombophlebitis and livedo reticularis was found in aCL-positive patients. There were 13 aCL positive patients with thrombophlebitis and/or arterial thromboses and these 13 patients were designated as having the antiphospholipid syndrome (APS) while the remaining 70 patients were diagnosed as having Systemic Lupus Erythematosus (SLE). APS patients also had a high incidence of arterial occlusions, recurrent abortions and strokes compared to SLE patients. Patients with high levels of IgG-aCL were more likely to have APS, while patients with low levels of IgG-aCL or IgM-aCL only were more likely to have SLE without the clinical features of APS. Since aCL antibodies have recently been shown to interact with a phospholipid-binding plasma protein beta 2-glycoprotein-I (beta 2 GPI), we measured the beta 2-GPI levels in these patients and found that beta 2 GPI levels are significantly higher in APS compared to SLE patients negative for aCL antibodies. Since beta 2-GPI is known to exert multiple effects on coagulation processes the interaction of aCL antibodies with this glycoprotein may play a pathogenic role in APS. PMID- 1516597 TI - Tumor necrosis factor alpha is associated with disease activity and the degree of anemia in patients with rheumatoid arthritis. AB - To elucidate the role of tumor necrosis factor alpha (TNF) in determining anemia of chronic disease (ACD) in rheumatoid arthritis (RA), 24 patients were studied for disease parameters, TNF serum levels and bone marrow for erythroid colony growth and compared with six controls. Serum TNF alpha was highest in ACD and correlated well with RA disease parameters. Both TNF and other RA disease parameters correlated inversely with degree of anemia. BFUe counts were lower in ACD, correlated positively with Hb and negatively with erythrocyte sedimentation rate (ESR). TNF reduced whereas anti-TNF upregulated in vitro erythroid colony counts. TNF production occurred in similar amounts in bone marrow cultures in the three groups. From these preliminary findings we conclude that ACD in RA correlates with by RA disease activity and that TNF may serve not only as an RA disease marker but also could be one of the factors mediating impaired erythropoiesis in ACD in active RA. PMID- 1516598 TI - Effect of a somatostatin analogue, octreotide, on renal haemodynamics and albuminuria in acromegalic patients. AB - Although insulin-like growth factor I increases renal function, the renal haemodynamic abnormality underlying the glomerular hyperfiltration in acromegaly is unknown. In normal subjects, amino acids and low doses of dopamine increase the glomerular filtration rate (GFR) and effective renal plasma flow (ERPF), presumably by a predominant vasodilation of the afferent and efferent glomerular arterioles, respectively. We studied baseline GFR and ERPF (determined with 125I iothalamate and 131I-hippuran, respectively), the renal stimulatory effects of amino acid and dopamine infusion, and albuminuria before and after 3 months octreotide treatment in seven acromegalic patients with metabolically active disease. Octreotide reduced growth hormone concentrations from 14.7 +/- 3.0 to 5.5 +/- 1.0 micrograms l-1 (mean +/- SEM, n = 7; P less than 0.001) and insulin like growth factor I levels from 4.12 +/- 1.31 to 2.44 +/- 0.68 kU l-1 (P less than 0.02). Glucagon concentrations did not change. Baseline GFR and ERPF declined from 132 +/- 5 to 117 +/- 6 and from 547 +/- 32 to 478 +/- 31 ml min-1 1.73 m-2, respectively (P less than 0.05 for both). Initially the response to amino acids was impaired (increment in GFR: 4.8 +/- 6.0%, NS; ERPF: -1.5 +/- 6.8%, NS), whereas the response to dopamine was normal (GFR: 10.6 +/- 1.1%, P less than 0.05: ERPF: 33.2 +/- 3.1%, P less than 0.01). After octreotide, amino acid infusion increased GFR by 15.0 +/- 6.8% (P less than 0.02) and ERPF by 11.3 +/- 5.6% (P less than 0.02), while the dopamine response was unchanged.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1516599 TI - Short- and long-term effects of lovastatin and pravastatin alone and in combination with cholestyramine on serum lipids, lipoproteins and apolipoproteins in primary hypercholesterolaemia. AB - The effects of the HMG CoA reductase inhibitors lovastatin and pravastatin on serum lipids, lipoproteins and apolipoproteins have been studied in 35 patients with primary hypercholesterolaemia. LDL cholesterol was lowered to the same extent by both agents compared on a mg basis of each drug per day. HDL cholesterol was increased by lovastatin but not by pravastatin. The reduction in serum triglycerides, VLDL triglycerides and VLDL cholesterol was more pronounced after lovastatin than pravastatin. After 1 year the effect of combined treatment with 40 mg pravastatin and 8 g cholestyramine on the reduction in LDL cholesterol (-39%) in 13 patients was comparable to that of 80 mg lovastatin plus 8 g cholestyramine (-40%) in 12 patients with identical baseline values. Differences were also found in the effects of the combination therapy with the two drugs on HDL cholesterol, serum triglycerides, VLDL triglycerides, VLDL cholesterol, and apolipoproteins. PMID- 1516600 TI - Influence of food on serum ambenonium concentration in patients with myasthenia gravis. AB - Influence of food on the serum concentration and kinetics ambenonium chloride (AMBC) has been examined in thirteen patients with myasthenia gravis (MG). Mean serum concentrations and Cmax during fasting were higher than those in the non fasting state. The AUC (0-3 h) was also about four-times larger. The drug effects versus the serum concentration were observed to be anti-clockwise or clockwise. The effective range of the Cmax varied between patients. The unexpected increase in Cmax led to adverse muscarinic actions of AMBC, when the condition was changed from the nonfasting to the fasting state. It is recommended that the dose be changed during non-fasting treatment when adjusting the optimum regimen for patients myasthenia gravis. Patients must be advised to keep to the dosing and dietary schedule in order to avoid unexpected adverse actions to AMBC. PMID- 1516601 TI - The effects of dopamine and a low protein diet on glomerular filtration rate and renal plasma flow in the aged kidney. AB - The aims of this study were to determine the effects of dopamine and a low protein diet on glomerular filtration rate and effective renal plasma flow in the aged kidney. Effective renal plasma flow was measured using 125I-labelled hippuran and glomerular filtration rate using 51Cr-labelled EDTA. Low-dose continuous intravenous dopamine 3 micrograms.kg-1.min-1 in 10 healthy elderly volunteers caused a significant increase in effective renal plasma flow but not in the mean glomerular filtration rate when compared with baseline. However, glomerular filtration rate did increase substantially in 5 subjects (mean 14.4, SD 1.3). This implied that the elderly kidney was working maximally without reserve capacity in half the elderly. Since renal function is likely to be even more reduced in elderly patients with congestive cardiac failure, dopamine infusions may have little place in this condition in some older patients. A low protein diet (0.69 g.kg-1) in the same volunteers reduced glomerular filtration rate, suggesting that protein restriction may help to reduce the increased filtration rate in the remaining nephrons, thereby leading to structural and functional preservation in the aged kidney. PMID- 1516602 TI - Effect of oral defibrotide on tissue-plasminogen activator and tissue-plasminogen activator inhibitor balance. AB - Defibrotide, a polydeoxyribonucleotide of mammalian origin, has been shown to reduce the blood level of the plasminogen activator inhibitor, and so to increase the activity of tissue plasminogen activator without any adverse effect. A randomized, double-blind, placebo-controlled study has been done in 22 patients, 14 with peripheral vascular disease, 6 with coronary heart disease and 2 with cerebrovascular disease. Patients were given defibrotide 400 mg b.d. or identical placebo for 30 days and the parameters of fibrinolysis were evaluated before and after the treatment. A significant increase in tissue plasminogen activator activity at rest and after venostasis was observed after defibrotide; tissue plasminogen activator antigen at rest and after venostasis was not affected by either treatment. Defibrotide significantly reduced plasminogen activator inhibitor activity and antigen at rest. Only one patient complained of gastric pain after placebo treatment. The study shows that defibrotide has profibrinolytic property and that it could be used to explore the role of plasminogen activator inhibitor in venous and arterial thrombosis. PMID- 1516603 TI - Adverse events in phase one studies: a study in 430 healthy volunteers. AB - All the clinical, laboratory and electrocardiographic adverse events detected during 24 Phase I studies in the same unit over a 5 y period are reported here. 430 healthy male volunteers were involved, corresponding to 5488 days of follow up. The overall incidence of adverse events was 13.5%, with a significant difference between active drug (15.3%) and placebo (7.4%) treatments. There were 69 distinct types of adverse events. Headache was the most frequent symptom (2%). There were severe adverse events in 20 cases (0.36%), with an incidence of 20/430 per subject (4.6%). There were no deaths or life-threatening events. Although the main objective of Phase I studies is to determine the maximum dose tolerated, cause-effect relationships with adverse events are hard to establish, because of the frequency of adverse events with placebo, and because of the limited number of subjects included such studies. PMID- 1516604 TI - FARMAGUIDA: a databank for the analysis of the Italian drug market and drug utilization in general practice. AB - FARMAGUIDA, a databank of drugs marketed in Italy (2,596 pharmaceutical substances corresponding to 10,448 products), permits analysis of the nature and value of the drugs prescribed. It contains coded pharmaceutical and administrative information, an original classification, as well as indicators of the therapeutic status of each drug. The FARMAGUIDA classification was built hierarchically according to a three-level pattern: the first level (42 categories) corresponds to major pharmacological groups; the second level (157 groups) gathers drugs having similar clinical indications and/or pharmacological actions; and the third level (246 subgroups) classifies drugs according to chemical structure and/or the mechanism of action. Drugs not falling into well established pharmacotherapeutic criteria (e.g. neurotropics or liver protectants) are classified into separate subgroups. Two larger groupings were also formulated: THER (11 headings), a utilization-oriented arrangement in which each heading also contained the corresponding placebo-like drugs, and PHARM (14 headings), a rational pharmacological arrangement, in which all placebo-like drugs were relegated into a separate set. The following quality indicators were created: DOC, which defines five degrees of documentation of clinical efficacy according to major textbooks of pharmacology and therapeutics; CLASS, which groups DOC values for a more simple evaluation of prescription data; PREP, which distinguishes monocomponent preparations from fixed-dose combinations, and also provides coded information about the rationale for the combination; HOSP, which hallmarks drugs that should be reserved for in-patients, e.g. anti-pseudomonal antibiotics. The composition of the list of reimbursable drugs, the Italian National Formulary (NF; 5782 products in 1990) was analyzed according to the FARMAGUIDA classification and indicators.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1516605 TI - Drug utilization in general practice: prescribing habits of National Formulary drugs by GPs of Emilia Romagna (Italy) in 1988 and 1989. AB - Two years of prescriptions for all the drugs included in the Italian National Formulary by 3,866 general practitioners, in a region of Northern Italy of almost 4 million inhabitants, were analysed to determine the pattern of drug use. The data (official code and proprietary name of the drug, number of packages prescribed, price of the drug, dispensing pharmacy, and date of dispensing) were collected monthly by retail pharmacies and were recorded and organized in database files. Quantitative and qualitative profiles of prescription patterns were studied for all the major therapeutic areas. Overall drug prescriptions averaged 600 DDD/1,000 inhabitants/day. Comparison of 1988 and 1989 data showed only a slight increase in total drug prescriptions, but greater changes were detected in certain drug groups, especially those recently marketed. Overprescription of well-documented drugs, such as H2-antagonists, ACE inhibitors, calcium antagonists and the HMG-CoA-reductase inhibitors, in comparison to other countries was shown. There was frequent prescribing of drugs devoid of documentation of their clinical efficacy, which were mainly given for clinical conditions lacking a specific treatment, or as placebos for minor disorders. The data demonstrate the need for educational intervention to improve the quality of drug prescribing habits in primary health care in Italy. PMID- 1516606 TI - The influence of levodopa on gastric emptying in healthy elderly volunteers. AB - Paracetamol absorption and 99Tc-DTPA measurements have been used to determine the influence of levodopa on gastric emptying in 8 healthy elderly volunteers. In the absence of levodopa 7 subjects showed a rapid gastric emptying pattern by gamma camera and a single major peak in the plasma concentration-time curve of paracetamol. One subject showed two rapid phases of gastric emptying separated by a period of negligible emptying and had 2 separate peaks in the paracetamol plasma concentration-time curve. In the presence of levodopa, the gamma-camera data for 6 subjects showed a pattern of gastric emptying consisting of 2 rapid phases separated by a plateau. In each case secondary peaks in the plasma concentration-time curve of paracetamol occurred about 30 min after the end of the plateau. The time to 90% emptying on the gamma scan was increased significantly from 40 min to 65 min in the presence of levodopa. Comparison of the present data with those reported previously indicates that levodopa affects gastric emptying in the both elderly and young volunteers to a similar extent. PMID- 1516607 TI - Stereoselective pharmacokinetics of oral nitrendipine in elderly hypertensive patients with normal and impaired renal function. AB - The pharmacokinetics of the enantiomers of nitrendipine has been studied in seven elderly patients with chronic renal failure (CRF) and in six control subjects (mean creatinine clearance 30 and 97 ml.min-1 respectively). Racemic nitrendipine 20 mg was given once daily for seven days and the pharmacokinetics of the enantiomers over the last dosage interval were determined using a stereospecific assay. In both groups nitrendipine exhibited stereoselective pharmacokinetics (AUC, Cmax), but the half-lives of the enantiomers did not differ in individual subjects. As an index of stereoselectivity, the mean S/R ratio of AUCs in control subjects (2.07) was not significantly different from the ratio in patients with CRF (2.68). The mean AUCs of (S)- and (R)-nitrendipine during the last dosage interval were increased in CRF by 132% and 85%, respectively. The observed doubling of the half-lives and the increases in Cmax did not reach significance because of the large variability in each group. Thus, the pharmacokinetics of oral nitrendipine is altered in CRF, but there was no change in the stereoselectivity of its pharmacokinetics. PMID- 1516608 TI - Kinetics of action of salbutamol inhaled from a metered dose inhaler (MDI) and a "Diskhaler". AB - In a double-blind cross-over study, 12 patients with reversible airways obstruction were treated with 200 micrograms salbutamol base in aerosol or 400 micrograms of powder following methacholine-induced bronchoconstriction. Salbutamol was inhaled either from a conventional metered dose inhaler (MDI) or from an inhaler (Diskhaler) utilizing the powdered form of the drug. The efficacy of both forms was identical whether assessed in terms of FEV1 or vital capacity. The ratio of the increase in FEV1 or vital capacity after bronchodilatation to the decrease during the prior bronchoconstriction was 1.4, indicating that both FEV1 and vital capacity improved over baseline following bronchodilatation. In six subjects, the onset of action of the powder form was more rapid, and in four the MDI acted more rapidly. In the group as a whole, the mean time constant for the action of salbutamol was identical (3.8 min) for the two forms. It is concluded that salbutamol powder has a similar efficacy and time course of action as the aerosol, probably because both formulations produce similar sized particles of the drug. PMID- 1516609 TI - The pharmacokinetics and pharmacodynamics of sublingual and oral alprazolam in the post-prandial state. AB - We gave 12 healthy male volunteers 1 mg of alprazolam or placebo on three occasions after a standard breakfast in a double-blind, randomized, single-dose, three-way crossover study. The three trials were: (a) oral alprazolam and sublingual placebo; (b) oral placebo and sublingual alprazolam; (c) placebo by both routes. Plasma alprazolam concentrations during 24 h after each dose were measured by electron-capture gas-liquid chromatography. Peak plasma concentrations were reached later after sublingual than oral dosage (2.8 vs 1.8 h, P less than 0.01). Other kinetic variables were not significantly different: peak plasma concentration, 11.3 vs 12.0 ng.ml-1; elimination half-life, 12.5 vs 11.7 h; and total area under the plasma concentration versus time curve, 197 vs 186 h.ng.ml-1. Pharmacodynamic measures showed that sublingual and oral alprazolam both produced sedation, fatigue, impaired digit symbol substitution, slowing of reaction time, and impairment of the acquisition and recall of information. These changes were initially observed at 0.5 h after dosage and lasted up to 8 h. In general the two routes were significantly different from placebo but not from each other. PMID- 1516610 TI - Pharmacokinetics of ethanol in plasma and whole blood: estimation of total body water by the dilution principle. AB - The pharmacokinetics of ethanol in plasma and whole blood have been investigated and the results used to estimate the volume of total body water (TBW) by means of the dilution principle. Fifteen men (mean age 62 y) were given 0.6 g ethanol/kg body weight as an intravenous infusion over 1 h. The peak concentration of ethanol in plasma was 120 mg.dl-1 compared to 108 mg.dl-1 for whole blood. The disappearance rate of ethanol from plasma was 18.6 mg.dl-1.h-1 compared to 17.0 mg.dl-1.h-1 for the whole blood concentration-time data. The apparent volume of distribution of ethanol (Vz) was 0.54 l.kg-1 according to plasma kinetics compared to 0.59 l.kg-1 for the kinetics derived from whole blood. The mean area under the curve (AUC) was 294 mg.dl-1 x h for plasma kinetics compared to 266 mg.dl-1 x h for whole blood. The TBW was 40.9 l or 50.9% of body weight for the plasma concentration-time data. This agreed well with the 40.3 l or 50.1% of body weight obtained using whole blood. PMID- 1516611 TI - Inhibition by basic drugs of digoxin secretion into human bile. AB - Bile samples from previous interaction studies in man were re-analysed by a combined HPLC/radioimmunoassay method. Quinidine, quinine and verapamil but not probenecid or spironolactone were found to inhibit the biliary secretion of unchanged digoxin. PMID- 1516612 TI - Verapamil and drug metabolism by the cytochrome P450 isoform CYP1A2. PMID- 1516613 TI - Active lymphocyte traffic induced in the periphery by cytokines and phytohemagglutinin: three different mechanisms? AB - Phytohemagglutinin (PHA) injection induces transient protease-sensitive traffic of lymphocytes in skin and other tissues in several species. Examination of the possible roles of cytokines in such reactions showed that recombinant bovine and human tumor necrosis factor (TNF)-alpha potently induce dose-dependent lymphocyte traffic in pig skin (and in other tissues including the draining lymph nodes) with early kinetics and a morphology of the inflammatory reaction similar to that of PHA (peaking 9-12 h). Recombinant human interleukin (IL)-1 alpha also induces dose-dependent lymphocyte traffic, but it peaks at 4 h. Entry of labeled lymphocytes into inflammatory sites induced by PHA, TNF-alpha and IL-1 alpha, but not into normal skin, is inhibited by approximately 80% by their pretreatment with trypsin, indicative of the induction of endothelial determinants recognized by protease-sensitive surface molecules on the lymphocytes. Even the minimal lymphocyte traffic induced by interferon-gamma and lipopolysaccharide was similarly protease sensitive. At the earliest stage (approximately 2 h) of significant induction of lymphocyte entry by TNF-alpha and IL-1 alpha the inductive signal for each appears easily saturated. Thus lymphocyte entry is little increased by increasing low cytokine doses over 100-fold: However, these reactions are additive, and this was used to confirm that they are distinct from each other and from PHA. A further distinction was revealed by the homing of lymphocytes pretreated with pertussis toxin: such lymphocytes were greater than 90% inhibited in their homing to tissues through constitutive high endothelial venules (HEV) and greater than 60% inhibited in homing to TNF-alpha and IL-1 alpha skin sites, but unaffected in homing to PHA skin sites (like most non-HEV mediated traffic). Moreover, potent chicken anti-TNF-alpha, which prevented TNF induced lymphocyte entry, did not affect PHA-induced traffic. Thus, these three agents which induce peripheral lymphocyte traffic appear to involve different mechanisms as shown by differences in (i) their kinetics; (ii) the effect of anti TNF-alpha and (iii) the effect of pertussis toxin treatment of the lymphocytes and by the fact that their inductive mechanisms are additive in effect. PMID- 1516614 TI - Random entry of circulating lymphocyte subsets into peripheral lymph nodes and Peyer's patches: no evidence in vivo of a tissue-specific migration of B and T lymphocytes at the level of high endothelial venules. AB - Lymphocytes continuously migrate through the body and thus immune competent cells are constantly delivered to most tissues. They interact with high endothelial venules (HEV) via specific homing receptors and vascular addressins, and these molecules seem to be the reason for a preferential homing of B lymphocytes into Peyer's patches and of T lymphocytes into peripheral lymph nodes. When lymphocytes derived from lymph node cell suspensions were applied in the in vitro lymphocyte/endothelium binding assay, the well-known preference of mouse lymph node B lymphocytes for Peyer's patch HEV compared to peripheral lymph node HEV was confirmed in the rat (2.8 times). When in the same in vitro assay thoracic duct lymphocytes (TDL) were used this preference was far less obvious (1.4 times). However, by injecting rat TDL intravenously and by tracing them directly in HEV, B, T, CD4+ and CD8+ lymphocytes are seen to enter Peyer's patches and peripheral lymph nodes in vivo without preference. Thus, in contrast to lymphocytes from lymph node cell suspensions, no evidence was found of a tissue specific migration of thoracic duct B, T, CD4+ and CD8+ lymphocytes at the HEV level. This finding demonstrates the importance of considering both experimental conditions and the cell source used when investigating lymphocyte traffic. PMID- 1516615 TI - Preferential usage of JH2 in D-J joinings with DQ52 is determined by the primary DNA sequence and is largely dependent on recombination signal sequences. AB - Rearrangement of DQ52 with JH in IgH genes takes place in a large part of lymphocytes at a very early stage of differentiation although usage of DQ52 seems to be limited in the functional IgH genes of mature B cells. A possible and likely explanation for this, is secondary D-JH joinings occurring after the initial DQ52-JH joinings, which becomes possible only when DQ52 segments join 5' located JH segments. Previously we reported the non-random use of JH in joinings with DQ52, in which DQ52-JH2 joinings are dominant. We questioned how the preferential usage of JH2 in DQ52-JH joinings is determined by utilizing extrachromosomal DNA substrates. Extrachromosomal DNA substrates with a combination of DQ52 and multiple JH segments were prepared. These plasmids with a polyoma-derived replication system were transfected into pre-B cell lines and recombination profiles of recovered plasmids were analyzed semi-quantitatively. Experiments with plasmids containing all four JH segments in normal configuration showed an apparent high frequency of JH2 usage, similar to the rearrangement previously observed in thymocyte genomes. In plasmids containing two JH segments, when one was JH2, it was rearranged more frequently than the other, independent of its proximity to DQ52. The JH3 with recombination signal sequences (RSS) substituted for JH2 was rearranged more frequently than the naive JH2 itself indicating the importance of RSS. A JH3 hybrid with the 200 bp upstream sequence of JH2 but excluding RSS, however, failed to increase JH3 use. The addition of one nucleotide to the 22-bp spacer of JH1 RSS increased the frequency of JH1 usage. These observations suggest that the preferential usage of JH2 is determined by the primary DNA sequence and is largely dependent on RSS. PMID- 1516616 TI - Human monoclonal striational autoantibodies isolated from thymic B lymphocytes of patients with myasthenia gravis use VH and VL gene segments associated with the autoimmune repertoire. AB - The production of autoantibodies reactive with components of skeletal muscle is characteristic of myasthenia gravis (MG) and is strongly associated with the presence of thymic epithelial tumors in patients with MG. The nucleotide sequences of the heavy and light chain variable regions (VH and VL) of three human monoclonal striated muscle antibodies (StrAb) isolated from thymic B lymphocyte lines from two patients with MG and thymoma were analyzed. The VH and VL gene segments used by these anti-striated muscle antibodies appear to be derived from the same repertoire of gene segments as have been found in other autoantibodies isolated from patients with a number of different autoimmune diseases. While the IgM StrAb SA-1A is a direct copy of germ-line VH and VL gene segments, analysis of the IgG StrAb SA-4A and SA-4B, which may be more representative of antibodies found in the serum of MG patients, suggests that the processes of antigenic selection and somatic mutation may contribute to the generation of autoantibodies in MG. PMID- 1516617 TI - Association of the human invariant chain with H-2 Db class I molecules. AB - We describe two proteins of 24 kDa and 33 kDa (p24 and p33) which associate with H-2 Kb and H-2 Db molecules, respectively, in human cells transfected with H-2 Kb and H-2 Db genes. This association is particularly clear in the mutant cell line T2, in which association of endogenous peptide with newly synthesized class I molecules may not occur (V. Cerundolo et al., Nature 1990. 345: 449). We show that p33 is the 33-kDa form of the human invariant chain which is resident in the endoplasmic reticulum of T2 cells (P. Cresswell, Cold Spring Harbor Symp. Quant. Biol. 1989. LIV:309). The stability of the invariant chain H-2 Db complex is critically dependent upon occupation of the class I binding site by peptide ligand. In the absence of peptide, the complex is stable at 4 degrees C whereas following exposure to peptide, the invariant chain dissociates rapidly from H-2 Db molecules (half-life of 30 min at 4 degrees C). Although the interaction between the human invariant chain and murine H-2 Db is unlikely to have any functional significance, the peptide-induced dissociation of the invariant chain is consistent with a conformational change in H-2 Db on peptide binding. PMID- 1516618 TI - Immunosuppression induced by nitric oxide and its inhibition by interleukin-4. AB - Mice immunized with attenuated Salmonella typhimurium, strain SL3235, while protected against virulent challenge, are unable to mount in vivo and in vitro antibody responses to non-Salmonella antigens, such as tetanus toxoid and sheep red blood cells, and exhibit profoundly suppressed responses to B and T cell mitogens. Suppression of antibody responses is mediated by macrophage (M phi) released soluble factors, and is completely reversed by treatment with interleukin (IL)-4. The present report identifies the suppressor factor as nitric oxide (NO), and provides evidence for a mechanism by which IL-4 abrogates suppression. Suppressed antibody responses correlated with high levels of NO secretion by splenocytes of SL3235-immunized mice. NO production was observed only in cultures consisting of the adherent cell fraction of immune splenocytes. Further, immunosuppression was reversed by NG-monomethyl-L-arginine (NMLA), a competitive inhibitor of NO synthesis, and was completely blocked by the addition of excess L-arginine. Treatment with IL-4, or anti-interferon (IFN)-gamma monoclonal antibody (mAb), also abrogated suppression. Optimal reversal of suppression was observed only when NMLA, IL-4, or anti-IFN-gamma mAb, was added at day 0 of the 5-day plaque-forming cell assay. Treatment with either IL-4 or anti-IFN-gamma mAb also lead to a sharp inhibition of NO production by immune spleen cells. Moreover, the addition of IL-4 to splenic adherent M phi inhibited their ability to generate NO. Our data characterize an immunoregulatory pathway, involving IFN-gamma and NO, by which M phi mediate immunosuppression and identify IL-4 as a potent inhibitor of this pathway. PMID- 1516619 TI - Cytokines inhibit the development of liver schizonts of the malaria parasite Plasmodium berghei in vivo. AB - The effect of induction of an acute-phase response and its mediators on the development of liver schizonts of the rodent malaria parasite Plasmodium berghei was investigated in Brown Norway rats. Subcutaneous injection of turpentine oil 24 h or 5 min before inoculation of sporozoites resulted in 80% and 35% reduction of schizont development, respectively. Turpentine oil induced high plasma levels of interleukin-6 (IL-6). Intraperitoneal administration of IL-1, IL-6 or both, significantly reduced liver schizont development. This reduction was also present if IL-6 had been administered 24 h after sporozoite inoculation. Inhibition induced by IL-1 could be prevented by simultaneous administration of polyclonal anti-IL-6. Administration of polyclonal anti-IL-6 without IL-1 resulted in a 40% increase of liver schizonts compared to control animals. We conclude that induction of an acute-phase response during experimental Plasmodium berghei infections in Brown Norway rats, strongly inhibits liver schizont development and that IL-6 is a key mediator in this process. PMID- 1516620 TI - Tyrosine kinase triggering in thymocytes undergoing positive selection. AB - Developing T cells undergo distinct selection processes that determine the T cell receptor (TcR) repertoire. One of these processes is positive selection. Positive selection involves the differentiation to mature T cells of thymocytes bearing TcR capable of recognizing antigens in the context of self-major histocompatibility complex (MHC) molecules. To study the potential involvement of tyrosine phosphorylation in the mechanism of positive selection, we have analyzed the activities of the tyrosine kinases pp56lck and pp59fyn in thymocytes expressing a unique TcR specific for HY antigen+ H-2 Db. Thymocytes undergoing positive selection displayed higher kinase specific activities of pp56lck and pp59fyn than nonselecting thymocytes. Furthermore, these increases in kinase activities were found only in the CD4+CD8+ subpopulation of thymocytes, where the selection process is believed to occur. These data suggest that tyrosine phosphorylation is part of the intracellular signals involved in MHC class I driven positive selection from CD4+CD8+ immature thymocytes to CD4-CD8+ mature cells. PMID- 1516621 TI - Kinetics of cytokine mRNA production in the brains of mice with progressive toxoplasmic encephalitis. AB - C57BL/10 ScSn (B10) mice infected orally with Toxoplasma gondii were killed on days 5, 10, 15, 20 and 30 post infection and their brains excised. These were either used to count total tissue cyst numbers or divided for RNA purification and histopathological studies. The first signs of inflammation were on day 10 post infection, before the appearance of cysts in the brain, and correlating with the appearance of activated astrocytes. These mice had a mild meningitis with areas of encephalitis. Small numbers of cyst stages were first observed in the brain on day 15 and by day 20 the cyst numbers had increased dramatically but were not always associated with inflammation. After this time point, total cyst numbers did not increase significantly though there developed a marked variation in tissue cyst size with larger cysts becoming more numerous. The use of the polymerase chain reaction to assist in the amplification of brain RNA allowed the characterization of the kinetics of cytokine production within the brains of these animals. Only IL-1 alpha was found to be expressed constitutively in control mice. Transcripts for other cytokines associated with activated monocytes, microglial cells and astrocytes [tumor necrosis factor (TNF)-alpha and interleukin (IL)-6] were present on day 10, (IL-6) and day 15 (TNF-alpha) post infection. Thereafter, these cytokines were present in all infected animals. Of the T cell-associated cytokines, IL-4, a characteristic product of the T helper (Th)2 cell subset, was detected on days 10 and 15, while granulocyte macrophage colony stimulating factor (GM-CSF) which can be produced not only by this cell type but also by Th1 cells and CD8+ T cells, was also present on day 15 but not thereafter. Transcripts for interferon (IFN)-gamma, present from day 15 post infection, were probably produced by CD8+ T cells, as IL-2 which would indicate Th1 cell involvement was only detected 30 days after infection. The continual presence of IFN-gamma and TNF-alpha, cytokines with reported anti-toxoplasmic activity, in the CNS of B10 mice throughout the latter half of the experimental period did not diminish the severity of infection. These results indicate that the CD4+ Th2 subset may allow a rapid rise in cyst numbers and so be important in determining susceptibility to toxoplasmic encephalitis. PMID- 1516622 TI - The induction of resting B cell differentiation does not require T cell contact. AB - A T cell clone as well as immediately ex vivo CD4+ lymph node T cells are shown to support the differentiation of co-cultured resting B cells in the absence of T cell-B cell contact. Antibodies specific for class II products of the major histocompatibility complex inhibit the transactivation of resting but not activated B cells. This differential inhibition pattern indicates that the responses obtained from resting B cell populations are not due to their contamination with B cell blasts. Further, supernatants prepared from an activated T cell clone induce resting B cell differentiation. Two lines of evidence suggest that the activity contained in these supernatants can be attributed to interleukin (IL)-5. Activity is neutralized by monoclonal anti-IL 5; and both recombinant and affinity-purified IL-5 induce the differentiation of immediately ex vivo resting and activated B cells with comparable efficiency. Taken together, these results demonstrate that contact with T cells does not provide prerequisite signals for the induction of resting B cell differentiation. PMID- 1516623 TI - Mechanisms of resistance to Leishmania aethiopica. I. Interferon-gamma in combination with a cytokine (not tumor necrosis factor-alpha) is required, but cannot act alone in the inhibition of intracellular forms of L. aethiopica in THP1 cells. AB - Following exposure to promastigotes of various Leishmania species, mononuclear cells from non-exposed as well as potentially exposed individuals produced a cytokine response which inhibited intracellular forms of Leishmania aethiopica in a permissive monocytic cell line (THP1). Interferon-gamma (IFN-gamma), was one of the cytokines responsible for this anti-leishmanial effect. IFN-gamma was necessary for inhibition but could not act on its own inhibiting L. aethiopica. Tumor necrosis factor-alpha seemed not to be involved in the anti-L. aethiopica effect. The observed effects were in the absence of endotoxin. The results suggest that the mechanisms of killing of L. aethiopica in human cells may differ from those responsible for inhibition of other Leishmania parasites (such as Leishmania major) in mouse macrophages. Furthermore, that potentially relevant responses to Leishmania antigens may exist in normal individuals. PMID- 1516624 TI - HLA class I and II molecules present influenza virus antigens with different kinetics. AB - Human leukocyte antigen (HLA) class I and class II molecules differ with respect to their intracellular pathways and the compartments where they associate with processed antigen. To study possible consequences of these differences for the kinetics of antigen presentation by HLA class I and class II molecules, we analyzed changes in the concentrations of free intracellular calcium ions in influenza virus-specific T cell clones after recognition of specific antigen/HLA complexes. HLA class II-restricted viral antigen presentation by Epstein-Barr virus-transformed B lymphoblastoid cell lines (B-LCL) to CD4+ T cell clones started within 1 h and showed little variability, irrespective of antigen specificity or restriction element tested. In contrast, kinetics of viral antigen presentation by HLA class I molecules to CD8+ T cell clones were slower and differed for three antigen/HLA class I complexes tested. While B-LCL presented antigen by HLA-A2 and by HLA-B37 after at least 2 h, they only started to present antigen in the context of HLA-B7 after more than 4 h. This difference in kinetics did not correlate with differences in bulk transport rates of HLA-A2, HLA-B37, and HLA-B7, but seemed greatly influenced by differential rates of peptide generation. Brefeldin A treatment of B-LCL showed for both HLA class I and class II that de novo synthesized HLA molecules were involved in antigen presentation. Thus, differences between intracellular pathways of HLA class I and class II molecules may result in different kinetics of antigen presentation. PMID- 1516625 TI - Processing and presentation of intact hen egg-white lysozyme by dendritic cells. AB - Dendritic cells in lymphoid tissues are of key importance as highly specialized antigen-presenting cells for the induction of T lymphocyte responses. Conflicting results have been published regarding antigen processing of intact proteins by dendritic cells. We now report that highly purified dendritic cells isolated from H-2k mouse spleens very efficiently generated immunogenic fragments of intact hen egg-white lysozyme (HEL) protein to present to an I-Ak-restricted T hybridoma cell line, specific for HEL peptide 46-61. Dendritic cells required 100 times less HEL protein than lipopolysaccharide-induced B cell blasts for effective presentation. Uptake of 125I-labeled HEL protein by dendritic cells and inhibition of presentation of HEL protein by chloroquine treatment was observed. This indicates an endocytotic process and the involvement of acidified compartments. Since the supernatant of dendritic cells, that were incubated with intact HEL protein, contained immunogenic fragments, further evidence for processing of HEL protein by dendritic cells was obtained. When HEL protein was covalently coupled to beads, dendritic cells were not able to ingest these beads, but could still process HEL protein for presentation. This suggests cell surface processing of HEL protein, although internalization of HEL protein released from the beads cannot be excluded. Taken together, these data show that H-2k dendritic cells are capable of processing and presenting intact HEL protein. PMID- 1516626 TI - Dependency on interleukin-1 of primary human in vitro T cell responses to soluble antigens. AB - The role of interleukin (IL)-1 in antigen-specific activation of naive human T cells has been examined. Primary human T cell proliferative responses to the soluble antigen keyhole limpet hemocyanin (KLH) were decreased by neutralizing antisera to IL-1 alpha (25 +/- 7% standard error) and IL-1 beta (56 +/- 6% standard error). Inhibition by both antisera in a primary culture was usually additive. Recombinant IL-1 alpha and recombinant IL-1 beta could both re establish responses in cultures blocked by neutralizing anti-IL-1 beta. Interestingly, the susceptibility of KLH-stimulated T cell responses to inhibition by neutralizing anti-IL-1 sera decreased with time in culture. This observation suggested that T cell responses may become less IL-1 dependent as T cells become activated or primed. In support of this notion, secondary T cell responses to purified protein derivative from Mycobacterium tuberculosis (PPD) were markedly less affected by the addition of comparable amounts of the neutralizing anti-IL-1 sera. These results demonstrate that IL-1 is one of the main co-stimulators for primary T cell activation and suggest a different requirement for IL-1 in the activation of naive compared to memory human T cells. PMID- 1516627 TI - Phenotypic changes accompanying positive selection of CD4+CD8+ thymocytes. AB - We know little about the way mature CD4 (helper) and CD8 (killer) T cells develop from thymic CD4+CD8+ precursors. Here we show that small but not large CD4+CD8+ cells with high levels of the alpha beta T cell receptor (TcRhigh) result from positive selection. Neither CD4+CD8+ cells with low TcR levels nor large CD4+CD8+ thymocytes with high TcR levels differentiate in vitro. However, small CD4+CD8+ cells with high TcR levels develop in vitro into mature cells by gradually decreasing the surface levels of one or the other co-receptor and acquiring the potential to respond with proliferation to ligation of the TcR. Small CD4+CD8+ cells with high levels of a major histocompatibility complex (MHC) class I restricted transgenic TcR develop in vitro exclusively into CD4-CD8+ cells while small CD4+CD8+ TcRhigh cells with heterogeneous TcR from various mice yield both CD4 and CD8 T cells. While these experiments are consistent with an instructive model of CD4/CD8 lineage commitment they do not rule out other mechanisms which require multiple TcR-MHC ligand interactions in the generation of mature alpha beta T cells. PMID- 1516628 TI - Analysis of the roles of CD4+ and CD8+ T cells in autoimmune diabetes of NOD mice using transfer to NOD athymic nude mice. AB - The NOD mouse, which spontaneously develops insulitis and overt diabetes, is a model of autoimmune type I diabetes mellitus. For the precise analysis of the roles of CD4+ and CD8+ T cells in the pathogenesis of this mouse, these subsets must be transferred into recipients that are completely free of T cells and pathological changes. We used athymic NOD nude mice, which congenitally lack mature T cells and are free of insulitis and hyperglycemia up to the age of 60 weeks, as recipients for this purpose. To the nude recipients we transferred either one of a highly purified CD4+ or CD8+ T cell subset derived from non diabetic female NOD mice; any in vivo increase in the contaminating T cell subsets was prevented by injecting the antibody homologous to it. Most of the T cell-reconstituted recipients were treated with cyclophosphamide to promote the onset of overt diabetes. Transfer of the CD8+ T cell subset alone did not induce insulitis or hyperglycemia. In contrast, transfer of the CD4+ T cell subset alone produced insulitis, but not hyperglycemia, in all the recipients. However, the subsequent transfer of CD8+ T cells into CD4+ T cell-reconstituted recipients induced severe insulitis and hyperglycemia in almost all the recipients. In these diabetic recipients, we observed severe damage of the pancreatic islets and the infiltration of a large number of CD8+ T cells into the remaining islets; insulin secreting beta cells were no longer detected. These results suggest that CD4+ T cells play a predominant role in the development of insulitis and that CD8+ T cells migrate into the islets and are subsequently, with the aid of CD4+ T cells, differentiated into killer cells which act against beta cells. PMID- 1516629 TI - Characterization of nuclear protein binding to the interferon-gamma promoter in quiescent and activated human T cells. AB - Nuclear protein binding to the human interferon-gamma (IFN-gamma) promoter was investigated to determine the structural basis for the control of gene expression during T cell activation. DNase I footprinting of gel-shift complexes demonstrated that proteins bind to two downstream (-124 to -114 and -36 to -30) and one upstream (-534 to -486) element in the IFN-gamma gene promoter. Treatment of human peripheral blood lymphocytes or continuous T cell tumors with phorbol 12 myristate 13-acetate (PMA) plus phytohemagglutinin or calcium ionophore results in a pattern of response that is similar when using either the upstream or downstream elements. Upon induction of T cells, the lower mobility gel-shift band disappears. Yet the equivalent band which is also present in non-T cells is unperturbed after PMA + calcium ionophore treatment. The higher mobility band which is modified upon induction is restricted to the T cell lineage. Upstream and downstream elements share similar protein-binding motifs as indicated by the homology of footprinted sequences, the similarity of protein-binding patterns, and the ability of these elements to compete against each other in gel-shift protein-binding assays. Protein binding to the downstream elements appears to be interactive, since both sites are required for complex formation. When either of the two downstream elements is disrupted by site-directed mutagenesis, the higher mobility gel-shift band is diminished by an amount that is consistent with the reduction in reporter (chloramphenicol acetyltransferase) gene expression. Therefore, proteins in the ubiquitous gel-shift band appear to be associated with the inactive state of IFN-gamma, while the modified band is closely associated with the positive regulation of IFN-gamma gene expression. PMID- 1516630 TI - Anti-insulin and regulatory anti-idiotypic antibodies use the same germ-line VHIX gene. AB - In humans and in BALB/c mice, immune responses to the hormone insulin use evolutionarily related VHV (human) and VHIX (murine) gene families. To determine if these structural relationships include regulatory elements, BALB/c mice were pretreated with autologous immunoglobulin G (IgG) monoclonal antibodies (mAb) that recognize shared idiotopes on human anti-insulin antibodies and the subsequent immune response to human insulin assessed. One mAb, Id227, was found to augment and accelerate the insulin response by inducing a human idiotype that is expressed on both insulin-binding and non-insulin-binding BALB/c antibodies. Analysis of VH gene utilization by Id227 shows that it expresses a VHIX gene similar to that of anti-insulin mAb 125, but the anti-Id has no anti-insulin activity. Using DNA amplification, four germ-line VHIX genes were isolated from BALB/c liver DNA and sequence analysis shows that the anti-insulin and anti-Id are derived from the same germ-line gene. Consistent with its role as a regulatory idiotype, IgG Id227 entirely preserves germ-line sequence in the complementary determining regions and contains only three mutations in framework regions. These studies show that both structural and regulatory features of immune responses to conserved self antigens extend beyond species boundaries. PMID- 1516631 TI - Passive transfer of experimental myasthenia gravis via antigenic modulation of acetylcholine receptor. AB - Antigenic modulation of acetylcholine receptor (AChR) is considered to contribute to the reduction of endplate AChR in myasthenia gravis (MG). Yet, the pathogenic significance of this mechanism is unclear. To investigate the in vivo role of AChR antigenic modulation we examined the ability of bivalent F(ab')2 and monovalent Fab fragments of monoclonal antibody (mAb) 35 to passively transfer experimental autoimmune MG (EAMG) in rats. mAb 35 which binds at the main immunogenic region (MIR) of the AChR causes severe EAMG without being involved in channel function. Compared to the intact mAb, F(ab')2 35 proved to be less potent but still capable of inducing moderate EAMG, whereas Fab 35 were totally ineffective. Furthermore, both intact and F(ab')2 35 induced mild EAMG in complement-depleted rats. These results (a) provide evidence that antigenic modulation of endplate AChR is sufficient to generate passive transfer of EAMG and (b) further support the pathogenic potential of the anti-MIR antibodies in MG. PMID- 1516632 TI - Peptide motifs of closely related HLA class I molecules encompass substantial differences. AB - The peptides presented by major histocompatibility complex class I molecules adhere to strict rules concerning peptide length and occupancy by certain amino acid residues at anchor positions. Peptides presented by HLA-A*0201 molecules, for example, are generally nonapeptides requiring Leu or Met at position 2 and an aliphatic residue, predominantly Val, at position 9. A closely related molecule, HLA-A*0205, differing from the former at four amino acid residues, has a related but substantially different peptide motif. A*0205-presented peptides are still nonapeptides, and position 9 is still aliphatic, although it is preferentially occupied by Leu instead of Val. Position 2 not only allows aliphatic residues but also polar ones. Occupancy at position 6, considered as an auxiliary anchor in A*0201, as well as non-anchor residues at positions 3, 4, and 8 are relatively well conserved between the two peptide motifs. Thus, although a number of the T cell epitopes presented by the two HLA-A2 forms is expected to be identical, a considerable number of epitopes should be different. PMID- 1516633 TI - CD4-class II major histocompatibility complex interaction does not enhance killing by a class I-restricted CD4+CD8+ cytotoxic T cell clone. AB - As unusual tumor-specific cytotoxic T lymphocyte (CTL) clone was isolated which expressed both CD4 and CD8 molecules. The target cells for this CTL can be induced to express either class I major histocompatibility complex (MHC) alone (with dimethylsulfoxide) or both class I and class II MHC (with interferon gamma). Lysis of the tumor target depends on expression of class I MHC molecules, but does not require expression of class II MHC molecules. Furthermore, the lysis of target cells expressing both class I and class II is inhibited only by antibodies to class I (Kd), and not by antibodies to class II, demonstrating that the T cell receptor is class I restricted. We have used this CTL to assess the role of the interaction between CD4 and class II MHC in the absence of a class II restricted T cell receptor. Our data indicate that CD4-class II interaction does not contribute to recognition by T cells in the absence of binding of the T cell receptor to class II molecules. PMID- 1516634 TI - Endothelin-1 enhances vascular permeability in conscious rats: role of thromboxane A2. AB - The purpose of the present experiments was to study the effects of endothelin-1 (ET-1) on vascular permeability and the involvement of the cyclooxygenase metabolites in the vascular responses to ET-1. Bolus intravenous injection of ET 1 (0.1-1.0 nmol/kg) into conscious rats induced immediate hypotension lasting for 30 s followed by sustained dose-dependent hypertension. A low dose of ET-1 (0.1 nmol/kg) did not modify the hematocrit value but the 1.0-nmol/kg dose increased the hematocrit value from 39.7 to 44.4%. Pretreatment of the animals with BM 13505 (1 mg/kg), a thromboxane A2 (TxA2) receptor antagonist, prolonged the duration of the hypotensive response to ET-1 (1.0 nmol/kg) but had no effect on the pressor response. Pretreatment with OKY-046 (10 mg/kg), a TxA2 synthesis inhibitor, or indomethacin (10 mg/kg), a cyclooxygenase inhibitor, had no significant effect on ET-1-induced changes in blood pressure. Evans blue dye extravasation, a marker of vascular permeability, increased up to 235% over control levels in specific vascular beds including the upper and lower bronchi, stomach, duodenum and kidney of ET-1 (1.0 nmol/kg)-treated animals. Pretreatment of the animals with BM-13505, OKY-046 or indomethacin reduced by 60-100% the Evans blue extravasation in these tissues. These results suggest that the effect of ET-1 on vascular permeability is partly mediated and/or modulated by the secondary release of TxA2, whereas its action on arterial blood pressure appears to be independent from prostanoid release in conscious rats. PMID- 1516635 TI - A possible role for urinary bladder epithelium in bradykinin-induced contraction in diabetic rats. AB - Diabetes provokes a greater responsiveness of rat urinary bladder preparations to bradykinin and a greater formation and release of prostaglandin F2 alpha, without affecting prostaglandin E2 release significantly. Inhibition of cyclooxygenase by indomethacin (1 microM) inhibits the contraction elicited by bradykinin and leads to identical contractile responses of control and diabetic urinary bladder strips. Removal of the urinary bladder epithelium does not modify the contractile response evoked by bradykinin in control preparations but significantly decreases the contraction of preparations of diabetic tissues. Quantitatively, the activity of control urinary bladder strips with epithelium and the activity of diabetic preparations without epithelium are the same. More prostaglandin F2 alpha is released into the medium by urinary bladder strips devoid of epithelium in both control and in diabetic rats. These results indicate a role for epithelial cells in the smooth muscle contraction evoked by bradykinin in diabetic rats. PMID- 1516636 TI - Systemic administration of a cholecystokinin analogue, ceruletide, protects against ischemia-induced neurodegeneration in gerbils. AB - The neuroprotective action of a cholecystokinin octapeptide analogue, ceruletide, was evaluated in models of cerebral ischemia using Mongolian gerbils. Ceruletide significantly suppressed the hyperactivity and amnesia induced by ischemia when injected s.c. 30 min before 5-min occlusion of the bilateral common carotid arteries at room temperature or immediately after their reperfusion. Ceruletide also reduced behavioral changes in ischemic gerbils whose body temperature was maintained at 37 degrees C during the 3-min occlusion. In these groups, delayed neuronal cell death in the hippocampal CA1 area following ischemia was markedly attenuated by s.c. administration of ceruletide. On the other hand, ceruletide could not inhibit the behavioral changes or the neurodegeneration induced in the hippocampal CA1 area by 5-min occlusion at 37 degrees C. These findings indicate that peripheral injection of ceruletide produces a neuroprotective action against moderate cerebral ischemia, which is the first evidence suggesting the efficacy of ceruletide in neurodegenerative diseases. PMID- 1516637 TI - Evidence for a direct stimulatory effect of cibenzoline on insulin secretion in rats. AB - The effect of cibenzoline succinate, a new antiarrhythmic agent, was studied on insulin secretion in rats. Experiments were performed both in vivo and in vitro using two preparations: the isolated perfused pancreas and isolated islets. In anaesthetized rats, cibenzoline was able to increase plasma insulin levels and to reduce glycaemia. These effects were observed at 1 mg/kg i.v. in fed rats and at 3 mg/kg i.v. in fasted rats. In the isolated pancreas perfused in the presence of a slightly stimulating glucose concentration (8.3 mM), cibenzoline (2 and 6 microM) elicited a progressive and sustained insulin response in a concentration dependent manner. In the presence of a non-stimulating glucose concentration (4.2 mM), cibenzoline was ineffective at 2 microM and slightly increased basal insulin release at 6 microM. In isolated islets incubated with 8.3 mM glucose, cibenzoline (6 and 20 microM) caused a concentration-dependent stimulation of insulin release. It is concluded that cibenzoline stimulates insulin secretion by a direct action on pancreatic B cells in rats. PMID- 1516638 TI - Cholinergic/dopaminergic interaction in the rat striatum assessed from drug induced repetitive oral movements. AB - The role of striatal dopaminergic/cholinergic interactions in the regulation of oral behaviour in rats was studied using methods which resolve distinct patterns of jaw movements, allowing a more accurate quantitative and qualitative analysis. Both dopamine and acetylcholine receptor agonists given either systemically or into the ventral striatum induced repetitive oral movements. However, the cholinergic movements differed from dopaminergic movements as to pattern of activity. Oral movements induced by apomorphine (0.2 mg/kg i.v.) were potentiated by carbachol (0.1 microgram/0.2 microliters) injected into the dorsal striatum, while inhibition was observed when carbachol was injected into the ventral striatum. Pilocarpine (4 mg/kg)-induced oral movements were reduced by injecting flupentixol (10 micrograms/0.2 microliters), but not a combination of SKF 38393 (3 micrograms)+quinpirole (10 micrograms/0.2 microliter), into either the dorsal or the ventral striatum. Oral movements induced by the injection of carbachol (1 microgram/0.2 microliter) into the ventral striatum were enhanced by previous injection of this combination of dopamine receptor agonists into the same site and were inhibited by flupentixol. These results suggest that cholinergic and dopaminergic oral movements are separate behaviors and that the striatal dopamine/acetylcholine interaction in their regulation is neither simply antagonistic or synergistic, nor reciprocal. PMID- 1516639 TI - Evidence that adenosine receptors in the dog left atrium are not of the typical A1 or A2 adenosine receptor subtypes. AB - The adenosine receptors from the isolated dog left atrium were characterized using the non-selective agonists 5'-N-ethyl-carboxamidoadenosine (NECA) and adenosine, the A1-selective agonist N6-R-phenylisopropyladenosine (R-PIA), and the A2 adenosine receptor agonist C2-naphthylethoxyadenosine (NEA). The potency order of the agonists in the dog left atrium was NECA greater than adenosine greater than R-PIA = NEA. This potency order was the same as that found in the guinea pig aorta (A2) but different from that in the guinea pig left atrium (A1). In the guinea pig left atrium the potency order was NECA greater than R-PIA greater than adenosine much greater than NEA. The negative inotropic responses to NECA in the dog left atrium were antagonised by the non-selective antagonist 8 phenyltheophylline (8-PT) and the A1-selective antagonists 1,3-dipropyl-8 cyclopentylxanthine (DPCPX) and N6-endonorbornan-2-yl-9-methyladenine (N-0861), giving pKB values of 6.3, 7.3 and 5.1, respectively. These values are significantly different from those estimates determined in either the guinea pig left atrium or guinea pig aorta. The potency order of the agonists and the relatively low potencies of the A1-selective antagonists suggests that the adenosine receptors in the dog left atrium are not of the classical A1 adenosine receptor subclass and may instead be more closely related to the A2 adenosine receptor. PMID- 1516640 TI - Effects of NIK-247 on CO-induced impairment of passive avoidance in mice. AB - The effect of NIK-247 on carbon monoxide (CO)-induced amnesia were investigated. A step-down type passive avoidance task with mice was used to compare the effects of NIK-247 with those of tacrine. Two types of CO-induced amnesia model, acute and delayed models, were used. The acute amnesia model was developed using mice exposed to CO before memory consolidation, just after training, and a retention test carried out 24 h after training. The delayed amnesia model was prepared 7 days after CO exposure even when the animals were exposed to CO 4 h after training, after memory had consolidated. NIK-247 administered post-training at 0.03-0.3 and 3 mg/kg or pre-retention test (24 h after training) at 0.3 and 10 mg/kg attenuated the acute amnesia. In addition, NIK-247 (0.03, 0.1, 1 and 10 mg/kg) and tacrine (0.03, 0.1 and 1 mg/kg) administered before the retention test (7 days after CO exposure) improved retrieval in the delayed amnesia model. Tacrine (0.01-0.3 and 3 mg/kg), administered post-training, attenuated the acute amnesia but pre-retention test administration did not. The dose-response curves for NIK-247 and tacrine were biphasic bell-shaped. These results indicated that NIK-247 has an improving effect on hypoxia-induced acute and delayed cognitive dysfunction, and suggest that NIK-247 has promise as a nootropic drug for therapy of memory deficits in patients with cerebrovascular-type dementing disorders. PMID- 1516641 TI - Interleukin-1 alpha-stimulated fibroblast eicosanoid synthesis is not mediated by interleukin-6. AB - Adherent human dermal fibroblasts secreted interleukin-6, prostaglandin E2, prostaglandin I2 and 15-hydroxyeicosatetraenoic acid (assayed by radioimmunoassay) during a 3 h incubation period. Although human dermal fibroblasts did not secrete interleukin-1 alpha or interleukin-1 beta, human recombinant interleukin-1 alpha stimulated arachidonic acid metabolism and interleukin-6 synthesis. This effect was, at least partly, dependent on de novo protein synthesis. In contrast, human recombinant interleukin-6 had no effect on the synthesis and release of the eicosanoids measured. Human recombinant interleukin-1 alpha also stimulated the metabolism of [14C]arachidonic acid, but only if fibroblast were pre-incubated with the cytokine for three hours. Our data indicate that (a) fibroblasts secrete interleukin-6 but not interleukin-1, (b) interleukin-1 alpha, but not interleukin-6, stimulates fibroblast arachidonic acid metabolism and (c) the mechanisms involved in the metabolism of endogenous arachidonic acid are more sensitive to human recombinant interleukin-1 alpha than those involved in metabolism of the exogenous substrate. PMID- 1516642 TI - Affinity changes in muscarinic acetylcholine receptors in the rat brain following acute immobilization stress: an autoradiographic study. AB - The modifications in rat brain muscarinic acetylcholine receptors induced by acute immobilization stress lasting 10 min or 2 h were analyzed by quantitative in vitro autoradiography. [3H]N-Methylscopolamine ([3H]NMS) was used as a ligand. Immobilization stress for 10 min did not produce any significant change in the properties of [3H]NMS binding sites throughout the brain. In contrast, 2 h immobilization caused a significant increase in receptor affinity (Kd) without modification in the maximal number of receptors (Bmax) in several brain areas such as the caudate-putamen, cortical layers and CA1 field of the hippocampus, among others. These results, found even in animals killed immediately after the end of the immobilization sessions, suggest that immobilization stress induces supersensitivity of muscarinic receptors in certain cholinergic pathways in rat brain. PMID- 1516643 TI - 5-Hydroxytryptamine stimulates 45Ca2+ uptake by human umbilical vein endothelial cells in culture: mediation by 5-HT2 receptor subtypes. AB - In cultured human umbilical vein endothelial cells, 5-HT and alpha-methyl 5-HT stimulated [45Ca2+] uptake in concentration-dependent manner, whereas the 5-HT1 agonists, m-CPP (1-(3-chlorophenyl)piperazine and 2-MPP (1-(2 methoxyphenyl)piperazine), were without effect. In turn, 5-HT-stimulated [45Ca2+] uptake was inhibited in concentration-dependent manners by the 5-HT receptor antagonists ketanserin (5-HT2), LY 53,857 (5-HT2) and methiothepine (5-HT1/2) and to a lesser degeree by MDL 72222 (5-HT3) and BRL 43694 (5-HT3) whereas (+/-) propranolol (5-HT1) was without effect. These data indicate that 5-HT stimulates Ca2+ uptake by endothelial cells via activation of a 5-HT2 receptor subtype. 5-HT was without effect on de novo prostacyclin (PGI2) synthesis over the concentration of 5-HT that elicited [45Ca2+] uptake. Since 5-HT did not stimulate PGI2, an event associated with an increase in levels of intracellular Ca2+, it is postulated that the uptake of 45Ca2+ reflects changes of Ca2+ at the level of the plasma membrane rather than on intracellular changes. 5-HT-stimulated Ca2+ uptake may be of relevance to endothelium-dependent relaxation, vascular permeability and endothelial repair and proliferation. PMID- 1516644 TI - Effects of endothelin on intracellular Ca2+ and contractility in single ventricular myocytes from the ferret and human. AB - We investigated the role of endothelin-1 on peak intracellular Ca2+ ([Ca2+]i) and peak shortening of ventricular myocytes (loaded with indo-1/AM) from failing human hearts. 10 nM of ET-1 significantly increased the cell peak shortening (84 +/- 29%, P less than 0.05) without significantly increasing the peak [Ca2+]i (15 +/- 7%, P greater than 0.05). Further studies on ferret cardiac myocytes indicated that in addition to producing dose-dependent (0.1-10 nM) significant increases in peak shortening (max 55 +/- 6% P less than 0.01) and non-significant increases in peak [Ca2+]i (max 35 +/- 19%, P greater than 0.05), endothelin-1 significantly shifted the peak [Ca2+]i-peak shortening curve upward. The results suggest that endothelin-1 acts directly on human and ferret cardiac myocytes to produce a positive inotropic effect that may predominantly be due to an enhanced myofilament Ca2+ responsiveness. PMID- 1516645 TI - L-687,306: a functionally selective and potent muscarinic M1 receptor agonist. AB - The oxadiazole L-687,306 is a high affinity muscarinic agonist with a N methylscopolamine/oxotremorine-M binding profile predictive of a partial agonist. L-687,306 showed marked selectivity in functional pharmacological assays. L 687,306 was a partial agonist at muscarinic M1 receptors in the rat ganglion but a high affinity competitive antagonist at guinea-pig cardiac M2 and ileal M3 muscarinic receptors. This compound gives an opportunity to study receptor reserve involved in muscarinic receptors in vitro and in vivo. PMID- 1516646 TI - Effect of different subtypes of cognition enhancers on long-term potentiation in the rat dentate gyrus in vivo. AB - The effect of four drugs considered as cognition enhancers on the amplitude of the population spikes and on the long-term potentiation (LTP) evoked by perforant path stimulation was investigated in rat dentate gyrus in vivo. LTP was characterized by the absolute increase in the amplitude of the population spikes, which were expressed in mV, contrary to the widely used percentage value, because the absolute increase was independent of the pretetanus level, whereas the percentage increase was found to be negatively correlated with it. Intravenous administration of the drugs (piracetam 500 mg/kg, hydergine 2 mg/kg, vinpocetine 0.1 and 5 mg/kg and physostigmine 0.01 and 0.1 mg/kg) did not influence the amplitude of the population spikes itself. Piracetam and hydergine did not have an effect on LTP, while vinpocetine and physostigmine altered LTP in a similar manner. The higher doses of the two latter drugs, administered 5 min before tetanic stimulation, induced a significant potentiation of LTP, whereas a significant inhibition of LTP was obtained when the drugs were administered 30 min before tetanic stimulation. Based on the results obtained from guinea pig hippocampal slices, an LTP-potentiating effect of all compounds tested could have been anticipated, but this was not supported by our data. The apparent contradiction between the in vivo and in vitro results is discussed. PMID- 1516647 TI - Effects of bombesin, of a new bombesin agonist (BIM187) and a new antagonist (BIM189) on food intake in rats, in relation to cholecystokinin. AB - To study the mechanism by which bombesin induces satiety, we studied the effect of two new peptides, BIM187, a bombesin agonist, and BIM189, a bombesin antagonist, on food intake in rats fed 6 h a day. BIM187 at 4 micrograms/kg, significantly reduced food intake at 30 min, but did not change the total 6-h food intake. BIM189 (10 mg/kg), had no effect on food intake when administered alone, even at high doses (20 mg/kg). BIM189 selectively reduced bombesin-induced satiety but had no effect on satiety induced by BIM187. To examine the extent to which the satiety effect of bombesin or related peptides depends on the release of cholecystokinin (CCK), we studied the ability of CCK antagonists, BIM18216 and L364718, to reduce satiety induced by bombesin and BIM187. Neither BIM18216 nor L364718 alone had an effect on the 30-min food intake. They were not able to reverse the effect of bombesin on food intake. In our model, bombesin seems to act on satiety by a mechanism independent of CCK. PMID- 1516648 TI - Tolerance and withdrawal to chronic morphine treatment in the week-old rat pup. AB - Chronic treatment of adult animals with morphine results in tolerance but there are fewer reports on the effects of chronic opiates during ontogeny. The present experiments assessed the development of morphine-induced tolerance and withdrawal in infant rats. Pups were injected with morphine twice daily from ages 1-7 days and then tested on day 7 for morphine-induced analgesia in a hot-water immersion test, and separation-induced ultrasonic vocalizations in response to isolation from the dam and littermates at 7 and 10 days of age. Tolerance occurred to the analgesic effects of morphine but not to its suppression of ultrasonic vocalizations. Separation-induced vocalizations were greatly increased in chronic morphine-treated pups following naltrexone-precipitated withdrawal at 7 days of age. The increase in ultrasonic vocalizations following naltrexone treatment in morphine exposed pups may be a developmentally unique sign of opiate withdrawal. PMID- 1516649 TI - In rat brain amoxapine enhances dopamine metabolism: pharmacokinetic variations of the effect. AB - When rats were given i.p. amoxapine, the drug was biotransformed to 7 hydroxyamoxapine, but not to 8-hydroxyamoxapine. The maximal concentrations of amoxapine and 7-hydroxyamoxapine in the serum and brain were found 30 min after the single injection, and the concentration of the former in the brain was higher than that of the latter. During the chronic treatment the concentration of amoxapine in the brain was much higher than that of 7-hydroxyamoxapine. A single administration of amoxapine increased the brain levels of dihydroxyphenylacetic acid and homovanillic acid. Their highest levels were observed 6 h after the injection. Repeated administration reduced the increases; chronic treatment caused tolerance to the enhancing effects on dopamine (DA) metabolism. Tolerance was observed in both striatum and hippocampus, but not in frontal cortex and hypothalamus. Single or chronic injection did not appear to change the level of DA in the brain. Amoxapine itself could be chiefly responsible for the enhancement of DA metabolism. In addition, the level of 3-methoxy-4 hydroxyphenylethyleneglycol in brain decreased transiently right after the injection of amoxapine, but the norepinephrine level did not seem to change following single or chronic administration of amoxapine. PMID- 1516650 TI - The distribution of 5-HT3 recognition sites in the marmoset brain. AB - The distribution of the binding of [3H]GR65630 (0.2 nM) to putative 5-HT3 recognition sites in the brain of the common marmoset was assessed using autoradiography. Specific binding was heterogeneously distributed with the highest densities found in discrete nuclei of the lower medulla (nucleus tractus solitarii, dorsal motor nucleus of the vagus nerve, nucleus of spinal trigeminal nerve tract and the area postrema). In forebrain areas, relatively high binding densities were located in the medial habenula nucleus and the hippocampus (CA3, CA4 and fascia dentata). Low levels of specific binding in the rest of the forebrain hindered quantification. PMID- 1516651 TI - Analysis of the vasorelaxant action of jatrophone in the isolated aorta of the rat: influence of potassium channel blockers. AB - The mechanism underlying the relaxant response of rat aortic rings to the diterpene jatrophone was investigated. Jatrophone (3 and 10 microM) did not affect acetylcholine-induced endothelium-dependent relaxations, but caused concentration-dependent inhibition of noradrenaline (NA)-induced concentrations in unrubbed, and to a lesser extent, in denuded rings. Jatrophone (30 microM) fully prevented responses to angiotensin II and NA, while responses to KCl (up to 220 mM) were unaffected. In depolarizing medium (KCl 40 mM), jatrophone (3-30 microM) antagonized Ca(2+)-induced contractions in a concentration-dependent and noncompetitive manner, while verapamil (10-100 nM) caused a concentration dependent, rightward displacement and depression of the Ca2+ concentration response curve. Jatrophone (1 to 300 microM) concentration dependently relaxed rat aortic rings precontraction with either NA (1 microM) or KCl (80 mM), yielding EC50 s of 11 and 24 microM, respectively. These relaxant responses to jatrophone were unaffected by glibenclamide (1 microM), but the concentration response curve was displaced to the right (2- to 8-fold) by other K+ channel blockers such as tetraethylammonium (10 and 30 mM), 4-aminopyridine (3 and 10 mM) or procaine (1 and 3 mM). These results indicate that jatrophone relaxes the rat aorta, at least in part, by activating K+ channels distinct from the ATP sensitive subtype. Since jatrophone, like verapamil, relaxed preparations contracted with KCl and inhibited Ca(2+)-induced contractions in depolarized preparations, this diterpene may also block Ca2+ influx through voltage-sensitive channels. However, additional actions of jatrophone on receptor-operated Ca2+ channels causing Ca2+ efflux and/or release cannot be fully ruled out. PMID- 1516652 TI - Pressor response to posterior hypothalamic administration of carbachol is mediated by muscarinic M3 receptor. AB - Unilateral microinjection of the acetylcholine receptor agonist carbachol into the posterior hypothalamic nucleus evokes a pressor response in the conscious, freely moving rat. To further localize this response 3.3 or 5.5 nmol of carbachol was microinjected in a volume of 50 nl directly into and outside the region of the posterior hypothalamic nucleus. Administration of carbachol outside the posterior hypothalamic nucleus failed to evoke a change in blood pressure indicating that the carbachol-induced pressor response is mediated from the posterior hypothalamic nucleus. Since posterior hypothalamic administration of atropine completely blocks the carbachol-induced increase in blood pressure and atropine blocks the three pharmacologically identified muscarinic receptor subtypes, methylatropine and progressively more selective muscarinic antagonists were administered into the posterior hypothalamic nucleus prior to 5.5 nmol of carbachol. Microinjection of the M1/M2/M3 muscarinic antagonist methylatropine (0.19-12.5 nmol), the M1/M3 antagonist 4-DAMP (4-diphenylacetoxy-N methylpiperidine; 0.9-3.6 nmol), the M1 antagonist pirenzepine (9.5-38 nmol), the M2 antagonist methoctramine (5.5-44 nmol), or the M3 antagonist p-F-HHSiD (para fluoro-hexahydro-sila-difenidol; 2.1-8.3 nmol) inhibited the peak increase in mean arterial pressure and the area under the curve of the change in mean arterial pressure versus time plot in a dose-dependent manner. Log ID50s calculated for the antagonists from the dose-response curves were found to correlate significantly with the log Kis of the antagonists for the muscarinic M3 receptor subtype. These results demonstrate that the increase in mean arterial pressure evoked by microinjection of carbachol into the posterior hypothalamic nucleus is mediated by the muscarinic M3 receptor. PMID- 1516653 TI - Inositol hexakisphosphate excites rat medullary sympathoexcitatory neurons in vivo. AB - Inositol hexakisphosphate (IP6) was microinjected into the rostral ventrolateral reticular nucleus or iontophoresed onto reticulospinal sympathoexcitatory neurons of the nucleus in anesthetized rats. IP6 (5-500 pmol) induced a dose-dependent potent and prolonged elevation of arterial pressure which was mimicked by microinjection of ethyleneglycol-bis (beta-aminoethylether)N,N,N',N'-tetraacetic acid (EGTA), while myo-inositol was ineffective. Iontophoretic application of IP6 and EGTA excited the medullary sympathoexcitatory neurons but myo-inositol had no effect. The effect of IP6 on firing rate of the sympathoexcitatory neurons was abolished by co-administration of Ca2+ ions onto these neurons. The results indicate that IP6 acts extracellularly to excite the medullary sympathoexcitatory neurons. The excitatory actions of IP6 may depend, at least in part, on a calcium chelating action. Chelation of extracellular Ca2+ might be a physiological action of IP6. PMID- 1516654 TI - Pharmacological characterization of inositol 1,4,5-trisphosphate binding sites: relation to Ca2+ release. AB - Two subcellular fractions, one enriched in plasma membranes and the other in endoplasmic reticulum membranes, were obtained from WRK1 cells using a combination of differential centrifugations and Percoll gradient fractionation. Specific inositol 1,4,5-trisphosphate (Ins(1,4,5)P3) binding sites were detected in these two preparations. Endoplasmic reticulum membranes exhibited a binding capacity which was about 5-fold higher than that of plasma membranes. Dose dependent Ins(1,4,5)P3 binding was determined. Experimental data obtained with endoplasmic reticulum membranes could be adequately fitted with a two-site model (a high-affinity binding site with Kd and Bmax values of 0.7 +/- 0.15 nM and 12.9 +/- 5 fmol/mg protein and a low-affinity binding site with Kd and Bmax values of 44.2 +/- 14.6 nM and 143 +/- 43 fmol/mg protein). Both the high- and low-affinity binding sites were selective for Ins(1,4,5)P3. Besides Ins(1,4,5)P3, Ins(1,3,4,5)P4 also discriminated between the two populations of sites while heparin interacted with the high- and low-affinity binding sites with the same affinity. Ins(1,4,5)P3-induced calcium release from endoplasmic reticulum vesicles was determined by monitoring the calcium concentration in the extravesicular compartment with fura-2. Under experimental conditions where the degradation of Ins(1,4,5)P3 was reduced (incubation at 0 degrees C), a high affinity Ins(1,4,5)P3-induced calcium release (apparent Kact around 20 nM) could be demonstrated. These results suggest that in WRK1 cells, the endoplasmic reticulum is a major site for Ins(1,4,5)P3 action and that the high-affinity binding sites located on the endoplasmic reticulum membranes may contribute to the physiological regulation of the cytosolic free calcium concentration. PMID- 1516655 TI - Serotonin-binding proteins in the bovine cerebral cortex: interaction with serotonin and catecholamines. AB - The soluble serotonin-binding proteins (SBP) present in bovine frontal cortex are very similar to those reported in rat brain. Binding of [3H]serotonin to SBP, present in ammonium sulphate-precipitated proteins from bovine cortex, requires Fe2+ but not Fe3+. In the presence of an optimal concentration of Fe2+ (0.1 mM), bovine SBP behave as a single class of non-cooperative sites for [3H]serotonin binding (Bmax = 120 +/- 12 pmol/mg protein, KD = 0.12 +/- 0.04 microM, n = 3). Binding of [3H]serotonin is decreased by nucleotides and by reagents which modify sulfhydryl groups and reduce disulfide bonds and by metal ion chelators. Serotonin analogs possessing an hydroxyl group on the indole ring and catecholamine analogs possessing an intact catechol moiety are effective competitors (Ki from 0.1 to 0.3 microM). In both cases, the aliphatic amino group does not contribute to the binding, but the affinity is strongly decreased if aromatic hydroxyl groups are methoxylated. Catecholamine-SBP interactions can also be demonstrated directly by binding experiments. Binding of [3H]dopamine is greatly enhanced by Fe2+, Cu2+ and Mn2+, but not by Fe3+. The Fe(2+)-dependent binding component of [3H]dopamine is saturable (Bmax = 279 +/- 64 pmol/mg protein, KD = 0.19 +/- 0.02 microM, n = 3), and possesses the same physicochemical properties as SBP: it elutes immediately after the void volume on a Sephacryl S100 HR (1.6 x 140 cm) gel filtration column (reflecting aggregation) and it migrates with an apparent molecular weight of 57-58 kDa on native polyacrylamide gel electrophoresis. Whereas the serotonin-storing role of SBP in serotonergic neurons has already been well documented, the present data advocate that these proteins may also possess catecholamine-storing properties. PMID- 1516656 TI - Agonist-independent inhibition of G protein activation by muscarinic acetylcholine receptor antagonists in cardiac membranes. AB - Agonist activation of muscarinic acetylcholine (mACh) receptors in porcine atrial membranes stimulates binding of the GTP analog, guanosine 5'-O-[gamma thio]triphosphate (GTP[S]), to membrane G proteins. In contrast, atropine as well as several other mACh receptor antagonists reduced the binding of GTP[S] below basal values, both in the absence and presence of the agonist carbachol, by a similar maximal extent (about 25%). Evidence is presented that this inhibitory action of atropine was not due to an antagonism of endogenous acetylcholine. Similar to agonist-induced stimulation, antagonist-induced inhibition of GTP[S] binding required the presence of GDP and Mg2+. On the other hand, addition of salts, e.g. NaCl, amplified agonist but reduced antagonist effects on GTP[S] binding. The data presented suggest that agonist-unliganded mACh receptors interact with and activate G proteins in native cardiac membranes and that antagonist binding induces a conformational change of the receptor, which then either does not interact with G proteins or which prevents GDP release from and subsequent GTP[S] binding to G proteins. PMID- 1516657 TI - Orthodontic magnets: effects on gingival epithelium and alveolar bone in monkeys. AB - The purpose of the present study was to examine soft and hard oral tissues in contact with or close to orthodontic magnets following an extended exposure time. Two male monkeys were used in the experiment. Individual silver splints covering the teeth from 17 to 27 in the upper jaw and 32-42 in the lower jaw were made. Co5Sm magnets were inserted with cold-curing acrylic buccally and lingually in the splints. The monkeys were injected with tetracycline at the start of the experiment and after 4 weeks. The epithelial thickness in buccal and lingual mucosa under the magnets and corresponding sites on the control side were estimated. The intensity of tetracycline fluorescence in the bone under the magnets and corresponding control sites was assessed semiquantitatively. A thinner epithelium compared to the controls and a patchy tetracycline incorporation in the bone adjacent to orthodontic magnets in contrast to a homogeneous tetracycline fluorescent pattern in the controls were the most conspicuous findings. It cannot be excluded that the magnetic field or corrosion products from the magnetic material influenced vital processes in the epithelium and the bone close to the magnets. However, it cannot be concluded from the present study what cellular processes were affected. PMID- 1516658 TI - Distalization of maxillary first and second molars simultaneously with repelling magnets. AB - The aim of this study was to analyse the clinical and the dentofacial effects of using repelling SmCo5 magnets for distalization of maxillary first and second molars simultaneously. Ten consecutive patients, aged 12.0-15.6 years, with Class II malocclusion and moderate space deficiency in the upper jaw were orthodontically treated using prefabricated repelling SmCo5 magnets. The magnets were attached buccally in the premolar and first molar area to a fixed orthodontic applicance. When the magnets were activated, the molars could move freely distally. The tooth movements were analysed by measurements on dental casts, lateral photographs of dental casts, and lateral skull radiographs before and after treatment. The mean treatment time was 16.6 weeks and all maxillary molars could be distalized to a Class I relationship. The mean molar crown movement was 4.2 mm, and the maxillary first molars tipped distally and rotated disto-buccally by 8.0 and 8.5 degrees, respectively. The reciprocal forces resulted in a slightly increased inclination of the upper incisors. It was found that simultaneous distalization of first and second maxillary molars with repelling magnets could be an alternative to ordinary orthodontic treatment methods. As the molar distalization was achieved during a relatively short period, occlusal adjustment, including uprighting and derotation of the maxillary molars as well as post-treatment retention, seems recommendable. PMID- 1516659 TI - Dental arch development in a set of triplets. AB - A set of male triplets, of whom the two youngest appear to be identical, has been followed and recorded on plaster casts from 1 month to young adulthood. Measurements of tooth size, arch breadth, length, and circumference, as well as arch relationship, were made at five stages of development. There was a general tendency for the identical pair to become more similar after puberty, and less like their dizygotic brother. Attention is drawn to the potential value of a longitudinal study on a sample of sets of similar sex triplets each containing two identical individuals. PMID- 1516660 TI - Effect of the vertical force component of Class II elastics on the anterior intrusive force of maxillary archwire. AB - Class II elastics are usually employed in the treatment of excessive overbite and overjet with the Begg technique. The effect of Class II elastics on bite opening and the extent of such an effect is uncertain. This article, based on measurements of 30 cases, illustrates that the effect of the vertical component of force from Class II elastics in reducing the intrusive force generated by the anchor bands in the upper archwire is less than previously believed. The position of the circles in the archwire for intermaxillary elastics has the greatest influence on the anterior intrusive force of the upper archwire. The direction of the Class II elastics and the length of the dental arch (a negative correlation) came second, while the force actually exerted by the elastics had the smallest influence. It is, therefore, suggested that the position of the intermaxillary elastic circles should be located according to the differing clinical objectives. PMID- 1516661 TI - Long-term effects of Herbst treatment in relation to normal growth development: a cephalometric study. AB - The aim of this study was to evaluate the short- and long-term effects of Herbst appliance treatment in relation to normal growth and development. The sample consisted of 32 subjects (16 boys and 16 girls) with a Class II, division 1 malocclusion treated successfully with the Herbst appliance for an average period of 7 months. The patients were reinvestigated 6 months post-treatment when the occlusion had settled and at the end of the growth period, an average of 6.7 years (SD = 1.1 years) after therapy. The control group comprised of 32 subjects (16 boys and 16 girls) with excellent occlusion (Bolton Standards). Sagittal, skeletal, and dental changes occurring during three observation periods were evaluated on lateral cephalograms in centric occlusion. On a long-term basis, Herbst treatment improved the sagittal jaw base relationship, but did not normalize it. The sagittal dental arch relationship, on the other hand, was almost normalized. PMID- 1516662 TI - The application of computerized tomography (CT) in cases of impacted maxillary canines. AB - A comparison is made between conventional X-rays and computerized tomography (CT) based on eight patients with thirteen impacted upper permanent canines. The use of CT yields information which is much more detailed than that observed on conventional X-rays, such as: pathological resorption on adjacent teeth caused by aberrant canines; the localization of the injury and the position of the canine in relation to one or both incisors. The amount of radiation per exposure is still rather high for the CT (Koster and Ewen, 1986). Further research is necessary in order to reduce this exposure and to determine the appropriate and most effective use of CT in the dental field. PMID- 1516663 TI - Malocclusion traits and articulatory components of speech. AB - The aim here was to determine the effects of particular types of malocclusion including the effects of combinations of different occlusal anomalies on speech articulation. Occlusal anomalies and articulatory speech disorders, a diagnosis based on errors in place of articulation, were determined for 451 students, mean age 23 years. The present results showed that risk ratios for producing consonants too far anteriorly was greater by 4.5 times for subjects with mesial occlusion, 3.7 times for those with mandibular overjet, 3.4 times for subjects with incisal open bite and 1.7 for those with lateral cross-bite compared to individuals without those occlusal anomalies. This study suggests that incisal open bite alone is rarely associated with articulatory speech disorders, but if present they tend to be mild. Incisal open bite combined with other occlusal anomalies, especially with mesial occlusion, is related to more severe misarticulations of consonants. PMID- 1516664 TI - Dirofilaria immitis: do filarial cyclooxygenase products depress endothelium dependent relaxation in the in vitro rat aorta? AB - Endothelial cells modulate the function of their underlying smooth muscle. Thus, altered endothelial behavior could be important in the pathogenesis of vascular and lymphatic diseases, including human and animal filariasis. Endothelium dependent relaxation is depressed in both in vivo canine femoral artery of dogs infected with Dirofilaria immitis and in vitro rat aorta exposed to adult D. immitis. The experiments reported here were designed to determine if filarial cyclooxygenase products could depress endothelium-dependent relaxation in vitro. Pretreatment of the parasites, but not the vascular ring, with either indomethacin or aspirin, prevented filarial-induced depression of relaxation. Analysis of heartworm-conditioned medium by gas chromatography--mass spectrometry revealed two peaks in the biologically active medium that were not present in the control. One peak had a retention time and chromatographic profile characteristic of derivatized PGD2 standard, and the other was not identified. Incubation of the vascular ring with PGD2 mimicked filarial-induced depression of endothelium dependent relaxation at low, but not high, concentrations of acetylcholine. Thus, filarial PGD2 may be involved in altered endothelium-dependent relaxation seen in heartworm-infected dogs. PMID- 1516665 TI - Schistosoma mansoni: mortality, pathophysiology, and susceptibility differences in male and female mice. AB - In parallel studies of Schistosoma mansoni infections in male and female CBA/J mice, major sex-related differences are seen in the development of infection and disease. Upon equal subcutaneous exposures to 45 cercariae female mice present a more severe clinical course with consequent higher mortality than male mice. By 12 weeks of infection, more than 80% of female mice die, while less than 20% of infected males succumb to infection. This greater index of mortality is apparently due to the higher susceptibility of female mice to the development of adult worms. Exposed to 45 cercariae, virtually all females develop patent infections, but 8-34% of male mice do not do so. Also, the recovery rate of adult worms per cercariae from female mice is much higher than that from males, indicating that schistosomula are more successful in developing into adult worms in female mice. Additional studies indicate that this dichotomy of schistosomiasis in the sexes is not restricted to mice of the CBA/J strain, but also occurs in C57BL/6 and outbred CF1 strain mice. PMID- 1516666 TI - Fasciola hepatica: host responders and nonresponders to parasite glutathione S transferase. AB - Fasciola hepatica glutathione S-transferase (FhGST) was isolated from adult worms by glutathione agarose affinity chromatography. SDS-PAGE shows three proteins of M(r) ranging from 29-27.8 kDa. Western immunoblot analyses using SDS-PAGE separated adult worm extracts and probed with a rabbit anti-FhGST antiserum reveal two bands in the same M(r) range. Mice and rabbits immunized with purified FhGST develop copious amounts of anti-FhGST antibodies. Moreover, antisera to F. hepatica adult worms and excretion-secretion products also react with FhGST. Cross-reactivity with schistosomes is evidenced in the reactivity with FhGST of anti-Schistosoma mansoni adult worm antisera and, to a lesser extent, antisera to S. mansoni-soluble egg antigens. The time of appearance of anti-FhGST antibodies in different species of animals infected with F. hepatica was determined. Sheep and a New Zealand white rabbit developed anti-FhGST antibodies detectable by ELISA as early as 2 weeks postexposure with F. hepatica. However, neither mice nor calves infected with F. hepatica developed antibodies to FhGST through the 5 10 weeks of infection tested. But mice infected with S. mansoni developed anti FhGST cross-reacting antibodies by 6 weeks of infection. Calves immunized with a Fasciola/Schistosoma cross-reactive, cross-protective antigen complex in which a 12,000-kDa protein (Fh12) has been shown to contain immunoprophylactic activity, also developed antibodies to FhGST. Since FhGST is a novel potential vaccine, its protection-inducing capability in a multivalent vaccine combined with Fh12 clearly warrants study. In summary, it appears that hosts with fascioliasis are either responders to FhGST (rabbits, sheep) or nonresponders (mice, cattle), offering interesting models for studying the immune response. PMID- 1516667 TI - Leishmania major: differential regulation of the surface metalloprotease in amastigote and promastigote stages. AB - During its life cycle, the protozoan parasite Leishmania major alternates from an intracellular amastigote form in the mammalian host to a flagellated promastigote form in the insect vector. The expression of the surface metalloprotease (PSP) during differentiation in vitro was investigated by Western and Northern blots, by immunoprecipitation of cells metabolically labeled with [35S]methionine or labeled at the surface with radioactive iodine, and by quantification of the proteolytic activity in substrate-containing polyacrylamide gels. We report that the surface metalloprotease is down-regulated at both the mRNA and the protein level in amastigotes, where it represents less than 1% of the equivalent proteolytic activity detected in promastigotes. A significant amount of mRNA is detected 4 hr after the onset of differentiation. The expression of the protease begins at that time and reaches steady state 8 hr later. The synthesis of PSP precedes the complete morphological differentiation to the promastigote stage and the appearance of the lipophosphoglycan, another major promastigote surface component. In contrast to PSP, a family of mercaptoethanol-activated proteases present in the amastigote exists only at a reduced level in the promastigote. The confinement of the surface metalloprotease to the insect stage of the parasite suggests that it has no physiological function in the parasitism maintenance of mammalian host macrophages. PMID- 1516668 TI - Plasmodium falciparum: a simple polymerase chain reaction method for differentiating strains. AB - Laboratory studies of the protozoan parasite Plasmodium falciparum have been hampered by difficulties in defining differences between isolates. We have developed a method based on the polymerase chain reaction (PCR) that allowed us to identify quickly the various strains with which we routinely work. We also adapted methods for easily purifying enough DNA to produce a PCR product from a small volume of culture: 100 microliters of an in vitro culture infected at 1% parasitemia. The primers were chosen from conserved regions flanking the variable repeats in four cloned genes, RESA, MSA-1, MSA-2, and CSP. The PCR products amplified from three of these genes differed in size and allowed us to identify particular isolates on this basis alone. The variation was between strains, and not a reflection of genetic instability during in vitro culture of one isolate. The method is sufficiently sensitive to detect a 1% contamination of one strain with another, an advantage for monitoring the integrity of strains when different isolates are grown in the same laboratory. The technical ease and speed of this assay and the small amount of culture required make it ideal for monitoring strains in the laboratory. PMID- 1516670 TI - Echinostoma paraensei and Schistosoma mansoni: adherence of unaltered or modified latex beads to hemocytes of the host snail Biomphalaria glabrata. AB - Hemocytes derived from a strain (13-16-R1) of Biomphalaria glabrata resistant to Schistosoma mansoni were significantly more likely to bind untreated latex beads than hemocytes from the schistosome-susceptible M line strain. Beads preincubated in 13-16-R1 plasma were more readily bound by both 13-16-R1 and M line hemocytes than beads preincubated in M line plasma. Beads preincubated in plasma derived from snails of either strain infected with the trematode Echinostoma paraensei were more readily bound by hemocytes than beads preincubated in plasma from control snails of the corresponding strain. Plasma from snails exposed to S. mansoni did not have a similar effect. Throughout these experiments, beads receiving a particular treatment were consistently bound at higher rates by 13-16 R1 than M line hemocytes. SDS-PAGE of plasma components eluted from beads revealed differences between treatments, particularly in diffuse bands falling into two groups, of 75-130 and 150-220 kDa. The results indicate that both hemocytes and plasma components from the two host strains differ and identify plasma molecules deserving of additional study as possible modulators of hemocyte effector functions. Also, S. mansoni and E. paraensei provoked different responses in the same host snail. PMID- 1516669 TI - Dirofilaria immitis: proteases produced by third- and fourth-stage larvae. AB - A model of cutaneous extracellular matrix was used to determine if live Dirofilaria immitis larvae secrete proteases which are active at physiological pH and capable of degrading macromolecules found in cutaneous tissue. After 72 hr, 100 third-stage larvae (L3) degraded 24% of the total matrix, while fourth-stage larvae (L4) degraded 10%. A sharp increase in the amount of matrix degraded by L3 corresponded with the onset of the molting process. L3 and L4 degraded comparable amounts of the glycoprotein and elastin components of the matrix, but molting L3 degraded nearly twice the amount of the collagen component (62% vs 35%). Characterization of proteases present in larval-soluble extracts and excretory secretory products using synthetic substrates and protease inhibitors demonstrated cysteine-protease and metalloprotease activity. Cysteine protease activity was found in whole worm extracts of both L3 and L4. Metalloprotease was secreted at higher levels by molting L3, but was also secreted by L4. Partial separation of the metalloprotease by size-exclusion chromatography indicated that the molecular weight of the native enzyme was in the 49-54 kDa range. The cysteine protease activity was demonstrated in fractions corresponding to 34-39 kDa. The biological function of the D. immitis larval proteases remains to be conclusively determined; however, these data suggest that they are involved in degradation of components of cutaneous tissue and in the molting process. PMID- 1516671 TI - Follow-up of patent and subpatent parasitemias and development of muscular lesions in mice inoculated with very small numbers of Trypanosoma cruzi. AB - A sequential analysis of patent and subpatent parasitemias, mortality, and histopathology during acute Chagas' disease experimentally produced by inoculation of 10 or 100 bloodstream forms of Trypanosoma cruzi Y strain in susceptible mice was carried out. Parasites were searched for comparatively using three different methods: direct counting, Ficoll-MI density flotation, and hemoculture. Ficoll-MI density flotation promptly discriminated with high reproducibility subpatent parasitemic states not detected in the blood samples analyzed by direct counting. Despite the high proportion of supposedly uninfected animals and depending on the postinfection time, the majority of the mice had bloodstream parasites at the subpatent level detected by Ficoll-MI, and all of them had muscular lesions during the acute phase. All Ficoll-MI-negative blood samples from infected mice were also negative by hemoculture. Normal mouse blood purposely contaminated with parasite quantities ranging from 200 to 2000/ml was tested comparatively by density flotation and hemoculture and showed frequencies of reisolation varying from 25 to 100%. Overall, these data showed that inoculum as low as 10 infective forms of Y strain is able to induce acute Chagas' disease in susceptible mice and that a subpatent parasitemic state of 600-1000 forms/ml is a common finding. The use of Ficoll-MI to detect subpatent parasitemia is discussed. PMID- 1516672 TI - Plasmodium chabaudi: estradiol suppresses acquiring, but not once-acquired immunity. AB - This study investigates the effect of estradiol (E) on self-healing of Plasmodium chabaudi malaria in mice of the inbred strain C57BL/10. Our data show: (1) Female mice and male castrates are capable of self-healing infections when challenged with 10(6) P. chabaudi-infected erythrocytes. Self-healing is completely suppressed after pretreatment of mice with 12 micrograms E injected sc twice a week for 3 weeks. (2) The suppressive effect of E is prevented by the estrogen receptor blockers tamoxifen and clomiphene. (3) The nonsteroidal E-agonist diethylstilbestrol (DES) also suppresses self-healing. This suppressive DES effect is prevented by tamoxifen. (4) In mice immune to P. chabaudi, neither survival rate nor the course of parasitemia is affected by E, even at 10-fold higher E doses. Our data suggest that the immunosuppressive action of E is a specific genomic effect, i.e., E-induced gene products prevent the development of protective immunity against P. chabaudi. PMID- 1516673 TI - Plasmodium falciparum: release of circumsporozoite protein by sporozoites in the mosquito vector. AB - The release of circumsporozoite (CS) protein by Plasmodium falciparum sporozoites was investigated to identify factors regulating this process within infected Anopheles gambiae mosquitoes. The potential for sporozoites to release CS protein in vitro was not dependent upon their site-specific developmental stage (i.e., mature oocysts, hemolymph, salivary glands), their duration in the vector, or their exposure to mosquito-derived components such as salivary glands or hemolymph. The capacity of sporozoites to release CS protein was depressed by mosquito blood feeding during periods of sporozoite migration to the salivary glands, but the effect was only temporary and those sporozoites already in the glands were not affected. Free CS protein in the salivary glands was present in 93.3% of 45 infective mosquitoes. Sporozoites from these same, individual mosquitoes were also tested in vitro for CS protein release. In both cases, the amount of soluble CS protein increased as a function of sporozoite density but the total amount of CS protein per sporozoite became progressively less with increasing numbers of sporozoites. Further experiments showed that sporozoite contact with increasing amounts of soluble CS protein caused a down-regulation of CS protein release. Thus, a primary factor regulating the production and release of CS protein by sporozoites is their contact with soluble CS protein within the mosquito. PMID- 1516674 TI - Leishmania donovani: in vitro growth inhibition of promastigotes by a carbocyclic analog of 2'-deoxyguanosine. PMID- 1516676 TI - Effects of vitamin B12 on plasma melatonin rhythm in humans: increased light sensitivity phase-advances the circadian clock? AB - Vitamin B12 (methylcobalamin) was administered orally (3 mg/day) to 9 healthy subjects for 4 weeks. Nocturnal melatonin levels after exposure to bright light (ca. 2500 lx) were determined, as well as the levels of plasma melatonin over 24 h. The timing of sleep was also recorded. Vitamin B12 was given blind to the subjects and crossed over with placebo. We found that the 24-h melatonin rhythm was significantly phase-advanced (1.1 h) in the vitamin B12 trial as compared with that in the placebo trial. In addition, the 24-h mean of plasma melatonin level was much lower in the vitamin B12 trial than with the placebo. Furthermore, the nocturnal melatonin levels during bright light exposure were significantly lower in the vitamin B12 trial than with the placebo. On the other hand, vitamin B12 did not affect the timing of sleep. These findings raise the possibility that vitamin B12 phase-advances the human circadian rhythm by increasing the light sensitivity of the circadian clock. PMID- 1516675 TI - What's new in chitinase research? PMID- 1516677 TI - Presence of a partial urea cycle in the leech, Poecilobdella granulosa. AB - Ornithine carbamoyltransferase (OCT) and arginase, but not arginine synthetase (AS), were detected in the body wall and gut tissues of the leech. The activities of these enzymes were not altered by starvation. The high activity of arginase in body wall is probably due to the association of the latter with botryoidal tissue. Hirudineans, which evolved from oligochaete ancestors, appear to have lost the citrulline-arginine segment of the urea cycle due to their ammonotelic mode of nitrogen excretion. PMID- 1516678 TI - Do taste receptors respond to perturbation of water structure? AB - The pmr spin-spin pulse relaxation times (T2 values) of the L-amino acids are examined in relation to their taste threshold values. There is an inverse trend between T2 value and threshold value with a good correlation for amino acids whose natural pH is close to neutrality. These results may indicate that taste receptors respond to perturbation of water structure. PMID- 1516679 TI - Gastrointestinal transit and digestibility of maltitol, sucrose and sorbitol in rats: a multicompartmental model and recovery study. AB - Using data obtained with a dye marker and the gavage technique, the kinetics of gastrointestinal transit of different loads of sugar substitutes (maltitol, sorbitol) and sugar (sucrose) in the rat were analysed using a linear multicompartmental model over a range from the realistic to the non-physiologic high, of carbohydrate intake levels and using only a few experimental time points. The model gave detailed insight into intestinal propulsion and gastrocecal transit time. Rate constants of transport between the compartments investigated were determined; they showed characteristics which could be related to the substance and the dosage administered. Analyses of the gastrointestinal content and calculations of the intestinal net water movement showed that the digestibility and absorption of the disaccharide sugar alcohol, maltitol, in the small gut depended inversely on the dose ingested. For all substances tested, caloric availability in the small intestine was calculated. At a physiological low level of maltitol intake, the results also indicated an insignificant calorie saving effect in comparison to sucrose, an effect based mainly on the slow absorption rate of the maltitol cleavage product sorbitol. PMID- 1516680 TI - Deciduogenic effects of mediators of the polyphosphatidylinositol pathway in pseudopregnant mice. AB - Intraluminal injections (15 microliters) of either concanavalin A (125 micrograms) or ionophore A 23,187 (0.01 mumol) induced a decidual cell reaction (DCR) in the uterus of day 4.5 pseudopregnant mice. However, when these agents were administered in different combinations with each other or with CaCl2 (15 mumol) and phorbol-12-myristate-13-acetate (1.6 nmol), interacting effects occurred to either enhance or inhibit each of the others' independent deciduogenic capacities. The results suggest that the polyphosphatidylinositol pathway and Ca2+ are involved in the induction of the DCR in mice with complex interactions occurring between the active components of the pathway to modulate the outcome of the transformation process. PMID- 1516681 TI - Effect of monensin and diabetes on asialoglycoprotein degradation in rat hepatocytes. AB - We have studied the effects of two modulations--streptozotocin-induced diabetes in vivo, and the presence of the carboxylic proton ionophore monensin in vitro- on the degradation of 3H-asialoorosomucoid ligand in isolated rat hepatocytes. The ligand was internalized by means of a synchronous wave procedure. Diabetes was associated with a marked decrease in the amount of total degraded radioactive ligand compared to that in normal cells (3.6% and 37.3% of internalized ligand respectively, at 60 min), together with increased secretion of degradation products into the incubation medium (87% and 46.3% of the total degraded ligand was secreted by diabetic and normal cells, respectively). Monensin induced similar effects in normal cells, but had no apparent effect in diabetic cells. PMID- 1516682 TI - Carbamazepine inhibits NMDA-induced depolarizations in cortical wedges prepared from DBA/2 mice. AB - There is some doubt as to the mechanism of action of the widely-used anticonvulsant drug, carbamazepine. In cortical wedges prepared from genetically epilepsy-prone DBA/2 mice, carbamazepine at therapeutic concentrations (1-10 microM) markedly reduced the depolarization produced by N-methyl-D-aspartate (NMDA). The NMDA sub-type of glutamate receptor has been implicated in the pathogenesis of epilepsy and the inhibitory action of carbamazepine on this response suggests that the anticonvulsant action of the drug may be due to its blockade of NMDA receptor-mediated events. PMID- 1516683 TI - Phosphoramidon enhances allatostatin-mediated inhibition of juvenile hormone biosynthesis in the corpora allata of the cockroach, Diploptera punctata. AB - Use of enkephalinase inhibitor phosphoramidon in the in vitro radiochemical assay for juvenile hormone biosynthesis enhanced allatostatin-mediated inhibition of hormone production by corpora allata of the cockroach, Diploptera punctata. Significant increases in inhibition in day 2 virgin female CA by AST 1 (at 10(-7) M) and AST 4 (10(-8)-10(-7) M) were observed in the presence of phosphoramidon (10(-5) M or greater). No significant increase in inhibition were seen in CA from day 6 mated females with AST 4 (10(-9)-10(-7) M) and phosphoramidon combined. Phosphoramidon alone had no effect on JH biosynthesis. Analysis of allatostatin content of the CA, as determined by ELISA, revealed that addition of phosphoramidon to the medium increased the endogenous allatostatin content in CA of virgin and mated females. The similarity in primary structure between allatostatins and enkephalin-like peptides and their similar distribution makes it probable that phosphoramidon acts by preventing breakdown of allatostatins within the CA. PMID- 1516684 TI - Development of melatonin rhythm in the pineal gland and eyes of chick embryo. AB - A melatonin rhythm was observed in the pineals of 18-day-old chick embryos incubated under a light-dark regime of 18: 6 h. A low pineal melatonin content was found during the light phase of the day. Concentrations started to increase 2 h after dark onset and reached maximum levels after 4 h of darkness. The amplitude of the pineal melatonin rhythm increased considerably after 2 days and night-time concentrations in 20-day-old embryos were more than 5 times higher than in 18-day-old ones. Significant day/night differences in melatonin production were found both in pineals and eyes. Exposure of eggs to 1 h of light during the dark period decreased the high melatonin concentrations in the eyes but not in the pineals of the 20-day-old chick embryo. The results suggest that in this precocial bird at least part of the circadian system may already operate during embryonic life. PMID- 1516685 TI - A multivariate approach to socio-ecological development and endocrine variance in the spotted hyaena, Crocuta crocuta Erxleben. AB - This investigation of the socio-ecological development and endocrine variance in the spotted hyaena, Crocuta crocuta, illustrates that the complexity of a multivariate endocrine system cannot fully be understood using the concept of a class mean (mu). Any comprehensive investigation of a multivariate endocrine system should also include an analysis of variance (sigma), as it may provide additional insights into the dynamics of an endocrine hypervolume. Mean cortisol concentrations could not differentiate between various social and reproductive categories (MANOVA); however, in males an analysis of variance (principal component analysis) indicated that the contrast between cortisol and androstenedione was the principle axis of variance once the androgen secreting ability had been accounted for. On the other hand, the same contrast was found to be the principal axis of variance in the female sub-sample, suggesting that cortisol may play a significant role in regulating the endocrine dynamics of this species, despite showing little variance in mean values among various social and reproductive categories. PMID- 1516686 TI - Modification of the skin feeding site by tick saliva mediates virus transmission. AB - A tick vector of Thogoto (THO) virus was shown to secrete a factor in saliva which potentiates the transmission of THO virus to uninfected ticks feeding on an apparently non-viraemic host. The effect of the saliva activated transmission (SAT) factor on the virus occurred at the site of inoculation in the skin and was apparent even when the virus was introduced 3 days after the SAT factor. The results suggest that tick saliva can play an important role in disease transmission by virtue of host modification at the site of feeding. PMID- 1516687 TI - New bone induction by demineralized bone matrix in immunosuppressed rats. AB - Subcutaneous implantation of demineralized bone matrix (DBM) initiates a sequence of developmental events which culminate in endochondral bone formation. To test the effects of T-cell deficiency on new bone formation, the morphology of DBM induced bone was examined in rats thymectomized at three weeks of age and in thymectomized or nonthymectomized rats lethally irradiated and reconstituted with syngeneic bone marrow. At 24 days after implantation, bone induction in control rats was appropriate for their age, while thymectomized-irradiated-reconstituted rats and thymectomized rats had significantly more new bone and larger bone marrow space than the controls. In non-thymectomized, irradiated and reconstituted rats, bone induction occurred in only 25% of the animals, compared to 95% in other groups. PMID- 1516688 TI - Protein synthesis during germination of heterothallic yeast ascospores. AB - Protein synthesis during ascospore germination of the heterothallic Saccharomyces cerevisiae strain AP-3 was investigated. Protein synthesis in the germinating ascospores appeared to begin approximately 20 min following glucose initiation. Since RNA synthesis did not start until approximately 70 min after the onset of germination, strain AP-3 ascospores must contain RNA which is ready for immediate translation. Both trehalase and glyceraldehyde-3-phosphate dehydrogenase activities were found to be affected by the onset of germination. Trehalase activity was found to increase severalfold following 60 min of spore germination but remained relatively constant over the subsequent 120 min examined. Dehydrogenase activity was not detectable in AP-3 ascospores but was measurable in germinating ascospores. PMID- 1516689 TI - Two-state model of Paramecium bursaria thigmotaxis. AB - A theoretical framework has been developed for analysis of the interaction between Paramecium bursaria and a glass surface. Adhesion to and detachment from a solid substrate were considered in the model as transitions between alternative states in cell behavior: (a) swimming, and (b) motionless (positive thigmotactic) state. According to the model and experimental data, a change in the fraction of swimming cells is described by a negative exponential course. The proposed model allows positive thigmotaxis, generally referred to in the literature simply as thigmotaxis, to be considered as the rate-constant of transition into the motionless state. This approach permits quantitative determination of thigmotaxis, and reveals its dependence on the phase of culture growth and the type of medium surrounding the cells. In the mineral maintenance solution, paramecia from the stationary phase of growth swim more slowly than those in the logarithmic phase of growth, and show enhanced thigmotaxis. However, a general relationship between thigmotaxis and swimming speed was not established. PMID- 1516690 TI - Molecular cloning of a cDNA that encodes a serine protease with chymotryptic and collagenolytic activities in the hepatopancreas of the shrimp Penaeus vanameii (Crustacea, Decapoda). AB - Two clones were isolated by screening a shrimp hepatopancreas cDNA library with a DNA fragment obtained by PCR amplification using two oligonucleotides based on the partial protein sequence of Penaeus vanameii chymotrypsin purified earlier. One of these clones, PVC 7 contains a complete cDNA coding for a serine protease. The deduced amino acid sequence shows the existence of a 270 residue-long preproenzyme containing a highly hydrophobic signal peptide of 14 amino acids. This suggests the existence of a putative zymogen form of the enzyme containing a 30 amino acid-long peptide which is cleaved to give a mature protein of 226 residues. A highly preferred codon usage is observed for this protein. The other obtained cDNA was found to encode the less predominant variant of the protein. Sequence alignments show that shrimp chymotrypsin is highly homologous with crab collagenase (77% homology taking into account the same amino acid at the same position, and 83% homology taking into account amino acids with conserved function) and that it is more similar to mouse trypsin (41% homology of strictly conserved amino acids) than to hornet chymotrypsin (35% homology). PMID- 1516691 TI - Thermal injury and ozone stress affect soybean lipoxygenases expression. AB - The effects of thermal injury (cold and heat shock) and ozone treatment on lipoxygenases 1 (LOX-1) and 2 (LOX-2) of soybean seedlings have been investigated. Cold stress led to a decrease of the specific activities of both isoenzymes, attributable at least in part to a down-regulation of gene expression at the translational level. Both heat shock and ozone treatment enhanced lipoxygenases-specific activities, acting at the level of transcription of the genes. It is proposed that LOX-1 and LOX-2 are involved in the thermotolerance of soybeans and in the precocious aging induced by ozone. PMID- 1516692 TI - Peptidyl-prolyl cis-trans isomerase from Bacillus subtilis. A prokaryotic enzyme that is highly sensitive to cyclosporin A. AB - Cyclophylins are members of a class of proteins with peptidyl-prolyl cis-trans isomerase activity. These enzymes bind the immunosuppressive agent, cyclosporin A (CsA), which acts as a competitive inhibitor. The peptidyl-prolyl cis-trans isomerase from Bacillus subtilis (PPIase) was purified to homogeneity in a 4-step purification procedure, which resulted in a 100-fold protein purification with a yield of 5%. Coomassie blue-stained SDS-PAGE revealed a single band of about 18 kDa. PPIase activity was determined using synthetic peptides as substrates in a 2 step reaction coupled to chymotrypsin. Treatment of Bacillus subtilis PPIase by CsA revealed an inhibition constant of Ki = 175 nM, which differs from cyclophilin of enterobacteria such as E. coli or Salmonella typhimurium and is in the range of human enzymes. PMID- 1516693 TI - Influence of amphipathic peptides on the HIV-1 production in persistently infected T lymphoma cells. AB - The effects of several amphipathic peptides on HIV-1 production in persistently infected cells are described. Melittin, a 26 amino acid alpha-helical amphipathic peptide, reduces HIV-1 production dose-dependently, whereas other amphipathic peptides do not. Six melittin derivatives which retain the alpha-helical portion have similar effects as melittin. The reduction of viral infectivity is not due to an effect of melittin on the virus particles but to an intracellular action of the peptide, which is readily taken up into cells, as shown by quantitative ELISA. Western blots of cells from melittin-treated cultures suggest that the processing of the gag/pol precursor is impaired. PMID- 1516694 TI - The effect of dilauroyl-L-3-phosphatidylcholine on the interaction between cytochrome P-450 1A1 and benzo[a]pyrene. AB - Fluorescence quenching of benzo[a]pyrene (BP) by cytochrome P-450 1A1 was used to probe the effect of the lipid, dilauroyl-L-3-phosphatidylcholine, on this substrate-enzyme interaction. In the presence of lipid, a monoclonal antibody to this P-450 maximally inhibited BP binding at an antibody-to-P-450 ratio of 1:2, corresponding to an antibody crosslinked P-450 complex. The antibody did not inhibit BP binding in the absence of lipid. These results indicate that when P 450 is subjected to the orientational constraints imposed by antibody-mediated crosslinking, the lipid alters the conformation or quaternary structure of the P 450 oligomer in a manner which changes its affinity for BP. PMID- 1516695 TI - Heat and cold denaturation of beta-lactoglobulin B. AB - The thermal denaturation of bovine beta-lactoglobulin B was investigated by high sensitivity differential scanning microcalorimetry between pH 1.5 and 3.0 in 20 mM phosphate buffer. The process was found to be a reversible, two-state transition. Progressive addition of guanidine hydrochloride at pH 3.0 leads to the appearance of a low-temperature calorimetric endotherm, corresponding to the cold renaturation of the protein. Circular dichroism experiments have confirmed the low and high temperature denaturation processes, and have shown some structural differences between both denatured states of beta-lactoglobulin B. PMID- 1516696 TI - Effect of pancreatic type phospholipase A2 on isolated porcine cerebral arteries via its specific binding sites. AB - The addition of porcine pancreatic group I phospholipase A2 (PLA2-I) produced a transient contraction followed by a relaxation in helical strips of porcine cerebral arteries. Its ED50 value (2.3 nM) was almost identical to the Kd value (3.9 nM) calculated from the specific binding of 125I-labeled porcine PLA2-I in cultured porcine cerebral arterial smooth muscle cells. Type-specific action of PLA2s and homologous desensitization strongly implicated the involvement of PLA2 I-specific sites in the response. The transient contraction was abolished by treatment with indomethacin as well as by the removal of endothelium, indicating the dependence of vasoconstrictor prostaglandins synthesized by PLA2-I in endothelium. The PLA2-I-induced relaxation response was also observed in bovine and cat cerebral arteries, thus providing a new aspect of PLA2-I as a vasoactive substance. PMID- 1516697 TI - Differences in the thermostabilities of barley (1----3,1----4)-beta-glucanases are only partly determined by N-glycosylation. AB - Barley (1----3,1----4)-beta-glucan 4-glucanohydrolase (EC 3.2.1.73) isoenzyme EII carries 4% by weight carbohydrate and is more stable at elevated temperatures than isoenzyme EI, which has no associated carbohydrate. The relationship between carbohydrate content and thermostability has been investigated by treatment of the two isoenzymes with N-glycopeptidase F (EC 3.5.1.52). Removal of carbohydrate from isoenzyme EII results in a decrease in the enzyme's thermostability, but treatment of isoenzyme EI with the N-glycopeptidase F has no effect. In addition, removal of a single N-glycosylation site in isoenzyme EII (Asn190-Ala-Ser) by site-directed mutagenesis of the corresponding cDNA led to a reduction in thermostability, while the introduction of this site into isoenzyme EI enhanced stability. We conclude that N-glycosylation of Asn190 enhances the stability of isoenzyme EII at elevated temperatures, but that other factors related to their primary structures also contribute to the differences in thermostabilities of the barley (1----3,1----4)-beta-glucanases. PMID- 1516698 TI - A membrane-associated cysteine protease inhibitor from murine hepatoma. AB - A cysteine protease inhibitor was purified from total membrane fractions of an invasive murine hepatoma, Hepa cl 9. On gel filtration under non-reducing conditions the purified inhibitor was eluted in a single peak of M(r) 10-15 kDa, but resolved as two bands at 14 and 70 kDa on SDS-PAGE under reducing conditions. By isoelectric focusing, the inhibitor ran at an isoelectric point of 4.75. Immunoblotting studies using the enhanced chemiluminescence technique indicated no crossreactivity with monoclonal antibodies to stefin B and cystatin C or with a polyclonal antibody to low M(r) kininogen. In contrast, the 14 kDa and 70 kDa bands both crossreacted with a polyclonal antibody to stefin A, suggesting that the cysteine protease inhibitor associated with Hepa cl 9 membranes may be a modified form of stefin A. PMID- 1516699 TI - The primitive metazoan Hydra expresses antistasin, a serine protease inhibitor of vertebrate blood coagulation: cDNA cloning, cellular localisation and developmental regulation. AB - We have isolated and characterized cDNAs from Hydra which encode antistasin, a potent inhibitor of factor Xa in the vertebrate blood clotting cascade. Hydra antistasin is expressed in gland cells and represents a major class of transcripts from Hydra's head. Sequence analysis revealed that Hydra antistasin contains 6 internal repeats of a 25-26 amino acid sequence with a highly conserved pattern of 6 cysteine and 2 glycine residues identical to that in leech antistasin. Conservation of antistasin in a lower metazoan provides a potential link between the vertebrate and invertebrate coagulation systems. PMID- 1516700 TI - Over-expression of the small heat-shock protein, hsp25, inhibits growth of Ehrlich ascites tumor cells. AB - hsp25 is a small, growth-related, mammalian stress protein which is highly accumulated in the stationary phase of Ehrlich ascites tumor in vivo. Ehrlich ascites cells cultivated in vitro under conditions of continuous exponential growth express hsp25 only at a low level. These cells were stably transfected with an eukaryotic expression vector carrying the coding sequence of the small heat-shock protein, hsp25, under control of the murine metallothionein promoter. The resulting cell lines (EAT II6 and EAT II8) exhibit constitutive over expression of the small heat-shock protein, hsp25, which can be further increased by induction with cadmium. Both cell lines show increased thermoresistance. The in vitro proliferation rate of the transfected cell lines EAT II6 and EAT II8 is significantly decreased depending on the degree of cadmium-regulated over expression of hsp25. Furthermore, a significant delay in Ehrlich ascites tumor growth in mice using the hsp25 over-expressing cells for primary inoculation could be demonstrated. PMID- 1516701 TI - Endothelin 1 hydrolysis by rat kidney membranes. AB - Hydrolysis of endothelin 1 by rat kidney membranes was investigated using a reverse-phase HPLC and an automated gas-phase protein sequencer. Endothelin 1 was hydrolyzed into four major fragments which were detected by HPLC. Phosphoramidon, an inhibitor of neutral endopeptidase 24,11, almost completely suppressed the production of three fragments, but one fragment was not affected by the inhibitor. Analysis of N-terminal sequences of the degradation products revealed that the phosphoramidon-sensitive fragments were generated by cleavage at the Ser5-Leu6 bond of endothelin 1 that was identical with its cleavage site by purified rat endopeptidase 24,11, reported previously. The phosphoramidon insensitive fragment was produced by cleavage at Leu17-Asp18, which was distinct from the sites by endopeptidase 24,11, but corresponded to that by a phosphoramidon-insensitive metallo-endopeptidase recently isolated from rat kidney membranes by us [(1992) Eur. J. Biochem. 204, 547-552]. Kinetic determination of endothelin 1 hydrolysis by the isolated enzyme yielded values of Km = 71.5 microM and kcat = 1.49 s-1, giving a ratio of kcat/Km = 2.08 x 10(4) s 1.M-1. The Km value was much higher and the kcat/Km value was much lower than those for rat endopeptidase 24,11 reported previously. Thus, endopeptidase 24,11 appears to hydrolyze endothelin 1 more efficiently than the isolated enzyme does. Both enzymes may play physiological roles in the metabolism of endothelin 1 by rat kidney membranes in vivo. PMID- 1516702 TI - The genetic defect of the original Norwegian lecithin:cholesterol acyltransferase deficiency families. AB - Three of the original Norwegian lecithin:cholesterol acyltransferase (LCAT) deficiency families have been investigated for mutations in the gene for lecithin:cholesterol acyltransferase by DNA sequencing of the exons amplified by the polymerase chain reaction. A single T----A transversion in codon 252 in exon 6 converting Met(ATG) to Lys(AAG) was observed in all homozygotes. In spite of the identical mutation, the disease phenotypes differed in severity. This was not reflected in the expression of LCAT in the heterozygotes. PMID- 1516703 TI - Cloning and sequence analysis of a cDNA clone from Arabidopsis thaliana homologous to a proteasome alpha subunit from Drosophila. AB - A cDNA clone isolated from an Arabidopsis thaliana cell suspension culture library showed considerable similarities to the proteasome 28 kDa alpha subunit of Drosophila [(1990) Gene 90, 235-241]. The 250 amino acid-long protein encoded by Arabidopsis TAS-g64 clone has important homologies in its primary structure and in the predicted secondary structure with the PROS-28.1 clone from Drosophila. The only divergence observed between the two sequences is for the 20 C-terminal amino acids. This subunit might share important functions in both kingdoms, as revealed by the important conservation between plants and animals. In plant cells it is encoded by a single-copy gene and probably regulated by stress and/of division. PMID- 1516704 TI - The disulfide bridge pattern of snake venom disintegrins, flavoridin and echistatin. AB - Flavoridin and echistatin, isolated from the venom of Trimeresurus flavoviridis and Echis carinatus, respectively, belong to the disintegrin family of integrin beta 1 and beta 3 inhibitors of low molecular weight RGD-containing, cysteine rich peptides. Since disulfide bonds are critical for expression of biological activity, we sought to determine their location in these two proteins. In flavoridin, direct evidence for the existence of linkage between Cys4-Cys19 and between Cys45 and Cys64 was obtained by analysis of proteolytic products, and indirect evidence suggests links between Cys6-Cys14 and Cys13-Cys36. In echistatin, links between Cys8-Cys37 and Cys20-Cys39 were identified by direct chemical analysis. PMID- 1516705 TI - Influenza virus A infection induces interleukin-8 gene expression in human airway epithelial cells. AB - To determine the role of the airway epithelial cell in mediating virus-induced inflammation, we infected primary cultures of human airway epithelial cells with human influenza type A/Port Chalmers/72 (H3N2). After two days, the medium was collected for measurement of the chemotactic cytokine interleukin-8 by enzyme linked immunosorbent assay. The RNA was extracted from the cells for analysis of interleukin-8 mRNA by Northern blot analysis. Interleukin-8 production was more than doubled by viral infection, while interleukin-8 mRNA was increased four fold. Thus induction of interleukin-8 gene expression in virus-infected airway epithelium may be an important early step leading to virus-induced airway inflammation. PMID- 1516706 TI - Cell-free translation in reversed micelles. AB - Cell-free translation in reversed micelles (RM) of surfactants in organic solvents is demonstrated using as an example the synthesis of human interleukin-2 by the wheat germ translation system solubilized in Brij 96 (oleyl poly(10)oxyethylene ether) RM in cyclohexane. The translation system components and the product were recovered from the RM system by acetone precipitation. The recovery and translation reaction yields depended on the degree of surfactant hydration. The translation yields in Brij 96 RM were close to that observed in regular aqueous solution. The Brij 96 RM system is regarded as a promising media for the cell-free synthesis of hydrophobic proteins. Meanwhile, no translation reaction was observed in Aerosol OT (sodium bis(2-ethylhexyl) sulfosuccinate) RM in octane, which presumably is due to the ability of Aerosol OT to bind Mg2+ ions necessary for the functioning of the translation apparatus. PMID- 1516707 TI - Carbohydrates in mammalian tryptophanyl-tRNA synthetase. AB - Homogeneous preparations of bovine tryptophanyl-tRNA synthetase (EC 6.1.1.2) contain monosaccharides (mannose, fucose, galactose, N-acetylglucosamine) as revealed by liquid chromatography. Their content comprises 2.5-3.0% (w/w) of the enzyme composed of two subunits (60 kDa x 2). The same set of sugars was detected in elastase and CNBr-generated fragments (with molecular masses of approx. 40 kDa and 30 kDa, respectively). It is concluded that bovine tryptophanyl-tRNA synthetase, in addition to being a metallo- and phosphoprotein, is also a glycoprotein. PMID- 1516708 TI - Isolation from Spirulina membranes of two photosystem I-type complexes, one of which contains chlorophyll responsible for the 77 K fluorescence band at 760 nm. AB - Two types of chlorophyll-protein complexes of photosystem I (PSIa, PSIc) have been isolated from the membranes of Spirulina platensis using a Triton X-100 treatment and chromatography on DEAE-Toyopearl. The complexes are equally enriched with P700 (Chl: P700 = 100-110) but show different electrophoretic molecular masses--140 (PSIa) and 320 kDa (PSIc)--and differ in the content of long-wavelength absorbing Chl. PSIa has a typical PSI fluorescence band at 730 nm (F730) as the main band at 77 K, whereas PSIc is responsible for F760, the intensity of which depends on the redox state of P700. PSIc only shows 77 K light induced variable fluorescence at 760 typical of Spirulina membranes and cells. PMID- 1516709 TI - Direct RNA polymerase chain reaction for TMV detection in crude cell extracts. AB - A part of the 30,000 bp transport protein gene of tobacco mosaic virus (TMV) RNA was amplified via direct RNA PCR and via traditional reverse transcription followed by cDNA PCR. Both amplified cDNA products were restricted with NcoI or HaeIII endonucleases and identical restriction fragments were produced. Two efficient methods of viral RNA concentration from an infected tobacco leaf extract were used: both 3-3.5 M sodium acetate alone and 3 M LiCl with 4 M urea quantitatively precipitated TMV RNA from the extracts. TMV RNA thus obtained could be readily amplified by direct RNA PCR. These results demonstrate that direct RNA PCR can be applied for the detection or/and analysis of high molecular weight RNA and for diagnosis of viral infections. PMID- 1516710 TI - Leukotriene A4 hydrolase, a bifunctional enzyme. Distinction of leukotriene A4 hydrolase and aminopeptidase activities by site-directed mutagenesis at Glu-297. AB - We previously obtained evidence for intrinsic aminopeptidase activity for leukotriene (LT)A4 hydrolase, an enzyme characterized to specifically catalyse the hydrolysis of LTA4 to LTB4, a chemotactic compound. From a sequence homology search between LTA4 hydrolase and several aminopeptidases, it became clear that they share a putative active site for known aminopeptidases and a zinc binding domain. Thus, Glu-297 of LTA4 hydrolase is a candidate for the active site of its aminopeptidase activity, while His-296, His-300 and Glu-319 appear to constitute a zinc binding site. To determine whether or not this putative active site is also essential to LTA4 hydrolase activity, site-directed mutagenesis experiments were carried out. Glu-297 was mutated into 4 different amino acids. The mutant E297Q (Glu changed to Gln) conserved LTA4 hydrolase activity but showed little aminopeptidase activity. Other mutants at Glu-297 (E297A, E297D and E297K) showed markedly reduced amounts of both activities. It is thus proposed that either a glutamic or glutamine moiety at 297 is required for full LTA4 hydrolase activity, while the free carboxylic acid of glutamic acid is essential for aminopeptidase. PMID- 1516711 TI - Studies on antisense inhibition of translation in vitro. Anomalies and re evaluation. AB - Experiments were carried out to better characterize antisense control of translation. Results in an E. coli system confirmed specific inhibition of poly(U) translation. At low concentrations, certain homopolymers (including poly(rA)) stimulated translation. Oligo(dA(n)) was inhibitory at n less than or equal to 8. Translation of globin mRNA in reticulocyte lysates indicated that ssDNA 15-mers targeted at beta-globin mRNA inhibited both alpha- and beta-globin production. Sequences targeted immediately downstream of the AUG were the least effective in inhibition. These and other anomalies are discussed here in relation to those of others, emphasizing caution in performing antisense experiments. PMID- 1516712 TI - Carboxyl-terminal processing may be essential for production of active NiFe hydrogenase in Azotobacter vinelandii. AB - The NiFe hydrogenase from Azotobacter vinelandii is a membrane-bound alpha beta heterodimer that can oxidize H2 to protons and electrons and thereby provide energy. Genes encoding the alpha and beta subunits, hoxG and hoxK respectively, followed by thirteen contiguous accessory genes potentially involved in H2 oxidation, have been previously sequenced. Mutations in some of these accessory genes give rise to inactive enzyme containing an alpha subunit with decreased electrophoretic mobility. Mass spectral analysis of the subunits demonstrated that the alpha subunit had a molecular weight 1,663 Da less than that predicted from hoxG. Since the N-terminal sequence of the purified alpha subunit matches the sequence predicted from hoxG we suggest this difference is due to removal of the C-terminus of the alpha subunit which may be an important step linked to metal insertion, localization, and formation of active hydrogenase. PMID- 1516713 TI - Protein conformational changes and myelin solubilization by anion-detergent solutions. AB - The addition of sodium sulfate to a myelin suspension in sodium phosphate buffer at neutral pH, containing octyl glucoside detergent (OG), increases the membrane solubility more than 5-fold by an unknown structural mechanism. FTIR spectroscopy has been applied to investigate anion effects on the conformational structure of myelin proteins. Sulfate and sulfate-phosphate media, but not phosphate alone, induce a great conformational protein disorder. The addition of the detergent to the anion mixture solution prevents the myelin from protein denaturation. The conformational transitions have also been quantified through the amide I region. Explanations of these changes and their connections with myelin solubility are also included. PMID- 1516714 TI - A selective inhibitor of cyclic AMP-dependent protein kinase, N-[2 bromocinnamyl(amino)ethyl]-5-isoquinolinesulfonamide (H-89), inhibits phosphatidylcholine biosynthesis in HeLa cells. AB - In this study, we report that the potent and selective inhibitor of cyclic AMP dependent protein kinase, N-[2-bromocinnamyl(amino)ethyl]-5 isoquinolinesulfonamide (H-89) interferes with the incorporation of choline into phosphatidylcholine in HeLa cells. Treatment of cells with 10 microM H-89 for 1 h decreases the phosphatidylcholine biosynthesis by 50%. This inhibition is prevented by simultaneous addition of 10 microM forskolin, while the choline uptake itself is not affected by H-89. PMID- 1516715 TI - Synthesis of a large peptide mimicking the DNA binding properties of the sex determining protein, SRY. AB - The sex determining protein, SRY, has been recently described as containing a DNA binding motif, also called the SRY box. This 80 amino acid box was synthesized using the continuous flow solid-phase technique. The product was then purified and tested according to such diverse criteria as its intrinsic structure or its biological activity (DNA binding capacity), and compared to the full-length protein. The data indicate that the peptide is relevant for the properties described so far for the protein. PMID- 1516716 TI - Mono ADP-ribosylation of transducin catalyzed by rod outer segment extract. AB - Transducin is the retinal rod outer segment (ROS)-specific G protein coupling the photoexcited rhodopsin to cyclic GMP-phosphodiesterase. The alpha subunit of transducin is known to be ADP-ribosylated by bacterial toxins. We investigated the possibility that transducin is modified in vitro by an endogenous ADP ribosyltransferase activity. By using either ROS, cytosolic extract of ROS or purified transducin in the presence of [alpha-32P]nicotinamide adenine dinucleotide (NAD+), the alpha and beta subunits of transducin were found to be radiolabeled. The labeling was decreased by snake venom phosphodiesterase I (PDE I). The modification was shown to be mono ADP-ribosylation by analyses on thin layer chromatography of the PDE I-hydrolyzed products which revealed only 5'AMP residues. In addition we report that sodium nitroprusside activates the ADP ribosylation of transducin. PMID- 1516717 TI - Synthesis of active metabolite(s) from 1 alpha-hydroxyvitamin D3 by human monocytic leukemia cells. AB - Synthesis of the biologically active metabolite(s) from 1 alpha-hydroxyvitamin D3 (1 alpha(OH)D3) was examined in various types of human leukemia cell lines. Untreated monocytoid leukemia cells (U937 and HEL/S) metabolized 1 alpha (OH)D3 to the active metabolite(s), possibly 1 alpha, 24- and/or 1 alpha, 25 dihydroxyvitamin D3, and these cells were efficiently induced to differentiate by treatment with 1 alpha (OH)D3. However, the other types of leukemia cells did not efficiently metabolize it and were not induced to differentiate by 1 alpha (OH)D3. The possible therapeutic advantage of 1 alpha (OH)D3 in the treatment of monocytic leukemia is discussed. PMID- 1516718 TI - Expression of protein kinase C subspecies in rat retina. AB - An extract of rat retina was subjected to Mono Q followed by chromatography on hydroxyapatite, and the protein kinase C (PKC) subspecies were identified by immunoblot and biochemical analysis. It was found that, although the relative activities assayed with myelin basic protein as a common phosphate acceptor vary greatly with one another, the alpha-, beta I-, beta II-, gamma-, delta-, epsilon , zeta-, and another structurally unknown PKC subspecies are expressed in this tissue. Thus, the retina is a unique tissue which expresses most of the PKC subspecies so far identified in mammals. PMID- 1516719 TI - Molecular cloning and expression of the human melanocyte stimulating hormone receptor cDNA. AB - Melanocytes and melanoma cells are known to possess receptors for melanocyte stimulating hormone (MSH). A cDNA clone, designated 11D, has been isolated from human melanoma cells and encodes a MSH receptor. The cloned cDNA encodes a 317 amino acid protein with transmembrane topography characteristics of a G-protein coupled receptor, but it does not show striking similarity to already published sequences of other G-protein-coupled receptors. When 11D cDNA is expressed in COS 7 cells, it binds an 125I-labelled MSH analogue (NDP-MSH) in a specific manner. The bound ligand could be displaced by melanotropic peptides, alpha-MSH, beta MSH, gamma-MSH and ACTH (adrenocorticotropic hormone), but not by the non melanotropic peptide, beta-endorphin. This is the first report of the cloning of the receptor gene of the melanotropin receptor family. PMID- 1516720 TI - [11 beta-hydroxysteroid dehydrogenase and steroid receptors]. AB - 11 beta-Hydroxysteroid dehydrogenase (11 beta-HSD), as its name implies, is the enzyme responsible for the conversion of cortisol to cortisone, and of corticosterone to 11-dehydrocorticosterone. Ulick et al. reported the detailed investigation of a patient with the syndrome of apparent mineralocorticoid excess (AME), who had the stigmata of florid hyperaldosteronism but low normal or suppressed levels of renin and aldosterone. Such patients show marked abnormalities of cortisol metabolism. From a series of studies, the consensus grew that AME reflects the absence, or very low activity, of 11 beta-HSD in the kidney of affected patients. In addition to providing a framework for understanding the pathogenesis of AME, these studies prompted a re-evaluation of other areas of steroid in the kidney. Glycyrrhetinic acid, the active principle of liquorice and carbenoxolone, exerted its mineralocorticoid action not by a direct effect on mineralocorticoid receptors but by inhibiting renal 11 beta-HSD, thus producing a mild, drug-induced form of AME. Recently Monder et al. reported the cloning and expression of rat and human cDNA encoding corticosteroid 11 beta dehydrogenase. The physiological role of 11 beta-HSD in conferring aldosterone selectivity on otherwise non-selective type I receptors has been focused using the genetic method in addition to the biological ones. PMID- 1516721 TI - [Diagnostic imaging of the thyroid]. AB - Among various imaging modalities used for the diagnosis of thyroid diseases, ultrasonography is the most sensitive and economical method to visualize anatomic detail and structural relations. Scintigraphy using 123I or 99mTc gives critical information about thyroid cell function and makes it possible to differentiate the causes of thyrotoxicosis. Tumor scintigraphy using 201T1, 67Ga, 131I metaiodobenzyl guanidine or 99mTc(V)-dimercaptosuccinic acid is useful for the characterization of nodules. Recently introduced magnetic resonance imaging appears promising in demonstrating pseudocapsules around tumors and capsular invasion. PMID- 1516722 TI - [A case of pseudohypoparathyroidism (PHP) type II associated with Bartter's syndrome--restoration of phosphaturic response to parathyroid hormone (PTH) by treatment for hypopotassemia]. AB - We report a case of PHP Type II whose phosphaturic response to PTH was restored by treatment for complicated Bartter's syndrome. A 34-year-old woman was admitted to our hospital in July 1990 because of tetanic convulsion. The physical examination showed normal blood pressure (118/62mmHg), round face without shortness of metacarpal bones and positive Trousseau's sign. Although renal function was normal, hypocalcemia (6.5mg/dl) and hyperphosphatemia (4.8mg/dl) in association with high levels of serum PTH (942pg/ml) and 1.25 (OH)2D3 (86pg/ml) were disclosed. Ellsworth-Howard test revealed that there was no increase in the urinary secretion of phosphate despite an increase in urinary cAMP excretion. On the other hand, hypopotassemia (2.5mEq/l) and metabolic alkalosis with high plasma renin activity (22.8ng/ml/hr) and aldosterone concentration (22.7ng/dl) were coexistent. Pressor response to angiotensin II infusion was blunted. Although no glomeruli were obtained by renal biopsy specimen, vacuolar degeneration on proximal tubules were noted. These findings indicated that she had PHP Type II associated with Bartter's syndrome. By administration of potassium (24mEq/day), spironolactone (50mg/day) and only small doses of 1 alpha hydroxyvitamin D3 (0.5mg/day), serum levels of potassium as well as calcium were normalized and tetanic attacks disappeared. In March 1991, she was re-examined by Ellsworth-Howard test in order to clarify the effects of hypopotassemia on renal tubular response to PTH. Interestingly, phosphaturic response to PTH was restored, and the degree of increase in urinary cAMP excretion was 4 times as high as that on the first admission. These results suggest that hypopotassemia changes the response of renal proximal tubular cells to PTH, particularly such as reabsorption of phosphate and cAMP response, although it is possible that hypocalcemia may contribute to the blunted phosphaturic response to PTH. The mechanism of hypocalcemia seen in this case remains to be elucidated. PMID- 1516723 TI - [Measurement IGF-I in human blood by immunoenzymometric assay]. AB - Insulin-like growth factor-I (IGF-I) is the growth factor which binds to its specific binding proteins in plasma and mediates most of the actions of growth hormone (GH). In terms of this, measurement of IGF-I concentrations is considered to be important in the diagnosis and treatment of growth abnormalities. In the present report we describe a modified immunoenzymometric assay (IEMA) for IGF-I using monoclonal antibody and peroxidase conjugated polyclonal antibody, which was originally developed by Tamura et al. The minimum detection level was 3ng/ml and good linearity was obtained at a range of 3-50ng/ml. The recovery of added IGF-I was nearly quantitative, and cross reaction with human IGF-II was less than 1%. There was a significant positive correlation between the IGF-I values determined by IEMA and by RIA. We measured the levels of IGF-I by this IEMA in normal subjects and children with short stature. Serum or plasma samples were extracted by acid-ethanol method. In normal children IGF-I level was observed age dependently. IGF-I values gradually increased and reached peak levels (101.2 473.2ng/ml) in pubertal period and thereafter decreased to adult levels (67.3 329.6ng/ml). In subjects with short stature older than 5 yrs, the percentages falling below the normal mean for chronological age by at least 2SD were 100% for complete GH deficiency (n = 5), 80.0% for partial GH deficiency (n = 15), 25.0% for GH neurosecretory dysfunction (n = 4), 40.0% for non-endocrine short stature (n = 60) and 25.0% for Turner syndrome (n = 4). In children younger than 4 yrs, it may be difficult to use IGF-I for diagnosis of GH deficiency because there was an overlap in IGF-I values with normal children. IEMA for IGF-I is shown to be a reliable method for measurement of IGF-I in blood and is appropriate for diagnosis of growth disorders with short stature in subjects older than 5 yrs. PMID- 1516724 TI - [The role of insulin on renal sodium handling and sympathetic nerve activity in overweight normotensive subjects]. AB - Recently, it was suggested that the role of hyperinsulinemia on the hypertensive mechanism of essential hypertension might be related to renal sodium handling and sympathetic nerve activity, especially in obese hypertensive patients. However, the interrelationship between insulin, obesity, renal sodium metabolism and sympathetic nerve activity in normotensive subjects (NT) still remains unclear. The present study, therefore, was undertaken to clarify the role of insulin on renal sodium handling and sympatho-adrenal function in overweight NT. The study consisted of 24NT, who were divided into two groups of twelve non-obese (NNT) and twelve obese (ONT) subjects. NNT was categorized as a body mass index (BMI) less than, and ONT as a BMI equal to or more than 25kg/m2. In the early morning, after overnight fasting, all subjects remained in a supine state and were examined for renal clearance test. During the two-hour clearance period, mean arterial pressure (MAP), heart rate (HR), endogenous creatinine clearance(CCr), urinary excretion of sodium (UNaV), fractional excretion of sodium (FENa), plasma immunoreactive insulin (IRI), plasma norepinephrine concentration (pNE), and plasma epinephrine concentration (pE) were determined. Although no significant difference was found in age, MAP, HR, pE, CCr or UNaV between the two groups, a significantly higher IRI (p less than 0.05) and lower FENa (p less than 0.05) were observed in ONT than in NNT. There was no significant correlation between IRI and UNaV, FENa or pE in ONT or in NNT. In addition, no significant correlation was shown between FENa and pNE or pE in both groups.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1516725 TI - Interaction of phospholipids with proteins and peptides. New advances 1990. AB - 1. The review deals with the recent achievements in the study of the various interactions of phospholipids with proteins and peptides. 2. The interactions are classified according to the hydrophobic, hydrophilic or mixed character of the interactive forces. 3. The effect of the interaction on the structure and biological activity of the interacting molecules is also discussed. PMID- 1516726 TI - Enzymic degradation of alginates. PMID- 1516727 TI - Patterns of sulphation in heparan sulphate: polymorphism based on a common structural theme. AB - HS appears to be a well-organised molecule with a domain structure that is apparently unique amongst the GAG family (Gallagher, 1989). Further refinements in sequence analysis are needed to corroborate the simplified model proposed in Fig. 4. It is still not clear why evolution has favoured a structural motif of widely spaced sulphated domains. Presumably, some advantages must accrue to the organism from this design, and one idea, that we have discussed previously, is that the polysaccharide functions as a "template" for the organisation of structural proteins in the ECM and for the binding and presentation of growth factors within the matrix polymer network. The sulphated regions are likely to display considerable conformational versatility as a result of the presence of the iduronate residues, and this property may be very important for the protein binding properties of the polysaccharides (Casu et al., 1988). Sulphation patterns within these regions could favour oligosaccharide conformations necessary for specific protein interactions. An important question in this context is why different cells express on their surfaces HS with subtle differences in sulphation pattern. Perhaps the polymorphic features of HS are involved in higher-order tissue- and organ-specific mechanisms controlling cellular recognition and morphogenesis. The consistency with which aberrant sulphation of HS is detected in malignant disease (Gallagher and Lyon, 1989) in which cellular recognition and differentiation are impaired, adds some substance to this view. PMID- 1516728 TI - Glutathione depletion and rabbit renal medulla 6-ketoPGF1 alpha and TxB2: levels in vivo and following homogenate incubation in vitro. AB - 1. The effect of glutathione (GSH) depletion on rabbit renal medullary homogenate 6-ketoPGF1 alpha and TxB2 synthesizing capability was investigated. 2. GSH depletion in vivo with diethyl maleate (DEM) produced higher (P less than 0.05) 6 ketoPGF1 alpha and TxB2 renal medullary levels compared to controls. Homogenization and incubation lowered (P less than 0.05) GSH such that there were no differences in GSH between treatments after 5 min of incubation. By 30 min, GSH was lower (P less than 0.05) and 6-ketoPGF1 alpha higher (P less than 0.05) in homogenates from controls in comparison to those from DEM-treated rabbits. 3. The results indicate GSH depletion increased 6-ketoPGF1 alpha levels in rabbit renal medulla in vivo but subsequent GSH catabolism prevented assessing the effect of this GSH depletion on prostanoid synthesizing capability. PMID- 1516729 TI - Use of mitochondrial inner membrane proteins and phospholipids to facilitate disengagement of the catalytic and malonyl-CoA binding components of carnitine palmitoyltransferase from liver mitochondrial outer membranes. AB - 1. It was shown by Ghadiminejad and Saggerson (1991) that the anionic detergent cholate caused disengagement of the malonyl-CoA binding entity from the catalytic entity of outer membrane carnitine palmitoyltransferase (CPT1). 2. This disengagement was only observed if inner membrane material was present. 3. It is now shown that this effect is mimicked by a CPT-free inner membrane protein fraction together with an inner membrane lipid extract or with individual phospholipids (phosphatidylcholine, phosphatidylethanolamine or diphosphatidylglycerol). 4. The lipids alone have no effect but act synergistically with the inner membrane protein fraction. PMID- 1516730 TI - Analysis of the conformation and stability of human bronchial lysozyme by circular dichroism. AB - 1. Human bronchial lysozyme was isolated from nonpurulent secretions and studied by circular dichroism (CD) spectroscopy for its conformational properties. 2. The two negative bands at 208 and 222 nm indicated that the peptide chain adopted an alpha-helical structure in physiological conditions. 3. The molecule was stable at pH 1.0 but not at pH 12.0. 4. Increasing ionic strength by adding NaCl up to 1 M did not change the CD spectra. 5. Complete unfolding of the molecule by guanidinium chloride was obtained only at the concentration of 6 M. 6. Bronchial lysozyme was also denatured by sodium dodecyl sulphate. 7. The molecule was stable when mild reduction was performed at 37 degrees C for 30 min but was completely unfolded after heating at 100 degrees C for 3 min. PMID- 1516731 TI - Characterization of polyclonal antibodies against ovine adipocyte plasma membranes. AB - 1. Antisera against ovine adipocyte plasma membranes were developed in a mare. 2. These antisera showed a high degree of specificity to adipocyte plasma membranes and cross-reacted with other tissues. 3. Antisera cross-reactivity can be removed by adsorption of the antiserum with various tissue plasma membranes without significant reduction in their reactivity to adipocyte plasma membranes. 4. Antisera reacted with different affinity to adipocyte plasma membranes from different sites and from different species of animals. PMID- 1516732 TI - Stabilization of porcine spleen cathepsin A with chaotropic ions and its destabilization with thiols at intralysosomal pH. AB - 1. A correct assay for cathepsin A was developed by adding 0.1 M NaNO3 as an enzyme stabilizer to the assay system. 2. Cathepsin A was purified homogeneously from porcine spleen by DE 52 column, Sephadex G-150 column and Try-Phe-CH Sepharose column chromatography. 3. The optimum pH of the cathepsin A activity was 4.9, which is near the value of the intralysosomal pH. 4. Chaotropic agents exerted stabilizing effects on the purified cathepsin A activity at pH 5.0, with sodium nitrate being the most effective among the agents tested. 5. Cathepsin A was inactivated rapidly and irreversibly by thiols. PMID- 1516733 TI - Polyoxyethylene 9-lauryl ether-solubilized alkaline phosphatase: synergistic stimulation by zinc and magnesium ions. AB - 1. Polidocanol-solubilized apoalkaline phosphatase could be stimulated either by zinc ions (Kd = 8.5 nM) or by magnesium ions alone (Kd = 3.8 microM). 2. Zinc and magnesium ions had synergistic effects on Polidocanol-solubilized apoalkaline phosphatase, leading to a fully active enzyme (700-800 U/mg). 3. Zinc ions inhibited non-competitively the Polidocanol-solubilized apoenzyme (Ki = 7.1 microM) by displacing magnesium ions from their binding sites. 4. A model for the action of zinc and magnesium ions on the modulation of the enzyme activity is proposed. PMID- 1516734 TI - Investigation of the presence of branched-chain alpha-keto acid dehydrogenase in mammalian hepatic peroxisomes. AB - 1. Rat liver was fractionated into peroxisomes and mitochondria and branched chain keto acid (BCKA) dehydrogenase activity was measured. 2. All BCKA dehydrogenase activity was associated with the mitochondrial fraction and none with the peroxisomal fraction. 3. BCKA dehydrogenase was also not detected in hepatic peroxisomes of rats treated with clofibrate which induces several peroxisomal enzymes. 4. Hepatic peroxisomes from rabbit, hamster and dog also did not show any BCKA dehydrogenase activity. 5. We conclude that mammalian hepatic peroxisomes do not contain BCKA dehydrogenase. PMID- 1516735 TI - Reactivation of denatured citrate synthase. AB - 1. The imported mitochondrial enzyme citrate synthase can be partially (less than or equal to 45%) reactivated after denaturation in guanidinium chloride, if the concentration of the denaturing agent is lowered by dialysis, rather than by dilution, when essentially no reactivation is observed. 2. The presence of a reducing agent (dithiothreitol) is necessary for regain of activity. 3. Optimum regain of activity occurs at enzyme concentrations of about 10-20 micrograms/ml; at higher concentrations there is significant formation of aggregates. PMID- 1516736 TI - Regulating effect of mitochondrial lactate dehydrogenase on oxidation of cytoplasmic NADH via an "external" pathway in skeletal muscle mitochondria. AB - 1. The specific activity of lactate dehydrogenase of skeletal muscle mitochondria was found to be 2.5 times lower than specific activity of total NADH-cytochrome c reductase. 2. The specific activity of mitochondrial LDH in skeletal muscle mitochondria was almost equal to the activity of rotenone-insensitive NADH cytochrome c reductase. 3. Mitochondrial LDH acting as an oxidase of lactate to pyruvate may feed an "external" pathway, but the activity of the mitochondrial enzyme is a limiting factor in oxidation of lactate-derived NADH. 4. Mitochondrial LDH acting as a reductase of pyruvate to lactate successfully competes with an "external" pathway for cytoplasmic NADH. 5. Exogenous NADH oxidation via an "external" pathway was inhibited by pyruvic acid. This inhibition was overcome by addition of oxamic acid or hydrazine. PMID- 1516737 TI - Tyrosylprotein sulfotransferase in rat submandibular salivary glands. AB - 1. The transfer of sulfate ester group from 3'-phosphoadenosine 5'-phosphosulfate (PAPS) to poly-(Glu6, Ala3, Tyr1) (EAY; Mr 47 kDa) in rat submandibular salivary gland has been investigated. The highest tyrosylprotein sulfotransferase activity was obtained in the Golgi-enriched fraction in the presence of 2 mM 5'AMP, 20 mM MnCl2 and 50 mM NaF at pH 6.2. 2. The apparent Km values for EAY and PAPS were 1.6 x 10(-6) and 1.9 x 10(-6) M, respectively. 3. Inclusion of NaCl, EDTA, NEM and DTT was inhibitory for the enzyme activity. The enzyme was 28 times less susceptible to 2,6-dichloro-4-nitrophenol inhibition than to phenol sulfotransferase inhibition. 4. This study is the first report characterizing a sulfotransferase activity specific for tyrosylprotein in rat submandibular salivary glands. PMID- 1516738 TI - Enzyme studies on human and snail beta-mannosidase using a fluorescence assay and an HPLC/diode array method with Man beta (1-4)GlcNAc as substrate. AB - 1. Snail beta-mannosidase showed a Km value of 0.05 mM toward MU-beta-Man and could not be inhibited by Man, GlcNAc, Man beta(1-4)GlcNAc, Man beta(1-4)GlcNAc beta(1-N)urea or Man beta(1-4) GlcNAc beta(1-4)GlcNAc. 2. The Km value of the snail enzyme towards Man beta(1-4)GlcNAc, as measured by HPLC, was 10 mM, explaining the lack of inhibition. 3. The Km value of the human serum beta mannosidase towards MU-beta-Man was 0.3 mM, but the human enzyme was not capable of degrading Man beta(1-4)GlcNAc in detectable amounts. PMID- 1516739 TI - On the role of rat liver cytosol in suppression of low-level chemiluminescence during nonenzymatic lipid peroxidation. AB - 1. The effect of normal rat liver cytosol on the level of Fe/ADP-ascorbate induced lipid peroxidation in the total particulate fraction (mitochondria plus microsomes) has been studied. The intensity of lipid peroxidation was measured using chemiluminescence technique and malondialdehyde (MDA) formation. 2. Dialysed cytosol significantly decreased the level of chemiluminescence, and to a much lesser extent, the rate of MDA production. 3. Gel filtration on a Sephadex G 200 column led to appearance of at least three cytosolic fractions which suppressed the low-level chemiluminescence. 4. The discovered components differed from each other by their molecular masses, kinetics of chemiluminescence inhibition and effects on intensity of MDA formation. 5. The putative functional role of antioxidative defence factors from rat liver cytosol is discussed. PMID- 1516740 TI - Control of the cell cycle. AB - Cell division is arguably the most fundamental developmental process for single celled and multicellular organisms alike. The pathway from one cell division to the next is known as the cell cycle. A conserved biochemical regulatory network controls progress along this pathway in plants, animals, and yeasts. This review is intended to serve as a primer on the current state of the eukaryotic cell cycle regulatory model, an introduction to the special roles of cell division and its control in plant development, and a review of recent progress in applying the universal mitotic control paradigm to higher plant systems. PMID- 1516741 TI - The 29-kDa hemocyte proteinase dissociates fat body at metamorphosis of Sarcophaga. AB - Previously, we reported the purification of a 29-kDa proteinase from the pupal hemocytes of Sarcophaga peregrina (flesh fly). Antibody against this proteinase was found to inhibit dissociation of the fat body by pupal hemocytes in vitro. Moreover, the purified enzyme alone was shown to dissociate the fat body. This enzyme was found to be localized in granules of heterogeneous size in the hemocytes and to be released on their interaction with the fat body. From these results, we conclude that this 29-kDa proteinase participates in dissociation of the fat body at metamorphosis. PMID- 1516742 TI - Mesenchyme of embryonic reproductive ducts directs process outgrowth of Retzius neurons in the medicinal leech. AB - In the two segments of the medicinal leech (Hirudo medicinalis) that contain the male (segment 5) and the female (segment 6) reproductive ducts, the paired Retzius (Rz) neurons are distinguished by several unique properties. For example, the muscles and glands of the body wall are the primary peripheral targets of Rz neurons in standard segments [Rz(X)], whereas the muscles and glands of the reproductive ducts are the primary peripheral targets of Rz neurons in the two reproductive segments [Rz(5,6)]. In this paper, we show that organogenesis and differentiation, which generate an epithelial tube surrounded by mesenchymal cells, occur in the embryonic reproductive ducts at approximately the time when Rz processes first contact these structures. The growth cones leading one branch of the posterior axon of Rz(5,6) contact the duct mesenchymal cells. Following initiation of this contact, these posterior growth cones enlarge and send out numerous filopodia. Secondarily, growth cones leading the anterior axon of each Rz(5,6) also modify their shapes and trajectories. When embryonic reproductive ducts were transplanted into posterior (nonreproductive) segments, the branch of the posterior Rz axon near the ectopic reproductive tissue produced enlarged growth cones and extended several secondary branches into the mesenchyme of the ectopic tissue. This result suggests that the reproductive mesenchyme is attractive to, and can modify the growth of, all Rz neurons. The behavior of Rz(5,6) growth cones suggests that the reproductive mesenchyme cells provide guidance cues that control the location in which Rz axons elaborate their peripheral arborization and form synapses, and that the mesenchyme may also stimulate the production of a densely branched arbor. PMID- 1516743 TI - Structure and expression of the Xenopus retinoblastoma gene. AB - We have cloned a Xenopus homology (XRb1) of the human retinoblastoma susceptibility gene. DNA sequence analysis shows that the XRb1 gene product is highly conserved in many regions. The leucine repeat motif and many of the potential cdc2 phosphorylation sites, as well as potential sites for other kinases, are retained. The region of the protein homologous to the SV40 T antigen binding site and the basic region directly C-terminal to the E1A binding site are all conserved. XRb1 gene expression at the RNA level was studied by Northern blot analysis. Transcripts of 4.2 and 10-kb are present as maternal RNA stores in the oocyte. While the 4.2-kb product is stable until at least the mid-blastula stage, the 10-kb transcript is selectively degraded. Between stages 11 and 13 the 10-kb transcript reappears and also a minor product of approximately 11 kb becomes apparent. Both the 4.2- and the 10-kb transcripts remain present until later stages of development and are also present in all adult tissues examined, although at differing levels. Antibodies raised against human p105Rb which recognize the protein product of the XRb1 gene, pXRb1, detect the Xenopus 99-kDa protein prior to the mid-blastula stage, but at lower levels than at later stages in development. PMID- 1516744 TI - Characterization of RNA polymerase II-dependent transcription in Xenopus extracts. AB - We examine the RNA polymerase II-dependent transcription directed by several promoters in extracts prepared from distinct developmental stages of Xenopus laevis. RNA polymerase II accurately initiates transcription from the cytomegalovirus, herpes simplex virus thymidine kinase, and Xenopus heat-shock protein (hsp) 70 promoters. The efficiency of transcription of these different promoters is dependent on whether extracts from oocytes, eggs, or somatic cells are used and on the temperature of incubation. In contrast to the viral promoters, the hsp 70 promoter is more active at heat shock temperatures in oocyte and egg extracts (31 degrees-34 degrees C) than at physiological temperatures for Xenopus (20 degrees-25 degrees C). These in vitro transcription extracts should be useful in examining the molecular mechanisms responsible for differential gene expression during Xenopus development. PMID- 1516745 TI - Transient increase in expression of a glutamate decarboxylase (GAD) mRNA during the postnatal development of the rat striatum. AB - We recently reported that the mammalian brain has two forms of the GABA synthetic enzyme glutamate decarboxylase (GAD, E.C. 4.1.1.15), which are the products of two genes. The two forms, which we call GAD65 and GAD67, differ from each other in sequence, molecular size, subcellular distribution, and interactions with the cofactor pyridoxal phosphate (PLP), with GAD65 activity more dependent than that of GAD67 on the continued presence of exogenous PLP. The existence of two GAD genes suggests that individual GABA neurons may be subject to differential regulation of GABA production. We have examined the expression of these two forms of GAD during postnatal development of the rat striatum to determine whether different classes of GABA neurons selectively express different amounts of the two GAD mRNAs. Here we present evidence for a dramatic developmental difference in the expression of the two mRNAs during postnatal development of the rat striatum. Using in situ hybridization to the two GAD mRNAs, we observed a selective increase in GAD65 mRNA during the second postnatal week, at the time when striatal matrix neurons innervate the substantia nigra (SN). PLP-dependent enzyme activity in the midbrain increases in parallel with increased expression of GAD65 mRNA in the striatum. We hypothesize that the innervation of the SN by striatal neurons triggers an increase in GAD65. The changing ratios of GAD65 and GAD67 in the striatum may contribute to the well-documented changes in seizure susceptibility that occur in early life. PMID- 1516746 TI - Roles for the extracellular matrix in plant development and pollination: a special case of cell movement in plants. AB - Pattern formation in plants is now thought to be primarily dependent on positional information during development. We discuss the prevalent theories on how position is deciphered by cells in an organism and highlight the recent advances implicating molecules of the cell wall or extracellular matrix (ECM) in this process. We compare the functions of the ECM in plants and animals and describe the various cell and substrate adhesion molecules of the animal ECM which play a role in morphogenesis and cell movement. We propose that analogous molecules may occur in plants and provide evidence for the presence of a substrate adhesion molecule like vitronectin in plants and algae. We provide a model for how substrate adhesion molecules may be involved in a special case of cell movement in plants, pollination. PMID- 1516747 TI - Evidence that metalloendoproteases are involved in gamete fusion of Ciona intestinalis, ascidia. AB - The use of specific inhibitors and substrates of metalloendoproteases provides evidence that in many systems these enzymes are involved in membrane fusion events. In this study, we investigated whether metalloendoproteases are involved in Ciona sperm-egg fusion. In vitro fertilization assays with the metal chelator 1,10-phenanthroline, specific metalloendoprotease substrates, and the vital stain Hoechst 33342 suggested that a Zn(2+)-dependent metalloendoprotease(s) takes part in Ciona sperm-egg fusion. Furthermore, electrophysiological recordings showed that insemination carried out in the presence of either 1,10-phenanthroline or the substrate CBZ-Gly-Phe-NH2 fails to induce fertilization potential or any other change in membrane potential. These results support the hypothesis that in Ciona intestinalis, a metalloendoprotease(s) is functional in gamete fusion. PMID- 1516748 TI - Differential regulation of the transforming growth factor type-beta 2 gene promoter in embryonal carcinoma cells and their differentiated cells. AB - Previous studies have shown that EC cells do not express detectable levels of TGF beta 2 or its mRNA until they differentiate. This suggested that differentiation influences the transcription of the TGF-beta 2 gene in this model system. To address this possibility, we have examined the activity of the TGF-beta 2 promoter in EC cells and their differentiated cells using gene constructs containing various portions of the TGF-beta 2 promoter inserted upstream of the reporter gene, chloramphenicol acetyltransferase (CAT). We determined that the level of CAT increases approximately ninefold when EC cells were induced to differentiate. Our studies also indicate that the TGF-beta 2 promoter contains at least two positive regulatory elements that are separated by a negative regulatory element. Finally, we have identified a CRE/ATF-like site that appears to be responsible for a positive regulatory element located between -77 and -40. PMID- 1516749 TI - The maryland mammoth allele and rooting both perturb the fate of florally determined apices in Nicotiana tabacum. AB - The stability of the florally determined state in terminal and axillary buds of two tobacco cultivars was studied. We used Hicks and Hicks Maryland Mammoth, near isogenic cultivars of Nicotiana tabacum differing at the recessive maryland mammoth locus which confers short-day behavior. The experimental design consisted of growing plants in short-day conditions and subjecting them to three bioassays in long-day conditions: in vitro culture of apices consisting of meristems and three to four leaf primordia; rooting of buds consisting of meristems and 8 to 12 leaves, leaf primordia, and internodes; and release from apical dominance of axillary buds in situ. Cultured terminal and axillary apices expressed floral determination, indicating that meristems can be florally determined. Two lines of evidence indicate that rooting destabilizes an already acquired florally determined state: cultured apices from both axillary and terminal buds produced fewer nodes after excision than homologous buds which were rooted; and a lower percentage of rooted axillary buds from Hicks Maryland Mammoth plants expressed floral determination than did homologous axillary buds grown out in situ in noninductive conditions. Rooted buds from the two genotypes expressed floral determination at different frequencies, but produced abnormal inflorescences at similar frequencies, indicating that roots and the maryland mammoth allele influence common as well as unique processes associated with floral determination. PMID- 1516750 TI - Biophysical mechanisms for morphogenetic progressions at the shoot apex. AB - Leaf primordia, first visible as small bumps, are produced in a cyclical pattern at the edges of the shoot apex, a smooth region at the top of the stem. Their formation is a biomechanical process. This review first considers hypothetical construction mechanisms and then summarizes research that provides information about how and where the primordia are made. Studies of growth at the primordium site indicate the importance of growth parallel to the surface in generating the forces for primordium emergence. The symmetry of the pattern of reinforcement by cellulose microfibrils correlates with the subsequent pattern of primordium production. Finite element models of the apex reveal that lateral bulging of the apex results in a gradient of shear stress, with high shear at the future primordium site. In contrast, tension parallel to the surface is lowest at the primordium site. Response of apical surface tissue to punctures indicates that an existing primordium can exert a pulling force tangential to its base and a compressive force perpendicular to its base. These observations lead to identification of a continuous biophysical cycle for apex morphogenesis, in which most of the steps are direct physical consequences of the previous step. Biophysical processes, subject to input from genetic, hormonal, and environmental sources, are thus involved in the construction and patterning of leaf primordia. PMID- 1516751 TI - A conceptual framework for maize leaf development. AB - What is and is not known about the maize leaf is reviewed. Analysis of genetic mosaics and direct observation with the SEM have broken leaf development into three distinct phases: recruitment of cells within the meristem, cell division into the 0.6-mm tall primordium, and postprimordial division and differentiation into the mature leaf. New data are presented that imply that cell division rates in the leaf are coordinated by inductive signals from the internal cells. Leaf cells that tend to divide more are held in check by slower growing neighbors; this complicates the search for developmental compartments. Experiments with recessive mutants that remove the ligule and auricle have been important in identifying an inducer signal with the specific meaning "make ligule-auricle." We have studied many dominant mutant alleles at seven different genes. Each mutant alters the position of the ligule boundary. We conclude the following. First, the mutants act in particular domains of the primordium. Second, the dominant mutants all move the ligule boundary in the same direction. Third, the mutants all retard developmental stage transitions. Fourth, three and probably four of the seven genes for which dominant mutants have been studied specify homeodomain proteins in the wrong place. The concept of "maturation schedule" is used to explain these data. All of the dominant mutant phenotypes are seen as consequences of immature cells being in the wrong place when inductive signals pass through the leaf. Several specific questions of leaf development and especially questions as to source of inductive signals or homologies among juvenile and adult organ parts are recast in light of this "maturation schedule" hypothesis. PMID- 1516752 TI - Development states associated with the floral transition. AB - Floral initiation can be analyzed from a developmental perspective by focusing upon how developmental fates are imprinted, remembered, and expressed. This is not an altogether new perspective, since people studying flowering have been concerned for a long time with the commitment of meristems to form flowers and the morphological, cellular, and molecular changes associated with this commitment. What is novel is the emphasis on developmental states as opposed to physiological processes. This developmental focus indicates that there appear to be at least three major developmental states that are acquired and expressed in the process of a meristem initiating floral morphogenesis. The meristem cells must first become competent to respond to a developmental signal that evokes them into a florally determined state. The leaves are the usual source of this signal and a specific leaf may or may not have the capacity to be inductively active. When a leaf does develop the capacity for inductive activity, this capacity is usually correlated with the ontogeny of the leaf. Inductive activity, however, may be continually expressed as in some day-neutral plants or may be latent as in plants where the photoperiod is the external cue for activity. Competent shoot apical meristems respond to inductive leaf signal by being evoked into a florally determined state. Under permissive conditions this florally determined state is expressed as the initiation of floral morphogenesis. Many mechanisms have evolved to regulate entry into and expression of these developmental states. As we learn more about the developmental states associated with flowering and how they are acquired and expressed, we will understand better how the various patterns of flowering are related to one another as well as which developmental processes are common to all angiosperms. PMID- 1516753 TI - Cell-cell communication in plants: self-incompatibility in flower development. AB - Self-incompatibility, a mechanism that prevents self-fertilization in plants, is based on the ability of the pistil to discern the presence of self-pollen and on the female tissue's capacity to inhibit the growth or germination of self related, but not of genetically unrelated, pollen. As a self-recognition system, self-incompatibility responds to specific cellular products and signals and thus offers a unique system in which to study the components of cellular communication in plants. The cytological manifestations of self-incompatibility have been well studied, and, with the cloning of cDNAs for several proteins associated with this recognition process, a detailed molecular view of self-incompatibility is emerging. PMID- 1516754 TI - Mammalian sperm-egg fusion: the rat egg has complementary sites for a sperm protein that mediates gamete fusion. AB - Rat epididymal protein DE is localized on the fusogenic region of the acrosome reacted spermatozoa and has a potential role in sperm-egg fusion. We investigated the presence of DE binding sites on the egg surface by co-incubating zona-free eggs and capacitated sperm in different concentrations of pure DE. Results indicate that DE produced a concentration-dependent decrease in egg penetration by sperm (fusion), with almost complete inhibition at 200 micrograms/ml. This inhibition was not due to an effect of DE on initial sperm binding to the egg membrane, since the presence of this protein did not affect the percentage of oocytes with bound sperm nor the number of bound sperm per egg. Those sperm that failed to penetrate the egg in the presence of DE became able to do so after transfer of the eggs to protein- and sperm-free medium, indicating a role for DE in an event subsequent to binding and leading to fusion. Indirect immunofluorescence using a polyclonal antibody against DE revealed a patchy labeling over the entire egg surface, with the exception of the area overlying the second metaphase spindle. This conclusion was supported by the disappearance of the DE-negative area on the fertilized egg. Zona-free eggs, incubated with DE at 4 degrees C or fixed before exposure to DE, displayed a uniform staining, suggesting that the patchy labeling resulted from aggregation of DE binding sites by the purified protein. The aggregation of these egg components may represent a necessary step of the fusion process. To our knowledge, this is the first study reporting the existence and localization of complementary sites to a specific sperm protein on the plasma membrane of the mammalian egg. PMID- 1516755 TI - Patterning the zebrafish heart tube: acquisition of anteroposterior polarity. AB - The patterning of an internal organ, like the heart, is little understood. Central to this patterning is the formation, or the acquisition, of an anteroposterior (A-P) axis. We have approached the question of how the heart tube acquires polarity in the zebrafish, Brachydanio rerio, which offers numerous advantages for studying cardiac morphogenesis. During the early stages of organogenesis in the fish, the heart tube lies in an A-P orientation with the venous end lying anteriorly and the arterial end lying posteriorly. High doses (10(-6)-10(-5)M) of retinoic acid (RA) cause truncation of the body axis, as they do in Xenopus. Low doses of retinoic acid (10(-8)-10(-7) M), which do not appear to affect the rest of the embryo, have pronounced effects upon heart tube morphogenesis, causing it to shrink progressively along the A-P axis. To investigate this further, we identified monoclonal antibodies that distinguish between the zebrafish cardiac chambers and used them to show that the RA-induced cardiac truncation always begins at the arterial end of the heart tube. There is a continuous gradient of sensitivity from the arterial to the venous end, such that increasing RA exposure causes the progressive and sequential deletion first of the bulbus arteriosus and then, in order, of the ventricle, the atrium, and the sinus venosus. As exposure increases, parts of chambers are deleted before entire chambers; thus, the sensitivity to RA appears to be independent of chamber boundaries. The analysis of the heart tube's sensitivity to RA and its timing suggest that polarity is established during or shortly after initial commitment to the cardiac lineage. PMID- 1516756 TI - Islet amyloid polypeptide--a novel controversy in diabetes research. PMID- 1516757 TI - Expression of the brain-type glucose transporter is restricted to brain and neuronal cells in mice. AB - Northern blot analysis of human tissues has demonstrated the expression of the brain-type glucose transporter isoform (GLUT 3) in liver, muscle and fat, raising the possibility that this transporter isoform may play a role in the regulation of glucose disposal in these tissues in response to insulin. We have raised an anti-peptide antibody against the C-terminal 13 amino acids of the murine homologue of this transporter isoform, and determined its tissue distribution in mouse tissues and murine-derived cell lines. The antibodies recognise a glycoprotein of about 50 kilodaltons, expressed at high levels in murine brain. In contrast to human tissues, the expression of GLUT 3 in mice is restricted to the brain, and no immunoreactivity was observed in either liver, fat or muscle membranes, or in murine 3T3-L1 fibroblasts or adipocytes. In contrast, high levels of expression of this isoform were observed in the NG 108 neuroblastoma x glioma cell line, a hybrid cell derived from rat glioma and mouse neuroblastoma cells. Taken together, these data suggest that the expression of GLUT 3 in rodents is restricted to non-insulin responsive neuronal cells and hence it is likely that the factors regulating the expression of this transporter in rodents differ to those in humans. PMID- 1516758 TI - The contribution of hyperglycaemia and hypoinsulinaemia to the insulin resistance of streptozotocin-diabetic rats. AB - The relative contribution of hyperglycaemia and hypoinsulinaemia was evaluated in rats made diabetic by streptozotocin administration. Four groups of rats were studied: untreated normal rats; streptozotocin-diabetic; streptozotocin-diabetic treated with phlorizin (0.4 mg/kg body weight per day); streptozotocin-diabetic mildly treated with insulin (0.7 IU/day). In all groups, insulin action (responsiveness) was assessed with the euglycaemic (5.3 mmol/l) hyperinsulinaemic (524 mU/l) clamp technique combined with 3H-2-deoxy-D-glucose method, enabling determination of the glucose utilization index in various tissues. Responsiveness of the overall glucose utilization process to insulin was reduced by 28% in streptozotocin-diabetic rats (12.0 +/- 1.2 vs 16.5 +/- 0.6 mg.kg-1.min-1, p less than 0.001). This was associated with a significant reduction (p less than 0.05) in the glucose utilization index in all muscles studied (average = 17.0 vs 32.1 ng.mg of tissue-1.min-1), in the heart (19.6 vs 39.5 ng.mg-1.min-1), brown adipose tissue (98.9 vs 178.0 ng.mg-1.min-1), skin (6.4 vs 13.1 ng.mg-1.min-1). Phlorizin treatment normalized plasma glucose levels without affecting those of insulin, and restored overall glucose utilization to normal (16.6 +/- 1.0 mg.kg 1.min-1). This normalization was accompanied by a normalization of the glucose utilization index in all muscle types studied (29.2 ng.mg-1.min-1), in the heart (50.0 ng.mg-1.min-1), brown adipose tissue (157.2 ng.mg-1.min-1), and skin (10.0 ng.mg-1.min-1). White adipose tissue, brain and gut were not affected.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1516759 TI - Immunocytochemical localization of heat-shock protein 60-related protein in beta cell secretory granules and its altered distribution in non-obese diabetic mice. AB - Immuno-electron microscopy technique was employed to investigate the cellular distribution of 60 kDa heat-shock protein (HSP60) in pancreatic Beta cells of control and non-obese diabetic mice. In thin sections prepared from control mice, antibody to mammalian HSP60 cross-reacted with protein(s) located to mitochondria and secretory granules. In particular, prominent binding of the antibody was seen to the insulin core of the mature insulin-secreting granules. In comparison, very little immunoreactivity was observed with immature secretory granules or with the Golgi apparatus. No binding to secretory granules or mitochondria was observed with normal mouse serum or with unrelated sera. On Western blots, HSP60 antibody specifically interacted with a single 62 kDa islet cell protein. These results suggest the existence of an HSP60-related protein with a novel location in mature secretory granules of Beta cells. The preferential association of the HSP60 related protein with the insulin core was gradually lost in Beta cells of pre diabetic non-obese diabetic mice, and correlated with the progression of insulitis. The decrease in the granular binding of the HSP60 antibody was accompanied by an increase in cytoplasm staining, and was concomitant with a significant expansion of the insulin core diameter. The altered distribution of the HSP60-related protein in prediabetic mice, together with our observation that immature secretory granules accumulate in these animals indicate that the presence of HSP60-related protein in secretory granules might be associated with the secretory function of Beta cells. PMID- 1516760 TI - Long-term suppression of postprandial hyperglycaemia with acarbose retards the development of neuropathies in the BB/W-rat. AB - The effect of the alpha-glucosidase inhibitor acarbose on postprandial hyperglycaemia was explored in the spontaneously diabetic BB/W-rat. Acarbose treatment (5 mg.kg body weight-1.day-1) of diabetic BB/W-rats maintained on small doses of insulin, was associated with a 40% reduction in the 24-h glucose area compared to non-treated diabetic rats. Over a 4 month treatment period this reduction in cumulative hyperglycaemia resulted in a complete prevention of autonomic polyneuropathy as indicated by R-BAR values. The development of somatic polyneuropathy in the BB/W-rat was significantly attenuated by acarbose treatment with a partial prevention of the characteristic nerve conduction velocity slowing during the first 3 months of diabetes, but no longer at 4 months. Characteristic structural abnormalities associated with diabetes in this model, such as axonal atrophy and axo-glial dysjunction, were significantly but only partially prevented in rats treated with acarbose for a diabetes duration of 4 months. These data suggest that postprandial lowering of hyperglycaemia resulting in a decrease in cumulative hyperglycaemia retards the development of diabetic polyneuropathies in the BB/W-rat. PMID- 1516762 TI - Habitual physical activity, aerobic capacity and metabolic control in patients with newly-diagnosed type 2 (non-insulin-dependent) diabetes mellitus: effect of 1-year diet and exercise intervention. AB - The aim of this study was to assess the effects of a 1-year intensified diet and exercise education regimen on habitual physical activity and aerobic capacity in middle-aged, obese patients with newly-diagnosed Type 2 (non-insulin-dependent) diabetes mellitus. In addition, we analysed whether the level and the changes in physical activity and aerobic capacity are related to the metabolic control of diabetes. After a 3-month basic education programme, 78 patients (45 men, 33 women) were randomly placed in an intervention or conventionally treated group. The intervention group received intensified diet education and continuous encouragement to increase physical activity which was monitored using exercise records and questionnaires. Aerobic capacity was assessed by measuring oxygen uptake at anaerobic threshold and at peak exercise. The proportion of patients with regular recreational exercise increased from 24% to 38% in the intervention men (0.10 less than p less than 0.20), remained at 54% in the conventionally treated men, increased from 53% to 70% in the intervention women (0.10 less than p less than 0.20) and from 31% to 50% (0.10 less than p less than 0.20) in the conventionally treated women. No measurable improvement was found in oxygen uptake in any of the groups. When the groups were combined, HbA1c showed an inverse correlation with oxygen uptake at anaerobic threshold (r = 0.27, p less than 0.01) and maximum oxygen uptake (r = 0.28, p less than 0.01) at 12 months.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1516761 TI - Repetitive in vivo treatment with human recombinant interleukin-1 beta modifies beta-cell function in normal rats. AB - It is unknown whether interleukin-1 exerts a bimodal effect on Beta-cell function in vivo, and whether interleukin-1 has a diabetogenic action in normal animals. We therefore studied: (a) acute effects 2 h after an intraperitoneal bolus injection of 4 micrograms of recombinant human interleukin-1 beta per kg body weight on blood glucose, plasma levels of insulin, glucagon and corticosterone in Wistar Kyoto rats, either untreated or pre-treated with 4 micrograms/kg of interleukin-1 daily for 3 or 5 days; (b) the cumulative effects of repetitive intraperitoneal injections of 4 micrograms/kg interleukin-1 on blood glucose, glucose tolerance, plasma levels of insulin, glucagon and corticosterone, pancreatic insulin content and pancreatic ultrastructure; and (c) blood glucose and plasma concentrations of insulin, glucagon and corticosterone 10 h after the last of five intraperitoneal injections of interleukin-1, at which time point the inhibitory effect of short-term interleukin-1 exposure on insulin secretion reaches its nadir in vitro. A single injection of 4 micrograms/kg of interleukin 1 caused a slight, but significant lowering of blood glucose 2 h after interleukin-1 injection with no significant changes in plasma insulin and in spite of increases in plasma glucagon and corticosterone. A lowering of blood glucose 2 h after interleukin-1 administration was reproduced with 40, but not 0.4 micrograms/kg of interleukin-1, and was also seen in interleukin-1 pre treated rats. Two hours after the fifth injection of interleukin-1, intraperitoneal glucose tolerance was impaired with elevated plasma insulin and corticosterone levels and increased pancreatic insulin content, indicating a state of insulin resistance.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1516763 TI - Metabolism of HDL apolipoprotein A-I and A-II in type 1 (insulin-dependent) diabetes mellitus. AB - Concentrations of HDL cholesterol and apolipoprotein A-I are commonly increased in Type 1 (insulin-dependent) diabetes mellitus but the mechanisms whereby diabetes influences HDL metabolism have not been studied. We investigated the metabolism of HDL apoproteins A-I and II in normolipidaemic Type 1 diabetic men (n = 17, HbA1 6.4-11.9%) without microalbuminuria but with a wide range of HDL cholesterol (0.85-2.10 mmol/l) and in nondiabetic men (n = 18) matched for body mass index and the range of HDL cholesterol. Input rates and fractional catabolic rates for apolipoproteins A-I and II were determined following injection of 125I apolipoprotein A-I and 131I-apolipoprotein A-II tracers. Additional multicompartmental analysis was performed using a model to describe the kinetics of HDL particles containing only apolipoprotein A-I (Lp A-I) and apolipoprotein A I and apolipoprotein A-II (Lp A-I/A-II). No gross differences from normal subjects were observed in the mean levels of lipids, lipoproteins, apoproteins and the lipolytic enzymes in the diabetic men as a result of the selection process. Furthermore, the relationship between apolipoprotein A kinetics and plasma HDL cholesterol levels appeared to be preserved in the diabetic group. However, some normal interrelationships were disrupted in the diabetic men. Firstly, the rate of apolipoprotein A-II synthesis was 22% lower than in control subjects (p less than 0.05). Modelling indicated that this was due to decreased input of Lp A-I/A-II particles whereas the input of Lp A-I particles was similar in the two groups. Secondly, there was no correlation between VLDL triglyceride and HDL cholesterol or VLDL triglyceride and the fractional catabolic rate of apolipoproteins A-I and A-II in diabetic men in contrast to that seen in control subjects. We conclude that there is a disruption in the normal association between VLDL and HDL metabolism in Type 1 diabetic men and postulate that the observed differences may be due to the therapeutic use of exogenous insulin. PMID- 1516764 TI - Short-term regulation of insulin-mediated glucose utilization in four-day fasted human volunteers: role of amino acid availability. AB - Glucose homeostasis in men fasted for 84 h was assessed using isotopes, indirect calorimetry and forearm balance techniques during a basal period and three sequential hyperinsulinaemic euglycaemic clamps each lasting for 150 min. Two protocols (n = 12 in each) were used: subjects were either allowed to develop hypoaminoacidaemia or received a commercial solution of L-amino acids while maintaining near-basal plasma leucine levels. Insulin infusions resulted in 3-, 35- and 650-fold increases in plasma insulin levels in both protocols. The infusion of amino acids produced a rightward shift in the dose-response curve of insulin's effect on suppressing hepatic glucose production, indicating decreased sensitivity in addition to blunting of the maximal responsiveness. Total body glucose rate of disappearance was progressively increased with escalating insulin doses, but was 22% lower at the intermediate and highest insulin doses in the group that was infused with amino acids (3.44 +/- 0.53 vs 4.82 +/- 0.71 and 7.72 +/- 1.01 vs 10.36 +/- 1.08 mg.kg-1.min-1, respectively; p less than 0.05). Forearm balance data confirmed the isotopic data, since amino acid infusions blunted the insulin-mediated increase in net forearm glucose utilization (by 50 83%). Furthermore, the infusion of amino acids resulted in marked reductions in the rate of carbohydrate oxidation and storage as assessed by indirect calorimetry. The data indicate that the amino acid-mediated suppression of glucose utilization and carbohydrate oxidation is exerted on the responsive component of insulin action. PMID- 1516765 TI - Dexamethasone treatment fails to increase arginine-induced insulin release in healthy subjects with low insulin response. AB - We have compared insulin responses to L-arginine before and during dexamethasone treatment in healthy subjects, previously classified as subjects with either high or low insulin response according to a standardized glucose infusion test. Arginine stimulation was administered as a 150 mg/kg bolus followed by 10 mg.kg 1.min-1 to six subjects with high insulin response and to seven subjects with low insulin response. Before dexamethasone treatment the incremental insulin level during 0-10 min of arginine was higher in subjects with high (36.5 +/- 6.8 microU/ml) than in subjects with low response (14.5 +/- 2.3 microU/ml), p less than 0.01 for difference. Dexamethasone treatment (6 mg/day for 60 h) markedly enhanced the insulin response to arginine in subjects with high response (+99% 0 30 min) but failed to affect the subjects with low response (+4% 0-30 min). The C peptide response to arginine exhibited similar differences between groups. Decreased responsiveness to arginine in subjects with low insulin response, especially during dexamethasone treatment, suggests a Beta-cell capacity defect although a decreased potentiating-sensing effect of glucose cannot be completely ruled out. PMID- 1516766 TI - Absence of the dawn phenomenon and abnormal lipolysis in type 1 (insulin dependent) diabetic patients with chronic growth hormone deficiency. AB - To determine the role of growth hormone in overnight insulin requirements and lipolysis, five patients with chronic growth hormone deficiency and Type 1 (insulin-dependent) diabetes mellitus and six control patients with diabetes were each studied on two separate nights. Insulin was infused at a variable rate throughout one night to maintain euglycaemia and fixed at 04.00 hours on another. During the variable infusion, euglycaemia was maintained in control patients by a 36% increase in insulin infusion rate between 03.00 and 08.00 hours while a 46% decrease in the rate was required in growth hormone deficient patients (p less than 0.02). Despite this difference, mean free insulin values were equivalent. This finding is suggestive of increased insulin clearance in growth hormone sufficient patients. Glucose levels rose in control and fell in growth hormone deficient patients when insulin infusion rates were fixed at 04.00 hours. Glycerol production and non-esterified fatty acid concentrations were significantly lower in the growth hormone deficient diabetic patients, p less than 0.001, and when normalized with a heparin infusion, had no effect on insulin requirements. We conclude that: (1) growth hormone contributes to the development of the "dawn phenomenon," possibly by increasing insulin clearance (2) growth hormone helps sustain nocturnal lipolysis in Type 1 diabetes and (3) non esterified fatty acids are not involved in the dawn phenomenon. PMID- 1516767 TI - Binding of antibodies in sera from Type 1 (insulin-dependent) diabetic patients to glutamate decarboxylase from rat tissues. Evidence for antigenic and non antigenic forms of the enzyme. AB - An islet protein of M(r) 64000, identified as the gamma-amino butyric acid (GABA) synthesizing enzyme, glutamate decarboxylase, is a major target for antibodies in Type 1 (insulin-dependent) diabetes mellitus. This enzyme is also expressed in brain and in some other tissues and may exist in multiple forms. The aim of this study was to determine the ability of antibodies from diabetic patients to recognize glutamate decarboxylase from rat islets, brain and other normal rat tissues. Glutamate decarboxylase was detected at high activity levels in brain and at lower levels in islets, kidney, liver, pituitary gland, thyroid gland, adrenal gland, testis and ovary. The ability of antibodies in sera of diabetic patients to immunoprecipitate enzyme activity from detergent extracts of tissues was determined. Antibodies in sera from diabetic patients were found to bind the enzyme from islet and brain extracts, but bound less than 20% of the activity from other tissues. The ability of antibodies to immunoprecipitate the brain enzyme was significantly correlated with the presence of antibodies to the islet 64 kilodalton antigen. These studies show that the glutamate decarboxylase activity expressed in brain shares antigenic determinants with the islet 64 kilodalton antigen. Isoforms of the enzyme expressed in other non-neuronal tissues may be antigenically distinct and may lack determinants recognized by diabetes-associated antibodies. PMID- 1516768 TI - Distinct cytoplasmic islet cell antibodies with different risks for type 1 (insulin-dependent) diabetes mellitus. AB - The cytoplasmic islet cell antibody patterns of sera from islet cell antibody positive non-diabetic and diabetic endocrine autoimmune patients, and newly diagnosed Type 1 (insulin-dependent) diabetic patients were characterised using four layer immunofluorescence with monoclonal anti-proinsulin or anti-glucagon antibodies. Two distinct islet cell antibody types were identified. One gave a diffuse cytoplasmic staining in both Beta and Alpha cells ('whole' islet pattern), and was not affected by pre-incubation with rat brain homogenate. The other had a granular appearance with staining restricted predominantly to Beta cells ('selective' islet pattern) and was completely inhibited by pre-incubation with rat brain homogenate. Some sera appeared to have a 'mixed' islet pattern, in which glucagon-positive cells gave a weaker cytoplasmic staining than proinsulin positive cells. The granular 'selective' pattern was found in sera from 19 (79%) of 24 non-diabetic endocrine autoimmune patients, in two (22%) endocrine autoimmune patients who developed Type 1 diabetes (p less than 0.0001 vs non diabetic endocrine autoimmune patients), and in none of 19 newly-diagnosed diabetic patients. The 'whole' islet pattern was found only in sera from patients who had, or who subsequently progressed to, Type 1 diabetes. This study has identified a novel islet cell antibody specificity and demonstrates that in islet cell antibody positive endocrine autoimmune patients, only islet cell antibodies which stain both Beta and Alpha cells are associated with progression to Type 1 diabetes. PMID- 1516770 TI - Intranasal glucagon in the treatment of hypoglycaemic attacks in children: experience at a summer camp. PMID- 1516769 TI - Pathogenesis of type 2 (non-insulin dependent) diabetes mellitus: a balanced overview. PMID- 1516771 TI - Hepatocarcinogenicity of chloral hydrate, 2-chloroacetaldehyde, and dichloroacetic acid in the male B6C3F1 mouse. AB - The chlorinated acetaldehydes, chloral hydrate (CH) and 2-chloroacetaldehyde (CAA), have been identified as chlorination by-products in finished drinking water supplies. Although both chemicals are genotoxic, their potential for carcinogenicity had not been adequately explored. The studies reported here are chronic bioassays conducted with male B6C3F1 mice exposed to levels of 1 g/liter CH and 0.1 g/liter CAA via the drinking water for 104 weeks. Distilled water (H2O) served as the untreated control and dichloroacetic acid (DCA; 0.5 g/liter), another chlorine disinfection by-product, was included. The mean daily ingested doses were approximately 166 mg/kg/day for CH, 17 mg/kg/day for CAA, and 93 mg/kg/day for DCA. Evaluations included mortality, body weight, organ weights, gross pathology, and histopathology. The primary target organ was the liver as the organ weights and pathological changes in the other organs (spleen, kidneys, and testes) were comparable between the treated groups and the H2O control group. Liver weights were increased for all three test chemicals at the terminal euthanasia with the greatest increase seen in the CH and DCA groups. Hepatocellular necrosis was induced by all three test chemicals, and it was also most prevalent and severe in the CH and DCA groups. A significant increase in the prevalence of liver tumors was seen for all three chemicals. The strongest response was with DCA, in which 63% of the 104-week survivors had hepatocellular carcinomas (carcinomas) and 42% possessed hepatocellular adenomas (adenomas) and the combined prevalence for carcinomas plus adenoma was 75%. The corresponding prevalence rate for carcinomas, adenomas, and combined tumors were 46, 29, and 71%; 31, 8, and 38%; and 10, 5, and 15% for CH, CAA, and H2O, respectively. In addition to the tumors we evaluated the prevalence of a possible preneoplastic lesion, the hepatocellular hyperplastic nodule (nodules), a lesion which occurred in all three treated groups but not in the H2O group. PMID- 1516772 TI - Prechronic inhalation toxicity studies of isobutyl nitrite. AB - Isobutyl nitrite (IBN) is a volatile liquid that has become increasingly popular as an inhaled recreational drug. To investigate short-term toxic effects and establish exposure parameters for chronic inhalation studies, F344/N rats and B6C3F1 mice were exposed to IBN vapors on a 6 hr/day + t90, 5 days/week schedule. Twelve exposures were administered at concentrations of 0, 100, 200, 400, 600, and 800 ppm IBN. This exposure series resulted in mortality in rats exposed to greater than or equal to 600 ppm and mice exposed to 800 ppm. Animals exposed at the lower concentrations developed hyperplasia of the bronchiolar and nasal turbinate epithelium (rats and mice) and lymphocytic atrophy in the spleen and thymus (mice). Longer term, 13-week, subchronic exposures were conducted at concentrations of 0, 10, 25, 75, 150, and 300 ppm IBN. Exposure to 300 ppm IBN reduced the body weight gains in both sexes of rats and in female mice. IBN related clinical pathology changes included reduced RBC counts accompanied by moderate increases in mean corpuscular volume and reticulocyte counts, increased WBC counts, and mildly increased methemoglobin concentration. Bone marrow hyperplasia was observed in all groups of IBN-exposed rats, while in mice only females at greater than or equal to 150 ppm IBN displayed this change. Excessive splenic pulp hematopoiesis was noted in mice at all IBN exposure levels.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1516774 TI - Assessment of a short-term reproductive and developmental toxicity screen. AB - Short-term tests for reproductive and developmental toxicity are needed to provide preliminary data on the toxicity of chemicals about which little or no data exist. An ideal design would test all aspects of reproduction and identify the target process in a short time period. One potential design has been evaluated using four chemicals of varying reproductive/developmental toxicity. Swiss mice were mated for 3 days prior to chemical exposure to produce time-mated females for gestational exposure and to ascertain fertility of the untreated males. The group of time-mated females was treated during Gestation Days 8-14 and allowed to litter for observations through Postnatal Day (PND) 4. Endpoints observed included pup number and body weights on PND 0, 1, and 4 and number of uterine implantation sites on PND 4. A second group of females was dosed daily for 19 days. After 7 days, these females (n = 10/group) were cohabited with male mice who had been treated for 5 days prior to this second mating. Daily chemical dosing continued during the 5-day cohabitation. This second group of females was killed after 19 days of treatment and the number of live and dead fetuses and implantation sites was recorded. After 17 days of dosing, male mice were killed and the reproductive system evaluated by organ weights, total epididymal sperm counts and motility, and testicular histology. All four chemicals tested, boric acid, ethylene glycol, ethylene glycol monomethyl ether, and theophylline, were found to be toxic to development or reproduction when tested previously by conventional developmental toxicity or continuous breeding protocols. This short term (21 day) design correctly identified three of these four chemicals as reproductive and developmental toxicants and distinguished the potent toxicants from the less effective compounds. This design can be used to prioritize chemicals for further study, or to delineate the relative toxicities of structurally related chemicals, and to identify the proper dose range for subsequent toxicity studies. PMID- 1516773 TI - The developmental toxicity of 2-ethylhexanol applied dermally to pregnant Fischer 344 rats. AB - Undiluted 2-ethylhexanol (2-EH) was administered by occluded dermal application for 6 hr per day on Gestation Days 6 through 15 to pregnant Fischer 344 rats, in range-finding (R) and main (M) studies. The dermal route is considered to be the most relevant for human exposure. Treatment levels were (R) 0.0, 0.5, 1.0, 2.0, and 3.0 ml/kg/day (equivalent to 0, 420, 840, 1680, and 2520 mg/kg/day) and (M) 0.0, 0.3, 1.0, and 3.0 ml/kg/day (equivalent to 0, 252, 840, and 2520 mg/kg/day). Controls (0.0 ml/kg/day, sham controls) received deionized water at 3.0 ml/kg/day. Dermal-positive control groups received undiluted 2-methoxyethanol (2 ME) at (R) 0.5 and 1.5 ml/kg/day and (M) 1.0 ml/kg/day as a reference compound in a similar regimen. An oral reference compound, valproic acid, was administered by gavage in the range-finding study on Gestation Days 6 through 15 at 400 mg/kg/day. The range-finding study employed an untreated (naive) control group. Numbers of plug-positive females per group were (R) 8 and (M) 25. Maternal weight gain was reduced for 2-EH at 1680 (R) and 2520 (R and M studies) mg/kg/day. Exfoliation and encrustation were seen at the application site in both studies at 840, 1680, and 2520 mg/kg. Maternal liver, kidney, thymus, spleen, adrenal, and uterine weights, and gestational and fetal parameters were unaffected by treatment with 2-EH. There were no treatment-related increases in the incidence of individual or pooled external, visceral, and skeletal malformations or variations following the application of 2-EH. The NOAELs for the maternal toxicity of 2-EH were 252 mg/kg/day based on skin irritation and 840 mg/kg/day based on systemic toxicity. The developmental toxicity NOAEL was at least 2520 mg/kg/day, with no teratogenicity. Administration of 2-ME at 840 mg/kg/day resulted in reduced maternal weight gain and food consumption, increased postimplantation loss, reduced numbers of live fetuses per litter, and reduced fetal body weights per litter. The incidence of fetal malformations and variations was increased. Oral administration of VPA produced maternal toxicity, developmental toxicity, and teratogenicity. The Fischer 344 rat is thus susceptible to known rodent teratogens by both the dermal and oral routes. It is concluded that 2-EH is not developmentally toxic by the dermal route in the Fischer 344 rat at and below treatment levels which produce maternal toxicity. PMID- 1516775 TI - Subchronic toxicity, metabolism, and pharmacokinetics of the aminobenzamide anticonvulsant ameltolide (LY201116) in rhesus monkeys. AB - Studies were undertaken to define the subchronic toxicologic profile of ameltolide, an aminobenzamide anticonvulsant, in young adult rhesus monkeys. Daily doses of ameltolide, dissolved in 10% aqueous acacia, were administered orally via nasogastric intubation at dosages of 5, 10, 20, 45, and 100 mg/kg. Deaths occurred in two monkeys, one each at 45 and 100 mg/kg, which were directly attributable to the effects of the compound. The exact cause of death in these monkeys was not readily apparent. A third monkey (100 mg/kg) was killed moribund on Day 82 of the study due to conditions not directly related to treatment. Clinical signs in monkeys treated with 100 mg/kg included convulsions, diarrhea, weakness, inappetance, vomition, and ataxia. Plasma concentrations of the N acetyl metabolite of ameltolide were greater than parent drug concentrations by one to two orders of magnitude. Mean area under the plasma-time curve (AUC) values for ameltolide were larger than expected at doses of 20 mg/kg or greater, while AUC values for the metabolite were less than expected at 45 and 100 mg/kg. These findings suggest a saturation of metabolism and/or excretion at the two higher doses. Similar nonlinearity was seen with mean peak concentrations for both parent and metabolite. No specific target organ toxicity was found on histological evaluation of tissue sections. Methemoglobin concentration was increased in monkeys given 45 or 100 mg ameltolide/kg. This change was not considered to be toxicologically important as there were no corroborative clinical, gross, or histopathological findings. Ameltolide administered by nasogastric intubation at doses up to 20 mg/kg/day for 3 months did not cause any toxicologically important alterations in rhesus monkeys. PMID- 1516776 TI - Joint actions of developmental toxicants in Xenopus embryos: binary mixtures of DNA synthesis inhibitors. AB - The joint toxic action for each of three binary combinations of DNA synthesis inhibitors was examined at concentrations that induce malformations in Xenopus laevis embryos. The three compounds, hydroxyurea, cytosine arabinoside, and 5 fluorouracil, which each inhibit a different enzyme involved in DNA synthesis, were selected for joint action testing to help determine whether joint action types are related to general modes of action (e.g., inhibit DNA synthesis) or to specific biochemical/molecular mechanisms. Three mixtures were tested, in 96-hr static-renewal tests, for each combination. Each combination was tested on three separate occasions. Using toxic unit analysis, the joint action for induction of malformations was generally antagonism, although response addition was observed for certain mixtures. An antagonistic joint action represents the phenomenon of interaction. Therefore, the tests were ineffective in determining whether a concentration addition joint action depicts two compounds that induce malformations by the same general mode of action or by the same specific mechanism of action. PMID- 1516777 TI - An examination of the association between maximum-tolerated dose and carcinogenicity in 326 long-term studies in rats and mice. AB - The association between rodent carcinogenicity and maximum-tolerated dose (MTD) was evaluated in 326 long-term carcinogenicity studies in mice and rats. Others investigating this association have focused primarily on positive studies, but our investigation considered all experimental outcomes. We found that chemicals with low MTDs were somewhat more likely to be rodent carcinogens than chemicals with high MTDs, but this association was limited primarily to gavage studies. Overall, the MTD was not a reliable predictor of whether or not a chemical would be a rodent carcinogen. Our investigation confirms that comparisons of carcinogenic potencies based only on positive studies may result in artifactually elevated estimates of the underlying association between chemical toxicity and rodent carcinogenicity and thus may also inflate the estimated interspecies correlation in carcinogenic response. Nevertheless, the results of our study are consistent with the frequently cited 75% concordance in carcinogenicity outcome between rats and mice. This concordance is quite high, particularly since 80% is approximately the maximum level of observable interspecies concordance achievable for a set of chemicals with relatively low carcinogenic potency, because of the variability in observed tumor responses that can induce false negative or false positive outcomes in either of the two species. Thus, the underlying qualitative interspecies correlation in carcinogenic response between rats and mice may be greater than is commonly recognized. PMID- 1516778 TI - A study of developmental toxicity of hydroquinone in the rabbit. AB - To obtain information on potential developmental toxicity, hydroquinone (HQ) was administered to pregnant New Zealand White rabbits (18 mated per dose group) in aqueous solution (0, 25, 75, or 150 mg HQ/kg/day) by gavage on Gestation Days (GD) 6 to 18. Caesarean sections were performed on GD 30. Doses of 75 and 150 mg/kg/day adversely affected feed consumption and/or body weights of dams during the treatment period. At these doses, however, treatment-related effects were not evident from physical observations, liver and kidney weights, premature delivery incidence, and caesarean sectioning data. The NOEL for maternal toxicity was 25 mg/kg/day. In the 150 mg/kg/day dose group, total incidences of external, visceral, and skeletal findings for fetuses did not differ statistically from controls. Slight, statistically insignificant, increases were found, however, in the incidences of ocular and minor skeletal malformations (micro-ophthalmia, vertebral/rib defects, angulated hyoid arch) on both a per fetus and a per litter basis. Under the conditions of this study, HQ at 150 mg/kg/day produced minimal developmental alterations in the presence of maternal toxicity. The NOEL for developmental toxicity was 75 mg/kg/day. PMID- 1516779 TI - Maternal and fetal tissue distribution of L-carnitine in pregnant mice: low accumulation in the brain. AB - The distribution of L-carnitine was studied by whole-body autoradiography in pregnant CD-1 mice at 1, 2, 3, and 6 hr after receiving L-[14C]carnitine. Highest concentrations of carnitine were found in maternal tissues including liver, placenta, kidney, myocardium, and choroid plexus. High retention of tissue carnitine in excess of blood levels suggests the existence of concentrative uptake mechanism. Labeled carnitine was not detectable in either maternal or fetal brain. This suggests that the brain barrier systems limit the access of L carnitine to the brain. In fetus, the level of carnitine was less than that seen in the maternal tissues, however, the tissue distribution was similar. The fetal tissue carnitine concentration increased with time. These findings suggest that relief of encephalopathy due to toxic organic anions in metabolic disorders following L-carnitine supplementation appears to be peripheral metabolic effects rather than direct access to the central nervous system. However, the physiological role for the concentrative uptake of L-carnitine by the choroid plexus remains to be determined. Transport of carnitine into fetal tissues via placenta further suggests the possibility of prenatal therapy in pregnancies at risk for certain inherited metabolic disorders. PMID- 1516780 TI - Reproductive study of acrolein on two generations of rats. AB - Four groups of 30 male and 30 female rats were intubated with 70 daily doses of acrolein at levels of 0, 1, 3, or 6 mg/kg in a dosing volume of 5 ml/kg. Rats within each dosing group (F0 generation) were then assigned to a 21-day period of cohabitation and dosing for females continued through cohabitation gestation and lactation. Males were euthanized after cohabitation. F1 generation rats were chosen from pups, and a similar pretreatment, cohabitation, gestation, and lactation regimen was accomplished resulting in F2 generation pups. Reproductive parameters, body weights, food consumption, and clinical signs were recorded and necropsies were carried out on all treated animals. Histopathologic exams were accomplished on selected reproductive tissues. In addition, gross lesions, target tissues, stomachs, and lungs were examined. For the most part, reproductive parameters were unaffected by acrolein treatment with the exception of reduced pup weights in the F1 generation pups at the high-dose level (6 mg/kg/day). Gastric lesions were noted consistently in high-dose animals and some mid-dose (3 mg/kg/day) rats. Erosions of glandular mucosa and hyperplasia/hyperkeratosis of the forestomach were the most frequent stomach lesions observed. Effects on body weight gains were noted frequently for the high-dose animals and achieved statistical significance in the mid-dose animals on several occasions. Mortality in all high-dose animals was elevated relative to control animals. Acrolein, therefore, cannot be considered a selective reproductive toxin in the rat, but does produce toxicological effects down to a dosing level of 3 mg/kg/day. PMID- 1516781 TI - The developmental toxicity of diethylene and triethylene glycol dimethyl ethers in rabbits. AB - Diethylene glycol dimethyl ether (diEGdiME) and triethylene glycol dimethyl ether (triEGdiME), widely used organic solvents, are structurally related to several compounds that produce reproductive and developmental toxicity, including teratogenicity in laboratory animals. In the present studies, diEGdiME (0, 25, 50, 100, or 175 mg/kg/day) or triEGdiME (0, 75, 125, 175, or 250 mg/kg/day) were administered by gavage in distilled water to timed-pregnant New Zealand white rabbits (15-25 dams/group) during major organogenesis [Gestational Days (gd) 6 19]. Treated females were euthanized on gd 30, uterine contents were examined, and live fetuses were examined for morphological alterations. In the diEGdiMe study, evidence of maternal toxicity, per se, was observed only at 175 mg/kg/day with 15% mortality among treated females compared to 4% among controls. No significant maternal toxicity was observed in the 25 mg/kg/day group, and only minimal maternal toxicity (decreased maternal weight gain during treatment) was observed at 50 and 100 mg/kg/day compared to the vehicle control group. The no observed-adverse-effect level for developmental toxicity in rabbits for diEGdiME was 50 mg/kg/day. The incidences of prenatal mortality and malformed live fetuses were significantly above controls at 100 and 175 mg/kg/day. Malformations observed most frequently included fusion of ribs to each other and hydronephrosis; clubbing of the limbs without underlying bone deformities, a variation, was also observed. In the triEGdiME study, clinical signs of toxicity were minimal and there was no increased maternal mortality. Maternal body weight and gravid uterine weight were significantly reduced at 250 mg/kg/day, whereas maternal weight gain during treatment was significantly depressed at doses of 175 mg/kg/day and above.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1516782 TI - Systemic toxicity of the heavy fraction of a coal coprocessing product in male rats following subchronic dermal exposure. AB - The systemic toxicity of a coal coprocessing product [heavy gas oil II (HGOII)] following subchronic, dermal exposure in male Sprague-Dawley rats was investigated. HGOII was applied to the dorsal skin daily at doses of 8.7, 20.8, 50.0, or 120.0 mg/kg body weight (bw) for 13 weeks. Another group of rats treated with a medium boiling coal liquefaction product (CLP) served as positive controls. Growth suppression and decreased food consumption were noted in the groups exposed to HGOII at 20.8 mg/kg and higher, and to CLP starting at the third week of treatment. Relative liver, kidney, and brain weights in the 20.8 mg/kg HGOII group and up were higher than those of the control. Increased spleen weight was observed in all HGOII-treated groups. CLP treatment also caused increased relative kidney and brain weights. Serum cholesterol was elevated in the HGOII-treated groups starting at 8.7 mg/kg while increased uric acid and lactate dehydrogenase were observed at 20.8 mg/kg and up. Decreased erythrocyte, hemoglobin, and platelet counts were observed at 20.8 mg/kg and higher. All HGOII treated groups had elevated reticulocytes. These biochemical and hematological changes were not observed in the CLP-treated group. Mild to marked histological changes were observed in the thyroid, thymus, liver, spleen, and bone marrow of HGOII groups. In contrast, morphological changes were relatively mild in CLP treated animals. Data from the present study demonstrated that the hematological endpoints were sensitive to the liquid fuels and that HGOII was more toxic than CLP.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1516783 TI - Age-related percutaneous penetration of 2-sec-butyl-4,6-dinitrophenol (dinoseb) in rats. AB - [14C]Dinoseb was applied to previously clipped back skin of 33- and 82-day-old female Fischer 344 rats at a dosage range of 210-2680 nmol/cm2. Radioactivity in the treated skin, tissues, urine, and feces was determined at 1, 6, 24, 48, 72, and 120 hr following dermal application. In vitro dermal absorption of [14C]dinoseb was also measured in rats of the same age by static and flow-through methods. In vivo dermal absorption in both young and adults appeared biphasic with 55.6 and 82.7% of the recovered dose, respectively, penetrating in 72 hr. In vitro measurements of skin absorption at 72 hr with static cells showed higher values in young and lower values in the adult compared to in vivo dermal absorption values. In vitro flow-through measurements at 72 hr gave lower dermal absorption values for both young and adult rats, compared to in vivo values. Following in vivo application, adults excreted about 70% of the total recovered dose in urine, 16% in feces, and retained 7% in the body at 120 hr. HPLC analysis of urine collected at 24 hr from adults administered [14C]dinoseb showed extensive metabolism of parent. Excretion and retention results for young were about 80% of the adult values, which also was the young to adult ratio of dermal penetration. Blood had the highest concentration of dinoseb-derived radioactivity of the tissues examined. The kidney to blood ratio averaged 0.60 in young and 0.41 in adults, while the liver and carcass to blood ratio averaged 0.18 in young and 0.11 in adult. Dermal absorption in young rats was slightly less than that in adults, and the subsequent kinetics of retention and excretion appeared different. In vitro dermal penetration of dinoseb was usually lower than in vivo absorption. PMID- 1516784 TI - Toxicology of maternally ingested trichloroethylene (TCE) on embryonal and fetal development in mice and of TCE metabolites on in vitro fertilization. AB - Trichloroethylene (TCE), an industrial solvent, is a soil and ground water contaminant found across the United States. The metabolism and carcinogenic potential of TCE have been studied extensively in the past 15 years yet there is little information on the chemical's possible effects on reproduction. No reference to the reproductive effects in mice of TCE by oral administration exists in the literature. In this study, female B6D2F1 mice were gavaged from Days 1 to 5, 6 to 10, or 11 to 15 (Day 1 = vaginal plug) with TCE in corn oil at 0, 1/10, and 1/100 of the oral LD50. Weights of mice were recorded and the livers and kidneys were weighed and preserved in 10% buffered formalin. Litters were counted, sexed, weighed, and measured for crown-rump length until weaning on Day 21 and some animals were allowed to develop to 6 weeks of age. At this time, a minimum of two litters from each dose were killed and gonads removed, weighed, and preserved in Bouin's fixative. Litters were also assessed for developmental abnormalities. No maternal or reproductive effect of TCE was seen at either dose level. TCE, administered consecutively on Days 1 to 5, 6 to 10, and 11 to 15 of pregnancy, does not appear to be a potential reproductive toxicant up to 1/10 the oral LD50. In a second series of studies, TCE and its metabolites dichloroacetic acid (DCA), trichloroacetic acid (TCAA), and trichloroethanol (TCOH) were added to culture media to assess the toxic effects on in vitro fertilization (IVF) in mice.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1516785 TI - Accumulation of Cd(II) in the CNS depending on the route of administration: intraperitoneal, intratracheal, or intranasal. AB - The uptake and subsequent neuronal transport of certain heavy metals in the olfactory mucosa may be a major means by which these compounds gain access to the CNS. To contrast olfactory versus blood-borne routes of exposure, three groups (n = 4) of adult Long-Evans rats were exposed to solutions of radiolabeled CdCl2. Exposure was by one of three routes: unilateral intranasal instillation (IN), intratracheal lavage (IT), or intraperitoneal injection (ip). The dose level for the intranasal route was 30 microliters of 1 microM CdCl2 labeled with 1 microCi 109Cd. For IT and ip, the dose was 30 microliters of 1 microM CdCl2 diluted to 300 microliters in saline and labeled with 1 microCi 109Cd. Rats were euthanized 24 hr after exposure, tissue samples were taken, and radioactivity was counted. Cd levels were low in the olfactory bulbs of rats exposed either intratracheally or intraperitoneally. However, in rats intranasally exposed, Cd levels were nearly 40 x higher in olfactory bulbs ipsilateral to the exposed side than in those on the contralateral side. With all routes of exposure, Cd levels in brain samples were only slightly elevated. These results suggest that for certain airborne toxicants, especially those that are excluded from the CNS by the blood brain barrier, the olfactory system may provide a direct route of entry into the CNS. PMID- 1516786 TI - Pulmonary bioavailability and fine particle enrichment of 2,3,7,8 tetrachlorodibenzo-p-dioxin in respirable soil particles. AB - The pulmonary bioavailability of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) and the enrichment of polychlorinated dioxins (PCDDs) and furans (PCDFs) in fine particles were evaluated to assess the implications that these factors have on risk and exposure assessments. Respirable subfractions of PCDD-contaminated soil from a former 2,4,5-trichlorophenoxyacetic acid manufacturing site were isolated by chemical dispersion and gravity sedimentation. Analysis of the subfractions revealed that there was a size-dependent enrichment of PCDDs and PCDFs, with smaller particles more highly contaminated. TCDD was enriched up to 33-fold as compared to unfractionated soil. Soil and laboratory-recontaminated gallium oxide, which served as the positive control, were administered by intratracheal instillation to female Sprague-Dawley rats. Animals were terminated up to 28 days following treatment and pulmonary bioavailability of TCDD was assessed by hepatic enzyme induction and TCDD concentration. Enzyme induction was dependent on the duration of exposure with up to 56 and 918% increases in cytochrome P450 and aryl hydrocarbon hydroxylase (AHH) activity, respectively, following exposure to PCDD contaminated soil. There was no significant difference in AHH induction between animals which received contaminated soil and those treated with the positive control. Hepatic concentration of TCDD in soil-exposed rats was 115, 101, and 179% of positive controls at 1, 7, and 28 days post-treatment, suggesting that the soil or cocontaminants influenced retention of TCDD in the liver. These data indicate that the relative pulmonary bioavailability of TCDD on respirable soil particles is 100% as compared to laboratory-recontaminated gallium oxide and that PCDDs and PCDFs are highly enriched on respirable particles.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1516787 TI - Developmental toxicity of 2,4,5-trichlorophenoxyacetic acid (2,4,5-T). I. Multireplicated dose-response studies in four inbred strains and one outbred stock of mice. AB - A large-scaled multireplicated developmental toxicity study was conducted in various strains/stocks of mice with the herbicide, 2,4,5-trichlorophenoxyacetic acid (2,4,5-T), by gavage on Gestational Days 6 through 14. The most important attributes of the study design were replicated test groups, a minimum of four dose levels per replicate, use of multiple stocks/strains of animals to obtain an estimate of the range in sensitivities due to genotype, complete pathological evaluation of maternal animals, and histopathological as well as teratological evaluation of the fetuses. Developmental toxicity was observed at doses below those producing discernible or measurable maternal toxicity. Regression and/or probit analyses were conducted to determine whether a dose-response relationship existed. Reduced fetal weight and increased incidence of cleft palate and embryolethality were the most significant prenatal effects of 2,4,5-T exposure observed in this study. Each strain/stock exhibited a dose-related decrease in fetal weight with the CD-1 mice having the steepest slope and the A/J mice having the shallowest slope. There was a striking similarity among the slopes of the dose-response curves for the various strains/stocks. The mean incidence of embryolethality in the A/J strain was significantly greater than that of the other strains or stocks. There was substantial variation among replicates within strains. The use of the replicated study design was logistically necessary due to the magnitude of the study and it also served to increase the statistical power of the study. PMID- 1516788 TI - Developmental toxicity of 2,4,5-trichlorophenoxyacetic acid (2,4,5-T). II. Multireplicated dose-response studies with technical and analytical grades of 2,4,5-T in four-way outcross mice. AB - A series of multireplicated developmental toxicity studies were conducted in four way outcross mice and CD-1 outbred mice administered either analytical or technical grades of 2,4,5-trichlorophenoxyacetic acid (2,4,5-T) by gavage on Gestational Days 6 through 14. The formulations of 2,4,5-T differed by a factor of 10-fold in 2,3,7,8-tetrachlorodibenzo-p-dioxin levels. Reduced fetal weight and increased incidences of cleft palate and embryolethality were the most significant prenatal effects of both formulations of 2,4,5-T observed in all strains/stocks of mice. Both the outcross and outbred mice exhibited a dose response relationship with each of the above endpoints and the dose-response curves were parallel. There were no embryotoxic or fetotoxic differences between the technical and analytical grades of 2,4,5-T with regard to extent of fetal weight reduction, resorption rate, or cleft palate incidence. There was little difference in the results between the four-way outcross mouse and the CD-1 outbred mouse. PMID- 1516789 TI - One-year dietary toxicity study with methidathion in beagle dogs. AB - The purpose of this study was to determine the chronic toxicity of methidathion, an organophosphate insecticide, in dogs. Groups of beagle dogs, four/sex/dose, were fed methidathion at constant dietary concentrations of 0, 0.5, 2, 4, 40, or 140 ppm for 1 year. The equivalent daily dosages were approximately 0, 0.02, 0.07, 0.15, 1.4, and 4.7 mg/kg. There were no deaths or adverse clinical signs associated with the treatment. Weekly body weights and weight gains were not affected. Mean daily food consumption was reduced in male dogs given the 140-ppm diet. Major treatment-related effects were cholestasis, chronic inflammation in the liver, and cholinesterase (ChE) inhibition. The liver effects were indicated by gross and microscopic pathologic findings as well as moderate increases in serum bile acids and enzyme activities (alanine aminotransferase, aspartate aminotransferase, sorbitol dehydrogenase, and alkaline phosphatase) in all dogs receiving greater than or equal to 40 ppm. RBC ChE was inhibited in males at greater than or equal to 40 ppm and in females and 140 ppm. Brain ChE was inhibited in both sexes at 140 ppm; the magnitude of inhibition relative to control was slightly greater with the cerebellar fraction than with the cerebral fraction. Serum ChE was not affected at any dose level. In conclusion, liver was the target organ in beagle dogs given greater than or equal to 40 ppm (equivalent to 1.4 mg/kg/day) methidathion in diet for 1 year. The no-observable-effect level was 4 ppm (0.15 mg/kg/day) for both liver cholestasis and ChE inhibition. PMID- 1516790 TI - Evaluating the effects of acrylamide and 3,3'-iminopropionitrile (IDPN), using behavioral (functional observational battery and motor activity) and neuropathological end points. PMID- 1516791 TI - [Ultrastructural changes in lysosomal apparatus of human platelets in pathologic states]. AB - The author has presented the results of electron-microscopic and electron histochemical investigations of the lysosomal apparatus in human platelets under the action of certain agents (acetylsalicylic acid, vincristine) and in pathologic states (acute leukemia, myeloproliferative diseases, autoimmune thrombocytopenic purpura). Interrelation has been recorded between ultrastructural changes in the lysosomal apparatus and parameters of platelet functional activity. Biogenesis of lysosomal enzymes has been considered basing on molecular biology of the cell. PMID- 1516792 TI - [Dynamics of blood lymphocyte blast-transformation parameters during hemosorption in patients with gastric ulcer]. AB - The influence of autotransfusions of hemosorbent-treated blood on parameters of DNA-synthetic activity of blood lymphocytes was studied in 114 patients with gastric ulcer. A statistically significant increase in parameters of DNA synthetic activity of lymphocytes was recorded simultaneously with the appearance of morphological signs of blast transformation on electrograms. A conclusion has been made on association of lymphocyte blastogenesis under the influence of autotransfusions with the process of ulcerous sanagenesis acceleration. PMID- 1516793 TI - [Hemostasis disorders in the familial form of Louis-Bar syndrome with symptoms of hemorrhagic diathesis]. PMID- 1516794 TI - [Rheologic and hemocoagulation parameters in patients with multiple myeloma during therapy]. PMID- 1516795 TI - [Changes in the organ of vision in beta-thalassemia: clinical and morphologic parallels]. AB - Ophthalmologic examination and morphologic investigations of the spleen were conducted in 10 patients with beta-thalassemia. Pathologic changes of vascular and dystrophic character were detected in the organ of vision, symptoms of angiopathy, hemosiderosis and spleno-cirrhosis were recorded in the spleen tissue. Clinical changes in the organ of vision were correlated with morphological shifts in the spleen tissue. A conclusion has been made that ophthalmologic examination of thalassemia patients could be useful for evaluation of severity of the main disease and effectiveness of the treatment conducted. PMID- 1516796 TI - [Changes in the parameters of functional systems of donors undergoing apparatus plasmacytapheresis]. AB - Apparatus plasmacytapheresis resulted in the lowering of total protein level and serum iron content in the blood as compared to the initial values. At the same time these parameters were within the range of reference standards and reached the initial levels 3-4 weeks after the completion of the plasmacytapheresis cycle. PMID- 1516797 TI - [Iron metabolism, hemopoiesis, prevention and treatment of iron deficiency anemia in multiparous women]. AB - A total of 160 multiparous women with iron deficiency anemia (IDA) who have 4 and more children were under study. Hemoglobin parameters in patients with non-severe anemia (n = 64) fluctuated from 119 to 90 g/l, in patients with moderate severity (n = 60) from 89 to 70 g/l, in those with severe stage of anemia--69 g/l and lower. The latent anemia group consisted of women whose hemoglobin values were 120 g/l and higher, however, the figures characterizing serum iron, transferrin and ferritin content evidenced iron deficiency. Parameters of serum iron, transferrin and ferritin metabolism were studied in all the patients. Decreased levels of serum iron and ferritin and a compensatory increase of transferrin content were recorded. Manifest signs of acquired dyserythropoiesis and a significant increase of ineffective erythropoiesis (34.96 +/- 0.89%) were demonstrated in myelograms. It has been recommended that routine measures used for the treatment of IDA in multiparous women should be supplemented by anabolic agents and blood substitutes for protein parenteral nutrition. PMID- 1516798 TI - [Analysis of sources of error in determining the ABO blood group system using monoclonal anti-A and anti-B antibodies]. PMID- 1516799 TI - A test-system for evaluation of activity and specificity of isoagglutinating sera. PMID- 1516800 TI - [Current tactics in reducing hazards of virus infection transmission during blood transfusion]. PMID- 1516801 TI - [Mechanism of action of pafencil on sensitive and resistant tumor cells]. PMID- 1516802 TI - [Morphometric parameters of malignant cells in non-leukemic hemoblastosis with primary lymph node involvement]. AB - Morphometric studies were conducted to distinguish reactive and malignant lymphoid processes and to obtain a more objective and reproducible grading system for non-Hodgkin's lymphomas (NHL). Twenty-three untreated patients (3 with reactive lymphadenitis, 2 with diffuse lymphomas, 18 with lymphosarcomas) were studied. The sections of lymph nodes were stained with 50% aqueous silver nitrate solution and then counter-stained with methylene blue. MOP-Videoplan (Reichert, Austria) image analyzer was used for morphometry. The size and shape of nucleus, number and position of nucleoli and the number of silver grains (K1) and relative size (K2) of each grain were investigated. The computer classification of lymphoid cells based on a stepwise linear discriminant analysis resulted in 63% correctly classified cells. Among seven most discriminating parameters, the nucleoli area and the number and size of silver grains demonstrated the highest correlation with malignancy. The data obtained have evidenced that nucleolar parameters can be applied to computer classification of lymphoid neoplastic cells and for objective grading of NHL. PMID- 1516803 TI - Cloning of a Bacteroides fragilis chromosomal determinant coding for 5 nitroimidazole resistance. AB - Strain BF8 is a plasmid-free Bacteroides fragilis, resistant to 5-nitroimidazole (5-Ni) antibiotics (metronidazole, ornidazole and tinidazole). The resistance was transferable by conjugation into Bacteroides fragilis BF638R. The total DNA of a Nir transconjugant was used for the construction of a Sau3A genomic library in a B. fragilis cloning vector pFK707 delta H1 (4.2 kb). By electrotransformation of strain BF638R, a recombinant plasmid containing an insert of 5.4 kb was obtained which conferred to the host strain the resistance to 5-Ni. The physical map of the insert was established. After deletion analysis of the insert, the Nir determinant was localized on a HpaII-HincII fragment of 1.6 kb in size. This Nir determinant has been compared by Southern-blot analysis with other Bacteroides Nir determinants of plasmid origin. PMID- 1516804 TI - OmpF channel permeability of quinolones and their comparison with beta-lactams. AB - The diffusion rates of nalidixic acid, ofloxacin and ofloxacin's two optically active isomers through OmpF channels were measured in proteoliposomes and compared with the rates of beta-lactams. The four quinolones showed high diffusion rates, exceeding that of cephaloridine and being comparable to imipenem. There was no significant difference in diffusion rate between nalidixic acid and ofloxacin, or between the two optically active isomers. The diffusion rates of enoxacin and norfloxacin were also estimated to be higher than many beta lactams. PMID- 1516805 TI - Effect of restrictive conditions on the growth and morphology of a temperature sensitive mannose-requiring mutant of Aspergillus nidulans. AB - When incubated at 45 degrees C in the absence of added mannose, pregrown hyphae of a temperature-sensitive, mannose-relief mutant (mnrA455) of Aspergillus nidulans grew normally for a short time (4-5 h) before exhibiting an abnormal morphology consisting of the production by hyphae of discrete spherical swellings called balloons. These swellings could be up to 10 microns in diameter and were produced either at or behind the hyphal apex. Often only one swelling was produced in association with each hyphal tip, but in a significant minority of cases (approximately 19.6%) a second balloon was produced in close association with the first. Hyphal tip extension slowed before and during balloon formation, but growth at individual tips did not usually stop when a balloon began to be formed in the same hypha. All tip extension ceased after approximately 8 h in cultures maintained at 45 degrees C. However, normal growth resumed 45-60 min after transfer of such a culture to the permissive temperature of 37 degrees C even after 48 h at 45 degrees C. Electron microscopic examination indicated that balloons consistently had thicker walls than the surrounding hyphae but that no accumulation of cytoplasmic vesicles was apparent within them. This indicates that a modification of wall structure, probably including deposition of new wall material, was caused by a mannose deficiency, but that this altered wall synthesis and attendant hyphal swelling was not due to diversion of the normal vesicle-mediated tip-extension system to the side walls of hyphae. PMID- 1516806 TI - Mycobacterium avium and Mycobacterium intracellulare chromatotypes defined by curvilinear gradient HPLC of mycolic acids. AB - Seventy-nine strains of Mycobacterium avium complex bacteria (MAC), previously characterized by genetic probe analysis, were assayed using two methods of reverse phase high-performance liquid chromatography (HPLC) that employed curvilinear gradients. Although different in column length and cycle time, the methods produced equivalent results, yielding seven distinct chromatographic patterns (chromatotypes) of M. avium and M. intracellulare based on the ratio of mycolate concentrations in the late vs. the middle of three peak clusters (L:M ratio). The M. avium strains (n = 36) were assigned to chromatotypes 1 through 4 (L:M ratios less than 3), and the M. intracellulare strains (n = 25) to chromatotypes 5 through 7 (L:M ratios greater than 4). Of 18 Mycobacterium 'X' strains, seven resembled M. avium, seven others resembled M. intracellulare, and four were intermediate between M. avium and M. intracellulare. PMID- 1516807 TI - Re-examination of the metabolic potentials of the acetogens Clostridium aceticum and Clostridium formicoaceticum: chemolithoautotrophic and aromatic-dependent growth. AB - Both Clostridium formicoaceticum and Clostridium aceticum grew chemolithoautotrophically on carbon monoxide plus CO2 in defined medium in the absence of carbohydrates, amino acids, or other carbon and energy sources. Formate supported the growth of both organisms as well in both defined and undefined media (both of which also contained CO2). Hydrogen was stimulatory to the growth of C. formicoaceticum upon first transfer into H2-enriched formate medium; however, neither chemolithoautotrophic growth at the expense of H2 plus CO2 nor hydrogenase could be demonstrated with this acetogen. Consistent with recent findings with other acetogens, numerous aromatic compounds were utilized by C. aceticum and C. formicoaceticum: (i) aromatic methoxyl groups were O demethylated; (ii) aromatic acrylates were reduced; and (iii) aromatic aldehydes were oxidized. These findings demonstrate that the metabolic potentials of these two acetogens are greater than previously recognized. PMID- 1516808 TI - Rapid identification of Aerococcus viridans using the polymerase chain reaction and an oligonucleotide probe. AB - A polymerase chain reaction/oligonucleotide probe method was developed for the specific identification of the Gram-positive bacterium Aerococcus viridans. Primers for the enzymatic amplification reaction were designed from specific sequences within the 16S rRNA. The method was also highly sensitive and 10 cfu of A. viridans could be detected in 5 h although the reliability of detection was poor in mixed cultures with Escherichia coli. PMID- 1516809 TI - The DNA polymerases of Leishmania mexicana. AB - Two previously isolated DNA polymerases from the parasitic protozoan Leishmania mexicana were further characterized by exposure to inhibitors of mammalian DNA polymerases. DNA polymerase A, a high molecular mass enzyme, and DNA polymerase B, a beta-like DNA polymerase were compared to each other and to their mammalian counterparts regarding pH optimum, utilization of templates, and response to various inhibitors and ionic strengths. The results suggest that the DNA polymerases from L. mexicana differ from the host enzymes and may offer a target for chemotherapeutic intervention. PMID- 1516810 TI - Constitutive transcription of the gene for metallothionein in a cadmium-resistant yeast. AB - A cadmium-resistant strain of Saccharomyces cerevisiae produces a cadmium metallothionein encoded by the CUP1 gene as does a copper-resistant strain. The mechanism of expression of the gene is inducible by copper ions in the copper resistant strain. However, assays of CUP1-specific mRNA revealed that the transcription of the CUP1 gene in the cadmium-resistant strain is constitutive and the rate of transcription is further increased by exposure to cadmium or copper ions. This result was confirmed by the appearance of constitutive expression segregants from diploid crosses between the cadmium-resistant strain and a strain with a reporter gene having the promoter of CUP1. PMID- 1516811 TI - Nitrosating activity in Escherichia coli. AB - Nitrosation activity was measured in Escherichia coli isolates and a range of nitrite reductase (nir) mutants. Activity was only detected in intact cells and could be inhibited by a number of treatments such as sonication and osmotic shock. Aerobically-grown cells had highest nitrosation activity compared to oxygen-limited ones. Inclusion of nitrite in growth media induced high activities of nitrite reductase and for some isolates, nitrosation. Analysis of nir mutants identified two which were unable to nitrosate. This result suggested that NADH dependent nitrite reductase was implicated either directly or indirectly in nitrosation. PMID- 1516812 TI - Dual effect of monovalent cations on the glucose-induced transient increase in the rate of DMP influx into Saccharomyces cerevisiae. AB - The transient increase in the rate of 2-(4-di-methyl-aminostyryl)-1 ethylpyridinium (DMP) influx in Saccharomyces cerevisiae caused by addition of glucose to a suspension of non-metabolizing cells at relatively high pH can be prevented by monovalent cations. Their concentrations for half-maximum inhibition of DMP uptake are of the same order of magnitude as the corresponding Km values for their uptake into yeast cells. It is argued that the inhibition of DMP uptake by monovalent cations is caused by a fast depolarization of the cell membrane and a second further decrease in the rate of DMP uptake. The latter effect develops slowly with time and depends upon the extent of accumulation of the monovalent cations in the cells. PMID- 1516813 TI - Sixty years ago: the 1932 International Congress of Genetics. PMID- 1516814 TI - Genetic recombination in bacteriophage T4: single-burst analysis of cosegregants and evidence in favor of a splice/patch coupling model. AB - To reveal the structure of penultimate DNA intermediates in T4 bacteriophage recombination, resolution of which produces free recombinant molecules, a single burst analysis of the recombinant progeny was made in multifactor crosses, enabling one to determine quantitatively the different recombinants generated by one or two exchanges within the same chromosome segment. It was found that double and single exchanges are highly correlated in T4 recombination. These results were interpreted as evidence for simultaneous formation of a splice/patch pair as the primary recombination products. A recombination model called here the "splice/patch coupling model" is presented according to which resolution of a single DNA intermediate results in two linear heterozygous molecules containing a patch and a splice, respectively, in homologous positions. PMID- 1516815 TI - Mechanisms of directed mutation. AB - Spontaneous mutants arise among nondividing populations of Escherichia coli in apparent response to selective conditions. In this report we investigate several hypotheses to account for the role of selection in the production of these "directed" or "adaptive" mutations. We found that the Lac+ phenotypes of some mutants that arise late after lactose selection are due to suppressor mutations that are unlinked to the mutant lacZ allele; thus the production of these Lac+ mutants does not require an information flow from successful proteins back to the DNA that encodes them. Transcriptional induction of the lac operon, even in the presence of another, utilizable carbon source, did not stimulate the occurrence of Lac+ mutants in the absence of lactose, indicating that the role of the selective agent is not merely to induce transcription. The absence of two DNA repair pathways-methyl-directed mismatch repair and alkylation repair-also did not result in an accumulation of Lac+ mutants in the absence of lactose, suggesting that these repair pathways are not normally responsible for correcting transient variants that might arise in the absence of selection. However, in one case the Lac+ mutation is likely to be due to a miscoding lesion occurring on the nontranscribed DNA strand, indicating that, at least in this instance, DNA replication is required before directed mutations can arise. PMID- 1516816 TI - Expression of the maize MnSod (Sod3) gene in MnSOD-deficient yeast rescues the mutant yeast under oxidative stress. AB - Superoxide dismutases (SOD) are ubiquitous in aerobic organisms and are believed to play a significant role in protecting cells against the toxic, often lethal, effect of oxygen free radicals. However, direct evidence that SOD does in fact participate in such a protective role is scant. The MnSOD-deficient yeast strain (Sod2d) offered an opportunity to test the functional role of one of several SOD isozymes from the higher plant maize in hopes of establishing a functional bioassay for other SODs. Herein, we present evidence that MnSOD functions to protect cells from oxidative stress and that this function is conserved between species. The maize Sod3 gene was introduced into the yeast strain Sod2d where it was properly expressed and its product processed into the yeast mitochondrial matrix and assembled into the functional homotetramer. Most significantly, expression of the maize Sod3 transgene in yeast rendered the transformed yeast cells resistant to paraquat-induced oxidative stress by complementing the MnSOD deficiency. Furthermore, analyses with various deletion mutants of the maize SOD 3 transit peptide in the MnSOD-deficient yeast strain indicate that the initial portion (about 8 amino acids) of the maize transit peptide is required to direct the protein into the yeast mitochondrial matrix in vivo to function properly. These findings indicate that the functional role of maize MnSOD is conserved and dependent on its proper subcellular location in the mitochondria of a heterologous system. PMID- 1516818 TI - Characterization of Caenorhabditis elegans lectin-binding mutants. AB - We have identified 45 mutants of Caenorhabditis elegans that show ectopic surface binding of the lectins wheat germ agglutinin (WGA) and soybean agglutinin (SBA). These mutations are all recessive and define six genes: srf-2, srf-3, srf-4, srf 5, srf-8 and srf-9. Mutations in these genes fall into two phenotypic classes: srf-2, -3, -5 mutants are grossly wild-type, except for their lectin-binding phenotype; srf-4, -8, -9 mutants have a suite of defects, including uncoordinated movement, abnormal egg laying, and defective copulatory bursae morphogenesis. Characterization of these pleiotropic mutants at the cellular level reveals defects in the migration of the gonadal distal tip cell and in axon morphology. Unexpectedly, the pleiotropic mutations also interact with mutations in the lin 12 gene, which encodes a putative cell surface receptor involved in the control of cell fate. We propose that the underlying defect in the pleiotropic mutations may be in the general processing or secretion of extracellular proteins. PMID- 1516817 TI - Isolation of crt mutants constitutive for transcription of the DNA damage inducible gene RNR3 in Saccharomyces cerevisiae. AB - Ribonucleotide reductase is an essential enzyme that catalyzes the rate limiting step for production of the deoxyribonucleotides required for DNA synthesis. It is encoded by three genes, RNR1, RNR2 and RNR3, each of which is inducible by agents that damage DNA or block DNA replication. To probe the signaling pathway mediating this DNA damage response, we have designed a general selection system for isolating spontaneous trans-acting mutations that alter RNR3 expression using a chromosomal RNR3-URA3 transcriptional fusion and an RNR3-lacZ reporter plasmid. Using this system, we have isolated 202 independent trans-acting crt (constitutive RNR3 transcription) mutants that express high levels of RNR3 in the absence of DNA damaging agents. Of these, 200 are recessive and fall into 9 complementation groups. In some crt groups, the expression of RNR1 and RNR2 are also elevated, suggesting that all three RNR genes share a common regulatory pathway. Mutations in most CRT genes confer additional phenotypes, among these are clumpiness, hydroxyurea sensitivity, temperature sensitivity and slow growth. Five of the CRT genes have been identified as previously cloned genes; CRT4 is TUP1, CRT5 is POL1/CDC17, CRT6 is RNR2, CRT7 is RNR1, and CRT8 is SSN6. crt6-68 and crt7-240 are the first ts alleles of RNR2 and RNR1, respectively, and arrest with a large budded, cdc terminal phenotype at the nonpermissive temperature. The isolation of crt5-262, an additional cdc allele of POL1/CDC17, suggests for the first time that directly blocking DNA replication can provide a signal to induce the DNA damage response. crt2 mutants show a defect in basal level expression of RNR1-lacZ reporter constructs. These are the first mutants isolated in yeast that alter the regulation of DNA damage inducible genes and the identification of their functions sheds light on the DNA damage sensory network. PMID- 1516819 TI - Mosaic analysis gives an estimate of the extent of genomic involvement in the development of the visual system in Drosophila melanogaster. AB - To investigate the role of vital loci in the development of the visual system of Drosophila, we induced mitotic recombination in individuals heterozygous for recessive organismal lethals and selected for analysis the resulting mosaics with homozygous mutant eye clones. Heads bearing clones were serially sectioned, silver-stained and examined for aberrations in the ommatidia and the neural structures to which they project. In our screen of 68 lines bearing diepoxybutane induced X-linked lethals, 26 yielded few or no homozygous mutant clones (putative cell-lethals). Of the rest, 20 lines produced individuals with morphologically abnormal eye clones showing various degrees of aberrations in the ommatidial architecture. In 14 of these 20, the laminar cartridges innervated by the mutant clones were also disorganized. Clones with normal structure were found in 18 of the lines, and three lines were resistant to the induction of mitotic recombination. In a single line, comparatively normal clones in the eye projected to a lamina with subtle but consistent abnormalities. To the extent that we have a representative sample, these results suggest that about two-thirds of all vital genes may be essential for the normal assembly and neural connectivity of the eye. This points to a high degree of pleiotropy in the manner in which information in the genome of the fly is used in development. PMID- 1516820 TI - Mutations in the second-largest subunit of Drosophila RNA polymerase II interact with Ubx. AB - Specific mutations in the gene encoding the largest subunit of RNA polymerase II (RpII215) cause a partial transformation of a structure of the third thoracic segment, the capitellum, into the analogous structure of the second thoracic segment, the wing. This mutant phenotype is also caused by genetically reducing the cellular concentration of the transcription factor Ultrabithorax (Ubx). To recover mutations in the 140,000-D second-largest subunit of RNA polymerase II (RpII140) and determine whether any can cause a mutant phenotype similar to Ubx we attempted to identify all recessive-lethal mutable loci in a 340-kilobase deletion including this and other loci. One of the 13 complementation groups in this region encodes RpII140. Three RpII140 alleles cause a transformation of capitellum to wing but unlike RpII215 alleles, only when the concentration of Ubx protein is reduced by mutations in Ubx. PMID- 1516822 TI - Evolution of multilocus genetic structure in an experimental barley population. AB - Data from 311 selfed families isolated from four generations (F8, F13, F23, F45) of an experimental barley population were analyzed to determine patterns of change in character expression for seven quantitative traits, and in single-locus allelic frequencies, and multilocus genetic structure, for 16 Mendelian loci that code for discretely recognizable variants. The analyses showed that large changes in single-locus allelic frequencies and major reorganizations in multilocus genetic structure occurred in each of the generation-to-generation transitions examined. Although associations among a few traits persisted over generations, dynamic dissociations and reassociations occurred among several traits in each generation-transition period. Overall, the restructuring that occurred was characterized by gradual decreases in the number of clusters of associated traits and increases in the number of traits within each cluster. The observed changes in single-locus frequencies and in multilocus genetic structure were attributed to interplay among various evolutionary factors among which natural selection acting in a temporally heterogeneous environment was the guiding force. PMID- 1516821 TI - Single amino acid exchanges in separate domains of the Drosophila serendipity delta zinc finger protein cause embryonic and sex biased lethality. AB - The Drosophila serendipity (sry) delta (delta) zinc finger protein is a sequence specific DNA binding protein, maternally inherited by the embryo and present in nuclei of transcriptionally active cells throughout fly development. We report here the isolation and characterization of four ethyl methanesulfate-induced zygotic lethal mutations of different strengths in the sry delta gene. For the stronger allele, all of the lethality occurs during late embryogenesis or the first larval instar. In the cases of the three weaker alleles, most of the lethality occurs during pupation; moreover, those adult escapers that emerge are sterile males lacking partially or completely in spermatozoa bundles. Genetic analysis of sry delta thus indicates that it is an essential gene, whose continued expression throughout the life cycle, notably during embryogenesis and pupal stage, is required for viability. Phenotypic analysis of sry delta hemizygote escaper males further suggests that sry delta may be involved in regulation of two different sets of genes: genes required for viability and genes involved in gonadal development. All four sry delta alleles are fully rescued by a wild-type copy of sry delta, but not by an additional copy of the sry beta gene, reinforcing the view that, although structurally related, these two genes exert distinct functions. Molecular characterization of the four sry delta mutations revealed that these mutations correspond to single amino acid replacements in the sry delta protein. Three of these replacements map to the same (third out of seven) zinc finger in the carboxy-terminal DNA binding domain; interestingly, none affects the zinc finger consensus residues. The fourth mutation is located in the NH2-proximal part of the protein, in a domain proposed to be involved in specific protein-protein interactions. PMID- 1516823 TI - Estimating polygenic models for multivariate data on large pedigrees. AB - We have developed algorithms for the likelihood estimation of additive genetic models for quantitative traits on large pedigrees. The approach uses the expectation L-maximization (EM) algorithm, but avoids intensive computation. In this paper, we focus on extensions of previous work to the case of multivariate data. We exemplify the approach by analyses of bivariate data on a four generation, 949-member pedigree of the snail Lymnaea elodes, and on a three generation pedigree of the guppy Poecilia reticulata containing about 400 individuals. PMID- 1516824 TI - On the theory of partially inbreeding finite populations. III. Fixation probabilities under partial selfing when heterozygotes are intermediate in viability. AB - In a previous paper by the senior author, an approximation to the probability of survival was given for a mutant, which is originally present in a single heterozygote, in a population that reproduces partly by selfing and partly by random mating. The population was assumed to be very large, but the result obtained is general with regard to the level of dominance in viability. In this paper two errors which were made in that earlier work are corrected. A general approximate expression is then derived for the probability that an allele A is fixed in a partially self fertilizing population of size N, if its initial frequency is p, selection is weak and heterozygotes with the allele are exactly intermediate in viability compared with genotypes AA and AA. A rigorous proof is given for a special case that is a generalization of the classical binomial sampling model. In this case, but not in general, the approximate fixation probability is independent of the probability of reproduction by selfing. Some implications are discussed. PMID- 1516825 TI - Pax-5 encodes the transcription factor BSAP and is expressed in B lymphocytes, the developing CNS, and adult testis. AB - BSAP has been identified previously as a transcription factor that is expressed at early, but not late, stages of B-cell differentiation. Biochemical purification and cDNA cloning has now revealed that BSAP belongs to the family of paired domain proteins. BSAP is encoded by the Pax-5 gene and has been highly conserved between human and mouse. An intact paired domain was shown to be both necessary and sufficient for DNA binding of BSAP. Binding studies with several BSAP recognition sequences demonstrated that the sequence specificity of BSAP differs from that of the distantly related paired domain protein Pax-1. During embryogenesis, the BSAP gene is transiently expressed in the mesencephalon and spinal cord with a spatial and temporal expression pattern that is distinct from that of other Pax genes in the developing central nervous system (CNS). Later, the expression of the BSAP gene shifts to the fetal liver where it correlates with the onset of B lymphopoiesis. BSAP expression persists in B lymphocytes and is also seen in the testis of the adult mouse. All of this evidence indicates that the transcription factor BSAP may not only play an important role in B-cell differentiation but also in neural development and spermatogenesis. PMID- 1516826 TI - Hlf, a novel hepatic bZIP protein, shows altered DNA-binding properties following fusion to E2A in t(17;19) acute lymphoblastic leukemia. AB - Oncogenic conversion of transcription factors by chromosomal translocations is implicated in leukemogenesis. We report that the t(17;19) in acute lymphoblastic leukemia produces a chimeric transcription factor consisting of the amino terminal portion of HLH proteins E12/E47 (products of the E2A gene) fused to the basic DNA-binding and leucine zipper dimerization motifs of a novel hepatic protein called hepatic leukemia factor (Hlf). Hlf, which is not normally transcribed in lymphoid cells, belongs to the recently described PAR subfamily of basic leucine zipper (bZIP) proteins, which also includes Dbp and Tef/Vbp. Wild type Hlf is able to bind DNA specifically as a homodimer or as a heterodimer with other PAR factors. Structural alterations of the E2a-Hlf fusion protein markedly impair its ability to bind DNA as a homodimer compared with wild-type Hlf. However, E2a-Hlf can bind DNA as a heterodimer with other PAR proteins, suggesting a novel mechanism for leukemogenic conversion of a bZIP transcription factor. PMID- 1516827 TI - Ras mediates translation initiation factor 4E-induced malignant transformation. AB - Translation initiation factor eIF-4E binds to the eukaryotic mRNA 5' cap structure (m7 GpppN, where N is any nucleotide). eIF-4E is a limiting factor in translation and plays a key role in regulation of translation. We have shown previously that overexpression of eIF-4E in rodent fibroblasts results in tumorigenic transformation. eIF-4E also exhibits mitogenic activity when microinjected into serum-starved NIH-3T3 cells. To understand the mechanisms by which eIF-4E exerts its mitogenic property, we examined the involvement of the Ras signaling pathway in this activity. Here, we report that Ras is activated in eIF-4E-overexpressing cells, as the proportion of GTP-bound Ras is increased. Overexpression of the negative effector of cellular Ras, GTPase activating protein, causes reversion of the transformed phenotype. Furthermore, we show that neutralizing antibodies to Ras, or a dominant-negative mutant of Ras, inhibit the mitogenic activity of eIF-4E. We conclude that eIF-4E exerts its mitogenic and oncogenic activities by the activation of Ras. PMID- 1516828 TI - Stable synapsis of homologous DNA molecules mediated by the Escherichia coli RecA protein involves local exchange of DNA strands. AB - Escherichia coli RecA protein promotes stable synapsis between a single-stranded DNA and a homologous duplex DNA, resulting in the formation of a complex of RecA with three DNA strands. To gain insight into the molecular interactions responsible for DNA synapsis, the base-pairing status within the synaptic complex was analyzed by using dimethylsulfate and potassium permanganate as probes. The results indicate that the original base pairs in the parental duplex are disrupted; one strand is displaced and the other strand appears to be involved in Watson-Crick base-pairing with the incoming single-stranded DNA. The state of base-pairing thus resembles that of the end products of strand exchange and not a canonical DNA triple helix involving non-Watson-Crick base-pairing. The results also indicate that this local strand exchange can occur without homology at the ends of the DNA substrates (i.e., when axial rotation of the product heteroduplex with respect to the axis of the parental duplex is obstructed). Taken together, these results suggest that exchange of DNA strands mediated by RecA occur at or before the stage of stable DNA synapsis by a process that does not require DNA rotation. PMID- 1516829 TI - Yeast SNF2/SWI2, SNF5, and SNF6 proteins function coordinately with the gene specific transcriptional activators GAL4 and Bicoid. AB - The SNF2 (SWI2), SNF5, and SNF6 genes are required for transcription of many diversely regulated genes in Saccharomyces cerevisiae. Previously, we showed that SNF2, SNF5, and SNF6 function interdependently in transcriptional activation, possibly forming a heteromeric complex. Here, we present evidence that SNF6 has a more direct role in stimulating transcription than SNF2 and SNF5. The global effects of mutations in SNF2, SNF5, and SNF6 suggested that these SNF proteins may function coordinately with many gene-specific activators. We show that LexA GAL4 and LexA-Bicoid fusion proteins are both dependent on SNF2, SNF5, and SNF6 for activation of target genes containing one or multiple lexA operators. The stringency of the requirement for the SNF proteins varies with the activator, the number of binding sites for the activator, and the target promoter. Thus, these SNF proteins appear to represent a class of intermediary proteins that facilitate transcriptional activation by gene-specific regulatory proteins. PMID- 1516830 TI - The acidic activator GAL4-AH can stimulate polymerase II transcription by promoting assembly of a closed complex requiring TFIID and TFIIA. AB - The assembly of activated RNA polymerase II (pol II) transcription complexes has been investigated by assaying whether pre-assembly of intermediate complexes reduces the extended time required for start-site melting. The results show that a closed complex requiring factors IIA, IID, and the acidic activator GAL4-AH forms in a rate-limiting step. This directs the templates into a productive assembly pathway. Factor TFIIB is then added rapidly, affording further protection against diversion into nonproductive pathways. These events are followed by a series of rapid steps in which the remaining general factors are assembled onto the template, which is then melted using the energy of ATP hydrolysis. PMID- 1516832 TI - StuA is required for cell pattern formation in Aspergillus. AB - The stunted (stuA) gene product is required for the orderly differentiation and spatial organization of cell types of the Aspergillus nidulans conidiophore. Expression of the stuA gene is complex. Two transcripts, stuA alpha and stuA beta, are initiated from separate promoters. Transcription of both RNAs increases approximately 50-fold during the establishment of developmental competence. Induction-dependent transcriptional and post-transcriptional regulatory mechanisms further enhance expression 15-fold. Consistent with the latter observation, both transcripts have structural features characteristic of RNAs subject to translational control. Conidiophore morphogenesis requires regulatory interactions between the products of the stuA, bristle (brlA), and abacus (abaA) genes. Enhanced stunted expression is cell type specific and dependent on a functional BrlA protein. StuA affects the spatial localization of AbaA by acting directly, or indirectly, to repress abaA expression. PMID- 1516831 TI - The Drosophila gene Hairless encodes a novel basic protein that controls alternative cell fates in adult sensory organ development. AB - The mechanosensory bristles of adult Drosophila are composed of four cells that, in most cases, are progeny of a single sensory organ precursor (SOP) cell. Two sister cells in this lineage, the trichogen and tormogen, produce the external shaft and socket of the bristle, respectively. Loss-of-function mutations of Hairless (H) confer two distinct mutant phenotypes on adult bristles. The bristle loss phenotype results from the failure to specify and/or execute the SOP cell fate; the double socket phenotype results from the transformation of the trichogen (shaft) cell into a second tormogen (socket) cell. We have found that the H gene encodes a novel basic protein with a predicted molecular mass of 109 kD. Basal levels of expression of a transgene (P[Hs-H]) in which the H protein coding region is under the control of the Hsp70 promoter are sufficient to provide full rescue of H mutant phenotypes. Heat shock treatment of P[Hs-H] transgenic animals as late larvae and early pupae produces a tormogen-to trichogen (double shaft) cell fate transformation, as well as bristle multiplication and loss phenotypes very similar to those caused by loss-of function mutations in the neurogenic gene Notch. Our results indicate that the SOP cell fate requires H to antagonize the activity of the neurogenic group of genes and that the expression of distinct cell fates by the trichogen/tormogen sister cell pair depends on an asymmetry in their levels of H+ activity or in their thresholds for response to H. PMID- 1516833 TI - Human myocyte-specific enhancer factor 2 comprises a group of tissue-restricted MADS box transcription factors. AB - The MEF2 site is an essential element of muscle enhancers and promoters that is bound by a nuclear activity found, so far, only in muscle and required for tissue specific transcription. We have cloned a group of transcription factors from human muscle that are responsible for this activity: They are present in muscle specific DNA-binding complexes, have a target sequence specificity identical to that of the endogenous activity, and are MEF2 site-dependent transcriptional activators. These MEF2 proteins comprise several alternatively spliced isoforms from one gene and a related factor encoded by a second gene. All share a conserved amino-terminal DNA-binding domain that includes the MADS homology. MEF2 transcripts are ubiquitous but accumulate preferentially in skeletal muscle, heart, and brain. Specific alternatively spliced isoforms are restricted to these tissues, correlating exactly with the presence of endogenous MEF2 activity. Furthermore, MEF2 protein is detected only in skeletal and cardiac muscle nuclei and not in myoblast and nonmuscle cells. Thus, post-transcriptional regulation is important in the generation of tissue-specific MEF2 activity. Cardiac and smooth, as well as skeletal, muscles contain functionally saturating levels of MEF2 trans activating factors that are absent in nonmuscle cells. Moreover, MEF2 is induced in nonmuscle cells by MyoD; however, MEF2 alone is insufficient to produce the full muscle phenotype. Implications for the molecular mechanisms of myogenesis are considered. PMID- 1516834 TI - Yeast GCN4 as a probe for oncogenesis by AP-1 transcription factors: transcriptional activation through AP-1 sites is not sufficient for cellular transformation. AB - The Jun and Fos oncoproteins belong to the AP-1 family of transcriptional activators and are believed to induce cellular transformation by inappropriately activating genes involved in cell replication. To determine whether transcriptional activation through AP-1 sites is sufficient for transforming activity, we examined the properties of an autonomous and heterologous AP-1 protein, yeast GCN4, in rat embryo fibroblasts. GCN4 induces transcriptional activation through AP-1 sites but, unlike Jun and Fos, fails to induce cellular transformation, in cooperation with Ha-ras. Jun-GCN4 and Fos-GCN4 homodimers independently induce cellular transformation indicating that the amino-terminal regions of Jun and Fos each contain regulatory functions that are required for oncogenesis but are distinct from generic transcriptional activation domains. In addition, these observations have implications for the nature of the oncogenically relevant target genes that respond to Jun and Fos. PMID- 1516835 TI - Conserved motifs in Fos and Jun define a new class of activation domain. AB - Fos and Jun form a tight heterodimeric complex that activates transcription by AP1 sites. We have recognized that two adjacent regions of the Jun A1 activation domain are conserved in the Fos protein, and we refer to these two homologous regions as homology box 1 (HOB1) and homology box 2 (HOB2). Using GAL4 chimeras, we show that the HOB1/HOB2 region of Fos and Jun is an independent activation domain in which HOB1 and HOB2 act cooperatively to activate transcription. This cooperativity is retained after the replacement of Fos HOB1 or HOB2 with the equivalent domain of Jun or when duplicated HOB1/HOB1 and HOB2/HOB2 combinations are generated. In the Fos protein, HOB1 or HOB2 can also cooperate with a distinct domain at the carboxyl terminus of the protein. Using the HOB2 consensus sequence as a guide, we identified a HOB2-containing activation domain in the CCAAT/enhancer binding protein (C/EBP) protein. This HOB2 motif can cooperate with as yet undefined sequences in C/EBP and will function even when linked to Jun HOB1. Thus, HOB1 and HOB2 represent inert "cooperating modules" that are combined to generate a functional activation domain. Each of these modules has the potential to cooperate with both distinct and identical domains. The presence of HOB-like modules in three different transcription factors indicates that the HOB motifs characterize a new class of activation domain. These motifs can be used now to identify other transcription factors with such modular characteristics. PMID- 1516836 TI - Lead-induced lipid peroxidation and antioxidant defense components of developing chick embryos. AB - Administration of lead (1.25 and 2.5 mumol/kg egg weight) to 14-day-old chick embryos enhanced the level of lipid peroxides (LPO) in tissues of liver, brain, and heart. Accumulation of LPO was maximum at 9 h after treatment with lead and returned to normal level by 72 h. Further, we have studied the levels of glutathione-S-transferase (GST), glutathione reductase (GR), glutathione peroxidase (GPx), superoxide dismutase (SOD), and catalase. At 9 h posttreatment, the hepatic GR was reduced significantly with the induction of GST and considerable depletion of GSH. However, in brain and heart, both GR and GST activities were unaltered with significant reduction of GSH. Further, an increase of non-Se-dependent GPx and SOD activities were observed in liver, brain, and heart. Similarly, at 72 h, although the GPx activity was found decreased in liver and brain, the GST, catalase, and SOD activities were significantly increased in all the three tissues alike, suggesting tissue-specific changes of antioxidant defense components in response to lead treatment. Our results suggests that the elevated levels of GST, SOD, and catalase at 72 h were successful in bringing LPO levels back to normal. PMID- 1516837 TI - Antioxidant mechanism of Mn(II) in phospholipid peroxidation. AB - Antioxidant action of Mn2+ on radical-mediated lipid peroxidation without added iron in microsomal lipid liposomes and on iron-supported lipid peroxidation in phospholipid liposomes or in microsomes was investigated. High concentrations of Mn2+ above 50 microM inhibited 2,2'-azobis (2-amidinopropane) (ABAP)-supported lipid peroxidation without added iron at the early stage, while upon prolonged incubation, malondialdehyde production was rather enhanced as compared with the control in the absence of Mn2+. However, in a lipid-soluble radical initiator, 2,2'-azobis (2,4-dimethyl-valeronitrile) (AMVN)-supported lipid peroxidation of methyl linoleate in methanol Mn2+ apparently did not scavenge lipid radicals and lipid peroxyl radicals, contrary to a previous report. At concentrations lower than 5 microM, Mn2+ competitively inhibited Fe(2+)-pyrophosphate-supported lipid peroxidation in liposomes consisting of phosphatidylcholine with arachidonic acid at the beta-position and phosphatidylserine dipalmitoyl, and reduced nicotinamide adenine dinucleotide phosphate (NADPH)-supported lipid peroxidation in the presence of iron complex in microsomes. Iron reduction responsible for lipid peroxidation in microsomes was not influenced by Mn2+. PMID- 1516838 TI - 8-Hydroxydeoxyguanosine in vitro: effects of glutathione, ascorbate, and 5 aminosalicylic acid. AB - Oxidative DNA damage, as expressed by 8-hydroxydeoxyguanosine (8-OHdG), was investigated in calf thymus DNA exposed to either ultraviolet radiation or to FeCl2/H2O2 in a Fenton-like reaction. The influence of iron (absent in the UV system and present in the FeCl2/H2O2 system) and pH (7.4 and 4.0) on the effect of glutathione (GSH), ascorbate, and 5-aminosalicylic acid (5-ASA, a drug used in the treatment of chronic inflammatory bowel diseases) was examined in these systems. Without iron, all three compounds considerably reduced 8-OHdG formation (i.e., acted as scavengers), while in the presence of iron salts, 8-OHdG formation was accelerated (except for GSH at pH 7.4), i.e., the compounds acted as prooxidants. This effect was augmented at low pH. The prooxidant property of 5 ASA may have implications for its clinical use. Maximum scavenging effect for all the compounds investigated was obtained at much lower doses than the maximum enhancing effect. This demonstrates that to the end of oxy-radical scavenging, the concentration of the GSH, ascorbate, and 5-ASA, respectively, should be chosen to obtain maximum antioxidant effect and minimum prooxidant effects. The significance of this finding for the selection of antioxidant dose is important but remains to be investigated further. PMID- 1516839 TI - Effects of beta-carotene and alpha-tocopherol on radical-initiated peroxidation of microsomes. AB - Rat liver microsomal membranes were exposed to either beta-nicotinamide adenine dinucleotide phosphate (NADPH), adenosine 5'-diphosphate (ADP), and Fe+3 or to azocompounds, and the antioxidant activities of beta-carotene and alpha tocopherol were studied. Lipid peroxidation was monitored either by malondialdehyde (MDA) formation in the thiobarbituric acid assay at 535 nm or by hydroperoxide formation at 234 nm, after high-pressure liquid chromatography (HPLC) separation of phospholipid hydroperoxides. The radical initiators, water soluble 2,2'-azobis(2-amidinopropane) (AAPH) and lipid-soluble 2,2'-azobis(2,4 dimethylvaleronitrile (AMVN), when thermally decomposed at 37 degrees C under air, produced a constant rate of lipid peroxidation in microsomes and lag times inversely related to their concentrations. Using 25 mM AAPH, beta-carotene suppressed lipid peroxidation at a concentration of 50 nmol/mg protein; using 24 mM AMVN, an inhibition of MDA formation was observed at a concentration of only 5 nmol/mg protein. Inhibition by beta-carotene did not produce a clearly defined lag phase. During AAPH-induced lipid peroxidation, beta-carotene was consumed linearly, and high levels of the antioxidant were still present at the end of 45 min of incubation. Using NADPH/ADP/Fe+3, protection by beta-carotene was observed at 10 nmol/mg protein. alpha-Tocopherol effectively suppressed both MDA and hydroperoxide formation in a dose-dependent manner when either NADPH/ADP/Fe+3 or azocompounds were used. These effects were observed at very low concentrations of the added alpha-tocopherol, ranging from 2 to 3 nmol/mg protein. When the lag times were measurable (AAPH and AMVN), they were directly proportional to the concentration of alpha-tocopherol and revealed the presence of endogenous antioxidants in the microsomal membranes. Different temporal relationships between the loss of alpha-tocopherol and lipid peroxidation were observed in relation to the prooxidant used. A substantial depletion of about 70% of endogenous alpha-tocopherol preceded the propagation phase when induced by the azocompounds, while only 20% of antioxidant disappeared at the beginning of the peroxidation when induced by NADPH/ADP/Fe+3. Although our results show that both beta-carotene and alpha-tocopherol suppress the peroxidation of microsomal membranes, their antioxidant efficacy is influenced by several factors, including the type of radical initiator involved and the site and rate of radical production. PMID- 1516840 TI - Effects of recombinant human extracellular-superoxide dismutase type C on myocardial reperfusion injury in isolated cold-arrested rat hearts. AB - The efficacy of recombinant human extracellular-superoxide dismutase type C (EC SOD C) on myocardial reperfusion injury was explored in hypothermically arrested rat hearts, as was its site of action. Forty isolated working rat hearts were subjected to 30 min of global ischemia followed by 30 min of reperfusion. The hearts were arrested by the administration of 10 mL of cold perfusate at the onset of ischemia. At the same time, they were randomly assigned to one of five groups; A: cold perfusate only; B: cold perfusate + EC-SOD C 10.4 mg/L (30,000 U/L); C: cold perfusate+bovine CuZn-SOD 7.5 mg/L (30,000 U/L); D: cold perfusate + EC-SOD C 10.4 mg/L + heparin 50,000U/L; E: cold perfusate + heparin 50,000 U/L. Heparin was given to prevent binding of EC-SOD C to endothelial cell surfaces. Left ventricular function was studied before ischemia and at the end of reperfusion. Percent recovery of maximal left ventricular dP/dt after reperfusion was more pronounced in group B (109 +/- 24%; p less than .05) than in groups A (42 +/- 40%), C (47 +/- 36%), D (44 +/- 33%) and E (58 +/- 25%). Likewise, percent recovery of the double product (heart rate x systolic left ventricular pressure) was better in group B (104 +/- 18%; p less than .05) than in the other groups (A: 47 +/- 37%, C: 49 +/- 36%, D: 50 +/- 35%, E: 69 +/- 31%). Compared to the preischemic level, creatine kinase increased significantly in the coronary effluent after reperfusion in groups A, C, D, and E, but not in group B. The results suggest that EC-SOD C, which attaches to the endothelial cell surfaces, might be particularly effective as protection against myocardial reperfusion injury when given together with cardioplegic solution. PMID- 1516841 TI - Progressive increases in serum catalase activity in advancing human immunodeficiency virus infection. AB - We found that serum from individuals with Acquired Immunodeficiency Syndrome (AIDS) had more (p less than .05) catalase activity (31.5 +/- 5.2 U/mL) than serum from healthy control subjects (7.3 +/- 0.8 U/mL). Moreover, serum catalase (but not glutathione peroxidase) activity increased progressively with advancing human immunodeficiency virus (HIV) infection (i.e., AIDS greater than symptomatic infection greater than asymptomatic infection greater than controls). Increases in serum catalase activity correlated with increases in serum hydrogen peroxide (H2O2) scavenging ability and reached levels which decreased exogenous H2O2 mediated injury to cultured endothelial cells without altering neutrophil bactericidal activity or mononuclear cell cytotoxicity in vitro. Serum catalase activity correlated with serum lactate dehydrogenase (LDH) activity but did not appear to be a consequence of erythrocyte (RBC) hemolysis since RBC fragility and serum haptoglobin levels were comparable in HIV-infected and control subjects. Increases in serum catalase activity may reflect and/or compensate for systemic glutathione and other antioxidant deficiencies in HIV-infected individuals. PMID- 1516842 TI - Mechanism(s) involved in meat mutagen formation and inhibition. AB - The Maillard reaction, which involves Amadori rearrangement as a key step, also results in sugar fragmentation and free radical formation. The imidazoquinoline meat mutagens (2-amino-3-methylimidazo[4,5-f]-quinoline, or IQ, and 2-amino-3,4 dimethylimidazo[4,5-f]quinoline, or MeIQ) are formed from a reaction mixture containing alkylpyridine free radicals and creatinine. The imidazoquinoxaline meat mutagens (2-amino-3,4-dimethylimidazo[4,5-f]-quinoxaline, or MeIQx, and 2 amino-3,4,8-trimethylimidazo[4,5-f]-quinoxaline, or 4,8-DiMeIQx) may be produced by reacting a mixture containing dialkylpyrazine free radicals and creatinine. Two different pathways for free radical formation are proposed. One involves bimolecular ring formation from the enaminol form of the glycoaldehyde alkylimine and is followed by oxidative formation of the free radical. The other pathway involves formation of N,N1-dialkylpyrazinium ions from glyoxal monoalkylimine followed by reduction to produce the free radicals. The respective intermediates (glycoaldehyde alkylimine and glyoxal monoalkylamine) are formed by reacting glycoaldehyde and glyoxal with amino compounds. The glycoaldehyde system reacts faster and produces more free radicals than the glyoxal system. The reactions help to explain the formation of imidazoquinoxaline meat mutagens and their predominance in fried fish and why these mutagens are present in larger quantities in fried ground beef than the imidazoquinoline-type meat mutagens. These two pathways may not be the only mechanisms involved in formation of meat mutagens, but other free radical reactions may also contribute to meat mutagenicity and are mentioned briefly.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1516843 TI - Antioxidant depletion in aortic crossclamping ischemia: increase of the plasma alpha-tocopheryl quinone/alpha-tocopherol ratio. AB - To assess whether oxidative stress contributes to the ischemia/reperfusion injury of aortic surgery, the contents of alpha-tocopherol, alpha-tocopheryl quinone, ascorbate, lipid-derived malondialdehyde, protein thiols, cholesterol, and lactate were analyzed in plasma samples from 24 patients subjected to aortic crossclamping. alpha-Tocopherol, ascorbate, and protein thiols decreased during ischemia, whereas alpha-tocopheryl quinone increased in all but two cases, doubling on average in proportion to alpha-tocopherol. Upon reperfusion alpha tocopherol, ascorbate, and protein thiols remained low, whereas alpha-tocopheryl quinone returned to the preischemic level. Lipid-derived malondialdehyde (a measure of lipid hydroperoxides) increased significantly only during reperfusion. The results suggest that oxidative stress occurs simultaneously with ischemia/reperfusion during aortic surgery, and that measurement of the tocopheryl quinone/tocopherol ratio may shed new light on the underlying pathological events. PMID- 1516844 TI - Clastogenic and mutagenic actions of active species generated in the 6 hydroxydopamine/oxygen reaction: effects of scavengers of active oxygen, iron, and metal chelating agents. AB - A pro-oxidant triphenol, 6-hydroxydopamine (6-OHDA), induced mutations in the Salmonella typhimurium TA 104 tester strain (over the concentration range to 800 microM), and induced chromosomal aberrations in cultured Chinese hamster ovary (CHO) cells at lower concentrations (up to 90 microM). It was however only marginally mutagenic (up to cytotoxic levels of 200 microM) in the TA102 tester strain. Clastogenicity in the more sensitive CHO cell assay was mediated by activated oxygen. Superoxide dismutase decreased the incidence of chromosomal aberrations by 60% and catalase (or superoxide dismutase plus catalase) decreased the incidence to control levels. The clastogenicity of 6-OHDA was dependent upon unsequestered transition metal ions, since addition of EDTA plus desferrioxamine decreased chromosomal aberrations by 90%. The simplest explanation of the data is that genotoxicity is mediated by active species generated in a Fenton-type reaction between 6-OHDA and H2O2 catalyzed by traces of metals in the medium. PMID- 1516846 TI - Electrochemical characteristics of nitroheterocyclic compounds of biological interest. VIII. Stability of nitro radical anions from cyclic voltammetric studies. AB - The stability of the one electron addition product of four biologically important nitroheterocyclic compounds has been examined electrochemically. Using cyclic voltammetry the tendency of the nitro radical anion to undergo disproportionation was studied by two methods of analysis. The first was based on determining the voltammetric time-constant required for half of the reduction product, RNO2-., to react further. The second concerned the minimum volume of dimethylformamide which had to be added to the aqueous electrolytic medium to give a specific cyclic voltammetric response. Both methods were found to compare well with the results obtained for RNO2-. stabilities using a theoretically derived procedure for a second order reaction following a charge-transfer step. The use of these alternative approaches for quantifying the reactivity of reduction products is discussed. The time-constant method in particular may be useful in studying complex reaction pathways. PMID- 1516845 TI - Antioxidant activity of ubiquinone-3 in human low density lipoprotein. AB - The ability of ubiquinone-3, a short chain ubiquinone homologue, to prevent Cu2+ induced oxidation of human low density lipoprotein was investigated. The results are as follows: in the presence of ubiquinone-3 the extent of peroxidation, as determined by the formation of thiobarbituric acid reactive substances, was only one third of that found in its absence; the quinone can also prevent the fragmentation of apolipoprotein B-100 and the increase of the net negative surface charge of the particle. PMID- 1516847 TI - Mass spectrometric identification of the radical adducts of a fluorescamine derivatized nitroxide. PMID- 1516848 TI - The role of extracellular medium components and specific amino acids in the cytotoxic response of Escherichia coli and Chinese hamster ovary cells to hydrogen peroxide. AB - A concentration of H2O2 resulting in mode one killing of Escherichia coli is more toxic when exposure to the oxidant is performed in complete medium (K medium), as compared to a saline (M9 salts). Inorganic salts (MgSO4 and CaCl2), thiamine or glucose, when added separately, or combined, to M9 salts had no effect on the cytotoxic response to H2O2. In contrast, the lethality of the oxidant was highly dependent on the presence of the amino acids in the incubation medium. The addition of glucose further enhanced this response. Among the seventeen amino acids which are present in the complete amino acid mixture, only two, i.e. L histidine and L-cystine, were found to increase the toxicity of H2O2. Again, glucose augmented this response. The effect of these amino acids on the growth inhibitory action of hydrogen peroxide was also tested in Chinese Hamster Ovary cells. It was found that L-histidine was capable of increasing the toxicity of the oxidant whereas all the other amino acids did not affect the toxicity of the oxidant. Glucose only slightly augmented this effect of L-histidine. DNA single strand breakage produced by H2O2 was increased by L-histidine and was not significantly modified by the other amino acids. DNA double strand breakage was also shown to occur in cells exposed to H2O2-L-histidine, and this effect was independent on the presence of glucose. These results demonstrate that the cytotoxic response of bacterial and mammalian cells to challenge with H2O2 is highly dependent on the composition of the extracellular milieu.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1516849 TI - Control of pro-oxidant activity of cupric ions by entrapment in unilamellar lipid vesicles. AB - As a demonstration of a potential means of delivering and controlling the biochemical and biological activity of metal ions, cupric ions have been trapped in unilamellar phospholipid vesicles. The activity of these cupric ion-containing vesicles as catalysts of the autoxidation of ascorbate and epinephrine has been investigated. A marked increase in autoxidation rate was observed on release of the cupric ion on addition of detergent. When an azobenzene-containing photochromic lipid was incorporated in the bilayer membrane of the vesicles, the release of cupric ions could be initiated by irradiation with ultraviolet light. In the dark, these vesicles remained stable for at least several weeks. Photo controlled release of liposomally-entrapped species might find application in areas similar to those where 'caged' reagents are presently used. PMID- 1516850 TI - Ubisemiquinones of the mitochondrial respiratory chain do not interact with molecular oxygen. AB - The present investigation deals with the suggested role of redox-cycling ubisemiquinones in mitochondrial O2-. generation. Due to the functional complexity of electron-transferring ubiquinones in the respiratory chain, model experiments were designed to study whether ubisemiquinones will directly react with oxygen, thereby generating O2-. radicals. Based on the fact that mitochondrial ubiquinone was reported to operate in an aprotic surrounding of the inner mitochondrial membrane, the reactivity of ubisemiquinones with oxygen was tested in water-free acetonitrile. Our results prove that autoxidation of ubisemiquinones requires the addition of protons to the non-polar reaction system. An experimental evaluation of the validity of this finding with respect to mitochondrial ubiquinones is impeded by the biochemical role that oxygen plays in the establishment of ubisemiquinone populations. To differentiate between a possible direct interaction of oxygen on redox-cycling ubisemiquinones and this indirect biochemical O2 effect, we have successfully introduced ferricyanide instead of oxygen to establish mitochondrial ubisemiquinone pools. Ubisemiquinones in this reaction system were not susceptible to oxygen and no O2 . radicals were released unless the inner mitochondrial membrane was protonated by toluene pretreatment. Since the inner mitochondrial membrane is normally not permeable to protons (which is a prerequisite of the chemiosmotic theory of energy conservation) based on our experiments we can exclude the involvement of redox-cycling ubisemiquinones in mitochondrial O2-. generation. PMID- 1516852 TI - [The status of replantation centers and services in the area served by the German Professional Society of Microsurgery of Peripheral Nerves and Blood Vessels (Commission for Replantation)]. AB - This survey concerns the years 1989 and 1990. While the number of institutions performing replantations remained constant in Austria and Switzerland, there has been a noticeable trend in Germany from around-the-clock replantation centers to simple replantation services, offering emergency microsurgery by arrangement only. The total number of replantations performed decreased from 975 replanted parts (903 microreplantations and 72 macroreplantations) in 1989 to 875 in 1990, with a micro-/macroreplantation ratio of 12.8:1. Based on the results of questionaire received from 34 university and city hospitals in Austria, Switzerland and former West Germany, an analysis of clinical organization and management of replantation services is presented. PMID- 1516851 TI - [Siliconoma and rheumatic symptoms--a familial and a questionable complication of silicone implantation]. AB - Ruptured silicone-gel filled implants after breast augmentation or reconstruction may cause siliconomas. These lesions frequently develop years later and should be surgically excised. Since the use of modern double lumen implants they do not occur anymore. The possibility of a correlation between silicone implants and the incidence of rheumatologic disorders is critically evaluated by case reports from the world literature. Up to now, no statistically significant cumulation of these disorders in women with silicone implants can be observed. PMID- 1516853 TI - Polyotia. A case report. AB - An extremely rare case of polyotia is presented. A seven-month old male had a congenital deformity of the right auricle, appearing like a large accessory auricular appendage. It had a small helix-like protuberance connecting to a very long helical crus; there was a conchal cavity between the external auditory meatus and the protuberance. Surgery led to good results. The surgical procedure is described and the literature concerning polyotia discussed. Our diagnostic criteria for polyotia and the accessory auricular appendage are presented. PMID- 1516854 TI - [Advanced carpal collapse (SLAC-wrist) in scaphoid pseudarthrosis. Therapy concept: medio-carpal partial arthrodesis]. AB - Longstanding unstable scaphoid nonunions inevitably lead to carpal collapse and symptomatic secondary arthrotic changes, ruling out reconstructive procedures to the scaphoid itself. Partial mediocarpal fusion, however, can preserve some wrist motion and markedly reduce or even eliminate wrist pain. By correcting the malalignment of the lunate and capitate, carpal height is restored. By excision of the scaphoid, its destroyed articular surfaces are removed. In 26 of 31 patients undergoing mediocarpal fusion, complete or at least significant reduction of wrist pain was observed. Average grip strength increased by 23%, whereas wrist mobility decreased by 33 to 40% with a relatively short follow-up of 14 months. Total wrist fusion remains the last line of defense. PMID- 1516855 TI - [Indications for and value of kinematography of the wrist joint]. AB - Ruptures of carpal ligaments are frequently overlooked, as they are difficult to diagnose. The authors evaluate 63 wrist kinematographies and include it in their algorithm for the examination of the painful wrist. PMID- 1516856 TI - [Initial experiences with a new wrist joint fixator in treatment of distal radius fractures]. AB - Between January 1989 and October 1991, 56 patients with 57 distal radius fractures were treated with the new Orthofix wrist fixator. This review of 43 patients consists of cases with follow-ups of at least 12 months. One patient had died, and 38 (90.5%) of the remaining 42 fractures were examined 20.3 months after surgery, on average. Radiological findings were classified according to Lidstrom, and the functional results according to Gartland and Werley in the Sarmiento modification. Functional analysis demonstrated excellent and good results in 73% of the fractures. Although the number of cases studied is too small for statistical analysis, the results do show a trend emphasizing the importance of subtle anatomical restoration, particularly of the radial length. Since this cannot always be obtained by external fixation alone, supplementary Kirschner-wires, screws and bone-grafting can be necessary. The main advantages of the new Orthofix fixator are its light-weight design, simple application, and the possibility of fracture reduction even after the device has been mounted. Early mobilisation has not been evaluated sufficiently, so no general recommendations can be made yet. PMID- 1516857 TI - [Mycobacterium malmoense infection of the flexor tendon sheath]. AB - Infections of the tendon sheath caused by non-tuberculous mycobacteria are well known. So far, only one case involving Mycobacterium malmoense has been reported. The authors report of a 73-year old patient having undergone carpal tunnel release. In spite of granulomatous inflammation of the flexor tendon sheaths, there was no biopsy cultured for acid-fast bacteria. One year later, symptoms recurred and synovialectomy was repeated. In spite of macroscopic appearance of the synovialis and histological studies, a specific diagnosis was not yet made. Two weeks later, acid-fast bacteria, identified as M. malmoense were cultured in the BACTEC vial. Because specific treatment was not initiated, a further recurrence developed five months later, necessitating further surgery with synovialectomy. Properly treated with Rifampin and Ethambutal for twelve months, the patient has remained asymptomatic for the following two years. PMID- 1516858 TI - [Modification of the aerobic metabolism of human full skin complexes. An in vitro study]. AB - The effect of increased oxygen supply on oxygen uptake of isolated human full thickness skin grafts was investigated. Acute hyperoxic conditions led to temporary slight reductions of the cellular oxygen consumption rate, whereas pronounced longer-lasting effects could not be demonstrated. It was concluded that hyperoxic intervention is not suitable to compensate for the complex metabolic disorders arising in transplanted tissue. PMID- 1516859 TI - [Medical aspects and structural implications of cholinesterase inhibitors]. PMID- 1516860 TI - [The trimolecular complex as a target for specific immunotherapy in experimental autoimmune encephalomyelitis--applications for multiple sclerosis and other human autoimmune disease]. PMID- 1516861 TI - [Radiosurgery]. PMID- 1516862 TI - [Surgical management of posttraumatic malignant brain edema--a historical review]. PMID- 1516863 TI - [Therapeutic approach after first epileptic attack in children]. PMID- 1516864 TI - [Sarcoma botryoides of the uterine cervix--current therapeutic approach]. PMID- 1516865 TI - [Treatment of malignant diseases with synthetic oligonucleotides]. PMID- 1516866 TI - [Treatment with potassium iodide following nuclear reactor accident]. PMID- 1516867 TI - [History of diabetes mellitus]. PMID- 1516868 TI - [Body injuries in musicians]. PMID- 1516870 TI - [Influence of muscle tone and force on ossification in postcomatose patients]. AB - 68 post-traumatic brain-injured patients in postcomatose unawareness (PCU) states were admitted during 1982-1987. 32 of them also suffered from fractures of the long bones and pelvis (total of 51 limbs). The muscle tone and force of all limbs were examined and x-rays of the large joints and of the fractures were taken periodically. Periarticular new-bone formation appeared in 32 patients. Normal callus developed in 41 fractured limbs and hypertrophic callus in 18. We found that pathological muscular tone (hypertonus and hypotonus) and pathologically decreased muscle force (paresis and plegia) were closely correlated with the appearance of periarticular new-bone formation. The extent of callus formation was not correlated with muscle tone and force. PMID- 1516869 TI - [Prevalence of eating disorders among female Israel defence force recruits]. AB - It is assumed that the incidence of anorexia nervosa and bulimia nervosa in the general population has been increasing. Medical personnel in the IDF also believe this to be true with regard to their female soldiers. We administered the eating attitude test (EAT) to 1112 female soldiers at the beginning of their military service and determined weight and height for each. Those whose EAT scores were high or whose weights were low were then interviewed by the study psychiatrist and the author. 2 of them (0.2%) were found to be suffering from anorexia nervosa. Both were identified by their low weights; their EAT scores were both normal. 27 (2.4%) were diagnosed as having a partial eating disorder syndrome, in a third of whom it was severe. The severe cases were also identified by their weights and not by EAT scores. In addition, 4 (0.5%) had bulimia nervosa, all of whom were identified from their EAT scores. These findings are similar to those of some of the most recent studies in the field. The deficiencies of the EAT scale were more apparent in this than in other studies. Because of its relatively low PPV as well as the apparent reluctance of many subjects to answer truthfully, the scale is not effective by itself for screening purposes. As was shown in this study, measuring weight and height in addition considerably improved accuracy of screening. PMID- 1516871 TI - [Atrial septal defects and embolic stroke in young adults]. AB - The mechanism of embolic stroke in young adults remains unidentified in about 35% of cases. In recent years defects in the atrial septum have been described as an important route for cerebral and retinal embolism. These include classical atrial septal defect and patent foramen ovale, as well as the less well-recognized entity of atrial septal aneurysm, with or without interatrial communication. The combined incidence of these defects in the general population is between 20-35%. The introduction of transesophageal echocardiography and the use of echogenic contrast have lead to significant improvement in identification. We describe 3 patients in whom atrial defects were identified as possible routes for cerebral embolism: The first presented with recurrent stroke and combined atrial septal aneurysm and patent foramen ovale. In the second, patent foramen ovale was found in a patient with 2 prosthetic values. The third was a soldier in whom patent foramen ovale was found following transient loss of consciousness. Based on our modest experience and review of the literature we believe that transesophageal and contrast echocardiography should be performed in every young patient with unexplained cerebral ischemia. PMID- 1516872 TI - [Ascaris lumbricoides--a cause of acute abdomen]. AB - Ascaris lumbricoides infestation is the most common helminthic disease in many developing countries and may cause severe surgical complications, especially in children. We present a 3-year-old Ethiopian immigrant brought to hospital directly from the airport because of signs of acute abdomen. It was found to be caused by volvulus and necrosis of a loop of bowel impacted with worms. The necrotic bowel loop was resected and a temporary ileostomy was formed; recovery was uneventful. This disease and its severe complications are rare in Israel and the western world. Awareness of its occurrence is important in view of the present world-wide large-scale immigration from developing countries. PMID- 1516873 TI - [Traumatic rupture of the diaphragm in an infant]. AB - Traumatic rupture of the diaphragm can be caused by both penetrating and blunt trauma. High kinetic energy applied to the abdomen during blunt abdominal trauma creates pressure differences between the abdominal and chest cavities. These sudden changes in pressure rupture the diaphragm. We present a 13-month-old infant admitted after being injured by a car. In addition to rupture of the diaphragm there were pelvic fractures. Chest x-ray on admission was diagnostic for diaphragmatic rupture. The possibility of congenital diaphragmatic hernia was rejected because of increasing ventilatory embarrassment. PMID- 1516874 TI - [Training pulse recording--useful or superfluous?]. AB - PROBLEM: The setting of an exercise pulse rate has become established in particular in the field of post-infarction rehabilitation. The conditions associated with its establishment, however, vary considerably. As a rule, no differentiation is made for the variations in the muscular work done. OWN STUDIES: Follow-up examinations in 29 post-infarction patients showed that the recommended exercise pulse rate was an average of 10 to 20 beats lower than that established in our office under ergometric conditions. Loading-control via respiration, monitored by lactate measurement, in contrast, has proved superior in our patients, since the respiration is perceived continuously and directly by the patient himself, and is largely independent of the type of exercise involved. CONCLUSIONS: Control of physical exercise (loading) via the respiration would appear superior to that by the measurement of the pulse rate. The setting of an exercise pulse rate only if it can be monitored reliably and continuously with the aid of a measuring device. PMID- 1516875 TI - [The 1990 Bochum cholesterol and blood screening program. Incidence and degree of treatment of cardiovascular risk factors]. AB - STUDY: Over a four-week period, 1,454 inhabitants of the town of Bochum (567 men = 39%, 887 women = 61%) were screened for cardiovascular risk factors. The sample was recruited from voluntary participants, two-thirds of whom were aged between 50 and 69. RESULTS: Age-adjusted mean total plasma cholesterol levels were 223 mg/dl for women, and 218 mg/dl for men. Age-adjusted mean systolic blood pressure were 136.7 mmHg for women, and 140.8 mmHg for men. The corresponding diastolic levels were 85.0 mmHg for women and 87.8 mmHg for men. The prevalence of hypercholesterolemia (greater than or equal to 250 mg/dl) was 32.8%, that of hypertension (greater than or equal to 160/95 mmHg) was 32.7%. Age- and sex specific mean figures and prevalences were lower for total cholesterol and markedly higher for blood pressure as compared with representative German studies. Previously unknown hypertension (greater than or equal to 160 mmHg systolic and/or greater than or equal to 95 mmHg diastolic) was detected in 10%, and hypercholesterolemia (total cholesterol greater than or equal to 250 mgdl) in 16%. A reply postcard was received from the family doctors of only 11% of participants with elevated levels. This means that the follow-up rate remained far below the hoped-for level. CONCLUSIONS: Population screening can be useful in promoting primary and secondary cardiovascular disease by alerting the population to classical risk factors and informing participants about their own personal situation. In order to motivate individuals with high risk factors to act upon this information, screening should be associated with follow-up. PMID- 1516876 TI - [Ambulatory surgery. Part 2: Local anesthesia: contraindications and complications]. PMID- 1516877 TI - [Treatment of chronic hepatitis B. Part 2: Effect of glycyrrhizic acid on the course of illness]. AB - AIMS: Testing of the therapeutic efficacy of Remefa S, a pharmaceutical comprising glycyrrhizinic acid, the major active substance of licorice, on the evolution of the disease in late chronic viral hepatitis B. METHODS: Prospective evaluation of the biochemical, virus-serological and histomorphological data (blind liver aspiration, laparoscopy) during and following 12 months of application (three times a week, short infusions) of Remefa S, and comparison with the course of the disease (12 months) prior to treatment. PATIENTS: Intermediate report on an ongoing multicentre study begun in 1989, with evaluation of 7 subjects receiving the preparation and 3 controls after 12 months of treatment and 10 months of follow-up. RESULTS: During or after treatment, 4 patients experienced a regression of biochemical disease activity. In 2 of the 4 patients, during treatment, an HBe-Ag seroconversion occurred for the first time and has persisted (to date 10 months); in another patient with no detectable HBe Ag prior to treatment, HBe antibodies were formed under treatment, and have persisted to the present time. In 2 of these responders, histology also revealed an unequivocal reduction in disease activity. In contrast, HBs-Ag seroconversion was observed in none of the patients treated. Since in these three patients the virus genome was already integrated within the chromosome of the host cell (hybridization), this had not been expected from the start. CONCLUSIONS: Intravenous chronic application (12 months) of glycyrrhizinic acid in the form of Remefa S in patients with chronic viral hepatitis B, is capable of exercising a positive effect on the evolution of the disease. On the basis of the results obtained so far (30-40% success rate), a comparison with the results obtained with interferon suggests itself. PMID- 1516878 TI - [Anachronistic thinking delays timely diabetic care. K. P. Ratzmann reveals his perspective of ambulatory care. Interview by Wilma Mahler]. PMID- 1516879 TI - [AIDS. Early diagnosis of prenatal HIV infections by IgA?]. PMID- 1516880 TI - [Anxiety disorders--syndrome, personality and relationships. Results of multi methodology diagnosis]. AB - Patients attending the Polyclinic of the Psychiatry Department of the Ludwig Maximilian University in Munich for ambulatory examination and counseling because of panic anxiety states with agoraphobia, were investigated using methods of descriptive-phenomenological diagnostic evaluation of syndromes and personality (structured clinical interviews on the basis of DSM III Criteria) and with methods of empirical married couple and family diagnostic evaluation (Giessen Paar-Test, Family-Assessment-Measure). On the basis of the findings established on three different observational planes--syndrome, personality and inter-personal relationships--it was shown that anxiety disorders are expressed not merely in the symptomatology (panic disorders) and the behavior (e.g. agoraphobia) of the patient; rather, evidence of co-morbidity involving (concomitant?) personality disorders was found in almost 50% of the patients investigated. In comparison with non-clinical control groups, the patients and their partners also indicated considerable disorders in the emotive field and in their affective relationships and contact with others. PMID- 1516881 TI - [Need for intensive disability care. Part 3: Classification of nursing care stages--relation to time requirements]. AB - The proviso "a requirement for constant intensive care" in almost all "care requirement situations" is an extremely strict criterion. It may even exclude some people with an extremely urgent need of care--for example if some of these situations completely fail to apply. In practice, a less strict criterion needs to be applied if the intended sociopolitical aims are to be achieved. On the basis of our experience of the actual situation presenting, orientation to the time-requirement for the services needed in the individual case is recommended as the basis for an assessment of Schwerpflegebedurftigkeit. A minimum requirement of a daily "bodily" care need of about two hours would appear to be necessary. However, an analysis of time requirement must be supplemented by an evaluation of the overall situation. PMID- 1516882 TI - [Ambulatory surgery. Part 3: Diffuse and localized nonspecific infections- phlegmon and abscess]. PMID- 1516884 TI - Alloxan diabetes blocks noradrenergic tachyphylaxis in the isolated rabbit kidney -effects of insulin. AB - Normal and alloxan treated diabetic rabbit kidneys were perfused with Krebs Henseleit solution in a non-recirculating system and the effects of norepinephrine (NOR) 10(-6)M were tested by infusion of this drug for three subsequent periods of 20 min each, with an interval of 10 min for drug wash-out. In the control kidneys the infusion of NOR promoted an intense vasoconstriction, which was less intense during the second and the third periods. This was known as tachyphylaxis. In contrast to the controls, kidneys from diabetic animals did not show tachyphylaxis to NOR, but when insulin was added to the perfusate, tachyphylaxis appeared. Normal kidneys perfused with hyperosmolar solutions show, as in controls, the same phenomenon. The data presented here demonstrate a defect of adrenergic vascular receptors in alloxan treated kidneys, which can be acutely reversed by insulin. These facts are of importance for the understanding of the vascular disease in diabetes. PMID- 1516883 TI - Effect of probucol on recovery from streptozotocin diabetes in rats. AB - The present study was conducted to see the effect of probucol on streptozotocin diabetes in rats. After 2 weeks of a 1% probucol diet, 35 or 50 mg/kg of streptozotocin were intravenously injected into male Wistar rats. All the rats became diabetic 2 days after treatment. Thereafter, in order to see the effect of probucol on spontaneous recovery from streptozotocin diabetes, 25 mg/kg of streptozotocin was injected into rats after two weeks of probucol diet and the diet was continued for additional two weeks. All the rats with a standard diet (group CS, n = 13) and 12 of 13 rats with probucol diet (group PS) became diabetic 2 days after streptozotocin injection. One rate from group PS did not develop diabetes. Two weeks after injection, only 4 of 13 rats in groups CS showed recovery, while 11 of 12 rats in group PS showed recovery from streptozotocin diabetes (p less than 0.05). The average blood glucose levels in group PS were significantly lower than group CS (10.5 +/- 4.6 vs 18.5 +/- 0.6 mM, p less than 0.05). In addition, the pancreatic insulin content of group PS was 8 times greater than that of group CS (0.75 +/- 0.24 vs 0.09 +/- 0.03 mmol/pancreas, p less than 0.01). Thus, the in vivo diabetogenic action of streptozotocin could not be reduced by pretreatment with probucol. However, recovery from streptozotocin diabetes was induced by subsequent treatment with probucol. The precise mechanisms for this phenomenon were not known; but the present findings suggest the protective effect of probucol on beta-cell damage induced by small dose of streptozotocin. PMID- 1516885 TI - "In vitro" effects of insulin on the PDH complex of the isolated perfused heart of rats fed a sucrose-rich diet. AB - We have recently reported that the "in situ" myocardial concentrations of the active form of the Pyruvate Dehydrogenase Complex (PDHa) were significantly decreased in hearts obtained from normal rats fed for 3 weeks on an isocaloric sucrose rich (63%) diet (SRD) when compared to age matched controls fed on the standard laboratory chow (STD). Since, on the one hand SRD rats present glucose intolerance and impaired "in vivo" insulin action and, on the other hand the effects of insulin on the interconversion of heart PDH remains a controversial matter, we found it relevant to study the effects of insulin on the PDH complex in the "in vitro" perfused (Langendorff technique) heart preparations obtained from SRD rats. After a 35 minute perfusion period with 5.5 mM glucose as the only nutrient in the perfusate, PDHa as a percentage of total PDH was found to remain significantly lower in SRD hearts (M +/- SEM 32.6 +/- 2.3) when compared to STD hearts (68.3 +/- 4.6, P less than 0.05) in spite of comparable total PDH activities in both groups of animals. Although the addition of insulin to the perfusate (20 mu/ml) resulted in a significant increase in the percentage of PDHa (45.8 +/- 3.4) of SRD heart, values attained still remained significantly lower than those obtained in STD controls (67.5 +/- 3.6; P less than 0.05). Simultaneously, the addition of insulin to the perfusate, significantly reduced the Acetyl-CoA/CoASH ratio in SRD hearts although this ratio remained still much higher than those observed in STD controls under the same experimental conditions. PMID- 1516886 TI - Suppression of thyroid cell growth by serum IgG in Graves' disease. AB - To determine whether serum immunoglobulin in addition to epidermal growth factor (EGF) augment growth in human thyroid cells, effects of these factors on thyrocytes were tested using IgG derived from 34 patients with Graves' disease and 12 normal subjects. The cell growth was estimated by [3H]-thymidine uptake, cell cycle determined by FACS analysis and the expression of c-fos mRNA in monolayer thyrocytes enzymatically prepared from Graves' thyroid. The addition of IgG taken from patients with Graves' disease inhibited the [3H]-thymidine uptake compared to that taken from control subjects. IgG taken from Graves' disease suppressed EGF-induced increase of S + G2/M phase in cell cycle and the expression of c-fos mRNA, while those taken from normal subjects did not affect at all. [3H]-thymidine uptake was more suppressed by IgG from patients with a smaller-sized goiter than by those with a larger-sized one. There was a negative correlation between the suppression of [3H]-thymidine uptake and levels of TBII (p less than 0.05). There was no correlation between the degree of suppression and the levels of T3, T4, TSAb, TSBAb or MCHA. Thus, in conclusion, IgG derived from sera of Graves' may inhibit the growth of Graves' thyrocytes, leading to the determination of the goiter size. PMID- 1516887 TI - 3,5-T2 stimulates oxygen consumption, but not glucose uptake in human mononuclear blood cells. AB - L-thyroxine (T4), L-triiodothyronine (T3) and 3,5-di-iodothyronine (T2) rapidly (within 30 min) stimulated oxygen consumption in human mononuclear blood cells, whereas the D isomers of T4 and T3 and Triac had no stimulatory effect. Oxygen consumption was stimulated by the same magnitude by equimolar concentrations (5 500 nmol/l) of L-T4, L-T3 and 3,5-T2 reaching a plateau at 100 nmol/l of 0.025 umol/mg DNA x h. The stimulatory effects of T4 and T3, but not of T2 were inhibited by PTU. Glucose uptake was stimulated only by L-T4 and L-T3, whereas 3,5-T2, Triac and the D-isomers of T4 and T3 had no effect. The dose response curve reached an apparent maximum at 100 nmol/l of 0.30 mmol/l x mg DNA x h and PTU had no effect on iodothyronine stimulated glucose uptake. We conclude that 3,5-T2 is a significant intracellular stimulator of oxygen consumption, whereas T3 and T4 stimulate glucose uptake. PMID- 1516888 TI - Electrophysiological changes of Sertoli cells produced by the acute administration of amino acid and FSH. AB - Electrophysiological studies were carried out using seminiferous tubules of "Sertoli cell enriched testes" of rats irradiated in utero. Sertoli cells were inserted with glass microelectrodes in a superfusion chamber continuously perfused with KRb buffer. The topical application of FSH (4.0 mU/ml) produced a biphasic effect characterized by a rapid hyperpolarization (less than 3 s) followed by depolarization. The depolarizing effect of FSH was prolonged and potentiated in the presence of 5 mmol/l alpha-methylamino-isobutyric acid in the bath medium of the superfusion chamber. Verapamil, at a dose (250 mumol/l) that nullified the stimulatory action of FSH in the amino acid transport, suppressed the depolarizing effect of FSH. It was concluded that in immature rat testes FSH produces electrophysiological changes that mediate the stimulatory action of the amino acid transport. PMID- 1516889 TI - The effect of the somatostatin analogue octreotide on growth hormone secretion in insulin-dependent diabetics without residual insulin secretion. AB - Growth hormone (GH) hypersecretion is well documented in insulin-dependent diabetes mellitus (IDDM). Somatostatin inhibits GH in acromegalics and healthy subjects although data on its inhibitory effects on high GH levels in IDDM patients are controversial. The effect of treatment with the somatostatin analogue octreotide ("Sandostatin") on GH secretion, IGF1 levels and metabolic control was investigated in insulin-dependent diabetics. Growth hormone and blood glucose were measured at hourly intervals whilst IGF-I was measured every 6 hours during the 24-h period before and after 7 days' treatment with octreotide (200 micrograms subcutaneously three times daily) in 10 C-peptide negative diabetics. Octreotide significantly reduced mean 24 h GH profile (7.2 +/- 0.7 mU/L before; 5.2 +/- 0.5 mU/L on octreotide, p less than 0.01), IGF-I levels (0.62 +/- 0.06 before; 0.47 +/- 0.05 on octreotide, p less than 0.005) mean 24 h blood glucose (14.4 +/- 0.5 mmol/L before; 12.6 +/- 0.4 mmol/L on octreotide, p less than 0.001) and daily insulin requirements (44.8 +/- 3.0 IU before; 37.2 +/- 3.0 IU on octreotide, p less than 0.02). The shape of 24 h GH profile curve changed significantly on octreotide treatment (p less than 0.05) when it consisted of three nadirs and three peaks closely linked with the time of octreotide administration. Moderate (abdominal discomfort) to severe hypoglycaemia) transient side effects have been observed in all treated patients. The results of this study showed that short-term treatment with octreotide given s. c. every eight hours modulates the pattern of GH secretion in C-peptide negative insulin dependent patients.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1516890 TI - Effect of deflazacort on growth hormone response to insulin tolerance test. AB - Deflazacort (DF) has been claimed to be provided with a reduced distribution into the central nervous system, therefore it is conceivable that this glucocorticoid holds a lower inhibitory effect on GH secretion. To test this hypothesis we studied the GH response to insulin tolerance test (ITT) in two matched groups of patients given equivalent doses of DF and prednisone (PN). The serum glucose changes induced by ITT were similar in the two groups and in control subjects; the mean increase in plasma GH, in particular the peak and the area under the curve (delta AUC), were not different in control subjects and DF-treated patients (25 +/- 12.5 ng/ml and 1790 +/- 904 ng/ml/min versus 27.7 +/- 21.5 ng/ml and 1578 +/- 1242 ng/ml/min) but were significantly reduced in PN-treated patients (8.8 +/ 9.7 ng/ml and 431.6 +/- 451 ng/ml/min). Our study demonstrates that DF does not interfere with the GH response to ITT as PN does. PMID- 1516892 TI - Amplitude smoothing and phase shifting effect of the isolated perfused rat liver on oscillating insulin and glucagon. PMID- 1516891 TI - Relationship between the changes in placental blood flow resistance assessed by Doppler technique and maternal serum placental aminopeptidases, which degrade vaso-active peptides, in pre-eclampsia. AB - Our study showed that there were statistically significant correlations between the systolic and diastolic ratio (S/D) of maternal uterine or umbilical artery and the levels of maternal serum aminopeptidase activities in pre-eclampsia. Kininase I was positively correlated with the S/D ratios, whereas placental leucine aminopeptidase (P-LAP) and aminopeptidase A were negatively correlated with the S/D ratios. It is known that the increased S/D ratios reflect the increased utero-placental blood flow resistance. Since our previous study showed that placental aminopeptidases degrade vasoactive peptides such as oxytocin, angiotensin and bradykinin, which the fetus actively produces, our present study suggests that the increased vascular resistance in feto-placental circulation in pre-eclampsia is partly controlled by changes in vaso-active peptides, via degradation by placental aminopeptidases. PMID- 1516893 TI - Increase of beta-endorphin serum levels by human corticotropin-releasing factor does not affect beta-cell function in overweight women. PMID- 1516894 TI - Is it time for a moratorium on deinstitutionalization? PMID- 1516895 TI - Sertraline: a new serotonergic antidepressant. PMID- 1516896 TI - A social work agenda in psychopharmacology. PMID- 1516897 TI - Neuropsychiatric disorders associated with cocaine use. PMID- 1516898 TI - Memories and murder. PMID- 1516899 TI - Obsessive-compulsive disorder. AB - Obsessive-compulsive disorder is a well-defined clinical syndrome that has been difficult to treat with standard psychotherapies and medications. Data accumulated over the last decade have demonstrated that the disorder is relatively common and frequently coexists with phobia, depression, and alcohol abuse. The authors review current studies of the spectrum of obsessive-compulsive disorder and related disorders that respond to the new serotonergic antidepressants and behavioral therapy. Differential diagnosis, epidemiology and comorbidity, etiology, evaluation, and psychologic and pharmacologic treatments are discussed. Most patients with obsessive-compulsive disorder require long-term treatment with drugs, but behavioral therapy has also been used successfully. Serotonin reuptake inhibitors used in the treatment of depression have been found effective; clomipramine has produced the best results in large-scale tests. The fact that serotonin reuptake inhibitors are effective as both antidepressants and antiobsessional agents suggests common biological factors in disorders that respond to these drugs. PMID- 1516900 TI - Clinical review of clozapine treatment in a state hospital. AB - Medical records of the first 37 patients to begin clozapine treatment at a state hospital in Oregon were reviewed for six months before clozapine treatment and six months after. Patients had a long history of schizophrenia and had responded poorly to antipsychotic medication. Clozapine treatment was generally well tolerated, although the rate of seizures (8 percent) was slightly higher than expected. Psychotic symptoms decreased as measured by the Brief Psychiatric Rating Scale, as did symptoms of tardive dyskinesia as measured by the Abnormal Involuntary Movement Scale. Thirty-four patients remained hospitalized after six months of treatment. However, indicators of social function (hospital privilege level, community passes, violent episodes, and episodes of seclusion and restraint) all showed that patients improved markedly after receiving clozapine. PMID- 1516901 TI - Factors predicting referral to inpatient or outpatient treatment from psychiatric emergency services. AB - Dispositional decisions in ten psychiatric emergency rooms in New York State were examined using logistic regression. Variables influencing recommendations for inpatient or outpatient psychiatric treatment were fairly consistent across the hospitals. All terms used in the regression model were interactions formed from five variables: dangerous behavior as a reason for referral, severity of the mental disorder, the hospital where the patient presented, current signs of psychosis, and a diagnosis of major mental illness. A sixth variable, assaultive behavior in the emergency room, also influenced disposition decisions but could not be considered in the model because all patients with that characteristic were referred for inpatient treatment. A model of disposition decisions based on interactions of variables may be especially powerful because it captures the dynamic combination of factors clinicians encounter. PMID- 1516902 TI - A survey of university-prison collaboration and computerized tracking systems in prisons. AB - It is conservatively estimated that 8 percent of inmates in U.S. prisons have significant psychiatric impairment. Correctional mental health systems are often unable to provide adequate treatment to such inmates because of staff recruitment problems. Collaboration between universities and departments of corrections can help solve recruitment problems, and needs assessment studies and computerized tracking systems can help obtain needed resources. A national survey collected data on collaborations between universities and corrections departments and on needs assessment and computerized tracking systems in prisons. Results indicated that such collaborations exist in more than half of state prison systems. Of 42 states responding, only ten states reported having systemwide computerized tracking systems, but others are in the process of developing such systems. Two thirds of the correctional mental health systems did not have an ongoing needs assessment program. PMID- 1516903 TI - A review of indications for routine EEG in clinical psychiatry. AB - With increasing recognition of the role of organic factors in the etiology of psychiatric disorders, greater use of neurodiagnostic tests is expected. Clinical electroencephalography (EEG) is a noninvasive, low-cost neurodiagnostic technique widely available in psychiatric hospitals. Based on a review of the literature, the author outlines clinical applications of routine (non-computerized) EEG related to evaluation of organic etiologies and symptoms of dementia, delirium, and lithium toxicity; evaluation before electroconvulsive therapy; and routine screening of patients. Screening EEGs are not recommended in settings in which complete neurological examinations are routinely performed. PMID- 1516904 TI - A single-case-study method for treating resistiveness in patients with Alzheimer's disease. AB - A single-case-study approach was used to identify the best medication for treating resistiveness to care in patients with moderately advanced dementia. The double-blind research design incorporated three medications, placebo washout periods, multiple baselines, frequent ratings by nurses of patients' resistiveness, and visual and statistical analysis of results to find the optimal drug, one that provided a stable response at a low dose. Six patients completed the trials. Thiothixene was more effective than oxazepam and diphenhydramine. Important features of the design were its avoidance of polypharmacy and high doses and its use of frequent ratings (each nursing shift) of patients' resistiveness. Although the single-case-study method is labor intensive, it can be beneficial when adapted for clinical use. PMID- 1516905 TI - Primary health care in the CMHC: a role for the nurse practitioner. AB - Although persons with chronic mental illness have a high incidence of physical health problems, they are often ill equipped to seek care within complex health care systems and tend to depend on community mental health centers as their only source of regular health care. The authors describe a role for the nurse practitioner in assessing the medical needs of chronic mentally ill outpatients at a community mental health center and in devising strategies to meet those needs. The nurse practitioner's activities include direct physical health screening and treatment, referral for specialized medical services, consultation, research, and staff and patient education. PMID- 1516906 TI - Intentional hyperventilation as a self-stimulating addiction. PMID- 1516907 TI - Comorbid mental disorders in patients with AMA discharges from alcoholism treatment. PMID- 1516908 TI - A didactic group program for persons found unfit to stand trial. PMID- 1516909 TI - Knowledge about and risk factors for AIDS in a day hospital population. PMID- 1516910 TI - Seroprevalence of HIV and risk factors for AIDS in psychiatric inpatients. PMID- 1516911 TI - Therapeutic benefits of interest-based mediation. PMID- 1516912 TI - Radio psychiatry and community mental health. PMID- 1516913 TI - Partial hospitalization. PMID- 1516914 TI - Partial hospitalization. PMID- 1516915 TI - Dr. Pinheiro's views. PMID- 1516916 TI - Data watch. Survey tracks demand for top heart disease tests. PMID- 1516917 TI - New path. Today's executive career path: new realities, responsibilities for hospitals. AB - There may have been a time when hospital CEOs could promote executive advancement simply by hiring the most talented individuals who walked through their doors. But the world has changed, and a variety of factors, including fewer opportunities for advancement and greater work-force diversity, are compelling CEOs and boards to think carefully and strategically about the issue. PMID- 1516918 TI - Updated emergency departments stress improved access to care. PMID- 1516919 TI - Survey: equipment budgets up; use in outpatient areas growing. AB - Most hospitals increased their capital equipment budgets this year, finds a new survey sponsored by Hospitals and the Linc Group Inc. Rather than adding new services, hospitals are replacing equipment. But they remain cautious about adding new services, experts note. PMID- 1516920 TI - Telecommunications. Hospitals explore new electronic links to reduce costs, increase access. PMID- 1516921 TI - CEOs confuse roles of physician trustees. AB - A majority of hospital CEOs believe physician trustees on their boards tend to represent their medical staffs. But experts warn that CEOs must make certain that their physician trustees represent the community as a whole. PMID- 1516922 TI - A hospital's teamwork and CQI advance shared vision, interdependence among top managers. Interview by Paula Eubanks. AB - As quality improvement programs are initiated in growing numbers of hospitals, senior executives in those hospitals find themselves addressing a range of issues: team building, leadership and interpersonal interaction. CEO Jim Biltz and nurse executive Linda Mild of 760-bed HCA Wesley Medical Center, Wichita, KS, tell Hospitals Staff Editor Paula Eubanks how their participative management style and the hospital's continuous quality improvement (CQI) initiative have fostered new levels of teamwork and shared vision among the institution's top managers. PMID- 1516923 TI - AIDS and the politics of compassion. AB - The AIDS epidemic presents the health care community with an exceptionally complex set of challenges, says June E. Osborn, M.D., the chairwoman of the National Commission on AIDS. Care-giver burnout, clinical and cost issues, and above all the challenge the disease poses to health care provider--and societal- compassion, make this epidemic unusually difficult to tackle, she writes. PMID- 1516924 TI - Macro-orchidism: light and electron microscopic study of four cases. AB - A hormonal and quantitative light microscopy study of one man with macro orchidism associated with mental retardation and fragile X chromosome (case no. 1) and three men with idiopathic macro-orchidism (cases no. 2 to 4) is reported. Hormonal study revealed slightly increased follicle-stimulating hormone serum levels in cases no. 1 to 3. The testes from cases no. 1 (orchidoepididymoectomy specimen) and 2 (testicular biopsy) presented interstitial edema and three different tubular patterns that were arranged in a mosaic-like manner. Type I tubules had an increased diameter (less than 220 microns), dilated lumen, and thin seminiferous epithelium usually consisting of Sertoli cells, spermatogonia, primary spermatocytes, and sometimes a few spermatids. Type II tubules had a normal diameter (180 to 220 microns) and germ cell development varied between complete spermatogenesis and Sertoli-cell-only tubules. Type III tubules had decreased diameter (less than 180 microns), atrophic seminiferous epithelium, and thickened tunica propria. The appearance of the nuclei of the Sertoli cells in the three types of tubules could be either mature or immature. Some of the mature Sertoli cells presented a granular cytoplasm. A few of these granular cells grouped together, forming nests that protruded into the tubular lumen. The testicular biopsies from cases no. 3 and 4 only presented type II tubules that contained both mature and immature Sertoli cells. Quantitative study revealed that the large testicular size was principally due to an increased tubular length in all four cases. Although the seminiferous tubule lesions and interstitial edema suggest an obstructive process, the testicular excretory ducts (studied in case no. 1) appeared normal or only slightly dilated. It is possible that the seminiferous tubule lesions (dilated lumen and germ cell depletion) might be secondary to the Sertoli cell lesions (granular cytoplasm and nuclear immature like pattern. PMID- 1516925 TI - DNA cytometry in postirradiation cervical-vaginal smears. AB - Benign radiation change (BRC) in cervical-vaginal smears may be difficult to distinguish from postirradiation dysplasia (PRD) or recurrent cervical carcinoma. The utility of DNA analysis in postirradiation smears was evaluated retrospectively in 71 patients. Representative Papanicolaou smears were restained with a Feulgen method and 100 to 250 cells were analyzed for DNA content using the CAS 200 image analysis system. Thirty-three control irradiated patients had negative smears with a minimum 3-year follow-up. Thirty controls (91%) had diploid histograms with a mean coefficient of variation of 8.2% and an average of 6.8% of cells in S and G2/M phase. Three control patients had atypical nondiagnostic histograms. Twenty-three patients had abnormal smears and subsequent local recurrence; 21 (91%) had abnormal histograms, with seven showing polyploidy and 14 showing aneuploidy. The remaining 15 patients had abnormal smears diagnosed as PRD but no evidence of recurrent carcinoma. Five were polyploid, six were aneuploid, one was diploid, and three were atypical but nondiagnostic. Interactive DNA cytometry is useful in differentiating BRC from PRD and recurrent cancer. Aneuploidy is rarely, if ever, seen in negative smears with BRC. However, BRC may be associated with broad diploid peaks and increased proliferating cells. An abnormal histogram can be seen with PRD and does not always correlate with recurrent disease. PMID- 1516926 TI - A quantitative approach to the classification of hypospermatogenesis in testicular biopsies for infertility. AB - Absolute counts of germ cells were performed in 110 testicular biopsy specimens from 59 patients with either idiopathic infertility or varicocele and in a series of five autopsy specimens from age-matched controls. The tubular diameter, thickness of the tubular wall, and density of Leydig cells were measured. The following patterns were identified by germ-cell counts in the biopsy specimens: normal cell population, mild decrease in germ cells with normal ratio of cell types, advanced hypospermatogenesis with abnormal ratio of cell types, and Sertoli cell only. This sequence of progressive hypospermatogenesis was remarkably similar in both series. A separate category of maturation arrest was not recognized. Cell counts also correlated between right- and left-sided samples from the same patient in both series of biopsies. Reduction of tubular diameter, thickening of the tubular wall, and increase in Leydig cell density were often seen in severe stages of germ-cell impairment, although with an irregular distribution. PMID- 1516927 TI - Phagocytic capacity of human muscle fibers. AB - Isolated dead muscle cell fragments (apoptotic bodies [ABs]) were investigated by electron microscopy in different stages of phagocytosis. Phagocytosis of ABs was carried out by neighboring muscle cells. The mechanism of internalization took place in both mature and immature muscle cells and consisted of the progressive engulfment of ABs within cytoplasmic vacuoles and craters. In addition, concentrated microfilaments formed a dense ring in the muscle cytoplasm adjacent to the engulfed ABs. The above combination of membrane evagination and phagocytic vacuole formation as well as the extensive microfilament organization at the site of AB engulfment were analogous to the cytoplasmic response seen in the tissue of mononuclear phagocytic cells. PMID- 1516928 TI - Flow cytometric DNA analysis of vascular soft tissue tumors, including African endemic-type Kaposi's sarcoma. AB - Vascular tumors of the soft tissue display a wide spectrum of histologic features and biologic behavior. Flow cytometric DNA analysis was performed on 40 vascular tumors, including nine African endemic-type Kaposi's sarcomas, nine angiosarcomas, seven hemangiopericytomas, six glomus tumors, and nine capillary hemangiomas. Six of the nine angiosarcoma cases (67%) and one of the seven hemangiopericytomas cases (14%) were aneuploid. All benign vascular tumors and Kaposi's sarcomas were diploid. Clinically, five of the six angiosarcoma patients with aneuploidy died within 2 to 28 months, while the remaining patient, who had the smallest tumor (2 x 1 cm), survived more than 4 years after the initial diagnosis was made. All three angiosarcoma patients with diploidy died within 10 to 14 months. One hemangiopericytoma patient with aneuploidy died within 1 month. No cases of benign tumor recurred. These results suggest that most vascular tumors, which generally follow a benign clinical course, were diploid and that the majority of those with a poor outcome were aneuploid. However, flow cytometrically assessed DNA ploidy has no prognostic value in angiosarcomas or hemangiopericytomas. PMID- 1516929 TI - A thyroid biopsy with histologic features of both Riedel's thyroiditis and the fibrosing variant of Hashimoto's thyroiditis. AB - We describe a 36-year-old woman with clinical, laboratory, and histologic features of both Riedel's thyroiditis and the fibrosing variant of Hashimoto's thyroiditis. Features of the former included a hard, fixed thyroid mass and extensive involvement of perithyroidal tissues by dense fibrosis with lymphocytes, histiocytes, and plasma cells. Features supporting Hashimoto's thyroiditis included high serum titers of antimicrosomal and antithyroglobulin antibodies and the histologic findings within the thyroid gland itself: dense fibrous bands dividing the thyroid parenchyma into nodules composed of lymphoid follicles with germinal centers, plasma cells, and oxyphilic metaplasia of follicular epithelial cells. Although Riedel's thyroiditis and the fibrosing variant of Hashimoto's thyroiditis were once considered morphologic variants of the same disease, since the 1970s these diseases have been considered as distinct clinicopathologic entities. The coexistence of both diseases in a patient is rare and is probably coincidental in this instance. PMID- 1516930 TI - Renal insufficiency secondary to 2,8-dihydroxyadenine urolithiasis. AB - A 48-year-old man with a history of recurrent urolithiasis and chronic renal failure underwent a nephrectomy for a renal mass. At surgery the mass proved to be a calculus impacted in a dilated calyx. Gross examination of the kidney revealed chalky white deposits in the deep medulla and papillary tips. Histologic examination revealed chronic interstitial nephritis with brown spicules within some tubular epithelial cells and larger deposits of brown crystals within tubular lumina, the interstitium of the medulla, and papillary tips. Polarization microscopy revealed individual crystals scattered throughout the renal parenchyma. Although the arrangement of the crystals was reminiscent of uric acid, and, in fact, a clinical diagnosis of gouty nephropathy was made, x-ray diffraction analysis demonstrated crystals of 2,8-dihydroxyadenine. Enzymatic studies confirmed the complete absence of adenine phosphoribosyltransferase activity in erythrocyte lysates. PMID- 1516931 TI - Chondrosarcoma with intranuclear cytoplasmic vacuoles. PMID- 1516933 TI - Magnetic source images determined by a lead-field analysis: the unique minimum norm least-squares estimation. AB - The minimum norm least-squares approach based on lead field theory provides a unique inverse solution for a magnetic source image that is the best estimate in the least-squares sense. This has been applied to determine the source current distribution when the primary current is confined to a surface or set of surfaces. In model simulations of cortical activity of the human brain, the magnetic field pattern across the scalp is interpreted with prior knowledge of anatomy to yield a unique magnetic source image across a portion of cerebral cortex, without resort to an explicit source model. PMID- 1516932 TI - Chronic thyroiditis: thyroid function and histologic correlations in 601 cases. AB - Six hundred one patients with histologically proven "chronic thyroiditis" were assessed for the correlation of thyroid function to histologic findings. The histology of chronic thyroiditis was classified into four groups (oxyphilic, mixed, focal, and hyperplastic), and the thyroid function of patients was divided into hyperthyroid, euthyroid, latent hypothyroid, and overt hypothyroid, based on the laboratory data of serum triiodothyronine (T3), thyroxine (T4), and thyrotropin (TSH) levels, as well as thyrotropin-releasing hormone (TRH) tests. In the oxyphilic group (137 cases), 116 (85%) of the patients were classified as hypothyroid: 52 (38%) as latent hypothyroid and 64 (47%) as overt hypothyroid. In the mixed group (161 cases), the thyroid function of the patients varied. Thirty seven (23%) of the patients were classified as hyperthyroid, 61 (39%) as euthyroid, 54 (33%) as latent hypothyroid, and nine (5%) as overt hypothyroid. In this group thyroid function was intimately related to the ratio of replacement by hyperplastic-changed follicles and oxyphilic-changed follicles. In the focal group (149 cases), 123 (83%) of the patients were classified as euthyroid, while 22 (14%) were classified as latent hypothyroid. The frequency of latent hypothyroid patients increased in parallel with the severity of cell infiltration. In the hyperplastic group (154 cases), 130 (85%) of the patients were classified as hyperthyroid. In this series 19 patients under 10 years of age were included, and no difference in the distribution of histologic varieties was observed between juvenile and adult patients. Thyroid needle biopsy is a useful and safe tool, not only for the histologic diagnosis of chronic thyroiditis, but also for the evaluation of thyroid function and the identification of causes for hyperthyroidism or hypothyroidism. PMID- 1516934 TI - Assessing the effect of uncertainty in intracavitary electrode position on endocardial potential estimates. AB - The aim of this simulation study is to determine the effect of uncertainty in intracavitary probe electrode position on the accuracy of estimated endocardial potentials. Intracavitary probe position uncertainty is simulated by randomly moving an idealized probe surface about the center of an idealized left ventricular endocardial surface. These random deviations represent possible probe locations that are incorporated as correlated noise. An optimum inverse transfer coefficient matrix, relating intracavitary potentials to endocardial potentials, is computed and subsequently used to calculate the best linear estimate of the true endocardial potentials. For uncorrelated endocardial potentials and probe position uncertainty within 1.5 mm of the coordinates of the exact probe electrode locations, a root-mean-square (rms) error of 34.0% is obtained. Increasing probe position uncertainties to 3.0 and 6.0 mm results in rms errors of 60.8 and 88.3%, respectively. For endocardial potentials that are 90% dipolar, the rms errors for probe position uncertainties of 1.5, 3.0, and 6.0 mm are 11.3, 19.6, and 28.5%, respectively. These simulation results imply that position uncertainty of a multielectrode, intracavitary probe can be a major source of error in estimating endocardial potentials from intracavitary potentials. PMID- 1516935 TI - A minimum profile uniform current density electrode. AB - Present methods of determining the safe injected charge levels for disk-type electrodes are given in terms of an average charge density, although the charge density is higher near the periphery of the electrode. This paper describes an electrode that produces an injected charge density that is uniform over the surface of the electrode and thus permits maximum utilization of the surface. Charge density is the time integral of current density, and the alteration of the current density is obtained by adding curvature to the electrode and recessing it within a cylindrical insulating well. A novel numerical method is used to determine the recession and curvature, and this numerical method is also presented. The benefit of this technique is that it permits a reduction in the electrode size while maintaining the maximum safe injected charge level of a disk type electrode. A minimum profile uniform current density electrode and the algorithms used in its design are presented in this paper. Finally, a flat electrode that is recessed by as little as 1/10 of its diameter is shown to have an injected current density on the electrode surface that is superior to that of a flat surface mounted electrode. PMID- 1516936 TI - Neural stimulation with magnetic fields: analysis of induced electric fields. AB - Spatial distributions of the derivative of the electric field induced in a planar semi-infinite tissue model by various current-carrying coils and their utility in neural stimulation are evaluated. Analytical expressions are obtained for the electric field and its spatial derivatives produced by an infinitely short current element. Fields and their derivatives for an arbitrarily shaped coil are then obtained by numerical summation of contributions from all the elements forming the coil. The simplicity of the solution and a very short computation time make this method particularly attractive for gaining a physical insight into the spatial behavior of the stimulating parameter and for the optimization of coils. Such analysis is useful as the first step before undertaking a more complex numerical analysis of a model more closely representing the tissue geometry and heterogeneity. PMID- 1516937 TI - Maximal dynamic range electrotactile stimulation waveforms. AB - A new method to measure the dynamic range of electrotactile (electrocutaneous) stimulation uses both steepest ascent (gradient) and one-variable-at-a-time methods to determine the waveform variables that maximize the subjective magnitude (intensity) of the electrotactile percept at the maximal current without discomfort for balanced-biphasic pulse bursts presented at a 15-Hz rate. The magnitude at the maximal current without discomfort is maximized by the following waveform (range tested in parentheses): number of pulses/burst = 6 (1 20), pulse repetition rate within a burst = 350 Hz (200-1500), and phase width = 150 microseconds (40-350). The interphase interval (separation between positive and negative phases in a biphasic pulse) does not affect dynamic range from 0-500 microseconds. The number of pulses/burst has a large effect on the perceived dynamic range when this is measured using a subjective-magnitude-based algorithm, whereas it has little effect on the traditional dynamic range measure, i.e., (maximal current without discomfort)/(sensation threshold current). The perceived stimulus magnitude at the maximal current without discomfort is approximately twice as strong with 6 pulses/burst as it is with 1 pulse/burst (a frequently used waveform). PMID- 1516938 TI - A movement pattern generator model using artificial neural networks. AB - Artificial neural networks (ANN's) allow a new approach to biological modeling. The main applications of ANN's have been geared towards the modeling of the association and learning mechanisms of the brain; only a few researchers have explored them for motor control. The fact that ANN's are based on biological systems indicates their potential application for a biological act such as locomotion. Towards this goal, we have developed a "movement pattern generator," using an ANN for generating periodic movement trajectories. This model is based on the concept of "central pattern generators." Jordan's sequential network, which is capable of learning sequences of patterns, was modified and used to generate several bipedal trajectories (or gaits), coded in task space, at different frequencies. The network model successfully learned all of the trajectories presented to it. The model has many attractive properties such as limit cycle behavior, generalization of trajectories and frequencies, phase maintenance, and fault tolerance. The movement pattern generator model is potentially applicable for improved understanding of animal locomotion and for use in legged robots and rehabilitation medicine. PMID- 1516939 TI - Recognition of multiunit neural signals. AB - An essential step in studying nerve cell interaction during information processing is the extracellular microelectrode recording of the electrical activity of groups of adjacent cells. The recording usually contains the superposition of the spike trains produced by a number of neurons in the vicinity of the electrode. It is therefore necessary to correctly classify the signals generated by these different neurons. This paper considers this problem, and a new classification scheme is developed, which does not require human supervision. A learning stage is first applied on the beginning portion of the recording to estimate the typical spike shapes of the different neurons. As for the classification stage, a method is developed, which specifically considers the case when spikes overlap temporally. The method minimizes the probability of error, taking into account the statistical properties of the discharges of the neurons. The method is tested on a real recording as well as on synthetic data. PMID- 1516940 TI - Time-frequency transforms: a new approach to first heart sound frequency dynamics. AB - This study employed a new analytical tool, the Binomial joint time-frequency transform, to test the hypothesis that first heart sound frequency rises during the isovolumic contraction period. Cardiac vibrations were recorded from eight open chest dogs using an ultralight accelerometer cemented directly to the epicardium of the anterior left ventricle. The frequency response of the recording system was flat +/- 3 dB from 0.1 to 400 Hz. Three characteristic time frequency spectral patterns were evident in the animals investigated: 1) A frequency component that rose from approximately 40-140 Hz in a 30-50 ms interval immediately following the ECG R-wave. 2) A slowly varying or static frequency of 60-100 Hz beginning midway through the isovolumic contraction period. 3) Broad band peaks occurring at the time of the Ia and Ib high frequency components. The presence of rapid frequency dynamics limits the usefulness of stationary analysis techniques for the first heart sound. The Binomial transform provided much better resolution than the spectrograph or spectrogram, the two most common non stationary signal analysis techniques. By revealing the onset and dynamics of first heart sound frequencies, time-frequency transforms may allow mechanical assessment of individual cardiac structures. PMID- 1516941 TI - Analysis of ECG from pole-zero models. AB - A complete solution to the fundamental problem of ECG analysis, viz., delineation of the signal into its component waves, is proposed from a system theoretic point of view. The discrete cosine transform of a bell shaped biphasic function is approximated mathematically by a system function with two poles and two zeros, i.e., of order (2, 2). Using this concept as the basis, a pole-zero model of suitable order is derived from the discrete cosine transform (DCT) of the given signal using Steiglitz-McBride method. This model is expanded into a unique set of partial fractions each of order (2, 2), and a biphasic function is recovered from each one of these fractions in the inverse process. Each of the P and T waves usually requires only one biphasic function, while the QRS complex needs two or at most three such fractions. A one-to-one relationship between the pole pattern in the z-plane and component wave pattern in the time signal is established. Results of analysis of continuous strips of ECG show that the delineated component waves are in excellent agreement with the original waves both qualitatively and quantitatively. The method is robust for the analysis of signals with artifacts of various kinds, independent of the sampling rate used, and is free from ad hoc back and forth search procedures. PMID- 1516942 TI - Noninvasive optical polarimetric glucose sensing using a true phase measurement technique. AB - The focus of this paper was to describe the development and testing of a noninvasive true phase optical polarimetry sensing system to monitor in vivo glucose concentrations. To demonstrate the applicability of this optical sensor for glucose measurement, we first calibrated the system and then tested it in vitro using both a glass test cell filled with glucose solution in the physiologic range, with a path length of 0.9 cm to approximate one centimeter path length present in the anterior chamber of the eye, and then on an excised human eye. Our technique used helium neon laser light which was coupled through a rotating linear polarizer along with two stationary linear polarizers and two detectors to produce reference and signal outputs whose amplitudes varied sinusoidally with a frequency of twice the angular velocity of the rotating polarizer, and whose phase was proportional to the rotation of the linear polarization vector passing through the glucose solution. PMID- 1516943 TI - Measuring lung resistivity using electrical impedance tomography. AB - We propose the use of electrical impedance tomography (EIT) imaging techniques in the measurement of lung resistivity for detection and monitoring of apnea and edema. In EIT, we inject currents into a subject using multiple electrodes and measure boundary voltages to reconstruct a cross-sectional image of internal resistivity distribution. We found that a simplified, therefore fast, version of the impedance imaging method can be used for detection and monitoring of apnea and edema. We have showed the feasibility of this method through computer simulations and human experiments. We speculate that the EIT imaging technique will be more reliable than the current impedance apnea monitoring method, since we are monitoring the change of internal lung resistivity. However, more study is required to verify that this method performs better in the presence of motion artifact than the conventional two-electrode impedance apnea monitoring method. Future work should include experiments which carefully simulate different kinds of motion artifacts. PMID- 1516944 TI - Minimal repetition evoked potentials by modified adaptive line enhancement. AB - A new method called modified adaptive line enhancement (MALE) to obtain evoked potentials with minimum stimulus repetitions is described. The theory of MALE is developed and the assumptions made are tested and shown to be adequate in the case of brain-stem auditory evoked potential. The signal distortion are characterized and methods to alleviate the problem are developed. Using the weighted exact least squares lattice algorithm, the MALE method is implemented and applied to real data. It is shown that brainstem auditory evoked potential can be obtained with less than 40 repetitions using MALE method compared to 2000 required if conventional ensemble averaging method is used. PMID- 1516945 TI - Lewis K. Dahl Memorial Lecture. The renin system and four lines fo hypertension research. Nephron heterogeneity, the calcium connection, the prorenin vasodilator limb, and plasma renin and heart attack. AB - As the major regulator of arterial blood pressure and sodium balance, the renin axis supports normotension or hypertension via angiotensin-mediated vasoconstriction and angiotensin plus aldosterone-induced renal sodium retention. In this endocrine servo control, renal renin is released by hypotension or salt depletion; conversely, with hypertension or volume excess, plasma renin activity falls to zero. Accordingly, any renal renin secretion is abnormal in the face of arterial hypertension. Human hypertensive disorders comprise a spectrum of abnormal vasoconstriction-volume products (renin-sodium profiles). Excess plasma renin activity for the sodium balance is created by nephron heterogeneity in which a subpopulation of ischemic nephrons hypersecretes renin and retains sodium. This excess renin impairs adaptive natriuresis of neighboring normal nephrons. Research defining the pivotal role of vascular cytosolic calcium for transducing sodium or renin-mediated vasoconstriction explains the selective value of calcium antagonists for correcting the sodium-volume-mediated, and beta blockers or angiotensin converting enzyme inhibitors for correcting renin mediated, arteriolar vasoconstriction. The renin precursor prorenin appears to be physiologically active, causing selective vasodilation that offsets renin mediated vasoconstriction. Overactivity of prorenin may be involved in the hyperperfusion vascular injuries of diabetes mellitus and toxemias. Prorenin underactivity may facilitate renin-mediated ischemic vascular injury. In essential hypertension, undue plasma renin activity is powerfully and independently associated with heart attack risk. Conversely, patients with low renin activity are protected from heart attack despite higher blood pressures and greater age. Also, renin or angiotensin administration consistently causes vascular injury in the heart, brain, and kidneys of animals. These data suggest new potentials for the prevention of cardiovascular sequelae (heart attack and stroke) by using explicit strategies to curtail plasma renin activity. PMID- 1516946 TI - Adrenal and circulating renin-angiotensin system in stroke-prone hypertensive rats. AB - The plasma and adrenal renin-angiotensin system in stroke-prone spontaneously hypertensive rats (SHRSP) and Wistar-Kyoto (WKY) rats were examined in animals at 5, 11, 18, and 25 weeks of age. Plasma active renin was significantly increased in 18- and 25-week-old SHRSP with impaired renal function, whereas there was no difference in the plasma prorenin level or renal renin content between the two strains at all ages examined. Thus, the rate of activation of prorenin seems to be enhanced in the kidney of SHRSP with malignant hypertension. Adrenal renin contents were severalfold higher in SHRSP than WKY rats at all ages. However, adrenal angiotensin peptides were not increased in SHRSP aged 5 and 11 weeks. In 18-week-old SHRSP, adrenal angiotensin II (Ang II) and III (Ang III) levels were fourfold and 1.8-fold higher, respectively, than in WKY rats, accompanied by 1.5 fold higher plasma aldosterone. Increased adrenal angiotensin and plasma aldosterone were also found in 25-week-old SHRSP. Zonal distribution studies indicated that the elevated Ang II and III in SHRSP were derived mainly from the capsular tissue (the zona glomerulosa). To examine the contribution of circulating angiotensin to the adrenal angiotensin content, effects of bilateral nephrectomy on adrenal angiotensin and renin were examined in 18-week-old rats. At 24 hours after nephrectomy, plasma angiotensin, prorenin, and active renin were decreased to almost negligible concentrations. Conversely, in both adrenal capsular and decapsular tissues of SHRSP and WKY rats, neither angiotensin nor renin was significantly decreased after nephrectomy. These results suggest that the increase in adrenal capsular Ang II contents in SHRSP may be partly due to an enhanced local production of Ang II. PMID- 1516947 TI - Endothelin-1 augments pressor response to angiotensin II infusion in rats. AB - To assess possible roles of endothelin in the regulation of blood pressure, we studied effects of a subpressor dose of endothelin-1 (3 micrograms/kg/day) on chronic blood pressure responses to infusion of angiotensin II and norepinephrine in rats. Rats were infused with angiotensin II at a subpressor dose (400 micrograms/kg/day i.p.) or with norepinephrine at a subpressor dose (360 micrograms/kg/day i.p.) for 6 days. Systolic blood pressure was significantly elevated during combined infusion of endothelin-1 and angiotensin II, whereas endothelin-1 alone or angiotensin II alone failed to induce any significant changes in systolic blood pressure compared with vehicle alone. This effect was sustained for the whole experimental period and was not associated with any significant changes in body weight, fluid intake, urine volume, or urinary electrolyte excretion. In contrast, combined infusion of endothelin-1 and norepinephrine failed to elevate systolic blood pressure, and no significant difference in systolic blood pressure was observed for the whole experimental period among the four groups of rats with endothelin-1 in combination with norepinephrine, endothelin-1 alone, norepinephrine alone, and vehicle alone. The present results indicate that angiotensin II and endothelin-1, but not norepinephrine and endothelin-1, work synergistically to raise the blood pressure and also suggest the possibility that endothelin-1 may modulate blood pressure control. PMID- 1516948 TI - Chronic inhibition of nitric oxide synthesis. A new model of arterial hypertension. AB - Recent studies have indicated that acute inhibition of nitric oxide biosynthesis in the rat promotes arterial hypertension and renal vasoconstriction. We evaluated the renal and systemic effects of 4-6 weeks of nitric oxide blockade in Munich-Wistar rats receiving the nitric oxide inhibitor nitro-L-arginine orally. Age-matched untreated rats were used as controls. In an additional seven rats, nitric oxide blockade was carried out in conjunction with oral administration of the novel angiotensin II antagonist losartan potassium. Tail-cuff pressure rose progressively in nitro-L-arginine-treated rats, reaching 164 +/- 6 mm Hg at 4-6 weeks, compared with 108 +/- 3 mm Hg in controls. In rats concomitantly receiving losartan, tail-cuff pressure reached 125 +/- 6 mm Hg, still elevated compared with rats receiving losartan alone (98 +/- 3 mm Hg). Nitro-L-arginine-treated rats presented marked renal vasoconstriction and hypoperfusion, as well as a 30% fall in glomerular filtration rate and a 39% increase in filtration fraction. Treatment with Losartan normalized glomerular filtration rate, but not filtration fraction or renal vascular resistance. Plasma renin activity was elevated after nitro-L-arginine treatment. Renal histological examination revealed widespread arteriolar narrowing, focal arteriolar obliteration, and segmental fibrinoid necrosis in the glomeruli. In a separate group of rats, nitro-L-arginine administered for 1 week induced hypertension that was partially reversed by acute L-arginine, but not D-arginine or L-glycine, infusions. We conclude that chronic nitric oxide blockade may constitute a new model of severe arterial hypertension.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1516949 TI - Enhanced release of endothelium-derived relaxing factor in mineralocorticoid hypertension. AB - Ring segments of superior mesenteric arteries studied in vitro were used to determine the role of the vascular endothelium in regulating vascular contractile and relaxant sensitivity in deoxycorticosterone acetate (DOCA)-salt hypertension. Wistar rats were given DOCA (20 mg/kg s.c. twice per week) and 1% NaCl drinking water for 5 weeks. In ring segments containing endothelium, there was a decrease in contractile sensitivity to arginine vasopressin, no change in contractile sensitivity to norepinephrine and KCl, and no change in relaxant sensitivity to acetylcholine or isoproterenol in arteries from hypertensive rats compared with normotensive controls. Removal of the vascular endothelium by rubbing had no effect on the contractile response to arginine vasopressin and KCl or the relaxant response to isoproterenol in control arteries. In arteries without endothelium, DOCA-salt hypertension caused a threefold increase in contractile sensitivity for arginine vasopressin, norepinephrine, and KCl; a 50% reduction in maximal relaxation to isoproterenol; and a threefold decrease in relaxant sensitivity to sodium nitroprusside. Indomethacin (10 microM) had no effect on contraction or relaxation. However, N-monomethyl L-arginine unmasked altered contractile sensitivity to norepinephrine in arteries from DOCA-salt hypertensive rats. These data show that the endothelium compensates for increased contractile and reduced relaxant responses of vascular muscle in DOCA-salt hypertension by increasing the release of endothelium-derived relaxing factor. These data suggest that altered vascular responsiveness is masked by the endothelium, thus preventing these alterations from contributing to increased peripheral resistance during the development of DOCA-salt hypertension. PMID- 1516950 TI - Effect of home blood pressure and gender on estimates of the familial aggregation of blood pressure. The Tecumseh Blood Pressure Study. AB - Blood pressure (BP) readings from a single clinic visit are often used in population studies investigating the genetic basis of BP. We examined first degree relatives in the Tecumseh Blood Pressure study to compare heritability estimates of BP readings obtained in the clinic-office setting (the average of two seated readings) with self-reported home BP readings (the average of 14 readings) taken over a 1-week period. The hypothesis tested was that repeated BP readings obtained in the home over the 1-week period would have fewer artifacts (i.e., environmentally induced variability in BP) and thus would better estimate the true "basal" BP that, in turn, would improve heritability estimates. We and others assume that the true basal BP level is heritable. We therefore expected that this "true" BP, by reducing BP variability of offspring, would show a stronger between-sibling correlation and that it would correlate better to parental BP as measured in a clinic setting. Correlation coefficients were calculated between siblings in the present Tecumseh study using self-reported home BP and clinic BP readings. Among 380 siblings (average age, 31.4 years), correlation coefficients for the home readings were of the same magnitude as for office readings (home, r = 0.23, p less than 0.01; office, r = 0.24, p less than 0.01). When offspring clinic BP readings were compared with archived BP data on parents, the correlation between offspring clinic and parental clinic BP readings was stronger (r = 0.24, p less than 0.05) than the correlation of offspring home BP readings to parental clinic BP readings (r = 0.17, p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1516951 TI - Hematocrit, blood pressure, and hypertension. The Gubbio Population Study. AB - Baseline data from the Gubbio Population Study in north central Italy were used to investigate the relation of hematocrit to blood pressure and hypertension among 2,809 men and women aged 25-74 years. Independent of gender, age, and other confounders, the hypertensive group had a higher hematocrit than the nonhypertensive group (p less than 0.001). In comparison with the untreated hypertensive group, the hypertensive group being treated with diuretics or with other drugs only had similar mean hematocrit levels despite significantly lower blood pressures. Hematocrit was positively correlated with systolic pressure (r = 0.085, p less than 0.01 and r = 0.264, p less than 0.001 for men and women, respectively) and diastolic pressure (r = 0.214, p less than 0.001 and r = 0.266, p less than 0.001). In both sexes, whether or not the treated hypertensive group was included, age-adjusted prevalence of hypertension and average blood pressure were higher for persons in higher quintiles of hematocrit (p less than 0.001). The association of hematocrit with blood pressure and hypertension was significant and independent of several confounders. The regression coefficient of blood pressure on hematocrit ranged between 0.410 and 0.620 mm Hg per unit of hematocrit for systolic pressure and between 0.371 and 0.581 for diastolic pressure, depending on gender and whether the treated hypertensive group was included in multiple regression analysis. Based on exponentiation of the multiple logistic coefficient, prevalence of hypertension was at least two times greater for persons whose hematocrit levels were higher by 10 units. PMID- 1516952 TI - Ethnicity, pressor reactivity, and children's blood pressure. Five years of observations. AB - During the 5 years of this investigation, resting blood pressure and pressor reactivity were measured in 292 white children and 46 black children in 1987, 1988, 1989, and 1991. In 1987, all children were in the third grade; in 1991, the children were in the seventh grade. Reactivity was assessed with a standardized psychological stressor, a television video game. Children displayed significant stability of absolute blood pressure and heart rate reactivity between grades 3 and 7. At all examinations, black children demonstrated blood pressure reactivity that was significantly greater in magnitude (both absolute level and change from resting measurements) than that of white children. Black children exhibited significantly greater heart rate reactivity only when defined as change from the resting measurements; absolute levels of heart rate reactivity were comparable for blacks and whites. For black children, blood pressure reactivity in 1987 was the strongest predictor of resting blood pressure (both systolic and diastolic) in 1991. Among white children, resting blood pressure was the strongest predictor of future resting blood pressure. Further research is needed to determine if ethnic differences in children's pressor reactivity are associated with ethnic differences in the prevalence of hypertension. PMID- 1516953 TI - Brain atrophy in hypertension. A volumetric magnetic resonance imaging study. AB - To determine whether hypertension, the predominant risk factor for stroke and vascular dementia, is associated with brain atrophy, magnetic resonance imaging (MRI) scans were performed to quantify brain volumes and cerebrospinal fluid spaces. Eighteen otherwise healthy, cognitively normal older hypertensive men (mean +/- SD age, 69 +/- 8 years, duration of hypertension 10-35 years) and 17 age-matched healthy, normotensive male control subjects were studied in a cross sectional design. Axial proton-density image slices were analyzed using region-of interest and segmentation analyses. The hypertensive subjects had significantly larger mean volumes of the right and left lateral ventricles (p less than 0.05, both absolute volume and volume normalized to intracranial volume) and a significantly smaller normalized mean left hemisphere brain volume (p less than 0.05) with a trend toward significance for a smaller normalized mean right hemisphere volume (p less than 0.09). Four hypertensive subjects and one healthy control subject were found to have severe periventricular hyperintensities on T2 weighted MRI images. When data for these subjects were removed from the analyses, the normalized lateral ventricle volumes remained significantly larger in the hypertensive group. Lateral ventricle enlargement was not related to age or use of diuretics in the hypertensive group nor to duration of hypertension between 10 and 24 years. Our findings suggest that long-standing hypertension results in structural changes in the brain. Longitudinal studies will determine whether MRI associated changes are progressive and if such changes identify hypertensive subjects at increased risk for clinically apparent brain dysfunction. PMID- 1516954 TI - Resting and maximal forearm skin blood flows are reduced in hypertension. AB - To find whether the vasodilator capacity of nonacral skin is reduced in hypertension, we measured forearm blood flow by venous occlusion plethysmography in 10 seated normotensive (mean +/- SD mean arterial pressure, 94 +/- 5 mm Hg) and 10 hypertensive (112 +/- 9 mm Hg) men at rest for 39 minutes while the forearm was heated with water at 42 degrees C, a maneuver known to selectively and maximally vasodilate skin. Blood pressure, measured every 5 minutes, did not change with heating. We found that in the normotensive group resting forearm blood flow was higher (3.64 +/- 1.12 versus 2.48 +/- 0.58 ml/100 ml tissue per minute, p less than 0.001; normotensive group versus hypertensive group) and resting forearm vascular resistance lower (30.17 +/- 10.99 versus 48.88 +/- 17.37 mm Hg.min.100 ml tissue per minute, p less than 0.05; normotensive group versus hypertensive group), and maximal forearm blood flow with local heating was higher (29.32 +/- 11.99 versus 18.19 +/- 4.50 ml/100 tissue per minute, p less than 0.018; normotensive group versus hypertensive group and vascular resistance lower (4.07 +/- 1.04 versus 6.54 +/- 1.17 mm Hg.min.100 ml tissue per minute, p less than 0.005; normotensive group versus hypertensive group). To find whether this degree and duration of local warming maximally vasodilated the skin in hypertensive subjects (as it does in normotensive subjects), we measured forearm skin blood flow before and during local heating plus 10 minutes of ischemia using a laser Doppler flowmeter.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1516955 TI - Detection of glycyrrhetinic acid-like factors (GALFs) in human urine. AB - Patients with the syndrome of apparent mineralocorticoid excess and those who ingest licorice show markedly decreased 11 beta-hydroxysteroid dehydrogenase (11 beta-OHSD) and 5 beta-reductase activity; both are important for the deactivation of glucocorticoids and other steroid hormones. Glycyrrhetinic acid (GA), present as its glycoside in licorice, is a potent inhibitor of both 11 beta-OHSD and 5 beta-reductase and, as we have also shown, confers Na(+)-retaining properties on glucocorticoids and amplifies those of aldosterone and deoxycorticosterone. We report the results of our initial studies demonstrating the presence of naturally occurring substances, which inhibit both 5 beta-reductase and 11 beta-OHSD as does GA, in partially purified extracts of urine from normotensive men and nonpregnant and pregnant women. Since these substances exhibit GA-like activity, we have termed them GA-like factors (GALFs). This "inhibitory" material is heat stable and does not react with ninhydrin; the majority is not extractable with ethyl acetate and thus is not a "free" steroid. When further purified by high performance liquid chromatography with a methanol/water gradient, the majority of these GALFs appeared in two regions of inhibitory activity. The chemical nature of this material is currently being investigated. These experiments indicate that normal human urine contains GALFs that may play a role in Na+ homeostasis and regulation of blood pressure. PMID- 1516956 TI - Dietary sodium chloride increases blood pressure in obese Zucker rats. AB - In the rat, elevated arterial pressure is not consistently associated with obesity. The purpose of this study was to compare measurements of blood pressure, cardiac output, and total peripheral resistance in obese and lean Zucker rats on different NaCl intakes. Obese and lean rats drank either water or isotonic NaCl for 18 days. Tail systolic blood pressures of saline-drinking obese rats were higher than all other groups (p less than 0.05). NaCl intake did not affect blood pressure in lean rats, and blood pressures of water-drinking obese rats did not differ from those of lean controls. In a subsequent experiment, direct arterial pressures and cardiac outputs (thermodilution) were measured in separate groups of conscious rats that had been maintained on a 1% or 4% NaCl intake for 12 weeks. Arterial pressure was higher (p less than 0.01) in obese rats fed 4% NaCl (130 +/- 4 mm Hg) than in obese rats fed 1% NaCl (118 +/- 2 mm Hg) or than in lean rats fed either NaCl intake (118 +/- 3 mm Hg and 116 +/- 3 mm Hg, respectively). Cardiac output of obese rats was higher than that of lean rats (p less than 0.01); however, the NaCl-induced increase of blood pressure was accounted for by an increase of peripheral resistance (p less than 0.01). Thus, in contrast to the lean Zucker rat, arterial pressure of the obese Zucker rat is increased by a high dietary intake of NaCl. PMID- 1516957 TI - Drug metabolism by cytochromes P450 in the liver and small bowel. AB - Most drugs used clinically are metabolized by cytochromes P450. These enzymes have been best characterized in the liver, where it appears the major drug metabolizing P450s belong to three gene families. There appear to be remarkable differences among patients in the catalytic activity of each of the P450s within these three families, and it is increasingly evident that this heterogeneity accounts, at least in part, for differences among patients in response to many medications. In addition, it is clear that many important drug interactions result from induction or inhibition, or both, of the catalytic activity of P450s. Many interactions involving P450s can be reproduced in liver microsomes or in cultured hepatocytes, and it is likely that such studies will, in the future, alert physicians to potential drug interactions before they are reported. Finally, mounting evidence shows that many of the clinically relevant aspects of P450s that have been ascribed to the liver may in fact be occurring at the level of the intestinal mucosa. This finding has been demonstrated most clearly with CsA and P450IIIA, in which enterocyte metabolism appears largely to account for drug interactions and differences among patients in dosing requirements. It remains to be determined whether other enterocyte P450s are also clinically important. PMID- 1516958 TI - Gastrointestinal pharmacology. PMID- 1516959 TI - Prokinetic agents. AB - Prokinetic agents are medications that promote gastrointestinal motility. This article reflects the current state of our understanding of their mechanisms of action and their clinical utility in treating disorders of gastrointestinal motility, including gastroesophageal reflux, gastroparesis, small-intestinal dysmotility, and constipation. PMID- 1516960 TI - The role of newer antibiotics in gastroenterology. AB - The past decade has seen the introduction of a number of new potent antimicrobial agents, including broad-spectrum beta-lactam compounds such as the ureidopenicillins, third-generation cephalosporins, carbapenems, and monobactams; combinations of penicillins with inhibitors of beta-lactamase; and the quinolones. Most of these agents have excellent activity against enteric gram negative rods and some are active against anaerobic organisms, the two bacterial groups most likely to be encountered in gastrointestinal infections. Despite the potency and wide spectrum of many of these new agents, there are currently relatively few clinical situations in which any of the newer antimicrobials are the first-line agents for therapy or prophylaxis of gastrointestinal diseases. Reluctance to use these agents as first-line therapy is based on concerns about the selection and spread of resistant organisms, superinfection syndromes, and the high cost of many of the newer agents. Specific clinical settings in which these agents may be given preference are as follows: 1. use of a third-generation cephalosporin (cefotaxime or ceftriaxone) in the treatment of spontaneous bacterial peritonitis. 2. use of broad-spectrum beta-lactam compounds to provide gram-negative coverage in patients who should not receive aminoglycosides 3. use of a third-generation cephalosporin (ceftriaxone) in the treatment of central nervous system relapses of Whipple's disease 4. use of quinolones for the empiric treatment of suspected bacterial diarrhea in patients sufficiently ill to require empiric initiation of antibiotics. 5. use of quinolones for the treatment of chronic carriers of Salmonella typhi 6. use of norfloxacin for prophylaxis against SBP. As further experience with these new antimicrobial agents is obtained and as more bacteria develop resistance to current first-line agents, there can be little doubt that these new antibiotics will play an increasing role in the prevention and treatment of gastrointestinal disease. PMID- 1516962 TI - Immunosuppressants. AB - The role and pharmacology of a variety of immunosuppressant agents in the gastrointestinal tract and liver are reviewed in this article. Immunosuppressants covered include cyclosporine, corticosteroids, OKT3, antithymocyte globulin, azathioprine, methotrexate, and FK506. Guidelines for the use and complications of immunosuppressants in liver, pancreas, and small bowel transplantations are presented. Controlled and uncontrolled data for use of immunosuppressants in the management of gastrointestinal and hepatic disorders are also described. PMID- 1516961 TI - Prostaglandins, NSAIDs, and cytoprotection. AB - Although the effects of prostaglandins on gastrointestinal secretion, blood flow, and motility are quite well characterized, the mechanism underlying the cytoprotective actions of this group of lipid mediators has yet to be clearly established. It seems likely that the ability of NSAIDs to inhibit gastric prostaglandin synthesis is an important contributing factor to the pathogenesis of this disorder; however, it is still not clear why depletion of gastric prostaglandins predisposes the mucosa to injury. The study of prostaglandin receptors in the gastrointestinal tract is still in its infancy. As we learn more about the distribution of these receptors and develop specific agonists, it may become possible to develop prostaglandin analogues that are highly selective in enhancing mucosal defense but without the untoward effects frequently associated with analogues currently used clinically in the treatment of NSAID-induced gastropathy. PMID- 1516963 TI - Chemotherapy in the management of malignant gastrointestinal disease. AB - Malignancies arising from the gastrointestinal tract represent a diversity of histologies and natural history. The role of chemotherapy in the multidisciplinary approach to these malignancies is reviewed in this article. PMID- 1516964 TI - Gallstone-dissolving agents. AB - It can be anticipated that most new therapies will generate considerable excitement and optimism when introduced. This is usually tempered with time as additional clinical experience is gained and therapeutic limitations and adverse effects are realized. All areas in the nonsurgical management of gallstones have experienced this course--some, such as ESWL, rather meteorically. Perspective, however, is important and may allow the appropriate use of each of these modalities in the correct clinical setting. For example, ursodiol when given in sufficient dose to nonobese patients with small radiolucent stones, could be expected to effect partial or complete dissolution in as many as 75% of patients, with minimal or no adverse effects and in a cost-effective manner. Contact dissolution using MTBE has been shown to be safe and generally effective but requires diligent characterization of stones to avoid those that are pigmented or heavily calcified. Similarly, ESWL combined with oral bile acids may be consistently effective if treatment is restricted to patients with acceptable cholesterol stone burdens and if treatment can be safely continued until fragments are substantially reduced. Continued experience with each of these treatment options, along with advances in research providing new solvents and technologies or in preventing recurrence, is likely to establish this field in an appropriately optimistic light. PMID- 1516965 TI - Anesthesia equipment for infants and children. PMID- 1516966 TI - History and evolution of pediatric anesthesia equipment. PMID- 1516967 TI - Routine and special pediatric airway equipment. PMID- 1516968 TI - Respiratory gas monitoring in the pediatric patient. AB - Parents of soon-to-be-anesthetized children frequently express concern about their child's safety because they have heard that "anesthesia is the most dangerous part of the operation." Although I don't believe that statement was ever true, it is even less true today. With the development of reliable capnography and volatile agent measurement in infants and children, we have significantly reduced the risks associated with anesthesia. I think we can, and should, confidently reassure parents that the "anesthesia part of the operation" has been made much safer and that the child's breathing (as well as heart beat, temperature, oxygenation, etc.) will be vigilantly monitored by the anesthesiologist using both human senses and the latest in monitoring equipment. PMID- 1516969 TI - Monitoring neuromuscular function in the pediatric patient. PMID- 1516970 TI - Pediatric regional anesthesia equipment. PMID- 1516971 TI - Anesthesia laboratory for the pediatric operating room. PMID- 1516972 TI - Intravenous infusion equipment. PMID- 1516973 TI - Pediatric breathing circuits and anesthesia machines. PMID- 1516974 TI - Temperature monitoring in pediatric anesthesia. AB - Thermoregulatory responses in infants and children are now fairly well understood. The phenomenon of heat loss in children during surgery is widely acknowledged. Hypothermia is most likely to occur during long surgical procedures in an air-conditioned operating room, particularly when respiration is controlled. Its consequences have prompted clinicians to take extra care in maintaining normothermia, especially in the very young. It is well known that anesthetized infants and children are capable of active thermoregulation and that their vasoconstrictive threshold differs little from that in adults [31]. Body temperatures can be measured using a variety of thermometers. Most clinically used thermometers are reasonably accurate. Perioperative hypothermia results from decreased metabolic heat production, increased environmental heat loss, redistribution of heat within the body, and anesthesia-induced inhibition of thermoregulation. Radiation and convection from the skin surface combine with evaporation from tissues inside surgical incisions to decrease mean body temperature. Perioperative hypothermia can be limited by prewarming the skin surface before induction of anesthesia, warming the operating room, humidifying the airway, and warming intravenous fluids. PMID- 1516975 TI - Noninvasive monitoring in the pediatric patient. AB - Substantial technological improvements have been made in the field of noninvasive monitoring. Additionally, our understanding of what these monitors will and will not do has changed the practice of pediatric anesthesia. In the 1990s it has become apparent that many cardiorespiratory parameters can be easily and safely monitored noninvasively. It is also apparent that no single monitor is capable of providing all the information necessary to provide safe anesthetic care. Those of us who provide anesthesia for children on a regular basis have come to appreciate these monitors not as an annoyance required for medicolegal protection but as tools that help improve the quality and safety of the anesthesia care our children receive. Use of these monitors represents the leading edge of an effort to reduce anesthesia morbidity and mortality to zero. PMID- 1516976 TI - Invasive monitoring in the pediatric patient. PMID- 1516977 TI - Testicular microcirculation--a forgotten essential in andrology? PMID- 1516978 TI - Effect of different culture techniques used to induce capacitation on the chromatin stability of human sperm. AB - To validate an in-vitro bioassay for assessing chromatin stability of human sperm, 38 semen samples from infertile men were studied using sodium dodecyl sulphate, an anionic detergent which disorganizes only the cytoplasmic membrane. Assay sensitivity was 50 sperm, whilst the within- and between-assay variation, and the between-observer variation were found to be within the accepted range for this type of bioassay. The influence of different in-vitro treatments currently used in some clinical assisted fertilization programmes was evaluated: a destabilizing effect occurred in Grade I (stable) and Grade III (swollen) sperm. In the former, all treatments reduced stable sperm; in the latter, a significant (P less than 0.001) increase in swollen sperm was shown with two methods that used Ham's F-10 as culture medium. Different chromatin patterns found in the treated sperm suggest the possibility that the recovered samples could be modified compared to their status at the time of isolation. PMID- 1516979 TI - A double-blind trial of clomiphene citrate for the treatment of idiopathic male infertility. World Health Organization. AB - A multicentre, randomized double-blind study was performed to assess the effect on male fertility of treatment with low dose clomiphene citrate. One hundred and ninety couples were included in whom the male diagnosis was idiopathic impairment of semen quality, and the female partner had no demonstrable abnormality or was under successful treatment for a minor endocrine problem. A total of 1308 couple months were studied. Men received either 25 mg clomiphene citrate daily or placebo for 6 months. The cumulative life-table pregnancy rates at 8 months were 11.7% and 8.1% in the placebo and clomiphene groups respectively. There were no significant differences between the changes in semen quality during intake of either clomiphene or placebo. This study provides no evidence for the efficacy of clomiphene citrate for the treatment of idiopathic male infertility. PMID- 1516980 TI - Deficiency in major high molecular-weight seminal proteins in men producing poorly coagulating and alkaline liquid ejaculates. AB - Using SDS-PAGE three major high molecular-weight coagulum proteins (57, 75 and 79 kD) were identified in unliquefied human ejaculates. Washed coagulum was prepared at pH 4.5 and demonstrated negligible proteolysis as determined by a highly sensitive fluorescamine-based method. Laser densitometric scanning of these high molecular-weight proteins in unliquefied ejaculates in relation to their coagulational failure revealed that the total content of 57, 75 and 79 kD proteins in whole semen represented approximately 44% of levels in the normally coagulated, approximately 24% in poorly coagulated (P less than 0.005) and approximately 3% in the non-coagulated (alkaline liquid, P less than 0.001) samples. The findings imply that these predominant high molecular-weight proteins play a major role in human seminal coagulum formation. PMID- 1516981 TI - Therapy with human chorionic gonadotrophin alone induces spermatogenesis in men with isolated hypogonadotrophic hypogonadism--long-term follow-up. AB - The effects of long-term (14-120 months) hCG-treatment of 17 male patients affected by isolated hypogonadotrophic hypogonadism (IHH) on testicular volume, plasma testosterone levels, and sperm concentration were assessed. Mean testicular volume increased from 3.8 +/- 0.2 (Mean +/- SEM) ml to a maximal of 14.9 +/- 1.1 ml after 22.2 +/- 2.3 months of hCG treatment. Maximal testicular volume correlated positively with the volume recorded before the patients had undergone any previous treatment. Testicular growth was also analysed by sorting the patients into two sub-groups according to whether their initial testicular volume was less than 4 ml (small testis subset, STS) or greater than or equal to 4 ml (large testis subset, LTS), supposedly indicating complete or partial gonadotrophin deficiency, respectively. Testicular volumes in the LTS group were always greater than those of the STS. Plasma testosterone levels reached adulthood values during hCG treatment and no statistically significant difference was detected between LTS and STS patients with IHH. Thirteen patients (70%) became sperm-positive during treatment with hCG alone; five out of eight (60%) were STS patients and eight out of nine (90%) were LTS. In addition, LTS patients always had a greater sperm output than did STS patients. Sperm concentration correlated positively with maximal testicular volume, but not with patient age, length of treatment, or initial testicular volume. The administration of hMG to eight of these patients caused an increase in testicular volume in two patients but the mean volume was not statistically different from that recorded at the end of treatment with hCG alone. Similarly, sperm concentration improved in three patients but again it did not differ significantly from that achieved in the course of hCG treatment. It is noteworthy that one patient became sperm-positive after the addition of hMG to his therapeutic regimen. Among sperm-positive patients attempting conception, seven out of 10 succeeded, two of whom were from the STS group. In summary, this study indicates that hCG alone is an effective treatment to induce complete spermiogenesis in IHH patients regardless of their initial testicular volume. However, a number of IHH patients may benefit from the addition of hMG in terms of testicular volume, sperm output, and pregnancy outcome. PMID- 1516982 TI - Sperm nuclear instability and staining with aniline blue: abnormal persistence of histones in spermatozoa in infertile men. AB - During mammalian spermiogenesis, replacement of the somatic histones by basic proteins, the protamines, allows normal sperm nuclear condensation. In this study we have evaluated the degree of chromatin compaction in spermatozoa from 191 infertile subjects, affected by different testicular disorders, compare with that in 50 fertile sperm donors (controls). In infertile men, there was a higher percentage of unstable spermatozoa after incubation with sodium dodecyl sulphate (SDS) and of stained spermatozoa after staining with aniline blue (P less than 0.001 vs. controls). Furthermore, a positive linear correlation was found between SDS-unstable spermatozoa and stained spermatozoa (P less than 0.001), suggesting that sperm instability was related to a defect in histone-replacement by sperm specific nucleoproteins, protamines. When the patients were considered according to pathology, high sperm nuclear instability and a high percentage of stained spermatozoa were detected in groups affected by varicocele, idiopathic infertility and in patients with a history of unilateral cryptorchidism. In the latter group the same alterations were observed even when the cryptorchid testis had been removed during surgery. In the group with a past history of mumps orchitis these parameters did not show any difference when compared with controls. PMID- 1516983 TI - Efficacy of varicocele embolization versus ligation of the left internal spermatic vein for improvement of sperm quality. AB - Efficacy of surgical varicocelectomy versus embolization of the spermatic vein was studied in 137 men diagnosed as suffering from left varicocele. The men were divided randomly into three groups according to the methods of treatment: A- embolization of the internal spermatic vein (51 men); B--Ivanissevich technique of high ligation of the spermatic veins (43 men); and C--Bernardi technique of high ligation (43 men). The groups were similar in terms of age, duration of infertility and possessed semen characterized as oligoteratoasthenozoospermia. The fertility of the female partners was evaluated carefully and they were found to be potentially fertile. Varicocele was diagnosed by at least two of the following methods: physical palpation during valsalva manoeuvre, venography, or scrotal scanning using the technetium pertechnetate radioactive method. Semen quality was assessed before treatment and at 3, 6 and 9 months post-treatment. Fecundity was followed-up for 18 months. The major results were: (i) Shrinkage of the varicocele was found in all three groups studied. The same rate of recurrence was recorded in the three groups (24%, 37% and 35% in groups A, B and C, respectively). (ii) Improvement of sperm quality was significant in groups A and B, with better results in group B. (iii) The pregnancy rate was significantly higher in group B, compared with A (38.2% vs. 20.6%; P less than 0.05). Thus, high ligation of the internal spermatic vein yields better results than low ligation or embolization as far as semen quality and pregnancy is concerned. PMID- 1516984 TI - Temporal changes in the serum levels of gonadotrophins and testosterone in male rats bearing subcutaneous implants of 5 alpha-dihydrotestosterone. AB - This study has assessed the effect of s.c. implants of 5 alpha dihydrotestosterone (DHT) on the blood levels of testosterone and gonadotrophins in intact and castrated adult male rats. The rats were bled via cardiac puncture at 1, 3, 7, 14, 21, 28, 35, 42, 49, 56, 63 and 70 days after DHT implantation. On days 28 and 49 post-implantation, rats were injected with LHRH (25 ng) and bled 15 min later. In intact rats bearing DHT implants, the serum levels of LH and testosterone were suppressed significantly with no significant changes in FSH levels. Ventral prostate, seminal vesicles and the pituitary were reduced significantly in weight when compared with controls with empty implants. DHT significantly inhibited LHRH-induced release of FSH in intact rats. In castrated rats, DHT implants inhibited the secretion of both LH and FSH, with a rise in serum DHT levels. DHT stimulated the LHRH-induced release of LH but inhibited FSH. DHT implants increased the weight of the seminal vesicles and ventral prostate but inhibited the weight of the pituitary when compared to castrated rats bearing empty implants. This study demonstrates specific inhibition of serum LH and testosterone by DHT implants in intact adult rats. PMID- 1516985 TI - Does follicle-stimulating hormone or pregnant mare serum gonadotrophin influence testicular blood flow in rats? AB - Treatment of adult rats with 25 iu follicle-stimulating hormone (FSH) did not influence testicular blood flow, serum testosterone, vasomotion or intravascular leucocyte concentration at 6, 12 and 24 h after treatment. Treatment of adult rats with 50 iu pregnant mare serum gonadotrophin (PMSG) resulted in a two-fold increase in testicular blood flow at 24 h, and an increase in interstitial fluid volume at 36 h after treatment. This PMSG-induced increase in blood flow did not occur in Leydig cell-depleted animals, suggesting that the effect on blood flow is mediated via the Leydig cells. PMSG injection stimulated testosterone secretion but it did not influence vasomotion, and it only marginally increased the secretion of leucotactic factors in the testis. The present study suggests that FSH has no apparent effects on testicular blood flow and that the effects of PMSG (a hormone with both FSH and LH-like activity) is mediated via stimulation of the Leydig cells. PMID- 1516986 TI - Non-occlusive mesenteric infarction (NOMI) in dialysis patients--risk factors, diagnosis, intervention and outcome. PMID- 1516987 TI - Hypoglycemia in diabetics on dialysis with poor glycemic control: hemodialysis versus continuous ambulatory peritoneal dialysis. AB - Eight diabetic men with poor glycemic control, probably worsened by severe congestive heart failure and gastroparesis, were sequentially dialyzed by CAPD and hemodialysis. Mean blood glucose concentration, blood glycosylated hemoglobin, and insulin dose were higher during CAPD than during hemodialysis. Among blood glucose determinations, however, the frequency of hypoglycemia (glucose less than 3.3 mmol/L) was higher during hemodialysis (13.2 +/- 8.9%) than during CAPD (2.8 +/- 2.1% p = 0.012), whereas the frequencies of hyperglycemia (glucose greater than 11.1 mmol/L) and euglycemia (glucose between 3.5 and 11.1 mmol/l) did not differ between the two dialysis modalities. Furthermore, hypoglycemia was severe during hemodialysis and was associated with two deaths. There were no deaths linked to abnormalities in blood glucose concentration during CAPD. When hypoglycemia is frequent in diabetics with poor glycemic control, CAPD is preferable to hemodialysis. PMID- 1516988 TI - Blood pressure after three different forms of correction of anemia in hemodialysis. AB - It is not known whether recombinant human erythropoietin has a direct, clinically apparent pressor effect in hemodialysis patients or whether hypertension developing or aggravated in these patients merely reflects increased hematocrit. We compared blood pressure after three different methods of partial correction of anemia in hemodialysis patients with similar baseline hematocrits (erythropoietin n = 12, intravenous iron alone n = 10, androgens n = 9). Shortly after the start of treatment and with a minimally increased hematocrit, the need for antihypertensive medication increased in the erythropoietin group. No such pressor effect was observed with iron or androgens. These data suggest a direct hypertensive effect of erythropoietin in some patients on hemodialysis. PMID- 1516989 TI - Can teledialysis help in the clinical management of patients on remote hemodialysis? AB - This study investigated whether transmission of the parameters monitored from a remote center to the main center could improve the control of a dialysis session. The parameters of the computer connection module Monitral SC in remote and main centers, were transmitted by means of the Hospal data collection software (Demoplus) by modem, to the host computer. Each remote center can be temporarily disconnected, if necessary, from the telephone line and linked directly to a local computer. We checked 101 hemodialyses. The dialysis was monitored from filter washing to disconnection of the patients and the following parameters were selected: backfiltration during washing and hemodialysis: ultrafiltration, conductivity and temperature. From the sessions recorded (93%) we observed that backfiltration during the filter preparation phase was high (30%) in 28 sessions. Backfiltration during the preparatory phase is the major problem for correct management of dialysis sessions. The high percentage in which ultrafiltration had to be stopped shows that control of this parameter is still not ideal. Finally, the collection of monitor parameters and the comparative analysis of clinical data is useful for improving dialytic management. PMID- 1516990 TI - Beta 2-microglobulin synthesis of mononuclear cells in chronic dialysis patients. AB - Beta 2 microglobulin (B2M) has been identified as a major component of amyloid deposits. This study was designed to determine whether changes occur in the synthesis of B2M in dialysis patients. Mononuclear cells (MNC) were isolated in peripheral blood from healthy volunteers, patients on hemodialysis (HD) and on continuous ambulatory peritoneal dialysis (CAPD). MNC were cultured in a medium of RPMI 1640 with or without interleukins IL-1, IL-2 or interferon INF-r. B2M in the cultured cells and supernatant was measured by enzyme immunoassay. IL-2 or INF-r stimulated B2M synthesis was significantly lower (25%) in patients on HD than in normal controls regardless of the type of dialysis membranes used, with no change in basal B2M synthesis. No differences were detected between healthy volunteers and CAPD patients. Preincubation of MNC with complement--activating or non-complement--activating membrane had no influence on B2M synthesis. The basal B2M synthesis of MNC significantly increased after a 4-hour HD regardless of the membranes used, and IL-2 and IFN-r stimulated synthesis were both essentially the same before and after HD. It was thus concluded that maximum capacity for B2M synthesis of MNC decreases in hemodialysis patients. This low responsiveness of MNC may be partially the cause for the reduction in cell-mediated immune response in HD patients. PMID- 1516991 TI - In vivo clearance and elimination of nine marker substances during hemofiltration with different membranes. AB - The handling of low, middle and high molecular weight markers was examined in seven stable dialysis patients during hemofiltration with different membranes. Four membranes were examined in a randomized, crossover order (polysulfone, polyamide, AN69 polyacrylonitrile, Asahi polyacrylonitrile) by measuring plasma and dialysate concentrations of phosphate, creatinine, vitamin B12, beta 2 microglobulin, furanic acid, hippuric acid, retinol-binding protein, alpha-1 antitrypsin, and albumin. Sieving coefficients and plasma clearances of beta 2 microglobulin or retinol-binding protein were markedly or slightly lower during hemofiltration with the Asahi polyacrylonitrile membrane than with the other membranes (highest removal with polysulfone/AN69 polyacrylonitrile membranes). No differences of obvious clinical relevance could be seen between the four membranes. A high beta 2-microglobulin removal rate might be important to prevent dialysis-associated amyloidosis. PMID- 1516992 TI - Acute renal failure in hepatitis A. AB - A 21-year-old man developed acute renal failure early in the course of hepatitis A infection and recovered after 17 days. There was no evidence of pre-renal azotemia, the hepato-renal syndrome, ischemic acute tubular necrosis, rhabdomyolysis, or thrombotic microangiopathy. There was, however, transient proteinuria and hypocomplementemia. It would appear that the renal failure resulted from viral-induced injury, either direct or mediated by immune complexes. PMID- 1516993 TI - A modular mock circulation for hydromechanical studies on valves, stenoses, vascular grafts and cardiac assist devices. AB - P6vices for hydrodynamic simulation are required in a variety of studies such as device evaluation, cardiovascular modeling and for student training. Most studies today use different, incompatible circuits, which must be redesigned for every new application. To obtain a universal apparatus, a unitized system with standard connectors was developed. Three types of connectors were selected: 1" flange connectors, 1/2" tubing connectors and Luer-connectors with a 2 mm lumen. The complete system consists of reservoirs, throttles, valve holders, adapters for Doppler ultrasound probes, and converters to link these basic diameters. The apparatus can be driven by membrane, centrifugal and geared pumps. The system has successfully been used in echocardiographic studies of stenosis and valvular insufficiency, for pulse propagation in vascular grafts, and to test the hydraulic performance of cardiac assist devices. Flow rates between 0.1 and 30 l/min and pressure gradients up to 250 mmHg were achieved. In practical use, the system can be adapted to suit various investigations, with minimal expense. Standardization of the parts and connectors results in simple documentation and good reproducibility. PMID- 1516994 TI - Lung involvement in systemic sclerosis sine scleroderma treated by plasma exchange. AB - Systemic sclerosis sine scleroderma can present in some patients as pulmonary interstitial fibrosis. Until now ten cases with this particular clinical variant, all men, have been reported in the literature. The knowledge of systemic sclerosis sine scleroderma presenting as lung interstitial involvement is important in clinical practice for an early diagnosis and correct therapeutic strategy. This work reports the clinico-serological features of two further cases, one a woman, of systemic sclerosis sine scleroderma with prevalent lung involvement, and describes the effects of therapeutic plasma exchange. PMID- 1516995 TI - Spontaneous dialytic ultrafiltration with intraperitoneal reinfusion of the concentrate versus large paracentesis in cirrhotic patients with intractable ascites: a randomized study. AB - Dialytic ultrafiltration of ascites through a hemofilter associated with peritoneal reinfusion (DUF) of the concentrate has been proposed for the treatment of refractory ascites. In five cirrhotic patients, 18 ascites evacuation procedures were randomized either to DUF (n = 8) or to large paracenteses (LP) (n = 10). The effects of these two methods on hemodynamic and renal function were assessed. After DUF, the protein concentration in ascites increased transiently from 28 +/- 7 g/l to 64.8 +/- 8 g/l (p less than 0.04); urinary output increased from day 1 to day 4 (1000 +/- 100) VS 1430 +/- 140 ml/24h; p less than 0.02). After LP, ascitic protein concentration and urinary output were unchanged. No side effects were observed with the two methods. The mean amount of albumin infused was 20 +/- 15 g after DUF and 15 +/- 5 after LP (ns). PMID- 1516996 TI - Stapedius reflex in patients with an inner ear prosthesis. AB - The stapedius reflex elicited by electrical stimulation was investigated in 21 deaf individuals supplied with an inner ear prosthesis. All patients were implanted with the Vienna cochlear implant using intra or extracochlear electrodes. Analog stimulation with sinus bursts of various durations (25, 50, 100, 300, 500 ms) and frequencies (125, 500, 1000, 2000 Hz) was used. The time course of the contralateral acoustic reflex was monitored using a fast-response impedance meter. The stapedius reflex was observed in about half of the cases. Reflex threshold was observed at a stimulation level close to uncomfortable loudness. The time course in case of electrical stimulation differs in some aspects (rise time, onset) from acoustic stimulation in hearing individuals. Temporal integration of the stapedius reflex was observed also in case of electrostimulation through the cochlear implant. PMID- 1516997 TI - Sexual function with and without erythropoietin therapy. PMID- 1516998 TI - Correction of pancytopenia and hemochromatosis by r-huEPO in a hemodialysis patient. PMID- 1516999 TI - Maximum likelihood estimation of signal detection model parameters for the assessment of two-stage diagnostic strategies. AB - The methodology of Receiver Operating Characteristic curves based on the signal detection model is extended to evaluate the accuracy of two-stage diagnostic strategies. A computer program is developed for the maximum likelihood estimation of parameters that characterize the sensitivity and specificity of two-stage classifiers according to this extended methodology. Its use is briefly illustrated with data collected in a two-stage screening for auditory defects. PMID- 1517000 TI - Mathematical modeling of the human fetal arterial blood circulation. AB - A mathematical model of the human fetal arterial circulation based on mass and momentum conservation for one-dimensional flow is presented. We simplified the fetal arterial vascular system from the heart to the placenta, defined 16 anatomical segments and studied the characteristics of the vascular system in relation to changes in morphology and hemodynamics. The two-step Lax-Wendroff finite difference scheme was used to solve the system of equations, after introducing the rheological constants, the diameter and length of the segments measured by two-dimensional imaging and the mean arterial velocity at the inlet segments obtained by pulsed Doppler. The model was validated by comparing the numerical results to our non-invasive ultrasound direct measurements and to previous published data. PMID- 1517001 TI - GALE: a graphics assisted learning environment for computer-based interactive videodisc education. AB - GALE, a Graphics Assisted Learning Environment, is a computer-based interactive videodisc authoring tool. GALE was created as the authoring package for AI/LEARN/Rheumatology, an independent study system for teaching rheumatology to medical trainees. GALE has potential widespread application beyond rheumatology. Interactive videodisc technology is a prime feature of GALE. Other highlights are: WordPerfect macros which simplify programming, graphics-based large text characters, tracking of user responses, hypertext-like definition capabilities, color coded screens to distinguish between hypertext branches and the mainstream of the course content and ability to overlay text on the video image. GALE runs on a PC-compatible computer with selected Pioneer LaserDisc players. GALE uses WordPerfect 5.1 for text editing and has been designed for use by non programmers. PMID- 1517002 TI - Simulation modelling for HIV infection and AIDS. AB - In this paper we describe a computer model developed jointly by mathematicians and medical consultants. The aim of the model is to provide practical help to people involved with caring for HIV-infected patients. The program is easy to use and can provide a wide variety of output, ranging from resource requirements and costs to detailed clinical information. The model uses the technique of computer simulation to study the progression of HIV-related diseases in a set of patients. The model can help planners concerned with the broad issues of health care provision, as well as clinical users whose main interest is the management and treatment of individual patients. The model is currently being tested in the Department of Genito-Urinary Medicine in the Royal Victoria Hospital, Bournemouth. The potential capability of the model is illustrated by some results from program runs using data from a set of Bournemouth patients. We argue that the power and flexibility of computer simulation as a technique for dealing with uncertainty and variability is especially appropriate in the case of HIV and AIDS. PMID- 1517003 TI - Basophil degranulation control. AB - We first present a global simulation model describing inhibition of human basophil degranulation by means of high dilutions. Then we study an optimal control problem associated to a non-linear compartmental model. This control is associated to an antigen concentration. For solving this control problem we used a dynamic programming method. PMID- 1517004 TI - Relationship among age, serum cholesterol level and population percentile in adults. AB - The data of the National Health and Nutrition Examination Survey comprehensively have shown that distributions of serum cholesterol levels in the US adult population are age and sex dependent. General formulas were constructed and published by the author on the basis of the data of the National Health and Nutrition Examination Survey to predict the population percentile for serum cholesterol levels by age. A mathematical model and a computer program previously published by the author were employed in the study. Analysis of the computer assisted predicted and the National Health and Nutrition Examination Survey reported percentiles indicated that the designed program for calculating the formulas was accurate and reliable. The formula could determine the relationship among adult age, serum cholesterol level and population percentile. A comprehensive table and nomograms that show the relationship among age, serum cholesterol level and population percentile in men and women for each year group between 20 and 79 years of age are obtained in this study, using the previously published formulas. The population percentiles predicted by the formula may reflect the relative degrees of risk for coronary heart disease. The population percentile, simultaneously expressed as 'risk percentile', may be used as a parameter of risk assessment for coronary heart disease for all adult ages and sexes. Seventy-five population percentile of serum cholesterol level is suggested as a cutoff point of high 'risk percentile' for coronary heart disease. This information on the percentile may have a preventive diagnostic value for detection, evaluation and treatment of patients with high cholesterol levels. The comprehensive table and nomograms showing the relationship among age, serum cholesterol level and population percentile may be hopefully available to clinicians and useful in their medical practice and may also be helpful in future clinical investigation. PMID- 1517005 TI - Difficulties with studying accelerated aging. PMID- 1517006 TI - A four-parameter generalization of the Gompertz curve suitable for somatic growth. AB - A four-parameter generalization of the Gompertz curve is proposed which passes through the origin with respect to total age and is often more suitable for somatic growth than the three-parameter Gompertz curve. Applied to published cross-sectional data on 44 male white rats, the new curve differs from another four-parameter curve proposed earlier by Jolicoeur and Pirlot (1988) in that it does not involve initial growth delays and it avoids an arbitrary assumption concerning the initial curvature, but it nevertheless yields approximately similar descriptions of chronological growth and complex allometry. The new four parameter version of the Gompertz curve may be useful in cases where other growth curves do not provide a satisfactory fit. PMID- 1517007 TI - Growth and utilization of nutrients in newly-hatched chick with or without removal of residual yolk. AB - Two experiments were conducted to characterize the growth and utilization of nutrients in newly-hatched chicks, and to determine nutritional roles of residual yolk by comparing chicks with or without deutectomy (removal of residual yolk sac). Rapid growth during 14 days after hatch was shown in the fed chicks. Daily feed intake increased linearly for 15 days posthatch, resulting in a high efficiency (80%) of feed utilization. Residual yolk in the abdomen averaged 6.4 g at hatch and rapidly disappeared during the first 3 days. Posthatch starvation resulted in a decrease in carcass lipid content but did not modify the disappearance rate of yolk in the abdomen. Weight of the digestive tract per unit body weight increased markedly up to 3-7 days of age followed by a gradual decrease in the fed chicks. Metabolizability of dietary energy and absorption of dietary lipid were the highest at hatch, then declined to the lowest at day 5 or 6, and thereafter gradually increased. The deutectomy did not influence the metabolizability of dietary energy and lipid, and the carcass composition, but delayed the growth by 2 days behind the control chicks. These results indicate that the metabolism and nutrition of newly-hatched chicks markedly fluctuate and that the residual yolk has crucial roles in complementing the nutrients absorbed to assure their rapid growth posthatch. PMID- 1517008 TI - Morphometrical analysis of the short-term effects of hypophysectomy and food restriction on skeletal muscle fibers in relation to growth and aging changes in the rat. AB - Muscle fiber growth is impaired by lack of hormonal influence. In the case of the gastrocnemius muscle of the male Wistar rat, ablation of the pituitary at age 60 days results in cessation of the growth of type 1 muscle fibers, and a reduction in the size of type 2 muscle fibers at 120 days of age, 60 days after hypophysectomy. The effects of food restriction, which are known to reduce pituitary hormone secretion, are not as great as hypophysectomy in inhibiting muscle fiber growth. Food restriction slowed the growth of type 1 muscle fibers (hypophysectomy abolished growth) and caused cessation of growth of type 2 muscle fibers (hypophysectomy caused atrophy). PMID- 1517009 TI - Bibliography: growth and embryonic development and aging. PMID- 1517010 TI - NMR study on solution structure of the site-specific mutant Leu48----Ala transforming growth factor alpha. AB - The NMR spectra of the Leu48----Ala mutant of human transforming growth factor alpha were compared to that of the wild-type. All chemical shift changes are less than or equal to 0.02 ppm with the exception of resonances associated with residues 47, 48 and 50 (all less than or equal to 0.07 ppm). Minimal changes were observed for NOEs associated with residues Val1 to His45. The weakening of some NOEs associated with the region Ala46-Ala50 may suggest a slightly increased flexibility for this region. Refinement of the previously calculated wild-type structures using distance constraints derived from the L48A mutant had little overall effect. Leu48-Ala50 is ill-defined for both wild-type and mutant proteins. These results suggest that Leu48 has no structural role and thus must be an important factor in the protein-receptor interface. PMID- 1517011 TI - 1H-NMR conformational study of a synthetic peptide derived from the consensus sequence of annexins. AB - The solution conformation of a synthetic 18 amino acid peptide derived from a consensus sequence of Annexins has been investigated by 1H NMR. Full sequential assignment has been achieved. Conformational properties of the peptide were deduced from the analysis of J(NH-CH alpha) coupling constants, amide proton exchange, 2D NOESY connectivities and computer modeling. PMID- 1517012 TI - Cyclo(L-prolyl-L-N-methylphenylalanyl). Conformation in solution and in the crystal. AB - Detailed analysis of the proton and carbon-13 NMR spectra of cyclo(L-prolyl-L-N methylphenylalanyl) in chloroform and methanol in relation to its nonmethylated analog provided information on the conformation of the title compound in solution as well as on the effect of N-methylation and solvation. The X-ray structure of the title compound in the crystalline state showed the same conformational features as the solution structure. The phenyl group folds over the diketopiperazine ring which resembles a flattened half-chair. Both amide bonds are considerably nonplanar. The pyrrolidine ring of proline shows a strong pucker at the ring junction with the largest chi 5 value hitherto observed. PMID- 1517013 TI - Search for peptide immunogens of the beta-subunit of human chorionic gonadotropin (hCG) capable of eliciting hormone specific and neutralizing antisera. Identification of an undecapeptide eliciting hCG-specific antisera. AB - The work reported herein describes our attempts to identify peptide immunogens of the beta-subunit of the pregnancy-specific placental hormone, human chorionic gonadotropin (hCG), capable of eliciting hormone specific and neutralizing antisera. Hydrophilicity profiles of the beta-subunits of hCG and the homologous pituitary hormone, human luteinizing hormone (hLH) were compared and two sequences which are hydrophilic but unique to hCG-beta were identified. They are 6-12 and 109-119 of hCG-beta. Results of the studies with the undecapeptide 109 119 of hCG-beta are reported in this paper. The undecapeptide amide was synthesized using the p-(acyloxy) benzhydrylamine resin and antisera to the peptide were elicited in rabbits using the peptide-diphtheria toxoid conjugate. The peptide is highly immunogenic as both the rabbits responded with high titers of antibodies to the peptide. The antipeptide antibodies bound to hCG but not to hLH showing thereby that the region 109-119 of hCG-beta is a unique determinant of hCG. However, the antibodies were found not to neutralize the biological activity of hCG. PMID- 1517014 TI - 14-membered cyclic opioids related to dermorphin and their partially retro inverso modified analogues. I. Synthesis and biological activity. AB - As a continuation of our program to study structure-activity relationships of opiate peptides, we report the syntheses and biological activities of a series of 14-membered cyclic dermorphin analogues closely related to enkephalin analogue Tyr-c[D-A2bu-Gly-Phe-Leu] incorporating a phenylalanine at the third position in place of glycine. In addition to two parent dermorphin analogues Tyr-c[D-A2bu-Phe Phe-(L and D)-Leu], four stereoisomeric retro-inverso modified analogues Tyr-c[D A2bu-Phe-gPhe-(S and R)-mLeu] with a reversed amide bond between residues four and five, and Tyr-c[D-Glu-Phe-gPhe-(L and D)-rLeu] with two reversed amide bonds between residues four and five, and between residue five and the side chain of residue two have been synthesized. The results from the guinea pig ileum (GPI) and mouse vas deferens (MVD) assays show that all analogues are superactive at either one or both opiate receptors and in general display higher activities as compared to the corresponding enkephalin analogues with a glycine at the third position. Results from the in vitro biological assays and conformational analysis using 1H-NMR spectroscopy (adjoining paper) will provide useful information to understand the role of the Phe3 aromatic side chain in dermorphin, and that of the Phe4 aromatic side chain in enkephalin, on opiate activity since these cyclic dermorphin analogues contain two Phe residues at both the third and fourth positions. PMID- 1517015 TI - 14-membered cyclic opioids related to dermorphin and their partially retro inverso modified analogues. II. Preferred conformations in solution as studied by 1H-NMR spectroscopy. AB - The 1H-NMR studies were extensively carried out to elucidate preferred conformations of a series of 14-membered cyclic dermorphin analogues containing two phenylalanines at both the third and fourth positions, e.g., Tyr-c[D-A2bu-Phe Phe-(L and D)-Leu], Tyr-c[D-A2bu-Phe-gPhe-(S and R)-mLeu], and Tyr-c[D-Glu-Phe gPhe-(L and D)-rLeu]. The temperature coefficients of the amide proton chemical shifts, vicinal 1H-1H coupling constants for the NH-CH groupings, and nuclear Overhauser effects provided information regarding the preferred conformations of the backbones. The conformational preferences and flexibility of the side chains were also estimated from the vicinal 1H-1H coupling constants around the C-C beta and C beta-C bonds in the articulated side chains. A comparison of the results obtained was made with the results previously obtained for the corresponding enkephalin analogues containing a glycine at the third position. It was found that the replacement of the glycine with the phenylalanine at the third position increases the conformational flexibility of the molecules with an L-, or S-, residue at the fifth position but reduces the flexibility of the molecules with D , or R-, residue at the same position. The rotating frame nuclear Overhauser experiments gave direct evidence for compact conformations, with the Tyr side chain folding back over the 14-membered ring in Tyr-c[D-Glu-Phe-gPhe-rLeu], which displays relatively high selectivity for the delta-receptor over the mu-receptor. This observation is in agreement with our model proposed for the cyclic enkephalin analogues: folded forms with close aromatic ring placement are required for the activity at the delta-receptor. PMID- 1517016 TI - Circular dichroism of reduced and oxidized recombinant human epidermal growth factor. AB - To further elucidate the role of the disulfide bonds in determining the protein folding of recombinant human epidermal growth factor (r-HuEGF) we studied the structure of reduced and oxidized r-HuEGF using circular dichroism (CD). The far UV CD spectrum of reduced r-HuEGF in 10 mM sodium phosphate pH 3.0 is very different from that of the oxidized molecule. The spectrum of the reduced molecule consists of a plateau from 225 to 200 nm, consistent with the presence of alpha-helix, beta-sheet, and unordered structure. The addition of the alpha helix inducer trifluoroethanol to the reduced molecule resulted in an enhancement of alpha-helix, at the apparent expense of beta-sheet, while the oxidized molecule was unaffected by the presence of this reagent. Secondary structure predictions based on the amino acid sequence of EGF correlate most closely with the structure of the reduced molecule. From these results, it appears that the r HuEGF has a more regular secondary structure in the absence of the disulfide bonds than in their presence. This suggests that the folding of EGF occurs by destroying the regular secondary structure that was present in the reduced state, and that the structure of the native molecule is dictated largely by disulfide bonding. PMID- 1517017 TI - Hydrogen bond connectivity patterns and hydrophobic interactions in crystal structures of small, acyclic peptides. AB - Crystal structures of all available unblocked linear peptides with two to five residues were retrieved from the Cambridge Structural Database and their intermolecular contacts and packing modes studied using molecular graphics. This survey reveals that interactions between hydrophobic portions of the molecules are critically important in determining the overall features of their crystal packing patterns. Distinct hydrophobic columns or layers are observed in almost all crystal structures. Analyses of the relationships between these interactions and crystal growth properties of small peptides are given. It is suggested that needle growth is promoted by hydrophobic packing, usually along a short crystallographic axis (4.6-6.0 angstroms). Also contributing to these morphologic characteristics are entropic factors associated with hydrophobic aggregation as well as tightly bound water molecules on hydrophobic faces. The paper also provides a comprehensive overview of hydrogen bond patterns in acyclic peptide crystals. It is demonstrated that one of their primary roles is to provide a scaffolding within which hydrophobic groups can aggregate. Even though there is a high density of hydrogen bonds in the crystals, often with complex patterns and networks, certain motifs are found to recur in a number of structures indicating specific hydrogen bond preferences. Water, for example, is an integral part of the hydrogen bond networks in these crystals, usually acting as the primary donor for main-chain carboxylate groups in peptide hydrates. PMID- 1517018 TI - Psychosocial and psychopathologic influences on management and control of insulin dependent diabetes. AB - The objective of this research was to explore the relationship of psychosocial variables to management and control of insulin-dependent diabetes, as measured by a scale of reported behavioral adherence and by glycosylated hemoglobin, respectively. The method includes a relatively large sample (127 subjects) drawn from a clinic, a broad range of psychosocial variables (depression, anxiety, family process, health locus of control), and documented reliability and validity of psychosocial measurement (alpha coefficients ranging from .63 to .95). The results show that both anxiety and depression have weak positive correlations with blood sugar. Family process variables also are weakly correlated with blood sugar. The measure of behavioral adherence is moderately correlated with blood sugar. The life stage of the diabetic appears to affect these relationships markedly. The conclusion is that there is no broad strong association of psychosocial variables with blood sugar but that there may be subgroups of diabetics, especially adolescents with recent onset, for whom the relationships may be more powerful. PMID- 1517019 TI - High "need for control" as a psychological risk in women suffering from ischemic stroke: a controlled retrospective exploratory study. AB - The assumption is tested that women scoring high on dimensions of coping pattern termed "need for control," which underlies several of the components of Type A behavior, are at increased risk of ischemic cerebrovascular disease. Consecutively admitted patients to medical wards, nineteen with ischemic cerebrovascular disease, were compared with nineteen patients with non arteriovascular disease and nineteen healthy females doing volunteer hospital work. "Need for control" was assessed by a psychometric test based on forty-five dichotomous items defining six unidimensional scales. The Bortner Type A behavior was filled out by the subjects and by their next of kin for an impression of the subject. In ANOVA the dimensions "work commitment, hard driving" (F = 6.87, p less than .002), "perfectionism, need for making plans" (F = 6.26, p less than .003), and "inability to withdraw from work obligations" (F = 3.89, p less than .02) differentiated the three groups in the expected direction. Duncan multiple range test resulted in very similar, significant findings, as did Bortner measures, filled out by a next of kin (F = 4.63, p less than .01). In all analyses, effects of age, current smoking, and coronary artery disease (CAD) were controlled. Our results suggest that high "need for control" defines a psychological risk in women suffering from ischemic stroke. Prospective studies should be undertaken. If they confirm our results, interventions aimed at modifying the "need for control" should be planned. PMID- 1517020 TI - Provocation of pseudoseizures by psychiatric interview during EEG and video monitoring. AB - OBJECTIVE: This paper discusses a new technique for diagnosing pseudoseizures. The technique consists of an intensive psychiatric interview designed to provoke a pseudoseizure during EEG and video monitoring. We wished to determine the overall efficacy of the technique and learn how our patients felt about having undergone the procedure. We were also interested in whether their seizures persisted approximately three years later. METHOD: We reviewed medical records and conducted telephone interviews with thirty of thirty-two patients who had previously undergone the procedure as part of an evaluation for unusual or intractable seizures. All evaluations had been performed on a university hospital neurology service. The patients were consecutive referrals to the consultative psychiatry service for suspicion of pseudoseizures. RESULTS: Nineteen of the thirty-two patients interviewed had a pseudoseizure under EEG and video monitoring. Of the thirty reached by telephone for follow-up, twenty-two recalled the procedure as helpful or benign. None regarded the overall psychiatric consultation negatively. Among the patients who had exhibited pseudoseizures there was a variety of psychiatric diagnoses with a preponderance of personality disorders. Two thirds of those patients without coexisting epilepsy stopped having seizures or rarely had seizures following their evaluations. CONCLUSIONS: The diagnostic technique described here is useful in patients with possible pseudoseizures. It does not appear to be harmful when employed as part of a comprehensive psychiatric consultation. How it may compare with other methods of pseudoseizure diagnosis will have to be determined by further study. PMID- 1517021 TI - Psychological profile of somatizing patients attending the integrative clinic. AB - OBJECTIVE: A clinic to evaluate and treat referred somatizing patients was established in the medicine clinic of a university medical center. METHOD: Fifty four patients were evaluated and compared to an age- and sex-matched non somatizing patient group. RESULTS: Somatizing patients had increased rates of psychiatric and alcohol and substance abuse histories. Somatizing patients scored high on all subscales of the SCL-90 and were most frequently found in the Anxious/Moody Cluster of the MBHI. These patients also endorsed highly beliefs in medical problems as a focus of their lives. CONCLUSIONS: These patients' psychological beliefs set the stage for conflict in the medical setting. The implications of these results are discussed in relation to liaison clinics, early identification, and treatment approaches. PMID- 1517022 TI - A prospective study of the effectiveness of brief professionally-led support groups for infertility patients. AB - OBJECTIVE: This study prospectively evaluates the effectiveness and patient acceptability of professionally-led support groups in alleviating psychologic distress in infertility patients. METHOD: Sixty-four consecutive patients in a university hospital infertility program were administered a battery of psychologic tests before and after attendance at an 8 weekly session support group. The comparison group consisted of 35 consecutive infertility referrals to the same unit who were not initially offered the support group and were similarly tested over an 8 week period. RESULTS: Support group patients had significantly greater (p less than or equal to 0.01) entry than exit scores on several measures of psychologic distress and depression (the Beck Depression Inventory, the Hamilton Rating Scale for Depression, and the Global Severity Index, Anxiety, Depression, Hostility and Obsessive Compulsive Subscales of the Brief Symptom Inventory). The Avoidance Coping Style on the Moos Coping Responses Inventory was correlated with a higher Global Severity Index (p less than or equal to 0.01). Comparison group patients had similar psychometric scores to the support group patients at entry but showed no change over 8 weeks. Attenders expressed a high rate of satisfaction with the support group. CONCLUSIONS: Professionally-led support groups are a highly acceptable and effective intervention in self referred patients in alleviating psychological distress related to infertility. PMID- 1517023 TI - A brief depression scale for use in the medically ill. AB - OBJECTIVE: Using items from two existing depression scales, we have sought to develop a brief self-rated instrument for detecting major depressive disorder (M.D.D.) in medically ill, hospitalized patients. METHOD: Forty-two items from the Geriatric Depression Scale (G.D.S.) and Carroll Depression Scale were administered to 559 men under age 40 or over age 70 consecutively admitted to the hospital. Eighty-two M.D.D.'s were diagnosed in this group by structured psychiatric interview. After eliminating 12 items confounded by medical illness, 11 items were selected using regression analysis, correlation with the total score, and factor analysis. The 11-item scale includes an assessment of the five DSM-III-R criteria for M.D.D. which are least confounded by medical illness (mood, suicidal intent, guilt or worthlessness, concentration, and psychomotor agitation). The scale was then tested in 78 medical inpatients who were later assessed for M.D.D. using a structured psychiatric interview. RESULTS: Ten out of twelve M.D.D.'s were identified (83% sensitivity) and depression excluded in 51 of 66 non-depressed subjects (77% specificity) (compared with 82% sensitivity and 76% specificity for the 30-item G.D.S.). Scores on the 11-item scale were also correlated with the G.D.S. (.92), the Zung Depression Scale (.58), and the C.E.S. D (.67). CONCLUSION: The 11-item scale is a practical tool for clinicians who screen patients for depression and for investigators who need a brief measure of depression in studies involving medical inpatients. PMID- 1517024 TI - Nursing evaluation: purposes, achievements and opportunities. AB - Evaluation has become a powerful, specialized discipline in recent decades, with its own sophisticated conceptual and technical apparatus. Evaluation of nursing has benefited strongly from these developments, as examples of cogent, recent evaluations demonstrate. Evaluation is already proving an indispensable practical tool for raising the quality of health care, and for advancing professional nursing standards. Nonetheless, there is room for further improvement. Neglected areas of nursing should be brought under the spotlight of evaluation, conceptual and methodological rigour should be strengthened, and training in research skills should be extended. PMID- 1517025 TI - Evaluating computer assisted learning for renal patients. AB - Healthcare professionals have become increasingly concerned with evaluating the impact of their interventions. Consumerism, quality initiatives and financial constraints have contributed in large measure to this concern. Consequently, the focus of many studies which involve the introduction of new and untried techniques is often on demonstrating their relative usefulness. This study sought to evaluate the usefulness and acceptability of computer assisted learning (CAL) for use in the education of renal patients on continuous ambulatory peritoneal dialysis. However, several problems were encountered which limited or impaired the evaluation process. We describe these problems and use them to illustrate the difficulties inherent in evaluative research. PMID- 1517026 TI - Health visiting: action research in a controlled environment. AB - The nature of health visiting is discussed. It operates in a radically different way from any of the curative services. Research into the effectiveness of health visiting must therefore take into account the many differences in context, in professional goals and in the nature of the interaction between health visitors and their "clients", compared with the work of the curative professions within their more controlled and controlling environments. The evaluation of one large scale health visitor intervention study is used here to highlight these differences. Health visiting research needs to free itself from the attempts by some to apply the laboratory model of evaluation, if it is to develop a corpus of "action research" thinking which reflects its more human and developmental characteristics. PMID- 1517027 TI - Issues in the evaluation of small-scale adult day care programs. AB - Evaluation of health care programs is a complex process which presents many challenges. A case study of a small-scale adult day care program evaluation is presented to illustrate these issues. The rationale for developing the program and the findings from the evaluation study are discussed. Several evaluation issues including the use of multiple methods, levels of analysis, characteristics of the sponsoring agency, political influences, methodological issues and influences on utilization of findings are addressed. PMID- 1517028 TI - Piloting an evaluation of triage. AB - This paper takes a broad view of the work involved in pilot studies of evaluation research. Drawing on their experience of preparation for a field experiment in a British Accident and Emergency department, which was to evaluate the effectiveness of a nurse triage system, the authors stress the importance of careful observation of the system to be studied, in the environment in which it is to be studied. In addition, the usual evaluations of research instruments which comprise formal pilot studies are included. PMID- 1517029 TI - Evaluation in mental health services: some quality assurance models. AB - This paper examines the context in which a concern for evaluation in mental health services has emerged. Quality assurance activities are seen as the main method of evaluating such services at the present time. A distinction is made between internal and external approaches to quality assurance and an example of each method is examined for its strengths and weaknesses. Successful quality assurance programmes are seen as being dependent on an amalgamation of these two approaches and two generic systems which adopt this method, "QUARTZ" and "Psychiatric Monitor" are considered for their strengths and weaknesses. It is suggested that evaluation strategies should be assessed for their capacity to promote organizational change. The increasing influence of the User movement is discussed. PMID- 1517030 TI - Survey of nursing quality assurance programs in selected hospitals in Alberta, Canada. AB - This study represents a survey of the nursing quality assurance programs in 12 hospitals in Alberta. The objectives of the study were: to identify the nature, content and costs of the programs, to determine the extent of nurse involvement in the design and operation of the programs, and the value and importance nurses place on their programs. The major findings of the study tend to support the view that the principles of organizational change theory have not been adequately addressed in terms of nursing quality assurance programs. Generally, nurses reported that they were insufficiently informed concerning their programs. Among the study recommendations is a call for improvements in the audit tools used, with greater emphasis being placed on the patient and the nurse providing the care and more decentralization of programs to the unit level to improve staff involvement and program relevancy. PMID- 1517031 TI - Evaluation of nursing education programmes--theory and practice. AB - In this paper, the history of educational evaluation is considered through a review of the literature, in order to try and understand how current evaluation methods have developed. It is important that a historical perspective is gained, as there has been a big shift in thinking from a strongly behaviourist code of practice to a more investigative and less prescriptive approach, during the relatively short time span that evaluation has had to develop as a subject in its own right. The application of the theory to practice is also considered in terms of a working evaluation model developed through work on continuing education courses in Scotland. PMID- 1517032 TI - Serum levels of vitamin A and retinol binding protein in chronic renal patients treated by continuous ambulatorial peritoneal dialysis. AB - The possible causes and consequences of hypervitaminosis A and retinol binding protein (RBP) levels were investigated in patients with chronic renal disease submitted or not to dialysis treatment. The study was conducted on 20 patients divided into two groups: 10 patients with chronic renal failure (CRF) treated by continuous ambulatorial peritoneal dialysis (CAPD), and 10 CRF patients with no dialysis treatment. Ten normal subjects formed the control group. Retinol levels were determined by HPLC, and RBP levels by immunoassay in plasma and in post dialysis fluid at different periods of time. Laboratory tests were carried out on all subjects, and dietary history was taken. Patients on dialysis had higher retinol levels than untreated patients. Retinol levels were found to be correlated with RBP levels. Serum retinol and RBP levels did not vary with diet, age or time of disease, dialysis group or time of dialysis, nor were they correlated with the levels measured in the dialysis fluid (CAPD). There was no significant correlation in retinol levels between chronic patients and controls. It is suggested that vitamin A and RBP clearances during dialysis do not accompany urea or creatinine clearance. Hypervitaminosis A did not show any toxic effect. PMID- 1517033 TI - Effects of dietary retinol on hepatic retinol storage and on plasma and tissue alpha-tocopherol in pigs. AB - A feeding experiment was carried out with pigs to investigate the effects of graded dietary retinol supplements on hepatic and plasma retinol and on alpha tocopherol in plasma and selected tissues. Four groups of twelve weanling pigs each with a mean body weight of 7 kg were fed a complete ration containing 54 IU vitamin E/kg and supplemented with 5, 10, 20 or 40 x 10(3) IU retinol/kg for Treatments 1 to 4, respectively. The feed was fed in restricted amounts for 150 days when the pigs were slaughtered at 105 kg body weight. Overall daily body weight gain and feed conversion ratio were 660 g and 2.49, respectively, without treatment differences (p less than 0.01). Hepatic retinol concentration (y, IU/g fresh weight) was linearly related to dietary retinol concentration (x, IU/kg feed) as expressed by y = -88.9 + 0.077 x [r2 = 0.94]. Total hepatic retinol (y, IU) and total retinol intake (x, IU) were linearly related as expressed by y = 194.9 x 10(3) + 0.4585 x [r2 = 0.98]. Hepatic retinol retention relative to intake ranged from 30.0% to 44.9%. Plasma retinol concentration was not affected by dietary retinol (p less than 0.01). Plasma alpha-tocopherol levels remained on a plateau for 42 days in all treatments. After 150 days plasma levels exceeded those at 42 days in Treatments 1 to 3, but not in Treatment 4. The effect of retinol on tissue alpha-tocopherol varied with tissues. While there was no effect on M. Longissimus and backfat, alpha-tocopherol levels in heart and liver showed an inverse relationship with dietary retinol.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1517034 TI - Tolerance of growing pigs for dietary vitamin A, with special reference to bone integrity. AB - Weanling crossbred pigs (144) of 8 kg initial weight were fed to 90 kg on diets containing graded levels of vitamin A representing 0, 1, 5, 10, 50 and 100 times the NRC (1988) estimated requirement. No clinical signs of deficiency or toxicity were recorded although plasma and liver retinol levels were affected by treatment. Histopathological examination indicated a high incidence of lesions in the cartilage of the distal femur and ulna, but they were not related to treatment. There was some evidence that excessive vitamin A levels in the diet significantly reduced the uronic acid concentration in joint cartilage, indicating a reduced concentration of proteoglycans. However no relationship was established between dietary vitamin A level and the incidence of clinical osteochondrosis. The results suggest that the allowable range of vitamin A set out in the Canadian feeds regulations is appropriate for practical pig production. PMID- 1517035 TI - Morphological changes in the tracheal epithelium of guinea pigs in conditions of "marginal" vitamin A deficiency. A light, scanning- and transmission-electron microscopic study under special breeding conditions appropriate to early vitamin A deficiency. AB - The aim of the study was to find out the influence of marginal vitamin A deficiency on morphological structures in the tracheobronchial epithelium in guinea pigs. The tracheobronchial epithelium of animals with vitamin A deficiency (n = 15) and control animals (n = 7), kept under optimal laboratory conditions, was evaluated by light and electron microscopy. The cellular ultrastructure was morphometrically analyzed. The height of the respiratory epithelium was slightly increased. The basal cells were arranged in a loose cell band of three to four layers. The quantity of cytofilaments in their cytoplasm was enhanced. Goblet cells were significantly reduced in vitamin A deficiency. There was also a significant decrease in their secretory granules. The number of ciliated cells was almost unchanged. They showed a significant reduction in mitochondria. The kinocilia often contained an atypical structure of the microtubules. Our findings confirm multiple ultrastructural dysplasias in early vitamin A deficiency which may lead to a disturbance of mucociliary clearance. PMID- 1517036 TI - Retinoid glucuronides do not interact with retinoid binding proteins. AB - Retinoid glucuronides have recently been described as water soluble, biologically active retinoids. In mouse mammary gland organ cultures retinoyl glucuronide, a retinoic acid counterpart, inhibited hormone induced differentiation. In this report we examined whether the effects of retinoyl and retinyl glucuronides are mediated by specific retinoid binding protein in mammary glands in organ culture. Results indicated that neither retinoyl nor retinyl glucuronide competed for cytosolic retinoic acid or retinol binding proteins respectively. These results indicate that either the effects of retinoid glucuronides are independent of retinoid binding proteins or they have to be metabolized to an active component which may in turn bind to retinoid binding protein for the glucuronide action. PMID- 1517037 TI - Zinc deficiency reduces hepatic cellular retinol-binding protein in rats. AB - Hepatic cellular retinol-binding protein (cRBP) levels were measured from the livers of four groups of Sprague-Dawley rats after three weeks of dietary treatment. The experimental group (n = 8) received a zinc-deficient (2.3 mg/kg dry powder) liquid diet ad libitum. A pair-fed control group (n = 8) received the same amount of liquid diet with supplemental zinc (60 mg/kg dry powder). Another control group (n = 8) received liquid diet ad libitum with supplemental zinc (60 mg/kg powder). A third control group (n = 7) received a pellet diet which also contained the same amount of zinc as the other control groups (60 mg/kg). Hepatic cRBP was reduced by more than 50% in the experimental group as compared to each of three control groups. It appears that zinc may be an essential element for the intra-cellular transport of vitamin A, in addition to its well-established role in the intercellular transport of vitamin A. PMID- 1517038 TI - Effect of ubiquinone-10 on fluctuation of beating rhythm of cultured myocardial cell sheets. AB - Effects of ubiquinone-10 (UQ-10) on fluctuation of beat time intervals and on beat frequencies were investigated in cultured ventricular myocytes obtained from mouse fetuses and quail embryos. Fluctuation rates of beat time intervals of mouse and quail myocardial cell sheets growing in the culture medium supplemented with 10% fetal bovine serum increased significantly to 1.2-fold and twice, respectively by removing serum from the medium. Beat frequencies of the cell sheets also significantly decreased simultaneously with the increase in the fluctuation rates. However, such changes of beating states were almost completely recovered within 10 min by addition of 100 microM UQ-10 as an isotonic lecithin emulsion to the medium. The addition of UQ-10 also significantly increased intracellular ATP content in the cell sheets concomitantly. These results suggested that UQ-10 circulating in serum may participate in the maintenance of regular and rhythmical beating of myocardial cells, presumably through stimulating intracellular ATP generating systems. PMID- 1517039 TI - Plasma ubiquinone, alpha-tocopherol and cholesterol in man. AB - Plasma ubiquinone, coenzyme Q10 or CoQ10 has been analyzed in plasma together with alpha-tocopherol and free cholesterol in healthy sedentary male subjects (SS), endurance trained male athletes (ET) and male patients with severe ischemic heart disease (IHD). Higher means were found in SS compared to both IHD and ET. Moreover, the ratios CoQ10 and alpha-tocopherol over free cholesterol were higher. In all groups significant relationships were found between the two products of the mevalonate pathway: CoQ10 and cholesterol (r ranged 0.66-0.86, p less than 0.01). The two lipophilic antioxidants, CoQ10 and alpha-tocopherol, were interrelated only in IHD (r = 0.86, p less than 0.001), borderline in SS (r = 0.51, p less than 0.05) but not in ET. It is assumed that plasma free cholesterol reflects the capacity to transport lipids and lipophilic compounds in blood. With metabolic stress and an elevated radical formation as in IHD and ET, the lower CoQ10 and alpha-tocopherol to cholesterol ratios mirror a subsequent toll on the scavenging potential. The difference in LDL levels between IHD and ET and the different storage capacity of CoQ10 and alpha-tocopherol might explain the tight coupling in IHD but not in ET. It is possible that the toll reflects both an intra- and extracellular radical quenching activity. The joint effect of the two lipophilic, extracellular antioxidants CoQ10 and alpha-tocopherol role in protecting e.g. LDL particles from peroxidation is suggested. PMID- 1517040 TI - The transport of thiamine, riboflavin and pyridoxal 5'-phosphate by human placenta. AB - In the present examination the concentrations of thiamine, riboflavin and pyridoxal 5'-phosphate in blood plasma of pregnant women and venous and arterial cord plasma were determined. In maternal plasma the concentration was 4.5 nmol/l (thiamine), 22.2 nmol/l (PLP), 8.7 nmol/l (free riboflavin) and 84.5 nmol/l (FAD + FMN). In venous cord plasma the concentration was 45.9 nmol/l (thiamine), 112.1 nmol/l (PLP), 40.6 nmol/l (free riboflavin) and 49.1 nmol/l (FAD + FMN). Therefore the gradients of concentration between maternal plasma and venous cord plasma were 1:10 for thiamine, 1:4.7 for free riboflavin and 1:5 for PLP. For the coenzyme forms of vitamin B2 the maternal circulation showed the higher concentration (1.7:1). Therefore an active transplacentar transport mechanism was assumed. The vitamin concentrations in cord arteria were significantly lower than that in cord vene, indicating a massive retention by the fetus. PMID- 1517041 TI - The impact of iron deficiency on the flux of folates within the mammary gland. AB - The purpose of the present study was to examine whether impaired milk folate secretion during maternal iron deficiency is due to an altered flux of folates within the mammary secretory cell. Specifically we sought to determine whether the folate substrates of methionine synthase and the products of folylpolyglutamate synthetase are altered during iron deficiency in vivo. Rats were fed diets containing 0.5, 2.0 or 7.0 mg/kg folate and 8(Fe-) or 250(Fe+)mg/kg Fe throughout gestation and lactation. On day 17 of lactation dams were milked and killed. The concentration of reduced, methylated (5-CH3-H4), nonmethylated short and long chain forms of folate in milk were determined using a differential microbiological technique. Total mean milk folate concentrations among Fe- dams fed 2.0 and 7.0 mg/kg folate were half that of Fe+ dams fed 2.0 and 7.0 mg/kg folate. Despite this, the relative proportion of reduced, 5-CH3-H4, short and long chain folates did not differ in milk from Fe+ or Fe- dams. Approximately 75% of milk folates were methylated. Only Fe+ dams fed 7.0 mg/kg folate produced milk containing significant quantities of incompletely reduced folates. In conclusion, activity of the mammary epithelial cell enzymes methionine synthase and folylpolyglutamate synthetase in vivo, are unaffected by iron deficiency and therefore are not responsible for the dramatic reduction in milk folate secretion. PMID- 1517042 TI - Relationship among the fatty acid composition of various lipid fractions in normally nourished German adults. AB - The relationship among the fatty acid (FA) composition of plasma cholesteryl esters (CE), plasma phospholipids (PL), total erythrocyte lipids, erythrocyte phosphatidylethanolamine (PE), erythrocyte phosphatidylcholine (PC), and total lipids of the subcutaneous fat (SCF) was investigated by parallel analyses of samples from 47 normally nourished German adults. Each lipid fraction revealed a characteristic FA pattern. A close relation between major FA in plasma lipids, especially in CE, and those in PC was found. The FA composition of PE, however, appeared to be more independent from plasma values. Of all FA in SCF only linoleic acid values showed a correlation to the values in CE and PC. It is concluded that, in clinical studies, FA analyses of total plasma lipids or total erythrocyte lipids fractions should be avoided in favour of separate analyses of various lipid fractions. PMID- 1517043 TI - Bile salt-independent retinyl ester hydrolase in the rat lacrimal gland. AB - The lacrimal gland secretes retinol and synthesizes and stores retinyl esters. In this study, presence of retinyl ester hydrolase in rat lacrimal gland was investigated. A bile salt-independent retinyl ester hydrolase was identified in lacrimal gland homogenates and microsomes which were incubated in a tris-maleate buffer with retinyl palmitate as substrate. Retinol produced was measured by HPLC and activity expressed as pmoles retinol produced/mg protein/hr. In homogenates, the enzyme activity had a pH optimum at pH 6 and maximum specific activity of 57.7 pmoles/mg/hr. In microsomes, the activity was optimal at pH 7 and maximum specific activity was 1073 pmoles/mg/hr. In contrast, rat liver retinyl ester hydrolase had a pH optimum at pH 8 and a specific activity of 24.7 pmoles/mg/hr. These observations demonstrate that a complete cycle of retinyl ester metabolism is present in the lacrimal gland. PMID- 1517044 TI - Pini as a mortality index in the hospitalized elderly patient. PMID- 1517045 TI - Vitamin A supplementation in malnourished Sudanese children. PMID- 1517046 TI - WHO/UNICEF issue statement on HIV and breastfeeding. PMID- 1517048 TI - The fundamentals of professional regulation. AB - Regulation or deregulation is becoming an increasingly important issue in society. Health care is one target in the debate about the nature, amount and locus of control necessary to ensure safe health services to all. As professionals responsible for providing a part of the essential health services, nurses are caught up in the movement. Therefore nursing has an obligation to understand and participate in the development, administration and monitoring of all types of regulatory controls that touch on nursing education and practice, and the healthcare services themselves. PMID- 1517047 TI - Nursing's next advance: an internal classification for nursing practice. AB - An International Classification of Nursing Practice (ICNP) is needed to support the processes of nursing practice and advance the knowledge necessary for cost effective delivery of quality nursing care. Below, the authors present their case for developing such a system that will provide nursing with a nomenclature, a language and a classification that can be used to describe and organize nursing data. It is their belief that this landmark project is achievable and that ICN should lead the work in collaboration with its member associations, the World Health Organization and key national, international, governmental and nongovernmental groups. But to ensure that the system will be adaptable across borders, nurses and organizations are being encouraged to share their ideas and research on such a system. PMID- 1517049 TI - Cost-effective caring. AB - Cost containment is the key issue in healthcare systems and a key concept that nurses must grasp in this time of shrinking budgets and growing demand for health care. As healthcare budgets come under increasing scrutiny, nurses must prove their cost-effectiveness. To ensure the maintenance of quality care, national nurses' associations have a strong role to play in supporting research efforts into nursing's real worth (not only in cost terms) and gathering and disseminating this information to demonstrate the value of quality nursing. To get nurses worldwide to campaign for cost-effectiveness, ICN will focus on "Quality, Costs and Nursing" in its celebration of International Nurses' Day in 1993. PMID- 1517050 TI - Nurses: an image change still needed. AB - In Australia the image of nurses has not changed, despite advances in nursing practice, education and research. The stereotyped image affects how nurses practice and the future of the nursing profession. Below, a look at how the nurses' image affects nursing practice and suggestions on how this image can be improved. PMID- 1517051 TI - Operative fixation of unstable pelvic ring injuries in polytrauma patients. AB - Sixteen polytraumatized patients with a variety of unstable pelvic ring fractures were treated with operative fixation. We have found that an aggressive approach with adequate early stabilization of the pelvis offers many advantages over conservative management particularly in polytraumatized patients. PMID- 1517052 TI - Familial cryptogenic fibrosing alveolitis: a case report. AB - A family of seven siblings is described, all of whom, developed finger clubbing during their third decade. Three of the seven developed cryptogenic fibrosing alveolitis (CFA). Of the remaining four siblings, two have died prematurely from conditions possibly associated with cryptogenic fibrosing alveolitis. The youngest two siblings remain asymptomatic at present. This paper reports one of the most concentrated incidences of the rare familial form of CFA. PMID- 1517053 TI - Snuffles in infants--infection or autonomic dysfunction. AB - The presence of excess nasal mucus causing noisy nasal breathing with an obvious mucus discharge (snuffles) is a common problem in infants in the first three months of life. The presence of "snuffles" has traditionally been ascribed, unproven, to an upper respiratory tract infection despite there being no other signs of an acute infection in the majority of infants with "snuffles". To assess the possible role of impaired vasomotor control (autonomic function) in the pathogenesis of snuffles we measured the effect of a change from the supine to the upright position on resting blood pressure in 50 infants with "snuffles" and 50 healthy control infants. The mean age in both groups was 7 weeks post delivery, all infants were attending a well baby clinic for a routine examination, had no signs of an acute infection and none were on any medication (including nasal drops). A fall of greater than 10% of resting blood pressure was taken to indicate postural hypotension. Four of fifty infants in the control group compared to 22 of 50 in the snuffles group demonstrated postural hypotension (Chi square 16.84, p less than 0.001). The results suggest that in some infants "snuffles" may be associated with impaired vasomotor control. PMID- 1517054 TI - Classical caesarean section through the posterior uterine wall. AB - We report a case of myomectomy and classical caesarean section through the posterior uterine wall necessitated by 180 degrees dextro-rotation of a gravid uterus with large fibroids. The non-specific clinical course and rarity of pathological torsion of the gravid uterus makes the preoperative diagnosis difficult. Ultrasound recognition antenatally of a fibroid changing its position should help with the prediction preoperatively of uterine rotation. PMID- 1517055 TI - Splenic pseudocyst: aspiration or cyst decapsulation. AB - A 12 year old boy with a splenic pseudocyst is reported. Percutaneous drainage resulted in complete emptying but rapid reaccumulation. Cyst decapsulation with splenic preservation was curative and is recommended for definitive therapy of splenic pseudocysts. PMID- 1517056 TI - Foreign body complications of central venous catheterisation in critically ill patients. AB - In three critically ill patients, central venous catheter--associated foreign bodies were identified while the patients were in the intensive care unit. Two patients had fragments of retained catheter; in the third patient a guide-wire was lost within the vascular tree. The catheter fragments were associated with clinical symptoms while side effects were not observed with loss of the guide wire. All three foreign bodies were removed without complications. PMID- 1517057 TI - Hyperhomocysteinaemia: a risk factor for extracranial carotid artery atherosclerosis. AB - Hyperhomocysteinemia arising from impaired methionine metabolism, and usually due to a deficiency of cystathionine beta-synthase is a significant and independent risk factor for symptomatic vascular disease. It is not known if hyperhomocysteinemia in apparently healthy asymptomatic subjects is associated with atherosclerosis and whether such a relationship is independent of conventional risk factors. The prevalence of asymptomatic extracranial carotid artery atherosclerosis was determined by duplex ultrasound examination in 25 obligate heterozygotes with respect for cystathionine beta-synthase deficiency (whose children were known to be homozygous for this genetic defect) and in 21 controls. Hyperhomocysteinemia was determined by a standard methionine-loading test and conventional risk factors were also recorded. Twelve of 25 obligate heterozygotes and 8 of 21 normal controls had evidence of extracranial carotid artery atherosclerosis. Hyperhomocysteinemia as a genetic trait was not a significant risk marker, but the actual homocysteine level was associated with an increased risk of carotid disease. After adjustment for the effects of other significant risk factors, the odds ratio of hyperhomocysteinemia for carotid disease was 1.038 per unit increase in homocysteine level (P = 0.03). Hyperhomocysteinemia is a weak risk factor for asymptomatic extracranial carotid atherosclerosis and the relative risk associated with this genetic trait is less than that observed in a study of patients presenting with clinical manifestations of vascular disease. PMID- 1517059 TI - Tuberculosis in the west of Ireland 1986-1990. AB - A review of mycobacteria isolated from clinical samples from the Western Health Board Area (WHBA) for the years 1986 to 1990 was performed to establish the pattern of mycobacterial infection. The incidence of microbiologically proven cases of tuberculosis (13.3/100,000) and of sputum smear positive cases (6.2/100,000) was determined and correlated with notification data. M. bovis accounts for 6.3% of cases of microbiologically confirmed tuberculosis in this area. Resistance to one or more of the first line anti-tuberculous drugs was noted in 5.3% of isolates (excluding pyrazinamide resistance in M. bovis). Clinically significant isolates of mycobacteria other than tuberculosis (MOTT) were rare throughout the five year period. The overall incidence of microbiologically proven cases of tuberculosis is relatively high and M. bovis and drug resistant isolates of M. tuberculosis are relatively common. PMID- 1517058 TI - Normal bone density in Irish women: is American normative data suitable for use in Ireland? AB - The objective of the study was to determine whether or not U.S. normal data for female Vertebral Bone Mineral Density is suitable for use in an Irish population. One hundred and fifty-six healthy Caucasian women of permanent Irish domicile had bone densitometry performed using single energy quantitative computed tomography of L2, L3 and L4 vertebrae. We found that comparison of our results to normal American data shows a slight and progressive increase in bone mineral content of postmenopausal American women with age relative to the Irish population. This difference is small and not sufficient to justify development of separate normal values for Irish women. We conclude that this discrepancy may be due to a combination of environmental and racial factors or to the more rigorous exclusion criteria applied in our study. PMID- 1517060 TI - Audit of full blood count monitoring in patients on longterm gold therapy for rheumatoid arthritis. AB - The use of injectable gold in the treatment of rheumatoid arthritis (RA) is hampered by the high incidence of adverse reactions of which myelotoxicity is potentially the most serious. Regular full blood count (FBC) monitoring prior to each injection, a practice which requires much time and effort, has never been fully evaluated. Of 154 patients who were started on gold and followed by the lifetable method for up to 10 years, five patients were withdrawn from treatment because of myelotoxicity, thrombocytopenia in all cases: the two most serious cases occurred early at 3 and 7 months after starting treatment; three mild cases occurred at 17, 37 and 60 months, were of slow onset and reversed spontaneously. Clearly, FBC monitoring is justifiable in the first two years of treatment when the incidence of adverse reaction is highest. Further investigation is required to justify this practice after two years of uncomplicated treatment. PMID- 1517061 TI - Alfred Parsons on suspected perforated gastric ulcer. 1892. AB - Alfred Parsons (1864-1952) was noted for his vigour of mind and body and Spartan habits and his dramatic teaching. In 1891 while a junior doctor he cared for three fatal cases of acute perforation of a chronic ulcer of the stomach. In May 1892 he made a passionate plea for early diagnosis and surgery in this condition. The first successful operation was performed in the same month by Ludwig Heusner in Germany. PMID- 1517062 TI - Irish Society of Gastroenterology. Abstracts. PMID- 1517063 TI - International incidence of central nervous system tumors in children. AB - A study of the descriptive epidemiology of central nervous system tumors in children aged 0-14 was undertaken using international incidence data referred to the period 1970-1984. The median incidence rates were found to be 23 per million for males and 19 per million for females. The median cumulative incidence rates were found to be 341 per million for males and 296 per million for females. Males had incidence rates that were about 20 per cent higher than those for females. Variation in incidence rates by age, sex, race, and geographic area are discussed. Data on possible genetic and environmental risk factors for these tumors are reviewed. PMID- 1517064 TI - Supplementation of polyunsaturated fatty acids in multiple sclerosis. AB - For several years polyunsaturated fatty acids (PUFAs) and in particular essential fatty acids (EFAs) have been proposed for the treatment of multiple sclerosis (MS). There are contrasting data in literature regarding the effects of the n-6 and the n-3 PUFA series on different aspects of the disease, in particular on the frequency and severity of relapses and platelet function. This can be ascribed to the different criteria of patient selection in relation to the form and severity of disease at the beginning of the various studies. Till now authors have tended to consider the effect of PUFA supplementation only on some clinical aspects of the disease. Modification in the more sensitive indices (immunological or biochemical) of the disease activity should be taken into account and also the influence of dietary lipid intake by patients in relation to n-3 or n-6 EFA supplementation. PMID- 1517065 TI - Electrocardiographic changes in subarachnoid hemorrhage secondary to cerebral aneurysm. Report of 70 cases. AB - Electrocardiographic (ECG) alterations in the course of sub-arachnoid hemorrhage (SAH) have frequently been reported. The most frequent anomalies reported were lengthening of the QT interval, very negative or positive deep T waves, elevation or depression of the ST segment and the presence of U waves. We report 70 cases of SAH secondary to rupture of intracranial aneurysm (part of a larger group of 150) with ECG changes. We review the literature with particular regard to discussion of the possible pathogenesis of ECG changes and to the way they may affect the general clinical course. PMID- 1517066 TI - Nosology of spastic tetraplegic cerebral palsy: clinical review of fifty cases. AB - The aim of this study is to contribute to the definition of tetraplegic cerebral palsy (TCP) and to verify the classification criteria currently used by reviewing the clinical and neurological aspects of 50 children having non-progressive encephalopathy with neurological involvement of 4 limbs (symmetric 4-limb type, side-asymmetric type, upper-limb dominated type with or without dystonic traits). All severe diplegic patients, i.e. less upper than lower limb involvement and patients with dystonic hyperkinetic syndrome without spastic features were excluded. The data were supplied by the hospital records, evolution of motor performance and the presence or absence of epilepsy, visual problems, language disorders, intellectual impairment. All the children underwent: neurological examination, functional assessment, cognitive evaluation. Severe motor impairment was found in 80% of the patients, whose clinical characteristics led to a diagnosis of severe TCP or "true TCP" according to Hagberg, whereas 20% of them showed mild to moderate impairment with a more favorable prognosis. This group of patients complied with the classification of Michaelis who defined the quadrispastic CP types more broadly and delineated five subgroups also including cases with milder involvement (side-dominated, three-limb dominated tetraparesis). The intellectual assessment showed that, in the severely affected patients, only a small percentage had severe intellectual impairment (IQ less than 50, 37.5%), which contrasts with published data on this pathology, while the majority of the subjects showed moderate (25%) or mild intellectual impairment (32.5%) or normal cognitive function (5%).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1517067 TI - Italian neurologists and euthanasia: a poll. AB - We have tried to sound out Italian neurologists regarding their attitude to euthanasia, a very controversial issue today. We gave a short multiple-choice questionnaire to neurologists attending a national conference, asking their opinion on some issues related to euthanasia. 75 (25%) of the 300 doctors polled completed the questionnaire. Answers were often contradictory. A trend in favor of passive euthanasia among the respondents and a strong demand for guidelines are evident. Emotional rather than professional or rational factors seem to play a major role in the approach to this dilemma. PMID- 1517068 TI - Myasthenia gravis associated with Charcot-Marie-Tooth neuropathy: report of a case. AB - We report the case of a 24 year old woman who developed myasthenia gravis in the course of a mild form of Charcot-Marie-Tooth neuropathy. We describe the clinical manifestations together with the neurophysiological, pathological, serological findings and response to therapy and discuss the unusual association in the light of the relevant literature. PMID- 1517069 TI - Neurogenic pulmonary edema: a presenting symptom in multiple sclerosis. AB - Altered cardiovascular and respiratory function is uncommonly encountered in multiple sclerosis, though it may appear late in the course of the disease [4]. Episodes of acute ventilatory failure due to autonomic and/or voluntary respiratory function paralysis have already been described. These episodes are often accompanied by a focal neurological deficit which expresses lesion at the level of the medulla [6]. A demyelinating bulbar lesion leading to altered cardiovascular function is likewise infrequent but when it happens, bradycardia, postural hypotension [2], or acute pulmonary edema without heart failure may occur [1]. We present a case of non cardiogenic acute pulmonary edema which had neither a toxic insult nor an infective agent as etiology, but appeared as the initial manifestation of a multifocal demyelinating syndrome. PMID- 1517070 TI - A case of successful pregnancy in a woman with Friedreich ataxia. AB - We report on a 34-year-old woman with advanced FA who achieved a successful pregnancy. The neurological and cardiological features of the disease remained unchanged during and after pregnancy. Because of a slight respiratory impairment, which appeared at the 6th month, cesarean section was performed at the 34th week. FA is not necessarily a bar to successful pregnancy, but early referral to a cardiologist and respiratory monitoring is mandatory. The risk of transmission of the disease for our couple was 1/95.5 compared with 1/36.000 for a non-affected couple. PMID- 1517071 TI - Left temporal glioma presenting as migraine with typical aura. PMID- 1517072 TI - Migraine without aura and ischemic stroke. PMID- 1517073 TI - Starting from the bottom up. PMID- 1517074 TI - Rabid bat diagnosed in Hawaii. AB - Since 1966, the Hawaii State Government has been conducting Fluorescent Rabies Antibody (FRA) testing on animal brains as part of a statewide rabies surveillance program. On April 3, 1991, the Department of Health (DoH) laboratory diagnosed the first case of rabies detected in the State. A large brown bat, Eptesicus fuscus fuscus, captured in a transport container that had just been off loaded from a ship at Honolulu harbor, was caught. It's brain was examined and showed typical fluorescent staining patterns for rabies virus. The USPHS Centers For Disease Control (CDC) rabies laboratory confirmed the diagnosis 2 days later. The successful interception of this rabid animal was the result of close cooperation between the private sector (Sea Land Service, Hawaiian Stevedores) and the Hawaii State Government Departments of Health and of Agriculture. PMID- 1517075 TI - Elimination of preventable blindness from diabetes by the year 2000. AB - "Diabetes 2000" will parallel a major diabetic retinopathy public information campaign recently announced by the National Eye Institute. The NEI's National Eye Health Education Program (NEHEP), which targets both diabetic retinopathy and glaucoma, is fashioned along the lines of earlier federal initiatives against smoking and high blood pressure. By continuously updating our medical knowledge and skills related to this multisystem disorder, and by forging partnerships between physicians in the effective and efficient management of diabetic patients, we have a unique and important opportunity--we can reduce preventable blindness from diabetes by the year 2000. PMID- 1517076 TI - Lymph node metastasis in squamous cell carcinoma of the oral cavity: correlation between histologic features and the prevalence of metastasis. AB - A retrospective study was made of the correlation between preoperative clinical or histologic findings and the prevalence of lymph node metastasis in 60 patients with squamous cell carcinoma of the oral cavity who had histologically confirmed neck metastasis. Of these 60 patients, 39 with clinically N+ necks underwent immediate therapeutic neck dissection, and 21 whose necks were initially N0 but progressed to N+ during observation underwent subsequent therapeutic neck dissection. The primary site, TNM staging, histologic grade of malignancy of biopsy specimen, and location and number of histologically positive lymph nodes were reviewed in each case. The results were as follows: (1) The prevalence of neck metastasis was not significantly correlated with primary site and T stage; however, there was an apparent correlation between histologic grade of malignancy and the prevalence of neck metastasis. Patients with grade I-II histologic malignancy showed limited metastases that involved lymph nodes in levels I-II. On the other hand, patients showing grade III-IV histologic malignancy often had metastases that extended beyond level III, regardless of T stage. These results suggest that histologic grade of malignancy, as well as clinical features, must be taken into consideration when deciding whether supraomohyoid neck dissection is indicated. (2) The group that underwent subsequent neck dissection exhibited less advanced neck metastasis and a better prognosis than the group which underwent immediate neck dissection. These findings show that if they are closely followed up, it is possible to delay neck dissection in N0 patients until a neck metastasis is detected. PMID- 1517077 TI - Thyroid and parathyroid surgery without drains. AB - The question of routine wound drainage after thyroid and parathyroid surgery remains controversial among experienced surgeons. Review of the literature failed to reveal any study that established the benefit of drainage after thyroidectomy and parathyroidectomy. A retrospective review of 139 thyroid or parathyroid procedures performed without drainage was conducted. One hundred ten thyroid operations were performed, including unilateral lobectomy with isthmusectomy [82 (74.5%)], total or bilateral subtotal thyroidectomy [26 (23.6%)], and isthmusectomy [2 (1.8%)]. Histologic examination yielded a benign diagnosis in 94 specimens (85.4%); 16 specimens (14.5%) contained thyroid carcinoma. Parathyroid explorations were performed in 29 patients (20.8%) all of whom had adenomas. Postoperatively, there were no instances of wound hematomas, infections, or rebleeding necessitating reoperation. Minor complications included asymptomatic wound seromas (4-30 mL) in five (3.6%) patients, which were aspirated 2 weeks after discharge without further recurrence. This minimal complication rate of 3.6% with undrained neck incisions suggests that routine prophylactic drainage of thyroid and parathyroid wounds is unnecessary. PMID- 1517078 TI - Bone and gallium scans in postradiotherapy osteonecrosis of the jaw. AB - The role of radiographic and nuclear imaging in evaluation of postradiotherapy osteonecrosis of the jaw was studied. Patients who had received imaging at diagnosis and following hyperbaric oxygen therapy were studied. Radiographic changes did not correlate with the clinical status of patients. All bone scans were abnormal at the time of diagnosis of osteonecrosis, but remained abnormal following changes in the clinical status of patients. Thus, the bone scan may aid in the detection of osteonecrosis. Gallium uptake did not aid i diagnosis, but did correlate with clinical findings following treatment. Persisting positive gallium scans may indicate the need for surgery following hyperbaric oxygen therapy. PMID- 1517079 TI - Epidermoid cysts of the cranial bones. AB - Ectodermally derived tissue in ectopic sites is seen in the head and neck. Extracranial dermoid and epidermoid tumors are relatively rare. While most otolaryngologists are familiar with the cholesteatoma of the otic area, not very many are exposed to this lesion in other sites. Those of the cranial bones are even rarer still. These tumors may expand (1) laterally in the cranial bones, (2) externally to present as masses in the scalp or facial region, or (3) internally to involve the intracranial contents. A patient with a frontal bone epidermoid, whose tumor had expanded in all three directions to erode both inner and outer cortex of cranium and laterally to rupture into the frontal sinus, is discussed. The literature is reviewed and the management of these rare masses is discussed. PMID- 1517080 TI - Postoperative radioactive iodine evaluation of total thyroidectomy for thyroid carcinoma: reappraisal and therapeutic implications. AB - The records of 430 patients who underwent total thyroidectomy with radioactive iodine (RAI) uptake studies performed postoperatively were reviewed. Indications for the administration of an ablative dose of iodine 131 are given. The majority (85.4%) had no or low (less than 2%) evidence of focal uptake and therefore were not treated with ablative doses of iodine 131. RAI scanning is necessary postoperatively to determine the completeness of the surgical procedure and to detect residual or metastatic disease. Small foci of residual disease or occult distant metastases can be adequately treated with therapeutic doses of RAI. Nodal or distant metastases that become clinically evident following thyroidectomy are usually not successfully treated with RAI. PMID- 1517081 TI - Embolization of the ophthalmic artery for control of epistaxis: report of two cases. AB - Embolization of the internal maxillary artery, an accepted method for control of severe or recurrent posterior epistaxis, usually involves the ipsilateral artery, but occasionally the contralateral vessel and the facial arteries as well. Such endovascular treatment may fail if the vascular supply to the bleeding vessels originates in derivative branches of the ophthalmic artery. We report two unusual cases in which embolization of the ophthalmic artery was performed to control epistaxis. The first patient had a prosthetic eye. In the second, sight in one eye was sacrificed after careful consideration in order to prolong life. PMID- 1517082 TI - Papillary adenocarcinoma in thyroid hemiagenesis. AB - Variation in the gross anatomy of the thyroid gland is relatively common. Although thyroid hemiagenesis is felt to be a rare anomaly, its incidence is probably underestimated as the diagnosis is usually incidental. The case of a 41 year-old woman with right thyroid hemiagenesis associated with papillary adenocarcinoma is presented. The diagnosis of hemiagenesis was established by isotope imaging and surgical exploration for a benign nodule. Seven years later she was seen with a recurrent neck mass, and an isotope scan revealed it to be a cold thyroid nodule. As she was diagnosed to have papillary adenocarcinoma, total thyroid lobectomy was performed and at present she remains disease-free. PMID- 1517083 TI - Glandular odontogenic cyst. AB - Two cases of glandular odontogenic cysts are reported. The unique histological features, eg, the intraepithelial glandular structure, papillary processes, and eosinophilic cuboidal and larger granular superficial cells are sufficient to warrant glandular odontogenic cyst as a distinct entity. Electron microscopic examination of the superficial eosinophilic cuboidal cells are suggestive of a process similar to apoptosis. Eroded cortical plates suggest an aggressive behavior. PMID- 1517084 TI - Hamartomas of the nose and nasopharynx. AB - Hamartomas are easily diagnosed entities when occurring in the lung and gastrointestinal tract. In the nose and nasopharynx, where such lesions are rare, biopsy of a hamartoma containing epithelial proliferation may lead to a misdiagnosis of cancer, with resultant radical and deforming surgery, particularly if they present in adulthood. We encountered three such lesions over 2 years in the Massachusetts Eye Ear Infirmary, and another was retrieved from the recent files. All presented with nonspecific obstructive symptoms of the nose or nasopharynx, and were treated by resection. Follow-up is short, (4 months to 1 year), but in no case has there been recurrence. The clinical diagnosis was malignancy in 2 cases, inflammatory polyp in one. PMID- 1517085 TI - Precise localization of the marginal mandibular nerve during neck dissection. PMID- 1517086 TI - Neuroendocrine tumors of the larynx. PMID- 1517087 TI - Patient on-line access to medical records in general practice. AB - Many patients want more information about health and the computer offers tremendous potential for interactive patient education. However, patient education and the provision of information to patients will be most effective if it can be tailored to the individual patient by linkage to the medical record. Furthermore the Data Protection Act requires that patients can have access to explained versions of their computer-held medical record. We have examined the practicality and possible benefits of giving patients on-line access to their medical records in general practice. Seventy patients (20 males; 50 females) took part in the study. Sixty five of these used the computer to obtain information. The section on medical history was most popular, with 52 people accessing it. More than one in four of the problems were not understood until the further explanation screen had been seen. One in four also queried items or thought that something was incorrect. Most patients obviously enjoyed the opportunity to use the computer to see their own medical record and talk to the researcher. Many patients commented that because the General Practitioner (GP) didn't have enough time, the computer would be useful. Sixty one (87%) (95% CI: 79-95%) thought the computer easy to use and 59 (84%) would use it again. This is despite the fact that 43 (61%) thought they obtained enough information from their GP. This small study has shown that patients find this computer interface easy to use, and would use the computer to look at explanations of their medical record if it was routinely available.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1517088 TI - Survey of the implementation of workplace alcohol and smoking policies among employers in Fife. AB - A survey of major employers in Fife shows that at present 33% of respondents have implemented written alcohol policies, while 40% have implemented written smoking policies. A total of 19% have both alcohol and smoking policies in place. The initiative for policy development appears to have arisen mainly from management, but trade unions and management have co-operated well during policy formulation. The majority of policies have been implemented for more than three years. A small number of companies in Fife appear to be interested in the development and implementation of written alcohol and smoking policies in the workplace. PMID- 1517089 TI - Socio-economic factors associated with HIV infection in pregnant women. AB - The HIV epidemic in women in Edinburgh has characteristics which enable a total population study. We studied retrospectively all women with a known history of injection drug use or with a seropositive drug-using partner in a five year period from 1985-1990. We sought to quantitate lifestyle and environmental factors associated with HIV infection in pregnant women and to test two hypotheses: that infected women would have more adverse socio-economic features, and that there would be a change in these factors with time. There were 244 pregnant women in the study. They were slightly younger than all Edinburgh City women and much less likely to be married. They were much more likely to live in areas of multiple housing deprivation. Only 16% of women, and 28% of partners, were in paid employment; 90% of women smoked and 76% had a history of injection drug use. Some 28% of previous children were in the care of another, often a relative, 8% of women had a recent prison admission, and 58% of those tested had antibodies to Hepatitis B. Univariate analysis showed that none of these factors was significantly different in HIV seropositive women except for prison admission, previous infection with Hepatitis B, which probably all related to type of drug use. Linear logistic regression suggested two other variables which distinguished between groups, but because these are composite, and dependent on incomplete data, this must be interpreted with caution. The same overall associations were found when only women with a history of injection drug use were considered. There was no statistically significant change in these factors with time.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1517090 TI - Collaboration between geriatricians and general surgeons. AB - The operation over ten years of a simple and practical method of collaboration between general surgeons and geriatricians is described. This was designed, by means of a weekly ward round by geriatricians and consultant surgeons on general surgical wards (120 beds), to give geriatric medical advice and, when appropriate, to arrange transfer for geriatric assessment, medical treatment and rehabilitation, long-term care, or terminal care. Some 240 such transfers are described, comprising approximately 2% of all patients over the age of 65 admitted to the surgical units. The commonest single surgical diagnosis was of malignant disease. A total of 43% had had no operation and 18% had no medical diagnosis. 64% of those transferred for assessment etc. went home, half of them within two weeks, but nearly a third of them after more than four weeks. The system was effective, and benefited both surgeons and geriatricians, at no cost to the former and little to the latter in terms of time or increase in work load. PMID- 1517091 TI - Trends in hospital discharge rates for pelvic inflammatory disease in Scotland, 1975-1985. AB - This paper describes trends in hospitalisation for pelvic inflammatory disease in Scotland between 1975 and 1985. The age-standardised hospital discharge rate per 100,000 for all pelvic inflammatory disease in women aged 15-44 rose from 100.1 in 1975 to 143.8 in 1985. Rates of acute pelvic inflammatory disease increased by 58%, from 66.3/100,000 in 1975 to 104.5/100,000 in 1985, but the rate of discharge for chronic disease rose only slightly from 33.8/100,000 to 39.3/100,000. About one quarter of acute cases underwent surgery which enabled confirmation of the diagnosis, and there was no major change in this proportion between 1975 and 1985. The use of laparoscopy steadily increased, but this tended to replace other forms of surgery which could confirm the diagnosis. The percentage of chronic cases which were surgically confirmed increased steadily over the time period studied. A marked decrease in the mean duration of stay- from 9.2 days in 1975 to 4.9 days in 1985--meant that the total number of bed days used by patients with pelvic inflammatory disease fell by 16% between 1975 and 1985 despite the increase in the total number of cases. PMID- 1517092 TI - The Chief Scientist reports.... Problems in mounting and maintaining longitudinal studies--examples from dental health services research. AB - There already exists a body of literature on the conduct of classical epidemiological studies. However, guidelines tend towards detailing how such studies should be conducted and may not prepare the reader for the less-than perfect scenarios that will inevitably be encountered. The Dental Health Services Research Unit in Dundee has been involved in longitudinal studies of dental treatment and dental health since its inception in 1979. The problems encountered in this research are considered under the headings of mounting the studies, samples, data collection, external changes, internal changes, dissemination and curtailment. It is hoped that a description of the often unpredictable problems associated with a particular set of studies will provide an insight which may assist others embarking on analogous projects in health services research. PMID- 1517093 TI - Planning service for dementia. PMID- 1517094 TI - Theory in health education practice. AB - Although social and behavioral science theories are claimed to be able to contribute greatly to the effectiveness of health education programs, most practitioners in the profession seem to doubt this, and very few ever deliberately use theories in their work. Some reasons for such diverse views reside in the nature of the theories, in the very different roles they play in the worlds of theory-minded and practice-oriented health educators, respectively, in widespread unrealistic expectations of what theories can and cannot contribute to practice, and in lack of appropriate training in theories and their uses. Suggestions are offered to both practicing and academic health educators on ways to bridge the gap between the two camps, to render theories more useful to practitioners, and to train practitioners and health education students to appreciate the potentials of theories and to acquire skills needed to utilize such potentials. PMID- 1517095 TI - What's the use of theory? AB - The barriers to the use of theory in health education practice are addressed by exposing common misperceptions of the nature and usefulness of theory. First, the mystique of theory is addressed through a discussion of theory development and the roots of theory in everyday experience. Two characteristics of theory, generalizability across settings or situations and testability, are described and linked to benefits for practice. Second, a guide for practitioners in applying theory to each stage of the intervention process is provided. A case example illustrates how theory can guide practice as well as the benefits to be gained by applying theory to program development. Finally, the bases for common negative misperceptions of theory are identified and clarified, and the beneficial nature of theory reviewed. PMID- 1517096 TI - Practitioners' use of theory: examples from a workgroup. AB - There is a continuing discussion within the field of health education about the relationship between theory and practice. Much of this discussion, particularly that which appears in professional journals, has been developed by academicians and is prescriptive. That is, it identifies ways in which theory should be used by practitioners. The purpose of this article is to facilitate this ongoing discussion by providing descriptive information on how theory is used by a group of health educators who work for the same organization. This information is used as a springboard for discussion more generally about the nature of theory in health education. This article represents the thinking and experiences of a dozen health professionals, in reaction to the question. "How do you use theory in your practice?" The authors believe this information will be useful in helping theoreticians develop more useful theory and helping practitioners increase their understanding of the utility of good theory. The division between theory and practice in the field of health education represents a significant opportunity and challenge to the discipline if energy can be redirected from criticism of the other "camp" to effective collaboration and enhanced effectiveness of health education efforts. PMID- 1517097 TI - Self-regulation of health behavior: the "take PRIDE" program. AB - Social cognitive theory, in particular, the construct of self-regulation was the basis for developing an educational program for older adults with heart disease. This paper discusses the theoretical principles utilized and describes the program activities based on them. Data from an evaluation conducted with 246 older heart patients who took part in the education are used to illustrate how social cognitive theory constructs operated empirically. PMID- 1517098 TI - The integration of theory with practice: a 12-year case study. AB - Although the integration of health education theory with practice has always been taught, this linkage has not always occurred as a systematic part of program or theory development. This paper reflects the 12-year experience of one health education program which started from a base not soundly grounded in theory and moved to one tightly linked with theory. Throughout this process, outcome data were collected allowing for evaluations of both practice and theory. PMID- 1517099 TI - The uses of theory in health advocacy: policies and programs. AB - This paper illustrates the utility of theory for health educators who advocate for health promotion policies and programs. It describes how diffusion of innovation and other social science theories were employed by a statewide coalition called the Health Promotion and Education Council of Virginia in its effort to reduce premature and preventable death and disability in the state. To this end the Council sought legislative action to accelerate the diffusion of health promotion throughout the state. Discussing elements of diffusion theory such as working through opinion leaders, creating information-exchange relationships, and tailoring the attributes of the innovation to achieve its objectives, the paper reviews the process through which the Council became an effective advocate, and the strategies it devised to communicate the innovation of health promotion to legislators. The legislation that was generated by the work of the legislative study committee and future uses of theory are also discussed. PMID- 1517100 TI - Theory and the empowerment of health education practitioners. AB - Both the nature of theory and the way it is taught can overpower health education practitioners. As a consequence, myths which maintain theory and practice in separate realms may develop. This paper argues that to remedy this situation, practitioners must be helped to gain greater control of theory. Specific suggestions for accomplishing this goal are offered in a three-part prescription. First, concepts and teaching methods are introduced to dismantle myths about theory and to help practitioners understand its origins, nature, and functions. Second, health educators are encouraged to acknowledge limitations in theories currently guiding their practice. Third, they are shown ways they can exert leadership in developing theory to fill these gaps and build a more adequate knowledge base for confronting contemporary practice problems. Through this exercise of power, health educators will gain control over theory and expand the boundaries of practice, while also enhancing their professional status. PMID- 1517101 TI - The beta- and delta-thalassemia repository. PMID- 1517102 TI - A new variant, HB Muscat [alpha 2 beta (2)32(B14)Leu----Val] observed in association with HB S in an Arabian family. AB - The silent Hb Muscat with a Leu----Val replacement at position beta 32 was discovered by reversed phase high performance liquid chromatography in two members of an Arabian family from Oman; in one person Hb Muscat occurred with Hb S and in the other with Hb A. Hb Muscat is slightly unstable but its presence has no apparent adverse effect on the health of its carriers. Additional hemoglobin abnormalities observed in this family were a common alpha-thalassemia-2 (-3.7 kb) and Hb S. The beta S haplotypes in the heterozygous carriers and the two sickle cell anemia patients were #19 (Benin) and #20 (Bantu); the latter likely originated from an East African population. PMID- 1517103 TI - Hb Bab-Saadoun or alpha 2 beta (2)48(CD7)Leu----Pro, a mildly unstable variant found in an Arabian boy from Tunisia. AB - Hb Bab-Saadoun which has a Leu----Pro substitution at position 48 of the beta chain was detected in a young Arabian boy living in Tunisia. His parents did not have the variant which suggests that it occurred as a spontaneous mutation. The substitution is located in the interhelical CD segment; leucine at beta 48 is an invariable amino acid that may be important as part of a spacer sequence between the two helices and its replacement by proline may affect the stability of the hemoglobin molecule. Hb Bab-Saadoun is unstable in heat and isopropanol stability tests and its chain was best isolated by parachloromercuribenzoate precipitation. It appears unlikely that the presence of Hb Bab-Saadoun results in a hemolytic anemia. PMID- 1517104 TI - HB Prato [alpha 31(B12)Arg----Ser] in a Calabrian family. PMID- 1517105 TI - Erythrocytosis secondary to HB Bunbury [alpha 2 beta (2)94(FG1)Asp----Asn]. PMID- 1517106 TI - Anomalous results from a new hematology analyzer reveal hemoglobinopathies. PMID- 1517107 TI - A mutation of CDS 82/83 (-G) observed in a Yugoslavian family with a heterozygosity for beta-thalassemia. PMID- 1517108 TI - Two beta-thalassemia mutations in Japan: codon 121 (GAA----TAA) and IVS-I-130 (G- --C). PMID- 1517109 TI - Japanese beta-thalassemia [codon 90 (GAG----TAG)] has at least two origins. PMID- 1517110 TI - A novel frameshift mutation: deletion of C in codons 74/75 of the beta-globin gene causes beta zero-thalassemia in a Turkish patient. PMID- 1517111 TI - A beta-thalassemia mutation found in Korea. PMID- 1517112 TI - Mild Hb Constant Spring-Hb H disease with beta zero-thalassemia trait. PMID- 1517113 TI - Types of alpha-globin gene deficiencies in Chinese newborn babies in the Guangxi region, P. R. China. PMID- 1517114 TI - Hemoglobinopathies in Sardinia. PMID- 1517115 TI - Is there a connection between genomic changes and wide hybridization? AB - The structural organization of a set of highly repetitive DNA sequences (HRS) of barley (Hordeum vulgare) was studied by blot-hybridization in the genomes of seven Hordeum L. species and several Hordeum x Secale hybrids. The copy numbers of the sequences, and length and intensity of the hybridization fragments varied among barley species; so, this set appeared to be useful as molecular markers for barley species. Structural rearrangements of some HRS were observed in hybrids. It was noteworthy that the genomic changes in the hybrids partially coincided with those that take place during species divergence; so, chromosomal rearrangements are likely to proceed according to certain rules. The possibility of cryptic mobile elements participating in the genomic rearrangements under stress factors of the remote hybridization, is discussed, the primary structure of a Bam HI fragment (999 bp long) of Hordeum vulgare DNA being the example. PMID- 1517116 TI - [Oncogenes and their significance for head and neck cancers]. AB - During the past few decades medical science has accepted the concept that cancer is a fundamental disorder of cellular growth control. A disorder can originate in some cells through changes in genes (DNA level: gene amplification, mutation and rearrangement) or their expression (RNA and protein levels), and stimulates growth in contrast to surrounding cells. Over the last decade genes affected in the cancer cell have been identified as well as the nature of changes undergone. Only a few of the known oncogenes play a role in head and neck cancer. These are epidermal growth factor receptor, c-myc, the ras gene family, int-2, hst-1 and bcl-1. In some clinical disorders, such as childhood neuroblastoma and breast cancer, oncogenes have been shown to play an important role in tumor staging or as a prognostic parameter. The aim for future therapy is the effective application of oncogenes (or "gene therapy") in clinical practice. PMID- 1517117 TI - [Critical retrospective evaluation of the treatment of 400 patients with laryngeal cancer]. AB - This retrospective study deals with the outcome of 401 patients with laryngeal carcinoma who were treated between 1975 and 1986 either by operation alone or by operation and irradiation. The patients as a group, the concepts of treatment, and the course of disease as found retrospectively are described. T and N categories are compared with the respective pT and pN categories: T and pT categories corresponded in 83.3% of the cases while there was only a 67.4% correspondence between each N and pN category. The survival rates using the Kaplan-Meier estimation according to the localization and extension of laryngeal tumor, pN category and method of resection are discussed in detail. PMID- 1517118 TI - [Mucociliary activity of free transplanted respiratory epithelium]. AB - The function of free grafted respiratory epithelium was investigated in inbred rats. In nine of ten animals it could be shown that the respiratory epithelium not only regenerated as an epithelial surface lining but also regained mucociliary activity. The grafted epithelium was able to secrete mucus, which was equal in protein fragmentation to the secretion of normal nasal mucosa. The grafted respiratory epithelium showed normal ciliary function which could be demonstrated by recording the ciliary beat pattern present and by subsequent histological examination. Morphologically, a regular structure of ciliae (9 + 2) was found on the upper pole of the regenerated ciliated cells. PMID- 1517119 TI - [Combination of velopharyngoplasty and transposition flap of buccal mucosa for primary reconstruction of the soft palate]. AB - Reconstruction of the soft palate after tumor surgery can present a challenge in closing the defect created and achieving a sufficient functional result. We present a new technique for primary reconstruction after partial or total resections of the soft palate. The method is based on the combination of a cranially pedicled pharyngeal mucosa muscle flap with an oral mucosal transposition flap. If partial resection of the lateral pharyngeal wall is also required, the method can be combined with a masseter crossover flap. Our present experience has shown that the surgical technique used will result in an uncomplicated and rapid primary two-layer reconstruction of the soft palate with a comparatively low postoperative complication rate and satisfactory functional results in speaking and swallowing. PMID- 1517120 TI - [New indications for the rotating chair test for side localization and determination of central compensation in vestibular function disorder]. AB - The horizontal vestibulo-ocular reflex was studied in normals and 35 patients with an acute or compensated unilateral peripheral vestibular deficit (PVD) in order to determine the efficacy of different response measures obtained from a rotating chair test in localizing the deficit side and defining its central compensation. The profiles of chair velocity and the visual fixation period were chosen in such a way that the slow phase velocity profiles were comparable to those obtained during caloric tests. Mean slow phase eye velocity measured during the culmination period elicited by constant chair acceleration of 5 degrees/s2 over 40 s was significantly reduced for rotations towards the side of an acute or compensated PVD. Per-rotatory gain asymmetry (after correcting for spontaneous nystagmus) was not always specific for the side of the deficit and often not significantly different from normal values in the compensated stage of the deficit. In combination both parameters (SPV and gain asymmetry) were reliable indicators (sensitivity 88%) of the underlying pathology and correctly localized the deficit side during the compensated state. The decay of post rotatory SPV followed a more rapid time course than normal during acute and compensated stages of the deficit. It may be concluded from those results that the rotating chair test is a valuable indicator of the presence and side of a peripheral vestibular deficit even when it has been centrally compensated. PMID- 1517121 TI - [Bilateral Gradenigo syndrome--on the value of an integrated therapy concept including hyperbaric oxygenation and chronic destructive inflammation of the skull base]. AB - The case of a 30-year-old female with bilateral Gradenigo's syndrome is presented in order to detail commonly applied therapy. In particular, the importance of a comprehensive therapeutic approach is emphasized that includes such adjuvant therapeutic options as hyperbaric oxygenation and the administration of specific immunoglobulins. Indications, therapeutic benefits and limitations of treatment modalities are discussed in relationship to current concepts of therapy. PMID- 1517122 TI - [Rhabdomyoma of the mouth floor--a case report]. AB - We report a rare case of an adult rhabdomyoma of the floor of the mouth in a 52 year-old woman. To date only 25 cases of such tumors have been described in the oral cavity. In spite of its large size (approximately 10 x 8 x 6 cm), the tumor could be completely removed. Up to now, 20 months after the removal of tumor, no recurrences, have occurred. PMID- 1517124 TI - Additions to FDA's drug use policy expected. PMID- 1517123 TI - Wood's light for demonstrating dental calculus. PMID- 1517125 TI - The need for change in postgraduate education, faculty development, and recruitment in American and Canadian veterinary colleges. PMID- 1517126 TI - Comparative study of the knowledge, attitudes, and behaviors of large animal veterinarians, dairy farmers, and dairy processors in Michigan on bovine somatotropin. AB - A cross-sectional epidemiologic study was conducted to evaluate two objectives. The first was to determine the knowledge, attitudes, and behaviors of large animal (dairy) veterinarians, dairy farmers, and dairy processors in Michigan toward the use of bovine somatotropin (BST). The second was to compare and contrast the data from the large animal veterinarians, dairy farmers, and dairy processors according to the knowledge, attitude, and behavior variables. A written questionnaire was used as an instrument to collect data relating to the objectives. Three basic types of questions were asked of each group: (1) how much do you know about BST? (knowledge-based question), (2) how do you feel about BST? (attitude-based question), and (3) how would you use BST or use dairy products produced through BST biotechnology (behavior-based question)? PMID- 1517127 TI - Veterinarians all. PMID- 1517128 TI - Friction and fact in the marketing of pharmaceuticals and biologics. PMID- 1517129 TI - Comparison of recoveries from halothane vs isoflurane anesthesia in horses. AB - Recovery from isoflurane anesthesia was shorter, with no difference in quality, compared with halothane anesthesia in 2 groups of horses. In 1 group, 12 horses scheduled for elective arthroscopy were randomly assigned to receive halothane or isoflurane for maintenance of anesthesia during surgery. In the other group, 6 horses received anesthesia only, on 2 occasions, with halothane on 1 occasion, and isoflurane on the other. Difference in the quality of recovery was not seen between isoflurane and halothane anesthesia in either group. In the group that had surgery, recovery to sternal position was significantly shorter when isoflurane was used. In the group not treated surgically, recovery to sternal and standing positions was significantly shorter with isoflurane. PMID- 1517131 TI - Renal amyloidosis in a family of beagles. AB - Renal amyloidosis was confirmed in 6 related male and female Beagles, ranging in age from 5 to 11 years. The most commonly reported signs of illness included lethargy, anorexia, vomiting, and weight loss. Common clinicopathologic abnormalities were normocytic, normochromic anemia; hypoalbuminemia; azotemia; hypercholesterolemia; proteinuria; and urine specific gravity values below the normal range. Histologic examination of renal tissue from the 6 Beagles revealed moderate to severe glomerular amyloidosis with inconsistently observed mild medullary interstitial amyloidosis. Congo red-stained kidney sections from 4 of 4 affected dogs were potassium permanganate-sensitive, suggestive of reactive amyloidosis. Hereditary predisposition for renal amyloidosis was suspected in these Beagles. PMID- 1517130 TI - Use of zinc acetate to treat copper toxicosis in dogs. AB - Zinc acetate was used for the treatment and prophylaxis of hepatic copper toxicosis in 3 Bedlington Terriers and 3 West Highland White Terriers. Two dogs of each breed were treated for 2 years, and 1 of each breed for 1 year. A dosage of 200 mg of elemental zinc per day was required to achieve therapeutic objectives related to copper, which included a doubling of plasma zinc concentration to 200 micrograms/dl and a suppression of oral 64 copper absorption. The dosage was later reduced to 50 to 100 mg/day to avoid an excessive increase in plasma zinc concentration. The preliminary clinical results were good. Three dogs had mild to moderate active liver disease and high liver copper concentrations at the time of initiation of zinc administration. Biopsy of the liver 2 years later revealed a reduction in hepatitis and copper concentrations. One other dog without active hepatitis also had a reduction in hepatic copper concentrations over a 2-year period. All 6 dogs have done well clinically. On the basis of these findings, we believe zinc acetate to be an effective and nontoxic treatment for copper toxicosis in dogs. PMID- 1517132 TI - Frequency of reisolation of Staphylococcus aureus from multiple sequential milk samples. AB - Bacterial cultures were performed on multiple sequential composite samples of milk from 1,172 cows in 9 dairy herds. If the initial diagnosis of Staphylococcus aureus infection was based on the first positive culture, an average of 37.8% of subsequent cultures on the same cows were negative for S aureus. However, if the initial diagnosis of S aureus infection was confirmed by 2 or 2 of 3 sequential positive cultures and any conversions from S aureus positive to negative were confirmed by 2 or 2 of 3 sequential negative cultures, then only 17.0% converted to a negative diagnosis. Conversion of cows from S aureus culture-positive to negative varied between herds; 8.1 to 69% for single cultures and 0.0 to greater than 40% for confirmed cultures. PMID- 1517133 TI - Effects of vaccination against 18 immunogens in beef replacement heifers at weaning. AB - Humoral immune responses to vaccination, mean daily body-weight gains, morbidity, and mortality were compared in groups of beef replacement heifers from weaning to 4 months after weaning. The only difference in management among groups of heifers was the number and type of vaccines they received. Heifers were vaccinated at weaning (mean age, 205 days) and again 28 days later against 0, 1, 9, 10, 17, or 18 antigens, using commercially available monovalent and multivalent vaccines. The common vaccine component in all treatment groups was a modified-live bovine respiratory syncytial virus. Mean daily gain, morbidity, mortality, and serum neutralization antibody titers to bovine respiratory syncytial virus did not differ among treatment groups. Although the study revealed the safety of vaccinating beef heifers against 18 antigens at weaning, our data emphasized the need for serial vaccination to induce a measurable serum antibody response. PMID- 1517134 TI - Hypereosinophilia associated with transitional cell carcinoma in a cat. AB - A 14-year-old spayed female domestic shorthair cat was evaluated because of an abdominal mass and eosinophilia. Widely disseminated, transitional cell carcinoma of the urinary bladder was diagnosed histologically. To further characterize the eosinophilia, eosinophils were separated from other leukocytes and cultured in vitro. Harvested cells were evaluated for density and for in vitro survivability. Results of these tests, hyperplasia of bone marrow eosinophil precursors, and lack of tumor tissue eosinophilic infiltrates suggested that an eosinophilopoietic stimulus of undetermined origin was likely the cause of this cat's hypereosinophilia. PMID- 1517135 TI - Surgical repair of atresia jejuni in two calves. AB - Two Holstein calves with similar histories of not defecating since birth were determined to have atresia jejuni. Resection of the distended blind end of the jejunum and the remaining jejunum and ileum followed by a jejunocecostomy was performed. One calf died 7 months after surgery of unknown causes. The second calf has survived for greater than 1 year, and has maintained a growth rate similar to other calves its age. Atresia jejuni has been reported to be a universally fatal disorder of unknown pathogenesis. It has been postulated that intestinal atresia is caused by palpation of the amniotic vesicle at the time of pregnancy diagnosis, between days 36 and 42 of gestation. PMID- 1517136 TI - Chronic emesis caused by a nematode-induced gastric nodule in a cat. AB - A spirurid nematode-induced gastric nodule was believed to be responsible for chronic gastric irritation and vomiting in a domestic short-hair cat. Clinical improvement was noticed following surgical removal of the parasitic nodule in the wall of the pylorus. Morphologic characteristics of the parasite were most consistent with Spirocerca lupi. Infection with Spirocerca lupi is most commonly reported in Canids, often resulting in chronic granulomatous disease of the distal portion of the esophagus. In some animals, the lesions transform into fibrosarcomas and osteogenic sarcomas. PMID- 1517137 TI - Bronchial cartilage dysplasia with multifocal lobar bullous emphysema and lung torsions in a pup. AB - Bronchial cartilage dysplasia is believed to have caused lobar bullous emphysema in a 5-month-old Chow Chow that had exercise intolerance, progressive dyspnea, and episodic cough. Radiography of the thorax revealed hyperlucency of the left hemithorax, displacement of the mediastinum and heart to the right, and flattening of the diaphragm. The pup died shortly after the radiographs were obtained. Necropsy revealed massive hyperinflation with 180 degrees torsion of the cranial portion of the left cranial lung lobe, and hyperinflation with less than 180 degrees torsion of the right accessory lung lobe. Histologic examination of the affected lung lobes revealed a lack of bronchial cartilage, loss and displacement of alveolar walls, and bulla formation that resembled congenital (infantile) lobar emphysema of human beings. In this pup, lung lobe torsions may have been predisposed by bronchial cartilage dysplasia. PMID- 1517138 TI - Intestinal fibrosis with partial obstruction in five horses and two ponies. AB - Fibrosis of the small intestine led to recurrent colic and weight loss in 2 ponies and 5 horses. There was a reduction in the length of the small intestine to one-half normal in horses 4 to 7. Histologic examination revealed substantial small intestinal submucosal fibrosis and arteriole sclerosis. The cause was not determined, but an environmental factor was suspected because 3 horses were from the same farm and the other animals were from within a 10-mile radius of the farm. The submucosal fibrosis appeared to be secondary to sclerosis of arterioles in the submucosa and mesentery, with low blood flow state or altered vessel permeability. PMID- 1517139 TI - Clinical evaluation of axial pattern skin flaps in dogs and cats: 19 cases (1981 1990). AB - Nineteen axial pattern skin flaps were used in 16 dogs and cats to provide skin for repair of extensive cutaneous defects. Retrospective evaluation of medical records was used to determine percentage flap survival, postoperative complications, and long-term outcome of axial pattern skin flaps. The most common indication for use of axial pattern flaps was to augment wound closure following tumor resection (n = 7). Other indications included trauma (n = 5), chronic nonhealing wounds (n = 4), urine-induced cellulitis (n = 1), idiopathic dermal necrosis (n = 1), and chronic lymphoplasmocytic dermatitis (n = 1). Mean flap survival (+/- SD) was 96% (+/- 8). Postoperative complications included wound drainage (n = 15), partial dehiscence of the sutured flap (n = 7), distal flap necrosis (n = 6), infection (n = 3), edema (n = 3), and seroma formation (n = 2). After a median follow-up time of 5 months, evaluation of animals indicated that surgery provided successful wound reconstruction with good cosmetic results. Reconstruction of large cutaneous defects is facilitated by axial pattern flap application regardless of cause of wound. Postoperative complications are common but amenable to standard wound management techniques such as drain placement and surgical debridement of devitalized distal flap skin. PMID- 1517140 TI - Risk factors, clinical signs, and survival in cats with a clinical diagnosis of idiopathic hypertrophic cardiomyopathy: 74 cases (1985-1989). AB - Population characteristics, risk factors, and survival characteristics were evaluated in 74 cats with hypertrophic cardiomyopathy (HC) seen at North Carolina State University veterinary teaching hospital from 1985 to 1989, and compared with 82 clinically normal cats. The mean (+/- SD) age of cats with HC was 6.5 (4.0) years. Neutered males were at significantly greater risk (odds ratio 3.1) than neutered females. Breed, body weight, or coat color were not determined to be risk factors for HC. Tricolor cats were significantly underrepresented, probably reflecting the male predisposition for HC and not a true risk reduction associated with coat color. Forty-one cats were without clinical signs of heart disease (murmur and/or gallop sound only), 24 were in congestive heart failure, and 9 had systemic arterial embolism, 3 of which had concomitant congestive heart failure. The median survival time for 61 cats with HC, for which survival information could be obtained and that were not euthanatized on day 1, was 732 days. Survival was not affected by age at diagnosis, breed, body weight, or sex. However, clinical signs were important in determining prognosis; cats with heart rates greater than 200 beats/min survived significantly longer (median survival greater than 1,830 days) than those with heart rates greater than or equal to 200 beats/min (median survival = 152 days). Cats without clinical signs (median survival greater than 1,830 days) survived longer than those with clinical signs, and cats in heart failure survived a median of 92 days, compared with 61 days for those with systemic arterial embolism. Analysis of survival revealed no significant difference between the 2 groups of cats with clinical signs; however, all cats with embolism and only 60% of cats with heart failure were dead 6 months after diagnosis. PMID- 1517141 TI - Enteral feeding of dogs and cats: 51 cases (1989-1991). AB - Feeding commercial enteral diets to critically ill dogs and cats via nasogastric tubes was an appropriate means for providing nutritional support and was associated with few complications. Twenty-six cats and 25 dogs in the intensive care unit of our teaching hospital were evaluated for malnutrition and identified as candidates for nutritional support via nasogastric tube. Four commercial liquid formula diets and one protein supplement designed for use in human beings were fed to the dogs and cats. Outcome variables used to assess efficacy and safety of nutritional support were return to voluntary food intake, maintenance of body weight to within 10% of admission weight, and complications associated with feeding liquid diets. Sixty-three percent of animals experienced no complications with enteral feedings; resumption of food intake began for most animals (52%) while they were still in the hospital. Weight was maintained in 61% of the animals (16 of 26 cats and 15 of 25 dogs). Complications that did occur included vomiting, diarrhea, and inadvertent tube removal. Most problems were resolved by changing the diet or adhering to the recommended feeding protocol. Nutritional support as a component of therapy in small animals often is initiated late in the course of the disease when animals have not recovered as quickly as expected. If begun before the animal becomes nutrient depleted, enteral feeding may better support the animal and avoid serious complications. PMID- 1517142 TI - Radioimmunoassay monitoring of thyroid hormone concentrations in dogs on thyroid replacement therapy: 2,674 cases (1985-1987). AB - Serum iodothyronine concentrations from 4,064 samples submitted for monitoring of thyroid replacement therapy were evaluated in a retrospective study. After exclusion of samples because of the presence of 3,5,3' triiodothyronine (T3) autoantibodies, insufficient numbers of dogs on some commercial preparations or medication with corticosteroids or synthetic T3 preparations, data from 2,674 dogs remained. Data were analyzed by using information on dose, time after dosing, commercial product, and once-a-day or twice-a-day dosing regimens. Serum total thyroxine (T4) and total T3 and estimates of free T4 and free T3 were significantly high in serum from dogs given higher doses of synthetic L-thyroxine orally. Doubling the oral dosage did not double the serum iodothyronine concentrations, perhaps because of poor absorption or more rapid catabolism of the hormones at higher L-thyroxine doses. Wide variation in the therapeutic hormone concentrations was found. Some dogs given low dosages of L-thyroxine had normal iodothyronine concentrations whereas some others given higher dosages had low normal to low concentrations. Monitoring the serum concentrations is an objective way to ensure adequate concentrations for successful therapy. When a therapeutic trial is used as a diagnostic procedure, one should not rule out hypothyroidism unless a therapeutic monitoring sample has indicated that replacement dose and absorption of the exogenous iodothyronine has been adequate. Thyroid hormone concentrations peaked at 4 to 6 hours after oral administration of L-thyroxine for once-a-day and twice-a-day dosage regimens. Higher concentrations were achieved with once-a-day than with twice-a-day regimens at the same total daily dose.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1517143 TI - What is your diagnosis? Pyloric stenosis in a dog. PMID- 1517144 TI - Analbuminemic rats. PMID- 1517145 TI - Potentiation by tumor necrosis factor of mitoxantrone cytotoxicity to human ovarian cancer cell lines. AB - The cytotoxic activity of human recombinant tumor necrosis factor (rHuTNF) (from 0.01 to 10000 U/ml) was assayed on six human ovarian cancer cell lines and one human cervical carcinoma cell line using a crystal violet assay. rHuTNF was cytotoxic to four cell lines (A2780, A2774, SW626, PA1), while 3 cell lines (IGROV1, SKOV3, Me180) were marginally sensitive to its activity. However, under the same experimental conditions rHuTNF markedly enhanced the cytotoxicity of mitoxantrone, a chemotherapeutic drug targeted at DNA topoisomerase II, in six cell lines. The potentiation of mitoxantrone cytotoxicity was not caused by increased drug accumulation after rHuTNF treatment. No significant increase in cytotoxicity to Me180 cell line was seen when rHuTNF was added to mitoxantrone. PMID- 1517147 TI - Dose dependence of N-hydroxy-3,2'-dimethyl-4-aminobiphenyl-induced rat prostate carcinogenesis. AB - Groups of F344 rats were administered biweekly intraperitoneal injections of N hydroxy-3,2'-dimethyl-4-aminobiphenyl (N-OH-DMAB) at a dose of 5, 10 or 20 mg/kg body weight or DMAB, the parent compound, at a dose of 25 mg/kg body weight, for a total of 10 times. Prostate carcinomas in the ventral lobe developed in a N-OH DMAB dose-dependent manner (0, 17.6 and 66.7%, respectively) with limited tumor yields in other organs. Although intraperitoneal administration of DMAB was similarly found to induce prostate tumors, it also caused severe chemical peritonitis, which resulted in a high mortality. The present data confirmed that intraperitoneal administration of N-OH-DMAB provides a relatively specific induction method for models of prostate carcinogenesis. PMID- 1517146 TI - Promoting effects of potassium dibasic phosphate on early-stage renal carcinogenesis in unilaterally nephrectomized rats treated with N-ethyl-N hydroxyethylnitrosamine. AB - The effects of potassium dibasic phosphate (PDP), potassium aluminum sulfate (PAS) and copper sulfate (CS) on early-stage renal carcinogenesis were investigated in unilaterally nephrectomized male Wistar rats after N-ethyl-N hydroxyethylnitrosamine (EHEN) administration. After feeding 1,000 ppm EHEN, or basal diet for 2 weeks and removal of the left kidney at week 3, male Wistar rats were divided into 8 groups of 20 rats each. These groups received the following dietary treatments: 50,000 ppm PDP, 50,000 ppm PAS, 5,000 ppm CS or basal diet, respectively, for 18 weeks from weeks 3 to 20. The average numbers of adenomatous hyperplasias counted as preneoplastic lesions in the EHEN with 50,000 ppm PDP group were significantly higher than in the EHEN alone group or the EHEN followed by 50,000 ppm PAS or 5,000 ppm CS group. The treatment with 50,000 ppm PDP induced renal calcification and promoted the development of preneoplastic lesions in unilaterally nephrectomized rats treated with EHEN, but that with 50,000 ppm PAS or 5,000 ppm CS did not. PMID- 1517148 TI - Reversibility of carcinogen-induced rat forestomach basal cell hyperplasia is due to squamous cell differentiation. AB - The mechanisms of reversibility of basal cell hyperplasia in the rat forestomach were investigated. Male F344 rats were given an initial single gastric intubation of N-methyl-N'-nitro-N-nitorosoguanidine and then received 2% butylated hydroxyanisole in the diet from the third week to the 26th week. Rats were killed at weeks 26 and 46 after return to basal diet and their forestomachs were removed. Bromouracil deoxyriboside (BUdR) was administered as a single i.p. injection 1 h before death or by osmotic minipump (120 micrograms/h) continuously for 7 days before death. Additional animals were maintained for 2 or 4 weeks after removal of osmotic minipumps to allow assessment of the fate of proliferating populations. In each case BUdR-labeled cells were demonstrated by immunohistochemistry by immunohistochemistry. At week 26, hyperplastic changes were more pronounced than at week 46. Squamous cells above basal cell hyperplasias were strongly labeled even 4 weeks after cessation of continuous BUdR Three-dimensional reconstruction of persisting basal cell hyperplasias showed almost all basal cells limited to a thin sheet in direct contact with the squamous cell layer, occasional separate islands demonstrating differentiation to squamous cells and formation of epidermal cysts. The results thus showed that the mechanism of reversibility of basal cell hyperplasia involves differentiation of basal cells to squamous cells. PMID- 1517149 TI - A serine protease-inhibitory benzamidine derivative inhibits the growth of human colon carcinoma cells. AB - The inhibitory effect of a serine protease-inhibiting tetra-benzamidine derivative, TAPP-Br, on the cell growth of 8 human colon carcinoma cell lines was examined and the mechanism of the inhibition was analyzed. TAPP-Br inhibited the cell growth of all the colon carcinoma cell lines, and this effect was irreversible. The expression of mRNAs for nuclear oncogenes such as MYC, FOS and JUN was decreased by TAPP-Br after treatment for 3 h and the effect continued for 48 h. mRNA expression of epidermal growth factor receptor, transforming growth factor-beta and type IV collagenase was suppressed at 48 h after the initiation of TAPP-Br treatment, suggesting an indirect action of TAPP-Br. TAPP-Br decreased protein kinase C activity in the particulate fraction, whereas it increased the enzyme activity in the soluble fraction. These findings overall suggest that the serine protease inhibitor, TAPP-Br, might inhibit the cell growth of colon carcinoma cell lines through suppressing the expression of genes whose promoter contains a 12-O-tetradecanoylphorbol-13-acetate-responsive element or serum responsive element. PMID- 1517150 TI - Therapeutic effect of ansamitocin targeted to tumor by a bispecific monoclonal antibody. AB - We have constructed a murine hybrid hybridoma that secretes a bispecific monoclonal antibody (mAb) by fusing a hybridoma secreting an anti-ansamitocins mAb with a hybridoma secreting an anti-human transferrin receptor (TfR) mAb that binds to human A431 epidermoid carcinoma cells. The bispecific mAb, reactive to both ansamitocins and TfR, was purified by a combination of hydrophobic column chromatography and hydroxyapatite high-performance liquid chromatography, and evaluated in in vivo experiments using human tumor cell-implanted nude mice. Ansamitocin P-3 targeted through one of the antigen combining sites of the bispecific mAb was potentially more effective in suppressing the growth of established A431 tumor xenografts implanted on nude mice than unconjugated ansamitocin P-3 or the immunoconjugate of ansamitocin P-3 and monospecific anti ansamitocins antibody, and the targeted ansamitocin P-3 finally eradicated the tumor mass. The bispecific mAb also played an important role in reducing such undesirable side-effects of ansamitocin P-3 as the loss of body weight, the damage to liver functions and the decrease in the number of white blood cells. PMID- 1517151 TI - Antitumor effect of PSK at a distant site: tumor-specific immunity and combination with other chemotherapeutic agents. AB - The antitumor effect of PSK, a Coriolus preparation, was analyzed with the double grafted tumor system in which BALB/c mice received intradermal inoculations of syngeneic Meth-A fibrosarcoma in the right (primary tumor, 10(6) cells) and left (distant tumor, 2 x 10(5) cells) flanks. Intratumoral administration of PSK significantly inhibited the growth of not only the right but also the left tumor. PSK also inhibited the growth of a methylcholanthrene-induced fibrosarcoma BAMC 1, and a methylurethane-induced adenocarcinoma Colon 26 in the double grafted tumor system of syngeneic BALB/c mice. However, when the left distant tumor was different from the right Meth-A tumor, the intratumoral administration of PSK in the right tumor was unable to inhibit the growth of the left BAMC-1 or RL male-1 tumor. The PSK-induced immunity, therefore, is tumor-specific and T lymphocytes may play an important role in antitumor memory function. The enhancement of concomitant immunity by PSK treatment was completely impaired by previous intravenous administration of an alkylating agent, cyclophosphamide (CY). The enhancement of sinecomitant immunity by PSK treatment was also impaired by previous CY intravenous administration. The antitumor effect of PSK was suppressed by previous intravenous administration of another alkylating agent, ACNU. It is possible that alkylating agents suppress the function of effector T cells and granulocytes which are very important for the antitumor immune cascade reaction due to PSK treatment. On the other hand, the antitumor effect of PSK was enhanced by previous intravenous administration of an anti-metabolite, 5 fluorouracil. PMID- 1517152 TI - Protection of survival and hematopoiesis in irradiated mice by 5-fluorouracil. AB - The effects of whole-body irradiation on survival and the hematopoietic system were studied in mice treated with 5-fluorouracil (5-FU). Animals (ddY-SLC male mice, 8-10 weeks old) were injected with 5-FU (i.p.) as a single dose (150 mg/kg) at various times before or after irradiation with X-rays at graded doses (4.8 to 7.6 Gy). The treatment of mice with 5-FU 5 days before irradiation was the most effective for the reduction of radiation lethality, having a radioprotective effect. The dose reduction factor (DRF) was 1.24. However, treatment with 5-FU at 1 day and 2 hours before, or at various times after irradiation significantly increased the radiation lethality compared to the untreated controls, creating a radiosensitizing effect. The decrease or the increase of radiation lethality exhibited by 5-FU was similar to the radiation-dose relationship pattern shown by endogenous and exogenous CFU-S. The pattern of change of thrombocyte counts in the circulating blood after irradiation was greatly modified by pretreatment with 5-FU 5 days before irradiation, effectively lessening the radiation-induced depression. In contrast, the post-irradiation patterns of leukocyte and erythrocyte variation did not show any significant change due to pretreatment with 5-FU. PMID- 1517153 TI - Myeloprotective activity of deoxyspergualin: influence on splenic colony-forming cell injury and antitumor activity of mitomycin C in mice. AB - We have examined the efficacy of deoxyspergualin (DSG) in protecting splenic colony-forming cells (CFU-S) from mitomycin C (MMC)-induced damage. The main findings of the study are as follows. (1) When DSG was administered at doses of 1.5 and 3 mg/kg for 7 days before the MMC injection, the decrease of the femoral CFU-S caused by MMC was diminished on the day after the MMC injection. The optimal dose was found to be 3 mg/kg. (2) In animals receiving 3 mg/kg DSG for at least 3 days preceding the MMC injection, the femoral CFU-S was more than 200% of that in the MMC alone group one day after the MMC injection. (3) The number of femoral CFU-S in the mice which received 3 mg/kg DSG for 3 days prior to MMC was significantly restored day by day and reached 70% of normal at 5 days after the MMC injection, while it was only 13% of normal in the MMC alone group. Moreover, the prior DSG administration significantly diminished the MMC toxicity to circulating platelets. (4) DSG administration (3 mg/kg) 3 days prior to MMC did not weaken the antitumor activity against colon 26 adenocarcinoma or P388 leukemia when compared with MMC alone. These findings have shown the ability of DSG specifically to protect the animals against bone marrow toxicity caused by MMC without interfering with the antitumor activity. PMID- 1517154 TI - A novel type of phospholipase A2 inhibitor, thielocin A1 beta, and mechanism of action. AB - Thielocin A1 beta, a novel phospholipase A2 inhibitor, was isolated from Thielavia terricola RF-143. It inhibited various phospholipase A2s in a dose dependent manner. Among these, group II phospholipase A2 from rat was most sensitive to thielocin A1 beta (IC50 = 0.0033 microM). The inhibition of phospholipase A2 by thielocin A1 beta was independent of Ca2+ and substrate concentration. In addition, the inhibition of rat group II phospholipase A2 was noncompetitive (Ki = 0.0068 microM) and reversible. Furthermore, thielocin A1 beta quenched the relative fluorescent intensity of Naja naja venom phospholipase A2 and in a dose-dependent manner; 50% quench was noted with a molar ratio of thielocin A1 beta/enzyme of 2.2. These observations indicated that inhibition of phospholipase A2 by thielocin A1 beta may result from direct interaction with the enzyme. PMID- 1517156 TI - TA-3037A, a new inhibitor of glutathione S-transferase, produced by actinomycetes. I. Production, isolation, physico-chemical properties and biological activities. AB - TA-3037A, a new inhibitor of glutathione S-transferase was discovered in the fermentation broth of Streptomyces sp. TA-3037. It was purified by chromatography followed by solvent extraction and then isolated as yellow needles. TA-3037A has the molecular formula of C16H11NO4. It was competitive with the substrate, and the inhibition constant (Ki) was 4.9 microM. PMID- 1517155 TI - Isolation, characterization and biological activities of concanamycins as inhibitors of lysosomal acidification. AB - Four new analogues of concanamycin family, designated concanamycins D, E, F G, were isolated from the mycelium of Streptomyces sp. A1509 by solvent extraction, silica gel column chromatography and HPLC. Structures of these compounds were identified by the combination of spectroscopic analyses. All of these compounds were structurally related to concanamycins A, B and C, which had been isolated previously, and inhibited the acidification of rat liver lysosomes at 10(-11)-10( 9) M concentration. The structure-activity study showed that the 18-membered macrolide ring and the 6-membered hemiketal ring portions of the molecules of concanamycin family are responsible for potent inhibitory activity. PMID- 1517157 TI - TA-3037A, a new inhibitor of glutathione S-transferase, produced by actinomycetes. II. Structure determination. AB - TA-3037A, a new inhibitor of glutathione S-transferase, has been isolated from the culture broth of Streptomyces sp. TA-3037. The structure of TA-3037A was defined as (Z)-3-benzylidene-3,4-dihydro-2-oxo-2H-1,4-benzoxazine-5-carboxylic acid by an analysis of spectral properties and chemical studies of TA-3037A and its derivatives. PMID- 1517158 TI - Tirandalydigin, a novel tetramic acid of the tirandamycin-streptolydigin type. I. Taxonomy of the producing organism, fermentation and biological activity. AB - Tirandalydigin is a new tetramic acid antibiotic which was discovered in a screen designed to find compounds with activity against pathogenic anaerobic bacteria. It was named tirandalydigin because it possesses structural features that are common to both tirandamycin and streptolydigin. The producing culture, strain AB 1006A-9, is a Streptomyces and was compared to the streptomycetes that synthesize tirandamycin and streptolydigin. It is closely related to the former culture and was named Streptomyces tirandis subsp. umidus. Tirandalydigin has MICs in the range of 0.5 to 32 micrograms/ml against many pathogenic anaerobes, streptococci, enterococci and legionellae. PMID- 1517159 TI - Studies on viridenomycin, a novel 24-membered macrocyclic polyene lactam antibiotic. AB - A new antitumor antibiotic, designated AL081, was obtained from the culture filtrate of an actinomycete identified as Streptomyces gannmycicus, and found to be identical with viridenomycin by direct comparison. The structure of the antibiotic was determined by NMR spectral analysis including a variety of two dimensional techniques to be a novel 24-membered macrocyclic polyene lactam. Viridenomycin prolonged the survival periods of mice bearing P388 leukemia and B16 melanoma cells. PMID- 1517160 TI - Synthesis and biological activities of cyclopropenone antibiotic penitricin and congeners. AB - A number of derivatives of the cyclopropenone antibiotic penitricin have been synthesized by the reaction of metalated cyclopropenone acetals with electrophiles. Studies on the antimicrobial structure-activity relationships indicated that the penitricin skeleton, hydroxymethylcyclopropenone, is indispensable for antimicrobial activity. These compounds were also found to display cytotoxic activity. PMID- 1517161 TI - Isolation and characterization of furanomycin nonproducing Streptomyces threomyceticus mutants. AB - Stable mutants that are blocked in the production of the polyketide antibiotic furanomycin were generated by treatment of Streptomyces threomyceticus (ATCC 15795) with a combination of N-methyl-N'-nitro-N-nitrosoguanidine (NTG) and ultraviolet light. On the basis of their cosynthetic properties in mixed culture, the mutants were grouped into eleven phenotypic classes. The polarity of the cosynthetic reactions for seven classes of mutants was revealed by filtrate feeding experiments. This allowed them to be arranged in the most probable linear sequence of metabolic blocks. One of the remaining groups of mutants exhibited no cosynthetic behavior and is believed to be blocked in a gene that regulates furanomycin biosynthesis. PMID- 1517162 TI - Cloning and analysis of a gene (sms13) encoding sannamycin B-glycyltransferase from Streptomyces sannanensis and its distribution among actinomycetes. AB - A gene encoding sannamycin B-glycyltransferase (sms13) of Streptomyces sannanensis IFO 14239 was identified by cloning and complementation of S. sannanensis mutant SN13 which is blocked at the interconversion of sannamycins B and A. The cloned DNA fragment also permitted the conversion of fortimicin B to A both in S. sannanensis SN13 and Streptomyces lividans TK23. DNA sequences similar to sms13 were detected in all five producers of the fortimicin-group antibiotics, Micromonospora olivasterospora ATCC 21819 (fortimicin-producer), Micromonospora sp. strain SF-2098 ATCC 31580 (SF-2052), Dactylosporangium matsuzakiense ATCC 31570 (dactimicin), Streptomyces tenjimariensis ATCC 31603 (istamycin), and Saccharopolyspora hirsuta ATCC 20501 (sporaricin). This suggests that these genes of similar function from different genera were derived from a common ancestral gene. PMID- 1517163 TI - Secondary metabolites by chemical screening. 20. Decarestrictines, a new family of inhibitors of cholesterol biosynthesis from Penicillium: III. Decarestrictines E to M. PMID- 1517164 TI - Isolation and identification of new anthracycline antibiotics, rubomycins F and H. PMID- 1517165 TI - The structure of CP-96,797, a polyether antibiotic related to K-41A and produced by Streptomyces sp. PMID- 1517166 TI - The structure of tetracenomycin C. PMID- 1517167 TI - Synthesis and antibacterial activity of 7-[2-(2-aminooxazol-4-yl)-(Z)-2 alkoxyiminoacetamido]-cephalosporin antibiotics. PMID- 1517168 TI - Emerging food-borne pathogens and their significance in chilled foods. PMID- 1517169 TI - A study of the incidence of different fluorescent Pseudomonas species and biovars in the microflora of fresh and spoiled meat and fish, raw milk, cheese, soil and water. AB - Of 182 various foodstuffs and environmental samples examined, 86% had microflora containing fluorescent Pseudomonas in differing proportions. A computer-aided technique was used to identify most of the 445 fluorescent strains. Pseudomonas fluorescens biovar V-1 was most frequently isolated (24%); it either predominated or was present in all types of samples. Other strains, belonging to the other subgroups of biovar V (V-2, V-4, V-5, V-6 and V-7), together represented 14.3%. We also identified Ps. fluorescens biovars I-1 and I-2 (13.9%), II-1 and II-3 (3.6%), III-1 and III-2 (8.7%), IV-2 (0.7%); Ps. putida A and B (11%); Ps. lundensis (10.3%); group B3 (2%) and Ps. aeruginosa (0.7%). Unidentified strains accounted for 10.6% of the flora, many resembling Ps. fluorescens biovar V. Although the presence of Ps. fluorescens V-1 was often marked, other taxa predominated or were present in large quantities in some particular samples, such as Ps. fluorescens I-1 in raw milk and cheese, Ps. lundensis in spoiled meat and Ps. fluorescens III-1 in spoiled fish. Pseudomonas putida A and B were evident in environmental rather than in food samples. PMID- 1517170 TI - Nucleotide sequence and structural relationships of a chloramphenicol acetyltransferase encoded by the plasmid pSCS6 from Staphylococcus aureus. AB - The 4.6 kb chloramphenicol resistance (Cm) plasmid, pSCS6, isolated from a naturally occurring Staphylococcus aureus biotype C encoded an inducible chloramphenicol acetyltransferase (CAT). The respective cat gene and its regulatory region were cloned. Sequence analyses revealed two open reading frames: one for a 9-amino acid leader peptide and the other for the 215-amino acid CAT monomer. Comparisons of the predicted CAT amino acid sequences revealed a high degree of similarity between CAT from pSCS6 and the CAT variants encoded by Cm plasmids of the pC221 family. These close structural relationships suggested an intraspecific exchange of Cm-determinants between Staph. aureus of human and bovine biotype. PMID- 1517171 TI - Diagnostic application of monoclonal antibodies to outer membrane protein for rapid detection of Salmonella. AB - Monoclonal antibodies produced to Salmonella enteritidis outer membrane proteins were screened against 57 Salmonella serovars and several related enterobacteria. Those detecting all Salmonella serovars and none of the related enterobacteria were used in a microtitre plate antigen capture ELISA to screen clinical samples. Sixty-one of 2100 samples yielded salmonellas after incubation for 24 h in selective media by conventional culture. Of these 58 were detected by the ELISA. Sixty-five false positives by ELISA were found to be Enterobacter spp. The results show the potential of this ELISA to eliminate a large proportion of the salmonella-negative cultures at an early stage. PMID- 1517172 TI - Multiple typing techniques applied to a Clostridium perfringens food poisoning outbreak. AB - Twenty-one stool specimens obtained from persons implicated in two food poisoning outbreaks at the same institution in Smith Falls, Ontario, were examined for Clostridium perfringens. Ninety-two colonies of Cl. perfringens (3-5 per stool specimen) were typed with antisera, bacteriocins and by plasmid analysis. They were also tested for the in vitro production of bacteriocin and enterotoxin. Sixteen of the 21 stool specimens were tested directly for enterotoxin. This was detected in 13, five of which were from individuals listed as 'asymptomatic' food handlers. The predominant strain isolated from 15 of the 21 stool samples produced bacteriocin and enterotoxin in vitro, contained no plasmids, and was of a common bacteriocin type and serotype. PMID- 1517173 TI - Effect of culture age, pre-incubation at low temperature and pH on the thermal resistance of Aeromonas hydrophila. AB - The thermal resistance of Aeromonas hydrophila strain NCTC 8049 was determined within the range 48 degrees-65 degrees C with a thermoresistometer TR-SC and McIlvaine buffer. The effects of culture age, pre-incubation at 7 degrees C and the pH of the heating menstruum were evaluated. The pattern of thermal death was dependent on culture age. Cells heated in the late logarithmic growth phase (15 h at 30 degrees C) were twice as resistant as those in the early stage (5 h at 30 degrees C), and the maximum D-value was obtained after 72 h incubation (5.5 total increase). The age of the cells did not affect z-values significantly. The heat resistance of cells incubated for 48 h at 30 degrees C increased (twice) after holding at 7 degrees C for 72 h. Pre-incubation at low temperature of older cultures (72 h, 30 degrees C) did not influence their D-values. Maximum heat resistance was found at pH 6.0 and minimal at pH 4.0. Decreasing the pH from 6.0 to 4.0 reduced D-values by a factor of 5. Although the strain studied was heat sensitive (D55 degrees C = 0.17 min; z = 5.11 degrees C), survivor curves of cultures older than 50 h showed a significant tailing. Organisms surviving in the tails were only slightly more resistant than were the original population. PMID- 1517174 TI - Factors affecting antibacterial activity of hop compounds and their derivatives. AB - The antibacterial effect of weak acids derived from the hop plant (Humulus lupulus L.) increased with decreasing pH. Analysis of the minimum inhibitory concentration of such compounds against Lactobacillus brevis IFO 3960 over pH 4-7 suggests that undissociated molecules were mainly responsible for inhibition of bacterial growth. The antibacterial activity of trans-isohumulone was ca 20 times greater than that of humulone, 11 times greater than that of colupulone and nine times greater than that of trans-humulinic acid when the degree of ionization was taken into account. Monovalent cations (K+, Na+, NH4+, Rb+, Li+) stimulated antibacterial activity of trans-isohumulone but the effect was smaller than that observed with H+. The response to divalent cations varied: Ca2+ had little effect on antibacterial activity, whereas Mg2+ reduced activity. Lipid materials and beta-cyclodextrin also antagonized the antibacterial action of trans-isohumulone. PMID- 1517175 TI - Effects of chlorhexidine diacetate on Candida albicans, C. glabrata and Saccharomyces cerevisiae. AB - The effects of chlorhexidine diacetate (CHA) on Candida albicans, C. glabrata and wild-type and mannan, and permeability mutants of Saccharomyces cerevisiae have been studied. A CHA concentration of 10 micrograms/ml had little lethal activity against the Candida strains, but was more effective against S. cerevisiae. Concentrations of 100 and especially 1000 micrograms/ml brought about a much more rapid death of cells. 2-Mercaptoethanol enhanced the activity of CHA to some extent. Some of the mutant strains of S. cerevisiae were rather more sensitive than the wild-type strain. The age of cultures of C. albicans and C. glabrata influenced their response to CHA. PMID- 1517176 TI - Numerical classification and identification of Aeromonas genospecies. AB - A total of 176 Aeromonas strains representing all currently characterized genospecies were tested for 329 biochemical characters. Overall similarities of all strains were determined by numerical taxonomic techniques, the UPGMA algorithm and the SSM and the SJ coefficients as measures of similarity. Sixteen clusters (two or more strains) and seven unclustered strains were recovered at the 93.5% similarity level (SSM). Genospecies 1, 4, 5, 6, 7, 9, 12 and 13 were largely represented by single phena, whereas strains of genospecies 2 and 3 were found in closely-related phena. Strains belonging to genospecies 8 formed two distinct biotypes. Strains belonging to genospecies 11 formed a subcluster within a cluster representing different genospecies. In general, similar groupings were obtained with the Jaccard coefficient at a similarity level of 80.0% (SJ) with minor changes in the definition of clusters. The phenetic data showed good correlation with the taxa defined by DNA/DNA hybridization and those obtained by multilocus enzyme analysis. For all genospecies (independent from cluster assignment) 30 diagnostic characters were selected to construct a matrix for probabilistic identification. The correct identification rate of the matrix was 71.51% taking a Willcox probability greater than 0.99, and 83.7% taking a Willcox probability greater than 0.9 as identification threshold levels. PMID- 1517177 TI - Evaluation of coliforms as indicators of water quality in India. AB - The total and thermotolerant coliform counts in rural drinking water derived from ground water, piped supplies and surface water are reported for a number of areas in India. To evaluate these counts as indicators of recent faecal contamination the total coliforms and thermotolerant coliforms isolated have been identified. Thermotolerant Escherichia coli formed 11.7% of the total coliforms and 75.1% of the thermotolerant coliforms. Citrobacter sp. (20.4%) and Klebsiella sp. (50.9%) were the other common total coliforms isolated and, among the thermotolerant coliforms, Klebsiella sp. (16.4%) was the only other organism frequently encountered. The total coliform counts were significantly correlated with water temperature. The applicability in tropical areas of standards developed for temperate climates is discussed. PMID- 1517178 TI - An early case of the Zollinger-Ellison syndrome produced by a carcinoid tumor of the duodenum. AB - We have reported a case of Zollinger-Ellison Syndrome which proved to be due to a small carcinoid tumor of the wall of the duodenum. At the time that this was found, I could not find any such cases in the literature. In talking with Dr. Ellison personally, it was my impression that he was probably not aware of this syndrome. There are relatively few cases in the literature, and in a report by Dr. Van Heerden, et al from the Mayo Clinic, of 154 patients with carcinoid tumors of the GI tract, there were only two cases of the carcinoid tumor found the duodenum. One had a gastrin producing tumor 1 cm in diameter with positive nodes which was excised locally, and the patient was alive and well and not taking medication after 10 years. In this case, I think that serendipity played a great part, because I had no knowledge of the relation between the carcinoid tumor and the severe ulcer diathesis it produced. PMID- 1517179 TI - St. Louis encephalitis in Arkansas. AB - The first outbreak of St. Louis encephalitis (SLE) in Arkansas occurred in Pine Bluff (Jefferson County) during July-August 1991. Cases of SLE were identified mainly through reporting by physicians in Jefferson and surrounding counties. In addition, testing of stored cerebrospinal fluid specimens, a hospital chart review, and a serosurvey were performed in Pine Bluff. Twenty-eight Arkansas residents, five of whom died, had cases of SLE. Half the case patients were over age 60, and nearly half had hypertension. The serosurvey confirmed that infection with the SLE virus was not new to Pine Bluff, and that most infections in 1991 were asymptomatic. Arkansas physicians may see more cases of SLE in 1992. SLE epidemiology, clinical presentation, diagnosis, and preventive measures are reviewed. PMID- 1517180 TI - Treatment of cervical dystonia (torticollis) in adults with botulinum A toxin. AB - Dystonias can be classified by etiology (idiopathic or symptomatic), by age of onset (childhood, adolescence or adult), and by anatomical involvement (focal, segmental or generalized). Cervical dystonia (torticollis) is one of the most common focal dystonias. We describe our experience in the treatment of 15 consecutive cervical dystonia patients by chemodenervation with botulinum A toxin (BOTOX), with significant improvement being objectively measured. Botox is accepted as a safe and efficacious modality for the treatment of cervical dystonia. PMID- 1517181 TI - Taxes on cigarettes are low in Arkansas. PMID- 1517182 TI - CHAR succeeds in petition goal. PMID- 1517183 TI - In a heartbeat. Interview by David E. Reiser. PMID- 1517184 TI - Radiological case of the month. Thymoma. PMID- 1517185 TI - Method of making negative x-ray prints for reproduction. PMID- 1517186 TI - Copyright--some ethical considerations. PMID- 1517187 TI - Photomicrography--a brief history. PMID- 1517188 TI - How's your photo/illustration service? Do you really want to know? ... and what can you do to improve it? PMID- 1517189 TI - The use of animated drawings in medical motion pictures. PMID- 1517190 TI - Production of a dark field motion photomicrograph exhibiting flagella in motile bacteria. PMID- 1517191 TI - Clinical characteristics of trichotillomania and its response to fluoxetine. AB - BACKGROUND: In general, effective treatments for trichotillomania have been elusive. Although behavioral therapies and hypnosis have provided benefits to some, adult patients with chronic hair pulling have often proved refractory to treatment. Medication has generally been unhelpful until the recent introduction of serotonin reuptake inhibitors for the treatment of this condition. Furthermore, there has been little systematic study of the clinical characteristics of these patients. METHOD: Twenty individuals with trichotillomania were interviewed and were characterized on the basis of hair pulling patterns, comorbidity, obsessionality, and the presence of symptoms of depression and anxiety. Twelve patients participated in an open 16-week trial of fluoxetine (up to 80 mg/day). RESULTS: Compared with baseline scores derived from a scale of trichotillomania severity, severity scores at endpoint decreased (improved) by 34% (p less than .025). Among the 8 responders, the mean decrease in severity scores was 60%. Fifty-five percent (11 of 20) had current or past additional DSM-III-R Axis I diagnoses (disorders of mood, anxiety, and psychoactive substance use). CONCLUSION: We conclude that in an open 16-week trial, patients treated with fluoxetine improved significantly. Data are presented on comorbid conditions, depressive symptoms, and anxiety. Baseline behavioral assessments of patients with trichotillomania suggest that substantial differences exist between this syndrome and obsessive compulsive disorder. PMID- 1517192 TI - A preliminary investigation of the lifetime prevalence of anorexia and bulimia nervosa in patients with obsessive compulsive disorder. AB - BACKGROUND: Obsessive compulsive disorder (OCD) is currently classified as an anxiety disorder although it possesses many characteristics that distinguish it from other anxiety disorders. Clinically and neurobiologically, OCD appears to overlap somewhat with the eating disorders. METHOD: To assess in a controlled fashion the lifetime prevalence of the eating disorders in patients with OCD, we administered portions of the Structured Clinical Interview for DSM-III-R, Patient Version (SCID-P), to 62 patients (31 men, 31 women) with a primary DSM-III-R diagnosis of OCD. RESULTS: Among the OCD patients, the lifetime prevalence of anorexia nervosa and/or bulimia nervosa was 12.9% (N = 8), and an additional 17.7% (N = 11) met subthreshold criteria for either anorexia or bulimia nervosa. Interestingly, unlike multiple epidemiologic studies that have reported a substantial female preponderance among patients diagnosed with anorexia or bulimia nervosa, there was no significant gender difference in the lifetime prevalence of eating disorders among the patients with OCD. Almost 13% (N = 4) of the men and 6.5% (N = 2) of the women with OCD met criteria for a lifetime diagnosis of anorexia nervosa and 3.2% (N = 1) of the men and 6.5% (N = 2) of the women with OCD met criteria at some time in their lives for bulimia nervosa. In addition, subthreshold criteria for anorexia nervosa or bulimia nervosa were met by an additional 12.9% (N = 4) of the men and 22.6% (N = 7) of the women. CONCLUSION: These data suggest that OCD patients, regardless of gender, have a substantial lifetime prevalence of anorexia and/or bulimia nervosa. PMID- 1517193 TI - Factitious disorders with psychological symptoms. AB - BACKGROUND: Factitious disorders with psychological symptoms have been underdiagnosed and hence undertreated. Historically, the literature has focused on factitious disorder with physical symptoms, particularly Munchausen's syndrome. METHOD: The authors report three cases of factitious disorder with psychological symptoms that had diverse clinical presentations. RESULTS: Two of the patients had features of a psychiatric Munchausen's syndrome--being middle aged, aggressive men who falsified their symptoms, treatments, and backgrounds. The third patient was a younger woman with comorbid substance abuse, dysthymia, and borderline personality disorder. CONCLUSION: The authors feel that there is a need for refinement of diagnostic criteria, greater awareness, and evaluation of treatment approaches for this condition. PMID- 1517194 TI - Sensory phenomena associated with Gilles de la Tourette's syndrome. AB - BACKGROUND: Our study was conducted to characterize sensory phenomena experienced by Gilles de la Tourette's syndrome (TS) sufferers. Specific foci of the study were premonitory urges associated with motor and phonic tics, site sensitization, and disinhibition behaviors. METHOD: Twenty-eight subjects were recruited for participation in the study from the Tourette's Syndrome Association and from neurologists' patient lists. All had been diagnosed as having TS at least 2 years prior to the study. Patients were contacted by telephone and questioned in an attempt to screen for participants who experienced some sensory phenomena preceding or accompanying their tics. Interviews were conducted in person with 27 of the participants and by telephone with 1 participant. RESULTS: Twenty-two (82%) of the 28 subjects experienced premonitory urges prior to motor and vocal tics. Of these 22, 13 (57%) found the premonitory urges more bothersome than the tics themselves, and 12 (55%) thought the premonitory urges enhanced their ability to suppress tics. Of 20 subjects questioned about site sensitization, 14 (70%) had heightened sensitivity to tactile, auditory, and/or visual stimuli. Disinhibition-complex behaviors the subject knows are dangerous or inappropriate but feels incapable of refraining from--was found in 10 (36%) of the 28 subjects and occurred only in subjects experiencing premonitory urges. Premonitory urges and site sensitivity can occur alone or together. Several excellent narrative descriptions of sensory phenomena associated with TS were also obtained. CONCLUSION: Much information was gained that adds to the ongoing attempt to characterize sensory phenomena associated with TS. The sensory phenomena must be understood by clinicians who treat TS sufferers, as this study shows that they add significantly to the impairment caused by TS. PMID- 1517195 TI - Acute dystonia and fluoxetine. PMID- 1517196 TI - Usefulness of screening EEGs in psychiatric inpatients. PMID- 1517197 TI - Parnate formulation change. PMID- 1517198 TI - Clozapine-induced myoclonic jerks and drop attacks. PMID- 1517199 TI - Paraphilias, nonparaphilic sexual addictions, and social phobia. PMID- 1517200 TI - Expression of a mouse brain cDNA encoding novel gamma-aminobutyric acid transporter. AB - A nipecotic acid-resistant gamma-aminobutyric acid (GABA) transporter was cloned from a mouse brain cDNA library. The 2.3-kilobase cDNA clone contains an open reading frame of 1842 nucleotides encoding a protein of 614 amino acids. The predicted amino acid sequence indicates it is a member of the gene family of the sodium-dependent neurotransmitter transporters. The new GABA transporter, named GAT2, is highly homologous to the betaine transporter (BGT1) cloned from canine kidney. However, GAT2 expression in the brain distinguished it from BGT1 which was exclusively expressed in the kidney. The transcripts of GAT2 were found in the cerebral cortex, cerebellum, and brainstem as well as in kidney. Expression of GAT2 in Xenopus oocytes revealed a Km of 79 microM for GABA uptake which is about 10-fold higher than that of the high affinity GABA transporter (GAT1). The pharmacology of GAT2 is different from that of GAT1 because of lack of inhibition by guvacine and nipecotic acid and sensitivity to high concentrations of betaine and beta-alanine. GAT2 transports betaine with a Km of about 200 microM, but no significant transport of beta-alanine could be detected. The presence of mRNA encoding GAT2 in parts of the brain suggests it is a neurotransmitter transporter. PMID- 1517201 TI - The carboxyl-terminal extension of the D1 protein of photosystem II is not required for optimal photosynthetic performance under CO2- and light-saturated growth conditions. AB - Synthesis of the photosystem II D1 protein as a precursor with a carboxyl terminal extension occurs in almost all eukaryotic photosynthetic organisms examined so far, as well as in cyanobacteria. Processing of the D1 precursor has been recently postulated to play a regulatory role in the light-dependent migration of photosystem II units from the unstacked to the stacked thylakoids (Bowyer, J. M., Packer, J. C. L., McCormack, B. A., Whitelegge, J. P., Robinson, C., and Taylor, M. A. (1992) J. Biol. Chem. 267, 5424-5433). To test this hypothesis, site-directed mutagenesis and chloroplast transformation have been used to create a "preprocessed" mutant Chlamydomonas strain which synthesizes mature D1 protein directly. We have found that this strain is indistinguishable from wild type in terms of photosynthetic performance and cell doubling time under CO2- and light-saturated photoautotrophic growth conditions. PMID- 1517202 TI - Site-directed mutagenesis of GLUT1 in helix 7 residue 282 results in perturbation of exofacial ligand binding. AB - The structure-function relationship of the HepG2/erythrocyte-type glucose transporter (GLUT1) has been studied by in vitro site-directed mutagenesis. Chinese hamster ovary clones in which glucose transporters were transfected were shown by Western blotting with a GLUT1 anti-COOH-terminal peptide antibody to have expression levels of Gln282----Leu, Asn288----Ile, and Asn317----Ile mutations that were comparable with the wild type. All three mutant GLUT1 clones had high 2-deoxy-D-glucose transport activity compared with a nontransfected clone, suggesting that these residues are not absolutely required for the transport function. We have examined the possibility that the inner and outer portions of the transport pathway are structurally separate by measuring the interaction of the mutant transporters with the inside site-specific ligand cytochalasin B and the outside site-specific ligand 2-N-4-(1-azi-2,2,2 trifluoroethyl)benzoyl-1,3-bis(D-mannos-4 -yloxy)-2- propylamine (ATB-BMPA). All three mutant GLUT1 clones showed high levels of cytochalasin B labeling, and the N288I and N317I mutants showed high levels of ATB-BMPA labeling. In contrast to the transport and cytochalasin B labeling results, the transmembrane helix 7 Gln282----Leu mutant was labeled by ATB-BMPA to a level that was only 5% of the level observed in the wild type. We have confirmed that this mutant was defective in the outer site by comparing the inhibition of wild-type and mutant 2-deoxy-D glucose transport by the outside site-specific ligand 4,6-O-ethylidene-D-glucose. 4,6-O-Ethylidene-D-glucose inhibited wild-type transport with a Ki of approximately 12 mM, but this was increased to greater than 120 mM in the Gln282- --Leu mutant. Thus, of the 3 residues mutated in this study, only glutamine 282 substitution causes a major perturbation in function, and this is a specific and striking reduction in the affinity for the outside site-specific ligands ATB-BMPA and 4,6-O-ethylidene-D-glucose. PMID- 1517203 TI - Isolation and structural determination of a novel TRH-like tripeptide, pyroGlu Tyr-Pro amide, from alfalfa. AB - The tripeptide pyroGlu-Tyr-Pro amide was isolated from an aqueous extract prepared from dried alfalfa pellets. The tripeptide was quantitated using a competitive radioimmunoassay in which 125I-labeled thyrotropin-releasing hormone (TRH), is displaced from antibody specific to TRH (pyroGlu-His-Pro amide). The pyroGlu-Tyr-Pro amide was purified by passing the filtered extract through QAE Sephadex A25 at pH 5, followed by open bed chromatography on C18 silica using an H2O/methanol gradient, then preparative high performance liquid chromatography (HPLC) on microbondapak C18 using a 10 mM HCl/methanol gradient, followed by G-10 Sephadex chromatography, SP-C25-Sephadex chromatography, QAE-Sephadex chromatography at pH 10.1, analytical HPLC on a microbondapak C18 column eluted with 10 mm HCl/acetonitrile, and analytical HPLC reverse phase chromatography on an APEX phenyl column eluted with H2O/acetonitrile. The tripeptide was essentially homogeneous after the final chromatography step, as judged by correspondence of immunoreactivity with A280. The sequence of the alfalfa tripeptide was determined to be Glu-Tyr-Pro by gas phase sequencing, after hydrolysis of pyroglutamic acid by mild acid hydrolysis. The mass of the alfalfa tripeptide was 389.1, as determined by fast ion bombardment mass spectroscopy, and was found to be identical to the mass of synthetic pyroGlu-Tyr-Pro amide. The sequence of the alfalfa tripeptide was also verified using B/E-linked scanning. I conclude that the tripeptide isolated from alfalfa differs from human thyrotropin releasing hormone only by the substitution of tyrosine for histidine at position 2. The role of pyroGlu-Tyr-Pro amide in alfalfa is not known, but the existence of a family of thyrotropin-related peptides occurring in both the animal and the plant kingdoms indicates that the thyrotropin related peptides have a wide phylogenetic distribution. PMID- 1517204 TI - The small GTP-binding proteins in the cytosol of insulin-secreting cells are complexed to GDP dissociation inhibitor proteins. AB - Ras-related small GTP-binding proteins (SMGs) exist in a cytosolic and a membrane bound pool. The mechanism regulating the intracellular distribution of SMGs remains to be elucidated. We have, therefore, investigated the properties of SMGs expressed in cells of the insulin-secreting lines RINm5F and HIT-T15. Phase partitioning analysis revealed that smg25A/rab3A as well as all the SMGs in the 23-27 kDa range, labeled by radioactive GTP after blotting, were hydrophobic, regardless of their subcellular distribution. In contrast, the cytosolic forms of ADP ribosylation factor, rho, and CDC42 were hydrophilic. The cytosolic pool of the 23-27-kDa group, including smg25A/rab3A, sedimented in a sucrose density gradient as complexes with an apparent M(r) of about 80,000, whereas rho and CDC42 were recovered in 45-kDa complexes. ARF, however, was uncomplexed (M(r) close to 20,000). The 80-kDa aggregates were likely to be formed by 1:1 complexes with the regulatory protein smg25/GDP dissociation inhibitor (smg25/GDI). In fact, pure smg25/GDI by sucrose gradient exhibited a molecular mass of 55 kDa, but cosedimented with the 80-kDa complexes in cytosolic extracts of insulin secreting cells. Moreover, purified smg25/GDI was able to extract the SMGs of the 23-27-kDa group from the membranes. Similarly, in cytosolic extracts, rho/GDI cosedimented with the 45-kDa aggregates. Blocking the synthesis of isoprenoid groups with lovastatin resulted in the appearance in the cytosol of SMGs that were hydrophilic. These SMGs were found to sediment with an apparent M(r) close to 25,000 and to be unable to form complexes with smg25/GDI. Lovastatin treatment also caused the accumulation of the noncomplexed form of CDC42 but not of rho proteins. We propose that 1) except for ARF, all the SMGs detected in the cytosol of insulin-secreting cells are associated in 1:1 complexes with their regulatory proteins; 2) the different SMGs can be subdivided into functional groups according to the regulatory protein bound to them; 3) the formation of the 80-kDa complexes with smg25/GDI and of the CDC42 complexes with rho/GDI necessitate the correct carboxyl-terminal post-translational modification of the SMGs. PMID- 1517205 TI - Human factor IX has a tetrasaccharide O-glycosidically linked to serine 61 through the fucose residue. AB - We have recently discovered unusual sugar chains (xylose (Xyl)-glucose (Glc) and (Xyl)2-Glc) linked to a serine residue in the epidermal growth factor (EGF)-like domains of human and bovine clotting factors VII (Ser-52), IX (Ser-53), and protein Z (Ser-53), in addition to bovine platelet glycoprotein thrombospondin. We now have evidence of another modification in the first EGF-like domain of human factor IX, which proved to be a tetrasaccharide O-fucosidically linked to Ser-61. Two large peptides containing Ser-61 (positions 44-63), named hIX-GP1 and hIX-GP2, were first isolated from the lysyl endopeptidase-digest of human factor IX, by reversed-phase high performance liquid chromatography (HPLC). Data on the component sugar analysis after pyridylamination (PA) and sialic acid analysis of the isolated peptides indicated that they contained 1 mol each of galactose (Gal), fucose (Fuc), N-acetylglucosamine (GlcNAc), and N-acetylneuraminic acid (NeuAc), in addition to Glc and Xyl. hIX-GP1 was further digested with asparaginyl endopeptidase, and two glycopeptides containing Ser-61, named N-3 (positions 59-63) and N-9 (positions 55-63), were isolated, respectively. These glycopeptides were both composed of 1 mol each of Gal, Fuc, GlcNAc, and NeuAc but did not contain Xyl and Glc. Moreover, the data on beta-elimination for N-9 and of the fast atom bombardment mass spectrometric analysis on peptide N-3 suggested the presence of a tetrasaccharide linked to Ser-61. An analysis of the PA oligosaccharide released from hIX-GP1 by hydrazinolysis followed by pyridylamination revealed that the reducing end was PA-Fuc. All the results support the proposal that human factor IX has a novel tetrasaccharide consisting of 1 mol each of Gal, Fuc, GlcNAc, and NeuAc, which is O-glycosidically linked to Ser-61 through the Fuc residue. PMID- 1517206 TI - Resistance of smooth muscle cells to assembly of high density lipoproteins with extracellular free apolipoproteins and to reduction of intracellularly accumulated cholesterol. AB - Removal of intracellularly accumulated cholesterol by lipid-free human apolipoproteins (apo) A-I and A-II was studied for aortic smooth muscle cells (SMC) of rat, monkey and rabbit, human skin fibroblasts (FB), and mouse peritoneal macrophages (MP). The reaction generated high density lipoprotein (HDL)-like lipoproteins as did those and other helical apolipoproteins with MP, causing efflux of cellular cholesterol. From FB and MP, the maximum efflux rates with apoA-I and A-II per 24 h were as much as 30% of the apparent maximum efflux rate of prelabeled cellular cholesterol to human HDL. From rat SMC these rates were 7.2 and 6.8%, respectively, being independent of cellular cholesterol content. Those from monkey and rabbit SMC were also very low. When standardized for the initial cellular unesterified cholesterol pool size, the maximum efflux rates/24 h were 5.4 and 5.0% for apoA-I and A-II from rat SMC and even less from monkey and rabbit SMC in contrast to 42.4 and 39.7% from FB, and 53.0 and 45.5% from MP, respectively. The standardized apparent maximum efflux to HDL was 76% from rat SMC, 45 and 31% from monkey and rabbit SMC, 139% from FB and 166% from MP. Accordingly, the reaction with free apolipoproteins caused significant net reduction of cellular cholesterol, predominantly in cholesteryl ester, in FB and MP, but not in SMC. While the efflux Km with apoA-I and A-II were 7.5 and 4.5 micrograms/ml for MP, those for SMC and FB were both 1 microgram/ml or lower, as low as 1/1500 and 1/500 of their plasma concentrations, respectively. The apparent efflux Km for HDL were, on the other hand, all in the range of 36 to 65 micrograms of protein/ml for SMC, FB, and MP, showing that the mode of cholesterol exchange of these cells with lipoprotein surface is not significantly different from each other. Thus, peripheral cells such as FB may provide a significant source of HDL by interacting with extracellular free apolipoproteins in interstitial fluid, reducing intracellularly accumulated cholesterol. However, SMC seem very resistant to this interaction, suggesting that atheromatous lesions predominantly consisting of SMC are resistant to regression. PMID- 1517207 TI - Cell-specific glucocorticoid repression of calcitonin/calcitonin gene-related peptide transcription. Localization to an 18-base pair basal enhancer element. AB - We have investigated the mechanisms underlying cell-specific glucocorticoid repression of calcitonin/calcitonin gene-related peptide (CGRP) gene expression. Treatment with the synthetic glucocorticoid dexamethasone has been shown to decrease mRNA levels in the 44-2C thyroid C cell line. Nuclear run-on assays showed that dexamethasone repressed transcription 2-3-fold in 44-2C cells. In contrast, dexamethasone stimulated calcitonin/CGRP transcription 4-6-fold in the CA77 thyroid C cell line. Transient transfection assays were used to map repression of reporter gene activity in 44-2C cells to a neuroendocrine cell specific enhancer located between -920 and -1125 base pairs (bp). Within this region, an 18-bp element was found that conferred both full basal enhancer activity and dexamethasone-dependent repression in 44-2C cells. The 18-bp region contains possible binding sites for AP-1 and helix-loop-helix transcription factors as well as a glucocorticoid receptor half-site. Colocalization of repression and enhancer activity was then investigated in other cell lines. In CA77 cells, while the 920-1125 region strongly enhanced transcription, the 18-bp region conferred only partial activation and dexamethasone had little effect on reporter gene activity. Dexamethasone did not repress the calcitonin/CGRP activity in the heterologous HeLa and Rat1 fibroblast cell lines. These results suggest that glucocorticoids repress transcription of the calcitonin/CGRP gene by inhibiting cell-specific transcription factor activity. PMID- 1517208 TI - Biosynthesis of methanofuran in Methanobacterium thermoautotrophicum. AB - The 13C NMR signals of methanofuran were assigned by two-dimensional 1H and 13C NMR experiments. On this basis, the incorporation of 13C-labeled acetate and pyruvate into methanofuran by growing cells of Methanobacterium thermoautotrophicum was analyzed by one- and two-dimensional 13C NMR experiments. The data were analyzed by a retrobiosynthetic approach based on a comparison of labeling patterns in a variety of metabolites. The data show that the furan ring is formed by condensation of two molecules from the pyruvate/triose pool. The tetracarbocylic acid moiety is assembled from ketoglutarate, two molecules of acetyl CoA, and one molecule of carbon dioxide. PMID- 1517209 TI - Modulation of rat liver S-adenosylmethionine synthetase activity by glutathione. AB - Rat liver S-adenosylmethionine (AdoMet) synthetase appears as high-M(r) (tetramer) and low-M(r) (dimer) forms. Both are inhibited in the presence of GSSG at pH 8. The calculated Ki values are 2.14 and 4.03 mM for the high- and low-M(r) forms, respectively. No effect on enzyme activity was observed in the presence of GSH, but modulation of inhibition by GSSG can be obtained by addition of GSH. At a total glutathione concentration (GSH + GSSG) of 10 mM, a KOX of 1.74 was calculated for the high-M(r) form, whereas this constant was 2.85 for the low M(r) AdoMet synthetase. No incorporation of [35S]GSSG was observed in either of the enzyme forms, and inhibition of enzyme activity was correlated with dissociation of both AdoMet synthetases to a monomer. The data obtained in the presence of GSSG seem to suggest that oxidation leads to the formation of an intrasubunit disulfide. The possible regulation of AdoMet synthetase activity by the GSH/GSSG ratio is discussed, as well as its in vivo significance. PMID- 1517210 TI - Basic fibroblast growth factor-syndecan complex at cell surface or immobilized to matrix promotes cell growth. AB - Promotion of cell growth and differentiation by growth factors during early development and organ formation are both temporally and spatially very precise. Syndecan is a well characterized integral membrane proteoglycan that binds several extracellular matrix components via its heparan sulfate chains and is therefore suggested to participate in cell regulation. Syndecan-like molecules, as low affinity receptors for heparin-binding growth factors, have been recently suggested to also regulate growth factor activity. Heparin/heparan sulfate interaction is required before, e.g. basic fibroblast growth factor (bFGF) can associate with its high affinity cell surface receptors and trigger signal transduction. In this paper we show that syndecan, but not free heparan sulfate chains, can simultaneously bind both bFGF and extracellular matrix molecules. Moreover, increased DNA synthesis of 3T3 cells was observed when the 3T3 cells were exposed to beads coated with the fibronectin-syndecan-bFGF complex, indicating that bFGF remains biologically active even when immobilized to matrix via the heparan sulfate chains of syndecan. Finally, when bFGF was bound to the surface of another cell type (epithelial), co-culture with 3T3 cells stimulated 3T3 cell growth. Therefore, we suggest that syndecan-like molecules may determine sites of growth factor action at cell-matrix and cell-cell interfaces. PMID- 1517211 TI - Members of the steroid hormone receptor superfamily interact with TFIIB (S300 II). AB - The S300-II factor was discovered as an activator of ovalbumin gene transcription with the chicken ovalbumin upstream promoter-transcription factor (COUP-TF, Sagami, I., Tsai, S. Y., Wang, H., Tsai, M.-J., and O'Malley, B. W. (1986) Mol. Cell. Biol. 6, 4259-4267). Although S300-II does not bind DNA selectively, it stabilizes the binding of COUP-TF to its ciselement (Tsai, S. Y., Sagami, I., Wang, H., Tsai, M.-J., and O'Malley, B. W. (1987) Cell 50, 701-709). Purified S300-II is also required for steroid receptor-activated transcription. Cloning and sequencing of S300-II showed that it is the general transcription factor TFIIB. Specific protein-protein interactions between recombinant S300-II/TFIIB and three members of the steroid hormone receptor superfamily, COUP-TF, estrogen receptor, and progesterone receptor, indicate that S300-II/TFIIB is one of the targets of these transactivators. Interestingly, a truncated estrogen receptor construct containing only the N-terminal transcription activation function 1 did not interact with S300-II/TFIIB in our assay, revealing that individual transcription activation functions of a single steroid hormone receptor may contact different targets. Demonstration of a direct association of S300-II/TFIIB and COUP-TF, independent of additional "adaptor" proteins, suggests that members of the steroid hromone receptor superfamily facilitate the transcription of activated genes at least in part via protein-protein interactions with the general transcription factor TFIIB. PMID- 1517213 TI - Prostaglandin H synthase kinetics. The effect of substituted phenols on cyclooxygenase activity and the substituent effect on phenolic peroxidatic activity. AB - A series of p- and m-substituted phenols were examined for their effect on the cyclooxygenase activity of prostaglandin H synthase in 0.1 M phosphate buffer at pH 8.0 and 25.0 +/- 0.1 degrees C. A biphasic response was observed. At low concentrations phenols stimulate, but at higher concentrations inhibit, cyclooxygenase activity. Both enhancement and inhibition are increased by phenolic substituents which are electron-donating, quantified by Hammett sigma constants, and hydrophobic, quantified by Hantsch tau constants. The same series of substituted phenols was also reacted with compound II of prostaglandin H synthase at 4.0 +/- 0.5 degrees C. The compound II data fit the Hammett rho sigma equation; no hydrophobicity factors are required. Phenols inhibit cyclooxygenase activity by interfering with the binding of arachidonic acid to compound I and by competing directly with arachidonic acid as reducing substrates for compound I. Phenols stimulate cyclooxygenase activity by acting as reducing substrates for compound II, thereby accelerating the peroxidatic cycle. Phenols also protect the enzyme from self-catalyzed inactivation, most likely by removing the free radical of prostaglandin G2 by reducing it to prostaglandin G2. Kinetic parameters Km and kcat for cyclooxygenase activity were determined in the presence of phenols. Identical values of Km (15.3 +/- 0.5 mM) and kcat (89 +/- 2 s-1) were obtained regardless of which phenol was employed. Therefore these represent the true Km and kcat values for cyclooxygenase activity. PMID- 1517212 TI - Mutagenesis of human acetylcholinesterase. Identification of residues involved in catalytic activity and in polypeptide folding. AB - Evidence for the involvement of Ser-203, His-447, and Glu-334 in the catalytic triad of human acetylcholinesterase was provided by substitution of these amino acids by alanine residues. Of 20 amino acid positions mutated so far in human acetylcholinesterase (AChE), these three were unique in abolishing detectable enzymatic activity (less than 0.0003 of wild type), yet allowing proper production, folding, and secretion. This is the first biochemical evidence for the involvement of a glutamate in a hydrolase triad (Schrag, J.D., Li, Y., Wu, M., and Cygler, M. (1991) Nature 351, 761-764), supporting the x-ray crystal structure data of the Torpedo californica acetylcholinesterase (Sussman, J.L., Harel, M., Frolow, F., Oefner, C., Goldman, A., Toker, L. and Silman, I. (1991) Science 253, 872-879). Attempts to convert the AChE triad into a Cys-His-Glu or Ser-His-Asp configuration by site-directed mutagenesis did not yield effective AChE activity. Another type of substitution, that of Asp-74 by Gly or Asn, generated an active enzyme with increased resistance to succinylcholine and dibucaine; thus mimicking in an AChE molecule the phenotype of the atypical butyrylcholinesterase natural variant (D70G mutation). Mutations of other carboxylic residues Glu-84, Asp-95, Asp-333, and Asp-349, all conserved among cholinesterases, did not result in detectable alteration in the recombinant AChE, although polypeptide productivity of the D95N mutant was considerably lower. In contrast, complete absence of secreted human AChE polypeptide was observed when Asp-175 or Asp-404 were substituted by Asn. These two aspartates are conserved in the entire cholinesterase/thyroglobulin family and appear to play a role in generating and/or maintaining the folded state of the polypeptide. The x-ray structure of the Torpedo acetylcholinesterase supports this assumption by revealing the participation of these residues in salt bridges between neighboring secondary structure elements. PMID- 1517214 TI - The structure of a complex of bovine alpha-thrombin and recombinant hirudin at 2.8-A resolution. AB - Crystals of the complex of bovine alpha-thrombin with recombinant hirudin variant 1 have space group C222(1) with cell constants a = 59.11, b = 102.62, and c = 143.26 A. The orientation and position of the thrombin component was determined by molecular replacement and the hirudin molecule was fit in 2 magnitude of Fo - magnitude of Fc electron density maps. The structure was refined by restrained least squares and simulated annealing to R = 0.161 at 2.8-A resolution. The binding of hirudin to thrombin is generally similar to that observed in the crystals of human thrombin-hirudin. Several differences in the interactions of the COOH-terminal polypeptide of hirudin, specifically of residues Asp-55h, Phe 56h, Glu-57h, and Glu-58h, and a few differences in the interactions of the hirudin core, specifically of residues Asp-5h, Ser-19h, and Asn-20h, with thrombin from human thrombin-hirudin suggest that there is some flexibility in the binding of these 2 molecules. Most of the residues in the 9 subsites that bind fibrinopeptide A7-16 to thrombin also interact with the NH2-terminal domain of hirudin. The S1 subsite is a notable exception in that only 1 of its 6 residues, namely Ser-214, interacts with hirudin. The only difference between human and bovine thrombins that appears to influence the binding of hirudin is the replacement of Lys-149E by an acidic glutamate in the bovine enzyme. PMID- 1517215 TI - Escherichia coli serine hydroxymethyltransferase. The role of histidine 228 in determining reaction specificity. AB - Serine hydroxymethyltransferase has a conserved histidine residue (His-228) next to the lysine residue (Lys-229) which forms the internal aldimine with pyridoxal 5'-phosphate. This histidine residue is also conserved at the equivalent position in all amino acid decarboxylases and tryptophan synthase. Two mutant forms of Escherichia coli serine hydroxymethyltransferase, H228N and H228D, were constructed, expressed, and purified. The properties of the wild type and mutant enzymes were studied with substrates and substrate analogs by differential scanning calorimetry, circular dichroism, steady state kinetics, and rapid reaction kinetics. The conclusions of these studies were that His-228 plays an important role in the binding and reactivity of the hydroxymethyl group of serine in the one-carbon-binding site. The mutant enzymes utilize substrates and substrate analogs more effectively for a variety of alternate non-physiological reactions compared to the wild type enzyme. As one example, the mutant enzymes cleave L-serine to glycine and formaldehyde when tetrahydropyteroylglutamate is replaced by 5-formyltetrahydropteroylglutamate. The released formaldehyde inactivates these mutant enzymes. The loss of integrity of the one-carbon-binding site with L-serine in the two mutant forms of the enzyme may be the result of these enzymes not undergoing a conformational change to a closed form of the active site when serine forms the external aldimine complex. PMID- 1517216 TI - Isolation of prolyl-tRNA synthetase as a free form and as a form associated with glutamyl-tRNA synthetase. AB - Rat liver prolyl-tRNA synthetase was purified as a dimer of M(r) 60,000 subunits not associated with other aminoacyl-tRNA synthetases and as a form associated with glutamyl-tRNA synthetase. Proteolysis of the dimeric enzyme generated a less active form with M(r) 52,000 subunits and an inactive form with M(r) 40,000 subunits. A second species was isolated with polypeptides of M(r) 60,000 and 150,000. This form dissociated during gel filtration chromatography being partially resolved into the M(r) 150,000 and 60,000 components; glutamyl-tRNA synthetase was associated with the larger polypeptide and prolyl-tRNA synthetase with the smaller component. Antibodies against the M(r) 60,000 polypeptide reacted with the M(r) 60,000 and 150,000 polypeptides. Gel filtration of extracts revealed multiple forms of prolyl- and glutamyl-tRNA synthetase. Antibody against the M(r) 60,000 component detected the M(r) 60,000 and 150,000 polypeptides throughout the chromatogram; these forms could be partially separated by polyethylene glycol fractionation. The M(r) 150,000 and 60,000 polypeptides were detected by Western blot analysis of crude extracts prepared under several conditions. Antibody to prolyl-tRNA synthetase reacted with a M(r) 150,000 polypeptide of the aminoacyl-tRNA synthetase core complex identified previously as glutamyl-tRNA synthetase. PMID- 1517217 TI - Effects of insulin on steady state kinetics of GLUT4 subcellular distribution in rat adipocytes. Evidence of constitutive GLUT4 recycling. AB - We labeled rat adipocyte cell surface glucose transporters with an impermeable, photoreactive glucose analogue, 1,3-bis-(3-deoxy-D-glucopyranose-3-yloxy)-2 propyl 4-benzoylbenzoate (B3GL) and its radioactive tracer [3H]B3GL. The labeling did not affect glucose transporter subcellular distribution in basal and insulin stimulated adipocytes. When basal or insulin-stimulated adipocytes were labeled with [3H]B3GL and incubated at 37 degrees C in steady state, labeled GLUT4 was rapidly reduced at the cell surface and stoichiometrically recovered in microsomes without any change in GLUT4 protein levels in either pool. The labeled GLUT4 equilibrium exchange was found to be a simple first order process describable by two first order rate constants, one for internalization (k(in)) and the other for externalization (kex). Insulin affected both rate constants, reducing k(in) by 2.8-fold and increasing kex by 3.3-fold. It is concluded that GLUT4 constantly and rapidly recycles in adipocytes between the cell surface and its storage pool, and insulin increases the cell surface GLUT4 level in rat adipocytes by modulating both the internalization and the externalization steps of constitutively recycling GLUT4. PMID- 1517218 TI - Critical functional role of the COOH-terminal ends of longitudinal hydrophobic strips in alpha-helices of T4 lysozyme. AB - The sensitivity of bacteriophage T4 lysozyme function to amino acid substitutions at defined positions in and around the longitudinal, hydrophobic strips of 9 alpha-helices was assessed after systematic replacement of each residue in the protein with a series of 13 amino acids. The hydrophobic strips were defined by identifying the longitudinal sectors in the helices with the highest mean residue hydrophobicities. Sensitivity to mutation (the percentage of replacements leading to loss of function) was calculated for each residue in the following positions: whole protein, helices, hydrophobic strips, other positions within the helices, and various positions within the hydrophobic strips as well as their extensions beyond the helices. Substitutions at positions in the hydrophobic strips led more frequently to loss of function than substitutions in the protein as a whole. One subset, the COOH-terminal hydrophobic strip residues, is apparently critical; substitutions of these residues (but not of their NH2-terminal counterparts) led at least as frequently to loss of function as substitutions of solvent inaccessible residues, and nearly as frequently as substitutions of the most highly conserved residues. PMID- 1517219 TI - Effects of phospholipid and GTP on recombinant ADP-ribosylation factors (ARFs). Molecular basis for differences in requirements for activity of mammalian ARFs. AB - ADP-ribosylation factors (ARFs) are highly conserved approximately 20-kDa guanine nucleotide-binding proteins that were first identified based on their ability to stimulate the cholera toxin-catalyzed ADP-ribosylation of Gs alpha and thus activate adenylyl cyclase. Proteins with ARF activity have been characterized from different mammalian tissues and exhibited different requirements for activity, stability, and phospholipid. Based on molecular cloning and mRNA distribution, at least six mammalian ARFs, which fall into three classes, have been identified. To test whether individual ARFs might have different requirements for optimal activity, as judged by their ability to enhance cholera toxin ADP-ribosyltransferase activity, four ARFs from classes I, II, and III were produced as recombinant proteins in Escherichia coli and characterized. Recombinant bovine ARF 2 (rARF 2) and human ARF 3 (rARF 3) (class I), human ARF 5 (rARF 5, class II), and human ARF 6 (rARF 6, class III) differed in the effects of phospholipid and detergent on their ability to enhance cholera toxin activity; rARFs 2, 3, and 5 required dimyristoylphosphatidylcholine (DMPC) and cholate, whereas rARF 6 did not require phospholipid/detergent for activity. Further characterization of two of the more divergent ARFs (ARFs 2 and 6) showed that both exhibited guanosine 5'-O-(3-thio)triphosphate binding which was enhanced by DMPC/cholate. In the transferase assay, rARF 2 required approximately 4 microM GTP for half-maximal stimulation of toxin activity, whereas rARF 6 required 0.05 microM GTP. rARF 6 exhibited a delay in activation of toxin not detected with rARF 2 that may be related to a requirement for guanine nucleotide exchange and/or GTP binding. These findings are consistent with the conclusion that the highly conserved members of the ARF family have different requirements for optimal activity. PMID- 1517220 TI - Membrane topology of the pBR322 tetracycline resistance protein. TetA-PhoA gene fusions and implications for the mechanism of TetA membrane insertion. AB - The tetracycline resistance gene of pBR322 encodes a 41-kDa inner membrane protein (TetA) that acts as a tetracycline/H+ antiporter. Based on hydrophobicity profiles, we identified 12 potential transmembrane segments in TetA. We used oligonucleotide deletion mutagenesis to fuse alkaline phosphatase (PhoA) to the C terminal edge of each of the predicted periplasmic and cytoplasmic segments of TetA. In general, the PhoA activities of the TetA-PhoA fusions support a TetA topology model consisting of 12 transmembrane segments with the N and C termini in the cytoplasm. However, several TetA-PhoA fusions have unexpected properties. One PhoA fusion to a predicted cytoplasmic segment (C6) has high activity. However, previous protease accessibility studies on the related Tn10 TetA protein indicated that C6 is cytoplasmically localized as predicted (Eckert, B., and Beck, C. F. (1989) J. Biol. Chem. 264, 11663-11670). PhoA fusions to three predicted periplasmic segments (P1, P2, and P5) have low to intermediate activity. In each case, the preceding transmembrane segment (TM1, TM3, and TM9) contains an aspartate (Asp17, Asp86, and Asp287). We show that these aspartates act like signal sequence mutations for PhoA export: (i) Asp----Ala mutations increase the PhoA activity of fusions to P1, P2, and P5. (ii) The signal sequence mutation suppressor prlA402 increases the PhoA activity of these same fusions. We also show that the aspartates in TM1, TM3, and TM9 are critical for wild-type TetA function; they are conserved in related TetA proteins and Asp----Ala mutations reduce or eliminate tetracycline resistance. The properties of the anomalous TetA-PhoA fusions suggest that TetA sequences C-terminal to some cytoplasmic and periplasmic segments are required for the proper localization of those segments, i.e. long range interactions may be more important in determining the membrane topology of TetA than suggested in some general models. PMID- 1517221 TI - Interactions of the exchange inhibitory peptide with Na-Ca exchange in bovine cardiac sarcolemmal vesicles and ferret red cells. AB - The Na-Ca exchange inhibitory peptide (XIP), which corresponds to residues 251 270 of the Na-Ca exchange protein, specifically inhibits exchange activity (Li, Z., Nicoll, D. A, Collins, A., Hilgemann, D. W., Filoteo, A. G., Penniston, J. T., Weiss, J. N., Tomich, J. M., and Philipson, K. D. (1991) J. Biol. Chem. 266, 1014-1020). We have found that XIP decreased Na+i-dependent Ca2+ uptake to 46 and 20% of control in mixed and inside-out bovine sarcolemmal (SL) vesicles, respectively, and to 22% of control in ferret red cell vesicles. XIP inhibited uptake in bovine SL vesicles after proteolytic digestion. XIP also inhibited Na+o dependent Ca2+ efflux in bovine SL vesicles but did not inhibit Ca2+ uptake in reconstituted proteoliposomes. Extracellular XIP did not inhibit Ca2+ uptake into intact ferret red cells. Inhibition of uptake in bovine SL vesicles was reduced as the ionic strength was increased. 125I-labeled XIP (1 microM) was cross-linked to proteins of bovine SL vesicles, ferret red cell vesicles, and intact ferret red cells. Labeling of bands at approximately 75, 120, and 220 kDa (in bovine SL vesicles) and bands at 55 and 85 kDa (in ferret red cell vesicles) was detected. No cross-linking was detected in intact ferret red cells. We conclude that XIP inhibition is insensitive to proteolytic digestion and is partially dependent on charge association and conformation of the exchanger. XIP binds to and interacts with the intracellular side of the Na-Ca exchanger. PMID- 1517222 TI - Human leukotriene C4 synthase expression in dimethyl sulfoxide-differentiated U937 cells. AB - Leukotriene C4 (LTC4) synthase was highly expressed in the human U937 monoblast leukemia cell line when differentiated into monocyte/macrophage-like cells by growth in the presence of dimethyl sulfoxide. The specific activity of LTC4 synthase in differentiated cells (399.0 +/- 84.1 pmol of LTC4 formed.min-1.mg-1) was markedly higher (10-fold; p less than 0.001) than in undifferentiated U937 cells (39.9 +/- 16.7 pmol of LTC4 formed.min-1.mg-1) or freshly isolated blood monocytes (21.5 +/- 4.8 pmol of LTC4 formed.min-1.mg-1). The increase in LTC4 synthase activity following dimethyl sulfoxide-induced differentiation was substantially higher than the increase observed for other proteins involved in leukotriene biosynthesis. LTC4 synthase activity was unaffected in U937 cells differentiated by growth in the presence of phorbol 12-myristate 13-acetate. The HL-60 myeloblast leukemia cell line expressed higher LTC4 synthase levels when differentiated into either neutrophil-like or macrophage-like cells by growth in the presence of dimethyl sulfoxide or phorbol 12-myristate 13-acetate (respectively), but reached a specific activity comparable only to undifferentiated U937 cells. Human LTC4 synthase was found to be a unique membrane-bound enzymatic activity completely distinct from alpha, mu, pi, theta, and microsomal glutathione S-transferases, as determined by differential detergent solubilization, chromatographic separation, substrate specificity, and Western blot analysis. An 18-kDa polypeptide was specifically labeled in membranes from dimethyl sulfoxide-differentiated U937 cells using azido 125I LTC4, a photoaffinity probe based on the product of the LTC4 synthase-catalyzed reaction. Photolabeling of the 18-kDa polypeptide was specifically competed for by LTC4 (greater than 50% at 0.1 microM) but not by 100,000-fold higher concentrations of reduced glutathione (10 mM). Elevation of both the level of the specifically photolabeled 18-kDa polypeptide and of LTC4 synthase specific activity occurred concomitantly with dimethyl sulfoxide differentiation of U937 cells. We conclude that differentiation of U937 cells into monocyte/macrophage like cells by growth in the presence of dimethyl sulfoxide results in high levels of expression of LTC4 synthase activity. Human LTC4 synthase is a unique enzyme with a high degree of specificity for LTA4 and may therefore be dedicated exclusively to the formation of LTC4 in vivo. An 18-kDa membrane polypeptide, specifically labeled by a photoaffinity derivative of LTC4, is a candidate for being either LTC4 synthase or a subunit thereof. PMID- 1517223 TI - Characterization of the nucleic acid binding region of adenovirus DNA binding protein by partial proteolysis and photochemical cross-linking. AB - The nucleic acid binding domain of the adenovirus type 2 (or type 5) DNA-binding protein (DBP) was characterized by using limited proteolysis and photochemical cross-linking. Three proteases were used to generate fragments of DBP which retained the ability to bind to single-stranded DNA. One fragment, a 35-kDa tryptic product, was partially sequenced and found to contain amino acid residues 153 to approximately 470. This fragment further defines the minimum region of the protein which is required for nucleic acid binding. The DNA binding pocket of DBP was defined by using ultraviolet irradiation to cross-link covalently the carboxyl-terminal portion of the protein to the oligonucleotide p(dT)14. Cross linked complexes were digested with trypsin, and peptides which were associated with the oligonucleotide were isolated by anion-exchange and reverse-phase ion pairing high performance liquid chromatography. Two DBP peptides comprised of residues 294-308 and 415-434 were isolated by this approach. Sequence analysis indicated that methionine 299 and phenylalanine 418 were probable sites of cross linking between their respective peptides and the oligonucleotide; hence these residues may represent contact points between DBP and single-stranded DNA. Both residues are highly conserved and are near, but not identical to, regions of the protein implicated previously in DNA binding. PMID- 1517224 TI - Beta-arrestin2, a novel member of the arrestin/beta-arrestin gene family. AB - Homologous or agonist-specific desensitization of beta 2-adrenergic receptors (beta 2AR) is mediated by the beta-adrenergic receptor kinase (beta ARK) which specifically phosphorylates the agonist-occupied form of the receptor. However, the capacity of beta ARK-phosphorylated beta 2AR to stimulate Gs in a reconstituted system is only minimally impaired. Recently, a protein termed beta arrestin, was cloned from a bovine brain cDNA library and found to quench phosphorylated beta 2AR-coupling to Gs. Utilizing a low stringency hybridization technique to screen a rat brain cDNA library, we have now isolated cDNA clones representing two distinct beta-arrestin-like genes. One of the cDNAs is the rat homolog of bovine beta-arrestin (beta-arrestin1). In addition, we have isolated a cDNA clone encoding a novel, beta-arrestin-related protein which we have termed beta-arrestin2. Overall, beta-arrestin2 exhibits 78% amino acid identity with beta-arrestin1. The primary structure of these proteins delineates a family of proteins that regulates receptor coupling to G proteins. The capacity of purified beta-arrestin1, beta-arrestin2, and arrestin to inhibit the coupling of phosphorylated receptors to their respective G proteins were assessed in a reconstituted beta 2AR-Gs system and in a reconstituted rhodopsin-GT system. beta Arrestin2 was equipotent to beta-arrestin1 and specifically inhibited beta 2AR function. Conversely, arrestin inhibited rhodopsin coupling to GT, whereas beta arrestin1 and beta-arrestin2 were at least 20-fold less potent in this system. beta-Arrestin1 and beta-arrestin2 are predominantly localized in neuronal tissues and in the spleen. However, low mRNA levels can be detected in most peripheral tissues. In the central nervous system, beta-arrestin2 appears to be even more abundant than beta-arrestin1. Immunohistochemical analysis of the tissue distribution of beta-arrestin1 and beta-arrestin2 in rat brain shows extensive, but heterogenous, neuronal labeling of the two proteins. They are found in several neuronal pathways suggesting that they have relatively broad receptor specificity regulating many G protein-coupled receptors. Furthermore, immunoelectron microscopy shows that the beta-arrestins are appropriately situated at postsynaptic sites to act in concert with beta ARK to regulate G protein-coupled neurotransmitter receptors. PMID- 1517225 TI - Kinetics of HIV-1 long terminal repeat trans-activation. Use of intragenic ribozyme to assess rate-limiting steps. AB - We have examined, using self-cleaving ribozymes, the intracellular trans activation kinetics of the human immunodeficiency virus type 1 (HIV-1) long terminal repeat (LTR) by viral protein Tat. Experiments were designed to effect a competition (during RNA chain elongation) between cleavage of a nascent RNA containing the Tat-responsive target sequence (TAR) and Tat interaction with the same TAR in the process of LTR-trans-activation. We found that fast self-cleavage of nascent TAR-containing RNA abolished Tat trans-activation. Slowing the cleavage reaction kinetically rescued trans-activation. Based on our results, we conclude that the rate-limiting step in HIV-1 LTR trans-activation is the initial contact made between Tat/TAR/LTR rather than the promoter proximal pausing of RNA polymerases that are tethered to functional TAR. PMID- 1517226 TI - The anchoring filament protein kalinin is synthesized and secreted as a high molecular weight precursor. AB - Kalinin, a recently characterized novel protein component of anchoring filaments, has been shown to be involved in keratinocyte attachment to culture substrates and to dermis in vivo, and to exist in keratinocyte-conditioned culture medium in two heterotrimeric forms of 440 and 400 kDa (Rousselle, P., Lunstrum, G.P., Keene, D.R., and Burgeson, R.E. (1991) J. Cell Biol. 114, 567-576). This study demonstrates that kalinin is initially synthesized in a cell-associated form estimated to be 460 kDa. By second dimension reduced electrophoresis, V8 protease digestion, and immunoblot analysis, we demonstrate that the cell form contains nonidentical subunits of 200, 155, and 140 kDa. The 440-kDa medium form is derived from the cell form by extracellular processing of the 200-kDa subunit to 165 kDa, a step which also occurs in skin organ culture. The 400-kDa form is derived from the 440-kDa form by extracellular processing of the 155 kDa-subunit to 105 kDa. The cell form is secreted by keratinocytes, deposited onto culture substratum, and is the form which facilitates attachment and adhesion of growing and spreading keratinocytes. It is also the form initially synthesized in skin organ culture. Kalinin purified from tissue, which appears to facilitate epithelial-mesenchymal cohesion in vivo, is closely related to the 400-kDa medium form purified from culture. PMID- 1517227 TI - A common trans-acting factor, Ad4-binding protein, to the promoters of steroidogenic P-450s. AB - Previous studies of bovine CYP11B1 gene regulation revealed six cis-acting elements, Ad1, Ad2, Ad3, Ad4, Ad5, and Ad6, in the 5' upstream region of the gene. Ad4 site was a positive transcription element in the stimulation by cAMP. Ad4-binding protein (Ad4BP) was purified from the nuclear extract of bovine adrenal cortex using affinity latex particles conjugated with polymerized Ad4 sequences. The molecular mass of the purified Ad4BP estimated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis was approximately 53 kDa. To characterize the binding specificity of Ad4BP, oligonucleotides homologous to Ad4 sequence and AGGTCA containing sequences in the promoter regions of steroidogenic P-450s were synthesized and used for gel shift analyses as competitors. The competition experiments revealed that Ad4BP bound not only to (C/T)CAAGG(T/C)(C/T), which was originally identified as the Ad4 binding site, but also to (Pu)PuPuAGGTCA. All the steroidogenic P-450 genes examined had at least one Ad4BP binding sequence. Experiments with model sequences containing various nucleotide substitutions established that (C/T)CAAGG(T/C)CA is the strongest binding sequence for Ad4BP. The expression of Ad4BP was examined with adrenal cortex cells and several other steroidogenic and nonsteroidogenic cells. Only the steroidogenic cells, the granulosa cells of bovine ovary, and I-10 cells derived from mouse Leydig cells, expressed the binding activity to Ad4 site. The presence of Ad4 site as a common cis-acting element in the genes of all the steroidogenic P-450s and the steroidogenic tissue-specific expression of Ad4BP strongly suggests that Ad4BP is an indispensable transcription factor for the expression of all the steroidogenic P-450 genes. PMID- 1517228 TI - FAD-dependent regulation of transcription, translation, post-translational processing, and post-processing stability of various mitochondrial acyl-CoA dehydrogenases and of electron transfer flavoprotein and the site of holoenzyme formation. AB - The most prominent biochemical consequence of riboflavin deficiency in rats is a drastic decrease in various acyl-CoA dehydrogenase activities, especially that of short chain and isovaleryl-CoA dehydrogenase (IVD). As a result, oxidation of fatty acids and leucine is severely inhibited. We studied the effects of FAD at various stages of acyl-CoA dehydrogenase biogenesis. Immunoblot revealed severe losses of various acyl-CoA dehydrogenases and electron transfer flavoprotein in riboflavin-deficient rat liver mitochondria. The decreases in IVD and short chain acyl-CoA dehydrogenase were particularly severe, reaching values of 17 and 34% of controls, respectively. With the exception of IVD, the rate of in vitro transcription of the respective genes and the amounts of mRNAs of these flavoproteins in tissues increased 3-8.5-fold over controls. The amount of IVD mRNA and its transcription rate remained unchanged, suggesting that IVD expression is regulated separately from other acyl-CoA dehydrogenases. When riboflavin was depleted, in vitro translation of acyl-CoA dehydrogenase and electron transfer flavoprotein alpha-subunit mRNAs was moderately inhibited. Translation of non-flavoproteins was also inhibited. The stability of precursor acyl-CoA dehydrogenases and their mitochondrial import/processing were unaffected. However, mature acyl-CoA dehydrogenases degraded markedly faster in deficient mitochondria than in controls. Regardless of whether precursors were translated under riboflavin-depleted or riboflavin replete conditions, mature acyl-CoA dehydrogenases survived well when imported into normal mitochondria but degraded faster when imported into deficient mitochondria. These findings indicate that FAD ligand binds to mature acyl-CoA dehydrogenase inside the mitochondria. PMID- 1517229 TI - Elevated levels of protein kinase C in Y1 cells which express apolipoprotein E decrease basal steroidogenesis by inhibiting expression of P450-cholesterol side chain cleavage mRNA. AB - We have previously reported that steroidogenesis is dramatically reduced in mouse Y1 adrenocortical cells which express the human apolipoprotein E gene (Y1-E cells). This suppression results in part from inhibition of cAMP-mediated events. In this report we have examined the expression of protein kinase C (PKC) in the Y1-E cell lines. Total cellular PKC activity in vitro is increased 3-5-fold in the Y1-E cell lines. PKC activity in the particulate and cytosolic fractions is increased to the same relative extent. Increased PKC activity reflects increased levels of PKC mRNA, as determined by Northern blot analysis, and PKC protein, as determined by immunoblot analysis. Increased expression of PKC in the Y1-E cell lines is accompanied by a 2-3-fold increase in diacylglycerol, an in vivo activator of PKC. To determine the contribution of elevated PKC expression to the Y1-E cell phenotype, we utilized the PKC inhibitors, staurosporine and calphostin C. Upon treatment with staurosporine or calphostin C, expression of P450 cholesterol side chain cleavage mRNA is increased severalfold to a level equal to, or greater than, basal expression in the Y1-neo control cell line. Treatment with calphostin C also results in recovery of steroidogenesis in the Y1-E cells to a level comparable to the basal level observed in the Y1-neo control cell line. These results indicate that increased expression of PKC in the Y1-E cell lines decreases basal steroidogenesis by suppressing P450-cholesterol side chain cleavage mRNA expression. Inhibition of PKC, however, does not reverse the block in cAMP-stimulated steroidogenesis in Y1-E cells, suggesting that the pleiotropic effects of apoE expression are not mediated entirely through altered PKC expression. PMID- 1517230 TI - Human ETS1 oncoprotein. Purification, isoforms, -SH modification, and DNA sequence-specific binding. AB - The human ETS1 proto-oncogene proteins have been isolated from the T-cell leukemia line, CEM, by immunoaffinity chromatography and their identity confirmed by NH2-terminal amino acid sequencing. Incubation of CEM cells with N alpha-p tosyl-L-lysine chloromethyl ketone (TLCK) indicates that ETS proteins can be modified in their cellular context and that pretreatment of the cells with N ethylmaleimide (NEM) protects ETS1 proteins from TLCK modification. These data show that ETS1 proteins can exist in at least two different states, -SH-available and -SH-protected. Renatured human ETS1 has DNA sequence-specific binding to the PEA3 (CAGGAAGT) motif. The ETS1.PEA3 complex can be observed by electrophoretic mobility shift assays (EMSA). Purified ETS1 retards a band which is exactly the same size as a complex that is retarded from nuclear extracts prepared from CEM cells. Reduced ETS1 is required to form the ETS1.PEA3 complex, however; modification of the ETS1 -SH groups by either NEM or by TLCk does not inhibit formation of the complex. The ETS1.PEA3 complex formed with TLCK-modified ETS1 has a slower mobility than the complex formed with unmodified ETS1. Zone sedimentation analysis of purified ETS1 indicates that it is the monomer of ETS1 which binds to the PEA3 oligonucleotide. PMID- 1517231 TI - Reconstitution, identification, purification, and immunological characterization of the 110-kDa Na+/Ca2+ antiporter from beef heart mitochondria. AB - The mitochondrial Na+/Ca2+ antiporter plays a key role in the physiological regulation of intramitochondrial Ca2+, which in turn attunes mitochondrial enzymes to the changing demands of the cell for ATP. We have now purified the Na+/Ca2+ antiporter from beef heart mitochondria by assaying detergent solubilized chromatography fractions for reconstitutive activity. Na+ and Ca2+ transport were assayed using the fluorescent probes, sodium-binding benzofuran isophthalate and Fura-2, respectively. This approach enabled us to identify Na+/Ca2+ exchange activity with a 110-kDa inner membrane protein that catalyzed Na(+)-dependent Ca2+ transport and Ca(2+)-dependent Na+ transport. A new finding was that the Na+/Ca2+ antiporter also catalyzed Na+/Li+ exchange in the absence of Ca2+. All modes of transport were electroneutral and were inhibited by diltiazem and tetraphenylphosphonium cation. Monospecific polyclonal antibodies to the 110-kDa protein inhibited Na+/Ca2+ and Na+/Li+ exchange in the reconstituted system and recognized 110-kDa proteins in mitochondrial membranes isolated from rat heart, liver, and kidney. PMID- 1517232 TI - Tissue factor potentiates the factor VIIa-catalyzed hydrolysis of an ester substrate. AB - We designed a simple and sensitive method to assay the activity of the factor VIIa-tissue factor complex, using as a substrate N alpha-benzyloxycarbonyl-L arginine p-nitrobenzyl ester (Z-Arg-ONb) (Zur, M., and Nemerson, Y. (1978) J. Biol. Chem. 253, 2203-2209). The principle was to measure the amount of p nitrobenzyl alcohol released during ester hydrolysis using reversed-phase high performance liquid chromatography. Z-Arg-ONb had a broad specificity for plasma serine proteases and factor IXa. Using this method, we examined the effect of tissue factor on the esterase activity of factor VIIa under various conditions. We found that tissue factor greatly potentiates the factor VIIa-catalyzed hydrolysis of Z-Arg-ONb. Phospholipids were not required for the factor VIIa catalyzed hydrolysis of Z-Arg-ONb, even in the presence of tissue factor. The Km value of factor VIIa alone toward the ester substrate was six times higher than that of a VIIa-tissue factor complex (3.2 versus 0.54 mM), whereas the kcat value was 12 times lower than that of the VIIa-tissue factor complex (14.3 versus 173 s 1). Thus, tissue factor apparently affects the catalytic site of factor VIIa and enhances hydrolysis of the ester substrate. This enhancing effect of tissue factor disappeared on removal of the gamma-carboxyglutamic acid domain from factor VIIa, whereas the esterase activity in the absence of tissue factor was not affected by this modification. The gamma-carboxyglutamic acid domain is probably required as a potent determinant for interactions with tissue factor, even in the absence of phospholipids in the reaction mixture. PMID- 1517233 TI - Direct evidence that J chain regulates the polymeric structure of IgM in antibody secreting B cells. AB - IgM is secreted in two functional polymeric forms. Secreted IgM was originally thought to be exclusively a pentameric molecule containing J (joining) chain, but many B cells also secrete hexameric IgM lacking J chain. Hexameric IgM may play an important role in the immune system, since it is up to 20 times more active than pentameric IgM in initiating the complement cascade. The predominant polymeric form of IgM secreted by B cell lines, either pentameric or hexameric, correlates with the concentration of J chain present during polymerization, and cells that express high levels of J chain secrete mostly IgM pentamers. The B cell lymphoma WEHI-231 does not express J chain, and the majority of its secreted IgM is polymerized as hexamers. When a J chain-encoding cDNA was expressed in these cells, the secreted IgM was found to be almost exclusively pentameric. However, although the expression of J chain dramatically altered the phenotype of the IgM secreted by these cells, it had little effect on their secretory rate. We conclude that J chain regulates the structure and function of the IgM polymers secreted by B cells, but it is not necessary for either IgM polymerization or secretion. PMID- 1517234 TI - Effect of sodium butyrate on estrogen receptor and epidermal growth factor receptor gene expression in human breast cancer cell lines. AB - Estrogen receptor (ER) binding has been shown to decrease in breast cancer cell lines exposed to sodium butyrate; however, the underlying mechanisms are unknown. In MCF-7 breast cancer cells, butyrate caused a rapid time- and concentration dependent decrease in ER mRNA levels, apparent by 3 h at 3 mM butyrate. ER gene transcription rate was decreased and cycloheximide co-treatment did not relieve this inhibitory effect, suggesting that the butyrate effect was not dependent on ongoing protein synthesis. In both MCF-7 and T-47D cells the decrease in ER mRNA was mirrored by an increase in the level of epidermal growth factor receptor (EGF R) mRNA. A marked inverse relationship exists between ER and EGF-R in human breast cancer biopsies and cell lines, and the reciprocal modulation of these genes by butyrate suggests that the expression of ER and EGF-R may be co regulated. This relationship was further investigated in lines expressing only one or the other receptor. In the ER-positive EGF-R-negative line, MDA-MB-134-VI, butyrate exposure decreased ER mRNA levels, implying that the regulation of ER mRNA by butyrate is independent of EGF-R expression. However, butyrate decreased EGF-R mRNA in two ER-negative lines, MDA-MB-231 and HBL-100. As this effect differed from that in ER-positive lines, the regulation of EGF-R may depend on the expression of ER. The possibility that ER and EGF-R gene expression are closely linked has implications in the understanding of progression of human breast cancers to a hormone-independent phenotype and for the use of ER and EGF-R levels as independent prognostic indicators. PMID- 1517235 TI - The 45- and 104-kDa forms of phosphatidate phosphatase from Saccharomyces cerevisiae are regulated differentially by phosphorylation via cAMP-dependent protein kinase. AB - Evidence is presented that demonstrated that the 45- and 104-kDa forms of phosphatidate phosphatase from Saccharomyces cerevisiae (Morlock, K. R., McLaughlin, J. J., Lin, Y.-P., and Carman, G. M. (1991) J. Biol. Chem. 266, 3586 3593) were regulated differentially by phosphorylation. Purified 45-kDa phosphatidate phosphatase was phosphorylated by cAMP-dependent protein kinase whereas purified 104-kDa phosphatidate phosphatase was not phosphorylated. cAMP dependent protein kinase catalyzed the phosphorylation of pure 45-kDa phosphatidate phosphatase at a serine residue which resulted in a stimulation (2.4-fold) of phosphatidate phosphatase activity. Alkaline phosphatase catalyzed the dephosphorylation of pure 45-kDa phosphatidate phosphatase which resulted in an inhibition (1.3-fold) of phosphatidate phosphatase activity. Results of studies using mutants (bcy1 and cyr1) defective in cAMP-dependent protein kinase activity corroborated the results of the phosphorylation studies using pure preparations of phosphatidate phosphatase. The 45-kDa phosphatidate phosphatase phosphorylated in vitro and in vivo had phosphopeptides in common. The activation of the GAL10-RAS2val19 allele in mutant cells resulted in an increase in the synthesis of diacylglycerols and triacylglycerols. These results were consistent with the phosphorylation and activation of 45-kDa phosphatidate phosphatase by cAMP-dependent protein kinase in vivo. PMID- 1517237 TI - Identification of an estrogen response element in the 3'-flanking region of the murine c-fos protooncogene. AB - We have used transient transfection assays with reporter plasmids expressing chloramphenicol acetyltransferase, linked to regions of mouse c-fos, to identify a specific estrogen response element (ERE) in this protooncogene. This element is located in the untranslated 3'-flanking region of the c-fos gene, 5 kilobases (kb) downstream from the c-fos promoter and 1.5 kb downstream of the poly(A) signal. This element confers estrogen responsiveness to chloramphenicol acetyltransferase reporters linked to both the herpes simplex virus thymidine kinase promoter and the homologous c-fos promoter. Deletion analysis localized the response element to a 200-base pair fragment which contains the element GGTCACCACAGCC that resembles the consensus ERE sequence GGTCACAGTGACC originally identified in Xenopus vitellogenin A2 gene. A synthetic 36-base pair oligodeoxynucleotide containing this c-fos sequence conferred estrogen inducibility to the thymidine kinase promoter. The corresponding sequence also induced reporter activity when present in the c-fos gene fragment 3 kb from the thymidine kinase promoter. Gel-shift experiments demonstrated that synthetic oligonucleotides containing either the consensus ERE or the c-fos element bind human estrogen receptor obtained from a yeast expression system. However, the mobility of the shifted band is faster for the fos-ERE-complex than the consensus ERE complex suggesting that the three-dimensional structure of the protein-DNA complexes is different or that other factors are differentially involved in the two reactions. When the 5'-GGTCA sequence present in the c-fos ERE is mutated to 5'-TTTCA, transcriptional activation and receptor binding activities are both lost. Mutation of the CAGCC-3' element corresponding to the second half-site of the c-fos sequence also led to the loss of receptor binding activity, suggesting that both half-sites of this element are involved in this function. The estrogen induction mediated by either the c-fos or the consensus ERE was blunted by the antiestrogen tamoxifen. Based on these studies, we believe the 3'-fos ERE sequence we have identified may be a major cis-acting element involved in the physiological regulation of the gene by estrogens in vivo. PMID- 1517236 TI - Cdc25 regulates the phosphorylation and activity of the Xenopus cdk2 protein kinase complex. AB - The Xenopus cdk2 gene encodes a 32-kDa protein kinase with sequence similarity to the 34-kDa product of the cdc2 gene. Previous studies have shown that the kinase activity of the protein product of the cdk2 gene oscillates in the Xenopus embryonic cell cycle with a high in M-phase and a low in interphase. In the present study cdk2 was found not to be associated with any newly synthesized proteins during the cell cycle, but the enzyme did undergo periodic changes in phosphorylation. Upon exit from metaphase, cdk2 became increasingly phosphorylated on both tyrosine and serine residues, and labeling on these residues increased progressively until entry into mitosis, when tyrosine residues were markedly dephosphorylated. Phosphopeptide mapping of cdk2 demonstrated the major sites of phosphorylation were in a phosphopeptide with a pI of 3.7 that contained both phosphoserine and phosphotyrosine. This phosphopeptide accumulated in egg extracts blocked in S-phase with aphidicolin and was not evident in cdc2 immunoprecipitated under the same conditions. Under the same conditions cdc2 was phosphorylated primarily on a phosphopeptide containing both phosphothreonine and phosphotyrosine residues, most likely threonine 14 and tyrosine 15. Affinity purified human GST-cdc25 was able to dephosphorylate and activate cdk2 isolated from interphase cells. Phosphopeptide mapping demonstrated that the phosphate was specifically removed from the same phosphopeptide identified as the major in vivo site of phosphorylation. These results demonstrate that cdk2 is regulated in the cell cycle by phosphorylation and dephosphorylation on both serine and tyrosine residues. Moreover, the increased phosphorylation of cdk2 in aphidicolin-blocked extracts and the ability of cdc25 to mediate cdk2 dephosphorylation in vitro suggest the possibility that cdk2 is part of the mechanism ensuring mitosis is not initiated until completion of DNA replication. It also implies cdc25 may have other functions in addition to the regulation of cdc2 kinase activity. PMID- 1517238 TI - Identification of essential histidine residues in rat type I iodothyronine deiodinase. AB - Deiodination is required for conversion of thyroxine, the inactive prohormone secreted by the thyroid gland, to 3,5,3'-triiodothyronine, the biologically active thyroid hormone. The principal enzyme catalyzing this reaction, Type I iodothyronine 5' deiodinase, was shown recently to contain the amino acid, selenocysteine, and site-directed mutagenesis showed that this amino acid confers the biochemical properties characteristic of this enzyme. Previous studies suggest that a histidine residue may also be critical for activity. To further our understanding of the biochemical mechanism of this reaction, we have used in vitro mutagenesis to examine the contribution of each of the 4 histidines in this enzyme to the deiodination process. Two of the histidines (185 and 253) are not involved in deiodination, as their removal had no effect on activity. Mutagenesis of histidine 158 resulted in complete loss of activity, suggesting a role in either protein conformation or catalysis. The most informative results were obtained from the studies of histidine 174. Mutagenesis of this histidine to asparagine or glutamine altered reactivity with substrate and reduced inhibition by diethylpyrocarbonate and rose bengal. These results demonstrate that histidine 174 is critical to function and appears to be involved in binding of hormone. PMID- 1517239 TI - Molecular cloning of porcine soluble angiotensin-binding protein. AB - Soluble angiotensin-binding protein (sABP) is a 75-kDa cytosolic protein that binds angiotensins and its analogues with high affinity. In this study, the primary structure of porcine sABP is determined by cDNA cloning. Based on the partial amino acid sequences of sABP tryptic fragments, fully degenerate oligonucleotides were synthesized, and used as primers for polymerase chain reactions to amplify the corresponding sABP cDNA fragment from porcine liver first-strand cDNA. By using initially the polymerase chain reaction product and later partial cDNA clones as probes, porcine heart and liver cDNA libraries were screened, and several positive clones were obtained including one covering the entire coding region. From the cDNA sequence, an open reading frame that encodes sABP as a 704-amino acid protein with molecular mass of 80,800 daltons is predicted. No significant homology was seen between sABP and other proteins in GenBank and NBRF data bases, including the angiotensin-related proteins such as angiotensin converting enzyme, renin, and AT1 angiotensin II receptor. Northern blot analysis of poly(A)+ RNA revealed that the mRNA for sABP is expressed as 5.3 and 2.8-3.2-kilobase transcripts. These transcripts are generated by the use of alternative polyadenylation signals. Within the 3'-untranslated region of the cDNA sequence downstream from the polyadenylation signals for smaller transcripts, a porcine short interspersed repetitive element (SINE) was found; only the longer 5.3-kilobase transcript had the SINE sequence. PMID- 1517240 TI - Gene structure of semenogelin I and II. The predominant proteins in human semen are encoded by two homologous genes on chromosome 20. AB - The genes for semenogelin I and II, the major protein constituents of the human seminal fluid, have been characterized by three overlapping clones in bacteriophage lambda, encompassing 31.5 kilobases (kb) of genomic DNA. The two genes are located 11.5 kb apart in the region q12-q13.1 on chromosome 20. Both genes are relatively compact, spanning only 2.7 and 3.1 kb, respectively. The transcription units are composed of three exons, of which the first encodes the signal peptide, the second encodes the secreted protein, while the third solely contains 3'-noncoding nucleotides. The nucleotide sequences exhibit a similarity of close to 90% in the exons and exceeding 80% in the introns and flanking nucleotides. PMID- 1517242 TI - Regulation of gene expression of proteasomes (multi-protease complexes) during growth and differentiation of human hematopoietic cells. AB - We have reported that proteasomes are expressed at abnormally high levels in various hematopoietic tumor cells (Kumatori, A., Tanaka, K., Inamura, N., Sone, S., Ogura, T., Matsumoto, T., Tachikawa, T., Shin, S., and Ichihara, A. (1990) Proc. Natl. Acad. Sci. U.S.A. 87, 7071-7075). In the present study, we examined changes in the expressions of proteasomes during growth of peripheral T lymphocytes from healthy adults and differentiation of human leukemic cell lines. Up-regulation of mRNAs encoding multiple proteasome subunits was observed during proliferation of resting T-cells induced by mitogens such as phytohemagglutinin and interleukin-2. In contrast, in vitro terminal differentiation into monocytic, granulocytic, and erythroid cells of various immature leukemic cell lines, such as HL-60 promyelocytic leukemia cells and K562 erythroleukemia cells, by various inducing agents caused rapid and marked down-regulation of proteasomes expression, independently of the cell type, direction of differentiation, or type of signal. The syntheses of proteasome subunits of 21-31 kDa and their associated components of 35-110 kDa, measured by [35S]methionine incorporation, were much higher in mitogen-activated T-cells and unstimulated HL-60 cells, which grow rapidly, than in resting and differentiated cells, indicating apparent correlations of the mRNA levels of proteasomes with their translational activities. However, immunochemically, no detectable difference in the cellular contents of proteasomes was found in these cells in induced and uninduced states for proliferation and differentiation, suggesting accelerated turnover of proteasomes in rapidly proliferating cells. Inhibition of proteasome expression by an antisense oligodeoxynucleotide for the largest proteasome subunit, C2, caused partial arrest of cell cycle progression of T-lymphocytes, suggesting that up-regulation of proteasomes is indispensable for proliferation of the cells. We also observed that the nuclear fraction of proteasomes increased in proliferating T-cells and that proteasomes moved rapidly between the nucleus and cytoplasm during differentiation of HL-60 cells. PMID- 1517241 TI - A molecular model of RGD ligands. Antibody D gene segments that direct specificity for the integrin alpha IIb beta 3. AB - Following an ill-defined activation event, the Arg-Gly-Asp (RGD) recognition site of the platelet integrin, glycoprotein IIb-IIIa (alpha IIb beta 3), can bind to fluid-phase, RGD-containing protein ligands, such as fibrinogen, or to the murine monoclonal IgM, PAC-1, which contains the sequence Arg-Tyr-Asp (RYD) within the third complementarity-determining region of its heavy chain (H3). PAC-1 has thus become a widely exploited marker of platelet alpha IIb beta 3 activation. In this report, we compare PAC-1 with two murine IgG, OP-G2 (IgG1 kappa) and LJ-CP3 (IgG1 kappa), that also contain the sequence RYD in H3 but bind to alpha IIb beta 3 without prior activation. Each antibody can inhibit the binding of the other two to intact platelets or to purified IIb-IIIa, the binding of each antibody is completely inhibited by peptides containing RGD, and H3 of each antibody uses the germline D-gene DSP 2.10 (CTATAGGTACGAC) which includes the sequence RYD. Two other murine IgG, HP20 and PCG1-1, cloned and sequenced by other laboratories, also utilize the DSP 2.10 sequence, but neither antibody binds to alpha IIb beta 3. From a comparison of the H3 sequences of these antibodies, we have developed a molecular model of the H3 loop region which can explain these differences in specificity. This model predicts that both the ability to bind to alpha IIb beta 3 and the activation dependence of that binding are a function of the orientation and, therefore, accessibility of the RYD sequence. This model and refinements thereof can be exploited to study the molecular basis for specificity and affinity of RGD-containing ligands for integrins. PMID- 1517243 TI - Video imaging of cytosolic Ca2+ in pancreatic beta-cells stimulated by glucose, carbachol, and ATP. AB - In order to define the differences in the distribution of cytosolic free Ca2+ ([Ca2+]i) in pancreatic beta-cells stimulated with the fuel secretagogue glucose or the Ca(2+)-mobilizing agents carbachol and ATP, we applied digital video imaging to beta-cells loaded with fura-2.83% of the cells responded to glucose with an increase in [Ca2+]i after a latency of 117 +/- 24 s (mean +/- S.E., 85 cells). Of these cells, 16% showed slow wave oscillations (frequency 0.35/min). In order to assess the relationship between membrane potential and the distribution of the [Ca2+]i rise, digital image analysis and perforated patch clamp methods were applied simultaneously. The system used allowed sufficient temporal resolution to visualize a subplasmalemmal Ca2+ transient due to a single glucose-induced action potential. Glucose could also elicit a slow depolarization which did not cause Ca2+ influx until the appearance of the first of a train of action potentials. [Ca2+]i rose progressively during spike firing. Inhibition of Ca2+ influx by EGTA abolished the glucose-induced rise in [Ca2+]i. In contrast, the peak amplitude of the [Ca2+]i response to carbachol was not significantly different in normal or in Ca(2+)-deprived medium. Occasionally, the increase of the [Ca2+]i rise was polarized to one area of the cell different from the subplasmalemmal rise caused by glucose. The amplitude of the response and the number of responding cells were significantly increased when carbachol was applied after the addition of high glucose (11.2 mM). ATP also raised [Ca2+]i and promoted both Ca2+ mobilization and Ca2+ influx. The intracellular distribution of [Ca2+]i was homogeneous during the onset of the response. A polarity in the [Ca2+]i distribution could be detected either in the descending phase of the peak or in subsequent peaks during [Ca2+]i oscillations caused by ATP. In the absence of extracellular Ca2+, the sequential application of ATP and carbachol revealed that carbachol was still able to raise [Ca2+]i after exhaustion of the ATP response. This may be due to desensitization to the former agonist, since the response occurred in the same area of the cell. These results reveal subtle differences in [Ca2+]i distribution following membrane depolarization with glucose or the application of Ca(2+)-mobilizing agonists. PMID- 1517244 TI - Mechanism of Ca2+ wave propagation in pancreatic acinar cells. AB - An increase in cytosolic Ca2+ often begins as a Ca2+ wave, and this wave is thought to result from sequential activation of Ca(2+)-sensitive Ca2+ stores across the cell. We tested that hypothesis in pancreatic acinar cells, and since Ca2+ waves may regulate acinar Cl- secretion, we examined whether such waves also are important for amylase secretion. Ca2+ wave speed and direction was determined in individual cells within rat pancreatic acini using confocal line scanning microscopy. Both acetylcholine (ACh) and cholecystokinin-8 induced rapid Ca2+ waves which usually travelled in an apical-to-basal direction. Both caffeine and ryanodine, at concentrations that inhibit Ca(2+)-induced Ca2+ release (CICR), markedly slowed the speed of these waves. Amylase secretion was increased over 3 fold in response to ACh stimulation, and this increase was preserved in the presence of ryanodine. These results indicate that 1) stimulation of either muscarinic or cholecystokinin-8 receptors induces apical-to-basal Ca2+ waves in pancreatic acinar cells, 2) the speed of such waves is dependent upon mobilization of caffeine- and ryanodine-sensitive Ca2+ stores, and 3) ACh-induced amylase secretion is not inhibited by ryanodine. These observations provide direct evidence that Ca(2+)-induced Ca2+ release is important for propagation of cytosolic Ca2+ waves in pancreatic acinar cells. PMID- 1517245 TI - Ferritin: a cytoprotective antioxidant strategem of endothelium. AB - Phagocyte-mediated oxidant damage to vascular endothelium is likely involved in various vasculopathies including atherosclerosis and pulmonary leak syndromes such as adult respiratory distress syndrome. We have shown that heme, a hydrophobic iron chelate, is rapidly incorporated into endothelial cells where, after as little as 1 h, it markedly aggravates cytotoxicity engendered by polymorphonuclear leukocyte oxidants or hydrogen peroxide (H2O2). In contrast, however, if cultured endothelial cells are briefly pulsed with heme and then allowed to incubate for a prolonged period (16 h), the cells become highly resistant to oxidant-mediated injury and to the accumulation of endothelial lipid peroxidation products. This protection is associated with the induction within 4 h of mRNAs for both heme oxygenase and ferritin. After 16 h heme oxygenase and ferritin have increased approximately 50-fold and 10-fold, respectively. Differential induction of these proteins determined that ferritin is probably the ultimate cytoprotectant. Ferritin inhibits oxidant-mediated cytolysis in direct relation to its intracellular concentration. Apoferritin, when added to cultured endothelial cells, is taken up in a dose-responsive manner and appears as cytoplasmic granules by immunofluorescence; in a similar dose-responsive manner, added apoferritin protects endothelial cells from oxidant-mediated cytolysis. Conversely, a site-directed mutant of ferritin (heavy chain Glu62----Lys; His65-- -Gly) which lacks ferroxidase activity and is deficient in iron sequestering capacity, is completely ineffectual as a cytoprotectant. We conclude that endothelium and perhaps other cell types may be protected from oxidant damage through the iron sequestrant, ferritin. PMID- 1517246 TI - The relationship between protein synthesis and heat shock proteins levels in rabbit reticulocyte lysates. AB - Besides heme deficiency, protein synthesis in rabbit reticulocyte lysates becomes inhibited upon exposure to a variety of agents that mimic conditions which induce the heat shock response in cells. This inhibition has been demonstrated to be due primarily to the activation of the heme-regulated eIF-2 alpha kinase (HRI) which causes an arrest in the initiation of translation. In this report, the sensitivity of protein synthesis in hemin-supplemented lysates to inhibition by Hg2+, GSSG, methylene blue, and heat shock was examined in six different reticulocyte lysate preparations. The extent to which translation was inhibited in response to Hg2+, GSSG, methylene blue, and heat shock correlated inversely with the relative levels of the 70-kDa heat shock proteins (hsp 70) and a 56-kDa protein (p56) present in the lysates determined by Western blotting. The ability of hemin to restore protein synthesis upon addition to heme-deficient lysates was also examined. While the restoration of protein synthesis correlated roughly with the levels of hsp 90 present, the results also suggest that the heme regulation of HRI probably involves the interaction of HRI with several factors present in the lysate besides hsp 90. A comparison of two lysate preparations, which had a 2 fold difference in their protein synthesis rates, indicated that the slower translational rate of the one lysate could be accounted for by its low level of constitutive eIF-2 alpha phosphorylation, with its accompanying decrease in the eIF-2B activity and lower level of polyribosome loading. The present study supports the notion that the previously demonstrated interaction of HRI with hsp 90, hsp 70, and p56 in reticulocyte lysates may play a direct role in regulating HRI activation or activity. We hypothesize that the competition of denatured protein and HRI for the binding of hsp 70 may be a molecular signal that triggers the activation of HRI in reticulocyte lysates in response to stress. Possible functions for p56 in the regulation of HRI activity are also discussed. PMID- 1517247 TI - Interaction of Xenopus TFIIIC with the TFIIIA.5 S RNA gene complex. AB - The general transcription factor TFIIIC is necessary for transcription initiation by RNA polymerase III. TFIIIC binds predominantly to the B-Block promoter element, which is present in tRNA genes, several viral RNA genes and repetitive DNA elements, and to the TFIIIA.DNA complex on 5 S RNA genes. Here we report a characterization of Xenopus laevis TFIIIC and its interaction with the TFIIIA.5 S RNA gene complex. A polypeptide with apparent molecular mass of 85 kDa was specifically cross-linked to a B-Block oligonucleotide by UV light. This polypeptide was present in the partially purified TFIIIC fraction and in a complex with a B-Block double-stranded oligonucleotide isolated by nondenaturing gel electrophoresis. TFIIIC.TFIIIA.DNA gel mobility shift complexes were obtained using B-Block DNA affinity-purified TFIIIC and buffer conditions employing low Mg2+ (1 mM) and high dithiothreitol (7 mM) concentrations. Three TFIIIC.TFIIIA.5 S RNA gene complexes were observed by gel mobility shift analysis. One of these complexes was resistant to dissociation by the addition of competing DNA, but the formation of all three complexes was prevented by the inclusion of excess specific competitor DNA in the initial binding reactions. The apparent affinity of TFIIIC for the TFIIIA.5 S DNA complex was 5-fold higher for the somatic-type 5 S RNA gene than for the oocyte-type 5 S RNA gene. Mutations near the 5' boundary of the TFIIIA binding site alter the DNase I footprint of the TFIIIA.DNA complex and reduce the affinity of TFIIIA-mutant 5 S gene complexes for TFIIIC. Differences in TFIIIC affinity for the two classes of 5 S RNA genes may play a role in the developmental regulation of these gene families. PMID- 1517248 TI - The heparin-binding domain of extracellular superoxide dismutase C and formation of variants with reduced heparin affinity. AB - A fundamental property of the secretory tetrameric extracellular superoxide dismutase (EC-SOD) is its affinity for heparin and analogues, in vivo, mediating attachment to heparan sulfate proteoglycans located on cell surfaces and in the connective tissue matrix. EC-SOD is in vivo heterogeneous with regard to heparin affinity and can be divided into subclasses; A which lacks heparin affinity, B with intermediate affinity, and C with strong heparin affinity. The EC-SOD C subunits contain 222 amino acids and among the last 20 carboxyl-terminal amino acids, 10 are positively charged and six of these are located in a cluster in positions 210-215. To analyze if this local accumulation of basic amino acids is responsible for heparin binding we produced three series of recombinant EC-SOD (rEC-SOD) variants, six containing amino acid exchanges in the carboxyl-terminal end, four with truncations, and two with both truncations and substitutions. Exchange of positively or negatively charged amino acids on the carboxyl-terminal side of the cluster results in only minor modifications in heparin affinity, whereas substitution of three of the amino acids in the cluster abrogates the heparin binding. Insertions of stop codons at different positions resulted in either C or A but not B class EC-SOD. In an attempt to produce EC-SODs with intermediate heparin affinities, plasmids defining C and A class EC-SOD were cotransfected into Chinese hamster ovary cells. In addition to the parental A and C class EC-SOD forms, two variants with intermediate heparin affinities were formed. Coincubation of EC-SOD C and A resulted in the appearance of one heterotetramer with intermediate affinity for heparin. We conclude that the cluster of six basic amino acids forms the essential part of the heparin-binding domain and that the composition of the four subunits in the EC-SOD tetramer determines the affinity for heparin. This domain is different from heparin binding domains of other proteins, and its localization allows the distribution of EC-SOD in vivo to be regulated by proteolytic processing. PMID- 1517249 TI - Amyloidogenicity of beta A4 and beta A4-bearing amyloid protein precursor fragments by metal-catalyzed oxidation. AB - Previously we have shown that the COOH-terminal 100 residues (A4CT) of the amyloid protein precursor (APP), which carry the sequence of the amyloid beta A4 protein of Alzheimer's disease at N-terminal position, form highly insoluble aggregates if expressed in the rabbit reticulocyte lysate and analyzed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (Dyrks, T., Weidemann, A., Multhaup, G., Salbaum, J.M., Lemaire, H.-G., Kang, J., Muller-Hill, B., Masters, C. L., and Beyreuther, K. (1988) EMBO J. 7, 949-957). Here we report that aggregation of this COOH-terminal APP fragment A4CT and also of beta A4 itself depends on additional factors. In contrast to the reticulocyte expression system, expression of A4CT and beta A4 in the wheat germ expression system resulted in only monomeric forms. We have identified the factors which are capable of transforming both soluble A4CT and beta A4 into insoluble and aggregating molecules. Monomeric A4CT or beta A4 expressed in the wheat germ lysate could be transformed into aggregating molecules by the addition of metal-catalyzed oxidation systems. The addition of radical scavengers such as ascorbic acid, trolox, and amino acids prevented the aggregation process induced by the radical initiators. Thus, the aggregation of amyloidogenic APP fragments if analyzed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis requires amino acid oxidation and protein cross-linking induced by radical generation systems. PMID- 1517250 TI - The capsular polysaccharide of Bacteroides fragilis comprises two ionically linked polysaccharides. AB - Recently, we have shown that the capsular polysaccharide of Bacteroides fragilis NCTC 9343 is composed of an aggregate of two discrete large molecular weight polysaccharides (designated polysaccharides A and B). Following disaggregation of this capsular complex by very mild acid treatment, high resolution NMR spectroscopy demonstrated that polysaccharides A and B consist of highly charged repeating unit structures with unusual substituent groups (Baumann, H., Tzianabos, A. O., Brisson, J.-R., Kasper, D.L., and Jennings, H.J. (1992) Biochemistry 31, 4081-4089). Presently, we report that the capsular polysaccharide of B. fragilis represents a complex structure that is formed as a result of ionic interactions between polysaccharides A and B. Electron microscopy of immunogold-labeled organisms (with monoclonal antibodies specific for polysaccharides A and B) demonstrated that the two polysaccharides are co expressed on the cell surface of B. fragilis. We have shown that the purified capsule complex is made up exclusively of polysaccharide A and polysaccharide B (no other macromolecular structure was detected) in a 1:3.3 ratio and that disaggregation of this complex into the native forms of the constituent polysaccharides could be accomplished by preparative isoelectric focusing. Structural analyses of the native polysaccharides A and B showed that they possessed the same repeating unit structures as the respective acid-derived polysaccharides. The ionic nature of the linkage between polysaccharides A and B was demonstrated by reassociation of the native polysaccharides to form an aggregated polymer comparable to the original complex. The distinctive composition of this macromolecule may provide a rationale for the unusual biologic properties associated with the B. fragilis capsular polysaccharide. PMID- 1517252 TI - Ice friction during speed skating. AB - During speed skating, the external power output delivered by the athlete is predominantly used to overcome the air and ice frictional forces. Special skates were developed and used to measure the ice frictional forces during actual speed skating. The mean coefficients of friction for the straights and curves were, respectively, 0.0046 and 0.0059. The minimum value of the coefficient of ice friction was measured at an ice surface temperature of about -7 degrees C. It was found that the coefficient of friction increases with increasing speed. In the literature, it is suggested that the relatively low friction in skating results from a thin film of liquid water on the ice surface. Theories about the presence of water between the rubbing surfaces are focused on the formation of water by pressure-melting, melting due to frictional heating and on the 'liquid-like' properties of the ice surface. From our measurements and calculations, it is concluded that the liquid-like surface properties of ice seem to be a reasonable explanation for the low friction during speed skating. PMID- 1517251 TI - Parathyroid hormone-related protein. Evidence for secretion of a novel mid-region fragment by three different cell types. AB - The cDNA-predicted amino acid sequence of parathyroid hormone-related protein (PTHrP) contains multiple basic amino acid motifs, suggesting that PTHrP undergoes extensive post-translational processing prior to secretion. The secretory forms of the peptide are currently unknown. To identify these secretory forms, medium was harvested from three cell types: human renal carcinoma (SKRC-1) cells, human keratinocytes, and rat insulinoma cells stably transfected with the cDNA for PTHrP(1-141) (RIN-141 cells). Amino-terminal species were immunopurified using an anti-PTHrP(1-36) column, and mid-region species using an anti-PTHrP(37 74) column. PTHrP peptides in medium and in cell extracts were further resolved by reverse phase high performance liquid chromatography (RP-HPLC) and identified using region-specific immunoassays. SKRC-1 and RIN-141 cells secreted three distinct amino-terminal species and a novel, non-amino-terminal, mid-region fragment. Sequence and sodium dodecyl sulfate-polyacrylamide gel electrophoresis analysis indicated that the RIN-141 cell mid-region fragment begins at amino acid 38 of the cDNA-predicted sequence and is approximately 70 amino acids in length. Comparison of RP-HPLC elution patterns suggests that SKRC-1 cells and keratinocytes secrete a similar or identical mid-region fragment. Immunofluorescence studies revealed a Golgi pattern for the amino-terminal species and a secretory granule pattern for the mid-region fragment. These studies indicate that 1) multiple PTHrP species are secreted, including a novel mid-region fragment; 2) Arg37 serves as a cleavage site in at least three cell types; 3) PTHrP(1-36) is likely to be an authentic secretory form of PTHrP; and 4) the mid-region fragment appears to be packaged into secretory granules. The marked interspecies conservation of this mid-region PTHrP suggests that it will have important biological functions. PMID- 1517253 TI - A power equation for the sprint in speed skating. AB - An analysis of the start of the 500 m speed skating races during the 1988 Olympic Winter Games showed a remarkably high correlation between the acceleration of the skater in the first second of the sprint and the final time (r = -0.75). In this study a power equation is used to explain this high coefficient of correlation. The performance in speed skating is determined by the capability of external power production by the speed skater. This power is necessary to overcome the air and ice friction and to increase the kinetic energy of the skater. Numerical values of the power dissipated to air and ice friction, both dependent on speed, are obtained from ice friction and wind tunnel experiments. Using aerobic and anaerobic power production as measured during supra maximal bicycle tests of international-level speed skaters, a model of the kinetics of power production is obtained. Simulation of power production and power dissipation yields values of speed and acceleration and, finally, the performance time of the sprint during speed skating. The mean split time at 100 m and the final time at 500 m in these races, derived from simulation, were 10.57 s (+/- 0.31) and 37.82 s (+/- 0.96), respectively. The coefficient of correlation between the simulated 500 m times and the actual 500 m times was 0.90. From the results of this study it can be concluded that the distribution of the available anaerobic energy is an important factor in the short lasting events. For the same amount of anaerobic energy the better sprinters appear to be able to liberate considerably more energy at the onset of the race than skaters of lower performance level. PMID- 1517254 TI - A theoretical model for the noninvasive assessment of the transmitral pressure flow relation. AB - The purpose of this paper is to formulate from the equations of fluid mechanics an equation which describes the transmitral pressure-flow relationship. According to the linear momentum equation applied to the atrioventricular coupling, the left-atrium-left-ventricle pressure difference (Pa-Pv) can be written as Pa-P v = A delta v/delta t + B v 2 + C v, where v is the transmitral blood velocity and A, B, and C are variables related to the geometry of the atrium, ventricle and mitral orifice, respectively. Based on this theory, Pa-Pv is calculated noninvasively in a patient with a nonobstructive mitral valve. Mitral flow and cardiac dimensions recorded by Doppler echocardiography are digitized and analyzed. Calculation shows that Pa-Pv reaches its peak value at the time of flow peak acceleration and has already considerably decreased at the time of peak velocity. The time course of calculated Pa-Pv is in close agreement with the published experimental catherization data. Numerical computation of early diastolic left atrium and left ventricle pressure curves based on the experimental data of others for the time constant of left ventricular relaxation, left atrial and ventricular chambers stiffness constants, combined with sine waveform-simulated mitral flow, verifies the time course and the magnitude of Pa Pv as predicted from flow equations. This paper provides a theoretical method for the noninvasive assessment of the transmitral pressure-flow relationship using ultrasound technique and might help to achieve a better understanding of the diastolic function as assessed by Doppler echocardiography. PMID- 1517255 TI - Curvature characteristics and congruence of the thumb carpometacarpal joint: differences between female and male joints. AB - Three-dimensional geometric models of the articular surfaces of the thumb carpometacarpal (CMC) joint were constructed using precise data obtained from stereophotogrammetry (SPG). It was demonstrated that by using a least-squares surface-fitting technique, the SPG data on the surface can accurately be described by a single parametric biquintic spline function. From this mathematical description, curvature maps of the surfaces were calculated for 13 CMC joints (eight females, average 64 yr old, five males, average 70 yr old). The surface geometry of each joint was analyzed, comparisons were made between trapezial and metacarpal surfaces of the joint and differences determined between males and females. With regard to joint surface areas, the female trapezium is significantly smaller than that of the metacarpal. The shape of the female trapezial surface is also fundamentally different from that of males. No gender related difference exists regarding the shape of the metacarpal surface. Congruence of the two opposing articular surfaces was defined by their relative principal curvatures. From these definitions, congruence in the radioulnar and dorsovolar anatomic directions, as well as the global congruence of the joint, were calculated. Most CMC joints were found to be more congruent along the radioulnar direction than the dorsovolar direction and, globally, female joints were found to be less congruent than male joints. The concept of joint congruence has played a central role in a number of hypotheses relating to the etiology of CMC joint osteoarthritis (OA), although conflicting hypotheses do exist. The precise quantitative findings of this study may lead to an improved understanding of CMC joint OA, and perhaps explain its prevalence in the female population over 55. PMID- 1517256 TI - Prediction of the loading along the leg during snow skiing. AB - The complete force and moment of each cross section of the leg between the ski boot top and the knee during normal skiing were predicted from measurements of the force and moment under the toe and heel of the boot and the flexion of the ankle. The force and moment components predicted at the base of the boot were significantly different from those predicted at sites of potential injury at the boot top and the knee. The maximum torsional and maximum varus-valgus moments predicted at the knee over all subjects tested were 70 Nm and 149 Nm, which are within the estimated range of the ultimate strength of the knee without support from contracted muscles crossing the knee. Regression analyses were used to find the force components at the base of the boot that best predict the bending and torsional moments at the boot top and knee. The torsional moments at the boot top and knee are best predicted by the medial-lateral force at the toe. The varus valgus moment at the boot top and knee are best predicted by the resultant medial lateral force component at the base of the boot. The set of best predictors of the anterior-posterior bending moments at the boot top and knee includes the vertical force at the toe, the vertical force at the heel and the component of the total vertical force directed perpendicular to the leg. PMID- 1517257 TI - A miniature piezoelectric polymer transducer for in vitro measurement of the dynamic contact stress distribution. AB - Previous studies of contact pressure measurement between articular surfaces have been mostly limited to static techniques. The purpose of our study was to develop a new dynamic technique for a direct measurement of the local contact stresses, and to apply the new method to an in vitro cadaver study of the patellofemoral joint pressures. The miniature transducer consists of a 2 mm diameter and 28 microns thick piece of piezoelectric polymer film sandwiched between two stainless steel electrodes of similar diameter. A water-resistant capsule consisting of Teflon film and Hysol epoxy was applied around the transducer. The transducer was 3 mm in diameter and 0.7 mm in thickness. A 3 mm well was made at six locations in the patella, corresponding to superior, middle, and inferior regions of both facets. Six transducers were cemented within each well, flush with the articular cartilage. The transducers were calibrated in situ before and after the experiment. The femur was rigidly fixed to the loading apparatus and the tibia was allowed to flex and extend through a 90 degrees range of motion using an Instron and a pulley system connected to the quadriceps tendon. Q angles of 0, 5, 10 and 15 degrees were established by adjusting the direction of the quadriceps tendon. Stresses ranging from 0.1-1.3 MPa were recorded at various locations. These values varied in flexion and extension. An overall decrease in these stresses was noted after tuberosity elevation up to 1.5 cm, following which increased values up to 1.8 MPa were recorded mostly in the superior section.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1517258 TI - In vivo tracking of the human patella. AB - The purpose of this study was to describe the dynamic, in vivo, three-dimensional tracking pattern of the patella for one normal male subject. Intracortical pins were inserted into the patella, tibia, and femur. The subject performed seated and squatting knee flexion/extension, and maximum voluntary quadriceps contractions. In addition, the vastus medialis oblique was subjected to maximal electrical stimulation. Motions of the markers attached to the intracortical pins were analyzed using an automated video system. Patellar and tibial motions were determined relative to a femoral reference system. While the tibia flexed 50 degrees from full extension (seated condition), the patella flexed 30.3 degrees, tilted laterally 10.3 degrees, and shifted laterally 8.6 mm. In general, these results show qualitative agreement with the data collected from cadaveric specimens [van Kampen and Huiskes, J. orthop. Res. 8, 372-382 (1990)]. The differences present may reflect different passive constraints to patellar motions, and different relative loading of the individual quadriceps components, in our study compared to the cadaveric study. Only small differences were found between patellar motions in the seated and squatting conditions. Differences in patellar displacements produced by (1) maximal electrical stimulation of the vastus medialis oblique, and (2) maximum voluntary quadriceps contraction, at 30 degrees knee flexion and full extension, may reflect the dominant influence of passive constraints, and the vastus lateralis, on normal patellar motions. Further in vivo study of patellar tracking seems warranted to evaluate surgical and conservative interventions for patellofemoral disorders. PMID- 1517259 TI - Periosteal and endosteal control of bone remodeling under torsional loading. AB - The shape changes that occur in the mid-diaphysis of a long bone due to adaptive remodeling induced by increasing or decreasing the axial and/or torsional loading of the bone are investigated using a simple model. In this model the mid diaphysis of a long bone is represented as a hollow thick-walled right-circular cylinder, and different optimal strategies for bone remodeling are considered. It is shown that if such a thick-walled right-circular cylinder capable of surface remodeling is subjected to an axial compressive load and a twisting torque, then the remodeling patterns depend on whether the periosteal surface or the endosteal surface controls the limits of the remodeling process. It is shown that the effect of increasing the torque is always opposite to the effect of increasing the compressive load. Thus, similar remodeling patterns are obtained by increasing one type of loading and decreasing the other. Aside from the restriction of idealized cylindrical geometry, the only assumptions made are that the bone tissue is linearly elastic and that there exists a finite range of remodeling equilibrium stresses. Only those loading situations which maintain the bone in remodeling equilibrium are considered in this work. It follows that the results presented are independent of the specific type of rule governing the temporal evolution of the bone shape, since any such rule applies only in situations where there is active remodeling and, hence, no remodeling equilibrium. PMID- 1517260 TI - Comment on "Variations of stiffness and strength along the human cervical spine". PMID- 1517261 TI - Hemiplegic gait: a kinematic analysis using walking speed as a basis. AB - The kinematics of treadmill ambulation of stroke patients (N = 9) and healthy subjects (N = 4) was studied at a wide range of different velocities (i.e. 0.25 1.5 m s-1), with a focus on the transverse rotations of the trunk. Video recordings revealed, for both stroke patients and healthy subjects, similar relations between walking speed and stride length as well as stride frequency. The phase difference between pelvic and thoracic rotations (i.e. trunk rotation) and the total range of trunk rotation were almost linearly related to the walking speed. Healthy subjects showed a marked increase in pelvic rotation from 1 to 1.5 m s-1. Using dimensional analysis in a comparison between stroke patients and healthy subjects, invariances in the coordination of gait were found for stride length, stride frequency, pelvic rotation, and trunk rotation. Constant relations were obtained between, on the one hand, dimensionless velocity and, on the other, dimensionless stride length as well as stride frequency. Transitions were found between the velocities 0.75 and 1 m s-1 for dimensionless pelvic rotation and trunk rotation, indicating that, from this velocity range onwards, pelvic swing lengthens the stride: rotations of pelvis, thorax and trunk become tightly coordinated. On the basis of the dimensionless stride length, stride frequency, pelvic rotation and trunk rotation, deficits in the gait of stroke patients could be quantified. It is concluded that walking speed is an important control parameter, which should be used as a basic variable in the evaluation of the gait of stroke patients. PMID- 1517262 TI - Influence of muscle geometry on shortening speed of fibre, aponeurosis and muscle. AB - The influence of muscle geometry on muscle shortening of the gastrocnemius medialis muscle (GM) of the rat was studied. Using cinematography, GM geometry was studied during isokinetic concentric activity at muscle lengths ranging from 85 to 105% of the optimum muscle length. The shortening speed of the distal fibre, the proximal aponeurosis and the muscle were determined, as well as the effect of rotation of the distal fibre and the proximal aponeurosis on the muscle speed of shortening. The results show that, due to the geometrical configuration, muscle shortening speed is not only determined by the speed of the fibre, but also to a large extent by the aponeurosis shortening speed. At optimum muscle length, the fibre and aponeurosis shortening speeds expressed relative to the muscle shortening speed amounted to 84% and 6%, respectively. At shorter muscle length, fibre speed relative to muscle speed decreased to values as low as 35%, whereas that of aponeurosis increased to values as high as 31%. Angular effects on the muscle speed of shortening can explain 10% of the muscle shortening speed at optimum muscle length and up to 34% of the muscle speed at shorter muscle length. In addition, a model was formulated to simulate the geometrical effects on muscle speed. This model, incorporating both fibre and aponeurosis length changes, contains a transfer function relating the shortening speeds of fibre and aponeurosis to muscle speed. The muscle shortening speed calculated using this transfer function demonstrated no significant differences with the speed measured experimentally. PMID- 1517263 TI - A transversely isotropic biphasic finite element model of the meniscus. AB - A finite element model of the meniscus is presented, based on an axisymmetric geometric approximation of the menisci and a biphasic description of the tissue as a mixture of solid and fluid components. The highly fibrous nature of the meniscal tissue is accounted for by using a fiber-reinforced, transversely isotropic description of the solid phase. This model is used to study the response of a meniscus resting on a perfectly lubricated tibial surface and subjected to distributed loads applied to the femoral surface, and to examine the effects of changes in loading conditions at the femoral and tibial interfaces. Quantities of interest include the stress, pressure and strain distributions at discrete times early in the meniscal response, and the flow of the fluid phase relative to the solid phase. Of particular interest are regions of large tensile strains which could lead to meniscal failures such as the bucket-handle tear. We show that all components of strain are positive in regions of the outer third of the meniscus, and that the maximum tensile strain perpendicular to the circumferentially arranged fibers (largest principal strain in the axisymmetric cross section) is positive throughout most of the cross section. Changing the partition of the load on the femoral surface and the permeability at the tibial surface changes the time-dependent response, but has little effect on the strain distributions at times of the order of 5 s considered in this study. The inclusion of a transversely isotropic, fibrous representation of the solid phases is shown to be essential to proper meniscal simulation. The results demonstrate the importance of the biphasic representation since the fluid phase is shown to carry a significant part of the applied load. PMID- 1517264 TI - Taper: an important feature of Y-bifurcations in porcine renal arteries and human cerebral arteries. AB - The geometry of arterial bifurcations has been shown to alter fluid flow and the propagation of both pressure and flow waves. Here we provide a more complete description of the renal artery bifurcation geometry and show that the geometry of the bifurcation is more complex than was believed previously. The objective of this study was to quantify changes in cross-sectional luminal area in systemic arterial bifurcations using the method developed by Macfarlane [Ph.D. thesis, University of Western Ontario, Ontario (1985)] to study the geometry of human cerebral bifurcations. Porcine renal arterial bifurcations from seven young (6-14 weeks) and six old (greater than 52 weeks) animals were pressure-fixed (P = 140 mmHg) for 3 h with 10% formalin. Bifurcations were embedded in a block of frozen latex paint. Serial sections were cut at 20 microns (+/- 0.01 microns) using a sledge microtome while the block face was scanned with a video camera and the images were stored on a videotape. The luminal area was measured digitally upon playback. Bifurcations from the two age groups changed in cross-sectional area not only at the flow divider but also along the so-called straight regions. Proximal linear increases in cross-sectional area were observed proximal to the apex of the bifurcation in both young and old vessels, while linear luminal area decreases were measured in the daughter branches of both young and old porcine renals. Taper was defined as the change in luminal area per unit length of parent and daughter branches, respectively.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1517265 TI - Accuracy assessment and control point configuration when using the DLT for photogrammetry. AB - The direct linear transformation (DLT) is a common technique used to calibrate cameras and subsequently reconstruct points filmed with two or more cameras in a three-dimensional object space. The assessment of the accuracy of this technique, and of the influence of the distribution of control points on accuracy were examined. It was concluded that to obtain a true estimation of reconstruction accuracy, an independent assessment criterion is required, and that the use of control points distributed around the outside, rather than within the space to be calibrated, is preferred. PMID- 1517266 TI - A simplified radiographic method for measuring bone-component motion in total knees. AB - Measurement of the relative motion between an implant and the surrounding bone over different time periods is valuable for assessing and comparing the component stability and predicting the potential future outcome. The RSA method, where small beads are implanted in the bone adjacent to the component, can measure implant-bone position to an accuracy of about 0.1 mm. However, the method involves special radiographic views and analytical software, not readily available. For purposes of component assessment on a more routine basis and for multi-centre trials, a method was developed where standard A-P and M-L radiographs were used. Computer software was written which estimated the out-of plane rotations of the component relative to the plane of the film, and then carried out corrections to enhance the accuracy of calculation of the bead heights relative to the component. The theoretical errors were shown to be less than 0.04 mm for the expected range of out-of-plane rotations. When radiographs of components in simulated bones were taken at a range of rotations, the 95% confidence limits for axial displacement were found to be less than +0.3 mm, and for rotation in the plane to be 0.6 degrees. This indicated that the method was useful for studying knee components where the sinkage could reach a range of 0.5 2 mm in a 2 year period. PMID- 1517267 TI - Velocity of ultrasound in active and passive cat medial gastrocnemius muscle. AB - The lengths and pinnation angles of muscle fibers in the medial gastrocnemius (MG) muscle have recently been measured in freely moving cats [Hoffer et al., Progr. Brain Res. 80, 75-85 (1989); Muscle Afferents and Spinal Control of Movement (1992)] using an ultrasound transit-time (USTT) technique. This method assumed that the velocity of ultrasound through intact muscles was constant, independent of fiber orientation, muscle activity, load, belly shape, or fiber movement. However, the velocity of ultrasound along and across the fibers has been reported to depend on the state of muscle activation in frog muscle experiments in vitro [Hatta et al., J. Physiol. 403, 193-209 (1988)]. In the present study, the assumption of constant velocity of ultrasound in the cat MG muscle was evaluated. In acute experiments, done in situ with intact blood supply, the USTT was measured along and across cat MG muscle fibers in the passive, reflexly activated and tetanically activated states, with and without changes in muscle fiber length, for situations that reproduced the length and force ranges normally used by cats during locomotion. The velocity of ultrasound was found to be independent of the state of activation or motion of the muscle, and independent of the direction of the measurement with respect to the fiber orientation, within a measurement uncertainty less than or equal to 0.2%. These results validate the use of the USTT technique for the measurement of intramuscular dimensions in freely moving animals. PMID- 1517268 TI - A noninvasive technique for in vivo measurement of joint torques of biarticular muscles. AB - The objective of this work was to develop a noninvasive method to measure the joint torques produced by biarticular muscles at two joints simultaneously. During intramuscular stimulation of the cat medial gastrocnemius (MG) muscle, torques at the ankle and knee joints were calculated from forces measured in two dimensions at the end point of the cat paw under isometric conditions. The method was verified by the known anatomical properties of cat MG muscle and the tibialis anterior (TA) muscle. The MG muscle was shown to produce a significant flexion torque at the knee, besides an extension torque at the ankle. This was in agreement with its anatomical arrangement. The TA muscle produced primarily an ankle flexion torque. The small knee torque, due to measurement errors, yielded an estimate of measurement accuracy of 3.0 +/- 2.1% (n = 52). The coupling ratio of the MG muscle, defined as T(ankle)/T(knee), varied significantly with both knee and ankle angles. The profile of MG mechanical coupling agreed qualitatively with changes in limb configuration. The method can be used to measure recruitment properties of electrically stimulated biarticular muscles, and may potentially be used to study the biomechanics of biarticular coupling. PMID- 1517269 TI - Characterizing bone strain distributions in vivo using three triple rosette strain gages. AB - Three triple-element rosette strain gages were attached to the equine third metacarpal midshaft to record site-specific strains engendered by locomotion. The distribution of strains acting upon the midshaft cross section were characterized using a combined beam theory and finite element model analysis that did not presume the manner by which the bone was inertially loaded. A medium-speed trot (3.6 ms-1) was chosen as a representative speed and gait, with normal and shear strains, and strain energy density (SED) distributions determined throughout the stance and subsequent swing phase. Importantly, the sites of maximum compression (-2400 mu epsilon), tension (810 mu epsilon), shear (1500 mu epsilon), and SED (54 kPa) were not located at any of the gage attachment sites, emphasizing that a minimum of three rosette gages are necessary to resolve the peaks and locations of functionally induced normal and shear strains. Considering the nonuniform strain distributions across the cortex, we conclude that the third metacarpal is subject to a complex loading milieu comprised of bending, axial compression, end shear, and torsion. As this complex manner of loading was consistent through the entire stance phase, it would appear that, at least during the trot, specific sites within the same cross section are subject to vastly different magnitudes of strain stimulus. PMID- 1517270 TI - Different methods to estimate total power and its components during lifting. AB - A more fundamental understanding about the act of manual lifting can be provided by the assessment of the total production of power and the power generated in joints. The present study is concerned with the validity of the estimations of these parameters. Four subjects lifted an 18.8 kg load while they were filmed and ground reaction forces were measured. The total generated power was calculated in three ways: (1) by summation of joint powers, (2) on the basis of the rate of change of the summed energy contents of human body segments, and (3) on the basis of the rate of change of the body energy estimated from ground reaction forces. The results were compared. Furthermore, at a segmental level the power supplied to or absorbed from a segment was compared to the rate of change of its energy content. The resulting instantaneous power curves from the three different methods showed a high level of agreement, which supports their validity. However, some minor discrepancies were observed. The major cause of the observed difference between the rate of change of the summed segmental energy contents and the summed joint powers was found at a segmental level. It was observed that segmental link lengths (i.e. distances between proximal and distal markers) changed during movement, which yielded discrepancies between the power flow to or from a segment and the rate of change of its energy content. PMID- 1517271 TI - Comments on 'a three-dimensional analysis of a bioprosthetic heart valve. PMID- 1517272 TI - Intermuscular coordination in a sprint push-off. AB - This study was designed to investigate the patterns of intermuscular coordination during a sprinting event. In previous research it was found that despite the indeterminacy problem of movement control, movements like vertical jumping, speed skating and cycling are performed in a stereotyped manner. It was hypothesized that this might be due to constraints associated with the transformation of joint rotations into the desired translation. The objective of the present study was to determine the extent to which the intermuscular coordination patterns during other movements also are performed in a stereotyped manner and, if that is true, whether this can be understood on the basis of such constraints. Seven elite sprint runners were instructed to execute an explosive sprinting dash. Ground reaction forces and cinematographic data were recorded for the second stance phase of the sprint. Simultaneously, electromyographic activity of nine leg muscles was recorded telemetrically. Linked-segment modeling was used to obtain net joint moments and net joint powers. Different athletes appeared to perform the sprint in a stereotyped manner. The muscle coordination pattern is characterized by a proximo to distal sequence in timing of the monoarticular muscles. When compared to the sequential pattern found in jumping, the biarticular hamstrings and rectus femoris muscles behave differently; in the sprint a more pronounced reciprocal activity between these muscles exists. The resulting movement pattern is characterized by a sequence of upper leg extension and plantar flexion. The observed sequence in timing of muscle activation patterns is aimed at solving the problems associated with the earlier identified geometrical and anatomical constraint. However, the coordination pattern cannot be fully understood on the basis of these constraints. A specific constraint is identified with respect to the direction of the ground reaction force, which explains the pronounced reciprocal activity of the biarticular hamstring and rectus femoris muscles. The intermuscular coordination pattern in the sprint can be seen as a compromise between the specific requirement of the sprint and the advantageous effect of a proximo to distal sequence as found previously for jumping. PMID- 1517273 TI - Predicted and observed shapes of human mandibular condyles. AB - A mathematical model based on linear programming was used to study the directions of the joint forces used to maintain the human jaw in three-dimensional static equilibrium when producing bite forces of 100 N to a maximum of 1000 N down the long axis of a central incisor, first premolar, first molar and third molar. Seven different versions of the model were studied. The two simplest versions minimized the total muscle tension and the total joint load, respectively. Assuming that the joint force direction must be normal to some part of the articular surface of the condyle, neither version produced directions consistent with the observed shapes of human condyles. The other five versions minimized different combinations of muscle tensions and joint loads. Two of these versions produced joint force directions compatible with the shapes of condyles. Both minimized total muscle tension plus the (vertical) joint load on the back of the condyle. The results suggest that joint mechanoreceptors (probably non directional) as well as muscle receptors contribute to the neuromuscular control of bite forces. Our results are consistent with some recent observations [Marshall and Tatton, Exp. Brain Res. 83, 137-150 (1990)] of the cat knee joint. PMID- 1517274 TI - The role of the shaft in the golf swing. AB - Current marketing of golf clubs places great emphasis on the importance of the correct choice of shaft in relation to the golfer. The design of shafts is based on a body of received wisdom for which there appears to be little in the way of hard evidence, either of a theoretical or experimental nature. In this paper the behaviour of the shaft in the golf swing is investigated using a suitable dynamic computer simulation and by making direct strain gauge measurements on the shaft during actual golf swings. The conclusion is, contrary to popular belief, that shaft bending flexibility plays a minor dynamic role in the golf swing and that the conventional tests associated with shaft specification are peculiarly inappropriate to the swing dynamics; other tests are proposed. A concomitant conclusion is that it should be difficult for the golfer to actually identify shaft flexibility. It is found that if golfers are asked to hit golf balls with sets of clubs having different shafts but identical swingweights the success rate in identifying the shaft is surprisingly low. PMID- 1517275 TI - Biomechanical consequences of callus development in Hoffmann, Wagner, Orthofix and Ilizarov external fixators. AB - A theoretical analysis by a finite elements model (FEM) of some external fixators (Hoffmann, Wagner, Orthofix and Ilizarov) was carried out. This study considered a logarithmic progress of callus elastic characteristics. A standard configuration of each fixator was defined where design and application characteristics were modified. A comparison among standard configurations and influence of every variation was made with regard to displacement and load transmission at the fracture site. An experimental evaluation of standard configurations was performed with a testing machine. After experimental validation of the theoretical model was achieved, an application of physiological loads which act on a fractured limb during normal gait was analysed. A minimal contribution from an external fixator to the total rigidity of the bone-callus fixator system was assessed when a callus showing minimum elastic characteristics had just been established. Insufficient rigidity from the fixation devices to assure an adequate immobilization during the early stages of fracture healing was verified. However, regardless of the external fixator, callus development was the overriding element for the rigidity of the fixator-bone system. PMID- 1517276 TI - Complete disappearance of metastatic abdominal tumors from gastric cancer after treatment with irsogladine maleate. AB - A 60-year-old woman with gastric cancer had undergone partial gastrectomy in September 1989. Pathological examination revealed a poorly differentiated adenocarcinoma of pT3pN3pM0 (not resected for cure), stage IV. Postoperative adjuvant therapy comprised 1-(tetrahydro-2-furanyl)-5-fluorouracil plus uracil and OK-432. On 11 August 1990, two forefinger-tip-sized tumors were palpated beneath the operation scar. They increase in size, the superior tumor reaching 4x3 cm, the inferior tumor 5x3 cm on 5 September. Then, on 17 September, the inferior tumor was resected but the superior tumor remained; the histological type was poorly differentiated adenocarcinoma. After the operation, from 20 September, she was given 4 mg irsogladine maleate orally every day. On 8 October, there was no increase in the size of the superior tumor. By 29 October, the superior tumor had disappeared and no further tumor appeared thereafter; the patient showed no sign of relapse. PMID- 1517277 TI - Effect of chemotherapy combined with caffeine for osteosarcoma. AB - Nine patients with osteosarcoma were treated by chemotherapy combined with caffeine and surgery. All primary tumors showed complete histological response to preoperative chemotherapy consisting of three intraarterial infusions of cisplatin and caffeine without/with doxorubicin and two systemic high-dose methotrexate combined with vincristine. Limb-salvage surgery was performed in eight patients with marginal procedure, which led to the preservation of good limb function. Below-knee amputation was done in one patient with calcaneal osteosarcoma. There has been neither local recurrence nor lung metastasis in seven patients with conventional osteosarcoma during a median follow-up period of 28 months. Lung metastases leading to death were observed in one patient with small-cell osteosarcoma despite complete destruction of the primary tumor by preoperative chemotherapy. Chemotherapy combined with caffeine administration deserves further extensive and large-scale study in osteosarcoma. PMID- 1517278 TI - Is bile or are pancreaticoduodenal secretions related to gastric carcinogenesis in rats with reflux through the pylorus? AB - Male Wistar rats were subjected to one of three types of operative reflux procedure that allowed part or all of the duodenal contents to flow back into the stomach through the pylorus, thus producing models of bile reflux alone, pancreaticoduodenal reflux alone, and combined reflux. All surviving animals were killed 50 weeks after surgery and the development of gastric cancer was assessed. No cancer was seen in 16 animals with pancreaticoduodenal reflux or in 32 control animals with gastrotomy, whereas 2/8 animals with bile reflux and 11/29 animals with combined reflux had gastric carcinoma. Compared with the control group, the incidence of carcinoma in animals with bile or combined reflux was significantly higher (P less than 0.05 and P less than 0.01 respectively). All carcinomas developed in the antral area near the pylorus. Adenomas were observed only in the groups of animals developing carcinoma and occurred in the same region of the stomach. These results suggest that bile, and not pancreaticoduodenal secretions, is the component of the duodenal contents responsible for the development of gastric carcinoma. PMID- 1517279 TI - Molecular-genetic analysis of ocular adnexal benign lymphoid hyperplasias by a two-step polymerase-chain-reaction. AB - Twelve biopsied ocular adnexal benign lymphoid hyperplasias (OABLH) satisfying benign histological criteria were investigated for clonal immunoglobulin (Ig) heavy-chain gene rearrangement by means of a two-step polymerase chain reaction (PCR) method using formalin-fixed and paraffin-embedded tissue. Of the 12, 4 (33%) demonstrated clear single bands of the rearranged gene for the Ig heavy chain, of between 100 and 150 base pairs. The selected cases were all free of malignant lymphoma and all of the lesions were small (2 x 2-22 x 6 mm; median 4.5 x 3 mm). Histopathological and cytological features were not essentially different between monoclonal and non-monoclonal examples. Immunohistochemistry was of little benefit in separating the two. It is concluded that OABLH demonstrating a benign clinical course frequently contain monoclonal B cell populations suggesting a continuous progressive spectrum of lesions in B cell neoplasia. In addition, the significance of molecular-genetic analysis for OABLH and the utility of the two-step PCR method should be emphasized. PMID- 1517280 TI - Induction/repair of strand breakage in mature and nascent DNA of cultured Chinese hamster ovary cells exposed to hydrogen peroxide. AB - Treatment of cultured mammalian cells with hydrogen peroxide results in the production of extensive DNA damage. Strand breakage was produced at the level of either nascent or mature DNA and the former target appeared slightly more resistant than the latter. Although inhibitors of the enzyme poly(ADP-ribose) polymerase similarly retarded the repair of such lesions, removal of DNA strand breaks was much slower for the newly synthesized DNA as compared to mature DNA. PMID- 1517281 TI - Hyaluronidase enhances the activity of adriamycin in breast cancer models in vitro and in vivo. AB - The effect of hyaluronidase and a combination of hyaluronidase with Adriamycin was investigated on several breast cancer models in vitro and in vivo. In vitro enzyme treatment (using concentrations up to 80,000 IU/1) of murine (MXT-, MXT +/ , and MXT+) and human (MCF-7, ZR-75-1 and T-47-D) breast cancer cell lines did not inhibit tumour cell proliferation (measured by a kinetic crystal violet assay) in either case. Although high-dose hyaluronidase (1.2 x 10(6) IU/kg) was ineffective, when administered peritumourally to the MXT M3.2 mammary carcinoma of the B6D2F1 mouse, it is remarkable that five "megadoses" were excellently tolerated. However, the antineoplastic activity of Adriamycin against the oestrogen-receptor-positive variant of the MXT tumour was significantly enhanced by combination with concentrations of hyaluronidase that were inactive per se, both in vitro and in vivo. Interestingly, the enhancement of the in vivo antitumour activity was not compromised by toxic side-effects. PMID- 1517282 TI - Prognostic factors in WHO grade 2 transitional-cell bladder cancer (TCC); a novel two-grade classification system for TCC based on mitotic index. AB - A retrospective histological analysis has been carried out on 537 cases of transitional-cell bladder carcinoma, followed-up over a period of 9 years. In the first part of the study WHO grade 2 tumours were analysed and a number of independent factors predictive for survival identified. In a multivariate analysis the T category and M/V index (number of mitotic figures/mm2 neoplastic epithelium) were the most important prognostic factors. In a subsequent analysis of the whole series of 537 cases, overall the M/V index was not as important in predicting survival as the stage of the tumour. However, in superficial tumours (Ta-T1) subsequent analysis showed that the M/V index alone could be used to predict survival. PMID- 1517283 TI - Tobacco-related cancer in relation to prevalence of drinking and smoking in eastern Austria. AB - Eastern Austrian regional mortality patterns of oral cancer (oral cavity, pharynx and larynx) and oesophageal, lung and urinary bladder cancer were compared to smoker rates and to liver cirrhosis mortality by type of residence: Vienna (1.7 x 10(6) inhabitants), middle towns (50,000-100,000 and 10,000-50,000 inhabitants), small towns (2000-10,000 inhabitants) and rural areas categorized by agrarian quota less than or equal to 10%, 10%-20% and greater than 20%. The study area (Vienna, Lower Austria and Burgenland) covers 23,600 km2 with 3.23 x 10(6) inhabitants. In men, liver cirrhosis correlated negatively with smoker rates (r = 0.74, P = 0.1). Deaths from oral cancer and oesophageal cancer correlated significantly with deaths from liver cirrhosis (r = 0.81, P = 0.03; r = 0.78, P = 0.04, respectively) but not with smoker rates; lung cancer and bladder cancer correlated significantly with smoker rates (r = 0.91, P = 0.01; r0.83, P = 0.04, respectively), but not with liver cirrhosis. In women, similar urban-rural gradients for all parameters resulted in a positive correlation between liver cirrhosis and smoker rates (r = 0.59, P = 0.22) and a significant correlation of lung cancer with liver cirrhosis (r = 0.75, P = 0.05). Oral cancer correlated significantly with liver cirrhosis (r = 0.83, P = 0.02), but not with smoker rates; lung cancer correlated more significantly with smoker rates (r = 0.92, P = 0.01) than with liver cirrhosis; bladder cancer correlated positively with smoker rates (r = 0.70, P = 0.12). Geographical distribution of oral and oesophageal cancer in Eastern Austria seems thus to be highly subject to the prevalence of heavy drinking. Sociocultural influences upon the occurrence of these cancers seem to be mediated through drinking habits rather than through smoking habits alone. PMID- 1517284 TI - Evaluation of tissue polypeptide antigen serum levels for monitoring disease activity during chemotherapy in patients with transitional carcinoma of the urinary tract. AB - In 28 patients with transitional carcinoma of the urinary tract, all treated with chemotherapy, serial measurements of serum tissue polypeptide antigen (TPA) were performed and correlated to clinical evaluations of response. At the start of chemotherapy elevated levels of TPA were found in 4 out of 14 patients with T2 4NO-2MO tumours and in 7 out of 14 patients with distant metastases. In most patients with elevated TPA levels who responded to chemotherapy, TPA levels rapidly returned to normal. False positive elevations of TPA were observed in 2 patients. It is concluded that serial measurement of TPA for monitoring disease activity has limited value because of the low sensitivity of TPA, especially for patients with early-stage cancer, and because of the occurrence of false positive results. PMID- 1517285 TI - Determination of phospholipid fatty acid and triacylglycerol composition of rat caecal mucosa. AB - The lipid composition of rat caecal mucosa, including the fatty acid composition of phospholipids and triacylglycerols, has been examined by capillary gas chromatography. Thirty-seven peaks were resolved, ranging in chain length from 12 to 24 carbon atoms. Preliminary identification of fatty acids by comparison with authentic standards was confirmed by gas chromatography-mass spectrometry using electron-impact ionization. The neutral and polar components were examined. Fatty acid methyl esters were quantified in absolute amounts with respect to the percentage of total phospholipid and triacylglycerols. The results show significantly higher levels of 16:0, 18:0, 18:1(n-9), 18:1(n-7), 18:2(n-6) and 20:4(n-6) in phospholipids, and higher levels of 16:0, 18:1(n-9) and 18:2(n-6) in triacylglycerols. On the other hand, analysis of caecal triacylglycerols revealed sn-glycerol-palmitate-oleate-palmitate, sn-glycerol-palmitate-linoleate-palmitate and sn-glycerol-palmitate-linoleate-oleate as major components. PMID- 1517286 TI - Determination of pentoxifylline and its metabolites in human plasma by high performance liquid chromatography with solid-phase extraction. AB - A simple and reliable method for the determination of pentoxifylline and its main metabolites in human plasma has been developed using high-performance liquid chromatography. After selective solid-phase extraction, pentoxifylline, its metabolites and an internal standard, 7-(2'-chloroethyl)theophylline, were separated on a 5-micron LiChrospher 100 RP-18 column using water-dioxan acetonitrile (87:6.5:6.5, v/v/v) acidified with acetic acid (0.5%, v/v) as the mobile phase. The analytes were detected at 275 nm. The lowest detectable concentration for all analytes was 25 ng/ml; the recovery was 85%. The assay has been successfully applied to analysis of these compounds in human plasma after administration of an oral dose of 400 mg of pentoxifylline to healthy volunteers. PMID- 1517287 TI - Two-dimensional high-performance liquid chromatographic method to assay p hydroxyphenylphenylhydantoin enantiomers in biological fluids and stereoselectivity of enzyme induction in phenytoin metabolism. AB - A two-dimensional high-performance liquid chromatographic method was developed to assay the enantiomers of a major phenytoin metabolite, p hydroxyphenylphenylhydantoin (p-HPPH). Racemic p-HPPH was first separated from phenytoin and other interfering peaks by a reversed-phase column and monitored by an ultraviolet detector. At the retention time of p-HPPH, the racemic p-HPPH peak was automatically transferred to a chiral ligand-exchange column to separate R-p HPPH and S-p-HPPH by a time-programmed column-switching valve. The ratio of enantiomers was measured by a second ultraviolet detector. The method can be used to assay R- and S-p-HPPH enantiomers with reasonable sensitivity and reproducibility. By using this method, the stereoselectivity of enzyme induction and inhibition of phenytoin metabolism was investigated. Male rats were treated with phenobarbital, 3-methylcholanthrene, acetone, Aroclor 1254, pregnenolone-16 alpha-carbonitrile, dexamethasone and isosafrole. Microsomes were prepared from the rat liver and phenytoin hydroxylation was measured. Pretreatment with phenobarbital, pregnenolone-16 alpha-carbonitrile or acetone induced phenytoin metabolism non-stereoselectively. Pretreatment with dexamethasone decreased R-p HPPH formation without affecting the formation of S-p-HPPH. Liver microsomes from female rats showed a higher S-p-HPPH formation, whereas R-p-HPPH formation remained the same. Various inhibitors were added to inhibit phenytoin metabolism by control microsomes. Sulphaphenazole, ketoconazole, 4,4-di(p methoxyphenyl)hydantoin, cimetidine and diazepam inhibited the formation of R- and S-p-HPPH. Quinidine, tolbutamide and mephenytoin showed no significant inhibitory activity. None of these inhibitors showed stereoselectivity. PMID- 1517288 TI - Determination of manidipine enantiomers in human serum using chiral chromatography and column-switching liquid chromatography. AB - A stereoselective and highly sensitive method using chiral chromatography and successive column-switching liquid chromatography is described for the determination of manidipine enantiomers in human serum. A human serum sample obtained after ingestion of manidipine was extracted twice with a mixture of n hexane-diethyl ether under alkaline conditions. The enantiomers in the extract were separated on a chiral stationary phase column (Chiralcel OJ), and the effluents containing the respective enantiomers were collected. Each fraction was then analysed by column-switching liquid chromatography. The proposed stereoselective method offered high sensitivity: detection limits for both isomers were 0.2 ng/ml in human serum, both at a signal-to-noise ratio of 3. The method is suitable for the pharmacokinetic studies of manidipine enantiomers. PMID- 1517289 TI - Determination of baicalin and baicalein in rat plasma by high-performance liquid chromatography with electrochemical detection. AB - A rapid and sensitive method, using electrochemical detection, has been developed for the determination of baicalin and baicalein, the flavonoid of Scutellariae radix, in rat plasma. Following separation by high-performance liquid chromatography, baicalin and baicalein were oxidized at a glassy carbon electrode to permit selective electrochemical detection. Absolute detection limits were found to be 5 ng/ml from 50 microliters of plasma for baicalin and 2 ng/ml from 100 microliters of plasma for baicalein. The resulting assays were suitable for pharmacokinetic studies of baicalin and baicalein in rats. PMID- 1517290 TI - Combined thin-layer chromatography-photography-densitometry for the quantification of ifosfamide and its principal metabolites in urine, cerebrospinal fluid and plasma. AB - A method has been devised for the determination of the anticancer drug ifosfamide and its principal metabolites in urine, plasma and cerebrospinal fluid (CSF). The urine and CSF samples are absorbed onto Amberlite XAD-2 eluting the compounds of interest with methanol. Plasma is deproteinated using cold acetonitrile and centrifuged to yield a clear supernatant. The eluate and supernatant are analyzed by thin-layer chromatography, with spot visualization using 4-(4 nitrobenzyl)pyridine. The plates are photographed for subsequent densitometeric analysis. The intra-assay coefficient of variation for each compound in both urine and plasma was less than 10% and the lower limit of detection was 1 microgram/ml. The method provides a means of determining the full spectrum of metabolic products of ifosfamide in patients and will allow detailed investigation of variability in metabolism and pharmacokinetics of this drug. PMID- 1517291 TI - In vivo transformation of arachidonic acid into 12-hydroxy-5,8,10,14 eicosatetraenoic acid by human nasal mucosa. AB - A method for the determination of 12-hydroxy-5,8,10,14-eicosatetraenoic acid (12 HETE) by gas chromatography-mass spectrometry (GC-MS) in samples obtained from healthy subjects by nasal lavage is presented. HETEs were extracted from samples obtained by nasal lavage using C18 solid-phase cartridges. The purification of 12 HETE and 5-HETE was carried out in two consecutive steps of purification by reversed-phase high-performance liquid chromatography. Methylated and trimethylsilylated fractions were separated by GC-MS with electron-impact ionization. The production of 12-HETE by human nasal mucosa was confirmed by GC MS. PMID- 1517292 TI - Determination of D- and L-amino acids in mouse kidney by high-performance liquid chromatography. AB - A method for the enantiomeric analysis of amino acids of mammalian tissues is described. An excellent resolution of D- and L-enantiomers of common protein amino acids was achieved by employing a combination of thin-layer chromatography and high-performance liquid chromatography. D-Enantiomers and L-enantiomers of glutamate, aspartate, glutamine, asparagine, serine, threonine, alanine, proline, tyrosine, valine, methionine, isoleucine, leucine, phenylalanine and histidine, as well as glycine were derivatized with 1-fluoro-2,4-dinitrophenyl-5-L-alanine amide. The amino acid diastereomers were separated by two-dimensional thin-layer chromatography. Each amino acid diastereomer was then analysed by reversed-phase high-performance liquid chromatography for the resolution of D- and L enantiomers. Very sharp peaks were obtained using a conventional octadecylsilyl bonded column, and the possibility of analysing these amino acids (except tyrosine and histidine) in subnanomole amounts was indicated. The method was used to demonstrate the presence of D-enantiomers of alanine, proline and serine in mouse kidney. PMID- 1517293 TI - Simultaneous determination of allantoin and oxypurines in biological fluids by high-performance liquid chromatography. AB - A high-performance liquid chromatographic method is described for the separation and quantification of allantoin and oxypurines in plasma and urine samples. Urine was analyzed directly and plasma after acid deproteinisation with perchloric acid. Separation and quantification of purine derivatives was achieved using two Spherisorb ODS-5 column (250 mm x 4.6 mm I.D.) connected in series together with a NH4H2PO4-NH4H2PO4-acetonitrile (80:20) gradient and monitoring the effluent at 205 nm. The average recoveries of standard compounds added to urine and plasma samples were 96 and 97%, respectively, using allopurinol as internal standard. The within-day variability was less than 7% and the day-to-day coefficient of variation less than 11% indicating a good precision of the method. PMID- 1517294 TI - Analysis of meconium for cocaine in neonates. AB - A solid-phase extraction method was developed for the extraction of first-day meconium samples from premature infants of cocaine-dependent mothers. Extracts were analysed by high-performance liquid chromatography and gas chromatography mass spectrometry for cocaine and its metabolites. Control stools showed no drug. Meconium from cocaine-dependent mothers showed cocaine in the range 0.1-0.78 micrograms/g. Benzoylecgonine, ecgonine and ecognine methyl ester were not present in the samples, which suggests that the metabolism of cocaine in the premature neonate is limited. PMID- 1517295 TI - Simple, rapid and selective method using high-performance liquid chromatography for the determination of bretylium in plasma. AB - A high-performance liquid chromatographic method with ultraviolet detection has been developed for the determination of bretylium in plasma. Following a single step solid-phase extraction procedure, bretylium is selectively isolated and well recovered from plasma. The assay sensitivity is 0.156 micrograms/ml from 250 microliters plasma samples and its linearity was assessed up to 40 micrograms/ml. The method is accurate (101.0 +/- 5.4%) and precise (maximum coefficient of variation of 8%). It provides a simple and time-saving alternative to existing methods and is particularly suitable for pharmacokinetic studies. PMID- 1517296 TI - Sensitive determination of josamycin and rokitamycin in plasma by high performance liquid chromatography with fluorescence detection. AB - Rokitamycin and josamycin were successfully derivatized with dansylhydrazine in 20 min at 60 degrees C. Rokitamycin and josamycin levels were determined in plasma after ion-pair extraction into hexane-isoamyl alcohol with lauryl sulphate and precolumn derivatization. Resolution was obtained by liquid chromatography with fluorescence detection (352/537 nm) in 12 min. The limit of detection was 20 ng/ml macrolide starting from 1 ml of plasma, and linearity was demonstrated between 50 and 400 ng/ml. Inter-run coefficients of variation were 10.2% at 100 ng/ml and 9.1% at 300 ng/ml. The system was reliably used for pharmacokinetic studies in plasma. PMID- 1517297 TI - Development and use of a stability-indicating high-performance liquid chromatographic assay for Meldrum's acid. AB - A high-performance liquid chromatographic method was developed that separates Meldrum's acid from its primary decomposition products, malonic acid and acetone. The method uses a reversed-phase column under isocratic conditions, with detection by ultraviolet absorption at 210 nm. Quantitation of the parent molecule and the acid decomposition product was possible over concentration ranges of 0.1-10.0 and 0.1-2.0 mg/ml, respectively. Acetone could be determined only at much higher concentrations. Using the malonic acid concentration as a measure of decomposition, this method was used to determine the hydrolytic stability of Meldrum's acid and its skin penetration properties. PMID- 1517298 TI - Rapid determination of creatine, phosphocreatine, purine bases and nucleotides (ATP, ADP, AMP, GTP, GDP) in heart biopsies by gradient ion-pair reversed-phase liquid chromatography. AB - A simple binary solvent method has been developed for the simultaneous determination of creatine (Cr), phosphocreatine (PCr), ATP, ADP, AMP, GTP, GDP, IMP, NAD, inosine, adenosine, hypoxanthine and xanthine. This allows separation of the most important nucleotides present in myocardial biopsies as, for example, in studies using 31P NMR spectroscopy. In NMR spectra ATP and PCr are the only visible high-energy phosphates, therefore the status of other nucleotides and bases cannot be determined. The nucleotides, AMP degradation products, PCr and Cr in pig and rat heart muscle were resolved with 35 mM K2HPO4, 6 mM tetrabutylammonium hydrogensulfate buffer, pH 6.0, and a binary acetonitrile gradient on medium-bore, 250 mm or 125 mm x 3.9-4.6 mm I.D. steel octadecyl bonded (C18) columns at a flow-rate of 1.5 or 1.0 ml/min. This method, optimized for use with older high-performance liquid chromatography pumps (100 microliters displacement heads), resolves the major porcine and rat myocardial nucleotides and degradation products within 22 min. The amounts found in normoxic porcine muscle are: Cr 9.21 +/- 0.75; hypoxanthine 1.40 +/- 0.14; PCr 7.20 +/- 1.2; IMP 1.34 +/- 0.13; beta NAD 1.82 +/- 0.23; AMP 0.10 +/- 0.04; GDP 0.05 +/- 0.02; ADP 1.23 +/- 0.09; GTP 0.19 +/- 0.01; ATP 4.45 +/- 0.32 mumol/g wet weight. The method, incorporating adenosine tetraphosphate as an internal standard, allows the documentation of changes in both the high-energy phosphates and their degradation products in a single analysis of myocardial samples as small as 200 micrograms (wet weight). PMID- 1517299 TI - Glassy carbon pre-column for direct determination of acetylcholine and choline in biological samples using liquid chromatography with electrochemical detection. AB - The determination of acetylcholine and choline has been quite successfully accomplished using liquid chromatography with electrochemical detection following the original reports of Potter et al. [J. Neurochem., 41 (1984) 188]. A post column reactor containing acetylcholinesterase and choline oxidase allows conversion of the desired species into hydrogen peroxide, an electrochemically active substance. However, the direct injection of tissue homogenates and other biological samples into such a system exhibits quite large solvent fronts and unidentified peaks. Using a pre-column packed with glassy carbon particles, we were able to dramatically decrease the size of the solvent front for such injections and tentatively identify the unknown peaks to be caused, at least in part, by common catecholamines. The glassy carbon pre-column, in addition to increasing the selectivity of the results, allowed the required chromatographic time per sample to be decreased from 20 to 10 min. PMID- 1517300 TI - Determination of platelet monoamine oxidase activity by high-performance liquid chromatography with electrochemical detection. AB - A procedure for determining human platelet monoamine oxidase (MAO) with dopamine (DA) as substrate is described. High-performance liquid chromatography (HPLC) with electrochemical detection (ED) was used to separate and detect components of the reaction mixture. The method for platelet preparation was also improved and only 2 ml of blood were required. Following a 10-min incubation of the platelet preparation with DA in 0.1 M Tris buffer (pH 9.0), excess DA substrate was removed by adsorption on a cation-exchange resin. The reaction product, 3,4 dihydroxyphenylacetaldehyde, was adsorbed on acid-washed alumina, eluted with 0.1 M perchloric acid and analyzed by HPLC. Simple, clean chromatograms were obtained with good reproducibility using 3,4-dihydroxybenzylamine as an internal standard. The within-sample, between-samples and between-day relative standard deviations were 0.9, 3.7 and 6.1%, respectively. The apparent Michaelis constant and maximum velocity were 0.10 mM and 0.37 nmol/min.mg protein, respectively. This HPLC-ED method offers a good alternative to methods using radioactivity. PMID- 1517301 TI - Lipophilicity determination of some monoamine oxidase inhibitors: the effect of methanol and ammonium chloride. AB - The lipophilicity (RM value) of seventeen monoamine oxidase inhibitory drugs was determined by reversed-phase thin-layer chromatography, and the effect of salt concentration on the reversed-phase retention was studied by adding ammonium chloride to the eluent. Each drug exhibited regular retention behaviour, its RM value linearly decreasing with increasing concentration of methanol in the eluent. Ammonium chloride decreased the retention: the effect was higher at lower salt concentrations, which indicates that the phenomenon is of saturation character. The influence of ammonium chloride depended on the concentration of methanol (on the dielectric constant of the eluent) suggesting that methanol suppresses the dissociation of ammonium chloride resulting in a modified salting in effect. PMID- 1517302 TI - Analysis of 3,5,6-trichloropyridinol in human urine using negative-ion chemical ionization gas chromatography-mass spectrometry. AB - A sensitive gas chromatographic-negative-ion chemical ionization mass spectrometric (GC-NCI-MS) method was developed to measure levels of the chlorpyrifos metabolite 3,5,6-trichloropyridinol (3,5,6-TCP) in human urine. The metabolic 3,5,6-TCP was isolated from urine by acid hydrolysis of urine aliquots, followed by diethyl ether extraction. The residues of ether extraction were taken up in o-xylene and derivatized with N-(tert.-butyldimethylsilyl)-N methyltrifluoroacetamide (overall five-fold concentration). The structural isomer 3,4,5-trichloropyridinol was used as an internal standard in this analysis. This method was found to be linear for the determination of 3,5,6-TCP over the range 0.8-792 ng/ml. The limit of detection for 3,5,6-TCP in human urine was estimated to be 0.5 ng/ml. Low levels of 3,5,6-TCP (1-18 ng/ml of urine) were identified in control human urine samples. Structural confirmation of the background 3,5,6-TCP was obtained via GC-NCIMS-MS analysis. PMID- 1517303 TI - High-performance liquid chromatography-thermospray mass spectrometry of hydroxy polyunsaturated fatty acid acetyl derivatives. AB - A method for the determination of hydroxy-polyenoic acids has been developed. Hydroxy groups of hydroxy-polyunsaturated fatty acid were acetylated by acetic anhydride, and the mixture was partially purified on a Sep-Pak C18 cartridge and analysed by high-performance liquid chromatography combined with thermospray mass spectrometry. Using this method, fifteen kinds of hydroxy-polyunsaturated fatty acid derivative could be detected simultaneously within 30 min on a selected-ion monitoring detection chromatograph without a gradient system. Generally, the base ion, [M + H - n(60)]+, is produced through elimination of acetic acid (n = number of the hydroxy group of hydroxy-polyunsaturated fatty acid). The detection limit for these derivatives was ca. 0.2 pmol at the levels of hydroxy-polyenoic acids prior to derivatization. They could be analysed in the range 0.5-25 pmol. The assay was successfully applied to hydroxy-polyunsaturated fatty acids from an incubation mixture of rat brain homogenate to which polyunsaturated fatty acid was added. PMID- 1517304 TI - Rapid and efficient purification of cimetropium bromide and mifentidine drug metabolite mixtures derived from microsomal incubates for analysis by mass spectrometry. AB - A comparative study of the use of organic solvent extraction versus Sep-Pak C18 cartridges in the recovery and analysis of phase I (unconjugated) drug metabolites using mass spectrometry is presented. Standard mixtures of putative metabolites of the anticholinergic drug cimetropium bromide and the H2-antagonist mifentidine were purified from inactivated liver microsomal preparations using both methods, and subsequently the recovery of each compound was quantitated. In general, the percentage recovery and degree of purification were greater when using Sep-Pak C18 cartridges compared with organic solvent extraction. Even more efficient recovery was achieved when zinc sulphate precipitation of proteins in the liver microsomal mixtures was carried out prior to analysis. Also, the HPLC grade solvents used in this study contained a variety of ultraviolet-inactive, hydrophobic components. This leads to problems of suppression in fast atom bombardment mass spectrometric analysis. Using Sep-Pak C18 cartridges directly prior to analysis by fast atom bombardment with single or tandem mass spectrometry leads to far superior mass spectral results compared with organic solvent extraction. PMID- 1517305 TI - Monitoring of ajmaline in plasma with high-performance liquid chromatography. AB - A rapid, reliable and sensitive assay for routine determination of ajmaline in plasma by high-performance liquid chromatography with fluorimetric detection is presented. A low limit of detection in plasma (less than 1 ng/ml ajmaline) could be achieved by the extraction of plasma samples and the use of fluorimetric detection. Deproteinization of the plasma sample instead of extraction, or the use of an ultraviolet detector, yielded a higher limit of detection (less than 50 ng/ml). Two different eluents were studied. Eluent 1 allowed clear separation of ajmaline from isoajmaline and sandwicine, but did not separate isoajamaline from sandwicine. With eluent 2, separation of isoajmaline and sandwicine was achieved, but separation of ajmaline from sandwicine was less optimal than with eluent 1. Therefore, eluent 1 was used for further clinical studies. No interference was observed from therapeutic doses of other commonly co-administered drugs, such as acetylsalicylic acid, digoxin, digitoxin, ranitidine, dopamine, dobutamine, furosemide, captopril or glycerol trinitrate. In addition, the chemical stability of ajmaline and a possible rearrangement of ajmaline to its stereoisomers isoajmaline and sandwicine was studied in vivo and in vitro. Ajmaline proved to be unusually stable under both in vivo and in vitro conditions. PMID- 1517306 TI - Automated high-performance liquid chromatography of iopentol in human plasma and whole blood using on-line dialysis as sample preparation. AB - A fully automated high-performance liquid chromatographic method has been developed for the analysis of the radiographic contrast agent iopentol in human plasma and whole blood. This method is based on on-line sample preparation with dialysis followed by pre-column enrichment of the dialysate. The method was compared with a manual sample preparation method based on protein precipitation with tetrahydrofuran. The inter-assay and intra-assay variations and the limits of quantitation were the same for both methods. The on-line combination of dialysis and column-switching high-performance liquid chromatography was shown to be a reliable and time-saving technique for monitoring iopentol in human whole blood and plasma. PMID- 1517307 TI - Avid AL, a synthetic ligand affinity gel mimicking immobilized bacterial antibody receptor for purification of immunoglobulin G. AB - Avid AL is an affinity gel designed for the purification of immunoglobulin G (IgG). The gel was prepared by first reacting Sepharose with 3,5-dichloro-2,4,6 trifluoropyridine and 4-dimethylaminopyridine and then with 2-mercaptoethanol. The IgG purified by Avid AL is about 95% pure. The binding parameters of Avid AL for the whole IgG, Fab and Fc fragment and the stability of gel were investigated. The IgG bound to Avid AL can be eluted with an acidic buffer or with a novel neutral buffer containing electron donors. The development of such a mild neutral elution buffer is described. Application of Avid AL in a rapid gram scale IgG purification was demonstrated. The possible mechanism of IgG binding is discussed. PMID- 1517308 TI - Immobilized lectin columns: useful tools for the fractionation and structural analysis of oligosaccharides. AB - Elucidation of the binding specificity of a concanavalin A-Sepharose column led to the possibility of the affinity chromatography of oligosaccharides and glycopeptides with the use of immobilized lectin columns. Subsequent addition of immobilized erythroagglutinating phytohaemagglutinin, Aleuria aurantia lectin, Datura stramonium agglutinin, Ricinus communis agglutinin and Allomyrina dichotoma agglutinin to the range of well characterized lectin columns has afforded a way to fractionate a mixture of N-linked oligosaccharides even to a single component. PMID- 1517309 TI - Immobilization of protein ligands with methyl vinyl ether-maleic anhydride copolymer. AB - Methyl vinyl ether-maleic anhydride copolymer (MMAC) is a water-insoluble polymer with an acid anhydride group which reacts with amino groups of ligands to form stable amide bonds. MMAC was used to immobilize protein ligands on two kinds of supports, the wells of plastic microtitre plates for enzyme-linked immunosorbent assay and related methods, and gels for affinity adsorbents. The wells were first coated with MMAC and then allowed to react with proteins. The immobilization of proteins by this method was efficient and occurred in a dose-dependent manner. Shodex Et123, a gel having amino groups, was incubated with MMAC, and then the activated Shodex was used to immobilize high concentrations of proteins. Concanavalin A-Shodex thus obtained had high affinities and was successfully used for the high-performance liquid affinity chromatography of sugar derivatives on a short column. PMID- 1517310 TI - Immobilized ferredoxins for affinity chromatography of ferredoxin-dependent enzymes. AB - An immobilized ferredoxin more stable than the conventional immobilized spinach ferrodoxin was prepared by reacting CNBr-Sepharose with ferredoxins isolated from barley and Synechococcus vulcanus, a thermophilic blue-green alga. The dissociation constants of immobilized ferredoxin from spinach, barley and S. vulcanus for spinach ferredoxin-NADP reductase were 0.922, 2.505 and 5.209 microM, respectively, whereas those for barley ferredoxin-NADP reductase were 1.159, 0.579 and 2.851 microM, respectively. The order of stability was S. vulcanus greater than barley greater than spinach. The immobilized ferredoxin was applied to the simultaneous detection of ferredoxin-dependent enzymes in spinach chloroplasts. Over 20 polypeptides were detected. Synechococcus ferredoxin could also be immobilized on a Toyopearl gel and repeatedly used in an automated high performance liquid chromatographic system. PMID- 1517311 TI - Membrane-based receptor affinity chromatography. AB - Membrane-based receptor affinity chromatography (MRAC), which utilizes the molecular recognition between an immobilized receptor and its soluble protein ligand, has been developed for the purification of human interleukin-2 and related biomolecules. The multi-purpose affinity membrane used in this study consisted of a soluble form of interleukin-2 receptor (IL-2R) chemically bonded to hollow-fiber membranes in an oriented fashion. A model system involving anti Tac-H (a humanized monoclonal antibody to IL-2R) was used to study the important factors influencing the performance of MRAC, including support morphology, mass transfer rate and adsorption kinetics. All three are shown to be highly efficient. MRAC has been successfully applied to the purification of anti-Tac-H, recombinant human interleukin-2 (rIL-2) and interleukin 2-Pseudomonas exotoxin fusion protein (IL2-PE40). Overall, MRAC was found to be a viable, scalable and extremely productive affinity purification method. PMID- 1517312 TI - Kinetic aspects of membrane-based immunoaffinity chromatography. AB - With a view towards the efficient large-scale purification of recombinant proteins, factors influencing antigen-antibody adsorption kinetics were studied in a model hollow-fiber membrane-based immunosorbent. Non-diffusion-controlled, homogeneous adsorption kinetics are approached in membranes. It is shown that adsorption kinetics, rather than mass transfer, first becomes limiting in membrane-based immunoaffinity chromatography (MIC). Antigen adsorption is not kinetically limited, even at low feed-stream antigen concentrations. Binding efficients approach theoretical values when antibody coupling densities are decreased sufficiently. Antigen breakthrough during adsorption occurs near the membrane's observed binding capacity. The results of these kinetic studies were essential in the development of highly efficient and productive MIC systems for the purification of three recombinantly produced biotherapeutics, interferon alpha 2a, interleukin-2 and interleukin-2 receptor. PMID- 1517313 TI - Short-cut method for predicting the productivity of affinity chromatography. AB - A method was developed for predicting the productivity P (amount of the target protein recovered per unit volume per unit time) of affinity chromatography (AFC) and similar chromatographic operations. The constant-pattern approach was employed for describing the breakthrough curve. It was found that P increases with increasing u at low u regions and there is a maximum in the P-u curve. The u value that gives the maximum P (uM) was derived as a function of the number of transfer units, n. The experimental breakthrough curves for several different packing media systems such as 40- and 10-microns porous particles, 2.5-microns non-porous particles and surface-derivatized membrane media were measured, from which the n values were determined. The uM values were then calculated using the n values. It is suggested that the present method is useful for the rapid survey of the operating conditions in scaling-up AFC and similar chromatographic operations. PMID- 1517314 TI - Arginine-tail method, an affinity tag procedure utilizing anhydrotrypsin agarose. AB - The arginine-tail method is a recently developed affinity tag procedure utilizing immobilized anhydrotrypsin for specific enrichment of a recombinant protein. Three model proteins (originally human beta-galactoside-binding lectin with a relative sub-unit molecular mass of 14,000) were prepared by mutagenesis, each of which has a tail of either Arg, Gly-Arg, or Gly-Gly-Arg at the C-terminus. All of them retained their original sugar-binding activity and antigenicity, and became recognizable by anhydrotrypsin. They were adsorbed on an anhydrotrypsin-agarose column at pH 5 after treatment with 4 M urea or 10 mM HCl to expose the C terminal tails. The adsorbed arginine-tailed lectins were eluted either specifically with benzoylglycylarginine (Bz-Gly-Arg) or with 5 mM HCl. Added arginine was removed by carboxypeptidase B, but very slowly. When urea-denatured Escherichia coli lysate containing one of the arginine-tailed lectins was applied to the column, the lectin was adsorbed together with some host proteins, which are expected to have arginine or lysine at their C-termini. However, more than a ten-fold enrichment was attained by this procedure. The described method would be useful for purifying various recombinant proteins, even those which are inactive as a result of mutagenesis. The smallest tag arginine at the C-terminus should have a minimum effect on both the structure and function of a target protein. PMID- 1517315 TI - Novel affinity separations based on perfluorocarbon emulsions. Use of a perfluorocarbon affinity emulsion for the purification of human serum albumin from blood plasma in a fluidised bed. AB - A perfluorocarbon affinity emulsion has been generated by homogenisation of a saturated perfluorocarbon oil with a polymeric fluorosurfactant based on poly(vinyl alcohol) (relative molecular mass 9000-10,000) previously derivatised with the triazine dye CI Reactive Blue 4. This affinity emulsion has subsequently been cross-linked in situ and used in a fluidised bed for the purification of human serum albumin (HSA) from blood plasma. HSA was quantitatively recovered in a semi-continuous fashion from plasma at an average purity of 90 +/- 3.3%. The albumin binding capacity of the emulsion has been shown to be 0.59 mg/ml by frontal analysis corresponding to a mol/mol ligand usage of 13.5%. In all regards, when used in a fluidised bed, the emulsions have been shown to behave as a normal chromatographic material. They are stable under operational conditions with no coalescence being observed for periods greater than 1 year. These novel liquid affinity supports present an exciting opportunity to develop a range of unit operations for the continuous purification of proteins. PMID- 1517316 TI - Galactosylation as a tool for the stabilization and immobilization of proteins. AB - This paper presents a brief overview of the role that the carbohydrate moieties of biologically active glycoproteins play in the stabilization and oriented immobilization of these proteins on solid supports. The synthetic galactosylation of hydrophobic areas or their surroundings on the protein surface improves the structural stability of native proteins against inactivation by the interaction of water with hydrophobic clusters. The lowering of the degree solvation of tyrosine residues in galactosylated trypsin and the model substance N carbobenzoxy-L-glutamyl-L-tyrosine was proved by Raman spectroscopy. D-Galactose residues can be selectively oxidized, either with periodate or enzymatically, and the aldehyde groups thus formed are used for the immobilization of glycoproteins on solid supports with hydrazide groups under mild conditions. PMID- 1517317 TI - Improved affinity chromatographic purification of D-mannose-N-acetyl-D glucosamine-specific lectin from the bark of Sophora japonica eliminating the loss by sugar specific self-aggregation. AB - A novel D-mannose-N-acetyl-D-glucosamine-specific lectin of Sophora japonica bark, B-SJA-II, which showed self-aggregation based on sugar specificity, was purified by affinity chromatography on maltamyl-Sepharose subsequent to chromatographic separation on lactamyl-Sepharose to remove a major D-galactose-N acetyl-D-galactosamine specific lectin, B-SJA-I. However, the yield of this method was low as a result of the sugar-specific precipitation and binding to other glycoproteins. A modified method was developed to circumvent this problem. All the purification procedures, except for the final chromatographic separation, were carried out in the presence of the haptenic sugar and the sugar-specific adsorption of B-SJA-II onto the adsorbent was carried out in a dialysis bag by gradually removing the sugar. This method gave a yield eight times higher than the original method. PMID- 1517318 TI - Selective clean-up method using an immunoaffinity column following radioimmunoassay of prostaglandin F2 alpha in biological fluids. AB - A selective clean-up method using an immunoaffinity column followed by radioimmunoassay (RIA) was developed for determining prostaglandin F2 alpha (PGF2 alpha) in human urine and plasma. Polyclonal antibody raised against PGF2 alpha, obtained from rabbits, was coupled to a tresyl-activated support based on a synthetic hydrophilic resin, TSKgel Tresyl-Toyopearl 650M, and used as the stationary phase for the immunoaffinity column. A human urine or plasma sample was introduced to this column, and PGF2 alpha was eluted with methanol-water (50:50, v/v) after the column had been washed. The eluate was subjected to competitive RIA for PGF2 alpha. The cross-reactivities of the RIA to a number of endogenous prostanoids, except PGD2, were negligible and the sensitivity was 4 pg/tube (p less than 0.05), giving a detection limit of 40 pg/ml when 1 ml of plasma or urine was available. The recoveries of plasma and urine samples were 98 108% and 96-106%, respectively, and their assay variances were 7-23%. The concentrations of endogenous PGF2 alpha in plasma and urine used here were estimated to be 72 and 98 pg/ml, respectively. This method should be very useful for various biological samples because of its good specificity, sensitivity, reliability and reproducibility. PMID- 1517319 TI - Isolation and characterization of isolectins from Erythrina variegata seeds. AB - Three isolectins were isolated from seeds of Erythrina variegata (Linn.) var. Orientalis by ion-exchange chromatography, followed by affinity chromatography on lactose-Sepharose 4B and acid-treated Sepharose 4B columns. The purified isolectins (EVLI, EVLII and EVLIII) are all specific for galactopyranosides and N acetylgalactosamine, and their affinities for simple sugars are EVLIII greater than EVLII greater than EVLI. EVLI and EVLIII are homodimers made up of an A subunit of molecular mass 36,000 and a B-subunit of molecular mass 33,000, whereas EVLII is a heterodimer composed of the A- and B-subunits. Upon treatment with trifluoromethansulphonic acid, the molecular masses of both subunits decreased to 31,000. Rechromatography of EVLII on the acid-treated Sepharose 4B column again produced the homodimeric lectins (EVLI and EVLIII). It is suggested that the constituent subunits of Erythrina variegata isolectins are eschangeable with each other in vitro. PMID- 1517320 TI - Purification and characterization of carbohydrate-binding peptides from Lotus tetragonolobus and Ulex europeus seed lectins using affinity chromatography. AB - Carbohydrate-binding peptides of several anti-H(O) leguminous lectins were obtained from endoproteinase Asp-N or Lys-C digests of L-fucose-binding Lotus tetragonolobus lectin (LTA) and Ulex europeus lectin I (UEA-I) and from that of a di-N-acetylchitobiose-binding Ulex europeus lectin II (UEA-II) by affinity chromatography on columns of Fuc-Gel (for LTA and UEA-I) and on a column of a mixture of several oligomers of N-acetyl-D-glucosamine (GlcNAc) coupled to Sepharose 4B (GlcNAc oligomer-Sepharose 4B) (for UEA-II). These peptides were retained on the Fuc-Gel or GlcNAc oligomer-Sepharose 4B column and were presumed to have an affinity for the columns. The amino acid sequences of the retarded peptides were determined using a protein sequencer. PMID- 1517321 TI - Determination of the carbohydrate-binding site of Bauhinia purpurea lectin by affinity chromatography. AB - To determine the carbohydrate-binding site of Bauhinia purpurea lectin (BPA), a D galactose- and lactose-binding lectin, a peptide which interacts with lactose was purified from endoproteinase Asp-N digests of BPA by chromatography on a lactose Sepharose column. It consists of nine amino acids and its amino acid sequence is Asp-Thr-Trp-Pro-Asn-Thr-Glu-Trp-Ser. A tryptic fragment with the ability to interact with lactose was also purified and found to contain this sequence, consisting of nine amino acids. This nonapeptide was aligned in a part of the metal-binding region conserved in all legume lectins. The chemical synthesis of the nonapeptide was carried out by a solid-phase method and the synthetic peptide showed a lactose-specific binding activity in the presence of calcium. A chimeric lectin gene was constructed using a cDNA coding BPA in which the nonapeptide sequence was replaced by the corresponding region of the alpha-D-mannose binding Lens culinaris lectins. Although BPA is specific for beta-D-galactose, the chimeric lectin expressed in Escherichia coli was found to bind alpha-D-mannosyl bovine serum albumin and this binding was inhibited by D-mannose. PMID- 1517322 TI - Evaluation of the mode of binding of immunoglobulin to activated agarose. AB - Determining the orientation of the immobilization of proteins to solid-phase matrices is of critical importance in the development of systems that employ immobilized proteins. Among these are enzyme-linked immunoassays, immobilized enzymes and affinity chromatography matrices. To determine the orientation of immunoglobulin G (IgG) on activated agaroses, we coupled the immunoglobulin covalently to various activated matrices. The IgG was then cleaved with papain and the liberated fragments collected and analyzed using high-performance liquid chromatography. Only Fab fragments could be detected regardless of the activation method used. This implies that IgG binds to these matrices predominantly via the Fc domain. In order to develop a quantitative method of measuring the Fab and Fc fragments, we compared the binding of IgG and its papain cleavage fragments to S Zephyr columns and Mono-S columns. Comparison between these columns showed that IgG is bound more tightly to the S-Zephyr column and, in contrast, its retention on Q-Zephyr is less than on a comparable Mono-Q column. The resolution of IgG and its fragments was better in all cases on S-Zephyr than on Mono-S under the conditions employed. PMID- 1517323 TI - Use of antibody fragments in immunoaffinity chromatography. Comparison of FV fragments, VH fragments and paralog peptides. AB - Some new antibody fragments have recently been described: FV fragments (Mr 25,000), VH fragments or "dAbs" (12,500) and paralog peptides (1000-2000). FV fragments, VH fragments and a paralog peptide that had been derived from a parent antibody with a specificity for hen lysozyme were produced. All three reagents were immobilized on Sepharose and evaluated for their ability to recover hen lysozyme from "spiked" serum and to separate hen lysozyme from turkey lysozyme. The FV column had excellent specificity for hen lysozyme, the VH column had significantly reduced specificity and the paralog peptide column did not bind lysozyme at all. PMID- 1517324 TI - Affinity chromatographic purification of immunoglobulin M antibodies utilizing immobilized mannan binding protein. AB - A method is described for the rapid and efficient affinity chromatographic purification of murine monoclonal immunoglobulin M (IgM) which utilizes immobilized rabbit mannan binding protein (MBP). This solid-phase matrix is shown to bind IgM-class antibodies from a variety of species. Conditions reported show a binding capacity of IgM from murine ascites of nearly 1 mg/ml of immobilized MBP support. The prepared gel is shown to possess an ability to bind not only mouse IgM, but also human and bovine IgM, although with a lesser affinity. The matrix can be regenerated and reused at least ten times without any apparent loss of binding capacity or specificity. Mouse monoclonal IgM purified from ascites fluid using this method is greater than 95% pure as shown by high-performance liquid chromatography analysis. PMID- 1517325 TI - Affinity purification of antibodies using immobilized FB domain of protein A. AB - A continuous method for the efficient digestion of protein A into active fragments (FB, Mr = 7000) using immobilized trypsin was developed. These fragments originate from almost identical five-repeated monovalent Fc-binding units of 58 residues each. The fragments obtained were found to be similar to the recently described genetically engineered fragment B. Antibody-binding characteristics of the FB domain and also of intact protein A, immobilized on to adipic dihydrazide-modified Eupergit CB6200 beads, were investigated. Based on the experimental data obtained, a high-performance liquid chromatographic column containing C30N Eupergit C-immobilized FB domain was prepared and its performance in antibody purification was compared with that of Eupergit C-immobilized intact protein A. PMID- 1517326 TI - Calcium-modulated conformational affinity chromatography. Application to the purification of calmodulin and S100 proteins. AB - The purification of proteins by affinity chromatography is based on their highly specific interaction with an immobilized ligand followed by elution under conditions where their affinity towards the ligand is markedly reduced. Thus, a high-degree purification by a single chromatographic step is achieved. However, when several proteins in the crude mixture share affinity to a common immobilized ligand, they may not be resolved by affinity chromatography and subsequent "real" chromatographic purification steps may be required. It is shown that by using properly selected gradient elution conditions, the affinities of the various proteins towards the immobilized ligand may be gradually modulated and their separation may be achieved. This is exemplified by the isolation and separation of a group of Ca(2+)-activated proteins, Calmodulin, S100a and S100b, from bovine brain extract, using a melittin-Eupergit C affinity column which is developed with Ca(2+)-chelator gradients. As expected, separation of the three proteins into individual peaks, eluted in order of increasing affinity to the matrix, was obtained. Sigmoid selectivity curves calculated from the elution volumes under different elution conditions for each of the proteins were obtained, illustrating the chromatographic behaviour of the gradient affinity separation system. PMID- 1517327 TI - High-performance affinity chromatography system for the rapid, efficient assay of glycated albumin. AB - A high-performance affinity chromatographic system was constructed and shown to permit highly reproducible, rapid, automatic assays of serum glycated albumin (GA) by separation of albumin (Alb) on an anion-exchange column (Asahipak ES 502N) packed with a vinyl alcohol copolymer bearing diethylamino groups and consecutive separation of GA on a column packed with a vinyl alcohol copolymer bearing boronate groups. The first column selectively retained Alb free of other serum proteins and permitted at least a 95% recovery of sample Alb. The purity of the Alb peak was confirmed by two-dimensional electrophoresis. Chromatographic analyses of human serum Alb incubated with glucose on the second column showed that the peak area for GA increased in accordance with the incubation time and suggested selective adsorption of GA on the second column. Optimization of the conditions for the two-column system reduced the analysis time to 10 min. Analyses of human sera with the present system showed GA to be 16.1 +/- 1.1% (mean +/- S.D.) of total Alb in non-diabetic children and 39.9 +/- 9.1% (mean +/- S.D.) in diabetic children (0-17 years old). PMID- 1517328 TI - Artificial immunoglobulin G-binding protein mimetic to staphylococcal protein A. Its production and application to affinity purification of immunoglobulin G. AB - Staphylococcal protein A consists of a single polypeptide with five immunoglobulin G (IgG)-binding domains, which are linked as E-D-A-B-C in this order from the amino terminal. The DNA coding domains A-B were polymerized one to six times linearly, taking advantage of the non-palindromic nucleotide sequence of the AccI recognition site and the resultant DNAs were inserted in pTRP vector carrying trp promoter. The artificial IgG-binding proteins [pA(AB)1-6], which had been expressed in Escherichia coli JM109, were purified by methods involving IgG Sepharose affinity chromatography. Among pA(AB)1-6 immobilized on cyanogen bromide-Sepharose, pA(AB)4-Sepharose was the highest in IgG-binding capacity at the same level of mg protein per ml gel, about 30% higher than protein A Sepharose. At 8 mg protein per ml gel, it bound and eluted about 24 mg of IgG from rabbit serum. Its IgG-binding capacities were the highest with porcine, rabbit, human and guinea pig sera, intermediate with bovine, horse and sheep sera and the lowest with mouse, goat, rat and chicken sera. PMID- 1517329 TI - Purification of sufficiently gamma-carboxylated recombinant protein C and its derivatives. Calcium-dependent affinity shift in immunoaffinity and ion-exchange chromatography. AB - Protein C, which is an important anti-thrombotic factor in the blood coagulation cascade, undergoes several post-translational modifications. gamma-Carboxylation on nine glutamic acid residues at the N-terminal region of the light chain [gamma carboxylated glutamic acid (Gla) domain] is considered to be critical for full anti-clotting activity. It is also known that when recombinant protein C is expressed in animal cells this particular modification is often lost. We were successful in preparing a monoclonal antibody (PC01) which distinguishes the sufficiently gamma-carboxylated protein from the rest by its specific affinity for the Ca(2+)-induced conformational change of the former, and thereby developed a simple process of purifying sufficiently gamma-carboxylated protein C. Culture supernatant of Chinese hamster ovary cell transformants was first applied to Q Sepharose and recombinant protein C was partially purified. It was then loaded onto a PC01 affinity column in the presence of 5 mM calcium chloride. Sufficiently gamma-carboxylated protein C was retained while insufficient carboxylated protein C quickly passed through. The former was eluted with 5 mM EDTA efficiently and with high purity, contained eight Gla units per molecule, and had similar anti-clotting activity. The flow-through was relatively impure protein C which contained five Gla units per molecule and showed limited anti clotting activity. We extended the application of the Ca(2+)-induced conformational change to conventional ion-exchange chromatography. The sufficiently gamma-carboxylated protein C was found to elute earlier in the salt gradient from an anion-exchange column in the presence of 5 mM calcium chloride being fully separated from the insufficiently carboxylated protein C.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1517330 TI - Interactions and uses of antisense peptides in affinity technology. AB - Antisense peptides, amino acid sequences encoded in the antisense strand of DNA, can interact with significant affinity and selectivity with their corresponding sensepeptides. Experimentally, sense-antisense peptide recognition has been observed repeatedly. However, skepticism about the biological relevance of this phenomenon has persisted. This is due in part to the unexpected and somewhat couterintutive nature of the interaction as well as to its non-universality as an empirical observation. Nonetheless, antisense peptides in several cases investigated so far have been used as immobilized ligands for the successful affinity chromatographic separation of native (sense) peptides and proteins. For example, immobilized antisense peptides corresponding to Arg8-vasopressin (AVP) have been used to separate vasopressin from oxytocin chromatographically as well as to affinity capture AVP-receptor complex. These results, together with improved understanding of the general features of amino acid sequence which drive antisense-sense peptide interactions as well as new ideas for making antisense peptides chimeras, are beginning to suggest improved ways to make antisense related peptides as affinity agents for separation as well as for other biotechnology applications. PMID- 1517331 TI - Interaction of amphipathic model lipopeptides with phospholipid bilayers. AB - In order to investigate the conformation and localization of lipopeptides in lipid bilayers, a basic model peptide with a long alkyl chain, Ac-Ser-Val-Lys-Amy Ser-Trp-Lys-Val-NHCH3 Amy-1; Amy = alpha-aminomyristic acid) was synthesized. Its interaction with neutral and acidic phospholipid bilayers was studied by circular dichroism (CD) spectroscopy, dye leakage and fluorescence measurements. Another peptide, Ac-Leu-Ala-Arg-Leu-Trp-Amy-Arg-Leu-Leu-Ala-Arg-Leu-NHCH3 (Amy-2), which was prepared previously, was used for comparison. The CD data indicated that Amy 1 took a beta-turn and/or a beta-structure in the absence and presence of liposomes. Amy-2 formed a beta-structure in aqueous solution and an alpha-helical structure in liposomes. The dye leakage ability of Amy-1 was much weaker than that of Amy-2. Fluorescence spectroscopic data suggest that the peptides are immersed in lipid bilayers. Based on these results, discussion is made in terms of localization of the peptides in lipid bilayers. PMID- 1517332 TI - Purification and partial characterization of phospholipase A2 isoforms from human placenta. AB - Five isoforms of the human placental phospholipase A2 were identified and purified to near homogeneity. The purification of these enzymes involved gel permeation, ion-exchange and affinity chromatography. The apparent relative molecular mass of these proteins is 70,000 as determined by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. These enzymes have pH optima of 7 and 8. Two-dimensional gel electrophoresis of these enzymes revealed distinct pH optima for each of the isoforms with values ranging from 4.0 to 6.5. Three of the isoforms require calcium for activity whereas the other two forms exhibit 50% of their maximum activity without the presence of calcium. PMID- 1517333 TI - Trypsin and affinity chromatography. AB - Affinity adsorbents for trypsin which were prepared by immobilizing product-type ligands, that is, peptides having C-terminal arginine, proved to be effective not only for preparative purposes but also for basic research on molecular recognition. The properties of the binding site of trypsin were revealed by chromatographic experiments. Quantitative analysis based on the theory of frontal affinity chromatography proved to be extremely effective. As an extension of the product-type ligands, peptide argininals were also used and information on the mechanism of action of these inhibitors was obtained. Anhydrotrypsin, which lost the hydroxyl group of Ser183, was found to gain increased binding ability for product-type compounds. This inactivated enzyme was also used as an immobilized ligand and the unique affinity adsorbent thus prepared proved to be extremely effective for the separation of peptides and recombinant proteins based on their C-terminal structures. High-performance affinity chromatography of trypsin and related enzymes using a polymer-based support was also developed. PMID- 1517334 TI - Preparation of immunoaffinity mini-columns for the analysis of platelet activating factor (PAF) in biological samples. AB - Using an antibody to BN 52719, an analogue of platelet activating factor (PAF), immunoaffinity mini-columns for the separation of PAF from biological samples were prepared. Rabbits were immunized with BN 52719 and immunoglobulin G (IgG) from the antiserum was coupled with Sepharose 4B. The resulting suspension of the IgG-coated Sepharose 4B in 25 mM phosphate buffer (pH 6.9) was poured into a plastic mini-column (bed volume 2.0 x 0.8 cm). Stepwise elution of the column with methanol revealed that lyso-PAF is eluted with 20-30% methanol in water whereas PAF is eluted with 50-80% methanol. For the determination of PAF in biological samples, it is recommended that lipids are extracted from the samples and the extract, reconstituted in 20% methanol, is loaded on the column. The column is then washed with 50% methanol followed by elution of PAF with 80% methanol. A small amount of [3H]PAF is added to the samples for measurement of the recoveries of PAF during the procedures of extraction and elution. The PAF is then quantified by radioimmunoassay or bioassay. Employing the immunoaffinity mini-column and radioimmunoassay, the contents of PAF in macrophages and conditioned medium after stimulation with calcium ionophore A23187, or tumor promoters such as TPA and thapsigargin, were measured. PMID- 1517335 TI - Immunoenzymatic assay of dyes currently used in affinity chromatography for protein purification. AB - Cibacron Blue F3-GA, Basilen Blue E3-G and Procion Red HE-3B are dyes currently used in affinity purification, and are commonly determined by spectrophotometry with limited sensitivity. An assay method is described based on a specific immunochemical recognition of the dyes amplified by a final enzymatic reaction. The sensitivity is close to 1 ng/ml of dye and the method is applicable any time that sensitive and accurate results are necessary. This method has actually been applied with success to the determination of trace amounts of dyes in the presence of affinant protein. The method was also applied to the demonstration of dye leaching from affinity sorbents when treated under acidic and/or alkaline conditions. PMID- 1517336 TI - Affinity purification and affinity characterization of carbohydrate-binding proteins in bovine kidney. AB - Ca(2+)-dependent carbohydrate-binding proteins were purified from bovine kidney by two-step affinity chromatography on fetuin and heparin columns and subsequent anion-exchange high-performance liquid chromatography. On sodium dodecyl sulphate polyacrylamide gel electrophoresis, the purified fraction gave two protein bands corresponding to proteins of relative molecular mass 33,000 (p33) and 41,000 (p41), respectively. Although the proteins had no haemogglutinating activities towards human and rabbit erythrocytes, their carbohydrate-binding activity was examined by a newly developed method using horseradish peroxidase (HRP) and/or biotin-labelled glycoconjugates as affinity probes. They could bind in a Ca(2+) dependent manner to labelled fetuin and heparin in a specific and dose-dependent manner by solid-phase assay after immobilization on plastic plate surface. Inhibition assay of the binding revealed that N-acetylneuraminic acid is the most potent inhibitor of the proteins among the monosaccharides tested. Fucoidin and heparan sulphate most strongly inhibited the binding of the proteins to labelled heparin. Direct binding assay to acidic glycolipids prepared from bovine kidney showed that the proteins react with the ganglioside fraction but not with sulphatide [Gal(3-SO4) beta 1-1Cer]. These results indicated that the purified proteins have a significant affinity to charged oligosaccharides linking to glycoproteins, glycolipids and charged polysaccharides in a Ca(2+)-dependent manner. PMID- 1517337 TI - Affinity chromatography in purification of A1 adenosine receptors. AB - Purification of A1 adenosine receptor of rat brain membranes was performed using a newly developed affinity gel employing xanthine amine congener (XAC) as an immobilized ligand. The A1 adenosine receptor was solubilized with digitonin cholate from brain membranes and then purified by a sequential use of affinity chromatography on XAC-agarose, hydroxyapatite chromatography and reaffinity chromatography on XAC-agarose. The A1 adenosine receptor was purified ca. 45,000 fold with a yield of 5%. The final receptor preparation gave a single broad band on sodium dodecyl sulfate-polyacrylamide gel electrophoresis with a Mr approximately 34,000. This band was also shown to be specifically labelled with an affinity labelling reagent for A1 adenosine receptors. This purification method was also applicable for the complete purification of A1 adenosine receptors from rat testis and human brain membranes. PMID- 1517338 TI - Characterization of the interaction between human plasma fibronectin and collagen by means of affinity electrophoresis. AB - The interaction between human plasma fibronectin and different types and forms of collagen were analysed by affinity electrophoresis at different pH values. The fibronectin bound tightly to collagen type I, III and IV, but not to type V. The fibronectin interacted better with the denatured form of collagen type I (gelatin) than with the native form. At pH less than 5.5 the fibronectin exhibited much lower affinity to gelatin than at pH greater than 8.0. The interaction between the fibronectin and gelatin was further analysed by affinity electrophoresis in which apparent dissociation constants (Kd) of the fibronectin for gelatin were calculated, and effects of urea, 2-mercaptoethanol and temperature on the interaction were examined. The fibronectin markedly diminished its affinity to gelatin at 3 M urea to give Kd = 2.5 x 10(-6) M, which was 1000 times larger than the value without urea. The fibronectin dissociated into its monomers and the monomers diminished their affinity to gelatin in a stepwise fashion with increase in concentration of 2-mercaptoethanol. The fibronectin diminished the affinity to gelatin by elevating temperature, and van't Hoff plots of log Kd values against the reciprocal of absolute temperature (T) showed that log Kd was inversely proportional to 1/T in the range 15-50 degrees C, and the thermodynamic parameters of the standard enthalpy change, the standard free energy change and the entropy change at 37 degrees C for association of fibronectin and gelatin were all negative. At 60 degrees C the affinity of fibronectin to gelatin was not detectable.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1517339 TI - Immobilized metal ion affinity electrophoresis. A study with several model proteins containing histidine. AB - Immobilized metal ion affinity electrophoresis (IMA-Elec) is one among the many methods derived from the immobilized metal ion affinity chromatography. Two approaches for incorporating the metal ligand, were studied. One was in the form of insoluble particulate material based on Sepharose 6B and the other in the form of soluble polymer based on polyethylene glycol (PEG) 5000. Both the polymers coupled with iminodiacetate and metallized with copper or zinc were used as ligands, incorporated into soluble agarose as the electrophoretic gel. Several histidine-containing model proteins were studied with both the systems and their metal binding strengths were determined as the dissociation constants, Kd. The results clearly demonstrated that the mechanism of protein recognition by immobilized copper or zinc via the accessible histidyl residues was maintained in the IMA-Elec system. Proteins with increasing numbers of histidine residues showed increasing binding strength (lower Kd values). While this basic mechanism was conserved, the supporting polymers (Sepharose 6B and the PEG 5000) showed significant differences in the metal binding to the protein. The polysaccharide Sepharose 6B enhanced the binding strength compared with PEG 5000. The optimum electrophoretic parameters were determined to be current intensities up to 20 mA and pH ca. 7.0. At pH greater than 8.0, a significant decrease in the affinity was observed, this decrease being greater with PEG 5000 than Sepharose 6B as supporting material. PMID- 1517340 TI - Separation of monoclonal antibodies from antihapten antisera by two-dimensional affinity electrophoresis. AB - A high-resolution two-dimensional affinity electrophoresis (2D-AEP) method was developed, using capillary polyacrylamide gel (PAG) isoelectric focusing in the first and slab PAG affinity electrophoresis in the second direction. Using this method, anti-hapten antibodies were separated into a number of monoclonal antibody [immunoglobulin G (IgG)] families, each of which is composed of several IgG spots having an identical affinity to the hapten but different isoelectric points. 2D-AEP may offer a powerful tool for solving fundamental problems in immunochemistry such as antibody heterogeneity, its hapten binding specificity and antigen-dependent somatic mutation. PMID- 1517341 TI - Determination of the association constant of monovalent mode protein-sugar interaction by capillary zone electrophoresis. AB - Protein-sugar interaction was observed by capillary zone electrophoresis, using a few beta-galactose-specific lectins and lactobionic acid as protein and sugar models, respectively. The lectin peaks were retarded in a concentration-dependent manner by addition of lactobionic acid in a carrier, and association constants of monovalent mode interactions could be obtained from t1 (migration time of protein), t2 (migration time of complex, obtainable as the migration time at the plateau) and the slope of the (t-t1)-1 vs. [S]-1 plots, where t and [S] are the migration of protein in the presence of lactobionic acid and the concentration of lactobionic acid, respectively. The values for Ricinus communis agglutinin, peanut agglutinin and soy bean agglutinin at pH 6.8 were 3.3 . 10(3), 9.1 . 10(2) and 1.1 . 10(2)1 mol-1, respectively. This method required only small amounts of protein samples and was reproducible. The amount of the sugar could be minimized under the conditions that the carrier was a buffer containing the sugar whereas the electrode solutions consisted only of the buffer. PMID- 1517342 TI - Process monitoring by flow-injection immunoassay. Evaluation of a sequential competitive binding assay. AB - A new variation on the theme of flow-injection binding assays is presented, namely the sequential competitive binding assay, in which the sample containing the native antigen is first introduced into the flow system followed by a pulse of labelled antigen. The flow-injection binding assay was used in monitoring the effluent from column chromatographic separations of proteins. By applying a computer-based evaluation system, concentrations are automatically read and compensation is made for denaturation in the affinity sorbent. PMID- 1517343 TI - Biospecific interaction analysis using surface plasmon resonance detection applied to kinetic, binding site and concentration analysis. AB - A system for real-time biospecific interaction analysis using biosensor technology based on the optical phenomenon surface plasmon resonance is described. The biospecific interface is a sensor chip covered with a hydrogel matrix. One component of the interaction to be studied is immobilized covalently to the hydrogel and other interactants are passed over the chip in solution. The mass change at the sensor surface, reflecting the progress of the interaction studied, is monitored in real time. The technique, which does not require molecular labels for detection, can measure mass changes down to 10 pg/mm2. Repeated analyses can be performed on the same sensor chip. Applications shown include kinetic measurements, binding site analysis and concentration determination. PMID- 1517344 TI - Occurrence of an allosteric transition in the modification of papain with L-1 acetyl-2,3-dihydropyrrolo[2,3-b]-indole-2-carboxamide. AB - When papain was reacted with L-1-acetyl-2,3-dihydropyrrolo[2,3-b]indole- 2 carboxamide at pH 8.0, inactivation occurred accompanied by modification of Cys 25 in the active site. Plots of pseudo first-order rate constants against the reagent concentrations yielded an anomalous sigmoidal curve, suggesting that papain responded to this reagent in an allosteric manner. This is supported by the fact that the presence of a moderate concentration (a twenty-fold molar excess) of N alpha-acetyl-L-tryptophanamide over papain accelerated the inactivation. PMID- 1517345 TI - Specific assay for endotoxin using immobilized histidine, Limulus amoebocyte lysate and a chromogenic substrate. AB - The Limulus amoebocyte lysate (LAL) test is inhibited or enhanced by many substances. In order to overcome this problem, a specific endotoxin assay method using a membrane filter unit, a chromogenic LAL reagent, and immobilized histidine (which is a specific adsorbent for endotoxins) was developed. Endotoxins are quantitatively adsorbed on immobilized histidine. The adsorbed endotoxins are separated from LAL-inhibiting or -enhancing substances by the membrane filter unit, and their activities are directly assayed with the LAL reagent in a filter cup without any inhibition or enhancement. The reproducibility and the accuracy of this method are high. This new endotoxin assay method using immobilized histidine can be used for the determination of endotoxins in a solution containing LAL-inhibiting or -enhancing substances such as amino acids and antibiotics, as an alternative to the more common gel-clot technique. PMID- 1517346 TI - Use of various types of column reactors for flow-injection analysis. AB - Two or three different kinds of immobilized enzymes can be aligned in a minireactor so that sequential enzymatic reactions are carried out from upstream to downstream during flow-injection analysis. A lactate oxidase-catalase reactor, used as precolumn for removing pre-existing lactate in serum before the lactose dehydrogenase (LDH) reactions, was useful for the determination of serum LDH activity, which did not require any blank correction. A sequential glutamate dehydrogenase-glutamate oxidase reactor was also useful for a novel chemiluminometric determination of ammonia. On the other hand, a co-immobilized creatininase-creatinase-sarcosine oxidase reactor, in spite of containing creatininase which catalyses the reversible reaction, was the most efficient for the determination of serum creatinine. PMID- 1517347 TI - Study of high-affinity interactions by quantitative affinity chromatography. Analytical expressions in terms of total ligand concentration. AB - Analytical expressions are derived for the description of ligand-facilitated and ligand-retarded desorption of partitioning solute in terms of total ligand concentration in quantitative affinity chromatography. Their application is then illustrated by consideration of results from recycling partition equilibrium studies of the heparin-facilitated desorption of thrombin from heparin-Sepharose, and of the competition between methyl-alpha-D-mannoside and p-nitrophenyl-alpha-D mannoside for concanavalin A immobilized on CPG-170. Finally, published frontal affinity chromatographic data for the NADH-dependent elution of rabbit muscle lactate dehydrogenase from oxamate-Sepharose are reanalysed using these equations to demonstrate the characterization of a system reflecting the binding of a solute-ligand complex to an affinity matrix. This investigation extends the scope of quantitative affinity chromatography to include not only the study of solute ligand interactions governed by larger binding constants but also the characterization of interactions in which the partitioning solute and ligand are both macromolecular, and eliminates the need for prior dialysis to establish the free ligand concentration required for application of earlier analytical expressions. PMID- 1517348 TI - Recent developments in quantitative affinity chromatography. AB - This review surveys developments during the past decade in the use of quantitative affinity chromatography as a means of evaluating equilibrium constants for solute-ligand and solute-matrix interactions. Topics include allowance for multivalency of the partitioning solute, removal of the myth that highly substituted affinity matrices are unsuitable for zonal quantitative affinity chromatography, adaptation of the technique to allow characterization of high-affinity interactions and the application of quantitative affinity chromatography theory to the characterization of biospecific adsorption phenomena in cellular systems. PMID- 1517349 TI - Base-atom recognition in protein adsorption to alkyl agaroses. AB - The three proteins phosphorylase b, calmodulin and fibrinogen are adsorbed onto thioalkyl derivatives of Sepharose much more strongly than onto gels carrying the same alkyl residue coupled via a carbamate linkage. This enhancement of binding onto alkyl-S-Sepharoses compared with alkyl-N-agaroses is not primarily due to an increase in the extent of conformational changes of the proteins occurring on the gel surface. This can be shown in experiments with the tripeptide Trp-Trp-Trp. The Trp tripeptide is also adsorbed with a much higher affinity to butyl-S Sepharose than to butyl-N-Sepharose, showing that the primary interaction between the immobilized alkyl residue and the amino acids of the protein is decisive for adsorption. A model stressing the strong influence of an atom or a group of atoms at the base of an immobilized alkyl residue is described as "base-atom recognition". PMID- 1517350 TI - Determination of maleic hydrazide residues in cured tobacco by gas chromatography. AB - A rapid and sensitive method for measuring maleic hydrazide (6-hydroxy-2H pyridazin-3-one) residues in cured tobacco is described. A mixture of free and bound maleic hydrazide is extracted with hydrochloric acid in which maleic hydrazide glycoside is simultaneously hydrolysed. The free maleic hydrazide obtained is methylated using dimethyl sulphate and the derivative is partitioned into chloroform and determined by capillary gas chromatography using a nitrogen phosphorus detector. The limit of detection of maleic hydrazide is 5 ppm. PMID- 1517351 TI - Separation of non-steroidal anti-inflammatory agents using supercritical fluid chromatography. AB - Supercritical fluid chromatography (SFC) was investigated for the separation of non-steroidal anti-inflammatory agents (NSAIs). Three different stationary phases (SB-methyl-100, SB-biphenyl-30, and SB-cyanopropyl-50) were compared for the separation of the compounds. Baseline separation of a flufenamic acid, mefenamic acid, fenbufen and indomethacin mixture was achieved on the SB-biphenyl-30 column using a pressure gradient. A mixture containing flufenamic acid, mefenamic acid, acetylsalicylic acid, ketoprofen and fenbufen and another mixture containing ibuprofen, fenoprofen, naproxen, ketoprofen and tolmetin were well separated on the SB-cyanopropyl-50 column using pressure gradients. Typical analysis time for a mixture of NSAIs on the biphenyl or cyanopropyl column was approximately 20-25 min. Application of the method using the biphenyl column to the determination of NSAIs present in selected commercial dosage forms was demonstrated. PMID- 1517352 TI - Active respiratory syncytial virus purified by ion-exchange chromatography: characterization of binding and elution requirements. AB - Two viruses, respiratory syncytial virus (RSV) and vesicular stomatitis virus (VSV) were used to evaluate viral purification by an affinity resin column (Matrex Cellufine Sulfate (MCS); Amicon Division, WR Grace & Co.). Viable RSV was purified significantly from crude cell lysate by a single pass through a column containing the anionic MCS resin. Most cell protein and albumin eluted from the MCS resin with phosphate buffered saline (PBS) but RSV eluted at high ionic strength, i.e., greater than or equal to 0.6 M NaCl. Further purification was possible by sucrose step gradient centrifugation. The RSV prepared by column purification or by column plus sucrose gradient separation was both intact and infective. RSV and pure samples of VSV were used to optimize ionic strength and salts for elution from the MCS column: 0.8 M NaCl removed most of the viral protein. The capacity of the MCS gel for RSV or VSV was found to be about 0.6-0.8 mg viral protein per ml of hydrated resin. Detergent-solubilized viral membrane proteins bound to the MCS resin in 0.145 M NaCl and eluted with higher salt concentrations. Thus, this resin also may be a useful aid for relatively gentle purification of these proteins. PMID- 1517353 TI - Detection of African horsesickness virus in infected spleens by a sandwich ELISA using two monoclonal antibodies specific for VP7. AB - A sandwich enzyme-linked immunsorbent assay (ELISA) for rapid detection of African horsesickness virus (AHSV) in infected spleens or cell culture supernatant was developed. This method uses two monoclonal antibodies (MAbs) which recognize two non-overlapping epitopes of the major core protein (VP7) to coat the solid phase, and one labeled with biotin as second antibody. This ELISA was evaluated for its ability to detect AHSV in infected spleens resulting in a sensitivity of 97.4% and a specificity of 100% compared with virus isolation in cell culture, and can be used for the detection of the nine different AHSV serotypes. PMID- 1517354 TI - Clinical review 37: Endocrine treatment of prostate cancer. PMID- 1517355 TI - Hyperprolactinemia and osteopenia. PMID- 1517356 TI - Progressive trabecular osteopenia in women with hyperprolactinemic amenorrhea. AB - Reductions in cortical and trabecular bone mass have been documented in young women with hyperprolactinemic amenorrhea. It is unknown whether trabecular osteopenia is progressive or reversible with treatment of hyperprolactinemia. In addition, it is not known whether clinical or hormonal variables can predict trabecular bone density (BD) changes. Therefore, we investigated prospectively trabecular BD by computed tomography in 52 hyperprolactinemic women and 41 controls. The mean follow-up interval was 1.8 +/- 0.1 (SEM) yr. Patient groups were defined as follows: group 1, amenorrhea during the entire study; group 2, restoration of menses during the study by treatment of hyperprolactinemia; group 3, regular menses despite hyperprolactinemia, with no history of prior amenorrhea; group 4, history of prior amenorrhea, but menses restored with treatment of hyperprolactinemia before study entry; and group 5, oligomenorrhea. Groups 1, 2, and 4 had significant (P = 0.0006) initial spinal osteopenia [mean BD 141 +/- 7 (SEM), 144 +/- 9, and 151 +/- 5 mg/cc K2HPO4, respectively] compared with controls or with group 3 (170 +/- 4 and 173 +/- 8 mg/cc K2HPO4, respectively). Group 5 had an initial mean BD which was midway between that of the amenorrheic and eumenorrheic women (156 +/- 13 mg/cc K2HPO4). Group 1 had a significant (P = 0.04) decrease in mean BD to 132 +/- 8 mg/cc K2HPO4 over 1.7 +/- 0.2 yr, with BD in 42% of the group more than 2 SD below the control mean at the final study point. The mean BD in group 2 increased to 155 +/- 9 mg/cc K2HPO4, approaching significance (P = 0.07) when compared with the initial BD. Five of the nine patients in this group (56%) had an increase in BD greater than the variation expected for the computed tomography technique. However, 44% of the group 2 patients had a spinal BD which remained more than 1 SD below the normal mean. There was no change in BD in the other groups.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1517357 TI - A longitudinal analysis of premenopausal bone loss in healthy women and women with hyperprolactinemia. AB - In this report we describe longitudinal measurements of forearm and spinal bone mineral in healthy women and women with hyperprolactinemia. One hundred and ten women underwent yearly assessment of forearm and spinal bone mineral by single photon absorptiometry and computed tomography for an average of 4.7 yr. At entry into the study, women with hyperprolactinemic amenorrhea had 21% lower spinal bone mineral and 2.5% lower forearm bone mineral than healthy premenopausal women. Despite decreased estradiol levels (31 +/- 23 pmol/L), spinal bone in women with hyperprolactinemic amenorrhea did not change over time (+0.08%/yr; P = 0.89). In contrast, spinal bone in healthy women with regular menses (mean age, 34.6 +/- 6.6 yr) decreased significantly (1.7%/yr; P = 0.01). Cortical bone in the forearm did not change in either group. The hyperprolactinemic subjects had higher body mass index (28 +/- 6 vs. 24 +/- 4 kg/m2) and serum testosterone (0.5 +/- 0.2 vs. 0.39 +/- 0.16 pmol/L) than control subjects, but neither parameter correlated with bone loss. Although 64% of the hyperprolactinemic subjects had serum estradiol levels below 30 pmol/L, there was no correlation between estradiol or duration of amenorrhea and bone loss. Women with normal PRL levels and regular menses 3-9 yr after treatment of hyperprolactinemia had significantly lower spinal bone mineral (147 +/- 28 mg/mL) than healthy premenopausal women (169 +/- 29 mg/mL) and showed no change in spinal bone (+0.3%/yr; P = 0.67) over 5 yr. Despite significant hypoestrogenemia, women with hyperprolactinemic amenorrhea did not evidence a rapid decline in spinal bone. Restoration of gonadal function was not associated with normalization of bone mineral. The bone loss that accompanies hyperprolactinemia is not comparable to that which occurs after oophorectomy or menopause. These findings raise important questions about the importance of osteopenia as an indication for treatment of hyperprolactinemic amenorrhea. PMID- 1517358 TI - Role of the hypothalamo-pituitary function in the hypoandrogenism of healthy aging. PMID- 1517359 TI - Attenuation of luteinizing hormone secretory burst amplitude as a proximate basis for the hypoandrogenism of healthy aging in men. AB - To evaluate the impact of healthy aging on specific features of endogeneous LH secretion and clearance, we applied deconvolution analysis to 24-h serum immunoradiometric LH concentration series obtained in normal men whose ages ranged from 21-73 yr. Deconvolution analysis was employed to quantitate the number, amplitude, duration, and mass of individual LH secretory bursts underlying the serum LH concentration profiles, and simultaneously estimate the half-life of LH in individual men. Plasma total and free testosterone and estradiol concentrations and body mass index (a measure of relative adiposity) were studied as possible significant covariates of age and LH secretion. We found that age was a negative determinant of LH secretory burst amplitude (r = -0.519, P = 0.013), and a positive predictor of LH secretory burst frequency (r = +0.435, P = 0.043) and basal LH secretory rates (r = +0.486, P = 0.029). Increasing age also correlated positively with LH secretory burst half-duration (duration of the secretory event at half-maximal amplitude, r = +0.656, P less than 0.001). In contrast, age did not relate to daily pulsatile LH production rate, the mass of LH secreted per burst, or the mean (24-h) serum concentration of immunoradiometric LH. Age correlated negatively with serum free testosterone (r = -0.622, P = 0.0034) but not estradiol concentrations. The serum free testosterone concentration also declined significantly with increasing body mass index (r = 0.519, P = 0.023). Although there were strong combined effects of age, body mass index, and LH secretory burst amplitude on serum free testosterone concentrations (P = 0.0006, multi-r value 0.820), LH secretory burst amplitude was the most prominent single determinant of blood androgen concentrations. PMID- 1517360 TI - The results of various modalities of treatment of well differentiated thyroid carcinomas: a retrospective review of 1599 patients. AB - This study analyzed the impact of prognostic variables of age, sex, histopathological diagnosis, extent of disease at diagnosis, and surgical intervention on well differentiated thyroid carcinoma and how surgical treatment, radioactive iodine, and radiotherapy influence the patients' outcomes. There have been 1599 patients with well differentiated thyroid cancer treated and followed at the University of Texas M.D. Anderson Cancer Center from 1948 to 1989. The median follow-up for all patients was 11.0 yr, with the maximum follow-up being 43 yr and the minimum follow-up being 1 yr. The patients were predominantly female (2.3:1), with papillary (81%) and intrathyroidal carcinomas (42%) at the time of diagnosis. Sixty-six percent of the patients had a total thyroidectomy, 7% received external radiotherapy, and 46% had radioactive iodine as part of the treatment of the original disease; the overall recurrence rate was 23%, and the death rate was 11%. This study showed that treatment with radioactive iodine was the single most powerful prognostic indicator for increased disease-free interval (P less than 0.001) and that its use significantly increased survival as well. No benefit was obtained from treatment with external radiotherapy. Children had the best overall survival, but of the adult patients, females who had intrathyroidal papillary disease treated with total thyroidectomy, who had been given radioactive iodine, and whose disease had been diagnosed between 20-59 yr of age had the best prognosis. PMID- 1517361 TI - 3,3',5'-Triiodothyronine inhibits collagen-induced human platelet aggregation. AB - To clarify further the activity of rT3, we examined the effect of rT3 on collagen induced platelet activation as reflected by aggregation, serotonin release, and protein phosphorylation. rT3, T4, T3, and triiodothyroacetic acid inhibited collagen-induced platelet aggregation and serotonin release from platelets in a dose-dependent manner. However, thyronine did not inhibit collagen-induced platelet aggregation. The concentration at which rT3 inhibited by 50% collagen induced platelet aggregation was 30 +/- 4 (mean +/- SE) mumol/L. rT3, T4, and T3 did not differ significantly in their abilities to inhibit platelet aggregation. Moreover, rT3 inhibited collagen-induced phosphorylation of the 20-kilodalton protein (myosin light chain) in platelets. In contrast, rT3 did not inhibit 12-O tetradecanoylphorbol 13-acetate (TPA)- or thrombin-induced platelet aggregation and inhibited only minimally TPA-induced 40-kilodalton protein phosphorylation. These results suggest that rT3 inhibits collagen-induced platelet activation by inhibiting the activity of myosin light chain kinase and that it may be interesting to investigate some kinds of activity of rT3. PMID- 1517362 TI - Effects of iodine on thyroid status of fetus versus mother in treatment of Graves' disease complicated by pregnancy. AB - To investigate the effect of maternal iodine therapy for Graves' disease on fetal thyroid, we examined serum free T4 (FT4) and TSH levels in the fetus vs. those in the mother. Patients who were severely thyrotoxic were not included. Cord and maternal sera were tested at delivery in 35 patients with Graves' disease treated with iodine alone during pregnancy (6-40 mg daily). At the initiation of therapy, the mothers were at 11-37 weeks gestation, and FT4 levels ranged from 28.3-65.8 pmol/L. At delivery, maternal FT4 values ranged from 9.3-42.0 pmol/L, slightly above normal in 22 of the 35 mothers and normal in the other 13. Fetal FT4 levels were above the normal range occurred significantly less often than maternal levels (2 in 35; P less than 0.001), and no fetus had FT4 below normal. In the 13 mothers with normal FT4 levels, all fetal FT4 levels were normal; the fetal TSH level was above normal in 1 and normal in the remainder. A significant correlation was found between cord and maternal FT4 levels (P less than 0.05). In 12 of the 35 mothers, FT4 levels rose after a transient fall during iodine administration. The correlation of cord FT4 and maternal FT4 was closer when these 12 cases were excluded (P less than 0.001). Neither the dose of iodine nor the duration of therapy correlated with thyroid function in fetuses or mothers. Fetal TSH binding inhibitory antibody values strongly correlated with maternal TSH binding inhibitory antibody values (P less than 0.001). These findings indicate that 1) in the treatment of hyperthyroidism due to Graves' disease, iodine seldom if ever exposes the fetus to the risk of hypothyroidism; 2) the fetal thyroid is influenced by the same stimulatory and inhibitory factors as the maternal thyroid; and 3) escape from the inhibitory effects of iodine occurs less often in fetuses than in mothers, which may account at least in part for the lower thyroid status in the fetus compared to that in the mother. PMID- 1517363 TI - Effect of hyperthyroidism on the transit of a caloric solid-liquid meal through the stomach, the small intestine, and the colon in man. AB - Gastric emptying, mouth-to-cecum transit, and whole gut transit of a solid-liquid meal was measured in 20 hyperthyroid patients and in 30 control subjects by using scintigraphic techniques, the hydrogen breath test, and stool markers. In the hyperthyroid patients predefined gastrointestinal symptoms were determined and related to gastrointestinal transit. There was no significant overall difference of gastric emptying between the hyperthyroid patients and the control subjects, whereas both mouth-to-cecum transit time (mainly reflecting small intestinal transit) and whole gut transit time (mainly reflecting large intestinal transit) were significantly accelerated in hyperthyroid patients as compared to the control subjects (P less than 0.005). Mouth-to-cecum transit in hyperthyroid patients with diarrhea tended to be more rapid than in those without diarrhea (P = 0.094) and the T3 concentrations were inversely correlated with mouth-to-cecum transit time. It is concluded that in thyrotoxicosis 1) small and large intestinal transit is accelerated, while gastric emptying remains unchanged and 2) rapid intestinal transit is likely to be one factor among others implicated in the generation of diarrhea. PMID- 1517364 TI - Vasopressin, corticotrophin-releasing factor, and pituitary adrenal responses to acute cold stress in normal humans. AB - Acute cold stress is a consistent stimulus to ACTH secretion in rats yet inhibits arginine vasopressin (AVP) in both rats and humans. We have studied the interrelationships of AVP, corticotrophin-releasing factor, and atrial natriuretic factor (ANF) in the hypothalamo-pituitary-adrenal response to acute cold stress in normal humans. Six healthy male volunteers deprived of food and fluid for 6 h, and minimally clothed, were studied in the early afternoon. After a 30-min period at 22 C, subjects were exposed to cold stress (4 C for 30 min), followed by a 30-min equilibration period at 22 C. By the end of the period of cold exposure there was a fall in plasma volume of 7.8 +/- 1.4% (mean +/- SEM), a significant increase in both systolic blood pressure (P = 0.0001) and in plasma norepinephrine level (P = 0.0001), but no change in plasma epinephrine or in plasma ANF. Plasma AVP levels fell significantly (P less than 0.01) to reach a nadir at 5-10 min after cold exposure before returning to baseline levels. A significant fall in plasma cortisol levels occurred during the first 15 min of the baseline period and remained stable thereafter. No significant changes in plasma corticotrophin-releasing factor or ACTH occurred. These results suggest that cold inhibition of AVP release, presumably via afferent baroreceptor pathways, may act to reduce the response of the corticotrophs to a potentially noxious stimulus. Inhibition of AVP and/or ACTH during acute cold exposure are not dependent upon an increase in plasma ANF. PMID- 1517365 TI - Activin-A inhibits progesterone production by macaque luteal cells in culture. AB - Since inhibin is produced during the luteal phase of the menstrual cycle in women and nonhuman primates, the primate corpus luteum (CL) may be a local site of inhibin/activin action. This study was designed to determine whether inhibin or activin altered steroidogenesis by macaque luteal cells in vitro. Luteal cells were obtained by enzymatic dispersion of CL from rhesus monkeys at midluteal phase of the menstrual cycle. Cells (2 x 10(4)/0.2 mL) were cultured in wells coated with extracellular matrix from bovine corneal endothelial cells in Dulbecco's modified Eagle's medium/F-12 medium (1:1 vol/vol) + insulin (2 ng/mL), transferrin (5 ng/mL), H2SeO3 (0.25 nmol), and aprotinin (10 micrograms/mL). Various concentrations (0-400 ng/mL) of recombinant human-inhibin-A, recombinant human-activin-A or human CG (hCG) (100 ng/mL; CR123) alone or in combination with inhibin or activin were added to the culture media (n = 5 Exp). Media were changed daily for 4 days and progesterone (P) concentrations were determined by RIA. Inhibin exposure did not alter P levels compared to that of control (untreated) cultures. In contrast, activin (10-400 ng/mL) suppressed P production (P less than 0.05) below controls and inhibin-treated cultures by days 3 and 4. Exposure to hCG increased P levels throughout culture (9 x control levels by day 4; P less than 0.05). hCG-stimulated P production was unaltered by inhibin, whereas activin (50-400 ng/mL) reduced (maximal inhibition of 40%; P less than 0.05) hCG-stimulated P production by day 4 of culture. Cell number on day 4 was not altered by any dose of inhibin or activin, but the number of cells staining for 3 beta-hydroxysteroid dehydrogenase was reduced (P less than 0.05) by 32.9 +/ 2.6% in activin-treated cultures. Since P levels declined during culture in all treatment groups, in a second series of experiments (n = 4), luteal cells were cultured for 4 days with or without hCG (100 ng/mL) and low density lipoprotein (LDL; 100 micrograms/mL) +/- 0-400 ng activin/mL. P production in the presence of hCG+LDL was greatly enhanced compared to other treatment groups and was sustained during days 2-4 of culture. Activin at doses of 50-400 ng/mL suppressed (maximal inhibition of approximately 35%; P less than 0.05) hCG+LDL-stimulated P production on days 3 and 4. These results suggest that the primate CL is a target for activin action to suppress luteal cell activities, including gonadotropin regulated, lipoprotein-mediated steroidogenesis. PMID- 1517366 TI - Fat mass is an important determinant of whole body bone density in premenopausal women but not in men. AB - We recently reported that total body fat mass is the principal determinant of bone density in normal postmenopausal women. We have now reexamined the relationships among these variables and lean mass in 68 healthy premenopausal women and 51 men. Areal bone density (BMD), fat mass, and lean mass were measured in total body scans by dual-energy, x-ray absorptiometry. In women, BMD was correlated with weight (r = 0.69), fat mass (r = 0.60), and lean mass (r = 0.55). In men, the respective correlations were 0.56, 0.26 (NS), and 0.51. Multiple regression analysis confirmed a codependence of female BMD on fat and lean masses, whereas male BMD was related only to lean mass. Because BMD is an areal not volumetric density, it is dependent on body size. The analysis was therefore repeated using BMD/height as an index of "true" density. Correlations with fat mass were little changed but those with lean mass were reduced (women) or eliminated (men). By multiple regression, female BMD/height was related to fat mass alone, and in men there was a borderline effect of fat (P = 0.05) but none of lean mass. As a second method to exclude a scale artifact, fat mass was expressed as percent body weight. It was related to BMD (r = 0.48) only in women. It is concluded that bone density is closely related to fat mass in premenopausal women, but less so in men. In both sexes, apparent relationships between BMD and lean mass are artifacts attributable to the use of areal density (which is dependent on body size) as a surrogate for volumetric density. The mechanism of this fat-bone density relationship is an important question to be addressed in bone biology. PMID- 1517367 TI - Rapid stimulation of human chorionic gonadotropin secretion by interleukin-1 beta from perifused first trimester trophoblast. AB - Placental trophoblast has been implicated as a major source of interleukin-1 beta (IL-1 beta), a cytokine that mediates immunological responses in the body. This study evaluated the effect of IL-1 beta on hCG secretion from 8- to 12-week-old placental trophoblast. Physically dissociated trophoblast cells collected from multiple placentae were cultured on carrier beads and loaded into chambers in a perifusion system. Medium was perifused through the chambers, and effluent was collected and assayed for hCG. Basal hCG secretion was not dependent on exogenous IL-1 beta or GnRH, but varied between mixed placental preparations and increased with duration of culture. Therefore, hCG secretion was expressed as a percentage of mean basal hCG secretion for any given chamber. IL-1 beta (10(-9) M) stimulated a rapid and transient hCG secretory response. hCG release increased by approximately 150% (P less than 0.05; n = 5) in response to the cytokine, but lower concentrations (10(-10) and 10(-11) M) were ineffective (P greater than 0.05; n = 3 each). GnRH stimulated hCG secretion by approximately 80% (P less than 0.05; n = 6). The hCG secretory profiles in response to IL-1 beta and GnRH were similar. Combined treatment with equimolar (10(-9) M) IL-1 beta and GnRH increased hCG secretion by approximately 150% (P less than 0.05; n = 5), stimulating hCG secretion as effectively as either hormone alone (P greater than 0.05). The stimulatory effect of GnRH on hCG secretion was blocked by the concomitant presence of a GnRH antagonist, Nal-Glu-GnRH (P less than 0.05; n = 5). However, simultaneous treatment with IL-1 beta and Nal-Glu-GnRH did not affect IL-1 beta-stimulated hCG secretion (100.5 +/- 3.6 vs. 162.9 +/- 10.2%; P less than 0.05; n = 7). The data suggest that IL-1 beta and GnRH stimulated a near-maximal physiological hCG secretory response, possibly through different receptor types. Alternatively, these two hormones may share a common signal transduction pathway, or IL-1 beta may influence a step distal to the coupling of GnRH to its receptor in the placental trophoblast. PMID- 1517368 TI - Lipolysis and gluconeogenesis from glycerol are increased in patients with noninsulin-dependent diabetes mellitus. AB - The rate of lipolysis (glycerol Ra), gluconeogenesis from glycerol, and its contribution to overall hepatic glucose production (glucose Ra) were determined in 10 patients with noninsulin-dependent diabetes mellitus (NIDDM) [body mass index (BMI) 27.2 +/- 1.0 kg/m2, fasting plasma glucose 10.3 +/- 1.2 mmol/L], and in 6 matched control subjects (BMI 27.3 +/- 1.1 kg/m2, fasting plasma glucose 5.3 +/- 0.3 mmol/L) using infusions of [3-3H]glucose (0-600 min) and [U-14C]glycerol (360-600 min). Glycerol Ra was increased in the patients with NIDDM (120 +/- 16 mumol/m2.min) compared to the normal subjects (84 +/- 9 mumol/m2.min, P less than 0.05). Gluconeogenesis from glycerol was 1.7-fold higher in the patients (96 +/- 16 mumol/m2.min) than in the normal subjects (56 +/- 10 mumol/m2.min, P less than 0.05), and explained 9 +/- 1% and 7 +/- 1% (NS) of total glucose Ra in patients with NIDDM and normal subjects, respectively. To determine whether these abnormalities are more pronounced in overweight patients with NIDDM, glucose and glycerol Ra were also determined in 5 obese patients with NIDDM (BMI 36.4 +/- 1.0 kg/m2, fasting plasma glucose 11.3 +/- 1.3 mmol/L). Glycerol Ra (154 +/- 26 mumol/m2.min) was again higher than in the normal subjects (P less than 0.05) but not different from that in the less obese patients with NIDDM. The rate of gluconeogenesis from glycerol (159 +/- 20 mumol/m2.min) was significantly higher in the obese than in the less obese patients with NIDDM (P less than 0.05) but its contribution to total glucose Ra (10 +/- 1%) was similar to that in the less obese patients with NIDDM. When all data were analyzed together, gluconeogenesis from glycerol (r = 0.57, P less than 0.01) but not lipolysis (r = 0.02, NS) correlated with the percentage of lipolysis diverted toward gluconeogenesis suggesting that the rate of gluconeogenesis from glycerol is regulated by intrahepatic mechanisms rather than by glycerol availability. Neither the rate of lipolysis nor the rate of glycerol gluconeogenesis correlated with BMI, serum triglyceride, or insulin concentrations. We conclude that gluconeogenesis from glycerol is increased in patients with NIDDM. This increase appears to be the consequence of both accelerated lipolysis and increased intrahepatic conversion of glycerol to glucose. PMID- 1517369 TI - Defect in insulin action on expression of the muscle/adipose tissue glucose transporter gene in skeletal muscle of type 1 diabetic patients. AB - Recently several members of the glucose transporter family have been identified by molecular cloning techniques. We determined the effect of a 4-h insulin infusion on the expression of the muscle/adipose tissue (GLUT-4) glucose transporter mRNA and protein in 14 insulin-treated type 1 diabetic patients and 15 matched nondiabetic subjects. GLUT-4 mRNA and protein concentrations were determined in muscle biopsies taken before and at the end of the insulin infusion during maintenance of normoglycemia. In response to insulin, muscle GLUT-4 mRNA increased in the nondiabetic subjects from 24 +/- 3 to 36 +/- 4 pg/microgram RNA (P less than 0.001) but remained unchanged in the insulin-resistant diabetic patients (24 +/- 2 vs. 26 +/- 2 pg/microgram RNA, before vs. after insulin). The glucose transporter protein concentrations were similar in the basal state and decreased by 21 +/- 7% (P less than 0.02) in the normal subjects but remained unchanged in the diabetic patients. The increase of the GLUT-4 mRNA and the decrease in the GLUT-4 protein correlated with the rate of glucose uptake [correlation coefficient (r) = -0.55, P less than 0.01, and r = -0.44, P less than 0.05, respectively]. We conclude that the insulin response of both the GLUT 4 glucose transporter mRNA and protein are absent in skeletal muscle of insulin resistant type 1 diabetic patients. Thus, impaired insulin regulation of glucose transporter gene expression can be one of the underlying mechanisms of insulin resistance in type 1 diabetes. PMID- 1517370 TI - Maternal and neonatal thyroid function at birth in an area of marginally low iodine intake. AB - Thyroid function was evaluated in cord serum of healthy full-term newborns and compared to that of mothers immediately after parturition. The study was carried out in an area without overt iodine deficiency, but with a marginal iodine supply (less than 100 micrograms/day in 80% of women). The aim of the study was to delineate the interrelationships between the thyroid statuses of mother and child at birth. Maternal thyroid function was characterized at delivery by relative hypothyroxinemia; increased T3/T4 ratios, indicating preferential T3 secretion; slightly increased TSH levels within the normal range in 97% of women; increased serum thyroglobulin (TG) values, which were above normal in 60% of women; and also goiter formation in almost 10% of women. The findings indicated glandular stimulation and confirmed our earlier reports that pregnancy constitutes a stress for the maternal thyroid economy, enhanced by the limited availability of iodine in the diet. By contrast, newborns showed a strikingly distinct pattern: there was no relative hypothyroxinemia and free T4 levels were significantly higher than in the respective mothers (19.4 vs. 14.7 pmol/L; P less than 0.001). In spite of these differences, however, mean neonatal TSH and TG levels were significantly higher than maternal values, respectively 6.0 vs. 1.9 mU/L for TSH (P less than 0.001) and 70 vs. 40 micrograms/L for TG (P less than 0.001). Furthermore, neonatal TG and TSH levels increased in parallel and were highly correlated with maternal data, suggesting a regulatory link between both thyroid economies. The results suggested that the common regulatory link is the limited availability of the iodine supply. In conclusion, the present study demonstrates that even in conditions with a marginally low iodine intake, pregnancy constitutes a stimulus for both the maternal and newborn thyroids. Changes in both groups are associated and the abnormalities in TSH and TG are amplified in the newborns. The TSH and TG alterations at birth in full-term healthy newborns, associated with similar alterations in maternal thyroid function, provide evidence for a common stimulatory factor, relative iodine deficiency. The data emphasize the hypersensitivity of neonatal thyroid function to marginal iodine deficiency and point to the need to increase the iodine supply in groups at risk, such as women during pregnancy, and also newborns in the perinatal period. PMID- 1517371 TI - Regulation of pulsatile growth hormone secretion by fasting in normal subjects and patients with acromegaly. AB - In acromegaly, GH hypersecretion occurs despite elevated insulin-like growth factor-I (IGF-I) levels, implying defective IGF-I feedback. To study the possible mechanisms of defective IGF-I negative feedback in acromegaly, we assessed parameters of pulsatile GH secretion during fasting-induced decrease in plasma IGF-I. Seven patients with active acromegaly and six normal controls were fasted for 6 days and GH secretory profiles were obtained by frequent (every 10 min) blood sampling for 24 h and analyzed by Cluster. Fasting resulted in similar decreases in IGF-I, body weight, and blood glucose levels, and increases in free fatty acid and beta-hydroxybutyrate in all subjects. Normal subjects showed increases in 24-h total and pulsatile GH production, GH pulse frequency, maximal pulse amplitude, interpulse and nadir levels, implying suppression of hypothalamic somatostatin secretion and increase in GH-releasing hormone (GHRH) pulse frequency. In acromegalic patients, GH (and, by inference, GHRH) pulse frequency was unchanged. Three patients had increases in GH production, interpulse, and nadir levels similar to the normals while the other four had no change or paradoxical decreases in these parameters. Percentage change in GH production was highly correlated with percentage change in interpulse and nadir levels in both normals and patients. Mean GH response to GHRH (0.33 micrograms/kg iv) did not change significantly in any group as a result of fasting. Our data suggest that in healthy humans IGF-I negative feedback on GH secretion involves suppression of GHRH pulse frequency. GH (and, by inference, GHRH) pulse frequency is resistant to decrease in IGF-I in acromegaly, suggesting that lowered sensitivity of GHRH neurons to IGF-I may be the mechanism of high GH pulse frequency in this disease. PMID- 1517372 TI - Differing responses of plasma bioactive and immunoreactive follicle-stimulating hormone and luteinizing hormone to gonadotropin-releasing hormone antagonist and agonist treatments in postmenopausal women. AB - Plasma bioactive (B) and immunoreactive (I) FSH and LH were measured every 10 min for 8 h in the same postmenopausal women in a three-phase study: 1) during normal pulsatile gonadotropin secretion (basal study; n = 8), 2) 8 h after a single injection of a GnRH antagonist (5 mg Nal-Glu, sc; n = 5), and 3) 21 days after a GnRH agonist injection (D-Trp6, 3.75 mg depot preparation, im; n = 7). I-FSH and I-LH were measured by monoclonal antibody immunoradiometric assays. B-FSH and B LH were measured in selected samples with the immature rat granulosa cell and mouse interstitial cell assays, respectively. Significant pulsatility of B- and I FSH and LH was demonstrated in the basal samples, but only the B/I ratio of LH was slightly elevated within the secretion peaks. After GnRH antagonist treatment, I-FSH decreased from a mean pretreatment level of 55.7 +/- 7.8 IU/L by 26% (P less than 0.001), and B-FSH from 313.8 +/- 61.9 IU/L by 44% (P less than 0.01). The B/I ratio decreased from 6.4 +/- 1.7 to 4.5 +/- 1.0 (P less than 0.05). After agonist treatment, the I- and B-FSH levels decreased by 92% and 83% (P less than 0.0001), respectively, but the B/I ratio increased to 17.3 +/- 4.7 (P less than 0.05). The concentrations of I- and B-LH decreased by 75% and 80%, respectively (P less than 0.001), after antagonist treatment. After agonist treatment, I-LH decreased by 92%, and B-LH by 93% (P less than 0.0001). No changes in the B/I ratios of LH were found after either treatment. In conclusion, no changes were found in the quality of circulating LH during the treatments, whereas the antagonist treatment decreased and the agonist treatment increased the B/I ratio of FSH. These findings provide further evidence that the qualitative responses of FSH and LH to treatment with the same GnRH analog are different, and that the suppressive mechanisms of GnRH antagonist and agonist action on gonadotropin secretion are different. PMID- 1517373 TI - Preclinical Cushing's syndrome in adrenal "incidentalomas": comparison with adrenal Cushing's syndrome. AB - Adrenal tumors are usually diagnosed by clinical symptoms of hormone excess. The increasing use of ultrasound and computed tomography results in the detection of a substantial number of incidentally discovered adrenal tumors. Most of these tumors are nonfunctional adrenocortical adenomas, but a few cases of subclinical cortisol production in "incidentalomas" have been reported. We investigated prospectively the prevalence of autonomous cortisol production in 68 patients (44 females and 24 males, aged 25-90 yr) with adrenal incidentalomas at our institution. As a screening procedure all patients with incidentalomas underwent an overnight dexamethasone suppression test (1 mg). Patients who failed to suppress serum cortisol below 140 nmol/L (5 micrograms/dL) underwent more comprehensive studies (prolonged dexamethasone suppression test, determination of the diurnal rhythm of cortisol secretion in saliva, and CRH stimulation test). Eight patients (12% of all patients with incidentalomas; 5 females and 3 males, aged 25-71 yr) were finally identified as having cortisol-producing tumors, and the findings in these patients were compared with those of overt Cushing's syndrome in 8 patients (8 females, aged 26-50 yr) suffering from cortisol producing adrenal adenomas. The tumor size of patients with cortisol-producing incidentalomas ranged from 2-5 cm. No specific signs and symptoms of hypercortisolism were present, but arterial hypertension (seven of eight subjects), diffuse obesity (four of eight subjects), and noninsulin-dependent diabetes mellitus (NIDDM; two of eight subjects) were frequently observed. Baseline cortisol levels were in the normal to upper normal range, whereas baseline ACTH levels were suppressed in five of the eight patients. In none of the patients was serum cortisol suppressible by low dose or high dose dexamethasone. The ACTH and cortisol responses to CRH were normal in two, blunted in one, and suppressed in four patients. Unilateral adrenalectomy was performed in seven patients and resulted in temporary adrenal insufficiency in four of them. After surgery, improvement of arterial hypertension, a permanent weight loss in obese subjects, and a better metabolic control of NIDDM were noted in the majority of patients. The following conclusions were reached. Incidentally diagnosed adrenal tumors with pathological cortisol secretion in otherwise clinically asymptomatic patients are more frequently observed than previously assumed. Adrenocortical insufficiency is a major risk in these patients after adrenalectomy. After surgery, hypertension, obesity, and NIDDM may improve. Patients with asymptomatic adrenal incidentalomas, therefore, should be screened for cortisol production by means of an overnight dexamethasone suppression test. PMID- 1517374 TI - Body composition in adult growth hormone-deficient men, assessed by anthropometry and bioimpedance analysis. AB - Anthropometry and bioimpedance analysis (BIA) were used to assess body composition in 42 GH-deficient (GHD) adult males (mean age, 27.2 +/- 4.7 yr). During childhood, all patients had received GH treatment for a mean period of 8.4 +/- 3.8 yr. At the start of this study, GH therapy had been discontinued for a mean period of 7.5 +/- 4.5 yr. Eighteen patients had isolated GH deficiency (I GHD). Twenty-four patients had multiple pituitary hormone deficiencies (M-PHD), substituted adequately. Compared to age- and sex-matched controls, the sum of skinfolds measured at 7 different sites was significantly higher in I-GHD and M PHD patients [controls, 73.1 +/- 25.4 mm; I-GHD patients, 102.1 +/- 37.7 mm (P less than 0.001); M-PHD patients, 126.8 +/- 35.4 mm (P less than 0.001)]. The increase in sc fat deposition was most pronounced on the trunk, particularly in the breast and abdominal area. Total body muscle mass was significantly lower in GHD patients (P less than 0.001). In patients, body muscle mass and plasma somatomedin-C level were positively correlated (r = 0.43; P less than 0.005). Total body resistance measured by whole body BIA was significantly higher in the patient group and was negatively correlated with plasma somatomedin-C (r = -0.53; P less than 0.001). The high resistance values observed in GHD patients could only in part be explained by their lower lean body mass. The most important cause, however, was an increase in specific electrical resistance of the lean body mass (LBM), reflecting relative dehydration. We conclude that GH deficiency in adult males is associated with an increase in sc fat and a decrease in body muscle mass. In addition, there is a qualitative change in LBM. The BIA data indicate that in these patients, the hydration state of the LBM is lower than normal, due to a decrease in extracellular water. PMID- 1517375 TI - In vitro stimulation of placental progesterone production by 19-nortestosterone and C19 steroids in early human pregnancy. AB - To explore the regulatory mechanism at the critical period of the luteal placental shift, the effects of various steroids and peptides on the production of progesterone by placental explants at 7-10 weeks were studied. Androstenedione increased progesterone production 3-fold at a concentration of 1 mumol and more than 20-fold at 18 mumol. 19-Nortestosterone (1-18 mumol) stimulated progesterone production 10- to 100-fold. 5 alpha-Androstane-3 beta,17 beta diol (1-18 mumol) stimulated progesterone production about 2- to 5-fold while its 3 alpha isomer (1 6 mumol) increased it 2-fold. Estrone, estradiol, and estriol up to a concentration of 30 mumol had no effect. Dehydroepiandrosterone sulfate (to 36 mumol), androst-5-ene-3 beta,17 beta diol (1-6 mumol), 5 beta-androstane-3 alpha,17 beta diol (1-6 mumol), and dihydrotestosterone (1-12 mumol) had no effect. Cortisol and dexamethasone (up to 12 mumol), hCG (20,000 IU/L), GnRH (4 mumol), and ACTH 1-24 (20 mumol) also had no effect. Thus, of all the compounds tested, only 19-nortestosterone and, to a lesser extent, androstenedione, 5 alpha androstane-3 beta,17 beta diol, and 5 alpha-androstane-3 alpha,17 beta diol stimulated progesterone production in early pregnancy; at term, only 5 alpha androstane-3 beta,17 beta diol was stimulatory. 19-Nortestosterone was found to be less efficiently aromatized compared to other androgens; since it is also known to be present in blood from pregnant women and thought to be made in the placenta, the stimulation observed may be a paracrine effect. These observations suggest that C18 and C19 steroids may be important in the regulation of progesterone synthesis by the human placenta in early pregnancy. PMID- 1517376 TI - Genetic linkage analysis in familial benign hypercalcemia using a candidate gene strategy. I. Studies in four families. AB - Despite extensive study since the first report of familial benign hypercalcemia (FBH, or hypocalciuric hypercalcemia) in 1972, there is no evidence of the specific abnormal gene product. FBH is highly suitable for either a candidate gene or a reverse genetics approach to localizing the genetic abnormality, because it is inherited in an autosomal dominant pattern, is highly penetrant, does not affect survival, and can be diagnosed in families with readily available measurements. Importantly, several candidate genes have been cloned and mapped. Therefore, we collected blood samples and extracted leukocyte DNA from 94 members of 4 families with well documented FBH (44 affected, 45 unaffected, and 5 unclassifiable). We digested the DNA samples with various restriction endonucleases, conducted standard Southern blotting, and searched for restriction fragment length polymorphisms for the following candidate genes (probe names in parentheses): multiple endocrine neoplasia (MEN) type 1 (pMCMP.1, pHBI59, p3C7, and pTHH26), MEN 2a (MCK2 and cTB14.34), basic fibroblast growth factor (pHFL1 7), (Ca2+,Mg2+)ATPase isoform 4 (hPMCA4), membrane Na/Ca exchanger (cNC28 M-A), PTH (pPTH-LF), and calbindin-D28K (pSKCalb). In addition, we used the anonymous variable number tandem repeat marker pYNH24 to verify pedigree structures by excluding misinheritances. Data were analyzed using the Linkage program. For none of the genes was there significant linkage with the FBH trait; logarithm of odds scores ranged from -1.3 to -26.0 at a recombination fraction of 0.001, and from 0.6 to -5.6 at a recombination fraction of 0.10. We conclude that FBH is unrelated to the MEN syndromes and is not caused by mutations in any of the calcium-regulating or -binding proteins or growth factors studied thus far. PMID- 1517377 TI - Growth hormone-binding proteins of human serum: developmental patterns in normal man. AB - The binding of GH by a low affinity binding protein (LA-BP) was measured from birth into adulthood and compared with binding of a high affinity binding protein (HA-BP) in human serum. Pooled serum samples for each year of age from birth to 16.5 yr were formed from 2500 separate samples and assayed for both binding proteins using a Sephadex chromatographic method. Individual samples in this age range and those from adults were assayed in a similar manner. Binding of [125I]GH was minimal by both binding proteins in cord blood (binding by LA-BP, 2.77 +/- 0.32%; binding by HA-BP, 2.58 +/- 0.35% mean +/- SEM). A 4-fold increase to maximal binding for LA-BP occurred by the age of 5 yr and remained relatively constant through adolescence, except for a transient decrease at puberty. From 16.5-20 yr of age, binding by LA-BP decreased to a level no greater than that seen at birth. Binding by the HA-BP, which increased 6- to 8-fold reached maximal binding between 23-25 yr of age. Binding by HA-BP did not decrease in adults between the ages of 20-30 yr. Whereas pregnancy increased LA-BP activity, GH binding by HA-BP was unaltered. PMID- 1517378 TI - A circadian rhythm of serum follicle-stimulating hormone in women. AB - While a nocturnal decline in serum LH levels in the early follicular phase of the menstrual cycle has been well established, a diurnal variation in serum FSH levels in women has not been demonstrated. We addressed this issue by determining serum LH and FSH levels at 15-min intervals for 24 h in the early follicular phase (EFP; n = 16) and late follicular phase (LFP; n = 10) of the menstrual cycle and in postmenopausal women (PMW; n = 10). Serum estradiol was simultaneously measured at hourly intervals. As expected, EFP, but not LFP and PMW, women had a 15% nocturnal decline (P less than 0.01) in transverse mean LH levels compared to values in the daytime hours. In contrast, nocturnal FSH transverse mean values were significantly lower than daytime values in all groups studied, demonstrating an 18% decline in EFP (P less than 0.001), a 17% decline in LFP (P less than 0.00001), and a 4.3% decline in PMW (P less than 0.01). Cosinor analysis revealed a circadian rhythm for FSH, with acrophases in the afternoon and nadirs at night in all three groups. The circadian amplitudes were 1.43 +/- 0.22, 1.02 +/- 0.16, and 8.42 +/- 1.31 IU/L for EFP, LFP, and PMW, respectively. The EFP nocturnal decline in LH did not conform to a cosine rhythm. A diurnal variation in estradiol was not present in any of the groups of women. These data constitute the first demonstration of a robust circadian rhythm of serum FSH in women. The comparable timing of the acrophase in all groups of subjects and its presence in the postmenopausal years suggest a central, rather than peripheral, feedback mechanism(s) for the circadian rhythmicity. This observation provides strong evidence for a dissociation in the hypothalamic regulation of pituitary LH and FSH secretion in women. The circadian peak and nadir of circulating FSH may prove to be determining for appropriate follicular development. PMID- 1517379 TI - Combined effects of RU486 and tamoxifen on the growth and cell cycle phases of the MCF-7 cell line. AB - The antiproliferative effect of RU486 and its effect combined with tamoxifen on the growth and cell cycle kinetics parameters on the MCF-7 human carcinoma cells were investigated. When MCF-7 cells in the exponential growth phase were treated with RU486 (10(2) nmol/L), a time-dependent cell growth inhibition was observed which was significant 5 days after the beginning of treatment. This inhibition was accompanied by a time- and dose-dependent decrease in the percentage of S and G2-M phase cells and a concomitant increase in the percentage of cells in the G0/G1 phase of the cell cycle. With tamoxifen (10(5) pmol/L), growth inhibition was obtained after 4 days of treatment of cells, and the blockage of the cell cycle occurred in the G0/G1 phase. In the case of simultaneous treatment of MCF-7 cultures with RU486 (10(2) nmol/L) and tamoxifen (10(5) pmol/L), we observed a synergistic inhibitory effect on the proliferative rate for short treatment (less than or equal to 3 days), whereas RU486 or tamoxifen alone had no effect. For the intermediate treatment (4 days), the combined effect of RU486 and tamoxifen was not significant compared to the effect of tamoxifen alone. For the long treatment (greater than 4 days), there were no differences between the number of cells in the treated cultures under different experimental conditions, but all were inhibited compared to those in control cell cultures. This simultaneous treatment of cells does not induce any change in the distribution of cells in the different cell cycle phases compared to tamoxifen percentages. These results suggest that RU486 is a cell cycle phase-specific growth inhibitory agent, and a combination of antiestrogen/antiprogestin should be considered as a possible improvement in breast cancer endocrine therapy. PMID- 1517380 TI - A prospective trial of phosphate and 1,25-dihydroxyvitamin D3 therapy in symptomatic adults with X-linked hypophosphatemic rickets. AB - Current treatment of X-linked hypophosphatemia (XLH) employs the combined administration of oral phosphate and 1,25-dihydroxyvitamin D3 [1,25-(OH)2D3]. Although this drug regimen significantly improves the clinical course of the disease in children, the value of medical treatment in symptomatic adults with XLH has not been established. We, therefore, investigated the clinical, biochemical, and histological responses to phosphate and 1,25-(OH)2D3 in 16 symptomatic adult patients with XLH followed for a mean of 4.2 yr. Eighty-seven percent of the patients had an improvement in bone or joint pain with therapy. There was a significant increase in mean serum phosphate (from 0.61 +/- 0.03 to 0.77 +/- 0.03 mmol/L) and urinary calcium excretion (from 2.45 +/- 0.38 to 4.39 +/- 0.44 mmol/day) with treatment. Pretreatment bone biopsies demonstrated findings characteristic of osteomalacia, including abnormally increased osteoid volume and decreased mineral apposition rates. Treatment was accompanied by a significant decrease in osteoid thickness as well as a reduction in mean osteoid volume. However, therapy did not completely normalize these parameters. Disease severity, as assessed by histomorphometric parameters, did not correlate with any pretreatment serum or urinary biochemical measurement, but did seem to correlate with symptom score. Although most patients tolerated therapy without difficulty, 1 patient developed tertiary hyperparathyroidism during treatment and renal insufficiency that progressed despite cessation of therapy. This study provides evidence that therapy with oral phosphate and 1,25-(OH)2D3 in symptomatic adults with XLH can result in significant clinical and histomorphometric improvement. PMID- 1517381 TI - Does Graves' disease or thyrotoxicosis affect the prognosis of thyroid cancer. AB - Twenty-one patients who underwent surgical treatment for thyrotoxicosis and who were found at operation to have thyroid cancer are presented. Sixteen had Graves' disease and 5 had toxic nodular goiter. The group with Graves' is compared with 110 euthyroid patients with thyroid cancer who underwent their initial surgery in the same time period and who were of the same age (+/- 1 yr) and sex as the patients with Graves' disease. None of the thyrotoxic patients died during follow up of 2-24 yr or developed subsequent metastases. The 1 patient with a local lymph node metastasis has not shown evidence of recurrence. Hypoparathyroidism appeared as a complication in only 1 patient. The size of tumors in the patients with Graves' disease was significantly smaller than in the euthyroid group. The course of the disease in both the patients with Graves' disease and the thyrotoxic group as a whole was relatively benign. This series does not support the recent suggestions that thyroid cancer in patients with Graves' disease is more aggressive than in either patients with toxic nodular goiter or euthyroid subjects. Patients with Graves' disease and thyroid cancer should be treated identically to other patients with thyroid cancer. Therapy should consist of total thyroidectomy followed by a postoperative 131I scan. Residual tissue or metastases found on the scan should be ablated with 6 GBq 131I. The patient should receive a suppressive dose of T4. PMID- 1517382 TI - Ovulation and menstrual function of adolescent girls with central precocious puberty after therapy with gonadotropin-releasing hormone agonists. AB - Chronic GmRH agonist (GnRHa) administration has been shown to suppress pituitary gonadal function in children with central precocious puberty (CPP), but long term data after the reactivation of gonadarche posttherapy are not yet available. This study evaluated the menstrual function of 46 girls with CPP who had been treated for at least 2 yr with GnRHa (deslorelin or histrelin, sc, daily) and were up to 7 yr posttreatment, including 21 postmenarcheal girls who collected weekly overnight urine samples for 12 consecutive weeks to assess rates of ovulation by urinary pregnanediol-3 beta-glucuronide measurements. Menarche occurred at age 12.1 +/- 1.0 yr (mean +/- SD), on the average 1.2 +/- 0.8 yr posttherapy (range, 0.1-4.3 yr). Menstrual cycle lengths became increasingly regular, with cycles of 25- to 35-day duration reported by 41% of the girls in the first year postmenarche and 65% of the girls studied 3 or more years postmenarche. Ovulation was demonstrated in 50% of the girls studied within 1 yr of menarche and in 90% of the girls studied 2 yr or more postmenarche, including 5 girls who reported pregnancies. The development of regular ovulatory menstrual function in these girls with CPP is in accord with previously documented patterns in normal adolescents. While these data provide further evidence supporting the safety of long term GnRHa therapy, continued studies will be necessary to characterize fully the reproductive function in CPP patients through adolescence and adulthood. PMID- 1517384 TI - Highest concentrations of prorenin and human chorionic gonadotropin in gestational sacs during early human pregnancy. AB - Prorenin is not only the biosynthetic precursor of renin; under certain circumstances in vitro prorenin exhibits reversible intrinsic renin activity and can form angiotensin from renin substrate with or without cleavage of the prosequence. Prorenin is the predominant form of renin synthesized by reproductive organs (ovary, chorion laeve of the placenta, uterine decidua). Its plasma concentrations increases 10-fold throughout pregnancy to 10-100 times that of renin; amniotic fluid prorenin concentration is even higher. No data are available of gestational fluid prorenin concentrations during early pregnancy. For the first 10 weeks there are two gestational cavities; the chorionic cavity then disappears and the smaller amniotic cavity becomes predominant. In this study we measured prorenin, renin, renin substrate and hCG in fluid aspirated from gestational sacs during the first trimester of gestation (predominantly chorionic) and during the second and third trimesters (amniotic). Seventeen patients had amniocentesis during the second or third trimester. Nine patients underwent selective abortion of multiple pregnancy at 7-12 weeks gestation. One patient underwent surgery at 5 5/7 weeks (26 days after conception) for a tubal pregnancy. Second and third trimester amniotic fluid prorenin maximum velocity (Vmax) (16 and 3 sacs, respectively) averaged 6,100 +/- 1,700 (SD) and 1,930 +/- 760 ng/mL.h, respectively (i.e. 1,700 and 540 ng/L.s). In gestational fluid collected before 8 weeks, prorenin Vmax was 10-fold higher, averaging 62,500 +/- 40,000 ng/mL.h (17,000 ng/L.s). The concentration was 140,000 ng/mL.h (39,000 ng/L.s) in the 5 5/7 week tubal pregnancy. In sharp contrast, at 10-12 weeks gestation (n = 3) prorenin Vmax was only 260 +/- 114 ng/mL.h (72 ng/L.s); human CG was also highest before 8 weeks (276,500 +/- 110,900 IU/L) and lowest at 10-12 weeks (1210 +/- 540 IU/L) with intermediate levels occurring later in pregnancy. This study shows that the highest biological levels of prorenin yet detected (close to 1 micrograms protein/mL) occur in gestational sacs in early pregnancy, consistent with a role for the renin-angiotensin system in embryonic development or placentation. PMID- 1517383 TI - Organ-specific effects of tiratricol: a thyroid hormone analog with hepatic, not pituitary, superagonist effects. AB - Tiratricol has been used to suppress pituitary TSH secretion, with reported attenuation of extrapituitary thyromimetic effects. A randomized, double-blind trial was performed to define precisely the tissue-specific thyromimetic actions of tiratricol. Ten athyreotic patients, treated for thyroid carcinoma, were randomly assigned to receive L-T4 sodium 0.7 micrograms/kg daily and either tiratricol 10 micrograms/kg or placebo twice daily. The daily dose of L-T4 was increased by 25-50 micrograms increments until the TRH-stimulated TSH level was less than 0.1 mU/L. After measurement of biochemical and physiological parameters of thyroid hormone actions, patients crossed treatment groups. Patients required 46% less L-T4 to achieve equivalent TSH suppression when taking tiratricol. Hepatic effects were enhanced by tiratricol administration, with significant increases in sex hormone binding globulin and ferritin concentrations, 14% and 37%, respectively. Levels of serum cholesterol, LDL cholesterol, and apolipoprotein B were reduced by 7%, 10%, and 13%, respectively, during tiratricol therapy. Triglyceride levels also declined, but there were no changes of high density lipoprotein cholesterol or apolipoproteins AI and AII. Resting metabolic rate, body weight, urea nitrogen excretion, and symptoms did not differ between the two treatment regimens. Cardiovascular function, as reflected by mean arterial pressure and pulse wave arrival time, was not different during tiratricol therapy. Skeletal metabolic activity was affected by tiratricol, with marked elevation of osteocalcin without significant change in serum calcium, PTH, and urinary calcium and hydroxyproline excretion. Tiratricol has increased hepatic and skeletal actions of potential therapeutic value, but does not have enhanced thyromimetic activity specific to the pituitary gland. PMID- 1517385 TI - The inhibitory effects of mullerian-inhibiting substance on epidermal growth factor induced proliferation and progesterone production of human granulosa luteal cells. AB - This study was undertaken to determine if Mullerian-inhibiting substance (MIS) could block basal and/or epidermal growth factor (EGF)-induced proliferation and progesterone production by cultured human granulosa-luteal cells. Cells from follicles of individual patients were pooled, counted, and aliquoted into Ham's F 10 medium containing 10% MIS-free female fetal calf serum at 37 C in 95% air and 5% CO2. After assessing viability, cells were counted on days 4, 8, 12, and 16 of culture. EGF was added every other day at 0.2, 2, and 20 ng/mL beginning on culture day 4. The greatest stimulatory effect of EGF on cell proliferation was observed at 20 ng/mL on days 12 and 16. EGF increased progesterone production per cell after 4 days exposure, but this effect was lost after 8 days. Granulosa luteal cells were cultured with 0.2, 2, and 20 ng/mL immunoaffinity purified recombinant human MIS (rhMIS) or conditioned medium from Chinese hamster ovary cells transfected with the human MIS gene, beginning on culture day 4. rhMIS demonstrated its greatest inhibitory effect on cell proliferation at 20 ng/mL on day 16. The rhMIS decreased progesterone production per cell after 4 days exposure, but only in the higher doses. Maintaining EGF at 20 ng/mL and varying rhMIS yielded significant reduction in EGF-mediated proliferation and progesterone production per cell at 2 and 20 ng/mL rhMIS. These experiments demonstrate rhMIS inhibits basal and EGF-stimulated human granulosa-luteal cell proliferation and progesterone production. PMID- 1517386 TI - Glycoprotein hormone alpha-subunit production in somatotroph adenomas with and without Gs alpha mutations. AB - Activating mutations of the Gs alpha subunit have been identified in a subset of somatotroph adenomas. The mutant form of the Gs alpha subunit causes persistent activation of adenylyl cyclase and consequently results in high intracellular levels of cAMP. Because cAMP is known to stimulate the synthesis of the glycoprotein hormone (GPH) alpha-subunit as well as GH, we examined somatotroph tumors with and without Gs alpha mutations for GPH alpha-subunit production. GPH alpha-subunit production was assessed in vivo by measuring serum hormone levels and in vitro by analyzing hormone secretion by cultured pituitary tumor cells. DNA was extracted from the pituitary tumors of 26 acromegalic patients. The Gs alpha gene was amplified by the polymerase chain reaction and screened for mutations at codons 201 and 227 using oligonucleotide specific hybridization. Nine of the 26 tumors (35%) had point mutations at Arg 201. Seven of these tumors contained a CGT to TGT mutation (Arg to Cys) and 2 contained a CGT to CAT mutation (Arg to His). No mutations were detected at codon 227. There were no significant differences in age, sex distribution, tumor size, or serum levels of GH or insulin-like growth factor-1 between the groups of patients with or was Gs alpha mutations. The mean serum level of the free GPH alpha-subunit was 1.9-fold higher in the group with Gs alpha mutations (0.48 +/- 0.37 micrograms/L) than in patients without mutations (0.25 +/- 0.17) (P less than 0.05). In pituitary tumor cell culture, 75% of somatotroph tumors with Gs alpha mutations secreted free GPH alpha-subunit into the media compared with 45% of tumors without Gs alpha mutations. The amount of GPH alpha-subunit secretion was 12-fold greater in the group of tumors containing the Gs alpha mutation (P less than 0.05). Immunocytochemical detection of the free GPH alpha-subunit was similar in the two groups of patients with 75% positive for the GPH alpha-subunit in tumors with Gs alpha mutations and 67% positive in tumors without mutations (P = 0.69). We conclude that GPH alpha-subunit production occurs in somatotroph tumors with and without Gs alpha mutations. The increased levels of GPH alpha-subunit secretion in vivo and in vitro suggest that the Gs alpha mutation may increase the amount of preexisting GPH alpha-subunit biosynthesis in the tumors, perhaps via activation of the cAMP pathway. PMID- 1517387 TI - Plasma neurotransmitter profile during different phases of the ovulatory cycle. AB - The influence of the different phases of the menstrual cycle on platelet-poor plasma norepinephrine (NE) and serotonin (5HT) was examined in 17 normal volunteers. The examinations were performed consecutively during 3 phases of the ovulatory cycle: 1) follicular phase, 2) ovulation, and 3) luteal phase. This investigation was initiated after a preliminary study in 51 volunteers showed wide and consistent variations of plasma NE and 5HT during the different phases of the cycle. Since in this first group the determinations had not been performed consecutively in the same subjects, and the changes observed in the different phases of the cycle could reflect interpersonal variations, the determinations were performed consecutively in a second group, concomitantly with serum estradiol (E2) and LH measurements. The results showed a decrease in plasma 5HT from the follicular phase [144.3 +/- 69.3 nmol/L (+/- SD)] to ovulation (55.7 +/- 41.4; P less than 0.001) and a subsequent increase in the luteal phase (141.3 +/- 96.4; P less than 0.01). The nadir in plasma 5HT showed an inverse correlation with serum LH (r = -0.07). Plasma NE increased from the follicular phase (1226.5 +/- 475.1 pmol/L) to ovulation (1694.0 +/- 564.4; P = 0.027) and reached a maximum in the luteal phase (2335.0 +/- 728.2; P = 0.0034). This rise correlated positively with serum E2. In conclusion, plasma 5HT and NE vary with the different phases of the menstrual cycle. Plasma NE rises during ovulation and seems to to correlate positively with serum E2 levels. Plasma 5HT reaches a nadir during ovulation and correlates inversely with serum LH. PMID- 1517388 TI - Alterations in spontaneous growth hormone (GH) secretion and the response to GH releasing hormone in children with nonorganic nutritional dwarfing. AB - The effects of suboptimal nutrition on the spontaneous overnight GH secretion (SGHS) and the GH response to GHRH were studied. Sixteen patients with nonorganic nutritional dwarfing (ND) were compared with 25 healthy short children with familial short stature with or without constitutional growth delay (FC). The effects of puberty were also assessed. All patients underwent an overnight study to assess SGHS with serum GH levels sampled every 20 min for 12 h, and a GHRH stimulation test was administered. Pubertal ND children had a blunted SGHS with a mean overnight GH level of 4.9 +/- 1.1 micrograms/L, significantly less than the level of 6.2 +/- 1.8 micrograms/L of the pubertal FC children (P less than 0.05). Also, prepubertal ND patients had an area under the curve in GH secretion after GHRH which was greater than that of the pubertal ND patients (2483 +/- 1581 vs. 1600 +/- 1056, P less than 0.05). The peak GH response to GHRH in the prepubertal ND patients was also higher than that of the pubertal ND patients (51.8 +/- 22.1 micrograms/L vs. 22.5 +/- 15.4 micrograms/L, P less than 0.05). This study shows that the SGHS is attenuated in ND patients during puberty but their GH response to GHRH is increased before adolescence. These abnormalities may represent compensatory mechanisms to energy restriction and may increase our understanding of the poor growth seen in ND patients. PMID- 1517389 TI - Long term follow-up of Cushing's disease treated with reserpine and pituitary irradiation. AB - Twenty adult patients with Cushing's disease treated with long term reserpine administration in combination with a single course of external pituitary irradiation were followed. Eleven patients experienced long term remissions of 15.5 +/- 8.9 (mean +/- SD) yr (55%) after a mean irradiation dose of 53.9 +/- 11.4 Gy and a mean duration of reserpine administration of 24.3 +/- 9.3 months. The long term remission rates of the patients irradiated with 50 Gy or less (n = 9; 45.0 +/- 7.1 Gy) and those with more than 50 Gy (n = 10; 61.3 +/- 3.3 Gy; excluding 1 irradiated with 66 Gy who developed brain necrosis) were 56% (5 of 9) and 60% (6 of 10), respectively, and did not differ significantly. There were no significant differences between the 2 groups with regard to the duration of reserpine administration or pretreatment clinical features. At the latest examination, regardless of the irradiation dose, all 9 patients with long term remission showed a higher level of plasma cortisol or 11-hydroxycorticosteroids in the morning than in the evening, normal suppressibility of plasma cortisol with overnight 1 mg dexamethasone (9 of 10), and well preserved responses of other pituitary hormones to various loading tests: normal responses of plasma ACTH to CRH (6 of 9), TSH (7 of 8), and PRL (5 of 8) to TRH and age-related normal responses of GH to GRH (4 of 8), LH (6 of 8), and FSH (6 of 8) to GnRH. These findings suggest that long term reserpine administration in combination with a conventional dose of pituitary irradiation is useful in the treatment of Cushing's disease. PMID- 1517390 TI - Typing for major histocompatibility complex class II antigens in thyroid tissue blocks: association of Hashimoto's thyroiditis with HLA-DQA0301 and DQB0201 alleles. AB - This study was undertaken 1) to find out whether we can type major histocompatibility class II antigens from the paraffin-embedded series of thyroid tissue, and 2) to investigate whether HLA-DQ genes are involved in conferring a risk of Hashimoto's thyroiditis. To this end we used the polymerase chain reaction to amplify DNA from paraffin-embedded thyroid tissue blocks of histologically proven Hashimoto's disease. We used 46 specimens for HLA-DQA and 32 for DQB typing. The alleles were identified by sequence-specific oligonucleotide hybridizations. Fifty controls from the same geographic region were also typed using peripheral leukocyte DNA. HLA-DQA0301 (in linkage disequilibrium with DR4) was significantly increased (58.7% vs. 32% in controls; chi 2 = 6.73; P less than 0.01) in patients compared to controls. DQB0201 (in linkage disequilibrium with DR3) was also increased in the patient group (66% vs. 36% in controls; chi 2 = 6.63; P less than 0.01). Although DQA0301/DQB0201 heterozygotes (18.8%) were increased in patients compared to controls (6%), the difference was not significant. However, 81% of the patients (26 of 32) were DQA0301 and/or DQB0201 positive compared to 48% of controls (chi 2 5.98; P less than 0.05). We conclude that it is feasible to type HLA antigens from tissue blocks and that susceptibility to Hashimoto's disease is probably mediated through two pathways: DQA0301/DR4 and DQB0201/DR3. PMID- 1517391 TI - Interleukin-1 is induced in the human placenta by endotoxin and isolation procedures for trophoblasts. AB - Although freshly obtained placenta contains little or no interleukin-1 (IL-1) mRNA, placenta and isolated trophoblast have been reported to produce significant quantities of bioactive IL-1 in vitro. The present study was designed to determine if endotoxin, a common contaminant of culture medium, and trophoblast isolation procedures could induce IL-1 expression in the placenta. Tissue extractable IL-1 alpha and IL-1 beta immunoreactive proteins were readily detected in fresh placental membranes, but not placental villi. As little as 10 ng/mL endotoxin were found to induce the expression of IL-1 alpha and IL-1 beta mRNA in intact placental villi cultured in vitro. Intact placenta cultured in the presence of 1.0 microgram/mL endotoxin demonstrated expression of IL-1 alpha and IL-1 beta mRNA and cumulative production and release of immunoreactive IL-1 alpha and IL-1 beta into the medium during 24 h of culture. Placenta incubated in endotoxin-free medium, however, exhibited no detectable IL-1 alpha or IL-1 beta mRNA expression and little or no release of IL-1 alpha or IL-1 beta immunoreactive protein into the medium. When trophoblast cells were freshly isolated by enzymatic digestion, followed by Percoll separation at reduced temperatures to inhibit cell activation, no IL-1 alpha or IL-1 beta mRNA expression was initially detectable. However, IL-1 alpha and IL-1 beta mRNA in isolated trophoblast cells were induced after 30 min of culture in endotoxin-free medium, with maximal induction at 4 h. These results suggest that normally the placenta produces very little, if any, IL-1, and that endotoxin and trophoblast isolation procedures induce IL-1 expression in placental tissues cultured in vitro. PMID- 1517392 TI - Distribution of F-actin during mouse facial morphogenesis and its perturbation with cytochalasin D using whole embryo culture. AB - Histological and experimental studies were performed in mouse embryos to elucidate possible roles of actin filaments in the nasal epithelium during facial morphogenesis. C57BL/6 mouse embryos (8.5-11.5 days of gestation) were fixed and frozen sections were stained with rhodamine-phalloidin. Before formation of the nasal placode, there was no specific localization of F-actin. After the nasal placode was formed, intense staining of F-actin was observed at the apical side of the placode. Conversely, it was located at the basal side of the epithelium of developing nasal prominences. By using the whole embryo culture system, perturbation experiments were conducted with cytochalasin D (CD), which inhibits the polymerization of actin filaments. When day-10 embryos were exposed to CD at several concentrations for 24 hr, fusion of nasal prominences was inhibited in a dose-dependent manner. Treatment with a high dose of CD for 2 hr also prevented the same development irreversibly. In contrast, when day-9 embryos were exposed to CD at several concentrations for 24 hr, invagination of the nasal placode was not perturbed at all. The results suggest that apical F-actin plays an essential role in maintaining the close apposition state of the nasal prominences and in the following fusion. During the invagination stage, F-actin might be important in maintaining the epithelial structure, but is not crucial to the initiation of placode invagination. PMID- 1517393 TI - A morphometric analysis of craniofacial growth in cleft lip and noncleft mice. AB - Differences in face shape are considered a factor in cleft lip malformation. The purpose of this study was to analyze craniofacial growth in two strains: A/WySn with 28% cleft lip and C57BL/6J without cleft lip. Standardized photographs of 27 A/WySn and 25 C57BL/6J embryos with 34-46 somites (S) were taken in the superior, frontal, and lateral views. Landmarks were located and digitized for computerized analysis of growth change relative to somite number and at stages of face development before, during, and after primary palate closure. The results showed that both strains had similar overall growth patterns with increases in head width and face width, and decreases in nasal pit width. During early palatal closure in C57BL/6J mice, the nasal pit width was unchanged as brain width increased rapidly; and then later, the nasal pit width decreased as brain width increased slowly. However, during early closure in A/WySn mice, the nasal pit width decreased rapidly as brain width increased slowly; and then later, the nasal pit width was unchanged as brain width increased more rapidly. During early palatal closure, the narrower nasal pit width in A/WySn mice appeared to result from delayed growth of the supporting forebrain as the nasal pits become more medially positioned with normal face development. From the lateral view, the maxillary prominence depth was also smaller in the A/WySn strain during early palatal closure. This deficient forward growth of the maxillary prominences and the narrower positioning of the medial nasal prominences in A/WySn embryos appear to reduce the contact between the prominences and thus predispose this strain to cleft lip malformation. PMID- 1517394 TI - Palate teratogenicity and embryotoxicity of cyclosporin A in mice. AB - Mice of the A/J and B10.A/SgSnJ strains were treated with 50 mg of cyclosporin A (CsA) per kg of body weight on day 12 of gestation. There were significantly more fetal resorptions in both the A/J and B10.A strain when treated with CsA than in controls treated with olive oil. A low frequency (7.6%) of isolated cleft palates were induced in the A/J strain, which was significantly greater than that observed in A/J mice treated with olive oil alone. No cleft palates were induced in B10.A, which suggests that any increase in susceptibility that was observed could not be attributed to H-2 linked genes. PMID- 1517395 TI - Scoring mitotic activity in longitudinal sections of mouse embryonic incisors: significant differences exist for labial and lingual inner dental epithelia. AB - The incisors of rodents (e.g., mice and rats) have an enamel-free lingual surface. It is not known how position specific differential evolution of labial versus lingual inner dental epithelium (IDE) is regulated. The patterns of mitotic activity of lingual and labial preodontoblasts and IDE were determined on sagittal sections of embryonic mouse incisors. No statistical differences were observed for the preodontoblasts. On the other hand the lingual IDE withdraw from the cell cycle before the corresponding labial cells. The incapacity of lingual IDE to differentiate into functional ameloblasts might be a consequence of a failure of cell kinetic dependent acquisition of competence to respond to specific epigenetic control mechanisms. PMID- 1517396 TI - Cavitation defects on the lingual ramus: a further expression of Stafne's defect. AB - Seven archaeological examples of 6,700 mandibles examined were found to have developmental cortical defects on the ramus. The defects, unusual in their position, were grossly and radiographically similar to developmental bone cavities (Stafne's) located in the sublingual region. Of the seven ramus defects, all of which were in adult males, six were in Alaskan Eskimos from Kodiak Island (N = 5) and Nelson Island (N = 1), and one was in a native American from Arkansas. Only five adult males from Finland have been reported with similar defects. A statistical examination of the metrics defining mandibular cavitation defects, along with prevalence data, suggest that the seemingly rare findings of ramus defects are an extreme manifestation of the continuum of severity of the Stafne's defect. Bilateral Stafne's defects also represent a severe manifestation. PMID- 1517397 TI - A craniometric study of bicoronal craniosynostosis (BCC). AB - We compared 20 cases of bicoronal craniosyntosis (BCC) using the linear and angular values of the normal statistical material for the same age and sex. The skull in BCC is significantly shortened and flattened but with normal width. The height of the frontal arch (FNBR) is significantly decreased. The base of the skull is depressed with angle AB2 significantly increased, and angle NTNO significantly decreased and, even in some cases, with negative angular values. This is inducing a sinking of LEA (length from N to T), and in some cases LEA is lower than the line LNO (distance from N to O). The cephalic index (CI) was significantly increased, and the calculated cranial capacity (CC) was significantly decreased. Bregma (BR) is moving anteriorly in BCC, inducing an anterior movement of the calvaria with a bulge around BR. In this anterior movement we designate lack of positive occipital rotation. In BCC there is an evident lack of positive occipital rotation. Superimposing our drawings on the reference line NBA, we found for the first time a movement of anatomical landmarks similar to that observed in the negative occipital rotation in vestibular orientation. PMID- 1517398 TI - Interleukin-1 beta induces corticotropin-releasing factor-41 release from cultured hypothalamic cells through protein kinase C and cAMP-dependent protein kinase pathways. AB - Interleukin-1 beta (IL-1 beta) induces a dose-dependent increase in the release of corticotropin-releasing factor-41 (CRF) from dispersed rat fetal hypothalamic cells in culture. This release of CRF could be inhibited by the protein kinase C inhibitor H-7, and by the protein kinase A inhibitor IP-20. This suggests that both protein kinase C and protein kinase A-dependent pathways are involved in the response of CRF to IL-1 beta. Dexamethasone also blocked the CRF response to IL-1 beta, indicating that activated glucocorticoid receptors can inhibit the response of CRF to IL-1 beta. PMID- 1517399 TI - Ovalbumin is more immunogenic when introduced into brain or cerebrospinal fluid than into extracerebral sites. AB - The magnitudes of serum antibody responses to ovalbumin have been compared following immunization via cerebral or extracerebral sites in Sprague-Dawley rats. In central nervous system (CNS)-immunized rats, conditions were designed to ensure normal brain barrier permeability. Extracerebral immunization was via the footpad or along pathways of antigen outflow from the CNS. The relative immunogenicity of different injection sites is: CSF greater than brain tissue greater than extracerebral sites. Enhancement of the antibody response to CNS administered antigen appears to depend on events initiated within the CNS, since ovalbumin injected into blood (which reaches the spleen) or nasal submucosa (which drains to cervical nodes) fails to elicit a similar response. PMID- 1517400 TI - Evidence for activation of the complement cascade in the hypoglossal nucleus following peripheral nerve injury. AB - Following hypoglossal nerve transection in adult rats, immunoreactivity for complement factor C3 and one of its degradation products C3d as well as C4d and immunoglobulin G (IgG) was observed in the ipsilateral hypoglossal nucleus. Double-labelling experiments indicated that these antigens were present in perineuronally located reactive microglial cells. In addition, increased levels of complement factor C3-mRNA was found in perineuronally located cells ipsilateral to nerve lesion. These results suggest that the complement cascade is locally activated in the vicinity of axotomized neuronal perikarya and that microglial cells have a key role in this process, alternatively that C3, C3d, C4d and IgG are involved in other so far unknown processes. PMID- 1517401 TI - Evoked potentials in infants and children. PMID- 1517402 TI - Somatosensory evoked potential testing in infants and children. AB - Somatosensory evoked potentials (SSEPs) provide the means to assess noninvasively the peripheral and central nervous system in infants and young children. As experienced clinicians know, this is the very system most difficult to adequately evaluate in young children. Physical examination is difficult. SSEPs provide information about function of somatosensory systems not otherwise available. In addition to pathologic states, maturation and sleep produce changes in SSEPs that require careful analysis. PMID- 1517403 TI - Intraoperative electrophysiological monitoring in children. AB - Children, like adults, are at risk for neurological injury during a variety of surgical procedures. Intraoperative electrophysiological monitoring (IOM) provides information about the functional integrity of the nervous system during surgery. This information may determine the mechanism of injury and prevent damage by identifying nerves and detecting dysfunction at a reversible stage. Electrophysiological techniques may also help direct therapy by improving injury localization, detect the presence or absence of axonal integrity in peripheral nerve lesions, and identify rootlets with the greatest contribution to spasticity in patients undergoing selective dorsal rhizotomy (SDR). Electrophysiological techniques used are modified from those employed in the diagnostic laboratory. The first portion of this article reviews IOM experience at the Mayo Clinic in patients under 18 years of age from 1985 to 1991. The types of procedures monitored, the monitoring modalities used, technical problems unique to children, and neurological outcome are discussed. Subsequently presented are the application and techniques of electrophysiological monitoring during SDR as currently practiced at the University of Kentucky and other medical centers. PMID- 1517404 TI - Visual evoked potentials in infants and children. AB - Visual evoked potential (VEP) studies are of great value in a wide variety of pediatric patients, including those with disorders of the sensory visual pathway and those at risk for visual pathway damage. VEPs are simple, non-invasive, and are particularly appropriate for infants and young children who cannot communicate visual symptoms or cooperate for standard vision assessment. VEPs in pediatric patients have the following main purposes: (1) detecting lesions causing dysfunction of the sensory visual pathways (the VEP is a sensitive indicator of subclinical lesions and can be used to differentiate visual impairment from visual inattention in young infants); (2) confirming functional loss when disorders of the visual system are present; (3) quantifying visual impairment in patients with known visual disorders, accomplished either empirically by noting the severity of the VEP abnormality to flash and pattern stimuli or by visual acuity estimation studies (early quantification of vision loss allows referral to early intervention programs, which can ameliorate the long-term consequences of the disability); (4) monitoring patients who are at risk for visual complications either from diseases (such as hydrocephalus or neurofibromatosis) or as a complication of therapeutic intervention (e.g., neurosurgery, chemotherapy) to help detect and avoid long-term sequelae of such therapies on the developing nervous system; (5) establishing prognosis for visual and systemic recovery based on flash VEPs for specific pediatric disorders including perinatal asphyxia in full-term neonates, acute-onset cortical blindness, and, to a fair extent, in comatose children; and (6) in some cases, contributing to the differential diagnosis. Abnormalities of flash and/or pattern VEPs are generally nonspecific to the type of exact location of the lesion, except in distinguishing prefrom postchiasmal lesions. However, in certain conditions, such as the hereditary ataxias of childhood, VEP abnormalities may help in the diagnosis. Similarly, deterioration in VEPs may help differentiate progressive from static encephalopathies. VEPs have become an indispensable tool in pediatric ophthalmology and neurology. They will probably play an increasingly important role in the future, primarily due to the difficulty in assessing visual system function in young or ill children and the VEP's sensitivity to subclinical damage in this aspect of the central nervous system. PMID- 1517405 TI - The electroretinogram in infants and young children. AB - Electroretinography (ERG), especially when combined with visual evoked potential recording, can provide valuable information to the pediatric clinician assessing a young child with nystagmus who appears not to see. ERG changes are described in clinical conditions affecting rod and/or cone function, vitreoretinal disease, maculopathies, and disorders involving the retina and central nervous system. The role of ERG in monitoring treatment, and in excluding retinal disease prior to eye surgery, is also covered. PMID- 1517406 TI - The brainstem auditory evoked potential in infants and children. AB - The brainstem auditory evoked potential (BAEP) is a neurophysiological study that provides functional information about the auditory system and brainstem. It provides information that is different from any other form of evaluation. This report tries to summarize technical and clinical information that will make the BAEP more meaningful for the practicing technologist and clinician. Attention is focused on the BAEP as it is used in infants and children, starting with a brief review of auditory physiology, then progressing to normative data, clinical utility, physical setup, preparing the patient, comments on technique, and comments on interpretation. This is not an exhaustive review of the topic, and many important elements of clinical utility had to be left out. This review tries to focus on recent references and on practical issues, and it relies on the experience and opinions of the author. Emphasis has been placed on the use of the BAEP by the neurologist, but an attempt has been made to acknowledge the importance of audiology and otolaryngology as well as speech and language science. Particular emphasis has been placed on the use of the BAEP in assessing the premature infant and young infant at risk for neurological and audiological injury. An enormous amount of published data is available in the literature, and much of it had to be left out of this review. However, the reader is encouraged to develop an enthusiasm for the BAEP and to further explore the broad range of its clinical uses. PMID- 1517407 TI - Event-related potential studies in infants and children. AB - The current status of event-related potentials (ERPs) in infants and children is discussed based on a review of the relevant literature. Although the N100-P200 component evoked by tone stimuli is clearly detected using an odd-ball paradigm in children over approximately 6 years of age, that component evoked by speech stimuli is not clearly detected until at least 10 years of age. In contrast to the adult N100-P200 component evoked by speech stimuli, infants and young children show a positivity at a latency of about 85-120 ms and a negativity at about 200-240 ms. The definition of P300 in children has not yet been established. P300 latency evoked by both auditory and visual stimuli decreases throughout childhood and reaches the mature value by puberty or young adulthood. However, P300s elicited by auditory and visual stimuli show different developmental time courses from each other, suggesting that they may originate from different neural generators. The Nc component is elicited by a variety of attention-getting events in infants and children. Interestingly, the developmental change in the Nc amplitude parallels the maturational course of synaptogenesis in the frontal cortex, and the Nc latency reaches the mature value at the time when myelinogenesis is complete in the nonspecific thalamic radiation. PMID- 1517408 TI - In memoriam Albert Melvin Grass. 1910-1992. PMID- 1517409 TI - The American Electroencephalographic Society: the original cast of characters. PMID- 1517410 TI - Relationship of age to power spectrum analysis of EEG during sleep. AB - We describe a method of power spectrum analysis of all-night sleep EEGs in 20 normal subjects aged 18-43 years. The analysis calculates the energy of the whole sleep period, the various frequency bands, and selected sleep stages automatically. The numerical value of the energies was directly comparable between subjects, presented in numbers (microV2s) and displayed as a color density spectral array with fixed power values for each color. A significant relationship between age and power spectra was found, in that total energy/minute was higher in younger subjects than in older. The energy in delta sleep/minute also showed an inverse relationship with age. PMID- 1517411 TI - Effects of age, gender, and stimulus side on the scalp topography of somatosensory evoked potentials following posterior tibial nerve stimulation. AB - This is the first thorough study to evaluate the effects of age, gender, and stimulus side on the scalp topographies of somatosensory evoked potentials (SEPs) following stimulation of the posterior tibial nerve by using computerized bit mapped color images and the significance probability mapping method. Seventy-four normal subjects whose ages ranged from 7 to 88 years were studied. Topographic mappings of most components in aged subjects were significantly different from those in young subjects, mainly because of higher amplitudes of the components in the aged group. However, scalp distribution of each component did not show a large difference among different age groups. There was a tendency that amplitudes in women were larger than those in men, and the gender differences of some components were significantly larger for some age groups. Stimulus side and handedness caused no significant difference in amplitudes and topographies of the components. These results were very similar to our previous results of the scalp topographies of SEPs following median nerve stimulation. PMID- 1517412 TI - High-frequency EEG activity at the start of seizures. AB - Frequencies above 35-40 Hz are poorly visualized on conventional EEG scalp recordings. We investigated frequency components up to 150 Hz in digitally recorded EEGs of seizures in five patients with implanted subdural grids, as part of their evaluation for epilepsy surgery. Amplifier bandpass was set from 0.1 to 300 Hz, and EEG was digitized at 2,000 samples per second. Seizures with electrodecremental patterns at the start showed a significant increase in spectral power above 35 Hz, with a twofold increase in the 40-50-Hz range, and up to a fivefold increase in the 80-120-Hz portion of the spectrum. Activity above 40 Hz could represent summed action potentials, harmonics of synaptic potentials or transient sharp components of synaptic potentials. High-frequency increases were largely localized to the region of the seizure focus. Grid sites remote from the focus did not show significant energy in the EEG band above 40 Hz at baseline, nor at time of seizure onset. Our findings suggest that high-frequency recordings may be of use in localizing seizure foci. PMID- 1517413 TI - Lateral shelf acetabuloplasty: an operation for older children with Perthes' disease. AB - Although 59% of children with Perthes' disease have a good result without treatment, poor results are common when the disease has onset in older children. Femoral osteotomy at this age will control the disease but may leave shortening and a persisting limp if there is insufficient capacity for remodeling and growth. Twenty children aged greater than 8 years with early disease were treated by lateral shelf acetabuloplasty. The results are compared with those in 14 children for whom no treatment had been advised. Lateral shelf acetabuloplasty has improved early outcome for these children as compared with untreated children for whom a poor prognosis has been confirmed. PMID- 1517414 TI - Slotted acetabular augmentation in childhood and adolescence. AB - During an 18-year period, 157 hips in 140 patients with hip dysplasia underwent a slotted acetabular augmentation (SAA or shelf) procedure. Indication for the procedure was pain in 71, progressive subluxation in 52, and acetabular insufficiency in 34 hips. Follow-up of 24-168 months (mean 60 months) was obtained in 108 hips in 98 patients. Good or excellent results were recorded in 83% of the hips. Unsatisfactory results were usually due to excessive breadth or insufficient thickness of the augmentation. The SAA is an alternative to the Chiari osteotomy when lateralization of the hip is not excessive. PMID- 1517415 TI - Computed tomographic assessment of shelf acetabuloplasty. AB - Eleven children with cerebral palsy were studied after shelf acetabular augmentation for progressive hip subluxation. Evaluation was based on computed tomography (CT) scans and radiographic measurements. We noted significant improvement in subluxation as measured by migration percentage, without increased subluxation of the nonoperated hip. Preoperatively, our patients had anterior acetabular deficiencies and increased acetabular anteversion, but no posterior deficiency by CT scanning. The acetabular shelves were positioned relatively more anteriorly than posteriorly. This appears to be appropriate owing to the relative anterior deficiencies of the acetabuli in our patients. PMID- 1517416 TI - The value of the acetabular teardrop figure in assessing pediatric hip disorders. AB - We have observed that the acetabular teardrop figure provides extremely useful information about the development of the hip in young children. Normal development of the acetabulum is associated with progressive narrowing of the teardrop figure and development of a concave shape to its acetabular line. Anatomic and functional abnormalities of the hip can cause abnormalities of the teardrop figure, including absence of the acetabular line, persistent widening, and a V-shaped teardrop figure. In young children, these abnormalities can be reversed to some degree by stabilizing operations, but it is unusual to observe substantial change in appearance of the teardrop figure after a child is aged 8 years. PMID- 1517417 TI - Arthroscopy for slipped capital femoral epiphysis. AB - Arthroscopy was performed in five hips with slipped capital femoral epiphysis (SCFE) before pinning in situ. Arthroscopy disclosed erosion of acetabular cartilage in the anterosuperior region and damage to the posterolateral aspect of the acetabular labrum. Cartilaginous erosion and transverse cleft were identified on the anterior surface of the femoral head. These findings support the hypothesis that all pathomechanisms of SCFE are caused by traumatic factors. Arthroscopy for SCFE is also clinically useful in reducing hip pain. Arthroscopy performed simultaneously with pinning in situ can permit early exercise of the joint. PMID- 1517418 TI - Congenital dislocation of the hip and its relation to swaddling used in Turkey. AB - A screening program was initiated and performed at five hospitals in Konya, Turkey from 1988 to 1990. Four thousand one hundred seventy-three infants aged 3 24 months were examined. With this study, we hoped to determine the incidence of and contributing factors to the etiology of congenital dislocation of the hip (CDH) in the central region of Turkey. The overall CDH incidence was 1.34%. CDH occurred about three times more often among girls than boys (40 girls vs. 16 boys). No infant with CDH had been delivered by Cesarean section or breech presentation. No teratologic CDH was detected. The relationship between CDH and swaddling (bundled in extension and adduction) was statistically significant. PMID- 1517419 TI - Ludloff's open reduction of the hip: long-term results. AB - Long-term results of Ludloff's open reduction of the hip were studied in 62 joints of 56 children with an average follow-up of 11 years (range 5-18 years). Results were considered good in 76% and poor in 24%. A decisive factor in assessing long-term results was a proper centric reduction of the femoral head. The most frequent obstacles to proper reduction were a shortened inferomedial part of a joint capsule with the transverse ligament pulled into the joint cavity (14%), joint capsule contracture (100%), and an inverted limbus (92%), which was accompanied in 17% of patients by an impression of reflected head of the rectus femoris. Earlier nonoperative treatment affected the success of the reduction as well as long-term results. PMID- 1517420 TI - Perthes' disease and posterior lumbosacral union. AB - Delayed bone development is common in Perthes' disease, and affected children are usually smaller than normal. Somatosensory evoked potentials (SEP) studied in 25 cases of Perthes' disease were normal. Fifty-four patients with active or healed Perthes' disease were examined. Every child aged less than 8 years showed failure of posterior lumbar and/or sacral fusion. With growth, fusion increased so that at age 14 years 50% had a normal fusion and 50% had spina bifida occulta. At age greater than 16 years, the incidence was similar to that in the general population. In Perthes' disease, growth in fusion of the lumbosacral elements is delayed. PMID- 1517421 TI - Comparison of one-stage versus two-stage anterior/posterior spinal fusion for neuromuscular scoliosis. AB - Twenty-six patients with progressive neuromuscular scoliosis underwent anterior/posterior (AP) spinal fusion. Thirteen of the patients underwent a one stage fusion, and 13 underwent a two-stage fusion. Although one-stage AP spinal fusion provides adequate correction of severe curves and allows a more expeditious recovery without increasing patient morbidity or mortality, current third-party payor reimbursement policies provide little incentive for 1-day operations. In addition, the procedure is mentally and physically demanding and the apparent benefits must be weighed against the potential harm that can result from surgeon fatigue or lack of appropriate planning. PMID- 1517422 TI - Spinal cord concussion in pediatric athletes. AB - Children with a narrowed canal secondary to spinal stenosis or congenital malformation may be predisposed to spinal cord concussion when the canal is further narrowed in hyperflexion or hyperextension. Review of the medical records of the Winnipeg and Ottawa Children's Hospitals disclosed 12 children who had been treated for transient sensory or motor loss after a spinal injury. Measurements of the spinal canal were compared with standard normal measurements, and the spinal canal width was expressed as a percentage of the vertebral width (the Torg ratio). This study shows that narrowing of the spinal canal is an inconsistent predisposing factor to spinal cord concussion in children. A poor correlation between the Torg ratio and comparison with a series of normal control canal widths was noted. PMID- 1517423 TI - Acetabular and pelvic fractures in the pediatric patient: value of two- and three dimensional imaging. AB - Pediatric trauma is a significant source of morbidity and mortality in pediatric patients. Prompt and accurate assessment of injuries is necessary for the best outcome. Computed tomography (CT) has become a well-accepted, rapid, relatively noninvasive way to assess the trauma patient. In certain cases of pelvic trauma, two- and three-dimensional CT (2D/3D CT) adds detail not otherwise obtainable or appreciated. Although the benefits must be balanced against the slight increase in delivered radiation dose, we believe that 2D/3D CT is often an important part of patient management. PMID- 1517424 TI - Compression plating for child and adolescent femur fractures. AB - Twenty-five children ranging in age from 6-16 years underwent AO compression plate fixation for treatment of a femur fracture. Generally, the most common reason for plate fixation was to simplify nursing care and rehabilitation of children with an associated severe head injury or polytrauma. Twenty-three fractures healed in 11 weeks on the average, most by periosteal bone formation. Leg length discrepancy was not a clinical problem. Nursing care and polytrauma rehabilitation were simplified in all children. We believe that plate fixation is a reasonable treatment option for femoral fracture care in children aged less than 11 years with severe head injury or associated polytrauma. PMID- 1517425 TI - Low-dose lidocaine intravenous regional anesthesia for forearm fractures in children. AB - Intravenous (i.v.) regional anesthesia with low-dose lidocaine (1 mg/kg) lidocaine 1% diluted to 0.125% vol) provided safe and effective anesthesia for closed reductions of pediatric forearm fractures in outpatients. This procedure was prospectively evaluated in 44 children at The Nemours Children's Clinic, Jacksonville, Florida. Forty-three of 44 patients achieved adequate anesthesia (minimal or no pain on closed reduction). No significant complications were noted. Both patients and physicians were satisfied with the procedure. Patient pain was objectively assessed with visual pain charts in the preanesthesic, immediate postanesthetic, and postreduction time periods. The technique was both safe and effective in providing pain relief for reduction of forearm fractures in children. PMID- 1517426 TI - Normal characteristics of the Baumann (humerocapitellar) angle: an aid in assessment of supracondylar fractures. AB - We evaluated the normal Baumann (humerocapitellar) angle in 114 children aged 2 13 years because the angle has been proposed to be useful in assessing alignment of the elbow in children with supracondylar fractures of the humerus. In this age range, the angle did not change significantly, nor was there any significant difference between the angle in boys and girls. The mean Baumann angle was 72 degrees (SD 4 degrees), and 95% of normal elbows had a Baumann angle of 64 degrees-81 degrees. PMID- 1517427 TI - Shoulder arthrodesis in pediatric patients. AB - Shoulder arthrodesis was performed in 17 pediatric patients. Diagnoses included birth-related brachial plexus palsy (six patients), posttraumatic palsy (three patients), and residual paralysis after poliomyelitis (eight patients). The position of fusion was not as important as the stability gained by the patient. Excessive abduction or forward flexion should be avoided, however, because this can be cosmetically displeasing to patients. PMID- 1517428 TI - Totally absorbable screws in fixation of subtalar extra articular arthrodesis in children with spastic neuromuscular disease: preliminary report of a randomized prospective study of fourteen arthrodeses fixed with absorbable or metallic screws. AB - Seven patients with spastic neuromuscular disease and severe hindfoot valgus deformity were treated by subtalar arthrodesis. Arthrodesis was performed in both feet at the same operation and fixed on one side with a self-reinforced poly-L lactide (SR-PLLA) screw, and with a standard AO screw on the other side. The functional status state was improved, and radiographic union of the arthrodesis occurred in all feet. The radiograph showed better solid fusion in five feet treated with PLLA screws, similar fusion in both sides in one patient, and one slower fusion in the side treated initially with a PLLA screw. Totally absorbable SR-PLLA screws appear to be firm enough for fixation of subtalar extraarticular arthrodesis in children. PMID- 1517429 TI - Management of congenital fibular deficiency by Ilizarov technique. AB - Between April 1987 and January 1990, 11 patients with congenital fibular deficiency underwent tibial lengthening of 12 involved limbs by the Ilizarov technique. The average follow-up was 23.2 months. The mean lengthening was 8.3 cm, representing an average lengthening of 31%. No knee or ankle subluxation occurred despite preoperative cruciate ligament laxity and ankle abnormalities in all patients. The most significant complications included regenerate bone deformation and delayed consolidation. With the Ilizarov technique, the limb length discrepancy, angular and rotational deformities, and foot and ankle deformities frequently associated with congenital fibular deficiency can be addressed simultaneously. PMID- 1517430 TI - Toxic shock syndrome in patients with external fixators. AB - Toxic shock syndrome (TSS), first described by Todd et al. in 1978, can be a life threatening entity. Familiarity with the pathogenesis and clinical presentation of TSS may help achieve early diagnosis and prompt appropriate intervention. TSS is not a septicemia, but a toxemia. The most extensively described pathogenesis involves a focus of specific Staphylococcus aureus strains capable of producing an exotoxin (TSST-1). We report two patients who developed TSS while in external fixators and describe their initial symptoms, management, and subsequent problems. This report will serve to alert pediatric orthopaedic surgeons to this entity and enable them to recognize its rather precipitous presentation and initiate appropriate treatment. PMID- 1517431 TI - Acute pyogenic psoas abscess in children. AB - In a retrospective study, 24 patients treated at King Edward VIII Hospital from 1985 to 1988 for acute pyogenic psoas abscess were reviewed. The main initial complaints were a painful hip and difficulty in walking. Twenty-two patients had a fixed flexion deformity of the ipsilateral hip. Ultrasonography used as a screening method elucidated the clinical diagnosis in 19 patients. Twenty-two children required incision and drainage, and Staphylococcus aureus was isolated in 20 patients either on blood culture or pus swab. Although the condition is common in the tropics, an acute pyogenic psoas abscess should always be considered in the differential diagnosis of pain in the hip region. PMID- 1517432 TI - Musculoskeletal manifestations of Proteus syndrome: report of two cases with literature review. AB - Proteus syndrome is a recently described hamartomatous condition characterized by macrodactyly, hemihypertrophy, subcutaneous (s.c.) tumors, epidermal nevi, and skull anomalies. Two new cases are described to illustrate the diagnostic features and the orthopedic problems associated with this rare syndrome. Review of available literature shows that 61 patients with proteus syndrome commonly develop macrodactyly, limb overgrowth, spinal deformity, hip dysplasia, genu valgum, exostoses, joint contractures, and hindfoot deformities. PMID- 1517433 TI - Congenital absence of the lumbar spine and sacrum: one-stage reconstruction with subsequent two-stage spine lengthening. PMID- 1517434 TI - Intravenous regional anesthesia: a safe and cost-effective outpatient anesthetic for upper extremity fracture treatment in children. PMID- 1517435 TI - Lumbosacral joint angles in children. PMID- 1517437 TI - Object relations deficits in subtypes of schizophrenia. AB - Forty-eight subjects with diagnoses of schizophrenia were assessed with the Bell Object Relations Inventory (BORI), the Positive and Negative Syndrome Scale (PANSS), the Brief Psychiatric Rating Scale (BPRS), and the Premorbid Adjustment Scale (PAS) to determine the distribution of object relations deficits in the whole sample and four subtypes: paranoid, schizoaffective, poor premorbid, and prominent negative symptoms. Results indicate that 92% of the sample had object relations deficits; 85% showed elevations on the BORI Alienation scale. Subjects with prominent negative symptoms produced lower values on Insecure Attachment and higher values on Egocentricity. This suggests that negative symptoms are associated with a reduction in perceived painfulness of attachment and increased egocentric investment. Other subtyping schemes showed no reliable pattern of object relations deficits. PMID- 1517436 TI - Self-concept dimensions of clinically depressed and anxious outpatients. AB - Principal components analyses of the Beck Self-Concept Test (BST) were conducted independently for 288 women with primary mood disorders, 230 women with anxiety disorders, 236 men with mood disorders, and 161 men with anxiety disorders. Four self-concept dimensions that reflected (1) Intellectual Ability; (2) Work Efficacy; (3) Physical Attractiveness; and (4) Virtues/Vices occurred within the four samples. For 5-item subscales that represent these four dimensions, a two way MANOVA found significant effects for sex and type of disorder. Women described themselves as having less intellectual ability than men did. Outpatients with mood disorders considered their physical appearance, work efficacy, and virtues/vices to be less acceptable than did those with anxiety disorders. Findings were discussed with respect to the cognitive content specificity theory of psychopathology. PMID- 1517438 TI - Family functioning and child abuse potential. AB - Family conflict and the lack of family cohesion are believed to set a foundation for coercive interactions that increase the likelihood of child abuse. The present study investigated the relationship between the family social environment (Family Environment Scale and Index of Marital Satisfaction) and physical child abuse potential (Child Abuse Potential Inventory) in maltreating (n = 376) and comparison (n = 148) parents. As expected, the strongest positive relationship was between family conflict and abuse potential. The strongest inverse relationships were between family cohesion, family expressiveness, marital satisfaction, and abuse scores, which indicates that the lack of positive interactional patterns is related to abuse potential. However, regression analysis revealed that family interactional patterns did not account for the majority of variance in abuse potential. PMID- 1517439 TI - Assessing the severity of depressive illness. AB - Twenty-five psychiatrists ranked a set of hypothetical patient scenarios, based on the three depression rating scales (Hamilton, Hospital Anxiety and Depression, and Montgomery Asberg), in terms of severity of illness. The results indicate some scope for comparing different condition-specific outcome measures. Although the patient scenarios were context free, the responses of the psychiatrists suggested that they might be used to assess severity of depressive illness. PMID- 1517441 TI - Bulimia and fear of intimacy. AB - Many authors have suggested that fear of intimate relationships is a central dynamic in bulimia. However, empirical studies have yielded conflicting results. Eleven women who met the DSM-III-R criteria for bulimia and 23 women who denied binging and/or engaging in purging behavior completed the Fear of Intimacy Scale (Descutner & Thelen, 1991). This instrument is the first instrument to measure fear of intimacy reliably and has been found to be valid for this purpose. As predicted, bulimic subjects evidenced significantly greater fear of intimacy than did control subjects. PMID- 1517440 TI - The influence of weight reduction and exercise regimes upon the personality profiles of overweight males. AB - In the present study, the MMPI was used to detect personality changes in 53 overweight, yet otherwise healthy, males who were participating in either a weight reduction or an aerobic exercise conditioning program. Analysis of pre- and post-intervention scores revealed that only the participants in the aerobic conditioning group demonstrated the predicted desirable psychological changes. More specifically, this group displayed significant clinically desirable changes on the Hs, PD, and HEA scores. Similar to the weight loss participants, a demographically matched nonintervention comparison group showed none of these desirable changes and actually yielded a significant increase on the D scale. However, when compared to this "normal" group, both intervention programs showed statistically significant differences on at least two MMPI scales. PMID- 1517442 TI - Age, stage, and the MMPI: changes in response patterns over an 85-year age span. AB - Statistically significant and clinically relevant age-related changes in MMPI response patterns have long been known to clinicians. Graphic representations of mean scores that cover an 85-year age span, separately by sex, for each of the 13 basic MMPI validity and clinical scales support the use of adolescent norms and indicate that clinicians should give greater acknowledgement to age-related MMPI changes in adults and their interpretation, particularly among geriatric patients. PMID- 1517443 TI - Ego-strength revised: a comparison of the MMPI-2 and MMPI-1 versions of the Barron Ego-strength scale. AB - This study evaluated the equivalence of the original MMPI and the shortened MMPI 2 versions of the Barron (1953) Ego-strength scale, an important research scale. Three hundred fifty-five subjects took the MMPI-2 and the 16 MMPI-1 items dropped from the original scale. The omitted items appear to contribute little to the original scale. The revised version compares favorably with the old in terms of internal consistency, and the two versions are highly intercorrelated. Confirmatory Factor Analysis indicates that four of Stein and Chu's (1967) five groupings of the original items provide a reasonably good fit for the MMPI-2 as well. Compared to the original, the new version was slightly more correlated with other paper-and-pencil measures of psychological health and well-being. PMID- 1517444 TI - The Bulimic Automatic Thoughts Test: initial reliability and validity data. AB - The Bulimic Automatic Thoughts Test (BATT) was designed to address some of the limitations found in previous measures of the cognitions of bulimic patients. In this study, bulimic, depressed, obese, and normal subjects were differentiated on the BATT, which suggests that it is a useful measure for detecting cognitions specific to bulimic patients. Scores on the BATT improved after a trial of cognitive-behavioral therapy for the bulimic subjects. The BATT may be useful in predicting which bulimic women will continue to have distorted thinking after treatment and will require additional intervention. PMID- 1517445 TI - Suicide and time perspective: an examination of Beck and Yufit's suicide-risk indicators. AB - Both Beck and Yufit have developed indices of risk for suicidal groups. An investigation with 86 university students explored the concurrent and convergent validity of both scales. The current study reports moderate correlations between these two measures as a test of concurrent validity. In addition, both authors argue for the importance of time perspective in the development of these tests. The Hopelessness Scale was found to correlate well with other attitudinal measures of time perspective. The correlational pattern of the Time Questionnaire presented a less coherent pattern of association across temporal orientation, extension, and temporal attitude scales. PMID- 1517446 TI - The revised Generalized Expectancy for Success Scale: a validity and reliability study. AB - The Generalized Expectancy for Success Scale (GESS; Fibel & Hale, 1978) was revised and assessed for reliability and validity. The revised version was administered to 199 college students along with other conceptually related measures, including the Rosenberg Self-Esteem Scale, the Life Orientation Test, and Rotter's Internal-External Locus of Control Scale. One subsample of students also completed the Eysenck Personality Inventory, while another subsample performed a criterion-related task that involved risk taking. Item analysis yielded 25 items with correlations of .45 or higher with the total score. Results indicated high internal consistency and test-retest reliability. PMID- 1517447 TI - Conventional intelligence measurements and neuropsychological concepts of adaptive abilities. AB - The concept of intelligence and its representation by the Intelligence Quotient have been difficult to define and the subject of criticism for various reasons. Matarazzo and Kaufman have reviewed intelligence measurements and brain functions, but a biologically based explication of intelligence has not been explicitly proposed since the theories presented more than 40 years ago by Halstead and Hebb. The present study explored the overlap and differential sensitivity of intelligence measures (VIQ, PIQ, and FSIQ) and neuropsychological measures (Impairment Index and Category Test) to cerebral damage and educational attainment. The results indicated that neuropsychological measures may serve to broaden the concept of intelligence and that a brain-related criterion may contribute to a fuller understanding of its nature. PMID- 1517448 TI - Memory and attention. AB - The effect of attention on memory was examined in three studies. In all three, the subjects were instructed to remember the items of one color from an array that contained items of two colors. Subsequently, the subjects were asked to reproduce items of both colors. Almost all of the items that the subjects remembered were those to which they had attended. The parameters of sex, color, and mode of presentation (verbal and drawing) were not significant. Head injury did not disrupt this effect. On the basis of this effect, it was theorized that the strength of a memory store is related directly to the strength of attention. PMID- 1517449 TI - Psychotherapist personality characteristics and the perception of self and patients in the treatment of borderline personality disorder. AB - The influence of certain personality characteristics (tendency to depressive experiences, personal boundary preferences) on psychotherapist reaction to patients with borderline personality disorder was assessed by semantic differential ratings in an analogue study. Vignettes presented one of two patients enacting the Rewarding and Withdrawing object relations unit in two separate therapy sessions. Therapists higher on anaclitic depressive and fusion tendencies evaluated themselves less positively than other therapists (p less than .01) in the Withdrawing condition. They evaluated the patient less positively regardless of condition (p less than .05). High boundary therapists evaluated patients more positively (p less than .05) in the Withdrawing condition. They evaluated themselves more positively regardless of condition (p less than .05) and showed less tendency to devalue self and patient with the lower functioning borderline patient. PMID- 1517450 TI - Psychotherapist perceptions of self and patients in the treatment of borderline personality disorder. AB - Psychotherapists' reactions to patients with borderline personality disorder were assessed by semantic differential ratings in an analogue study. Vignettes presented one of two patients who enacted the Rewarding and Withdrawing object relations units in two separate therapy sessions. In response to the Rewarding object relations unit therapists evaluated themselves more positively and perceived themselves as more active and more potent than in response to the Withdrawing object relations unit (p less than .01). They also evaluated the patients more positively and perceived them as less active (p less than .01). These patterns were modified by some order effects and some differences in response to the two vignettes, which represented a lower and higher functioning borderline patient. PMID- 1517451 TI - Appropriateness of the Draw-A-Person test with Alaskan Native populations. AB - The appropriateness of the Draw-A-Person test with Alaskan Native populations was assessed by matching 33 White subjects to 33 Alaskan Native subjects, asking them to perform the DAP, and rating their performance according to eight criteria chosen for their clinical relevancy. Results indicated that neither level of commitment to Native culture nor ethnicity per se affected drawing ratings. It is hypothesized that the DAP is a useful clinical tool appropriate for use with Alaskan Native populations. PMID- 1517452 TI - An archival study of decision-making in child custody disputes. AB - Investigation files and court records of 282 disputed child-custody cases (San Diego, 1982) were coded and analyzed to determine predictors of judicial decision. Log-linear analysis of physical custody decisions as a function of factors contained in the files suggested that three categories of factors (mother, father, and child) were linked causally to a counselor's recommendation, which was linked subsequently to the judge's decision. Judicial decisions could be predicted accurately by a model that took very few factors into account. Only two factors directly affected the judge; counselor-recommendation and child preference. The major factor that influenced decisions was counselor recommendation (60% of the cases); cases that lacked this recommendation were predicted by an inferential measure of the child's preference (15% of the cases). PMID- 1517453 TI - Bone marrow transplantation for thalassaemia major. PMID- 1517454 TI - Chromosome studies of solid tumours. PMID- 1517455 TI - Circulating secretory component in relation to early diagnosis and treatment of liver metastasis from colorectal carcinomas. AB - AIMS: To evaluate serum secretory component in relation to early detection and clinical management of liver metastasis in patients with colorectal cancer. METHODS: Secretory component and carcinoembryonic antigen (CEA) were analysed in serial serum samples from 23 patients who had liver metastases as the only apparent recurrence, and in sera from 54 matched controls. Results of surgical treatment of recurrences were classified peroperatively as radical when no residual tumour was apparent and resection margins were free of disease. RESULTS: In total, 18 (78%) patients had increased secretory component during the whole follow up period (median 16 months); 12 (52%) had raised secretory component concentrations before clinical recurrence (median lead time 5.2 months). There was no difference before recurrence between circulating secretory component and CEA in sensitivity and lead times. Seventeen patients underwent surgery for hepatic metastasis; seven had radical hepatic resection of which only two (29%) showed increased secretory component concentrations before clinical recurrence; both had concurrent raised CEA values. By contrast, secretory component was raised in 83% of those cases considered inoperable. CONCLUSIONS: Although serum secretory component clearly increases in most patients with liver metastases, its clinical value seems questionable because secretory component apparently indicates mainly inoperable hepatic metastases. PMID- 1517456 TI - Computerised protocols for laboratory investigation and their effect on use of medical time and resources. AB - AIMS: To devise a computerised management system protocol which not only proposes the laboratory investigations to be performed on each patient but also performs related clinical functions. METHODS: The system was designed by senior members of staff. The protocols defined all laboratory investigations including haematology, biochemistry, immunology and cross-matching, and included static and dynamic rules. Patients can be changed to different or additional protocols, as required; likewise proposed tests can be deleted or added. The software is written in MUMPS and runs on a 386 PC running MSM MUMPS under MSDOS. RESULTS: The number of clinical chemistry tests requested per patient per day fell by 9.5% (p less than 0.01) for transplant recipients and by 28.8% (p less than 0.01) for non transplant recipients. The average time spent by junior medical staff requesting laboratory investigations and enquiring about results fell from 10 minutes per patient per day to 4.1 minutes (p less than 0.001). CONCLUSIONS: The introduction of this system in no way abrogates clinicians' responsibility for the management of patients, because all proposed investigations must be confirmed or modified by the authorising doctor. The system allows for the audit of requesting patterns and subsequent improvement in protocols by recording any alterations made to the proposed investigations. Significant benefits in terms of better use of house officer time and medical resources were also achieved. PMID- 1517457 TI - Prospective study of necropsy audit of geriatric inpatient deaths. AB - AIMS: To evaluate the accuracy of clinical diagnosis by specialists in geriatric medicine and to compare this with a previous study involving non-specialists. METHOD: Clinical and necropsy diagnoses from consecutive hospital inpatient deaths from the University Department of Geriatric Medicine were analysed for discrepancies at regular audit meetings. Three main categories of diagnosis were considered and any therapeutic implications discussed. RESULTS: Between 1987 and 1989 necropsies were performed on 100 patients (38 men, 62 women, aged 63 to 99 years) from a total of 207 deaths, a necropsy rate of 50%. There was complete agreement between necropsy and clinical diagnoses in 32% of cases. Disagreement involved the main diagnosis in 28%, contributory conditions in 32%, and cause of death in 34%. In 10% of cases the diagnostic discrepancy was considered therapeutically important. Specialist geriatricians correctly diagnosed the main diagnosis in 72% of cases; non-specialists in the previous study were correct in only 47% of cases. CONCLUSION: Specialist geriatricians diagnose elderly people more accurately than non-specialists. But rates of misdiagnosis are still significant and necropsies continue to be a useful form of audit. PMID- 1517458 TI - Vascular invasion in non-small cell lung carcinoma. AB - AIMS: To determine if there is any correlation between vascular invasion and prognosis in non-small cell carcinoma of the lung; and to look specifically at invasion of vascular channels by tumour cells. METHODS: Eighty seven patients undergoing lobectomy or pneumonectomy for adenocarcinoma or squamous carcinoma were followed up for five years. The histological sections were studied for evidence of vascular invasion using an elastic van Gieson stain. The incidence of intimal fibrosis in arteries and veins was noted and the proportion with vascular invasion evaluated using a scoring system. The presence or absence of lymphatic permeation and tumour necrosis were noted. Survival data were analysed using the log rank test. RESULTS: The overall five year survival was 32%. There were 64 squamous cell carcinomas and 23 adenocarcinomas. Vascular invasion was seen in 77% of patients and lymphatic invasion in 44%. Neither the presence nor absence nor the proportion of blood vessels showing vascular invasion showed any relation to prognosis. Intimal fibrosis and tumour necrosis were unrelated to prognosis. Patients with lymphatic permeation had recurrence and died earlier than those without. CONCLUSION: The presence of arterial or venous invasion by adenocarcinoma or squamous carcinoma of the lung was unrelated to survival; lymphatic permeation was associated with poor prognosis. The two common non-small cell lung cancers behaved differently from other solid tumours, where vascular invasion was a significant factor in determination of prognosis. The presence of intimal fibrosis was unrelated to prognosis. PMID- 1517459 TI - Helicobacter pylori serology in patients with coeliac disease and dermatitis herpetiformis. AB - AIMS: To investigate whether Helicobacter pylori infection or autoimmune gastritis is responsible for the reported increase in gastric pathology and abnormalities of gastric function in patients with coeliac disease and dermatitis herpetiformis (DH). METHODS: Serum H pylori IgG antibodies were assayed by enzyme linked immunosorbent assay and intrinsic factor antibodies by radioimmunoassay in 99 patients with coeliac disease and 58 patients with dermatitis herpetiformis from two geographic areas. RESULTS: H pylori positivity in patients with coeliac disease and dermatitis herpetiformis increased with age, reaching 50% and 70%, respectively, in patients over 50 years. The percentage H pylori seropositivity in coeliac disease did not differ from the percentage positivity observed in 250 similarly aged blood donors from the same geographic area (Leeds). Seropositivity in patients with dermatitis herpetiformis was not significantly different from the level of positivity observed in 98 age matched patients without dermatitis herpetiformis attending the same Edinburgh dermatology clinic. Only one patient with coeliac disease had positive intrinsic factor antibodies. H pylori seropositivity in Edinburgh control subjects under 30 years of age (41.9%) was significantly higher (p less than 0.03) than in Leeds controls (18%) of corresponding age. An increasing prevalence of H pylori seropositivity with age in coeliac disease and dermatitis herpetiformis paralleled that of the control groups. CONCLUSIONS: Gastritis in coeliac disease and dermatitis herpetiformis is largely caused by H pylori infection at a level that is no different from that of the general population. Any increase in the prevalence of gastritis in these two diseases might be caused by lymphocytic gastritis rather than pernicious anaemia. PMID- 1517460 TI - Use of polymerase chain reaction for early identification of Mycobacterium tuberculosis in positive cultures. AB - AIMS: To develop a readily applicable polymerase chain reaction (PCR) based technique which would permit the identification of Mycobacterium tuberculosis complex isolates from Bactec phials at an earlier stage than currently available methods. METHODS: Mycobacterial cells cultured in Bactec 12B medium were harvested by centrifugation. The cells were lysed by heating in distilled water. Oligonucleotide primers based on the sequence of the gene coding for the immunogenic protein MPB64 were then used to amplify a 240 base pair fragment of DNA directly from the crude cell lysate. The PCR product was visualised under ultraviolet light following electrophoresis of an aliquot in an agarose gel containing ethidium bromide. The sensitivity of the PCR was adjusted so that about 600 cfu of M tuberculosis gave a positive result. The lowest growth index at which this method of identification might be applied to Bactec phials was determined and a number of routine cultures giving a positive growth index examined. RESULTS: M tuberculosis was positively identified at the lowest growth index, as determined by the Bactec system. Of 45 routine cultures examined, with growth indexes ranging from 6 to 999, the 15 confirmed by conventional means to contain M tuberculosis were correctly identified from 1 ml of culture medium. CONCLUSIONS: The method described can be used to identify M tuberculosis isolates cultured in the Bactec system at the earliest detectable rise in growth index. It may therefore allow cultured mycobacteria to be identified at an earlier stage than conventional methods or the commercially available DNA probes adapted for use with the Bactec system. PMID- 1517461 TI - IgA antibody response during acquired and congenital toxoplasmosis. AB - Toxoplasma gondii specific IgA and IgM antibodies were quantitated by an antibody capture agglutination assay in 260 patients with acquired toxoplasmosis and from 94 fetuses suspected of congenital toxoplasmosis and 30 infected children. In acquired toxoplasmosis, IgA antibodies to T gondii were found in 95% of the cases. In congenital toxoplasmosis IgA antibodies were more frequently detected (75%) in cord blood than IgM antibodies (61%). They persisted after birth, in some cases for up to 24 months. IgA antibodies were also detected in fetuses whose mothers had toxoplasmosis during their pregnancy. In infected fetuses IgM and IgA antibodies were detected in fetal blood as early as week 24 of pregnancy. Detection of IgA T gondii antibodies may be useful for the diagnosis of some recently acquired infection and for the diagnosis and follow up of the infection in the fetus and neonate. PMID- 1517462 TI - Detection of Clostridium perfringens and its enterotoxin in cases of sporadic diarrhoea. AB - AIMS: To determine the incidence of sporadic and apparently non-food related diarrhoea associated with Clostridium perfringens enterotoxin. METHODS: Enzyme linked immunosorbent assay (ELISA) and reversed phase latex agglutination (RPLA) were used to detect C perfringens enterotoxin in faecal specimens from 818 sporadic cases of diarrhoea. RESULTS: C perfringens enterotoxin was identified as a cause of sporadic diarrhoea in 56 of 818 (6.8%) cases. Diarrhoea was prolonged (three days or more) in most cases. Ages ranged from 3 months to 89 years, although most patients were over 60 years of age. CONCLUSIONS: These results suggest that C perfringens may be a cause of sporadic cases of diarrhoea when causes such as food consumption or cross-infection are absent, particularly in the elderly. PMID- 1517463 TI - Neuronal network analysis of serum electrophoresis. AB - AIMS: To advise a system of neuronal networks which can classify the densitometric patterns of serum electrophoresis. METHODS: Digitised data containing 83 normal and 132 pathological serum protein electrophoresis patterns were presented to four neuronal networks containing 1900 neurons. Network 1 evaluates the integrated values of the albumin, alpha 1, alpha 2, beta and gamma fractions together with total protein (Biuret method). Networks 2, 3, and 4 analyse the shape of the albumin, beta and gamma fractions. To increase the sensitivity for the detection of monoclonal gammopathies a Fourier transformation was applied to the beta and gamma fractions. RESULTS: After a learning period of 20 minutes (back-propagation learning algorithm) the system was tested with a set of electrophoresis patterns comprising 446 routinely collected samples. It differentiated between physiological and pathological curves with a sensitivity of 97.5% and a specificity of 98.8%, with 86% correct diagnoses. All monoclonal gammopathies were recognised by the Fourier detector. CONCLUSIONS: Neuronal networks could be useful for certain medical uses. Unlike rule based systems, neuronal networks do not have to be programmed but have the capacity to "learn" quickly. PMID- 1517464 TI - Transfusion associated graft versus host disease in an immunocompetent patient. AB - Transfusion associated graft versus host disease is a rare disorder usually confined to patients who are immunosuppressed. A case is described in a 77 year old woman who was presumed immunocompetent. She was transfused with one unit of blood from an individual who was homozygous for the same HLA haplotype as her. The diagnosis of transfusion associated graft versus host disease should be suspected in a patient who develops aplastic anaemia within 30 days of a transfusion of blood products. It is suggested that blood donations from first degree relatives should not be permitted, unless the donation is irradiated to prevent lymphocyte proliferation. PMID- 1517465 TI - Plasmacyte-reticulum cell satellitism in multiple myeloma associated with amyloidosis. AB - A novel morphological feature is described in a patient with myeloma and associated amyloidosis: characteristic clustering (satellitism) of neoplastic plasma cells around macrophages in bone marrow aspirates. Although described in myeloma cell culture, as far as is known, this is the first description of this phenomenon in a patient. This unique association may partly explain the origin of amyloid deposition in tissues and organs. PMID- 1517466 TI - Progressive multifocal leucoencephalopathy, sclerosing cholangitis, bronchiectasis and disseminated warts in a patient with primary combined immune deficiency. AB - A 24 year old man presented with an unusual primary combined immune deficiency syndrome characterised by a profound lymphopenia of CD4 cells, selective serum IgG2 subclass deficiency, poor polysaccharide antibody responses, disseminated warts, recurrent sinopulmonary infection and bronchiectasis. The developed progressive multifocal leucoencephalopathy (PML) in association with sclerosing cholangitis. Progressive multifocal leucoencephalopathy (PML) usually occurs as an opportunistic infection in patients with secondary defects in cellular immunity. PMID- 1517467 TI - Isolation of Legionella pneumophila serogroup 14 from a human source. AB - A strain of Legionella pneumophila serogroup 14 was isolated during a retrospective study, after death from the sputum of a patient who had had acute leukaemia and pneumonia. This is the third strain of that serogroup to be isolated from a human source. This event emphasises the importance of performing culture as well as serological tests, so as to detect cases of legionellosis caused by strains which rarely cause fatal clinical illness. PMID- 1517468 TI - Aspergilloma in the frontal sinus expanding into the orbit. AB - A case of primary frontal sinus aspergilloma in a 79 year old non immunocompromised woman, who presented with a right sided pyocele expanding into the orbit, is presented. The low susceptibility of the frontal sinus is probably related to the brachycephalic shape of the human skull which locates this sinus far anterosuperiorly to the nasal cavity. In human frontal sinus aspergillosis nasal symptoms are absent; the clinical manifestation of this rare disease is initiated by complications, especially orbital or intracranial invasion. Sinus opacity may raise early suspicion. Treatment consists of surgical debridement and re-aeration. Diagnosis is established by histological analysis of intraluminal contents. PMID- 1517470 TI - Draft quality assurance for surgeons in breast cancer screening. PMID- 1517469 TI - Effects of prolonged processing in standard and isotonic trichloroacetic acid (TCA) on cellular preservation in bone marrow trephines. AB - The effects of a combined fixing and decalcifying solution, trichloroacetic acid, on prepared bone marrow specimens were evaluated to try to improve the speed of trephine biopsy processing in our laboratory. The morphological preservation obtained immediately after decalcification was complete was assessed, and also after prolonged immersion in each of two solutions. Trichloracetic acid was made up in the standard manner using distilled water and in an isotonic form by the addition of sodium chloride. Prolonged immersion was performed to assess any possible adverse effects of this acidic solution. By the time decalcification was complete, each solution gave morphological preservation sufficient for diagnostic purposes. However, after prolonged immersion, only the isotonic solution performed adequately. PMID- 1517471 TI - External quality assessment. PMID- 1517472 TI - Depth-force patterns of periodontal probing. Attachment-gain in relation to probing force. AB - It was the purpose of this study to determine whether probing force had an influence on the amount of clinical attachment-gain assessed after treatment by scaling and rootplaning. A probing device was constructed which allowed simultaneous monitoring of probing force and probe penetration and which standardized the insertion pathway for repeated measurements. In 10 periodontal patients, 2 deep pockets were selected which were measured before and after periodontal treatment by scaling and root-planing. Depth-force plots were compared by superimposition. Depth values were determined at 5 different force levels (0.25, 0.50, 0.75, 1.00 and 1.25 N) on each plot and changes of clinical attachment levels were calculated. A significant relationship was seen between probing force and attachment level. The values obtained with 0.25 N were significantly different from the values obtained with higher forces (p less than 0.001). Slight, but non-significant differences were noted in the amount of attachment-gain obtained at the 5 force levels. At a probing force level of 0.25 N, there was 0.80 mm mean attachment gain. With 0.50 N, there was a gain of 0.70 mm; with 0.75 N the gain amounted to 0.67 mm in mean. At 1.00 N and at 1.25 N, a gain of 0.66 mm was recorded. PMID- 1517473 TI - Probe tine diameter and probing depth. AB - The aim of this study was to assess the effect of difference in tine diameter on probing pocket depth measurement. 2 sets of tines with Williams markings at 1, 2, 3, 5, 7, 8, 9 and 10 mm, and with a "round" tip, diameter 0.5 mm, were compared. One set was described as parallel-sided, the other as tapered. The parallel-sided tine was almost parallel from the 10 mm marking to the tip (tip diameter mean = 0.46 mm, 95% C.I. 0.456-0.464), while the corresponding diameter for the tapered tine varied (tip diameter mean = 0.48 mm, 95% C.I. 0.473-0.489). Calibration markings appeared highly consistent with the expected value to within 0.01 mm. The tines were mounted in Brodontic handles at 0.25 N. Examiner probing repeatability yielded kappa 0.86 for "parallel-sided" and 0.81 for "tapered" tines in vivo. 412 approximal pockets were assessed in 53 patients with routine chronic adult periodontitis, mean age 42.1 years. Each site had a probing depth of greater than or equal to 5 mm, PlI less than or equal to 1, GI less than or equal to 1, PBI less than or equal to 1. Each site was probed 2x with a 15-min interval. At the first 251 sites, the parallel-sided tine was used initially, and the tapered at the remaining 161 sites. Results indicated a highly significant tendency for the parallel-sided tine to yield a deeper reading when a difference occurred. These findings indicate that with adequate training providing high examiner repeatability, one source of error in probing data can be minimised. PMID- 1517474 TI - The incidence and severity of nifedipine-induced gingival overgrowth. AB - The gingival health of 19 patients with cardiovascular problems who were medicated with nifedipine was compared with a similar cohort treated with atenolol and a control group of healthy patients. In the nifedipine and atenolol groups, patients had been taking their respective medication for a minimum period of 6 months. Plaque scores were similar for all three groups. However, patients medicated with nifedipine had a significantly higher gingival index (P less than 0.005), gingival overgrowth scores (P less than 0.02) and probing sites greater than 3 mm (P less than 0.005) when compared with the atenolol and control groups. 4 patients in the nifedipine group experienced clinically significant gingival overgrowth which required surgical excision. Gingival changes in the nifedipine patients were not related to drug dosage or plaque scores. It is concluded that nifedipine therapy results in significant gingival changes, an effect which may be mediated by the drug's action on calcium transport. PMID- 1517475 TI - Maintenance of new attachment gained through guided tissue regeneration. AB - The aim of the present study was to evaluate whether new attachment, gained following guided tissue regeneration (GTR) therapy, can be maintained over longer periods of maintenance therapy. 88 sites at 52 teeth with various types of periodontal defects in 39 patients were treated with the GTR procedure during the period 1984-1989. The effect of treatment was evaluated by assessing probing attachment level (PAL) prior to surgery and 6 months post-surgery. Only sites which at the 6-month examination (baseline) had gained 2 mm or more of PAL were regarded as successfully treated and scheduled for further monitoring. At baseline, 80 sites could be identified which fulfilled this criterium. Of the 80 new attachment sites, all have been monitored for 1 year, 65 for 2 years, 40 for 3 years, 17 for 4 years and 9 sites for 5 years. The results demonstrated that the attachment gain, obtained as the result of the GTR treatment, could be maintained over periods up to 5 years. PMID- 1517476 TI - Elevated levels of the IgG2 subclass in serum from patients with a history of destructive periodontal disease. A case-control study. AB - The levels of the 4 subclasses of IgG were estimated in the serum from 35 patients with a history of chronic periodontitis and 35 matched controls. The levels of IgG2 were significantly (P less than 0.019) elevated in the patients (3.756 g l-1) compared to the controls (2.882 g l-1). The data suggest that the predominant antibody response to periodontal pathogens in periodontitis may be directed against carbohydrate or glycolipid antigens. PMID- 1517477 TI - Effect of 4 days of mouth rinsing with delmopinol or chlorhexidine on the vitality of plaque bacteria. AB - Delmopinol is a new surface active anti-plaque agent that has demonstrated a low antimicrobial effect in vitro. By use of a vitality staining technique, the antimicrobial effect on bacteria in plaque samples was tested after rinsing with delmopinol or chlorhexidine. 6 healthy male subjects volunteered to rinse for 4 days using a double-blind cross-over study design with a wash-out period between the rinsing regimens. No oral hygiene measures were allowed during the test periods and each test period started with a professional tooth cleaning procedure 2 days before the start of rinsing to allow for plaque formation. Rinsing was performed with 0.2% delmopinol hydrochloride or 0.2% chlorhexidine digluconate 2 x a day. Small samples of plaque were collected from the buccal surfaces of premolars and 1st molars before the first rinse on day 1 and then before and 1, 2, 4, 7, and 24 h after the last rinse on the 4th day. The plaque samples were immediately stained with propidium iodide and fluorescein diacetate to visualize dead and vital microorganisms respectively. The vitality of the microflora was evaluated using a fluorescence microscope. The baseline vitality values were 91% for chlorhexidine and 86% for delmopinol. At day 4, the plaque vitality for chlorhexidine was approximately 40% up to 4 h and 50% at 7 h and 60% at 24 h after the last rinse. Corresponding values for plaque vitality after delmopinol rinsing were between 70 and 80% on all sampling occasions.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1517478 TI - Comparison of panoramic and intraoral radiography and pocket probing for the measurement of the marginal bone level. AB - Panoramic, bitewing and periapical radiography and probing for measurement of the marginal bone level were compared. Altogether 237 sites of 23 patients were examined. Radiographs were taken with a splint containing steel balls to allow calculation of the enlargement of the radiographs. Probing was done before and during flap surgery using the same splint. The open bone measurement represented the true value. All radiographs were assessed by 5 observers. The mean enlargement of panoramic radiography was 27% in the upper and 26% in the lower arch. For bitewing and periapical radiography, it was 8% in the upper and 4-5% in the lower arch. All methods underestimated the bone loss. Probing bone level before surgery was most accurate, deviating at most 5% from the true value. Periapical radiography was more accurate than panoramic and bitewing radiography (p less than 0.001). Panoramic radiography presented a slightly lower mean accuracy than bitewing radiography (p less than 0.05). The underestimation of the bone loss ranged from 13 to 32% in orthopantomograms, 11-23% in bitewing and 9 20% in periapical radiographs. The interobserver variation of the radiographic methods was substantial. PMID- 1517479 TI - Comparison of a subgingivally placed cannula oral irrigator tip with a supragingivally placed standard irrigator tip. AB - This study compared the depth of irrigation of periodontal pockets achieved by a cannula subgingival irrigator tip and a standard oral irrigator tip. They were tested on periodontally involved teeth recommended for extraction from 17 patients. Before extraction, reference grooves were made circumferentially in each study tooth at the level of the gingival margin. In one group of 5 patients (29 teeth), a cannula was inserted halfway into the pocket at the facial, mesiofacial, distofacial, lingual, mesiolingual and distolingual surfaces and the surface irrigated for 5 s at 5 psi with a solution of plaque-staining dye from an oral irrigator. A 2nd group of 7 patients (29 teeth) was tested similarly with a standard irrigating tip at 80 psi. A 3rd (control) group of 5 patients (26 teeth) rinsed with the dye solution. Teeth were then extracted. The distance on each tooth from the reference notch to the apical extent of the stained plaque, and also to the coronal limit of the connective tissue attachment, was measured at 4 sites (mesial, distal, buccal, lingual) under a dissecting microscope to determine the extent of dye penetration. Mean linear penetration for the control group was only 0.1 mm. Irrigation with the cannula tip penetrated farther into both the medium (3.5-6 mm) and the deep (greater than 6 mm) periodontal pockets (p less than 0.01) than did irrigation with the standard tip.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1517481 TI - State of the art in oral implants. PMID- 1517480 TI - Healing of experimental wounds in sialadenectomized rat. AB - The present study evaluates the healing of an experimental standardized full thickness excisional wound in the palate of a sialadenectomized rat model. Experimental rats underwent sialadenectomy of the submandibular and sublingual glands and ligation of the parotid ducts. A full thickness circular wound, 3 mm in diameter, was produced in the palate. Wound diameter was measured clinically and the area of inflammation and area of new connective tissue formation were determined histologically at 3, 7, 14, 21 and 28 days post-surgery. Wound diameter was similar in both the experimental and the control groups. The area of inflammation, however, was larger (p less than 0.05) in experimental rats at days 3, 7 and 14. New connective tissue formation was less (p less than 0.05) in sialadenectomized rats at days 14 and 21. The present results indicate that palatal wound healing is altered and delayed in sialadenectomized rats. PMID- 1517482 TI - Thyrotropin-releasing hormone (TRH)-like immunoreactivity in the grey monkey (Macaca fascicularis) spinal cord and medulla oblongata with special emphasis on the bulbospinal tract. AB - The distribution of thyrotropin-releasing hormone (TRH)-like immunoreactivity (LI) has been studied in the grey monkey (Macaca fascicularis) spinal cord and medulla oblongata by the use of indirect immunofluorescence and the peroxidase antiperoxidase (PAP) technique. Furthermore, double-labeling experiments were performed in order to study colocalization of 5-hydroxytryptamine (5-HT)- and substance P-LI. A dense innervation of TRH-immunoreactive (IR) varicose fibers was found in the ventral horn motor nuclei, in the region surrounding the central canal, in the intermediolateral cell column, and in the dorsal horn laminae II and III. In addition, cell bodies harboring TRH-LI were found in the dorsal horn laminae II-IV. In the ventral horn, many of the large cell bodies and their proximal dendrites were totally encapsulated by TRH-IR fibers. From double labeled sections a high degree of coexistence could be established between TRH-/5 HT-LI, TRH-/substance P-LI, and 5-HT-/substance P-LI in fibers in the motor nuclei; as a consequence, a large proportion of these fibers should harbor TRH-/5 HT-/substance P-LI. A coexistence between TRH-/5-HT-LI could also be demonstrated in the intermediolateral cell column. However, no unequivocal coexistence could be found between TRH-/substance P-LI and 5-HT-/substance P-LI in this region. In the dorsal horn, no clear coexistence could be encountered for any of the above indicated combinations. Electron microscopic analysis of material from the lumbar lateral motor nucleus demonstrated TRH-IR terminals making synapses with large cell bodies and dendrites. In addition, contacts lacking synaptic specializations could also be verified. In the medulla oblongata, with the use of the PAP technique, a large number of cell bodies containing TRH-LI were encountered in the midline raphe nuclei and in nucleus reticularis lateralis. A similar distribution pattern could be found for 5-HT-LI, but no cell bodies containing substance P-LI could be seen in these regions. Chemical analysis of specimens from cervical, thoracic, and lumbar spinal cord revealed higher concentrations of TRH- and 5-HT-LI in the ventral quadrants, whereas substance P-LI dominated in the dorsal quadrants. Thus, the concentrations of TRH-, 5-HT-, and substance P-LI was in accordance with the observed regional variation in density of IR-fibers and varicosities found in the spinal cord. We have shown that TRH-LI has a distribution in the monkey spinal cord and medulla oblongata similar to that previously demonstrated in other species.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1517483 TI - Morphology of single vestibulospinal collaterals in the upper cervical spinal cord of the cat: I. Collaterals originating from axons in the ventromedial funiculus contralateral to their cells of origin. AB - Vestibulospinal neurons in the medial and descending vestibular nuclei have widespread bilateral terminations in the upper cervical spinal cord. These terminations arise from axons travelling in several funiculi, including the ventromedial, ventrolateral, lateral, and dorsolateral funiculi in addition to the dorsal columns. The purpose of the present study was to examine the morphology of single vestibulospinal collaterals which terminate in the upper cervical spinal cord and which originate from axons located in one of these funicular pathways, the ventromedial funiculus, contralateral (cVMF) to their cells of origin in the vestibular nuclei. The 32 collaterals described were selected from two separate sets of experiments which took advantage of different techniques. Nineteen of the collaterals were labelled following Phaseolus vulgaris leucoagglutinin (PHA-L) injections into the medial vestibular nucleus and medial regions of the descending vestibular nucleus. The remaining 13 collaterals originated from physiologically identified vestibulospinal axons that were stained after intra-axonal injections of horseradish peroxidase (HRP). The combined projection of all cVMF axon collaterals spread from laminae V to IX, and included the central cervical nucleus. There was a high degree of variability in the pattern of terminations of individual collaterals. This variability was more pronounced among PHA-L-labelled collaterals than HRP-labelled collaterals whose terminations were restricted to laminae VIII and IX. Some PHA-L-labelled collaterals had terminations which were focused within a single lamina, whereas others had termination zones spanning as many as four laminae. The differences between collaterals were compounded when the characteristics of branching patterns were considered. Some collaterals which occupied similar termination zones had different branching structures.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1517484 TI - Morphology of single vestibulospinal collaterals in the upper cervical spinal cord of the cat. II. Collaterals originating from axons outside the ventral funiculi. AB - Recent studies have shown that vestibulospinal axons reach the upper cervical spinal cord of the cat via several different funicular routes. The purpose of this study was to describe the projections of those axons travelling outside the well-recognized pathways in the ventral funiculi. These axons are located in the dorsal columns, dorsolateral funiculi, and lateral funiculi. Collaterals of these axons were stained following extracellular injections of Phaseolus vulgaris leucoagglutinin in the medial and descending vestibular nuclei. The trajectories of individual collaterals were reconstructed from serial histological sections. Collaterals arising from axons in the same funiculus usually had the same characteristic appearance. Axons in the lateral funiculi, ipsilateral or contralateral to their cells of origin, gave rise to collaterals that had a simple structure and usually followed a horizontal trajectory across laminae VII and VIII. The boutons of these collaterals were distributed throughout the mediolateral extent of laminae VI and VII and the dorsal half of lamina VIII. In contrast, axons in the dorsolateral funiculi, ipsilateral or contralateral to their cells of origin, terminated primarily in laminae IV and V. Many collaterals of these axons projected either rostrally or caudally and had a narrow mediolateral distribution. The combined distribution of boutons from collaterals originating from axons in the dorsal columns included the dorsal horn and intermediate zone. Although these collaterals were less common and formed a heterogeneous group, they were easily distinguished from collaterals originating from axons travelling in other funiculi. These results indicate that vestibulospinal axons travelling outside the ventral funiculi comprise several distinct systems. Each system travels by a different funicular route and is distinguished by differences in collateral morphology and termination zones.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1517486 TI - Fos-like immunoreactivity in the brain of homozygous diabetes insipidus Brattleboro and normal Long-Evans rats. AB - Water deprivation induces the production of the transcription factor Fos in neurons of the neurohypophysial system. These neurons, which are located primarily in the hypothalamic paraventricular (PVN) and supraoptic nuclei (SON), produce the antidiuretic hormone vasopressin. The present immunocytochemical study has analyzed the distribution of Fos in brain regions involved in osmoregulation and compared the extent of Fos immunoreactivity (Fos-IR) in vasopressin-deficient Brattleboro and normal Long-Evans rats under stimulated and non-stimulated conditions. Rats were osmotically challenged by means of a single intraperitoneal injection of 1.5 M/L NaCl. Since Fos may be induced by the stress of handling of animals, non-injected and isotonic saline-injected rats were used as controls. Faint nuclear Fos immunostaining was found in the organum vasculosum of the lamina terminalis (OVLT), the median preoptic nucleus (MnPO), subfornical organ (SFO), and SON of non-injected and isotonic saline-injected Brattleboro but not Long-Evans rats. Hypertonic saline injection specifically induced Fos-IR in neurons located in the SFO, OVLT, MnPO, PVN, SON, hypothalamic accessory nuclei (including the nucleus circularis), and arcuate hypothalamic nucleus (Arc) in both Long Evans and Brattleboro rats. No differences in distribution of the induced immunostaining were found between the strains. Stress of handling and (isotonic saline) injection induced Fos-IR in the lateral septal nuclei, central amygdaloid nuclei, medial amygdaloid nucleus, medial preoptic area, the bed nucleus of the stria terminalis, cingulate- and piriform cortex, the lateral hypothalamic area, ventromedial hypothalamic nucleus, and the habenular nucleus. The data are consistent with a role for Fos in the regulation of vasopressin gene expression during acute hyperosmotic stimulation. In addition, this study demonstrated that during chronic osmotic stimulation, as experienced by homozygous Brattleboro rats, Fos-IR is limited but apparently present constantly and that it increased in these animals following acute osmotic challenge. Our observations suggest that c-fos regulatory controls in homozygous Brattleboro rats are different from those in Long-Evans rats. PMID- 1517485 TI - Distribution and characterization of cyclooxygenase immunoreactivity in the ovine brain. AB - Evidence from tissue culture studies suggests that glial cells are the principal source of prostaglandins in the brain. We have used immunohistochemistry, Western blot analysis, and enzyme activity assays to localize cyclooxygenase (COX), the enzyme responsible for the conversion of arachidonic acid to prostaglandins, in situ in the normal ovine brain. We observed very few immunoreactive glial cells. In contrast, an extensive distribution of COX-like immunoreactive (ir) neuronal cell bodies and dendrites and a corresponding pattern of COX enzyme activity were observed. COXir neurons were most abundant in forebrain sites involved in complex, integrative functions and autonomic regulation such as the cerebral cortex, hippocampus, amygdala, bed nucleus of the stria terminalis, substantia innominata, dorsomedial nucleus of the hypothalamus, and tuberomammillary nucleus. Moderate populations were observed in other regions of the central nervous system implicated in sensory afferent processing, including the dorsal column nuclei, spinal trigeminal nucleus, and superior colliculus, and in structures involved in autonomic regulation, such as the nucleus of the solitary tract, parabrachial nucleus, and the periaqueductal gray matter. We did not observe COXir axons or terminal fields, however. Our results suggest that neurons may use prostaglandins as intracellular or perhaps paracrine, but probably not synaptic, mediators in the normal brain. PMID- 1517487 TI - Distribution of GABAergic interneurons immunoreactive for calretinin, calbindin D28K, and parvalbumin in the cerebral cortex of the lizard Podarcis hispanica. AB - The types and distribution of cells containing three calcium-binding proteins, calretinin, calbindin D28K, and parvalbumin, have been studied by immunocytochemistry in different areas of the cerebral cortex of lizards. Cross reactivity of the antisera has been excluded by demonstrating the existence of several cell groups immunoreactive for one but not the other two calcium-binding proteins. In the dorsal and dorsomedial cortices all three proteins coexist in a single subpopulation of gamma-aminobutyric acid (GABA)ergic neurons, the terminals of which form pericellular baskets around cell bodies of bipyramidal neurons. The somata of these neurons are largely restricted to the cellular and inner plexiform layers, but the dendrites usually penetrate all layers, allowing the neurons to sample input from all possible sources. A small number of parvalbumin-containing neurons in the outer plexiform layer do not contain the other two proteins. The medial cortex, which is likely to be homologous to the mammalian dentate gyrus, only contains parvalbumin-immunoreactive neurons. The dendritic trees of these cells appear to avoid the Timm-positive fields receiving input from zinc-rich fiber collaterals, originating from principal cells. The lateral cortex contains calbindin D28K-immunoreactive GABAergic neurons, which lack the other two calcium-binding proteins. These neurons have horizontally running dendrites in the outer plexiform layer, but their axon terminals could not be visualized. The present study uncovered important similarities and differences between the lizard and the mammalian archicortex in the types of neurons containing calcium-binding proteins. As in mammals, different cell types evolved in the lizard to inhibit the perisomatic versus the distal dendritic region of principal cells, the calcium-binding protein-containing neurons being responsible for the former, and neuropeptide-containing neurons for the latter. The results also suggest that further neurochemical diversion of GABAergic interneurons coupled to a functional specialization took place during phylogenetic development from reptiles to mammals. PMID- 1517488 TI - Erythema annulare centrifugum associated with gold sodium thiomalate therapy. AB - Two women with rheumatoid arthritis developed erythema annulare centrifugum while receiving gold thiomalate therapy. Both patients had similar clinical and histologic findings. Results of a lymphocyte stimulation test were positive in one patient but not in the other. PMID- 1517489 TI - Photosensitivity, abnormal porphyrin profile, and sideroblastic anemia. AB - Cutaneous photosensitivity in a 43-year-old man with idiopathic sideroblastic anemia associated with an abnormal porphyrin profile is reported. This condition was associated with elevated free erythrocyte porphyrin, plasma protoporphyrin, urine porphyrins (predominantly coproporphyrin), stool porphyrins (predominantly protoporphyrin), decreased ferrochelatase activity, and deletion of portions of the long arms of chromosomes 18 and 20. Five other patients with sideroblastic anemia and abnormal porphyrin profiles have been described; all but one of these patients had photosensitivity. The porphyrin profile of this patient is similar to that of three other previously described patients. PMID- 1517490 TI - Lipoid proteinosis. AB - Lipoid proteinosis (Urbach-Wiethe disease) is a rare, recessively inherited disorder that is characterized by the deposition of hyaline-like material in the skin, oral cavity, and other tissues. It usually appears in infancy with hoarseness. We report a case of lipoid proteinosis in a 10-year-old boy that demonstrates the characteristic clinical, histologic, and ultramicroscopic features of this disease. PMID- 1517491 TI - Lobular capillary hemangioma (pyogenic granuloma) with satellitosis. AB - We describe a 43-year-old white man who rapidly developed multiple, extensive angiomatous lesions on the temple and scalp after excision of a solitary lobular capillary hemangioma. This is a well-recognized but rare event. Our case differs from previously reported examples in terms of the age of the patient, the location and extent of the lesions, the histologic features in the form of small foci of angiosarcoma-like infiltration, and possibly with respect to the response to therapeutic intervention. Because of the alarming clinical picture produced by multiple lobular capillary hemangiomas, in addition to the occurrence of disturbing histologic features, the benign and self-limited nature of this disease must be emphasized. PMID- 1517492 TI - Eruptive xanthomas during pregnancy. AB - A case of eruptive xanthomas during two successive pregnancies is reported. These xanthomas developed in association with marked hypertriglyceridemia; complications included severe pancreatitis and acute respiratory distress syndrome. This patient most likely had combined familial hyperlipidemia which usually causes only a modest elevation in plasma lipid levels. However, with the added stimulus of estrogens during pregnancy, hypertriglyceridemia and secondary complications developed. PMID- 1517493 TI - Pachydermodactyly: first report in a woman. AB - Pachydermodactyly is a rare form of digital fibromatosis that is characterized by acquired, asymptomatic, protracted connective tissue swellings on the back and sides of a few proximal phalanges or proximal interphalangeal joints. This is the tenth reported case of pachydermodactyly. It has previously been reported only in men; to the best of our knowledge, this is the first woman described with this condition. PMID- 1517494 TI - Papulonodular dermal mucinosis in lupus erythematosus. AB - We report two cases of lupus erythematosus (LE) in which a truncal papulonodular eruption predominated. Histologically the lesions were characterized by diffuse dermal mucin without the usual inflammatory or epidermal changes of LE. It is uncommon in LE for dermal mucin to be present in a sufficient quantity to produce a papulonodular eruption in the absence of typical epidermal changes. PMID- 1517495 TI - Linear unilateral basaloid follicular hamartoma. AB - A 36-year-old woman with a linear and unilateral cutaneous hamartoma is described. The lesions consisted of hypopigmented macules that coalesced into a linear plaque that involved only the left side of her body. Within this plaque were several pearly papules and an ulcerated area that clinically resembled basal cell carcinomas. Histologic features of the hypopigmented linear plaque included multiple and multifocal basaloid proliferations in the papillary and mid dermis. The isolated pearly papules showed the typical findings of basal cell carcinoma. PMID- 1517496 TI - Generalized perforating granuloma annulare. AB - Generalized perforating granuloma annulare is characterized by 1 to 4 mm umbilicated papules on the extremities, and is most commonly seen in children and young adults. Transepithelial elimination of mucinous, degenerating collagen fibers and surrounding palisading lymphohistiocytic granulomas are important histologic features. Perforating sarcoidosis and perforating granuloma annulare may be difficult to differentiate because of a similar clinical appearance and the presence of sarcoidal granulomas in biopsy specimens. A particularly high incidence of perforating granuloma annulare has been reported in the Hawaiian Islands. PMID- 1517497 TI - Rapp-Hodgkin ectodermal dysplasia. AB - Rapp-Hodgkin syndrome is a rare condition that is characterized by ectodermal dysplasia and palatal abnormalities. We describe a 24-year-old white woman who has Rapp-Hodgkin syndrome that is associated with a chronic palmar keratoderma, which is a finding that has not been previously reported. We review the literature, assign the clinical features into major and minor categories, and suggest therapeutic interventions to limit the significant sequelae of this autosomal dominant syndrome. PMID- 1517499 TI - Angiomyolipoma. AB - Angiomyolipoma is a benign tumor, usually of the kidney, that is frequently associated with tuberous sclerosis. Extrarenal tumors are rare. Cutaneous lesions have only recently been reported. We report a case of cutaneous angiomyolipoma with results of clinical, histologic, and immunohistochemical evaluation. PMID- 1517498 TI - Cutaneous T-cell lymphoma with porokeratosis-like lesions. AB - We describe two black patients who had widespread, sharply demarcated, round, hyperpigmented or hypopigmented macules that clinically resembled disseminated superficial actinic porokeratosis (DSAP). One patient was known to have cutaneous T-cell lymphoma (CTCL), and the other patient had only the DSAP-like lesions. Histopathologic and immunohistochemical studies of the DSAP-like lesions revealed characteristic features of patch-phase CTCL. This unusual variant of patch-phase CTCL should be differentiated from DSAP and the hypopigmented variant of CTCL. PMID- 1517500 TI - Generalized nodular cutaneous pseudolymphoma associated with phenytoin therapy. Use of T-cell receptor gene rearrangement in diagnosis and clinical review of cutaneous reactions to phenytoin. AB - The first reported case of phenytoin-induced generalized nodular cutaneous pseudolymphoma without symptoms of the phenytoin hypersensitivity syndrome is presented. Despite the malignant histologic appearance of the dermal infiltrate, T-cell receptor gene rearrangement studies did not demonstrate monoclonality. The cutaneous nodules resolved within 2 weeks after discontinuation of phenytoin therapy. The literature is reviewed with regard to the spectrum of cutaneous reactions to phenytoin and particularly with regard to the occurrence of lymphoma, pseudolymphoma, and phenytoin hypersensitivity syndrome. We suggest the use of T-cell receptor gene rearrangement studies in similar situations of phenytoin hypersensitivity syndrome and lymphadenopathy. A brief period of discontinuation of the drug will demonstrate the regression associated with benign lymphoproliferation and will forestall needless treatment. PMID- 1517501 TI - Toxic epidermal necrolysis in early infancy. AB - Toxic epidermal necrolysis (TEN) is a life-threatening bullous dermatosis characterized by the sudden onset of full-thickness epidermal necrosis. TEN is a disease of both children and adults, but TEN in early infancy is a rare event; only two well-documented cases in infants less than 6 months of age have been reported. We report a third case of a 6-week-old infant with Escherichia coli sepsis who received ampicillin and other antibiotics and subsequently developed TEN. Despite the withdrawal of ampicillin and aggressive systemic and wound care, the infant died. The infants in the other two reported cases also died, which suggests that TEN in early infancy has an extremely poor prognosis. PMID- 1517502 TI - Annular epidermolytic ichthyosis: a unique phenotype. AB - A 30-year-old white woman developed bullous and ichthyosiform skin lesions at the age of 8 months. Blistering ceased at puberty, but the hyperkeratotic plaques persisted. She subsequently delivered five children, two of whom were affected with a bullous type of ichthyosis. At the age of 27 years, she developed numerous annular and polycyclic, erythematous, hyperkeratotic plaques on the trunk and extremities that were pruritic, enlarged slowly, and then resolved. Histopathologic examination of these annular plaques revealed epidermolytic hyperkeratosis. Electron microscopic examination of the annular plaques showed interrupted perinuclear tonofilament rings consistent with either bullous ichthyotic erythroderma of Brocq or ichthyosis bullosa of Siemens. This kindred may represent a new phenotype of epidermolytic (acanthokeratolytic) ichthyosis. PMID- 1517503 TI - Fatal pyoderma gangrenosum in association with C7 deficiency. AB - Although pyoderma gangrenosum (PG) is often associated with systemic diseases, it has not been reported in association with congenital complement deficiencies. We describe an aggressive and ultimately fatal case of PG in a patient with a congenital C7 deficiency. Deficiencies of C7 can be associated with decreased neutrophil chemotaxis, phagocytosis, and opsonization, similar to the immunologic abnormalities described in patients with PG. Our patient's decreased complement level, if not directly related to the development of PG, may have contributed to the aggressive nature of her disease. PMID- 1517504 TI - Effect of synergists on the oral and topical toxicity of azamethiphos to organophosphate-resistant houseflies (Diptera: Muscidae). AB - Dermal and oral toxicities of azamethiphos were determined in two organophosphate resistant and one susceptible strain of houseflies, Musca domestica L. The 594vb strain was 1,967-fold more resistant to azamethiphos when compared with the susceptible Chemical Specialties Manufacturers Association (CSMA) strain by dermal application. When the compound was administered orally to the 594vb strain, we observed only a 15-fold resistance. In contrast, the Yachiyo strain, which show 1,500-fold resistance to diazinon and which has known multiple mechanisms for organophosphate resistance, showed only 6-fold resistance to azamethiphos by topical application and 4-fold resistance by oral administration. Azamethiphos administered dermally and orally was equally toxic to the CSMA and Yachiyo strains. However, when azamethiphos was administered to the 594vb strain, the insecticide was 71 times more toxic orally than by the dermal route. This result indicated involvement of a cuticular penetration factor in the resistance mechanism. The effect on azamethiphos toxicity of piperonyl butoxide (PB), an inhibitor of the monooxygenases, and tributylphosphorotrithioate (DEF), an esterase inhibitor, was investigated in the three strains. Pretreatment of the flies with PB, DEF, or PB+DEF before topical application of azamethiphos resulted in a significant decrease in LD50s in all the strains. The degree of synergism, however, varied depending upon the strains and the synergists. Similar results were obtained when azamethiphos was administered orally following pretreatment of the flies with PB+DEF. We attribute the high level of azamethiphos resistance in the 594vb strain partly to increased degradation by oxidative and hydrolytic enzymes. The hydrolytic enzymes are more important, but other factors including reduced cuticular penetration and insensitive acetylcholinesterase may be involved.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1517505 TI - Biochemical characterization of hydrolytic and oxidative enzymes in insecticide resistant and susceptible strains of the German cockroach (Dictyoptera: Blattellidae). AB - We have identified resistance mechanisms in the German cockroach, Blattella germanica (L.), for propoxur and chlorpyrifos in strains of cockroaches that display multiresistance to several organophosphate and carbamate insecticides. The resistance mechanisms involve the combined effects of increased oxidative and hydrolytic metabolism and both strains are resistant to chlorpyrifos and propoxur. Experiments designed to test for similarity in metabolic enzymes suggest that, although the mechanisms involve similar processes, the enzymes responsible for insecticide detoxification are different in the two strains. Both resistant strains exhibited enhanced activity toward alpha-naphtholic esters relative to a standard susceptible strain; however, analysis of the progeny from resistant X susceptible crosses suggests that this general esterase activity is inherited differently than propoxur or chlorpyrifos resistance. Hybrids of the propoxur-resistant strain displayed the highest activity of all cockroaches tested, in contrast to hybrids of the chlorpyrifos-resistant strain, which were similar to the susceptible strain. Native gel electrophoresis of cytosolic preparations provided further evidence for differences in the pattern of hydrolytic enzymes and inheritance of resistance in the two strains. Analysis of components of the cytochrome P450-dependent monooxygenase system and activities toward model substrates indicate that the two resistance mechanisms also involve different oxidative processes. The propoxur-resistant strain displayed significantly higher levels of total cytochrome P450, but no other components were correlated with resistance. In contrast with the chlopyrifos-resistant strain, which was similar to the susceptible strain in all parameters measured, activity toward model substrates was higher in the propoxur-resistant strain than in any of the other strains and hybrids tested.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1517506 TI - Field tests of an acephate baiting system designed for eradicating undesirable honey bees (Hymenoptera: Apidae). AB - Field evaluations were made of a baiting system designed for use by regulatory agencies in suppressing populations of undesirable feral honey bees, Apis mellifera L. (e.g., bees posing hazards [especially Africanized bees] and colonies infested with parasitic mites). Bees from feral or simulated feral (hived) colonies were lured with honey and Nasonov pheromone components to feeders dispensing sucrose-honey syrup. After 1-3 wk of passive training to feeders, colonies were treated during active foraging by replacing untreated syrup with syrup containing 500 ppm (mg/liter) acephate (Orthene 75 S). In four trials using hived colonies on Grant Terre Island, LA., 21 of 29 colonies foraged actively enough at baits to be treated, and 20 of the 22 treated were destroyed. In the lower Rio Grande Valley of Texas (two trials at each of two trials), treatments killed 11 of 16 colonies (6 of 10 hived; 50 of 6 feral). Overall results showed that all 11 colonies that collected greater than 25 mg acephate died, whereas 3 of 10 colonies receiving less than 25 mg survived. Delivering adequate doses required a minimum of approximately 100 bees per target colony simultaneously collecting treated syrup. The system destroyed target colonies located up to nearly 700 m away from baits. Major factors limiting efficacy were conditions inhibiting foraging at baits (e.g., competing natural nectar sources and temperatures and winds that restricted bee flight). PMID- 1517507 TI - Performance of gel and paste bait products for German cockroach (Dictyoptera: Blattellidae) control: laboratory and field studies. AB - Gel and paste bait formulations containing boric acid or hydramethylnon were evaluated in field and laboratory experiments with the German cockroach, Blattella germanica (L.). Bait formulations contained 14-62% water by weight and lost the most water after 1 d of desiccation. Bait age and water content did not alter the toxicity (LT50) of boric acid-based baits. Toxicity of hydramethylnon (Maxforce) bait, however, increased with bait age. In continuous exposure tests without harborage, boric acid formulations had LT50s of 8.5 and 10.1 d for Blue Diamond and IT WORKS, respectively. Maxforce bait had an LT50 of 4.2 d. LT50s determined with cardboard harborage or in Ebeling choice boxes were 1.5 to 2.2 times lower than those from continuous exposure tests without harborage. Relative repellency, measured as the mean percent of live cockroaches in the light side of the choice box, was greatest for IT WORKS (21.4%) and Maxforce (25.4%) formulations, followed by Blue Diamond (10.9%). A performance index that combined choice box repellency and mortality data indicated that Maxforce had the greatest potential for field effectiveness. Blue Diamond and Maxforce significantly reduced German cockroach populations in the field. Maxforce performed best in field trials when applied at 10 or 20 placements per apartment. Apartments treated with IT WORKS had significantly greater cockroach trap catches. Factors that may affect the predictive power of the performance index are discussed. PMID- 1517508 TI - Susceptibility of cockroaches (Dictyoptera: Blattellidae, Blattidae) to infection by Steinernema carpocapsae. AB - The susceptibility of American cockroaches, Periplaneta americana (L.); smoky brown cockroaches, P. fuliginosa (Serville); oriental cockroaches, Blatta orientalis L.; German cockroaches, Blattella germanica (L.); and brownbanded cockroaches, Supella longipalpa (F.), to Steinernema carpocapsae Weiser (All strain) was evaluated under laboratory conditions. A 1-ml water suspension containing 500,000 nematodes was placed on filter paper in a petri dish or the pad of a bait station. German, brown-banded, oriental, and smoky-brown cockroaches died within 1 d after placement in the petri dishes. The relative order for the LT50s were American greater than oriental greater than smoky-brown greater than brown-banded = German. All cockroaches actively groomed nematodes from legs and antennae of forced (petri dish) exposure. The LT50s for S. carpocapsae for nonforced (bait station) exposure were significantly greater than those for forced exposure. The LT50s were 3.25, 4.13, 9.86, and 11.38 d for brown banded, German, oriental, and smoky-brown cockroaches, respectively. The relative order of the LT50s after forced (American greater than oriental greater than smoky-brown greater than German = brown-banded) and nonforced (American greater than smoky-brown greater than oriental greater than German greater than brown banded) exposure to S. carpocapsae was inversely related to the moisture of their preferred habitats. PMID- 1517509 TI - Oral toxicity, formulation effects, and field performance of flufenoxuron against the German cockroach (Dictyoptera: Blattellidae). AB - Laboratory and field studies on the benzoylphenyl urea (BPU) chitin synthetase inhibitor flufenoxuron (DPX EY-059) showed great potential for its use in suppressing infestations of German cockroach, Blattella germanica (L.). When fed continuously to fifth (last) instars, the LC50 of flufenoxuron was estimated at 0.82 ppm (95% FL, 0.76-0.87 ppm). A rating scale specific for BPU effects was developed and shown to be positively correlated with the insect's exposure to concentration of flufenoxuron. Manipulating the particle size of wettable powder formulations of flufenoxuron significantly altered their activity in contact bioassays. Larger particles (volume mean diameter, 12.2 mu; range, 10-20 mu) were more active. Field trials in multifamily housing with this wettable powder formulation at 0.033 and 0.066% (AI) achieved high level (greater than 80%) population suppression within 8 wk of treatment. The potential for the use of flufenoxuron in B. germanica management programs is discussed. PMID- 1517510 TI - Strain differences in the response of German cockroaches (Dictyoptera: Blattellidae) to emulsifiable concentrates. AB - The response of a susceptible and two pyrethroid-resistant field strains of the German cockroach, Blattella germanica, to four emulsifiable concentrates (ECs)- Tempo (cyfluthrin), Demon (cypermethrin), Dursban (chlorpyrifos) LO, and XRM 5184 (chlorpyrifos)--was investigated. Application rates were 0.4, 0.1, 0.5, and 0.5%, respectively. Susceptible cockroaches avoided dried formulations of the pyrethroids Tempo and Demon, but resistant cockroaches did not; avoidance was greater with Demon than with Tempo. Filter papers freshly impregnated (wet) with Demon and Tempo flushed susceptible cockroaches (Demon greater than Tempo). Resistant cockroaches were flushed only by Demon, but less so than susceptible strain cockroaches. No mortality occurred in experiments with the pyrethroids. Dried formulations of Dursban LO and XRM 5184 had little, if any, repellency to nymphs of either the susceptible or resistant strains. Initially (1-3 h), most cockroaches settled on treated papers. Subsequent movement off treated papers was a step in the process leading to knockdown. At 24 h, mortality of susceptible cockroaches was 100% in the experiment with Dursban LO and 95% in the experiment with XRM 5184. Highest mortality in a resistant strain (40%) was in the contact experiment with Dursban LO. In contact repellency and flushing experiments, mortality was higher with Dursban LO than with XRM 5184. Neither chlorpyrifos formulation flushed cockroaches effectively. Mortality in flushing experiments was less than in the contact repellency experiments. PMID- 1517511 TI - Fee-for-service. PMID- 1517512 TI - How much is enough. PMID- 1517513 TI - National Commission on AIDS rejects mandatory testing, disclosure. PMID- 1517514 TI - Case shows caution critical on referrals. PMID- 1517515 TI - A computer database approach for dental practice. PMID- 1517516 TI - Improving bond strength through acid etching of dentin and bonding to wet dentin surfaces. AB - A bonding system using moisture on the tooth surface can be an enormous benefit as obtaining dentin dryness in the mouth is nearly impossible. The author describes a system that bonds to both wet and dry surfaces. PMID- 1517517 TI - Recognizing and reporting victims of domestic violence. AB - Domestic violence can be defined as any violent behavior directed against an individual within the home or family. It occurs in all segments of society and is not limited to a single ethnic or socioeconomic group. Since most intentional injuries occur in the head and neck area, the dentist might be the first to treat the domestic violence victim. PMID- 1517518 TI - The dental hygiene story--one more chapter. PMID- 1517519 TI - Preventing local anesthesia toxicity. PMID- 1517520 TI - A look at state-of-the-art tooth-colored inlays and onlays. PMID- 1517521 TI - Computer viruses: a valid threat for the health care professional? AB - The probability of a virus infecting a health care professional's computer is minimal if prevention is used. However, all office personnel who access the computer must be educated with what to look for, what to do and what not to do when a computer virus is suspect. PMID- 1517522 TI - Plotting the investment yield curve. PMID- 1517523 TI - Dental licensure. PMID- 1517524 TI - Principles of ethics and code of professional conduct with official advisory opinions revised to May 1992. AB - The ethical statements which have historically been subscribed to by the dental profession have had the benefit of the patient as their primary goal. Recognition of this goal, and of the education and training of a dentist, has resulted in society affording to the profession the privilege and obligation of self government. The Association calls upon members of the profession to be caring and fair in their contact with patients. Although the structure of society may change, the overriding obligation of the dentist will always remain the duty to provide quality care in a competent and timely manner. All members must protect and preserve the high standards of oral health care provided to the public by the profession. They must strive to improve the care delivered--through education, training, research and, most of all, adherence to a stringent code of ethics, structured to meet the needs of the patient. PMID- 1517525 TI - Enhancement of polymorphonuclear cell phagocytosis by lipid A-activated monocytes via cell-to-cell contact. A possible role for membrane-associated cytokines. AB - Previous findings have shown that lipopolysaccharide (LPS)-activated human monocytes express cytokines (CKs) on their membrane. Furthermore, those associated to membrane products such as tumor necrosis factor (TNF)-alpha and interleukin (IL)-1 have been demonstrated to exert many biological activities. In this paper, evidence is provided that human polymorphonuclear cells (PMN) exhibited an increased phagocytic capacity following incubation with either lipid A (LA)-activated autologous monocytes or supernatants recovered from LA stimulated mononuclear cell cultures. In order to investigate the possible role of monocyte membrane-associated TNF-alpha, IL-1 alpha and IL-1 beta in the modulation of PMN activity, in a separate series of experiments LA-activated monocytes or LA-activated supernatants were pretreated with anti-recombinant human (Rhu) TNF alpha, anti-Rhu IL-1 alpha and anti-Rhu IL-1 beta monoclonal antibodies (MoAbs), respectively. Such an approach gave rise to an abrogation of monocyte-mediated triggering effect on PMN functional capacity. Taken together, these data suggest that activated monocytes can upregulate PMN phagocytosis by a cell-to-cell contact mechanism, likely related to membrane-associated CKs. PMID- 1517526 TI - Immunological consequences of zidovudine treatment in control and morphine or methadone treated mice. AB - The effects of acute and chronic zidovudine (AZT) administration on immunologic test responses of mice were studied. The effects of AZT administration combined with morphine or methadone treatment, were also studied separately comparing the effects of each drug. We noted that AZT-treatment did not modify the T-lymphocyte subsets (L3T4/LyT2 rate), whereas morphine-treatment and AZT plus morphine treatment decreased the percentage of T helper cells. Acute and chronic AZT treatment increased Natural Killer cell (NK) activity and also recovered the decreased NK cell activity produced by morphine-treatment. AZT-treatment, morphine-treatment, AZT plus morphine treatment and AZT plus methadone treatment strongly depressed the phagocytic physiological activity of Polymorphonuclear leukocytes (PMNs). Another evidence of immunologic responsiveness against AZT was the reduction of the mitogenic and antigenic response of lymphocytes. These results suggest a negative role of AZT-treatment especially on phagocytic activity and confirms a depressive effect of morphine-treatment on several immune functions studied. Furthermore, there is no indication of additive or synergistic toxic effects of AZT, morphine and methadone on the immune functions above that seen with each of these drugs when tested alone. PMID- 1517527 TI - Effect of a traditional Chinese medicine, bu-zhong-yi-qi-tang (Japanese name: Hochu-ekki-to) on the protection against Listeria monocytogenes infection in mice. AB - Effects of Bu-Zhong-Yi-Qi-Tang (Japanese name: Hochu-ekki-to) on the resistance against Listeria monocytogenes were observed in ICR mice orally administered this medicine daily for 10 days. Survival rates were increased by the pretreatment in mice inoculated i.v. with bacteria 1 day after the last administration and in mice inoculated i.p. 4 days after the last administration. After an i.v. inoculation of L. monocytogenes, the numbers of bacteria in the spleen and liver increased gradually to kill mice by day 5 in untreated group but the bacterial numbers increased slightly by day 3 and decreased from day 3 to day 8 in Hochu ekki-to pretreated group. After an i.p. inoculation, the number of bacteria in the peritoneal cavity decreased very rapidly within 6h in Hochu-ekki-to treated group compared to that in untreated group. After the administration, number of polymorphonuclear cells increased in the peripheral blood, peritoneal cavity and spleen. In treated mice, macrophages increased in number in the peritoneal cavity and the spleen but decreased in the peripheral blood. Peritoneal macrophages from treated mice showed an enhanced activity to kill L. monocytogenes in vitro within 60 min after ingestion of bacteria. Hochu-ekki-to may augment the host defense against L. monocytogenes through the activation of macrophage series during an early phase of infection. PMID- 1517528 TI - Augmentation of mitogen-induced interleukin 2 production by oral administration of polysaccharide SPR-901. AB - The effects of oral administration of antitumor polysaccharide SPR-901 (RBS), an alpha-1,3 branched alpha-1,6 glucan, on concanavalin A (Con A)-induced interleukin 2 (IL-2) production of splenocytes were studied. The augmentation effect on Con A-induced IL-2 production was evident when more than 30 mg/kg of SPR-901 was administered orally to mice. On the other hand, oral administration of B512 dextran, an analogous alpha-1,6 glucan, did not show any augmentation effects on IL-2 production. The augmentation effect of SPR-901 on IL-2 production seemed to be mediated mainly by macrophages stimulated with SPR-901. PMID- 1517529 TI - Anesthetic agents induce human mononuclear leucocytes to release cytokines. AB - Studies were carried out on the ability of some anesthetic agents (Propofol, Dormicum, Ketalar and Penthotal) to induce the release of cytokines by human monocytes and lymphocytes in vitro. All anesthetic agents tested at hematic concentrations reached during anesthetic administration cause an increase in the production of Tumor necrosis factor (TNF) from human monocytes; the increase is 4 5 times greater than controls. The greatest Interleukin -1 alpha (IL-1 alpha) production increase was induced by Propofol. The release of Interleukin -6 (IL-6) is notably increased by Ketalar (about 10 times greater than controls). In the presence of different anesthetic agents, human lymphocytes release Interleukin -4 (IL-4) and Interferon gamma- (IFN-gamma). Penthotal and Ketalar increase IL-4 production which appears quite high compared to that obtained with Con A used as standard challenge. Propofol induce IL-4 release which is about the same as that seen with Con A. IFN-gamma is released in high quantities by lymphocytes treated with Propofol. Dormicum, Ketalar and Penthotal induce non-significant increase of IFN-gamma release. The results concern the choice of anesthetic, in relation to its action on host immune response. This aspect is particularly interesting in immunocompromised host. PMID- 1517530 TI - Serum tumor necrosis factor activity in inflammatory bowel disease. AB - Serum tumor necrosis factor (TNF) levels in 33 patients with inflammatory bowel disease (IBD) were measured by using a sensitive enzyme immunoassay. Four of five Crohn's diseases (CD) and nine of twenty eight ulcerative colitis (UC) had elevated levels of serum TNF. In active CD or UC, a greater fraction of patients studied had significantly increased serum TNF levels (3/3 for CD and 8/11 for UC). Production of TNF by peripheral blood monocytes when stimulated by lipopolysaccharide was also increased in these patients and correlated with their serum TNF levels. These results suggest that TNF may have some pathoetiological meaning in IBD. PMID- 1517531 TI - Nicotine enhances interleukin production of rat splenic T lymphocytes. AB - Very little is known regarding the effects of nicotine, the most pharmacologically active component of tobacco products, on T lymphocyte activity or interleukin production. Therefore, rats were implanted subcutaneously with osmotic mini-pumps containing either physiological saline, nicotine (1.5 mg/kg/day) or a high dose of nicotine (4.5 mg/kg/day) for a period of 14 days. The ability of the splenic T lymphocytes to respond to the polyclonal T lymphocyte mitogens, Concanavalin A (ConA) or phytohemagglutinin (PHA), and the ability of mitogen stimulated splenic T lymphocytes to produce interleukin 2 (IL2) were determined. Treatment with nicotine suppressed, in a dose dependent fashion, the ability of splenic T lymphocytes to respond to mitogen, but dramatically enhanced the ability of mitogen stimulated lymphocytes to generate IL2. PMID- 1517532 TI - Effects of famotidine on various immunological parameters in patients with rheumatic diseases: decreased lymphocyte DR expression by famotidine. AB - We examined the effect of famotidine, a histamine-type 2 receptor antagonist, on the immunocompetent cells. The number of DR(+) cells were significantly decreased in patients with systemic lupus erythematosus (P less than 0.05) by parenteral administration of famotidine (40 mg/days for 4 weeks). However, total lymphocyte number and monocyte number did not change. Immunoglobulin levels of patients with rheumatoid arthritis and normal male did not change. Furthermore, phytohemagglutinin induced lymphocyte proliferation was increased by addition of famotidine (10 ng/ml). Nonetheless, famotidine did not have mitogenic function itself to lymphocyte and did not affect IL-2 production. PMID- 1517533 TI - Immunotoxic effects of mercuric compounds on human lymphocytes and monocytes. I. Suppression of T-cell activation. AB - Considerable attention has been directed at defining the health deficits associated with exposure to mercurial compounds. While numerous studies have been conducted, the findings have been somewhat contradictory and have led to a confused understanding of the immunotoxicology of mercury. It is becoming clear, however, that the immunotoxic effects of heavy metals in general, and mercury in particular, are dependent upon the assays and source of cells. The major goal of our study was to assess whether low level mercury exposure modulates human T-cell function. Following treatment of T-cells with HgCl2 (0-1000 ng) and MeHgCl (0-100 ng), their activation by mitogens was evaluated. Both forms of mercury caused a dose dependent reduction in T cell proliferation, however, the effect was dependent upon the presence of monocytes. Moreover, in the absence of monocytes, HgCl2 enhance PMA induced T-cell proliferation. MeHgCl was approximately 5-10 times more potent than HgCl2. Mercury also inhibited the ability of these cells to synthesize and secrete IL-1. Analysis of the expression of activation markers on the cell surface indicated that one of the earliest markers of lymphocyte activation, CD69, was not effected by mercury. In comparison, T-cell expression of IL-2R and the transferrin receptor was impaired. Of particular interest, cells activated by mitogen for 24 hr became refractory to the immunotoxic effects of mercury. The results of this investigation clearly show that mercury-containing compounds are immunomodulatory; moreover, the decrease in T-cell function following exposure to mercury indicates that this metal is immunotoxic at very low exposure levels. PMID- 1517534 TI - Immunotoxic effects of mercuric compounds on human lymphocytes and monocytes. II. Alterations in cell viability. AB - The major goal of this investigation was to examine the cytotoxic properties of both HgCl2 and MeHgCl, in terms of their ability to alter human T-cell and monocyte viability. Following treatment with HgCl2 (0-20 micrograms/ml) or MeHgCl (0-2 micrograms/ml), there was minimal reduction in lymphocyte viability at 1-4 hr. However, after exposure to mercury for 24 hr, cell death was apparent. In comparison, monocytes exhibited significant loss of viability during the early exposure periods. MeHgCl was approximately 5-10 times more potent than HgCl2. Other indicators of cell death were also determined. Measurement of the energy charge ratio indicated profound changes in cellular energy conservation. Electron microscopic analysis of cells treated with mercury revealed early nuclear alterations characterized by hyperchromaticity, nuclear fragmentation and condensation of nucleoplasm. In concert with these nuclear changes, there was destruction of cytoplasmic organelles with loss of membrane integrity. Studies of phospholipid synthesis by mercury treated cells confirmed that there were alterations in membrane structure. Thus, there was a decrease in total phosphatide synthesis by treated cells. Moreover, monocyte phospholipid synthesis appeared to be more sensitive to the presence of mercury then lymphocytes. Finally, both forms of mercury caused a rapid and sustained elevation in the intracellular levels of Ca++. These morphological and biochemical changes are consistent with the notion that mercury initiates cytotoxic changes associated with programmed cell death. PMID- 1517535 TI - Effect of human IgG1 peptides on the antigen-specific antibody response of mice in vivo. AB - The effect of synthetic peptides--corresponding to the amino acid sequences 289 301 (Y48) and 293-301 (Y91) within the CH-2 domain in the human IgG1 was studied on the oxazolone-specific primary and secondary antibody response isotype distribution and on the sheep erythrocyte (SRBC)-specific primary IgM response. High responder (Balb/c) and low responder (C57Bl/6) mice to oxazolone hapten were treated intraperitoneally with various doses of peptides simultaneously with the first and second contact sensitization. The relative levels of oxazolone-specific IgM, IgG3, IgG1, IgG2a and IgG2b antibodies were determined by a solid phase radioimmunoassay. Y48 and Y91 peptides in a dose range of 10(-5) - 10(-8) M/animal enhanced the oxazolone-specific antibody response. This effect was more striking under suboptimal conditions: using smaller antigen dose for sensitization, cyclophosphamide pretreatment or using genetically low responder mice. SRBC-specific primary IgM response was enhanced by Y91 peptide, Y48 was ineffective. PMID- 1517536 TI - Chemotactic activities of peripheral blood polymorphonuclear leukocytes and peritoneal exudate polymorphonuclear leukocytes in MRL mice. AB - Chemotactic responsiveness to fMet-Leu-Phe in concentrations of 10(-8) to 10(-4) M in the Boyden chamber was compared between peritoneal exudate cells (PEC) and polymorphonuclear leukocytes (PMN) isolated from peripheral blood, between MRL/Mp +/+ (MRL-+/+) and MRL/Mp-lpr/lpr (MRL-lpr/lpr) mice, and between young (6-9 week old) and aged (16-24 week old) mice. Chemotactic responsiveness of PEC did not differ between MRL-+/+ and MRL-lpr/lpr, and young and aged mice. While, PMN showed greater chemotaxis in aged MRL-+/+ mice than that in aged MRL-lpr/lpr mice. These results suggest that chemotactic responsiveness of PMN differ from that of PEC which is assumed to be preactivated by an inflammatory agent injected into the peritoneal cavity to elicit cells. Less responsiveness of PMN to the bacterial origin peptide might relate to the autoimmune disease of this murine model. PMID- 1517538 TI - Differential effects of morphine and naltrexone on the antibody response in various mouse strains. AB - Morphine treatment has been shown to suppress several immunologic parameters. In this study, we examined the effects of morphine pellet implantation in vivo on the primary antibody response measured in vitro in various mouse strains. Effects of mouse strain and sex on morphine-induced suppression of the plaque-forming cell response, as well as spleen weight and mortality were determined. Morphine suppressed the primary antibody response in C3HeB/FeJ, C3H/HeJ and C57Bl/6 mice, while Balb/cByJ and the mu-receptor-deficient strain CxBk/ByJ mice were not affected. There was no difference in the response to morphine between male and female C3HeB/FeJ mice. Naltrexone reversed the morphine-induced suppression in the C3H strains, but not in C57Bl/6 mice. In addition, naltrexone caused significant mortality in Balb/cByJ mice. Spleen weight was decreased by morphine treatment in all the strains, but only the C3H strains were sensitive to the lethal effects of morphine. Thus, immune suppression did not correlate with splenic atrophy or mortality. The strain differences in response to chronic morphine and naltrexone treatment suggest that morphine may be acting through both opioid and non-classical opioid (e.g., not blocked by naltrexone) mechanisms. PMID- 1517537 TI - Expression of c-fos and c-myc oncogenes in the P388D1 murine macrophage line treated by immunomodulators: absence of direct correlation with DNA synthesis. AB - Complex patterns of metabolic and functional characteristics are induced in macrophages by biological response modifiers. The study of the early events resulting from the transduction of immunomodulatory signals could be an approach for a better understanding of this activation process. The transcription of c-fos and c-myc genes has been shown to be rapidly modified in many cells responding to various signals. Since murine peritoneal macrophages are a rather heterogeneous population we chose to investigate the c-fos and c-myc modulation in the P388D1 murine macrophage line. Owing to the frequent implication of the c-myc gene in the tumorigenicity of hematopoietic cells we first demonstrated the normal c-myc status in this cell line by Southern analysis. The modulation of the c-fos and c myc expression has been studied by Northern analysis, 15, 30 and 60 minutes after treatment of the P388D1 cells by the phorbol ester (TPA), the Calcium ionophore A 23187 (Ca2+I), the N-acetyl muramyldipeptide (MDP) or the macrophage Colony Stimulating Factor (CSF-1). The mitogenic activity of these compounds, as evaluated by [3H] thymidine incorporation, has been measured either after a 30 minute or a 24 hour treatment. An early increase in c-fos expression always preceded a c-myc augmentation. The highest modulation of c-fos and c-myc was observed with TPA. Ca2+I and TPA presented a low mitogenic effect if compared to CSF-1. MDP did not change DNA synthesis even after 24 hours. Therefore, in the present study on the P388D1 macrophage cell line, no direct correlation could be evidenced between the mitogenic effect and the modulation of c-fos and c-myc induced by these immunomodifiers. Investigations are in progress in order to evaluate the role of these proto-oncogenes on terminal differentiation induced by immunomodulators in this cell line. PMID- 1517539 TI - Continuous infusion of endotoxin depresses splenic blastogenesis. AB - Continuous infusion of a sublethal dose of bacterial endotoxin into rats via an implanted osmotic pump markedly affected the blastogenic responsiveness of spleen cells to specific endotoxin as well as to the nonspecific mitogens Con A, PHA or PWM. There was also a marked alteration in lymphoid cell type and number in the spleen of the rats after continuous infusion of endotoxin, with a marked increase in plasma cell infiltration and germinal center formation. There was no significant alteration in glucocorticoid steroid levels. Control rats given saline only for a period of seven days via an implanted pump showed no or minimal effect for the first 5 days and then a delayed depression of blastogenic responses to LPS and to Con A, but this time lag contrasted markedly to the much earlier unresponsiveness of splenocytes from rats infused with endotoxin. Only a slight to moderate cellular infiltration occurred in the spleen of control rats implanted with a pump infusing saline only or an empty pump. Thus endotoxin infusion in a continuous manner via an implanted pump accounted for the early and marked suppression of responsiveness, as well as alteration in spleen size and cellularity. PMID- 1517540 TI - A small outbreak of spontaneous abortion in four patients from two households. PMID- 1517541 TI - Parenteral versus oral antimicrobials. PMID- 1517542 TI - Streptococcus salivarius meningitis following myelography. PMID- 1517543 TI - Wound infection rates following clean operative procedures: can we assume them to be low? PMID- 1517544 TI - Wound infection rates in clean surgery: a potentially misleading risk classification. AB - OBJECTIVES: To evaluate the incidence of wound infection in inguinal hernioplasties, incisional hernioplasties, splenectomies, and splenectomies performed in patients with hepatosplenic schistosomiasis, and to examine the relationship of surgical wound infection to antibiotic use, patient age, length of stay in the hospital prior to surgery, and the duration of the operation. DESIGN: Retrospective surveillance study. RESULTS: One thousand five hundred forty-two clean operations were analyzed. Comparing response (wound infection) and explanatory variables (age, length of hospital stay, duration of surgery, antibiotics, and surgery type), we found that age, use of antibiotics, and type of surgery were statistically significant, while length of hospital stay and duration of surgery were not significant. CONCLUSIONS: From these results, we can predict that the probability of wound infection in surgical patients considering these significant variables is lower for patients ages 14 to 30 years and higher for patients ages 31 to 60 years and lower for patients with prophylactic antibiotic use (up to 72 hours of use) and higher for patients with prolonged use (more than 72 hours); and lower for patients undergoing inguinal heria, followed in ascending order by nonschistosomotic patients undergoing splenectomy in schistosomotic patients. PMID- 1517545 TI - "Through a drinking glass and what was found there": pseudocontamination of a hospital's drinking water. AB - OBJECTIVE: Examination of suspended macroscopic debris that was noted in hospital cafeteria drinking water over a prolonged period of time. SETTING: A tertiary care hospital. DESIGN: A retrospective description of events. METHODS: Conventional medical microbiology techniques were employed to determine if contamination of drinking water had occurred. RESULTS: Microscopic examinations of the debris showed live nematodes similar to Strongyloides stercoralis rhabditiform larvae and amoebic trophozoites. A culture of an ice container in the cafeteria yielded coliform bacteria. Hospital employees lost work because of a diarrheal illness thought to be contracted from drinking cafeteria water. Further investigation revealed that the debris contained numerous ciliated organisms, nematodes, fresh water amoebae, bacterial mats, flagellated fungi, and unidentified cysts suggesting that the debris was of a freshwater origin rather than fecal contamination. Another hospital served by a collateral city water line experienced a similar problem. The debris was observed in November when lake water in the reservoir undergoes inversion. CONCLUSIONS: Nonpathogenic freshwater microbiota probably originating from the city reservoir were the cause of pseudocontamination of hospital drinking water. PMID- 1517546 TI - 'Look-back' notifications for HIV/HBV-positive healthcare workers. AIDS Committee of the Society for Hospital Epidemiology of America. PMID- 1517547 TI - Flavimonas oryzihabitans (CDC Group Ve-2). PMID- 1517548 TI - Predisposing factors and antibiotic use in nosocomial infections caused by Xanthomonas maltophilia. PMID- 1517549 TI - Outbreak of pharyngoconjunctival fever at a summer camp--North Carolina, 1991. PMID- 1517550 TI - What is obsessive compulsive disorder? The clinical syndrome and its boundaries. PMID- 1517551 TI - The place of obsessive compulsive disorder in the diagnostic hierarchy. PMID- 1517552 TI - Obsessive compulsive disorder and other disorders. PMID- 1517553 TI - Animal models in obsessive compulsive disorder. PMID- 1517554 TI - Neurobiology of obsessive compulsive disorder: a review. PMID- 1517555 TI - The role of serotonin and dopamine in the pathophysiology of obsessive compulsive disorder. PMID- 1517556 TI - Serotonergic probes in obsessive compulsive disorder. PMID- 1517557 TI - The clomipramine challenge test in obsessive compulsive disorder. PMID- 1517558 TI - Serotonin reuptake inhibitors are the treatment of choice in obsessive compulsive disorder. PMID- 1517559 TI - Role of protein kinase activation in the induction of B cell adhesion by MHC class II ligands. AB - Engagement of MHC class II (Ia) molecules on B cells induces tyrosine phosphorylation, phosphoinositide turnover, elevation of intracellular calcium concentrations, and a rise in cAMP levels. However, a role for these biochemical signals in mediating functional responses induced by Ia ligands remains largely undefined. In this study, we utilized the induction of B cell adhesion by Ia ligands to demonstrate a role for signals transduced via Ia molecules in the generation of a functional response. Ia ligands that induced B cell aggregation induced tyrosine phosphorylation, whereas Ia ligands that did not induce B cell aggregation failed to induce any detectable tyrosine phosphorylation. Ia-induced B cell aggregation and tyrosine phosphorylation were inhibited by genistein and by herbimycin A, inhibitors of tyrosine kinases (PTK). Sphingosine and calphostin C, inhibitors of protein kinase C (PKC), also inhibited Ia-induced adhesion whereas HA1004, an inhibitor of cyclic nucleotide-dependent kinases, did not. Ia ligands induced both LFA-1-dependent and LFA-1-independent B cell adhesion. These two pathways of cell adhesion differed in their requirement for activation signals. PKC activation was sufficient for LFA-1-dependent adhesion, whereas LFA 1-independent adhesion required independent phosphorylation events mediated by PKC and by PTK. These results provide functional relevance for biochemical signals transduced via Ia molecules by demonstrating that Ia-induced B cell adhesion is mediated by the activation of PKC and by one or more PTK. PMID- 1517560 TI - The beta 2-microglobulin dissociation rate is an accurate measure of the stability of MHC class I heterotrimers and depends on which peptide is bound. AB - Stable, recombinant, water-soluble complexes of HLA-A2 and HLA-B27 were reconstituted from 125I-labeled beta 2-microglobulin (beta 2m), a synthetic peptide, and HLA H chain fragments expressed as inclusion bodies in the Escherichia coli cytoplasm. Using this system, we were able to show: 1) the t1/2 of beta 2m dissociation from HLA complexes at 37 degrees C varied from approximately 40 h to less than 1 h, depending on the peptide employed for reconstitution. Peptide length and composition were found to be critical factors in determining the beta 2m dissociation rate. Endogenous peptides form complexes that are about as stable as those formed with typical antigenic peptides. 2) Peptide exchange reactions, in which an exogenous peptide replaces the peptide that is already bound by the class I molecule, proceed readily for complexes that have rapid beta 2m dissociation rates. Thus, difficulties in demonstrating peptide binding to complexes that contain endogenous peptides can be attributed to the stability of the endogenous peptide/class I molecule complex. 3) The peptide exchange reaction does not require concomitant beta 2m dissociation. 4) Distal parts of the class I molecule, which are not directly involved in peptide binding or beta 2m binding, have a major impact on the stability of class I molecules. Thus, these studies show that the dissociation rate of beta 2m is an excellent measure of how tightly a given peptide binds to class I MHC molecules, that the ability to bind peptide is tightly coupled to the binding of beta 2m and vice versa, and that regions of the molecule distal from the binding site influence the stability of peptide binding. PMID- 1517561 TI - Heterogeneity in antigen processing by different types of antigen-presenting cells. Effect of cell culture on antigen processing ability. AB - The ability of normal B cells, peritoneal macrophages, and splenic APC to process and present OVA to a panel of T-T hybridomas with different specificities was investigated. In all cases, B cells were less efficient than unfractionated splenocytes in presenting OVA or its peptides. However, when the presentation of native Ag was compared to the presentation of peptides, it was obvious that there were marked differences in the ability of these two APC populations to generate different epitopes from OVA. Leupeptin inhibits the processing of selected epitopes from native OVA differently when it was presented by spleen cells or B cells, suggesting that these two APC populations differ in their protease content. The effect of in vitro culture on the ability of splenic and peritoneal APC to process OVA was also investigated. Native OVA presentation by macrophages and spleen cells was affected by in vitro culture, more for some epitopes than for other epitopes. In contrast, presentation of exogenous peptides by paraformaldehyde-fixed APC was either not affected by previous culturing for 3 days, or very much improved. Altogether, these data demonstrate that different epitopes on the same protein may be independently and differentially processed by B cells and spleen cells. Furthermore, the precise peptides that are produced may vary with the physiologic state of the APC. PMID- 1517562 TI - A conditional secretory mutant in an Ig L chain is caused by replacement of tyrosine/phenylalanine 87 with histidine. AB - The kappa-chain of the myeloma MOPC 21 is an unusual L chain, in that it is not secreted unless complexed with a H chain. This nonsecreted kappa-chain seems to be retained in the endoplasmic reticulum in association with the protein BiP/GRP78, both in myeloma cells and when expressed in COS-1 fibroblasts. By assaying the fate of the MOPC 21 kappa-chain and its mutated derivatives in COS-1 cells, we show that the cause of the nonsecreted phenotype is the presence of histidine in position 87 of the variable domain. When this amino acid is changed back to the tyrosine that usually occupies position 87, secretion of the unassembled kappa-chain is restored. As in B lymphoid cells, co-expression of gamma H chains in COS-1 cells complements the mutation in the L chain, and rescues secretion of the arrested kappa. Thus, the presence of histidine at position 87 creates a conditional L chain secretory mutant: it is not compatible with normal transport of free L chain, but can be rescued in the presence of H chain. PMID- 1517563 TI - The HLA class I gene family includes at least six genes and twelve pseudogenes and gene fragments. AB - We report the characterization of eight HLA class I homologous sequences isolated from cosmid and lambda libraries made from lymphoblastiod cell line 721 DNA. Four of these sequences, each contained within HindIII fragments of 1.7, 2.1, 3.0, and 8.0 kb, have class I homology extending over short intronexon regions. The remaining four are found within 7.5-, 8.0-, 9.0-, and 16.0-kb HindIII fragments, the first having homology to the 5' half of a class I gene whereas the latter three are homologous to the 3' portion of a class I gene. When combined with the characterization of other class I clones, this work brings the total number of HLA class I homologous sequences cloned and characterized to 18. Restriction mapping of cosmid clones showed that some of these sequences are linked to one another and to other class I pseudogenes and genes within 50-kb regions. Reconstruction experiments using the 18 class I genes and pseudogenes were performed that indicated that we had cloned all of the members of the HLA class I gene family detectable using HLA-A2 genomic DNA as probe. An additional 19th member of the class I gene family was identified using an HLA-E cDNA probe. Further Southern analysis with other class I probes indicated the 19 sequences comprise the entire class I gene family in LCL 721. Locus-specific probes were isolated from five of the eight clones and were used in Southern analysis of diverse genomic DNA to examine the polymorphism of the pseudogene sequences, demonstrating that some of them were highly polymorphic and some were missing entirely in certain haplotypes. An additional class I sequence, not contained within the 721 genome, was identified and may be found in association with the HLA-A11-Bw60 haplotype. Sequence comparisons were carried out to examine the evolutionary relationships among the pseudogenes. Hypothetical events in the evolution of the class I region are discussed. PMID- 1517564 TI - Examination of four HLA class I pseudogenes. Common events in the evolution of HLA genes and pseudogenes. AB - The HLA class I gene family in lymphoblastoid cell line 721 has been studied in detail and a number of sequences in addition to the classical genes have been identified. The cloning, characterization, and nucleotide sequences of four sequences, all full length HLA class I pseudogenes, are described in this report. These pseudogenes, contained within 5.4-, 5.9-, 7.0-, and 9.2-kb HindIII fragments, each have the class I exon-intron structure as well as class I homology in their 5' and 3' flanking regions. However, all four sequences have one or more substitutions that perturb the coding region, leaving little doubt that they are in fact pseudogenes. Comparisons among these sequences and the HLA class I genes revealed that their homology with the class I genes is patchwork. Thus, although some regions have diverged, other contiguous intron-exon sequences are highly conserved. Comparisons in the 5' regions indicate that the pseudogene promoters more closely resemble the classical HLA promoters than the nonclassical promoters as none of the unique structural features found in the HLA-E, -F, or -G regulatory regions are present in any of the pseudogene promoters. Further comparisons revealed that at least two putative gene conversion events, similar to those hypothesized to have occurred in the evolution of some HLA genes, may have occurred in the evolution of some of the pseudogenes. These and other hypothetical events in the evolution of the class I gene family are discussed. PMID- 1517565 TI - Genomic structure and strain-specific expression of the natural killer cell receptor NKR-P1. AB - NK cells are able to lyse a variety of virally infected and neoplastic cells in an MHC-unrestricted manner. The cell-surface protein NKR-P1 is thought to play a key role in this process. NKR-P1, initially identified in rat IL-2 activated NK cells, is encoded in the mouse by at least three similar, but not identical, genes. We previously reported the isolation and characterization of three different NKR-P1 cDNA, termed cDNA 2, 34, and 40, from IL-2 activated mouse NK cells. This report describes the structure of the gene encoding NKR-P1 cDNA 2, the smallest of these three cDNA. Gene 2 is composed of six exons spanning approximately 14 kb of genomic DNA. The first exon encodes the N-terminal intracellular domain, and exons 4, 5, and 6 contain the sequences coding for the CRD. This organization is similar to that of other genes that encode C-type animal lectins. The expression of the NKR-P1 genes in A-LAK cells from 13 mouse strains was examined by Northern blot analysis. NKR-P1 expression appears to coincide with that of the NK1.1 Ag. This observation further supports the hypothesis that the NK1.1 Ag is encoded by one of the NKR-P1 genes. Nucleotide sequence analysis of the promoter region of the three NKR-P1 genes in BALB/c and C57BL/6 mice suggests that differences in the level of expression probably do not result from alterations in the upstream regions of these genes, but may be caused by the expression of strain-specific transacting factors. PMID- 1517566 TI - Locus-specific transcriptional control of HLA genes. AB - One remarkable genetic feature of the class I MHC genes is their unparalleled degree of genetic polymorphism and diversity. The polymorphism is reflected by the fact that multiple loci encode class I molecules, and for each locus there are multiple alleles. In the course of investigating the regulation of HLA-A and HLA-B mRNA in human colorectal carcinoma cell lines, we have noticed a noncoordinate expression of the HLA mRNA in some of these cell lines. This observation prompted us to make use of these cell lines to study the locus specific transcriptional regulation of HLA genes. Bandshift and footprint assays revealed at least three distinct and independent DNA-binding factors that bind to the core regulatory element of the HLA-A and HLB-B gene locus. A "novel" DNA binding factor recognizing the CCAAT motif seems to be important for locus specific expression of HLA-A mRNA, whereas a different factor which binds to a Sp1-like sequence is crucial for normal HLA-B mRNA expression. In certain colorectal cancer cell lines, underrepresentation of these locus-specific DNA binding proteins correlates with the locus-specific down-regulation of HLA mRNA. This observation is further supported by experiments which demonstrated that the locus-specific suppression of exogenously introduced TK-chloramphenicol acetyltransferase DNA constructs, containing the "putative" HLA locus-specific DNA core regulatory sequence, is regulated in a locus-specific manner when introduced into these HLA-A- and HLA-B-deficient human colorectal cell lines. PMID- 1517567 TI - IL-7 up-regulates the expression of IL-8 from resting and stimulated human blood monocytes. AB - Blood monocytes are important cellular sources of a vast array of bioactive substances, including regulatory and chemotactic cytokines. The regulation of these cytokines is of critical importance to the expression of acute and chronic inflammatory responses. IL-7, a T and B cell-activating cytokine, has recently been shown to have stimulatory effects on the expression of several monocyte derived proinflammatory cytokines. We now describe the induction of IL-8 mRNA and extracellular protein from human blood monocytes by IL-7. The up-regulation of IL 8 mRNA by IL-7 was not altered by concomitant treatment with cycloheximide, suggesting that the direct stimulatory effects of IL-7 were not dependent upon de novo protein synthesis. In addition, IL-7 significantly potentiated the production of IL-8 from LPS-, TNF-, and IL-1-treated peripheral blood monocytes. Our findings suggest that IL-7 may play a critical role in the modulation of macrophage-derived cytokine expression and may function in vivo as an important proinflammatory cytokine. PMID- 1517568 TI - IFN-gamma and 1,25(OH)2D3 induce on THP-1 cells distinct patterns of cell surface antigen expression, cytokine production, and responsiveness to contact with activated T cells. AB - Differentiation and maturation of monocytes are accompanied by the expression of specific surface glycoproteins, the secretion of cytokines, and the capacity to respond to ligands. These changes may be influenced by interactions with hormones, soluble lymphocytic products, or direct contact with lymphocytes. We have studied two distinct pathways in the differentiation of a human monocytic cell line, THP-1: one being induced by IFN-gamma and the other by 1 alpha,25 dihydroxyvitamin D3 (1,25(OH)2D3). In THP-1 cells, IFN-gamma induces cell surface expression of HLA-DR and CD54 and production of IL-1 beta, TNF-alpha, and IL-6. In contrast, 1,25(OH)2D3 increases cell surface expression of CD11b and CD14, but fails to stimulate cytokine production. Direct contact of THP-1 with stimulated fixed T cells markedly induces IL-1 beta, TNF-alpha, and IL-6 production by THP 1. Production is higher when THP-1 have been previously exposed to 1,25(OH)2D3 as compared to prior exposure to IFN-gamma. mAb raised against certain relevant cell surface glycoproteins on THP-1 were tested for their ability to block the response of THP-1 to T cells. Antibodies to CD11a, CD11b, and CD11c, alone or in combination, only partially blocked IL-1 beta production by THP-1, whereas antibodies to CD54 and CD14 did not. Thus other unknown structures on the THP-1 cells may be involved in the induction of THP-1 cytokine production by T cell contact. PMID- 1517569 TI - Adherence of infected erythrocytes to venular endothelium selects for antigenic variants of Plasmodium falciparum. AB - Erythrocytes (E) infected with asexual forms of malaria parasites exhibit surface antigenic variation. In Plasmodium falciparum infections, the variant Ag is the P. falciparum E membrane protein 1 (PfEMP1). This molecule may also mediate the adherence of infected E to host venular endothelium. We show here that parasite lines selected for increased adherence to endothelial cells have undergone antigenic variation. Three adherent lines selected from the same P. falciparum clone reacted with the same agglutinating antiserum that failed to agglutinate the parental clone. Immunoprecipitation experiments with the agglutinating anti serum demonstrated that the selected lines expressed cross-reactive forms of PfEMP1 that were of higher m.w. and antigenically distinct from PfEMP1 of the parental clone. When one of the adherent lines was cloned in the absence of selection, a range of variant antigenic types emerged with differing cytoadherence phenotypes. These findings show that selection for cytoadherence in vitro favors the emergence of antigenic variants of P. falciparum and suggest that the requirement for cytoadherence in vivo may restrict the range of antigenic variants of P. falciparum in natural infections. PMID- 1517570 TI - Nongranular proteolytic enzymes of rat IL-2-activated natural killer cells. I. Subcellular localization and functional role. AB - Our investigations indicate that a variety of neutral serine proteases exist in highly purified, IL-2-activated rat NK (A-NK) cells. These enzymatic activities are not restricted to only cytolysin-containing granules and are not defined by only the assay of N-alpha-benzyloxycarbonyl-L-lysine thiobenzylesterase activity. These activities, which we term A-NKP 1, A-NKP 2, A-NKP 3, and A-NKP 4, cleave, respectively, the following fluorogenic peptide substrates: Boc-Phe-Ser-Arg-7 amino-4-methylcoumarin (AMC, trypsin-like); Suc-Ala-Ala-Phe AMC (chymotrypsin like); Suc-Gly-Pro-Leu-Gly-Pro AMC (collagenase-like), and Z-Phe-Arg AMC (another trypsin-like enzyme). The proteases A-NKP 1, A-NKP 2, and A-NKP 3 are not cell surface-associated and appear to be cytosolic as defined by isopycnic sucrose density gradient centrifugation. In contrast, A-NKP 4 appears to be located in lysosomes. Treatment of rat A-NK cells with protease inhibitors that inhibit A NKP 2 and A-NKP 3 also substantially inhibit A-NK cell-mediated cytotoxicity against both NK-sensitive and -resistant targets (YAC-1 and P815, respectively). These results indicate that A-NKP2 and A-NKP 3 may play a role in IL-2-activated NK cell-mediated cytotoxicity. A variety of proteolytic enzymes, in addition to granzymes, therefore exist in A-NK cells. Our studies indicate that a prerequisite to a thorough understanding of the role of proteases in killer cell function is the investigation of several classes of enzymes in addition to granzymes contained in lytic granules. PMID- 1517571 TI - In vivo activity of tumor necrosis factor (TNF) mutants. Secretory but not membrane-bound TNF mediates the regression of retrovirally transduced murine tumor. AB - We have previously demonstrated that murine tumor cells transduced with a retrovirus containing the cDNA encoding wild-type human TNF regress in vivo when injected into immunocompetent mice; this regression is T cell mediated. To determine whether membrane-associated or secreted TNF was responsible for tumor regression, we transduced a cloned murine fibrosarcoma 205 F4 with retroviruses encoding modified human TNF genes. The cloned tumor lines of one retroviral transduction expressed only membrane bound 26-kDa TNF. This TNF could not be cleaved or secreted, but was present on the cell surface. A second retrovirus caused the expression of only secretory 17-kDa TNF, as the transmembrane domain of the cDNA was deleted. The TNF produced by tumor cells transduced with either retroviral vector was functional in vitro as direct lysis of the TNF-sensitive target L929 by transduced tumor cells was demonstrated. The TNF present on 26-kDa expressing tumors was membrane bound as supernatants from cultured 17-kDa TNF expressing tumor cells but not 26-kDa TNF expressing tumors mediated the lysis of L929 cells. Both tumors were injected s.c. into syngeneic mice and tumor growth was measured serially. In repeated experiments, 26-kDa TNF expressing tumors grew progressively in all mice. In contrast, 17-kDa TNF expressing tumors grew for 10 days and then regressed with all animals free of tumor at 28 days. Tumor regression was abrogated by in vivo injection of an anti-TNF antibody. Similar results were obtained in a second tumor model, 203 E4. Thus regression of TNF transduced tumors in vivo requires secretion of TNF, as membrane-bound TNF is insufficient to elicit the host response. PMID- 1517572 TI - Diphtheria toxin- and Pseudomonas A toxin-mediated apoptosis. ADP ribosylation of elongation factor-2 is required for DNA fragmentation and cell lysis and synergy with tumor necrosis factor-alpha. AB - We have reported that diphtheria toxin (DTX) mediates target cell lysis and intranucleosomal DNA fragmentation (apoptosis) and also synergizes with TNF alpha. In this paper, we examined which step in the pathway of DTX-mediated inhibition of protein synthesis was important for induction of cytolytic activity and for synergy. Using a DTX-sensitive tumor cell line, we first examined the activity of the mutant CRM 197, which does not catalyze the ADP ribosylation of elongation factor-2 (EF-2). CRM 197 was not cytolytic for target cells and did not mediate intranucleosomal DNA fragmentation of viable cells. The failure of CRM 197 to mediate target cell lysis suggested that the catalytic activity of DTX is prerequisite for target cell lysis. This was corroborated by demonstrating that MeSAdo, which blocks the biosynthesis of diphthamide, inhibited DTX-mediated protein synthesis inhibition and also blocked target cell lysis. Furthermore, the addition of nicotinamide, which competes with NAD+ on the DTX action site of EF 2, also blocked DTX-mediated lysis. These findings suggest that ADP-ribosylation of EF-2 may be a necessary step in the pathway leading to target cell lysis. In contrast to the sensitive line, the SKOV-3 tumor cell line is sensitive to protein synthesis inhibition by DTX but is not susceptible to cytolysis and apoptosis by DTX. Thus, protein synthesis inhibition by DTX is not sufficient to mediate target cell lysis. The synergy in cytotoxicity obtained with the combination of DTX and TNF-alpha was examined in order to determine the pathway mediated by DTX in synergy. Like the direct lysis by DTX, synergy was significantly reduced by MeSAdo and by nicotinamide. Furthermore, synergy was not observed with combination of CRM 197 and TNF-alpha. These results demonstrate that, in synergy, DTX may utilize the same pathway required for its cytolytic activity. Pseudomonas aeruginosa exotoxin shared most the properties shown for DTX. Altogether, these findings demonstrate that DTX-mediated apoptosis is initiated at a step beyond the ADP ribosylation of EF-2. PMID- 1517573 TI - Selective suppressive effects of Trypanosoma cruzi infection on IL-2, c-myc, and c-fos gene expression. AB - Infection with Trypanosoma cruzi is accompanied by a profound suppression of immune responses including the production of IL-2. Previous experiments have confirmed a correlated decrease in IL-2 mRNA levels in lymphoid cells from infected mice. To further define the molecular basis of this regulation, we have examined the production and degradation of mRNA for IL-2 and other T cell activation genes in cells from T. cruzi-infected mice. Spleen cells from C57BL/6J mice infected with the Brazil strain of T. cruzi were analyzed for the kinetic expression of IL-2, IL-2R alpha, c-myc, and c-fos genes in response to Con A and PMA costimulation. Cells from infected mice exhibited a selective reduction of c myc and c-fos mRNA in association with the severe suppression of the IL-2 gene, but a less severe to comparable production of IL-2R alpha mRNA compared with normal spleen cells. The similar patterns of the suppression of c-myc and IL-2 mRNA suggest a common mechanism of down-regulation of these two genes in T. cruzi infection. Actinomycin D treatment was used to demonstrate that decreased steady state levels of IL-2, c-myc, and c-fos mRNA in cells from infected mice were not due to an increased rate of degradation of these mRNA. Cycloheximide treatment enhanced the expression of IL-2, IL-2R alpha, c-myc, and c-fos mRNA in spleen cells from both normal and infected mice. Although a larger percentage of induction was observed in cells from infected mice, the mRNA levels for IL-2, c myc, and c-fos in cells from infected mice were still lower than those of normal cells. Spleen cells from infected mice precultured for 24 to 72 h before the addition of mitogens showed significant enhancement of IL-2 and c-myc gene expression; however, this recovery was inhibited if fixed T. cruzi was present in the preculture medium. These data suggest that the reduction of IL-2 mRNA in infected mice is not the result of an increased degradation of its mRNA but to down-regulation of transcription of the IL-2 gene in T cells from T. cruzi infected mice. Preculture-induced recovery of IL-2 production appears to result from release from this regulation and full expression of the IL-2 gene. PMID- 1517574 TI - A T cell clone directed at the circumsporozoite protein which protects mice against both Plasmodium yoelii and Plasmodium berghei. AB - Clone B is a cytotoxic T cell clone induced by immunization with Plasmodium yoelii sporozoites which recognizes an epitope on both the P. yoelii and Plasmodium berghei circumsporozoite proteins. It is CD8, uses the V beta 8.1 TCR, and is Kd restricted. When adoptively transferred, it protects mice against infection by both species of malaria sporozoites, and this protection is dependent on IFN-gamma. Clone B cells are more broadly reactive and protective than previously described murine T cell clones against malaria. Clone B may be an important model for immune protection against the spectrum of variant parasites in nature. PMID- 1517575 TI - IL-10 induces transcription of the gene for mouse mast cell protease-1, a serine protease preferentially expressed in mucosal mast cells of Trichinella spiralis infected mice. AB - Mouse bone marrow-derived mast cells (BMMC) obtained by culturing progenitor cells with rIL-3 express mouse mast cell protease (MMCP)-5 mRNA but not MMCP-1 mRNA or MMCP-4 mRNA. In terms of mast cell differentiation, these transcripts encode one early-expressed and two late-expressed chymases, respectively. cDNA and cRNA probes were used in RNase protection assays and RNA blot analyses to study the expression of these three homologous protease genes in cultured mast cells and in helminth-infected mice. Intestinal tissue from Trichinella spiralis infected mice, containing high numbers of mucosal mast cells, had abundant amounts of MMCP-1 mRNA but only minimal amounts of the serosal mast cell transcript that encodes MMCP-4. Exposure of mouse BMMC to rIL-10-induced transcription of the MMCP-1 gene but not the MMCP-4 gene, and a cDNA encoding MMCP-1 was obtained from these rIL-10-treated cells. The expression of MMCP-1 mRNA in BMMC depended on the continuous exposure of these cells to rIL-10, and the level of MMCP-1 mRNA (but not MMCP-5 mRNA) was substantially higher in BMMC maintained in rIL-4 and rIL-10 than in rIL-3 and rIL-10 or in rIL-3, rIL-4, and rIL-10. Thus, whereas rIL-3 elicits transcription of early expressed genes in cultured mast cells, it suppresses the transcription of late-expressed genes. These in vitro and in vivo transcription studies also indicate that rIL-10 preferentially induces differentiation of mouse progenitor cells in a mucosal mast cell-specific lineage, and that expression of granule serine protease genes is regulated in a subclass-specific manner in mouse mucosal mast cells and serosal mast cells. PMID- 1517576 TI - Tumor target-derived soluble factor synergizes with IFN-gamma and IL-2 to activate macrophages for tumor necrosis factor and nitric oxide production to mediate cytotoxicity of the same target. AB - Inflammatory mouse peritoneal macrophages were activated by IFN-gamma in synergy with IL-2 or Lipid A to mediate TNF production for autocrine generation of cytotoxic nitric oxide (NO) to kill P815 or L1210 tumor targets. It was determined that for IL-2, but not Lipid A, to effectively trigger activation of IFN-gamma-primed macrophages, the tumor targets must be also present for interaction with effector macrophages to mediate the production of TNF and NO. IFN-gamma- and IL-2-activated macrophages from syngeneic DBA/2 and allogeneic C3H mice had identical MHC-unrestricted requirements for interaction with DBA/2 mouse derived P815 and L1210 targets to mediate production of TNF and NO for tumor cytotoxicity. To further define the mechanistic requirements for macrophage-tumor target interaction, IFN-gamma- and IL-2-activated macrophages were separated from P815 targets in culture by a semipermeable membrane. Under these conditions, both TNF and NO were produced by the macrophage, which indicated that the requirement for tumor target-macrophage interaction may be due to a soluble factor produced by the target rather than to direct physical contact. This was confirmed by experiments in which 24-h cell-free culture fluids, derived from either P815 or L1210 tumor targets, substituted for the intact tumor cells in the stimulation of TNF mRNA synthesis and secretion with NO generation of TNF mRNA synthesis and secretion with NO generation by IFN-gamma- and IL-2-activated C3H or DBA/2 macrophages. The activity in 24-h culture fluids derived from P815 and L1210 tumor targets was tentatively designated as tumor-derived recognition factor(s) (TDRF) since it was produced constitutively by the tumor targets and synergized with IFN-gamma and IL-2 to induce macrophage production of TNF and NO for death of the same targets. A variety of nontransformed human and mouse fibroblasts, mouse spleen lymphocytes, and two adherent mouse fibrosarcomas did not produce detectable TDRF activity, whereas two mouse T lymphomas, EL4 and EL4.IL-2, produced TDRF activity similar to L1210 mouse leukemia and P815 mastocytoma. The C3H/MCA, a TDRF-nonproducing mouse fibrosarcoma, was susceptible to cytotoxicity mediated by macrophages activated by IFN-gamma and Lipid A, but not by IL-2 triggering. Exogenous TDRF derived from L1210 targets reconstituted the cytotoxic activity for C3H/MCA MCA targets mediated by IFN-gamma- and IL-2-activated macrophages accompanied by the production of TNF and cytotoxic NO.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1517577 TI - A threshold level of coupled G-proteins is required to transduce neutrophil responses. AB - Chemoattractant-induced activation of human polymorphonuclear leukocytes involves receptor coupling to guanine nucleotide binding proteins (G-proteins). Treatment of polymorphonuclear leukocytes with pertussis toxin, which ADP-ribosylates neutrophil G-proteins and uncouples G-proteins from receptors, causes a conversion of cells from responders to nonresponders rather than a gradual decrease in the ability of all cells to respond (Omann, G. M., and J. M. Harter. 1991. Cytometry 12:252; Omann, G. M., and M. M. Porasik-Lowes. 1991. J. Immunol. 146:1303). Flow-cytometric methods were used to measure N-formylpeptide-induced cytosolic Ca2+ elevation and actin polymerization over a wide range of ADP ribosylation levels and showed that although the percentage of responding cells varied markedly, the responding cells were stimulated equivalent to controls. The conditions of pertussis toxin (PT) treatment did not interfere with non-G-protein mediated pathways as assessed by measurement of phagocytosis, a complex process involving the cytoskeleton. We tested the explanation that the all-or-none effect may have been due to heterogeneous insertion of the catalytic subunit of PT into the cells such that responders had no ADP-ribosylation and nonresponders were completely ADP-ribosylated. Measurement of the binding of fluorescent N formylpeptides to permeabilized cells, which allows the distinction between completely ribosylated and normal cells, showed that all cells treated with a submaximal concentration of PT had intermediate levels of receptor-coupled G proteins. Thus, partial ADP-ribosylation had occurred in all cells and the all-or none insertion of the catalytic subunit of PT was ruled out. Thus, there is a threshold of coupled G-proteins required to transduce responses. The ability of PT to inhibit N-formylpeptide-induced actin polymerization and cytosolic calcium elevation was compared and showed that both responses have essentially the same threshold of G-proteins required to transduce the responses. Thus, the pathways regulating actin polymerization and calcium elevation appear to be coupled with equal efficiency to the G-proteins. PMID- 1517578 TI - Production of nitric oxide by murine bone marrow cells. Inverse correlation with cellular proliferation. AB - The present studies were designed to assess the ability of primary cultures of bone marrow cells to produce nitric oxide. We found that two inflammatory stimuli, IFN-gamma and LPS, were potent inducers of nitric oxide production by bone marrow cells. In addition, the CSF granulocyte-macrophage (GM)-CSF and IL-3 as well as TNF-alpha, while inactive by themselves, were synergistic with LPS and IFN-gamma in inducing nitric oxide production. Maximal effects were observed with combinations of GM-CSF and LPS. Nitric oxide production by bone marrow cells was found to be dependent on the presence of L-arginine in the culture medium and inhibitable by NG-monomethyl-L-arginine and L-canavanine, two nitric oxide synthase inhibitors. Nitric oxide produced by the cells was also suppressed by TGF-beta 1 and the tumor promoter 12-O-tetradecanoyl-phorbol-13-acetate. Separation of bone marrow cells by density gradient centrifugation and flow cytometry revealed that the granulocyte-containing fraction was largely responsible for nitric oxide production. In additional experiments we found that treatment of bone marrow cells with GM-CSF significantly stimulated bone marrow cell growth. In contrast, the combination of GM-CSF and LPS or IFN-gamma markedly suppressed cellular proliferation. This suppression was completely reversed by treatment of the cells with NG-monomethyl-L-arginine. Taken together, these data demonstrate that various inflammatory stimuli and cytokines induce nitric oxide production by primary cultures of bone marrow cells and that this mediator may play a role in the regulation of bone marrow cell growth and development. PMID- 1517579 TI - Induction of granulomatous experimental autoimmune thyroiditis in mice with in vitro activated effector T cells and anti-IFN-gamma antibody. AB - Experimental autoimmune thyroiditis (EAT) can be induced in mice after the transfer of mouse thyroglobulin (MTg)-sensitized donor spleen cells that have been activated in vitro with MTg. CD4+ T cells are required for the transfer of EAT in this model. Because CD4+ T cells produce various lymphokines, such as IFN gamma, that may be involved in the activation or regulation of the immune response to MTg and the development of EAT, the present study was undertaken to determine whether a neutralizing mAb to IFN-gamma could modulate the induction or expression of EAT. The anti-IFN-gamma mAb XMG-1.2 had no effect on sensitization of donor cells. However, addition of XMG-1.2 mAb during in vitro activation of MTg-primed spleen cells resulted in more severe EAT in recipient mice. The thyroid lesions in recipients of cells cultured with MTg and XMG-1.2 mAb also exhibited granulomatous changes, which differed qualitatively from the predominantly lymphocytic cell infiltrates in recipients of cells cultured with MTg alone. Recipients of MTg-activated spleen cells also developed severe granulomatous EAT when they were given injections of XMG-1.2 mAb. The effects of XMG-1.2 could be neutralized by IFN-gamma. Recipients of cells cultured in the presence of XMG-1.2 mAb had augmented autoantibody responses, although there were no apparent differences in the IgG subclass distribution of the anti-MTg autoantibody responses. These studies suggest that neutralization of endogenous IFN-gamma results in increased activity of cells capable of inducing granulomatous EAT in mice. PMID- 1517580 TI - A human systemic lupus erythematosus-related anti-cardiolipin/single-stranded DNA autoantibody is encoded by a somatically mutated variant of the developmentally restricted 51P1 VH gene. AB - We report the Ig H and L chain V region sequences from the cDNAs encoding a monoclonal human IgG anti-cardiolipin/ssDNA autoantibody (R149) derived from a patient with active SLE. Comparison with the germ-line V-gene repertoire of this patient revealed that R149 likely arose as a consequence of an Ag-driven selection process. The Ag-binding portions of the V regions were characterized by a high number of arginine residues, a property that has been associated with anti dsDNA autoantibodies from lupus-prone mice and patients with SLE. The VH gene encoding autoantibody R149 was a somatically mutated variant of the 51P1 gene segment, which is frequently associated with the restricted fetal B cell repertoire, malignant CD5 B cells, and natural autoantibodies. These data suggest that in SLE patients a common antigenic stimulus may evoke anti-DNA and anti cardiolipin autoantibodies and provide further evidence that a small set of developmentally restricted VH genes can give rise to disease-associated autoantibodies through Ag-selected somatic mutations. PMID- 1517581 TI - Amplified ELISPOT assay for the detection of HIV-specific antibody-secreting cells in subhuman primates. AB - A novel immunoenzyme amplification technique has been evaluated in an ELISPOT assay for the detection of antigen-specific antibody-secreting cells (ASC) in monkeys. In this assay, mononuclear cells containing putative ASC are incubated for a few hours in antigen-coated wells. Following removal of the cells, zones of solid phase bound antibodies secreted by individual ASC are visualized in four consecutive steps. First, a primary biotinylated anti-immunoglobulin (Ig) reagent is added followed by enzyme-labelled avidin. The amplification procedure comprises the addition of biotinylated anti-enzyme antibodies in the third stage, followed by enzyme-conjugated avidin and substrate. When evaluated in a modified ELISPOT assay for the detection of simian B cells secreting antibodies to the envelope glycoprotein gp120 of the human immunodeficiency virus type 1 (HIV-1), this amplification procedure proved to be suitable even when using anti-human Ig antisera as primary antibody reagents. This development should be useful for other ELISPOT assays where species specific anti-Ig reagents are not always available and, most importantly, for enumerating cells producing immunoreactive substances in such minute amounts that they may escape detection by conventional ELISPOT assays. Furthermore, a functional simian HIV-specific ELISPOT assay could prove valuable for assessing the humoral immunogenicity of future candidate vaccines against the acquired immunodeficiency syndrome (AIDS). PMID- 1517582 TI - Influence of collection and separation of blood samples on plasma IL-1, IL-6 and TNF-alpha concentrations. AB - The anticoagulant used for the collection of blood was found to influence in vitro cytokine production in whole blood. Lithium heparin in certain collection tubes was found to contain endotoxin and induced cytokine synthesis in a time dependent manner whereas endotoxin-free lithium heparin did not. No induction of cytokine occurred in the presence of EDTA which was also able to inhibit endotoxin-induced cytokine synthesis. Synthesis or absence of cytokine correlated with the induction of messenger RNA. Investigation of the kinetics of cytokine induction in whole blood revealed that tumour necrosis factor alpha (TNF) was detectable after 2 h of incubation at 37 degrees C and interleukin-1 beta (IL-1 beta) and interleukin-6 (IL-6) after 3 h. In certain samples IL-1 and IL-6 were detectable in plasma separated immediately from blood collected into endotoxin free lithium heparin, presumably reflecting in vivo synthesis, and similar concentrations were detected after 3 h of incubation of whole blood at 37 degrees C. These data indicate that as long as blood is collected into endotoxin-free anticoagulant then cytokine measurements will reflect the in vivo status. PMID- 1517583 TI - A simple and economical strategy for downstream processing of specific antibodies to human transferrin from egg yolk. AB - A rapid and economical procedure for extraction of antibodies from egg yolk is described. Laying hens were immunized with human transferrin and extracts of egg yolk were purified with a procedure based on affinity chromatography. The resulting purified antibodies were evaluated in a nephelometric system for the assay of transferrin in human sera. The results agreed closely with those obtained with a commercially available anti-human transferrin serum from rabbits. PMID- 1517584 TI - Cellular enzyme-linked immunocircle assay. A rapid assay of hybridomas produced against cell surface antigens. AB - A novel method has been developed for the initial screening of hybridomas produced against cell surface antigens. Glutaraldehyde-fixed cells were immobilized as targets on the lid of a 96-well tissue culture plate which had been precoated with poly-L-lysine. Antibody binding was determined by an immunoenzymatic method in an arrangement permitting both macro- and microscopic examination. After optimization with mouse thymus cells using existing rat monoclonal antibodies, new rat-mouse hybridoma cell lines against mouse thymocytes and bone marrow cells were screened. The antibodies could be characterized immediately both by the localization of the immune reaction (surface or intracellular) or as estimated by the frequency of positive cells recognized by the antibody in the sample. PMID- 1517585 TI - The measurement of transforming growth factor type beta (TGF beta) levels produced by peripheral blood mononuclear cells requires the efficient elimination of contaminating platelets. AB - In recent years there has been an increasing interest in measuring the levels of TGF beta produced by peripheral blood mononuclear cells (PBMC), since its abnormal regulation seems to be involved in several pathological states. Platelet contamination, a common feature in PBMC populations isolated by the standard Ficoll-Paque method, would theoretically disturb the measurement of the levels of TGF beta produced by mononuclear cells, since platelets represent an important source of this cytokine. In this study, supernatants of PBMC cultures from healthy subjects, either platelet-contaminated or uncontaminated, were assayed for TGF beta activity in three different bioassays. We report that the presence of platelets led in most cases to an important overestimation of the TGF beta levels produced by MNC in the Swiss-3T3 bioassay and in a PBMC proliferation assay. In contrast, in the Mv1Lu bioassay these levels were significantly underestimated, an effect which we attribute to the presence of other platelet derived growth factors. These results suggest that the elimination of platelets from PBMC cultures is essential if TGF beta production by mononuclear cells is to be studied. PMID- 1517586 TI - Comparison of selected protocols for the generation of IgA isotype monoclonal antibodies against the gut parasite, Eimeria tenella. AB - Investigations into the role of mucosal IgA in the protective immune response to alimentary tract parasites could be facilitated by the production of specific IgA monoclonal antibodies. To this end, we sought to generate IgA hybridomas against sporozoites of the protozoan, Eimeria tenella using different protocols. Of the methods investigated, intra-enteric priming followed by intravenous boosting of germ-free mice, using splenic lymphocytes in fusions, optimised the yield of IgA hybridomas. Using this protocol, 7/27 specific anti-Eimeria hybridoma antibodies isolated were of IgA isotype. When lymphocytes from mesenteric lymph nodes (MLN) were used in fusions more non-specific IgA secretors were produced than when splenic lymphocytes were used, but the yield of specific anti-Eimeria IgA secreting hybridomas was not improved. By all protocols, a total of nine IgA secreting hybridomas were identified of which eight have been cloned for further studies. PMID- 1517587 TI - Specificity of three anti-complement factor 3 monoclonal antibodies. AB - Monoclonal antibodies which recognize specific C3 fragments may be used to distinguish C3 cleavage products bound to organisms. We defined the specificity of three commercially available monoclonal antibodies by Western immunoblot analysis, enzyme-linked immunosorbent assay, and a quantitative flow cytometric technique. Two monoclonal antibodies with specificity for (i) an erythrocyte bound C3d epitope or (ii) an erythrocyte-bound C3c epitope retained their specificity in all assays. However, the third monoclonal antibody with selectivity for erythrocyte-bound C3bi failed to retain specificity for C3bi bound to non-erythrocyte surfaces in each of our assays; binding instead to all C3 fragments containing the C3g domain. We postulate that erythrocyte C3b-binding surface proteins may alter the availability of certain C3b epitopes and influence observed anti-C3 monoclonal antibody specificity. We conclude that the specificity of monoclonal antibodies for C3 fragments should be confirmed with assays which do not employ erythrocytes or other surfaces bearing C3 receptors. Also, our quantitative flow cytometric technique is a potentially valuable tool for the enumeration of particle-bound C3 fragments. PMID- 1517588 TI - Detection of fecal blood by colloidal gold agglutination using an anti-human hemoglobin monoclonal antibody. AB - Monoclonal antibodies to human hemoglobin were produced and a colloidal gold agglutination method has been developed for detection of fecal occult blood. Since hemoglobin is composed of the tetramer, alpha 2 beta 2, a single monoclonal antibody-labeled colloidal gold can agglutinate with hemoglobin. The lowest detectable hemoglobin concentration was 0.5 micrograms/ml. A total of 785 fecal samples were determined using colloidal gold agglutination and compared with latex agglutination. The colloidal gold agglutination detected blood in 75 samples, whereas latex agglutination detected blood in 76 samples, and among them 70 were positive in both methods. Overall agreement between the two methods was 98%. PMID- 1517589 TI - In vivo primary induction of virus-specific CTL by immunization with 9-mer synthetic peptides. AB - A primary cytotoxic T lymphocyte (CTL) response in vivo requires antigen presentation by cytosolic processing and can not in general be obtained by vaccination with soluble proteins. In the present work we have found that vaccination of mice with pre-processed synthetic peptides, corresponding to endogenous 9-mers produced in influenza A virus-infected cells, resulted in strong primary CTL responses. The generated CTL efficiently killed virus-infected target cells with preference for viral strains having the identical amino acid sequences to the peptides used for immunization. The optimal conditions for a primary in vivo CTL response was obtained with 100 micrograms peptide dissolved in incomplete Freund's adjuvant and injected s.c. at the base of tail. Spleen cells which had been primed 7-10 days earlier were restimulated for 5 days in vitro, using an optimal low peptide concentration (0.05 microM) and tested against virus-infected and peptide-treated target cells. The peptide-induced CTL were major histocompatibility complex class I restricted and CD8 positive. PMID- 1517590 TI - Monocyte proliferation in a cytokine-free, serum-free system. AB - The aim of this study was to establish a cytokine-free, serum-free system which would enable the long-term survival and proliferation of human peripheral blood monocytes. Monocytes were isolated from peripheral blood mononuclear cells (PBMC) by adherence to untreated plastic petri dishes and maintained up to 6 weeks in serum-free medium (SFM) consisting of IMEM, insulin, transferrin, sodium selenite and BSA. Maximal cell proliferation occurred during the first 2 weeks of culture and corresponded to the appearance of large numbers of pure, nonadherent culture derived macrophages. Monocyte maturation was characterised by the modulation of specific cell surface antigens. The percentage of cells staining for the transferrin receptor increased with time, whereas the percentages of cells expressing CD11b, CD11c and HLA-DR remained greater than 60% for the 15 days studied. The mean fluorescent intensities (MFI) of all these antibodies increased significantly with time. The only differences found between the adherent and nonadherent cells, using the above antibodies, were with the MFI for CD11b and CD11c. In both cases, the intensity of staining was significantly greater in the adherent cells. Estimation of cytokine production by cells maintained for 5 weeks in SFM found that they constitutively produced large amounts of macrophage colony stimulating factor (M-CSF) in the absence of any exogenous stimuli. These cells were also found to secrete high levels of tumor necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6) during the 1st week and granulocyte macrophage colony stimulating factor (GM-CSF) during the 3rd week. However, the addition of exogenous GM-CSF (5 U/ml, S5) was found to significantly inhibit monocyte proliferation up to 17 days. This is the first report of proliferation associated with long-term survival of culture derived macrophages in a serum-free, cytokine free system. PMID- 1517591 TI - New parental cell lines for generating human hybridomas. AB - In contrast to the success achieved with the production of hybridomas in the mouse system, creating human hybridomas is problematic. The reason is believed to be a lack of suitable malignant human cell lines. The work presented here demonstrates the establishment of three human parent cell lines--two of which are of T cell origin--by installing hypoxanthine guanosine phosphoribosyl transferase (HGPRT) and/or thimidine kinase (TK) deficiencies into the leukemic cell lines REH, 1301 and SKW-3. In order to isolate true hybridomas, selection procedures must guarantee complete death of the enzyme-deficient malignant parent cells. In this respect sublines with a combined HGPRT and TK deficiency proved to be superior to those with only one enzyme deficiency, especially in combination with the newly developed hypoxanthine/aminopterine/thymidine/azaserine (HATA) selection medium. However, selection media should be of low nonspecific toxicity. This was shown to be a particular property of the thymidine-free azaserine/hypoxanthine (AH) selection medium. Preliminary data show an extraordinary ability of one subclone of the hypoxanthine guanosine phosphoribosyl transferase-negative T cell line SKW-3 to generate human T-T hybridomas. They are of a stable, nearly tetraploid karyotype and express new surface antigens, thus providing new possibilities for the investigation of human T lymphocyte function by means of hybridoma technology. PMID- 1517592 TI - An ultrasensitive system to detect IL-4: enzyme-linked immunosorbent assay (ELISA) combined with an avidin-biotin and enzyme amplification system. AB - We established an ultrasensitive interleukin-4 enzyme-linked immunosorbent assay by combining ELISA with an avidin-biotin and enzyme amplification system. The resultant system (AB-EA ELISA) was 250 times more sensitive than conventional ELISA and 2.5 times more sensitive than enhanced ELISA using an enzyme amplification system alone. The ultrasensitive assay was specific to IL-4 alone; there was no cross reaction with other cytokines. Using the ultrasensitive assay, we measured IL-4 synthesis in vitro by unstimulated and stimulated peripheral blood mononuclear cells (PBMC) from patients with allergic rhinitis. PBMC from patients spontaneously produced measurable amounts of IL-4, whereas IL-4 production from PBMC of normal controls, if any, was below detectable levels. Stimulation of the cultures with LPS significantly increased IL-4 production in two of six patient PBMC cultures but in none of the control cultures; stimulation with Con A markedly increased IL-4 production in all patient PBMC cultures but in only two of seven control cultures. These results suggest that the AB-EA ELISA is a useful method to study the mechanism of IL-4 synthesis in type-I allergic diseases. PMID- 1517593 TI - 13C-NMR spectral analysis of the structures of mouse immunoglobulin G1 carrying allotypes a and j. AB - A novel 13C nuclear magnetic resonance (NMR) method is described for the detection of subtle structural differences between mouse immunoglobulins carrying different allotypes. Fc fragments of mouse IgG1 antibodies carrying allotypes a and j have been selectively labeled with [1-13C]methionine. 13C-NMR spectra have shown that the microenvironment around Met-398 is significantly different for the two kinds of allotypes. Peptide mapping and amino acid sequence analyses have revealed that Val-406 of IgG1 carrying allotype a is substituted for Ile in the case of allotype j. X-ray crystallographic data indicate that Met-398 is in close spatial proximity to Val (Ile)-406. We therefore conclude that the 13C-NMR method can provide us with a novel spectroscopic probe for the structural characterization of allotypic markers. PMID- 1517594 TI - Effective method for synthetic peptide immobilization that increases the sensitivity and specificity of ELISA procedures. AB - A procedure is described for the immobilization of synthetic peptide antigens on a plastic solid phase for performing ELISA. The use of a streptavidin biotinylated peptide system for coating microplates with peptide antigen markedly increased both the sensitivity and the specificity compared to a standard ELISA based on synthetic peptides. The procedure was used for the detection of HIV-1 specific antibodies. PMID- 1517595 TI - A statistical model and computer program to estimate association constants for the binding of fluorescent-labelled monoclonal antibodies to cell surface antigens and to interpret shifts in flow cytometry data resulting from alterations in gene expression. AB - Flow cytometry is used to obtain estimates for the distribution of fluorescent ligands bound to cell surface receptors throughout a cell sample. The equipment used provides light scattering parameters and also cell staining data in the form of dot plots and histograms of fluorescence intensities and the frequency of occurrence of particular fluorescence intensities. It is then assumed that fluorescence intensity is proportional to the number of labelled ligands bound to surface receptors. In this paper we present an outline of a statistical theory to account for the stretching and translation of such flow cytometry profiles which occur either as a result of alterations in gene expression, or from changing the sub-saturating concentration of fluorescent-labelled monoclonal antibodies or lectins used to stain the cells. We describe how the theory has been incorporated into two programs CSAFIT (cell surface antigen fit) and MAKCSA (make data to test CSAFIT). The program CSAFIT can be used to estimate two parameters, alpha and beta, by constrained non-linear regression analysis of the flow cytometry profiles. If the shift results from changes in the concentration of a staining agent then the estimates alpha and beta calculated by CSAFIT are functions of the ligand concentration, the ligand type and the cell line characteristics. They quantify the stretch and translation events that are encountered in flow cytometry. So when the parameter estimates alpha and beta are then further analysed as functions of ligand concentration, estimates for the average association constant K for the binding-site/ligand interaction can be obtained. This paper describes details of the development of programs CSAFIT and MAKCSA. We also discuss the distribution of parameter estimates calculated by CSAFIT and the overall performance of CSAFIT as assessed by simulation studies using data generated by MAKCSA. PMID- 1517597 TI - PROBIT: weighted probit regression analysis for estimation of biological activity. AB - PROBIT estimates biologic activity by weighted probit regression analysis and comparison with a known standard. The program is intended to speed up calculation of the concentration of cytokines in large numbers of cell supernatants. Data are input from either sequential or free-form text files created with a spreadsheet or text editor. This allows transfer of data from a beta-counter equipped with a suitable terminal without retyping. Results are displayed and/or printed as relative potency (% of standard) and 50% effective dose (ED50). PMID- 1517596 TI - Immunoglobulin VH usage analysis by fluorescent in situ hybridization and flow cytometry. AB - We have devised a flow cytometry-based fluorescent in situ hybridization assay that permits analysis of gene expression in a large number of single cells. In this technique, fixed and permeabilized cells are incubated with biotinylated single-stranded RNA probes and by means of a fluorescently labelled second-step reagent, the cells are analyzed by flow cytometry. This is a rapid and simple method that allows all of the steps in the procedure to be performed on cells in suspension. Using this approach, we demonstrate here that immunoglobulin heavy chain variable region (VH) gene expression can be analyzed among individual cells using particular VH family-specific probes. This technique has a high degree of accuracy (greater than 97%) in detecting the fraction of cells expressing a specific message in a population and is sensitive enough to detect immunoglobulin message in LPS activated B cells. The technique has been applied successfully to monitor gene expression in homogeneous and heterogeneous populations. It also allows concurrent analysis of cell surface proteins and gene expression through two-color flow cytometry. This method of monitoring gene expression in individual cells may have a number of applications in immunology and cell biology. PMID- 1517598 TI - Calculation of antibody and antigen concentrations from ELISA data using a graphical method. AB - A graphical method for determining the concentration of either the antibody or the antigen from ELISA data is presented in the form of a GWBASIC program. In the program, ELISAEQ, optical densities (OD) obtained from a 96-well ELISA plate can be input either directly by interfacing a microplate reader to the computer or manually. The program uses standard sample data, and selects the semilogarithmic linear range. Over this range, a least-squares method is used to determine the concentrations of interest. In addition, a hyperbolic interpolation formula is derived over the entire range for estimating the antibody or antigen concentration of the unknown samples whose OD is beyond the linear range. PMID- 1517599 TI - A new MTT assay for examining the cytotoxicity of activated macrophages towards the non-adherent P388 leukaemia cell line. PMID- 1517600 TI - A comparison of commercially available adjuvants for use in research. AB - We evaluated an adjuvant, TiterMax, as an alternative to complete Freund's adjuvant (CFA) for producing antisera in animals. TiterMax, consists of a microparticulate stabilized water-in-oil emulsion of a metabolizable oil, squalene, with the adjuvant block copolymer CRL89-41. This paper reports two evaluations of TiterMax versus CFA and other commercially available adjuvants. In the first study, mice were immunized with a hapten, trinitrophenol, conjugated to hen egg albumin (TNP-HEA) in one of several adjuvants: TiterMax, CFA, Adjuvax, Ribi adjuvant system (RAS), Alhydrogel or Lipovant. TiterMax induced higher longer lasting titers with fewer injections than any of the other adjuvants. The magnitude of the response to TNP varied with species and route of immunization. In the second study, CFA, TiterMax, Adjuvax and RAS were compared in rabbits, mice and goats. Animals were immunized with luteinizing hormone-releasing hormone (LHRH) conjugated to BSA in each adjuvant using comparable protocols. TiterMax induced titers against the peptide equivalent to CFA in all three species. The inflammatory responses induced by TiterMax were mild and transient compared with those induced by CFA. These data suggest that TiterMax is an effective alternative to CFA in many situations. PMID- 1517601 TI - Apoptosis in interleukin-3-dependent haemopoietic cells. Quantification by two flow cytometric methods. AB - The murine haemopoietic cell line, BAF3, undergoes apoptosis when the growth factor IL-3 is withdrawn. Two flow cytometric methods for quantifying the apoptotic cells are described. Cell sorting followed by DNA gel electrophoresis, and both light and electron microscopy have been used to identify the apoptotic cells. In the first method the cells are fixed in ethanol, stained with propidium iodide and a DNA histogram recorded. The apoptotic cells give a 'sub-G1' peak. In the second method unfixed cells are incubated with the bis-benzimidazole, Hoechst 33342. The apoptotic cells take up this dye more rapidly. In this latter method, the non-viable cells can also be enumerated by addition of propidium iodide. The value of the method has been demonstrated in a brief study of the effects of a panel of cytokines on growth and apoptosis. PMID- 1517602 TI - Detection of lipopolysaccharide (LPS) and identification of its serotype by an enzyme-linked immunosorbent assay (ELISA) using poly-L-lysine. AB - A new solid-phase enzyme-linked immunosorbent assay (ELISA) was developed for detection of LPS and identification of its serotype with antisera. Since LPS binds poorly to polystyrene microplates, precoating with poly-L-lysine was used before coating LPS on the surface of microplates. The small amount of LPS in complex mixtures (i.e., less than 1 microgram/ml) could be detectable in ELISA. Use of poly-L-lysine with high molecular weight (MW) provided a higher sensitivity than poly-L-lysine with low MW. Precoating with polymyxin B, or poly L-histidine was less effective in the sensitivity than precoating with poly-L lysine, but it was still better than no precoating. The newly developed ELISA technique could be also applied for detection of anti-LPS antibodies in sera or for screening of monoclonal anti-LPS antibody. PMID- 1517603 TI - In vivo immunosorption--a method for the examination of hormone heterogeneity at low plasma concentrations. Application to progastrin and its products. AB - In order to investigate whether antibody desorption followed by chromatography is useful for the study of ligand heterogeneity in plasma, endogenous plasma gastrins were released from immunoglobulins by denaturation of antisera from 11 rabbits immunized against different fragments of human progastrin. The molecular nature of the in vivo immunosorbed plasma gastrins was characterized by gel chromatography monitored by a library of sequence-specific radioimmunoassays before and after enzyme cleavage. Subsequently, the plasma gastrins were compared with tissue gastrins in extracts of rabbit antral mucosa. The results show that carboxyamidated gastrins and their immediate glycine-extended precursors circulate in rabbit plasma. The carboxyamidated gastrins eluted as gastrin-34 and gastrin-17, both in sulfated and non-sulfated form. Correspondingly, glycine extended gastrin-34 and gastrin-17 also occurred in plasma. The results confirm that the plasma of immunized animals contains substantial quantities of the corresponding endogenous ligands bound to specific antibodies. This in vivo immunosorption phenomenon can be used to study the molecular heterogeneity of hormones and their precursors, when they circulate in concentrations which are otherwise too low to permit examination of their molecular nature. PMID- 1517604 TI - An improved and rapid method for the isolation of rat lymph node or spleen T lymphocytes for T cell proliferation assays. AB - To detect and compare the capacity of antigen presenting cells to present antigen in a T cell proliferation assay, it is necessary to obtain a pure population of antigen-primed T cells that gives low background proliferative responses. Therefore in this paper we present a newly developed isolation method of antigen primed T lymphocytes from rat spleen or lymph nodes. This method uses a nylon wool column to deplete most of the adherent cells and B cells, followed by an indirect elimination method with magnetic beads to remove contaminating Ia positive cells. We compared this method with two commonly used isolation methods, namely a 1.5 h adherence step, followed by a nylon wool column and a Sephadex G 10 column and a 1.5 h adherence step followed by a passage through two consecutive columns of Sephadex G-10. The best T cell enrichment (98% OX-19/52 positive cells) was achieved with the newly developed method, in which the contamination of Ia-positive cells, predominantly B cells and dendritic cells (DC), was diminished to less than 2%. The background response of this population was low and differed significantly with the common methods. Antigen-specific T cell responses induced by splenic DC, expressed as stimulation index, gave very specific responses and showed a steep rise with increasing DC concentrations compared to the common methods. Therefore we conclude that we developed an improved, rapid and reproducible method for the isolation of rat spleen or lymph node T lymphocytes suitable for T cell proliferation assays. PMID- 1517605 TI - A simple standardised protocol for the production of monoclonal antibodies against viral and bacterial antigens. AB - A simple standardised protocol for making monoclonal antibodies against a range of human bacteria and viruses is described. The protocol was designed to reduce the number of steps to a minimum. A one step footpad immunisation was followed by the fusion schedule 10-15 days later. A vital step in the technique was the use of the immunised mouse's spleen to provide a feeder layer post fusion. This simplified the protocol and more importantly greatly accelerated the growth of the hybridomas produced. Immunisation, fusion and clonal expansion of specific antibody secreting hybridomas was complete within 5 weeks. The percentage of hybridomas secreting specific antibody ranged from 6% to 28%, the majority of which were of the IgG isotypes. The method was economical in the use of tissue culture medium and simple to perform. PMID- 1517606 TI - A cleavable biotinylating agent and its use in protein electroblots. AB - A direct method for the synthesis of N-biotinyl penicillamine is described. It has been shown to be a convenient biotinylating agent for antibodies which have been previously coupled with SPDP. The biotinylated antibodies can be used to detect antigens on protein electroblots using 125I-labelled streptavidin and radioautography. The biotin and its attached streptavidin and radiolabel can be removed under mild conditions and the blot reprobed with a different antibody using an identical protocol. PMID- 1517608 TI - World Health Day 1992--strategy in a developing country. PMID- 1517607 TI - Determination of IgE antibodies to the benzyl penicilloyl determinant. A comparison between poly-L-lysine and human serum albumin as carriers. AB - The influence of two different carriers, poly-L-lysine (PLL) and human serum albumin (HSA) in the binding of specific IgE antibodies to the benzyl penicilloyl hapten (BPO) was determined in a solid-phase assay. Serum samples from patients with a history of immediate reaction to penicillin and which had shown the presence of IgE antibodies to BPO were used. Benzyl penicilloyl derivatized cellulose discs were prepared using PLL of different molecular weight and HSA as carriers. These were treated with different molar ratios of benzyl penicillin. These reagents were compared for uptake of BPO-specific IgE using a pool of sera in a radioallergosorbent test (RAST) type assay. Two PLL systems and two HSA systems were finally compared using 26 individual sera. RAST values were compared by Kruskal-Wallis and Wilcoxon tests. The relationships between the four different assays were evaluated by determining Pearson correlation coefficients and the concordance by determining intraclass correlation coefficients (ICC). Analysis of means by the Wilcoxon test revealed significant differences (P less than 0.01) only when the different carrier assays were compared. The correlation coefficients between all the assays were significant (P less than 0.0001), but the ICC was low when the different carrier assays were compared. These results indicate that the nature of the carriers studied (PLL and HSA) influences the capacity for binding IgE antibodies in the RAST procedure. The differences observed indicate that one conjugate cannot be substituted for the other in the determination of IgE antibodies to BPO and that BPO-PLL is preferable. PMID- 1517609 TI - Role of family physician in maternal and child health. PMID- 1517610 TI - Inspiratory spirogram in emphysema. AB - Bronchodilator therapy on inspiratory indices has not been documented so far. Reduction in inspiratory airflow resistance following inhalation of bronchodilator giving the most consistent and significant changes in emphysematous patients has been demonstrated in the present study. PMID- 1517611 TI - Jaundice in pregnancy: a clinical study. AB - In a study on jaundice during pregnancy it was observed that the incidence of jaundice in pregnancy was 1 in 429. Majority of the cases were primigravida, 70% of cases were between 20 and 30 years of age, 60% of the patients were unbooked, 25% of cases were with severe degree of jaundice in respect to serum bilirubin level and 70% cases were with anaemia. There were preponderance of cases in 3rd trimester. Majority of the cases (60%) had jaundice-delivery interval of above 4 weeks. Among the causes virus hepatitis was commonest one (80%). Maternal mortality was recorded as 1 in 20 cases and perinatal mortality was 7 in 17 births (41%). PMID- 1517612 TI - Study of circle system without absorber under controlled ventilation with limited fresh gas flow. AB - A biphasic controlled randomised study was conducted to evaluate the differences in fresh gas flow with alterations in different anaesthetic parameters, on 15 adult female patients of American Society of Anesthetists grade I or II, who underwent elective gynaecological operations with identical premedication and anaesthetic technique in which absorber was by-passed. Intermittent positive pressure ventilation was maintained with a tidal volume of 10 ml/kg and fixed respiratory frequency of 16/minute with inspiratory:expiratory ratio of 1:2. N2O (67%) in O2, a non-depolarising muscle relaxant and a narcotic analgesic were used to maintain the anaesthesia, muscle relaxation and analgesia respectively. Phase I and II of the study were characterised by fresh gas flow of 81/minute and 5.61/minute respectively during steady state and data of both phases were collected every 30 seconds for 5 minutes. Arterial blood samples for arterial CO2 and O2 tension studies were taken towards the end of 5-minute period. In phase I a mean fractional concentration of end tidal CO2 of 3.43% +/- 0.42 (p less than 0.01) and a mean arterial tension of CO2 of 24.06 mm of Hg +/- 4.07 were obtained. In phase II mean fractional concentration of end tidal CO2 3.81% +/- 0.39 (p less than 0.01) and mean arterial O2 of 28 mm Hg +/- 2.32 were obtained. Mean arterial blood O2 saturation was above 99% and mean arterial O2 tension was above 160 mmHg in both the phases. The results were statistically significant. PMID- 1517613 TI - Maternal mortality in a subdivisional hospital of eastern Himalayan region. AB - This study was conducted in a subdivisional hospital of eastern Himalayan region among 5,273 pregnant women over a period of 8 years. There were 29 deaths, the maternal mortality rate was 55 per 10,000. Septic abortion was encountered in 4 among them. Direct obstetric cause was responsible in 72.41% of cases and indirect cause in 27.59% cases. Sepsis, both puerperal and postabortal resulted in 24.14% followed by postpartum haemorrhage in 20.69%. Two of these cases were associated with inversion of the uterus. Preeclampsia caused 10.34% and eclampsia 6.9% of the deaths. Among the indirect causes severe anaemia and pulmonary tuberculosis accounted for 10.34% and 6.9% respectively. Infective hepatitis was the cause in 6.9% cases. Only 17% of the cases were booked and the rest were unbooked. Majority of the cases (62.07%) belonged to the age group of 20-30 years. Primigravida constituted 41.38% of the cases. PMID- 1517615 TI - Ultrasonographic diagnosis of haematometrocolpos in patients refusing vaginal examination. PMID- 1517614 TI - Effect of fenfluramine on serum T3, T4 and TSH levels in obesity. AB - A prospective, randomised case-control trial of an anorectic drug, fenfluramine was conducted on 30 patients of simple obesity. The study revealed that the drug was well tolerated, non-toxic and effective in reducing the body weight and normalising the thyroid profile. Reduction in body weight, rise in serum thyroxine (T4) and fall in serum triiodothyronine (T3) was highly significant (p less than 0.01) in drug treated group as compared to controls (p less than 0.05) after 12 weeks of therapy. There was also fall in serum thyroid stimulating hormone (TSH) levels but without any statistical significance. PMID- 1517616 TI - Deafness: an unusual presentation of pyogenic meningitis. PMID- 1517617 TI - Rare types of ectopic pregnancies. PMID- 1517618 TI - Intracranial foetus in foetu. PMID- 1517619 TI - Neuromyotonia. PMID- 1517620 TI - Multiple meningiomas. PMID- 1517621 TI - Ophthalmology: 21st century knocking at door. PMID- 1517622 TI - Myelodysplastic syndromes. PMID- 1517623 TI - Intradermal sensitivity test prior to use of streptokinase in acute myocardial infarction. PMID- 1517624 TI - Preventing HIV infection through sexual contact: the legal aspect. PMID- 1517625 TI - Non-ulcer dyspepsia. PMID- 1517626 TI - The role of the fentanyl series for pain management: novel delivery systems. PMID- 1517627 TI - System functionality and physicochemical model of fentanyl transdermal system. AB - Fentanyl is an opioid traditionally administered by infusion or injection and more recently in a rate-controlled transdermal dosage form. This system is a four layer laminate on a protective liner. A backing layer seals and protects the drug reservoir, the source for continuous delivery of fentanyl. A membrane controls the release rate of fentanyl from the system. An adhesive layer attaches the system to skin and releases an initial loading dose of fentanyl. The rate of fentanyl delivery through skin is determined by the system and the skin at the application site. The release rate from the system is approximated by Fick's first law of diffusion and is controlled by the rate-controlling membrane. A complete simulation model that combines both in vitro release data and the pharmacokinetic model has been developed and used to show the influence of various physiologic and system variables on serum fentanyl concentrations. PMID- 1517628 TI - Transdermal fentanyl: acute analgesic clinical studies. AB - The transdermal therapeutic system (TTS) is a novel technique of drug administration that can mimic long-term continuous intravenous infusions in maintaining stable drug plasma concentrations. Fentanyl, a potent lipid-soluble synthetic opioid, has been incorporated into such a system and has undergone preliminary clinical trials in postoperative patient populations to assess analgesic efficacy and incidence of undesirable side effects (pruritus, nausea and vomiting, urinary retention, respiratory depression). In general, when applied 2 hr preoperatively, a TTS (fentanyl) patch (in different doses) provides moderate-to-good analgesia for a variety of surgical procedures for periods of up to 3 days. Most patients will require small amounts of systemically administered opioids for supplementary analgesia, especially in the first 24 postoperative hr. The incidence of side effects such as nausea and vomiting varies between studies but can be as high as 70%. Clinically significant respiratory depression is rare but was reported in several of the studies. TTS (fentanyl) is a simple and useful technique for the control of postoperative pain. PMID- 1517629 TI - The history and development of the fentanyl series. AB - In the last two decades, opioid analgesics have assumed an important place in general anesthetic practice in the United States. Part of the reason for this has been the introduction of the potent new agonists fentanyl, sufentanil, and alfentanil. Because of problems with morphine-oxygen anesthesia (incomplete amnesia, occasional histamine-related reaction, marked increases in intra- and postoperative respiratory depression), a suitable alternative was sought but not found among existing opioids. A breakthrough came in 1960, when fentanyl was synthesized, laying the foundation for a better understanding of the structure activity relationships of narcotic analgesics and stimulating interest in developing compounds with even greater potency and safety margins. Investigators interested in opioid anesthesia began to study fentanyl in animals and then in humans. Fentanyl (50-100 micrograms/kg) with oxygen (100%) was evaluated as an anesthetic in patients undergoing mitral valve and coronary artery surgery. Changes in cardiovascular dynamics with induction doses ranging from 8 to 30 micrograms/kg consisted of small decreases in heart rate and arterial blood pressure. All other cardiovascular variables studied, including cardiac output, remained unchanged, even with additional doses up to 100 micrograms/kg. It was determined that fentanyl had use as a narcotic anesthetic, despite its potential for cardiovascular depression and stimulation, respiratory depression, muscle rigidity, and, occasionally, incomplete anesthesia. Since the introduction of fentanyl, two other potent synthetic opioids have been introduced into clinical practice--sufentanil and alfentanil. PMID- 1517630 TI - Transdermal fentanyl: long-term analgesic studies. AB - Alternative routes of drug delivery have particular relevance for use in chronic pain. When the pain experience is constant or nearly constant, a continuous infusion of drug is an ideal way to achieve effective pain relief. Early experience with the transdermal application of fentanyl in chronic cancer pain suggests that it is a safe, noninvasive, effective method of managing pain. The first experience with the use of transdermal fentanyl in cancer pain was reported by Miser and colleagues in 5 patients. They demonstrated that steady-state blood concentrations of fentanyl were linearly related to the transdermal fentanyl dose. The terminal elimination half-life was approximately 34 hr. Zech and colleagues studied 13 patients with chronic cancer pain. Pain relief was obtained and was correlated with plasma fentanyl levels. The largest experience so far was reported in 39 patients in a multicenter trial conducted by Simmonds and colleagues. The median fentanyl dose was 100 micrograms/hr (range, 25-525 micrograms/hr). The initial dose of fentanyl from morphine conversion (6:1) was adequate in 50% of patients and titrated upward by 72 hr for the remaining 50%. Patients wore the system for a median of 84 days (range, 5-365 days). Median supplementary daily dose of morphine was 105 mg/day (range, 0-720 mg/day). The system was able to be maintained through a variety of concomitant events. This experience demonstrated the safety and clinical effectiveness of transdermal fentanyl. The transdermal therapeutic system (fentanyl) is a promising advance in achieving noninvasive, continuous drug administration for the management of chronic cancer pain. PMID- 1517631 TI - Transdermal fentanyl: suggested recommendations for clinical use. AB - Transdermal fentanyl offers the advantage of providing continuous administration of a potent opioid in the absence of needles and expensive drug-infusion pumps for the treatment of cancer pain. When transdermal fentanyl is initiated, it may be necessary to change the dose every 24-48 hr until an appropriate dose is titrated to the needs of the patient. This should be done by providing short acting opioids as rescue analgesics for breakthrough pain. Well-accepted principles established for chronic opioid use in cancer pain management should apply to the administration of transdermal fentanyl as well. These include dose titration, the coadministration of adjuvant drugs to counteract opioid side effects and enhance analgesia, and the need to reassess the patient continuously for recurrent tumor and other new sources of pain. Further clinically relevant studies are needed and include 1) the determination of the relative potency of transdermal fentanyl, especially in comparison with oral and parenteral morphine; 2) a prospective study of the side-effect profile of transdermal fentanyl in relationship to oral morphine; and 3) the role of oral transmucosal administration of fentanyl in selection of starting doses of transdermal fentanyl and as a means to provide rescue doses for breakthrough pain. PMID- 1517632 TI - Transdermal fentanyl: clinical trial at the University of Colorado Health Sciences Center. AB - Transdermal fentanyl is a new fentanyl delivery system recently approved by the FDA for use in patients with chronic pain. In an open-label clinical trial, 5 patients with cancer pain were switched to transdermal fentanyl patches. Patients were evaluated with visual analogue scales (VAS) for pain, mood, and pain relief. A Functional Living Index--Cancer and a symptom questionnaire were filled out 2 wk and 4 wk after initiation of transdermal fentanyl patches. After 2 wk of treatment all patients had VAS improvements in pain control. Patients experienced a decrease in constipation, improved appetite, and improved mood. One patient had drowsiness, which limited dose. The improvements in pain control allowed these patients to perform tasks that they had previously not felt well enough to do. PMID- 1517633 TI - Transdermal fentanyl: seeding trial in patients with chronic cancer pain. AB - In this study, 6 patients with pain from advanced cancer were enrolled in a multicenter, open-label seeding trial of transdermal fentanyl. Following equianalgesic dose conversion, transdermal fentanyl patches were applied every 3 days. Mean fentanyl dosage doubled by week 2 and tripled by week 4. Pain control improved in all patients. There were no significant changes in mood, constipation, nausea, sedation, daily activities, or interpersonal relationships from pretrial to posttrial analyses. Following the study period, 5 patients were monitored for a mean total of 55 days with a mean final fentanyl dose of 240 micrograms/hr. As part of a comprehensive cancer pain management program, transdermal fentanyl appears to be safe and effective, and should prove to be a useful addition to currently available opioid analgesics. PMID- 1517634 TI - Transdermal fentanyl for chronic cancer pain: detailed case reports and the influence of confounding factors. AB - Patients were entered into an open label study to evaluate the efficacy of transdermal fentanyl as an analgesic for chronic cancer pain. The clinical course of 3 patients is described as well as an emphasis on the apparent influence of confounding factors, i.e., factors unique to each patient that appeared to affect that individual's analgesic requirements. Our anecdotal clinical experience suggests that transdermal fentanyl is an acceptable, efficacious, and safe means of pharmacologic management for patients with chronic cancer pain. Our results reinforce the concept that cancer pain is a dynamic, multiply determined process and that, as a result, the effects of a single intervention are difficult to analyze. PMID- 1517635 TI - Transdermal fentanyl use in hospice home-care patients with chronic cancer pain. AB - In this study, 11 cancer patients who experienced severe pain were treated with transdermal fentanyl. Of the 11 patients, 7 completed the 4-wk protocol. Of the 4 patients who did not complete the study, 3 died due to disease progression, and 1 was withdrawn by the primary physician. Patients' pain level, mood, and quality of life were evaluated before starting the transdermal fentanyl patch system and again at 2 and 4 wk. Data from the 7 patients who completed the study showed no statistical differences in pain level, mood, or quality of life at any of the three time points. Starting doses ranged from 25 micrograms/hr to 325 micrograms/hr, with increases from 0% to 300%. There were no significant adverse reactions to the medication. The hospice patients chose to continue with the transdermal fentanyl system for pain control after completing the study. PMID- 1517636 TI - Management of cancer pain with transdermal fentanyl: phase IV trial, University of Iowa. AB - A multicenter study was conducted to determine the patient and physician acceptability of transdermal fentanyl in the management of cancer-related pain. In this study, 10 cancer patients at the University of Iowa received transdermal fentanyl after discontinuing their prior opioid analgesic; 7 patients completed questionnaires before and at 2 and 4 wk following transdermal fentanyl application. There was no significant difference in visual analogue scale scores for pain or mood. Verbal pain descriptor scores improved at 2 wk (P less than .05). There was a nonsignificant tendency toward increased depression and nausea; however, patients spent less time thinking about their illness and felt their cancer was less disruptive to their closest friends/relatives. Constipation, appetite, drowsiness, and concentration were not statistically different. Patients reported improved sleep habits at 2 wk (P less than .05) and tended to require less help with eating, dressing, washing, and using the bathroom. All patients completing the study chose to continue transdermal fentanyl for their cancer pain management. In summary, these data demonstrate the analgesic efficacy of the transdermal fentanyl system and suggest that some patients with cancer related pain could benefit from its use. PMID- 1517637 TI - Transdermal fentanyl: clinical pharmacology. AB - The transdermal therapeutic system (TTS) fentanyl has been designed for rate controlled drug delivery. It provides a convenient regimen for the use of a drug previously limited by a short duration of action and a noninvasive parenteral route for a drug that is unsuitable for oral administration. TTS fentanyl has been developed to provide continuous controlled systemic delivery of fentanyl base for 72 hr. It is a rectangular, transparent unit composed of a protective peel strip and four functional layers. The amount of fentanyl released from each system (25 micrograms/hr per 10 cm2) is proportional to the surface area. So far, four patch sizes are available (10-40 cm2). When the system is applied, a fentanyl depot concentrates in the upper skin layers. Fentanyl plasma concentrations are not measurable until 2 hr after application, and it takes 8-16 hr latency until full clinical fentanyl effects are observed. Steady-state serum concentrations are obtained after several sequential 72-hr applications, and these are maintained for as long as a system is applied. Following removal, serum fentanyl concentrations decline gradually and fall about 50% in approximately 16 hr. This prolonged apparent elimination half-life occurs because fentanyl continues to be absorbed from the skin. Transdermal fentanyl transport is essentially the same between the chest, abdomen, and thigh. The skin-permeability constant is about 0.0125 mL/hr/cm2, much lower than the regional blood supply to a chest-skin area. Because of potential permeability variations among individuals, a special rate-controlling membrane in the system provides additional control of drug release.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1517638 TI - Analgesia using vertebral venous plexus (Batson's Plexus) shunting of rectally administered opioids and anesthetics to the central nervous system. PMID- 1517639 TI - Latency as predictor of postsurgical pain intensity and duration. PMID- 1517640 TI - Cognitive failure in patients with terminal cancer: a prospective study. AB - In a prospective open study, 61 consecutive patients with terminal cancer admitted to the hospital underwent cognitive assessment using the Mini-Mental State Questionnaire three times a week between admission and discharge or death. Mini-Mental State Questionnaire score upon admission was 28 +/- 1.5 in patients who were discharged (N = 14), and 25 +/- 3 in patients who died in the hospital (N = 47, P less than 0.01). The forty-seven patients who died in the hospital presented a total of 66 episodes of cognitive failure (CF) that were defined as a score of less than 24 or a drop of greater than 30% in the score on the Mini Mental State Questionnaire. Of these 47 patients, 39 (83%) presented CF an average of 16 days before death. Upon detection of CF, a complete medical examination, laboratory evaluation, computerized tomography of the brain if indicated by abnormal findings on medical examination, and a complete medication review were performed. The cause of CF could not be established in 37 (56%) cases. Drugs, sepsis, and brain metastasis were the most frequently detected causes and were present in 6, 4, and 4 cases, respectively. In addition, 22 episodes (33%) of CF improved (10 episodes spontaneously and 12 episodes as a result of treatment). Our findings suggest that CF is extremely prevalent during the last weeks of life and, consequently, informed consent for therapeutic or research procedures or resuscitation may be impossible to obtain reliably at that stage. PMID- 1517641 TI - A comparison of the Hopkins Pain Rating Instrument with standard visual analogue and verbal descriptor scales in patients with cancer pain. AB - A self-contained, portable, pain rating instrument that provides an immediate result for documentation purposes was developed to improve pain assessment in cancer patients. The Hopkins Pain Rating Instrument (HPRI) is a 5 x 20 cm plastic visual analogue scale (VAS) with a sliding marker that moves within a groove that measures 10 cm. The side facing the patient resembles a traditional VAS while the opposite side is marked in cm to quantify pain intensity. This psychometric study, which employed a descriptive correlational design, evaluated the reliability and validity of the HPRI by comparing it with a traditional VAS and verbal descriptor scale (VDS). Outpatients with and without pain and inpatients with pain rated their major pain site with the three instruments, which were presented in random order. This was followed by a mental status exam and re rating of pain with the same instruments to assess test--retest reliability. Completing the study were 71 patients with a variety of cancers and a mean age of 52.8 years. Of these patients, 68% had pain and 54% were receiving opioid analgesics. The most common pain sites were the back, leg, and epigastric areas. On initial and repeat testing, there were high correlations between the HPRI and the VAS (r = 0.99, P less than 0.0001) and the VDS (r = 0.85, P less than 0.0001). The correlation coefficients for test--retest reliability for the HPRI, VAS, and VDS were 0.97, 0.97, and 0.94 (P less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1517642 TI - Pediatric patient-controlled analgesia with morphine versus meperidine. AB - To assess prospectively any difference in either analgesia or side effect frequency with morphine versus meperidine, 50 patients, ages 8-16 years, were randomly assigned to receive postoperative patient-controlled analgesia (PCA) with either morphine or meperidine. A numerical rating scale pain score was obtained from each patient twice a day, and any nausea, vomiting, pruritus, or urinary retention requiring catheterization was noted. No significant difference in the incidence of side effects was noted between the morphine and meperidine groups; however, pain scores during morphine PCA were significantly less than those during meperidine PCA (P less than 0.001). These results suggest that morphine is the better opioid for pediatric PCA. PMID- 1517643 TI - Phenytoin as a coanalgesic in cancer pain. AB - The efficacy of phenytoin (PHT), buprenorphine (Bu), and Bu+PHT for the relief of cancer pain of various etiologies was evaluated in a randomized, double-blind study of 3 groups, each comprised of 25 patients. Treatment duration was 1 month. PHT (100 mg by mouth twice daily) provided greater than 50% pain relief to 18 patients (72%) and greater than 75% relief to 4 (16%). Bu (0.2 mg sublingually twice daily) gave 21 patients (84%) greater than 50% relief and 15 patients (60%) greater than 75% relief. Of the Bu-treated patients, 8 had major side effects, while none of the PHT-treated patients experienced significant untoward reactions. Combined therapy (PHT, 50 mg PO+Bu 0.1 mg SL twice daily) provided greater than 50% pain relief to 22 patients (88%) and greater than 75% to 18 (72%); only 3 patients experienced a significant side effect. This study suggests that phenytoin has mild-to-moderate pain-relieving properties of its own and can significantly enhance buprenorphine analgesia. By permitting a lower opioid dose, it may reduce the occurrence of opioid-related side effects. PHT's lack of serious side effects, as well as its documented anxiolytic and antidepressant actions, may add to its comparative usefulness. Further clinical trials of PHT as a coanalgesic and/or adjuvant agent in cancer pain are warranted. PMID- 1517644 TI - Clinicians' quick reference guide to postoperative pain management in adults. Pain Management Guideline Panel. Agency for Health Care Policy and Research, US Department of Health and Human Services. AB - The management of pain is an important part of a health professional's role. The challenge for clinicians is to balance pain control with concern for patient safety and side effects of pain treatments. This is the first of two articles that summarize the highlights of the Agency for Health Care Policy and Research's Panel to develop clinical practice guidelines for the management of pain. This first article includes a summary of the methods used to develop the guidelines and the clinical highlights of pain assessment and management in adults. PMID- 1517645 TI - Clinicians' quick reference guide to acute pain management in infants, children, and adolescents: operative and medical procedures. Pain Management Guideline Panel. Agency for Health Care Policy and Research, US Department of Health and Human Services. AB - The management of pain is an important part of a health professional's role. The challenge for clinicians is to balance pain control with concern for patient safety and side effects of pain treatments. This is the second of two articles presenting the clinical highlights of the Agency for Health Care Policy and Research's Panel to develop clinical practice guidelines for pain management. This article presents the clinical highlights related to the assessment and management of pain in infants and children. PMID- 1517646 TI - Reflex sympathetic dystrophy of the knee following arthroscopic surgery: successful treatment with neural blockade utilizing local anesthetics. PMID- 1517647 TI - Treatment of cancer pain in a former opioid abuser: fears of the patient and staff and their influence on care. PMID- 1517648 TI - The use of urinary catheters in terminally ill cancer patients. AB - Recent reports have commented on the need to improve our knowledge and management of urinary problems in terminally ill patients. We conducted a prospective study in 61 consecutive patients admitted to our palliative care unit (PCU), who were assessed for urinary problems, use of urinary catheters, and management of problems associated with the catheters. A total of 74% (45 of 61) of the patients required a catheter before death, with 23 (38%) being admitted to the PCU with a catheter, and 22 patients (36%) requiring a catheter during admission to PCU. We present our findings regarding the duration of catheter use, indications for catheters, type of catheters used, and complications of catheters. The data collected suggest that, although urinary problems and catheter use are common in terminal illness, if strict guidelines are followed there is no demonstrable mortality, and morbidity associated with catheter use is outweighed by patient benefit. PMID- 1517649 TI - Intestinal obstruction in patients with widespread intraabdominal malignancy. AB - The clinical course of 28 patients with surgically documented widespread intraabdominal malignancy who developed intestinal obstruction was reviewed. Of 26 patients, 13 responded to initial conservative management. In the ten patients treated surgically, there was significant morbidity in 80% and a postoperative mortality of 40%. Reobstruction occurred in 11 patients, responded poorly to therapy, and was associated with a short life expectancy. These results support the use of conservative therapy in the management of intestinal obstruction due to widespread intraabdominal malignancy, with emphasis on the palliation of symptoms and maintenance of quality of life. PMID- 1517650 TI - Children's venipuncture pain: influence of technical factors. AB - Several aspects of venipuncture technique were evaluated to assess their relationship to reported pain. Subjects were 514 children aged 5-17 who had venipuncture performed by a technician in a hospital outpatient laboratory. A research assistant timed the duration of venipuncture and then obtained visual analogue pain scores from the children following venipuncture. Blood volume obtained from venipuncture was also measured. The technician who performed the procedure, amount of blood drawn, and time required to complete the venipuncture did not contribute to the prediction of children's pain. Age and anxiety, which were treated as covariates, were significant predictors of pain. The distribution of pain experienced by children was positively skewed and about one-third of children were above the mean pain score. From the results of this study, venipuncture pain can be recommended for the study of issues in children's pain. Further, the findings recommend the development and utilization of interventions to reduce children's venipuncture pain. PMID- 1517651 TI - Opioids: clinical use as anesthetic agents. AB - Opioids (narcotic analgesics) are widely used in the practice of anesthesia for preanesthetic medication, systemic and spinal analgesia, supplementation of general anesthetic agents, and as primary anesthetics. The last use is particularly widespread for major surgical operations, especially those involving patients with cardiovascular disease. The use of opioids in anesthetic doses is based on the absence of cardiac depression by the opioids. As with all anesthetic drugs, the opioids have limitations and side effects, but for the most part, these are easily managed on the basis of knowledge of their pharmacology. The key to their efficient use is careful titration of dose according to the individual patient's responses to the drug as well as to noxious stimulation. Although there is a very wide margin of safety, allowing administration of enormous doses intraoperatively when the patient's ventilation is supported mechanically, the disadvantage of using doses far in excess of the individual patient's need is a prolonged recovery from anesthesia with the risk of postoperative ventilatory depression. Titration of the dose can be facilitated by computer-controlled infusion pumps with the benefit that the recovery time from anesthetic doses can be appropriate for the individual patient and surgical procedure, and postoperative analgesia can be continued by patient-controlled analgesia, which is another example of computer-controlled opioid infusion. Although specific opioid antagonists are available, their use to antagonize residual anesthetic effects is potentially hazardous. PMID- 1517652 TI - Symptomatic benefit of supplemental oxygen in hypoxemic patients with terminal cancer: the use of the N of 1 randomized controlled trial. AB - The symptomatic effects of oxygen on the dyspnea of terminally ill cancer patients have not been clearly established. Therefore, the decision to administer oxygen is frequently made on an individual basis. We report on the use of N of 1 randomized clinical trial to compare the symptomatic benefit of respiratory failure due to terminal ovarian cancer. A 53-yr-old female patient underwent 6 randomized double-blind crossover trials between oxygen 5 L/min delivered by mask and air 5 L/min delivered by mask. Each treatment period lasted 5 min. The mean saturation of oxygen during the baseline period was 84% +/- 3%, versus 84% +/- 4% on air (P,NS) and 94% +/- 4% on oxygen (P less than 0.001). The mean visual analogue scale (VAS) for dyspnea was 77 +/- 4 during the baseline period as compared to 51 +/- 7 after air (P less than 0.001), and 40 +/- 5 after oxygen (P less than 0.001). The patient and the investigator chose oxygen blindly in 5 of 5 cases, air in 0 and 1 case, and no choice was made in 1 and 0 case, respectively. In 4 cases the patient considered the difference between oxygen and air to be of "much importance," and in one case to be of "moderate importance." No significant treatment, period, or interaction between period and treatment was detected for the difference in the VAS. We conclude that oxygen was significantly better than air for symptomatic improvement in this patient. The N of 1 technique is a simple and reliable method for the assessment of individual patients' response to oxygen. PMID- 1517653 TI - Unrecognized constipation in patients with advanced cancer: a recipe for therapeutic disaster. AB - Morphine-induced constipation can lead to therapeutic disasters by several mechanisms. It can be readily prevented by administration of appropriate laxatives, but the importance of this simple intervention is often overlooked. Problems resulting from uncontrolled constipation include not only fecal impaction and spurious diarrhea, but also pseudoobstruction of bowel causing abdominal pain, nausea and vomiting, and serious interference with drug administration and absorption. Cancer pain may also be exacerbated. All of these contribute unnecessarily to morbidity and costs of health care. A case that exemplifies many of these problems is presented and discussed. PMID- 1517654 TI - Custom-made suppositories of methadone for severe cancer pain. PMID- 1517655 TI - Tissue plasminogen activator, plasminogen activator inhibitor, and other parameters of fibrinolysis in the early stages of taurocholate acute pancreatitis in rats. AB - It is well known that fibrinolytic activity in the early stages of acute experimental pancreatitis (AEP) as assessed by euglobulin lysis time (ELT) is depressed. The aim of this study was to evaluate changes in the fibrinolytic system in the early stages of taurocholate AEP in rats. Tissue plasminogen activator (t-PA) activity, plasminogen activator inhibitor 1 (PAI-1) activity, plasminogen, alpha 1 proteinase inhibitor (alpha 1 PI), alpha 2 antiplasmin (alpha 2 AP), antithrombin III (AT III), fibrinogen, and ELT were measured 0.5, 1, 3, and 6 h after the induction of taurocholate AEP in rats, as well as in sham operated animals and the control group, which was not submitted to any operation. T-PA activity decreased significantly after 3 and 6 h of AEP; PAI activity had a time course reverse to t-PA and was parallel to alpha 1 PI activity. ELT was slightly prolonged after 0.5, 1, and 3 h, whereas alpha 2 AP activity and plasminogen levels increased significantly; AT III activity was increased after 1 h in comparison to control group. Sham operation caused nonsignificant changes in fibrinolysis. Increase of PAI activity and decrease of t-PA could be a reasonable explanation for inhibited plasma euglobulin fibrinolytic activity noted in the early period of AEP. PMID- 1517656 TI - Nonparallel patterns of circadian pancreatic and biliary secretions in fasting rats. AB - We compared the circadian patterns of pancreatic and biliary secretions in fasting rats. For this purpose, indwelling plastic catheters were placed in 10 male Wistar rats (300-320 g) for the collection of biliary and pancreatic secretions. After small samples were taken for analysis, pancreatic and biliary secretions were recirculated into the duodenum by an additional connecting system. The rats were adapted to an inverse night-day cycle by artificial light during the night (8 PM-8 AM) and by darkroom housing at daytime (8 AM-8 PM). During a 24-h fasting period, samples of bile (100 microL) and pancreatic juice (20 microL) were taken every hour for determination of the following parameters: pancreatic and biliary flow rate, protein, amylase, lipase, trypsin, and bile acid output. Peak pancreatic flow rate (1.96 +/- 0.05 mL/h.kg) was achieved toward the end of the dark period at 7 PM. A significant increase of pancreatic secretion could be achieved merely by turning the lights off, a significant decrease by turning the lights on. Similar circadian patterns were found for pancreatic protein, amylase, and lipase output with peak secretions at 7 PM. An increase of nearly 5x was found between minimal (15.64 +/- 0.65 mg/h.kg) and maximal (72.43 +/- 2.83 mg/h.kg) pancreatic protein output. The amplitude was highest for amylase; peak amylase output (13740 +/- 832 U/h.kg) was about 18-fold above minimal output (758 +/- 44.3 U/h.kg). Conversely, the peak of trypsin concentration in pancreatic juice (1095 +/- 17.8 U/mL) occurred during the light period when flow rates were lowest.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1517657 TI - Urinary phospholipase A2 excretion in chronic pancreatic diseases. AB - This study was performed to investigate the behavior of phospholipase A2 (PLA2) in serum and urine of patients with chronic pancreatic diseases and to ascertain whether any factors influenced the results. In 30 controls, 45 patients with pancreatic cancer, 54 with chronic pancreatitis, and 64 with extrapancreatic diseases, serum and urinary PLA2, pancreatic isoamylase and RNase, and urinary N acetylglucosaminidase (NAG) were measured. Serum PLA2 levels were higher in patients with chronic pancreatitis than in all the other groups. In our patients, only occasionally was urinary PLA2 elevated, the increase occurring almost exclusively in the presence of an acute inflammatory disease, e.g., relapsed chronic pancreatitis or active inflammatory bowel disease. A correlation was found between serum PLA2 and serum RNase, an indicator of tissue damage, but not between serum PLA2 and pancreatic isoamylase. Urinary PLA2 output was correlated with its renal input and with RNase output. No correlation was found between PLA2 output and pancreatic isoamylase or NAG urinary excretion. In conclusion, (1) the determination of serum PLA2 activity may be an aspecific test of pancreatic disease; (2) PLA2 urinary excretion occasionally increases, especially in the presence of severe phlogosis, which occurs in chronic pancreatitis, in particular during relapse; and (3) irrespective of the tissue origin of urinary PLA2, its increased excretion may be accounted for in part by its increased circulating levels. It is, however, more likely the consequence of a renal tubular dysfunction, which is sometimes found in patients with pancreatic diseases. PMID- 1517658 TI - Effect of SMS 201-995 on exocrine pancreatic secretion in a patient with external pancreatic fistula. AB - The effect of SMS 201-995 on pancreatic exocrine function was studied. The SMS 201-995 was administered to a patient with an artificial external pancreatic fistula following pancreaticoduodenectomy. Variations in pancreatic exocrine function were assessed by determining the volume and components of the fistula fluid during the following periods: 5 d prior to SMS 201-995 administration, for 5 d during actual administration, and for 5 d after it had been discontinued. The SMS 201-995 was administered by subcutaneous injection of 100 micrograms every 12 h for the first 2 d and then 100 micrograms every 6 h for 3 d. This experiment demonstrated that SMS 201-995 has a strong inhibitory effect on pancreatic exocrine function, markedly reducing the amount of fistula fluid and the production of amylase, total protein, and bicarbonate. PMID- 1517659 TI - Urinoma masquerading as pancreatic pseudocyst. AB - In this article, we report on a patient with recurrent pancreatitis who had received multiple celiac plexus injections for control of pain, and then developed a cystic mass adjacent to the body and tail of the pancreas suggestive of a pancreatic pseudocyst. The cystic mass proved to be a urinoma. The distinction between pancreatic pseudocyst and urinoma was made by CT scan with intravenous contrast utilizing delayed films, which demonstrated leakage of contrast into the cystic structure. This is the first report of a urinoma that resembled a pancreatic pseudocyst. PMID- 1517660 TI - Treatment of infected pancreatic necrosis without surgery. A reported case. PMID- 1517662 TI - Redesigning the system. PMID- 1517661 TI - What is human pancreatic proelastase 1? PMID- 1517663 TI - The relationship between extended periods of immobility and decubitus ulcer formation in the acutely spinal cord-injured individual. AB - Several variables may influence the development of decubitus ulcers during the acute treatment phase following spinal cord injury. Three independent variables were studied: level of injury, completeness of injury and length of time immobilized. Of these, length of immobilization exceeding 6 hours was associated with subsequent development of a sacral or occipital decubitus at a statistically significant level (p = .0094). The presence of a complete injury was associated with decubitus formation at a noticeable but statistically insignificant level (p = .0759). Cervical injuries were not associated with an increased rate of decubitus formation. Results suggested that initial treatment of acute spinal cord injuries should include the use of pressure relieving maneuvers or devices as soon as possible, especially in patients with anticipated extensive immobilization. Recognizing that risk of decubitus formation increases with immobilization time, the period of time involved in initial diagnosis and intervention should be kept to a minimum. This is particularly true in patients with complete spinal cord injuries. PMID- 1517664 TI - Multiple sclerosis: will it come between us? Sexual concerns of clients and their partners. AB - Multiple sclerosis (MS), an unpredictable neurologic disease, is sometimes called the crippler of young adults. This crippling effect often involves sexual functioning. Sexuality is an issue that is frequently difficult for clients, their partners and health care providers to discuss. To address this difficulty, a teaching pamphlet entitled, MS ... Will it Come Between Us? was produced. Open communication and creativity are helpful in dealing with problems frequently encountered by clients with MS: fatigue, impotence, decreased vaginal lubrication, bladder and bowel dysfunction. The pamphlet helps clients with these issues as well as the basics of sexuality as a whole. PMID- 1517665 TI - Acoustic neuroma: postoperative vertigo and the mechanisms of compensation. AB - Ninety-five percent of patients with acoustic neuroma experience some degree of vertigo preoperatively, postoperatively or both. Postoperative vertigo is often a debilitating condition that results when the eighth cranial nerve is severed during surgery to resect a tumor growing around the vestibular portion of this nerve. Thus, surgery for acoustic neuroma affects the membranous labyrinth, which is the functional part of the vestibular apparatus and is primarily concerned with equilibrium. Compensation for impaired equilibrium may be by biofeedback in the vestibular pathways, visual control, exercise or drug therapy. Nurses can significantly influence the recovery of acoustic neuroma patients by encouraging and reinforcing exercise and other mechanisms of vestibular compensation. PMID- 1517666 TI - Multidisciplinary approaches to management of acute head injury. AB - The formation of a multidisciplinary head injury team at St. Michael's Hospital has served to improve the quality of care for acutely head-injured patients. The multidisciplinary team follows the patient from the neurosurgical intensive care unit to the early rehabilitation phase. Treatment for the patient and family focuses on physical, cognitive and psychosocial areas. Cooperation of the various medical and paramedical professionals facilitates earlier and more comprehensive treatment for patients and their families, while enhancing research. PMID- 1517667 TI - The effects of lidocaine on intracranial hypertension. AB - In head-injured adults sudden increases in intracranial pressure (ICP) frequently occur in response to noxious stimuli, such as endotracheal suctioning (ETS). Transient increased ICP may have potentially harmful effects upon head-injured patients. One intervention clinicians believe to be efficacious in blunting ICP response to ETS is administration of lidocaine hydrochloride. This article critiques studies that examined effects of lidocaine in attenuating the ICP response to suctioning and similar stimuli. The literature to date, while providing conflicting results, does demonstrate tentative support for the use of lidocaine prior to ETS as a means of attenuating a rise in ICP. Support was found for the intratracheal route of administration. Additionally when intratracheal lidocaine was coupled with muscle relaxants or other anesthetic agents administered at appropriate times prior to suctioning, large rises in ICP may be effectively blunted. PMID- 1517668 TI - Transcranial Doppler: correlation of blood velocity measurement with clinical status in subarachnoid hemorrhage. AB - Subarachnoid hemorrhage affects approximately 30,000 people each year in North America. Up to 50% of patients who survive the initial hemorrhage experience cerebral vasospasm, often resulting in permanent disability or death. Early detection allows interventions which may prevent catastrophic complications. Diagnosing vasospasm has always been dependent on invasive testing and correlation of the clinical picture. Alterations in neurological assessment, including Glasgow Coma Scale score changes, merely reflect poor cerebral perfusion secondary to the vasospasm, and may not be apparent for days. Transcranial Doppler (TCD) ultrasonography is an exciting diagnostic alternative. This noninvasive test may be done daily at the bedside, and may accurately predict impending vasospasm. PMID- 1517669 TI - Early enteral nutrition and length of stay in stroke patients. AB - The effect of early enteral nutrition on length of stay (LOS) in hospitalized surgical patients has been previously documented. In this study, a sample of a large medical population (stroke patients) was examined to determine if early enteral nutrition affected LOS. A retrospective review of the medical records of nonsurgical stroke patients receiving enteral nutrition, discharged between January 1, 1988 and January 31, 1991, was undertaken. Time to initiation of enteral feeding and LOS were recorded. In patients fed within 72 hours of admission (N = 20), LOS was 20.14 (SD 12.87) days. The LOS for patients fed later than 72 hours from the time of admission (N = 32) was 29.76 (SD 20.05) days. The difference between the groups in LOS was statistically significant (p = 0.036). Although further study is warranted, we concluded that early enteral nutrition may be a factor in shortening LOS in stroke patients. PMID- 1517670 TI - Self-efficacy as a predictor of adjustment to multiple sclerosis. AB - The ability of self-efficacy (SE) and outcome expectations (OE) to predict adjustment to multiple sclerosis (MS) was explored. A sample of 62 respondents who had MS was used to test study hypotheses. Self-efficacy expectations predicted 24% of the variance in adjustment to chronic physical illness. Outcome expectations did not significantly add to the predictive power of SE. However, the model containing SE, OE and degree of disability predicted 51% of the variance in adjustment. PMID- 1517672 TI - Methylprednisolone for acute spinal cord injury. AB - Treatment with high-dose intravenous methylprednisolone is safe and may be associated with significant neurologic improvement in acute spinal cord injury patients. Accurate calculation and administration of the prescribed therapy and identification and assessment of complications should be incorporated into the overall standard of care for the acute spinal cord injury patient. PMID- 1517671 TI - Advance directives. AB - Advance directives concerning treatment have been firmly established in our society. Reactions to them, however, are varied, especially when the health care provider possesses a different belief about the care, or non-provision of care, in a particular situation. It is important for the neuroscience nurse to be in touch with thoughts and feelings concerning a patient's treatment choice, and, when necessary, to seek input and support about those concerns. Clearly, if the nurse cannot carry out the patient's wishes, the nurse can use applicable state law provisions supported by the Patient Self-Determination Act, and request not to participate in the care of that patient. If, however, the neuroscience nurse does provide care, ethically and legally it must be done in accordance with the patient's expressed choices. PMID- 1517673 TI - Gonococcal infection, infertility, and population growth: I. Endemic states in behaviourally homogeneous growing populations. AB - Sexually transmitted diseases such as gonorrhoea are a significant cause of infertility in women when the infection is untreated. They have the potential to alter human population growth rates in many developing countries where sexually transmitted diseases are prevalent due to limited public health facilities for diagnosis and treatment. The authors develop a simple model describing the conditions under which such a disease can exist in a growing population in which sexual partners are chosen at random by proportionate mixing. Using the model, the impact that such a disease could have for a range of possible parameters is examined. Then a full parameter set for gonorrhoea in a developing country is estimated. Analysis demonstrates the significant influence gonococcal infection may have in reducing population growth rate in some communities. For example, the simple model predicts that a prevalence of 20% in sexually active adults results in a 50% reduction in the population growth rate. Finally, the authors discuss how potential control initiatives may change the parameter values that determine transmission and alter the demographic impact of gonorrhoea. PMID- 1517674 TI - Gonococcal infection, infertility, and population growth: II. The influence of heterogeneity in sexual behaviour. AB - Heterogeneity in sexual behaviour has an important influence on the transmission dynamics of sexually transmitted diseases (STDs). The authors describe the development of a simple mathematical model, incorporating such heterogeneity, to investigate the demographic impact of gonorrhoea on human population growth in developing countries where the disease is endemic. Earlier predictions, based on a model with homogeneous mixing, are shown to be in good qualitative agreement with the predictions of a more complex mathematical framework in which the population is stratified both by sex and into two subgroups representing low and high sexual activity, defined on the basis of rates of sexual partner change. Analyses also demonstrate that the pattern of mixing (assortative to random) between the sexual activity classes has an important influence on the predicted prevalence of gonococcal infection in a defined community. The more complex model supports earlier conclusions that gonorrhoea, via its impact on fertility, can significantly reduce net population growth rates. PMID- 1517675 TI - Some results for an SEIR epidemic model with density dependence in the death rate. AB - This paper deals with an SEIR epidemic model for an infectious disease where the death rate depends on the number of individuals in the population. It is also assumed that there is an additional death rate suffered by infected individuals. It is found that there are three steady-state values: one where the population is extinct, one where the population maintains itself at a constant level and the disease is extinct, and one where there is a unique equilibrium with disease present. An interesting and unusual feature is that it is possible for this third equilibrium to exist and be locally unstable. Numerical work and simulation show that we can have cycles of disease incidence with increasing amplitude, a constant amplitude, and a decreasing amplitude, depending on the parameter values of the model. PMID- 1517676 TI - Proceedings of the 7th annual meeting for the Orthopaedic Research of the Japanese Orthopaedic Association. August 1992. Abstracts. PMID- 1517677 TI - Heparin-induced thrombocytopenia. PMID- 1517678 TI - Role of metallothionein in human health. PMID- 1517679 TI - Better dead than second. PMID- 1517680 TI - Carbon monoxide production: a tool for assessing antihemolytic therapy. PMID- 1517681 TI - Type I diabetes mellitus: lessons for human autoimmunity. PMID- 1517682 TI - H-ferritin: a regulatory cytokine that down-modulates cell proliferation. PMID- 1517683 TI - Determinants of donor platelet variability when testing for heparin-induced thrombocytopenia. AB - Heparin-induced thrombocytopenia is a common immune-mediated drug reaction that can be complicated by life-threatening arterial thrombosis. The diagnosis can be confirmed by demonstrating heparin-dependent release of radiolabeled serotonin from washed normal platelets in the presence of patient serum. However, certain serum samples from these patients produce 14C-serotonin release from some but not other normal donor platelets. We investigated this problem of donor platelet variability by studying the reactivities of 10 serum samples from patients with heparin-induced thrombocytopenia with platelets from 10 normal donors (100 serum and platelet combinations). We observed a marked variability in reactivity for patient serum and platelets from normal donors; this initially appeared random. However, closer examination indicated that the reactivities varied hierarchically. Because heparin-induced thrombocytopenia is caused by binding of heparin-dependent IgG to platelet Fc receptors, we examined whether platelet Fc receptor number or function explained the variability in platelet reactivity. We observed that platelet Fc receptor function, as measured by platelet release associated with heat-aggregated IgG, was highly correlated with platelet reactivity to heparin-induced thrombocytopenia serum samples. No significant correlation, however, was found between Fc receptor number and platelet response. Reaction of murine monoclonal antibodies that activate human platelets by means of the platelet Fc receptors was not predictive of platelet reactivity to heparin induced thrombocytopenia serum.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1517684 TI - Treatment of Wilson's disease with zinc: X. Intestinal metallothionein induction. AB - Oral zinc therapy is effective in controlling copper balance in patients with Wilson's disease and blocks the intestinal absorption of copper, as demonstrated by uptake of copper 64 and copper balance measurements. In this study, 64Cu uptake measurements were concomitantly carried out with intestinal biopsies to investigate the relationship of reduced copper absorption to the levels of intestinal metallothionein in patients with Wilson's disease at different stages of zinc therapy. A pronounced increase in intestinal metallothionein levels and a sharp drop in 64Cu absorption were found 4 to 5 days after the initiation of zinc treatment. Conversely, metallothionein levels decreased and 64Cu uptake increased on the discontinuation of zinc therapy. The data indicate that 64Cu absorption varies as a function of intestinal metallothionein level. Intestinal metallothionein levels were found to correlate linearly with urinary zinc levels, which reflect body zinc status. These findings support our hypothesis that intestinal metallothionein induction mediates decreased copper absorption observed during zinc therapy. The suppressive effect of zinc on copper absorption appears to have a half-life of about 11 days. PMID- 1517685 TI - Training at moderate altitude: iron status of elite male swimmers. AB - Laboratory evidence of suboptimal iron status is endemic in chronically training athletes, yet the importance of low serum ferritin values to athletic performance is unclear. The purpose of this study was to monitor iron status in nine male elite swimmers during and after a 3-week training camp at 2225 m altitude. Values for hemoglobin, hematocrit, serum iron, serum transferrin, and transferrin saturation were within the normal range and remained unchanged over the 54-day monitoring period. Serum ferritin level was significantly decreased by day 13 and continued to decline over the period at altitude. Significant recovery was observed by day 35, by which the workload and altitude were reduced. Reticulocyte counts were raised above normal values by the fifth day at altitude and remained elevated for the duration of the study, indicating increased erythropoiesis. In contrast, neither ferritin levels nor reticulocyte counts were changed in six of the nine subjects after 1 month's training at 1000 m. Food histories revealed dietary iron intakes two to three times as great as the recommended dietary allowance for iron. The draw on body iron reserves observed in this study over the heavy training period at moderate altitude indicates that adequate iron stores are necessary to provide a reservoir of iron during periods of increased iron utilization or loss. Further work is required to elucidate the sources and endpoints of the observed iron flux. PMID- 1517686 TI - A simple carbon monoxide breath test to estimate erythrocyte turnover. AB - Carbon monoxide is stoichiometrically released when heme is converted to bilirubin. This report describes and validates a novel technique that permits the estimation of heme turnover and red blood cell survival from the carbon monoxide concentration of end-expiratory breath samples. The end-alveolar Pco of a subject was corrected for environmental carbon monoxide exposure with a simple device that equilibrates with atmospheric carbon monoxide at the same rate as does the subject. The resultant value (endogenous Pco) was tested for its ability to predict heme turnover and red blood cell survival. Red cell survival times of 32 healthy subjects, as calculated from the endogenous Pco, averaged 101 +/- 19 days, a value close to the expected 110-day survival time; 13 patients with clinical evidence of shortened red blood cell survival times had measured erythrocyte life spans ranging from 10 to 59 days. The endogenous Pco of each of seven patients increased after red blood cell transfusion, demonstrating that this technique detected the known rapid turnover of a small fraction of transfused cells. A good correlation (r = 0.91) was observed between heme turnover calculated from endogenous Pco and total fecal biliary pigment output. Carbon monoxide measurements reflect red blood cell destruction in both the marrow and the circulation, therefore yielding shorter life spans than did chromium 51 survival studies. This breath test appears to yield a rapid, semiquantitative assessment of heme turnover and red blood cell survival that is not provided by any other presently available technique. This simple, noninvasive carbon monoxide breath test may find widespread use in the evaluation of anemia and jaundice. PMID- 1517687 TI - Discrepancy between circadian rhythms of inulin and creatinine clearance. AB - To elucidate the disparity between circadian rhythmicity of inulin and creatinine clearance, we simultaneously measured inulin and creatinine clearances every 3 hours during 1 day in 14 normal subjects and in 8 patients with nephrotic syndrome. All patients and normal subjects had a circadian rhythm for inulin clearance with a maximum during daytime and a relative amplitude of 21% +/- 2%. For creatinine clearance a rhythm was either absent or reduced in relative amplitude (p less than 0.01). In all subjects the rate of tubular creatinine secretion was higher at minimum of inulin clearance (night) than at maximum (day). The fractional clearance (relative to inulin) of creatinine was also higher during the night: normal subjects, 1.28 +/- 0.02 versus 1.10 +/- 0.02; patients, 1.78 +/- 0.08 versus 1.45 +/- 0.05 (p less than 0.005). This demonstrates the inaccuracy of creatinine clearance as a measure of glomerular filtration rate (GFR). By subsequent blocking of the tubular secretion of creatinine with cimetidine in four normal subjects, creatinine clearance became similar to inulin clearance during day and night. This confirms that high tubular secretion of creatinine during the night counteracts the normal rhythmicity of glomerular filtration of creatinine. As a result, plasma creatinine concentration is nearly constant during a 24-hour period. In conclusion, tubular creatinine secretion has a circadian rhythm with a phase opposite to the rhythm of GFR, thus blunting or causing absence of a circadian rhythm for creatinine clearance. PMID- 1517688 TI - von Willebrand factor antigen, tissue-type plasminogen activator antigen, and risk of death in human immunodeficiency virus 1-related clinical disease: independent prognostic relevance of tissue-type plasminogen activator. AB - Tissue-type plasminogen activator, von Willebrand factor, and plasminogen activator inhibitor type 1 plasma levels were measured at first consultation in 85 consecutive patients infected with human immunodeficiency virus. Patients were assigned to three groups according to clinical status: mild disease group, intermediate group, and acquired immunodeficiency syndrome group. Significant differences were found in von Willebrand factor, tissue-type plasminogen activator, and plasminogen-activator inhibitor type 1 plasma levels among the three groups: severe clinical status was associated with higher von Willebrand factor, tissue-type plasminogen activator, and plasminogen-activator inhibitor type 1 plasma levels. Significant correlations were found among these three parameters, such known biologic prognostic indicators of human immunodeficiency virus infection as IgA, anti-p24 antibodies, p24 antigenemia, CD4+ lymphocytes, beta 2-microglobulin, and the clinical status. The prognostic relevance of plasma von Willebrand factor and tissue-type plasminogen activator levels at the time of entry into the study was then investigated in a cohort of 65 of the 85 patients who had follow-up during a median period of 22 months. The median survival time for all patients was 39 months after the first consultation. A plasma von Willebrand factor level greater than 200% of the control value had a positive predictive value of 86% for determining nonsurvivors; the median survival time for such patients was 9 months after the first consultation. A positive predictive value of 100% in recognizing nonsurvivors was found for tissue-type plasminogen factor plasma levels greater than 20 ng/ml; the median survival time for these patients was 2 months after the first consultation.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1517690 TI - Functional studies on long-term cryopreserved peripheral blood mononuclear cells from patients with lung cancer and from healthy subjects. AB - To determine the functional abilities of long-term cryopreserved peripheral blood mononuclear cells (PBMCs) from patients with lung cancer and from healthy subjects, we assayed the proliferative and plaque-forming cell (PFC) responses of cells from these individuals after the cells had been cryopreserved for up to 31 months. The stability of these cells for B and T cell quantitative assays was also determined by using their respective monoclonal antibodies. The patients' results were compared with those in healthy subjects to ascertain whether the conclusions derived from the assay of cryopreserved cells are consistent with our earlier studies on fresh cells from similar patients. The results show that proliferative and PFC responses of the frozen cells were not significantly affected by further storage, despite an initial, irreversible functional loss in some subsets of T lymphocytes and monocytes during the process of freezing. They also demonstrate that cryopreserved PBMCs from both patients and controls can be successfully utilized for B and T cell quantitative assays. The conclusions derived from the assay of cryopreserved cells are also consistent with our earlier observations on fresh cells from patients with lung cancer; those studies indicated a B cell functional abnormality caused in part by increased suppressor T cell and monocyte activity. PMID- 1517689 TI - Diphosphoryl lipid A protects rats from lethal hyperoxia. AB - Bacterial endotoxin has been shown to protect rats from lethal hyperoxia. The structure of endotoxin contains diphosphoryl lipid A (DPL) as the lipid backbone stripped of protein and polysaccharides. DPL is the component of the endotoxin molecule that has been demonstrated (in previous studies) to be responsible for the immunologic, mitogenic, pyrogenic, and lethal properties of endotoxin. Monophosphoryl lipid A (MPL) is a nonpyrogenic, nontoxic modification of the DPL molecule that retains its immunostimulatory and mitogenic properties. We hypothesized that DPL may be the actual active component of endotoxin that protects rats from lethal hyperoxia. We also hypothesized that the protection from hyperoxia that is afforded by the DPL component may be related to endogenous release of tumor necrosis factor alpha which should allow MPL to also be protective. To test these hypotheses, we performed a series of experiments in which rats were treated with endotoxin, DPL, MPL or vehicle and exposed to room air or hyperoxia. We found that DPL and endotoxin both protected rats from lethal hyperoxia, but MPL alone was not protective. Even though MPL was not protective, DPL and MPL both increased endogenous release of tumor necrosis factor alpha early after injection (peak DPL level, 3619 +/- 1500 pg/ml, peak MPL level, 4038 +/- 500 pg/ml). Protection in both the endotoxin- and DPL-treated animals was associated with increases in lung antioxidant enzyme activities. We concluded that DPL protect rats from hyperoxia but that MPL is not protective in spite of its immunostimulatory and mitogenic effects. PMID- 1517691 TI - Effects of complement activation on platelet-activating factor and eicosanoid synthesis in rat mesangial cells. AB - The effects of in vitro complement activation and of isolated complement components (C3a, C5a, C3b) on the activity of the microsomal enzyme acetyl coenzyme A: 1-0-alkyl-glycero-3-phosphocholine acetyl transferase (AcTr) in cultured mesangial cells and on the synthesis of prostaglandin E2 (PGE2) were assessed. In vitro complement activation induced by the introduction of purified cobra venom factor (CVF) in culture media containing human serum enhanced mesangial cell PGE2 synthesis and had no effect on microsomal AcTr activity. When media containing C6-deficient serum were used, the stimulatory effect of CVF on PGE2 synthesis was abolished. Introduction of CVF in these media enhanced mesangial cell AcTr activity. These effects were partially reversed when the C6 deficient serum was supplemented with C7-deficient serum to allow formation of the C5b-9 complex. Isolated C3a, C5a, and C3b had opposite effects on PGE2 synthesis and on AcTr activity. Specifically, all components enhanced mesangial cell PGE2 synthesis. In contrast, AcTr activity was enhanced by C3a alone; C5a had no effect, whereas C3b had an inhibitory effect. The observations indicate that in response to complement activation and specific anaphylatoxin agonists, mesangial cell eicosanoid synthesis is not coupled with changes in the activity of AcTr and PAF synthesis. PMID- 1517692 TI - Diltiazem treatment of endotoxic shock in suckling rats. AB - Gram-negative sepsis septic shock continues to produce significant mortality and therefore remains a major medical problem. Vasodilators have been studied in the treatment of circulatory shock. However, the effectiveness of calcium channel blockers in the treatment of newborn endotoxic shock has not been well documented. In the present study, diltiazem, a calcium channel blocker, and nitroprusside, a vasodilator, were used for the treatment of endotoxic shock in 10-day-old rats. Mortality rate, hemodynamics, and glucose metabolism were monitored. Diltiazem at a dose of 0.3 mg/kg attenuated the hypotension, bradycardia, hypoglycemia, and lactacidemia in newborn endotoxic shock. Diltiazem treatment resulted in reduced 24-hour mortality. However, 0.6 mg/kg diltiazem enhanced the hypotension, bradycardia, and lactacidemia in endotoxic shock. Nitroprusside blunted the hypoglycemia and decreased the mortality rate among rats with endotoxic shock. Afterload reduction may be responsible for the beneficial effects of 0.3 mg/kg diltiazem and nitroprusside. Diltiazem at a dose of 0.3 mg/kg reduced the lactacidemia of endotoxic shock more than nitroprusside. Therefore the effects of diltiazem may be due not only to afterload reduction but also to inhibition of cellular calcium influx. We conclude that 0.3 mg/kg diltiazem and 1.0 mg/kg nitroprusside are beneficial for the treatment of endotoxic shock in newborn rats. PMID- 1517693 TI - Effect of chronic renal failure on intestinal transport of biotin in the rat. AB - The present study examined the effect of chronic renal failure (RF) on biotin transport in rat intestine. Chronic RF was induced by subjecting rats to right nephrectomy and left two-thirds nephrectomy. Control rats underwent sham operation but without tissue removal and were pair fed. Transport studies were performed 5 to 6 weeks after operation. Chronic RF was found to cause a marked decrease in the maximal velocity (Vmax) of biotin mucosal-to-serosal transport in jejunal everted sacs with minimal change in the apparent Michaelis-Menten constant (Km) of the transport process. This impairment in biotin transport was found to involve the transport process of the vitamin across the brush border membrane (BBM) domain of the enterocyte as shown by studies with BBM vesicles (BBMVs). These studies with BBMV similarly showed a decrease in the Vmax of biotin transport with minimal change in the apparent Km. The impairment of biotin transport in intestinal BBMVs was not due to dissipation of the Na+ gradient across the BBM (which is the driving force of biotin movement across this membrane) because transport of sodium 22 was found to be similar in BBMVs prepared from the RF rats and the sham-operated PF control rats. These results demonstrate that chronic RF in rats causes impairment in biotin intestinal transport. This impairment is due to a decrease in the number (and/or activity) of the biotin transport carriers and involves the transport process of biotin at the BBM. PMID- 1517694 TI - Hemodynamic effects of high dietary intakes of sodium or chloride in the Dahl salt-sensitive rat. AB - In the Dahl salt-sensitive (Dahl-S) rat, a high sodium without chloride diet (NaAA) and a chloride without sodium diet ("X"Cl) do not increase arterial pressure to the same extent as a high NaCl diet. To explain these differences, hemodynamic responses to acute volume expansion were compared in conscious Dahl-S and Dahl salt-resistant (Dahl-R) rats fed either 7% NaCl, NaAA, or "X"Cl diets for 5 weeks. Before acute volume expansion, on each of the three diets, mean arterial pressures and total peripheral resistances were higher (p less than 0.01) in Dahl-S than in Dahl-R rats, and in Dahl-S, arterial pressure was higher (p less than 0.05 or less) on the 7% NaCl intake than on the other two diets. No group differences were found in cardiac index (thermodilution). Right atrial pressure was also elevated (p less than 0.01) in Dahl-S rats on the 7% NaCl diet. In response to acute volume expansion, arterial pressure did not change, and the decrement of total peripheral resistance was greater in Dahl-S rats than in Dahl R rats on each of the three diets (p less than 0.05 or less). Assuming that reductions of peripheral resistance in response to acute volume expansion reflect withdrawal of sympathetic tone, these results suggest that sympathetic tone is increased comparably on each of the diets in Dahl-S rats. As suggested by the increased right atrial pressure, higher arterial pressure induced by 7% NaCl may be related to an expanded intravascular volume in conjunction with increased neural activity. PMID- 1517695 TI - Lipoproteins and apolipoproteins in human pleural effusions. AB - We investigated the lipoproteins and apoproteins in human serum and pleural effusions of different origin: transudates, inflammatory exudates, and malignant exudates. Transudates had a low cholesterol content of 35 +/- 12 mg/dl (mean +/- SD) because of low levels of low-density lipoprotein (LDL) cholesterol- representing 16% of serum levels--whereas inflammatory exudates (cholesterol 92 +/- 26 mg/dl) and malignant exudates (cholesterol 86 +/- 6 mg/dl) exhibited high levels of LDL, with 67% and 69% of serum levels. Apolipoprotein (apo) B level corresponded with LDL and presented with multiple split-products in sodium dodecyl sulfate-polyacrylamide gel electrophoresis in exudative effusions. LDL levels in effusions correlated with serum levels in exudates but did not correlate with those in transudates. In contrast, lipoprotein(a) appeared in all effusions from patients with detectable serum levels. The isoforms were similar as demonstrated by immunoblotting. Differences were found in the composition of the high-density lipoprotein (HDL) fraction: transudates had cholesterol-rich HDL when compared with serum. HDL particles of malignant exudates were poor in cholesterol, and isoelectric focusing demonstrated more sialized apolipoprotein E. A strongly abnormal HDL level with accumulation of cholesterol was found in a long-standing tuberculous effusion. In conclusion, cholesterol in acute effusions is bound to lipoproteins and derived from the blood. The difference in total cholesterol levels between transudates and exudates is based on the lack of LDL in transudates. Transudates show the lipoprotein characteristics of interstitial fluid. Alterations of lipoproteins occur in chronic inflammation and in malignancy with possible de novo synthesis of apolipoprotein E by tumor cells. Lipoprotein(a) accumulates independently from LDL in the pleural space, a finding that supports the view that the physiologic function of lipoprotein(a) is located in the interstitial space. PMID- 1517696 TI - Pyogenic infections of the spine. PMID- 1517697 TI - Animal rights and experimental medicine. PMID- 1517698 TI - David Ottawa Hancock, MD 1862-1916. PMID- 1517699 TI - Effects of insulin-like growth factor-I (IGF-I) infusion and dietary tri iodothyronine (T3) supplementation on growth, body composition and plasma hormone levels in sex-linked dwarf mutant and normal chickens. AB - This study used a sex-linked dwarf mutant (SLD) chicken to evaluate growth promoting and metabolic effects of recombinant human insulin-like growth factor-I (rhIGF-I) treatment. The SLD chicken is characterized by a 30% reduction in body weight and by high plasma GH levels, low plasma IGF-I and triodothyronine (T3) levels and very low GH binding on liver membranes, suggesting reduced functional GH receptors compared with normal chickens. The effects of a continuous s.c. infusion by osmotic mini-pump of 0.1 mg rhIGF-I/kg per day from 4 to 8 weeks of age on body weight, bone growth and body composition were investigated in female SLD and normal chicks. In addition, half of the birds received a dietary supplement of T3 (0.1 parts per million). Plasma levels of IGF-I, GH, T3, thyroxine and insulin were followed during the treatment. In normal chicks, rhIGF I infusion had no effect on growth and little effect on plasma hormone levels except for a decrease in plasma insulin. In dwarf chicks, rhIGF-I infusion slightly increased body weight but had no effect on longitudinal bone growth. In addition, plasma GH levels were decreased and T3 levels remained lower than in normal chicks. Normal and dwarf chicks showed a decrease in abdominal fat after both IGF-I administration and T3 supplementation, the treatments having additive effects in dwarf chicks only. The combined rhIGF-I and T3 treatment restored a quasi-normal hormonal pattern in dwarf chicks, except for insulin which remained lower than in normal chicks. These results suggest that IGF-I in the chicken has no direct endocrine effect on statural growth. PMID- 1517700 TI - Characterization of inhibin and related proteins in bovine fetal testicular and ovarian extracts: evidence for the presence of inhibin subunit products and FSH suppressing protein. AB - Bovine fetal gonads have been shown previously to contain inhibin bio- and immunoactivity although the ratio of these activities was markedly lower in testicular compared with ovarian extracts throughout gestation. The basis for this difference is examined in this study. Fetal testicular and ovarian high speed supernatant preparations from bovine fetuses aged 180 to 270 days of gestation were sequentially fractionated by dye affinity chromatography, gel permeation chromatography, reversed phase high-performance liquid chromatography and preparative polyacrylamide gel electrophoresis and monitored by inhibin radioimmunoassay and in-vitro bioassay. Three immunoactive fractions were identified in testicular extracts with molecular masses of 30 kDa (Peak I), 43 kDa (Peak IIa) and 29 kDa (Peak IIb). Peak I material only was bioactive. On the basis of these characteristics, Peak I is probably 31 kDa inhibin as previously described, and Peaks IIa and IIb are probably different inhibin alpha subunit precursor fragments. In ovarian extracts, two bio- and immunoactive fractions were identified with molecular masses of 30 kDa (Peak I) and 29 kDa (Peak II). On the basis of size, and biological and immunological activities, the ovarian extract Peak I material is probably bovine 31 kDa inhibin, while the Peak II material is probably a novel inhibin-like protein. FSH-suppressing protein (or follistatin) bio- and immunoactivities were also identified in both testicular and ovarian extracts. It is concluded that the low ratio of inhibin biological/immunological activity in testicular extracts is attributed to the presence of high concentrations of immunoactive alpha subunit precursor fragments which are low to non-detectable in ovarian extracts. These results support our previous hypothesis that, in contrast to the ovary, the inhibin alpha subunit is produced in excess in the fetal testis. PMID- 1517701 TI - Specificity of steroid hormone-induced sex determination in a turtle. AB - The specificity of steroid hormone-induced sex determination was investigated in the red-eared slider, Trachemys scripta, a turtle with temperature-dependent sex determination. All eggs were incubated at either a female-producing temperature (31 degrees C) or a male-producing temperature (26 degrees C) and received control or experimental treatments at stage 17-18 of embryonic development. A variety of treatments induced female sex determination at the male-producing temperature. Oestradiol-17 beta, diethylstilboestrol (DES) (an oestrogen agonist) and norethindrone (NET) (a progestin with reputed oestrogenic as well as anti oestrogenic properties) were the most effective in inducing female sex determination. Other reputed oestrogen antagonists/partial agonists (i.e. tamoxifen, nafoxidine and clomiphene citrate) were also capable of inducing female sex determination, but to a lesser extent. A high dosage of testosterone resulted in the production of some females (7 of 15 hatchlings) whereas dihydrotestosterone had no detectable effect on sex determination. This latter finding suggests that testosterone could be acting via aromatization to oestradiol-17 beta. A few females resulted from eggs that had been treated with aromatase inhibitor, 1,4,6-androstatrien-3,17-dione (ATD) (3 of 97), the antiandrogen hydroxyflutamide (1 of 55) and progesterone (3 of 36), suggesting the possibilities of non-specific effects of these compounds when used in large dosages. Alternatively, metabolites of these compounds may be oestrogenic. Collectively, the results at the male-producing temperature are consistent with the hypothesis that steroid-induced female sex determination is mediated via an oestrogen-specific receptor.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1517702 TI - Opioid modulation of FSH, growth hormone and prolactin secretion in the prepuberal gilt. AB - The role of endogenous opioid peptides (EOP) in modulating GH, prolactin (PRL) and FSH secretion was evaluated in prepuberal (P) gilts. In experiment I, P gilts received 1 (n = 2), 3 (n = 3) or 6 (n = 3) mg naloxone (NAL)/kg body weight i.v. Blood was collected every 15 min for 2 h prior to and 2 h after NAL and an additional 1 h after 100 micrograms gonadotrophin-releasing hormone (GnRH) i.v. In experiment II, P and mature (M) gilts were ovariectomized. Three weeks after ovariectomy, P and M gilts were injected twice a day for 10 days with either 0.85 mg progesterone (P4)/kg body weight or oil vehicle (V), resulting in the following groups: PP4 (n = 11), PV (n = 10), MP4 (n = 11) and MV (n = 10). All gilts received 1 mg NAL/kg body weight on the last day of treatment. Blood samples were collected every 15 min for 4 h before and 2 h after NAL and an additional 1 h after 100 micrograms GnRH i.v. In experiment III, six P and five M gilts were ovariectomized and surgically implanted with intracerebroventricular (i.c.v.) cannulae. Blood was collected every 15 min for 3 h before and 3 h after i.c.v. injection of 500 micrograms morphine in artificial cerebrospinal fluid (CSF) or 250 microliters CSF. In experiment I, all doses of NAL failed to alter PRL secretion, while NAL increased (P less than 0.05) GH secretion in three out of eight gilts. However, NAL suppressed (P less than 0.05) FSH concentrations.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1517703 TI - Cultured dermal papilla cells from androgen-dependent human hair follicles (e.g. beard) contain more androgen receptors than those from non-balding areas of scalp. AB - Androgens stimulate hair growth in many areas, e.g. the beard; they also induce regression and balding on the scalp with increasing age in genetically disposed individuals. The cause(s) of this biological conundrum is unknown but age related; androgen-potentiated changes also occur in the prostate. The mesenchyme derived dermal papilla situated at the base of the hair follicle is thought to play an important role in regulating the growth and development of the follicular epithelium. Since androgens probably act on the hair follicle via the dermal papilla, cultures of dermal papilla cells from human hair follicles with differing responses to androgens in vivo have been established and their ability to bind androgens assessed. Receptor binding was assayed by saturation analysis (0.05-10 nmol/l) using the synthetic non-metabolizable androgen, [3H]mibolerone. Shionogi 115 cells were also assayed as a positive control. Specific high affinity low-capacity androgen receptors were identified in 12 dermal papilla primary cell lines with similar characteristics to established androgen receptors. Cells from androgen-sensitive follicles (beard, scrotum and pubis) contained higher levels of androgen receptors than those derived from relatively androgen-insensitive non-balding scalp follicles whether the receptor content was calculated in relation to cell number, protein or DNA content of the cells. These results support the hypothesis that androgens act on hair follicles via the dermal papilla in vivo and demonstrate that dermal papilla cells exhibit an altered phenotype in culture which depends on the body site from which they were derived.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1517704 TI - Hypophysectomy prevents the castration-induced increase in porphyrin concentrations in the harderian glands of the male golden hamster: a possible role for prolactin. AB - The Harderian glands of golden hamsters contain high concentrations of porphyrin pigments, with female hamsters having considerably higher porphyrin concentrations than males. Castration of male hamsters leads to a rapid increase in porphyrin concentrations; testosterone treatment of females has the opposite effect, suggesting a central role for androgens in inhibiting the realization of high porphyrin concentrations by this organ. Previous studies in our laboratories have shown, however, that administration of a dopamine agonist to castrated hamsters prevents the normal increase in Harderian porphyrins from occurring. This suggests that prolactin is necessary for low androgen levels to lead to maximal increases in Harderian porphyrin concentrations. The present study tested the hypothesis that prolactin is involved in the control of Harderian porphyrin levels in the golden hamster. Although hypophysectomy of male hamsters reduced serum testosterone to levels in castrated hamsters, the resultant increase in Harderian porphyrin concentrations was much less than that seen after a similar period of castration. Furthermore, combining the two procedures (castration and hypophysectomy) also led to a blunted increase in Harderian porphyrin, suggesting that a pituitary hormone is necessary for low testosterone levels to lead to increased porphyrins. Evidence that this pituitary hormone is prolactin comes from the observations that eliminating all pituitary hormones except prolactin, by severing the connection of the pituitary with the hypothalamus or transplanting the pituitary to a distant site (beneath the kidney capsule) led to greatly augmented Harderian porphyrin levels, in intact or castrated male hamsters.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1517706 TI - Effect of administration of growth hormone on plasma and intracellular levels of thyroxine and tri-iodothyronine in thyroidectomized thyroxine-treated rats. AB - We have studied the effects of the administration of GH on plasma levels and peripheral production of tri-iodothyronine (T3) from thyroxine (T4) in thyroidectomized male Wistar rats given a continuous i.v. infusion of T4 (1 microgram/100 g body weight per day) and GH (120 micrograms per day) for 3 weeks. Tracer doses of 131I-labelled T3 and 125I-labelled T4 were added to the infusion. At isotopic equilibrium (10 days after the addition of 125I-labelled T4) the rats were bled and perfused. The plasma appearance rate for T3 was higher (10.6 +/- 1.3 vs 8.4 +/- 2.8 pmol/h per 100 g body weight, P = 0.05) and plasma TSH was lower (246 +/- 24 vs 470 +/- 135 pmol/l, P less than 0.01) in GH-treated rats. The amount of T3 in liver (12.3 +/- 2.8 vs 5.5 +/- 1.7 pmol/g wet weight, P less than 0.01), kidney (11.5 +/- 1.4 vs 6.5 +/- 1.4 pmol/g wet weight, P less than 0.01) and pituitary (8.8 +/- 2.7 vs 4.8 +/- 0.5 pmol/g wet weight, P less than 0.01) was higher than in controls, mainly as a result of an increased local production of T3 from T4, but plasma-derived T3 was also higher in most organs. We found an increased intracellular T3 concentration in the pituitary which may be responsible for the lower plasma TSH concentration in the GH-treated rats. Since the increase in locally produced T3 is found particularly in liver, kidney and pituitary, typical organs that express 5'-deiodinase activity, we suggest that GH acts on thyroid hormone metabolism by stimulating type-I deiodinase activity. PMID- 1517705 TI - Effects of in-vivo administration of insulin-like growth factor-I on the rate of glucose utilization in the soleus muscle of the rat. AB - This study investigated the effects of insulin-like growth factor-I (IGF-I) administered to rats in vivo on the soleus muscle isolated from these rats. In order to study the interactions between IGF-I and insulin, the soleus muscles were incubated in the presence of various concentrations of insulin. IGF-I (190 200 micrograms) was given twice daily; the rats were killed 1 h after one injection of IGF-I (acute administration) or after treatment with IGF-I for 10 days (prolonged administration). The level of IGF-I in plasma was increased by approximately 100% after acute administration and by around 30% after 10 days of treatment with IGF-I. Acute administration of IGF-I to the rats increased the flux of glucose to hexose monophosphate and the rates of lactate formation and glycogen synthesis in the soleus muscles; however, the responsiveness of these muscles to insulin was lost: the increase in the rate of glucose utilization by IGF-I at physiological concentrations of insulin (10 or 100 mU/l) was similar to that observed at maximal concentrations of insulin (1000 mU/l). Similar results were obtained after prolonged treatment of the rats with IGF-I; however, the increase in the rate of glucose utilization was less pronounced than when IGF-I was given acutely and the muscles were still capable of responding to insulin.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1517707 TI - The identification of 125I-labelled iodomelatonin-binding sites in the testes and ovaries of the chicken (Gallus domesticus). AB - The existence of 125I-labelled iodomelatonin-binding sites in chicken ovaries and testes was investigated. The specific binding of 125I-labelled iodomelatonin to chicken ovarian and testicular tissue satisfies all the criteria for a binding site. It was rapid, stable, saturable, reversible, specific and of high affinity. Equilibrium studies showed that total and non-specific binding increased over a range of 5-150 pmol 125I-labelled iodomelatonin/l tested, with specific binding reaching saturation towards the middle range of radioligand concentrations. Scatchard analyses indicated a dissociation constant (Kd) of 36.5 +/- 5.3 pmol/l (means +/- S.E.M.) in the membrane preparations of chicken testes at the middle point in the period of light and a maximum number of binding sites (Bmax) of 0.93 +/- 0.40 fmol/mg protein (n = 6). In membrane preparations of chicken ovaries, the Kd was 102.2 +/- 27.3 pmol/l and the Bmax was 2.77 +/- 0.38 fmol/mg protein (n = 6). Equilibrium and kinetic dissociation constants in the picomolar range indicate high-affinity and physiologically relevant 125I-labelled iodomelatonin binding sites. Competitive inhibition studies determined the following order of relative potency for inhibition of 125I-labelled iodomelatonin-binding to chicken gonadal membranes: 6-chloromelatonin greater than melatonin greater than N acetylserotonin much much greater than 5-hydroxytryptamine, tryptamine, 5 methoxytryptophol, 1-acetylindole-3-acetic acid, 5-hydroxyindole-3-acetic acid and L-tryptophan. The presence of 125I-labelled iodomelatonin-binding sites suggests a direct pineal-gonadal connection in the chicken. PMID- 1517708 TI - N-methyl-D-aspartate does not prevent effects of melatonin on the reproductive and thyroid axes of male Syrian hamsters. AB - The reproductive and thyroid status of male Syrian hamsters maintained on long days (14 h light, 10 h darkness) were assessed after 10 weeks of daily injections of pharmacological doses of melatonin (25 micrograms s.c.) and/or N-methyl-DL aspartic acid (NMDA, 0.025-6 mg i.p.), a compound with receptor sites in the central nervous system which are known to affect reproduction. Melatonin given during the late light phase decreased reproductive organ weights and levels of serum and pituitary prolactin and serum thyroxine (T4); these results are similar to published reports on the effects of chronic short photoperiod treatment of this species. Reproductive organ weights, T4 levels and values for prolactin did not differ significantly between groups receiving only melatonin and those receiving NMDA in addition to melatonin; likewise these variables did not differ significantly between groups receiving only either NMDA or saline. NMDA alone and in combination with melatonin increased serum tri-iodothyronine (T3). The brown adipose tissue enzyme T4 5'-deiodinase demonstrated an increased activity in the presence of NMDA, with the lowest dosage eliciting the most significant effect. Previous studies have demonstrated that NMDA reverses the reproductive effects of short photoperiod. The results of this study show that NMDA is incapable of preventing the inhibitory reproductive effects of exogenously administered melatonin. These observations are consistent with the proposal for a site of action for NMDA on neural regions more proximal than those altered by melatonin; alternatively, NMDA may interfere with neurotransmitter actions in the pathway controlling melatonin production. PMID- 1517710 TI - Pulsatile secretion of LH in the ram: a re-evaluation using a discrete deconvolution analysis. AB - The purpose of the present experiment was to characterize LH secretion pulsatility in rams by analysing the instantaneous secretion rate profile obtained by deconvoluting the plasma concentration profile. Plasma LH concentration profiles were obtained by collecting blood samples every 6 min for 24 h during two different sessions separated by an interval of 15 days. Individual kinetic parameters of ovine LH (oLH) were determined following i.v. injection of oLH. By deconvoluting the plasma concentration profile, it was shown that a pulse has an effective duration of only 20.41 +/- 7.69 (S.D.) min whereas the mean duration estimated from measurement of plasma concentrations was 61.00 +/- 15.16 min. The number of pulses was similar before and after deconvolution (7.80 +/- 1.99 vs 9.70 +/- 3.44 pulses/24 h respectively). Using deconvolution the calculated production rate was 2.26 +/- 0.94 micrograms/kg per 24 h, about 50% of this production being located in the pulses. Statistical analysis of pulsatility revealed that pulse occurrence was a nonperiodic event and that the amplitude of LH pulses and the associated amount of LH released were correlated with the duration of the preceding quiescence period, but had no statistically significant influence on the duration of the following quiescence period. PMID- 1517709 TI - Distribution of the nuclear thyroid-hormone receptor in extraocular and skeletal muscles. AB - The correlation between the occurrence of Graves' ophthalmopathy and Graves' hyperthyroidism may indicate a role for tri-iodothyronine (T3) hormone in the pathogenesis of Graves' ophthalmopathy. In Graves' ophthalmopathy the recti eye muscles are greatly enlarged whereas skeletal muscles seem unaffected. The distribution of the nuclear T3 receptor was studied in normal human and rat eye and skeletal muscles with immunohistochemistry using mouse (monoclonal) antibodies, and by in-situ hybridization for the detection of mRNA encoding the T3-receptor protein. Nuclear staining with T3-receptor antibodies was found in all types of tissues studied. Cytoplasmic staining occurred predominantly in the muscle fibres of the orbital layer of the eye muscles and was generally absent or very low in skeletal muscle fibres and hepatocytes. Immunostaining could be inhibited by preabsorbing the antibodies with bacterially expressed T3-receptor protein, implying specificity. The presence of nuclear and cytoplasmic hormone free T3 receptor sites was indicated after preincubation of sections with T3 hormone; T3-receptor immunostaining decreased and T3-hormone staining increased. In-situ hybridization clearly revealed the presence of alpha-1 and beta-1 forms of the T3-receptor mRNA in liver, skeletal muscles, and orbital and intermediate layers of the eye muscles. The data demonstrate the presence of T3 hormone receptor molecules in the extraocular and skeletal muscles. The different susceptibilities of these muscles to Graves' hyperthyroidism may relate to the quantitative differences in T3 hormone-receptor distribution. PMID- 1517711 TI - Production of parathyroid hormone-related protein by the mammary gland of the goat. AB - Parathyroid hormone-related protein (PTHRP) has been quantified by sensitive specific immunoassays in mammary venous blood and milk from 7 days before to 7 days after parturition in the goat. A significant venous-arterial concentration gradient in plasma PTHRP 1-86 concentrations was demonstrated across the mammary gland, indicating that PTHRP enters the maternal circulation and may have a role in calcium homoeostasis during lactation. Significant and sustained increases in mammary venous and milk PTHRP 1-86 concentrations were found from 1 day before parturition to 7 days afterwards, with peak concentrations of 1.57 +/- 0.58 pmol/l (plasma) and 8.69 +/- 2.95 nmol/l (milk) (mean +/- S.E.M.) occurring on day -1 and the day of parturition respectively. Estimates of the mammary output of PTHRP into plasma in four goats averaged 9% (range 1-25%) of that secreted into milk. Suppression of maternal prolactin concentrations by bromocriptine significantly reduced milk yield and the mammary venous PTHRP concentration, without affecting the concentration of PTHRP in milk. In conclusion, parturition in the goat is associated with a sustained increase in secretion of PTHRP into both plasma and milk; the former may be involved in maternal calcium homoeostasis, whereas the latter may have a role in the neonate. PMID- 1517712 TI - Kinetics of placental lactogen in mid- and late-gestation ovine fetuses. AB - Placental lactogen (PL) is found in fetal plasma throughout gestation, and PL receptors occur on many types of fetal cells. In this study, the entry rate of PL into the fetal circulation was estimated by injection of 125I-labelled ovine PL into two mid- and four late-gestation fetuses. At both ages, PL appears to be distributed into two body pools. One pool has a rapid half-life (approximately 9 min) and a volume of distribution approximately 8% of body weight, while the second pool has a longer half-life (approximately 45 min) and a distribution volume only 4% of body weight. The first pool is presumably blood plasma, but the physiological identity of the second pool is unknown. The effective half-life of PL is approximately 15 min, and the liver is suggested as a probable major site of degradation. These estimates were confirmed in late gestation by measuring fetal plasma concentrations of PL in response to a continuous infusion of unlabelled PL. The kinetic parameters estimated in this study can be used to determine the quantity of exogenous hormone required to alter PL concentration in fetal plasma in a predictable manner. PMID- 1517713 TI - Survival after CPR. PMID- 1517714 TI - Colposcopy. PMID- 1517715 TI - The Norplant contraceptive. PMID- 1517716 TI - The Norplant contraceptive. PMID- 1517717 TI - Secrets, lies, or confidentiality? PMID- 1517718 TI - Cocaine in the ear. PMID- 1517719 TI - Vasectomy procedure. PMID- 1517720 TI - The human genome as metaphor. PMID- 1517721 TI - The relationship between neonatal mortality and hospital level. AB - BACKGROUND: The relative safety of the small obstetrics unit compared with that of the larger or more technologically sophisticated units remains controversial. The purpose of this study was to examine the relationship between neonatal mortality and the level of perinatal services present in the hospital of birth. METHODS: Logistic regression was used to model neonatal mortality as a function of race, weight, and hospital level. Hospitals were classified into five categories using the volume of deliveries and the level of perinatal services available. RESULTS: Both black and white infants born at Level I-A hospitals who weighed less than 2250 (5 lb) fared worse than those born at Level III hospitals. There were no other statistically significant differences between the remaining hospital levels at any weight, although there was a trend toward improved mortality for white babies weighing less than 1500 g (3 lb, 5 oz) born at Level III centers. Level II-B hospitals, which also had neonatal intensive care available, did not demonstrate this trend. RESULTS: The results of this study support the safety of facilities with lower levels of care for delivery of normal birthweight infants and the need for continued centralized delivery of higher levels of care for high-risk patients. PMID- 1517722 TI - The information needs of family physicians: case-specific clinical questions. AB - BACKGROUND: Physicians must be able to rapidly obtain information that answers specific patient-related clinical questions. This study describes the information seeking process in the office practices of family physicians. METHODS: We observed and recorded the information-seeking and information-obtaining behavior of 30 family physicians in their offices. RESULTS: Based on 172 hours of observation and 602 patient visits, family physicians sought answers to an average of only one clinical question for every 15 patients seen. Urban physicians sought answers to more questions than rural physicians (one question for every 9 patients, as compared with one question for every 24 patients; P less than .05). The frequency of seeking information was not related to the physician's age. Busier physicians (those seeing more patients per hour) tended to ask fewer questions (correlation coefficient (r) = -.34, P = .06). Drug prescribing questions were the most common type; second most common were orthopedic questions. Colleagues and the Physicians' Desk Reference were the most often used resources. Eight percent of the questions were not answered. CONCLUSIONS: Among family physicians, patient-related questions are infrequently asked and highly specific. Most questions are rapidly answered using colleagues and books, not journals or computers. PMID- 1517723 TI - Are Papanicolaou smears enough? Acetic acid washes of the cervix as adjunctive therapy: a HARNET study. Harrisburg Area Research Network. AB - BACKGROUND: The Papanicolaou smear has a false-negative rate ranging from 10% to 50%. Adjunctive screening methods for detecting cervical disease are thus of interest. We studied an adjunctive acetic acid wash of the cervix to detect additional cases of cervical disease not found by the Papanicolaou smear. METHODS: All women attending six family practice offices for health maintenance during the period August 1989 through April 1990 were examined (N = 2827). Papanicolaou smears were obtained using a Cytobrush and wooden spatula. Each subject's cervix was also visually examined 1 minute after application of 5% acetic acid. Women with abnormal Papanicolaou smear results or abnormal acetowhite areas on visual inspection of the cervix underwent colposcopy. RESULTS: Ninety-three cases of biopsy-proven condyloma or cervical intraepithelial neoplasia (CIN) were found on the basis of abnormal Papanicolaou smear results alone, 33 on the basis of abnormal acetic acid wash results alone, and 14 on the basis of abnormal results from both a Papanicolaou smear and an acetic acid wash. The prevalence of CIN was 3%. The overall positive predictive value for abnormal results obtained by acetic acid wash was .55 (95% CI = .43 to .63). CONCLUSIONS: Using a 1-minute 5% acetic acid wash improves the detection of cervical disease by 30%. Consideration should be given to augmenting the Papanicolaou smear with this safe, simple, and effective technique on premenopausal women during regular health maintenance examinations. PMID- 1517724 TI - Identifying ABO incompatibility in newborns: selective vs automatic testing. AB - BACKGROUND: Two approaches to identifying blood group (ABO) incompatibility in infants have been suggested. The routine approach is to automatically perform blood type and direct antiglobulin tests on every infant born to a mother with type O blood. The selective approach is to test only significantly jaundiced infants. METHODS: One hundred thirteen infants of mothers with type O blood were tested automatically and 188 other infants were tested selectively. Charts of the infants were reviewed for jaundice recognition and management. RESULTS: Jaundice recognition and management and mean peak bilirubin levels did not differ significantly between the two groups. However, three of the infants who were tested selectively had bilirubin levels above 342 mumol/L (20 mg/dL). Two infants were readmitted for phototherapy despite automatically having had their cord blood tested. All infants requiring phototherapy were clinically jaundiced before 48 hours of age. CONCLUSIONS: Selective cord blood testing was found to be a reasonable, less expensive alternative to routine testing. However, in clinical settings in which newborns are often discharged before the third day of life, automatic cord blood testing may be preferable. All infants discharged before 48 hours of age need close clinical follow-up regardless of the testing protocol used. PMID- 1517725 TI - Primary care research funding sources. AB - BACKGROUND: Numerous studies and anecdotal reports have identified lack of funding as a major obstacle to recruiting young physicians to academic medicine and to developing research in primary care. The focus of this study is the comparison of funding sources reported for published research in the primary care disciplines of family medicine, general internal medicine, pediatrics, and obstetrics and gynecology. METHODS: Articles from a representative sample of the journals of each discipline were eligible for review and inclusion in the study if the work was an original research article. The eligible articles were reviewed and classified by specialty and by funding source. The reported funding sources were categorized into federal, private foundation, local, discipline specific, corporate, and none. After all of the articles had been categorized, 40 articles from each discipline that had not reported any funding source were randomly selected. The primary author of each study was then contacted by telephone for a structured interview to verify the absence of reported funding in the published study. RESULTS: Eligible published articles used in this study numbered 319 in family medicine, 208 in general internal medicine, 522 in obstetrics and gynecology, and 888 in pediatrics. There was a statistical difference between the disciplines regarding the source of funding (chi 2 = 223.0, P less than .0001). Family medicine research was funded primarily by federal and discipline sources. Obstetrics and gynecology research was funded primarily by federal, private foundation, and corporate sources. General internal medicine research and pediatric research were funded primarily by federal and private foundation sources. The majority of the research articles in all four disciplines did not report any funding source. CONCLUSIONS: All four disciplines had diverse sources of funding with many similarities and relatively few differences. An important finding of the study was the amount of unfunded research conducted and published in these primary care disciplines. PMID- 1517726 TI - The effect of patient education on pediatric immunization rates. AB - BACKGROUND: Over the last decade, the immunization rate among preschool children has decreased, especially in the lower socioeconomic population. During this period, reports of outbreaks of immunizable diseases, especially pertussis and measles, have correspondingly increased. This study was designed to evaluate the effect of a brief patient education encounter with new mothers on pediatric immunization rates. METHODS: Two hundred thirty-eight mothers and infants were assigned to an intervention or control group. On the first day postpartum, the mothers in the intervention group participated in a 10- to 15-minute discussion on the importance of immunizations and were given a patient education handout. A reminder letter was mailed to the intervention group at 2 months postpartum. The control group received no special intervention. Infants were followed for their 2 and 4-month immunizations for diphtheria, pertussis, and tetanus and oral polio vaccine (DPT/OPV). At 1 year of age, the infants' immunization records were assessed for the completion of their first three DPT/OPV immunizations. RESULTS: There was no statistically significant difference, by chi-square analysis, in the immunization rates of the control and intervention groups at 2, 4, or 12 months of age. At 1 year of age, 29 of 122 (24%) of the control group had received all three DPT/OPV immunizations, compared with 33 (28%) of 116 infants in the intervention group. CONCLUSIONS: Concordant with similar studies, the immunization rate among infants of parents of lower socioeconomic status (26%) is low. An educational intervention presented to mothers in the postpartum period did not improve the rate of immunization by the age of 12 months. There are undoubtedly several reasons for this failure. Other means to improve immunization rates of infants should be developed and tested. PMID- 1517727 TI - The implications of the Human Genome Project for family practice. AB - The Human Genome Project is an international effort to map and sequence the human genome. The information it will generate has been referred to by some as the "new anatomy," and may play an important role in the future of medicine. However, as with any new technological advancement, the outcome of the Human Genome Project and the subsequent availability of new technology will raise a myriad of ethical, legal, and social concerns. The fear is that this technology will be applied in the clinical setting before the appropriate infrastructure is in place to deal with the issues it will raise. The family physician, far from being merely an interested observer in this process, will be responsible for the delivery of much of this technology as it becomes available. As an intermediary between the technology and the individual patient, the physician has a unique obligation to join in the thoughtful consideration and debate of these issues. PMID- 1517728 TI - ACE inhibitors in congestive heart failure. AB - Despite improved understanding of both disease mechanisms and the quality of care, congestive heart failure (CHF) remains a serious clinical problem. The traditional treatments, diuretics and digitalis, continue to play a major role in the management of many patients with CHF; however, in the last decade, angiotensin-converting enzyme (ACE) inhibitors have been added as an important treatment option. These agents counteract the overstimulation effects of diuretics on the renin-angiotensin-aldosterone system. In addition, some studies indicate that ACE inhibitors may improve symptoms and survival. Recent evidence suggests that in patients with mild to moderate CHF, ACE inhibitor and a diuretic should be administered with or without digitalis to achieve the maximum clinical benefit. PMID- 1517729 TI - Failure to thrive in a ten-year-old girl. AB - A 10-year-old girl was followed over an 18-month period for vague gastrointestinal complaints, failure to thrive, and anemia. She was evaluated by several primary care physicians and consultants who failed to diagnose her problem or alleviate her symptoms. The treatment of an acute illness, a consequence of her presenting problem, resulted in the diagnosis of an unusual entity with important psychological and somatic features. PMID- 1517730 TI - Lanthanide ion luminescence as a probe of DNA structure. 1. Guanine-containing oligomers and nucleotides. AB - Laser-induced Eu(3+) luminescence spectroscopy is used to probe the interaction of Eu(3+) ion with guanine-containing nucleotides and single-stranded oligomers. By using time-resolved and non-time-resolved Eu(3+) luminescence techniques, two classes of Eu(3+) binding site are observed in oligo(dG)10, oligo(dG)8, oligo(dG)6, oligo(dG)4, and d-GMP. One class of site binds Eu(3+) ions more strongly than the other. Since the "tight" class of bound Eu(3+) ions have two coordinated water molecules, it is inferred that six or seven atoms from the oligomers are coordinating the Eu(3+). The "weaker" class of Eu(3+) ion sites involve the coordination of six or seven water molecules and therefore, are coordinated by one or two atoms from the oligomer. The tight class of Eu(3+) binding site is attributed to an interstrand association of Eu(3+) with the oligomers forming dimeric or polymeric structures. The dissociation constants (Kd) for the 1:1 complexes Eu(d-GMP)+ and Eu(d-GTP)- have been determined as well as the Kd for the dimerization reaction of Eu(d-GMP)+. The Tb(3+) luminescence enhancement properties of these molecules are also examined in relation to their EU(3+) binding characteristics. PMID- 1517731 TI - Lanthanide ion luminescence as a probe of DNA structure. 2. Non- guanine containing oligomers and nucleotides. AB - Oligo(dC)8, oligo(dA)8, and oligo(dT)8 as well as d-CMP, d-AMP, and d-TMP, when complexed to Eu(3+), possess two classes of Eu(3+) binding environment. The binding environments consist of two classes, tight sites which coordinate two H2O molecules, and weaker sites which coordinate six or seven, analogous to the previously studied guanine-containing molecules. It is inferred that the tight class of Eu(3+) ion site observed with these oligomers and nucleotides corresponds to dimeric or polymeric structures. Comparison of the results for the guanine and non-guanine containing oligomers suggests that Eu(3+) possibly coordinates base nitrogen atoms in the former and in an outer sphere mode (hydrogen bonding via the H2O molecules coordinated to Eu(3+)) in the species examined here. PMID- 1517732 TI - Antifungal potential of binary and mixed-ligand complexes of N,2'-diphenyl acetohydroxamic acid. AB - Chelating potential of N,2'-DPAHA with 3d metal ions such as Cu(II), Ni(II), Zn(II), and Cd(II) in the presence of Gly and Phen has been investigated. These experiments were designed to study the role of the stability of mixed-ligand complexes in the modulation of its fungicidal potential. The mixed-ligand complexes were found to be more stable than binary complexes. Enhanced stability of mixed-ligand complexes of Ni(II), Co(II), Zn(II), and Cd(II) is presumably due to pi-bonding effects. In the stabilization of the Cu(II) mixed-ligand complex system, the Jahn-Tellar effect may play a vital role, in addition to pi-bonding effects. Fungicidal activity of N,2'-DPAHA and its binary complexes with Cu(II), Ni(II), and Co(II) was examined against Fusarium oxysporum using the inhibition zone technique. Binary complexes of Zn(II) and Cd(II) with N,2'-DPAHA and mixed ligand complexes M(II)-Gly or Phen-N,2'-DPAHA, where M(II) = Cu(II), Ni(II), Zn(II), Co(II), and Cd(II) were screened against Alternaria alternata by slide germination technique. All mixed-ligand complexes exhibited fungicidal activity but did not improve significantly compared to binary complexes. Synergistic action of primary and secondary ligands has increased the stability of the mixed ligand complex compared to the binary complex (1:1) of the secondary ligand (N,2' DPAHA), and the fungicidal potential of the mixed-ligand complex involving N,2' DPAHA as secondary ligand was not increased. PMID- 1517733 TI - Biological activities of trimethylselenonium as influenced by arsenite. AB - The present study was designed to evaluate three biological activities of trimethylselenonium (TMSe+): anticarcinogenicity, toxicity, and nutritional availability. These experiments were carried out in female rats both in the presence and absence of arsenite because arsenite is known to affect selenium metabolism. Supplementation with TMSe+ by itself in the diet, at levels of 20, 40, or 80 ppm Se, did not offer any protection against mammary carcinogenesis induced by dimethylbenz(a)anthracene. On the other hand, the coadministration of arsenite (5 ppm As) with the two higher levels of TMSe+ resulted in significant tumor suppression. In the acute toxicity experiment, rats were injected subcutaneously with 0.5 or 1 mg Se/kg, preceded 15 minutes earlier by arsenite at doses of 0.5, 1, or 2 mg As/kg. Although treatment with TMSe+ or arsenite alone did not produce any sign of toxicity, a synergistic toxic effect was evident with the combination. Regarding the ability of TMSe+ to restore hepatic glutathione peroxidase following selenium depletion, it was found that a dietary level of 40 ppm Se was necessary for complete recovery. The nutritional biopotency of TMSe+ was not sensitive to either up- or down-regulation by arsenite under conditions where arsenite also enhanced the anticarcinogenic activity of TMSe+. The contrasting effects of arsenite on these two end points suggest that different forms of selenium are involved. It is hypothesized that arsenite might increase the production of a critical metabolite from methylated selenides. However, there is no clear evidence at the present time to suggest whether the same intermediate(s) is responsible for both anticarcinogenicity and toxicity. PMID- 1517735 TI - Antimicrobial agents from Licaria puchuri-major and their synergistic effect with polygodial. AB - The resistance of the seeds of Licaria puchuri-major (Lauraceae) to decomposition in nature seems to be due largely to chemical defense, since its n-hexane extract contains antimicrobial principles in quantity, with a broad antimicrobial spectrum. In order to identify the active principles, the n-hexane extract was steam-distilled to yield a distillate and a residue. Subsequent bioassay indicated that the distillate retained the original broad antimicrobial activity, while the residue exhibited almost no activity. Gc-ms analysis showed that the distillate contained four phenolic compounds, seven monoterpenes, and one sesquiterpene. In contrast, the residue contained, almost exclusively, lauric acid. In the detailed antimicrobial assay with the pure compounds identified, most of them showed broad, but moderate, antimicrobial activity. Some of the components identified in the distillate were combined with polygodial [1] in order to enhance their antifungal activity. Unexpectedly, while polygodial did not synergize the antifungal activity of any of the compounds tested, the antifungal activity of polygodial was significantly increased when combined with aromatic substances such as anethole, safrole, or methyleugenol. PMID- 1517734 TI - Microcolins A and B, new immunosuppressive peptides from the blue-green alga Lyngbya majuscula. AB - Microcolin A [1] and microcolin B [2] are new immunosuppressive lipopeptides isolated from a Venezuelan sample of the blue-green alga Lyngbya majuscula. The microcolins are potent inhibitors of the murine mixed lymphocyte response and murine P-388 leukemia in vitro. Isolation and structure elucidation of 1 and 2 by nmr, mass spectral, and chemical methods are described. PMID- 1517736 TI - Chemical investigation of the metabolites from the Canadian tuckahoe, Polyporus tuberaster. AB - The metabolites of the Canadian tuckahoe, the sclerotium of Polyporus tuberaster, have been investigated. The ten-membered lactone tuckolide [1] was isolated, and its structure was determined by spectroscopic methods and confirmed by X-ray crystallography. Ergosterol, ergosterol peroxide, and several unidentified ergosterol derivatives were also obtained, along with an unidentified disaccharide. PMID- 1517737 TI - Plant anticancer agents, L. cytotoxic triterpenes from Sandoricum koetjape stems. AB - A new ring-A secotriterpene, koetjapic acid [1], and five known compounds, 3-oxo olean-12-en-29-oic acid [2] (a novel natural product), katonic acid [3], (-) alloaromadendrene, (-)-caryophyllene oxide, and (+)-spathulenol, have been isolated and characterized from a cytotoxic Et2O-soluble extract of Sandoricum koetjape stems. Of these compounds, 2 and 3 demonstrated significant cytotoxic activity against cultured P-388 cells (ED50 values of 0.61 and 0.11 microgram/ml, respectively). Significant, albeit less intense, cytotoxicity was also observed with a variety of cultured human cancer cells. The 13C-nmr chemical shifts of these triterpenes were assigned unambiguously using selective INEPT nmr experiments. Aside from compounds 2 and 3, these substances were not toxic with cultured cells. PMID- 1517738 TI - Stevisalioside A, a novel bitter-tasting ent-atisene glycoside from the roots of Stevia salicifolia. AB - A new acetylated ent-atisene glycoside, stevisalioside A [1], has been isolated as a bitter-tasting principle from Stevia salicifolia roots. The structure was established by the interpretation of spectral data, with the nmr assignments of this compound being based on 1H-1H COSY, 1H-13C HETCOR, and selective INEPT experiments. A rearrangement product 4 of the aglycone moiety obtained by alkaline hydrolysis supported the structure of 1. This is the first report of the occurrence of an atisane-type diterpene from the genus Stevia. PMID- 1517739 TI - Cytotoxic quassinoids from Cedronia granatensis. AB - The NCI in vitro primary disease-oriented antitumor screen has been used to select and guide the fractionation of the organic and aqueous extracts of Cedronia granatensis. Two quassinoids, sergiolide [1] and isobrucein B [2], to which the screening panel cell lines exhibited up to a 1000-fold range of differential sensitivity, were isolated. At concentrations of 10(-5)-10(-8) M, the compounds typically produced LC50-level responses against a majority of the melanoma lines and several of the colon, lung, and other solid tumor lines. These and related quassinoids may, therefore, be of interest for in vivo evaluation in appropriate xenograft tumor models. PMID- 1517740 TI - New tetrasaccharide flavonol glycoside from Epimedium acuminatum. AB - A new tetrasaccharide flavonol glycoside was isolated from the aerial parts of Epimedium acuminatum, along with three known flavonoids. The structure of the new compound, named acuminatoside [1], was established to be anhydroicaritin-3-O alpha-L-rhamnopyranosyl(1----2)-alpha-L-rhamno pyranoside-7- O-beta-D glucopyranosyl-(1----2)-beta-D-glucopyranoside by means of spectroscopic techniques (uv, eims, fdms, fabms, 1H nmr, 1H-1H COSY, 2D-J, 13C nmr, APT, and 1H 13C HETCOR) and chemical methods (acid hydrolysis, enzymatic hydrolysis, and tlc densitometry). The known compounds were identified as icariin, epimedoside A, and kaempferitrin. PMID- 1517741 TI - Renal excretion of stevioside in rats. AB - The renal excretion of stevioside, a glycoside extracted from the leaves of Stevia rebaudiana, and its effect on renal excretion of several substances, was studied through clearance techniques in Wistar rats. After a control period, stevioside was infused iv at four concentrations (4, 8, 12, and 16 mg/kg). During all the experiments no significant changes in inulin clearance (CIn) were observed. The stevioside infusion induced a significant increase in the p aminohippuric acid clearance (CPAH), fractional sodium excretion (FeNa+), urinary flow as percent of glomerular filtration rate (V/GFR), and glucose clearance (CG) when compared to controls, but these effects were absent with the dose of 4 mg/kg. The stevioside clearance (CS) was higher than the CIn and lower than the CPAH at all the doses employed in this study. These results indicate that the stevioside is secreted by renal tubular epithelium and induces diuresis and natriuresis and a fall in renal tubular reabsorption of glucose. PMID- 1517742 TI - Inhibition of angiotensin-I-converting enzyme by tetrahydroxyxanthones isolated from Tripterospermum lanceolatum. AB - Five tetrahydroxyxanthones, 3,4,6,7-tetrahydroxyxanthone [1], 1,3,5,6 tetrahydroxyxanthone [2], 3,4,5,6-tetrahydroxyxanthone [3], 1,3,6,7 tetrahydroxyxanthone [4], and 2,3,6,7-tetrahydroxyxanthone [5] isolated from Tripterospermum lanceolatum inhibited angiotensin-I-converting-enzyme activity in a dose-dependent manner. The mode of inhibition of the tetrahydroxyxanthones (THXs) was found to be competitive inhibition. When the tetrahydroxy groups of THXs were blocked with acetyl groups, the angiotensin-I-converting-enzyme inhibitory activity was abolished, suggesting that the tetrahydroxy groups are indispensible for the inhibitory activity. PMID- 1517743 TI - Emodin, a protein tyrosine kinase inhibitor from Polygonum cuspidatum. AB - Bioassay-directed fractionation of a Chinese medicinal plant, Polygonum cuspidatum (Polygonaceae), has led to the discovery of an anthraquinone, emodin [1], as a strong inhibitor of a protein tyrosine kinase (p56lck) partially purified from bovine thymus. Comparison of the IC50 values of emodin for protein tyrosine kinase inhibitory activity with physcion [2] and emodin-O8-D-glucoside [3], also isolated from the same plant, reveal the importance of the hydroxyl groups at C-6 and C-8 for the observed activity. PMID- 1517744 TI - On the role of monocytes/macrophages in the pathogenesis of central nervous system lesions in hereditary cystatin C amyloid angiopathy. AB - The pathogenesis of the deposition of a variant cystatin C as amyloid in hereditary cystatin C amyloid angiopathy (HCCAA) is not known. To address this question the synthesis and secretion of cystatin C in cultured monocytes from 9 carriers of the mutated cystatin C gene (5 symptomatic and 4 asymptomatic) was examined. The quantity of cystatin C in cells and supernatants was determined by the ELISA method, Western blots were done and selected samples immunostained for cystatin C. Monocytes from individuals carrying the gene defect synthesized cystatin C that was apparently not truncated, a form found in the cerebral amyloid deposits in HCCAA, but showed a distinctly lower rate of cystatin C synthesis than monocytes from healthy controls. The main difference was that the quantity of cystatin C was significantly lower in the supernatants in monocyte cultures from carriers of the gene defect than from healthy controls, possibly due to a partial block in its secretion. This abnormal processing of the cystatin C could explain the low cerebrospinal fluid levels of cystatin C in HCCAA and might be a part of the pathogenetic pathway of amyloid deposition. Furthermore it could, through a lower extracellular concentration of this inhibitor of cysteine proteinases, contribute to destruction of the amyloidotic blood vessels, leading to the most serious clinical manifestation in HCCAA, intracerebral hemorrhage. PMID- 1517745 TI - Extrapyramidal system involvement in motor neuron disease. AB - Three cases of motor neuron disease (MND), in which neuropathological findings were atypical, are reported. The first case manifested widespread and severe degeneration of the spinal cord, as in spinal fibrosis. Case 2 revealed severe degeneration of the pyramidal tract with many spheroids, which made it difficult to differentiate from primary amyotrophic lateral sclerosis. The last case revealed degeneration of the nigro-pallido-luysian system, even though no clinical manifestation of extrapyramidal and/or cerebellar symptoms had been noted throughout the clinical course. In MND, degeneration might occur in various locations other than the motor system. PMID- 1517746 TI - Creutzfeldt-Jakob disease presenting as Wernicke-Korsakoff syndrome. AB - A 47-year-old man began to suffer from progressive truncal ataxia and mental alterations typical of Wernicke-Korsakoff syndrome. He showed confusional state, hallucinations, delirium of jealousy and a serious impairment of recent memory. The symptomatology lasted 13 months, but only in the last weeks was it complicated by myoclonias. Triphasic pseudoperiodic sharp-waves characterized the EEG-recordings only in the final stage. Macroscopic examination of the brain showed marked atrophy of the mammillary bodies and superior vermis. However, the histological features were consistent with Creutzfeldt-Jakob disease (CJD) with focal accentuation of the changes in the latter structures. This case supports the hypothesis that CJD-changes begin focally in the CNS and, subsequently, spread along neuronal pathways, probably via central axons. Only in the final stage does the pathological process involve most parts of the gray matter. A focal accentuation of the CJD process in the cerebello-mammillo-thalamic system caused in this case a Wernicke-Korsakoff-like syndrome. PMID- 1517747 TI - Histopathology and fine structure of the brain in six cases of Creutzfeldt-Jakob disease from western India. AB - Light and electronmicroscopic changes in 5 formalin-fixed brains, and one glutaraldehyde-fixed brain biopsy, from patients with Creutzfeldt-Jakob disease in the age range of 45 to 65 years, are described. These 6 patients (out of 7 reported clinically earlier and 2 unreported) had classical manifestations with progressive dementia, pyramidal signs and myoclonic jerks. Light microscopy showed neuronal and nerve fibre loss, moderate or severe spongiform change, astrocytic proliferation and absence of inflammatory reaction. Electronmicroscopy confirmed the characteristic membranous profiles of the 'cysts' and 'daughter cysts' constituting the spongiform change. The membranes were generally dark and thin, either concentrically arranged or splitting and with stray pale broad segments. The one glutaraldehyde-fixed brain biopsy specimen showed cisterns of RER in close proximity to these 'cysts', suggesting the source of proteinous material of these membranes. Though mainly in the neurones and dendrites of the cortex, at times they were seen in the myelinated fibres also, a few of which showed dystrophic axons bearing dense bodies. One of the 6 patients had cerebellar signs also, and a total duration of the neurological illness of 36 months, as against 2-8 months in the 5 other patients. The histopathological examination of her brain revealed less spongiform change, and many cerebral cortical glial whorls, the centre of which showed PAS-positive and congo-red positive material representing amyloid. Fine structural examination confirmed the glial whorls, and the filamentous nature of amyloid in the plaques, which resembled Kuru plaques. All brains also showed more or less intraneuronal lipofuscin. PMID- 1517748 TI - Neuropathological background of twenty-seven centenarian brains. AB - The neuropathological features of 27 centenarian brains were investigated. They were found to have no fundamental differences from the brains of younger elderly individuals. It was noted that 3 centenarian brains showed no apparent senile changes or ischemic lesions and this group was designated "supernormal" centenarians. In contrast, there were 6 centenarian brains with numerous senile plaques in the cerebral cortex, a finding resembling that seen in senile dementia of the Alzheimer type (SDAT). However, these brains had only a few neurofibrillary tangles mainly in the hippocampus and the medial temporal lobe, and therefore were not affected by SDAT. These subjects were not truly demented. It was considered that these brains showed the upper limit of normal ageing, while the "supernormal" centenarians showed the lower limit. In addition, idiopathic Parkinson's disease was diagnosed pathologically in 4 subjects who did not show any clinical symptoms of this disease. Finally, 2 out of 5 cases with dementia developed it secondary to subdural haematoma. PMID- 1517749 TI - Characterization of a transthyretin-related amyloid fibril protein from cerebral amyloid angiopathy in type I familial amyloid polyneuropathy. AB - Recently, it has been reported that transthyretin (TTR)-immunoreactive amyloid deposition with cerebral amyloid angiopathy in central nervous system is a common pathological finding in type I familial amyloid polyneuropathy (FAP). In the present study, we performed isolation and sequence analysis of TTR-related amyloid fibril protein from the meninges of a patient with type I FAP. Purified major amyloid fibril protein had a molecular weight of 15 kDa. Complete sequence analysis revealed that this amyloid fibril protein was a variant TTR with a single amino acid substitution of methionine for valine at position 30. This variant TTR is a previously unrecognized as cerebrovascular amyloid fibril protein. Furthermore, the patients with type I FAP are well known to have the variant TTR in the serum. These suggest that cerebrovascular amyloid fibril protein in type I FAP may derive from a serum precursor. PMID- 1517750 TI - Improvement in motor evoked potentials and clinical course post-steroid therapy in multiple sclerosis. AB - Motor evoked potentials (MEP) were recorded in 23 patients with definite relapsing multiple sclerosis before and after treatment with a short course of high dose of methylprednisolone. MEP were performed together with clinical examination just before treatment, and 6 and 60 days later. The following results were observed: (1) a statistically significant relationship between the corticospinal deficit and the alteration in MEP, (2) a significant improvement in latency of MEP by day 6, (3) a significant correlation between the change in the Kurtzke disability scale rating and the improvement in MEP. The results provide further evidence for the possible effectiveness of short courses of high dose corticosteroids in the treatment of relapses of multiple sclerosis and the usefulness of MEP in its assessment. PMID- 1517751 TI - Muscular involvement in lysosomal acid lipase deficiency in rats. AB - We investigated the pathological and biochemical changes of skeletal muscle in rats with lysosomal acid lipase deficiency, which is an animal counterpart of human Wolman's disease. In the affected rats, the acid lipase activity for three different substrates, 4-methylumbelliferyl-oleate (18.9% of the normal control level), [14C]cholesteryl oleate (23.5%), and [14C]triolein (26.9%), was similarly decreased in the lysosomal fraction of skeletal muscle which was obtained by differential centrifugation. Histochemical studies showed that acid phosphatase activity was high in the endomysium and perimysium and in some muscle fibers. Some fibers showed vacuolar degeneration resembling "rimmed vacuoles". Ultrastructural studies demonstrated many membrane-bound lipid droplets in the muscle fibers, especially in the subsarcolemmal space, indicating that a low density lipoprotein (LDL) uptake pathway apparently existed in the muscle cells. However, such lipid accumulation was much greater in the interstitial cells and the endothelial cells. This distribution also suggests that LDL/cholesterol is supplied to muscle cells predominantly through endothelial cells. PMID- 1517752 TI - Detection and severity of low frequency fatigue in the human adductor pollicis muscle. AB - The sensitivity of electrical stimulation tests for detecting low frequency fatigue (LFF) and its duration were examined in the adductor pollicis muscle of ten normal subjects. Supramaximal stimulation was applied to the ulnar nerve at the wrist and values for test stimulation force ratios of 10:100 Hz, 15:100 Hz and 20:50 Hz (2 sec at each frequency with 5 min rest between each ratio) were obtained for fresh muscle. Fatigue was then induced by voluntary isometric contractions at 50% maximal voluntary force (MVC) repeated until only 30% MVC could be achieved. Contractions lasted 10 sec with 5 sec rest between each. The three test ratios were then repeated to monitor recovery at intervals up to 72 h after activity. High frequency forces returned to fresh values by 24 h but low frequency forces were all still significantly reduced. Forces at 10 and 15 Hz were still significantly reduced at 48 and 72 h (10 Hz greater than fatigue than 15 Hz). The low/high frequency ratios, calculated once 50 and 100 Hz forces had recovered, also demonstrated differences in recovery rates. Repeatability tests indicated that 10 Hz force was more variable than other frequencies and forces at all stimulation frequencies were repeatable on different days with a coefficient of variation of less than 15%. Values for the 15:100 Hz ratio from fresh muscle in 22 normal subjects were 0.48 +/- 8. The 15:100 Hz ratio is suggested as the most appropriate test ratio for detecting LFF since 15 Hz force is more sensitive than 20 Hz and more stable than 10 Hz. PMID- 1517753 TI - Serum factors responsible for unusual induction of plasminogen activator activity in tuberous sclerosis. AB - Peripheral blood lymphocytes derived from tuberous sclerosis (TS) patients showed unusually high levels of plasminogen activator (PA) activity after treatment with N-methyl-N'-nitro-N-nitrosoguanidine (MNNG). Serum obtained from peripheral blood of TS patients also enhanced the PA activity level when normal control lymphocytes were incubated with the serum prior to MNNG treatment. Factors exhibiting the enhancing activity were eluted with a solution of about 0.70 M KCl on dye-ligand chromatography, which were inhibited on incubation with an anti human interferon (HuIFN)-beta antibody, but not with anti-HuIFN-alpha or anti HuIFN-gamma antibodies. Unlike in the case of HuIFN-beta, the eluted samples did not possess antiviral or anticellular activity. Thus, it seems likely that serum from TS patients contains factors which are responsible for the unusual PA induction and which have a similar epitope to HuIFN-beta. PMID- 1517754 TI - Juvenile parkinsonism: ventricular CSF biopterin levels and clinical features. AB - Total biopterin (T-BP) levels in the ventricular cerebrospinal fluid (CSF) and clinical features of 19 patients with juvenile parkinsonism (JP: Parkinson's disease manifesting below the age of 40) were evaluated and compared with 61 patients with classical Parkinson's disease (classical PD: symptoms developing at the age of 40 or above). The JP patients were divided into two subgroups: JP-I; those with good response to levodopa followed by marked motor fluctuations and dopa-induced dyskinesias (DID), JP-II; those with milder response than JP-I with less fluctuations and DID being more similar to classical PD. Both of the mean ventricular CSF T-BP concentrations in the JP and classical PD patients were significantly lower than that in neurological controls. Moreover, the mean T-BP level in the JP-I was markedly lower than that in the JP-II or classical PD. Total biopterin levels revealed a gaussian distribution in the classical PD. However, a bimodal distribution was noted in the JP, with the lower peak consisting of only JP-I patients. These results seem to indicate that JP-II represents early-onset classical PD, while JP-I represents a distinct subgroup having a different physiopathology from classical PD. PMID- 1517755 TI - Dystrophin isoforms and/or cross-reactive proteins on neurons and glial cells in control and mdx central nervous systems. AB - We studied the central nervous system (CNS) of control mice in comparison with that of mdx mice, immunohistochemically and immunoelectrophoretically, using 5 kinds of polyclonal antibodies against dystrophin (DMDP-II, 60-kDa, 30-kDa, P-20 and DMDP-IV) to determine whether or not and, if so, how dystrophin exists in the central nervous system. A positive dystrophin reaction was seen on the neurons and glial cells in both control and mdx tissue, without any immunohistochemical difference. In control mice, Western blot analysis showed two relatively clear bands corresponding to 400-kDa, with all 4 antibodies used (60-kDa, 30-kDa, P-20 and DMDP-IV), and 280-kDa, with 3 of them, the exception being 30-kDa, and 2 other faint bands corresponding to larger M(r) than 400-kDa, with 3 of them, the exception being P-20, respectively. In the mdx CNS, the 400-kDa band was absent, the other 3 bands being seen. The results suggest that dystrophin really exists in the control CNS, and some dystrophin isoforms or cross-reactive proteins exist on the neurons and glial cells in mdx as well as control mice. The localization of dystrophin in CNS also suggests its physiological function in the conduction system rather than a mechanical one, and a defect of it in CNS is a possible cause of the mental retardation in Duchenne muscular dystrophy. PMID- 1517756 TI - Effects of anaesthetics, anticonvulsants and glutamate antagonists on kainic acid induced local and distal neuronal loss. AB - A semi-quantitative estimation has been made of the effect of anaesthetics, anticonvulsants and glutamate antagonists on the extent of neuronal loss in the hippocampus caused by the local injection of the excitotoxin kainic acid, and on the vulnerability of neurons in various extrahippocampal regions due to the resulting seizure activity. Following the intrahippocampal injection of 0.47 nmol kainic acid (a submaximal dose), the amount of neuronal loss in the dorsal hippocampus was greater when given under the short-acting anaesthetics halothane and ketamine (a non-competitive glutamate antagonist), than when given under pentobarbital anaesthesia (with or without co-administration of ketamine (30 mg/kg)). When kainic acid was injected under halothane or ketamine anaesthesia a greater number of extrahippocampal limbic regions (distal toxicity) were also affected, usually on the ipsilateral side, and the extent of damage in each of these regions was generally more extensive. The anticonvulsants MK 801 and diazepam, or multiple injections of ketamine over a period of 5 h, decreased both the local and distal toxicity of kainic acid injected under short duration anaesthesia, to levels similar to those found under pentobarbital anaesthesia. However, these compounds, even at high doses, could not reliably prevent all seizure-related damage in extrahippocampal areas. PMID- 1517757 TI - Peripheral neuropathy with giant axons and cardiomyopathy associated with desmin type intermediate filaments in skeletal muscle. AB - A sporadic case (female, aged 14 years) is reported who was affected by myopathy, restrictive cardiomyopathy and sensory motor polyneuropathy. A muscle biopsy showed accumulation of osmiophilic granular and filamentous material on electron microscopy, which stained positively in immunofluorescence for desmin. Increased desmin phosphorylated isoforms have been demonstrated by one- and two-dimensional electrophoresis. Sural nerve biopsy showed a peripheral neuropathy with giant axons, filled with closely packed neurofilaments. Clinical and morphological aspects of this new disease entity are discussed with regards to the classical form of giant axonal neuropathy and to other conditions of peripheral neuropathy with giant axons. PMID- 1517758 TI - Immunohistochemical expression of microtubule-associated protein 5 (MAP5) in glial cells in multiple system atrophy. AB - An immunohistochemical study focusing on glial cells was performed using monoclonal antibodies against microtubule-associated proteins (MAP1, MAP2 and MAP5), transferrin, leukocyte common antigen (LCA) and glial fibrillary acidic protein (GFAP) in 5 cases of multiple system atrophy (MSA) exhibiting olivopontocerebellar atrophy and striatonigral degeneration. An antibody to MAP5, a fetal antigen in developing brain, was strongly demonstrated in the glial cytoplasmic inclusions (GCIs) which have recently drawn a great deal of attention and were observed in all 5 cases of MSA. Moreover, MAP5-positive glial cells (MAP5-Gs) were present in significantly higher number than in the controls in various regions where GCIs were found, predominantly in putamen, substantia nigra, cerebellar white matter and internal capsule. LCA and transferrin, markers of microglia and oligodendroglia, respectively, were immunohistochemically detected in some MAP5-Gs. GFAP, on the other hand, was not expressed in MAP5-Gs at all. These findings suggest that MAP5-Gs consist of reactive microglia and oligodendroglia. Our study is the first to demonstrate immunohistochemical detection of MAP5 in glial pathological changes in MSA. PMID- 1517759 TI - Inhibition of stimulated human leukocyte hydrogen peroxide generation by a novel antioxidant, OPC-14117. AB - Oxygen free radicals generated by leukocytes may contribute to tissue injury after central nervous system (CNS) focal ischemia or trauma. Inhibiting oxygen free radicals has improved outcome in experimental models of these conditions and antioxidant therapy appears promising. We evaluated the ability of a novel antioxidant, OPC-14117, to reduce hydrogen peroxide (H2O2) production by stimulated human polymorphonuclear (PMN) leukocytes and monocytes. Stimulated PMN and monocytes were incubated with several concentrations of OPC-14117 for 20 min and H2O2 production, nmol/1 x 10(6) cells/30 min, was measured. OPC-14117 significantly reduced PMN H2O2 production (P less than 0.001) and monocyte H2O2 production (P less than 0.05). A dose response relationship was observed for both leukocytes, as the 100 microM drug concentration was significantly (P less than 0.05) more effective than the 10 microM concentration. These results demonstrate that OPC-14117 inhibits H2O2 generation by stimulated human leukocytes and support further studies of its effects in disorders such as CNS focal ischemia and trauma, conditions where antioxidant therapy may be beneficial. PMID- 1517760 TI - What is the validity of an "abnormal" evoked or event-related potential in MS? Auditory and visual evoked and event-related potentials in multiple sclerosis patients and normal subjects. AB - The predictive validity of evoked potentials (EPs) and event-related potentials (ERPs) in multiple sclerosis (MS) has not yet been fully investigated, as only the sensitivity of these tests has sofar been reported. EPs (short, middle and long latency auditory evoked potentials and visual evoked potentials) and ERPs (visual and auditory) were studied in 19 controls and 30 multiple sclerosis (MS) patients. Abnormality thresholds of peak latencies were defined on the basis of the mean plus 2 or 3 standard deviations, based on data from the control group. The effects of changing the latency thresholds and including the absence of peaks in the abnormality definition were assessed. In accordance with earlier reports we found a high sensitivity (up to 93% for bimodal combined EPs and 47% for combined ERPs). False positive rates of separate peaks were low and conformed to expectation. However, combining separate peak measurements increased false positive rates of EPs and ERPs to unacceptably high levels (up to 58% for combined EPs and 32% for combined ERPs). Positive likelihood ratios for bimodal EPs were low (between 1.6 and 4.0, depending on the abnormality definition). They ranged from 1.4 to 2.2 for bimodal ERPs. Abnormal combined EPs or ERPs were therefore not the reliable indicators of functional damage that they are supposed to be. Separate EPs were much more reliable in this respect. ERPs failed to distinguish between the groups, either separately or in combination. Changing the latency threshold and including absent peaks in the abnormality definition influenced the abnormality rates in both groups.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1517761 TI - Are event-related potentials in multiple sclerosis indicative of cognitive impairment? Evoked and event-related potentials, psychometric testing and response speed: a controlled study. AB - Bimodal event-related potentials (ERPs), together with evoked potentials (EPs), measures of motor speed (tapping test, EMG latencies and reaction times (RT)), and psychometric test results were studied in a group of 30 multiple sclerosis (MS) patients and 19 controls. ERPs have been advocated as objective tests of cognitive function. In the present study ERPs were compared with the results of psychometric tests, which have a proven validity in measuring aspects of cognitive function that are important in daily life. Abnormal EMG, RT and tapping speed confirmed that motor aspects of performance were slowed in the MS group. In contrast, cognitive non-motor variables such as Raven-IQ and MQ were not significantly abnormal. The proportions of abnormal ERP N2 and P3 latencies did not differ between the groups. It is concluded that the slow performance of MS subjects is therefore most likely not due to cognitive speed decrement, but to motor, executive impairments. No significant relationships between ERP latencies and psychometric test results were found. This held even for a subgroup of 5 MS patients with psychometrically established cognitive impairments. Based on these results, we query the relevance of ERPs as subtle indicators of cognitive impairment in MS. PMID- 1517762 TI - Topography of unmyelinated axons in regenerated soleus nerves of the rat. AB - The topography of unmyelinated axons on cross sections of normal and regenerated soleus nerves of rat was studied by electron microscopy. The experimental nerves were crushed and assessed after 1-19 weeks. Unmyelinated axons in normal nerves were arranged in few groups. Nerve crush did not alter the arrangement of unmyelinated axons in the proximal nerve. Distal to the crush lesion, however, the unmyelinated axons became scattered throughout the entire cross section. The grouping of unmyelinated axons within the cross section was quantitated by means of a "clustering factor", defined as the percentage of unmyelinated axons in those 10% of the cross-sectional area which had the highest density of unmyelinated axons. The results indicate that unmyelinated axons during regeneration do not follow their original pathways. PMID- 1517763 TI - Linkage analysis of distal hereditary motor neuropathy type II (distal HMN II) in a single pedigree. AB - We describe a six generation family affected with the autosomal dominant form of distal hereditary motor neuropathy type II (distal HMN II). The distal HMN shows similarities with the hereditary motor and sensory neuropathies type I and II (HMSN I and HMSN II) or Charcot-Marie-Tooth disease type 1 and 2 (CMT 1 and CMT 2) and with some proximal HMN or spinal muscular atrophies (SMA). Gene loci have been assigned to chromosomes 1q, 17p, and 19q for CMT 1 and to chromosome 5q for recessive SMA. In this study we excluded all four regions for the presence of distal HMN II, indicating that this neuropathy is genetically different from CMT 1 and recessive SMA. PMID- 1517764 TI - Co-activation of ipsi- and contralateral muscle groups during contraction of ankle dorsiflexors. AB - Seventeen adult, healthy subjects, age 38.4 +/- 0.24 years (mean +/- SEM) 7 of which were females, were studied. Each subject was seated on a specially designed chair with trunk and legs fixed and the foot strapped to a rigid plate that was attached to a load cell. The position of the strap was adjusted so as to lie across the foot at the level of the metatarsal bones. The knee and ankle joints were adjusted to 90 degrees. To record EMG activity, pairs of surface electrodes were placed over the belly of both the right and left tibialis anterior, quadriceps, hamstring and contralateral triceps surae muscles. Two experimental paradigms were used, A and B. In A the subject was asked to sustain maximum voluntary contraction (MVC) of the ankle dorsiflexors until the force decreased to 50% of the initial value; in B the subject was asked to carry out contractions of the ankle dorsiflexors for 6 seconds followed by 4 sec relaxation periods. The initial contraction was 20% of MVC followed by 40, 60, 80 and 100% of MVC which represented one cycle. The subject was asked to repeat this cycle 10 times. Voluntary contraction of ankle dorsiflexors was regularly accompanied by activation of other muscles, usually first in the same leg, later in the contralateral leg during MVC of ankle dorsiflexors. When intermittent contractions with step wise increments of force developed by the ankle dorsiflexors were carried out, co-activation of ipsilateral and contralateral muscle groups occurred before the force of the contracting muscles decreased.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1517765 TI - Acoustic myography of the human quadriceps muscle during intermittent fatiguing activity. AB - Integrated acoustic myography (IAMG) and electromyography (IEMG) were recorded over rectus femoris (RF) in six healthy subjects during a series of intermittent isometric contractions of quadriceps. Contractions were held for 10 sec with 10 sec rest between each, commencing at 75% maximum voluntary contraction (MVC) force and continuing to 40% MVC. The IAMG activity initially decreased (75%-60% MVC) in a linear relationship (r = 0.9) with fatigue (i.e. force loss) but then plateaued and increased once force fell below 52% MVC. The AMG/force relationship for the whole fatiguing protocol (i.e. 75%-40% MVC) was quadratic (r = 0.87). The IEMG also showed a quadratic relationship with force (r = 0.85) but activity initially increased before decreasing. The results of the present study quantify the relationship between AMG and force in quadriceps during fatigue from intermittent contractions commencing at 75% MVC. The findings confirm previous observations that AMG decreases with fatigue during strong contractions but the quadratic relationship found in the present study differs to that for other muscles during sustained contractions. The results also suggest that simultaneous recordings of AMG and EMG may help distinguish central and peripheral fatigue. Acoustic myography may therefore be a useful non-invasive monitor of force during early fatiguing activity using the present protocol but the need to study AMG during fatigue of different muscles and force levels is stressed. PMID- 1517766 TI - Interferon-gamma in cerebrospinal fluid without pleocytosis in scrub typhus. AB - We detected immunoreactive interferon-gamma (IFN-gamma) both in cerebrospinal fluid (CSF) and in serum of 5 patients with scrub typhus, one with meningitis and 4 other cases with neither CSF pleocytosis nor blood-CSF barrier dysfunction. Our data suggest intrathecal synthesis of IFN-gamma without pleocytosis which implies occult cerebral involvement in scrub typhus. PMID- 1517767 TI - Expression of cell surface and cytoskeleton developmentally regulated proteins in adult centronuclear myopathies. AB - In order to evaluate the developmental status of myofibers in 3 cases of adult centronuclear myopathies (CNM) with type I predominance, we searched for the expression of (a) developmentally regulated cytoskeleton proteins (myosin heavy chains (MHC), vimentin, desmin), and (b) cell surface molecules (neural cell adhesion molecules isoforms, NCAM). Desmin intermediate filaments were overexpressed in some fibers with centrally located nuclei and radially organized. Muscle fibers do not express vimentin. These findings were not observed in muscle biopsies from disease controls with numerous central nuclei. Few myofibers (less than 5%) expressed developmental MHC together with either embryonic NCAM or adult NCAM and rare fibers only expressed adult NCAM. Most of the remaining fibers neither expressed NCAM nor developmental MHC but were slow MHC positive. These features do not favor the hypothesis of a general arrest of muscle fiber maturation in adult CNM. It is more likely that fibers undergo a very slow developmental process with a long delay of innervation as shown by some fibers with NCAM expression. Nevertheless, innervation appears to be successful, as suggested by the large number of NCAM negative fibers. Moreover, the abnormal myofiber distribution could be related to this functional disturbance of innervation. PMID- 1517768 TI - Distribution of cerebrospinal fluid oligoclonal IgM bands in neurological diseases: a comparison between agarose electrophoresis and isoelectric focusing. AB - Isoelectric focusing (IEF) and agarose gel electrophoresis were used to detect oligoclonal IgM bands in cerebrospinal fluid and serum samples from 850 patients with diverse neurological diseases. Oligoclonal IgM bands in cerebrospinal fluid were mainly detected in patients with infectious and inflammatory disorders of the nervous system. Both IEF and agarose electrophoresis revealed similar frequencies of oligoclonal IgM bands. Bands detected by IEF were mainly seen in the anodal range. Despite higher resolving capacity, IEF was less specific than agarose gel electrophoresis. It is concluded that oligoclonal IgM bands have important diagnostic significance and that agarose gel electrophoresis is more suitable for their detection in routine clinical work and use in differential diagnosis. PMID- 1517769 TI - Neuropathology in depth: the role of confocal microscopy. PMID- 1517770 TI - Neuropathology in depth: the role of confocal microscopy. AB - This review surveys the rapidly increasing applications of confocal microscopy in neuropathology and related areas of experimental neurology. The ability of this new instrument to "optically section" thick samples has opened up to microscopic examination a wide range of previously difficult specimens. The basic operating principle, trading field of view for axial resolution, is illustrated with a simple schematic comparison of conventional and confocal microscopes. Images can be collected in several different modes, utilizing fluorescence, reflectance, or transmitted light. The majority of the applications in neuropathology to date have focused on immunocytochemical labeling with peroxidase or fluorescent markers. New methods of specimen preparation designed explicitly for the confocal microscope are just beginning to appear. The trend toward new techniques that fully exploit the superior performance of confocal microscopes is expected to accelerate, which will quickly establish the confocal microscope as a routine laboratory tool for the neuropathologist. PMID- 1517771 TI - Malignant glioma-derived soluble factors regulate proliferation of normal adult human astrocytes. AB - Malignant gliomas are characteristically surrounded by marked gliosis. To assess whether glioma-derived products contribute to the proliferation of astrocytes, a feature of the gliosis response, we evaluated the influence of culture supernatants from malignant human glioma lines and tumor cyst fluids collected from two patients with glioblastoma multiforme on the proliferation of non transformed adult human astrocytes. Both the culture supernatants and cyst fluids significantly increased DNA synthesis in astrocytes as assessed by a double immunofluorescence glial fibrillary acidic protein-bromodeoxyuridine technique. The net proliferative effect mediated by glioma cell line supernatants was tumor growth phase-dependent, being preferentially expressed during the logarithmic phase of glioma cell growth. Specific growth factor molecules and cytokines known to be secreted by gliomas (epidermal growth factor, fibroblast growth factor, platelet-derived growth factor, transforming growth factor-beta, interleukin-6, and tumor necrosis factor-alpha) could not reproduce the mitogenic effects of the glioma-derived soluble factors. Cytokines which can induce DNA synthesis by adult human astrocytes in vitro, gamma-interferon and interleukin-1, were not detected in the culture supernatant of glioma lines used in this study. In conjunction with the documented effects of glioma products on endothelial and lymphoid cells, the current study suggests that soluble glioma products can contribute to the production of surrounding gliosis observed in vivo. PMID- 1517772 TI - Inherited neuroaxonal dystrophy in C6 deficient rabbits. AB - We report the occurrence of a progressive neurological syndrome clinically characterized by subacute motor neuropathy in offspring of C6 deficient rabbits. On the basis of the pedigree analysis, the disease appears to be genetically transmitted, most probably with an autosomal recessive mode of inheritance. Pathological studies of affected animals revealed: transmitted, most probably with an autosomal recessive mode of inheritance. Pathological studies of affected animals revealed: 1) severe axonal degeneration in the sciatic nerve system involving mainly motor fibers; 2) occasional peripheral axonal enlargement closely associated with axonal degeneration; 3) presence of structured abnormal material in normal-size myelinated fibers of central nervous system (CNS) and peripheral nervous system (PNS); and 4) widespread occurrence of dystrophic axons and axonal spheroids in the gray matter of CNS. By ultrastructural examination, dystrophic axons are filled with tubulovesicular material, stalks of parallel membranes and dense bodies similar to what is described in human neuroaxonal dystrophies (NAD). The disease manifested by C6 deficient rabbits may represent an animal model of primary human NAD. PMID- 1517773 TI - Perineurial window: demyelination in nonherniated endoneurium with reduced nerve blood flow. AB - The perineurial window, created by surgical incision of the perineurial sheath allowing its contents to herniate into the epineurial space, provides an experimental model of primary demyelination, the cause of which is unclear. Because the injury is localized and involves distortion of tissue at the lesion site, ischemia is suspected as a cause of demyelination. To study the mechanism of demyelination in the perineurial window model, we measured nerve blood flow (NBF) with a laser Doppler flowmeter before and after perineurial rupture in rat sciatic nerve and assessed the spatial distribution of demyelinated fibers, particularly in the nonherniated portion of the endoneurium. Nerve blood flow at the site of the perineurial window was reduced significantly with an average level of NBF approximately 50% of presurgical values 10 minutes, 60 minutes and 6 hours after surgery. By light microscopic examination, most nerve fibers that herniated through the perineurial window underwent demyelination by 7 days. In addition, focal lesions of subperineurial demyelination were found in the nonherniated endoneurium in the adjacent subperineurial region and proximally and distally to the perineurial window. Endoneurial vessels adjacent to the perineurial incision appeared to be compressed. We suggest that ischemia contributes to the process of demyelination in the perineurial window model. PMID- 1517774 TI - Biology of adult human microglia in culture: comparisons with peripheral blood monocytes and astrocytes. AB - We have compared phenotypic and functional properties of surgically derived adult human microglia to autologous and allogenic peripheral blood-derived monocytes and to astrocytes derived from the same surgical resection. We found that microglia differed from peripheral blood monocytes with respect to adhesion properties and survival rates in vitro. Microglia, similar to resident macrophages in different tissues, expressed many but not all (CD4, Leu-M3, non specific esterase) monocyte/macrophage associated markers tested, a pattern similar to that of terminally differentiated cells of this lineage. As with other human tissue macrophages, but in contrast to astrocytes, microglia did not undergo DNA synthesis in vitro, assessed using BrdU incorporation. Under basal culture conditions the majority of microglia of all morphologic subtypes (ameboid, bipolar, ramified) expressed MHC class II molecules; by flow cytometric analysis, mean fluorescence intensity of these cells was less than that of blood monocytes (relative to isotype control). In vitro MHC class II antigen expression on microglia, under basal and interferon gamma activating conditions, was greater than on astrocytes. Freshly derived T cells cultured with 1-10% autologous microglia plus Candida albicans underwent active proliferation, indicating the functional capacity of the microglia to serve as antigen-presenting cells. PMID- 1517775 TI - An approach to computer-aided inhibitor design: application to cathepsin L. AB - We have developed an approach to search for molecules that can be used as lead compounds in designing an inhibitor for a given proteolytic enzyme when the 3D structure of a homologous protein is known. This approach is based on taking the cast of the binding pocket of the protease and comparing its dimensions with that of the dimensions of small molecules. Herein the 3D structure of papain is used to model cathepsin L using the comparative modeling technique. The cast of the binding pocket is computed using the crystal structure of papain because the structures of papain and the model of cathepsin L are found to be similar at the binding site. The dimensions of the cast of the binding site of papain are used to screen for molecules from the Cambridge Structural Database (CSD) of small molecules. Twenty molecules out of the 80,000 small molecules in the CSD are found to have dimensions that are accommodated by the papain binding pocket. Visual comparison of the shapes of the cast and the 20 screened molecules resulted in identifying brevotoxin b, a toxin isolated from the 'red tide' dinoflagellate Ptycho brevis (previously classified as Gymonodium breve), as the structure that best fits the binding pocket of papain. We tested the proteolytic activity of papain and cathepsin L in the presence of brevotoxin b and found inhibition of papain and cathepsin L with Kis of 25 microM and 0.6 microM, respectively. We also compare our method with a more elaborate method in the literature, by presenting our results on the computer search for inhibitors of the HIV-1 protease. PMID- 1517777 TI - PLS modelling of structure-activity relationships of catechol O-methyltransferase inhibitors. AB - Quantitative structure-activity analysis was carried out for in vitro inhibition of rat brain soluble catechol O-methyltransferase by a series (N = 99) of 1,5 substituted-3,4-dihydroxybenzenes using computational chemistry and multivariate PLS modelling of data sets. The molecular structural descriptors (N = 19) associated with the electronics of the catecholic ring and sizes of substituents were derived theoretically. For the whole set of molecules two separate PLS models have to be used. A PLS model with two significant (crossvalidated) model dimensions describing 82.2% of the variance in inhibition activity data was capable of predicting all molecules except those having the largest R1 substituent or having a large R5 substituent compared to the NO2 group. The other PLS model with three significant (crossvalidated) model dimensions described 83.3% of the variance in inhibition activity data. This model could not handle compounds having a small R5 substituent, compared to the NO2 group, or the largest R1 substituent. The predictive capability of these PLS models was good. The models reveal that inhibition activity is nonlinearly related to the size of the R5 substituent. The analysis of the PLS models also shows that the binding affinity is greatly dependent on the electronic nature of both R1 and R5 substituents. The electron-withdrawing nature of the substituents enhances inhibition activity. In addition, the size of the R1 substituent and its lipophilicity are important in the binding of inhibitors. The size of the R1 substituent has an upper limit. On the other hand, ionized R1 substituents decrease inhibition activity. PMID- 1517776 TI - The sequence homologies of cytochromes P-450 and active-site geometries. AB - The amino acid sequence alignment of 16 cytochrome P-450 proteins representative of the major families is reported. The sequence matching process has been carried out on the basis of maximum homology by residue type, retention of secondary structure and minimization of deletions/insertions except where additional loop regions exist. From the starting point of known reported sequence homology matching from the literature, a realignment on the basis of conserved residues involved in both structure and function gives rise to a self-consistent set of sequences which correlates with known mechanistic and structural data. Once fitted, these archetypal sequences form a straightforward template for the alignment of all P-450 subfamilies. Computer modelling of the active-site regions constructed from homology with the bacterial form of the enzyme (P-450CAM) evinces the correct substrate specificity. Furthermore, the construction of the macromolecular assembly of components of the cytochrome P-450 system on the microsomal endoplasmic reticular membrane is presented from the evidence of site directed mutagenesis, analysis by molecular probes, X-ray crystallography and molecular modelling. PMID- 1517778 TI - Charge calculations in molecular mechanics. IX. A general parameterisation of the scheme for saturated halogen, oxygen and nitrogen compounds. AB - The CHARGE2 program for the calculation of partial atomic charges has been amended to include bond parameters for a number of organic functional groups, including halogens, nitrogen and oxygen. These minor amendments to the original scheme produce dipole moments for the fluoro and chloro compounds which are in complete agreement with the observed values. The less complete data sets for the bromo and iodo compounds are also well reproduced, and the dipole moments of a variety of mixed halo compounds are now in better agreement with experiment than previously. The calculated dipole moments of the saturated nitrogen and oxygen compounds are now in much better agreement than in the original scheme, thus the revised parameterisation may be employed with confidence to predict the electrostatic energies of these compounds. Furthermore, the revised scheme now gives a precise proportionality between the charge on the proton in a CH group and the 1H chemical shift of the corresponding proton, allowing the general prediction, in principle, of 1H chemical shifts. In addition, attempts to include variable electronegativity in the alpha effect are described for fluoro compounds. PMID- 1517779 TI - Conformational studies on (+)-anatoxin-a and derivatives. AB - Anatoxin-a (AnTX) is a highly potent agonist acting at the nicotinic acetylcholine receptor (nAChR) and represents a valuable tool in the study of this receptor. Molecular mechanics, semi-empirical and ab initio molecular orbital energy minimization procedures were conducted to investigate the conformation of AnTX. For each minimization procedure, the s-trans enone isomer of protonated AnTX was the energetically favoured conformer due to intramolecular electrostatic interactions. Our studies are discussed in the light of previous experimental observations and conformational studies, in addition to their importance in the development of future pharmacophore models for nAChR agonist binding. PMID- 1517780 TI - Radiosurgery: a new application? PMID- 1517781 TI - Whole-brain irradiation and decline in intelligence: the influence of dose and age on IQ score. AB - PURPOSE: Decline in intelligence can occur after whole-brain cranial irradiation for childhood malignancy. The purpose of this analysis was to estimate better the impact of dose and age at time of irradiation on IQ decline. PATIENTS AND METHODS: A total of 48 children were studied. We combined two previously reported studies that included 15 patients with pediatric acute lymphocytic leukemia (ALL) and 18 pediatric patients with medulloblastoma/posterior fossa primitive neural ectodermal tumors (PNETs) in whom serial IQ tests were administered. Another 15 patients (nine ALL and six PNET) were studied subsequent to these reports. This experience included ALL patients who were treated with whole-brain irradiation at doses of 18 Gy (n = 9) and 24 Gy (n = 15), and PNET patients who were treated with 18 Gy (n = 5), 22 to 24 Gy (n = 2), and 32 to 40 Gy (n = 17). Multiple regression models were constructed to estimate expected IQ score after treatment based on initial IQ score, age at treatment, and dose of whole-brain irradiation. RESULTS: Using a multiple linear regression model to correct for initial IQ and age at treatment, patients who received a dose of 36 Gy to the whole brain were estimated to score 8.2 points less on IQ testing than those with 24 Gy (95% confidence interval [CI], 1.8 to 14.6) and 12.3 points less than those who received 18 Gy (95% CI, 2.7 to 21.7). Older age at the time of irradiation resulted in less decline in subsequent IQ score. The predicted IQ decline is 11.9 points less in a 10-year-old patient than in a 3-year-old patient (95% CI, 4.2 to 19.6) for equivalent doses of irradiation. The model to predict IQ accounts for half the total variation in IQ score. There was no significant difference between the coefficients that reflected IQ decrease from radiation dose between subgroups who had ALL versus those with PNET. CONCLUSIONS: One can forecast final IQ score based on the initial IQ score, dose of irradiation, and age at time of irradiation. Our findings should aid in the selection of appropriate therapy when whole-brain irradiation is needed. PMID- 1517782 TI - Educational, occupational, and insurance status of childhood cancer survivors in their fourth and fifth decades of life. AB - PURPOSE: Survivors of childhood cancer who are now greater than or equal to 30 years of age are available for study in significant numbers for the first time. An evaluation of their educational achievement, current employment status, frequency of problems in the work-place, and ability to obtain affordable health and life insurance was the aim of this study. PATIENTS AND METHODS: This was a case-control study of 219 childhood cancer survivors with individually matched controls from two tertiary-care pediatric centers. Telephone interviews were used and drew on a 356-item basic instrument for both subjects and controls. Medical (including intensity of therapy), marital, and psychosocial areas were included in the survey, but statistical comparisons concentrated on educational and economic issues. RESULTS: The overall current status of survivors and controls in the relevant areas, ie, education, employment, and insurance, was similar. A history of employment discrimination for entry into the uniformed services and in other special situations, and life insurance discrimination during the initial years after the completion of therapy was noted. Survivors experienced few problems in the work-place. Survivors of CNS tumors were unique, with problems in many of the areas studied, although there were notable individual exceptions. CONCLUSION: With the exception of those individuals with CNS tumor histories, survivors who were treated in the era of 1945 to 1975 had few economic sequelae of cancer or its therapy that extended beyond the first decades after treatment. PMID- 1517783 TI - No benefit of ifosfamide in Ewing's sarcoma: a nonrandomized study of the French Society of Pediatric Oncology. AB - PURPOSE: To undertake a new protocol with the goals of improving the chemotherapeutic treatment of pediatric Ewing's sarcoma by introducing ifosfamide, and to widen the indications for surgical resection of Ewing's tumor to obtain better local control and to reduce radiation doses. PATIENTS AND METHODS: The French Society of Pediatric Oncology initiated its first cooperative Ewing's sarcoma study in 1978, using a four-drug regimen (cyclophosphamide, dactinomycin, Adriamycin [doxorubicin; Farmitalia Carlo Erba, Rueil-Malmaison, France], and vincristine). Ninety-five patients were included, and, at 5 years, the disease-free survival reached a plateau of 51%. After encouraging responses of recurrent soft tissue or bone sarcomas to ifosfamide, a second study began in 1984 using a new chemotherapy regimen in which cyclophosphamide was replaced by ifosfamide. Sixty-five patients were treated. RESULTS: By February 1992, the median follow-up was 5.8 years. The estimated 5-year disease-free survival was 52%. We observed unexpected cardiac toxicity. Three patients experienced acute cardiac failure that was lethal in two cases. The acute toxicity of ifosfamide prompted us to stop the protocol. Retrospectively, the lack of efficacy reinforced our decision. CONCLUSION: We conclude that ifosfamide did not improve the outcome of the patients despite the fact that these two treatment regimens were not randomized. PMID- 1517784 TI - Microgranular variant of acute promyelocytic leukemia in children. AB - PURPOSE: The microgranular variant (M3v) of acute promyelocytic leukemia (APL) rarely has been reported in a pediatric series of acute nonlymphoblastic leukemia (AnLL). We reviewed the clinical and biologic features of childhood M3v cases in our AnLL series. PATIENTS AND METHODS: From January 1970 to January 1991, 11 children with M3v were admitted and treated at our center. A diagnosis was made according to French-American-British (FAB) criteria. Morphologic examination, cytochemical analysis, and immunophenotyping were performed by a single pathologist. From January 1984, the diagnosis was confirmed by cytogenetic and, subsequently, by molecular analysis on frozen material. RESULTS: In our series, the overall incidence of children with APL was unusually high, 31.2% of the AnLL and M3v constituted one case in every four cases of APL. Even restriction of the analysis to the time when either cytogenetic and DNA studies confirmed the diagnosis, the incidence did not change. The immunophenotype of M3v cases was identical to that described for the hypergranular type, but an unexpected association of CD2 with M3v was shown. The onset was characterized by marked hyperleukocytosis (median WBC count, 87 x 10(9)/L) unlike classic APL. Disseminated intravascular coagulation (DIC) was always present and severe. Hyperleukocytosis and DIC were responsible for the high incidence of deaths for hemorrhagic events in the first days after onset (eight of 11 patients). CONCLUSIONS: In our experience, for unknown reasons, M3v may occur in childhood more than generally was considered. The clinical course and prognosis seem worse in M3v than in typical APL cases. PMID- 1517785 TI - Expression of myeloid-associated and lymphoid-associated cell-surface antigens in acute myeloid leukemia of childhood: a Pediatric Oncology Group study. AB - PURPOSE: Although the expression of both myeloid- and lymphoid-associated cell surface antigens in acute myeloid leukemia (AML) has been described, the clinical significance of such antigen expression remains unknown in the pediatric population. We sought to define an antibody panel for optimal diagnostic antigenic analysis and to test associations among antigen expression and a number of clinical features at presentation and prognosis in pediatric AML. PATIENTS AND METHODS: We reviewed the extensive immunophenotypic analysis performed at the time of diagnosis on 132 assessable patients registered on a single Pediatric Oncology Group AML protocol between 1984 and 1988. RESULTS: Eighty-eight percent of patients were identified by testing for expression of CD33 and CD13. Overall, 61% of patients expressed at least one lymphoid-associated antigen, most commonly CD4, CD7, or CD19. Expression of CD5, CD10, CD20, or CD22, commonly detected in T or B-lineage pediatric acute lymphoid leukemia (ALL), was uncommon; coexpression of multiple lymphoid-associated antigens was also uncommon. Expression of the monocyte-associated antigen CD14 correlated with French-American-British (FAB) M4 or M5 morphology. Otherwise, no correlation between antigen expression and FAB classification was noted. None of the myeloid, lymphoid, natural-killer (NK), or progenitor-associated antigens were associated with significant differences in the likelihood of remission induction or event-free survival when expressor versus nonexpressor groups were compared. CONCLUSIONS: The distribution of cell surface antigen expression in pediatric acute leukemia usually permitted the discrimination of AML from ALL by using a limited panel of antibodies. Although the expression of lymphoid-associated antigens was common, such expression did not seem to be associated with an adverse prognosis in pediatric AML. PMID- 1517786 TI - Therapy-related acute promyelocytic leukemia: a report on 16 cases. AB - PURPOSE: To analyze the type of prior tumor and treatment in therapy-related acute promyelocytic leukemia (tAPL) that occurs after chemotherapy and/or radiotherapy (RT), and the hematologic characteristics and outcome of tAPL. PATIENTS AND METHODS: Sixteen patients with tAPL who were gathered during a 10 year period (1982 to 1991) in seven hematologic centers were analyzed retrospectively. RESULTS: There were 13 women and three men. The median age was 46 years (range, 12 to 82). Prior tumor was breast carcinoma in 10 cases, another solid tumor in three cases, and lymphoma in three cases. Two patients had received RT alone, and 14 had received chemotherapy (with RT in 11 cases). Prior chemotherapeutic agents generally included a combination of cyclophosphamide (used for limited periods), fluorouracil (5-FU), vinca alkaloids, and doxorubicin, mitoxantrone, or etoposide (VP16). By contrast, alkylating agents other than cyclophosphamide had been used in only two patients. Median interval between onset of treatment for the prior tumor and diagnosis of APL was 25 months. No patient had a known preleukemic phase. Hematologic and cytogenetic characteristics of the cases of tAPL were identical to those of the usual de novo APL, which included the presence of t(15; 17) in nine of the 10 patients tested. Two patients had early death. Seven patients were treated with intensive chemotherapy, and six achieved complete remission (CR). Three of them subsequently relapsed. Seven patients were treated with all-trans-retinoic acid (ATRA), and four achieved CR through the differentiation of blasts into mature granulocytes. None has relapsed so far. CONCLUSIONS: Our findings suggest that tAPL is not exceptional, and usually has several features in common with other types of therapy-related AML with specific karyotype (ie, t(8;21),t(9;11), inv(16)): solid tumor rather than hematologic malignancy as primary tumor, short interval of development, absence of known preleukemic phase, prior chemotherapy with a combination of several drugs that often included an agent that targets topoisomerase II (doxorubicin or mitoxantrone, but less often VP16). Hematologic characteristics and response to therapy (intensive chemotherapy or ATRA) in tAPL do not seem to differ from those of de novo APL. PMID- 1517787 TI - Acute monocytic or myelomonocytic leukemia with balanced chromosome translocations to band 11q23 after therapy with 4-epi-doxorubicin and cisplatin or cyclophosphamide for breast cancer. AB - PURPOSE: To report five cases of acute monocytic or myelomonocytic leukemia after chemotherapy with 4-epidoxorubicin for breast cancer and to evaluate the risk of leukemia after the use of this drug. PATIENTS AND METHODS: One hundred fifty seven patients with advanced breast cancer were randomized to either 4-epi doxorubicin plus cisplatin or 4-epi-doxorubicin alone. An additional 203 patients were treated prospectively with 4-epi-doxorubicin alone. All were observed closely for leukemic complications. RESULTS: Three patients from the randomized study developed leukemia; all were in the subgroup of 74 patients who received 4 epi-doxorubicin plus cisplatin, whereas no leukemia was observed among the remaining 83 patients in the randomized study or among the additional 203 patients who were treated prospectively with 4-epi-doxorubicin alone (P = .023, log-rank test). In the subgroup of 74 patients who were treated with 4-epi doxorubicin plus cisplatin, the cumulative risk of leukemia was 16.0% +/- 9.9% (mean +/- SE) 33 months after the start of therapy; the relative risk was 668 (95% confidence interval [Cl], 138 to 1,953). Two other cases of acute monocytic and myelomonocytic leukemia were observed after 4-epi-doxorubicin plus alkylating agents were administered for breast cancer. Three of five cases of leukemia presented balanced translocations to chromosome band 11q23 and two, loss of a whole chromosome no. 7 or its long arm. CONCLUSIONS: 4-epi-doxorubicin is leukemogenic, and the leukemias are often acute monocytic or myelomonocytic with balanced chromosome translocations to band 11q23, such as in the leukemias after therapy with the epipodophyllotoxins. Furthermore, our results suggest a synergistic effect in leukemogenesis between 4-epi-doxorubicin targeting DNA topoisomerase II and directly genotoxic drugs such as cisplatin or alkylating agents. PMID- 1517788 TI - Sequential administration of interleukin-3 and granulocyte-macrophage colony stimulating factor following standard-dose combination chemotherapy with etoposide, ifosfamide, and cisplatin. AB - PURPOSE: To combine the benefits of recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF) on neutrophil recovery and recombinant human interleukin-3 (rhIL-3) on platelet recovery, we applied standard-dose chemotherapy with the combined administration of IL-3 and GM-CSF to investigate their efficacy and toxicity. PATIENTS AND METHODS: Thirty-six patients with advanced malignancies were treated with etoposide (VP16) 500 mg/m2, ifosfamide 4 g/m2, and cisplatin 50 mg/m2 (VIP), followed by the sequential administration of IL-3 (days 1 to 5 subcutaneously [SC]) and GM-CSF (day 6 to 15 SC). Control patients received GM-CSF alone or were treated without hematopoietic growth factors. RESULTS: Subcutaneous IL-3 and GM-CSF treatment was well tolerated; low grade fever (World Health Organization grade 1 to 2) was the only consistent clinical symptom. Neutrophil recovery documented that the duration of neutropenia less than 0.1 x 10(9)/L or less than 0.5 x 10(9)/L was identical in GM-CSF as well as IL-3 and GM-CSF-treated patients, but was shortened significantly when compared with patients who were treated without cytokines. Overall platelet recovery was not different significantly in the three treatment groups. The biologic activity of IL-3 in this cytokine combination was reflected in a variety of effects, which included an increase in basophil and eosinophil counts and the induction of circulating hematopoietic progenitor cells. CONCLUSION: We conclude that after conventional-dose VIP chemotherapy, a shortened treatment course of IL 3 (5 days) sequentially followed by GM-CSF (10 days) combines the benefits of prolonged single GM-CSF treatment on WBC count recovery in all patients and an accelerated platelet recovery only in some intensively pretreated patients. PMID- 1517789 TI - Dosing regimen of granulocyte-macrophage colony-stimulating factor to support dose-intensive chemotherapy. AB - PURPOSE: This trial evaluated the optimum dosing regimen for recombinant human granulocyte-macrophage colony-stimulating factor (rhu GM-CSF) to support a dose intensive chemotherapy regimen given without progenitor cell replacement. PATIENTS AND METHODS: Fifty-one patients with refractory malignancy received cyclophosphamide 2,500 mg/m2 on days 1 and 2, etoposide 500 mg/m2 on days 1, 2, and 3, and cisplatin 50 mg/m2 on days 1, 2, and 3. Patients were hospitalized from cycle days 1 to 4 for chemotherapy and readmitted for cytopenic temperatures above 38.5 degrees C. Cycles were repeated every 35 days in patients who responded to a total of three cycles. GM-CSF was given at doses of 250 to 1,000 micrograms/m2 by continuous intravenous infusion (CIV) or subcutaneously starting on cycle days 3 to 6. Two nonrandomized control groups are used. RESULTS: The optimum regimen of GM-CSF for shortening the duration of leukopenia (WBC count less than 300/microL) was 500 micrograms/m2 given CIV. Duration of leukopenia was 5.9 days compared with 13.2 and 10.2 days in the controls (P less than .05). The optimum regimens for shortening duration of hospitalization, however, were 500 and 750 micrograms/m2/d given as divided (twice daily) subcutaneous injections. Durations of hospitalization were 9.6 and 9.8 days compared with 15.7 and 22.2 days in the controls (P less than .08). At the higher GM-CSF dose, only 36% of patients required readmission for cytopenic fever. Toxicities of GM-CSF at clinically useful doses were minimal. Twelve patients had complete response (24%) and 22 partial response (43%). CONCLUSIONS: This dose-intensive regimen can be given safely without progenitor replacement. rhu GM-CSF decreases the duration of severe leukopenia and decreases the need for hospitalization and antibiotic therapy. PMID- 1517791 TI - Impact on survival of surgically defined favorable responses to salvage intraperitoneal chemotherapy in small-volume residual ovarian cancer. AB - PURPOSE: To evaluate the impact on survival of the attainment of surgically defined favorable responses (S-R) to salvage intraperitoneal (IP) chemotherapy after initial systemic cytotoxic drug delivery. PATIENTS AND METHODS: We examined the survival of patients who were treated on one of three phase II IP trials that were conducted at the Memorial Sloan-Kettering Cancer Center. A total of 58 patients whose largest residual tumor masses measured less than or equal to 0.5 cm in maximum diameter at the initiation of this salvage therapy were assessable for response, 28 of whom (48%) demonstrated a S-R, which included 19 (33%) who achieved a surgically defined complete response (S-CR). RESULTS: With a median follow-up of 43+ months (range, 33+ to 58+ months) from the initiation of IP therapy, 12 of 19 (63%) have recurred. The median duration of S-CR for the 10 patients with microscopic residual disease was 32 months compared with 15 months for the nine patients with macroscopic residual disease (largest tumor mass less than or equal to 0.5 cm; P greater than .1). For patients with microscopic residual disease who experienced a S-CR (n = 10) after salvage IP therapy, the median overall survival from the initiation of therapy has not been reached, but will exceed 4 years compared with a 25-month median survival for the nonresponding patients (n = 13; P = .004). The median survival for the 18 patients with small-volume macroscopic disease who responded to therapy was 40 months compared with 19 months for the nonresponders (P = .009). CONCLUSION: Although the results of this evaluation are encouraging and suggest that the attainment of a S-R, particularly a S-CR, after IP chemotherapy may result in a clinically meaningful favorable impact on survival, a randomized controlled trial will be required to address definitively this important issue. PMID- 1517790 TI - Phase I trial of murine monoclonal antibody L6 in combination with subcutaneous interleukin-2 in patients with advanced carcinoma of the breast, colorectum, and lung. AB - PURPOSE: A phase I trial was undertaken to determine the toxicity and biologic effects of a combination of murine monoclonal antibody L6 (MoAb L6) plus subcutaneous (SC) interleukin-2 (IL-2). PATIENTS AND METHODS: Fifteen patients with refractory adenocarcinoma (five breast, five lung, five colorectal), received L6 at 200 mg/m2 intravenously (IV) daily on days 1 to 7, followed by a 1 week rest period. IL-2 was given at either 2, 3, or 4.5 x 10(6) U/m2 daily doses times 4 days for a total duration of 3 weeks. RESULTS: Side effects of L6 consisted of mild fever and chills along with a rash and serum sickness in one patient. One patient developed dyspnea and urticaria, that resolved with antihistamines. Maximum-tolerated dose (MTD) of SC IL-2 was 3 x 10(6) U/m2, with dose-limiting toxicities that consisted of grade 4 fatigue and dyspnea. Significant decreases in complement levels along with increases in absolute lymphocyte count and eosinophil count were observed. Mean antibody-dependent cellular cytotoxicity from mononuclear cells taken from patients who received IL 2 was elevated significantly compared with baseline in all patients independent of IL-2 dose (P less than .05). Serum IL-2 levels were elevated in 13 of 14 patients (range, 0.9 to 100 U/mL). Human antimouse antibody (HAMA) titers were elevated in nine of 14 (64%) patients who were tested between 3 and 8 weeks after L6 infusion. One patient with breast cancer had a transient mixed response, and one patient with colorectal cancer had a partial response. CONCLUSIONS: L6 and SC IL-2 were well tolerated in the majority of patients when given in the outpatient setting. In view of the clinical efficacy of this combination, more phase II trials are warranted. PMID- 1517792 TI - Phase I study of busulfan and cyclophosphamide in preparation for allogeneic marrow transplant for patients with multiple myeloma. AB - PURPOSE: To study the toxicity and potential efficacy of busulfan (BU) and cyclophosphamide (CY) as a conditioning regimen before allogeneic bone marrow transplantation (ABMT) in patients with multiple myeloma (MM). PATIENTS AND METHODS: Twenty patients with MM underwent conditioning, which was followed by ABMT from 16 HLA-identical donors, three one-antigen-mismatched donors, and one HLA A, B, D-identical unrelated donor. Four levels of BU plus CY were evaluated. RESULTS: Severe regimen-related toxicity occurred in two of five patients who received BU 16 mg/kg and CY 120 mg/kg, in none of the four patients who received BU 14 mg/kg and CY 120 mg/kg, in one of eight patients who received BU 14 mg/kg and CY 147 mg/kg, and in two of three patients who received BU 14 mg/kg and CY 174 mg/kg. Twelve of 15 (80%) assessable patients achieved a complete remission with the disappearance of M-protein and the return of normal marrow morphology. Ten patients died of complications related to the ABMT, and two patients died of progressive or relapsed MM. Overall, eight of 20 patients were alive; seven (35%) were in complete remission 190 to 1,271 days after ABMT. CONCLUSIONS: The maximum tolerable dose given in this setting was BU 14 mg/kg and CY 147 kg/mg. These results suggest that this regimen may have significant antimyeloma activity. Further phase II studies are warranted. PMID- 1517793 TI - Why oncologists burnout. PMID- 1517794 TI - Cisplatin overdosage. PMID- 1517795 TI - Neuropsychologic and neurologic side effects of mitotane and reversibility of symptoms. PMID- 1517796 TI - The cytotoxic action of lymphokine activated killer cells upon the human glioma cell line U251 is stimulated by bispecific monoclonal antibody (MoAb) constructs. AB - The ability of IL-2 stimulated mononuclear cells to kill the human glioblastoma cell line U251 has been investigated. Highest cytotoxic activity was generated in low cell density cultures incubated for 15 days with 250-1000 U/ml IL-2. Sub optimal killing was noted, with cells only exposed to IL-2 for three days. Under the latter conditions, bispecific monoclonal antibodies (MoAbs) of either anti CD3 or anti-CD16 and an anti-NCAM MoAb stimulated LAK cell activity markedly. Anti-CD16 conjugates were found more effective than anti-CD3 and (Fab')2 constructs more efficacious than those made with whole Ig molecules. Maximal stimulation of LAK cell activity was noted with bispecific MoAbs. Little effect was observed with either single or mixtures of monomeric MoAbs. Furthermore, no effect of bispecific MoAbs was observed when target cells lacked expression of NCAM. These results could be of clinical importance as it is not always feasible to screen LAK cells for optimal activity before administration to patients. Whilst bispecific MoAbs have no effect on optimally stimulated LAK cells, they are not inhibitory and can stimulate killing under sub-optimal IL-2 stimulation. PMID- 1517797 TI - Pharmacology of intrathecal VP-16-213 in dogs. AB - VP-16-213 is an anticancer drug that is active against a number of malignancies including small cell lung cancer, lymphoma, and leukemia which are often complicated by the development of leptomeningeal carcinomatosis. To investigate the potential usefulness of VP-16-213 for intrathecal administration, the pharmacology and toxicity of intrathecal VP-16-213 was determined. VP-16-213 at varying doses (0.01-1.0 mg.kg) was instilled intrathecally in dogs. Plasma, CSF, spinal cord, and brain tissue drug concentrations were determined by radiochemical and high performance liquid chromatography technique. Drug concentrations were strikingly higher in spinal cord tissue near the injection site compared to more distal cord sites. CSF concentration of VP-16-213 is 3-4 logs higher compared to concurrent plasma levels. Severe neurotoxicity occurred at the higher doses used. Due to limited diffusion and extremely low doses which could be used without life-threatening neurotoxicity, VP-16-213 does not appear to be a useful agent for intrathecal administration. PMID- 1517798 TI - Fluorescent dye rhodamine 6G as a molecular probe to study drug resistance of C6 rat glioma cells. AB - A study was made of the membrane transport of cytoplasm and mitochondria stained fluorescence dye Rhodamine 6G (R6G). In rat glioma C6 cells and 1-(4-amino-2 methyl-5-pyrymidinyl)-methyl-3-(2-chloroethyl) -3-nitrosourea hydrochloride (ACNU) and vincristine (VCR) resistant cell lines (C6/ACNU, C6/VCR), the rate of uptake of R6G decreased in C6/VCR cells, but verapamil increased the intracellular accumulation of R6G in C6/VCR. The intracellular accumulation of R6G of C6/ACNU cells was essentially the same as that of wild-type cells. C6/ACNU cells did not show cross resistance and were sensitive to VCR and cisplatin. C6/VCR cells showed cross resistance to ACNU and CDDP, but C6/VCR cells in the presence of verapamil were more sensitive to drugs than C6/VCR cells in the absence of verapamil. We conclude that the reduction of R6G fluorescence staining intensity in C6/VCR cells compared to wild-type cells may be associated with the mechanism of multidrug resistance (MDR) but does not reflect the mechanism of resistance to ACNU. Verapamil increased the accumulation of R6G in C6/VCR cells and overcame MDR, suggesting that there is a correlation between the MDR overcoming effect and enhancement of R6G accumulation, and that this correlation validates the use of the R6G staining test for clinical and laboratory investigation of MDR. PMID- 1517799 TI - Histologic factors in the grading and prognosis of astrocytoma grade I-IV. AB - The prognostic value of histologic or cytologic features were examined in 317 patients with an astrocytic glioma. Of 46 features examined 7 morphologic characteristics of nucleus and 5 of mesenchyma correlated well with grading according to Kernohan. The morphological characteristics of nucleus are cellularity, atypical nuclei, polymorphism, multinucleated cells, hyperchromasia, gigantic nuclei and mitosis. For mesenchyma these were vascularity, vascular endothelial proliferation, vascular glomeruli, necrosis with palisade formation and necrosis without palisade formation. Scoring of these items on a scale from 0 to 4 enables us to establish a nucleus-score (max. 28) and a mesenchyma-score (max. 20). Nucleus-score + mesenchyma-score less than or equal to 10 corresponds with astrocytoma grade II, less than or equal to 20 with grade III and greater than 20 with grade IV. A low nucleus-score in grade II (less than 5) predicts a long survival (greater than 10 years), a high nucleus-score a low survival (median 0.6 year). In grade III a low mesenchyma-score predicts a median survival of 1.25 years, a high mesenchyma-score a median survival of 0.38 year. This retrospective study shows that nucleus-score and mesenchyma-score correlate to grading according to Kernohan and are highly correlative to survival. PMID- 1517800 TI - Comparison of myelography combined with postmyelographic spinal CT and MRI in suspected metastatic disease of the spinal canal. AB - Comparison between myelography (MY) and magnetic resonance imaging (MRI) was carried out in 36 patients with clinical suspicion of spinal cord or root compression due to metastatic disease in the spinal canal. In 3 patients metastatic lesions were visualized on MY but not on MRI, while there were no cases with a negative MY and a positive MRI. In 44% of the cases MY alone or combined with postmyelographic CT (pm-CT) showed a larger tumor extension than did MRI, while the opposite occurred in 25%. As for detection of bony metastases and tumor masses localized outside the spine there was no difference between MRI and MY + pm-CT. The results indicate that the choice between MRI and MY + pm-CT still can be based on the availability and quality of the procedure at a given institution. PMID- 1517801 TI - Intraventricular neurocytoma: four cases report. AB - Intraventricular neurocytoma, a newly identified disease entity with probably not so rare incidence, has several distinctive clinico-pathological characteristics. Four cases are presented. As in the other cases reported in the literature [1-7], the characteristic features are young age, location close to the junction of the septum pellucidum and foramen of Monro, and well-differentiated neuronal origin pathologically. PMID- 1517803 TI - Prolonged remission of primary central nervous system lymphoma after discontinuation of steroid therapy. AB - The case of a 63-year old man is presented in whom remission of a primary central nervous system lymphoma was achieved by corticosteroids only. After discontinuation of steroid therapy the remission persisted for two and a half years. Recurrences appeared at other sites of the brain, and were steroid resistant. PMID- 1517802 TI - The recurrence of primary intracranial germinomas. Special reference to germinoma with STGC (syncytiotrophoblastic giant cell). AB - Twenty three cases of primary intracranial germinomas including five cases of germinomas with syncytiotrophoblastic giant cells are studied and analyzed, with special reference to the recurrence under radiotherapy. The follow-up period for all cases was 7 months to 12 years (average: 5.8 years) with that for pure germinomas ranging from 8 months to 12 years (average: 5.7 years) and that for germinomas with syncytiotrophoblastic giant cells ranging from 7 months to 11 years (average: 6.3 years). Late recurrence was observed in three cases (3/23, 13%), developing outside of the initial irradiation field. With regard to recurrence, significant correlation to radiation fields was evident, while it was not to radiation doses. Furthermore, germinoma with syncytiotrophoblastic giant cells showed a more significant tendency to recur than pure germinoma. The radiotherapy of germinomas is discussed and the clinical features of germinoma with syncytiotrophoblastic giant cells are presented. PMID- 1517805 TI - Effect of intra-arterial cisplatin and 1,3-bis(2chloroethyl)-1-nitrosourea (BCNU) dosage on radiographic response and regional toxicity in malignant glioma patients: proposal of a new method of intra-arterial dosage calculation. AB - The frequency of both neurologic toxicity and therapeutic response due to intra arterial (IA) chemotherapy is decreased by dose reduction. A method to individualize IA drug dosage is needed to provide each patient with the safest, most effective dose. Most trials of IA chemotherapy for malignant glioma have used body surface area (BSA) to calculate dosage; but brain size and arterial distribution do not correlate well with BSA. Fixed doses of cisplatin and BCNU were used in combination to perform 35 IA infusions in 20 malignant gliomas patients. Doses modified by the number of major intracranial vessels supplied by the infused artery were used in 34 infusions in 19 patients. Patients receiving 150 to 200 mg CP and 300 mg BCNU had an incidence of neurologic deficit of 5.6% if greater than or equal to 3 vessels were supplied by the infused artery compared to 42% for those with only 2 vessels. This crude dose modification maintained efficacy while reducing neurologic toxicity. Further refinement is possible using well established intra-arterial pharmacokinetic principles. Intra arterial dosing based on volume flow at the site of infusion would yield a more reproducible exposure of the infused capillary bed to a drug than methods currently in use. More consistent drug exposure should reduce toxicity due to over dosing and treatment failure due to under dosing. PMID- 1517804 TI - Intracranial ependymoma in children: analysis of prognostic factors. AB - Between 1955 and 1986, 25 children (aged 2 weeks to 15 years) were treated for intracranial ependymoma at M.D. Anderson Cancer Center. Nine patients had supratentorial primaries (5 high-grade, 4 low-grade), and 16 had infratentorial primaries (9 high-grade, 7 low-grade). Five patients had gross complete resection and 20 had incomplete resection. Seven patients received craniospinal irradiation (25-36 Gy to the neuro-axis, 45-55 Gy to tumor bed), 12 received local field irradiation (29-60 Gy, median 50 Gy). Five infants had adjuvant chemotherapy without radiotherapy, and 6 children had post-radiotherapy adjuvant chemotherapy, and 12 patients had salvage chemotherapy with various agents and number of courses. Eight patients are alive, disease-free and without relapse from 1 year to 12 1/2 years from diagnosis (median 42 months). The primary failure pattern was local recurrence. The data suggest that 1) the long-term cure rate of children with ependymoma is suboptimal; 2) histologic grade may be of prognostic importance for supratentorial tumors; 3) prognosis appears worse for girls and infants under 3 years of age; 4) in well-staged patients routine spinal irradiation could be omitted; 5) the role of adjuvant chemotherapy is unclear. PMID- 1517806 TI - Parameters characterizing the in vitro activity of cefixime, a new oral broad spectrum cephalosporin, against respiratory and urinary pathogens. AB - The wide and potent in vitro activity of cefixime, a new oral broad spectrum cephalosporin, has been confirmed on a collection of respiratory and urinary pathogens recently isolated in Italy. The new cephem emerged as the most bactericidal of all the comparators tested against several fast as well as slowly growing gram-negative species including Enterobacteria, Haemophilus and Moraxella, irrespective of their ability to synthetize beta-lactamases. Among the gram-positive species Streptococcus pyogenes and S. pneumoniae were effectively covered. Cefixime activity was not adversely influenced by several important variables such as pH (over the range from 5 to 8), inoculum size (from 10(5) to 10(8) CFU per ml) and the presence of 50% human serum or urine. Time-kill tests confirmed a pronounced bactericidal potency of the drug especially towards common respiratory pathogens (H. influenzae, M. catarrhalis, S. pneumoniae and S. pyogenes). Killing of urinary strains was optimal at cefixime concentrations reached in urine since eradication, except for Proteus mirabilis, was enhanced with increasing levels of the drug. The absence of an untoward paradoxic effect on the rate of cefixime bactericidal action was confirmed by employing a dynamic bladder model simulating the pharmacokinetic parameters of the drug after a single 200 mg daily dosage. Interactions of cefixime with several other drugs that may be employed in combination therapy were generally prone to provide indifference and synergism while antagonism was never observed. Favorable interactions were also registered when cefixime acted with other antibiotics on partially resistant species such as Staphylococci and Pseudomonas. The new cephem seems to provide excellent opportunities for expanding oral cephalosporin therapy to a wide range of infections produced by susceptible pathogens in the adult and pediatric populations. PMID- 1517807 TI - Study on the influence of adsorbent substances against the antigen activity of inactivated orovaccines. AB - Specific IgAGM, IgA and IgG levels were evaluated in two groups of rabbits orally treated with inactivated vaccine consisting of Escherichia coli, Proteus vulgaris, Staphylococcus aureus and Streptococcus faecalis and with the same vaccine supplemented with charcoal and kaolin, respectively. The determinations demonstrated that charcoal and kaolin do not have a significant, negative effect on immunoresponses at the intestinal and hematic level after both medium (two week) and prolonged (four-week) treatment. PMID- 1517808 TI - Pharmacokinetic study of cefaclor in chronic maxillary sinusitis. AB - The pharmacokinetics of the maxillary sinus fluid were studied in 42 patients (26 males and 16 females), suffering from chronic maxillary sinusitis, after oral administration of 0.5g or 1g cefaclor. A thin plastic catheter, for sinus secretion sampling, was inserted in the sinus cavity and remained in place throughout the study. Sinus fluid levels of cefaclor (0.5g), measured by agar and well-diffusion microbiological method, ranged between 0.17-0.19, 0.28-0.42, 0.18 0.22 and 0.12-0.16 microgram/ml at 2, 4, 6 and 8 hour intervals respectively. Levels ranging between 0.15-0.26, 0.37-0.90, 0.23-0.27 and 0.16-0.19 microgram/ml were found after the administration of 1g cefaclor at the same time intervals respectively. Higher levels were found in purulent nasal material than in cystic fluid aspirates. PMID- 1517809 TI - Epidemiology and therapy of Chlamydia trachomatis genital infection in women. AB - Out of 1172 females recruited in a screening program for genital infections, 144 (12.28%) were cervical and/or urethral positive for Chlamydia trachomatis (Ct) by enzyme immunoassay (EIA). Patients positive for Ct showed no significant differences in terms of demography, sexual practices and clinical evidence as compared to a control group formed by Ct-negative females randomly selected. Historical data showed a higher frequency of previous pelvic inflammatory disease (PID) in patients as compared to controls. 11 of the 94 patients' partners tested were sperm positive for Ct. Of the 63 patients for whom therapeutic data were available, 38 were treated with josamycin, 16 with tetracycline and the others with different drugs. After treatment, EIA for Ct was negative for 92.1% of the patients treated with josamycin and for 68.7% of those treated with tetracycline. The results of this study confirm a high prevalence of asymptomatic Ct infection which may be correctly diagnosed by EIA performed on cervical and urethral samples. They also indicate that negative test results can be obtained by an appropriate antibiotic treatment. PMID- 1517811 TI - Cost-effectiveness comparison of single and multiple-dose antibiotic treatment of lower uncomplicated urinary tract infections. AB - This study analyzed the cost-effectiveness of antibiotic treatments of different durations for acute cystitis in non-pregnant females. Questionnaires were sent to 400 practitioners evenly distributed throughout Italy. Data are reported from 2,069 patients. The clinical bacteriological efficacy at 10-15 days was 86.4% for single-dose treatment with fosfomycin-trometamol (FT), and 81.8% for the multiple dose antibiotics group (MDAG). Disappearance of symptoms occurred in 2.1 days with FT and 3.4 days with MDAG. With FT 93.8% of patients were free of adverse events and 86.9% with MDAG. Analysis of the cost-effectiveness indicators for cure rate and absence of adverse events showed that treatment costs were similar for all antibiotics. FT needed less time interval for symptoms to disappear with a slightly higher cost than for MDAG, which had a better cost/effectiveness ratio. PMID- 1517810 TI - Evaluation of aztreonam in the treatment of serious gram-negative infections in a university hospital in Saudi Arabia. AB - The efficacy and safety of aztreonam were evaluated in an open trial at King Khalid University Hospital, Riyadh, Saudi Arabia. A total of 45 critically-ill adult patients were enrolled in the study. All patients with documented Gram negative infection were treated with aztreonam as monotherapy. Antibiotics active against only Gram-positive and/or anaerobic organisms were allowed. Twenty cases were clinically evaluable. Eleven had lower respiratory tract infections (pneumonia), 3 had urinary tract infections, and 6 had septicemia. Clinical signs and symptoms, cultures and other laboratory profiles were assessed prior to treatment, at 4-6 days during treatment and within 2-3 days of the end of therapy (usually 7-15 days). Nineteen out of 20 (95%) had a satisfactory clinical response. All cases with septicemia and urinary tract infections were microbiologically cured. The overall microbiological response rate was 90%. Fifty five percent of all infections were caused by Pseudomonas aeruginosa. Two patients with Gram-negative pneumonia due to P. aeruginosa did not respond microbiologically to aztreonam therapy. No serious adverse events requiring discontinuation of aztreonam therapy were reported. No mortality occurred. PMID- 1517812 TI - Influence of radiotherapy on intestinal microflora in cancer patients. AB - We investigated in 15 patients with carcinoma of the uterine cervix or endometrium, who were undergoing postoperative radiation therapy, the effects of different fractionated radiation exposures on counts of fecal bacteria, on the growth of Clostridium difficile and Clostridium perfringens enterotoxin production. We observed a generally significant decrease in intestinal microflora after the first radiation exposure, whereas at the end of radiotherapy all bacteria increased and reached basal values except Enterococcus faecium 1, lactobacilli and total anaerobes. In some patients we observed an overgrowth of some Clostridium spp. which were potential pathogens associated with clinical symptoms. We did not observe an influence of multiple radiations on C. perfringens enterotoxin fecal contents. We conclude that patients receiving radiotherapy may benefit from the intake of oral bacteriotherapy, i.e. live beneficial bacteria such as Bacillus subtilis at the beginning of the irradiation exposure. PMID- 1517813 TI - Carboplatin and radiation therapy for stage IV carcinoma of the head and neck. Preliminary results of a phase II study. AB - 34 patients with head and neck cancer were treated with carboplatin and radiation therapy. Eligibility criteria included stage IV biopsy-proven squamous cell carcinoma with measurable disease and no distant metastases, Karnofsky performance status score of 60 or greater, age 18 years or more, no previous radiation therapy and adequate hematological, renal, and hepatic function. There were 27 males and 7 females. Ages ranged from 44-70 years with a median of 57 years. Follow-up ranged from 11-34 months with a median of 21 months. Total tumor doses ranged from 50-55 Gy with additional boosts of 15-20 Gy. Carboplatin was given in a dose of 100 mg/m2 once weekly (26 patients) and 200 mg/m2 once every 2 weeks (8 patients), during the radiation therapy course in all 34 patients. Each dose of carboplatin preceded irradiation. 25 patients responded while 9 did not. There were 19 complete responses (CR) and 6 partial responses. 4/19 CR recurred and 5/9 non-responding patients died of disease. Mild to moderate nausea and vomiting were seen in 52.3% of patients and mucositis was seen in 61.8% of patients. Moderate to severe hematological toxicity was seen in 35.3% of patients. Response rates and toxicity we observed during this study clearly show that the combination of carboplatin and radiation therapy is effective and suitable for the treatment of patients with stage IV head and neck cancer. PMID- 1517814 TI - Treatment of elderly advanced gastric cancer patients with 5-fluorouracil and leucovorin combination. AB - In September 1987 a phase II study was begun to verify if elderly symptomatic patients affected by advanced gastric cancer could benefit from a combination of 5-fluorouracil (5FU) and leucovorin (LV). We employed Machover's regimen: 5FU 370 mg/m2 i.v. infusion daily for 5 days; LV 200 mg/m2 i.v. bolus daily for 5 days; cycles were repeated every 3 weeks. 23 patients entered the study and 22 were evaluable for response and toxicity. We obtained only one partial response; 9 had stable disease and 12 progressed on therapy. The median duration of survival was 6 months. Symptoms were not affected by treatment. These data reflect the absence of significant improvement in the quality of life, which was further lessened by the presence of treatment side effects. Because of this we think that this regimen cannot be recommended for the treatment of elderly advanced gastric cancer patients. PMID- 1517815 TI - Effect of intra-arterial versus intravenous cisplatin in addition to systemic adriamycin and high-dose methotrexate on histologic tumor response of osteosarcoma of the extremities. AB - In neoadjuvant treatment of osteosarcoma of the extremities intra-arterial (IA) instead of intravenous (IV) administration of cisplatinum (CDDP) has been advocated to improve local response and consequently increase the percentage of limb salvages and the cure rate. Since the major local advantages from the IA use of CDDP have been recently questioned, a comparative prospective study was performed at the Rizzoli Institute between July 1990 and September 1991. Preoperative chemotherapy consisted of two cycles of high-dose methotrexate (HDMTX), followed 6 days later by CDDP and adriamycin (ADM), HDMTX and ADM were delivered intravenously while CDDP was delivered according to previous randomization, either intra-arterially or intravenously. Of the 79 patients who entered the study 40 received CDDP IA and 39 CDDP IV. The percentage of clinical and radiological response of the tumor as well as the percentage of limb salvage procedures performed was the same in the two groups. However the rate of good histological response (tumor necrosis greater than 90%) was significantly higher in the group of patients who received IA CDDP than in the patients who received the drug intravenously (77.5% vs 46%: p less than 0.01). No differences in terms of local or systemic side effects were found in the two groups. A longer follow up is necessary to establish if this improved good response rate achieved with IA CDDP will lead to an improved cure rate.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1517816 TI - Recruitment of motor units in human forearm extensors. AB - 1. Experiments were conducted on single motor units of two forearm muscles, extensor carpi radialis (ECR) and extensor digitorum communis (EDC) of human subjects. Our interest was whether or not task groups could be identified in these forearm muscles, and, if so, was there orderly recruitment within each task group. 2. To test for the presence of separate task groups within ECR, motor-unit recruitment was examined for two isometric contractions:wrist extension and radial deviation. Each of the ECR motor units tested repeatedly discharged during contractions in both directions, indicating the absence of separate task groups in ECR for contractions in these two directions. 3. Recruitment order between pairs of ECR motor-unit action potentials was examined for wrist extension and radial deviation. For 58 paired comparisons, the order of recruitment was the same in both directions. In terms of force output, plots of twitch torque versus recruitment threshold of ECR motor units showed a positive correlation for both directions, wrist extension and radial deviation, demonstrating size-ordered recruitment of ECR motoneurons for both contractions. 4. The EDC motoneuron pool exhibited two partially overlapping subpopulations of motoneurons on the basis of task, one subpopulation recruited for middle finger extension and the second one for ring finger extension. Contractions involving the index and little fingers were not examined. It is concluded that motor-unit task groups do exist within EDC motoneuron pool. Plots of twitch torque versus recruitment threshold showed positive correlations for each of these two task groups.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1517817 TI - PGO-related potentials in lumbar motoneurons during active sleep. AB - 1. The present report describes the relationship that occurs during active sleep between ponto-geniculo-occipital (PGO) waves and changes in spinal cord motoneuron membrane potential. 2. These changes were characterized by the appearance of a complex pattern of motoneuron hyperpolarizing potentials, with a duration of approximately 300 ms, that were centered around the PGO wave. The first hyperpolarizing potential began before the onset of the PGO wave. Emerging from this hyperpolarizing potential was a second, larger-amplitude hyperpolarizing potential; it was followed by a succession of smaller-amplitude hyperpolarizations. 3. All potentials were present in conjunction with PGO waves during active sleep, but they were observed only in some motoneurons when PGO waves occurred during the transition period from quiet sleep to active sleep. 4. The potentials were reversed by chloride, demonstrating that they were inhibitory postsynaptic potentials (IPSPs). 5. These data, combined with the fact that these PGO-related IPSPs are blocked by strychnine, support the hypothesis that they are the result of the phasic enhancement of the activity of the same system that inhibits motoneurons during active sleep. PMID- 1517818 TI - Isoproterenol enhances a calcium-independent potassium current in mouse anterior pituitary tumor cells. AB - 1. The patch-clamp technique was used to study the action of the beta-adrenergic agonist (-)-isoproterenol in anterior pituitary tumor cells of the mouse. 2. (-) Isoproterenol induced an inward-rectifying potassium conductance with half maximal stimulation at a concentration of approximately 67 nM. The isomer (+) isoproterenol was less effective in stimulating the current. 3. The effect of (-) isoproterenol was abolished by cholera toxin treatment, indicating the involvement of a Gs protein, whereas pertussis toxin treatment did not exhibit a current reduction. 4. We blocked or stimulated phosphorylation pathways in cells to test the involvement of adenosine 3',5'-cyclic monophosphate (cAMP). It was concluded that the current stimulation probably was not exclusively mediated by cAMP. 5. Activation of calcium-dependent potassium channels by an isoproterenol induced calcium influx into the cell could be excluded. 6. Therefore it is suggested that the observed activation of a potassium current by isoproterenol could be directly mediated by a Gs protein. PMID- 1517819 TI - Effects of OFF-BF tones on responses of chopper units in ventral cochlear nucleus. I. Regularity and temporal adaptation patterns. AB - 1. We have recorded the responses of neurons in the anteroventral cochlear nucleus (AVCN) of barbiturate-anesthetized cats to pure tones [either at the unit's best frequency (BF) or at another frequency (OFF-BF)] and to two-tone combination stimuli. 2. The effects of OFF-BF input (either alone or presented simultaneously with a BF tone in a two-tone stimulus) on the response patterns of choppers may include not only rate inhibition but changes in the discharge regularity and the temporal adaptation properties of the spike trains. 3. In the majority of cases we studied (119 of 146 frequencies examined in 45 units), the discharge regularity of a response to an OFF-BF or two-tone stimulus is comparable with that of a "rate-matched" BF tone response. In a minority of cases (27 of 146 frequencies examined), however, OFF-BF input (either alone or in a two tone stimulus format) changed the regularity compared with that of a rate-matched BF tone response. 4. In the majority of cases studied (139 of 171 frequencies examined in 53 units), the initial pattern of rate adaptation ["temporal adaptation pattern" (TAP)] was the same in response to a short tone burst at BF, to an OFF-BF tone burst, or to a pair of tones. The TAP can, however, be significantly altered by OFF-BF input, although this is a comparatively infrequent occurrence in our data sample (32 of 171 frequencies examined), from the response to BF tone to the response to the two-tone or OFF-BF stimulus, are as follows: sustained to slowly adapting; slowly adapting to transiently adapting, and transiently adapting to slowly adapting. Changes in the TAPs of chopper unit responses have been recorded from both regular and irregular choppers and cannot be accounted for on the basis of changes in sustained firing rate. These changes in the discharge regularity and TAP in the small minority of cases suggest that (at least in these cases) the inhibitory effect of OFF-BF input is not simply the result of two-tone suppression at the level of the auditory nerve fiber input. 5. We have observed that regular choppers may be transformed into irregular choppers by OFF-BF (rate inhibitory) input.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1517820 TI - Organization of suppression in receptive fields of neurons in cat visual cortex. AB - 1. The response to an optimally oriented stimulus of both simple and complex cells in the cat's striate visual cortex (area 17) can be suppressed by the superposition of an orthogonally oriented drifting grating. This effect is referred to as cross-orientation suppression. We have examined the spatial organization and tuning characteristics of this suppressive effect with the use of extracellular recording techniques. 2. For a total of 75 neurons, we have measured the size of each cell's excitatory receptive field by use of rectangular patches of drifting sinusoidal gratings presented at the optimal orientation and spatial frequency. The length and width of these grating patches are varied independently. Receptive-field length and width are determined from the dimensions of the smallest grating patch required to elicit a maximal response. 3. The extent of the area from which cross-orientation suppression originates has been measured in an analogous manner. Each neuron is excited by a patch of drifting grating the same size as the receptive field. The response to this stimulus is modulated by a superimposed patch of grating having an orthogonal orientation. After selecting the spatial frequency that produces maximal suppression, the response of each cell is examined as a function of the length and width of the orthogonal (suppressive) grating patch. Results from 29 cells show that the dimensions of the orthogonal grating patch required to elicit maximal suppression are similar to, or smaller than, the dimensions of the excitatory receptive field. Thus cross-orientation suppression originates from within the receptive field. 4. For some cells the spatial frequency tuning of the suppressive effect is much broader than the spatial frequency tuning for excitation. In these cases it is possible to find a spatial frequency that produces suppression but not excitation. With the use of a suppressive stimulus having this spatial frequency, we examined the strength of suppression as a function of orientation for 11 cells. These tests show that suppression occurs at all orientations, including the preferred orientation for excitation. In some cases, suppression is somewhat stronger at the preferred orientation for excitation than at any other orientation. 5. For 12 cells we varied the relative spatial phase between the optimally oriented and orthogonal gratings. In all cases the magnitude of suppression is largely independent of the relative spatial phase. 6. For three binocular cells we examined whether the suppressive effect of a grating oriented orthogonal to the optimum could be mediated dichoptically.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1517821 TI - Neural responses to visual texture patterns in middle temporal area of the macaque monkey. AB - 1. We studied how neurons in the middle temporal visual area (MT) of anesthetized macaque monkeys responded to textured and nontextured visual stimuli. Stimuli contained a central rectangular "figure" that was either uniform in luminance or consisted of an array of oriented line segments. The figure moved at constant velocity in one of four orthogonal directions. The region surrounding the figure was either uniform in luminance or contained a texture array (whose elements were identical or orthogonal in orientation to those of the figure), and it either was stationary or moved along with the figure. 2. A textured figure moving across a stationary textured background ("texture bar" stimulus) often elicited vigorous neural responses, but, on average, the responses to texture bars were significantly smaller than to solid (uniform luminance) bars. 3. Many cells showed direction selectivity that was similar for both texture bars and solid bars. However, on average, the direction selectivity measured when texture bars were used was significantly smaller than that for solid bars, and many cells lost significant direction selectivity altogether. The reduction in direction selectivity for texture bars generally reflected a combination of decreased responsiveness in the preferred direction and increased responsiveness in the null (opposite to preferred) direction. 4. Responses to a texture bar in the absence of a texture background ("texture bar alone") were very similar to the responses to solid bars both in the magnitude of response and in the degree of direction selectivity. Conversely, adding a static texture surround to a moving solid bar reduced direction selectivity on average without a reduction in response magnitude. These results indicate that the static surround is largely responsible for the differences in direction selectivity for texture bars versus solid bars. 5. In the majority of MT cells studied, responses to a moving texture bar were largely independent of whether the elements in the bar were of the same orientation as the background elements or of the orthogonal orientation. Thus, for the class of stimuli we used, orientation contrast does not markedly affect the responses of MT neurons to moving texture patterns. 6. The optimum figure length and the shapes of the length tuning curves determined with the use of solid bars and texture bars differed significantly in most of the cells examined. Thus neurons in MT are not simply selective for a particular figure shape independent of whatever cues are used to delineate the figure. PMID- 1517822 TI - Discharge patterns of levator palpebrae superioris motoneurons during vertical lid and eye movements in the monkey. AB - 1. We recorded single-unit activity in the caudal central nucleus (CCN) of the oculomotor complex in monkeys trained to make vertical saccadic, smooth-pursuit, and fixation eye movements. We confirmed that our recordings were from motoneurons innervating the upper lid, because small lesions placed at the sites of responsive units were recovered among neurons labeled by horseradish peroxidase (HRP) injections into the levator palpebrae superioris muscle. 2. For fixations above a threshold lid position, levator motoneurons discharged at a steady rate, which increased linearly with upward lid position. The average position sensitivity during fixation was 2.9 spikes/s per deg, and the average lid motoneuron was recruited into steady firing when the eye was looking 10 degrees down. 3. During upward saccades, levator motoneurons discharged a burst of spikes that began, on average, 7.3 ms before the lid movement if the saccade started from a straight-ahead position; the lead time decreased considerably as the initial eye and lid positions shifted downward. The firing rate usually reached its peak (130-280 spikes/s) at the very onset of the burst and declined gradually during the course of the saccade. The steady rate associated with the new fixation position was reached about halfway during the saccade. All units exhibited a pause in firing during the initial half of large downward saccades; during small saccades, the pause was inconspicuous or absent. 4. During vertical sinusoidal smooth pursuit, levator motoneurons exhibited a sinusoidal modulation in firing rate, which led eye position by an average of 23 degrees at 0.3 Hz. The average velocity sensitivity calculated from such data was 0.63 spikes/s per deg/s. 5. Although they exhibit a number of qualitative similarities, the discharge patterns of levator motoneurons and superior rectus motoneurons differ in several respects. First, during a blink, when the lid undergoes a large depression but the eye exhibits only a brief transient displacement, levator motoneurons cease firing completely, whereas superior rectus motoneurons continue to discharge. Second, for all types of coordinated lid and eye movements, levator motoneurons discharge at lower firing rates than do superior rectus motoneurons. Third, during saccades, levator motoneurons have less conspicuous and shorter lasting bursts and pauses than do motoneurons involved in rotating the eye. 6. During upward gaze, the qualitative similarity of their burst-tonic discharge patterns suggests that levator and superior rectus motoneurons receive input signals that originate from a common source, but that the signals are processed differently to deal with the different loads facing these muscles.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1517823 TI - Physiological and behavioral identification of vestibular nucleus neurons mediating the horizontal vestibuloocular reflex in trained rhesus monkeys. AB - 1. To describe in detail the secondary neurons of the horizontal vestibuloocular reflex (VOR), we recorded the extracellular activity of neurons in the rostral medial vestibular nucleus of alert, trained rhesus monkeys. On the basis of their activity during horizontal head and eye movements, neurons were divided into several different types. Position-vestibular-pause (PVP) units discharged in relation to head velocity, eye velocity, eye position, and ceased firing during some saccades. Eye and head velocity (EHV) units discharged in relation to eye velocity and head velocity in the same direction so that the two signals partially canceled during the VOR. Two cell types discharged in relation to eye position and velocity but not head velocity; other types discharged in relation to head velocity only. 2. The position in the neural path from the primary vestibular afferents to abducens motoneurons was examined for each type. Direct input from the vestibular nerve was indicated if the cell could be activated by shocks to the nerve at latencies less than or equal to 1.4 ms. A projection to abducens motoneurons was indicated if spike-triggered averaging of lateral rectus electromyographic (EMG) activity yielded responses with a sharp onset at monosynaptic latencies. 3. PVP neurons were the principal interneuron in the VOR "three-neuron arc." Eighty percent received primary afferent input, and 66% made excitatory connections with contralateral abducens motoneurons. Surprisingly few, approximately 11%, made inhibitory connections with ipsilateral abducens motoneurons. This imbalance in the ipsi- and contralateral projections was confirmed by measuring the EMG activity evoked by electrical microstimulation in regions where PVP neurons were located. 4. EHV neurons whose activity increased during contralaterally directed head or eye movements were also interneurons in the ipsilateral inhibitory pathway. Eighty-nine percent received ipsilateral primary afferent input, and 25% projected to ipsilateral abducens motoneurons. EHV neurons excited during ipsilateral movements received neither direct primary afferent input nor projected to either abducens nucleus. A small proportion of each of two other cell types having sensitivity to contralateral eye position made excitatory connections with contralateral abducens motoneurons. Other types rarely were activated from the eighth nerve or projected to the abducens nucleus. 5. The significance of the connections of VOR interneurons and the signals they convey is discussed for three situations: smooth pursuit of a moving target, suppression of the VOR, and the VOR itself. PVP neurons convey a signal with a ratio of eye position and velocity components that is inappropriate to drive motoneurons during pursuit or the VOR.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1517825 TI - Discharge patterns in nucleus prepositus hypoglossi and adjacent medial vestibular nucleus during horizontal eye movement in behaving macaques. AB - 1. Monkeys were trained to perform a variety of horizontal eye tracking tasks designed to reveal possible eye movement and vestibular sensitivities of neurons in the medulla. To test eye movement sensitivity, we required stationary monkeys to track a small spot that moved horizontally. To test vestibular sensitivity, we rotated the monkeys about a vertical axis and required them to fixate a target rotating with them to suppress the vestibuloocular reflex (VOR). 2. All of the 100 units described in our study were recorded from regions of the medulla that were prominently labeled after injections of horseradish peroxidase into the abducens nucleus. These regions include the nucleus prepositus hypoglossi (NPH), the medial vestibular nucleus (MVN), and their common border (the "marginal zone"). We report here the activities of three different types of neurons recorded in these regions. 3. Two types responded only during eye movements per se. Their firing rates increased with eye position; 86% had ipsilateral "on" directions. Almost three quarters (73%) of these medullary neurons exhibited a burst-tonic discharge pattern that is qualitatively similar to that of abducens motoneurons. There were, however, quantitative differences in that these medullary burst-position neurons were less sensitive to eye position than were abducens motoneurons and often did not pause completely for saccades in the off direction. The burst of medullary burst position neurons preceded the saccade by an average of 7.6 +/- 1.7 (SD) ms and, on average, lasted the duration of the saccade. The number of spikes in the burst was well correlated with saccade size. The second type of eye movement neuron displayed either no discernible burst or an inconsistent one for on-direction saccades and will be referred to as medullary position neurons. Neither the burst-position nor the position neurons responded when the animals suppressed the VOR; hence, they displayed no vestibular sensitivity. 4. The third type of neuron was sensitive to both eye movement and vestibular stimulation. These neurons increased their firing rates during horizontal head rotation and smooth pursuit eye movements in the same direction; most (76%) preferred ipsilateral head and eye movements. Their firing rates were approximately in phase with eye velocity during sinusoidal smooth pursuit and with head velocity during VOR suppression; on average, their eye velocity sensitivity was 50% greater than their vestibular sensitivity. Sixty percent of these eye/head velocity cells were also sensitive to eye position. 5. The NPH/MVN region contains many neurons that could provide an eye position signal to abducens neurons.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1517824 TI - Violations of Listing's law after large eye and head gaze shifts. AB - 1. Kinematic constraints were examined in static eye and head positions after large gaze shifts to visual targets. Three-dimensional eye and head rotations were measured in six adult human subjects by the use of the magnetic field search coil technique. 2. Eye positions in space were found to obey Donder's law; i.e., for any given gaze direction there was a unique three-dimensional orientation. In other words, angular eye positions in space (expressed as quaternions) were constrained to a two-dimensional surface. 3. When only the eye moved (head stationary), the shape of this surface resembled a plane and thus the eye position in space obeyed Listing's law. However, after gaze shifts involving both the eye and the head, the eye in space surface became twisted and thus nonplanar. This twist was similar to that achieved by a Fick gimbal model of rotations in which the horizontal axis is nested within a fixed vertical axis. During oblique gaze shifts, the head made predominantly horizontal movements whereas the eye made predominantly vertical movements. This, combined with the fact that the eye is mounted within the head, causes the eye in space surface to resemble that of a Fick gimbal. 4. The angular position of the head in space was also constrained to a two-dimensional surface. This surface was also not planar (Listinglike) and twisted in a manner similar to that of the eye in space. 5. Whereas the angular position of the eye in head was found to obey Listing's law after head-fixed gaze shifts, violations of Listing's law occurred after head-free gaze shifts. These violations showed significant intersubject variation in their magnitude and character. 6. Given that the eye in space violates Listing's law after head movements, the supposition that Listing's law serves the perceptual purpose of maintaining radial constancy is untenable. The Fick gimballike behavior of the head in space and eye in space may hold several advantages over a Listing's system. When the head in space behaves like a Fick gimbal, a horizontal line through the eyes remains parallel to the horizon. By having the eye in space behave like a Fick gimbal, the work done against gravity may be minimized by having the eye contribute more to vertical gaze shifts than does the head. PMID- 1517826 TI - PII component of the toad electroretinogram. AB - 1. The PII component of the electroretinogram (ERG) is comprised of the b-wave and the DC component and is thought to reflect bipolar cell activity. Although the b-wave is generated in large part by a K+/Muller cell mechanism, the origin of the DC component is unclear. In this paper we detail our investigation of the origin of the DC component. We hypothesize that the DC component is generated by a K+/Muller cell mechanism identical to that involved in b-wave generation. 2. We studied the ERG in the dark-adapted, isolated retina preparation of the toad, Bu fo marinus. We used K+ ion-sensitive microelectrodes (K+ISM), as well as conventional intra- and extracellular microelectrodes, to record [K+]o changes, the vitreal ERG, and Muller cell responses. 3. We used the excitatory amino acid receptor agonist N-methyl-DL-aspartate (NMDLA) to inhibit light responses of third-order neurons and thereby eliminate most of the ERG M-wave. In the absence of the M-wave, the ERG consisted of PII and PIII. We then superfused the retina with a solution containing both kynurenic acid (KYN) and 2-amino-4 phosphonobutyric acid (APB), which together inhibit all retinal responses proximal to the photoreceptors. In the presence of KYN and APB, the ERG consisted only of PIII. Using digital subtraction, we reconstructed PII. To our knowledge, this is the first report of the isolation of a PII component in the ERG of a nonmammalian species. 4. Using K+ISMs, we recorded the distal K+ changes in the outer plexiform layer (OPL).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1517827 TI - Serotonin-containing neurons in lobsters: their role as gain-setters in postural control mechanisms. AB - 1. The electrophysiological properties of two pairs of identified serotonin containing neurons in the fifth thoracic (T5) and first abdominal (A1) ganglia of the lobster, Homarus americanus, were studied with the use of intracellular recording methods. Intracellular dye injection combined with immunocytochemistry verified the neurochemical status of the recorded neurons. 2. The serotonin containing neurons usually are spontaneously active at 0.5-1.0 Hz and produce large, overshooting action potentials with a prominent after-hyperpolarization. The action potentials appear to be generated by a pacemaking mechanism endogenous to the cells. Extracellular recordings from thoracic connectives and from second thoracic roots show that action potentials from the cells in A1 and T5 are propagated rostrally along their axons and invade axon collaterals that innervate neurohemal organs in the second thoracic roots and the pericardial organs. These observations suggest that these serotonin-containing cells may function in part as important neurosecretory cells in the lobster. 3. Members of the pairs of serotonin-containing cells are not synaptically connected. They receive prominent inhibitory inputs in the form of inhibitory postsynaptic potentials (IPSPs), which exhibit discrete size classes and probably arise from several sources. Most IPSPs are temporally synchronized among the two pairs of serotonin-containing cells. 4. The serotonin-containing cells respond to stimulation of postural command fibers, with flexion command fibers exciting and extension command fibers inhibiting the cells, suggesting that these cells are a part of the postural flexion circuitry. 5. Intracellular activation or inhibition of the serotonin containing cells has no effect on the spontaneous readout of postural motor programs recorded from motor nerve roots. Coactivation of the serotonin containing cells and command fibers, or inhibition of the serotonin-containing cells while activating command fibers, however, shows that the cells act as "gain setters," modulating the interaction between command inputs and motoneuron outputs. 6. About 24% of the motor neuron units analyzed are influenced by the serotonin-containing cells. There is a bias toward facilitation of the readout of flexion motor programs, particularly with stimulation of strong and moderate flexion command fibers. 7. The serotonin-containing cells in T5 and A1 ganglia are hypothesized to serve two functions, one tonic and the other phasic, in modulating behavioral output in lobsters. Tonic firing of the cells should result in a sustained release of serotonin from central and peripheral sets of nerve terminals, which, in turn, could influence peripheral and central targets of the amine.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1517828 TI - Patch-clamp study of postnatal development of CA1 neurons in rat hippocampal slices: membrane excitability and K+ currents. AB - 1. The postnatal development of membrane properties and outward K+ currents in CA1 neurons in rat hippocampal slices was studied with the use of whole-cell patch-clamp techniques. 2. Neurons at all postnatal ages (2-30 days; P2-30) were capable of generating tetrodotoxin (TTX)-sensitive action potentials in response to intracellular injection of depolarizing current pulses. There was a gradual increase in the amplitude and a decrease in the duration of these action potentials with age. Stable values for spike duration were reached by P15, whereas spike amplitude increased until P20-25. In P2-5 neurons, the duration of action potentials was greatly prolonged by depolarization from the resting membrane potential, indicating a weak spike repolarizing mechanism at depolarized potentials. In contrast, the duration of spikes evoked in P20-30 neurons was not affected by similar changes in the membrane potential. 3. Application of tetraethylammonium (TEA, 10 mM) had no effect on the duration of spikes in P3-5 neurons, whereas application of 4-aminopyridine (4-AP, 2 mM) produced large increases in spike duration. In contrast, the duration of spikes in P26 neurons was greatly increased after TEA application, whereas 4-AP had smaller effects on spike duration in these neurons. 4. The input resistance and membrane time constant decreased with age from P2 to P15. The values for both parameters were considerably greater than those reported with conventional intracellular recording electrodes in the immature hippocampus. The resting membrane potential became more hyperpolarized with age. When the recording pipettes contained KCl (140 mM), the resting potential of P3-4 neurons was 34 mV depolarized compared with resting potentials observed with potassium gluconate-filled pipettes. Only a 13-mV change in resting potential was observed during similar comparisons in P27 28 neurons. 5. Outward currents activated by depolarization were examined with the use of voltage-clamp techniques in P2-30 neurons. In P2-5 cells, a small, slowly inactivating outward current was evoked with depolarizing commands from holding potentials near -50 mV. By preceding the depolarizing commands with a hyperpolarizing prepulse, an additional early transient outward current was evoked. The sustained and transient outward currents were separated by their kinetic properties and their sensitivity to cobalt (Co2+), TEA, and 4 AP.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1517829 TI - Time course of neural responses discriminating different views of the face and head. AB - 1. Measurements of the magnitude and time course of response were made from 44 cells responsive to static head views at different levels of stimulus effectiveness. In this way responses to complex stimulus patterns evoking good, poor, and midrange responses could be compared across the cell population. 2. Cells exhibiting both good and poor initial discrimination between head views were found at short and long latencies; there was no correlation of any of the temporal response parameters measured with cell response latency. 3. The time course of the population response to the most effective stimuli showed a rapid increase to a peak firing rate (onset to peak, rise time, 58 ms) that was on average 115 spikes/s above spontaneous activity (S/A), followed by slower decay (decay time, 93 ms) to a maintained discharge rate (15% of the peak rate above S/A). 4. Discrimination between responses to different head views exhibited by the population showed a sharp rise and reached highly significant levels within 25 ms after the population's response onset. 5. On average, activity in a single neuron (the Average Cell) rises to 44% of its peak response rate within 5 ms of the response onset. 6. The Average Cell also showed exceptionally fast discrimination between views, significant within 5 ms of response onset. 7. It is argued that the fast rise in firing rate, followed by a decay to a lower rate and the very fast emergence of discrimination are features of pattern processing present in real neural systems that are lacking in many processing models based on artificial networks of neuronlike elements, particularly those where discrimination relies on top-down and/or lateral competitive inhibition. 8. It is concluded that the only way to account for the rapid discrimination is to consider a coding system in which the first spike from multiple sources is used to transmit information between stages of processing. PMID- 1517830 TI - Bone scintigraphy following intravenous pamidronate for Paget's disease of bone. AB - Pamidronate is one of several powerful bisphosphonates able to produce prolonged remissions of Paget's disease. This study examined to what extent bone scan changes parallel the clinical response and whether there is variability in the behavior of individual lesions. Twenty-five patients with pagetic bone pain for more than 2 yr were examined with bone scintigraphy before and on average 8 mo after six 30-mg infusions of pamidronate given weekly. Serum alkaline phosphatase and urinary hydroxyproline-to-creatinine ratios were measured before and 6 mo after treatment. A second course of pamidronate was given to 13 patients who had clinical or biochemical relapse. Of 136 pagetic lesions, 13 (10%) completely resolved, 90 (65%) improved and 33 (24%) remained unchanged. There was no significant difference in response between bony sites, although less active lesions were more likely to resolve completely. In conclusion pamidronate has a powerful effect on bone scan appearances in Paget's disease. Most lesions improve but complete resolution is uncommon. Less active lesions are more likely to resolve and are less likely to require further therapy. PMID- 1517831 TI - Gallium imaging in metastatic and recurrent soft-tissue sarcoma. AB - Fifty-six patients with metastatic or recurrent soft-tissue sarcoma were evaluated by 67Ga-citrate imaging. Prior to entry on the therapy protocol, 52/56 (93%) patients had true-positive 67Ga studies. Two of four patients with liposarcoma, one of twelve with leiomyosarcoma and one with an epithelioid sarcoma had false-negative studies; 89/105 disease sites (85%) were 67Ga positive, including 100% of pleural lesions, 94% in bone, 88% in the abdomen, 85% in soft tissue, 78% in lung parenchyma and 56% of liver metastases. There was significant association between 67Ga avidity and tumor grade with the exception of mesothelioma. No relationship was seen between 67Ga avidity and tumor cell type, disease site or lesion size. Following therapy, 67Ga correctly identified 11/12 sites of active disease in 8/9 patients. Mean pre- and post-therapy 67Ga avidity scores did not differ significantly. Gallium-67 appears to have an important role in the evaluation of patients presenting with either primary or metastatic soft-tissue sarcoma. PMID- 1517832 TI - Significance of increased lung thallium uptake during adenosine thallium-201 scintigraphy. AB - To determine the relationship of lung 201Tl activity during adenosine scintigraphy to the presence and extent of coronary artery disease, we investigated 132 subjects comprising 4 groups: 36 normal volunteers, 19 patients with angiographically normal coronaries, 29 patients with single-vessel (greater than 50% luminal stenosis) and 48 patients with multivessel coronary artery disease. Lung activity was quantified relative to maximal myocardial activity in both an early anterior planar image (pretomography) and the unprocessed tomographic image in the anterior projection. A good correlation was found for the lung-to-heart ratio assessed by planar and tomographic imaging (r = 0.83, p less than 0.0001), but the ratio was higher with planar imaging. The lung-to heart ratio in the planar images was significantly higher in patients with multivessel disease compared to those with single-vessel disease (p less than 0.05) or volunteers and subjects with normal coronary arteries combined (p less than 0.001). A lung-to-heart ratio of greater than 0.45 in the planar images (upper 95% confidence limit for the normal subjects) was found in 6 (21%) single vessel disease and 17 (35%) multivessel disease patients. Patients with elevated lung thallium activity during adenosine infusion had more hypoperfused myocardial segments (p = 0.007), more segments with redistribution (p = 0.04) and larger initial perfusion defect size (p = 0.04) than those with normal lung activity. Thus, evaluation of lung activity during adenosine thallium scintigraphy provides supplementary information regarding the severity of coronary artery disease and extent of myocardial hypoperfusion. PMID- 1517833 TI - Bone mineral density of the axial skeleton in acromegaly. AB - Acromegaly is characterized by growth hormone (GH) hypersecretion and insulin like growth factor-I (IGF-I) excess, both of which stimulate osteoblast proliferation. At diagnosis, GH excess has usually been present for years. Furthermore, impaired gonadotropin secretion with hypogonadism is frequent. To date, studies of changes in bone mineral density (BMD) in acromegaly have been limited and the available data inconsistent. To investigate the effects of GH excess on proximal femur and lumbar spine BMD, a case series of 25 patients with acromegaly (8 eugonadal, 17 hypogonadal) documented by high plasma GH and IGF-I concentrations was studied. BMD was measured using dual-photon absorptiometry, hormonal and biochemical measurements, which included GH, IGF-I, serum calcium, phosphate, alkaline phosphatase, 1,25 dihydroxy vitamin D and urinary calcium and hydroxyproline excretion. Seven patients were re-studied after IGF-I was suppressed for six months by the somatostatin analog 201-995 (five patients) or pituitary adenomectomy (two patients). BMD was normal in 22 patients and was decreased at one site each in one eugonadal and two hypogonadal patients. BMD was similar between the eugonadal and hypogonadal groups at all sites. Urinary hydroxyproline excretion was equally increased in both groups. There was no correlation between any of the hormonal or biochemical parameters and the age, sex, race and body mass index matched Z-scores of BMD at any site. Following normalization of IGF-I for 6 mo in seven patients, there was no significant change of BMD. We conclude that proximal femoral and lumbar spine BMD is normal in most patients with active acromegaly, including those who are hypogonad. Successful treatment of acromegaly does not result in major short-term changes in BMD. PMID- 1517834 TI - Dosimetry and biodistribution of an iodine-123-labeled somatostatin analog in patients with neuroendocrine tumors. AB - A modified method for the preparation of a radiolabeled analog of somatostatin (123I-octreotide) is described. The pharmacokinetics and dosimetry of this analog were evaluated in patients with neuroendocrine tumors. Thirty patients had multiple blood and urine samples and sequential anterior and posterior whole-body scintigraphy up to 40 hr postinjection of 123I-octreotide. Region of interest analysis of the whole-body images was used to determine organ and tumor doses. The 123I-octreotide was rapidly cleared from the blood with a T 1/2 of 10 min by the hepatobiliary system. By 40 hr, approximately 55% was eliminated in the feces. The gallbladder wall received the highest dose (0.48 rad/mCi), with other organs receiving doses of 0.12 rad/mCi or less. Tumors were identified in 25 of 28 satisfactory studies. Tumor doses ranged from 0.1 to 0.6 rad/mCi. Calculations with 131I instead of 123I indicated that the gallbladder wall would receive 2 rad/mCi, while average tumor doses would range from 0.9 to 5.0 rad/mCi. Iodine 123-octreotide is a useful agent for the visualization of neuroendocrine tumors. The rapid washout of this agent from tumors precludes the possibility of radiotherapy with 131I-octreotide in these patients. PMID- 1517835 TI - Unilateral voluntary hand movement and regional cerebral uptake of technetium-99m exametazime in human control subjects. AB - The study examines the sensitivity of a region of interest approach to detect functional changes in brain metabolism with SPECT and split-dose 99mTc exametazime by replicating a simple hand movement experiment previously carried out with PET. Regional uptake of 99mTc-exametazime was determined in 12 healthy controls before and during a thumb-digit opposition task. Analysis of regional uptake was carried out blind to the hand used in the opposition task and showed a significant unilateral activation effect in a pericentral region of interest with opposite results in left- and right-handed activation. The maximum contralateral increase in tracer uptake was 16% before and 26% after correction for back diffusion. This is in good agreement with previous results employing absolute cerebral blood flow determination with PET and confirms the usefulness of 99mTc exametazime SPECT for the examination of functional metabolic changes. PMID- 1517836 TI - Semiquantitative assessment of myocardial blood flow and viability using polar map displays of cardiac PET images. AB - Preserved glucose metabolism in ischemically injured, dysfunctional myocardial tissue as demonstrated on PET imaging predicts functional improvement after revascularization. To characterize more precisely the relationship between regional myocardial blood flow, viability and extent and severity of flow and metabolism abnormalities, we developed a PC-based semiquantitative analysis technique using 13N-ammonia and 18F-deoxyglucose polar map displays. A data base for mean values (m) and standard deviations (s.d.) for relative 13N activities reflecting regional myocardial blood flow, relative 18F activities normalized to normal flow regions reflecting regional glucose utilization and the difference of normalized 18F and 13N activities as an index of a flow-metabolism mismatch was established in 11 normals. Parametric polar maps were derived by comparing patient data to a normal range defined as greater than m - 2 s.d. for relative myocardial blood flow and less than m + 2 s.d. for both relative glucose utilization and the difference between normalized 18F and 13N activities. Semiquantitative indices of extent and severity of blood flow defects, of relative increases in glucose utilization and of flow-metabolism mismatch areas are generated for the entire myocardium and the three coronary territories. The approach promises to be clinically useful to confirm presence and absence of flow and metabolic abnormalities and to assess their extent as a potential predictor of functional outcome after therapy. PMID- 1517837 TI - Crossed cerebellar hypoperfusion in unilateral major cerebral artery occlusive disorders. AB - We evaluated regional blood flow and oxygen metabolism in the cerebral and cerebellar cortices of 15 patients with unilateral major cerebral artery occlusive disorders with PET. These patients showed a cortical blood flow asymmetry in middle cerebral artery distribution. Only subcortical abnormalities were detected on computed tomography. Nine patients showed crossed cerebellar hypoperfusion, a reduction in contralateral cerebellar blood flow, while six did not. No difference in the degree of cerebral blood flow asymmetry existed between the two patient groups. However, oxygen metabolism asymmetry was more pronounced and was more closely matched to blood flow asymmetry in patients with crossed cerebellar hypoperfusion. These findings suggest that a major cause of cerebral cortical blood flow reduction is reduced metabolic demand in patients with crossed cerebellar hypoperfusion. Crossed cerebellar hypoperfusion may have clinical significance as a reflection of the cerebral metabolic state on blood flow images. PMID- 1517838 TI - Radionuclide cardiac volumes: effects of region of interest selection and correction for Compton scatter using a buildup factor. AB - The effects of region of interest (ROI) selection and correction for Compton scattered photons using a buildup factor on radionuclide left ventricular volumes calculated by the Links method were compared in 19 humans with contrast ventriculography and in phantoms. Three different methods of ROI selection were compared: a manual ROI, a second derivative ROI and a 50% count-threshold ROI. In phantoms without Compton scatter correction, volumes were overestimated by 30% (manual ROI), 20% (derivative ROI) and 1% (count threshold ROI). In subjects, results without Compton scatter correction were similar with overestimates of 50% (manual ROI) and 20% (derivative ROI) and an underestimate by 3% (count threshold method). Correction for Compton-scattered photons with the use of a phantom derived buildup factor resulted in improved accuracy for the manual ROI (+15%) and the derivative ROI (0%). A 50% count threshold ROI following interpolative background subtraction allows the accurate calculation of cardiac volumes without the need for scatter correction, while a second derivative ROI method requires a correction for Compton scatter with the use of a buildup factor. PMID- 1517840 TI - Radiation dosimetry for indium-111-labeled anti-CEA-F(ab')2 fragments evaluated from tissue distribution in rats. AB - Accurate dosimetric investigations are important to be able to fulfill the ambition of radiation protection in nuclear medicine and to minimize the radiation burden to the patient. This paper presents human radiation absorbed dose estimates following an administration of an 111In-labeled anti-CEA-F(ab')2 (BW431/31) based on detailed biodistribution and elimination data in a rat model. Animals were followed from the time of injection up to 28 days after injection. A significant initial uptake of 111In in the bone marrow, 25% of injected activity, was evident after 6 hr. The kidneys showed a maximal uptake of 20% at 24 hr. At the end of the study, 27% of the activity was still retained in the whole body. The estimated humans absorbed dose to the kidneys, testes, spleen and bone marrow was 2.27, 0.80, 0.51 and 0.37 mGy MBq-1, respectively. The effective dose was estimated to 0.27 mSv MBq-1. The tissue distribution in rats was comparable to that in humans, which was confirmed by whole-body scintigrams and human biopsies. PMID- 1517839 TI - Dose fractionation of radiolabeled antibodies in patients with metastatic colon cancer. AB - Twelve patients with metastatic colon cancer were treated with 131I-chimeric B72.3 (IgG-4) at total doses of 28 or 36 mCi/m2 in two or three weekly fractions. Bone marrow suppression was the only significant side effect. The degree of bone marrow suppression adjusted for whole-body dose was modestly but statistically significantly (p = 0.04) less than that seen with identical doses given as a single infusion for the total dose of 36 mCi/m2. Nine of twelve patients developed an antibody response to ch B72.3, which altered the kinetics of radiolabeled antibody in four patients given a second course of therapy. One patient had a minor response that lasted 4 mo. Fractionation of this particular radiolabeled antibody at the dose schedule used produced a modest increase in the therapeutic window in regard to administered dose. PMID- 1517841 TI - The effects of regional pulmonary blood flow on protein flux measurements with PET. AB - We used PET to evaluate whether changes in regional pulmonary blood flow (PBF) or plasma volume (PV) affect calculations of the pulmonary transcapillary escape rate (PTCER) for 68Ga-labeled transferrin. We reduced PBF in five dogs by inflating a right atrial balloon. Regional PBF decreased 25% to 174 +/- 40 ml/min/100 ml lung without a change in PV or PTCER. In eight other dogs, we decreased PBF and PV via controlled arterial hemorrhage. PBF decreased 45% to 110 +/- 33 ml/min/100 ml lung and PV decreased 22% without a change in PTCER. We also used a series of computer simulations to evaluate the effect of even greater reductions in regional PBF on PTCER calculations. These simulations showed, in support of the experimental data, that if PBF was greater than 40 ml/min/100 ml lung, PTCER could be accurately measured. However, below this level, PV was increasingly under-estimated and PTCER overestimated. The results indicate the sensitivity of the PTCER calculation to errors in the PV measurement, especially in regions of markedly reduced regional PBF. PMID- 1517842 TI - Use of the left ventricular time-activity curve as a noninvasive input function in dynamic oxygen-15-water positron emission tomography. AB - Noninvasive recording of arterial input functions using regions of interest (ROIs) in the left ventricular (LV) chamber obviates the need for arterial cannulation in PET, but it is compromised by the limited recovery coefficient of the LV chamber and by statistical noise. In the present study, a new mathematical model has been developed, which corrects for the spillover of radioactivity both from the myocardium into the LV ROI and the blood into the myocardial ROI. The method requires the measurement of a time-activity curve in the LV chamber during the dynamic H2(15)O PET study and the measurement of the recovery coefficient of the LV ROI using a 15O-carbon monoxide (C15O) scan and venous blood sampling. This approach was successfully validated against direct measurements of the arterial input function using an on-line beta detector in five greyhounds undergoing dynamic H2(15)O PET imaging. This technique also yielded myocardial blood flow (MBF) values which were not significantly different from those obtained with the beta-probe analyses (maximum difference less than 2%), provided that the LV ROIs were sufficiently large to provide good counting statistics. When this model was not applied for large ROIs (small recovery in LV ROI), systematic overestimations in MBF compared with beta-probe analysis (e.g., a factor by 40% for a recovery coefficient of 0.7) were observed. Thus, this technique enabled the prediction of an accurate input function using the LV time activity curve, and hence, noninvasive quantification of MBF without arterial cannulation. PMID- 1517843 TI - Clinically important characteristics of maximum-likelihood reconstruction. AB - SPECT images of a Jaszczak rod phantom, a single-slice Hoffman brain phantom and a uniform water-bath were acquired. Simulated noisy bar phantoms incorporating depth-dependent attenuation and blur were produced and compared to simulations with depth-independent attenuation and blur, as is the case in PET. Following iterative maximum-likelihood reconstruction, regularization was performed with use of Gaussian filters. While correction for attenuation is achieved in approximately 10 iterations, spatial resolution in the SPECT reconstructions, quantified by contrast in the bar simulations and by visual inspection of the real data, was highly nonuniform, being poorest at the center and improving toward the periphery. Image resolution continued to improve well beyond 50 iterations when regularization was applied that maintained a constant signal-to noise ratio. Contrast in the simulated PET data also improved with increasing iterations, but the PET data showed uniform contrast throughout the transaxial slices at all numbers of iterations. PMID- 1517844 TI - Copper-64-labeled antibodies for PET imaging. AB - In the imaging of tumors using radiolabeled monoclonal antibodies, the use of PET gives increased sensitivity over conventional gamma camera imaging techniques. Copper-64, a positron-emitting radionuclide, has been labeled to 1A3, an anticolorectal carcinoma monoclonal antibody, and its fragments 1A3-F(ab')2 utilizing the bifunctional chelate Br-benzyl-TETA. The 64Cu-labeled intact 1A3 and 1A3-F(ab')2 have been evaluated as potential imaging agents for PET. Biodistribution studies of 64Cu-benzyl-TETA-1A3 and 64Cu-benzyl-TETA-1A3-F(ab')2 in tumor-bearing hamsters were compared with those of 111In-Br phi HBED-1A3, 111In-Br phi HBED-1A3-F(ab')2 and 125I-labeled intact 1A3 and 1A3-F(ab')2. Tumor uptake of 64Cu-labeled intact 1A3 and fragments in the hamster model was superior to both 111In- and 125I-labeled intact 1A3 and fragments. Human dosimetry data for 64Cu- and 123I-labeled 1A3 and 1A3-F(ab')2 were calculated from biodistribution data in rats. High kidney uptake of 64Cu-benzyl-TETA-1A3-F(ab')2 precludes clinical study at this time; however, the data shows that 64Cu-benzyl TETA-1A3 would be suitable for positron tomography imaging of colorectal cancer in patients. PMID- 1517845 TI - SPECT, magnetic resonance and angiographic features in a moyamoya patient before and after external-to-internal carotid artery bypass. AB - Brain SPECT changes in a patient with cerebral vaso-occlusive disease caused by moyamoya disease are presented. Brain SPECT after a revascularization procedure demonstrated significant improvement of brain flow which was confirmed by angiography. Clinical and magnetic resonance features are reviewed. PMID- 1517846 TI - Cerebral blood flow and glucose metabolism measurements in a patient surviving one year after carbon monoxide intoxication. AB - A 29-yr-old woman was studied for 1 yr after acute carbon monoxide intoxication following an attempted suicide by inhalation of automobile exhaust fumes. The patient demonstrated impaired responsiveness to stimuli without any specific neurological deficits for 1 yr after carbon monoxide intoxication. Repeated brain magnetic resonance imaging consistently displayed only bilateral globus pallidus lesions, but no lesions in either deep white matter or cerebral cortex. Position emission tomography measurements of regional cerebral blood flow, and glucose utilization rate were made in this patient at 6 mo and 1 yr following carbon monoxide intoxication. Impairment of both blood flow and glucose metabolism were found not only in the basal ganglia but also in morphologically normal frontal cortex. The decrease in glucose utilization in the frontal cortex was greater than that in the basal ganglia. During the period of 6 mo to 1 yr, blood flow and glucose metabolism in the basal ganglia recovered to the normal range. In the frontal cortex, however, blood flow and glucose metabolism remained approximately 20% lower than the normal mean values. This prolonged dysfunction in the frontal cortex may therefore be responsible for the impaired responsiveness of the subject. PMID- 1517847 TI - Stress fractures associated with osteosarcoma of the lower limb. AB - Three patients with osteosarcoma of the femur developed abnormal radiopharmaceutical uptake in the bones of the contralateral leg. This uptake was not due to metastases. The histology in one patient, the form of the lesion and the disappearance of the abnormal uptake without treatment in the other two, indicated that the uptake was probably due to stress fractures. Changes in weight bearing and walking in the normal leg as a result of the osteosarcoma in the other leg could have been the cause of the stress fractures. It should be recognized that new abnormal uptake on bone scintigraphy in patients with osteosarcoma of the leg may not necessarily indicate metastasis. It may be caused by a stress fracture and disappears after rest. PMID- 1517848 TI - Gallium-67 distribution in a man with a decrease in both transferrin and hepatic gallium-67 concentration. AB - A patient with reduced transferrin concentration had a 67Ga scintigram that showed uptake in a peritoneal abscess, pericarditis and pleural effusion but only faint liver uptake. Gallium-67 activity was measured in liver, lung, muscle and plasma samples obtained at autopsy. The percent injected dose/kg for liver and plasma samples was considerably lower than previously reported while that in muscle and lung tissues values were comparable to prior data. In this patient, sites on transferrin available to bind 67Ga were reduced from the normal 40 microM to 5.2 microM; this in turn increased the concentration of radiogallate from 1% to 7%. This elevated free activity increased 67Ga excretion and reduced the amount of 67Ga*transferrin species. These results and those of previous studies suggest that liver uptake is slower than abscess uptake and more sensitive to concentration of 67Ga*transferrin. Iron status is an important facet of the interpretation of 67Ga scintigrams. PMID- 1517849 TI - Necrotizing tracheobronchitis identified on an indium-111-white blood cell scan. AB - The clinical entity of necrotizing tracheobronchitis (NTB) is well described in the pediatric literature. The incidence of NTB in neonatal autopsies varies from 4% to 44%. More than 3 hr of assisted ventilation may be necessary for the development of NTB in neonates. A similar clinical problem was described as "hemorrhagic tracheitis" in two adults during high frequency jet ventilation and as a complication of conventional mechanical ventilation in an adult. We present here a rather unusual case of NTB in an adult on mechanical ventilation, in whom tracheobronchitis was diagnosed incidentally with an 111In white blood cell scan obtained for other purposes. PMID- 1517850 TI - The evaluation of the patient with gastroparesis secondary to insulin-dependent diabetes mellitus. PMID- 1517851 TI - Fast maximum-likelihood reconstruction. AB - A significant problem in application of maximum-likelihood reconstruction to SPECT and PET studies is the very long computation time required for this iterative algorithm. An approach is presented in which the basic calculations involved in projection and backprojection are performed only once and stored in computer memory, thus significantly reducing the computation time. PMID- 1517852 TI - The technetium-99m-DTPA renal uptake-plasma volume product: a quantitative estimation of glomerular filtration rate. AB - An image-based method for estimating quantitative renal glomerular filtration rates (GFR) by calculating the product of the renal uptake rate and plasma volume is presented. By using the relationship GFR = F.PV/t, F represents renal 99mTc DTPA uptake after bolus injection, PV is the plasma volume and t is time. This GFR evaluation was carried out on 96 patients and compared to GFR values determined in the same patients using radiotracer blood clearance techniques relying on two venous blood samples. When estimating patient plasma volumes using patient's weight and measured hematocrit values, the image-based method for calculating GFR accurately approximates the values obtained from blood samples (linear regression slope = 1.03; y-intercept = -2.81 ml/min). The two techniques correlate with a value of r = 0.89. PMID- 1517853 TI - MIRD dose estimate report no. 16: radiation absorbed dose from technetium-99m diethylenetriaminepentaacetic acid aerosol. PMID- 1517854 TI - Radiation injury after interstitial injection of iodocholesterol. PMID- 1517855 TI - Thallium stress test for ECG response and perfusion images. PMID- 1517856 TI - Quantitative dynamic parameters to evaluate impotence. PMID- 1517857 TI - Threatened reactor worker strike startles nuclear medicine profession. PMID- 1517858 TI - GAO probe details U.S. isotope trouble. PMID- 1517859 TI - Industry split over approval of PET tracers. PMID- 1517860 TI - Nursing's Agenda for Health Care Reform: a call to action. PMID- 1517861 TI - Orienting foreign nurse graduates through preceptors. AB - Many staff development departments have difficulty orienting foreign nurse graduates. Some of the difficulties foreign nurses themselves have are described in this article, as are difficulties American nurses have in orienting them. Nursing preceptors trained to understand and solve the problems of foreign nurse graduates may make orientation more successful for the nurse and the unit. PMID- 1517863 TI - Helping staff help students. AB - Nurses in a variety of health care settings work with nursing students. Staff development educators can help the nurses create a successful student affiliation while protecting the agency and patients. By teaching staff what to ask and what to tell, educators help students learn without compromising care. Positive student experiences also may help recruit new graduates to the agency. Teaching the staff to share information will help staff help students. PMID- 1517862 TI - Rejuvenating orientation to increase nurse satisfaction and retention. AB - The current nursing shortage has forced nursing managers to examine the reasons for nurse turnover and to evaluate institutional programs and policies that may strengthen staff nurse retention. For the past two decades, the nursing profession has concluded that nurse retention is linked to job satisfaction. Accordingly, employers have attempted to improve job satisfaction by permitting self-scheduling, nurse selection of unit assignment, and bonus pay for less desirable shifts. In spite of these and other efforts designed to retain nurses, the turnover rate generally has remained high. PMID- 1517864 TI - Using self-studies to meet JCAHO requirements. AB - Using self-studies to provide mandatory information for hospital employees is both cost effective and time effective. Time invested in writing and distributing these programs is well worth it provided learning is verified through testing. Records of mandatory information can be kept either by hand on education cards or by computer. Periodic updates of material keep the self-study process fresh and interesting for participants and educators alike. PMID- 1517865 TI - A systems approach to capillary blood glucose monitoring. A joint nursing/patient education effort. AB - Capillary blood glucose monitoring was successfully instituted on the nursing units at a small community hospital using a systematic, goal-directed process. Through the efforts of the diabetes educator and the coordinator of nursing education, nursing staff are now able to detect fluctuations in patient blood glucose levels rapidly and to provide prompt treatment. The system was implemented on the nursing units with preceptors serving as instructor-trainers. The implementation required the close cooperation and collaboration of multiple hospital departments. The nurse educator and the diabetes educator conduct ongoing monitoring using data collected from the patient, the nurse, and the multidisciplinary team. PMID- 1517866 TI - Investigating the effectiveness of self-learning packages in staff development. AB - The nursing shortage and high patient acuity levels make it difficult for nurses to attend traditional inservice programs. Time and financial constraints affect the staff educator's ability to teach needed topics to large numbers of nursing staff. This study suggests that the use of self-learning packages can be a viable alternative or adjunct to traditional inservice programs for nursing staff development. PMID- 1517867 TI - First steps toward peer review. PMID- 1517868 TI - Planning and implementing a housewide fall prevention program. PMID- 1517869 TI - Orienting yourself to a staff development role. PMID- 1517870 TI - Dentine hypersensitivity--the effect of toothbrushing and dietary compounds on dentine in vitro: an SEM study. AB - Dentine hypersensitivity occurs when dentinal tubules are open on the dentine surface and patent to a vital pulp. There has been limited interest in the aetiology of dentine hypersensitivity. In particular, little is known about agents that remove the dentine smear layer to expose tubules. Toothbrushing certainly may expose dentine, but whether a toothbrush per se has the effect of opening tubules has not been established. The aim of this study in vitro was to determine whether a toothbrush could remove or create a smear layer. In addition, the combined effects of toothbrushing with dietary fluids on dentine was assessed. Toothbrushing was observed, by scanning electron microscopy, both to remove and to recreate a smear layer on dentine specimens. However, the processes took a considerable time, and under conditions of normal toothbrushing it is unlikely that the latter plays a direct aetiological role in opening tubules. Indeed, together with toothpaste it is more likely that brushing has a therapeutic action by mechanically forming a smear layer. Conversely, and importantly, toothbrushing in the presence of dietary acids enhanced smear layer removal. This finding raises the question of whether the dental profession should be advising that teeth be brushed before meals rather than after, as is often the case. PMID- 1517871 TI - The antimicrobial effect of an iron-binding agent on Streptococcus mutans. AB - The antimicrobial activity of 2,2'-bipyridine, an iron-binding agent, was investigated by incorporating this agent into Scotchbond dental adhesive resin. The growth of Streptococcus mutans on the surface of resin, media and culture vessel was determined by optical density measurements. It was observed that 2,2' bipyridine exhibited excellent antimicrobial properties. PMID- 1517872 TI - Stresses generated by luting resins during cementation of composite and ceramic inlays. AB - The present study used the finite element method to model the stresses generated by a composite luting cement around a class I composite restoration and a ceramic inlay. In many cases maximum tensile stresses of greater than 20 MPa were found, and failure of the restoration-dentine and restoration-glass ionomer interfaces was predicted. PMID- 1517873 TI - Age and maintenance of removable dentures in Finland. AB - The age and maintenance of dentures, and denture-cleaning habits, were studied by an interview survey. The material represented nation-wide the Finnish population aged greater than or equal to 15 years old, and there were 957 interviewees, of whom 328 were denture wearers. In total, 45% of the upper and 40% of the lower dentures were over 10 years old. More than one-third of the dentures more than 5 years old had never been maintained during that time. Individuals whose dentures had been made and fitted by dental technicians visited dentists less frequently than individuals whose dentures had been made by dentists. Over 80% of the denture wearers reported cleaning their dentures by brushing at least once a day, and women cleaned them more frequently than men. The present findings suggest that denture wearers should be a special target group for dental health education, for the development of the latter, and for the development of dental health care services in the future. PMID- 1517874 TI - Surface electromyographic estimates of recruitment/rate coding of masseteric motor units. AB - Surface electromyographic (EMG) recordings were obtained from the masseter muscles in healthy subjects performing brisk maximum voluntary teeth clenching (MVC) for about 1 s. During the onset (0-600 ms) of ballistic MVC activity, the peak amplitude of the EMG interference patterns showed a consistent and significant increase, on examination for 0-200 ms, 200-400 ms, and 400-600 ms of MVC activity. The peak (maximum) and median (centroid) frequencies of power spectrum density functions of the raw surface EMGs (interference patterns) showed an absence of consistent and significant changes during 0-600 ms of ballistic MVC activity. However, the estimated total energy contents (peak amplitude x peak frequency) of the surface interference patterns showed a consistent and significant increase from 0 to 600 ms of ballistic MVC activity, and this was interpreted as global recruitment/rate coding of masseteric motor units. PMID- 1517875 TI - Use of shell crowns in Hong Kong dental hospital attenders. AB - In 1984 an oral health survey of Hong Kong adults aged 35-44 years revealed that 15% of subjects presented with metal shell crown restorations, often as components of fixed-bridge reconstructions. The aim of this study was to describe the patterns and means of use of shell crowns, and to describe the patterns of tooth loss in patients who presented with such restorations, attending for treatment at the dental teaching hospital in Hong Kong over a 2-year period. A total of 1563 such patients attended. The records, which included radiographs, of 165 of these patients aged 35 years and above, obtained by means of a systematic sampling frame, were studied by one trained examiner. On initial presentation each patient was found to have a mean of 4.0 shell crowns, 77% of these being components of bridge restorations. The bridges involved a mean of only 3.9 units (retainers and pontics). The tooth type most commonly replaced by a bridge of this type was the first molar. It was concluded that most shell crowns used in this patient group are abutment retainers for predominantly short-span bridge restorations. PMID- 1517876 TI - Number and intensity of occlusal contacts following surgical correction of mandibular prognathism. AB - The aim of the present investigation was to study the changes in the number and intensity of occlusal tooth contacts in the intercuspal position following surgical correction of mandibular prognathism. The study sample consisted of 33 adults with mandibular prognathism whose management included bilateral vertical ramus set-back osteotomy and combined orthodontic treatment. Measurement of the number and intensity of occlusal tooth contacts was performed by means of the photocclusion technique. Recordings of the number and intensity of occlusal contacts were made 1 day before operation and 6 months post-surgery. Testing of the differences of the means for both the number of occlusal contacts and their intensity between the two phases was achieved by means of a paired t-test. The results of the study showed that the combined orthodontic and surgical treatment produced a significant increase (P less than 0.001) in the number and intensity of occlusal contacts (4.54 and 160 kg mm-2 respectively). However, whether this increase in occlusal contacts resulted in an overall improvement in craniomandibular functional status cannot be answered by the present study. PMID- 1517877 TI - Bond strength and rupture properties of some soft denture liners. AB - The bond strength and rupture properties of three soft acrylic liners (Coe-Soft, Coe Super-Soft and Vertex Soft) and two silicone liners (Molloplast-B and Flexibase) were tested immediately after processing and following immersion in water at 37 degrees C for 7 and 90 days. The bond test gave variable results, as some materials partly peeled and then stretched until rupture occurred. After saturation the acrylic liners exhibited an increase in tear resistance, whilst silicone materials deteriorated, in the case of Flexibase to approximately 25% of its original value. Vertex Soft was the exception, as tear resistance decreased as water sorption increased. Scanning electron microscopy revealed indefinite demarcation between soft acrylic resins and hard denture base, which was not altered after saturation in water. On the other hand, the interface between denture base and silicone liners was clearly visible before and after saturation. The results indicated that denture soft liners had variable water sorption values depending on their basic structure, and some properties changed after immersion in water, a finding that is of relevance to prosthodontic practice. PMID- 1517878 TI - Muscles, mitochondria and myalgia. PMID- 1517879 TI - Interphase cytogenetics of tumours. PMID- 1517880 TI - A novel lamina lucida component of epithelial and endothelial basement membranes detected by LH39 monoclonal antibody. AB - The murine monoclonal antibody, LH39 was characterized in this study and appeared to bind to a novel basement membrane epitope. This antigen was expressed in the epithelial basement membrane of human tissue derived from all three germ cell layers and in basement membranes surrounding small blood vessels within the stroma of all organs examined. LH39 antigen could be first detected in fetal skin at the dermo-epidermal junction at 7 weeks estimated gestational age but was not present in the dermal vasculature until 16 weeks. When tested against tissue from a range of lower mammalian species, LH39 antigen appeared to be primate-specific. The epithelial basement membrane zone in organotypical cultures, where there is de novo synthesis of basement membrane components, contained abundant LH39 antigen in contrast to other basement membrane components, type IV collagen, laminin, and type VII collagen. Ultrastructural localization of LH39 epitope, using immunogold electron microscopy on unfixed freshly frozen tissue, was to the lamina lucida. No cross-reactivity could be detected between LH39 and laminin, fibronectin, and collagens I, III, IV, and V using the ELISA assay. In vitro studies with a range of proteolytic enzymes suggested that the antigen was non collagenous in nature. LH39 precipitated a polypeptide with a molecular weight of 185 kD from extracts of metabolically labelled cultured keratinocytes, and polypeptides of 185 and 200 kD from the culture medium. The tissue distribution of LH39 antigen suggested that it may be an epitope within anchoring filaments. Potential applications of this antibody include the study of benign and malignant human vascular disorders, diseases and tumours associated with angiogenesis, epithelial neoplasms, and conditions of tissue regeneration and repair, such as wound healing. PMID- 1517881 TI - Sequential dermal microvascular and perivascular changes in the development of scleroderma. AB - It has been previously proposed that there is a primary microvascular abnormality in patients with systemic sclerosis. In this study using conventional light and electron microscopy, immunohistochemistry, and labelled adenosine uptake techniques, changes in the dermal microvasculature have been related to the various clinical stages of skin disease in systemic sclerosis. The earliest pathological changes are seen in clinically normal skin. They constitute changes in endothelial cell function and their consequences. Perivascular oedema is an early feature. With progression in the clinical disease, there is, at first, an inflammatory cell infiltrate into the dermis, particularly the papillary and mid dermis, and platelet aggregation within vessels. Further clinical progression is associated with increasing dermal fibrosis, loss of adnexae, and vascular effacement. It is postulated that the recruitment of different types of mononuclear cells into the dermis is causally linked with the preceding endothelial cell dysfunction and the subsequent induction of fibroblast proliferation and collagen synthesis. PMID- 1517882 TI - Human coronary microvessels in diabetes and ischaemia. Morphometric study of autopsy material. AB - The objective of this study was to test the hypothesis that excessive severity of ischaemic heart disease in diabetics is due, in part, to capillary inadequacy. Sections from autopsied hearts of diabetic patients with and without myocardial infarction as well as from those of patients with infarcts and no diabetes were used for morphometric studies of intramural microvessels in areas without infarction. Normoglycaemic patients with normal hearts were also examined. Two to five transverse sections from each of 44 hearts (stained with methenamine silver) were examined for capillary numerical density, capillary to myofibre ratios, and myofibre diameters. Averages for each case and totals for each group were calculated and compared. Normoglycaemic patients with infarcts had increased morphometric values. Diabetics with infarcts had significantly lower capillary densities than the other groups. In conclusion, it is suggested that in diabetes there is an inadequate ischaemia-induced, reactive angiogenesis. This may contribute towards increased myocardial vulnerability in further ischaemic injury and perhaps to diabetic cardiomyopathy. PMID- 1517883 TI - A tumour promoter induces alterations in vinculin and actin distribution in human renal epithelium. AB - Loss of cell-substratum adhesion is an important factor during tumour progression. We have previously described reduced focal contact components and poorly organized cytoskeletal actin in renal cell carcinomas. In this study, we have used the potent tumour promoter TPA on cultured human renal epithelium to mimic neoplastic transformation. The morphological changes induced by TPA were examined by phase contrast and fluorescence microscopy. TPA treatment caused rounding up of cells and loss of adhesion to either fibronectin or laminin substrata. Cytoskeletal actin was redistributed from orientated stress fibre bundles to a perinuclear circumferential arrangement. This was accompanied by a progressive reduction in the number of vinculin-containing contacts with accumulation of vinculin in punctate spots in the perinuclear region. These altered membrane-cytoskeletal interactions induced by TPA are entirely reversible and mimic epigenetic changes which occur during tumour progression. PMID- 1517884 TI - Cyclosporin reduces proteinuria in rats with aminonucleoside nephrosis. AB - The effect of cyclosporin (CS) was assessed in Sprague-Dawley rats with puromycin aminonucleoside (PA) nephrosis induced by a single intraperitoneal injection of PA. Three groups of rats were injected intraperitoneally with CS (10 mg/kg body weight) daily, beginning 1 day before PA administration, or 5 or 10 days after PA administration, for 10 days. CS significantly reduced proteinuria in rats with PA nephrosis in comparison with untreated nephrotic controls. After discontinuation of the CS treatment, proteinuria gradually increased, reaching values similar to those in control nephrotic rats. CS pretreatment did not prevent the induction of PA-induced nephrotic syndrome. Light microscopy and assessment of anionic sites in the glomerular basement membrane revealed no differences between normal rats, nephrotic controls, and CS-treated rats. These results show that CS can reduce proteinuria in PA nephrosis, but cannot ameliorate the glomerular changes. PMID- 1517885 TI - Apposition of fibroblasts to mast cells and lymphocytes in normal human lung and in cryptogenic fibrosing alveolitis. Ultrastructure and cell perimeter measurements. AB - The perimeters of mast cells and lymphocytes in human lungs were measured in electron micrographs by digitizer to determine the percentage of perimeter apposed to fibroblast (PPAF). Fibroblasts were apposed to the majority of mast cells. The median PPAF for mast cells in normal lung was 50.3 per cent, and in cryptogenic fibrosing alveolitis (CFA), 35.7 per cent. Although the value in CFA was lower, the difference was not statistically significant (median difference 11.8; 95 per cent confidence interval (-19.6, 25.1); P = 0.65). The PPAF range overall was 3.8-94.1 per cent. There was similar apposition of fibroblasts to lymphocytes, and no statistical differences were found when median PPAF results for mast cells and lymphocytes were compared for normal and CFA lung. The high degree of percentage apposition, accurately quantified in this study, shows that fibroblasts, mast cells, and lymphocytes are ideally arranged structurally in normal alveolar walls, to facilitate the many physiological interactions which are currently being uncovered. The present study also shows that apposition persists in pathological states, e.g., CFA lung, but because all these cells are increased in number in CFA lung, apposition is easier to identify here than in normal lung. PMID- 1517886 TI - Myoendothelial contacts in the thoracic aorta of rat fetuses. AB - There is increasing documentation of the presence of endothelial-smooth muscle communication in both small and large arteries. We have found that morphological evidence of these contacts appears early in development. Intimate contacts between endothelial and muscle cells in the thoracic aorta of normal rat fetuses have been studied with transmission electron microscopy. These myoendothelial contacts were seen in the form of cytoplasmic projections passing through fenestrae in the elastic lamellae. Most of these cell processes seem to arise from the muscle cells and they usually have a club-shaped configuration. The specific nature of the cell-cell contact was predominantly via simple appositions with an intercellular space of 6-15 nm. Myoendothelial contacts are potential sites for electrical and metabolic communication between elements of the intima and media, ensuring that the vessel wall works as a unit. The demonstrated necessity of intact endothelium for smooth muscle cell response to load may depend on this type of contact. PMID- 1517887 TI - X-ray microanalysis of bulk hydrated specimens of neoplastic and non-neoplastic human urothelium. AB - Specimens of neoplastic and non-neoplastic human urothelium were rapidly frozen against a copper block immersed in liquid nitrogen, planed in a cryoultramicrotome and then examined by low-temperature scanning electron microscopy (LTSEM) following coating by aluminium. Energy dispersive X-ray microanalysis (XRMA) was performed on the superficial urothelial cells and on gelatin blocks mounted in parallel which had known concentrations of sodium, potassium, chloride, and phosphorus. The neoplastic urothelial cells had significantly less phosphorus (P less than 0.05) than non-neoplastic cells and the ratios K+/P,K+/Na+, and K+/Cl- were significantly higher in neoplastic cells than in non-neoplastic cells (P less than 0.00001). These results are consistent with those expected in cells with a sustained increase in intracellular pH caused by stimulation of Na+/H+ ion membrane exchange. PMID- 1517888 TI - Flow cytometry. PMID- 1517889 TI - P53 in tumour pathology: can we trust immunocytochemistry? PMID- 1517890 TI - Macrophage and perisinusoidal cell kinetics in acute liver injury. AB - Perisinusoidal cells (PSCs) are currently regarded as the major source of extracellular matrix proteins during hepatic fibrogenesis in response to liver injury. However, the cellular mechanisms underlying their response to injury are not fully understood. One hypothesis is that the PSCs are stimulated by peptide growth factors produced by hepatic macrophages (Kupffer cells) in response to parenchymal cell damage. In this study we have investigated the kinetics of the PSC and macrophage populations in acute carbon tetrachloride-induced hepatic injury in rats. PSCs were identified immunohistochemically by detection of cytoplasmic desmin; monocytes and macrophages were detected using the monoclonal antibodies ED1 and ED2; cells in S phase were identified by immunohistochemical detection of nuclear-incorporated bromodeoxyuridine. The results showed an expansion of the desmin-positive PSC population, predominantly within the damaged perivenular zones, which reached a peak on days 3 and 4 following administration of carbon tetrachloride; this was contributed to by local PSC proliferation. The PSC response was preceded by an expansion of the macrophage population resulting from both local macrophage proliferation and influx of blood monocytes. These results are in keeping with the hypothesis that the PSC response to acute liver injury is mediated, at least in part, by hepatic macrophages. PMID- 1517891 TI - Malignancy grading of the deep invasive margins of oral squamous cell carcinomas has high prognostic value. AB - Several recent studies have indicated that cells at the invasive tumour margins often are different from cells within other parts of various human cancers. In this work, we have studied all squamous cell carcinomas of the floor of the mouth registered in Norway during the years 1963-1972 (N = 96). Borderline cases and cases given no treatment were excluded. Of the remaining 79 cases, biopsy specimens acceptable for histological grading were obtained from 61 patients. Only the most invasive margins of the tumours were histologically graded independently by two pathologists according to a multifactorial grading system. The results confirmed our previous findings that grading of invasive tumour margins is an independent prognostic factor in Cox's multivariate survival analysis (P less than 0.01). Inter-observer agreement was calculated by kappa statistics, and good agreement was obtained (kappa = 0.63). Neither agreement nor prognostic value was improved after calibration of the pathologists. Conventional Borders' grading of the whole biopsy had no prognostic value (P less than 0.38). We conclude that invasive cell grading may be of value for treatment planning of oral cancers, and that further studies of the deep, invasive parts of oral and other cancers are needed in order to obtain a better understanding of tumour cell invasion and metastasis. PMID- 1517892 TI - Image analysis in the discrimination of verrucous carcinoma and squamous papilloma. AB - Verrucous carcinoma is a differentiated variant of squamous cell carcinoma and may present diagnostic difficulties as it may be erroneously diagnosed as squamous papilloma. In this study, the sizes of the intermediate cells in these two conditions were measured by means of morphometric analysis. Biopsies from 28 patients with verrucous carcinoma, 25 patients with squamous papilloma, and ten squamous cell carcinomas were analysed. A significant difference was shown (P less than 0.001) by an uncorrelated t-test between verrucous carcinoma and squamous papilloma. The former had a mean cell area of 373 microns 2 and the latter 184 microns 2. Squamous cell carcinomas differed from the other two neoplasms by their large range of cell areas both within and between cases. Thus, image analysis can be of diagnostic help in cases where no firm initial histopathological diagnosis can be obtained. The diagnosis should be made on morphological grounds, but a mean cell area greater than 300 microns 2 supports a diagnosis of verrucous carcinoma whereas an area less than 250 microns 2 supports a diagnosis of squamous papilloma. PMID- 1517893 TI - Degranulation of cystic fibrosis nasal polyp mast cells. AB - The ultrastructure of nasal polyps from cystic fibrosis (CF) patients was compared with non-CF nasal polyps in this study. Morphometric analysis showed that CF nasal polyps contained greater numbers of mast cells, endothelial cells, lymphocytes, and plasma cells compared with the non-CF specimens. Morphologic evidence of degranulation was seen in approximately 30 per cent of the CF mast cells but was not observed in the non-CF mast cells. Increased numbers of small granules, vacuolated granules, and lipid bodies were noted in the CF compared with the non-CF nasal polyp mast cells. Also observed was a decrease in collagen in the extracellular space of the CF nasal polyps compared with the non-CF specimens. Although eosinophils were observed in the non-CF nasal polyp tissue, these leukocytes were absent in the CF nasal polyps. These data indicate that striking morphologic differences exist between CF and non-CF nasal polyps with mast cell degranulation, a salient feature of CF specimens. PMID- 1517894 TI - Improve your hospital autopsy rate to 40-50 per cent, a tale of two towns. AB - In the light of medical audit, all pathology departments are scrutinizing their hospital autopsy rate. In most countries, the rate has fallen over the last few decades to between 10 and 20 per cent. However, it is still possible to achieve a much higher rate. We compare two neighbouring District General Hospitals (DGHs): Northampton, with the more usual autopsy rate of 11 per cent, and Kettering, with a higher rate of 40-50 per cent. These hospitals are comparable in almost every way except for the system used to request permission for an autopsy. These differences were evaluated and the following factors were found to be of importance in achieving a high rate: (1) centralization of death certificates within the mortuary and personal contact between the certifying doctor and the relatives within the bereavement room; (2) mortuary pathology technicians are designated as bereavement officers and act as coordinators between relatives, clinicians, and pathologists; and (3) regular clinico-pathological meetings and a positive attitude to autopsies by clinicians. PMID- 1517895 TI - The fractal dimension may be a useful morphometric discriminant in histopathology. AB - The hypothesis is presented that fractal geometry, and the fractal dimension in particular, is likely to be a more useful method of image analysis in histopathology than the use of regular Euclidean geometry. The concept of the fractal dimension is described and it is suggested that many human tumours have a fractal structure over a wide range of scales. It is postulated that the fractal dimension will be useful in discriminating between different diagnostic categories and may also allow more precise prognostic stratification within single diagnostic groups. PMID- 1517896 TI - The attitudes of junior pathologists towards the autopsy. PMID- 1517897 TI - Carcinoid vs. paraganglioma and adenoma vs. carcinoid. PMID- 1517898 TI - Measurement of Breslow depth. PMID- 1517899 TI - A two-colour technique for chromosome in situ hybridization in tissue sections. AB - By extending non-isotopic in situ hybridization of DNA probes (targeted to metaphase chromosomes or interphase nuclei) to hybridization using tissue sections, additional topological information on the DNA structure and specific alterations can be obtained. We have established a method for the application of two different, chromosome-specific probes labelled with two colour dyes allowing simultaneous detection of two-colour signals. This method was tested in and is applicable to tissue sections of various origins. To demonstrate its sensitivity, prostate carcinomas (either as cryosections or as sections from paraffin blocks) were investigated for the presence or absence of chromosomes 1 and Y. The technique presented here, comparable to immunohistochemical staining, is particularly useful for routine application in diagnostic laboratories and testing of fresh or archival material. PMID- 1517900 TI - Parathyroid hormone-related peptide: expression in fetal and neonatal development. AB - Hypercalcaemia frequently complicates the clinical management of cancer. Many factors have been implicated in the pathogenesis of this humoral hypercalcaemia of malignancy, the most recent candidate being parathyroid hormone-related peptide (PTHrP). Until now, this peptide has been detected only in some normal and transformed adult tissues. In recent years, it has become apparent that tumours are capable of expressing and secreting factors previously elaborated only during fetal life. Many of these factors act to stimulate the growth of both tumour and fetal cells in an autocrine manner. The data presented here demonstrate that PTHrP is expressed in the human and rat fetus throughout gestation. Immunocytochemistry reveals a gestationally related, changing pattern of expression which is paralleled by changes in mRNA transcription. These data support the hypothesis that PTHrP may function as a fetal growth factor. PMID- 1517901 TI - Seminal vesicle amyloid: the first example of exocrine cell origin of an amyloid fibril precursor. AB - Amyloid fibrils have been extracted from seminal vesicles, and a dominant 14 kD amyloid fibril protein has been identified. An antiserum to this protein reacted both with amyloid and with epithelial cells in some normal seminal vesicles. These reactions were blocked with seminal vesicle secretion and seminal vesicle amyloid fibril protein, but not by degraded amyloid fibrils or fibril protein from other types of amyloid. It is concluded that seminal vesicle amyloid is derived from secretory proteins of the seminal vesicles. As such, it is the first amyloid described which appears to be the product of an exocrine secretory cell. PMID- 1517902 TI - 'Pleural' and pulmonary carcinosarcomas. AB - The histological distinction between carcinosarcoma and mesothelioma has received little attention. The object of this study was to describe the histology and immunohistochemistry of two carcinosarcomas presenting as pleural tumours. These were compared with 12 carcinosarcomas from sites within the lung, and with the established features of mesothelioma. Histologically and immunohistochemically, these 'pleural' carcinosarcomas are similar to conventional pulmonary carcinosarcomas but accurate recognition is hindered by their gross appearance and biphasic histology which closely mimic mesothelioma. They may exhibit features such as neutral mucin, expression of carcinoembryonic antigen, squamous differentiation, and neuroendocrine differentiation which, when present, are evidence against mesothelioma. These tumours are rare and have passed unnoticed until now. PMID- 1517903 TI - Immunopathological changes in the skin following recombinant interleukin-2 treatment. AB - The systemic administration of the cytokine recombinant interleukin-2 (rIL-2) is associated with a number of toxic effects, including dermatological complications. The clinical, histological, and immunopathological changes occurring in the skin of six patients receiving rIL-2 for metastatic colorectal carcinoma have been studied. All of the patients developed a diffuse erythema shortly after initiation of the treatment. In one patient, generalized erythroderma and photosensitivity developed. The initial biopsy revealed patchy spongiosis, focal exocytosis, and focal basal layer damage with a perivascular chronic inflammatory cell infiltrate. With further treatment there was progressive thickening of the epidermis. Immunohistochemistry revealed changes in the expression of CD1, CD3, CD4, and CD25, particularly on perivascular cells. Additionally, there was an increase in the expression of intercellular adhesion molecule-1 (ICAM-1) on keratinocytes in the basal and mid-layers of the epidermis, endothelial cells, and perivascular cells. It is hypothesized that the expression of ICAM-1 by the epidermal keratinocytes may be the important event in initiating the cutaneous manifestations associated with rIL-2 administration. PMID- 1517904 TI - Induction of emphysema and bronchial mucus cell hyperplasia by intratracheal instillation of lipopolysaccharide in the hamster. AB - The aim of this study was to determine whether lipopolysaccharide-induced elastase release from recruited neutrophils in the hamster lung would induce emphysema, measured by mean linear intercept (Lm) and bronchial mucus cell hyperplasia (BMCH), scored in tissue sections stained with periodic acid-Schiff. Lipopolysaccharide (LPS) was instilled transorally twice a week for up to 5 weeks in hamsters. At 4 weeks after seven LPS instillations, Lm amounted to 87.6 +/- 1.2 microns, while it was 68.3 +/- 1.5 microns after seven saline instillations (P less than 0.01). At 6 months after the sixth LPS instillation, the Lm of these lungs was 83.3 +/- 1.6 microns, indicating irreversible tissue destruction. LPS treated hamsters showed marked to severe BMCH, which was most evident in large intrapulmonary airways. Instillations of highly selective inhibitor of hamster PMN elastase resulted in 50 per cent inhibition of LPS-induced emphysema. The development of BMCH was inhibited by approximately 35 per cent by this agent. To study the response in time of cellular infiltration after a single LPS instillation, the lungs of groups of four hamsters were lavaged at different time points. PMN recruitment showed peak values at 4 and 48 h after LPS instillation and returned to baseline values at 96 h. Simultaneous intratracheal instillation of LPS and anti-TNF alpha antiserum resulted in a considerable reduction of neutrophil influx into bronchoalveolar spaces in the first 6 h after instillation. PMID- 1517905 TI - Diagnosis and treatment of fetal urinary tract abnormalities. PMID- 1517906 TI - Impact of within-person variability on identifying children with hypercholesterolemia: Framingham Children's Study. AB - BACKGROUND AND OBJECTIVE: The National Cholesterol Education Program guidelines recommending that children be screened to detect abnormal levels of blood lipids depend on accurate assignment to risk categories. Our objective was to assess the impact of within-person variability of blood lipids on such risk classification. DESIGN AND SUBJECTS: We measured total cholesterol (TC) and high-density lipoprotein-cholesterol (HDL-C) at three successive weekly visits in 24 children aged 6 to 9 years. MAIN OUTCOME MEASURES: Using within-person variance estimates, we constructed 95% confidence intervals to evaluate how well one, two, and three lipid measurements per child allowed assignment of risk as recommended by the National Cholesterol Education Program. RESULTS: The mean, overall, and within person standard deviations were 145.7, 24.5, and 9.2 mg/dl, respectively, for TC, and 42.8, 10.1, and 4.6 mg/dl, respectively, for HDL-C. One TC measurement allowed confident assignment to the "acceptable" (less than 170 mg/dl) category only if less than 154.9 mg/dl, and to the "high" (greater than or equal to 200 mg/dl) category only if greater than 215.1 mg/dl. The average of two TC values allowed assignment to these categories if less than 159.3 or greater than 210.7 mg/dl, respectively. For the average of three TC values, these ranges were less than 161.3 and greater than 208.7 mg/dl, respectively. With one TC measurement, no value allowed assignment to the "borderline" (170 to 199 mg/dl) category. The average of two TC values allowed assignment to the "borderline" category if between 180.7 and 189.3 mg/dl. Using the average of three values enlarged this range by 4 mg/dl. For HDL-C, multiple measurements improved risk assignment in a similar fashion. CONCLUSION: The magnitude of within-person variability of TC and HDL-C limits the ability to classify children into risk categories recommended by the National Cholesterol Education Program. PMID- 1517907 TI - Improved outcome of respiratory syncytial virus infection in a high-risk hospitalized population of Canadian children. Pediatric Investigators Collaborative Network on Infections in Canada. AB - PURPOSE: To determine the outcomes in children at high risk for death or complications from respiratory disease who are hospitalized with respiratory syncytial virus (RSV) infection. DESIGN: Retrospective chart review. SETTING: Twelve pediatric tertiary care centers. PATIENTS: All hospitalized children with an RSV infection diagnosed by a positive antigen detection test result or viral isolation during the study period from 1988 to 1991, encompassing three winter seasons. Charts from patients in the following high-risk groups were reviewed in detail: (1) congenital heart disease, (2) chronic lung disease, (3) immunodeficiency, (4) age less than 6 weeks, (5) gestational age less than 36 weeks, and (6) hypoxia (defined as oxygen saturation less than 90% or arterial oxygen pressure less than 60 mm Hg). MEASUREMENTS: The age of all children, the date of RSV identification, and the use of oxygen supplementation, intensive care, and ventilatory support. In addition, the duration of these treatments and the duration of hospitalization were noted. Left-to-right shunting and pulmonary hypertension before RSV infection were determined in those children with congenital heart disease. The nature of the chronic lung disease was noted. Death within 2 weeks of RSV identification was recorded, and the use of ribavirin, bronchodilators, and corticosteroids was determined. RESULTS: Significant year-to year variation in the frequency of RSV infection was confirmed, with a peak during the 1989-1990 winter noted by the majority of centers (p = 0.0001). Of the 1584 patients in the study, 260 had underlying cardiac disease, 200 had chronic lung disease, 35 had compromised immune function, 378 had been premature, 373 were less than 6 weeks of age, and 338 had hypoxia. Seventeen patients died within 2 weeks (mortality rate 1%); significantly more patients with underlying cardiac disease (3.4%) or lung disease (3.5%) died. Immunocompromised patients had the longest hospital stay (median 39 days), followed by those patients with underlying cardiac or pulmonary disease (11 days); patients less than 6 weeks of age (5 days) and those with hypoxia (6 days) had the shortest hospital stays. Patients with underlying cardiac and pulmonary disease also required oxygen supplementation for a significantly longer period. CONCLUSION: The year-to-year variation in frequency of RSV infection was confirmed in this study. Morbidity and mortality rates associated with RSV infection in a high-risk population in Canada were significantly lower than previously reported. PMID- 1517908 TI - Efficacy and safety of a Haemophilus influenzae type b capsular polysaccharide tetanus protein conjugate vaccine. AB - A polyribosylribitol phosphate (polysaccharide)-tetanus protein conjugate vaccine (PRP-T) against Haemophilus influenzae type b (Hib) was evaluated for safety and efficacy after vaccination of more than 100,000 infants. No major side effects were attributed to the vaccine. Immunogenicity studies showed an antibody response in 70% to 100% of infants after two doses, and in 98% to 100% of infants after three doses, within the first 6 months of life. Antibodies persisted in 90% of recipients, in whom significant anamnestic responses developed after a booster dose at 18 months of age. In comparison with other available Hib vaccines, PRP-T induces equal or higher mean titers after three doses. Although licensure of other vaccines interrupted controlled efficacy trials, up to that point five cases of Hib disease in those trials had occurred in placebo recipients, and no Hib disease has been reported in the more than 100,000 vaccinated infants who have received more than one dose of PRP-T. Thus PRP-T combined immunogenicity early in life with induction of immunologic memory. PMID- 1517909 TI - Protection against infection with Giardia lamblia by breast-feeding in a cohort of Mexican infants. AB - To determine whether breast-feeding protects infants against symptomatic and asymptomatic infection by Giardia lamblia, we followed 197 infants in a poor area of Mexico City from birth to 18 months of age; symptoms and feeding status were recorded weekly. Stool specimens were collected every 1 to 2 weeks and tested for Giardia by enzyme-linked immunosorbent assay. A mean of 1.0 Giardia infection per child-year was detected; 94 infants had a total of 139 infections; 17% of infections were symptomatic. Ninety-one percent of infants were breast fed from birth and 38% were breast fed at 1 year of age. Lack of breast-feeding was a significant risk factor for first Giardia infection at all ages. The adjusted incidence rate ratio for first Giardia infection for none versus complete breast feeding was 5.0 (confidence interval (CI) 1.5 to 16.9; p = 0.009), and for none versus any breast-feeding, 1.8 (CI 1.1 to 2.8; p = 0.013). Symptomatic Giardia infection was also associated with lack of breast-feeding (none vs any: incidence rate ratio = 2.5; CI 0.9 to 6.8; p = 0.077), but breast-feeding did not protect against chronic carriage of Giardia. Other significant risk factors for Giardia infection were presence of animals in the household (p = 0.005) and the use of water or nonmilk liquid for infant feedings (p = 0.035). We conclude that breast feeding protects infants against Giardia by mechanisms that include preventing the establishment of infection. PMID- 1517910 TI - Immunologic changes associated with the development of tolerance in children with cow milk allergy. AB - The purpose of this study was to determine whether cow milk-specific antibody responses correlated with the development of clinical tolerance in cow milk allergic children. Double-blind, placebo-controlled food challenges were performed annually in 29 patients with cow milk allergy. Clinical reactivity was lost in 11 (38%) of 29 patients. The median age for all patients at the time of diagnosis by these food challenges was 3 years; more than 80% of patients in each group had atopic dermatitis as part of their presenting symptoms. Casein-specific and beta-lactoglobulin-specific IgE, IgG, IgG1, and IgG4 antibody concentrations were analyzed in all patients at regular intervals. In the patients becoming clinically tolerant to cow milk, the IgE-specific antibody concentrations and IgE/IgG-specific ratios for both milk proteins were lower initially and decreased significantly with time, in comparison with those in the group who retained clinical sensitivity. The concentrations of IgG1- and IgG4-specific antibody to casein and the IgE/IgG1 and IgE/IgG4 ratios for both casein and beta lactoglobulin were significantly less in the patients losing clinical reactivity. No differences in the IgG-specific concentrations were observed in either group at any of the evaluation times noted above. Monitoring similar casein-specific and beta-lactoglobulin-specific IgE concentrations and IgE/IgG ratios may help predict which patients will ultimately lose their clinical reactivity to cow milk. PMID- 1517911 TI - Renovascular disease in childhood. AB - Fifty-four children referred for investigation of hypertension had renovascular disease. In eight patients it was associated with neurofibromatosis, in three with idiopathic hypercalcemia of infancy, and in five cases it followed an arteritic illness. Fibromuscular dysplasia was the underlying abnormality in the majority of cases (46%). Twenty-six patients (48%) were first seen with accelerated hypertension; 38 children (70%) had bilateral renal arterial disease, and in 41 (76%), disease of the small intrarenal vessels was found. Renal vein renin ratios indicated unilateral disease in 31 cases; the results correlated with arteriography findings in 32 (62%) of 51 patients. Eleven children also had the middle aortic syndrome, and 9 of 16 patients, investigated by cerebral arteriography because of cranial bruits or focal neurologic signs, had cerebral vascular abnormalities. Twenty patients were treated surgically--10 by reconstructive procedures, 11 by nephrectomy or heminephrectomy, and 6 by transluminal angioplasty. Of these, 9 (45%) are normotensive with no treatment, 10 have a decreased requirement for antihypertensive drugs, and 1 had no improvement. Thirty-four patients were treated medically because of the extent of their disease; two patients have died of hypertensive complications. We conclude that renal vascular disease in children is often widespread, may be associated with intracerebral vascular disease, frequently affects both kidneys, including both intrarenal and extrarenal vessels, and is therefore not always amenable to surgical intervention and cure. PMID- 1517912 TI - Use of a molecular genetic approach to diagnosing the fragile X genotype. AB - We report the direct molecular detection of the fragile X genotype in 111 individuals from 17 families with a total of 31 cases of fragile X syndrome. Comparison of our molecular data with our previous cytogenetic and linkage data from these same families indicates the effectiveness of the direct molecular analysis. We have been able to assign a genotype unambiguously in 100% of the persons tested, and in all cases the molecular data correlated with the cytogenetic or linkage findings or both. Two of the three families presented in this study represent inheritance of this gene through normal transmitting males, and the third is strongly suggestive of this mode of inheritance. Our data show that the direct molecular approach will be of great utility for confirmation of the diagnosis and for the detection of female carriers and normal transmitting males who are at high risk for having affected children or grandchildren. PMID- 1517913 TI - Hypercapnic and hypoxic ventilatory and cardiac responses in school-aged siblings of sudden infant death syndrome victims. AB - Siblings of sudden infant death syndrome (SIDS) victims have been shown to have abnormal ventilatory patterns and altered responses to respiratory stimuli during infancy. To evaluate whether these abnormalities persist, we studied ventilatory responses in 20 older SIDS siblings (9.8 +/- 0.9 (mean +/- SEM) years of age) and 20 control subjects (10.2 +/- 0.9 years of age). To evaluate hypercapnic ventilatory responses, we had subjects rebreathe 5% carbon dioxide and 95% oxygen until end-tidal carbon dioxide tension reached 65 mm Hg. Instantaneous minute ventilation, mean inspiratory flow, and respiratory rate were calculated breath by breath. Hypercapnic responses did not differ between SIDS siblings (2.08 +/- 0.14 L/min per mm Hg) and control subjects (1.90 +/- 0.10 L/min per mm Hg; not significant). To assess hypoxic ventilatory responses, we asked subjects to rebreathe 13% oxygen and 7% carbon dioxide, with the balance nitrogen, at mixed venous end-tidal carbon dioxide tension, until arterial oxygen saturation by pulse oximetry fell to 75%. No differences in hypoxic ventilatory responses were found between the SIDS siblings (-1.39 +/- 0.15 L/min/% saturation) and the control subjects (-1.22 +/- 0.17 L/min/% saturation; not significant). The mean inspiratory flow, tidal volume, respiratory rate, and heart rate responses to hypercapnia and hypoxia were also similar in the two groups. We conclude that there is no difference in hypercapnic and hypoxic ventilatory and cardiac responses, as assessed by rebreathing techniques, between school-aged SIDS siblings and control subjects. We speculate that in SIDS siblings the control of breathing is immature during infancy and that they achieve maturity of control and resolution of breathing abnormalities with time. PMID- 1517914 TI - Vitamin A supplementation and bronchopulmonary dysplasia--revisited. PMID- 1517915 TI - Intravenous immune globulin therapy for sepsis in premature neonates. PMID- 1517916 TI - Ataxia-telangiectasia in a child with vaccine-associated paralytic poliomyelitis. AB - Vaccine-acquired poliomyelitis developed in a nonimmunized 10-month-old boy. At age 4 years, ataxia-telangiectasia was recognized. We conclude that the occurrence of vaccine-related poliomyelitis warrants a detailed assessment of immunity, and that, in patients with ataxia-telangiectasia, the use of live vaccines may be hazardous, even in those with apparently normal immunity. PMID- 1517917 TI - Familial hypotonia of childhood caused by isolated 3-methylcrotonyl-coenzyme A carboxylase deficiency. AB - Hypotonia was the initial symptom in four siblings from a nonconsanguineous Tunisian-Jewish family. Plasma carnitine was severely deficient, and urinary organic acid analysis revealed increased excretion of 3-hydroxyisovaleric acid and 3-methylcrotonylglycine. 3-Methylcrotonyl-coenzyme A carboxylase activity was reduced in skin fibroblasts; pyruvate carboxylase and serum biotinidase activities were normal. We conclude that 3-methylcrotonyl-coenzyme A carboxylase deficiency should be added to the list of metabolic causes of familial hypotonia of childhood. PMID- 1517918 TI - Variability of breath hydrogen excretion in breast-fed infants during the first three months of life. AB - Breath hydrogen excretion was measured serially in breast-fed infants. There was marked variability in H2 excretion, both within and between infants. The findings indicate that unabsorbed food is not the only substrate, and that breath H2 may not be an effective method to assess carbohydrate absorption in young infants. PMID- 1517919 TI - Bentiromide test using liquid-chromatographic measurement of p-aminobenzoic acid and its metabolites for diagnosing pancreatic insufficiency in childhood. AB - We assessed the diagnostic capability of the bentiromide test using a high pressure liquid-chromatography method to analyze p-aminobenzoic acid and its metabolites in plasma as an indirect measure of exocrine pancreatic function. Mean total amine concentration in pancreatic-insufficient subjects was significantly lower than in control subjects. There were 3 of 15 false-negative results and no false-positive results. We conclude that this chromatographic method is an effective means of analyzing p-aminobenzoic acid and its metabolites after ingestion of bentiromide. PMID- 1517920 TI - High synovial immunoglobulin E levels in eosinophilic synovitis. AB - Eosinophilic synovitis occurred in a 7-year-old boy. Synovial fluid leukocytes were mostly eosinophils; the peripheral blood showed only mild eosinophilia. The level of eosinophil-derived neurotoxin in the synovial fluid was higher than that in the serum, suggesting intraarticular eosinophil degranulation. The IgE level was also elevated in the synovial fluid (3854 ng/ml) but normal in the serum (408 ng/ml), suggesting a localized immediate hypersensitivity immune response. PMID- 1517921 TI - Trial of vitamin A supplementation in very low birth weight infants at risk for bronchopulmonary dysplasia. AB - We performed a randomized, double-blind, controlled trial to determine whether vitamin A supplementation in a group of very low birth weight infants would reduce the incidence of bronchopulmonary dysplasia. Forty-nine infants (birth weight 700 to 1100 gm) requiring mechanical ventilation and supplemental oxygen at 96 hours age were randomly assigned to receive either 2000 IU retinyl palmitate (n = 27) or saline placebo (n = 22) intramuscularly every other day for up to 14 doses. There were no differences between treatment groups in the incidences of bronchopulmonary dysplasia at 31 days of postnatal age (vitamin A group 48%, placebo group 55%; p = 0.776), supplemental oxygen requirement at 34 weeks of postconceptional age, or other complications of prematurity. The vitamin A group had higher mean plasma vitamin A concentrations than the placebo group, but mean plasma vitamin A concentrations were greater than 20 micrograms/dl (suggesting sufficiency) in both groups after the first study week. By study day 28, only one fourth of the infants in either group had plasma vitamin A concentrations less than 20 micrograms/dl. In contrast to an earlier report, we found no change in the incidence of BPD with vitamin A supplementation. Our findings may reflect a low baseline incidence of vitamin A deficiency in the study population and recent changes in the respiratory care of very low birth weight infants. The latter may have lessened the potential impact of vitamin A deficiency on lung disease. PMID- 1517922 TI - Early-onset group B streptococcal sepsis: a current assessment. AB - Group B streptococcus (GBS) is a common cause of early-onset sepsis in neonates. The most recent reviews describing incidence, diagnosis, treatment, and outcome evaluated data on patients from the early 1980s. To obtain current information about this disease, we retrospectively evaluated data on neonates with GBS early onset sepsis from nine hospitals in the United States between Jan. 1, 1987, and Dec. 31, 1989. There were 245 infants with GBS bacteremia identified among 61,809 live births, resulting in an incidence of 0.32%. Ninety-six infants (39%) were preterm (less than 38 weeks of gestational age). Maternal risk factors for infected preterm and term infants were similar. Antibiotics were administered during parturition in 10% of infants with bacteremia. Mothers of preterm infants received antibiotics up to 48 hours before delivery; mothers of term infants received antibiotics less than 4 hours before delivery. All preterm infants with bacteremia had symptoms; 22% of term infants with bacteremia had no symptoms. Group B streptococcal meningitis was confirmed in 6.3% of infants. Although 86% survived, GBS sepsis increased the birth weight-specific mortality rate up to eightfold in preterm infants and more than 40-fold in term infants. Although the incidence of GBS early-onset sepsis is not changing, we speculate that the improved birth weight-specific survival rate and the changing clinical presentation are due to improved intrapartum and neonatal management. PMID- 1517924 TI - Effects of type of dietary protein on acid-base status, protein nutritional status, plasma levels of amino acids, and nutrient balance in the very low birth weight infant. AB - STUDY OBJECTIVE: To determine the effect of the type of dietary protein (3.3 gm/kg per day) on acid-base status, protein nutritional status, plasma amino acid concentrations, and nutrient (nitrogen, fat, mineral, trace element) balance. SUBJECTS: Preterm infants (birth weight less than or equal to 1250 gm, gestational age less than or equal to 32 weeks) with no evidence of systemic disease, who had achieved a minimal enteral intake of 110 kcal/kg per day by 21 days of age. INTERVENTIONS: Each infant was fed three study formulas that differed only with respect to the ratio of whey to casein (60:40, 35:65, 18:82). Each formula was given for 1 week. At the end each week, blood was drawn and a 48 hour balance was determined. MAIN RESULTS: Late metabolic acidosis, uremia, and hyperammonemia were not observed. No differences in pH or serum bicarbonate were noted. Base excess was greater with the casein-predominant formula (18:82 greater than 35:65, 60:40) but remained within normal limits for the preterm infant. Plasma concentrations of threonine (60:40 greater than 35:65 greater than 18:82), phenylalanine, and tyrosine (18:82 greater than 35:65 greater than 60:40) differed. Nitrogen absorption (60:40 less than 35:65, 18:82), nitrogen retention (60:40 less than 35:65, 18:82), fat absorption (60:40, 35:65 greater than 18:82), and phosphorus absorption (60:40 less than 35:65, 18:82) also differed. CONCLUSIONS: At an intake of 3.3 gm/kg per day, the type of dietary protein had little effect on metabolic status. Differences in plasma amino acid concentrations and nutrient balance suggest that a formula containing protein with a whey/casein ratio of 35:65 may be preferable to that with a whey/casein ratio of 60:40 or 18:82 for the very low birth weight infant. PMID- 1517923 TI - Intravenous immune globulin therapy for early-onset sepsis in premature neonates. AB - Newborn infants may have IgG deficiencies that increase their susceptibility to bacterial infection. To determine whether intravenous immune globulin (IVIG) therapy improves survival rates in early-onset sepsis, we prospectively entered 753 neonates (birth weight 500 to 2000 gm, gestation less than or equal to 34 weeks, age less than or equal to 12 hours) into a multicenter, double-blind, controlled trial. Blood culture specimens were obtained and infants randomly assigned to receive 10 ml (per kilogram) intravenously of a selected IVIG (500 mg/kg) or albumin (5 mg/kg) preparation. Maternal and neonatal risk factors were not different between groups. Thirty-one babies (4.2%) had early-onset sepsis; the causative organisms were group B streptococcus (12 babies), Escherichia coli (6), and others (13). Of these 31 neonates, 7 (23%) died. Total serum IgG was higher for 7 days after IVIG therapy than after albumin treatment (p less than 0.05). During these 7 days, 5 (30%) of 17 albumin-treated and none of 14 IVIG treated patients died (p less than 0.05). The survival rate at 56 days of age, however, was not significantly improved. Group B streptococcus type-specific IgG antibody was significantly increased after IVIG treatment and appeared to be related to the amount of IVIG specific antibody. Infusion-related adverse reactions were less frequent in patients receiving IVIG therapy (0.5%) than in those receiving albumin. The IVIG therapy in neonates with early-onset sepsis, while reducing the early mortality rate, did not significantly affect the overall survival rate. Further studies are necessary to confirm these findings and to determine more effective therapeutic regimens. PMID- 1517925 TI - Mortality and morbidity rates among lower birth weight infants (2000 to 2500 grams) treated with extracorporeal membrane oxygenation. AB - To assess the validity of the currently accepted lower weight limit of 2 kg for treatment of neonates with extracorporeal membrane oxygenation (ECMO), we reviewed the outcome of lower birth weight (2.0 to 2.5 kg, n = 29) and higher birth weight (n = 235) for infants treated with venoarterial ECMO at our institution from 1984 through 1990. Newborn infants with congenital diaphragmatic hernia were not included. The mortality rate was significantly greater after venoarterial ECMO in lower than in higher birth weight infants (relative risk 3.45; confidence interval = (1.68, 5.79)). For infants with the diagnosis of respiratory distress syndrome, the mortality rate was 56% (5/9) for lower and 8% (2/25) for higher birth weight infants (p less than 0.01). The most frequent cause of death in lower birth weight infants was intracranial hemorrhage (7/10 deaths). The overall incidence of any neuroimaging abnormality was significantly greater for lower birth weight infants (p = 0.044), primarily because of the higher incidence of major intracranial hemorrhage. Finally, the risk of developmental delay (development quotient less than 70 at 1 to 2 years of age) among survivors available for follow-up was significantly higher among the lower than the higher birth weight infants. These outcome data suggest that further reduction of the current lower weight limit for ECMO should not become standard without prospective research or technologic advances. PMID- 1517926 TI - Cefpodoxime proxetil compared with amoxicillin-clavulanate for the treatment of otitis media. AB - In a multicenter, randomized, investigator-blinded trial, patients were randomly selected to receive either cefpodoxime proxetil or amoxicillin-clavulanate potassium orally for the treatment of acute suppurative otitis media. Patients were seen before, during, and at the end of therapy, and 2 to 3 weeks after completion of therapy. A total of 229 patients, 153 receiving cefpodoxime and 76 receiving amoxicillin-clavulanate were entered into the study; all patients were examined to determine drug safety. A total of 146 patients, 98 in the cefpodoxime group and 48 in the amoxicillin-clavulanate group, completed the study and were examined to determine drug efficacy. End-of-therapy microbiologic eradication rates in assessable patients were 92% for cefpodoxime and 86% for amoxicillin clavulanate (p = 0.14; 95% confidence interval (CI) on difference: -4.4%, 19.2%). End-of-therapy clinical response rates for assessable patients were as follows: cured, 68% for cefpodoxime and 65% for amoxicillin-clavulanate; improved, 24% for cefpodoxime and 23% for amoxicillin-clavulanate; and failed, 8% for cefpodoxime and 13% for amoxicillin-clavulanate (p = 0.57; 95% CI: -8.4%, 16.5%). Recurrence rates at long-term follow-up were 24% for cefpodoxime-treated patients and 25% for those given amoxicillin-clavulanate. Both drugs were well tolerated; 20.9% of those given cefpodoxime and 31.6% of amoxicillin-clavulanate-treated patients had drug-related adverse medical events (p = 0.102; 95% CI: -23.9%, 2.6%). Gastrointestinal complaints were the most frequently reported drug-related side effect in both groups: 11.8% of cefpodoxime-treated patients and 21.1% of those given amoxicillin-clavulanate (p = 0.076; 95% CI: -20.8%, 2.2%). Drug-related dermatologic side effects (e.g., diaper rash, pruritus, urticaria) were reported in 7.8% of cefpodoxime-treated patients and 14.5% of those who received amoxicillin-clavulanate (p = 0.160; 95% CI: -16.6%, 3.3%). Our findings suggest that clinical efficacy for cefpodoxime administered twice daily is equivalent to that of amoxicillin-clavulanate administered three times a day. PMID- 1517927 TI - Lack of effect of respiratory syncytial virus infection on theophylline disposition in children. AB - Conflicting reports raise a question about decreased plasma clearance (Clp) of theophylline in man during viral infections. Thus a dilemma exists concerning requisite dose adjustments. We examined this issue by retrospectively evaluating theophylline Clp in children infected with respiratory syncytial virus (RSV). Two pharmacokinetic approaches were applied to a one-compartment open model to fit theophylline concentrations during 83 hospitalizations of 76 children, 6 to 48 months of age, who received intravenous theophylline therapy and were tested for RSV infection. Iterative linear regression analyses of all theophylline data were used to estimate apparent volume of distribution, elimination rate constant, plasma half-life, and Clp in 39 of the hospitalizations. When insufficient data were available to distinguish apparent volume of distribution and elimination rate constant (n = 44), steady-state estimates of Clp were calculated. An age matched and percentile body weight-matched cohort design presented RSV as the primary covariate. Theophylline Clp was similar in 29 matched RSV-infected and uninfected pairs (1.32 +/- 0.14 and 1.25 +/- 0.05 ml/kg per minute, respectively), as were other pharmacokinetic values. Unexpectedly, a significant, inverse linear relationship was found for Clp and percentile body weight. Additionally, children born prematurely and hospitalized in the neonatal intensive care unit had significantly higher theophylline Clp; this did not affect findings regarding RSV infection. Theophylline Clp was not decreased in RSV-infected children. Current theophylline dosing recommendations for young children infected with RSV should not be altered, but careful monitoring of plasma theophylline levels should be continued. PMID- 1517928 TI - Management of neonatal Graves disease with iopanoic acid. AB - An infant with thyrotoxicosis whose mother had Graves disease was treated with sodium iopanoate. Euthyroid status was achieved rapidly and maintained with minimal effort in comparison with the conventional multidrug regimen. There were no toxic effects, and hypothyroidism did not occur. PMID- 1517929 TI - Double-blind, controlled trial of short-term prednisone therapy in immunoglobulin A glomerulonephritis. AB - Twenty children and adolescents with IgA glomerulonephritis were enrolled in a crossover trial. Each received 12 weeks of prednisone therapy and 12 weeks of placebo dosing. Urinary protein and erythrocyte excretion were monitored during both courses. There was no evidence that, under the conditions of the study, corticosteroid therapy was effective in IgA nephropathy. PMID- 1517930 TI - Effect of long-term calcitonin therapy by injection and nasal spray on the incidence of fractures in osteogenesis imperfecta. AB - The effect of calcitonin therapy by injection or nasal spray on the incidence of bone fractures was studied in patients with osteogenesis imperfecta. In contrast to injection of calcitonin, intranasal administration of calcitonin twice a week for 2 weeks, followed by 2 weeks of no therapy, was simple and seemed beneficial for decreasing bone fractures in patients with osteogenesis imperfecta. PMID- 1517931 TI - Tibia vara: a complication of adolescent obesity. AB - Tibia vara is characterized by inhibited growth of the medial portion of the proximal tibial growth plate, leading to progressive bowleg deformity. Twenty nine adolescent patients with this condition were reviewed: all were black, 27 (93%) were male, and 19 (66%) had only one side affected. Progressive deformity rather than knee discomfort was the most common presenting complaint. The deformity reportedly developed rapidly during the adolescent growth spurt. The body weights of these patients exceeded the 95th percentile for age and gender by an average of 43 kg. The absence of significant symptoms and a body habitus that obscured the deformity often resulted in delayed diagnosis. Physicians involved in the care of obese black male adolescents should carefully examine them for tibia vara, which has a reported prevalence of 2% to 3% in this population. Treatment options are severely restricted if the condition is not diagnosed early. PMID- 1517933 TI - Unforgettable patients. PMID- 1517932 TI - Recurrent genitourinary chlamydial infections in sexually active female adolescents. AB - To determine the recurrence rate of chlamydial infections, we initially screened an urban population of 1308 sexually active female adolescents for chlamydial infection at the urethral and endocervical sites; these young women were followed and had additional examinations for infection. Chlamydial infection was documented by tissue culture in 31.1% (407) of them at some time during the study. After appropriate antibiotic treatment, 68.3% (278/407) returned for test of-cure cultures within 3 months of their initial infection; of those 278, a total of 254 had sterile cultures. These patients were followed to determine the recurrence rate of chlamydial infections. Of these 254 patients, 177 (69.7%) had one or more follow-up visits; 38.4% (68/177) had a recurrent chlamydial infection. The majority of recurrent infections were documented within 9 months of the initial infection. Recurrent infections with the same serovar were frequent, suggesting reinfection by untreated partners or possible relapse of the initial chlamydial infection. This high rate of recurrent infection suggests that female adolescents should be rescreened frequently for genitourinary chlamydial infections. PMID- 1517934 TI - Neonatal screening for glucose-6-phosphate dehydrogenase deficiency. PMID- 1517935 TI - Management of neonatal sepsis. PMID- 1517936 TI - "Parental nose blowing": another oropharyngeal custom. PMID- 1517937 TI - Screening for high serum cholesterol concentrations in children. PMID- 1517938 TI - Multiple-lumen umbilical venous catheters. PMID- 1517939 TI - Multiple-lumen umbilical venous catheters. PMID- 1517940 TI - Seizures during theophylline therapy. PMID- 1517941 TI - Short bowel syndrome. AB - With utilization of the techniques discussed in this review, patients with short bowel syndrome can be expected to live prolonged lives, even after fairly massive resection. Advances in parenteral and home parenteral nutrition and changes in the long-term management of chronic complications have altered the lifestyles of patients with short bowel syndrome. Intestinal transplantation may become an effective mode of therapy within a short period of time. Many surgeons faced with the possibility of leaving a child with only 10-15 cm of bowel in the past have closed the abdomen with the dead bowel and let the child die. These recent advances raise interesting ethical dilemmas. Research into the process of intestinal adaptation as well as greater experience with intestinal transplantation and other modes of therapy may further improve prognosis. PMID- 1517942 TI - Ultrasonography and gastric emptying: evaluation in infants with gastroesophageal reflux. AB - We have applied ultrasonography to the evaluation of gastric emptying in children. Two different populations have been investigated: normal children and children with gastroesophageal reflux. All the patients were less than 6 months of age. The diagnosis of gastroesophageal reflux was defined by 24-h pH measurement. The technique, used to measure gastric emptying, is the one described by Bolondi et al. In this research we used the simplified method. All children had been submitted to the examination after 4-h fasting. The standard meal was the usual milk formula, 300 ml/m2 body surface area (BSA). A cross section area of the gastric antrum was determined before a meal and every 15 min for 2 h. The examination was concluded after two measurements were equal to the basal one. The normal gastric emptying curve was determined by a control group. Patients with gastroesophageal reflux showed three different kind of gastric emptying: (a) normal gastric emptying in 20% of cases, (b) abnormal gastric emptying in 15% of cases, and (c) intermediate cases in which the plateau curve is abnormal but the end time of gastric emptying is normal. We defined these three kinds of curves as type I or normal, type III or abnormal, and type II or intermediate. The estimate of frequency in patients with gastroesophageal reflux is similar to the reported data of the literature. PMID- 1517943 TI - Efficacy of domperidone in infants and children with gastroesophageal reflux. AB - This study sought to define the therapeutic efficacy of domperidone in infants and children with gastroesophageal reflux. A double-blind, placebo-controlled trial was performed in seventeen children (ages 5 months to 11.3 years) with moderate to severe gastroesophageal reflux who had not responded to standard nonpharmacological therapy. Subjective and objective measures (weight gain, esophageal pH probe study, radionuclide gastric emptying scan) of gastroesophageal reflux were evaluated. Therapy with domperidone for 4 weeks was effective only in reducing the total number of reflux episodes in the two-hour postprandial period (p less than 0.01); however, it did not result in symptomatic improvement or significant improvement in other measures of gastroesophageal reflux or gastric emptying. After therapy for 8 weeks symptomatic improvement was reported in some patients who had denied improvement after 4 weeks of therapy, suggesting that more than 4 weeks of therapy may be required for some patients to obtain a clinical response. Mild self-limited diarrhea was reported by six patients (four domperidone, two placebo). We conclude that domperidone is tolerated by most infants and children with gastroesophageal reflux; however, 4 weeks of therapy was only minimally effective in producing objective improvement of gastroesophageal reflux and did not result in symptomatic improvement. Further studies of longer duration are needed to resolve the question raised by this study: that domperidone may be beneficial for patients with gastroesophageal reflux when given for more than four weeks. PMID- 1517944 TI - Effect of diosmectite on intestinal permeability changes in acute diarrhea: a double-blind placebo-controlled trial. AB - The effect of diosmectite on intestinal permeability changes in acute diarrhea was measured during a double-blind placebo-controlled trial carried out in 59 Gabonese children aged 5-35 months. Intestinal permeability tests (IPTs), measuring the urinary elimination of orally administered lactulose and mannitol at a dosage of 1 g/10 kg each, were performed during the morning following admission and repeated 2 days later after treatment by diosmectite or placebo. During the first IPT, urine volume and lactulose and mannitol urinary recoveries were comparable in the diosmectite and in the placebo groups: 50 vs. 35.5 ml (median; p = 0.21), 1.01 vs. 1.27% (p = 0.35), and 2.20 vs. 2.87% (p = 0.12). As a result, the lactulose/mannitol (L/M) ratio was similar in the two groups: 44.44 vs. 35.33% (p = 0.98). During the second IPT, the urinary lactulose recovery decreased similarly in both groups (-0.18 vs. -0.29%; p = 0.76), whereas the urinary mannitol recovery exhibited opposite variations, the increase in the diosmectite group (+ 1.43%) contrasting significantly with the decrease in the placebo group (-0.47%; p = 0.01). When comparing the first and the second IPT, the decrease of the L/M ratio was significant in the diosmectite group (44.44 vs. 28.32%; p = 0.02) and not in the placebo group (35.33 vs. 48.23%; p = 0.91). During gastroenteritis, diosmectite appears to enhance absorption of mannitol, a marker of intestinal absorptive area. PMID- 1517945 TI - Helicobacter pylori infection in children: clinical, endoscopic, and histologic correlations. AB - We have assessed 270 consecutive patients (age range 0.8-20 years) referred for endoscopic study because of abdominal pain during 32 months. Helicobacter pylori (HP) was detected by culture in 91 cases (33.7%). HP colonization increased significantly with age (p less than 0.01). Nine patients less than 5 years of age were colonized by HP. A previous history of peptic ulcer disease in first-degree relatives was significantly more frequent in the HP-positive group (p less than 0.001). The frequency of HP positiveness as related to diagnosis was: normal, 3.3%; nonactive chronic gastritis, 100%; active chronic gastritis, 97.2%; gastric ulcer, 75%; and duodenal ulcer, 90.9% (p less than 0.001). Endoscopic nodular antritis was a frequent (67%) and specific finding; this presence was associated with that of lymphoid follicles in the histopathological study. Signs of histological activity were observed in 55.9% of the HP-positive patients. The histological colonization by HP was assessed semiquantitatively, and a significantly greater HP colonization score was observed in patients with signs of histological activity (p less than 0.001). A significant correlation was found between HP colonization score and histological score (rs = 0.574), with a significant association between the degree of HP colonization and the histologic categories (p less than 0.001). The present study suggests a pathogenic role of HP in the development of gastroduodenal disease in children. PMID- 1517946 TI - Neonatal cholestasis, hypoglycemia, and congenital hypopituitarism. PMID- 1517947 TI - Hepatitis B virus DNA in liver tissue of chronic HBsAg carriers in childhood and its relationship to other viral markers. AB - The aim of the study was to examine the state of hepatitis B virus (HBV) DNA in liver tissue of 103 children with chronic hepatitis B aged 0.5-18 years to detect free and integrated viral sequences by Southern blot hybridization. HBV DNA was found in 74 patients. Seventy-two were seropositive for hepatitis B e antigen (HBeAg) and two had anti-HBe antibodies. Integrated sequences could be demonstrated in two children. One of them had only integrated HBV DNA and was anti-HBe seropositive. The other one presented both free and integrated viral sequences and developed seroconversion from HBeAg to anti-HBe 5 months after biopsy. In 29 hepatitis B surface antigen (HBsAg) carriers, no HBV DNA could be detected in the liver. Ten were HBeAg and 19 anti-HBe seropositive. HBV DNA in serum was found in 65 of the 74 Southern blot-positive and only in two cases of the Southern blot-negative patients. In conclusion, most of the HBeAg-positive children had free HBV DNA in their liver tissue and all patients with anti-HBe except one were negative. According to our results, HBV DNA integration into the liver cell genome can occur at an early stage of chronic disease but is not a frequent event. PMID- 1517948 TI - Serum primary bile acids in the course of celiac disease in children. AB - Serum concentrations of primary bile acids (BAs) were determined in the course of celiac disease and in healthy age-matched controls. Determinations of BAs were made by radioimmunoassays after an overnight fasting and for 4 h postprandially after intake of a standardized test meal. In untreated celiac disease presenting with subtotal villous atrophy, peak concentrations of primary BAs were significantly delayed and serum levels were significantly higher than in controls. Small but significant abnormalities persisted after a period of gluten free diet despite a normalization of mucosal morphology. Slightly pathological standard liver function tests in five patients were related to increased fasting levels but not to the postprandial pattern of BAs, indicating that the observed abnormalities postprandially were not related to liver disease. Further studies simultaneously focusing on deconjugation mechanisms, absorption, and pool sizes of BAs are required to explain the postprandial BA pattern under the course of celiac disease. PMID- 1517949 TI - Milk protein quality in low birth weight infants: effects of protein-fortified human milk and formulas with three different whey-to-casein ratios on growth and plasma amino acid profiles. AB - Growth rates (weight, length, and head circumference) and selected biochemical indexes of protein metabolism (serum urea, acid-base status, and plasma amino acid concentrations) were determined in low birth weight (LBW) infants appropriate for gestational age (birth weight less than 1,650 g) fed three formulas differing only in the whey-to-casein ratios: 60/40, 50/50, and 35/65. A group of infants fed exclusively human milk protein (HMP)-fortified human milk was used as a control. All diets provided similar daily protein and energy intakes, which were 3.5 g/kg and 122 kcal/kg in the human milk-fed infants and 3.3 g/kg and 121 kcal/kg in the formula-fed infants. Neither weight gain nor rate of growth in length and head circumference differed between the feeding groups and reached intrauterine or better rates in all groups. Values for serum urea and acid-base status were normal and also did not differ among the groups. At the end of the study, plasma threonine concentrations were significantly higher in all formula-fed infants than in the infants fed human milk. The highest plasma threonine concentration was found in the infants receiving the whey-predominant formula. Plasma concentrations of valine, methionine, and phenylalanine were also significantly higher in all formula-fed groups when compared with the human milk group. Plasma total essential amino acid concentrations were also significantly higher in the formula-fed infants than in the human milk fed. The results show that protein quality does not affect growth rate or biochemical indexes of metabolic tolerance in LBW infants fed adequate protein and energy intakes.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1517950 TI - Tryptophan fortification of adapted formula increases plasma tryptophan concentrations to levels not different from those found in breast-fed infants. AB - Several recent studies have demonstrated significantly lower plasma total tryptophan concentrations in formula-fed than in breast-fed infants. We have measured preprandial plasma amino acid concentrations in infants breast-fed or fed a formula with a protein concentration of 1.57 g/dl and with a whey/casein ratio of 60:40 or a formula with a protein concentration of 1.37 g/dl and a whey/casein ratio of 40:60 and fortified with 10 mg/dl (15 mg/100 kcal) of tryptophan. Healthy term infants (10 per group) were either breast-fed from birth or randomly assigned to one of the two study formulas. At 4 and 12 weeks of age, anthropometric measurements were performed and blood samples were obtained. During the study period of 12 weeks, all infants showed normal growth (weight, length, and head circumference) and there were no statistically significant differences between the groups. The plasma concentrations of the essential amino acids phenylalanine, threonine, valine, and lysine were significantly lower in the breast-fed group than in both formula-fed groups. For tyrosine, methionine, leucine, histidine, isoleucine, and arginine, no significant differences could be found between the feeding groups. Concentration of total plasma tryptophan was significantly higher in the breast-fed group than in the group fed the tryptophan unfortified formula, but no statistically significant difference could be found between the plasma tryptophan concentration in the breast-fed group versus the group fed the tryptophan-fortified formula. The results indicate that tryptophan fortification of adapted formula is necessary to achieve plasma total tryptophan concentrations similar to those found in breast-fed infants.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1517951 TI - Gastroesophageal reflux: clinical presentation in two pairs of twins. PMID- 1517952 TI - A case of Caroli's disease with special reference to hepatic CT and US findings. PMID- 1517953 TI - A standardized protocol for the methodology of esophageal pH monitoring and interpretation of the data for the diagnosis of gastroesophageal reflux. Working Group of the European Society of Pediatric Gastroenterology and Nutrition. PMID- 1517954 TI - Genetic aspects of disorders in beta-lipoproteins. PMID- 1517955 TI - Possible alleviation of atopic eczema in a breastfed infant by maternal supplementation with a fish oil concentrate. PMID- 1517956 TI - Development of pulmonary fibrosis in mice during infection with Paracoccidioides brasiliensis conidia. AB - Pulmonary fibrosis is a feared sequelae of paracoccidioidomycosis. We sought to determine if mice exposed to Paracoccidioides brasiliensis conidia would develop pulmonary fibrosis. BALB/c mice were infected intranasally with P. brasiliensis conidia and sacrificed at regular intervals. One lung was sectioned for histopathology and sections were stained with haematoxylin and eosin, trichromic and argentic stains; the other lung was homogenized and cultured to determine the viability of the fungus. One week post-challenge, only small peribronchial foci were apparent. After 4 weeks, reticular fibres appeared disorganized and disrupted. Six to 8 weeks later peribronchial infiltrates were larger and appeared surrounded by reticular fibres; thick collagen I fibres were noticed in the infiltrated areas at this time. On weeks 10-12, infiltrates were confluent and reticular fibres were concentrated around the inflammatory foci; collagenization was apparent. Observations up to 16 weeks revealed diffuse involvement of the lung parenchyma with extensive collagenization. Lung cultures were always positive. We suggest that inhalation of P. brasiliensis conidia induces adverse lung responses leading to changes in the proportion of collagen fibres I and III. PMID- 1517957 TI - Effects of calcium ions on the germination of Sporothrix schenckii conidia. AB - Sporothrix schenckii conidia were induced to germinate in varying concentrations of added calcium. Calcium had a stimulatory effect on the process and a calcium concentration of 1 mM was found to be optimal. Measurements of radioactive calcium uptake confirmed that uptake was taking place during the germination of conidia to the mycelial form of the fungus. Three calcium uptake peaks were observed, the first occurred 10 min after inoculation and the other two peaks coincided with the first 2 cycles of DNA synthesis in these cells. Ionophore A23187 and cobalt sulfate inhibited germination of S. schenckii conidia and altered the normal calcium uptake pattern in these cells. On the other hand, phorbol 12-myristate-13-acetate, a stimulator of protein kinase C (PKC) activity, stimulated germination in medium without calcium. This suggests that PKC activation might account for the germination of conidia in the absence of added calcium. The effects of increasing the calcium concentration on RNA and protein synthesis were also studied. A stimulation of RNA synthesis was found at all times tested with maximum stimulation 6 h after inoculation. A stimulation in protein synthesis was also observed but only after 12 h incubation. PMID- 1517958 TI - Synergistic postantifungal effect of flucytosine and fluconazole on Candida albicans. AB - The in vitro efficacy of flucytosine and fluconazole, separately and in combination, with respect to induction of a postantifungal effect (PAFE) on Candida albicans was studied. PAFE refers to the persistent suppression of fungal cell growth following a short period of exposure to an antifungal agent. A turbidometric method was used to measure cell growth and to quantitate the PAFE following exposure of C. albicans yeast cells to different concentrations of the two agents for 2 h. The PAFE was determined by the difference in time (h) required for growth of the control and test cultures to increase to the 0.5 absorbance level following removal of the drug by dilution. Minimum (MIC) and fractional inhibitory concentration determinations were made and the data used for selecting the concentrations used in the PAFE evaluations. A synergistic interaction of the two drugs at concentrations well below their individual MICs was evidenced. Flucytosine:fluconazole ratios of 1:16-1:32 at concentrations ranging from 0.024-0.098 micrograms ml-1 and from 0.78-1.56 micrograms ml-1, with flucytosine and fluconazole, respectively, induced PAFEs which persisted for 2.5 h longer than those achieved when each of the two agents was assayed separately. PMID- 1517959 TI - Fatal systemic candidiasis of gastrointestinal origin: an experimental model in mice compromised by anti-cancer treatment. AB - An experimental model of fatal systemic candidiasis originating from the gastrointestinal (GI) tract of compromised mice is presented. ICR female mice were compromised by a single anti-cancer treatment: irradiation (4 or 6 Greys i.e. 400-600 rads), methotrexate (MTX) (3 mg per mouse, intraperitoneally) or 5 fluorouracil (5FU) (200 mg kg-1, intravenously). Three days later, compromised and non-treated control mice were exposed to Candida albicans administered orally. Morbidity and mortality due to candidiasis were monitored for 30 days post-candidal inoculation. Increased and longer GI colonization was noted among the MTX and 5FU treated mice, or 6 Greys irradiated mice (up to 92.3% for over 30 days in anti-cancer treated mice). The stomach was found to be the major part of the GI tract involved in fungal colonization. A significant number (53.8-83.3%) of the anti-cancer treated mice developed systemic candidiasis originating from the GI tract, which was fatal in 30-80% of the infected animals. In systemically infected animals, candidal antigen was demonstrated in the serum, and fungal abscesses containing C. albicans were observed in the liver, kidneys and spleen. C. albicans was isolated from the infected organs. The severity of the infection, as reflected by the number of fungi in visceral organs, and by mortality during the 30 days post-candidal inoculation, indicated differences in the course and nature of the infection among the three treatment groups (i.e. MTX, 5FU, 6 Greys).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1517960 TI - Disseminated African histoplasmosis in a Congolese patient with AIDS. AB - We report the first Congolese case of African histoplasmosis in a patient with AIDS which represents the third case to be described in the literature. This contrasts with the now frequent occurrence of Histoplasma capsulatum histoplasmosis in HIV-infected subjects in North America; the difference is likely to be due to differences in exposure to the fungus rather than to differences in behaviour of the fungus or in the epidemiology of HIV. PMID- 1517961 TI - Coccidioides immitis presenting as a mycelial pathogen with empyema and hydropneumothorax. AB - A previously healthy Caucasian male developed hydropneumothorax and a pleural peel filled with pleomorphic, septate hyphae. The only organism grown from cultures of the lung and pleural fluid was Coccidioides immitis, confirmed by exoantigen testing. Spherule-endospore forms were produced, however, following injection of the arthroconidial tissue isolate into BALB/c mice. The patient had a positive immunodiffusion complement-fixation test and developed a positive coccidioidin skin test during therapy. He recovered following thoracotomy and wedge resection of the ruptured coccidioidal cavity, and therapy with amphotericin B followed by fluconazole. The sole presence of the mycelial form of the dimorphic fungus C. immitis in the pleural space may have been due to a low CO2 partial pressure at that site secondary to a bronchopleural fistula. The case shows a distinctive and uncommon presentation of coccidioidomycosis which demonstrates the specificity of both the immunodiffusion complement-fixation assay in diagnosing this disease and the exoantigen test in confirming culture results. PMID- 1517962 TI - The source of the growth-promoting factor(s) affects the plating efficiency of Paracoccidioides brasiliensis. AB - We studied the influence of the growth factor (GF) source, concentration and production time on the plating efficiency of Paracoccidioides brasiliensis yeast cells. The highest plating efficiencies were achieved when the GF was derived from a fast growing P. brasiliensis isolate which was not homologous to the plated samples. PMID- 1517963 TI - Sulfonic acid dyes: inhibition of the human immunodeficiency virus and mechanism of action. AB - Over 50 different commercially available sulfonic acid-containing dyes were analyzed for their ability to prevent HIV-1-induced cell killing and in inhibiting HIV-1 replication. Compounds of remarkably similar structure, but with differing patterns of sulfonic acid group substitutions, had a wide range of potency in inhibiting HIV-1. Chicago sky blue (CSB) was highly effective in the inhibition of HIV-1 with less toxicity to CEM-SS cells than most of the other sulfonated dyes tested. Synthesis of CSB was undertaken to produce a product greater than 98% pure and this compound was used to elucidate the possible mechanisms by which this class of structurally related compounds inhibits HIV-1. Addition of CSB to cells infected at high multiplicity at any time up to 24 h after infection, unlike dideoxycytidine (ddC) or oxathiin carboxanilide (OC), inhibited HIV-1-induced cell killing. Other postinfection time course studies revealed that CSB had to be present for 24 h or longer immediately after infection to be protective. Virus binding to cells occurred in the presence of CSB, but the requirement for virion envelope-cell membrane fusion was delayed. CSB was a potent inhibitor of the reverse transcriptase (RT) of both HIV-1 and HIV-2, although it was less active against HIV-2 in a cell killing-based assay. CSB also inhibited Rauscher and LP-BM5 murine leukemia viruses. CSB appears to disrupt the interaction between viral proteins and cell membranes, both in the fusion step early in the infection cycle and in the development of syncytia in the late stages of virus infection. PMID- 1517964 TI - Predictors of HIV-1 disease progression in early- and late-stage patients: the U.S. Army Natural History Cohort. Military Medical Consortium for Applied Retrovirology. AB - HIV-infected individuals in both early and late stages of HIV disease were evaluated over 2 years to assess temporal trends and determinants of disease progression. The Walter Reed (WR) staging system was used to categorize patients into an early-stage cohort (WR Stages 1 and 2, N = 1183) and a late-stage cohort (WR Stage 5, N = 260) based on the initial clinical evaluation. Progression was defined as the occurrence of Stage 5 disease or beyond for the early cohort and Stage 6 disease or beyond for the late cohort. The cumulative incidence of progression was 15.7% (137 events) for the early-stage cohort, and 53.7% (85 events) for the late-stage cohort. Baseline CD4+ T lymphocyte (T4) count was the most significant marker of progression: 26% of WR Stage 1 or 2 patients with T4 lymphocytes below 500/mm3 progressed, compared with 12% with T4 lymphocytes at or above 500/mm3. In late-stage individuals, 83% with T4 lymphocytes under 200/mm3 progressed, compared with 27% with T4 lymphocytes at or above 200/mm3. Older age was associated with progression in both early- and late-stage groups. Differences in the rates of disease progression were not significant between blacks and whites or between men and women. Two-year rates of progression among the late stage patients dropped from 78 to 47% between 1986 and 1988. This contrasted with progression rates in the early-stage cohort, which remained stable: 18% for those entering follow-up in 1986 and 17% for those entering follow-up in 1988. These data indicate a significant slowing of HIV disease progression rates and mortality rates among individuals with late-stage disease that is temporally associated with the increased availability and use of therapies. With control of T4 lymphocyte count, age, and calendar time, neither gender nor race was significantly associated with progression in either early- or late-stage patients. PMID- 1517965 TI - HIV infection in American Indians and Alaska Natives: surveys in the Indian Health Service. AB - A network of surveys of HIV seroprevalence in American Indians and Alaska Natives (AI/AN) was begun in 1989. From July 1, 1989 through June 30, 1991, 37,681 serologic specimens were collected from prenatal and sexually transmitted disease patients in 58 facilities operated or funded by the Indian Health Service. Specimens from AI/AN women receiving initial prenatal care showed an overall HIV prevalence of 0.3/1,000, while specimens obtained during the third trimester of pregnancy showed an overall prevalence of 1.0/1,000. The rate for rural third trimester prenatal patients (0.9/1,000) was similar to that for urban patients (1.1/1,000). HIV rates among third trimester AI/AN patients in three western states were 4 to 8 times higher than rates observed in childbearing women of all races in those states. The overall HIV seroprevalence in AI/AN seeking care for sexually transmitted diseases was 4.5/1,000 for males (urban 10.8/1,000; rural 2.0/1,000) and 0.7/1,000 for females (urban 0.9/1,000; rural 0.6/1,000). Approximately 1,210 to 4,250 (midpoint of range = 2,730) AI/AN in the U.S. are projected from survey findings to be currently infected with HIV. The presence of HIV in multiple specimens from rural areas and the similarity of HIV infection rates for female patients from rural and urban locations provides evidence of diffusion of the HIV epidemic to rural AI/AN, and emphasizes the need for effective HIV prevention for this population. PMID- 1517966 TI - HTLV-I DNA sequences in CNS tissue of a patient with tropical spastic paraparesis and HTLV-I-associated myelopathy. AB - Human T cell lymphotrophic virus type I (HTLV-I) is the etiologic agent of adult T cell lymphoma/leukemia (ATLL) and tropical spastic paraparesis/HTLV-I associated myelopathy (TSP/HAM). We studied an HTLV-I-seropositive, white man diagnosed in 1977 with ATLL and 10 years later, 6 months prior to his death, with TSP/HAM. Sections of brain, spinal cord, and visceral tissues were examined histologically, immunohistochemically, by in situ hybridization, and by the polymerase chain reaction (PCR). PCR amplification of a region of the polymerase (pol) gene of HTLV-I from visceral tissue demonstrated the presence of proviral HTLV-I DNA in paraffin-embedded sections from the liver and in DNA extracted from frozen sections of kidney and spleen, but failed to demonstrate viral sequences in paraffin sections of the lung and a lymph node. PCR analysis of CNS tissue demonstrated viral sequences in regions of the brain including frozen samples from cerebellum and cerebral cortex and paraffin sections of the thoracic spinal cord, but failed to detect proviral DNA in sections from a region in the lumbar cord. These results map the distribution of HTLV-I DNA sequences in the CNS of a patient with TSP/HAM for 3 months. PMID- 1517967 TI - Envelope-specific antibodies in the saliva of individuals vaccinated with recombinant HIV-1 gp160. AB - HIV-1-specific antibodies have been detected in the saliva of seropositive individuals and may play a role in preventing oral transmission of the virus. We have analyzed saliva samples obtained from HIV-1-seronegative individuals who were immunized with various dosages of a recombinant HIV-1 envelope glycoprotein (gp160) vaccine for the presence of antibodies to HIV-1. Antibodies specific for envelope glycoproteins were detected in saliva from all of the volunteers, with those vaccinated with the higher doses of 640 and 1,280 micrograms showing the strongest responses. Peak salivary antibody titers were obtained 4-14 weeks after vaccination; they then gradually dropped in parallel with serum antibody titers. These envelope-specific antibodies were detected in whole saliva and in submandibular saliva but not in parotid saliva, suggesting that the source of antibodies in saliva is from serum transudation. The class of reactive antibodies was found to be IgG. The HIV-1-specific antibodies in the saliva of vaccinated individuals may offer local protection against HIV-1 infection. PMID- 1517968 TI - HIV detection in culture of peripheral blood mononuclear cells: a relevant in vitro correlate of the antiviral effect of ZDV in vivo. AB - To better assess the antiviral effect of zidovudine (ZDV) in vivo and understand its limitations, we have studied human immunodeficiency virus (HIV) replication in peripheral blood mononuclear cell (PBMC) cultures from 25 ZDV-treated patients and 20 untreated controls. Three months after initiation of therapy, 9 of the 25 treated cases became negative for HIV isolation (36%). Untreated cases never converted to a negative culture. In patients treated by ZDV and who remained culture positive, the kinetics of HIV replication in PBMC culture was found to vary with time. A statistically significant delay in the production of HIV in PBMC cultures from treated cases could be demonstrated after 3 months of ZDV therapy, when compared with untreated patients. By contrast, in such untreated patients the time required to reach the peak of reverse transcriptase activity in culture decreased during the follow-up period. These changes of in vitro HIV replication kinetics as well as the change to negative culture during ZDV therapy probably reflected the reduction of the number of infected cells in vivo. These results as well as the decrease of p24 antigenemia do indicate that ZDV indeed inhibits HIV replication in vivo. However, the effect of ZDV on HIV replication kinetics in PBMC fails to reach significance at 6 months, suggesting that the antiviral effect of ZDV may decrease over time. Our results suggest that ZDV is most effective when the intensity of HIV replication in vivo is still low. PMID- 1517969 TI - Family physician attitudes about HIV screening. AB - This study examined why and for whom family physicians are likely to require HIV screening according to general policies or procedures, based on a national survey of 2,660 family practice physicians. Of those contacted, 1,678 responded, yielding a response rate of 63.7%. The study also examined whether attitudes toward screening differed for physicians in different types of practices, of varying educational backgrounds, and with differing opinions regarding treating persons with AIDS (PWAs). The results showed that required screening was most strongly endorsed for pregnant women who had other risk factors and for i.v. drug users. Those physicians who most favored mandatory screening were also most likely to favor the mandatory reporting of AIDS cases to public health officials. They also had the least formal medical training (were not residency trained or board certified) and expressed the greatest apprehension regarding their own and their staff's preparedness and willingness to treat PWAs. A major implication of the findings is that family physicians and others who do mandatory testing should be provided opportunities, through residency training, board-certification preparation, or continuing medical education, to learn how to care for those patients they test who turn out to be seropositive. PMID- 1517970 TI - Recombinant human erythropoietin and the treatment of anemia in patients with AIDS or advanced ARC not receiving ZDV. PMID- 1517971 TI - Giant esophageal ulcer treated with steroids in AIDS patient. PMID- 1517972 TI - The association of needle cleaning with reduced seroprevalence among intravenous drug users sharing injection equipment. PMID- 1517973 TI - Epidemiology of HIV-1 infection in bisexual women. PMID- 1517974 TI - [Synthesis of 1-trans-cinnamoyl- and 1-[trans-3-(pyridyl)acryloyl]-2 pyrrolidinone derivatives and their effect on hemicholinium-induced impairment of water maze learning in mice]. AB - Various 1-trans-cinnamoyl-2-pyrrolidinones (6a-k) and 1-[trans-3 (pyridyl)acryloyl]-2-pyrrolidinones (9a-c) were prepared as analogues of the notropic agent, aniracetam (2), and their effects on hemicholinium-induced impairment of water maze learning in mice were examined. 1-(trans-3 Methoxycinnamoyl)-, 1-(trans-4-methoxycinnamoyl)- and 1-(trans-4-chlorocinnamoyl) 2-pyrrolidinones (6c, d, h) and 1-[trans-3-(3-pyridyl)acryloyl]-2-pyrrolidinone (9c) were found to be more active than aniracetam in these tests. In addition, these 2-pyrrolidinones (6a-k, 9a-c) were apparently observed to lengthen mouse survival time following hemicholinium injection into the brain. PMID- 1517975 TI - [Protective effects of the fractions extracted from the callus of Acer nikoense Maxim. on alpha-naphthylisothiocyanate induced liver injury]. AB - It has been reported that the methanol extract from the bark of Acer nikoense MAXIM. (AN) and the fractions separated from this extract showed the protection for liver injuries induced by carbontetrachloride (CCl4) in rat. On the other hand, the evidence manifested that the fractions of the callus of young branches from AN were recognized to have protective effects on the CCl4-induced liver injuries in rat. In this study, the protective activities of the fractions extracted from the callus of AN were investigated on the alpha naphthylisothiocyanate (ANIT)-induced liver injuries in rat. The protectively active principles on the ANIT-induced liver injuries were found in the ether soluble fraction. The components of the protective effect were purified by repeated silica gel chromatographies. One of the protective substances in this fraction was identified to be beta-sitosterol. The protective fractions on the ANIT-induced liver injuries showed the protective effects on ANIT-induced cholestasis, but did not show cholagogic effects. PMID- 1517976 TI - [Antipyretic effects of traditional Chinese medicines in bacterial endotoxin induced febrile rabbits]. AB - The antipyretic effects of oral administration of eight traditional Chinese medicines (dried extracts) were tested in febrile rabbits injected with bacterial pyrogen, lipopolysaccharide (LPS) 0.05 micrograms/kg (i.v.). The traditional Chinese medicines were given 0.6-2 g/10 ml/kg (p.o.) simultaneously with LPS. The most potent antipyretic effect was observed in Dai-jyoki-to (Ta-chen-chi-tang). The moderate antipyretic effects were observed in Toki-syakuyaku-san (Tang-kuei shao-yao-san) and Syo-saiko-to (Hssiao-chai-hu-tang). Koso-san (Hsiang-su-san), Oren-gedoku-to (Huang-lien-chieh-tu-tan), Gorei-san (Wu-ling-san), Kakkon-to (Ko ken-tang) and Byakkoka-ninjin-to (Pai-hu-chia-jen-sheng-tang) showed no effects. PMID- 1517977 TI - [The depression of hepatic drug-metabolizing enzyme activity in rats with carrageenan-induced inflammation. II. The effect on the status of plasma antipyrine concentration in rats]. AB - The variation of hepatic drug-metabolism was investigated in male Wistar rats bearing hind paw edema induced by carrageenan (1%, 0.1 ml, s.c.). The content of cytochrome P-450 and the biotransformation of aminopyrine in the hepatic 9000 x g supernatant (S-9) decreased after the subcutaneous injection of carrageenan to rat hind paw. In carrageenan-treated rats the plasma concentration of antipyrine after the administration of antipyrine (20 mg/kg, i.v.) was higher than that of control rats. In comparison with the control groups, the pharmacokinetic parameters of antipyrine in carrageenan-treated rats was altered. AUC0-200 and t 1/2 significantly increased and CLtot and ke significantly decreased. On the other hand, no change of the volume of distribution (Vd) was observed. The results indicate that the hepatic drug metabolism under the carrageenan-induced inflammation is inhibited both in vitro and in vivo. PMID- 1517978 TI - [Determination and stability studies of urea in urea creams by high-performance liquid chromatography]. AB - A method was developed for determining urea in urea creams by high-performance liquid chromatography using strong acidic cation exchange gel. Elution was carried out with 0.05 M phosphate buffer (pH 3.4) at 40 degrees C, and detection was made with a UV-spectrometer at 200 nm. This method was used for studying and comparing the stability of urea creams produced by ourselves and by other manufactures. The assay showed that there were differences in the stability of the tested creams. PMID- 1517979 TI - [Study on the development of biological-active compounds after the model of natural products]. AB - In reviewing my lifework, I wish to summarize the results of studies on the development of new biological-active compounds. The following subjects are discussed: 1) syntheses and biological activities of benzoxazole derivatives, 2) structure-activity relationships of phyllodulcin, a natural sweetner, and 3,4 dihydroisocoumarins for sweetness, 3) syntheses and structure-activity relationships of spiro[isocoumarin-piperidine] analogs for antiallergic activity, 4) design, structure-activity relationships, and a mechanism of antitumor action of bistropolone derivatives, 5) design, structure-activity relationships of fused tetracyclic quinolines for antitumor activity. PMID- 1517980 TI - Action agenda for the 1990s. Reflections on directions for podiatric medical education. AB - The author reflects upon his experiences within podiatric medical education and shares his thoughts about the directions podiatric medical education should take before the end of the century. The author envisions a collaborative effort between the practitioners and educators within the profession in areas such as curriculum, research, academic health science centers, accreditation, and other important issues. The author calls for an education system relevant to and tested upon the anvil of patient care. PMID- 1517981 TI - CCPM and podiatric medical education. Preparing for the 21st century. AB - There are many changes on the horizon that will affect how we teach the future practitioners of podiatric medicine. The author describes the processes undertaken to date at the California College of Podiatric Medicine (CCPM), as well as the vision of tomorrow, for podiatric medical education. The educational system that will result from these changes will be more efficient; it will better meet the needs of students; and, it will broaden their base of knowledge, all to improve care given to the patient. PMID- 1517982 TI - Barry University School of Podiatric Medicine. The first seven years and beyond. PMID- 1517983 TI - Curriculum at the Scholl College. Toward mainstream medical education. AB - The Dr. William M. Scholl College of Podiatric Medicine in Chicago recently affiliated with a teaching hospital, the Illinois Masonic Medical Center, and used this alliance as a catalyst to effect a change in the clinical curriculum. The affiliation set up a joint venture to operate two clinics, one on Scholl College's traditional campus and one at the teaching hospital. At the hospital site, Scholl College students rotate through clinical externships in areas such as internal medicine, emergency medicine, and podiatric elective; podiatric and general medical residents assist in the tutelage of the students. At the Scholl College campus, beginning clinical students learn basic skills in a teaching clinic, then refine and further their skills in a comprehensive clinic under the guidance of faculty members. The faculty and administration at Scholl College have embraced the concept of mainstream medical education, and are striving to prepare podiatric physicians to practice 21st century medicine. PMID- 1517984 TI - College of Podiatric Medicine and Surgery in Des Moines. AB - The College of Podiatric Medicine and Surgery was established in 1981 as a fully integrated college of the University of Osteopathic Medicine and Health Sciences, Des Moines, Iowa, becoming the only school in the profession to be part of an academic health science center. Thus, this college provides a unique opportunity for the students and the podiatric medical profession to receive a multidisciplinary education, preparing them for podiatric medical practice as an integral part of total health care. PMID- 1517985 TI - Independent studies program in the basic sciences. A curricular innovation. AB - The Independent Studies Program was initiated at the New York College of Podiatric Medicine during the early months of 1987, and it has achieved continued success and acceptance from the administration, faculty, and students. The program emphasizes competence as the constant within a relatively time independent framework. This paper presents, in a longitudinal fashion, the Independent Studies Program as a program model that combines criterion referencing concepts, mastery-based learning combinations, and self-learning strategies. As a result, students have taken the initiative for diagnosing their learning needs, formulating their learning goals, identifying their human and material resources, and evaluating their learning outcomes. PMID- 1517986 TI - Challenges and opportunities facing the Ohio College of Podiatric Medicine. AB - This article presents the problems and challenges facing the Ohio College of Podiatric Medicine in the view of its President and its Chief Academic Officer. It explores the progress made and the challenges facing the Ohio College overall and in the areas of education. It presents an exciting new vision of the style of podiatric medical education, and the methods that are and will be used to assess the quality of the educational program. PMID- 1517987 TI - The future of podiatric medical education. Cautious optimism. AB - The leadership of the Pennsylvania College of Podiatric Medicine sets forth the following treatise on the outlook for podiatric medical education into the 21st century. Despite the seemingly impossible challenges facing the profession and its students, it is their opinion that the future is bright and with dedicated effort the profession will become stronger in the years ahead. PMID- 1517988 TI - Accreditation and the enhancement of the quality of professional education. AB - The postsecondary accreditation process is a unique system that attempts to evaluate and enhance the quality of higher and professional education in the United States. Critics of accreditation see the process as coercive and a deterrent to academic freedom while others call for accreditors to exercise greater authority. The origination of the process was a result of a number of coinciding events involving the development of educational and professional standards and concern over access. The current focus on assessment of educational outcomes has further established the credibility of postsecondary accreditation and its role in protecting the public interest. PMID- 1517989 TI - Health care perspectives. An interview with Congressman J. Roy Rowland. Interview by Richard B. Patterson. PMID- 1517990 TI - Relationship between fertilizing ability of frozen human spermatozoa and capacity for heparin binding and nuclear decondensation. AB - Nuclear decondensation of spermatozoa induced by heparin, reduced glutathione (GSH) or a mixture of heparin and GSH was studied using frozen-thawed human spermatozoa. The percentages of decondensed spermatozoa in controls and after treatment for 60 min with 30 mumol heparin l-1, 5 mmol GSH l-1, or heparin-GSH mixture were 1.5, 22.1, 4.3 and 37.6%, respectively. Most of the decondensed spermatozoa were eliminated by Percoll gradient centrifugation of samples previously treated with heparin or heparin-GSH mixture. However, comparable numbers of motile spermatozoa were recovered in the control and in each treated sample, demonstrating that a major proportion of motile spermatozoa was resistant to heparin (or heparin-GSH) effects on nuclear decondensation of spermatozoa. Fertilization of hamster oocytes was attempted using spermatozoa recovered in the 90% Percoll fraction and resistant to heparin-GSH decondensing mixture. Although insemination used a constant number of motile spermatozoa, fertilization rates were higher after treatments with heparin and GSH alone than in control or heparin-GSH-treated samples. In addition the number of spermatozoa that attached to the oocyte plasma membrane was a sixth or a half for sperm pretreated with heparin-GSH or heparin alone, respectively compared with untreated values. However, there was no evidence for induced acrosomal reaction by heparin and GSH, at least at the concentrations used. Qualitative analyses of heparin-binding sites were performed on untreated spermatozoa recovered in the 90% Percoll fraction by incubating spermatozoa in the presence of heparin covalently linked to albumin and coupled to colloidal gold (5 nm). Among this population of spermatozoa, 40.5% bound heparin-gold and labelling was mainly observed on the sperm head surface (88% of labelled spermatozoa) with (59.5%) or without (28.5%) tail labelling. Only a small proportion (23%) of spermatozoa that attached to the oocyte plasma membrane bound heparin-gold conjugate and only weak labelling was observed on the sperm head. Moreover, the proportion of spermatozoa that bound heparin-gold conjugate decreased (r = -0.77, P less than 0.0001) in relation to increasing concentrations of motile spermatozoa in the sample.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1517991 TI - Endogenous circannual rhythms and photorefractoriness of testis activity, moult and prolactin concentrations in mink (Mustela vison). AB - Mink are seasonal photosensitive breeders; testis activity is triggered when days have less than 10 h light. Increasing and decreasing plasma concentrations of prolactin induce the spring and autumn moults. In a 5 year experiment, males were maintained under short days (8 h light:16 h dark) at 13 degrees C or long days (16 h light:8 h dark) at 21 degrees C, winter and summer conditions, respectively. Under winter and summer conditions, circannual cycles of prolactin secretion and moulting were observed at intervals of about 11 months. Recurrence of testis cycles was not evident. In a second experiment, males were maintained under an 8 h light:16 h dark cycle from the winter solstice or under 10 h light:14 h dark, 12 h light:12 h dark or 14 h light:10 h dark cycles from 10 February. Under 8 h light:16 h dark cycle, testis regression was slightly later than under natural conditions, indicating photorefractoriness. However, mink remained sensitive to light: the longer the photoperiod, the faster the testis regression. In a third experiment, males were transferred under 8 h light:16 h dark or 16 h light:8 h dark from 15 May (group 1), 12 June (group 2) or 4 July (group 3); males submitted to long days received melatonin capsules on the day of transfer. Increasing concentrations of follicle-stimulating hormone (FSH) and luteinizing hormone (LH) and testis volume were shown by half the males in group 2 and nearly all the males in group 3; the constant release of melatonin from implants was more efficient than short days; but in the three groups, prolactin concentrations decreased in the few days after short-day or melatonin treatment. Overall, the results demonstrate endogenous circannual rhythms of prolactin secretion, body weight and moulting. Although a refractory period to short days was observed, the annual cycle of testis activity totally relies on the annual changes in daylength. PMID- 1517992 TI - Role of the embryonic vesicle and progesterone in embryonic loss in mares. AB - Characteristics of spontaneous embryonic loss in 21 mares were compared with those of 52 contemporary mares that maintained pregnancy. Embryonic losses were, in retrospect, grouped according to day of loss and length of the interovulatory interval, respectively, as follows: group 1, less than or equal to day 20 and less than or equal to 30 days (n = 10); group 2, less than or equal to day 20 and greater than 30 days (n = 3); and group 3, greater than day 20 and greater than 30 days (n = 8); ovulation was day 0. Mean diameter of the embryonic vesicle in group 1 was smaller (P less than 0.05) on days 12-18 than in the pregnancy maintained group, but among the pregnancy-maintained group and the embryonic-loss groups, the mean individual growth rates of vesicles was similar (no significant difference). A more frequent (P less than 0.05) location of the vesicles in the uterine body on day 13 in group 1 was due to a greater proportion of small vesicles and for day 18 was due to a greater incidence of fixation failure. Luteal regression occurred at the expected time in 77% of the mares with loss sooner than day 20. Low concentration of progesterone on days 12, 15 and 18, a detected decrease in diameter of the corpus luteum on days 15 and 18, and an interovulatory interval of less than or equal to 30 days indicated that luteolysis was not prevented by the embryonic vesicle in group 1.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1517993 TI - Factors influencing the rate of preantral and antral growth of mouse ovarian follicles in vitro. AB - The development of a culture system for individual mouse ovarian follicles using a low concentration of homologous serum, human follicle-stimulating hormone (hFSH) and a simple combination of growth factors is reported. Preantral follicles, 150 microns in diameter, with thecal cells attached were isolated mechanically. After 6-7 days on a Millicell membrane, a high proportion of the preantral follicles cultured individually with hFSH grew to morphologically normal large antral follicles (400-500 microns in diameter) with high oestradiol secretion. Without hFSH, the follicles grew to approximately 275 microns diameter in 6 days, but did not form antra or secrete oestradiol. The growth trajectory (overall pattern of growth formed by daily measurements of diameter) of each follicle was recorded and used as a measurement of response to experimental variation of culture conditions. The rapidly growing follicles were morphologically normal, but those that grew more slowly showed some abnormality or atresia and secreted less oestradiol. Follicles cultured in groups without being in direct contact with each other showed much poorer growth than those grown individually, but the inhibition was not uniform and some follicles grew larger than others in the group. Follicles that contacted each other directly in culture tended to fuse into one mass and their growth was substantially inhibited. Even under these conditions, one follicle often continued to grow slowly while the others degenerated. Such alteration of growth patterns suggests interfollicular paracrine control and may be a means of three-dimensional spacing of follicle growth within the ovary, as well as part of the mechanism of follicle selection. The dose-response curve based on the mean growth trajectory of follicles cultured individually, produced increasing rates of growth with 12.5 100 miu hFSH ml-1. Higher concentrations of hFSH did not increase growth rate further, but oestradiol secretion continued to increase with increasing hFSH up to the maximum used (2000 miu ml-1). PMID- 1517994 TI - Pregnancy rates and births after unilateral or bilateral transfer of bovine embryos produced in vitro. AB - Late morulae and blastocysts produced in vitro were nonsurgically transferred to heifers by unilateral (n = 184) or bilateral (n = 94) transfer. Of the recipients, 58% had serum progesterone values greater than 1.4 ng ml-1 on day 21 and rectal palpation on day 35 showed that 50% (138 of 278) were pregnant. The embryonic mortality rate between days 21 and 35 was estimated to be about 14% and between days 36 and 90 to be about 12%. Of the animals, 8% aborted between days 91 and 250 of pregnancy. No difference was observed in pregnancy rates between unilateral transfer of one (47%) or two embryos (49%) and bilateral transfer (53%), or in the twinning rate between bilateral transfer (42%) and unilateral transfer of two embryos (33%). The pregnancy rate was 54% with embryos evaluated as morphologically excellent or good, 51% with fair embryos and 26% with poor ones. A higher pregnancy rate (60%) was obtained after embryo transfer when the synchrony between recipient and embryo was -1 day. PMID- 1517995 TI - Follicular steroidogenesis and oocyte maturation after superovulation of goats (Capra hircus) with gonadotrophins. AB - Follicles were sampled at three different times after treatment with 1200 iu pregnant mares' serum gonadotrophin (PMSG) or 12 mg ovine follicle-stimulating hormone (FSH), and from untreated control animals. The meiotic status and protein synthesis of the oocyte from each follicle was determined and correlated with the intrafollicular concentration of oestradiol and progesterone. Significantly higher amounts of oestradiol were present in PMSG-treated animals at sponge withdrawal than in FSH-treated and control goats. Twenty hours later, both oestradiol and progesterone concentrations in the PMSG group were higher than those in the FSH group, and were equivalent to control animals at the onset of oestrus. At 18 h after the administration of human chorionic gonadotrophin (hCG), oestradiol decreased markedly in all three treatment groups, whereas progesterone remained significantly higher in PMSG-treated follicles. Although these high concentrations of intrafollicular steroids were associated with a higher incidence of premature condensation of chromatin in oocytes, the two events were not causally related. Moreover, cytoplasmic maturation was not prematurely activated in these oocytes and a changed pattern of protein synthesis was observed in oocytes from all three treatment groups after the hCG injection. Whereas disturbances in follicular steroidogenesis of oestradiol and progesterone occur in vivo in goats superovulated with PMSG, they do not underlie the premature activation of the initial stages of nuclear maturation in oocytes but are associated with normal cytoplasmic maturation. PMID- 1517996 TI - Polarized functions and permeability properties of rat epididymal epithelial cells in vitro. AB - Cultured rat caput and cauda epididymidal epithelial cells are shown to exhibit polarized properties characteristic of functioning epithelia. When grown on plastic substrates coated with reconstituted basement membrane, confluent monolayers of cells from both regions formed domes characteristic of other transporting epithelia. Immunocytochemical localization of three proteins characteristically associated with epithelial junctional complexes revealed that uvomorulin, zonula occludens 1 and cingulin were present in cultured epididymal epithelial cells and that their distribution was similar to that in the epididymal epithelium in vivo. These three molecules were not found in epididymal stromal cells. Cells from both regions growing in two compartment chambers developed an electrical resistance across the monolayer with a magnitude characteristic of high resistance epithelia. The optimal plating density of cells was 0.75 x 10(6) cells cm-2. The presence of reconstituted basement membrane on the filters did not affect the resistance of the cells. Inulin passage from basal to apical chambers was less than 2% over 24 h. These results show that several polarized functions of epididymal epithelial cells can be maintained in culture and that this type of culture system is useful for studying the function of the epididymis in vitro. PMID- 1517997 TI - Evidence for immunoreactive relaxin in boar seminal vesicles using combined light and electron microscope immunocytochemistry. AB - Light-microscope immunocytochemistry using the peroxidase-antiperoxidase technique and a polyclonal rabbit antiserum raised against purified porcine relaxin showed that cytoplasmic immunostaining for relaxin could be visualized in the epithelial cells of the seminal vesicle. No relaxin immunoreactivity was seen in the testis, epididymis, ductus deferens, prostate or bulbo-urethral gland. A ten times higher concentration of porcine relaxin antiserum was necessary to achieve immunostaining in the seminal vesicle comparable to that in the corpora lutea of pregnant sows. Ultrastructural examination showed that the epithelial cells of the boar seminal vesicle resembled typical protein-secreting cells with prominent rough endoplasmic reticulum and well-developed Golgi apparatus. The most striking feature of these cells was the accumulation of granules with a limiting membrane, which ranged from 200 to 600 nm in diameter and contained flocculent material of moderate electron density. Electron-microscope immunocytochemistry using the protein A-gold technique and relaxin antiserum demonstrated that the granules were the only intracellular organelles that showed immunoreactivity for relaxin. These results indicate that a relaxin-like substance is present in boar seminal vesicles and that the subcellular site of its localization is the granules, suggesting that the seminal vesicle produces and stores a relaxin-like substance, but that it is present at much lower concentrations than in the corpora lutea of pregnant sows. PMID- 1517998 TI - Development of rabbit preimplantation blastocysts cultured with precultured endometrial tissue. AB - Endometrial fragments were explanted from pseudopregnant rabbits 4.5 days after injecting with human chorionic gonadotrophin and were precultured for 2 days in suspension culture in the presence of oestradiol and progesterone equivalent to concentrations in rabbit serum at that stage. Preimplantation blastocysts were obtained at day 6.5 of pregnancy and cultured in the presence or absence of precultured endometrial fragments. Attachment of the trophoblast to the endometrium was prevented by continuous agitation. After 2 and 3 days, specimens were monitored for development in vitro using light and scanning electron microscopy. Although the development of blastocysts was slower in vitro than in vivo in both groups, development was clearly superior in the presence of precultured synchronous endometrial fragments. In the absence of endometrium, the embryonic anlage appeared disordered, particularly in the caudal region, but in the presence of uterine tissue the blastocysts developed much better. Up to nine somites were differentiated; the neural tube had started to close and the various parts of the brain anlage showed incipient differentiation. Syncytiotrophoblast differentiated in the presence or absence of endometrium in the embryonic and abembryonic hemispheres, but typical patterns were maintained better and cell degeneration was less frequent during co-culture. Although the culture model described here has not been optimized using criteria of blastocyst differentiation, the results suggest that culture of blastocysts with precultured synchronous endometrial fragments is advantageous. PMID- 1517999 TI - Role of androgens in survival of spermatozoa in epididymis of tammar wallaby (Macropus eugenii). AB - Studies of undiluted micropuncture samples of luminal fluid from the cauda epididymidis of the tammar indicated that spermatozoa are immotile in situ and spontaneously activate during collection or subsequent incubation in vitro. The suppression of sperm motility was related to the androgen status of the tammars and when this was increased by the use of Silastic implants of testosterone propionate, the spontaneous activation of samples was delayed for up to 2 h during incubation in vitro. Spermatozoa survived for up to 9 weeks when isolated in the cauda epididymidis between ligatures around the ductus. However, even after isolation for 3 weeks their viability was reduced compared with samples from the contralateral, unligated duct. Isolation of a length of ductus between ligatures also reduced the concentration of spermatozoa in the lumen of the duct and reduced the concentration of some proteins in the epididymal plasma. However, it did not affect the electrophoretic pattern of detergent extracts of spermatozoa. A study of the effects of orchidectomy and testosterone therapy indicated that sperm survival in the epididymis is androgen dependent. Orchidectomy reduced the concentration of spermatozoa in the luminal fluid and the volume of luminal fluid, and resulted in an increase in the concentration and a change in the electrophoretic pattern of protein in the fluid. The effects of orchidectomy were reduced or prevented by testosterone therapy. It is concluded that the cauda epididymidis of the tammar is at least as well adapted for sperm storage as it is in the eutherian mammals that have been studied. PMID- 1518000 TI - Changes in the properties and composition of zona pellucida of pigs during fertilization in vitro. AB - Several hundred fertilized pig eggs were prepared by an in vitro fertilization (IVF) technique in which follicular phase ovarian eggs were matured in vitro to metaphase II before incubation with capacitated epididymal spermatozoa for 12 h at 39 degrees C. Parthenogenetic eggs were also prepared by stimulation of the mature eggs with an electric pulse. The zonae were solubilized with 0.2% pronase/phosphate-buffered saline (PBS) or lactic acid/PBS. The time taken for solubilization was 30-40% shorter than for unfertilized eggs, indicating that zona hardening was induced during fertilization. At the same time, the sperm receptor activity of the zona was reduced. Electrophoretic analyses of zona glycoproteins from the ovarian, mature and fertilized eggs revealed that the amount of 90 kDa proteins decreased substantially during fertilization. This fraction could barely be detected in the zonae from parthenogenetic eggs. However, modification with a fluorescent probe showed that the general architecture of the zona remained unchanged during fertilization. These results suggest that the minor 90 kDa proteins are specifically degraded by the protease(s) released from the oocyte at fertilization, thereby leading to the block to polyspermy. PMID- 1518001 TI - Hormonal correlates of 'masculinization' in female spotted hyaenas (Crocuta crocuta). 1. Infancy to sexual maturity. AB - This report is concerned with hormone concentrations accompanying sexual maturation in a highly 'masculinized' female mammal, the spotted hyaena, Crocuta crocuta. Plasma concentrations of testosterone, androstenedione and oestrogen were determined by radioimmunoassay in a longitudinal study of 12 female and eight male hyaenas 2.5-62.5 months old. Concentrations of testosterone were significantly higher in males than in females after 26.5 months of age, but earlier measurements did not differ between sexes. Mean testosterone concentrations in adult female hyaenas (0.4-0.5 ng ml-1) were similar to those in several other female mammals that do not display a 'masculine' profile, but mean concentrations of androstenedione (2.5-5.5 ng ml-1) in female hyaenas were significantly higher than in males (1.0-2.0 ng ml-1), at most ages. Oestrogen could not be detected (less than 0.03 ng ml-1) in females until about 14 months of age and then increased (to approximately 0.13 ng ml-1) between 18 and 30 months; oestrogen remained undetectable in males. This rise in oestrogen in females corresponded to nipple enlargement and to changes in the size and elasticity of the urogenital meatus, permitting copulation and parturition through the clitoris. Gonadectomy (two males and four females) at 4-7 months resulted in nondetectable concentrations of testosterone and oestrogen and a marked attenuation in androstenedione (to approximately 0.39 ng ml-1), indicating that the gonads are the major source of these three steroids. Gonadectomy also eliminated sex differences in weight, nipple development and elasticity of the urogenital meatus. PMID- 1518002 TI - Hormonal correlates of 'masculinization' in female spotted hyaenas (Crocuta crocuta). 2. Maternal and fetal steroids. AB - Concentrations of androgens (androstenedione, testosterone, 5 alpha dihydrotestosterone), oestrogen and progesterone were measured in relation to pregnancy in the spotted hyaena (Crocuta crocuta). The gestation period was estimated to be about 110 days. There was a marked progressive rise in all the steroids starting in the first third of gestation. Chromatographic separation of plasma showed that much of the oestrogen is not oestradiol (only 12% of total measured) and that a significant fraction of the 'testosterone' may be dihydrotestosterone. In the final third of pregnancy, concentrations of androgen (especially testosterone plus dihydrotestosterone) in the female circulation reached the maximal values of adult males; the percentage of dihydrotestosterone relative to total testosterone plus dihydrotestosterone was higher in females (44 +/- 3.9%, n = 20) than in males (29.5 +/- 3.5%, n = 17). Plasma androstenedione was also significantly higher in females, but the increment was less than for oestrogen, testosterone and progesterone, and the temporal pattern was less clear. Samples from the maternal uterine and ovarian circulation showed that androstenedione is largely of ovarian origin and metabolized by the placenta, while testosterone, progesterone and oestrogen are primarily of placental or uterine origin. Fetal samples were taken from two mixed-sex sets of twins and one male singleton. Gradients across the placenta measured in the fetal circulation confirmed that the placenta metabolizes androstenedione and is a source of testosterone for the female fetus; there were no consistent differences in androgens between male and female fetuses. It is suggested that the conspicuous masculinization of the female spotted hyaena, especially evident in the external genitalia at birth, is a result, at least in part, of high placental production of testosterone or dihydrotestosterone derived from the metabolism of high maternal androstenedione. PMID- 1518003 TI - Effects of pig follicular fluid on maturation of pig oocytes in vitro and on their subsequent fertilizing and developmental capacity in vitro. AB - This study examines the effects of pig follicular fluid on the maturation of pig oocytes and on their subsequent fertilizing and developmental capacity in vitro. The addition of pig follicular fluid or its fractions obtained by ultrafiltration, gel filtration and ion-exchange chromatography to maturation medium significantly increased the rates of nuclear maturation, normal fertilization and normal cleavage of pig oocytes after fertilization in vitro: the rates of normal fertilization and cleavage were 2-4 times higher than those in the control medium. The efficacy of pig follicular fluid was lost after heating at 56 degrees C for 30 min, whereas no significant decrease in activity was observed after defatting. In addition, the effective component(s) was partially purified by ultrafiltration, gel filtration and ion-exchange chromatography: the activity was observed in the fraction (UF2; M(r) 10,000 20,000) obtained by ultrafiltration. Activity was found in the first fraction (G1) obtained by gel filtration of UF2. Among three fractions obtained by ion exchange chromatography of G1, only the third fraction had the activity. The results indicate that pig follicular fluid contains an acidic substance(s) (M(r) 10,000-200,000) that promotes oocyte maturation. PMID- 1518004 TI - Concentrations of immunoreactive inhibin in ovarian and peripheral venous plasma and follicular fluid of Booroola ewes that are homozygous carriers or non carriers of the FecB gene. AB - No gene-specific differences were found during either the luteal or follicular phases of the oestrous cycle in the venous secretion rates of ovaries or in concentrations of immunoreactive inhibin in peripheral plasma between Booroola ewes that were homozygous carriers (BB) or non-carriers (++) of the FecB gene. In three experiments in which concentrations of plasma inhibin and follicle stimulating hormone (FSH) were compared, gene-specific differences were noted for FSH (P less than 0.05), but no significant correlations were noted between FSH and inhibin for either genotype. Granulosa cells and follicular fluid, but not theca interna, stroma or corpora lutea, were the major intra-ovarian sites of inhibin; no gene-specific differences were noted for inhibin concentrations in follicular fluid or in any of the intra-ovarian tissues. The mean concentrations of inhibin in follicular fluid remained constant irrespective of follicular diameter whereas the mean total contents of inhibin increased significantly with increasing diameter (P less than 0.05). Inhibin secretion rates were four times higher in ovaries with oestrogen-enriched follicles (i.e. greater than or equal to 50 ng oestradiol ml-1) than in ovaries with no such follicles (P less than 0.01). Moreover, inhibin concentrations were higher in follicular fluid of oestrogen-enriched follicles than in those with low oestrogen (i.e. less than 50 ng ml-1; P less than 0.05). Ovariectomy resulted in a significant reduction in concentrations of immunoreactive inhibin from plasma (P less than 0.01). The residual plasma inhibin in some Booroola ewes was not associated with genotype. It is concluded that, although antral follicles are a major source of inhibin in Booroola ewes, immunoreactive inhibin is not associated with the FecB gene and is not responsible for the gene-specific differences in concentrations of FSH in plasma. PMID- 1518005 TI - The dynamic provision of different energy substrates improves development of one cell random-bred mouse embryos in vitro. AB - Preliminary observations showed that one-cell embryos from random-bred MF1 mice avoid cleavage arrest at the two-cell stage ('in vitro two-cell block') when cultured in modified M16 culture medium containing lactate and pyruvate but lacking glucose. The roles of lactate, pyruvate and glucose during preimplantation development of embryos from random-bred mice in vitro were therefore examined. When all three substrates were present continuously during culture, one-cell embryos arrested at the two- to four-cell stages. Improved development to the morula stage after 96 h in culture was obtained in media containing pyruvate alone, lactate and pyruvate, pyruvate and glucose, lactate pyruvate and glucose for the first 24 h, and medium containing lactate and pyruvate for the remaining 72 h. In a second experiment, embryos were cultured in medium containing pyruvate alone, lactate and pyruvate or pyruvate and glucose for the first 24 h, and lactate plus pyruvate medium for the second 24 h. Subsequent transfer to medium containing lactate, pyruvate and glucose supported the morula to blastocyst transition. These results show that developmental arrest in vitro can be overcome by changing the combination of energy substrates at different stages of preimplantation development. PMID- 1518006 TI - Histology of ovaries of female rabbits immunized with deglycosylated zona pellucida macromolecules of pigs. AB - Female rabbits (n = 36, 6 per group) were immunized with: (i) solubilized isolated porcine zona pellucida (SIZP), which contains ZP1, 82 kDa; ZP3 alpha, 55 kDa; and ZP3 beta, 55 kDa; (ii) a purified preparation of ZP3 alpha and ZP3 beta (ZP3); (iii) purified endo-beta-galactosidase digested glycoproteins ZP3 alpha (EBGD) and (iv) ZP3 beta-(EBGD) (each about 30% deglycosylated); (v) chemically deglycosylated core proteins ZP3 alpha-(DG) and (vi) ZP3 beta-DG (each greater than 92% deglycosylated). Rabbits injected with saline (n = 6) or Freund's adjuvant (n = 6) served as controls. Rabbits were bled weekly to monitor titres. Every six weeks two animals from each group (n = 16) were selected for unilateral oophorectomy followed by histological examination. Sections were scored for numbers of primary, secondary and tertiary follicles. Anti-ZP3 titres developed in all treatment groups and correlated with carbohydrate content (peak per cent [125I]-labelled ZP3 binding by radioimmunoassay: SIZP 71.9 +/- 1.2, ZP3 70.0 +/- 2.5, ZP3 alpha-EBGD 60.9 +/- 5.3, ZP3 beta-EBGD 56.4 +/- 5.0, ZP3 alpha-DG 56.4 +/- 4.0, ZP3 beta-DG 53.5 +/- 4.3) (means +/- SEM). Animals immunized with SIZP, ZP3 and ZP3 beta-EBGD showed a statistically significant reduction in the number of primary, secondary and tertiary follicles compared with controls (P less than 0.01, MANOVA), whereas animals immunized with ZP3 alpha-EBGD, ZP3 alpha-DG and ZP3 beta-DG did not (P greater than 0.05, MANOVA). These results demonstrate that immunization with purified ZP3 alpha macromolecules (ZP3 alpha-EBGD, ZP3 alpha DG) or ZP3 beta-DG does not produce histopathological changes in ovaries. Such deglycosylated ZP macromolecules represent potential target antigens for immunocontraceptive development. PMID- 1518007 TI - Embryo-initiated oviductal transport in mares. AB - The hypothesis that equine embryos initiate oviductal transport in mares was tested by placing day 6 uterine embryos in the oviducts of day 2 (n = 10) or day 5 (n = 10) recipient mares and attempting to collect the embryos from the uterus 48 h later. To determine whether the surgical transfer procedure initiated oviductal transport, medium alone was placed in the oviducts of day 2 (n = 10) inseminated mares (sham transfer), and uterine embryo collections were attempted 48 h later. Embryos were transported through the oviduct of day 2 recipients by day 4 (instead of day 5 to 6) in six of ten mares, which was not significantly less (P greater than 0.1) than in day 5 recipients (9 of 10). Oviductal transport was not primarily initiated by the surgical transfer procedure, since oviductal transport occurred in only one sham transfer. There was no significant difference (P greater than 0.1) in the diameter of embryos placed in the oviducts of day 2 and day 5 recipient mares (180 +/- 13.8 versus 187 +/- 11.3 microns, respectively). However, embryos collected from the uterus were significantly smaller (P less than 0.05) in day 2 than in day 5 recipients (375 +/- 85.4 versus 659 +/- 43.6 microns, respectively). One uterine embryo had shed its zona pellucida before being placed in, and transported through, the oviduct of the recipient mare. PMID- 1518008 TI - Localized increases in ovarian vascular permeability and leucocyte accumulation after induced ovulation in rabbits. AB - Colloidal carbon was injected i.v. in mature virgin rabbits at different times after induction of ovulation by human chorionic gonadotrophin (hCG, 100 iu) or mating. Before induction of ovulation, slight carbon leakage was observed in the inner vascular ring of the theca interna of antral follicles, but blood vessels in the other ovarian compartments were unstained. Between 4 and 10.5 h after hCG treatment or mating, vascular leakage was most marked in the blood vessels of the interstitial gland and in the theca interna of antral follicles. Just before ovulation, carbon particles were observed between granulosa cells and some carbon was seeping into the follicular fluid of preruptured follicles. Vascular leakage was also observed over the follicle dome before rupture as well as at the dorsomedial junction between the mesovarium and the ovary. The blood vessels stained with carbon were 7-70 microns diameter, representing capillaries and postcapillary venules. About 6 h after hCG injection, an increased number of polymorphonuclear leucocytes migrated from the vessels of these ovarian compartments into the surrounding interstitial tissue. The number of leucocytes seen in the follicular wall and ovarian medulla increased markedly towards ovulation. During early corpus luteum formation, the number of leucocytes decreased markedly. The localized vascular changes seen after mating and hCG stimulation were similar to an inflammatory reaction and could form the basis for the formation of peritoneal exudate after ovulation in rabbits and periovulatory ascitic accumulation seen in the peritoneal cavity of women during the menstrual cycle. PMID- 1518009 TI - Increase in uterine peroxidase activity in the rat uterus during oestrogen hyperaemia. AB - The administration of oestrogen results in increased arterial blood flow in all mammalian species studied to date, but its mechanism of action has not been elucidated. Because an interval of 30-60 min is observed between oestrogen injection and uterine hyperaemia, it has been suggested that a vasoactive intermediate is involved and recent evidence suggests that catechol oestrogens are the vasoactive oestrogen intermediates. Uterine peroxidase catalyses the conversion of oestrogens to their catechol forms and thus may play an important role in oestrogen-induced uterine hyperaemia. The present studies evaluated the time course and dose-response effects of oestrogen on uterine peroxidase activity and related these to changes in uterine blood volume, an index of uterine hyperaemia in immature rats. These data demonstrated that the minimal effective hyperaemic dose of oestradiol also increased (P less than 0.05) uterine peroxidase activity. The oestradiol-induced increase in uterine peroxidase activity preceded significant increases in uterine blood volume (1 h versus 2 h, respectively). These data are consistent with a role for peroxidase-mediated conversion of oestradiol to catechol oestradiol in facilitating uterine hyperaemia in rats. PMID- 1518010 TI - Localization of type I interferon in murine trophoblast and decidua during decidual formation. AB - Mouse trophoblast and decidua were examined by means of immunohistochemistry to define the localization of type I interferon. The decidua were stained for type I interferon at the time of implantation. The strong reaction was first observed in the primary decidual zone on day 5 and subsequently in the secondary decidual zone on day 6. After day 10, the decidua basalis and decidua capsularis showed a strong reaction. At the one-cell stage, embryos were weakly labelled, but a positive reaction was recognized in compacted morulae. Blastocysts on days 3 and 4 were positive in trophoblast and inner cell mass and a strong reaction was observed in the primitive endoderm on day 4. The visceral endoderm on day 5 and the trophoblast on day 6 were positive. After day 10, the trophoblast giant cells, labyrinth, visceral yolk sac and fetal blood cells gave a positive reaction. This study is the first demonstration of type I interferon localization in situ in mouse trophoblast and decidua during decidual formation. PMID- 1518011 TI - Influence of a gonadotrophin-releasing hormone agonist and gonadotrophins on morphometric characteristics of the population of small ovarian follicles in cynomolgus monkeys (Macaca fascicularis). AB - Small follicles, less than or equal to 100 microns, in monkey ovaries were divided into four types based on the morphological characteristics of the granulosa cells that surrounded the oocyte: primordial, intermediary, primary and secondary follicles. The proportion of primordial follicles positively correlated, whereas those of intermediary, primary and secondary follicles negatively correlated, with the total number of follicles less than or equal to 100 microns. There was no relationship between the population of nongrowing follicles (primordial and intermediary) and that of early-growing follicles (primary and secondary). Administration of exogenous gonadotrophins did not induce significant changes in the population of small follicles, whereas there was a significant increase in the number of intermediary follicles when gonadotrophins were associated with a gonadotrophin-releasing hormone agonist, buserelin. Buserelin can therefore partly inhibit the initiation of ovarian follicular growth in monkeys. PMID- 1518012 TI - Effect of human chorionic gonadotrophin on dominant follicles in cows: formation of accessory corpora lutea, progesterone production and pregnancy rates. AB - Thirty-four lactating Holstein cows were randomly assigned to four groups for treatment with human chorionic gonadotrophin (hCG, 1000 iu) at insemination day 0 (n = 8) or 7 (n = 9) or 14 days (n = 9) after insemination or with no hCG treatment (control, n = 8). Ultrasound imaging of the ovaries and plasma progesterone measurements were carried out to determine follicular dynamics and corpus luteum growth and function. Rates of formation of accessory corpora lutea were higher among cows treated on days 0 (three cows), 7 (seven cows) or 14 (four cows) than in the controls (one cow). Total corpus luteum diameter was greater (P less than 0.01) among hCG-treated cows than in controls 7-42 days after insemination. Concentrations of progesterone in plasma were significantly (P less than 0.05) higher in cows treated with hCG on days 7 or 14 than in those treated on day 0 or in controls, at days 18, 35 or 42 after insemination. Seven of the cows treated on day 7 became pregnant, whereas four, four and three cows treated on days 0 or 14 and control cows became pregnant, respectively. The results suggest that hCG treatment at 7 days after insemination could be used to produce accessory corpora lutea, raise plasma progesterone concentration and hence reduce the incidence of early embryonic mortality in cattle. PMID- 1518013 TI - Developmentally related changes in the metabolism of glucose and glutamine by cattle embryos produced and co-cultured in vitro. AB - The metabolism of radiolabelled glucose and glutamine was measured in individual cattle embryos produced by in vitro maturation and fertilization of oocytes, and culture with bovine oviductal epithelial cells. Metabolism of glucose through the pentose-phosphate pathway increased almost 15 times and the total metabolism of glucose 30 times, during development from the two-cell to the expanded blastocyst stage. The first marked increase in glucose metabolism did not occur until between the eight- and 16-cell stages, the time of activation of the embryonic genome. Conversely, the metabolism of glutamine was high in two- and four-cell embryos and then decreased to reach a minimum at the compacted morula to blastocyst stage, possibly because of degradation of maternally derived enzymes. Blastocyst expansion was accompanied by significant increases in the metabolism of glucose and glutamine, presumably reflecting the increased energy demands of Na(+)-K+ ATPase necessary for formation and maintenance of the blastocoel. PMID- 1518014 TI - In vitro maturation, fertilization and development of follicular oocytes from buffalo (Bubalus bubalis). AB - Cumulus-oocyte complexes, 5596, were cultured for 24 h in either TCM-199 or Ham's F-10 with or without gonadotrophins and supplemented with either 20% buffalo oestrous serum (BES) or fetal calf serum (FCS). The maturation rates of oocytes cultured in TCM-199 or Ham's F-10 medium supplemented with 20% BES were 47.4 +/- 17.8 and 44.8 +/- 25.6, respectively. Addition of luteinizing hormone (LH) (5 micrograms ml-1) significantly improved the maturation rate in the Ham's F-10 medium supplemented with 20% BES (76.8 +/- 18.3), but follicle-stimulating hormone (FSH) (0.5 micrograms ml-1) and oestradiol (1 microgram ml-1) failed to synergize with LH (71.7 +/- 19.5). In the TCM-199 system, LH failed to enhance the maturation rate but the addition of FSH and oestradiol significantly enhanced the proportion of mature oocytes (42.7 +/- 1.4 and 81.7 +/- 14.5, respectively; P less than 0.05). Frozen-thawed spermatozoa prepared in Bracket and Oliphant (BO) medium and treated with 5 mmol caffeine 1(-1) + 10 micrograms heparin showed a higher fertilization rate (29.8%) than those treated in Hepes-Talp and treated with 10 micrograms heparin ml-1 (19.6%). Fertilization rate was significantly improved when fresh ejaculated spermatozoa treated with 5 mmol caffeine 1-1 and 10 micrograms heparin in BO medium (50%) was used. Rate of cleavage and development were also higher when in vitro fertilization was carried out with fresh ejaculated spermatozoa treated with caffeine and heparin (34.1 and 36.8%, respectively) than with frozen-thawed spermatozoa (27.0 and 22.0%, respectively). Development rate was enhanced when fertilized ova were cultured in ligated rabbit oviduct (28.0%) than when co-cultured on oviductal cell monolayers (8.2%). The results indicate that oocytes cultured in medium supplemented with BES and gonadotrophins reveal high rates of maturation and development to the blastocyst stage after fertilization with fresh ejaculated spermatozoa. PMID- 1518015 TI - Interbirth interval and duration of pregnancy in hares. AB - The possibility of inducing superfetation in hares by artificial insemination (AI) was investigated. AI performed on various days during the second half of gestation did not result in new pregnancies, but all ongoing pregnancies were terminated 1-4 days after AI. We suggest that copulation during the last week of pregnancy, common among captive hares, may have a similar effect to that of AI in terminating pregnancies and inducing early deliveries. Intervals between successive deliveries that are shorter than the normal duration of gestation do not necessarily indicate superfetation and this phenomenon may be rare among hares in captivity as well as in the wild. PMID- 1518016 TI - Effects of removal of chicks from hens on concentrations of prolactin, luteinizing hormone and oestradiol in plasma of brooding Gifujidori hens. AB - Gifujidori hens were allowed to repeat a breeding cycle in one season. In the first breeding cycle the duration of the brooding (raising chicks) stage was limited to 3 weeks, whereas in the second breeding cycle it was limited to 1 week by removing all chicks from mother hens. In the first breeding cycle, plasma prolactin (PRL) was high during the incubation period, but rapidly decreased on the day of hatching and reached minimum values about 1 week after hatching. In contrast, plasma luteinizing hormone (LH) concentrations were low during the incubation period, but after hatching they gradually increased and reached peak values immediately after removal of chicks. Concentrations of oestradiol in plasma were low in the incubation and brooding stages but increased significantly immediately after removal of chicks. In the second breeding cycle, changes in PRL and LH concentrations were similar to those observed in the first breeding cycle except that even greater increases in plasma LH and oestradiol concentrations were observed one week after hatching when the chicks were removed. These results suggest that coexistence of newly hatched chicks may suppress LH secretion from the pituitary of the hen in the natural breeding cycle. PMID- 1518017 TI - Endothelin-like immunoreactivity in human endometrium. AB - Endothelin-like immunoreactivity (ET-IR) was detected immunocytochemically in glandular epithelium and vascular endothelium of human endometrium and myometrium. Primary antibody was raised in rabbits against the carboxy-terminal heptapeptide of endothelin 1 (ET-1), ET-1(15-21), and compared with antibodies raised against the cyclized amino-terminal, ET-1(2-13), and commercially obtained antibodies against the whole ET-1 or ET-3 molecule. Binding was visualized using the peroxidase technique in sections counter-stained with haemalum. Staining was seen in each of 15 sections from eight women in the proliferative (five) or secretory (three) phase of the cycle. Intense staining was present in the cytoplasm of endometrial glands and vascular endothelium, and was greatest at the endometrial-myometrial junction. The pattern of staining was similar with all primary antibodies tested. The demonstration of ET-IR in endometrium suggests that the endothelins may play a role in control of the uterine vascular bed. PMID- 1518018 TI - Retardation of pubertal development by prenatal long days in goat kids born in autumn. AB - Goat kids born in spring attain sexual maturity during the first autumn after birth in temperate regions, at about 30 weeks of age. This study observed sexual development in autumn-born kids and the influence of late-summer, prenatal light treatment on onset of puberty. The breeding season of 14 female British Saanen dairy goats was artificially advanced by 4 months, using a treatment of long days during the winter followed by melatonin treatment in spring. Five goats were treated with a photoperiod of 20 h light:4 h dark (lights on 04.00 h) for 62.1 +/ 1.4 days (mean +/- SEM, n = 5) prepartum (14 August to 15 October). The remaining nine goats were kept under a natural photoperiod: 20 kids from these mothers were followed, five males and five females from each group. Testicular development was assessed by means of weekly measurement of scrotal circumference. Blood samples were taken once a week from all kids from 4 weeks of age for 5 months. Plasma was assayed for progesterone in females and testosterone in males. Autumn-born female kids initiated oestrous cyclicity in January, at a mean age of 12.8 +/- 0.8 weeks. Puberty onset was significantly delayed (P less than 0.03, unpaired Student's t test) in females exposed to 20 h light:4 h dark in utero and occurred at a mean age of 16.5 +/- 1.4 weeks. Testicular development was significantly delayed and plasma testosterone concentrations were lower in autumn born male kids that experienced 20 h light:4 h dark in utero than in kids from mothers in a natural photoperiod.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1518019 TI - Genetic deafness. PMID- 1518020 TI - Hereditary haemorrhagic telangiectasia: a clinical analysis. AB - Data from 98 patients with hereditary haemorrhagic telangiectasia (HHT) are presented. All were symptomatic by 40 years of age and 62% by 16 years. Nose bleeding was the first symptom of disease in 90% of cases with mucocutaneous telangiectases appearing 5 to 20 years later. Complications of HHT are discussed and an age of onset curve given. PMID- 1518021 TI - Genetic transmission of colorectal cancer: exploratory data analysis from a population based registry. AB - Classical segregation analysis was conducted on 605 families of probands with colorectal carcinoma ascertained through the Cancer Registry of the Province of Modena in Italy. The families were classified as 28 suspected hereditary non polyposis colorectal cancer (HNPCC) syndromes and 577 presumed non-HNPCC. In 11 of these, both parents had colorectal carcinoma, in 130 one parent was affected, and in 436 both parents were normal. In the suspected HNPCC families, segregation was compatible with dominant transmission of susceptibility to carcinoma. In families with one parent affected, the segregation frequency was almost exactly equal to the frequency of segregation in families where both parents were normal. The model of dominant transmission of susceptibility through a major gene with greatly reduced penetrance in heterozygotes fitted the data acceptably. PMID- 1518022 TI - Comparison of adult height between patients with XX and XY gonadal dysgenesis: support for a Y specific growth gene(s). AB - Adult height was compared between published cases of patients with XX gonadal dysgenesis (XXGD) and those with XY gonadal dysgenesis (XYGD). The mean adult height of XYGD patients (171.0 cm (SD 7.8), n = 27) was significantly greater than that of XXGD patients (164.4 cm (7.7), n = 27) (p less than 0.01). This finding supports the existence of a Y specific growth gene(s) which promotes statural growth independently of the effects of gonadal sex steroids. PMID- 1518023 TI - Minute Y chromosome derived marker in a child with gonadoblastoma: cytogenetic and DNA studies. AB - A 12 year old girl referred for chromosome analysis because of short stature was found to have karyotype mos 45,X/46,X,+mar. The marker chromosome was observed in 58% of her blood lymphocytes. It was a small, pale staining, spherical fragment with GTL banding and showed faint differentiation along its length with CBG banding. DNA analysis using Y specific probes showed the absence of the testicular determining region and the presence of some short arm and centromeric Y chromosomal material. In situ hybridisation confirmed that the Y chromosomal material was associated with the marker chromosome. At laparotomy the patient was found to have streak gonads. Gonadectomy was subsequently performed and histological examination showed dysgenetic gonads with a dysgerminoma arising from a gonadoblastoma in the left gonad. This case shows that even very small Y derived marker chromosomes with pericentric material can predispose the phenotypic female to gonadal neoplasia. PMID- 1518024 TI - Racial distribution of Duchenne muscular dystrophy in the West Midlands region of Britain. AB - In the West Midlands region of Britain, Duchenne muscular dystrophy (DMD) is twice as common as expected in Indians, and is less common than expected in Pakistanis. Although the numbers are small, they cannot be explained by any bias of ascertainment and are considered to be real. One possible mechanism for the high frequency of DMD in Indians is the presence of repetitive elements in the wild type gene which predispose to mutations. PMID- 1518025 TI - Investigation of a female manifesting Becker muscular dystrophy. AB - Females manifesting Becker muscular dystrophy (BMD) are even more rarely observed than for the allelic condition Duchenne muscular dystrophy. The male proband has typical BMD with greatly raised CK activity and a myopathic muscle biopsy. His mother experienced walking difficulties from 35 years of age and has a myopathy with marked calf hypertrophy, a raised CK, and a myopathic muscle biopsy. Dystrophin analysis was undertaken on both the proband and his mother. Immunoblotting showed a protein of normal size but of reduced abundance in both. Immunocytochemical analysis in the proband indicated that the majority of the fibres showed weak dystrophin labelling and in his mother both dystrophin positive and dystrophin negative fibres were present. Non-random X inactivation at locus DXS255, was observed in DNA isolated from peripheral lymphocytes of the mother. Neither extended multiplex PCR performed on DNA from the proband nor analysis of lymphocyte derived mRNA showed a structural alteration in the dystrophin gene suggesting that an unusual mutation was responsible for BMD in this family. PMID- 1518026 TI - Congenital hydrocephalus secondary to Walker-Warburg syndrome identified on the Manitoba Neonatal Screening Programme for Duchenne muscular dystrophy. AB - This report describes our first experience with a clinically important true false positive neonatal screening test for Duchenne muscular dystrophy (DMD). Neonatal screening for DMD began as a pilot programme in Manitoba on 1 January 1986 by analysis of creatine kinase (CK) activity in dried filter paper blood spots. To date, all except two males with positive initial and follow up neonatal CK screening tests were subsequently diagnosed as having DMD. Of these two, one was a newborn male with congenital hydrocephalus whose positive DMD screening test led to the identification of an associated congenital myopathy and confirmation of the diagnosis of Walker-Warburg syndrome. PMID- 1518027 TI - Simultaneous partial monosomy 10p and trisomy 5q in a case of hypoparathyroidism. AB - We report a case of monosomy for the distal region of the short arm of chromosome 10 (p13----ter) associated with trisomy for the terminal region of the long arm of chromosome 5 (q35.2----ter) that had originated from adjacent 1 segregation of a maternal reciprocal balanced translocation (5;10)(q35.2;p13). We review the clinical findings of previously reported cases of both partial monosomy for 10p and of partial trisomy for 5q, but to our knowledge there are no previous reports of the effects of these two chromosome anomalies together. Clinically our patient showed features typical of partial monosomy for 10p (including hypothyroidism) rather than partial trisomy 5q. PMID- 1518028 TI - Upper limb defect associated with developmental delay, unilateral poorly developed antihelix, hearing deficit, and bilateral choroid coloboma: a new syndrome. AB - Two sibs are reported with upper limb defect, developmental delay, central hearing loss, unilateral poorly developed antihelix, and bilateral choroid coloboma. The inheritance is probably autosomal recessive. PMID- 1518029 TI - Progressive vitiligo, mental retardation, facial dysmorphism, and urethral duplication without chromosomal breakage or immunodeficiency. AB - A boy, born to first cousin parents of Algerian origin, first presented at the age of 9 years with growth failure, mental retardation, and dysmorphic facies. Progressive vitiligo developed from the age of 12 and distal duplication of the urethra was later recognised. The basis of this syndrome remains to be determined; autoimmune disease, chromosomal breakage syndromes, and other neurocutaneous syndromes have been excluded. PMID- 1518030 TI - Mild pulmonary disease in a cystic fibrosis child homozygous for R553X. PMID- 1518031 TI - High proportion of twins in carriers of fragile X syndrome. PMID- 1518032 TI - Spotted fever in the Mediterranean. PMID- 1518033 TI - Comparison of a blood-free medium and a filtration technique for the isolation of Campylobacter spp. from diarrhoeal stools of hospitalised patients in central Australia. AB - Single specimens of diarrhoeal stool from 676 patients, mostly aboriginals aged less than 5 years, admitted to Alice Springs Hospital, central Australia, for diarrhoea between Sept. 1988 and Feb. 1989, were examined for Campylobacter spp. by culture on a blood-free medium with selective supplement (BFM; Oxoid) and blood agar overlaid with a membrane filter (FM). Campylobacter spp. were isolated on either BFM or FM or both from 225 patients. Campylobacter spp. were isolated on BFM alone from 75 patients and on FM alone from 213 patients (p less than 0.001; chi 2 test). Most campylobacters isolated on BFM were C. jejuni. All C. jejuni subsp. doylei, all "C. upsaliensis" except one, all C. laridis, C. fetus subsp. fetus and several uncharacterised Campylobacter isolates were isolated on FM only. C. jejuni was isolated on BFM but not FM from several patients, and vice versa. Serotyping of C. jejuni and C. coli isolated from both media showed the serotypes recovered from the two media to be different in some patients. In some patients concurrent infection with several species or serotypes (up to five) of Campylobacter, or both, was shown for the first time by the use of FM. We conclude that the use in combination of a selective medium and a non-selective medium with a filtration technique are better than either medium alone for the isolation of Campylobacter spp. PMID- 1518034 TI - Carotenoid pigment levels in Staphylococcus aureus and sensitivity to oleic acid. AB - Staphylococcus aureus mutants lacking pigment, or expressing only low levels of pigment, were more sensitive to oleic acid than were the parent strain and mutants making more pigment than the parent. One class of mutants (colour index 5), although possessing significant levels of pigment, were nevertheless quite sensitive to oleic acid. This suggested that only certain carotenoids in the biosynthetic pathway were capable of imparting resistance to fatty acids. The phenotypic expression of pigment also affected the sensitivity of a strain to oleic acid. The parent S. aureus strain 18Z, when grown to express its maximal pigment potential, was more resistant to oleic acid than when it was grown to express minimal levels of pigment. PMID- 1518035 TI - The typing of Staphylococcus epidermidis by a lectin-binding assay. AB - A new typing method for Staphylococcus epidermidis was developed. Four biotinylated lectins--wheat germ agglutinin (WGA), soy bean agglutinin (SBA), lentil agglutinin (LCA) and Concanavalin A (ConA)--were added to immobilised whole cells of coagulase-negative staphylococci (CNS) in microtitration plates. The amount of bound lectin was measured by peroxidase-conjugated avidin followed by a peroxidase reaction. The method was compared to antibiotic-resistance analysis, phage typing, plasmid DNA profiles and slime production. A total of 113 isolates of CNS from 21 patients was investigated and 71 strains of CNS, including 64 strains of S. epidermidis, were detected if all typing methods were taken into consideration. If only one typing method was used the highest discriminatory power among the S. epidermidis isolates was obtained with the lectin-binding assay which allowed 49 different strains to be detected. If the lectin-binding assay was combined with plasmid-profile analysis, all 64 different strains could be identified. The typability of lectin-binding assay was 96.9% among the S. epidermidis isolates and 25 different lectin-binding patterns were established among the 64 strains. The highest number of strains belonging to one lectin-binding pattern was 13 (20.3%). The assay was reproducible, easy to perform, relatively inexpensive and therefore applicable to large scale typing of S. epidermidis. PMID- 1518036 TI - Purification and characterisation of elastase from Staphylococcus epidermidis. AB - An elastase of Staphylococcus epidermidis was purified by ion exchange chromatography on CM-Sepharose and characterised. Its M(r) is c. 21 kDa, its optimal temperature for activity is 42 degrees C and the pH optimum is 6.8. The enzyme is activated by cysteine and other SH-donators and inhibited by L-trans epoxy-succinylleucylamido-(4-guanidino)butane (E64), an inhibitor of cysteine proteases, but not by 3,4-dichloroisocoumarin (3,4-DCI), an inhibitor of serine proteases. This finding suggests that the elastase of S. epidermidis is a cysteine protease. Because S. epidermidis elastase degrades human sIgA, IgM, serum albumin, fibrinogen, and fibronectin, this enzyme may be regarded as a virulence factor. PMID- 1518037 TI - Correlation between cytotoxin production and sporulation in Clostridium difficile. AB - Correlation between cytotoxin production and sporulation was demonstrated when a Clostridium difficile culture was inoculated into fresh broth to give an initial count of less than 10 vegetative cells/ml with no spores. Under these conditions, cytotoxin was produced and released during sporulation. Addition of a sporulation inhibitor (acridine orange, 30 mg/L), resulted in a marked decrease in both sporulation and cytotoxin production, despite there being no change in the number of vegetative cells in the culture. These results indicate that sporulation might be closely related to cytotoxin production. PMID- 1518038 TI - Restricted distribution of Streptococcus milleri carbohydrate type antigens amongst other viridans streptococci. AB - The distribution of oral Streptococcus milleri carbohydrate type antigens in other viridans streptococcus species was examined. Rantz-Randall extracts of cells of the test strains grown in broth containing glucose were allowed to react with typing or grouping antisera for S. milleri serotypes a-k, or Lancefield groups A-G and K. Of 93 strains comprising more than 12 streptococcal species that included S. mutans and S. sanguis complexes, only 15 S. salivarius strains and one S. mitis strain were immunologically related to S. milleri serotype f. Unlike S. milleri strains, S. salivarius type f strains belonged to Lancefield group K, whereas the S. mitis strain was closely related to S. milleri serotype f but did not react with any of the Lancefield grouping antisera tested. Results suggest that oral S. milleri strains can be distinguished serologically from other oral viridans streptococci and that the typing antisera used in our researches might differentiate S. milleri isolates from the mouth from those associated with systemic purulent infections. PMID- 1518039 TI - Monoclonal antibodies to a 16-kDa antigen of Serpulina (Treponema) hyodysenteriae. AB - Monoclonal antibodies (MAbs) were produced to an outer-envelope preparation from Serpulina (Treponema) hyodysenteriae, the aetiological agent of swine dysentery. Three MAbs (isotype IgG1) were obtained. All three recognised a 16-kDa antigen that was common to most strains of S. hyodysenteriae of different serotypes but was absent from nonpathogenic, porcine intestinal spirochaetes. Immunofluorescence and immunogold labelling studies showed that the 16-kDa antigen was exposed on the surface of intact spirochaetes. The MAbs agglutinated freshly grown cultures of spirochaetes and inhibited growth of S. hyodysenteriae strains in vitro. PMID- 1518040 TI - In-vitro susceptibility of Giardia lamblia to albendazole, mebendazole and other chemotherapeutic agents. AB - The susceptibility of a strain of Giardia lamblia to benzimidazole carbamates, 5 nitroimidazoles, nitrofurans and other drugs was studied in vitro. Albendazole was the most active compound, with a 50% inhibitory concentration (IC50) of 0.01 mg/L and a minimal lethal concentration (MLC) of less than 0.04 mg/L; the IC50 of mebendazole was 0.06 mg/L and the MLC less than 0.5 mg/L. Among the 5 nitroimidazoles tested, ornidazole was the most effective (IC50 0.12 mg/L); tinidazole, metronidazole, secnidazole and hemezole were less active. Nifuroxazide, etofamide and nalidixic acid exhibited modest anti-giardial activity; quinfamide did not inhibit the growth of the parasite at a concentration of 200 mg/L. Albendazole and mebendazole are promising candidates for clinical use and should be further evaluated. PMID- 1518041 TI - Chromatin structure of Schizosaccharomyces pombe. A nucleosome repeat length that is shorter than the chromatosomal DNA length. AB - We have used new methods for chromatin isolation, together with conventional methods for measuring the nucleosome repeat length, to determine the repeat length of Schizosaccharomyces pombe chromatin. We obtain a result of 156(+/- 2) bp. Equivalent results are obtained using a psoralen crosslinking method for measuring the repeat length in viable spheroplasts. That result, together with other control experiments, rules out many possible artifacts. The measured value of 156(+/- 2) bp is smaller than the length of DNA found in the chromatosome. Thus, the chromatosome cannot be the fundamental unit of chromatin structure in all eukaryotes. The crossed linker model of chromatin higher order structure is incompatible with a nucleosome repeat length of 156 bp, and thus cannot apply to all eukaryotes. The solenoid model of higher order structure is compatible with this repeat length only if the solenoid is right-handed. We note two other properties of this chromatin. (1) Early in digestion, the DNA length of mononucleosomes from S. pombe and Aspergillus nidulans exceeds the nucleosome repeat length. (2) Many methods for isolating chromatin from S. pombe yield an apparent nucleosome repeat length of less than or equal to 140 bp; this result is found to be an artifactual consequence of nucleosome sliding. PMID- 1518042 TI - Effect of sequence mutations on the higher order structure of the yeast 5 S rRNA. AB - Mutant yeast ribosomal 5 S RNAs were probed by enzymatic cleavage and chemical reactivity to define further the higher order structure. Mutations that destabilized helix IV resulted in an altered tertiary structure in which a reduced reactivity to ethylnitrosourea at U90 and G91 could be correlated with greater enzymatic and Fe(II)-EDTA cleavages in helices II and V. The results provide direct evidence for, and a further definition of, a structural juxtaposition between helix II and the end of helix IV and indicate that, in contrast to earlier suggestions, the remaining tertiary structure is sufficiently stable to prevent "pseudoknot-like" interactions between helices III and IV. The data are fully consistent with the "lollipop" model of the tertiary structure. PMID- 1518043 TI - Sporulation regulatory protein GerE from Bacillus subtilis binds to and can activate or repress transcription from promoters for mother-cell-specific genes. AB - The mother-cell line of gene expression during sporulation in Bacillus subtilis is a hierarchical cascade consisting of at least four temporally controlled gene sets, the first three of which each contain a regulatory gene for the next gene set in the pathway. gerE, a member of the penultimate gene set, is a regulatory gene whose products is required for the transcriptional activation of genes (coat protein genes cotB and cotC) in the last gene set. The gerE product also influences the expression of other members of the penultimate gene set (coat protein genes cotA and cotD appear to be repressed and activated, respectively). We now report that the purified product of gerE (GerE) is a DNA-binding protein that adheres to the promoters for cotB and cotC. We also show that GerE stimulates cotB and cotC transcription in vitro by RNA polymerase containing the mother-cell sigma factor sigma K. These findings support the view that GerE is a positively acting, regulatory protein whose appearance at a late stage of development directly activates the transcription of genes in the last known temporal class of mother-cell-expressed genes. In addition, GerE stimulates cotD transcription and inhibits cotA transcription in vitro by sigma K RNA polymerase, as expected from in vivo studies, and, unexpectedly, profoundly inhibits in vitro transcription of the gene (sigK) that encodes sigma K. The effects of GerE on cotD and sigK transcription are just the opposite of the effects exerted by the earlier-appearing, mother-cell regulatory protein spoIIID, suggesting that the ordered appearance of first SpoIIID, then GerE, ensures proper flow of the regulatory cascade controlling gene expression in the mother cell. PMID- 1518044 TI - Sequences of 20 subunits of NADH:ubiquinone oxidoreductase from bovine heart mitochondria. Application of a novel strategy for sequencing proteins using the polymerase chain reaction. AB - NADH:ubiquinone oxidoreductase, the first enzyme in the respiratory electron transport chain of mitochondria, is a membrane-bound multi-subunit assembly, and the bovine heart enzyme is now known to contain about 40 different polypeptides. Seven of them are encoded in the mitochondrial DNA; the remainder are the products of nuclear genes and are imported into the organelle. The primary structures of 12 of the nuclear coded subunits have been described and those of a further 20 are described here. The subunits have been sequenced by following a strategy based on the polymerase chain reaction. This strategy has been tailored from existing methods with the twofold aim of avoiding the use of cDNA libraries, and of obtaining a cDNA sequence rapidly with minimal knowledge of protein sequence, such as can be determined in a single N-terminal sequence experiment on a polypeptide spot on a two-dimensional gel. The utility and speed of this strategy have been demonstrated by sequencing cDNAs encoding 32 nuclear-coded membrane associated proteins found in bovine heart mitochondria, and the procedures employed are illustrated with reference to the cDNA sequence of the 20 subunits of NADH:ubiquinone oxidoreductase that are presented. Extensive use has also been made of electrospray mass spectrometry to measure molecular masses of the purified subunits. This has corroborated the protein sequences of subunits with unmodified N terminals, and their measured molecular masses agree closely with those calculated from the protein sequences. Nine of the subunits, B8, B9, B12, B13, B14, B15, B17, B18 and B22 have modified alpha-amino groups. The measured molecular masses of subunits B8, B13, B14 and B17 are consistent with the post-translational removal of the initiator methionine and N-acetylation of the adjacent amino acid. The initiator methionine of subunit B18 has been removed and the N-terminal glycine modified by myristoylation. Subunits B9 and B12 appear to have N-terminal and other modifications of a hitherto unknown nature. The sequences of the subunits of bovine complex I provide important clues about the location of iron-sulphur clusters and substrate and cofactor binding sites, and give valuable information about the topology of the complex. No function has been ascribed to many of the subunits, but some of the sequences indicate the presence of hitherto unsuspected biochemical functions. Most notably the identification of an acyl carrier protein in both the bovine and Neurospora crassa complexes provides evidence that part of the complex may play a role in fatty acid biosynthesis in the organelle, possibly in the formation of cardiolipin.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1518045 TI - New triple-helical model for the shaft of the adenovirus fibre. AB - The adenovirus fibre is a trimeric protein with a globular head on a long thin shaft that projects from the twelve fivefold vertices of the virion. The shaft region of the fibre primary sequence has a unique pseudo-repeating motif of 15 residues. Using constraints derived from sequence analysis, the trimeric nature of the fibre, the experimental determination of the shaft length and general knowledge about protein structure, an atomic model of the fibre shaft has been constructed by computer modelling techniques. In the final model the three monomers form a left-handed triple-helical structure with threefold symmetry and with successive 15-residue repeats on the same chain related by an axial rise of 13.1 A and a left-handed azimuthal rotation of close to 300 degrees. Three threefold related beta-sheets with short strands are formed by inter-monomer main chain hydrogen bonds giving rise to superhelical ribbons covering the surface of the shaft. The model satisfies criteria of extensive hydrogen bonding, reasonable backbone torsion angles, burial of most hydrophobic residues and good packing of the hydrophobic core. Furthermore, the model is consistent with the observed shaft length of about 290 A and its calculated X-ray fibre diffraction patterns shows the characteristic features found in the diffraction pattern of crystals of fibre, notably layer lines with a spacing of about 1/26 A-1 and strong meridional intensity at 1/4.4 A-1. PMID- 1518046 TI - Refined 2.3 A X-ray crystal structure of bovine thrombin complexes formed with the benzamidine and arginine-based thrombin inhibitors NAPAP, 4-TAPAP and MQPA. A starting point for improving antithrombotics. AB - Well-diffracting crystals of bovine epsilon-thrombin in complex with several "non peptidic" benzamidine and arginine-based thrombin inhibitors have been obtained by co-crystallization. The 2.3 A crystal structures of three complexes formed either with NAPAP, 4-TAPAP, or MQPA, were solved by Patterson search methods and refined to crystallographic R-values of 0.167 to 0.178. The active-site environment of thrombin is only slightly affected by binding of the different inhibitors; in particular, the exposed "60-insertion loop" essentially maintains its typical projecting structure. The D-stereoisomer of NAPAP and the L stereoisomer of MQPA bind to thrombin with very similar conformations, as previously inferred from their binding to bovine trypsin; the arginine side-chain of the latter inserts into the specificity pocket in a "non-canonical" manner. The L-stereoisomer of 4-TAPAP, whose binding geometry towards trypsin was only poorly defined, is bound to the thrombin active-site in a compact conformation. In contrast to NAPAP, the distal p-amidino/guanidino groups of 4-TAPAP and MQPA do not interact with the carboxylate group of Asp189 in the thrombin specificity pocket in a "symmetrical" twin N-twin O manner, but through "lateral" single N twin O contacts; in contrast to the p-amidino group of 4-TAPAP, however, the guanidyl group of MQPA packs favourably in the pocket due to an elaborate hydrogen bond network, which includes two entrapped water molecules. These thrombin structures confirm previous conclusions of the important role of the intermolecular hydrogen bonds formed with Gly216, and of the good sterical fit of the terminal bulky hydrophobic inhibitor groups with the hydrophobic aryl binding site and the S2-cavity, respectively, for tight thrombin active site binding of these non-peptidic inhibitors. These accurate crystal structures are presumed to be excellent starting points for the design and the elaboration of improved antithrombotics. PMID- 1518047 TI - Three-dimensional structure in solution of acyl-coenzyme A binding protein from bovine liver. AB - The three-dimensional structure of acyl-coenzyme A binding protein as encoded by the recombinant gene in Escherichia coli has been determined using nuclear magnetic resonance (n.m.r.) spectroscopy. The structure consists of four alpha helices A1 (residues 3 to 15), A2 (residues 20 to 36), A3 (residues 51 to 60), and A4 (residues 65 to 85). A1 and A4, and A2 and A3, run in parallel pairs. A2 runs anti-parallel to A1 and A4. The three-dimensional structure of the protein is reminiscent of a shallow bowl with a rim. The "rim" is characterized by many polar and charged groups, whereas the inside and outside surface is predominantly hydrophobic with patches of uncharged polar hydroxyl groups of threonyl, serinyl and tyrosyl residues. The inside bottom contains through two epsilon-amino groups of lysine residues (Lys13 and Lys32) suggesting that the binding site for the nucleotide part of the acyl-coenzyme A part of the ligand molecule is at the inside surface of the bowl. The structure determination was done on the basis of measurements of the intensities of nuclear Overhauser effects (NOEs) and coupling constants that were translated into interatom distance restraints for 833 atom pairs, and 87 dihedral angle restraints, of which 23 were in chiral centers. In all, 42 hydrogen bonds were identified by n.m.r. and provided an additional 84 distance restraints. A total of 20 structures were calculated and the structures can be aligned to a root-mean-square deviation of 0.5 A for the backbone atoms of the residues in the four helices. A region of six residues could not be defined by the restraints obtained by n.m.r. The program Pronto was used for the spectrum analysis in general, and especially for the assignment of the individual NOEs, the integration of the cross peaks, and the measurements of the coupling constants. The programs DIANA and X-PLOR have been used in the structure calculations and evaluations. PMID- 1518048 TI - Hydrogen bonding in globular proteins. AB - A global census of the hydrogen bonds in 42 X-ray-elucidated proteins was taken and the following demographic trends identified: (1) Most hydrogen bonds are local, i.e. between partners that are close in sequence, the primary exception being hydrogen-bonded ion pairs. (2) Most hydrogen bonds are between backbone atoms in the protein, an average of 68%. (3) All proteins studied have extensive hydrogen-bonded secondary structure, an average of 82%. (4) Almost all backbone hydrogen bonds are within single elements of secondary structure. An approximate rule of thirds applies: slightly more than one-third (37%) form i----i--3 hydrogen bonds, almost one-third (32%) form i----i--4 hydrogen bonds, and slightly less than one-third (26%) reside in paired strands of beta-sheet. The remaining 5% are not wholly within an individual helix, turn or sheet. (5) Side chain to backbone hydrogen bonds are clustered at helix-capping positions. (6) An extensive network of hydrogen bonds is present in helices. (7) To a close approximation, the total number of hydrogen bonds is a simple function of a protein's helix and sheet content. (8) A unique quantity, termed the reduced number of hydrogen bonds, is defined as the maximum number of hydrogen bonds possible when every donor:acceptor pair is constrained to be 1:1. This quantity scales linearly with chain length, with 0.71 reduced hydrogen bond per residue. Implications of these results for pathways of protein folding are discussed. PMID- 1518049 TI - Molecular structure of the B-DNA dodecamer d(CGCAAATTTGCG)2. An examination of propeller twist and minor-groove water structure at 2.2 A resolution. AB - The crystal structure of the dodecanucleotide duplex d(CGCAAATTTGCG)2 has been solved to 2.2 A resolution and refined to an R-factor of 18.1% with the inclusion of 71 water molecules. The structure shows propeller twists of up to -20 degrees for the A.T base-pairs, although there is probably only one (weak) three-centre hydrogen bond in the six base-pair AT narrow minor-groove region. An extensive ribbon of hydration has been located in this groove that has features distinctive from the classic "spine of hydration". Solvation around phosphate groups is described, with several instances of water molecules bridging between phosphates. PMID- 1518050 TI - Structure of RecA-DNA complexes studied by combination of linear dichroism and small-angle neutron scattering measurements on flow-oriented samples. AB - By combining anisotropy of small-angle neutron scattering (SANS) and optical anisotropy (linear dichroism, l.d.) on flow-oriented RecA-DNA complexes, the average DNA-base orientation has been determined in RecA complexes with double stranded (ds) as well as single-stranded (ss) DNA. From the anisotropy of the two dimensional SANS intensity representation, the second moment orientation function S is obtained. Knowledge of S is crucial for the interpretation of l.d. spectra in terms of orientation of the DNA bases and the aromatic amino acid residues. The DNA-base planes are essentially perpendicular to the fibre axis of the complex between RecA and dsDNA in the presence of cofactor ATP gamma S. A somewhat tilted base geometry is found for the RecA-ATP gamma S complexes with single-stranded poly(dT) and poly(d epsilon A). This behaviour contrasts the RecA ssDNA complex formed without cofactor which displays a poor orientation of the bases. Well-ordered bases in the ssDNA-RecA complex is possibly reflecting the role of RecA in preparing a nucleotide strand for base-pairing in the search-for homology process. While the central SANS intensity is essentially independent of the pitch of the helical complex, a secondary intensity maximum, which becomes focused upon flow orientation, is found to be a sensitive measure of the pitch. The pitch values for the complexes compare well with cryo-electron microscopy results but are slightly larger than those seen for uranyl-stained samples. PMID- 1518051 TI - Structure of DNA-RecA complexes studied by residue differential linear dichroism and fluorescence spectroscopy for a genetically engineered RecA protein. AB - The structure of complexes of RecA with double-stranded and single-stranded DNA was studied by linear dichroism spectroscopy, fluorescence quenching and fluorescence anisotropy measurements. One of the two tryptophan residues (Trp291) of RecA was replaced by genetic engineering for an ultraviolet light-transparent threonine. This modified RecA protein shows, within experimental errors, the same DNA-binding kinetics and stoichiometry as the wild-type protein and no significant variation with respect to in vivo repair function was observed between cells with the two protein forms. By comparing the dichroic and fluorescence properties of the wild-type versus the modified protein, when bound to DNA, information about orientation and environment of the Trp291 chromophore in the complex could be obtained. The indole chromophore of Trp291Z was found to be oriented with its pseudo-long axis tilted 61 degrees and the aromatic plane is tilted 27 degrees relative to the fibre axis. Trp291 shows low mobility within the protein and therefore the deduced orientation may be used as a "handle" on the protein at the construction of three-dimensional models of RecA-DNA complexes. Comparison with the orientation for this residue in the crystal structure of the RecA homopolymer fibre indicates no measurable reorientation of the C-terminal subdomain of RecA upon DNA binding. Whereas the accuracy of the orientation determination of tryptophan, in absolute terms, is rather poor, changes of its orientation can be detected with high precision. Thus, similar Trp291 orientations are obtained in the complexes with single-stranded and double stranded DNA, indicating similar structures of the protein fibres. The fluorescence quenching results indicate that the protein region of Trp291 is not involved in the binding of DNA. PMID- 1518052 TI - Crystal structure of cleaved equine leucocyte elastase inhibitor determined at 1.95 A resolution. AB - The crystal structure of active-site cleaved equine leucocyte elastase inhibitor, a member of the serpin superfamily, has been solved and refined to a crystallographic R-factor of 17.6% at 1.95 A resolution. Despite being an intracellular inhibitor with rather low sequence homology of 30% to human alpha 1 antichymotrypsin and alpha 1-proteinase inhibitor, the three-dimensional structures are very similar, with deviations only at the sites of insertions and few mobile secondary structure elements. The better resolution in comparison with the structures of other cleaved serpins allows a more precise description of the so-called R-state of the serpins. PMID- 1518054 TI - X-ray structure of the DNase I-d(GGTATACC)2 complex at 2.3 A resolution. AB - The crystal structure of a complex between DNase I and the self-complementary octamer duplex d(GGTATACC)2 has been solved using the molecular replacement method and refined to a crystallographic R-factor of 18.8% for all data between 6.0 and 2.3 A resolution. In contrast to the structure of the DNase I d(GCGATCGC)2 complex solved previously, the DNA remains uncleaved in the crystal. The general architecture of the two complexes is highly similar. DNase I binds in the minor groove of a right-handed DNA duplex, and to the phosphate backbones on either side over five base-pairs, resulting in a widening of the minor groove and a concurrent bend of the DNA away from the bound enzyme. There is very little change in the structure of the DNase I on binding the substrate. Many other features of the interaction are conserved in the two complexes, in particular the stacking of a deoxyribose group of the DNA onto the side-chain of a tyrosine residue (Y76), which affects the DNA conformation and the binding of an arginine side-chain in the minor groove. Although the structures of the DNA molecules appear at first sight rather similar, detailed analysis reveals some differences that may explain the relative resistance of the d(GGTATACC)2 duplex to cleavage by DNase I: whilst some backbone parameters are characteristic of a B conformation, the spatial orientation of the base-pairs in the d(GGTATACC)2 duplex is close to that generally observed in A-DNA. These results further support the hypothesis that the minor-groove width and depth and the intrinsic flexibility of DNA are the most important parameters affecting the interaction. The disposition of residues around the scissile phosphate group suggests that two histidine residues, H134 and H252, are involved in catalysis. PMID- 1518053 TI - Thermal motions of surface alpha-helices in the D-galactose chemosensory receptor. Detection by disulfide trapping. AB - The D-galactose chemosensory receptor of Escherichia coli is a .32 kDa globular protein possessing two distinct structural domains, each organized in an alpha/beta folding motif. Helices I and X lie at adjacent approximately parallel positions on the surface of the N-terminal domain, near the hinge region. In order to analyze the relative thermal motions of these two helices, the present study utilizes a generalizable disulfide trapping approach: first, site-directed mutagenesis is used to place a pair of cysteine residues at locations of interest on the protein surface, then disulfide bond formation is used to trap intramolecular cysteine-cysteine collisions resulting from thermal motions. Specifically, four engineered di-cysteine receptors have been constructed, each possessing one cysteine at position 26 on helix I, and a second cysteine at varying positions on helix X. A fifth control receptor possesses one cysteine at position 26, and a second on the opposite surface of the molecule. These surface cysteine substitutions have little or no effect on the measurable receptor parameters as judged by ligand binding equilibria and kinetics, protein stability, and 19F nuclear magnetic resonance, indicating that the engineered receptors are useful probes of native backbone dynamics. Spatial and kinetic features of backbone motions have been investigated by measuring intramolecular disulfide formation rates for cysteine pairs in the fully liganded receptor. The resulting rates decrease monotonically with increasing distance between cysteines in the crystal structure, while no disulfide formation is observed for the control pair unless the molecule is unfolded. The minimum translational amplitudes of the observed backbone motions range from 4.5 to 15.2 A, and the minimum rotational amplitudes are as large as 35 degrees. For each motion the rate of intramolecular sulfhydryl-sulfhydryl collision has been estimated from the measured rate of disulfide formation: the 4.5 and 15.2 A translations yield approximately 10(4) and approximately 10 collisions s-1 molecule-1, respectively. These collision rates, which are faster than ligand dissociation, likely underestimate the actual motional frequencies since only an undetermined fraction of the total motions yield collisions. The simplest plausible trajectory capable of producing such collisions is a rate-limiting translation of one or both helices along their long axes, coupled with minor helix rotations. When sugar is removed from the receptor, a substantial increase in backbone dynamics is observed, indicating the presence of new long-range backbone trajectories. Overall, the results suggest that internal motions in proteins may have larger amplitudes than previously observed. PMID- 1518055 TI - Contacts between Tet repressor and tet operator revealed by new recognition specificities of single amino acid replacement mutants. AB - We have analyzed the DNA binding properties of Tet-repressor mutants with single amino acid residue replacements at eight positions within the alpha-helix-turn alpha-helix DNA-binding motif. A saturation mutagenesis of Gln38, Pro39, Thr40, Tyr42, Trp43 and His44 in the second alpha-helix was performed; in addition, several substitutions of Thr27 and Arg28 in the first alpha-helix were constructed. The abilities of these mutant repressors to bind a set of 16 operator variants were determined and revealed 23 new binding specificities. All repressor mutants with DNA-binding activity were inducible by tetracycline, while mutants lacking binding activity were trans-dominant over the wild-type. All mutant proteins were present at the same intracellular steady-state concentrations as the wild-type. These results suggest the structural integrity of the mutant repressors. On the basis of the new recognition specificities, five contacts between a repressor monomer and each operator half-site and the chemical nature of these repressor-operator interactions are proposed. We suggest that Arg28 contacts guanine of the G.C base-pair at operator position 2 with two H bonds, Gln38 binds adenine of the A.T base-pair at position 3 with two H-bonds, and the methyl group of Thr40 participates in a van der Waals' contact with cytosine of the G.C base-pair at position 6 of tet operator. A previously unrecognized type of interaction is proposed for Pro39, which inserts its side chain between the methyl groups of the thymines of T.A and A.T base-pairs at positions 4 and 5. Computer modeling of these proposed contacts reveals that they are possible using the canonical structures of the helix-turn-helix motif and B DNA. These contacts suggest an inverse orientation of the Tet repressor helix turn-helix with respect to the operator center as compared with non-inducible repressor-operator complexes, and are supported by similar contacts of other repressor-operator complexes. PMID- 1518056 TI - Crystallization and preliminary crystallographic characterization of GTP cyclohydrolase I from Escherichia coli. AB - GTP cyclohydrolase I of Escherichia coli has been purified from a recombinant bacterial strain. The enzyme was crystallized from 0.6 M-sodium citrate and from 0.8 M-sodium/potassium phosphate, respectively. Crystals grown in citrate showed X-ray diffraction extending to a resolution better than 3 A. The space group was P2(1) with cell dimensions a = 204.8 A, b = 210.1 A, c = 72.2 A, alpha = gamma = 90 degrees and beta = 95.8 degrees. PMID- 1518057 TI - Crystallization and preliminary crystallographic studies of glucosamine-6 phosphate deaminase from Escherichia coli K12. AB - Hexameric glucosamine-6-phosphate deaminase from Escherichia coli has been crystallized isomorphously with both phosphate and ammonium sulphate as precipitants, over a wide pH range (6.0 to 9.0). The crystals belong to space group R32 and the cell parameters in the hexagonal setting are a = b = 125.9 A and c = 223.2 A. A complete native data set was collected to 2.1 A resolution. Self-rotation function studies suggest that the hexamers sit on the 3-fold axis and have point group symmetry 32, with a non-crystallographic dyad relating two monomers linked by an interchain disulfide bridge. A possible packing for the unit cell is proposed. PMID- 1518058 TI - Purification, crystallization and preliminary crystallographic study of neuraminidase from Vibrio cholerae and Salmonella typhimurium LT2. AB - The nanH genes of Vibrio cholerae and Salmonella typhimurium LT2 coding neuraminidase were cloned separately in Escherichia coli, and the expression products purified. Single crystals of the V. cholerae neuraminidase were obtained using the hanging drop vapour diffusion method with polyethylene glycol as precipitant at pH 7.2. The crystals belong to the orthorhombic space group P2(1)2(1)2(1), with unit cell dimensions a = 71.9 A, b = 79.0 A, c = 165.7 A, and with one molecule in the asymmetric unit. Diffraction extends to at least 2.5 A. Single crystals of the S. typhimurium neuraminidase were obtained by hanging drop with potassium phosphate as precipitant at pH 7.2. The crystals also belong to the orthorhombic space group P2(1)2(1)2(1), with unit cell dimensions a = 47.4 A, b = 82.8 A, c = 92.4 A, and with one molecule in the asymmetric unit. Diffraction extends to at least 1.8 A. PMID- 1518059 TI - Crystallization and preliminary X-ray diffraction studies of aspartic proteinase from Irpex lacteus. AB - Crystals of ILAP (Irpex lacteus aspartic proteinase) have been obtained by the hanging drop method using ammonium sulfate as a precipitant. The crystals are monoclinic, space group P2(1) with cell dimensions a = 54.5 A, b = 79.6 A, c = 37.5 A, beta = 96.8 degrees. The crystals are quite stable to X-rays and diffract beyond 1.9 A resolution. There is one molecule in the asymmetric unit. PMID- 1518060 TI - Primary structure of the second largest subunit of human RNA polymerase II (or B). AB - The cDNA of the second largest subunit of RNA polymerase II (or B) from HeLa cells has been cloned and sequenced. A predicted amino acid sequence of 1174 residues (calculated molecular mass of 133,896 Da) was derived from the longest open reading frame and compared to the sequences of homologous subunits of polymerases of eukaryotic, archaeal and bacterial origin. After optimal alignment, about 16% of the residues were found to be conserved throughout evolution, from human to Escherichia coli. About 2/3 of the overall length of the conserved domains delineated by these residues are clustered within the C terminal half of the human polypeptide, whereas the remaining is spread over its N-terminal half. The putative functional significance of these conserved domains is discussed. PMID- 1518061 TI - Refined 2.5 A structure of murine adenosine deaminase at pH 6.0. AB - The X-ray structure of murine adenosine deaminase complexed with the transition state analogue 6-hydroxyl-1,6-dihydropurine ribonucleoside has been determined from a single crystal grown at pH 4.2 and transferred to mother liquor of increasing pH up to a final pH of 6.0 prior to data collection. The structure has been refined to 2.5 A to a final crystallographic R-factor of 20% using phases from the previously refined 2.4 A structure at pH 4.2. Kinetic measurements show that the enzyme is only 20% active at pH 4.2 whereas it is fully active between pH 6.0 and pH 8.5. The refined structures at either pH are essentially the same. Consideration of the pKa values of the key catalytic residues and the mechanism proposed on the basis of the structure suggests that the ionization state of these residues is largely responsible for the pH dependence on activity. PMID- 1518062 TI - Protein-ligand energetics assessed using deoxy and fluorodeoxy sugars in equilibrium binding and high resolution crystallographic studies. AB - Hydrogen bonding interactions are one of the most important single factors in protein-ligand interactions and molecular recognition. To probe the energetics of the interactions, we have analyzed the binding of 1-deoxy-, 2-deoxy- and 6-fluoro 6-deoxy- analogues of D-galactose (Gal) to a primary high-affinity periplasmic receptor for monosaccharide active transport. Kd values and atomic structures refined at 1.81 to 1.45 A resolution of the complexes have been determined and compared with those of Gal binding. With binding site residues and the bound modified sugars in nearly identical positions as found in the complex with Gal, the binding of 1-deoxy-Gal or 2-deoxy-Gal reflects the overall contribution of 1.8 kcal mol-1 per hydrogen bond (neutral-charge type) to the affinity of Gal. Neglected in these estimates is the contribution of van der Waals' forces that accompany the formation of hydrogen bonds with each sugar hydroxyl. Contrary to expectations, the 6-fluoro-6-deoxy analogue proved to be an inadequate probe of Gal OH6 as a hydrogen bond donor due to the binding of a new water molecule and structural changes arising from the electronegative fluoro group. This study sheds new light on the energetics of protein-ligand interactions and the use of engineered ligands in assessing these interactions. PMID- 1518063 TI - Non-competitive inhibition of group I intron RNA self-splicing by aminoglycoside antibiotics. AB - Aminoglycoside antibiotics inhibit self-splicing of group I intron RNA in vitro at concentrations as low as 10(-6) M. The sites of interaction and the mechanism of inhibition have yet to be determined. A comparative study of inhibition by different 2-deoxystreptamine analogues reveals structural features of the aminoglycoside antibiotics required for their interaction and effect on group I introns. Complete antibiotic inhibition of the two steps of splicing was not reversed at high concentrations of guanosine, indicating a non-competitive inhibition. A mutant group I intron in which the conserved guanosine nucleotide of the G-binding site had been replaced by an adenosine, was sensitive to the antibiotics providing direct evidence that the antibiotics do not interact with the G-binding site in the same way as the guanine base. In addition kinetic analyses of the self-splicing process in the presence of antibiotic inhibitors supported a non-competitive mechanism of the mixed type for inhibition of the ribozyme. PMID- 1518064 TI - Cell-cycle control of a cloned chromosomal origin of replication from Caulobacter crescentus. AB - Caulobacter crescentus cell division is asymmetric and yields distinct swarmer cell and stalked cell progeny. Only the stalked cell initiates chromosomal replication, and the swarmer cell must differentiate into a stalked cell before chromosomal DNA replication can occur. In an effort to understand this developmental control of replication, we employed pulsed-field gel electrophoresis to localize and to isolate the chromosomal origin of replication. The C. crescentus homologues of several Escherichia coli genes are adjacent to the origin in the physical order hemE, origin, dnaA and dnaK,J. Deletion analysis reveals that the minimal sequence requirement for autonomous replication is greater than 430 base-pairs, but less than 720 base-pairs. A plasmid, whose replication relies only on DNA from the C. crescentus origin of replication, has a distinct temporal pattern of DNA synthesis that resembles that of the bona fide C. crescentus chromosome. This implies that cis-acting replication control elements are closely linked to this origin of replication. This DNA contains sequence motifs that are common to other bacterial origins, such as five DnaA boxes, an E. coli-like 13-mer, and an exceptional A + T-rich region. Point mutations in one of the DnaA boxes abolish replication in C. crescentus. This origin also possesses three additional motifs that are unique to the C. crescentus origin of replication: seven 8-mer (GGCCTTCC) motifs, nine 8-mer (AAGCCCGG) motifs, and five 9-mer (GTTAA-n7-TTAA) motifs are present. The latter two motifs are implicated in essential C. crescentus replication functions, because they are contained within specific deletions that abolish replication. PMID- 1518065 TI - Novel Escherichia coli mutant, dnaR, thermosensitive in initiation of chromosome replication. AB - A newly isolated Escherichia coli mutant thermosensitive in DNA synthesis had an allele named dnaR130, which was located at 26.3 minutes on the genetic map. The mutant was defective in initiation of chromosome replication but not in propagation at a high temperature. This mutant was capable of growing in the absence of the rnh function at the high temperature by means of a dnaA independent replication mechanism. In the mutant exposed to the high temperature, an oriC plasmid was able to replicate, although at a lower rate than at the low temperature. The plasmid replication at the high temperature depended on the dnaA function essential for the initiation of replication from oriC. The mutant lacking the rnh function persistently maintained the oriC plasmid at the high temperature in a dnaA-dependent manner. Thus, the dnaR function was required for initiation of replication of the bacterial chromosome from oriC but not the oriC plasmid. This result reveals that a dnaR-dependent initiation mechanism that is dispensable for oriC plasmid replication operates in the bacterial chromosome replication. PMID- 1518066 TI - Video-enhanced microscopy of organelle movement in an intact epithelium. AB - Digitally enhanced video microscopy has provided improved optical resolution in the study of intracellular organelle/particle movement, particularly in extruded axoplasm and certain thin single cell systems. We report here, for the first time, particle movement in an intact, isolated epithelium, the killifish proximal convoluted tubule. Cytoplasmic particles exhibited predominantly unidirectional linear movement approaching several microns in length, sometimes with multiple turns. The velocities of 34 particles measured in 11 cells averaged 0.29 microns/sec (range, 0.007-3.1 microns/sec). Microtubules--the well-established basis for organelle movement in cells--were present but were sparsely represented in electron micrographs of these cells. Video-enhanced microscopic techniques can now be applied to the study of organelle/particle movement in an intact epithelium. PMID- 1518067 TI - Morphology of the antennae of two species of biting midge: Culicoides impunctatus (Goetghebuer) and Culicoides nubeculosus (Meigen) (Diptera, Ceratopogonidae). AB - Scanning and transmission electron microscopy of the antennae of Culicoides impunctatus and Culicoides nubeculosus show that males and females share five sensillum types. Sensilla chaetica resemble mechanoreceptors, each innervated by a single neurone whose dendrite terminates distally in a tubular body: the arrangement of sensilla on male antennae suggests that females are located by sound. The antennae have both sharp- and blunt-tipped sensilla trichodea, sharp tipped sensilla on only the distal third and blunt-tipped sensilla on all subsegments. These sensilla are typical of olfactory receptors, having multiporous walls and being innervated by a number of neurones with bifurcating dendrites ascending the hair shafts. Sensilla basiconica occur on the distal five subsegments of the female antenna and the distal three subsegments of the male antenna. Sensilla coeloconica always occur on subsegment one and sometimes on a number of other subsegments, depending on sex and species. Both basiconic and coeloconic sensilla have double walls and unbranched dendrites and may be either olfactory or thermo- and/or hygroreceptors. All antennae except those of male C. impunctatus antennae have sensilla ampullacea, apparently deep-seated olfactory or thermoreceptors. Small peg sensilla fitting the description of contact chemoreceptors occur only at the tip of the male antenna. PMID- 1518068 TI - Intracytoplasmic ciliary elements in epidermal cells of Syndesmis echinorum and Paravortex cardii (Platyhelminthes, Dalyellioida). AB - Epidermal cells of Syndesmis echinorum and Paravortex cardii contain many intracytoplasmic ciliary components: clusters of centrioles disorganized and incomplete short axonemes composed of loosely organized microtubules of irregular lengths, fully formed axonemes though some with fewer than nine doublets, and ciliary rootlets. Furthermore, conspicuous dense granules are found in solitary groups in the cytoplasm. Clusters of dense granules are also closely associated with Golgi complexes and developing axonemal microtubules. Since the dense granules decrease in number as the axonemes increase, it is likely that the granules are involved in the formation of axonemal microtubules. Ciliary elements are especially abundant in epidermal cells of Paravortex cardii embryos, some of them resembling those previously described by several authors in differentiating ciliated cells engaged in centriologenesis and ciliogenesis. Attention has been focused on the relative proportion and position of these elements, as well as the different morphology and several assembling states that they exhibit in epidermal cells of adult S. echinorum and adults and embryos of P. cardii. A functional interpretation of some of the findings is given, which allows us to suggest a sequence of ciliogenetic events that occur in epidermal cells of both species. PMID- 1518069 TI - Retinoic acid enhances monoclonal antibody WE3 reactivity in the regenerate epithelium of the adult newt. AB - Monoclonal antibody (mAb) WE3 recognizes an antigen that is developmentally expressed in the wound epithelium during adult newt limb regeneration. Experiments were designed to determine whether retinoic acid (RA), dissolved in dimethyl sulfoxide (DMSO) and administered by intraperitoneal injection, would enhance the temporal appearance of the WE3 antigen. RA given on days 1 or 4 after amputation, when the WE3 antigen is not yet detectable, resulted in moderate reactivity to mAb 2 days after injection and strong reactivity throughout the wound epithelium 4 days after injection. DMSO alone had no enhancing effect. RA also caused limb skin epidermis to exhibit reactivity to mAb WE3, initially near the amputation level, but then also more proximally. By 4 and 6 days after RA injection, epidermis of the flank, eye lid, and unamputated hind limbs also became strongly reactive to mAb WE3. Outer layers of skin epidermis were shed, resulting in an epidermis only one or two cells thick. Epidermis of newts given DMSO alone remained non-reactive to mAb WE3. When RA was given on days 7 and 10 after amputation, when a low level of mAb WE3 reactivity is already present in the wound epithelium, a considerable enhancement of mAb WE3 reactivity occurred through the next few days. No such enhancement was seen with DMSO alone. RA also greatly increased mAb WE3 reactivity in the wound epithelium of denervated limbs, in which case the wound epithelial reactivity to mAb WE3 is normally low. Retinol palmitate also increased mAb WE3 reactivity. The results raise the possibility that the WE3 antigen is a component of most if not all retinoid target tissues in newts. PMID- 1518070 TI - Neuromuscular organization of feline anterior sartorius: II. Intramuscular length changes and complex length-tension relationships during stimulation of individual nerve branches. AB - The feline anterior sartorius is a long strap-like muscle composed of short muscle fibers. Nerve branches that enter this muscle contain the axons of motor units whose constituent muscle fibers are distributed asymmetrically within the muscle. In the present study, twitch and tetanic isometric contractions were evoked by stimulating individual nerve branches while muscle force was recorded and intramuscular length changes were monitored optically by the movement of reflective markers on the muscle. Contractions elicited by stimulating the parent nerve produced little change in the positions of the surface markers. Contractions elicited by stimulating the proximally or distally directed nerve branches caused the muscle to shorten at the end closest to the nerve branch and lengthen at the opposite end. Some muscles were supplied by a centrally directed nerve branch whose stimulation produced variable effects: in some cases a portion of the muscle shortened whereas the rest lengthened, but in other cases, the positions of the surface markers showed little change. The intramuscular length changes produced by stimulating single nerve branches were greater during isometric contractions at short whole-muscle lengths than at long whole-muscle lengths. The twitch and tetanic length-tension relationships obtained by stimulating the individual nerve branches were not congruent with the length tension relationship produced when the parent nerve was stimulated. At short whole-muscle lengths, stimulation of a single nerve branch generated only a small fraction of the force that could be generated by the muscle when the parent nerve was stimulated. As whole-muscle length increased, an increased fraction of total muscle force could be generated by stimulating a single nerve branch. The results suggest that a complex relationship between passive and active elements contributes to the total muscle force and depends on the distribution of active and passive muscle units throughout the muscle. PMID- 1518071 TI - Programmed cell death and heterolysis of larval epithelial cells by macrophage like cells in the anuran small intestine in vivo and in vitro. AB - The degenerative processes in the larval small intestine of Xenopus laevis tadpoles during spontaneous metamorphosis and during thyroid hormone-induced metamorphosis in vitro were examined by electron microscopy. Around the beginning of spontaneous metamorphic climax (stages 59-61), both apoptotic bodies derived from larval epithelial cells and intraepithelial macrophage-like cells suddenly increase in number. The macrophage-like cells become rounded and enlarged because of numerous vacuoles containing the apoptotic bodies. Mitotic profiles of the macrophage-like cells, however, are localized in the connective tissue where different developmental stages of macrophage-like cells are present. After stage 62, the intraepithelial macrophage-like cells decrease in number, while large macrophage-like cells which include the apoptotic bodies and retain intact cell membranes and nuclei appear in the lumen. Degenerative changes similar to those during spontaneous metamorphosis described above could be reproduced in vitro. In tissue fragments isolated from the small intestine of stage 57 tadpoles and cultured in the presence of thyroid hormone, the number of intraepithelial macrophage-like cells reaches its maximum around the 3rd day of cultivation when the larval epithelial cells most rapidly decrease in number. These results suggest that the rapid degeneration of larval epithelial cells occurs not only because of apoptosis of the epithelial cells themselves but also from heterolysis by macrophages. The macrophages probably originate in the connective tissue, actively proliferate, migrate into the larval epithelium around the beginning of metamorphic climax, and are finally extruded into the lumen. PMID- 1518072 TI - Ultrastructural and cytochemical aspects of oogenesis in Castrada viridis (Platyhelminthes, Rhabdocoela). AB - The heterocellular female gonad of the typhloplanoid Castrada viridis consists of a single germarium and two rows of vitellaria. The germarium, composed of a germinative zone and a growth zone, is surrounded externally by a layer of accessory cells the function of which is hypothesized in this study. The main feature of oocyte differentiation is the synthesis of small electron-dense inclusions produced by the rough endoplasmic reticulum (R.E.R.) and Golgi complex. The electron-dense content of the egg inclusions reacts positively to the cytochemical test used to detect polyphenols and is only partially extracted following incubation in protease. The genesis, composition, and peripheral location of egg inclusions in mature oocytes suggest that they could represent residual eggshell granules. The presumed function of eggshell granules is discussed and their fine morphology is compared with that observed in other neoophoran Platyhelminthes. PMID- 1518073 TI - Jaw-muscle activity in ferrets, Mustela putorius furo. AB - Electromyographical (EMG) activity was recorded bilaterally from the masseter and temporalis muscles of alert ferrets (Mustela putorius furo) during mastication and crushing. Electromyographic activity was also recorded during biting while a bite-force transducer placed between the carnassial teeth registered forces ranging from 1.5 to 48.8 N. Linear regression analysis demonstrates that temporalis and masseter EMG activity are linearly related to bite force. Electromyographic activity from the balancing-side muscles is nearly equal to EMG activity of the working-side muscles during bone crushing with the carnassial teeth. It is hypothesized that a high percentage of balancing-side muscle activity in ferrets can be recruited during carnassial biting because the postglenoid process prevents ventral displacement of the working-side mandibular condyle. PMID- 1518074 TI - Spatial and functional relationship between myocytes and fibroblasts in the rabbit sinoatrial node. AB - In an attempt to understand better the directional differences in conduction velocity in the rabbit sinoatrial node, a possible conductive role of the abundant connective tissue surrounding the myocytes has been investigated. In particular, starting from the finding of communicating junctions between heart muscle cells and fibroblasts in tissue culture, heterologous gap junctions were searched for in thin sections of the rabbit sinoatrial node. Within and at the edge of nodal cell clusters, fibroblasts often show thin sheet-like extensions parallel to the surface of myocytes. In contrast to the intimately contacting myocytes, fibroblast extensions are kept separated from the myocytes by the basement membrane of the latter. Besides some rare undefined membrane appositions a single tiny gap junction-like structure was found between a fibroblast and a myocyte in a tissue area in which the calculated number of gap junctions between myocytes amounts from 1.10(4) to 3.10(4). Yet, fibroblasts are linked together regularly by small gap junctions containing a wider gap than the junctions between the myocytes (1.4 +/- 0.4 nm vs. 1.0 +/- 0.4 nm, resp., P less than 0.05). As an alternative to direct electrical coupling, the possibility of interaction between fibroblasts and nodal cells by capacitive coupling has been considered. Model calculations based on the reconstruction of some fibroblast extensions parallel to nodal cells show that the current which can be transmitted from discharging nodal cells to fibroblasts is negligible. It is concluded that fibroblasts do not participate in the impulse conduction within the sinoatrial node. The origin of the directional differences in conduction velocity in the sinoatrial node must be found in the spatial arrangement of the myocytes and the distribution of the gap junctions between these cells only. PMID- 1518075 TI - Serum interleukin 6 levels become elevated in acute myocardial infarction. AB - We have examined serum interleukin 6 (IL-6) levels in 12 patients with acute myocardial infarction (AMI). IL-6 levels became elevated in all patients, following the rise of serum creatine kinase (CK) activity. Peak IL-6 levels showed a good correlation with peak serum C-reactive protein (CRP) levels, while there was no direct relationship between peak IL-6 levels and peak CK activity. IL-6 mRNA was not detected in unstimulated "quiescent" rat cardiocytes cultured in serum-free medium, but its expression was induced by exposure of the cells to serum or ionomycin. These results show that IL-6 is synthesized in the myocardium and serum IL-6 levels become elevated in AMI, suggesting that IL-6 could affect the progression and/or healing processes of AMI. PMID- 1518076 TI - Anti-ischaemic and endothelial protective actions of recombinant human osteogenic protein (hOP-1). AB - Osteogenic protein one (hOP-1), a member of the transforming growth factor-beta (TGF-beta) supergenic family, was studied for its anti-ischaemic properties in rats subjected to myocardial ischaemia and reperfusion. Ten minutes after ligation (i.e., just prior to reperfusion) of the left coronary artery, 2 or 20 micrograms/rat recombinant human (hOP-1) or its vehicle, was given intravenously. hOP-1 at 20 micrograms significantly reduced reperfusion injury 24 h later compared to rats receiving only vehicle (i.e., 0.9% NaCl). hOP-1 was also found to preserve rat coronary endothelial function (i.e., release of endothelium derived relaxing factor, EDRF) in perfused hearts following global ischaemia and reperfusion. Moreover, hOP-1 also significantly inhibited adherence of rat neutrophils to rat vascular endothelium in vitro. Thus, hOP-1 exerts significant anti-ischaemic effects. Some of this cardioprotection may be related to the ability of hOP-1 to preserve endothelial function and inhibit neutrophil adherence to the endothelium. PMID- 1518077 TI - Cultured vascular endothelial cell susceptibility to extracellularly generated oxidant injury. AB - To understand better the effect of oxidant injury on vascular endothelial cells, human saphenous vein endothelial cells were cultured at atmospheric (pO2 of 150 mmHg) or low (pO2 of 40 mmHg) oxygen tensions. The cellular rates of growth, antioxidant enzyme activities (superoxide dismutase, catalase, and glutathione peroxidase), phospholipid fatty acids and cellular susceptibility to extracellularly generated oxidants (hypoxanthine-xanthine oxidase) were measured. The antioxidant enzyme activities were regulated by oxygen tension and significantly differed by day 14. The cells cultured at the low oxygen tension had significantly (P less than 0.01) lower antioxidant activities than the cells cultured at the high oxygen tension. The cells cultured at an oxygen tension of 150 mmHg were more resistant to shrinkage and lipid peroxidation from the oxidants than the cells cultured at a pO2 of 40 mmHg by day 14. Since arterial and venous endothelial cells are perfused with blood at a pO2 of 100 and 40 mmHg, respectively, the postcapillary venous endothelial cells should have lower antioxidant enzyme activities than the precapillary arterial endothelial cells. PMID- 1518078 TI - Calcium transients in isolated cardiac myocytes are altered by 1,1,1 trichloroethane. AB - 1,1,1-Trichloroethane is a widely used solvent that is annually linked to several cases of sudden death following accidental exposure or abuse. Sudden death is believed to be due to ventricular fibrillation or myocardial depression. The purpose of this study was to investigate the mechanism of myocardial depression by assessing the influence of 1,1,1-trichloroethane on intracellular Ca transients in single neonatal rat ventricular myocytes using spectrofluorometric analysis of fura-2-Ca binding. Cells were exposed to 1,1,1-trichloroethane in Hanks' balanced salt solution aliquoted as a 0.2% DMSO solution by a single pass suffusion in an environmentally controlled chamber. 1,1,1-Trichloroethane (0.25 mM-8 mM) reduced the height of electrically (1 Hz, 60 V, 10 ms) induced Ca transients concentration dependently and reversibly to a maximum of about 50% with no effect on diastolic Ca concentration. Video motion analysis revealed an inhibition of contractility in the same concentration range. 1,1,1 Trichloroethane inhibited cytosolic Ca increase in response to KCl-induced (90 mM) depolarizations and further decreased the limited Ca transients in ryanodine (1 microM) pretreated myocytes. Increased external Ca (5 mM) antagonized the effect of 0.5 mM 1,1,1-trichloroethane on the Ca transients. 1,1,1 Trichloroethane reduced the caffeine (10 mM) releasable Ca pool in myocytes. These results show that 1,1,1-trichloroethane inhibits Ca mobilization during excitation-contraction coupling in ventricular myocytes. An inhibitory action on the influx of extracellular Ca as well as on sarcoplasmic reticulum Ca release and sequestration is likely to be responsible for this action. PMID- 1518079 TI - Differential regulation of insulin-like growth factor I by growth hormone and thyroid hormone in the heart of juvenile hypophysectomized rats. AB - Recent data suggest that the heart can act as both a source and target for the actions of polypeptide growth factors. Insulin-like growth factor I (IGF-I) is a polypeptide that has both mitogenic and differentiation properties that function at the autocrine/paracrine level, and has recently been demonstrated to be expressed in the heart. This knowledge, coupled with the observation that thyroid hormone (T3) promotes relative cardiac growth compared to the proportional increases in body and heart growth evoked by growth hormone (GH), lead us to speculate whether differential induction of cardiac IGF-I may account for the specialized trophic effects of T3 on the heart. Cardiac IGF-I gene expression was studied in an in vivo model in which cardiac growth in the hypophysectomized juvenile rat was stimulated with either GH, T3 or GH + T3. Two week infusions of T3 that resulted in cardiac growth, but no gain in body weight, resulted in a 4.6 fold increase in cardiac IGF-I mRNA levels compared to hypophysectomized controls. GH infusions that resulted in similar cardiac growth, but were accompanied by proportional body growth, had no effect on cardiac IGF-I mRNA levels. These data are the first to demonstrate stimulation of cardiac IGF-I mRNA levels by T3 and further support cardiac autocrine/paracrine actions for this polypeptide growth factor. PMID- 1518080 TI - The effects of a PAF antagonist on ischemic myocardial damage and arrhythmia in the dog. AB - Myocardial ischemia is associated with accumulation of lyso-phospholipids, including lyso-platelet activating factor, the degradation product and precursor of platelet activating factor. These compounds produce cellular and microvascular damage and, in the myocardium, depression of contractility and arrhythmia. The potent platelet activating factor antagonist, WEB 2086, or placebo, was infused (IV) 10 min before constriction of the proximal left anterior descending coronary artery in open-chest dogs. Two protocols were followed: the dose of WEB 2086 was 0.5 mg/kg in those subjected to 20 min ischemia with 10 min reperfusion (n = 40) and 5 mg/kg preceding 60 min ischemia alone (n = 24). There was no significant difference in the number of ventricular premature complexes between WEB 2086 and placebo treated dogs during either period of ischemia. On reperfusion in those surviving 20 min of ischemia, 5 of the 18 WEB 2086 and 9 of the 18 placebo treated dogs developed ventricular fibrillation (NS). After 60 min of myocardial ischemia, there was no statistical difference in histological changes (nuclear swelling, aggregation of chromatin, myofibrillar separation) between groups. Hence, no substantial effect of relatively large doses of WEB 2086 on ischemia induced histological change or arrhythmia was found in this preparation. PMID- 1518081 TI - Effects of oxygen free radicals on isolated cardiac myocytes from guinea-pig ventricle: electrophysiological studies. AB - Free oxygen radicals are formed during early reperfusion and are thought to contribute to some types of reperfusion abnormalities, including arrhythmias and myocardial stunning. The purpose of this study was to investigate electrophysiological effects of oxygen free radicals using voltage clamped single ventricular myocytes from guinea-pig hearts. Oxygen free radicals were produced enzymatically by the direct addition of xanthine oxidase (XOD, 0.04 U/ml) in the experimental chamber to a solution containing hypoxanthine (0.96 mM). The generation of oxygen radicals was confirmed by the formation of adrenochrome from adrenaline. Oxygen radicals caused automaticity of isolated myocytes within 20-30 min, followed by later hypercontracture. The percentage of rod-shaped cells declined sigmoidally as a function of time, with a half maximal value at 40.9 +/- 1.6 min, and a Hill slope of -0.10 +/- 0.01 (n = 26). These effects were prevented by a combination of superoxide dismutase (10(5) U/L) plus catalase (10(6) U/L). The rate at which cells underwent morphological shape changes was unchanged by ryanodine (0.5 microM) which is thought to act on the sarcoplasmic reticulum or by the Ca2+ channel blockers nisoldipine (1 microM) or Cd2+ (30 microM). Cellular automaticity and hypercontracture were delayed by variable degrees, and sometimes completely prevented, by zero (1 mM EGTA) extracellular Ca2+, MnCl2 (2 mM) and LaCl3 (50 microM), and amiloride (1 mM). On the other hand, in the presence of a low extracellular Na+ (30 mM) or caffeine (10 mM), hypercontracture occurred at a faster time scale. Whole cell voltage clamping revealed a decrease of the inward rectifying K+ current (IK1), and a decrease of the peak of the L-type Ca2+ current (ICa,L). The total ICa,L during the clamp step was increased, mainly because of an increased time constant of inactivation (47.6 +/- 4.7 ms to 72.7 +/- 15.5 ms after 30 min, n = 4, P less than 0.05). We conclude that oxygen radicals cause automaticity and hypercontracture of isolated myocytes, that these effects may be due to an increased intracellular Ca2+ concentration ([Ca2+]i), and despite an increased ICa,L, that the enhanced Ca2+ influx may occur predominantly via the Na/Ca exchange. PMID- 1518082 TI - Heterogeneity in the substitution process of amino acid sites of proteins coded for by mitochondrial DNA. AB - Several forms of maximum likelihood models are applied to aligned amino acid sequence data coded for in the mitochondrial DNA of six species (chicken, frog, human, bovine, mouse, and rat). These models range in form from relatively simple models of the type currently used for inferring phylogenetic tree structure to models more complex than those that have been used previously. No major discrepancies between the optimal trees inferred by any of these methods are found, but there are huge differences in adequacy of fit. A very significant finding is that the fit of any of these models is vastly improved by allowing a certain proportion of the amino acid sites to be invariant. An even more important, although disquieting, finding is that none of these models fits well, as judged by standard statistical criteria. The primary reason for this is that amino acid sites undergo substitution according to a process that is very heterogeneous. Because most phylogenetic inference is accomplished by choosing the optimal tree under the assumption that a homogeneous process is acting on the sites, the potential invalidity of some such conclusions is raised by this article's results. The seriousness of this problem depends upon the robustness of the phylogenetic inferential procedure to departures from the underlying model. PMID- 1518083 TI - Man's place in Hominoidea revealed by mitochondrial DNA genealogy. AB - Molecular biology has resurrected C. Darwin and T.H. Huxley's question about the origin of humans, but the precise branching pattern and dating remain controversial. To settle this issue, a large amount of sequence information is required. We determined mitochondrial (mt) DNA sequences for five hominoids; pygmy and common chimpanzees, gorilla, orangutan, and siamang. The common region compared with the known human sequence is 4759 bp long, encompassing genes for 11 transfer RNAs and 6 proteins. Because of the high substitution rates in mammalian mtDNA and an unprecedentedly large region compared, the sequence differences clearly indicate that the closest relatives to human are chimpanzees rather than gorilla. For dating the divergences of human, chimpanzee, and gorilla, we used only unsaturated parts of sequence differences in which the mtDNA genealogy is not obscured by multiple substitutions. The result suggests that gorilla branched off 7.7 +/- 0.7 million years (Myr) ago and human 4.7 +/- 0.5 Myr ago; the time difference between these divergences being as long as 3 Myr. PMID- 1518084 TI - Unusual organizational features of the Drosophila Gart locus are not conserved within Diptera. AB - The Drosophila Gart locus consists of two genes. One gene encodes three enzymes in the de novo purine nucleotide biosynthesis pathway [glycinamide ribonucleotide synthetase (GARS), aminoimidazole ribonucleotide synthetase (AIRS), and glycinamide ribonucleotide transformylase (GART)]. The second gene lies within an intron of the purine gene and encodes a cuticle protein. To investigate the evolution of the Gart locus, the Chironomus tentans homolog was cloned by screening a genomic DNA library with a polymerase chain reaction product. This study shows that the interesting structural features of this locus conserved in two distant Drosophila species are not found in the Chironomus homolog. These features include the cuticle protein gene nested within an intron and the existence of an alternative transcript to yield a monofunctional enzyme. In addition, the extremely rapid divergence of coding sequence seen for members of the tandemly duplicated AIRS domain in Drosophila is found to be much less rapid in Chironomus. PMID- 1518085 TI - Finite-state models in the alignment of macromolecules. AB - Minimum message length encoding is a technique of inductive inference with theoretical and practical advantages. It allows the posterior odds-ratio of two theories or hypotheses to be calculated. Here it is applied to problems of aligning or relating two strings, in particular two biological macromolecules. We compare the r-theory, that the strings are related, with the null-theory, that they are not related. If they are related, the probabilities of the various alignments can be calculated. This is done for one-, three-, and five-state models of relation or mutation. These correspond to linear and piecewise linear cost functions on runs of insertions and deletions. We describe how to estimate parameters of a model. The validity of a model is itself an hypothesis and can be objectively tested. This is done on real DNA strings and on artificial data. The tests on artificial data indicate limits on what can be inferred in various situations. The tests on real DNA support either the three- or five-state models over the one-state model. Finally, a fast, approximate minimum message length string comparison algorithm is described. PMID- 1518086 TI - A statistical test of hypotheses on the organization and origin of the genetic code. AB - Theories of the origin of the genetic code assign different weights to amino acid properties such as polarity and precursor-product relationship. Previous statistical work on the origin of the genetic code has produced controversial results. We analyze relationships between various amino acid and tRNA properties by one and the same statistical method. It is shown that polarities as well as precursor-product relationships are both likely to have been important in shaping the genetic code, together with codon swapping that left protein sequences intact. PMID- 1518087 TI - Patterns of nucleotide substitutions inferred from the phylogenies of the class I major histocompatibility complex genes. AB - Patterns of nucleotide substitutions in human major histocompatibility complex (MHC) class I genes were estimated by using phylogenetic trees of DNA sequences. The pattern is defined as a set of 12 parameters, each of which represents the relative frequency of substitutions from a particular nucleotide to another. The pattern at the antigen recognition sites (ARS) in functional MHC genes was remarkably different from that at the remaining coding region (non-ARS). In particular, the proportion of transitions among all the nucleotide substitutions (Ps) was extremely low at the third codon positions of ARS. In the HLA-A genes, Ps at the third codon positions was only 6% in ARS, whereas it was 69% in non ARS. In HLA-B, the corresponding values were 30% in ARS and 80% in non-ARS, respectively. On the other hand, Ps in a class I pseudogene (HLA-H) was 57%, which was in good agreement with Ps in other pseudogenes. Because pseudogenes are selectively neutral, the pattern in pseudogenes is regarded as the pattern of spontaneous substitution mutations. In general, the pattern in functional genes that are subject to selective forces deviates from the pattern in pseudogenes. At the third codon positions in coding regions, transitions scarcely cause amino acid replacements, whereas about half of transversions do cause replacements. Accordingly, Ps at the third codon positions decreases if amino acid replacements are accelerated by natural selection but increases if amino acids are conserved by functional constraint. Our observations imply that the ARS region is subject to natural selection favoring amino acid replacements, whereas the non-ARS region is subject to functional constraint. PMID- 1518088 TI - Conserved and variable repeat structures in the Balbiani ring gene family in Chironomus tentans. AB - The four Balbiani ring (BR) genes, BR1, BR2.1, BR2.2, and BR6 in the midge Chironomus tentans constitute a gene family encoding secretory proteins with molecular weights of approximately 10(6) daltons. The major part of each gene is known to consist of tandemly organized composite repeat units resulting in a hierarchic repeat arrangement. Here, we present the sequence organization of the 5' part of the BR2.2 and BR6 genes and describe the entire transcribed part of the two genes. As the BR1 and BR2.1 genes were also fully characterized recently, this allows the comparison of all genes in the BR gene family. All four genes share the same exon-intron structure and have evolved by gene duplications starting from a common ancestor, having the same overall organization as the BR genes of today. The genes encode proteins that have an approximately 10,000-amino acid residue extended central domain, flanked by a highly charged, approximately 200-residue amino-terminal domain and a globular 110-residue carboxy-terminal domain. Exons 1-3 and the beginning of exon 4 encode the amino-terminal domain, which throughout contains many regions built from short repeats. These repeats are often degenerate as to repeat unit and sequence and are present in different numbers between the genes. In several instances these repeat structures, however, are conserved at the protein level where they form positively or negatively charged regions. Each BR gene has a 26-38-kb-long exon 4, which consists of an array of 125-150 repeat units and encodes the central domain. The number of repeat units appears to be largely preserved by selection and all repeat units in the array are very efficiently homogenized. Occasionally variant repeats have been introduced, presumably from another BR gene by gene conversion, and spread within the array. Introns 1-3 at the 5' end of the genes have diverged extensively in sequence and length between the genes. In contrast, intron 4 at the 3' end is virtually identical between three of the four genes, suggesting that gene conversion homogenizes the 3' ends of the genes, but not the 5' ends. PMID- 1518089 TI - Evidence that mammalian glutamine-dependent carbamyl phosphate synthetase arose through gene fusion. AB - On the basis of homology, the mammalian CAD (glutamine-dependent carbamyl phosphate synthetase-aspartate transcarbamylase-dihydroorotase) gene appears to have arisen from the fusion of four separate ancestral genes. Evidence for two of these precursor genes is found in the carbamyl phosphate synthetase (CPSase) domain of CAD. In prokaryotes, such as Escherichia coli CPSase is encoded by two distinct cistrons of the carAB operon. Whereas carA and carB are separated by a short noncoding intercistronic region, the homologous sequences of the CAD gene encode an amino acid bridge. This bridge connects the subdomains of the CAD CPSase. We constructed a bacterial carAB fusion gene in which the intercistronic region codes for a hamster bridgelike sequence. The fused carAB gene directs the synthesis of a stable bifunctional polypeptide whose glutamine-dependent CPSase activity is comparable to the E. coli CPSase holoenzyme. The fusion in E. coli of the single gene counterparts of CAD demonstrates a potential model system to study the genetic events that lead to gene fusion and the creation of multienzymatic proteins. PMID- 1518090 TI - Phylogeny and evolutionary rates of G protein alpha subunit genes. AB - Rooted phylogenetic trees for a total of 34 genes encoding the stimulatory (s alpha), inhibitory (i alpha), transducin (t alpha), Gx (x alpha), Gz (z alpha), G11 (alpha 11), G12 (alpha 12), G13 (alpha 13), G16 (alpha 16), Gq (q alpha), and other (o alpha) G protein alpha subunits have been constructed. The analysis shows that the G12 (alpha 12 and alpha 13), Gq (alpha 11, alpha 16, and q alpha), and Gs (s alpha genes) groups form one cluster, and the Gx (x alpha and z alpha genes), G(i) (i alpha genes), Gt (t alpha 1 and t alpha 2), and G(o) (o alpha genes) groups form another cluster. During mammalian evolution, the rates of synonymous substitutions for these genes were estimated to be between 1.77 x 10( 9)/site/year and 5.63 x 10(-9)/site/year, whereas those of non-synonymous substitutions were between 0.008 x 10(-9)/site/year and 0.067 x 10(-9)/site/year. These evolutionary rates are similar to those for histone genes, suggesting equally important biological functions of the G protein alpha subunits. PMID- 1518091 TI - Statistical analysis and prediction of the exonic structure of human genes. AB - Nonhomologous fully sequenced human protein-coding genes were studied. Three sets of exon-exon junctions were formed defined by the intron (shadow) position relative to the reading frame. For the analysis of intron shadow signals in exons, information content and discrimination energy approaches were used with the correction allowing one to ignore the influence of a protein-coding message. The corrected formulas allow one to define the consensuses for the three types of intron shadow signals as a AG/guwn, cAG/GUnn, and cAG/gunU, and provide better recognition than the original formulas. The analysis of the codon usage in the signal positions leads to the conclusion that the prevalence of some amino acids in corresponding protein sites is caused by the signal requirements and not vice versa. The distribution of potential intron shadow signals in exons contradicts the hypothesis of intron insertion into suitable preexisting sites. There exists a correlation between the intron types and/or the exon length modulo 3. PMID- 1518092 TI - Estimating the fraction of invariable codons with a capture-recapture method. AB - A codon-based approach to estimating the number of variable sites in a protein is presented. When first and second positions of codons are assumed to be replacement positions, a capture-recapture model can be used to estimate the number of variable codons from every pair of homologous and aligned sequences. The capture-recapture estimate is compared to a maximum likelihood estimate of the number of variable codons and to previous approaches that estimate the number of variable sites (not codons) in a sequence. Computer simulations are presented that show under which circumstances the capture-recapture estimate can be used to correct biases in distance matrices. Analysis of published sequences of two genes, calmodulin and serum albumin, shows that distance corrections that employ a capture-recapture estimate of the number of variable sites may be considerably different from corrections that assume that the number of variable sites is equal to the total number of positions in the sequence. PMID- 1518093 TI - Chaos game representation of coding regions of human globin genes and alcohol dehydrogenase genes of phylogenetically divergent species. AB - Chaos game representation (CGR) is a novel holistic approach that provides a visual image of a DNA sequence quite different from the traditional linear arrangement of nucleotides. Although it is known that CGR patterns depict base composition and sequentiality, the biological significance of the specific features of each pattern is not understood. To systematically examine these features, we have examined the coding sequences of 7 human globin genes and 29 relatively conserved alcohol dehydrogenase (Adh) genes from phylogenetically divergent species. The CGRs of human globin cDNAs were similar to one another and to the entire human globin gene complex. Interestingly, human globin CGRs were also strikingly similar to human Adh CGRs. Adh CGRs were similar for genes of the same or closely related species but were different for relatively conserved Adh genes from distantly related species. Dinucleotide frequencies may account for the self-similar pattern that is characteristic of vertebrate CGRs and the genome specific features of CGR patterns. Mutational frequencies of dinucleotides may vary among genome types. The special features of CG dinucleotides of vertebrates represent such an example. The CGR patterns examined thus far suggest that the evolution of a gene and its coding sequence should not be examined in isolation. Consideration should be given to genome-specific differential mutation rates for different dinucleotides or specific oligonucleotides. PMID- 1518094 TI - Delayed onset muscle soreness: mechanisms and management. AB - This review describes the phenomenon of delayed onset muscle soreness (DOMS), concentrating upon the types of muscle contraction most likely to produce DOMS and the theories underlying the physiological mechanisms of DOMS. Ways of attempting to reduce the effects of DOMS are also summarized, including the application of physical and pharmacological therapies to reduce the effects of DOMS and training for reduction or prevention of DOMS. PMID- 1518095 TI - The biomechanics of the triple jump: a review. AB - The purpose of this paper is to review the published opinions of coaches and the findings of scientists concerning the techniques used in the triple jump, and to identify promising avenues for future research on the subject. A model is developed to identify those factors that have a causal role in determining the official distance of a triple jump. This model is then used as a basis for the subsequent review. The review itself considers each of the biomechanical factors identified in the model, some additional factors reported in the literature, and selected characteristics of triple jumping techniques. It is concluded that research on triple jump techniques has been sparse and has had little impact on practice. Identification of the individual attributes that determine the optimum ratio of the phase distances for a given athlete, the loads to which the supporting legs are subjected and the control of balance during a triple jump are seen as challenging and potentially useful topics of future research. PMID- 1518096 TI - Group cohesion and starting status in successful and less successful elite volleyball teams. AB - The main purpose of this study was to examine the relationship between members' perceptions of group cohesion and starting status in elite volleyball teams. The results of the study revealed that the form of the cohesion-starting status relationship was moderated by the variable of success. The results for less successful teams revealed that differences did emerge between specific measures of cohesion endorsed by starters and non-starters. No such differences in cohesion emerged when the starters and non-starters on successful teams were compared. These results provide initial support for the suggestion that the most successful teams are the ones where the perceptions of cohesiveness by starters and non-starters are similar. A secondary purpose of the study was to determine whether those teams that were the most successful and similar in their members' perceptions of cohesiveness, were also the teams whose members have the most positive outcome expectancy. The results supported this prediction. PMID- 1518097 TI - Scientists 'build a better mouse' to trap biochemical secrets of radiation resistant cancer cells. PMID- 1518098 TI - How health care is; how it might be. PMID- 1518099 TI - From the Centers for Disease Control. Publicly funded HIV counseling and testing- United States, 1991. PMID- 1518100 TI - High-dose chemotherapy with autologous bone marrow transplantation for metastatic breast cancer. PMID- 1518101 TI - Specialists or generalists? The Medical Outcomes Study. PMID- 1518102 TI - Specialists or generalists? The Medical Outcomes Study. PMID- 1518103 TI - HIV infection and smoking behavior. PMID- 1518104 TI - HIV infection and smoking behavior. PMID- 1518105 TI - Autologous transfusion-transmitted Yersinia enterocolitica. PMID- 1518106 TI - Freon and hypertension. PMID- 1518107 TI - Intentional self-injection with HIV. PMID- 1518108 TI - Evaluation of bilirubin in a liver screening panel. PMID- 1518109 TI - Prognosis after first myocardial infarction. Comparison of Q-wave and non-Q-wave myocardial infarction in the Framingham Heart Study. AB - OBJECTIVE: To compare the short- and long-term prognosis following a first Q-wave or non-Q-wave myocardial infarction. DESIGN: Cohort study with a mean follow-up period of 5.1 +/- 4.9 years. SETTING: Population-based. PARTICIPANTS: Framingham (Mass) Heart Study subjects with an initial recognized myocardial infarction during a 17-year period were studied, including 227 men and 136 women with a mean age of 67.2 years. Seventy-seven percent of first infarctions were Q-wave infarctions and 23% were non-Q-wave infarctions. MAIN OUTCOME MEASURES: Reinfarction and death from coronary heart disease. RESULTS: During the follow-up period, subjects with non-Q-wave infarctions had a significantly higher rate of reinfarction than subjects in the Q-wave group (P = .02 for the entire follow up). The 10-year reinfarction rates were 44.8% vs 27.4%. When analyzed separately by age and sex, differences in reinfarction rates were only noted in men and in those under the age of 65 years. There were no differences in coronary heart disease death rates based on Q-wave status, even when examined separately by age and sex. Multivariate analysis revealed a 1.8-fold higher risk of reinfarction in the non-Q-wave group (95% confidence interval, 1.1 to 3.1), and also demonstrated that baseline hypertension was an independent risk factor for predicting reinfarction (relative risk, 1.8; 95% confidence interval, 1.1 to 3.2). There were no differences in the rates of sudden death or all-cause mortality following the two types of myocardial infarction. Additionally, subjects with a first Q wave infarction had a higher rate of subsequent congestive heart failure, while those with non-Q-wave infarctions had a significantly higher rate of coronary insufficiency (unstable angina with transient ST-T wave abnormalities). CONCLUSIONS: These results confirm and extend findings from prior studies that have identified patients with first non-Q-wave myocardial infarctions as potentially unstable, with greater subsequent morbidity and similar mortality to their counterparts with Q-wave infarctions. PMID- 1518110 TI - The comparative retention of National Health Service Corps and other rural physicians. Results of a 9-year follow-up study. AB - OBJECTIVE: To contrast the retention of physicians serving National Health Service Corps (NHSC) Scholarship Program obligations in rural settings to that of non-NHSC physicians working in the same or similar practices, and to identify promising retention-enhancing strategies. DESIGN: Cohort study. PARTICIPANTS: Four hundred twelve primary care physicians initially identified during an earlier study as working in a national stratified random sample of 178 externally subsidized rural clinics in 1981. Thirty-six percent were serving obligations to the NHSC, nearly all through the NHSC's Scholarship Program. The NHSC and non NHSC inception cohorts (those first coming to their 1981 [or "index"] practices from May 1979 through December 1981) were created from within the entire group for use in most analyses. INTERVENTION: In 1990, physicians were resurveyed to learn of their backgrounds, experiences in their index practices, and their subsequent career moves. RESULTS: By 1984 and in each year thereafter, fewer NHSC than non-NHSC physicians of the entire respondent cohort remained (1) in their index practices, (2) in their index communities, and (3) in practice in any rural county (P less than .001). In the inception cohort, fewer NHSC than non-NHSC physicians were retained within all three settings by the third year after their initial dates of employment (P less than or equal to .01). After 8 years of employment, group retention rates for NHSC and non-NHSC inception cohort physicians were 12% vs 39% in the index practice and 29% vs 52% in nonmetropolitan practice. Physicians in both NHSC and non-NHSC groups who left their index practices generally left rural practice altogether. CONCLUSIONS: When compared to non-NHSC physicians working in comparable rural settings, the retention of rural NHSC physicians is seen to be poor and only partially explained by fixed physician, practice, or community variables. Long-term retention of NHSC providers is now receiving much needed attention at the federal level. PMID- 1518111 TI - Improved cholesterol-related knowledge and behavior and plasma cholesterol levels in adults during the 1980s. AB - OBJECTIVES: To determine whether cholesterol-related knowledge and behavior and plasma cholesterol levels were stable until the inception of large-scale national interventions in the middle to late 1980s, whether they subsequently improved, and whether these levels varied by subgroups. DESIGN, SETTING, AND PARTICIPANTS: Data were collected from 4173 adults aged 25 through 74 years in the two control cities (San Luis Obispo and Modesto, Calif) of the Stanford Five-City Project. Five separate, community-based surveys were conducted in 1979-1980, 1981-1982, 1983-1984, 1985-1986, and 1989-1990. RESULTS: Cholesterol-related knowledge and behavior and plasma cholesterol levels improved (P = .0001) in both cities after the early 1980s. Those who were more educated, female, older, or nonsmokers had significantly higher knowledge and behavior scores, and those who were younger, more educated, or normotensive had significantly lower plasma cholesterol levels. CONCLUSION: Improvements in this population's cholesterol-related knowledge and behavior and plasma cholesterol levels began in 1985-1986, suggesting that the extensive cholesterol interventions that began in the middle 1980s in the United States created positive cholesterol-related changes at the community level. PMID- 1518112 TI - Reconciling the epidemiology, physiology, and molecular biology of colon cancer. PMID- 1518113 TI - Tuberculosis and HIV infection in sub-Saharan Africa. AB - OBJECTIVES: To review the epidemiologic, clinical, and pathological characteristics and the public health implications of human immunodeficiency virus (HIV)-associated tuberculosis in sub-Saharan Africa. DATA SOURCES: Published medical literature (English and French) and proceedings of international and African conferences on the acquired immunodeficiency syndrome (AIDS). STUDY SELECTION: Selection by the authors of articles most pertinent to HIV infection and tuberculosis in Africa and internationally. DATA EXTRACTION: Direct reporting of quantitative data (eg, HIV seroprevalence levels) and of qualitative descriptions and conclusions from selected literature. DATA SYNTHESIS: High rates (20% to 67%) of HIV infection in patients with tuberculosis have been reported from East, West, Central, and Southern Africa. An increase in tuberculosis cases has been reported at the same time as the emergence of AIDS in several countries. Autopsies in Abidjan, Ivory Coast (Cote d'Ivoire), have shown tuberculosis as the most frequent opportunistic infection in patients dying of AIDS. Clinical differences in patients with tuberculosis who were HIV-positive and HIV-negative are reviewed, the most important being a greatly increased mortality rate in HIV-associated disease. Access to HIV testing is required for firm diagnosis, for clinical care and counseling, and for public health surveillance. CONCLUSIONS: The epidemiology of tuberculosis has been profoundly influenced by the epidemic of HIV infection in sub-Saharan Africa. Greatly increased human and material resources are required for this neglected problem in international health. PMID- 1518114 TI - Can states take the lead in health care reform? PMID- 1518115 TI - Q-wave vs non-Q-wave myocardial infarction. An oversimplified dichotomy. PMID- 1518116 TI - The archives of Family medicine. Emphasizing primary care in the 1990s. PMID- 1518117 TI - Improving the supply of physicians in rural areas. PMID- 1518118 TI - [Antimicrobial activity of cefetamet against fresh clinical isolates of Branhamella catarrhalis]. AB - Against strains of Branhamella catarrhalis which were separated from various RTIs (respiratory tract infections) in 1991 antimicrobial activities (MICs) of cefetamet (CFMT) were determined, and the following conclusions were obtained. 1. The MIC80 of CFMT against B. catarrhalis was 0.39 microgram/ml, which was higher than that of cefixime (CFIX) by one dilution or twofold, but was lower than that of cefpodoxime (CPDX) by two dilutions or fourfold and that of cefotiam (CTM) by three dilutions or eightfold. 2. The fact that all of the 50 strains tested were beta-lactamase producers appeared to indicate that CFMT was stable against BRO-1 and BRO-2 beta-lactamases produced by B. catarrhalis. 3. Blood concentrations of the test drug, CFMT, and control drugs upon normal single doses were calculated using pharmacokinetic parameters. Lengths of time periods during which drug concentrations stayed above their MICs against B. catarrhalis obtained in this study were determined for CFMT, CFIX, CPDX and CTM. They were, respectively, 12 hours, 12 hours, 6 hours, and 2 hours, thus CFMT appeared to remain above MIC for sufficiently long time for the treatment of RTIs which are affected by B. catarrhalis directly or indirectly. PMID- 1518119 TI - [Effect of cefclidin and E1077, new cephalosporins, on the alcohol-metabolizing system in rats]. AB - Administration of latamoxef and cefoperazone, reported to act like disulfiram in humans, caused a depression of mitochondrial low Km aldehyde dehydrogenase (low Km ALDH) activity in rats. In addition, a marked increase of blood acetaldehyde concentration was observed when rats were given alcohol orally at 18 hours after administration of these cephalosporins. However, mitochondrial low Km ALDH activity and blood acetaldehyde level were not altered by repeated administration of 300 mg and 1,000 mg of cefclidin (CFCL, E1040) or E1077 per kg. From these results, it was concluded that neither CFCLn or E1077 affected the alcohol metabolizing-system. PMID- 1518120 TI - [Laboratory and clinical studies on panipenem/betamipron in the field of pediatrics]. AB - Laboratory and clinical studies on panipenem/betamipron (PAPM/BP), a new carbapenem antibiotic, were carried out in the field of pediatrics and the following results were obtained. 1. The antibacterial activities of panipenam (PAPM) against clinically isolated organisms in our department were high overall. 2. After 30 minutes intravenous infusion of PAPM/BP at a dose of 10 mg/10 mg/kg in 1 and of 20 mg/20 mg/kg in 2 children, peak plasma levels of PAPM ranged from 33.21 to 75.66 micrograms/ml at the end of the infusion. The half-lives were 0.81 to 0.93 hours. The cumulative urinary recovery rates in the first 6 hours after the start of drip infusion ranged from 10.7 to 40.4%. 3. PAPM/BP was administered to 16 pediatric patients with various infections. The clinical and bacteriological efficacy rates were both 100%. 4. No side effects were observed. Abnormal laboratory test results were also mild; slight elevation of GOT, GOT/GPT and eosinophylia in 1 each and thrombocytosis in 2. PMID- 1518121 TI - [Studies on panipenem/betamipron in the field of pediatrics]. AB - Pharmacokinetic and clinical studies in pediatrics were performed on panipenem/betamipron (PAPM/BP), a combined drug of a carbapenem antibiotic (panipenem) and organic ion inhibitor (betamipron) at a weight ratio of 1:1. 1. Plasma levels and urinary excretion were studied when PAPM/BP, at 10 mg/10 mg/kg (4 cases) or 20 mg/20 mg/kg (5 cases), was administered using intravenous drip infusion in 30 minutes to 9 children (4-14 years old). The plasma PAPM level at the end of drip infusion was 30.75 +/- 4.98 micrograms/ml in the cases administered with 10 mg/10 mg/kg and 68.72 +/- 5.73 micrograms/ml in the cases administered with 20 mg/20 mg/kg. Drug concentrations then gradually decreased with half-lives of 1.08 +/- 0.09 hours and 0.98 +/- 0.02 hour, and reached 0.39 +/- 0.14 micrograms/ml and 0.62 +/- 0.06 micrograms/ml, respectively, after 5.5 hours. Plasma BP levels at the end of drip infusion was 18.93 +/- 3.75 micrograms/ml in the cases administered 10 mg/10 mg/kg and 37.09 +/- 2.68 micrograms/ml in the cases administered 20 mg/kg, and half-lives were 0.55 +/- 0.07 hour and 0.61 +/- 0.03 hour, respectively; the plasma BP level could not be determined in any cases after 5.5 hours. Mean urinary recovery rates of PAPM in the first 6 hours after the start of intravenous drip infusion were 33.0 +/- 6.1% in the cases administered 10 mg/10 mg/kg and 21.8 +/- 2.3% in the cases administered 20 mg/20 mg/kg and those of BP were 77.0 +/- 2.4% and 76.6 +/- 7.3%, respectively. 2. When PAPM/BP, was administered at 31.3 mg/31.3 mg/kg thought by intravenous drip infusion in 30 minutes to 1 case of purulent meningitis, PAPM levels were 0.76 micrograms/ml at the end of drip infusion but varied between 0.80 to 1.97 micrograms/ml 30 minutes after the end of drip infusion during 8 days of treatment. 3. PAPM/BP was administered to 43 cases, 47 diseases of bacterial infections in the domain of pediatrics to study its clinical efficacy, bacteriological efficacy and adverse reactions. Single doses were 5.2mg/5.2mg to 31.3 mg/31.3 mg/kg; frequencies of administration were 3 to 4 times a day, and durations of administration were 3 1/3 to 11 days; and total dosages ranged between 1.125 g/1.125 g and 11.0 g/11.0 g.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1518122 TI - [Evaluation of panipenem/betamipron in pediatric field]. AB - Panipenem/betamipron (PAPM/BP), a mixture of a newly synthesized carbapenem antibiotic panipenem (PAPM) and N-benzoyl-beta-alanine, betamipron (BP), was evaluated for pharmacokinetics, in vivo and in vitro antimicrobial effect, and clinical efficacy in pediatric patients. Intravenous drip infusion of either 10 mg/10 mg/kg or 20 mg/20 mg/kg of PAPM/BP for 30 minutes resulted in maximum plasma concentrations of 36.6 micrograms/ml and 92.5 micrograms/ml, half lives (T 1/2 beta) of 1.17 hours and 0.88 hours, and urinary excretion until 6 hours of 29% and 17.7%, respectively. Antibacterial activities of PAPM against Gram positive cocci and Gram-negative rods isolated from pediatric patients were equal to or slightly stronger than those of imipenem, ceftazidime, cefoperazone, and piperacillin. Clinical effects of PAPM/BP evaluated in 17 patients were as follows; excellent in 8 cases, good in 8 cases, and fair in 1 case. The overall efficacy rate was 94.1%. Elevations of GOT and/or GPT were observed in 2 patients and transient eosinophilia was observed in 1 patient. PMID- 1518123 TI - [Clinical studies on panipenem/betamipron in pediatric field]. AB - We have carried out clinical studies on panipenem/betamipron (PAPM/BP, CS-976). The results are summarized as follows. Treatment with PAPM/BP was made in 21 cases of pediatric bacterial infections including 2 cases of tonsillitis, 15 cases of pneumonia and 1 case each of bronchitis, scarlet fever, urinary tract infection and otitis media. Results obtained were excellent in 15 cases, good in 6 cases. No significant side effects due to the drug were observed in any cases. PMID- 1518124 TI - [Studies on efficacy and safety of panipenem/betamipron against infections in pediatrics and on its movement to cerebrospinal fluid including cases of penicillin-resistant Streptococcus pneumoniae meningitis]. AB - The efficacy and the safety of panipenem/betamipron (PAPM/BP), a new carbapenem antibiotic against infections in pediatrics were studied. The obtain results are summarized as follows. 1. The transfer of PAPM/BP to cerebrospinal fluid (CSF) was studied in 2 cases of purulent meningitis. The PAPM/BP levels in CSF in a dose 26.1 mg/kg peaked at 3.21 micrograms/ml on sampling 30 minutes after administration, followed by decreasing gradually with the improvement in clinical symptoms and came to 0.86 micrograms/ml on the 12th day (30 minutes after administration). 2. PAPM/BP at dose levels of 50 mg/kg to 69 mg/kg a day (daily doses of 104 mg/kg, 175 mg/kg 4 times a day for 2 cases of purulent meningitis) was administered by intravenous drip infusion 3 times daily for 4 to 15 days to 2 cases of purulent meningitis (including 1 case of penicillin-resistant Streptococcus penumoniae meningitis), 3 cases of pneumonia, 2 cases of phlegmon, 2 cases of periproctal abscess and 2 cases of urinary tract infections for a total of 11 cases. As results, all the cases showed good responses including 5 excellent and 6 good responses. Bacteriological efficacies in all of the 9 eligible cases were assessed as "eradicated". 3. As for the safety, an increase in the platelet count and slight evaluation of GOT and GPT were seen in 1 case as abnormal changes in the laboratory findings, although no side-effect was observed. 4. The results above show that PAPM/BP is useful for the treatment of general infections in pediatrics and that a daily dose of about 60 mg/kg given in 3 divided doses in effective enough.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1518125 TI - [Clinical evaluation of panipenem/betamipron in pediatrics]. AB - Studies were carried out on the clinical efficacy of panipenem/betamipron (PAPM/BP) against bacterial infections. The results are summarized as follows: 1. PAPM/BP were administered to total 21 patients (7 cases of pneumonia, 1 case of bronchitis, 3 cases of cellulitis, 2 cases of purulent lymphadenitis, 2 cases of otitis media, 1 case of purulent parotitis, 1 case of sinusitis, 1 case of mastoiditis, 2 cases of urinary tract infection and 1 case of purulent meningitis) by drip intravenous injection. 2. Clinical responses of PAPM/BP were excellent in 12 cases, good in 7, poor in 1 and unknown in 1 case. The overall efficacy rate was 95.0%. 3. Concentration of PAPM in cerebrospinal fluid after 1 hour drip intravenous administration in 1 case of purulent meningitis were 6.84 micrograms/ml at the acute stage and 3.28 micrograms/ml at the recovering stage. 4. Neither side effects nor abnormal laboratory findings were observed except 1 case of increase of thrombocytosis out of 19 cases. 5. From the results, PAPM/BP was determined to be an efficacious and safe drug for the therapy of pediatric infection. PMID- 1518126 TI - [Clinical studies on panipenem/betamipron in pediatrics]. AB - Panipenem/betamipron (PAPM/BP) was given by 30 minutes drip infusion to 15 children with acute bacterial infections including 11 with acute pneumonia, 2 each with staphylococcal scalded skin syndrome and urinary tract infections. Good to excellent clinical responses were obtained in all of the 15 patients and bacterial eradications were obtained for all 12 strains identified in these cases. Urticaria considered to be drug related was observed in 1 patient. Slight elevations of GOT and GPT and eosinophilia were observed in 1 case each. From the above clinical results, it appears that PAPM/BP is a useful antibiotic for treatment of pediatric patients with various bacterial infections. PMID- 1518127 TI - [Clinical studies of panipenem/betamipron in pediatrics]. AB - We conducted clinical studies on panipenem/betamipron (PAPM/BP), a newly developed parenteral carbapenem antibiotic, for its clinical application in the field of pediatrics. 1. A clinical study was performed on 13 children with infections, including 6 with acute bronchopneumonia, 1 each with acute pharyngitis, acute bronchitis, sepsis, staphylococcal scalded skin syndrome, urinary tract infection, subcutaneous abscess and furuncle. PAPM/BP was administered by intravenous drip infusion. Doses varied from 12 to 27 mg/kg body weight were given t.i.d. or q.i.d. Lengths of treatment ranged from 4 to 25 days. Clinical efficacies were excellent in 3 and good in 9 cases, with an efficacy rate of 92%. 2. No adverse reactions were observed. In laboratory tests, elevations of GOT, GPT and urobilinogen were observed in 3 cases. It was concluded that PAPM/BP was a promising drug for the treatment of bacterial infections in children. PMID- 1518128 TI - [Pharmacokinetics and clinical studies of panipenem/betamipron in the pediatric field]. AB - Panipenem/betamipron (PAPM/BP) is a mixture of panipenem (PAPM), carbapenem antibiotic, and betamipron (BP), N-benzoyl-beta-alanine. The adverse reaction to PAPM of the kidney is reduced by the addition of BP to PAPM which inhibits the anion transport in the kidney tubules. We studied the pharmacokinetics and the clinical efficacies of PAPM/BP in children and we evaluated the antibacterial activities of PAPM by determining MIC values of PAPM in vitro against organisms isolated in our children's hospital from January to December, 1990. 1. Pharmacokinetics 10 mg/kg of PAPM/BP (10 mg PAPM/10 mg BP) was administered intravenously by drip infusion to 7 children. The mean blood concentration of PAPM was 14.8 micrograms/ml at the peak, and the mean half life was 0.9 hours in blood. PAPM was not detected in blood 3 hours after the time when the peak values were attained. 2. Clinical studies 10 mg/kg of PAPM/BP was administered intravenously 3 times a day to 18 cases including 15 of respiratory infections, 2 of otitis media and 1 of sepsis. The clinical efficacies of PAPM/BP were excellent or good in 17 out of the 18 cases. All causative organisms isolated in 5 cases, Methicillin-sensitive Staphylococcus aureus (MSSA) (1 case), Streptococcus pneumoniae (1), Haemophilus influenzae (2) and Branhamella catarrhalis (1) were eradicated in a few days upon the administrations of PAPM/BP. No adverse reactions due to PAPM/BP were observed, but a slight elevation of platelet counts in blood was observed in 1 case, which was normalized soon after the end of the treatment. 3. Antibacterial activities in vitro(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1518129 TI - [Differentiation and phenotype of blood cells]. PMID- 1518130 TI - [Immunoglobulin and T cell receptor gene rearrangements during lymphocyte differentiation]. PMID- 1518131 TI - [Mixed lineage leukemia--definition and classification]. PMID- 1518132 TI - [Chromosomal aberrations in hematologic neoplasia]. PMID- 1518133 TI - [Recent advances in investigations for hematological malignancies]. PMID- 1518134 TI - [Diagnosis and classification of leukemia]. AB - Modern diagnosis and classification of leukemia are reviewed. The FAB (French, American, British) classification, introduced in the late 1970s has been the basis for most studies to date. During the 15 years since then, new categories such as M7 and M0 were added to the classification. The MIC proposal (morphology, immunology, cytogenetics) has been an important development which emerged from the knowledge about chromosomal changes and immunophenotyping. Improvement in diagnosis and classification will emerge from studies employing all the above techniques, including DNA analysis, in the 1990s. PMID- 1518135 TI - [A new system of diagnosis and classification--malignant lymphoma]. AB - Malignant lymphoma is usually divided into Hodgkin's disease (HD) and non Hodgkin's lymphoma (NHL) according to biological characteristics. Malignant lymphoma in Japan has such the characteristics as few incidence of HD, which is usually favorable in prognosis, and high incidence of NHLs, which have further distinctive features of less incidence of favorable follicular B cell lymphoma and of higher incidence of unfavorable diffuse T cell lymphoma including adult T cell leukemia/lymphoma (ATLL) in comparison with those in western countries. As a recent trend of progress in lymphoma diagnosis an introduction of immunological and molecular biological techniques has given an impact to the previous classification of malignant lymphoma based mainly on morphological criteria. Nowadays, the classification of pathologic type in HD seems to be settled in Rye classification. On the other hand in NHL the LSG classification has been well fixed in Japan and Working Formulation originated in USA has been well used internationally after a historical confusion. In this article a present state of working classification in malignant lymphoma is briefly described and discussed. PMID- 1518136 TI - [Usefulness of monoclonal antibodies for immunophenotyping in leukemia]. AB - Clinically useful monoclonal antibodies, applied for immunophenotyping of leukemias, are reviewed. With a combination of 15 antibodies, including CD2, CD3, CD4, CD5, CD7, and CD8 for T cell marker analysis, CD10, CD19, CD20, surface immunoglobulins, and cytoplasmic mu chain for B cell marker analysis, CD13 and CD33 for myeloid marker analysis, and HLA-DR and CD25 for other marker analysis, acute lymphoblastic leukemias of T cell type, cALL type, pre-B cell type and B cell type, acute myeloid leukemias, acute unclassified leukemias and adult T cell leukemias could be clearly diagnosed by immunophenotyping of cell membrane molecules. By using additional CD11b, CD14, and CD15 monoclonal antibodies, subclassification of acute myeloid leukemia was partially possible. PMID- 1518137 TI - [Immunologic phenotype of malignant lymphoma]. AB - Recent advances in clinical research on surface marker analysis of malignant lymphoma cells are reviewed. Malignant lymphoma can be classified into T-cell malignancy or B-cell malignancy, using flow cytometry or immunohistochemical analysis. Based on recent results of immunophenotypic analysis and clinical data, a new clinicopathologic classification of lymphoid malignancy is proposed. T-cell malignancy bearing T-cell receptor of gamma delta-type is discussed. Other recent topics on malignant lymphoma, such as B-cell lymphoma of the pleural cavity developing from long-standing pyothorax, mediastinal large-B-cell lymphoma with sclerosis, HIV-related B-cell lymphoma, and EB-virus genome carrying B-cell lymphoma in ATL are also discussed. PMID- 1518138 TI - [Immunophenotypic analysis in acute leukemia]. AB - Acute leukemias have been classified on French-American-British (FAB) criteria depending on the morphocytochemical features of blasts. Immunophenotyping and clonal rearrangement analysis of lineage-associated genes can decide a frozen stage of the hematopoietic differentiation process in blasts from acute leukemias. B-lineage acute lymphoblastic leukemia (ALL) and T-lineage ALL are systematically classified according to the sequential expression of differentiation-associated antigens. In acute myelogenous leukemia (AML), several new entities are proposed: AML-M0 is an AML without cytologic maturation, in which the myeloid commitment should be demonstrated by myeloperoxidase-positive microgranule on immunohistochemical staining or electron-microscopy, or by positive reaction for CD13 or CD33 antigens. CD7-positive AML is considered to be one of immature subtypes of AML, rather than hybrid leukemia. Thus, immunological studies on blasts enable us to discriminate a subgroup of leukemias, which will perhaps contribute to the improvement of treatment approach. PMID- 1518139 TI - [Immunophenotype of chronic lymphocytic leukemia and prolymphocytic leukemia]. AB - The immunophenotype of chronic lymphocytic leukemia (CLL) and prolymphocytic leukemia (PLL) is described, mainly according to the FAB classification. CLL and related diseases have been recognized as highly variable diseases and their classification is still confusing. Is there true T-CLL? How should we deal with non-T, non-B-CLL such as NK-GLL? What about the patient with borderline manifestations? Is the concept "MLUS" appropriate? Further examination and more detailed analysis is required in order to clarify the disease entity of CLL and related disorders. PMID- 1518140 TI - [Large granular lymphocytic leukemia]. AB - We investigated the surface markers, cell-function, clonality, and the association of IL-2 receptors and a second messenger of src family of tyrosine kinase p56lck in IL-2 signal transduction of the leukemic cells of 12 patients with large granular lymphocytic leukemia (LGL leukemia). The leukemic cells of 5 patients were CD3+ and 5 of them were CD3-. In three patients with CD3- leukemia examined, one showed karyotype abnormality of 46, XY, -10, +mar and the delta gene of TCR was rearranged in one patient. The TCR of the leukemic cells of a patient MH with CD3+, CD4 and CD8 (double positive marker: DP) recognised rabbit IgG presented by macrophages. The recognition was class II restricted. We examined the expression pattern of CD8 subunits and found that DP leukemic cells commonly expressed CD8 alpha+ beta-. These results suggested that DP leukemic cells were CD4+ T cells and expressed CD8 alpha secondarily. The p75 IL-2 receptors were detected, however, the modulation of p56lck in the process of IL-2 signal transduction were not found out. There was no association between p75 and p56lck when leukemic LGL cells proliferated on stimulation with IL-2. PMID- 1518141 TI - [Immunophenotyping analysis of acute undifferentiated leukemia]. AB - The diagnosis of acute undifferentiated leukemia (AUL) is made when the leukemic cells do not have cytologic or cytochemical features of myeloid cells, and do not express myeloid antigens (CD13, CD14, CD33, CD41 etc.) or lymphoid antigens (CD2, CD3, CD19, CD20, Sm Ig etc.). Most of these cells are reported to be positive for CD7, CD34, TdT and HLA-DR, either alone or in combination. Cell lineage can be suspected in most AUL cells by genotypic analysis, phenotypic analysis after culturing with TPA, or peroxidase activity by ultrastructural or immunohistochemical analysis, which indicates the heterogeneity of AUL. The patients with AUL appear to have a poor prognosis with conventional chemotherapy. PMID- 1518142 TI - [Bi-phenotypic leukemia and hybrid leukemia]. AB - Phenotypes of leukemic cells can be determined through dual staining with pairs of FITC-labeled and PE-labeled monoclonal antibodies using a laser flow cytometer. Hybrid acute leukemia (HAL) was diagnosed when leukemic cells expressed 2 or more lymphoid markers and at least one myeloid maker simultaneously. Based on this criteria, forty out of 111 cases with untreated acute leukemia were diagnosed as HAL, 16 of 41 (39%) patients with acute lymphoblastic leukemia and 15 of 70 (21%) patients with acute non-lymphocytic leukemia were diagnosed as having HAL. We classified these HAL cells into 4 types by the following items. Type I; leukemic cells expressed only CD33 and 2 or more B-cell antigens, type II; only CD33 and 2 or more T-cell antigens, type III; CD13 and/or CD33 and 2 or more B-cell antigens, and type IV; CD13 and/or CD33 and 2 or more T-cell antigens. There were 7 type I cases and 16 type III cases. The leukemic cells of these two types were thought to be ALL cells expressing one or several myeloid lineage-associated antigens. There were 4 type II cases and 10 type IV cases. Type II and IV were regarded as lymphoid-lineage associated antigens positive AMLs. At least in adults, the expression of myeloid-associated antigens of ALL cells seems to identify a high risk group of ALL patients with a poorer response to standard ALL therapy. PMID- 1518143 TI - [Immunogenotypes and surface marker analysis in Ph1 positive chronic myelogenous leukemia in the blastic crisis]. AB - Immunophenotypic and immunogenotypic changes in 23 patients with Ph positive chronic myelogenous leukemia in blast crisis were determined using a panel of monoclonal antibodies and gene probes. According to the immunophenotypes, 9 patients were considered to be in lymphoid blast crisis, including 7 patients with lymphoblastic crisis and 2 patients with lymphoid/myeloid mixed blast crisis. Leukemia cells from the remaining 14 patients showed myeloid phenotypes and 10 of these had platelet-associated antigens. Rearrangement of the immunoglobulin (Ig) gene was observed in all the 9 patients with lymphoid blast crisis, and Ig gene rearrangement was associated with the expression of CD19 antigen. Two patients with myeloid blast crisis showed rearrangements of T-cell receptor gene, but, dissociation between phenotypes and genotypes was not frequently observed in patients with blast crisis. PMID- 1518144 TI - [Review: progress of cytogenetics in hematopoietic malignancies]. AB - In 1960, Nowell and Hungerford found, for the first time, a minute chromosome at the metaphase in chronic myelocytic leukemia (CML) cells, which was called Philadelphia chromosome (9; 22 translocation) later. Ph1 chromosome was considered to be specific for the disease and was frequently used as an important marker for the definite diagnosis. In 1970s banding techniques revealed some other specific chromosome abnormalities, like 8; 14, 8; 21, and 15; 17 translocations, for acute leukemias. In 1980s, molecular-biology techniques were applied in the fields of leukemia research. As a result, many break point cluster regions were discovered in relation to the immunoglobulin chain genes and T cell receptor genes (Table 2). In this review, the specificity of chromosome abnormalities as well as genetic changes in types of leukemia is discussed. PMID- 1518145 TI - [Ph1-positive leukemia: cytogenetic outline and prognosis]. AB - Ph1-positive leukemias consist of acute leukemia (Ph1 AL) and CML. Cytogenetically, Ph1 AL is often associated with +6, -7, +8, +21, or +Ph1. CML is predominantly accompanied by +Ph1, +8, i (17q), +19 in myeloid crisis and +Ph1, +8, +21 in lymphoid crisis. Thus, i(17q) seems specific for myeloid crisis of CML. Ph1 constricts ABL/BCR within M-BCR in CML and in one half of the adult Ph1 AL. BCR breaks upstream to M-BCR in the other half of adult AL and in most of childhood AL. However, the breakpoint does not affect clinical and hematological features in AL. Consequently, there seems to be two types of Ph1 leukemia; one is AL representing m-BCR rearrangement and the other is CML and Ph1 AL showing M-BCR rearrangement. PMID- 1518146 TI - [Correlation between karyotype and prognosis in adult lymphocytic leukemia]. AB - Correlation between karyotype and prognosis in adults with lymphocytic leukemia are reviewed. Concerning acute lymphoblastic leukemia (ALL), patients with normal karyotype or with hyperdiploidy (greater than 50 chromosomes) show good prognosis. On the other hand, patients with structural abnormalities, such as t(8;14), t(4;11), t(11;14) or with hyperdiploidy (47 to 50 chromosomes), show poor prognosis. Above findings indicate that karyotype is a significant prognostic factor in adults as well as in children with ALL. Karyotype must be considered in designing clinical trials to improve the prognosis in patients with lymphocytic leukemia, especially in ALL. PMID- 1518147 TI - [Chromosome abnormalities and prognosis in childhood acute leukemia]. AB - The chromosomal classification system of childhood acute leukemia according to ploidy or structural chromosomal changes of leukemia cells is clinically useful for the prediction of the treatment outcome. While patients with hyperdiploid (greater than 50 chromosomes) ALL enjoy the best prognosis, those with hypodiploid or pseudodiploid ALL are expected to have unfavorable clinical outcome. Among various translocations or deletions in ALL, t(4;11), t(9;22) and t(8;14) predict the worst clinical outcome. AML patients with t(8;21) or inv (16) have better 50% survival than those with other chromosome changes or normal diploidy. Chromosome analysis of leukemia cells should be included in the diagnostic workup of childhood acute leukemia. PMID- 1518148 TI - [Chromosome abnormalities and prognosis in non-Hodgkin's lymphoma]. AB - Clonal chromosome abnormalities are found in most patients with non-Hodgkin's lymphoma. The role of the chromosome abnormalities in predicting the prognosis of lymphoma patients has not been fully clarified, because of different histological classifications being used in different areas and the complexity of the chromosome abnormalities often found in lymphoma. Recent studies have shown distinct correlation of rather rare abnormalities with specific histologic and immunologic phenotypes and prognoses. Many chromosome abnormalities seem to specifically correlate with these parameters of non-Hodgkin's lymphomas, as seen in leukemias. The chromosome data also seem to support the histological observations that some lymphomas may show uneven geographical distributions. PMID- 1518149 TI - [Applications of FISH to chromosome analysis in hematological malignancies]. AB - In situ hybridization provides a direct method to localize DNA sequences on metaphase chromosomes. Initially, nucleic acid probes were labeled isotopically and detected by autoradiography. Recently, fluorescent in situ hybridization (FISH) have been developed. FISH has resolved several problems, such as radiolysis of probes, long exposure times, high background noise, and unclear localization of silver-grains visualized by autoradiography. In addition, FISH allows us to study numerical and structural chromosome aberrations using chromosome-specific DNA probes, not only in metaphase chromosome, but also in interphase nuclei. Therefore, FISH can be applied to a broad spectrum of biological and clinical problems in hematological malignancies. PMID- 1518150 TI - [Immune gene rearrangement as markers of hematological malignancies]. AB - Molecular genetical analysis using Ig and TCR genes has been applied for hematological malignancies. In acute leukemias, this method is used to clarify the cellular lineage, and in malignant lymphomas to detect the monoclonal component. In this article, we describe the mechanism of immune gene rearrangement and the present status and future directions of immunogenetic analysis of leukemias and lymphomas. PMID- 1518151 TI - [Phenotypic and genotypic analysis of acute leukemia--current status of lineage specific classification]. AB - More detailed identification and understanding of the heterogeneity of leukemias using a broad panel of markers seems to be essential for the successful design of more sophisticated and effective treatments. Based on the FAB system, immunological phenotypes using a panel of monoclonal antibodies, and rearrangements of immunoglobulin and T-cell receptor genes, acute leukemia can be divided into six subtypes such as B-lineage, T-lineage, AML, NK-lineage, AUL and mixed lineage leukemia. The definition of B-lineage and T-lineage cells, a new classification for mixed lineage leukemia, incidence of dual rearrangements and their clinical significance are discussed. PMID- 1518152 TI - [PCR analysis of T cell antigen receptor genes for human lymphoid malignancies]. AB - T-cell receptor genes encode proteins related to their specific recognition structures. As is true for immunoglobulins, T-cell receptor genes consist of separate germ line segments that encode the variable and constant regions of the chain. The variable region genes are assembled from two or three separate germ line segments that somatically rearrange during differentiation. The diversity in the variable region of T-cell receptors results from germ line diversity of V, (D), and J sequences, combinatorial joining of the segments, junctional diversity leading to codon changes at the end of gene segments, N-region diversity arising from addition of template independent nucleotides at junction. Each T-cell clone has its own unique structure of the variable region, and in T-cell malignancies, this variable region is retained after malignant transformation. This enables the nucleotide sequences of the variable region genes to be used as a molecular marker for the malignant clone. By amplification of these sequences of variable genes, it is now possible to study the pathological features of the leukemic clones in vivo, as well as to follow the patients for minimal residual disease. PMID- 1518153 TI - [Chromosomal translocations involving immunoglobulin or T-cell receptor genes in lymphoid malignancy]. AB - Tumor-specific chromosomal translocations in lymphoid malignancy frequently involve the fusion of immunoglobulin (Ig) or T-cell receptor (TCR) gene loci with oncogenes, thereby activating the latter to contribute to the malignant phenotype. The preponderance of chromosomal translocations involving Ig or TCR genes suggests that the enzymatic machinery, the lymphocyte recombinase, is used in the formation of abnormal chromosomes. However, the role of ectopic recombination signals for recombinase in chromosomal translocations has been controversial. In this paper, molecular studies of genes adjacent to the breakpoints of these chromosomal translocation are reviewed, and the mechanism of chromosomal translocation and clinical characteristics of the tumor with specific chromosomal translocation are discussed. PMID- 1518154 TI - [Activation of protooncogenes by point mutations in hematological malignancies]. AB - The activation of protooncogenes (ras, fms and myc genes) by point mutations in hematological malignancies are described in this review. Ras mutations are found in a variety of human malignancies at codon 12, 13, and 61. Generally, N-ras mutations are frequent in hematological malignancies. Fms mutation at codon 301 and 969, which are seen in 10 to 20% cases of AML and MDS, increase tyrosine kinase activity of the fms products. Ras and fms mutations are postulated to influence leukemogenesis at rather early stages. Burkitt lymphomas are characterized by specific chromosomal translocations between c-myc gene and one of the immunoglobulin genes. Furthermore, mutations in the 3' border of the exon 1 of c-myc are frequent, and may play an additional role in pathogenesis of Burkitt lymphoma. PMID- 1518155 TI - [Activation of oncogenes by chromosomal translocation in hematopoietic tumors]. AB - Specific chromosomal translocations are one of the cytogenetic characteristics of hematopoietic malignancies. The application of molecular biological techniques has led to important insight into the molecular consequences, accompanied by the chromosomal translocations. Specific oncogenes and related genes activated by the translocations have been identified at the translocation breakpoints. Translocated oncogenes are deregulated by their juxtaposition to enhancers of Ig or TCR genes, resulting in their overexpressions in some lymphoid tumors. Alternatively, they are activated by gene fusion, resulting in a chimeric oncoprotein, as seen in Ph1-positive leukemia. The molecular consequences by chromosomal translocation in hematopoietic malignancies is focused here. PMID- 1518156 TI - [Abnormalities of the retinoblastoma susceptibility gene (RB) in hematologic malignancies]. AB - The retinoblastoma susceptibility gene (RB) is expressed in all lineages of normal hematopoietic cells and plays an important role in controlling cell cycle progression at G1/S. Abnormalities of the RB gene may, therefore, predispose to the development of hematologic malignancies. DNA rearrangement was reported to be present in 1.5-12.1% of cases with primary leukemias and the absence of the RB gene product was also observed in 6.3-23.2%. The abnormalities were frequently observed in blastic crisis of CML, especially of the megakaryoblastic phenotype, AML with monocytic differentiation and Ph1-positive leukemias. These results indicate that abnormalities of RB are relatively common in hematologic malignancies and loss of RB function may contribute to the altered growth of these cells. PMID- 1518157 TI - [Mutations of the p53 gene in hematologic neoplasms]. AB - The p53 gene encodes a nuclear phosphoprotein and is now considered as a tumor suppressor gene. Mutations of the p53 gene have frequently been observed in several types of solid tumors and are believed to be implicated in the development of these tumors. Recent studies have shown that the p53 gene is altered in chronic myelogenous leukemia (CML) in blast crisis. In CML, alterations of the p53 gene may play an important role in the development of blast crisis. More recently, p53 mutations have been reported in other types of hematologic neoplasms, such as acute leukemia, adult T-cell leukemia, and malignant lymphoma. These observations suggest that inactivation of the p53 gene is involved in the tumorigenesis of various types of hematologic neoplasms. PMID- 1518158 TI - [DCC gene and leukemia]. AB - The deleted in colorectal carcinomas (DCC) gene, located in human chromosome band 18q21, was identified as a potential tumor suppressor gene by Fearon et al. in 1990. The DCC gene encodes a protein which is highly similar to neural cell adhesion molecules and other related cell surface glycoproteins. In colorectal carcinoma, the expression of the DCC gene is reduced or absent in 88% of cases. We examined the expression of the DCC gene using reverse transcriptase-polymerase chain reaction (RT-PCR) analysis. Its expression was reduced or absent in some leukemias. Our findings suggest the possibility that this gene may play a role in leukemogenesis. PMID- 1518159 TI - [Overexpression of PRAD1 gene in B-cell malignancy with t(11;14)(q13;q32) translocation]. AB - PRAD1 (parathyroid adenoma 1) gene at chromosome 11q13 has been cloned from parathyroid adenomas as a putative oncogene, activated by translocation with the parathyroid hormone gene. 4.5 kb and 1.7 kb mRNA are transcribed and both have the same open reading frame of 885 bp encoding 34 kd protein of a cyclin gene family, cyclin D1. Recently, overexpression of PRAD1 gene has been reported to be correlated closely with the rearrangement of bcl-1 locus, particularly in centrocytic lymphoma. In our study, overexpression of PRAD1 gene was shown in five B cell lines with t(11;14)(q13;q32) including one centrocytic lymphoma line and 4 myeloma lines, when compared with other hematopoietic cell lines without translocation. One of the cell lines, SP-49, demonstrated a truncated mRNA of 3.4 kb, in addition to 1.7 kb of normal size. Southern blot analysis demonstrated a rearrangement with PRAD1 cDNA probe, suggesting that the gene is altered in this particular cell line. By cloning analysis, we confirmed that 1.8 kb deletion in 3' region of PRAD1 gene eliminating the destabilizing signal of PRAD1 mRNA, gave rise to the aberrant mRNA of 3.4 kb. These findings suggest that PRAD1 gene is most likely the candidate oncogene for bcl-1 activated by t(11; 14)(q13;q32) translocation. The gene alteration found in one cell line, SP-49, might also play an important role for deregulation of the gene. PMID- 1518160 TI - [Structure and function of oligosaccharide chains of the envelope glycoprotein gp120 of human immunodeficiency virus type 1]. AB - The surface of the human immunodeficiency virus (HIV-1), a causative agent for acquired immunodeficiency syndrome (AIDS), is covered with the major envelope glycoprotein gp120, of which the carbohydrate moiety accounted for 50% of the molecular mass. There is evidence that glycosylation of gp120 is prerequisite to the various stages of HIV infection. The oligosaccharide structures of gp120 have been determined using recombinant gp120 of HIV-1 (IIIB) produced in chinese hamster ovary cells and virus-derived gp120 isolated from H9 lymphocytes chronically infected with HIV-1 (IIIB). Three oligosaccharides have been suggested to be involved in the HIV-infection process. Occurrence of infection process which is independent of CD4 recognition and mediated by gp120 oligosaccharides, mannose-binding protein, and complement system has been suggested. PMID- 1518161 TI - [Recent advances in EDRF research]. AB - We have developed a new bioassay system for endothelium-derived relaxing factor (EDRF), using endothelial cells in culture. Bovine pulmonary arterial endothelial cells (BPAE) were grown on microcarrier beads and superfused in a cell column. The effluent was applied to bioassay tissues and biological and the chemical characters of EDRF were examined and compared with those of nitric oxide (NO). EDRF was vascular selective and negatively charged, whereas NO was a general relaxant and not charged. The hypothesis that EDRF is identical to NO is discussed. We also examined the interaction of some EDRF agonists with endothelial cells and biological characteristics of the agonists were discussed. PMID- 1518163 TI - Three-dimensional computed tomography image of small pulmonary lesions. AB - To evaluate diagnostic imaging of small lesions in the peripheral lung, three dimensional (3D) reconstruction CT images were used to study 36 cases (including which had been 19 resected) of pulmonary nodules less than 3 cm in diameter. Rapid scanning was employed in 17 cases and helical scanning (in which the X-ray tube rotates continuously with simultaneous table sliding) in 19 cases. The rapid scanning could not be evaluated in two cases because respiratory motion resulted in discontinuous image data. We were able to evaluate 34 cases. The addition of 3D images to the conventional images made it possible for us to obtain useful information on visualizing relations between nodules and vascular structures in 32% (11/34) of the cases. The 3D images enabled us to visualize the lesions and pulmonary vessels three-dimensionally. It was, however, difficult to evaluate lesion shape since we were able to obtain useful information in only 3% (1/34) of the cases. In helical scanning, data are acquired from an extensive area within a short time, providing consecutive axial-slice images remain free of any respiratory artifacts. In this regard, helical scanning is suitable for generating 3D images. A diagnostic procedure based on 3D lesion analysis should be developed and standardized. PMID- 1518162 TI - Expression of O6-methylguanine-DNA methyltransferase and chloroethylnitrosourea resistance of human brain tumors. AB - Northern blot analysis with O6-methylguanine-DNA methyltransferase (MGMT) cDNA as a probe was used to analyze the MGMT activity regulating drug resistance of human cells to chloroethylnitrosoureas (CENUs). By this method, the expression levels of MGMT mRNA in six human glioma cell lines and 12 human brain tumor tissues from surgical specimens were determined. These MGMT mRNA levels were compared with the SD10 values of the tumor cells, estimated by cell survival assay, which indicated their resistance to the anticancer drug, 1-(4-amino-2-methyl-5-pyrimidinyl)methyl 3-(2-chloroethyl)-3-nitrosourea (ACNU). Human brain tumors that were highly resistant to ACNU, such as glioblastoma Gbl1 and metastatic brain tumor Col1 with SD10 values (microM) of above 100, expressed markedly increased amounts of 0.95 kb MGMT mRNA. In contrast, tumor cells such as U-87MG, U-251MG, U-343MG, U-373MG and SF-126 with SD10 values of under 14 indicating low resistance to ACNU scarcely synthesized any MGMT mRNA. These results indicated that the level of expression of MGMT mRNA in human brain tumors determined by Northern blot analysis truly reflects their cellular resistance to ACNU. Thus the Northern method with MGMT cDNA probe reported here is a practical and reliable method for estimation of cellular resistance to CENUs such as ACNU and for screening the chemotherapeutic response to CENUs of human brain tumors. PMID- 1518164 TI - Phase I study of YK-176 (2'-deoxycoformycin) in patients with adult T-cell leukemia-lymphoma. The DCF Study Group. AB - YK-176 is a newly isolated 2'-deoxycoformycin (DCF), a potent inhibitor of adenosine deaminase, produced by Aspergillus nidulans. In a cooperative phase I study, YK-176 was administered to 22 patients, comprising 18 with adult T-cell leukemia-lymphoma (ATL), two with cutaneous T-cell lymphoma (CTCL), one with lymphoblastic lymphoma of T-cell type and one with carcinoma of the uterine cervix. Doses of YK-176 ranged from 3.0 to 9.0 mg/m2 and were given intravenously for three consecutive days. General malaise, anorexia, nausea, vomiting and low grade fever were frequently encountered, but were transient and not dose-related. At all dose levels hematological toxicities were mild. Two of seven patients receiving 7.0 mg/m2 for three consecutive days developed hepatocellular enzyme elevations (grade 2) and one patient, proteinuria (grade 2). One of two patients given 9.0 mg/m2 for three consecutive days manifested a life-threatening (grade 4) disturbance of consciousness and dyspnea, presumably ascribable to the drug related toxicity of YK-176. The results suggest that 7.0 mg/m2 i.v. for three consecutive days is the maximum acceptable dose of YK-176. Central nervous system, pulmonary and possibly renal toxicities appeared to be dose-limiting. Out of the 20 patients evaluable for therapeutic response, partial remissions were observed in four, three with ATL and one with CTCL, who received less than 7.0 mg/m2 for three consecutive days. We conclude that YK-176 is an active agent against ATL at doses that may not be associated with prohibitive toxicity. A starting dose of 5.0 mg/m2 for three consecutive days is recommended for further phase II studies on ATL. PMID- 1518165 TI - Phase II evaluation of cisplatin and 5-fluorouracil in advanced squamous cell carcinoma of the esophagus: a Japanese Esophageal Oncology Group Trial. AB - Thirty-nine patients with advanced measurable squamous cell carcinomas were treated with two or more courses of 70 mg cisplatin/m2 on day 1 and 700 mg infused 5-fluorouracil/m2 on days 1-5 every 21 days. The overall response rate was 35.9 (95% confidence limits, 24.8-55.1%). Responses were seen in primary sites in the esophagus of five patients, in the lung of seven, the liver of one and the mediastinal lymph nodes of one. The average response duration was 3.5 (range 1-12) mo for patients who achieved partial response. The average survival time after the first administration was 9.5 mo for patients who responded to the treatment whereas, for those who did not, it was 5.6 mo. The major form of toxicity was myelosuppression and there were six patients with grade 3 toxicity and one with grade 4. The present study was designed to evaluate the effectiveness of combined cisplatin and 5-fluorouracil for advanced squamous cell carcinoma, and the results showed that it had a reasonable effect and might possibly be used as a postoperative chemotherapy because of its mild side effects. PMID- 1518166 TI - Long-term clinical study on luteinising hormone-releasing hormone agonist depot formulation in the treatment of stage D prostatic cancer. The TAP-144-SR Study Group. AB - The results of long-term administration of leuprorelin acetate depot (TAP-144 SR), a sustained-release preparation of luteinising hormone-releasing hormone (LH RH) agonist, to 40 stage D prostate cancer patients who had had no previous hormonal therapy, have been analyzed. The drug was administered by subcutaneous injection once every four weeks at a dose of 3.75 or 7.5 mg. The mean duration of treatment was 480 (141-1,266) days, and treatment continued for more than one year for 60% of the 40 patients. Objective response was evaluated in accordance with Japanese Response Criteria. The best objective response in the overall evaluation was a partial response in 68.6% of the total patient group (3.75 mg, 64.3%; 7.5 mg, 71.4%). During the administration period, 21 patients were diagnosed as having progressive disease (PD), and the mean time to onset of PD was 308 days. The earliest diagnoses of PD were made on bone metastases (17 cases) and prostatic acid phosphatase levels (12 cases). The survival rate, as determined by Kaplan-Meier's method, was 81.2% (3.75 mg, 80.5%; 7.5 mg, 81.3%) two years after starting the regimen and 66.0% (3.75 mg, 65.1%; 7.5 mg, 66.0%) after three years. There was no dose dependency between either of the two drug doses, which we adopted as functions of the objective response rate, and patients' survival. Serum levels of testosterone, LH and follicle-stimulating hormone (FSH) were monitored from the first-dose until the 148th week of administration. In all patients receiving the drug as scheduled, the testosterone level was maintained at less than 1 ng/ml, and the LH and FSH levels were maintained at levels lower than their respective upper normal limits. There were no particular adverse reactions specific to the long-term administration subsequent to the foregoing 12-week administration study. In conclusion, LH-RH analogue treatment is thought to be a long-lasting, effective, palliative measure for patients with previously-untreated, advanced, prostatic cancer. PMID- 1518167 TI - Feasibility study on quality-of-life questionnaires for patients with advanced lung cancer. AB - In order to evaluate quality-of-life (QOL) questionnaires, we studied the reliability and validity of the self-rating forms: A, comprising 16 questions; B, comprising 39 questions (Table II and III), in a special study supported by the Ministry of Health and Welfare. Sixty-four patients with inoperable lung cancer and 50 patients with chronic, non-malignant disease were entered into the study. Form A was translated and modified to Japanese culture from Schipper's Functional Living Index-Cancer, and Form B was of our own design. The internal consistency of the forms was examined by Cronbach's alpha coefficient. Both forms except for aspects of physical and social concern on form B, had alpha values greater than 0.65. A concurrent validity with performance status was shown over all aspects of concern (Pearson's correlation, r greater than 0.27, P less than 0.05) except for social (forms A and B) and psychological (form B). Analysis of variance of the QOL scores revealed significantly lower scores for the cancer patients than for the non-malignant-disease patients, except for the social aspect of concern (P less than 0.001). Factor analysis, using the principal component method, identified four major factors to account for 60 and 42% of the total variance on forms A and B, respectively. The factors were: patient's mood, anxiety over disease and treatment, relationships with other people, physical capability. In conclusion, this has been the first feasible study to show that QOL forms from the West could be used in Japan with some modifications. We are at present studying successive changes in QOL for advanced lung cancer patients in clinical trials. PMID- 1518168 TI - Primary lung cancer complicated with pneumothorax. AB - Eighteen lung cancer patients with a pneumothorax complication were studied. Pneumothorax appears rarely in lung cancer patients, having been found in 18 out of 5567 (0.32%) at our hospital over a period of ten years. Of the 18 patients, eight had adenocarcinoma, seven epidermoid carcinoma and three alveolar cell carcinoma. Unlike those of previous reports, our results showed pneumothorax not to be found exclusively on the same side as the lung cancer. It was contralateral in five cases. Pneumothorax was the initial manifestation of lung cancer in three cases and occurred as a complication in another 15. Of these 15 patients, 11 were described as developing pneumothorax between one and twelve months after completion of radiation therapy for lung cancer. Another two patients developed pneumothorax following cytotoxic chemotherapy. Pneumothorax occurred prior to any treatment for lung cancer in the remaining two patients. The factors contributing to pneumothorax in the lung cancer patients were the rupture of the necrotic neoplastic tissue into the pleural cavity, the rupture of a subpleural bleb or the formation of interstitial air due to partial bronchial obstruction by the tumor, complications arising from radiation therapy and cytotoxic chemotherapy, or any combination of such factors. Pneumothorax was an ominous sign for the lung cancer patients. Most (12/14) died within six months of the onset of pneumothorax. PMID- 1518169 TI - High endothelial venules in extranodal lymphomas with emphasis on their prognostic significance. AB - In the present study, the frequency of occurrence of high endothelial venules (HEVs) in extranodal lymphomas at various sites was examined, and its prognostic implication subsequently estimated. The presence of HEVs was tested for by an immunohistochemical method using the monoclonal antibody, HECA-452, known to be specific for HEVs. The number of cases at each extranodal site were 13 in the thyroid, three in the salivary gland, 15 in the gastrointestinal(GI) tract, 20 in the brain, six in the lung, 12 in the pleura, nine in the testis, 10 in the bone, 19 in the skin and seven in the breast. Histologically, 26 of the 114 cases (23%) were of high grade malignancy according to the Working Formulation. Immunohistochemistry revealed 89 cases (78%) to be of B-cell type, eight (7%) T cell type and 17 (15%) others. HEVs were observed frequently among the cases of lymphoma of the salivary gland (100%), thyroid (77%), GI tract (53%), lung (50%) and breast (43%). Evident were a preponderance of female patients (P less than 0.02) and those with histologically favorable lymphoma types (P less than 0.001), and a more favorable prognosis (P less than 0.001) for cases with HEVs over those without. There were no significant differences in age and immunologic type distributions between cases with and without HEVs. The findings suggest that the presence of HEVs could be used as an indicator for a favorable prognosis in cases of extranodal lymphoma. PMID- 1518170 TI - Analysis of 13 postmortem examinations with regard to the effect of chemotherapy on neuroblastoma patients. AB - Thirteen postmortem examinations on neuroblastoma patients were reviewed clinicopathologically. Commonly found metastatic sites were bone, liver and lung. The introduction of massive doses of cyclophosphamide and cisplatinum into chemotherapy protocol markedly reduced the tumor burden: no tumor focus in liver or lung, small tumor burden in bone. Lymph node metastasis remained, however, and was refractory to the chemotherapy. The intensive chemotherapy caused severe side effects: interstitial or bacterial pneumonia and intrathecal bleeding, which sometimes proved fatal. Such side effects must, therefore, be carefully controlled in order to maximize the survival rate. PMID- 1518171 TI - Synchronous cancer of squamous cell carcinoma of the lung and lymphocytic leukemia (B-cell type): a case report. AB - The patient was an 82-year-old male who consulted us over a lymph node enlargement in the right side of his neck. The WBC was 23,700/microliters (lymphocytes 80%), and a diagnosis of chronic lymphocytic leukemia (CLL) was given based on the findings of a bone marrow puncture and lymph node biopsy. During the observation period, abnormal shadows accompanied by cavitation appeared in the right lower lung field, and CT-guided percutaneous biopsy findings indicated a squamous cell carcinoma of the lung. No metastatic lesions were noted. No aggressive surgical or internal treatments were performed in consideration of the patient's age. The patient was admitted again and died of respiratory failure due to lung carcinoma. Reports of CLL and other malignant tumors arising in one patient are rare in Japan, and those of their occurring concurrently are even rarer. In the present report, a case of synchronous cancer of squamous cell carcinoma of the lung and CLL is described, together with a review of the literature. PMID- 1518172 TI - Successful aggressive treatment against multiple intra-abdominal metastases from renal cell carcinoma 18 years after nephrectomy. AB - The management of late metastases from renal cell carcinoma is often difficult because of multiple organ involvement. We report a case of multiple metastases from renal cell carcinoma in the duodenum, pancreas, intestine, falciform ligament and liver, 18 years after nephrectomy. The patient underwent a total pancreatectomy following a gastroduodenal arterial embolization to control duodenal bleeding, a resection of the ileum and falciform ligament at a second laparotomy and repeated hepatic arterial embolizations to control the growth of liver metastases. Aggressive treatment should be undertaken in cases of late recurrence of renal cell carcinoma after nephrectomy because of the possibly slow growing biological character of the tumor. PMID- 1518173 TI - [Psychosomatic aspects of stress]. AB - We established the Bromocriptine test for the dopaminergic function of the hypothalamopituitary gland. The secretion patterns of plasma GH and PRL to 2.5 mg Bromocriptine, a dopamine receptor agonist, were classified into two types; a response type and a non-response type. The former showed an increase in plasma GH levels and suppression of PRL secretion; the latter showed no change in GH after Bromocriptine administration. The response type cases corresponded to psychosocial stress by neurotic and maladaptive behavior. The non-response type cases corresponded to psychosocial stress by alexithymic and over adaptive behaviors. Case Presentation 1. Essential Hypertension: a. 56-year old male, response type, blood pressure elevated by stress in daily life. Psychosomatic treatment: advice about blood pressure measurement at his home, brief psychotherapy and drug therapy. b. 53-year-old male, non-response type, type A behavior. Psychosomatic treatment: advice to increase awareness of body-mind relationships of his disorder, self-control training and drug therapy. 2. Gastric ulcers: a. 40-year-old male, response type, CMI IV region (Neurotic tendencies). Psychosomatic treatment: autogenic training and drug therapy. b. 28-year-old male, non-response type, high JAS scores(Over adaptative behavior). Psychosomatic treatment: advice to increase awareness of body-mind relationships of occurrence of his ulcers, to induce change in his perceptions of way of life, to encourage taking rest. 3. Technostress syndrome: a. 23-year-old female, response type, technoanxiety. Psychosomatic treatment: advice to make her take rest, and change in arrangements at her working place. b. 27-year-old male, non-response type, technodependent. Psychosomatic treatment: Fasting therapy. This therapy changed the non-response pattern to normal. PMID- 1518174 TI - [Stress and gastroenterology: an immunoneuroendocrinological approach]. AB - The numerous interactions between the immune and neuroendocrine systems are being studied in a rapidly expanding interdisciplinary field called "immunoneuroendocrinology" or "psychoneuroimmunology". We have recently reported that interleukin-1 (IL-1), a cytokine mainly produced by activated monocytes and macrophages, has various central nervous system (CNS) actions besides its immunological activities. Among these activities, for example, IL-1 activates the hypothalamic-pituitary-adrenal axis, a main hormonal response to stress, by stimulating the release of corticotropin-releasing factor from the hypothalamus. IL-1 also acts centrally in the brain to decrease food intake in a dose-related manner, suggesting that anorexia, a typical clinical manifestation frequently observed in acute infectious diseases, may be caused by IL-1, a cytokine that is released under such conditions as acute infection. Furthermore, we have very recently found that IL-1 has potent antisecretory and anti-ulcer actions mediated by the CNS. Based upon these results, we have proposed that there may be an "immune-brain-gut" axis, in which IL-1 acts as an afferent signal and gastric functions as efferent one. At this symposium, by presenting some of our data on the CNS effects of IL-1, we report the potential of these immunoneuroendocrinological studies for a better understanding of the pathophysiology of stress-induced gastrointestinal disorders. PMID- 1518175 TI - [Considerations in clinical testing--implications of urinary 17-ketosteroid sulfate and 17-hydroxycorticosteroid measurements for stress research]. AB - With the recent increase in number of patients with stress, the search is continuing for health-indicators that can be used to determine stress reliably and quickly. These indicators rely on subjective evaluations, and the establishment of an objective method of determining stress is necessary. We have developed a method involving the determination of the 17-Ketosteroid sulfates (17 KS-S) which has proved valuable for stress research. By simultaneous measurement of both 17-KS-S and 17-hydroxycorticosteroids (17-OHCS), which have different biological significance, and which originate from the adrenal gland, an organic Yin-Yang evaluation of the adrenocortical function can be made. The two values (mainly the 17-KS-S values) are closely correlated to the biological stress state as evaluated from psychosocial factors. This method should prove to be valuable in the clinic as an objective method of determining stress. PMID- 1518176 TI - [Primary care considerations--17-ketosteroid sulfate-17-hydroxycorticosteroid method as a clinical stress indicator]. AB - In primary care, the management of stress-related diseases occupies a wide spectrum of prevention and treatment, from holistic health care to final cure, centered on medical health and an organic integration of body, mind, and social parameters. Inquiries are being made at examinations and interviews to obtain information on the health condition of the patient, but, they are inadequate. There is a need for an objective indicator to help in the diagnosis. With the introduction of the Stress Barometer (measurements of 17-ketosteroid sulfates and 17-hydroxy-corticosteroids) it has become possible to obtain critical information on a patient in a very short time. This method allows early detection of stress, depression state and tiredness from work which is not presently possible from blood tests. It then becomes possible to call the patient's attention to these matters and to work at increasing awareness, energy levels, and responses to the conditions that are determined in this manner. PMID- 1518177 TI - [Bleeding time]. AB - Bleeding time indicates the interaction of the platelets with the damaged vessel wall and the subsequent formation of the primary hemostatic plug. Bleeding time has been widely used in the diagnosis of bleeding disorders, especially thrombocytopenia, abnormalities in platelet function, vascular disorders, and von Willebrand's disease. There are a number of methods to perform the bleeding time test, but there are significant problems concerning sensitivity, specificity, and reproducibility. To study the inhibitory effects of monoclonal antibodies (anti vWF, anti-GPIb, and anti-GPIIb/IIIa) on primary hemostasis, these antibodies were infused to normal pigs. Anti-vWF and anti-GPIb antibodies markedly prolonged the bleeding time and inhibited hemostatic plug formation. The anti-GPIIb/IIIa antibody completely inhibited ADP-and collagen-induced platelet aggregation, but no or only mild prolongation of bleeding time was observed. The quantitative bleeding time which measures both the time and the amount of blood loss is useful in the diagnosis of hemorrhagic disorders and in judging the efficacy of the treatment. It will provide important information to understand the mechanism of primary hemostasis. PMID- 1518178 TI - [Platelet aggregations and glycoproteins]. AB - Platelet membrane glycoproteins play important roles in platelet functions. In this symposium, we reported three types of deficiency of platelet membrane glycoproteins; Glanzmann's thrombasthenia, Bernard-Soulier syndrome, GPIV deficiency and discussed the roles of GPIIb/IIIa, GPIb and GPIV, respectively, in the aggregation of these abnormal platelets. In a patient with Bernard-Soulier syndrome, the abnormality in the patient's GPIb was caused by the double heterozygote from her parents who were unrelated. Roles of GPIV were negligible in platelet aggregation since the GPIV-deficient platelets (Naka-) found in healthy donors showed normal platelet aggregations. We developed two monoclonal antibodies, TM83 and TM60 against GPIIIa and GPIb, respectively, and showed that these antibodies inhibited the function of GPIb and GPIIb/IIIa complex, respectively. We demonstrated that TM83 inhibited an epitope of GPIIIa and/or GPIIb/IIIa complex which changes its conformation due to Ca2+ deprivation and is essential for exposure of the fibrinogen-binding site. PMID- 1518179 TI - [Evaluation of platelet intracellular calcium ion concentrations with flow cytometry]. AB - Platelet intracellular Ca++ ([Ca++] i) was measured by flow cytometry, using a new Ca(++)-sensitive fluorescent dye, fluo 3. The acetoxymethyl derivative of fluo 3, fluo 3 AM, was incorporated into platelets most efficiently in the presence of 1.5 micrograms/ml pluronic F-127, a surfactant often used to facilitate intracellular incorporation of lipophilic agents. [Ca++] i measurement with flow cytometry proved to be more sensitive than that with ordinary fluorescence spectrophotometers, detecting cells with elevated [Ca++] i at much lower agonist concentrations. Two-dimensional analysis using forward scatter intensities and [Ca++] i more clearly defined a subset of platelets responsive to low concentrations of agonists. In normal subjects [Ca++] i hardly changed in response to low-dose thrombin (0.002 U/ml), while it invariably showed a marked increase in response to high-dose thrombin (0.02 U/ml). Thus, these dose of thrombin were used to evaluate clinically whether platelets was hyper-reactive or hypo-reactive. Of 44 patients with diabetes mellitus, 6 patients had hypo responsive platelets, while platelets were sensitive to low concentrations of thrombin in 3 patients. Since such differences cannot be detected by conventional spectrophotometric methods, [Ca++] i measurement by flow cytometry may prove useful tool for clinical evaluation of platelet function. PMID- 1518180 TI - [Analysis of platelet shape change, inositol metabolism, and Ca mobilization in patients with platelet dysfunction]. AB - Agonists-induced platelet shape change, inositol metabolism, and Ca mobilization were investigated in patients with various platelet dysfunctions. The platelet shape change determined by our method revealed that arachidonate-induced platelet shape change was completely defective in patients with cyclo-oxygenase (CO) deficiency (A). STA2-induced platelet shape change was also defective in one of five patients with impaired aggregation to STA2 (B). Thrombin-induced platelet shape change was weak in patients with Bernard-Soulier syndrome. In patient with Hermansky-Pudlak syndrome, the platelets did not respond normally to STA2, arachidonate or PMA. These findings suggested that the determinations of platelet shape change by our method was useful in diagnosing platelet dysfunctions. Inositol metabolism and Ca mobilization in response to thrombin, STA2, or NaF were also investigated in patient A,B, and impaired aggregation to A23187 in patient C. The responses were normal in patient A, suggested that CO activity did not affect them. Inositol metabolism was also normal in patient C, although Ca mobilization in response to A23187 was delayed, and that in response to thrombin was defective in the absence of extracellular Ca2+. This suggests that the patient's platelets have a defective IP3-induced Ca mobilization pathway. STA2 selectively failed to induce IP3 formation and Ca mobilization in patient B, although 3H-labelled thromboxane ligand (3H-U46619) bound to the patient's platelets, normally. These findings suggested that the patient's platelets have a defect in postreceptor signal transduction, especially thromboxane receptor mediated phospholipase C activation pathway. PMID- 1518181 TI - [Determination of serum interleukin-6 concentration by an enzyme-linked immunosorbent assay in patients with paraproteinemia]. AB - A sensitive enzyme-linked immunosorbent assay of human interleukin-6 (IL-6) was developed to measure the serum IL-6 by Fujirebio INC. Its sensitivity was 3 pg/ml and its analytical range was from 3 to 200 pg/ml. Its precision, reproducibility, and sensitivity were quite satisfactory. The serum IL-6 levels in 200 normal individuals were less than 3 pg/ml. Serum IL-6 concentration in patients with malignant and benign monoclonal gammopathy (BMG) was determined by an ELISA. Serum IL-6 concentration in patients with Bence Jones protein (BJP) type multiple myeloma (MM) (n = 12) was 12.3 +/- 12.7 (mean +/- SD) pg/ml, BJP and IgG type MM (n = 4) 11.5 +/- 5.8 pg/ml, IgM type MM (n = 11) 11.1 +/- 17.5 pg/ml and IgA type MM (n = 4) 4.0 +/- 1.4 pg/ml. They were significantly higher in BJP, BJP and IgG, and IgM types than in normal individuals. The cases with the serum IL-6 of more than 10 pg/ml were move frequent in MM (32.8%) than in BMG (16.3%). The correlation between the serum IL-6 and C-reactive protein (CRP) was r = 0.563 in patients with MM (n = 61) and r = 0.498 in BMG (n = 43). Besides, during the clinical course of a patient with IgG-lambda and BJP-lambda type MM, serum IL-6 concentration responded more sharply than CRP and WBC on candida infection. The measurement of serum IL-6 therefore, seemed not useful for differential diagnosis of monoclonal gammopathies, but it seemed useful as an acute phase protein as well as CRP. PMID- 1518182 TI - [Inhibitory effect of ulinastatin on the alpha-thrombin activation of factors V and VIII]. AB - Ulinastatin is a remedy of urine serinprotease inhibitors and also it inhibits enzymatic activities of several blood coagulation factors. The action of ulinastatin on alpha-thrombin shows noncompetitive inhibition with the formation of enzyme-inhibitor complex. In this study, the effects of ulinastatin on the alpha-thrombin activation of factors V and VIII are observed by 5-20% gradient gel SDS PAGE with or without Western blotting method. The addition of ulinastatin to the mixture of factor V and alpha-thrombin inhibits the production of active peptides proceeded in the alpha-thrombin activation process of factor V. Furthermore, using anti-factor VIII 43KDa peptide monoclonal antibody with Western blotting method, the addition of ulinastatin to the mixture of alpha thrombin and factor VIII indicates to inhibit the release of 43KDa peptide from factor VIII in the process of factor VIII activation induced by alpha-thrombin. PMID- 1518183 TI - [Analysis of factors affecting anaerobic threshold in healthy subjects]. AB - The anaerobic threshold (AT) is used to determine the exercise capacity in patients with heart failure and healthy subjects. To determine the factors affecting AT, we determined the AT in healthy subjects, and examined the factors that determine AT in healthy subjects. One hundred and sixteen healthy subjects (79 men and 37 women) performed on a bicycle a stepwise increasing submaximal exercise. During the work test the parameters usually used in the detection of AT (Vo2, Vco2, VE), blood pressure, heart rate and oxygen saturation were recorded by a computerized system every minute. AT was determined from changes in ventilation and gas-exchange. The fat index was calculated from height and body weight measured at the beginning of the ventilatory function test. A significant correlation was obtained between AT and age, AT and fat index, AT and %VC, AT and maximum heart rate during exercise, AT and recovery rate of heart rate after exercise, and AT and Vo2 at rest. In addition, we examined the relationship among the parameters in 4 groups according to sex and age (30-49; younger, 50-69; older), because sex and age affected most parameters. We found a significant correlation between AT and fat index (older men and women), AT and %VC (younger and older women), AT and Vo2 at rest (younger and older men). We considered that the main factors that determined AT in healthy subjects were age, sex, fat index, %VC and Vo2 at rest. PMID- 1518184 TI - [Serum HDL-cholesterol in patients with breast carcinoma]. AB - To extend our previous findings on lipid metabolism in breast carcinoma, serum levels of cholesterol and HDL-cholesterol in 144 patients with breast carcinoma, 64 patients with cervix carcinoma, 52 patients with benign breast diseases and 83 healthy females were determined. Blood samples, obtained from patients with carcinoma of the breast and the cervix, were taken prior to radical surgery and at the time of sampling, none of them had received chemotherapy and/or total intravenous nutritional therapy. No significance was observed in the serum levels of cholesterol between the patients with carcinoma, benign diseases and healthy females. The serum levels of HDL-cholesterol, measured by the heparin-calcium nickel precipitation method were lower among the patients with breast carcinoma than among the patients with cervix carcinoma and healthy females. The mean values and S.D.s of serum HDL-cholesterol of the patients in stage I (23), II (35) and (7) were 42.0 +/- 14.7, 36. 4 +/- 13.1 and 28.7 +/- 9.5 mg/100 ml, respectively, exhibiting a tendency to decrease with the increase in malignancy. PMID- 1518185 TI - [Recommendation for large scale intervention study on industrial population]. PMID- 1518186 TI - [Between- and within-subject variability of pulmonary function. Four year follow up of adult males]. AB - Maximal forced expiration of 326 adult males 30 to 55 yr of age was measured four times during a follow-up of 4 yr. Acceptable results were obtained in 270 subjects three times or more. Forced vital capacity (FVC), forced expiratory volume in one second, maximal expiratory flows at 50% and 25% FVC divided by squared height (CFVC, CFEV1, CVmax50, and CVmax25, respectively) were analyzed. Between- and within-subject variance were estimated by a linear model, including the effects of individual and age as explanatory variables. The goodness of fit of the model was satisfactory, since the coefficients of determination of the model were more than 0.96 for CFVC and CFEV1 and around 0.91 for CVmax50 and CVmax25. Estimated between-subject variance was far larger than within-subject variance, being more than ten times for CFVC and CFEV1, about eight times for CVmax50, and five times for CVmax25. At the same time, annual decline of pulmonary function determined cross-sectionally was significantly larger than that determined longitudinally. These results indicated the superiority of longitudinal analysis to cross-sectional analysis in evaluating relatively small effects on pulmonary function especially in the case of chronic exposure of toxic substances in low doses. PMID- 1518187 TI - [Risk factors of cerebro-cardiovascular events in treated hypertensive male workers in the fifth decade]. AB - The relationship between cerebro-cardiovascular events (CCE) and work-related factors was examined in a cohort of 899 treated hypertensive men who were aged 50 59 yr and working more than 7 portal to portal hours (PPH). During the follow-up of 2.8 yr (2,513 person-years), 27 cases of CCEs occurred, which were classified into 18 cases of stroke, 7 cases of acute myocardial infarction, and 2 cases of others. Using univariate analysis, it was found that managerial position and long PPH (more than 11 h) were significantly related to CCE (relative risk of 3.0 and 2.2, respectively) as well as risk factors such as emaciation, left ventricular hypertrophy, excessive sleeping hours, obesity, cigarette smoking, and inadequate control of systolic blood pressure. Using Cox proportional hazards general model, both managerial position and long PPH remained independently related to the risk of CCE (hazards ratio and 95% confidence interval, 4.1; 1.7-10.0 and 2.7; 1.1 6.2, respectively), after adjustment for other risk factors. These findings suggested that work-related factors, such as managerial position and long PPH, are independent risk factors of CCE among treated hypertensive male workers in the fifth decade. PMID- 1518188 TI - [Health condition of female aerobic dance instructors. Subjective symptoms and related factors]. AB - Aerobic dance has recently become popular in all age groups, but the injuries among full-time and part-time aerobic dance instructors have rarely been pointed out in Japan. In this study the subjective symptoms of 63 female instructors in Gifu area were evaluated through health questionnaire. As a control group, 94 female students of the same age group were also included to compare the prevalence of subjective symptoms. Multiple logistic regression analysis was applied to observe the relation between instructors' symptoms and working conditions. The following results were obtained: 1) Complaints of leg and foot pain and laryngeal discomfort were significantly greater in instructors than in students even after adjusting for age and participation in other sports. 2) A significant positive relation was found in instructors between the frequency of dance lessons (times/wk) and various symptoms (calf pain, foot pain, sore throat, and hoarse voice) after adjusting for age and participation in other sports. These results suggest that leg and foot pain and laryngeal discomfort are characteristic symptoms of aerobic dance instructors. Consideration should be made to adjust the frequency of dance lessons in order to reduce these symptoms. PMID- 1518189 TI - [A simple method for measuring cleaning solvent in air by gas detector tube for ethyl acetate]. AB - A simple method for measuring cleaning solvent in air by gas detector tube for ethyl acetate was evaluated with regard to basic performance such as sensitivity, precision, discolor tone and effect of temperature. Satisfactory results were obtained with regard to sensitivity, precision, discolor tone in the indicator and stability of discolored length. Range of measurable concentration by the present method was about 25-800 mg/m3. It was found necessary in the present method to make temperature correction. It was concluded from these results that the present method is useful for measuring cleaning solvent in air. However, positive effect on discolored length was found by vapor of toluene and ethyl acetate when they coexisted. No effect on discolored length was found by vapor of acetone, methanol or trichloroethylene. PMID- 1518190 TI - [Sex difference in free erythrocyte protoporphyrin (FEP) level. I. Sex difference in FEP level in healthy rural residents]. AB - FEP and other hematological parameters were measured in 157 healthy rural residents (98 females and 59 males). The mean FEP in females was higher than in males (p less than 0.05); mean +/- SD = 62.98 +/- 19.36 and 54.57 +/- 21.20 micrograms/dl.pcv, respectively, although both of the means were within normal limits. There was no significant sex difference in erythrocyte ALA-D activity. Whole blood lead (Pb-B) level in females showed a tendency to be lower than in males, but there was no significant sex difference in erythrocyte lead level. The mean value of hematocrit (Ht), hemoglobin (Hb) and iron in serum (Fe-S) were lower in females than in males (p less than 0.01). Serum GOT and GPT level tended to be lower in females than in males (0.05 less than p less than 0.1). There was hardly any significant relationship between Pb-B and each parameter of lead exposure, because the subjects in this study were only rural residents with no occupational lead exposure and with their Pb-B levels being extremely low. As for the parameters of anemia, Fe-S was positively correlated with Ht and Hb level and negatively correlated with FEP level. By sex, Fe-S was correlated with Ht and FEP level only in females. As for the possible reasons why FEP level in females in higher than in male, women tended to have iron-deficiency induced by blood loss due to menstruation, pregnancy, and difference in dietary pattern from males. PMID- 1518192 TI - [Effects of N,N-dimethylformamide on hepatic drug metabolizing enzymes in rats]. PMID- 1518191 TI - [Sex difference in free erythrocyte protoporphyrin (FEP) level. II. Sex difference in FEP level in rats exposed to lead]. AB - An experimental study on Donryu rats was primarily carried out to elucidate sex difference in FEP level. Each of 33 male and 33 female rats was divided into 3 groups; that is, control group (5% glucose solution only), low lead dose group (Pb 0.5 mg/kg.BW) and high lead dose group (Pb 5 mg/kg.BW). Lead was injected intraperitoneally once a week for 6 wk. FEP, Ht, urinary coproporphyrin (CP-U), delta-aminolevulinic acid (ALA-U) and porphobilinogen (PBG-U) were determined once every two weeks for 6 wk, and whole blood lead (Pb-B) at the end of the experiment. Mean value of Ht was lower in females than in males throughout the period of the experiment in almost all groups. Pb-B level of all groups and erythrocyte Pb level of high dose group were higher in males than in females. FEP level without lead injection and with low lead exposure was higher in males than in females. By analysis of variance for gain from initial FEP level, only the low lead dose group demonstrated a significant sex difference (p less than 0.01); the female group tended to increase, while the male group maintained a constant level. Furthermore, FEP/Pb-B ratio in females was higher than in males only for the high dose group. The changes in ALA-U in male and female rats were comparable to those in FEP. Unlike FEP and ALA-U, CP-U level was higher in males than in females only for the high lead dose group. In this study using rats, sex difference in FEP level was different from that in human.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1518193 TI - [Effect of short-term blood pressure variance on blood pressure classification]. PMID- 1518194 TI - [32nd general meeting of the Japanese Society of Nuclear Medicine. Yokohama, Japan, September 24-26, 1992. Abstracts]. PMID- 1518195 TI - [Total aortic arch graft replacement using a prosthetic graft with three branches for acute type A aortic dissection]. AB - Between March 1991 and August 1991, six consecutive patients underwent the replacement of the both ascending aorta and total aortic arch using a prosthetic graft with three branches for acute type A aortic dissection involving the aortic arch. Preoperative complications included cardiac tamponade in 5 cases, aortic regurgitation in 2, and shock state in 3. All operations were performed with the aid of extracorporeal circulation, selective cerebral perfusion, and open aortic anastomosis within 3 days after the onset. One patient died of rupture of the aortic anastomosis secondary to mediastinitis two weeks after the operation. All patients gained their own consciousness after the operation without any serious cerebral complications. The present data suggest that acute type A aortic dissection involving the aortic arch could be treated by replacing both the ascending aorta and aortic arch using a prosthetic graft with three branches with an aid of the extracorporeal circulation, selective cerebral perfusion and open distal anastomosis. PMID- 1518196 TI - [Postoperative respiratory dysfunction in patients with Stanford type A aortic dissection]. AB - Between 1986 and 1990, 24 patients with Stanford type A dissection (acute; 14, chronic; 10) underwent surgery through median sternotomy. The patients were divided into two groups by a duration of postoperative ICU stay for respiratory care. Six patients in the long-period group stayed in ICU for more than 15 days and 18 patients in the short-period group stayed for less than 15 days after surgery. Acuity of disease, age, sex, operation time, pump time, aortic clamp time, lowest esophageal temperature, amount of blood transfusion, arch manipulation for cerebral perfusion with or without arch reconstruction, occurrence of phrenic nerve palsy and other postoperative complications, postoperative cardiac, hepatic and renal functions were compared between two groups. Conclusions are as follows: 1) Arch manipulation for cerebral perfusion with or without arch reconstruction, phrenic nerve palsy, other complications (pericardial and pleural fluid accumulation, recurrent nerve palsy, postoperative bleeding and coronary spasm) and high serum creatinine level were main factors for prolonged postoperative ICU stay for respiratory care and 2) arch manipulation in the patients with chronic type A aortic dissection induced high incidence of phrenic nerve palsy. PMID- 1518197 TI - [Total aortic arch replacement through a median approach]. AB - Seven patients underwent total aortic arch replacement only through a median approach since March 1990, in our institute. The woven Dacron graft with three side arm branches were used. After the proximal anastomosis at the ascending aorta, open distal anastomosis at the descending aorta was performed in five cases, under circulatory arrest of the lower body using separate perfusion to the brain. In two cases with true aneurysms involving the aortic arch, occlusion balloon catheters were employed for distal anastomosis. The anastomosis of the arch vessels was performed after coronary reperfusion. There was no early operative death, and our results demonstrate that total arch replacement can be safely accomplished through a median approach with an acceptably low operative risk. PMID- 1518198 TI - [Basic study of myocardial coagulation by intraoperative laser ablation: in the presence and absence of blood]. AB - To investigate whether the efficacy of laser ablation therapy is affected by the color of the target organ, we irradiated 9 canine hearts through the epicardium with Nd-YAG laser (200 J, 400 J), and compared coagulated myocardial volume in the beating heart (reddish) with that in the stopped heart (whitish) infused with 0 degrees C saline (cardioplegic model) via a coronary artery. The coagulated myocardial volume of the beating heart was significantly larger than that of the arrested heart, indicating the YAG laser energy is absorbed by red myocardium to greater extent than it is by white myocardium. In conclusion, during intraoperative laser ablation, the presence or absence of blood in cardiac tissue is an important factor for safe irradiation. PMID- 1518199 TI - [Autogenous pericardial patch augmentation of the anastomotic orifice of Blalock Taussig shunt]. AB - Our recent experiences of the autogenous pericardial patch augmentation of Blalock-Taussig anastomotic orifice are reported. In Case 1, the direct suture between the left subclavian artery and the left pulmonary artery was difficult on the anterior wall because of the shortness of the left subclavian artery. Therefore, a piece of the patient's own pericardium was excised and sutured anteriorly between the two vessels by interrupted 7-0 polypropylene sutures. A 19 months postoperative angiogram showed so-called parrot-beaking of the subclavian artery probably due to tension, but there was no distortion or stenosis of the pulmonary artery. In Case 2, the right subclavian artery distal to the bifurcation of the vertebral artery was longitudinally split measuring approximately 2.5 cm in length, and widened by a piece of the autogenous pericardium in a wedge shape. Then, it was anastomosed to the right pulmonary artery without undue tension. Seven months postoperatively the patient died from severe AV valve regurgitation. The autopsy showed widely patent anastomosis and good healing as well as slight expansion of the pericardial patch but without aneurysm formation. In Case 3, the same operation as in Case 2 was performed. A 6 months postoperative angiogram showed no stenosis or distortion of either the subclavian or the pulmonary artery. Although it is premature to draw any conclusion, the use of the autogenous pericardium may be indicated to widen the anastomotic orifice of Blalock-Taussig shunt without sacrificing the length of the subclavian artery even in small infants or neonates. PMID- 1518200 TI - [Surgical treatment of total anomalous pulmonary venous connection Darling type Ib using pedicled right atrial flap]. AB - A one-month-old baby with total anomalous pulmonary venous connection (TAPVC) type Ib underwent a total correction with a pedicled right atrial (RA) flap, which was made by incising the RA wall in a quadrangular configuration. The common pulmonary vein (PV) was cut back into the left atrium (LA). Then the RA flap was sutured along the limbus of PV recess and atrial septal defect (ASD) to create a new pulmonary venous channel. The defect in the RA wall was directly closed without any prosthetic patch. Absorbable sutures (# 6-0 PDS) were used throughout. Postoperative course was uneventful and echocardiogram showed widely opened PV channel draining into the LA. We think that this procedure could be applied in various types of total and partial anomalous pulmonary venous connection, avoiding pulmonary venous obstruction on the assumption that the RA flap should grow. PMID- 1518202 TI - [Report of three cases of emergency surgical salvage for acute pulmonary embolism]. AB - Pulmonary embolism (PE) is one of the increasing diseases in Japan, which is aggravated rapidly and early diagnosis is necessary to improve its prognosis. We experienced three cases of successful surgical salvage. It is emphasized that the Doppler ultrasonic echocardiography plays important part in diagnosing PE early and noninvasively. Namely, it shows a appearance of acute cor pulmonale, and is usually able to guess the pulmonary artery pressure by using the simplified formula of Bernoulli's equation. We believe that the surgical pulmonary embolectomy under the cardiopulmonary bypass should be immediately considered in case of unsatisfactory conservative thrombolytic therapy. PMID- 1518201 TI - [Surgical treatment of dissecting aortic aneurysm using GRF glue]. AB - A 62-year-old woman underwent primary anastomosis for dissecting aortic aneurysm (DeBakey IIIb) using GRF glue. GRF glue consists of mixture of gelatin and resorcin. The mixture is hardened by the addition of medical formaldehyde. Resorcin is diphenole which reacts with formaldehyde, creating tridimentional network. Primary anastomoses were performed after the lumen of dissected aorta was adhered with GRF glue. It appears that primary anastomosis using GRF glue is a simpler and safer operative method for dissecting aortic aneurysm. PMID- 1518203 TI - [Surgical treatments of emphysematous giant bullae accompanied with severe bronchial asthma]. AB - Two operative cases of emphysematous giant bullae of the lung accompanied with bronchial asthma were reported. Case 1: A 41-year-old man suffering from dyspnea and fever-up was diagnosed as emphysematous giant bullae of the right lung accompanied with severe bronchial asthma. Preoperative examination revealed severe hypoxemia (PO2 46 mmHg) and mixed type ventilatory disorder; VC 1.68 t (41%), FEV1.0 0.59 l (35%). On the first anesthesia, operation was postponed by the severe asthmatic attack and circulatory collapse. After the complete prevention of the attack by giving corticosteroid (25 mg/day) for two weeks, resection of giant bullae could be performed safely. Case 2: A 31-year-old man complaining wheeze was diagnosed as emphysematous giant bullae of bilateral upper lobes of lung accompanied with bronchial asthma. Preoperative and intraoperative states were uneventful, though, on the day after the operation, asthmatic attack occurred due to the difficulty in expectation of sputa. It took 12 hours and many kinds of drugs to improve the respiratory state. In the patients of bronchial asthma, preoperative sufficient suppression of hyperreactivity of airway tracts and postoperative careful treatment to avoid asthmatic attack seem to be indispensable. PMID- 1518204 TI - [Limits of duration of chest tube drainage in the first episode of spontaneous pneumothorax]. AB - We treated three patients with spontaneous left pneumothorax who underwent a long period of chest tube drainage before surgery. Case 1 was a 61-year-old man. On day 13 after drainage started, much air leakage occurred and surgery was done the next day. Case 2 was a 57-year-old man. Drainage failed to allow the air leakage to seal. The patient did not consent to surgery for about a month, but on day 38 after drainage started, he underwent surgery. Case 3 was a 19-year-old man. First, chest tube drainage was successful and he was extubated on day 16. However, pneumothorax recurred the next day. Liver dysfunction delayed surgical treatment, and the patient underwent surgery on day 54 after the first drainage. Postoperatively, he developed wound infection of the chest tube route and aseptic pleurisy of unknown origin. Limits of duration of unsuccessful chest tube drainage for the first episode of spontaneous pneumothorax are controversial. These cases suggest that when two weeks of chest tube drainage is unsuccessful, surgery should be undertaken in view of postoperative complication and social indications. PMID- 1518205 TI - [Combined revascularization of coronary and femoral arteries]. AB - A 63-year-old male patient with both coronary artery disease and leg ischemia was successfully treated with a combined procedure. Coronary arteries were bypassed with the saphenous vein graft and in situ left internal mammary artery, and bilateral femoral arteries were bypassed with expanded polytetrafluoroethylene grafts descended from the ascending aorta through the preperitoneal abdominal wall tunnel. After this procedure he experienced neither angina nor claudication. PMID- 1518206 TI - [A case of enchondroma protuberance with destroying the rib bone]. AB - A 42-year-old female was referred to our hospital because of a tumor shadow in the right lung fields. Tomography revealed a tumor which had destroyed the right 4th rib. Under the diagnosis of malignant tumor, she was treated by radical en bloc excision. The pathological diagnosis was enchondroma. PMID- 1518207 TI - [A case of invasive thymoma which had grown in the SVC via left innominate vein through thymic vein]. AB - A 66-year-old male was referred to our department with mediastinal tumor. The chest X-ray and the chest CT showed a large tumor adjacent to pulmonary artery and descending aorta. Cavogram revealed a filling defect of the SVC. He underwent complete resection of the tumor, resection of the SVC and reconstruction of the SVC with ringed PTFE. The main tumor was 12 x 7 cm in size and the tumor in the SVC was 20 x 15 mm in size. Histopathological findings showed a lymphocytic thymoma. Compact invaded nest of tumor cell was found in the innominate vein. The tumor in the SVC was invasive to the intima of the SVC, but its media and adventure were intact. This case is rare among patients with invasive thymoma as far as the growth is concerned. PMID- 1518208 TI - [A case of incomplete endocardial cushion defect with mirror-image dextrocardia, IVC defect and azygos connection]. AB - A case of incomplete endocardial cushion defect associated with mirror-image dextrocardia, IVC defect and azygos connection is reported. Intracardiac defect was corrected under moderate hypothermia with cardiopulmonary bypass. Three venous drainage cannulas were necessary to be indwelled into SVC, hepatic vein and right common iliac vein to maintain adequate venous drainage for extra corporeal circulation. Thus, anomaly of venous system, which is commonly associated with mirror-image dextrocardia, must be recognized correctly and prepared before intracardiac correction. PMID- 1518209 TI - [Chemo-thermotherapy of radiation-induced squamous cell carcinoma in anterior chest wall]. AB - A 62-year-old woman had visited our hospital with the large and deep ulcer formation on the left anterior chest wall. A biopsy of the ulcerous lesion established the diagnosis of a squamous cell carcinoma which might be induced by the irradiation after mastectomy. Although a wide resection of the chest wall including left arm was performed, it was impossible to resect completely. After then, she had operations for local recurrence for three times in three years. However, cure was not obtained, and residual lesions gradually enlarged and all layers of the anterior chest wall was replaced with tumor tissues. Conventional chemotherapy using ftorafur and mitomycin C was not effective. Therefore, we tried combined therapy with intravenous administration of cisplatin (CDDP) and vindesine (VDS), and local hyperthermia using radiofrequency (RF) wave. A total number of 11 courses of this treatment modality was carried out at once a week intervals. The tumor-temperature was maintained at the range of 40-43 degrees C for 40 min in each treatment session. Chemotherapeutic agents were administered simultaneously with hyperthermia. After these treatments, the recurrent tumor was markedly reduced, and epithelization of the ulcer was recognized from the surrounding normal skin. The residual tumor was then resected completely. The operative wound was successfully closed by surrounding normal tissue mobilization. She is in good postoperative condition. We concluded that the chemo thermotherapy is safe and promising therapeutic modality for such invasive squamous cell carcinoma, and the normal tissues are not affected. Furthermore, this approach will expand the scope of radical resection for such an uncontrollable tumor. PMID- 1518210 TI - [A surgical repair of complete endocardial cushion defect associated with single atrium, persistent left superior vena cava draining into the left atrium, hemiazygos connection and double orifice mitral valve]. AB - Successful surgical repair of a 1-year-old girl of complete endocardial cushion defect associated with single atrium, persistent left superior vena cava draining into the left atrium, hemiazygos connection and double orifice mitral valve was reported. We repaired the endocardial cushion defect by using an endocardial cushion prosthesis and a new atrial septum was created to allow the left superior vena cava draining into the right atrium. We made no treatment for the accessory mitral valve orifice because of no regurgitation. PMID- 1518211 TI - [A case report: an elderly patient surviving conservative surgical repair of ventricular septal perforation (VSP) with using Swan-Ganz catheter in order to close VSP temporarily]. AB - A 81-year-old female was referred to our hospital for VSP. Preoperative catheterization showed that pulmonary arterial pressure (PAP) was 50 mmHg over in systole, and L-R shunt rate was 63.4%. In spite of any medications under intraaortic balloon pumping, hemodynamics was gradually worsened. And so Swan Ganz catheter was inserted into right ventricle via VSP retrogradely in order to close VSP with the balloon of the catheter. PAP decreased to about 40 mmHg in systole and L-R shunt rate became to 49.7% by this method. This treatment could conserve the surgical repair for 5 days and the operation was performed on 22 days after the onset of VSP. It is very important to be able to conserve VSP operation by using Swan-Ganz catheter to close VSP temporarily. PMID- 1518212 TI - [A successful surgical case of acute myocardial infarction in total obstruction of the left main coronary arterial ostium]. AB - Cardiogenic shock due to acute myocardial infarction in an 81-year-old man with total obstruction of the left main coronary arterial ostium was successfully treated with coronary artery bypass grafting. Although this procedure was successful there are some problems in the surgical management of this condition with regard to myocardial protection and preoperative evaluation of poorly visualized left coronary system. It is necessary to infuse first a large volume of high pressure cardioplegic solution and then follow it with another infusion of the solution, through the vein graft, at the regular volume and pressure. Furthermore, the complete revascularization of the left coronary system by vein grafts is recommended. PMID- 1518213 TI - [A case of emergency operation of entrapped intra-aortic balloon]. AB - We report a case of emergency operation for entrapped intra-aortic balloon. The cause of entrapment of balloon was formation of a clot inside the balloon, which necessitated surgical removal. When intra-aortic balloon rupture by contact of calcific atheromatous plaque, the alarm is not often triggered. In this case, perforation is diagnosed by the presence of blood in the tube connecting the balloon. It is recommended that the balloon should be removed at the presence of blood in the tube. PMID- 1518214 TI - [Pseudocoarctation associated with dissecting aneurysm of the aorta: a case report]. AB - A case of pseudocoarctation with dissecting aneurysm of the ascending aorta and arch is reported. A 49-year-old man was admitted with chest pain and loss of consciousness. Angiogram showed kinking of the aortic isthmus and dissecting aneurysm of the ascending aorta. There was no pressure gradient between arms and legs. Prosthetic graft replacement of the ascending aorta was successfully performed by the use of total cardiopulmonary bypass with moderate hypothermia. Etiology of the development of pseudocoarctation is unknown, however, hypothesis that embryological abnormality of the aortic arch is one of the contributing factors has been widely accepted. This case was accompanied by bicuspid aortic valve. It is suggested that the developmental etiology of this case seems to be similar to that of classical coarctation of the aorta. Development of the dissecting aneurysm is supposed to be due to hypertension of the upper body during exercise, even though there is no pressure gradient at rest. PMID- 1518215 TI - [Preoperative preparation and surgical treatment of elderly and very old patients with abdominal hernia]. AB - On the basis of analysis of the results of treatment of 312 elderly and senile patients with abdominal hernia, it was established that performance of adequate preoperative preparation permitted considerable extension of indications for the operation. Contraindications for surgical treatment of such patients should be established after performance of preoperative preparation with regard for indices of external respiration and hemodynamics. PMID- 1518216 TI - [The use of sonic waves in the treatment of motor disorders of the upper alimentary canal in the early postoperative period]. AB - The effect of sonic waves on motor activity of the stomach, duodenum, extrahepatic bile ducts in 152 patients at the early postoperative period was studied. Motor activity was assessed on the basis of findings of clinical investigations, electrogastroenterography, balloon tensiomanometry, cholangiodebitomanometry. It was established that influencing with the sonic waves with a frequency of 2.5 kHz, intensity of 0.66 W/cm2 2 times a day for 10 15 min within 1-3 days contributed to rapid stable restoration of motor activity of the upper alimentary canal in 86.6% of the patients. PMID- 1518217 TI - [Surgical technique and approaches in orthotopic liver transplantation]. AB - The first clinical experience with orthotopic transplantation of the liver was summarized. Within the period of from February 1990 to May 1991, 8 operations were performed, including one retransplantation of the liver. The peculiarities and variants of surgical technique, general principles of the performance of operation, methods for vascular and biliary reconstruction are presented. After the operation, 3 patients are alive, no surgical complications were observed. PMID- 1518218 TI - [Formation of closed aseptic anastomosis of the hollow organs with the use of laser]. AB - The authors modified the method for formation of aseptic anastomosis, using radiation of the CO2-laser and neodymium-doped YAG laser. The techniques for placing the enteroenteric anastomosis, gastroentero- and cholecystojejunoanastomosis are presented. Reduction in incidence of inflammatory and purulent postoperative complications has been achieved. PMID- 1518219 TI - [Surgical treatment of patients with obstructive jaundice]. AB - The results of treatment of 481 patient operated on for obstructive jaundice have been analysed. In 388 (80.7%) patients, jaundice was caused by non-tumor lesion of the bile ducts. At the peak of jaundice, operated on were 312 (64.9%) patients, who experienced no benefit from conservative therapy. The tactics for operative intervention was chosen individually with regard for the cause of jaundice, concomitant pathology and age of a patient. The main cause of death was the aggravating hepato-renal failure due to prolonged jaundice and late hospitalization. PMID- 1518220 TI - [Use of acelysin solution in the treatment of acute purulent inflammatory diseases of soft tissues]. AB - The authors have successfully used for local treatment of purulent wounds a new preparation acelysin. In animals with the induced abscesses, under the influence of acelysin, more rapid recovery than in the control group of animals treated with hypertonic sodium chloride solution, dioxidine solution was achieved. The effectiveness of treatment was judged by duration of the course of a wound process, findings of morphologic, cytologic and bacteriologic studies. Use of acelysin solution in 24 patients with suppuration of an operative wound has confirmed its effectiveness. PMID- 1518221 TI - [Effectiveness of ultraviolet irradiation of the blood of patients with purulent inflammatory diseases and its effect on the natural resistance]. AB - In the complex treatment of 121 patient with purulent-inflammatory diseases with the aim of detoxication, reinfusion of the blood irradiated with ultra-violet rays was used. Judgment about the effectiveness of treatment was based on the findings of clinical and laboratory studies. There were no complications. In 8 patients, a hyperthermal reaction occurred. Under the influence of irradiation, a quantity of the natural killer cells has normalized, while in the control group, it was smaller than in healthy subjects. PMID- 1518222 TI - [Surgical treatment of inguinal hernias in elderly and very old patients]. AB - The results of surgical treatment of inguinal hernias in 315 war veterans, including 260 the elderly and senile, have been analysed. All the patients underwent the elective operations. Four (1.2%) patients developed complications after the operation, there were no lethal outcomes. The authors came to a conclusion about the expediency to perform elective herniotomy in elderly and senile patients even in presence of concomitant diseases. PMID- 1518223 TI - [Significance of the separate symptoms in acute appendicitis]. AB - On the basis of the experience with treatment of 19,346 patients with acute appendicitis, the authors have established that pain in the right inguinal region, rigidity of muscles of the anterior abdominal wall, and a Volkovich Kocher symptom were the most informative symptoms. The Shchetkin-Blumberg symptom caused by the development of an inflammatory process in the peritoneum is not an appendicular symptom; the Rovzing, Voskresensky, Obraztsov symptoms, not being the specific symptoms of acute appendicitis, are of essential informative value only in combination with the other symptoms of the disease. PMID- 1518224 TI - [Treatment of ligature fistulas after appendectomy]. AB - On the basis of clinical examples, the danger of ambulatory treatment of a ligature fistula is shown. To prevent its development, a care of tissues is necessary: in cases of technical difficulties, a wound should be widened, fat and muscles isolated, a wound before closure needs mandatory irrigation with antiseptic solutions. Ineffectiveness of conservative treatment of a fistula during 1-2 weeks requires the operative intervention in a specialized department with excision of purulent necrotic masses and ligature which maintains the inflammation. Before wound closure, a perforated drain for flowing irrigation should be established. PMID- 1518225 TI - [Foreign bodies in the rectum and colon]. AB - On the basis of analysis of treatment of 80 patients with foreign bodies of the rectum and colon, the volume and character of the therapeutic measures required were defined. The endoscopic methods for removal of the foreign bodies, peculiarities of extraction of the large foreign bodies are presented. The cases of penetration of the foreign bodies into the colon via a natural, or artificial intestinal fistula are described. PMID- 1518226 TI - [Intratissue electrophoresis in patients with appendicular colic and a preliminary diagnosis of non-destructive acute appendicitis]. AB - The possibility of the use of intratissue electrophoresis in patients with presumptive diagnosis of acute appendicitis was studied. Use of the method suggested contributes to enhancing the effectiveness of the treatment performed, prevents unsubstantiated performance of appendectomy, shortens time patients stay in a hospital. The long-term results of treatment with the use of intratissue electrophoresis are better than those in use of the existing methods of dynamic observation (parenteral administration of spasmolytic and desensitizing agents). PMID- 1518227 TI - [Reconstruction of the anus in marginal necrosis of the lowered intestine after abdominal-anal resection]. AB - The experience with treatment of a most frequent complication after abdomino-anal resection with bringing down the intestine--marginal necrosis of a xenotransplant -is summarized. The expediency of individual approach to the choice of treatment is noted. Active therapeutical tactics is suggested. PMID- 1518228 TI - [Diagnosis and therapy of acute hemorrhoids]. AB - The analysis of the results of treatment of 137 patients with acute hemorrhoids was carried out. A typical hemorrhoidal analysis was noted in 83.5% of the patients. Operated on were 129 (94.1%) patients, including 27 (20.9%)--at day 3-4 after hospitalization. Duration of hospital stay of the patients operated on after short-term preparation was 9.2 days. This figure is 4.1 days less than that in patients operated on in a delayed order. PMID- 1518229 TI - [One-stage surgery of hemorrhoids complicated with fissure in ano]. AB - The data on incidence of detection of associated rectal diseases--hemorrhoids and anal fissures--are presented. The indications for operative treatment are considered, a method suggested by the authors for surgical treatment of the mentioned diseases, which was used in 62 patients, is described. Use of the improved operative technique contributed to reduction in number of complications. Duration of treatment has shortened by 7 days. PMID- 1518230 TI - [Surgical treatment of chronic paraproctitis]. AB - The experience with operative treatment of 974 patients with chronic paraproctitis has been summarized. After the operations for intrasphincter fistula, 1% of the patients developed a disease recurrence, 0.5%--incompetence of the anal sphincter; for transsphincteric fistula--2.6 and 1.9%, respectively, for extrasphincteric fistula--5.7 and 5.2%. A fistula excision into the intestinal lumen is an operation of choice in intra- and transsphincteric fistula. In extrasphincteric fistula, fistula excision, plastic transfer of mucosa for closure of its internal opening with preservation of the anal sphincter should be performed. In presence of the extensive scars and purulent leaks, a ligature should be added to fistula excision. PMID- 1518231 TI - [Acute intestinal obstruction caused by gallstones in aged patients]. AB - The results of treatment of 6 patients operated on for acute ileus caused by a gallstone have been analysed. The authors consider the elderly and senile age not to be a contraindication for operation. PMID- 1518232 TI - [Antibiotic prophylaxis in abdominal surgery]. PMID- 1518233 TI - [Errors in diagnosis and therapy of Meckel's diverticulum]. PMID- 1518235 TI - [Intraoperative invagination of the intestine]. PMID- 1518234 TI - [Lung cancer metastasis in the vermiform process as a cause of acute destructive appendicitis]. PMID- 1518236 TI - [Purulent dermoid of the coccyx with an unusual route of pus spreading]. PMID- 1518237 TI - [A method of surgical treatment of extensive lateral abdominal hernia]. PMID- 1518238 TI - [Forceps for burying the appendiceal stump]. PMID- 1518239 TI - [A method for suturing the appendiceal stump to the peritoneum]. PMID- 1518240 TI - [A ring dilator of the anus]. PMID- 1518241 TI - [A trocar for cecoenterostomy and enterostomy]. PMID- 1518242 TI - [Surgical treatment of large and giant postoperative median abdominal hernias]. PMID- 1518243 TI - [Incarcerated hernia of the obturator foramen in an elderly female patient]. PMID- 1518244 TI - [Retrograde incarceration of the greater omentum in a direct inguinal hernia]. PMID- 1518245 TI - [Incarcerated internal paracecal hernia]. PMID- 1518246 TI - [Suppurative cyst of the vermiform process]. PMID- 1518247 TI - [Computerized tomography of the organs of the small pelvis in children with anorectal atresia]. AB - In 12 children with the different forms of anorectal atresia, for studying the state of a sphincter apparatus of the rectum and assessment of quality of its bringing down into the perineum after proctoplasty, computerized tomography of the organs of a small pelvis was used. Underdeveloped and undifferentiated musculus levator ani in children with high anorectal atresia and fistula to the urinary bladder was revealed. The method permits to establish exact location of the intestine brought down relative to musculus levator ani and external anal sphincter. PMID- 1518248 TI - [Acute appendicitis in monozygotic twins]. PMID- 1518249 TI - [Giant fibrolipoma of the small intestinal mesentery]. PMID- 1518250 TI - [Prolonged presence of a foreign body in the sigmoid colon]. PMID- 1518251 TI - [Torsion of the greater omentum]. PMID- 1518252 TI - [Simultaneous operations in elderly patients]. PMID- 1518253 TI - [Intestinal obstruction as a complication of distal ileitis]. PMID- 1518254 TI - [Acute intestinal obstruction in a patient with an aberrant pancreas]. PMID- 1518255 TI - [Myelodysplastic diseases in childhood]. AB - The myelodysplastic syndromes (MDS) are a group of hematopoietic neoplasms characterized by ineffective hematopoiesis and a high risk of transformation in acute leukemia. Pathogenesis and clinical course of these disorders are heterogenous. MDS is unusual in childhood, and differential diagnosis is specially broad in this age group. Allogenic bone marrow transplantation is the treatment of choice. Therapy with hematopoietic growth factors can overcome the maturation defect of the malignant clone in some instances. Multicenter studies are necessary to accumulate sufficient data on pathogenesis, clinical course and treatment results of MDS in childhood. PMID- 1518256 TI - [Is the pharmacokinetic profile of cytarabine clinically relevant?]. AB - Cytarabine (Ara-C) is a cytotoxic agent which is rapidly metabolized and thus has a short half-life. Consequently, variations of infusion time influence directly the plasma level over time. Individual differences in plasma level courses with identical dosage are irrelevant regarding treatment response. Several studies, however, reported correlation of the leukemic cells' ability to build and retain the metabolite Ara-C-triphosphate (Ara-CTP) intracellularly with clinical response to therapy. The half-life of the intracellular Ara-CTP concentration in myelogenic blasts (AML) is lower than in blasts from children with acute lymphoblastic leukemia (common-ALL). The varying dosage recommendations of conventional (CD), intermediate (ID) and high-dose (HD) Ara-C therapy are based on considerations of cellular pharmacology. ID and HD Ara-C therapy schedules are designed to overcome well-known resistance phenomena thus providing high intracellular Ara-CTP concentrations. PMID- 1518257 TI - [Experiences with modified BFM protocols in the treatment of children with acute lymphoblastic leukemia (ALL) in East Germany 1981-1991]. AB - Between September and August 1991 818 previously untreated children and adolescents up to 18 years of age with acute lymphoblastic leukemia were entered into two modified BFM-protocols. Patients with B-ALL were excluded. From 1981 to 1987 524 patients were entered into the randomized multicenter study ALL VII/81 (modified ALL-BFM 81 protocol). Patients were divided into three risk groups standard (SR), medium (MR), high risk (HR) using the BFM risk factor. In a connecting study from 1988 to 1991 294 patients were registered on the stratified and randomized multicentric trial ALL VIII/87 (modified ALL-BFM 86 study). The main modification in study ALL VII/81 concerned the duration of treatment. Patients were randomized into two groups. The first group received as a late reinduction protocol III and then therapy was stopped. The second group received 6-MP and MTX for another six months. The other whole treatment strategy of ALL BFM 81 was adopted. In protocol ALL VIII/87 the only modification was the reduction of the MTX dosage from 5 g/m2 to 1 g/m2 with an infusion time of 24 hours (leucovorin rescue 15 mg/m2 after 48 and 54 hours). The probability of the event-free-survival (EFS) for study ALL VII/81 was 59%. CNS events were significantly more frequent in standard risk patients with intermediate dose MTX (4 x 0.5 g/m2) compared with the irradiation group (18 Gy). The EFS for SR patients amounts to 61%, for MR patients to 59% and for HR patients to 36%. There was no significant difference of EFS for the two groups with different duration of therapy.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1518258 TI - [Effect of dose intensity and therapy-induced leukocytopenia in intensive therapy on the prognosis of acute lymphatic leukemia in childhood. Results in 213 patients of the COALL-85 study]. AB - Dose intensity (DI) plays an important role in the treatment of neoplastic diseases. The individual DI within a protocol may vary considerably and thus may be an important prognostic factor. In 213/305 patients treated in the cooperative study COALL-85 for childhood acute lymphoblastic leukemia the following parameters of individual therapy intensity were analyzed: Total time for intensive treatment, cumulative doses of single drugs, mean relative dose (= relation between received and prescribed doses of all drugs), mean relative dose intensity ( = mean relative dose/time) as well as frequency and duration of leukocytopenia. Therapy for LR (low-risk) and HR (high-risk) patients were separately analyzed by both life-table method and multivariate regression analysis. Neither length of time, mean relative dose intensity nor the other parameters had any significant influence on prognosis within the HR protocol. The only significant prognostic factor was the remission status on day 28 (p less than 0.001 in multivariate analysis). In contrast patients treated with the LR protocol had significantly fewer relapses if treatment resulted in leukocytopenic episodes (probability for event free survival (EFS) = 0.76 in patients with one or two leukocytopenic episodes compared to 0.52 in patients with none). Patients with a mean relative dose greater than 0.9 showed a higher EFS of borderline significance than patients with mean relative dose less than = 0.9 (0.72 vs 0.49, p = 0.09). We would like to conclude, that treatment protocols with very intensive and prolonged combination chemotherapy have a certain margin of safety in DI without disadvantage for the patient.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1518259 TI - [Effect of cranial irradiation on rate of recurrence in children with acute myeloid leukemia. Initial results of the AML-BFM-87 study. The AML-BFM Study Group]. AB - Study AML-BFM-87 compared prospectively if cranial irradiation could be abandoned by adding two blocks of intensification with high dose ARA-C and VP-16 after consolidation and furthermore, improve prognosis compared to study -83. 210 children were enrolled in study AML-BFM-87 until March 31, 1991. 164 (78%) achieved complete remission. Probabilities for event-free survival (EFS) and event-free interval (EFI) of 5 years were: .45 (SD .04) and .57 (SD .05). In the first 2.5 years of the study irradiation was randomized (n = 31), selected or refused (n = 24). However, during this period irradiation was mandatory in patients with leukocyte count greater than 70,000/mm3, and also in children with initial CNS involvement. Since July 1989 prophylactic cranial irradiation was abandoned. Patients of the group with mandatory irradiation (n = 39) presented with more unfavourable risk parameters than the group of non-irradiated children, who were enrolled in the study after randomisation had been stopped. Nevertheless, results showed in randomized and selected patient groups as well as in the total cohort a longer relapse-free interval (RFI) in irradiated (n = 66) compared to non-irradiated (n = 94) patients (RFI of 5 years: .70, SD .04 vs. .51, SD .07, p less than .05). Relapses in non-irradiated children occurred mainly in the bone marrow and less often in the CNS. The increase in relapse rate was seen especially in non-irradiated patients of the low risk group as defined in study AML-BFM-83 (RFI: .40, SD .14 vs. .79, SD .09 with irradiation, p less than .01). In the high risk group, however, the differences were not significant. Our results suggest that cranial irradiation is an important part of therapy in childhood AML, and that the good prognosis of the low risk group in study AML-BFM 83 was probably based on the combination of intensive chemotherapy and cranial irradiation. PMID- 1518260 TI - [Comparison of chemotherapy alone with allogeneic bone marrow transplantation in first full remission in children with acute myeloid leukemia in the AML-BFM-83 and AML-BFM-87 studies--matched pair analysis]. AB - 16 patients of studies AML-BFM-83 and -87 with allogeneic bone marrow transplantation (BMT) in first complete remission (CR) were compared with matched controls with postremission chemotherapy (CT-MC). CT-MC were selected from 250 non-grafted patients with a minimum of remission duration corresponding to the median interval between remission and allogeneic BMT (7.3 and 3.6 months in studies BFM-83 and BFM-87). Matched pair criteria according to prognostic significance were: blast cell reduction day 15 in bone marrow, FAB subtypes, white blood cell count, age, and time to CR. Therapy results in BMT and CT-MC groups were comparable: 2 relapses and 2 treatment-related deaths after BMT vs. 5 relapses. The probability for event-free interval of 9 years was: .73 (SD .12) in the BMT group vs. .67 (SD .12) in the CT-MC group. Early and late toxicity was higher in the BMT group. 3 children of the BMT group had tolerable or severe sequelae (convulsive seizures, hemiparesis). Currently, there is no advantage for allogeneic BMT in first CR according to our results. Only high risk patients should be grafted as soon as possible after achieving CR. PMID- 1518261 TI - [Treatment of recurrence of acute myeloid leukemia in childhood. A retrospective analysis of recurrence in the AML-BFM-83 study]. AB - Complete remission (CR) rates of 80% are achieved with the AML-BFM protocols but one third of patients relapse within the first three years. There are few reports of treatment of relapsed childhood AML, and these deal with the evaluation of new drugs for frontline therapy. We performed a retrospective analysis to investigate how patients previously treated with the AML-BFM-83 protocol were treated after relapse and how many long term remissions were achieved. 48 of 139 patients relapsed after having achieved complete remission with the AML-BFM-83 protocol which consists of continous infusion of ARA-C 100 mg/m2 day 1-2, ARA-C 200 mg/m2 day 3-8, Daunorubicin 60 mg/m2 day 3, 4, and 5, and VP-16 150 mg/m2 day 6, 7, and 8, and an 8 week consolidation therapy consisting of Prednisolone, Thioguanine, Vincristine, ADR, ARA-C, Cyclophosphamide, intrathecal ARA-C and cranial irradiation followed by maintenance therapy. Duration of first remission ranged from 1.5 months to 66.3 months. Excluding 5 children with either isolated or combined extramedullary relapses and another 4 patients for missing data, 39 children were evaluable. 20 children received no therapy or palliative therapy while 16 patients received chemotherapy and another 3 children were transplanted in relapse. Although 9 different intensive chemotherapy regimens were used for reinduction, a high number (12 of 16 = 75%) of second complete remissions was achieved. Several therapeutic options were used to maintain a second remission: regular maintenance therapy (7 patients), allogeneous bone marrow transplantation (BMT) (2 patients), autologous BMT (3 patients).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1518262 TI - [German multicenter thalassemia study. Concept and initial results]. AB - At present more than 300 children and adolescents with Thalassaemia major are living in the FRG. The purpose of this project is--for the first time--to apply a standardized therapy protocol to these patients, to prove its effectivity and study side-effects. The multi-center study started in April 1991. The therapy is based on periodical transfusion of erythrocytes in order to keep haemoglobin (Hb) concentration (= basic Hb-value) above 10.5 g/dl, and daily application of Desferal, 40 mg/kg bw s.c. for iron elimination. Until Nov. 30, 1991 74 patients from 31 different childrens hospitals entered the study. Preliminary results after evaluation of the basic questionnaires can be summarized as follows: 1. The majority of patients if not too old to highly profit from improvement of therapy; 2. In 40.9% of these patients HbF concentration was higher than 15%, which indicates a suboptimal transfusion therapy; 3. At least 30% of patients need intensified iron elimination. Even these preliminary data demonstrate the necessity to improve the therapy of Thalassaemia major in Germany. The goal is to include all affected patients in the study and so optimize long term results concerning quality of life and prognosis. PMID- 1518263 TI - [Changes in blood coagulation in treatment with ALL-BFM-90 and NHL-BFM-90 protocols]. AB - 1. Treatment according to the ALL/NHL-BFM 90 protocol I (induction phase) caused multiple and severe coagulation changes in all 14 patients of our study. Glucocorticoids alone made Fibrinogen drop to 148 mg/dl, AT III and Protein C rise to 136% or even 179% respectively. After day 12, immediately following the start of therapy with Coli-Asparaginase (ASP), fibrinogen continued to drop to reach its lowest average value of 46 mg/dl on day 24. Anticoagulant factors like plasminogen (lowest average value: 36%), AT III (47%) and Protein C (93%) dropped abruptly. These alterations were reversed after discontinuation of Glucocorticoids and ASP. During consolidation (protocol II) similar alterations are observed as in protocol I when Glucocorticoids are applied alone. However, after Erwinia-ASP there is no fall in AT III, plasminogen, and Protein C as is observed in protocol I with Coli-ASP. 2. Severe hemorrhages or thromboses are uncommon as compared to the degree of coagulation changes which can be regularly observed. Complications occur more often in girls. Most of them are seen during the 2nd or 3rd week of simultaneous ASP-Glucocorticoid therapy. 3. To avoid twofold alteration of hemostasis it should be considered to apply Glucocorticoids and ASP separately and to replace Coli-ASP by Erwinia-ASP. The efficacy of prophylactic replacement of decreased coagulation factors has not yet been confirmed. Immunologic and infectious side effects have to be taken into consideration. 4. More definite recommendations can be given when each suspected bleeding and/or thrombosis is confirmed by imaging procedures, when it is documented and registered, and when coagulation studies are performed during the critical phase. PMID- 1518264 TI - [Clinical experiences with adrenaline as therapy and prevention of E. coli-L asparaginase-induced anaphylaxis]. AB - Management of E.-coli L-asparaginase induced anaphylaxis mainly consists of application of i.v. epinephrine but also in the withdrawal of this drug. Despite of this firm recommendation we have shown in 7 patients with E. coli L asparaginase induced anaphylaxis, that further application of the drug is possible in the presence of a continuous epinephrine infusion (0.01-0.02 mg/kg) started one hour before and finished one hour after the concomittant infusion of the E.-coli L-asparaginase. In none of the patients there was a second event of anaphylaxis even though most of the patients still had to continue on E.-coli L asparaginase with an average of more than 6 infusion. PMID- 1518265 TI - [The IgG subclass level in children and adolescents with malignant diseases]. AB - Children with malignant disease have an increased risk for bacterial infections. We investigated a possible correlation between septic episodes and decreased IgG subclass levels in 63 patients. At diagnosis 13 of 50 children showed decreased IgG subclass levels: 10x IgG4, 2x IgG1, and 1x IgG3 + IgG4 were reduced. Bone marrow infiltration by tumor cells did not increase the frequency of subclass reductions (4/25 with, 9/25 without bone marrow infiltration). The time course of subclass levels was followed during 37 febrile episodes (mainly fever of unknown origin, septicemia, pneumonia) of 23 children under cytostatic therapy. 6 patients showed transient low IgG subclasses: 2x IgG4, 1x IgG1, 1x IgG3, 1x IgG2 + IgG4, and 1x IgG1 + IgG3 + IgG4. Children with decreased IgG subclass levels appeared to occur more independently of leucopenia. In general, febrile episodes in children with subclass decreases did not last a longer period and did not occur more frequently than in children without IgG subclass deficiencies. In conclusion, the determination of IgG subclasses in cancer children at diagnosis or during chemotherapy did not add substantial information of prognostic or therapeutic relevance. PMID- 1518266 TI - [Early neuroblastoma detection in Germany. On the status of the Hamburg-Stuttgart cooperative pilot study]. AB - In Germany, a pilot study for the early detection of neuroblastoma was initiated at the beginning of 1991 in the regions of Hamburg and Stuttgart. The aims of the study are: (1) to develop an infrastructure for neuroblastoma screening, (2) to test the methodology, (3) to determine the compliance rate, (4) to collect data for a future epidemiological study. At 6 months of age, the parents are contacted by general practitioners and private pediatricians within the framework of the routine infant surveillance. The parents are informed about the pilot study and given a sampling kit. A simple urine sample is required, which is collected on a test strip, dried and sent to the test center. From the eluate, the levels of Vanillymandelic acid (VMA) and Homovanillic acid (HVA) are estimated by high performance liquid chromatography (HPLC). The results are sent to the practitioner. In cases of insufficient samples or raised values, the parents are asked for a second sample. If a raised value is comfirmed, clinical investigation including abdominal ultrasound and chest X-ray is carried out. From 2-12/1991, 27,282 samples were examined. There were 1326 (4.86%) insufficient samples and 644 (2.36%) samples retested because of raised initial VMA/HVA levels. 45 (0.15%) children were clinically examined. Until now 2 of them have still elevated levels without evidence of tumor and 2 others have evidence of a tumor which has not been proven to be neuroblastoma. These first results are encouraging with respect to the feasibility of carrying out a neuroblastoma screening program in Germany. It is to early to assess the compliance rate. PMID- 1518267 TI - [The "Lower Saxony/Northern Rhine-Westphalia" Neuroblastoma Screening Project: on the need for epidemiologic comparison]. AB - The proof for the general evolution of metastatic neuroblastoma from localized disease by a low-speed process is lacking. The epidemiological approach would require the decrease of neuroblastoma related mortality by reduction of the number of metastatic cases per population unit as a result of a screening program. During 1983 through 1990 the neuroblastoma incidence in the FRG was 0.85 1.09 cases per 100,000 children less than 15 years of age. The mortality rate ranged between 0.25 and 0.49 deaths per 100,000 children. The project "Niedersachsen/Nordrhein-Westfalen" started April 1st, 1992 and is investigating urinary catecholamine metabolite excretion in infants at the age of 10-12 months and for a second time in toddlers at 17-19 months. The target population includes 24.7 million inhabitants with 267,000 births per year. The urine sampled on filter paper is analyzed using thin layer chromatography. Positive and questionable positive results are confirmed by HPLC and GC-MS. The aim of the study is to demonstrate the feasibility of the chosen approach. Furthermore first epidemiological data will be obtained. Until a population-based study on neuroblastoma mortality in screened versus controlled populations has proven the usefulness of the screening it cannot be recommended as a general service to the public. PMID- 1518268 TI - Cell-kinetics and biochemical pharmacology of methotrexate and 6-mercaptopurine in human malignant T-lymphoblasts. AB - The cell-kinetics and biochemical pharmacology of simultaneous and sequential combination treatment with 0.02 microM methotrexate (MTX) and 2 microM 6 mercaptopurine (6MP) were studied in MOLT-4 malignant T-lymphoblasts. The results were compared with our data from earlier studies of separate treatment with these antimetabolites. A synergistic effect of combination treatment could be demonstrated, based on the inhibition of purine de novo synthesis by both agents, on DNA and RNA synthesis, on the incorporation of 6-thioguanine nucleotides into DNA and RNA, and on inhibition of cell growth and clonal growth. The synergistic effects of combination treatment with MTX and 6MP will only be available in malignant lymphoblasts, and will be absent in normal bone marrow cells and normal lymphocytes, because the activity of purine de novo synthesis in these cells is absent or low. Based on the synergistic effects of MTX and 6MP and the good penetration of both agents in the cerebrospinal fluid, the Dutch Childhood Leukemia Study Group presently performs a randomized study during protocol M of the BFM/DCLSG-ALL-90 protocol comparing the results of 4 times each two weeks 24 hr intravenous administration of MTX (5 g/m2) versus intravenous MTX, immediately followed by 24 hr intravenous administration of 6MP (1.3 g/m2). The pharmacokinetics and intracellular biochemical pharmacology of 6MP in lymphocytes will be studied, comparing intravenous administration and low dose oral administration. PMID- 1518269 TI - [Ifosfamide and the metabolites of side chain oxidation--excretion in urine in various pediatric therapeutic protocols]. AB - The precondition for the antineoplastic effect of ifosfamide (Ifo) is the oxydation of the oxazaphosphorine ring system. The 'ring oxidation' by several steps leads to the formation of alkylating mustard. A second metabolic pathway results in the cytostatically inactive metabolites 2- and 3-deschlorethyl ifosfamide (2-, and 3-d-Ifo). This 'side chain oxidation' plays a quantitatively more important role with ifosfamide than with cyclophosphamide. The urinary excretion of unmetabolized Ifo and of 2- and 3-d-Ifo, which represents the amount of Ifo not activated, has been investigated by capillary gaschromatography in 18 treatment cycles of 14 children with various therapeutic schedules (800, 2000 and 3000 mg/m2 given as bolus, over 1 h or as continuous infusion for 2 respectively 5 days). The total cumulative excretion during 12 completely sampled cycles ranged from 27 to 50% of the given Ifo. Between 14 and 34% could be detected as IFO, 9 to 29% as 3-d-Ifo and 2 to 8% as 2-d-Ifo. In 4 children the amount of 'side chain oxidized' IFO exceeded the amount of unmetabolized Ifo. 24 hours after the end of therapy excretion is nearly complete. No relationship between the excreted amount of unmetabolized Ifo, 2-d-Ifo and 3-d-Ifo and the dose schedule could be determined. There was no clearcut dependency between cumulative dose, the children got in the past, and formation of 2- and 3-d-metabolites. PMID- 1518270 TI - Thyroid function in premature infants. AB - The present study was performed using the simultaneous assays of free T4 and TSH levels in dried blood spots of filter paper for mass-screening of inborn errors of metabolism in order to clarify the thyroid function of premature infants. The subjects were divided in three groups: A group infants less than 1500 g at birth (n = 34, 27.4 +/- 2.6 weeks of gestational age), B group infants from 1500 to 2500 g at birth (n = 104, 35.6 +/- 2.4 weeks) and C group infants over 2500 g at birth (n = 490, 39.0 +/- 1.2 weeks). TSH levels were 4.51 +/- 3.03, 2.62 +/- 2.24 and 2.84 +/- 2.06 microU/ml in A, B and C group respectively and significant difference was recognized in group A and C. Free T4 levels were 0.71 +/- 0.42, 1.81 +/- 0.96 and 2.15 +/- 0.67 ng/dl, in group A, B and C respectively, and significant differences were recognized in all three groups. There was positive correlation between free T4 levels and gestational ages (Y = -2.413 +/- 0.11725X, r = 0.206, p less than 0.05). PMID- 1518271 TI - A novel type of regulatory protein for the GDP/GTP exchange reaction of rho p21, a ras p21-like small GTP-binding protein, in rabbit intestine. AB - A novel regulatory protein for rho p21, a ras p21-like GTP-binding protein (G protein), was purified from the cytosol fraction of rabbit intestine. This protein, designated as rho GDP dissociation inhibitor (GDI), regulated the GDP/GTP exchange reaction of rho p21 by inhibiting the dissociation of GDP from and subsequent binding of GTP to it. rho GDI did not affect the GTPase activity of rho p21. rho GDI formed a complex with the GDP-bound form of rho p21 but not the GTP-bound form. rho GDI was inactive for other small G proteins including ras p21, smg p21 and smg p25A. These results indicate that rho GDI is a novel type of regulatory protein for the GDP/GTP exchange reaction of rho p21. PMID- 1518272 TI - Long-term preservation of canine pancreas by a new simple cold storage method using perfluorochemical--the two-layer cold storage method (Euro-Collins' solution/perfluorochemical). AB - Long term preservation of canine pancreas by a new simple cold storage method using perfluorochemical (PFC), two-layer (Euro-Collins' solution (EC)/PFC) cold storage method, was tested in the canine model of segmental pancreas autotransplantation. The functional recovery of the graft preserved by this method (group 1) was determined by daily fasting blood glucose concentration and intravenous glucose tolerance test at two weeks after autotransplantation and compared with simple cold storage with EC (group 2), cold storage in EC with simple bubbling of oxygen (group 3), and control (no preservation) (group 4). Maintenance of normoglycemia at least 5 days after transplantation was considered a success of preservation. The functional success rates after 24 hour preservation were 4/4 (100%), 4/4 (100%) and 4/5 (80%) for groups 1, 2 and 3 respectively, and the functional success rates of groups 1, 2 and 3 after 48 hour preservation were 5/6 (86%), 1/5 (20%) and 1/5 (20%) respectively. In addition the functional success rates after 72 hour preservation were 6/6 (100%), 0/6 (0%) and 0/5 (0%) for groups 1, 2, and 3 respectively. It was clear that the two-layer cold storage method had made it possible to preserve the canine pancreas for up to 72 hours although the upper limit of reliable preservation time of groups 2 and 3 was 24 hours. The mean K value of group 1 after 72 hour preservation was 1.78 +/- 0.42 compared with 2.05 +/- 0.32 of group 4 at two weeks after transplantation. Biopsies of grafts of group 2 and 3 after 72 hours preservation showed remarkable autolytic changes in exocrine and endocrine tissues. In contrast, biopsies of grafts of group 1 after 72 hour preservation showed almost normal architecture in both tissues. In addition, biopsies of 72 hour preserved grafts of group 1 at 4 weeks after autotransplantation showed almost normal pancreatic architecture with minimal fibrotic changes in the exocrine tissue. This study demonstrated the possibility of long-term preservation of the pancreas for transplantation. PMID- 1518274 TI - Weakness of thigh muscles in individuals sustaining anterior cruciate ligament injury. AB - The purpose of this study was to assess the quadriceps and hamstrings muscle strength deficits at different knee flexion angles (30 degrees and 60 degrees) in individuals who had sustained anterior cruciate ligament (ACL) injury, who had never had thigh muscle strengthening exercise. Isometric (0 degree/sec) and isokinetic (60 degrees/sec and 180 degrees/sec) torque measurements were performed on sixty-six patients (29 males and 37 females) with chronic ACL insufficiency. Significant strength deficits of the quadriceps and hamstrings muscles in injured knees were found at both 30 degrees and 60 degrees of knee flexion in three testing conditions (0 degree/sec, 60 degrees/sec, and 180 degrees/sec). In the comparison of torque production at 30 degrees and 60 degrees knee flexion angles, for the male group, significantly greater deficits of the quadriceps torque were found at 60 degrees knee flexion than at 30 degrees knee flexion in the isometric and isokinetic 60 degrees/sec testing modes. For the female group, significantly greater deficit of the quadriceps torque was found at 60 degrees knee flexion than at 30 degrees knee flexion only in isokinetic 60 degrees/sec. There was no significant difference of the hamstrings torque deficit between 30 degrees and 60 degrees knee flexion in any testing modes. In the comparison of isometric and two isokinetic testing modes (60 degrees/sec and 180 degrees/sec), for the male group, significantly greater deficits of the quadriceps torque were found at 30 degrees knee flexion in isokinetic 180 degrees/sec and at 60 degrees knee flexion in isokinetic 60 degrees/sec as compared to the isometric test. There was no statistical difference in the hamstrings torque values. For the female group, significantly greater deficits of the quadriceps and hamstrings torque were found at 30 degrees knee flexion in isokinetic 60 degrees/sec and at 60 degrees in isokinetic 60 degrees/sec and 180 degrees/sec as compared to the isometric test. It was concluded that long lasting instability without any muscle exercises may result in the weakness of not only the quadriceps muscle but also even hamstrings muscle, and that the quadriceps strength might be more susceptible to ACL insufficiency at 60 degrees knee flexion angle than at 30 degrees knee flexion angle, whereas, the hamstrings did not show any angular-specific torque deficits. These findings might resulted from characteristics of torque-curves of the quadriceps and hamstrings muscles.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1518273 TI - Function of the post-translationally modified C-terminal region of rho p21. AB - rhoA p21, a ras p21-like small GTP-binding protein, purified from bovine aortic smooth muscle is similarly modified at its C-terminal region as described for ras p21s. In this study, I examined the role of the post-translational modifications of the C-terminal region of rhoA p21 by comparing bovine rhoA p21 with bacterially-produced rhoA p21 because the bacterial protein was not modified. Bovine rhoA p21 bound to plasma membranes, but bacterial rhoA p21 did not. Both the stimulatory and inhibitory GDP/GTP exchange proteins for bovine rhoA p21 were inactive for bacterial rhoA p21. On the other hand, the GTPase activating protein for bovine rhoA p21 was also active for bacterial rhoA p21. These results indicate that the post-translational modifications of the C-terminal region of bovine rhoA p21, which are absent in bacterial rhoA p21, are essential for its interaction with membranes and the stimulatory and inhibitory GDP/GTP exchange proteins but not with the GTPase activating protein. PMID- 1518275 TI - Chest roentgenographic techniques for demonstrating human lung tumour xenografts in nude rats. AB - Roentgenographic techniques were investigated for imaging orthotopic lung tumours in anaesthetized nude rats endobronchially implanted with human lung cancer cells. A conventional radiographic unit with a dual-screen, double-emulsion film mammographic receptor produced images preferable to those from a mammographic unit because of superior resolution. Typical exposure factors were 300 mA, 29 kVp, and 17 ms at a focus-film distance of 76 cm with a 2.11 by 2.41 mm effective focal spot and inherent filtration of 1.2 mm aluminium. Sensitivity for tumour detection was 0.93 for 59 animals with pathologically proved tumours and 0.96 for 54 animals with tumours larger than 4 mm or 50 mg. For 24 pathologically tumour free animals, specificity was 1.00. For 55 animals radiographically judged to have tumours, positive predictive value was 1.00. For all 83 animals, accuracy was 0.95. This technique effectively demonstrates orthotopic human lung tumours in nude rats and should be useful for noninvasive monitoring of tumour presence, location, size, and changes in size. PMID- 1518276 TI - Effects of urethane, alphaxolone/alphadolone, or halothane with or without neuromuscular blockade on survival during repeated episodes of global cerebral ischaemia in the rat. AB - The effect of 4 anaesthetic regimens on blood pressure and survival was investigated during repeated episodes of cerebral ischaemia in the rat induced by diathermy of the vertebral arteries and reversible occlusion of the carotid arteries. The best results were obtained with inspired halothane with neuromuscular blockade and artificial ventilation, followed in order by halothane, intravenous alphaxolone/alphadolone, and intraperitoneal urethane with spontaneous ventilation. PMID- 1518277 TI - Euonymus europaeus lectin as an endothelial and epithelial marker in canine tissues. AB - The Euonymus europaeus agglutinin (EEA) is an endothelial marker in mammalia. In canine tissues, 4 types of endothelial cells (general, nervous, arterial, hepatic) were identified by the presence of the EEA receptor and by its sensitivity to neuraminidase enhancement. In adult dogs, EEA binding saccharides had endothelial or epithelial distributions and reactivities similar to those described for human tissues. Different EEA reactivities were observed between fetal, neonatal and adult canine tissues mainly at the arterial level. These findings suggest that the development of the binding sites is not identical in dog and man. Related lectins and monoclonal antibodies were used to characterize the EEA binding site, and the probable structure of the EEA binding saccharide in endothelial cells appeared to be alpha Gal (1,3) beta Gal (1,4) GlcNAc. PMID- 1518278 TI - A method for hyperthermic treatment of mouse skin. AB - The Sencar mouse skin system is a recognized model for tumour initiation, promotion and progression. The current interest in the effect of hyperthermia on this multi-stage tumorigenesis model prompted the need for a technique to accurately heat a section of dorsal skin of a large number of mice for 30 min per heat treatment. In the technique described, experimental groups of 25 female Sencar mice were treated at 7-8 weeks of age under general methoxyflurane anaesthesia. Treatment consisted of the application of initiating and/or promoting agents with or without hyperthermia. For hyperthermic skin treatments, each group of mice was placed onto a platform in a water bath so that the dorsal skin of the mice was in contact with 44 degrees C temperature controlled water. PMID- 1518279 TI - The lipid composition of milk from mice fed high or low fat diets. AB - Total fatty acids and the proportions of methyl esters of individual fatty acids were measured in mouse milk. Pregnant mice were fed either a high fat (HF) diet or a low fat (LF) diet from 14 days of gestation. After parturition, each dam was milked once a day for a period of 18 days. The mean total fatty acid concentration over the entire study period was 110 mg/g of milk (approximately 11.7% fat as triglyceride) for both dietary treatment groups. During days 2 to 6 postpartum, the mean total fatty acid concentration for dams fed HF diet was lower than for the LF group. Although the concentration of total fatty acids of mouse milk was not affected by the level of dietary fat fed to the dam, several variations in the proportions of individual fatty acids were observed. PMID- 1518280 TI - Monitoring of blood gas parameters and acid-base balance of pregnant and non pregnant rabbits (Oryctolagus cuniculus) in routine experimental conditions. AB - Blood gas parameters and acid-base balance values were determined in adult pregnant New Zealand rabbits (Oryctolagus cuniculus) in standard laboratory housing conditions and during anaesthesia with an association of ketamine chlorpromazine, administered before surgical procedures. All the variables were also studied in adult non-pregnant female, used as controls. No differences in pH, sO2c, O2Hb, COHb, sO2m and a-vDO2 were found between pregnant and non pregnant rabbits in physiological conditions and during anaesthesia. Ketamine chlorpromazine and pregnancy seemed to change the other parameters used to assess the acid-base balance and the oxygenation conditions. Anaesthesia affected only Hb, O2Ct, O2Cap, CcO2 and P50. The additive effect of pregnancy and anaesthesia modified pCO2, pO2, HCO3-, TCO2, BEb, SBC, BEecf, A-aDO2, RI, MetHb, RHb, CaO2 and CvO2. The patterns described are close to those of other species, suggesting the New Zealand rabbit might be a reliable animal model for monitoring selected variables. PMID- 1518281 TI - Spontaneous inclusion body hepatitis in young tamarins: I. Morphological study. AB - Over a period of 4 years approximately 60% of the new born and juvenile animals in a breeding colony of tamarins (Saguinus fuscicollis) died a sudden death. Histological examination at necropsy revealed interstitial hepatitis in 22 of the 30 young animals of the present study. The hepatocytes contained intranuclear inclusion bodies in 12 of the 22 cases. Upon ultrastructural examination, tubulovesicular structures and amorphous material were found in the nuclei. The endoplasmic reticulum had proliferated and was closely associated with undulating curved membranes. These morphological alterations resemble those reported in chimpanzees experimentally infected with NANB hepatitis viruses. PMID- 1518282 TI - Sex ratio and mortality in a laboratory colony of the common marmoset (Callithrix jacchus). AB - In a retrospective study sex ratio and mortality were analysed in a captive colony of common marmosets (Callithrix jacchus). Seven hundred and thirty-five infants in 294 litters (20 singletons, 119 twins, 140 triplets, 14 quadruplets) out of 57 breeding females were evaluated. The sex ratio at birth was 0.95 males:1.0 females. The frequency of males and females, as well as the sex composition of twins and triplets confirm the assumption of dizygotic twinning in the common marmoset. According to age at death, 9 categories were differentiated, with perinatal mortality being the highest. Once early infancy had passed the probability of a common marmoset infant of our colony reaching childhood is nearly 95%. Sixty per cent of all liveborn infants survived beyond 18 months. Mortality of infants at birth from primiparous mothers did not differ from that of pluriparous females, nor did the survival rate of infants with the filial generation the respective female had reached (F1 to F6). Females with a high ratio of triplets and quadruplets had a lower reproductive success than females with a majority of singleton or twin deliveries. Differential mortality between males and females was not observed. The frequency of stillbirths was not strongly related to parity, but was to litter-size. Most stillborn babies were seen in sets of quadruplets, most abortions in singletons. A normal socialization in a stable social environment, as well as not pairing the animals before they are fully adult, are considered important factors in good breeding success and infant survival. PMID- 1518283 TI - Recent clues to the pathogenesis of spondyloarthropathies. PMID- 1518284 TI - Epidemiology of Rocky Mountain spotted fever in South Carolina, 1985-1990. AB - By analyzing three different sources of data including DHEC reported cases, hospital discharge data, and death certificates, our study reveals that RMSF is endemic in South Carolina particularly in the Piedmont area and that underreporting of RMSF in South Carolina is likely. The incidence and case fatality rates of RMSF derived from hospital discharge data are higher than these rates derived from cases reported to DHEC. Physicians should be aware of the endemicity of RMSF in South Carolina and should include it in the differential diagnosis of any case of fever of unknown origin especially during the spring and summer seasons regardless of the history of a tick bite. PMID- 1518285 TI - Managing agitation in the critical care setting. AB - Pharmacologic control of the agitated ICU patient requires preliminary assessment of the underlying causes of agitation. Reversal of correctable abnormalities, consideration of drug reaction, withdrawal and pain management should be addressed first. Delirium is the most common cause of agitation in the ICU and often has multiple causes. Pharmacologic management of agitation can be safely accomplished by intravenous haloperidol with or without lorazepam, as outlined above. PMID- 1518286 TI - Grass always looks greener on the other side. PMID- 1518287 TI - Research, patient care and the practicing physician. PMID- 1518288 TI - Prophylactic lymph node dissection for malignant melanoma: what to do while we wait. PMID- 1518289 TI - Heterogeneity in gastric carcinoma with special reference to DNA content and mitotic activity: histopathologic differentiation. AB - DNA ploidy and mitotic activity were microspectrophotometrically investigated in 46 patients with gastric carcinoma. Measurements of DNA content and mitotic index (M.I.) were examined in the mucosal, submucosal, muscularis propria, and serosal layers of tumors, respectively. The frequency of cells with values exceeding hexaploid chromosome (6c) and mitotic counting analysis revealed a significant higher value in serosa, compared with findings in the mucosa. This tendency was not evident in cases of a differentiated type adenocarcinoma but was noted in those with the undifferentiated type. There were 37 tumors (80.0%) with the same DNA distribution patterns in every layer of the stomach (homogeneous DNA ploidy). Heterogeneity of DNA ploidy was observed in nine tumors (20.0%). Carcinoma with a heterogeneous DNA ploidy manifested a significantly higher incidence of metastasis to the lymph nodes than did those with homogeneous type. Characteristically, there was venous permeation preponderance in the differentiated type and peritoneal dissemination preponderance in the undifferentiated type. This evidence of DNA heterogeneity in gastric carcinoma tissues suggests a possible correlation with the metastatic behavior. PMID- 1518290 TI - Atrophic chronic gastritis and esophagogastric anastomotic leak after resection and reconstruction for esophageal carcinoma. AB - The incidence of anastomotic leakage after esophagectomy for cancer and reconstruction with the stomach was analyzed with respect to the presence of coexistent atrophic chronic gastritis (ACG). Of a total of 28 operated esophageal cancer patients with ACG, 6 patients developed an anastomotic leak at the cervical esophagogastrostomy (21%). Of a total of 8 operated esophageal cancer patients none of the patients developed an anastomotic leak. The ACG positive and the ACG negative patients were found to be well matched for age, sex, type of operation, transplant route, level of the anastomoses, and suture technique, and all were operated on by the same surgeons. The difference in leakage rate did not reach statistical significance. PMID- 1518291 TI - Flow cytometric DNA analysis of hepatic tumours on ultrasound-guided fine-needle aspirates. AB - A study was performed on a nonconsecutive series of 51 patients in order to assess the feasibility, reliability, and usefulness of flow cytometric (FCM) DNA analysis of samples obtained from benign and malignant hepatic tumours by means of ultrasound-guided fine-needle aspiration (UG-FNA). Cytological and often histological confirmation of the nature of the lesion was obtained in all cases from an expert pathologist. For FCM DNA analysis in 32 cases, it was also possible to use samples obtained at surgery from the actual tumours. There were no post UG-FNA complications, either early or late. It was possible to perform FCM DNA analysis on 6/7 (85.7%) of the benign tumour aspirates and all 44 (100%) coming from the malignant tumours. All the benign tumours showed a DNA-diploid pattern, while the DNA content was aneuploid in 91% of the malignant tumours. Apart from one case, the results of the FCM DNA analysis of the samples removed at surgery were the same as those obtained from the aspirates (97%). FCM DNA analysis on UG-FNA samples from hepatic tumours is a fairly simple, reproducible, well-tolerated technique; it does not involve risks if performed by skilled operators and, since it can be easily repeated even on small tumours, it is a suitable method for monitoring hepatic metastases during chemotherapy. PMID- 1518292 TI - Effect of liposomal interleukin-2 on ascites-forming rat hepatoma. AB - Interleukin-2 was entrapped in liposomes (Lip-IL-2) and injected into rats. The intraperitoneal injection of Lip-IL-2 into rats bearing an ascites-forming rat hepatoma (AH-66) significantly increased the survival time when compared with rats administered free IL-2 or saline-containing liposomes. The number of peritoneal exudate cells (PEC) increased markedly after intraperitoneal injection of Lip-IL-2 and consisted mainly of macrophages. The level of tumor necrosis factor alpha (TNF-alpha) and the intensity of free radicals increased in the ascites at 48 hrs after Lip-IL-2 administration, whereas TNF-alpha was not detected and the intensity of free radicals did not increase after free IL-2 administration. Our findings suggested that entrapment of IL-2 into liposomes enhanced its potential for cancer therapy, presumably by activating macrophages to produce TNF-alpha and free radicals. PMID- 1518293 TI - Posthemipelvectomy hernia. AB - We present four patients who developed posthemipelvectomy hernias. Identified etiologic factors include infection at the time of hemipelvectomy, radiation therapy, and excessive weight gain. Two patients were reconstructed using local tissues, and two required prosthetic materials. There were no hernia recurrences, although two patients died of recurrent cancer. PMID- 1518294 TI - The value of nuclear morphometry in the management of patients with colorectal polyps that contain invasive adenocarcinoma. AB - Haggitt's classification is a useful guide in the management of patients with large bowel polyps which contain invasive adenocarcinoma in that patients with levels 1 to 3 require no operation. Nuclear morphometry has been shown to be a useful prognostic discriminant for patients with invasive carcinoma of the large bowel. The nuclear shape factor of 44 polyps with invasive carcinoma was studied to determine whether this parameter was of value to define those patients with Haggitt level 4 who should have a resection. The shape factor of 50 interphase nuclei was obtained through the use of image analysis by tracing the nuclear profiles as digitized on a video screen. The nuclear shape factor was defined as the degree of circularity of the nucleus, a perfect circle recorded as 1.0. Our previous experience showed a nuclear shape factor greater than 0.84 was associated with a poor outcome. The overall mean shape factor was 0.71 (0.59 0.85). There was a tendency for the patients with residual disease to have values in the upper range. Our findings suggest that nuclear morphometry fails to add any predictive information in this clinical situation. PMID- 1518295 TI - Quality of life in bone tumor patients comparing limb salvage and amputation of the lower extremity. AB - In 33 long-term survivors of lower extremity bone cancer quality-of-life data were studied following limb salvage compared to amputation. Self-report questionnaires, semistructured interviews and visual analog scales were used to measure psychoneurotic and somatical distress, activities of daily living, self esteem, and adjustment to illness. Fourteen patients with limb salvage (age 13-56 years, median 24) and 19 patients with an amputation (age 21-53 years, median 27) were evaluated 2-17 years (median 10 years) after surgery. The differences between the two groups were not statistically significant. However, physical complaints were reported more often by limb salvage patients, whereas the amputees showed a trend toward lower self-esteem and isolation in social life, due to their disability. Both groups felt equal diminution of quality of life and disability as measured on the visual analog scale. These findings could support the cosmetic advantage of limb salvage compared to amputation. PMID- 1518296 TI - Late relapse and mortality in stage I large bowel cancer. AB - The outcome was determined for patients with Stage I cancers of the large bowel (colon, rectum, and anus) who were treated from 1982-1989. In 119 consecutive patients, the 5-year survival was approximately 70% (72% by the absolute direct method; 67% by the actuarial life table method). Although the overall 5-year survival was similar to numerous other published reports, it was disturbing to observe that 41% of the living patients had relapsed. Furthermore, although 88/119 (67%) were alive at last report, 2-7 years after treatment, only 23 (19%) were believed to be free of cancer. We conclude that follow-up for more than 5 years and the assessment of disease-free survival are required to evaluate the outcome from Stage I large bowel cancer. PMID- 1518297 TI - A 94 year old male stage IV breast cancer patient showing complete remission under tamoxifen treatment after operation. AB - A 94 year old man with an invasive ductal carcinoma of the breast (T4N2M1, stage IV), underwent a modified radical mastectomy to improve his quality of life. The estrogen receptor status of both the breast tumor and the metastatic axillar lymph nodes was high. Immunohistochemical staining for epidermal growth factor, epidermal growth factor receptor, or c-erbB-2 protein was negative. The patient received only tamoxifen continuously for 3 months, and later apparently showed a complete remission. Therefore, in advanced male breast cancer with a high estrogen receptor status, operation in conjunction with hormone therapy may lead to a favorable result in some cases. PMID- 1518298 TI - Axillary node dissection for early breast cancer: some is good, but all is better. AB - Optimal management of the axillary lymphatics in breast cancer patients remains a contentious subject. Axillary recurrence, while infrequent, may have very significant clinical consequences in the affected patient. Axillary sampling, partial and total axillary lymphadenectomy, radiotherapy, and surgery plus radiotherapy are discussed with attention to efficacy in prevention of axillary recurrence, accuracy of nodal staging, and morbidity. The incidence of axillary recurrence decreases and accuracy of staging increases with the number of lymph nodes resected. There is little difference in incidence of morbidity between partial and total axillary lymphadenectomy. Radiotherapy is not as effective as lymphadenectomy for regional disease control and, when administered following a surgical staging procedure, increases the risk of lymphedema of the ipsilateral upper extremity and, in patients undergoing breast-conserving surgery, the ipsilateral breast. We believe that total axillary lymphadenectomy provides optimal regional disease control and axillary staging with morbidity comparable to that of partial lymphadenectomy. PMID- 1518299 TI - Influence of continuous positive airway pressure on sleep apnea-related desaturation in sleep apnea patients. AB - To investigate the influence of nasal continuous positive airway pressure (CPAP) on apnea-related desaturation, we compared the sleep apnea-related desaturations obtained during a polysomnographic study before and during nasal CPAP in 15 sleep apnea patients. An individual desaturation curve was determined with a regression analysis by plotting the lowest SaO2 value reached during each apnea against its duration; these data were collected throughout the night. At baseline, we only considered the apneas with a preapneic SaO2 value greater than 90% and a minimal SaO2 value above or equal to 60%. For the CPAP study, the preapneic SaO2 value also had to be within 2% the baseline value for the apneas to be retained. Due to the restriction criteria imposed to characterize apnea-related SaO2 falls, residual apneas still had to be recorded with CPAP. These data were analyzed separately for obstructive apnea for non-rapid eye movement (REM) and REM sleep stages. A desaturation curve was obtained from 10 sec to a variable upper limit that corresponded to the longest apnea duration commonly reached during both baseline and CPAP for a given apnea-type and sleep stage. The individual apnea related SaO2 fall was characterized by measuring a desaturation area corresponding to the area under the curve. It was expressed in % SaO2/sec of apnea. CPAP reduced the number of apneas per hour of sleep from 37.5 +/- 6.5 (mean +/- SEM) to 14.3 +/- 3.7 (p = 0.001), and improved the whole night SaO2 level as estimated by a cumulative SaO2 curve. The mean apnea duration was reduced from 22.9 +/- 1.5 sec at baseline to 16.8 +/- 0.5 sec during CPAP therapy (p = 0.005). The preapneic SaO2 value was 94.8 +/- 0.3% at baseline and 95.5 +/- 0.2% during CPAP (p = 0.5). The desaturation area decreased from 267 +/- 48% SaO2/sec at baseline to 152 +/- 41% SaO2/sec during CPAP (p less than 0.001). We conclude that CPAP improves the apnea-related desaturation independently of the shortening of apneas and of any difference in the preapneic SaO2 value. PMID- 1518300 TI - Effect of hydralazine on vascular mechanics in a canine lobar preparation of pulmonary embolism. AB - We studied the effect of hydralazine (H) on pulmonary vascular mechanics in an isolated, in situ, canine lobe model of normal and increased pulmonary vascular resistance (Rp) produced by Gelfoam embolization (GE). Pulmonary pressure-flow (P Q) curves from 24 lobes were obtained at baseline and after each intervention. Hemodynamic parameters for analysis included: the mean critical closing pressure (Ppai), vascular conductance (1/Rp), lobar flow (QL), and the pulmonary inflow pressure (Ppa) at different levels (50, 100, 200, 400, and 600 ml/min) of a fixed flow. After the preparation was stabilized, the 24 lobes were classified into 2 groups. For group 1 (n = 8) we studied the effect of H on the normal pulmonary vasculature. In group 2 (n = 16) we studied the effect of GE. Following GE, this group was further divided in half. For group 2A (n = 8) we followed the natural history of GE with measurements at 15 and 60 min. For group 2B (n = 8) measurements were done 15 min after GE and repeated again 15 min after the infusion of H. For group 1 lobes, H promoted a significant decrease (p less than 0.001) in Ppa at fixed flows of 200, 400, and 600 ml/min compared to baseline, with no change in Ppa for flows below 100 ml/min. QL and 1/Rp increased (p less than 0.01), and there was not any significant change in Ppai. In group 2A lobes, GE produced an increase in Ppa at all levels of flow (p less than 0.01), QL and 1/Rp decreased (p less than 0.05), and there was an increase in Ppai (p less than 0.05). These changes remained stable over the 60 min of observation. For group 2B lobes, GE produced the same hemodynamic changes as in group 2A, and the infusion of H caused a decrease in Ppa at flows between 100 and 300 ml/min. (p less than 0.01) with no change in Ppa at flows below 100 ml/min. QL and 1/Rp increased (p less than 0.01) and Ppai did not change compared to 15 min after GE. We conclude that in the normal canine pulmonary vasculature as well as in the model of GE, H decreased Rp and did not affect mean critical closing pressure, all of which may be explained by an increase in vascular conductance due to an increase in vascular distensibility. PMID- 1518301 TI - Is there a T-cell form of chronic lymphocytic leukemia? PMID- 1518302 TI - Granulocyte-macrophage colony-stimulating factor modulation of the inhibitory effect of transforming growth factor-beta on normal and leukemic human hematopoietic progenitor cells. AB - Experiments were undertaken to investigate the molecular basis of primitive hematopoietic progenitor cell regulation in both the long-term culture system and in methylcellulose, particularly with a view to characterizing factors either able or unable to influence the behaviour of primitive leukemic cells from patients with chronic myeloid leukemia (CML). Long-term cultures of CML cells with or without irradiated normal marrow feeder layers were initiated from peripheral blood cells of CML patients with high white blood cell counts. Three weeks later the effect of exogenously added transforming growth factor-beta 1 (TGF-beta 1) on progenitor cycling status was examined. A single addition of 5 ng/ml TGF-beta 1 was able to reversibly arrest the otherwise uninterrupted turnover of primitive leukemic erythroid and granulopoietic progenitors for a period of up to 7 days both in the presence and absence of a normal adherent cell population. When TGF-beta 1 was incorporated into methylcellulose cultures, its ability to inhibit colony formation by CML progenitors showed the same differential activity on primitive cell types exhibited by normal progenitors. Dose-response curves for analogous populations of normal and leukemic cells were indistinguishable. Increasing the concentration of granulocyte-macrophage colony stimulating factor (GM-CSF) in methylcellulose colony assays decreased the sensitivity displayed by normal clonogenic cells to TGF-beta 1 and no differences were detectable when CML cells were used in such regulator competition experiments. These findings support a general model of primitive hematopoietic cell regulation in which entry into S-phase is determined at the intracellular level by multiple convergent pathways that may deliver either positive or negative signals from activated cell surface receptors for distinct extracellular factors. The present study shows for the first time that primitive CML progenitors exposed to TGF-beta 1 in vitro can be transiently blocked in a noncycling state for several days without loss of viability and that the mechanisms responsible for the emergence and maintenance of a clonal population of CML cells in vivo do not appear to involve changes in their sensitivity to TGF beta 1. It is thus unlikely that the heightened proliferative activity exhibited by primitive CML progenitors both in vivo and in long-term culture can be explained by an abnormality in the intracellular mechanisms normally activated by TGF-beta 1 receptor-ligand binding. We suggest that primitive CML cells are either defective in their ability to see (or activate) endogenously produced TGF beta 1, or are defective in their responsiveness to another, undefined, regulator. PMID- 1518303 TI - Post-remission therapy of acute myelocytic leukemia in adults: curability breeds controversy. AB - The curability of acute myelocytic leukemia (AML) in adults relies upon two treatment strategies. The first is induction therapy to effectively reduce the patient's leukemia burden and allow for recovery of normal hematopoiesis. Once this is achieved and the patient enters a complete remission, further potentially curative post-remission therapy can be administered. Induction therapy has not changed significantly over the past two decades, relying primarily on conventional-dose cytarabine and an anthracycline combination. Post-remission therapy, on the other hand, has changed with the introduction of more intensive and aggressive cytoreductive treatment as well as utilization of myeloablative regimens followed by either allogeneic or autologous bone marrow transplantation (BMT). The scope of this review is to evaluate the different curative post remission treatment approaches for adult patients with AML. Discussions will focus on younger patients (less than 65 years) with responsive disease who enter a complete remission and then have post-remission therapy options available to them. Often, decisions concerning post-remission therapies are based solely on age and the availability of compatible donors; however, since understanding of the biology of leukemia has expanded and treatment strategies have improved, our ability to recommend particular treatment approaches has also evolved. We are now in a position to recommend therapeutic options based on disease and host characteristics. PMID- 1518304 TI - Co-induction of c-fos and junB during the latent period preceding commitment of Friend erythroleukemia cells to differentiation. AB - Chemically induced differentiation of Friend murine erythroleukemia cells (F MELC) is a multistep process with a latent period of about 12 h preceding irreversible commitment to terminal maturation. To gain understanding of the early genetic response of F-MELC to the dimethyl sulfoxide (DMSO) inducer of F MELC differentiation, we have investigated by Northern blot analysis the expression of fos and jun family genes that encode components of the transcription factor AP-1 complex. Our results show that c-jun mRNA is not detected at any time in untreated and DMSO-treated F-MELC. In contrast, DMSO induced differentiation of F-MELC is associated with an early and transient induction of c-fos and junB mRNAs by 2 to 8 h treatment while in presence of dexamethasone, an inhibitor of F-MELC commitment, c-fos mRNA is not detected and junB mRNA remains at basal levels. junD mRNA is detected at low levels in untreated F-MELC and remains unchanged during DMSO treatment. Furthermore, DMSO treatment in a F-MELC cell line resistant to DMSO-differentiation does not result in an early induction of c-fos and junB mRNAs. Taken together, these results indicate that the DMSO-induced F-MELC differentiation is accompanied by an early co-induction of c-fos and junB during the latent period preceding the commitment to erythroid maturation. PMID- 1518305 TI - Factors affecting the in vitro evolution of a myeloma cell line. AB - A continuously growing plasma cell line has been established from the bone marrow of a multiple myeloma patient. Initial growth of the cells was dependent on the presence of bone marrow stromal cells. Following initial outgrowth the cells were maintained by transfer onto non-autocthonous bone marrow stromal cultures. Following approximately one year of continuous growth, a subline was derived which could be grown independently of feeder cells. These stromal-cell independent myeloma cells nevertheless retained dependence for a growth factor present in stromal-cell-conditioned media. The relevant factor in the conditioned media was determined to be interleukin-6 (IL-6). The cells also ultimately became independent of the conditioned media. These latter cells were shown to contain mRNA for IL-6 and eventually began to secrete IL-6. This cell line has thus progressed from complete dependence on stromal cells to IL-6-dependent growth in the absence of stromal cells to complete self sufficient growth. This in vitro progression may reflect an in vivo pattern of myeloma development. PMID- 1518307 TI - Interleukin-2 induction of lymphokine-activated killer activity in the peripheral blood of an acute lymphoblastic leukaemia patient--case study. AB - In this case study an acute lymphoblastic leukaemia (ALL) patient relapsing after autotransplant had remission reinduced with chemotherapy and consolidated after initial response by a course of therapy with recombinant interleukin-2 (rIL-2) given subcutaneously. Immunological parameters measured during therapy demonstrated an increase in the numbers of T cells and in lymphokine-activated killer (LAK) cell activity against autologous leukaemic blasts and LAK-sensitive cell lines. The therapy was well tolerated and administered on an out-patient basis. The patient has remained in haematological remission for over twelve months. Sustained remissions have not been observed previously in relapsed transplant patients using chemotherapy alone. The data suggests that rIL-2 deserves further evaluation in ALL patients who are immunologically intact with residual disease after primary or secondary chemotherapy. PMID- 1518306 TI - Possible correlation between fusion pattern of BCR/ABL mRNA and clinical response to alpha-interferon in chronic myelogenous leukemia. AB - Twenty six patients with Philadelphia chromosome (Ph1) positive chronic myelogenous leukemia (CML) treated with IFN-alpha were classified on the basis of the fusion pattern of BCR/ABL chimeric mRNA determined by a reverse-transcriptase polymerase chain reaction (RT-PCR) method. The relationship between the fusion pattern of BCR/ABL mRNA and the clinical outcome was also analysed. Twelve patients showed M-bcr exon 3/ABL exon 2 (B3/A2) chimeric mRNA and nine had M-bcr exon 2/ABL exon 2 (B2/A2) mRNA. Eleven of the 12 patients with B3/A2 achieved complete hematological response with IFN-alpha therapy, as did three of the nine patients with B2/A2. The mean duration to blastic crisis was significantly longer in the B3/A2 patients (mean 52.4 months) than in the B2/A2 patients (mean 26.2 months) (p less than 0.01). These results suggest that the fusion pattern of BCR/ABL mRNA may affect the therapeutic response to IFN-alpha and clinical outcome in CML patients. PMID- 1518308 TI - Development of T-cell leukaemia in an ataxia telangiectasia patient following clonal selection in t(X;14)-containing lymphocytes. AB - Ataxia telangiectasia is a rare inherited and progressive neurological disorder in which patients show an unusual predisposition to T-cell leukaemia. We report here observations on a patient with a large cytogenetically abnormal clone showing a single t(X;14)(q28;q11) translocation which conferred a proliferative advantage on the cells. The further evolution of this clone to cytogenetically more complex clones of lymphocytes was seen in the patient. She subsequently developed a rapidly progressing T-cell leukaemia, with a CD4+CD8+ T-cell phenotype, about five years after the first appearance of additional chromosome translocations in the clone cells. PMID- 1518309 TI - Postoperative adverse events of common surgical procedures in the Medicare population. AB - Mortality rates are the most widely used measure in assessing patient outcome from hospitalization. However, they may be an insensitive measure of quality for surgical patients because death is a relatively rare outcome. A random sample of patient data (n = 8126) selected from the Medicare files of seven states was used to identify, through chart abstraction, clinical postoperative complications of surgery that could serve as measures of quality. Four surgical procedures were studied: 1) coronary artery bypass grafting; 2) coronary angioplasty; 3) cholecystectomy; and 4) prostatectomy. Severity at admission was controlled for using severity-of-illness models developed with chart-abstracted data to predict adverse events after these four procedures. 30-day mortality rates ranged from 1.0% to 6.6%, while the prevalence of postoperative adverse events identified from chart review was greater (6.9% to 33.3%). There were significant differences between patients with and without adverse events. For example, coronary artery bypass graft patients with adverse events had prolonged postsurgical lengths of stay (18.5 +/- 13.2 vs. 13.2 +/- 6.2, P less than 0.001) and higher mortality rates (15.2% vs. 2.6%, P less than 0.001). The R-square values using clinical indicators at admission to predict the occurrence of any adverse event ranged from 0.05 to 0.13. Clinically meaningful adverse events of surgery can be successfully identified through chart abstraction and appear to be valid measures of postoperative complications among surgical patients. Severity adjustment at admission only modestly predicts the occurrence of these adverse events. PMID- 1518310 TI - Encouraging preventive services for low-income children. The effect of expanding Medicaid. AB - Every year since 1984, Congress has expanded Medicaid to cover an increasing proportion of low-income children. In this study, a multivariate analysis of data from the 1987 National Medical Expenditure Survey was used to determine whether expanded Medicaid eligibility is likely to be effective in encouraging recommended preventive visits for low-income, preschool children. For low-income children who would otherwise be uninsured, a full year of Medicaid increased the probability of any well-child visits by 17 percentage points, and compliance with the guidelines of the American Academy of Pediatrics for well-child visits increased by 13 percentage points. The generosity of Medicaid fees did not alter the magnitude of these effects. However, even if all uninsured children under 200% of the poverty line were eligible for Medicaid, low-income children would continue to lag behind other children in their use of preventive services. Factors other than insurance and income, such as the lower educational attainment of low-income mothers, explain approximately 80% of the gap between children above and below 200% of poverty. The rate of compliance with the American Academy of Pediatrics guidelines was less than 50% for all preschool children. Departures from the recommended schedule of visits were particularly pronounced in the second year of life and may interfere with children receiving the recommended immunizations in a timely manner. PMID- 1518311 TI - Ownership and organizational performance. A comparison of technical efficiency across hospital types. AB - Using a national data base of urban hospitals, the effect of ownership (government, nonprofit, and for-profit) on the technical efficiency of hospitals was examined. Efficiency scores were computed using a method called data envelopment analysis. Controlling for environmental and hospital characteristics, for-profit hospitals were found somewhat less frequently and government hospitals consistently more frequently in the efficient category. When examining highly inefficient hospitals as a percentage of those receiving inefficient scores, for profit hospitals appeared to be highly inefficient relative to the other ownership forms. Government and nonprofit hospitals were somewhat indistinguishable from one another regarding their percentages of highly inefficient scores. For-profit hospitals also tended to use supply and capital asset (hospital size) inputs less efficiently, and service and labor inputs more efficiently than hospitals in the other ownership categories. PMID- 1518312 TI - An analysis of short-term alcoholism treatment cost functions. AB - A number of alcohol treatment studies have documented variations in the average cost of treating alcoholics. However, these studies have provided little explanation for these variations. In this study, three major issues in the measurement of alcoholism treatment costs are investigated: 1) choice of treatment location, i.e., inpatient versus outpatient; 2) interaction of treatment locations in the estimation of costs; 3) impact of type of alcohol problem and comorbidities on treatment costs. The study includes an integrated framework that jointly estimates treatment location and treatment costs conditional on treatment location, concentrating on short-term alcoholism treatment and using insurance claims data to specify a 6-month period beginning with each individual's first treatment for alcoholism. The different treatment types subsumed in the categories alcohol abuse and alcohol dependence are also addressed. Results indicate that comorbidities are crucial in determining treatment location. Once treatment location is determined, however, their effects on treatment costs, while measurable, are statistically insignificant. Partial treatment effects, conditional on treatment location, differ substantially from full treatment effects, which are determined jointly with treatment location. PMID- 1518314 TI - Economies of scope and payment for physician services. AB - Physician payment reform will base payment largely upon physician work. Current reforms assume that services are provided independently, yet physicians may often perform two or more services at one time. There is evidence from other industries that services provided jointly may not require the same total resources as identical services provided independently. This study evaluated whether physician reported work and time were the same for some common services when provided jointly and when provided separately. Six case vignettes were constructed consisting of two services each. Forty-four general internists rated the total work and time required for each vignette performed as a whole, and for the two services performed separately. Total work was estimated using a magnitude estimation technique similar to that used in developing the resource-based relative value scale. For five of the six vignettes, the work rating for performing the services together was significantly less than the sum of the ratings for the separate services. The work savings associated with providing services together ranged from 4% to 30% of the total work of the separate services. A similar reduction was observed for the estimated time to perform services jointly in four of the six vignettes. In no case was work or time lower when services were provided separately. Physicians report lower work and time for at least some pairs of services, compared with providing the same services separately. Reimbursement mechanisms that fail to account for these reductions may provide incentives to combine or add services. PMID- 1518313 TI - An analysis of panel data. The impact of a psychiatric consultation letter on the expenditures and outcomes of care for patients with somatization disorder. AB - In this study, the cost and health outcomes of a psychiatric consultation letter to primary care physicians caring for a sample of patients diagnosed with somatization disorder, a psychiatric condition associated with multiple, unexplained medical complaints, was assessed. To accommodate the small sample size of 73 patients, outcome effects were calculated using panel analysis. Study patients were randomized to a consultation or noconsultation group, and were repeatedly assessed at equal time intervals. Data were analyzed using parsimonious regression models derived from economic theory. During the 1-year follow-up period, a psychiatric consultation letter was associated with a 12% reduction in health care costs ($455 per patient within first year), with no evidence of deterioration in physical, mental, or general health. Less powerful t test comparisons between treated and control groups lead to different conclusions. Reasons for these differences are discussed. PMID- 1518315 TI - The impact of the Texas 1989 motorcycle helmet law on total and head-related fatalities, severe injuries, and overall injuries. AB - The State of Texas implemented a mandatory total motorcycle helmet law for all operators and passengers, effective September 1, 1989. In this study the impact of this intervention on frequency of both total and head-related fatalities, severe injuries, and overall injuries for operators during the subsequent year was quantified. This quantification is important because 26 states in the United States fail to have strict, mandatory helmet laws. The Box-Tiao time-series intervention methodology is used to estimate secular trends before and changes after the implementation of the law, analyzing Department of Public Safety monthly injury accident data for a period of 6 years collected from traffic accident reports filed for each motorcycle injury accident. Trends in fatalities and injuries (except for head-related deaths) estimated before implementation of the law approximated the 9.4% average annual decline in motorcycle registrations. Additional declines of 12.6% and 57.0%, respectively, were estimated for total and head-related fatalities during the year after the law was implemented. Declines of 13.1% and 54.6% were estimated for severe injuries for total and head related accidents. Declines of 12.3% and 52.9% were found for total and head related injuries overall. PMID- 1518316 TI - General practitioners' uncertainty, risk preference, and use of laboratory tests. AB - In this effort to explore the relationships between risk-taking attitude and laboratory test use, three different measures of risk-taking attitudes were obtained in a cross-sectional study of 75 Dutch general practitioners. The measures used were based on a Dutch scale by Grol et al. (dealing with risks and self-reproach in missing serious and in self-limiting diseases), measures from the prospect theory (risk preference in face of gain and in face of loss), and the responses to a direct question regarding the relationship between the use of laboratory tests and the fear of missing diagnoses. Mutual correlation between all the scales was low. The laboratory test use of the general practitioner was measured and divided into two categories: 1 "top ten" tests; and 2) the remaining other tests. Two risk-taking attitude measures explain 28% of the "top ten" test variance and three risk-taking variables account for 38% of the variance in the 'other' test usage. PMID- 1518317 TI - Home blood pressure monitoring. Effect on use of medical services and medical care costs. AB - The objective of this study was to determine whether a hypertension management program in which patients monitor their own blood pressure (BP) at home can reduce costs without compromising BP control. The prospective, randomized, controlled 1-year clinical trial was conducted at four medical centers of the Kaiser Permanente Medical Care Program in the San Francisco Bay Area. Of 467 patients with uncomplicated hypertension who were referred by their physicians, 37 declined to participate in the study; 215 were randomly assigned to a Usual Care (UC) group and 215 to a Home BP group. Twenty-five UC patients and 15 Home BP patients did not return for year-end BP measurements. Patients in the UC group were referred back to their physicians. Patients in the Home BP group were trained to measure their own BP and return the readings by mail. Patients were given a standard procedure to follow in case of unusually high or low BP readings at home. The number and type of outpatient medical services used were obtained from patient medical records for the study year and the prior year. Costs of care for hypertension were calculated by assigning relative value units to each outpatient service. Trained technicians measured each patient's BP at entry into the study and 1 year later. Home BP patients made 1.2 fewer hypertension-related office visits than UC patients during the study year (95% confidence interval (CI): 0.8, 1.7). Mean adjusted cost for physician visits, telephone calls, and laboratory tests associated with hypertension care was $88.76 per patient per year in the Home BP group, 29% less than in the UC group (95% CI: $16.11, $54.74). The annualized cost of implementing the home BP system was approximately $28 per patient during the study year and would currently be approximately $15. After 1 year, BP control in men in the Home BP group was better than in men in the UC group; BP control was equally good in women in both groups. Management of uncomplicated hypertension based on periodic home BP reports can achieve BP control with fewer physician visits, resulting in substantial cost savings. PMID- 1518318 TI - Physician volume and obstetric outcome. AB - Although much has been written regarding regionalization of obstetric services and inferences made about centralization of labor and delivery, little data exist that specifically address the volume-outcome relationship for obstetrics. The purpose of this study was to determine the relationship between physician volume and perinatal outcome as measured by neonatal and perinatal mortality. A sample of 210,547 births to Missouri residents from 1984 to 1987 was studied using multivariate logistic regression with perinatal death and neonatal death as outcomes. No relationship was found between physician volume and outcome. PMID- 1518319 TI - A resource-use model for long-term psychiatric facilities. PMID- 1518320 TI - New challenges in internal medicine. A celebration of the 50th anniversary of the Ochsner Clinic. PMID- 1518321 TI - Academic pursuits in the multispecialty clinic. AB - Although usually viewed as institutions that provide excellence in health care delivery, the larger multispecialty clinics must also be considered as major national academic resources. The professional staffs at multispecialty clinics not only have provided important contributions scientifically but have also made a major clinical impact on overall health care delivery. This issue is dedicated to the founding physicians of Alton Ochsner Medical Foundation and, in particular, to Alton Ochsner who provided the guiding inspiration in a continuing quest to achieve these academic goals. PMID- 1518322 TI - Alton Ochsner. The man and his contributions. AB - Alton Ochsner, the senior founding partner of the Ochsner Clinic and the Alton Ochsner Medical Foundation, is a giant among twentieth century medical figures. He was the first to propose that cigarette smoking is the primary cause of lung cancer, and he and four colleagues founded one of the nation's largest group practices and academic centers. A man of great personal charm, energy, and vision, he wished to be remembered foremost as a teacher. His two-generation polemic concerning the adverse effects of tobacco use provided a rich legacy for the amelioration and prevention of disease. PMID- 1518323 TI - The role of the multispecialty clinic in health care delivery in the twenty-first century. AB - The major multispecialty clinics have established their niche as centers of excellence in coordinated patient care and patient-centered teaching and research. They will be increasingly dependent on local practice and participation in health care plans in future years. Their status as referral centers will hinge on their documentation of cost-effective care of high quality for the ultratertiary patient and on their ability to be recognized for this care by employers, insurers, and national health plans. PMID- 1518324 TI - Graduate education in the multispecialty group. AB - Graduate education traditionally has had different reasons for being in the multispecialty clinic. Practitioners in the multispecialty clinics have learned that the best way to ensure high quality patient care is with a graduate education program. This article reviews the components of graduate education in a multispecialty setting. PMID- 1518325 TI - Development of innovative therapies in the large multispecialty clinic setting. AB - Innovation is intrinsic to medicine and to medical progress. As American medicine enters the twenty-first century, it is confronted with enormous opportunities to innovate both in the science and practice of medicine. Indeed, medicine is challenged to do so by society. Cellular and molecular medicine, along with new insights derived from health care research, offer the opportunity to improve the health of the American people without unduly taxing the economy. Research and innovation in these areas are within the grasp of many clinics, and it would seem important that, because they are major providers of health care, as many clinics as possible aggressively enter these fields in preparation for delivering health care in the next century. PMID- 1518326 TI - The multispecialty clinic in a changing environment. AB - The Ochsner Clinic, faced with a health care delivery environment undergoing dramatic changes, developed a strategy that included the addition of primary care specialists, satellite neighborhood clinics, a distant (regional) multispecialty clinic, and a health maintenance organization. The fundamental changes necessary for a group practice to internalize such a strategy are discussed. The opportunities for graduate medical education and research in the new environment are described. PMID- 1518327 TI - Myocardial revascularization. Coronary angioplasty and bypass surgery indications. AB - Coronary artery bypass grafting (CABG) and percutaneous transluminal coronary angioplasty (PTCA) have been performed increasingly over the last 20 and 10 years, respectively. The growth in PTCA is both complementary and threatening to CABG. The controversy between cardiologists and cardiac surgeons over the role of each procedure will no doubt continue as new devices are developed for coronary interventions. This article reviews the controversy and provides information to internists so that they will be fully prepared to advise patients about their treatment options. PMID- 1518328 TI - Options for percutaneous coronary and peripheral revascularization. AB - Angioplasty has become an established treatment for both coronary and peripheral atherosclerosis, and a number of new techniques and devices promise to improve the results of percutaneous intervention during the coming decades. It is likely that balloon angioplasty will remain the percutaneous treatment of choice for both coronary and peripheral intervention; however, we look with hope toward the development of new devices that will expand the role of percutaneous angioplasty and improve the long-term success of these procedures. As technical expertise grows with the new procedures, prospective randomized trials comparing them with standard PTCA will be required to enable physicians to judge their clinical utility. PMID- 1518329 TI - Infections in orthotopic heart transplant patients at the Ochsner Medical Institutions. AB - Ninety-five orthotopic heart transplants were performed at the Ochsner Foundation Hospital. Twenty-nine of 62 patients followed for 1 year had 48 major infections, including 20 bacterial, 15 viral, 7 fungal, and 6 parasitic. Eighty-six percent of all patients survived 1 year, but infections caused five of the nine deaths. Improved diagnosis and therapy of disseminated aspergillosis could have prevented two deaths. PMID- 1518330 TI - Infections in the compromised host. AB - The normal defense mechanisms against infection include (1) normal skin and mucous membranes, (2) humoral immunity, (3) phagocytic system, and (4) cellular immunity. The compromised (immunocompromised) host is an individual who has one or more deficiencies in these defense mechanisms. This article reviews potential infections in the compromised host as well as an approach to evaluation of these patients. PMID- 1518331 TI - Gallstone disease. Pathophysiology, epidemiology, natural history, and treatment options. AB - In 1991, only symptomatic gallstones should be treated. The treatment of choice for all gallstones continues to be surgical removal. Except for stones in the common bile duct, which are amenable to removal by endoscopic papillotomy, nonsurgical treatment of gallstones should be investigated further before it can have widespread applicability. The major challenge in the future may be medical prevention of gallstone formation in susceptible individuals. Laparoscopic cholecystectomy seems to have moved to the forefront of surgical therapy in patients who are candidates for the procedure. PMID- 1518332 TI - Selection of patients for peripheral revascularization surgery. AB - The recognition of the extent of vascular disease has introduced several medical subspecialties, radiology and vascular surgery, to a multidisciplinary approach to these problems. Of particular importance is the primary care physician, who often is the first to see these patients and should be familiar with common vascular problems. Only then will initial care and disposition be appropriate. PMID- 1518333 TI - Innovative therapies in hematology and oncology. AB - As one can see, there are a number of new and exciting advances in the prevention, detection, and treatment of various malignancies. We anxiously await the future to see the exact integration of the tremendous advances taking place in the cellular and molecular biopsy of disease and its application to the therapy of patients. PMID- 1518334 TI - Selection of patients for kidney organ transplantation. AB - Renal transplantation is a viable alternative for most patients with end-stage renal disease, either before or after the institution of dialysis. Evaluation of potential recipients is necessary before transplantation and is mandatory to exclude patients who are likely to have a poor outcome. Such evaluation also may identify special problems and conditions in patients with end-stage renal disease who will require intervention before transplantation. Identification and evaluation of each transplant donor is also very important. Although organs from related living donors usually have better long-term function, survival, and fewer complications, most efforts in the transplantation community are spent attempting to extend the survival of cadaver kidney transplants. This goal could be accomplished by increasing availability of cadaver organs, improving histocompatibility of donor-recipient pairs, and improving available immunosuppressive therapy. PMID- 1518335 TI - Cardiac transplantation: clinical aspects of recipient selection. AB - The improved outcome following cardiac transplantation has produced changes in the traditional criteria for potential candidates. We have analyzed these changes and the clinical aspects involved in the selection process, which are of critical importance to assure an excellent result of cardiac transplantation in patients with advanced heart failure. PMID- 1518336 TI - Selection of patients for lung transplantation. AB - The number of lung and heart-lung transplantations is growing rapidly, and hundreds of combined heart-lung, single-lung, and double-lung transplantations have been performed to date, resulting in increased survival and improved quality of life for patients with end-stage pulmonary disorders. Improved surgical technique, immunosuppression, and optimal patient selection are largely responsible for this success. Although the indications for transplantation continue to expand, the number of potential recipients far exceeds the number of available donors, making the evaluation and selection process vital to the success of any transplantation program. A multidisciplinary approach is presented that can be expected to eliminate a large number of prospective candidates and thus enhance matching limited donor organs with transplantation candidates. PMID- 1518337 TI - The role of the clinician in the selection of patients for liver transplantation. PMID- 1518338 TI - Patient selection for pancreas transplantation. AB - Pancreas transplantation is the only currently available potential cure for type I diabetes. Because of the complications of the procedure and the toxicity of immunosuppression, patients must be carefully selected. The procedure can be justified in patients who already require immunosuppression for a renal allograft. The benefits of improved quality of life and protection from the development of nephropathy in the kidney allograft are significant. Pancreas transplantation alone is harder to justify; the risks of immunosuppression would seem to outweigh the known benefits of normalization of blood glucose. Before pancreas transplantation gains wide acceptance, the graft survival rates must improve. Currently, pancreas graft survival rates are greater than 80% at 1 year, but less than 50% 5 years after the transplantation. Improvement in these rates may occur with the development of more effective and less toxic immunosuppressive agents. Continued improvement in surgical technique should also contribute to overall pancreas transplantation success. Until then, however, pancreas transplantation should be viewed as a therapy for only selected patients in whom the benefits clearly outweigh the risks. PMID- 1518339 TI - Total joint replacement of the hip and knee. AB - Total hip and knee replacements are among the most common orthopedic surgical procedures performed on patients with arthritis. The procedures are highly successful in appropriately selected patients. The authors approach total joint replacement from a medical perspective, emphasizing indications, contraindications, preoperative evaluation, clinical outcome, and potential complications. PMID- 1518340 TI - Bacteriological and physiological research styles in the early controversy on the nature of the bacteriophage phenomenon. PMID- 1518341 TI - Change and continuity in the cottage hospitals c. 1859-1948: the experience in East Anglia. PMID- 1518342 TI - Anti-malarial policy in the Madras Presidency: an overview of the early decades of the twentieth century. PMID- 1518343 TI - Thomas Jefferson's University of Virginia and the Paris hospitals on the eve of the French Revolution. PMID- 1518344 TI - Sir Patrick Manson: physician to the Colonial Office, 1897-1912. PMID- 1518346 TI - Preliminary results with the Clarion cochlear implant. AB - A new cochlear implant has become available. This device, called the Clarion Multichannel Cochlear Implant, is the result of collaborative efforts between the University of California, San Francisco (UCSF), the Research Triangle Institute (RTI), Research Triangle Park, North Carolina, and the device manufacturer and sponsor, MiniMed Technologies of Sylmar, California. The Clarion represents a new generation of multi-programmable cochlear implant systems. Options in waveform, the stimulation mode, and the temporal distribution of the signal permit the device to be optimally customized for each individual patient. The speech coding scheme offering the greatest opportunity for speech recognition can be selected. The first Clarion recipient has recently been implanted at UCSF, initiating the Clarion's investigational clinical trials. A description of the device and preliminary patient results are presented. PMID- 1518345 TI - Auditory performance of children with cochlear ossification and partial implant insertion. AB - The management of the profoundly deaf child with a cochlear implant poses a special challenge, particularly when total ossification of the cochlea is present. In this setting, insertion of an electrode array into a child's cochlea is often difficult. Our experience supports the feasibility of partial insertion of a multichannel implant into the basal turn of an ossified cochlea. Five children with ossified cochleae who had undergone partial implantation of a multichannel electrode were compared with the performance of matched controls who had full insertion of multichannel implants. No dramatic differences were detected during a 6- to 18-month follow-up period on selected test measures. These preliminary results suggest that active electrode number may exert a limited effect on performance with a cochlear implant. Drilling out the basal turn of an ossified cochlea in conjunction with partial insertion of a multichannel implant appears to be an acceptable surgical and rehabilitational alternative for placement of a cochlear implant prosthesis in children with complete cochlear ossification. PMID- 1518348 TI - Cochleovestibular nerve compression syndrome. II. Vestibular nerve histopathology and theory of pathophysiology. AB - The present study was undertaken to systematically examine and characterize pathological changes in vestibular nerve specimens obtained at surgery in patients with symptomatic cochleovestibular nerve compression syndrome (CNCS). Vestibular nerves were obtained in six cases of CNCS and were intermingled with vestibular nerves obtained in cases of Meniere's disease. All of the nerve specimens were coded and reviewed microscopically in a blind-study fashion by the neuropathologist. The vestibular nerves obtained from CNCS cases showed significant endoneurial fibrosis, compared to controls (specimens from patients with Meniere's disease). Based on observations in this study, as well as the clinical symptoms and audiovestibular test findings in these patients, a theory of pathophysiology in CNCS of the cochleovestibular nerve is proposed. The implications of this theory are discussed with respect to the diagnosis of CNCS. PMID- 1518347 TI - Cochleovestibular nerve compression syndrome. I. Clinical features and audiovestibular findings. AB - Cochleovestibular nerve compression syndrome (CNCS) is the term used to describe a group of audiovestibular symptoms thought to be due to a vessel compressing the cochleovestibular nerve. These symptoms include recurrent vertigo, continuous disequilibrium and acquired motion intolerance. Recently, Moller reported that CNCS can be diagnosed based on abnormalities in the auditory brainstem response (ABR). After specifically excluding all other vestibular disorders, 63 patients with symptoms suggestive of CNCS were identified. These patients were systematically evaluated with a standard neurotologic test battery, and the results were reviewed retrospectively. Hearing loss was found in 51 (81%) of 63 cases, including 33 cases of unilateral high-frequency loss and 14 cases of middle-frequency loss. ABR data were interpreted with respect to Moller's criteria, and abnormal studies were found in 42 (75%) of 56 cases. Abnormal electronystagmograms were found in 57 (93%) of 61 cases. Thirteen of the patients subsequently underwent a posterior fossa procedure for vertigo and, vessels were found in contact with the cochleovestibular nerve in 11 of 13 cases. The results of this study suggest that the majority of CNCS patients have neurotologic test findings that suggest an abnormality of the cochleovestibular nerve. The results and their implications are discussed. PMID- 1518349 TI - Experimental otitis media with effusion induced by middle ear effusion. AB - Experimental otitis media with effusion was induced in chinchillas by middle ear effusion, which was induced by an injection of immune complex into the tympanic cavity. To elucidate the pathogenesis of otitis media with effusion, cytologic and biochemical findings of the effusion and histopathology of the middle ear mucosa of effusion-induced chinchillas were compared with those of experimental otitis media with effusion induced by different procedures; eustachian tube obstruction, intratympanic inoculation of endotoxin, and immune reaction. No significant differences were seen in cytology, biochemistry, and histopathology among OMEs induced by these procedures. However, middle ear effusions, when compared with the corresponding sera, were proven to contain higher amounts of histamine and prostaglandin E2. These findings seem to demonstrate that middle ear effusion containing a large number of inflammatory mediators is essential for induction and prolongation of inflammatory reaction in the middle ear. PMID- 1518350 TI - Hypoplastic endolymphatic sac, hydrops, and Mondini deformity: a case report. AB - The Mondini deformity of the inner ear is usually associated with a large vestibular aqueduct and endolymphatic sac. The authors present a case with a hypoplastic sac and endolymphatic hydrops, which are presumed to be the cause of the Meniere's syndrome symptoms that occurred in mid-life. PMID- 1518351 TI - Presence of urokinase-type plasminogen activator (u-PA) in tissue extracts of antrochoanal polyp. AB - Using a biochemical technique, the authors characterized and identified a plasminogen activator (PA) derived from tissue extracts of antrochoanal polyp (AP) and paranasal mucous membrane (PMM) with chronic sinusitis. The results of fibrin zymography indicated that the tissue extracts of AP revealed two lytic zones and that those of PMM revealed a single lytic zone on fibrin-agarose plates. One of the AP zones exhibited the same relative mobility as the PMM zone (molecular weight: 65 kd), while the other AP zone had a smaller molecular weight (about 54 kd). Goat immunoglobulin G (IgG) fraction of antihuman uterine tissue type plasminogen activator (t-PA) inhibited the 65-kd lytic zones of AP and PMM. Antihuman low-molecular-weight urokinase inhibited only the 54-kd lytic zone of AP, and nonspecific goat IgG failed to inhibit any of the lytic zones. On the other hand, 10(-2) mol trans 4-(aminomethyl)cyclohexane-carboxylic acid (t-AMCHA) inhibited all of the lytic zones. No lytic zones could be observed on plasminogen free fibrin-agarose plates. These findings confirmed that the tissue extracts of PMM contained t-PA, and that those of AP contained both t-PA and urokinase-type plasminogen activator (u-PA). In addition, it appeared that u-PA in inflammatory tissue was related to proliferative changes of the mucous membrane. PMID- 1518352 TI - Nasal airway dilation and obstructed breathing in sleep. AB - Nasal respiratory airflow resistances of awake snorers averaged 0.188 +/- 0.165 Pa/cm3/s (N = 306) and were not elevated beyond the normal range (less than 0.25 Pa/cm3/s). Resistances were decreased substantially from a mean of 0.164 +/- 0.128 to 0.065 +/- 0.037 Pa/cm3/s (N = 72) by a nasal vestibular dilator (Nozovent). Effects of the dilator on breathing disorders in sleep were determined by polysomnographic recordings that included frequency, duration and intensity of snoring, apneas, hypopneas, and oxygen saturation in 10 heavy snorers while asleep with and without the dilator in situ over periods of several hours. No significant changes were detected in these parameters in any stage of sleep. PMID- 1518353 TI - Three-dimensional anatomy of human Scarpa's ganglion. AB - Using a computer-aided three-dimensional reconstruction and measurement method, the authors studied the shape and dimensions of Scarpa's ganglion and interrelations of the ganglion to nearby important anatomical structures in 10 normal human temporal bones obtained from 10 individuals of different ages (12 gestational weeks to 72 years). In the postnatal cases, Scarpa's ganglion was shaped like a distorted hourglass. Although the shape of the ganglion varied somewhat among specimens, a superior division, inferior division, and isthmus ganglionaris were distinguishable in each case. Volume of the ganglion was relatively consistent after birth, so that width and height of the ganglion were inversely correlated with each other (linear regression analysis, P less than .05). There seemed to be, however, a possible postnatal increase in the distances from the ganglion to neighboring structures and in the length of the internal auditory canal; these increases were probably the result of postnatal growth of the temporal bone. Moreover, the width of the ganglion in any single specimen was found to correlate significantly positively with the distances from the ganglion to the vestibular end-organs and the length of the internal auditory canal in that specimen (linear regression analysis, P less than .01). This finding suggests that Scarpa's ganglion may be elongated secondary to the elongation of the vestibular nerve due to the growth of the temporal bone. In fetuses, each portion of the ganglion was less clearly identifiable than that portion in postnatal cases. The dimensions of Scarpa's ganglion were found to have reached maturity around the time of birth. PMID- 1518354 TI - Malignant parotid tumors in 110 consecutive patients: treatment results and prognosis. AB - The UICC 1987 classification system was used to retrospectively analyze the treatment results and prognostic factors in 110 consecutive patients. All of the patients had malignant parotid tumors which had been diagnosed and treated during the period from 1970 to 1986. Treatment consisted of surgery, radiotherapy, or a combination. Malignant mixed tumors were seen in 28% of the patients, mucoepidermoid tumors in 18%, adenoid cystic tumors in 15%, acinic tumors in 13%, undifferentiated tumors in 11%, adenocarcinomas in 10%, and other types in 5%. Ten-year corrected survival rate was 52%, and significant differences of survival were found between: 1. patients with disease stages I through IV (I: 85%; II: 69%; III: 43%; IV: 14%); 2. those with local tumor extension (34%) and without local tumor extension (79%); 3. patients with facial nerve palsy (0%) and without facial nerve palsy (57%); and 4. those with low- or intermediate-grade malignant tumors (69% combined) and those with high-grade malignant tumors (30%). After primary treatment, 45% of the patients were cured, and, additionally, 22% were salvaged after local or neck node recurrences. It is concluded that there is a good correlation between TNM classification of UICC 1987 (stage and local extension of tumor) and prognosis, and that facial nerve palsy and grade of malignancy are important prognostic factors. PMID- 1518355 TI - Single oblique lag screw fixation of mandibular angle fractures. PMID- 1518356 TI - The use of salivary bypass for pharyngeal reconstruction. PMID- 1518357 TI - Refinement of the transpalatine exposure of the nasopharynx. AB - The intrasulcular incision provides excellent transpalatine exposure of the nasopharynx with a viable palatal flap. There is less chance for naso-oral fistula formation since the resulting suture line is always over underlying bone. This safely allows extensive removal of the hard palate. Additionally, the continuous sling suture allows excellent flap reapproximation using the teeth as anchors for the replaced palatal flap. Patients tolerate oral feedings within 24 hours of their operations and require minimal postoperative analgesics. The extended intrasulcular incision offers many advantages over other methods for transpalatine exposures to the nasopharynx. PMID- 1518358 TI - Joseph H. Ogura Memorial Lecture. The academic medical center is a terrible thing to waste. PMID- 1518359 TI - The sensitivity of auditory brainstem response testing in small acoustic neuromas. AB - Auditory brainstem response (ABR) testing is a reliable and sensitive test for retrocochlear pathology in neurotologic diagnosis. Several investigators have reported the sensitivity of ABR testing as 95% or greater. Fifty-one consecutive patients with surgically confirmed acoustic neuromas were examined. Forty patients had sufficient hearing preoperatively for assessment with ABR. In addition, all had been evaluated with gadolinium-enhanced magnetic resonance imaging and conventional electronystagmography. Overall, 34 of 40 patients (85%) had abnormal ABRs. One of 25 patients with extracanalicular tumors had a normal ABR for a false-negative rate of 4%; however, 5 of 15 patients with intracanalicular tumors had normal ABRs for a false-negative rate of 33%. Tumor size and nerve of origin were important factors affecting the ABR sensitivity. The ABR was less sensitive in detecting intracanalicular tumors than in detecting extracanalicular tumors. PMID- 1518360 TI - Nasopharyngeal carcinoma: treatment results with primary radiation therapy. AB - One hundred three patients with nasopharyngeal carcinoma were treated with radiotherapy at UCLA Medical Center from January 1955 to December 1990. Overall survival, disease-free survival, and local control rates were analyzed. In addition, survival from 1955 to 1978 and from 1979 to 1990 were evaluated. Overall 5- and 10-year actuarial survival rates for all patients were 58% and 47%, respectively. Disease-free survival rates at 3 and 5 years were 45% and 30%, respectively. Local, persistent, or recurrent disease in the nasopharynx was the primary cause of failure, occurring in 32% of patients and correlating with the initial tumor size (T stage). Twenty-four percent of patients developed distant metastases, which correlated with nodal status but not with T stage. Seventy-nine percent of patients failed either locally or distally by 4 years. Sex, race, age, and T and N stage categories were evaluated as prognostic variables in terms of survival. Control of primary disease is important in determining long-term outcome. Modern imaging techniques have greatly assisted in the evaluation of disease extent and treatment options. PMID- 1518361 TI - Percutaneous endoscopic gastrostomy in the management of head and neck carcinoma. AB - In patients undergoing resection of head and neck malignancies, structural and functional deficits commonly preclude adequate oral nutrition and prolong hospital stay. To address this issue, the benefit of routine preoperative placement of percutaneous endoscopic gastrostomy (PEG) was studied in a group of these patients. The postoperative course of 89 patients undergoing primary resection of advanced (stage III and IV) squamous cell carcinomas of the upper aerodigestive tract was examined. The hospital stay was reduced by up to 61% with PEG compared to hospital stay with standard nasogastric tube (NGT) alimentation. The difference was statistically significant for primary sites involving the larynx and pharynx, but not for lesions of the oral cavity. For tongue base tumors, there was a trend toward reduced hospitalization which did not reach statistical significance. The fistulization rate was unchanged. The complication rate for PEG was 5%, and morbidity was less with PEG than with NGT. The authors recommend the preoperative placement of PEGs for all patients with advanced carcinomas of the larynx, hypopharynx, and oropharynx. PMID- 1518362 TI - Expression of the major mammalian stress protein in the rat cochlea following transient ischemia. AB - The transient expression of stress proteins in cells exposed to adverse environmental conditions is thought to provide a survival advantage. In the present study, the expression of the major mammalian stress protein, Hsp72, was characterized in the rat peripheral auditory system following varying periods of unilateral cochlear ischemia and reperfusion. Western blot analysis of whole cochlear homogenates revealed Hsp72 expression after as little as 5 minutes of cochlear ischemia. Cochlear Hsp72 immunoreactivity following 10 minutes of ischemia was observed within 2 hours, remained evident through 6 hours, and decreased toward control levels by 12 hours. Preliminary immunocytochemical localization data revealed Hsp72 expression in the outer hair cells. The characterization of Hsp72 expression following transient ischemia represents the first step toward understanding the role that stress proteins have in the protection of the mammalian auditory system. PMID- 1518363 TI - Free-floating endolymph particles: a new operative finding during posterior semicircular canal occlusion. AB - Most clinicians accept cupulolithiasis as the pathophysiological mechanism underlying benign paroxysmal positional vertigo (BPPV.) According to this theory, a cupular deposit induces a gravitational effect on the posterior canal crista. Posterior semicircular canal occlusion is a new operative procedure for treating incapacitating BPPV. It is postulated that canal occlusion abolishes endolymph movement within the canal, effectively fixing the cupula and rendering it unresponsive to both angular and linear acceleration (gravity). During two recent canal occlusions, abundant "free-floating particles" were identified within the posterior canal endolymph. When changing the position of the canal in the earth vertical plane, these free-floating particles would move under the influence of gravity. The hydrodynamic drag of the particles would induce endolymph movement with cupular displacement leading to the typical response. This finding supports an alternate explanation to cupulolithiasis as the pathophysiological mechanism underlying BPPV. PMID- 1518364 TI - Transtympanic endoscopy of the middle ear. AB - Modern optical technology has made available fiberoptic and rigid endoscopes with diameters of 2 mm and less with acceptable resolution. Endoscopes of small caliber were introduced through a strategically placed myringotomy or an existing perforation to perform exploration of the middle ear as an in-the-office procedure. This technique is now routinely used as an adjunct in the diagnostic evaluation of patients with suspected middle ear conditions. Exploratory surgery of the middle ear may be avoided or definitive procedures may be planned better based on endoscopic findings. PMID- 1518365 TI - Anterior cricoid split for subglottic stenosis: experience at the Children's Hospital of New Jersey. AB - Twenty-five children with acquired and congenital subglottic stenosis (SGS) were managed with the anterior cricoid split (ACS) operation at the authors' institution from September 1987 to January 1990. Ages ranged from 2.5 months to 5.5 years. Twenty-one (84%) of the children were extubated after 5 to 14 days of nasotracheal intubation and have remained stable after an average follow-up of 10 months. Atelectasis was a common postoperative problem, encountered in 12 (48%) of the patients. Other complications included a tracheocutaneous fistula, prolapse of soft tissue into the tracheal lumen via the cricoid incision, a subglottic granuloma, and 2 cases of prolonged lower extremity paresis following reversal of vecuronium. The results of this retrospective study indicate that the ACS is a valuable first-line procedure for the management of SGS in a variety of pediatric patients. PMID- 1518366 TI - Role of brain histamine H1- and H2-receptors in neostigmine-induced hyperglycemia in rats. AB - We previously reported that when neostigmine, an inhibitor of acetylcholine esterase, was injected into the third cerebral ventricle, the concentration of hepatic venous plasma glucose was increased via central muscarinic receptors in anesthetized rats. To determine whether brain histamine receptors are involved in cholinergic system transmission with regard to central nervous system (CNS) mediated glucoregulation, we examined the effects of the H1 receptor antagonist pyrilamine and the H2 receptor antagonist ranitidine on neostigmine-induced hyperglycemia in anesthetized rats. The injection of pyrilamine (5 x 10(-9)-5 x 10(-7) mol) into the third cerebral ventricle suppressed hyperglycemia induced by intraventricular injection of neostigmine (1 x 10(-9) mol) in a dose-dependent manner. Injection of ranitidine (5 x 10(-9)-5 x 10(-7) mol) into the third cerebral ventricle did not suppress the hyperglycemia induced by neostigmine, but enhanced it in a dose-dependent manner. These findings suggest that neostigmine induced CNS-mediated hyperglycemia is transmitted by not only brain cholinergic muscarinic receptors but also in part by histamine H1 receptors. PMID- 1518367 TI - Effect of naloxone and beta-casomorphin on the hypothalamic-pituitary-luteinizing hormone axis in vitro. AB - The effect of naloxone and beta-casomorphin on luteinizing hormone (LH) release from pituitary cell aggregates, obtained by three-dimensional culture, with or without mediobasal hypothalamic fragments was studied in vitro. Short-term naloxone perifusion at a concentration of 10(-5)M did not modify either basal or LHRH-stimulated LH release from the pituitary cell aggregates. In contrast, a 12 min naloxone perifusion at the same concentration caused an increase in LH release in the mediobasal hypothalamic-pituitary cell aggregate axis. This increase was rapid (12-16 min after time pulse), marked [up to 10 times (p less than 0.004) the initial base line], short (return to the base line secretion 32 40 min after the beginning of the time pulse) and dose-dependent, with a rise greater than 1000% at a concentration of 10(-4) (p less than 0.006). The same effect was observed when a second pulse was applied 48 min after the first one. LH release induced by naloxone was antagonized 56 +/- 2% (p less than 0.03) by beta-casomorphin (an exogenous opiate) at a concentration of 10(-5) M. beta casomorphin alone did not modify LH basal secretion, but inhibited 25.1 +/- 2.4% (p less than 0.008) LH release enhanced by LHRH. These results indicate that naloxone, an opiate antagonist, markedly increases LH release via a mu-type opioid receptor mechanism at the hypothalamic level only, during short-term exposure. PMID- 1518368 TI - Protein B23 (M.W./pI = 37 kD/5.1) is the only major protein extracted from HeLa nucleoli with 3M urea. AB - HeLa nucleoli were isolated using the NP-40 method and subsequently extracted with 3M urea. The extract was incubated at 60 degrees C for 30 min, and precipitated proteins were removed by centrifugation. The supernatant was analyzed by one- and two-dimensional SDS polyacrylamide gel electrophoresis (PAGE). Protein B23 was the only major protein extracted from HeLa nucleoli by this procedure. Using this procedure, 1 mg of protein B23 was obtained from 2 g of HeLa cells. The purity of the extracted protein B23 was 98%, as measured by one- and two-dimensional gel electrophoresis. PMID- 1518369 TI - Effect of tryptophan administration on circulating melatonin levels in chicks and rats: evidence for stimulation of melatonin synthesis and release in the gastrointestinal tract. AB - The administration of L-tryptophan (Trp, 150-300 mg/kg) to rats and chicks causes a rapid and dose-dependent elevation of circulating melatonin. The elevation of serum melatonin was greater after oral compared to the intraperitoneal route of administration of the same dose of Trp (150 mg/kg). The Trp-induced increase of circulating melatonin was unaffected by prior pinealectomy but was almost abolished by a partial ligature of the portal vein. The Trp-induced increase of melatonin in the portal blood preceded that in the systemic circulation. The gut contains considerable amounts of melatonin and the Trp-induced elevation of melatonin was greater in the duodenum compared to the pineal or the blood. The enterochromaffin cells of the gastrointestinal tract appear to be the major source of the Trp-induced increment of circulating melatonin. The possibility is discussed that the sedating, sleep inducing effects of Trp are mediated by the Trp-induced elevation of circulating melatonin. PMID- 1518370 TI - Central interaction of dexamethasone and RU-38486 on morphine antinociception in mice. AB - The central interference induced by dexamethasone and RU-38486, (a glucocorticoid receptor antagonist) on morphine antinociception were studied by using the tail flick test in mice. Dexamethasone, injected intracerebrally (i.c.v.) 10 minutes before morphine, dose-dependently reduced morphine antinociception, whereas RU 38486 which was injected with the same lag time, potentiated it. When dexamethasone and RU-38486 were administered together i.c.v., 10 minutes before morphine, an overall reduction of morphine antinociception was observed, similar to that observed with dexamethasone pretreatment only. The present results strongly suggest a central site of interaction for dexamethasone and RU-38486 on morphine antinociception; the short latency and the dose-related slope for this interaction may suggest a mechanism at least in part different from the glucocorticoid-induced genomic activation. PMID- 1518371 TI - The physiological consequences of glutathione variations. AB - The major low molecular weight thiol inside cells, the tripeptide glutathione (GSH), is of importance for protection of the cell against oxidative challenge, for thiol homeostasis required to guarantee basic functions, and for defence mechanisms against xenobiotics. Since the pathophysiological significance of a perturbed GSH status in human disease is less clear, this review evaluates the consequences of in vivo variations of GSH. Owing to intracellular GSH concentrations above 2 mM depletion of GSH as such has little metabolic consequences unless an additional stress is superimposed. The kinetic properties of GSH-dependent enzymes imply that loss of up to 90% of intracellular GSH may still be compatible with cellular integrity. Mitochondrial GSH, which accounts for about 10% of total cellular GSH, may define the threshold beyond that toxicity commences. Thus, in cases of severe GSH-depletion a substitution of GSH as a therapeutic measure seems justified. Such a severe depletion of GSH has been described for some diseases such as liver dysfunction, AIDS or pulmonary fibrosis. PMID- 1518372 TI - Effects of inorganic iodide, epidermal growth factor and phorbol ester on hormone synthesis by porcine thyroid follicles cultured in suspension. AB - Porcine thyroid follicles cultured in suspension for 96 h synthesized and secreted thyroid hormones in the presence of thyrotropin (TSH). The secretion of newly synthesized hormones was assessed by determining the contents of thyroxine (T4) and triiodothyronine (T3) in the media and by paperchromatographic analysis of 125I-labelled hormones in the media where the follicles were cultured in the presence and absence of inhibitors of hormone synthesis. The hormone synthesis and secretion was modified by exogenously added NaI (0.1-100 microM). The maximal response was obtained at 1 microM. Thyroid peroxidase (TPO) activity in the cultured follicles with TSH for 96 h was dose-dependently inhibited by NaI. One hundred microM of NaI completely inhibited TSH-induced TPO activity. Moreover, both epidermal growth factor (EGF: 10(-9) and 10(-8) M) and phorbol 12-myristate 13-acetate (PMA: 10(-8) and 10(-7) M) inhibited de novo hormone synthesis. An induction of TPO activity by TSH was also inhibited by either agent. These data provide direct evidences that thyroid hormone synthesis is regulated by NaI as well as TSH at least in part via regulation of TPO activity and also that both EGF and PMA are inhibitory on thyroid hormone formation. PMID- 1518373 TI - A synthetic analogue of vitamin D3, 22-oxa-1,25-dihydroxy-vitamin D3, stimulates the production of prostacyclin by vascular tissues. AB - We investigated the effect of 22-oxa-1,25-dihydroxyvitamin D3, a synthetic analogue of vitamin D3, on the production of prostacyclin by vascular tissues using rat aortic rings and A7r5 cells derived from fetal rat aortic smooth muscle. Prostacyclin synthesis by aortic rings of rats treated with 22-oxa-1,25 dihydroxyvitamin D3 was much higher than that of non-treated controls, but did not cause any significant hypercalcemia. Treatment with 22-oxa-1,25 dihydroxyvitamin D3 significantly increased the production of prostacyclin by A7r5 cells for 48 hours in a dose-dependent manner. In time-course studies, cells incubated with 22-oxa-1,25-dihydroxyvitamin D3 or 1,25-dihydroxyvitamin D3 produced prostacyclin progressively over a period of 48 hours. The shortest period of incubation that produced a significant amount of prostacyclin compared with control cultures was 24 hours. We observed that treatment with 22-oxa-1,25 dihydroxyvitamin D3 induced cyclooxygenase mRNA in A7r5 cells. Our data suggest that 22-oxa-1,25-dihydroxyvitamin D3 may possibly be a protective substance against the development of atherosclerosis by modulating prostaglandin metabolism. PMID- 1518374 TI - Suppressive effect of coenzyme Q10 on phospholipase A2 activation in cardiac cells after prolonged swimming. AB - Phospholipase A2 (PLA2) activity is elevated in cardiac microsomal fractions and phospholipids (PL) are much reduced in both the cardiac mitochondria and microsomal fractions from rats subjected to prolonged swimming. Preadministration of coenzyme Q10 (CoQ10 i.v. 30 mg/kg) significantly suppressed these changes. Two groups of 8-week-old male Wistar rats were trained to swim, receiving 30 min of training for 4 days. On the fifth day they were given an intravenous injection of either 30 mg/kg CoQ10 in saline or 1 ml saline. Thirty minutes later they began to swim for 3 hours carrying a weight representing 3% of body weight. On completion of the swim they were sacrified by instantaneous decapitation, and cardiac mitochondria were isolated. Mitochondria were also prepared from saline injected, unexercised control rats. Phosphatidylethanolamine (PE) and phosphatidylcholine (PC) concentrations were measured with HPLC and PLA2 activity was assayed fluorometrically. The mitochondrial concentrations (means +/- SEM, n = 6) of PE and PC were respectively 126 +/- 22 and 140 +/- 22 nmol/mg protein in the exercise-CoQ10 group against 66 +/- 4 and 50 +/- 10 nmol/mg protein in the exercise-saline group. The specific PLA2 activities (expressed as nmol degraded dipyrene phosphorylethanolamine substrate/hr/mg protein) in the microsomes was 0.20 +/- 0.02 in the exercise-CoQ10 group against 0.30 +/- 0.02 in the exercise saline group. These results suggest CoQ10 has a protective effect against an excessive reduction in mitochondrial membrane phospholipids during prolonged exercise. PMID- 1518375 TI - Suppression of the development of uterine adenomyosis by danazol treatment in mice. AB - Inhibitory effects of danazol, an isoxazol derivative of synthetic steroid 17 alpha-ethinyl-testosterone, on the development of uterine adenomyosis, a pathological disorder of endometrial tissue defined as the presence of endometrial glands and stroma in the myometrium, were investigated in mice of SHN strain. Mice treated with 0.5 microgram danazol for 5 weeks during 4-9 weeks of age and killed at 21 weeks of age showed significantly lower incidence of the spontaneous development of adenomyosis than the age-matched intact control mice. The inhibitory effects of danazol were also evident in mice bearing pituitary isografts which were effective in inducing an early and a high incidence of adenomyosis. Furthermore, the treatment with danazol resulted in the decrease of serum levels of luteinizing hormone (LH) and prolactin (PRL) associated with hypofunction of ovaries and persistent diestrus. These results support the usefulness of danazol for the clinical treatment of gynecological disorders except for hypofunction of ovaries. PMID- 1518376 TI - Impairment by cyclosporin A of reperfusion-induced arrhythmias. AB - This study introduces the immunosuppressor, cyclosporin A, as a cardioprotective drug. This effect was analyzed during development of reperfusion/induced arrhythmias after 5-min period of coronary ligation in hearts of rats under anesthesia. The results indicate that cyclosporin, when given before coronary occlusion, at a dose of 20 mg/kg, effectively protects against the high incidence of arrhythmias and the fall in blood pressure induced by reperfusion. In addition, in inhibits the delivery of lactic dehydrogenase and creatine kinase enzymes to the plasma. We propose that the protective effect could be related with its well documented action to restrain Ca(2+)-induced damage of mitochondrial functions. PMID- 1518377 TI - BMY-14802 protects against ischemia-induced neuronal damage in the gerbil. AB - BMY-14802, a selective sigma ligand currently under investigation as an atypical antipsychotic agent, was tested for potential anti-ischemic activity. BMY-14802 (10, 30 and 50 mg/kg) did not produce any stereotyped behavior, ataxia or seizures. When gerbils were pretreated with 10, 30 or 50 mg/kg of BMY-14802 30 min prior to bilateral occlusion of carotid arteries for 5 min, BMY-14802 significantly protected against ischemia-induced neuronal loss in the hippocampus. Thus, BMY-14802 may also be useful as an anti-ischemic agent that does not produce psychotomimetic effects. PMID- 1518378 TI - Endothelin-3 like immunoreactivity in plasma of patients with cirrhosis of the liver. AB - A highly specific and sensitive radioimmunoassay (RIA) has been established for determination of endothelin-3 like immunoreactivity in human plasma to investigate its possible role in hemodynamic alterations due to liver disease. Crossreactivity with other endothelin isoforms was always below 4 %, the lower detection limit following extraction on Sep-Pak C18 cartridges was 0.5 pg/ml. The concentration of endothelin-3 (mean +/- SEM) was 4.16 +/- 0.56 pg/ml (n = 13) in plasma of patients with cirrhosis of the liver, three fold higher than in age matched controls (1.35 +/- 0.27 pg/ml, n = 12, p less than 0.01). Plasma immunoreactivity was confirmed to be endothelin-3 related by reverse-phase HPLC. These data could suggest a role of plasma endothelin-3 in circulatory changes, as they occur in cirrhosis of the liver. PMID- 1518379 TI - Regulation of prostaglandin secretion from epithelial and stromal cells of the bovine endometrium by interleukin-1 beta, interleukin-2, granulocyte-macrophage colony stimulating factor and tumor necrosis factor-alpha. AB - Bovine endometrium was obtained on day 16 of pregnancy (estrus = 0) and separated into epithelial and stromal cell populations. When confluent, the two cell populations were treated for 24 h with cytokines at 1, 10 and 100 ng/ml. Prostaglandin (PG) E2 was the major prostaglandin produced by both cell types. For control cultures, more PGE2 was secreted into medium by stromal cells than by epithelial cells, whereas secretion of PGF was similar for epithelial and stromal cells. Interleukin-1 beta had no effect on prostaglandin production by stromal cell cultures but increased epithelial production of PGE2 and, to a lesser extent, PGF. Conversely, granulocyte-macrophage colony stimulating factor had no effect on epithelial cells but reduced secretion of PGE2 and PGF from stromal cells. There were no effects of interleukin-2 or tumor necrosis factor-alpha on prostaglandin secretion. Results indicate that certain cytokines can regulate endometrial prostaglandin secretion in a cell type-restricted manner. PMID- 1518380 TI - Transfer of liposomes containing dolichol into isolated hepatocytes. AB - Isolated rat hepatocytes were preincubated with egg lecithin liposomes containing [3H]dolichol and [3H]dolichyl ester, and the intracellular levels and distributions of these lipids were subsequently determined after incubation in a liposome-free medium. [3H]Dolichol was recovered initially mainly in microsomes, and no increase with time in the low level of this compound in the mitochondrial/lysosomal fraction could be observed. A small portion of the labeled dolichol was esterified in the endoplasmic reticulum and transferred to the lysosome-containing fraction. [3H]Dolichyl linoleate was initially localized in microsomes and supernatant, but later accumulated in the mitochondria/lysosomes. Dolichyl linoleate was found in the membrane of microsomes, in the membrane and lumen of lysosomes, and in the soluble cytoplasm. Exogenous dolichol recovered in microsomes was not phosphorylated to any significant extent. Liposomal phosphatidylcholine also showed preferential accumulation in microsomes after incubation with hepatocytes. These results indicate that exogenous or endogenously formed dolichyl esters are transferred from the endoplasmic reticulum to lysosomes, probably through the cytoplasm. It appears that fatty acids play a role in targeting these lipids to their intracellular locations. PMID- 1518381 TI - Effect of ethanol on platelet phospholipase A2. AB - Platelet aggregation is known to be inhibited by ethanol, and this has been suggested to be one of the attenuating effects of ethanol in cardiovascular disease. Recent studies have implicated an inhibition of phospholipase A2 induced arachidonic acid release, since the production of prostanoids that are formed from arachidonic acid and are involved in the aggregation process has been shown to be diminished by ethanol. Phospholipase A2 is found in platelets in both a cytosolic form, from where it may translocate to the plasma membrane to release arachidonic acid, and in a secretory form which is released extracellularly upon activation. In the present study, the effect of ethanol on the secretion of phospholipase A2 and on its activity was determined. It was found that ethanol inhibited phospholipase A2 secretion but not its activity. By contrast, the activity of the cytosolic form of phospholipase A2 was inhibited by ethanol. PMID- 1518382 TI - The dual effect of oxidation on lipid bilayer structure. AB - Sphingomyelin membranes were prepared with different levels of oxidative damage caused by tert-butyl hydroperoxide (TBH). Temperature-induced changes in membrane hydrocarbon chain packing (phase transitions) were monitored using infrared spectroscopy. Lipid phase transition characteristics were evaluated from thermodynamic parameters fitted to the experimental transition curve data. At temperatures below the lipid phase transition Tc, hydrocarbon chains pack in an ordered state whereas above the Tc the hydrocarbon chains pack in a disordered state. Compared to the non-oxidized control, the packing of the hydrocarbon chains of mildly oxidized sphingomyelin (less than 10 nmol TBH/mg lipid) was no different at all temperatures below the Tc, and was more ordered above the Tc. The hydrocarbon chains of strongly oxidized sphingomyelin (greater than 10 nmol TBH/mg lipid) were more disordered at temperatures above and below the Tc compared to the control samples. These results suggest that lipid oxidation has a dual effect on lipid order. A more ordered or disordered state may result depending on the degree of oxidation and the state of lipid order prior to oxidation. These results could be important for explaining the structural changes in oxidized membranes high in sphingomyelin such as those found in the ocular lens and liver plasma membranes. PMID- 1518383 TI - Decreased lecithin:cholesterol acyltransferase activity in the plasma of hypercholesterolemic pigs. AB - Lecithin:cholesterol acyltransferase (LCAT) activity levels were determined, as function of plasma total cholesterol (TC) in 13 normocholesterolemic (TC less than 85 mg/dL) and in 28 hypercholesterolemic (TC greater than 98 mg/dL) pigs. The normocholesterolemic group consisted of pigs that carried apo-B allelic genes other than Lpb5 and or Lpb8. The hypercholesterolemic group consisted of Lpb5/x and Lpb5/8 heterozygous and Lpb5/5 homozygous animals. The data reported in this study show that the LCAT activity in the plasma of hypercholesterolemic (HC) pigs (79 +/- 43 units) was significantly lower (p less than 0.0005) compared to the normocholesterolemic controls (175 +/- 45 units). Furthermore, LCAT activity was positively correlated with TC in the normocholesterolemic group (r = +0.54; p less than 0.05), whereas it was negatively correlated with TC in the hypercholesterolemic group (r = -0.73; p less than 0.001). Additional data obtained from incubation experiments suggest that the lower LCAT activity in hypercholesterolemic pigs may be due, at least in part, to inhibition of LCAT activity by components found in the lipoprotein-deficient fractions of the plasma of hypercholesterolemic pigs. PMID- 1518384 TI - Oxysterols in cultured bovine aortic smooth muscle cells and in the monocyte-like cell line U937. AB - Oxysterols in cultured bovine aortic smooth muscle cells and in the monocyte-like cell line U937 were analyzed by gas-liquid chromatography. The following products were detected: 7 alpha- and 7 beta-hydroxycholesterol, 7-ketocholesterol, cholesterol-alpha-epoxide, cholesterol-beta-epoxide, cholestanetriol, and 20- and 25-hydroxycholesterol. The proportions of oxidized cholesterol varied from 1 to 3% of total cholesterol. The concentrations of oxysterols were lower when the smooth muscle cells were maintained in a vitamin E-enriched medium, and were higher in U937 cells when the cells were activated with phorbol myristate acetate. The cell oxysterol content appears to be regulated by factors that inhibit or enhance free radical generation. The concentrations of oxysterols found in cells may serve as an indicator of the extent of lipid peroxidation. PMID- 1518385 TI - Effects of dietary n-3 fatty acid-enriched chicken eggs on plasma and tissue cholesterol and fatty acid composition of rats. AB - The purpose of this study was to examine the effects of feeding n-3 polyunsaturated fatty acid (PUFA)-enriched chicken eggs on plasma and liver cholesterol levels and fatty acid composition in rats. Eggs were collected from laying hens fed diets containing 10% flax seed (Hn-3), 12% sunflower seed (Hn-6), or wheat and soybean meal control (CON). Yolk powders were prepared and fed at the 15% level to weanling female Sprague-Dawley rats for 28 days. Consumption of n-3 PUFA-enriched yolks significantly reduced both plasma and liver total cholesterol. Liver total lipids and phospholipids of rats fed Hn-3 diet were enriched with linolenic, eicosapentaenoic, and docosahexaenoic acids with a concomitant reduction of arachidonic acid in liver phospholipids. The plasma cholesterol of rats fed yolk powders enriched with n-6 PUFA (mainly linoleic acid) was reduced to the same extent as in those fed the n-3 enriched, but the liver cholesterol was significantly increased, indicating differential effects of dietary n-3 and n-6 PUFA. The results demonstrated that the cholesterolemic and tissue lipid modulating properties of chicken eggs could be modified in a favorable way by altering the fatty acid composition of yolk lipids through manipulation of laying hen diets. PMID- 1518386 TI - Effects of bis homoallylic and homoallylic hydroxyl substitution on the olefinic 13C resonance shifts in fatty acid methyl esters. AB - Substitution of a hydroxyl group at the bis homoallylic position (OH group located three carbons away from the olefinic carbon) in C18 unsaturated fatty acid esters (FAE) induces a 0.73 +/- 0.05 ppm upfield and a 0.73 +/- 0.06 ppm downfield shift on the delta and epsilon olefinic 13C resonances relative to the unsubstituted FAE, respectively. If the hydroxyl group is located on the carboxyl side of the double bond of the bis homoallylic hydroxy fatty acid esters (BHAHFA), the olefinic resonances are uniformly shifted apart by [formula: see text] where delta delta dbu represents the absolute value of the double bond resonance separation in the unsubstituted FAE and 1.46 ppm is the sum of the absolute values of the delta and epsilon shift parameters. With hydroxyl substitution on the terminal methyl side of the double bond, the olefinic shift separation is equal to [formula: see text] In homoallylic (OH group located two carbons away from the olefinic carbon) substituted FAE the gamma and delta induced hydroxyl shifts for the cis double bond resonances are +3.08 and -4.63 ppm, respectively while the trans double bond parameters are +4.06 and -4.18 ppm, respectively. The double bond resonance separation in homoallylic hydroxy fatty acid esters (HAHFA) can be calculated from the formula [formula: see text] for cis and [formula: see text] for the trans case when the OH substitution is on the carboxyl side of the double bond. Conversely, when the OH resides on the terminal methyl side, the double bond shift separations for cis and trans isomers are [formula: see text] and [formula: see text] respectively.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1518387 TI - Chemiluminescence detection of 8a-hydroperoxy-tocopherone in photooxidized alpha tocopherol. AB - Photosensitized oxidation products of alpha-tocopherol were analyzed by reversed phase high-performance liquid chromatography (CL-HPLC) in combination with chemiluminescence detection, to measure hydroperoxide derivatives. An intense peak was observed on the chemiluminescence chromatogram, corresponding to 8a hydroperoxy-alpha-tocopherone (alpha-tocopherol hydroperoxide), the identity of which was confirmed by 1H nuclear magnetic resonance and mass spectrometry. Observed peak intensities correlated with the peroxide value of oxidized alpha tocopherol. As little as 50 pmol of 8a-hydroperoxy-alpha-tocopherone was detectable. The CL-HPLC method, which is specific for the detection of hydroperoxides, should prove useful in studies on tocopherol oxidation in foods and biological systems. PMID- 1518388 TI - An extended method for separating and quantitating molecular species of phospholipids. AB - An improved and extended method for separating and quantitating molecular species of four phospholipid classes is presented. Crude lipid extract is first separated into phospholipid classes on a silica column. Each phospholipid class is then separated into molecular species without derivatization using high-performance liquid chromatography on columns packed with octadecyl silica. Quantitation of individual species is achieved by measuring absorbance at 205 nm. Factors for converting absorbancies to mol fractions have been determined. Quantitation by absorbance at 205 nm agrees well with quantitation by gas chromatography which is preferred to quantitation by phosphate analysis. One hundred phospholipid species have been identified. A table of relative retention times of molecular species is provided. Examples of quantitative analyses of species composition are presented. PMID- 1518390 TI - Inhibition of myocardial lipoprotein lipase by U-57,908 (RHC 80267). AB - U-57,908 (RHC 80267) was shown to inhibit lipoprotein lipase (LPL) activity in cardiac myocytes from rat hearts; the concentrations required for inhibition to 50% of control activity were 1.1 microM and 2.5 microM for myocyte homogenates and a post-heparin medium preparation, respectively. The inhibition of LPL activity by U-57,908 was not changed when the concentration of the triolein substrate and apolipoprotein CII activator in the assay was reduced. The availability of U-57,908 as a potent and selective LPL inhibitor may provide a useful experimental approach in studies on lipoprotein metabolism. PMID- 1518389 TI - Alpha-helical requirements for free apolipoproteins to generate HDL and to induce cellular lipid efflux. AB - The structural requirement has been studied for apolipoproteins in their free form to interact with cells, to generate high density lipoprotein (HDL), and to cause cellular lipid efflux (J. Biol. Chem. 266, 3080-3086, 1991). It is shown that human apolipoprotein (apo) A-IV and apolipophorin III of Manduca sexta cause cholesterol efflux from cholesterol-loaded mouse peritoneal macrophages and reduce intracellularly accumulated cholesteryl ester as a result of forming HDL like particles with cellular lipids, as do apoA-I, A-II and E. On the other hand, similar to apoC-III, reduced-and-carboxymethylated human apoA-II had no such effect. Thus, apolipoproteins seem to require at least four amphiphilic helical segments per molecule to express this function. PMID- 1518391 TI - Liver lipid profiles of adults taking therapeutic doses of aspirin. AB - The distributions of lipids of hepatic specimens obtained at autopsy from 7 adult patients who had been taking large amounts of aspirin for arthritis were compared to 7 control samples obtained from livers of autopsied adults without prior liver disease. The total neutral lipid levels of control livers were approximately one third lower than those observed for livers of patients on aspirin. In addition, the phospholipid content of control specimens was significantly greater than that of livers from adult patients that had been on a high dose of aspirin for a long time. Examination of individual lipid classes showed that the concentrations of free fatty acids, triacylglycerols, and mono- and diacylglycerols were highest in livers of patients with aspirin exposure, and that all phospholipids were diminished. Phosphatidylcholines and phosphatidylethanolamines showed the greatest decrease. These results suggest that the livers of patients taking large amounts of aspirin may accumulate fatty acids and neutral lipids due to an impairment in the oxidation of fatty acids by hepatocytes. The data obtained also suggest that needle biopsy of the liver with measurement of distribution of hepatic lipids, perhaps together with histopathologic examination, may provide useful diagnostic information. PMID- 1518392 TI - Centrofacial malignant granulomas. Clinicopathologic study of 40 cases and review of the literature. AB - An important problem in the treatment of centrofacial ulcerations is to establish a precise diagnosis, since similar clinical and microscopic findings can result from many different causes (as in the centrofacial malignant granuloma syndrome [CFMG]). A comprehensive surgical biopsy protocol (known as SNFMI/GMCF), involving microbiology, parasitology, immunology and pathology laboratories, allowed us to evaluate and to treat 40 cases of CFMG, who form the basis of this report. In 13 of them, specific diagnoses were found and curative treatments could be given. In the remaining 27, the optical microscopy pattern met the criteria for CFMG without identifiable origin or the presence of so-called lethal midline granulomas; however, a more precise evaluation with the help of immunofluorescence studies led to the recognition of malignant lymphoma (ulcerative lymphoma of the midface [ULM]). Most of these lymphomas belonged to the T cell lineage; the others were of B lymphoid origin, or, more rarely, of histiocytic origin. Patients with ULM received radiotherapy and chemotherapy with a response rate of 70.3%; however, the toxicity was significant, with frequent occurrence of chemotherapy-induced neutropenia followed by severe infectious facial cellulitis. Six patients were enrolled in a preliminary open trial of treatment with recombinant alpha-2b interferon with little success. Three patients were treated with radiation therapy only, and survived. Thus, CFMG is a syndrome with specific causes and treatments, requiring multiple extensive biopsies to make the correct diagnosis. The recognition of ULM as the cause of the previously called "lethal midline granulomas" leads logically to the use of chemotherapy with growth factors in order to ameliorate its bad prognosis. PMID- 1518393 TI - Parathyroid carcinoma: clinical and pathologic features in 43 patients. AB - Parathyroid carcinoma accounts for 0.5 to 5% of all cases of hyperparathyroidism. We reviewed the clinical, surgical, and pathologic features observed in all patients with parathyroid carcinoma evaluated at the Mayo Clinic from 1920 through 1991. Forty-three patients (22 women, 21 men; mean age, 54 yrs, range 29 72) were identified, including 2 with familial hyperparathyroidism. Information on initial presentation was available in 40 patients: 15 (38%) presented with polydipsia or polyuria, 11 (27%) with myalgias or arthralgias, 7 (17%) with weight loss, and 4 (10%) with nephrolithiasis; 3 patients (7%) were asymptomatic at presentation. Of 31 patients in whom the initial neck examination was recorded, 14 (45%) had a palpable neck mass. The mean serum calcium and serum phosphorus levels were 14.6 mg/dl and 2.3 mg/dl, respectively. Parathyroid hormone levels were elevated in 21 of 21 patients (mean elevation, 10.2 times upper limit of normal). Complications included nephrolithiasis in 14 of 25 patients (56%), bone disease in 20 of 22 patients (91%) and both in 8 of 15 patients (53%). All patients underwent primary surgical resection of parathyroid carcinoma. Twenty-six of 43 patients (60%) required a second operation with 18 patients requiring multiple re-explorations. At the second operation, residual tumor was found in the neck (68%), mediastinum (16%), or both (12%). Six patients received radiation therapy to the neck (5 patients) or bones (1 patient) for recurrent or metastatic disease. Of these, 1 patient appeared cured of parathyroid carcinoma by radiation therapy 11 years after documented tumor invasion of his trachea. Repeated excision of tumor recurrences was an effective means of controlling hypercalcemia in these patients.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1518394 TI - Hereditary and acquired C1-inhibitor deficiency: biological and clinical characteristics in 235 patients. AB - Two hundred and twenty-six patients with inherited C1 inhibitor (C1-INH) deficiency, also known as hereditary angioedema (HAE), have been studied. They belonged to 80 unrelated families, and in 11 of them C1-INH was functionally deficient but antigenically normal (type II HAE). Genetic analysis of type 1 families demonstrated restriction fragment length polymorphisms in 11% and abnormal mRNAs in 25%. In type II families, the site of the mutation appeared to determine the rate of catabolism of the dysfunctional C1-INH and its antigenic plasma levels. Clinical symptoms (subcutaneous and mucous swellings) generally first appeared within the second decade of life. The frequency of symptoms was highly variable from patient to patient, but a few patients remained asymptomatic throughout their lives. Prophylactic treatment with attenuated androgens was administered to 59 patients and was totally effective in 57, without significant side effects. Sixty-seven laryngeal and 15 abdominal attacks were treated with C1 INH plasma concentrate, yielding initial regression of symptoms in 30 to 90 minutes. The acquired deficiency of C1-INH, also known as acquired angioedema, was diagnosed in 9 patients. Eight of them had an autoantibody against C1-INH; the only patient without the autoantibody had associated chronic lymphocytic leukemia. Prophylactic treatment with attenuated androgens was effective in this last patient, while those with the autoantibody against C1-INH benefited from prophylaxis with antifibrinolytic agents. Replacement therapy with C1-INH concentrate was necessary only for patients with autoantibodies and required doses 3 or 4 times higher than those used in HAE. PMID- 1518395 TI - Cardiovascular disease in systemic lupus erythematosus. A study of 75 patients form a defined population. AB - All patients with systemic lupus erythematosus in a prospective, epidemiologically based study within a defined area in southern Sweden were invited to participate in an investigation of cardiac function. From 1981 to 1988, 101 patients were included in the study, and 75 of them were investigated according to a fixed protocol by echocardiography, Doppler cardiography, electrocardiography (ECG) at rest and at exercise, and myocardial scintigraphy (in patients whose ECG became abnormal during exercise). IgG anticardiolipin antibodies (IgG aCL) were determined by ELISA. Twenty of the 75 patients (27%) had valvular disease and 12 of these (60%) had increased concentrations of IgG aCL, compared with 12 of 55 (22%) without valvular disease (p less than 0.01). Pericardial effusion was detected in 14 patients (19%) during the study period. Mild pulmonary hypertension was found in 11 patients (16%), who also had increased frequency of IgG aCL. Myocardial infarction had occurred in 7 patients, 3 of whom were women less than 40 years of age. Echocardiography revealed regional hypokinesis or akinesis in 5 of the patients with myocardial infarction. Exercise testing revealed low work capacity in 13 of 54 patients (24%), the limiting symptoms being mainly exhaustion or musculoskeletal pain. An abnormal resting ECG was found in 9 of the patients participating in the exercise test. During exercise, abnormal ST-depression was observed in 8 patients, 2 of whom developed angina. Myocardial scintigraphy was performed in 6 of these patients, revealing reversible uptake defects in all. Prolonged glucocorticoid treatment was associated with valvular abnormalities as well as myocardial infarction. Valvular abnormalities and IgG aCL appeared to be risk factors for cerebral infarction. PMID- 1518396 TI - George T. Harrell (1908- ). Rocky Mountain Spotted Fever. 1949. PMID- 1518397 TI - Rocky Mountain spotted fever: a present-day perspective. PMID- 1518398 TI - A look at the world. PMID- 1518399 TI - Reducing the risks in pregnant teens who are very young and those with mild mental retardation. AB - A 3-year evaluation of The Children and Adolescent Pregnancy Project suggests that adolescents with mental retardation may be at increased risk for early pregnancy and dropping out of school. The Pregnancy Project is a school-based intervention that primarily serves black and Hispanic pregnant teens with mild to moderate mental retardation and elementary school-age pregnant teens in the same program. Outcome data were presented in terms of four common indicators of teen pregnancy programs: low birth weight, infant mortality, school drop out, and repeat pregnancy rates. Results indicate that serving pregnant adolescents with mild to moderate mental retardation (ages 11 to 19) in the same program with very young pregnant teens (ages 11 to 15) is an effective and developmentally appropriate means of reducing risks. PMID- 1518400 TI - Quality assurance and impact measurement of university affiliated programs. AB - Provisions in the Developmental Disabilities Bill of Rights and Assistance Act (PL 101-496) emphasize the need to measure the impact of federally supported services in promoting the independence and productivity of clients and their integration in community settings. As a part of this overall emphasis, the Administration on Developmental Disabilities (ADD) has initiated a Quality Enhancement System for use in the University Affiliated Programs (UAPs) encompassing both process (formative) and outcome or impact (summative) evaluation. Whereas formative measures and techniques have been used for many years and are well developed, measures and techniques to determine impact have received much less attention in the professional literature. Characteristics of successful UAPs were outlined as a basis for suggesting appropriate measures of impact of UAP programs on clients and their families, on host and affiliated universities, and on the service system. Some barriers to implementation of impact measures in UAPs were discussed. PMID- 1518401 TI - Income allowance policies of state Medicaid agencies as work incentives or disincentives for ICF/MR residents. AB - Results of a survey of six Midwestern states demonstrated that although some state Medicaid agencies have had work incentive policies for ICF/MR residents for some time, others continue to utilize policies that are a disincentive to work. Policy changes toward employment incentives in state Medicaid agencies should improve work opportunities for workers with mental retardation at little expense to the government. PMID- 1518402 TI - Identification of developmental disabilities and health problems among individuals under child protective services. AB - Although a relation between child abuse and developmental disabilities has been established, information about the health and developmental status of children referred to child protective services is not adequately obtained. Case records of 150 children identified to child protective services were reviewed in order to determine the availability of health and developmental information. A screening protocol was developed for the purpose of reviewing case records that has potential for use by child protective services workers. PMID- 1518403 TI - Specialized treatment for behavior problems of institutionalized persons with mental retardation. AB - The extent of use and effectiveness of special treatment options (in-house behavior shaping units, specialized outside referral agencies, and mobile intensive treatment teams) in dealing with behavior problems of persons with mental retardation was determined. A survey was completed by 144 institutions throughout the United States; 86% of all facilities recognized a need for special treatment options to deal with clients who had severe behavior problems. Sixty eight percent of the institutions had presently or in the recent past used at least one of the three treatment options. Comparisons of these options in terms of perceived effectiveness, length of intervention, and type of problem addressed were reported. PMID- 1518404 TI - Social support of mothers of children with mental retardation. AB - Utilization of social support and perceptions of family stress of 80 mothers with a child who had mental retardation were examined. Measures of family stress and social support were administered to subjects with a child in one of three normative transition periods. There were no significant differences in family stress scores across the groups. Analysis of variance procedures revealed significant differences in the utilization of intimate support across the age groups. Implications for further research in this area were discussed. PMID- 1518405 TI - Pinworm eradication in community residential settings for people with developmental disabilities. AB - Pinworm, a common parasitic infestation, can be a chronic nuisance in community and institutional residences for people with developmental disabilities. Asymptomatic human carriage of the parasite and its eggs often prevents eradication from a communal residential setting. The elimination of pinworm from a system of community residential settings through a public health approach was described. PMID- 1518406 TI - Organ-specific distribution of genotoxic effects in mice exposed to cooked food mutagens. AB - The induction of organ-specific genotoxic effects of five cooked food mutagens in Swiss albino mice was investigated in microbial animal-mediated assays. The indicator of the induction of DNA damage was a pair of Escherichia coli K12 strains, differing vastly in repair capacity (uvrB/recA versus uvr+/rec+). All compounds gave positive results in the tested dose range between 2.5 and 40 mg/kg body weight (i.p. administration, exposure time 120 min). 2-amino-3,4 dimethylimidazo[4,5-f]quinoline (MeIQ) and 2-amino-3-methylimidazo[4,5 f]quinoline (IQ) were slightly more genotoxic than 2-amino-3,8 dimethylimidazo[4,5-f]quinoline (MeIQx), 3-amino-1-methyl-5H-pyrido[4,3-b]indole (Trp-P-2) and 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) which caused similar effects. When the compounds were administered orally, higher doses were required to induce repairable DNA damage. The pattern of organ-specific effects was essentially similar for all compounds; genotoxicity was most pronounced in livers and lungs, whereas in kidneys, spleen and testes comparatively lower effects were measured. The activity of PhIP, MeIQ and IQ in the blood was similar to that observed in the liver. The results obtained in vivo were compared with data gained in vitro with subcellular organ fractions. Our findings indicate the following. (i) The concentrations required to induce repairable DNA damage in microbial animal-mediated assays are substantially higher than might be expected on the basis of the liquid suspension tests. (ii) The ranking order of the genotoxicity of the various compounds in vitro is similar to that measured in vivo, but the differences in genotoxic potencies are less pronounced in the living animal.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1518407 TI - Genotoxic effectivity--comparison of 36 nitrated furan and arenofuran derivatives on a quantitative scale. Statistical comparison of T7 and other short-term tests. AB - Thirty-six nitrated furan and arenofuran derivatives were measured and quantitatively characterized by the T7 inactivation test. A wide range of substances previously studied allowed us to compare the collected quantitative data with those obtained by other workers using different short-term tests. Based on comparative statistical evaluation of these data a borderline was determined for the genotoxic effect: compounds having in our short-term test mutagenicity index (MI) values smaller than 8.0 are positive while the higher values represent negative genotoxicity. Classification of 36 nitrofuran/nitroarenofuran derivatives is given both on the basis of the quantitative genotoxicity scale and in terms of +/- on the qualitative scale. All but one compound were found to be genotoxic and the genotoxic activities of these compounds were compared with the results of other carcinogenicity or mutagenicity tests. PMID- 1518408 TI - Flow cytometric micronucleus test with mouse peripheral erythrocytes. AB - Flow cytometric (FC) analysis was applied to micronucleus test with mouse peripheral blood erythrocytes. The method is based on the measurement of peak fluorescence (PFL) of sphered glutaraldehyde-fixed erythrocytes before and after staining with 4',6-diamidino-2-phenylindole (DAPI), in an EPICS V flow cytometer. The frequency of micronucleated erythrocytes (MNEs) is calculated by a computer program comparing PFL data obtained with and without DAPI. To evaluate the method, male ddY mice were treated with 6-mercaptopurine and benzene and blood was collected from tail vein at intervals of 4-7 days. Both microscopic and FC analysis showed a steady increase in the incidence of MNEs, reaching a plateau when about a month had passed from the start of the treatments. The effects of benzo[a]pyrene, mitomycin C,N-ethyl-N-nitrosourea, bromodichloromethane and potassium chromate (VI) were also studied with both the manual and FC assay in samples collected a week after five weekly treatments. The percentages of MNEs obtained manually and by the FC measurements showed good correlation, the former three chemicals being positive and the latter two negative or, in the FC analysis, difficult to classify. Because of the high number of cells examined (50,000/animal), the FC analysis was probably more sensitive than the manual method where only 2000 cells were scored per animal. This was further suggested by (i) steady time responses, also for individual animals, in the FC results on 6 mercaptopurine and benzene, (ii) overall reduced inter-individual variation in the FC measurements, and (iii) detection of MNE induction by mitomycin C at a lower dose level with the FC than the manual analysis.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1518409 TI - A Chinese hamster ovary cell mutant (EM-C11) with sensitivity to simple alkylating agents and a very high level of sister chromatid exchanges. AB - We have isolated a Chinese hamster ovary cell mutant hypersensitive to monofunctional alkylating agents. The mutant, designed as EM-C11, showed hypersensitivity to ethyl methanesulfonate (EMS), methyl methanesulfonate and ethylnitrosourea (8-, 7- and 2-fold, respectively, based on D10 values). About 2 fold increased sensitivity towards 4-nitroquinoline-1-oxide and only slightly increased sensitivity to X-rays (1.4-fold) and mitomycin C treatment (1.6-fold) were found in this mutant. EM-C11 was not hypersensitive to UV irradiation nor to adriamycin. The EM-C11 cells showed approximately 10-fold higher level of spontaneous sister chromatid exchange. The level of spontaneous chromosomal aberrations was 2- to 3-fold higher, but the frequency of EMS-induced chromosomal aberrations was approximately 10-fold higher in the mutant cells, in agreement with the increased sensitivity to killing. As measured by alkaline elution, EM C11 cells showed a defect in the rejoining of single-strand DNA breaks after exposure to X-rays and even more so after the EMS treatment. Genetic analysis revealed that the EM-C11 mutant belongs to the same complementation group as the EM9 mutant described earlier. The XRCC1 gene which complements the defect in EM9 also complements the defect in EM-C11, confirming that these two independently isolated mutants are defective in the same gene. PMID- 1518410 TI - Absence of translocation induction in mouse stem cell spermatogonia by chemical mutagens probably due to selective elimination. AB - In order to discriminate between different mechanisms put forward to explain the low observed yields of reciprocal translocation configurations at diakinesis metaphase I spermatocytes following treatment of mouse stem cell spermatogonia with chemical clastogens, the physiological states of stem cells at the moment of treatment were modified. The cell cycle was shortened by pretreatment with 2 Gy of X-rays and/or the DNA repair capacity inhibited by pretreatment with 3 aminobenzamide. Using these conditions the induction of translocations by ethyl methanesulfonate, N-ethyl-N-nitrosourea, methyl methanesulfonate and Adriamycin was studied. The results indicate that selective elimination of aberration carrying cells is probably to a large extent responsible for the low induction rate of translocations in stem cells by chemical clastogens. The high ratio of simple chromosome breaks versus chromosome exchange type aberrations induced by chemical mutagens might be the main cause of the selective elimination. PMID- 1518411 TI - Interaction of omeprazole with DNA in rat tissues. AB - There has been concern recently over the possible genotoxicity of omeprazole, a potent inhibitor of gastric acid secretion in humans. In order to investigate its possible DNA binding activity in vivo, 14C-labelled omeprazole was administered to male PVG rats, 8-10 weeks old, orally by gavage at a dose of 30 mg/kg. At various times after treatment, animals were killed and DNA isolated from the fundic and antral regions of the glandular stomach, and from the duodenum, ileum and colon. Scintillation counting of the DNA samples revealed a reproducible association of 14C that was not extractable with organic solvents and could not be removed from the DNA by column cartridge chromatography. DNA samples were digested enzymically to deoxyribonucleosides and analysed by reversed-phase high performance liquid chromatography (HPLC). With DNA from each tissue, most of the radioactivity eluted in a peak that was chromatographically distinct from normal nucleosides and from omeprazole itself. Chromatography following partial digestion of DNA gave rise to the same radioactivity elution profiles, whilst chromatography on hydroxyapatite resulted in retention of most of the radioactivity on the column using conditions under which DNA was eluted. These findings suggest either the formation in rat tissues of chemically-labile covalent omeprazole-DNA adducts or, more likely, a strong non-covalent interaction. The apparent DNA binding occurs rapidly in vivo and is short-lived, the maximum levels of radioactive incorporation (equivalent of up to 36 pmol omeprazole/mg DNA) occurring at 0.5 h in fundus, 0.5-1 h in antrum, 1 h in duodenum, 2 h in ileum and at 4-8 h in colon. PMID- 1518412 TI - Effects of adenine arabinoside and coformycin on the kinetics of G2 chromatid aberrations in X-irradiated human lymphocytes. AB - The kinetics of chromatid aberrations have been studied in human lymphocytes exposed to X-rays in the G2 phase of the cell cycle and incubated with or without the nucleoside analogue 9-beta-D-arabinofuranosyladenine (ara A), known to inhibit the repair of DNA double-strand breaks. In the absence of ara A an exponential decrease in frequencies of chromatid breaks occurred which we interpret as repair. Few breaks were observed if samples were harvested immediately following irradiation. The frequency of chromatid breaks at 1 h after X-irradiation (442 per 100 cells/Gy) was similar to that previously observed in Chinese hamster ovary (CHO) K1 cells. However, the exponential decrease of chromatid breaks between X-irradiation and sampling occurred with a t1/2 of 0.87 h, a faster rate than we have previously observed in CHO K1 cells and was not inhibited by 200 microM ara A alone, in contrast with our previous findings in a human fibroblast line. However, in the presence of the ADA inhibitor coformycin, inhibition of break repair was already observed at an ara A concentration of 100 microM indicating that the apparent unresponsiveness to ara A of lymphocyte chromatid break rejoining results from the deamination of this nucleoside analogue. This deamination effect was confirmed by measurements of DNA synthesis which showed stable inhibition of synthesis by ara A only when coformycin was present. Frequencies of chromatid exchanges in irradiated cells remained constant except at the sampling time directly after irradiation, consistent with the view that chromosomal radiosensitivity remained constant throughout the G2 phase, except for the period immediately prior to mitosis.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1518413 TI - The restriction endonuclease AluI induces sister chromatid exchange in Chinese hamster ovary cells. AB - Chinese hamster ovary (CHO) cells were exposed to the restriction endonuclease AluI in the presence of 1.1 M glycerol. Chromosomal aberrations and sister chromatid exchange (SCE) were scored in first post-treatment metaphases following recovery times of 6-18 h. At all recovery times chromosomal aberrations were induced by the enzyme. In AluI-treated damaged cells significant elevations of SCE frequencies were found after recovery times of 12-18 h. These results indicate that SCE, unlike chromosomal aberrations, are induced only in late G1 and early S phase of the cell cycle. The lesions producing SCE are postulated as DNA single-strand breaks and gaps induced by AluI in canonical structures of DNA and in DNA-RNA hybrids. PMID- 1518414 TI - Metabolic alterations produced by cigarette smoke in rat lung and liver, and their modulation by oral N-acetylcysteine. AB - Male Sprague-Dawley rats were exposed whole-body to the mainstream smoke produced by a commercial filter cigarette for 8 consecutive days, accounting for a cumulative exposure to the smoke of 75 cigarettes. Liver and lung S12 fractions were used in the Salmonella mutagenicity test in order to assess either the decrease of potency of a direct-acting mutagen (sodium dichromate) or the metabolic activation of promutagens, including cigarette smoke itself and its condensate, benzo[a]pyrene and its 7,8-diol, the aromatic amine 2-aminofluorene, and the heterocyclic amine 3-amino-1-methyl-5H-pyrido(4,3)indole. Moreover, individual biochemical parameters were measured in the liver and lung of the same rats and, in the case of cytochrome P-450-dependent monooxygenases, also in the heart of untreated or Aroclor-treated rats. The monitored biochemical parameters included aryl hydrocarbon (benzo[a]pyrene) hydroxylase and ethoxyresorufin deethylase in microsomal fractions, epoxide (benzo[a]pyrene-4,5-oxide) hydrolase in both microsomal and cytosolic fractions, glutathione (GSH) and GSH S transferase in the cytosol. Exposure to cigarette smoke resulted in a number of significant metabolic changes, as compared to sham-exposed rats. The most pronounced alterations consisted in a 2.6-fold induction of aryl hydrocarbon hydroxylase in the lung and 8-fold induction of ethoxyresorufin deethylase in the liver, and in a marked stimulation of the liver metabolic activation of all promutagens. The last effect was inhibited by the oral administration of the chemopreventive agent N-acetylcysteine. On the whole, there was a poor correlation between the monitored biochemical and mutagenicity endpoints.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1518415 TI - Benomyl-induced aneuploidy in mouse oocytes. AB - Benomyl (methyl-1-[butylcarbamoyl]-2-benzimidazole carbamate) is a plant fungicide which acts by inhibiting tubulin polymerization. It is also a carcinogen and a teratogen. A substantial number of reports consistently show that benomyl inhibits cellular division and induces numerical chromosome changes in somatic cells, while results from standard genotoxicity assays which measure mutations and structural chromosome aberrations are conflicting. To define further the genotoxic effects of benomyl and to demonstrate the utility of the in vivo mouse oocyte assay for detecting chemicals which induce numerical chromosome changes, we investigated the ability of benomyl to induce numerical and structural chromosome aberrations in mouse oocytes. Superovulated female ICR mice were administered benomyl by oral gavage and oocytes were collected 17 h later. The proportions (and percentages) of hyperploid oocytes were 1/309(0.3), 6/155(3.9), 38/229(16.6), 46/130(35.4), 60/215 (27.9), 42/143(29.4) for control, 500, 1000, 1500, 1750 and 2000 mg/kg respectively. No increase in structural aberrations was observed. These results demonstrate that benomyl specifically induces numerical chromosome changes in mouse oocytes. PMID- 1518416 TI - Ricin and lentil lectin-affinity chromatography reveals oligosaccharide heterogeneity of thyrotropin secreted by 12 human pituitary tumors. AB - Some patients with thyrotropin (TSH)-producing pituitary tumors are more hyperthyroid than others despite similar TSH levels in serum, suggesting that qualitatively different TSH molecules with differing bioactivities may be secreted by different tumors. We used ricin and lentil lectin-affinity chromatography to test whether the TSH oligosaccharides varied among 12 patients with TSH-producing tumors. We found that each tumor secreted heterogeneous isoforms of TSH that differed in their extents of exposed galactose (Gal) residues, and their degrees of sialylation and core fucosylation. These biochemical parameters also varied markedly for TSH secreted by different tumors. Isoforms appeared to reflect poor sialyltransferase activity in two tumors and efficient sialyltransferase in the remainder. TSH secreted by tumors was more fucosylated than TSH secreted by control euthyroid persons. There was an inverse relationship between the sialylation and fucosylation of tumor TSH. No simple relationship between TSH oligosaccharide structures and bioactivity was evident, although mixtures of isoforms having the least and most sialylated TSH seemed to be the most bioactive clinically. In three patients from whom serum and medium TSH were both available, TSH in serum was more sialylated than TSH secreted by the tumor in vitro, perhaps reflecting slow clearance of sialylated isoforms from the circulation. Core fucosylation of serum TSH was less than that of medium TSH. These data prove that human tumors secrete TSH with heterogeneous oligosaccharide structures. PMID- 1518417 TI - The pathobiochemistry of uremia and hyperargininemia further demonstrates a metabolic relationship between urea and guanidinosuccinic acid. AB - To better understand the biosynthesis of guanidinosuccinic acid, we determined urea, arginine, and guanidinosuccinic acid levels in nondialyzed uremic and hyperargininemic patients. These substances were also determined during several years of therapy in one hyperarginiemic patient. Interrelationships of guanidinosuccinic acid levels with their corresponding urea and arginine levels were assessed by linear correlation studies. In uremic patients, a significant positive linear correlation (r = .821, p less than .001) was found between serum urea and guanidinosuccinic acid levels A significant positive linear correlation was also found between serum urea levels and urinary guanidinosuccinic acid levels (r = .828, P less than .001), but not between serum arginine levels and urinary guanidinosuccinic acid levels in hyperargininemic patients. In the intrahyperargininemic patient study, a similar significant positive correlation was found between serum urea levels and the corresponding urinary guanidinosuccinic acid levels (r = .866, P less than .001); the correlation between serum arginine levels and the corresponding urinary guanidinosuccinic acid levels was smaller. The presented analytical findings in uremic and hyperargininemic patients clearly demonstrate a metabolic relationship between urea and guanidinosuccinic acid. PMID- 1518418 TI - No significant effect of vitamin E deficiency or supplementation on collagen linked fluorescence in skin of diabetic rats. AB - It is speculated that oxidative stress in vivo may have some influence on advanced, nonenzymatic, glycosylation end products. However, this has not been demonstrated yet. We assessed changes in collagen-linked fluorescence in the skin of nondiabetic and streptozotocin-induced diabetic rats fed three different diets for 4 weeks that could modify oxidative stress: vitamin E-deficient (D), vitamin E-supplemented (S), and control (C). The serum lipid peroxide level expressed as thiobarbituric acid (TBA) activity in diabetic rats on the S diet (9.6 +/- 1.0 [SE] nmol/L/mL) was significantly (P less than .01) lower than that in rats on the D diet (111.4 +/- 22.4), and similar to that in nondiabetic rats on the C diet (12.4 +/- 2.2). The collagen-linked fluorescence level was significantly (P less than .01) higher in diabetic rats than in nondiabetic rats, which corresponded to the serum glucose and glycosylated hemoglobin levels. However, there were no significant differences in the fluorescence levels among three groups classified by three different diets in both nondiabetic and diabetic rats (21.7 +/- 1.7 arbitrary U/mg collagen for D, 22.3 +/- 2.0 for C, and 22.8 +/- 2.5 for S in nondiabetic rats v 41.2 +/- 4.1 for D, 40.1 +/- 4.7 for C, and 39.3 +/- 3.5 for S in diabetic rats), despite significant changes in serum lipid peroxide levels. Consequently, there were no significant changes found in collagen-linked fluorescence levels in diabetic rats wherein oxidative stress was modified by vitamin E deficiency and supplementation.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1518419 TI - Increased protein turnover in obese women. AB - Some previous studies have indicated that rates of proteolysis and protein synthesis are greater in obese than in lean subjects, whereas others have not supported this finding. In the present study, we have measured postabsorptive protein turnover in a large group (n = 24) of obese women to establish more conclusively whether obese women have higher rates of protein turnover than lean women (n = 12), and to determine whether obese subjects with the greatest abdominal fat accumulation or those with the most severe insulin resistance (as determined by oral glucose tolerance testing) have the highest rates of protein turnover. Leucine appearance rate (Ra) was used as an index of whole-body proteolysis, and the fraction of Ra not oxidized was used as an index of whole body protein synthesis. Leu Ra, oxidation, and incorporation into protein after an overnight fast were approximately 25% greater in obese than in lean women, and were approximately 10% to 15% greater after dividing by lean body mass (LBM) or adjusting for LBM by analysis of covariance. Among obese women, the degree of obesity (over the range of 30% to 47% fat) was not a significant determinant of protein turnover, nor were degree of insulin resistance, visceral fat accumulation (determined by magnetic resonance imaging [MRI]), or subcutaneous abdominal fat accumulation (also determined by MRI). However, the women with the highest rates of protein turnover also had higher waist to hip circumference ratios (WHR). We conclude that even moderate obesity is associated with increased protein turnover, and that this effect is not completely explained by the higher LBM in obese subjects. PMID- 1518420 TI - Benefit from hypocaloric diet in obese men depends on the extent of weight-loss regarding cholesterol, and on a simultaneous change in body fat distribution regarding insulin sensitivity and glucose tolerance. AB - Obesity and an android body fat distribution are related to metabolic disorders. We investigated the interdependences between metabolism, overweight, and body fat distribution in 40 moderately obese men before and after weight-loss. Correlations between metabolic parameters and body mass index (BMI) or waist to hip ratio (WHR) were much weaker in this exclusively obese population than in subjects of all weight categories, but the association between BMI and glucose tolerance (r = -.46, P less than .01) increased significantly after weight-loss. The improvement of metabolic parameters was much stronger in men who achieved normal weight (BMI less than 27 kg/m2) than in those who remained obese (BMI greater than 30 kg/m2, P less than .05). The WHR decreased during the diet (P less than .001), and this decrease and the extent of weight-loss were significantly correlated to an increase in insulin sensitivity (r = -.41, P less than .01) and a decrease in glucose area after an oral glucose load (r = .34, P less than .05). The decrease in apolipoprotein B, total cholesterol, and low density lipoprotein (LDL) cholesterol was significantly correlated only to the extent of weight-loss (r = .34, .31, and .39, respectively; P less than .05). We conclude that it is best to reach normal weight for the normalization of metabolic aberrations. The reduction of cholesterol appears to be dependent on the extent of weight-loss, while the improvement in insulin sensitivity and glucose tolerance apparently is related to both the extent of weight-loss and to a change toward a less android body fat distribution. PMID- 1518421 TI - Competition for transport of amino acids into rat heart: effect of competitors on protein synthesis and degradation. AB - Transport of the neutral amino acids, 2-(methylamino)isobutyrate (MeAIB) and Phe, was examined in isolated rat hearts perfused by the Langendorff method. Hearts were perfused by recirculating for various time periods buffer containing [14C] MeAIB or [14C]-Phe plus desired additions. Uptake of MeAIB was linear for approximately 30 minutes; Phe uptake was linear for a maximum of 5 minutes, and reached a steady state after 15 minutes. Km and Vmax for MeAIB were 1.1 +/- 0.03 mmol/L and 37.7 +/- 0.4 pmol/microL intracellular fluid (ICF)/min; values for Phe were 1.8 +/- 0.02 mmol/L and 364 +/- 5 pmol/microL ICF/minute. Uptake of MeAIB (0.2 mmol/L) was reduced 95% in the presence of Ser (10 mmol/L), and less severely by large neutral amino acids ([LNAA], 10 mmol/L) such as Phe and Leu (by 46% and 54%, respectively). Uptake of Phe (0.2 mmol/L) was reduced by LNAA such as Val, Leu, and Ile (by 51%, 78%, and 81%, respectively), or by commercial preparations used in parenteral nutrition, eg, Travasol or Travasol plus extra branched-chain amino acids (BCAA) (Branchamin); Ser had little effect (8% reduction). Insulin in the perfusion medium increased the fractional rate of protein synthesis. Individual BCAA at physiological concentrations (0.2 mmol/L) did not alter the rate of protein synthesis. Branchamin or Travasol plus Branchamin also had no effect on the rate of protein synthesis in heart, but did depress the rate of degradation. These studies suggest that amino acid transport into heart may be affected by normal levels of plasma amino acids, whereas protein synthesis is not. PMID- 1518422 TI - Pulsatile hormone secretion during severe sepsis: accuracy of different blood sampling regimens. AB - The metabolic response to sepsis is dependent on the hormonal status. However, reported plasma hormone levels vary widely among studies. The persistence of pulsatile secretion, as occurs normally, may explain the observed variability. To study whether pulsatile hormone secretion persists during sepsis and how it affects assessment of the hormonal status from single measurements, we measured growth hormone (GH), prolactin, cortisol, insulin, and C-peptide at 20-minute intervals for 24 hours in eight consecutive patients with severe sepsis. Twenty four-hour averages (mean +/- SD) were 3.3 +/- 2.5 ng/mL for GH, 640 +/- 461 nmol/L for cortisol, 18.2 +/- 4.8 mU/L for insulin, and 3.4 +/- 2.9 U/L for C peptide, at a pulse frequency between 3.3 +/- 2.7 for C-peptide and 10.2 +/- 3.4 for insulin, and an increase of the maximal value in a pulse above the preceding nadir of 131% +/- 13% for cortisol and 376% +/- 386% for GH, as assessed with Cluster analysis. Prolactin levels were below the detection limit in all but one patient, probably due to the administration of dopamine. To determine the accuracy of less frequent blood sampling regimens, we simulated different sampling strategies and compared them with the 24-hour averages. The accuracy of single samples proved inadequate for all hormones. Sampling every 20 minutes for periods of 4, 8, or 12 hours improved accuracy, but intermittent sampling every 1, 2, 4, or 6 hours during a 24-hour period yielded even more accurate results.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1518423 TI - Influence of endurance training on energy intake, norepinephrine kinetics, and metabolic rate in older individuals. AB - The role of physical activity in the regulation of energy intake in older persons is presently unclear. We therefore examined the influence of endurance training on voluntary energy intake and the associated changes in resting metabolic rate (RMR) and norepinephrine (NE) kinetics in seven healthy (six men, one woman) older individuals (69.4 +/- 2.2 years) under supervised living conditions. Energy intake was measured by covert assessment in a clinical research environment during: (1) a 10-day inpatient control period (no exercise); (2) a 10-day light exercise period (150 kcal per session, 3 times/wk); and (3) a 10-day moderate exercise period (300 kcal per session, 3 times/wk). RMR was determined after all three periods, and NE kinetics were assessed before and after training by infusions of tritiated NE ([3H]-NE). No significant change in energy intake was found between the control (2,378 +/- 130 kcal/d) and light exercise (2,449 +/- 104 kcal/d) periods, whereas energy intake increased 17% (P less than .01) during moderate exercise (2,785 +/- 161 kcal/d). Changes in RMR paralleled those of energy intake, as no differences were noted in RMR after control (1.03 +/- 0.12 kcal/min) and light exercise periods (1.04 +/- 0.12 kcal/min), but RMR increased 9% (1.13 +/- 0.14 kcal/min, P less than .01) after moderate endurance training, despite no changes in body composition.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1518424 TI - Malnutrition-related polyunsaturated fatty acid changes in plasma lipid fractions of cirrhotic patients. AB - Cirrhotic patients have both impaired liver function and nutritional derangement. In fact, the prevalence of protein-energy malnutrition (PEM) is very high in these patients. The aim of the present study was to elucidate whether the nutritional status in cirrhosis could be an additional factor that would affect levels of plasma lipids. Plasma lipid phosphorus, cholesterol, and triglycerides (TG), and fatty acid profiles in plasma and plasma fractions were determined in 50 healthy subjects and 92 patients with liver cirrhosis. The cirrhotic patients were prospectively included in three groups according to the result of nutritional assessment: group 1 (n = 38), acceptable nutritional status (including well-nourished and mildly malnourished patients); group 2 (n = 29), moderate PEM; and group 3 (n = 25), severe PEM. The main findings of this study were that the decrease in plasma cholesterol and linoleic, dihomo-gamma linolenic, and arachidonic acid levels of cirrhotic patients was related to the degree of PEM. Cholesteryl esters (CE) appeared to be the most sensitive indicator of lipid changes in cirrhosis. We consider that the role of malnutrition in the changes observed for polyunsaturated fatty acid (PUFA) profiles in plasma lipids of cirrhotic patients may be of major importance, since severe malnourished subjects exhibited the lowest levels of those compounds. Dietary supplementation of both essential fatty acids (EFA) and long-chain PUFA in adequate amounts to the cirrhotic patient might be of importance in the management of the disease. PMID- 1518425 TI - Individual regulation of different hepatocellular functions during sepsis. AB - The purpose of this study was to test the hypothesis that different hepatocellular functions are regulated individually during sepsis. This was done by simultaneously measuring bile production, release of liver transaminases, and synthesis of secreted proteins in perfused livers from control and septic rats. Sepsis was induced by cecal ligation and puncture (CLP); control rats were sham operated. After 16 hours, livers were perfused in situ, and bile flow, synthesis rates of albumin and alpha 1-acid glycoprotein (a major acute-phase protein in rats), and release of glutamic-oxaloacetic transaminase (GOT) and glutamic pyruvic transaminase (GPT) into perfusate were determined. Within the same livers, sepsis resulted in a 54% increase in the synthesis of alpha 1-acid glycoprotein and approximately 30% inhibition of albumin synthesis concomitant with 50% lower bile flow. The concentrations of GOT and GPT in the perfusate increased slightly during the experiments, both when control and septic livers were perfused. The maintained tissue levels of adenosine triphosphate (ATP) and the uptake of Evans blue dye by less than 1% of the hepatocytes, although a late test of viability, suggest that both control and septic livers remained viable during perfusion. The results are consistent with the concept that different hepatocellular functions are individually regulated during sepsis. Thus, impairment of certain hepatocellular functions does not necessarily imply generalized liver failure. PMID- 1518426 TI - Differential metabolic responses to tumor necrosis factor with increase in age. AB - Previous studies have shown varied responses to the effects of tumor necrosis factor (TNF) on glucose and lipid metabolism. To elucidate possible causes for this variation, the present study compared sequential changes in plasma glucose, lactic acid, triglyceride (TG), free fatty acids (FFA), and plasma insulin levels in 1.5- and 16-month-old, normal, fed, male rats, 1 to 6 hours after different doses of intravenous (IV) TNF. In addition, assessment was made of TNF injected intraperitoneally (IP) in precannulated and intact young (1.5 months) rats and of the dose-response (0.25 to 50 micrograms/100 g rat) and the sensitivity to insulin in intact rats. Finally, the metabolic responses and changes in serum insulin and corticosterone concentration after IP TNF were compared in 1.5-, 5-, and 16-month-old rats. Data show that metabolic responses vary with increase in age and experimental conditions. Dose-dependent decreases in plasma glucose (1.4 to 3.9 mumol/mL) and elevations in lactic acid (0.8 to 3.0 mumol/mL) were greater in 1.5- versus 16-month-old rats, were delayed in cannulated rats, and were preceded by hyperglycemia following larger IV doses. Plasma TG levels were elevated after TNF in all groups except precannulated rats, and also showed differences with age. In young rats, the elevation in TG peaked 2 hours after IP injection with return to baseline and was preceded by an elevation in FFA levels. In older rats, which were hypertriglyceridemic at base line, the elevation in TG by TNF occurred by suppressing the decrease in TG of controls, was not accompanied by an increase in FFA levels, was sustained for 5 hours, and was of greater magnitude than in young rats. Significant changes in plasma insulin did not occur in young and older rats after IV TNF. However, young rats had a significant decrease (P less than .02) in plasma insulin and an elevation in corticosterone levels after IP TNF, whereas older rats exhibited an increase in plasma insulin (P less than .02) and a comparable elevation in plasma corticosterone. Young rats also showed an increase in plasma insulin following IP TNF when hypoglycemia was prevented by the infusion of glucose. However, when insulin levels were held comparable (2.4 ng/mL), glucose uptake was enhanced (P less than .05) compared with controls. These findings indicate that mobilization of energy substrates occurs during the initial exposure to TNF, which is altered by the nutritional state of the rats and the dose and route of administration.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1518427 TI - Enhanced glutamine and glucose metabolism in cultured rat splenocytes stimulated by phorbol myristate acetate plus ionomycin. AB - Metabolism of glutamine and glucose was studied in normal rat splenocytes cultured for 48 hours in the presence and absence of a mixture of the mitogens, phorbol myristate acetate (PMA) + ionomycin (Iono). 3H-Thymidine uptake by splenocytes was stimulated more than 500-fold by PMA + Iono. After culture, cells were incubated for 2 hours in the presence of either 2 mmol/L [U-14C]glutamine +/ 5 mmol/L glucose or 5 mmol/L [U-14C]glucose +/- 2 mmol/L glutamine in Krebs Ringer HEPES buffer. Glutamine was metabolized mainly to ammonia, glutamate, aspartate, and CO2, and these products were all increased (P less than .01) by twofold to 2.5-fold in stimulated cells. Glucose was metabolized mainly to lactate and, to a lesser extent, to pyruvate and CO2. Lactate production from glucose was increased (P less than .01) by 2.4-fold in stimulated cells, without changes in pyruvate or CO2 production. In unstimulated, cultured splenocytes, glutamine was not quantitatively as important as glucose in the provision of adenosine triphosphate (ATP), as calculated on the basis of measured metabolites. However, in stimulated cells, glutamine became a much more important energy substrate, providing similar amounts of ATP to those from glucose. The oxidation of glutamine via the Krebs cycle was the major pathway for glutamine-derived ATP production, while lactate production from glucose accounted for the major part of glucose-derived ATP in PMA+Iono-stimulated splenocytes. Thus, we suggest glutamine plays a dual metabolic role in these cells, as both an important fuel and an essential source of carbon and nitrogen precursors for biosynthetic processes.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1518428 TI - Proceedings, Sandostatin, State of the Art. Monte Carlo, October 9-12, 1991. PMID- 1518429 TI - Gastroenteropancreatic endocrine tumors: effect of Sandostatin on tumor growth. The German Sandostatin Study Group. AB - One hundred fifteen gastroenteropancreatic (GEP) patients with malignant endocrine tumors entered a prospective multicenter trial (12 patients with gastrinoma, 53 with carcinoid syndrome, 45 with nonfunctioning tumors, and five with other endocrine GEP tumors) to determine the efficacy of 200 micrograms Sandostatin three times a day in the control of tumor growth. This interim report describes the results in 85 patients. Thirty-four patients died, 14 before and 20 after the first follow-up investigation, indicating a "negative" selection of patients included in the trial and suggesting that Sandostatin cannot prevent disease progress when it is far advanced. In the evaluation of 68 patients monitored for at least 3 months, partial regression was observed in 4.4%, stable disease in 50%, and tumor progression in 45%. However, an initially favorable response frequently occurred with a decrease in response later: 54.4% at 3 months to 38% at 12 months for the whole group of patients. Proven inhibition of tumor growth was mirrored by suppression of serum and urine hormone parameters. It is concluded that Sandostatin exerts a beneficial effect on tumor growth in patients with metastatic endocrine GEP tumors. This beneficial effect decreases with time and is as yet unpredictable in the individual patient. PMID- 1518430 TI - Pharmacodynamic effects of Sandostatin in the gastrointestinal tract. AB - Somatostatin (SST) is widely distributed throughout the human gastrointestinal system. There, it is found in neurons and fibers of both the submucosal and myenteric plexus and the pancreas, and also in the D cells of the stomach, gut, and pancreatic islets. Whereas in the intestinal nervous system, duodenum, and pancreas, somatostatin-14 (SST-14) appears to be the predominant molecular form, the endocrine-type D cells of the intestine primarily contain somatostatin-28 (SST-28). SST peptides may act very differently at different sites, as hormones, paracrine substances, or neurotransmitters. Because of this complexity of action, very little is known about the physiological effects of SST in the gastrointestinal tract. In contrast, the pharmacological actions of natural synthetic SST have been thoroughly studied and have given rise to many therapeutic applications. Octreotide, an analogue with a longer half-life and higher potency, has greatly facilitated the clinical application of SST. This review deals with the pharmacological effects of octreotide on different gastrointestinal functions. The SST analogue exerts a long-lasting inhibitory action on gastric acid, pancreatic enzyme, bicarbonate secretion, and on bile flow. It also inhibits stimulated intestinal secretion, ie, the release of neuropeptides from the gut and pancreas. It can also prolong orocecum transit time and prevent gallbladder contraction. It inhibits absorption of nutrients and exerts inhibitory effects on splanchnic hemodynamics. It is because of these actions that SST has attracted so much attention in the treatment of different gastrointestinal disorders. PMID- 1518431 TI - Endocrine applications of the somatostatin analogue octreotide (Sandostatin). PMID- 1518432 TI - The role of Sandostatin in acromegaly. AB - Long-acting somatostatin analogues are extensively used for the treatment of acromegalic patients who have not been cured by surgery or for whom surgery is contraindicated or hazardous. Such an analogue, Sandostatin, has been approved for this indication in various countries and to date an overall review is feasible. From the literature and our experience, clinical response of acromegaly is attained in 60% to 70%, with mainly a reduction in headaches, arthralgias, and acral growth. Hormonal response, evaluated on plasma growth hormone (GH) levels, is observed in more than 80% of the patients. In 36% to 45% of the patients, plasma GH levels are reduced to near-normal values, and in 50% of the patients, the percentage of reduction is greater than 50% of pretreatment values. The major source of concern is the occurrence of gallstones during the treatment; its frequency is evaluated differently. From the largest well-documented series, we retain a percentage of 12.5% of newly occurring cholelithiasis and in most cases they remain asymptomatic. Tumor shrinkage is minor in most cases. PMID- 1518433 TI - Long-term efficacy and tolerability of octreotide treatment in acromegaly. AB - Twenty-five acromegalic patients were studied during 6 years of treatment with octreotide, with a particular focus on the following parameters: (1) Administration schedule: in 10 patients, continuous subcutaneous (SC) octreotide infusion was compared with injections of octreotide at three dose levels (100, 250, and 1,500 micrograms/24 h) and was found to induce a greater and less fluctuating 24-hour growth hormone (GH) suppression. (2) Carbohydrate tolerance: average 24-hour blood glucose levels were unaffected by octreotide, regardless of administration schedule. Oral carbohydrate tolerance and intravenous (IV) glucose tolerance were unaffected by continuous octreotide infusion. However, octreotide injection given shortly before the tests reduced carbohydrate tolerance. (3) Thyroid function: octreotide and somatostatin acutely reduce the response of thyroid-stimulating hormone (TSH) to thyrotropin-releasing hormone (TRH). After a few days of treatment, it was demonstrated that octreotide slightly inhibits iodothyronine deiodination and induces a transient reduction in serum triiodothyronine (T3), rapidly compensated for by a persistent slight elevation of serum TSH. (4) Fat absorption was estimated as 24-hour fecal fat content and found to be in the same high-normal range before and after octreotide treatment. Vitamin K and D absorption were unaffected by octreotide. The incidence of gallstone formation was not greater than in the general Danish population, possibly due to the schedule used for octreotide injections. (5) Foot volume was regularly estimated and found to decrease with time, on average by 12% during the first 18 months.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1518434 TI - Presurgical octreotide treatment in acromegaly. AB - The aim of this study was to determine the role of octreotide administration in acromegalic patients as a preparation for selective adenomectomy using transsphenoidal route. Octreotide was administered for 3 to 6 weeks before surgery in 12 patients and for 4 to 39 months in 25 patients. The clinical response was judged as excellent or good in 10 of 12 patients from group I and in 23 of 25 patients from group II. Marked reduction (ie, greater than 50% of initial values) in serum growth hormone (GH) levels was seen in all patients, with levels to less than 5 micrograms/L in 68% of patients and less than 2 micrograms/L in 27%. Insulin-like growth factor 1 (IGF-1) levels decreased to within normal limits in half the cases. During long-term treatment, an escape phenomenon could be seen. Varying degrees of tumor shrinkage were seen in more than 50% of cases. During surgery, with regard to the relative ease or difficulty in removing the tumor, the consistency of the tumor and the separation of normal from pathological tissue, no significant difference was observed between patients given octreotide and those from control series. Morphological changes in adenomatous tissue were rather small. The surgical outcome was similar in the pretreated series as in the control series, except in enclosed adenomas, which showed a tendency to a higher success rate. Since octreotide improves both the clinical condition and hormonal parameters and induces varying degrees of tumor shrinkage, it is potentially useful as an adjunct to surgery. Morphological data suggest that octreotide exercises a functional inhibitory effect on GH release. PMID- 1518435 TI - Treatment of thyroid-stimulating hormone-secreting adenomas with octreotide. AB - From data collected in the literature, the effects of octreotide therapy in 37 patients with thyroid-stimulating hormone (TSH)-secreting adenomas who received short-term (1 to 2 weeks, n = 23) and long-term treatment (3 to 36 months) are reviewed. In 20 of 21 patients studied, short-term administration of octreotide (50 or 100 micrograms subcutaneously [SC] produced a 25% to 100% (mean +/- SD, 55.3% +/- 29%) decrease in TSH levels, with the nadir being obtained between the third and sixth hour following injection. After 1 to 2 weeks therapy with 50 to 100 micrograms twice or three times a day, 21 of 23 patients studied demonstrated a 66% (+/- 30%) decrease in TSH levels and 14 of 16 showed a 64% (+/- 27%) decrease in alpha-subunit levels. In approximately two thirds of the patients, the response was better than after short-term administration. The effect of octreotide on clinical and biological thyroid status was significant in all patients studied. After 1 week or 1 month of treatment, thyroid hormone levels were reduced in all patients and were normalized in 78%. Response to therapy was similar whether TSH secretion was pure or mixed (growth hormone [GH]-TSH adenomas). Fourteen patients received long-term treatment (3 to 36 months; mean, 12 +/- 10) with daily doses ranging from 200 to 1,500 micrograms. The response was better than or similar to that with short-term treatment. An escape occurred in TSH levels in two patients and in thyroid hormone levels in three patients, leading to an adjustment of dose or frequency of injection.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1518436 TI - Octreotide and diabetes: theoretical and experimental aspects. AB - Diabetes is characterized by paradoxical hypersomatotropinemia and hyperglucagonemia. The latter appears to enhance the tendency in imperfect metabolic control to reduce nitrogen balance, and the former appears to accelerate the deterioration of carbohydrate and lipid metabolism, and also to induce peripheral insulin resistance and hyperinsulinemia. In addition to direct metabolic effects, increasing evidence points to an association between hypersomatotropinemia and a number of metabolically dependent, characteristic functional abnormalities linked to the development of late diabetic manifestations. These include increased capillary fragility, lipid and hemostatic aberrations, tissue hyperperfusion, including increased cardiac output and renal plasma flow, and kidney hypertrophy. In theory, octreotide's actions could reduce these aberrations, and, in fact, this has been confirmed in recent experimental trials. PMID- 1518437 TI - Preliminary results with Sandostatin nasal powder in acromegalic patients. AB - This report details the first half of a double-blind, crossover sequence (Latin square) study of local and hormonal effects of nasally insufflated Sandostatin compared with those of subcutaneously injected Sandostatin. Nine of the planned 16 patients have been studied. They received a single application of 0.5, 1.0, and 2.0 mg Sandostatin as nasal powder and 0.1 mg by subcutaneous (SC) injection. The results indicate that absorption from the nasal epithelium occurs after approximately 10 minutes and comprises approximately 20% of the dose administered. This indicates that peak serum Sandostatin values occur very rapidly, ie, 10 minutes after application. After approximately 2 hours, the serum disappearance rates are similar to those obtained after SC injection. The suppressive effect on serum growth hormone (GH) levels is equal with the two forms of application and suggests that future clinical treatment with an intranasal application of 0.5 mg thrice daily is feasible. No side effects were noted apart from an immediate swelling of nasal mucosa, which receded gradually over the following 2 hours. This was either unnoticed or considered insignificant by the patients and will probably be deemed harmless by the rhinologist in eventual long-term clinical trials. PMID- 1518438 TI - Effects of the somatostatin analogue, octreotide, in polycystic ovary syndrome. AB - In view of the association of hyperinsulinemia with elevated luteinizing hormone (LH) levels and hyperandrogenism in polycystic ovary syndrome (PCOS), the effect of octreotide was investigated in women with PCOS. Twelve amenorrheic women were treated with 100 micrograms octreotide twice a day for 7 days; 13 infertile women unresponsive to clomiphene citrate were treated either with octreotide (100 micrograms twice a day from day 1 of the menstrual cycle until corpus luteum formation) in addition to human menopausal gonadotropins (HMG) or with HMG alone. Octreotide significantly reduced the 4-hour integrated LH concentrations. LH pulse amplitude and nadir concentrations, and LH, testosterone, androstenedione, and estradiol responses to a gonadotropin-releasing hormone (GnRH) analogue in amenorrheic PCOS women. Octreotide treatment also resulted in a more "appropriate" hormonal milieu at the time of human chorionic gonadotropin (HCG) injection in the infertile women, with LH and testosterone levels being reduced while follicle-stimulating hormone (FSH) levels increased. Orderly follicular growth occurred, with one or two mature follicles being present at the time of HCG injection in cycles in which octreotide was given together with HMG. There were no cases of hyperstimulation, even in women who had previously hyperstimulated after HMG alone. Octreotide thus inhibits LH and androgen secretion and may improve ovulatory performance in infertile women with PCOS. PMID- 1518439 TI - Proceedings of the discussion, "Tolerability and safety of Sandostatin". AB - Side effects of octreotide may be local, biochemical, gastroenterological, or endocrinological. Local pain at the injection site occurs frequently, but rarely lasts more than 15 minutes and often resolves with continued therapy and may be improved if the vial is warmed prior to injection. No long-term hematological or biochemical abnormalities have been described. Despite initial diarrhea in some patients, no change in circulating fat-soluble vitamins has been consistently reported. Antibodies to octreotide have been described, but are rare. Abdominal pain or diarrhea can occur at the beginning of therapy. These symptoms rarely persist and are minimal if the injections are timed between meals, but this may increase the incidence of gallstones. Gallstones occur with increased frequency. Gastritis has been described as being an invariable consequence of long-term treatment with octreotide. We have found the incidence to be increased in patients on octreotide, but this is not invariable. Hypoglycemia may be exacerbated in some patients with insulinoma because of glucagon suppression. Small numbers of patients on octreotide for acromegaly have developed hypoglycemic. Conversely, carbohydrate tolerance may temporarily worsen because of insulin suppression and rarely oral hypoglycemia drug therapy may become necessary. Most frequently, carbohydrate tolerance does not deteriorate. In some patients with acromegaly, pituitary tumor size may continue to increase despite continued therapy. Last, there is the theoretical risk of addiction to a compound which may act through opiate receptors and considerably alleviates headache in some patients with pituitary tumor. Overall, despite the multiplicity of theoretical side effects, the majority of patients tolerate octreotide well, with no serious untoward effects. PMID- 1518440 TI - Proceedings of the workshop, "Practical approaches to the diagnosis and treatment of acromegaly". AB - Practical approaches to the management of acromegaly are discussed. The roles of surgery, radiotherapy, and medical treatment with oral dopamine agonists such as bromocriptine or the long-acting somatostatin analogue octreotide given subcutaneously are reviewed. Most cases need surgery, but cure is rare in patients with macroadenomas, although common with microadenomas. Radiotherapy should be considered in surgical failures, but takes several years to be effective. Medical treatment with octreotide is effective in the majority, for whom it represents a major advance, but it needs to be administered subcutaneously and the development of gallstones and gastritis in long-term treatment are problems. Bromocriptine is usually less effective, but occasionally still plays a role in the therapeutic program. Combinations of the different modalities are usually required in the management of acromegalic patients. PMID- 1518441 TI - Potential indications for octreotide in endocrinology. AB - Treatment with Sandostatin is established in acromegaly, thyroid-stimulating hormone (TSH)-producing pituitary, and endocrine-active gastroenteropancreatic tumors. Potential indications include ectopic hormone syndromes, medullary thyroid carcinomas, pituitary resistance to thyroid hormones, tall stature children, diabetes mellitus and diabetic complications, polycystic ovary syndrome, and Graves' ophthalmopathy. Particularly in the ectopic growth hormone releasing hormone (GHRH) syndrome, Sandostatin is unequivocally effective and, in the ectopic corticotropin syndrome selected cases can be treated successfully with Sandostatin, leading to marked clinical improvement. In many of the above situations, only subgroups show a response to Sandostatin, which may be identified by scintigraphy with labeled Sandostatin. This pertains also to Graves' ophthalmopathy, for which Sandostatin may be particularly promising and where positive and negative Sandostatin scans have been demonstrated. However, for all these potential indications, larger, well-studied series are needed, before definitive conclusions can be drawn. PMID- 1518442 TI - DNA structures. Part B. Chemical and electrophoretic analysis of DNA. PMID- 1518443 TI - Two-dimensional gel electrophoresis of circular DNA topoisomers. PMID- 1518444 TI - Topological structure of DNA knots and catenanes. PMID- 1518445 TI - Probes of DNA structure. PMID- 1518446 TI - Probing DNA structure with osmium tetroxide complexes in vitro. PMID- 1518447 TI - Detection of non-B-DNA structures at specific sites in supercoiled plasmid DNA and chromatin with haloacetaldehyde and diethyl pyrocarbonate. PMID- 1518448 TI - Hydroxylamine and methoxylamine as probes of DNA structure. PMID- 1518449 TI - Mapping adducts of DNA structural probes using transcription and primer extension approaches. PMID- 1518450 TI - DNA bending, flexibility, and helical repeat by cyclization kinetics. PMID- 1518451 TI - Analyzing DNA curvature in polyacrylamide gels. PMID- 1518452 TI - Probing of DNA structure in cells with osmium tetroxide-2,2'-bipyridine. PMID- 1518453 TI - Analysis of DNA structure in vivo using psoralen photobinding: measurement of supercoiling, topological domains, and DNA-protein interactions. PMID- 1518454 TI - Topological approaches to studies of protein-mediated looping of DNA in vivo. PMID- 1518455 TI - Assay of anti-DNA antibodies. PMID- 1518456 TI - Algorithms for prediction of histone octamer binding sites. PMID- 1518457 TI - Thermodynamics of ligand-nucleic acid interactions. AB - Ligand-and protein-DNA equilibria are extremely sensitive to solution conditions (e.g., salt, temperature, and pH), and, in general, the effects of different solution variables are interdependent (i.e., linked). As a result, an assessment of the basis for the stability and specificity of ligand-or protein-DNA interactions requires quantitative studies of these interactions as a function of a range of solution variables. Many of the most dramatic effects on the stability of these interactions result from changes in the entropy of the system, caused by the preferential interaction of small molecules, principally ions which are released into solution on complex formation. A determination of the contributions of these entropy changes to the stability and specificity of protein-and ligand DNA interactions requires thermodynamic approaches and cannot be assessed from structural studies alone. PMID- 1518458 TI - Nonspecific ligand-DNA equilibrium binding parameters determined by fluorescence methods. PMID- 1518459 TI - Global features of DNA structure by comparative gel electrophoresis. PMID- 1518460 TI - Loracarbef. PMID- 1518461 TI - Influenza vaccine, 1992-1993. PMID- 1518462 TI - Automatic verification of radiation field shape using digital portal images. AB - Two computer methods for matching digital line drawings have been tested for automatic on-line verification of the radiation field shape during radiotherapy. This work is part of a research program aiming at automated inspection of on-line acquired digital portal images. Both methods, moment normalization and point distance minimization, compare the field edge detected in the portal image with the intended field edge and the beam shaping devices marked in the simulator image. Tests showed that the methods should be used together. First, shape deviations in the detected field edge are classified quickly, in less than a second (25 MHz 386 + 387 PC), as large (e.g., missing blocks) or small (e.g., shifts of a few mm) by moment normalization. Then the portal image is mapped to the simulator image by field edge alignment with a translation and magnification obtained from moment normalization and a rotation from point distance minimization. The mapped portal image and the simulator image juxtaposed on a monitor screen for visual inspection. Finally, the small field shape deviations are detected by an analysis of the relationship between the radiation field shape and the positioning of field shaping devices using point distance minimization. PMID- 1518463 TI - Charge-coupled device detector: performance considerations and potential for small-field mammographic imaging applications. AB - The physical characteristics of a charge-coupled device (CCD) image detector were evaluated, as well as its potential as a digital imaging device for small field mammographic applications such as preoperative needle localization. The detection system is based on a 2048 x 2048 pixel CCD operated in 1024 x 1024 mode. The CCD was optically coupled to an intensifying screen via a lens, without intermediate intensification. The thermal noise was suppressed to 0.15 electrons pixel-1s-1 by cooling the CCD with liquid nitrogen. The dominant source of noise was attributed to the on-chip amplifier during the readout process that was performed at 50,000 pixels s-1. The measured readout noise level was 15 electrons per pixel. The low noise characteristics of this CCD prototype detector produced encouraging results under conditions simulating mammography, with a signal level close to one electron per pixel for each detected x ray. The mean glandular dose to the breast, based on the entrance exposure measured from a standard mammographic phantom would be 1.52 mGy (152 mrad). The ultimate spatial resolution of the system was approximately 8 cycles/mm but it was limited to about 5 cycles/mm when operated in the 1024 x 1024 imaging mode. Other physical characteristics of the system such as optical coupling efficiency, exposure response, and signal-to noise ratio were evaluated. The results of this study suggest that the use of a scientific-grade CCD allows for very good low-contrast discrimination and moderate spatial resolution under conditions simulating mammography, but the current prototype is limited to a 9 x 9-cm2 field of view.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1518464 TI - Precision in quantitative CT: impact of x-ray dose and matrix size. AB - A study was performed to determine whether recommended technique factors for postprocessing dual-energy (DE) quantitative computed tomography are optimum in terms of precision and x-ray dose. In particular, possible dose reduction as a result of an upgrade of the CT scanner to more efficient detectors was explored. Series of images of an anthropomorphic phantom containing a human vertebra, a tissue-simulating lumbar simulator with various marrow inserts, and a polyethylene cylinder were generated. Recommended DE x-ray technique factors as well as factors resulting in about two times, one-half, and one-fourth the x-ray dose were employed. The effects of reconstruction with different matrix sizes was studied. Standard deviations of the CT numbers within regions of interest in individual images (noise) and standard deviations of mean CT numbers, single energy (SE), and DE measurements for series of images (reproducibilities) were computed. It was found that the low-energy component of the DE technique was optimum, but the high-energy component could be reduced by a factor of 2 with negligible loss in precision. This translates into a dose reduction of 36% relative to the recommended DE technique. Vertebral inhomogeneities were responsible for more than 65% of the standard deviations in individual images of the vertebra even at the lowest doses. For all of the techniques, the noise in images of all objects decreased as the x-ray dose increased and as the matrix size decreased. Reproducibility of mean values, however, did not necessarily improve, and aberrant results such as improvement in reproducibility with a reduction in dose were sometimes observed. It is hypothesized that this may be due to variations in the actual kVp for each image in a series. PMID- 1518465 TI - Signal and noise in modulation transfer function determinations using the slit, wire, and edge techniques. AB - The modulation transfer function (MTF) of an idealized imaging system can be determined from the Fourier transform of the system's line-spread function (LSF). Three techniques of experimentally determining the LSF require imaging either a slit, wire, or edge. In this paper, these three techniques are modeled theoretically to determine the noise in the calculated MTFs as a function of spatial frequency resulting from both quantum fluctuations and stochastic detector noise. The techniques are compared using the signal-to-noise ratio (SNR) in the MTF, defined as the ratio of the MTF value to the standard deviation in an ensemble of MTF determinations from independent measurements. It is shown that for a specified photon fluence, the edge method MTF has the highest SNR at low spatial frequencies, while that of the slit method is superior at high frequencies. The wire method SNR is always inferior to that of the slit technique. This suggests that the edge method is preferable for measuring parameters such as the low-frequency drop, and the slit method is preferable for determining high-frequency response. The cross-over frequency at which the slit and edge methods are equal (f(e)) for quantum-noise limited systems is a function of the slit width and the length over which the LSF is measured. For detector noise limited systems, f(e) is dependent on the slit width only. The SNR in all but the quantum-noise limited slit method can therefore be increased by decreasing the length over which the LSF is measured, smoothing the tails of the LSF, or by fitting the tails to an analytic expression. PMID- 1518466 TI - A multiple projection method for digital tomosynthesis. AB - A new method of optimized efficiency for the retrospective reconstruction of tomograms is presented. The method has been developed for use with isocentric fluoroscopic units and is capable of performing digital tomosynthesis of anatomical planes of user selected orientation and distance from the isocenter. Optimization of efficiency has been achieved by segmenting the reconstruction process into discrete transformations that are specific to groups of pixels, rather than performing pixel by pixel operations. These involve a number of projections of the acquired image matrices as well as parallel translations and summing. Application of this method has resulted in a significant reduction of computing time. The proposed algorithm has been experimentally tested on a radiotherapy simulator unit with the use of a phantom and the obtained results are reported and discussed. PMID- 1518467 TI - Selection of fat-equivalent materials in postprocessing dual-energy quantitative CT. AB - Postprocessing dual-energy QCT is supposed to be able to predict the bone mineral more accurately than single-energy QCT. In addition, the fat content in the vertebral body can be determined. To this aim, some methods include fat equivalent materials in the calibration device. However, the choice of an appropriate fat-equivalent material is difficult. To solve this selection problem, a method has been developed in which the x-ray interactions of tissue are characterized by three energy-independent parameters. For five different known constituents of anatomical fat, fat-equivalent materials are evaluated. It is shown that it is not possible to find one fat-equivalent material for all anatomical fat compositions. For this reason, the influence of a mismatch between the characterization parameters of anatomical fat compositions and fat-equivalent materials has been evaluated. It is shown that a mismatch in tissue characterization parameters can result in deviations of 10% in the bone mineral content and more than 300% in the estimated fat contents. PMID- 1518468 TI - Nonlinear filters applied on computerized axial tomography: theory and phantom images. AB - New nonlinear image processing techniques, in particular smoothing based on the understanding of the image, may create computerized tomography (CT) images of good quality using less radiation. Such techniques may be applied before the reconstruction and particularly after it. Current CT scanners use strong linear low-pass filters applied to the CT projections, reducing noise but also deteriorating the resolution of the image. The method in this study was to apply a weak low-pass filter on the projections, to perform the reconstruction, and only then to apply a nonlinear filter on the image. Various kinds of nonlinear filters were investigated based on the fact that the image is approximately piecewise constant. The filters were applied with many values of several parameters and the effects on the spatial resolution and the noise reduction were evaluated. The signal-to-noise ratio of a high-contrast phantom image processed were compared with the nonlinear filter, with the SNR of the phantom images obtained with the built-in CT linear filters in two scanning modes, the normal and the ultra high resolution modes. It was found that the nonlinear filters improve the SNR of the image, compared to the built-in filters, about three times for the normal mode and twice for the UHR scanning mode. The most successful filter on low-contrast phantom image was applied and it also seems to lead to promising results. These results seem to show that applying nonlinear filters on CT images might lead to better image quality than using the current linear filters.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1518469 TI - X-ray imaging using amorphous selenium: determination of x-ray sensitivity by pulse height spectroscopy. AB - There is a renewed interest in the application of photoconductors especially amorphous selenium (a-Se) to x-ray imaging. A new method for evaluating W +/-, the energy absorption necessary to release an electron-hole pair in a-Se is described. All previous methods used for the evaluation of the x-ray sensitivity of a-Se measure a change in surface potential on a charged plate due to irradiation by x rays. This results in a measurement of W +/- and other factors in combination. These factors include the energy absorbed from the spectrum of irradiating x rays and the a-Se layer capacitance. Such indirect methods are prone to error. A direct method for the evaluation of W +/-, which is based on the pulse height spectra resulting from the absorption of individual monoenergetic x-ray photons in a-Se, has been developed. PMID- 1518470 TI - Direct digitization of optical images using a photostimulable phosphor system. AB - The authors describe a method for directly digitizing optical images with a photostimulable phosphor (PSP) system. A PSP plate is initially charged with an exposure to a uniform x-ray field, and is then exposed to an optical image which discharges the plate in relation to the amount of incident light. Two applications were investigated: a contact-print technique for digitizing film radiographs, and a projection technique for digitizing transparent objects such as histology slides. Spatial uniformity was found to be adequate, and linearity of optical density response was excellent from 0.0-2.9 o.d. after look-up table correction. Spatial frequency response was degraded with the optical technique relative to the x-ray imaging properties of the plates, but was restorable by Fourier filtering. Image noise following spatial enhancement was satisfactory at intermediate to high optical densities using a high-resolution PSP plate, but was somewhat degraded at low densities. PMID- 1518471 TI - Evaluating the spatial resolution performance of a time-resolved optical imaging system. AB - An imaging system is being developed as a possible means of screening for breast cancer using harmless doses of visible or near-infrared radiation. This system produces transmission images of highly scattering objects by recording and discriminating between the times-of-flight of transmitted photons. Experiments have been performed to evaluate the likely spatial resolution performance of such a system. This involved measuring the edge profile produced by an opaque mask embedded in a highly scattering medium, and evaluating the spatial resolution as a function of the period of time over which transmitted light was integrated. The results suggest that a resolution of a few millimeters is achievable with a system with a temporal resolution of about 10 ps. PMID- 1518472 TI - Human exposure to 4.0-Tesla magnetic fields in a whole-body scanner. AB - Details are given for the design, construction, properties, and performance of a large, highly homogeneous magnet designed to permit whole-body magnetic resonance imaging and spectroscopy at 4 T. The magnet has an inductance of 1289 H and a stored energy of 33.4 MJ at rated field. The health of a group of 11 volunteers who had varying degrees of exposure to this field was followed over a 12-month period and no change that could be associated with this exposure was detected. A mild level of sensory experiences, apparently associated with motion within the field of the magnet, was reported by some of the volunteers during some of their exposures. A questionnaire regarding sensory effects associated with magnetic resonance scanners and possibly caused by the static magnetic field of these instruments, was given to nine respondents who had experience within both 1.5-T scanners and this 4-T scanner and to another group of 24 respondents who had experience only within 1.5-T scanners. For the sensations of vertigo, nausea, and metallic taste there was statistically significant (p less than 0.05) evidence for a field-dependent effect that was greater at 4 T. In addition, there was evidence for motion-induced magnetophosphenes caused by motion of the eyes within the static field. These results indicate the practicality of experimental whole body body scanners operating at 4 T and the possibility of mild sensory effects in humans associated with motion within a static magnetic field. The results also indicate the likelihood of a wide margin of safety for the exposure of noncompromised patients to the static fields of conventional magnetic resonance scanners operated at 1.5 to 2 T and below. PMID- 1518473 TI - Mapping of the radio frequency magnetic field with a MR snapshot FLASH technique. AB - A fast method to measure the radio frequency magnetic field intensity distribution during magnetic resonance examinations within objects or patients is proposed. Using a snapshot FLASH sequence, several images are obtained with different transmitter amplitudes for the single prepulse prior to the imaging sequence. The signal intensity at each pixel within a selected slice is diminished by this prepulse, unless the pulse angle is 0 degrees or a multiple of 360 degrees. This condition can be used to measure that transmitter amplitude Umax for each pixel which causes an excitation of 360 degrees by the prepulse. The values of Umax can be visualized in an image and are inversely proportional to the radio frequency magnetic field strength at each position within the image. The method can also be used for in-vivo measurements, where it may be difficult to realize prepulses with sufficient high flip angles. In these cases, signal corresponding to a 180 degree prepulse can be used for calculating Umax. PMID- 1518474 TI - The effect of intrinsic attenuation correction methods on the stationarity of the 3-D modulation transfer function of SPECT. AB - The application of stationary restoration techniques to SPECT images assumes that the modulation transfer function (MTF) of the imaging system is shift invariant. It was hypothesized that using intrinsic attenuation correction (i.e., methods which explicitly invert the exponential radon transform) would yield a three dimensional (3-D) MTF which varies less with position within the transverse slices than the combined conjugate view two-dimensional (2-D) MTF varies with depth. Thus the assumption of shift invariance would become less of an approximation for 3-D post- than for 2-D pre-reconstruction restoration filtering. SPECT acquisitions were obtained from point sources located at various positions in three differently shaped, water-filled phantoms. The data were reconstructed with intrinsic attenuation correction, and 3-D MTFs were calculated. Four different intrinsic attenuation correction methods were compared: (1) exponentially weighted backprojection, (2) a modified exponentially weighted backprojection as described by Tanaka et al. [Phys. Med. Biol. 29, 1489 1500 (1984)], (3) a Fourier domain technique as described by Bellini et al. [IEEE Trans. ASSP 27, 213-218 (1979)], and (4) the circular harmonic transform (CHT) method as described by Hawkins et al. [IEEE Trans. Med. Imag. 7, 135-148 (1988)]. The dependence of the 3-D MTF obtained with these methods, on point source location within an attenuator, and on shape of the attenuator, was studied. These 3-D MTFs were compared to: (1) those MTFs obtained with no attenuation correction, and (2) the depth dependence of the arithmetic mean combined conjugate view 2-D MTFs.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1518475 TI - A pseudo-Poisson noise model for simulation of positron emission tomographic projection data. AB - Although radioactive decay obeys Poisson statistics, because of the corrections that are applied to the projection data prior to reconstruction, the noise in positron emission tomography (PET) projections does not follow a Poisson distribution. Use of Poisson noise when simulating PET projections in order to test the performance of reconstruction and processing techniques is therefore not appropriate. The magnitude of PET projection noise was observed to be as much as 10 to 100 times greater than Poisson noise in some instances. A quadratic function was found to fit the relationship between noise power spectral density and total projection count. The coefficients of the quadratic function were determined for projections of different tracer distributions and types. Using these observations, a method of simulating PET projections was developed based on a pseudo-Poisson noise model. Projections simulated according to this method are good approximations to real projection data and take into account the characteristics of individual PET cameras and particular tracer distributions. Such simulated projections have been valuable in predicting the performance of reconstruction algorithms. This approach can also be applied to single photon emission tomography. PMID- 1518476 TI - A diffusion theory model of spatially resolved, steady-state diffuse reflectance for the noninvasive determination of tissue optical properties in vivo. AB - A model based upon steady-state diffusion theory which describes the radial dependence of diffuse reflectance of light from tissues is developed. This model incorporates a photon dipole source in order to satisfy the tissue boundary conditions and is suitable for either refractive index matched or mismatched surfaces. The predictions of the model were compared with Monte Carlo simulations as well as experimental measurements made with tissue simulating phantoms. The model describes the reflectance data accurately to radial distances as small as 0.5 mm when compared to Monte Carlo simulations and agrees with experimental measurements to distances as small as 1 mm. A nonlinear least-squares fitting procedure has been used to determine the tissue optical properties from the radial reflectance data in both phantoms and tissues in vivo. The optical properties derived for the phantoms are within 5%-10% of those determined by other established techniques. The in vivo values are also consistent with those reported by other investigators. PMID- 1518477 TI - Calibration of parallel-plate chambers: resolution of several problems by using Monte Carlo calculations. AB - For five commonly used parallel-plate ion chambers, Monte Carlo calculations are presented of the wall attenuation and scatter correction factors (Kwall = Awall-1 or katt-1) and the correction for nonhomogeneous composition of the chamber (Kcomp or related to km). The chambers are assumed to have 0.5 g/cm2 buildup caps made of the predominant material in each chamber. These correction factors are needed if air-kerma calibration factors are used to deduce the chamber's cavity gas calibration factor, Ngas. The scatter from the material around the cavity more than compensates for the attenuation in the front wall and hence Kwall values are less than unity. The corrections for the nonhomogeneous composition can be significant. Thin collectors or insulators behind the collecting volume can have a major effect because electron backscattering depends strongly on material. The calculations agree well with experimental data and explain previous results that had not been understood. Calculations for different buildup caps predict trends in chamber in-air responses, which go in the opposite direction to the km values for homogeneous chambers of the same materials. It is argued that Pwall, the wall correction factor for photon-beam measurements in-phantom is, to first order, the same correction factor as Kcomp, calculated for a buildup cap of the same material as the phantom material and the initial assumption that the wall material is made of the same material. Hence, Pwall can also be significantly different from unity. Recommended values of kmkatt or the equivalent Ngas/Nx, and Pwall (in 60Co beams) are presented for the 5 chambers. These values treat the Exradin P11, Markus and Holt parallel-plate chambers as homogeneous in construction whereas the values for the NACP and Capintec PS-033 chambers demonstrate that the chambers are distinctly nonhomogeneous. PMID- 1518478 TI - An analysis of equivalent fields for electron beam central-axis dose calculations. AB - The concepts of the equivalent square or circular field have long been used in dose calculations for photon beams. These concepts allow data measured for square or circular fields to be extended to calculate, for example, the percentage depth doses or output factors of rectangular or irregular fields. It has been pointed out in the past that an electron beam equivalent field dimension varies with depth and, thus, will have questionable utility. As the equivalent square and circle have proven to be useful in photon beam dose calculations, the work described in this paper has sought to analyze conditions under which equivalent fields may be useful for electron beam dose calculations. Equivalent square field dimensions and circular field radii are derived using the Fermi-Eyges theory and are compared to a number of approximate equivalent fields that have been applied to electron dose calculations. Calculations are also compared with measurements presented in the literature. It is shown that the accuracy of an electron dose calculation using these approximate equivalent fields diminishes with a decreasing degree of lateral scatter equilibrium at the central axis and only becomes accurate once equilibrium is established. As the central-axis dose under this latter condition is in any event independent of field shape or size, the equivalent field approach becomes unnecessary. Because of this and other restrictions discussed, it is concluded that the equivalent fields analyzed here should not be used for electron beam dose calculations. PMID- 1518479 TI - A convolution method for calculating 10-MV x-ray primary and scatter dose including electron contamination dose. AB - This paper has improved some of the weak points appearing in a previous article [A. Iwasaki, Med. Phys. 17, 203-211 (1990)] dealing with the calculation of 10-MV x-ray primary and scatter dose. The main improved points are as follows: (i) A pair of new functional equations expressing the primary dose spread array has been yielded. Consequently, the accuracy of the primary dose calculation both in the aluminum layer and in the soft tissue layer beyond the aluminum has been improved. (ii) A new functional equation expressing the backscatter factor has been developed. It has been utilized in the differential backscatter factor equation. Consequently, the calculated scatter dose spread array has been improved. (iii) A method of calculating the dose due to electron contamination has been introduced. With respect to the primary dose, the primary plus scatter dose, and the primary plus scatter plus electron contamination dose, it has been shown how the depth of maximum dose (dmax) varies with field size. PMID- 1518480 TI - Higher energy: is it necessary, is it worth the cost for radiation oncology? AB - The physical characteristics of the interactions of megavoltage photons and electrons with matter provide distinct advantages, relative to low-energy (orthovoltage) x rays, that lead to better radiation dose distributions in patients. Use of these high-energy radiations has resulted in better patient care, which has been reflected in improved radiation treatment outcome in recent years. But, as the desire for higher energy radiation beams increases, it becomes important to determine whether the physical characteristics that make megavoltage beams beneficial continue to provide a net advantage. It is demonstrated that, in fact, there is an energy range from 4 to 15 MV for photons and 4 to 20 MeV for electrons that is optimally suited for the treatment of cancer in humans. Radiation beams that exceed these maximum energies were found to add no advantage. This is because the costs (price of unit, installation, maintenance, shielding for neutron and photons) are not justified by either improved physical characteristics of the radiation (penetration, skin sparing, dose distribution) or treatment outcome. In fact, for photon beams some physical characteristics result in less desirable dose distributions, less accurate dosimetry, and increased safety problems as the energy increases for example, increasingly diffuse beam edges, loss of electron equilibrium, uncertainty in dose perturbations at interfaces, increased neutron contamination, and potential for higher personnel dose. The special features that make electron beams useful at lower energies, for example, skin sparing and small penetration, are lost at high energies. These physical factors are analyzed together with the economic factors related to radiation therapy patient care using megavoltage beams. PMID- 1518481 TI - Photon spectral characteristics of a new double-walled iodine-125 source. AB - The photon spectral characteristics of a recently designed Iodine-125 source have been measured. The source has a physical length of 5 mm and a diameter of 0.8 mm. A thin tungsten filament coated with radioactive Iodine-125 is used as a radiographic marker and is encapsulated in a double wall titanium shell of uniform thickness all around. The photon spectral characteristics, measured with an intrinsic germanium (Ge) detector coupled to a multichannel analyzer, reveal that the seed emits the 27.4-keV K alpha and 31.4-keV K beta x rays and 35.5-keV gamma photons from the decay of Iodine-125. Because of their low energy, the tungsten x rays are not observed in the spectrum. The anisotropy of the radiation fluence for each of the above-mentioned photon energies was measured in planes containing the seed short and long axes. The 4 pi-averaged anisotropy factor for the total radiation fluence, i.e., sum of the above three photon energies is 0.92. The photon intensity radiated along the seed long axis is approximately equal to the intensity in the seed transverse direction due to the absence of end welds. The new Iodine-125 source is characterized by good radiographic visualization, greater structural strength due to double wall encapsulation design, and emission of more isotropic Iodine-125 photon spectrum. PMID- 1518482 TI - Clinically relevant optimization of 3-D conformal treatments. AB - In this paper a method of computer-aided optimization of 3-D conformal treatment plans is presented which incorporates models to predict the clinical consequences of resulting dose distributions. Even though these models are simplistic, it is submitted that their intelligent use leads to treatment plans which indicate lower normal tissue complications and higher tumor control. Dose distribution data, biological models, and observed normal tissue and tumor response data are used to compute tumor control and normal tissue complication probabilities for each of the critical normal structures encountered in a treatment plan. These quantities are combined into a single score using an objective function which incorporates the importance of each end point as assessed by the physician. Using the "simulated annealing" method of optimization, the beam weights are adjusted to maximize the score. Additional constraints are applied to ensure consistency of the results of optimization with the judgment of the physician. These optimization methods have been applied to conformal treatment plans consisting of multiple fixed fields with conformal field shaping. The results indicate that the methods presented have considerable potential. PMID- 1518483 TI - A model for computer-controlled delivery of 3-D conformal treatments. AB - Three-dimensional conformal radiation treatments are highly complex and may comprise a large number of coplanar and noncoplanar beams, virtually all of which are shaped and may also employ arbitrary intensity modulation. The delivery of such treatments with conventional means is highly labor intensive and limited to a relatively small number of fields. A generalized model for a system that can deliver 3-D conformal treatments rapidly and safely using a computer-controlled treatment machine equipped with a multileaf collimator is presented. The model emphasizes the separation of tasks between an external computer programmed by the user institution and a control computer proprietary to the treatment machine manufacturer. The treatment scheme that is employed consists of a sequence of fixed fields, called segments, which are delivered in succession without human intervention. Settings for all segments, derived from a 3-D conformal treatment planning system, are downloaded by the external computer into the control computer of the treatment machine. During patient setup, the control computer enables the operator to step through computer-controlled setup of the segments without radiation to ensure the absence of collisions, and to allow the adjustment of setup parameters if necessary. The external computer verifies the treatment setup and permits the control computer to carry out the treatment segment by segment. Safety aspects of the model and anomalous situations which may arise are discussed. PMID- 1518484 TI - Optimization of brachytherapy dose distributions by simulated annealing. AB - An algorithm based on the method of simulated annealing is presented for optimizing brachy-therapy dose distributions. The algorithm accommodates either static configurations of multiple sources or single stepping sources, hence in principle can be used to optimize both low- and high-dose rate treatments delivered with remote afterloading equipment. Required inputs include the specification of target dose rates and dose rate limits, expressed in absolute or relative terms, at operator selected points near the treatment site. The influence of the dose rate limits can be adjusted continuously through the use of one or more penalty factors. The algorithm generates a set of integer weights, one for each available source position, which are interpreted in terms of configuration occupancy numbers for static source arrangements and relative dwell times for stepping sources. Application is made to several variations of a hypothetical low-dose rate vaginal vault planning problem involving one rectal and six applicator calculation points. The algorithm's performance for different source strengths, annealing schedules, target dose rates, dose rate limits, and values of a single penalty factor lambda was examined. With a simple annealing schedule and value of lambda = 25, the algorithm found solutions of high quality for all problem variants. The CPU time required for optimization on a Vax 11/750 computer ranged from 2 min for a single configuration to 25 min for a solution consisting of four configurations. These results support the use of simulated annealing for clinical planning of low dose rate vaginal treatments, and encourage investigation of other applications in brachytherapy. PMID- 1518485 TI - Rapid dose calculations for stereotactic radiosurgery. AB - A three-dimensional dose calculation algorithm is described for stereotactic radiosurgery using multiple noncoplanar beam arcs. Precalculated dose libraries of 20-deg arc segments, or mini arcs, are stored in computer memory which permits rapid calculation of complete, high resolution, three-dimensional isodose distributions and dose volume histograms. Three-dimensional patient contours and target volumes are obtained from CT scans and angiographic x rays. Rapid dose calculations are made possible by the use of arc libraries and an improved algorithm for mapping beam doses to the dose calculation grid. This permits more flexibility in designing optimum treatment plans, as five-six complete plans can be generated in less than 1 h. Thus many possible treatment options can be tested in the 3-4-h time period typically available in stereotactic procedures between CT scanning and treatment. PMID- 1518486 TI - Optimized dynamic rotation with wedges. AB - Dynamic rotation is a computer-controlled therapy technique utilizing an automated multileaf collimator in which the radiation beam shape changes dynamically as the treatment machine rotates about the patient so that at each instant the beam shape matches the projected shape of the target volume. In simple dynamic rotation, the dose rate remains constant during rotation. For optimized dynamic rotation, the dose rate is varied as a function of gantry angle. Optimum dose rate at each gantry angle is computed by linear programming. Wedges can be included in the optimized dynamic rotation therapy by using additional rotations. Simple and optimized dynamic rotation treatment plans, with and without wedges, for a pancreatic tumor have been compared using optimization cost function values, normal tissue complication probabilities, and positive difference statistic values. For planning purposes, a continuous rotation is approximated by static beams at a number of gantry angles equally spaced about the patient. In theory, the quality of optimized treatment planning solutions should improve as the number of static beams increases. The addition of wedges should further improve dose distributions. For the case studied, no significant improvements were seen for more than 36 beam angles. Open and wedged optimized dynamic rotations were better than simple dynamic rotation, but wedged optimized dynamic rotation showed no definitive improvement over open beam optimized dynamic rotation. PMID- 1518487 TI - The feasibility of interstitial ultrasound hyperthermia. AB - One of the most promising ways to increase the efficacy of brachytherapy is to combine it with hyperthermia. In this paper, the feasibility of using ultrasound transducers as interstitial hyperthermia sources was investigated. The ultrasound output of eight cylindrical transducers (diameter 1 mm and length 25 mm) was studied. It was found that many of these transducers were able to generate between 2 and 3 W of acoustic energy at the frequency of 9.5 MHz. The ultrasound field emitted radially was well collimated and extended the full length of the transducer. In vitro perfused liver and kidney experiments showed that an array of four transducers placed in brachytherapy catheters up to a maximum spacing of 20 mm in a square pattern could induce therapeutic temperatures. Also, the effect of flow rate into the organs and catheter cooling were investigated. These results showed that interstitial ultrasound sources are potentially the most promising way of generating therapeutic temperatures through standard interstitial radiation therapy catheters. PMID- 1518488 TI - Three-dimensional simulations of ferromagnetic implant hyperthermia. AB - A general three-dimensional planning program has been developed for hyperthermia treatments for cancer. In this study, the program is used to analyze the three dimensional temperature distributions generated by interstitial ferromagnetic implants. An empirical power absorption formula developed by Haider for thermally self-regulating nickel-silicon ferromagnetic seeds has been used to calculate the seed power absorption as a function of seed temperature. By properly choosing the seed type (Curie point of seeds), and by using appropriate seed spacing, this heating modality can generate desirable three-dimensional temperature distributions for many different situations over a fairly large range of blood perfusion values. Detailed information regarding the choice of the Curie points of the seeds and the seed spacing for certain blood perfusions is also given as a quantitative guide for treatment planning. PMID- 1518489 TI - A study on the efficacy of digital enhancement of on-line portal images. AB - A novel method for evaluation of observer performance with portal images has been developed, in which the observer is required to identify and localize predefined anatomical landmarks in digital portal images. The method was employed to compare the spatial accuracy and decision time for landmark localization in unenhanced on line portal images and images enhanced digitally by selective adaptive histogram modification. The results indicate that anatomical landmarks were more readily identified in the enhanced images, leading to significantly higher accuracy in landmark localization. PMID- 1518490 TI - [HIV replication is reduced with pentoxifylline administration]. PMID- 1518491 TI - [AIDS in Italy as of 30 September 1991]. PMID- 1518492 TI - [The leukemia-lymphoma syndrome with gastrointestinal involvement in childhood. A case report]. AB - The gastrointestinal tract is an uncommon site of presentation for acute lymphoblastic leukemia in children. We report a child who developed a leukemia lymphoma syndrome with central nervous system and gastrointestinal tract involvement at the diagnosis. The patient received an intensive combination chemotherapy and is currently off-therapy in continuous complete remission 29 months after the diagnosis. PMID- 1518493 TI - [Follicular cysts of the mandible. The diagnostic problems]. AB - The authors describe a case of follicular cyst of the jaw diagnosed in a male infant who was 2 years and 4 months old. The authors discuss recent advances in the classification of this disorder and the difficulties that arise in performing differential diagnosis; some peculiar features of the described case are discussed. PMID- 1518494 TI - [Toxocariasis (visceral larva migrans). A report of a case in an adopted child]. AB - A case of asymptomatic toxocariasis in a Brazilian adopted child with hypereosinophilia is described. The diagnosis is confirmed by measuring specific IgG antibodies anti-Toxocara and, in the light of growing adoptions of children coming from low standard of living extra-European countries, the authors note the importance of investigating also on those parasitosis until today rather infrequent in our country. PMID- 1518495 TI - [The clinical use of dynamic EEG in childhood]. AB - A-EEG is an important recent technologic innovation in EEG recording that facilitates long-term monitoring. The system consists of a miniature cassette tape recorder and a video play-back unit, which permits the taped EEG to be reviewed (Brain Spy CH24, Micromed). Because it is extremely lightweight and portable, the system permits unrestricted activity during recording. On the other hand, this predisposes the recording to more artifacts than are seen in routine recordings. We examined 103 patients, aged 3 months-24 years, between July 1988 and July 1990. Patients were divided into three groups: group 1 included 61 subjects with evidence of epilepsy and clinically definite seizures; group 2 included 29 patients with recurrent episodes that were not clearly epileptic (suspected "pseudo epileptic"); group 3 included 13 subjects with psychiatric disorders. We found that the clinical utility of A-EEG in epileptic children was: 1) obtain better clinical and EEG characterization and circadian distribution of seizures in 17 cases (28%); 2) quantify epileptiform generalized abnormalities and their variations during the sleep in 6 cases (10%); 3) verify the efficacy of specific drug treatment such as Bzd and ACTH in 12 cases (20%). The role of A-EEG in non-epileptic children with pseudoseizures was to establish the epileptic or non epileptic nature of some ictal events by detecting EEG seizure patterns in 11 cases (38%). As to regard the group 3, A-EEG has permitted to study sleep architecture and REM sleep measures, especially in depressed children compared to normal children. We discuss advantages, drawbacks and clinical applications of A EEG in child neurology and psychiatry vs conventional EEG. PMID- 1518496 TI - [The effects of l-dopa administration on the prolactin levels in short-stature subjects]. AB - In this study, on the basis of the inhibiting action of l-dopa administration on prolactin (PRL) secretion, we evaluated in a number of short children the levels of PRL during the provocative stimuli test with l-dopa in order to identify an index able to give reliability to the test and to investigate whether some differences may exist among the subjects showing a different response in growth hormone (GH) secretion to l-dopa. We examined 76 subjects (44 boys and 32 girls) with chronological age from 4.5-15.17 years. The subjects, on the basis of the GH peaks during two provocative stimuli tests [l-dopa and insulin-induced hypoglycemia (IIH)], were subdivided into 3 groups: group 1 (n = 24) with both deficient responses (peak less than 10 ng/ml); group 2 (n = 28) with discordant responses and further subdivided into group 2a (n = 14) with normal responses to IIH and 2b (n = 14) with a normal response to l-dopa; group 3 (n = 24) with both normal responses. PRL levels peaked between times -20' (58 cases) and +20' (2 cases) whereas nadir occurred between +80' (4 cases) and +120 (48 cases) without any significant difference (p = ns) among the groups. PRL levels significantly decreased in all groups, also in those with a deficient response to l-dopa (1 and 2a); furthermore no significant correlation between PRL and GH levels was demonstrated. In conclusion, this study showed the importance of PRL evaluation during l-dopa test in order to give reliability to the test and did not demonstrate any difference in PRL levels among the examined groups of short children. PMID- 1518497 TI - [The use of ofloxacin in cystic fibrosis patients]. AB - The new quinolones represent the latest possibility of specific oral antibiotic treatment of infections caused by gram-negative bacteria. Among the new quinolones, ciprofloxacin and ofloxacin are characterized by strong in vitro activity against most Pseudomonas species strains, favourable kinetic in body fluids, good tolerability and the possibility of oral administration. For these reasons they appear to be ideal antibiotics for long-term home therapy of chronic obstructive pulmonary disease in cystic fibrosis (CF). The efficacy of ciprofloxacin has been recently assessed. In this study, actual effectiveness of ofloxacin in long-term home antibiotic treatment of patients affected by CF was evaluated. The study was a no-blind cross-over study, designed to compare ofloxacin treatment with conventional oral antibiotic therapy. Young adult patients, who needed long-term antibiotic therapy and whom sputum culture were positive for sensitive strains, were randomly assigned to 2 groups. One group received ofloxacin, the other group was given a non-quinolone oral antibiotic, selected according to sputum culture sensitivity. Oral antibiotics were administered for 20 days, then a break of 10 days was allowed during which patients received nebulized aminoglucosides, usually tobramycin. After 3 months, therapies were rotated: the first group received a non-quinolone oral antibiotic and the second group received ofloxacin for another 3 months. The clinical score (according to Huang et al., see table I) and the lung function (FVC, FEV1, pulsed SaO2) were assessed in all the patients at the beginning and at the end of each three months period of oral antibiotic therapy.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1518498 TI - [Pediatric eye emergencies]. PMID- 1518499 TI - Rapid health needs assessment following hurricane Andrew--Florida and Louisiana, 1992. AB - Following the impact phase of Hurricane Andrew in Florida (August 24) and Louisiana (August 26) (Figure 1), the primary objectives of the public health response have been to address the health and medical needs of residents in the storm-damaged areas and to provide data for relief interventions and decision making. This report presents the combined findings from rapid health needs assessment surveys conducted by state health departments with CDC assistance 3-10 days postimpact. PMID- 1518500 TI - Early childhood vaccination in two rural counties--Nebraska, 1991-1992. AB - The national vaccination objectives for the year 2000 include increasing coverage for the recommended primary vaccination series* among children aged less than 2 years to at least 90% and to vaccinate at least 95% of school-aged children (1). Although baseline data for these two goals have been obtained in numerous urban settings (2), similar baseline data from rural populations are limited. To determine the vaccination status of children in rural Nebraska, where 51% (812,000) of Nebraska's residents live, the Nebraska Department of Health, in collaboration with Hastings College, conducted a retrospective study of school aged children in grades kindergarten through six in two rural counties during the 1991-92 school year. This report summarizes the study findings. PMID- 1518501 TI - Update: International Task Force for Disease Eradication, 1992. AB - In 1988, the International Task Force for Disease Eradication (ITFDE) was formed to systematically evaluate the potential for global eradicability* of candidate diseases, identify specific barriers to their eradication that might be surmountable, and promote eradication efforts. In its first four meetings during 1988-1991, the ITFDE examined 15 infectious diseases and determined that four dracunculiasis, poliomyelitis, mumps, and rubella-are good candidates for eradication (1,2). In its fifth meeting in March 1992, the ITFDE evaluated the potential eradicability of six other diseases (Table 1). The criteria used by the ITFDE to evaluate these diseases was provided previously (2). This report summarizes the results of the fifth meeting. PMID- 1518502 TI - Tobacco, alcohol, and other drug use among high school students--United States, 1991. AB - In the United States, use of tobacco, alcohol, and other drugs is associated with the leading causes of morbidity and mortality (e.g., motor-vehicle crashes, homicide, suicide, and cancer [1]), with lower educational achievement, and with school dropout (2-5). This report presents self-reported data about the prevalence of tobacco, alcohol, marijuana, and cocaine use among students in grades 9-12 from two school-based components of the Youth Risk Behavior Surveillance System (6): 1) state and local Youth Risk Behavior Surveys (YRBSs) conducted by departments of education in 23 states and 10 cities during the spring of 1991 and 2) the national YRBS conducted during the same period. PMID- 1518503 TI - Oscillations in glycolysis: multifactorial quantitative analysis in muscle extract. AB - A multifactorial quantitative analysis of oscillations in glycolysis was conducted in the postmicrosomal supernatant of rat muscle homogenates incubated in the presence of yeast hexokinase. Oscillations in adenine nucleotides, D fructose 1,6-bisphosphate, triose phosphates, L-glycerol 3-phosphate, 3HOH generation from D-[5-3H]glucose, NADH and L-lactate production were documented. The occurrence of such oscillations were found to depend mainly on the balance between the consumption of ATP associated with the phosphorylation of D-glucose, as catalyzed by both yeast and muscle hexokinase, and the net production of ATP resulting from the further catabolism of D-fructose 6-phosphate, as initiated by activation of phosphofructokinase. The oscillatory pattern was suppressed in the presence of D-fructose 2,6-bisphosphate. It is proposed that the quantitative information gathered in this study may set the scene for further studies in extracts of cells other than myocytes, e.g. hepatocytes and pancreatic islet cells, in which no oscillation of glycolysis was so far observed. PMID- 1518504 TI - Low density lipoprotein heterogeneity in spontaneously hypercholesterolemic pigs. AB - We previously described a strain of spontaneously hypercholesterolemic pigs carrying an apo-B allele termed Lpb5. Lpb5 pigs are heterogeneous with respect to the severity of their hypercholesterolemia. We have termed Lpb5 pigs with severe hypercholesterolemia Lpb 5.1 pigs, and those with moderate hypercholesterolemia Lpb 5.2, Lpb 5.1 animals have a dramatic increase in buoyant LDL relative to dense LDL, with a buoyant-to-dense LDL ratio of 2.2. In contrast, Lpb 5.2 and control pigs have buoyant-to-dense LDL ratios of 0.7 and 0.5 respectively. This ratio appears to be a stable characteristic of the Lpb 5.1 phenotype because sexually mature boars have a dramatic decrease in total plasma cholesterol concentration with no decrease in their ratio of buoyant-to-dense LDL. We have previously demonstrated a fourteen-fold overproduction of buoyant LDL in the Lpb 5.1 pigs, with very little conversion of dense LDL to buoyant LDL. In the current work, very low density lipoprotein (VLDL) turnover experiments were conducted to determine whether VLDL conversion to buoyant LDL was increased in the Lpb 5.1 pigs. VLDL conversion to buoyant LDL could not account for the increased production of buoyant LDL in Lpb 5.1 pigs. Thus, we cannot account for the increased production of buoyant LDL in the Lpb 5.1 pigs from any measurable plasma lipoprotein source. We have therefore termed this production of buoyant LDL in the Lpb 5.1 pigs direct buoyant LDL production. PMID- 1518505 TI - Analysis of familial hypoalphalipoproteinemia syndromes. AB - Familial hypoalphalipoproteinemias (HA) are a heterogenous group of disorders characterized by various degrees of HDL deficiency. Differential diagnosis involves clinical and biochemical evaluation after intervention designed to correct known secondary causes of low HDL. Two specific HAs are discussed in this report: 1. primary isolated HA (PIHA) is a poorly characterized entity with an apparent autosomal dominant transmission and distinct abnormalities in the structure and function of HDL. 2. Lecithin: cholesterol acyltransferase (LCAT) deficiency syndromes are caused by a number of different genetic defects that lead to at least two distinct clinical presentations i.e. familial LCAT deficiency and fish eye disease. PIHA is an example of a genetic disorder whose diagnosis would greatly be improved by the availability of molecular diagnostic tests. Conversely, the effect of the genetic heterogeneity of LCAT deficiency syndromes on diagnosis is best overcome by utilizing existing biochemical measurement of LCAT activity and the plasma cholesterol esterification rate. PMID- 1518506 TI - Genetic aspects of susceptibility to obesity and related dyslipidemias. AB - Obesity has a multifactorial origin. However, although environmental variables undoubtedly play a role in the development of obesity, it is now clear that genetic variation is also involved in the determination of an individual's susceptibility to body fat accumulation. In addition, it is also widely accepted that obesity is not a single homogeneous phenotype. It is also heterogeneous regarding its causes and metabolic complications. The regional distribution of body fat appears to be an important correlate of the metabolic complications that have been related to obesity. Due to their higher accumulation of abdominal fat, men are generally more at risk for the metabolic complications of obesity than women whereas some obese women, with large gluteal-femoral adipose depots may have a cosmetic problem which may not necessarily require medical intervention. Several studies have been conducted to understand the mechanisms by which abdominal obesity is related to diabetes, hypertension and cardiovascular disease. It appears that the increased risk of abdominal obesity is the result of complex hormonal and metabolic interactions. Studies in genetic epidemiology have shown that both total body fatness and the regional distribution of body fat have a significant genetic component. Standardized intervention studies using an identical twin design have shown that individuals that have the same genetic background tend to show similar changes in body fat and in plasma lipoprotein levels when exposed to standardized caloric excess or energy restriction. Finally, although abdominal obesity is a significant risk factor for cardiovascular disease, not every abdominal obese subject will experience metabolic complications, suggesting that some obese individuals may be more susceptible than others. Variation in several genes relevant to lipid and lipoprotein metabolism may alter the relation of abdominal obesity to dyslipoproteinemias. Abdominal obesity should therefore be considered as a factor that exacerbates an individual's susceptibility to cardiovascular disease. PMID- 1518507 TI - Molecular genetics of human lipoprotein lipase deficiency. AB - Lipoprotein lipase (LPL) hydrolysis the triglyceride core of circulating chylomicrons and very-low-density lipoprotein, and modulates the levels and lipid composition of low and high density lipoproteins. Worldwide, more than 20 mutations in the LPL gene have been identified in patients with familial LPL deficiency. Most of these mutations are clustered in the region encoded by exons 4, 5 and 6 which forms the proposed catalytic domain of LPL. In French Canadians who have the highest reported frequency for LPL deficiency, three common mutations in the LPL gene have been identified which account for approximately 97% of mutant genes in this group. Simple DNA-based tests for the detection of all these mutations have been developed for the screening for carriers of LPL deficiency. This will facilitate further studies of phenotypic expression in heterozygous carriers and assessment of the risk of atherosclerosis in these individuals. PMID- 1518508 TI - Overregularization in language acquisition. AB - Children extend regular grammatical patterns to irregular words, resulting in overregularizations like comed, often after a period of correct performance ("U shaped development"). The errors seem paradigmatic of rule use, hence bear on central issues in the psychology of rules: how creative rule application interacts with memorized exceptions in development, how overgeneral rules are unlearned in the absence of parental feedback, and whether cognitive processes involve explicit rules or parallel distributed processing (connectionist) networks. We remedy the lack of quantitative data on overregularization by analyzing 11,521 irregular past tense utterances in the spontaneous speech of 83 children. Our findings are as follows. (1) Overregularization errors are relatively rare (median 2.5% of irregular past tense forms), suggesting that there is no qualitative defect in children's grammars that must be unlearned. (2) Overregularization occurs at a roughly constant low rate from the 2s into the school-age years, affecting most irregular verbs. (3) Although overregularization errors never predominate, one aspect of their purported U-shaped development was confirmed quantitatively: an extended period of correct performance precedes the first error. (4) Overregularization does not correlate with increases in the number or proportion of regular verbs in parental speech, children's speech, or children's vocabularies. Thus, the traditional account in which memory operates before rules cannot be replaced by a connectionist alternative in which a single network displays rotelike or rulelike behavior in response to changes in input statistics. (5) Overregularizations first appear when children begin to mark regular verbs for tense reliably (i.e., when they stop saying Yesterday I walk). (6) The more often a parent uses an irregular form, the less often the child overregularizes it. (7) Verbs are protected from overregularization by similar sounding irregulars, but they are not attracted to overregularization by similar sounding regulars, suggesting that irregular patterns are stored in an associative memory with connectionist properties, but that regulars are not. We propose a simple explanation. Children, like adults, mark tense using memory (for irregulars) and an affixation rule that can generate a regular past tense form for any verb. Retrieval of an irregular blocks the rule, but children's memory traces are not strong enough to guarantee perfect retrieval. When retrieval fails, the rule is applied, and overregularization results. PMID- 1518509 TI - Active muscle length reduction progressively damages soleus in hindlimb-suspended rabbits. AB - This study describes the morphologic changes in rabbit soleus muscle following hindlimb suspension (HS) for 1 to 4 weeks (group A); or following HS with hindfeet passively dorsiflexed, by means of an elastic band, for 1 to 2 weeks (group B). In the latter, elastic band use allowed phasic contractions of foot extensor muscles against resistance and prevented 35% chronic soleus shortening, which occurred in group A animals. In group A, the soleus revealed progressive muscle atrophy and myofibrillar damage. Myofibrils underwent dissolution, muscle regeneration was ineffective, and adipose tissue developed from about 2-week suspension onward. Conversely, passive dorsiflexion of unloaded hindfeet was essential in maintaining mass and structural muscle integrity in the soleus of group B. It is hereby demonstrated that HS-induced soleus damage in the rabbit is progressive, and can be prevented, avoiding long-term shortening of soleus and its phasic unloaded contractions. Soleus sensitivity to unloading conditions, such as HS, tenotomy, and hypogravity, may depend on the particular physiology of this tonic antigravity muscle, engaged mainly in developing long-lasting isometric contractions in a stretched length. PMID- 1518510 TI - Perioral reflexes in orofacial dyskinesia and spasmodic dysphonia. AB - In order to assess the clinical utility of trigemino-facial reflexes in lower facial muscles, we studied perioral reflexes to mechanical and electrical stimulation in 13 patients with spasmodic dysphonia and orofacial dyskinesia and in 7 healthy subjects. Mechanical stimulation of the upper lip of all patients and electrical stimulation of the infraorbital nerve of patients with orofacial dyskinesia elicited larger perioral reflexes than in controls. In the majority of patients, hyperexcitable perioral reflexes were accompanied by increased gain of the blink reflex. In 4 patients, however, trigemino-facial reflexes were enhanced selectively in either the perioral muscles or orbicularis oculi. Our findings suggest that the quantitative assessment of perioral reflexes may provide information about the excitability of brainstem interneurons in cranial dystonia that is complementary to blink reflex studies. PMID- 1518511 TI - Immunocytochemical localization of the multicatalytic proteinase (proteasome) in crustacean striated muscles. AB - Multicatalytic proteinase (MCP) is thought to play a central role in the processing and turnover of intracellular proteins in eukaryotic cells. Immunocytochemistry was used to determine the intracellular distribution of the MCP in the claw muscles of the land crab, Gecarcinus lateralis, and the claw and abdominal muscles of the American lobster, Homarus americanus. Cryosections were stained with an affinity-purified polyclonal antibody to lobster MCP that cross reacted with the land crab enzyme. Two types of staining were observed: a diffuse cytoplasmic staining, and a dense aggregate staining primarily associated with invaginations of the cell membrane. The cytoplasmic staining appeared reticulated in favorable transverse sections due to a preferential localization of MCP to the intermyofibrillar space. The aggregate staining was associated with neither nuclei nor mitochondria, since stains specific for these organelles (Hoechst stain and nicotinamide adenine dinucleotide diaphorase histochemistry, respectively) did not colocalize with the aggregates. Trypsinlike peptidase activities of isolated microsomal and postmicrosomal fractions indicated that less than 1% of the total MCP was associated with the microsomal fraction. Immunoprecipitation of the same fractions confirmed the presence of MCP in the microsomes as well as in the cytosol. These results suggest that the MCP is primarily associated with cytoplasmic components; the aggregate staining may result from the association of the MCP with cellular membrane systems. PMID- 1518512 TI - Dermatomal somatosensory evoked potentials in the diagnosis of lumbosacral spinal stenosis: comparison with imaging studies. AB - Dermatomal somatosensory evoked potentials (DSEPs) and computerized tomography/magnetic resonance (CT and/or MR) images were retrospectively analyzed to evaluate their relationship in the diagnosis of lumbosacral spinal stenosis (SS). Of 155 patients referred for DSEPs with a clinical suspicion of lumbosacral SS, 58 met the inclusion criteria. DSEP abnormality was defined as: (1) N1 latency absent or greater than 2.5 SD; (2) side-to-side latency difference greater than 2 SD; (3) amplitudes greater than 2 SD below the mean; or (4) amplitude ratio greater than 2 SD. Involvement of two or more DSEP levels by any of the above criteria was labeled multiple root disease (MRD). Involvement of one level was labeled single root disease (SRD). Images were reviewed independently by a neuroradiologist. Results revealed 54 subjects with SS by imaging; 42 had MRD and 8 had SRD by DSEPs. Sensitivity for MRD and SS was 78%, and for MRD plus SRD and SS was 93%. PMID- 1518513 TI - Treatment of hemifacial spasm with botulinum toxin. AB - The effectiveness of botulinum toxin injections in 11 patients with hemifacial spasm was investigated in a prospective placebo-controlled blinded study. The patients were treated with four sets of injections to various facial muscles, selected by clinical evaluation. Three injections were with graded doses of toxin and one was with placebo. The order of injections was random and unknown to the patients. Results were scored both subjectively by patient assessment of symptoms and objectively by blinded review of videotapes made one month after each injection. Subjective improvement occurred after 79% of injections with botulinum toxin, regardless of dose of toxin. Only 1 patient improved after placebo. Objective improvement was seen after 84% of injections with botulinum toxin. No patient showed objective improvement after placebo injection. The most frequent side effect was facial weakness, seen after 97% of injections of botulinum toxin. Facial bruising (20%), diplopia (13%), ptosis (7%), and various other mild side effects were seen less frequently. Botulinum toxin appears to be an effective and safe method of therapy for hemifacial spasm. PMID- 1518514 TI - Short segment incremental studies in the evaluation of ulnar neuropathy at the elbow. AB - Conventional electrodiagnosis may localize an ulnar neuropathy to the general region of the elbow. Separating retroepicondylar compression from compression by the humeroulnar aponeurotic arcade from compression by the deep flexorpronator aponeurosis is more difficult. In 35 patients, we compared localization by conventional inching (stimulating stepwise around the elbow searching for focal conduction block or differential slowing) to localization by a more quantitative short segment incremental stimulation (SSIS) technique assessing latency change over consecutive 1 cm segments. Results of percutaneous studies were compared with findings of intraoperative electroneurography. We conclude that SSIS identifies compression levels more accurately than standard inching, and that SSIS and intraoperative electroneurography correlate highly, but not perfectly. Studies confined to a search for conduction block or differential slowing are limited by the low incidence of conduction block in chronic compression neuropathies. PMID- 1518516 TI - Motor neuropathy with multifocal persistent conduction blocks. PMID- 1518515 TI - Oculopharyngeal muscular dystrophy and mitochondrial abnormalities. PMID- 1518517 TI - Concordant Bell's palsy in monozygotic twins. PMID- 1518518 TI - AAEM case report #25: anterior interosseous nerve syndrome. AB - A case study is reported regarding a 57-year-old woman, chose chief complaint was weakness in her thumb that she had noted while gardening. The patient described difficulty pulling weeds out because of an inability to get a firm grip when using the thumb. Physical examination showed weakness of the flexor pollicis longus and flexor digitorum profundus to the index finger. There was no other weakness and no clinical sensory deficit. Electrodiagnostic studies revealed normal median motor and sensory nerve conduction studies with needle examination abnormalities noted only in the flexor pollicis longus, flexor digitorum profundus, and pronator quadratus. The literature on anterior interosseous nerve syndrome (AINS) is reviewed. It is important to differentiate those with idiopathic AINS as part of a neuralgic amyotrophy picture from those with an anatomic cause such as a fibrous band or anomalous muscle. Electrodiagnostic examination can be useful to help make this distinction. PMID- 1518519 TI - Development of calcitonin-gene-related peptide, chromogranin A, and synaptic vesicle markers in rat motor endplates, studied using immunofluorescence and confocal laser scanning. AB - The presence of calcitonin-gene-related peptide (CGRP) and chromogranin A was investigated in the developing rat (E18-adult) motor system, using immunofluorescence and confocal laser scanning, and compared with synaptic vesicle markers, synaptophysin and synapsin I. In lumbar motor perikarya CGRP-LI and Chr A-LI were present in high intensities in E18 and P1 perikarya in the anterior horn. With increasing age immunoreactivity decreased. Chr A-LI was sparse in the adult. In peroneal endplates, p38-LI and SYN I-LI were present in all stages, including E18. Peptide-LI was very weak or absent in early stages (E18 and P1), but abundant in P8 and P18, especially CGRP-LI, and decreased again in P32 and adult animals. These observations indicate that the peptides have precise functions during certain developmental stages, possibly related to synapse maturation, receptor concentration, and reduction of supernumerary endplates. Both peptides are rapidly transported anterogradely in adult motor axons, and may serve physiological functions also in the adult. PMID- 1518520 TI - SEPs and CNS magnetic stimulation in syringomyelia. AB - Somatosensory evoked potentials (SEPs) and motor evoked potentials (MEPs) to transcranial and spinal stimulation from upper and lower limb muscles were elicited in 13 patients with syringomyelia. Seven had an associated Chiari type I anomaly. Diagnosis was confirmed by MRI. In 5 cases, SEPs and MEPs were performed before and after surgical treatment. Prolonged central motor conduction times or absent motor responses in upper or lower limbs were found in most patients. The greatest number of abnormalities was disclosed by measurement of CMCT followed by SEPs after tibial nerve stimulation. Two of 5 cases undergoing surgery improved clinically and showed reduction in CMCT after surgical treatment. Our study shows that MEPs were useful in the evaluation of neurophysiological status in syringomyelia patients, helping to estimate anterolateral spinal cord function. PMID- 1518521 TI - Binding of malarial circumsporozoite protein to sulfatides [Gal(3-SO4)beta 1-Cer] and cholesterol-3-sulfate and its dependence on disulfide bond formation between cysteines in region II. AB - Region II of the malaria circumsporozoite (CS) protein is highly conserved between the CS proteins of different species of malaria. Amino acid sequences homologous to that of region II are found in thrombospondin, properdin, von Willebrand factor and a few other proteins. We show here that the native CS protein from the rodent parasite Plasmodium berghei, and recombinant Plasmodium vivax and Plasmodium falciparum CS proteins containing region II, but not recombinant proteins lacking region II, specifically bind to sulfatides and cholesterol-3-sulfate. The binding is abolished following reduction and alkylation of the proteins. Region II contains 2 cysteines separated by only 3 amino acids, S(N), V, T, and these are the only cysteines present in our recombinant proteins. Therefore, our findings strongly suggest that the region II cysteines are linked by a disulfide bond forming a small peptide loop. We also present evidence that the recognition of sulfatides, cholesterol-3-sulfate, or other cross-reactive sulfated macromolecules by region II may be required during sporozoite invasion of liver cells. Antibodies to a peptide representing region II react with live sporozoites and with sporozoites fixed with glutaraldehyde, indicating that this region is exposed on the surface of the parasites. Furthermore, we have found that the sulfatide and cholesterol-3-sulfate recognition by the CS proteins, and the invasion of hepatocytes by P. berghei sporozoites, are specifically inhibited by dextran sulfate. PMID- 1518523 TI - Characterisation of a gene for a cysteine protease from Theileria annulata. PMID- 1518522 TI - Distribution and sequence divergence of LRV1 viruses among different Leishmania species. PMID- 1518524 TI - Mapping and partial sequencing of the genes coding for two different cysteine proteinases in pathogenic Entamoeba histolytica. PMID- 1518525 TI - Identification of a Plasmodium falciparum histone 2A gene. PMID- 1518526 TI - The Plasmodium falciparum hypoxanthine-guanine phosphoribosyl transferase gene has a 5' upstream intron. PMID- 1518527 TI - Second form in a segment of the merozoite surface protein 1 gene of Plasmodium vivax among isolates from Rondonia (Brazil). PMID- 1518528 TI - Sequence of the gene for a Trypanosoma cruzi protein antigenic during the chronic phase of human Chagas disease. PMID- 1518529 TI - Pyruvate kinase from Trichomonas vaginalis, an allosteric enzyme stimulated by ribose 5-phosphate and glycerate 3-phosphate. AB - Trichomonas vaginalis pyruvate kinase was purified over 1750 fold to a specific activity greater than 100 mumol min-1 (mg protein)-1. The enzyme is a tetramer of M(r) 266,000, consisting of subunits of M(r) 53,000 and 56,000 in equivalent amounts. Its activity was dependent on the presence of magnesium but was not stimulated by potassium or ammonium. The enzyme exhibited positive cooperativity towards phosphoenolpyruvate and was inhibited by inorganic phosphate, which increased the sigmoidicity of the saturation curve for phosphoenolpyruvate without affecting maximal activity. It was heterotropically stimulated by ribose 5-phosphate and glycerate 3-phosphate, not previously known to act on eukaryotic pyruvate kinases, but was unaffected by known effectors of most pyruvate kinases, including fructose 1,6-bisphosphate and fructose 2,6-bisphosphate. PMID- 1518530 TI - Purification and characterization of a novel sialidase found in procyclic culture forms of Trypanosoma brucei. AB - A membrane-bound sialidase (EC 3.2.1.18) was found in procyclic trypomastigotes of Trypanosoma brucei. The mammalian stage bloodstream form, however, displayed no sialidase activity. This sialidase is an integral surface protein, linked to the membrane via a glycosylphosphatidylinositol anchor. After osmotic lysis and solubilization with Triton CF-54, the enzyme was purified 1900-fold by gel filtration and ion exchange chromatography. Its size, as determined by conventional and high-performance liquid gel chromatography, is 67 kDa. The sialidase is active over a broad pH and temperature range with optima at pH 6.9 and 35 degrees C, respectively. No loss of activity is observed after 4 freeze thaw cycles. T. brucei sialidase activity is inhibited by N-(4-nitrophenyl)oxamic acid and 2-deoxy-2,3-didehydro-N-acetylneuraminic acid, the latter, however, being less effective. N-Acetylneuraminic acid shows no inhibitory effect, whereas a variety of metal ions are potent inhibitors. The sialidase is activated by di- and tricarboxylic acids, but inhibited by chloride. Relative hydrolysis rates of various sialic acid-containing compounds reveal that de-O-acetylated bovine submandibular gland mucin is the preferred substrate and that alpha(2-3)-linkages are hydrolyzed faster than alpha(2-6)-linkages. PMID- 1518531 TI - Succinate-dependent metabolism in Trypanosoma cruzi epimastigotes. AB - Trypanosoma cruzi epimastigotes permeabilized with digitonin (65 micrograms (mg protein)-1) to measure mitochondrial respiration were exposed to different substrates. Although none of the NADH-dependent substrates stimulated respiration, succinate supported not only oxygen consumption but also oxidative phosphorylation (respiratory control ratio of 1.9 +/- 0.3) indicating that the mitochondria were coupled. The rate of NADH-dependent oxygen consumption by membrane fractions (9.4 +/- 0.7 nmol min-1 (mg protein)-1) was reduced by 50% upon addition of catalase indicating that the electrons from NADH oxidation reduced oxygen to H2O2. NADH-dependent H2O2 production (16 +/- 1 nmol min-1 (mg protein)-1) was confirmed using cytochrome c peroxidase. This activity was inhibited by fumarate by 70%, suggesting a competition between fumarate and oxygen for the electrons from NADH, probably at the fumarate reductase level. The respiratory chain inhibitor antimycin blocked both respiration by intact cells and succinate-dependent cytochrome c by isolated membranes. No inhibition by antimycin was observed when NADH replaced succinate as an electron donor, indicating that the electrons from NADH oxidation reduced cytochrome c through a different route. Malonate blocked not only succinate-cytochrome c reductase and fumarate reductase, but also intact cell motility. These results suggest that succinate has a central role in the intermediate metabolism of i. cruzi, as it may be used for respiration or excreted to the extracellular space under anaerobic conditions. In addition, 2 potential sources of H2O2 were tentatively identified as: (a) the enzyme fumarate reductase; and (b) a succinate-dependent site, which may be the semiquinone form of Coenzyme Q9, as in mammalian mitochondria. PMID- 1518532 TI - Molecular characterization of a Dirofilaria immitis cDNA encoding a highly immunoreactive antigen. AB - Dirofilaria immitis, a filarial nematode, is the causative agent of canine and feline heartworm disease. Previous research has demonstrated that immunity to D. immitis can be induced in dogs by repeated chemical abbreviation of infections while the parasite is a fourth-stage larva. Sera obtained from dogs immunized in this manner has been effective in passively transferring larval killing and stunting. These immune sera, by comparison to nonimmune sera from infected cohorts, recognize a number of unique D. immitis antigens, some of which are larval specific. In this study immune dog sera were used to screen a D. immitis larval cDNA expression library. Three overlapping cDNA clones, Di22, Di18 and Di16, were obtained that encode a portion of a large molecule, greater than 150 kDa, that is composed of multiples of a 399-bp repeat. This protein when immunoblotted with antibody against a recombinant expressed Di22 fusion protein is found in larval as well as adult extracts and excretory-secretory products, and is seen as a series of ascending subunits, each approximately 15 kDa larger than the previous one. This antigen is highly immunogenic, as evidenced by the strong reactivity of the recombinant expressed Di22 fusion protein with sera from immune dogs, microfilaremic dogs and infected amicrofilaremic dogs. While the function of this antigen is unknown it has significant sequence similarity with an allergen found in Ascaris. PMID- 1518533 TI - Inter-species variation of schistosome 28-kDa glutathione S-transferases. AB - The 28-kDa glutathione S-transferase from Schistosoma mansoni (Sm28GST) is a candidate vaccine antigen. To evaluate the antigenic and phylogenetic variations between the 28-kDa GSTs from 4 species of schistosome, we have cloned and sequenced the 28-kDa GSTs from Schistosoma haematobium (Sh28GST) and Schistosoma bovis (Sb28GST). Sb28GST and Sh28GST are more similar to each other (97%) than to Sm28GST (90%) and particularly to the 28-kDa GST from Schistosoma japonicum (Sj28GST, 77%). Antisera directed against the major Sm28GST epitopes revealed differences in the recognition of the 28-kDa GSTs from the other schistosome species suggesting that these regions have been subjected to evolutionary pressure. The consequences of such species-specific epitopes on the development of a multi-species anti-schistosome vaccine are discussed. PMID- 1518534 TI - Classification of subgroups of Giardia lamblia based upon ribosomal RNA gene sequence using the polymerase chain reaction. AB - A sensitive and specific polymerase chain reaction-based assay has been developed to detect and analyze polymorphism in the Giardia lamblia 18S ribosomal RNA gene. Efficient amplification required the inclusion of cosolvents (glycerol and dimethyl sulfoxide) in the reaction. Following the optimization of conditions for amplification and subsequent hybridization of amplified product with radiolabeled oligonucleotide probe, a detection limit of less than one organism's worth of DNA was achieved. Thirty-five different G. lamblia strains obtained from various human and animal host types and geographic locations were analyzed by this method. The strains could be divided into 3 groups on the basis of defined nucleotide substitutions within the 183-bp amplified DNA fragment of the 18S ribosomal RNA gene. The groupings based upon the 18S ribosomal RNA gene sequence correlated with groupings previously assigned based upon patterns of surface antigens and restriction enzyme analysis. Analysis of the G. lamblia 18S ribosomal RNA gene sequences present in fecal specimens obtained from giardiasis patients revealed the presence of the different sequence types in these specimens. Some specimens contained more than one sequence type. The identification of subgroups of G. lamblia may facilitate studies of virulence, infectivity, and the epidemiology of giardia infection. PMID- 1518535 TI - Ribosomal DNA sequence comparison of Babesia and Theileria. AB - Previous studies on the taxonomy of Babesia spp. (phylum Apicomplexa) using morphological and life cycle characteristics have resulted in their classification into 3 subgenera, with the genus Theileria being most closely related to them. Using a strategy based on the direct sequence analysis of products derived by asymmetric PCR to determine the nucleotide sequences, we have tested the validity of this classification by sequencing the small subunit ribosomal RNA genes amplified from 2 Babesia species, namely Babesia bovis and Babesia rodhaini, and comparing these with previously published sequences of Theileria annulata and Babesia bigemina using Plasmodium falciparum as an outgroup. The results of this phylogenetic analysis support the recognition of at least 2 genera in Babesia--one to include B. bigemina and B. bovis, the other to include B. rodhaini. PMID- 1518536 TI - A second short repeat sequence detected downstream of rRNA genes in the Entamoeba histolytica rDNA episome. PMID- 1518537 TI - The racial disparity in infant mortality. PMID- 1518538 TI - Occupational exposure to nitrous oxide--not a laughing matter. PMID- 1518539 TI - Plasmapheresis for lupus nephritis. Lupus Plasmapheresis Study Group. PMID- 1518540 TI - Plasmapheresis for lupus nephritis. PMID- 1518541 TI - Plasmapheresis for lupus nephritis. PMID- 1518542 TI - Plasma exchange in polymyositis and dermatomyositis. PMID- 1518543 TI - Management of atrial fibrillation. PMID- 1518544 TI - Management of atrial fibrillation. PMID- 1518545 TI - Hepatitis B in the emergency department. PMID- 1518546 TI - High-dose intravenous immune globulin and acute renal failure. PMID- 1518547 TI - Mortality after vasectomy. PMID- 1518549 TI - The heart in hypertension. PMID- 1518548 TI - Clinical determinants of the racial disparity in very low birth weight. AB - BACKGROUND: Although the risk of very low birth weight (less than 1500 g) is more than twice as high among blacks as among whites in the United States, the clinical conditions associated with this disparity remain poorly explored. METHODS AND RESULTS: We reviewed the medical records of over 98 percent of all infants weighing 500 to 1499 g who were born in Boston during the period 1980 through 1985 (687 infants), in St. Louis in 1985 and 1986 (397 infants), and in two health districts in Mississippi in 1984 and 1985 (215 infants). The medical records of the infants' mothers were also reviewed. These data were linked to birth-certificate files. During the study periods, there were 49,196 live births in Boston, 16,232 in St. Louis, and 16,332 in the Mississippi districts. The relative risk of very low birth weight among black infants as compared with white infants ranged from 2.3 to 3.2 in the three areas. The higher proportion of black infants with very low birth weights was related to an elevated risk in their mothers of major conditions associated with very low birth weight, primarily chorioamnionitis or premature rupture of the amniotic membrane (associated with 38.0 percent of the excess proportion of black infants with very low birth weights [95 percent confidence interval, 31.3 to 45.4 percent]); idiopathic preterm labor (20.9 percent of the excess [95 percent confidence interval, 16.0 to 26.4 percent]); hypertensive disorders (12.3 percent [95 percent confidence interval, 8.6 to 16.6]); and hemorrhage (9.8 percent [95 percent confidence interval, 5.5 to 13.5]). CONCLUSIONS: The higher proportion of black infants with very low birth weights is associated with a greater frequency of all major maternal conditions precipitating delivery among black women. Reductions in the disparity in birth weight between blacks and whites are not likely to result from any single clinical intervention but, rather, from comprehensive preventive strategies. PMID- 1518550 TI - Mechanism of dialysis-induced hypotension. AB - Dialysis-induced hypotension, the sharp decrease in blood pressure occurring during hemodialysis, remains one of the most difficult problems associated with hemodialysis even today. However, there is yet no established theory to explain the mechanism triggering dialysis-induced hypotension. This review attempts to offer a consistent and cohesive source of information on the hemodynamics during dialysis-induced hypotension, and then analyzes etiologic factors in such hypotension reported by various investigators. Finally, three hypotheses concerning the mechanism of dialysis-induced hypotension including our own are introduced. PMID- 1518551 TI - Regulatory role of heat shock protein-specific T cells in host defense. AB - During infection with L.monocytogenes, a facultative intracellular bacteria, TcR gamma/delta T cells specific for 65 kd hsp precede TcR alpha/beta T cells specific for the listerial antigens in appearance. The gamma/delta T cells provide a first line of defense against the infection by recognizing exogenous and endogenous 65 kd hsp on infected cells and producing cytokines such as gamma IFN. The hsp-specific T cells respond quickly to antigenically diverse pathogens before antigen-specific T cells expand clonally, and they play a role in covering the gap between the phagocytic system and highly evolved immune response. 65 kd hsp-specific T cells play important roles not only in host defense mechanism against infection with various pathogens but also in induction of auto-immune disease. Both 65 kd hsp-specific gamma delta T cells and 65 kd hsp-specific alpha beta T cells abrogate the unresponsiveness of the self-reactive alpha beta T cells and/or B cells by producing IL-2 and contribute to induction of autoimmune disease. PMID- 1518552 TI - Progression of avascular necrosis of femoral head and choice of treatment. AB - Observations of the disease course mainly by X-ray were made in 52 patients (85 joints) with avascular necrosis of the femoral head to determine the prognosis and to decide on treatment. The progression of the necrotic area is related to the activity of the original disease, to the size of the necrotic area in the early stages of the disease, and to whether or not the patient received steroid treatment. On the basis of the size and location of the necrotic area, the disease process is divided into four stages, I to IV. The affected heads are also classified into six types according to their site and extent, the degree of flatness of their weightbearing surface, and the presence of cystic lesion. Preventive treatment and conservative observation or transtrochanteric anterior rotational osteotomy and vascularized pedicle bone graft are applicable to cases in Stages I and II. Total hip joint arthroplasties and salvage procedures are performed in Stages III and IV. The usefulness of 99mTc bone scintigraphy was unexpectedly disappointing for diagnosis of the stages of the disease. However, MRI was sensitive for the diagnosis in the early stages of the disease. PMID- 1518553 TI - Isolation and some biochemical properties of porcine pancreas mitochondria. AB - Morphologically and functionally intact mitochondria were isolated from the porcine pancreas using a conventional, differential centrifugation method. The homogenate of the porcine pancreas made in a medium containing 0.25 M sucrose, 10 mM Tris-Cl, pH 7.4, 0.5% bovine serum albumin and 1 mM EDTA, in the presence or in the absence of dibucaine and trypsin inhibitor, was centrifuged for 10 min at 700xg. The supernatant was centrifuged for 10 min at 7000xg, and the pellet was washed three times. Trypsin activity of mitochondria isolated in the absence of dibucaine and trypsin inhibitor was as low as that of mitochondria isolated in the presence of dibucaine and trypsin inhibitor, and a major part of the activity remained inactivated. Phospholipase A2 activity of the former mitochondria was as low as that of the latter, and remained unchanged up to 8-10 hr at 4 degrees C. The presence of bovine serum albumin and EDTA in the respiration medium was absolutely required to obtain good respiratory controls of those mitochondria. These data suggest that well-coupled mitochondria can be obtained from the pancreas by a conventional isolation procedure without activating the major part of trypsin. PMID- 1518554 TI - Esophageal stenting with a self-expandable metallic device: a preliminary study. AB - This study was designed to investigate the potential of the Gianturco-Rosch Z stent in the alimentary canal, using the rabbit esophagus as the animal model. Single stents were implanted in four animals, which were followed up for predetermined periods, lasting from 48 hours to 6 weeks. All the stents remained in place. A florid tissue reaction was noticed, initially manifesting primarily as submucosal cellular infiltration, and mucosal erosion. Over the ensuing six weeks, the acute changes gave way to mucosal regeneration, and the appearance of granulation tissue in the submucosa. The stented segments remained patent, and feeding difficulties were limited to the immediate post-procedure period. These preliminary results suggest that peristaltic activity is no contraindication to the use of Z stents, though measures to limit the tissue response need to be identified. PMID- 1518556 TI - Remarkable hepatic vein-to-vein anastomoses in giant cavernous hemangioma of the liver: a case report. AB - Intrahepatic venous collaterals develop in Budd-Chiari syndrome, hepatomas, and other tumors if the hepatic veins are obstructed. In portal hypertension hepatic vein-to-vein anastomoses develop without obstruction of the hepatic veins. In a 53-year-old woman with giant cavernous hemangioma of the liver, hepatic venography demonstrated remarkable hepatic vein-to-vein anastomoses in the periphery of the hepatic veins without venous obstruction, accompanied with low wedged hepatic vein pressure. The hemodynamic change of the liver may cause this abnormality because of the large blood space of the hemangioma. Pathological examination of the resected liver apart from the tumor confirmed numerous deformations and dilatations of the central veins not found in the normal liver, in the area of hepatic vein-to-vein anastomoses shown by venography. Clinically, atypical hepatic resection is possible by maintaining a drainage vein to preserve as much of the normal liver as possible. Hepatic venography, as well as hepatic angiography, gives important information about the liver. PMID- 1518555 TI - The effect of hypophysectomy on proluminal movement of 3H-androgens across the epididymal epithelium in the rat. AB - The effect of hypophysectomy on transepithelial movement of 3H-androgen in the rat epididymis was examined by using in vivo microperifusion of 3H-testosterone followed by in vivo micropuncture to obtain peritubular and intraluminal fluids. Experiments were performed on animals without hypophysectomy or on animals 5-6 days after hypophysectomy and 9-10 days after hypophysectomy. Tubules were perifused with Minimum Essential Medium containing 3H-testosterone. 14C polyethyleneglycol was included in the perifusion fluid as a marker for contamination of the intraluminal fluid by peritubular fluid. Radioactivity of isotopes in the interstitial and intraluminal fluid was determined at 1 and 2 hours after perifusion and the percentage of peritubular isotopes appearing in the intraluminal fluid was determined. A sperm concentration microassay was performed on micropuncture samples from the epididymal tubules to assess testicular contribution to the lumen content. Proluminal movement of 3H-androgen and intratubular sperm concentrations in the caput epididymal tubules of rats 9 10 days after hypophysectomy were significantly decreased. Proluminal movement of 3H-androgen and intratubular sperm concentrations in the cauda epididymal tubules of rats 9-10 days after hypophysectomy were significantly increased. These results suggest that proluminal androgen movement is controlled by the presence of some testicular product in the epididymal lumen. PMID- 1518557 TI - Movement study following anterior cervical decompression without fusion. AB - Movement studies of the neck have shown that certain patients with cervical spondylotic myelopathy (CSM) demonstrate instability in the vertebral joint immediately above the posterior osteophytic bar. While Cloward's anterior cervical decompression with fusion eliminates the cord or root compressive element, it adds to the hypermobility of the adjoining vertebral segment. In an attempt to reduce the hypermobility or subluxation, anterior cervical decompression without fusion was carried out on a selected group of twenty-three patients with spondylotic cervical myelopathy in whom the cord compression was mainly at a single level. Follow-up cineradiographic studies of these cases demonstrated the continued preservation of the range of movement of the adjoining vertebral segments and in 30%, a return of normal functional mobility to the affected cervical intervertebral joint. The findings and results of anterior cervical decompression surgery to a single level are reported. PMID- 1518558 TI - Current bibliographies of neuropeptides prepared by the University of Sheffield Biomedical Information Service. PMID- 1518559 TI - Inhibitory effects of okadaic acid on thyrotropin and prolactin secretion from rat anterior pituitaries. AB - The present study was undertaken to elucidate the effects of okadaic acid, a potent inhibitor of protein phosphatases, on thyrotropin (TSH) and prolactin (PRL) secretion, and on the hydrolysis of inositol phospholipids in rat anterior pituitaries. Preincubation of anterior pituitaries with okadaic acid caused a dose dependent decrease in TRH- and K(+)-induced TSH secretion, whereas basal secretion of TSH was not affected by pretreatment with okadaic acid. In contrast, okadaic acid resulted in a marked inhibition in both basal, and TRH- and K(+) stimulated PRL release from anterior pituitaries. In addition, pretreatment with okadaic acid caused a slight, but significant decrease in the formation of [3H]inositol phosphate ([3H]IP) in rat anterior pituitaries. The present study suggests that okadaic acid blocks the release of TSH and PRL by inhibiting Ca2+ influx and that inhibitory effects of okadaic acid on PRL release are, at least in part, due to the inhibition of inositol phospholipid hydrolysis. PMID- 1518560 TI - The effect of C-terminus and N-terminus iodination on avian pancreatic polypeptide (APP) binding to its chicken brain receptor. AB - In previous studies, membranes from chicken gastrointestinal tissues failed to bind appreciable levels of 125I-APP labeled at the C-terminus. In order to address the suggestion that this was due to steric hindrance of the critical C terminus, N-terminally labeled 125I-APP was utilized in in vitro membrane binding assays. Membranes from chicken cerebellum and spleen specifically bound N terminally iodinated APP, while those from gastrointestinal tissues including pancreas, mucosal and muscle layers of duodenum and proventriculus did not. Cerebral cortex membranes also failed to specifically bind Bolton-Hunter labeled 125I-APP. Liver membranes, which previously were shown to bind C-terminally iodinated APP with low affinity, also did not specifically bind N-terminally labeled preparations. It is concluded that the inability of membranes from gastrointestinal tissues and brain regions other than cerebellum to bind 125I-APP is not an artifact of location of iodine placement on the molecule and that both the N- and C-termini may be important for receptor binding. It is also concluded that liver APP binding sites may be structurally distinct from those in the cerebellum, and that gastrointestinal tissues may not be direct targets for APP action. PMID- 1518561 TI - Sites of synthesis of chromogranins A and B in the human brain. AB - The sites of synthesis of the chromogranins A and B, and their potential processed peptides, were examined by quantitating the levels of chromogranin A and B mRNA in various regions of the human brain by Northern blot analysis. Chromogranin A and B mRNA expression in the brain is region-specific and confined to grey matter. In situ hybridization histochemistry detected chromogranin A and B mRNA in pyramidal neurons of human cerebral cortex. Cell-specific expression in subpopulations of cerebrocortical neurons suggest that chromogranin A and B gene products may play a role in central neuronal function. PMID- 1518562 TI - Glycosylation variants of endopeptidase-24.11 ('enkephalinase'). AB - Anion exchange chromatography resolves two charge variants of rat kidney endopeptidase-24.11 (designated NEP 1 and NEP 2); each was purified to homogeneity using immunoaffinity chromatography. In addition to charge differences the subunit molecular weights of NEP 1 and NEP 2 differ and are 89 and 96 kDa, respectively. Isoelectric focusing resolved 8-10 pl species in the pH range of 5.95-6.20 for NEP 1 and 5.46-6.06 for NEP 2. Removal of sialic acid residues converted the multiple pl species to one form with a pl of 6.32 for NEP 2, and two forms with pls of 6.27 and 6.32 for NEP 1. Endoglycosidase H or F, capable of removing high-mannose and biantennary branched N-linked oligosaccharides, produced a 2-3 kDa decrease in the molecular weight of both NEP 1 and NEP 2. Peptide-N-glycosidase F, capable of removing all classes of N-linked oligosaccharides, produced 8 and 11 kDa decreases in NEP 1 and NEP 2, respectively. Removal of all N-linked and O-linked oligosaccharides with trifluoromethanesulfonic acid resulted in 10 and 15 kDa decreases in NEP 1 and NEP 2, respectively. Tryptic epitope maps demonstrated that NEP 2 was cleaved at a slower rate than NEP 1. These analyses demonstrate that rat kidney NEP exhibits sialic acid microheterogeneity resulting in two distinct change variants. The data also indicate that NEP 2 contains more N- and O-linked carbohydrate mass than NEP 1 and may contain a larger polypeptide backbone giving rise to molecular weight differences between these enzyme forms. PMID- 1518563 TI - Cognitive representations of the political system in adolescents: the continuum from pre-novice to expert. PMID- 1518564 TI - Lay social theory: the relation between political, social, and moral understanding. PMID- 1518565 TI - Political tolerance: how adolescents deal with dissenting groups. PMID- 1518566 TI - The personal and the political in reasoning and action. PMID- 1518567 TI - Childhood origins of beliefs about institutional authority. PMID- 1518568 TI - Young adults' understanding of political issues: a social-ecological analysis. PMID- 1518569 TI - Decision making. Stability of clinical decisions. AB - Clinical decisions of 101 medical-surgical nurses were examined for stability. Results indicate that slightly more than 50% of the subjects made stable clinical decisions or decisions not likely to be reversed with minor changes in the clinical data. The findings also reveal that stability was related to hospital setting and country in which the nurses received their education. The authors provide possible explanations for these observations, and recommendations for nursing education and practice. PMID- 1518570 TI - An approach to publishing an edited book. AB - This article outlines the steps taken by the authors to publish a co-edited nursing research book to assist nurses interested in editing a book or writing a book chapter. The authors' experiences are used to help illustrate the preparation and editing of manuscripts. Collaboration among co-editors, chapter authors (contributors), and the staff of the publishing company is vital when publishing an edited book. PMID- 1518571 TI - Client satisfaction with student care in a nurse-managed center. AB - Nursing faculty across the country are developing nurse-managed centers to provide students with community health experiences. Although students deliver much of the care provided within nursing centers, the literature offers little data on the quality of student-rendered care. This study evaluated client satisfaction with care received from student nurses. Results have direct implications for faculty supervising students in community health nursing agencies. PMID- 1518572 TI - The importance of writing style. PMID- 1518573 TI - The optimal environment for socialization of the nurse-scientist. AB - Tangible elements or factors that contribute to the successful socialization of student scholars seeking the PhD degree in nursing are generally well known. Included among these are the university itself-its faculty, its resources, such as laboratories and libraries, and its research productivity. Less well known are some intangibles in the learning environment that make the difference between an acceptable learning environment and an optimal one, such as, the frequency and quality of informal interaction between faculty and students. The author identifies several characteristics of the pre-doctoral learning environment for nurse PhD students that faculty and administrators should seek to provide if they wish to support truly successful socialization of the scholar/scientist. PMID- 1518574 TI - Strategies to enhance problem solving. AB - The ability to make high-level decisions based on a strong knowledge base and effective problem-solving strategies is an expected behavior of the professional nurse. The author discusses current knowledge of problem-solving components and teaching strategies as well as promising new computer strategies that are applicable to nursing education and practice. PMID- 1518575 TI - IV simulators from recycled materials. PMID- 1518576 TI - Experiential learning: a "real-world" introduction for baccalaureate nursing students. PMID- 1518577 TI - A classroom activity to introduce cultural diversity. AB - The authors describe an activity designed to introduce cultural diversity to an undergraduate developmental psychology course in a nursing baccalaureate program. The students' responses to the activity served as the basis for a discussion of stereotypes and their effects on culturally diverse populations. The student responses are described and the importance of introducing cultural diversity into mainstream education is discussed. PMID- 1518578 TI - Helping students cope. PMID- 1518580 TI - The ABCs of maintaining clinical competence. PMID- 1518579 TI - Linking community needs with student research experiences. AB - The authors describe the activities of the Action Research program, designed to link academic projects and requirements for student research activities with the information needs of community service agencies. While interdisciplinary in focus, this program has been especially helpful in allowing community health nursing students to gain practical experience with real-life research questions and processes. An added benefit is to instill in the student an attitude of service while expanding their orientation to the community and the everyday needs of its agencies. PMID- 1518581 TI - Educating for sensitivity to cultural diversity. PMID- 1518582 TI - The family log: a tool to enhance parent-child nursing. PMID- 1518583 TI - Developing case studies. AB - The case method stimulates critical thinking through problem analysis of real or hypothetical cases. Developing clear, concise, fact-filling cases that promote problem solving in the classroom is not easy. The author presents a systematic, seven-step process for case construction. PMID- 1518584 TI - The challenge of controlling tuberculosis in New York City. PMID- 1518585 TI - Tuberculosis in New York: rapid rise of a preventable disease. PMID- 1518586 TI - Bronchitis mimicking opportunistic lung infection in patients with human immunodeficiency virus infection/AIDS. AB - Purulent bronchitis was identified in 19 of 422 patients undergoing fiberoptic bronchoscopy during a 32-month period because of suspicion of an opportunistic lung infection complicating acquired immunodeficiency syndrome or human immunodeficiency virus infection. Five patients had Pneumocystis carinii pneumonia, but other opportunistic lung infections were excluded in the remaining 14 patients. Characteristics of these 14 patients included fever (greater than 38.3 degrees C), cough, and dyspnea in 14 of 14 patients; purulence of expectorated sputum (11/14); and widened alveolar-arterial oxygen gradient (13/14). Rapid (2 +/- 1.4 days) clinical response (defervescence and resolution of pulmonary symptoms) occurred with antibiotic therapy in 10 of 14 patients. In three patients, there was no improvement, and adult respiratory distress syndrome developed. Bacterial isolates from bronchoalveolar lavage included Streptococcus viridans (n = 12), Haemophilus influenzae (n = 7), Staphylococcus aureus (n = 3). Roentgenographic features of bronchiectasis were present in seven patients. Differential cell counts revealed greater than 50% neutrophils in the bronchial washings of all patients with purulent bronchitis. Neutrophil percentages in bronchoalveolar lavage were as follows: patient with purulent bronchitis without P carinii pneumonia (n = 14), 54.53% +/- 29.18%; patients with purulent bronchitis and concomitant P carinii pneumonia (n = 5), 62% +/- 31.9%. In a control group of 17 patients with P carinii pneumonia who did not have purulent bronchitis, the neutrophil percentage was 6.8% +/- 6.17% (p = less than 0.00001, t-test). Purulent bronchitis appears to be a distinct, treatable entity in patients with HIV infection and may accompany bacterial pneumonia, bronchiectasis, and P carinii pneumonia. PMID- 1518587 TI - Munchausen syndrome. PMID- 1518588 TI - Memories of an internship in 1943. PMID- 1518590 TI - Cystic benign lymphoepithelial lesion of the parotid gland in an HIV-infected patient. PMID- 1518589 TI - Purpura fulminans, metastatic endophthalmitis, and thrombotic thrombocytopenic purpura in an HIV-infected patient. PMID- 1518591 TI - Ten-year survival in multiple myeloma: report of two cases and review of the literature. PMID- 1518592 TI - Trauma-related presentation of non-Hodgkin's lymphoma. PMID- 1518593 TI - Chemotherapy for hepatic angiosarcoma. PMID- 1518594 TI - New hospice benefit available for nursing home residents. PMID- 1518595 TI - The role of third party payors in medical care. PMID- 1518596 TI - Nurse sabbatical: reflections on professionalism. PMID- 1518597 TI - Understanding age-related values in the work force. PMID- 1518598 TI - Culture of excellence in home care... PMID- 1518599 TI - Why not let the name evolve? PMID- 1518600 TI - More on healing the spirit. PMID- 1518601 TI - Traveling poster project. PMID- 1518602 TI - The D.A.R.E. bedside emergency method. Data, action, response and evaluation. PMID- 1518603 TI - Recruiting for outlying nursing stations. PMID- 1518604 TI - Competency-based orientation: a solution. PMID- 1518605 TI - Non-nursing tasks: do they make 'cents'? PMID- 1518606 TI - Understanding the Safe Medical Devices Act of 1990. PMID- 1518607 TI - Medic alert! PMID- 1518608 TI - Maintaining respect. PMID- 1518609 TI - Patient Self-Determination Act. PMID- 1518610 TI - Mentorship in nursing management... PMID- 1518611 TI - Help for the shortage of nursing faculty. PMID- 1518612 TI - Hospital policy: proposing and disposing. PMID- 1518613 TI - Learning from software development failures. PMID- 1518614 TI - Medicare home health cost ceilings increased substantially. PMID- 1518615 TI - The role and functions of the hospital nurse manager. American Organization of Nurse Executives. PMID- 1518616 TI - Healthcare polarities: quality and cost. PMID- 1518617 TI - Nursing assessments: patient severity of illness. PMID- 1518618 TI - Work sampling nursing units. PMID- 1518619 TI - Work sampling in ambulatory care nursing. PMID- 1518620 TI - Using Havelock's model to plan unit-based change. PMID- 1518621 TI - Project management: new approaches. PMID- 1518623 TI - Mirror, mirror on the wall. PMID- 1518622 TI - A manager's dilemma: paranoid thinking. PMID- 1518624 TI - A decision tree approach to sensible solutions. PMID- 1518625 TI - Marketing messages: preferences, perceptions and performance. PMID- 1518626 TI - Report hits hospital quality standards. PMID- 1518627 TI - Industrial athletes. PMID- 1518628 TI - AIHA evaluates how respirator protection is measured in workplace. PMID- 1518629 TI - Oh Henry. Interview by Blake Smith. PMID- 1518630 TI - Personal Protective equipment: PPE. PMID- 1518631 TI - Process safety. PMID- 1518632 TI - The heat is on. PMID- 1518633 TI - A retrospective study of patients with cluster headaches. AB - Referred pain in the midface and teeth is a common clinical feature of the cluster headache and cluster headache-like disorders. It is not unusual therefore for patients with cluster headaches to go to the dentist. In this report, 33 cases of cluster headache, which met the International Headache Society classification criteria, and which were seen by us during a 2-year period, are reviewed. Fourteen (42%) of 33 patients who were seen by dental practitioners and who received some form of ineffective dental or pharmacologic treatment are described here. Since almost 50% of the cluster headache patients described here received inappropriate dental treatment, it is hoped that this review and retrospective assessment will make the dental practitioner aware of this disorder and provide a broader perspective in the treatment of pain in the orofacial region. Clinical presentation, pathogenesis, and treatment of cluster headaches are discussed. PMID- 1518634 TI - Lateral canthotomy transconjunctival approach to the orbit. AB - Multiple surgical approaches to the orbits with the use of the eyelids have been used. The orbital rim incision fell into disfavor because of esthetic considerations. A subciliary approach supplemented by the lateral brow incision is currently the most popular method of approach to the orbital rim. It provides adequate access to the orbit, but it is not without inherent complications, such as unfavorable scarring, ectropion, and entropion. This article describes an alternate approach to the orbit by means of a transconjunctival incision with lateral canthotomy. PMID- 1518635 TI - Rehabilitation of the temporomandibular joint after arthroscopic surgery. AB - Arthroscopy of the temporomandibular joint (TMJ) is a new, relatively noninvasive surgical procedure for treating patients with TMJ dysfunctions beyond management by nonsurgical means. Ninety-two patients who underwent diagnostic and operative TMJ arthroscopy completed a staged physical therapy regimen, which resulted in functional mobility and mandibular use with little or no pain at 24-month follow up. This report introduces TMJ arthroscopic diagnostic and surgical procedures and their respective rehabilitative protocols currently used to provide beneficial outcomes in postoperative treatment. PMID- 1518636 TI - Pulpal anesthesia dependent on epinephrine dose in 2% lidocaine. A randomized controlled double-blind crossover study. AB - We studied the discrepancy in the results published on the dependence of the duration of pulpal nerve anesthesia on the concentration of epinephrine in 2% lidocaine. The increase in pain threshold of the pulpal nerve was measured before and after injection of lidocaine alone and lidocaine with epinephrine concentrations of 1:200,000, 1:100,000, or 1:50,000 into the mucobuccal aspect adjacent to the apex of the maxillary right incisor. The study was done in a random manner with a double-blind crossover design. The pulpal nerve was stimulated with negative rectangular electrical pulses of up to -167 V with 100 Hz and a pulse width of 0.6 msec. The results show a relationship between the 1:200,000 and 1:100,000 epinephrine concentrations and the success and duration of anesthesia. The onset of anesthesia was independent of the catecholamine content of the solution. PMID- 1518637 TI - Replacement of freeze-dried allogeneic cartilage chin graft with host bone. A case report. AB - Facial contour and augmentation procedures are frequently performed by oral and maxillofacial surgeons either as a primary surgery or in conjunction with corrective jaw surgery. The success of these procedures depends on the stability of the material used. This case demonstrates the stability and eventual osseous replacement of allogeneic freeze-dried cartilage as an augmentation material. PMID- 1518638 TI - Two natal maxillary molars. Report of a case. AB - A 20-day-old black male infant with two rare posterior natal teeth was referred for examination and care. Oral radiographs suggested that the teeth were the right and left maxillary primary molars. The hypermobile teeth and associated suspicious soft tissue masses were removed. Histologic examination revealed irregular tooth structures and infiltrate consistent with inflamed dental follicles. PMID- 1518639 TI - Trismus caused by a retained foreign body in an adult. PMID- 1518640 TI - Ameloblastic fibroma and impacted mandibular first molar. A case report. PMID- 1518641 TI - Postscaling bacteremia in HIV-associated gingivitis and periodontitis. AB - Aseptic venipuncture was used to obtain samples of blood from 22 patients seropositive for human immunodeficiency virus (HIV) with gingivitis (HIV-G) and 19 HIV-seropositive patients with periodontitis (HIV-P), 15 and 30 minutes after the initiation of routine dental scaling and root planing. The presence of colony forming units in 1.2 ml aliquots of blood collected with the Isostate system (DuPont Isostat System, Doraville, Ga.) was assayed on trypticase soy blood agar. Six of the samples from HIV-G subjects were positive for colony forming units 15 minutes after scaling but not at 30 minutes. Similar evidence of bacteremia was found in seven of the HIV-P patients 15 minutes after scaling was initiated in this group, with no microbial growth detectable in samples obtained at 30 minutes. In two HIV-G and three HIV-P patients with demonstrable bacteremias a postoperative fever developed. For both HIV-G and HIV-P groups no significant difference was found between the absolute CD4 T-cell counts of nonbacteremic versus bacteremic patients (p greater than 0.05). These observations suggest that special provisions for antibiotic prophylaxis in this patient group may be unnecessary. PMID- 1518642 TI - Retrospective findings of the clinical benefits of podophyllum resin 25% sol on hairy leukoplakia. Clinical results in nine patients. AB - Hairy leukoplakia was first described as an oral marker of human immunodeficiency virus infection in 1984. The clinical significance of this lesion in an otherwise healthy, high-risk symptom-free person is that it can be an early manifestation of human immunodeficiency virus infection. Because of its benign nature and the lack of clinical evidence that treatment of the lesion improves the prognosis of human immunodeficiency virus-infected patients, systemic therapy with antiviral drugs does not seem warranted at this time. Topical retinoids (Retin-A sol) and systemic antivirals such as acyclovir have been previously tried; however, lesions tend to recur a few days after treatment is discontinued. Nine patients with oral hairy leukoplakia seen at the Oral Medicine Clinic, University of California San Francisco were offered treatment with podophyllum resin 25% sol. All patients had a complete remission of their condition within 1 week (5 patients) or after the second application a week later (4 patients). Side effects were transient and reversible. These remissions of oral hairy leukoplakia lasted from 2 to 28 weeks, which suggests that podophyllum may be a relatively safe and cost-effective treatment of this otherwise symptom-free lesion. PMID- 1518643 TI - Candida species and Candida albicans morphotypes in erythematous candidiasis. AB - A group of full-denture-wearing patients with erythematous candidiasis was matched by age and sex with a group of healthy, full-denture-wearing persons who served as controls. In the group with erythematous candidiasis, clinical symptoms and signs of the disease were recorded. Denture hygiene and tobacco use were noted in both groups. Epithelial smears and imprint cultures were obtained from both groups from specified sites. Cultures were grown and subjected to species identification and C. albicans strain differentiation by a morphotyping technique. Denture-wearing subjects who smoked tobacco had a significantly greater incidence of erythematous candidiasis than the controls. Five species of Candida were isolated from both groups, with C. albicans as the dominant species. Twenty different morphotypes of C. albicans as well as strains involved in erythematous candidiasis were also isolated from the oral cavities of healthy, full-denture-wearing control subjects. PMID- 1518644 TI - An unusual case of hemifacial atrophy. AB - A case of hemifacial atrophy in a 10-year-old boy is described. The presentation in this patient is unusual because the lesion is extremely localized, and the abnormalities of teeth in the affected region are more severe than previously recorded. Alternative diagnoses are considered, and the results of a computed tomographic scan with three-dimensional reformatting are presented. PMID- 1518645 TI - Chronic ulcerative stomatitis associated with stratified epithelial specific antinuclear antibodies. A case report of a newly described disease entity. AB - A case of erosive oral lesions associated with an unusual direct and indirect immunofluorescent pattern is presented. Rather than a submucosal band or intramucosal intercellular deposition, the pattern is that of an antinuclear antibody that reacts only with stratified epithelium. The clinical similarity of this case to erosive lichen planus is discussed. The usefulness of direct and indirect immunofluorescence techniques in the diagnosis of erosive oral lesions is stressed. PMID- 1518646 TI - Production of microliths and sialadenitis in rats by a short combined course of isoprenaline and calcium gluconate. AB - The relationship between microliths and sialadenitis in man is unclear, so an attempt was made to investigate it experimentally in rats with the use of isoprenaline and calcium gluconate either alone or combined. The acini of the submandibular and parotid glands of rats that were given isoprenaline were enlarged, and degenerate acinar cells were seen, with extravasated secretions in the submandibular gland. Similar changes were seen in the submandibular and parotid glands of rats that were given isoprenaline combined with calcium gluconate; in addition, ductal microliths with regions of atrophic sialadenitis were observed. The results suggest that there is temporary obstruction to the salivary flow after isoprenaline is injected, and in the rats that were also given calcium gluconate some of the stagnant saliva calcified to form microliths, which produced a lasting obstruction and obstructive sialadenitis. This supports the possibility that microliths, which are present in normal salivary glands of man, are a primary etiologic factor in sialadenitis. PMID- 1518647 TI - Low-grade papillary adenocarcinoma of minor salivary glands. Case report and literature review. AB - Low-grade papillary adenocarcinoma of minor salivary glands is rare and tends to occur in the palate. This tumor has distinct but rather deceptive histomorphologic features, which may cause erroneous diagnosis. An extensive English-language literature review revealed reports of 22 well-documented low grade papillary adenocarcinomas. Six of these tumors (27%) recurred locally between 12 months and 19 years after initial treatment. Low-grade papillary adenocarcinoma appears to have more aggressive biologic behavior compared with other low-grade adenocarcinomas in this region. Four of the reported cases (17%) had cervical lymph node metastases at the time of presentation. We report an additional case and discuss the literature. PMID- 1518648 TI - Intraoral infantile hemangiopericytoma: literature review and addition of a case. AB - A rapidly growing neoplasm in the buccal mucosa of a 4-month-old baby was excised. By light and electron microscopy the neoplasm had features that were similar to those described in infantile hemangiopericytoma, a rare neoplasm of vascular origin. By light microscopy the neoplasm was multilobular with highly proliferating round to spindle-shaped cells interspersed with numerous vascular spaces. Ultrastructurally, round to elongated cells with short processes, pinocytotic vesicles, reduplicated basal lamina, and basal lamina-like material were identified. Immunohistochemically the cells were weakly positive with antibodies to vimentin, focally positive with HHF-35, a smooth-muscle cell antibody, negative with antibodies to S-100 protein, T-200, neuron-specific enolase, neurofilaments, desmin, and cytokeratins 35BH11 and 34BE12. Blood vessels were positive with Ulexeuropaeuslectin, but tumor cells were negative. Reticulin stain decorated a delicate network of fibrils surrounding tumor cells and vascular spaces. Clinically the neoplasm did not recur and the baby has been disease free for more than 26 months. The difficulty of the histologic diagnosis of this neoplasm is discussed and the literature is reviewed, with special emphasis on lesions occurring in the oral cavity. PMID- 1518649 TI - Unusual oral presentation of non-Hodgkin's lymphoma in association with HIV infection. AB - In 4.4% of human immunodeficiency virus-associated non-Hodgkin's lymphoma the presenting lesion is seen in the mouth. Often the lesion may clinically resemble a less sinister process, and a definitive diagnosis of lymphoma may be delayed. We describe three unusual cases of non-Hodgkin's lymphoma, appearing intraorally in association with other oral lesions, in HIV-positive homosexual men. The three patients reported here were all diagnosed as having diffuse, large-cell malignant non-Hodgkin's lymphoma. We performed Epstein-Barr virus DNA in-situ hybridization on our cases and Epstein-Barr virus DNA sequences were not seen. We review the pertinent literature and stress the importance of including non-Hodgkin's lymphoma in the differential diagnosis of oral lesions in patients at risk of HIV infection. PMID- 1518650 TI - Efficacy of removing glass ionomer cement, zinc oxide eugenol, and epoxy resin sealers from retreated root canals. AB - Removal of gutta-percha and various sealers was assessed during retreatment of the root canal system. Sixty root canals were prepared and obturated with gutta percha and Ketac-endo, Roth's 801 cement, or AH26. After 14 days, the canals were retreated by hand or ultrasonic technique and the retreatment time was recorded. The roots were split and the amount of debris that remained on the canal walls in three separate levels was recorded by use of a dissecting microscope. The mean scores were compared by one-way and two-way ANOVA. The total score was significantly the highest for Ketac-endo (p less than 0.04), followed by AH26 and Roth's 801 cement. The largest amount of debris was consistently found in the apical third, and generally it was comparable for both retreatment techniques. The ultrasonic technique was significantly faster than the hand technique for all sealers tested (p less than 0.0004, p less than 0.0003, p less than 0.02, respectively). Hand retreatment of Ketac-endo was the slowest, whereas ultrasonic retreatment of Roth's 801 cement was the fastest. The results indicated that Ketac-endo endodontic sealer can be effectively removed from the root canal by ultrasonic instrumentation. PMID- 1518651 TI - In vivo comparison of the biocompatibility of two root canal sealers implanted into the mandibular bone of rabbits. AB - The purpose of this study was to evaluate the in vivo biocompatibility of two zinc oxide-eugenol-based sealers, Sealite and Pulp Canal Sealer, after implantation into the mandibular bone of rabbits. Thirty female New-Zealand rabbits were randomly divided into three groups on the basis of the material to be implanted in each side of the mandible: six rabbits received a positive control implant (silicone tubes filled with asbestos) in both sides of the mandible; 12 rabbits received a Sealite implant in the left side and a negative control implant (silicone tubes filled with silicone adhesive) in the right side of the mandible; and 12 rabbits received a silicone tube filled with Pulp Canal Sealer in the left side and a negative control implant in the right side of the mandible. The sealers were implanted in a freshly mixed, unset state. The rabbits were killed 4 or 12 weeks after implantation and the implants and surrounding bone were sectioned and treated in accord with standard histologic procedures. The tissue reactions were scored and rated as none, very slight, slight, moderate, severe, and very severe. The statistical analysis of the data showed that the two sealers had similar, good biocompatibility, and that the reactions observed at the 12-week period were better than those observed at the 4-week period. Both sealers may be used indifferently in routine endodontic practice. PMID- 1518652 TI - Which antibiotic? PMID- 1518653 TI - Preliminary evaluation of a digital system for rotational panoramic radiography. AB - A prototype system for direct digital panoramic radiography has been evaluated with respect to density, contrast, magnification, distortion, resolution, and overall image quality. Density and contrast depend on detector calibration and may be modified by the display system or by digital processing of the captured image. Variation of magnification in the horizontal and vertical dimensions gives rise to distortion phenomena that are identical to those encountered in film based systems. Resolution in the vertical dimension is determined by the pitch of the detector elements. In the horizontal dimension, resolution is limited by the effective width of the detector elements. To evaluate the clinical acceptability of the images, radiologists and general practice residents were asked to assess the perceptibility of important radiographic landmarks in film-based and digital images of both a radiographic phantom and a patient. The digital system performed on a par with film in the representation of normal morphologic structures of the clinical human subject whereas more differences were apparent in the phantom images. The general practice residents consistently rated the digital images higher than their radiologist counterparts did. No consistent trends were found to indicate any inherent deficiencies of the digital system in the depiction of any one area. The results indicate the promise of direct digital acquisition as a method of panoramic imaging. PMID- 1518654 TI - A radiologic study of pulmonary metastases originating from oral and maxillofacial tumors. AB - A retrospective clinical and radiologic study was carried out on 103 consecutive cases of oral and maxillofacial malignant conditions in which pulmonary metastasis occurred. The most frequent primary site was the palate. The neoplasm most commonly involved was the adenoid cystic carcinoma. Pulmonary metastases were classified into five types: solitary, multiple nodular, multiple "massy," diffuse, and miliary. PMID- 1518655 TI - Dosimetry of absorbed radiation in radiographic cephalometry. AB - Absorbed radiation was measured in various craniofacial tissues on an adult phantom (Alderson Rando) when conventional cephalometric radiographic techniques were used. The views examined were lateral, 45 degrees oblique, posteroanterior, lateral temporomandibular joint tomograph, and basilar (submental-vertex). Absorbed radiation was expressed in micrograys for the individual views and for combinations of views as customarily used in orthodontics and oral surgery. These data are compared with findings of contemporary investigators and the magnitude of the doses is compared with those in the literature for periapical and panoramic surveys. PMID- 1518656 TI - Calmodulin binding sites in the endolymphatic sac and stria vascularis of the human fetus and the guinea pig. AB - Calmodulin (CaM) binding sites, which are available and unoccupied by CaM at the time of fixation, were analyzed in the guinea pig endolymphatic sac and stria vascularis using CaM conjugated tetramethyl rhodamine isothiocyanate. The endolymphatic sac epithelium and stria vascularis both showed strong fluorescence. Weak CaM binding sites were seen in the endolymphatic sac in the 12 week-old human fetus. In contrast, the fluorescent reaction in the stria vascularis and endolymphatic sac in 14- and 15-week-old human fetuses was strong. These results suggest that CaM may play an important role for the maintenance of ionic stability in the endolymph. PMID- 1518657 TI - The length of isolated outer hair cells is temperature dependent. AB - In the mammalian cochlea, motile properties of outer hair cells may contribute to sharp tuning and amplification. Length changes of isolated outer hair cells in response to various physical and chemical stimuli have therefore been investigated by many laboratories. The present study shows that alteration of temperature changes the length of outer hair cells of the guinea pig cochlea as much as 0.22 micron/degrees C. Thus, length changes in response to alterations of temperature are similar to length changes in response to other physical and chemical stimuli. PMID- 1518658 TI - Histochemical localization of glycoconjugates in the developing endolymphatic sac and vestibular end organs of the mouse. AB - The distribution of glycoconjugates in the endolymphatic sac (ES) and vestibular end organs from the 12th gestational day (GD) in the developing mouse to the 6th day after birth was analyzed using six biotinylated lectins: wheat germ agglutinin (WGA), Abrus precatorius agglutinin (APA), Ulex europaeus agglutinin I (UEA-I), Ricinus communis agglutinin 120 (RCA120), Helix pomatia agglutinin (HPA), concanavalin A (conA). In the 13th and 15th GD sections, the luminal contents in the fetal ES were strongly labelled with lectins, while only a small amount of substance in the ES was labelled with lectins after the 17th GD. In the 13th GD sections, before the cupula and otoconia were formed, the fetal ES started to produce glycoconjugates labelled with WGA, APA, RCA120 and ConA. In the 17th GD sections, the immature cupula and otoconia were strongly labelled with WGA, APA and RCA120. Sugar residues stained by lectins detected in the substance of the fetal ES were the same as those found in the immature cupula and otoconia. HPA only stained the ES epithelium around the 13th and 15th GD. The fetal ES may interact with the formation of the cupula and otoconia, especially in the early stage during evolution and that HPA-reactive glycoconjugates may be related to the intracellular elements of the ES epithelium only during a well defined phase of development. PMID- 1518659 TI - Effect of ambroxol on rabbit eustachian tube surfactant. AB - The effect of ambroxol administration on phospholipid and phosphatidyl-choline contents of rabbit eustachian tube and lung washings and on [14C]-choline incorporation by rabbit eustachian tube and lung tissue has been studied. Despite minor differences, the drug exerts the same activating effect in both locations. The results add a further piece of evidence to the several similarities existing between the lung surfactant and the surface-active substances present on the eustachian tube. PMID- 1518660 TI - Evaluation of the galvanic vestibulo-ocular response recorded with a modified electronystagmographic technique. AB - Previously, a simple method for recording galvanic nystagmus (GN) using conventional electronystagmography (ENG) was demonstrated. The present study reports on investigations made to examine the applicability of that technique. During a standard stimulus over 20 s, amplitudes and rate of saccades show no tendency to diminish. In a series of 10 repeated standard stimuli over 16 min, a parabolic relationship is observed between time on one side and on the other, the mean amplitude, the mean rate of saccades and the sum of amplitudes per stimulus duration. The threshold of GN was 1.29 mA and that of induced tilting sensation 3.64 mA. In a series of 8 repeated threshold stimuli, thresholds of GN and tilting sensation linearly increase (p less than 0.001). During the slow increase of the current, the amplitudes and frequency of saccades and the slow-phase velocity linearly increase (p less than 0.01). The direction of per- and poststimulatory galvanic nystagmus and tilting sensation were investigated. Several autonomic reactions and psychophysical sensations during stimulation were noted. In conclusion, it is thought that the modified ENG technique is a valid method for further clinical use and basic research and its applicability has proven to be good. PMID- 1518661 TI - Diagnosis of cerebellopontine angle tumors. AB - Between 1980 and 1990, 9,176 patients suffering from otoneurological disorders were investigated in our clinic. Sixty-six (0.72%) internal auditory canal or other cerebellopontine angle tumors (CPAT) were diagnosed. Brainstem auditory evoked potentials (BAEP), interaural time discrimination, and magnetic resonance imaging (MRI) revealed to be the most sensitive and efficient tests for the detection of CPAT. However, the investigation of otoneurological symptoms cannot be limited to BAEP and MRI on the a priori of a hypothetical CPAT. Electrophysiologic tests such as impedancemetry, and electronystagmographic testing are also needed to elucidate the many causes of otoneurological symptoms. PMID- 1518662 TI - Middle ear inflation with a gas mixture. AB - We studied the middle ear (ME) pressure in 13 atelectatic ears to evaluate the effect of politzerization or ME inflation by a catheter using both room air and a gas mixture. The gas contained 12% O2, 6% CO2 and 82% N2. Tympanometry was performed before and after the treatment. The elevated ME pressure induced by the treatments, whether with room air or the gas mixture, declined rapidly within the first 30 min. However, at 35 and 45 min after the treatment with room air, the mean decrease in pressure was significantly greater than with the gas mixture, which might be due to slow oxygen absorption through the ME mucosa. PMID- 1518663 TI - Cochlear function after stapedectomy. AB - The short-term and long-term results of stapedectomy for eliminating the conductive element and improving the hearing in patients with otosclerosis are highly satisfactory all over the world. The delayed sensorineural hearing loss which continues after successful stapedectomy may be due to the operation itself or due to the natural history of the disease. The study was conducted on 80 patients with unilateral stapedectomy with a minimal follow-up period of 1 year. We found that bone conduction values at each frequency in operated ears were stable with marked improvement at 2,000 Hz, on the other hand, the bone conduction thresholds in non-operated ears significantly deteriorated (p less than 0.001). The speech discrimination score was significantly improved in the operated group (p less than 0.001). An explanation for the cochlear changes in operated and non-operated ears is presented. PMID- 1518664 TI - Effect of H2-blockers, cimetidine and famotidine, on histamine nasal provocative test. AB - The H2-receptor is considered to mediate the stabilization of the membrane of mast cells by enhancing cAMP synthesis. In the present study, we investigated the effect of H2-receptor antagonists, i.e. H2-blockers, on nasal hypersensitivity using a histamine nasal provocative test. A 7-day administration of cimetidine tended to lower the histamine threshold. Famotidine administered in the same way caused no significant decrease in the histamine threshold. Based on the above results, we postulate that famotidine should be preferred to cimetidine as an H2 blocker in patients with gastric and/or duodenal ulcers. PMID- 1518665 TI - Direct observation of living laryngeal carcinoma cells during invasion of healthy cell formation. AB - After cloning of laryngeal carcinoma cells from tumor fragments obtained during surgery, the behavior of pure tumor cells was investigated under the inverted microscope. In tissue culture flasks, separately grown tumor cell layers and fibroblast layers were cocultured to visualize the invasion of malignant cells into healthy tissue. Using a time-lapse camera, the cells were recorded. The tumor cells often penetrated the healthy cell formation in a wedge-shaped cell formation. Near the tumor front, an elevated cell motility was found accompanied by continuous changes in the cell shape. Intercellular gaps were broader in the front line than in the more posterior parts of the tumor cell formation. The profound motility of the carcinoma cell enabled selected cells to leave the tumor cell formation completely and to migrate as single cells through healthy tissue. Eventually, some of the single tumor cells migrating through the fibroblast layer moved back to the tumor cell formation. Thus they left healthy appearing tissue behind which was earlier infiltrated by a malignant cell. PMID- 1518666 TI - Ventricular fibrillation following local application of cocaine and epinephrine for nasal surgery. AB - We report the case of a 17-year-old female patient, scheduled for septoplasty under general anesthesia, who developed ventricular fibrillation after intranasal application of cocaine (350 mg) and submucosal injection of lidocaine (20 mg) with epinephrine (100 micrograms). Resuscitation by external chest compression was successful, and normal sinus rhythm was reestablished after lidocaine injection (50 mg, i.v.). The cardiac risk of the combined administration of cocaine and epinephrine during general anesthesia are discussed. PMID- 1518667 TI - Laryngeal paraganglioma and pregnancy. AB - Paraganglioma is an uncommon tumor of the larynx. We present a 30-year-old woman with a paraganglioma which took a heretofore not described clinical course. The first clinical sign was persistent hoarseness, when she was 26 weeks pregnant. A histological examination of a piece of the reddish, racemose tumor removed during microlaryngoscopy revealed only some slight nonspecific inflammatory changes. The patient remained free of symptoms following this operative procedure until 3 years later when she presented with a recurrence of hoarseness and a laryngeal tumor and was 25 weeks pregnant. Histology showed a laryngeal paraganglioma in the same supraglottic localization as before. Histological studies failed to confirm the obvious suspicion that the episodic growth of the paraganglioma may have been induced by estrogen or gestagen. To date, 6 years after the removal of the tumor, there has been no recurrence. PMID- 1518668 TI - Little things we take for granted. PMID- 1518670 TI - Comparison of preparation and narcotic-sedative premedication in children undergoing surgery. AB - A psychological preparation program was developed for use prior to emergency surgery in children. The purpose of this study was to test the hypothesis that provision of specific information prior to an emergency operation would reduce the need for premedication to control anxiety and stress. Children were randomly assigned to either a verbally prepared group given narcotic-sedative premedication (control) or to a psychologically prepared group given only atropine as premedication. The child and parent rated their own anxiety on a Visual Analogue Scale (VAS). The children and parents were also assessed by a nurse preoperatively and postoperatively using a similar scale. The children's pulse, blood pressure, and cortisol were also measured. The results showed no significant difference between the psychologically prepared group and the premedicated group, suggesting that psychological preparation compares favorably with narcotic-sedative premedication. PMID- 1518669 TI - Parenting enhancement among Egyptian mothers in a tertiary care setting. AB - This study tested the efficacy and effectiveness of systematically planned parenting enhancement program aimed toward breaking the cycle of high-risk mothers producing high-risk babies in Egypt. The assumption is that self-esteem and self-care are requisites to effective parenting, which can be enhanced or impeded by human and environmental forces. Given that parenting is a learned behavior, it can be repatterned by modifying human-environmental processes. PMID- 1518671 TI - The reactions of Chinese children who have cancer. AB - While many studies have explored the impact of childhood cancer on children and their families, few articles have examined the effects of this disease on selected cultural groups. Reactions of children and families in a select group from the People's Republic of China are described. PMID- 1518672 TI - Factors influencing visits to school nurses by pregnant adolescents. AB - The influence of five factors on the first visit to school nurses by pregnant adolescents and adequacy of prenatal care was analyzed. Only one factor, age of baby's father, was found to be associated with adequacy of prenatal care. PMID- 1518673 TI - The 'acting-out' adolescent: identification and management. AB - The 'acting-out' adolescent presents both challenges and problems to the pediatric nurse who may not have the psychiatric skills necessary for managing negative behaviors that can interfere with both the adolescent's treatment and the overall functioning of the unit. Basic information is presented that will assist the pediatric nurse in the assessment and intervention of adolescents who present with problems manifested by behaviors related to anxiety, anger, hostility, and aggression. PMID- 1518674 TI - Measles: again an epidemic. AB - With the incidence of measles again on the rise in the United States, nurses have important roles in health promotion and education. Nurses and other health care providers need to be well informed about the potential severity of measles and the importance of immunization in preventing measles. PMID- 1518675 TI - An overnight retreat to facilitate coping with stress. AB - Stress is an ever-present part of nurses' work and personal lives. In an effort to facilitate coping with this stress, a diverse group of staff came together to plan what ended up being a unique and thoroughly beneficial experience. PMID- 1518676 TI - Pediatric management problems: yeast infections. PMID- 1518677 TI - Prevention of childhood injuries. Part I: Motor vehicle injuries. AB - Unintentional (accidental) injuries are the leading cause of death in childhood and adolescence. In this article, interventions to reduce death and disability among children from motor vehicle injuries are identified. The major categories of injury are listed, the magnitude of the problem is defined, the risk factors are described, and selected interventions of the National Committee for Injury Prevention and Control are summarized. Recommendations for practice are discussed. PMID- 1518678 TI - New OSHA regulations regarding HBV vaccination. PMID- 1518679 TI - Faculty practice: an opinion. PMID- 1518680 TI - Clinical practice guidelines: treatment of otitis media in children. PMID- 1518681 TI - Relationship between apnea and GER: what nurses need to know. AB - Apnea and gastroesophageal reflux (GER) are both common occurrences in newborns and infants as well as in older children. There is a strong relationship between them. The correlation between GER as a cause of apnea has become increasingly clear over time. The extent to which they occur is an important subject for nurses in terms of recognition and intervention. PMID- 1518682 TI - Parent and infant attachment: review of nursing research 1981-1990. AB - PURPOSE: To determine what research information on attachment and bonding is available to nurses. METHOD: A critical review was conducted for 26 studies on attachment and bonding published between 1981-1990. FINDINGS: Studies had strength in their consideration of multiple factors hypothesized to influence attachment and bonding. However, methodological concerns are raised about validity of designs and tools. CONCLUSIONS: Nurses involved in clinical practice and research would benefit by clarifying their conceptions of attachment and bonding. Nurses can broaden their assessment base, including fathers' as well as mothers' perspectives, verbal and nonverbal behaviors, cultural differences, and interchange in the parent-infant relationship. PMID- 1518683 TI - Acetaminophen and ibuprofen: fever control and overdose. AB - Fever has been recognized as a sign of disease for centuries. Health care professionals and parents frequently search for new methods of pediatric fever control. Current research suggests that prostaglandins play an important role in fever production. As antipyretics, both acetaminophen and ibuprofen are effective in fever reduction by inhibiting prostaglandin synthesis. In this article, the pathophysiology of fever is discussed as a foundation for understanding fever management. The metabolic pathways of both agents are compared as they relate to fever control; the common side effects and nursing management for acute overdoses are discussed. PMID- 1518684 TI - Cigarette, alcohol, and other drug use by school-age pregnant adolescents: prevalence, detection, and associated risk factors. AB - Use of cigarettes, alcohol, and other drugs among pregnant adolescents is just beginning to be documented. This study sought to determine the prevalence and associated risk factors of cigarette, alcohol, and other drug use among school age adolescents attending a comprehensive teenage pregnancy program. All enrollees completed a self-administered questionnaire and provided a breath sample for carbon monoxide analysis. Urine was obtained for quantitative determination of drug metabolites at the initial and one third-trimester visit. A chart review determined medical provider recognition of cigarette, alcohol, and other drug use. Results were analyzed for 93% of 229 eligible patients. Seventeen percent were positive for alcohol or other drug use by questionnaire self-report, provider report, or initial urine screen. Eleven percent were positive by urine screen alone at either the initial or third-trimester visit. Medical providers were successful in identifying nearly all of the cigarette smokers, but fewer than half of the alcohol drinkers and few of the other drug users. Forward stepwise multiple regression determined the most efficient model for predicting alcohol and other drug use. A report of having been high at school and personal or friends' use of cigarettes were the most significant risk factors. Results indicate a high prevalence of alcohol and other drug use and suggest a need for changes in current practice related to the detection and management of such drug use in pregnant adolescents. PMID- 1518685 TI - Parents' views of adolescent health issues. AB - To determine how important the parents of teenagers consider adolescent health issues to be and the kind of involvement they would like from their schools and physicians, a questionnaire was sent to 1090 families with children attending two public high schools in a suburban community. The 438 parents who completed the questionnaire (40% response rate) indicated that their adolescents had a mean age of 16.2 years, 52% were male, 54% were in grades 11 and 12, and 70% received regular care from a pediatrician. Most parents considered substance use, sexuality, mental health issues, nutritional concerns, and general medical issues to be issues requiring attention nationally; many considered these issues to require attention locally; fewer considered these issues to require attention for their teenager's friends; and only some indicated these issues require attention for their own teenagers. More than 95% of respondents said parents should discuss these topics with their teenagers, more than 80% said they themselves did, and more than 85% said they wanted these issues discussed with their adolescents in school. Approximately three quarters of parents said that they would bring their adolescent to their regular doctor for management of these issues, expected that their physician would be comfortable with such care, and wanted their doctor to discuss these issues with their teenagers.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1518686 TI - Maternal smoking and behavior problems of children. AB - Numerous health consequences of children's exposure to maternal smoking have been demonstrated, including increased rates of low birth weight, infant mortality, respiratory infections, asthma, and modest impairments of cognitive development. There is little evidence, however, linking maternal smoking and increased rates of children's behavior problems. Data from the population-based National Longitudinal Survey of Youth were used to investigate the possible association of maternal smoking and behavior problems among 2256 children aged 4 through 11 years. In multiple regression analyses the authors controlled for child's race, age, sex, birth weight, and chronic asthma; family structure, income, and divorce or separation in the prior 2 years; mother's education, intelligence, self esteem, employment status, chronic disabling health conditions, and use of alcohol during pregnancy; and the quality of the home environment as assessed by the Home Observation for Measurement of the Environment-Short Form to investigate the relationship between maternal smoking and children's behavior problems. The measure of maternal smoking status reflected two levels of smoking intensity (less than a pack per day and a pack or more per day) for each of three different categories of children's exposure: prenatal only (mother smoked only during pregnancy), passive only (mother smoked only after pregnancy), and prenatal plus passive exposure (mother smoked both during and after pregnancy). Measures of children's behavior problems included the overall score on a 32-item parent reported child Behavior Problem Index (PBI), scores on the BPI's subscales, and rates of extreme scores on the BPI.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1518687 TI - Chest pain in otherwise healthy children and adolescents is frequently caused by exercise-induced asthma. AB - Chest pain in children and adolescents, unlike in adults, is rarely of cardiac origin and its etiology is frequently unknown. In this age group, chest pain can limit normal activity and sports participation. The reported incidence of exercise-induced asthma in children with chest pain is less than 20%. For this study, 88 otherwise healthy children and adolescents with chest pain followed a treadmill protocol without a warm-up period designed to obtain a target heart rate of 180 or greater during the first several minutes of exercise. Patients maintained this workload for 6 to 8 minutes. Pulmonary function tests performed prior to exercise and at 2, 5, 10, 15, 20, and 25 minutes revealed a decrease in forced expiratory volume in 1 second or peak expiratory flow rate of greater than or equal to 15% in 64 (72.7%) children. Inhaled albuterol resulted in subjective improvement in 97% (35/36) and objective improvement in 70% (25/36) of patients. In otherwise healthy children and adolescents with chest pain, the incidence of exercise-induced asthma seems greater than previously reported. Treatment with bronchodilators may help these patients lead a more active life-style. PMID- 1518688 TI - Correlates of children's bicycle helmet use and short-term failure of school level interventions. AB - To test the utility of school-level interventions for child bicycle safety and to identify social and behavioral factors associated with children's bicycle helmet use, a two-level intervention was conducted in two suburban elementary schools. Children (N = 209) and parents (N = 125) in school 1 and in school 2 (children, N = 470; parents, N = 364) were surveyed regarding bicycle injuries and helmet use. Children and parents in schools 1 and 2 received literature about bicycle safety and discount coupons for helmet purchase. School 1 was then the target of an intensive safety campaign, including meetings with the school safety committee and the PTA and a classroom presentation to children emphasizing helmet use. Ten months later the same survey was again administered. Children in school 1 were more likely at posttest to believe that helmets were protective (P = .003) but did not differ on other variables. Logistic regression showed that sibling helmet ownership, parental helmet use, and lower parental perceived social barriers to helmet use were independently associated with children's reported helmet use and with parental intent for the child to use a helmet at posttest. PMID- 1518689 TI - Above and below the threshold: severity of psychiatric symptoms and functional impairment in a pediatric sample. AB - Pediatricians are sufficiently concerned about the importance of "subthreshold" mental health problems to have joined in the movement to create a Diagnostic and Statistical Manual of Mental Disorders for the primary care setting (DSM-PC), with the aim of establishing a set of criteria for disorders that do not meet the severity requirements of the American Psychiatric Association's current DSM. An element in the argument for a DSM-PC is that there is a high level of functional impairment and need for treatment in children with mental health problems below the DSM threshold. This was examined in 789 children aged 7 through 11 recruited sequentially from the pediatric clinics of a health maintenance organization, compared with 134 age-matched children seen in a psychiatric clinic. Of the pediatric patients, 22% had one or more clinical-level DSM-III diagnoses, and 42% had a threshold-level disorder, compared with 65% and 34%, respectively, of psychiatric patients. In the pediatric sample, most threshold, and all clinical level disruptive behavior disorders were associated with significant levels of functional impairment. There was little evidence that emotional disorders (anxiety and depression), even at the clinical level, were associated with significant impairment. One implication of these results is that pediatricians can expect one child in five to have a clinical-level DSM disorder. A second is that intervention at low levels of disruptive behavioral symptomatology may be needed if significant functional impairment is to be avoided. PMID- 1518690 TI - Mother-to-child transmission of human immunodeficiency virus type 1: risk of infection and correlates of transmission. AB - One thousand eight hundred eighty-seven children born to human immunodeficiency virus type 1 (HIV-1) seropositive mothers, including 1045 infants prospectively followed up from birth, were studied. Intravenous drug use was the most frequent maternal risk factor, although the percentage of women infected by sexual contact increased from 5.8% in 1985 to 28.5% in 1990. Of the 551 first children followed up from birth and older than 15 months of age, 101 (18.3%) acquired infection and seroconverted to HIV-1. Another 31 (5.6%) asymptomatic seronegative children showed the presence of viral markers, for an apparent mother-to-offspring transmission rate of 23.9%. Overlapping results were seen in 22 second-born children followed up from birth. Of 59 sibships with definite infection status, when the first child was infected, 14 (40%) of 35 second children were infected, whereas when the first child was not infected, only 2 of 24 (8.3%) second children were infected. Discordance in HIV-1 transmission was found in 1 of 18 pairs of twins. Univariate and multivariate analyses of possible risk factors for HIV-1 transmission performed on the entire population of children and in the cohort of those followed up from birth were basically in agreement in indicating that the development of symptoms in the mother before delivery and breast-feeding (indeed adopted in only 22 infants in whom HIV-1 infection was identified at birth) were significantly and independently associated with a higher transmission rate. In addition, girls were more frequently infected than boys.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1518691 TI - Iron status in exclusively breast-fed infants. AB - The aim of this study is to evaluate the iron nutritional status of infants breast-fed exclusively and for a prolonged period in relation to their growth rate and dietary changes. Forty subjects (25 breast-fed; 15 formula-fed) were studied from 0 to 9 months of age. Milk (human or formula) was the only source of food during the first 6 months. From the sixth month onward mothers were instructed to use iron- and ascorbic acid-rich foods to supplement breast feeding. At the ninth month, prevalence of anemia was 27.8% in the breast-fed group and 7.1% in the formula-fed group. Storage iron was absent in 27.8% of the breast-fed infants vs none of the formula-fed infants. These findings reinforce the recommendation that breast-fed infants be given supplemental iron from the fourth month of life. PMID- 1518692 TI - Oxygen desaturation complicates feeding in infants with bronchopulmonary dysplasia after discharge. AB - Recurrent episodes of hypoxemia may affect the growth, cardiac function, neurologic outcome, and survival of infants with bronchopulmonary dysplasia (BPD). As oral feeding might stress these infants by compromising pulmonary function even after hospital discharge, we measured oxygen saturation (SaO2) via pulse oximetry before, during the initial 10 minutes of, and immediately after oral feeding in 11 patients with BPD, 12 very low birth weight infants, and 23 healthy full-term infants. All infants with BPD had been previously discharged from the hospital after weaning from supplemental oxygen. Studies were done at a mean postconceptional age of 43 weeks while the infants were fed at home by one of their parents. Levels of SaO2 for the three groups were comparable before and during feeds. After feeding, the infants with BPD had significantly lower mean levels of SaO2 (84 +/- 8% [SD] vs 93 +/- 4% and 93 +/- 3%, respectively; P less than .01). They also spent more time after feeding with an SaO2 less than 90% (64 +/- 34% of time vs 27 +/- 33% for the very low birth weight and 22 +/- 20% for the term group; P less than .01) and greater time with an SaO2 less than 80% (37 +/- 28% vs 4 +/- 10% and 4 +/- 8%, respectively; P less than .01). Desaturation in infants with BPD was related to larger volume and faster oral intake during feeding. Thus, the data indicate that desaturation after feeding remains a recurrent problem for survivors of BPD after discharge.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1518693 TI - Potential role of intrapulmonary shunting in the genesis of hypoxemic episodes in infants and young children. AB - A number of physiologic phenomena during some apneic/cyanotic episodes in infants and young children cannot be explained sufficiently on the basis of a cessation or reduction in alveolar ventilation alone. These include (1) the extremely rapid development of hypoxemia during some episodes, (2) the occurrence of hypoxemic episodes despite continuous ventilation, (3) differences in the speed of desaturation between different forms of apneic episodes, (4) the presence of continued breathing efforts and yet absent airflow despite bypass of the upper airway, and (5) evidence that apnea and hypoxemia may begin simultaneously. Potential mechanisms to explain these phenomena include the sudden development of an unevenness in the matching between ventilation and lung perfusion, the flow of blood through unventilated areas of lung, and a sudden impairment in gas diffusion. Evidence from physiological and morphological studies suggests that all of these mechanisms, although to a different extent, may be involved in apneic/cyanotic episodes. The recognition that nonapneic mechanisms can cause sudden profound hypoxemia may alter our approach to the identification, treatment, and prevention of these episodes. PMID- 1518694 TI - Hearing and neurodevelopmental outcome in survivors of persistent pulmonary hypertension of the newborn. AB - Thirty-four infants who had a diagnosis of severe persistent pulmonary hypertension of the newborn at birth (alveolar-arterial oxygen difference greater than 600) were treated without paralysis or hyperventilation to induce alkalosis. All survived. Twenty-seven of these 34 eligible infants (79%) underwent neurologic, intelligence, and audiologic testing between 10 months and 6 years of age. Children who were younger than 1 year of age at the initial hearing test were retested after they reached 2 years of age. The average IQ was within the normal range (mean = 96.23). None had sensorineural hearing loss. Severe neurologic abnormalities were seen in 4 children, 3 of whom had been severely asphyxiated at birth (determined by biochemical criteria). Mild neurologic abnormalities were observed in 5 children. Two infants had bronchopulmonary dysplasia because they required supplemental oxygen for 29 and 66 days, respectively, and had abnormal chest roentgenograms; 1 patient takes intermittent doses of albuterol (Ventolin) and neither currently requires supplemental oxygen. This study of 27 infants with severe persistent pulmonary hypertension of the newborn suggests that conservative management without induced alkalosis or respiratory paralysis is accompanied by no sensorineural hearing loss and a good neurologic outcome. PMID- 1518695 TI - Clinical diagnosis and management of respiratory distress in preterm neonates: effect of participation in a controlled trial. AB - The ability to generalize the results of a clinical trial depends on the ability to compare a population of patients with the population described in the trial, emphasizing the importance of objective diagnostic criteria in study design and clinical medicine. However, clinical decisions are often based on subjective interpretations of data. There is concern that bias that an experimental therapy is beneficial might lead to alterations in clinical diagnosis and management. To evaluate this concern, the authors reviewed a preexisting database comprising information obtained by trained personnel by chart review to investigate prospectively the frequency of the diagnosis of hyaline membrane disease and the use of mechanical ventilation before and during participation in a clinical trial of surfactant therapy during which such therapy was available exclusively through clinical trials. Major eligibility criteria for a randomized trial at the Medical University of South Carolina included mechanical ventilation and the diagnosis of hyaline membrane disease. Both the diagnosis of hyaline membrane disease and the use of mechanical ventilation increased between pre-surfactant and randomized trial periods (hyaline: 47.2% to 55.9%, P less than .05; ventilation: 55.6% to 66.3%, P less than .01). The possibility that enthusiasm for surfactant influenced clinical diagnosis and management of respiratory distress during this period cannot be dismissed. PMID- 1518696 TI - Neonatal hyperbilirubinemia associated with glucose-6-phosphate dehydrogenase deficiency in Sephardic-Jewish neonates: incidence, severity, and the effect of phototherapy. AB - Glucose-6-phosphate dehydrogenase (G-6-PD) deficiency is frequently associated with neonatal hyperbilirubinemia, and sometimes kernicterus, often in the absence of any identifiable trigger or hematological evidence of hemolysis. The aim of this study was to compare the incidence and severity of, and the effect of phototherapy on, jaundice in G 6-PD-deficient vs G-6-PD-normal neonates in the Sephardic-Jewish community. Healthy term newborns, born to mothers of families stemming from geographic areas known to be "at risk" for G-6-PD deficiency, were screened for the condition and surveyed for hyperbilirubinemia. Seventy-five G-6 PD-deficient neonates formed the study group, while 266 neonates with normal levels of the enzyme formed the control group. Neonates with any other identifiable cause for jaundice were excluded. Phototherapy was commenced when the serum bilirubin levels reached 16 mg/dL (274 mumol/L) or more, and it was discontinued at 12 mg/dL (205 mumol/L) or less. Hyperbilirubinemia developed in 27 (36%) of the deficient neonates (serum total bilirubin greater than 13.9 mg/dL [238 mumol/L]), compared with 50 (18.8%) of control neonates (P = .002), while 20 (26.7%) of the study group required phototherapy, compared with 31 (11.7%) of control neonates (P = .002). Two neonates in the study group required exchange transfusion (serum bilirubin greater than 20 mg/dL [342 mumol/L]), vs 0 in the control group (not significant).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1518697 TI - Community-based evaluation of the effect of breast-feeding on the risk of microbiologically confirmed or clinically presumptive shigellosis in Bangladeshi children. AB - To assess the association between breast-feeding and the risk of microbiologically confirmed or clinically presumptive shigellosis, the authors performed a case-control analysis of Bangladeshi children younger than 3 years of age who were followed up for 1 month after exposure to Shigella in their residential neighborhoods. Two hundred sixty-nine cases with culture-confirmed shigellosis (n = 119) or clinically presumptive shigellosis (culture-negative dysentery, n = 150) were compared with 819 controls without Shigella diarrhea or other invasive diarrheal illnesses. The odds ratio relating breast-feeding to confirmed or presumptive shigellosis, adjusted for potentially confounding variables, was 0.48 (95% confidence interval = 0.32 to 0.72; P less than .001), suggesting a substantial protective effect. The protective association decreased with age but was still significant during the third year of life; appeared to be directly related to the degree of stunting; and was equivalent for confirmed and presumptive shigellosis. Notably, the protective association remained substantial against episodes due to Shigella which were resistant to at least one of the antibiotics customarily used for treatment of Shigella diarrhea (age-adjusted odds ratio = 0.40; 95% confidence interval = 0.22 to 0.74; P less than .01). These data suggest that breast-feeding confers a high level of protection against shigellosis throughout the first 3 years of life, especially among nutritionally compromised children, and thereby underscore the importance of promotion of breast-feeding as a central component of Shigella control programs in less developed settings. PMID- 1518698 TI - Microwave heating of infant formula: a dilemma resolved. AB - Microwave heating of infant formula is a common practice despite concerns of infant scalding. Beyond the issue of physical safety, little is known about the effects on nutrient content of microwave heating of infant formula. Casein predominant infant formula in 120- and 240-mL glass and plastic nursing bottles of varying colors were heated for 40 seconds and 60 seconds, respectively. Temperature profiling was monitored during the heating cycle. Analysis of riboflavin and vitamin C was made prior to and after heating. Topmost portions reached a mean temperature of 44.7 +/- 1.7 degrees C and 43.0 +/- 2.4 degrees C for all types of 240-mL and 120-mL bottles, respectively. Topmost temperatures were significantly hotter than temperatures reached at other sites. Routine mixing resulted in formula temperatures which could safely be fed to infants (35.4 +/- 0.3 degrees C and 33.9 +/- 0.2 degrees C for 240-mL and 120-mL bottles, respectively). There was no significant loss of either riboflavin or vitamin C. Protocols for microwave heating are given. PMID- 1518699 TI - Brush-culture method for diagnosing tinea capitis. AB - Using traditional methods to verify the existence of a fungal infection in children with suspected tinea capitis is a cumbersome process. Scraping scale and pulling hairs for culture or microscopic examination can be time-consuming and uncomfortable for the child. This study is the first comparison of this method with an alternate brush-culture method for diagnosing tinea capitis. In 70 children with symptoms suggestive of tinea capitis, there was strong agreement between methods in detecting disease or lack thereof (McNemar's test, P less than .2). In the 51 paired positive cultures, those obtained by brush culture turned positive significantly faster (t test, P less than .01) than samples obtained by the traditional method. The brush method is a reliable, painless, and more expedient way to obtain cultures from children with suspected tinea capitis. PMID- 1518700 TI - Abraham Jacobi Award address, April 14, 1992 the medical home: pediatric practice and child advocacy in the 1990s. PMID- 1518701 TI - Growth and development of children conceived by in vitro fertilization. AB - To assess the physical and mental development of infants born after in vitro fertilization (IVF), we performed a general physical and developmental examination (Bayley and Stanford-Binet scales) on a cohort of 116 IVF children, conceived and born at our institution between February 1985 and March 1989, and on 116 non-IVF matched controls. Study and control groups were each composed of 66 singletons, 19 pairs of twins and 4 sets of triplets, whose age at examination ranged from 12 to 45 months. The developmental indices of IVF infants were within the normal range and did not differ from those of their matched controls. The indices were positively correlated to gestational age, birth weight, head circumference at birth and at examination, and mother's education. Mean birth weight, gestational age, and birth weight percentile of IVF infants were lower than the mean of the healthy population. Mean percentiles of weight and length at examination (mean age 22.4 months) were equally low but did not differ from those of the matched controls. However, mean percentiles of head circumference at birth and at examination compare well with the normal mean, both in IVF and control groups. Twins and triplets (IVF and controls) had significantly lower physical and mental indices as compared to singletons. PMID- 1518702 TI - Effect of maternal hypertension on neonatal neutropenia and risk of nosocomial infection. AB - Neonatal neutropenia occurs in approximately 50% of newborns delivered by women with pregnancy-induced hypertension. It is thought to be transient, independent of birth weight and gestational age, and unassociated with significant risks, including infection. It recently was suggested that neonatal neutropenia occurs primarily in smaller, younger neonates, is related to the severity of pregnancy induced hypertension, and importantly, may be associated with an increased risk for nosocomial infection. We examined these points in a large inborn population in consecutive years, performing retrospective (n = 110, 1989) and prospective (n = 151, 1990) studies in low birth weight (less than or equal to 2200 g) neonates delivered by women with pregnancy-induced hypertension. Overall, 40% to 50% of neonates studied developed neonatal neutropenia, and they were younger and smaller (P less than .01) than non-neutropenic neonates. In the prospective study, neutropenic neonates were more likely to have mothers with severe pregnancy-induced hypertension (P less than .001), and the incidence of neonatal neutropenia was primarily among neonates less than 30 weeks of gestation and less than 1500 g birth weight, approximately 80% vs 35% to 45% in older, larger neonates or infants (P less than .001). Although nosocomial infection occurred more frequently among the group of neutropenic neonates in the prospective study (P less than .02), the incidence was similar to that in matched non-neutropenic controls delivered of normotensive women. Thrombocytopenia (less than 100,000/mm3) was not more frequent in neutropenic neonates.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1518703 TI - Diagnostic imaging in the evaluation of the first urinary tract infection in infants and young children. AB - The evaluation of infants and children after the first urinary tract infection has undergone change in recent years. Standard diagnostic imaging studies are being utilized on a more frequent basis, because these procedures can provide information which often has a direct impact on patient care. Selection of the proper tests requires an understanding of how they are performed and the basis for their choice. The rationale for the use of different imaging studies and their application to patient care are discussed. PMID- 1518705 TI - A prospective study of cognitive functioning following low-dose cranial radiation for bone marrow transplantation. AB - This study prospectively examined the effects of low doses of cranial irradiation on psychological development in children. The subjects were 22 children receiving bone marrow transplantation. Fifteen children receiving cranial doses ranging from 350 to 1200 cGy as part of their conditioning regimen were contrasted to seven children who were not irradiated. Measures of intellectual and psychosocial development were administered to all subjects prior to transplant and again at one-year posttransplant. There were no decrements in psychological functioning at the one-year follow-up, regardless of the dose of cranial radiation received or the age at which radiation was administered. In addition, there were no significant differences in test scores relative to baseline in a smaller cohort of children followed up for 3 years. Although no significant between-group findings were found, examination of individual cases revealed a high degree of variability, with decrements in IQ of 10 points or more found in 7 children at the one-year follow-up. Findings suggest that doses less than 1500 cGy may prove to be relatively well tolerated with respect to long-term cognitive and psychosocial development, even in young children, although caution is urged in light of the limited length of follow-up. PMID- 1518704 TI - Urine sodium excretion in response to an oral glucose tolerance test in obese and nonobese adolescents. AB - To determine if physiologic changes of insulin are capable of inducing sodium retention in insulin-resistant patients, we evaluated the ability of an oral glucose tolerance test to alter urine sodium excretion in 32 obese subjects (13.3 +/- 1 years, weight 82 +/- 5 kg, mean arterial pressure 89.3 +/- 1.5 mm Hg) and 13 nonobese subjects (13.8 +/- 2 years, weight 46 +/- 4 kg, mean arterial pressure 74.5 +/- 2.6 mm Hg). After an overnight fast, subjects were placed in water diuresis and fasting insulin and glucose levels were drawn. Three 30-minute urine collections were obtained for baseline urine sodium excretion. The oral glucose tolerance test was administered with glucose and insulin levels drawn at 15, 30, 45, 60, 90, and 120 minutes. During the oral glucose tolerance test, four 30-minute urine collections were obtained for urine sodium excretion. Serum glucose levels at baseline and throughout the glucose tolerance test did not differ between obese and nonobese subjects. Baseline insulin levels were elevated significantly in the obese (20 +/- 3 microU/mL) compared with the nonobese (5 +/- 0.7 microU/mL) subjects. Furthermore, insulin levels remained significantly elevated in the obese subjects compared with the nonobese subjects throughout the glucose tolerance test (118 +/- 19 vs 49 +/- 6 microU/mL, obese vs nonobese subjects at 1-hour post-glucose tolerance test).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1518706 TI - Screening for fungal endophthalmitis in children at risk. AB - To evaluate the efficacy of screening ophthalmologic examinations in high-risk children, we reviewed the medical records for all patients hospitalized from 1985 through 1989 at The Hospital for Sick Children, Toronto, Ontario, who underwent ophthalmological consultation to rule out endogenous fungal endophthalmitis (n = 176). The patients were divided into groups: Group 1 (n = 47), those with deep tissue fungal infection, and Group 2 (n = 129), those at risk for invasive fungal disease. Group 2 was subdivided further into two subgroups: Group 2a (n = 48), those with evidence of superficial fungal colonization (positive fungal culture) but no deep-tissue involvement, and Group 2b (n = 81), those with no evidence of fungal colonization (negative fungal culture). Of these 176 patients, 7 were diagnosed with endogenous fungal endophthalmitis: 6 from Group 1, 1 from Group 2a, and 0 from Group 2b. We found a significant association between the development of endogenous fungal endophthalmitis and the status of the fungal culture result (P less than .005). The odds ratio indicated the risk of endogenous fungal endophthalmitis in Group 1 patients with deep-tissue infection was at least 19 times that of Group 2 at-risk patients. The risk of endogenous fungal endophthalmitis in Group 1 patients was at least 7 times that of Group 2a colonized patients and 12 times that of Group 2b patients with no positive fungal culture. Our study confirms the necessity of careful dilated ophthalmoscopic examination in patients with invasive fungal disease and suggests screening for those at-risk patients with superficial fungal colonization.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1518707 TI - Nickel allergy from a bed-wetting alarm confused with herpes genitalis and child abuse. PMID- 1518708 TI - Smooth muscle tumors in children with human immunodeficiency virus infection. PMID- 1518709 TI - Safety of an amino acid-derived infant formula in children allergic to cow milk. PMID- 1518710 TI - Neonatal genital prolapse. PMID- 1518711 TI - Elevated cord human chorionic gonadotropin in leprechaunism. PMID- 1518712 TI - American Academy of Pediatrics Committee on Nutrition: Statement on cholesterol. PMID- 1518713 TI - Meconium and tracheal aspiration. PMID- 1518714 TI - Meconium and tracheal aspiration. PMID- 1518715 TI - Meconium and tracheal aspiration. PMID- 1518716 TI - Meconium aspiration pneumonitis and/or persistent fetal circulation. PMID- 1518717 TI - Meconium aspiration syndrome (MAS) PMID- 1518718 TI - FDA varicella warning. PMID- 1518719 TI - Lead toxicity in the 21st century: will we still be treating it? PMID- 1518720 TI - Estimated number of AIDS orphans in the United States. PMID- 1518721 TI - Basics and recommendations for brain SPECT. Task Group "Neurology" of the European Association of Nuclear Medicine. AB - In this article guidelines for single-photon emission computerized tomography (SPECT) of the brain are presented by the Task Group "Neurology" of the European Association of Nuclear Medicine (EANM). Under separate headings are discussed: the pathophysiologic principles of various brain diseases, pharmacokinetics and pharmacodynamics of various radiopharmaceuticals, physical principles of SPECT imaging, computerized data processing, clinical protocols and the evaluation of SPECT results. PMID- 1518722 TI - [Is a TSH screening for the diagnosis or exclusion of functional thyroid autonomy meaningful?]. AB - A normal baseline TSH serum concentration is accepted as excluding thyroid dysfunction. The present study examined the usefulness of that concentration as a screening test for functional autonomy. 310 patients were retrospectively examined. They were all clinically euthyroid and had normal peripheral thyroid hormone concentrations. The positive predictive value for the confirmation of autonomy was 55.5%, the negative predictive value for the exclusion of autonomy 87.7%, using 0.5 mU/l as a lower limit. The probability for the presence of thyroid autonomy in patients with a TSH serum concentration below 0.3 mU/l was 72.5%. PMID- 1518723 TI - Late cervical lymph node recurrence in differentiated thyroid carcinoma. An inherent problem of 131I beta dose distribution in small tumor deposits? AB - In differentiated thyroid carcinoma, postoperative radioiodine therapy is an undisputed element of the integral therapeutic concept. Sometimes, however, and years after initial diagnosis and therapy, cervical lymph node metastases occur without any evidence of local relapse or distant metastases, indicating that radioiodine therapy has not achieved definite tumor cell sterilization. A Monte Carlo computer simulation of the spatial energy dose distribution of 131I in small functioning tumor manifestations was performed to explain this phenomenon. It appeared that only a small fraction of the total beta-energy dose can be deposited inside the tumor if the latter becomes smaller than 1 mm in diameter: for tumors with homogeneous 131I uptake and diameters of 1.0, 0.5, 0.2, 0.1, 0.05 and 0.02 mm, this value does not exceed 86, 73, 39, 16, 8 and 4%, respectively. These data suggest a potential therapeutic gap for small tumor manifestations not apparent at the time of initial diagnosis and could explain the occasional occurrence of late cervical lymph node metastases. PMID- 1518724 TI - [Radioiodine therapy of differentiated thyroid cancer. Recommendations of the Therapy Study Group of the German Society of Nuclear Medicine]. PMID- 1518725 TI - Ode to beer cans, canoes, house trailers, and Jimmy Buffet. PMID- 1518726 TI - Variability in teniposide plasma protein binding is correlated with serum albumin concentrations. AB - Teniposide is a widely used anticancer drug that is extensively bound to plasma proteins (greater than 95%). We evaluated the drug's plasma protein binding in nine patients with acute lymphocytic leukemia who were in their first complete remission, and in a second group of nine patients at the time of relapse and subsequently after achieving another complete remission. Plasma protein binding was assessed by equilibrium dialysis, with direct high-performance liquid chromatographic measurement of total and free teniposide. The mean unbound fraction was 0.44% (0.21-0.88%) in the plasma of patients in first remission. It was significantly higher in patients at the time of relapse (mean = 0.86%; range 0.68-1.08%) and after achieving another complete remission (mean = 1.25%; range 0.51-2.11%). Serum albumin values were significantly lower at the time of relapse (mean = 4.6 vs 4.0 mg/dl; p less than 0.014), and decreased further during intensive postremission therapy containing L-asparaginase (mean = 3.2; p less than 0.05). For all 18 patients, a significant negative correlation (r2 = 0.667; p less than 0.001) was found between serum albumin and unbound teniposide, with low albumin being associated with higher unbound fraction. Such patients have higher systemic exposure to unbound (presumably active) teniposide at any given total plasma concentration of the agent. PMID- 1518727 TI - Prospective evaluation of risk factors for antibiotic-associated bleeding in critically ill patients. AB - A prospective surveillance program was initiated to determine the relative role of antibiotics containing N-methylthiotetrazole (NMTT) versus patient risk factors in producing antibiotic-associated bleeding. Five hundred forty-six critically ill patients with serum albumin 30 g/L or below were evaluated for evidence of a bleeding event as documented by clinical observation, hemoglobin changes, and transfusions. Bleeding events occurred in 16% of patients receiving an aminoglycoside combination, 10% receiving antibiotics with the NMTT side chain, and 14.5% receiving antibiotics not containing NMTT (p greater than 0.05). The bleeding rate was highest in febrile patients with cancer (14.5%) and lowest in those with a suspected or documented abdominal infection (10%) (p = 0.04), but within each patient group there was no difference among the antibiotics. We conclude that the use of NMTT-containing antibiotics is not an independent risk factor for bleeding, but the role of severity of illness may be underappreciated. PMID- 1518728 TI - Combination use of sulfonylureas and insulin in the treatment of noninsulin dependent diabetes mellitus. AB - Combination therapy with insulin and sulfonylureas for treatment of noninsulin dependent diabetes mellitus has been evaluated frequently. However, many of the trials either lacked proper control or were of inadequate duration, and none compared combination therapy to intensive insulin therapy using several daily injections. Such a combination decreases, but does not return to normal, glycosylated hemoglobin and fasting glucose concentrations in comparison to therapy with one or two daily injections of insulin in some subjects. Alternatively, adding a sulfonylurea to insulin therapy may allow a reduction in the insulin dosage without compromising glycemic control. When considering the use of the two agents, the possible advantage of a simplified insulin regimen must be weighed against the disadvantages of an increased potential for adverse effects and increased cost. PMID- 1518729 TI - Cerebral blood flow changes with enalapril. AB - Patients with carotid artery occlusive disease (CAOD) may be at increased risk of iatrogenic cerebral hypoperfusion. Using the 133xenon-inhalation technique, we evaluated the effects of enalapril on regional cerebral blood flow (CBF) in 14 patients with chronic hypertension, 7 with CAOD and 7 without CAOD (no CAOD). Regional CBF and blood pressure were measured before and 60 minutes after a single dose of enalapril. Changes in mean arterial pressure after enalapril were not significantly different between the two groups: CAOD -4.67 +/- 8.7 mm Hg, no CAOD -6.18 +/- 8.2 mm Hg. Changes in mean CBF after enalapril were also not statistically different: CAOD -1.0 +/- 3.9, no CAOD 1.0 +/- 2.8. In the CAOD group only, however, changes in CBF were significantly related to increasing age (r = -0.9253, p less than 0.01), such that in patients 65 years or older CBF tended to decrease, whereas in younger patients it increased. Elderly patients with CAOD may be at increased risk of iatrogenic cerebral hypoperfusion, and it may be appropriate to evaluate prospectively the effects of antihypertensive medications on CBF. PMID- 1518730 TI - Theophylline--an alternative therapy for bradyarrhythmia in the elderly. AB - Treating elderly debilitated patients with symptomatic bradyarrhythmia may be difficult. Traditional therapy includes use of limited resources (intensive care unit monitoring) and expensive interventions (permanent pacemaker insertion). When a pacemaker is not ideal or appropriate, yet intervention is desired to improve quality of life, theophylline may be a safe and effective alternative therapy. We expanded this use of theophylline in a series of 11 patients admitted 14 consecutive times with hemodynamically compromising bradyarrhythmias, including atropine-resistant complete heart block with idioventricular rhythm. Three patients experienced deterioration of status and recurrence of bradycardia with the withdrawal or reduction of theophylline, and subsequent recovery of heart rate and conduction with its resumption. PMID- 1518731 TI - Chronic cough responsive to ibuprofen. AB - A 57-year-old woman believed that ibuprofen, prescribed for back pain, improved her idiopathic chronic cough that had been resistant to inhaled and oral corticosteroids. To confirm this observation, we performed an n-of-1 clinical trial with four treatment periods, each separated by a 4-day washout. Ibuprofen 1800 mg/day for 6 days or placebo was randomly allocated in a double-blind fashion with a block size of 4. The number of coughs during the first 30 minutes after awakening were counted daily throughout the study using a tape recorder. Sixty-two coughs/hour occurred while taking ibuprofen, compared with 164 with placebo. We conclude that ibuprofen may be effective in idiopathic chronic cough, and suggest that prostaglandins may be pathogenic factors in some patients. PMID- 1518733 TI - Quality of life measurements in oncology. AB - Quality of life (QOL) has transcended from an implicit concern to an explicit measurement in oncology. In contemporary clinical research, QOL can now often be identified and objectively measured in health as well as in illness. The major domains which comprise QOL in patients with cancer include symptoms and side effects, social function, physical function, and psychological status. One of the preferred methods for measuring QOL consists of self-administered questionnaires. A number of instruments have been developed which vary in features such as type of domains included, number of items, response options, specificity for disease type, and psychometric assessments. The role of QOL assessment is becoming increasingly important in clinical oncology. PMID- 1518732 TI - Increase in serum digoxin concentrations after indomethacin therapy in a full term neonate. AB - Digoxin was administered to an 18-day-old infant who showed evidence of cardiac failure. When a Doppler echogram revealed a patent ductus, indomethacin was administered for medical management. Therapeutic digoxin doses then resulted in toxic serum concentrations of 8.2 ng/ml. Serum creatinine rose accordingly. Although this patient did not manifest signs of digoxin toxicity, practitioners should be alerted to the potential complications of these commonly used agents. PMID- 1518734 TI - Parenteral nutrition support in patients with cancer. AB - In the patient with cancer, malnutrition may result from the disease itself or from its treatment. Total parenteral nutrition (TPN) has been used for many years to treat or prevent malnutrition in the patient with cancer. There have been few studies, however, that demonstrate significant benefit from TPN therapy in these patients. Patients receiving high-dose chemotherapy (as in bone marrow transplantation), and patients with solid tumors who have documented malnutrition (cachexia, weight loss) prior to cancer surgery, may benefit from TPN. No other groups of patients with cancer appear to derive significant benefit from TPN, and some groups may actually be harmed by its use. Practical considerations in the use of TPN include periodic calorie-protein assessment, electrolyte management, and monitoring for drug-TPN interactions. PMID- 1518735 TI - Clinical pharmacy practice in the noninstitutional setting. A white paper from the American College of Clinical Pharmacy. The ACCP Clinical Practice Affairs Committee, 1990-1991. PMID- 1518736 TI - Natural and modified history of isolated ventricular septal defect: a 17-year study. AB - We studied 882 cases of isolated ventricular septal defect (VSD) diagnosed from 1971 to 1988 with a mean follow-up period of 9.5 years. They represent 22.5% of all congenital heart defects diagnosed in this period. Six hundred eighty-three children (77.4%) did not develop symptoms, had small defects, and the rate of spontaneous closure was high (40.2%). The remaining 199 children presented symptoms; at the initial catheterization 25, 65, 107, and 2 cases were grouped in hemodynamic groups 2, 3, 4, and 5-6, respectively, on the basis of pulmonary flow and resistance. Only seven patients (0.7%) developed aortic regurgitation, and only five patients (0.5%) developed infective endocarditis. Complete surgical correction was performed in 137 children (15.5% of the total cases), with surgical mortality decreasing from 21.4% before 1983 to 3.5% afterward. Overall mortality was 3% for the entire cohort, 0% for hemodynamic groups 1 and 2, 3% for group 3, and 25% for hemodynamic groups 4-6. About two thirds of the deaths took place between 1 month and 1 year of life, and one thirds of the deaths occurred before surgical treatment. Surgical mortality rates for hemodynamic groups 2, 3, and 4 were 0, 4.7, and 15.3%, respectively. Actuarial survival curves show an important improvement in the prognosis after 1983. Our results stress the importance of early surgical complete correction on patients with large defects and severe hemodynamic changes. PMID- 1518737 TI - Bacterial endocarditis in children: trends in its diagnosis, course, and prognosis. AB - In a population-based study of 41 children with bacterial endocarditis (BE), diagnosed in the period 1970 through 1989 in eastern Denmark, we analyzed trends in the diagnosis of BE and in mortality, and searched for possible prognostic factors. During this period the delay in diagnosis from first symptom to treatment did not change, but the delay from admission to treatment was significantly prolonged from 0 to 3 days, despite the introduction of echocardiography (ECHO). There was a significant improvement in the prognosis, the mortality rate having decreased from 40 to 0% [95% confidence limits: 12-74 vs. 0-26 (0.01 less than p less than 0.02)]. The improved prognosis was not explained by changes in the etiology or pattern of antibiotic resistance and may reflect a milder course of BE in children. Children with "mild anomalies"--such as bicuspid aortic valve (n = 5), coarctation of the aorta (n = 2), and prolapse of the mitral valve (n = 2)--had a significantly poorer prognosis than children with other forms of congenital heart disease (CHD) (p = 0.004), a reminder of the importance of suspecting BE in all children with unexplained long-lasting or intermittent fever, because some may have unrecognized "mild" CHD. PMID- 1518738 TI - HLA and rheumatic fever in Turkish Children. AB - We report the results of research on human leukocyte allo-antigen (HLA) and rheumatic fever (RF), the first published study to be carried out among Turkish children with RF. Ninety-three Turkish children, aged between 6 and 16 years (mean: 8 +/- 2.6), with RF participated in the study. Of the total, 26 patients had their first attack and 39 had acute rheumatic activity at the time of registration. The results demonstrate (1) negative but not significant association between HLA-A2 and RF; (2) a positive association between HLA-DR4 and RF (p less than 0.001); (3) a significant association between HLA-DR4 and carditis, but not with isolated arthritis. These results corroborate the concept of race-specific genetically determined familial susceptibility to the development of rheumatic heart disease. PMID- 1518739 TI - Acute renal failure complicating pediatric cardiac surgery: a comparison of survivors and nonsurvivors following acute peritoneal dialysis. AB - The outlook for patients with cardiac surgery complicated by acute renal failure (ARF) is poor, with a reported mortality of 50-67%. In addition to assessing the impact of recent advances in pediatric cardiac surgery on the mortality rate and renal outcome of surgery complicated by ARF requiring peritoneal dialysis (PD), this study compares preoperative, operative, and postoperative variables in patients who survived surgery and those who did not survive. From 1982 through 1988, 44 postoperative cardiac patients developed ARF, and 40 (age: 2 days to 15 years) required PD. Seventeen of 40 patients survived (mortality 57.5%) and 16 of these patients recovered normal renal function. Preoperative variables, including operative age and weight, did not appear to directly influence survival. Operative profiles, including length of cardiopulmonary bypass, aortic cross clamp time, and hypotension immediately off bypass, did not distinguish surviving patients from those that did not survive. Postoperative variables, such as postoperative hypotension treatment, arrhythmias, hematologic status, cardiac arrest with resuscitation, did not differentiate survivors from nonsurvivors. The mean duration of PD was less than 2 weeks, and complications were infrequent. Renal status following PD in survivors was usually normal. We conclude that recent advances in pediatric cardiac surgery have not further increased the high mortality of surgery complicated by ARF. Survival is associated with renal recovery and thus aggressive treatment using PD is warranted. PMID- 1518740 TI - Interrupted aortic arch in infancy: a 10-year experience. AB - Fifty infants with interrupted aortic arch (IAA), admitted between 1979 and 1988, were reviewed. They usually presented early in severe cardiac failure or shock. In the initial 5-year period, 17 of the 21 infants underwent diagnostic or confirmatory cardiac catheterization, in contrast with the latter 5 years when only eight of the subsequent 29 patients underwent catheterization. Since 1987, all patients underwent surgery after cross-sectional echocardiography. Fifteen infants had a type A IAA and 35 had type B. All had associated cardiac anomalies. Four infants were not operated on. In the initial 5-year period, of 17 infants who were surgically treated, four had a one-stage total repair, the remaining had a two-stage repair with initial reconstruction of the arch and pulmonary artery banding. There was an overall surgical mortality of 65%, reflecting the precarious state of many of these infants before surgery with a significant contribution from unrelieved subaortic stenosis. In the latter 5-year period, 29 underwent surgery, 22 had a one-stage total repair. There were three deaths, all in infants whose active treatment was withdrawn. The outcome of the survivors has generally been good, subsequent surgery being mainly related to the associated anomalies (e.g., recurrent subaortic stenosis, conduit replacement). Over this 10 year period the greater accuracy of noninvasive diagnoses, and perioperative intensive care, have led to an improvement in the preoperative state of these infants. Single-stage total repair is our procedure of choice. PMID- 1518741 TI - Aneurysm of the ductus arteriosus in the neonate: three case reports with a review of the literature. AB - Ductus arteriosus aneurysm was demonstrated in three neonates by echocardiography. One case was already diagnosed in utero. One patient needed surgical resection, whereas in one case the aneurysm of the ductus arteriosus regressed spontaneously. In the third case the patient died of associated lesions. In a review of the literature, 61 previous cases of ductus aneurysm in infants less than 2 months were found. Ductus arteriosus aneurysm may be diagnosed by echocardiography both pre- and postnatally. A ductus aneurysm should be monitored closely by echocardiography. Since a high incidence of complications is reported, surgical resection is indicated if the aneurysm does not regress within a few days. PMID- 1518742 TI - Amiodarone therapy of intractable atrial flutter in a premature hydropic neonate. PMID- 1518743 TI - Endocarditis with acute mitral regurgitation caused by Fusobacterium necrophorum. AB - Infective endocarditis is uncommon in young children, especially in the absence of structural heart disease. We report the case of a 2-year-old boy who presented with acute rupture of the mitral valve chordae 6 weeks after an episode of Fusobacterium necrophorum septicemia. His heart had been structurally normal before. Mitral valve replacement was successfully performed. This is the first recorded case of endocarditis in a child caused by necrobacillosis. PMID- 1518744 TI - Necrotizing arteritis in uncorrected tetralogy of Fallot with pulmonary artery. AB - A 10-year-old girl with uncorrected tetralogy of Fallot with pulmonary atresia presented with fevers of unknown origin and left lung infiltrates. At autopsy, necrotizing vascular changes resembling those of severe pulmonary hypertension (grade VI in the Health-Edwards classification) were confined to the left lung. Pulmonary blood flow and pressure were greater in the left lung and were provided by an enlarged collateral artery arising directly from the descending thoracic aorta. To our knowledge, this is the first report of necrotizing arteritis of the pulmonary arteries in uncorrected tetralogy of Fallot with pulmonary atresia. PMID- 1518745 TI - Intracardiac calcifications in a case of pseudohypoparathyroidism type Ia (PHP Ia). AB - In a 10-year-old boy with pseudohypoparathyroidism type Ia (PHP-Ia) echocardiography detected calcifications within the ventricular septum. This is thought to be the first report of intracardiac calcifications in PHP. Echocardiography should be done routinely in all patients with this rare disorder. PMID- 1518746 TI - Inferior vena cava thrombus in infants. PMID- 1518747 TI - Heart failure secondary to hypomagnesemia in anorexia nervosa. PMID- 1518748 TI - Occupational asthma. 'My job is making me sick!'. AB - Future well-organized epidemiologic studies may enhance our understanding of the risk factors, prognosis, and natural course of asthma caused by a variety of inciting agents found in the workplace. Until such studies are completed, employees should be educated regarding exposure to hazardous chemicals, and strict safety measures should be enforced to prevent large spills of chemicals and other unnecessary risks. PMID- 1518750 TI - Resurgence of rheumatic fever in the United States. The changing picture of a preventable illness. AB - The recent resurgence of rheumatic fever reported in eight locations in the United States after years of decline has several noteworthy characteristics. Most patients were children of families in high- to middle-income brackets with ready access to medical care. In four of the outbreaks, the majority of patients were adults, who were more likely than children to have arthritis and less likely to have Sydenham's chorea. Many patients had no clinical history of streptococcal pharyngitis. Rheumatic fever developed in some patients despite antibiotic treatment for streptococcal pharyngitis. Analysis of the outbreaks supports the following conclusions: No population is exempt from rheumatic fever. Physicians should be diligent in performing throat cultures in cases of suspected streptococcal pharyngitis. The efficacy of orally administered penicillin in preventing rheumatic fever should be reexamined, and oral antibiotics that are potentially more effective should be sought. PMID- 1518749 TI - Anticoagulant therapy for atrial fibrillation. Recommendations from major studies. AB - The role of antithrombotic therapy in reducing thromboembolic complications in patients with chronic atrial fibrillation has been clarified by the results of four major randomized and placebo-controlled trials. Patients with rheumatic heart disease complicated by atrial fibrillation should receive long-term warfarin therapy to reduce the risk of stroke unless an absolute contraindication exists. Patients with nonrheumatic atrial fibrillation should also be treated with low-dose warfarin therapy, especially if high-risk features for thromboembolism exist. In patients who have contraindications to warfarin therapy and in young patients with lone atrial fibrillation or paroxysmal atrial fibrillation, therapy with 325 mg of aspirin a day is preferred. Ongoing trials directly comparing aspirin and warfarin will provide additional insight into the optimal role of these antithrombotic agents in patients with atrial fibrillation. PMID- 1518751 TI - Depression in physically ill patients. Don't dismiss it as 'understandable'. AB - Depression in the physically ill is common and may even be caused by certain physical disorders (eg, hypothyroidism, pancreatic cancer) or the use of some types of drugs. It should not be dismissed because it is "understandable" in particular situations, but rather, it should be differentiated from overlapping symptoms of the physical disorder and treated. The effect of psychosocial factors should be carefully considered. PMID- 1518752 TI - Prophylaxis for malaria. Helping world travelers come home healthy. AB - Malaria is largely preventable, so travelers should be taught general protective measures and given appropriate chemoprophylaxis before they leave on their trip. Chloroquine phosphate (Aralen) is still the drug of choice in locations where malaria remains chloroquine-sensitive. However, chloroquine-resistant areas infested with Plasmodium falciparum are becoming more numerous. In such areas, mefloquine hydrochloride (Lariam), doxycycline, or proguanil (Paludrine) (obtainable outside the United States) may be used. A single dose of pyrimethamine-sulfadoxine (Fansidar) may be used to treat presumptive malarial infection if medical care is not immediately available. For prevention of relapse of Plasmodium vivax and Plasmodium ovale infection, primaquine phosphate is recommended for the final 2 weeks of chemoprophylaxis on return from a malarious area. PMID- 1518753 TI - Preventing postoperative medical complications. How primary care physicians can help. AB - Just as your concern for your patients' welfare does not stop at the operating room door, neither does your opportunity to improve their prognosis. Drs Elnicki and Shockcor believe that primary care physicians have a unique role in total patient care. In this article, they discuss prevention of major postoperative complications and recommend ways primary care physicians can help optimize their patients' perioperative status. PMID- 1518755 TI - The ABZzzzs of snoring. AB - Snorers sleep through their obnoxiously loud breathing, but other members of their household often do not. Their bed partner and family members may grow so tired of the noise that they insist the offender seek medical attention. Physiologic problems such as obesity, narrowing of the airway, or inadequate oropharyngeal muscle tone often can be identified as the cause of snoring. Whenever possible, the underlying disorder should be treated. PMID- 1518754 TI - Medical complications of substance abuse. AB - Substance abuse is involved in many instances of intentional and unintentional injury. It can also cause medical complications that affect various organ systems -among them, the cardiac, vascular, neurologic, pulmonary, gastrointestinal, immunologic, and reproductive systems. Even though there is pressure to create a new medical specialty to specifically address substance-abuse issues, the truth is that any physician, regardless of specialty, may encounter patients with substance-abuse problems. Alcoholism and drug abuse, with their associated psychosocial and clinical ramifications and complications, cut across all specialty fields. Consequently, all physicians need to be familiar with the spectrum of clinical problems associated with substance abuse and comfortable with addressing these problems prudently and promptly. PMID- 1518756 TI - Common thyroid disorders in the elderly. AB - Thyroid disease in the elderly is common but often has an insidious onset with symptoms that mimic those of normal aging. Understanding the significance of thyroid function test results requires an appreciation of the normal physiologic variations of aging and the complicating effects of diseases and medications; only then can one accurately discriminate between various disease processes, order additional appropriate tests, and deliver rational management. The increasing prevalence of thyroid disorders with age, coupled with the current and future dramatic growth of the elderly population, demands that primary care providers be vigilant to the likelihood of thyroid disease and informed as to its most proper, expedient, and cost-effective diagnosis and management. PMID- 1518757 TI - The role of barium enema in detecting colorectal disease. A radiologist's perspective. AB - The single-contrast barium enema examination remains useful for patients with acute diseases such as bowel obstruction, diverticulitis, appendicitis, and fistulas. It is also the procedure of choice for those patients who are too elderly, debilitated, or ill to cooperate with the maneuvers necessary for a double-contrast examination. The double-contrast technique is more sensitive than the single-contrast technique for detection of polyps, early inflammatory bowel disease, and lesions of the rectum. In the older population, there has been an increase in the incidence of colonic polyps and carcinomas in the right side of the colon. This emphasizes the need to examine the entire colon in these patients. The double-contrast barium enema is a safe, accurate, and cost effective tool for accomplishing this. It is also recommended as the initial procedure in the examination of patients with positive results on fecal occult blood testing. PMID- 1518758 TI - Autologous transfusion. A safe alternative for the 1990s. AB - Autologous transfusion is a safe and affordable alternative to the traditional use of homologous blood. Many persons who would not ordinarily meet the criteria for homologous or directed donation can be autologous donors. The use of autologous blood ensures that the patient will not contract AIDS or hepatitis from transfused blood products. Many community hospitals have autologous blood programs, which allow them to draw, store, and reinfuse blood all under one roof. PMID- 1518759 TI - Who was the phantom accuser of 15 doctors? PMID- 1518760 TI - Government regulation of healthcare. PMID- 1518761 TI - Government regulation of healthcare. PMID- 1518762 TI - Government regulation of healthcare. PMID- 1518763 TI - A diagnostic approach to 'difficult' asthma. AB - When patients with asthma do not respond adequately to standard treatment, they are said to have "difficult" asthma. These patients require a lot of healthcare resources, are usually receiving long-term oral corticosteroid therapy, and are significantly sicker than other asthma patients, with attendant increases in morbidity and mortality. In these patients, the management areas summarized in table 1 should be fully explored to determine whether asthma is the correct diagnosis and whether the best care is being given. PMID- 1518764 TI - Correct use of metered-dose inhalers and spacer devices. AB - In addition to prescribing an appropriate drug regimen, physicians must carefully educate asthmatic patients. For 10 million such patients in the United States as well as millions more around the world, successful education is critical to quality of life and can save lives. Responsible patients who understand that asthma attacks are preventable and who use their medications correctly usually have a gratifying response to treatment. Of special importance is the optimal use of aerosolized drugs, most often given by a metered-dose inhaler plus spacer device. PMID- 1518765 TI - Pharmacology and clinical use of a new group of antiarrhythmic drugs: derivatives of tricyclic nitrogen-containing systems. AB - This paper is concerned with a new group of antiarrhythmic drugs: derivatives of phenothiazine and dibenzazepine which belong to tricyclic nitrogen-containing systems. It has been discovered that the transition from omega-aminoalkyl to omega-aminoacyl phenothiazine derivatives results in a decrease in psychotropic activity and an increase in cardiovascular, particularly antiarrhythmic, action. Based on structural and antiarrhythmic activity studies, the new and effective drugs ethmozine, ethacizine and bonnecor have been selected and extensively studied. Data on spectra and mechanisms of their action, obtained in different arrhythmia models, have been confirmed by clinical studies. Correlation between pharmacological properties and electrophysiological mechanisms, and differences in action of the drugs studied on brain and heart plasma membrane receptors may serve as a starting point for the further directed search for new antiarrhythmic drugs among tricyclic nitrogen-containing structures. PMID- 1518766 TI - Does adenosine malfunction play a role in hypertension? PMID- 1518767 TI - Effects of slow release bezafibrate on the lipid pattern and on blood glucose of type 2 diabetic patients with hyperlipidaemia. AB - Ninety-eight type 2 diabetic patients with hyperlipidaemia in stable metabolic control with diet alone (41) or diet plus hypoglycaemic agents (57) were divided into two groups: group 1 was put on treatment with slow release bezafibrate 400 mg a day, while group 2 was considered as control. In group 1, after 1 month of bezafibrate, serum triglycerides fell by 47% and cholesterol by 13%. HDL cholesterol showed a non-significant trend toward an increase. Fasting blood glucose significantly decreased by 6%, fructosamine and glycated haemoglobin by 5%. During OGTT, the area under the curve of both serum C-peptide and blood glucose showed a trend toward a decrease after bezafibrate. However, the difference did not reach statistical significance. Thirty-six patients continued the treatment with the drug for 4 months and 23 for 8 months, without further changes of the lipid pattern and glycaemic control. In the control group no significant variation of the lipid levels occurred and diabetic control slightly worsened during the study. Bezafibrate has been proved to be effective in the treatment of hyperlipidaemia in type 2 diabetic patients. The drug seems moreover to improve glycaemic control. The mechanism by which bezafibrate produces this latter effect remains to be elucidated, though an increase of peripheral insulin sensitivity might be suggested. PMID- 1518768 TI - Effect of furazolidone on tissue sulphydryl groups, ascorbic acid, and lipid peroxide levels in the rat, and the influence of dimethylsulphoxide thereon. AB - The concentrations of sulphydryl groups (SH), ascorbic acid (AA) and lipid peroxide (LP) were measured in the liver, kidney and brain of rats 24 h after treatment with furazolidone at single oral doses of 75, 150 and 300 mg/kg. The drug produced significant reductions in the concentrations of SH, and significant increases in the concentrations of LP, in the tissues studied. The level of AA was significantly decreased in the livers (but not the kidneys or brains) of rats treated with furazolidone at a dose of 300 mg/kg. The concentrations of AA in the tissues of rats treated with lower doses were unaffected. In another experiment, furazolidone was given orally to rats at a dose of 300 mg/kg, together with a subcutaneous injection of dimethylsulphoxide (DMSO) at a dose of 8 g/kg, and SH measured in the liver 24 h later. DMSO alone had no significant effect on SH concentration. However, when DMSO was given concomitantly with furazolidone, SH concentration was significantly less depressed than when furazolidone was given alone. It is concluded that DMSO protected tissues against toxicity induced by furazolidone. PMID- 1518769 TI - Reduced L-arginine/lysine and L-arginine/aspartic acid ratios in aorta from Watanabe heritable hyperlipidaemic (WHHL) rabbit. AB - L-Arginine is the endogenous source of nitric oxide in the endothelial cells of blood vessels. In thoracic aorta from Watanabe heritable hyperlipidaemic (WHHL) rabbits, the L-arginine/lysine and L-arginine/aspartic acid ratios were reduced in comparison to New Zealand rabbit aorta. This result indicates that a variation in aortic arginine/lysine or arginine/aspartic acid ratios could be related to the hyperlipidaemic status. PMID- 1518770 TI - Hypolipidaemic activity in rodents of boron analogs of phosphonoacetates and cyanoborane adducts of dialkyl aminomethylphosphonates. AB - Boron analogues of phosphonoacetates proved to be potent hypolipidaemic agents in rodents, lowering both serum cholesterol and triglyceride levels. (C2H5O)3PBH2COOCH3 proved to be the most effective agent in mice, lowering serum cholesterol 46% and serum triglycerides 54% after 16 days. (C2H5O)3PBH2COOH and Na+H+(C2H5O)2(-O)PBH2COO- caused greater than a 40% reduction in lipids. The cyanoborane adducts of aminomethylphosphonates were generally less effective; (C6H5O)2P(O)CH2NH2BH2CN was the most effective, lowering serum cholesterol 32% and serum triglycerides 43% after 16 days. The phosphonoacetates appeared to lower lipid concentrations by several mechanisms. First, they lowered the de novo synthesis of cholesterol and triglycerides in the liver. Second, they accelerated the excretion of lipids into the bile and faeces. Thirdly, they modulated LDL and HDL-cholesterol contents in a manner which suggests they reduced the deposition of lipids in peripheral tissues, and accelerated the movement of cholesterol from tissues (e.g. plaques) to the liver for excretion into the bile. PMID- 1518771 TI - Inhibition of aromatic amino acid decarboxylase by a group of non-steroidal anti inflammatory drugs. AB - In vitro inhibition of aromatic amino acid decarboxylase (AAD) by eight nonsteroidal anti-inflammatory drugs (NSAIDs) was studied. The most potent inhibitors were fenamates (IC50 for tolfenamate was 4.4 x 10(-5) M), while fluorinated biphenylic compounds (flobufen and 2',4'-difluorobiphenyl-4-yl acetate) and propionic acid derivatives (ibuprofen, ketoprofen, fenoprofen) were one order weaker. The in vitro inhibition of AAD by the compounds studied is probably not strong enough to contribute to their in vivo anti-inflammatory effects. PMID- 1518772 TI - Influence of indomethacin on histamine- and acetylcholine-induced responses in the intact and denuded epithelium of guinea pig tracheal smooth muscle. AB - We have investigated the effect of indomethacin on histamine- and acetylcholine (ACh)-induced responses in the intact and denuded epithelium of guinea pig isolated tracheal smooth muscle. Epithelium removal resulted in increased responsiveness to ACh and histamine. Indomethacin (2.8 microM) enhanced the sensitivity of both intact and denuded preparations to histamine and ACh. These findings suggest that the tracheal epithelium of guinea pig plays a protective role against bronchoconstrictors, such as ACh and histamine. Furthermore, indomethacin-mediated hyperresponsiveness caused by these agonists in epithelium denuded preparations might be a reflection of removal of prostaglandin (PG) biosynthesis. A similar process of interaction in indomethacin-treated asthmatic patients (with damaged airway epithelium) might take place. The significance of these findings is discussed. PMID- 1518773 TI - Field potential analysis in the freely moving rat during the action of cyclandelate or flunarizine. AB - Cyclandelate and flunarizine, two vasoactive Ca2+ channel or Ca2+ overload blockers have been compared with respect to their in vivo action on field potentials recorded from the depths of the brain in freely moving rats. Whereas cyclandelate showed a dose dependent rapid onset of action in the range of 15 to 120 mg/kg i.p., flunarizine only induced weak effects very slowly, not reaching statistical relevance before the fourth hour after the injection (0.1 to 1.6 mg/kg). Even then no clear dose dependence could be recognized for flunarizine. With respect to the frequency content of the recorded signals a rather close similarity between both drugs could be seen. Comparison of the drug effects to our reference data base of more than 80 compounds revealed a close relationship to memantine, an antiparkinson drug, suspected to act on the NMDA (N-methyl-d aspartate) receptor-ionophor complex controlling Ca2+ fluxes. There is some indication that cyclandelate might also act in a similar way at the molecular level. PMID- 1518774 TI - [The beginnings of child analysis]. AB - The notions hitherto existing of the beginnings of child analysis have to be rectified. The meaning of childhood neuroses within the scope of scientific theory, i.e. the sexual genesis of the neuroses can no longer be maintained. The approach of distinguishing between the latent period and the Oedipus complex as the two phases of sexual development can nowadays be considered to be refuted. The personality of the first children's analyst--Hermine Hug-Hellmuth--needs to be redescribed. She fell victim to her father-transference and deceased murdered by her nephew with the help of whom she had satisfied her own scientific ambitions. PMID- 1518775 TI - [Problems in diagnosis of borderline disorders in childhood]. AB - While, for adults, there exists an instrument for diagnosing borderline-disorders (DSM-III-R, ICD 10), this is not the case for children and adolescents. Several attempts of classifying borderline-disorders are discussed (Bemporad et al., Pine, Vela et al.). Exemplified by a case study of the treatment of a ten-year old borderline girl originally diagnosed as "hysteria", eight criteria are listed and explained that seem relevant for diagnostic purposes: (1) heredity and affective disorders, (2) diseases and traumata during the first year of life, (3) development in early childhood, (4) character and intensity of anxiety, (5) self destructiveness, (6) defensive mechanisms, (7) object relationships, (8) countertransference. Attention is drawn to a large-scale empirical study in which, by means of an elaborate questionnaire, child psychiatrists and therapists are asked to characterize symptoms, personality traits and aetiological factors of young borderline patients. This will hopefully solve some problems of differential diagnosis discussed in the article. PMID- 1518776 TI - [The importance of the transitional object for the psychological development of the child]. AB - This study addresses the question whether children taken for treatment to a psychiatric hospital for children and adolescents differ from other, not noticeably disturbed children in their use of a transitional object. Parents of mentally disturbed children between six and eight years of age were interviewed about the transitional objects used by their children. The control group was made up of children of corresponding ages from an ordinary nursery school. Based on the extant literature, the concept of "transitional object" is described and defined. Twenty two research hypotheses were formed and subjected to statistical tests. As the main result concerning the research question it emerged that the children suffering from psychiatrical disturbances needed a transitional object mainly in their fourth year of life, but to some extent even in their fifth and sixth year whereas the "healthy" children in the control group without noticeable disturbances used a transitional object mainly in their first and second years. It could be shown with statistical significance that psychiatrically disturbed children had a transitional object at a later age and for a longer period of time than healthy, undisturbed children. PMID- 1518777 TI - [Family pattern with reference to self organization from the psychoanalytic systematic viewpoint]. AB - Families in crisis may develop a variety of dysfunctional patterns of self organisation. They prove consisting of elements as defined by psychoanalysis, family dynamics and systemic-constructivistic thinking. Such patterns are: "Innerfamiliar polarisation" (produced by a family specific "Sprachregelung") the "fight of shadow families", "competition for the same place in the generational net", "transjection" and "magic threshold". Those patterns will be demonstrated by the example of an anorectic family, treated with a psychodynamic concept. The knowledge of these patterns proved to be useful for different kinds of family therapy. Some theoretical questions as analogies from social and physiological (formal) genetics and modalities of transgenerational transmission of family patterns will be discussed shortly. PMID- 1518778 TI - [Gene library of Dunaliella salina, prepared in a cosmid vector of new design]. AB - The gene library (56,160 clones) of the halotolerant alga Dunaliella salina was obtained using a novel cosmid vector pBbv-cosII. The mean size of the insertions is 35-45 kb. Hybridization screening demonstrated that both nuclear and chloroplast DNA-containing clones are presented in the library. PMID- 1518779 TI - Validity of health-related quality of life subscales. AB - This report assesses the validity of subscales from the Quality of Life Index (QLI). Subscale validity is tested across different samples of patients with cancer and other diseases. The results of the factor analyses of different versions of the QLI tested in six studies confirm four important health-related quality of life dimensions. These dimensions are psychological well-being, physical well-being, symptoms/side effects, and nutrition. Psychological well being is represented by a satisfying life, having a good (general) quality of life, having fun, feeling happy and enjoying life. Physical well-being is defined by tiring easily (fatigue), ability to work/carry out usual tasks, strength, and feeling healthy. The symptoms/side effects dimension is characterized by nausea, vomiting, pain distress, and perhaps, by pain amount and pain frequency. Finally, the nutrition dimension is represented by able to eat/eat sufficiently, eating pleasure/appetite, worry about weight, and possibly also taste changes. Good construct validity can be attributed to these health-related quality of life subscales. PMID- 1518780 TI - Conceptualizations of quality of life in cardiovascular research. AB - The purpose of this article is to examine how quality of life has been conceptualized in studies of patients with cardiovascular disorders. To accomplish this purpose the instruments that were used as measures of quality of life in 22 published studies were examined. The majority of conceptualizations could be grouped into five broad categories: social utility, happiness/affect, satisfaction, achievement of personal goals, and normal life. Most of the studies used more than one category to measure quality of life. PMID- 1518781 TI - The integration of health quality of life in clinical research: experiences from cardiovascular clinical trials. AB - Health Quality of Life (HQL) assessment in clinical trial and epidemiological research is necessary to determine the efficacy of treatments and interventions. A definition of HQL is presented with the following dimensions of HQL identified: social, physical, and neuropsychological functioning; emotional stability; personal productivity; and intimacy. A strategy for selecting HQL dimensions and measures is discussed and includes consideration of the study population, the intervention(s), and the clinical trial design. Examples from NHLBI-sponsored clinical trials illustrate how HQL measures are selected as well as the goals that HQL assessment can address. That is, the authors discuss how HQL data can be used to characterize the study populations, determine the effects of HQL on critical outcomes, and assess how treatment affects overall HQL and specific dimensions of HQL. PMID- 1518782 TI - Relative importance of dimensions in the assessment of health-related quality of life for patients with hypertension. AB - There are many different approaches to quality of life measurement. Most of these methods consider several dimensions of health status. However, few of the current methods evaluate the relative importance of the various dimensions. We suggest that the relative importance dimension is of central importance in the development of a general theoretical conceptualization of health outcome. Further, we offer a General Health Policy Model that can be used to evaluate outcomes in cardiovascular care and to compare the cost/utility of cardiovascular interventions to investments in other aspects of health care. Employing the relative importance concept requires several important assumptions and methodological challenges. For example, we must select between competing measurement methodologies and we must decide whose values to use in the models. As new research addresses these questions, we expect greater use of the models in patient decision making and in health policy research. PMID- 1518783 TI - Multidimensional assessment of quality of life in clinical studies. AB - Four types of issues in conducting a multidimensional assessment of quality of life in clinical studies are presented: practical issues, measurement issues, data quality issues, and data analysis issues. The various issues are described, and ways of dealing with the issues are discussed. Examples are used from the literature and also from the author's multivariate, longitudinal study on quality of life in cardiac transplant patients. Consideration of these issues and knowing options for dealing with them before the study is conducted is imperative. With a carefully thought out approach to better planning of the study, the clinician/investigator can conduct a scientifically sound study with credible results that will provide meaningful direction for improving the quality of life of clinical populations in the future. PMID- 1518784 TI - Hydrophobicity and structural classes in proteins. AB - The bulk hydrophobic character for the 20 natural amino acid residues, has been obtained from a database of 60 protein structures, grouped in the four structural classes alpha alpha, beta beta, alpha + beta and alpha/beta. The hydrophobicity coefficients thus obtained are compared with Ponnuswamy's original values using scales normalized to average = 0.0 and standard deviation = 1.0. Even though most of the amino acid residues do not change their hydropathic character in the different structural classes, their behaviour suggests the convenience that averaging methods should only consider proteins of the same structural class and that this information should be included in the secondary structure methods. PMID- 1518785 TI - IPSA-Inductive Protein Structure Analysis. AB - The Inductive Structure Protein Analysis (IPSA) project presents a new method for investigating protein structure. IPSA includes the creation of a new database which was designed specifically for the analysis of protein structure by statistics and machine learning. The Protein Representation Language (PRL) database includes explicit and symbolic representations of geometrical, topological and chemophysical information about secondary structures and the relationships between secondary structures. The IPSA methodology consists of: the use of PRL information to produce a new database of examples of secondary structures which associate together (examples of possible super-secondary structures); then the use of a variety of clustering techniques to produce a consensus clustering of these examples (super-secondary structures); these super secondary structures are finally examined to uncover any biological features of significance. We have applied this method to find simple super-secondary structures consisting of pairs of alpha-helices. We found four well-defined super secondary structures, one formed exclusively by long range interactions, and another in association with an additional element of secondary structure (alpha t alpha-motif). Examinations were carried out using homologous pairs and conformational fits which confirm our clustering. PMID- 1518786 TI - Molecular modeling studies in the complex between cyclophilin and cyclosporin A. AB - The structure of the complex between cyclophilin and cyclosporin A is predicted by combining X-ray crystallographic and NMR spectroscopic data using molecular modeling. The drug was placed at the receptor site using a directed docking procedure in which an impulse is imparted to a pre-oriented ligand along an established path. Both ligand and receptor atoms are flexible during the procedure. Two conformers of the MeBMT side chain are shown to result in similar ligand-receptor interaction energies. The models for the drug-receptor complex appear consistent with known experimental data and provide a significant opportunity for the design of compounds with enhanced therapeutic value. PMID- 1518787 TI - Additional binding sites in lysozyme. X-ray analysis of lysozyme complexes with bromophenol red and bromophenol blue. AB - The binding sites in hen egg-white lysozyme for neutral bromophenol red (BPR) and ionized bromophenol blue (BPB) have been characterized at 2 A resolution. In either case, the dye-bound enzyme is active against the polysaccharide, but not against the cell wall. Both binding sites are outside, but close to, the hexasaccharide binding cleft in the enzyme. The binding site of BPR made up of Arg5, Lys33, Phe34, Asn37, Phe38, Ala122, Trp123 and possibly Arg125, is close to subsite F while that of BPB made up of Tyr20, Arg21, Asn93, Lys96, Lys97 and Ser100, is close to subsites A and B. The binding sites of the neutral dye and the ionized dye are thus spatially far apart. The peptide component of the bacterial cell wall probably interacts with these cells during enzyme action. Such interactions are perhaps necessary for appropriately positioning the enzyme molecule on the bacterial cell wall. PMID- 1518788 TI - Crystal structure of the high-alkaline serine protease PB92 from Bacillus alcalophilus. AB - The crystal structure of a serine protease from the alkalophilic strain Bacillus alcalophilus PB92 has been determined by X-ray diffraction at 1.75 A resolution. The structure has been solved by molecular replacement using the atomic model of subtilisin Carlsberg. The model of the PB92 protease has been refined to an R factor of 14.0% and contains 1882 protein atoms, two calcium ions and 188 water molecules. The overall folding of the polypeptide chain closely resembles that of the subtilisins. Furthermore, almost all of the secondary structure elements found in subtilisin Carlsberg are also present in the PB92 protease. The major differences between the two structures are located around the deletion regions (residues 37 and 158-161 in subtilisin Carlsberg) and in two loops which are known to be the most variable parts of subtilisin structures. Flexibility of one of these loops (residues 126-130 in the PB92 protease) is believed to account for the induced-fit mechanism of substrate binding. PMID- 1518789 TI - Protein engineering of the high-alkaline serine protease PB92 from Bacillus alcalophilus: functional and structural consequences of mutation at the S4 substrate binding pocket. AB - Serine endoproteases such as trypsins and subtilisins are known to have an extended substrate binding region that interacts with residues P6 to P3' of a substrate. In order to investigate the structural and functional effects of replacing residues at the S4 substrate binding pocket, the serine protease from the alkalophilic Bacillus strain PB92, which shows homology with the subtilisins, was mutated at positions 102 and 126-128. Substitution of Val102 by Trp results in a 12-fold increase in activity towards succinyl-L-Ala-L-Ala-L-Pro-L-Phe-p nitroanilide (sAAPFpNA). An X-ray structure analysis of the V102W mutant shows that the Trp side chain occupies a hydrophobic pocket at the surface of the molecule leaving a narrow crevice for the P4 residue of a substrate. Better binding of sAAPFpNA by the mutant compared with the wild type protein as indicated by the kinetic data might be due to the hydrophobic interaction of Ala P4 of the substrate with the introduced Trp102 side chain. The observed difference in binding of sAAPFpNA by protease PB92 and thermitase, both of which possess a Trp at position 102, is probably related to the amino acid substitutions at positions 105 and 126 (in the protease PB92 numbering). Kinetic data for the variants obtained by random mutation of residues Ser126, Pro127 and Ser128 reveal that the activity towards sAAPFpNA increases when a hydrophobic residue is introduced at position 126.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1518790 TI - The effect of cavity-filling mutations on the thermostability of Bacillus stearothermophilus neutral protease. AB - Cavities in the hydrophobic core of the neutral protease of Bacillus stearothermophilus were analyzed using a three-dimensional model that was inferred from the crystal structure of thermolysin, the highly homologous neutral protease of B. thermoproteolyticus (85% sequence identity). Site-directed mutagenesis was used to fill some of these cavities, thereby improving hydrophobic packing in the protein interior. The mutations had small effects on the thermostability, even after drastic changes, such as Leu284----Trp and Met168 ---Trp. The effects on T50, the temperature at which 50% of the enzyme is irreversibly inactivated in 30 min, ranged from 0.0 to +0.4 degrees C. These results can be explained by assuming that the mutations have positive and negative structural effects of approximately the same magnitude. Alternatively, it could be envisaged that the local unfolding steps, which render the enzyme susceptible towards autolysis and which are rate limiting in the process of thermal inactivation, are only slightly affected by alterations in the hydrophobic core. PMID- 1518791 TI - Permuteins of interleukin 1 beta--a simplified approach for the construction of permutated proteins having new termini. AB - A technique for the rapid and simple generation of permutated versions of the interleukin-1 beta (IL-1 beta) gene is described. In this method, the human IL-1 beta cDNA is twice amplified by the polymerase chain reaction (PCR) and the resulting DNA fragments are ligated in tandem. Between the two genes, the DNA sequence encodes a short four amino acid loop to link the native N- and C terminal ends of the IL-1 beta protein. By using PCR amplification from this starting template, a new version of the IL-1 beta cDNA was obtained that encodes a permutated form of the IL-1 beta protein where the new N- and C-terminal amino acids correspond to residues 65 and 64 of the native IL-1 beta sequence, respectively. The name 'permutein' is proposed to describe proteins generated by this technology. The molecular profile (IL-1 receptor binding, biologic activity and solution properties) of the IL-1 permutein produced by this technology, permutein 65/64, is shown to be identical to that of native IL-1 beta. The approach should be useful to define further the structural features of this protein that are important for its function. PMID- 1518792 TI - Bipartite organization of the Bacillus subtilis endo-beta-1,4-glucanase revealed by C-terminal mutations. AB - The C-terminal boundary of primary sequence of the Bacillus subtilis PAP115 endo beta-1,4-glucanase (EG) required for stable catalytic activity has been mapped by site-directed mutagenesis using Escherichia coli as host. The 52 kDa cel gene product, EG470 and a 33 kDa mutant (EG300), lacking 170 residues through a nonsense mutation at the leucine-330 codon of the gene, exhibited similar patterns of enzymatic activity and pH optima using cellooligopentaose as substrate. CD spectra indicated that the bulk of the alpha-helical secondary structure in EG470 was contained within EG300. However, relative to EG470, the specific activity of EG300 was 3- to 4-fold lower with amorphous cellulose as substrate and approximately 4- to 5-fold higher with carboxymethylcellulose (soluble cellulose). These results along with data which show that EG470 binding capacity to microcrystalline cellulose is approximately 11 times more than that of EG300, demonstrate the importance of residues 330-499 for non-catalytic binding of cellulose. A construct of the cel gene carrying a deletion of codons 330-499 and an insertion of a nonsense codon at leucine-330, was further used to make mutants EG296 and EG291 with nonsense codon substitutions at arginine-326 and serine-321, respectively. Western analysis using EG-specific antiserum revealed that relative losses in enzymatic activity of EG296 (50%) and EG291 (95%) could be accounted for by the extent of their proteolysis, signifying a marked destabilization of these enzymes by removal of only a few amino acids. PMID- 1518793 TI - Mutant forms of beta-galactosidase with an altered requirement for magnesium ions. AB - By random approaches we have previously isolated many variants of Escherichia coli beta-galactosidase within a short contiguous tract near the N-terminus (residues 8-12 of wild-type enzyme), some of which have increased stability towards heat and denaturants. The activity of these mutants was originally analysed and quantitated in situ in activity gels without the addition of magnesium ions to the buffer system. We now show that the improved stability is only observable under such conditions of limiting magnesium ion concentrations or in the presence of appropriate concentrations of a metal chelator. In the presence of EDTA, purified preparations of one of these mutant enzymes were much more resistant to denaturants than wild-type, but this differential was completely nullified in the presence of 1 mM Mg2+. However, the stability of this mutant enzyme in EDTA was lower than that shown by it, or the wild-type enzyme, in the presence of magnesium ions. In addition, certain alterations within another N-terminal tract (residues 27-31 of wild-type) resulted in enzymes with greater dependence on Mg2+ than natural beta-galactosidase. We conclude that a small number of residue changes in a large protein can profoundly modulate the requirement for metal ion stabilization, allowing partial abrogation of this need in certain cases. Thus, some enzymes which require divalent metal ions for structural purposes only may be engineered towards metal independence. PMID- 1518794 TI - Complex additivity of the effects of suppressor mutations in differing protein environments. AB - In the alpha-complementation of beta-galactosidase, a defective beta galactosidase protein interacts with an autologous peptide fragment (alpha peptide) to restore enzymatic activity. Within a specific site of a defective alpha-peptide we have previously isolated a large number of mutations, many of which suppress the functional defect. The alpha-peptide was originally defective due to both insertional and substitutional sequence alterations near its N terminus, which provided an increase in the sensitivity of detection of (suppressor) secondary mutations which conferred improved function. We have now studied the effects of the suppressor mutations when the primary deleterious mutations are sequentially reversed. This was done in intact beta-galactosidase, as we have shown that mutations in the alpha-peptide have related functional effects in the whole protein. Evidence was obtained showing that the effects of at least some suppressor mutations were not simply additive when the mutations are placed into the original wild-type protein environment. One suppressor appeared to function less effectively in the normal environment, while another when tested in the same manner functioned at a relatively increased level. This failure to show simple additivity may be attributable to the physical proximity of the original defective mutations and the introduced suppressors. Nevertheless, even in such cases it may be feasible to use a defective protein as a sensitive starting point for the identification of mutations which improve the wild-type protein. PMID- 1518795 TI - Active papain renatured and processed from insoluble recombinant propapain expressed in Escherichia coli. AB - For the first time the pro-form of a recombinant cysteine proteinase has been expressed at a high level in Escherichia coli. This inactive precursor can subsequently be processed to yield active enzyme. Sufficient protein can be produced using this system for X-ray crystallographic structure studies of engineered proteinases. A cDNA clone encoding propapain, a precursor of the papaya proteinase, papain, was expressed in E. coli using a T7 polymerase expression system. Insoluble recombinant protein was solubilized in 6 M guanidine hydrochloride and 10 mM dithiothreitol, at pH 8.6. A protein-glutathione mixed disulphide was formed by dilution into oxidized glutathione and 6 M GuHCl, also at pH 8.6. Final refolding and disulphide bond formation was induced by dilution into 3 mM cysteine at pH 8.6. Renatured propapain was processed to active papain at pH 4.0 in the presence of excess cysteine. Final processing could be inhibited by the specific cysteine proteinase inhibitors E64 and leupeptin, but not by pepstatin, PMSF or EDTA. This indicates that final processing was due to a cysteine proteinase and suggests that an autocatalytic event is required for papain maturation. PMID- 1518797 TI - Efficient deletion mutagenesis by PCR. PMID- 1518796 TI - Over-production of 5-enolpyruvylshikimate-3-phosphate synthase in Escherichia coli: use of the T7 promoter. AB - 5-Enolpyruvylshikimate-3-phosphate (EPSP) synthase, the product of the Escherichia coli aroA gene, has been overproduced in E. coli BL21(lambda DE3) under the control of the T7 gene 10 promoter and ribosome binding site, to a level of approximately 50% of total cell protein. EPSP synthase is the primary target of the post-emergence herbicide, glyphosate, commonly known as Roundup. A simple two step purification is described, which results in 99% pure homogeneous protein (as determined by PAGE). The integrity of the protein has been compared with previously characterized protein from E. coli AB2829(pKD501) by determination of its kinetic parameters, N-terminal protein and DNA sequences, amino acid analysis and 13C-NMR spectroscopy. This new overproducing strain readily provides the gram quantities of highly pure protein required for NMR studies of the active site and the development of novel time-resolved solid-state NMR techniques currently underway in this laboratory. PMID- 1518798 TI - Comments on models for electrostatic effects in proteins. PMID- 1518799 TI - NMR docking of a substrate into the X-ray structure of staphylococcal nuclease. AB - The conformation of the staphylococcal nuclease-bound metal-dTdA complex, previously determined by NMR methods [Weber, D.J., Mullen, G.P., Mildvan, A.S. (1991) Biochemistry 30:7425-7437] was docked into the X-ray structure of the enzyme-Ca(2+)-3',5'-pdTp complex [Loll, P.J., Lattman, E.E. (1989) Proteins: Struct., Funct., Genet. 5:183-201] by superimposing the metal ions, taking into account intermolecular nuclear Overhauser effects from assigned aromatic proton resonances of Tyr-85, Tyr-113, and Tyr-115 to proton resonances of the leaving dA moiety of dTdA, and energy minimization to relieve small overlaps. The proton resonances of the Phe, Tyr, and Trp residues of the enzyme in the ternary enzyme La(3+)-dTdA complex were sequence specifically assigned by 2D phase-sensitive NOESY, with and without deuteration of the aromatic protons of the Tyr residues, and by 2D heteronuclear multiple quantum correlation (HMQC) spectroscopy and 3D NOESY-HMQC spectroscopy with 15N labeling. While resonances of most Phe, Tyr and Trp residues were unshifted by the substrate dTdA from those found in the enzyme La(3+)-3',5'-pdTp complex and the enzyme-Ca(2+)-3',5'-pdTp complex, proton resonances of Tyr-85, Tyr-113, Tyr-115, and Phe-34 were shifted by 0.08 to 0.33 ppm and the 15N resonance of Tyr-113 was shifted by 2.1 ppm by the presence of substrate. The optimized position of enzyme-bound dTdA shows the 5'-dA leaving group to partially overlap the inhibitor, 3',5'-pdTp (in the X-ray structure). The 3'-TMP moiety of dTdA points toward the solvent in a channel defined by Ile 18, Asp-19, Thr-22, Lys-45, and His-46. The phosphate of dTdA is coordinated by the metal, and an adjacent inner sphere water ligand is positioned to donate a hydrogen bond to the general base Glu-43 and to attack the phosphorus with inversion. Arg-35 and Arg-87 donate monodentate hydrogen bonds to different phosphate oxygens of dTdA, with Arg-87 positioned to protonate the leaving 5' oxygen of dA, thus clarifying the mechanism of hydrolysis. Model building of an additional 5'-dGMP onto the 3'-oxygen of dA placed this third nucleotide onto a surface cleft near residues Glu-80, Asp-83, Lys-84, and Tyr-115 with its 3'-OH group accessible to the solvent, thus defining the size of the substrate binding site as accommodating a trinucleotide. PMID- 1518800 TI - Molecular dynamics characterization of the active cavity of carboxypeptidase A and some of its inhibitor adducts. AB - Molecular dynamics (MD) calculations have been performed on carboxypeptidase A and on its adducts with inhibitors, such as d-phenylalanine (dPhe) and acetate. The catalytically essential zinc ion present in the protein was explicitly included in all the simulations. The simulation was carried out over a sphere of 15 A centered on the zinc ion. The crystallographic water molecules were explicitly taken into account; then the protein was solvated with a 18 A sphere of water molecules. MD calculations were carried out for 45-60 ps. There is no large deviation from the available X-ray structures of native and the dPhe adduct for the MD structures. Average MD structures were calculated starting from the X ray structure of the dPhe adduct, and, from a structure obtained by docking the inhibitor in the native structure. Comparison between these two structures and with that of the native protein shows that some of the key variations produced by inhibitor binding are reproduced by MD calculations. Addition of acetate induces structural changes relevant for the understanding of the interaction network in the active cavity. The structural variations induced by different inhibitors are examined. The effects of these interactions on the catalytic mechanism and on the binding of substrate are discussed. PMID- 1518801 TI - NMR restraint analysis of transforming growth factor alpha: a key component for NMR structure refinement. AB - Structures of the protein, transforming growth factor alpha (TGF-alpha), have been derived from NMR data using distance geometry and subsequent energy refinement. Analysis of the sequential NOE distance bounds using a template algorithm provides a check for consistency in the calculation of bounds, stereospecific assignment of prochiral centers, and secondary structure assignment. Application of the template algorithm to the long range NOEs found within the NMR data sets collected at pH 6.3 and pH 3.4 is used to assess the confidence levels for the accuracy of the structures obtained from modeling. The method also provides critical insight in differentiating regions of the structure that are well defined from those that are not. Use of the restraint analysis protocol is shown to be a powerful adjunct to currently used methods for the assignment of protein structures from NMR data. PMID- 1518802 TI - Modeling microdomains: the surface area of globin helices. AB - The accessible surface areas of 53 high-resolution globin helices are correlated with molecular weight. The linear fit is assessed for statistical accuracy using a boot-strap analysis, and by comparison to the areas of 13 ideal polyalanine alpha-helices. The accessible area of the unfolded helices is compared with the folded values before helix-helix packing. An analytical physical model is presented to explain the correlation, and to provide an analytical value for the surface area parameter in the diffusion-collision model of protein folding. PMID- 1518803 TI - Amino acid substitution analysis of E. coli thymidylate synthase: the study of a highly conserved region at the N-terminus. AB - Amino acid substitution analysis within a highly conserved region of Escherichia coli thymidylate synthase (TS), using suppression of amber mutations by tRNA suppressors, has yielded a bank of 124 new mutationally altered TS proteins. These mutant proteins have been used to study the structure-function relationship of the Escherichia coli TS protein at the N-terminus corresponding to residues 20 through 35. This region contains a block of amino acids whose sequence has been well conserved among other known TS proteins from various organisms. Positions 20 through 25 contain a surface loop structure and positions 26 through 35 encompass a beta-strand. We find that residues surrounding a beta-bulge structure within the beta-strand are particularly sensitive to amino acid substitution, suggesting that this structure is maintained by a highly ordered packing arrangement. Three residues in the surface loop that are present at the base of the substrate binding pocket are also sensitive to amino acid substitution. The remainder of the conserved sites, including those at the dimer interface, are tolerant to most, if not all, of the substitutions tested. PMID- 1518804 TI - Pancreatic spasmolytic polypeptide: crystallization, circular dichroism analysis, and preliminary X-ray diffraction studies. AB - Pancreatic spasmolytic polypeptide (PSP) isolated from porcine pancreas has been crystallized by the hanging drop vapor diffusion method. Crystals suitable for X ray diffraction analysis were grown at pH 4.7 from a solution of 6% saturated ammonium sulfate. The space group is orthorhombic I222 or I2(1)2(1)2(1) with unit cell parameters a = 54.38 A, b = 72.29 A, and c = 180.85 A. There are three molecules of PSP per asymmetric unit and a water content of 46.9%. The crystals diffracts to an estimated resolution of 2.7 A. The far-UV CD spectrum of PSP shows some exceptional features which cannot be accounted for thoroughly in terms of standard secondary structures commonly seen in protein CD spectroscopy. With this limitation, the secondary structure analysis predicts 15% alpha-helix, between 10 and 20% antiparallel beta-strand, 10% parallel beta-strand, 15% turn, and 25 to 40% of other structures. PMID- 1518805 TI - Isolation and characterization of a full-length cDNA coding for an adipose differentiation-related protein. AB - We have previously isolated from a 1246 adipocyte cDNA library a cDNA clone called 154, corresponding to a mRNA that increases abundantly at a very early time during the differentiation of 1246 adipocytes and in adipocyte precursors in primary culture. We show here that the mRNA encoded by this cDNA is expressed abundantly and preferentially in mouse fat pads. A full-length cDNA for clone 154 was isolated by the RACE (rapid amplification of cDNA ends) protocol. Sequence analysis of this cDNA indicates that it encodes a protein of the 425 amino acids [tentatively named adipose differentiation-related protein (ADRP)] that does not have any similarity with sequences contained in the GenBank DNA and Protein Identification Resource protein data bases. Immunoblot of 1246 cell extracts with an antibody raised against the expressed ADRP shows that the 1246 cells contain a 50-kDa protein, the production of which increases as the cells differentiate. Localization of ADRP in 1246 cells indicates that ADRP is absent from nuclear and cytosolic fractions and is found as a membrane-associated protein. These results demonstrate that adipocyte differentiation is accompanied by early expression of a mRNA encoding a membrane-associated adipose differentiation related protein that is adipose tissue specific in vivo. PMID- 1518806 TI - In vivo self-association of the Drosophila rel-protein dorsal. AB - The Drosophila morphogen dorsal, KBF1, NF-kappa B, and the proto-oncogene c-rel belong to the rel family of transcription factors whose function is regulated post-translationally by selective nuclear import. In the early Drosophila embryo, dorsal protein is proposed to be retained in the cytoplasm through its interaction with cactus protein. The maternal dorsal group genes constitute a signal transduction pathway, which results in targeting cytoplasmic dorsal protein into the nuclei of the syncytial blastoderm embryo, in a ventral-to dorsal gradient. The asymmetric transcriptional regulation of zygotic genes along the dorsoventral axis by the dorsal morphogen gradient establishes embryonic dorsoventral polarity. In the lymphocytes, the functional equivalent of cactus is I kappa B, which appears to retain NF-kappa B in the cytoplasm. This retention is relieved by extracellular signals in tissue culture. NF-kappa B and rel proteins each are known to function as oligomeric complexes. Here we present genetic and biochemical evidence for the existence and functional importance of an oligomeric dorsal complex in vivo. PMID- 1518807 TI - Mutational spectrum at the Hprt locus in splenic T cells of B6C3F1 mice exposed to N-ethyl-N-nitrosourea. AB - We have determined the mutational spectrum of N-ethyl-N-nitrosourea (ENU) in exon 3 of the hypoxanthine (guanine) phosphoribosyltransferase gene (Hprt) in splenic T cells following in vivo exposure of male B6C3F1 mice (5-7 weeks old) to ENU. Hprt- mutants were isolated by culturing splenic T cells in microtiter dishes containing medium supplemented with interleukin 2, concanavalin A, and 6 thioguanine. DNA was extracted from 6-thioguanine-resistant colonies and amplified by the polymerase chain reaction (PCR) using primers flanking Hprt exon 3. Identification of mutant sequences and purification of mutant DNA from contaminating wild-type Hprt DNA was accomplished by denaturing-gradient gel electrophoresis. Purified mutant DNA was then sequenced. Treatment of mice with ENU at 40 mg/kg of body weight produced a Hprt- mutant frequency of 7.3 x 10(-5) in splenic T cells, approximately 35-fold above background levels. Sixty-nine of the 521 Hprt- mutants analyzed contained mutations in exon 3 (13%). Transversions and transitions at A.T base pairs dominated the spectrum; 62 of the 69 exon 3 mutations were at A.T base pairs (14 different sites). Thirteen of 14 thymine bases undergoing mutation (61 of 62 mutations at A.T bases) were located on the nontranscribed strand of exon 3. The majority of the remaining mutations (6 of 69) were transitions at a single G.C base pair. These results suggest the importance of thymidine alkylation in ENU-induced mutagenesis in vivo. The mouse Hprt- T-cell cloning/sequencing assay described here may represent a useful system for studying the molecular mechanism of chemically induced mutation occurring in vivo in an endogenous gene. PMID- 1518808 TI - A monomeric von Willebrand factor fragment, Leu-504--Lys-728, inhibits von Willebrand factor interaction with glycoprotein Ib-IX [corrected]. AB - von Willebrand factor interaction with glycoprotein Ib alpha (GPIb alpha) plays a critical role in the initial phase of platelet adhesion at high shear rates, and it may also play a role in platelet thrombus formation in partially occluded arteries. Previous studies have indicated that two peptides, Cys-474--Pro-488 (peptide 153) and Ser-692--Pro-708 (peptide 154), inhibit von Willebrand factor- GPIb alpha interaction. We have expressed a recombinant fragment of von Willebrand factor, Leu-504--Lys-728 [corrected], with a single intrachain disulfide bond linking residues Cys-509--Cys-695 and examined its ability to inhibit von Willebrand factor--GPIb alpha interactions and platelet adhesion at high shear forces. This recombinant fragment, named VCL, inhibits ristocetin induced, botrocetin-induced, and asialo-von Willebrand factor-induced platelet aggregation and binding to platelets at an IC50 = 0.011-0.260 microM, significantly lower than the IC50 of peptide 153 or 154, IC50 = 86-700 microM. Peptides 153 and 154 did not result in any inhibition of platelet adhesion (IC50 greater than 500 microM). In contrast, VCL inhibited 50% of platelet adhesion at 0.94 microM and at 7.6 microM inhibited greater than 80% of platelet adhesion to human umbilical artery subendothelium at high shear forces. VCL inhibited the contact and spreading of platelets and also caused a marked decrease in thrombus formation. These studies indicate that VCL may be an effective antithrombotic agent in preventing arterial thrombus formation in areas of high shear force. PMID- 1518809 TI - Ligand occupancy mimicked by single residue substitutions in a receptor: transmembrane signaling induced by mutation. AB - We used mixed, mutagenic oligonucleotides to create single amino acid substitutions in the bacterial chemoreceptor Trg. Mutagenesis was directed at a 20-residue segment of the periplasmic domain implicated in ligand recognition. Transmembrane signaling by the mutant receptors was assayed in vivo by monitoring adaptational covalent modification. Among 20 functionally altered but stable receptors there were two distinct signaling phenotypes. Insensitive receptors did not signal upon stimulation and thus appeared defective in productive ligand interaction. Mimicked-occupancy receptors exhibited transmembrane signaling without ligand. Many mimicked-occupancy receptors produced additional signaling upon ligand binding and in appropriate conditions mediated effective chemotaxis; most insensitive receptors did not. Like normal receptors with one binding site occupied, mimicked-occupancy proteins adapted to persistent transmembrane signaling by increased methylation and thus could respond to other stimuli. Signaling phenotypes were strikingly segregated by residue position. Substitutions mimicking ligand occupancy occurred in half the segment, and those creating insensitive phenotypes occurred in the other half. These observations could be related to the three-dimensional structure of the periplasmic domain of the Tar(s) chemoreceptor. Insensitive substitutions occurred near the distal end of helix 1, where bulky protein ligands could interact; occupancy-mimicking substitutions were on the same helix at positions buried in the subunit interface between helices 1 and 1'. Thus perturbation of the interface induced transmembrane signaling, implicating changes at that interface in signal transduction, a conclusion consistent with differences in crystal structures of unoccupied and ligand-occupied Tar(s). PMID- 1518810 TI - Phosphorylation of the retinoblastoma protein by cdk2. AB - The retinoblastoma gene product (the RB protein) is phosphorylated in a cell cycle-dependent manner and this modification is believed to be important for cells to progress through the cell cycle. We found that purified cdk2 (cyclin dependent kinase/cell division kinase 2) can phosphorylate the RB protein in vitro at the sites phosphorylated in the cell. The timing of activation of cdk2 in the cell cycle was similar to that of the onset of phosphorylation of the RB protein. The kinase coprecipitated with the RB protein also exhibited a similar substrate specificity to cdk2 and a similar time course of activation during the cell cycle. We further showed that cdk2 formed a complex with the RB protein in vitro and that its formation was not competitively inhibited by the simian virus 40 large T antigen. These observations suggest that cdk2 or a cdk2-related protein is involved in the cell cycle-dependent phosphorylation of the RB protein. PMID- 1518811 TI - Genomic targeting with a positive-selection lox integration vector allows highly reproducible gene expression in mammalian cells. AB - Stable transformants of mammalian cells from gene transfer often show extreme variability in expression of the introduced transgene. This occurs from the highly variable number of copies integrated into the genome and from position effects on gene expression due to random integration. We have eliminated both of these constraints on predictable gene expression by use of a lox recombination vector. The positive selection vector system is designed to directly select Cre mediated DNA integration at a lox target previously placed into the genome of cultured mammalian cells. Proper targeting activates expression of a defective lox-neomycin phosphotransferase (neo) fusion gene target. With CHO cell lines containing this target, almost all of the selected transformants (54 of 56 independent G418-resistant colonies) were simple single-copy integrants of the targeting DNA. To monitor gene expression at a single chromosomal site, we used a beta-actin promoter-lacZ reporter construct. Independent G418-resistant colonies from site-specific integration of the reporter gene all showed nearly identical levels of beta-galactosidase activity when the reporter construct integrated at a particular chromosomal position. The same construct integrated at a second chromosomal position exhibited a slightly different level of activity, characteristic of that second position. These results show that Cre-mediated site specific integration can facilitate the construction of isogenic cell lines and thereby permit reproducible gene expression in stably transformed cell lines. PMID- 1518812 TI - Hagfish humoral defense protein exhibits structural and functional homology with mammalian complement components. AB - A genomic clone and cDNA fragment encoding a portion of a humoral recognition molecule from the hagfish were isolated and sequenced. The serum protein has previously been described as having structural features that are immunoglobulin like. Amino acid sequence obtained from the 77-kDa H1 heavy chain facilitated the isolation of a genomic clone containing at least two coding regions. Through use of primers derived from the genomic sequences, a 231-base-pair cDNA fragment was obtained by PCR from liver RNA. Comparison of the deduced 120-amino acid sequence from the N terminus of H1 with known protein sequences revealed substantial sequence similarity with the beta chain of the murine fourth complement component C4 and with the related third and fifth complement molecules C5 and C3 and the major histocompatibility complex-encoded sex-limited protein. Observation of structural and functional similarities associated with the sequence similarity indicate that these molecules share an evolutionary relationship: the polypeptide chain structure of hagfish complement-like protein (CLP) resembles that of C4; CLP contains a hidden thioester group on the 70-kDa chain; CLP binds to streptococcal cells and enhances the phagocytosis of yeast by hagfish leukocytes. These data suggest that CLP forms part of a non-clonally-derived complement related humoral defense system in the hagfish. PMID- 1518813 TI - Cationic lipids direct a viral glycoprotein into the class I major histocompatibility complex antigen-presentation pathway. AB - Recombinant glycoprotein B (gB) of herpes simplex virus (HSV) was processed and presented by class I major histocompatibility complex (MHC) molecules after delivery into cells by using N-[1-(2,3-dioleoyloxy)propyl]-N,N,N trimethylammonium methyl sulfate (DOTAP), a commercially available cationic lipid used for DNA transfection. Cells treated with DOTAP-associated gB were susceptible to lysis by class I MHC-restricted, HSV-specific cytotoxic T lymphocytes (CTL), and the treated cells restimulated memory gB-specific CTL activity in spleen cells from HSV-infected mice. gB-specific CTL responses were detected in mice immunized with recombinant gB and DOTAP but not in those receiving gB emulsified in complete Freund's adjuvant. Thus, cationic lipids may facilitate induction of CD8+ T-cell responses in vaccinations with recombinant antigens, and they may serve as readily available reagents for dissecting class I MHC immunity to viruses and other intracellular pathogens. PMID- 1518814 TI - Electrical method for detection of endothelial cell shape change in real time: assessment of endothelial barrier function. AB - We have developed an electrical method to study endothelial cell shape changes in real time in order to examine the mechanisms of alterations in the endothelial barrier function. Endothelial shape changes were quantified by using a monolayer of endothelial cells grown on a small (10(-3) cm2) evaporated gold electrode and measuring the changes in electrical impedance. Bovine pulmonary microvessel endothelial cells and bovine pulmonary artery endothelial cells were used to study the effects of alpha-thrombin on cell-shape dynamics by the impedance measurement. alpha-Thrombin produced a dose-dependent decrease in impedance that occurred within 0.5 min in both cell types, indicative of retraction of endothelial cells and widening of interendothelial junctions because of "rounding up" of the cells. The alpha-thrombin-induced decrease in impedance persisted for approximately 2 hr, after which the value recovered to basal levels. Pretreatment of endothelial cells with the protein kinase C inhibitor, calphostin C, or with 8 bromoadenosine 3',5'-cyclic monophosphate prevented the decreased impedance, suggesting that the endothelial cell change is modulated by activation of second messenger pathways. The alpha-thrombin-induced decrease in impedance was in agreement with the previously observed increases in transendothelial albumin permeability and evidence of formation of intercellular gaps after alpha-thrombin challenge. The impedance measurement may be a valuable in vitro method for the assessment of mechanisms of decreased endothelial barrier function occurring with inflammatory mediators. Since the rapidly occurring changes in endothelial cell shape in response to mediators such as thrombin are mediated activation of second messenger pathways, the ability to monitor endothelial cell dynamics in real time may provide insights into the signal-transduction events mediating the increased endothelial permeability. PMID- 1518815 TI - Multicellular oxidant defense in unicellular organisms. AB - Although catalase is thought to be a major defense against hydrogen peroxide (H2O2), the catalase activity within individual Escherichia coli fails to protect against exogenous H2O2. Contrary to earlier reports, we find that dilute suspensions of wild-type and catalase-deficient E. coli are identical in their sensitivity to H2O2, perhaps because even wild-type, catalase-positive E. coli cannot maintain an internal/external concentration gradient of this highly diffusible oxidant. However, concentrated suspensions or colonies of catalase positive E. coli do preferentially survive H2O2 challenge and can even cross protect adjacent catalase-deficient organisms. Furthermore, high-density catalase positive--but not catalase-negative--E. coli can survive and multiply in the presence of competitive, peroxide-generating streptococci. These observations support the concept that bacterial catalase may defend colonial, but not individual, E. coli against environmental H2O2. Group protection by the activity of enzymes that mitigate oxidative stress may have been a driving force in the evolution of multicellular organisms. PMID- 1518816 TI - Influenza virus hemagglutinin HA-2 N-terminal fusogenic peptides augment gene transfer by transferrin-polylysine-DNA complexes: toward a synthetic virus-like gene-transfer vehicle. AB - Complexes containing plasmid DNA, transferrin-polylysine conjugates, and polylysine-conjugated peptides derived from the N-terminal sequence of the influenza virus hemagglutinin subunit HA-2 have been used for the transfer of luciferase or beta-galactosidase marker genes to K562 cells, HeLa cells, and BNL CL.2 hepatocytes. These DNA complexes mimic the entry of viruses into cells, as they contain functions for (i) the packaging of the nucleic acid with polylysine, (ii) the attachment to the cell and receptor-mediated endocytosis with transferrin as a ligand, and (iii) the release from endosomes by using membrane disrupting influenza peptides. The presence of these influenza peptide conjugates in the DNA complexes renders the complexes active in membrane disruption in a liposome leakage assay and results in a substantial augmentation of the transferrin-polylysine-mediated gene transfer. PMID- 1518817 TI - A trinucleotide can promote metal ion-dependent specific cleavage of RNA. AB - Nucleotide sequence and metal ion requirements for Mn(2+)-dependent self-cleavage of an RNA 31 nucleotides long [Dange, V., Van Atta, R. B. & Hecht, S. M. (1990) Science 248, 585-588] were examined by analysis of the site-specific cleavage activity of substitution and deletion mutants as well as complexes assembled from fragments of this RNA. A complex of UUU and GAAACp allows specific cleavage between G and A at 37 degrees C and pH 7.5. Additional nucleotides flanking the oligonucleotides in the minimal complex are not necessary for the cleavage reaction to take place but can affect the rate of the reaction. The 2'-OH groups of uridine residues do not participate in catalysis since both poly(U) and poly(dU) can promote the specific cleavage reaction in trans. Cd2+ ions can also promote the specific cleavage reaction and Mg2+ ions (which are inactive alone), under certain conditions, can enhance the Mn(2+)-induced cleavage of RNA. PMID- 1518818 TI - Equilibrium and kinetic constants for the thiol-disulfide interchange reaction between glutathione and dithiothreitol. AB - The equilibrium and rate constants for the reaction between oxidized and reduced glutathione and oxidized and reduced dithiothreitol have been determined at several pH values and temperatures. The measurements involve approach to equilibrium from both directions, quenching of the reaction by lowering the pH or by addition of methyl methanethiosulfonate, separation of reactants and products by reverse-phase HPLC, and determination of their concentrations. Analysis of reaction mixtures was carried out at various times to assure that equilibrium had been reached and to determine kinetic constants prior to the attainment of equilibrium. PMID- 1518819 TI - Murine serum amyloid A3 is a high density apolipoprotein and is secreted by macrophages. AB - The serum amyloid A (SAA) proteins make up a multigene family of apolipoproteins associated with high density lipoproteins. They are of ancient origin; the finding of a highly homologous protein in mammals and ducks indicates that SAAs have been in existence for at least 300 million years. The interspecies similarity among the SAAs makes the mouse, in which they have been most thoroughly studied, a reasonable model to use for defining the function(s) of this family of proteins in humans. Originally it was observed that the SAA proteins were made in the liver and represented a set of proteins belonging to acute-phase reactants. SAA3 is a unique member of the SAA multigene family in mice in that its mRNA is also expressed in extrahepatic tissues by a variety of cell types, mainly macrophages and adipocytes. To date, nothing has been reported regarding the fate or function of the SAA3 translation product. To identify the SAA3 protein, we developed SAA3-specific antibodies by immunizing rabbits against a portion of SAA3 protein synthesized in a bacterial fusion protein expression system. Electroimmunoblot analysis of serum and lipoprotein fractions of it showed SAA3 to be associated with high density lipoproteins of mice treated with lipopolysaccharide. Furthermore, a continuous mouse macrophage cell line (J 774.1), when exposed to lipopolysaccharide, expressed SAA3 mRNA in a dose dependent manner and secreted SAA3 protein. The expression and secretion of SAA3 by macrophages stimulated with lipopolysaccharide suggest a role for this SAA in local responses to injury and inflammation. PMID- 1518820 TI - Inverted repeat structure of the Sry locus in mice. AB - The testis-determining gene Sry is located on the short arm of the mouse Y chromosome in a region known to have undergone duplications and rearrangements in comparison with the equivalent portion of the human Y chromosome. Detailed analysis of the Sry genomic locus reveals a further difference in that the mouse Sry open reading frame lies within 2.8 kilobases of unique sequence at the center of a large inverted repeat. This repeat, which is found in both Mus musculus musculus and Mus musculus domesticus Y chromosomes, is not present at the human SRY locus. Recombination involving the repeat region may have led to an 11 kilobase deletion, precisely excising Sry in a line of XY female mice. PMID- 1518821 TI - CD4 and its role in infection of rabbit cell lines by human immunodeficiency virus type 1. AB - Human CD4 (HuCD4) is the principal receptor for human immunodeficiency virus type 1 (HIV-1) in human cell infection. Susceptibility of rabbit cell lines to infection with HIV-1 raised questions concerning whether a CD4 homolog serves as HIV-1 receptor on rabbit cells. Sequence comparisons of rabbit CD4 (RbCD4) cloned from a rabbit thymus cDNA library showed that 6 of the 18 residues implicated in HIV-1 binding by CD4 differ between the human and rabbit proteins. No correlation between RbCD4 expression by rabbit cell lines and their ability to support HIV-1 infection was seen. Transfection of RbCD4-negative, HTLV-I-transformed cell lines with HuCD4 significantly enhanced HIV-1 infectivity, suggesting that these lines lack a receptor present on other RbCD4-negative lines that produce high levels of p24 in their native state. Inhibition of HIV-1 infection with soluble HuCD4 was demonstrated for all rabbit lines tested, but complete inhibition was obtained only with a rabbit T-cell line expressing RbCD4 and with HuCD4 transfectants. The results suggest that HIV-1 infection of the RbCD4-positive line proceeds through a receptor similar to HuCD4 but that an additional receptor or receptors may serve this purpose in RbCD4-negative lines. PMID- 1518822 TI - Elevated sister chromatid exchange phenotype of Bloom syndrome cells is complemented by human chromosome 15. AB - Bloom syndrome (BSx) is a rare autosomal-recessive chromosome-instability disorder manifested by a constellation of clinical features including a significant predisposition to early onset of neoplasia. BSx cells display cytogenetic abnormalities, the pathognomonic feature being an increased rate of spontaneous sister chromatid exchanges (SCEs), 10- to 15-fold more frequent than SCEs seen in control cells. Identification of the primary biochemical defect in BSx and its relationship to SCE frequency and neoplasia have been complicated by reports that BSx cell lines exhibit defects in the structure and/or activity of a number of different enzymes. The rare occurrence of the disorder and lack of informative families have precluded mapping of the primary defect by standard linkage analysis. We have utilized BSx cells as recipients for microcell-mediated chromosome transfer to map a locus that renders complementation of the elevated SCE phenotype. Studies with the BSx cell line GM08505 demonstrated a stable frequency of SCEs 10-fold higher than control values, offering a phenotype suitable for complementation studies. Transfer of different independent human chromosomes from somatic cell hybrids into BSx cells permitted identification of a single chromosome that dramatically reduced the SCE frequency to a level near that seen in control cells. Detailed characterization revealed this complementing element to be human chromosome 15. PMID- 1518823 TI - Immunophotodiagnosis of colon carcinomas in patients injected with fluoresceinated chimeric antibodies against carcinoembryonic antigen. AB - Based on previous experiments in nude mice, showing that fluoresceinated monoclonal antibodies against carcinoembryonic antigen localized specifically in human carcinoma xenografts and could be detected by laser-induced fluorescence, we performed a feasibility study to determine whether this immunophotodiagnosis method could be applied in the clinic. Six patients, with known primary colorectal carcinoma, received an i.v. injection of 4.5 or 9 mg of mouse-human chimeric anti-carcinoembryonic antigen monoclonal antibody coupled with 0.10-0.28 mg of fluorescein (molar ratio 1/10 to 1/14). The monoclonal antibody was also labeled with 0.2-0.4 mCi of 125I (1 Ci = 37 GBq). Photodetection of the tumor was done ex vivo on surgically resected tissues for the six patients and in vivo by fluorescence rectosigmoidoscopy for the sixth patient. Upon laser irradiation, clearly detectable heterogeneous green fluorescence from the dye-antibody conjugate was visually observed on all six tumors; almost no such fluorescence was detectable on normal mucosa. The yellowish tissue autofluorescence, which was emitted from both tumor and normal mucosa, could be subtracted by real-time image processing. Radioactivity measurements confirmed the specificity of tumor localization by the conjugate; tissue concentrations of up to 0.059% injected dose per g of tumor and 10 times less (0.006%) per g of normal mucosa were found. The overall results demonstrate the feasibility of tumor immunophotodiagnosis at the clinical level. PMID- 1518824 TI - Intranuclear Ca2+ transients during neurite regeneration of an adult mammalian neuron. AB - Depolarization-induced increases in cytoplasmic and intranuclear Ca2+ were visualized in adult mammalian dorsal root ganglion (DRG) neurons during different stages of neurite extension by using confocal laser scanning microscopy and the long-wavelength Ca2+ indicator dye fluo 3-AM (acetoxymethyl ester of fluo 3). In neurons beginning to extend neurites, depolarization led to pronounced increases in nuclear and nucleolar Ca2+ levels severalfold greater than corresponding increases in the cytoplasm. The nucleolar Ca2+ signal often exceeded that of the nucleus, indicating regional heterogeneity of the nucleus. The subcellular calcium transients were dependent on extracellular Ca2+ and the level of depolarization, indicating the importance of transmembrane Ca2+ fluxes in triggering the nuclear events. After neurite extension, the nuclear Ca2+ signals were attenuated and never exceeded cytoplasmic levels. These results indicate that activity-dependent modulation of intranuclear Ca2+ levels is greater in DRG neurons during early neurite extension. Given the importance of Ca2+ in gene expression, the results may be relevant to Ca(2+)-dependent nuclear events responsible for axonal regeneration. PMID- 1518825 TI - Alloantigen recognition by two human natural killer cell clones is associated with HLA-C or a closely linked gene. AB - Human natural killer (NK) cells with the CD3- CD16+ phenotype recognize allospecificities on normal T-cell blasts. The NK-defined specificity 1 (NK-1) is recessively inherited and has been mapped to the major histocompatibility complex between the complement gene cluster and HLA-A. A gene for NK-1, however, has not been identified. Here we demonstrate that NK-1 and the recently defined NK specificity 2 (NK-2) are reciprocally associated with homozygosity for a diallelic polymorphism at amino acid positions 77 and 80 in the putative peptide binding site of HLA-C (P less than 10(-5)). NK-cell recognition of allogeneic cells may, therefore, be controlled by HLA-C itself or by a closely linked gene(s), which dominantly prevents (resistance alleles) or recessively permits (susceptibility alleles) recognition of still-unknown target determinants. PMID- 1518826 TI - Heterotetrameric structure of the human progesterone receptor. AB - Nonactivated progesterone receptors in extracts of human T47D mammary carcinoma cells were investigated. Chemical cross-linking with dimethyl suberimidate resulted in complete stabilization of the A and B receptors with an average molecular mass of 340 kDa. For analyzing the subunit structure, we concentrated on the larger B receptor, which was separated from the A form by immunoaffinity chromatography. Progressive cross-linking of the photoaffinity-labeled receptor resulted in patterns of labeled bands in SDS gels, which are indicative of a heterotetrameric structure. It consists of one receptor polypeptide in association with two 90-kDa subunits and one polypeptide of approximately 60 kDa. The completely cross-linked B receptor has a molecular mass of approximately 390 kDa. To identify the subunits, the oligomeric B receptor was cross-linked with a cleavable bisimidate, highly purified by immunoaffinity chromatography, and analyzed by gel electrophoresis and immunoblotting. The receptor polypeptide has a mass of 116.5 kDa. The 90-kDa band was identified as the heat shock protein hsp90 and was roughly twice as intense as the receptor polypeptide. By use of specific antibodies, we identified the fourth receptor subunit as a 59-kDa protein (p59); we did not obtain any evidence for the heat shock protein hsp70 being a receptor component. We suggest an analogous heterotetrameric structure for the nonactivated A receptor. PMID- 1518827 TI - Primary structure, import, and assembly of the yeast homolog of succinate dehydrogenase flavoprotein. AB - We have isolated a homolog for the flavoprotein subunit of succinate dehydrogenase [succinate:(acceptor) oxidoreductase, EC 1.3.99.1] from Saccharomyces cerevisiae and used the obtained peptide sequences to clone and characterize the corresponding gene. It contained an open reading frame of 1923 base pairs and encoded a protein of 640 amino acids (M(r), 70,238) that showed approximately 49% and approximately 28% identity with the Escherichia coli and Bacillus subtilis enzymes, respectively. All features of the FAD cofactor binding site were completely conserved. Comparison of the deduced protein sequence with the N-terminal sequence determined from the isolated protein revealed an N terminal extension of 28 amino acids that presumably represents a mitochondrial signal sequence. After in vitro transcription and translation, the preprotein was efficiently imported into isolated yeast mitochondria, cleaved to its mature form, and assembled into the membrane-bound succinate dehydrogenase complex. PMID- 1518828 TI - Site-directed mutagenesis of histidine residues involved in Cu(II) binding and reduction by sperm whale myoglobin. AB - Sperm whale myoglobin (Mb) reduces Cu(II) through a site-specific mechanism involving complexation by one or more surface histidine residues. Three mutants of Mb, derived from recombinant wild-type Mb, were designed in which surface histidine residues exhibiting strong Cu(II) binding were replaced with amino acids with comparatively poor metal binding characteristics. The kinetics of Cu(II)(Gly)2 reduction by native Mb, recombinant wild-type Mb, and the mutants were compared. Recombinant wild-type Mb reduced Cu(II) at a rate similar to that of native Mb. Two single mutations (His-48----Ala and His-116----Asp) decreased the rate by 31% and 7%, respectively, relative to wild-type Mb and decreased the rate by 38% and 16%, respectively, relative to native Mb. A double mutation (His 113----Ala, His-116----Asp) decreased the rate only slightly more than the single mutation at His-116. Previous NMR studies showed that His-113 exhibits the strongest Cu(II) binding of all surface histidines, but the present experiments suggest that it plays little or no role in the reduction of Cu(II) by Mb. His-48, located 12.7 A from the Fe(II)-heme, participates in one-third of the redox activity of the protein. His-116 appears to play a minor role in the overall redox activity of Mb, but its involvement shows that Mb has the ability to reduce Cu(II) through a histidine residue located more than 20 A from the Fe(II)-heme. These experiments demonstrate that electron transport from the Fe(II)-heme to site-specifically bound Cu(II) can be mediated through multiple pathways in sperm whale Mb. PMID- 1518829 TI - Hydrolysis and reconjugation of gibberellin A20 glucosyl ester by seedlings of Zea mays L. AB - The [6-2H]glucosyl ester of [17-13C,3H]gibberellin A20 (GA20) was injected into light-grown 14-day-old seedlings of normal, dwarf-1, and dwarf-5 maize (Zea mays L.). The plant material was extracted 24 h later, and the extracts were purified by solvent partitioning, column chromatography, and HPLC. 13C-labeled metabolites were identified from the purified extracts by full-scan gas chromatography/mass spectrometry and selected ion current monitoring in conjunction with Kovats retention indices. The metabolites, [13C]GA20, [13C]GA29, [13C]GA20-13-O glucoside, and [13C]GA29-2-O-glucoside, were identified from normal, dwarf-1, and dwarf-5 seedlings. [13C]GA8 and [13C]GA8-2-O-glucoside were also identified from normal and dwarf-5 seedlings but not from dwarf-1 seedlings. The data provide definitive evidence for the endogenous hydrolysis by the seedlings of the introduced conjugate and its reconjugation to three glucosides. PMID- 1518830 TI - Recombinant human migration inhibitory factor has adjuvant activity. AB - Recombinant human migration inhibitory factor (MIF), isolated through functional expression cloning in COS-1 cells, up-regulates expression of genes encoding HLA DR and interleukin 1 beta (IL-1 beta) and elaboration of IL-1 beta by human monocyte-derived macrophages. Administration of soluble bovine serum albumin or human immunodeficiency virus 120-kDa glycoprotein (HIV gp120) to mice in the presence of recombinant MIF together with incomplete Freund's adjuvant induced a strong T-cell proliferative response comparable to that of complete Freund's adjuvant. Recombinant MIF also increased antibody production, especially of IgG1 and IgM, in mice. Taken together, these results indicate that recombinant MIF may be useful as an adjuvant in the development of vaccines. PMID- 1518831 TI - A homolog of Escherichia coli RecA protein in plastids of higher plants. AB - Studies of chloroplast DNA variations, and several direct experimental observations, indicate the existence of recombination ability in algal and higher plant plastids. However, no studies have been done of the biochemical pathways involved. Using a part of a cyanobacterial recA gene as a probe in Southern blots, we have found homologous sequences in total DNA from Pisum sativum and Arabidopsis thaliana and in a cDNA library from Arabidopsis. A cDNA was cloned and sequenced, and its predicted amino acid sequence is 60.7% identical to that of the cyanobacterial RecA protein. This finding is consistent with our other results showing both DNA strand transfer activity and the existence of a protein of the predicted molecular mass crossreactive with antibodies to Escherichia coli RecA in the stroma of pea chloroplasts. PMID- 1518832 TI - A plant cDNA that partially complements Escherichia coli recA mutations predicts a polypeptide not strongly homologous to RecA proteins. AB - A plant (Arabidopsis thaliana) cDNA previously selected for its ability to partially complement the UV sensitivity of Escherichia coli RecA-UvrC-Phr- mutants and designated DRT100 (DNA-damage repair/toleration) was subcloned into a high-copy-number plasmid and expressed via a bacterial promotor. It increased resistance of RecA-UvrB-Phr- bacteria to mitomycin C and methyl methanesulfonate as well as to UV light. This lack of specificity, and its ability to increase resistance in both UvrB- and UvrC- mutants, suggested that Drt100 activity might be complementing RecA- phenotypes. DRT100 partially complemented three RecA- phenotypes thought to reflect deficiencies in homologous recombination--namely, inability to plate lambda red-gam- phages and P1 phages and to recombinationally integrate donor DNA during conjugal crosses--but did not complement inability to induce E. coli SOS functions. The 395-amino acid DRT100 open reading frame encodes an apparent N-terminal chloroplast transit peptide and a putative 322 residue mature protein with a conserved nucleotide binding motif, but otherwise little global homology with bacterial RecA proteins. There are several tandemly repeated leucine-rich motifs. DNA from two closely related plants, but not from maize, hybridized strongly to a DRT100 cDNA probe. PMID- 1518833 TI - Molecular cloning and bacterial expression of cDNA encoding a plant cysteine synthase. AB - Cysteine synthase (CSase) [O-acetyl-L-serine acetate-lyase (adding hydrogen sulfide), EC 4.2.99.8] catalyzes the formation of L-cysteine, the key step in sulfur assimilation in plants, from O-acetyl-L-serine and hydrogen sulfide. We report here the isolation and characterization of cDNA clones encoding cysteine synthase from spinach (Spinacia oleracea L.). Internal peptide sequences were obtained from V8 protease-digested fragments of purified CSase. A lambda gt10 cDNA library was constructed from poly(A)+ RNA of young green leaves of spinach. Screening with two synthetic mixed nucleotides encoding the partial peptide sequences revealed 19 positively hybridized clones among 2 x 10(5) clones. Nucleotide sequence analysis of two independent cDNA clones revealed a continuous open reading frame encoding a polypeptide of 325 amino acids with a calculated molecular mass of 34,185 Da. Sequence comparison of the deduced amino acids revealed 53% identity with CSases of Escherichia coli and Salmonella typhimurium. Sequence homology was also observed with other metabolic enzymes for amino acids in bacteria and yeast and with rat hemoprotein H-450. A bacterial expression vector was constructed and could genetically complement an E. coli auxotroph that lacks CSases. The accumulation of functionally active spinach CSase in E. coli was also demonstrated by immunoblotting and assaying enzymatic activity. Southern hybridization analysis showed the presence of two to three copies of the cDNA sequence in the genome of spinach. RNA blot hybridization suggested constitutive expression in leaves and roots of spinach. PMID- 1518834 TI - Single crystal structure of a mixed-chain triacylglycerol: 1,2-dipalmitoyl-3 acetyl-sn-glycerol. AB - The mixed chain triacylglycerol 1,2-dipalmitoyl-3-acetyl-sn-glycerol was synthesized and its crystal structure was determined to a final reliability factor (R) of 0.11. Two molecules are present in the monoclinic unit cell: space group P2(1); a = 5.375(1), b = 8.286(2), c = 42.96(1) A; beta = 93.30(2) degrees, V = 1910 A3, rho = 1.065 g/cm3, and mu = 5.7 cm-1. The structure is a trilayer: a bilayer of palmitate chains packed in the beta mode (T parallel) and an interdigitated monolayer of acetates. The glycerol backbone and acetate extend roughly linearly from the sn-1 chain. The sn-2 chain bends around the C-2 carbon to lie next to the sn-1 chain. Analysis of the torsion angles indicate that the glycerol conformation of 1,2-dipalmitoyl-3-acetyl-sn-glycerol is markedly different from single acid triacylglycerols and from 1,2-diacyl-sn-glycerols but very similar to 1,2-dimyristoyl-sn-glycero-3-phosphocholine. PMID- 1518835 TI - Binding of the Drosophila transformer and transformer-2 proteins to the regulatory elements of doublesex primary transcript for sex-specific RNA processing. AB - Sex-specific alternative processing of double-sex (dsx) precursor messenger RNA (pre-mRNA) is one of the key steps that regulates somatic sexual differentiation in Drosophila melanogaster. By transfection analyses using dsx minigene constructs, we identified six copies of the 13-nucleotide sequences TC(T/A)(T/A)C(A/G)ATCAACA in the female-specific fourth exon that act as the cis elements for the female-specific splicing of dsx pre-mRNA. UV-crosslinking experiments revealed that both female-specific transformer (tra) and transformer 2 (tra-2) products bind to the 13-nucleotide sequences of dsx pre-mRNA. These results strongly suggest that the female-specific splicing of dsx pre-mRNA is activated by binding of these proteins to the 13-nucleotide sequences. PMID- 1518836 TI - Regulated expression of the human acetylated low density lipoprotein receptor gene and isolation of promoter sequences. AB - The acetylated low density lipoprotein (AcLDL) receptor is expressed on tissue macrophages after their differentiation from monocyte precursors and has been proposed to play a role in the generation of foam cells in atherosclerotic lesions. In the present studies, THP-1 human monocytic leukemia cells were used to investigate mechanisms responsible for expression of the AcLDL receptor gene after treatment with phorbol 12-myristate 13-acetate (TPA). TPA-dependent accumulation of AcLDL receptor mRNA was not detected until after a lag phase of 12 hr and was blocked by concurrent treatment with cycloheximide. In addition, the TPA-dependent induction of AcLDL receptor activity and mRNA levels was inhibited by retinoic acid and dexamethasone treatment. Isolation and sequence analysis of the promoter regions for the human and bovine AcLDL receptor genes indicated high sequence similarity. Binding sites for AP-1 proteins or other known transcription factors were not conserved between the two species, suggesting that novel factors are required for AcLDL receptor expression. PMID- 1518837 TI - Mutants of complement component C3 cleaved by the C4-specific C1-s protease. AB - To identify some of the structural features determining specific protease recognition of complement components C3 and C4, we used site-specific mutagenesis to construct mutants of murine C3 that are cleaved by the C4-specific C1-s protease. Insertion of three amino acid residues corresponding to residues at the C1-s cleavage site of human C4 into murine C3 at the analogous C3 convertase cleavage site was adequate to render the mutant protein susceptible to C1-s cleavage. In addition, insertion of C3-specific residues at the same site or introduction of the C4-specific residues as substitutions rather than as an insertion also rendered the site susceptible to cleavage, but with 10- to 50-fold lower efficiencies, and insertion of even a single amino acid residue affected recognition by C1-s. Finally, insertion of amino acid residues into mC3 partially inhibited cleavage by the alternative-pathway C3 convertase, with insertion of C3 or C4-specific residues giving about the same level of inhibition. A simple interpretation of these data is that C1-s cleavage is dependent primarily on steric accessibility and on recognition of specific amino acid residues at the cleavage site, whereas C3 convertase cleavage is dependent primarily on specific interactions distal to the cleavage site, with only relatively weak, non-C3 specific interactions at the cleavage site itself. PMID- 1518838 TI - Photosynthetic reaction center genes in green sulfur bacteria and in photosystem 1 are related. AB - Oxygenic photosynthesis of chloroplasts and cyanobacteria involves two photosystems, which originate from different prokaryotic ancestors. The reaction center of photo-system 2 (PS2) is related to the well-characterized reaction center of purple bacteria, while the reaction center of photosystem 1 (PS1) is related to the green sulfur bacteria, as is convincingly documented here. An operon encoding the P840 reaction center of Chlorobium limicola f.sp. thiosulfatophilum has been cloned and sequenced. It contains two structural genes, coding for proteins of 730 and 232 amino acids. The first protein resembles the large subunits of the PS1 reaction center. Putative binding elements for the primary donor, P840 in Chlorobium and P700 in PS1, and for the acceptors A0, A1, and FeS center X are conserved. The second protein is related to the PS1 subunit carrying the FeS centers A and B. An adjacent third gene, not belonging to the reaction center, encodes a protein related to dolichyl-phosphate D-mannose synthase from yeast. The different origins of PS1 and PS2 are discussed. PMID- 1518839 TI - The p50 subunit of NF-kappa B associates with the NF-IL6 transcription factor. AB - The NF-kappa B-p50 polypeptide, a member of the Rel family of transcription factors, was produced as a fusion protein containing amino-terminal peptide additions that facilitate purification and detection with a monoclonal antibody and specific radiolabeling by phosphorylation in vitro. The 32P-labeled NK-kappa B-p50 fusion polypeptide was used as the probe in Western blotting experiments and in screenings of a bacteriophage expression library to isolate cDNAs encoding interacting protein domains. As expected, cDNAs encoding proteins of the Rel family were identified. Surprisingly, the 32P-labeled NF-kappa B protein also specifically bound to proteins encoded by cDNAs for the human NF-IL6 transcription factor. The NF-kappa B-p50 and NF-IL6 proteins directly interact, and the Rel homology domain and leucine-zipper motif, respectively, are important for this interaction. Since induction of the NF-kappa B and NF-IL6 factors are important events in immune and acute-phase responses, this interaction could permit coregulation of genes. PMID- 1518840 TI - Glucose and glucosamine regulate growth factor gene expression in vascular smooth muscle cells. AB - We have investigated the regulation of the expression of two growth factors found in vascular smooth muscle, transforming growth factor alpha (TGF alpha) and basic fibroblast growth factor (bFGF). Cells cultured in medium containing 30 mM glucose exhibited a 2-fold increase in TGF alpha mRNA and a 3-fold increase in bFGF mRNA compared with cells grown in normal (5.5 mM) glucose. Glucosamine was more potent than glucose, leading to a 6-fold increase in TGF alpha mRNA. TGF alpha protein levels were also increased by glucosamine treatment, and the predominant species present was the membrane-bound precursor form of TGF alpha. To examine further the regulation of growth factors by sugars, cultured rat aortic smooth muscle cells were transfected with a plasmid construct consisting of a 1.2-kilobase-pair fragment of the TGF alpha promoter linked to a luciferase reporter gene. Increasing the concentration of glucose in the culture medium from 5.5 mM to 30 mM led to a rapid, 1.7-fold increase in the activity of the TGF alpha promoter. Glucosamine was much more potent than glucose in this stimulation, with 2 mM glucosamine causing a 12-fold increase in TGF alpha promoter activity. Insulin had no effect on luciferase activity in either the presence or the absence of added sugars. The glucose response element of the TGF alpha gene maps to a 130-base-pair segment that includes three potential binding sites for the transcription factor Sp1. We conclude that high glucose concentrations such as are reached in diabetes mellitus can stimulate the transcription of the genes for growth factors in vascular smooth muscle cells. This signaling pathway apparently involves the metabolism of glucose to glucosamine. This effect could be representative of nutritional regulation of a family of genes and could contribute to the toxicity of hyperglycemia and the vascular complications of diabetes. PMID- 1518841 TI - Identification, characterization, and localization of the dopamine D3 receptor in rat brain using 7-[3H]hydroxy-N,N-di-n-propyl-2-aminotetralin. AB - We have identified 7-[3H]hydroxy-N,N-di-n-propyl-2-aminotetralin ([3H]7-OH-DPAT) as a selective probe for the recently cloned dopamine D3 receptor and used it to assess the presence of this receptor and establish its distribution and properties in brain. In transfected Chinese hamster ovary (CHO) cells, it binds to D3 receptors with subnanomolar affinity, whereas its affinity is approximately 100-, 1000-, and 10,000-fold lower at D2, D4, and D1 receptors, respectively. Specific [3H]7-OH-DPAT binding sites, with a Kd of 0.8 nM and a pharmacology similar to those at reference D3 receptors of CHO cells, were identified in rat brain. D3 receptors differ from D2 receptors in brain by their lower abundance (2 orders of magnitude) and distribution, restricted to a few mainly phylogenetically ancient areas--e.g., paleostriatum and archicerebellum--as evidenced by membrane binding are autoradiography studies. Native D3 receptors in brain are characterized by an unusually high nanomolar affinity for dopamine and a low modulatory influence of guanyl nucleotides on agonist binding. These various features suggest that D3 receptors are involved in a peculiar mode of neurotransmission in a restricted subpopulation of dopamine neurons. PMID- 1518842 TI - Reversible structural alterations of undifferentiated and differentiated human neuroblastoma cells induced by phorbol ester. AB - Morphological alterations in the structure of undifferentiated and morphologically differentiated human neuroblastoma cells induced by phorbol 12 myristate 13-acetate (PMA), an activator of protein kinase C, were examined by video microscopy and immunomorphology. In undifferentiated cells, PMA induced the formation of motile actin-rich lamellas and of stable cylindrical processes rich in microtubules. Formation of stable processes resulted either from the collapse of lamellas or the movement of the cell body away from the base of a process. In differentiated cells, PMA induced the rapid extension of small lamellas and subsequent formation of short-lived elongated processes from the lateral edges of neurites. Additionally, growth cones exhibited enhanced modulation in shape after PMA treatment. These reversible reorganizations were similar to the actinoplast tubuloplast transformations exhibited by PMA-treated fibroblasts. We suggest that actinoplast-tubuloplast reorganizations play essential roles in morphogenesis where stable cytoplasmic extensions are induced by external stimuli. In particular, PMA-induced reorganizations of neural cells in culture may be a model for morphological modulations that occur in nerve tissue. PMID- 1518843 TI - Elimination of extrachromosomally amplified MYC genes from human tumor cells reduces their tumorigenicity. AB - Oncogene amplification has been observed in a broad spectrum of human tumors and has been associated with a poor prognosis for patients with several different types of malignancies. Importantly, at biopsy, the amplified genes localize to acentric extrachromosomal elements such as double-minute chromosomes (DMs) in the vast majority of cases. We show here that treatment of several human tumor cell lines with low concentrations of hydroxyurea accelerates the loss of their extrachromosomally amplified oncogenes. The decreases in MYC copy number in a human tumor cell line correlated with a dramatic reduction in cloning efficiency in soft agar and tumorigenicity in nude mice. No effect on gene copy number or tumorigenicity was observed for a closely related cell line containing the same number of chromosomally amplified MYC genes. One step involved in the accelerated loss of extrachromosomal elements is shown to involve their preferential entrapment of DMs within micronuclei. The data suggest that agents that accelerate the loss of extrachromosomally amplified genes could provide valuable tools for moderating the growth of a large number of human neoplasms. PMID- 1518844 TI - Thermodynamics of Cro protein-DNA interactions. AB - Using a highly sensitive pulsed-flow microcalorimeter, we have measured the changes in enthalpy and determined the thermodynamic parameters delta H, delta S degree, delta G degree, and delta C(p) for Cro protein-DNA association reactions. The reactions studied include sequence-nonspecific DNA association and sequence specific DNA associations involving single- and multiple-base alterations and/or single-amino acid alteration mutants. (i) The association of Cro protein with nonspecific DNA at 15 degrees C is characterized by delta H = +4.4 kcal.mol-1 (1 cal = 4.18J), delta S degrees = 49 cal.mol-1.K-1, delta G degrees = -9.7 kcal.mol 1, and delta Cp congruent to 0; the association with specific high-affinity operator OR3 DNA is characterized by delta H = +0.8 kcal.mol-1, delta S degree = 59 cal.mol-1.K-1, delta G degree = -16.1 kcal.mol-1, and delta Cp = -360 cal.mol 1.K-1, respectively. Both nonspecific and specific Cro-DNA associations are entropy-driven. (ii) Plots of delta H vs. delta Cp and delta S degree vs. delta Cp for the 20 association reactions studied fall into two correlation groups with linear slopes of +9.4 K and -20.5 K and of -0.03 and -0.14, respectively. These regression lines have common intercepts, at the delta H and delta S degree values of nonspecific association (where delta Cp congruent to 0). The results suggest that there are, at least, two distinct conformational subclasses in specific Cro DNA complexes, stabilized by different combinations of enthalpic and entropic contributions. The delta G degree and delta Cp values form an approximately single linear correlation group as a consequence of compensatory contributions from delta H and delta S degree to delta G degree and to delta Cp. Cro protein DNA associations share some similar thermodynamic properties with protein folding, but their overall energetics are quite different. Although the nonspecific complex is stabilized predominantly by electrostatic forces, it appears that H bonds, van der Waals contacts, hydrophobic effects, and charge interactions all contribute to the stability (delta G degree and delta Cp) of the specific complex. (iii) The variations in the values of the thermodynamic parameters are in general accord with our knowledge of the structure of the Cro DNA complex. PMID- 1518845 TI - X chromosome-linked Kallmann syndrome: stop mutations validate the candidate gene. AB - Kallmann syndrome represents the association of hypogonadotropic hypogonadism with anosmia. This syndrome is from a defect in the embryonic migratory pathway of gonadotropin-releasing hormone synthesizing neurons and olfactory axons. A candidate gene for the X chromosome-linked form of the syndrome was recently isolated by using a positional cloning strategy based on deletion mapping in the Xp22.3 region. With the PCR, two exons of this candidate gene were amplified on the genomic DNAs from 18 unrelated patients affected with the X chromosome-linked Kallmann syndrome. Three different base transitions--all leading to a stop codon- and one single-base deletion responsible for a frameshift were identified. We thus conclude that the candidate gene is the actual KAL gene responsible for the X chromosome-linked Kallmann syndrome. Furthermore, unilateral renal aplasia in two unrelated patients carrying a stop mutation indicates that the KAL gene is itself responsible for this Kallmann syndrome-associated anomaly. The gene is, therefore, also involved in kidney organogenesis. Additional neurologic symptoms in Kallmann patients are also discussed. PMID- 1518846 TI - Inhibited gastrulation in mouse embryos overexpressing the leukemia inhibitory factor. AB - Leukemia inhibitory factor (LIF) is a cytokine active in vitro on different target cells. It is detected in vivo during mouse gestation in both extraembryonic membranes and maternal tissues. Two isoforms have been described maintaining embryonic stem cells in culture in a pluripotent state. However, overexpression of their cDNAs in chimeric mouse embryos observed between 6.5 and 9.5 days postcoitus gave strikingly different phenotypes. Embryos overexpressing the diffusible form of LIF cDNA looked essentially normal. Chimerae expressing LIF associated with the extracellular matrix cDNA showed an abnormal proliferation of tissues and the absence of differentiated mesoderm. They have not undertaken the normal pathway of gastrulation. PMID- 1518847 TI - Phorbol ester stimulates a protein-tyrosine/threonine kinase that phosphorylates and activates the Erk-1 gene product. AB - The regulation of the Erk (extracellular-signal-regulated kinase) gene-encoded protein kinase activity by reversible phosphorylation has been reported to involve either an activator of autophosphorylation or an upstream protein kinase. In this communication we describe assays utilizing the Erk-1 protein fused to glutathione S-transferase that permit the identification of protein kinase(s) that phosphorylate and activate the myelin basic protein kinase activity encoded by the Erk-1 gene. A phorbol ester-stimulated protein kinase activity was identified that phosphorylated a kinase-negative Erk-1 gene product on tyrosine and threonine. The protein kinase phosphorylated and activated wild-type protein expressed in bacteria from 20- to 50-fold. The activation of the Erk-1-encoded myelin basic protein kinase required ATP and correlated directly with the degree of phosphorylation on the same amino acid residues previously shown to be phosphorylated in vivo. Conversion of the tyrosine site of phosphorylation to phenylalanine yielded an Erk-1 gene product that could not be activated. Similar results were obtained when the threonine site was mutated to valine. It is likely that the phorbol ester-stimulated protein-tyrosine/threonine kinase(s) is an up stream target for multiple extracellular signals. PMID- 1518848 TI - How reverse turns may mediate the formation of helical segments in proteins: an x ray model. AB - The three-dimensional structure of a protein is the assembly of different secondary structural elements, such as alpha-helices, beta-pleated sheets, and beta-turns. Although the conformation of hundreds of proteins has been elaborated in the solid state, only a vague understanding of the mechanism of their conformational folding is known. One facet of this topic is the conformational interconversion of one or more beta-turns to a helical structure (and vice versa), which may also be related to the formation of helix-turn-helix motifs often observed in globular proteins. Based on a comprehensive structural analysis of proteins, Sundaralingam and Sekharudu [Sundaralingam, M. & Sekharudu, Y. C. (1989) Science 244, 1333-1337] previously suggested that "structure-water" molecules in proteins may mediate such a conformational change. An x-ray crystal structure determination of t-butoxycarbonyl (Boc)-Val-Ser-NHCH3 reveals (i) an ideal type I beta-turn backbone conformation and (ii) a hydrogen-bond network more typical of an alpha-helix than a beta-turn conformation. The molecular packing of this simple beta-turn model reported here provides a plausible and simple alternative of how a beta-turn-like conformation may serve as a conformational template for helical-structure formation (and vice versa) during the folding procedure. PMID- 1518849 TI - Three human elastase-like genes coordinately expressed in the myelomonocyte lineage are organized as a single genetic locus on 19pter. AB - The human neutrophil and monocyte-derived serine protease homologues neutrophil elastase (NE), proteinase 3 (PR3), and azurocidin (AZU) are involved in a variety of immune defense reactions. NE and PR3 assist in the destruction of phagocytosed microorganisms, cleave the important connective-tissue protein elastin, and generate chemotactic activities by forming alpha 1-proteinase inhibitor complexes and elastin peptides. AZU is cytotoxic to certain microorganisms and chemotactic for monocytes. All three proteins are produced and packaged into azurophil granules in large quantities during neutrophil differentiation. We have isolated several cosmid clones each of which contains the functional genes for AZU, PR3, and NE in this order. The PR3 gene is separated by 8 kilobases from the 3' end of the AZU gene and by 3 kilobases from the 5' end of the NE gene. We report a physical map of the gene cluster, its location on chromosome 19pter, and the exon intron organization of the AZU and PR3 genes. Our fluorescence in situ hybridization studies disprove the previous chromosomal assignment of the human NE gene to 11q14. The five exons of AZU and PR3 are organized like those of NE and other granule-associated serine proteases of hematopoietic cells. NE, PR3, and AZU are coordinately downregulated in the premonocytic cell line U937 during induced terminal differentiation. The cluster-like physical organization of these genes and concerted regulation during hematopoietic differentiation suggests that they are located in a developmentally activated chromatin domain promoting high level, cell-specific expression in the monocyte-myelocyte lineage. PMID- 1518850 TI - Alloalbuminemia in Sweden: structural study and phenotypic distribution of nine albumin variants. AB - Plasma samples exhibiting alloalbuminemia on electrophoresis at pH 8.6 were requested from clinical laboratories throughout Sweden. Nine variants, each representing a different single point mutation, were found in 100 apparently unrelated Swedes. The overall prevalence of alloalbuminemia was estimated at 1:1700. Mutations were identified by protein-structural analysis followed by allele-specific DNA hybridization to verify the most common types. Slightly retarded (+1) mobility was seen in 80 cases. Of these, 71 had the Arg(-2)----Cys proalbumin variant previously called Malmo I proalbumin. Thirteen examples of the second most frequent type, the substitution Lys313----Asn and a mobility change of -1 charge unit, were found, as well as six cases of Glu570----Lys (albumin B) and a single case of Arg-1----Gln (proalbumin Christchurch). Five previously unreported types of alloalbuminemia were identified: four instances of Glu376--- Gln, which is the second known mutation at this site; two examples of Asp550--- Ala, the second mutation reported at this site; and one example each of Asp63--- Asn, Gln268----Arg, and Asn318----Lys. Other mutations were identified among eight subjects of foreign descent. The high frequency and relatively uniform geographic distribution of the Arg-2----Cys mutation suggest that it may have occurred in a founder individual many generation ago in Sweden. PMID- 1518851 TI - Molecular cloning of the cDNA for an MDCK cell Na(+)- and Cl(-)-dependent taurine transporter that is regulated by hypertonicity. AB - Cells in the hypertonic renal medulla maintain their intracellular ion concentration at isotonic levels, despite much higher concentrations of extracellular electrolytes, by accumulating high concentrations of nonperturbing small organic solutes termed osmolytes. Taurine has been identified as a nonperturbing osmolyte in the renal medulla and Madin-Darby canine kidney (MDCK) cells. In hypertonic medium, the increased accumulation of taurine in MDCK cells is the result of increased activity of a Na(+)- and Cl(-)-dependent taurine transporter. We have isolated a cDNA encoding a Na(+)- and Cl(-)-dependent taurine transporter, whose sequence corresponds to a protein of 655 amino acids with significant amino acid sequence similarity to previously cloned Na(+)- and Cl(-)-dependent transporters, including the MDCK cell betaine/gamma-aminobutyric acid transporter and several brain neurotransmitter transporters. Northern hybridization indicates that mRNA for the taurine transporter is present in renal cortex and medulla, ileal mucosa, brain, liver, and heart. The abundance of mRNA for the taurine transporter is increased in MDCK cells cultured in hypertonic medium, suggesting that regulation of transport activity by medium hypertonicity occurs at the level of mRNA accumulation. PMID- 1518852 TI - Leukemia inhibitory factor is expressed by the preimplantation uterus and selectively blocks primitive ectoderm formation in vitro. AB - Among its many activities, leukemia inhibitory factor (LIF) can maintain embryonic stem cell monolayers in a pluripotent undifferentiated state. Presuming that this might reflect its physiologic role during embryogenesis, we have examined LIF expression in the embryonic environment by RNase protection assays and have determined its in vitro effect on differentiating embryonic stem cell embryoid bodies. Of all adult tissues analyzed, LIF transcripts appear only in the uterus, where their level fluctuates with the estrous cycle, peaking after ovulation. LIF expression continues in the uteri of pregnant and pseudopregnant females, with a relative peak when blastocysts are normally present. As for its effects on in vitro differentiation, we have found that LIF blocks embryoid body differentiation only partially, yet in a precise manner. Using molecular markers to follow the differentiation of defined cell types, we demonstrate that LIF selectively inhibits the formation of primitive ectoderm, while permitting the differentiation of primitive endoderm. These results suggest a specific role for LIF in preimplantation mouse development. PMID- 1518853 TI - Delineation of the dystonia-parkinsonism syndrome locus in Xq13. AB - The X chromosome-linked dystonia-parkinsonism syndrome (XDP) is a severe movement disorder, characterized by both dystonia and parkinsonism. XDP is a genetically homogeneous disorder. Known ancestry of all patients has been traced back to Panay, Philippines, where the disease probably originated from a single mutation (founder effect). The gene locus, DYT3, has been previously assigned to the proximal long arm of the X chromosome (Xq12-q21.1). Using four dinucleotide tandem repeat (DNTR) sequences from Xq13-derived yeast artificial chromosomes (YACs), we further delineate DYT3 within Xq13. Observation of a recombination event between DYT3 and DNTR locus 4548-7, derived from a YAC encompassing locus DXS56, establishes 4548-7 as a distal flanking marker. Assignment of DYT3 to a region in Xq13, flanked by loci 4548-7 and DXS159, is further supported by highly significant allelic association between DYT3 and a total of four DNTR loci--PY2 31, PY5-10, 4548-1, and 4548-7--located in a region defined by PGK1 and DXS56. /phi/ and /delta/ values were 0.82/0.35, 0.78/0.42, 0.65/0.34, and 0.88/0.58 for PY2-31, PY5-10, 4548-1, and 4548-7 at P less than 10(-2), P less than 10(-4), P less than 10(-3), and P less than 10(-6). PMID- 1518854 TI - Cloning and expression of mouse integrin beta p(beta 7): a functional role in Peyer's patch-specific lymphocyte homing. AB - Lymphocytes express integrin receptors, termed lymphocyte Peyer's patch high endothelial venule (HEV) adhesion molecules (LPAMs), that mediate their organ specific adhesion to specialized HEVs found in mucosal lymphoid organs (Peyer's patches). LPAM-1 consists of a murine integrin alpha 4 noncovalently associated with integrin beta p. Here, we describe the cloning and expression of a mouse cDNA encoding beta p, which is an 806-amino acid transmembrane glycoprotein. The genomic Southern blot analysis indicates that beta p is the murine homologue of human beta 7. The function of alpha 4 beta 7 as a Peyer's patch-specific adhesion molecule was tested directly by expression of the murine beta 7 cDNA in an alpha 4+ beta 7-B-cell line or coexpression of the alpha 4 and beta 7 cDNAs in an alpha 4-beta 7-T-cell line. The transfected cells exhibited a new Peyer's patch specific adhesive phenotype that could be specifically blocked by monoclonal antibodies against alpha 4 and beta 7. Moreover, an anti-beta 7 monoclonal antibody specifically blocked binding of normal lymphocytes to Peyer's patch HEV but did not inhibit their binding to peripheral lymph node HEVs, indicating that beta 7 is a unique component of the Peyer's patch-specific homing receptor. PMID- 1518855 TI - Computer-assisted assignment of functional domains in the nonstructural polyprotein of hepatitis E virus: delineation of an additional group of positive strand RNA plant and animal viruses. AB - Computer-assisted comparison of the nonstructural polyprotein of hepatitis E virus (HEV) with proteins of other positive-strand RNA viruses allowed the identification of the following putative functional domains: (i) RNA-dependent RNA polymerase, (ii) RNA helicase, (iii) methyltransferase, (iv) a domain of unknown function ("X" domain) flanking the papain-like protease domains in the polyproteins of animal positive-strand RNA viruses, and (v) papain-like cysteine protease domain distantly related to the putative papain-like protease of rubella virus (RubV). Comparative analysis of the polymerase and helicase sequences of positive-strand RNA viruses belonging to the so-called "alpha-like" supergroup revealed grouping between HEV, RubV, and beet necrotic yellow vein virus (BNYVV), a plant furovirus. Two additional domains have been identified: one showed significant conservation between HEV, RubV, and BNYVV, and the other showed conservation specifically between HEV and RubV. The large nonstructural proteins of HEV, RubV, and BNYVV retained similar domain organization, with the exceptions of relocation of the putative protease domain in HEV as compared to RubV and the absence of the protease and X domains in BNYVV. These observations show that HEV, RubV, and BNYVV encompass partially conserved arrays of distinctive putative functional domains, suggesting that these viruses constitute a distinct monophyletic group within the alpha-like supergroup of positive-strand RNA viruses. PMID- 1518856 TI - Attenuation of GTPase activity of recombinant G(o) alpha by peptides representing sequence permutations of mastoparan. AB - There is convincing evidence that the cytoplasmic domains of multispanning receptors interact with guanine nucleotide-binding proteins (G proteins). What are the rules governing these interactions? In an attempt to answer this question, we focused our attention on mastoparan, an amphiphilic tetradecapeptide from wasp venom, and on nine of its variants, produced by sequence permutation, which have altered amphiphilicity or no amphiphilicity at all. Mastoparan enhances the GTPase activity of recombinant G(o) alpha 5-fold in phospholipid vesicles. Like mastoparan, four of the synthetic variants can form amphiphilic alpha-helices and two of them indeed stimulate the GTPase activity of the G protein, whereas the other two have no effect. This confirms that the activation of certain G proteins by a number of peptides is mainly due to their cationic amphiphilicity. However, this structural feature is clearly not sufficient. The relative orientation of the positively charged residues as well as that of the hydrophobic side chains appear to be of fundamental importance. The other five peptides are not amphiphilic and do not enhance the rate of GTP hydrolysis. Surprisingly, three of them almost completely inhibit the G protein's intrinsic GTPase activity. This finding is of interest because of the possible role differential regulation of G protein activity can play in cellular functions. PMID- 1518857 TI - Specific complex formation between proteins encoded by the yeast DNA repair and recombination genes RAD1 and RAD10. AB - The RAD1 and RAD10 genes of Saccharomyces cerevisiae are required for excision repair of ultraviolet light-damaged DNA, and they also function in a mitotic recombination pathway that is distinct from the double-strand-break recombination pathway controlled by RAD52. Here, we show that the RAD1 and RAD10 proteins are complexed with each other in vivo. Immunoprecipitation of yeast cell extracts with either anti-RAD1 antibody or anti-RAD10 antibody coprecipitated quantitative amounts of both RAD1 and RAD10 proteins. The level of coprecipitable RAD1 and RAD10 increased when both proteins were overproduced together, but not if only one of the proteins was overproduced. The RAD1/RAD10 complex is highly stable, being refractory to 1 M NaCl and to low concentrations of SDS. By hydroxylamine mutagenesis, we have identified a rad1 mutant allele whose encoded protein fails to complex with RAD10. The interaction-defective rad1 mutant resembles the rad1 or rad10 null mutant in defective DNA repair and recombination, implying that complex formation is essential for the expression of biological activities controlled by RAD1 and RAD10. PMID- 1518858 TI - Mechanism of C8 alkylation of guanine residues by activated arylamines: evidence for initial adduct formation at the N7 position. AB - Aromatic amines are bioactivated to electrophilic compounds that react with DNA, predominantly at the C8 position of guanine bases. This site is weakly nucleophilic and it has been proposed that the C8 adduct is the final product after initial N7-adduct formation. To consider this possibility, we reacted several C8-substituted guanine derivatives with N-acetoxy-2-aminofluorene, prepared in situ from 2-acetylsalicylic acid and N-hydroxy-2-aminofluorene. With C8,N9-dimethylguanine, an adduct was isolated in good yield that was consistent, by NMR and mass spectral characterization, with a structure involving carcinogen substitution at the N7 position of guanine and linked through the 2 aminofluorenyl nitrogen--N-(C8,N9- dimethylguanin-N7-yl)-2-aminofluorene. This adduct could be easily reduced with NaBH4, consistent with the proposed N7-adduct structure. The same reaction was also carried out with C8-methylguanosine and C8 methyldeoxyguanosine and similar adducts were isolated. In contrast, C8 bromoguanosine reacted with N-acetoxy-2-aminofluorene to yield the C8-substituted arylamine adduct N-(guanosin-C8-yl)-2-aminofluorene directly. These products are uniquely consistent with a scheme in which C8-adduct formation is preceded by an initial electrophilic substitution on the N7 atom, which is postulated to be a general reaction for activated arylamines and heterocyclic amines. PMID- 1518859 TI - Low activation barriers characterize intramolecular electron transfer in ascorbate oxidase. AB - Anaerobic reduction kinetics of the zucchini squash ascorbate oxidase (AO; L ascorbate:oxygen oxidoreductase, EC 1.10.3.3) by pulse radiolytically produced CO2- radical ions were investigated. Changes in the absorption bands of type 1 [Cu(II)] (610 nm) and type 3 [Cu(II)] (330 nm) were monitored over a range of reactant concentrations, pH, and temperature. The direct bimolecular reduction of type 1 [Cu(II)] [(1.2 +/- 0.2) x 10(9) M-1.s-1] was followed by its subsequent reoxidation in three distinct phases, all found to be unimolecular processes with the respective specific rates of 201 +/- 8, 20 +/- 4, and 2.3 +/- 0.2 s-1 at pH 5.5 and 298 K. While at this pH no direct bimolecular reduction was resolved in the 330-nm band, at pH 7.0 such a direct process was observed [(6.5 +/- 1.2) x 10(8) M-1.s-1]. In the same slower time domains where type 1 [Cu(I)] reoxidation was monitored, reduction of type 3 [Cu(II)] was observed, which was also concentration independent and with identical rate constants and amplitudes commensurate with those of type 1 [Cu(II)] reoxidation. These results show that after electron uptake by type 1 [Cu(II)], its reoxidation takes place by intramolecular electron transfer to type 3 [Cu(II)]. The observed specific rates are similar to values reported for the limiting-rate constants of AO reduction by excess substrate, suggesting that internal electron transfer is the rate determining step of AO activity. The temperature dependence of the intramolecular electron transfer rate constants was measured from 275 to 308 K at pH 5.5 and, from the Eyring plots, low activation enthalpies were calculated--namely, 9.1 +/- 1.1 and 6.8 +/- 1.0 kJ.mol-1 for the fastest and slowest phases, respectively. The activation entropies observed for these respective phases were -170 +/- 9 and -215 +/- 16 J.K-1.mol-1. The exceptionally low enthalpy barriers imply the involvement of highly optimized electron transfer pathways for internal electron transfer. PMID- 1518860 TI - Rudimentary form of cellular "vision". AB - BHK cells were inoculated sparsely on one face ("sparse- or s-face") of a thin glass film whose opposite face was covered with a 2- to 3-day-old confluent layer of BHK cells ("confluent- or c-face"). After 7 hr of attaching and spreading in the absence of visible light, most of the cells on the s-face traversed with their long axes the direction of the whorls of the confluent cells on the c-face directly opposed. The effect was inhibited by a thin metal coating of the glass films. The results suggest that the cells were able to detect the orientation of others by signals that penetrated glass but not thin metallic films and, therefore, appeared to be carried by electromagnetic radiation. In contrast, the effect was not influenced by a thin coat of silicone on the glass, suggesting that the wavelength of this radiation is likely to be in the red to infrared range. The ability of cells to detect the direction of others by electromagnetic signals points to a rudimentary form of cellular "vision." PMID- 1518861 TI - Retinoic acid-induced duplication of the zebrafish retina. AB - Exogenous treatment of zebrafish embryos with retinoic acid induces a duplication of the retinas during development. These effects occur only when retinoic acid is applied within a 2-hr period prior to and during the initial formation of the optic primordia, and they are concentration-dependent. Light microscopic examination reveals that the second retina derives from cells in the ventral region of the developing eyecup that normally become pigment epithelial cells. Two distinct ganglion cell fields are usually observed in eyes with duplicated retinas. Bundles of axons from each ganglion cell field join as they leave the eye and innervate the contralateral tectum. PMID- 1518862 TI - Induction of antigen-specific class I-restricted cytotoxic T cells by soluble proteins in vivo. AB - Cytotoxic T lymphocytes (CTL) are induced specifically against viral and tumor antigens presented by major histocompatibility complex class I molecules on the surface of infected or transformed cells. Intracellular synthesized antigens are processed and associated with class I antigens within cells before presentation on the cell surface. Because of this special requirement for CTL induction, exogenous soluble antigens do not, in general, induce specific CTL responses. To overcome this problem, various laboratories have resorted to the use of vaccinia virus and other replicating expression vectors for intracellular antigen delivery leading to the stimulation of humoral and cell-mediated immunity to specific proteins. However, for human use it is safer to use purified and defined antigens for inducing immune responses. Using soluble ovalbumin and human immunodeficiency virus glycoprotein gp120, we have explored the possibility of using an antigen formulation consisting of squalane and Tween 80 to elicit antigen-specific CTL responses in mice. We have demonstrated that this antigen formulation is a potent inducer of CD8+, class I-restricted, antigen-specific CTLs. The CTL priming induced by soluble antigen in squalane/Tween 80 resembles the reported response to the vaccinia recombinant containing human immunodeficiency virus envelope protein and by splenocytes cytoplasmically loaded with soluble ovalbumin. The ramifications of these findings for vaccine development are discussed. PMID- 1518863 TI - Tetrapeptide inhibitors of protein farnesyltransferase: amino-terminal substitution in phenylalanine-containing tetrapeptides restores farnesylation. AB - Protein farnesyltransferase from rat brain transfers farnesyl residues to cysteine residues in tetrapeptides that conform to the sequence CA1A2X, where C is cysteine, A1 and A2 are aliphatic amino acids, and X is methionine or serine. When the A2 residue is aromatic [e.g., phenylalanine as in Cys-Val-Phe-Met (CVFM)], the tetrapeptide continues to bind to the enzyme, but it can no longer accept a farnesyl group, and it becomes a pure inhibitor. The current studies show that this resistance to farnesylation also requires a positive charge on the cysteine amino group. Derivatization of this group with acetyl, octanoyl, or cholic acid residues or extension of the peptide with an additional amino acid restores the ability of phenylalanine-containing peptides to accept a farnesyl residue. The same result was obtained when the amino group of cysteine was deleted (mercaptopropionyl-VFM). These data suggest that the positive change on the cysteine amino group acts in concert with an aromatic residue in the A2 position to render peptides resistant to farnesylation by the rat brain enzyme. PMID- 1518865 TI - Tempo and mode of evolution revealed from molecular phylogenies. AB - The analysis of the tempo and mode of evolution has a strong tradition in paleontology. Recent advances in molecular phylogenetic reconstruction make it possible to complement this work by using data from extant species. PMID- 1518864 TI - Sequence analysis of rat mitochondrial intermediate peptidase: similarity to zinc metallopeptidases and to a putative yeast homologue. AB - Proteolytic removal of amino-terminal octapeptides from mitochondrial intermediate proteins is a required step for a subgroup of nuclear-encoded mitochondrial precursors and is specifically catalyzed by mitochondrial intermediate peptidase (MIP). We recently reported the purification of MIP from rat liver and showed that the enzyme is a monomer of 75 kDa. We now report the sequence of a full-length rat MIP cDNA. This cDNA codes for a protein of 710 amino acids, including an amino-terminal mitochondrial leader peptide of 33 residues. The region surrounding the mature MIP amino terminus shows a cleavage site typically recognized by the general mitochondrial processing peptidase (MPP). In vitro synthesized MIP precursor is cleaved to mature MIP by purified MPP, and thus MIP is not required for its own proteolytic maturation. Comparison of the deduced MIP sequence with other sequences in the GenBank data base reveals two important similarities. The first is to a sequence encoding a putative MIP homologue in the recently reported sequence of yeast chromosome III. The putative yeast protein is predicted to be 712 amino acids long and includes a putative 23 residue mitochondrial leader peptide also with a MPP processing site. It shows 47% similarity and 24% identity to rat MIP. The second similarity is to members of a subfamily of metallopeptidases that includes rat metalloendopeptidase EC 3.4.24.15 and two bacterial proteases, oligopeptidase A and dipeptidyl carboxypeptidase. A region of greater than 50% similarity over 400 residues between MIP and these proteins is centered around the sequence motif HEXXH, typical of zinc metallopeptidases. PMID- 1518866 TI - Glucocorticoid-suppressible hyperaldosteronism results from hybrid genes created by unequal crossovers between CYP11B1 and CYP11B2. AB - Glucocorticoid-suppressible hyperaldosteronism (GSH) is an autosomal dominant form of familial hypertension. The biochemical abnormalities seen in this disorder may be remedied by administration of dexamethasone, implying that aldosterone synthesis is being abnormally regulated by corticotropin. The final three steps of aldosterone synthesis, 11 beta- and 18-hydroxylation and 18 oxidation, are mediated by a cytochrome P450 in the zona glomerulosa of the adrenal cortex termed CYP11B2. A related isozyme in the zona fasciculata, CYP11B1, is required for cortisol synthesis; this isozyme, which is normally expressed at much higher levels than CYP11B2, only has 11 beta-hydroxylase activity. These isozymes are encoded by genes on human chromosome 8q22. We have now studied four unrelated patients with GSH. We found that each patient has one chromosome that carries three CYP11B genes instead of two. This has presumably been generated by unequal meiotic crossing-over. The extra gene is a hybrid with 5' regulatory and coding regions corresponding to CYP11B1 and 3' coding regions from CYP11B2. The breakpoint is in intron 2 in two cases, intron 3 in one, and exon 4 in one. Cells transfected with hybrid cDNAs containing up to the first three exons of CYP11B1 synthesized aldosterone at levels near that of cells carrying normal CYP11B2, but cells transfected with hybrids containing the first five or more exons of CYP11B1 could not synthesize detectable amounts of aldosterone. These data demonstrate that GSH is caused by expression of a gene that is regulated like CYP11B1 but that encodes a protein able to synthesize aldosterone. PMID- 1518867 TI - Induction of tolerance to an IgG autoantibody. AB - Nonautoimmune mice transgenic for the heavy chain of an IgG2b anti-double stranded-DNA antibody express the transgene in lymphoid organs and display partial allelic exclusion of this gamma 2b transgene. The spleens of these mice are characterized by marked B-cell depletion. Although there are B cells in these mice that express the transgene and recognize double-stranded DNA, they are anergic in vivo. Recovery from the state of anergy occurs in vitro after lipopolysaccharide stimulation. Thus this transgenic model demonstrates the induction of self tolerance to an IgG autoantibody. PMID- 1518868 TI - Serum proteases alter the antigenicity of peptides presented by class I major histocompatibility complex molecules. AB - Any effect of serum on the antigenicity of peptides is potentially relevant to their use as immunogens in vivo. Here we demonstrate that serum contains distinct proteases that can increase or decrease the antigenicity of peptides. By using a functional assay, we show that a serum component other than beta 2-microglobulin enhances the presentation of ovalbumin peptides produced by cyanogen bromide cleavage. Three features of this serum activity implicate proteolysis: it is temperature dependent, it results in increased antigenicity in a low molecular weight peptide fraction, and it is inhibited by the protease inhibitor leupeptin. Conversely, presentation of the synthetic peptide OVA-(257-264) is inhibited by serum. This inhibition is unaffected by leupeptin but is blocked by bestatin, a protease inhibitor with distinct substrate specificities. Implications for peptide-based vaccine design and immunotherapy are discussed. PMID- 1518869 TI - Sequence and expression of a membrane-associated C-type lectin that exhibits CD4 independent binding of human immunodeficiency virus envelope glycoprotein gp120. AB - The binding of the human immunodeficiency virus (HIV) envelope glycoprotein gp120 to the cell surface receptor CD4 has been considered a primary determinant of viral tropism. A number of cell types, however, can be infected by the virus, or bind gp120, in the absence of CD4 expression. Human placenta was identified as a tissue that binds gp120 in a CD4-independent manner. A placental cDNA library was screened by expression cloning and a cDNA (clone 11) encoding a gp120-binding protein unrelated to CD4 was isolated. The 1.3-kilobase cDNA predicts a protein of 404 amino acids with a calculated M(r) of 45,775 and organized into three domains: an N-terminal cytoplasmic and hydrophobic region, a set of seven complete and one incomplete tandem repeat, and a C-terminal domain with homology to C-type (calcium-dependent) lectins. A type II membrane orientation (N-terminal cytoplasmic) is predicted both by the cDNA sequence and by the reactivity of C terminal peptide-specific antiserum with the surface of clone 11 transfected cells. Native and recombinant gp120 and whole virus bind transfected cells. gp120 binding is high affinity (kd, 1.3-1.6 nM) and inhibited by mannan, D-mannose, and L-fucose; once bound, gp120 is internalized rapidly. Collectively, these data demonstrate that the gp120-binding protein is a membrane-associated mannose binding lectin. Proteins of this type may play an important role in the CD4 independent association of HIV with cells. PMID- 1518870 TI - Dynamic changes in receptive-field size in cat primary visual cortex. AB - Immediately after focal retinal lesions, receptive fields (RFs) in primary visual cortex expand considerably, even when the retinal damage is limited to the photoreceptor layer. The time course of these changes suggests that mere lack of stimulation in the vicinity of the RF accompanied by stimulation in the surrounding region causes the RF expansion. While recording from single cells in cat area 17, we simulated this pattern of stimulation with a pattern of moving lines in the visual field, masking out an area covering the RF of the recorded cell, thereby producing an "artificial scotoma." Over approximately 10 min this masking resulted in a 5-fold average expansion in RF area. Stimulating the RF center caused the field to collapse in size, returning to near its original extent; reconditioning with the masked stimulus led to RF reexpansion. Stimulation in the surrounding region was required for the RF expansion to occur- little expansion was seen during exposure to a blank screen. We propose that the expansion may account for visual illusions, such as perceptual fill-in of stabilized images and illusory contours and may constitute the prodrome of altered cortical topography after retinal lesions. These findings support the idea that even in adult animals RFs are dynamic, capable of being altered by the sensory context. PMID- 1518871 TI - Intrinsic signal optical imaging in the forepaw area of rat somatosensory cortex. AB - The responses of somatosensory cortex (S-I) to tactile stimulation of the forepaw were assessed by intrinsic signal optical imaging. The tips of digits two or five were alternately touched with mechanical tappers while video photographs were taken of S-I illuminated by an 800-nm light source. The resulting images showed two highlighted areas about 300 microns in diameter and 500 microns apart. Generation of these images required less than 1 hr. Electrode penetrations placed in the areas highlighted during stimulation provided multiunit recordings with receptive fields appropriate for the stimulated digit and not the other digit. Penetrations between the high-lighted areas yielded receptive fields on intervening digits. These results demonstrate that intrinsic signal optical images are obtainable in S-I and confirm the functional somatotopy previously reported using electrical recording. Furthermore, the short time required to produce the images and the obtainable spatial resolution suggest that optical recording could be employed for the study of cortical reorganization in this brain region. PMID- 1518872 TI - Abundant expression of parathyroid hormone-related protein in human amnion and its association with labor. AB - In animal models, parathyroid hormone-related protein (PTHrP) increases placental calcium transport and inhibits contraction of uterine smooth muscle. The present studies were undertaken to characterize the expression of PTHrP in human uteroplacental tissues. PTHrP mRNA was identified by Northern analysis as a single species (approximately 1.8 kilobases) in human amnion, chorion, placenta, decidua, and myometrium. The most abundant signal was seen in amnion, where it was 10-400 times that in the other uteroplacental tissues. PTHrP mRNA abundance was decreased in amnion (but not in the other tissues) following the onset of labor (P less than 0.001). PTHrP mRNA in amnion appeared to be translated to a bioactive peptide, as PTHrP bioactivity and immunoreactive PTHrP in amnion correlated closely with PTHrP mRNA content (r = 0.86 and 0.95, respectively; P less than 0.05 and P less than 0.01). Amniotic fluid contained PTHrP, 21 +/- 6 pmol/liter (n = 10) at 16 weeks and 41 +/- 9 pmol/liter (n = 7) at 38 weeks (P = 0.05). These concentrations equaled or exceeded those found in plasma of patients with hypercalcemia secondary to PTHrP. After rupture of the fetal membranes, PTHrP mRNA in amnion was decreased by 78% (P less than 0.0001). This decrease appeared to be specific for PTHrP mRNA, as glyceraldehyde-3-phosphate dehydrogenase mRNA was unchanged following rupture of membranes. Like PTHrP mRNA, PTHrP bioactivity and immunoreactive PTHrP in amnion decreased significantly following rupture of membranes (P less than 0.03 and P less than 0.01, respectively). Since PTHrP is a potent antagonist of uterine muscle contraction, the decrease of PTHrP following rupture of the fetal membranes may play a key role in the onset of labor. PMID- 1518874 TI - [Muscarinic receptor subtypes]. PMID- 1518875 TI - [Licorice products--unquestionably healthy? Some notes on the toxicology of glycyrrhizic acid]. PMID- 1518873 TI - Hierarchical analysis of linkage disequilibrium in Rhizobium populations: evidence for sex? AB - Many bacterial species exhibit strong linkage disequilibrium of their chromosomal genes, which apparently indicates restricted recombination between alleles at different loci. The extent to which restricted recombination reflects limited migration between geographically isolated populations versus infrequent mixis of genotypes within populations is more difficult to determine. We examined the genetic structure of Rhizobium leguminosarum biovar phaseoli populations associated with wild and cultivated beans (Phaseolus spp.) over several spatial scales, ranging from individual host plants to throughout the Western Hemisphere. We observed significant linkage disequilibrium at scales at least as small as a cultivated plot. However, the amount of disequilibrium was much greater among isolates collected throughout the Western Hemisphere than among isolates from one area of Mexico, even when disequilibrium was quantified using an index that scales for allelic diversity. This finding suggests that limited migration between populations contributes substantially to linkage disequilibrium in Rhizobium. We also compared the genetic structure for R. leguminosarum bv. phaseoli taken from a cultivated plot with that for Escherichia coli obtained from one human host in an earlier study. Even at this fine scale, linkage disequilibrium in E. coli was very near the theoretical maximum level, whereas it was much less extreme in the local population of Rhizobium. Thus, the genetic structure for R. leguminosarum bv. phaseoli does not exclude the possibility of frequent mixis within local populations. PMID- 1518876 TI - [Polysaccharides with antitumor activity from fungi]. PMID- 1518877 TI - [Ethylene-growth regulators and their possible use in plant cultivation]. PMID- 1518878 TI - [The biological actions of flavonoids. II]. PMID- 1518879 TI - 3,5-Bis-arylidene-1-methyl-4-piperidone methohalides and related compounds with activity against L 1210 cells and DNA binding properties. AB - A series of 3,5-bis-arylidene-1-methyl-4-piperidone methohalides 2 and two related analogues in general demonstrated activity against L 1210 leukemia cells in vitro and bound to a synthetic DNA, poly[d(AT)]. Plots of various physicochemical constants of the aromatic substituents in series 2 versus the IC50 figures revealed correlations between the aryl MR and pi values but not the sigma constants. The delta Tm values of six members of series 2 were correlated with the MR figures of the aryl substituents but not the sigma nor pi values of the aromatic atoms and groups. Some suggestions for future molecular modification with a view to increasing cytotoxicity are presented. PMID- 1518880 TI - Synthesis and pharmacology of 3-aryl-5,6-dihydro-6-oxo-1(4H)-pyridazineacetic acid derivatives. AB - The title compounds were prepared by alkylation of 6-aryl-4,5-dihydro-3(2H) pyridazinones with esters of alpha-bromoacetic acid. Hydrolysis of these esters afforded the corresponding carboxylic acids which were coupled with various amines yielding 6-oxo-1(4H)-pyridazineacetamides. A number of these derivatives showed weak anticonvulsant and weak analgesic activities, while nearly all displayed a sedative profile. PMID- 1518881 TI - Structure-activity relationship studies of CNS agents. Part 4: 2-[3-(4-aryl-1 piperazinyl)propyl]-1,2,3,4-tetrahydro-beta-carbolin+ ++ -1-one derivatives as potential central anti-serotonin agents. AB - Seven derivatives of 1,2,3,4-tetrahydro-beta-carbolin-1-one have been prepared. Three of them showed significant central anti-serotonin activity, comparable with that of trazodone or etoperidone. Some structural features were found to be important for the central antiserotonin activity of the investigated class of compounds. PMID- 1518882 TI - [Azoles. 34. Nitroimidazole derivatives and their antibacterial and fungicidal action]. AB - Nitroimidazole derivatives 4a-4c, 5a-5c, 8a-8c and 9a-9c were synthesized by treating 4,5-dinitro- and 2-methyl-4,5-dinitroimidazole (1,2) or their silver salts [1.Ag,, 2.Ag) with chlorosubtituted phenacyl bromides 3a-3c, diethyl sulphate or ethyl iodide, allyl iodide and ethyl chloro-, azo- or bromoacetate. 2,4(5)-dinitroimidazole (10) has been converted to the 2,4-dinitroimidazole derivative 10a by the action of ethyl bromoacetate in the presence of sodium ethylate. A modified method for the synthesis of 6a and 6b has been described. 7a and 7b have been obtained by a known method. Some of the newly synthesized nitroimidazole derivatives show antibacterial and fungicidal activity. PMID- 1518883 TI - Synthesis and antimicrobial activity of new 5-aryl-2-hydroxy-3(2H)-pyrrolinone derivatives. AB - The synthesis of some 1-substituted 5-aryl-2-hydroxy-2-methoxycarbonylmethyl 3(2H)-pyrrolinones is described. The results of microbiological screening are given. They indicate that 2-methylene-3(2H)-furanone and 2-hydroxy-3(2H) pyrrolinone derivatives exhibit a rather low antimicrobiological activity. PMID- 1518884 TI - Studies on dressings for dental surgery use. Part 3: Effect of gamma-radiation and of formaldehyde on properties of gelatinous dental dressings. AB - Gelatinous dressings were exposed to gamma-radiation or treated with formaldehyde to improve their resistance to the proteolytic effects of trypsin. After aging of the preparations, both gamma-irradiated and blank samples of gelatinous dressings were etched at a constant rate. Etching rate of the formaldehyde treated dressings decreases during storage. PMID- 1518885 TI - Investigations on the rectal absorption of chloramphenicol in rabbits after tenside use. AB - The rectal dose of 16 mg.kg-1 b.w. chloramphenicol (1) without additional tensides did not result in any detectable absorption of effective substance. In contrast, 0.04% of the N-lauroylleucine tenside allowed a rectal absorption having the same effect as that of an injection of the same quantities of effective substance. The tenside efficiency was not influenced by varied suppository masses (gelatine or Rosupol U, respectively), or by the pH value of the suppositories. Different particle sizes (less than 40 microns or greater than or equal to 40 up to less than 400 microns) of 1 did not change the absorption rate (AUC0-5h) significantly, but did change the plasma concentration-time profile considerably. PMID- 1518886 TI - Controlled-release tablet formulation of isoniazid. AB - Guar (GG) and Karaya gums (KG) alone and in combination with hydroxy propylmethylcellulose (HPMC) were evaluated as release retarding materials to formulate a controlled-release tablet dosage form of isoniazid (1). In vitro release of 1 from tablets followed non-Fickian release profile with rapid initial release. Urinary excretion studies in normal subjects showed steady-state levels of 1 for 13 h. In vitro and in vivo data correlated (r = 0.9794). The studies suggested the potentiality of GG and KG as release retarding materials in formulating controlled-release tablet dosage forms of 1. PMID- 1518887 TI - In vitro and in situ absorption of etamsylate. Part 2: In vitro and in situ properties. AB - The oil to water partition behaviour, the diffusion across artificial lipid barriers and the in situ gastro-intestinal absorption of the haemostatic etamsylate were studied. Very small partition coefficients were obtained (0.015 0.13) which are independent on the pH (range 1 to 6) and the nature of the organic phase (n-hexane, n-octanol, ethylacetate). Using the Sartorius membrane stimulator small diffusion constants were calculated both at phase I pH 6.0 (kd = 7.82.10(-3)cm.min-1) and especially at phase I pH 1.2 (kd = 4.7.10(-6) cm x min 1). The in situ absorption experiments on male Wistar rats showed very poor gastric absorption, but considerable intestinal absorption rate (absorption rate constant ka = 0.39 +/- 0.19 h-1, absorption half life t1/2(ka) = 1.94 +/- 0.60 h). The ion-pair diffusion across the intestinal wall seems to be the main reason responsible for the fast intestinal absorption. The obtained results are consistent to the literature data concerning etamsylate pharmacokinetics in vivo. PMID- 1518888 TI - Antitumor activity of patulin and structural analogs. AB - A comparison between the cytotoxicity and the antitumor activity of patulin and five structural analogs (isopatulin, dehydroisopatulin, dimethylisopatulin, trimethylisopatulin and isopropylisopatulin) has been established. In vitro assays using L 1210 and P 388 cells showed that the structure of the pyranic ring as well as the nature of the substituents influenced the observed activities. Among the five structural analogs of patulin assayed in vivo against Ehrlich carcinoma, L 1210 and P 388 leukemias, dehydroisopatulin was the only one to be active on all 3 types of tumors at a dose of 100 mg.kg-1.d-1. The ratio between the LD50 in mice and the active dose was 5 while with patulin it was 10. It can be assumed that the lactone function is not solely responsible for the activity of patulin and its structural analogs. PMID- 1518889 TI - Synthesis and biological evaluation of some new phosphonates. PMID- 1518890 TI - Synthesis and mass spectra of some thiazole aminoketones with prospective local anaesthetic activity. PMID- 1518891 TI - [2-Amino-oxazoles as potential H-bonding agents in virostatic research. 3. Synthesis, substance characterization and antiviral action of 2-guanidino-4,5 dipropyl-oxazole hydrochloride]. PMID- 1518892 TI - The antimicrobic effect of berberine and tinctura berberidis. PMID- 1518893 TI - Synthesis of isothiazole derivatives with potential biological activity. AB - The synthesis of acyl and ureido derivatives of substituted amides of 3-methyl-5 aminoisothiazole-4-carboxylic acid is presented. The structures of the compounds obtained were established on the basis of IR, 1H NMR and elemental analysis. The influence on the circulatory system of the derivatives was investigated. All structures of the compounds obtained were fully confirmed by IR and 1H NMR as well as by elemental analysis (Table). PMID- 1518894 TI - Studies on azopyrazole derivatives. Part 9: Synthesis and antibacterial evaluation of novel phenylhydrazones and their substituted 4-arylazopyrazole derivatives. AB - 6-Methyl-2,4-heptandione (1) was coupled with diazonium salts of sulfanilamide (2) and 4-aminobenzoic acid (3). Resulting new hydrazones, namely 4-methyl-2 oxovaleraldehyde p-substituted phenylhydrazones 4 and 5, were refluxed with various hydrazines to synthesize the title compounds 6-15. Their structure elucidation was made on the basis of their analytical and spectroscopic data. The antibacterial activity was evaluated. Some of the compounds tested exerted moderate to potent antibacterial activity against Staphylococcus aureus, Staphylococcus epidermidis and Streptococcus pyogenes. PMID- 1518895 TI - Evaluation of nifedipine preparations by chromatographic-spectrophotometric methods. AB - The content of nifedipine in 10 currently available preparations (tablets, capsules, dragees and drops) was analyzed. In the qualitative analysis, a TLC method was employed, whereas in the quantitative analysis, a chromatographic spectrophotometric method developed in our laboratory (TLC-UV), a TLC-UV method according to USP XXI, and the method of gas chromatography coupled with mass spectrometry (GC-MS) were employed. For all the preparations under study, the presence of at least one decomposition product as well as a decrease in the content of active component, in most cases proportional to the storage time, were observed. However, in none of the preparations pyridine nitro derivative decomposition products were found, but in each the presence of nitroso derivative was reported. As a result, it was stated that about a half of the preparations studied do not meet the requirements of USP XXI as for as the content of the active substance is concerned, which suggests that the expiration date is shorter by 6 to 12 months. PMID- 1518896 TI - [Mucus models for investigation of intestinal absorption mechanisms. 1. Validation and optimization of the model]. PMID- 1518897 TI - Bioavailability of metronidazole formulations (Vagimid). AB - The bioavailability of metronidazole (0.5 g) from Vagimid tablets and dragees were compared with tablets of a reference formulation in 12 male healthy volunteers (age 20-32 years, body weight 61-77 kg). Metronidazole and its two main oxidized metabolites in serum were determined quantitatively with an hplc method. Metronidazole from Vagimid tablets was absorbed more rapidly than from the reference but at the same extent of absorption. The pharmacokinetic profile of Vagimid dragees was similar to the behaviour of the reference but AUC of dragees was slightly but significantly lower. All elimination parameters of metronidazole as well as the formation of the two metabolites were not different after administration of the oral formulations. PMID- 1518898 TI - Pharmacodynamic interactions between isoniazid and theophylline in mice and rats, and the influence of pyridoxine. AB - Convulsions induced by acute administration of isoniazid (1), theophylline (2) as well as combinations of 1 and 2 were evaluated in male albino mice and male Wistar rats. The effect of pyridoxine (3) on these seizures was tested. Serum and brain levels of 1 after coadministration with 2 and caffeine (4) were assessed. The relevance of the observed pharmacokinetic phenomena in serum is questionable for the CNS processes because animals convulsed late (starting 90 min) and no significant changes of brain levels of 1 were observed. In conclusion, interactions of 1 and 2 may not occur through common mechanisms and exist only if the dose of 1 is toxic suggesting toxicological rather than therapeutic relevance. PMID- 1518899 TI - [Relationship between chemical structure and toxicologic-pharmacokinetic properties of new ampicillin derivatives]. AB - The toxicity and the bioavailability of new ampicillin derivatives with glyoxylic acid benzhydrazones as site chain depend on the hydrophobic properties of the site chain. Substituents with lower hydrophobicity (expressed by the hydrophobic substituent constant pi according to Hansch) show a lower toxicity (maximal tolerated doses) and also a lower bioavailability. PMID- 1518900 TI - [The yeast test: an alternative method for determination of acute toxicity of drugs and environmental chemicals]. AB - Starting point for this study was the urgent need for replacement of the contemporary mode of acute toxicity testing of chemicals in vertebrates (LD50 test) by an experimental model with equal power that can be performed on non-pain sensitive matter. For this purpose, a testing procedure ought to be developed using a non-pathogenic microorganism as testing object that is available at any time, easy to cultivate, and in its indicative power equivalent to the LD50 test in mice, rats, and other laboratory animals. Such an organism has been found with ordinary yeast (baker's yeast, brewer's yeast, Saccharomyces cerevisiae) which can always be obtained in good quality. This procedure (shortly denominated as 'yeast test' offers several advantages: It is rather simple, inexpensive, outstandingly well reproducible, and it can be carried out conveniently also in routine experiments. The results correlate well with those furnished by the customary methods of acute toxicity testing. PMID- 1518901 TI - [The influence of pharmacists on the development of pharmacy and chemistry as diciplines]. AB - The aim of this article is to trace some features of the historical development of chemistry as an academic discipline in its relation to the emergence of pharmaceutical science. Franz Joel (1508-1579) was one of the first pharmacists whose work became very important for development of chemistry since the 17th century lectures in materia medica and in iatro-chemistry were frequent realized in university pharmacy. In the 18th century pharmacists were in some cases the precursors to professors of chemistry. In the paper there is also given a summary of the importance for the development of chemistry of J. B. Trommsdorff, S. F. Hermbstaedt, A. P. J. Du Menil and L. F. Bley. PMID- 1518902 TI - [Computer simulation of blood level profiles. Drug liberation from two sustained release preparations and computer simulation of single- and multiple-dose pharmacokinetics]. AB - A series of computer programs (BASIC) is introduced for the evaluation of in vitro dissolution data as well as for the calculation of pharmacokinetic parameters and for blood level curve fitting to the respective in vitro data. Furthermore, programs are offered for the simulation of blood level profiles under variable conditions. In order to demonstrate the practical use of these programs, the expected blood level profiles following the administration of two commercial sustained-release dosage forms containing the drug pentoxifylline have been compared. PMID- 1518903 TI - Comparison of HPLC and derivative spectrophotometric method of the determination of paracetamol (acetaminophen) and acetylsalicylic acid in tablets. PMID- 1518904 TI - Spatial resolution and count density requirements in brain SPECT imaging. AB - A set of simulations has been performed to investigate the spatial resolution and count density requirements for brain SPECT imaging. Projections were drawn from a matrix representation of the Hoffman brain phantom. These projections were convolved with realistic point spread functions and Poisson noise was added to simulate a wide range of imaging situations normalized to a fixed imaging time. The projections were optimally smoothed with a Wiener filter and were reconstructed with a ramp filter. The quality of the reconstructed images was determined objectively from the normalized mean square between the simulated data and the true distribution. This ranking was validated against the preferences of a group of trained observers. The results from this study indicate that the optimal choice of spatial resolution (collimation) depends on the available count density. As the count density (normalized to 10 mm resolution) increases by a factor of 2.7, results from the simulations indicate that the optimal spatial resolution improves by 1 mm. For brain studies in which the administered activity is limited (such as 123I IMP), the optimal spatial resolution is approximately 8 to 9 mm. With 99Tcm labelled brain agents the amount of administered radioactivity can be increased six-fold and the optimal spatial resolution is predicted to fall to about 6 to 7 mm. If sensitivity is further increased by the use of a dedicated SPECT unit with multiple detectors, the optimal spatial resolution will be on the order of 4 to 5 mm. PMID- 1518905 TI - Physical performance of a positron tomograph for brain imaging with retractable septa. AB - Performance characteristics of a new design of positron tomograph with automatically retractable septa for brain imaging have been studied. The device, consisting of block BGO detectors (8 x 8 elements per block), has a ring diameter of 76 cm and an axial FOV of 106.5 mm. The in-plane resolution is on average 5.8 mm and 5.0 mm (FWHM) for stationary and wobble sampling, respectively, over the central 18 cm of the transaxial FOV. Its unique feature is the capability of data acquisition both in the 'conventional' 2D mode (with septa) or 3D mode (septa retracted) where coincidences between any of the 16 detector rings are acquired. When scattered events are subtracted, the efficiency for a 20 cm diameter uniform cylinder increases overall by a factor of 4.8 between 2D (septa extended) and 3D modes. For a 20 cm phantom the trues/singles ratio is higher for 3D than for 2D but for a given unscattered trues rate, the randoms rate in 3D is higher. At 380 keV the scatter fraction within a 20 cm cylinder is 10% (septa extended) and 36% (retracted). In spite of the increase in scatter when septa are retracted, the increased efficiency in the 3D mode of acquisition yields distinct advantages, particularly in the many studies where tracer concentration is low and consequently where dead time and random rates are less important. PMID- 1518906 TI - Design studies related to an in vivo neutron activation analysis facility for measuring total body nitrogen. AB - Design studies relating to an in vivo prompt capture neutron activation analysis facility measuring total body nitrogen are presented. The basis of the design is a beryllium-graphite neutron collimator and reflector configuration for (alpha, n) type radionuclide neutron sources (238PuBe or 241AmBe), so as to reflect leaking, or out-scattered, neutrons towards the subject. This improves the ratio of thermal neutron flux to dose and the spatial distribution of thermal flux achieved with these sources, whilst retaining their advantage of long half-lives as compared to 252Cf based systems. The common problem of high count-rate at the detector, and therefore high nitrogen region of interest background due to pile up, is decreased by using a set of smaller (5.1 cm diameter x 10.2 cm long) NaI(Tl) detectors instead of large ones. The facility described presents a relative error of nitrogen measurement of 3.6% and a nitrogen to background ratio of 2.3 for 0.45 mSv skin dose (assuming ten 5.1 cm x 10.2 cm NaI(Tl) detectors). PMID- 1518907 TI - Dielectric properties of biological tissue at low temperatures demonstrated on fatty tissue. AB - Dielectric behaviour of fatty tissue was investigated from T = 300 K to 4 K and f = 20 Hz to 1 MHz. Characteristic curves were obtained only at low frequencies. With decreasing temperature four important features were detected: the water-ice transition at T = 265 K, a relaxation process of the fat molecules (near 260 K) and one connected with the ice-part (210 K-170 K). The reason for the fourth relaxation at T = 140 K has not been fully understood yet: it may be caused by segmental rotation of the fatty acid molecules or the presence of multiple bonds. The epsilon"-maximum caused by the ice relaxation at T congruent to 200 K can be used to detect successful application of cryotherapy, i.e. the temperature fall below the minimum value of 233 K. PMID- 1518908 TI - Optimization by simulated annealing of three-dimensional, conformal treatment planning for radiation fields defined by a multileaf collimator: II. Inclusion of two-dimensional modulation of the x-ray intensity. AB - Interest is rapidly growing in using multiple x-radiation fields defined by a multileaf collimator to achieve conformal radiotherapy. Three-dimensional treatment planning in such situations is in its infancy and most 3D planning systems provide no tools for optimizing therapy. A previous paper addressed how to calculate optimum beamweights when both the target volume and all or some parts of organs at risk were in the fields-of-view. This work allowed a maximum of two weights per field. The present paper extends this technique to allow each radiation port to be spatially modulated across the geometrically shaped field. An optimization method based on simulated annealing is presented. It is shown that including spatial modulation leads to a wider separation between the dose volume histograms of the target volume and organs at risk. The improvement is quantified in terms of the tumour control probability at constant normal tissue complication probability. Possible limitations of the a posteriori applied biological model are discussed in detail. PMID- 1518909 TI - Physical characterization of the replication origin of the cryptic plasmid pCB101 isolated from Clostridium butyricum NCIB 7423. AB - The complete nucleotide sequence of a 3484-bp Sau3A fragment, previously shown to carry the replication origin of the Clostridium butyricum NCIB 7423 plasmid pCB101 (6.05 kb), has been determined. Of the four open reading frames (ORF A-D) identified within this fragment, two (B and C) were shown to be encoding by in vitro transcription/translation assays. Evidence was obtained that both polypeptides are required for autonomous replication of the plasmid in Bacillus subtilis. ORF C is immediately preceded by a small ORF (C') that encodes a relatively small polypeptide (50 amino acids) that demonstrates significant homology with RepA of plasmid pLS1. Whereas the ORF C polypeptide (27,100 Da) exhibits no homology to any known protein, that encoded by ORF B (RepB, 43,039 Da) exhibits significant homology with the Rep proteins of the pC194/pUB110 subfamily of single-strand (ss) DNA plasmids, which are widely distributed in gram-positive bacteria. Conserved amino acids include the presumed active site of topoisomerase activity and four cysteine residues in the N-terminus of all Rep proteins compared. The repB gene is preceded by a sequence motif exhibiting substantial homology to the "plus" origins of this family of ss DNA plasmids and was shown to act as a "hot spot" for deletion formation in certain plasmid chimaeras. The compelling suggestion that pCB101 replicates via a rolling circle mechanism was substantiated by the demonstration of ss DNA replication intermediates in B. subtilis cells carrying a pCB101-derived plasmid. PMID- 1518910 TI - Construction and characterization of shuttle plasmids for lactic acid bacteria and Escherichia coli. AB - The chimeric plasmid pBN183 was first constructed in Escherichia coli by ligating the BamHI-digested E. coli plasmid pBR322 and a Bg/II-linearized streptococcal plasmid, pNZ18. The pBN183 transformed E. coli to ApR at a frequency of (8.2 +/- 1.2) x 10(5) colony forming units (CFU)/microgram DNA. Electrotransformation of Streptococcus thermophilus with pBN183 yielded CmR, ApS clones at a frequency of (2.6 +/- 0.3) x 10(1) CFU/microgram DNA. Plasmid screening with pBN183 transformed S. thermophilus clones revealed that ca. 70% of these transformants contained deleted plasmids. Plasmid pBN183A, a pBN183 deletion mutant lacking one copy of a tandemly arranged, highly homologous DNA sequence, was isolated for further study. It transformed E. coli to ApR and S. thermophilus to CmR with frequencies of (4.8 +/- 0.1) x 10(5) and (8.1 +/- 0.2) x 10(2) CFU/microgram DNA, respectively. Screening of S. thermophilus transformants did not show the presence of deleted plasmids. Based on the structure of pBN183A, a new shuttle plasmid, pDBN183, was constructed from pBN183 by removal of the small (1.2 kb) Sa/I fragment. Transformation frequencies of pDBN183 were (5.0 +/- 1.3) x 10(5) and (4.6 +/- 0.2) x 10(2) CFU/microgram DNA with E. coli and S. thermophilus, respectively. In contrast to the parent pBN183, only 17% of the pDBN183 transformed S. thermophilus contained deleted plasmids. Plasmid copy numbers of the three vectors in E. coli were estimated at 17-18 per chromosome. The three plasmids conferred ApR and CmR to E. coli, but only CmR to S. thermophilus. The insertion of a Streptomyces cholesterol oxidase gene (choA) into pDBN183 did not affect the plasmid's stability in Lactobacillus casei, but resulted in deletion of the recombinant DNA in S. thermophilus. PMID- 1518911 TI - Dictyostelium giganteum plasmid Dgp1 is a member of the Ddp2 plasmid family. AB - Dgp1, a circular 4.4-kb plasmid found in the nuclei of Dictyostelium giganteum strain DG61, is a member of the same plasmid family as plasmids Ddp2 and pDG1. Dgp1 has sequence similarity to a conserved region of the Ddp2 and pDG1 open reading frames. As with Ddp2 and pDG1, a single large RNA is transcribed from Dgp1. This 3.3-kb transcript is present at about 350 copies per vegetative cell. The transcript abundance decreased about 10-fold in early aggregation and continued at this lower level until late culmination when it returned to the level seen in vegetative cells. Dgp1 has a repeat of several hundred base pairs in a location, relative to the transcribed region, similar to the inverted repeats found in Ddp2 and pDG1. Dgp1 cannot be maintained as a plasmid in Dictyostelium discoideum AX4 cells, suggesting that Dgp1 carries species-specific maintenance elements. PMID- 1518912 TI - Selection of Dictyostelium discoideum transformants and analysis of vector maintenance using live bacteria resistant to G418. AB - A protocol that allows the rapid isolation and growth of large numbers of independent G418-resistant Dictyostelium discoideum transformant colonies on the surface of agar media with live bacteria was developed. Transformants grown under these conditions form normal fruiting bodies. Discovery that aggregation of nontransformants was inhibited at a nonselective level of G418 (25 to 35 micrograms/ml) led to the development of a vector maintenance assay. Using this assay we examined the stability of recombinant plasmids derived from the D. discoideum native plasmids Ddp1 and Ddp2. We conclude that the origin of replication of plasmid Ddp1 does not alone confer stable maintenance and thus, Ddp1 must bear additional sequences required for its own maintenance. Analysis of the maintenance of vectors derived from Ddp2 showed that autonomously replicating shuttle vectors that contained bacterial plasmid DNA and from which one element of the Ddp2 inverted repeat was removed were much less stable than vectors that contained a complete inverted repeat or that did not carry a bacterial plasmid. Sequences between the 3' end of the rep gene and the inverted repeat appear to play a role in plasmid maintenance. An intact rep gene and one copy of the inverted repeat element were required for extrachromosomal replication. Maintenance of extrachromosomal vectors was found to be strain dependent. Four traits distinguishing integrating vectors from those capable of autonomous replication were identified. PMID- 1518913 TI - Transfer of a plasmid determining bacteriocin Bc-48 production and immunity, and response to sexual pheromones in Enterococcus faecalis S-48. AB - Production of bacteriocin Bc-48 by Enterococcus faecalis S-48 is encoded by the conjugative plasmid pMB1, which is approximately 90 kb and also responds to sex pheromones of E. faecalis OG1X. Mutants harboring deleted forms of this plasmid (pMB1-del, 75 kb) have lost both the phenotype Bc-48 (production and immunity) and the clumping response. The conjugal transfer of pMB1 to E. faecalis OG1X results in the acquisition by this strain of both bacteriocin production and immunity and also the clumping response. In the transconjugants isolated, the bacteriocinogenic trait is associated with a smaller plasmid (52 kb), which we call pMB1-1. The relationship among plasmids pMB1, pMB1-del, and pMB1-1 has been demonstrated by DNA hybridization. Plasmid pMB1-1 has been transferred with high frequency to E. faecalis mutants cured of Bc-48 production (carrying pMB1-del), conferring to them the Bc-48 trait and clumping response. In the transconjugants from a second mating, pMB1-1 and pMB1-del coexist without appreciable segregation. PMID- 1518914 TI - Plasmid pTB913 derivatives are segregationally stable in Bacillus subtilis at elevated temperatures. AB - We studied the effects of temperature on the segregational stability of derivatives of the rolling-circle-type plasmid pTB913 in Bacillus subtilis. This 4.5-kb plasmid is a deletion derivative of pTB19, which was originally isolated from a thermophilic Bacillus. pTB913 derivatives carrying large inserts or lacking the minus origin for complementary strand synthesis were segregationally unstable at 37 degrees C. In contrast, at 47 degrees C all pTB913 derivatives tested were stably maintained in B. subtilis. The increased stability at 47 degrees C was attributed, at least partly, to increased copy numbers at this temperature. Although considerable amounts of single-stranded and high-molecular weight plasmid DNA were formed at 47 degrees C, these products did not reduce plasmid stability at this temperature. The increased stability and increased copy number of pTB913 at elevated temperatures extend the use of this plasmid as a cloning vector in B. subtilis and other bacilli. PMID- 1518915 TI - Nucleotide sequence of Mycoplasma mycoides subspecies Mycoides plasmid pKMK1. AB - To facilitate the development of mycoplasmal cloning vectors, we have determined the nucleotide sequence of pKMK1, a cryptic plasmid isolated from Mycoplasma mycoides subsp. mycoides. It is 1875 bp in length and contains two open reading frames (ORFs) that share homology with ORFs from members of a large family of gram-positive bacterial plasmids which replicate via a single-stranded DNA intermediate. Putative origins of replication and candidate cloning sites have been identified. PMID- 1518916 TI - The environment and population growth: decade for action. AB - The signs of environmental stress grow as the world's population increases: worn out farmlands, eroded hillsides, polluted water, parched grasslands, smoke-laden air, depleted ozone, and treeless ranges. Each year about 17 million hectares of tropical forest vanish--an area the size of Tunisia or Uruguay. Fish catches are leveling off. Cities are clogged with refuse. Water and air, instead of sustaining life, cause disease. PMID- 1518917 TI - Self-rated inhibited anger, somatization and depression. AB - In order to examine the relationship of self-rated inhibited anger to somatization, the authors administered several self-rating scales, including the SCL-90 and a Likert scale pertaining to inhibited anger, to psychiatric patients and family practice patients of both sexes. In a linear stepwise regression, depression predicted inhibited anger in all four groups. Previous studies have reported an association of inhibited anger and somatization; the present study suggests that depression is the link between the two in the majority of patients. The relationship of inhibited anger to depression may have implications for psychotherapy. PMID- 1518918 TI - Critical life changes. A review of research. AB - This review of ideas presented in life event research presents a psychological and a sociological research tradition. Physiological recordings of endocrine factors have been utilized in studies of life events both in the study of natural course (bereavement and accidents, for instance) and in the laboratory during talk about critical life events. Recently, several programmes have been started for improving people's life event tolerance. However, 'eventlessness' has also been observed to be a possible disease-provoking factor. PMID- 1518919 TI - Psychological reactions to medical procedures. AB - Many medical procedures evoke anxiety and discomfort. Despite substantial research effort showing the efficacy of psychological interventions, there is abundant evidence that patients remain inadequately prepared. This review of well tried approaches demonstrates that varied interventions are required to reduce stress and discomfort and outlines ways in which staff should apply the research findings. PMID- 1518920 TI - Hyperprolactinaemia as a result of immaturity or regression: the concept of maternal subroutine. A new model of psychoendocrine interactions. AB - Pathological hyperprolactinaemia (PH) is significantly associated with: (1) paternal deprivation during childhood, (2) depression, (3) non-specific symptoms including obesity and weight gain. The clinical onset of the symptoms often follows pregnancy or a loss. Prolactin is an insulin antagonist which does not promote weight gain. Hyperprolactinaemia and increased metabolic efficiency are parts of a system of interdependent behavioural and metabolic mechanisms necessary for the care of the young. We call this system, which is available as a whole package, maternal subroutine (MS). An important number of cases of PH are due to activation of the MS that is not induced by pregnancy. The same occurs in surrogate maternity and in some animal models. Most women with PH developed a malignant symbiotic relationship with their mothers in the setting of absence, alcoholism or devaluation of the father. These women may regress to early developmental stages to the point that they identify themselves both with their lactating mother and with the nursing infant as has been found in psychoanalysed patients and in the paradigmatic condition of pseudopregnancy. Such regression can be associated with activation of the MS. Prolactinomas represent the extreme of the spectrum of PH and may result from somatic mutations occurring in hyperstimulated lactotrophs. PMID- 1518921 TI - The training of the psychiatrist in relation to the new trends in psychiatry. AB - One of the most important things to realize about modern Psychiatry is that many factors are involved in the pathogenesis and especially in the evolution of mental diseases. The results of epidemiological research and the development of different schools with separate specializations have shown the importance of extrasubjective factors such as family environment, social context, life events and life stressors, and therefore the need to find therapeutic strategies which are able to influence the different areas. From this wide spectrum arises the necessity for a functional integration of the different therapeutic areas in the operative context, also because of the nonhomogeneity and the frequent random choice of reference models by the operators and the mental health services. In this study we propose a training model which allows the achievement of this integration ability at an operative level, and which at the same time defines its limits. PMID- 1518922 TI - Alexithymia and obesity. Study of the impaired symbolic function by the Rorschach test. AB - Many authors consider alexithymia a predisposing factor to psychosomatic and somatopsychic pathologies. In this study we investigated the presence of alexithymic characteristics in a group of 106 massive obese patients who requested a surgical intervention. 6 Rorschach alexithymia variables in the protocols of patients and a non-patient reference group (n = 600) were studied. Findings supported the presence of a striking alexithymic element among severely obese patients in comparison with their lean counterparts. PMID- 1518923 TI - Relationship between conjugate lateral eye movements and alexithymia. AB - The relationship between conjugate lateral eye movements (CLEMs) and alexithymia was investigated in a group of 60 (23 male and 37 female) right-handed university students. Subjects completed the Toronto Alexithymia Scale (TAS), the Schalling Sifneos Personality Scale, and the Basic Personality Inventory, which measures 12 basic dimensions of personality and psychopathology, CLEMs were recorded while subjects were asked 20 general knowledge questions that have no tendency to elicit eye movements predominantly in one direction. A series of gender by CLEM preference (left vs. right mover) ANOVAs were conducted with the various measures. There was a significant relationship between right CLEM preference and higher scores on the TAS, but no relationships between CLEMs and any of the other measures. These results suggest that alexithymia is associated with left cerebral lateralization, and support the hypothesis that alexithymic characteristics reflect a variation in brain organization. PMID- 1518924 TI - Problems and prospects in the theory of gel electrophoresis of DNA. PMID- 1518925 TI - Mutational studies of protein structures and their stabilities. PMID- 1518926 TI - Selected topics in pediatric ultrasonography--1992. AB - In children, ultrasonography has been valuable in demonstrating a wide range of congenital lesions that were previously seen indirectly or only after more invasive procedures. It has replaced many studies that necessitated oral or vascular contrast and ionizing radiation. Real-time ultrasonography has found a role in the evaluation of the diaphragm, gastroesophageal reflux, bowel peristalsis, and hip stability. PMID- 1518927 TI - Recent advances in sonography of the testis and scrotum. AB - Ultrasonography remains an accurate, rapid, and safe tool in the imaging of disorders of the testes and scrotum. The strengths of gray scale sonography lie in its ability to distinguish intratesticular from extratesticular processes. Improvements in resolution permit greater confidence in the characterization of lesions as representing simple fluid, complex fluid, or solid lesions. The addition of flow information by color Doppler ultrasonography and duplex Doppler ultrasonography represents the most exciting recent advancement, permitting even more diagnostic information in the evaluation of these patients. PMID- 1518928 TI - Ultrasonographic evaluation of renal transplantation. AB - Ultrasonography of the renal transplant is still a key screening examination for transplant dysfunction. The addition of Doppler technology has permitted screening for hemodynamic alterations. Ambitious researchers predicted that these hemodynamic profiles would permit the differentiation of rejection from other complicating factors; however, recent research and clinical experience has shown this to be ineffective. Imaging identification of a dilated collecting system identifies the patient population that should undergo a Whitaker procedure. Identification of large or increasing fluid collections helps focus attention to possible hemorrhage or urine leak. Similarly, the ultrasonographic identification of a lymphocele as the cause of leg edema or hydronephrosis rapidly focuses surgical treatment. Doppler evaluation of hemodynamics must be performed on all renal transplant recipients. Although the role of the resistive index in predicting rejection has been minimized lately, numerous vascular complications, if untreated, would result in loss of the kidney. Doppler sonography identifies those patients who would benefit most from renal arteriography. The evaluation of renal morphology on the basis of ultrasonography alone has little role in predicting the cause of transplant dysfunction. We continue to evaluate renal size and to correlate it with the clinical presentation as well as resistive index to defer patients from biopsy if a more obvious cause of dysfunction is identified. PMID- 1518929 TI - Endoscopic ultrasonography of the upper gastrointestinal tract. AB - Endoscopic ultrasonography combines the advantages of conventional endoscopy with the capabilities of ultrasonography. This permits the examiner to see through the wall of the gastrointestinal tract. The close proximity permits the use of relatively high frequencies, with the resulting increase in tissue contrast and resolution. There are limitations to its use, however, with the main one being a field of view limited to a 7-cm radius. Discussed in this article is its use for the gastrointestinal wall, the esophagus, the stomach, the duodenum, and the pancreas. PMID- 1518930 TI - Intraoperative ultrasonography. AB - Four major benefits of intraoperative ultrasonography (IOU) were determined after its use in more than 2400 operations. They are the acquisition of new information not otherwise available, complement of or replacement for operative radiography, guidance of surgical procedure, and confirmation of completion of operation. IOU also has the advantages of safety, speed, higher accuracy, acquisition of more information, and wider application over operative radiography. Intraoperative color Doppler imaging, which has been introduced recently, seems to provide additional beneficial information during cardiovascular and general surgery. We believe that IOU should have a wider application and that surgeons and radiologists should develop cooperative working relations similar to those that exist for operative radiography. PMID- 1518931 TI - Ophthalmic ultrasonography. AB - Definition and differentiation of ocular structures and abnormalities necessitates the use of high-frequency, high-resolution, and high-definition ultrasound. Frequencies of 10 to 100 MHz are being employed. Color Doppler imaging, tissue characterization, parameter image staining, and three-dimensional volume rendering are new and useful adjuncts to ocular diagnosis. PMID- 1518932 TI - Ultrasonography of small parts. PMID- 1518933 TI - Arterial vascular ultrasonography. AB - A new generation of high frequency, high resolution ultrasound scanners has provided unprecedented information about the state of the arterial wall in a variety of superficial vessels and can document the disturbed flow within them. The information now available is of great clinical value to many clinicians, including vascular surgeons and subspecialty internists who care for individuals at risk for accelerated atherosclerosis and other vascular diseases. PMID- 1518934 TI - Venous ultrasonography. AB - Compression ultrasonography supplemented by pulsed and color Doppler imaging is the diagnostic modality of choice for evaluating lower extremity deep vein thrombosis in symptomatic and asymptomatic high-risk patients. Furthermore, this technique frequently can characterize the clot as occlusive or nonocclusive or acute or chronic and can define the extent of disease. In patients without thrombosis, this modality can suggest an alternative diagnosis in 12% of patients. PMID- 1518935 TI - Current status of intravascular ultrasonography. AB - Intravascular ultrasonography provides unique diagnostic information about vessel wall structure and underlying disease. It has been shown to be superior in both the detection of atherosclerotic plaque and in the quantification of extended disease. Future applications will include three-dimensional ultrasound and integration into interventional devices. It has been of particular clinical value in the performance of percutaneous atherectomy and intravascular stent deployment. PMID- 1518936 TI - Musculoskeletal ultrasonography. AB - The scope of musculoskeletal ultrasonography has broadened considerably since its inception. Ultrasonography has established itself as a reliable cost-effective modality for the diagnosis and follow-up of a wide variety of lesions. Its real time dynamic capability adds a perspective that other modalities lack. Growth within this field will continue, driven by improved technology, cost consciousness, and the creativity of those who employ this powerful diagnostic tool. PMID- 1518937 TI - Ultrasonography of the shoulder. AB - Shoulder sonography has been shown to be an effective noninvasive means of detecting rotator cuff tears and biceps tendon abnormalities. The examination requires careful attention to technique and a thorough knowledge of normal gross and sonographic anatomy. Rotator cuff tears generally cause a diffuse or focal decrease in the space between the humeral head and the deltoid muscle. Therefore, tears are easiest to detect by noting abnormally close apposition of the deltoid and humeral head. PMID- 1518938 TI - Ultrasonography of the neck. AB - The anatomic and pathologic involvement of the structures in the neck can be accurately studied with small parts ultrasonography. The thyroid and parathyroid glands and nodal chains are treated in this article; masses of the neck spaces are not considered because of their relative rarity. PMID- 1518939 TI - Transvaginal ultrasonography. AB - Transvaginal ultrasonography has provided new anatomic and pathophysiologic information about the female pelvis. Because of probe proximity to the organ of interest and higher insonating frequency, resolution is dramatically improved. Problems previously encountered during transabdominal scanning, such as obesity, bowel gas, and a retroverted uterus, no longer preclude accurate diagnosis. Patient acceptance is nearly universal. Physiologic information concerning the endometrium and ovarian follicles has improved infertility diagnosis and treatment. Hormonal and vascular Doppler changes can be correlated with cyclic endometrial patterns and follicle size. Oocyte retrieval, management of pre existing inflammatory disease, and treatment of complications of pregnancy are easier and safer with a transvaginal approach. Uterine malformations, leiomyomas, and cancers are more easily detected in premenopausal and postmenopausal women. The documentation of early intrauterine or ectopic pregnancy has decreased maternal morbidity and mortality. Tube-sparing procedures with preservation of reproductive potential are now more commonly employed due to earlier recognition of unruptured tubal pregnancy. Interventional TVS has led to improved recognition and treatment of pelvic cysts and abscesses and multiple pregnancy. Chorionic villous sampling can be performed more easily without the need for anesthesia, with adequate tissue obtained. PMID- 1518940 TI - Smaller parts scanning of the fetus. AB - Current instrumentation provides capabilities for minute fetal anatomic exploration and for integrative physiologic inference. This extends the complexity of the study and the diagnostic obligation of the examiner. The direction of study and clarification of findings devolve increasingly upon pathology and pathophysiology rather on than prior imaging experience. We believe that smaller parts scanning has a role in every fetal examination. An increasing number of reports in the literature attest to the improvement in anatomic imaging for first trimester detection of anomalies. Focused, microregion anatomic perusal is applicable throughout pregnancy, provides information for physiologic inference, and can be used for prediction of pathology, detection of abnormalities, and, in most examinations, in a wellness role of confirming normality. A conceptual paradox is associated with smaller parts scanning. As the examiner concentrate on progressively more minute regions and structures, it becomes increasingly important to analyze findings in a holistic, or perhaps holographic, context. This is evident in fetal studies in which any local facet of development affects the entire process of gestation. The specific signs we use for sampling the developmental process vary in utility and reliability depending on technical capabilities, operator expertise, and regional population effects. Fetal studies are inseparable from parental emotional, physical, and genetic factors, which must be recognized and addressed as the study proceeds. PMID- 1518941 TI - Breast ultrasonography. AB - Ultrasound of the breast has a role both as the primary and as an ancillary modality in the work-up of breast abnormalities. Its main role is to differentiate cystic from solid abnormalities and to thereby guide further work up and intervention. Only the diagnosis of a simple cyst will obviate the need for further evaluation or therapy. Doppler ultrasonography of breast lesions may give further information in the future, although this is currently not employed in clinical practice. Various types of ultrasound examinations may yield useful information in the patient with breast cancer or in women with breast prostheses. PMID- 1518942 TI - Transcatheter treatment of pulmonary outflow tract obstruction: a review. AB - The role of transcatheter methods in the management of pulmonary outflow tract obstruction are discussed in this review. Balloon pulmonary valvuloplasty for relief of isolated pulmonary valve stenosis has been successfully used by many investigators and is the procedure of choice for the management of these lesions. Supravalvar pulmonic stenosis, if discrete, can be relieved by balloon dilatation. Cyanotic children with interatrial right-to-left shunts secondary to severe valvar pulmonary stenosis respond in a manner similar to that observed with isolated pulmonary valve stenosis. In these patients, balloon valvuloplasty is the treatment of choice and may be corrective in most patients. In patients with interventricular right-to-left shunting secondary to pulmonary outflow tract obstruction and in patients with narrowed BT shunts, balloon dilatation may be an effective palliative procedure in a substantial proportion of patients obviating the need for an initial or second palliative shunt. Balloon dilatation is recommended if the patient's size or cardiac anatomy make them unsuitable for safe total surgical correction. In patients with pulmonary atresia, either initial opening of the atretic pulmonary valve by laser or by surgery with subsequent balloon dilatation are potentially beneficial in reducing the total number of surgical procedures that these children are likely to require. However, further clinical trials are needed before their general use. PMID- 1518943 TI - Weight training in coronary artery disease and hypertension. PMID- 1518944 TI - Prognostic implications of transient asymptomatic myocardial ischemia as detected by ambulatory electrocardiographic monitoring. PMID- 1518945 TI - [The postgraduate nursing network in the southern region--a shared challenge]. PMID- 1518946 TI - [The reference and counter-reference system in a community health service]. AB - This study has been carried out at the Community Health Service of the Conceicao Hospital/Porto Alegre/RS, with the aim of describing its reference and contra reference system. After two weeks observing this system, patients were interviewed at home. The results showed the demand of the service relating to the various levels of assistance. Some problems that prevent the reference system from its best functioning in this service were also pointed out. PMID- 1518947 TI - [Developing critical thinking on the questions of nursing teaching and practice]. AB - The aim of this article is to offer an overview about the applicability of critical thinking to nursing education and nursing practice. Following, Brookfiels's (1987) model is applied to nursing situations. PMID- 1518948 TI - [Is nursing a science or a profession?]. AB - Traditionally, human knowledge has been considered in the context of disciplines which can be divided in two groups: Academics and professionals. The aim of academic disciplines is the knowledge and their theories are descriptive in nature. For this reason they are named science. In contrast, professional disciplines are move comprehensive, directed toward practical aims and there is a need to and to work. Nursing as a professional discipline has been influenced by four school of thought named; service, administration, academic and practice. Currently the nursing practice is developed based on three different theoretic and philosophic branches. PMID- 1518949 TI - [The thinking about women, health and work in the hospital]. AB - This article deals with the relation women, health and work at hospital. Working relationships are thought in a gender perspective represented in a sexual division of work. Through a discussion about this subject, we intend to rise questions and reflect upon the reality of health care female workers. PMID- 1518950 TI - [Reflections on the introduction of informatics into the nursing profession]. AB - The paper is an analysis about the impact of introducing informative technology and its consequences in the society, in general professions and mainly, in nursing practice. The authors emphasize the need of major discussions about the insertion of this new technology in nursing profession. PMID- 1518951 TI - [Invasive procedures and complications in patients with craniocerebral trauma hospitalized in an intensive therapy unit]. AB - The present study realized with 50 patients from an Intensive Care Unit, due to head injury and considering that the majority of them presented a score equal or below six (6) in the Glasgow Coma Scale, has shown that the utilization of invasive procedures is high. Regarding complications, there was predominance of fever, upper airway secretions, hematomas at the arterial puncture localization and diarrhea. Proportionally, the patients under a clinical treatment presented a lower number of invasive procedures and problems and the reverse occurred with those under surgery. The analysis of the association of the invasive procedures and problems compared to the level of consciousness has been affected. PMID- 1518952 TI - [An analysis of the socioeconomic and reproductive conditions of women from a peripheral community of Porto Alegre, Rio Grande do Sul]. AB - This work is based on the analysis of a research where the socioeconomic conditions of women, with ages ranging from 15 to 44 years old, living in a community situated in the outskirts of Porto Alegre, were investigated. A relation was established between those conditions and the reproductive behavior of the subjects. PMID- 1518953 TI - Immunoblotting as a valuable tool to differentiate human visceral leishmaniasis from lymphoproliferative disorders and other clinically similar diseases. AB - Diseases presenting with splenomegaly, fever and pancytopenia require intensive differential diagnostic considerations. These diseases include lymphoproliferative and autoimmune diseases, but also chronic infections like mansonian schistosomiasis or visceral leishmaniasis (kala-azar). Diagnosis for the latter is usually performed by testing for the presence of antileishmanial antibodies using the immunofluorescence test (IFT) or the enzyme-linked immunosorbent assay (ELISA) technique. Here, we report on patients who displayed positive antileishmanial antibody titres in the IFT and/or ELISA, but did not develop kala-azar and were eventually diagnosed as having one of the non-kala azar diseases listed above. These false-positive sera proved to be seronegative when tested on a Leishmania immunoblot. Our studies lead us to recommend the immunoblot technique as a confirmatory test in cases with doubtful IFT or ELISA antibody titres. PMID- 1518954 TI - Milky spots in the mouse omentum may play an important role in the origin of peritoneal macrophages. AB - In the milky spots, precursors of cells belonging to the mononuclear phagocyte system (MPS), such as monoblasts, can be found on the basis of ultrastructural endogenous peroxidase cytochemistry. Therefore, in the present study, we investigated the milky spots using a panel of monoclonal antibodies, especially antibodies (ER-MP) that recognize macrophage precursor antigens. Early macrophage precursor antigens ER-MP12 and ER-MP58 were detected only on cells localized inside the milky spots. On the other hand, an antigen which disappears late in the course of macrophage differentiation, ER-MP20, was detected in high amounts on cells both inside and around the milky spots. This clearly indicates that macrophage precursors are centrally localized inside the milky spots, while more differentiated cells are found in peripheral areas. Moreover, long-term culture of milky spot tissue resulted in the forming of a monolayer of stromal cells which supported macrophage proliferation in vitro. In conclusion, both in situ and in vitro studies demonstrated that mouse milky spots have a microenvironment in which precursor cells of the MPS can home and proliferate, illustrating that milky spots play a role as a source of local macrophage generation, e.g. that of the free peritoneal macrophages. PMID- 1518955 TI - Changing the name of the major histocompatibility complex. PMID- 1518956 TI - Correlation between a hepatic copper accumulation and an altered expression of glutathione S-transferase Ya/Yc subunits in LEC mutant rat. AB - Long-Evans Cinnamon (LEC) rat, an animal model of Wilson's disease, that develops a necrotizing hepatic injury with an abnormally high hepatic copper accumulation exhibits an altered expression of glutathione S-transferase (GST) subunits, that is, a low percentage of the Ya and a high percentage of the Yc subunit expression in males. The altered expression of GST subunits and the abnormal copper accumulation in liver were found to be completely correlated in male LEC mutant rat liver, suggesting that the copper toxicity caused by the anomaly of copper metabolism in LEC rat liver leads to the altered expression of GST subunits. PMID- 1518957 TI - Effect of p-xylene metabolites, p-methylbenzyl alcohol and 2,5-dimethylphenol, on rat hepatic and pulmonary microsomal metabolism. AB - Pulmonary metabolites of p-xylene, p-methylbenzyl alcohol (PMBA) and 2,5 dimethylphenol (DMP), were employed to investigate the divergent effects of p xylene on pulmonary and hepatic metabolism. Rats were given PMBA, DMP, or 10% cremophore (control) ip daily for 3 days, and effects on hepatic and pulmonary microsomal metabolism were determined 12 hours later. Both PMBA and DMP mimic the decrease in pulmonary benzyloxyresorufin-O-debenzylase activity previously reported for p-xylene, but neither could account for the potent induction of cytochrome P450 in the liver. Only PMBA had a consistent effect on P450IIB apoprotein levels, decreasing them in both the liver and lung. These data suggest that PMBA may have a significant role in the inhibition of pulmonary P450 caused by p-xylene. PMID- 1518958 TI - The effects of isoproterenol on the isolated perfused rat heart. AB - In isolated hearts infused with up to 100 ug/ml isoproterenol (ISO), there was only a transient effect on the frequency of contraction, and no effect on buffer flow through the heart. Infusion of hearts with 40-60 or 70-100 ug/ml ISO produced an increase in the release of lactate dehydrogenase, but not creatine kinase. Microscopic examination of hearts revealed myocyte separation and cytoplasmic vacuolation, of similar severity, in both control and ISO infused hearts; there was no necrosis. The data from this experiment are consistent with the view that ISO has little or no direct toxic effect on the heart. Since ISO is cardiotoxic In vivo, it is reasonable to suppose that this toxicity is linked primarily to the pharmacological effects of the drug. However, our study does not exclude the possibility that under the stressed conditions prevailing in vivo following a challenge with ISO, the susceptibility of myocytes to a direct toxic effect of ISO may increase. PMID- 1518959 TI - Factors affecting acetohexamide reductase activities in microsomes and cytosol from the kidney of male rats: age and castration. AB - Acetohexamide reductase activity in microsomes from the kidney of male rats increased markedly at puberty to approach the maximum level at 8 weeks of age; it was not detected until 4 weeks of age. Furthermore, castration suppressed effectively the activity in kidney microsomes at 8 weeks of age. These findings clearly indicate that the activity in kidney microsomes can be regulated by androgens. On the other hand, in cytosol from the kidney of male rats, a higher acetohexamide reductase activity was observed at all weeks of age tested. Castration had no significant effect on the activity in kidney cytosol. PMID- 1518960 TI - Identification of a constitutive form of cytochrome P-450 with high activity towards macrolide antibiotics in Syrian golden hamster liver. AB - The presence of cytochromes P450 belonging to the P450IIIA family was investigated in the liver of untreated Syrian golden hamsters and compared to those of untreated, phenobarbital- and dexamethasone-treated rats. The microsomal preparations from untreated Syrian golden hamster livers exhibited higher activities of N-demethylation towards the macrolide antibiotics, erythromycin and troleandomycin, than those from untreated and phenobarbital-treated rats. Western blots analysis revealed larger amounts of proteins immunorelated to the rat cytochrome P450IIIA1 isozyme in Syrian golden hamster liver than in untreated and phenobarbital-treated rats. The N-demethylation of erythromycin and troleandomycin were strongly inhibited after preincubation of the microsomes from Syrian golden hamsters with anti-P450IIIA1. We conclude that a cytochrome P450 belonging to the P450IIIA family is expressed constitutively in the liver from Syrian golden hamsters, whereas it is not in rat liver. PMID- 1518961 TI - Clinical significance of benzoate-metabolizing capacity in patients with chronic liver disease: pharmacokinetic analysis. AB - Benzoate-metabolizing capacity was studied in control subjects and in liver disease patients after intra-venous loading of 15 mg benzoate per kg of body weight. In the 7 control subjects, the mean level (+/- SEM) of Cmax for serum benzoate was 104.1 +/- 6.8 micrograms/ml, AUC was 2.57 +/- 0.32 mg.min/ml, MRT was 21.5 +/- 1.5 min and T1/2 was 15.5 +/- 1.3 min. For serum hippurate, on the other hand, Tmax was 27.9 +/- 6.0 min, Cmax was 33.4 +/- 2.1 micrograms/ml, AUC was 1.96 +/- 0.13 mg.min/ml, MRT was 39.6 +/- 2.9 min and T1/2 was 30.7 +/- 2.4 min. In 12 patients with chronic hepatitis, Cmax, AUC, MRT and T1/2 for benzoate and Tmax, MRT and T1/2 for hippurate remained at control levels, but Cmax and AUC for hippurate were slightly decreased compared to controls. However, in 18 patients with liver cirrhosis, Cmax and AUC for benzoate were in the control range but MRT and T1/2 were significantly delayed (p less than 0.01 for both). Moreover, the MRT value was increased in proportion to the severity of liver disease (p less than 0.01). AUC for hippurate was not changed to any extent, and Tmax, MRT and T1/2 were slightly delayed, while Cmax was significantly reduced. AUC, MRT and T1/2 for benzoate and Tmax, MRT and T1/2 for hippurate showed significant correlation with serum albumin levels, prothrombin time and indocyanine green clearance rate. These results suggest that benzoate metabolizing capacity, especially as indicated by the MRT value for serum benzoate, appears to be a better index than the indocyanine green clearance rate for determining hepatic functional reserve in chronic liver disease. PMID- 1518962 TI - A novel two-site enzyme immunoassay for the sensitive detection of beta-endorphin in specific human brain stem regions. AB - On the line of experiences previously made in the development of a two-site immunoradiometric assay (TS-IRMA), we generated, in the present study, a novel, sequential, noncompetitive two-site immunoenzymometric assay (TS-IEMA) for the determination of the non-acetylated form of human beta-endorphin (beta h-EP). At variance with other assays reported in the literature, but in analogy to the TS IRMA, the TS-IEMA does not require previous separation of beta h-EP. The TS-IEMA detects beta h-EP in central nervous tissues at a very low detection limit, and to a high degree of reproducibility, precision, sensitivity, and accuracy. The newly developed assay was then used to determine beta h-EP levels in the tissues of distinct brainstem regions. Tissues were collected, by the Palkovits's punching technique, from a series of victims of "Sudden Infant Death Syndrome" and of miscellaneous infections. The TS-IEMA, combined with the punching technique, has revealed, in the measure of its application in the present study, an unprecedented high degree of resolution of the neurochemical architecture of beta h-EP in the human infantile brainstem. PMID- 1518963 TI - Newly evidenced pyrimidinoceptors and the P2x purinoceptors are present on the vascular smooth muscle and respectively mediate the UTP- and ATP-induced contractions of the dog maxillary internal vein. AB - P2 purinergic receptors and pyrimidinoceptors were studied by comparing the contractile responses to UTP with those to ATP, in the dog internal maxillary vein (IMV) after endothelium removal. The contraction curves were very different: rapid subsidence with ATP and sustained contraction with UTP. alpha beta methylene ATP induced desensitization to ATP, whereas it did not antagonize the UTP-induced contractions. Reactive blue 2 (RB2) was incapable of antagonizing contractions to ATP and UTP in this vessel. We showed that Nicardipine, a calcium antagonist, was more potent on the UTP-induced than on the ATP-induced contractions. The fact that RB2 did not potentialize the UTP-induced contractions, unlike what has been observed in the dog saphenous vein, suggests that a new category of pyrimidinoceptors have been evidenced on the IMV. Our results also indicate that ATP induces contraction via P2x rather than P2y purinoceptors. The receptors described here are localized on the vascular smooth muscle. PMID- 1518964 TI - Collagenolytic cathepsin B and L activity in experimental fibrotic liver and human liver. AB - To clarify the role of individual collagenolytic cathepsin in hepatic collagen degradation, cathepsin B and L activities were determined in normal and CCl4 induced fibrotic liver, together with non-collagenolytic cathepsin H. Cathepsin B and L activities increased 1.9- and 2.0- fold, respectively, in the fibrotic liver as compared with the normal liver, and were significantly correlated with hepatic hydroxyproline levels. By contrast, cathepsin H activity was not altered in fibrotic rats. Similar results were also obtained from autopsied human livers. These results suggest that cathepsin B and L are similarly induced by hepatic collagen levels and are implicated in degrading collagens, especially soluble collagen. PMID- 1518965 TI - Cross-reactive potential of monoclonal antibodies raised against proteolysed tobacco etch virus. AB - Monoclonal antibodies (mAb) capable of reacting with different potyviruses were obtained by immunizing mice with proteolysed tobacco etch virus. The mAb were not equally effective in all ELISA formats and some were specific for different conformational states of the viral coat protein. The mAb also detected antigenic differences between purified virus particles and viral antigen in infected plant sap. In an ELISA format using antigen-coated plates, 5 different potyviruses (out of 7 viruses tested) could be detected in plant sap by one mAb. Different combinations of mAb and polyclonal antiserum could also be used for detecting several potyviruses by ELISA. PMID- 1518966 TI - Association between HIV1 infection and sexually transmitted disease among men in Central Africa. AB - In Africa, heterosexual contact is the major route of transmission of the human immunodeficiency virus (HIV). Previous studies have strongly suggested that other sexually transmitted diseases (STD) may facilitate HIV transmission. However, the association of HIV infection with other STD may simply be a marker of sexual promiscuity. Thus, we compared the association of different STD, HIV status, and sexual behaviour of 160 STD patients and 95 STD-free control individuals. Results showed that STD patients differed from controls in most of the sociological and behavioural parameters, as well as in HIV serological status. Within the STD group, people with genital ulcer disease (GUD) (n = 62) were more likely to be HIV-seropositive (21%) than people with urethritis (n = 98, 11.2%). Meanwhile, there was almost no difference in the sociological and behavioural parameters between the GUD and the urethritis group. Thus, our results reinforce the specific role of mucosal breakage (i.e. genital ulcers) in the transmission of HIV. PMID- 1518967 TI - Electron microscopic identification of Zinga virus as a strain of Rift Valley fever virus. AB - Electron microscopic examination of a negatively stained suspension of Zinga virus showed particles 90-100 nm in diameter, enveloped with spikes 12-20 nm in length and 5 nm in diameter. Further identification of the virus by immune electron microscopy showed the reactivity of human Rift Valley fever virus positive serum with Zinga virus. Results of this study are in agreement with earlier reports that Zinga virus is a strain of Rift Valley fever virus. PMID- 1518968 TI - Comments arising from the "discussion" of the 4th Forum in Virology, "Clinical significance of drug-resistant viruses" (Res. Virol., 1992, 143, 2) PMID- 1518969 TI - [Definition of the non-Q wave myocardial infarction]. PMID- 1518970 TI - [Electrocardiographic and clinical characteristics of non-Q myocardial infarction]. PMID- 1518971 TI - [Coronary angiographic findings in non-Q wave myocardial infarction]. PMID- 1518972 TI - [Prognosis and treatment of non-Q-wave myocardial infarction]. PMID- 1518973 TI - [Intra-bullous ventilation of giant bulla: does slow ventilation space on multi breath nitrogen washout test mean that giant bulla is present?]. AB - Intra-bullous ventilation and uneven ventilation in patients with giant bulla were studied by the multi-breath nitrogen washout and 133Xe washout tests. Fourteen patients underwent the nitrogen washout test before and after bullectomy; 2 of them also underwent the 133Xe washout test before surgery. After bullectomy, pulmonary nitrogen clearance delay and alveolar dilution rate (ADR) of slow ventilation space improved significantly (p less than 0.01) from 202.5% to 51.5%, and from 0.98 to 0.95, respectively. The dilution rate of 133Xe in the bullous region, based on the 133Xe clearance curve, showed the same values as the nitrogen washout test. Therefore, we considered that bullous ventilation could be estimated by the ADR of the nitrogen washout test and that uneven ventilation resulted from the ADR difference between the giant bulla and the nonbullous lung. When the nonbullous lung region was emphysematous, however, it was impossible to estimate the intra-bullous ventilation from the nitrogen washout test. PMID- 1518974 TI - [Validation of Doppler arterial flow in humans]. AB - A method of measuring volumetric flow in human arteries with pulsed Doppler technique was developed. Doppler flowmetry was assessed in 11 adult patients whose admission-diagnoses included aneurysm of the aorta or dissections. During surgery, regional blood flows of the left common carotid artery, terminal aorta, common iliac artery, external iliac artery or common femoral artery were measured by Doppler method and electromagnetic flowmeter. Eighty four arterial flow determinations were obtained from the 11 patients studied. On comparison of simultaneous electromagnetic and Doppler measurements of blood flow, an excellent correlation (r = 0.93) was found between the two methods. The slope of the regression line was 0.587. Regional blood flow was measured with Doppler flowmetry in another 9 patients. The values of the left common carotid, celiac, superior mesenteric and terminal aortic flows were 251 +/- 62, 608 +/- 399, 687 +/- 381, 783 +/- 324 ml.min-1, respectively. This method provides an easy, reliable way of measuring regional blood flow. PMID- 1518975 TI - [A case report of primary pulmonary hypertension: congestive heart failure induced by pregnancy and delivery]. AB - A thirty-year-old woman had complaints of general fatigue and gain in body weight, which had developed since the third trimester of pregnancy. On admission, she had lip cyanosis, general edema, and tachycardia. A chest rentogenogram showed cardiomegaly and dilatation of the pulmonary arteries. On cardiac catheterization, pulmonary artery pressure and pulmonary vascular resistance were elevated moderately. A pulmonary perfusion scintigram revealed a defect in the left lower lung field with no evidence of thrombus in a pulmonary artery angiogram. In this case, an underlying disease which caused pulmonary hypertension might have been the underfined cause. For this reason, primary pulmonary hypertension was the diagnosis. In the present case there is a danger that congestive heart failure may be induced by pregnancy and delivery and, furthermore, there is a possibility that during the clinical course of the illness pulmonary infarction might occur. PMID- 1518976 TI - [Repeated blackout in a patient with accelerated idioventricular rhythm]. AB - There has been no report that Accelerated Idioventricular rhythm (AIVR) causes a syncope attack. The patient described in this report is very rare because AIVR chronic without any heart diseases has been observed for 13 years, and because it is considered that AIVR is closely associated with his repeated blackouts. A 62 year-old male was admitted to our hospital because of repeated syncopal attacks. He reported that he occasionally felt lightheaded after strenuous lifting and pushing or pulling against resistance. We found that AIVR could produce a remarkable arterial pressure drop partly because of ventricular asynergy and loss of timed atrial contribution. Furthermore, we observed syncopal attacks during Valsalva maneuver and found abnormalities of baroreceptor reflex (Lack of reflex tachycardia and weakened evershoot phenomenon). It is concluded that AIVR is not a benign arrhythmia in this patient because it has been a possible cause of syncope attack due to systemic arterial pressure drop and baroreceptor abnormalities. PMID- 1518977 TI - [A case of acute myocardial infarction following intracoronary thrombi caused by coronary artery spasm]. AB - A 65-year-old man underwent coronary angiography (CAG) after 10 hours from the onset of myocardial infarction. We observed large Thrombi at the filling defect in the proximal site and mid-portion of the right coronary artery. CAG showed that they had disappeared completely without residual stenosis on the 4th day. In addition to this segmental spasms developed spontaneously at the proximal site of a thrombus accompanied by ST elevation, but these spasms recovered after intracoronary infusion of isosorbide dinitrate on the 26th day CAG. Thus, our case indicates that acute myocardial infarction may be caused by secondary coronary artery thrombosis and accompanying coronary artery spasm. PMID- 1518978 TI - [Report of a case with aortic regurgitation in progressive systemic sclerosis]. AB - Aortic valve lesions in progressive systemic sclerosis (PSS) are very uncommon. To our knowledge, aortic regurgitation (AR) associated with PSS has not been reported previously. We would like to report the case of a 58-year-old woman who had PSS with AR due to Raynaud's symptom, fever, positive ANA, accelerated ESR, and diastolic blowing murmur along the left sternal border. After treatment with adreno-cortico steroid and an immunosuppressive agent, the patient improved serologically and symptomatically. However, she was later admitted to our hospital again due to heart failure with progressive AR. She died of refractory heart failure with severe AR and tricuspid regurgitation (TR). The former was caused by aortic cusp lesions and the latter by pulmonary hypertension. An autopsy confirmed the diagnosis of PSS, which was found to have involved the heart, lungs and pancreas. Vasculitis with infiltration and fibrotic changes were noted in these organs. Moreover, there were fibrotic thickenings and shortenings in the aortic cusps with cell infiltration. There were no indications of rheumatic disease. These results suggest that the cause of our patient's aortic valve disease may have been PSS vasculitis. PMID- 1518979 TI - [A case of subarachnoid hemorrhage with sick sinus and advanced AV block]. AB - A 35-year-old man was hospitalized after a sudden onset of transient syncopal attack without accompanying complaints of headache or nausea. He was slightly disorientated but neurologically normal. He had a blood pressure of 150/90mmHg and a pulse rate of 40/min. An ECG showed marked sinus brady-cardia with ventricular escaped rhythm followed by advanced atrioventricular (AV) block. Some components of conducted ventricular beats showed aberration. There was no significant ST or T wave abnormality in normally captured QRS components except for prominent T in leads II, III and aVF. At first, we thought that he might require temporary pacing because of Adams-Stokes attack. However, after administration of atropine sulfate, the ECG returned to normal sinus rhythm with heart rate of 88/min. Then he began to complain of headache followed by a convulsive seizure. A CT scan and angiogram revealed a ruptured aneurysm at the top of the basilar artery, which was successfully clipped. A wide spectrum of ECG changes can be demonstrated in practically all patients with subarachnoid hemorrhage (SAH). Prolonged QT interval, ST-T changes, U wave, sinus tachycardia, or ventricular premature complex are the common abnormalities probably caused by increased circulating catecholamine. As bradyarrhythmia in patients with SAH is an uncommon finding, its mechanism has not yet been defined. Transient sinus bradycardia with advanced AV block in this patient might have been caused not by elevated intracranial pressure (Cushing phenomenon) but by drastic discharge of the parasympathetic nerve. This case serves to illustrate the vigilance required in determining whether abnormalities of cardiac rhythm are instrumental in causing neurological symptoms and signs or a disorder of cerebral function. PMID- 1518980 TI - [A case of angina pectoris with cardiac arrest at treadmill stress test]. AB - We reported a case of angina pectoris with cardiac arrest immediately after treadmill exercise test, and the effect of PTCA in the same case. A 69-year-old Japanese male had chest oppression on exertion. Initial treadmill test showed 2 mm ST-segment depression in leads V4-6. Two minutes after exercise, he had atrio ventricular (A-V) block and cardiac arrest with episodes of fainting. He was resuscitated by chest thump. Coronary angiography showed 90% stenosis in the right coronary artery (RCA). PTCA for RCA was able to dilate the stenotic lesion. The second treadmill test after PTCA did not induce bradycardia nor A-V block. It was suggested that the RCA lesion may play a critical role. PMID- 1518981 TI - [Two cases of vocal cord dysfunction and bronchial asthma indicated contrary course of bronchial responsiveness based on astography]. AB - We encountered two cases of patients who showed vocal cord dysfunction and bronchial asthma. By using an ++astograph , we found that bronchial responsiveness of these ailments differed. In the case of vocal cord dysfunction, bronchial responsiveness to methacholine indicated a false high level by adduction of the vocal cord. Therefore other evaluations including pulmonary function and bronchoscopy were required to distinguish it from bronchial asthma. On the other hand, in the case of bronchial asthma, bronchial responsiveness to methacholine was mild, but life threatening asthmatic attack occurred after inhalation of methacholine. Psychological factors were not neglected in considering both of these cases. Therefore we must consider these results and psychological factors when evaluating bronchial responsiveness. PMID- 1518982 TI - Structure and function of the external gill filaments of embryonic skates (Raja erinacea). AB - We have investigated structure and function of the external gill filaments, which occur transiently in the embryonic little skate, Raja erinacea. Approximately 25 30 days after spawning (body mass 0.03-0.05 g) external gill filaments appear as an outgrowth from the caudal side of the gill arches. These filaments are thread like, each containing one afferent and one efferent blood vessel, and by day 70 75 (body mass 0.4-0.5 g) they reach their maximum size at a length of about 1 cm and a blood vessel diameter of 70-80 microns. Subsequent resorption of the filaments is characterized by a decrease in both length and diameter of the blood vessel. By day 90-95 (body mass 0.9-1.0 g) the external gill filaments are completely resorbed and replaced by internal gills. Blood velocity, measured in these external filaments, increased with development from 0.1 mm.sec-1 to about 0.7 min.sec-1, and decreased again during resorption. Blood flow, calculated therefrom with blood vessel diameter, showed a similar maximum curve. A model analysis supports the hypothesis that in a full grown filament respiratory gas exchange is mainly perfusion-limited and can contribute significantly to the total oxygen uptake of the embryo. Analysis of the results indicates, however, that the gill filaments are not adequate as a gas exchange organ for later developmental stages. PMID- 1518983 TI - Capillary-to-fiber geometry and mitochondrial density in hummingbird flight muscle. AB - We investigated structural characteristics for high O2 flux in hummingbird flight muscle, i.e. the most O2 demanding skeletal muscle per unit tissue mass among vertebrates. Pectoralis and supracoracoideus muscles of 3-4 g hummingbirds (Selaphorus rufus) were perfusion fixed in situ, processed for electron microscopy and analyzed by morphometry. Small fiber size (group mean +/- SE, 201 +/- 14 microns 2 at 2.1 microns sarcomere length), large capillary length per fiber volume (8947 +/- 869 mm-2) and high mitochondrial volume density per volume of muscle fiber (34.5 +/- 0.9%) were characteristic features of the muscles. Considering capillary supply and mitochondrial volume on an individual fiber basis showed that the size of the capillary-to-fiber interface (i.e. capillary surface per fiber surface) was also high in the muscles. Comparison with mammalian hindlimb pointed to a major role of the size of the capillary-to-fiber interface in providing a great potential for O2 flux rate from capillary to muscle fiber mitochondria in hummingbird flight muscle. PMID- 1518984 TI - Influence of lung volume history and increased surface forces on collateral resistance. AB - In order to investigate the major route for collateral ventilation, the influences of lung volume history and increased surface forces on collateral resistance (Rcoll) were studied in excised canine lower lobes. Measurements were made during inflation and deflation in two states, i.e. before (control) and after stiffening by large tidal ventilation raising peak recoil pressure (Ptp) by 8-10 cmH2O. Air flowed into a wedged segment via a double lumen catheter (Vcoll) keeping segmental pressure (PS) constant at 2 cmH2O as monitored through the other lumen, giving Rcoll = Ps/Vcoll. Rcoll vs lung volume (VL) showed little hysteresis, in sharp contrast to Rcoll vs Ptp (Rcoll higher during inflation). Thus, in each state, Gcoll (= 1/Rcoll) depended primarily on VL, but the stiffed state appeared to have permanently enlarged channels or recruited new ones. The relations between Gcoll and VL or Ptp somewhat resemble reported bronchial diameter behaviour. The ventilation process itself, rather than higher surface forces per se, appeared to distend collateral channels in the stiff lung. The results are consistent with the major component of Gcoll being located at the bronchiole level. PMID- 1518985 TI - Mechanical independence of wingbeat and breathing in starlings. AB - The pectoral muscles in birds comprise up to a third of the body weight and provide the principal drive to the wing. Their attachment to the sternum suggests that they could compress the thorax and assist ventilation during flight. Most, but not all, birds have an integer ratio relationship between wingbeat and breathing frequency, but no measurements of the respiratory flow associated with the act of wingbeat are available. We recorded respiratory flow and wing timing in three starlings that flew at 22 knots (11 m.s-1) for up to 5 min in a wind tunnel. Triggering on wingbeat, we ensemble averaged flow records for many wingbeats in each flight. Because wingbeats occurred throughout the respiratory cycle, breathing flow tended to average to zero, and a small flow event related to wingbeat emerged. The volume change associated with wingbeat ranged from 3 to 11% of tidal volume, and this is probably an overestimate. We conclude that wingbeat and breathing in starlings are essentially mechanically independent, despite the direct attachment of the locomotor muscles to the thorax. PMID- 1518986 TI - Breath-to-breath variability in hypoglossal motor unit firing. AB - Instability in the magnitude and timing of motor output to pharyngeal dilator muscles occurs during breathing. This contributes to alterations in upper airway resistance, and is one of several factors that play a role in the pathophysiology of obstructive apneas. To define the motor unit mechanisms accounting for such variability, geniohyoid motor unit activity was recorded simultaneously with diaphragm EMG in anesthetized cats spontaneously breathing 7% CO2 in O2. Variability was quantified with the coefficient of variation [CV = (SD/mean) x 100%]. In this preparation, we confirmed greater breath-to-breath variability of geniohyoid compared to diaphragm peak moving average EMGs. During recordings of geniohyoid motor unit activity, average CV of other respiratory parameters were as follows: peak diaphragm EMG 5.8%, inspiratory time 3.5%, expiratory time 3.8%. The average CV for geniohyoid motor unit activity patterns were substantially higher: spikes per breath 15.6%, mean firing frequency 13.3%, peak firing frequency 19.0%, minimal firing frequency 26.3%, onset time 40.9%, offset time 10.0% and duration of firing 12.8%. Values differed considerably among motor units, even when activity was recorded simultaneously. These findings suggest that variability is present in both intensity and timing of geniohyoid motor unit firing during breathing, and that different geniohyoid motor units appear to have varying degrees of stability during breathing. PMID- 1518987 TI - Ventilatory response to sustained eucapnic hypoxia in the adult conscious dog. AB - The ventilatory response to 20 min sustained isocapnic hypoxia (SaO2, 80 +/- 2%) was examined in 5 trained unanesthetized adult dogs breathing through an endotracheal tube. End tidal PCO2 was maintained at the resting levels. The dogs' conscious status was monitored by recording EEG and EOG on a chart recorder. The room temperature was kept between 19 and 21 degrees C. All tests were repeated in each dog on 2 occasions: (1) unloaded tracheal breathing or (2) resistive loaded breathing. During unloaded tracheal breathing, the average ventilation in response to sustained hypoxia rose from a control of 5.1 +/- 0.3 L/min (mean +/- within-dog SE) to 19.2 +/- 1.1 L/min at the initial stage of hypoxia. Ventilation remained at 20.7 +/- 1.3 L/min at 10 min, and then 19.7 +/- 1.4 L/min at the completion of the 20 min hypoxic exposure. There was no ventilatory adaptation observed (P greater than 0.05). After release from hypoxia, the ventilation fell abruptly to 7.6 +/- 0.8 L/min, which was higher than the resting baseline level (P less than 0.05), and then gradually returned to the resting baseline within 10 min. Experiments exposing the dogs to 40 min sustained hypoxia also failed to elicit significant adaptation. During resistive loading, the pattern of average ventilation in response to sustained hypoxia was similar to that observed in unloaded breathing tests. But the ventilatory recovery was longer than unloaded breathing, returning to the resting baseline within 20 min. Again, there was no ventilatory adaptation observed.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1518988 TI - Respiratory response to positive and negative inspiratory pressure in humans. AB - To investigate the effect of positive or negative inspiratory pressure on respiration, eight subjects breathed, either without or with added external dead space (VD, 600 ml), through either added inspiratory laminar flow resistances (RES; peak inspiratory airway pressure, Pinsp, down to -9 cmH2O) or with inspiratory pressure support (IPS; Pinsp up to +10 cmH2O). IPS, triggered by the subject's inspiratory effort, provided positive airway pressure throughout inspiration, but allowed for attainment of the subject's own respiratory pattern. The following main results were obtained with IPS or RES relative to the control (no IPS, no RES): (1) with VD, IPS led to small, but significant, increases in tidal volume (VT), respiratory frequency (fR) and ventilation (VE), with no changes in inspiratory time (TI) or duty cycle (TI/TT). Mean inspiratory flow (VT/TI) increased, and mouth occlusion pressure 0.1 sec after onset of inspiration (P0.1) decreased significantly with IPS. The changes during RES were essentially in the opposite direction; (2) without VD, similar, but smaller effects were observed, and only the changes in VT/TI and P0.1 during IPS were significant; (3) highly significant decreases were observed during IPS in end tidal PCO2 (PETCO2); on the average from 39.6 to 29.2 Torr without VD, and from 45.7 to 39.3 Torr with VD breathing. A small, but significant decrease in PETCO2 occurred also during RES with VD. We conclude that while resistive loading is nearly completely compensated with but small changes in PETCO2, inspiratory pressure support leads to marked hyperventilation, which is not effectively counteracted by central timing commands. PMID- 1518989 TI - Airway anesthesia during positive and negative inspiratory pressure breathing in man. AB - We have measured the effects of airway anesthesia (aerosolized 5% lidocaine) on the respiratory pattern during positive or negative inspiratory pressure in 8 resting subjects. The subjects breathed through a 600 ml dead space (peak inspiratory airway pressure, Paw = -2 cmH2O) without or with negative (approx. -5 or -10 cmH2O) or positive (approx. +5 or +10 cmH2O) inspiratory pressure, provided by a laminar flow resistance or a positive pressure source, respectively. Control measurements were performed before and after measurements with airway anesthesia. Measurements included tidal volume, respiratory frequency, ventilation, inspiratory and expiratory duration, occlusion pressure (P0.1) and end-tidal PCO2. None of the parameters measured was significantly altered by airway anesthesia, which was effective in suppressing the cough reflex. We conclude that information from lung afferents that are suppressed with the elimination of the cough reflex is not important for the breathing pattern during resting ventilation with elevated tidal volume (dead space load) and with positive or negative inspiratory pressure. PMID- 1518990 TI - Ventilatory and P0.1 response to hypercapnia in quadriplegia. AB - Unlike individuals with comparable degrees of respiratory muscle weakness from other causes, quadriplegic patients have a blunted ventilatory and P0.1 response to hypercapnia. This suggests that the diminished response in quadriplegia is due, in part, to an alteration in respiratory drive. We measured the hypercapnic response in 9 subjects with chronic quadriplegia (Q) and 8 normal controls (N). Ventilatory muscle strength, maximum voluntary ventilation (MVV), and lung volumes were measured in all subjects. The ventilatory response (HCVR) in Q was significantly less than in N (0.73 +/- 0.37 vs 2.95 +/- 0.4 L.min-1.mmHg-1; P less than 0.001), even when normalized for indices of respiratory muscle performance (e.g., vital capacity, MVV). There was no significant change in the HCVR in Q after the administration of naloxone. We also serially studied 2 subjects with acute quadriplegia, and found that despite progressive improvement in respiratory muscle performance, there was no accompanying increase in the response to hypercapnia. These data suggest that muscle weakness alone cannot explain the blunted hypercapnic response in quadriplegia, and are consistent with the hypothesis that these subjects have a reduced ventilatory drive. PMID- 1518991 TI - Collinearity diagnosis for a relative risk regression analysis: an application to assessment of diet-cancer relationship in epidemiological studies. AB - In epidemiologic studies, two forms of collinear relationships between the intake of major nutrients, high correlations, and the relative homogeneity of the diet, can yield unstable and not easily interpreted regression estimates for the effect of diet on disease risk. This paper presents tools for assessing the magnitude and source of the corresponding collinear relationships among the estimated coefficients for relative risk regression models. I show how to extend three tools (condition indices, variance decomposition proportions, and standard inflation factors) for diagnosing collinearity in standard regression models to likelihood and partial likelihood estimation for logistic and proportional hazards models. This extension is based on the analogue role of the information matrix in such analyses and the cross-product matrix in the standard linear model. I apply the methodology to relative risk models that relate crude intakes (on the log scale) and nutrient densities to breast cancer cases in the NHANES-I follow-up study. The three diagnostic tools provide complementary evidence of the existence of a strong collinearity in all models that is due largely to homogeneity of the population with respect to our risk scale for the crude intakes. The analysis suggests that the non-significant relative risks for the crude intakes in these models may be due to their involvement in collinear relationships, while the nonsignificant relative risks for the nutrient densities are far less affected by multicollinearity. PMID- 1518992 TI - Smoothing reference centile curves: the LMS method and penalized likelihood. AB - Refence centile curves show the distribution of a measurement as it changes according to some covariate, often age. The LMS method summarizes the changing distribution by three curves representing the median, coefficient of variation and skewness, the latter expressed as a Box-Cox power. Using penalized likelihood the three curves can be fitted as cubic splines by non-linear regression, and the extent of smoothing required can be expressed in terms of smoothing parameters or equivalent degrees of freedom. The method is illustrated with data on triceps skinfold in Gambian girls and women, and body weight in U.S.A. girls. PMID- 1518993 TI - Comparing in-patient classification systems: a problem of non-nested regression models. AB - Since 1983, hospitals in the United States have been receiving prospective payment for their in-hospital patient admissions covered under Medicare. Under such schemes each patient is placed in a group by a classification system, known as the Diagnosis Related Groups (DRG), and the hospital is reimbursed by the Health Care Financing Administration according to some predetermined group average, adjusted for hospital level characteristics, such as size, location and teaching activity. Recent interest has focused on refining the DRG system or considering totally different systems of classification. Studies designed to compare the ability of different systems to account for between-patient variability in resource consumption in the same dataset lead to the problem of model selection between large non-nested regressions, where resource consumption, measured by length of hospital stay or costs, is regressed on dummy-indicator variables representing different patient groups. We use a simple measure of fit to develop a symmetric test of the null hypothesis that the two systems account equally well for variability in resource consumption. With this method, unlike methods such as Akaike's AIC criterion, we can quantify the probability of a false positive, and thereby limit the probability of choosing one system over another when it is no better at accounting for variability in resource consumption. PMID- 1518994 TI - A retrospective assessment of the 75/75 rule in bioequivalence. AB - The 75/75 rule was originally proposed by the U.S. Food and Drug Administration (FDA) as an alternative means of testing the bioequivalence of two formulations of a pharmaceutical agent. The rule specified that the ratio of test-to-reference formulation of a bioavailability measure arising in a bioequivalence study must be between 75 and 125 per cent of unity in at least 75 per cent of subjects to declare two formulations bioequivalent. The rule has garnered criticism in the literature and the FDA no longer uses the rule formally in assessing bioequivalence. The basis, however, for all criticism of the rule has been simulation arguments. In this paper, we derive the sampling model implied by the rule and place the rule in the framework of a statistical hypothesis test. We show how the significance level of the test depends upon variability of the formulations, and thus why the rule performs in the way that has received criticism. PMID- 1518995 TI - Optimal checking procedures for monitoring laboratory analyses. AB - Many clinical, environmental, and epidemiologic studies rely heavily upon biochemical data, and the quality of these data is of paramount importance to the validity of study conclusions. Traditionally, far more attention has been given to the analysis of study data than has been given to monitoring the quality of the data. In this paper we draw an analogy between monitoring a laboratory system and an industrial production process and discuss the limitations of industrial quality control plans when applied in a laboratory setting. We derive methods for computing optimal checking schedules for laboratory analyses. These schedules formalize traditional laboratory practices of periodic checking and provide guidelines for the frequency and placement of checks within a finite batch of analyses. When laboratory system failure can be reasonably approximated by an exponential or geometric distribution, optimal checking schedules are relatively easy to compute. For more complex failure distributions, we present a dynamic programming approach. We describe an application to the measurement of selenium status in plasma samples using an electrothermal atomic absorption spectrophotometry procedure. PMID- 1518996 TI - Withdrawal censoring and the sequential logrank procedure. AB - The effects of withdrawal censoring on the power of the group sequential logrank procedure are examined in the context of survival studies. Special attention is given to an assumption that the withdrawal censoring mechanism is only conditionally independent of survival time. Simulation studies of two-sample, fixed duration trials, under random right censoring, staggered entry and exponential life times, reveal a general decrease in statistical power that is most pronounced when the withdrawals are unbalanced, the majority occurring in the group with the higher hazard rate. Generally, this decrease in power is not of practical concern under typical withdrawal rates except when conditional independence is present in which case large fluctuations in power and type I error rates can occur. PMID- 1518997 TI - Creation of a semiannual report for a multicentre co-operative clinical trials group. AB - The Southwest Oncology Group (SWOG) is a multicentre co-operative group that performs prospective clinical trials in cancer. The SWOG Statistical Center is responsible for preparing a report of studies for the semiannual meetings. The report includes a summary of study design and eligibility criteria, current accrual, baseline patient characteristics, toxicity, and, for studies closed to accrual and with sufficiently mature outcome data, tumour response or patient survival. A software program, Statisticians' Report Worksheet (SRW), has been developed by the programming staff at the SWOG Statistical Center. This program enables each disease specific chapter to be created independently, but ensures that tables and graphs for all chapters are of uniform style. We describe here the coordination of the report, and the use of the SRW program. This reporting system can serve as a model for other groups. PMID- 1518998 TI - Bayesian methods for phase I clinical trials. AB - Phase I clinical trials are conducted to determine the dose-response curve of a new drug with respect to toxic side effects and, in particular, to estimate the maximum tolerated dose (MTD). In this paper we take a Bayesian approach to the problem of making inferences about the MTD. Working with broad classes of priors, we obtain the posterior distribution of the MTD and study its properties. We also address the question of providing updated assessments of the risk of toxicity for new patients entering the study at a specific dose level. These assessments would be useful in deciding issues of study management and ethics. Our analysis pays particular attention to the sensitivity of the inferences and risk assessments to the choice of prior and the choice of model for the dose-response relationship. PMID- 1518999 TI - Sample size determination for group sequential clinical trials with immediate response. AB - The use function approach to group sequential methods has been explored previously. Any group sequential design requires specifying the frequency and times of repeated analyses, but only the use function approach allows deviations from those specified in the design, without affecting the type I error in the analysis. This paper illustrates how the use function provides a simple and flexible design procedure and how the initially projected maximum sample size can be calculated for randomized clinical trials in which responses are known relatively soon after patient entry and for which there is an early stopping rule built into the study protocol. Also the consequence of using the proposed design procedure is investigated in terms of the operating characteristics of the subsequent group sequential analyses. PMID- 1519000 TI - Interpretation of interaction in factorial analysis of variance design. PMID- 1519001 TI - Sleep and cardiorespiratory characteristics of infant victims of sudden death: a prospective case-control study. AB - We studied the polygraphic sleep recordings of 30 infants who eventually died of sudden infant death syndrome (SIDS) and those of 60 matched control infants. All records were extracted from 20,750 sleep studies collected prospectively in 10 sleep laboratories. Of the 30 future SIDS victims, 5 were siblings of SIDS victims and 9 were studied after an apparent life-threatening event. For each SIDS victim, two normal control infants were matched for sex, gestational age, postnatal age and weight at birth. The future SIDS infants were reported to have more frequent episodes of regurgitations after feeding (p = 0.01) and profuse sweating during sleep (p = 0.01) than the control subjects. Only two polysomnographic variables characterized the future SIDS infants. Compared to control subjects, the SIDS infants moved less during sleep (p = 0.04) and had significantly more frequent obstructed breathing events. Obstructive and mixed apneas were seen in 23 of 30 future SIDS victims, but in only 9 of 60 control subjects (p = 0.01). The obstructed and mixed apneas lasted longer in the SIDS than in the control infants (p = 0.01) but did not exceed 15 seconds. The obstructed breaths occurred mainly in rapid eye movement sleep (78% of the events) and were accompanied by drops in heart rates to 68 beats per minute and in SaO2 levels to 75%. The present report adds further indirect evidence for a possible sleep-related impairment of respiratory control in some infants who eventually died of SIDS. PMID- 1519002 TI - Wrist actigraphy in insomnia. AB - To assess the use of actigraphy in evaluating insomnia, 36 patients with a serious complaint of insomnia slept 3 nights each in the laboratory, where the usual polysomnograms (PSGs) were obtained as well as actigraphic assessments of their sleep. Patients also wore actigraphs for 7 days at home, were extensively interviewed and filled out psychometric tests. Based on all this information, the patients were then diagnosed according to the International Classification of Sleep Disorders. Averaged over the 3 nights for each insomniac, the mean discrepancy between actigram and PSG was 49 minutes per night. In three-fourths of the cases, actigram and PSG agreed to within 1 hour on the total amount of sleep per night. Discrepancies, however, were not random: In patients with psychophysiologic insomnia and in insomnia associated with psychiatric disease, the actigram typically overestimated sleep when compared with the PSG. In patients with sleep-state misperception, the actigram was either quite accurate or it underestimated sleep when compared with the PSG. Comparing laboratory with home sleep, one-third of all insomniacs slept better in the laboratory and two thirds slept better at home. In addition, night-by-night variability was higher at home than in the laboratory. Based on our study, we now recommend actigraphy as an additional tool in the clinical evaluation of insomnia, but we believe that in complex cases it should be combined with 1 PSG night in the sleep disorders center. PMID- 1519003 TI - Patients' acceptance of psychological and pharmacological therapies for insomnia. AB - This study evaluated the acceptance of psychological and pharmacological therapies among chronic insomniacs and noncomplaining good sleepers. After reading a brief written description of two treatment methods commonly used for persistent insomnia (i.e. cognitive-behavior therapy and pharmacotherapy), the subjects rated in a counter-balanced order several dimensions of these two treatment modalities. The results showed that the psychological intervention was rated as more acceptable and more suitable than the pharmacological one among both insomniacs and their noncomplaining significant others. Behavior therapy was also expected to be more effective on a long-term basis and to produce fewer side effects as well as more benefits on daytime functioning. The clinical implications and relevance of treatment acceptance in the management of insomnia are discussed. PMID- 1519004 TI - Time-of-night patterns in PLMS activity. AB - Time-of-night patterns for periodic leg movement in sleep (PLMS) activity were assessed in 72 patients diagnosed as having PLMS (46 with only PLMS, 10 with narcolepsy and PLMS and 16 with sleep apnea and PLMS). Two distinct patterns of PLMS activity were identified. For one pattern, PLMS activity was high initially upon falling asleep and then decreased across the remainder of the night with the majority of the activity occurring during the first half of the night. For the second pattern, PLMS activity was relatively evenly distributed across the night with slightly greater activity in the middle of the night. These patterns were highly reliable across two nights of recording for group 1 and less so for group 2 even though there was significant variability between nights in the number of PLMS. Patients in group 2 were younger (except for those with sleep apnea) and were sleepier during the day. Implications of these findings for pharmacologic management are discussed. PMID- 1519005 TI - Periodic limb movement disorder is associated with normal motor conduction latencies when studied by central magnetic stimulation--successful use of a new technique. AB - This study prospectively tested the hypothesis that patients with periodic limb movement disorder (PLMD) have longer motor conduction latencies than normals. Six healthy adults, 13 patients with PLMD, and 8 patients with long-term multiple sclerosis (MS) had recordings of motor conduction latencies during wake and sleep. MS subjects were included only to show that we could detect prolongation of central conduction; nonMS subjects were used to test the hypothesis. Subjects had no other medical or sleep problems. A novel magnetic stimulator, the Cadwell MES-10, was discharged over the vertex and the C7 cervical spine. It triggered compound muscle action potentials that were recorded in the abductor digiti minimi in the hand. The conduction latencies were the total conduction time (TCT), measured vertex to hand, and the peripheral conduction time (PCT), measured C7 to hand. The difference was the central conduction time (CCT). Only TCT could be obtained during sleep. Supporting the use of TCT as an indirect measure of central conduction was that, in all waking subjects, TCT correlated with CCT (r = 0.91, p = 0.001) but not with PCT. Reliabilities during wake and sleep were 0.95 or higher for TCT and PCT measurements. Waking CCT was greater in MS subjects (13.77 milliseconds) than those without MS (9.21 milliseconds), p = 0.001. Sleeping TCT was much less impressive in distinguishing MS subjects [27.08 milliseconds in nonrapid eye movement (NREM) sleep; 28.64 milliseconds in rapid eye movement (REM) sleep] from nonMS subjects (24.45 milliseconds in NREM; 24.84 milliseconds for REM), p = 0.07 for NREM and p = 0.04 for REM.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1519006 TI - Do patients with the sleep apnea/hypopnea syndrome drink more alcohol? AB - As alcohol ingestion may worsen the sleep apnea/hypopnea syndrome, we have investigated the alcohol consumption of patients with the sleep apnea/hypopnea syndrome in comparison to control subjects to determine whether patients with the sleep apnea/hypopnea syndrome drink excessively. A lifetime alcohol history was taken from each. There was no significant difference between the 50 patients with the sleep apnea/hypopnea syndrome and 95 age-matched controls in either the lifetime (patients 27, SEM 5 x 10(3); controls 26, SEM 4 x 10(3) units) or current (12, SEM 2; 12, SEM 2 units per week) alcohol consumption. There was no evidence that alcohol consumption was related to the development of arterial carbon dioxide retention or peripheral edema in such individuals. PMID- 1519007 TI - Daily social rhythms in the elderly and their relation to objectively recorded sleep. AB - This study tested the hypothesis that the impaired sleep of healthy 71-91 year olds might be due to circadian dysfunction stemming from irregularity of life style. Twenty-five old women, 20 old men and 21 young controls (19-28 years old) were studied in relation to 1) objective sleep as measured in the laboratory, 2) subjective sleep quality as measured by the Pittsburgh sleep quality index (PSQI) and 3) the social rhythm metric (SRM), an instrument to quantify the daily rhythms of life. Contrary to prediction, the SRM scales revealed that the older group had just as many activities completed and just as much other-person involvement as the young. Moreover, they showed a significantly greater regularity in daily life-style than the young, despite showing reliably impaired subjective and objective sleep. This suggests either that these seniors have always been regular in their life-style and that this has been protective of their health and vigor, or that their regularity has been developed as an adaptive response to age-related changes in the circadian system. PMID- 1519008 TI - Sleep propensity free-runs with the temperature, melatonin and cortisol rhythms in a totally blind person. AB - In previous studies, we found that many totally blind people have free-running melatonin rhythms, but that free-running melatonin rhythms were not necessarily associated with periodic insomnia and daytime sleepiness. Thus, it was not clear if the circadian sleep propensity rhythm was free-running with the other circadian rhythms. In the present study, we report that the sleep propensity rhythm (as defined by an ultrashort sleep-wake schedule) free-ran with the melatonin, temperature and cortisol rhythms in a 44-year-old totally blind man even though he maintained a conventional sleep schedule and did not complain of clinically significant insomnia or excessive daytime sleepiness. PMID- 1519009 TI - Dynamics of EEG slow-wave activity and core body temperature in human sleep after exposure to bright light. AB - In seven subjects sleep was recorded after a single 3-hour (2100-0000 hours) exposure to either bright light (BL, approx. 2,500 lux) or dim light (DL, approx. 6 lux) in a crossover design. The latency to sleep onset was increased after BL. Whereas rectal temperature before onset and during the first 4 hours of sleep was higher after BL than after DL, the time course of electroencephalographic (EEG) slow-wave activity (SWA, EEG power density in the range of 0.75-4.5 Hz) in nonrapid eye movement sleep (NREMS) differed only slightly between the conditions. After BL, SWA tended to be lower than after DL in the first NREMS REMS cycle and was higher in the fourth cycle at the time when the rectal temperature did not differ. The differences in SWA may have been due to a minor sleep-disturbing aftereffect of BL, which was followed by a rebound. The data are not in support of a close relationship between SWA and core body temperature. PMID- 1519010 TI - Sleep in human narcolepsy revisited with special reference to prior wakefulness duration. AB - Sleep of 11 narcoleptic subjects was recorded on baseline and after 16 and 24 hours of prior wakefulness (16 and 24 hours sleep deprivation). Eleven sex- and age-matched control subjects were recorded for comparisons. All recordings in narcoleptic subjects were characterized by frequent sleep onset rapid eye movement (REM) episodes, increased amounts of wake time after sleep onset and low sleep efficiencies. Mean total sleep time (TST) was significantly decreased in narcoleptic subjects after sleep deprivation (SD). Recovery sleep after 24 hours SD showed reduced nonREM (NREM) sleep stage 2 percentage, whereas percentages of stage 4 and slow-wave sleep (SWS = stages 3 + 4) were significantly increased. The values of REM sleep percentage of TST were remarkably constant throughout and did not differ significantly as a function of experimental conditions, indicating a normal REM sleep pressure in narcolepsy. Sleep stage analysis per sleep cycles revealed significant differences between the two groups. Percentages of stage 4 and SWS were increased during the first cycle of recovery sleep in narcoleptic subjects. Stage 2 was decreased during the third cycle, and SWS decreased rapidly from cycle 1 to cycle 2 and slightly increased thereafter. These results indicate that sleep need is increased in narcolepsy, whereas its decrease over the first NREM-REM cycle is accelerated. We hypothesize that this could reflect an alteration of the homeostatic process of sleep regulation in narcolepsy. PMID- 1519011 TI - Beta (20-28 Hz) and delta (0.3-3 Hz) EEGs oscillate reciprocally across NREM and REM sleep. AB - Across-night oscillations of beta (20-28 Hz) and delta (0.3-3 Hz) electroencephalograms (EEGs) were examined with spectral analysis in 10 normal young adult subjects (Ss). In each S, power densities of beta were found to oscillate reciprocally with delta power density across both nonrapid eye movement (NREM) and rapid eye movement (REM) sleep. Linear correlation coefficients between log power density of delta vs. beta were significant (p less than 0.0001) for each S. An incidental observation was that beta power within REM was reliably lower in epochs with more eye movement activity. The reciprocal relationship between beta and delta holds implications for sleep physiology and supplements our earlier finding that sigma (12-15 Hz) oscillates reciprocally with delta within NREM sleep. These descriptions of the continuously varying EEG across sleep provide information not available when EEG measures are tabulated by discrete NREM periods and REM periods. PMID- 1519012 TI - T-sleep: an improved method for scoring breathing-disordered sleep. AB - We developed a new method to score sleep fragmented by respiratory events that we call the T-sleep (transitional sleep scoring) method. Five control polysomnograms from subjects without sleep-related breathing abnormalities were scored by the Rechtschaffen and Kales (R&K) method, and 10 polysomnograms from patients with severe obstructive sleep apnea were scored by both the R&K and the T-sleep method. Comparative analyses were performed on sleep variables of the control and apnea polysomnograms, and interscorer correlations were assessed for sleep and apnea variables. The interscorer correlations were high for both R&K control scoring and for apnea recordings scored by the T-sleep method. The number of sleep stage events documented for the 10 apnea recordings was significantly less for the T-sleep method than the R&K method (36, SD 17.0 vs. 332, SD 144.0; p = 0.0002). The T-sleep method was shown to be an effective, accurate and quick method for scoring sleep in patients with sleep-related breathing disorders. PMID- 1519013 TI - Short technical note: quantification of periodic breathing: preliminary studies. AB - Although the apnea/hypopnea index is the most widely used measure of breathing pattern abnormality during sleep, this index gives no information about the strength of the oscillation in the breathing pattern, its periodicity or its regularity. Such information may be required in research studies involving breathing patterns and how they are affected by interventions. We are exploring spectral analytic methods to determine two normalized indices, the periodicity index and the modified modulation index, to examine periodic breathing for all night sleep studies. These methods are automatic and require no user interaction. Data were obtained from 11 heart failure patients who slept for a total of 21 nights in the sleep laboratory. Because individual patients had a marked regularity of their Cheyne-Stokes respiration during sleep, one would expect an extremely high correlation between the traditional measures of breathing pattern abnormality and these spectral analytic techniques. Indeed we found that there was an extremely high correlation between the periodicity index and the modulation index and the traditional measures of apnea/hypopnea index and the proportion of the night with periodic breathing (p less than 0.02 in all cases). When the breathing pattern was irregular but still with many apneas there was a discrepancy between the apnea index and the indices of periodicity. These techniques are still preliminary and future studies will determine their limitations in other patient populations and where the pattern is unstable. PMID- 1519014 TI - Removal of ocular artifacts from the REM sleep EEG. AB - The present report concerns the first study in which electrooculographic (EOG) contamination of electroencephalographic (EEG) recordings in rapid eye movement (REM) sleep is systematically investigated. Contamination of REM sleep EEG recordings in six subjects was evaluated in the frequency domain. REM-active and REM-quiet series were obtained for each subject. Transfer coefficients and power spectra of EOG and EEG indicated that (a) increases in transfer coefficients beyond 4.5 Hz are brought about by residual EEG in the EOG, and (b) EOG-EEG contamination in the delta band is most pronounced in frontal, intermediate in central and negligible in occipital leads. It was found that correction of the REM-active series resulted in significant (c) reductions in power, (d) increases in interhemispheric coherences and (e) reductions in degree of lateral asymmetry. These effects were largest for frontal leads, but still marked for central ones. The results are discussed in the light of previous findings concerning models of hemispheric functioning during REM sleep. PMID- 1519015 TI - Reliability and factor analysis of the Epworth Sleepiness Scale. AB - The Epworth Sleepiness Scale (ESS) is a self-administered eight-item questionnaire that has been proposed as a simple method for measuring daytime sleepiness in adults. This investigation was concerned with the reliability and internal consistency of the ESS. When 87 healthy medical students were tested and retested 5 months later, their paired ESS scores did not change significantly and were highly correlated (r = 0.82). By contrast, ESS scores that were initially high in 54 patients suffering from obstructive sleep apnea syndrome returned to more normal levels, as expected, after 3-9 months' treatment with nasal continuous positive airway pressure. The questionnaire had a high level of internal consistency as measured by Cronbach's alpha (0.88). Factor analysis of item scores showed that the ESS had only one factor for 104 medical students and for 150 patients with various sleep disorders. The ESS is a simple and reliable method for measuring persistent daytime sleepiness in adults. PMID- 1519016 TI - Bibliography of recent literature in sleep research. PMID- 1519017 TI - Membrane-bound catechol-O-methyltransferase: a reevaluation of its role in the O methylation of the catecholamine neurotransmitters. PMID- 1519018 TI - Adaptation of mammalian skeletal muscle fibers to chronic electrical stimulation. PMID- 1519019 TI - The influence of buffalo and bovine serum on transformation of Trypanosoma congolense from metacyclic forms to bloodstream forms in vitro. AB - The transformation of Trypanosoma congolense metacyclics into bloodstream forms was studied in vitro using light and electron microscopy. The trypanosomes were maintained in culture at 28 degrees C using a medium supplemented with foetal bovine serum. The metacyclics were harvested and separated from the procyclic and epimastigote forms by using anion exchange chromatography. Isolated metacyclics were incubated with different concentrations of buffalo or bovine serum at 35 degrees C for periods ranging from 3 hours to 72 hours. It was noted that the metacyclics transformed at about the same time regardless of the animal serum used. However, most of the buffalo serum tended to kill trypanosomes whereas bovine serum tended to support trypanosome growth. The killing of the trypanosomes may be due to natural toxins present in buffalo serum. PMID- 1519020 TI - Chemotherapy of CNS-trypanosomiasis: the combined use of diminazene aceturate or pentamidine with DL-alpha-difluoromethylornithine (DFMO). AB - The chemotherapy of CNS-trypanosomiasis with DL-alpha-difluoromethylornithine (Eflornithine, DFMO) with the diamidine, pentamidine (Lomidine) or diminazene aceturate (Berenil) was examined using the mouse model for CNS-trypanosomiasis. Although combined DFMO/pentamidine therapy can give complete cures, one or more doses of 100 mg/kg pentamidine was required with continuous administration of DFMO for 14-16 days, and even this treatment failed to cure the mice in a repeat experiment. Diminazene aceturate was more efficient and provided a 40 mg-kg dose was utilised, it was possible to reduce the period of DFMO to approximately 12 days. Attempts to reduce the dose rate of diminazene to less than 40 mg-kg failed. Of the two compounds, diminazene aceturate was the more successful and could possibly be used in combination with DFMO in the treatment of CNS trypanosomiasis. PMID- 1519021 TI - Pharmacomodulations on new organometallic complexes of Ir, Pt, Rh, Pd, Os: in vitro and in vivo trypanocidal study against Trypanosoma brucei brucei. AB - New organometallic complexes have been synthesized by association of an active organic molecule with a metallic element such as Pt, Rh, Ir, Pd, Os. Their trypanocidal activity was studied in vitro and in vivo against T. b. brucei. The more active compounds were pentamidine derivatives. The Ir- COD-pentamidine complex, and Iridium (I) cationic and organometallic complex showed and in vitro activity at 60 micrograms/l. Moreover, all infected mice were cured by this compound subcutaneously administered in a single dose at 0.5 mg/kg (0.317 mumol/kg). In the same conditions, pentamidine cured all the mice at 5 mumol/kg. Ir-COD-pentamidine (or P1995) was 16 fold more efficient than pentamidine. Since the chemotherapeutic index of this molecule was 7.5 fold higher than those of pentamidine, P1995 can be considered as a potential trypanocidal drug of the future. PMID- 1519022 TI - Experimental infection of Friesian Holstein calves with an Indonesian isolate of Trypanosoma evansi. AB - The effect of a single, primary, artificial infection with Trypanosoma evansi was studied in nine Friesian Holstein calves. Body temperature, packed cell volume (PCV) and parasitaemia measurements were obtained daily from each of the infected calves for up to 90 days after parasites were injected, body weights were monitored weekly. T. evansi infection had a marked depressive effect on PCV profiles and the rate of body weight gain. PMID- 1519023 TI - Proposals for a new therapeutic strategy for simple Plasmodium falciparum malaria attacks in Cameroon. AB - From simplified in vivo tests, authors set up a cartography of the sensitivity of Plasmodium falciparum to amino-4-quinolines in Cameroon; they also evaluated the clinical and parasitological efficacy of different therapeutic protocols which make use of amino-4-quinolines, quinine, mefloquine and halofantrine. All these drugs are administered orally. They recommend maintaining home medication with chloroquine at the dose of 25 mg/kg over 3 days, conserving quinine for use in the case of a possible failure. The use of most recent antimalarials can be proposed only as a last resort. PMID- 1519024 TI - The prevalence of trachoma in preschool and school children in Olimpia, Guaraci and Cajobi, Sao Paulo, Brazil. AB - A school-based prevalence survey of trachoma was conducted in three rural municipalities in the state of Sao Paulo, Brazil, in 1989. A total of 950 children aged 4-11 years were examined. The prevalence of inflammatory trachoma was found to be 6.3%, peaking at 24.1% in the 4 year-old age group. The prevalence of trachomatous scarring was 2.7% and was more prevalent in older children. Risk factors included household sleeping arrangements and nasal discharge. PMID- 1519025 TI - Evaluation of a simple screening test for the quality of drinking water systems. AB - A simple and inexpensive assay for detection of H2S producing bacteria in drinking water was evaluated in Paraguay. Using an improved preparation procedure, results were basically temperature independent in the range of 22-37 degrees C and correlated well with the presence of total coliform bacteria (96%, 28 degrees C). The assay was not suitable for control of surface water and dug well water due to the frequent presence of non-faecal coliforms. However, it was very suitable for routine control of high quality water systems, like treated community water systems or deep-tube well water, where complete absence of coliforms is required. The H2S-test is very inexpensive and does not require a laboratory technician or special equipment. Its use permits a cost-effective routine control of high quality community water systems in developing countries. In addition, this test turned out to be an effective educational tool for heightening the awareness of people towards dangers of unclean drinking water. PMID- 1519026 TI - Cutaneous myiasis caused by tumbu fly larvae, Cordylobia anthropophaga in southwestern Saudi Arabia. AB - Seven cases of human cutaneous myiasis caused by maggots of the tumbu fly, Cordylobia anthropophaga are reported from Asir region, southwestern Saudi Arabia. Boil-like swellings infested with individual fly larvae, varied from one to four and occurred in both unprotected and usually protected areas of the skin. Twenty five fly maggots were retrieved from separate furunculoid lesions on the body surface of a massive case of a 4-year old boy. The present observations confirm that this calliphorine species is not restricted to tropical Africa. PMID- 1519027 TI - Differential recognition of Dirofilaria immitis antigens by human IgG and IgM positive sera. Preliminary data based on EITB analysis. AB - Preliminary data are presented on the differential recognition of Dirofilaria immitis antigens by sera positive for IgG and IgM (detected by enzyme linked immunosorbent assay, ELISA) using the enzyme-linked immunoelectrotransfer technique (EITB). The sera were followed prospectively over a year to detect seasonal variations. IgG mainly recognized antigens with a molecular weight (MW) lower than 74 kDa, while IgM recognized those with a MW higher than 43 kDa. The antigens with MW between 74 and 61 kDa were recognized by both isotypes. In IgG positive sera all bands were recognized throughout the year, albeit more mildly in summer. For IgM it is noteworthy that antigens with a MW between 43 and 20 kDa were not recognized in spring. These data are in accordance with those obtained with ELISA in the seasonal follow-up of positive sera. PMID- 1519028 TI - IgA immunoassay for the diagnosis of bancroftian filariasis. AB - In some parasitic infection such as toxoplasmosis, specific IgA is a highly reliable marker of active infection. In bancroftian filariasis, only 10 of 20 (50%) and 3 of 20 (15%) of the microfilaremic patients were positive for IgA anti Brugia malayi using respectively indirect ELISA and immunocapture ELISA tests. As regard to these low sensitivities, the detection of specific IgA is unlikely to be a useful test for the diagnosis of active Wuchereria bancrofti infection. PMID- 1519029 TI - Ocular onchocerciasis and the intensity of infection in the community. IV. The degraded forest of Sierra Leone. AB - To assess the pattern of onchocercal ocular disease and blindness in south Sierra Leone, ophthalmological surveys were carried out in 13 highly infected villages located in various river basins. The most important finding was the blinding potential of onchocerciasis in the degraded forest area where the prevalence of onchocercal blindness reached levels of up to 6%. This is remarkable since previous studies have claimed onchocerciasis in the forest to cause little blindness. Ocular onchocerciasis undoubtedly constitutes a problem of public health importance in south Sierra Leone. The rates of onchocercal ocular disease and blindness, however, were significantly lower than those found in savanna villages with similar levels of endemicity. The community pattern of ocular onchocerciasis was not significantly different from the classical pattern in the forest but this could be explained by the low endemicity levels in the forest villages studied. It is therefore not possible to deduce from this study whether the pattern of ocular onchocerciasis in south Sierra Leone is of the forest type, or a pattern on its own. PMID- 1519030 TI - Onchocerciasis prevalence in previously known foci in western Uganda: results from a preliminary survey in Kabarole district. AB - A prevalence survey of onchoceriasis was done in Kabarole district, Uganda, in 1990. The objective was to determine the prevalence of onchocerciasis among communities living in previously known foci. A total number of 1186 persons was included in the study. The infection rate among the communities studied ranged from 0% to 67%. The most frequent clinical signs and symptoms of onchocerciasis were: pruritus (80%), rough skin (46%), skin rash (30%), leopard skin (6%) and sclerosing keratitis (7%). 3.6% of all cases with onchocercasis were found to have no perception of light. The total number of cases in the district was estimated to be 32,000. The study showed that the foci, where Simulium neavei is the vector, are still active. In contrast, very few infections with Onchocerca volvulus were found in the Rwenzori focus, where S. damnosum s. 1. was the vector. The results indicate that onchocerciasis is of public health importance in Kabarole district and needs to be controlled. PMID- 1519031 TI - Compared efficacy of repeated annual and semi-annual doses of ivermectin and diethylcarbamazine for prevention of Wuchereria bancrofti filariasis in French Polynesia. Final evaluation. AB - In October 1989, 58 apparently healthy Polynesian Wuchereria bancrofti carriers, in whom microfilarial (mf) density was greater than or equal to 100 mf/ml, were randomly allocated to treatment groups receiving single doses of either ivermectin at 100 mcg/kg or diethylcarbamazine (DEC) at 3 and 6 mg/kg. Six months later, half of the carriers initially treated with ivermectin 100 mcg/kg or DEC 3 mg/kg were given a second similar dose while the rest were given a placebo. Six months later again, all of the carriers received a last treatment dose similar to the initial one. The results observed during the 12-month period which followed this last treatment have confirmed that (i) in terms of immediate clearance or complete negativation of microfilaremia, the efficacy of ivermectin is higher than that of DEC (at dosage of 3 or 6 mg/kg), (ii) DEC is more effective than ivermectin in sustaining the reduction of microfilaremia over a longer period of time and (iii) the efficacy of repeated single doses of either DEC 3 mg/kg or ivermectin 100 mcg/kg is much higher when given semi-annually than annually.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1519032 TI - In vitro and in vivo effect of diethylcarbamazine on the activity of acetylcholinesterase from Wuchereria bancrofti infected human serum. AB - The acetylcholinesterase (AChE) activity was measured in human serum from persons infected with the filarial parasite Wuchereria bancrofti. The asymptomatic microfilaremic serum showed five times increase in AChE-activity as compared with normal serum, whereas only little difference was observed in serum from patients with elephantiasis. Similar results were obtained when the enzyme activity was measured in the immune complexes precipitated with polyethyleneglycol. Further, the effect of the antifilarial drug diethylcarbamazine (DEC), on the AChE activity of infected and normal serum was studied in in vivo and in vitro experiments. In vitro, DEC was found to be effective only with respect to AChE from asymptomatic microfilaremic serum where 75% decrease in enzyme activity was observed at 100 mumol. The oral administration of DEC (5 mg/kg of body weight/day) effected the activity of AChE from microfilaremic serum as shown after 1 hr, 1 and 3 weeks. A regular decrease in enzyme activity of asymptomatic microfilaremic serum was observed. By increasing time periods and after three weeks the level of AChE reaches the normal value. In vitro and in vivo the same concentration of DEC has negligible effect on the normal serum suggesting that in case of asymptomatic microfilaremic serum the increased activity of AChE is different in nature than the host acetylcho-[abstract incomplete in journal] PMID- 1519033 TI - Biological control of the snail intermediate hosts of Schistosoma mansoni in Martinique, French West Indies. AB - In Martinique water-cress beds constituted the last transmission sites for schistosomiasis. The competitor snail, Melanoides tuberculata, was introduced at the beginning of 1983 to a group of water-cress beds and eliminated the snail hosts, Biomphalaria glabrata and B. straminea, in less than two years. Following this first success, M. tuberculata was introduced to the other groups of beds which were inventoried at the beginning of the eighties. At the present time, B. glabrata and B. straminea have totally disappeared from eight sites and only a few individuals have been recorded from 12 sites. The two remaining water-cress beds have dried up and were abandoned. PMID- 1519034 TI - Antibodies against secreted and non-secreted antigens in mice after infection with live Mycobacterium tuberculosis. AB - Mice from four different inbred strains were infected with live Mycobacterium tuberculosis and the immune response to M. tuberculosis was followed for 24 weeks, using Western blotting. Nearly all mice, irrespective of H-2 type, reacted with the 38-kDa protein band. Antibodies against this secreted 38-kDa protein were the first to appear, 4 weeks after infection. Thereafter the secreted 19-kDa protein and non-secreted antigens, such as the 65-kDa and 33-kDa proteins, were recognized. The immune response against the non-secreted antigens was influenced by the mouse strain. However, the 33-kDa protein band was recognized by all mouse strains after a second injection with live M. tuberculosis. The specificity of the antibodies was analysed in Western blot using sonicates of M. tuberculosis, M. kansasii, M. avium, M. terrae, M. gordonae and Escherichia coli. Antibodies against the 38-kDa and 33-kDa protein bands seemed to be specific for M. tuberculosis, while antibodies against the 19-kDa protein band showed limited cross-reactivity. Antibodies against the 65-kDa protein were strongly cross reactive. These results suggest that the 38-kDa protein is secreted in vivo and, therefore, may be available to the humoral immune system at an early stage of infection. The non-secreted 33-kDa protein is only recognized by all mouse strains after prolonged contact with M. tuberculosis. PMID- 1519035 TI - The effects of deoxyspergualin on the development of diabetes in diabetes-prone BB rats. AB - The effects of the administration of the recently discovered immunosuppressant 15 Deoxyspergualin (DSP) on the development of insulin-dependent diabetes mellitus (IDDM) in diabetes-prone BB rats were studied. The data show that 2 mg/kg body weight DSP, administered six times a week from the 30th day up to the 105th day of age, significantly reduced the incidence of diabetes in diabetes-prone BB rats as compared with the PBS-injected controls. The drug was also able to reduce the signs of pancreatic insulitis and the percentages of W3/25+ and OX6+ splenocytes. Interruption of the treatment resulted in a later onset of diabetes in a high percentage of animals within 41 days. These findings suggest that 15-DSP may temporarily reverse the pathogenic mechanisms leading to beta cell destruction and autoimmune diabetes in a well-known experimental model of human insulin dependent diabetes mellitus. PMID- 1519036 TI - Involvement of interleukin-2 and interferon-gamma in the immune response induced by influenza virus iscoms. AB - Splenocytes from mice primed with influenza virus envelope proteins incorporated in iscoms, as micelles or as infectious virus, were restimulated in vitro with the same antigen. Interleukin-2 (IL-2) and interferon-gamma (IFN-gamma) were assayed in the supernatants of such cultures. Influenza virus iscoms induced IL-2 and IFN-gamma responses in restimulation experiments that were antigen specific and significantly higher than those induced by micelles or infectious virus. Serum samples collected at the end of the experiments were analysed for the antibody response and profile. The antibody titres induced by iscoms were of a similar order of magnitude as those induced by infectious virus, and were about 18 times higher than the titres induced by micelles. In mice immunized with iscoms or infectious virus the most abundant antibodies were of the IgG1 and IgG2a isotype, and the IgE response was low. We conclude that immunization with iscoms stimulates the Th1-like subtype of murine T lymphocytes. PMID- 1519037 TI - Alteration in T cell/macrophage ratio may reveal lymphocyte proliferation specific for the triggering antigen in reactive arthritis. AB - It has previously been shown that synovial fluid (SF) mononuclear cells (MNC) from patients with reactive arthritis (ReA) and some patients with undifferentiated oligoarthritis (UOA) respond specifically to the triggering bacterium (specific responders). However, in some patients there is a response to two or more bacteria (non-specific responders) and in a third group no response is found (non-responders). We assessed whether the proportion of synovial MNC which were macrophage-monocyte (MaMo) differed among the specific responder, non specific responder and non-responder groups. There was no difference between the specific (33 +/- 9) and the non-specific (32 +/- 26) groups; non-responders had a higher percentage of MaMo (61.3 +/- 31%) although the difference was not significant. We also investigated whether the specificity of the response to antigen in ReA or UOA SF was altered by changing the T-cell/MaMo ratio. In all five specific responders the immune response remained specific whatever the ratio tested. However, four of the five non-specific responders, but none of the non responders, developed a specific response to one of the tested antigens by increasing the T cell/MaMo ratio. We conclude that in some patients with a non specific response, alteration of the T cell/MaMo ratio uncovers a specific response which may identify the triggering antigen. PMID- 1519038 TI - Unusual sequence of immunoglobulin L-chain rearrangements in a gamma heavy chain disease patient. AB - Patients with gamma heavy chain disease (gamma-HCD) generally produce incomplete immunoglobulin (Ig) gamma-heavy chains (gamma-HCD protein) which cannot associate with light chains (IgL). In most patients Bence Jones proteins (BJP) are not observed. However, in the 61-year-old patient WIN we found gamma l-HCD proteins and lambda BJP in serum and urine. WIN gamma l-HCD protein does not carry the Ig Fd region, has a molecular weight of 33.5 kDa, and the seven N-terminal amino acid residues are not translated from any of the known immunoglobulin heavy chain (IgH) gene sequences. These residues are followed by the C gamma l-hinge region. In DNA from peripheral blood lymphocytes of patient WIN we found bands representing dominant rearrangements in one of the two alleles of the IgH, Ig kappa and Ig lambda locus. Taken together, the data from protein and DNA analysis strongly suggest, albeit do not formally prove, that one dominant B-cell clone which carries a rearranged and a non-rearranged allele of each Ig locus produces gamma-HCD protein and lambda BJP. The productive lambda-gene rearrangement in this clone thus has not been preceded by abortive rearrangements in both kappa locus alleles. Lymphocytes with an unusual sequence of IgL-chain gene activation seem to be involved in the case of gamma-HCD described here. PMID- 1519039 TI - Immunohistology of joint inflammation induced in rats by cell wall fragments of Eubacterium aerofaciens. AB - After a single intraperitoneal injection of cell wall fragments of Eubacterium aerofaciens, a main resident from the human intestinal flora, an acute arthritis develops within 2 days which is followed by a chronic arthritis that lasts at least 90 days. In an earlier report the histological appearance of the joint inflammation during this period has been described. In this study we investigated in more detail the cell types that are involved in the development of arthritis by using cell-type-specific monoclonal antibodies in an immunohistological assay. In the acute phase of arthritis, T-helper cells appeared in the synovial tissue together with ED1-positive (ED1+) and ED3-positive (ED3+) macrophages. After a temporary decline at day 12 all macrophage subsets, as well as T-helper cells, reappeared or increased again at day 33. Later, in the chronic phase (days 47 90), an increased number of ED1-positive (ED1+) cells in the synovial tissue and a decreased number of ED2-positive (ED2+) cells in the synovial lining was the most prominent finding when compared with control rats. These results indicate that, apart from T lymphocytes, macrophages also play an important role in the development and continuation of chronic arthritis in this model. PMID- 1519040 TI - Deafferentation pain after spinal cord injury. Part II. Management. PMID- 1519041 TI - Moving Out Services for Education and Support (MOSES): a model program for individuals with spinal cord injury. AB - A comprehensive educational, social, and community integrated program for individuals with spinal cord injury (SCI) was established at Mount Sinai Medical Center. The need for this program was evident from patients' responses to mailed questionnaires and staff's direct observations of the difficulties encountered by SCI patients when they left the hospital's protected environment and began to cope with living in their communities. The program, Moving Out Services for Education and Support (MOSES), provides relevant information and support to individuals with spinal cord injury as they make the transition from patient to community member. The goal of the program is to foster independence and initiative and to develop leadership skills which enhance successful community reintegration. This article describes the program development, content and training requirements for implementation of these services. PMID- 1519042 TI - Informed consent. PMID- 1519043 TI - Experiments on the effects of several factors on the 1-hydroxypyrene level in human urine as an indicator of exposure to polycyclic aromatic hydrocarbons. AB - The concentration of 1-hydroxypyrene in human urine was determined in six volunteers who lived under the same conditions. Samples were collected four times per day for three consecutive days; the maximum concentration of 1-hydroxypyrene was found in the samples collected late in the evening (21:00-23:00 h) which is the time recommended as suitable for determination of urinary 1-hydroxypyrene for the purpose of evaluating human exposure to polycyclic aromatic hydrocarbons (PAHs). Statistical tests show that the influence of sex, age, and smoking on urinary 1-hydroxypyrene is statistically insignificant. PMID- 1519044 TI - Hydrocarbons and fatty acids in surficial sediments (French Mediterranean coastal zones). AB - A detailed study has been made of hydrocarbons and fatty acids in nine surficial Mediterranean sediments. The hydrocarbon concentrations are generally low. The nature and the distribution of the hydrocarbons found in these sediments indicate that they originate from several different sources (terrestrial, biogenic, pyrolytic) and petroleum inputs are usually not the main source of hydrocarbons. Fatty acid concentrations vary in the range 2-52 mg.kg-1 dry sediment. Fatty acid distributions, between C14 and C20 show the biogenic autochthonous inputs. Branched and cyclopropanic fatty acids reflect a bacterial origin. These distributions are markedly different in oxic and anoxic sediments. PMID- 1519045 TI - Strengthening the Montreal protocol: does it cool down the greenhouse? AB - Strengthening of the Montreal Protocol is recently being negotiated in London in 1990 in order to achieve further reductions of the regulated CFCs and to include possibly more substances. In this article the implications of different policies with respect to control of ozone depleting substances for climate change are analysed, including the proposed substitution by HCFCs and HFCs, carbon tetrachloride and methylchloroform. A special halocarbon module was developed within the framework of RIVM's Integrated Model to Assess the Greenhouse Effect (IMAGE). IMAGE is a parameterized science based policy model and has been developed to give policy agencies a concise overview of the quantitative aspects of the greenhouse problem, to evaluate various policy options concerning climate change and to serve as a means of communication. It is concluded, from simulations with the halocarbon module, that it is of primary importance to achieve a further reduction of the regulated CFCs compared to the Montreal Protocol with compliance by as many countries as possible. From the perspective of the greenhouse effect the inclusion of longer lived halocarbons, such as carbon tetrachloride and HCFC-22 in the protocol comes second. The application of methylchloroform, halons and HCFCs and HFCs with lower global warming potentials (GWPs) than HCFC-22 contributes only marginally to the greenhouse effect in comparison with the much more important greenhouse gases carbon dioxide, methane, ozone and nitrous oxide. Especially if further growth of the total production of HCFCs after complete replacement of the present CFCs can be avoided by using these alternatives with a lower GWP, these substances could therefore be tolerated in a transition period, from the perspective of global warming. PMID- 1519046 TI - The isotopic composition of lead in man and the environment in Finland 1966-1987: isotope ratios of lead as indicators of pollutant source. AB - The isotopic composition of lead was determined in samples collected between 1966 and 1987, mainly from the Helsinki area, in emission sources (gasoline, incinerator and lead smelter emissions, coal), air, in samples representing long term deposition (lichen, soil, lake sediments), and in human tissue. Isotope ratios were determined by thermal ionization mass spectrometry after chemical separation of lead by anion exchange and cathodic electrodeposition. The origin of lead in man and the environment in the Helsinki area was evaluated by using the differences in the measured isotope ratios as an indicator. The mean of the ratio in gasoline (206Pb/207Pb 1.124 +/- 0.026) and the ratios in other emission sources in Helsinki (1.149-1.226) were significantly different. However, the wide range of isotope ratios in gasoline (1.063-1.173) reduced the accuracy when assessing the contribution of the different sources. Lead in air samples from Helsinki (1.123 +/- 0.013) could be attributed to gasoline, as could lead in soil near a highway (1.136 +/- 0.003). By contrast, isotope ratios measured in lichen (1.148 +/- 0.006) indicated considerable amounts of lead from sources with higher 206Pb abundances, evidently industrial sources. The isotope ratios in human liver, lung, and bone from individuals dying between 1976-79 (206Pb/207Pb ratio 1.142 +/- 0.015, 1.151 +/- 0.011, and 1.156 +/- 0.013, respectively) reflect the large lead emissions from the incinerators and lead smelters in the Helsinki area in the 1960s and 1970s. In lake sediment cores a correlation was found between the isotope ratios, lead concentration, and depth. The nonanthropogenic lead of high isotope ratios from bedrock was the major component at depths dated older than 100 years. At the surface of the sediment atmospheric lead prevailed, with ratios similar to those of gasoline, air samples and lichen. In the post-1900 layers, anthropogenic lead made up about 40-95% of the total sedimentary lead. PMID- 1519047 TI - Distribution, accumulation and depuration of administered lead in adult honeybees. AB - In this study the Pb concentration in honeybees was determined by graphite furnace AAS after peroral administration of PbCl2. The Pb concentration, expressed on a dry weight base was determined in relation to the distribution over the body, the accumulation time, the clearance and the exposure dose. Pb is concentrated in the digestive system with the midgut accounting for 67% and the rectum for 27% of the accumulated metal. The barrier function of this system is thus corroborated in honeybees. Pb accumulation happens slowly in young bees which feed mainly on pollen; once they switch from pollen to nectar there is a sharp rise in their Pb content. After the 26th day a limit of tissue accumulation seems to be reached. Pb accumulation is equally efficient when the contamination starts at a forager age. Pb clearance is slower than expected; after 12 days only one third of the initial lead burden has been cleared. The Pb concentration in the animals increases significantly with the Pb concentration in the sugar syrup which they are fed, except at the highest dose of 50 mg/l. The possible use of honeybees as biomonitors for Pb pollution seems promising from these results. PMID- 1519049 TI - Exclusive academies. PMID- 1519048 TI - GenPharm's knockout mice. PMID- 1519050 TI - Fetal tissue supply. PMID- 1519051 TI - Cracks in the Ivory Tower. PMID- 1519053 TI - Dingell launches a new investigation. PMID- 1519052 TI - Oregon becomes a test case for health care reform. PMID- 1519055 TI - 1-800-AIDS-NIH. PMID- 1519054 TI - How to sample the world's genetic diversity. PMID- 1519056 TI - The wide world of geography turns in Washington. PMID- 1519057 TI - Awakenings ... UV light and HIV gene activation. PMID- 1519058 TI - Chemical society hosts biotech gathering. PMID- 1519059 TI - Specification of subunit assembly by the hydrophilic amino-terminal domain of the Shaker potassium channel. AB - The functional heterogeneity of potassium channels in eukaryotic cells arises not only from the multiple potassium channel genes and splice variants but also from the combinatorial mixing of different potassium channel polypeptides to form heteromultimeric channels with distinct properties. One structural element that determines the compatibility of different potassium channel polypeptides in subunit assembly has now been localized to the hydrophilic amino-terminal domain. A Drosophila Shaker B (ShB) potassium channel truncated polypeptide that contains only the hydrophilic amino-terminal domain can form a homomultimer; the minimal requirement for the homophilic interaction has been localized to a fragment of 114 amino acids. Substitution of the amino-terminal domain of a distantly related mammalian potassium channel polypeptide (DRK1) with that of ShB permits the chimeric DRK1 polypeptide to coassemble with ShB. PMID- 1519061 TI - Target enzyme recognition by calmodulin: 2.4 A structure of a calmodulin-peptide complex. AB - The crystal structure of calcium-bound calmodulin (Ca(2+)-CaM) bound to a peptide analog of the CaM-binding region of chicken smooth muscle myosin light chain kinase has been determined and refined to a resolution of 2.4 angstroms (A). The structure is compact and has the shape of an ellipsoid (axial ratio approximately 2:1). The bound CaM forms a tunnel diagonal to its long axis that engulfs the helical peptide, with the hydrophobic regions of CaM melded into a single area that closely covers the hydrophobic side of the peptide. There is a remarkably high pseudo-twofold symmetry between the closely associated domains. The central helix of the native CaM is unwound and expanded into a bend between residues 73 and 77. About 185 contacts (less than 4 A) are formed between CaM and the peptide, with van der Waals contacts comprising approximately 80% of this total. PMID- 1519060 TI - Controlling cardiac chaos. AB - The extreme sensitivity to initial conditions that chaotic systems display makes them unstable and unpredictable. Yet that same sensitivity also makes them highly susceptible to control, provided that the developing chaos can be analyzed in real time and that analysis is then used to make small control interventions. This strategy has been used here to stabilize cardiac arrhythmias induced by the drug ouabain in rabbit ventricle. By administering electrical stimuli to the heart at irregular times determined by chaos theory, the arrhythmia was converted to periodic beating. PMID- 1519062 TI - Deactivation of visual transduction without guanosine triphosphate hydrolysis by G protein. AB - G proteins couple receptors to their target enzymes in many signal transduction cascades. It has generally been thought that deactivation of such cascades cannot occur without the hydrolysis of guanosine triphosphate (GTP) by G protein. This requirement has now been reexamined in both vertebrate and invertebrate phototransduction. Results indicate that GTP hydrolysis is not required for deactivation. Evidence is presented for an alternative model in which the target enzyme is deactivated by an inhibitory factor that is available even when GTP hydrolysis is blocked. PMID- 1519063 TI - Requirement for the adenovirus type 9 E4 region in production of mammary tumors. AB - Oncogenic viruses demonstrating a strict tropism for the mammary gland provide special opportunities to study the susceptibility of this tissue to neoplasia. In rats, human adenovirus type 9 (Ad9) elicits mammary fibroadenomas that are similar to common breast tumors in women, as well as phyllodes-like tumors and mammary sarcomas. By constructing recombinant adenoviruses between Ad9 and Ad26 (a related nontumorigenic virus), it was shown that the Ad9 E4 region was absolutely required to produce these mammary tumors. This indicates that an adenovirus gene located outside the classic transforming region (E1) can significantly influence the in vivo oncogenicity of an adenovirus. Consistent with a direct role in mammary gland oncogenesis, the Ad9 E4 region also exhibited transforming properties in vitro. Therefore, the Ad9 E4 region is a viral oncogene specifically involved in mammary gland tumorigenesis. PMID- 1519064 TI - SV2, a brain synaptic vesicle protein homologous to bacterial transporters. AB - Synaptic vesicle protein 2 (SV2) is a membrane glycoprotein specifically localized to secretory vesicles in neurons and endocrine cells. As a first step toward understanding the function of SV2 in neural secretion, a rat brain complementary DNA (cDNA) that encodes SV2 was isolated and characterized. Analyses of this cDNA predict that SV2 contains 12 transmembrane domains. The NH2 terminal half of the protein shows significant amino acid sequence identity to a family of bacterial proteins that transport sugars, citrate, and drugs. Expression of the SV2 cDNA in COS cells yielded a high level of SV2-like immunoreactivity distributed in a reticular and punctate pattern, which suggests localization to intracellular membranes. Its localization to vesicles, predicted membrane topology, and sequence identity to known transporters suggest that SV2 is a synaptic vesicle-specific transporter. PMID- 1519065 TI - Inhibition of long-term potentiation by NMDA-mediated nitric oxide release. AB - Activation of N-methyl-D-aspartate (NMDA) receptors before tetanic stimulation blocks long-term potentiation (LTP) in the CA1 region of the hippocampus. This NMDA-mediated inhibition of LTP can be reversed by the nitric oxide (NO) inhibitors L-NG-monomethyl-arginine or hemoglobin and mimicked by sodium nitroprusside. These results indicate that the timing of NO release relative to high-frequency activation of CA1 synapses may be an important determinant of LTP generation and suggest that NO may play a positive or negative modulatory role in LTP depending on prior events at the tetanized synapse and the ambient concentration of excitatory amino acids. PMID- 1519066 TI - Modulation of neural stereoscopic processing in primate area V1 by the viewing distance. AB - Accurate binocular depth perception requires information about both stereopsis (relative depth) and distance (absolute depth). It is unclear how these two types of information are integrated in the visual system. In alert, behaving monkeys the responsiveness of a large majority of neurons in the primary visual cortex (area V1) was modulated by the viewing distance. This phenomenon affected particularly disparity-related activity and background activity and was not dependent on the pattern of retinal stimulation. Therefore, extraretinal factors, probably related to ocular vergence or accommodation, or both, can affect processing early in the visual pathway. Such modulations could be useful for (i) judging true distance and (ii) scaling retinal disparity to give information about three-dimensional shape. PMID- 1519067 TI - [Locked rotational dislocation of the cervical spine]. AB - There is no generally accepted treatment protocol for dislocations of single articular processes of the cervical spine. However, the data in our own series and a survey of the literature show that in this type of injury the primary diagnosis rate is low (around 50%), that closed reduction maneuvers can be neurologically hazardous, and that operative fusion prevents certain complications. Among the 20 patients treated at the authors' institution the injury was located in the lower cervical spine in all but one patients and it was caused by a high-speed traffic accident in 14 patients. Four patients had no therapy at all; the others were fused by an anterior approach in 8, a dorsal approach in 6, and a combined method in 2 patients. There was one death due to intimal tearing of a vertebral artery. Closed reduction caused a transient neurological lesion in 2 patients. In 6 patients whose dislocation was neither reduced nor fused, 3 developed chronic instability. In our new treatment protocol dislocation of a single articular process is only reduced after a diskectomy to prevent extrusion of the disc. If reduction from the anterior approach fails or if it cannot be achieved due delayed treatment, the entrapped nerve root is decompressed. Fusion of the injured segments is carried out by bone blocks and plates or hooks. PMID- 1519068 TI - [Emergency diagnosis of sternum fracture with ultrasound]. AB - Fractures of the sternum often are not discernable on X-rays. The standard lateral X-ray of the sternum may allow the diagnosis. The aim of this study was to find out whether sternal fractures can be visualized by ultrasound. The flat, plane and broad bone provides an ideal rest for a linear scanner; the one used in our study had 5 MHz. We show that sternal fractures can easily be diagnosed by means of ultrasound, and because of an interruption of the cortical reflex, possibly better than on radiographs. We also wanted to show whether sonography, which is in widespread use for the diagnosis of blunt abdominal trauma, can also be used in an emergency situation of blunt thoracic injury (e.g. seat belt injury). In 16 cases of fractures of the sternum already diagnosed by X-ray, an examiner unacquainted with the X-ray results was able to locate and diagnose all fractures by ultrasound within 1 min. PMID- 1519069 TI - [What modifies the outcome of abdominal trauma? An analysis of 558 patients]. AB - A consecutive series of 558 patients with abdominal trauma were treated at "Bergmannsheil" Trauma Center in Bochum between 1974 and 1989. The most common patient group was traffic casualties with an age of up to 30 years a total of 218 (31.1%) patients underwent surgery, in which can the diagnosis was made only by surgeons. Isolated injuries were predominantly in the spleen (33%), liver (29%), mesenterium (16.1%), bowel (14.2%), and bladder and urethra (10.1%). Eighty-three of the patients who were operated on had multiple intra-abdominal injuries; 208 (37.3%) patients were included with polytrauma. Despite the increasing number of patients with multiple injuries mortality decreased from 27.1% between 1974 and 1979 to 19.7% between 1980 and 1989. This emphasizes the progress that has been made in diagnostic methods, surgical intensive care and the improved education of trauma surgeons. PMID- 1519070 TI - Conventional radiography and CT examination of pelvic ring fractures. A comparative study of 90 patients. AB - In a retrospective study, we compared the interpretation of conventional X-ray films of the pelvis and the CT images for 90 patients who were treated in our department for a pelvic ring fracture and who had a CT examination between January 1987 and December 1990. The conventional X-ray films and CT scans were interpreted independently by a team of two surgeons and one radiologist. Following Dunn, Berry and Connally, we classified the CT images as very helpful, quite helpful or no help at all. Only 52 of 105 (49.5%) existing bony or ligament lesions of the pelvic ring were recognized in routine X-ray films; 11 of them resulted in a false diagnosis. In 14 cases important additional information about the associated-soft tissue lesions was acquired. In the same CT session, 30 additional CT examinations were performed. Using the Dunn, Berry and Connally classification, only 18 (or 20%) of all CT images were classified as "not helpful". Fifty-nine examinations (or 65.5%) were "quite helpful" and 13 (or 14.5%) were "extremely helpful." In our retrospective study we demonstrated that a complete evaluation of the pelvic ring is not possible with a series of pelvic overviews alone. Fractures of the sacral body and lateral part of the sacrum are overlooked especially often, but second-degree lesions of sacroiliac joint are also often not seen. PMID- 1519071 TI - [Sonographic diagnosis of the injured acromioclavicular joint. A standardized examination procedure]. AB - The possibility of using ultrasound leads to an improvement and extension of the methods conventionally used for diagnostic examination of the injured acromio clavicular (AC) joint. Periarticular soft tissues can be assessed, as well as the osseous parts making up the joint. Coraco-clavicular ligaments in particular can be visualized well, and the coraco-clavicular distance can be measured precisely. Evaluation of the ultrasound findings makes classification of the grade of severity of injury according to Tossy much easier. We examined 35 injured AC joints of all grades of severity. With two standard planes of examination--a frontal and a sagittal plane--it was possible to obtain information about the grade severity of the injury in every case. Instability of the joint is diagnosed by measuring the coraco-clavicular distance with and without weights pulling on each arm. Standard X-rays of the shoulder remain mandatory to exclude fractures. When ultrasound examination is possible, however, X-ray examination of the shoulder with weights pulling on the arms is unnecessary. PMID- 1519072 TI - [Long-term results of treatment of supra-condylar humerus fractures in children]. AB - From 1982 to 1986, a total of 106 children with supracondylar fractures of the humerus were treated at the trauma surgery clinic in Braunschweig. Undisplaced or slightly displaced fractures were treated with plaster casts. More severely displaced fractures were initially treated by closed reduction under general anesthesia and percutaneous Kirschner wiring. In 72 cases (= 85.7%) a follow-up examination revealed a very good or good result. In 9 cases (= 10.7%) satisfactory results were found and in 3 cases (= 3.6%) unsatisfactory results. The most common complication prejudicing the result was cubitus varus. It was found in 27 cases (= 32.1%), most often with a varus under 10 degrees (19 of the 27 cases). A retrospective study of the 12 cases in which the results were classified as satisfactory or unsatisfactory showed 8 insufficient reductions in fractures with severe instability. PMID- 1519073 TI - [Arthroscopy of the elbow joint. Long-term results, complications and indications]. AB - Based on the results of a retrospective study of 67 patients who had diagnostic and surgical arthroscopy of the elbow from 1977 until 1990, we present the technique, results, complications, and indications for elbow arthroscopy. The average age of the patients was 26 years (range: 11-59). At follow-up, the patients were examined both clinically and radiologically. The results were scored according to Figgie's score, which contains the criteria of pain, function, power, and range of motion. The overall score increased significantly from 61.6 preoperatively to 85.3 postoperatively. The age of the patient did not influence the results. However, patients who were laborers had a poorer outcome than the others. Patients with a preoperative pain of 4 months to 2 years had better results than patients with a preoperative course of more than 2 years. With respect to the criteria (pain, function, power, range of motion), the pain improved significantly, whereas the other parameters showed no significant improvement. Breaking the diagnosis down into three categories (specific diagnosis, degeneration, unclear diagnosis), only patients with a specific and clear preoperative diagnosis showed significant improvement. The high number of neurological complications was especially striking. CLINICAL RELEVANCE: According to our results, patients with loose bodies, early rheumatoid arthritis, and joint infection seem to be good candidates for elbow arthroscopy. However, patients with severe degeneration or patients with unclear preoperative diagnosis will rarely benefit from this procedure. In general, the patients' pain can be treated effectively, but range of motion or power will not increase after elbow arthroscopy.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1519074 TI - [Primary sonographic diagnosis and follow-up of muscular and tendon injuries of the lower extremity]. AB - Ultrasound examination has become an important diagnostic method in muscle and tendon injuries. In addition dynamic ultrasound examination allows evaluation of the course of healing from various aspects. Starting with the sonoanatomy, the pathologic ultrasound patterns typical for injuries to muscle and to Achilles, patellar and quadriceps tendons are demonstrated. As complement to clinical examination, ultrasonography enables appropriate adaptation of the therapy concept to the course of healing. In the hands of experienced operators, ultrasound examination has reached a high level of sensitivity and specificity in these injuries and can justifiably be routinely performed. PMID- 1519076 TI - Community health promotion programs. AB - The theory behind several community-based health promotion/disease prevention programs was reviewed, together with the way theory was put into practice and the outcomes of various interventions. Much has been published on theoretical bases and mechanics of these programs, but evidence linking theory, practice and outcome is limited. Conceptual overlap between theories and models make it difficult to test them with scientific rigour. More basic research is needed to evaluate the relations between the process of change, the target of change and both short- and long-term outcomes. PMID- 1519075 TI - The genetic analysis of human behavior: a new era? AB - Recent developments in DNA-based techniques may revolutionize the study of human behavioral genetics. However, unless these methods are used with great care, many of the same mistakes which have plagued non-molecular genetic analyses of behavior will reoccur. Errors in the application of genetic approaches and in the interpretation of results have been a common feature of published studies in this field. We review studies in human behavioral genetics, focusing on those using identical twins and DNA-based linkage techniques in order to draw attention to recurrent problems in molecular and non-molecular studies. We suggest possible guidelines for future research in the area of the biological basis of human behavior. PMID- 1519077 TI - The negotiation of death: clinical decision making at the end of life. AB - The ability of medical science to prolong biological life through the use of technology raises the question of how far physicians should go in treating the terminally ill patient. In clinical decision making involving the dying patient, physicians, patients and families bring various perceptions and interpretations to the situation. These different realities must be negotiated in order to define the meaning of the situation and the meaning of various medical technologies. The patient's demise becomes a negotiated death, a bargaining over how far medical technology should go in prolonging life or in prolonging death. A case study of the process of ethical decision making in the foregoing of life-supporting therapy in an intensive care setting is presented and analyzed. The decision making process in this case follows a 'cascade' pattern rather than a controlled, reflective model. While ethicists view the withholding and withdrawing of life supporting treatment as morally equivalent, physicians tend to make a distinction based on the perceived locus of moral responsibility for the patient's death. In the author's interpretation the moral responsibility for the patient's death by withdrawing treatment is shared with family members, while the moral responsibility for the patient's death by withholding treatment is displaced to the patient. The author suggests that an illusion of choice in medical decision making, as offered by the physician, begins a negotiation of meanings that allows a sharing of moral responsibility for medical failure and its eventual acceptance by patient, family and physician alike. PMID- 1519078 TI - The psychosocial review of systems. AB - Psychosocial problems have a significant impact on the course and cost of medical illness. However, many of these areas are generally neglected in medical interviews. This manuscript presents a condensed review of the major psychosocial domains, which together constitute what we term a psychosocial review of systems (PROS). Selected references are provided which document the importance of these areas to medical care, and serve as background reading for further inquiry. The psychosocial areas which are covered include: substance use, stress and life events, subjective views of symptoms, daily activity, social support, sexual concerns, finances, psychiatric history and symptoms, cultural issues, and functional status. The Psychosocial Review of Systems (PROS) can serve as a basic overview for the psychosocial aspects of medical education, and also as a content based instrument which has potential for development as an assessment tool to measure physician competence in eliciting relevant psychosocial data. PMID- 1519079 TI - Determinants and dimensions involved in self-evaluation of health. AB - This study explores mechanisms involved in self-evaluation of health by making specifications of linkages among various dimensions of health status, physiological measures, social and behavioral factors or characteristics. The proposed structural equation model is tested by using data from a comprehensive health survey of the population of Finnmark county, Norway (1987-88), including 4549 men and 4360 women aged 30-62. The findings suggest the burden of physical distress and reliance on permanent disablement benefit to play the key role in reducing self-evaluated health. The seemingly strong labelling impact of permanent work disability, contrasted the modest effect of diagnoses of chronic disease. Moreover, the impact of both these key factors and other important determinants is strongly socially patterned. Positive health related life-style appeared to have a positive impact on self-rated health, while preoccupation with health had a negative impact. This finding adds some credibility to the suggestion that the growing occupation and fascination with health have some negative health outcomes. PMID- 1519080 TI - Varied potential risks of HIV infection among prostitutes. AB - To date, most HIV prevention programs targeting North American prostitutes have focused on individual behaviour change, and in particular, the consistent use of condoms between prostitutes and their clients. The organizational and societal level issues which may influence high risk practices within the working and private spheres have received relatively little attention. In addition, most prevention efforts have been limited to targeting the sub-population of street prostitutes. We outline here three different types of prostitutes (street prostitutes, escorts, and prostitutes who work part time in the service sector, i.e. barmaids and erotic massage therapists) known to work in many North American centres. In doing so, we suggest that potential risks of infection vary according to the type of prostitution, and that prevention programs must recognize the diversity in potential risk practices. Differences in the organization of work and working conditions of varied types of prostitutes may, in particular, influence risk practices while working. Some of the individual, organizational and societal level issues which influence risk practices among different types of prostitutes are presented. Much of the research involving HIV and prostitutes has accessed prostitutes at sites where street prostitutes are over-represented. Other studies are based on potentially baised samples as they have recruited prostitutes from medical clinics. Methodologic problems that influence attempts to obtain a representative sample of the prostitute population are discussed. PMID- 1519081 TI - Responses to the institution among elderly patients in hospital long-stay care. AB - The theory of the 'total institution' argues that institutions deliberately create dependency in individuals who would otherwise be self-determining. We examine the significance of this concept for patients in long-stay geriatric wards. All such patients in the South West Thames Region (808) were located and assessed for levels of physical dependency and mental confusion. 87% were profoundly disabled, 53% were severely confused and 23% were seriously ill or unable to communicate. Those capable of responding (291) were interviewed. Three quarters or more were satisfied with 'staff relations', 'autonomy', 'amenities' and 'privacy' and three fifths were satisfied with the 'social environment'. Results suggest that: (a) patients in long-stay geriatric wards who were not severely confused were able to make realistic assessments of their situation and (b) the majority were not passively institutionalized. In terms of institutionalization theory, it is their physical frailty that appears to differentiate this group from other categories of 'inmates'. We conclude that appropriate policy for the long-term ill necessitates consideration of the actual as well as the attributed needs of patients. PMID- 1519082 TI - Physician satisfaction, professional characteristics and behavior formalization in hospitals. AB - In this paper, an analysis is presented of professional and bureaucratic predictors of physician satisfaction. Results from 210 physicians in 17 medical departments of university hospitals support the hypotheses that both professional attitudes and formal structuring of work activities have a positive effect on physician satisfaction. It is shown that behavior formalization, preference for professional autonomy and the time spent on patient care activities within medical departments are positive predictors of satisfaction with work environment, while 'traditional' professional attitudes like craftsmanship and client service have more impact on satisfaction with patient demand. Certification is a strong positive predictor of work load satisfaction. Satisfaction with work environment was the most important factor in explaining other satisfaction dimensions. This finding supports the hypothesized 'buffering' effect of the affective climate or 'feel' of the professional work environment in hospitals. The implication of the findings is, that in the process of bureaucratization of medical practice in hospitals, specific attention should be paid to the maintenance of professional values as guidelines for professional work and to the maintenance of a good affective work environment for professionals in order to prevent dissatisfaction with patient demand and work load. PMID- 1519083 TI - A comparative study of abused and neglected American Indian children in the southwest. AB - Samples of target and control American Indian children in the Southwest United States are compared for child abuse/neglect and family alcohol abuse. Alcohol abuse is present in virtually all families that abuse/neglect children. However, alcohol abuse exists exclusive of the association with child abuse/neglect. The study demonstrates that alcohol abuse is a necessary, but not sufficient, condition for child abuse/neglect. PMID- 1519084 TI - Do Australian researchers accept committee review and conduct ethical research? AB - We sought researchers' views on the ethics of research practice and the Australian system of review of research proposals by research ethics committees (RECs). Researchers were found to be supportive of review of research proposals, even though they thought that the process of review was time consuming and demanding. However, our findings suggest that not all researchers present their research proposals for review by committees, and that some researchers deviate from their approved proposals without seeking approval for those deviations from an REC. Researchers supported monitoring of research by RECs. PMID- 1519085 TI - Joining a healing community for cancer: who and why? AB - This paper provides a description and evaluation of selected aspects of The Wellness California. Based upon participant observation, TWC's philosophy and program are described. The ways in which charismatic leadership is used to create a sense of 'healing charisma' is specified. Interviews were conducted at 3 points over a 10 month period with 65 individuals who initiated contact with TWC. Thirty seven eventually became participants at TWC, while the 28 who did not were used as a comparison group. Participants were healthier, more oriented toward self care and less satisfied with their existing social support networks. The findings indicate the role, and limitations, of healing communities for people with chronic physical illness. PMID- 1519086 TI - Indigenous mortality: placing Australian aboriginal mortality within a broader context. AB - The purpose of this study was to evaluate whether contemporary Australian Aboriginal mortality patterns are different from those exhibited by Canadian Registered Indians, New Zealand Maoris, and American Indians and Alaskan natives. Data on Australian Aborigines were procured from published studies conducted in New South Wales, the Northern Territory, Queensland, and Western Australia; while data on Canadian Registered Indians, New Zealand Maoris, and American Indians and Alaskan natives were obtained respectively from unpublished tables produced by Health and Welfare Canada, the National Health Statistics Centre, and the Indian Health Service. Mortality patterns were compared by evaluating differences in life expectancy and in age- and cause-specific patterns of death. This analysis demonstrates that although Australian Aborigines, Canadian Registered Indians, New Zealand Maoris, and American Indians and Alaskan natives have similar patterns of high adult mortality, Australian Aborigines are generally characterized by lower life expectancies at birth and higher age- and cause specific death rates. Overall, these findings suggest that the mortality patterns of Australian Aborigines are strikingly different from those exhibited by the other three indigenous populations and that existing information on risk, psychosocial, and genetic factors does not really explain why Australian Aborigines as compared to these other indigenous groups have such high rates of death and low life expectancy. PMID- 1519087 TI - Verbal exchanges in medical interviews: concepts and measurement. AB - The verbal exchange theory of medical interviews (consultations) proposes that patients and clinicians employ a joint repertoire of exchanges to accomplish their goals in the encounter. The skeleton of each exchange is a set of speech acts that tend to be used together in interviews, for example, (a) clinician questions and patient yes/no answers, or (b) clinician directives and patient agreements to comply. We describe seven principal exchanges, each of which has been identified empirically in multiple studies of interviews: Exposition, Closed Question, Checking, Direction, Inquiry, Explanation, and Instruction/Contracts. PMID- 1519088 TI - Assessment of the outcomes of health intervention. AB - In this article we discuss basic assumptions of health interventions with regard to their underlying concepts and selected strategies. Particularly, the lifestyle model of health promotion is presented and its consequences for health promotion and health interventions are discussed. Reference is made to two fields of interventions: prevention of cardiovascular diseases and worksite health promotion. It is concluded that health interventions have to clarify their concepts and strategies in detail before an evaluation of their outcomes can be carried out reasonably. PMID- 1519089 TI - Assessment of outcomes of health intervention. AB - This paper proposes that the most comprehensive current approach to the assessment of health interventions is exemplified in the expanding field of research into health-related quality of life. The paper initiates discussion of 11 conceptual and methodological issues which should be dealt with explicitly rather than by default in any such research study. Decisions about these 11 issues will shape the future directions of the field of health outcomes research. Health policy decisions will increasingly be based on outcome studies of health related quality of life. PMID- 1519090 TI - Changes in disease patterns and related social trends. AB - Both the material and non-material aspects of social life are viewed as determinants of major transformations in the patterns of fatal disease and injury. A 'worst case' scenario for the burden of fatal disease is taken as a poor agrarian society precariously dependent on starchy staples and a narrow range of other foods. In such a society life expectancy may be as low as 20. However in many 'pre-modern' societies the regime of roughly matching fertility and mortality levels was set at a 'submaximal' level, with completed fertility rates moderated by marriage conventions. The relative importance of the factors contributing to the historical decline in fatal infection continues to be debated. Evidence on the central role of maternal literacy in the recent decline in Third World mortality suggests the importance of changes in the body of civil society as well as the activities of professionals and public agencies. The decline in fatal infections has been offset to varying extents by an increase in non-communicable disease (NCD): the Mediterranean and East Asia having smaller epidemics of NCDs and Eastern Europe having sustained rises of NCDs. Most industrialised countries have experienced declines in overall NCD mortality in the last 2 decades. Both the fall in fatal infection and the rise and early fall of NCDs can usefully be viewed against the baseline of hunter gatherer cultures. When this is done, the relationship between economic development and disease is seen to be complex. Much 'progress' has been achieved by countering (and then doing better than countering) the adverse effects of earlier developments. Although most members of the generation now alive have experienced marked health benefits from economic and technical advance, it is unclear whether these gains can be both sustained and generalised. It is possible that adverse lagged effects of current industrial (and military) activities will disrupt the habitat of future generations of our species through processes such as stratospheric ozone depletion, global warming and others as yet unpredicted. Modern hygienists have dealt successively with influences on survival mainly operating in early life (infection) and influences operating across the lifespan (determinants of chronic disease). They have now to deal with even greater separations in time and space between potential health determinants and their ultimate effects. To a high level of scientific uncertainty is added the ethical problem of equity between generations. PMID- 1519091 TI - Changes in disease patterns and related social trends. AB - Social environment is a major determinant of health and disease patterns in any community. The 19th century revolution in public health had as its cornerstone the improvement of social and physical environment. The favorable social development has since that time significantly contributed to the decrease of traditional health hazards in developed countries. New public health problems, chronic diseases have emerged in these countries. In some of these nations a new trend has started that may be called the second revolution in public health, i.e. the reduction of chronic diseases. However, the major part of the world's population still suffers from the traditional illnesses that should and could have been set aside by the 19th century revolution. Obviously, the social environment has not been altered sufficiently in these areas to have the desired impact on the health status. The observations from the Eastern European countries stress the need for a purposeful avoidance of deprivation in the social and physical environment as prerequisites for the prevention and control of diseases. Generally, low socio-economic status has been found to relate to an increased risk in many diseases. Usually there is a definite time lag between changes in social trends and disease patterns which causes difficulties for research in this area. The same fact generates problems for the planning and implementation of interventions to prevent the socially affected diseases. Changes in disease patterns are not only determined by altered social trends, but disease patterns can also influence social tendencies in several ways. Studying the interaction of social and health trends quantitatively and experimentally has yielded results which are hard to interpret. Therefore, observational and 'soft' methods are employed here to describe the relationship of social and health trends more aptly. PMID- 1519092 TI - On the epistemology of risk: language, logic and social science. AB - 'Risk' is a widely used concept in literatures related to health, health care and medicine. In recent decades, three bodies of literature have emerged in which 'risk' is the primary focus of concern: Health Risk Appraisal, the Risk Approach and Risk Analysis/Assessment/Management. These literatures overlook important concepts and theoretical developments in contemporary social science. They also lack conceptual coherence. Reduction of incoherence will require re-examination of the epistemology of risk in relation to both its language and its logic in light of developments in social science. PMID- 1519093 TI - Cultural influences in community participation in health. AB - The adoption of Primary Health Care in developing countries brought a new interest in the influence of cultural factors in community health programs. This paper traces the changes in the way that the role of culture has been analyzed in relation to community health issues and in particular with respect to 'community participation'. A look at recent perspectives shows that the fate of community health programs has come to be seen as relying more on structural factors in health care systems than on cultural factors within local communities. There has also been an increasing emphasis on political factors or power relationships within and between health agencies, governments, and various levels of national health care systems. These perspectives raise new questions for community health programs and the strategy of community participation. PMID- 1519095 TI - Dying with dignity. AB - Death is a theme of central importance in all cultures, but the manner in which it is interpreted varies from society to society. Even so, traditional cultures, including Christian, Hindu and Jain religious traditions, exhibited a positive attitude to death and did not look upon it in a dualistic framework of good vs bad, or desirable vs undesirable. Nor was pessimism the dominant mood in their thinking about death itself. A fundamental paradigm shift occurred in the West in the eighteenth century when death was desacralized and transformed into a secular event amenable to human manipulation. From those early beginnings, dying and death have been thoroughly medicalized and brought under the purview of high technology in the twentieth century. Once death is seen as a problem for professional management, the hospital displaces the home, and specialists with different kinds and degrees of expertise take over from the family. Everyday speech and the religious idiom yield place to medical jargon. The subject (an ageing, sick or dying person) becomes the object of this make-believe yet real world. As the object of others' professional control, he or she loses the freedom of self-assessment, expression and choice. Or, he or she may be expected to choose when no longer able to do so. Thus, not only freedom but dignity also is lost, and lawyers join doctors in crisis manipulation and perpetuation. Although the modern medical culture has originated in the West, it has gradually spread to all parts of the world, subjugating other kinds of medical knowledge and other attitudes to dying and death.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1519094 TI - Cultural and structural influences in the creation of and participation in community health programmes. AB - Community participation in health care programmes is considered axiomatic in health development. Cultural and structural influences are discussed in relation to community participation with the intention of highlighting some critical issues affecting its generation and sustainability. These influences include structurally defined perspectives and perceptions of community participation, limitations of the necessary supportive systems, the structural and cultural factors of marginalization, community stratification and organization, mobilization, and the political context. It is concluded that given these factors against a situation of a financial and economic crisis, of economic restructuring and the values of competition and individualization, community participation will be increasingly difficult to generate and sustain. PMID- 1519096 TI - To die with dignity. AB - This paper examines the conundrum facing an individual with a terminal disease who wishes to end his or her life in a manner that maintains a minimum of dignity. The State's interest versus the individual's right to live or die is examined in its various aspects. The interference by the State supplanting the Church as the authority that interprets the boundaries between life and death, with the individual losing his voice as well as his body to the impersonality of maintaining a life not worth living, is studied, as well as the implicit dangers when the freedom to decide when and who should die is measured against the present international economic situation. The need to listen to the language of the dying as well as to their need for a 'closure' is approached with a view to future study. PMID- 1519097 TI - Birth Order and health: major issues. AB - Birth Order has been described as a variable with a complex relationship to child and adult outcomes. A review of the medical literature over the past 5 years identified 20 studies that investigated the relationship between Birth Order and a health outcome. Only one of the studies established a relationship between Birth Order and a health outcome: third and fourth-born children have a higher incidence of accidents that result in hospitalization. The other demonstrated relationships are each explained by intervening variables or methodological limitations. Although Birth Order is not a strongly independent explanatory factor in understanding health outcomes, it is an important marker variable. Statistically significant relationships between Birth Order and health outcomes yield insights into the ways a family influences an individual's health. PMID- 1519098 TI - The effects of family position and status on health. AB - In the last couple of decades there has been a considerable amount of research, mainly in the U.S.A., on the effects of family position on health. This paper reviews material on (a) the impact of family of origin on health and (b) adult family position and health. Parental divorce is shown to be related to a range of adverse outcomes in childhood, adolescence and adulthood. Marriage and parenthood are associated with longevity and good mental and physical health. This paper argues for more research in other cultural settings, for panel studies, for more direct measures of the roles and processes often inferred from structural variables, and for the use of measures of physical development and functioning. PMID- 1519099 TI - Equity and efficiency in health care. AB - Adam Smith's belief that markets will make society more equitable and efficient is examined in the case of reforms to make health care more competitive. Eight ways in which health care does not often satisfy the requirements for competitive markets, and nine ways in which providers can manipulate markets are identified. The concept of 'embedded inefficiencies' is introduced to explain why competition may not increase efficiency. PMID- 1519100 TI - Substance abuse and control in the United States: ethical and legal issues. AB - In 1986, the United States began to wage its most recent War on Drugs. This has involved establishing various policies and making investments to implement these policies and approaches. In general, the U.S. has taken a tough-guy stand to drug abuse and control that emphasizes punishment, restriction, and 'social warfare', as opposed to a public health oriented position. Current policy reflects a 'quick fix' solution to a complex problem, which may partially explain its failure and why we appear to be losing the War on Drugs. In this review I summarize the current debates and controversies surrounding drug abuse in the U.S. regarding the extent of the drug problem, the need for drug control, prevention efforts, legalization controversy, workplace strategies, treatment dilemmas, and maternal drug abuse. I argue that a radically different approach must be taken that is grounded in public health methods and an appreciation of the larger social context in which drug abuse occurs. We must look for a long-term solution to this complex problem that is integrated into society, and which is certainly resistant to the current quick fix approaches. PMID- 1519101 TI - Ethical and legal issues in the control of drug abuse and drug trafficking: the Nigerian case. AB - This paper presents a general review of drug law and policy in Nigeria beginning with the international attempts to control the traffic in liquor during the pre colonial and colonial periods. The paper assesses the impact of penal policy on trafficking and use of illicit drugs at different stages in the transformation of Nigeria from a colonial outpost to an independent nation. One persistent feature of drug control mechanisms in Nigeria has been the emphasis on the reduction of supply with the imposition of harsh though inconsistent punishment including, at one time, the death penalty for trafficking. Consequently, initiatives aimed at demand reduction through education, treatment and rehabilitation have been neglected. One reason for this is that, to a great extent, drug control strategy in modern Nigeria has been a response to international demands; another is that they were formulated under military regimes with an overriding concern for law and order. Other features of the Nigerian drug problem are presented and the need for the reform of current laws is stressed. It is argued that an enduring solution lies in the implementation of a comprehensive but clearly defined policy aimed both at the control of supply and reduction of demand. While the state has the duty and the right to protect its citizens from drug-related harm, it is an ethical imperative to institute control measures which do no harm to the citizens they are meant to protect. PMID- 1519102 TI - Ethical and legal implications of the new genetics: issues for discussion. AB - The so-called 'new genetics,' a phrase sometimes associated with The Human Genome Initiative, poses no really new ethical problems, but exacerbates old ones. The issues of most concern to geneticists and their patients are summarized under the eleven headings below. These issues emerged from a 19-nation study of ethics and genetics in 1985-86 and from preliminary work on a forthcoming 36-nation study by the same authors. PMID- 1519103 TI - Health and social problems of refugees. AB - Today over 15 million refugees are scattered around the world, most of them in poor Third World countries [New Sci., pp. 14-15, September 1991]. But whether they seek 'safe havens' in rich or poor countries they continue to suffer from the malaise of being uprooted, struggling to survive in new and alien environments. Their health and social problems extend beyond the obvious emergency short-term phase. It is now clear that the number of refugees has increased beyond expectations and most have stayed long enough to expect final resettlement in their countries of asylum, a process which requires wider, more comprehensive and long-term management and rehabilitation interventions. This paper will attempt to highlight issues of health and social problems in their wider context, surveying comprehensive and integrated approaches in assessing the needs of refugees, whether they are in developing or industrialised countries, with emphasis on the latter and, when appropriate, using the United Kingdom experience as an example. PMID- 1519104 TI - New paradigms for refugee health problems. AB - Two paradigms that have shaped our understanding of refugee health are identified: the objectification of refugees as a political class of excess people, and the reduction of refugee health to disease or pathology. Alternative paradigms are recommended: one to take the polyvocality of refugees into account, and one to construe refugees as prototypes of resilience despite major losses and stressors. The article is organized into three sections, mirroring the life history of refugees from internal displacement in the country of origin to asylum in a second (usually neighboring) country, and for some, to permanent resettlement in a third country. In each of the three sections, the primary topics that are treated in the literature are identified, and key problems identified for discussion. PMID- 1519105 TI - Health care consequences of the European economic community in 1993 and beyond. AB - Generally, health services are not covered by the treaties of the European Community. However, to an increasing extent the EC has and will have an influence on national health systems. In particular the effects of regulations made for other sectors have repercussions for health. For example the free movement of labour and the harmonization initiatives have direct effects on the educational curricula for health professions and may, in time increase professional migration within the community. Within the EC research programmes health related topics have been included to an increasing extent. This goes in particular for medical informatics, standardization, quality assurance systems and pharmaceuticals. Indirect effects of the single market will probably appear within the area of insurance, public purchasing and building and other types of construction works. Other areas that probably will be influenced are record security and occupational health benefits. PMID- 1519106 TI - Impediments to basing government health policies on science in the United States. AB - In the U.S., there is no consistent relationship between what health scientists find and public policy. Some scientific findings are heralded and quickly incorporated into individual and political action. Other findings are ignored, and others are contradicted by policy. This paper explains this inconsistency in terms of individual reaction to hazards, media coverage of hazards, and different ability of individuals to respond to health information; political leaders' preference for high-technology science, distortion and opposition by commercial interests, bureaucratic maneuvering for power and resources; and uncertainty and asymmetry of some scientific findings. PMID- 1519107 TI - Realities of Health For All by the year 2000. AB - The European Region of the World Health Organisation (WHO) took the global lead on Health For All when the Regional Committee in 1980 approved a European Health For All Strategy. This was an important breakthrough for WHO as it was the first time Member States in a Region endorsed a common health policy and agreed to be monitored on their progress towards attainment of the strategy. The paper reviews the progress of Member States to date towards the Regional Health For All goal. Progress is discussed within the context of the six fundamental principles which underpin the Health For All concept, vis: equity; health promotion; community involvement; multisectoral participation; primary (local) health care; and, international cooperation. The paper argues that the commitment of Member States to the Health For All Strategy has been patchy with only moderate success towards meeting the 38 Regional Targets. Poor progress is attributed to changing national and international political and economic circumstances and limited resources but perhaps most importantly to a lack of political will to take the strategy seriously. PMID- 1519109 TI - Doctors as managers: poachers turned gamekeepers? AB - Doctors in health care systems of different types are coming under increasing pressure to take on active roles in management. Mounting concern among governments over the escalating costs of health care, coupled with a desire to improve the quality of care and render services more responsive to user preferences has resulted in management being viewed as offering an effective means of tackling these issues. Until recently, the favoured strategy was to strengthen management in order to curb doctors' discretionary decision-making. There is now a shift towards creating managers out of doctors with all that this implies for the future shape of health services. There are also issues about the training and development required for a management role, the stratification of roles within the medical profession, and the future status of lay, or non-medical managers. The paper reviews the debate about doctors and managers and their distinctive value bases. It suggests that doctors can be involved in management as managers at two levels--meso and micro--and considers the issues raised at each level. The paper presents an analysis of the wider context in which the debate about doctors as managers is taking place. The main thesis put forward is that far from managers incorporating doctors, the end result may prove to be the other way round with 'provider capture' of the management agenda in health services a distinct possibility. In contrast to managers, doctors retain enormous public respect and support. As long as it is so doctors will remain powerful stakeholders in defining and controlling the shape and range of health services available. Their active involvement in management could lead to a strengthening of their position. It is argued that, paradoxically, this could make it more difficult for governments to challenge doctors' work practices. Medicine's traditional preoccupations and its resilience to change are likely to remain as strong as ever thereby disappointing advocates of a health and social care system located in a broader policy framework which emphasises health gain and a holistic approach to health. PMID- 1519108 TI - The role of doctors as health care managers: an international perspective. AB - The participation of physicians in health care management has followed different paths in developed and developing countries. However, we can say that in most of the countries the physicians have had cyclical patterns of participation and withdrawal from health care management. It is readily apparent that these patterns are different in each country. We propose to take into account three different levels of analysis in which different factors interact to define the country specific pattern of physician involvement in health care management, as well as to assess the international convergence and divergence paths on physician participation. We present here a conceptual framework that could facilitate the analysis of this theme under a comparative perspective. We start by discussing a conceptual framework of the determinants of physician participation in health care management. Then, we assess the current trends and perspectives in both developed and Latin American countries of physician participation in health care management. PMID- 1519111 TI - Challenges to understanding spatial patterns of disease: philosophical alternatives to logical positivism. AB - Most studies of disease distribution, in medical geography and other related disciplines, have been empirical in nature and rooted in the assumptions of logical positivism. However, some of the more newly articulated philosophies of the social sciences, and of social theory, have much to add in the understanding of the processes and mechanisms underlying disease distribution. This paper represents a plea for creative synthesis between logical positivism and realism or structuration, and uses specific examples to suggest how disease distribution, as a surface phenomenon, can be explained using deeper analysis. PMID- 1519110 TI - High cost technology in health care: a benefit or a burden? AB - The influence of high cost technology goes beyond its consequences for the selected patient groups that benefit from its application. Past and future technological developments have a variety of social, economic and ethical implications which have to be taken into account when balancing its costs and benefits to society. Departing from an economic perspective we describe a number of mechanisms underlying the emergence of high cost technology which help us to understand some of the characteristics of high cost technology, such as its focus on quality enhancement rather than on economy. To assess the actual performance of high cost technology in terms of efficiency and equity is difficult as there may be debate about the perspective guiding such assessment and as there still is scarce information on high cost technology in terms of these economic indicators. The increasing technological opportunities have triggered a wider debate on the desired evolution of our health care systems. In some countries there is a tendency to diminish government involvement in health care and emphasize private (for profit) enterprise as a reaction to not being able to finance all new high cost technology. The risks of such strategies are discussed briefly. We conclude that the main actors in health care should adjust their behaviour in order to accomplish the introduction of more cost-effective technologies and to achieve a more socially efficient distribution of their benefits. PMID- 1519112 TI - Threats to the world eco-system: a role for the social scientists. AB - This paper seeks to identify some of the major threats to our fragile eco-system through human actions. We have sought to highlight that since these threats to our composite ecological heritage are global in nature, our responses shall have to be at the global level. We have tried to analyse a role the social scientists can exercise in response to these threats. We have merely shown possible responses within their professional disciplines. Can they play an activist's role? The paper does not prescribe any push-button role while emphasizing role of social scientists in environmental education. Every discipline among the social sciences will need to carve out its own role keeping in view local conditions. The current stocktaking of the situation under the UNCED process may require the international community to review existing institutional structures in the field or create new ones. PMID- 1519113 TI - Existential ecology: the human/natural world. AB - Medicine and ecology share the concern for reconciling human aims and natural processes. That reconciliation is attempted through analogous approaches in the two fields. A dialectical model, described here, provides conceptual organization of those approaches into a coherent progression of paradigms, both existential and theoretical: (1) vulnerability, the immediacy of human exposure to nature's power and the futility of human ascendancy; (2) disengagement, the rational and the romantic objectification of nature; (3) dissection, the scientific and cultural reduction of nature to specimens; (4) holism, the conceptualization of the ecosystem; (5) inherence, the human involvement with nature as home, entailing a local rather than colonial ethic and epistemology. Culmination of the dialectic in ecology, as in medicine, is reconcilation with the otherness of nature, recovering both environment and embodiment as forms of human existence. PMID- 1519114 TI - The use and value of qualitative methods in health research in developing countries. AB - Qualitative and quantitative research methods for public health were integrated in the past. Work at the Polela Health Center and the Institute of Family and Community Health (South Africa) in the 1940's epitomized how true integration was possible. Since the 1950's the growth of disciplines and boundaries between them; the growing emphasis by funding agencies on quantitative research that yields results rapidly at low cost and the dominance of the medical profession in public health together resulted in a separation of approaches. Recently, recognition of the need for integrated approaches has reemerged but the capacity to conduct appropriate research in developing countries is weak and they have relied on importing both researchers and their methods. Examples are given (mainly using focus group methods) of how innovative integrated approaches in developing countries have been used to implement community diagnoses, understand factors affecting health service utilization and identify factors amenable to intervention. It is concluded that while qualitative methods are needed (and used) in developing countries, their use will only increase if appropriate training initiatives in developing countries are undertaken. PMID- 1519115 TI - Women's access to health care in developing countries. AB - Women in developing countries are frequently confronted with a myriad of socio cultural factors which negatively impinge upon physical well-being and accessibility to appropriate health care services. Institutional, economic, and educational barriers effect and lowers their standard of living when compared to their male counterparts. Women must become agents of change to improve their situation. Factors such as access to income, legal rights, social status, and education may prove far more important in determining women's access to health care than technology distribution and governmental strategies. PMID- 1519116 TI - [Local recurrence in head and neck tumors: computed tomography]. PMID- 1519117 TI - [CT-guided lumbar sympathicolysis. Technique and results]. PMID- 1519118 TI - [Magnetic resonance tomography of the bone marrow in malignant hematologic system diseases. A review with special reference to magnetic resonance tomographic techniques]. PMID- 1519119 TI - [The significance of the costs of contrast media for society]. PMID- 1519120 TI - Neuro-endocrine tumours--their origin and classification. AB - The neuro-endocrine cell is an integral component of many organ systems, and it is therefore not unexpected that this cell is identified in a variety of tumours. The embryology of this cell is uncertain and the recent literature indicates the presence of more than one type of neuro-endocrine cell. The classification of neuroendocrine tumours is addressed, a working classification is proposed and attempts made to clarify the concept of neuro-endocrine neoplasia. PMID- 1519121 TI - Occlusive versus semi-open dressings in the management of skin graft donor sites. AB - In a prospective, randomised study we compared the efficacy of a new occlusive dressing (Granuflex-E) with a semi-open dressing (tulle gras) in the management of skin-graft donor sites. The study examined 10 patients with burns, each with two donor sites. Each patient acted as his or her own control. The donor sites were mirror images of each other, the anterior surface of the thighs. One donor site was dressed with Granuflex-E and the other with tulle gras. The sites dressed with the occlusive dressing healed significantly faster and were more comfortable than the sites with the semi-open dressing. PMID- 1519122 TI - The effect of hypovolaemia on healing of the right and the left colon. An experimental study. AB - An experimental study was carried out to investigate the effect of a period of hypovolaemia prior to surgery on healing of the right and left colon of the baboon. Colonic healing was assessed in three ways: in terms of (i) anastomotic leakage, (ii) hydroxyproline concentrations and (iii) breaking strength. The results suggest that hypovolaemia before surgery affects the right and left colon similarly. PMID- 1519123 TI - Post-traumatic spontaneous gangrene of the right colon. A case report. PMID- 1519124 TI - Penetrating cardiac injury--to close the pericardium or not? A case report. AB - Many trauma surgeons who treat penetrating cardiac injuries do not routinely suture the pericardium closed after repairing the heart. The patient reported here died from exsanguination during attempts to mobilise the heart which had adhered to the sternum. With the increasing demand for coronary artery surgery and the high incidence of carcinoma of the oesophagus in South Africa, both of which require access to the mediastinum, we recommend that in the trauma setting, the pericardium be closed to facilitate future surgery if required. PMID- 1519125 TI - Linear stapling device in partial resection of abdominal parenchymatous organs. AB - The use of the linear stapling device (LSD) is well-established in hollow-organ gastro-intestinal surgery. Its use in operations performed on parenchymatous viscera is less common. We present our experiences with the LSD in partial resection of the spleen (2 cases), pancreas (5 cases), liver (2 cases) and kidney (2 cases). To the best of our knowledge the use of the LSD for partial nephrectomy and resectional debridement of the liver has not been previously described. We suggest that LSDs are useful aids in the resection of parenchymatous organs, and allow rapid resection if applied to healthy tissues and in regions with an intact capsule. PMID- 1519126 TI - Functional improvement following thrombo-endarterectomy for chronic pulmonary thrombo-embolic disease. A case report. AB - Pulmonary thrombo-endarterectomy for chronic pulmonary thrombo-embolic disease is an underutilised and potentially lifesaving therapeutic manoeuvre. This case study describes the functional improvement that can be attained by such a procedure. PMID- 1519127 TI - Myocardial stunning and hibernation. PMID- 1519128 TI - Anabolic steroids. PMID- 1519129 TI - Blood transfusion--transmission of bacteria and some viruses. PMID- 1519130 TI - Superantigens--progress in understanding microbial pathogenesis. PMID- 1519131 TI - Transplantation in developing countries. PMID- 1519132 TI - Drugs in sport--results of the past 6 years of dope testing in South Africa. AB - Screening procedures were performed on 2,066 urine specimens collected from competitors in 17 different sports during the period 1986-1991. Samples were tested by gas chromatography and gas chromatography/mass spectrometry for the presence of stimulants, narcotics and anabolic steroids. Drugs classified as forbidden substances by the International Olympic Committee were detected in 113 (5.5%) of the samples. Nineteen-nortestosterone and fencamfamine were the anabolic steroid and stimulant most frequently detected. The ephedrines as a group accounted for 35 (31.0%) of the positive samples. This high incidence of the use of banned substances indicates that the dope testing programme to curb use of banned substances by competitors in sport should continue and be expanded to other sports. PMID- 1519133 TI - Androgenic anabolic steroid use in matric pupils. A survey of prevalence of use in the western Cape. AB - A survey was undertaken to determine the prevalence of use of androgenic anabolic steroids (AAS) by matric pupils in the western Cape. A cluster sample, stratified by language and a subjective assessment of sporting status, of 13 schools in the area was selected, and 1,361 pupils completed a questionnaire containing questions about sports participation and the use of AAS. The prevalence of use of AAS in the sample was 5.9/1,000 and prevalences in subgroups were 11.7/1,000 for males, 12.5/1,000 for male sports participants and 25.4/1,000 for Afrikaans speaking male sports participants. A significant amount of under-reporting (AAS users denying their status as such) occurred. General knowledge about AAS was poor, particularly among females and non-sports participants. AAS users experienced more pressure to perform well at sport than did non-users; the drugs were obtained mostly from peers and no user indicated that they were legally obtained. Because there is much evidence regarding the detrimental effects of AAS on health, it is clear that a strategy must be adopted to decrease the prevalence of their use in the schoolgoing population. PMID- 1519134 TI - Detection of Chlamydia pneumoniae in coronary arterial fatty streaks and atheromatous plaques. AB - There is serological evidence that a recently described new strain of Chlamydia, namely Chlamydia pneumoniae TWAR, is associated with coronary artery disease. This study describes the detection of TWAR organisms in the coronary arterial fatty streaks and atheromatous plaques in 7 autopsy cases. TWAR-like organisms were observed ultrastructurally in the lipid-rich core area of fibrolipid plaques and in intimal smooth-muscle cells. In 5 cases, immunoperoxidase staining showed positive reactions to Chlamydia genus- and C. pneumoniae species-specific monoclonal antibodies. PMID- 1519135 TI - South African obstetricians' views on caesarean section. AB - The widespread increase in the rate of caesarean sections performed in the Western world has become a cause for concern. In this country, two systems of health care exist, one provided by the State and the other based on private practice. A high incidence of caesarean sections has been reported, especially among private practitioners. This study investigated doctors' perceptions of caesarean section practices and explored the availability of facilities which could help to reduce the high caesarean section rate. Questionnaires were mailed to all registered obstetricians. Of these 45.2% (233) responded. Findings indicate that private obstetricians are more likely to perform caesarean sections even though they do have good facilities available to monitor or assess difficult deliveries. Other factors influencing their practice are also explored. PMID- 1519136 TI - Tracheobronchial foreign bodies. Experience at Red Cross Children's Hospital, 1985-1990. AB - Ninety-six children with suspected tracheobronchial foreign bodies were referred to the Department of Cardiothoracic Surgery at Red Cross War Memorial Children's Hospital, Cape Town, between February 1985 and February 1990. Foreign bodies were removed by rigid bronchoscopy from 63 patients, 79% of whom were under 5 years of age. The majority of patients (59%) presented more than 24 hours after aspiration of the foreign body, and this delay in definitive management was associated with an increased incidence of complications (P = 0.01). Complications occurred in 28 patients, and there was one fatality at bronchoscopy due to overwhelming aspiration of an unanticipated release of pus, following the removal of a chronically impacted foreign body. The complete classic diagnostic triad (sudden onset of coughing, wheezing and decreased air entry) was seldom present, and we recommend diagnostic bronchoscopy in children presenting with either a history of sudden choking or a witnessed aspiration of a foreign body, an unexplained acute wheeze or cough or a chronic pulmonary infection. This report also highlights the continued need for increased awareness on the part of both parents and medical practitioners of the need for early referral if a foreign body is suspected. Furthermore, public education is needed as regards the dangers of allowing young children to eat peanuts. Peanuts were the commonest foreign bodies removed. PMID- 1519137 TI - Infantile hypertrophic pyloric stenosis in a Third-World environment. AB - Sixty-two consecutive patients with hypertrophic pyloric stenosis, presenting over a 6-year period, are reported. The sequelae of late presentation and diagnostic delay are outlined. Clinical diagnosis may be difficult. Barium meal examination has proved a more useful single investigation than ultrasonography, although these methods of investigation are complementary. Management difficulties include severe biochemical derangement, correction of which delays surgery. In black communities pyloric stenosis remains a rare condition and heightened clinical awareness remains the most important means of achieving earlier diagnosis. PMID- 1519138 TI - The proposed death certificate for South Africa. Part I. Death certificate description. AB - An altered 'Cause of Death' certificate is proposed. The major changes involve the use of the international format for certification of death and provision for collection of extra data, i.e. estimated age at death, sex, population group and, where relevant, the mass of an infant at birth. The new format will facilitate improved data collection and the certificate will stand international comparison. PMID- 1519139 TI - The proposed death certificate for South Africa. Part II. Feasibility study. AB - The proposed new death certificate was tested in urban and rural hospitals and among general practitioners. Of the 471 death certificates returned, 70% were correctly completed. The underlying cause of death was identifiable in 86.6% of cases. The accuracy of cause of death statements was analysed in greater detail. Some items on the proposed form were not clear and needed improvement, i.e. instructions to mark an applicable answer and refer to instructions on the reverse page. The participants completed a questionnaire to assess and comment on the new form. A refined version thereof was prepared as a result of this study. PMID- 1519140 TI - Peri-operative mortality in the anaesthetic service at Tygerberg Hospital. AB - This study reports on the process of peer review of peri-operative mortality at Tygerberg Hospital. The peri-operative mortality rate for the past 3.5 years was 11.9/10,000. The departmental evaluation committee thought that 3.4/10,000 of these deaths were anaesthetic-related. In 2.3/10,000, the anaesthetic contributed to the death of the patient and in 10 cases (total case load = 94,945; i.e. 1.1/10,000) anaesthesia was responsible for the death of the patient. The majority of the peri-operative deaths (8.5/10,000) were caused by a combination of trauma and haemorrhagic shock. PMID- 1519141 TI - Comparative assessment of phase contrast microscopy and Coulter counter measurements in localising the site of haematuria. AB - Haematuria is a common diagnostic problem in clinical practice and is seen in a large number of renal, urological and systemic disorders. The routine use of dipstick methods has increased the frequency of detection of microscopic haematuria. It is desirable to develop a simple, non-invasive, easily reproducible, quantitative technique that would help to determine the site of bleeding and thereby direct the patient either to the nephrologist or to the urologist. This study compares the accuracy of phase contrast microscopy with Coulter counter measurement of red cell distribution volumes as a means of distinguishing glomerular haematuria from non-glomerular haematuria. Of 20 patients with biopsy-proven glomerulonephritis, 13 (65%) were correctly identified by phase contrast microscopy and 19 (95%) by the Coulter counter method. In 18 patients with pathological conditions affecting the lower urinary tract phase contrast microscopy was correct in 6 (33%) and Coulter counter measurement in 17 (94%). Coulter counter measurement is the simpler and more accurate method of screening for the source of haematuria, but is inaccurate when the red cell count in the urine is less than 0.02 x 10(12). PMID- 1519142 TI - No osteoporosis detected by quantitative computed tomography in postmenopausal black females. AB - Problems associated with postmenopausal osteoporosis are believed to be almost non-existent in black South African females, but published data on their bone mineral density are lacking. In this study, vertebral quantitative computed tomography was performed on 30 postmenopausal black women with no complaints other than those attributable to oestrogen deficiency. The mineral bone density was plotted against those 'normals' of similar age provided by the Somaton DR H (Siemens) data base. In all instances the vertebral bone mineral density obtained was higher in the study group. PMID- 1519143 TI - The pattern of poisoning from traditional medicines in urban Zimbabwe. AB - A 10-year (1980-1989 inclusive) retrospective study was carried out at Zimbabwe's six main urban hospitals to evaluate the epidemiology of poisoning caused by traditional medicines. A total of 1456 cases were recorded, and this represented 23% (the biggest single group) of all poisoning cases. Sixty-seven per cent (982) of the patients were male and 33% (474) were female. The majority of patients (53%; 776) were under 5 years of age; 18% (264) were 21-30 years old; the 31-40 year age group accounted for 9.1% (132) of patients, and the 11-20-year age group for 6.7% (97). A mere 1.5% (22) of patients were over 60. Sixty-one per cent (892) of all cases were of poisoning associated with medication (treatment) and 8% (113) were accidental poisonings, while suicides and parasuicides accounted for 0.2% (3) and 2% (30) respectively. The mortality rate was 6% (2% of deaths were accidental and/or treatment-related). The main reasons for seeking treatment with traditional medicines were for depressed fontanelles and fever in children and diarrhoea and abdominal pain in adults. Treatment consisted mainly of supportive therapy and involved the induction of vomiting with ipecacuanha in children. This study indicates that the use of traditional medicines is common in Zimbabwe. PMID- 1519144 TI - Drug survey among first-team schoolboy rugby players. PMID- 1519145 TI - Drugs in sport. PMID- 1519146 TI - Population dynamics and the AIDS epidemic. PMID- 1519147 TI - Why AIDS is not a notifiable disease. PMID- 1519148 TI - Acute haemorrhagic conjunctivitis outbreak. PMID- 1519149 TI - Cost of breast preservation surgery for cancer in the RSA. PMID- 1519150 TI - Thoracoscopic wedge resection. AB - Thoracoscopic surgery is decidedly expanded by the ability to perform pulmonary wedge resections of the lung by using the Endo-GIA-stapler. In addition to thoracoscopic biopsies, since July 1991 we have carried out wedge resections in 12 patients suffering from spontaneous pneumothorax (nine) or peripheral bronchial carcinoma (three). Postoperatively one air fistula persisted over 9 days. The chest tube was removed within 48 h in all other patients. There was no other major complication. The postoperative hospitalization period lasted 4.6 days (1-9 days). Operating time was 44 min (30-70 min). The benefit for the patient consists in the little-impaired breathing mechanics, the short hospital stay, and the favorable cosmetic result. PMID- 1519151 TI - Chest drain penetration into the transposed stomach after Ivor-Lewis esophagectomy: diagnosis by early postoperative endoscopy. AB - A case of chest drain tip penetration into the gastric lumen 3 days after esophagectomy is reported. Early diagnosis by endoscopy in the immediate postoperative period facilitated our management. PMID- 1519152 TI - Minitracheotomy: a new interventional technique for treatment of sputum retention. AB - Sputum retention causing pulmonary atelectasis, secondary pneumonia, and respiratory failure is a frequent complication particularly in patients recovering from abdominal and thoracic surgery. Physiotherapy and conventional therapeutic means like blind tracheobronchial and bronchoscopic suction applied to prevent and treat postoperative respiratory complications have been shown to not be completely effective. Minitracheotomy is a new alternative method for the treatment of sputum retention. Endobronchial suction can be performed as often as required, using a thin uncuffed tube (ID 4.5 mm) which is inserted into the trachea through the cricothyroid membrane under local anaesthesia. Since respiration occurs normally through the nose, mouth, and larynx these patients retain speech and the ability to cough. Complications are rare. Endobronchial suction via minitracheotomy is minimally invasive, more comfortable, and at least as effective as conventional bronchoscopic suction. It therefore has become a routine method used in the treatment of postoperative sputum retention in high risk patients in many intensive-care units. PMID- 1519153 TI - AIDS: a comparison of knowledge and attitudes among black, Hispanic and white Americans, 1990. AB - Increasing awareness about AIDS is an important step toward the prevention of this disease. The AIDS Knowledge and Attitudes Survey of the National Health Interview Survey shows that more than 80 percent of U.S. adults are familiar with the major modes of AIDS transmission. Despite this, up to one-third still believe that AIDS can be spread by various forms of casual contact. In the three racial/ethnic groups studied, the less educated were less knowledgeable. Further, black and Hispanic adults lagged somewhat behind white adults in certain important aspects of AIDS knowledge. About one-fourth of white, black and Hispanic adults have had the HIV antibody test. While reasons for testing differed, most of the adults were tested in health care sites. Educational counseling that should accompany HIV testing is provided to less than half of those tested. Identifying gaps in knowledge can help to more effectively target AIDS educational efforts. PMID- 1519154 TI - AIDS: a need for ongoing education. PMID- 1519155 TI - Cancer risk and prevention update. PMID- 1519156 TI - Changing racial composition of metropolitan areas. AB - In the past decade, the number of Hispanics and Asians or Pacific Islanders residing in the largest metropolitan areas increased by a remarkable 60 percent and 127 percent, respectively. In April 1990, there were 4.9 million persons of Asian or Pacific Islander origin and 14.1 million of Hispanic background living in the 25 most populous urban centers; they constituted roughly two-thirds of the nation's total population of these ethnic groups. For the most part, the destinations of these newcomers were primarily the big metropolitan areas of the West and Southwest regions of the country, although the urban centers of the Northeast and North Central attracted large numbers. By contrast, in this period the number of blacks--the largest minority group--rose by only one-seventh. PMID- 1519157 TI - Selected demographic and health characteristics--state variations, 1988-1991. AB - There is considerable regional variation in the distribution of persons over age 65, living on Social Security, living below the poverty level and with no health insurance. For the most part, such differences are reflected in low per capita income, low health care spending as well as less favorable health outcomes and health system utilization. These differences and disparities underscore the importance of considering a wide range of variables when drawing conclusions about the nation's health care system and when making policy decisions on various social programs. PMID- 1519158 TI - Use of survey data in a corporatewide health promotion program: The MetLife experience. AB - MetLife developed a corporate-wide health promotion program based on a survey of its employees, its local management, and its medical personnel. The survey's goals were to determine the wellness topics of greatest interest to employees, as well as topics believed by local management and medical personnel to be of greatest need. There was surprising unanimity concerning what employees said they wanted and what managers and medical personnel believed were needed. Stress management--including relaxation techniques and time management skills--was high on all three surveys, as were the basic of nutrition, exercise, healthy aging, cancer, and men's and women's health issues. PMID- 1519159 TI - In-vivo measurements of early and late effects in normal tissue after abdominal X irradiation--development of a clinically orientated score for the determination of side-effects and the individual radiation response in a mouse model. AB - Heiligenberger mice received abdominal single X-ray doses of either 10 or 12 Gy. Early (up to one month) and late effects (two to eight months) were measured in vivo with ten parameters (nitrite, albumin, glucose, urobilinogen, bilirubin, haemoglobine, ketone, pH, weight development, general clinical conditions). These parameters permit the assessment of the condition of the essential organ systems. Thus, their use as screening parameters appears meaningful. By creating indices and integrating these in the animal index (range 1 to 3) it is possible to obtain an impression of the health condition of the individual animal. Early and late damage can be determined with certainty despite large individual variances. Radiation-induced chronic but not lethal changes can be measured. A large early damage is also predictive for a large late morbidity; not the individual parameters allow conclusions to be drawn but instead only the total number of the parameters used here are capable of this. The results have tended to show that the systematic listing of early responses also allows for very early indication of late morbidity or chronification events to be expected. The results have shown that the individual analysis of single parameters can give rise to important indications for a decisive diagnosis. This corresponds to the usual clinical procedure and can be applied to animal experiments without restriction. PMID- 1519160 TI - Vascular patterns of tumors: scanning and transmission electron microscopic studies on human xenografts. AB - The tumor vascular system plays a significant role both in tumor growth and metastasis as well as in therapy. However, there are comparatively few papers dealing with the morphology and architecture of tumor vascularity. This is inconceivable insofar as structural and architectural parameters determine tumor blood flow. Therefore, the vascular system of eight human tumor lines transplanted onto 121 thymus-aplastic nude mice was studied with light, scanning and transmission electron microscopy as well as microvascular corrosion casting. All tumors show a connective tissue-like capsule with a dense plexus of vessels forming a "vascular envelope". Particularly in early stages, these vessels follow a tortuous course with glomeruloidal arrangement and numerous indications of angiogenic activity. In the tumor centre regular arteries and veins are never to be seen. Instead, all vessels show a capillary wall construction with variations in height and electron densities of the endothelial cells. Changes in vessel diameter, lack of vascular hierarchy, blind ends as well as irregular sinusoidal systems originating from and draining to veins are common features. The vascular densities vary considerably within single tumors. Based on the vascular architecture and wall construction, necroses may occur even in areas with intervascular distances of only 15 microns. No significant differences in vascular architecture of the various cell lines could be observed. PMID- 1519162 TI - 4th International Symposium on IORT. Munich, September 13-16, 1992. Abstracts. PMID- 1519161 TI - Follow-up data of our pilot study on concomitant hyperfractionated radiotherapy and cisplatinum (CDDP) in patients with advanced cancer of the head and neck. AB - Since 1988, 52 patients with stage III/IV squamous cell cancer of the head and neck have been treated by concomitant irradiation with 2 x 1.2 Gy/d on five days per week up to a total dose between 72 and 76.8 Gy without split and 5 x 20 mg/m2 cisplatinum (CDDP) as short infusion finished approximately 30 min before the second session on five days of the first and the fifth week of radiotherapy. Radiotherapy has been suspended after 30 and 50 Gy in three patients for insufficient response. In all other patients, radiotherapy has been completed. Due to a slow haematologic recovery, 34% of the patients received only one cycle of CDDP Grade 3 mucositis, occurring during radiotherapy in all patients, healed in a couple of weeks after radiotherapy. Three patients have a persisting ulcer between eight and 36 months after radiotherapy with biopsies negative for tumour and also no other signs of tumour. The ulcers are situated in the region of the former primary tumour with an extensive destruction of tissue already before radiotherapy (cumulative risk of this complication after three years 8%). There were no other major complication. Cumulative local control after three years was 67% (75% including salvage surgery in two patients) with a plateau after twelve months. Total survival after three years was 62%. For the whole follow-up period, local control in the region of the primary tumour after radiotherapy was: 19/29 (T4), 10/15 (T3), 7/10 (T1 + 2, including salvage surgery: 8/10). Local control in the region of the nodal metastasis after radiotherapy was: 5/14 (N3, including salvage surgery: 6/14). 18/21 (N2) and 6/8 (N1). PMID- 1519163 TI - Acute cholangitis. PMID- 1519164 TI - Current surgical management of severe intraabdominal infection. PMID- 1519165 TI - Rapid bedside method to assess changes in postoperative fluid status with bioelectrical impedance analysis. AB - BACKGROUND: Estimates of daily postoperative fluid balance usually rely on properly recorded inputs, outputs, and daily weights or clinical signs. These may be imprecise (when poorly done) and are often considered tedious to perform. METHODS: We used bioelectric impedance analysis (BIA) to assess changes in body water shifts in cardiac patients after surgery. Nine consecutively admitted patients undergoing coronary artery bypass (seven men and two women; age range, 43 to 67 years) were studied. Body weight, fluid intake and output, and BIA variables (resistance and reactance) were measured daily. Relationships between body weight and changes in resistance and reactance and net change in fluid balance (in liters per day) were evaluated statistically by regression analysis. RESULTS: Mean body weights changed significantly, reflecting early operative fluid accumulation and later postoperative diuresis; net fluid balance correlated poorly (r = 0.48; p less than 0.05) with body weight, whereas both resistance (r = -0.82; p less than 0.001) and reactance (r = -0.92; p less than 0.0001) correlated highly with net fluid balance. CONCLUSIONS: BIA is useful as an accurate, rapid bedside method for assessing changes in hydration status sequentially after surgery in cardiac patients with complicated fluid shifts. PMID- 1519166 TI - Hypercaloric glycerol in injured patients. AB - BACKGROUND: This study investigates the effects of glycerol as a fuel source in the hypermetabolic patient (after injury). METHODS: Twenty-two patients were studied after multiple trauma and randomly assigned to either glucose or glycerol as the carbohydrate source (220 gm glycerol or 320 gm dextrose) during a lipid based system of parenteral nutrition. In the immediate postoperative period, measurements were made of nitrogen balance, substrates, energy expenditure, insulin, glucagon, and liver function tests. RESULTS: In the glycerol group glucose concentrations in plasma were significantly lower, whereas glycerol levels increased nearly twentyfold. Insulin and glucagon levels increased in both groups; however, the rise in insulin level was greater in the glucose group, whereas glucagon increased in both groups to a similar degree. Nitrogen balance was restored to equilibrium in the glycerol group while remaining negative in the glucose group. No abnormalities in liver function test results or differences in serum albumin levels were noted in either group. A 12% thermic effect was noted in the glucose group but not in the glycerol group. CONCLUSIONS: Glycerol seems to be a viable fuel source in the traumatized patient, being associated with nitrogen retention and minimal thermal effect. A marked rise in plasma levels of glycerol does occur, but this does not appear to have any associated toxicity. PMID- 1519167 TI - Split-liver orthotopic liver transplantation: how to divide the portal pedicle. AB - It is possible to obtain two good-quality hepatic transplants from a single cadaveric liver by separation of right and left lobes of the liver or section between the left medial segment and the left lateral segment medial to the umbilical cleft. We attempt to define the ideal basis of separation of the structures of the portal pedicle, based on anatomic study of 25 livers. Ideally, the following should be sectioned: the left portal vein, longer and more constant than the right; the right branch of the hepatic artery, larger and more constant than the left; and the left hepatic duct, being aware of the vascularization of the common hepatic duct. Use of the left portal vein necessitates the interruption of all left venous portal branches of segment I, which should be systematically resected. A section between the left medial segment and the left lateral segment interrupts all portal venous branches of the left medial segment, which should then be resected. Before hepatic division, a cholangiogram and arteriogram are indispensable to detect variations and avoid an extensive dissection that may endanger bile duct vascularity. PMID- 1519168 TI - Etiology and management of respiratory complications after repair of esophageal atresia with tracheoesophageal fistula. AB - This article reviews the cause and management of respiratory symptoms after repair of esophageal atresia with tracheoesophageal fistula (TEF). Postoperative respiratory symptoms developed in 31 (46%) of 68 patients and included apnea and bradycardia, respiratory arrest, aspiration, and recurrent pneumonia. The respiratory symptoms were initially attributed to gastroesophageal reflux (GER) in 20 patients (64%), tracheomalacia in 4 patients (13%), recurrent TEF in 4 patients (13%), and anastomotic stricture in 3 patients (10%). Three patients with GER and the three patients with a stricture were initially managed nonoperatively. The remaining 25 patients underwent surgical correction of the underlying cause of the respiratory symptoms. Despite aggressive management of this problem, 14 (45%) of these 31 patients had persistent or recurrent respiratory symptoms. Although GER is the most common cause of respiratory complications in patients who have undergone prior TEF repair, other factors are often responsible for these symptoms and should not be overlooked. PMID- 1519169 TI - Late swallowing and aspiration problems after esophagectomy for cancer: malignant infiltration of the recurrent laryngeal nerves and its management. AB - One hundred eleven patients who underwent esophagectomy for squamous carcinoma of the esophagus were followed up during a 42-month period. Forty-three patients who had normal swallowing in the postoperative period had recurrent dysphagia on follow-up. The causes were benign anastomotic stricture (n = 15), malignant anastomotic recurrence (n = 2), recurrent laryngeal nerve palsy (n = 22), and no known cause (n = 4). Twenty-six patients were assessed by laryngoscopy and 15 were deemed suitable for Teflon injection of the vocal cord. All but one patient had improved swallowing and phonation after the procedure. Mean survival time after Teflon injection was 5 1/2 months. A significant proportion of swallowing problems after esophagectomy are not caused by mechanical obstruction. Teflon injection of a unilateral paralyzed vocal cord provides good palliation in these patients. PMID- 1519170 TI - A prospective study of the value of core needle biopsy and fine needle aspiration in the diagnosis of soft tissue masses. AB - We prospectively sampled 38 large soft tissue masses in 37 patients with both core needle biopsy (CNBX) and fine-needle aspiration (FNA) to determine the diagnostic utility of these biopsy methods. In 27 cases the histologic diagnosis made from the resected specimen was compared with the diagnosis based on the biopsy. CNBX correctly identified 16 of 16 malignant sarcomas and 10 of 11 benign masses (one was indeterminate). The grade of the sarcoma was determined correctly in every case. There were no false malignant or false benign CNBX diagnoses. FNA correctly classified 12 of 14 malignant sarcomas and four of 11 benign lesions. Diagnoses based on FNA were limited by a high proportion of samples, especially from benign lesions, that were inadequate for definitive diagnosis and by an inability to grade many malignant sarcomas. There were no significant complications resulting from the biopsies. We conclude that CNBX is a highly accurate, easily performed method for the diagnosis of large soft tissue masses that can be accomplished with minimal morbidity. PMID- 1519171 TI - Photoplethysmography reexamined: lack of correlation with duplex scanning. AB - In a prospective study a comparison was made between the results of photoplethysmography and ultrasonic duplex scanning in 151 consecutive legs with swelling, aching, and suspected venous insufficiency. Thirty-four percent of the legs had a history of previous deep venous thrombosis, 26% had undergone previous superficial vein surgery, and 11% had active or healed ulceration. Photoplethysmographic findings were normal in 86 (57%) of these legs and indicated deep venous disease in 33 (22%). With duplex scanning, incompetent vein segments were found in 140 legs (93%). The kappa coefficient of agreement between the result, classified as either normal, superficial disease only, or deep incompetence, was 0.12 +/- 0.06. In legs with superficial disease, the number of incompetent levels was no greater in legs with abnormal results of photoplethysmography than in legs with normal results of photoplethysmography. In general, an abnormal photoplethysmographic result is related to multilevel reflux and the presence of visible skin changes. Photoplethysmography had the same value, in these patients, to predict the presence of multilevel reflux as had inspection of the skin of the goiter area. These results do not warrant the continued use of photoplethysmography for surgical decision making in patients with suspected venous insufficiency. PMID- 1519172 TI - The effect of various sympathomimetics on the regional circulations in hyperdynamic sepsis. AB - Because sepsis is characterized by a depression in vascular reactivity, we hypothesized that changes in organ blood flows (Q) would differ between the nonseptic and septic state during the infusion of sympathomimetics. Therefore we examined the (sepsis x organ Q) interaction during the infusion of five sympathomimetics in 36 mature, awake sheep before and after cecal ligation and perforation produced hyperdynamic sepsis. A 3-hour infusion of dobutamine, norepinephrine, dopamine, dopexamine, or salbutamol was compared with that of placebo during both nonseptic and septic studies; drug infusion was titrated to an increase in cardiac index of greater than 20%. Increased plateau infusion doses of norepinephrine (+305%), salbutamol (+275%), dopamine (+70%), and dobutamine (+49%) were required to achieve predefined treatment guidelines during the septic versus nonseptic study. Few differences in the regional effects of individual sympathomimetics were found in the nonseptic study, although infusion of sympathomimetics was accompanied by a redistribution of systemic Q toward the heart and away from the brain, kidney, small intestine, liver, and pancreas. In the septic study, however, the sympathomimetic infusions were not accompanied by the redistribution of Q away from small intestine and liver that was demonstrated in the nonseptic study. Therefore (1) the depressed vascular reactivity in hyperdynamic sepsis altered the dose profile of exogenous sympathomimetics required to augment systemic Q, and (2) the (sepsis x sympathomimetic) interaction was characterized by a depression in the anticipated redistribution of organ Q from "nonvital" to "vital" circulations. PMID- 1519173 TI - Functional analysis of monocyte activity through synthesis patterns of proinflammatory cytokines and neopterin in patients in surgical intensive care. AB - This study was designed to further differentiate monocyte behavior in critically ill patients with operative or accidental trauma. The patient population studied consisted of 39 patients (17 patients undergoing elective surgery [ES], seven patients with major multiple injuries [MI], and 15 patients in an acute septic state [S]). Immunologic parameters assessed included monocyte phenotyping with the monoclonal antibody LeuM3, measurement of the cytokines interleukin (IL)-1, IL-6, and IL-8 in lipopolysaccharide-stimulated in vitro cultures of mononuclear leukocytes (PBMCs), and determination of neopterin in gamma-interferon-stimulated in vitro cultures and corresponding serum samples. Serum neopterin levels were very high in S patients (89.0 nmol/L; p less than 0.05) compared with control values (4.6 nmol/L), with a rise to 16.4 nmol/L in ES patients on day 7 and 13.4 nmol/L in MI patients on day 7. The concentrations of gamma-interferon-induced neopterin in the supernatants of the PBMC cultures were elevated in all patient groups. Severe impairment of IL-1 synthesis was seen in MI and S patients. IL-8 synthesis (818 +/- 150 units/ml, control value) was also suppressed (p less than 0.05) in MI patients; the values were 135 +/- 65 units/ml on day 1,231 +/- 110 units/ml on day 3,347 +/- 131 units/ml on day 7, and 355 +/- 107 units/ml in S patients. The kinetic patterns of synthesis were comparable for IL-1 and IL-8 in all patient groups. Lipopolysaccharide-induced IL-6 synthesis (9.4 +/- 1.5 x 10(3) units/ml, control value) was significantly elevated in the PBMC cultures of all patient groups, with the exception of the early phase after accidental trauma. Maximum amounts of IL-6 synthesis after surgery were 19.6 +/- 7 x 10(3) units/ml in S patients and 19.0 +/- 2.2 x 10(3) units/ml in ES patients. These results demonstrate (1) the impairment of the functional capacity of circulating monocytes and (2) that the degree of functional impairment is proportional to the severity of the injury. PMID- 1519174 TI - Correction of steal syndrome secondary to hemodialysis access fistulas: a simplified quantitative technique. AB - Correction of symptomatic vascular steal distal to an arteriovenous fistula requires either fistula ligation or banding. Ligation carries the obvious disadvantage of destruction of a functioning angioaccess, whereas banding procedures have been plagued by the complexity of many of the reported techniques and by the difficulty of balancing fistula flow with distal perfusion. In this study a simple plication technique is described that avoids the introduction of any additional foreign material and that quantifies distal perfusion by means of intraoperative pulse volume recordings. Five patients have been treated by this method, two with autologous vein fistulas and three with bridge fistulas using polytetrafluorethylene. All five have had resolution of their ischemic symptoms with an increase in intraoperative pulse volume recordings of 5 mm or more. Only three of the patients had restoration of the radial pulse, which was not a specific end point of the banding procedure. Furthermore, all fistulas remained patent for at least 6 months and continued to provide adequate flows for hemodialysis. Banding/plication is clearly preferable to fistula closure for the management of steal syndrome. The method described herein is simple and hemodynamically identifies the minimal constriction that will resolve symptoms and preserve fistula flow. PMID- 1519175 TI - Fetus in fetu removal in a 47-year-old man. AB - A case of removal of a fetus in fetu in a 47-year-old man is reported. The patient had an upper abdominal mass since birth that had never caused any subjective symptoms. A preoperative computed tomographic scan was useful to confirm the diagnosis. The operative specimen consisted of a cystic mass about 20 cm in diameter, situated in the upper retroperitoneal space. The cyst was full of a yellowish fluid and hairs. A bony structure, about 10 cm in diameter, contained a vertebral axis connected to the ribs and was adherent to the cystic wall. To our knowledge this is the first reported case of fetus in fetu described in an adult man. The tumor, present for 47 years, did not grow or cause any complications and did not show any sign of malignancy. PMID- 1519177 TI - Re: Diagnosis and management of parathyroid diseases. PMID- 1519176 TI - An embolizing lesion in a minimally diseased aorta. AB - A case report of a patient with an unusual source of emboli resulting in acute limb-threatening ischemia is presented. Diagnostic angiography of the lower extremity was performed, followed by thromboembolectomy, which successfully restored normal arterial flow to the threatened leg. After surgery the patient underwent transesophageal echocardiography, which failed to identify an embolic source. Because of the high degree of clinical suspicion that the primary disease process was embolic rather than thrombotic, a thorough evaluation of the arterial tree was performed, including computed tomography and aortography. A large, mobile intravascular lesion arising from a normal descending thoracic aorta was identified and successfully treated with resection and graft placement. PMID- 1519178 TI - Re: The glands of Owen. PMID- 1519179 TI - [Diagnosis and treatment of paroxysmal tachycardia]. AB - The practising physician's knowledge of paroxysmal attacks of tachycardia is frequently disappointing. In this article a description is given of mechanisms and possible sites of origin of tachycardia. This is followed by a discussion on the typical history and the findings in these patients. Lastly, therapeutic guidelines are given. A discussion of the electrocardiographic features of the different types of paroxysmal tachycardias falls outside the scope of this article. PMID- 1519180 TI - [Diagnosis of cardiac arrhythmias in general practice]. AB - Cardiac arrhythmias represent a common diagnostic and a frequent therapeutic problem (table 1). They occur both in cordially sound people and in patients with a basic cardiac disease, their clinical significance reaching, therefore, from harmless to life-threatening episodes. For this reason, a documentation and characterization of the different arrhythmias is necessary in clinical practice in order to be able to initiate an adequate therapy in symptomatic and particularly in prognostically relevant cardiac arrhythmias. PMID- 1519181 TI - [Drugs in atrial fibrillation]. AB - The initial therapy of atrial fibrillation is guided by the clinical symptomatology of the patient. Acute atrial fibrillation at a rapid ventricular rate is an emergency situation. Pharmacological therapy is aimed to delay atrioventricular conduction and thereby slow the ventricular rate. A new and interesting therapeutical option to induce conversion to sinus rhythm is the intravenous administration of class-Ic drugs. The conversion rate of patients with nonvalvular atrial fibrillation of recent onset is high and accounts up to 90%. Patients with atrial fibrillation have an increased incidence of ischemic stroke. Anticoagulation, i.e. administration of aspirin in patients under 70 years of age, can reduce the occurrence of cerebral ischemic event. PMID- 1519182 TI - [Drug therapy of atrioventricular tachycardia]. AB - All types of antiarrhythmic drugs are suitable for the treatment of junctional and AV-reentry Tachycardias. Betablocker, calcium antagonist and digitalis are mainly influencing the conductivity in the AV node, leaving other structures unaltered. In contrast, class-antiarrhythmic drugs slow conduction and prolong the refractor effect in the accessory pathway. In addition, drugs of subclass 1c can influence especially the 'fast' pathway in dual AV-node conduction. Class-3 drugs prolong refractoring in all compartments of the heart by preventing re entry in both, AV nodal tachycardias and AV re-entry in the WPW syndrome. The clinical indication for one of these drugs is mainly influenced by the potential side-effects and by pharmacokinetic considerations. PMID- 1519183 TI - [Drug prevention and therapy of ventricular tachycardia]. AB - Antiarrhythmic drugs of type I to IV (Vaughan Williams) are generally used for the treatment of ventricular tachycardia, especially in patients with symptomatic and hemodynamically not tolerated arrhythmias; however, randomized controlled studies revealed a beneficial effect on sudden cardiac death only for type-II (beta-blocking agents) and type-III (Amiodarone) antiarrhythmic drugs. These drugs are, therefore, the antiarrhythmic agents of first choice; but, in addition, underlying heart disease, triggering factors and heart-rate dependency should be considered. PMID- 1519184 TI - [Ventricular late potentials--methods and clinical importance]. AB - Ventricular late potentials are due to regionally depressed inhomogenous conduction, mainly in the border zone of a previous myocardial infarction. They can be recorded noninvasively using high-resolution signal-averaging techniques. They are almost never detectable in normals, whereas they represent a frequent finding in postmyocardial infarction patients. The presence of ventricular late potentials after previous myocardial infarction predicts the subsequent occurrence of hemodynamically severe sustained ventricular tachycardia and/or sudden cardiac death. Their predictive significance can be increased by combining signal-averaging with long-term ECG recording and estimates of left-ventricular ejection fraction. However, despite recent major improvements in identification of patients at risk, there is still a need for an effective mode of prevention of serious ventricular tachyarrhythmias after myocardial infarction. PMID- 1519185 TI - [Who should be referred for electrophysiologic studies?]. AB - Prerequisite of a rational antiarrhythmic therapy is the correct diagnosis of the given cardiac rhythm disorder. The majority of intermittent and latent cardiac arrhythmias can be reliably induced and analyzed during the electrophysiologic study (EPS). In case of bradyarrhythmias, the method is indicated in patients with suspected sinus node disease or high-grade AV conduction disturbances, as far as the cause of clinical symptoms cannot be settled by Holter recordings. Since patients with paroxysmal supraventricular tachycardias (WPW syndrome and AV nodal reentrant tachycardia) can be cured by transvenous ablation techniques, EPS is indicating in this setting in all symptomatic patients for the diagnosis and the treatment of the given arrhythmia. In patients with recurrent ventricular tachyarrhythmias, EPS should be performed to establish the diagnosis and to control medical treatment; in addition, EPS is a prerequisite for nonpharmacologic treatment modalities such as defibrillator therapy and transvenous or surgical ablation techniques. In survivors of cardiac arrest without new Q-wave myocardial infarction, persistent ventricular tachyarrhythmias can be induced in some 50% of the patients. Patients should be evaluated by EPS in case the reasons for significant clinical symptoms cannot be determined otherwise, given the likelihood, that brady- or tachyarrhythmias are the cause of the clinical symptoms; this includes patients with organic heart disease and with unexplained syncopes. PMID- 1519186 TI - [Surgery of tachycardic cardiac arrhythmias. Surgical treatment of life threatening tachycardias: indications, surgical possibilities, results]. AB - Electrophysiologic operations for surgical treatment of malignant tachyarrhythmias include a preoperative electrophysiologic study (EPS) to assess the characteristics and dignity of the arrhythmia, intraoperative electrophysiologic mapping to identify and localize the arrhythmogenic morphologic substrate, surgical ablation of the arrhythmogenic tissues, and early postoperative EPS to evaluate the result of the operation and the post-surgical prognosis. The majority of patients undergoing an electrophysiologic operation suffer from supraventricular tachyarrhythmias due to accessory atrioventricular bypass tracts (Wolff-Parkinson-White syndrome) and malignant ventricular tachycardias in the setting of coronary artery disease. In comparison of the natural (non-surgical) history of those rhythm problems their prognosis as regards mortality and morbidity is significantly improved by operation. Possibly the spectrum and the role of electrophysiologic antiarrhythmic surgery will be changed during the next decade by the increasing application of interventional cardiologic measures as catheter ablation (PTCA) thrombolysis. PMID- 1519187 TI - [Clinical assessment and indications for automatic defibrillation]. AB - A variety of therapeutic options including pharmacological treatment, surgical procedures, ablation interventions and electrotherapy are available for the management of patients who are subject to symptomatic ventricular tachyarrhythmias. Patients with documented sustained ventricular tachycardia or ventricular fibrillation are usually controlled by serial electrophysiological studies. About 30 to 60% of these patients respond to antiarrhythmic drugs during serial electrophysiological testing. Patients with severe left-ventricular function respond less frequently than those of well-preserved function. Long-term follow-up studies have demonstrated that, if ventricular tachyarrhythmias can no longer be induced on antiarrhythmic drugs or if inducibility is at least rendered more difficult, the rate of recurrences is low. In contrast, patients with still inducible ventricular tachyarrhythmias may have a poor prognosis and may suffer from frequent recurrences or may even die suddenly. Thus, nonpharmacological strategies such as an implantable cardioverter/defibrillator, transvenous catheter ablation and map-guided antitachycardia surgery have become important alternatives for drug refractory patients. Since the introduction of the implantable cardioverter/defibrillator using a nonthoracotomy approach, the intraoperative and perioperative mortality and morbidity has been significantly reduced. A widespread use of these newer devices required the establishment of guidelines for the appropriate application of this new treatment modality. Surgical, medical and economic considerations make it imperative that defibrillator therapy should be chosen on a basis of careful patient selection. The presenting clinical arrhythmia and its hemodynamic stability, underlying heart disease and left-ventricular ejection fraction should be taken into consideration.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1519188 TI - Nutritional support in chronic obstructive lung disease. PMID- 1519189 TI - Microscopic and macroscopic measurements of emphysema: relation to carbon monoxide gas transfer. AB - BACKGROUND: Studies of the relation between the severity of structural change in emphysema and physiological abnormality have been based on macroscopic assessments, which have not been truly quantitative or sensitive enough to detect early changes. With a highly reproducible method for measuring emphysema using histological sections and a semiautomatic image analysis system, this quantitative assessment of emphysema was compared with a semiquantitative macroscopic assessment of emphysema and measurements of carbon monoxide gas transfer. METHODS: Microscopic and macroscopic measurements of emphysema on 44 thoracotomy specimens were compared; only two were from non-smokers. Airspace wall surface area per unit volume was measured microscopically with an automatic image analyser and expressed as both the mean airspace wall surface area per unit volume and the mean value of the five fields with the lowest values. Macroscopic emphysema was measured directly on a tracing of the midsagittal slice using a digitising tablet attached to a microcomputer and expressed as a percentage of the total area of lung. In cases with centriacinar emphysema the number of discrete lesions was counted. RESULTS: The area of macroscopic emphysema ranged from 0 to 78% of the total area of lung examined, but most patients had less than 1% involvement so that the distribution was highly skewed. Both mean airspace wall surface area per unit volume and the mean of five fields with the lowest airspace wall surface area per unit volume were normally distributed, with mean airspace areas ranging from 8.8 to 25.4 mm2/mm3 (mean 18.1 mm2/mm3). In lobes with centriacinar emphysema the number of discrete lesions correlated with airspace wall surface area per unit volume and with preoperative carbon monoxide transfer factor (TLCO) per unit lung volume. However, other measurements of macroscopic emphysema did not correlate with loss of alveolar wall surface area, and there was considerable overlap between subjects with no or minimal macroscopic emphysema and those with more severe disease. TLCO correlated with both mean airspace wall surface area per unit volume and the mean of five fields with the lowest airspace wall surface area per unit volume but not with the severity of macroscopic emphysema. CONCLUSION: If emphysema is to be quantified it must be measured microscopically; macroscopic measurements do not, in general, reflect the microscopic loss of airspace wall. PMID- 1519190 TI - Somnofluoroscopy, computed tomography, and cephalometry in the assessment of the airway in obstructive sleep apnoea. AB - BACKGROUND: Assessments of the upper airways in patients with the obstructive sleep apnoea syndrome are usually carried out on awake patients who are upright. The dynamics of the airway in a patient who is asleep and lying down may be different. METHODS: Somnofluoroscopy, computed tomography of the upper airway, and cephalometry were carried out in 11 patients with the obstructive sleep apnoea syndrome (10 male; mean (SD) age 53 (10) years) to examine the airway while they were awake and asleep. RESULTS: At somnofluoroscopy 10 patients were in stage 2 sleep and only one in REM sleep. At least five obstructive events were visualised by lateral fluoroscopy in each patient. Imaging allowed observation of the dynamics of airway collapse, which began in the oropharynx in all cases, progressing to the hypopharynx in 10 cases and to the laryngopharynx in five. At fluoroscopy the soft palate was seen to hook up during airway occlusion in 10 patients, thereby increasing its cross sectional area. It was then sucked down into the hypopharynx. Somnofluoroscopic and cephalometric findings agreed, eight of the 10 patients with hypopharyngeal collapse shown by somnofluoroscopy having an inferiorly placed hyoid bone according to cephalometry (distance from the mandibular plane to the hyoid bone (MP-H distance) increased); the one patient with no hypopharyngeal collapse had a normal MP-H. By contrast, six of the 11 patients had a normal or supranormal hypopharyngeal cross sectional area of the airway on the computed tomogram. CONCLUSIONS: Somnofluoroscopy allows examination of the dynamics of airway closure in this disorder and shows the important role of the soft palate in acting as a plug in the oropharynx. Dynamic studies are required to determine the pattern of pharyngeal obstruction in obstructive sleep apnoea. PMID- 1519191 TI - Habitual snoring with and without obstructive sleep apnoea: the importance of cephalometric variables. AB - BACKGROUND: The obstructive sleep apnoea syndrome is characterised by an increased apnoea-hypopnoea index and a reduction in the minimal arterial oxygen saturation (SaO2) values during sleep. The extent to which these variables can be predicted by cephalometric and otorhinolaryngological variables was tested. METHODS: One hundred consecutive habitual snorers (84% male), with a mean (SD) age of 50.1 (10.1) years, were studied. The 45 patients with less severe sleep apnoea, with an apnoea-hypopnoea index of 10 or less (group A), were compared with the 55 with an index above 10 (group B). RESULTS: Body mass index, some cephalometric variables, and some otorhinolaryngological variables differed significantly between group A and group B, in particular the soft tissue measures PNS-P (posterior nasal spine to palate), MP-H (mandibular plane to hyoid bone), degree of oropharynx stenosis, and tongue size. In a multiple regression correlation analysis MP-H, SNB (angle from sella to nasion to subspinale point), SNA (angle from sella to nasion to supramentale point), PAS (posterior airway space), tongue size, and body mass index contributed significantly to the equation explaining the severity of sleep apnoea. Nevertheless, these variables together explained only 33% of the variance of the apnoea-hypopnoea index in the total sample; they were more important for patients with moderate to severe stages of the disease. CONCLUSION: The lack of association between cephalometric variables and mild sleep apnoea suggests that the differences in these variables (soft tissue measures) may be the consequence rather than the cause of habitual snoring and the obstructive sleep apnoea syndrome. PMID- 1519192 TI - Validity of peak expiratory flow measurement in assessing reversibility of airflow obstruction. AB - BACKGROUND: Assessing the reversibility of airflow obstruction by peak expiratory (PEF) measurements would be practicable in general practice, but its usefulness has not been investigated. METHODS: PEF measurements were performed (miniWright peak flow meter) in 73 general practice patients (aged 40 to 84) with a history of asthma or chronic obstructive lung disease before and after 400 micrograms inhaled sulbutamol. The change in PEF was compared with the change in forced expiratory volume in one second (FEV1). Reversible airflow obstruction was analysed in two ways according to previous criteria. When defined as a 9% or greater increase in FEV1 expressed as a percentage of predicted values reversibility was observed in 42% of patients. Relative operating characteristic analysis showed that an absolute improvement in PEF of 60 l/min or more gave optimal discrimination between patients with reversible and irreversible airflow obstruction (the sensitivity and specificity of an increase of 60 l/min in detecting a 9% or more increase in FEV1 as a percentage of predicted values were 68% and 93% respectively, with a positive predictive value of 87%). When defined as an increase of 190 ml or more in FEV1, reversible airflow obstruction was observed in 53% of patients. Again an absolute improvement in PEF of 60 l/min or more gave optimal discrimination between patients with reversible and irreversible airflow obstruction (sensitivity 56%, specificity 94%, and positive predictive value 92%). CONCLUSION: Absolute changes in PEF can be used as a simple technique to diagnose reversible airflow obstruction in patients from general practice. PMID- 1519193 TI - Single breath transfer factor for carbon monoxide in an asymptomatic population of never smokers. AB - BACKGROUND: Data on reference values of transfer factor variables in general populations of asymptomatic never smokers are limited. The aim of this study was to examine the relation between test variables and age, height, haemoglobin concentration and carboxyhaemoglobin concentration. METHODS: Measurements of single breath transfer factor for carbon monoxide (TLCO) were obtained for a randomly selected sample of never smokers in north western Europe who were 18-73 years old and had no respiratory symptoms or disorders. Two recordings of TLCO with a ratio of inspiratory vital capacity to forced vital capacity of greater than 0.09 were obtained by standardised techniques for 304 subjects. RESULTS: The measurement errors expressed as a percentage of the common mean value of TLCO, volume adjusted TLCO (KCO), and alveolar volume (VA) were 4.5%, 4.2%, and 2.4% respectively. Multiple linear regressions showed sex specific effects of height and age on TLCO, and, in addition, of haemoglobin and carboxyhaemoglobin concentrations on KCO. VA was associated with height but not with age. The 5th and 95th centiles for TLCO and KCO in men and women were between 78% and 82% and between 120% and 127%, respectively, of predicted values when age and height were taken into account. CONCLUSION: Reference equations and normal values for transfer test variables in a large healthy population of never smokers are described in relation to age, height, and haemoglobin concentrations. To our knowledge, this is the first report of an association between carboxyhaemoglobin concentrations and KCO in a population of never smoking men and women. PMID- 1519194 TI - Localised pulmonary metastatic calcification associated with pulmonary artery obstruction. AB - BACKGROUND: Metastatic pulmonary calcification, a complication of uraemia and disordered calcium metabolism, may be diffuse or localised. The factors that determine calcium precipitation are complex, but tissue alkalosis is thought to be important. As obstruction of the pulmonary artery theoretically causes local alkalosis a retrospective necropsy study was carried out to examine the relation between metastatic pulmonary calcification and vascular obstruction. METHODS: Five patients with focal and two with diffuse metastatic calcification in the lungs were identified over eight years. Lungs were studied macroscopically and by light microscopy, haematoxylin and eosin and histochemical stains being used for calcium. RESULTS: Underlying risk factors for calcification in these patients included renal failure in six and disseminated malignancy in five. In the five patients with localised calcification obstruction of the pulmonary artery by thrombus or tumour was found proximal or adjacent to areas of calcium deposition. In two patients metastatic calcification was confined to a lung with unilateral pulmonary artery thromboembolic occlusion. Calcification was not specifically associated with infarction, pneumonia, or diffuse alveolar damage. Lesions of the pulmonary artery were not seen in the two patients with diffuse bilateral metastatic calcification. CONCLUSION: In this small series there was a spatial association between pulmonary artery obstruction and localised metastatic calcification. It is proposed that pulmonary artery obstruction alters the microchemical environment of the lung, favouring tissue alkalosis and thereby enhancing parenchymal calcification in patients predisposed to this condition. PMID- 1519195 TI - Surgical closed pulmonary valvotomy for critical pulmonary stenosis: implications for the balloon valvuloplasty era. AB - BACKGROUND: Closed pulmonary valvotomy for critical pulmonary stenosis has no apparent advantage over the percutaneous balloon technique, though it is used when balloon valvuloplasty fails. Experience of this technique at the Heart Institute, Tel Hashomer, since it was first used in 1973 has been reviewed. METHODS: Thirty eight infants up to 1 year old (25 of them neonates--that is, nil to 1 month old) with critical pulmonary stenosis were operated on from 1973 to 1989. All had a transventricular valvotomy, by a modification of the Brock method, and all underwent cardiac catheterisation before surgery. RESULTS: Five of the 25 neonates (20%) died, but none of the other infants, so that the total mortality (five out of 38) was 13%. Three of the 38 required an aortopulmonary shunt. All 38 survivors were followed up--from one month to 14 years (mean 7.5 years). All were symptom free at the last check up. Fifteen of the survivors had required further surgery; this was successful in all cases. CONCLUSIONS: For the balloon valvuloplasty era surgical pulmonary valvotomy provides a good back up for failed attempts at percutaneous valvuloplasty. Review of outcome provides data for comparison with balloon valvuloplasty in the future. PMID- 1519196 TI - Defensins: ancient but potentially dangerous weapons in the armoury. PMID- 1519197 TI - An unusual cause of bilateral diaphragmatic paralysis. AB - In a patient who had a sudden onset of bilateral diaphragmatic paralysis after forceful neck manipulation complete, though gradual, recovery in lung function and transdiaphragmatic pressures was seen over three years. This is a previously unrecognised risk of neck osteopathy. PMID- 1519198 TI - Cystic fibrosis in a 70 year old woman. AB - A 68 year old woman with a lifelong history of chronic bronchitis was diagnosed as having cystic fibrosis. The diagnosis was based on a suggestive family history, steatorrhoea, bronchiectasis with respiratory insufficiency, and very high sweat sodium content. The patient was found to be heterozygous for the delta F 508 gene defect. PMID- 1519199 TI - Removal of endobronchial mucormycosis lesion through a rigid bronchoscope. AB - A 44 year old man with poorly controlled diabetes mellitus developed endobronchial mucormycosis, which totally obstructed the right lower lobe bronchus. The lesion was removed through a rigid bronchoscope. Two weeks later the bronchus was free of mucormycosis histologically and on culture. PMID- 1519200 TI - Horseshoe lung with left lung hypoplasia. AB - Horseshoe lung is an uncommon congenital malformation in which the bases of the right and the left lungs are fused to each other by a narrow isthmus posterior to the cardiac apex. So far 22 cases have been described: most of these were associated with right lung hypoplasia and the scimitar syndrome. A horseshoe lung anomaly with left lung hypoplasia is described. PMID- 1519201 TI - Bronchoalveolar lavage as a research tool. PMID- 1519202 TI - BOOP and COP. PMID- 1519203 TI - Vertebral fractures in steroid dependent asthma and involutional osteoporosis: a comparative study. PMID- 1519204 TI - Bronchial compression as a result of lung herniation after pneumonectomy. PMID- 1519205 TI - School microepidemic of tuberculosis. PMID- 1519206 TI - Blood viscosity and cardiovascular disease. PMID- 1519207 TI - Lupus anticoagulant activity is frequently dependent on the presence of beta 2 glycoprotein I. AB - Antiphospholipid antibodies (aPL) are defined by anticardiolipin antibody (aCL) ELISA and prolongation of phospholipid dependent coagulation assays (lupus anticoagulant; LAC). For the binding of aCL to cardiolipin a cofactor, beta 2 glycoprotein I (beta 2-GPI), is necessary. We have investigated whether the same cofactor is essential for LAC activity. Plasma from 6 LAC positive patients and 3 controls was depleted from beta 2-GPI by means of affinity chromatography. From the 6 LAC positive plasmas, 4 became LAC negative (tested with dRVVT) when beta 2 GPI was depleted and became positive again when purified beta 2-GPI (200 micrograms/ml) was added. A dose response curve showed that addition of 50 micrograms/ml beta 2-GPI to beta 2-GPI deficient patient plasma, led to a positive dRVVT. Depletion of, and addition of beta 2-GPI to plasma from controls had no effect on the dRVVT. Measurement of beta 2-GPI plasma levels in 19 LAC positive patients, 40 LAC negative patients and 15 controls showed no difference in beta 2-GPI levels. These results show that a combination of aPL and beta 2-GPI is essential not only for binding to cardiolipin, but also for LAC activity and imply that low beta 2-GPI levels (less than 50 micrograms/ml) can lead to false negative LAC tests. These observations may lead to new insights in the pathophysiological complications associated with aPL. PMID- 1519208 TI - Gemfibrozil reduces plasma prothrombin fragment F1 + 2 concentration, a marker of coagulability, in patients with coronary heart disease. AB - The effects of gemfibrozil on several indices of haemostatic activity were explored in male patients with coronary heart disease (CHD). Sixty-three of 71 patients completed a crossover study in which gemfibrozil 1,200 mg/day and matching placebo were each taken in randomised order for 2 months in a double blind manner, separated by a 2-month washout period. Serum cholesterol decreased by an average (95% confidence interval) of 12 (9 to 15)% and non-fasting triglyceride concentration by 43 (34 to 51)% during active treatment. Plasma prothrombin fragment F1 + 2 concentration, a marker of the in vivo rate of generation of thrombin, was 25 (12 to 37)% lower on average while on gemfibrozil than during the placebo phase. Factor VII coagulant activity (VIIc) and antigen concentration, and fibrinopeptide A concentration were not influenced by gemfibrozil in the group overall. However, the VIIc response appeared to be dependent upon the untreated cholesterol level. Hypercholesterolaemic men (cholesterol greater than 6.5 mmol/l) experienced a significant reduction in VIIc averaging 6% of standard during active therapy. Other effects of gemfibrozil were a 5 (2 to 9)% increase in plasma fibrinogen by a gravimetric method, an 11 (8 to 13)% increase in platelet count, and a 6 (2 to 10)% reduction in white cell count. The reduced incidence of CHD following gemfibrozil therapy in hyperlipidaemic patients may arise in part through a reduction in procoagulant activity and thus the risk of an occlusive coronary thrombosis. PMID- 1519209 TI - The use of the D-dimer test in combination with non-invasive testing versus serial non-invasive testing alone for the diagnosis of deep-vein thrombosis. AB - We studied the usefulness of the determination of plasma D-dimer levels (using an ELISA) in combination with non-invasive testing with impedance plethysmography (IPG) or real-time ultrasonography (US) for the diagnosis of deep-vein thrombosis (DVT), in outpatients with clinically suspected DVT. This combined approach was compared to serial non-invasive testing alone in these patients. The sensitivity of a positive D-dimer test (greater than 300 micrograms/l) for the presence of DVT was 100% (70/70 patients; 95% C.I.: 95-100%), whereas the specificity was 29% (69/239 patients; 95% C.I.: 23-34%). The proportion of patients in which a definitive decision about the presence or absence of DVT could be made on the day of referral, was calculated for both approaches. When applying the combined approach, in 42% of all referred patients the diagnosis of DVT could either be established or refuted on entry, as opposed to only 19% of patients using serial non-invasive testing alone. Also, the costs per DVT diagnosed were calculated for the two diagnostic approaches. For the diagnosis of DVT the costs using serial IPG were comparable to the costs using the combination of IPG and the D-dimer test. The same conclusion holds for the comparison of serial US with the combination of US and D-dimer testing. We conclude that for the diagnosis of DVT in symptomatic outpatients the combination of non-invasive testing with the D dimer test might be preferred over serial non-invasive testing alone, although the safety of such an approach remains to be established in future management studies. PMID- 1519210 TI - A randomized and blinded comparison of three bleeding time techniques: the Ivy method, and the Simplate II method in two directions. AB - We compared the Ivy bleeding time method and two alternatives of the Simplate II method (incisions in horizontal and vertical direction) with each other, with regard to the sensitivity, the specificity, the costs and the burden for the patient. In the aspirin study an aspirin-induced bleeding defect was used. Seventy-two healthy volunteers were randomized to receive either 500 mg acetylsalicylic acid (ASA) or a placebo. Double blinding was maintained throughout the study. In the anticoagulation study 62 patients participated, who received oral anticoagulants (OAC) for various reasons. All participants received two bleeding time methods. The burden for the participants of each method was screened by a small standard questionnaire. The differences in sensitivity and specificity between the three methods proved minimal. The Ivy method was more often preferred by the participants than the Simplate methods. Since a choice on the basis of sensitivity and specificity appears not possible, we prefer the Ivy method because of lower costs and less burden. PMID- 1519211 TI - Venous thrombosis during pregnancy: leg and trimester of presentation. AB - In order to determine the relative frequencies of left and right leg venous thrombosis during pregnancy and the frequencies of venous thrombosis during the three trimesters, a cohort study of 60 consecutive patients with a first episode of venous thrombosis during pregnancy was performed. Fifty-eight women had isolated left leg thrombosis, two patients had bilateral venous thrombosis and no patient had isolated right leg venous thrombosis. Thirteen patients had venous thrombosis during the first trimester (21.7%), 28 during the second trimester (46.7%) and 19 during the third trimester (31.7%). These findings indicate that patients with symptoms in the right leg rarely have venous thrombosis. Because leg pain and swelling occur most frequently during the third trimester but venous thrombosis is relatively equally distributed during all three trimesters, patients presenting earlier during pregnancy are more likely to have venous thrombosis than patients presenting later during pregnancy. PMID- 1519212 TI - In vivo significance of kinetic constants of tight binding reversible proteinase inhibitors. AB - For a reaction between an enzyme and inhibitor, rate constants and equilibrium constants are both widely used as measures of inhibitor potency. Which one of these two parameters should be used depends on the mechanism of the reaction. Moreover, for biological studies it is not always the overall effectiveness of an inhibitor that is important, but also the rate at which it acts in conditions that may be encountered in vivo. In vitro investigations may be performed to determine the kinetic and thermodynamic constants in an enzyme inhibitor system and to investigate the influence of various other effector biomolecules. However, in translating these results into physiological conclusions, care must be taken that the in vitro experiments have been properly designed and data analysed correctly. This article is an attempt to indicate some of the problems that can be encountered in this process. PMID- 1519213 TI - Effect of leukocyte proteinases on tissue factor pathway inhibitor. AB - The effect of human neutrophil elastase and cathepsin G on recombinant tissue factor pathway inhibitor (TFPI) was investigated. A weak inhibition by TFPI of both elastase (Ki = 0.4 microM) and cathepsin G (Ki = 0.1 microM) was observed. Neutrophil elastase rapidly cleaved TFPI at the Thr87-Thr88 bond situated at the link between Kunitz domains I and II. Cleavage of TFPI by cathepsin G was also observed, but the reaction was much slower and resulted in a number of fragments. Proteolytic cleavage by both elastase and cathepsin G resulted in destruction of inhibitor function with respect to TFPI's inhibition of factor Xa. Cleavage by neutrophil elastase was capable of restoring factor Xa amidolytic activity after its initial inhibition by TFPI. Inhibition of cathepsin G by TFPI was strongly augmented by stoichiometric amounts of factor Xa. However, the augmentation was temporary, presumably due to concomitant cleavage of TFPI by cathepsin G. These observations may have implications for the putative effect of neutrophil leukocyte stimulation on the regulation of the tissue factor-mediated coagulation pathway. Conversely, formation of a factor Xa/TFPI complex may reduce or modulate the proteolytic potential of stimulated leukocytes by temporary inhibition of cathepsin G. PMID- 1519214 TI - Measurement of markers of activated coagulation in antithrombin III deficient subjects. AB - Functional antithrombin III levels were measured by factor Xa inhibition in 63 members of a large family with type 2 antithrombin III deficiency and individuals were classified as antithrombin III deficient or non-deficient according to the results. F1 + 2 and TAT complexes were measured using an ELISA and FPA levels were measured by radioimmunoassay. Thirty subjects (48%) were classified as antithrombin III deficient and 33 (52%) as antithrombin III non-deficient. The mean level of F1 + 2 was significantly higher in the deficient adults (0.87 +/- 0.26) compared to both the non-deficient adults (0.70 +/- 0.21) (p = 0.03) and the deficient adults receiving warfarin (0.16 +/- 0.01) (p less than 0.001). The differences in the mean values of TAT complexes and FPA between deficient and non deficient individuals were not statistically significant. These findings suggest that untreated antithrombin III deficient subjects generate more thrombin than their non-deficient family members and that warfarin inhibits this thrombin formation. In this cross-sectional study, it is not possible to correlate the levels of the surrogate makers with future clinical outcome. PMID- 1519215 TI - Effects of splenectomy on immune thrombocytopenic purpura in (NZW x BXSB) F1 mice: analyses of platelet kinetics and anti-platelet antibody production. AB - Effects of splenectomy on platelet kinetics and production of anti-platelet antibodies were studied in male (NZW x BXSB) F1 (W/B F1) mice, which are known as the animal model of immune thrombocytopenic purpura (ITP). Studies on organ localization of radiolabeled platelets revealed that splenic uptake significantly increases in W/B F1 mice in comparison with that of normal controls. W/B F1 mice showed a significant increase in platelet counts and, in contrast with sham operated controls, high levels of platelet counts were maintained up to 6 weeks after splenectomy. Platelet lifespans (PLSs) did not reach normal levels, although prolonged PLSs were observed. In addition, platelet-associated antibody (PAA) values showed a tendency towards transient decrease, but there was no change in platelet-bindable serum antibodies (PBAs). These findings indicate that the suppression of anti-platelet antibody production is essential to the treatment of ITP; splenectomy may not be effective in treating severely affected ITP patients because, although the spleen is one of the major sites of platelet sequestration and antibody production, reticulo-endothelial systems (RESs) (liver, bone marrow, lymphnodes, etc.) other than the spleen are also responsible for the destruction of platelets. We therefore consider the W/B F1 mouse to be a useful model of human ITP, and believe that it provides valuable information for the development of new therapeutic agents in patients with ITP, especially those who do not respond to splenectomy. PMID- 1519216 TI - Membrane fluidity is related to the extent of glycation of proteins, but not to alterations in the cholesterol to phospholipid molar ratio in isolated platelet membranes from diabetic and control subjects. AB - Platelets from diabetic subjects are hypersensitive to aggregating agents in vitro. Membrane fluidity modulates cell function and we previously reported reduced membrane fluidity associated with hypersensitivity to thrombin in intact platelets from diabetic subjects. Reduced membrane fluidity and hypersensitivity to agonists has also been reported in platelets from non-diabetic subjects whose platelets have an increased cholesterol/phospholipid molar ratio. Glycation of platelet membrane proteins is enhanced in diabetic subjects, and could contribute to the decreased membrane fluidity in these platelets. We examined the relation among fluidity, cholesterol/phospholipid molar ratio, and glycation of proteins in isolated platelet membranes from diabetic and control subjects. Seven poorly controlled diabetic subjects were compared with 7 age- and sex-matched control subjects. The mean steady-state fluorescence polarization value in 1,6-diphenyl 1,3,5-hexatriene-labeled isolated platelet membranes from diabetic subjects (0.184 +/- 0.004) was significantly greater than from control subjects (0.171 +/- 0.004, p less than 0.01); thus, fluidity in platelet membranes from diabetic subjects is decreased. Reduced fluidity in platelet membranes from diabetic subjects could not be attributed to changes in the cholesterol/phospholipid molar ratio. Total or very low density (VLDL), low density (LDL), or high density (HDL3) lipoprotein cholesterol concentration in plasma was not significantly different between groups, but the ratio of VLDL+LDL to HDL2 + HDL3 cholesterol was significantly greater in diabetic subjects (4.79 +/- 0.73) than in control subjects (2.54 +/- 0.30, p less than 0.02). Proteins were glycated significantly more extensively in platelet membranes from diabetic subjects (25.5 +/- 0.9 nmol glucose/mg protein) than those from control subjects (21.0 +/- 0.6 nmol glucose/mg protein, p less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1519217 TI - Assessment of lumiaggregometry for research and clinical laboratories. AB - Platelet aggregometry is often used to help diagnose storage pool disease (SPD reduced amounts of granule nucleotides) and release defects (abnormal release of granule nucleotides). The general assumption that normal aggregation patterns are sufficient to rule out the diagnosis of one of these disorders has been invalidated by the recent publication of two papers describing patients with clinical bleeding, prolonged bleeding times and normal aggregation patterns in spite of defective release. The lumiaggregometer provides a tool for measuring platelet release and aggregation simultaneously. This paper presents a standardized, reproducible method for the use of the lumiaggregometer based on a "standard curve". Data obtained during the development of the procedure are presented including normal ranges of release at different concentrations of agonists, release measured in intrinsic disorders as well as in patients on aspirin, and values for release relative to varying platelet counts. A monoclonal antibody (anti-p24/CD9; MAb7) which activates platelets similarly to thrombin and may be a useful reagent for distinguishing SPD and release defects is also introduced. PMID- 1519218 TI - Effects of injected antibody against the platelet glycoprotein IIb/IIIa complex on monkey platelet fibrinogen. AB - Four monkeys were injected for a 10-day period with the Fab fragment of a murine monoclonal antibody (NNKY 1-32) which inhibits the binding of fibrinogen to the platelet glycoprotein (GP) IIb/IIIa complex. Platelet fibrinogen levels were assessed quantitatively by electroimmunoassay and qualitatively by immunoelectron microscopy. The platelet fibrinogen level fell to 9.0 +/- 2.8% of the control level after antibody administration. Immunoelectron microscopy showed that the injected antibody was localized on the inner surface of the platelet alpha granule membrane. Our findings suggest that the GP IIb/IIIa complex can be internalized by alpha-granules and that it may mediate the endocytosis of plasma fibrinogen by platelets. PMID- 1519219 TI - Histidine-rich glycoprotein (HRG) in uncomplicated pregnancy and mild and moderate preeclampsia. PMID- 1519220 TI - Successful use of the APTT in monitoring of the anti-factor Xa activity of the heparinoid organon 10172 in a case of HITS requiring open heart surgery. PMID- 1519221 TI - The effect of instrumentation on thromboplastin calibration. PMID- 1519222 TI - Thrombosis in subjects with homozygous and heterozygous factor XII deficiency. PMID- 1519223 TI - Characterization of the phosphorylated state of protein 4.2 from a patient partially deficient in protein 4.2. AB - These studies compare the protein 4.2 found in a patient with osmotically fragile, spherocytic erythrocytes to the normal protein 4.2. The patient protein 4.2 is present in the erythrocyte ghost membranes as a doublet of 74 and 72 KDa at a concentration less than 1% of normal. The patient protein 4.2 becomes highly phosphorylated in the presence of Zn++ and is phosphorylated, relative to the amount of protein present, to a greater extent than the normal 72 KDa protein 4.2. These studies indicate that both the patient and the normal protein 4.2 usually exists in a highly phosphorylated state. The phosphorylation sites on the patient protein 4.2 appear to be more readily cycled than on the normal protein 4.2. Staphylococcus aureus V8 protease generates similar phosphopeptides in both the normal and patient protein 4.2 except for an extra 11 KDa phosphopeptide generated from the 74 KDa form of the protein. PMID- 1519224 TI - Zinc ions and alkaline pH alter the phosphorylated state of proteins 3 and 4.2 in human erythrocyte membranes. AB - The phosphorylation patterns of isolated red blood cell (RBC) membranes labeled with [gamma-32P] ATP are altered by Zn++ ions. Zn++ ions caused an increased phosphate incorporation into a 72 KDa protein and several proteins in the 40-60 KDa region and a decrease in the labeling of a 53 KDa protein. The 72 KDa and 53 KDa proteins have been identified as protein 4.2 and a protease-cleaved fragment of protein 3, respectively. Evidence suggests that the changes in phosphorylation pattern may be due to the stimulation of endogenous membrane alkaline phosphatase(s). Our results suggest that Zn++, at physiological concentrations in the intact erythrocyte, could modulate the phosphorylation of selected proteins which may regulate their association in the cytoskeletal network. PMID- 1519225 TI - Effect of heparin on in vitro platelet reactivity in cardiac surgical patients--a comparative assessment by whole blood platelet aggregometry and haemostatometry. AB - The in vitro effect of heparin on platelet reactivity was assessed simultaneously by haemostatometry (response to shear stress) and whole blood platelet aggregometry response to collagen (WBPA). From each blood sample a ratio (HR for haemostatometry and MR and IR for WBPA) showing platelet reactivity in the presence or absence of heparin (5 U/ml) was calculated. A value less than 1 represented a proaggregatory effect and greater than 1 an inhibitory effect. Non anticoagulated blood samples obtained from 290 cardiac surgical patients were tested by haemostatometry and citrated whole blood samples from 100 patients with aggregometry. Haemostatometry demonstrated a proaggregatory effect of heparin in 8.6% (25) and an inhibitory effect in 91.4% (265). Assessed by WBPA, heparin was proaggregatory in 41-46% and inhibitory in 54-59%. In the 100 patients tested by both methods there was a significant correlation between the findings with the two techniques (r = 0.46, p less than 0.0001). A wide individual variation in the platelet effect of heparin was demonstrated. This variation appeared greater and a higher proportion showed inhibition when blood was tested by haemostatometry. PMID- 1519226 TI - The in vivo effect in humans of pyridoxal-5'-phosphate on platelet function and blood coagulation. AB - Vitamin B6 has an antithrombotic effect. This, based on the results of in vitro studies, has been attributed to an antiplatelet effect. We assessed the in vivo effect of vitamin B6 by measuring the effect of long-term administration of vitamin B6 on platelet function and blood coagulation. Vitamin B6 (pyridoxine hydrochloride), 100mg twice daily p.o. for fifteen days, was administered to 10 healthy volunteers. The bleeding time was measured before the first dose and 15 days after. A baseline value, the acute effect, chronic effect, and the acute-on chronic effect of vitamin B6 was estimated by measuring platelet function. The following tests were performed: platelet aggregation induced by collagen, ADP and epinephrine; thromboxane A2 (TxA2)-production and prostacyclin inhibition of ADP induced aggregation. The effects on the coagulation system were monitored by measuring: the prothrombin time, activated partial thromboplastin time and levels of coagulation factor. Vitamin B6 significantly prolonged the bleeding time from 4.1 +/- 1.1 minutes to 6.8 +/- 1.0 minutes (p = 0.0063). Aggregation of platelets with collagen was slightly but not significantly inhibited. Platelet aggregation induced with the agonists ADP or epinephrine was significantly inhibited by vitamin B6, and the platelets tended to aggregate at a slightly decreased rate. The mean TxA2-production was slightly, but not significantly, decreased. Vitamin B6 had no effect on the sensitivity of platelets to prostacyclin, or on the coagulation system. Our results indicate that the antithrombotic effects of vitamin B6 is limited to inhibition of platelet function; there was no measurable influence on coagulation. The results of this in vivo study are however such that clinical trials are warranted to further assess the efficacy of vitamin B6 as an antiplatelet drug. PMID- 1519227 TI - Triflavin, an Arg-Gly-Asp containing snake venom peptide, inhibits aggregation of human platelets induced by human hepatoma cell line. AB - Triflavin, an Arg-Gly-Asp (RGD)-containing peptide, purified from snake venom of Trimeresurus flavoviridis, inhibits human platelet aggregation through the blockade of fibrinogen binding to fibrinogen receptors associated with glycoprotein IIb/IIIa complex. In this report, we examined the effect of triflavin on tumor cells (human hepatoma J-5)-induced platelet aggregation (TCIPA) of heparinized platelet-rich plasma (PRP). ADP-scavenger agents, apyrase (10 U/ml) and creatine phosphate (5 mM)/creatine phosphokinase (5 U/ml) did not inhibit TCIPA while hirudin (5 U/ml) completely inhibited it. J-5 cells initially induced platelet aggregation, then blood coagulation occurred. J-5 cells concentration-dependently shortened the recalcification time of normal as well as Factor VIII, IX-deficient human plasmas, while it was inactive at shortening the recalcification time of Factor VII-deficient plasma, suggesting J-5 cells induced platelet aggregation through activation of extrinsic pathway, leading to thrombin formation as evidenced by the amidolytic activity on s-2238 by expressing tissue factor-like activity. Triflavin inhibited TCIPA in a dose-dependent manner (IC50, 0.02 microM). When compared on molar ratio, triflavin was approximately 30,000 times more potent than GRGDS (IC50, 0.58 mM). On the other hand, GRGES showed no significant effect on TCIPA, even its concentration was raised to 4 mM. Additionally, the monoclonal antibodies, raised against glycoprotein IIb/IIIa complex (i.e., 7E3 and 10 E5) inhibited J-5 TCIPA. In conclusion, we suggest the inhibitory effect of triflavin on J-5 TCIPA may be chiefly mediated by the binding of triflavin to the fibrinogen receptor associated with glycoprotein IIb/IIIa complex on platelet surface membrane. PMID- 1519229 TI - Pharmacology of r-hirudin in renal impairment. AB - The pharmacokinetic properties of r-hirudin were studied in nine patients suffering from different degrees of renal insufficiency. To this end, r-hirudin was administered intravenously at dosages of 0.1 mg/kg. The elimination half-life t1/2 beta was determined in blood plasma and the cumulative r-hirudin excretion in urine was measured over 48 h. In healthy volunteers t1/2 beta was 0.9 +/- 0.2 h; the cumulative r-hirudin excretion in urine after 48 h amounted to 38 +/- 10% of the dose administered, most of this quantity was excreted during the first hours. In seven patients with chronic renal failure, t1/2 beta was 15 to 41 h; in three of these patients cumulative urinary r-hirudin excretion was increased to 70-80%, in four patients cumulative r-hirudin excretion in urine within 48 h amounted to 39 +/- 8%, but was delayed in time. In 2 bilaterally nephrectomized patients, t1/2 beta was 168 and 316 h, resp. The renal clearance of hirudin was significantly and linearly correlated with the creatinine clearance (r = 0.872). In all patients aPTT and bleeding time were only moderately prolonged. Because of the modified pharmacokinetic behaviour the administration of hirudin in patients with impaired renal function requires individually adjusted dosages or prolonged administration intervals. PMID- 1519228 TI - Comparative studies of drotaverine--acephyllinate (Depogen) and pentoxifylline (Trental). AB - Pentoxifylline is an orally active agent for the treatment of peripherial and cerebral vascular diseases. Pentoxifylline increases the deformability of red blood cells in vitro, reduces blood viscosity and decreases platelet aggregation and thrombus formation. Depogen has shown antiaggregatory effect both in vitro and in ex vivo. The inhibitory effect of Pentoxifylline was about 3-5 times weaker than that of Depogen. IC50 = 900/micrograms/ml for Depogen and 3600/micrograms/ml for Pentoxifylline on human platelet rich plasma. Depogen has shown ex vivo antiaggregatory effect on anesthetised rabbits, ID50 = 7 mg/kg in case of iv. administration, and ID50 = 300 mg/kg in case of orally administration. Both compound inhibit the release of platelet precoagulation factor, but the effect of Pentoxifylline was slighter. PMID- 1519230 TI - Direct evidence for systemic fibrinogenolysis in a patient with metastatic prostatic cancer. AB - Although the possible occurrence of systemic fibrinogenolysis has been suggested in patients with metastasising prostatic cancer (MPC), direct evidence is lacking. We report on a patient with MPC whose laboratory data were consistent with hyperfibrinolysis: marked decrease of alpha 2-antiplasmin (AP) level (less than 50% of normal), increase of plasmin-alpha 2-antiplasmin complex, D-fragment of fibrin and fibrinogen degradation products [FDP(D)] and cross-linked fibrin degradation products (XDP). The patient neither showed laboratory nor clinical evidence for consumption coagulopathy except for a slight increase in thrombin antithrombin III complex level. Immunoblotting of the patient's serum using an anti-fibrinogen antibody revealed the presence of a 250 kDa protein in addition to DD fragments. Following reduction of this protein by 2-mercaptoethanol after extraction from SDS-PAGE gel, gamma-chain of fibrinogen (47 kDa) was found by immunoblotting using a monoclonal antibody recognising a 86-302 residue of the gamma-remnant of fibrinogen. Moreover, the 250 kDa protein did not bind to Sepharose 4B to which a monoclonal antibody recognising the N-terminus of fragment D was conjugated. These findings indicated that this protein was not fragment DY, but rather fibrinogen fragment X. With the retraction of the prostatic tumour by an effective therapy, the patient's AP level increased gradually. When the plasma AP level rose to 60% of normal, the fragment X was no longer detectable. These findings suggested that systemic fibrinogenolysis occurred in the patient with MPC only when AP levels were markedly decreased. PMID- 1519231 TI - Recurrent venous thrombosis during warfarin treatment related to acquired protein S deficiency. AB - Failure of warfarin to prevent new thrombotic processes was observed in three patients with very low free protein S concentrations and high C4b-binding protein (C4bBP) concentrations, and in one patient with hereditary protein S deficiency. We suggest that an increase in C4bBP reduces the free Protein S level, and warfarin treatment causes an additional decrease of free protein S. The four patients presented indicate that such reductions are of clinical importance. Heparin seems preferable as an anticoagulant in this situation, as warfarin given alone is ineffective, or may even be harmful. In a group of pancreatic cancer patients with advanced disease, subnormal mean free protein S was found, whereas mean total protein S concentration, and mean C4bBP concentrations were significantly higher (p less than 0.01) than in healthy controls. These findings indicate that an increase in C4bBP may induce free protein S deficiency contributing to the increased thrombotic tendency in this group of patients. The correlation between free protein S and C4bBP was 0.11, (n.s.), between total protein S and C4bBP 0.73 (p less than 0.0001). PMID- 1519232 TI - Laboratory monitoring of thromboprophylaxis with low molecular weight and standard heparin. AB - This study was made to evaluate assays for monitoring of low dose heparin thromboprophylaxis and to evaluate its efficacy in reduction of hypercoagulation. Patients with medical diseases scheduled for routine thromboprophylaxis were subcutaneously treated with either 5.000 anti XaU low molecular weight (LMW) heparin once daily (n = 20) or 5.000 IU standard (ST) heparin 3 times daily (n = 19). On days 1,2,3, before, 1 and 4 hours after heparin injection APTT, TCT, anti Xa, Heptest, thrombin-antithrombin complexes (TAT), and D-Dimer levels were measured. In the LMW heparin group, median values of APTT and TCT slightly increased after heparin and the ranges of pre- and postinjection values showed extensive overlap. However, values of anti Xa and Heptest markedly increased, showing complete separation of ranges. In the ST heparin group neither APTT, TCT, anti Xa, nor Heptest were significantly different comparing pre- and postheparin values. Half of the patients in both groups had subclinical hypercoagulation at baseline (TAT greater than 5 ng/ml, D-Dimer greater than 200 ng/ml). On day 3 of prophylaxis this percentage was not significantly decreased. Moreover, several patients in both groups increased in TAT and D-Dimer. In the LMWheparin group, negative correlations between body weight and 4 h postinjection heparin levels were found (anti Xa R = -0.50, Heptest R = -0.31) and between 1 h postinjection heparin and TAT and D-Dimer levels 3 h later (TAT-anti Xa R = -0.58, TAT-Heptest R = -0.64, D-Dimer-anti Xa R = -0.32, D-Dimer-Heptest R = -0.33).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1519233 TI - Replacement of m-calpain by mu-calpain during maturation of megakaryocytes and possible involvement in platelet formation. AB - Localization of calpains in human bone marrow cells was studied immunohistochemically employing monoclonal antibodies against the high-Ca(2+) requiring form (m-calpain) and the low-Ca(2+)-requiring form (mu-calpain). Most cells were stained with anti-m-calpain more strongly than with anti-mu-calpain, and staining with anti-mu-calpain was prominent only in megakaryocytes. To confirm the result, megakaryoblastic cell line (T-33) cells were subjected to immunoblot analysis. However no immunoreactivity to mu-calpain was seen in T-33 cells. Bone marrow from a patient with idiopathic thrombocytopenic purpura showed immature megakaryocytes (stage II) strongly stained by anti-m-calpain antibody while mature cells (stage III) were strongly stained by anti-mu-calpain antibody. These results suggest that mu-calpain plays a crucial role in mature megakaryocytes, possibly in platelet production. PMID- 1519234 TI - Blood serotonergic mechanisms in type 2 (non-insulin-dependent) diabetes mellitus. AB - Serotonin (5-hydroxytryptamine, 5HT) is believed to play a role in vasospasm and increased platelet aggregability that in turn could contribute to atherosclerosis. The present study was designed to evaluate a possible participation of serotonin in the development of vascular complications in diabetes mellitus. Whole blood and plasma serotonin, the platelet uptake and release of the amine and serotonin- induced platelet aggregation were studied in 32 patients with Type 2 diabetes. The patients were divided into three groups according to the presence and advancement of retinopathy. Mean levels of blood serotonin content were significantly lower in diabetic patients. The concentration of the amine in the plasma was markedly increased in diabetes. It was correlated with vascular changes of the retina. We established that platelets from diabetic patients took up less serotonin when compared to the control group. Concomitantly enhanced spontaneous release of 5HT from platelets was observed. The platelets of diabetic patients showed increased response to serotonin. There was a relation between serotonin-induced aggregation and the presence of retinopathy. These results suggest that serotonin may be involved in the pathogenesis of diabetic vasculopathy. PMID- 1519235 TI - Determination of thrombin-antithrombin-III-complex is not a suitable screening test for detecting deficiency of protein C or protein S. PMID- 1519236 TI - Acute t-PA release by defibrotide. PMID- 1519237 TI - Some hemostatic and hemorheological disorders in auditory and vestibular impairments. PMID- 1519238 TI - Behavioural effects of neonatal metallic mercury exposure in rats. AB - The effect of neonatal exposure of rats to mercury vapour (Hg0), at the concentration 0.05 mg/m3, 1 h (low dose) or 4 h (high dose), on the behaviour in adulthood were studied. Exposure occurred on days 11-17 (the period of rapid brain growth). Tests for spontaneous motor activity were performed at the ages of 2 and 4 months. Rats exposed to the high dose Hg0 showed a marked increase in variables locomotion and total activity but a decrease for rearing when tested at 2 months of age. At 4 months of age these rats showed a marked hypoactivity with respect to all three variables. Rats exposed to the low dose showed no significant differences at 2 months compared to controls. However, at the age of 4 months the same pattern (increase in variables locomotion and total activity but a decrease for rearing) already noticed in the high dose group at 2 months was observed. In the spatial learning tasks applied, the radial arm maze and circular swim maze, neonatally exposed pups showed a retarded acquisition to the former, while there was no difference compared to controls in the latter. These data indicate that neonatal exposure to mercury vapour results in similar behaviour changes as reported from offspring prenatally exposed to mercury vapour or methylmercury. Furthermore, exposure for 1 week to concentrations around Swedish threshold values (TLV) for 1 or 4 h resulted in dose and age-related behavioural changes. PMID- 1519239 TI - Investigation of the role of estrogenic action and prostaglandin E2 in DDT stimulated rat uterine contractions ex vivo. AB - Previous work in our laboratory showed that o,p'-DDT increases the frequency of rat uterine contractions in vitro. The present study investigated whether this response was related to prostaglandin E2 (PGE2) release from the uterine strips or to the estrogenicity of o,p'-DDT. Contraction frequency was evaluated by recording isometric spontaneous contractions in longitudinal uterine strips from pregnant rats. Assessment of PGE2 levels in the muscle bath showed no significant differences between control and DDT-treated strips, although significant amounts of PGE2 were detected in both groups and increased contraction frequency was observed in o,p'-DDT-treated strips. Furthermore, a role for direct estrogenic action in the medication of o,p'-DDT-stimulated uterine contraction was not supported by the contractility data, because: (i) unlike o,p'-DDT, 17-beta estradiol had no stimulatory effect, but instead exerted a significant inhibitory effect on uterine contraction; (ii) the estrogen antagonist, tamoxifen, failed to block the stimulatory effect of o,p'-DDT; and (iii) p,p'-DDD, a non-estrogenic DDT analogue, significantly stimulated contraction frequency, similar to o,p' DDT. These results suggest that the stimulatory effect of o,p'-DDT on contraction frequency is not dependent on PGE2 release or direct estrogen receptor-related action. PMID- 1519240 TI - Combined exposure to NO2, O3 and H2SO4-aerosol and lung tumor formation in rats. AB - The promoting effects of a combined exposure to two pollutants (NO2, O3 or H2SO4 aerosol) at near ambient levels on lung tumorigenesis induced by N-bis(2 hydroxypropyl) nitrosamine (BHPN) were investigated in male Wistar rats. The rats were given a single intraperitoneal injection of BHPN (0.5 g per kg body wt.) at 6 weeks of age. They then were exposed to clean air, 0.05 ppm O3 (mean concentration for 10 h/day; 0.1 ppm peak concentration), 0.05 ppm O3 (mean concentration for 10 h/day; 0.1 ppm peak concentration) + 0.4 ppm NO2 or 0.4 ppm NO2 + 1 mg/m3 of H2SO4-aerosol for 13 months and were then maintained in a clean room for another 11 months. Room control animals were kept after injection of BHPN in a clean room for 24 months. The incidence of primary lung tumors in rats exposed to 0.05 ppm O3, 0.05 ppm O3 + 0.4 ppm NO2 and 0.4 ppm NO2 + 1 mg/m3 of H2SO4-aerosol with BHPN treatment was 8.3% (3 out of 36 rats), 13.9% (5 out of 36 rats) and 8.3% (3 out of 36 rats), respectively. The tumors were adenomas and adenocarcinomas. The incidence of adenomas was 2.8% (1 out of 36 rats) in the O3 alone group, 11% (4 out of 36 rats) in O3 + NO2 group and 5.6% (2 out of 36 rats) in NO2 + H2SO4 group. The incidence of adenocarcinomas was 5.6% (2 out of 36 rats) in the O3 group, 2.8% (1 out of 36 rats) in O3 + NO2 group and 2.8% (1 out of 36 rats) in NO2 + H2SO4 group. No lung tumors were found in the rats exposed to clean air with BHPN treatment and in animals not given BHPN but exposed to each air pollutant. The difference in tumor incidence between the clean air group with BHPN and the O3 + NO2 group with BHPN was statistically significant. The results show that exposure to O3 alone enhances tumor development and that the combined exposure to O3 or H2SO4 with NO2 produces an additional increase in incidence of lung tumor, respectively. The incidence of slight-moderate to marked alveolar cell hyperplasia in the groups exposed to each air pollutant with BHPN treatment was higher than that in the groups exposed to clean air with BHPN. Exposure to each air pollutant had no effect on the development of bronchiolar mucosal hyperplasia in lungs of rats treated with BHPN.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1519241 TI - Effect of ICRF-187 on the pulmonary damage induced by hyperoxia in the rat. AB - Histological and ultrastructural studies were made of the lungs of rats that were exposed to 100% oxygen for 60 h and were treated with either normal saline or with ICRF-187, a bis-diketopiperazine derivative of EDTA that has the capacity to chelate iron. This metal is thought to be needed to catalyze the formation of toxic oxygen free radicals. ICRF-187 (20 mg/kg) was given intraperitoneally at approximately 12 h intervals (5 doses) during the 60 h exposure. Seven of the ten saline-treated rats exposed to oxygen died prior to the end of the study whereas only one of the 10 rats in the ICRF-187-treated group died. This difference in mortality is found to be statistically significant (P less than 0.05). All saline treated rats showed light and electron microscopic evidence of pulmonary damage. ICRF-187 attenuated the morphologic alterations observed by light microscopy (intra-alveolar edema, inflammatory exudates and bronchiolar epithelial cell swelling and hyperplasia; P less than 0.05). In addition, electron microscopic evaluation revealed that capillary thrombi, endothelial cell alterations and alveolar epithelial cell damage also were less severe in ICRF-187-treated rats. It is concluded that ICRF-187 may provide a new and useful approach for the prevention of hyperoxia-induced pulmonary damage. PMID- 1519242 TI - Late postnatal growth in the dentate area of the rat hippocampus compensates for volumetric changes caused by early postnatal toluene exposure. AB - The present report assesses the reversibility of previously described quantitative morphological alterations in the dentate area of the hippocampi of rats exposed to 500 ppm toluene for 12 h daily from postnatal day 1 (P1) to P28. Following the exposure, rats were allowed to survive until P120. The volumes of hippocampal components, as they appear in Timm-stained histological sections, were determined using the Cavalieri estimator. At P120, no differences were apparent in the volumes of the dentate components of control and experimental animals. The differences observed immediately after exposure were eliminated by significantly larger increases in the sizes of early affected components in experimental animals. Different periods of neurogenesis in rodents and primates are briefly discussed as possible confounders of rodent models of permanent toluene-induced morphological alterations in primates. PMID- 1519243 TI - Dietary glucarate-mediated inhibition of initiation of diethylnitrosamine-induced hepatocarcinogenesis. AB - Previously, it has been reported that calcium glucarate is a potent inhibitor of chemical carcinogenesis, including phenobarbital-promoted diethylnitrosamine initiated hepatic toxicity expressed as altered hepatic foci in rats. The purpose of the present study was to determine whether calcium glucarate could inhibit the immediate and delayed appearance of altered hepatic foci when fed to rats during the initiation phase of diethylnitrosamine-induced hepatocarcinogenesis. The effects of dietary mode of administration of calcium glucarate on the initiation phase of hepatocarcinogenesis were also examined. Since diethylnitrosamine is not known to undergo glucuronidation and calcium glucarate has been shown to enhance clearance of circulating estrogens, an indirect mechanism of action of calcium glucarate was also evaluated by pretreating rats with an anti-estrogen, tamoxifen, prior to partial hepatectomy and administration of diethylnitrosamine. Calcium glucarate significantly inhibited both the early and delayed appearance of altered hepatic foci and exerted maximal inhibition when administered by gavage prior to diethylnitrosamine. Maximal inhibition was obtained when calcium glucarate was provided continuously in the diet of animals up to 5 and 7 months. Pretreatment of animals with tamoxifen before partial hepatectomy and diethylnitrosamine resulted in maximal inhibition of the initiation phase of hepatocarcinogenesis. This suggests but does not prove that the anti-carcinogenic activity of calcium glucarate was due to decreased liver proliferation. In the present study, the proliferation of ductular epithelial and oval cells appeared to be associated with the administration of diethylnitrosamine. Collectively, our data suggest that calcium glucarate inhibited the initiation phase of diethylnitrosamine-induced hepatocarcinogenesis. PMID- 1519244 TI - Benznidazole-induced ultrastructural alterations in rat adrenal cortex. Mechanistic studies. AB - Benznidazole (Bz) (N-benzyl-2-nitro-1-imidazole acetamide) is a drug used against Chagas' disease, a parasitic disease afflicting several millions of Latin Americans. Bz administration to Sprague-Dawley male rats at 100 mg/kg p.o. caused subcellular alterations in the adrenal cortex involving fasciculata and reticularis zones but not in the glomerulosa. There is Bz nitroreductase activity in the adrenal microsomal and mitochondrial fractions but most of it is localized in mitochondria. Activity in the two fractions requires NADPH under anaerobic conditions. Mitochondrial Bz nitroreductase activity was inhibited by oxygen. A minor but statistically significant inhibition was observed in mixtures incubated under carbon monoxide. Microsomal Bz nitroreductase activity was not detected under oxygen atmosphere and was not inhibited under carbon monoxide. No Bz nitroreductase activity mediated by xanthine oxidase or aldehyde oxidase was detected in the cytosolic fraction from rat adrenals. Electron microscopic examination of the adrenal cortex from Bz-treated animals revealed cells with marked lipid accumulation and alterations in nuclei, endoplasmic reticulum and mitochondria in the reticularis and fasciculata zones. In vitro results suggest a Bz nitroreductive activation, with minor or null P-450 participation, leading to reactive metabolites able to cause damage in various organelles. PMID- 1519245 TI - The toxicokinetics of mercury in mice offspring after maternal exposure to methylmercury--effect of selenomethionine. AB - Human evidence indicates fetotoxicity of methylmercury at exposure levels inducing only slight and reversible maternal toxicity, but experimental animal data demonstrate, that fetotoxicity may occur despite absence of noticeable maternal toxicity. However, in contrast to the long-term exposure in humans, the key point in the experimental design of the majority of experimental studies has been administration of few doses of methylmercury late in gestation. The present study in mice therefore used long-term maternal exposure to methylmercury (1 nmol/ml in drinking water) and a cross-fostering design to investigate separately in different offsprings the toxicokinetics of transplacentally absorbed mercury and mercury retained during lactation. Further, the influence of seleno-L methionine (3 micrograms/ml in drinking water) on the toxicokinetics of methylmercury in these mice was studied. The present study demonstrated, that independent on seleno-L-methionine supplementation, offspring deposited equal amounts of mercury during lactation and during gestation. Moreover, the organ distribution and rate of excretion of mercury in transplacentally exposed mice were considerably different from those in mice exposed postnatally and from adult mice in studies using comparable dosages. Seleno-L-methionine only slightly affected the toxicokinetics of mercury in offspring. PMID- 1519246 TI - Proliferative responses of quail aortic smooth muscle cells to benzo[a]pyrene: implications in PAH-induced atherogenesis. AB - Repeated exposure of avian and rodent species to benzo(a)pyrene (BaP) has been associated with the development of aortic lesions of atherosclerotic etiology. Because the occurrence of these lesions may involve alterations in the regulation of smooth muscle cell (SMC) growth, the present studies were conducted to evaluate the proliferative responses of quail aortic SMCs to BaP treatment in vivo and in vitro. Measurements of [3H]thymidine incorporation and cell growth were conducted in cultured aortic SMCs isolated from male Japanese quail treated with 10 mg/kg BaP or vehicle weekly for 10 weeks or in naive aortic SMCs exposed in vitro to BaP (0.003-30 microM). Inhibition of DNA synthesis was observed in primary and early passage cultures of aortic SMCs isolated from BaP-treated quail relative to controls. Continued propagation of these cultures yielded a population of BaP cells which proliferated at faster rates than controls. The proliferative phenotype induced by BaP was first observed after the tenth passage and preserved in all subsequent passages tested. In vitro growth of SMCs from BaP treated animals was serum- and anchorage-dependent. A 24-h exposure of cycling SMC cultures to BaP (0.003-30 microM) was associated with a dose-dependent decrease in DNA synthesis and significant delay in the progression of SMCs through the cell cycle. A time-course study revealed that maximal inhibition of DNA synthesis occurred 10 h after addition of 3 microM BaP to cycling cultures of SMCs. As seen in SMCs isolated from BaP-treated quail, serial subculture of SMCs exposed to 0.3 microM BaP in vitro for 24 h yielded a fast-growing population of cells. In these cultures, expression of the proliferative phenotype was observed after the fifth passage. These data suggest that BaP induces the expression of a proliferative phenotype in aortic SMCs characterized by enhanced serum responsiveness. This phenotypic modulation may contribute to the initiation and/or progression of vascular lesions of atherosclerotic etiology induced by BaP. PMID- 1519247 TI - A review of the literature on potential reproductive and developmental toxicity of electric and magnetic fields. AB - The potential of electric and magnetic fields to adversely affect the health of the human population is an issue which continues to receive a great deal of attention in both public and scientific forums. One of the critical issues is the possibility that such fields may adversely affect the reproductive process. Numerous studies investigating the potential of electric and/or magnetic fields to alter reproduction in vertebrates have been conducted. These studies have, in many instances, yielded seemingly contradictory results. A number of epidemiological studies have been conducted as well. This review of the literature examines relevant studies and attempts to draw biologically rational conclusions from them. The studies are ordered in broad categories based upon both classification of the species studied (i.e. submammalian, mammalian exclusive of man and human) and the agent used (i.e. extremely low frequency electric, very low frequency electric, and magnetic fields). From our review we conclude that laboratory experimental and epidemiological results to date have not yielded conclusive data to support the contention that such fields induce adverse reproductive effects under the test or environmental conditions studied. Additional studies may, however, be warranted to clarify some of the experimental results obtained. PMID- 1519248 TI - Text of the Redi Award presented to Prof. Dr. Ernest Richard Habermann. In recognition of an outstanding career in the field of toxicology. PMID- 1519249 TI - Pioneers of anti-venomous serotherapy: Dr Vital Brazil (1865-1950). AB - Dr Vital Brazil was a great humanitarian and pioneer of medical science. His main work arose from his concern with poisonous snakebite accidents to labourers working the land. Vital Brazil estimated that, at the beginning of this century, deaths due to crotaline snakebites in the State of Sao Paulo, Brazil, were nearly 3000 per year, representing a mortality rate of about 25%, the majority being due to bothropic envenomation. After reading a report of Calmette's anti-Naja serum, Vital Brazil raised monovalent serum against the venom of Bothrops jararaca and the venom of Crotalus durissus terrificus. In 1989 this led to the first demonstration of the specificity of anti-venomous serum and later, the first production of polyvalent serum for therapeutic use. As Director of the newly founded Institute Butantan in Sao Paulo, Vital Brazil was actively engaged in every aspect of serotherapeutic treatment. This included organizing a unique system of exchanging anti-ophidic serum for snakes as well as a wide-ranging teaching programme. His many outstanding contributions to the fields of immunology, public health, toxinology and herpetology required not only a very high level of observational, deductive and practical ability but also an unswerving vision and sense of duty; this was allied to great administrative skill and exceptional energy. PMID- 1519250 TI - Inhibition of the proteolytic activity of hemorrhagin-e from Crotalus atrox venom by antihemorrhagins from homologous serum. AB - Antihemorrhagic proteins from Crotalus atrox serum were tested for their ability to inhibit the proteolytic activity of the hemorrhagic toxin-e from Crotalus atrox venom and of several other proteolytic enzymes: trypsin, collagenase and thermolysin. The antihemorrhagic proteins inhibited the proteolytic activity of hemorrhagin-e when tested on gelatin type I and collagen type IV, the proteolytic activity of trypsin on photofilm gelatin and the proteolytic activity of whole venom when tested on azocollagen and photofilm gelatin. The antihemorrhagins failed to inhibit the proteolytic activity of trypsin when tested on the specific synthetic substrate N-acetyl-DL-phenylalanine-beta-naphthyl ester (APNE), the activity of microbial collagenase on N-(3-[2-furyl]acryloyl)-Leu-Gly-Pro-Ala (FALGPA) or on azocollagen and the activity of thermolysin on N-(3-[2 furyl]acryloyl)-Gly-Leu amide (FAGLA). It is tentatively suggested that the antihemorrhagins from snake blood serum are proteinase inhibitors that underwent specialization towards the neutralization of the proteolytic activity of hemorrhagic toxins. PMID- 1519251 TI - Envenoming by viper bites in France: clinical gradation and biological quantification by ELISA. AB - Viper bites are frequent in France but the evaluation of the severity of envenomings and consequently patient treatment has not yet been properly evaluated. The purpose of this study was to measure venom antigens in blood and/or urine of bitten patients and to establish a quantitative relationship with clinical observations. A prospective enquiry was conducted in 1990 in France to collect epidemiological, clinical and biological data from hospitals. Urine and blood samples were tested for their content of Vipera aspis venom antigens by a sandwich enzyme linked immunosorbent assay (ELISA). One hundred and two charts were analysed, from patients presenting documented viper bites. Oedema was the prominent local feature (81 cases). Systemic signs consisted of vomiting and/or diarrhoea (22 cases), slight or severe hypotension (15 cases), shock (2 cases) and bleeding (1 case). A relationship was observed between these systemic signs and the extent of the oedema, which permitted the establishment of a grading scale. Grade 0 (no envenoming) was identified by fang marks and absence of oedema and local reaction; grade 1 (mild envenoming) by local oedema and absence of systemic symptoms; grade 2 (moderate envenoming) by regional oedema and moderate systemic symptoms; and grade 3 (severe envenoming) by extensive oedema and severe systemic symptoms. Quantification of venom antigens in blood or urine of patients by ELISA revealed a significant correlation between clinical signs of envenoming and the level of venom antigens in blood or urine. This indicated that the ELISA test is a useful and predictive tool for clinically grading viper envenomings. PMID- 1519252 TI - [Pharmacologic and enzymatic effects of snake venoms from Antioquia and Choco (Colombia)]. AB - We compared several pharmacological and enzymatic effects induced by 11 snake venoms from seven species, six of them from different geographic areas of Antioquia and Choco, north-west of Colombia, South America (Bothrops atrox, B. nasutus, B. schlegelii, B. punctatus, Lachesis muta, Micrurus mipartitus), and Crotalus durissus terrificus venom, from specimens captured in other provinces of the country (Tolima, Huila, Meta and Atlantico). Differences were observed in edema-forming, hemorrhage, defibrination, indirect hemolysis, myonecrosis, proteolysis and lethal activity between venoms from different genera or species, as well as according to the geographic area of origin in B. atrox and B. nasutus snake venoms. Bothrops venoms, in particular B. atrox and L. muta, produced major local effects. All of the venoms, including M. mipartitus, had myotoxic effects. The most defibrinating venoms were B. atrox, L. muta, B. punctatus and C. d. terrificus. All of the venoms had indirect hemolytic activity; the venom of M. mipartitus being greatest. The most lethal venoms were those of C. d. terrificus and M. mipartitus. Within Bothrops species, the venom of B. schlegelii was the least active in terms of local and systemic pathologic effects. PMID- 1519253 TI - Specificity of action of beta-bungarotoxin on acetylcholine release from synaptosomes. AB - Presynaptically acting phospholipase A2 (PLA2) neurotoxins such as beta bungarotoxin (beta-BuTX) specifically modify the release of acetylcholine (ACh) in the periphery, whereas in the central nervous system (CNS) the release of other neurotransmitters such as norepinephrine (NE) and serotonin (5-HT) are also modified. In addition, ACh release in the periphery is modified in a triphasic manner (decrease, then increase, then block), while in the CNS only the increase has been demonstrated. To determine the specificity of the central effects of beta-BuTX we compared the effects of beta-BuTX and N. n. atra PLA2 on the release from rat cerebrocortical synaptosomes of ACh, NE, and 5-HT. We also measured the leakage of lactate dehydrogenase (LDH) in order to determine whether membrane permeablization was responsible for neurotransmitter leakage. Both the PLA2 neurotoxin (5.0 nM) and the non-neurotoxic enzyme (0.5 nM) stimulated the loss of NE and 5-HT, but only at concentrations which induced leakage of LDH. Conversely, beta-BuTX stimulated the release of ACh at a concentration (0.5 nM) which caused no leakage of LDH, while N. n. atra PLA2 (0.5 nM) did not stimulate ACh release. beta-Bungarotoxin thus exerts a specific effect on cholinergic nerve terminals, while the leakage of NE and 5-HT induced by beta-BuTX and N. n. atra PLA2 correlates with membrane disruption due to their PLA2 activities. Within 20 min, 0.5 nM beta-BuTX increased the resting release of ACh and decreased the stimulated release induced by depolarization with 4-aminopyridine, while N. n. atra PLA2 (0.5 nM) did not stimulate ACh release and required 45 min to exert an inhibitory effect. beta-BuTX (5.0 nM) also exerted an inhibitory effect on ACh release stimulated by veratridine, but not by high KCl. It is concluded that in low concentrations that do not disrupt membrane permeability, beta-BuTX acts specifically on cholinergic terminals in rat synaptosomes, where it exerts both stimulatory and inhibitory effects. PMID- 1519254 TI - Isolation of immunogenic and lethal peptides of alpha-toxin from Clostridium novyi type B. AB - The lethal alpha-toxin was isolated from the culture filtrate of Clostridium novyi type B using ammonium sulfate precipitation and ion exchange chromatography. The alpha-toxin has a mol. wt of 190,000 and does not contain any disulfide cross-linkages. It consists of a single polypeptide chain. The peptide fragments resulting from the cyanogen-bromide cleavage were isolated using reversed phase and gel filtration HPLC. The immunogenic actions of these peptides and peptide mixtures were studied in Balb/c mice. Three polyclonal antisera recognizing the uncleaved native toxin could be found using an ELISA test (Br3, Bro2, Bro5). One peptide mixture (Tx5), which was proved lethal in shell-less quail eggs (in vitro), was rechromatographed with gel filtration HPLC that resulted in one peptide with mol. wt 3000 (Txleth), which again proved lethal in the shell-less quail egg lethality test. The immunogenic peptides differ from the lethal one, therefore we assumed different locations on the polypeptide chain. The separation of the immunogenic, non-toxic fragment from the lethal one may allow the production of a highly specific non-toxic vaccine. By using synthetically produced immunogenic peptides, time-consuming purification methods and working with the whole toxin will become unnecessary. PMID- 1519255 TI - Comparison of paralytic toxins in aquaculture of purple clam in Taiwan. AB - Food poisoning incidents due to ingesting the cultured purple clam Soletellina diphos occurred in western Taiwan in February 1991. Clam specimens, sediment and the dinoflagellate Alexandrium tamarensis were collected and assayed for lethality as paralytic shellfish poison (PSP). The lethality of purple clam, wet sediment and phytoplankton was 1700 mouse units per specimen (MU/specimen), 0.05 MU/g and 3.6 x 10(-5) MU/cell, respectively. The toxins obtained from clam, sediment and phytoplankton consisted of gonyautoxins 1-4, along with trace amounts of neosaxitoxin. PMID- 1519256 TI - Diarrhoeic shellfish toxins in Adriatic Sea mussels evaluated by an ELISA method. AB - A competitive enzyme immunoassay (ELISA) was used to determine the presence of okadaic acid (OA) and/or dinophysistoxin-1 (DTX-1) in mussels. The accuracy and sensitivity of the ELISA method has been checked. The sensitivity of the method (100 ng/g of hepatopancreas) makes it possible to determine OA concentrations ten times lower than the tolerance limits established by the Health Authorities of many countries. For the first time, OA and/or DTX-1 were detected in mussels (Mytilus galloprovincialis) collected in different stations along the Adriatic Sea coasts. PMID- 1519257 TI - Bibliography of toxinology. PMID- 1519258 TI - A sensitive enzyme-linked immunosorbent assay (ELISA) for testosterone: use of a novel heterologous hapten conjugated to penicillinase. AB - A microplate enzyme-linked immunosorbent assay (ELISA) has been developed for the measurement of testosterone in plasma. The assay uses a heterologous system consisting of a novel hapten 4-(17 beta-hydroxy-3-oxoestra-4,9-dien-11 beta yl)butanoic acid (1) conjugated to penicillinase (beta-lactamase). The key reaction in the synthesis of the hapten was the cuprate-mediated 1,4-conjugate addition on 3,3,17,17-bis-ethylenedioxy-5 alpha,10 alpha-oxido-estr-9(11)-ene by the Grignard reagent derived from trimethyl 4-bromoorthobutyrate; this regiospecifically introduces the 11 beta-butanoate function. The hapten penicillinase conjugate was used in the assay in conjunction with the immunoglobulin G (IgG) fraction derived from a previously characterized, highly specific, antitestosterone serum raised against a testosterone-19-O-carboxymethyl ether-bovine serum albumin (T-19-O-CME-BSA) conjugate. This unique system represents one incorporating three elements of structural heterology: bridge, site, and ring heterology between the antigen hapten and enzyme-linked hapten. The limit of detection was 10 pg of testosterone with a sensitivity range between 15 and 1,000 pg. A low level of cross-reactivity with 5 alpha-dihydrotestosterone (6.17%) and 11 beta-hydroxytestosterone (1.03%) was noted. No interference was noted with other common androgens, estradiol, or progesterone. The sensitivity and selectivity observed in the assay may be attributable to the selection of penicillinase as the enzyme marker and the elements of conformational heterology between the antigen-linked and enzyme-conjugated steroid haptens. PMID- 1519259 TI - Synthesis of 3 alpha, 7 alpha-dihydroxy-5 beta-cholestan-26-oic acid from 3 alpha,7 alpha,12 alpha-trihydroxy-5 beta-cholestan-26-oic acid: configuration in the bile of Alligator mississippiensis. AB - Synthesis of 25R- and 25S-diastereoisomers of 3 alpha,7 alpha-dihydroxy-5 beta cholestan-26-oic acid from 3 alpha,7 alpha,12 alpha-trihydroxy-5 beta-cholestan 26-oic acid is described. The 25S-diastereoisomer of 3 alpha,7 alpha,12 alpha trihydroxy-5 beta-cholestan- 26-oic acid was obtained by vigorous hydrolysis of the bile of Alligator mississippiensis followed by repeated crystallization of the hydrolysate, and the 25R-diastereoisomer was isolated by hydrolysis of the bile salts in bile of A mississippiensis with rat feces. Acetylation of the 25R- or 25S-diastereoisomer of methyl 3 alpha,7 alpha,12 alpha-trihydroxy-5 beta cholestan-26-oic acid under controlled conditions yielded the corresponding 3 alpha,7 alpha-diacetate in approximately 70% yield. The diacetate was quantitatively oxidized to methyl 3 alpha,7 alpha-diacetoxy-12-oxo-5 beta cholestan-26-oate, which was converted into the 12-tosylhydrazone in approximately 58% yield. Reduction of the tosylhydrazone with sodium borohydride in acetic acid yielded the 25R- or the 25S-diastereoisomer of 3 alpha,7 alpha dihydroxy-5 beta-cholestan-26-oic acid as the major product. Purification via column chromatography yielded the pure diastereoisomers in approximately 25% overall yield. The two diastereoisomers were resolved on thin-layer chromatography and high-performance liquid chromatography. When the bile of A mississippiensis was hydrolyzed with rat fecal bacteria, the 3 alpha,7 alpha dihydroxy-5 beta-cholestan-26-oic acid isolated via chromatographic purification was shown to be the 25R-diastereoisomer. PMID- 1519260 TI - The study of properties of immunoreactive estradiol secreted by adrenals and ovaries of immature female rats. AB - Some properties of immunoreactive estradiol secreted by adrenals and ovaries of immature female rats were studied. It was shown that adrenals and ovaries of 15 day-old animals secrete approximately equal amounts of immunoreactive estradiol, with thin-layer chromatogram of immunoreactive material being identical for both glands. Adrenal- as well as ovarian-derived estradiol can bind to uterine cytosol estradiol receptors with the formation of complexes, which can be activated in the cell-free system. The removal of either adrenals or ovaries causes a decrease of cytosol estradiol receptor levels in the uterus 6 hours after the operation. From these results and previously reported data, nothing suggests that immunoreactive estradiol secreted by the adrenals of immature rats should be regarded as "spurious" hormone. PMID- 1519261 TI - Enzyme immunoassay for serum dexamethasone using 4 (carboxymethylthio)dexamethasone as a new hapten. AB - A sensitive and simple enzyme immunoassay for direct quantitation of serum dexamethasone was established. An antiserum with high specificity was produced by the immunization of rabbits with a newly synthesized 4 (carboxymethylthio)dexamethasone-bovine serum albumin conjugate. Alkaline phosphatase was used as a labeling enzyme. The minimum amount of dexamethasone detected was 2 pg per tube on the basis of B/Bo 100 - 2 SD (%) of standard curve. However, taking into account the cross-reaction with steroids such as cortisol in dexamethasone-free serum, the measurable range was from approximately 0.13 to 10 micrograms/dl. Intra- and interassay coefficients of variation were 1.5 - 5.4% and 0.6 - 6.5%, respectively. Serum levels of dexamethasone and cortisol in four normal subjects after an oral administration of 1 mg of dexamethasone are also reported. PMID- 1519262 TI - Tyrosinase-like polypeptides in the uterus and in the central nervous system of rats. AB - Nuclear and cytosolic fractions of rat uteri and tissues from the central nervous system contain proteins that are recognized by a polyclonal tyrosinase antibody. This antibody eliminates the cresolase activity of uterine nuclear extract when estradiol is used as substrate. Thus, it appears that tyrosinase-like proteins might be present in tissues not generally considered to chain such an enzyme. PMID- 1519263 TI - Synthesis of sulfonate analogs of bile acids. AB - Sulfonate analogs of C23 and C24 bile acids were synthesized from norcholic, norchenodeoxycholic, norursodeoxycholic, nordeoxycholic, norhyodeoxycholic, cholic, deoxycholic, hyodeoxycholic, and lithocholic acids. The principal reactions used were (1) reduction of the bile acids with NaBH4 to the corresponding bile alcohols, (2) selective tosylation of the terminal hydroxyl group, (3) iodination of the tosyl esters with NaI, and (4) treatment of the iodides with Na2SO3 to form the sulfonate analogs of the bile acids. The sulfonate analogs showed polarity similar to that of taurine-conjugated bile acids on thin-layer chromatography. The carbon 13 nuclear magnetic resonance spectral data for the sulfonate analogs were tabulated. PMID- 1519264 TI - Synthesis and evaluation for uterotrophic and antiimplantation activities of 2 substituted estradiol derivatives. AB - Two novel series of 2-substituted estradiol derivatives have been synthesized and evaluated for uterotrophic and antiimplantation activities. Among the compounds tested in the rat, 2-acetylestradiol 17 beta-acetate (1), 2-(3'-dimethylamino-1' propionyl)estradiol 3,17 beta-diacetate (7), 2-(3'-diethylamino-1' propionyl)estradiol 3,17 beta-diacetate (8), 2-(3'-piperidino-1' propionyl)estradiol 3,17 beta-diacetate (9), 1'-(2-estradiol 3,17 beta-diacetate 3'-diethylaminopropionyl thiosemicarbazone (12), and 1'-(2-estradiol 3,17 beta diacetate)-3'-morpholinopropionyl thiosemicarbazone (14) displayed estrogenic activity. At dosages of 4 microliters/rat/day, none of the tested compounds elicited antiimplantation activity. All compounds shared a similar characteristic: nuclear substitution at the C-2 position of the steroid nucleus, a property previously thought to be markedly inhibitory for estrogenic activity. PMID- 1519265 TI - Synthesis of 6 alpha-tritiated beta-muricholic acid for use as a molecular probe. AB - Regioselective oxidation of methyl beta-muricholate to give the 6-ketoderivative is described. Stereoselective reduction of this ketone with tritiated NaBH4 furnishes labeled methyl beta-muricholate. The structure of all compounds was confirmed by infrared, 1H, and 13C nuclear magnetic resonance spectroscopy. Data obtained by circular dichroism and mass spectroscopy were in agreement with the structure of the ketone 3. PMID- 1519266 TI - Early English steroid history. AB - Following the revelation of the presence of vitamin D in fish liver oils and of estrogenic hormones in pregnancy urine in the 1920s, active interest in the steroids began in England. Most of this interest originated from the studies of Ian Heilbron at Liverpool and of Otto Rosenheim at the National Institute for Medical Research in London. PMID- 1519267 TI - Steroid hormones and the Luftwaffe. A venture into fundamental strategic research and some of its consequences: the Birch reduction becomes a birth reduction. AB - I recount my involvement in the development of biologically active, totally synthetic steroid hormones since 1941. The reasons for my approach to the first total synthesis of a potent androgen are given. I touch on the even more important general synthetic outcomes from ideas generated by the search for useful amounts of a cortically active hormone, such as novel angular methylations, partial hydrogenations of aromatic systems (Birch reductions), and novel usages in synthesis based on the unique structures so generated. The Birch process was critical for synthesis of the first oral contraceptives. A need to explain the structures of Birch reduction products and the experimental requirements resulted in further elucidations of the mechanism of reduction processes, notably for aromatic compounds. The first theoretical and practical distinction between structures of products as determined by a reaction rate or an equilibrium position was first exploited experimentally in the deconjugation of cholest-4-en-3-one in the final step of the first facile total synthesis of cholesterol. A knowledge gained of the biosynthesis of steroids and its specific enzymes helped to initiate my general polyketide theory of biosynthesis and also my idea of outdoing enzyme achievements with organometallic complexes ("inorganic enzyme chemistry"). I assert the high historic importance of steroids in promoting the advance of general organic chemistry within many fields. PMID- 1519268 TI - Sterol molecule: structure, biosynthesis, and function. AB - This review briefly summarizes key researches on the structure of the sterol molecule from its very beginnings to the definitive elucidation in 1932. Cholesterol biosynthesis treated in somewhat greater detail covers the period from the 1930s to the 1960s. As a historic contribution, it presents researches previously published in numerous books, reviews, and original papers. The selection of topics, dictated by limits of time and space, is necessarily arbitrary and a personal choice. Readers of this journal will be familiar with the relevant chemical structures. Structural formulas are therefore omitted. PMID- 1519269 TI - Hunt for an economical synthesis of cortisol: discovery of the fluorosteroids at Squibb (a personal account). PMID- 1519270 TI - Historic reflection on steroids: Lederle and personal aspects. AB - Steroid research at Lederle was initiated in 1946 and continued until about 1971. The areas of research interest involved primarily a study of delta 5,7-steroids, provitamin D3 variants, dehydroepiandrosterone variants, steroidal ketals, corticoids, and steroid conjugates. One of the principal goals was to develop novel antiinflammatory steroids for the treatment of, e.g., rheumatoid arthritis. A rational design led to the development of 16 alpha-hydroxycorticoids, culminating in the synthesis and therapeutic use of triamcinolone and related compounds. PMID- 1519271 TI - Early history of steroid chemistry in Mexico: the story of three remarkable men. PMID- 1519272 TI - From Ruzicka's terpenes in Zurich to Mexican steroids via Cuba. PMID- 1519273 TI - Abstracts of literature: to be or not to be? PMID- 1519274 TI - Silent stroke in patients with transient ischemic attack or minor ischemic stroke. The Dutch TIA Trial Study Group. AB - BACKGROUND AND PURPOSE: We studied silent stroke (i.e., infarcts on computed tomographic scan not related to later symptoms) in patients after transient ischemic attack or minor ischemic stroke. METHODS: Ours is a cross-sectional study of 2,329 patients who were randomized in a secondary prevention trial after transient ischemic attack or minor ischemic stroke and had no residual deficit after the qualifying event. RESULTS: Silent stroke was observed in 13% of the 2,329 patients. Lacunes formed 79%, cortical lesions 14%, and border zone lesions 7% of all silent strokes. Silent lacunes were most often located in the basal ganglia and symptomatic lacunes most often in the corona radiata. Age, hypertension, and current cigarette smoking were related to the presence of silent stroke. Silent stroke was equally common in different types of transient ischemic attack, including transient monocular blindness. Residual symptoms of any kind were more common in patients with silent stroke than in those without. CONCLUSIONS: Because only the sites of silent stroke infarcts differed slightly from those of symptomatic infarcts and the frequency of vascular risk factors was similar to that of symptomatic infarcts, silent stroke may have the same bearing on future risk as known prior stroke. PMID- 1519275 TI - Dementia associated with lacunar infarction. AB - BACKGROUND AND PURPOSE: The purpose of this study was to assess the number of patients with lacunar lesions who develop dementia and to evaluate in patients with and without dementia the relevance of risk factors for cerebrovascular disease, the occurrence of leukoaraiosis, the volume and location of vascular lesions, the size of ventricular and subarachnoid spaces, and stroke recurrence. METHODS: One hundred eight patients in whom computed tomograms revealed lacunar lesions that could account for their clinical neurological pictures were followed up for an average of 4 years after their first lacunar stroke. RESULTS: Twenty five patients (23.1%) developed dementia. The prognosis regarding occurrence of dementia during the follow-up period, evaluated by the Kaplan-Meier method, was significantly worse in subjects with the greatest evidence of cerebral atrophy (p less than 0.009) and in subjects who underwent new focal cerebrovascular episodes (p less than 0.000001). No differences were seen in the frequency of vascular risk factors or the site or volume of lesions between the demented and nondemented groups. CONCLUSIONS: Patients with lacunar infarcts suffer from dementia 4-12 times more frequently than the normal population. Cerebral atrophy and recurrent stroke, as well as other as-yet unclarified factors, are involved in producing dementia. PMID- 1519276 TI - Some epidemiological aspects of stroke: mortality/morbidity trends, age, sex, race, socioeconomic status. AB - BACKGROUND AND PURPOSE: The reasons for decreasing stroke mortality could be related to either decreasing incidence and/or improved prognosis. Thus far, secular trends of stroke have been analyzed either through mortality or morbidity data. This report examines both aspects simultaneously, on a nationwide basis, for the period 1968-1988. METHODS: Mortality statistics were based on the Compressed Mortality File. Estimates of morbidity were based on the National Hospital Discharge Survey. The Area Resource File was used to obtain county specific socioeconomic statistics. RESULTS: The decline in stroke mortality continued through the 1970s and 1980s, whereas morbidity remained constant and possibly even increased. Mortality and morbidity rates were similar in both sexes, higher in blacks, and lower in other (primarily Asian) Americans. There was an inverse correlation between death rates and socioeconomic status, which was particularly marked in blacks. Temporal decline occurred in all strata. CONCLUSIONS: The observed decrease in stroke mortality rates results most probably from an improved survival rather than from a decline in incidence. The abundance of new drugs and screening programs may not have affected the overall morbidity of stroke, possibly because of inefficient treatment regimens. PMID- 1519277 TI - Incidence of stroke in Taiwan. AB - BACKGROUND AND PURPOSE: Few epidemiological studies concerning the incidence of stroke have been conducted in Taiwan. In an attempt to investigate this common disease, we studied the incidence of stroke in Taiwan in a prospective incidence study. METHODS: A cohort of 8,562 stroke-free people were followed up for 4 years to observe new stroke occurrence. The methods of sampling the study population have been reported elsewhere. In addition to the help of local doctors, who reported the new stroke cases, we also sent public nurses to visit the study population annually to screen the new cases of stroke. RESULTS: There were 104 (61 men and 43 women) first-ever stroke cases identified by a neurologist in a period between October 1, 1986 and December 31, 1990. The average annual incidence rate of first-ever stroke for people aged 36 years or older in this study was 330 per 100,000. Incidence rate was higher in eastern Taiwan and in rural communities. Percentages of the major types of stroke were as follows: cerebral infarction, 71%; cerebral hemorrhage, 22%; subarachnoid hemorrhage, 1%; and unclassified, 6%. The significant risk factors for stroke were hypertension and intake of food with a high sodium content. CONCLUSIONS: The age-specific incidence rates in this study are higher than those reported from the United Kingdom and the United States. The rates are close to those in a report from Japan and a report from a city in mainland China at the same latitude. Cerebral hemorrhages are more common among people in Taiwan than among Occidental people. PMID- 1519278 TI - Cigarette smoking, alcohol use, and subarachnoid hemorrhage. AB - BACKGROUND AND PURPOSE: Subarachnoid hemorrhage remains a devastating disease. Identification of etiologic risk factors would allow the possibility of prevention. METHODS: We conducted a population-based case-control study in King County, Washington. Patients whose bleeds originated from a source other than an aneurysm were excluded. Two age- and gender-matched control subjects were identified for each case through random digit telephone dialing. A standardized in-person interview was conducted with the patient whenever possible, a proxy respondent for the case in all instances, the two control subjects, and their proxies. Analyses involved conditional logistic regression taking into account matching on age, gender and respondent type. RESULTS: Over 2 years, 169 cases were identified, and 149 participated in the case-control study. Compared with those who never smoked, the odds ratio for current heavy smokers (greater than 20 cigarettes/day) was 11.1 (95% confidence interval [CI], 5.0-24.9); for current light smokers (less than or equal to 20 cigarettes/day), 4.1 (95% CI, 2.3-7.3); and for former smokers, 1.8 (95% CI, 1.0-3.2). The risk associated with smoking was greatest in the 3 hours after a cigarette (odds ratio [OR] = 7.0; 95% CI, 3.7 13.1) and then fell, not reaching the risk in those who had never smoked until more than 10 years had passed since the last cigarette. Heavy alcohol use (greater than 2 drinks/day) was also associated with bleeds (OR = 2.2; 95% CI, 0.9-5.1, after adjusting for smoking status). These associations were not substantially altered after adjusting for several possible confounding factors, including a history of hypertension. CONCLUSIONS: Cigarette smoking and heavy alcohol use are associated with the occurrence of subarachnoid hemorrhage. PMID- 1519279 TI - Relationship of cardiac disease to stroke occurrence, recurrence, and mortality. AB - BACKGROUND AND PURPOSE: This is a study of cardiac diseases associated with the 1,382 cases of first cerebral infarction in residents of Rochester, Minn., during 1960-1984. METHODS: This is a population-based study in Rochester, Minn., for which the medical record-linkage system was used to identify cardiac disease among patients with first cerebral infarction. RESULTS: There were 318 patients (23%) who had at least one major potential cardiac source of emboli. The proportion of patients with a cardiac source of emboli was significantly higher among patients older than age 75 years (29%) than among younger patients (17%). The 30-day stroke recurrence rate among patients with a cardiac source of emboli (2%) was not significantly different than that among those without a cardiac source of emboli (2%). Among patients with a cardiac source of emboli, there was no difference in the probability of stroke at 30 days and at 90 days for those treated or not treated with anticoagulants. During the first 30 days after cerebral infarction, the risk of death in patients with a cardiac source of emboli (23%) was 14 times that of recurrent stroke. The risk of death at 30 days in patients without a cardiac source of emboli was 8%. CONCLUSIONS: Significant independent predictors of death (Cox proportional-hazards analysis) were age, prior myocardial infarction, atrial fibrillation present at onset of stroke, congestive heart failure before the stroke, and an age x congestive heart failure interaction. The only significant independent predictors of recurrent stroke were cardiac valve disease and congestive heart failure. PMID- 1519280 TI - Low and high density lipoprotein metabolism in atherothrombotic brain infarction. AB - BACKGROUND AND PURPOSE: Elevated low density lipoprotein and reduced high density lipoprotein cholesterol may increase the risk of atherothrombotic brain infarction, but the metabolic mechanisms accounting for this relation are poorly understood. METHODS: The kinetic parameters of low density and high density lipoprotein were studied in nine subjects with atherothrombotic brain infarction or identifiable (by noninvasive testing) extracranial occlusive disease and in 12 control subjects. Autologous iodine-125-labeled lipoproteins were injected intravenously. Blood samples were drawn 10 minutes after injection and periodically thereafter for 10 days. Kinetic parameters were calculated from the decay curves. RESULTS: The stroke-risk group showed significantly higher triglyceride (p less than 0.05), total cholesterol (p less than 0.02), and low density lipoprotein cholesterol (p less than 0.01). The fractional catabolic rate of low density lipoprotein was significantly lower (p less than 0.001) and the high density lipoprotein rate higher (p less than 0.02) in the stroke-risk group than in the control group. Regression analysis (using all subjects) of serum lipoproteins and their respective fractional catabolic rates correlated significantly (for low density lipoprotein, r = 0.684, p less than 0.001; for high density lipoprotein, r = 0.595, p less than 0.002). Mean percent stenosis showed a significant relation with triglyceride level (r = 0.678, p less than 0.01) and low density lipoprotein cholesterol (r = 0.535, p less than 0.02) but not with high density lipoprotein cholesterol. Mean percent stenosis also showed correlation with both fractional catabolic rate of low density lipoprotein (r = 0.667, p less than 0.002) and with serum high density lipoprotein levels (r = 0.504, p less than 0.02). CONCLUSIONS: Our study provides insights into the role of altered low and high density lipoprotein metabolism in the pathogenesis of carotid stenosis. The statistically significant association of serum lipoprotein metabolic rates with carotid stenosis, rather than their respective serum concentrations, implies that metabolic parameters may be more important in predicting stroke risk. PMID- 1519281 TI - Hyperhidrosis as a reflection of autonomic failure in patients with acute hemispheral brain infarction. An evaporimetric study. AB - BACKGROUND AND PURPOSE: Sweating dysfunction is one of the most frequently encountered symptoms of autonomic failure but has received scant attention in patients with cerebrovascular diseases. Our purpose was to evaluate the prevalence, pathogenesis, and clinical correlates of sweating dysfunction in stroke. METHODS: We studied sweating at baseline and after a heating stimulus in 53 patients with acute hemispheral brain infarction and in 40 healthy control subjects by using a quantitative evaporimetric method. RESULTS: Significant hyperhidrosis on the paretic side of the body was verified in 55% of the patients at baseline, in 74% after 5 minutes of heating, and in 77% after 10 minutes of heating. Hyperhidrosis was established throughout the body and correlated with the severity of paresis, the presence of reduced muscle tone, and the extensor plantar response. CONCLUSIONS: The phenomenon of hyperhidrosis in hemiparetic patients reflecting autonomic dysfunction seems to be a common manifestation that should be listed among the expected consequences of brain infarction. This sweating disturbance might be attributed to a lesion of a putative sympathoinhibitory pathway controlling sweating. The failure of this pathway could also be related to other manifestations of sympathetic hyperfunction, e.g., cardiac complications. Therefore, assessment of sweating may provide a new, important aspect in the evaluation of stroke patients. PMID- 1519282 TI - Low blood-to-cerebrospinal fluid passage of sorbitol after intravenous infusion. AB - BACKGROUND AND PURPOSE: Compared with mannitol, the osmotherapeutic agent sorbitol is less prone to accumulate in the blood and the same quantity may be infused in a smaller volume. Because of these advantageous characteristics, we studied the pharmacokinetics of sorbitol in serum and cerebrospinal fluid. METHODS: Six patients (five women and one man; age range, 46-70 years) with an external ventriculostomy and suffering from brain edema due to cerebrovascular disease received sorbitol as part of their therapy. Before and after the first dose of 50 g infused over 20 minutes, sorbitol concentrations in serum and cerebrospinal fluid were determined repeatedly using an enzymatic procedure. RESULTS: Maximal sorbitol concentrations ranged from 2,705 to 5,821 (median, 3,227) mg/l in serum compared with 6.7-130.7 (median, 19.5) mg/l in cerebrospinal fluid. Cerebrospinal fluid maxima were observed 0.17-3 hours after the end of the infusion. Sorbitol elimination in serum was adequately described by a two compartment pharmacokinetic model (distribution half-life, 0.05-0.14 hour; elimination half-life, 0.23-0.61 hour). Elimination in cerebrospinal fluid followed a single-exponential decay and was considerably slower than that in serum (half-life, 1.3-7.7 hours). CONCLUSIONS: The maximal cerebrospinal fluid concentration/maximal serum concentration ratio was low for sorbitol, thus suggesting a small potential risk of inducing an increase of intracranial pressure after osmotherapy (rebound effect). PMID- 1519283 TI - Evaluation of the vertebrobasilar-posterior system by transcranial color duplex sonography in adults. AB - BACKGROUND AND PURPOSE: The transcranial color duplex sonography technique was applied to the vertebrobasilar-posterior system to provide normal data for clinical application. METHODS: The intracranial posterior circulation was studied in 49 healthy volunteers (mean +/- SD age, 35 +/- 12 years) by a transcranial and suboccipital approach with a 2.0-MHz sector transducer of a computed sonography system. RESULTS: The posterior cerebral artery and the vertebrobasilar system were depicted clearly in the color Doppler mode. Pulsed Doppler signals could be recorded in the posterior cerebral (100%), basilar (92%), and vertebral arteries (89%). The following normal values were provided for all vessels: systolic peak, end-diastolic maximum, time-averaged, and time-averaged maximum velocities; resistance and pulsatility indexes; and a spectral broadening index. Mean +/- SD values were 45.9 +/- 9.6, 45.5 +/- 10.8, and 39.2 +/- 10.6 cm/sec for time averaged maximum velocity, and 28.3 +/- 6.5, 30.6 +/- 7.2, and 24.7 +/- 8.4 cm/sec for time-averaged velocity in the posterior cerebral, basilar, and vertebral arteries, respectively. In a reproducibility study, duplex measurements of the posterior cerebral arteries were repeated in 27 subjects. The correlation between the two examiners was high (r = 0.56, p less than or equal to 0.0001 for time-averaged maximum velocity). CONCLUSIONS: Color duplex sonography of the vertebrobasilar-posterior system is a new, noninvasive, bedside investigative technique. It permits visualization of artery flow in real time, relating these to adjacent brain and cranial structures, as well as angle-corrected duplex measurement of "true" flow velocities at defined sites of the vessels. Thus, it will open new diagnostic possibilities in disorders of the posterior circulation. PMID- 1519284 TI - A phenothiazine derivative reduces rat brain damage after global or focal ischemia. AB - BACKGROUND AND PURPOSE: We previously reported that 2-(10H-phenothiazin-2-yloxy) N,N-dimethylethanamine hydrochloride is a potent inhibitor of iron-dependent lipid peroxidation in vitro and can protect primary cultures of rat hippocampal neurons from hydrogen peroxide-induced toxicity. Because oxidants may play an important role in mediating postischemic tissue injury, we evaluated this agent in two rat models of transient cerebral ischemia. METHODS: In a model of global forebrain ischemia, 23 male Wistar rats were subjected to 10 minutes of four vessel occlusion followed by 72 hours of reperfusion. The rats received three intraperitoneal injections of either vehicle (2% aqueous acacia) or test agent (40 mg/kg). In a model of focal stroke, 19 spontaneously hypertensive rats were subjected to 2 hours of tandem middle cerebral and ipsilateral common carotid artery occlusion followed by 24 hours of reperfusion. The rats received three intraperitoneal injections of either vehicle (2% aqueous acacia) or test agent (40 mg/kg). RESULTS: In the global model, the phenothiazine significantly protected the CA1 layer of the hippocampus, with a reduction in mean damage score from 2.1 +/- 0.3 for control rats to 1.0 +/- 0.4 for treated rats (p less than 0.05). In the transient focal stroke model, the compound reduced cortical infarct volume from 130.1 +/- 10.3 mm3 for control rats to 95.2 +/- 24.5 mm3 for treated rats (p less than 0.02). CONCLUSIONS: Although the primary mechanism responsible for the protective effect is unclear at the present time, our study is consistent with the hypothesis that oxidant-mediated lipid peroxidation may be involved in the pathophysiology of postischemic brain injury. PMID- 1519285 TI - Distribution of the 72-kd heat-shock protein as a function of transient focal cerebral ischemia in rats. AB - BACKGROUND AND PURPOSE: The significance and physiological implications of the expression of the 72-kd heat-shock protein in ischemic tissue are unknown. To enhance our understanding of the relation between ischemic cell damage and 72-kd heat-shock protein expression, we evaluated the cellular expression and the anatomic distribution of 72-kd heat-shock protein in conjunction with the morphological analysis of rat brain, as a function of the duration of a single arterial occlusion. METHODS: Adult Wistar rats were subjected to graded transient middle cerebral artery occlusion (for a duration of 10, 20, 30, 60, 90, and 120 minutes and sham; n = 4 per group). Forty-eight hours after reopening the artery, brain tissue sections were analyzed to determine the extent of neuronal damage (hematoxylin and eosin staining), the extent of astrocytic reactivity (immunohistochemistry, using anti-glial fibrillary acidic protein), and the distribution of 72-kd heat-shock protein (immunohistochemistry, using a monoclonal antibody to 72-kd heat-shock protein). RESULTS: We found that 72-kd heat-shock protein was sequentially expressed in morphologically intact neurons, microglia, and endothelial cells with increasing duration of ischemia; 72-kd heat shock protein immunoreactivity was not detected in astrocytes. The duration of ischemia required to evoke a 72-kd heat-shock protein response in neurons was dependent on the anatomic site and followed a pattern of increasing neuronal sensitivity to ischemic cell damage with duration of ischemia: 72-kd heat-shock protein and neuronal damage were sequentially detected in the caudate putamen, globus pallidus, cerebral cortex, amygdala, and hippocampus with increasing duration of ischemia. With ischemia of long duration (greater than or equal to 90 minutes), neurons expressing 72-kd heat-shock protein were localized to a zone peripheral to the severely damaged ischemic core. CONCLUSIONS: These studies suggest that 1) the expression of 72-kd heat-shock protein in neurons precedes the development of ischemic cellular alterations detectable by conventional hematoxylin and eosin light microscopy methods; 2) there is a hierarchy of cell types and anatomic sites that express 72-kd heat-shock protein, and this hierarchy reflects cellular and anatomic vulnerability to ischemic cell damage; and 3) 72-kd heat-shock protein induction in neurons bordering a necrotic ischemic core may be the morphological equivalent of the ischemic penumbra. PMID- 1519286 TI - Magnetoencephalography of focal cerebral ischemia in rats. AB - BACKGROUND AND PURPOSE: The purpose of this study was to use magnetoencephalography to record magnetic field changes in the brain during middle cerebral artery occlusion. METHODS: A direct-current electrocorticogram (two channels) and a direct-current magnetoencephalogram (seven channels) were simultaneously recorded from five rats subjected to middle cerebral artery occlusion for 1-2 hours. RESULTS: Direct-current electrocorticographic and direct current magnetoencephalographic signal deflections were observed after the onset of middle cerebral artery occlusion and occurred repeatedly throughout the ischemic period, with a mean +/- SD time interval of 12 +/- 5 minutes. A one-to one correspondence of the electrocorticographic and magnetoencephalographic signal deflections was demonstrated. CONCLUSIONS: Direct-current magnetoencephalography can provide a new noninvasive technique for studying depolarization and/or spreading depression in focal cerebral ischemia. PMID- 1519287 TI - Reversible focal ischemic injury demonstrated by diffusion-weighted magnetic resonance imaging in rats. AB - BACKGROUND AND PURPOSE: Diffusion-weighted magnetic resonance imaging (DWI) can quantitatively display focal brain abnormalities within minutes after the onset of ischemia. We performed the present study to determine the effects of 1 and 2 hours of temporary ischemia on DWI. METHODS: We examined DWI and T2-weighted magnetic resonance images (T2WI) during and after 1 and 2 hours of temporary middle cerebral artery occlusion in rats (n = 10 for each group). In a subgroup of four animals from each group, we employed perfusion magnetic resonance imaging to monitor cerebral perfusion. Neurological outcome and infarct size after survival for 24 hours were compared between the groups and correlated with DWI and T2WI studies. RESULTS: Perfusion studies qualitatively documented hypoperfusion and reperfusion during and after temporary occlusion. Lesion size on DWI during reperfusion was significantly less than that during ischemia for 1 (55% decline, p less than 0.02) but not 2 hours of occlusion. The DWI signal intensity ratio (intensity compared with that in the contralateral homologous area) just before withdrawal of the occluder was significantly less in regions where the hyperintensity disappeared after withdrawal than in regions with persistent hyperintensity (p less than 0.002). The T2WI studies revealed few or no abnormalities, except after 2 hours of occlusion. The neurological outcome was significantly better in the 1-hour than in the 2-hour group (p less than 0.05). Postmortem infarct volume was significantly smaller in the 1-hour group than in the 2-hour group (p less than 0.05). The postwithdrawal DWI accurately predicted infarct size (R = 0.96, p less than 0.0001). CONCLUSIONS: The present study indicates that DWI can rapidly display not only irreversible but also reversible ischemic brain damage and enhances the importance of DWI as a diagnostic modality for stroke. PMID- 1519288 TI - Prevention of postischemic canine neurological injury through potentiation of brain energy metabolism by acetyl-L-carnitine. AB - BACKGROUND AND PURPOSE: Mechanisms of ischemia/reperfusion brain injury include altered patterns of energy metabolism that may be amenable to pharmacological manipulation. The purpose of this study was to test the effectiveness of postischemic acetyl-L-carnitine administration on potentiation of metabolic recovery and prevention of neurological morbidity in a clinically relevant model of complete, global cerebral ischemia and reperfusion. METHODS: Neurological deficit scoring as well as spectrophotometric and fluorescent assays of frontal cortex lactate and pyruvate levels were used in a canine model employing 10 minutes of cardiac arrest followed by restoration of spontaneous circulation for 2 or 24 hours. RESULTS: Dogs treated with acetyl-L-carnitine exhibited significantly lower neurological deficit scores (p = 0.0037) and more normal cerebral cortex lactate/pyruvate ratios than did vehicle-treated control animals. CONCLUSIONS: Postischemic administration of acetyl-L-carnitine potentiates normalization of brain energy metabolites and substantially improves neurological outcome in a clinically relevant model of global cerebral ischemia and reperfusion. PMID- 1519289 TI - Neuroprotective mechanism of (+)SKF 10,047 in vitro and in gerbil global brain ischemia. AB - BACKGROUND AND PURPOSE: The N-methyl-D-aspartate receptor is believed to mediate part of the ischemic neuronal damage caused by the excitatory amino acid glutamate. (+)SKF 10,047, the prototypic sigma-agonist, interacts with the N methyl-D-aspartate receptor. Therefore, we studied the neuroprotective effect of (+)SKF 10,047 on cultured rat cerebellar neurons and on CA1 hippocampal neurons of gerbils exposed to brain ischemia. METHODS: Mechanisms of neuroprotection were studied in vitro by measuring calcium influx into cultured rat cerebellar granule cells loaded with fura 2-AM. In vivo neuroprotection of gerbil CA1 hippocampal neurons was studied in a posttreatment regimen following 5 minutes of bilateral carotid artery occlusion and 7 days of reperfusion. RESULTS: In primary cultured rat cerebellar granule cell neurons, (+)SKF 10,047 in a dose-dependent manner diminished intracellular calcium levels of N-methyl-D-aspartate-stimulated neurons by a maximum of 87% (n = 8), with a 50% inhibitory concentration of 0.8 microM. (+)SKF 10,047 did not prevent subsequent calcium influx stimulated by kainic acid or KCl, nor did it interfere with modulation of the kainate response by quisqualic acid. Neuroprotection of 64% (p = 0.006, n = 15) of gerbil CA1 hippocampal neurons was achieved by posttreatment injection followed by minipump infusion. CONCLUSIONS: Neuroprotection by (+)SKF 10,047 most likely involves interaction at the N-methyl-D-aspartate receptor. These results suggest that the benzomorphan class of sigma-agonists may provide neuroprotection in cerebral ischemia and stroke. PMID- 1519290 TI - Increases in cerebral blood flow in rat hippocampus after medial septal injection of naloxone. AB - BACKGROUND AND PURPOSE: In a previous study, we occasionally found that the rat given naloxone in the preoptic region develops behavioral seizures. In view of knowledge that the forebrain including the medial septal nucleus provides cholinergic projections to the hippocampal formation, the present study examined the effects of naloxone injected into the medial septal nucleus on the local blood flow in the hippocampus. METHODS: A polyurethane-coated platinum electrode with a 1-mm bare tip for measurement of blood flow and a guide cannula made of stainless steel tube for naloxone injection were implanted chronically into the brain. The cerebral blood flow was measured by the hydrogen clearance method in freely moving rats. RESULTS: The injection of 50 micrograms naloxone caused a significant increase in hippocampal blood flow, with its peak at 20 minutes. Twenty micrograms naloxone caused a similar increase, but 10 micrograms caused only a slight increase that peaked at 30 minutes, suggesting a dose-response of naloxone effect. Hippocampal blood flow was not changed after the injection of saline into the medial septal nucleus and after the injection of naloxone into the caudate nucleus. CONCLUSIONS: Taken together with previous findings, the results suggest that endogenous opioids exert a decreasing effect on the local blood flow in the hippocampus, probably mediated by the magnocellular cholinergic neurons projecting to the hippocampus. PMID- 1519291 TI - Laser doppler flowmetry in CA1 sector of hippocampus and cortex after transient forebrain ischemia in gerbils. AB - BACKGROUND AND PURPOSE: Local differences in the hemodynamic response to transient ischemia could be involved in the development of selective vulnerability. These differences were studied in vulnerable and nonvulnerable regions of the brain. METHODS: Five gerbils were subjected to 10 minutes of bilateral forebrain ischemia, and cerebral blood flow was measured continuously in the frontal cortex and CA1 sector of the hippocampus using laser Doppler flowmetry. Carotid artery pressure was recorded simultaneously with a pressure transducer. RESULTS: After induction of ischemia, blood flow in the cortex and CA1 sector decreased to 11.8% and 18.0% of the baseline value, respectively. After release of the vascular occlusion, blood flow in the cortex returned to the preischemic level at 7.5 minutes (recovery time), reached the hyperemic peak (123.8%) at 12.4 minutes (peak latency), and again decreased to the preischemic level at 27.2 minutes. In the CA1 sector, blood flow returned to the preischemic level at 2.1 minutes, reached the hyperemic peak (122.2%) at 5.7 minutes, and decreased again to the preischemic level at 21.3 minutes. In both the cortex and CA1 sector, recovery time and peak latency correlated inversely with the amount of residual blood flow during ischemia. Histologically, cortical neurons were not injured but only 14.6% of CA1 neurons survived 1 week after ischemia. CONCLUSIONS: CA1 neurons were selectively injured despite the milder percentage decrease of blood flow during ischemia and the more prompt recovery of flow after ischemia. These findings stress the importance of intrinsic rather than hemodynamic factors in the pathogenesis of selective vulnerability of CA1 neurons after transient bilateral forebrain ischemia. PMID- 1519292 TI - Level of function predicts first stroke in the elderly. AB - BACKGROUND AND PURPOSE: Our aim in this study was to assess physical function as a predictor of stroke incidence in a probability sample of noninstitutionalized elderly subjects with no previous history of stroke. SUMMARY OF REPORT: The data were obtained from a prospective longitudinal study of 2,812 individuals aged 65 years of age and older living in New Haven, Connecticut. Incidence of stroke was monitored from the baseline interview in 1982 until December 1988 (n = 167). Physical function was measured by the Katz scale of activities of daily living and a three-item scale measuring gross mobility function (Rosow scale). Both measures of impairment of function were independently associated with stroke incidence controlling for age, sex, diabetes, hypertension, and angina (p less than 0.001). CONCLUSIONS: Our findings suggest that in elderly persons, physical disability is a newly identified risk factor for stroke. PMID- 1519293 TI - The preponderance of posterior circulatory events is independent of the route of cardiac catheterization. AB - BACKGROUND AND PURPOSE: Central nervous system complications of cardiac catheterization are most often attributed to embolic events that occur at the time of catheter manipulation. Nevertheless, the reason that over 50% of these events are localized to the posterior circulation remains unexplained. One potential explanation offered for this preponderance is the use of the brachial artery approach. In this report, we examined the relation between the route of catheterization and central nervous system complications. SUMMARY OF REPORT: We retrospectively analyzed all central nervous system complications that occurred after cardiac catheterization through a femoral route at our institution over a 3 1/2-year period. Thirteen patients were identified as having central nervous system complications. Using defined criteria, posterior circulatory events still accounted for at least 54% of central nervous system complications. CONCLUSIONS: The preponderance of posterior circulatory events is apparently independent of the route of catheterization. Furthermore, given the array of neurological symptoms and their often complete resolution, we feel it is unlikely that embolism is the sole pathophysiological mechanism involved in these events. PMID- 1519294 TI - Caudate hemorrhage with moyamoya-like vasculopathy from atherosclerotic disease. AB - BACKGROUND AND PURPOSE: Caudate hemorrhage usually results from hypertension, rupture of arteriovenous malformation or aneurysm, or rarely, moyamoya disease. Moyamoya-like changes related to severe atherosclerotic occlusive disease, usually causing ischemic stroke, have been reported. CASE DESCRIPTION: A 51-year old normotensive patient was admitted with headache due to a left caudate hematoma with ventricular extension. There was a history of smoking, leg claudication, elevated cholesterol, and coronary artery disease. Angiography demonstrated complete extracranial carotid occlusion on the left and atherosclerotic stenosis at the bifurcation on the right, with supraophthalmic occlusion distally. At the base of the brain, bilateral moyamoya-like vessels, presumed to be secondary to atherosclerotic occlusion, were evident, but neither aneurysm nor arteriovenous malformation was present. Cerebral blood flow and transcranial Doppler studies indicated severely impaired cerebral perfusion that improved after bilateral extracranial-to-intracranial bypass surgery. CONCLUSIONS: Atherosclerotic occlusive carotid disease with moyamoya-like changes may be a rare cause of caudate hemorrhage. A decrease in moyamoya vessels with bypass surgery may reduce the risk of recurrent hemorrhage. PMID- 1519295 TI - Postpartum cerebral angiopathy with cerebral infarction due to ergonovine use. AB - BACKGROUND AND PURPOSE: Earlier cases of stroke due to postpartum cerebral angiopathy have been reported. The mechanism of this angiopathy has not been explained. CASE DESCRIPTION: We present a case of cerebral infarction with evidence of occlusive change in the vertebrobasilar system as a complication of intravenous ergonovine use after cesarean section delivery. CONCLUSIONS: Ergonovine therapy is a likely cause of so-called postpartum cerebral angiopathy and stroke. PMID- 1519296 TI - Polymorphonuclear leukocytes and monocytes/macrophages in the pathogenesis of cerebral ischemia and stroke. AB - BACKGROUND: The extent to which polymorphonuclear leukocytes and monocytes/macrophages contribute to the pathobiology of cerebral ischemia and stroke is an issue of long-standing contradiction and controversy. Recent developments in the ability to selectively modify leukocyte adhesion with antiadhesion antibodies and the potential clinical application of this therapeutic approach have spurred a resurgence of experimental studies examining the role of leukocytes in cerebral ischemia and stroke. SUMMARY OF REVIEW: We review studies examining leukocyte accumulation, initiation of thrombosis, and exacerbation of ischemic brain injury in stroke, and we examine other proposed contributions of leukocytes to cerebrovascular pathophysiology. CONCLUSIONS: The importance of specific characteristics of a given ischemia model and of underlying stroke risk factors in determining the degree of leukocyte involvement and effectiveness of therapies directed against these cells is discussed. PMID- 1519297 TI - Cerebral infarction and nephrotic syndrome. PMID- 1519298 TI - Stroke following marijuana smoking. PMID- 1519299 TI - Interactions between clobazam and standard antiepileptic drugs in patients with epilepsy. AB - We retrospectively collected plasma level assessments performed in 96 adult patients with epilepsy on stable monotherapy, including 9 patients on clobazam (CLB), 34 on carbamazepine (CBZ), 24 on phenobarbital (PB), 9 on phenytoin (PHT), and 20 on valproate (VPA); these results were compared to those obtained in 54 adult patients on stable bitherapy with the association of CLB with either CBZ (n = 17), PB (n = 17), PHT (n = 5), or VPA (n = 15). Our results show that CLB has no significant effect on the level to dose ratio (LDR) of CBZ, PB, PHT, or VPA. Conversely, CBZ, PB, and PHT significantly decrease the LDR of CLB. CBZ and PHT significantly increase the LDR of N-desmethylclobazam (NCLB), the major metabolite of CLB. A significant increase in the NCLB/CLB ratio was found in CBZ + CLB, PB + CLB, and PHT + CLB bitherapies. These findings are of clinical significance: clobazam is useful as adjunctive treatment in human epilepsy and is often chosen as the benzodiazepine adjunctive drug in chronic resistant epilepsy. Sedative side effects may occur, especially in patients treated by a CBZ + CLB or PHT + CLB bitherapy, and both CLB and NCLB plasma levels should be monitored in such patients. PMID- 1519300 TI - Blood cyclosporin concentrations but not doses correlate with acute changes in renal function following heart and heart-lung transplantation. AB - The relationship between changes in cyclosporin (CyA) dose or CyA blood concentration and the reciprocal creatinine concentration was investigated by cross-correlation analysis over the first 3 postoperative months in 32 consecutive heart and heart-lung recipients. Exploratory analysis suggested that early changes in renal function, probably attributable to recovery from preoperative cardiac failure, obscured later underlying correlations. Therefore, all data up to the first nadir in plasma creatinine following transplantation were excluded from the analysis. Five-day mean CyA doses or blood concentrations were cross-correlated with 5-day mean reciprocal creatinine concentrations measured either in the same 5-day period or with the creatinine measured up to two 5-day periods later. Although a significant correlation was found between CyA dose and blood concentration (the 95% confidence interval of the population correlation coefficient did not overlap zero), there was no relationship between dose and changes in renal function. The blood CyA concentration, however, correlated significantly with the reciprocal creatinine concentration measured in the same 5-day period and was also predictive of changes in creatinine measured in the subsequent 5-day period. Thus, a major criterion for therapeutic drug monitoring had been fulfilled: CyA dosage adjustment based on blood CyA concentrations, as the intermediate therapeutic end point, is helpful in the management of acute nephrotoxicity in heart and heart-lung transplant recipients because of the lack of a dose-effect relationship. Regular CyA monitoring and appropriate dosage adjustment is essential for the management of acute nephrotoxicity in the first 3 months following heart or heart-lung transplantation. PMID- 1519301 TI - Pharmacokinetics of zidovudine phosphorylation in patients infected with the human immunodeficiency virus. AB - The relationship between zidovudine phosphorylation inside mononuclear cells and plasma zidovudine pharmacokinetic was assessed in six subjects. Plasma and intracellular concentrations were measured by radioimmunoassay over an 8-h period after administration of 100 or 200 mg of zidovudine. Plasma pharmacokinetics followed expected patterns, with considerable interpatient variability in area under the concentration-versus-time curve (AUC), and a terminal half-life of 1.5 h. Intracellular AUC was even more variable than plasma AUC, but the data suggested a crude linear relationship between these parameters. The intracellular half-life of 3.5 h was consistently longer than the plasma half-life, and varied little between patients. The prolonged intracellular half-life suggested that total phosphorylated zidovudine, as measured by the method described, is not greatly dominated by the 5'-monophosphate as predicted from the in vitro studies reported in the literature. Plasma concentrations of zidovudine have shown little correlation with clinical effect. Study of the relationship between phosphorylated zidovudine and clinical outcome could lead to a more effective management of therapy. PMID- 1519302 TI - Predictive performance of Bayesian and nonlinear least-squares regression programs for lidocaine. AB - The predictive performance of two computer programs for lidocaine dosing were evaluated. Two-compartment Bayesian and nonlinear least-squares regression programs were used in two groups of patients (15 acute arrhythmia patients and 14 chronic arrhythmia patients). Lidocaine was given as a 1.5 mg/kg bolus and a 2.8 mg/min infusion for 48 h. A second bolus (0.5 mg/kg) was given 10 min after the first bolus over 2 min. Serum samples of the patients receiving lidocaine were drawn at 2, 15, 30 min and 1, 2, and 4 h and were used in forecasting the serum concentrations at 6, 8, 12, and 48 h. Predictive performance was assessed by mean error and mean-squared error. The results (mean +/- 95% confidence intervals) demonstrated the Bayesian program predicted a significant (p less than 0.05) difference at 12 h between the two arrhythmia groups (acute 0.52 [-0.95; -0.09] and chronic 0.28 [0.12; 0.44]). The results also demonstrated the Bayesian method was significantly more precise compared to the nonlinear least-squares regression program at 8, 12, and 48 h for the acute group. While caution is warranted, this study demonstrated that the predictive performance by a two-compartment Bayesian model is more accurate in predicting future lidocaine serum concentrations than that by nonlinear least-squares regression. PMID- 1519303 TI - Specific monoclonal radioimmunoassay and fluorescence polarization immunoassay for trough concentration and area-under-the-curve monitoring of cyclosporine in renal transplantation. AB - In order to study the performance of a specific fluorescence polarization immunoassay (FPIA) for monitoring of the area under the concentration time curve (AUC) of cyclosporine (CsA), a total of 170 24-h CsA AUC studies were prospectively collected from 40 consecutive adult renal transplant recipients during the first 6 months after transplantation. Each AUC study included whole blood samples that had been collected at 0, 2, 4, 6, 10, 14, and 24 h after CsA administration. Each sample was subjected to CsA analysis in whole blood using a 3H-tracer specific monoclonal radioimmunoassay (wb-sRIA), specific FPIA (wb sFPIA), and polyclonal FPIA (wb-pcFPIA). Furthermore, the performance of the specific assays was assessed against high-performance liquid chromatography (HPLC). Correlations between HPLC and specific assays were good, namely correlation coefficients of 0.94. Contrariwise, correlations between specific and nonspecific assay were poorer. As compared to HPLC, wb-sRIA overestimated CsA concentrations by 7.0%, and wb-sFPIA overestimated concentrations by 26.8%. The correlation between the AUC of CsA, as determined by wb-sRIA and wb-sFPIA, was excellent (r = 0.96). The ratio between wb-sFPIA and wb-sRIA was higher at low concentrations and small AUCs of CsA. On the average, CsA AUCs were 14% larger when assayed by wb-sFPIA. However, the appearance of the CsA concentration versus time curve was almost identical for the two assays. The apparent oral clearance (clearance/bioavailability) of CsA decreased with time after transplantation. Furthermore, the oral clearance of CsA was significantly higher in patients experiencing acute rejection than in those who were quiescent (p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1519304 TI - Performance of a fluorescence polarization immunoassay system evaluated by therapeutic monitoring of four drugs. AB - Fluorescence polarization immunoassays (FPIA) for amikacin, gentamicin, quinidine, and theophylline (supplied by Roche Diagnostic Systems, made using a Cobas Fara centrifugal analyzer) were evaluated and compared with widely used monitoring analysis methods. For each drug, the between-assay imprecision was ascertained by calibration on the day of assay and by a stored calibration curve made at the beginning of the study. The precision of the amikacin and theophylline assays was acceptable [total coefficient of variation (CV) less than 7.5%] at all concentrations tested for each calibration mode. Imprecision of quinidine and gentamicin assays was significant at low concentrations (1.9 mg/L): total CV = 9.0% for quinidine assessed with stored calibration curve and total CV greater than 8.5% for gentamicin measured with the two calibration modes. The calibration curves for all four assays had a good stability (greater than 30 days). Linear regression analysis demonstrated close agreement between the FPIA (y) and the following comparative techniques (x): Abbott TDx assay for amikacin and gentamicin (r = 0.988, r = 0.974, respectively); Stratus fluorometric enzyme immunoassay for quinidine (r = 0.979); and EMIT Syva assay for theophylline (r = 0.993). It is concluded that fluorescence polarization immunoassay is a rapid and reliable method for the therapeutic monitoring of the four drugs tested. Moreover, the use of reagents on an instrument that can be implemented for a wide range of chemistries has significant advantages and cost benefits over dedicated instruments. PMID- 1519305 TI - Determination of fluconazole in human serum by solid-phase extraction and reversed-phase high-performance liquid chromatography. AB - A simple, rapid, and accurate reversed-phase octadecylsilyl high-performance liquid chromatographic method using solid-phase column extraction is described for measuring fluconazole in human serum. The column eluent was monitored by ultraviolet absorption at 210 nm. Fluconazole was extracted from diluted serum by adsorption on a small Bond-Elut C18 cartridge after the addition of UK48,134 as the internal standard and recovered by elution with methanol. The methanol was then evaporated to dryness and the residue reconstituted in 200 microliters of mobile phase and filtered prior to injecting an aliquot (50 microliters) onto an Adsorbosphere C18 column (4.6 x 250 mm, 5 microns particle size), using a mobile phase of 25 mM tris(hydroxymethyl)aminomethane-phosphate buffer (pH 7.0):acetonitrile (75:25, vol/vol). The retention times were 6.6 min for fluconazole and 9.0 min for the internal standard. The assay was precise, with inter- and intraassay coefficients of variation of less than or equal to 2.9% and less than or equal to 2.1%, respectively, and with good linearity (r = 1.000) in the range of 0.1 to 25 micrograms/ml. The duration of each analysis was 15 min and the minimum detectable serum concentration was 0.1 microgram/ml. PMID- 1519306 TI - A quick, sensitive high-performance liquid chromatography assay for monoethylglycinexylidide and lignocaine in serum/plasma using solid-phase extraction. AB - Recent advances in the investigation of liver disease and transplantation have seen the introduction of lignocaine as a probe of liver function. For this purpose, an assay that is sensitive and rapid is required for the major metabolite of lignocaine, monoethylglycinexylidide (MEGX). We have developed an accurate, low-cost high-performance liquid chromatography (HPLC) method using Bond-Elut phenyl (1 cc) cartridges for sample preparation. The total preparation time for five samples is less than 10 min and the run time is approximately 10 min/sample. Each cartridge can be used at least four times. Simultaneous measurement of another metabolite of lignocaine, glycinexylidide (GX), can be achieved by adjustment of the mobile phase and flow rate. The chromatogram is monitored with an UV detector at 210 nm. The inter- and intra-assay coefficients of variation for MEGX (10-250 micrograms/L) and lignocaine (100-2,000 micrograms/L) are less than 9.5 and less than 2%, respectively, with recoveries for MEGX, trimethoprim (internal standard), and lignocaine all greater than 85%. This method offers a rapid, sensitive assay that is clinically useful in the new role for lignocaine/MEGX in dynamic liver function testing. PMID- 1519307 TI - Rapid and sensitive liquid chromatographic assay of mefenamic acid in plasma. AB - Mefenamic acid (MA) is a nonsteroidal antiinflammatory analgesic agent widely used clinically. A simple and sensitive liquid-chromatographic assay has been developed for the quantitative determination of MA in human plasma. A reverse phase, 10-microns cyano column (25 x 0.4 cm), a mobile phase of water acetonitrile-methanol-17 M acetic acid (69:15:15:1 by volume), and an ultraviolet detection (290 nm) are used for the separation of MA and internal standard (methyl-clonazepam). MA and internal standard are extracted from acidified plasma into diethyl ether and after evaporation of the organic phase, the residue is redissolved in methanol. Calibration curves are linear in the range 0.05-3.20 micrograms/ml, and at the plasma level corresponding to the quantification limit (0.05 microgram/ml) coefficients of variation are 7.5% and 10.2% for repeatability and reproducibility studies, respectively. This assay was successfully used in the study of pharmacokinetics of MA in human plasma after a single oral administration of a low MA dose. PMID- 1519308 TI - Comparison of cyclosporine measurement in whole blood by high-performance liquid chromatography, monoclonal fluorescence polarization immunoassay, and monoclonal enzyme-multiplied immunoassay. AB - Monitoring of cyclosporine concentrations in whole blood is used routinely as a guide to adjusting dose so as to achieve optimal therapeutic benefit with minimal adverse effects. In the present study, we have compared a specific high performance liquid chromatography (HPLC) assay with a fluorescence polarization immunoassay (TDx) and an enzyme-multiplied immunoassay (Emit). Both Emit and TDx assays employ a monoclonal antibody to cyclosporin A and therefore have the potential for a high degree of specificity. Blood specimens (EDTA as anticoagulant) were obtained from 113 patients (71 renal transplants, 17 liver transplants, and 25 other categories) taking cyclosporine and analysed by all three methods. There were significant correlations between results for HPLC and Emit (Emit = 10.54 + 1.07 x HPLC; r2 = 0.82, p less than 0.001) and between results for HPLC and TDx (TDx = 9.16 + 1.42 x HPLC; r2 = 0.82, p less than 0.001). Compared to HPLC analysis, 74% and 96%, respectively, of Emit and TDx results were to the left of the line of identity. The TDx monoclonal antibody appears to have a lesser degree of specificity than that used in the Emit assay. Mean concentrations of cyclosporine measured by Emit and TDx were 17% and 51% higher, respectively, than those measured by HPLC. Because of this overestimation, we suggest that both Emit and TDx methods may find their most appropriate use in routine therapeutic monitoring of renal transplant patients in whom metabolite concentrations are less variable over time. PMID- 1519309 TI - Is the monoclonal fluorescence polarization immunoassay for cyclosporine specific? Comparison with specific radioimmunoassay. AB - Trough concentrations of cyclosporine (CsA) in whole blood were measured by specific monoclonal 3H-radioimmunoassay (S-RIA) and compared with those obtained by monoclonal fluorescence polarization immunoassay (S-FPIA) in 89 transplant recipients. Differences in the S-RIA:S-FPIA relationship between kidney transplant (KT, n = 59) and heart transplant (HT, n = 24) recipients were investigated. Mean concentrations of CsA were significantly higher by S-FPIA than by S-RIA [191 +/- 127 vs. 166 +/- 124 ng/ml (mean +/- SD), p less than 0.001], with a S-FPIA:S-RIA ratio of 1.25 +/- 0.33. Higher ratios were observed either in patients with low CsA concentrations or in those with a high proportion of metabolites. HT recipients had higher S-FPIA:S-RIA ratios than did KT recipients (1.37 vs. 1.22, t = 1.87, p = 0.065). Within-assay coefficients of variation were lower for S-FPIA than for S-RIA (2.4% vs. 12.3%, p less than 0.001). Monoclonal FPIA is a precise and fast method, more suitable than RIA for therapeutic CsA monitoring in clinical practice. However, our results indicate a 25% higher mean CsA concentration by S-FPIA than by S-RIA (37% in HT recipients), which should be borne in mind until therapeutic and toxic ranges are established or a more specific FPIA method is developed. PMID- 1519310 TI - Interaction of tricyclic antidepressants with cholestyramine in vitro. AB - The adsorption of amitriptyline, desipramine, doxepin, imipramine, and nortriptyline onto cholestyramine was demonstrated in vitro with use of 1.2 mol/L HCl at 37 degrees C to simulate gastric fluid. Binding to cholestyramine was approximately 80% for each of the tricyclic antidepressants, and this was about the same degree of binding noted with a nonpharmaceutical, non-ionic resin widely used in the diagnostic toxicology laboratory (Amberlite XAD-2). In contrast, five other non-antidepressants (acetaminophen, chlordiazepoxide, procainamide, quinidine, and theophylline) showed only minimal binding to cholestyramine under these conditions. Activated charcoal completely bound all drugs studied. These findings suggest that cholestyramine should be used with caution in patients receiving tricyclic antidepressants. They also suggest that cholestyramine may be a potentially useful adjunctive therapy in treatment of overdose with the tricyclic antidepressants. PMID- 1519311 TI - Effect of pH changes and ethanol on the binding of tricyclic antidepressants to cholestyramine in simulated gastric fluid. AB - Tricyclic antidepressants have previously been shown by this laboratory to bind significantly (greater than 80%) to cholestyramine in 1.2 mol/L HCl, used to simulate gastric fluid. This finding has important implications for individuals using tricyclic and cholestyramine concurrently, and it may also have potential therapeutic implications in the treatment of tricyclic overdose. In the present study the effects of pH changes and ethanol on this binding were evaluated. Percent binding of amitriptyline, desipramine, doxepin, imipramine, and nortriptyline decreased from 75-90% (pH 1.0) to 35-50% (pH 4.0). Beyond pH 4.0, however, the binding of each antidepressant increased up to 60-75% at pH 6.5. In contrast, ethanol consistently reduced the percent binding of each antidepressant to cholestyramine in 1.2 mol/L HCl until, in the presence of pure ethanol, the binding ranged from 0% (nortriptyline) to only 32% (doxepin). These findings are important since pH varies widely within the gastrointestinal tract and since ethanol may be co-ingested with cholestyramine and antidepressants. PMID- 1519312 TI - Effects of 2-acetyl-4-tetrahydroxybutyl imidazole (THI) on the thymus of rats. AB - 2-Acetyl-4-tetrahydroxybutyl imidazole (THI), a component of the food colouring ammonia caramel, has been shown to produce suppression of cell-mediated immunity and a reduction in circulating TH and TC/S lymphocytes in rats. Accordingly in this study the effects of THI on the thymus has been investigated. THI (1 mg/kg/day) was given for up to 7 days in the drinking water to Fischer 344 rats on a vitamin B6 deficient diet. No marked change in thymus weight was found but the cellularity was marginally decreased and flow cytometric analysis of the lymphocyte subsets revealed an increase in the number of CD4+CD8- and CD4-CD8+ single positive (SP) cells and a reduction in the number of CD4+CD8+ double positive (DP) thymocytes. This reduction was in agreement with histological findings of increased numbers of pyknotic cells in the cortex, mainly engulfed by macrophages. Mitogen-induced proliferation of thymocytes prepared from THI treated animals was increased, concordant with the gradual increase in the percentage of mature SP cells. No change in normal proliferation of thymocytes cultured in vitro, or, in proliferation in vivo, detected as 5-bromo-2' deoxyuridine (BrdU) incorporation, was found. It is concluded that THI produced an increase in death of immature DP cells. However, THI did not affect thymocyte proliferation or their differentiation into mature SP cells in the thymus, but rather impairs their migration into the circulation. The mechanism of action of THI appears to be indirect, but THI does not act through increasing the release of adrenal corticosteroids to supra-physiological levels as the same histopathological changes in the thymus were found in adrenalectomized rats. PMID- 1519313 TI - The influence of thymus extracts on the chemotaxis of polymorphonuclear neutrophils (PMN) from patients with insulin-dependent diabetes mellitus (IDD). AB - The main goal of this study was to evaluate the possible influence of thymus extracts on the chemotaxis of PMN isolated from diabetic patients. The analyzed group consisted of fifty patients with insulin-dependent diabetes mellitus (IDD), and twenty healthy adults were taken as controls. The results showed, that PMN isolated from patients with IDD manifested the impaired chemotaxis toward zymosan activated plasma (ZAP), plasma incubated with cellophane and supernate from E. coli culture. Both thymus extracts did not change the directed migration toward control plasma and toward ZAP. THYMEX-L did improve the migration of diabetic PMN toward plasma incubated with cellophane, whereas TFX-THYMOMODULIN ameliorated the impaired chemotaxis toward supernate from E. coli culture. Both thymus extracts can attract PMN obtained from healthy donors, but not the cells isolated from diabetic patients. PMID- 1519314 TI - 5-Lipoxygenase gene expression in the thymus. AB - Eicosanoids are arachidonic acid metabolites issued both the cyclooxygenase and the lipoxygenase pathways. Many of these products were reported to modulate the immune response. Since most of eicosanoids have a short half life they are considered as local immunomodulators. Interactions between eicosanoids and thymocytes appear to be complex within the thymus. It was reported that cyclooxegenase derivatives of arachidonic acid are produced in this primary lymphoid organ mostly by cells of the thymic microenvironment. On the other hand it is not yet clearly established (1) what is the location of the lipoxygenase positive cells within the gland and (2) what is the ratio of cells producing lipoxygenase metabolites of arachidonic acid when compared to the whole thymocyte population. Using two oligonucleotides complementary to the rat 5-lipoxygenase mRNA we demonstrated (by both hybridization on Northern blots and in situ hybridization) the expression of the 5-lipoxygenase gene in the thymus. 5 lipoxygenase positive cells appear to be associated in "clusters" and are mostly located in the thymic cortex. It is likely that they belong to the thymic microenvironment. PMID- 1519315 TI - Adenine nucleotide content of thymoma-derived lymphocytes. AB - Purine and pyrimidine metabolites are essential substances for cells. We have measured the adenine nucleotide (AN) contents of thymocytes from 15 human thymomas, 11 adjacent non-neoplastic thymuses and 3 children's thymuses. There was no significant difference in AN content of thymocytes between thymoma and children's thymus. But, AN content of adjacent non-neoplastic thymuses was significantly lower than that of thymoma or children's thymus. In mixed type thymoma, ATP content in thymocytes was significantly higher than that in lymphocytic type thymoma. These data indicate that thymocytes in thymoma may show further T cell maturation probably associated with the functional microenvironment of the neoplastic epithelial cells just like the children's thymus. PMID- 1519316 TI - Localization of estrogen receptors and estrogen receptor-mRNA in female mouse thymus. AB - The present study was performed to demonstrate estrogen receptor (ER) and ER-mRNA in female mouse thymus. The results are as follows: (i) thymic tissue contains ER in both reticuloepithelial(RE)- and T-cell fractions, the ER level being three fold higher in the former fraction than in the latter; and (ii) thymic tissue contains ER-mRNA at 6.2 kb, a large amount of which was localized in the RE cells and less in the T cells. From these results it is suggested that estrogen (E) mediates some immune function of the mouse thymus through its receptor within RE cells and/or T cells. PMID- 1519317 TI - Metoclopramide increases the number of solid epithelial islands in the adult rat thymuses. AB - The effect metoclopramide on thymocyte proliferation and the histological picture of the rat thymuses was investigated. A significant increase in the epithelial component of the thymus was found. On the other hand, metoclopramide administration did not influence the thymocyte proliferation. PMID- 1519318 TI - The ontogeny of bovine thymostimulin production in fetal and postnatal age. AB - The development of thymostimulin production in the bovine fetal thymus was determined, starting at month 2 of gestation until birth. Production of fetal thymostimulin, identified electrophoretically as a peptide with 4-5000 Da, started at month 4 of gestation and achieved its maximum expression three months after birth, followed by a rapid decrease until month 18. Thymus of fetuses from the early gestational phase (2-3 months) yielded no electrophoretically detectable thymostimulin band. Biological activity of the fractions, determined by increased E-rosetting, fairly correspond to the content of the 4-5000 Da peptide moiety. PMID- 1519319 TI - Immunodeficiency, growth hormone deficiency and central nervous system involvement in a girl. AB - We describe a mentally retarded 12-year-old girl with ataxia in whom diagnostic evaluation for short stature revealed isolated growth hormone (GH) deficiency and multiple central nervous system (CNS) lesions. Assessment of immunologic status, performed because of the persistence of recurrent respiratory tract infections, showed associated deficiencies of IgG2-IgG4 and specific antibody response; in addition, in vitro lymphocyte response to mitogens was low, in vitro production of interleukin-2 and of IgM was absent, and natural killer activity was decreased. The possibility that association of the CNS lesions, GH deficiency and immune defects could be due to alterations of the neuro-immuno-endocrine network secondary to a disturbance of neurotransmitters induced by precocious CNS damage of a viral or ischemic nature is discussed. PMID- 1519320 TI - Testosterone binding sites in the rat thymus during late embryonal and postnatal period. AB - Using immunoperoxidase staining with anti-testosterone Ab, has been shown that the cells binding testosterone were present in the rat thymus and that these cells are localized in the outer thymic cortex as well as in cortico-medullary region and medulla. Immunoperoxidase staining with that Ab at electron microscopy level showed that thymocytes as well as thymic epithelial cells bind this hormone. Combined immunoperoxidase staining with anti-testosterone Ab and immunofluorescence method with mAbs specific for thymocytes or thymic epithelial cells, revealed that thymocytes binding this hormone are localized mainly in the outer cortex, while thymic epithelial cells binding testosterone were found in cortico-medullary region and medulla. These testosterone binding cells were found, for the first time, in the thymus of 18-day-old fetus. It has also been shown that their density increased markedly by the day 3 of postnatal life and continued to increase up to the adult stage of organ development. These results indicate that testosterone can influence upon function of specific thymic epithelial cells, localized in the corticomedullary region and medulla. Thus, the results also suggest that this hormone can modulate T cell proliferation and/or differentiation, not only directly acting on the T cells localized in the outer thymic cortex, but also indirectly modulating function of the thymic epithelial cells that bind this hormone. PMID- 1519321 TI - Dexamethasone and hydrocortisone enhance the in vitro migration of prethymic stem cells to thymus supernatant. AB - The migration of prethymic stem cells from the bone marrow to thymus supernatant was examined in a blind well migration assay following treatment with glucocorticoids (GCS). To study the in vivo effects of GCS, time release pellets containing dexamethasone (DEX) were implanted subcutaneously in young adult CBA/J mice for 7, 14 and 21 days. After seven and 21 days of DEX treatment, enhanced migration of bone marrow lymphoid cells to thymus supernatant occurred. To study the in vitro effects of GCS on prethymic stem cell migration, bone marrow cells were incubated for one or six hours in media containing dexamethasone (DEX), hydrocortisone (HCS), or medium alone. After a six-hour incubation with GCS, significantly more bone marrow cells migrated toward thymus supernatant in vitro than bone marrow cells incubated in medium alone. The enhanced migration of cells to thymus supernatant seen in this assay may reflect a feedback mechanism whereby bone marrow cell migration is enhanced to restore the thymic lymphocyte reserves depleted following treatment with GCS. PMID- 1519322 TI - Yersinia enterocolitica and white cell filtration. PMID- 1519323 TI - A report of 104 transfusion errors in New York State. AB - In New York State, significant incidents involving the collection, processing, or transfusion of blood must be reported. Incident reports received over a 22-month period involving transfusion of blood to other than the intended recipient or release of blood of an incorrect group were analyzed. Among 1,784,600 transfusions of red cell components; there were 92 cases of erroneous transfusion that met study criteria (1/19,000). There were 54 ABO-incompatible transfusions (1/33,000); three of these (1/600,000) were fatal. Correction for underreporting of ABO-compatible errors resulted in an estimate of 1 per 12,000 as the true risk of transfusion error. National application of New York State data results in an estimate of 800 to 900 projected red cell-associated errors in the United States annually. The majority of reported errors occurred outside of the blood bank (43% resulted solely from failure to identify the patient and/or unit prior to transfusion and 11% resulted from phlebotomist error), while the blood bank was responsible for 25 percent of errors and contributed, with another hospital service, to 17 percent. The risk of transfusion of ABO-incompatible blood remains significant, and additional precautions to minimize the likelihood of such events should be considered. PMID- 1519324 TI - In vitro storage and in vivo survival studies of red cells from persons with the In(Lu) gene. AB - Red cells (RBCs) of individuals with the In(Lu) gene are characterized by suppression of the Lutheran, P1, i, and other blood group antigens, acanthocytosis, and abnormal electrolyte metabolism. To determine the clinical significance of these abnormalities, the survival of autologous RBCs was determined by 51Cr in two siblings with the dominant Lu(a-b-) [In(Lu)] phenotype. Both subjects studied had normal hemoglobin, hematocrit, reticulocyte count, haptoglobin, and ferritin values. RBC indices were mildly hypochromic. Examination of the peripheral smear showed mild acanthocytosis in one individual. Analysis of RBC distribution on discontinuous density gradients showed a shift to lighter fractions than normal control RBCs. Storage of these Lu (a-b-) RBCs at 4 degrees C showed significant hemolysis within a few days; this was confirmed by increased autohemolysis, which was reduced by glucose and ATP. RBC cation content (sodium and potassium) was higher than that in control cells, which indicated increased cell hydration, which explains the lighter density and mild hypochromia of the Lu(a-b-) RBCs. 51Cr survival of autologous Lu(a-b-) RBCs was normal in both subjects studied. The data indicate that the morphologic and cation abnormalities of RBCs of persons with the In(Lu) gene are clinically insignificant, as these cells have normal in vivo survival. Such RBCs, however, are susceptible to increased hemolysis in vitro under standard blood banking storage conditions. Individuals of the Lu(a-b-) phenotype, associated with In(Lu), may not be suitable candidates for routine blood donation. PMID- 1519325 TI - The binding of human alloantibodies to recombinant glycophorin A. AB - Chinese hamster ovary (CHO) cells were transfected with the wild-type, M allele of glycophorin A cDNA. The binding of human alloantibodies to recombinant glycophorin A was assessed with a modified hemagglutination-inhibition assay. Patient sera were incubated with acetone powders derived from CHO cells, and the adsorbed supernatants were tested in standard hemagglutination assays. Five M antibodies and one sample containing anti-En(a) bound to transfected CHO cells expressing glycophorin A but did not bind to untransfected CHO cells. Three N antibodies as well as 21 other alloantibodies (representing other major red cell blood group specificities) bound to neither CHO cell line. The M allele specificity of recombinant glycophorin A was further verified by the demonstration that a high-titer D alloantibody maintained the same titer of agglutination after incubation with recombinant glycophorin A. Transfected CHO cells thus express an M blood group antigen that appears to be serologically equivalent to that found on human red cells. A panel of cell lines expressing mutant glycophorin A molecules with defined variations in amino acid sequence and carbohydrate composition will be useful in studies of the fine specificity of human glycophorin alloantibodies. This approach may also provide an abundant source of artificial antigens for clinical use in blood group serology. PMID- 1519326 TI - Selection of platelets for refractory patients by HLA matching and prospective crossmatching. AB - A multi-site clinical study compared platelets chosen for refractory patients by prospective platelet crossmatching using stored donor platelets and HLA-based selection. Seventy-three patients who were refractory to random-donor platelets received two plateletpheresis components, one chosen by HLA-based criteria and the other by crossmatching. Patients were carefully evaluated to exclude nonimmune factors that could adversely affect transfusion results. Each of the five study sites used a crossmatch procedure with which it had experience. Results from this study indicate the following: 1) The overall rate of successful transfusion was similar when an HLA-based method of donor selection that includes all grades of matching and mismatching was compared to a crossmatch-based method of donor selection. 2) HLA-based selection that restricts recipients to grade A and BU matches was superior to a selection method based upon crossmatching alone. Donor selection based on HLA matching (grades A or BU) was also superior to selection based on any degree of HLA mismatching (grades BX, C, or D). 3) Selection of donors based on HLA-cross-reactive groups (defined by in vitro serologic crossreactivity) was no more successful than that based on grade C and D mismatches and was no more successful than selection by crossmatching alone. 4) Lymphocytotoxic and platelet antibodies were not detected in many of the enrolled patients, even though patients demonstrating nonimmune factors were eliminated from the study. It can be concluded that HLA-compatible (grades A and BU) platelets provide optimal support for refractory patients, but that crossmatch selected platelets are acceptable as an alternative component. PMID- 1519327 TI - Identifying elective orthopedic surgical patients transfused with amounts of blood in excess of need: the transfusion trigger revisited. AB - The discharge hematocrit has been analyzed as a clinical indicator of the transfusion trigger by which to identify patients undergoing elective orthopedic surgery who were transfused with blood in excess of need. The volume of red cells lost by each patient during surgical hospitalization was compared to the volume of red cells transfused. Three clinical indicator levels were considered. Red cell losses of 10, 20, and 30 percent of each patient's baseline red cell volume at admission were considered to be appropriate before subsequent blood transfusion replacement, representing generous, intermediate, or strict clinical indicator levels, respectively. With Level I as a generous clinical indicator, 110 (25%) of 525 patients were transfused in excess of blood needs; by Level II (intermediate) and Level III (strict) criteria, 221 (42%) and 314 (60%) of 525 patients, respectively, were transfused in excess of blood needs. Significant differences were found for transfused patients analyzed by gender (26% of women vs. 13% of men; Level I, p less than 0.001) and preoperative autologous blood donation (25% of autologous blood donors vs. 11% of those who did not donate autologous blood; Level I, p less than 0.001). It can be concluded that the discharge hematocrit and amount of blood lost during hospitalization can be used as clinical indicators with which to identify patients receiving transfusions in excess of needs in the elective surgical setting. With this method, it was found that the transfusion trigger is different for women and for men as well as for autologous blood donors and those who did not donate autologous blood undergoing elective orthopedic surgery [corrected]. PMID- 1519328 TI - The role of white cells in the transmission of Yersinia enterocolitica in blood components. AB - The mechanism for the transmission of Yersinia enterocolitica in blood components has been studied experimentally. One hypothesis is that, during a Yersinia infection in the blood donor, bacteria are phagocytosed by white cells (WBCs), but are not killed. After collection of blood from such a donor and component production, the bacteria are present in WBCs for some time, during which the unit appears sterile. Later, when the WBCs disintegrate, the bacteria are released and multiply in the unit. Aliquots of whole blood and buffy coat were inoculated with 100 colony-forming units (CFU) per mL of a Y. enterocolitica strain of type O:3 and left at room temperature for 5 hours. Some aliquots were then WBC-reduced by filtration, while others retained their WBC contents. All aliquots were kept at 4 degrees C for 6 weeks. Meat extract broth culture medium was used as a control. Growth in the range of 2000 CFU per mL was obtained in the broth control by 24 hours, whereas the whole blood and buffy coat units appeared sterile for the first days of storage. After 1 week, a trace of bacteria and, after 4 weeks, massive growth were found in the WBC-containing units but not in the WBC-reduced units. The likely explanation is that the bacteria had been phagocytosed by the WBCs and were thereby hidden and not available for bacterial culture during the first phase of storage. When the WBCs spontaneously disintegrated, bacteria were released and multiplied in the blood units.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1519329 TI - Prevention of growth of Yersinia enterocolitica in blood by polyester fiber filtration. AB - The ability of polyester white cell-reduction blood filters to prevent the growth of Yersinia enterocolitica in units of donated blood was studied. Sixteen units of freshly drawn blood were inoculated with 10, 50, 100, or 150 colony-forming units (CFU) per mL of a clinical isolate of Y. enterocolitica (serotype O:3). The units were subsequently fractionated into red cell concentrate and resuspended in AS-1 or AS-3 solution. One-half of the red cell concentrates in each solution were filtered within 15 hours of phlebotomy and stored for 42 days. The remaining units served as unfiltered controls. Bacterial growth was monitored by weekly cultures and, on the last storage day, by the presence of endotoxin and the formation of methemoglobin. One hundred twelve primary cultures (560 plates) were performed. Units collected in AS-1 and filtered remained sterile when initially inoculated with 50 CFU or less. Filtered units spiked with 100 CFU or less and collected in AS-3 remained sterile throughout their shelf life. All unfiltered units supported bacterial growth and the formation of endotoxin and methemoglobin. The filtration of freshly donated blood proves to limit the growth of Y. enterocolitica in red cell components. PMID- 1519330 TI - Removal of Yersinia enterocolitica from AS-1 red cells. AB - The growth of Yersinia enterocolitica in AS-1 red cells was investigated so as to study the organism's proliferation kinetics and to evaluate the effect of prestorage white cell (WBC) reduction on bacterial multiplication. Twenty-four 2 unit pools of ABO-compatible whole blood were prepared and inoculated with Y. enterocolitica to final concentrations ranging from 0.3 to 132 organisms per mL. After inoculation, pools were split equally, AS-1 red cells were prepared, and 1 unit of each pair (test unit) was WBC-reduced with a WBC-reduction filter. Quantitative bacterial cultures of both WBC-reduced and control units were performed at several points throughout preparation and storage. Less than 10 percent of the inoculated organisms was recovered from blood samples taken after a 7-hour room-temperature holding period. By the end of 42 days of storage, Y. enterocolitica was recovered from unfiltered red cells in 2 of the 6 units inoculated at the lowest levels (0.3 and 0.7 organism/mL), from 8 of the 12 units inoculated at the intermediate levels (2.8, 5.2, 30.7, and 43 organisms/mL) and from 6 of the 6 units inoculated at the highest levels (98.8 and 132 organisms/mL). Positive cultures were seen as early as Day 7. In contrast, filtered units inoculated at all levels less than or equal to 98.8 organisms per mL (21/21 units) were sterile at the end of the 42-day storage period, while 2 units (2/3) inoculated at 132 organisms per mL showed growth despite filtration.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1519331 TI - Growth of Yersinia species in artificially contaminated blood bags. AB - Transfusion blood bags were inoculated with less than 0.1 colony-forming units (CFU) of Yersinia enterocolitica (serotypes O:3, O:5, and O:9) and Yersinia pseudotuberculosis I per mL and stored at 4 degrees C for 41 days. During storage, samples were collected periodically and colony counts of serial dilutions were performed by plating on tryptic soy agar. After a lag-phase, the growth of Yersinia species from less than 0.1 CFU per mL to 10(9) CFU per mL was observed in 3 of 10 bags. The data showed that prolonged storage of contaminated blood bags allows Y. enterocolitica and Y. pseudotuberculosis to multiply to high levels. PMID- 1519332 TI - Blood group terminology suitable for use in electronic data processing equipment. PMID- 1519333 TI - White cell reduction, ultraviolet irradiation, and platelet refractoriness in acute myeloid leukemia. PMID- 1519334 TI - Autologous blood donation in "high-risk" patients. PMID- 1519335 TI - The first example of the McLeod phenotype in a Japanese baby with chronic granulomatous disease. PMID- 1519336 TI - Risk of transfusion-associated graft-versus-host disease as a result of directed donations from relatives. PMID- 1519337 TI - [Heat inactivation of tissue thromboplastin]. AB - Molecular mechanism of thermal inactivation of thromboplastin from the human brain using 1H, 31P-NMR has been studied. It was concluded that heating causes denaturation of protein moiety, disturbs hexagonal (H11) form of packing, immobilizes the lipids and decreases the mobility of their molecular segments. The dynamic properties of lipids become more homogeneous. PMID- 1519338 TI - [Protein synthesis during acclimation of cold-blooded animals to various temperatures]. AB - It was shown that the intensity of protein synthesis in cells of frogs, acclimated to 5 degrees C, is maintained at a high level, which is only 1.5-2 folds lower than that in animals acclimated to 20 C. In the process of acclimation to cold the intensity of synthesis decreases rapidly and already after 5 hours comprises one half of the value, which is characteristic of "warm" frogs, and the intensity of the process decreases more rapidly than the temperature of organs. On acclimation to warmth the intensity of protein synthesis increases and is getting stabilized at the level, characteristic of "warm" amphibia in 10-15 hours. It was shown that under various temperature conditions or conditions of acclimation specific proteins were synthesized against a background of the main groups of proteins. PMID- 1519339 TI - [Isolation and various properties of alpha-aminocaprolactam hydrolase from Klebsiella aerogenes]. AB - L-alpha-aminocaprolactam hydrolase possessing the L lysine amidase activity was isolated from Klebsiella aerogenes and purified. The procedure of enzymes purification included cell destruction on USDN-I, fractionation by ammonium sulfate, gel chromatography on G-200. The preparation of the purified enzyme possessed specific activity of 50 mumol of lysin per 1 mg of protein per hour. Km was 2.6 mM in case of phosphate buffer (ph 7.2) for I-alpha-aminocaprolactam. Besides L-alpha-aminocaprolactam the enzyme hydrolyses lysine amide, leucine amide tryptophanamide. Magnesium ions are necessary for manifestation of catalytic activity of the enzyme. PMID- 1519340 TI - [Antiradical properties and antioxidant activity of ecdysterone]. AB - Antiradical properties and total antioxidative activity of ecdysterone (10(-6) 10(-3)M were found on the model systems--photochemical one and that containing phosphatidylcholine liposomes oxidated with Fe2+ and Fe3+. The antioxidative activity of ecdysterone was shown to be comparable with that of the known inhibitors of peroxide oxidation of lipids--diethylparaphenylendiamine and ethylendiamine tetraacetate. PMID- 1519341 TI - Effect of androsole acetate on blood pressure of stress-sensitive hypertensive rats. AB - The basal and stress-induced blood pressure was found to decrease in rats with inherited stress sensitive hypertension (SSHR) followed by androzole acetate administration orally (30 mg/kg body weight) for eight days. The basal levels of arterial blood pressure was decreased by 17.5% and that of stress-induced animals -by 19%. PMID- 1519342 TI - [Modulating effect of surfactant on protein biosynthesis in lung macrophages]. AB - Effect of lung surfactant on protein biosynthesis in macrophages at their cultivation in vitro has been studied. The surfactant is shown to stimulate protein synthesis in the cells. This phenomenon is probably stipulated by the increase of the transcription activity and formation of 45-pre rRNA, life of RNA. The surfactant is supposed to regulate the function of lung macrophages in norm and under pathology. PMID- 1519343 TI - [Analysis of hepatocyte cell membrane antigens in regenerating rat liver]. AB - Antigens of plasma membranes in hepatocytes from regenerating rat liver were studied. Immunochemical investigation with polyvalent rabbits antiserum against plasma membrane proteins in hepatocytes from regenerating and normal rat liver have shown that liver regeneration processes are accompanied by the increase of proteins number with molecular weight of--80 kDa, 62 kDa, 40 kDa and 27 kDa. It is not excluded that protein with molecular weight of 27 kDa is the tissue specific peripheral protein. The influence of antibodies against proteins of hepatocytes plasmatic membranes on histostructure of pathologically changed liver tissue has been studied. The data obtained testify to a possibility of participation of the above mentioned proteins in the regulation of rat liver regeneration processes. PMID- 1519344 TI - [Stimulation of replicative DNA synthesis by eukaryotic proteins bound to single stranded DNA]. AB - The paper deals with the effect of the single-strand (ss) DNA-binding proteins (SSB-proteins) from the Ehrlich ascites tumor (EAT) cells and from the eggs of silkworm, as well as the mouse serum blood proteins, having preferential affinity to ss DNA, on the DNA replicative synthesis in the EAT cells permeable for the macromolecules, and, for the silkworm proteins and on the DNA replicative synthesis in the nuclei from the eggs of silkworm proteins and on the DNA replicative synthesis in the nuclei from the eggs of silkworm permeable for macromolecules. SSB-proteins of EAT to considerable extent stimulated the DNA synthesis. At the same time, the other proteins (from the silkworm and from the serum) activated the DNA synthesis in the permeable cells to the less extent. It was found that SSB-proteins from the silkworm had a 1.5-13 fold stimulating effect on the DNA replicative synthesis in the homologous system (in the permeable nuclei). If the permeability for the macromolecules of the cells and nuclei treatment with Triton X-100 may be different, it is supposed that the activation of the DNA synthesis by the exogenous proteins depends on the homologous system of the DNA replicative complex. It is possible that the effect of the serum proteins on the DNA synthesis is connected with the masking of the ss regions of DNA which inhibited DNA-polymerase alpha. Perhaps the mechanisms of the activation of the DNA replicative synthesis by the proteins in vitro with the purified DNA polymerase alpha and in vivo are of different nature and are conditioned by homology of the deoxyribonucleoproteins. PMID- 1519345 TI - [Study of the interaction of triethylenethiophosphamide with nucleotides by mass spectrometry with ionization by fission fragments of californium-252]. AB - Study of interaction of the antitumor alkylating drug triethylenethiophosphoramide (thioTEPA) with nucleotides (dGMP and dCMP) suggests highly perspective employment of 252-Cf fission fragment induced desorption mass spectrometry (252-Cf PDMS) in biochemical pharmacology. Using the 252-Cf PDMS the molecular masses of the unstable, unvolatile, high-molecular substances of biological origin and the chemical adducts or complexes with drugs can be used to establish some structural-functional parameters of the above mentioned biomolecules and their derivatives in microvolumes of the incubation medium. The resulting data may be used for modelling chemotherapeutic processes of "drug biomolecule-target" type. Using 252-Cf PDMS the complexes (dGMP (thioTEPA) n), n = 1, 2, 3 and (dCMP (thioTEPA) n), n = 1, were obtained. Some quantitative parameters and stability of these complexes were studied. Binding of dGMP with drug in the presence of dCMP was shown preferential. The data are compatible with the predictions concerning the mechanism of the antitumor property of the thioTEPA which can be manifested in the impairment structure of DNA of the malignant cells. PMID- 1519346 TI - [Acid-base status of the blood and adenine nucleotide metabolism in ruminant erythrocytes during early post-natal development]. AB - It has been established that data of acid-base balance in cows' and newborn calves' blood closely correlate with physiological status of animals during their initial days of postnatal ontogenesis and depend on the peculiarities of metabolism in fetus and newborn organisms. Data on the acid-base balance in blood of newborn calves under diarrhea syndrome are discussed from the point of view of the influence of rehydration therapy and "Namacit" preparation on clinical status of animals. PMID- 1519347 TI - [Significance of adenylic acid catabolites for mouse thymus regeneration]. AB - The distribution of [8-14C]adenylic acid catabolites in mouse thymocytes in cortisone-resistant and total thymocyte population has been studied. The accumulation of labelled catabolites in a form of hypoxanthine was found preferentially in cortisone resistant thymocytes but not in total population. This accumulation considerably grows after incubation of cortisone resistant thymocytes with non-peptide mitogenic factor. The excretion of labelled hypoxanthine into medium was also observed. In order to investigate a significance of hypoxanthine accumulation cortisone resistant thymocytes were incubated in the presence of hypoxanthine range concentration and [14C]thymidine incorporation into thymocyte DNA was determined. It was found that [14C]thymidine incorporation into thymocyte DNA increases after incubation in presence of 0.5 5.0 micrograms of hypoxanthine or 0.0005-5.0 micrograms of uric acid. It has been concluded that stimulation of [14C]thymidine incorporation and thymocyte proliferation by non-peptide mitogenic factor is caused by hypoxanthine accumulation. PMID- 1519348 TI - [Enzymatic activity of chymopsin of various origin]. AB - A number of enzymatic properties of fish pylochymopsin and bull chymopsin have been studied. Hydrolysis of synthetic ethers of N-benzoyl-L-tyrosine and N benzoyl-L-arginine by these chymopsins depending at the time and concentration of preparations has been studied. It was found that bull chymopsin is the most active one. It was shown that concentrations of 2 to 6 micrograms/ml of bull chymopsin and of 15 to 20 micrograms/ml of fish enzyme were optimal for synthetic substrate BTME hydrolysis. The significant trypsin activity was revealed in the both preparations on a number of synthetic amides. In contrast to the bull chymopsin the treatment of fish pylochymopsin by TPCK did not completely remove the chymotryptic activity of pylochymopsin. It was shown that tryptic activity in the both preparations was completely removed with TLCK. The time and concentration dependence of the autolysis in both chymopsins has been studied. It should be noted that this process is negligible for fish pylochymopsin in contrast to bull chymopsin. Stabilization of both proteases in aqueous solution at room temperature has been studied. Stabilization of the chymopsins in solution is achieved by the addition of various protein preparations including casein and serum albumin. The degree of stabilization by these proteins was achieved at 2% concentration. PMID- 1519349 TI - [Study of immobilization and properties of urease for creation of a biosensor based on semiconductor structures]. AB - Many-sided investigations of urease immobilization methods were carried out to create the biosensor devices on the base of semiconductor structures. Special attention was concentrated on the biomembrane formation by means of urease and bovine serum albumin (BSA) cross-linking by gaseous glutaraldehyde. Optimal conditions for the formation process were selected which preserve about 20% of total urease activity after the cross-linking. The properties of enzyme immobilized by the above-mentioned method have been comprehensively studied. They included the urease activity dependence on pH, ionic strength, incubation buffer capacity as well as the enzyme stability during its functioning, storing and thermoinactivation. As was shown, for immobilized ureas Km value for urea at pH 7.0 and 20 degrees C is 1.65 time less than for free enzyme. In the presence of EDTA (1 mM) the enzyme activity in the biomembrane is practically unchanged under a month storing. Biomembrane possesses good adhesion to silicon surface and its swelling level under different conditions does not exceed 35%. The conclusion is made about the prospects of the used method of biomembrane formation for biosensor technology based on semiconductor structures. PMID- 1519350 TI - [Kinetic characteristics of creatine kinase and hexokinase from rat skeletal muscles during dietary deficit of vitamin K and administration of pelentane]. AB - Kinetic parameters of rat creatine kinase isozymes at different vitamin K supply and treatment with antivitamin K--pelentan have been determined. MM-isozyme (skeletal muscle) has selective sensitivity to the vitamin K deficit, while BB and MB-isozymes (brain, kidney and heart) have not. The value KM for ATP of MM isozymes increases, while maximal activity decreases. Pelentan treatment does not lead to the change of MM-creatine kinase affinity to ATP. Soluble hexokinase of skeletal muscle in rats with vitamin K deficiency and treated with pelentan has higher affinity to glucose as compared to normal rat enzyme. It has been supposed that skeletal muscle hexokinase exists in a particular molecular form under vitamin K deficiency. PMID- 1519351 TI - [The role of transaminases in realizing the protective effect of L-aspartate in hypoxia]. AB - Activation of aspartate aminotransferase and alanine aminotransferase of mitochondria introduced to the incubation medium of pyridoxal-5'-phosphate (40 microM) is approximately 2 times higher than that of the corresponding cytoplasmic forms. At hypoxia aspartate aminotransferase activity in mitochondria and postmitochondrial supernatant tends to an increase while that of alanine aminotransferase decreases (above 2 times). The protection from hypoxic damage when using L-aspartate (100 mg/kg subcutaneously 3-5 min before hypoxia) intensifies an adaptive increase of aspartate aminotransferase activity and removes a decrease of alanine aminotransferase activity. Under these conditions stimulating effect of pyridoxal-5'-phosphate on transaminases activity in vitro weakens. A simultaneous administration of vitamin-coenzyme complex (thiamine pyrophosphate, lipoate, sodium 4-phospho-pantothenate, flavin-mononucleotide, nicotinate) intensifies these metabolic shifts and protective action of L aspartate. PMID- 1519352 TI - [Passive Ca2+ influx into vesicles of the sarcoplasmic reticulum, modified by succinic anhydride]. AB - Treatment of the sarcoplasmic reticulum (SR) vesicles with succinic anhydride in concentration of 1-2 mM modifies about 20% of amino groups. It increases initial rate and changes the pH-dependence of the passive influx of Ca2+ into vesicles and does not affect either Ca(2+)-binding or maximal passive Ca(2+)-loading of the SR vesicles. It is supposed that this effect may be caused by modification of the Ca-channel gating behaviour as a result of replacement of positive surface amino groups by carboxyl groups. PMID- 1519353 TI - [Peroxide modification of membranes and isomorphic composition of cytochrome P 450 of rat liver microsomes during antioxidant deficiency]. AB - Lipid peroxidation (LPO), physico-chemical properties of the membranes and isoformic composition of microsomal cytochrome P-450 from the rat liver were studied under conditions of antioxidant insufficiency (AOI) which was modelled by exclusion of alpha-tocopherol from the animals' ration. An insignificant accumulation of microsomal diene conjugates and schiff bases against a sharp increase of the ability to the prooxidant stimulated LPO in vitro took place. A significant decrease of membrane lipid microviscosity and a change in surface properties of microsomal membranes of rats with AOI was determined. Absence of alpha-tocopherol in the ration was accompanied by a significant change in the content of separate isoforms of cytochrome P-450 exhibited in growth of a polypeptide with m. w. 54 kDa and the lowering of proteins with m. w. 48 and 50 kDa. Less intensive quenching of tryptophan fluorescence by acrylamide was also revealed, which testified to a lower accessibility of the quencher to membrane proteins or their fluorophore sites. Modification of lipid composition and of physicochemical properties of the rat liver membrane microsomes which was observed at AOI was significantly correlated by pretreatment with the antioxidant 4-methyl-2,6-ditretbutylphenol (ionol). PMID- 1519354 TI - Molecular analysis of simian varicella virus DNA. AB - Clinical and pathological studies indicate that simian varicella virus (SVV) infection in primates is the counterpart of human varicella zoster virus (VZV) infection. The SVV and VZV genomes are also similar in size and structure. To extend studies of SVV DNA, we analyzed virus DNA from African green monkey kidney cells infected with the Delta-herpes-virus strain of SVV. The infectivity of SVV DNA was 88 PFU/micrograms. The buoyant density of SVV DNA, determined by isopycnic banding in CsCl gradients, was 1.700 +/- 0.002 g/ml, corresponding to a G + C molar ratio of 40.8%. The size of SVV DNA, estimated by analysis of restriction endonuclease digestion products and pulsed-field gel electrophoresis was 125.1 and 124.9 kbp, respectively. Electron microscopy of SVV DNA revealed a long region of 110.0 kbp, a unique short (Us) region of 5.1 kbp, and inverted repeat regions of 7.5 kbp flanking the Us. An EcoRI map of SVV DNA revealed two fragments not previously reported; our complete Pstl map also shows some differences. Mapping of SVV DNA with an additional restriction enzyme, measurement of full-length SVV DNA molecules, and the first use of pulsed-field electrophoresis to size SVV DNA, confirm and extend Gray's recent finding that SVV DNA has the same size and molecular configuration as VZV. We also show for the first time that the density of SVV DNA is similar to that of VZV DNA and that SVV DNA is infectious. PMID- 1519355 TI - Canine distemper virus increases procoagulant activity of macrophages. AB - Inflammatory demyelination in canine distemper has been proposed to be due to a "bystander" mechanism, in which macrophages play an important role. In the present work we studied whether infection of macrophages by canine distemper virus (CDV) results in changes of macrophage functions, including Fc receptor dependent and -independent phagocytosis, release of reactive oxygen species (ROS), and procoagulant activity (PCA). As a source of macrophages, dog bone marrow cells were seeded in teflon bags and grown for 1-2 weeks, at which time a marked enrichment of macrophages was noted. These cells were infected with the A75/17 strain of CDV. We could not detect any significant difference between uninfected and CDV-infected macrophages with respect to Fc receptor-dependent or independent phagocytosis or with respect to the release of ROS. However, from Day 4 p.i. to the end of our observation period (10 days p.i.), PCA was up to 10-fold higher in CDV-infected unstimulated macrophage cultures than in uninfected unstimulated cultures of the same age. Increase in PCA was not due to the inoculation procedure by itself nor to components of the inoculum other than CDV; in particular, PCA was not due to contaminating endotoxin. Thus, several important macrophage functions do not appear to be impaired by CDV infection. The marked increase of macrophage PCA expression suggests that certain macrophage functions may even be enhanced as a result of infection. Such macrophage activation might contribute to the pathogenesis of the disease. PMID- 1519356 TI - Bacteriophage phi 6 envelope elucidated by chemical cross-linking, immunodetection, and cryoelectron microscopy. AB - Bacteriophage phi 6 is an enveloped dsRNA virus which infects the plant pathogenic Pseudomonas syringae bacterium. Using low dose cryoelectron microscopy we show that the nucleocapsid, spikeless virion, and intact virion have radii of 29, 35, and 43 nm, respectively. Thus, the membrane is 6 nm thick and the surface spikes of the receptor binding protein P3 extend 8 nm from the membrane surface. Cross-linking, immunological, and complementation evidence suggest that the spikes are formed of multimeric P3 molecules and that P3 is associated with membrane-bound protein P6. We observe that the envelope can accommodate up to 400 molecules of P3 but that the average virion contains less than one-fourth of this amount. Assembly of a very small number of P3 or truncated P3 molecules onto inactive virions restores infectivity, showing that only a few spikes are necessary for receptor binding and membrane fusion. PMID- 1519357 TI - Ugandan HIV-1 V3 loop sequences closely related to the U.S./European consensus. AB - The third variable (V3) loop of the human immunodeficiency virus type 1 (HIV-1) envelope protein is an important determinant for virus neutralization and cell tropism. V3 loop sequences from uncultured lymphocytes obtained in 1990 from 22 Ugandan HIV-1-infected patients could, with the exception of two patients' sequences, be divided into two groups (A and B) on the basis the V3 loop size and sequence. The V3 loop consensus sequences from both groups showed a high degree of homology to a U.S./European consensus, a characteristic also reflected by the results of peptide serology. In the case of group B the difference in sequence was only five amino acids. In contrast, the V3-flanking regions for both groups showed greater homology to an earlier (1986/1987) Ugandan consensus. The discovery of these two new Ugandan V3 loop genotypes, which are closely related to the U.S./European consensus, has implications for the understanding of the evolution of HIV-1 and for the future design of a vaccine for use in Africa. PMID- 1519358 TI - Three regions of cauliflower mosaic virus strain W260 are involved in systemic infection of solanaceous hosts. AB - We have identified regions of CaMV strain W260 involved in systemic infection of Nicotiana bigelovii and Datura stramonium by constructing chimeric viruses between W260 and CM1841, a strain that is unable to systemically infect any solanaceous host. All of the chimeric viruses systemically infected turnips, demonstrating the viability of the chimeric viruses in a host that is susceptible to both CM1841 and W260. Three regions of W260, containing primarily genes I, IV, and VI, influenced the ability of that virus to induce systemic symptoms in the solanaceous hosts. The involvement of the regions containing gene I, and to a lesser extent gene IV, were affected by environmental conditions. When infected plants were grown under conditions of low light, low temperatures (18 degrees), and short days (9.5-hr day), the source of genes I and IV no longer influenced whether a chimeric virus moved systemically. As light intensity and day length were increased, the genetic requirements became more stringent and genes I and IV, as well as gene VI, had to be derived from W260. PMID- 1519359 TI - A synthetic early promoter from a baculovirus: roles of the TATA box and conserved start site CAGT sequence in basal levels of transcription. AB - Many baculovirus early genes and insect genes transcribed by RNA polymerase II have a conserved transcription start site sequence (CAGT) located downstream of a consensus TATA box. To examine the functions and interactions of these two motifs in initiating accurately positioned basal transcription, a 43-nt synthetic promoter was synthesized from the TATA box and start site sequences of the gp64 early promoter from the Orgyia pseudotsugata multicapsid nuclear polyhedrosis virus (OpMNPV). The synthetic promoter initiated accurately and was also transactivated by the baculovirus transcriptional activator, IE1. To determine the roles of sequences within the 43-nt synthetic promoter, a series of linker scanning and spacing mutations were analyzed for transcriptional activity, start site selection, and transactivation. Linker-scanning mutations were examined in vivo by transient expression and reporter gene assays. To examine transcription start site selection, promoter constructs were used for in vitro transcription in nuclear extracts from uninfected Spodoptera frugiperda (Sf9) cells. In vivo and in vitro analyses show that the TATA box, and not the start site CAGT, is the primary element controlling start site selection. Substitution of the conserved start site CAGT sequence resulted in a reduction of both reporter gene activity and in vitro transcripts, although transcripts initiated accurately. Data from linker-scanning and spacing mutations indicate that the conserved start site CAGT sequences are not required for accurate initiation but sequences at the start site play an important role in initiation efficiency. PMID- 1519360 TI - Sequence and analysis of the capsid protein of Nudaurelia capensis omega virus, an insect virus with T = 4 icosahedral symmetry. AB - We have determined the nucleotide sequence of the RNA2 segment of the Nudaurelia capensis omega virus genome. It was found to consist of 2448 nucleotides and contained one long open reading frame (ORF) encoding the 644 residue capsid protein. The deduced amino acid sequence of this protein reveals a positively charged amino terminus, a characteristic exhibited by several other viral capsid proteins, that is thought to be important for interactions between the capsid and the genomic RNA. There are 366 and 150 bases of untranslated sequence on the 5' and 3' ends, respectively. The ORF encoding the capsid protein initiates at the second AUG from the 5' end. The 5' proximal AUG specifies a short ORF (30 codons) which terminates 1 base before the initiation codon for the coat protein. Our analysis also revealed the presence of a second, previously unidentified polypeptide associated with Nudaurelia capensis omega virus particles. The amino terminal sequence of this protein corresponds to a portion of the long ORF beginning at codon 571. The lack of an initiation codon near this sequence indicates that the small polypeptide is most likely produced as a carboxy terminal cleavage product from a 70-kDa capsid protein precursor, yielding the previously identified 62-kDa protein and the 8-kDa protein that we have observed. The putative cleavage site would be at an Asn/Phe pair, somewhat resembling known cleavage sites (Asn/Ala) in the T = 3 Nodaviridae. In addition, we have found that there is also a second polypeptide similar in size to that from Nudaurelia capensis omega virus associated with particles of Nudaurelia capensis beta virus, the type member of Tetraviridae. PMID- 1519361 TI - A cellular promoter-based expression cassette for generating recombinant baculoviruses directing rapid expression of passenger genes in infected insects. AB - We have developed an expression cassette which allows the generation of recombinant baculoviruses that can express passenger genes under the control of a constitutive cellular promoter derived from the cytoplasmic actin gene of the silkmoth Bombyx mori. Silkmoth tissue culture cells which were infected with a recombinant B. mori nuclear polyhedrosis virus (BmNPV) containing the gene encoding chloramphenicol acetyltransferase (CAT) under the control of this expression cassette expressed significant CAT activity beginning 5 hr postinfection (p.i.). Cells infected with a recombinant BmNPV containing the cat gene under the control of the polyhedrin gene promoter did not express CAT activity until 20 hr p.i. Silkworm larvae were also infected with the two recombinant viruses by hemocelic injections and all larval tissues examined were found to express the cat gene. While significant actin-cassette-driven CAT expression in vivo was first seen at 24 hr p.i., expression from the polyhedrin promoter was not seen until 48 hr p.i. By 60 hr p.i., tissues of larvae infected with the recombinant virus expressing cat under polyhedrin promoter control were found to exhibit sixfold higher CAT activity than those infected with recombinant virus expressing the cat gene under the control of the actin promoter. The 24-hr temporal advantage in expression of a passenger gene in infected larvae indicates that the actin-promoter-based expression cassette or other analogous cellular promoter-based cassettes could be used for generating recombinant baculovirus insecticides which could incapacitate pest insects more quickly than viruses employing the polyhedrin or other late viral promoters for expressing insect incapacitating proteins. PMID- 1519362 TI - Cloning and nucleotide sequence of the 5' part of v-myb cDNA. AB - cDNA of a subgenomic v-myb mRNA from AMV-transformed BM-2 cells was cloned. Sequencing of the 5' end of this cDNA revealed the structure of both AMV leader and the splice junction in v-myb message. The leader is a novel variant of known avian retrovirus leaders. The long open reading frame in the cloned cDNA starts with six gag-derived codons spliced to the myb-specific sequence. PMID- 1519363 TI - Effects of site-directed mutagenesis on the presumed catalytic triad and substrate-binding pocket of grapevine fanleaf nepovirus 24-kDa proteinase. AB - Grapevine fanleaf nepovirus (GFLV) has a bipartite plus-sense RNA genome. Its structural and functional proteins originate from polyprotein maturation by at least one virus-encoded proteinase. Here we describe the cloning of the 24-kDa proteinase cistron located between the virus-linked protein (VPg) and the RNA dependent RNA polymerase cistron in GFLV RNA1 (nucleotides 3966 to 4622). Proteinase expressed from this clone is able to cleave GFLV polyprotein P2 in order to produce the coat protein and a 66-kDa protein which is further processed to the 38-kDa presumed movement protein. The GFLV 24-kDa proteinase sequence contains sequence similarities with other nepovirus and comovirus proteinases, particularly at the level of the conserved domains corresponding to the hypothetical catalytic triad and to the substrate-binding pocket (amino acids 192 to 200). Site-directed mutagenesis of residues His43, Glu87, and Leu197 abolished proteinase activity. Inactivation of the enzyme is also observed if the catalytic residue Cys179 was substituted by isoleucine, but replacement by a serine at the same position produced a mutant with an activity identical to that of native proteinase. All our data show that GFLV cysteine proteinase presents structure similarities to the proteinases of cowpea mosaic virus and potyviruses but is most closely related to trypsin. PMID- 1519364 TI - Feasibility of a predeposit autologous blood donation program in colorectal cancer patients: results from a randomized clinical study. AB - The hematologic and transfusion data of a multicenter randomized trial investigating the effect of blood transfusions on the 5-year survival were used to study the feasibility of an autologous blood donation program in colorectal cancer patients. Three hundred and ten patients were randomized for autologous blood transfusions (predeposition of 2 units) or homologous blood transfusions, and transfusion rules were standardized. The Hb level in the patients who donated blood decreased by 20.1 +/- 1.3 g/l (mean +/- SEM) preoperatively and 4.5 +/- 1.8 g/l postoperatively, and in controls 3.7 +/- 1.1 g/l and 16.5 +/- 1.9 g/l (significantly different between the two groups, both pre- and postoperatively: p less than 0.01). Because blood loss and number of transfusions were similar in both groups, this indicated that either preoperative or postoperative erythropoiesis is stronger in patients who had donated blood. Twenty-three percent of the autologous patients and 61% of the homologous patients were exposed to homologous blood. The effectiveness of the procedure differed per tumor localization. In patients with a right-sided colon carcinoma, 22% of the control patients needed homologous blood, compared to 10% of the autologous patients. In patients with other colon carcinomas, this was 52 and 16%, respectively, and in patients with a rectal carcinoma 85 and 41%. We conclude that predeposition of 2 units of blood for colorectal cancer surgery is feasible and useful to prevent homologous blood usage in a significant number of patients with left colon carcinoma or rectal carcinoma. PMID- 1519365 TI - A case of 'auto-immune thrombocytopenic purpura' serologically similar to post transfusion purpura. AB - The report describes a HPA-1a (Zwa)-negative woman with thrombocytopenia and antibodies in serum and eluate from autologous platelets with an operational anti HPA-1a specificity. The results of the serological investigations were similar to the findings in most patients suffering from post-transfusion purpura. However, the present patient had no history of blood transfusion prior to the unset of purpura and the thrombocytopenia had persisted 6 months before splenectomy. PMID- 1519366 TI - Quantitation of the human component C4: definition of C4 Q0 alleles and C4A duplications. AB - We determined the C4 plasma concentrations of 48 genotypically CA4- and C4B defined unrelated individuals from 34 families with a total of 196 members by an enzyme-linked immunosorbent assay using Rg:1,2 (C4A) and Ch:1 (C4B) specific monoclonal antibodies. The results obtained allowed the establishment of rules for the detection of C4 Q0 alleles in the heterozygous form and of C4A gene duplications. In the present study seven homoduplications of the C4A 3 allotype were defined which had not been detected by allotyping. This procedure allows the simple, reliable, and quick determination of Rg:1,2 and Ch:1 plasma levels which are not influenced by daily rhythms of C4 production. PMID- 1519367 TI - Haemolytic disease of the newborn due to anti-Dia and incidence of the Dia antigen in Poland. AB - A strong complement-fixing incomplete anti-Dia was found in the serum of a Polish mother who gave birth to a newborn suffering from a severe haemolytic anaemia. The whole family was of Polish origin. 9,661 donor blood samples from different regions of Poland were tested against antiserum derived from that mother. Dia antigen was present on red cells of 45 (0.46%) individuals. All of them were of Polish origin. In some cases, family studies were undertaken. PMID- 1519368 TI - Gm typing, IgG subclasses of anti-Rh(D) and severity of hemolytic disease of the newborn. PMID- 1519369 TI - Aluminum content of source plasma and sodium citrate anticoagulant. AB - The concentration of aluminum was determined in samples of source plasma collected by the normal plasmapheresis procedure, which involves collection in anticoagulant and immediate freezing. Samples of sodium citrate anticoagulant used in the collection of source plasma were also tested for aluminum, as were empty source plasma containers and 0.9% sodium chloride infusion (USP). Samples of source plasma were collected from a geographic cross-section of the donor population in the USA by three different manufacturers. Aliquots of these samples were mixed with Triton X-100 and sulfuric acid and analyzed for aluminum by atomic absorption spectrometry using electrothermal atomization (graphite furnace) and Zeeman background correction. The arithmetic mean and standard deviation for the aluminum content of 28 samples of source plasma were found to be 25.5 +/- 8.4 ng Al/ml. The aluminum content of the individual samples of source plasma ranged from 12 to 48 ng Al/ml. The aluminum content of 6 samples from two manufacturers of the sodium citrate anticoagulant that is used in source plasma ranged from 410 to 2,080 ng/ml. Aluminum levels found in saline for infusion and nitric acid leachates from empty source plasma containers were less than 6.9 ng/ml. The level of aluminum expected in uncontaminated human blood has been estimated to be 10 ng Al/ml or less. Comparison of this figure with the present data indicates that the sodium citrate anticoagulant contributes significantly to the aluminum load of source plasma and, therefore, to the aluminum content of products such as albumin derived from source plasma. PMID- 1519370 TI - pH, temperature and lactate production in human red blood cells: implications for blood storage and glycolytic control. AB - The interaction of temperature and pH in biological systems comprises two components. Temperature change may perturb the pH of solutions, and it may change the pKa of some ionizable groups that are involved in enzyme catalysis. The pH optima of single reactions and whole pathways are therefore temperature sensitive. The pH optimum of glycolysis in human red cells has been investigated only at 37 degrees C. We have measured the effect of temperature on the pH of stored blood suspensions and on the pH optimum of glycolysis in the human red cell. The pH of the cell suspensions in a traditional storage medium was 7.25 +/- 0.2 at 4 degrees C. The pH optimum of glycolysis was high (7.8-8.5) between 15 and 35 degrees C. It can be inferred from our data that human red cells are currently stored at least 0.5 pH units below the pH optimum of glycolysis at 4 degrees C. This suggestion is supported by storage experiments which showed that glycolysis at 4 degrees C was at least 1.5-fold more active at an initial pH of 7.67 versus 7.36. Equations which describe the variation in reaction velocity with pH were fitted to the pH curves for glycolysis in order to identify the ionizable groups that contribute to the effect of pH on glycolysis. It is generally accepted that hexokinase catalyses the rate-limiting step in glycolysis in the human red cell, but none of the ionizable groups implicated correspond to that involved in the hexokinase reaction. PMID- 1519371 TI - Comparison of five different filters for the removal of leukocytes from red cell concentrates. AB - The leukocyte depletion capacity and performance of 5 filters designed for filtration of red cell concentrates (RCC) were compared by counting leukocytes, measuring red cell volumes and by histological examination of the filters after use. To eliminate interdonor differences, 5 buffy-coat-poor RCC were pooled (in each of 10 experiments) and subsequently split up into the original bags. The RCC were passed over the Cellselect filter, a column filled with cellulose acetate, and over flat-bed polyester filters: the Cellselect Optima, the Pall RC 50, the Leukostop and the Sepacell R-500. The filtration was shortest with the Pall RC 50 (p less than 0.001 compared to the other 4 filters). Leukocyte removal was most effective with the cellulose acetate filter (p less than 0.01 compared to the other 4 filters) followed by the Cellselect Optima polyester filter (p less than 0.02 compared to the remaining 3 filters). Residual leukocytes did not exceed 50 x 10(6) for any brand of filter. Red cell recovery was similar for all 5 filters with mean values from 86.1 to 89.2%. The leukocyte numbers, counted in Turk's solution or in propidium iodide, gave comparable values in hemocytometers applying light microscopy or fluorescent microscopy, respectively. Histological examination showed that lymphocytes were mainly removed by trapping, whereas granulocytes showed a variable pattern: adhesion in presence of platelets or trapping. PMID- 1519372 TI - Platelet concentrates stored in synthetic medium after filtration. AB - Platelet concentrates prepared from pooled buffy coats (BCPC) were stored in Plasma-Lyte A, a glucose-free synthetic medium, after leukocyte depletion by filtration through Pall PL 50, and compared to paired unfiltered BCPC stored in the same medium. Each pair of BCPC units was prepared from a pool of 10 buffy coats split into two identical units. Platelet and leukocyte counts per unit of BCPC were 2.70 +/- 0.19 x 10(11) and 3.8 +/- 2.8 x 10(6) (filtered BCPC), 2.59 +/ 0.27 x 10(11) and 79 +/- 56 x 10(6) (control BCPC), respectively. Filtration procedures did not affect in vitro parameters of platelet quality and function such as osmotic reversal, ATP release and aggregation in response to collagen and ADP during 15-day storage. A similar decrease of platelet membrane glycoprotein Ib and a similar rise of activation markers GMP-140, gp 53 and platelet-bound fibrinogen were observed during storage of filtered and control BCPC. Our study indicates that storage of BCPC after filtration is feasible and that a reduction in leukocyte content by filtration to mean cell counts of less than five millions per unit has probably no effect on platelet storage lesion. PMID- 1519373 TI - First autoclave-sterilized platelet-additive solution containing glucose with a physiological pH for the preparation of plasma-poor platelet concentrates. AB - The glucose-free platelet-additive solution (termed AR solution), developed by Adams and Rock [Transfusion 1988;28:217-220], was modified by adding glucose as an energy substrate for platelets and maltose to prevent platelet lysis and by replacing sodium gluconate with sodium phosphate for better pH maintenance. The new platelet-additive solution (termed Seto solution) contained 90 mM NaCl, 5 mM KCl, 3 mM MgCl2, 17 mM tri-sodium citrate, 4.9 mM NaH2PO4, 20.1 mM Na2HPO4, 23 mM sodium acetate, 28.8 mM maltose, and 23.5 mM glucose with a pH of 7.4. The solution was sterilized by autoclaving in plastic bags in nitrogen to prevent glucose caramelization at high pH. Plasma-poor platelet concentrates prepared by adding Seto solution to the pelleted platelet buttons were stored in a LE-2 polyolefin bag at 22 degrees C with constant agitation for 5 days. The platelets suspended in Seto solution maintained oxygen consumption at a rate of 1.1 nmol/min/10(9) platelets after 5-day storage, with glucose consumption and lactate production rates of 0.5 +/- 0.2 and 1.2 +/- 0.2 nmol/min/10(9) platelets, respectively. This resulted in a final mean pH of 7.0. Those suspended in AR solution ceased glycolysis within 3 days because residual plasma glucose had been consumed. This was associated with decreases in percent hypotonic shock response and aggregation induced by adenosine diphosphate and collagen. Lactate dehydrogenase discharge in AR solution was 5 and 8 times higher at day 3 and day 5, respectively, than that of Seto solution. Morphologically, there were no ballooned platelets after storage in Seto solution.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1519375 TI - Euthanasia. AB - The principles of self-determination and individual well-being support the use of voluntary euthanasia by those who do not have moral or professional objections to it. Opponents of this posture cite the ethical wrongness of the act itself and the folly of any public or legal policy permitting euthanasia. Positive consequences of making euthanasia legally permissible respect the autonomy of competent patients desiring it, expand the population of patients who can choose the option, and release the dying patient from otherwise prolonged suffering and agony. Potentially bad consequences of permitting euthanasia include the undermining of the "moral center" of medicine by allowing physicians to kill, the weakening of society's commitment to provide optimal care for dying patients, and, of greatest concern, the "slippery slope" argument. The evaluation of the arguments leads to support for euthanasia, with its performance not incompatible with a physician's professional commitment. PMID- 1519376 TI - Nurse participation in decisions regarding limitation of treatment. AB - A vast literature exists on the ethical aspects of decisions to limit life sustaining treatments, and much of it deals with the way decisions ought to be made. Little is known, however, about how decisions are made in actual clinical practice. Empirical studies have not investigated the decision-making process directly and, with one exception, have only focused on physician practices. Through the use of a case, this paper examines the nature of hospital cancer nurses' involvement in the decision-making process. Three practice domains are identified: assisting patients to reach a truly autonomous choice, helping families to understand and to cope with the realities of the situation, and communicating with and encouraging open communication among all those involved. In addition, the potential value of the in-between position of the nurse is noted, and nurse responsibilities are summarized. PMID- 1519374 TI - Observations on ethical problems and terminal care. AB - Progress in medical diagnosis and therapy has raised new problems with far reaching ethical implications. Medicine must remain a profession and not become a business. Textbooks must address ethical problems in the context of health care decisions and not restrict themselves to pathophysiology and practical therapeutics alone. The relative roles of the principles of autonomy, non maleficence, beneficence, and justice must be balanced and appropriately applied to individual situations in biomedical ethics. When therapy becomes futile and the suffering of the patient does not justify any anticipated benefit, the patient (and/or patient surrogate) may request withholding or even withdrawing life-prolonging interventions. In the persistent vegetative state, even nutritional support by an unnatural (tube) route may ethically be denied at the patient's (or surrogate's) informed decision. New areas of ethical evaluation have been raised by the desire of some individuals to prolongation of their lives at high expense to the society such that other individuals are denied services because of limitation of available resources. There has been a long-standing conflict of interest between the acceptance by physicians and/or medical institutions of money or gifts from pharmaceutical companies whose drugs they prescribe, stock, or sell. This practice increases the cost of the drugs and is, in effect, a "sick tax," which is morally wrong. PMID- 1519377 TI - Spiritual aspects of death and dying. AB - Dying is an event beyond our comprehension, an experience that can only be imagined. Patients with cancer have a gift denied many others: some time to prepare for the approaching end of life. This time can be used to bring old conflicts to a close, to say goodbye and seek forgiveness from others, to express love and gratitude for the gifts of a life. Physicians can help patients by being aware of the spiritual dimensions to life that many patients have. In major religious traditions, death is accepted as the natural end of the gift of life and as a point of transition to another, yet unknown, existence. For many patients, it is not death that is feared, but abandonment. The physician's awareness of the spiritual needs of patients can make care of the dying more rewarding and fulfilling for all concerned. PMID- 1519378 TI - Clinical trials and physicians as double agents. AB - Inherent in the dual role of physician-researcher is a conflict of interest arising out of the competing objectives of research and medical practice. Most commentary and policy recommendations on this conflict of interest have focused on the problems that arise in negotiations for informed consent. These are not, however, the only problems presented by this conflict; they are not necessarily even the most important. In order to deal with these problems, several commentators have suggested various procedural safeguards to protect the interests of the patient-subject--for example, separating the roles of physician and researcher, or introducing third parties into the relationship in order to assist in the initial or continuing negotiations for informed consent. In my view, the necessity for special procedural protections of patient-subject interests should be a discretionary judgment of the Institutional Review Board (IRB). In determining the need for special procedural protections for any research protocol, the IRB should consider three factors. To the extent that any one of these or a combination of two or more seems to present a problem, the IRB should consider it increasingly important to recommend special procedural protections: 1. There are serious impairments of the prospective subjects' capacities to consent. 2. The risk of physical or psychological injury presented by procedures done in the interests of research exceeds the threshold of "a minor increment above minimal risk." 3. The protocol is designed to introduce, test, evaluate, or compare therapeutic, diagnostic, or prophylactic maneuvers. PMID- 1519379 TI - Rationing health care: its impact and implications for hematology-oncology. AB - Rationing of health care in the United States currently exists via the covert mechanism of restricting significant segments of medical care for many of those who cannot afford it. Provision of universal health care would necessitate explicit rationing of certain interventions and technologies, even though an individual could afford them. The British and Canadian experiences provide lessons from which America can profit, and the Oregon health plan is an experiment in this direction. The progressive "graying" of America has raised the question of the need for intergenerational charity as a form of rationing. The implications of these rationing plans would result in a major restructuring of the practice of hematology-oncology. PMID- 1519380 TI - Cancer therapy: reimbursement of new therapeutic technologies. AB - New drugs and technologies for cancer treatment are being developed at a rate that has created a reimbursement crisis. This article discusses third-party concerns about this problem and describes generic criteria that have proven to be useful in assessing any new technology. It is equally important to discontinue funding of ineffective and obsolete therapies as it is to devise a strategy for identifying and encouraging the development of new therapy that will be both clinically useful and cost-effective. Examples are provided to show that these are not necessarily mutually exclusive goals. Off-label application of standard therapy as well as the funding of new cancer therapy are considered. High-dose chemotherapy with autologous stem-cell support for treatment of a variety of neoplasms has become a major reimbursement challenge. Other technologies such as autolymphocyte therapy and use of colony-stimulating factors are considered in detail. Finally, a process for deciding how to fund new cancer therapy is described. PMID- 1519382 TI - [Social diagnosis: assessment scales and evaluation of "social adjustment" of psychiatric patients]. AB - For diagnostic and prognostic considerations, rehabilitation and outcome evaluation in patients with mental disorders it proved to be indispensable to diagnose not only psychopathology but also social impairment. This study gives a review about the different instruments assessing social adjustment, and their application in out- and inpatient settings. Part of the instruments are based on statements of relevant informants, whereas others are based on observable behaviour. Hints are given to expense, objectivity of assessment and repeated measurements. PMID- 1519381 TI - Childhood malignancies and decision making. AB - Failure to obtain "adequate" medical care for a child constitutes child neglect, which may be used as the basis for prosecution of parents, removal of the child from the home, or court-ordered medical treatment. "Adequate" care is usually construed as that which is given by a licensed physician, but, in case of dispute, courts almost never engage in choosing one medical approach over another. The principle that parents may not refuse medical care, however, is made very difficult when children have malignancies--the long-term nature of the treatment means that, if the child is left at home, court order or not, the parents may flee with their child. Removing the child from the home, however, adds that trauma to the ill child's burdens. Questions should be asked before making a request to a court to order a therapy which will prolong but not save a child's life if the parents would prefer to spare their child the side effects. Parents, however, may always refuse to permit their child to participate in research studies, no matter how promising. Adolescents are increasingly believed to be capable of medical decision making; most courts, however, would not allow an adolescent to refuse life-saving treatment. PMID- 1519383 TI - [Eugen Bleuler (1857-1939) and psychoanalysis]. AB - The relationship of Eugen Bleuler with psychoanalysis can be characterized as a history of overture and distance. In previous literature this relationship has been mainly studied from a historical and biographical point of view. In this article the authors review the history of Bleuler's attitude toward psychoanalysis from an ideengeschichtlich point of view. They distinguish and argue three periods. 1896-1906: the initial period was one of overt appreciation and positive rapprochement; 1906-1911: Bleulers initial positive attitude is more and more thwarted by fundamental theoretical disagreement and by his opposition against Freud's group building strategy; from 1912 on, Bleuler clearly dissociates himself from psychoanalytic theory and movement. An interpretation of this evolution is given in terms of personal and above all of theoretical incompatibility. PMID- 1519384 TI - [Experimentally-induced stress in dyadic interactions. Presentation of the EISI (experimentally-induced stress in dyadic interactions) experiment]. AB - In this article we present an experimental study (EISI-experiment: experimental induced stress in dyadic interaction), which focuses on a method for analysing individual and dyadic stress-experience and coping as well as its influence on dyadic interaction. The experiment offers a new diagnostic approach to analyse interaction processes under stress. We report the concept of our experimental design and show some first results. The findings suggest that our method is useful for the examination of stress phenomena in close relationships. It allows the investigation of interactional processes and in this context especially of "dyadic coping", a form of stress-management by couples. PMID- 1519385 TI - [Looking into the past. Psychological and gerontologic aspects of memory]. AB - Reminiscence is characterized by a dialectical relation of past and present which is of fundamental importance for personal identity. Moreover, it shows a double aspect, implying both the private recollection of one's past and the social dimension of narration, instruction and self-disclosure. This will be illustrated by a consideration of the different forms and functions of reminiscence in general, and by the results of research on the role of reminiscence in later life. An investigation into these aspects of reminiscence may also further a therapeutic approach to the crises resulting from unresolved conflicts in the life history. PMID- 1519386 TI - [Use of gestures to support speech comprehension of a hearing, nonverbal severely mentally handicapped adult with autistic behavior]. AB - In the present single case study the reactions of a severely mentally handicapped adult with autistic behaviour to simple instructions were investigated; in each case with and without gestural facilitation. This procedure was varied both with regard to persons and to situations. The correct following of requests as well as special behaviour such as uncertainty, smiling, delay of reactions and enthusiasm was registered and analysed by videotape. It could be clearly proved that the requests which were supported by gestures were more often performed correctly. On top of that it could be observed that under these circumstances the handicapped person was less uncertain, showed fewer stereotypies and was generally more interested. No influence could be noticed on the delay of reaction as well as on the person's enthusiasm. No difference could be seen between different persons and situations. Further research projects should particularly analyse how far the use of gestures does not only serve more communication but also has an influence on the range of behavioural disorders. PMID- 1519387 TI - [Heat-induced decomposition of disaccharide Amadori compounds in quasi-water-free reaction conditions]. AB - The thermally induced decomposition of disaccharide Amadori compounds has been compared to those of monosaccharide ones under almost water-free conditions. The structure of the synthesized maltulosyl compound has been proved to be 4C1-alpha D-glucopyranosyl- (1----4)-2C5-beta-D-fructopyranosylglycine by 1H- and 13C-NMR spectroscopy. The decomposition of Amadori compounds has been used to study the kinetics of the browning reaction. Compared to fructosylglycine and maltotriulosylglycine, the browning of the disaccharide is faster. Curie point pyrolysis at 300 degrees C and investigation of the pyrolysate by gas chromatography/mass spectrometry have shown that the disaccharide component influences the thermal process. Furanes and furanones have been detected as predominant degradation products, the main one being 2(5H)-furanone. For the first time, we suggest a reaction pathway for the formation of these products via the Maillard reaction which includes 1,6-anhydroglucose. PMID- 1519388 TI - Coeliac active peptides from gliadin: large-scale preparation and characterization. AB - Larger amounts of coeliac active peptides are required for pathogenetic investigations. Therefore, a simplified preparative procedure by means of gel permeation chromatography and reversed-phase HPLC was developed for the isolation of the peptides B3141-B3146, which are present in peptic tryptic digests of gliadin [this journal (1983) 176:85-94]. The peptides are derived from the N terminal part of alpha-gliadins and are closely related. The amino acid sequence of B3143 is VPVPQLQPQNPSQQQPQEQVPLVQQQQFPGQQQQFPPQQPYPQPQPFPSQQPYL. B3144 has proline instead of glutamine in position 34. The previously described peptide B3142 [this journal (1984) 179:371-376] corresponds to B3144 except for the missing C-terminal leucine. PMID- 1519389 TI - Proteolytic activity of isolated lamb calpains on myofibrils under the conditions of pH, Ca2+ concentration and temperature existing in postmortem muscle. AB - The two calcium-activated neutral proteinases (calpains I and II) and their specific inhibitor were isolated by ion exchange chromatography in DEAE-Sephacel from lamb skeletal muscle (longissimus dorsi). Their proteolytic activities were then determined using myofibrils as substrate. The Ca2+ requirements were different for each form of the enzyme: calpain I needed only 50 mumol Ca2+ for half-maximal activity, while the other isoenzyme, calpain II, needed 1,000 mumol Ca2+ for reaching 50% of its maximum activity. Both calpains showed a relevant activity in the pH range 5.5-6.5 (over 40% of maximum activity found at pH 7.5). With regard to the effect of temperature, both isoenzymes retained about 25% of their activity at 25 degrees C with a temperature reduction down to 4 degrees C. It is concluded that calpain I is an active protease under conditions similar to that prevalent in lamb meat during postmortem storage. PMID- 1519390 TI - [Surgical treatment of esophageal cancer: Part I. European results 1980-1991]. AB - During the past 10 years, postoperative mortality associated with resection of oesophageal carcinoma has been reduced from 30% to 11%. However, all efforts to improve longterm survival with extensive excisional procedures and adjuvant chemotherapy and radiotherapy have failed. Fifty-three of 100 patients presenting to the surgeon with an oesophageal carcinoma have resectable disease. Six of them will die from postoperative complications and 47 patients will be discharged from the hospital after an average of 3 weeks. Of these patients, 30 will survive the first, 17 th second, and 7 the fifth year. Although in may be possible to further reduce postoperative complications and mortality, the chances of improving the long-term prognosis of patients with oesophageal carcinoma seem small. PMID- 1519391 TI - [Comparative analysis of mezlocillin/metronidazole and amoxicillin/clavulanic acid as "one shot" preventive antibiotic administration in colorectal interventions]. AB - The prophylactic effect of intraoperative "one shot" antibiotic application in colorectal surgery was investigated. Patients were randomised and the antibiotic combination Mezlocillin/Metronidazole (group A) or Amoxicillin/Clavulamid acid (group B) was applicated in 160 patients. 111 patients were selected for the study (group A: 59; group B: 52 patients). In the postoperative course 53% (group A) and 67% (group B) of the patients developed bacterial infections. Abdominal wound healing was complicated by infection in 15% (A) and 12% (B) of the patients. A significant difference between the two groups could not be proven, 24% of all patients with documented intraoperative bacterial contamination and 10% of the patients with negative findings developed wound infections. In colorectal surgery patients are still at high risk for infectious complications. Applicated antibiotics should basically cover aerobic and anaerobic germs. PMID- 1519392 TI - [Measurement of serum protein-bound hexose--an aid in the diagnosis and after care of colorectal cancers?]. AB - In a group of 80 patients with colorectal carcinoma and a control group of 103 persons Protein-bound Hexose (PHex) was measured in the serum. The level was, as reported previously by other authors, significantly elevated in the tumour group. The aim of this study was to compare the sensitivity of PHex with that of the oncofetal antigens CEA and CA 19/9. The sensitivity of PHex turned out to be clearly lower than that of CEA. It was about as high as the sensitivity of CA 19/9 in colorectal carcinoma. In view of these results there is no benefit to be expected from an introduction of the PHex determination into clinical practice. PMID- 1519393 TI - [Injuries of the portal vein and vena cava in severe blunt abdominal trauma]. AB - Between 1/87 and 7/90 54 severely traumatized patients underwent emergency laparotomy because of blunt abdominal trauma. In 55.5% of the cases one intraabdominal organ, in 20.4% two organs, in 16.6% three and in 7.4% four or more organs were injured. Additionally in 14.8% of these cases (n = 8) a major vascular injury (portal vein n = 5, vena cava n = 2, mesenteric root n = 1) was found intraoperatively. Injuries of the portal vein were always associated with complete rupture of the pancreas, requiring left pancreatic resection in 4 cases and a duodenum preserving resection of the pancreas head in one case. In 2 of these patients the portal vein had to be reconstructed with a prosthesis. Lethality was 9.3% for the whole group (n = 54) and 25% for the patients (n = 8) with additional vascular injuries. PMID- 1519394 TI - [The importance of puncture cytology in diagnosis of benign and malignant breast changes]. AB - In 500 mamma needle biopsies that were cytologically examined we found a precision of 87.4%, with 2.6% false negative, and 6.2% false positive results. In 19 cases a cytological diagnosis was not possible resulting in a sensitivity of 0.94 and a specificity of 0.86. False positive findings were due to misinterpretations of the cytological pictures, as were also false negative findings. In the latter cases sampling mistakes could also be the reason. Cytological diagnostic should only be made using triple diagnostic technique since the methods are complementary to each other in respect to their diagnostic security. Practical experience in the puncturing technique as well as an experienced cytologist are prerequisites using this method successfully as a diagnostic tool. PMID- 1519395 TI - [Lobar restricted nodular form of pulmonary alveolar proteinosis]. AB - A case report of a 53-year-old man with lobar restricted pulmonary alveolar proteinosis is presented. The way from an accidental X-ray examination until the final histological diagnosis of the specimen taken at operation is followed. Typical diagnostic pitfalls are discussed. PMID- 1519396 TI - [Ender nailing versus dynamic hip screw--a comparison of early postoperative results]. AB - Proximal fractures of femur may be alternatively treated by implantation of dynamic hip screws or Ender-nails. Estimation of the value of both measures is to be done by analysis of the early postoperative course. Full load bearing capability was obtained in 83% of all cases with Ender-nails as against 68% of all cases after implantation of hip screws. Duration of operation was clearly shorter and the need for blood transfusions was reduced by implantation of Ender nails. The amount of specific technical complications was equal in both procedures. There were no differences in the postoperative ability to walk. PMID- 1519397 TI - [Interdisciplinary treatment strategy of aneurysmal bone cyst]. AB - In this report the management of an aneurysmal bone cyst in the cervicothoracic region of an 13-year-old girl is described. Aneurysmal bone cyst is a histologically benign lesion that is often extremely vascular. In the spine, it can cause extensive bone destruction and compress neural structures and this can result in high-grade tetraparesis. In the treatment a three-stage operation with radical total removal of the cyst from two posterior approaches and one anterior approach for osteosynthetic stabilisation gave an excellent result. The value of preoperative embolization to reduce tumor vascularity, allowing total excision without neurological deficits to the patient, is demonstrated. PMID- 1519398 TI - [Intralobar pulmonary sequestration--diagnosis and therapy]. PMID- 1519399 TI - [Puerperal inversion of the uterus--a rare obstetric complication]. PMID- 1519400 TI - [Holistic-psychosomatic aspects of surgical organ loss]. AB - Surgical interventions in gynaecology are from a holistic, psychosomatic perspective equally essential interventions into the life history of the treated women. Using a review of international research literature dealing with coping processes after hysterectomy and breast surgery, the author discusses possible psychological and psychopathological consequences of these operations. In addition the presents possibilities for improving as well the preoperative doctor patient-dialogue as postoperative psychotherapeutic and body therapeutic strategies. PMID- 1519401 TI - [Production of prostacyclin in human umbilical cord blood vessels. Effect of natural and synthetic estrogen]. AB - This investigation was conducted to evaluate the effects of 17 beta-estradiol and 17 alpha-ethinylestradiol on prostacyclin PGI2-production in homogenates of human umbilical cord arteries and veins in the presence of exogenous arachidonic acid. The incubation of 17 beta-estradiol at 2 different concentrations (10(-8) and 10( 6) M) in the presence of arachidonic acid for various times (5 min up to 24 h) effected an increase in the production of PGI2 (measured as 6-keto-prostaglandin F1 alpha) of 36-47% in the artery and 16-21% in the vein over basal values (100%). Under the same experimental conditions with 17 alpha-ethinylestradiol we observed an increases of 30-40% in the artery and 1-18% in the vein compared with basal values. For both estrogens this was not significantly different compared with untreated samples. In our in vitro system, natural and synthetic estrogens had no clear effect on PGI2 production in homogenates of human umbilical vessels. PMID- 1519402 TI - [Suitability of metric structural criteria in vaginal ultrasound assessment of the postmenopausal endometrium]. AB - In 135 postmenopausal women ultrasonic findings of the endometrium were compared with the final histopathology. Object of this study was to evaluate the ability of metric structural criterions for a vaginosonographic screening of benign and malignant endometrial neoplasms. A sonographic assessment of the endometrium was possible in 97.8% of the patients; anatomic peculiarities such as calcified fibromyomata proved to be the main-impediments. By means of the criterions examined the sensitivity for the differentiation of inconspicuous and pathological findings was 100% with a 98.2% specificity; the rate of wrong positive results was 1.6%. In 9.2% ultrasound was classified as conspicuous requiring further controls. According to these results the vaginosonographic assessment of the endometrium regarding its thickness and structure (homogeneity, echogeneity, median echo) can be recommended for a non-invasive screening for endometrial neoplasms. PMID- 1519403 TI - [Cryosurgery of condylomata acuminata gigantea--a contribution to therapy]. AB - Two cases of condylomata acuminata gigantea treated with cryosurgery are described. A clinical and histologic differentiation from Buschke-Loewenstein's tumours, sex-specific differences, possible malignant transformations and differential diagnostic diseases are described and references are made to confusions with condyloma-like, primary carcinomas. Compared to conservative surgical treatment of condylomata acuminata gigantea, cryosurgery offers the advantage of rapid necrosis of the condylomata which are repelled without any further surgical intervention and heal without scars. Therefore we consider cryosurgery a more refined technique in treatment of condylomata acuminata gigantea. In extensive involvement, however, cryosurgical measures must be repeated. PMID- 1519404 TI - Comparison of Mycoplasma bovis strains based on SDS-PAGE and immunoblot protein patterns. AB - Whole-cell protein patterns generated by sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) were compared for 34 isolates of Mycoplasma bovis. A high degree of similarity between most of the strains was established with strain-to-strain differences mainly confined to quantitative variations of certain protein bands, particularly in the molecular weight regions of 64-68, 55 and 26 kD. Two of the isolates provided more deviating patterns. Hydrophobic membrane protein fractions of the strains as prepared by Triton X-114 phase partitioning were compared by SDS-PAGE, which confirmed some of the characteristic strain features found with whole-cell proteins. The immunoblot analysis revealed that up to 20 of the 50-55 discrete protein bands detected in SDS-PAGE patterns were recognized to be antigenic by rabbit and bovine hyperimmune sera. It is concluded that the same set of major antigens is present in all strains investigated, but amounts of individual constituents may be differing. PMID- 1519405 TI - Relevance of sensitivity testings (MIC) of S. aureus to predict the antibacterial action in milk. AB - Bacterial susceptibility testings were carried out in parallel Iso-sensitest broth (ISB) and bovine milk cultures using 16 antibacterials and 4 sensitive strains of mastitic isolates of Staphylococcus aureus. Bacterial activities were analyzed by continuous turbidity monitoring (broth cultures), continuous fluorometric monitoring of the resazurin-reducing redox activity, and by analyzing the triphenyltetrazolium (TTC)-reducing capacity at the end of the incubation period. To obtain an equipotent bacteria-suppressing activity, milk cultures required in general several times more antibiotic than the respective ISB cultures. Antibacterial activities of sulfadoxine-trimethoprim, vancomycin, novobiocin, macrolides, aminoglycosides and oxytetracycline were most effectively suppressed by milk. Aminoglycosides suffered additionally from reduction of oxygen in the incubation environment. The beta-lactams (penicillin G, oxacillin, cephalothin, ceftiofur, ampicillin, ampicillin-clavulanic acid), gentamicin and enrofloxacin showed extremely variable sensitivity results depending on the S. aureus/milk combination. PMID- 1519406 TI - The early migration of Elaphostrongylus rangiferi in goats. AB - The migration of nematodes of the genus Elaphostrongylus (Metastrongyloidea: Protostrongylidae) from the gut into the tissues of ruminants has not been described. Detailed histologic studies were performed on five goat kids that had received oral doses of 1,000-1,500 infective larvae of Elaphostrongylus rangiferi Mitskevich, 1960 and were subsequently autopsied at days 2, 4, 6, 10, and 14 post inoculation. The main migratory route of E. rangiferi larvae seemed to be haematogenous. The larvae penetrated the venules of the abomasum and followed the blood stream via the liver to the lungs. In the lungs, the larvae entered pulmonary venules and passed into the arterial circulation reaching the central nervous system (CNS) and other organs between days 6 and 10 post inoculation. Some of the larvae that had lodged in tissues outside the CNS probably migrated into it along the spinal nerves. A marked eosinophilia was present from day 8 post inoculation. PMID- 1519407 TI - Evaluation of the API Coryne test system for identification of Actinomyces pyogenes. AB - The present study was designed to evaluate the accuracy of the API Coryne test system for identification of Actinomyces pyogenes. The test system correctly identified 36 of 42 A. pyogenes and 4 of 5 comparatively studied Arcanobacterium haemolyticum-cultures. The biochemical profiles of the remaining 6 A. pyogenes- and 1 A. haemolyticum-cultures were not included in the analytical profile index. None of the cultures were misidentified. According to the API database (ATB Plus V 1.5.4.) the unidentified cultures could be correctly identified as A. pyogenes and A. haemolyticum respectively. A greater repertoire of A. pyogenes specific biochemical profiles incorporated into the analytical profile index would improve the applicability of this test system for veterinary diagnostics. PMID- 1519408 TI - Evaluation of the effect of 3 probiotics on experimental Escherichia coli enterotoxaemia in weaned piglets. AB - In this report the efficacy of 3 different probiotics (Bacillus cereus "toyoi", Lactobacillus spp. and Streptococcus faecium) was investigated. They were supplemented in the food of recently weaned piglets that were orally infected with E. coli O141 K85ab. Supplementation could not prevent mortality and clinical symptoms nor reduce the faecal excretion of hemolytic E. coli. The possible explanations for the unsatisfying results are various. PMID- 1519409 TI - Opsonic activity in mammary secretion and serum of gilts during the lactation period. AB - Opsonic activity was studied in mammary secretion and serum during lactation in four healthy gilts. The opsonic activity was determined as peak chemiluminescence and time to peak chemiluminescence in a luminol enhanced chemiluminescence assay. The peak chemiluminescence was significantly (p less than 0.05) higher in mammary secretion around parturition than later in lactation. No changes in the opsonic activity were seen in serum during lactation. Overall, the peak chemiluminescence and time to peak chemiluminescence were significantly higher (p less than 0.001) and shorter (p less than 0.05) respectively, in serum than in mammary secretion. The present study indicates that the opsonic activity is highest in mammary secretion around parturition but decreases later in lactation, and that this change is confined to the mammary gland. PMID- 1519410 TI - Cytotoxicity of cyanobacterium Microcystis aeruginosa. AB - Cytotoxic effects of crude extracts and fractions of the purification steps towards Microcystin-LR (MCYST-LR) were investigated in vitro. Cytotoxicity was evaluated by measure of lactate dehydrogenase liberation of Chang liver cells and by hemolysis. Crude extracts of strain PCC 7806 damaged the cells within a few minutes. In contrast, MCYST-LR did not show any detectable cytotoxic effects. The cytotoxic activity could be related to a heat-labile substance with a molecular weight of about 30,000 Da. PMID- 1519411 TI - Haematology of experimental babesiosis and ehrlichiosis in steroid immunosuppressed horses. AB - An investigation was carried out to study the haematology of steroid immunosuppressed horses experimentally infected with Babesia equi and Ehrlichia equi, separately or simultaneously. Horses infected with both pathogens showed less marked changes in their haematology than those inoculated with either pathogen separately. This appeared to result from early elimination of the more pathogenic Babesia as Ehrlichia spread through the granulocytes. The apparent suppression of Babesia by Ehrlichia is of field clinical importance and merits further investigation for its apparent useful potentials in the control of babesiosis in endemic areas. PMID- 1519412 TI - Preparation and characterization of monoclonal antibodies against Mycoplasma bovis. AB - Monoclonal antibodies (mabs) against Mycoplasma (M.) bovis were prepared for use in diagnosis of bovine mastitis. From the original 32 hybridomas actively secreting mabs against M. bovis, 6 stable lines were cloned. Two of them, Mb 5D8 and Mb 4F6, recognized M. bovis antigens of estimated molecular weights of 33 and 26 kDa, respectively. They showed no cross-reaction to other bovine mycoplasmas, thus rendering them useful for specific detection of this pathogen. All mabs investigated cross-reacted with M. agalactiae which is known to be closely related to M. bovis, but does not occur in cattle. Two other mabs, Mb 5D4 and Mb 1F6, exhibited further cross-reactions to a number of bovine mycoplasma species. Finally, mabs Mb 5D5 and Mb 2G5 reacted with all mycoplasmas tested. The possibility that they recognized constituents of the broth culture medium is discussed. PMID- 1519413 TI - The isolation and identification of Leptospira interrogans serovar bratislava from a pig in Germany. AB - During a study on the improvement of selective media for the isolation of leptospires from clinical material, leptospires were isolated from the kidneys of a pig. Test material was cultured in EMJH-medium containing 0.4% rabbit serum and 3 inhibitory substances (Rifampicin 10 micrograms/ml, Amphotericin B 2 micrograms/ml, 5-Fluorouracil 100 micrograms/ml). The cultured leptospira-strain (Berlin 406) was identified to serogroup level using the cross agglutination method and it was further typed to serovar level by MAB's, factor analysis and restriction endonuclease analysis (REA). MAB typing of Berlin 406 gave an agglutination pattern profile typical of serovar bratislava. Factor serum identification clearly identified this strain as serovar bratislava. On REA examination, Berlin 406 gave a profile identical to that of the serovar bratislava type strain Jez Bratislava i.e. genotype B1. This is the first report of a confirmed isolate of Leptospira interrogans serovar bratislava from domestic animals in Germany. There exist a number of possibly important implications as this agent is being incriminated in the cause of clinical disease not only in pigs, but also in horses and dogs in other countries. PMID- 1519414 TI - The overwintering of Fasciola hepatica eggs under semi-arid and temperate Mediterranean climate (Madrid, Spain). AB - In this experimental work, conducted over two consecutive years (1988 and 1989), we have analyzed the overwintering possibilities of Fasciola hepatica eggs deposited in winter in a semi-arid and temperate Mediterranean area (Madrid, Spain). Eggs did not survive for more than a week in faeces at environmental moisture conditions. In contrast, over a 75% of the eggs maintained in permanently wet faeces survived winter temperatures, showing no high mortality until important thermic increment from June. The success of overwintering was higher in eggs arrested in wet faeces than included in water (55% "versus" 20% of hatching in spring), and it was unrelated to the deposition time (excretion in early or late winter). The hatching period of overwintered eggs started in May, at the same time as those excreted in early spring. Therefore, overwintering of eggs will have an effect on the level but not on the start of the spring contamination with miracidia. The dry winters of this semi-arid area greatly restrict the overwintering eggs contamination to soils next to streams, ponds or irrigation channels. PMID- 1519415 TI - Relationship between group B streptococcal serotypes and cell surface hydrophobicity. AB - Cell surface hydrophobicities of streptococci of serological group B were determined by the adherence of the bacteria to hexadecane droplets. A significant adherence to hexadecane was observed with the group B streptococcal type reference strains Ib, V, Ic, R and X, but not with those of serotype Ia, II, III and IV. Cultivation of the bacteria in microcapsule-inducing media reduced the hexadecane adherence properties. The adherence to hexadecane was not related to fibrinogen binding properties of the cultures. Screening a large number of group B streptococci isolated from humans and bovines revealed that those with polysaccharide type antigen alone were generally hydrophilic, those with protein antigen alone or with protein antigen in combination with polysaccharide antigen were mostly hydrophobic. Cultivation of the bacteria under microaerobic conditions or after a single mouse passage enhanced microcapsule production and correspondingly reduced the hexadecane adherence values. Treatment of the bacteria by guanidinium chloride or by neuraminidase enhanced the hexadecane adherence. The hydrophobic component on group B streptococcal surface appeared to be partly inactivated by heat or proteolytic treatment of the bacteria. PMID- 1519416 TI - Characterisation of Newcastle disease viruses isolated in India. AB - Eleven Newcastle disease virus (NDV) isolates obtained from outbreaks of disease in chickens (9) and Japanese quail (2) in Tamil Nadu, India were characterised in pathogenicity tests, antigenically, using mouse monoclonal antibodies (MAbs), and other established tests devised to distinguish between different strains. All 11 isolates were shown to be highly virulent for chickens. In indirect immunoperoxidase tests used to assess the ability of a panel of 28 MAbs to bind to infected cell cultures, 10 of the isolates showed an identical reaction pattern, the other isolate (No. 4) failed to react with one MAb which bound to cells infected with the other isolates. Isolates 9 was unstable at pH 3 while the other 10 were stable. All other properties were shared by the 11 isolates. PMID- 1519417 TI - Mechanism of impaired growth hormone secretion in patients with Cushing's disease. AB - The function of the growth hormone-releasing hormone (GHRH)-growth hormone (GH) axis in Cushing's disease was studied by monitoring (a) the GH responses to GHRH loading and L-dopa loading, (b) the GHRH response to L-dopa loading, and (c) the daytime profiles of plasma GH concentration. GH release following GHRH and L-dopa was blunted in patients as compared to that in age-matched control subjects. However, GHRH release following L-dopa was similar in patients and controls. The plasma GH levels in four patients measured every 20 min by a highly sensitive immunoradiometric assay for GH showed pulsatile GH secretion at low levels during the observation period. These results indicate that GHRH release from the hypothalamus is preserved in patients with Cushing's disease, and support the hypothesis that glucocorticoid inhibits GH secretion by altering the hypothalamic somatostatin tone. PMID- 1519418 TI - Alterations in circadian rhythm of serum thyrotropin in critically ill patients. AB - To evaluate the 24-h pattern of serum thyrotropin (TSH) in critically ill patients, we measured serum concentrations of TSH in blood samples collected every 2 h for 24 h from nine patients (six with malignancy, two with liver cirrhosis, one with chronic renal failure), who had subnormal levels of both triiodothyronine (T3) and thyroxine (T4), in the absence of history, symptoms or signs of thyroid disease. Analysis of the data, performed using a second-order inferential statistical methodology for rhythmometry (cosinor method), demonstrated that critically ill patients still had daily oscillations of serum TSH which significantly adapted to the function approximating the circadian rhythms (R2 = 74.3%). However, the mean level (mesor) in the rhythm of the patients was found to be significantly lower than that of healthy subjects (0.96 vs 2.18 mU/l); the amplitude of rhythmical daily variations also was lower in patients than in healthy subjects (0.23 vs 0.56 mU/l), even though the amplitude/mesor ratio was similar (23% vs 26%). Lastly, the highest level in the TSH rhythm of the patients was found to be in the late afternoon, in contrast to healthy subjects, who had a TSH surge after midnight. Although these alterations are consistent with the existence of a dysregulation at suprahypophyseal level in critically ill patients, it remains to be established whether the state of low T3 and T4 may be ascribed to anomalous circadian rhythm of TSH. PMID- 1519419 TI - Evaluation of the degradation of desamino1,D-arginine8-vasopressin by nasal mucosa. AB - The nasal route is a convenient and simple way to administer peptides to humans. Absorption of the drug, however, requires passage of the substance through the nasal mucosa. This is a possible site of enzymatic degradation of the peptide. It is shown that rabbit nasal mucosa homogenates rapidly degrade the synthetic anti diuretic hormone analogue desamino1,D-arginine8-vasopressin in vitro. The metabolite formed has been identified as des-(amino,arginine8,glycineamide9)- vasopressin, which is stable under the prevalent in vitro incubation conditions. It is proposed that this process is catalyzed by intracellular post-proline cleavage enzyme. Reversed phase chromatography in combination with immunological detection has been used to study the possible presence of this metabolite in the circulation after intranasal administration to humans. The metabolite des (amino,arginine8,glycineamide9)-vasopressin could not be detected in plasma following intranasal administration, possibly indicating a paracellular absorption of desamino1,D-arginine8-vasopressin or absence of this enzymatic activity in humans. PMID- 1519420 TI - Long-term stability of low insulin responses to glucose in non-diabetic subjects. AB - We investigated the stability of the insulin response to glucose in healthy subjects by making retrospective comparisons of insulin responses after two 60 min glucose infusion tests performed many years apart. The subjects (N = 49) were divided into two lower and two higher quartiles as assessed by the incremental 0 10 min insulin area during the initial glucose infusion test. Ages were initially 32.3 +/- 2.8 years in lower quartiles and 26.6 +/- 1.1 in higher quartiles and body mass indexes 21.6 +/- 0.6 kg/m2 and 21.8 +/- 0.5, respectively. The interval between the first and second glucose infusion tests was 8.1 +/- 2.8 years for lower quartiles and 10.4 +/- 1.3 for higher quartiles. In lower quartiles, the 0 10 min insulin area at first testing was 157.1 +/- 15.9 mU/l x 10 min and at follow-up 202.2 +/- 26.6 (+29%, NS). In higher quartiles, the insulin area decreased from 654.8 +/- 70.6 mU/l x 10 min at first testing to 489.8 +/- 53.6 at follow-up (-25%, p less than 0.05). The 0-60 min glucose area did not change significantly between glucose infusion tests in lower quartiles (+5%), but did increase by 12% (p less than 0.005) in higher quartiles. Only one subject of the lowest quartile at first testing changed to higher quartiles at follow-up. Predictable "regression toward the mean" at follow-up was moderate, hence the individual insulin response to glucose was relatively stable with time. This finding is compatible with the hypothesis that genetic factors are of major importance for the insulin response to glucose. PMID- 1519421 TI - Relationship between plasma growth hormone concentration and cellular sodium transport in acromegaly. AB - We investigated the relationship between mean plasma growth hormone (GH) concentration and cellular sodium transport in untreated and treated acromegaly. Seventeen patients (age 55 +/- 3 years) with active acromegaly were studied with respect to plasma GH (mean of 24 h GH profile) and erythrocyte electrolyte content as well as transmembrane sodium transport. The patients were reinvestigated two weeks after successful surgery (N = 14) and again after one year (N = 13). Erythrocyte electrolytes were analyzed by flame photometry and sodium influx and efflux rate constant determined by in vitro incubation using a modified Keyne's formula. In patients with active acromegaly there was a significant positive correlation between IGF-1 and cellular sodium transport, while GH tended to show a negative relationship to the same parameter. After successful treatment, both IGF-1 and GH disclosed a positive relationship to cellular sodium transport. After one year, a significant increase in erythrocyte sodium content was seen in the patients compared to the preoperative situation. In conclusion, if this is a generalized phenomenon the results are compatible with a sodium-retaining effect of GH via stimulation of transmembrane sodium transport. In active acromegaly this may be counteracted by a sodium transport inhibitor giving the reverse relationship between GH and cellular sodium transport. PMID- 1519422 TI - Immunoglobulin G of patients with circumscribed pretibial myxedema of Graves' disease stimulates proteoglycan synthesis in human skin fibroblasts in culture. AB - Hyaluronic acid and proteoglycan accumulate in the affected skin of Graves' disease patients with pretibial myxedema (PTM). We aimed to determine whether an autoantibody IgG circulating in PTM patients stimulates proteoglycan synthesis in human skin fibroblasts, resulting in PTM. IgGs were purified from 14 normal subjects, 11 Graves' disease patients with PTM. 5 Graves' disease patients with active ophthalmopathy and 15 Graves' disease patients with neither PTM nor ophthalmopathy. Human skin fibroblasts were incubated with the IgGs and labeled with [35S]sulfate. The medium and cell layer were separated and the proteoglycan was extracted. The 35S radioactivity in the proteoglycan fraction was measured. Compared with normal IgGs or with those of Graves' disease without PTM or ophthalmopathy, PTM IgGs significantly increased the incorporation of the 35S into the proteoglycan. The effect of PTM IgG was dose-dependent. As PTM IgG did not alter degradation of the 35S labeled proteoglycan, an increase in 35S incorporation reflects increased synthesis. The effect was mediated through a mechanism other than adenylate cyclase activation. The present study demonstrates the presence of an autoantibody in PTM IgG that stimulates proteoglycan production through human skin fibroblasts. This is not correlated with the thyroid stimulating antibody activity. It is suggested that the activity of this antibody leads to the development of PTM. PMID- 1519423 TI - Serum and plasma epidermal growth factor in thyroid disorders. AB - Epidermal growth factor (EGF) is an important mitogen and its secretion in neonatal animals has been shown to be affected by thyroid hormone levels. EGF in blood of humans is found in both platelets (as reflected in its serum level) and in plasma; its origin in plasma remains unclear. Serum and plasma EGF were studied in a group of patients with thyroid disorders. Twenty hyperthyroid subjects (3M, 17F) aged 37.3 +/- 14.9 years and 10 hypothyroid patients (3M, 7F) aged 58.3 +/- 18.6 years were studied before and after euthyroidism was restored. Before treatment, serum EGF in the hyperthyroid patients was elevated compared to normal controls (501 +/- 376 vs 270 +/- 154 pmol/l, p less than 0.001). After treatment of hyperthyroidism, serum EGF returned to the normal levels (232 +/- 176 pmol/l). In contrast, serum EGF was not significantly different in the hypothyroid subjects either before or after treatment (151 +/- 194 and 237 +/- 153 pmol/l respectively). A significant correlation (r = 0.461, p less than 0.001) between serum EGF and serum-free thyroxine index (FTI) was found when all samples from both untreated and treated hyper- and hypothyroid patients were examined. Multiple regression analysis revealed that both serum FTI and platelet count independently affected the serum EGF levels. Similarly, plasma EGF was also elevated in untreated hyperthyroid patients with a median of 26.4 pmol/l (range less than 16.6-88.0), whereas all normal controls and hypothyroid subjects had unmeasurable levels.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1519424 TI - Cerebrospinal fluid and blood concentrations of luteinizing hormone, follicle stimulating hormone and prolactin following castration of adult male rats. AB - Comparative levels of LH, FSH, and PRL in the serum and cerebrospinal fluid (CSF) of adult male rats were studied at different periods following castration. Intact and sham-operated animals served as controls. Blood and CSF were collected at 1, 3, 7, 14, 21, 28, 35 and 46 days following castration. The CSF was collected via cisterna-magna puncture, while the blood was collected from abdominal aorta. Serum gonadotropins increased progressively beginning day 1 post-castration to reach maximum by day 35 or 46 post-castration. Sham operation and castration did not affect mean CSF, LH and FSH levels compared to intact controls. Analysis of the temporal pattern of serum and CSF gonadotropin levels following castration revealed significant positive correlation between CSF and serum LH (r = 0.58) and FSH (r = 0.64) levels respectively. The data suggest that CSF gonadotropins may be derived from systemic circulation. Serum PRL levels were not affected by castration, but CSF PRL levels were significantly reduced at days 28, 35 and 46 post-castration compared to intact controls. CSF PRL levels showed negative correlation with serum LH and FSH levels but failed to show a correlation with serum PRL levels. Hypothalamic norepinephrine turnover rate increased at days 28, 35 and 46 post-castration. Hypothalamic dopamine contents and turnover rates were reduced at days 21 and 28 post-castration. It is suggested that CSF PRL may have a role in the regulation of serum gonadotropins. PMID- 1519425 TI - Primary culture of prepubertal human testicular cells isolated from testes collected at necropsy. AB - The aim of the present work was to develop a method for maintaining prepubertal human testicular cells in culture. Seven pairs of testes of boys who died of causes unrelated to endocrine or metabolic diseases were obtained at necropsy. Histology of the testes was normal. Testes were digested with collagenase and dispersed cells were seeded in multi-well dishes in the presence of 5% bovine fetal serum. After the first day, cells were cultured for five days in serum-free medium in the presence or absence of 918 pmol/l insulin. At the end of culture, microscopic examination showed healthy looking cells with characteristics compatible with pre-Sertoli cells; peritubular cells were identified by immunocytochemistry. In the presence of insulin, cells were able to secrete either testosterone or estradiol into the medium, as well as to reveal aromatase activity. In order to study the effect of the time elapsed between death and beginning of cultures, steroidogenic activity was related to this post mortem time. It was found that, in the presence of insulin, cells obtained from testes with less than 24 h of post mortem time secreted testosterone (64 +/- 7.2 pmol/10(6) cells.24 h, mean +/- SD) while cells obtained from testes with more than 24 h of post mortem time did not secrete testosterone. With long post mortem times, aromatase activity under insulin increased from non-detectable to 35 pmol/10(6) cells.24 h. Time course studies showed that cells with capacity to secrete testosterone increase this secretion gradually up to day 10 of culture, while those with detectable aromatase activity showed increments in this activity during the first week of culture.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1519426 TI - Growth hormone secretion in patients with Turner's syndrome as determined by time series analysis. AB - Twenty-four-hour growth hormone (GH) profiles in 26 girls with Turner's syndrome were compared with those of 26 normally growing short children and 24 slowly growing short children. All children were prepubertal and below 12 years of age. A subgroup of 13 girls was treated with ethinyl estradiol and a 24-h GH profile was reassessed. In an additional group of 45 girls with Turner's syndrome (aged 6.7-18.9 years) the effect of age, spontaneous breast development and ethinyl estradiol treatment was studied. The profiles were assessed by Fourier analysis. The oscillatory activity and the mean 24-h GH concentration were similar in children with Turner's syndrome and the normally growing short children, in contrast to lower levels in the slowly growing short children. The periodicity of GH secretion was similar in all groups. In the longitudinal study, ethinyl estradiol treatment resulted in a significant increase in pulse amplitude, but not in periodicity. In the cross-sectional study there was no significant difference between the subgroups of girls with either presence or absence of breast development or ethinyl estradiol treatment. GH secretion was not significantly related to age, height in standard deviation score or height velocity. These data imply that there is no abnormality in GH secretion in girls with Turner's syndrome. PMID- 1519427 TI - Effects of thyroid hormones on mitochondrial oxygen consumption in brown adipose tissue and heart from cold-exposed hypothyroid rats. AB - The present work measured brown adipose tissue and heart mitochondrial oxygen consumption in hypothyroid rats treated with replacement doses of T3, T4 or T4 plus iopanoic acid and kept at 4 degrees C for 24 h. Heart oxygen consumption in normal, untreated hypothyroid and T4-treated hypothyroid rats was unaffected by cold exposure. In rats treated with T4 plus iopanoic acid, rates of oxygen consumption were normal in those maintained at 4 degrees C as well as in those kept at room temperature, despite serum T3 concentration being significantly decreased. The cold-exposed T3-treated hypothyroid rats showed a marked decrease in oxygen consumption (p less than 0.02) and alpha-glycerophosphate dehydrogenase activity, a T3-dependent enzyme. Mitochondrial oxygen consumption in brown fat from normal (p less than 0.01), T4 (p less than 0.02) and T4 plus iopanoic acid treated (p less than 0.01) rats rose more than twofold in response to cold. In the T3-treated group, oxygen consumption at room temperature was higher (p less than 0.02) than in any other group at similar temperatures. However, the T3 treated group showed no changes in oxygen consumption in response to cold, perhaps because this group reached the maximal response at room temperature. The untreated and the T3-treated hypothyroid rats (both groups devoid of T4) did not survive at 4 degrees C unless T4 or several-fold replacement amounts of T3 were administered. The data demonstrate the crucial role of T4 in thermogenesis during cold exposure. PMID- 1519428 TI - Decrease of testosterone level during an experimental African trypanosomiasis: involvement of a testicular LH receptor desensitization. AB - To investigate gonadal disorders and changes of the testicular receptors occurring during the sleeping sickness disease (African trypanosomiasis), an experimental model was developed with 10-month-old rats infested by bloodstream forms of two variants of Trypanosoma brucei brucei (AnTat 1.1 A and AnTat 1.8). At the acute phase, three days after inoculation, the animals were sacrificed for estimating the serum levels of LH and testosterone and the number of testicular LH receptors. Considering a possible intervention of the stress during the infestation and to improve our investigations on gonadal imbalance related to trypanosomasis, levels of additional parameters [corticosterone, glucose and transaminases (glutamic-oxaloacetic transaminase and glutamic-pyruvic transaminase)] were determined. Stimulation testing with hCG was likewise assessed in infested rats to analyse the testicular testosterone response to gonadotropin. A significant decrease was demonstrated for serum LH and testosterone levels in the infested rats, as well as the loss of: (i) the testicular responsiveness to exogenous gonadotropin; (ii) the number of testicular LH receptors. Moreover, the remaining testicular receptors of infested rats showed an increase in their equilibrium association constant (Ka). Our study suggests that dysfunction of Leydig cells occurring during African trypanosomiasis is in part related to stress induced by the presence of the parasites. PMID- 1519429 TI - Effects of growth hormone releasing hormone on insulin action and insulin secretion in a hypopituitary patient evaluated by the clamp technique. AB - The effect of growth hormone releasing hormone (GHRH-44) therapy on insulin action and secretion was evaluated in a hypopituitary patient after one month and one year of treatment. Hepatic and peripheral insulin action was studied with the hyperinsulinemic-euglycemic clamp in combination with [6,6-2H2]glucose tracer infusion. First and second phase insulin secretion was assessed with the hyperglycemic clamp. Prior to GHRH-44 therapy the hypopituitary patient had higher insulin mediated glucose disposal rate and lower basal and stimulated insulin concentrations by more than two standard deviations from the mean of a control group. Following therapy there was no change in basal hepatic glucose production; however, there was evidence of diminished peripheral insulin action. This was manifested by decreased insulin mediated glucose disposal during the hyperinsulinemic-euglycemic clamp, and increased insulin secretion during the hyperglycemic clamp. We conclude that GHRH-44 therapy in this patient was associated with decreased peripheral insulin action which was compensated for by increased insulin secretion. PMID- 1519430 TI - Deformability of the erythrocyte membrane in patients with myelodysplastic syndromes. AB - One of the major determinants of erythrocyte survival is membrane deformability, and an important intrinsic parameter of membrane deformability is the shear elastic modulus (mu) with higher mu values corresponding to increased membrane rigidity. Using a micropipette technique, we determined the shear elastic modulus of erythrocytes from 21 patients with myelodysplastic syndromes (MDS). Ten thalassemic patients and 15 healthy subjects served as controls. The shear elastic modulus of MDS erythrocytes was very significantly increased in all the patients studied, reflecting the rigidity of the membrane; the value of mu was also significantly higher in comparison with thalassemic cells. These data point to a fundamental change in the mechanical properties of the erythrocyte membrane in MDS. Biochemical studies of the membrane composition are clearly needed. PMID- 1519431 TI - Aggressive chemotherapy for acute leukemia relapsed after bone marrow transplantation: a second chance? AB - Eight patients, 5 with acute non lymphoid leukemia and 3 with lymphoid leukemia, were treated at relapse after bone marrow transplantation (BMT; 4 autologous BMT and 4 allogeneic BMT). Of these, 2 relapsed within 3 months after BMT (2 allogeneic BMT) and 6 (2 allogeneic and 4 autologous BMT) after more than 9 months after BMT. The 2 patients relapsing early showed no response to treatment and died. Five out of 6 patients relapsing late achieved complete remission (4 of them with intensive chemotherapy). Four patients are currently alive. Aggressive combination chemotherapy can produce long-term survival in selected patients relapsed after BMT. PMID- 1519432 TI - Splenic megakaryocytopoiesis in primary (idiopathic) osteomyelofibrosis. An immunohistological and morphometric study with comparison of corresponding bone marrow features. AB - An immunohistochemical and morphometric study has been performed on splenic tissue of 10 patients with primary (idiopathic) osteomyelofibrosis (OMF) to determine characteristic features of megakaryocytopoiesis in myeloid metaplasia. Using the periodic acid-Schiff reaction (PAS) and particularly the monoclonal antibody CD61 (Y2/51), all elements of this cell lineage including precursors could be identified. In comparison with bone marrow specimens from our file material (40 patients with OMF, 15 control cases) which were processed in a similar way, megakaryocytes in the spleen revealed significant differences. These differences included smaller cell sizes, a disturbed nuclear-cytoplasmic ratio, and a conspicuous increase in the relative frequency of promegakaryoblasts. In conclusion, extramedullary megakaryocytopoiesis in OMF did not only show more pronounced abnormalities of differentiation, but also a higher degree of immaturity. Our finding of a significant accumulation of megakaryocytic precursors in the spleen as opposed to the bone marrow, corroborates the so called filtration theory which has been introduced to explain the evolution of splenic myeloid metaplasia in OMF. PMID- 1519433 TI - Felty's syndrome: favorable response to granulocyte-macrophage colony-stimulating factor in the acute phase. AB - We report a case of Felty's syndrome in which infectious complications due to severe neutropenia could be overcome by short-term treatment with recombinant human granulocyte-macrophage colony-stimulating factor (GM-CSF, 7 micrograms/kg/day s.c.). Leukocyte counts rose from 1,050/mm3 at presentation to 4,470/mm3 after 15 days of treatment. A flare-up of arthritis was not noted. Defects in granulocyte function and clinical improvement prior to leukocyte rise suggest that the beneficial effect of GM-CSF is mainly due to an improvement of granulocyte function. PMID- 1519435 TI - 11;13 translocation in acute nonlymphocytic leukemia. AB - In this paper, we report on a 9-year-old girl with acute nonlymphocytic leukemia (FAB-M5) with a rare chromosome abnormality, t(11;23)(q21;p11). Peripheral blood showed Hb 7.5 g/dl, WBC 3,600 cells/microliters (10% blasts), and platelet count 110 x 10(3) cells/microliters. The bone marrow aspirates showed normal cellularity with 36.7% blasts. On morphological characteristics, micromegakaryocytes were observed, and on chromosome examination the karyotype was shown to be 46,XX,t(11;13)(q21;p11) in all metaphases. PMID- 1519434 TI - Anemia and neutropenia in a case of copper deficiency: role of copper in normal hematopoiesis. AB - We present a patient who developed severe anemia and neutropenia after receiving parenteral nutrition for 2.5 years. The serum levels of copper and ceruloplasmin were low, and the bone marrow showed the presence of ringed sideroblasts and vacuolated immature cells. The administration of copper chloride by bolus injection led to a rapid improvement in anemia and neutropenia. The number of progenitor cells (colony-forming unit-granulocyte-macrophage and erythrocyte) present before the copper supplementation was well preserved. It is therefore suggested that copper enzymes play an important role in the maturation of hematopoietic cells. PMID- 1519436 TI - Primary adult T-cell lymphoma of the breast. AB - A case of primary adult T-cell lymphoma (ATL) of the breast is described. A 69 year-old woman presented with a painless, rapidly growing lump in her left breast. Staging procedures demonstrated no sign of generalized disease. Following a Patey's mastectomy, 10 courses of adjuvant chemotherapy (CHOP) were successfully administered. The light microscopic, immunohistochemical and molecular genetic analyses of the surgical specimen revealed a primary ATL. Seropositive mothers who breast-feed their children may facilitate the accumulation of T cells carrying HTLV-I in their breasts and thereby increase their risks of developing breast ATL. PMID- 1519437 TI - Pearson's marrow-pancreas syndrome in 2 Turkish children. AB - Two unrelated infants, 1 female and 1 male, with Pearson's syndrome are presented. Both patients presented with severe macrocytic refractory anemia starting early in infancy. Investigation of the mitochondrial (mt), DNA showed that one of the patients had a 4,977 bp deletion, and the other had a 4.5 kb mtDNA deletion. It is concluded that Pearson's syndrome should be borne in mind in the differential diagnosis of refractory anemia especially when there are accompanying gastrointestinal disturbances and metabolic acidosis. PMID- 1519438 TI - Myelokathexis and monocytosis in a patient with gastric cancer. AB - A 66-year-old patient developed leukocytosis, neutrophilia and monocytosis following surgery for gastric carcinoma. The polymorphonuclear cells showed a marked shift to the right and abnormally hypersegmented or pyknotic nuclei, whereas the monocytes were vacuolized. The bone marrow was hypercellular with an increased number of multilobed polymorphonuclear cells. This myeloid cell defect is compatible with the nuclear abnormalities described as myelokathexis. The combination of the nuclear abnormalities of the polymorphonuclear cells with persistent monocytosis suggests the possibility of a paraneoplastic variant of myelodysplasia. PMID- 1519439 TI - Aplastic anemia associated with amiodarone therapy. PMID- 1519440 TI - Rapid method for isolation of DNA from glass slide smears for PCR. PMID- 1519441 TI - Thyroid hormones influence perceptual processing in a visual search paradigm. AB - The mechanisms that mediate the effects of thyroid hormones on higher cognitive processes are not well understood. In the present experiments, event-related potentials (ERPs) and behavioral measurements were recorded in a visual search paradigm where a target item had to be detected in a number of distractor items. 10 healthy subjects were given a daily dose 300 micrograms thyroxine (T4) p.o. and recordings were made before and after 3 weeks of treatment. All subjects developed hyperthyroidism with a completely suppressed TSH (1.6 +/- 0.5 mU/l vs. non detectable), a significant increase in T3 (1.5 +/- 0.2 vs. 1.9 +/- 0.2 ng/ml). T4 (6.6 +/- 1.6 micrograms/dl vs 11.9 +/- 2.7 micrograms/dl) and sex hormone binding globulin (2.9 +/- 1.1 vs. 3.8 +/- 1.3 micrograms/ml; all p less than 0.0005). Compared to the control group (n = 15), thyroid hormones improved controlled serial visual processing, as indexed by changes of the late positive ERP component and target detection hit rate (in both cases p less than 0.01), whereas parallel detection of salient features remained unchanged. The data suggest a differential impact of thyroid hormones on visual information processing. PMID- 1519442 TI - Effects of thyroxine, triiodothyronine and reverse triiodothyronine on the neonatal hypothyroid rat cerebellum. AB - In order to develop a model of thyroid hormone action, we studied the effect of small doses of T3 and T4 on the development of the hypothyroid neonatal cerebellum of rat pubs. Using granulosa cell death at postnatal d15 (picnotic index) as a criterion of hypothyroidism, it was found that a single injection of 50 ng T3/10g bw or 180 ng T4/10 g bw would reduce the picnotic index to levels found in euthyroid rat cerebelli. We further tested if rT3, known to be an excellent blocker of deiodinase type 2 activity, would be able to block the effects of T4. 20 micrograms rT3/10g bw had to be given to be an effective inhibitor in vivo. This dose did not affect the potency of T4 and control experiments with rT3 alone indicated that rT3 was capable of reducing the picnotic index to euthyroid levels. It is speculated that rT3 might act at the nuclear receptor but also at the cell membrane. PMID- 1519443 TI - Homeostasis of brain T3 in rat fetuses and their mothers: effects of thyroid status and iodine deficiency. AB - Faced with large variations in iodine, T4 or T3 supply, the fetal brain is able to maintain T3 homeostasis to a greater degree than apparent from changes in plasma and other tissues, such as the liver. Changes in the activity of 5'D-II play an important role in this homeostasis, although this does not exclude other regulatory mechanism(s), such as changes in type III (5D) activity, in uptake of the iodothyronines by the brain, or in cerebral iodothyronine turnover rates. T3 generated locally from T4 is more important than plasma derived T3 as determinant of the total T3 available to the brain throughout the life cycle of the rat. It is especially important during the fetal and neonatal phases of brain development, when the brain depends almost exclusively on the supply of T4. Fetal brain T3 homeostasis is maintained despite large fluctuations in the supply of T4. An excess of T3 also affects brain T3 to a lesser degree than it does other tissues. If present results are relevant to man, they suggest that overtreatment of mother of a congenital hypothyroid fetus with T4 is not likely to be harmful for the fetal brain. Treatment with T3 should be avoided, as it deprives the fetal brain of the main regulatory mechanism involved in homeostasis of brain T3, namely generation of T3 from T4. PMID- 1519444 TI - The trace components--selenium and flavonoids--affect iodothyronine deiodinases, thyroid hormone transport and TSH regulation. AB - The trace elements iodine and selenium exert major control function on thyroid hormone homeostasis. Appropriate production, transport to target cells, activation of prohormones to yield receptor ligands, and metabolism resulting in the termination of the hormonal signals are influenced by these two trace elements but also by dietary compounds such as flavonoids. Flavonoids, ubiquitous secondary metabolites of plants and their synthetic derivatives such as EMD 21388 interfere with hormone binding to transthyretin and activation by the selenoenzyme Type I 5'deiodinase. The resulting alterations of free thyroid hormone fractions in serum effect pituitary feedback regulation, hormone action and elimination. Selenium dependent regulation of expression of Type I 5'deiodinase and glutathione peroxidase was studied in the porcine kidney epithelial cell line LLC-PK1 at the enzyme activity, protein and steady-state mRNA levels. A cellular hierarchy of selenite utilization with preferential incorporation into Type I 5'deiodinase compared to glutathione peroxidase was found under limiting selenite supply. These mechanisms together with hierarchic selenium redistribution between brain and endocrine organs might contribute to maintain thyroid hormone homeostasis during development and pathophysiological situations. PMID- 1519445 TI - Characteristics of type III iodothyronine deiodinase. AB - Type III iodothyronine deiodinase (ID-III) catalyzes the inner ring deiodination of T4 to rT3 and of T3 to 3,3'-T2, representing an important pathway for the inactivation of thyroid hormone. High activities of this "oncofetal" enzyme are found in rat brain, skin and fetal intestine, rat and human placenta, chick embryo liver, monkey hepatocarcinoma cells, human colon carcinoma cells, and tadpole liver. ID-III shows substrate preference for T3 over T4; Km values are approximately 10-fold lower for T3 than for T4 but Vmax values are similar. In contrast to the marked ontogenic pattern of ID-III in different tissues, the enzyme shows little change under pathophysiological conditions, such as fasting and thyroid dysfunction. Brain ID-III activity is decreased in hypo- and increased in hyperthyroidism, but the changes are small. Reaction of brain and placenta microsomes with BrAc 125I-T3 results in extensive labeling of a 32 kDa protein (p32). However, the relationship of p32 with ID-III is not clear, since labeling of p32 is also observed in tissues without ID-III activity and is not inhibited with a large excess of substrate. PMID- 1519446 TI - The movement of thyroid hormones in the central nervous system. AB - Thyroid hormones in the central nervous system (CNS) present a number of complexities which include a marked difference in hormone effects on the developing brain compared to the mature brain, extensive regional heterogeneity within the brain, and alternate ways by which the hormones gain entry to the CNS and its cells. Furthermore, most of the T3 found within brain cells is derived from the T4 that they have accumulated. This brief review concerns the movement of the thyroid hormones as they leave the bloodstream and make their way into and through the CNS. There are many sites for potential control of thyroid hormone transport into the central nervous system. The blood brain barrier and the choroid plexus may work in tandem as two parallel resistors subjected to different controls to maintain brain interstitial levels of thyroid hormone at near constant levels. Thyroid hormone may enter neurons directly from the interstitial fluid or indirectly from the glial cells. Nonetheless, both neurons, perhaps at the synaptosome, and glial cells are capable of transporting and concentrating thyroid hormones at physiological levels. PMID- 1519447 TI - The role of transthyretin in the transport of thyroid hormone to cerebrospinal fluid and brain. AB - Cerebrospinal fluid (CSF) transthyretin (TTR), the main CSF thyroxine (T4) carrier protein in the rat and the human is synthesized in the choroid plexus (CP). After injection of 125I-T4 in the rat, radioactive T4 accumulates first in the CP, then in the CSF and later in the brain. We have shown that competitive inhibition of T4-TTR binding sites in the CP and CSF by a flavonoid results in a decrease in the radioactivity present in the brain after i.v. injection of 125I T4, suggesting that T4 transported to the CSF via the CP is a significant pathway for the supply of thyroid hormones to the brain. PMID- 1519448 TI - Cerebral expression of transthyretin: evolution, ontogeny and function. AB - This paper reviews studies on the synthesis and secretion of the thyroid hormone binding protein, transthyretin by the choroid plexus. The secretion of transthyretin by the choroid plexus into the cerebrospinal fluid may have an important function in the transport of thyroxine from the blood to the brain. The transthyretin gene is expressed in the choroid plexus of most vertebrates and synthesis of this protein may have evolved in the brain before the liver. PMID- 1519449 TI - Influence of thyroid hormone on brain gene expression. AB - Brain development in mammals is dependent on thyroid hormone. In the rat, the T3 receptor is present as early as the 14th day of fetal life and increases during the periods of neuroblast proliferation and oligodendrocyte differentiation. The mRNAs encoding the receptor isoforms can also be demonstrated by in situ hybridization, with different distribution of the alpha or beta forms. Expression of several genes was studied in hypothyroid animals during the neonatal period. The lack of thyroid hormone affects the expression of most oligodendrocyte genes in a time- and region-dependent fashion. The major role of thyroid hormone on myelin genes is on their timing of expression. Among the neuronal genes studied, thyroid hormone influences the expression of RC3, a brain specific gene encoding a protein kinase C substrate. Thyroid hormone is not require for the timing of expression of this gene, but is needed for its full expression both during the neonatal period and in adult animals. PMID- 1519450 TI - Thyroid hormone effects on neuronal differentiation during brain development. AB - Neurite outgrowth and acquisition of neuronal polarity depend on microtubule assembly and this process is impaired when hypothyroidism is established at late fetal stages in the rat. Taking in account these observations the effects of thyroid hormone deficiency in the developing cerebellum were studied with probes for different tubulin isoforms and for two microtubule-associated proteins, tau and MAP2, which are specific for the axons and the dendrites, respectively. The results showed that thyroid hormone deficiency: 1) desynchronizes the spatio temporal program of axonal and dendritic differentiation in the cerebellum. 2) Modifies the developmental pattern of expression of various tubulin isoforms. 3) Delays replacement of the immature tau variants by the mature forms. The adult variants of tau proteins specify adult and stable axons whereas the juvenile forms are expressed when axons are growing actively. According to these criteria the hypothyroid brain remains immature at stages when proper connectivity is normally established. Thyroid hormone appears therefore as an epigenic signal that synchronizes axonal and dendritic outgrowth, two major parameters of the construction of the neuronal network. PMID- 1519451 TI - Maternal hypothyroxinemia and brain development: I. A hypothetical control system governing fetal exposure to maternal thyroid hormones. AB - Maternal hypothyroxinemia consequent on endemic iodine deficiency is associated with an increased incidence of neurological disorders in the offspring. Such correlations were originally postulated as reflecting direct effects of elemental iodine on fetal brain development during early pregnancy, it being generally believed that maternal thyroid hormones do not cross the placenta in significant amount in consequence of the presence of elevated concentrations of TBG in maternal blood. However TBG possesses the capacity to enhance T4 transport to particular target organs during pregnancy. This realization led us to hypothesize a) that maternal T4 is transported to the fetus, and is of crucial importance to early fetal development, and b) that TBG forms part of a control system specifically designed to maintain at an optimal level the T4 environment to which the developing fetus is exposed. Subsequent studies in rats demonstrated that maternal T4 traverses the placenta in significant amounts prior to the development of the fetal thyroid. Other studies have led us to suggest that one or more isoforms of HCG may be implicated in a feed-back system interacting with the hypothalamic/pituitary system governing maternal thyroid hormone secretion. Though our experimental work has primarily focused on the effects of thyroid hormones on the fetal brain, we believe it to be likely that fetal exposure to maternal hormones is under placental control, and that other components of this putative system are worthy of study. PMID- 1519452 TI - Maternal hypothyroxinemia and brain development: II. Biochemical, metabolic and behavioural correlates. AB - Using a rat model, we have investigated the influence of maternal hypothyroxinemia throughout pregnancy on brain development in young and adult progeny. Although no consistent change was observed in whole brain total protein concentration, the subcellular distribution of protein was adversely affected. Isolation of glycoprotein from developing brain by concanavalin A-affinity chromatography and subsequent resolution by gel electrophoresis revealed the selective compromise of particular glycoprotein species. Furthermore, both control and experimental progeny expressed unique glycoprotein species which either persisted over the period studied or were transient. Calcineurin, a regulator of neurite elongation, was compromised in young progeny, as were a number of lysosomal enzymes (beta-D-glucosidase and aryl sulphatase). In adult progeny, the content of cerebroside sulphate (a major myelin galactolipid) was reduced in midbrain and paleocortex, and brain region-specific compromise was observed for acetylcholine metabolic enzymes. These changes were associated with alterations in behavioural output. We conclude that the availability of maternal thyroxine to the fetus may be a critical determinant for normal brain development and function. PMID- 1519453 TI - Regulation of T3 production in the brain. AB - Intracerebral thyroid hormone metabolism is responsible for maintaining intracellular T3 levels within narrow limits. A coordinated regulation of brain T4 to T3 conversion and T3 degradation allows the brain to respond to changes in the availability of circulating T4 and thereby isolates the brain from environmentally influenced changes in thyroid hormone status. T4 to T3 conversion is regulated by dynamic increases or decreases in the cellular content of the enzyme that catalyzes this reaction that are due to changes in enzyme degradation not enzyme synthesis. Little is known about the molecular events regulating the other deiodinating enzymes in the brain. In addition to the dynamic regulation of T4 to T3 conversion, anatomical segregation of the deiodinases that activate and inactivate thyroid hormone contributes to the minimal contribution of circulating T3 to the intracerebral pool of bioactive thyroid hormone. PMID- 1519454 TI - Psychomotor development in infants with congenital hypothyroidism diagnosed by neonatal screening. PMID- 1519455 TI - Mild iodine deficiency in fetal/neonatal life and neuropsychological performances. AB - The effects of mild/moderate iodine deficiency during the fetal/neonatal life on neuropsychological performances are still poorly defined. In this research we analyzed some parameters of cognitive performance with sensitive psychometric tests in children living in an area with moderate iodine deficiency. Each subject was submitted to the following neuropsychological tests: 1) a reaction time (RT) session, 2) the block design subtest of the WISC-R, 3) the coding subtest of the WISC-R. No significant difference was found between children with mild iodine deficiency and controls, for block design and coding tests. On the other hand controls had significantly faster RTs. Our data show that exposure to mild iodine deficiency in fetal/neonatal life does not affect general cognitive performance but influences the velocity of motor response to visual stimuli, which may be due to an alteration of the efficiency of the information processing mechanism. PMID- 1519456 TI - Intellectual assessment of hypothyroid children detected by screening. AB - The IQ was studied in 50 children with CH. Normal distribution of IQ was found in patients detected by neonatal screening. Close relationship was observed between subnormal IQ values (less than 90) and undetectable serum Tg levels (less than 0.3 ng/ml). The intellectual outcome in children with CH depends considerably from the intrauterine hypothyroidism. PMID- 1519457 TI - The possible etiological role of psychological disturbances in Graves' disease. AB - In the discussion of possible factors in the etiology of Graves' disease, stress has always played a major role. We investigated the possible influence of present depression (depressivity scale DS) and anxiety (State Trait Angstinventar STAI X1) on peripheral lymphocyte subpopulations in 10 patients with Graves' disease. The tests were done in hyperthyroidism and after 2-4 months in stable euthyroidism. Parallel to the psychometric testing, peripheral lymphocyte subpopulations were investigated. Elevated anxiety as a constant personality trait was investigated with the State Trait Angstinventar STAI X2 in 19 hyperthyroid patients with Graves' disease. 5 of the 10 patients had a pathological T4:T8 ratio and very high raw values for present anxiety (mean = 53,8; STAI X1), as well as a a high percentile for depression (median 93,1; DS). The other 5 patients with a normal T4:T8 ratio had much lower values for anxiety (mean = 37,8; STAI X1) and depression (median 78,4; DS). In those patients, the T4:T8 ratio remained normal in stable euthyroidism, while the values for anxiety and depression decreased. This also happened in the patients with a formerly pathologic T4:T8 ratio. However, the pathologic T4:T8 ratio persisted in those patients. The STAI X2 percentage ranking for the 19 hyperthyroid patients was 76,5. The value for healthy people is 55,5. Therefore a significantly elevated anxiety--representing a constantly elevated internal psychological stress--seems to be present in patients with Graves' disease. Since psychological stress is known to influence the immune system, such a constant personality trait could be a predisposing factor for Graves' disease.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1519458 TI - Integration of thyroid hormones with hypothalamic factors on pituitary TSH secretion. AB - A study employing a newly developed fourth generation immunometric serum TSH assay (assay limit 0.001 mu/l was performed to determine the temporal pattern of inhibition of serum TSH in response to a maximal suppressive dose of thyroid hormone (T3, T4 and TRIAC) as compared to the pattern produced by dopamine (DA) and dexamethasone (DEX). Mean onset of inhibition was 24, 48 and 68 minutes for thyroid hormone, DA and DEX, respectively. The inhibitory pattern was uniform and reproducible for the same or different individuals if data were normalized respective to basal TSH values. Inhibitory pattern with thyroid hormone formed two distinct log linear functions: A rapid phase (phase 1) spanning 48 minutes to 24 hours and a slower phase (phase 2) bridging 24 to 1,000 hours. A diurnal variation in phase 1, but not in phase 2 suppression, was observed. A phase 1 response was also produced by DA and DEX but not phase 2. Low dose TRH infusion studies indicated that thyroid hormone and DEX inhibited thyrotroph response at or beyond the TRH receptor, while DEX appeared to inhibit endogenous TRH secretion. No additive effects of DA or DEX on T3 inhibition were seen in phase 1. These studies provide new insight into the mechanism by which these endocrine factors complementarily regulate TSH secretion in man. PMID- 1519459 TI - Maturation of pituitary-thyroid function in the anencephalic fetus. AB - The recent availability of both cordocentesis and ultrasensitive/highly specific immunometric assays for TSH and its subunit determination along with direct "two step" assays for free thyroid hormone measurement, prompted us to study the maturation of hypothalamic-pituitary-thyroid axis in normal and anencephalic human fetuses from 17 to 26 weeks of gestation. In addition, TSH bioactivity was measured as cAMP accumulation in CHO cells transfected with recombinant human TSH receptor and TSH carbohydrate structure was studied by lectin chromatography. In both normal and anencephalic fetuses, circulating TSH and FT4 levels significantly increased from 17 to 26 weeks of gestation. Circulating FT3 concentrations were very low (0.5-3.1 pmol/l), while alpha-SU levels were very high (20-417 mg/l). Both FT3 and alpha-SU levels did not change from 17 to 26 weeks of gestation and, again, no differences between normal and anencephalic fetuses were recorded. Circulating TSH from both normal and anencephalic fetuses showed an enhanced bioactivity and was more retained on the lectin column than adult TSH, thus indicating that molecules with different carbohydrate structure are circulating during fetal development. In conclusion, the present data demonstrate that the absence of the hypothalamus does not compromise the maturation of pituitary-thyroid function and that the mechanisms underlying the secretion of TSH molecules with elevated bioactivity and different structure of glycosylated chains are not dependent on hypothalamic neuroendocrine control. PMID- 1519460 TI - Regulation of hypothalamic TRH production and release in the rat. AB - Thyrotropin-releasing hormone (TRH) is produced in the hypothalamic paraventricular nucleus (PVN) as a 255-amino acid precursor (pro-TRH) with 5 TRH progenitor sequences. Pro-TRH is enzymatically processed to yield TRH and other peptides, which are transported to the median eminence and released into hypophysial portal blood. To elucidate the role of TRH in the control of thyroid function, we studied hypothalamic TRH synthesis and release in many conditions. TRH synthesis and release were assessed by pro-TRH mRNA measurement, and by sampling portal blood or push-pull perfusate, respectively. Destruction of the PVN reduced TRH and TSH secretion dramatically, while electrical stimulation of this nucleus enhanced their release. Hence, the PVN is important for normal TSH secretion. TRH synthesis and release decreased in hyperthyroid rats, but increased in hypothyroid rats. The magnitude of these changes, however, was small compared with alterations in TSH, suggesting that the feedback of thyroid hormones on TSH release is mainly exerted at the pituitary level. TRH synthesis and release increased during cold exposure, and decreased during starvation and diabetes. Thus, altered thyroid function during cold exposure, diabetes and starvation seems due to modified hypothalamic TRH synthesis and release. PMID- 1519461 TI - Effects of selenium and iodine deficiency on iodothyronine deiodinases in brain, thyroid and peripheral tissue. AB - Long term nutritional selenium (Se) deficiency had only marginal effects on the thyroid T4 and T3 content and on the activity of the selenoenzyme type I deiodinase (5'D-I) in the thyroid gland. These findings reveal a remarkable resistance of the thyroid to Se-deficiency which may substantially contribute to the observed maintenance of T4 and T3 levels in circulating blood. In contrast to its maintained thyroidal activity, 5'D-I in peripheral tissues like liver and kidney was strongly decreased by Se-deficiency. The observed decrease of type II deiodinase (5'D-II) in the cerebral cortex of Se-deficient rats was obviously caused by the suppressing regulatory effect of elevated cortex T4 concentrations. The severalfold 5'D-II enhancement in iodine depleted animals was not abolished by additional Se-deficiency, suggesting that brain type II deiodinase is not a selenoenzyme. The role of selenium for cortex type III 5-deiodinase, which was moderately decreased in selenium as well as iodine-deficient rats, awaits definite evaluation by further studies. The different responsiveness to thyroidal and hepatic 5'D-I to Se restriction is further evidence for priorities in the selenium supply to different tissues. PMID- 1519462 TI - Radioimmunoassay of thyrotropin-releasing hormone in euthyroid subjects and in patients with thyroid diseases. AB - An episodic pattern of fluctuation in serum TRH level was demonstrated in euthyroid males. It is suggested that these rises in serum TRH-IR are due to its pulsatile hypothalamic release, however, it must be remembered that a high proportion of circulating TRH is derived from extrahypothalamic sources. The conception that the TSH surge during late evening is secondary to an increased TRH release could not be proved in the present study. In the euthyroid and primary hypothyroid groups the mean values of serum TRH-IR did not differ, while its level was slightly, but not significantly lower in hyperthyroid patients. The evaluation of a single TRH determination is impeded by the short half-life, low serum level and its production in extrahypothalamic sites, too. PMID- 1519463 TI - Monoamine regulation of prolactin and TSH secretion in hypothyroidism. AB - Dopaminergic and serotoninergic systems are involved in regulation of prolactin (PRL) and TSH secretion. About 10% of patients presented because of an galactorrhea and hyperprolactinemia (HP) have uncompensated primary hypothyroidism (PH). Two groups of patients were investigated using metoclopramide (MCP, DA antagonist, 10 mg i.v.), cyproheptadine (serotonin antagonist, 4 mg per os) and TRH tests. Group A consisted of 12 females with PH and hyperprolactinemia (HP). Group B presented 4 females with PH, HP and pituitary microadenoma on CT-scan. In control group of healthy euthyroid women basal PRL and TSH levels were in the normal range and statistically significant increase of both hormones was observed after MCP and TRH injections. Marked increase of basal TSH and PRL levels was found in both clinical groups. In contrast to control group no TSH reaction in MCP test was observed. PRL response to MCP was declined in group B versus group A. Cyproheptadine inhibited TSH secretion in patients with HP and PH, while this effect was absent in control group. TRH stimulated TSH and PRL response in group B was declined. Presented data shows that HP in PH may be due to the presence of subclinical microadenoma made manifest by hypothyroid state and/or due to disturbances in monamine control of PRL and TSH secretion. PMID- 1519464 TI - The pituitary control of rat thyroxine binding globulin. AB - Thyroxine-binding globulin (TBG) is in the rat a developmentally regulated protein, actively synthesized in postnatal developing pups and in aging animals, but undetectable in adults. Experimental depletion of thyroid hormones (TH) in adults by thyroidectomy (Tx) or by hypophysectomy (Hx) results in marked reexpression of TBG synthesis. T3 replacement in both cases antagonizes this effect, though only moderately in Hx rats. These observations point to a regulatory pathway of TBG synthesis common to TX and Hx rats, characterized by an inverse relationship between TBG and TH levels. However, along with this thyroid dependent TBG regulation, important differences between Tx and Hx rats are evidenced, pointing to specific pituitary factors of TBG control. The most striking difference concerns the effect of growth hormone (GH) replacement: the TBG of Tx rats is not affected, in contrast to that of Hx rats which is further increased by GH administration. The TBG response of the GH-treated Hx rats, which is strongly resistant to inhibition by T3, might involve deshomeostasis of GH controlled functions not necessarily linked to the thyroid, e.g. the pancreatic functions regulating carbohydrate or lipid metabolism. In the light of these studies, it may be envisaged that the high surge of rat TBG during postnatal development involves a transient sensitivity of the TBG gene to stimulation by endogenous GH, and that this sensitivity lasts until functional maturity of the hypothalamic-pituitary-thyroid axis has been achieved. PMID- 1519465 TI - Thyroid autoimmunity and neuropsychological development. AB - Thyroid autoimmunity may affect neuropsychological development by interfering with the fetal and/or neonatal thyroid status; indeed, both hypo- and hyperthyroidism during the fetal-neonatal life may be associated with a subsequent impairment of intellectual and psychomotor performances. Maternal thyroid status during early pregnancy, and in particular hypothyroidism due to autoimmune thyroiditis, can also affect the fetal neurological development. Finally, anti-thyroid drugs used to control hyperthyroidism in pregnant women with Graves' disease have been widely investigated for their possible effect on the intellectual development of the offspring. PMID- 1519466 TI - Antidepressants and thyroid hormone levels. AB - We assessed the effect of treatment with the tricyclic antidepressant, desipramine, on peripheral thyroid hormone levels in 28 severely depressed patients. Only those whose depression responded showed a decrease in their thyroxine levels without alteration of other thyroid function tests. In a second study involving 38 depressed patients, we observed an increased response to antidepressant treatment with the addition of triiodothyronine but not equivalent doses of thyroxine (T4). The finding is consistent with the decreases in plasma T4 levels which accompany an antidepressant response to desipramine. PMID- 1519467 TI - Thyroid hormones and depressive illness: implications for clinical and basic research. AB - It has been well-known for at least 100 years that both hypo- and hyperthyroidism may cause almost any psychiatric symptom, depending on the severity of the illness. No thyroid disorder, however, induces symptoms that are specific for a psychiatric disorder. Laboratory tests show depressed patients to be euthyroid. Any abnormalities that have been found, such as slightly elevated T4 levels or decreased T3 or TSH concentrations, have frequently failed to be replicated and do not fit any endocrinological diagnosis. They could reflect either "intervening factors" such as stress, methodological problems or a disturbance of central thyroid hormone metabolism. All antidepressant therapies (antidepressant drugs, carbamazepine, lithium, electroconvulsive therapy and sleep deprivation) have a marked influence on peripheral thyroid hormone levels. In particular, decreases in serum T4 and rT3 levels are often correlated to antidepressant response, suggesting that an effect on central thyroid hormone metabolism is involved in the as yet unknown mechanism of action of these therapies. Indeed, animal studies have shown that antidepressants do affect deiodinase activities and T3 and T4 concentrations in rat brain. However, the effects are highly area specific and dependent on the drug administered and the time of day at which the investigation was conducted. Although the mechanism of thyroid hormone action on CSF signal transduction is as yet unknown, effects on "general CNS functions" such as second messengers, G-proteins or calcium homeostasis seem more likely than specific effects on the different receptor systems. PMID- 1519468 TI - Single small CT lesions with seizures. PMID- 1519469 TI - Multimodal sensory and motor evoked potentials in a two-year follow-up study of MS patients with relapsing course. AB - Serial recording of multimodal sensory (pattern reversal visual, brainstem auditory, median and tibial somatosensory) and motor evoked potentials during a 2 year period was performed on a group of 25 patients with relapsing multiple sclerosis. A new, 10-degree evoked potentials abnormality scale was introduced. In contrast to the insignificant common trend of both the mean individual EP latency parameters and the mean expanded disability status scale and evoked potentials abnormality scale to deteriorate the changes in both expanded disability status scale (p less than 0.05) and evoked potentials abnormality scale (p less than 0.01) were significant using a 1-point criterion for change and non-parametric testing. Changes in both scales differed in about 50% of patients; contrary to bidirectional changes in the clinical scale, no improvement in the evoked potential scale was found. The introduction of an evoked potentials abnormality scale based on separate cut-off step-like criteria may increase the robustness of evoked potential changes due to the activity of the disease in longitudinal studies. PMID- 1519470 TI - Influence of caffeine, sweating and local hyperemisation on "Marstock" thermotesting. AB - Marstock thermotesting evaluates A-delta- and C-fiber functions. To optimize this method, intraindividual variations of vasodilatation, blood flow and sympathetic activity probably biasing thermotest results were imitated by exogenous stimuli which strongly exaggerated these intraindividual variations. In 20 healthy subjects, warm (WT), cold (CT), and heat-pain (HT) thresholds were determined in the morning at the thenar (th), the volar wrist (wr), and behind the malleolus internus (mi). Thresholds at the thenar and the volar wrist were compared with those during severe sweating induced by Minor's test, and to those measured when sympathetic activity had been increased by the ingestion of a high dose of caffeine (0.5 g). Furthermore, the intraindividual variation of local capillary blood flow and vasodilatation was imitated by a rubefacient liniment (Forapin) applied to the three sites. After a local hyperemisation had been induced thermal thresholds were measured and compared to those measured without any stimulation. Local hyperemia did not influence thermal thresholds significantly. Sweating only lowered cold thresholds at the thenar significantly and only slightly raised warm and heat-pain thresholds at the thenar. Caffeine significantly lowered warm thresholds and raised heat-pain thresholds at the thenar. To conclude, the tested exogenous interferences do not disturb thermal perception markedly, especially when testing is not performed at the thenar, but at the volar wrist and when the testing-procedure and parameters are standardised. PMID- 1519471 TI - Epilepsy and anomalies of neuronal migration: MRI and clinical aspects. AB - Neuronal migration disorders are the result of disturbed brain development. In such disorders, neurons are abnormally located. In diagnosing these conditions, magnetic resonance imaging is superior to any other imaging technique. This enables us to improve our knowledge of the clinical correlates of neuronal migration. With reference to migrational disorder, a retrospective study of all 303 patients with epileptic seizures referred for magnetic resonance imaging during a 3-year period was performed, 13 patients (aged 12-41, mean age 27) were identified. They represent 4.3% of the entire study group. Of the patients with known epilepsy, 6.7% and of the mentally retarded, 13.7% had migrational disorders. Four patients had schizencephaly as the dominant finding, one was classified as hemimegalencephaly, 2 had isolated heterotopias, and 6 had localized pachy- and/or poly-microgyria. The clinical pictures are complex. Ectopias of grey matter are recognised foci of epilepsy, but from an epileptological and a clinical viewpoint little attention has been given to these disorders. The present study shows that malmigration is not rare in epilepsy patients, especially not in the mentally retarded. PMID- 1519472 TI - Driving with Parkinson's disease. A controlled laboratory investigation. AB - The part played in traffic safety by illness or disability is unknown, as is the identity and degree of the disorders which necessitate the use of driving aids or completely incapacitate a person from driving. By means of a mock car, 28 persons suffering from Parkinson's disease were compared with 109 healthy controls. Only patients in presumed optimal drug regimen and without complicating disorders were included in the study group. The main results were failure to react to stimuli on several occasions, a high frequency of erroneous reactions in particular directional errors, reduced strength and speed of movement and increased reaction times. Typically the latter would entail a prolongation of the reaction distance with more than 1/3, i.e. 6 m when driving a car at a speed of 80 km/h. The Webster score proved to be an unreliable predictor of the results of the mock car test, and the UPDRS is suggested for future studies. PMID- 1519473 TI - Is the prevalence of Parkinson's disease in New Zealand really changing? AB - The prevalence of idiopathic Parkinson's Disease (IPD) in Dunedin, New Zealand on 31st July 1990 was 110.4/100,000. When corrected to a standard population based on the 1960 U.S. census, the prevalence fell to 76.0/100,000 due to changes in the age structure of the population. The corrected prevalence in Wellington (another New Zealand city), in 1962 was 99.6 (before the introduction of levodopa), and in Aberdeen, Scotland in 1984 was 102.7. The principal difference was fewer people under 65 years of age in our study. Case finding methods and diagnostic criteria were similar in all three studies, and case ascertainment was adequate. Under representation of younger people could be due to either a lower incidence rate or poorer survival due to treatment with high doses of levodopa compounds. Prospective research is required to explain our findings. PMID- 1519474 TI - A prospective double-blind clinical trial, comparing the sharp Quincke needle (22G) with an "atraumatic" needle (22G) in the induction of post-lumbar puncture headache. AB - Posture-dependent, post-lumbar puncture headache is most likely caused by continuous leakage of cerebrospinal fluid through the dura mater perforation with a consecutive downward sagging of the intracranial content and an irritation of pain-sensitive structures of meninges and blood vessels. A psychogenic co-factor may also play a role. It is generally acknowledged that the incidence and intensity of the headache correlate significantly with the diameter of the needles used. A second factor, the shape of the needle point plays a crucial role as is shown in our prospective, double-blind, clinical trial with 75 patients: employment of the "atraumatic" Sprotte needle with a rounded off point significantly reduced the incidence of post-puncture headache from 36% to 4%. Beside the discussion of pathogenic factors, remarks on a rational therapy are made. PMID- 1519475 TI - Effect of physical exercise on mortality in patients with Parkinson's disease. AB - Public health nurses visited and followed up for more than one year 438 patients with Parkinson's disease living in Osaka. The follow-up period averaged 4.1 years, during which 71 deaths were observed. The patients were classified according to the degree of physical exercise they performed, and the ratios of observed to expected deaths were calculated. The exercising group showed the lowest ratio of 1.68 (1.45 for patients able to walk independently, and 1.89 for those could not) while all patients exhibited a ratio of 2.47. Multivariate analysis using Cox's proportional hazard model, adjusted for age, sex, walking ability and duration of disease at study entry, showed that, compared with the exercising group, the non-exercising patients had a hazard ratio of 1.83. PMID- 1519476 TI - Vibratory stimulation increases and decreases the regional cerebral blood flow and oxidative metabolism: a positron emission tomography (PET) study. AB - The aim of this study was to examine the hypothesis, if the activation of some cerebral structures due to physiological stimulation is accompanied by deactivations of other structures elsewhere in the brain. A vibratory stimulus was applied to the right hand palm of healthy volunteers and the regional cerebral blood flow (rCBF) and regional cerebral oxygen metabolism (rCMRO2) were measured with positron emission tomography (PET). Regional analysis and voxel-by voxel plots indicated that the stimulation induced increases and decreases of the rCBF were coupled to increases and decreases of the rCMRO2. The increases were localized in the left primary somatosensory area (SI), the left secondary somatosensory area (SII), the left retroinsular field (RI), the left anterior parietal cortex, the left primary motor area (MI), and the left supplementary motor area (SMA). The decreases occurred bilaterally in the superior parietal cortex, in paralimbic association areas, and the left globus pallidus. The increases and decreases of the rCBF and rCMRO2 were balanced in such a way that the mean global CBF and CMRO2 did not change compared with rest. We conclude that the decreases of the cerebral oxidative metabolism indicated regional depressions of synaptic activity. PMID- 1519477 TI - Myasthenia gravis in Hong Kong Chinese. 2. Paediatric disease. AB - In a study covering 85% of the population of Hong Kong, 39% of all myasthenia gravis (MG) patients, i.e. 103 individuals (54 girls and 49 boys) were found to have had MG with onset before puberty. Two patients had transient neonatal MG, 20 had early onset juvenile MG and 81 had late onset juvenile MG. Restricted ocular MG occurred in 71% of patients and the remainder had generalised MG. The median age at onset was 4 years. Complete remission occurred in 34 patients (34%), a good response in 14 (14%), and fair response in 32 (32%). The clinical course remained static in 16 patients (16%) and 3 patients deteriorated. Two patients died, 1 with myasthenic crisis and the other with cholinergic crisis. All patients, except 2 with neonatal MG, were initially treated with anticholinesterase, but 24% also required steroid therapy. Thymectomy was performed for 12 patients, of whom 5 (42%) showed marked improvement. Thymic histology was normal in 3, showed hyperplasia in 6, non-invasive thymoma in 1 and involution in 2. The most commonly associated disease was Graves' disease which occurred in 7 patients (7%). PMID- 1519478 TI - Antibodies to Borrelia burgdorferi in patients with carpal tunnel syndrome. AB - In a study of 94 consecutive patients with neurophysiologically verified carpal tunnel syndrome (CTS) 7/94 had IgG and 0/94 IgM serum titers to Borrelia burgdorferi above the 98th percentile value of age and sex matched controls (n = 127). The difference in prevalence of positive IgG serum titers in patients, compared to controls, was not statistically significant. Even in patients, living in an area, highly endemic for Lyme borreliosis, routine serological screening for borrelia infection does not seem indicated in the investigation of CTS. PMID- 1519479 TI - Slowly progressive limb-kinetic apraxia with a decrease in unilateral cerebral blood flow. AB - We report two patients with slowly progressive motor disorders, whose principal manifestations were asymmetric limb-kinetic apraxia and muscle rigidity. In both patients MRI revealed no responsible lesion, whereas single photon emission computed tomography (SPECT) showed a decrease in cerebral blood flow (CBF) in the unilateral hemisphere. One patient with mainly right-sided apraxia had a decreased CBF in the left central region between the frontal and parietal cortices, and the other patient with left-sided apraxia in the right parietal cortex. In agreement with asymmetric clinical symptoms, the regional CBF decrease in the unilateral cortical areas including the frontal and parietal cortices may suggest a degenerative disease, presumably diagnosed as having cortico-basal degeneration. PMID- 1519480 TI - Dystrophin or a "related protein" in Duchenne muscular dystrophy? AB - Previously we have shown low levels of dystrophin immunoreactivity in muscle from patients with DMD. According to the "frame-shift hypothesis" DMD muscle should not synthesize any dystrophin through to the C-terminus and it has been suggested that the protein detected is not dystrophin, but a related autosomal homologue. We have labelled serial sections of DMD muscle with specific monoclonal antibodies to the amino, rod and C-terminal domains of dystrophin and find labelling on the same individual fibres, allowing us to conclude that the protein detected is Xp21-encoded dystrophin. This has an impact on the interpretation of myoblast transfer experiments. The abundance (on blots) of "C-terminal dystrophin" appears lower than "rod dystrophin" in both BMD and DMD. PMID- 1519481 TI - Systemic interferon-alpha in the treatment of HTLV-I-associated myelopathy. AB - Treatment with interferon-alpha (IFN-alpha) was undertaken in 16 patients with human T-lymphotropic virus type I-associated myelopathy (HAM). All patients had progressive spastic paraparesis before treatment. Twelve patients were enrolled in an open therapeutic trial with a dose of 3.0 x 10(6) IU/day of IFN-alpha and 4 in a randomized, double-blind, multidose (3.0 x 10(6), 1.0 x 10(6) or 0.3 x 10(6) IU/day) trial. IFN-alpha was injected intramuscularly for 28 days. Eight of 12 patients enrolled in an open trial and 2 patients receiving a dose of 3.0 x 10(6) IU/day of IFN-alpha in a randomized trial showed clinical improvements during and after the treatment. The results showed that, although not for all patients, systemic IFN-alpha with a dose of 3.0 x 10(6) IU/day is effective in the treatment of HAM. PMID- 1519482 TI - Evidence for an electrically silent, neurogenic fluid secretion in the rat jejunum in vivo. AB - The aim of this study was to evaluate the mechanism behind neurogenic fluid secretion in the rat jejunum. In vitro, short-circuit current (SCC) and potential difference (PD) were measured with the conventional Ussing technique. In vivo, electric parameters and net fluid transport (NFT) were simultaneously recorded with two different techniques. In separate in vivo experiments alkaline secretion (As) was estimated. In vitro, the chloride channel blocking substance 5-nitro-2( 3-phenylpropyl-amino)benzoic acid (NPPB) and the loop diuretic substance furosemide (F) inhibited SCC, whereas the carbonic anhydrase inhibitor acetazolamide (Ace) lacked effect. Noradrenaline inhibited SCC and this effect was antagonized by NPPB and F. In vivo, cholera toxin induced a parallel increase in PD/SCC and fluid secretion. Conversely, mesenteric nerve stimulation (MNS) or administration of the nicotinic antagonist hexamethonium (Hx), concomitantly inhibited PD/SCC and fluid secretion. However, there was a poor correlation between the magnitudes of these effects. F inhibited SCC in vivo and also the SCC effect of MNS. However, F had no effect on fluid secretion in vivo, nor on the NFT-effect of MNS. Jejunal As was stimulated by cholera toxin and MNS significantly inhibited As. The present results challenge the current view on the role of electrogenic chloride secretion in intestinal secretion. Alternative mechanisms are tentatively discussed. PMID- 1519483 TI - Contractions induced by angiotensin I, angiotensin II and bradykinin in isolated smooth muscle from the human detrusor. AB - In isolated human detrusor preparations angiotensin (At)II 10(-9)-10(-5) M caused concentration-dependent contractions. The contractile effect was immediate, and had an amplitude which at the highest concentration used, 10(-5) M, reached 103 +/- 16% of the mean contraction produced by K+ 124 mM (27.6 +/- 1.4 mN). The AtII effect was completely blocked by saralasin 10(-6) M, but was not affected by pre treatment of the preparations with captopril or enalaprilate. There was a marked tachyphylaxis to the actions of the peptide. AtI (10(-8)-10(-5) M) also caused contractions which were rapidly developing, and subject to a marked tachyphylaxis. At a concentration of 10(-5) M, the mean amplitude was 66 +/- 9% of the K(+)-induced contraction. The contractions were blocked by saralasin 10( 6) M, but not by captopril or enalaprilate 10(-5) M. In contrast, contractions produced by AtI in rabbit mesenteric arteries were practically abolished by the angiotensin converting enzyme (ACE) inhibitors. The contractions induced by both AtI and AtII were practically abolished after pre-treatment in a nominally calcium-free Krebs solution. However, blockade of L-type calcium channels by nifedipine 10(-6) M reduced the responses to both AtI 10(-6) M (by 38 +/- 4%) and AtII 10(-6) M (by 39 +/- 7%), but never abolished the contractions. Bradykinin (Bk; 3 x 10(-8)-10(-5) M) had a contractile effect in detrusor preparations which varied widely between strips. At a concentration of 3 x 10(-6) M, a maximum was reached amounting to 30 +/- 10% of the K(+)-induced contraction.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1519484 TI - Renal response to volume depletion and expansion in Milan hypertensive rats. AB - In previous studies on Milan hypertensive (MHS) rats, we found an impaired tubuloglomerular feedback (TGF) response before, during and after development of hypertension. In the present study MHS rats and rats of the Milan normotensive strain (MNS) were investigated after 24 hours of volume depletion (VD) and subsequently after 5% isotonic volume expansion (VE) with respect to whole kidney function, interstitial hydrostatic (P(int)) and oncotic (IIint) pressures, stop flow pressure characteristics of TGF and changes in early proximal flow rate in response to increased loop of Henle flow. MHS rats had higher mean arterial blood pressure (Pa) than MNS rats (129 vs. 101 mmHg) both after VD and after subsequent VE. No difference in glomerular filtration rate (GFR) was found. Both strains had a low urine flow rate (approximately 1.5 microliters min-1) during VD, which increased fourfold after VE. The interstitium was significantly more dehydrated in MHS, as indicated by a more negative net interstitial pressure (P(int)-IIint than in MNS (-1.3 +/- 0.3 vs. +/- 0.0 +/- 0.5 mmHg) after VE. The TGF mechanism was more activated in MHS during volume depletion, as indicated by a larger drop in stop-flow pressure (Psf) in response to loop of Henle perfusion (7.1 +/- 0.7 vs. 4.7 +/- 0.2 mmHg, P less than 0.05). However, during VD the loop of Henle flow that elicited half maximal response in Psf, the turning point (TP), was equally low in MHS and MNS (13.5 +/- 0.6 and 14.3 +/- 0.4, respectively).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1519485 TI - Effects on renal sodium and potassium excretion of vasopressin and oxytocin in conscious dogs. AB - Renal effects of arginine vasopressin and oxytocin were studied in conscious dogs, made water-diuretic by a waterload equivalent to 2% of body weight. Body water and content of sodium were maintained by separate servo-controlled infusions. Peptides were infused for 60 min at rates of 50 pg kg-1 min-1 (arginine vasopressin) or 1 ng kg-1 min-1 (oxytocin), either separately or combined. Infusions increased plasma arginine vasopressin to 1.9 +/- 0.2 (arginine vasopressin alone) and 1.8 +/- 0.3 pg kg-1 (arginine vasopressin plus oxytocin and plasma oxytocin to 72 +/- 5 (oxytocin alone) and 77 +/- 8 pg ml-1 (oxytocin plus arginine vasopressin). Arginine vasopressin or arginine vasopressin plus oxytocin increased urine osmolality similarly by a factor of 13, decreased urine flow to between 5 and 7% of control and decreased free water clearance. Oxytocin reduced urine flow and free water clearance and increased urine osmolality by a factor of 2. Oxytocin and arginine vasopressin separately increased excretion of sodium from 4 +/- 2 to 15 +/- 6 mumol min-1 and from 7 +/- 4 to 25 +/- 13 mumol min-1, respectively. Arginine vasopressin plus oxytocin led to a pronounced natriuresis (13 +/- 4 to 101 +/- 27 mumol min-1). Arginine vasopressin and arginine vasopressin plus oxytocin increased the excretion of potassium by a factor of 2.5. Oxytocin and arginine vasopressin plus oxytocin increased urinary Na+/K+ ratio by a factor of 3.7.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1519486 TI - Phenylephrine induces endothelium-independent rhythmic contraction in rabbit mesenteric arteries treated with ryanodine. PMID- 1519487 TI - Is autoregulation of cerebral blood flow in rats influenced by nitro-L-arginine, a blocker of the synthesis of nitric oxide? PMID- 1519488 TI - Different action of angiotensin II and noradrenaline on cytosolic calcium concentration in isolated and perfused afferent arterioles. PMID- 1519489 TI - Lev Zilber, the personality and the scientist. PMID- 1519490 TI - Cytotoxic T lymphocytes: specificity, surveillance, and escape. PMID- 1519491 TI - Cancer immunotherapy: are the results discouraging? Can they be improved? PMID- 1519492 TI - p53 expression in human breast cancer. PMID- 1519493 TI - Three years' experience with levonorgestrel-releasing intrauterine device and Norplant-2 implants: a randomized comparative study. AB - A randomized comparative study of levonorgestrel-releasing intrauterine device (LNG-IUD) and Norplant-2 implants was carried out in 200 women for 36 months. Three thousand one hundred woman-months of use were observed with each device. Only one pregnancy occurred in users of LNG-IUD at the 12th month of use. The change in bleeding pattern was the most frequent reason for discontinuation. The discontinuation rate for irregular bleeding with Norplant-2 was 17.3 and 26.8 at 24 and 36 months, respectively, as compared to 3.3 with LNG-IUD at both 24 and 36 months. The differences were statistically significant. Removal for amenorrhea and pain only occurred in acceptors of LNG-IUD. About 20-40% of women using Norplant-2 had prolonged bleeding through 36 months. The percentage of amenorrhea in LNG-IUD was the highest (29.3%) at the end of two years of use. More than 97% of subjects reported satisfaction with the methods used by themselves. PMID- 1519494 TI - Assessing potential demand for Norplant implants in Sri Lanka. AB - This study assesses potential demand for Norplant implants using data from a population-based survey conducted in rural Sri Lanka. Overall, 35% of currently married non-sterilized women of childbearing age expressed interest in using the implants, 52% did not want to use the method, and 13% were unsure about using it. The demand was substantially higher (44% vs 28%) among younger age groups (less than 30 years) than among older age groups (30-44). The results showed that life cycle variables (age, parity and marital duration) and fertility preference variables (desire for another child and desired birth-interval) were generally more important than socioeconomic variables in determining variations in potential demand for Norplant in Sri Lanka. Desired birth spacing was found to be a powerful indicator of the potential demand. The majority (85%) of respondents interested in using Norplant were also willing to absorb at least some of the cost of the implants. Among older age groups, those who were using modern temporary methods of contraception either exclusively or in combination with traditional methods had a higher demand for Norplant than non-users or exclusive users of traditional methods. For the younger women, however, potential demand did not vary significantly according to whether they were currently using a method or the type of method used. PMID- 1519495 TI - Changes in contraceptive practice in a multiracial urban-based community over a ten-year period. AB - There have been changes in the national policy regarding population growth in Malaysia from 1982. This report studies the changes in contraceptive practice among the three racial groups in this country, i.e. Malays, Chinese and Indians, over a 5-year period with an interval of 10 years. This is a retrospective study based on the attendance at the same family planning clinic in an urban setting. The striking change noted is the change in the racial composition of contraceptive usage in the two study periods with a shift from the Chinese being predominant in 1975-1979 to Malays in 1985-1989. There was no change among the numbers of Indians using contraception. The results also reveal a significant trend of change for users of the pill and those undergoing sterilization. There were no significant changes in IUD, condom and injectable usage. The study demonstrates how national policies, level of education and rural urban migration can significantly alter contraceptive practice. PMID- 1519496 TI - Clinical evaluation of quinacrine pellets for chemical female sterilization. AB - Under the auspices of the Coordinating Board of Indonesian Fertility Research (BKS PENFIN), a clinical trial was undertaken to examine the safety and effectiveness of the quinacrine pellet method for nonsurgical female sterilization. One hundred women were selected to receive 3 monthly insertions of 250 mg of quinacrine and were followed up at 1, 3, 6 and 12 months after the third insertion. Socioeconomic data and complaints and menstrual patterns at each insertion and every follow-up visit were recorded, as were all failures. The life table failure rate was determined to be 3.1. The continuation rate in this study was 96% at 1 year. Just over one-fifth of the women had amenorrhea by the third insertion, but most returned to normal by 1 year, and it appears that this amenorrhea was transient in nature. The method proved to be safe and effective, suggesting that larger clinical trials are in order. PMID- 1519497 TI - A New Zealand randomized comparative study of three IUDs (Nova-T, MLCu375, MLAgCu250): 1-, 2- and 3-year results. AB - A randomized comparative study was made in New Zealand of 3 models of copper IUDs, the Nova-T, MLCu375 and MLAgCu250, with interval acceptors. Completing 3 years of use, there were 608 Nova-T (14,011 woman-months), 586 MLCu375 (14,161 woman-months) and 596 MLAgCu250 (14,614 woman-months). At 3 years, loss to follow up was 5.2% for the Nova-T, 5.1% for the MLCu375 and 4.1% for the MLAgCu250. The Multiloads were significantly easier to insert and were preferred by the operators, as the insertion technique for the Nova-T was complicated. However, the Nova-T was significantly easier to remove. There was one perforation with a Nova-T in a puerperal breastfeeding woman. In the only 2 parameters that are comparable between series, accidental pregnancy and expulsion [1], the Multiloads have been shown to be superior with higher relevant continuation rates. At 3 years, the MLCu375 had a significantly lower accidental pregnancy rate and higher relevant continuation rate. The results obtained with the Nova-T are similar to those of the WHO study [2]. The MLCu375, with its potential for use up to 5 years, has been shown to be the superior device. PMID- 1519498 TI - A randomized comparative trial of the MLCu375, TCu220C, steel ring and uterine cavity-shaped IUDs. AB - The Stainless Steel Ring, Uterine Cavity-Shaped Device, TCu220C and MLCu375 IUDs were evaluated in a randomized trial of 1536 women in Guangdong Province, China. The first-year continuation and expulsion rates were significantly lower (p less than 0.05) for the latter 3 IUDs than for the Stainless Steel Ring. The first year pregnancy rates for the MLCu375 (0.76 per 100 women) and TCu220C (1.2 per 100 women) were significantly lower (p less than 0.05) than those of the other two devices (6.1 and 4.1 per 100 women). The results of the study show that the MLCu375 and TCu220C are the most suitable IUDs for women in Guangdong Province. PMID- 1519499 TI - The progestin-only oral contraceptive--its place in postpartum contraception. AB - The progestin-only oral contraceptive (POC) is not a widely-used method of contraception, possibly due to competition from other contemporary contraceptive methods or misunderstanding and prejudices among clients and/or service providers. Because of its underuse, the POC, as a contraceptive method, is under studied. This article evaluates the general merits of the POC and its disadvantages relative to combined oral contraceptives (COCs) and other contraceptive methods, specifically during the postpartum period and particularly for breastfeeding women. We find that the POC appears to be a safe and acceptable contraceptive method for postpartum women who are fully or nearly fully breastfeeding at six months postpartum or when menstruation returns. The POC could be considered for use at any time by non-breastfeeding postpartum women. The need for empirical studies of the POC is also discussed. PMID- 1519500 TI - [Aqueous protein concentration in diabetics. Report 5. Relationship between aqueous protein concentration and pathological findings of iridial vessels]. AB - The relationship between aqueous protein concentration (APC) and pathological changes in the iridial blood vessels was investigated in 49 eyes of 45 diabetic patients who underwent cataract surgery. APC was measured with a laser flare-cell meter before surgery. The quantification analysis method (type I, multivariate analysis) revealed that the most relevant factor to APC was the existence of nephropathy followed by, in descending order, the degree of retinopathy and changes in iridial vessels as demonstrated by electron microscopy. When data were reanalyzed after exclusion of the iridial vessels were found to be strongly relevant to APC. These results suggest that breakdown of the blood-retinal barrier contributes to the APC increase in eyes with advanced diabetic retinopathy, and that changes in iridial vessels may mainly influence APC in non- and milder-retinopathy groups. PMID- 1519502 TI - [Postoperative lens location calculated by ray tracing error correction (RTEC) in relation to axial length and corneal curvature]. AB - Postoperative lens location, defined as the distance between the posterior corneal surface and the loop-lens connection, was calculated by ray tracing error correction (RTEC) method. Parameters needed were the anterior corneal curvature and axial length before surgery; IOL power; shape factor; diameter; and postoperative refraction. Under the hypothesis that lens location is a linear function of axial length and corneal curvature, 72 X lenses (A hospital), 94 Y lenses (A hospital), 26 Z lenses (B hospital) and 32 W lenses (B hospital) inserted eyes were analyzed. Mean lens locations were 3.68, 4.28, 4.29 and 4.73 mm, respectively. Regression coefficients of the axial length were 0.291, 0.294, 0.212 and 0.189, respectively. Regression coefficients of the corneal curvature were -0.984, -0.921, -0.626 and -0.019, respectively. These results show that longer axial length or smaller corneal curvature has deeper postoperative lens location, and that the regression coefficients are similar if the hospital is the same and measuring instruments are the same. PMID- 1519501 TI - [Relationship of the office intraocular pressure (IOP) to diurnal fluctuation of IOP in low-tension glaucoma: a multivariate analysis]. AB - In 288 eyes of 114 low-tension glaucoma (LTG) patients, the mean, peak, trough and magnitude of the diurnal fluctuation of the intraocular pressure (IOP) determined over a period of 24 hours (diurnal IOP) were correlated with the IOPs recorded at the daytime office (office IOP), refraction, extent of visual field loss, age, sex, blood pressure and obesity index by the method of multivariate analysis. Only the mean office IOP was found to have a statistically significant contribution for estimating the mean, peak and trough of the diurnal IOP with the proportion (R) of 0.71 0.67 and 0.68 respectively. Furthermore, an analysis of the IOP data obtained from 118 LTG suspects using the receiver operating characteristics (ROC) curve showed that a patient whose peak diurnal IOP exceeds 21 mmHg could be detected with a sensitivity of 100% and a specificity of 46% if around-the-clock IOP measurements were carried out in patients whose mean office IOP are above 16 mmHg at least in one eye. In view of high prevalence of LTG in Japanese, estimation of mean diurnal IOP from mean office IOP and exclusion of primary open angle glaucoma using the mean office IOP of 16 mmHg as a cutoff IOP level are thought to be clinically useful. PMID- 1519503 TI - [Preretinal membrane in the macular area before and after the scleral buckling procedure]. AB - In 100 consecutive eyes with successful repair for rhegmatogenous retinal detachment, a prospective study was performed for preretinal membranes in the macular area by assessing before and after scleral buckling surgery. The preoperative prevalence of the preretinal membrane was 23% in the eyes with macula-on detachment, although not feasible in the eyes with preoperative macula off. After surgery, preretinal membranes were revealed in 59%, and macular puckers associated with retinal distortion were observed in 9%. Approximately half of the eyes without a preretinal membrane before surgery developed a postoperative preretinal membrane, suggesting that the preoperative preretinal membrane, which has been considered to be a remnant of the vitreous cortex, was not always necessary for the development of postoperative preretinal membrane. PMID- 1519504 TI - [Histopathological study of retinopathy of prematurity]. AB - Using light and electron microscopy, we studied the histopathological findings of retinopathy of prematurity (zone II, stage 3). The infant was born at 32-week gestational period and the birth weight was 1,255 g. He suffered from intracranial hemorrhage and hydrocephalus, and died at 78 days old. The ophthalmoscopic findings of both eyes at 72 days after birth showed that the intermedia was clear. The optic disc and posterior pole showed normal findings. Ridge formation with non-vascularized retina was seen at the equator of all quadrants of the fundus except the nasal quadrant of retina. Light and electron microscopic studies showed the following; in the most periphery of the vascularized retina, endothelial cell proliferation with the capillary lumen of glomeruloid tufts (rearguard) were seen. There were the aggregation of immature mesenchymal cells (vanguard) near to the rearguard. The cytoplasmic organelles of spindle cells in the non-vascularized retina were different from those of surrounding glial cell. Therefore, they were thought to be mesenchymal cells in the non-vascularized retina. Between the vanguard and the rearguard, the proliferative tissues composed of immature endothelial cells and mesenchymal cells extended into the vitreous body through the inner limiting membranes, and they formed the fibrovascular membranes on the retina. It was concluded that fibrovascular proliferation on the retinal surface in the active case of retinopathy of prematurity was composed of immature endothelial cells with vascular lumen and mesenchymal cells. PMID- 1519505 TI - [Clinicopathological and immunohistochemical study of malignant lymphoma of the orbit]. AB - The authors performed histopathological and immunohistochemical studies of 14 cases of orbital malignant lymphoma except for the conjunctival one. The patients were composed of 9 males and 5 females, and the average age of the cases was 61.5 +/- 12.3 years old. All cases were unilateral malignant lymphomas, 5 cases were right and 9 cases were left. Two patients had stage I disease, 10 patients had stage II disease, and 2 patients had stage III disease. The 5 year-survival rate was in 7/12 (58%). Histopathological examination revealed that 3 cases belonged to small lymphocytic, 4 cases diffuse small cleaved, 3 cases diffuse mixed and 4 cases diffuse large cell type by the working formulation. Immunohistochemical examination showed that all cases reacted positively against the B cell markers, while negatively against the T cell markers except for 1 case, indicating the cases were B cell lymphomas. Additionally, an immunoglobulin study contributed to elucidate the monoclonal proliferation of the tumor cells. PMID- 1519506 TI - [Quantitative analysis of the slow phase in congenital nystagmus during convergence]. AB - A previous report described that congenital nystagmus (CN) shows a lower intensity (frequency x amplitude) of spontaneous oscillation during convergence than for distance viewing. However, there has been no detailed report of quantitative analysis of the slow phase of CN during convergence. Therefore, in the present study, the slow phase of CN during convergence was analyzed in 7 patients horizontal and jerky type CN. The time constant of the slow phases were estimated using the repetitive non-linear least square method by a personal computer (NEC, PC 9801). The slow phases of CN for distance viewing were increasing-velocity exponentials, while those of CN during convergence were constant-velocity exponentials. The frequency, amplitude and mean velocity of the slow phase decreased during convergence. Thus, it was suggested that the velocity of the retinal image in CN decreased during convergence. PMID- 1519507 TI - [Quantitative analysis of eye movement during VDT work]. AB - The point of fixation during visual display terminal (VDT) work was analyzed by using Eye Mark Recorder-NAC with their corneal reflexes. The subjects were categorized into 2 groups, expert VDT worker and non-expert with VDT work. As for the VDT task, Japanese sentences were loaded. On the other hand, ordinary desk work copying was loaded using the same Japanese sentences. The following results were obtained. VDT work needed more complex eye movements in both vertical and horizontal directions compared with desk work. The point of fixation was mainly located on the surface of the oscilloscope in the expert subjects, whereas, it was mainly located on the keyboard in non-expert subjects. In analyzing the velocity of eye movements during VDT work, the expert moved the eyes more slowly than the non-expert. These results suggested that the VDT experts can move their eyes more effectively and slowly. PMID- 1519508 TI - [Motor adaptation in the Bielschowsky head-tilt test in cases of superior oblique palsy]. AB - To elucidate a motor adaptation phenomenon in the Bielschowsky head-tilt test in cases of superior oblique palsy, a gain of the otolith-ocular reflex was studied. The amplitude of ocular counter-rolling (OCR) of the non-paretic eye was measured with a photographic method, using limbal conjunctival marks as landmarks which were marked with indigo carmine. The average preoperative OCR of the non-paretic eye was 10.49 degrees at 30 degrees of head tilt to both sides, but after corrective surgery in the paretic eye the OCR of the non-paretic eye decreased to 8.43 degrees. To clarify the relation between OCR, duration of palsy and vertical deviation of the Bielschowsky head-tilt test (BHP), which was the difference of vertical deviation measured with the head tilted to the left and right shoulders at an angle of 30 degrees, the BHP/OCR ratio was calculated. We found no relation between BHP and OCR, but the BHP/OCR ratio increased proportionally in cases of long-standing palsy, From these results an increased BHP/OCR ratio could be an adaptive phenomenon caused by secondary innervational changes or muscle contracture to minimizing the contralateral head tilt to maintain binocular single vision. PMID- 1519509 TI - [A case of lamellar keratoplasty and autoscleroplasty combined with keratoepithelioplasty for Wegener's sclerocorneal ulcer]. AB - A 62-year-old man with Wegener's granulomatosis developed sclerocorneal ulcer. The general condition of the patient became well with steroid and presented cyclophosphamide therapy, he developed sclerocorneal ulcer. The sclerocorneal ulcer was present at the nasal limbus of the right eye. The ulcer was marked and presented descemetocele. Although lamellar keratoplasty was performed, the scleral ulcer recurred after two weeks. Excision of the affected sclera and autoscleroplasty was performed. The ulcer disappeared after 6 months, and the corneal graft was covered with corneal epithelium and conjunctiva. Ten months after autoscleroplasty was performed, a sclerocorneal ulcer was again recurred. We performed lamellar excision of the affected corneal area, resected the adjacent conjunctiva and performed keratoepithelioplasty. These surgical procedures were effective in preventing perforation of the cornea. Specular microscopic study of the corneal epithelium revealed nucleated epithelium and large epithelial cells. The endothelium appeared normal. PMID- 1519510 TI - [Eye movements]. PMID- 1519511 TI - [Experimental study on possibility of corneal injury by electromagnetic wave]. AB - The possibility of epithelial injury of BALB/C mice cornea exposed to a cathode ray tube (CRT) of a commercially available television was investigated. Epithelial injury of the cornea was confirmed by fluorescein-positive staining after 24 hours of CRT exposure approximately 3-9 cm from the surface of the CRT. The corneal epithelial injury was shown to be mainly limited to the most superficial layer by transmission electron microscope finding showing slight deterioration of the basal cell layer. The corneal epithelial defect was further measured by a scanning electron microscope in relation to the time of exposure to the CRT. The impaired area increased in dose-dependent manner to the some extent. The epithelial defect increased at 5 hours of CRT exposure and reached a maximum, that is 46.6% of the entire area of the cornea, by 12 hours of exposure, thereafter maintaining an equilibrium. The mechanism of corneal epithelial injury by CRT was discussed. PMID- 1519512 TI - [Ultrastructural, immunohistochemical and immunoelectron microscopic studies on the transitional part of the trabecular meshwork and the ciliary muscle in human and porcine eyes]. AB - The authors demonstrated the ultrastructure of the transitional portion of the human trabecular meshwork (TM) of the ciliary muscle (CM) by transmission electron microscopy, together with the porcine TM and CM, which have not been reported so far. In the transitional portion of the human eye, bundles of smooth muscle cells showed tapering in the anterior portion, and long slender processes of TM cells covered the outside of muscle bundles occasionally, in association with intervening nerve fibers. In the human transitional portion, there were many stick-like or irregular-shaped structures consisted of collagen fibrils. In the porcine eye, although the fine structure of the TM was similar to that of human TM, the shape of each porcine CM cell was irregular and their cytoplasm were invaginated into the adjoining cells, like herniation. In the immunohistochemical study, the positive immunoreactions were found in TM cells for vimentin, Schwann cells for S-100 and S-100b, and the CM cells for muscle (m)-actin and desmin in both species by using each antibody. Only the porcine TM cells were positive for S-100 and S-100b. In the human eye, smooth muscle-like cells similar to TM cells in the transitional portion were detected, and these cells were positive for m actin. Moreover, the cells covering Schlemm's canal were positive for factor VIII and UEA-1. These immune positivities were confirmed at the ultrastructural level. These immunohistochemical reactions may be useful tools to evaluate cell at the light and electron microscopic levels in human and porcine TM and CM regions. PMID- 1519513 TI - [Blood flow in the optic nervehead following intravenous administration of calcium antagonist]. AB - The authors quantitated the blood flow of the optic nervehead after intravenous administration of calcium antagonist. The hydrogen clearance method was used to measure the blood flow after placing an electrode sensor in the optic nervehead of 9 eyes of 5 Macaca fuscata monkeys, under general anesthesia by intravenous pentobarbital sodium. 5 micrograms/kg of nicardipine, a calcium antagonist, was rapidly injected into the femoral vein. Measurement of blood flow in the optic nervehead was started 5 minutes after injection until 90 minutes at intervals of 15 minutes. A dose of 2 micrograms/kg/min nicardipine was then administered intravenously for another 90 minutes. During the experiment, intraocular pressure was maintained at 15 mmHg under continuous monitoring of systemic blood pressure. The blood flow in the optic nervehead decreased to 83% 5 minutes after injection. It increased slowly and reached the initial value 50 minutes later. It reached 108% of the initial value 80 minutes after injection. During the additional infusion of nicardipine, the blood flow decreased slowly and reached 85% of the initial value. It is concluded that the blood flow in the optic nervehead changed depending on the method, quantity and duration after injection of intravenous calcium antagonist. The blood flow decreased immediately after administration. The main cause of this phenomenon was thought to be due to decrease of perfusion pressure secondary to decrease of systemic blood pressure. PMID- 1519514 TI - [Effects of timolol and carteolol on ocular pulsatile blood flow]. AB - Effects of timolol (0.5%) and carteolol (2%) on ocular pulsatile blood flow (PBF) were studied in healthy adult volunteers. PBF was measured with the BFA system, analyzing the ocular pressure waves. Each drug was instilled in one eye and PBF was measured in both eyes before and fifteen minutes after the instillation. In each drug, the PBF change between the two measurements was evaluated with a control study, which was performed in the same manner with physiological saline solution. In the non-instilled eyes, both timolol (n = 6) and carteolol (n = 9) had no significant change on PBF. In the instilled eyes, timolol (n = 6) caused no significant change, whereas carteolol (n = 9) increased PBF significantly. The range of the BFA system measurement error was within 4.7 +/- 2.4 microliters/min (P = 95%). Taking the error into account in each instilled eye, timolol (n = 6) increased PBF in 3 eyes and decreased it in 3 eyes, while carteolol (n = 9) increased PBF in 7 eyes, did not change it in one eye and decreased it in one eye. It is thought the effect of carteolol to increase PBF may be explained by endothelium-dependent relaxing factor (EDRF). PMID- 1519515 TI - [The effect of stimulus intensity and background luminance on the b-wave implicit time of photopic electroretinogram in normal human eyes]. AB - The authors studied the effect of stimulus intensity and background luminance on the b-wave implicit time of photopic electroretinogram in normal human eyes. Photopic electroretinograms were recorded at various stimulus intensities and background luminances in the range of 2.5 log scale using an integrating sphere of 30 cm diameter in the first experiment. The results from two normal eyes showed that with increasing stimulus intensity or with decreasing background luminance the b-wave implicit time of photopic electroretinogram prolonged and one or three wavelets superimposed on the ascending limb of the b-wave. The second experiment was performed using a half dome sphere of 60 cm diameter to study the b-wave implicit time at three different stimulus intensities. The results from 30 normal eyes disclosed a statistically significantly longer implicit time at the greater stimulus intensities. These results suggest that b wave implicit time in photopic electroretinogram becomes delayed with increasing stimulus intensity and becomes shorter with brighter background luminance. PMID- 1519516 TI - [Depth perception and amplitude of VEPs for variations of dot density in static random dot stereograms]. AB - Relative changes in depth perception and amplitude of VEPs were compared when the dot density in static random dot stereograms was altered. The maximum amplitudes of negative potentials evoked by either stereogram or uncorrelogram were recorded from the occipital region of human scalp. The peak latency was in the range of 160 to 260 msec, averaging 197 msec in 18 subjects. The amplitude of negative potentials evoked by either stereogram or uncorrelogram was always larger than that evoked by correlogram. The amplitudes on either stereograms, uncorrelograms or correlograms did not significantly increase when the dot density was increased, and there was no significant difference in amplitude on either stereogram or uncorrelogram. Depth perception did not closely correlate with the dot density nor with the amplitude of negative potentials. These results suggest that the amplitude of negative potentials may represent activities of disparity sensitive neurons elicited in a trigger feature manner, but it does not reflect activities of the higher order process of depth perception. PMID- 1519517 TI - [Electrophysiological experiment on neuronal pathway controlling horizontal eye head coordination in the cat]. AB - Tectal di-synaptic postsynaptic potentials (EPSPs) recorded in the abducens internuclear neurons (6 IN) were invariably facilitated by conditioning peduncular stimulation in the cat, which indicated that tectal and cortical excitation of 6 IN were mediated by a common set of interneurons. Using an extracellular recording technique, those common interneurons were identified as reticulospinal neurons by showing axonal projection to C2-3 spinal segment; they were also found to distribute mainly to the medial region of the nucleus reticularis pontis caudalis immediately rostral to the abducens nucleus, and not in the medullary reticular formation caudal to the abducens nucleus. The present experiment suggested that integration of tectal and cortical commands for horizontal eye-head coordination are taking place in the reticular formation rostral to the abducens nucleus which has been called the paramedian pontine reticular formation in the cat. PMID- 1519518 TI - Identification of viable myocardium by dipyridamole-induced improvement in regional left ventricular function assessed by echocardiography in myocardial infarction and comparison with thallium scintigraphy at rest. AB - In patients with coronary artery disease and left ventricular impairment, the distinction between ventricular dysfunction due to myocardial fibrosis and postischemic, viable, although dys-synergic, myocardium has important clinical implications. Experimental studies have shown that dipyridamole can increase myocardial function in stunned segments, outlining a potential role of dipyridamole-induced functional recovery as an ultrasonic marker of myocardial viability. The aim of this study was to assess whether the increase of regional left ventricular function early during dipyridamole infusion in basally asynergic segments could identify viable myocardium recognized by rest injected, delayed (greater than 14 hours from tracer injection) thallium and (in a subset of patients) late functional recovery evaluated by a follow-up echocardiogram at rest. Twenty-two patients with angiographically documented coronary artery disease and regional dysfunction in resting conditions (average left ventricular ejection fraction 43 +/- 8%) were studied by echocardiography. All patients underwent a dipyridamole-echocardiographic test (up to 0.84 mg/kg over 10 minutes) and a delayed planar thallium study. A 13-segment model was used for both techniques. A score index ranging from 1 (normokinesia) to 4 (dyskinesia) was used for echocardiography. Thallium-201 activity was expressed in each segment as the percentage of maximal activity in the corresponding view. After dipyridamole, the wall motion score was assigned to each segment in resting conditions and at peak hyperkinesia before possible mechanical signs of ischemia.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1519519 TI - Doppler echocardiographic patterns of left ventricular filling in patients early after acute myocardial infarction. AB - Diastolic function is routinely assessed using Doppler-derived left ventricular (LV) filling patterns. Ratios between peak flow velocities during early filling and atrial contraction (E/A) of less than 1 are considered pathologic and diagnostic of impaired relaxation. Myocardial stiffness can normalize the E/A ratio, and thus, in some clinical settings, a normal E/A ratio may identify patients with high filling pressures. LV filling patterns were studied with Doppler echocardiography in 15 healthy subjects and 38 patients with recent acute myocardial infarction. The results were correlated with clinical and hemodynamic variables. E/A ratio less than 1 was found in 14 patients (37%) and in only 1 control subject; E/A ratio greater than 2 found in 5 patients (13%) and in only 1 control subject; 19 patients (50%) had an apparently normal E/A ratio. No correlation was found between LV filling pattern and ejection fraction or presence of diabetes or arterial hypertension. LV end-diastolic pressures were low to normal in patients with an E/A ratio less than 1 and were usually greater than 15 mm Hg in those with normal or abnormally increased (greater than 2) E/A ratios. Thus, an apparently normal E/A ratio in patients after myocardial infarction may identify those with more severe LV diastolic dysfunction and increased LV filling pressure. PMID- 1519520 TI - Angiographic findings in the coronary arteries after thrombolysis in acute myocardial infarction. AB - The angiographic appearance of the coronary arteries was examined in 308 patients with acute myocardial infarction (AMI) who received high-dose intravenous thrombolytic therapy. Coronary angiography was performed on day 7 after admission to the hospital. Patients had an average of 2.4 discrete arterial narrowings or obstructions. The narrowings were proximal and related to bifurcations. Four fifths of the culprit arteries were patient; 104 (34%) had a ruptured plaque, 22 (7%) had an ulcerated plaque, and in 190 (62%) the lesions were eccentric. Patients differed from a comparable, previously studied, control series of 302 patients with chronic stable angina pectoris who had more extensive disease. They had 5.7 narrowings/patient, also located proximally and at bifurcations, but more widely distributed in the coronary tree. Patients with AMI who are suitable for thrombolysis have a unique coronary angiographic picture. The data confirm that AMI is caused by sudden rupture of a localized atheromatous plaque that initiates an obstructive thrombotic cascade. PMID- 1519521 TI - Analysis of the signal-averaged P-wave duration in patients with percutaneous coronary angioplasty-induced myocardial ischemia. AB - To assess the impact of angioplasty-induced myocardial ischemia on the duration of the surface P wave, patients undergoing elective angioplasty of isolated lesion in the left anterior descending, circumflex or right coronary arteries were monitored with a 3-channel electrocardiographic Holter system. The leads used were modified bipolar chest leads V5, aVF and V2 (CM-V5, CS-aVF and CM-V2). After echocardiographic signal-averaging, the earliest onset and the latest offset of the P wave were identified in all of the above time-aligned signal averaged leads, and the composite maximal P duration was measured under 10 x magnification. The maximal ST-segment shift during balloon inflation was also measured in all of the above leads at 60 ms after the J point. In the study group comprising 47 patients, the mean signal-averaged P-wave duration was 125.0 +/- 16 ms at baseline versus 130.0 +/- 15 ms during balloon inflation, p less than 0.005. In the left anterior descending coronary artery group (n = 23), the mean signal-averaged P-wave duration was 122.4 +/- 17 ms and 131.3 +/- 16 ms during balloon inflation, p less than 0.005). In the group with a right coronary artery lesion (n = 18), the values were 127.3 +/- 14 ms and 128.4 +/- 13 ms respectively (p = not significant). Significant increases in the P-wave duration were found to occur in groups both with (n = 34) and without (n = 13) ST-segment shift greater than or equal to 1 mm (both p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1519522 TI - Relation of high-density lipoprotein cholesterol and triglycerides to incidence of atherosclerotic coronary artery disease (the PROCAM experience). Prospective Cardiovascular Munster study. AB - The incidence of atherosclerotic coronary artery disease (CAD) was assessed in 4,559 male participants (aged 40 to 64 years) from the Prospective Cardiovascular Munster study, over a 6-year follow-up period. During this time, 186 study participants developed atherosclerotic CAD (134 definite nonfatal myocardial infarctions and 52 definite atherosclerotic CAD deaths including 21 sudden cardiac deaths and 31 fatal myocardial infarctions). Univariate analysis revealed a significant association between the incidence of atherosclerotic CAD and high density lipoprotein (HDL) cholesterol (p less than 0.001) and triglycerides (p less than 0.001). The relation to HDL cholesterol remained after adjustment for other risk factors. By contrast, the relation between the incidence of atherosclerotic CAD and triglycerides disappeared if, in a multivariate analysis by means of a multiple logistic function, cholesterol or HDL cholesterol were taken into account. However, the data suggested that hypertriglyceridemia is a powerful additional coronary risk factor, when excessive triglycerides coincide with a high ratio of plasma low-density lipoprotein cholesterol to HDL cholesterol (greater than 5.0). Even though the prevalence of this subgroup was only 4.3%, it included a quarter of all atherosclerotic CAD events observed. PMID- 1519523 TI - The case for unstable angina pectoris as a primary end point in primary prevention studies. AB - Coronary artery disease (CAD) primary end point definitions used in previous prevention trials are reviewed, as well as trends over time for CAD mortality, incidence and hospital discharges to see if new primary end points should be considered. CAD mortality has shown a dramatic decline in the U.S. in the last 20 years, whereas the decrease in the incidence of acute myocardial infarction (AMI) is less consistent. The decline in CAD incidence and mortality has been attributed to changes in lifestyle and increased medical/surgical intervention. Hospital discharge rates for CAD have risen during the past decade. In addition, although the rate of discharge for AMI appears to have stabilized, the rates for angina, and more dramatically for unstable angina, have increased. Unstable angina made up 4% of CAD discharges in 1980, and increased to 25% of CAD discharges in 1989. Because of these trends, future trials that rely solely on AMI as a primary end point will not reflect the actual experience with CAD presentation in the U.S. Given the greater availability of methods to diagnose unstable angina more accurately, and because of its high risk pathology, it is concluded that unstable angina should receive serious consideration as a primary end point in future primary prevention trials. PMID- 1519524 TI - Asymptomatic Cardiac Ischemia Pilot study (ACIP) AB - Ischemia can lead to myocardial necrosis, arrhythmias and death. Current practice suggests that asymptomatic or silent myocardial ischemia be treated as though it were symptomatic ischemia. This practice is associated with a growing trend of more frequent use of electrocardiographic monitoring, more complex therapeutic drug regimens and more frequent use of revascularization. However, there is no adequate study of the efficacy and safety of alternative therapeutic approaches to the treatment of asymptomatic myocardial ischemia. Therefore, the National Heart, Lung, and Blood Institute has planned the Asymptomatic Cardiac Ischemia Pilot (ACIP) study. The ACIP study is a multicenter international pilot trial to determine the efficacy and safety of angina-directed medical therapy, angina plus ambulatory electrocardiographic-directed medical therapy and revascularization. The treatment of asymptomatic cardiac ischemia is double-blind and placebo controlled. The primary end point is elimination of ischemia on the 48-hour electrocardiogram at 12 weeks. Patients will be followed-up for at least 1 year. Secondary analyses will include comparisons of the 2 medical regimens, amounts of medicine taken, and exercise versus electrocardiographic results. Eleven clinical units are recruiting 600 patients with coronary anatomy suitable for revascularization, a positive exercise stress test, and 1 or more asymptomatic ischemic episodes on the 48-hours electrocardiogram. Patients are stratified by center, symptom status and previous coronary surgery. If warranted by the pilot study results, a full-scale trial will be considered to determine whether amelioration of asymptomatic ischemia improves survival and reduces cardiovascular morbidity. PMID- 1519525 TI - Effect of high-current stimulation in patients with sustained ventricular tachycardia rendered noninducible by antiarrhythmic drugs. AB - Successful antiarrhythmic drug therapy for sustained ventricular tachycardia (VT) is presumed to be related to effects on myocardium within the re-entrant circuit. To test the hypothesis that prevention of VT induction may be related to effects on myocardium other than that directly involved in the tachycardia circuit, high current stimulation was used to achieve shorter coupling intervals in 22 patients with sustained uniform VT that was rendered noninducible by antiarrhythmic agents during stimulation at twice threshold. Sustained uniform VT was induced in 10 patients in response to high-current stimulation (group 1), including 4 tachycardias with the same morphology observed in the baseline study. There were no inducible arrhythmias in 12 patients (group 2). Patients were receiving several different antiarrhythmic regimens, but there was no particular drug associated with the induction of VT using high-current stimulation. There was no statistically significant difference between groups 1 and 2 in baseline VT cycle length (247 +/- 41 vs 253 +/- 44 ms), drug-induced increase in effective refractory period (20 +/- 15 vs 16 +/- 7%), QRS duration (25 +/- 10 vs 20 +/- 17%) or maximal current strength delivered (10.9 +/- 5.3 vs 9.3 +/- 4.0 mA). There was no significant difference in local activation with high-current stimulation between groups 1 and 2. In conclusion, sustained uniform VT was induced in 45% (10 of 22) of patients whose arrhythmias were rendered noninducible by antiarrhythmic agents during programmed stimulation at twice threshold.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1519526 TI - Reproducibility of programmed electrical stimulation responses in patients with ventricular tachycardia or fibrillation associated with coronary artery disease. AB - Invasive electrophysiologic studies were performed in 102 patients with sustained ventricular tachycardia (VT) or ventricular fibrillation (VF) using an aggressive programmed electrical stimulation (PES) protocol. The study was repeated after 2.0 +/- 2.9 days in all patients with no intercurrent changes in antiarrhythmic therapy. Patients with coronary artery disease (n = 72) were identified and PES results of these patients were analyzed and compared with results of patients without coronary artery disease. Multiple clinical and electrophysiologic factors were analyzed to determine any association with concordance of PES responses. No significant difference in concordance of PES responses was found in the 2 groups of patients. PES responses were groups into 3 categories: (1) noninducible, (2) nonsustained VT, and (3) sustained VT. Kappa values of PES responses of noninducible and sustained VT in both groups were higher and therefore the PES responses were more reproducible than nonsustained VT. The induction of sustained monomorphic VT was more reproducible than a PES response of nonsustained or sustained polymorphic VT. Inducible sustained VT with a rate of greater than or equal to 250 beats/min was less reproducible than induction of sustained VT with a rate less than 250 beats/min. Induction of VT by 3 extrastimuli was less reproducible than with any other mode. This short-term variability may account for false negatives associated with PES-directed antiarrhythmic therapy. Because of these findings, it is recommended that nonsustained VT and sustained polymorphic or rapid polymorphic VT should not be used as PES end points to guide antiarrhythmic therapy. PMID- 1519527 TI - Late ventricular arrhythmia and sudden death following direct-current catheter ablation of the atrioventricular junction. AB - Early reports of direct-current catheter ablation (DCCA) of the atrioventricular (AV) junction for resistant AV tachycardias documented efficacy of DCCA with little morbidity. Nine patients underwent DCCA at our institution 4 to 9 years ago: 3 patients had DCCA in the coronary sinus for permanent junctional reciprocating tachycardia, 2 patients had His ablation, 2 had coronary sinus and His ablation for permanent junctional reciprocating tachycardia, and 2 had DCCA for congenital tachycardia, and 2 had DCCA for congenital junctional ectopic tachycardia. Shocks (total 1 to 5) ranged from 12.5 to 400 J. Five patients had pacemaker implant at the time of DCCA. During follow-up, 3 patients developed clinical ventricular tachycardia: all 3 had DCCA of the His bundle. One asymptomatic patient with ventricular tachycardia, who had DCCA of the bundle of His, died suddenly 6 years later with ventricular fibrillation. Autopsy revealed 2 ventricular scars: 1 extending from the AV junction and 1 in the outflow tract. No patient with DCCA limited to the coronary sinus developed ventricular tachycardia. DCCA of the His bundle can result in late ventricular arrhythmias, possibly a result of extension of the DCCA lesion into the ventricle. These late findings should be considered in evaluating the safety and efficacy and follow-up for patients undergoing radiofrequency ablation. PMID- 1519528 TI - Reappraisal by transesophageal echocardiography of the significance of left atrial thrombi in the prediction of systemic arterial embolization in rheumatic mitral valve disease. AB - Systemic arterial embolization imparts a significant risk of serious complications throughout the lives of patients with rheumatic heart disease. Left atrial (LA) thrombi have been thought to be the major source of emboli. A transesophageal echocardiography (TEE) study of 260 consecutive patients with rheumatic mitral valve disease was performed during a period of 24 months, with particular reference to understanding the association between LA thrombi and embolic complications. Of these patients, 155 had predominant mitral stenosis, 24 had significant mitral regurgitation, and the remaining 81 with xenograft mitral valve replacement developed valvular dysfunction (25 resulted in predominant mitral stenosis and 56 in significant mitral regurgitation). LA thrombi were detected in 38 patients (group A) and absent in 222 (group B). Group A patients had a higher frequency of recent (less than or equal to 1 week before TEE study) and remote (greater than 1 week before) embolization than did group B patients (recent: 26.3 vs 5.4% [p less than 0.001]; remote: 18.4 vs 5.0% [p less than 0.01]). The frequency of atrial fibrillation was also greater in group A patients (100 vs 74.3%; p less than 0.001). The exclusion of patients with significant mitral regurgitation and sinus rhythm had no effect on the association between LA thrombi and evidence of previous embolization. It is concluded that TEE is a convenient diagnostic modality that can be used to identify a subset of patients with rheumatic mitral valve disease at high risk for systemic embolization. Consequently, preventive anticoagulation for possible embolic complications should be more vigorously adhered to in patients with rheumatic mitral valve disease and LA thrombi. PMID- 1519529 TI - Usefulness of left atrial and left ventricular chamber sizes as predictors of the severity of mitral regurgitation. AB - Left ventricular (LV) and left atrial (LA) chamber sizes are frequently used to assist in assessing the severity of mitral regurgitation (MR). To study the reliability of these measurements in the clinical setting 2-dimensional echocardiographic measurements of the left ventricle and left atrium were obtained in 92 consecutive patients with MR present on both angiography and Doppler echocardiographic examinations performed within 2.8 +/- 2.5 days of each other. The accuracy of chamber dimensions in identifying severe MR (angiographic grade 3 to 4+) was determined in the total population and the following patient subgroups: (1) isolated chronic MR with preserved LV function inclusive of all rhythms; (2) isolated chronic MR, preserved LV function and sinus rhythm; (3) isolated chronic MR with LV dysfunction; (4) chronic MR associated with other valvular disease; and (5) acute MR. Only in subgroup 2 were chamber sizes reliable in identifying severe MR. Atrial dimensions provided the most accurate assessment with an LA volume greater than 58 ml, anteroposterior dimension greater than 45 mm and superoinferior dimension greater than 55 mm, with sensitivities of 75, 75 and 88%, specificities of 83, 100 and 83%, positive predictive values of 92, 100, and 93% and negative predictive values of 56, 60, and 71%, respectively. LV dimensions had excellent positive predictive values but lower sensitivities. Normalizing for body surface area did not improve the accuracy of uncorrected dimensions. Although increased LA and LV dimensions can identify severe MR, smaller dimensions do not exclude this diagnosis. With acute MR, atrial fibrillation, LV dysfunction or associated valvular disease, these dimensions are not reliable. PMID- 1519530 TI - Pulmonary venous flow dynamics before and after balloon mitral valvuloplasty as determined by transesophageal Doppler echocardiography. AB - The pattern of left atrial filling was studied in 14 patients with severe mitral stenosis in sinus rhythm before and immediately after successful balloon mitral valvuloplasty by transesophageal pulsed Doppler echocardiography of the left superior pulmonary vein. Mean mitral valve orifice area increased from 0.8 +/- 0.1 to 2.2 +/- 0.3 cm2 (p less than 0.0001), and left atrial mean pressure decreased from 30 +/- 5 to 12 +/- 4 mm Hg (p less than 0.0001) after the procedure. After balloon mitral valvuloplasty, significant increases in peak systolic pulmonary velocity (35 +/- 16 to 44 +/- 10 cm/s; p less than 0.01), systolic flow velocity time integral (3.3 +/- 1.5 to 5.9 +/- 2.0 cm; p less than 0.001) and the ratio of systolic/diastolic pulmonary venous flow velocity time integrals (0.8 +/- 0.4 to 1.4 +/- 0.5; p less than 0.001) were observed. An acute increase in mitral valve orifice area caused no significant changes in peak diastolic forward flow velocity (40 +/- 7 to 41 +/- 9 cm/s; p = not significant [NS]), diastolic forward flow velocity time integral (4.3 +/- 1.7 to 4.6 +/- 1.8 cm; p = NS) and atrial flow reversal velocity (30 +/- 3 to 35 +/- 3 cm/s; p = NS) compared with at baseline. The results suggest that in patients with severe mitral stenosis and sinus rhythm, left atrial filling is biphasic with a diastolic preponderance, and successful mitral valvuloplasty is associated with an immediate increase in pulmonary venous systolic forward flow. PMID- 1519531 TI - Relation between extent of cardiac muscle cell disorganization and left ventricular wall thickness in hypertrophic cardiomyopathy. AB - The presence of numerous, abnormally arranged, cardiac muscle cells distributed widely throughout the hypertrophied left ventricular (LV) wall has been considered a characteristic, morphologic feature of patients dying of hypertrophic cardiomyopathy (HC) and also probably a determinant of impaired LV compliance. However, the relation between such regions of myocardial cell disarray and the magnitude of wall thickness in the same areas of the left ventricle has not been defined. Therefore, the present study was undertaken in which LV wall thickness and the percent area of myocardium disorganized were systematically compared in the same tissue section. No correlation was identified between wall thickness and the amount of myocardium disorganized in the same tissue sections, either when calculated separately for the ventricular septum, and anterolateral and posterior free walls, or when expressed for all 3 regions combined. Therefore, in patients with HC: (1) disorganized myocardial architecture is not confined to greatly thickened portions of the LV wall, but regions of the left ventricle with normal or only mildly increased thickness may also be disordered; and (2) whereas both LV wall thickening and cellular disorganization are manifestations of the primary cardiomyopathic process, these 2 morphologic features do not appear to be directly related with regard to their extent and distribution within the LV wall. These observations will potentially enhance understanding of the relation between LV structure and compliance in HC. PMID- 1519532 TI - Effect of an anterior wall motion abnormality on the results of single-plane and biplane left ventriculography. AB - Although the biplane area-length method would be optimal for all left ventriculograms, 2 contrast injections are needed in laboratories with single plane imaging equipment. The purpose of this study was to develop practical guidelines to identify the need for biplane left ventriculography in laboratories with single-plane equipment. From a retrospective analysis of 91 consecutive biplane ventriculograms (group 1), guidelines were identified that predicted when the ejection fraction calculated by the biplane method would differ significantly from the single-plane value. These guidelines were derived from information immediately available to the operator in the laboratory at the time of the procedure. Patients in group 1 were divided into 3 subgroups: biplane exceeding single-plane ejection fraction by greater than or equal to 0.05 (n = 20); single plane exceeding biplane ejection fraction by greater than or equal to 0.05 (n = 14); and ejection fractions within +/- 0.04 by the 2 methods (n = 57). By multivariate analysis, the only predictor of a higher ejection fraction calculated by the biplane method was an anterior wall motion abnormality. This finding was tested prospectively in a separate group of 60 patients (group 2). Left ventriculograms in group 2 patients were stratified before analysis by the presence or absence of an anterior wall motion abnormality. In patients with anterior wall motion abnormalities, the biplane ejection fraction was greater than the single-plane value by 0.05 +/- 0.04 (range -0.03 to +0.15). In contrast, this difference in patients without anterior wall motion abnormalities was -0.01 +/- 0.04 (range -0.09 to +0.06; p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1519533 TI - An improved method for adjusting the QT interval for heart rate (the Framingham Heart Study) AB - Several formulas have been proposed to adjust the QT interval for heart rate, the most commonly used being the QT correction formula (QTc = QT/square root of RR) proposed in 1920 by Bazett. The QTc formula was derived from observations in only 39 young subjects. Recently, the adequacy of Bazett's formula has been questioned. To evaluate the heart rate QT association, the QT interval was measured on the initial baseline electrocardiogram of 5,018 subjects (2,239 men and 2,779 women) from the Framingham Heart Study with a mean age of 44 years (range 28 to 62). Persons with coronary artery disease were excluded. A linear regression model was developed for correcting QT according to RR cycle length. The large sample allowed for subdivision of the population into sex-specific deciles of RR intervals and for comparison of QT, Bazett's QTc and linear corrected QT (QTLC). The mean RR interval was 0.81 second (range 0.5 to 1.47) heart rate 74 beats/min (range 41 to 120), and mean QT was 0.35 second (range 0.24 to 0.49) in men and 0.36 second (range 0.26 to 0.48) in women. The linear regression model yielded a correction formula (for a reference RR interval of 1 second): QTLC = QT + 0.154 (1-RR) that applies for men and women. This equation corrects QT more reliably than the Bazett's formula, which overcorrects the QT interval at fast heart rates and undercorrects it at low heart rates. Lower and upper limits of normal QT values in relation to RR were generated.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1519534 TI - Reversal of human platelet aggregation by low concentrations of nitroglycerin in vitro in normal subjects. AB - The potential reversal of platelet aggregation in vitro by nitroglycerin in low concentrations was explored using both optical aggregometry and electron microscopy. Venous blood was collected from a cohort of normal volunteers (20 men and 10 women) aged 21 to 65 years. Aggregation in platelet-rich plasma was induced by adenosine diphosphate in concentrations just sufficient to maintain a steady state of aggregation, without a spontaneous disaggregation phase (3.5 to 5 microM). Administration of nitroglycerin after the induction of aggregation caused both inhibition of the primary wave of developing aggregation and marked disaggregation. This combined effect was maximal when nitroglycerin was added at 0.5 minute after the beginning of aggregation. The observed reversal of platelet aggregation by nitroglycerin was concentration-dependent. Significant effects occurred with nitroglycerin concentrations greater than or equal to 10(-8) M. Concentration associated with 50% reversal of aggregation was 1.52 +/- 0.24 (SEM) x 10(-6) M. Electron microscopy revealed that 10(-6) M nitroglycerin induced a significant reduction in both platelet clumping and morphologic changes associated with aggregation. The results of the current study suggest a beneficial antiplatelet effect of nitroglycerin in restoring homeostasis in the face of incipient platelet aggregation. The clinical use of nitroglycerin in patients with acute ischemic syndromes may rest on this action. PMID- 1519535 TI - Fascicular blocks: not interpretable from the electrocardiogram. PMID- 1519536 TI - Low high-density lipoprotein cholesterol and what to do about it. PMID- 1519537 TI - Cardiac transplant recipients are sex blind to their heart donors. PMID- 1519538 TI - Incidence and prognostic significance of chronic atrial fibrillation among 5,839 consecutive patients with acute myocardial infarction. The SPRINT Study Group. Secondary Prevention Reinfarction Israeli Nifedipine Trial. PMID- 1519539 TI - Prevalence of pseudoischemic ST-segment changes during ambulatory electrocardiographic monitoring. PMID- 1519540 TI - Differentiation of ventricular tachycardia from ventricular fibrillation using intraventricular electrogram morphology. PMID- 1519541 TI - Effects of severe pulmonary hypertension on outcome of balloon mitral valvotomy. PMID- 1519542 TI - Relation of exercise capacity in dilated cardiomyopathy to left atrial size and systolic function. PMID- 1519543 TI - Circadian rhythm of pulmonary embolism in patients with acute spinal cord injury. PMID- 1519544 TI - Dimensions of the triangle of Koch in humans. PMID- 1519545 TI - Does delayed loss of preexcitation after unsuccessful radiofrequency catheter ablation of accessory pathways result in permanent cure? PMID- 1519546 TI - Coronary spasm and cardiac arrest after coronary arteriography in unsuspected thyrotoxicosis. PMID- 1519547 TI - Superficiality of femoral artery pseudoaneurysm as a risk factor for rupture. PMID- 1519548 TI - Simultaneous mechanical clot fragmentation and pharmacologic thrombolysis in acute massive pulmonary embolism. PMID- 1519550 TI - Left ventricular function in myasthenia gravis. PMID- 1519549 TI - Rapid breakdown during exposure to daylight of molsidomine when administered by continuous intravenous infusion. PMID- 1519551 TI - Death in opera: a case study, "Tales of Hoffman"--Antonia. PMID- 1519552 TI - Effect of acupuncture at right Hoku point on the bilateral vibration-induced finger flexion reflex in man. AB - Vibration applied to the volar side of the finger tip has been reported to induce finger flexion reflex. Acupuncture is reported to inhibit this vibration-induced finger flexion reflex (VFR) in the ipsilateral hand. The purpose of this study was to investigate the effect of unilateral acupuncture in the hand on VFR in both hands. As no systematic study on the relationship between VFR and the force of voluntary contraction with no vibration (Initial Force: IF) has been reported, this relationship was studied prior to the present study on acupuncture. VFR was induced by mechanical vibration on the volar side of the middle finger tip with 10 g to 500 g IF. With approximately 300 g IF, VFR was consistent. Therefore, approximately 300 g IF was applied for VFR induction to study the effect of acupuncture on VFR. A stainless steel needle was inserted into the right Hoku point and remained inserted (in-situ technique) for 10 minutes. VFR in both hands was significantly decreased by acupuncture at the right Hoku point (% control force of VFR: right, 67.8%; left, 74.6%). The present results suggest that acupuncture in the unilateral hand influences the bilateral reflex arc of VFR. PMID- 1519553 TI - The pharmacological and pathological studies on Taiwan folk medicine (VII): The anti-inflammatory effect of Echinops grjiisii. AB - The hepatotoxic-protective effects of "San-fang-feng" (the root of E. grijisii) and "Lou-lu" (the root of E. latifolius) on CCl4 induced hepatotoxicity have been proposed in our previous paper (Lin et al, 1990). The anti-inflammatory effects of these two crude drugs were investigated in this experiment. The results indicated that both of them displayed pronounced anti-inflammatory activities against carrageenan-induced edema. Furthermore, in order to isolated the main active components of E. grijisii, fractions obtained from the methanolic extract of E. grijisii were investigated in mice for their 24-h LD50 and 95% confidence limits, which could be used as a guiding for further animal experiments. Our findings demonstrated that n-hexane (100,300 mg/kg), chloroform (30,100, 300 mg/kg) and ethyl acetate (30,100, 300 mg/kg) fractions could markedly inhibit the carrageenan-induced inflammation, and the main active principle was found to be concentrated in the chloroform fraction, which possessed significant inhibitory activities even more than does indomethacin. PMID- 1519554 TI - The pharmacological and pathological studies on Taiwan folk medicine (VIII): The anti-inflammatory and liver protective effects of "mu-mien". AB - The bark, xylem of stem, and root of (1) Bombax malabarica DC. and (2) Ceiba pentandra GAERTN. are marked as "Mu-mien" in Taiwan. In order to clarify the pharmacological effects of these three parts, anti-inflammatory and liver protective effect were evaluated with carrageenan-induced paw edema and CCl4 induced hepatotoxicity in rats. The statistical analysis (ANOVA) shows that all of the treatment used exhibited significant anti-inflammatory activity against carrageenan-induced edema. Furthermore, the administration of root and xylem of stem of B. malabarica showed the activity even better than indomethacin group did. However, only three used parts of B. malabarica significantly alleviated liver injury induced by CCl4. Meanwhile, the histological changes in rat hepatic tissues such as fatty change, ballooning degeneration, cell necrosis, lymphocytes and Kupffer cells were also observed. PMID- 1519555 TI - Cardiovascular effect of a senso (toad venom) - containing drug in anesthetized dogs (2): Influence of propranolol. AB - Effects of a Senso (toad venom)-containing drug KY on systemic hemodynamics were examined, and participation of beta-adrenoceptor in its action was evaluated by using propranolol in anesthetized dogs. KY produced a positive inotropic action, and decreased total peripheral (TPR) and coronary vascular resistances (CR), while renal vascular resistance (RR) was increased. After propranolol, KY significantly increased TPR, CR, vertebral vascular resistance and RR. KY-induced positive inotropic action was partly diminished but not abolished by beta blockade. These results indicate that the beta-adrenergic action may be involved in the vasodilating effect of KY and partly in the positive inotropic action. PMID- 1519556 TI - The hormonal response to HCG stimulation in patients with male infertility before and after treatment with hochuekkito. AB - To investigate the changes in responsiveness to hCG stimulation, and the effects on sperm qualities and basal hormone levels, 63 infertile men received 7.5qr of Hochuekkito daily for 3 months (1). Sperm density (p less than 0.01) and motility (p less than 0.01) were significantly increased after the treatment (2). Serum prolactin (p less than 0.01) and estradiol (p less than 0.01) levels were significantly decreased after the treatment (3). Enhanced responsiveness of testosterone (p less than 0.05) and estradiol (p less than 0.05) excretion to hCG injection were observed in patients with oligoasthenoteratozoospermia. These results suggested that Hochuekkito corrected Leydig cell dysfunctions in some infertile men, resulting in improvements in sperm qualities. PMID- 1519557 TI - Inhibitory effect of ginsenosides on migration of arterial smooth muscle cells. AB - Migration of arterial smooth muscle cells (SMC) in the arterial wall plays an important role in the formation of intimal thickening of atherosclerotic lesions. In this study, we examined the effect of ginsenosides on SMC migration induced by platelet-derived growth factor (PDGF) and SMC-derived migration factor (SDMF). Ginsenosides had inhibitory effects on SMC migration and the striking effects were observed with ginsenoside-Rb2 and -Rc in a dose-dependent manner. These results suggest that the administration of ginsenosides on the patients may prevent intimal thickening, in part, by inhibiting SMC migration in the arterial wall. PMID- 1519558 TI - Effects of tokishakuyakusan, keishibukuryogan, shakuyakukanzoto and unkeito on ovarian endothelin, renin and angiotensin II in pregnant mare's serum gonadotropin-treated immature rats. AB - We have previously proposed the ovarian ERAANPS (endothelin-rein- angiotensin atrial natriuretic peptide system). The present study was undertaken to examine in vivo the effects of herbal medicines [Tokishakuyakusan (TS), Keishibukuryogan (KB), Shakuyakukanzoto (SK) and Unkeito (UT)] on endothelin-1 (ET), renin and angiotensin II (A II) in the ovaries, of immature rats treated with 10 IU PMS for 48 h. ET and all components of renin-angiotensin system (RAS) were found at high levels in the ovary. Concomitant treatment with PMS plus TS, KB, SK or UT, especially TS and UT, tended to decrease the ET levels in ovary, while components of RAS tended to increase. However, ET, renin and A II levels in plasma were not at all affected after treatment with TS, KB, SK or UT. These results suggest that TS, KB, SK or UT may regulate the ovarian ERAANPS. PMID- 1519560 TI - Comments on nomenclature in traditional Chinese medicine. AB - The present article suggests that the nomenclature used in traditional Chinese medicine is currently unclear resulting in improper usage of terms and subsequent confusion. This paper is an attempt to clarify this nomenclature confusion. Traditional medicine of China should be called "traditional Chinese medicine" (T.C.M.) rather than the frequently used "Chinese medicine". The latter term fails to express the "tradition" associated with T.C.M., and also it does not distinguish between T.C.M. and modern Chinese medicine. "Oriental medicine", another frequently used term for T.C.M., has the same kind of shortcomings. The true colors of T.C.M. should be restored. The author also notes that "herb", "herbology" or "herbal medicine" is not synonymous with traditional Chinese materia medica. Herbal medicine is a type of folk medicine whereas traditional Chinese materia medica is a formal branch of traditional Chinese medicine. Furthermore, the author suggests that "acupunctology" be used when referring to the science of acupuncture whereas "acupuncture" should be used with reference to a method or perhaps the therapy of needling. PMID- 1519559 TI - Alterations of pulse by Chinese herb medicine. AB - Rats were injected with the crude extract of Chinese herbs, Rhizoma Coptidis, Radix Bupleuri and Cinnamomum cassia Blume. The pulse of the tail artery were examined. The results indicated that each drug had a specific effect on the Fourier components of the pulse. PMID- 1519561 TI - In the best tradition, physicians volunteer. PMID- 1519562 TI - 24-h pH monitoring for gastroesophageal reflux disease: already standard but not yet gold? PMID- 1519563 TI - Rationing medicine: hard choices in the 1990s. PMID- 1519564 TI - Targeted colon cancer screening: a concept whose time has almost come. AB - Screening of large populations for colon malignancy has been advocated in several countries to detect cancers at earlier, curable stages and/or prevent cancer by detecting and removing premalignant polyps. Ideal screening would identify subjects with the highest risk of cancer and target sensitive screening tests at this population. Recent data suggesting that environmental factors and genetic alterations contribute to increased cell proliferation in colonic mucosa provide several avenues for identification of high-risk subjects. This review examines the current literature regarding colon cancer risk factors, focusing on new ways to identify individuals who may benefit from targeted screening. PMID- 1519565 TI - Scintigraphy in gastroesophageal reflux disease: a comparison to endoscopy, LESp, and 24-h pH score, as well as to simultaneous pH monitoring. AB - We compared scintigraphy to other reflux tests in 45 symptomatic patients. Sensitivity of 24-h pH score was 82%, endoscopy 64%, and LESp 33%. Scintigraphy was insensitive (36%), although 50% of patients with esophagitis had a positive test. Specificity and positive predictive value were good (all greater than or equal to 88%) in discerning patients with an abnormal 24-h pH score and esophagitis. We suggest scintigraphy as the first diagnostic test to confirm frequent reflux events (REs) and normal clearance in the subgroup of patients with severe endoscopic esophagitis, and manometry and 24-h pH monitoring when scintigraphy is negative. We also compared scintigraphy to simultaneously performed pH monitoring in detecting individual postprandial REs and their clearance. The two methods agreed in only 25% of total reflux events. Scintigraphy was superior at detection of reflux of buffered gastric contents and detection of additional REs during acid clearing intervals, whereas only the pH probe detected REs after gastric emptying. We conclude that scintigraphy has a limited role as a diagnostic test in gastroesophageal reflux disease, and much potential as a research tool, especially in combination with the pH probe. PMID- 1519566 TI - Ambulatory 24-h esophageal pH monitoring: normal values, optimal thresholds, specificity, sensitivity, and reproducibility. AB - Ambulatory 24-h esophageal pH monitoring is increasing in popularity as the means to measure esophageal exposure to gastric juice and document the presence of gastroesophageal reflux disease, particularly before surgical therapy. Normal values for pH exposure were obtained from 50 asymptomatic healthy subjects. Receiver operating characteristic curves constructed from another 25 asymptomatic healthy subjects and 25 selected patients with other markers of increased esophageal acid exposure showed that a composite score and the percent total time pH less than 4 provide the most efficient interpretation of the test with a sensitivity of 96%, a specificity of 100% and an accuracy of 98% for the composite score, and a sensitivity, specificity, and accuracy of 96% for the percent total time pH less than 4. Repeat monitoring of healthy volunteers and symptomatic subjects in the inpatient and outpatient environment showed no significant difference, with the exception that the number of reflux episodes was significantly greater during the outpatient recording in volunteers. This did not affect the clinical accuracy of the test. Esophageal pH probes were well tolerated, but caused belching and coughing during the early part of the monitored period. We conclude that computerized ambulatory 24-h esophageal pH monitoring in the outpatient setting provides accurate and reproducible results. PMID- 1519567 TI - Esophageal perforation: an 8-year review of a multispecialty clinic's experience. AB - Esophageal perforation is the most serious perforation of the gastrointestinal tract, and despite early diagnosis and treatment, mortality remains high. Twenty four cases of esophageal perforation seen at a large multispecialty clinic between 1983 and 1991 were retrospectively reviewed. Thirteen patients presented with acute perforation, five with subacute, and six with chronic perforation. Eighteen (75%) of 24 perforations resulted from iatrogenic causes, and the rest were spontaneous. Of the iatrogenic perforations, therapeutic endoscopy and paraesophageal surgical complications were responsible for 55% and 33%, respectively. Chest pain, fever, and dyspnea were common presenting signs and symptoms of acute perforation, whereas dysphagia and supraventricular arrhythmia were more prominent features of chronic perforation. All but seven patients had surgical intervention. An overall mortality rate of 46% was noted, and despite early diagnosis and treatment, this mortality was associated with the severity of underlying disease. PMID- 1519568 TI - Increased incidence of gallstones and prior cholecystectomy in patients with large bowel cancer. AB - In a retrospective study, the frequency of occurrence of gallstones and cholecystectomy in 479 patients with colorectal cancer was compared with that of 483 matched control patients with other malignancies. The mean interval between cholecystectomy and colon cancer diagnosis was 15.1 +/- 9.9 yr (range 2-53 yr), and there was no statistically significant difference, compared with the control group at 13.9 +/- 8.2 yr (range 2-31 yr). In patients with colon cancer, the general increased relative risk of concomitant diagnosed gallstones (relative risk 1.73, p = 0.0123) and the relative risk of cholecystectomy (relative risk 2.08, p = 0.0074) was statistically significant. However, when the data with regard to sex were analyzed, significant differences were observed only in women. Women affected by right colon cancer also had a statistically significant higher incidence of previous cholecystectomy (relative risk 2.86, p = 0.0096), but no significantly higher incidence of concomitant gallstones. The general increased relative risk in patients with right colon cancer and decreased risk in patients with left colon cancer of concomitant gallstones and prior cholecystectomy was statistically significant. Our data provide evidence for the hypothesis that both gallstones and cholecystectomy increase the general risk of large bowel cancer. Therefore, they are also compatible with the possibility that common risk factors causes the association between gallstones and large bowel cancer. PMID- 1519569 TI - Prediction of Helicobacter pylori in gastric specimens by inflammatory and morphological histological evaluation. AB - Statistical correlations and predictive values were calculated for 330 gastrointestinal biopsies and tissues, of which 248 were from the stomach from 115 patients in this retrospective study, which graded 10 inflammatory and 14 morphological mucosal and submucosal abnormalities and compared them with the presence of Helicobacter pylori. Analysis revealed that 78 (31.5%) of the 248 stomach biopsies and tissues showed H. pylori, and 21 (8.5%) had non-Helicobacter like bacteria, such as rods and cocci. Inflammatory components had high correlations, with specimens containing polymorphonuclear leukocytes (PMNs) showing high specificities and predictive values for a positive test, whereas the chronic inflammatory components had high sensitivities and predictive values for a negative test. Positive morphological correlations existed for mucus depletion, degeneration, regeneration, and ulceration, but intestinal metaplasia and adenocarcinoma had negative correlations. The antrum was most commonly infected, suggesting that intact healthy antral morphology and the neutral mucin in the surface epithelial cells represents the optimal environment for infection. Also, 8.5% of the gastric biopsies and tissues showed non-Helicobacter bacteria associated with inflammation, thus raising the question of colonization versus pathogenesis. PMID- 1519571 TI - Evaluation of duodenal papillary function by ERCP-CT and comparison with endoscopic measurement of pressure in the papillary sphincter zone. AB - Imaging of the main pancreatic duct on ERCP-CT (computerized tomography performed immediately after endoscopic retrograde cholangiopancreatography) was evaluated in 192 patients. Favorable images were obtained in elderly patients, as well as in those with main pancreatic duct dilation, chronic pancreatitis, papillary disease, and choledocholithiasis. In addition, we used a microtransducer inserted through a duodenoscope to measure papillary sphincter zone and main pancreatic duct pressure. We then compared the endoscopic results with the images achieved on ERCP-CT. The patients with favorable images showed higher pancreatic and papillary basal pressure and a faster wave cycle than those with poor images. In addition, significant differences in pancreatic duct pressure and basal pressure were seen. Peak papillary pressure showed no consistent correlations with imaging. Patients with favorable images exhibited an increase in the frequency of irregular papillary sphincter zone waves. We conclude from these findings that good images on ERCP-CT reflect a slow flow of pancreatic juice, which is closely associated with papillary stenosis. PMID- 1519570 TI - Ultrasonically guided fine-needle aspiration of liver lesions. AB - The aim of the present study was to determine the diagnostic accuracy of ultrasonically guided fine-needle aspiration for liver lesions detected by ultrasound scan. A total of 142 aspirations were carried out in 129 patients with unifocal or multifocal liver lesions suspected of malignancy. The aspiration was made with a 22-gauge needle, guided by ultrasound. Based on histological, cytological, and clinical findings, final diagnoses were reached in 123 patients, 96 of whom had malignant liver disease and 27 benign liver disease. Among the 96 patients with malignant liver disease, the cytological findings revealed malignancy in 78 patients (81.3%) and suspected malignancy in five patients (5.1%), but failed to demonstrate malignancy in 13 patients (13.3%). Among 27 patients with benign liver disease, all the cytological findings indicated benignancy. The overall sensitivity, specificity, and positive and negative predictive values for cytological findings were 86.5%, 100%, 100%, and 76.9%, respectively. The diagnostic accuracy of ultrasonically guided fine-needle aspiration was 89.4%. In one patient with incipient chronic disseminated intravascular coagulation, a fatal intraperitoneal bleeding complicated the procedure. We conclude that ultrasonically guided FNA for cytologic diagnosis of liver lesions is highly accurate and is only rarely associated with fatal complication. PMID- 1519572 TI - Gastric emptying in childhood inflammatory bowel disease: nutritional and pathologic correlates. AB - To determine the incidence of gastric emptying abnormalities in children with inflammatory bowel disease, we performed dual liquid/solid-emptying studies on 25 children with ulcerative colitis (UC) and on 45 with Crohn's disease (CD) over a 6-yr period. Nutritional parameters were evaluated initially and at the time of repeat study in those with abnormal emptying after a period of nutritional rehabilitation. All UC patients and 30 of 45 with CD (67%) had normal emptying of both liquid and solid components of the meal. Fifteen children with CD had delayed emptying of the solid liquid. Fourteen of these had preceding weight loss and one had no weight gain for 3 months prior to the study. Twelve complained of upper gastrointestinal symptoms (nausea, early satiety, postprandial epigastric pain, and anorexia), and five had evidence of growth retardation. The group averaged 4.8 abnormal nutritional parameters, compared with an average of 2.2 in those with CD and normal gastric emptying. Twelve of the 15 with abnormal emptying had abnormal gastric and/or duodenal biopsies: 10 were treated with sulfasalazine and prednisone, whereas five were taking only sulfasalazine. Studies repeated 6-15 months later after establishment of weight gain by caloric supplementation showed significant improvements in gastric emptying, nutritional status, and disease activity for the group, despite persistence of upper gastrointestinal disease documented in eight patients who underwent reexamination. PMID- 1519573 TI - Reduction of portal pressure by chronic administration of isosorbide dinitrate in patients with cirrhosis: effects on systemic and splanchnic hemodynamics and liver function. AB - We investigated the chronic effects of isosorbide dinitrate on systemic and splanchnic hemodynamics and liver function in 13 patients with liver cirrhosis and portal hypertension. Placebo administration for 4 wk (n = 4) had no significant effects on these parameters. In contrast, oral administration of 40 mg/day of isosorbide dinitrate for 4 wk (n = 9) caused a significant fall in portal pressure (-18%, p less than 0.02), as evaluated by measurements of the hepatic venous pressure gradient with no modification in hepatic blood flow (from 0.72 +/- 0.29 to 0.71 +/- 0.34 L/min, NS), suggesting decreased intrahepatic or collateral vascular resistance. On the other hand, there was no significant correlation between the changes in mean arterial pressure and hepatic venous pressure gradient (r = 0.42). Thus, it seems unlikely that a reduction in portal blood inflow by baroreceptor-mediated reflex splanchnic vasoconstriction contributed to the fall in portal pressure. In addition, this drug had no adverse effects on liver function, as evaluated by measurements of the intrinsic clearance. These results suggest that chronic administration of isosorbide dinitrate could be a potentially useful and associated with cirrhosis. PMID- 1519574 TI - Stomal complications of gastric bypass: incidence and outcome of therapy. AB - Gastric bypass is an effective treatment for morbid obesity. However, it is sometimes complicated by stenosis or ulceration of the gastrojejunal anastomosis. Stomal ulceration and stenosis developed in, respectively, 12.5% and 12% of 191 patients who underwent gastric bypass. Only 3% had both complications simultaneously. The risk of developing either complication was highest in the first 2 months after surgery. Stomal stenosis responded to endoscopic dilation in all instances, and appears to be a safe and effective method of treating this problem following gastric bypass. Stomal ulceration healed with an H2 blocker and sucralfate administration in all but one patient. Postoperative weight loss was similar in patients with or without stomal stenosis or ulceration. We conclude that, although stomal complications occur in about 20% of all patients undergoing gastric bypass, they can almost always be managed by conservative therapy. PMID- 1519575 TI - Relationship between pancreatic exocrine function and histological changes in chronic pancreatitis. AB - To confirm correlation between function and histology of the exocrine pancreas in chronic pancreatitis, we compared exocrine pancreatic function, as estimated by cholecystokinin secretin test (CST), with histological findings in 108 patients. Exocrine pancreatic insufficiency was graded from 0 to 4 according to the number of abnormal CST parameters. Histological findings also were graded from 0 to 4. Results of CST in 108 patients were normal (grade 0) in 52, equivocal (grade 1) in 23, and abnormal (grades 2-4) in 33. Normal histological findings (grade 0) were observed in 54 patients, equivocal (grade 1) in 15, and abnormal (grades 2 4) in 39. We confirmed that there was a significant correlation between histological grading and overall scoring (tau = 0.59, p less than 0.01) or individual parameters (tau = -0.36 for volume, -0.45 for amylase output, and 0.54 for maximal bicarbonate concentration (p less than 0.01) of CST. Sensitivity of CST was 67% in 39 patients with histologically confirmed chronic pancreatitis, specificity was 90% in 69 patients without chronic pancreatitis, based on histological evidence, and efficiency was 81%. In conclusion, we confirmed a highly significant correlation between direct function test (CST) and histology of the exocrine pancreas. PMID- 1519576 TI - Morning versus evening dose: a comparison of three H2-receptor blockers in duodenal ulcer healing. AB - In a prospective, randomized, single-blind, single-center, controlled study, we compared the effectiveness of single doses of cimetidine 800 mg, ranitidine 300 mg, and famotidine-40 mg given either as evening or morning doses for duodenal ulcer healing. One hundred eighty-six male patients with endoscopically confirmed duodenal ulcer were treated for 6 wk, and ulcer healing was endoscopically evaluated. The duodenal ulcer healing rate for each of the three H2-receptor antagonists was always less after morning administration than was achieved with the respective evening regimen: 59% versus 86% for cimetidine, 83% versus 94% for ranitidine, and 93% versus 97% for famotidine, but the difference was statistically significant for cimetidine only. This study confirms the importance of nocturnal therapy for duodenal ulcer healing. The importance is obscured when H2-receptor antagonists with higher potency and long duration of action are used. PMID- 1519577 TI - Multiple strictures of the small intestine after long-term nonsteroidal anti inflammatory drug therapy. AB - A 60-yr-old female patient with rheumatoid arthritis presented with nonsteroidal anti-inflammatory drug (NSAID)-induced ileal ulcers which caused intestinal bleeding and multiple strictures. Results of investigations, including radiological, pathological, and bacteriological examinations, were not consistent with Crohn's disease or intestinal tuberculosis. Rather, the lesion was characteristic of "diaphragm disease" caused by NSAIDs. Discontinuance of NSAIDs in combination with administration of ornoprostil (prostaglandin E1-derivative), sucralfate, and sulfasalazine put an end to the intestinal bleeding. This is a rate case of a patient with multiple strictures of the small intestine caused by NSAIDs. PMID- 1519578 TI - Ringed esophagus: an association with esophagitis. PMID- 1519579 TI - Leukocytoclastic vasculitis, not associated with Henoch-Schonlein purpura, causing recurrent massive painless gastrointestinal hemorrhage. PMID- 1519580 TI - Obstructive jaundice secondary to primary biliary involvement with Hodgkin's disease. AB - A 41-yr-old man presented with jaundice, night sweats, and weight loss. The patient had been on phenytoin for seizure disorder. The drug was discontinued, and a diminution of bilirubin and transaminases occurred over several weeks. Percutaneous liver biopsy revaled cholestasis at the time of maximal hyperbilirubinemia. Recurrent jaundice ensued several weeks later, and an ERCP revealed a common bile duct lesion. Laparotomy revealed Hodgkin's disease involving the common bile duct and periportal node. This cause represents the first report of extrahepatic biliary obstruction from Hodgkin's disease. PMID- 1519581 TI - Urinary ascites in the immediate postpartum period. AB - New onset ascites in the immediate postpartum period is a rare occurrence most often associated with the Budd-Chiari syndrome. We report a patient who developed postpartum ascites secondary to an intraperitoneal bladder perforation. PMID- 1519582 TI - Common bile duct stones: a cause of chronic salmonellosis. AB - A chronic carrier state of Salmonella spp is present in 0.15% of the population, and is believed to be related to the presence of a diseased gallbladder. We present a patient with common bile duct (CBD) stones, whose bile cultures repeatedly indicated Salmonella typhi, despite an adequate course of antibiotic treatment. The carrier state was abolished after removal of the CBD stones 4 months later. The chronic carrier state may be related to biofilm formation on the surface of the CBD stones. The removal of the biliary stones, which are the most likely reservoir for Salmonella spp, may be a crucial step in eradication of the carrier state. PMID- 1519583 TI - Nodular lymphoid hyperplasia of gut in HIV infection. PMID- 1519584 TI - Fatal pulmonary arterial hypertension complicating noncirrhotic portal fibrosis. AB - A 25-yr-old female with noncirrhotic portal fibrosis underwent a lienorenal shunt for variceal bleed. Ten years after shunt surgery, she presented with progressive breathlessness, and severe pulmonary arterial hypertension was detected, to which she subsequently succumbed. Autopsy revealed classical plexogenic pulmonary arteriopathy. PMID- 1519585 TI - Pancreatic TB: diagnosis by needle aspiration. PMID- 1519586 TI - Octreotide in the management of postoperative enterocutaneous fistulas and stress ulcer bleeding. AB - We report two clinical experiences in the treatment of postoperative enterocutaneous fistula and stress ulcer bleeding with octreotide acetate (Sandostatin). In both patients, upper gastrointestinal bleeding occurred 7 days after operation, and the bleeding proved to be stress ulceration, by panendoscopic examination. Enterocutaneous fistulas also were found in both patients. One was high output (750 ml/day), and the other was low output (50 ml/day). Octreotide 50-100 micrograms was given subcutaneously every 8 h. After three doses of octreotide, a significant reduction in fistula output and control of the stress ulcer bleeding were noted. The fistulas closed promptly after nine doses of octreotide, but the first patient's fistula recurred 2 days later, with fluid losses of about 100-200 ml/day. This fistula closed spontaneously 1 month after discharge. Octreotide appears to be useful as an adjunct to the conventional treatment of enterocutaneous fistulas, especially those complicated by stress ulcer bleeding. PMID- 1519587 TI - Gangliocytic paraganglioma of the papilla of Vater with regional lymph node metastasis. AB - We report a case of duodenal gangliocytic paraganglioma (GP) in a 47-yr-old man. The GP arose in the second portion of the duodenum and was shown by histological examination to consist of epithelioid cells, spindle cells, and ganglion-like cells. Although most of the reported cases of GP have been regarded as benign, in the present case we found that a lymph node in the peripancreatic region contained a metastatic tumor. This is believed to be the third documented case of GP showing regional lymph node metastasis. The metastatic tumor consisted of only epithelioid cells, without spindle cells or ganglion-like cells, supporting the hypothesis that only epithelioid cells have malignant potential. PMID- 1519589 TI - Nonsurgical portosystemic shunting: a radiologic breakthrough. PMID- 1519588 TI - Steroids in alcoholic hepatitis: another salvo of data. PMID- 1519590 TI - Chest pain and the esophagus: is it more obvious in the CCU? PMID- 1519591 TI - Training for straining: biofeedback for pelvic floor dyssynergia. PMID- 1519592 TI - Does "mycobacterioascites" exist? PMID- 1519593 TI - Re:Incidental microvesicular steatosis due to valproic acid anticonvulsant therapy. PMID- 1519594 TI - Pharmacokinetic studies of famotidine in patients with liver cirrhosis. PMID- 1519595 TI - Mixed cryoglobulinemia and hepatitis C virus infection. PMID- 1519596 TI - Use of intravenous omeprazole in emergency cases of gastroduodenal hemorrhage. PMID- 1519597 TI - Expression of glycogen phosphorylase activity in minute gastric carcinoma. PMID- 1519598 TI - Bladder dysfunction and irritable bowel syndrome. PMID- 1519599 TI - Acute febrile alcoholic hepatitis treated with corticosteroids. PMID- 1519600 TI - Massive lower gastrointestinal hemorrhage due to ascariasis. PMID- 1519601 TI - Sepsis-associated renal vasoconstriction: potential targets for future therapy. AB - Systemic sepsis is associated with acute deterioration in renal function despite normal or increased cardiac output. The kidney is often structurally normal, but severe renal vasoconstriction underlies a marked decrease in the glomerular filtration rate (GFR). The mechanisms underlying renal vasoconstriction in sepsis include locally and systemically released vasoconstrictors. Novel peptide and lipid-derived mediators that have been implicated in experimental models of sepsis include endothelin (ET)-1, thromboxane A2 (TXA2), leukotrienes (LTs), and, most recently, noncyclooxygenase-derived prostaglandin F2 (PGF2) analogues. Plasma ET-1 levels are elevated in septic patients and following endotoxin administration in experimental animals; antagonism of the endogenous actions of ET-1 is associated with improvement in renal perfusion and function during experimental endotoxemia. Antagonists of the TXA2 receptor and/or TXA2 synthesis in vivo have been associated with selective improvement in renal vascular tone and preservation of GFR during experimental endotoxemia in several mammalian species. Furthermore, antagonism of the TXA2 receptor inhibits the actions of endogenously released free radical-generated PGF compounds. The latter are the most potent renal vasoconstrictors among the family of arachidonic acid derivatives. Sulfidopeptide LTs, in particular LTC4 and LTD4, are also implicated in the renal vasoconstriction that attends sepsis in rats and other experimental animals. LT hepatobiliary elimination is suppressed during sepsis and endogenous LT production is enhanced. Antagonism of LTD4 receptors is associated with amelioration of renal vasoconstriction. Taken together, these novel potential mediators of renal vasoconstriction during sepsis constitute specific molecular targets for future therapeutic interventions. PMID- 1519602 TI - Systemic hemodynamic abnormalities and vasopressor therapy in sepsis and septic shock. AB - Septic shock, a distributive form of shock, is a common and lethal disease characterized by tachycardia, hypotension, normal or elevated cardiac index, and decreased systemic vascular resistance (SVR). For 2 to 4 days after onset of shock, the left ventricular ejection fraction (LVEF) is depressed; with adequate volume replacement, the left ventricle dilates and cardiac output (CO) is maintained or increased. In survivors, these abnormalities reverse to normal within 7 to 10 days. The myocardial depression found in patients with septic shock is not associated with global myocardial ischemia. In our animal model of sepsis, myocardial depression is not associated with impaired myocardial high energy stores, or abnormal myocardial oxygen utilization. However, septic animals have histopathologic evidence of coronary nonocclusive microvascular damage and myocyte injury. The majority of human deaths caused by septic shock are related to the peripheral vascular dysfunction and multiorgan system failure that occurs over time. The pathophysiology of this disease is complex. Clinical and experimental evidence support the notion that myocardial depression, peripheral vascular abnormalities, and multiorgan dysfunction result from the combined effect of exogenous and endogenous mediators (eg, endotoxin, cytokines, and nitric oxide) released during septic shock. Although conventional therapy with fluids, vasopressors, and antibiotics is effective, the disease still has a high mortality rate. Studies investigating the effects of bacterial toxins and potentially harmful host mediators offer the greatest hope in finding new ways to eradicate this highly lethal disease. PMID- 1519603 TI - Endotoxemia, renal hypoperfusion, and fever: interactive risk factors for aminoglycoside and sepsis-associated acute renal failure. AB - Sepsis and aminoglycoside administration remain leading causes of clinical acute renal failure (ARF). In recent years, a number of experimental studies from different laboratories have indicated that specific components of the septic state, most notably fever, endotoxemia, and renal hypoperfusion, can interact to induce synergistic renal damage, acting in concert to produce acute tubular necrosis and ARF. If sepsis-associated ARF has a multifactorial basis, then a number of interventions directed at one or more of its etiologic components could confer protection. In this brief review, evidence to support these pathophysiological and therapeutic considerations are presented. PMID- 1519604 TI - Long-term beneficial effects of angiotensin-converting enzyme inhibition in patients with nephrotic proteinuria. AB - Angiotensin-converting enzyme inhibitors (ACEI) can reduce proteinuria in diabetic and nondiabetic nephropathy. However, no studies have determined whether this antiproteinuric effect modifies the progression of renal insufficiency. We studied the evolution of 46 nondiabetic patients with nephrotic proteinuria treated with captopril for a minimum of 12 months. The follow-up period before captopril treatment was 12 to 18 months. At the end of follow-up, after captopril introduction (24.4 +/- 7.6 months), proteinuria had decreased from 6.3 +/- 2.5 to 3.9 +/- 3.1 g/24 h (P less than 0.001), with a mean decrease of 45% +/- 28%. The proteinuria decrease was higher in patients with reflux nephropathy, proteinuria associated with reduction of renal mass, inactive crescentic glomerulonephritis, nephroangiosclerosis, and IgA nephropathy, whereas patients with membranous glomerulonephritis and idiopathic focal glomerulosclerosis showed a poorer response. Patients were separated according to a proteinuria reduction greater (group A, 23 patients) or lower (group B, 23 patients) than 45% of the initial value. At the end of follow-up, renal function had not significantly changed in group A with respect to values at the start of treatment: serum creatinine (SCr) was 229 +/- 167 mumol/L (2.6 +/- 1.9 mg/dL) versus 203 +/- 97 mumol/L (2.3 +/- 1.1 mg/dL), and creatinine clearance (CrCl) was 0.80 +/- 0.52 mL/s (48 +/- 31 mL/min) versus 0.87 +/- 0.47 mL/s (52 +/- 28 mL/min). The slope of the reciprocal of Scr (1/SCr) showed a significantly beneficial change after captopril introduction.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1519605 TI - Assessment of iron status by erythrocyte ferritin in uremic patients with or without recombinant human erythropoietin therapy. AB - Erythrocyte ferritin may be a better estimator of iron bioavailability than the conventional markers of iron stores (serum ferritin and transferrin saturation). To investigate the accuracy of these conventional markers in uremic patients compared with erythrocyte ferritin, we studied 29 chronic hemodialysis patients on erythropoietin (EPO) therapy, 18 without EPO therapy, and 22 healthy control subjects. Apart from the red blood cell indices, serum ferritin, transferrin saturation, and erythrocyte ferritin, the analytical study included red blood cell protoporphyrin and plasma aluminum levels. The control group showed erythrocyte ferritin concentrations between 8.3 and 12.5 attograms/cell (95% confidence interval). In the EPO group, red blood cell protoporphyrin correlated negatively with erythrocyte ferritin, but not with serum ferritin or transferrin saturation. In the non-EPO group, serum ferritin, erythrocyte ferritin, and transferrin saturation did not correlate with red blood cell protoporphyrin. Even though erythrocyte ferritin correlated well with serum ferritin in the EPO group (r = 0.61, P = 0.0003), the sensitivity of normal serum ferritin levels (30 to 300 ng/mL) to discard a low erythrocyte ferritin concentration (erythrocyte ferritin less than 7 ag/cell) was 0.53, while the sensitivity of serum ferritin at levels less than 30 ng/mL to indicate an absolute iron deficiency expressed as a low erythrocyte ferritin concentration was 0.28. Only values of serum ferritin and transferrin saturation greater than 300 ng/mL and 35%, respectively, could rule out a relative iron deficiency expressed as a low erythrocyte ferritin and high red blood cell protoporphyrin concentration. Plasma aluminum levels did not correlate with red blood cell protoporphyrin or erythrocyte ferritin levels in either uremic group.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1519606 TI - The occurrence of IgA-nephropathy in patients with diabetes mellitus may not be coincidental: a report of five cases. AB - We describe five patients with IgA-nephropathy complicating diabetes mellitus. In four cases, diabetic glomerulosclerosis was present at the same time. One patient suffered from dermatitis herpetiformis. The observation of the present five cases together with the notion of an increased prevalence in diabetes mellitus of celiac disease and dermatitis herpetiformis suggests that the occurrence of IgA nephropathy in diabetic patients is not mere coincidence. PMID- 1519607 TI - A prospective randomized trial of plasma exchange as additive therapy in idiopathic crescentic glomerulonephritis. The Canadian Apheresis Study Group. AB - Sixty-three patients with crescentic glomerulonephritis (cellular crescents in greater than 50% of glomeruli) were considered for a prospective randomized trial comparing intravenous methylprednisolone, prednisone, and azathioprine with and without plasma exchange. Of 32 patients who fulfilled the inclusion criteria for this study, 16 were randomly assigned to receive drug therapy (control) and 16 to receive plasma exchange as well. The randomization was stratified for initial need of dialysis, and the presence of oliguria and sclerosis. Renal pathology was similar in the two groups of patients. There was no significant difference in the number of patients initially on dialysis who were able to discontinue it during the study (2/7 control v 3/4 plasma exchange), whereas no control but two plasma exchange-treated patients started dialysis during the study. Serum creatinine at randomization was similar in the two groups: 769 +/- 486 mumol/L (8.7 +/- 5.5 mg/dL) in the control group versus 643 +/- 275 mumol/L (7.3 +/- 3.1 mg/dL) in the plasma exchange group. There was no significant difference between the two groups in mean serum creatinine, change in serum creatinine, change in reciprocal, or change in logarithm of serum creatinine at 1, 3, 6, or 12 months following randomization. Power calculation, assuming a 20% difference would be clinically relevant, was 0.94 at 12 months. There was significant morbidity in both groups; there were two deaths within 1 year of randomization, both of pulmonary infection and both in the plasma exchange group. We conclude that plasma exchange offers no additional therapeutic benefit to patients with idiopathic rapidly progressive glomerulonephritis (RPGN) who are not dialysis-dependent at presentation. PMID- 1519608 TI - Intensive plasma exchange in crescentic glomerulonephritis: help or no help? PMID- 1519609 TI - Extreme gestational starvation ketoacidosis: case report and review of pathophysiology. AB - A case of severe starvation ketoacidosis developing during pregnancy is presented. The insulinopenic/insulin-resistant state found during fasting in late gestation predisposes to ketosis. Superimposition of stress hormones, which further augment lipolysis, exacerbates the degree of ketoacidosis. In our patient, gestational diabetes, twin pregnancies, preterm labor, and occult infection were factors that contributed to severe starvation ketoacidosis. Diagnosis was delayed because starvation ketosis is not generally considered to be a cause of severe acidosis, and because the anion gap was not elevated. Improved understanding of the complex fuel metabolism during pregnancy should aid in prevention, early recognition, and appropriate therapy of this condition. PMID- 1519610 TI - Acute renal failure following binge drinking and nonsteroidal antiinflammatory drugs. AB - Two college students who developed reversible acute deterioration in renal function following binge drinking of beer and the use of nonsteroidal antiinflammatory drugs (NSAIDs) are reported. Both patients presented with back and flank pain with muscle tenderness, but showed no evidence of overt rhabdomyolysis. The first case had marked renal failure, with a peak serum creatinine reaching 575 mumol/L (6.5 mg/dL), and acute tubular necrosis was documented by renal biopsy. The second case had only modest elevation in serum creatinine, and renal function rapidly improved on rehydration. The contribution of the potential muscle damage associated with alcohol ingestion to the changes in renal function in these two cases is not clear. However, the major mechanism for the acute renal failure was thought to be related to inhibition of renal prostaglandin synthesis in the face of compromised renal hemodynamics secondary to alcohol-induced volume depletion. PMID- 1519611 TI - Acute unilateral renal failure and contralateral ureteral obstruction. AB - After obstetrical surgery, a young woman developed an acute renal failure of one kidney, the other having been protected by a fortuitous ureteral ligation. The possible effects of a temporary kidney exclusion on itself and on the other kidney are discussed. PMID- 1519612 TI - Bilateral xanthogranulomatous pyelonephritis involving native kidneys in a renal transplant recipient: association with renal cell carcinoma and amyloidosis. AB - An unusual case of a 44-year-old male renal transplant recipient who developed bilateral xanthogranulomatous pyelonephritis (XPN) of his native kidneys is presented. Bilateral nephrectomy specimens showed classic features of XPN. In addition, there was amyloidosis involving both kidneys and a small renal cell carcinoma in the left kidney. To the best of our knowledge, such a combination of pathologic conditions in one patient has not been previously reported. PMID- 1519613 TI - Recertification in nephrology. Nephrology Board of the American Board of Internal Medicine. PMID- 1519614 TI - Occupational exposures and cancer of the colon and rectum. AB - The associations between occupational risks and colorectal cancer were examined in a Swedish population-based, case-referent study. The study was performed in Stockholm in 1986-1988 and included 569 cases and 512 referents. Relative risks (RRs) with 95% confidence intervals were calculated for different occupations/chemicals. Elevated risks of colon cancer were found among male petrol station/automobile repair workers (RR = 2.3, 0.8-6.6) and among males exposed to asbestos (RR = 1.8, 0.9-3.6), while elevated risks of rectal cancer were found among males exposed to soot (RR = 2.2, 1.1-4.3), asbestos (RR = 2.2, 1.0-4.7), cutting fluids/oils (RR = 2.1, 1.1-4.0), and combustion gases from coal/coke/wood (RR = 1.9, 1.0-3.7). However, due to a high correlation between the above-mentioned variables and the few exposed subjects, it is difficult to separate their effects properly. These analyses were adjusted for age. Further adjustments for diet, body mass, and physical activity had little or no influence on the results. PMID- 1519615 TI - Malignant lymphoproliferative diseases in occupations with potential exposure to phenoxyacetic acids or dioxins: a register-based study. AB - The Swedish Cancer Environment Register (CER) is a linkage of census data (e.g., on occupations) with the Swedish Cancer Register. It has been used in different studies to generate hypotheses on occupational risk factors for malignant tumors. In this study the risk for malignant lymphoma and multiple myeloma in occupations with potential exposure to phenoxyacetic acids or other related substances were investigated. An increased standardized incidence ratio (SIR) of 1.3 for multiple myeloma was verified in farmers (no. of cases = 335). This finding applied to both sexes, and the SIR increased over successive time periods. Regarding malignant lymphoma an increased SIR of 1.2 was found in farmers (no. = 227) for the latest time period studied (i.e. 1979-1984). When non-Hodgkin's lymphoma was studied separately, an increased risk (SIR = 1.2) was found only in carpenters (no. = 149), whereas for Hodgkin's disease, sawmill workers (no. = 10) had an increased SIR of 2.1. Physicians also had an elevated risk for malignant lymphoma. A major shortcoming in register studies such as CER is that no individual exposure data on different agents are available. Lack of an association between an occupation and a specific malignant disease, therefore, may not be taken as evidence that persons within that occupation are not at increased risk for that disease. PMID- 1519616 TI - Toluene vapor exposure and urinary excretion of hippuric acid among workers in China. AB - A factory survey was conducted in three provinces in China from 1985 to 1989. The time-weighted average toluene concentrations in breathing zone air were monitored by diffusive sampling, whereas hippuric acid (HA) concentrations in shift-end urine samples were measured by high performance liquid chromatography (HPLC). Exposed workers (456 men and women) were those for whom toluene (up to 548 ppm toluene) accounted for greater than or equal to 90% of total exposure (by vapor concentration in ppm), whereas 517 nonexposed controls were recruited from the same factories or from factories of the same region. There was a linear correlation between the intensity of toluene exposure and HA concentration in the shift-end urine. Comparison of the results with findings in the literature shows that the toluene-induced increase in urinary HA concentration among workers in China is significantly smaller than the published values, whereas HA concentrations in urine samples from nonexposed controls are comparable to the levels previously reported. PMID- 1519618 TI - Evaluation of the utility of a standard history questionnaire in assessing the neurological effects of solvents. AB - Using a standard battery of medical surveillance questions, a study was undertaken to determine if an increase in reported neurologic symptoms was resulting from solvent exposure at a pharmaceutical research, development, and manufacturing site. The prevalence of positive responses to 13 interval history questions pertaining to neurological symptoms was compared between those enrolled in exposed surveillance programs (n = 840) and those enrolled in other, non solvent exposed surveillance programs (n = 1,042). The ratio of positive responders between the exposed and unexposed groups was used to generate a relative prevalence ratio (RPR). No significantly elevated RPRs were seen when the analysis was adjusted for the confounding factors of age, sex, smoking, alcohol use, noise exposure, and number of interval histories. These results suggest that workplace solvent exposures in the employees studied did not appear to result in obvious neurologic symptoms. However, low-level neurotoxic exposures can cause asymptomatic or sub-clinical disorders. Therefore, more sensitive neurotoxic surveillance systems need to be developed. PMID- 1519617 TI - Neurobehavioral effects of long-term occupational exposure to organic solvents: two comparable studies. AB - Two comparable cross-sectional studies were carried out employing the same methodology but involving two separate solvent-exposed populations (N = 90, N = 144). In each study, solvent-exposed workers were compared with age-matched controls on tests selected from the Neurobehavioral Evaluation System and on standardized questionnaire measures of symptomatology and psychiatric state. A similar pattern of results was obtained in the two studies indicating a significant effect on cognitive functioning, after controlling for confounding variables, occurring in those with more than 30 years of exposure. A more specific effect on learning processes was observed in those with more than 10 years of exposure. There were no indications in either study of a solvent-related increase in psychiatric symptoms. PMID- 1519619 TI - Morbidity in retired coke oven plant workers. AB - The effect of past occupational exposure on morbidity was studied in 354 coke oven workers in Lorraine Collieries (France) who retired between 1963 and 1982, and were still alive in 1988; 96% of them participated in this study. Occupational exposure to respiratory hazards during the working life was retraced for each subject. No significant association between the occupational exposure and the frequency of ischemic cardiopathies, arterial hypertension, gastro duodenal ulcers, and respiratory symptoms was revealed. However, subjects who had worked on the Ovens, in the Workshops, and in the Byproducts showed a prevalence of arterial hypertension significantly higher than the non- or slightly exposed subjects. The healthy worker effect phenomenon, the exclusion of deceased subjects, and the small size of this retiree population may conceal possible differences between exposure groups. PMID- 1519620 TI - Morbidity among municipal waste incinerator workers. AB - Incinerator workers are exposed to many toxic compounds, most notably heavy metals. We evaluated medical and exposure monitoring data of an actively employed cohort of Philadelphia incinerator workers following an Agency for Toxic Substances and Disease Registry site survey and National Institute for Occupational Safety and Health (NIOSH) health hazard evaluation (HHE). Of the many airborne samples taken by NIOSH, only four of the personal breathing zone samples were above OSHA or ACGIH standards: one for lead, one for phosphorous, and two for total particulates. Because samples were taken during limited operations (only one of the two incinerators were operating), the results may underestimate historical exposures at this site. We limited our medical analysis to the 86 male workers who participated in the HHE out of the 105 active employees. The 86 employees were divided into potential high and low exposure groups based on a work site analysis done by an independent industrial hygienist. Eight individuals had at least one elevated biological index indicating exposure to a heavy metal. These elevations, however, were unrelated to the workers' exposure categories. Furthermore, no clinically significant mean blood or serum measurements were noted. Thirty-four percent of the workers had evidence of hypertension which increased the risk of significant proteinuria. Neither hypertension nor proteinuria were related to exposure group. Changes in pulmonary function related only to smoking status. Although there was some evidence of an increased risk of exposure to products of incinerator waste, we could not relate the few elevated biological tests to exposure classification. Additional studies are needed to assess the potential health effects of municipal waste incinerator by-products. PMID- 1519621 TI - Responses among New Jersey's largest employers to legislation restricting smoking at the worksite. AB - In 1985, New Jersey enacted a state law requiring that employers with more than 50 employees implement policies to control smoking in places of employment. The 104 largest private employers in New Jersey were surveyed in 1988 to assess their worksite smoking policies. Of the 92 respondents, 97% had implemented restrictive workplace smoking policies. Only 12% of respondents had implemented such policies prior to the date required by the law, and 86% cited the law as the reason for restricting smoking in the workplace. Over two-thirds of respondents placed restrictions on smoking in open areas, while only one-third restricted smoking in private offices. Nonsmoking employees were reported by 80% of respondents to be supportive of restrictive smoking policies, but 23% reported dissatisfaction by their smoking employees. The New Jersey law appears to have been an important factor in the adoption of work place smoking restrictions by the state's largest employers. PMID- 1519622 TI - Microgranulomatous aspergillosis after shoveling wood chips: report of a fatal outcome in a patient with chronic granulomatous disease. AB - Chronic granulomatous disease is characterized by recurrent infections that result from an inability of phagocytes to kill organisms effectively. We describe a patient with this disease who developed aspergillus pneumonia after shoveling moldy cedar wood chips. Despite aggressive therapy, the patient's condition deteriorated and he died. At autopsy, the lungs revealed diffuse granulomas, all of the same age, with aspergillus organisms confined to the granulomas. We propose the term "microgranulomatous aspergillosis" for this response, which does not conform to the commonly described aspergillus syndromes. We conclude that susceptible immunosuppressed patients should be advised to avoid occupational situations where high spore concentrations are generated. PMID- 1519623 TI - Victoria M. Trasko: champion of state-based surveillance of occupational diseases in the United States, 1937 to 1971. AB - Victoria M. Trasko (1907-1979), a relatively unknown figure to many currently practicing occupational health specialists, was a pioneer in state-based surveillance of occupational diseases in the United States. To highlight her accomplishments during her career with the United States Public Health Service from 1937 to 1971, this report briefly reviews her publications on occupational disease surveillance. Her span of work includes guidelines for state industrial hygiene programs, numbers of workers in state occupational health programs, compilation of state and local laws related to industrial hygiene, proposals for standardized reporting of occupational disease, and analysis of trends in workers' compensation and mortality statistics for occupational diseases. She pilot tested the first state-based model system for occupational disease reporting in the United States. She documented the great difficulty experienced by states in getting physicians to report cases of occupational diseases, and pointed out that surveillance of other existing data sources was worthwhile, at least for some occupational diseases. She was the first to report on the distribution of silicosis cases in the United States by state, industry, and job title. She was the first to comment on mortality trends for the pneumoconioses and to document problems in comparability between different International Classification of Disease (ICD) periods. PMID- 1519624 TI - Re: "Changing attitudes and opinions regarding asbestos and cancer 1934-1965". PMID- 1519625 TI - Prevention delayed is prevention denied. PMID- 1519626 TI - How are we going to change our attitudes and opinions regarding asbestos and cancer in the next 20 years? PMID- 1519627 TI - Re: "Changing opinions and attitudes regarding asbestos and cancer 1934-1965". PMID- 1519628 TI - Asbestos and cancer: an early warning to the British TUC. PMID- 1519629 TI - Asbestos and cancer 1934-1965: and what happened thereafter? PMID- 1519630 TI - Public health and epistemology. PMID- 1519631 TI - Re: "Changing attitudes and opinions: asbestos and cancer 1934-1965". PMID- 1519632 TI - The evolution of antihypertensive therapy: current theoretical conditions and individualized treatment options. PMID- 1519633 TI - Hypertensive nephropathy: is a more physiologic approach to blood pressure control an important concern for the preservation of renal function? AB - During the past 2 decades, there have been important reductions in stroke-related morbidity and mortality due to better control of hypertension. However, there has been a lesser effect on the reduction of coronary mortality and far less of an impact on all other forms of noncardiovascular disorders such as renal disease. This suggests that our ability to prevent hypertensive nephrosclerosis through traditional methods of lowering blood pressure may not be as effective as was once thought, particularly in high-risk patients such as blacks, diabetics, the elderly, and patients with preexisting renal disease. One reason that may partially explain the difficulty in protecting the renal circulation from hypertensive damage is the interaction between antihypertensive medications and the aged-related decline in renal perfusion. Depending on their mechanism of action, antihypertensive agents may impair renal blood flow (through plasma volume contraction or reduction) and further aggravate the age-related decline in renal perfusion. A worsening of renal perfusion may activate counterregulatory neurohormonal mechanisms, such as the renin-angiotensin-aldosterone system, which in turn may place the patient at increased risk for the development of glomerulosclerosis through promotion of vascular or mesangial hypertrophic changes or increased intraglomerular pressure, despite an associated reduction in systemic blood pressure. Since antihypertensive agents have such varied effects on systemic and renal hemodynamics, an understanding of the antihypertensive actions in a given patient may have significant influence on renal function. Thus, an improved understanding about the effects of aging and hypertension on the renal microcirculation will hopefully facilitate a more physiologically appropriate antihypertensive medication selection with the expectation that renal function will be benefitted over the long term. PMID- 1519634 TI - Selecting optimum antihypertensive therapy: indications for choosing a calcium channel blocker. AB - In choosing the optimum antihypertensive agent for an individual patient, various factors should be considered. Demographic characteristics (e.g., age, gender, race) and the circadian pattern of blood pressure elevation may influence the response to therapy. Concomitant therapy for coexisting medical disorders must be evaluated for possible drug interactions. Calcium channel blockers, which can be used in any age group, may be particularly useful in hypertensive patients with certain concurrent conditions (e.g., coronary artery disease, migraine, or gastrointestinal motility disorders). Life-style, including occupation and leisure-time activities, may contraindicate the use of certain drugs in a particular patient. It also may be necessary to consider the economic status of the patient, particularly in the elderly, who often have limited disposable income. Since to a great extent successful therapeutic management of hypertension depends on patient compliance, reduced frequency of dosing (i.e., once or twice daily) is desirable. The clustering of morbid events in the hours immediately following awakening highlights the need for therapy that provides 24-hour control, thereby ensuring adequate pharmacodynamic effects during that crucial period. The challenge is to select the most appropriate first-line agent (diuretic, beta blocker, calcium channel blocker, or angiotensin-converting enzyme inhibitor) for a particular patient. PMID- 1519635 TI - Evolution of the treatment of hypertension: what really matters in the 1990s? AB - Over the past decade we have seen a shift in the strategy for the treatment of hypertension, from stepped therapy--involving a highly structured, unvarying series of steps--to recommendations for more individualized treatment. How shall we accomplish that goal? Severe hypertension provides a clear indication to bypass earlier recommendations. Demographic data such as age, gender, and race, often cited, have proved less helpful. Concomitant medical problems, which are found in greater than 50% of hypertensive patients, are most often the crucial determinants in the selection of antihypertensive therapy. Concurrent coronary artery disease, diabetes mellitus, heart failure, azotemia, asthma, chronic obstructive pulmonary disease, borderline cognitive dysfunction, anxiety, and depression are all common. Each has implications for antihypertensive therapy. Moreover, blood pressure reduction is a surrogate for our real goal, which is reduction of cardiovascular risk. Thus, consideration of concomitant medical problems has extended to left ventricular hypertrophy, obesity, hyperlipidemia, and insulin resistance as additional risk factors in hypertension. Consideration of all of these factors makes it possible to individualize antihypertensive therapy in most patients. PMID- 1519636 TI - Novel drug-delivery systems for hypertension. AB - Although novel controlled-release drug-delivery systems have been used in other areas of medicine, their application in the treatment of hypertension has been relatively recent. Biotechnical use of chemical-dispensing systems has been applied to propranolol, clonidine (the transdermal therapeutic system), nifedipine (the gastrointestinal therapeutic system), verapamil (the sodium alginate and spheroidal oral-delivery absorption system), felodipine (the hydrophilic gel principle), metoprolol succinate (the multiple-unit pellet system), and diltiazem (one system comprising sustained-release beads and the other utilizing the patented Geomatrix extended-release system). Oral drug delivery systems allow antihypertensive agents that previously had to be administered two to four times daily to be administered once each day. Potential disadvantages of the oral controlled-release products include delayed attainment of pharmacodynamic effect, unpredictable or reduced bioavailability, enhanced first-pass hepatic metabolism, dose dumping, sustained toxicity, dosing inflexibility, and increased cost. Potential advantages include reduced dosing frequency, enhanced compliance and convenience, reduced toxicity, stable drug levels, uniform drug effect, and decreased total dose. Although skin reactions are common, the transdermal drug delivery of clonidine provides another innovative approach to supplying transcutaneous, controlled, continuous delivery of drug for 7 days. It is possible that future research will prove that the agents that provide complete 24-hour control may reduce the cardiovascular events associated with the early-morning blood pressure surge. This evolution in antihypertensive therapy to achieve once-daily dosing may prove to be of great value to both physicians and patients in the 1990s. PMID- 1519637 TI - Clinical experience with a once-daily, extended-release formulation of diltiazem in the treatment of hypertension. AB - Although calcium channel blockers were only recently approved for antihypertensive therapy, 10 years of data have demonstrated their beneficial effects. Among the available calcium channel blockers, diltiazem hydrochloride appears to have a highly favorable side-effect profile. A new, extended-release formulation of diltiazem has been developed for the treatment of essential hypertension. The safety and efficacy of various once-daily doses of this new formulation were assessed in two multicenter studies. The first study was a dose ranging trial of 275 patients with mild-to-moderate hypertension. Patients were randomly assigned to once-daily diltiazem (120, 240, 360, or 480 mg) or placebo for a 4-week, double-blind treatment period. A patient subgroup underwent ambulatory blood pressure monitoring (ABPM) twice. Once-daily diltiazem (dose range, 240-480 mg) significantly lowered trough systolic and diastolic blood pressure in a clearly dose-related fashion. ABPM results demonstrated consistent decreases in systolic and diastolic blood pressure throughout the 24-hour dosing interval. Dosages greater than or equal to 240 mg/day provided trough drug blood levels within the therapeutic range (i.e., greater than or equal to 40 ng/mL). The second study was a forced-escalation trail of 115 patients with mild-to moderate hypertension. Patients were randomized to treatment with either placebo or escalating dosages of diltiazem (180 mg/day for 2 weeks, 360 mg/day for 2 weeks, and then 540 mg/day for 2 weeks). Statistically significant (p less than 0.01) reductions in supine systolic and diastolic blood pressure were observed with the 360 mg/day and 540 mg/day dosages. Dose escalations resulted in incremental blood pressure reductions and an increase in the percentage of responders. There was a significant correlation between diltiazem peak and trough plasma concentrations and antihypertensive effects in both studies, supporting the 24-hour efficacy of this extended-release formulation. Diltiazem administered once daily was found to be safe and well tolerated by the patients in these studies; adverse events were generally mild, with an incidence similar to placebo. Results indicate that this new extended-release formulation of diltiazem, administered once daily in doses greater than 120 mg, effectively lowers systolic and diastolic blood pressure in patients with mild-to-moderate essential hypertension. PMID- 1519638 TI - Marked parental consanguinity as a cause for increased major malformations in an Israeli Arab community. AB - It is common among Israeli Arabs who live in the villages to prefer consanguineous marriages, particularly among first cousins. In addition, such villages are populated by a few (less than 20) original families, and inter family/inter-village marriages are infrequent. The purpose of this study was to examine the consequences of such "consanguinity" in Taibe, a large Arab village, 30 km from Tel Aviv. Six hundred ten families were prospectively ascertained through infants who were routinely seen in the local "Well Baby Clinics." A significant increase in the incidence of major malformations was noted in relation to the closeness of the parental relationship. For the index cases group the prevalence of individuals with major malformations were 5.8% in the product of inter-village marriages, 8.3% in the intra-village non-related matings, 15.1% in the distant consanguineous group, and up to 15.8% in the progeny of first cousin marriages (P less than 0.001). In the siblings of these index cases, the frequency of major malformations was 4.3%, 4.5%, 10.5%, and 10.3%, respectively. Analysis of the major malformations by each body system showed the same trend. The study demonstrates a marked high rate of consanguineous marriages, whose effect leads to a marked increase in major malformations and thus a prominent public health problem in such villages. This requires a unique genetic counseling approach. PMID- 1519640 TI - Ullrich-Turner syndrome with unilateral agenesis of breast, nipple, and pectoralis major. AB - A 16-year-old girl with mosaic Ullrich-Turner syndrome [45,X/46,X,i(Xq)] had agenesis of the left breast, nipple, pectoralis major, and agenesis of hair follicles of the left axilla. This appears to be the first description of this anomaly in the Ullrich-Turner syndrome. PMID- 1519639 TI - Reproductive decision making of aunts and uncles of a child with cystic fibrosis: genetic risk perception and attitudes toward carrier identification and prenatal diagnosis. AB - This paper evaluates the perceived genetic risk, the perceived burden, the impact on reproductive decision making, and the attitudes of aunts and uncles of a child with cystic fibrosis toward carrier identification, prenatal diagnosis, and pregnancy termination. A mailed questionnaire was sent to the aunts and uncles of 32 CF children (1) who attended the Paediatric Department of the University Hospital and (2) whose parents agreed to give the names and addresses of their sibs. The results for the 109 respondents aged less than 40 years are discussed. About one-fourth of them was aware of the "approximate" level of the risk to be a carrier of the CF gene and/or of the risk of having a CF child themselves. Nevertheless the subjective evaluation of the genetic risk has played a part in the reproductive decision-making process of at least 39% of the respondents. About three-fourths would (probably) make use of heterozygote detection and would (probably) ask for prenatal diagnosis should they become pregnant. It is striking that less than half of the group would interrupt the pregnancy should the fetus be affected. The intention to use prenatal diagnosis was significantly correlated with age and educational level while the acceptance of pregnancy interruption was significantly correlated with perceived burden, respondents' age, and health situation of the proband. PMID- 1519641 TI - Survey of mentally retarded males for cutis verticis gyrata and chromosomal fragile sites. PMID- 1519642 TI - Confirmation of assignment of a locus for Rubinstein-Taybi syndrome gene to 16p13.3. AB - A two month-old girl was diagnosed as a case of Rubinstein-Taybi syndrome (RTS) on typical facial dysmorphism, broad and duplicated distal phalanges of thumbs and halluces, growth retardation and psychomotor development delay. Chromosome analysis demonstrated a de novo pericentric inversion of one chromosome 16: 46,XX,inv(16)(p13.3;q13). This association confirms assignment of a locus for RTS gene to 16p13.3, as two others translocations involving the same breakpoint have already been reported. PMID- 1519643 TI - Multisystem obstruction with cholestasis, pigmentary retinopathy, and cleft palate: a new syndrome? AB - A number of systemic abnormalities associated with cholestasis have been reported in the literature. This paper describes two unrelated patients with cholestasis and an unusual constellation of abnormalities including cleft palate/lip, hydronephrosis/hydroureter, retinal pigmentation, and intestinal septum. PMID- 1519644 TI - 7p deletion syndrome: an adult with mild manifestations. AB - Deletion of 7p results in a wide spectrum of congenital abnormalities and minor facial and hand anomalies, often including craniosynostosis. We report on the oldest recognized patient with this disorder, a 24-year-old woman with an interstitial deletion from p15.3-p21.2 or p21.3. The manifestations in this patient are milder than those of previously described patients, and include borderline mental retardation, short stature, minor facial anomalies, and several skeletal changes. The absence of craniosynostosis in this patient is noteworthy, given previous suggestions that there is a specific locus for this finding in the 7p region. Twelve cases of 7p deletion, in which the missing segment overlaps that of the current case, are reviewed. This case delineates a broader spectrum for patients with 7p deletion syndrome. PMID- 1519645 TI - Unbalanced translocation 46,XY,-15,+der(22)t(15;22)(q13;q11)pat: case report and review of the literature. AB - We present a boy with a rare unbalanced translocation 46,XY, 15,+der(22),t(15;22)(q13;q11) pat. Previous reports of similar chromosome findings mention only the Prader-Willi phenotype. At birth, his manifestations included severe hypotonia and lethargy, (typical of deletion of 15pter----q13); hypertelorism, down-slanting small palpebral fissures, preauricular tags, long philtrum (typical of duplication of 22pter----q11); severe laryngotracheomalacia, and proximal implantation of the thumb. In a review of the literature on chromosome abnormalities involving duplication of 22q11 the associated clinical phenotype consists of mild mental retardation, microcephaly, hypotonia, hypertelorism, down-slanting palpebral fissures, a long philtrum, cleft or highly arched palate, and ear abnormalities. Preauricular pits or tags are common. Cardiovascular defects, renal and genital problems and dislocated hips are frequently present. Anal atresia and colobomata are mainly seen in cat-eye syndrome, the phenotype associated with idic 22q11. Our findings indicate that patients with unbalanced t(15;22) can have manifestations of the dup 22q11, in addition to the previously reported Prader-Willi phenotype, even if the duplicated segment is small. PMID- 1519646 TI - Unusual short rib-polydactyly syndrome. AB - We present a case of lethal short rib-polydactyly syndrome (SRPS) that cannot be categorized into the existing classification. A nosologic discussion is presented. To our knowledge, situs inversus totalis, as in our case, has not been described before in any SRPS. PMID- 1519647 TI - Complementary duplication and deletion of 17 (pcen----p11.2): a family with a supernumerary chromosome comprised of an interstitially deleted segment. AB - A sister and brother were investigated because both were developmentally delayed although they had somewhat different physical anomalies. The girl was found to have an interstitial deletion of chromosome 17. Her karyotype was 46,XX,del(17) (pter----p11.2::cen----qter). Her brother had normal chromosomes in peripheral lymphocytes. Cytogenetic investigation of the mother showed the presence of the same deletion as in her daughter and a small supernumerary chromosome. The supernumerary chromosome appeared to contain the material deleted from the short arm of 17 since the mother's phenotype was normal. Study of skin fibroblasts in her son showed that he was mosaic for a normal cell line and one that contained the extra small chromosome; thus, he had mosaic partial trisomy 17(cen----p11.2). The origin of the centromere and telomere(s) of the small supernumerary chromosome in this family presents an interesting problem. PMID- 1519648 TI - Early neurological manifestations and brain anomalies in Marden-Walker syndrome. AB - We report on an infant with the Marden-Walker syndrome. In addition to the consistent neurological abnormalities described previously in this syndrome, the infant had a striking neurological constellation, absence of primitive reflexes, jerky eye movements, failure to habituate to repeated stimuli, inadequate behavior development, and absence of orientation responses to visual or auditory stimuli. Muscle biopsy showed a similar pattern to the congenital fiber-type disproportion. Ultrasonograms and magnetic resonance imaging of his brain demonstrated absence of corpus callosum, colpocephaly, hypoplastic brainstem, hypoplasia of the inferior vermis and of the cerebellar hemispheres. These findings further delineate this syndrome and suggest that prenatal central nervous system (CNS) dysfunction, mainly of the cerebellum and brainstem, may play a significant role in the pathogenesis of the Marden-Walker syndrome. PMID- 1519649 TI - Familial intestinal malrotation with midgut volvulus and facial anomalies: a disorder involving a gene controlling the normal gut rotation? AB - We report on 2 sisters with congenital midgut volvulus. Both had similar facial changes different from those of their parents and the other 2 unaffected sibs. Both parents had normal barium meal roentgenograms. The occurrence of these abnormalities in sibs born to parents with apparently normal gastrointestinal tract anatomy suggest autosomal recessive inheritance, although a coincidence, multifactorial or autosomal dominant inheritance with nonpenetrance in either of the parents cannot be excluded. PMID- 1519650 TI - Glaucoma-lens ectopia-microspherophakia-stiffness-shortness (GEMSS) syndrome: a dominant disease with manifestations of Weill-Marchesani syndromes. AB - We report on a syndrome of progressive joint stiffness, glaucoma, and lens dislocation observed in three generations and compare it with two previous records of short stature, lens ectopia, and articular limitation. This family confirms the existence of a dominant Weill-Marchesani-like syndrome. We suggest that it could be related to the Moore-Federman syndrome. We coin the acronym GEMSS syndrome (Glaucoma, Ectopia, Microspherophakia, Stiff joints, Short stature) to distinguish this dominant Weill-Marchesani-like syndrome from the classic, recessively inherited syndrome. PMID- 1519651 TI - Hawkinsinuria in two families. AB - Hawkinsinuria, a disorder of tyrosine metabolism has been documented in two families in the United States, in one of which there was clear evidence of autosomal dominant inheritance. Metabolic acidosis and failure to thrive appear to be confined to infancy. Tyrosyl metabolites and 5-oxoproline are also found only in infancy, while 4-hydroxycyclohexylacetic acid was present only with time. The disease may be detected by organic acid analysis or by staining an electropherogram for sulfur containing compounds. PMID- 1519652 TI - Congenital anomalies concomitant with persistent primary congenital hypothyroidism. AB - The Israeli national neonatal screening program for congenital hypothyroidism (CH) was initiated in May 1978. The overall incidence of persistent primary congenital hypothyroidism (PPCH) during the first 10 years of screening was 1:2,950 live births. The purpose of this study was to ascertain the incidence of congenital extrathyroid anomalies (ETAs) among the infants with PPCH and to compare it with the Israeli Birth Defect Monitoring System data. Among 243 PPCH infants on whom adequate data were available, 38 infants (15.6%) had associated congenital anomalies. Fourteen infants had congenital cardiac anomalies (5.8%): VSD (n = 7), PDA (n = 3), PS (n = 2), one mitral insufficiency, and one congenital atrial flutter. Eight children (3.3%) had congenital dislocation of the hip; their M:F ratio was 3:5 similar to the M:F ratio in CH (unlike the ratio in the general population). Some additional anomalies were considerably more common than in the general population. It is reasonable to assume that teratogenic effects active during organogenesis may affect simultaneously many organs, including the developing thyroid, causing a relatively high percentage of CH infants with congenital ETA. PMID- 1519653 TI - Xp22.3 microdeletion syndrome with microphthalmia, sclerocornea, linear skin defects, and congenital heart defects. AB - We report on an infant girl with congenital erythematous, linear skin lesions on face and neck, bilateral microphthalmia, sclerocornea, cataracts, and a complex cardiac anomaly including atrial septal and ventricular septal defects. This patient had an Xp22.3 microdeletion and a chromosome satellite on the abnormal X p-arm. The abnormal X chromosome was late replicating in peripheral blood lymphocytes and cultured skin fibroblasts. Four other patients with similar congenital anomalies and Xp deficiency have been reported previously and are compared with this patient. One patient had an interstitial or terminal deletion, but in others the material translocated to Xp22.3 was variable (Yq material in two patients, and Yp material and an unidentifiable satellite in one patient each). Several mechanisms are suggested by which this chromosome abnormality might produce this phenotype in these patients. Our patient is the first with this syndrome to have a congenital heart defect. PMID- 1519654 TI - Anencephaly and limb deficiencies. AB - Limb deficiencies (LDs) are rarely reported in anencephalic infants. A review of 662 patients in the literature on non-neural defects in anencephaly only showed five patients with LDs. We report on eight patients with various LDs from the records of 141 necropsies of the anencephalic infants found among 495,830 births. Compared with another group of anencephalic infants reported in the literature, the patients in this group of anencephalic infants with LDs were predominantly male, their mean gestational age was younger by approximately 5 weeks, their mean birth-weight was approximately 1,400 g less, and they presented with a higher incidence of polyhydramnios during gestational development. The association of this pair of anomalies, which was 100 times more frequent than expected, seems not due to chance. Since all eight patients had other multiple congenital anomalies (MCA), in addition to anencephaly and LDs, the postmortem study should be mandatory in anencephalic infants with LDs. The most common associated anomalies were cardiovascular and renal defects. Oral clefts, diaphragmatic hernia, esophageal atresia, and imperforate anus were also observed in these infants. The recognition of LDs in anencephalic infants indicates severe and extensive disturbance of the early embryogenesis (blastogenesis), which affects the midline of the embryo. PMID- 1519655 TI - Double mosaic aneuploidy: 45,X/47,XY,+8 in a male infant. AB - We report on a 13-month-old boy with abnormalities consistent with mosaic trisomy 8 syndrome and male genitalia with partial penoscrotal transposition without hypospadias, a retractile left testis in inguinal canal, and an absent right testis. A voiding cystourethrogram showed an outpouching close to the lower right side of the bladder (utriculum) and bilateral hydronephrosis secondary to vesicoureteral reflux. Peripheral blood karyotype was 45,X/47,XY,+8. The karyotype of cultured skin fibroblasts was 47,XY,+8 with no 45,X cells detected among 20 cells counted. Tissues removed during surgery documented a 45,X/47,XY,+8 complement in the left testicle and utriculum, but only a 45,X line among 20 cells counted from vas deferens tissue. A possible mechanism for the origin of this previously unreported mosaicism might be an abnormal zygote with a 47,XY,+8 complement with subsequent simultaneous loss of chromosome Y and 8 in a cell at a very early embryonic stage. PMID- 1519656 TI - Congenital contractural arachnodactyly with unilateral lower limb deficiency. PMID- 1519657 TI - Assessment of body composition in the Prader-Willi syndrome using bioelectrical impedance. AB - The accurate assessment of body composition is of importance in the Prader-Willi syndrome. Many techniques are not applicable due to ethical or practical reasons. However, the bioelectrical impedance technique is a rapid, painless, noninvasive method of estimating total body water and hence, fat-free mass in obese children and adolescents. We have compared estimates of total body water derived from bioelectrical impedance with actual measurements taken, using H2 18O dilution, in 14 children with Prader-Willi syndrome. Existing equations for predicting total body water from impedance showed a bias to underestimate actual measures of body water. There were positive correlations between the degree of underestimation with age and body fatness. It is possible that changes in body shapes influence bioelectrical impedance measurements in obese individuals, and that a prediction equation based upon a normal population will not be applicable to obese individuals. PMID- 1519658 TI - Beare-Stevenson cutis gyrata syndrome. AB - Beare-Stevenson cutis gyrata syndrome consists of skin furrows of corrugated appearance, acanthosis nigricans, craniofacial anomalies, particularly craniosynostosis and ear defects, anogenital anomalies, skin tags, and prominent umbilical stump. Four cases of this striking syndrome are reported. Together with two previously reported cases, the syndrome is delineated from the six known cases. Cutis gyrata variably affects the scalp, forehead, face, preauricular area, neck, trunk, hands, and feet. Craniosynostosis is present in four cases, with cloverleaf skull in three of these. Intrauterine growth has been normal in all cases. Performance and life expectation appear to be related to the presence or absence of cloverleaf skull. All cases observed to date have been sporadic. Increased paternal age suggests the possibility of an autosomal dominant mutation. PMID- 1519659 TI - Upper and lower airway compromise in the Apert syndrome. AB - Both upper and lower airway compromise may be responsible for early death in some patients with the Apert syndrome. We report on two and review six cases with complete or partial cartilage sleeve abnormalities of the trachea. Possible mechanisms include tracheal stenosis and/or lack of tracheal distensibility which may result in respiratory inefficiency, inability to clear secretions, and/or increased liability to surface injury from tracheal suctioning. Upper airway compromise, consisting of obstructive sleep apnea and cor pulmonale, may result from reduced nasopharyngeal and oropharyngeal dimensions in the Apert craniofacial configuration. PMID- 1519660 TI - Expression of multi-cytokine resistance and multi-growth factor independence in advanced stage metastatic cancer. Malignant melanoma as a paradigm. AB - Evidence is briefly reviewed, primarily in the context of human melanoma, which suggests that acquisition of resistance to multiple, structurally diverse, growth inhibitory cytokines occurs during malignant tumor progression. A similar pleiotrophy appears to occur with respect to growth factor independence. Also discussed is the notion that growth factors that behave as inhibitors for early stage, benign tumor cells can 'switch' so as to function as mitogens for tumor cells from more advanced stages of disease progression, i.e., when the cells acquire competence for metastasis. The combined phenotypes of 'multicytokine resistance' and 'multi-growth factor independence' help provide tumor cells with the competence to grow in the mesenchymes of the primary organ site and in distant organs. PMID- 1519661 TI - Serum amyloid A gene transcription in synovial cells during retroviral arthritis. AB - In situ hybridization was used to demonstrate serum amyloid A (SAA) gene expression in arthritic joint tissue from lentivirus-infected sheep and goats. SAA gene transcription occurs in isolated individual synovial cells and occasional giant cells but not in uninfected or uninflamed synovial tissue. These findings support the notion (derived from in vitro observations) that at least one member of the SAA gene/protein family may function as an autocrine collagenase inducer in inflammatory arthritis. Since we used heterologous DNA probes derived from human clones, our findings also support the growing evidence for interspecies conservation of SAA genes. PMID- 1519662 TI - In situ hybridization and immunohistochemistry of p53 tumor suppressor gene in human esophageal carcinoma. AB - We have studied expression of p53, a tumor suppressor gene, by using both immunohistochemistry and in situ hybridization in 20 cases of squamous cell carcinoma of the esophagus. Immunohistochemical analysis was performed by using monoclonal antibody pAb1801. Immunoreactive p53 was observed in the nuclei of the tumor cells in 17 cases. We used 35S-labeled anti-sense single-stranded synthetic oligonucleotide probe ON102, which hybridized with DNA sequence near the 5' end of p53, for in situ hybridization. In all the cases of invasive squamous cell carcinoma studied, no significant accumulation of p53 hybridization signals was observed in carcinoma cells. This result indicates that overexpression of p53 observed by immunohistochemical staining is not due to an increase in the steady state level of p53 mRNA in frank carcinoma cells. In six cases of morphologically normal esophageal mucosa distant from carcinoma, accumulation of hybridization signals was observed in basal and parabasal cells of the mucosa. The mucosa of these cases was negative for p53 immunoreactivity except for one case showing sporadic positivity. Accumulation of hybridization signals was observed in foci of squamous dysplasia not associated with invasion in three cases. PMID- 1519663 TI - Relationship between interleukin-1 beta and platelet-activating factor in the pathogenesis of acute immune complex alveolitis in the rat. AB - Intrapulmonary interleukin-1 beta (IL-1 beta) participates in the pathogenesis of acute IgG immune-complex alveolitis through a mechanism involving neutrophil recruitment. We have examined the relationship between intrapulmonary IL-1 beta and locally produced platelet-activating factor (PAF) in the development of acute alveolitis. Instillation of IgG anti-bovine albumin into the lungs of rats, followed immediately by intravenous infusion of bovine serum albumin (BSA), resulted in acute neutrophil-mediated lung injury. Development of IgG immune complex lung injury was accompanied by three- and five-fold increases in bronchoalveolar lavage (BAL) fluid and whole lung PAF levels, respectively. Intratracheal administration of the PAF antagonists, WEB-2086 (Boehringer) or L 652,731 (Merck, Sharpe, and Dohme, Rahway, NJ), reduced pulmonary vascular leakage. Neutralization of intrapulmonary IL-1 activity with anti-IL-1 beta antibodies reduced pulmonary vascular permeability and whole lung PAF levels. Morphometric analysis and whole lung myeloperoxidase measurements revealed a differential effect between the PAF antagonists and anti-IL-1 beta with respect to pulmonary neutrophil recruitment. Intratracheal instillation of anti-IL-1 beta retarded net pulmonary neutrophil recruitment while the PAF antagonists retarded migration of neutrophils from the interstitial/vascular compartments into the alveolar compartment. Intratracheal instillation of anti-IL-1 beta plus L-652,731 resulted in reduction in lung vascular permeability and retarded net pulmonary neutrophil recruitment. No additive effect was observed. Stimulation of isolated mouse alveolar macrophages with recombinant murine IL-1 beta or IL-1 alpha resulted in rapid, dose-dependent, and cell concentration-dependent increases in PAF secretion. These data suggest that intrapulmonary IL-1 beta amplifies local PAF production and that IL-1 beta and PAF modulate different aspects of pulmonary neutrophil recruitment. PMID- 1519664 TI - Influence of genetics on the nephritogenic potential of proteoglycans. AB - Nephritogenic potential of antibodies directed against one of the glomerular basement membrane (GBM) components, i.e., heparan sulfate-proteoglycan (HS-PG), was investigated in different strain of rats, i.e., Brown Norway, Lewis, Long Evans, and Sprague-Dawley. The rats were given two intravenous injections of anti HS-PG antibody on days 1 and 3, and killed 2 to 8 weeks later. Before killing, blood and urine were collected for determination of anti-rabbit IgG levels and excretion of proteins, respectively. In addition, the right kidney was perfused with 125I-anti-rat IgG to quantitate the amount of immune-complexes present within the GBM. The tissues were processed for morphologic, autoradiographic, and immunofluorescent studies. The anti-HS-PG antibody was seen uniformly bound to GBM equally in all strains of rats. However, the protein-uric response was as follows: Brown Norway much much greater than Lewis much greater than Long Evans greater than Sprague Dawley. Also, the glomerular cells, monocytes in the glomerular capillaries, immunoreactivity of rat IgG and C3 frequency of subepithelial immune deposits, serum levels of anti-rabbit IgG, and the amount of 125I-anti-rat IgG bound to the GBM were proportionately increased among different strains of rats. The data suggest that the sustained presence of anti-HS-PG antibodies in the subepithelial aspect of the GBM with differential humoral response in the production of the antibody by the host most likely attributed to the variable glomerular damage in different strains of rats. Thus, it seems that the genetic makeup of a given strain of rat heavily influences the nephritogenic potential of an antibody and consequentially the outcome of the immune complex mediated glomerular injury. PMID- 1519665 TI - Nonradioactive in situ hybridization using digoxigenin-labeled oligonucleotides. Applications to musculoskeletal tissues. AB - We have optimized a technique for in situ localization of specific mRNAs using digoxigenin-11-dUTP-labeled oligonucleotide probes. DNA probes were synthesized for type I and type II collagen as well as transforming growth factor-beta 1 and 2 (TGF beta 1 and TGF beta 2). Control experiments, such as competitive inhibition, nonsense sequence hybridization, and RNAse digestion all indicated that the technique was highly sensitive and specific. In sections of growth plate, type II collagen mRNA was predominantly expressed in the lower proliferative and upper hypertrophic zone, whereas chondrocytes in articular cartilage stained equally. These techniques then were applied to sections cut from archival pathology specimens of musculoskeletal tissues. Primitive chondrocytes in a chondrosarcoma expressed type I and type II collagen mRNA, but did not stain with the nonsense probe. Sections from an osteosarcoma, an aneurysmal bone cyst, and a neurofibroma also were investigated. The ability to use chemically synthesized oligonucleotide probes, the high resolution, and the short development times possible with this in situ procedure makes this technique appealing for applied research into the gene expression of normal and pathologic cellular events. PMID- 1519666 TI - Coexpression of type I and type II human macrophage scavenger receptors in macrophages of various organs and foam cells in atherosclerotic lesions. AB - Macrophage scavenger receptors are trimeric membrane glycoproteins implicated in the pathologic deposition of cholesterol in arterial walls during atherogenesis. Two types of cDNAs for functional human receptors have been cloned, but their physiologic roles remain obscure. To study the expression of these receptors, the authors generated antibodies against scavenger receptor type-specific synthetic peptide. Immunohistochemical examination using these antibodies and other anti human receptor antibodies shows that type I and type II receptor proteins can be detected in foam cells in various stages of atherosclerosis, most evidently in fatty streaks. Co-expression of the two types of receptor protein was also detected in macrophages of various organs. Both types of the protein were detected on the surface and the membrane of endosomes in macrophages. These results indicate that both type I and type II scavenger receptors are expressed and functionally active in physiologic and pathologic conditions. PMID- 1519667 TI - Interaction of human malignant melanoma (ST-ML-12) tumor spheroids with endothelial cell monolayers. Damage to endothelium by oxygen-derived free radicals. AB - Clinical and experimental observations suggest that tumor-induced endothelial cell injury may be one of several initial events in the establishment of tumor metastases. To test this hypothesis, the authors have analyzed the interaction of malignant melanoma (ST-ML-12) multicenter tumor spheroids with endothelial cell monolayers in a three-dimensional coculture system. After 1.5 hours of interaction, the authors observed a toxic effect on endothelial cells in the perispheroid region. The latter was demonstrated by testing membrane integrity with the fluorescent probes acridine orange/ethidium bromide and resulted in sensitivity to shear stress of the damaged cells. The endothelium then underwent a regenerative cycle to replace the denuded halo. Addition of the oxygen radical scavenging enzyme superoxide dismutase to the culture medium prevented this endothelial cell damage in a dose-dependent manner for up to 12 hours. By contrast, catalase, deferoxamine mesylate, allopurinol, and the proteinase inhibitors soybean trypsin inhibitor and aprotinin were not protective under the same conditions. The endothelial damage was dependent on the attachment of the spheroids. Medium conditioned by ST-ML-12-spheroids proved to be ineffective. A similar, but less prominent, deleterious effect was seen when human peritoneal mesothelial cells were used in place of the human umbilical vein endothelial cells. Spheroids of the uroepithelial cell line HU-609 were used as control. No toxicity was observed in these cocultures. Melanin biosynthesis is associated with the production of oxygen-derived free radicals. The results suggest a possible implication of these free radicals in metastasis formation of malignant melanoma. PMID- 1519669 TI - Localization of transforming growth factor-alpha in human appendageal tumors. AB - Transforming growth factor-alpha (TGF alpha) is a potent mitogen for epithelial cells that has been localized to normal human appendageal epithelia. To further understand the role of TGF alpha in human appendages, we examined TGF alpha expression immunohistochemically in 17 types of human appendageal tumors differentiating toward hair follicles, eccrine, apocrine, and sebaceous glands. In order of decreasing degrees of differentiation, tumors could be divided into hyperplasias, adenomas, benign epitheliomas, and primordial epitheliomas. Using an antibody that recognizes primarily the 6-kd and 13-kd forms of TGF alpha, TGF alpha immunostaining in 16 of 17 tumor types analyzed was found to follow a similar pattern, with expression in hyperplasias greater than adenomas greater than benign epitheliomas greater than primordial epitheliomas. Within a given tumor, TGF alpha expression also correlated well with the known differentiation state of the tumor cell types. The results suggest that TGF alpha expression is directly correlated with the differentiation state of hair follicle, eccrine, apocrine, and sebaceous tumors in human skin, and raises the possibility that TGF alpha may play a role in the differentiation of appendageal epithelia. PMID- 1519668 TI - Production of matrix metalloproteinases 2 and 3 (stromelysin) by stromal cells of giant cell tumor of bone. AB - Matrix metalloproteinases play a central role in the catabolism of extracellular matrix macromolecules. Here the authors report that giant cell tumor of bone (GCT) produces two matrix metalloproteinases (MMPs) in zymogen form, which have been identified as proMMP-2 (also known as "72-kDa-progelatinase/type IV procollagenase") and proMMP-3 (prostromelysin). Giant cell tumor is known to consist of two major cell populations, multinucleated giant cells and stromal cells. On several passages of the tumor cells in culture, only stromal cells proliferated. These stromal cells produced proMMP-2 but not proMMP-3. Addition of the conditioned medium of primary GCT culture or human macrophage-conditioned medium to the passaged stromal cells induced the production of proMMP-3. The production of proMMP-3 was also induced by interleukin 1 (IL-1), but not by tumor necrosis factor alpha (TNF alpha). ProMMP-1 (tissue procollagenase) was not detected even after treatment with these stimuli. Immunohistochemical studies have demonstrated that multinucleated giant cells in GCT both produce IL-1 and TNF alpha, suggesting that IL-1 secreted by multinucleated giant cells may be responsible for in vivo production of proMMP-3 by the stromal cells. The authors propose that GCT has a self-stimulatory system for the production of matrix degrading proteinases and that the ability of the passaged stromal cells to synthesize and secrete proMMP-3 with appropriate stimuli may contribute the malignant behavior of GCT. PMID- 1519670 TI - Localization of SIV in the genital tract of chronically infected female rhesus macaques. AB - Despite the fact that human immunodeficiency virus (HIV) is transmitted primarily by sexual contact, the biology of the sexual transmission of HIV is poorly understood. Simian immunodeficiency virus (SIV) can be transmitted to female rhesus macaques by placing cell-free virus into the vaginal canal, and SIV can be isolated from the vaginal secretions of infected rhesus macaques. The authors examined the genital tracts from 16 chronically infected female rhesus macaques and localized SIV-infected cells using in situ hybridization and immunohistochemistry. SIV-infected cells were found in the genital tract of 13 of the 16 animals examined, and in most cases the SIV-infected cells were located in the submucosa of the cervix and vagina. However, SIV-infected cells were also found in the vaginal epithelium. SIV-infected cells were more common in sites of inflammation than in normal areas. These findings suggest that SIV gains access to genital tract secretions from the cervix and vaginal epithelium. PMID- 1519671 TI - Antigenic heterogeneity of vascular endothelium. AB - The antigenic status of vascular endothelium from different sites of the normal adult and fetal human cardiovascular system was investigated. Tissues included aorta (n = 9), pulmonary artery (n = 8), coronary artery (n = 6), ventricle/atrium (n = greater than 10), lymph node (n = 2), fetal whole heart (n = 3), and umbilical cord (n = 7). Frozen sections were studied using monoclonal antibodies recognizing endothelial markers (EN4, vWf, Pal-E, and 44G4), vascular adhesion molecules (ICAM-1, ELAM, VCAM, and PECAM), the monocyte/endothelial marker (OKM5), and major histocompatibility complex (MHC) molecules (class I and class II). Results demonstrate that capillary endothelium is phenotypically different from endothelial cells (EC) lining large vessels. Capillary EC strongly express MHC classes I and II, ICAM, and OKM5, which are variably weak to undetectable on large vessels. In contrast, the large vessels strongly express vWf and appear to constitutively express ELAM-1. This suggests that the capillary EC may be more efficient at antigen presentation or more susceptible to immune attack in vivo. Interestingly, normal coronary arteries, unlike all other large vessels, express MHC class II and VCAM molecules. Future studies should concentrate on comparative functional studies between capillary, coronary, and large vessel EC. PMID- 1519672 TI - Platelet morphologic changes and fibrinogen receptor localization. Initial responses in ADP-activated human platelets. AB - Platelet exposure to agonists results in rapid morphologic changes paralleled by fibrinogen binding and platelet aggregation. The current study used standardized stereology in conjunction with immunogold electron microscopy to correlate the initial morphologic changes with fibrinogen receptor localization on the surfaces of ADP-activated human platelets. A 45% increase in platelet circumference was observed after 3 seconds of activation (P = 0.001). Virtually all of this increase was due to a 13-fold increase in projection membrane, and the projections observed by stereo microscopy at this time were mostly blunt. Both blunt and long projections also accounted for the increase in platelet-platelet contacts at 10 seconds of activation. Immunogold electron microscopy using the monoclonal antibodies P2 and AP-2 against the fibrinogen receptor, glycoprotein IIb/IIIa (GP IIb/IIIa), showed relatively equivalent immunogold densities on projections compared with cell body during 30 seconds of activation. The activation-dependent anti-GP IIb/IIIa monoclonal antibody, 7E3, showed an immunogold density 37% greater on projections compared with cell body (P = 0.0001). Colocalization studies using 7E3 with a polyclonal antifibrinogen antibody showed bound fibrinogen in close proximity to the GP IIb/IIIa localized by 7E3 on projections. These studies support an important role for platelet projections during the earliest stages of fibrinogen binding and ADP-induced aggregation. PMID- 1519673 TI - Helicobacter pylori. Its role in the pathogenesis of peptic ulcer disease in a new animal model. AB - The association and causative role of Helicobacter pylori infection of the stomach with gastric ulcer, duodenal ulcer, non-ulcer dyspepsia, and gastritis has remained controversial. The authors studied the effects of daily intragastric administration of H. pylori suspension in saline (10(8) CFU/ml) and bacteria-free filtrates of saline H. pylori suspensions in 85 Sprague-Dawley rats (weight, 150 to 200 g) with normal mucosa and with surgically produced experimental gastric ulcers. Group I rats (n = 30) with pre-existent experimental gastric ulcers received H. pylori suspension (ATCC 43504, 10(8) CFU/ml); Group II rats (n = 20) with experimental gastric ulcers received bacteria-free H. pylori filtrates; Group III rats with ulcers (n = 20) received saline alone; and Group IV control rats (n = 15) without ulcers received intact H. pylori organisms in suspension (ATCC 43504, 10(8) CFU/ml). At death, ulcer surface areas were measured with a dissecting microscope. Full-thickness sections were obtained for quantitative and qualitative histologic parameters, including the area of remaining mucosal necrosis; characteristics and cellular composition of restored mucosal architectures; and presence or absence of inflammation including counts of neutrophils and lymphocytes. H. pylori organisms were identified within the surface mucus and crypts using routine, special, and immunohistochemical stains. Our results indicate that the continued presence of either intact H. pylori organisms or bacteria-free H. pylori filtrates in the stomachs of rats with pre existent gastric ulcers resulted in delayed healing of the ulcers and persistence of chronic active inflammation. Daily administration of suspensions of H. pylori organisms to sham-operated rats with intact gastric mucosa, however, resulted in no ulceration or inflammation despite identification of surface H. pylori organisms at death. The authors conclude that H. pylori alone causes little or no effect on an intact gastric mucosa in the rat, that either intact organisms or bacteria-free filtrates cause similar prolongation and delayed healing of pre existing ulcers with active chronic inflammation, and that the presence of predisposing factors leading to disruption of gastric mucosal integrity may be required for the H. pylori enhancement of inflammation and tissue damage in the stomach. PMID- 1519674 TI - The eSS rat. A model of non-insulin-dependent human diabetes. PMID- 1519675 TI - Steroid anaesthesia. PMID- 1519676 TI - Pregnanolone: a new steroid intravenous anaesthetic. Dose-finding study. AB - The intravenous steroid anaesthetic pregnanolone has been investigated as an induction agent in 60 fit adults premedicated with morphine and atropine. The drug was given in a stepwise fashion starting with 0.5 mg.kg-1; following a successful induction, the next patient received 15% less, while the subsequent patient received 15% more if anaesthesia was not achieved. Taking loss of eyelash reflex as the end point, 31 patients were satisfactorily induced; the AD50 in these patients was 0.44 mg.kg-1 (95% CI 0.41-0.47). A further 23 patients were induced satisfactorily as assessed by cessation of counting. Induction was trouble free with minimal changes in heart rate and arterial blood pressure, a low incidence of apnoea and few involuntary movements; pain on injection was not a feature. Loss of eyelash reflex is not a good end point for assessment of loss of consciousness following pregnanolone. PMID- 1519677 TI - Tramadol: pain relief by an opioid without depression of respiration. AB - Two independent clinical trials were conducted simultaneously. In one, tramadol and pethidine were compared in 30 patients by patient-controlled analgesia during the first 24 h following abdominal surgery. The mean 24 h consumption of tramadol and pethidine was 642 mg and 606 mg respectively, giving a potency estimate of tramadol relative to pethidine of 0.94 (95% confidence interval 0.72-1.17). In the second trial, the effect on respiration of three doses of tramadol (0.5, 1.0, and 2.0 mg.kg-1) was compared with that of morphine sulphate (0.143 mg.kg-1) by intravenous injection during stable halothane anaesthesia. At approximately 1.5 times the equipotent dose, as estimated from the first trial, tramadol transiently depressed the rate of respiration but had no effect on end-tidal carbon dioxide tension. Morphine caused apnoea or considerable depression of ventilation. The results suggest that mechanisms other than opioid receptor activity play a significant role in the analgesia produced by tramadol. PMID- 1519678 TI - Gastric emptying after minor gynaecological surgery. The effect of anaesthetic technique. AB - Gastric emptying was measured using the paracetamol absorption method in 30 patients immediately after a general anaesthetic for minor gynaecological surgery and in 10 female controls. Anaesthesia was induced with either propofol alone, propofol and alfentanil (4.5 micrograms.kg-1) or propofol and fentanyl (1.4 micrograms.kg-1) and maintained with intermittent propofol and 66% nitrous oxide in oxygen. Gastric emptying was delayed significantly in all patient groups when compared with volunteers. However, the delay in gastric emptying was similar in the three patient groups. PMID- 1519679 TI - Cardiovascular responses to insertion of the laryngeal mask. AB - We have compared, in 40 healthy patients, the cardiovascular responses induced by laryngoscopy and intubation with those produced by insertion of a laryngeal mask. Anaesthesia was induced with thiopentone and maintained with enflurane and nitrous oxide in oxygen; vecuronium was used for muscle relaxation. Arterial pressure was measured with a Finapres monitor. The mean maximum increase in systolic arterial pressure after laryngoscopy and tracheal intubation was 51.3% compared with 22.9% for laryngeal mask insertion (p less than 0.01). Increases in maximum heart rate were similar, (26.6% v 25.7%) although heart rate remained elevated for longer after tracheal intubation. We conclude that insertion of the laryngeal mask airway is accompanied by smaller cardiovascular responses than those after laryngoscopy and intubation and that its use may be indicated in those patients in whom a marked pressor response would be deleterious. PMID- 1519680 TI - The relationship between the concentration of temazepam in cerebrospinal fluid and sedation in man. AB - Twenty-six patients received oral temazepam and subsequently spinal anaesthesia. Blood and lumbar cerebrospinal fluid temazepam levels were measured together with the degree of sedation. The plasma and cerebrospinal fluid concentrations correlated well with the temazepam dose but even better with the weight standardised dose (r = 0.65, p = 0.0003 and r = 0.75, p = 0.00001 respectively). Both the plasma and cerebrospinal fluid concentrations of temazepam were correlated with the patient's sedation (r = 0.42 p = 0.037, and r = 0.46 p = 0.021 respectively), but neither was strong. Thus, although the drug concentration at the receptor may be a major factor in producing sedation, other factors, possibly the receptor population or their responsiveness, are also important contributors. PMID- 1519681 TI - Peroperative arterial hypoxaemia. The interaction between intrapulmonary shunt and cardiac output. A computer model. AB - A computer model of respiratory physiology was used to investigate the interaction between cardiac output and intrapulmonary shunting during anaesthesia. Significant degrees of arterial desaturation were demonstrated as the cardiac output was reduced. We suggest that volume expansion may correct some episodes of desaturation observed during anaesthesia. PMID- 1519682 TI - A nasal CPAP system. Description and comparison with facemask CPAP. AB - Nasopharyngeal pressures were compared in eight subjects breathing through either a nasal CPAP system or facemask CPAP system at a fresh gas flow of 50, 75 and 100 l.min-1. During nose breathing there was no significant difference in nasopharyngeal pressure between the two systems. During mouth breathing pressures were significantly lower with nasal CPAP. During nose breathing at 75 l.min-1 the mean inspiratory and expiratory pressures in cmH2O (SD) were 3.4 (0.68) and 5.9 (0.55) for nasal CPAP and 3.3 (0.71) and 6.3 (0.73) for facemask CPAP. The respective pressures during mouth breathing were 0.3 (0.73) and 2.9 (1.74) for nasal CPAP and 3.9 (0.73) and 5.8 (0.82) for facemask CPAP. PMID- 1519683 TI - Nasal CPAP after coronary artery surgery. AB - Two groups of 14 patients were compared after coronary artery bypass surgery where the left internal mammary artery had been used as a conduit. One group received nasal continuous positive airway pressure for 1 h, the other group acted as a control. Mean pulmonary shunt fraction was 16.3% before, 12.6% during and 15.7% after continuous positive airways pressure. In the control group the shunt fraction fell from 17.3% to 16.8%. The reduction in shunt fraction was significantly greater with nasal continuous positive airways pressure than in the control group (p = 0.016). There was a significant reduction (p = 0.025) in respiratory rate from 18.3 to 16.7 breath.min-1 during continuous positive airway pressure. Other measured cardiorespiratory variables did not differ significantly between the groups. Visual analogue scores showed no significant difference in chest pain or mask comfort between the groups. The ease of breathing score was, however, significantly better in the continuous positive airways pressure group, 7.5 (SD 1.8) cm and control 5.6 (SD 2.6) cm. PMID- 1519684 TI - The effect of nitrous oxide on laryngeal mask cuff pressure. In vitro and in vivo studies. AB - We have studied the effect of nitrous oxide on the cuff pressure of a laryngeal mask both in vitro and in vivo. In laboratory tests, we showed that nitrous oxide and carbon dioxide diffuse across the cuff wall much more rapidly than nitrogen and oxygen. Differing partial pressures of these gases across the cuff wall therefore give rise to changes in volume and pressure within the cuff. We then studied 18 patients undergoing general anaesthesia with nitrous oxide, and found a consistent and linear increase in cuff pressure in all patients. After 30 min, the mean pressure had increased by 30 mmHg, and there was approximately 10% nitrous oxide in the cuff. It is difficult to relate these findings to pressure on pharyngeal structures, but methods of limiting the rise in intracuff pressure are discussed. PMID- 1519685 TI - Topical nonsteroidal anti-inflammatory gel for the prevention of peripheral vein thrombophlebitis. A double-blind, randomised, placebo-controlled trial in normal subjects. AB - A double-blind, randomised, placebo-controlled study was undertaken to determine whether topical application of a nonsteroidal anti-inflammatory gel to skin overlying peripheral vein cannula sites has a role in reducing the incidence or delaying the onset of peripheral vein thrombophlebitis. Fifty normal subjects had intravenous cannulae placed in right and left arms. Subjects were randomised to receive twice daily application of either active nonsteroidal anti-inflammatory gel or placebo gel to each cannula site. Cannula sites were observed and signs and symptoms of inflammation recorded up to 108 h. If any site had signs extending beyond 2 cm then the cannula was removed. Cannula sites that had 'active' gel applied had half the incidence of marked signs at 108 h (44% vs 22%, p less than 0.05). These results suggest that local application of topical nonsteroidal anti-inflammatory gel to cannula sites may have a significant role to play in the prevention of peripheral vein thrombophlebitis. PMID- 1519686 TI - Preparation of the critically ill for interhospital transfer. AB - Changes in monitoring and therapy during the preparation of 100 critically ill patients for interhospital transfer by a specialist team were documented prospectively with the aim of providing guidelines for nonspecialists. Severity of illness scores were recorded before and after preparation. Median duration of preparation for ambulance journeys was 50 min and for aeroplane journeys was 82 min. During preparation, a portable electrocardiogram and pulse oximeter were attached to 21 and 76 patients respectively and intra-arterial pressure monitoring was continued or instituted in 88 patients. Supplemental oxygen and intravenous fluids were the therapies most commonly increased or instituted by the transport team; mechanical ventilation, positive end-expiratory pressure and inotropic drugs were increased or instituted less frequently. Median therapeutic intervention scores before and after preparation were 21 and 23 respectively, highlighting the need to increase rather than withdraw support for transfer. PMID- 1519687 TI - A clinical evaluation of the 'Rapitrach'. A bedside percutaneous tracheostomy technique. AB - A number of percutaneous tracheostomy devices are now available commercially. We report a preliminary clinical study of the use of the 'Rapitrach' kit (Fresenius, Runcorn, Cheshire, UK). Twenty critically ill adult patients underwent tracheostomy using the kit. Nineteen of the procedures were carried out at the bedside in the intensive therapy unit. Correct tube placement was achieved in all cases. PMID- 1519688 TI - Nosocomial sinusitis in ventilated patients. Nasotracheal versus orotracheal intubation. AB - A total of 68 postoperative patients whose lungs were ventilated for more than 4 days were studied prospectively during a one-year study period to investigate the effect of the mode of intubation on the paranasal sinuses. After an initial X ray of the skull showing no pathological findings, patients were assigned randomly to one of the study groups; the lungs of patients in group A were ventilated via an orotracheal tube (n = 32), and patients in group B via a nasotracheal tube (n = 36). X ray examinations of the sinuses were performed at regular intervals. Diagnosis of sinusitis was confirmed by transantral needle puncture and culture of fluids obtained. Antibiotic regimens were altered according to laboratory testing. Two patients in group A developed signs of sinusitis in comparison to 15 patients in group B (p less than 0.01). However, there were significantly more airway complications in the orotracheal group, particularly during the period of weaning from ventilation. We conclude that orotracheal intubation should be preferred as the routine route of intubation. PMID- 1519689 TI - Neurological sequelae in children after prolonged propofol infusion. PMID- 1519690 TI - Resistance and additional inspiratory work imposed by the laryngeal mask airway. A comparison with tracheal tubes. AB - Laryngeal mask airways and tracheal tubes were studied to determine both their resistance to constant gas flows and additional inspiratory work during simulated inspiration. Laryngeal mask airways imposed less resistance and required lower additional inspiratory work compared with the corresponding sized tracheal tubes. If inspiratory loading during anaesthesia is an important consideration, then the laryngeal mask airway may be preferable to a tracheal tube. PMID- 1519691 TI - Measurement of forces during laryngoscopy. AB - The forces transmitted by the laryngoscope blade onto the base of the tongue are assumed to be a major cardiovascular stimulus. This study investigates the various forces applied onto a Macintosh laryngoscope during laryngoscopy. The forces acting along the axis of the handle are described, as well as the forces exerted by the anaesthetist to prevent the laryngoscope from turning. Based on a relatively simple technique, a modified laryngoscope has been designed to measure these forces. Four different laryngoscopic parameters are determined: (1) the duration of laryngoscopy, (2) the maximally applied force, (3) the mean force and (4) the integral of the force over the time (area under the curve). The force measurements of 49 anatomically normal patients undergoing uncomplicated intubation are included in the study. The duration of laryngoscopy was 16.3s (SD 11.8), the applied peak force was 35N (SD 12) and mean force necessary was 20N (SD 6) while the force-time integral was 324N (SD 194). PMID- 1519692 TI - Personal experience of three commonly used methods of postoperative pain relief. PMID- 1519693 TI - Pre-operative paravertebral block for peri-operative analgesia. PMID- 1519694 TI - Pattern of use of the laryngeal mask airway. PMID- 1519695 TI - Defective feed mount. PMID- 1519696 TI - Propofol for sedation in intensive care in a patient with an acute porphyric attack. PMID- 1519697 TI - Failed tracheal intubation. PMID- 1519698 TI - Propofol and mono-amine oxidase inhibitors. PMID- 1519699 TI - A malformed guidewire. PMID- 1519700 TI - Basic life support performance. PMID- 1519701 TI - 'Slipped' trachea during laryngo-oesophagectomy. PMID- 1519702 TI - Exaggerated epidural blockade? PMID- 1519704 TI - Measurement of VAS pain scores with a 'magic screen'. PMID- 1519703 TI - Missing O-ring causes unrecognised large gas leak. PMID- 1519705 TI - The potential hazards of using iodine as an antiseptic solution. PMID- 1519706 TI - Anaphylactoid reaction to ranitidine in an obstetric patient. PMID- 1519707 TI - The upside down facemask again. PMID- 1519708 TI - 'On/off' switches on anaesthetic machines. PMID- 1519709 TI - Local anaesthesia for reduction of neonatal inguinal hernia. PMID- 1519710 TI - Splitting tubes. PMID- 1519711 TI - Doxapram after general anaesthesia. PMID- 1519712 TI - Anaesthetists, nurses, and pre-operative visiting. PMID- 1519713 TI - Low dose amitriptyline in the treatment of chronic pain. AB - The analgesic efficacy of amitriptyline 25 mg was compared with placebo in 41 patients with chronic (more than 3 months) nonmalignant pain, using a double blind randomised multiple-dose 3-week treatment period crossover design. Amitriptyline 25 mg provided significantly greater efficacy than placebo, with significant differences evident within the first week. There was no significant difference on mood scores between amitriptyline and placebo. The results suggest that surprisingly low doses of amitriptyline may be effective without substantial adverse effects, that the effect is evident early, and that the effect is distinguishable from any effect of the amitriptyline on mood. PMID- 1519714 TI - Phenytoin reduces suxamethonium-induced myalgia. AB - A prospective, randomised trial was undertaken in 60 healthy adults to determine the efficacy of intravenously administered phenytoin in doses of 5 mg.kg-1 for the prevention of suxamethonium-induced fasciculations, a rise in serum K+ and myalgia. This was compared with tubocurarine pretreatment and no pretreatment (control group). Phenytoin pretreatment significantly reduced myalgia from 45% (nine patients) in the control group to 10% (two patients) (p less than 0.05). It also decreased the duration and mean intensity of fasciculations. Incidentally, phenytoin was also found to decrease significantly mean serum Na+ levels (p less than 0.001) both at 5 and 20 min after administration. Tubocurarine pretreatment (3 mg) resulted in a significant decrease in fasciculations, but myalgia, which occurred in five patients, remained the same. No significant correlation was found between muscle fasciculations, postoperative myalgia and K+ changes, but patients with myalgia had a significant decrease in mean serum Na+ levels at 5 and 20 min after suxamethonium (p less than 0.01). PMID- 1519715 TI - A comparison of laryngeal mask airway with tracheal tube for intra-ocular ophthalmic surgery. AB - The use of the laryngeal mask was compared with tracheal intubation in 30 patients who underwent intra-ocular ophthalmic surgery and who received intravenous anaesthesia with propofol. Changes in intra-ocular pressure, heart rate and mean arterial pressure after the insertion of the laryngeal mask airway or the tracheal tube were not significantly different. However, at the end of the procedure, a significantly higher percentage of patients with a tracheal tube coughed, reacted to head movement and suffered breath-holding. In addition, significantly more patients in this group complained of a sore throat (p less than 0.05). During intravenous propofol anaesthesia, the laryngeal mask airway does not offer any advantage over tracheal intubation in the control of intra ocular pressure for intra-ocular ophthalmic surgery. However, there were fewer complications immediately following surgery in the laryngeal mask group. PMID- 1519716 TI - A multiple dose comparison of combinations of ibuprofen and codeine and paracetamol, codeine and caffeine after third molar surgery. AB - In a randomised, double-blind, double-dummy, multiple dose, crossover study in 30 patients we compared an ibuprofen/codeine combination (400 mg ibuprofen/25.6 mg codeine phosphate) with a paracetamol/codeine/caffeine combination (1 g paracetamol/16 mg codeine phosphate/60 mg caffeine) for pain relief over 6 days after two-stage bilateral lower third molar removal. The ibuprofen combination produced significantly greater analgesia than the paracetamol combination, both on single-dose analysis of the first and second days and on multiple-dose measures for days 1, 2, 3 and 4. The mean incidence of adverse effects over the 6 days was 20% for both combinations. This trial design (crossover with multiple dosing in outpatients) is a sensitive way of testing for analgesia, and is potentially more predictive of adverse effect problems than single-dose studies. It confirms that multiple dosing may show increased efficacy. PMID- 1519717 TI - Upper respiratory tract infections and general anaesthesia in children. Peri operative complications and oxygen saturation. AB - Conflicting reports regarding the hazards of anaesthesia in children presenting for surgery with an upper respiratory tract infection have appeared in the literature. In the present study 130 children undergoing general anaesthesia with face mask for myringotomy and grommet insertion were graded as having either an acute or recent upper respiratory tract infection or were asymptomatic according to predetermined clinical symptoms and signs. The severity of respiratory and related complications were scored during induction, emergence and recovery. The peripheral oxygen saturation was recorded during induction, emergence, transfer to the recovery ward and in the recovery ward itself. There were no significant differences (p greater than 0.05) in the complication scores between the three groups of children. However, the incidence of hypoxaemia (oxygen saturation less than or equal to 93%) was significantly greater during transfer in the acute infection group (p = 0.001) and the recent infection group (p = 0.02), as well as during recovery in the acute group (p = 0.03) compared with asymptomatic children. PMID- 1519718 TI - Patient-controlled sedation using propofol in day surgery. AB - Patient-controlled sedation using propofol was studied in 30 unselected patients aged 26-72 years undergoing day case general surgical or orthopaedic procedures under local or regional anaesthesia. Using a fixed propofol dose of 0.7 mg.kg-1 body weight, the technique provided anxiolysis and sedation with few side effects and a high degree of patient satisfaction. Increasing age was significantly correlated with a deeper maximum level of sedation (p less than 0.001), indicating a need for a lower bolus dose in the higher age groups. Interpatient variability in propofol requirement was reflected in the lack of significant correlation between propofol dose and procedure duration (p = 0.095) and patient age (p = 0.72). PMID- 1519719 TI - The laryngeal mask airway. Two cases of prehospital trauma care. AB - Two cases of emergency prehospital airway control using the laryngeal mask are described. The patients were trapped following road traffic accidents and limited access prevented tracheal intubation. The laryngeal mask airway may be a useful alternative to tracheal intubation in some cases of prehospital trauma care. PMID- 1519720 TI - Failed extradural anaesthesia for caesarean section. Complication of subsequent spinal block. AB - Two cases of unexpected high spinal anaesthesia following failed extradural anaesthesia for Caesarean section are described. In both cases rapid and unexpected advance of blockade, after the subarachnoid injection of moderate doses of local anaesthetic, required tracheal intubation. In one of the cases 15 ml of 0.9% saline, but no local anaesthetic, had been injected into the extradural space, suggesting that the mechanism involved is the cephalad displacement of the cerebrospinal fluid by extradural fluid, and not leakage of extradural anaesthetic solution into the subarachnoid space. PMID- 1519721 TI - An automated system for testing the accuracy of patient-controlled analgesia devices. AB - A system was developed to test the accuracy of patient-controlled analgesia devices in situations simulating clinical use. Bolus requests are made automatically at predetermined intervals, and the infusate delivered is measured and recorded without the need for operator presence. To ensure clinical relevance, the bolus request times used in this study corresponded to a pattern typical of those requested by patients on the ward. Graseby, Abbott Provider 5500 and IVAC patient-controlled analgesia devices were tested and found to deliver reasonably accurately over a 24 h period. However, when an infusion was started in an unprimed system or after a period of no bolus requests in a bolus-only mode the Graseby and IVAC machines under-delivered. This system provides a means of testing patient-controlled analgesia devices operating in any delivery mode. PMID- 1519722 TI - Laryngeal mask and anaesthetic waste gas exposure. AB - In recent years there has been a growing awareness of the possible hazards caused by anaesthetic gases in operating theatres. The laryngeal mask airway provides an alternative both to tracheal intubation and the face mask although the implications for operating theatre contamination have not been quantified. This paper describes the incidence and magnitude of exposure of theatre personnel to waste anaesthetic gases during laryngeal mask airway anaesthesia. The leakage of anaesthetic gases to the anaesthetist's breathing zone was monitored using a Bruel & Kjaer Multi Gas Monitor, Type 1302 during 50 general anaesthetics employing either spontaneous (n = 24) or controlled (n = 26) ventilation. All patients were anaesthetised with propofol, alfentanil and nitrous oxide. There was no statistically significant association between the amount of anaesthetic gas leakage and ventilation method. The laryngeal mask airway meets occupational safety requirements on nitrous oxide concentrations in the operating theatre environment. PMID- 1519723 TI - The upgraded Finapres 2300e. A clinical evaluation of a continuous noninvasive blood pressure monitor. AB - Measurements from the upgraded Finapres 2300e continuous noninvasive blood pressure monitor, the Finapres 2300 and Colin oscillometric noninvasive blood pressure monitor were compared with invasive arterial line blood pressure readings. Fifteen young Chinese patients undergoing elective spinal surgery of more than 2 h duration had contemporaneous blood pressure measurements digitally recorded every minute. Data were analysed using methods described by Bland and Altman to assess agreement of noninvasive devices with an arterial line. Results showed that although the Finapres 2300e was significantly more accurate than the Finapres 2300 and Colin noninvasive blood pressure monitors it could not be recommended as a substitute for continuous arterial line blood pressure monitoring. Both Finapres devices demonstrated reductions in accuracy related to time (drift) and over-read diastolic and mean pressures by 5-8 mmHg throughout the range of mean arterial line pressures (bias). The Colin was consistently less accurate than the Finapress monitors and performed worst at low mean arterial line pressures. PMID- 1519724 TI - Light anaesthesia with propofol for paediatric MRI. AB - Anaesthetic techniques and monitoring equipment may interfere with the technical demands of magnetic resonance imaging. The purpose of this study was to evaluate the safety and efficacy of a light anaesthetic technique with intravenous propofol in nonintubated children. In 20 neuropaediatric patients sedation was induced with propofol 1 mg.kg-1, followed by a continuous infusion titrated to produce adequate immobilisation. Oxygen, 4 l.min-1, was administrated by paediatric face mask. Respiratory rate, end-tidal carbon dioxide tension and oxygen saturation were continuously monitored. In 10 patients capillary blood gas tensions were determined 3 and 20 min after the procedure. Data are reported as mean (SD) and the mean (SD) total propofol dose was 5 (2) mg.kg-1.h-1. Oxygen saturation remained constantly higher than 96% in all patients. End-tidal carbon dioxide tension varied between 35 (7) mmHg 3 min after induction, and 41 (6) mmHg 30 min after the start of the procedure. End-tidal to capillary PCO2 difference was 4 (3) mmHg. Within 20 min after the end of the procedure all patients were fit for dismissal to the ward. One imaging sequence out of 49 was repeated because of movement artefacts. In conclusion, intravenous propofol sedation appears to be a safe and reliable technique for paediatric sedation during magnetic resonance imaging. PMID- 1519725 TI - Dermal patch anaesthesia for venous cannulation with 10% lignocaine gel containing glycyrrhetinic acid monohemiphthalate disodium as an absorption promoter. AB - The clinical efficacy of transdermal 10% lignocaine gel mixture containing 3% w/w glycyrrhetinic acid monohemiphthalate disodium as an absorption promoter was evaluated at venous cannulation in 17 paediatric (6-11 years) and 17 adult (29-65 years) patients. After about 60 min of occlusive application, the mean (SD) pinprick pain score was 0.7 (0.7) in the paediatric group, compared with 1.4 (1.3) in the adults (p less than 0.05). Twenty-five patients (14 children and 11 adults) who had a pinprick score of 0 or 1 underwent venous cannulation without intradermal local anaesthetic. The mean (SD) pain scores at venepuncture showed no significant differences between children and adults. PMID- 1519726 TI - Gastro-oesophageal reflux and hiccough on induction of anaesthesia. PMID- 1519727 TI - Laryngeal mask: a more secure airway than intubation? PMID- 1519728 TI - Hoarseness and the use of the laryngeal mask. PMID- 1519729 TI - Use of the laryngeal mask airway in a patient with Edward's syndrome. PMID- 1519730 TI - Laryngeal mask cuff pressure and nitrous oxide. PMID- 1519731 TI - Hazards of supplementary oxygen. PMID- 1519732 TI - Fatal pulmonary embolus following caesarean section. PMID- 1519733 TI - Difficulty in extubation. PMID- 1519735 TI - Patient lifting systems. PMID- 1519734 TI - Persistent narrowing of an armoured tube. PMID- 1519736 TI - Epidural bupivacaine and diamorphine for postoperative analgesia. PMID- 1519737 TI - Respiratory depression after alfentanil. PMID- 1519738 TI - Evaluation of the E25 for the Level 1 blood warmer. PMID- 1519739 TI - Intra-arterial prilocaine for ischeamia due to radial artery cannulation. PMID- 1519740 TI - Epidural infusion and neuropraxia. PMID- 1519741 TI - Laparoscopy, surgical emphysema and ECG voltage. PMID- 1519742 TI - Anaesthesia for transvenous insertion of an automatic implantable cardioverter defibrillator. PMID- 1519743 TI - The 'nonempty' empty bottle. PMID- 1519744 TI - 'Humbug'. PMID- 1519745 TI - Medical audit--failed intubation in obstetrics. PMID- 1519746 TI - Enzyme-catalyzed oligosaccharide synthesis. AB - Cell-surface carbohydrates and their conjugates are involved in many types of molecular recognition. This review describes recent developments in enzyme catalyzed oligosaccharide synthesis, with particular focus on glycosyltransferase and glycosidase reactions. With the increasing availability of glycosyltransferases via recombinant DNA technology, glycosyltransferase catalyzed glycosylation with in situ regeneration of sugar nucleotides appears to be the most effective method for large-scale stereocontrolled oligosaccharide synthesis. PMID- 1519747 TI - Determination of the intravesicular ionized sodium concentration in a cell-free brain membrane vesicle preparation using the fluorescent indicator, SBFI. AB - The intravesicular ionized Na concentration (Nai) was measured using the fluorescent Na indicator, SBFI, in microsacs, a cell-free brain vesicle preparation. SBFI fluorescence was monitored by a dual excitation-wavelength method at the same wavelengths commonly employed for Fura-2 determination of intracellular ionized calcium concentrations (Cai). Calibration of SBFI fluorescence was reliably performed in brain microsacs in situ. Resting Nai was dependent on the extravesicular Na concentration (Nao) and was about 36 mM in the presence of 120 mM extracellular Nao. In the presence of ouabain, an inhibitor of the plasma membrane Na/K-ATPase, Nai increased by 27 mM over 60 s. Nai was also increased by resuspension of microsacs in buffers of low free Ca concentrations (0 to 0.8 mM), indicating that the extravesicular Ca concentration (Cao) is an important regulator of Nai. Alkaloids active at voltage-sensitive Na channels, veratridine and aconitine, also increased Nai. These results demonstrate the presence of homeostatic mechanisms for neuronal Nai regulation and show that Nai can be measured in a cell-free brain vesicle preparation using SBFI. PMID- 1519748 TI - Determination of the molar absorptivities of phenothiazine cation radicals generated by oxidation with hydrogen peroxide/peroxidase. AB - Phenothiazines are used as antipsychotic drugs and as reagents to determine microamounts of hemoglobin in biological fluids and tissues. Several agents cause the oxidation of phenothiazines to chromophoric cation radicals, whose stability may be related with their biological action. Enzymes and proteins with peroxidase activity catalyze the oxidation by H2O2 of phenothiazines to their corresponding cation radicals, which suffer a nonenzymatic breakdown. The instability of these cation radicals makes the determination of their respective molar absorptivities very difficult. These properties, however, have been determined for a few phenothiazine cation radicals by cumbersome or unreliable procedures. In this paper a new method is proposed and applied to six different phenothiazines oxidized with H2O2/peroxidase. The method involves the stoichiometric exhaustion of H2O2, under assay conditions which yield a fast enzymatic formation of phenothiazine cation radicals and which slow down their nonenzymatic breakdown. This method may be useful for quantitative studies on the enzymatic activity and the reaction mechanism of the oxidation of a number of phenothiazines catalyzed by different types of peroxidase, as well as by proteins with peroxidase activity, such as hemoglobin. PMID- 1519749 TI - Interpretation of the thiobarbituric acid reactivity of rat liver and brain homogenates in the presence of ferric ion and ethylenediaminetetraacetic acid. AB - The thiobarbituric acid (TBA) reactivity of rat liver and brain homogenates was characterized to elucidate what kinds of aldehyde species contributed to the reactivity. Characteristic pH dependence of the reactivity with a maximum at around pH 3 and marked enhancement of the reactivity by t-butyl hydroperoxide (t BuOOH) and ferric ion were similar to those of alkadienals. The amounts of aldehyde species, including alkadienals determined as 2,4 dinitrophenylhydrazones, were high enough to account for the enhanced reactivity. The reactivity was inhibited by ethylenediaminetetraacetic acid (EDTA) but not completely, suggesting the presence of malonaldehyde whose reactivity was not affected by EDTA. The amounts of malonaldehyde determined as 1-(2,4 dinitrophenyl)pyrazole could account for a part of the reactivity in the presence of EDTA. Hence, the TBA reactivity of liver and brain homogenates at around pH 3 in the presence of t-BuOOH and ferric ion may be accounted for by alkadienals and malonaldehyde and that in the presence of EDTA by malonaldehyde. PMID- 1519750 TI - An assay for cocaethylene and other cocaine metabolites in liver using high performance liquid chromatography. AB - Cocaethylene (benzoylecgonine ethyl ester or ethyl cocaine) is a transesterification product of cocaine and ethanol that has been observed in the urine of individuals using these drugs in combination. There is evidence that cocaethylene is pharmacologically active, and its formation in vivo may contribute to the toxicity of cocaine. A new method is presented here which enables the quantification of cocaethylene and cocaine, as well as the cocaine metabolites benzoylecgonine and norcocaine in liver tissue. This method utilizes high-performance liquid chromatography with uv detection (235 nm), and the propyl ester of cocaine is used as an internal standard. Liver homogenates are first buffered with 0.1 N dibasic potassium phosphate (pH 9.1) and then extracted with methylene chloride:isopropanol (9:1). Extraction efficiencies were approximately 75-85% for the compounds of interest. The coefficient of variation for replicate determinations (N = 10) of cocaethylene concentration was 5.75%, with comparable values obtained for cocaine, norcocaine, and benzoylecgonine. The detection limit for cocaethylene, based on a peak height threefold greater than background noise, was approximately 1.7 ng of injected compound. Using this method, it was demonstrated that cocaethylene is present in mouse liver following cocaine and ethanol administration, with an apparent rapid rate of formation and elimination. PMID- 1519751 TI - Rapid robust separation of hydroxyproline and proline. AB - The presence of hydroxyproline, and the determination of the ratio of the secondary amino acids proline to hydroxyproline, in amino acid hydrolysates specifically identifies collagen and collagen peptides. o-Phthalaldehyde, and then 9-fluorenylmethyl chloroformate, were used to carry out sequential prederivatization of amino acid hydrolysates in an in-line high-performance liquid chromatography sample loop. After derivatization, reversed-phase high performance liquid chromatography with a C-18 ODS Hypersil cartridge column was used to resolve the hydroxyproline and proline from all primary amino acids, with resolution and detection of hydroxyproline and proline within 2.0 and 2.8 min, respectively, at concentrations in the range of picomoles per microliter of derivatized amino acid. The assay has a turnaround time of 10.75 min. PMID- 1519752 TI - Assessment study on the high-performance liquid chromatography-type hydroxyapatite chromatography in the presence of sodium dodecyl sulfate. AB - The HPLC-type hydroxyapatite chromatography in the presence of sodium dodecyl sulfate (SDS) was assessed with special attention to the behavior of the surfactant. A significant amount of SDS was found to be adsorbed to the hydroxyapatite packed in the column from the starting buffer, 50 mM sodium phosphate buffer, pH 7.0, only when the buffer contained SDS in a concentration at or above its critical micelle concentration. When the phosphate buffer concentration was increased while the SDS concentration was kept at 1 mg/ml, the adsorbed surfactant was desorbed in advance of the release of proteins. Polypeptides derived from proteins could be successfully separated only when the column had been thoroughly equilibrated with the above-mentioned starting buffer solution. When a protein polypeptide complexed with SDS, which had been similarly equilibrated, was applied to the column, an amount of SDS corresponding to 75-90% (w/w) of the surfactant originally bound to the polypeptide was released upon its binding to the hydroxyapatite. On the other hand, porin, an Escherichia coli outer membrane protein, retaining its trimeric native structure in the presence of SDS, released a significantly smaller amount of SDS. When the membrane protein was denatured to give a single polypeptide, it behaved in a manner similar to that of the other protein polypeptides. The mechanism of binding of the protein polypeptides was discussed on the basis of these results. The native and denatured entities of porin could be efficiently separated as the result of the difference in their mode of interaction with the hydroxyapatite. PMID- 1519753 TI - Computer-assisted tracking of actin filament motility. AB - In vitro motility assays, in which fluorescently labeled actin filaments are propelled by myosin molecules adhered to a glass coverslip, require that actin filament velocity be determined. We have developed a computer-assisted filament tracking system that reduced the analysis time, minimized investigator bias, and provided greater accuracy in locating actin filaments in video images. The tracking routine successfully tracked filaments under experimental conditions where filament density, size, and extent of photobleaching varied dramatically. Videotaped images of actin filament motility were digitized and processed to enhance filament image contrast relative to background. Once processed, filament images were cross correlated between frames and a filament path was determined. The changes in filament centroid or center position between video frames were then used to calculate filament velocity. The tracking routine performance was evaluated and the sources of noise that contributed to errors in velocity were identified and quantified. Errors originated in algorithms for filament centroid determination and in the choice of sampling interval between video frames. With knowledge of these error sources, the investigator can maximize the accuracy of the velocity calculation through access to user-definable computer program parameters. PMID- 1519754 TI - Spectrofluorometric assay for the quantitation of cell-tissue electrofusion. AB - Fluorometric assay for quantitating electrofusion, FAQE, was developed to measure the number of cells fused to intact tissue. The fluorescent vital dye hydroethidine is used in this method. The fluorescent intensity detected in the cell tissue hybrids is proportional to the number of individual cells fused. The number of cells fused was determined after fusion by lysing the epithelial layer with 0.2% sodium dodecyl sulfate and the supernatant fluids were measured in a spectrofluorometer and compared to established standard curves. The mean number of cells fused, in five separate experiments, was determined to be approximately 5000. All the experimental corneas had approximately the same number of fused cells with less than 10% variation. In addition, the technique was used to demonstrate an increase in the number of cells fused when multiple fusions were applied to the cell-tissue electrofusion system. These results demonstrate that FAQE can be utilized to quantitatively analyze the fusion yields. PMID- 1519755 TI - New vectors for high level expression of recombinant proteins in bacteria. AB - A system has been developed for synthesis and rapid purification of recombinant polypeptides expressed in frame with glutathione S-transferase (D. B. Smith and K. S. Johnson, 1988, Gene 67, 31-40). Expressed fusion proteins are purified from bacterial extracts by glutathione-agarose affinity chromatography. A thrombin protease cleavage site allowed for proteolysis of the fusion protein. We reported the construction of the vector pGEX-KG (K. Guan and J. E. Dixon, 1991, Anal. Biochem. 192, 262-267) which has a glycine-rich "kinker" immediately after the thrombin cleavage site. This kinker dramatically improved the thrombin cleavage efficiency of several fusion proteins. One potential drawback of expressing proteins in this vector is that, following proteolytic cleavage, unrelated amino acids from the vector remain at the amino terminus of the released protein. These extensions could affect enzymatic activity or protein structure. We have constructed two new vectors, pGEX-KT and pGEX-KN, which have the glycine kinker placed N-terminal to the thrombin cleavage site in order to minimize the unrelated amino acids associated with the cleaved protein. The change in location of the kinker had no effect on the increased thrombin cleavage efficiency. A strategy combining the kinker in the vector pGEX-KN with polymerase chain reaction has also been developed to express fusion proteins which when cleaved with thrombin released a protein having no amino terminal extensions of any kind. PMID- 1519756 TI - Solid-phase extraction of urinary 11-dehydrothromboxane B2 for reliable determination with radioimmunoassay. AB - In this paper we elaborate a one-step procedure for the selective extraction of urinary 11-dehydrothromboxane B2 on octylsilyl silica cartridges for reliable determination with radioimmunoassay. The immunoreactivity profile of nonselectively extracted urine after HPLC separation showed that as much as 70% of the total 11-dehydrothromboxane B2 immunoreactivity comigrates with polar interfering material. Its amount could be considerably decreased using acetonitrile:water (18:82, v/v) as wash solvent before elution of 11 dehydrothromboxane B2 from the cartridge. Alternatively, very high immunoreactive purity was achieved without the preceding wash step by selective elution of the analyte with dichloromethane:hexane (70:30). After both optimized steps in the extraction procedure were combined, immunoreactivity was found only in HPLC fractions corresponding to the retention volume of authentic 11 dehydrothromboxane B2. The homogeneity of this immunoreactivity was confirmed by two-step HPLC separation. A significant correlation of values was observed between samples measured after extraction and those measured after subsequent HPLC purification. A high correlation was also found with concentrations determined by radioimmunoassay using four different antisera. The values of 24 h excretion of 11-dehydrothromboxane B2 in 10 male volunteers (595 +/- 114 ng/g creatinine, mean +/- SD) as well as the inhibitory effect of acetylsalicylic acid (80 +/- 13%) closely correspond with those reported in the literature. This selective extraction procedure provides a high validity in radioimmunoassay without requiring any further purification step. PMID- 1519757 TI - Improvement in the method of sample stacking for gravity injection in capillary zone electrophoresis. AB - A method that allows capillary electrophoresis to be used as a microconcentrating technique is presented. An 85-fold improvement in the amount of material that can be injected into a capillary column without loss of resolution is shown. The method can be used for negative- and positive-charged species but it cannot be used for both species simultaneously. PMID- 1519758 TI - A cell-based assay for evaluating the interaction of heparin-like molecules and basic fibroblast growth factor. AB - A simple panning procedure that allows for the evaluation of interactions between various heparin-like molecules and basic FGF has been developed. This assay measures the ability of compounds to inhibit the interaction of transfected human lymphoblastoid cells, UC 729-6 (UC cells), expressing hamster syndecan and basic FGF-coated plastic plates. The transfected cells bind rapidly to basic FGF-coated plates while the control cells do not bind well. Binding of the transfected cells to basic FGF was inhibited by heparin and heparin sulfate (HS), but not by chondroitin sulfate, dermatan sulfate, keratan sulfate, and hyaluronic acid. There was little inhibition of binding by chemically modified heparin such as completely desulfated, N-acetylated heparin, completely desulfated, N-sulfated heparin, and N-desulfated, N-acetylated heparin. These results suggested that both the N-sulfate and O-sulfate groups of heparin are required for binding to basic FGF. In addition, inhibition by oligosaccharides derived from depolymerized heparin increased with fragment size; partial inhibition was observed with oligosaccharides as small as hexamers. The biochemical basis for the binding of transfected cells to basic FGF was established by showing a significant increase of 35SO4 incorporation into HS. In particular, the level of 35SO4-HS in the trypsin-releasable (cell surface) pool increased fivefold. This increase was accounted for by demonstration of the presence of HS on immunoprecipitated syndecan from the transfected cells. PMID- 1519759 TI - Fluorescence lifetime imaging. AB - We describe a new fluorescence imaging methodology in which the image contrast is derived from the fluorescence lifetime at each point in a two-dimensional image and not the local concentration and/or intensity of the fluorophore. In the present apparatus, lifetime images are created from a series of images obtained with a gain-modulated image intensifier. The frequency of gain modulation is at the light-modulation frequency (or a harmonic thereof), resulting in homodyne phase-sensitive images. These stationary phase-sensitive images are collected using a slow-scan CCD camera. A series of such images, obtained with various phase shifts of the gain-modulation signal, is used to determine the phase angle and/or modulation of the emission at each pixel, which is in essence the phase or modulation lifetime image. An advantage of this method is that pixel-to-pixel scanning is not required to obtain the images, as the information from all pixels is obtained at the same time. The method has been experimentally verified by creating lifetime images of standard fluorophores with known lifetimes, ranging from 1 to 10 ns. As an example of biochemical imaging we created life-time images of Yt-base when quenched by acrylamide, as a model for a fluorophore in distinct environments that affect its decay time. Additionally, we describe a faster imaging procedure that allows images in which a specific decay time is suppressed to be calculated, allowing rapid visualization of unique features and/or regions with distinct decay times. The concepts and methodologies of fluorescence lifetime imaging (FLIM) have numerous potential applications in the biosciences. Fluorescence lifetimes are known to be sensitive to numerous chemical and physical factors such as pH, oxygen, temperature, cations, polarity, and binding to macromolecules. Hence the FLIM method allows chemical or physical imaging of macroscopic and microscopic samples. PMID- 1519760 TI - The use of a layering technique for enhancing stability of lyophilized reagents. AB - An enzyme-mediated assay has been developed for the measurement of salicylate using salicylate monooxygenase purified from Pseudomonas cepacia ATCC 29351. Two assay formulations were produced, based on either a multiple-reagent or a single reagent formulation, to allow sufficient flexibility for automated use. The multiple-reagent formulation was especially suited to diagnostic laboratories performing infrequent manual salicylate estimation where stability of the reconstituted reagent is of paramount importance. This was achieved by preparing the enzyme and color reagents in separate vials, so keeping the enzyme at a stable pH. For more frequent assay use where a reconstituted reagent shelf life was less important, the single-reagent system offers advantages of convenience. However, the working reagent required a pH of 10.0 upon reconstitution. Although the enzyme was sufficiently active at this pH to give a reliable assay, its storage stability was poor at pH 10.0, preventing lyophilization of the reagent at a pH suitable for immediate use on reconstitution. This incompatibility was overcome by use of a layering technique. The enzyme was separated from the buffering solution in the same vial by freezing the buffering solution and then overlayering with the enzyme reagent prior to a second freezing cycle and subsequent freeze drying. PMID- 1519761 TI - Determination of evolved 14CO2 in decarboxylase reactions with application to measurement of [14C]oxalic acid. AB - An assay is described for the determination of the radioactive purity of [14C]oxalic acid preparations and the quantity of [14C]oxalic acid in biological samples. In this method oxalate decarboxylase is used to convert oxalate to formate and CO2. The entire procedure is carried out in a scintillation vial. The 14CO2 released in the enzymic reaction is allowed to diffuse off in a fume hood following acidification. Scintillation fluid is added to reacted and unreacted vials and the radioactivity measured. The loss of radioactivity from the reacted versus the unreacted vials provides the quantity of evolved 14CO2. This value is equal to 50% of the [14C]-oxalate (dpm) present. The radioactive purity of four preparations of [U-14C]oxalic acid was 99.0% while a fifth batch had a purity of 88%. A single batch of [U-14C]oxalic acid had a radioactive purity of 99.0% following storage of an aqueous solution, at -20 degrees C for 7 years. Recovery of [14C]oxalic acid from rat fecal extracts was 101.3%. Eight replicate analyses of a [U-14C]oxalic acid preparation gave a coefficient of variation of 0.3%. Following subcutaneous infusion of [U-14C]oxalic acid to rats, 100.2 +/- 2.9%, mean +/- SD, of the 14C in fecal extracts was present as [14C]oxalic acid (n = 10). The procedure provides a rapid, sensitive, and specific method to determine [14C]oxalic acid. It avoids the time consuming and inconvenient procedure for trapping and counting the evolved 14CO2. The approach used to determine the evolved 14CO2 may find application in other radiochemical methods that require its measurement. PMID- 1519762 TI - High-resolution one-dimensional polyacrylamide gel isoelectric focusing of various forms of elongation factor-2. AB - A system for analyzing covalent modifications of elongation factor-2 (eEF-2) by one-dimensional isoelectric focusing in slab polyacrylamide gels is described. Depending on the degree of phosphorylation, four species of eEF-2 could be resolved corresponding to the un-, mono-, bis-, and trisphosphorylated factor. Furthermore, the degree of ADP-ribosylation of the protein could also be assessed by this method. It was also shown that an acidic isoform of eEF-2 exists which appears not to be artifactual and that the relative level of this isoform appeared to vary between different cell types. By Western blotting the gels and using an antibody against eEF-2 it is possible to assess the state of phosphorylation of the factor in cells. PMID- 1519763 TI - Enzyme-linked immunosorbent assay for proteolytically inactivated antithrombin III: use of sodium dodecyl sulfate to eliminate signal due to intact antithrombin III. AB - Antithrombin III (AT-III) is a serine protease inhibitor (serpin) that can be catalytically inactivated by human neutrophil elastase (HNE) without inhibiting HNE activity. As with catalytic inactivation of most serpins, the cleaved form of the inhibitor is difficult to measure in the presence of active inhibitor. One major difference between the cleaved and intact forms of AT-III is that the cleaved form adopts a more stable conformation. Using sodium dodecyl sulfate (SDS), we were able to devise an enzyme-linked immunosorbent assay (ELISA) capable of detecting cleaved AT-III in the presence of intact AT-III. It seems likely that the SDS alters the intact AT-III so that it is not detected in the ELISA. As little as 5 micrograms/ml HNE-cleaved AT-III could be detected when spiked into human plasma; HNE-cleaved AT-III spiked into human plasma at different levels was recovered as expected. Thrombin-cleaved AT-III was also detected using this ELISA. The generation of cleaved AT-III in human plasma by HNE in the presence of heparin could be monitored as well. The cleaved AT-III ELISA is a novel, yet simple way to measure proteolytically inactivated AT-III in the presence of intact AT-III and should be useful for studying the role of proteolytic inactivation of serpins such as AT-III in vivo. PMID- 1519764 TI - Calibration of a Clark-Type oxygen electrode by tyrosinase-catalyzed oxidation of 4-tert-butylcatechol. AB - A procedure for calibrating a Clark-type oxygen electrode is described. This method is based on the oxidation of 4-tert-butylcatechol (TBC) by O2 catalyzed by tyrosinase, to yield 4-tert-butyl-o-benzoquinone (TBCQ). This reaction consumes known amounts of oxygen in accordance with the stoichiometry: 2TBC + O2----2TBCQ + 2H2O and can be used to determine the relation between the oxygen concentration and the oxygen electrode response. TBCQ is very stable in the reaction medium for more than 30 min and shows no significant breakdown, which makes the calibration possible. A kinetic study of the oxidation of 3,4-dihydroxyphenylalanine by tyrosinase using the oxygen electrode is shown to confirm the validity of the calibration method. PMID- 1519765 TI - Determination of selenium in urine by isotope dilution gas chromatography-mass spectrometry using 4-nitro-o-phenylenediamine, 3,5-dibromo-o-phenylenediamine, and 4-trifluoromethyl-o-phenylenediamine as derivatizing reagents. AB - An isotope dilution gas chromatography-mass spectrometry method for selenium determination in urine using 76Se as an internal standard is described. Three different derivatizing reagents, 4-nitro-o-phenylenediamine (NPD), 3,5-dibromo-o phenylenediamine (DBPD), and 4-trifluoromethyl-o-phenylenediamine (TFMPD) were investigated for their gas chromatographic behavior including memory and precision and accuracy of isotope ratio measurements. By these criteria, the performance of these reagents was TFMPD greater than DBPD greater than NPD. Overall precision values of 1 to 7% were observed in determining Se isotope ratios at the 10-ng level, with no significant difference in using any of the three reagents. Memory effect was observed in the order NPD greater than DBPD greater than TFMPD with TFMPD showing no measurable memory effect. Accuracy of the GC-MS method was verified by quantitation of selenium in the NIST freeze dried urine reference material SRM 2670. PMID- 1519766 TI - Ferrous ion oxidation in the presence of xylenol orange for detection of lipid hydroperoxide in low density lipoprotein. AB - A simple and sensitive method for the direct measurement of lipid peroxides in lipoprotein and liposomes is described. The method is based on the principle of the rapid peroxide-mediated oxidation of Fe2+ to Fe3+ under acidic conditions. The latter, in the presence of xylenol orange, forms a Fe(3+)-xylenol orange complex which can be measured spectrophotometrically at 560 nm. Calibration with standard peroxides, such as hydrogen peroxide, linoleic hydroperoxide, t-butyl hydroperoxide, and cumene hydroperoxide gives a mean apparent extinction coefficient of 4.52 x 10(4) M-1 cm-1 consistent with a chain length of approximately 3 for ferrous ion oxidation by hydroperoxides. Endoperoxides are less reactive or unreactive in the assay. The assay has been validated in the study of lipid peroxidation of low density lipoprotein and phosphatidyl choline liposomes. By pretreatment with enzymes known to metabolize peroxides, we have shown that the assay measures lipid hydroperoxides specifically. Other methods for measuring peroxidation, such as the assessment of conjugated diene, thiobarbituric acid reactive substances and an iodometric assay have been compared with the ferrous oxidation-xylenol orange assay. PMID- 1519767 TI - Photochemical amplification for horseradish peroxidase-mediated immunosorbent assay. AB - A new method for lowering the detection limit for a horseradish peroxidase (HRP) label in an enzyme-linked immunosorbent assay (ELISA) is proposed. The method is based on the use of a photochemical reaction of o-phenylenediamine (o-PD) autosensitized oxidation as an enhancement step in ELISA. The assay consists of two successive steps. The first step is a conventional HRP-mediated ELISA, using high-purity o-PD as a substrate. At this step, an o-PD oxidation product, 2,3 diaminophenazine (DAP), is formed in the dark. At the second step, the sample is illuminated at 400-500 nm for several minutes. Under illumination the concentration of DAP is greatly increased, depending on the duration and intensity of irradiation. Providing that the irradiation conditions are standardized, the final DAP concentration is proportional to the concentration of DAP formed by HRP. An ELISA for human carcinoembryonic antigen has demonstrated that the photochemical amplification method allows the detection limit of an assayed antigen to be lowered and the consumption of antibodies to be reduced. At the second step of this assay, the DAP concentration has been increased 50-fold under 4 min of irradiation. PMID- 1519768 TI - A method for directly determining intact recombinant insulin fusion proteins in crude fermentation extracts. AB - In evaluating the purification of genetically engineered human insulin there is no plausible correlation between the yield of expression as determined by SDS PAGE (taking into account all normally occurring losses during the several purification steps) and the actual yield, i.e., the final pure product. The aim of our work was to develop a fast, accurate, and reproducible method for the quantification of the initial yield of the intact insulin fusion protein directly after fermentation and without prior purification of the fermentation product. Therefore, a protocol for efficient tryptic digestion of protease-resistant inclusion bodies was established. The resulting crude peptide mixture was oxidized by performic acid and the insulin A-chain, which contains no cleavage side for trypsin, was quantified by HPLC in the form of a tetrasulfonate derivative to reduce artefacts due to free -SH groups. Compared with SDS-PAGE, this procedure allows sensitive monitoring of possible degradation at the C terminus. Furthermore, quantification of expression products on the basis of the present method will provide better correlation between initial and actual yield. PMID- 1519769 TI - Analysis of degradation of proteins labeled with fluorescein isothiocyanate by Sephadex G-25 affinity chromatography. AB - Fluorescein isothiocyanate (FITC) has strong affinity to Sephadex G-25 gel. Amino acids labeled with FITC were found to have affinity to the gel, their elution from a Sephadex G-25 column being markedly retarded. On the other hand, proteins labeled with FITC had no affinity to the gel and were eluted in the void volume of the column. The affinity of FITC-labeled compounds to a Sephadex G-25 column decreased with increase in their molecular mass. On the basis of these findings, the degradations of various FITC-labeled proteins by disrupted lysosomes in vitro were analyzed using a small Sephadex G-25 column. FITC-labeled degradation products were easily separated from the substrate proteins, and their production was shown to increase with the incubation time and to be suppressed by the proteinase inhibitor leupeptin. This procedure is a simple method for assay of protein degradation and should be useful in analyses of the roles of proteinases in protein degradation. PMID- 1519770 TI - Chromosome variability and germ cell development in the house mouse. AB - Structural heterozygosities of the karyotype have detrimental effects on the meiotic process, resulting very often in impairment of fertility in the carriers. Both male and female germ cell development are affected by chromosomal variability although spermatogenesis seems particularly prone to be affected, probably because of the intrinsic characteristics of the male germ cell cytodifferentiation process (i.e. the histological architecture of the seminiferous epithelium). However, euploid and aneuploid sperm do not seem to differ in the molecular organization of the genome they carry, thus explaining the almost regular capacity to accomplish the first zygotic developmental stages by the aneuploid sperm (aneuploid both for gametogenic genes and for entire chromosomal arms). A survey of the molecular and morphological data available on germ cell development in conditions of chromosomal rearrangement leads to the conclusion that the current hypotheses accounting for this phenomenon can only partly explain it. A working hypothesis is proposed which considers the three dimensional changes (produced by structural heterozygosity) in the spatial order of chromosomes within the nucleus as the primary cause potentially able to trigger distorted functioning of the germ cells. PMID- 1519771 TI - The role of unpaired sex chromosomes in spermatogenic failure. AB - In 1974 Miklos reviewed evidence suggesting an association between sex chromosome pairing failure and spermatogenic arrest. He proposed that distributed over all the chromosomes there are 'meiotic pairing sites' which must be 'saturated' by homologous pairing during pachytene. In unpaired regions these sites are 'activated', and set in motion a process which leads ultimately to the death of the cell. In the present 'extended abstract' we summarize studies we have carried out on XSxraO male mice, that substantiate the main tenets of Miklos' model. Miklos' model is then used as a basis for explaining data we have collected on a large series of XYY male mice. PMID- 1519772 TI - Drosophila spermatogenesis as a model system. AB - Spermatogenesis is very similar throughout the animal kingdom and is probably based on very old evolutionarily principles. Drosophila can serve as a suitable model system to understand the underlying processes. The molecular and ultrastructural data obtained for Drosophila germ cell development can be applied to understanding spermatogenesis in other organisms, including humans. Various methods used in studies of Drosophila spermatogenesis are presented together with observations which exemplify this conclusion. PMID- 1519773 TI - Localization of intrinsic and extrinsic SVS II immunoreactivity in rat spermatozoa. AB - A glycoprotein, designated SVS II, is secreted in an androgen-dependent manner from lateral prostate and seminal vesicles of the rat. The pI of the protein is 10.5 and it has a molecular mass of 49 kDa. F-actin isolated from skeletal and heart muscle is precipitated at a ratio of 2:1 by SVS II. Using a polyclonal rabbit antibody against SVS II, we found an immunoreaction at the head region of rat spermatozoa removed from the vas deferens. In addition, immunoreactive material was observed in the principal piece of the sperm tail in those spermatozoa. We have studied the distribution of SVS II-immunoreactive material in spermatozoa isolated from seminiferous tubules, proximal (efferent ductules), and distal (caudal epididymal duct) epididymis, both in sexually active and inactive rats and found a differential reactivity pattern. Immunoreactivity observed in the principal piece of the sperm tail develops only immediately before spermiation and does not change during the epididymal transit of the spermatozoa. Immunolabelling seen in the head portion is first observed in spermatozoa from proximal epididymis. Simultaneous with its appearance, rhodamine labelled phalloidin, indicating the presence of F-actin, no longer binds to that region. While the immunoreaction of the sperm head is attributed to extrinsic SVS II, added to the sperm head in proximal epididymis, the immunoreactivity of the sperm tail seems to result from a cross reactive intrinsic sperm tail protein that achieves its final structure briefly prior to the onset of spermiation.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1519774 TI - Progesterone induces capacitation in human spermatozoa. AB - Mammalian sperm acrosome reaction is a prerequisite for oocyte fertilization, and to date the mechanisms regulating this event are still unclear. Recent studies have demonstrated that human follicular fluid is able to induce an influx of extracellular calcium and acrosome reaction in capacitated spermatozoa. More recently these effects have been attributed to progesterone. The results of our study demonstrated that progesterone is able to trigger the capacitation, acrosome reaction, and fertilizability in human spermatozoa through a calcium mediated mechanism, suggesting a clinical use of this steroid in the treatment of spermatozoa for the different techniques of assisted fertilization. PMID- 1519776 TI - Human follicular fluid stimulates motility and velocity of washed human sperm in vitro. AB - Human follicular fluid collected by laparoscopic oocyte pick-up during IVF was studied with a computer-assisted semen analyser to evaluate the effect of hFF on human sperm motility and velocity. Freshly ejaculated human sperm were washed with phosphate buffered saline and mixed with either PBS or hFF. At various incubation periods of time, hFF increased both sperm motility and velocity as compared with control (P less than 0.01). After incubation of sperm with hFF at 37 degrees C and 5% CO2 in air for 0, 1, 3, 6, and 12 h, the amplitude increase of motility were 49%, 77%, 330%, 2020%, and 3340% when individual control motility was considered to be 100%. The amplitude increase of curvilinear velocity were 43%, 51%, 67%, 152%, 278%, respectively. Comparison of the motility and velocity of the sperm treated with hFF between 0 and 12 h, showed that hFF preserved both motility and velocity in vitro (P less than 0.01). The stimulatory effect of hFF was retained after boiling at 100 degrees C for 30 min, or after being filtered through Amicon membrane cones, but it disappeared if the hFF had been pre-treated with chymotrypsin. However, hFF did not stimulate the motility and velocity of unwashed sperm in freshly ejaculated human semen. A non dialyzable and heat-stable factor(s) with a molecular weight below 50,000 in hFF may improve and maintain the motility and velocity of washed human sperm. Whether this factor could be used to improve pregnancy rate in assisted reproduction awaits further investigation. PMID- 1519775 TI - Partial characterization of a proacrosin binding protein. AB - All of the acid (pH 4.0) extracted proacrosin from porcine epididymal spermatozoa was found to be tightly associated with a specific protein referred to as the binding protein. A combination of gel filterations and gel electrophoresis revealed that the binding protein is composed of a major 28 kd and a minor 29 kd protein. Both of the proteins were shown to be nonproteolytic by gelatin SDS-PAGE analysis and the amino acid composition analysis of the purified 28 kd protein revealed that it is not related to the proteolytic component of the proacrosinacrosin system. PMID- 1519777 TI - Histological and morphometric studies on the kinetics of germ cells and immature Sertoli cells during human prespermatogenesis. AB - Human prespermatogenesis between the 8th week of pregnancy and six months after birth was studied in testis material of 28 male foetuses from spontaneous abortions and 81 infants who died from sudden infant death. The foetuses and infants were grouped in 10 age groups. A first steep raise in the numbers of germ cells per 20 tubular cross sections from 22.3 in the first group up to 69.5 in group 3 was observed, i.e. up to the end of the 22nd week of pregnancy. Thereafter, a continuous decrease could be observed modulated by a second slighter increase during the first 4 months after birth. The ratio of germ cells and immature Sertoli cells improves from about 1:20 at the beginning to 1:8 in group 3; afterwards it changes in favour of the immature Sertoli cells down to 1:140 at the end of the study. The initial augmentation of germ cells is interpreted as the effect of a first proliferation wave comparable to that of M prospermatogonia in other species. The decrease of germ cells is due to the stop of germ cell proliferation and simultaneous high proliferative activity of the immature Sertoli cells. PMID- 1519778 TI - In vitro systems for prediction of rates of drug clearance and drug interactions. PMID- 1519779 TI - Effect of nitrous oxide on intracranial pressure after cranial-dural closure in patients undergoing craniotomy. AB - After cranial-dural closure, nitrous oxide (N2O) may diffuse into and expand an entrapped volume of intracranial air, thereby increasing intracranial pressure (ICP). We performed a prospective clinical study to determine the effect of continuation of N2O after dural closure on ICP in patients undergoing craniotomies. Patients were randomly assigned in a 1.5:1 ratio into a group in which N2O was continued after dural closure (N2O, n = 15) or a group in which N2O was discontinued and replaced with nitrogen (N2, n = 9) at the time of dural closure. PaCO2 was normal prior to closure, and end-tidal PCO2 was kept constant after dural closure. Ipsilateral ICP was recorded at 5-min intervals after dural closure until completion of skin closure and immediately postoperatively. Presence of intracranial air was determined by head computed tomography scan within the first postoperative hour. ICP at the time of dural closure did not differ between the groups (N2O: 3 +/- 2 mmHg vs. N2:5 +/- 1 mmHg). Intraoperatively, ICP did not change after dural closure, regardless of whether N2O was continued or discontinued. Postoperatively, ICP was reduced, with a significant decrease in ICP (P less than 0.01) observed only in the N2O group. Postoperative computed tomography scans demonstrated the presence of intracranial air in all patients, with most exhibiting a mild to moderate degree of pneumocephalus. We conclude that continuation of N2O after dural closure did not affect ICP during the craniotomy closure. These results suggest that it is not necessary to discontinue N2O prior to dural closure for reasons of avoiding expansion of intracranial air and increasing ICP. PMID- 1519780 TI - The effect of dobutamine on hepatic blood flow and oxygen supply-uptake ratio during enflurane nitrous oxide anesthesia in humans undergoing liver resection. AB - Liver surgery is often accompanied by hepatic hypoperfusion and hypoxia, and it is controversial whether catecholamines increase hepatic blood flow and oxygen supply. The effects of 3 micrograms.kg-1.min-1 dobutamine on hepatic circulation and oxygen balance were examined in patients anesthetized with enflurane, nitrous oxide, and oxygen for liver surgery. Dobutamine did not cause a significant increase in hepatic arterial blood flow. However, total hepatic blood flow and portal venous blood flow were increased, resulting in an increase in hepatic oxygen delivery (HDO2). The increase in HDO2 was not associated with an improvement of hepatic oxygen supply-uptake ratio, since hepatic oxygen uptake (HVO2) also increased. After hepatectomy, the increases in portal venous blood flow and HDO2 were not accompanied by an increase in HVO2. The stimulation of hepatocellular oxygen metabolism by dobutamine and depressed responsiveness of adrenoceptors on hepatocytes in which metabolism was already augmented are the likely explanation for the different reactions before and after hepatectomy. PMID- 1519781 TI - Preemptive analgesia. Clinical evidence of neuroplasticity contributing to postoperative pain. AB - Recent evidence suggests that surgical incision and other noxious perioperative events may induce prolonged changes in central neural function that later contribute to postoperative pain. The present study tested the hypothesis that patients receiving epidural fentanyl before incision would have less pain and need fewer analgesics post-operatively than patients receiving the same dose of epidural fentanyl after incision. Thirty patients (ASA physical status 2) scheduled for elective thoracic surgery through a posterolateral thoracotomy incision were randomized to one of two groups of equal size and prospectively studied in a double-blind manner. Epidural catheters were placed via the L2-L3 or L3-L4 interspaces preoperatively, and the position was confirmed with lidocaine. Group 1 received epidural fentanyl (4 micrograms/kg, in 20 ml normal saline) before surgical incision, followed by epidural normal saline (20 ml) infused 15 min after incision. Group 2 received epidural normal saline (20 ml) before surgical incision, followed by epidural fentanyl (4 micrograms/kg, in 20 ml normal saline) infused 15 min after incision. No additional analgesics were used before or during the operation. Anesthesia was induced with thiopental (3-5 mg/kg) and maintained with N2O/O2 and isoflurane. Paralysis was achieved with pancuronium (0.1 mg/kg). Postoperative analgesia consisted of patient-controlled intravenous morphine. Visual analogue scale pain scores were significantly less in group 1 (2.6 +/- 0.44) than in group 2 (4.7 +/- 0.58) 6 h after surgery (P less than 0.05), by which time plasma fentanyl concentrations had decreased to subtherapeutic levels (less than 0.15 ng/ml) in both groups.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1519782 TI - The responsiveness of cerebral blood flow to changes in arterial carbon dioxide is maintained during propofol-nitrous oxide anesthesia in humans. AB - Because it is common to manipulate PaCO2 during neurosurgery, it is essential to characterize the relationship between cerebral blood flow (CBF) and changes in PaCO2. The purpose of this study was to investigate the effects of propofol-N2O anesthesia on the CBF response to changes in PaCO2 in healthy subjects. In seven patients, anesthesia was induced with propofol 2.0-2.5 mg/kg and then maintained with a propofol infusion of 12 mg.kg-1.h-1 for 10 min and then 9 mg.kg-1.h-1 for 10 min and then was reduced to 3-6 mg.kg-1.h-1 for the remainder of the study. The subjects' lungs were ventilated with N2O in O2 (FIO2 0.3) to the end-tidal CO2 present before anesthesia, and then CBF was measured using intravenous 133Xe and ten scintillation counters, five over each cerebral hemisphere. ETCO2 then was increased to 50 mmHg and CBF measurement repeated; ETCO2 then was reduced to 30 mmHg and CBF measurement repeated. Concurrent with each CBF measurement, arterial blood was sampled for PaCO2 and hemoglobin measurement. CBF at normocapnia (PaCO2 42 +/- 2 mmHg) was 33 +/- 7 ml.100 g-1.min-1, which increased to 58 +/- 10 ml.100 g-1.min-1 and decreased to 19 +/- 4 ml.100 g-1.min-1 on increasing PaCO2 (53 +/- 4 mmHg) and decreasing PaCO2 (31 +/- 2 mmHg), respectively. Both the PaCO2 and CBF values were statistically different from those measured at any other time (CBF P less than 0.002, PaCO2 P less than 0.001). The slope of CBF versus PaCO2 was 1.56 ml.100 g-1.min-1.mmHg.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1519783 TI - Central effects of epidural and intravenous clonidine in patients anesthetized with enflurane/nitrous oxide. An electroencephalographic analysis. AB - Epidural clonidine produces regional anesthesia as well as sedation and a decrease in anesthetic requirements. To assess these effects, the electroencephalogram (EEG) was recorded after epidural or intravenous (iv) injection of clonidine during enflurane/N2O anesthesia. Eighteen ASA physical status 1 women undergoing vaginal hysterectomy were allocated randomly to receive epidural clonidine (8 micrograms.kg-1 in 4 ml over 2 min) and iv saline (10 ml over 14 min); or epidural saline (4 ml over 2 min) and iv clonidine (8 micrograms.kg-1 in 10 ml over 14 min); or epidural saline (4 ml over 2 min) and iv saline (10 ml over 14 min). The level of anesthesia was kept constant beginning 10 min before and until 44 min after epidural injection. EEG power spectral analysis was performed throughout the study period using a 2-min average of 8-9-s epochs. Clonidine significantly reduced EEG total power only after epidural administration (P less than 0.05). Relative power increased in the delta band in both the epidural and iv clonidine groups (P less than 0.001). The depression of the total EEG power after epidural injection could be explained neither by systemic absorption alone nor by hemodynamic variations. It may represent the contribution of the direct spinal action of this alpha 2-adrenergic agonist to general anesthesia. PMID- 1519784 TI - Transdermal fentanyl for postoperative pain management in patients recovering from abdominal gynecologic surgery. AB - The current placebo-controlled double-blinded study was undertaken to assess the safety and efficacy, as well as the potential clinical role, of the transdermal therapeutic system (TTS) of fentanyl delivery in the postoperative setting. TTS patches releasing 25 micrograms.h-1 or 50 micrograms.h-1 or placebo were applied to 95 women 1 h before abdominal gynecologic surgery during general anesthesia. Postoperatively, patients self-administered intravenous morphine as required using patient-controlled analgesia with a 1-mg incremental dose and a 6-min lockout interval. Each was assessed upon admission to the postanesthesia care unit and at intervals over the following 72 h with respect to vital signs, visual analogue scale pain and satisfaction scores, side effects, and cumulative morphine use. Data were analyzed using analysis of variance, Kruskal-Wallis, and chi-square. P less than 0.05 was considered significant. There were no demographic differences among groups. Beginning 32 h after TTS application, a statistically significant morphine-sparing effect was seen with the 50 micrograms.h-1 patch. There were no significant differences among groups with regard to visual analogue scale pain scores at rest, patient satisfaction, or the incidence of side effects; a significant reduction in pain upon movement was noted at 24 h in patients treated with TTS 50 micrograms.h-1. This finding constituted the only benefit noted with this form of analgesic therapy in the present investigation. PMID- 1519785 TI - Identification of the pharmacogenetic determinants of alfentanil metabolism: cytochrome P-450 3A4. An explanation of the variable elimination clearance. AB - There is considerable variability in the elimination clearance of the opioid analgesic alfentanil. It has been shown previously that alfentanil clearance is independent of the polymorphic debrisoquine hydroxylase (P-450 2D6), and it is therefore of interest to identify the human cytochrome P-450 enzymes involved in noralfentanil formation, the primary reaction involved in the oxidative N dealkylation at the piperidine nitrogen. Purified human P-450 3A4 showed appreciable catalytic activity, and yeast recombinant P-450 3A4 also showed alfentanil oxidation activity. When microsomes prepared from different human liver samples were compared, noralfentanil formation activity was well correlated (r = 0.95,P less than 0.005) with nifedipine oxidation (a P-450 3A4 marker) but not with markers of other P-450s, including phenacetin O-deethylation (P-450 1A2), chlorzoxazone 6-hydroxylation (P-450 2E1), and (S)-mephenytoin 4' hydroxylation (a P-450 2C enzyme). Using antibodies that recognize specific human P-450 enzymes (immunoinhibition techniques), it was possible to demonstrate that anti-P-450 3A4 nearly completely inhibited alfentanil oxidation activity in the human liver microsomes, but no other antibodies showed a measurable inhibitory effect. Selective chemical inhibitors of P-450 3A4, gestodene and troleandomycin, inhibited as much as 90% of the microsomal noralfentanil formation activity, but other chemical inhibitors did not show a detectable inhibitory effect. 7,8 Benzoflavone inhibited as much as 90% of the alfentanil oxidation activity of the microsomal or reconstituted P-450 3A4 system. This work indicates that P-450 3A4 contributes significantly to human liver microsomal alfentanil oxidation, whereas P-450 2D6 does not contribute.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1519786 TI - Prolongation of spinal anesthesia. Differential action of a lipid drug carrier on tetracaine, lidocaine, and procaine. AB - This study evaluates prolongation of spinal anesthesia by incorporating local anesthetics in lipid formulation. The duration and intensity of local anesthetic effect produced by different concentrations of procaine (1%, 2%, 4%), lidocaine (1%, 2%, 4%), or tetracaine (0.5%, 1%, 2%) dissolved in normal saline were compared to those produced by the same concentration of drugs in lipid (iophendylate) solution. Fifty rabbits with chronic indwelling subarachnoid catheters were divided into ten equal groups. Three days after the operation the catheters were injected with aqueous solutions of the anesthetics, and 24 h later each animal received an equivalent dose of the corresponding drug in free-base form dissolved in iophendylate. The duration and intensity of motor blockade were assessed using a modified Bromage scale. A separate group of animals received plain normal saline and, 24 h later, iophendylate alone. The Kruskal-Wallis test followed by the Tukey-type test for nonparametric multiple comparisons and the Mann-Whitney and Friedman tests were used for statistical analysis at P less than 0.05. Normal saline or iophendylate alone did not produce any motor blockade. Our data show that iophendylate preparations of local anesthetics produce prolonged but less intense motor blockade than the aqueous solutions, except for tetracaine 0.5% in iophendylate, which produced shorter duration of motor blockade. The reduced intensity of motor blockade may be explained by decreased availability of local anesthetic at the nerve tissue due to storage of drug in the lipid depot. The increased duration of blockade signifies a sustained release of drug from the depot. PMID- 1519787 TI - Modification of GABA-mediated inhibition by various injectable anesthetics. AB - Increasing doses of the injectable anesthetics etomidate, Saffan, thiopental, ketamine, and xylazine and the vehicles saline and propylene glycol were administered to urethane-anesthetized rats. Their effects in vivo on perforant pathway-evoked field excitatory post-synaptic potentials and population spikes in the hippocampal dentate gyrus were determined. The primary purpose was to ascertain whether these compounds affect hippocampal excitability in a manner consistent with their proposed mechanisms of action. Compared with their respective vehicles, thiopental, etomidate, and xylazine reduced the amplitude of population spikes to single perforant pathway stimulation by 20-30% at the highest doses tested. Xylazine also increased the latency to onset of the population spike. No other effects were observed. Using paired pulse paradigms, it was determined that etomidate produced a dramatic, prolonged reduction in granule cell excitability at interpulse intervals of 10-100 ms. The magnitude of the effect was dose related and was reversible with the discontinuance of administration of the drug. Similar changes occurred with Saffan (althesin) and thiopental. Ketamine produced a small but significant depression in granule cell excitability during intervals of 10-200 ms. Xylazine had no effect. These data corroborate the importance of a prolongation of gamma-aminobutyric acid A mediated inhibition to the mechanism of actions of etomidate, thiopental, and Saffan at relevant exposure concentrations in vivo. PMID- 1519788 TI - Decreased sensitivity to metocurine during long-term phenytoin therapy may be attributable to protein binding and acetylcholine receptor changes. AB - Long-term phenytoin therapy induces resistance to the neuromuscular blocking effects of metocurine. The hypothesis that this is attributable to increased plasma protein binding of the drug (decreased free fraction) related to increased concentrations of alpha 1-acid glycoprotein (AAG) or attributable to the proliferation of acetylcholine receptors (AChR) at the muscle membrane was tested in the rat. After 14 days of phenytoin 40 mg.kg-1, administered intraperitoneally twice daily (n = 12), the neuromuscular pharmacodynamics were evaluated and compared with those of time-matched controls (n = 10). Protein binding was measured by equilibrium dialysis, AAG concentrations by radial immunodiffusion assay, and AChR by 125I-alpha-bungarotoxin binding. The effective dose for 50% inhibition of baseline twitch height (ED50) was significantly greater in the phenytoin group than in the control group (15.03 +/- 1.65 micrograms.kg-1 vs. 9.98 +/- 0.69 micrograms.kg-1, respectively). The concentrations of AAG increased gradually from 133.8 +/- 7.8 micrograms.ml-1 at day 0, to 343.1 +/- 58.0 micrograms.ml-1 at day 7, to 1,729.5 +/- 422.3 micrograms.ml-1 at day 14 in the phenytoin group. The induction of AAG concentrations in plasma was dependent on plasma phenytoin concentrations and was most prominent after 14 days of phenytoin (r = 0.77; P less than 0.01; n = 22). The free fraction of metocurine was significantly decreased in the phenytoin group compared to the control group (67.2 +/- 0.18% vs. 74.5 +/- 2.5%). There was a significant negative correlation between increased AAG concentrations and decreased free fraction (r = 0.65).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1519789 TI - Anesthesia and muscle relaxation with intrathecal injections of AR636 and AG489, two acylpolyamine spider toxins, in rat. AB - Acylpolyamine toxins are constituents isolated from many invertebrate predator venoms. These toxins are structurally novel and potent noncompetitive ligand mediated ion channel antagonists. This study was designed to explore the sensory and motor effects of intrathecally applied acylpolyamine toxin. AR636 and AG489, acylpolyamine toxins from the spiders Argiope aurantia and Agelenopsis aperta, respectively, were injected intrathecally into rats prepared with chronic spinal catheters, and the effect on spinal function was assessed. AR636 was found to evoke a dose-dependent incidence of muscle flaccidity as well as a blockade of the agitation otherwise evoked by noxious mechanical and thermal stimuli applied to the tail or hind paws. AR636 has a calculated effective concentration (EC50) of 2 micrograms for motor inhibition and 7 micrograms for sensory inhibition. In contrast, AG489 was not found to have any effects at the highest tested dose of 50 micrograms. The precise mechanism whereby AR636 exerts its action in the rat spinal cord is not known, but in insect models, this agent is known to act as a postsynaptic, noncompetitive antagonist at a glutamate receptor and to block cholinergic-gated ion channels. Thus, this agent, a representative of the acylpolyamine toxins, has prominent effects on the sensory and motor systems of mammals, and this class of agents may be found to have potential application as spinally acting muscle relaxants and/or anesthetics. PMID- 1519790 TI - Liposome encapsulation prolongs alfentanil spinal analgesia and alters systemic redistribution in the rat. AB - The effect of liposome encapsulation on the analgesia produced by intrathecally administered alfentanil was examined in the rat. In rats prepared with chronic intrathecal catheters, alfentanil in doses of 1-50 micrograms was administered intrathecally in either saline or in multilamellar liposomes (dipalmitoylphosphatidylcholine and cholesterol). Animals were then tested for analgesia by hot-plate and paw-pressure tests. A second group of animals received intrathecal injections of 30 micrograms alfentanil in saline or liposomes, and blood samples were obtained at 5, 15, 45, and 135 min thereafter for measurement of alfentanil plasma concentrations. The liposome preparation markedly prolonged spinal analgesia in the paw-pressure test and to a lesser extent in the hot-plate test. Neither the time to peak analgesia nor the intensity of analgesia differed between the saline and liposome groups. Liposome encapsulation significantly reduced the peak alfentanil plasma concentration at 5 min and prolonged the period in which low but measurable levels of alfentanil could be measured in plasma. These pharmacokinetic data demonstrate that liposome encapsulation resulted in a slow but prolonged appearance of free alfentanil into a diffusible pool available for uptake into the spinal cord. Consistent with the lower peak plasma concentration of alfentanil, the liposome group demonstrated a significantly lower incidence of catalepsy, indicating less systemic redistribution of alfentanil to supraspinal sites. Liposome encapsulation thus appears to produce a significant reduction in peak plasma concentration with a concomitant reduction in systemic side effects and an increase in the duration of action for a given intrathecal dose of the otherwise rapidly cleared alfentanil. PMID- 1519791 TI - Deliberate arterial hypotension does not reduce intraocular pressure in pigs. AB - Among the accepted advantages of general anesthesia in ophthalmic surgery is improved control of intraocular pressure (IOP). Although standard textbooks advocate deliberate arterial hypotension to facilitate intraocular surgery by reducing IOP, scientific proof of such an effect is lacking. The authors investigated effects of induced arterial hypotension on IOP in an anesthetized porcine model. Forty-two piglets were anesthetized with piritramide, were placed in the prone position, and had the anterior chamber of one eye punctured with a small Teflon cannula to measure IOP. Six pigs were used in a pilot study to establish dose-response relationships for the hypotensive agents; 36 pigs were randomly allocated to one of three groups (n = 12) to receive nitroprusside, adenosine, or isoflurane to reduce mean arterial pressure (MAP) by 50%. Measurements were made after initial stabilization of hemodynamic variables and IOP (control), when a stable MAP of 0.5x control was maintained for 10 min or longer, and after return of MAP to a posthypotensive steady state. The median of differences between time intervals was analyzed statistically for all variables. Nitroprusside and adenosine produced hyperdynamic hypotension (cardiac index increased); isoflurane-induced hypotension was hypodynamic. Control IOPs were 12.9, 12.5, and 11.1 mmHg in the nitroprusside, adenosine, and isoflurane groups, respectively. Median change in IOP during hypotension was -1.5, +1.5, and 0 mmHg in the nitroprusside, adenosine, and isoflurane groups, respectively. The IOP during adenosine-induced hypotension was significantly higher than that during either nitroprusside- or isoflurane-induced hypotension. Return of MAP to control levels was frequently associated with intraocular rebound hypertension when arterial hypotension had been induced with adenosine or nitroprusside.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1519792 TI - Effects of sevoflurane and isoflurane on hepatic circulation in the chronically instrumented dog. AB - To compare the effects of sevoflurane and isoflurane on hepatic circulation, eighteen dogs were chronically instrumented for measurements of mean aortic blood pressure and cardiac output and for simultaneous measurements of hepatic and portal blood flows. Each animal was studied while awake and during 1.2 and 2 MAC of either isoflurane or sevoflurane. Both anesthetics induced tachycardia and a dose-dependent decrease in mean aortic blood pressure (isoflurane -27% and -39%; sevoflurane -22% and -37%). Cardiac output decreased only at the highest concentration (isoflurane -10%; sevoflurane -21%). During sevoflurane, portal blood flow decreased at both 1.2 and 2 MAC (-14 and -33%, respectively), whereas an increase in hepatic arterial blood flow was recorded at 2 MAC (+33%). During isoflurane, the only significant change was a decrease in portal blood flow ( 16%) at 1.2 MAC. Neither anesthetic significantly changed renal blood flow. Therefore, both anesthetics led to similar systemic and hepatic vasodilation. PMID- 1519793 TI - The use of computers for controlling the delivery of anesthesia. PMID- 1519794 TI - Cauda equina syndrome following intended epidural anesthesia. PMID- 1519795 TI - Ventilation difficulty secondary to a tracheal diverticulum. PMID- 1519796 TI - Aortic compression by transesophageal echocardiographic probe in infants and children undergoing cardiac surgery. PMID- 1519797 TI - Subdural injection of morphine for analgesia following cesarean section: a report of three cases. PMID- 1519798 TI - Dapsone-induced methemoglobinemia and pulse oximetry. PMID- 1519799 TI - Computerized tomography-guided stellate ganglion blockade. PMID- 1519800 TI - Muscle rigidity following halothane anesthesia in two patients with Freeman Sheldon syndrome. PMID- 1519801 TI - Increased cost of ketorolac versus morphine sulfate. PMID- 1519802 TI - Emergence delirium following oral ketamine. PMID- 1519803 TI - Retrograde wire-guided direct laryngoscopy in a 1-month-old infant. PMID- 1519804 TI - More on: improving the clinical utility of anesthetic drug pharmacokinetics. PMID- 1519805 TI - Evaluation of Tracheal Tube Exchangers for replacement of double-lumen endobronchial tubes. PMID- 1519806 TI - Transesophageal echocardiography in pediatric cardiac surgery. PMID- 1519807 TI - Treatment of complete heart block in a patient with coronary artery disease. PMID- 1519809 TI - Nurses fill niche in corporations. PMID- 1519808 TI - The use of a nasogastric tube as an aid in blind nasotracheal intubation. PMID- 1519810 TI - Clinic provides guidance, education to young mothers. Interview by Robin A Cassetta. PMID- 1519811 TI - AIDS conference slated for October. PMID- 1519812 TI - $14 million cut slated for nursing education in FY 1993. PMID- 1519813 TI - ANA endorses Clinton for president. PMID- 1519814 TI - ANA VP testifies in support of AHCPR. PMID- 1519815 TI - RNs strong at Democratic convention. PMID- 1519816 TI - Avoid interview turn-offs to ensure success. PMID- 1519817 TI - A day in the life of a nurse. School nursing on cutting edge of prevention. PMID- 1519818 TI - ICN to review nursing diagnoses. PMID- 1519819 TI - Nurse researchers show strength on council. PMID- 1519820 TI - Candor used to teach disease prevention. Interview by Victoria McKernan. PMID- 1519821 TI - RN uses community network to combat measles outbreak. Interview by Victoria McKernan. PMID- 1519822 TI - Nurses can help influence decision to quit smoking: cessation has impact on smoker's total health care picture. Interview by Mandy Midulencak. PMID- 1519823 TI - It's time for health care to begin with the individual. As I see it. PMID- 1519824 TI - Tuberculosis: old disease, new problems. PMID- 1519825 TI - Achievement through activism: a call for nurses to be political. PMID- 1519826 TI - FDA releases alert on i.v. needlesticks. PMID- 1519827 TI - RNs pair innovation with immunizations. PMID- 1519828 TI - Greater effect of inhaled budesonide on adenosine 5'-monophosphate-induced than on sodium-metabisulfite-induced bronchoconstriction in asthma. AB - Inhaled glucocorticosteroids (GCS) decrease airway responsiveness (AR) in asthma by mechanisms that may involve suppressing airway inflammation and a reduction in the number of inflammatory cells in the airways. To investigate the functional response to a reduction in airway inflammatory cells in asthma, we studied the effects of inhaled budesonide on AR to three different bronchial challenges, adenosine 5'-monophosphate (AMP), which primarily activates mast cells; methacholine (MCh), a direct stimulus, and sodium metabisulfite (MBS), a neural stimulus. In a double-blind randomized crossover manner, with a washout period of 28 days, 12 subjects with mild asthma underwent inhalation challenge with doubling increments of MCh, MBS, and AMP before and after 14 days of treatment with budesonide 0.8 mg twice daily from a multidose dry-powder delivery system (Turbohaler) or matched placebo. Treatment with budesonide reduced AR to MCh and MBS to a similar degree, displacing the dose-response curve of each agonist to the right by 1.17 (95% confidence intervals, 0.34 to 2.00) and 1.06 (0.34 to 1.78) doubling dilutions, respectively, when compared with placebo (p less than 0.01). Budesonide caused an additional and significantly greater reduction in AR to AMP, displacing the dose-response curve to the right by 2.92 (2.12 to 3.72) doubling dilutions when compared with placebo (p less than 0.001) and to the other challenges (p less than 0.01). We conclude that budesonide reduces AR to MCh and MBS by an action common to the effects of both direct and neural stimuli on airway smooth muscle contraction. The greater reduction in AR to AMP suggests that budesonide may have an additional action by reducing airway mast cell numbers and/or function. PMID- 1519829 TI - Effect of allergen inhalation on the maximal response plateau of the dose response curve to methacholine. AB - Methacholine dose response curves (DRC) in asthmatic subjects are characterized by a leftward shift and increased maximal response. Allergen inhalation in atopic subjects shifts the DRC to the left, but the effect on the shape is unknown. This study was designed to investigate the effect of allergen inhalation on the maximal response plateau of the methacholine DRC in 16 atopic subjects; nine had mild asthma and seven had rhinitis. They were challenged with allergen and with control solutions in a single-blind design. Methacholine challenges (up to 199 mumol) were performed at baseline and 24 h after the control and allergen challenges. A plateau of the DRC was defined as a difference of less than 5% in FEV1 between the last two or more doses. The maximal response was obtained by averaging the values on the plateau and was reached by all except one subject. Allergen inhalation induced an early asthmatic response (EAR) in all subjects and an additional late asthmatic response (LAR) in 6 subjects. In subjects with an EAR alone the maximal response to methacholine 24 h after allergen challenge was not different from control (mean difference, 2.9% fall in FEV1; p greater than 0.05). In subjects with LAR, the mean value for the maximal response increased from 28.5% after control to 36.5% after allergen (mean difference, 8.0%; p less than 0.05). Of six subjects who developed LAR two lost the plateau on the DRC after allergen challenge. We conclude that allergen inhalation increases the maximal response to methacholine in those subjects who have a LAR. PMID- 1519830 TI - Respiratory input impedance from 4 to 256 Hz in normals and chronic airflow obstruction: comparisons and correlations with spirometry. AB - Measurement of respiratory system input impedance (Zrs) by forced oscillation (FO) has generally been limited to frequencies less than or equal to 50 Hz, and correlations with spirometry have been variable. Using FO from 4 to 256 Hz in normals, Jackson and colleagues recently described a first acoustic antiresonance frequency (Far,1) at approximately 170 Hz. Using the same frequency range, we compared several Zrs spectral characteristics with spirometry in 12 chronic airflow obstruction (CAO) patients (range FEV1 0.8 to 2.0 L) and 10 matched controls. Compared with controls, patients had a higher first resonance frequency (Fr,1) (mean +/- SD = 15 +/- 5 versus 10 +/- 2 Hz, p less than 0.02) and a higher Far,1 (196 +/- 11 versus 172 +/- 13 Hz, p less than 0.0002). Good correlations occurred between % predicted FVC and the Far,1 (r = -0.81, p less than 0.0000), between FEV1/FVC and the reactance at 20 Hz (r = -0.6, p less than 0.003), between FEV1 and Far,1 (r = -0.74, p less than 0.0001). Because Far,1 may be affected by airway wall mechanical properties, the shift in Far,1 seen in these patients may be due to airway wall properties in CAO. We conclude that measurement of Zrs up to 256 Hz requires little patient cooperation and may be clinically useful. It can differentiate CAO patients from controls and correlates well with spirometry. The first acoustic antiresonance frequency may reflect airway mechanical properties and provide information not available from Zrs measured at lower frequencies. PMID- 1519831 TI - Changes in cross-sectional airway areas induced by methacholine, histamine, and LTC4 in asthmatic subjects. AB - To examine whether leukotrienes, histamine, and methacholine have different sites of bronchoconstrictor action, we studied 8 stable asthmatic subjects (mean age +/ SD, 26 +/- 5 yr) on 3 different days. On each day, a randomized challenge with LTC4, methacholine, or histamine was performed until the dose that provoked a fall of 20% in FEV1 (PC20) was obtained. Complete and partial flow-volume curves as well as area-distance profiles generated by the acoustic reflection technique (ART) at a fixed lung volume were obtained in all subjects before and after each inhalation challenge. No significant differences were found in pulmonary function or baseline cross-sectional airway areas for the different study days. The three agonists provoked significant (p less than 0.05) bronchoconstriction at the level of the main bronchi when identical falls of FEV1 were achieved. Similarly, equal reductions of V30p were elicited by the three agonists. However, LTC4 and methacholine induced additional tracheal constriction but histamine inhalation did not. These differences in the degree of tracheal constriction were statistically significant (p less than 0.05; ANOVA). These results may be explained by distinct pharmacologic properties of the agents used and may have relevance in the understanding of the pathophysiology of asthma. PMID- 1519832 TI - Upper airway anesthesia induces airflow limitation in awake humans. AB - Upper airway receptors are thought to contribute to upper airway stability by reducing collapsing forces. Their activity can be abolished by topical anesthesia. We have measured in 16 healthy volunteers (mean +/- SD age, 23.7 +/- 1.6 yr) specific airway conductance (SGaw), maximal inspiratory (MIFR) and expiratory (MEFR) flow rates before and 15, 35, and 45 min after extensive upper airway anesthesia (UAA) with 10% lidocaine. Average values of MIFR decreased (p less than 0.01) 15 min after UAA, but they returned to or near to control values at 45 min: MIF25 (4.8 versus 6.0 L/s); MIF50 (5.1 versus 6.2 L/s); MIF75 (4.4 versus 5.3 L/s). Transient decreases in flow (V) rates, reaching zero flow in some subjects, were observed in 13 subjects during forced inspiratory vital capacity (FIVC) maneuvers and in seven subjects during forced expiratory vital capacity (FEVC) maneuvers. MEFR at 25, 50, and 75% FVC, SGaw, and FVC did not change after anesthesia. Simultaneous measurements of supraglottic pressure, V, and lung volume in 12 of the 16 subjects showed that the site of flow limitation was localized at the level of the glottis in all except one subject in whom there was both a glottic and a supraglottic obstruction. We conclude that extensive upper airway anesthesia induced a profound but transitory upper airway obstruction during FIVC and FEVC maneuvers. These findings are compatible with the concept of reflex regulation of upper airway caliber. PMID- 1519833 TI - Decreased airway mucosal prostaglandin E2 production during airway obstruction in an animal model of asthma. AB - Heaves is a respiratory disorder of horses and ponies characterized by bouts of acute airway obstruction and airway hyperresponsiveness. We measured prostaglandin E2 (PGE2) and 15-hydroxyeicosatetraenoic acid (15-HETE) production in vitro in tracheal epithelium obtained from six affected horses at the time of acute airway obstruction as compared with six matched control horses. Strips of epithelium and subepithelial tissue were prepared and stimulated with A23187, histamine, and bradykinin. The PGE2 and 15-HETE in media from strips was quantitated by radioimmunoassay. 15-HETE above the limits of accurate detection was found in epithelial strips of only two principal animals and in none of the control horses, and the amount of 15-HETE was not increased when strips were stimulated. Epithelial strips from affected horses tended to produce less PGE2 than did strips from control horses, and there was a significant correlation between epithelial PGE2 production and the time taken for affected animals to develop airway obstruction. Subepithelial tissue strips from control horses produced significantly more PGE2 in response to A23187 and bradykinin than did strips from affected horses. We conclude that equine tracheal epithelium is not a significant source of 15-HETE. Airway mucosal PGE2 production is reduced in horses with heaves, which suggests that a relative decrease in this bronchorelaxant substance may be a factor in the pathogenesis of this model of asthma. PMID- 1519834 TI - Mucociliary clearance in adult asthma. AB - Severe impairment of mucociliary clearance (MC) in hospitalized asthmatics has recently been demonstrated in peripheral and central airways. MC was also shown to improve with clinical recovery and hospital discharge (2). In the present study, we measure MC in chronic, stable asthma in subjects with a wide range of obstruction to see if MC was related to the severity of chronic disease. We separated the subjects into those with severe obstruction with expiratory flow limitation during tidal breathing (FL subjects) and those without tidal flow limitation (NFL subjects) to see if the presence of chronic flow limitation was associated with regional MC abnormalities. Seventeen asthmatic patients were studied. Mucociliary clearance was assessed using inhaled radioaerosol and serial measurements of the retention of radioactivity over 2 h. By controlling breathing pattern, the initial pattern of deposition in the lungs was matched, with all subjects having a predominance of particles in the central airways. This pattern was normalized for regional lung volume using a xenon equilibrium scan and expressed as a specific central to peripheral (sC/P) ratio. The percentage retention of deposited radioactivity at 120 min ranged from 19 to 83% (mean, 52%). FL subjects had a mean retention at 120 min of 66% (range, 55 to 83%). The NFL subjects had a mean retention at 120 min of 33% (range, 19 to 51%). Throughout the 2-h study period, retention by the FL group was significantly greater than that of the NFL group with separation of 95% confidence intervals.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1519835 TI - Sputum ECP levels correlate with parameters of airflow obstruction. AB - Growing evidence suggests that eosinophils play an important role as proinflammatory cells in asthma, possibly by releasing toxic cationic proteins. In this study concentrations of serum and sputum eosinophil cationic protein (ECP) from 134 patients with productive cough and a history suggestive of airflow obstruction were measured by radioimmunoassay. Small sputum volumes were suspended in saline, vortexed, and centrifuged and ECP measured in the supernatant. Serum ECP levels ranged from 0.002 to 0.095 mg/L (0.016 +/- 0.0014), whereas sputum ECP concentrations were between 0.024 and 5.66 mg/L ECP per g sputum (0.878 +/- 0.092). Only 17 of the 134 patients (14 asthma, one cystic fibrosis, one bronchiectasis, and one bronchitis) had not been pretreated with corticosteroids. Sputum but not serum ECP levels of the 14 patients with asthma were inversely correlated with impairment of FEV1 (r = -0.73). Airway resistance (Raw) (r = 0.71) as well as the change in FEV1 (r = 0.79) and Raw (r = 0.84) after inhalation of 0.2 mg albuterol were positively correlated. This relationship was not observed in the remaining 117 patients on topical and/or systemic corticosteroids, suggesting that corticosteroid treatment influences sputum ECP levels. Also, sputum ECP levels and the degree of sputum eosinophilia were not correlated in any of the patient groups. Neither did serum ECP levels predict sputum ECP concentrations. We conclude that sputum ECP concentrations serve as a marker of eosinophil degranulation in the sputum, and this marker correlates with airflow obstruction. Sputum ECP levels are more closely related to lung function parameters than serum ECP concentrations and/or microscopic sputum analysis. PMID- 1519837 TI - Effect of leukotriene C4 on theophylline disposition in guinea pigs. AB - The pharmacokinetics of theophylline in acutely ill patients show wide intraindividual variability associated with the severity of clinical status. To investigate the mechanism of this variability, we studied the effects of leukotriene C4 (LTC4)-induced pathophysiologic changes on the disposition of theophylline. The plasma concentration-time profiles were measured after simultaneous intravenous bolus injection of theophylline and antipyrine in guinea pigs. The animals received 5 micrograms/kg of LTC4 intravenously 60 min later. The plasma theophylline concentration 30 min after LTC4 treatment was significantly lower (p less than 0.05) than that of nontreated control animals, whereas the plasma antipyrine concentration at that time was not affected. In addition, the treated animals showed significantly slower declines in plasma concentrations of both drugs (0.0805 +/- 0.0199 and 0.291 +/- 0.020 h-1 for theophylline and antipyrine, respectively, mean +/- SEM) than did controls (0.197 +/- 0.010 and 0.439 +/- 0.028 h-1). Leukotriene C4 treatment also induced moderate bronchoconstriction and metabolic acidosis, increased blood hemoglobin concentration and hematocrit, and decreased concentration of serum proteins. In connection with these changes, the plasma unbound fraction of theophylline increased significantly (p less than 0.001, 94.4 +/- 3.3% in treatment versus 58.2 +/- 4.4% in control), but that of antipyrine was unchanged (94.9 +/- 3.0% in treatment versus 92.1 +/- 0.9% in control). These findings indicated that an increase in the volume of distribution was responsible for the abrupt change in plasma theophylline concentration following LTC4 treatment, and the apparent change in the volume of distribution was estimated as 26.1 +/- 5.6%.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1519836 TI - Risk factors for morbidity in mechanically ventilated patients with acute severe asthma. AB - Acute severe asthma is associated with significant morbidity and mortality. We retrospectively quantified hypotension, pulmonary barotrauma, and cardiac arrhythmias in all patients with severe asthma admitted to the intensive care unit (ICU) and prospectively evaluated the predictive value of a measurement of dynamic hyperinflation (DHI) in those patients who required mechanical ventilation. In the first study, 88 ICU admissions for severe asthma over 5 yr (73 patients, 40 +/- 18 yr, 36 men, 37 women) were evaluated. Fifty-one admissions were mechanically ventilated, 29 were not, and 8 previously ventilated patients remained briefly intubated but were not ventilated in the ICU. Hypotension (18/88, 20%), pulmonary barotrauma (12/88, 14%), and arrhythmias (9/88, 10%) were entirely confined to patients who had been mechanically ventilated. There were no significant differences in ventilatory parameters, airway pressures, or blood gases between mechanically ventilated patients with and without complications. Two patients with previous severe hypoxic cerebral damage died from this complication after ICU discharge. In the second study, the end-inspiratory lung volume (VEI) (1) was compared with standard ventilatory parameters in 22 patients. There were no ICU deaths, but high incidences of pulmonary barotrauma (27%) and hypotension (41%) were found. Both minute ventilation (VE and VEI) were significantly higher in patients who developed complications (VE 13.7 +/- 3.0 versus 11.2 +/- 2.5 L/min, VEI 26.1 +/- 4.7 versus 20.0 +/- 7.4 ml/kg, p less than 0.05) but only VEI had a threshold value significantly predictive of complications. For VEI less than 1.4 L, 0/5 (0%) patients had complications; for VEI greater than or equal to 1.4 L, 11/17 (65%) had complications (p = 0.03).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1519838 TI - Sulfuric acid aerosol exposure in humans assessed by bronchoalveolar lavage. AB - Epidemiologic and experimental evidence suggests that exposure to acidic aerosols may affect human health. Brief exposures to acidic aerosols alter mucociliary clearance and increase airway responsiveness, but effects on host defense mechanisms at the alveolar level have not been studied in humans. Twelve healthy, nonsmoking volunteers between 20 and 39 yr of age were exposed for 2 h to aerosols of approximately 1,000 micrograms/m3 sulfuric acid (H2SO4) or sodium chloride (NaCl [control]), with intermittent exercise, in a randomized, double blind fashion. Each subject received both exposures, separated by at least 2 wk. Bronchoalveolar lavage (BAL) was performed 18 h after exposure in order to detect evidence of an inflammatory response, changes in alveolar cell subpopulations, or changes in alveolar macrophage (AM) function, which is important in host defense. When compared with NaCl, exposure to H2SO4 did not increase polymorphonuclear leukocytes in BAL fluid. The percentage of T lymphocytes decreased in association with H2SO4 exposure, but the difference was not statistically significant (14.9% after NaCl, 11.5% after H2SO4; p = 0.14). Antibody-mediated cytotoxicity of AM increased in association with H2SO4 exposure (percent lysis 19.1 after NaCl, 23.6 after H2SO4; p = 0.16). No significant change was seen in release of superoxide anion or inactivation of influenza virus in vitro. Brief exposures to H2SO4 aerosol at 1,000 micrograms/m3 do not cause an influx of inflammatory cells into the alveolar space, and no evidence was found for alteration in antimicrobial defense 18 h after exposure. PMID- 1519839 TI - Toward a definition of asthma for epidemiology. AB - Because there is no "gold standard" for defining asthma for epidemiology, we have defined current asthma as bronchial hyperresponsiveness (BHR) plus recent wheeze (in the 12 months prior to study). To describe the characteristics of groups categorized by these measurements, we studied two samples of children aged 7 to 12 yr: 210 from a population sample and 142 self-identified asthmatics. Bronchial responsiveness to histamine was measured by the rapid method, respiratory symptom history, and asthma medication use by self-administered questionnaire to parents and atopy by skin prick tests to 14 allergens. Children recorded daily Airflometer readings and symptom scores for 2 wk. Children with current asthma had more severe bronchial responsiveness, greater Airflometer variability, more symptoms, more atopy (particularly to house dust mites), and used more asthma medication than children with BHR or recent wheeze alone. Children with BHR, but not with recent wheeze, were intermediate between the current asthma and normal groups in terms of bronchial responsiveness, Airflometer variability, and atopy. Children with recent wheeze and normal responsiveness differed from the normal group only in symptoms and medication use. Our definition of current asthma discriminates a group of children that is clearly different in terms of both clinical features and physiologic measures. As such, it is the most useful definition to date for measuring the prevalence of clinically important asthma in populations. PMID- 1519840 TI - Relationship of skin test reactivity and eosinophilia to level of pulmonary function in a community-based population study. AB - We studied the relationship of skin test reactivity (sumscore greater than or equal to 3) and eosinophilia (greater than or equal to 275 cells/mm3 blood), separately and combined, to the level of FEV1 in a community cohort. We used the regression analysis technique, adjusting for age and area of residence, and stratifying by gender and cigarette smoking. Eosinophilia, among men, was associated with lower levels of FEV1 in skin test negative subjects with moderate cigarette smoking (greater than or equal to 10 pack-yr: beta = -250 ml, p = 0.02; greater than or equal to 10 pack-yr: beta = -234 ml, p less than 0.01) and in skin test positive subjects who either never smoked (beta = -228 ml, p = 0.06) or had only a brief history of smoking (beta = -428 ml, p less than 0.01). Eosinophilia, among women, was significantly associated with lower levels of FEV1 in never smokers (beta = -95 ml, p less than 0.01), especially if subjects were skin test positive as well (beta = -289 ml, p less than 0.01). Moderate cigarette smoking was uncommon in women. These data suggest an association of indices of inflammation (eosinophilia alone) and allergic inflammation (eosinophilia combined with skin test reactivity) with lower levels of FEV1, independent of the effect of cigarette smoking. PMID- 1519842 TI - Silo filler's disease in New York State. AB - Twenty new cases of Silo filler's disease (SFD) have been collected, documenting the incidence and clinical features of exposure to nitrogen oxides present in freshly filled silos. Cases of SFD were identified using a statewide computerized discharge diagnosis system. Fifteen of these were identified in the index period, allowing us to calculate an approximate annual incidence of 5.0 cases/100,000 silo-associated farm workers/yr in New York State. All cases occurred during harvest periods, with 80% in September and October. Corn silage was the gas source in 18 (90%). All cases involved young white men (mean age, 31.5 yr). The most common presenting feature was dyspnea. All victims entered a silo during the peak danger period, and only one used recommended ventilation techniques. Four cases ended in death (20% mortality). Silo filler's disease, although rare, is a potentially devastating disease involving otherwise young, healthy farm workers. It is readily prevented. PMID- 1519841 TI - Are race and sex differences in lung function explained by frame size? The CARDIA Study. AB - Using the CARDIA cohort of 20- to 32-yr-old black and white men and women, FVC and FEV1 were standardized for standing height, sitting height, leg height, elbow breadth, and biacromial diameter in such a way that the standardized lung function showed minimal statistical dependence on these measures of frame size. Race and sex differences in lung function have been reported even after adjustment for height; however, these differences might depend on aspects of frame size other than height. We found that within this age group height2 provided robust standardization for FVC and FEV1 for all race and sex strata of the population. Height explained approximately 40% of the variance of FVC and FEV1 in whites, 30% in black women, and 20% in black men. In black men only, standardization for the combination of sitting height, leg height, elbow breadth, and biacromial diameter improved explained variance to nearly 40% for FVC and nearly 30% for FEV1. After standardization for height, FVC and FEV1 were found to be 14 to 19% higher in whites than in blacks, and in men than in women. Standardization of FVC and FEV1 for sitting height, leg height, elbow breadth, and biacromial diameter combined reduced these differences to 13-16%. Thus, race and sex differences in lung function exist even after detailed adjustment for frame size. PMID- 1519843 TI - Delayed effects of NO2 exposure on alveolar permeability and glutathione peroxidase in healthy humans. AB - Potential toxic effects of prolonged NO2 exposure below the current threshold limit value (TLV) were examined in 14 healthy, nonsmoking adults. The subjects were exposed to 2.3 ppm NO2 and to clean air for 5 h with a 1-wk interval between exposures. Physiologic and biochemical measurements were obtained during the exposures and until 24 h after. A 14% decrease in serum glutathione peroxidase activity (GSH-Px) was observed 24 h after the start of the NO2 exposure, while indications of a 22% decrease in alveolar permeability were found 11 h after the start. There were no indications of mucous membrane irritation or of decreased lung function during or after NO2 exposures. The results support the assumption that a delayed response is a feature of the human reaction to NO2 even below the current TLV of 3 ppm, and they stress the importance of an extended period of observation in future NO2 exposure studies. PMID- 1519844 TI - Corticosteroid administration modifies ozone-induced increases in sheep airway blood flow. AB - Recently, we have shown that exposure of intubated conscious sheep to 3 to 4 ppm ozone (O3) for 3 h increases bronchial blood flow (Qbr). The purpose of the present study was to assess the potential role of corticosteroids in modulating this increase. Six nasally intubated sheep were exposed to filtered room air, 3.5 ppm O3 on two separate occasions, and 3.5 ppm O3 plus methyl-prednisone, for 3 h. Qbr was measured using a chronically implanted 20 MHz pulsed Doppler flow probe. Qbr, mean aortic pressure, cardiac output, pulmonary artery pressure, arterial blood gases, and core temperature were monitored. After 3 h of 3.5 ppm O3, Qbr increased from 3.2 +/- 0.5 (mean +/- SEM) to 8.5 +/- 1.6 KHz, whereas bronchial vascular resistance (BVR) decreased from the baseline value of 43.6 +/- 8.0 to 15.0 +/- 3 mm Hg/KHz. With corticosteroids, baseline Qbr was 3.2 +/- 0.6 and BVR was 44.2 +/- 9.7; after 3 h of 3.5 ppm O3, Qbr was 3.3 +/- 0.5 KHz and BVR was 39.0 +/- 8.0 mm Hg/KHz. The two 3.5-ppm O3 exposures without corticosteroids were impressively reproducible. Except for Qbr and BVR, no other measured cardiovascular parameters were affected by O3. The results indicate that corticosteroids are capable of interfering with mediator, neurohumoral, or inflammatory cell mechanisms responsible for vasodilation of the airway microcirculation after O3 exposure, but do not specifically address the specific processes whereby this attenuation occurs. PMID- 1519845 TI - Acute effect of oxygen on pulmonary arterial pressure does not predict survival on long-term oxygen therapy in patients with chronic obstructive pulmonary disease. AB - The growing number of patients treated with long-term oxygen therapy (LTOT) poses the question which physiologic variables could predict the patients who may benefit the most from this cumbersome and expensive treatment. We wanted to verify if the acute effect of oxygen on pulmonary arterial pressure (PAP) is related to survival on LTOT as was suggested recently in the literature. We studied 46 chronic obstructive pulmonary disease (COPD) patients qualified for LTOT. The acute effects of O2 on pulmonary hemodynamics were assessed by pressure and flow measurements before and after 30 min of O2 breathing via 28% Ventimask. Thirty-nine patients reacted with a fall of the mean PAP of less than 0.7 kPa 5 (mm Hg). These were termed nonresponders (NR). In seven patients, mean PAP fell greater than or equal to 0.7 kPa 5 (mm Hg). They were called responders (R). After the initial investigations, patients were followed up on LTOT for 2 yr or until death. During the first year, four patients died; three from the NR and one from the R group. After 2 yr of LTOT, 15 patients died (12 from NR and 3 from R groups). The 2-yr survival rate was 69% in NR and 57% in R groups, respectively. We conclude that survival on LTOT is not related to the acute effect of oxygen on the PAP in COPD patients investigated in the steady-state period of the disease. PMID- 1519847 TI - Hemodynamic differences between continual positive and two types of negative pressure ventilation. AB - In seven anesthetized dogs, ventilated with matching lung volumes, tidal volumes, and respiratory rates, we compared the effects on cardiac output (CO), arterial venous oxygen saturation difference (SaO2 - SVO2), and femoral and inferior vena cava pressure (1) intermittent positive pressure ventilation with positive end expiratory pressure (CPPV); (2) iron-lung ventilation with negative end expiratory pressure (ILV-NEEP); (3) grid and wrap ventilation with NEEP applied to the thorax and upper abdomen (G&W-NEEP). The values of CO and SaO2 - SVO2 with ILV-NEEP were similar to those with CPPV. However, with G&W-NEEP as compared with ILV-NEEP, mean CO was greater (2.9 versus 2.6 L/min, p = 0.02) and mean (SaO2 - SVO2) was lower (26.6% versus 28.3%, p = NS). Mean PFEM-IVC was higher with G&W NEEP than with the other types of ventilation. We conclude that (1) ILV-NEEP is hemodynamically equivalent to CPPV and (2) G&W-NEEP has less adverse hemodynamic consequences. has less adverse hemodynamic consequences. PMID- 1519846 TI - Adenosine is a pulmonary vasodilator in newborn lambs. AB - We investigated the systemic and pulmonary vascular effects of adenosine and determined plasma adenosine levels in pulmonary circulation in 12 newborn lambs during normoxia and during alveolar hypoxia (10% O2, 5% CO2, and 85% N2). Lambs were instrumented at 7 days of age with catheters in the descending aorta, main pulmonary artery, and right and left atria, and a flow transducer around the main pulmonary artery, and were studied following a 3-day recovery. Adenosine or an equal volume of normal saline (control) was infused into the right atrial line in doses ranging from 0.01 to 2.5 mumol/kg/min. In normoxic lambs, adenosine caused a significant decrease in pulmonary vascular resistance and increase in heart rate in doses of 0.15 to 2.5 mumol/kg/min and a decrease in systemic vascular resistance, with increase in cardiac output in doses of 0.3 to 2.5 mumol/kg/min. Baseline plasma adenosine levels in pulmonary artery and left atrium decreased significantly during alveolar hypoxia. Adenosine infusion in hypoxic lambs caused decreases in pulmonary artery pressure and pulmonary vascular resistance at all the doses tested. Aortic pressure and systemic vascular resistance decreased, and heart rate and cardiac output increased at doses greater than or equal to 0.3 mumol/kg/min in hypoxic lambs during adenosine infusion. The pulmonary vascular effects of adenosine in hypoxic lambs were attenuated by prior treatment of animals with aminophylline. Thus, adenosine appears to be an important regulator of pulmonary vascular response to hypoxia in newborn lambs. Its vasodilator effects were specific for pulmonary circulation when it was infused in doses less than or equal to 0.15 mumol/kg/min into the right atrium and appear to be mediated by P1 purinergic receptors. PMID- 1519848 TI - Effect of positive end-expiratory pressure on right ventricular function in humans. AB - The effect of positive end-expiratory pressure (PEEP) on right ventricular (RV) function in humans is complex. Previous studies have been limited in their interpretation by not defining either pericardial pressure (Ppc) or RV volumes. Accordingly, we measured RV volumes and pressures and Ppc as PEEP was increased from zero to 15 cm H2O in 12 patients after thoracotomy, using a pulmonary arterial catheter equipped with a rapid responding thermistor that allowed measurement of RV ejection fraction (ef), while Ppc was measured via a pericardial balloon catheter. RV end-diastolic volume (EDV) was estimated as the ratio of stroke volume (SV) to RVef, whereas RV end-systolic volume (ESV) was estimated as RV EDV-SV. Right atrial pressure (Pra) was defined as end-diastolic pressure, and pulmonary arterial pressures (Ppa), both peak and mean, were used as end-systolic pressures. PEEP increased Ppc, Pra, and lung compliance (Cl). Cardiac output also decreased but not significantly. Neither mean nor peak systolic Ppa, nor RVef was significantly altered by PEEP. There was no relation between either RV filling pressure (Pra-Ppc) and EDV or the change in RV filling pressure and EDV, although EDV varied significantly as PEEP varied for individuals (p less than 0.05). Similarly, there was no relation between Ppa and ESV when either mean or peak Ppa values relative to Ppc were used. The relations between EDV and both SV and RVef were weak (r = 0.54 and 0.55, respectively). RVef varied inversely with ESV (r = -0.77), although it showed no relation to transmural peak Ppa (r = 0.28).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1519849 TI - Adaptations of the peripheral circulation to PEEP. AB - The purpose of this study was to determine the role of changes in the parameters of venous return on the homeostatic adaption to the application of PEEP. We studied 13 dogs anesthetized with alpha-chloralose, intubated, and ventilated. We measured central venous pressure (CVP), arterial pressure (Pao) and cardiac output by thermal dilution. The cardiac output was transiently stopped by inflating a balloon in the right atrium, and the subsequent plateau in the CVP was used to obtain mean circulatory filling pressure (MCFP). Total blood volume was measured with Evans blue. To measure vascular capacitance and compliance, we rapidly infused 4 ml/kg or 8 ml/kg of blood and repeated the MCFP measurement. The same volume was withdrawn after the measurement. The volume and MCFP were used to construct pressure-volume (P-V) lines, and the unstressed volume was calculated by extrapolating the P-V to zero pressure. The P-V appeared linear in the range studied. PEEP produced a left shift of the curves and, thus, a decrease in unstressed volume. The shift with 20 cm H2O of PEEP was greater than with 10 cm H2O of PEEP. The rise in MCFP matched the rise in CVP so that the pressure gradient for venous return did not change. However, there was also an increase in the resistance to venous return, which resulted in a lower cardiac output than expected for the rise in MCFP. In conclusion, homeostatic adjustments to PEEP included a decrease in vascular capacitance, which is partially offset by a rise in the resistance to venous return. PMID- 1519850 TI - Studies on the role of tumor necrosis factor in adult respiratory distress syndrome. AB - Tumor necrosis factor (TNF), rapidly becoming recognized as a mediator of inflammation, may be important in the pathogenesis of acute lung injury. Its role in the development of the adult respiratory distress syndrome (ARDS) in humans, however, has been difficult to clarify. To determine if TNF could be important early in the development of acute lung injury from multiple causes, we enrolled 103 patients within 8 h of meeting the criteria for an at-risk illness (sepsis, aspiration of gastric contents, severe pancreatitis, hypertransfusion, abdominal trauma, chest trauma, multiple fractures) and obtained multiple frequent blood samples for TNF measurements. Using five methods of TNF analysis, we were unable to find an association between TNF and the development of ARDS. However, we found significant differences in TNF measurements depending on the methods of analysis used, which could, at least in part, account for the inconsistencies in the published literature regarding the relationship between TNF and disease processes. PMID- 1519851 TI - Serum and bronchoalveolar lavage of N-terminal type III procollagen peptides in idiopathic pulmonary fibrosis. AB - Collagen deposition is a prime determinant of clinical course in idiopathic pulmonary fibrosis (IPF). Identification of a marker of connective tissue metabolism would significantly enhance the ability to stage the disease and monitor the course of these patients. Prior studies of IPF have indicated that N terminal Type III procollagen peptide (N-PIIIP) levels in blood and bronchoalveolar lavage BAL fluid are elevated. We hypothesized that elevated levels of procollagen peptides are a marker of enhanced collagen deposition, which is associated with interstitial fibrosis characterizing active disease. The purpose of the present study was to explore the relationship between N-PIIIP recovery and physiologic parameters of lung function. N-PIIIP levels in sera and bronchoalveolar lavage (BAL) from 24 patients with IPF and 29 volunteers were measured by radioimmunoassay. The extent of disease in IPF was assessed by clinical history, physical examination, chest radiograph, pulmonary physiology evaluation, and confirmatory open-lung biopsy. The severity of disease was graded using a previously described clinical, radiologic, and physiologic (CRP) scoring system. N-PIIIP normalized to albumin was higher in BAL than in serum for both volunteers (1.6-fold; p less than 0.05) and IPF patients (24-fold; p less than 0.05), consistent with local pulmonary production. BAL N-PIIIP was significantly elevated in IPF patients, whether expressed as concentration (healthy volunteer 0.11 +/- 0.06 ng/ml; IPF, 5.0 +/- 14.4; mean +/- SD; p less than 0.05) or normalized to albumin (healthy volunteer, 2.8 +/- 1.2; IPF, 73 +/- 106; p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1519852 TI - Amelioration of sleep apnea by salicylate-induced hyperventilation. AB - It is well documented that upper airway (UAW) muscle activity is augmented in response to increased respiratory drive, the overall effect being an improvement in UAW patency. We have recently shown that salicylate-induced ventilatory stimulation increased UAW muscle electrical activity and decreased UAW resistance and collapsibility in anesthetized dogs. In the present study, we evaluated the effect of respiratory stimulation produced by high therapeutic doses of aspirin on sleep in nine patients with previously diagnosed sleep apnea. A control, all night, polysomnographic sleep study, including oximetry and ventilatory monitoring by inductive plethysmography, was compared with a second study undertaken after patients ingested 8 to 10 g of aspirin over a period of 4 to 5 h. Aspirin ingestion resulted in high therapeutic salicylate serum levels (33 +/- 2.5 mg/dl, mean +/- SE) the following morning and was associated with marked ventilatory stimulation. Mean sleep duration and the relative partitioning of sleep stages were not affected by aspirin. However, aspirin-induced hyperventilation was associated with a significant non-rapid decrease in periodic breathing and the frequency of both obstructive and mixed apneas in all non-rapid eye movement (REM) sleep stages. The total number of apneas over the whole night was reduced in all subjects and on average fell from a control rate of 42 +/- 7 to 28 +/- 7 apneas/h (p less than 0.01). Similarly, the mean duration of apneas fell from 23 +/- 2 to 20 +/- 1 s (p less than 0.05), and the overall time spent in apneas decreased from 17 +/- 3 to 10 +/- 3 min/h (p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1519853 TI - Effect of negative pressure ventilation on ventilatory muscle endurance in patients with severe chronic obstructive pulmonary disease. AB - We studied five men with chronic obstructive pulmonary disease (COPD) (mean age, 65 +/- SEM 2 yr; FEV1, 0.68 +/- 0.08 L; and FEV1/FVC, 38 +/- 2%) to determine the relationship between ventilatory muscle endurance (VME) and ventilatory muscle rest (VMR) elicited by negative-pressure ventilation (NPV). VME was measured as the maximal sustainable ventilation (MSVC) that the subjects could maintain for 12 min. Prior to therapy, MSVC for the subjects was 25.0 +/- 3.6 L/min. During the therapy phase, subjects received 4 wk of daily "in-hospital-supervised" NPV therapy (4 h/day). While subjects received therapy, we quantified VMR by (1) the percentage of breaths that were "in synchrony" and by (2) the percentage of breaths showing "turn-off" of the diaphragmatic EMG signal (EMGdl). During the therapy sessions, 93 +/- 2% of breaths were in synchrony, whereas 66 +/- 11% showed EMGdl turn-off. During post-therapy testing, an increase in MSVC was noted in each of the subjects; the mean increase was 4.0 +/- 1.3 L/min (p less than 0.05), which represented an increase of 16 +/- 4% over pretherapy values. Increases in MSVC were highly correlated with both the percentage of in-synchrony breaths (r = 0.96, p less than 0.01) and the percentage of breaths showing EMGdl turn-off (r = 0.92, p less than 0.02). However, NPV therapy elicited no other improvements in either clinical or laboratory measurements. Moreover, patients exhibited marked dyspnea with initiation and termination of daily NPV therapy.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1519854 TI - Effects of N-acetylcysteine on diaphragmatic function and malondialdehyde content in Escherichia coli endotoxemic rats. AB - We evaluated the effects of sublethal Escherichia coli endotoxemia with or without concomitant administration of N-acetylcysteine, an antioxidant agent, on diaphragmatic strength, endurance, and malondialdehyde (MDA) content in rats. One hundred ninety rats were inoculated subcutaneously on 2 successive days with 0.6 and 1.2 mg/100 g body weight of E. coli lipopolysaccharide respectively (E animals, n = 100) or saline (C group, n = 90). E and C animals were divided into two groups based on administration of endotoxin or saline alone (E group, n = 55; C group, n = 47, respectively) or endotoxin or saline plus N-acetylcysteine (1 g/kg body weight/day intraperitoneally) (E-NAC group, n = 45; C-NAC group, n = 43, respectively). Diaphragmatic strength was assessed in vivo 48 h after the first endotoxin or saline administration by measuring the transdiaphragmatic pressure (Pdl) generated during electrical stimulation of the phrenic nerves at 0.5, 10, 20, 30, 50, and 100 Hz. Endurance index was calculated as the percent ratio of Pdl generated after 30 s of phrenic stimulation at 10 Hz divided by the initial force. Diaphragmatic MDA (fluorometric technique) was measured 0, 6, 18, 30, 42, and 48 h after the first dose of endotoxin or saline. Pdl for 50 and 100 Hz was significantly reduced in Group E as compared with group C. This phenomenon was associated with a reduced endurance performance as assessed by a lower diaphragmatic endurance index in E as compared with C animals (90.9 +/- 4.2 versus 114.3 +/- 4.1 respectively; p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1519855 TI - Influence of Pneumocystis carinii pneumonia on serum and tissue concentrations of pentamidine administered to rats by tracheal injections. AB - Pentamidine isethionate was administered by the tracheal route to control rats and immunodepressed rats with Pneumocystis carinii pneumonia (PCP). The serum concentration of pentamidine base 20 min after the administration was higher in the PCP rats (309 +/- 165 ng/ml) than in the control animals (71 +/- 36 mg/ml; p less than 0.001); 90 min after the injection the proportion of the pentamidine administered was lower in the right lung of the PCP rats (29 +/- 15%) than in the control rats (57 +/- 23%; p = 0.038); the proportion of pentamidine in the left kidney was higher in the PCP rats (14 +/- 4%) than in the control animals (4 +/- 2%; p less than 0.001). Respiratory clearance of 99mTc-DTPA, an index of the permeability of the respiratory epithelium, was higher in the PCP rats (1.84 +/- 0.42 %/min) than in the controls (0.44 +/- 0.11 %/min; p less than 0.001). We conclude that the more rapid diffusion of pentamidine from the alveolar lumen to the pulmonary circulation is explained by the increased alveolocapillary permeability as a result of pneumocystosis. PMID- 1519856 TI - Higher pentamidine levels in AIDS patients with hypoglycemia and azotemia during treatment of Pneumocystis carinii pneumonia. AB - Trimethoprim-sulfamethoxazole (TMP-SMZ) and pentamidine are both licensed for the treatment of Pneumocystis carinii pneumonia (PCP). However, their use is associated with various adverse side effects. In this prospective study, 26 AIDS patients with 32 episodes of PCP were treated with pentamidine (4 mg/kg/d). Each patient was treated for 12 to 21 days, depending on the rapidity of onset of the clinical response. During the 32 PCP episodes, hypoglycemia occurred in 16 instances, azotemia in 12, liver toxicity in 10, and leukopenia in 8. The occurrence of thrombopenia, leukopenia, and liver toxicity was not related to age, pentamidine levels, or other complications. However, patients who had hypoglycemia during pentamidine treatment had higher serum pentamidine levels than patients who did not have hypoglycemia (107 +/- 40 versus 70 +/- 26 ng/ml, p less than 0.004). In addition, we observed that patients with azotemia showed higher pentamidine levels during treatment (120 +/- 35 versus 64 +/- 22 ng/ml, p less than 0.001). In fact, 100% (11/11) of patients with serum pentamidine concentration greater than 100 ng/ml had fasting hypoglycemia and/or azotemia, while 33% (7/21) of those with pentamidine levels less than 100 ng/ml had these side effects (p less than 0.001). The relative risk of these complications with pentamidine levels greater than 100 ng/ml was 3 (95% confidence interval, 1.6 to 5.5). Fine-tuning the dose of pentamidine may eventually prove useful to avoid toxicity and optimize therapy. PMID- 1519857 TI - Pulmonary function in human immunodeficiency virus infection. A prospective 18 month study of serial lung function in 474 patients. AB - To investigate the development of a reduced DLCO in patients with HIV-related disease, we studied 474 HIV-seropositive patients and performed serial lung function measurements over 18 months. The mean values of DLCO at presentation were lower in patients with more advanced HIV disease compared with asymptomatic HIV-seropositive patients (DLCO 88% of predicted). When compared with the DLCO in asymptomatic HIV-seropositive patients, the DLCO had reduced values in patients with persistent generalized lymphadenopathy (PGL) (82% of predicted, p less than 0.05), acquired deficiency syndrome-related complex (ARC) (73% predicted, p less than 0.001), nonpulmonary Kaposi's sarcoma (KS) (72% of predicted, p less than 0.001), nonpulmonary complications of AIDS excluding KS (73% of predicted, p less than 0.001), pulmonary KS (63% of predicted, p less than 0.001), pulmonary mycobacterial infection (68% of predicted, p less than 0.05), pyogenic infection (70%, p less than 0.05), acute Pneumocystis carinii pneumonia (PCP; 49%, p less than 0.001), and following recovery from PCP (71%, p less than 0.001). Serial lung function measurements over 18 months revealed no change in DLCO within any patient group, and in particular there was no tendency for a gradual decline. Clinical deterioration due to the development of PCP was associated with a reduction in DLCO. Conversely, in patients recovering from PCP, there was a partial improvement in DLCO over 3 months. Zidovudine (AZT) use did not affect DLCO within any diagnostic group or the recovery in DLCO following PCP. However, cigarette smoking was associated with further reductions in DLCO in all patient groups and with an impaired recovery of DLCO following acute PCP.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1519858 TI - Factors associated with tuberculin reactivity among the foreign-born in Montreal. AB - Because tuberculosis among the foreign-born is of increasing importance in North America, it has recently been recommended that newly arriving immigrants be tuberculin tested and preventive therapy given to all those with significant reactions. The factors affecting the prevalence of tuberculin reactions were assessed in a community-based tuberculin survey among foreign-born schoolchildren and young adults. Of 1,198 foreign-born who were tuberculin tested, 32.4% had significant tuberculin reactions. False-positive tuberculin reactions due to sensitivity to purified protein derivative (PPD)-B (for Mycobacterium avium) were uncommon and those due to BCG vaccination of importance only among immigrants from countries with low tuberculosis rates. Tuberculin reactions of 10+ mm were associated with tuberculosis rates in the country of origin (p less than or equal to 0.001), age when immigrated (p less than or equal to 0.001), bacillus Calmette Guerin (BCG) vaccination (p less than or equal to 0.01), and residence in poorer neighborhoods in Montreal (p less than or equal to 0.001), but not with number of years resident in Canada. The booster phenomenon, seen in 16% of those undergoing two-step testing, was most strongly associated with prior BCG vaccination (p less than or equal to 0.001) and also with tuberculosis rates in the country of origin (p less than or equal to 0.08), age of immigration (p less than or equal to 0.01), and number of years resident in Canada (p less than or equal to 0.05).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1519859 TI - Ultrasonographic evaluation of pulmonary consolidation. AB - A total of 161 patients with lobar or segmental consolidation were examined by realtime ultrasound and Doppler ultrasound. Air bronchograms were detected in 141 patients, fluid bronchograms in 27 patients, and parapneumonic effusion in 74 patients. In 36 patients with necrotizing pneumonia, ultrasound detected microabscesses in 33 (91.7%) compared with the air-fluid levels detected by standard chest radiographs in 20 patients (55.6%; p less than 0.05). Of 31 patients with tumors causing obstructive pneumonitis, 29 (93.5%) had tumors detected by chest ultrasound, whereas only 11 patients (35.5%) had chest radiographs that suggested a tumor was causing the obstructive pneumonitis (p less than 0.05). Chest ultrasound was used to guide thoracentesis for parapneumonic effusion in 65 patients, with a 100% success rate. Twenty-six patients with necrotizing pneumonia underwent ultrasound-guided needle aspiration of microabscesses. The procedure was successful in 24 patients (92.3%), and 21 patients (80.8%) had microbiologic confirmation. Twenty patients with tumor associated obstructive pneumonitis received needle aspiration biopsy under ultrasound guidance; 19 patients (95.0%) had the histology confirmed. Five patients with malignancy manifesting as pulmonary consolidation underwent a diagnostic ultrasound-guided needle aspiration biopsy. Five patients (3.8%) developed complications of minimal pneumothorax or mild hemoptysis in 132 episodes of needle aspiration. We conclude that ultrasonography is useful for the evaluation of pulmonary consolidation. It can also be used for needle aspiration guidance for etiologic diagnosis of patients with complicated pneumonia. PMID- 1519860 TI - Ultrasound-guided core biopsy of thoracic tumors. AB - Two hundred and eighteen patients, with thoracic tumors larger than 3 cm in size, underwent ultrasound-guided percutaneous transthoracic core biopsy with a large bore Tru-Cut needle. Fifty-five tumors were in the mediastinum, and 122 tumors were located at subpleural area, and 42 tumors were within the lungs. In 122 subpleural tumors, the sensitivity of ultrasound-guided core biopsy for the diagnosis of malignancy was 96.8%, and accuracy was 97.5%. Sensitivity for the diagnosis of malignant tumors located within the lungs was 94.6%, and accuracy was 95.2%. In 54 patients with mediastinal tumors, definite histologic diagnosis could be obtained in 48 patients (88.9%). The sensitivity of ultrasound-guided biopsy for the diagnosis of malignancy in these 48 mediastinal tumors was 97.1%, with an accuracy of 97.9%. Three patients had complications with minimal pneumothorax and one with mild hemoptysis. We conclude that percutaneous transthoracic core biopsy with Tru-Cut needle under ultrasound guidance is a safe and sensitive way to obtain specimens for accurate histologic diagnosis of thoracic tumors. The diagnostic yield is high, and the technique, relatively simple, can also be used for outpatients. PMID- 1519861 TI - Tumor necrosis factor alpha and interleukin-6 production by human mononuclear phagocytes from allergic asthmatics after IgE-dependent stimulation. AB - We have previously demonstrated the production of tumor necrosis factor alpha (TNF) and interleukin-6 (IL-6) by alveolar macrophages (AM) from allergic asthmatics developing a late asthmatic reaction after bronchial allergen challenge. In order to explain the modalities of this monokine synthesis, we tested in vitro the effect of an IgE-dependent stimulation on blood monocytes (BM) and AM from control and asthmatic subjects. TNF and IL-6 secretions were evaluated in 24-h supernatants by radioimmunoassay and by the 7TD1 cell proliferation test, respectively. AM from allergic asthmatics secreted spontaneously higher concentrations of TNF and IL-6 than did BM or AM from control subjects. BM from asthmatics also produced spontaneously increased levels of TNF, but at a lesser degree than did AM. The addition of anti-IgE induced a significant increase of TNF and IL-6 secretions by mononuclear phagocytes from control subjects only after previous sensitization with IgE-rich medium. In contrast, the direct stimulation by allergen or anti-IgE of AM and BM from asthmatics enhanced significantly the production of TNF and IL-6 when compared with cells cultured in medium alone. In these conditions, IgE-dependent activation of cells from allergic asthmatics compared with those from control subjects increased monokine production in a similar manner. Costimulation by recombinant human interferon gamma and IgE-dependent triggering had a synergistic effect on TNF production, but it had only an additive action on IL-6 synthesis (respective increase index: 9.8 compared with 2.9 and 9.8 compared with 2.1, respectively, for BM from control and asthmatic subjects).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1519862 TI - Pulmonary hemodynamics and lung function during chronic paraquat poisoning in sheep. Possible role of reactive oxygen species. AB - The purpose of this study was to establish a chronic model of paraquat-induced lung injury. To examine the role of reactive oxygen species in this form of lung injury, we measured malondialdehyde (MDA) and superoxide dismutase (SOD) activity in the lungs. Paraquat (5 mg/kg intramuscularly) caused a significant decrease in dynamic lung compliance from 128.5 +/- 9.2 to 63.3 +/- 11.8 ml/cm H2O (p less than 0.05), with a significant increase in AaPO2 3 wk after paraquat. Histologic findings in the lungs showed a gradual increase in the number of granulocytes and alveolar wall thickening with proliferation of reticular fibers and were coincident with the changes in physiology. A transient decrease in pressor responses to hypoxia was observed 1 wk after paraquat, although pulmonary hemodynamics did not change. The amount of lung MDA 3 wk after paraquat increased from the baseline value of 0.73 +/- 0.04 to 1.12 +/- 0.10 nmol/mg protein (p less than 0.05). SOD activity in the lung tissue significantly decreased from 6.47 +/- 0.20 to 4.82 +/- 0.25 U/mg protein (p less than 0.05) 1 wk after paraquat and remained at low levels for 3 wk. These findings suggest that a small dose of paraquat causes chronic lung injury characterized by granulocyte infiltration and lung fibrosis. Reactive oxygen species may play an important role in this chronic lung injury, and the inability to increase antioxidant defense may contribute to the reaction. PMID- 1519863 TI - Delta F508 mutation of cystic fibrosis gene is not found in chronic bronchitis with severe obstruction in Japan. AB - Diffuse panbronchiolitis (DPB) in Japan is a chronic bronchitis observed in nonsmoking adults, with severe obstruction and poor prognosis. DPB shares pathologic and clinical characteristics with mild adult cystic fibrosis (CF), except that CF is frequent in whites (Europeans and Americans of European descent) but not in Japanese. Recently, the cystic fibrosis transmembrane conductance regulator (CFTR) gene was identified, and a 3-base pair deletion (delta F508) was confirmed as a major mutation responsible for CF. We extracted genomic DNA from white blood cells of 17 DPB patients and from paraffin-embedded tissues of 4 DPB patients at autopsy. Two polymerase chain reaction (PCR) primers were made in exon 10 of the CFTR gene so that a three-base shorter segment of 78 base pairs was amplified from the CFTR gene with the delta F508 mutation; the DNA segment amplified from the normal gene contains an F508 area with 81 base pairs. Every DNA segment amplified from DPB patients showed a normal 81-base pair length, indicating no DNA sample contained the delta F508 mutation. These results based on delta F508 mutation analysis in the CF gene indicate that DPB may represent a disease different from CF. PMID- 1519864 TI - Effect of inspiratory flow rate on respiratory output in normal subjects. AB - We wished to determine the independent effect of inspiratory flow rate (VI) on respiratory output in the awake state. Seven normal subjects were connected to a volume-cycled ventilator in the assist/control mode. While the tidal volume setting remained constant, inspiratory flow rate was increased in steps (3 to 4 min each) from 30 to 90 L/min and then back to 30 L/min. Flow pattern was square, and all breaths were subject-triggered. Spontaneous respiratory rate (f) increased in all subjects as VI increased. Mean (+/- SD) f at 30 and 90 L/min were 8.8 (+/- 1.7) and 14.1 (+/- 4.4) min-1, respectively (p less than 0.01). VE increased (10.1 +/- 1.9 at 30 L/min to 16.3 +/- 5.6 at 90 L/min p less than 0.01) and the percentage of end-tidal CO2 decreased (4.7 (+/- 0.5) at 30 L/min to 3.3 (+/- 0.7) at 90 L/min (p less than 0.01)). The response was graded and reversible. The change in f was nearly complete within the first two breaths after transition, and there was no systematic tendency for f to change beyond this early response. The rate of change in airway pressure prior to triggering (dp/dt) increased as VI increased (5.3 +/- 2.0 cm H2O/s at 30 L/min to 10.8 +/- 2.6 cm H2O/s at 90 L/min; p less than 0.01). We conclude that inspiratory flow rate exerts an excitatory effect on respiratory frequency and on the rate of rise of inspiratory activity in conscious humans. This may be relevant to the mechanism of ventilatory response to various respiratory stimuli and to the management of patients receiving mechanical ventilation. PMID- 1519865 TI - Reference values of maximal respiratory mouth pressures: a population-based study. AB - The aim of our study was to measure values of maximal inspiratory (MIP) and expiratory (MEP) mouth pressures in 625 (266 male, 359 female) clinically and functionally normal subjects drawn out of a sample representative of the general population. MEP (near TLC and FRC) was found to be significantly higher when compared with MIP (near RV and FRC), and pressures in male subjects were significantly higher than those in female subjects. MEP values at TLC and FRC were found to be closely related, as were values of MIP near RV and near FRC. Among the tested body-size variables, body surface area (BSA) for all parameters had the highest degree of correlation. Stepwise linear regression analysis was performed to define the equation of normality for all four parameters, employing BSA, sex, age, and relative interaction terms. R2 values, although the variables employed for the equations were highly significant, were relatively low and didn't fully explain the source of variability. The influence of age was smaller than the influence of BSA, although age did reduce the unexplained variance in MEP and MIP. These results confirm that the most useful employment of MIP and MEP is to monitor their changes in each patient, but they point out, however, the usefulness of reliable reference equations. PMID- 1519866 TI - Pulmonary edema associated with salt water near-drowning: new insights. AB - In this case report we describe the clinical and laboratory findings of a man who nearly drowned after aspirating a large quantity of seawater. The aspiration of salt water, which is strongly hypertonic with respect to plasma, resulted in severe pulmonary edema, both from the quantity of aspirated seawater and the osmotically driven ultrafiltrate of plasma that accumulated in the air spaces. The initial concentration of protein in the edema fluid sample was very low, 0.7 g/dl, consistent with only a minimal increase in epithelial permeability. Approximately 4 h later, there was a marked increase in the concentration of protein in the residual alveolar fluid associated with improvement in several clinical indices, indicating that the excess alveolar fluid was reabsorbed very rapidly. In addition, the magnesium concentration was markedly elevated because of the aspiration of magnesium-containing seawater, which may have diagnostic importance for near-drowning in salt water. The data from this case provide evidence for well-preserved alveolar epithelial barrier function after aspiration of large quantities of hypertonic salt water. PMID- 1519867 TI - Improved diaphragmatic function after surgical plication for unilateral diaphragmatic paralysis. AB - We studied pulmonary function tests, maximal voluntary ventilation, arterial blood gases, and respiratory muscle strength and recruitment pattern in a 37-yr old symptomatic man before and after surgical plication for a left unilateral diaphragmatic paralysis. After plication, FVC, FEV1, TLC and FRC increased, whereas residual volume remained unchanged. Arterial PO2 improved from 70 to 87 mm Hg. Diaphragmatic strength, as expressed by the maximal transdiaphragmatic pressure increased from 30 to 75 cm H2O, and maximal voluntary ventilation increased from 74 to 123 L/min. Ventilatory muscle recruitment also changed: there was a shift from a positive to a negative delta Pg/delta Ppl slope during tidal breathing. This indicates more effective diaphragmatic recruitment after the procedure. We conclude that surgical plication may be of benefit to patients with symptomatic unilateral diaphragmatic paralysis. The improvement is due to improved respiratory muscle function. PMID- 1519868 TI - Corticosteroid-induced myopathy involving respiratory muscles in patients with chronic obstructive pulmonary disease or asthma. AB - We made observations on two patients with asthma and one with COPD who developed steroid-induced myopathy during prolonged treatment with high doses of corticosteroids. On admission, quadriceps force was on the average reduced to 31% of predicted (range 16 to 46% of predicted, nondominant leg), and urinary excretion of creatine in 24 h averaged 687 mg (range 275 to 1,045 mg/24 hr). Respiratory muscle involvement was evidenced by reductions in PImax and PEmax, being 38% (range 36 to 39) and 48% of predicted (range 36 to 68), respectively. Tapering of treatment with corticosteroids resulted in important recovery of quadriceps force and respiratory muscle force. In all three patients, a correlation between muscle forces and steroid dose was present during reduction of the dose. After 6 months quadriceps force averaged 62% of predicted (range 31 to 85), and PImax and PEmax reached 74% (range 52 to 92) and 92% of predicted (range 80 to 106), respectively, after 3 months. Consequently, respiratory muscle force appeared to recover faster than quadriceps force. The implications of these observations for patients treated with the usual doses of corticosteroids for shorter periods require further investigation. PMID- 1519869 TI - NHLBI workshop summary. Biology of lung preservation for transplantation. AB - The types of animal models that are used for assessing lung preservation, and the types of interventions that are likely to prove of value, must be carefully selected. For example, the events of warm ischemia are not necessarily the same as those that occur during cold preservation. Warm ischemia has often been used as a means of accelerating the degree of ischemic injury, but the events may not be qualitatively the same. Nonetheless, the use of different types of lung injury models contributes to our overall understanding of mechanisms of lung injury associated with transplantation. Pathologic studies of lung injury ischemia and reperfusion may not prove helpful, as they may be nonspecific and insensitive. To compare results of different preservation methods, a standardized animal model would be most helpful if a universally accepted one could be identified. This would include standard measurements of lung function, standard techniques of transplantation, and follow-up studies of several days' duration after transplantation. Such a model could serve as the ultimate test of preservation methods following its development in a variety of the animal models. It must be emphasized that whereas animal models generally begin with a normal lung that is preserved, the clinical situation differs because the donor lungs may be far from normal at the outset due to the effects of brain death, hemodynamic instability, infection, trauma, and a host of other factors. Thus, the limits of safe preservation in a clinical situation may well be significantly less than the safe preservation time demonstrated in the laboratory.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1519870 TI - Intersubject variability in particle deposition does not explain variability in responsiveness to methacholine. PMID- 1519871 TI - Assessment of the extent of implementation of the recommendations made in occupational hygiene survey reports. AB - The extent of implementation of recommendations contained in field reports from the Occupational Hygiene Unit of the Institute for Occupational Health at the Tel Aviv University, was investigated. The results show that 33% were not carried out at all and 16% were only partially carried out. A number of factors influenced the extent of implementation, in particular the degree of involvement of the management in worker health and welfare, an active safety system in operation, the professional skill and seniority of the person in charge of safety, awareness by the workers of health and safety matters, the existence of a specific budget for health and safety and a regulatory system concerning occupational exposure. PMID- 1519872 TI - Vibrations--discriminant models and possibilities for prognosticating specific and non-specific effects on the organism. AB - The present study involved 290 workers from branches of industry in which they were exposed to intense vibration and 102 patients suffering from disease due to vibration. Some specific (physiological) indices for exposure to vibration, such as the sensation of vibration, cold provocation test, Doppler-ultrasound, etc., and some non-specific (biochemical) indices, such as blood lipids, electrolytes and trace elements were studied. A discriminant analysis was made and 17 discriminant models (including different numbers of physiological and biochemical indices, age, and length of service) were elaborated. These models were used to predict the presence or absence of concomitant diseases, such as hypertension, coronary heart disease and arthritic lesions in persons exposed to vibrations; the stage of the vibration disease; the occurrence of exposure to vibration or of vibration disease. It was shown that physiological (specific) and biochemical (non-specific) indices affected by the exposure to vibration were interrelated, and that their estimation by means of the discriminant analysis revealed the distinction between the states mentioned above. PMID- 1519873 TI - Ferruginous body counts in sputum as an index of past exposure to mineral fibres. AB - Previous work by our group among vermiculite miners exposed to fibrous tremolite demonstrated that asbestos body counts in sputum closely reflected intensity and duration of past exposure. In the present project sputum samples from nearly 600 volunteers from 11 cohorts of workers exposed to asbestos and other mineral fibres were found to contain much lower numbers of asbestos bodies than had been observed in vermiculite workers and these counts did not reliably reflect past levels of exposure. No evidence was found that occupational exposure to man-made mineral fibres led to any ferruginous body formation. Asbestos body counts appeared to differentiate between mesothelioma cases and controls and between levels of radiological asbestosis, but in both comparisons, based on small numbers, the power of discrimination was low. Substantial variation was found both in asbestos body and in macrophage counts in daily sampling of vermiculite workers but it was not sufficient to invalidate comparison between groups for epidemiological study. In individual subjects, however, little reliance can be put on results from a single sputum sample, particularly if negative. PMID- 1519875 TI - Quantification of biological variability. AB - Pharmacokinetic models are usually developed to describe the kinetic behaviour of the chemical compounds in an average human body. There are however many situations were the effects of variations in a given pharmacokinetic parameter would be of interest. For example, in biological monitoring, the variability of biological data is a critical parameter when relating air and biological measures of an individual exposure. This paper reviews two possible approaches for the simulation of such variability in occupational pharmacokinetics. In the first, a simple one-compartment model is used together with statistical distributions for the intake and elimination of the compounds involved. Based on realistic distributions, this simple model is applied to the comparison of biological and air monitoring to estimate workers' exposure. The second involves a seven compartment physiologically based pharmacokinetic model, which includes provision of the means to input satistical distributions for some of the parameters: exposures, physical workload, body height, body weight, liver function and renal function. It makes it possible to predict the pharmacokinetic response of groups of workers, who differ in their exposures and in their physiological parameters. Realistic statistical distributions are then used to describe biological monitoring variability. The advantages and disadvantages of both the simple pharmacokinetic model and the physiological model are discussed in the context of predicting and understanding variability in occupational situations. Other potential developments are also considered. PMID- 1519874 TI - A survey of chronic bronchitis among brassware workers. AB - A stratified random sample of 580 workers aged between 18 and 50 years representing each sub-occupation in the brassware industry was studied for the prevalence of chronic bronchitis in relation to occupational and environmental factors. The findings were compared with those obtained in a reference group (N = 131) belonging to similar socio-economic status and unexposed to a dusty environment. Although the exposed group showed higher prevalence of chronic bronchitis in comparison to that observed in the controls (10.5 vs 5.3%), the difference was not significant at the 5% level. It was observed that the workers engaged in non-dusty occupations such as brass sheet cutting and engraving showed the lowest prevalence of the disease (5.0%) while those engaged in the dusty occupations viz., casting, soldering, electroplating and polishing showed the highest prevalence (12.0%). The smoking adjusted odds ratios calculated in various sub-occupations showed the highest risk of developing chronic bronchitis among the polishers (2.74). Though the risk in other occupational sub-groups was double, it did not attain a level of significance. The smoking adjusted odds ratios in relation to length of exposure showed that the risk was significantly higher among the workers exposed for over 10 years compared to those who worked for less than 10 years in the grinding, soldering and brass ingot making operations. The study thus showed a dose-response relationship between length of exposure and chronic bronchitis while effect of age on the disease was not discernible probably due to the small number of cases and the young age of the study group. The concentration of various metals in the air samples drawn from the work environment where main processes were in operation, was low compared to the prescribed level by ACGIH. PMID- 1519876 TI - Teamwork in surgery. PMID- 1519877 TI - Postgraduate surgical education in Singapore. PMID- 1519878 TI - The combined surgical meetings: the early days. PMID- 1519879 TI - Howard Eddey and his contribution to surgical education in Singapore. PMID- 1519880 TI - The extended lateral arm flap: a detailed anatomical study. AB - The lateral arm flap has long been the workhorse of microvascular surgeons in the cover of small and moderate-sized defects, especially in the head, neck, and the extremities. Its versatility, however, has always been restricted by its small skin paddle. The flap traditionally is harvested from the upper arm. This flap derives its blood supply from cutaneous perforators of the posterior radial collateral artery (PRCA) which forms an anastomotic plexus with the interosseous recurrent artery around the lateral aspect of the elbow. As a result of anatomical dissection and dye injection studies, we have re-defined the cutaneous blood supply of the PRCA which is found to continue for some distance into the forearm, and utilise this finding to design an "extended" lateral arm flap for use in microvascular reconstruction. PMID- 1519881 TI - The Oriental nose: an anatomical basis for surgery. AB - Fifteen Oriental noses were examined macrosurgically and microscopically. Five soft tissue layers overlying the osseocartilaginous framework are identified: the skin, the subcutaneous areolar plane, the vascular-fibromuscular layer, the deep areolar plane and perichondrium/periosteum. Two natural planes of dissection are represented by these areolar planes which separate the nose into an overlying skin envelope, a vascular-fibromuscular layer and an underlying osseocartilaginous framework. The cartilaginous framework provides projection, support and shape to the dorsum and tip of the nose but not to the alar lobule as this is devoid of cartilage. As there is no cartilage in the Alar lobule, the term 'Alar Cartilage' is misleading and the term 'Tip Cartilage' is introduced to replace it. The skin of the nose is specialised and has the ability to retain its shape even after dissection. This is due to an arrangement of elastin fibres in the upper dermis and the subcutaneous areolar plane which confers elasticity to the skin especially in the region of the Alar lobule which is a skin and fibromuscular sandwich. The vascular fibromuscular layer is like a sheet draping the osseocartilaginous framework. The main arteries of the nose lie on this layer. Injection studies of the blood supply reveal many arterial variations but always a distinct alar artery, columellar artery and alar plexus that have not been previously named. The alar groove is a junction between the alar lobule which is soft tissue alone and the tip which is soft tissue, supported by cartilage. The alar groove lies over the lateral edge of the tip cartilage and here there is muscular attachment to the fibromuscular layer. PMID- 1519882 TI - Cardiothoracic surgery. PMID- 1519883 TI - Hand surgery. AB - A historical outline of the development of Hand Surgery in Singapore is presented. It traces its growth from the Orthopaedic Surgery Unit at General Hospital Singapore in the early 1950's, to the present times. During this period, the Singapore Society of Hand Surgery was established in 1982, the Department of Hand Surgery at the Singapore General Hospital in 1985 and the Hand and Reconstructive Microsurgery Department was officially established at the National University Hospital in 1990. PMID- 1519885 TI - Ophthalmology. PMID- 1519884 TI - Neurosurgery. PMID- 1519886 TI - Orthopaedic surgery. PMID- 1519887 TI - Paediatric surgery. PMID- 1519888 TI - Urology. PMID- 1519889 TI - B-mode real-time ultrasound assessment of vocal cord function in recurrent laryngeal nerve palsy. AB - B-mode real-time ultrasound was used to assess vocal cord function in six patients with recurrent laryngeal nerve palsy. The thyroid cartilage acted as an acoustic window through which the true cords appear as hypoechoic structures. Vocal cord palsy detected on ultrasound was compared with fibreoptic direct laryngoscopy and indirect laryngoscopy mirror examination. Good correlation was seen in all the cases. PMID- 1519890 TI - The effect of chemotherapy on soft tissue and bone healing in the rabbit model. AB - The effect of chemotherapy on soft tissue and bone healing was studied in a rabbit femoral fracture model. Adriamycin was administered at various intervals preoperatively. Results were compared against a control group in which adriamycin was omitted. Post-chemotherapy blood count profiles were monitored. All animals were operated on with a standard skin incision, osteotomy of the femur and fixation with an intramedullary wire. Soft tissue was assessed with daily clinical scoring and tested for wound breaking strength at two weeks postoperatively. Bone healing was assessed at the time of sacrifice six weeks postoperatively by four-point bending to failure. Clinical scoring of wounds did not show significant differences between control and adriamycin-treated groups. Results of wound breaking strength and four-point bending to failure showed significant impairment for animals given adriamycin four and seven days preoperatively, and no significant impairment when given 14 days preoperatively. CLINICAL RELEVANCE: Contrary to previous studies, our results suggest that it is feasible to combine neoadjuvant chemotherapy and early surgery without compromise of soft tissue healing. Our results show that adriamycin impairs bone healing. We postulate that adriamycin has a temporary and reversible inhibitory effect on bone biology. The clinical implications of these findings are discussed. PMID- 1519891 TI - The dropped big toe. AB - Surgical procedures for exposure of the upper third of the fibula have been known to cause weakness of the long extensor of the big toe post-operatively. The authors present three representative cases of surgically induced dropped big toe. From cadaveric dissection, an anatomic basis was found for this phenomenon. The tibialis anterior and extensor digitorum longus muscles have their origin at the proximal end of the leg and receive their first motor innervation from a branch that arises from the common peroneal or deep peroneal nerve at about the level of the neck of the fibula. However, the extensor hallucis longus muscle originates in the middle one-third of the leg and the nerves innervating this muscle run a long course in close proximity to the fibula for up to ten centimeters from a level below the neck of the fibula before entering the muscle. Surgical intervention in the proximal one-third of the fibula just distal to the origin of the first motor branch to the tibialis anterior and extensor digitorum longus muscles carries a risk of injury to the nerves innervating the extensor hallucis longus. PMID- 1519893 TI - Surgery for cardiac arrhythmias. AB - From March 1989 to March 1991, 17 patients underwent curative surgical ablation of cardiac arrhythmias at the Singapore General Hospital. In the supraventricular tachycardia group, 13 patients with the Wolff-Parkinson White syndrome (WPW) underwent surgical ablation of the accessory conduction pathway by the classical endocardial approach. Two patients who had atrioventricular nodal tachycardia (AVNRT) underwent surgical dissection around the atrioventricular node to divide one of the dual conduction pathway responsible for the tachycardia. In the ventricular tachycardia group, two patients underwent surgical ablation of the arrhythmic focus. There was no operative mortality in the supraventricular tachycardia group and there were no late deaths to date. All these patients underwent electrophysiological study just before discharge and most of them had a repeat test six months later. In the Wolff-Parkinson White group, surgical ablation was completely successful in 12 patients (92%), preexcitation recurred in one patient (8%) but non had recurrence of supraventricular tachycardia. The two patients who had atrioventricular nodal tachycardia were completely cured of recurrent supraventricular tachycardia and had normal atrioventricular conduction. In the ventricular tachycardia group, one was cured with no recurrence of tachycardia, is not on medication and is in New York Heart Association Class I status. The other died postoperatively of recurrent ventricular tachycardia and low cardiac output syndrome. PMID- 1519892 TI - Anti-toxoplasma serotitres in uveitis and ocular toxoplasmosis. AB - This study was based on anti-toxoplasma serotitres obtained from 80 normal healthy adults and 103 consecutive patients with anterior, posterior and panuveitis over a 42 month period. Twelve out of 80 (15%) normal healthy sera were found to have low titres (1:64 to 1:256), while 3 (3.8%) had high titres (1:1024 or higher). The distribution of serotitres in patients with clinical toxoplasmosis was significantly different from the population sample (p less than 0.001, chi-squared test). Similarly, the distribution of serotitres in patients with posterior uveitis (of which 28 out of 54 were clinically ocular toxoplasmosis) having serotitres of 1:1024 or greater, was found to be significantly different from the normal population (p less than 0.001, Chi squared test), but not statistically different from those with clinical ocular toxoplasmosis. Hence, anti-toxoplasma serotitre is useful as a diagnostic screening tool only in patients with posterior uveitis. It is also useful in confirming cases of suspected clinically positive ocular toxoplasmosis in our local population. PMID- 1519894 TI - Surgical management of intrathoracic aortic aneurysm. AB - The pathology, clinical features, indications for surgery and the results of intrathoracic aneurysm are analysed in thirty-nine consecutive patients who underwent surgery at Singapore General Hospital from January 1986 through December 1990. There were twenty cases of non-dissecting aneurysm and nineteen cases of dissecting aneurysm or aortic dissection. The 30 day survival for the twenty patients with non-dissecting aneurysm was sixteen patients (80%). The best results were obtained in patients with aortic root aneurysms. The overall 30-day survival for the nineteen patients with aortic dissection was twelve patients (64%). The mortality was especially high in patients with acute aortic dissection (46%). Recent advances in the management of these aneurysms make early recognition and diagnosis mandatory to achieve the best results. PMID- 1519895 TI - The pre-operative treatment of oesophageal carcinoma with synchronously administered chemotherapy and radiotherapy. AB - Forty-six patients with either squamous cell cancer of the oesophagus or adenocarcinoma involving the lower oesophagus have been treated with synchronously administered radiotherapy and chemotherapy (5FU & Cisplatin) prior to resection of the oesophagus. Endoscopically, complete regression of tumour occurred in 21 patients (46%) and when the oesophagus was resected in these patients, it was found that 11 of the resected specimens contained residual tumour deep to the mucosa. Thus, the actual complete regression rate in the 46 patients was 22%. The postoperative mortality rate was 13% (22% in the first half of the series and 4% in the second half). The median survival rate was 36 months in the 24 patients operated on for squamous cancer of the oesophagus, and 14.5 months in 18 patients operated on for adenocarcinoma of the cardia. Eight patients are alive and disease free at more than three years from surgery, and all of these patients had a squamous cell carcinoma, and all had a complete histological response from their preoperative radiotherapy and chemotherapy. PMID- 1519896 TI - Erectile dysfunction in Singapore men: presentation, diagnosis, treatment and results. AB - Three hundred and thirteen new cases were seen in more than two years at the Sexual Dysfunction Clinic at the Division of Urology, Toa Payoh Hospital (TPH). Patients were assessed by history, clinical examination, psychological evaluation, hormonal and biochemical tests; special investigations such as monitoring of nocturnal penile tumescence, cavernosography, selective pudendal arteriography and tests of neurological function were performed where indicated. Two hundred and twenty-seven patients (72.5%) had impotence due to organic causes while 86 patients (27.5%) were found to have psychogenic impotence. Diabetes mellitus and vascular disease account for the large proportion of organic impotence (81%). Patients with psychogenic impotence responded fairly well to psychosexual therapy and drug treatment in certain cases. Forty-four patients underwent medical therapy which consisted mainly of pharmacologically induced penile erections by the use of papaverine, phentolamine or prostaglandin E-1; 21 patients (48%) who were on self-injection therapy became non-compliant subsequently. One hundred and fourteen andropausal patients with low testosterone levels received hormonal replacement. Thirty-one patients underwent surgery- stripping and ligation of the deep dorsal vein of the penis (13 patients), microsurgical arterial revascularisation (two patients) and penile prosthetic implantation (16 patients). Our success rates for the operations were 54%, 100% and 88% respectively. PMID- 1519897 TI - Preliminary experience in ileal neobladder reconstruction. AB - In the treatment of transitional cell carcinoma of the bladder, the recent trend is towards radiation or chemotherapy which can be either regional or systemic. There have also been good results with giving Mitomycin or Bacillus Calmette Guerin instillation into the bladder for superficial tumours. There are occasions where patients present with large bulky tumours which cannot be controlled by endoscopic measures, invasion involving multiple sites and carcinoma in-situ which progresses to invasion. In these occasions, we have to resort to surgical clearance of the tumour. If it is possible, all patients would not like to wear a urinary bag for the rest of their lives. A bladder replacement if ever possible is always welcomed because the patient can pass urine from the natural passage. Due to the magnitude of a radical cystectomy and status of the urethra, it is not always technically possible to reconstruct the bladder. With improvement of operative techniques and suture materials, there has been a recent development of a method of bladder reconstruction that uses an ileal pouch. We report our early experience with this operation. PMID- 1519898 TI - Urological trauma. AB - Major urological trauma is life threatening and frequently associated with trauma to other organs. A conservative approach to lesser degrees of damage to the kidney is fully justified whilst a shattered kidney or a pedicle injury calls for surgical exploration. Renal injuries between these two extremes require careful assessment and clinical judgement to decide the best management. An intravenous urogram remains the mainstay of investigation but computed tomography, ultrasound and arteriography can be useful in some circumstances. The management of urethral trauma remains controversial and depends largely on the assessment of whether the posterior urethra is partially or completely ruptured. There remain two schools of thought concerning early or late intervention but all are agreed that suprapubic diversion is essential and that a urethral catheter should not be passed blindly in the initial stages. A ruptured bladder should always be repaired and early intervention is recommended for ureteric injuries. Severe trauma to the testis is best managed operatively to reduce the morbidity. PMID- 1519899 TI - Computerised 3-dimensional vector volume analysis--the role of a new method for assessing anal sphincter competence. AB - The results of manometric assessment (using conventional parameters) in idiopathic faecal incontinence overlap with normals, especially if the impairment is not severe. Computerised three-dimensional vector volume analysis is a recently introduced method of integrating the pressure profile along the anal canal in multiple radial directions, which may detect minor sphincter weaknesses more accurately. We compared the two methods in 47 subjects (normals = 25, patients with idiopathic faecal incontinence = 22), to analyse the same data derived from a station pull-through manometric technique. The conventional parameters of mean resting and maximum voluntary contraction pressures did not differ significantly between normal and incontinent subjects. The anal canal length in incontinent patients was significantly shorter (mean 2.9 SEM 0.2 cm in normals and 2.0 SEM 0.3 cm in incontinent; p less than 0.5). The computer calculated vector volumes and pressure symmetries (both at rest and during contraction) were not significantly different between the two groups. Although local areas of weaknesses may be identified on computerised vector diagrams, the vector volume calculations gave little additional objective information to the conventional indices to discriminate milder degrees of idiopathic faecal incontinence. PMID- 1519900 TI - Microsurgery and its clinical impact. AB - Microsurgery is a technique of magnifying the visual horizon of the surgeon to enable him to see better, dissect better and perform micro-manipulation. This is to help the surgeon to perform very precise surgery that was not possible in the past. The greatest impact has been in our ability to suture small vessels and to allow us to shift tissues readily from one part of the body to another. It can be considered as a form of "spare part surgery" by using biological tissue consisting of toe, digits, bone, cartilage, skin muscle, intestine and other organs for reconstruction. The techniques are now widely accepted as important techniques in reconstructive surgery. The increasing application of these techniques are now being seen more and more in limb preservation surgery for trauma, tumour resection, congenital abnormality and organ transplant. The potential wide application of the technique in hetero transplant, especially in foetal surgery and foetal tissue transplant is now limited only by immunological rejection. PMID- 1519901 TI - Current concepts in the treatment of soft tissue sarcomas. AB - Soft tissue sarcomas encompass a wide variety of lesions and continue to pose a different treatment problem. However the outlook is improving. Recent advances in pre-treatment assessment and pathological assessment of soft tissue sarcomas have resulted in more accurate clinical staging. In addition, recent advances in surgical adjuvant treatment programmes hold promise for better results. PMID- 1519902 TI - Metastatic bone disease: current concepts of clinicopathophysiology and modern surgical treatment. AB - Metastases to bone are a common problem confronting both the orthopaedic oncologist and cancer specialists. Early diagnosis requires a knowledge of the pathogenesis of bone metastases. A primary route of metastatic cells is via Batson's vertebral vein plexus. An understanding of the pathophysiology enables the surgeon to plan effective treatment. As many patients continue to survive for prolonged periods following the detection of bone metastases, it is important to plan treatment that is durable and functional. Non-operative treatment is utilised for small lesions (less than 25 percent of the cortical diameter). Radiotherapy (generally 3000 cGy in ten fractions), patient education (to avoid excessive torsional loads), and systemic chemotherapy or hormonal therapy are the mainstays of non-operative treatment. The indications for surgical treatment include: (1) lesions greater than 50 percent the diameter of the cortex, (2) permeative lesions in high stress areas (subtrochanteric region of the hip, mid femoral diaphysis, mid humeral metaphysis), and (3) lesions in which pain persists following external beam irradiation. Early and effective treatment improves the remaining quality of life in patients with metastatic bone disease. A knowledge of the pathogenesis and pathophysiology aids the clinician in making an early diagnosis. PMID- 1519904 TI - Challenges in surgery. PMID- 1519903 TI - Surgical management of anal incontinence. AB - The complex nature of the continence mechanism is reflected in the difficulties experienced in the surgical management of patients with faecal incontinence. Apparent anatomical abnormalities may be identified but the functional outcome following surgery may be unsatisfactory. It is therefore important to improve both the selection of patients as well as the surgical procedures themselves. Selection of patients for appropriate treatment should be based on clinical findings as well as anorectal physiology tests. Most patients referred for assessment fall into one of six categories: incontinence with a normal sphincter; minor incontinence due to local anal conditions; direct sphincter injury; neurogenic ("idiopathic") incontinence; rectal prolapse; generalised neurological condition. Minor anal conditions causing incontinence must be carefully identified for appropriate treatment. A large amount of work has been done over the past ten years on the pathophysiology of major incontinence and new surgical procedures have been developed. A common difficulty is deciding whether anterior sphincter attenuation or neurogenic weakness is the dominant lesion causing incontinence; overlapping sphincter repair is indicated for the former and postanal repair for the latter. Anorectal physiology studies can be helpful in differentiating these conditions and are now used routinely in the assessment of patients. PMID- 1519905 TI - Vascular trauma. AB - An arterial injury causes either major haemorrhage with hypovolaemia and shock or ischaemia in the distribution of the damaged vessel. Initial management consists of establishment of an airway and haemodynamic stabilisation. If there is persisting hypotension because of continuing bleeding, further resuscitation is carried out in the operating room. A rapid systematic examination is performed with a thorough evaluation of motor and sensory function, as vascular injuries are often accompanied by nerve injuries, which should be well defined prior to any attempts at vascular repair. Arteriography, if available promptly, is useful in stable patients. It allows assessment of the extent of injury and of distal vessels and may prevent unnecessary exploration of neck and extremity injuries. However, it should not delay the vascular repair beyond six hours from the time of injury. It is useful if the site of injury is unclear, the trajectory of a missile is unknown or there are multiple pellet injuries but it is unnecessary if there is an obvious vascular injury. It is helpful to have facilities available for intra-operative arteriography. Repair of arterial injury is performed whenever possible. Prolonged ischaemia, beyond six to eight hours, causes irreversible nerve damage and will lead to an unsatisfactory result, even if re vascularisation is successful. The principle of proximal and distal control and adequate debridement of damaged artery and surrounding tissue must be adhered to. The type of repair depends on the nature and extent of the arterial injury and includes lateral repair, end-to-end anastomosis and vein graft interposition.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1519906 TI - Holistic comfort: operationalizing the construct as a nurse-sensitive outcome. AB - The structural and semantic complexities of the construct of comfort are explicated and a rationale is presented for operationalizing the construct for holistic nursing practice and research. A review of the literature about comfort provides theoretical support for the concept's taxonomic structure, which was presented in an earlier publication and is modified in the present article. In addition to being useful for generating assessment tools for practice, the taxonomic structure of comfort can be utilized to develop instruments for outcome research. PMID- 1519907 TI - The influence of sociopolitical, scientific, and technologic forces on the study and treatment of neonatal pain. AB - This article describes how sociopolitical, scientific, and technologic forces have influenced neonatal pain research and clinical practice. Changing beliefs about pain from the perspective of patients, physicians, nurses, and scientists investigating the neurobiology of pain are discussed. The impact of the development of the specialty of neonatology and its associated technologic advances on neonatal pain is explored. In addition, the influence of increased scientific knowledge about the neurodevelopment of the neonate and neurobiology of the sensory system on neonatal pain is presented. Finally, changes in society's views of children and the role of parents are addressed. The article concludes with a discussion of the relative importance of each of the factors in stimulating recent interest in neonatal pain. The opportunities for nurses to contribute to scientific research to improve the care of neonates in pain are highlighted. PMID- 1519908 TI - Culture and pain: a Mesoamerican perspective. AB - Culture has been identified as a factor that influences a person's reaction to and expression of pain. Research in the area of pain and culture has not established a clear link between cultural meanings and attitudes associated with pain and pain behaviors. The purpose of this ethnohistoric study was to explore the beliefs related to the experience of pain within ancient Mesoamerica. The six themes that emerged from this study represent efforts related to the discovery of the epistemics of cultural meanings of pain in contemporary Mesoamerican cultures, specifically Mexican-Americans. These findings serve as a benchmark from which to understand Mexican-American meanings, expressions, and care associated with pain. PMID- 1519909 TI - Relieving pain through ordinariness in nursing: a phenomenologic account of a comforting nurse--patient encounter. AB - This article describes a nursing encounter between Sue, a nurse, and Becky, a patient. Sue and Becky related to one another through a sense of shared humanity that not only relieved some of Becky's pain, but also created some possibilities for changing patterns in her life that had been built up over a long period. The article suggests that nurses and patients relate to one another through their affinity as humans. Within the context of caring, nurses such as Sue are ordinary people perceived as being extraordinarily effective by the very ways in which their humanness shines through their knowledge and skills to make their whole being with patients something more than just professional helping. An implication for nursing knowledge arising from Sue's and Becky's interaction, and from the study generally, is the need to reconceptualize the nurse as person, so that nurses are described not only in terms of their professional roles and functions but also as people who share the everyday human qualities of their patients. PMID- 1519910 TI - Undermedication for pain: an ethical model. AB - Ethical decision making for, and with, clients experiencing pain and needing narcotic analgesia is especially problematic as evidenced by research findings. This article demonstrates the application of Greipp's model to ethical decision making for clients experiencing pain. Particular attention within this model is given to learned potential inhibitors of the nurse as they influence the outcome (decision). The application of this model to decision making and pain management will generate further scientific inquiry by identifying the areas of breakdown in ethical decision making for and by clients experiencing pain so that remediation strategies may be planned. PMID- 1519911 TI - A descriptive study of nursing judgment in the assessment and management of cardiac pain. AB - Unrelieved cardiac pain in patients admitted to a coronary care unit (CCU) with a diagnosis of coronary artery disease was examined from the perspective of nursing judgment. The purpose of this study was to reveal expert clinical knowledge and judgment in this specific area of critical care practice. Using a naturalistic approach, nurses were observed and interviewed as they made judgments about cardiac pain. Qualitative data analysis identified patterns of nursing actions and thought processes. Findings indicated that clinical knowledge of the titration of drugs was used in the treatment of cardiac pain, and qualitative distinctions and sense of saliency were also important in pain assessment. Intuitive thought processes were identified in the clinical judgment of expert nurses. PMID- 1519912 TI - The dyspnea experience: nociceptive properties and a model for research and practice. AB - Dyspnea has been defined as the unpleasant sensation of difficult breathing and the reaction to that sensation. Dyspnea research, however, has largely used a unidimensional, sensory model of dyspnea devoid of the affective and motivational dimensions that uniquely characterize this sensation in clinical populations. Dyspnea might be more comprehensively viewed as a nociceptive phenomenon which, like pain, has affective dimensions expressed as distress in response to aversiveness. A multidimensional, ecologic model of the dyspnea experience is presented that incorporates nociceptive sensation properties and is suggestive of new directions for dyspnea research uniquely relevant to nursing science. PMID- 1519913 TI - The meaning of pain management: a concept analysis. AB - As it relates to the person experiencing chronic nonmalignant pain, the conceptual meaning of pain management has not been clarified previously. This article describes a concept analysis of pain management that resulted in a definition of the term and three defining attributes: pain relief, pain modulation, and self-efficacy. A model case is provided with examples of borderline and related cases. The findings of this analysis will contribute to instrument development, theory testing, and an understanding that should positively impact the self-management of persons experiencing chronic nonmalignant pain. PMID- 1519914 TI - Effect of fermented oatmeal soup on the cholesterol level and the Lactobacillus colonization of rat intestinal mucosa. AB - Rats were fed with freeze-dried oatmeal soup fermented by six different Lactobacillus strains from rat and man; the formula is intended for enteral feeding. The serum cholesterol levels after 10 d were lower for rats eating oatmeal as compared to a commercial product, Biosorb Sond. Colonizing ability of the administered strains were evaluated in vivo. Only Lactobacillus reuteri R21c were able to, effectively, colonizing the mucosa; it represented about 30% of the Lactobacillus population 24 d after termination of the administration. L. reuteri R21c was easily recognized by the ability to produce a yellow pigment on agar plates. The identity was confirmed by carbohydrate fermentations (API 50CH), plasmid pattern and endonuclease restriction analysis of the chromosomal DNA. PMID- 1519915 TI - Genetic analysis of methylotrophic yeast Candida boidinii PLD1. AB - This paper reports the initial experiments for genetic analysis of the haploid methylotrophic yeast Candida boidinii PLD1. The collection of multiply marked auxotrophic mutants was obtained after treatment with UV-light or X-rays. Protoplasts from several mutants were fused by the PEG-CA2+ technique and five prototrophic hybrids were isolated. The genetic structure of the hybrids was studied by means of spontaneous and induced mitotic segregation. Our data suggest that hybrids are diploids, heterozygous by parental auxotrophic markers. We obtained genetic linkage between mutations lys2-8-met-3 from one hand and ade-17 arg-24 from the other. The genetic maps constructed showed similar characteristics concerning both the order of the markers and their map distances. PMID- 1519916 TI - Physical and genetic characterization of linear DNA plasmids from the heterothallic yeast Saccharomycopsis crataegensis. AB - Five strains of the heterothallic yeast Saccharomycopsis crataegensis have been previously shown to contain DNA and/or RNA plasmidlike molecules (Shepherd et al. 1987). Three DNA plasmids, designated pScrl-1, -2 and -3, were found in strain NRRL Y-5902, while two were identified in each of NRRL strains Y-5903 and Y-5904. DNA plasmids were not identified in S. crataegensis strains Y-5910 or YB-192. Four S. crataegensis strains (Y-5903, Y-5904, Y-5910 and YB-192) were also shown to possess double-stranded RNA (dsRNA) molecules not found in strain Y-5902 (Shepherd et al. 1987). Hybridization studies now demonstrate the DNA plasmids in Y-5903 and Y-5904 to be highly homologous to their respective size counterparts (pScrl-1 and pScrl-2) in Y-5902 and to show some homology to pScrl-3. Restriction endonuclease mapping studies confirm the linear nature of each plasmid and establish identical restriction maps for a 1.4 kilobase (kb) region in pScrl-2 and -3. This 1.4 kb region accounts for the hybridization homology of pScrl-2 and pScrl-3 noted by Shepherd et al. (1987) and for homology of the plasmids of Y 5903 and Y-5904 to pScrl-3 of Y-5902. The pScrl plasmids show no homology to the dsRNA molecules of S. crataegensis, the 2 microM circular DNA of Staccharomyces cerevisiae, the 'killer' plasmids of Kluyveromyces lactis, or the linear DNA plasmids of Pichia inositovora. In crosses between linear DNA plasmid-containing and dsRNA-containing strains, only progeny containing the pScrl plasmids were recovered. Poor spore viability and a lack of complete tetrad recovery limited the extent of the analysis, but the findings suggest a cytoplasmic mode of inheritance for these linear DNAs. PMID- 1519917 TI - Adhesive knob formation by conidia of the nematophagous fungus Drechmeria coniospora. AB - We studied conidiogenesis and adhesive knob formation (maturation) by newly developed conidia of the nematophagous fungus Drechmeria coniospora. Upon conidiogenesis on infected nematodes or during saprophytic growth of the fungus in axenic cultures compact clusters of conidia developed. Less than 10% of such clustered conidia matured; mature conidia were invariably located on the periphery of the clusters. The kinetics and rate of maturation of conidia were studied in in vitro systems and in soil. In both cases adhesive knobs were formed; the rate at which knobs were formed appeared to be determined by the age of the conidia, the temperature and the soil moisture. In addition, knob formation was suppressed at increasing conidial densities. Under favorable conditions, however, over 90% of the conidia matured within a period of 3 days. The rate of knob formation was neither influenced by the presence of nematodes nor by that of exogenous nutrients, which suggests that maturation is an autonomous process. Electron-microscopical analysis indicated that budding of the conidia at the initial stage of maturation occurred simultaneously with the deposition of the sticky, adhesive layer around the wall of the developing knob. The ecological significance of the time- and spatially separated maturation of conidia after conidiogenesis is discussed with respect to survival of the conidia. PMID- 1519918 TI - Isoprenoid quinones and fatty acids of Zoogloea. AB - Nine Zoogloea strains including the type strain of Z. ramigera (IAM 12136 = ATCC 19544 = N.C. Dondero 106) and newly isolated strains were investigated for isoprenoid quinone composition and whole-cell fatty acid profiles. Seven of the tested strains, having phenotypic properties typical of Zoogloea, were characterized by their production of both ubiquinone-8 and rhodoquinone-8 as major quinones, whereas the remaining two strains, Z. ramigera IAM 12669 (= K. Crabtree I-16-M) and IAM 12670 (= P.R. Dugan 115), formed ubiquinone-10 and ubiquinone-8, respectively, as the sole quinone. All rhodoquinone-producing strains contained palmitoleic acid and 3-hydroxy-decanoic acid as the major components of nonpolar and hydroxylated fatty acids, respectively. Marked differences were noted in the fatty acid composition between the strains with and without rhodoquinones. The chemotaxonomic data suggested that the rhodoquinone lacking strains should be excluded from the genus Zoogloea. Since there have been no reliable taxonomic tools for Zoogloea, rhodoquinone analysis may provide a new criterion of great promise for identifying Zoogloea strains. PMID- 1519919 TI - Genetic identification of natural Saccharomyces sensu stricto yeasts from Finland, Holland and Slovakia. AB - Genetic and karyotypic studies of natural Saccharomyces sensu stricto yeasts from Finland, Holland and Slovakia revealed three wild sibling-species: Saccharomyces cerevisiae, Saccharomyces bayanus and Saccharomyces paradoxus. PMID- 1519920 TI - Sporobolomyces lactosus, a new species of ballistosporous yeast equipped with ubiquinone-10. AB - A new species of ballistospore-forming yeasts was recovered and its description given. Sporobolomyces lactosus, isolated from activated sludge treating petrochemical wastes, produces pinkish-coral to pink colored colonies, assimilates lactose and has Q-10 as the major ubiquinone. PMID- 1519921 TI - [Surgical treatment of gastric cancer in the aged]. AB - The present status of surgical treatment for gastric cancer in the aged was reviewed. The incidence among the aged in the overall operated patients with gastric cancer has increased yearly and recently has reached approximately 35%. The incidence of early gastric cancer in the aged has increased 40% in recent times. Pulmonary failure and anastomotic leak of the alimentary tract are the most common post-operative complications in the aged; these easily lead to the development of multiple organ failure with high mortality. Precise pre-operative evaluation of functional disorder in each organ and pre-, post-operative nutritional and transfusional support is indispensable to overcome these complications. Surgeons are required to perform appropriate surgical maneuvers with minimum operation time and minimum blood loss with full consideration for the adequate surgical indication in accordance with both the spread of the cancer and the general condition of the aged patient. Mental care to avoid post operative mental disorders is also crucial. PMID- 1519922 TI - [Indication and problems of radiation therapy of elderly patients with cancer]. AB - The incidence of cancer and the patients treated with radiation therapy increased with age. Of 5778 patients treated with radiation therapy at the Center for Adult Diseases, Osaka, 37.5% are over 65, and 10.8% are over 75 years old. Older patients with cancer have a lower survival rate. Patients over the age of 75 with carcinoma of the pharynx, esophagus, lung, and uterine cervix have decreased survival compared with younger patients. However, for the patients with carcinoma of the larynx, age is not a determinant of prognosis. With respect to radiation therapy, it is not clear whether elderly patients differ from younger ones in responsiveness. However, a decreased tolerance for radiation therapy might be expected and under-dosing with radiation therapy may be more prevalent. More study of the optimal management of elderly patients with cancer is needed. PMID- 1519923 TI - [Chemotherapy in the elderly]. AB - Because of the increase in the incidence of malignancies with advancing age, we have need to make decision on the chemotherapy of elderly patients with cancer. However, until recently, studies about response to treatment and toxicities in the elderly patients have been quite limited. Many of clinical trials have excluded elderly patients with advanced cancer. In leukemia and Hodgkin's lymphoma, definite trends of decreased levels of response and survival in relationship to increased age have been reported. This reduced rates of response in elderly leukemia patients do not appear to be due to chemotherapy resistance but rather to high rates of death among elderly patients during remission induction therapy or to inadequate salvage therapy. On the other hand, older patients with solid cancers can be treated with chemotherapy as successfully as younger patients. General expectations of response, remission, and survival are similar for the older and younger patients. With the exception of small increase in the incidence of hematologic toxicity in the older group, both younger and older patients experience the same frequency of toxic reactions. Aging is a highly individualized process that cannot be defined by chronological landmarks. Therefore, it can be said that there is no reason to exclude from adequate chemotherapy, simply on the basis of age alone. But, observations on the proper role of chemotherapy in older patients are very limited, and further studies are needed in this area. PMID- 1519924 TI - [Electron microscopic study on the method of evaluation of SRC assay]. AB - The subrenal capsule assay (SRC) is a rapid and precise method for evaluation of chemotherapeutic agents. However, it seems to present some difficulties with regard to sensitivity, since evaluation is done by measurement of graft size. In this study, SRC was performed on six clinical cases of colorectal cancer using nude mice, which were given UFT 15 or 20 mg/kg orally or 2.5 mg/kg CDDP subcutaneously for 2-6 days. Histological changes in the grafted tumors were then observed by electron microscopy. Mucous granules and other features were assessed for evaluation of assay sensitivity. The number of mucous granules seemed to be the most reliable parameter that paralleled the sensitivity evaluated by tumor diameter. Other features such as nuclear mitosis, lysosomal increment and abnormal accumulation of ribosomes, had little correlation with sensitivity. However, further exploration is warranted with regard to local defects of the cytoplasm. This ultrastructural examination suggested that grafted tumor cells were damaged slightly by implantation under the renal capsule, and that the SRC using tumor size as a parameter is clinically useful under conditions where the tumor xenografts show good viability and proliferation in the control group. PMID- 1519925 TI - [Serum concentration of HCFU and 5-FU after oral administration of HCFU in postoperative digestive cancer patients]. AB - In an attempt to establish the optimum dose of HCFU, the effect of the presence of stomach on the absorption of HCFU and both the rise and maintenance of blood HCFU levels was evaluated in patients with gastric cancer (total gastrectomy group) and with colorectal cancer (non-gastrectomy group). The blood concentrations of HCFU fractions and 5-FU were determined in terms of pharmacokinetic parameters in these groups. The Tmax was significantly different between the two groups, with HCFU fraction and 5-FU levels that were significantly higher in the total gastrectomy group 30 minutes after administration. No differences were found in Cmax or AUC. There were no significant differences in Cmax or AUC among the various subgroups given different doses of HCFU (100, 150 and 200 mg) in either group, although dose dependency was observed. Similar results were obtained in crossover tests. The 5 FU remained at an effective concentration of 0.05 microgram/ml, 4 hours after a single dose of 100 mg HCFU. PMID- 1519926 TI - [Neo-adjuvant chemotherapy with tegafur suppository for rectal cancer--evaluation of the antitumor effects, tissue levels of 5-FU and inhibition of thymidylate synthase. Tochigi Colorectal Cancer Study Group]. AB - We evaluated antitumor effect histologically and assayed the tissue levels of 5 fluorouracil (5-FU) and thymidylate synthase (TS) activity using surgical specimens obtained from the patients with rectal cancer, who were given tegafur suppositories prior to surgery. The antitumor effect was evaluated histologically according to classification of the general rules for the gastric cancer study (Japanese Research Society for Gastric Cancer). In 39 patients, 16 tumor specimens revealed no effect (grade-0), 22 tumors grade-1 effect, and one was not evaluable because of the severe inflammatory changes. In 23 of these patients, resected specimens were available for the assay. 5-FU levels in cancer tissues were significantly higher than those in normal tissues, and TS inhibition rates (TSIR) were almost identical, averaging around 20%, in both cancer and normal tissues. Comparing the 5-FU levels and TS activity according to the histological effects (i.e.: 'grade-0' vs 'grade-1'), the 5-FU levels in the tumors achieved grade-1 were significantly higher than in the tumors showed 'grade 0' (p less than 0.01), and TSIR in the former were relatively greater than in the latter (p = 0.053). It is suggested that both tissue levels of 5-FU and TSIR may be useful parameters to predict the anti-tumor effect against rectal cancer after administration of 5-FU and its derivatives. PMID- 1519927 TI - [Pharmacokinetics and toxicological study on the intraperitoneal administration of cisplatin and etoposide in gynecological malignancies]. AB - We administered cisplatin and etoposide into the peritoneal cavity of 13 postoperative patients with gynecological malignancies, and studied the pharmacokinetics and toxicity in the combination of both drugs. Cisplatin 100 mg/body and etoposide 200 mg-400 mg/body were mixed together in 500 ml or 1,500 ml of normal saline and administered intraperitoneally on the day of operation and two or three weeks later. The peritoneal peak level of free cisplatin, diluted with 500 ml, was about two times higher than that, diluted with 1,500 ml. However, there was no difference in the peritoneal and plasma AUC. The peritoneal level and AUC of etoposide, diluted with 500 ml, was about two times higher than that, diluted with 1,500 ml. Among the groups of 1,500 ml, peritoneal and plasma levels and AUC were almost proportional to the doses. Nausea and vomiting were experienced in all patients. With the increase of etoposide, more marrow suppression was observed. However, we encountered no other significant side effects. In conclusion, intraperitoneal administration of cisplatin and etoposide in this setting can be used safely with minimum side effects, and the dilution of 1,500 ml seems to be better. PMID- 1519928 TI - [Transient subacute encephalopathy induced by high-dose methotrexate treatment in children with acute lymphoblastic leukemia and malignant lymphoma]. AB - Transient subacute encephalopathy was detected in 4 of 83 patients undergoing treatment with high-dose methotrexate (HD-MTX) and citrovorum factor rescue for childhood acute lymphoblastic leukemia and malignant lymphoma from 1984 to 1991. Subacute encephalopathy occurred in relatively older patients and early in the course of treatment with HD-MTX. The average interval between the HD-MTX course and the onset of the neurologic disturbance was 6.5 days. All 4 patients treated had no neurological sequelae. Laboratory evaluations disclosed nontoxic plasma MTX levels at onset of symptom and not detected in liquor. CT in 4 patients disclosed no abnormality, but MR images revealed abnormal signal intensity patterns of cerebral white matter in 2 cases. In one case the abnormal MR finding resolved after 3 months. The pathogenesis of this neurologic symptom remains unknown, but further HD-MTX treatment may be acceptable in follow-up of MR image, because the prognosis of subacute encephalopathy seems favorable. PMID- 1519929 TI - [Short-duration bladder instillation therapy with pirarubicin for superficial bladder tumor based on pharmacodynamic study]. AB - From our experimental study, an instillation of THP for 5 minutes was attempted in 23 patients with superficial bladder tumors. THP (30 mg dissolved in 50 ml of distilled water) was instilled into the bladder 6 times every 48 hours. Of 23 patients, 9 (39%) showed complete disappearance of the bladder tumors, while partial disappearance (more than 50% tumor reduction) was observed in 3 cases (13%). Therefore the overall response rate was 52%. Neither urinary frequency nor hematuria was observed in all the cases, while painful urination was observed in 3 cases (13%). This newly designed bladder instillation therapy was effective against superficial bladder tumors with low incidence of local side effects. PMID- 1519930 TI - [Chemotherapy-associated hemolytic uremic syndrome--a case report]. AB - A 63-year-old male had undergone combination chemotherapy including adriamycin, cisplatin, mitomycin C, 5-fluorouracil and vindesine for six months for double cancer of esophagus and stomach. He complained of lassitude during therapy, and laboratory examinations revealed microangiopathic hemolytic anemia, thrombocytopenia and hyperbilirubinemia. Despite administration of prednisolone, dipyridamole and fresh frozen plasma, the patient died six days later. Postmortem examination disclosed multiple microthrombi in the liver, kidney and pancreas. It was presumed that MMC had caused the illness. PMID- 1519931 TI - [A case report of metastatic colonic carcinoma in the liver effectively treated by long-term, ambulatory and continuous, intra-hepatic-arterial infusion of 5 fluorouracil using disposable multi-day-type infusor]. AB - A 42-year-old female was diagnosed as having sigmoid colonic carcinoma with multiple metastases in the liver. Following sigmoid colectomy and descending colostomy, a catheter was inserted from the right gastroepiploic artery to the proper hepatic artery. From the day of surgery 5-Fluorouracil was administered in doses of 250 mg/day continuously through a catheter over the 2-month period of hospitalization. After the patient was discharged, 250 mg/day of 5-Fluorouracil was administered at home using Vaxter Infusor according to a regimen of 10-day continuous infusion and subsequent 4-day rest. Five months after the initial operation, the serum CEA level decreased dramatically, and CT scan of the liver revealed the complete disappearance of the metastases. The patient underwent a second operation in which the colostomy was closed, and she is doing well at this writing. This case suggests that long-term, ambulatory, continuous and intra hepatic-arterial infusion of 5-Fluorouracil can be a very effective treatment not only in reducing the hepatic metastases but also in improving the quality of life of patients with colonic carcinoma. PMID- 1519932 TI - [Cell culture and its application current methods for a synchronous culture of mammalian cells]. AB - Synchronization of cells to various phases of the cell cycle in mammalian cells is crucial to analyze cell cycle progression and many other cellular functions. To date, various methods have been developed, such as mitotic selection, use of cell-cycle mutants, use of drugs which inhibit DNA replication (nucleoside analogue, excess thymidine, hydroxyurea, and aphidicolin), elutriation, deprivation of nutrients (amino acid, and serum), and new promising drugs of protein kinase inhibitors. Although above methods have both advantage and disadvantage, a practical and satisfactory method can be chosen from these method if taking into account goals of experiments and cell types to use. In near future, more powerful and reliable ones will be discovered since our understanding of the cell cycle has been increasing quite abruptly. PMID- 1519933 TI - Successful treatment of porokeratosis of Mibelli with diamond fraise dermabrasion. PMID- 1519934 TI - Benign pigmented nevi in children. Prevalence and associated factors: the West Midlands, United Kingdom Mole Study. AB - BACKGROUND AND METHODS: Prevalence of benign melanocytic nevi (moles) has been shown to be a major predictor of malignant melanoma. In this study the prevalence of moles in a group of 2140 children, aged 4 to 11 years, was determined. A standard questionnaire was completed by the parents of each child and included information on environmental and life-style factors. Examination data for each child were linked to the data obtained from the questionnaire. RESULTS: Prevalence increases rapidly throughout childhood and studies of children may indicate which factors contribute to mole development. Boys had more moles than girls, as did white children when compared with other ethnic groups. Prevalence of moles increased with age in children of both sexes. Among whites, skin color had little influence on mole prevalence. The following characteristics, however, were associated with an increased prevalence of moles: a propensity to burn rather than tan, a history of sunburn, a tendency to freckle, and a life-style involving increased sun exposure. A striking positive association between prevalence of moles and number of foreign holidays in a hot climate was observed. This association was independent of a history of sunburn. CONCLUSIONS: The study supports the hypothesis that environmental factors influence the prevalence of moles in childhood. PMID- 1519935 TI - Histologic and immunohistochemical study comparing xanthoma disseminatum and histiocytosis X. AB - BACKGROUND AND DESIGN: As xanthoma disseminatum and histiocytosis X share clinicopathologic features, difficulties in diagnosis can arise. The use of immunocytochemical markers for S100 protein, factor XIIIa, lysozyme, alpha 1 antitrypsin, for adherence of peanut agglutinin and of antibodies LN3 (HLA-DR), Leu-M1 (CD15), QBEnd/10 (CD34), MAC 387, and KP1 (CD68) as an aid to conventional histology has been studied in routinely fixed skin biopsy specimens from seven patients with xanthoma disseminatum and 12 patients with histiocytosis X. RESULTS: Typically xanthoma disseminatum occurs in discrete foci below an intact epidermis with individual cells set within a delicate fibrillary connective tissue stroma. In contrast, histiocytosis X usually occurs as a diffuse lichenoid infiltrate that can extend to deeper tissues. Epidermal invasion is common and the cells tend to lie free separated by edema fluid. Characteristic histiocytosis X cells are ovoid with an indented or kidney-shaped nucleus that occupies half or more of the cell. Xanthoma disseminatum cells differ in showing irregular scalloped borders, a more extensive cytoplasm, and an ovoid vesicular nucleus. Most xanthoma disseminatum cells labeled strongly for factor XIIIa and with KP1; a few cells labeled only weakly with peanut agglutinin. In contrast, most histiocytosis X cells labeled for S100 protein and with LN3 and peanut agglutinin. All the other markers remained negative in both conditions and were thus noncontributory for differentiating xanthoma disseminatum from histiocytosis X. CONCLUSIONS: We conclude that the differences in labeling patterns are a useful aid to histologic diagnosis of histiocytosis X and xanthoma disseminatum and they also reflect their separate histiogenesis. PMID- 1519936 TI - Peroxisomal abnormality in fibroblasts from involved skin of CHILD syndrome. Case study and review of peroxisomal disorders in relation to skin disease. AB - BACKGROUND AND DESIGN: Peroxisomal deficiency has been described in a number of syndromes characterized by chondrodysplasia punctata, including the Conradi Hunermann (C-H) syndrome. Because of overlapping clinical features of X chromosome inheritance, ichthyosis, and limb-reduction defects in C-H and CHILD (congenital hemidysplasia with ichthyosiform erythroderma and limb defects) syndromes, we examined peroxisomal content using diaminobenzidine cytochemistry and peroxisomal functions in fibroblasts from involved vs uninvolved skin of CHILD syndrome. RESULTS: Fibroblasts from involved skin of a patient with CHILD syndrome accumulated cytoplasmic lipid, visualized with the fluorescent probe, nile-red. Ultrastructurally, fibroblasts of involved skin of CHILD syndrome accumulated lamellated membrane and vacuolar structures. By diaminobenzidine ultracytochemistry, fewer peroxisomes were present. Moreover, the activities of two peroxisomal enzymes, catalase and dihydroxyacetone phosphate acyltransferase, were decreased (approximately 30% of normal). However, peroxisomal oxidation of very-long-chain and branched-chain fatty acids was preserved. Moreover, plasma very-long-chain fatty acids, plasma phytanic acid, and erythrocyte plasmalogen content were normal. CONCLUSIONS: The CHILD, C-H, and rhizomelic chondrodysplasia punctata syndromes are all characterized by ichthyosis, chondrodysplasia punctata, and limb defects, as well as peroxisomal deficiency. Thus, these syndromes may be related pathogenically. Because peroxisomes are involved in prostaglandin metabolism, peroxisomal deficiency may directly contribute to the previously reported alterations in prostaglandin metabolism in fibroblasts of involved skin of fibroblasts. PMID- 1519937 TI - Primary cutaneous aspergillosis near central venous catheters in patients with the acquired immunodeficiency syndrome. AB - BACKGROUND: Aspergillosis in patients with the acquired immunodeficiency syndrome is unusual, and the clinicopathologic features of primary cutaneous aspergillosis in this setting are undefined. Our findings show that the manifestations can differ from those of primary cutaneous aspergillosis in other immunocompromised patients. OBSERVATIONS: Two men with the acquired immunodeficiency syndrome developed foci of primary cutaneous aspergillosis beneath adhesive tape near central venous catheter sites. Typical lesions were flesh-colored to pink, umbilicated papules that clinically resembled molluscum contagiosum. Biopsy specimens showed variably ruptured follicles that contained collections of fungal hyphae typical of Aspergillus species. Cultures in one case identified Aspergillus fumigatus. The use of nonocclusive dressings and local wound care resulted in involution of several lesions. CONCLUSIONS: Primary cutaneous aspergillosis begins as saprophytic involvement of hair follicles secondary to the altered microenvironment beneath adhesive tape. Systemic antifungal therapy is prudent, but in the absence of neutropenia or other traditional risk factors for dissemination, it appears that Aspergillus in patients with the acquired immunodeficiency syndrome can produce relatively indolent cutaneous lesions with a tendency to resolve once precipitating factors are removed. PMID- 1519938 TI - Xeroderma pigmentosum variant with multisystem involvement. AB - BACKGROUND: Xeroderma pigmentosum (XP) is a hereditary disorder characterized by recessive inheritance and elevated rates of skin carcinogenesis. There are seven complementation groups (A through G) for which the genetic defect results in a failure to repair DNA damage from UV light and sunlight; one group, the variant, fails to replicate UV-damaged DNA correctly. Patients in XP groups A, B, D, and G have associated neurologic problems, the most severe being known as the DeSanctis Cacchione syndrome. OBSERVATIONS: We describe a patient with XP from consanguineous parents who has severe multisystem involvement similar to that of the DeSanctis-Cacchione syndrome. Extensive laboratory investigation showed that cells from this patient exhibit DNA replication after irradiation with UV light that is characteristic of the XP variant. The cells also show normal sensitivity to UV light and normal excision repair, consistent with XP variant classification. The presence of the neurologic symptoms is quite unusual in an XP variant. CONCLUSION: Our patient clearly fits into the XP variant category based on normal survival, caffeine toxic reaction, photoproduct excision and repair, and the deficient replication of UV-damaged DNA. This patient seems to be rare, however, among XP variants in displaying severe neurologic symptoms. Because of the consanguineous parents, the possibility that some of this patient's findings are from non-XP-related abnormalities must also be entertained. However, other consanguineous patients with XP variant, eg, XPIOCA, have been described who do not show neurologic abnormalities. In view of the difficulty of defining an XP group from clinical symptoms alone, we urge the term xeroderma pigmentosum variant be used only in the context of the laboratory studies of patients with XP that contain normal repair but deficient semiconservative replication of UV damaged DNA. PMID- 1519939 TI - Possible Werner syndrome. A unique association with spontaneous digital gangrene in infancy and decreased life span of cultured skin fibroblasts. AB - BACKGROUND: Werner syndrome is a hereditary disease characterized by several features generally associated with aging. However, the differences between Werner syndrome and the normal aging process are clear. Werner syndrome is usually diagnosed through the clinical signs and symptoms it presents. In recent years, however, the cultured skin fibroblasts of patients have grown slowly and patients have a short life span; these characteristics provide a useful diagnostic aid. OBSERVATIONS: We recently examined a 42-year-old single man who had short fingers, marked facial scars resulting from chilblain-like eruption in infancy, glaucoma caused by uveitis developed in his middle age, callosities on the soles, and immaturation of sexual glands. Repeated peripheral blood examinations showed a positive result for antinuclear factor, slight elevation of immunoglobulin levels, and a low leukocyte count. His family had repeated consanguineous marriages and his parents were cousins. We cultured skin fibroblasts from the patient's forearm and compared them with those of four normal control male subjects. The patient's skin fibroblasts showed a remarkably low population growth rate and a total replicative life span. CONCLUSION: The patients presented unique clinical features for Werner syndrome such as chilblain-like eruption in infancy and glaucoma caused by uveitis. Cell culture studies revealed cellular abnormalities compatible with Werner syndrome. We thus diagnosed the patients as possibly having Werner syndrome. PMID- 1519940 TI - Congenital erythropoietic porphyria. A mild variant with low uroporphyrin I levels due to a missense mutation (A66V) encoding residual uroporphyrinogen III synthase activity. AB - BACKGROUND AND DESIGN: Congenital erythropoietic porphyria, an inborn error of heme biosynthesis, results from the deficient activity of the enzyme uroporphyrinogen III synthase. The clinical manifestations in unrelated patients with this autosomal recessive disorder are remarkedly variable, ranging from mild cutaneous involvement to severe transfusion-dependent hemolytic anemia. Biochemical and molecular studies were undertaken to investigate the nature of the unusually mild phenotype in a 15-year-old boy with only cutaneous manifestations. RESULTS: The proband's levels of total porphyrins, urinary uroporphyrin I, and erythrocyte coproporphyrin I were elevated, but not as dramatically as in other patients with this porphyria. Interestingly, the erythrocyte uroporphyrinogen III synthase activity in the proband was about 21% of the normal mean, indicating the presence of significant residual activity. In cultured lymphoblasts from the proband, his father, and mother, the enzymatic activities were 10%, 70%, and 50% of the normal mean, respectively. Molecular analyses revealed that the proband was heteroallelic for two uroporphyrinogen III synthase missense mutations: the C73R allele inherited from his mother and the A66V allele transmitted by his father. The A66V allele encoded residual enzymatic activity in vitro while the C73R allele did not. CONCLUSIONS: The A66V allele accounted for the proband's low levels of porphyrin accumulation and mild clinical manifestations. Such genotype-phenotype correlations should provide understanding of the remarkable clinical variability in other patients with this inherited porphyria. PMID- 1519941 TI - Information excess in medicine. Overview, relevance to dermatology, and strategies for coping. AB - BACKGROUND: The amount of biomedical information contained in scientific journals has grown to the point that complete coverage of this material is impossible. The number of articles and journals being published has been growing at an exponential rate since 1750. Thirty-four thousand references from 4000 journals are added each month to the National Library of Medicine MEDLINE database from among the more than 100,000 scientific journals now published. This increase in scientific literature reflects not greater productivity but simply a larger number of scientists at work. Most articles written are eventually published in the medical literature, but a large number of scientific articles are of less than optimal quality, and most scientific articles that are published are never cited. Articles of higher quality and usefulness cluster in a few journals that enjoy great use in medical libraries and high scores on bibliometric scores such as the Science Citation Index. OBSERVATIONS: To assess the reading habits of dermatologic trainees and evaluate how they cope with this information excess, a survey was distributed to 36 residents in three training programs. The average number of medical journal reading hours per month was 17; the number of hours devoted to reading issues of the Archives of Dermatology, the Journal of the American Academy of Dermatology, and the Journal of Investigative Dermatology were 3.2, 5.0, and 1.4, respectively; and the average resident read seven peer reviewed journals, two to four dermatologic tabloids, and four peer-reviewed medical journals. CONCLUSIONS: Critically and consistently reading a limited number of high-quality peer-reviewed journals as well as taking advantage of information available through computer networks and bibliographic and full-text databases is the best approach to coping with the volume of medical literature. Translating this information into a change in attitude and modification of physician behavior is best accomplished when local role models incorporate new ideas into their practice and teaching. Modifications that would, in fact, bring about truly useful changes, such as decreasing the number of new publications, melding journals already present into smaller numbers of publications rather than instituting new journals, altering the "publish-or-perish" rules, and writing more comprehensive articles rather than multiple small contributions, all await fundamental alterations in long-accepted policies in medicine. PMID- 1519942 TI - Scabies in chronic health care institutions. AB - BACKGROUND: The diagnosis and management of outbreaks of scabies in health care facilities may be difficult. As there is little information available regarding the extent of this problem we conducted a questionnaire study to provide an indication of the occurrence of scabies in chronic health care facilities in the province of Ontario, Canada. It also documented the facilities' approach to the management of the disease. OBSERVATIONS: Two outbreaks of scabies in chronic health care facilities are described. The questionnaire study revealed that 25% of the institutions reported that they had problems with scabies over a 1-year period. A minority had a written policy with respect to dealing with the management of scabies, particularly in the setting of a mass outbreak. CONCLUSIONS: Scabies is a common problem in chronic health care facilities; however, diagnosis and management may be difficult. The development of a specific protocol for the management of such outbreaks by the appropriate public health agencies would be useful. PMID- 1519943 TI - Figurate erythema, photosensitivity, and conjunctival irritation of recent onset. Subacute cutaneous lupus erythematosus (SCLE) and keratoconjunctivitis sicca. PMID- 1519944 TI - A bullous eruption in a young woman. Bullous pemphigoid (BP). PMID- 1519945 TI - Hypopigmented macules. Hypopigmented mycosis fungoides (MF). PMID- 1519946 TI - Umbilical mass. Omphalith. PMID- 1519947 TI - Diaper dermatitis and perianal pseudoverrucous papules. PMID- 1519948 TI - Severe phototoxic burn following celery ingestion. PMID- 1519949 TI - The accuracy of dermatologists in the diagnosis of melanoma. PMID- 1519950 TI - The clinical spectrum from classic varicella zoster to zoster sine herpete: the missing link. PMID- 1519951 TI - Application of glacial acetic acid to penile skin. PMID- 1519952 TI - Topical cyclosporine in the treatment of vulvar lichen sclerosus: clinical, histologic, and immunohistochemical findings. PMID- 1519953 TI - Angelman's syndrome. PMID- 1519954 TI - Psychological treatments for childhood asthma. PMID- 1519955 TI - Birth weight and hospital admission before the age of 2 years. AB - Admission rates to hospital of children born weighing 1500 g or less were compared with those born with birth weights over 1500 g in a retrospective analysis of routinely collected data from the Oxford Record Linkage Study. The children were born in the three five year periods 1968-72, 1974-8, and 1979-83 to women resident in Oxfordshire and West Berkshire. The main measures of the study were survival rates to 28 days after birth and hospital admissions of survivors up to the age of two years. Among babies weighing 1500 g or less, neonatal survival rates rose from 350.2 per 1000 total births in 1968-72 to 577.4 per 1000 among births in 1979-83. Over the same period, the proportion of children admitted to hospital at least once before the age of 2 years rose from 218.6 per 1000 survivors to 444.4 per 1000. In the children with birth weights over 1500 g, survival rates rose from 985.5 to 995.9 per 1000 births and hospital admission rates rose from 98.2 to 144.4 per 1000 survivors over the same time period. Although very low birthweight children did not contribute significantly to total hospital bed occupancy, because their numbers were small in relation to the total number of children in the population, their contribution increased between the five year periods 1968-72 and 1979-83. It should therefore be continuously monitored using routine systems. PMID- 1519956 TI - Suspected child abuse: cost in medical time and finance. AB - In a prospective study the number of children attending the Royal Liverpool Children's Hospital (RLCH) for examination after allegations of child abuse, and the type of abuse involved, was recorded from July to December 1990. The cost to the hospital of these examinations and initial investigations was assessed. The study was carried out in the major and minor accident and emergency departments and the Rainbow Centre of the RLCH. In six months 181 children were examined. Cases of sexual abuse and non-accidental injury were seen in equal numbers. Girls outnumbered boys and 60% were referred by social services. The costs over the six month period were 31,739 pounds. The minimum projected annual cost is 63,500 pounds. We conclude that the cost of running an effective service for the initial assessment of children who are possible victims of child abuse is considerable in practical terms and in medical time. PMID- 1519957 TI - Screening of hearing impairment in the newborn using the auditory response cradle. AB - The Auditory Response Cradle (ARC) is a fully automated microprocessor controlled machine that was designed for the hearing screening of full term neonates. In order to evaluate the ARC, 6000 babies were screened at a district maternity hospital over a period of three years. Every infant subsequently entered a three year follow up programme. One hundred and two babies (1.7%) failed the ARC screen (that is, they failed two ARC tests) and 20 of these were found to have some hearing impairment: in 10 it was severe (80-90 dBHL), in seven moderate (45-60 dBHL), and in three it was mild to moderate (less than 45 dBHL). In addition, of the 20 babies who failed a first test and were discharged before a second could be performed, two were confirmed to have a severe hearing loss; 79 infants failing the screen were cleared on further testing, giving the ARC a false positive rate of 1.3%. On following up all 6000 infants for three years, seven children who passed the neonatal screen were subsequently found to have a hearing loss. For two babies the aetiology was unknown but for five the hearing impairment was either due to a hereditary progressive loss or definite postnatal factors. Progressive and acquired hearing losses cannot be detected at a neonatal screen and this emphasises the need for follow up screens at other stages in the child's life. In this long term study the ARC has been found to have a high detection rate for severe hearing loss and confirms the practical possibility of using a behavioural technique for the universal screening of hearing in neonates. PMID- 1519959 TI - Sequelae of haemolytic uraemic syndrome. AB - Twenty two patients with previous episodes of haemolytic uraemic syndrome (HUS) were investigated for evidence of deficits in cognitive, behavioural, and academic function. Patients were pair matched with 22 controls for age (+/- 1 year), gender, and socioeconomic status. HUS patients had numerically lower cognitive and achievement scores and higher behavioural problem ratings than their controls on every measure. None of the group differences was significant at the 0.01 level. Significance values between 0.10 and 0.01 were obtained for the Wechsler full scale and verbal intelligence quotient scores and for several of the achievement measures and behaviour ratings. These results were conservatively interpreted as trends and are considered to provide preliminary indications of a post-HUS deficit in behaviour, verbal intelligence, and the verbally based skills of reading comprehension and vocabulary. The findings provide interim guidelines for follow up care but require confirmation and elaboration in a larger study. PMID- 1519958 TI - Growth of infants with neonatal growth hormone deficiency. AB - In view of contradictory reports on the growth hormone dependency of early postnatal growth we studied the growth curves of 15 infants with neonatal growth hormone deficiency. In seven infants the growth curve was parallel to the standards of the infancy-childhood-puberty (ICP) model (group 1), but in the remaining infants there was an immediate deviation of the growth curve (group 2). In this group the mean (SD) at 4 and 9 months of age was -3.3 (1.1) and -4.9 (1.4), respectively, when compared with the ICP model. The mean birth length in both groups was decreased and five out of 15 had a birth length of less than -2 SD. Serial measurements of the growth hormone response to provocation tests in two patients in group 2 showed decreasing concentrations, while four patients with documented complete growth hormone deficiency belonged to group 2. We conclude that growth hormone is needed for early infant growth and that the normal growth pattern in some infants with neonatal pituitary dysfunction is due to incomplete insufficiency. PMID- 1519960 TI - Randomised trial of a ready-to-feed compared with powdered formula. AB - Forty three infants were assigned randomly to a ready-to-feed infant formula or a standard formula that required reconstitution from powder. Despite similar nutrient composition of the two formulas those fed the powdered formula had significantly increased body weight and skinfold thickness gains, and became significantly heavier than a further group of 20 breast fed infants by 3 and 6 months. Of those fed the powdered formula 6/19 had become overweight (above the 90th or 97th centile) by 6 months, whereas 1/19 fed the ready-to-feed product was overweight at this age. While differences in fat absorption might have been contributory, our data suggest that errors in reconstitution of formula from powder might be the main cause for the growth differences observed. If it is appropriate to take the breast fed infant as a model, infants fed ready-to-feed formula in this study showed a more physiological pattern of growth than those fed a standard formula reconstituted from powder. These results require replication using other formulas as the findings have potentially important implications for infant feeding. PMID- 1519961 TI - Management and response to treatment of Helicobacter pylori gastritis. AB - Gastritis associated with Helicobacter pylori was present in gastric biopsies from 24/95 (25%) children and adolescents undergoing endoscopy for recurrent abdominal pain and upper gastrointestinal symptoms. H pylori associated gastritis occurred mainly in older children (8-16 years) and was significantly associated with low socioeconomic class and a family history of peptic ulcer disease. Antral nodularity was a common endoscopic finding in H pylori positive children. Eighteen children, all over 5 years of age, were treated with tripotassium dicitratobismuthate (De-Nol) for two months and ampicillin for two weeks. In 12 children follow up gastric biopsies were obtained six weeks after completion of treatment. In 9/12 (75%) children H pylori was eradicated, and gastritis improved. PMID- 1519962 TI - Positive rolandic sharp waves in the EEG of the premature newborn: a five year prospective study. AB - In a prospective study of 301 premature newborn infants, neonatal tracings were done to evaluate the use of the electroencephalogram (EEG) and positive rolandic sharp waves (PRSW) in the diagnosis and prognosis of periventricular leucomalacia. Each infant had ultrasonographic studies and standardised neurological examinations at 1 year of age or later. Two hundred and eighty infants were followed up at 1 year. This study demonstrated that the absence of PRSW was correlated with a favourable motor development (98.2%) and confirmed the great value of PRSW in the diagnosis and the prognosis of periventricular leucomalacia. PRSW were sensitive (98%) and specific (84%) markers of developmental motor disability and were a sensitive (96%) marker of severe spastic diplegia. A frequency above 2/minute was a specific (92%) sign of severe spastic diplegia. Social and language developmental abnormalities were not correlated with the neonatal EEG. PMID- 1519963 TI - Occurrence of suppurative lymphadenitis after a change of BCG vaccine. AB - BCG vaccines are the oldest vaccines in use today, but the protective effect of the vaccination is still controversial. The risk of contracting tuberculosis is low compared with the possible complications after this vaccination. In Austria the formerly used BCG vaccine was not available in the required amount and another vaccine was released by the drug authorities. This product, with a more virulent strain, was used between August and December 1990, and this increased the incidence of complications. Eighty four of 1950 vaccinated newborn babies developed severe suppurative lymphadenitis three to 28 weeks after the vaccination, and surgical treatment was found to be necessary. Isoniazid treatment did not prove to be successful when the lymph node exceeded a certain size. Culture was successful in 46% up to week 20; after 20 weeks no culture became positive. All cultured bacteria were isoniazid sensitive. The question of general vaccination is raised and several points were considered before we came to the conclusion that except for high risk groups a general vaccination programme for neonates is not justified in Western countries. PMID- 1519964 TI - Necrobacillosis with pancytopenia. AB - Two young children whose presentation with necrobacillosis caused considerable diagnostic difficulty resulting in referral to an oncology unit are described. In both cases their severe suppurative multisystem illness was complicated by pancytopenia. One had bone marrow infarcts and severe endocarditis in addition to pulmonary involvement and the other had osteitis which resulted in a deformed humerus. PMID- 1519965 TI - Protein S deficiency: early presentation and pulmonary hypertension. AB - Protein S deficiency usually presents in adults with recurrent or unexplained thrombosis and is thought to have autosomal dominant inheritance. We describe the case of a 5 year old girl with pulmonary hypertension but no evidence of venous thrombosis until postmortem examination. Her parents were first cousins. This potentially treatable condition should be sought in children and their relatives screened. PMID- 1519967 TI - Psychiatric treatment for children--the organisation of services. PMID- 1519966 TI - Myelodysplastic syndromes. PMID- 1519968 TI - Recent progress in intestinal transplantation. PMID- 1519969 TI - Diazoxide--an orphan drug? PMID- 1519970 TI - Prostacyclin concentrations in haemolytic uraemic syndrome after acute shigellosis. PMID- 1519971 TI - Do we need an Apgar score? PMID- 1519972 TI - Metabolic acidosis in newborn infants. PMID- 1519973 TI - Fetal abnormality: an audit of its recognition and management. Northern Regional Survey Steering Group. AB - A voluntary survey set up by local clinicians has documented all lethal abnormality in a geographically defined area of northern England where there were 361,037 registered births between 1982 and 1990, and monitored the incidence of all significant physical abnormality since January 1984. The survey aims to maintain a register of all pregnancies where an abnormality is suspected before birth, and those where an abnormality is only identified after birth, together with a record of how the diagnosis was established. Information on management and outcome a year after birth is also collected. Nearly half the total decline in perinatal mortality in the region between 1982 and 1990 is accounted for by an increase in the antenatal recognition of lethal abnormality, isolated hydrocephalus, or a neural tube defect and subsequent termination of pregnancy. Although the reporting of many non-lethal conditions was incomplete during the pilot study in 1984, it has become progressively more complete since then. The number of cases confirmed postnatally varied little between units between 1985-9, but audit showed that the proportion recognised antenatally varied fivefold for reasons unconnected with unit size or the amount of antenatal ultrasound work done. For a number of serious conditions more than 10% of all antenatal diagnoses were completely wrong. Survey data are, for the first time, making it possible to monitor the accuracy of the ultrasound-based screening and diagnostic services for identifying specific fetal abnormalities. They are also providing clinicians with an invaluable confidential database of a whole region's collective experience of dealing with complex fetal abnormality. PMID- 1519974 TI - Potential impact of population screening for prenatal diagnosis of congenital heart disease. AB - The potential impact of prenatal screening for the detection of congenital heart disease (CHD) was assessed by prospective analysis of 428 consecutive infant admissions to a supraregional centre; 28 (6.5%) did not have CHD and were excluded from analysis. Of the 400 cases with CDH, 396 (99%) underwent fetal ultrasonography but scanning was performed only before 18 weeks' gestation in 200 (50%). One hundred and forty nine (37%) of all cardiac abnormalities and 149/283 (53%) of severe abnormalities were considered to be detectable prenatally in a screening echocardiographic four chamber view had this technique been used. Prenatal diagnosis of severe CHD actually occurred in only eight (2%) cases and was after 30 weeks' gestation in all. There were 181/347 (52%) of all mothers and 177/253 (70%) of the subgroup with severe abnormalities who expressed an opinion volunteered their preference for termination of pregnancy if mid-trimester diagnosis had been available. Mid-trimester detection of congenital heart disease rarely occurs at present despite fetal ultrasound scanning in almost all pregnancies. More than half of all severe congenital heart defects seen in infancy are potentially detectable by screening. Major training at primary scan level and modification of the timing of existing fetal anomaly scanning would be required for a screening programme to be effective. PMID- 1519975 TI - Skin temperature and heart rate rhythms in infants of extreme prematurity. AB - Nine preterm infants of 26 to 29 weeks' gestational age and 792 to 1200 g birth weight spent six to 17 weeks in our neonatal medical unit. Hourly recordings of skin temperature and heart rate were carried out. The first five to 15 weeks were spent in the intensive care ward, in continuous light, due to various medical conditions. After recovery they were moved to a nursery for one to nine weeks, with 12 hourly periods of light and darkness. Four infants developed circadian rhythms in temperature and three in heart rate in light-dark periods, the remainder failing to do so. Some infants take longer than others to develop circadian rhythms but the reasons for this are not clear. It is suggested that earlier exposure to a light-dark environment may synchronize the 'body clock' to a 24 hour period in more preterm infants. PMID- 1519976 TI - Prediction of impaired metabolic adaptation by antenatal Doppler studies in small for gestational age fetuses. AB - The increased risk of hypoglycaemia for infants who are small for gestational age (SGA) is well known, and further information regarding metabolic adaptation can be gained by examining the profiles of glucose and other metabolic fuels in such infants. Not all SGA infants experience hypoglycaemia, however, and the ability to identify, antenatally, those at most risk would be helpful for obstetric and neonatal management. This study investigated metabolic differences between two groups of SGA infants who had antenatal umbilical artery Doppler studies. Fourteen had end diastolic velocities (EDV) present and 11 had absent EDV. The absent EDV group had significantly lower non-esterified fatty acid (NEFA) concentrations at birth, and lower blood glucose and NEFA concentrations in the first six hours after birth. After the first day, few metabolic differences were found between the two groups. Antenatal Doppler studies may identify those SGA infants who fail to achieve neonatal metabolic adaptation and are most at risk of early neonatal hypoglycaemia. PMID- 1519977 TI - Superior mesenteric artery blood flow velocity in necrotising enterocolitis. AB - Doppler measurements of blood flow velocity were obtained from the superior mesenteric artery (SMA), coeliac axis, and anterior cerebral artery (ACA) of 19 infants with suspected necrotising enterocolitis, which was classified as confirmed (n = 9) or unconfirmed (n = 8). Infants with confirmed disease were compared with controls who were either enterally fed or who were receiving intravenous fluids. SMA velocity was significantly higher in the infants with confirmed necrotising enterocolitis (36.5 cm/s) than in unfed controls (20.4 cm/s) or infants with unconfirmed enterocolitis (19.6 cm/s). Three infants with confirmed disease had data from before the onset of symptoms. One had low SMA velocity on the first day of life, and one showed no increase in SMA velocity after enteral feeds were started. SMA velocity is increased when infants develop symptoms of necrotising enterocolitis, suggesting that total gut ischaemia is not present at the time that the disease is clinically apparent, although it may precede the onset of symptoms and play a part in the pathogenesis of the disorder. PMID- 1519978 TI - Development of cutaneous microflora in premature neonates. AB - Coagulase-negative staphylococci (C-NS) are a frequent cause of bacteraemia in premature neonates. It is likely that the strains of C-NS causing bacterial sepsis in premature neonates have their origin on the patient's skin surface. We have studied the quantitative development of the skin microflora at eight sites on premature neonates. A swab wash method was used to sample and enumerate the cutaneous microflora of premature neonates admitted to an intensive care unit with respiratory distress syndrome. The numbers of bacteria present on the skin increased rapidly by 100-fold in the first week of life. The species of C-NS found on neonatal skin were similar to those found on adult skin. However, the bacterial population was 10(3) lower by comparison. There was considerable variation in numbers of bacteria and in the proportion resistant to antibiotics from day to day. There appeared to be no association between antibiotic usage and the proportion of isolates resistant to antibiotics, although the resident bacteria were in many cases resistant to a variety of antibiotics. C-NS were isolated from 92% of samples from which bacteria were isolated. Staphylococcus epidermidis was found at all sites and accounted for 82% of each colonial type of staphylococcus isolated. Other organisms isolated included Propionibacterium sp, alpha-haemolytic streptococci, aerobic spore-bearing bacilli, aerobic coryneforms, Candida albicans, Klebsiella oxytoca, Pityrosporum sp, Klebsiella pneumoniae, and Escherichia coli. The results of this study suggest that the skin of premature neonates is colonised with antibiotic resistant C-NS during the first week of life and that the chance of contamination of an intravascular catheter at insertion increases during this period. PMID- 1519979 TI - Complement activation in neonatal infection. AB - To investigate the usefulness of indices of complement activation in the diagnosis of infections in the neonatal period, activation products C4d, Ba, and C3d were measured in 42 babies with a putative diagnosis of infection based on clinical/laboratory criteria, and compared with conventional clinical and haematological criteria of infection and with C reactive protein. The diagnosis of sepsis was confirmed by culture and identification of organisms in 17. Fourteen babies in whom infection was not suspected formed the control group. In babies with proved infection, concentrations of the fragments C4d, Ba, and C3d were higher than in babies with suspected infection in whom microbiological tests were negative, and concentrations of Ba and C3d were higher than in controls. C reactive protein and the platelet count were not significantly different in babies with proved infection and those with negative microbiological tests, but in the latter, C reactive protein concentrations were higher than in controls. Of the indices studied, high concentrations of Ba predicted microbiologically proved infection with the highest sensitivity (47.1%) and specificity (92.0%). Ba thus seems to be useful as an early indicator of infection in the neonatal period. PMID- 1519980 TI - Receiver operating characteristic curves for comparison of serial neutrophil band forms and C reactive protein in neonates at risk of infection. AB - The performance of indirect indices of infection in the newborn vary because of differences in techniques, including diagnostic cut off levels. We have compared serial neutrophil band cell counts with C reactive protein measured by rate nephelometry. The 'gold standard' was a positive culture and the performance of the tests was compared by the technique of receiver operating characteristics (ROC) as well as sensitivity and specificity. A total of 172 septic screens were performed in 56 patients. The operational diagnostic cut off values were: C reactive protein greater than 8 mg/l, immature:total neutrophil ratio (I:T ratio) greater than 0.2, and band count greater than 5%. Compared with the sensitivity of C reactive protein (71%), I:T ratio (34%) was significantly different but band count (69%) was not. The specificity of C reactive protein (72%) was better than band count (39%) but no better than I:T ratio (73%). ROC curves were constructed for all possible diagnostic cut off values of the tests and superior performance was demonstrated for C reactive protein compared with band count and I:T ratio. We conclude that C reactive protein is a useful early indicator of infection in neonates and that ROC curves permit comprehensive and graphic comparison between tests and the calculation of optimal diagnostic cut off values. PMID- 1519981 TI - Neutrophil chemotaxis and adhesion in preterm babies. AB - To investigate the increased susceptibility to infection of very immature preterm neonates, neutrophil chemotaxis, Mac-1 adhesion receptor expression, and adherence to human umbilical vein endothelial cell monolayers (HUVE) were examined in neonates born at less than or equal to 32 weeks' gestation. Chemotaxis of neutrophils from well preterm neonates towards casein or zymosan activated serum (ZAS) was reduced (mean SE) being for casein 88.6 (3.8) microns; ZAS 76.2 (4.3) microns compared with adults (casein 117.8 (1.4) microns; ZAS 112.1 (1.4) microns), but similar to term neonate neutrophils (casein 92.7 (4.5) microns; ZAS 75.9 (3.1) microns). Stimulated Mac-1 expression showed a similar pattern: reduced on preterm neutrophils compared with adults, but similar to term neonates. Preterm and term neonate neutrophils were both hyperadherent to HUVE when unstimulated, but showed an equally impaired ability to increase adhesion following stimulation. Casein stimulated chemotaxis and stimulated Mac-1 expression 'matured' towards adult levels of performance four weeks after preterm birth. The increased incidence of sepsis in immature preterm infants is not due to greater defects of neutrophil migration. PMID- 1519982 TI - Serum erythropoietin concentrations in symptomatic infants during the anaemia of prematurity. AB - A comparison was carried out between a series of neonates who weighed less than 1500 g at birth and received red cell transfusions for symptomatic anaemia of prematurity (group 1, n = 14) and controls of similar gestational age and weight, who remained well and were not transfused during their nursery stay (group 2, n = 10). Mean (SD) haemoglobin concentrations at birth were 163 (12) g/l and 183 (17) g/l (p = 0.004), respectively. Transfusion resulted in significantly better weight gain in six infants who had been growing poorly:mean (SE) 8.8 (2.8) g/day improved to 23.3 (2.1) g/day (p less than 0.002). Geometric mean (SD) serum immunoreactive erythropoietin (SiEp) concentrations (17.7 (1.3) U/l) for the whole group of infants were similar to those of normal adults (17.4 (4.7) U/l) despite considerably reduced haemoglobin values. There was a significant inverse correlation between haemoglobin and log SiEp concentrations in the infants requiring transfusion (r = -0.43; p less than 0.01), but this was not apparent in the untransfused babies. Moreover, at haemoglobin concentrations below 120 g/l the mean (SE) SiEp concentration of 20 (1.08) U/l in group 1 was significantly higher than in group 2 (14 (1.06) U/l; p = 0.002). These data suggest that an increased concentration of SiEp early in the course of the anaemia of prematurity helps to identify those infants who would benefit from red cell transfusions, but that clinical criteria, although ill defined, do so equally well. PMID- 1519983 TI - UK experience in neonatal extracorporeal membrane oxygenation. AB - Extracorporeal membrane oxygenation (ECMO) is a life support technique capable of supporting pulmonary, cardiac, or cardiopulmonary function. It has proved most successful in neonatal respiratory failure. We report the initial UK experience with a survival rate of 80% in 15 neonates (gestations 36-41 weeks, birth weights 2690-3990 g) whose condition exceeded American criteria for ECMO treatment for a prolonged period before referral. Ages at referral varied from 11 to 240 hours and the duration of bypass required varied from 30 to 240 hours respectively. PMID- 1519984 TI - Episodic bradycardia in preterm infants. AB - To analyse factors likely to precipitate bradycardia, 27 preterm infants born at 32 weeks' gestation or less were studied on 89 occasions. Polygraphic recordings of electrocardiography, oxygen saturation, and respiratory effort were made. Subsequently, upper airway flow was measured by a mask and pressure transducer. In 605 episodes detected during initial recordings, time of onset of bradycardia correlated positively with apnoea duration, with bradycardia often occurring as respiratory effort resumed. Airway closure occurred in 88% of apnoeas associated with bradycardia during flow measurements, and was significantly more common than in apnoea without bradycardia (64%). We suggest that bradycardia is most commonly a reflex response to the resumption of respiratory effort against a closed upper airway as apnoea is terminated, and that this reflex is potentiated by hypoxaemia. PMID- 1519985 TI - Cerebrovascular carbon dioxide reactivity and failure of autoregulation in preterm infants. AB - Changes in cerebral blood flow velocity (CBFV) in response to a rise in arterial carbon dioxide tension (PaCO2) in 94 ventilated preterm infants were determined using Doppler ultrasound to assess whether the nature of this change might predict subsequent neurological injury. Concomitant changes in mean arterial pressure (MAP) were recorded. Both CBFV and MAP rose significantly in response to the rise in PaCO2, the response being significantly less in the first 24 hours. Analysis indicated that the change in CBFV in the first day of life in infants less than or equal to 30 weeks' gestation was dependent to a great extent on the concomitant change in MAP. Similar dependence also occurred after administration of pancuronium to infants whose CBFV response was previously independent of changes in MAP. This dependency lasted for the duration of paralysis. Changes in CBFV after a rise in PaCO2 did not predict subsequent neurological injury. The influence of pancuronium on cerebrovascular regulation warrants further study. PMID- 1519986 TI - Traumatic neonatal intracranial bleeding and stroke. AB - Ischaemia within the regions supplied by vertebral and posterior cerebral arteries has been described as a complication of birth injury, either by direct trauma or by compression from a herniated temporal uncus. Ischaemia within the territory of the middle cerebral artery has been documented after a stretch injury of the vessel's elastica interna. From a series of seven personal observations on birth trauma and related cerebral stroke, we describe three neonates with the uncal herniation type of occipital stroke and four infants with hypoperfusion of the middle cerebral artery or one of its major branches. In three of the latter a basal convexity subdural haemorrhage probably induced the ischaemia, whereas in the other it was associated with haemorrhagic contusion of the parietal lobe. Experimental work and reports on older children support the idea that vasospasm due to surrounding extravasated blood can be one of the responsible mechanisms. Both forceps delivery and difficult vacuum extraction can be implicated in this supratentorial injury, leading to permanent neurological damage in at least half of the survivors in this series. PMID- 1519987 TI - Athetoid cerebral palsy with cysts in the putamen after hypoxic-ischaemic encephalopathy. AB - Three cases of athetoid cerebral palsy after hypoxic-ischaemic encephalopathy (HIE) are reported. All three neonates had haemorrhagic lesions in the basal ganglia and thalami on magnetic resonance imaging (MRI). Prior cranial ultrasound had detected the lesions in only two cases. In all three children athetoid movements began within the first year of life. Follow up MRI scans showed bilateral symmetrical cystic lesions in the posterior putamen. Although haemorrhagic lesions within the basal ganglia are a common MRI finding in neonates with HIE, few of these babies develop athetoid cerebral palsy. We believe this to be the first report of discrete cystic lesions found in the basal ganglia of children with athetoid cerebral palsy. PMID- 1519988 TI - Regional cerebral blood flow velocity changes after indomethacin infusion in preterm infants. AB - Cerebral blood flow velocity was assessed during infusion of indomethacin over 30 minutes. Eleven preterm infants with symptomatic patent ductus arteriosus were studied on 12 occasions. Indomethacin infusion was associated with a significant reduction in time averaged mean velocity (TAMV), peak systolic velocity (PSV), and end diastolic velocity in both the anterior cerebral artery and middle cerebral artery. The fall in the TAMV and PSV was gradual with maximal change 30 40 minutes after the start of the infusion. It was concluded that administration of indomethacin by slow infusion produces haemodynamic alterations to the cerebral circulation comparable in magnitude with changes described with bolus administration. Indomethacin remains a useful and effective treatment for patent ductus arteriosus in preterm infants, but should continue to be used with caution. PMID- 1519989 TI - Randomised trial of umbilical arterial catheter position: Doppler ultrasound findings. AB - Umbilical arterial catheters (UAC) were randomly assigned in 69 infants to a high (n = 36) or to a low (n = 33) position. Serial Doppler ultrasound measurements of blood flow velocity in their superior mesenteric arteries, coeliac axis, renal arteries, and anterior cerebral arteries were then obtained. There were no differences in blood flow velocity between high and low UAC groups on days 1, 3, and 7. At 2 weeks, those infants with a high UAC still in place had significantly higher velocities in the mesenteric artery than those infants who had no catheter in place. Infants with high UACs remaining in place for more than 7 days were found to have an increase in abdominal distension and tenderness, whereas this was not the case for those with low UACs. Catheter position has no effect on visceral blood flow if the UAC stays in place for one week or less, whereas prolonged use of a high UAC may alter intestinal blood flow and increase the incidence of abdominal symptoms. PMID- 1519990 TI - Screening for retinopathy of prematurity. PMID- 1519991 TI - Report of working group of the British Association of Perinatal Medicine and Neonatal Nurses Association on categories of babies requiring neonatal care. PMID- 1519992 TI - Mineral transport across the placenta. PMID- 1519993 TI - Putting the clock back 30 years: neonatal care since the 1991 NHS reforms. PMID- 1519994 TI - Dr Thomas Denman of London (1733-1815): rupture of the membranes and management of the cord. PMID- 1519995 TI - Aerosol drug delivery to intubated neonates. PMID- 1519996 TI - Catabolic effect of dexamethasone in the preterm baby. PMID- 1519997 TI - Respiratory support using patient triggered ventilation in the neonatal period. PMID- 1519998 TI - Premature labour. PMID- 1519999 TI - Low dose intraventricular fibrinolytic treatment to prevent posthaemorrhagic hydrocephalus. PMID- 1520000 TI - Rh haemolytic hepatitis. PMID- 1520001 TI - Cord blood lymphocyte responses to food antigens for the prediction of allergic disorders. AB - Proliferative responses of cord blood lymphocytes (CBLs) to food antigens and cord blood IgE concentrations were measured in 37 full term newborn infants for the prediction of allergic disorders. In these 37 infants who were followed up for two years, allergic history of the family was found in four (sensitivity 57.1%) and cord blood IgE concentrations were greater than 0.5 IU/ml in three (sensitivity 42.9%) of seven infants who developed allergic disorders. When CBLs were stimulated twice by ovalbumin or bovine serum albumin, the value of the stimulation index in proliferative responses of CBLs to ovalbumin or bovine serum albumin was greater than 1.5 in six (sensitivity 85.7%) of seven infants who developed allergic disorders. The specificity of the responses of CBLs in the prediction of the development of allergic disorders was 93.3%. The proliferative responses of CBLs to food antigens were useful in the prediction of not only development of allergic disorders but also offending allergens. These observations provide further evidence that sensitisation is occurring in utero. This would appear to be increasingly important in the genesis of early atopic problems. As our follow up is only two years, in utero sensitisation is a prediction for the early development of atopic disease but only longer follow up will show whether this holds good for allergic disorders at any age. PMID- 1520002 TI - Risk of developing atopic disease after early feeding with cows' milk based formula. AB - A follow up of a cohort of 736 healthy full term children with exposure to cows' milk based formula and breast milk from donors on the maternity ward was performed. The children were divided into three exposure groups according to the feeding patterns on the maternity ward. Group 1 received only mother's milk, group 2 mother's milk and human donors' milk, and group 3 received mother's milk, donors' milk and cows' milk based formula. The children were investigated at 7 years of age, by examining their medical files, and at 11 and 14 years, by questionnaires regarding symptoms of atopic disease. No significant differences between the three groups at follow up were found in the cumulative incidences of atopic diseases. The amount of formula given did not affect the risk of developing atopic disease. Children with a family history of such diseases ran the same risk of subsequent atopic disease whether they were fed formula or breast milk alone. Cows' milk based formula given on the maternity ward does not seem to increase the risk of developing atopic disease. PMID- 1520003 TI - Newly diagnosed diabetes: a study of parental satisfaction. AB - A national survey of 509 parents of children with newly diagnosed diabetes elicited a 92% response rate, showing that 96% of children were admitted to hospital, 42% staying in hospital longer than one week and 41% received an intravenous infusion. More than 90% of parents expressed satisfaction with the information given at diagnosis, the preparation they received before discharge home, and the outpatient follow up services. Home visits from a diabetes nurse specialist (DNS) were received by 73% of families and 44% reported that the DNS was the most supportive person in the first year after diagnosis. Readmission during the first 12 months after diagnosis was required by 23% of children, more often in the youngest age group. Poor liaison with schools and the lack of diabetes knowledge in teachers were the sources of greatest dissatisfaction. Children under the care of paediatricians with no specialist interest in diabetes were significantly more likely to be kept in hospital longer at diagnosis and parents were less satisfied with outpatient care and school liaison. The study supports previous recommendations that diabetes nurse specialists are a priority resource in providing support services and that every district should have a paediatrician with a special interest in diabetes and a designated children's diabetic clinic. PMID- 1520005 TI - Early immune responses to Dermatophagoides pteronyssinus and atopic predisposition. AB - Responses to the house dust mite during infancy may be important determinants of asthma in susceptible individuals. This study assessed early IgG subclass antibody responses to Dermatophagoides pteronyssinus in children of atopic parents. Sixteen atopic and 15 non-atopic children were selected from a birth cohort, and atopic status was established according to follow up over the first two years. IgG1 and IgG4 antibodies to D pteronyssinus were measured by enzyme linked immunosorbent assay at 7 days and 3, 6, 12, and 24 months. In all children D pteronyssinus IgG1 fell at 3 months (indicating maternal antibody loss), rose progressively to 12 months, and waned at 24 months. D pteronyssinus IgG4 was only detectable at 7 days. Children who were atopic by 2 years and therefore at greater risk of asthma, tended to have higher D pteronyssinus IgG1 at 6 and 12 months. These data suggest greater exposure or responsiveness to dust mite during infancy than in the second year. PMID- 1520006 TI - Breast feeding and oral rehydration at home during diarrhoea to prevent dehydration. AB - In a case-control study we evaluated the role of maternal behaviour, as reflected in maintenance of breast feeding and the use of oral rehydration therapy (ORT) at home during acute diarrhoea, in preventing dehydration in infants and young children. A systematic 5% sample was taken of all children aged 1-35 months attending the treatment centre of the International Centre for Diarrhoeal Disease Research, Bangladesh, with acute watery diarrhoea of six days or less between August 1988 and September 1989. There were 285 children with moderate or severe dehydration as cases and 728 with no dehydration as controls in the study. In a multivariate analysis using a logistic regression model we showed that withdrawal of breast feeding during diarrhoea was associated with a five times higher risk of dehydration compared with continuation of breast feeding during diarrhoea at home. Lack of ORT with either complete formula or a salt and sugar solution at home was associated with 57% higher risk of dehydration compared with receipt of a reasonable amount of ORT after controlling for several confounders. The confounding variables--that is, lack of maternal education, history of vomiting, high stool frequency, young age and infection with Vibrio cholerae 01--were also shown to be risk factors of dehydration. Health education programmes should promote continued breast feeding and adequate oral rehydration therapy for infants with acute diarrhoea at home. PMID- 1520004 TI - Genetic risk for asthma, allergic rhinitis, and atopic dermatitis. AB - In order to explore the genetic risk of a child with a family history of allergies developing asthma, allergic rhinitis, or atopic dermatitis, questionnaires filled in by 6665 families were analysed. The data were collected in a population based cross sectional survey of 9-11 year old schoolchildren living in Munich and southern Bavaria. The relation between asthma, allergic rhinitis, and atopic dermatitis and the number of allergic first degree relatives, and the type of allergic disease was examined. Analyses were done separately for families with single or multiple allergic diseases. In families with one allergic parent the risk of the child developing asthma was increased by asthma in a parent, with an odds ratio (OR) of 2.6 (95% confidence interval 1.7 to 4.0) but not by parental allergic rhinitis with OR 1.0 (0.7 to 1.5) or atopic dermatitis, OR 1.0 (0.6 to 1.6). For allergic rhinitis the highest risk with OR 3.6 (2.9 to 4.6) was observed with allergic rhinitis of one parent, apparently lower for asthma of one parent, OR 2.5 (1.6 to 4.0) or atopic dermatitis, OR 1.7 (1.1 to 2.5). Children with parental atopic dermatitis had a high risk for atopic dermatitis, OR 3.4 (2.6 to 4.4), compared with children with parental asthma, OR 1.5 (1.0 to 2.2), or parental allergic rhinitis, OR 1.4 (1.1 to 1.8). Risk factors in families with combined allergies of two relatives (parents and siblings) were analysed separately for the different combinations. These results support the hypothesis that asthma, allergic rhinitis, and atopic dermatitis are multifactorial diseases brought about by various familial and environmental influences. PMID- 1520007 TI - Reversible cerebral shrinkage in kwashiorkor: an MRI study. AB - Protein energy malnutrition is associated with cerebral atrophy which may be detrimental to intellectual development. The aim of this study was to document the anatomical abnormalities which lead to the appearance of cerebral atrophy using magnetic resonance imaging (MRI) in the acute stage of kwashiorkor and to monitor changes during nutritional rehabilitation. Twelve children aged 6 to 37 months requiring admission to hospital for the treatment of kwashiorkor were studied. The children were evaluated clinically, biochemically, and by MRI of their brains on admission and 30 and 90 days later. Brain shrinkage was present in every child on admission. White and grey matter appeared equally affected and the myelination was normal for age. At 90 days, the cerebral changes had resolved in nine and improved substantially in the remainder, by which time serum proteins and weight for age were within the normal range. The findings of this study suggest that brain shrinkage associated with kwashiorkor reverses rapidly with nutritional rehabilitation. PMID- 1520008 TI - Solitary mastocytoma causing recurrent blistering in infancy. AB - Two children with solitary mastocytoma in infancy, both of whom had recurrently blistering scalp lesions, are reported in order to emphasise the diagnostic importance of this distinctive history. PMID- 1520009 TI - Pituitary gigantism. AB - A case of pituitary gigantism resulting from a pituitary adenoma which secreted growth hormone is described. The patient was successfully treated by surgery, which led to the normalisation of endogenous growth hormone secretion. An acceptable final height was achieved with high dose intramuscular testosterone treatment. PMID- 1520010 TI - Paediatric care in Hungary. AB - In this overview, I have attempted to highlight the problems of medical care, particularly paediatric care, in Hungary and to describe the changing nature of its organisation and financing. We hope that through our efforts we can surmount these difficulties, improve the quality of medical care in our country, and create a more rational economic and scientific basis for future medical development and advances. PMID- 1520011 TI - Paediatric liaison. PMID- 1520012 TI - Cerebral palsy--an increasing contributor to severe mental retardation? AB - It is estimated that the prevalence of nongenetic SMR associated with cerebral palsy has risen from 0.7 to about 0.9 per 1000 live births in the last decade. This is due to the predicted rise in total cerebral palsy prevalence to 2.5/1000 live births. This predicted prevalence of cerebral palsy is similar to that given for Western Australia in 1979-82, allowing for postnatal causes, but is higher than prevalence data from England and Sweden for that period. The estimated rise is due largely to improved survival and increased proportion of low birthweight babies since 1983 and also reflects the use of prevalence rates based on Mersey data. Improvements in prenatal diagnosis, and a parental choice of selective termination may lead to reductions in other causes of SMR, such as Down's syndrome and neural tube defects, so it seems that children both physically and mentally handicapped due to brain damage will contribute a greater proportion of the SMR population. The careload of these children is greater than that associated with many other causes of SMR and most survive into adult life. The implications for planning future services will need to be recognised. PMID- 1520013 TI - Guidelines for management of idiopathic thrombocytopenic purpura. The British Paediatric Haematology Group. PMID- 1520014 TI - Asthma: a follow up statement from an international paediatric asthma consensus group. PMID- 1520015 TI - Axillary and rectal temperature measurements in infants. PMID- 1520016 TI - Current status of definitive surgery for congenital heart disease. PMID- 1520017 TI - Haemorrhagic shock encephalopathy syndrome in the British Isles. AB - The aetiopathogenesis of haemorrhagic shock encephalopathy syndrome (HSES) remains unclear and after concern that a novel environmental agent was the cause, the British Paediatric Association and the Public Health Laboratory Service Communicable Disease Surveillance Centre in 1983 initiated surveillance of this condition in the British Isles. After 1986 cases were ascertained via the British Paediatric Surveillance Unit 'active' reporting scheme; this report presents the findings for 1985-8. Sixty five patients were reported, of whom 52 satisfied the criteria for inclusion. Of those whose outcome was known, 24 (46%) died, 18 had severe neurological damage, and six survived apparently intact. Epidemiological features of note were: the median age of 15 weeks (range 3-140); statistically significant clustering of admission times suggesting a peak onset period at night; lack of geographic clusters, of secular trends and, except for a slight excess in winter months, of seasonality. Clinical and pathological features followed a highly consistent pattern, suggesting that HSES is an individual clinical entity distinguishable from conditions with similar presentations, such as septicaemia and Reye's syndrome. There was no microbiological or epidemiological evidence to support the emergence of a novel environmental agent. Many of the features of HSES were, however, the same as those described in heat stroke and we suggest that the two conditions are the same even though there is usually no history of overt overheating. PMID- 1520018 TI - Optimum method for administration of biosynthetic human growth hormone: a randomised crossover trial of an Auto Injector and a pen injection system. AB - The use of optimum conventional growth hormone administration, using a growth hormone vial combined with an Auto Injector, was compared with a pen injection system using a cartridge of growth hormone. In both methods of administration the concentration of growth hormone was 16 IU/ml. Thirty patients (22 boys, eight girls) who had all previously been treated with growth hormone (4 IU/ml) administered using needles and syringes (without an Auto Injector) were randomised into receiving one of either treatment for three months and then crossed over for a further three months. Fourteen patients (10 boys, four girls) initially received KabiVial 16 IU/ml combined with an Auto Injector while 16 patients (12 boys, four girls) were treated with KabiPen 16 IU/ml. Mean age in both groups was 9.6 years. The majority of patients in both groups were treated with a regimen of either 15 or 20 units/m2/week as a daily subcutaneous injection. Of the 30 patients who started in this trial, two who commenced using an Auto Injector refused to change to a pen system and were excluded from further analysis. When scored on a scale of -5 to +5 general convenience when changing from an Auto Injector to the KabiPen decreased from +4.7 to +1.0. When assessed for pain, the Auto Injector group scored +4.7, which decreased to -0.2 (more painful) for the pen. At the end of the trial 23 patients (82%) chose to continue with the KabiVial/Auto Injector combination as they found this less painful and the child did not see the needle or need to insert the needle manually. Five patients (18%) continued with the KabiPen as they considered the device smaller and easier to use. The accuracy of dosing using KabiVial was 100% compared with the range of 88% to 111% using KabiPen as the latter was available only in 0.5 unit increments. No growth hormone was wasted using KabiVial, although a mean of 0.6 units was wasted with every 16 IU cartridge in the KabiPen system. It is concluded that patients should be able to contribute to the choice of growth hormone delivery systems and that newer methods need careful assessment. PMID- 1520020 TI - Quality issues in nurturing research. PMID- 1520021 TI - Delegation of nursing tasks to licensed and unlicensed personnel: a guide for ESRD facilities. PMID- 1520019 TI - Plasma and cerebrospinal fluid arginine vasopressin in patients with and without fever. AB - Hyponatraemia has been described in association with a number of acute infectious diseases, mainly bacterial and tuberculous meningitis and pneumonia, and has been attributed to inappropriate secretion of arginine vasopressin (AVP). The mechanism of inappropriate AVP production is uncertain, but there is experimental evidence to suggest that fever may stimulate secretion of AVP into plasma and cerebrospinal fluid. In this study, AVP concentrations in plasma and cerebrospinal fluid from 37 febrile children with infections have been compared with those from 27 afebrile control subjects. Ten of the febrile children had meningitis (eight bacterial, two viral) and the remainder a variety of other infectious diseases. Seventy four per cent of febrile infected children were hyponatraemic (serum sodium less than 135 mmol/l) compared with only 8% of the afebrile controls. Plasma AVP concentrations were significantly higher in the febrile patients (median 2.92 pmol/l, range 1.0-23.25, n = 28) than in controls (median 1.67 pmol/l, range 0.57-6.0, n = 14) but there was no significant difference in cerebrospinal fluid AVP concentrations. There was no difference in plasma AVP concentrations between patients with meningitis and those with infections not involving the central nervous system. Careful attention should be paid to fluid and electrolyte balance in all children with acute infections. PMID- 1520022 TI - The great Chicago flood of 1992. AB - Despite many years of experience in a chosen field, a systematic response to a disaster situation can only be measured when experiencing such a situation. During the Great Chicago Flood of 1992, our dialysis unit appropriately responded to the various needs of our dialysis population. How each department responded, what steps were taken, and the immediate outcomes in the first critical hour of the disaster are the focus of this article. PMID- 1520023 TI - Testimony: controversies in organ donation. AB - The National Kidney Foundation recently held four regional forums to discuss controversies in organ donation. All interested parties, both in the public and private sectors, were invited to submit written and oral testimony. The following is the written testimony submitted by ANNA and presented orally by Ms. McNatt at the regional forum in Chicago, April 9, 1992. PMID- 1520024 TI - Family styles of coping in end stage renal disease. AB - The introduction of a serious life-threatening illness such as end stage renal disease (ESRD) is an added stress dimension to the already enormous demands placed on the contemporary family system. The purpose of the present study was to identify qualitatively and describe selected aspects of psychosocial adaptation among the families of ESRD patients experiencing four primary modes of dialytic therapy: incenter hemodialysis, home dialysis, continuous ambulatory peritoneal dialysis (CAPD), and continuous cyclic peritoneal dialysis (CCPD). Five family coping styles emerged from content analysis of the data collected from 50 family members at four time periods. These styles have been labelled: Remote Family Style, Enfolded Family Style, Altered Family Style, Distressed Family Style, and Receptive Family Style. PMID- 1520025 TI - Renal physiology series: Part 3 of 8. Urinary concentration and dilution. AB - The maintenance of extracellular volume depends on the appropriate excretion of both salt and water. When extracellular volume is expanded, the excretion of a dilute urine facilitates the return of extracellular volume to normal. When extracellular volume is contracted, the retention of both salt and water and the excretion of a small amount of concentrated urine contributes to the reexpansion of extracellular volume. The formation of either a dilute or concentrated urine is dependent on the physical arrangement of the loops of Henle, collecting tubules, and vasa recta within the kidney medulla, the transport properties of each segment; and the appropriate presence or absence of antidiuretic hormone (ADH), a hormone synthesized in the hypothalamus and secreted from the posterior pituitary gland. PMID- 1520026 TI - Images of nephrology nursing practice: report of a survey. AB - The results of a survey designed to identify existing images of nephrology nursing practice are reported. The sample included 374 attendees at meetings sponsored by the American Nephrology Nurses' Association (ANNA). Content analysis revealed that the typical nephrology patient is elderly, has a chronic illness and negative affect, is not compliant, and is dependent on others. The typical nephrology nurse-patient interaction emphasizes teaching and support. The most common nursing activities are assessment, teaching, dialysis treatment, and psychological support. PMID- 1520027 TI - Varying heparin requirements in hemodialysis patients receiving erythropoietin. AB - A two-phase study was undertaken to investigate the incidence, extent, and management of increased heparin needs occurring during erythropoietin (EPO) therapy in the hemodialysis patient. Individual heparin doses and activated clotting time (ACT) test values were the parameters used to indicate changes in heparin requirements. It appears that increased heparin requirements are frequently associated with EPO therapy, and awareness of this finding, coupled with close ACT monitoring, may possibly prevent complications associated with undetected increases in heparin requirement. PMID- 1520029 TI - 1992 Educational Resource Directory. PMID- 1520028 TI - Successful use of Orthoclone OKT 3 for steroid-resistant acute rejection in pediatric renal allograft recipients. AB - Use of Orthoclone OKT 3 for the treatment of steroid-resistant acute rejection in kidney transplant recipients is well described in the literature. Our experience with the use of OKT 3 in 16 pediatric kidney transplant recipients supports the use of this therapy in the pediatric population by reporting efficacy and lack of major complications. Monitoring of OKT 3 antibodies is recommended because of potential need to reuse OKT 3 in subsequent transplants. In addition, techniques of improving medical compliance, particularly in the adolescent population, is an area identified as needing further study. The combination of improving rejection therapies and specific nursing interventions in preparing children and their families in the use of OKT 3 as well as in enhancing compliance will improve the outlook of pediatric transplant recipients. PMID- 1520030 TI - Administering a heparin loading dose. PMID- 1520031 TI - Acute renal failure secondary to nontraumatic rhabdomyolysis. PMID- 1520033 TI - Promoting cultural sensitivity in the workplace. PMID- 1520032 TI - Case management of the anemic patient. Epoetin alfa: focus on quality of life. AB - Dialysis patients often experience a diminished quality of life. Epoetin alfa therapy, which increases hematocrit, can result in improvements in exercise capacity, cognitive function, and other factors. Nurses play a critical role in monitoring and educating dialysis patients and in helping them achieve an optimal quality of life. PMID- 1520034 TI - Effects of electropermeabilization on the association of foreign DNA with pig sperm. AB - This study was conducted to evaluate the effects of an electric pulse (electroporation/electropermeabilization) on the binding of foreign DNA molecules to porcine spermatozoa. We previously examined various parameters involved in the association of foreign DNA with sperm after a simple incubation procedure and now report the effects of electroporation on this association. Using end-labeled and random primer labeled lambda HindIII DNA fragments (23-0.125 kb), it was demonstrated that the DNA fragments interacted with the sperm after electroporation. These samples were then centrifuged and washed extensively to establish if any of the labeled DNA was associated with the spermatozoa. It was determined that approximately 10(8) molecules of DNA were associated with 1.5 x 10(7) mL-1 motile spermatozoa after five medium washes. After each wash, samples were withdrawn for gel analysis and scintillation counting. Gel analysis followed by autoradiography revealed the distinctive band pattern of lambda HindIII DNA associating with sperm. In situ visualization studies with biotin-labeled DNA revealed that approximately 75% of motile sperm carried DNA bound to the post acrosomal region. However, the intensity of the binding varied, with some sperm being more strongly stained than others. Using [3H]dCTP-labeled DNA followed by light microscope autoradiography, approximately 70% of the sperm were strongly stained in the post-acrosomal region. There was a 5-10% increase in the amount of DNA bound by sperm when the samples were electroporated. PMID- 1520035 TI - Influence of male sexual rest and oocyte aging on parthenogenesis frequency in mice: cytogenetic analysis after in vitro fertilization. AB - This study was conducted to evaluate the influence of male sexual rest and oocyte aging on fertilization rate and parthenogenesis frequency after in vitro fertilization of mouse oocytes. We used a comparison between cleavage rates and fertilization rates according to chromosomal analysis of oocytes to estimate the parthenogenesis frequency. Fertilization rate was not impaired by male sexual rest. Parthenogenesis frequency was increased by male sexual rest. This effect was enhanced by a concomitant moderate oocyte aging. It is concluded that cleavage rate could not be considered as a reliable test of fertilization after attempted in vitro fertilization in such conditions. PMID- 1520036 TI - Sex ratio of male sex preselected children born to couples with exclusively female offspring. AB - The present study was undertaken to determine if couples with exclusively female children had a decreased probability of a male child after using male sex preselection. Selection criteria for subjects necessitated that couples have had only female children previously and had produced a child at one of 14 centers after using protocol 3 (n = 70) and modified 3 (n = 28) male sex preselection. Prior to sex selection, protocol 3 couples produced a combined total of 135 female children for an average of 2.01 (range 1-4) females per couple; modified 3 couples produced a combined total of 62 female children for an average of 2.21 (range 1-4) females per couple. The normal approximation to the binomial distribution was used to determine significant differences between the sex ratios prior to and after male sex preselection. For couples using protocol 3 there were significant differences in the sex ratio prior to sex preselection (0%) and after sex preselection (73.0%) (p less than .00003). There were also significant differences between the sex ratio prior to modified 3 (0%) and after sex preselection (86%) (p less than .00003). Couples using male sex preselection do not have a decreased probability of a male child if they have had exclusively female children. PMID- 1520037 TI - Seminal plasma transferrin in infertile men. AB - Seminal plasma transferrin levels were estimated in 51 men with various infertility problems and in 15 fertile subjects. The estimation of transferrin was carried out by using the radial immunodiffusion technique on LC-partigen transferrin plates. The mean value of transferrin decreased (p less than .05) in cases of azoospermia (91 +/- 51 micrograms/ejaculate). No significant difference was found in other sperm quality disorders (asthenoteratospermia = 227 +/- 141, mild OTA = 186 +/- 96, severe OTA = 247 +/- 137 micrograms/ejaculate). The mean value of transferrin decreased (p less than .05) in obstructive azoospermia cases (73 +/- 70 micrograms/ejaculate), whereas in the other causes of infertility no statistical differences were found. Transferrin was correlated with sperm count, sperm volume, and serum LH. PMID- 1520038 TI - NADH-dependent oxidoreductase (diaphorase) activity and isozyme pattern of sperm in infertile men. AB - Diaphorase activities were measured in spermatozoa from 104 infertile men. The relationships between enzyme activity, sperm characteristics (density, motility, viability), and distribution of electrophoretic patterns were examined. There was a highly significant difference (p less than .001) between the sperm diaphorase activities in specimens with sperm concentration above 40 million per milliliter (0.685 +/- 0.5 mIU/10(6) sperm; n = 57) when compared with the diaphorase values of the oligospermic specimens with sperm density below 40 million per milliliter (1.53 +/- 1.5 mIU/10(6) sperm; n = 47). However, there was no evidence to support any relationship between sperm diaphorase activities, sperm motility, viability, and the distribution of three diaphorase electrophoretic patterns. This indicates that these parameters do not account for the differences between the diaphorase activity of spermatozoa of infertile men with sperm concentrations below and those above 40 million per milliliter. PMID- 1520039 TI - Sperm motility should be assessed in fresh sperm and after a sperm washing procedure. AB - A prospective study was carried out on semen samples from 118 consecutive unselected men attending our infertility clinic to determine whether sperm motility may be affected by seminal plasma. The incidence of asthenozoospermia as defined by fewer than 50% of spermatozoa with forward progressive motility in the untreated semen was 37.4%. This value was significantly reduced to 23% after washing and removing seminal plasma. Men with asthenozoospermia in untreated semen but normal in the washed sample had a percentage of normal sperm morphology and a percentage of swollen tails in the HOS test similar to those of controls, and higher than those of asthenozoospermics in both the untreated and washed sample. Sperm velocity was also significantly improved after the washing procedure. Spermatozoa selected by swim-down procedure and applied to a seminal plasma medium reduced sperm motility affecting negatively the HOS test. Sperm motility should be assessed after a sperm washing procedure, since seminal plasma contains constituents that decrease sperm motility without affecting membrane integrity. PMID- 1520040 TI - Expression of a gene encoding a specific human sperm protein in Chinese hamster ovarian cells. AB - The cDNA (RSD-2) encoding a human sperm protein (YWK-II) was isolated from a rat testis lambda gt11 expression library. Its nucleotide sequence was determined. The deduced polypeptide showed high identity with the transmembrane-cytoplasmic domains of A4 amyloid precursor protein of Alzheimer's disease. The RSD-2 was inserted into the EcoRI site of the pSV2-EP vector to construct the pSVRS-2 vector. Chinese hamster ovarian (CHO-dhfr) cells were cotransformed with pSV2-neo and pSVRS-2. mRNA and chromosomal DNA prepared from the transformed cells interacted with [32P]RSD-2 as probe by dot hybridization. The production of the YWK-II protein was determined by staining with the YWK-II mAb by an indirect immunofluorescence technique. There was marked staining of the cytoplasm. The RSD 2 cDNA encoding the YWK-II sperm was expressed in the transformed CHO cells. The pSV2-EP vector and the CHO cell expression system can be utilized to produce sperm proteins for antifertility studies. PMID- 1520041 TI - Use of theophylline to enhance sperm function. AB - Poor sperm motility is an important factor in male infertility. Preliminary results in our laboratory on a group of 19 men (10 suspected infertile men and 9 fertile donors) showed stimulation of sperm fertilizing ability after sperm washing with theophylline as demonstrated by zona free hamster egg penetration test. The egg penetration rate for the control spermatozoa samples from subfertile men was 16%. Incubation with theophylline (10 mM) increased the penetration rate to 46%, whereas semen incubation with theophylline (20 mM) increased the penetration rate to 51%. A similar twofold increase in egg penetration was observed in the semen of fertile men incubated with theophylline of similar concentrations. Subfertile patients with ejaculate volumes of less than or equal to 1 ml or total motile sperm count of less than or equal to 10 x 10(6)/mL or increased semen viscosity did not exhibit beneficial effects with theophylline washing as measured by hamster egg penetration test score. The increase in percentage of penetrated eggs with theophylline use in both fertile and subfertile men was significant at 10 mM concentration (p less than .001) and 20 mM (p less than .001) when compared to control (untreated) samples. No significant difference in penetration rate was seen between 10 and 20 mM theophylline concentrations. It appears that theophylline may be useful in improving the fertilizing capacity of selected human semen samples with poor motility and poor penetration ability under artificial insemination conditions. PMID- 1520042 TI - What is eosinophilic pneumonia? PMID- 1520043 TI - Pharmacy and Therapeutics committee. Cost-containment considerations. AB - The Pharmacy and Therapeutics committee is a frequently used mechanism for health care organizations to meet mandated standards. The control that the committee has over the formulary is often seen as a potential way of controlling the expenditures for drugs. As the Pharmacy and Therapeutics committee is the means for the clinical staff to have an effect as to what agents are available to practitioners, it is incumbent on the committee members to have a clear idea of what their role should be in cost containment. An important concept that impacts on cost is that optimal health benefit is not necessarily the result of maximum expenditure. The welfare of the patient is paramount to all in the health care field; however, it is the task of clinicians to determine what constitutes optimal health benefit and to act as agents of the patient. Clinicians must maintain patient care as their top priority. Although health care expenditures are an extremely important issue, quality of patient care cannot be subrogated to a secondary concern. PMID- 1520044 TI - Significance of distal polyps detected with flexible sigmoidoscopy in asymptomatic patients. AB - BACKGROUND: Colorectal cancer is a frequent cause of death from cancer. To reduce the mortality associated with this disease, regular flexible sigmoidoscopy is recommended. However, the significance of diminutive polyps (adenomatous or hyperplastic) detected during flexible sigmoidoscopy remains controversial, as does the appropriate endoscope length (35 vs 60 cm) for colorectal cancer screening. METHODS: One hundred one consecutive patients with no history of colonic disease, gastrointestinal tract symptoms, or positive results of fecal occult blood testing underwent flexible sigmoidoscopy as part of a colorectal cancer screening program. All patients with distal polyps detected during flexible sigmoidoscopy underwent colonoscopy. RESULTS: More than 25% of these asymptomatic, predominantly male subjects had colonic neoplasms or polyps detected. Fifty percent more lesions could be detected with a 60-cm sigmoidoscope than with a 35-cm sigmoidoscope, and detection of any distal polyp, whether adenomatous or hyperplastic, was associated with at least one proximal colon adenoma in 20% of patients. "Extended flexible sigmoidoscopy" for colorectal cancer screening was well tolerated by patients, as evidenced by insertion to the hepatic flexure in 25% of patients, and provided significantly more information than could be obtained with a 35-cm sigmoidoscope. CONCLUSIONS: Colorectal cancer screening should be performed with a 60-cm flexible sigmoidoscope, and distal colonic polyps or neoplasms will be detected in 25% of asymptomatic patients. PMID- 1520045 TI - Comparison of gemfibrozil and lovastatin in patients with high low-density lipoprotein and low high-density lipoprotein cholesterol levels. AB - BACKGROUND: The efficacy of gemfibrozil and lovastatin in the treatment of patients who have an elevated low-density lipoprotein cholesterol (LDL-C) level and a low high-density lipoprotein cholesterol (HDL-C) level was compared. METHODS: After at least 6 weeks of a cholestgerol-lowering diet, 17 patients who had a mean baseline LDL-C level above 4.14 mmol/L (160 mg/dL) and an HDL-C level below 1.03 mmol/L (40 mg/dL) received gemfibrozil 600 mg twice daily and lovastatin 20 mg twice daily each for 6 weeks according to a randomized, crossover, double-blind research design. RESULTS: Lovastatin and gemfibrozil reduced LDL-C levels 34% and 9% and raised HDL-C levels 15% and 18%, respectively. CONCLUSIONS: Lovastatin is more effective in lowering LDL-C levels and is as effective as gemfibrozil in increasing HDL-C levels in these patients. PMID- 1520046 TI - Impact of human immunodeficiency virus on medical and surgical residents. AB - BACKGROUND--Previous surveys of resident physicians on human immunodeficiency virus (HIV) matters have tended to focus on urban programs serving a patient population with an expected high prevalence of HIV infection. The objective of this study was to survey a community hospital residency program in a nonurban area with a perceived low HIV patient seroprevalence. METHODS--A 32-question survey was completed on an anonymous basis by the entire 74 member multidisciplinary resident physician group at a two-campus university-affiliated hospital program in southeastern Pennsylvania in May 1991. RESULTS--Residents perceived their patient population's HIV seroprevalence rate to be low although they believed their personal risk of occupational exposure to blood-borne infection was moderate to high. House staff most often complied with universal precautions for fear of acquiring a blood-borne illness and most often did not comply because of time constraints. Not perceiving the exposure as a health risk was the primary reason for nonreporting of exposures. Occupational exposure rates were alarmingly high, with suturing using a curved needle being the most common exposure method. Most residents were unfamiliar with HIV legislation. A majority of the house staff wanted improved HIV patient management training and life and disability insurance against occupationally acquired HIV. Many other important issues were addressed in this survey. CONCLUSION--Residents even in low seroprevalence environments do fear occupationally acquired HIV. A great need exists for improved training in universal precautions, acquired immunodeficiency syndrome legislation, and HIV patient management as well as for insurance against occupationally acquired HIV. PMID- 1520047 TI - Pneumococcal pneumonia in adult hospitalized patients infected with the human immunodeficiency virus. AB - PURPOSE: To determine the attack rate; clinical, radiologic, and laboratory characteristics; and outcome of pneumococcal pneumonia in patients infected with the human immunodeficiency virus (HIV) and to compare these characteristics with those of pneumococcal pneumonia in the general population. PATIENTS AND METHODS: This is a retrospective (13-month), prospective (14-month) study. All adult hospitalized patients with pulmonary infiltrates and isolation of Streptococcus pneumoniae in blood, pleural fluid, transtracheal aspirate, or respiratory secretions obtained by plugged telescoped catheter (counts greater than 10(3) colony-forming units per milliliter) are included. MAIN RESULTS: We identified 22 HIV-infected patients and 84 HIV-seronegative patients with pneumococcal pneumonia (76% and 56%, respectively, were bacteremic). The estimated attack rate was 5.9 per 1000 for HIV-infected patients and 0.31 per 1000 for HIV-seronegative patients. Pneumococcal pneumonia was the first manifestation of HIV infection in 48% of cases. Seventy-two percent of patients younger than 40 years of age with pneumococcal pneumonia were HIV infected. No predisposing factors for pneumococcal pneumonia were identified in 76% and 2% of HIV seropositive and seronegative patients, respectively. Clinical and radiologic presentation was similar in the two populations. Of all S pneumoniae isolates, 35% were resistant to penicillin and 10% to erythromycin, without differences in the two groups. Prognosis was good, with only one infection-related death in the HIV-infected group (10 patients died in the other group). No relapses were documented in HIV infected patients. CONCLUSION: The HIV-infected patient is at increased risk for pneumococcal pneumonia and bacteremia. Patients younger than 40 years of age who present with pneumococcal pneumonia should be considered for HIV testing, since it may be the first manifestation of HIV infection. Specific antimicrobial therapy is curative in the majority of HIV-infected patients. PMID- 1520048 TI - Teaching medical interviewing. A basic course on interviewing and the physician patient relationship. AB - Recent advances in educational theory and methodology have made it possible to teach medical interviewing with as much rigor as other clinical skills. We describe a first-semester, first-year medical student course that effectively teaches basic interviewing skills. This course provides faculty development, small group learning, detailed faculty and student coursebooks, and an interview checklist that delineates specific interviewing skills and content areas, serving as a template for teaching, practice, and feedback. Students have many opportunities for practice in role play and with patients, followed by feedback by self, peers, and faculty. Use of audiotape and videotape reviews enhances the learning experience. This article describes our course, suggests educational principles and standards for the teaching of medical interviewing, and presents educational research demonstrating significant gains in students' skills associated with improvement in standardized patient satisfaction. PMID- 1520049 TI - The effect of educational preparation on physician performance with a sexually transmitted disease-simulated patient. AB - BACKGROUND: Simulated patients are used with increased frequency for medical students and residents, but have not been used very often with practicing physicians. We hypothesized that educational materials could improve primary care physicians sexual practices history taking and counseling as assessed by a simulated patient in the physician's office. METHODS: Simulated patient (SP) visits were made to 232 (75% of eligible) primary care physicians. The patient simulated was a sexually active young woman with vaginitis and sexually transmitted disease/human immunodeficiency virus risk behaviors. In advance of the visit, physicians were provided educational materials (monograph, pamphlet, and audiotape) developed for the study, including a risk assessment questionnaire that could be used with patients. RESULTS: Most physicians randomly allocated to the intervention participated. Twenty-one percent of physicians refused to schedule an SP visit. Physicians who received an SP rated the experience highly. Physicians who prepared for the visit with the educational materials performed significantly better than those who did not. About two thirds of physicians reviewed the materials, many for the second time, after the SP visit. Physicians who used the study risk assessment questionnaire performed better. Many physicians (24.9% to 39.8%) did not meet each of the four goals for the visit, as assessed subjectively by the SP. Physician performance was better for measures of general patient interaction than for measures of sexual practices history taking and counseling techniques. CONCLUSION: The SP visit was acceptable to most physicians practicing in a community and was evaluated by them as an appealing and an effective educational experience. The SP, however, has limited feasibility because of cost. The SP led to review of materials by nearly all physicians either before or after the visit. Physicians who prepared before the visit performed better on every dimension, eliciting more information, displaying better patient interaction skills, and meeting more of the educational goals. Even with educational preparation, however, many physicians were not perceived as being effective counselors. PMID- 1520050 TI - Effectiveness and efficiency of selective vs universal screening for chlamydial infection in sexually active young women. AB - BACKGROUND: Since chlamydial cervicitis is not associated with specific complaints, screening asymptomatic women is an important initiative to prevent pelvic inflammatory disease and its sequelae. Compared with universal screening, selective screening is less costly but less effective so the cost savings vs the consequences of missing infected women need to be weighed carefully. METHODS: In two family planning clinics, 1002 women were surveyed for chlamydial infection (prevalence, 7%) and its predictors to determine whether universal or selective screening is the most efficient strategy. Two rules for the selection of patients were determined by logistic regression modeling and their relative efficiencies were compared by incremental cost-effectiveness and sensitivity analysis. The validity of the screening rules was tested in 191 students attending a university health clinic. RESULTS: If those with cervical friability, suspicious discharge, urinary frequency, or intermenstrual bleeding had been tested, 55.3% of all women would have been screened and 83.3% of all cases would have been detected. If those reporting a new sex partner in the preceding year had also been tested, 75.4% would have been screened, identifying 93.3% of all cases. The predictive power and practicality of the selection rules were validated in the university health clinic sample. Sensitivity analyses showed selective screening using cervical enzyme immunoassay with blocking confirmation was efficient if the prevalence of chlamydial infection was 16% or less, 11% or less, or 5% or less depending on whether base analyses, overestimated costs, or worst performance scenarios, respectively, were used. CONCLUSIONS: Selective screening based on four or five predictors and confirmed cervical enzyme immunoassay is an effective and efficient strategy in low prevalence settings. PMID- 1520051 TI - Half a loaf is better than waiting for the bread truck. A computerized mini medical record for outpatient care. AB - We describe a locally developed system for partial computer storage of medical data, called the mini-medical record system. The system produces a typed face sheet prior to each patient visit. The face sheet, which also serves as a progress note, contains patient demographic data, medical problem lists, previous vital signs, allergies, medication profile, and health maintenance reminders. Between regularly scheduled visits, all computerized data are available by computer printout for unscheduled visits to walk-in clinics and the emergency department. Structured reports are generated by the system that describes each resident and faculty members' practice. Quality assurance reports are also available. Since the system draws from several already existing databases, new data entry requirements are modest and cost to the institution is low. Partially computerized systems can be developed inexpensively and are well received in multispecialty practices, where interphysician communication is vital. PMID- 1520052 TI - Epidemiology of bacterial endocarditis in The Netherlands. I. Patient characteristics. AB - BACKGROUND: Studies of the epidemiology of bacterial endocarditis are usually based on a retrospective review of medical records from referral centers serving diverse patient populations. These studies are therefore likely to suffer from selection bias. We conducted a nationwide prospective epidemiologic study of endocarditis in the Netherlands. METHODS: During a 2-year period, all cases of consecutively hospitalized patients with suspected endocarditis in the Netherlands were reported to us. While hospitalized, patients were visited for an in-person interview and a review of the medical record. RESULTS: Of 559 episodes, 438 met the criteria for endocarditis; these included 89 episodes of prosthetic valve endocarditis and 349 episodes of native valve endocarditis. Adjusted for age- and sex-specific population figures, the incidence was 19 per million person years. The incidence increased significantly with age, and men were more often affected than women (266 and 172 cases, respectively). Rheumatic and congenital cardiac lesions formed most of the underlying heart diseases. Mitral valve prolapse was present in only 29 patients with native valve endocarditis (8.3%). A history of intravenous drug abuse was present in 32 patients (7.3%). Viridans streptococci, staphylococci, and enterococci together constituted 86% of the isolated bacterial strains. Only 1.1% of the patients had culture-negative endocarditis. Overall case fatality was 19.7% and varied widely according to causative microorganism. CONCLUSION: The distribution of causal microorganisms, the case fatality rate, and the incidence rate of endocarditis are age related. Therefore, a meaningful comparison of data is only possible between population based cohorts of patients with endocarditis. PMID- 1520053 TI - Epidemiology of bacterial endocarditis in The Netherlands. II. Antecedent procedures and use of prophylaxis. AB - BACKGROUND: The reported frequency with which endocarditis is ascribed to an antecedent dental or medical procedure varies from 3% to 62%. METHODS: We performed a nationwide prospective study of the epidemiology of bacterial endocarditis in the Netherlands. During a 2-year period, all consecutively hospitalized patients suspected of having endocarditis were visited while still hospitalized for a review of the medical record and an in-person interview that focused on antecedent procedures and administered prophylaxis. All information was checked with pharmacists and dental and medical practitioners. RESULTS: Of 427 patients with late prosthetic or native valve endocarditis, 275 were eligible for antibiotic prophylaxis because of a previously known cardiac lesion (n = 197) or a prosthetic valve (n = 78). Of these 275 patients, 64 (23.3%) had undergone a procedure with an indication for prophylaxis within 180 days of onset; in 31 (11.3%) the procedures had been within 30 days of onset. Antibiotic prophylaxis had been administered to 17 (26.6%) of the 64 patients and to eight (25.8%) of the 31 patients. CONCLUSION: The results indicate that medical and dental procedures cause only a small fraction of endocarditis. The majority of patients develop the disease along other routes. For an incubation period of 180 days, full compliance with prophylaxis might have prevented endocarditis in 47 (17.1%) of 275 patients with late prosthetic or native valve endocarditis involving a previously known cardiac lesion who underwent a procedure with an indication for prophylaxis. For an incubation period of 30 days, prophylaxis might have prevented endocarditis in 23 (8.4%) of these 275 patients, or 5.3% of all patients with endocarditis (n = 427). PMID- 1520054 TI - Treatment of nocturnal leg cramps. A crossover trial of quinine vs vitamin E. AB - OBJECTIVE: This study compared the efficacy and safety of quinine sulfate, vitamin E, and placebo in the treatment of nocturnal leg cramps. DESIGN: A random order, double-blind, placebo-controlled crossover trial was performed. SETTING: The study was conducted at the Veterans Affairs Medical Center, White River Junction, Vt. PARTICIPANTS: Twenty-seven male veterans, aged 38 to 73 years, who experienced at least six leg cramps per month were recruited through the general medicine walk-in clinic or were referred from other clinics. Fifty-five subjects were contacted, 30 were enrolled consecutively, and 27 completed the study. INTERVENTION: Subjects received, in random order, quinine sulfate (200 mg at supper and 300 mg at bedtime), vitamin E (800 U at bedtime), or placebo for 4 week periods. These periods were separated by 4-week washout intervals. OUTCOME MEASURES: Patients reported cramp frequency, severity, and sleep disturbance caused by cramps. RESULTS: Compared with treatment with placebo, quinine reduced the frequency of cramps and sleep disturbance, but not the average cramp severity. Thirteen of 27 patients had at least a 50% reduction in the number of cramps while receiving quinine; the response was usually seen within 3 days. There was evidence of a mild increase in side effects while subjects received quinine. Vitamin E was not effective in reducing leg cramp frequency, severity, or sleep disturbance. CONCLUSIONS: Quinine sulfate, but not vitamin E, is superior to placebo in the treatment of nocturnal leg cramps. PMID- 1520055 TI - Community-acquired invasive group A beta-hemolytic streptococcal infections in Zuni Indians. AB - BACKGROUND: Outbreaks of invasive group A beta-hemolytic streptococcal (GABS) infections have recently been reported. We observed a high incidence of invasive GABS disease among Native Americans at a small rural community hospital between 1982 and 1991. METHODS: A retrospective chart review was performed, and all cases of invasive GABS disease were studied for their clinical features. RESULTS: Sixteen cases of invasive GABS infection were identified during the 10-year study period. The rate of invasive GABS infection was 13.3 cases per 100,000 population per year. Mortality was 25%. Nearly half of the patients presented with systemic signs of sepsis without any obvious source of infection. CONCLUSIONS: Our experience documents a high rate of invasive GABS infections in a defined Native American population. To determine whether this population has a unique susceptibility to GABS disease requires further study. PMID- 1520056 TI - Surrogate decision-maker preferences for medical care of severely demented nursing home patients. AB - BACKGROUND: In the absence of advanced directives, physicians treating demented patients rely on surrogates to help make medical care decisions. METHOD: We surveyed family members of severely demented nursing home residents to determine preferences for medical intervention in five hypothetical situations involving tube feeding, hospitalization, intensive care unit admission, mechanical ventilation, and cardiopulmonary resuscitation. RESULTS: Only 11.8% of surrogates rejected all interventions. Cardiopulmonary resuscitation and tube feeding were accepted least frequently (31.6% and 36.4%, respectively). Mechanical ventilation, hospitalization, and intensive care unit admission were accepted by 43.6%, 63.4%, and 75.2%, respectively. There was no correlation between previous surrogate experience with an intervention and its acceptance. Nearly 70% of surrogates indicated that decisions were independent of any previously expressed resident views. CONCLUSIONS: In this study, surrogates of even the most demented nursing home patients prefer hospital level services including intensive care unit care for the treatment of acute illness. Efforts to control access to services on ethical or economic grounds may meet with resistance. PMID- 1520057 TI - Eosinophilia-myalgia syndrome. Natural history in a population-based cohort. AB - BACKGROUND: To determine the natural history of eosinophilia-myalgia syndrome, we followed up all patients with eosinophilia-myalgia syndrome reported to the Oregon Health Division, Portland, during the recent epidemic caused by contaminated tryptophan. METHODS: Patients were interviewed by telephone from 1 to 5 months after illness onset and again at least 12 months after onset. Symptoms (type, onset, and duration), overall disability, treatment, and tryptophan lot and dose were assessed for each patient. RESULTS: Information was obtained for 55 (96%) of 57 case-patients: 53 patients completed interviews and two patients had died. For the 53 patients who were interviewed, symptoms with onset more commonly during the first 3 months of illness included severe myalgias, fatigue, generalized weakness, edema, and rash. Symptoms with later onset included paresthesias, muscle cramps, extremity weakness, and alopecia. At 12 months, 41 patients (77%) continued to report fatigue, 36 (68%) weakness, and 34 (64%) myalgias; 26 patients (49%) had difficulty climbing stairs, 23 (43%) had difficulty getting up from a chair, and 15 (28%) had difficulty holding a cup. Higher doses of tryptophan were correlated with more severe disability, both initially (rs = .33) and at follow-up (rs = .42). Although most patients reported improvement in symptoms at 12 months, only 14 (26%) patients reported that they were able to perform all normal daily activities. CONCLUSIONS: Most patients with eosinophilia-myalgia syndrome in this population-based cohort are still symptomatic 1 year after onset, primarily with the complaints reported early in the illness. The association between degree of disability and daily tryptophan dose suggests that ingestion of varying amounts of contaminant may be responsible, in part, for the severity of symptoms experienced by individual patients. PMID- 1520058 TI - Twelve cases of pituitary apoplexy. AB - In 12 cases of pituitary apoplexy, a preexisting unsuspected adenoma was found. The initial manifestations were sudden onset of headache (12 patients), signs of meningeal irritation (10) with fever (four), altered consciousness (12), and ophthalmologic disturbances (eight). The diagnosis was retrospective in three cases. Radiologic investigations were always suggestive if carefully considered. The plain skull roentgenograms, in particular, showed an enlarged sella turcica in 11 cases. Three patients had prolactin adenomas, and nine had nonfunctional adenomas. Medical treatment was successful in only three patients; surgery was performed in 10 cases by means of a sublabial transseptal microsurgical approach. Postoperative neurologic complications were serious in two cases. Endocrine insufficiencies were common: eight cases of permanent panhypopituitarism, two cases of pluritropic anterior pituitary dysfunction, and three cases of persistent hyperprolactinemia. PMID- 1520059 TI - Detection of deep vein thrombosis with impedance plethysmography and real-time compression ultrasonography in hospitalized patients. AB - BACKGROUND: Serial testing with impedance plethysmography or compression ultrasonography has been demonstrated to be feasible and accurate for the detection of deep vein thrombosis (DVT) in symptomatic outpatients, and these techniques are replacing contrast venography in this patient category. Limited data, however, are available on the clinical utility of these noninvasive tests in symptomatic hospitalized patients. The objectives of our study were to determine the feasibility of ascending contrast venography and to evaluate the accuracy of these two noninvasive methods for the detection of DVT in symptomatic hospitalized patients. METHODS: A prospective, "blind" comparison of impedance plethysmography and compression ultrasonography with ascending contrast venography was performed in consecutive hospitalized patients with clinically suspected DVT of the leg. RESULTS: Of the 127 potentially eligible patients, 44 had to be excluded; 25 of these could not undergo venography (feasibility of venography, 80.3%). The sensitivity, specificity, and positive and negative predictive values of impedance plethysmography for proximal DVT were 96%, 83%, 82%, and 97%, respectively. For compression ultrasonography, these measures for proximal DVT were 97%, 86%, 87%, and 97%, respectively. The overall prevalence of DVT was 53%, of which 85% was located proximally. CONCLUSIONS: Contrast venography cannot be performed in about 20% of consecutive symptomatic patients. Both impedance plethysmography and compression ultrasonography are feasible and valid alternatives to contrast venography in the diagnostic treatment of these patients. PMID- 1520060 TI - Reevaluation of eosinophilic pneumonia and its diagnostic criteria. AB - Eosinophilic pneumonia has been defined as pulmonary infiltration of the lung by eosinophils that may or may not be accompanied by an excess of these cells in the peripheral blood. However, the concept of this disease and its nomenclature have not yet been established. In the present study, the clinical course of 11 cases of eosinophilic pneumonia, which were clinico-pathohistologically diagnosed and found not to be associated with organic disorders producing peripheral blood eosinophilia, were investigated extensively and compared with various types of eosinophilic pneumonia, as previously reported. Of five cases of acute eosinophilic pneumonia with a history (less than 1 month) of symptoms before diagnosis, a short clinical course, and no recurrence, four cases showed peripheral blood eosinophilia, and four cases did not require treatment with steroids. Of six cases of chronic eosinophilic pneumonia with a history (greater than 2 months) of symptoms before diagnosis, a prolonged clinical course, and recurrence, all showed peripheral blood eosinophilia, four cases required treatment with steroids, and four cases were recurrent. In one case with simultaneous occurrence of asthma and another case with asthma that occurred 4 years after the appearance of eosinophilic pneumonia, abnormal shadows on chest roentgenograms had continued for several years. These results suggested that various types of previously reported eosinophilic pneumonia classified by sex, the presence or absence of peripheral blood eosinophilia, the degree of clinical symptoms or peripheral blood eosinophilia, and the degree of abnormalities on the chest roentgenograms should be extensively reevaluated. PMID- 1520061 TI - Papulo-pruritic eruption and giant ulceration of the mouth: a difficult clinical feature to treat in the patient infected with human immunodeficiency virus. PMID- 1520062 TI - Creating immediate medical leadership in geriatrics. PMID- 1520063 TI - Verapamil toxicity and renal failure. PMID- 1520064 TI - Checking for fecal occult blood with digital rectal examinations. PMID- 1520065 TI - Light exposure in a subset of patients with lupus erythematosus. PMID- 1520066 TI - [Studies on the mechanism of late asthmatic response by Candida antigen inhalation using bronchoalveolar lavage]. AB - To elucidate the mechanism of late asthmatic response (LAR), which is related to intractable asthma attack, the cellular and humoral components of LAR were examined in bronchoalveolar lavage fluid (BALF) obtained after bronchial inhalation tests with Candida allergen on Candida-sensitive asthma patients. BAL examination was carried out 2 hours after remission of LAR, and differential cell counts and measurements of leukotrienes (LTs) by high performance liquid chromatography were investigated in BALF and peripheral blood. The number of neutrophils and basophils in circulating blood showed a peak before LAR, and then decreased markedly at LAR. And an increase in the percentage of eosinophils (p less than 0.01) and neutrophils was evident in BALF after LAR compared with the level in the non-attack state. The percentage of basophil-mast cells, however, did not change in the same manner. The serum level of LTC4 increased significantly at LAR in comparison with its level in the phase before LAR. And the level of LTC4 was also significantly higher in BALF after LAR (p less than 0.01). However, LTD4 and LTB4 were at almost undetectable levels in BALF in the non-attack state and after LAR. The results indicate that neutrophils as well as eosinophils may accumulate and release several kinds of leukotrienes at local sites in late asthmatic response provoked by the inhalation of Candida antigen; this gives clues as to the mechanism of severe and intractable asthma attacks. PMID- 1520067 TI - [Studies on the T-cell subset in lung tissue and BALF from patients with interstitial pneumonia]. AB - The cellular components in bronchoalveolar lavage fluids (BALF) have been analyzed to obtain information on cellular kinetics in lung tissues of patients with diffuse pulmonary diseases. While various cells, alveolar macrophages, lymphocytes, and granulocytes appear in BALF, an increase in the percentage of lymphocytes has been noted in a variety of interstitial pneumonia. The T-cell subset of lymphocytes in BALF and biopsied lung tissues was, therefore, examined in patients with hypersensitivity pneumonitis (HP), sarcoidosis (Sar), idiopathic interstitial pneumonia (IIP) and rheumatoid arthritis with interstitial pneumonia (RA+IP) to compare the ratios of CD4/CD8 in BALF and lung tissues. The T-cell subset in BALF was analyzed by flow cytometry and the T-cell subset in lung tissues was detected with fresh frozen and thin-sliced specimens using an avidine biotin complex (ABC) kit (Vecta Co. Ltd). The mean CD4/CD8 ratio in BALF was 0.36 in HP, 3.1 in Sar, 1.07 in IIP and 2.59 in RA+IP, while the mean CD4/CD8 ratio in lung tissues was 0.52 in HP, 2.59 in Sar, 1.11 in IIP and 2.25 in RA+IP, respectively. The ratios of CD4/CD8 in BALF and lung tissues from patients with these various interstitial pneumonia showed a positive correlation indicating that the changes of cellular components in BALF would reflect the changes in the lung tissues. Furthermore, CD4/CD8 ratios of lymphocytes infiltrating the alveolar portion and granuloma in lung tissues of HP were analyzed separately, because the CD4/CD8 ratios varied considerably from part to part of the lung tissues.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1520068 TI - [Role of thromboxane A2 and prostaglandin I2 in the increase of airway responsiveness in dogs after ozone exposure]. AB - To investigate the role of thromboxane (Tx) A2 and prostaglandin (PG) I2 in the development of airway responsiveness after ozone exposure, we measured the airway responsiveness to inhaled methacholine (Mch), TxB2 and 6-keto-PGF1 alpha levels in bronchoalveolar lavage fluid (BALF) in 18 dogs after ozone exposure. Airway responsiveness to Mch was determined by Astograph (7 Hz oscillation method), and ozone exposure was carried out for 2 hr at an ozone level of 3.01 +/- 0.05 ppm (mean +/- SEM). Airway responsiveness to Mch increased significantly after ozone exposure (p less than 0.001). TxB2 levels in BALF were not affected by ozone exposure, but the levels of 6-keto-PGF1 alpha decreased significantly after ozone exposure (p less than 0.001). The ratio of TxB2/6-keto-PGF1 alpha increased significantly after ozone exposure, and the change in this ratio correlated significantly with the change of airway responsiveness to Mch (p less than 0.01, r = 0.654). These results suggest that airway hyperresponsiveness after ozone exposure is induced by the relative increase of TxA2 due to the decrease of PGI2. PMID- 1520069 TI - [Platelet activating factor (PAF)-induced late asthmatic response in sensitized but not in non-sensitized guinea pigs]. AB - We have recently demonstrated that pretreatment with WEB 2086, a specific PAF antagonist or cyclosporine A (CsA), a potent helper T cell suppressant, resulted in preventing the development of late asthmatic response (LAR) and increase of airway hyperreactivity (AH) in guinea pig experimental models of asthma. We have now examined whether exogenously applied PAF causes LAR in these models in vivo. The respiratory resistance (Rrs) of guinea pigs was measured by an oscillation technique and histological studies of the bronchi were also made. Guinea pigs, actively sensitized by repeated antigen (ovalbumin; OA) inhalation, showed a leftward shift of the inhaled PAF dose response curve of Rrs compared with that in control animals, indicating that the sensitized animals were more sensitive to inhaled, PAF. PC200 PAF, which indicate provocative concentrations of PAF aerosols causing a 200% increase in the baseline Rrs, were 3800 +/- 604.9 micrograms/ml and 780 +/- 94.3 micrograms/ml, in the control and sensitized animals, respectively. The same magnitude of immediate bronchoconstriction after 780 and 3800 micrograms/ml of PAF exposure was observed in the actively sensitized and non-sensitized control animals, respectively. However, LAR developed 4 out of 6 animals only in the sensitized guinea pigs. We conclude that both exogenously applied PAF by inhalation and antigen exposure are capable of inducing LAR in sensitized guinea pigs, and thus the priming effect of immunization and PAF may contribute to the development of LAR observed in asthma. PMID- 1520070 TI - [A study of opioid peptides in synovial fluid and synovial tissue in patients with rheumatoid arthritis]. AB - Authors have often experienced that psychological stress influences rheumatoid arthritis (RA). In addition, recent reports show a modulatory role for neuropeptide such as substance P in arthritis. These findings prompted us to study endogenous opioid peptides in RA, which are found mainly in the brain and have an effect on the central nervous system. We examined methionine-enkephalin (Met-enk), leucine-enkephalin (Leu-enk) and beta-endorphin (beta-end) in opioid peptides. We measured these peptides in plasma and synovial fluid samples obtained from 28 knees of 24 RA patients and the quantity in the synovial tissue of 13 knees. We also measured plasma and synovial fluid samples from patients with osteoarthritis of the knee and plasma samples from healthy candidates. Leu enk and beta-end levels in synovial fluid were significantly higher than plasma levels only in RA. Larger quantity of Leu-end and beta-end were contained apparently in the synovial tissue than Met-enk. The synovial tissue with proliferative change tends to contain larger quantity of opioid peptides. These results indicate that the synovial tissue produces or secretes Leu-enk and beta end and that opioid peptides are related to the degree of inflammation in RA. PMID- 1520071 TI - Increased serum levels of soluble interleukin 2 receptor in patients with drug induced allergic hepatitis. AB - Soluble interleukin 2 receptor (sIL2R) level in the serum of 10 patients with drug-induced allergic hepatitis (DIAH) were quantified with a solid-phase enzyme immunoassay using two monoclonal antibodies against the receptor. The sIL2R levels in patients with DIAH were significantly higher than in 15 normal subjects (p less than 0.01). The high sIL2R levels observed during the florid stage of DIAH returned to normal during convalescence (p less than 0.05). SIL2R from the serum of DIAH patients was found to bind to a recombinant IL2 affinity column. It seems likely that sIL2R inhibits the hyper-immune reaction that occurs in drug allergies due to bind IL2. But, we have no data that sIL2R inhibits actually the biological activity of IL2. PMID- 1520072 TI - HDL does not promote cholesterol efflux from macrophages of hypercholesterolemic rabbit: efflux differences between species. AB - The purpose of this study was to investigate the difference between species (mouse and rabbit) and the effect of hypercholesterolemia on the ability of their peritoneal macrophages to release unesterified cholesterol to an exogenous acceptor. The macrophages from mouse, normocholesterolemic rabbits and hypercholesterolemic rabbits (Mm, Mnr, Mhr) were loaded with cholesterol esters by incubation with oxidatively modified low density lipoprotein or plasma lipoprotein (beta-migrating very low density lipoproteins). When human HDL was used as cholesterol acceptor for 24 h of incubation, the Mm Cells, the Mnr cells and Mhr cells retained about 40%, 70%, and more than 90% of their cholesterol esters. The difference between species of lipoproteins were not effective for the ability to release cholesterol esters. ACAT (acylcoenzyme A: cholesterol acyltransferase) inhibitor 58-035 increased these capacities. These data suggest that the limited capacity of macrophages from hypercholesterolemic rabbits to release cholesterol may be related to the progression and resistance to regression of atherosclerosis, and that ACAT activity might influence this capacity. PMID- 1520073 TI - Effect of a low calcium intake on the vascular sensitivity to angiotensin II in normotensive pregnant rats. AB - Vascular responsiveness to angiotensin II in pregnant rats with a normal or a low calcium diet were examined. From day 6 of pregnancy, Wistar rats were separated into two groups. One group was fed a normal diet containing 1.2% calcium (control group) and the other group was fed a low calcium diet containing 0.02% calcium (low Ca group). Using a tail cuff method, the systolic blood pressure in the low Ca group was found to be significantly higher than that in the control group on day 18 of pregnancy. On days 12 and 18 of pregnancy using the hindquarters perfusion technique, the vascular response to bolus angiotensin II (30, 100, 300, and 1000 ng/kg of rat body weight) in the low Ca group increased significantly more than that in the control group. However, the pressor response to norepinephrine and the depressor response to acetylcholine did not differ between the low Ca group and the control group. Urinary sodium excretion in the low Ca group was lower than that in the control group on days 12 and 18 of pregnancy, and decreased toward term, whereas urinary phosphorus excretion in the low Ca group was higher than that in the control group on days 12 and 18 of pregnancy. These data indicate that low calcium intake during pregnancy increases sensitivity to the pressor effects of angiotensin II and increases systolic blood pressure in normotensive pregnant rats. PMID- 1520074 TI - Peptidergic nerve involvement in the control of endothelium-dependent vascular relaxation. AB - The ability of Acetylcholine (ACh) and A23187 to induce endothelium-dependent relaxation was compared in the isolated perfused mesenteric arterial bed of untreated adult rats, adult rats treated neonatally with capsaicin, and adult rats treated as adults with capsaicin. Following neonatal capsaicin treatment, the response to both agents was reduced. Following adult treatment, the response to both agents was reduced seven days following capsaicin treatment. The same results were obtained in the presence of L-arginine or indomethacin. Tissues from all rats responded equally to sodium nitroprusside. Following capsaicin treatment no change in the structural relationship of the arterial intima was detected but no perivascular nerve fibres immunoreactive to substance P (SP) or calcitonin gene-related peptide (CGRP) could be demonstrated. It is suggested that the reduced response to ACh and A23187 does not involve a change in endothelial muscarinic receptors or a structural change in the arterial intima, but is directly related to the absence of immunohistochemically demonstrable CGRP/SP containing perivascular innervation. PMID- 1520075 TI - Oral heparin prevents hypertension and elevated cytosolic calcium in salt sensitive rats. AB - This study examined the effect of oral heparin on systolic blood pressure, platelet cytosolic free calcium, aortic calcium uptake and renal vascular changes in Dahl salt-sensitive (DS) rats on low (0.4% NaCl) and high (8% NaCl) salt diet. Twenty-four male DS rats, age 8 weeks, were divided into four groups of 6 animals each. Groups I and II were on low salt diet and groups III and IV on the high salt diet. Additionally, groups I and III were placed on 100% H2O and groups II and IV on sodium heparin 0.5 mg/ml in H2O as their drinking water for a period of 6 weeks. At 14 weeks, systolic blood pressure, platelet cytosolic free calcium and aortic calcium uptake were significantly higher in rats on high salt diet and water compared with rats from all other groups. Oral heparin treatment prevented the increase in systolic blood pressure, platelet cytosolic free calcium and aortic calcium uptake in rats on high salt diet. Heparin also prevented or attenuated the onset of adverse renal vascular changes observed in Dahl salt sensitive rats on high salt diet. Oral heparin treatment did not cause abnormal hematological, biochemical or pathological changes in rats. PMID- 1520076 TI - Circadian variation in stroke. PMID- 1520077 TI - Lyme disease revisited. PMID- 1520078 TI - A large New England kindred with autosomal dominant neurogenic scapuloperoneal amyotrophy with unique features. AB - We describe a large New England kindred bearing an autosomal dominant syndrome of neurogenic amyotrophy with variable expression. Features include congenital absence of muscles, progressive scapuloperoneal atrophy, laryngeal palsy, and progressive distal weakness and atrophy. The pattern of expression and progression varies in different branches of the family. Males are more severely affected than females. Disease expression is more severe and progressive in succeeding (third and fourth) generations. This striking increase in severity and progressivity in succeeding generations may have genetic implications. The syndrome most resembles the Stark-Kaeser chronic scapuloperoneal amyotrophy, but is considered a distinct entity. PMID- 1520079 TI - Severity of vascular dementia is related to volume of metabolically impaired tissue. AB - The relation between dementia severity and regional cerebral metabolic rate of glucose was studied in 28 patients with vascular dementia (VD) in comparison with 20 age-matched patients who were suffering from Alzheimer's disease (AD) and 24 normal subjects by using positron emission tomography with fludeoxyglucose F 18. Similar metabolic impairment was found in the temporoparietal and frontal association cortex in patients with VD and in those with AD. Metabolism of the basal ganglia, thalamus, and cerebellum was reduced significantly in patients with VD only. The total volume of regions with metabolism below the 95% confidence interval of control values was significantly related to the severity of dementia but did not differ between patients with VD and those with AD. A metabolic ratio of regional cerebral glucose metabolism of association areas divided by regional cerebral glucose metabolism of structures that were typically not affected by AD was significantly lower in patients with AD than in those with VD. This ratio was also related to dementia severity in both types of dementia. PMID- 1520080 TI - Interrelations between migraine and tension-type headache in the general population. AB - In a cross-sectional epidemiological survey of a general population, headache disorders were diagnosed according to a structured interview and a neurological examination using the criteria of the International Headache Society. The prevalences and sex distribution of the primary headache disorders were assessed, and characteristics of and interrelationships between different types of headache were analyzed. Severity and frequency of migraine attacks were not correlated, indicating that the migraine attack is an all-or-none phenomenon triggered with an individually variable threshold. Tension-type headache, in contrast, showed increasing severity with increasing frequency, indicating that it is a graded phenomenon. In the previous year, 6% had migraine without aura (previously called "common migraine") and 4% had migraine with aura (previously called "classic migraine"); 63% had episodic tension-type headache and 3% chronic tension-type headache. In women, migraine without aura was twice as prevalent as migraine with aura; in men, an opposite trend emerged. In migraine without aura, pain was more severe than in migraine with aura. Tension-type headache in migraineurs was not significantly more prevalent than in nonmigraineurs and, except for greater frequency and severity, it did not deviate nosographically from pure tension-type headache. Our results support the contention that migraine and tension-type headache are distinct entities, contradict the so-called continuum-severity model, and indicate that the terms combination headache, mixed headache, and interval headache should be avoided. PMID- 1520081 TI - Increased sympathetic and decreased parasympathetic cardiac innervation in patients with Alzheimer's disease. AB - To assess whether Alzheimer's disease affects the sympathetic and parasympathetic influences on the heart rate, we used power spectrum analysis of heart rate variability derived from simple body-surface electrocardiography. We calculated the energy ratio of low- to high-frequency bands. This ratio was significantly higher in patients with Alzheimer's disease than in normal controls (upright posture, 0.41 +/- 0.21 vs 0.23 +/- 0.08). The parasympathetically mediated baroreceptor activity reflected by the energy ratio of medium- to low- and high frequency bands was significantly depressed in patients with Alzheimer's disease (upright posture, 0.12 +/- 0.02 vs 0.07 +/- 0.03; supine posture, 0.11 +/- 0.02 vs 0.085 +/- 0.025). Compared with normal volunteer controls, patients with Alzheimer's disease manifested a relatively hypersympathetic, hypoparasympathetic state. PMID- 1520082 TI - An antispasticity effect of threonine in multiple sclerosis. AB - To determine whether the naturally occurring amino acid threonine, a potential precursor for glycine biosynthesis in the spinal cord, has an effect on spasticity in multiple sclerosis, 26 ambulatory patients were entered into a randomized crossover trial. Threonine administered at a total daily dose of 7.5 g reduced signs of spasticity on clinical examination, although no symptomatic improvement could be detected by the examining physician or the patient. In contrast to the side effects of sedation and increased motor weakness associated with antispasticity drugs commonly used for the treatment of multiple sclerosis, no side effects or toxic effects of threonine were identified. Levels of threonine were elevated in serum and cerebrospinal fluid during treatment, but glycine levels did not change. Enhancement by threonine of glycinergic postsynaptic inhibition of the motor reflex arc in the spinal cord may represent a non-sedating, nontoxic approach to the management of spasticity in multiple sclerosis. PMID- 1520083 TI - Clinical diagnosis of Alzheimer's disease and other dementias in a population survey. Agreement and causes of disagreement in applying Diagnostic and Statistical Manual of Mental Disorders, Revised Third Edition, Criteria. AB - In a population survey aimed to detect cases of Alzheimer's disease and other dementias, two preliminary diagnoses were made independently with the purpose of using the concordant diagnoses as final diagnoses. Diagnostic and Statistical Manual of Mental Disorders, Revised Third Edition, diagnostic criteria were followed. The 668 subjects examined were selected from the population of an area in Stockholm, Sweden, aged 75 years or more, with the Mini-Mental State Examination used as a screening test. The agreement on dementia diagnosis was moderate (kappa = .54) and could be clearly improved (kappa = .70) with modifications to the diagnostic criteria, such as adding a category of questionable dementia and giving more guidelines in the definition of impairment of a function. The agreement on the diagnosis of Alzheimer's disease vs vascular dementia vs secondary dementia was substantial (kappa = .67) when the cases with concordant dementia diagnoses were examined. PMID- 1520084 TI - The role of dominant premotor cortex and grapheme to phoneme transformation in reading epilepsy. A neuroanatomic, neurophysiologic, and neuropsychological study. AB - We studied a 24-year-old man who had reading epilepsy after removal of a left frontal arteriovenous malformation. Lesion analysis by means of a neuroanatomic template placed a 2-cm region of encephalomalacia anterior to the left central sulcus in premotor cortex (Brodmann's area 6). Lexical and nonlexical reading activation tests demonstrated seizures during reading and increased discharge rates when the patient was reading aloud or silently articulating. Seizures (perceived or actual jaw clicking) were electrographically characterized by brief left frontocentral epileptiform transients. Grapheme to phoneme transformation, not linguistic complexity, appears to be the critical stimulus in some reading epilepsies. The case adds anatomic relevance to the phonologic component of reading and supports the putative role of dominant premotor cortex in activation of precise sequences of motor linguistic output in reading and writing. Reading epilepsy may be a reflex or action myoclonus syndrome localized to Brodmann's area 6 (Exner's area). PMID- 1520085 TI - Absence of Lyme borreliosis among patients with presumed Bell's palsy. AB - In a prospective study, 69 patients with a presumed idiopathic (Bell's) peripheral facial palsy were clinically and serologically evaluated for the presence of Lyme borreliosis. In addition, their clinical spectrum was compared with clinical manifestations collected retrospectively in nine patients with symptomatic peripheral facial palsy due to Lyme borreliosis. The seroprevalence of Borrelia burgdorferi antibodies, determined by flagellum enzyme-linked immunosorbent assay, among 69 patients with idiopathic peripheral facial palsy (6%) and 153 healthy controls (4.5%) was not significantly different (odds ratio, 1.28; 95% confidence interval, 0.27 to 5.25). None of the patients with idiopathic peripheral facial palsy had or experienced the development of Lyme borreliosis. All patients with Lyme peripheral facial palsy had additional manifestations not present in patients with idiopathic peripheral facial palsy. These findings show that patients with a Lyme peripheral facial palsy can be differentiated from patients with idiopathic peripheral facial palsy by clinical examination. Therefore, screening of antibodies to B burgdorferi among patients with idiopathic peripheral facial palsy without additional manifestations is not recommended. PMID- 1520087 TI - Oculomotor, auditory, and vestibular responses in myotonic dystrophy. AB - In 13 patients with myotonic dystrophy, oculomotor, auditory, and vestibular tests were performed. All 13 patients showed one or more abnormalities. There was a significant increase in the penetrance of the separate abnormalities with age. Saccadic slowing was found in 10 patients, in a severe form in three. Seven patients had a sensorineural high-tone hearing loss (30 to 85 dB at 8 kHz), which was in excess of that expected for their age, that could be attributed to myotonic dystrophy. Brain-stem auditory evoked potentials showed a significant interwave delay of the I-V interval (0.35 to 0.7 milliseconds). An abnormal vestibulo-ocular reflex was found in six patients; three had vestibular hyperreflexia with increased gain, and three had hyporeflexia with short time constants. This study confirms that in myotonic dystrophy, sensory system involvement can be found on both a peripheral and a central level. PMID- 1520086 TI - Evidence for early vulnerability of the medial and inferior aspects of the temporal lobe in an 82-year-old patient with preclinical signs of dementia. Regional and laminar distribution of neurofibrillary tangles and senile plaques. AB - Detailed neuropathologic studies of neurofibrillary tangle and senile plaque distribution have shown that key elements of certain neocortical and hippocampal circuits are either compromised or lost in Alzheimer's disease. It has been suggested that a global corticocortical disconnection underlies dementia and leads to the dramatic disruption of integrated functions exhibited by patients with Alzheimer's disease. To investigate the distribution of lesions associated with the earliest indications of incipient dementia, we performed a quantitative neuropathologic evaluation of a non-demented 82-year-old patient demonstrating globally intact intellectual function but initial signs of impairment of specific cognitive functions before death. We observed densities of senile plaques comparable to those found in Alzheimer's disease throughout the cerebral cortex, whereas extensive neurofibrillary tangle formation was restricted to selective areas of the temporal lobe. The results of this systematic quantitative and comparative analysis of medial and inferior temporal lobe structures suggest a functional relationship between the degree of cognitive decline evidenced in the earliest stages of Alzheimer's disease and the anatomic progression of Alzheimer's disease-related pathologic changes along specific elements of the cortical circuitry. PMID- 1520088 TI - Neurocysticercosis and human immunodeficiency virus infection. A possible association. AB - We present four patients with active neurocysticercosis and human immunodeficiency virus type 1 infection. In three patients, symptoms of neurocysticercosis brought the patient to medical attention and led to the diagnosis of human immunodeficiency virus infection. Neurocysticercosis should be considered in human immunodeficiency virus-infected persons who have been in areas where cysticercosis is endemic. PMID- 1520089 TI - Progressive amusia and aprosody. AB - We report a case of slowly progressive amusia and aprosody in association with orofacial and eyelid apraxias. The patient was independent in daily living activities. Insight, judgment, and behavior were intact. Her language was normal, and she demonstrated no limb, dressing, or constructional apraxia. She had no prosopagnosia, no visuospatial disturbances, and no memory impairment. Imaging studies (computed tomography, magnetic resonance imaging, single photon emission computed tomography) indicated a selective disorder of the right frontal and temporal regions. Review of the literature shows an increasing number of reports of this degenerative syndrome affecting the left dominant hemisphere and language areas, whereas cases of the syndrome affecting the right hemisphere are rare. To our knowledge, this is the first case in which aprosody and amusia were associated with a focal cortical degeneration. PMID- 1520090 TI - Dissociation of color from object in amnesia. AB - A patient with persistent amnesia after bilateral medial temporal and left inferotemporo-occipital infarction could not match colors to objects in verbal, visual, or visuoverbal tasks. A severe naming disorder for objects was present but the patient could name colors and point to colors whose name was given. The matching disorder appeared to be a deficit in the semantic classification of objects rather than a problem in identifying colors. PMID- 1520091 TI - Inhibition of human subgingival plaque protease activity by chlorhexidine. AB - Subgingival plaque samples from three discrete sites in each of eight patients with adult chronic periodontitis were used to determine the ability of 0.001, 0.01, 0.1 and 1.0 mM chlorhexidine to inhibit bacterial proteolytic activity. This activity was measured by monitoring the increase in relative fluorescence (excitation and emission wavelengths of 495 and 525 nm, respectively) accompanying the degradation of fluorescein isothiocyanate (FITC)-labelled bovine serum albumin or FITC-labelled transferrin. Chlorhexidine at concentrations of as low as 0.01 mM inhibited the proteolytic degradation of both substrates by more than 50%. As the growth of dental plaque bacteria is dependent upon the liberation of nutrients (amino acids, peptides and carbohydrates) from host derived macromolecules, similar effects in vivo might explain the ability of chlorhexidine to inhibit plaque formation at subminimal inhibitory concentrations. PMID- 1520092 TI - Side asymmetry of the jaw jerk in human craniomandibular dysfunction. AB - The jaw jerk elicited by tapping the chin with a reflex hammer was electromyographically recorded in 14 patients with craniomandibular dysfunction, who were selected because of their strictly unilateral symptoms. Mandibular deviation, as measured by means of a kinesiograph, was on the same side as the pain. Neurological and neurophysiological investigations, including the recording of masseter motor potentials evoked by transcranial stimulation, showed normal function of the sensory and motor trigeminal nerve fibres. Latency and amplitude of the jaw jerk recorded in postural position and intercuspal occlusion were, respectively, longer and smaller on the affected side. In some cases the latency difference exceeded 1 ms, the limit usually considered significant for trigeminal neuropathy or brainstem lesions. Jaw-jerk asymmetry is probably due to facilitation on the side contralateral to mandibular deviation. In intercuspal occlusion, contralateral facilitation might be produced by a stronger input from muscle spindles and periodontal mechanoreceptors. In postural position, other factors probably intervene. PMID- 1520093 TI - Development of the rabbit craniomandibular joint in association with tooth eruption. AB - The adult rabbit craniomandibular joints (CMJs) are stress-bearing joints. The two CMJs and the teeth form an articular triad. In early fetal life the developing triad consists of the CMJ primordia, the tooth germs for the entire set of deciduous teeth, as well as the posterior extensions of the dental lamina, which will give rise to the permanent teeth with no deciduous predecessors. During postnatal life, before occlusion is established, there is a remodelling stage in which the CMJ builds up its matrix components such as collagenous and elastic fibres, proteoglycans and type II collagen. Remodelling gradually diminishes into the maintenance stage once occlusion is fully established and after eruption of the first and second molars. Chondrocytes first appear in the CMJ articular disc during the second week of postnatal development. These cells localize in the band areas of the disc and establish an extensive cartilaginous matrix 3-4 weeks postnatally. This study supports the concept that the full development of a fibrocartilaginous articular disc, rich in proteoglycans, occurs as adult occlusion is established. PMID- 1520094 TI - Purification and partial characterization of analogous 26-kDa rat submandibular and parotid gland integral membrane phosphoproteins that may have a role in exocytosis. AB - Rat submandibular and parotid gland exocytosis is primarily controlled by beta adrenergic receptor stimulation. Although its precise role in the regulation of salivary gland exocytosis is not fully understood, protein phosphorylation, mediated by the activation of cAMP-dependent protein kinase, may be directly involved. Previous studies suggest that analogous 26-kDa integral membrane phosphoproteins may play a direct role in regulating exocytosis. Studies were here undertaken to purify and partially characterize both phosphoproteins. After endogenous phosphorylation with 32P, subcellular fraction and solubilization of the microsomal fraction in n-octyl beta-glucopyranoside, the 26-kDa integral membrane phosphoproteins were purified by high performance liquid chromatography (HPLC), followed by sodium dodecyl sulphate-polyacrylamide gel electrophoresis and electroelution of the proteins. Amino acid analysis indicated a significant number of serine amino acids: N-terminal sequence data demonstrated a high level of homology; and trypsin digestion followed by reversed-phase HPLC indicated the possibility of multiple phosphorylation sites. PMID- 1520095 TI - Na+ influx mechanisms in submandibular salivary cells of newborn rats. AB - Uptake of this isotopic tracer was essentially the same as in cells derived from salivary glands of adult animals, both in the absence and in the presence of 1 microM acetylcholine, 10 microM monensin or 10 microM A23187. Tracer accumulation in resting cells was inhibited in the immature cells by 1 mM amiloride but the inhibition was significantly smaller than in fully mature cells (16 and 33%, respectively). Bumetanide inhibited tracer uptake by 28% in mature cells not exposed to agonist, but had essentially no effect in those of newborn rats. The tracer content of adult cells exposed to acetylcholine in Ca(2+)-free incubation solutions was significantly reduced when compared to that of cells exposed to agonist in solutions containing 1.0 mM CaCl2. A similar but significantly smaller reduction in tracer content was observed in cells of newborn animals incubated in the Ca(2+)-free medium. The inhibition of 22Na uptake observed in the presence of amiloride was the same in both types of cells in the presence or absence of external Ca2+. The findings suggest that Na entry into immature salivary cells of newborn rats is quantitatively similar to that in mature cells, but that the contribution of the loop diuretic-sensitive co-transporter and of the amiloride sensitive Na/H exchange to Na+ entry is less in the immature cells. Na entry in the immature cells is likely to occur, therefore, primarily by other mechanisms such as Ca(2+)-regulated channels. PMID- 1520096 TI - Masseteric facilitation induced by electrical stimulation of rat orofacial tissues. AB - The effects of a conditioning electrical shock applied to the periodontium of the lower incisor or the glabrous area of the lower lip on the jaw-closing reflex in the anesthetized, non-paralysed rat were studied. The masseteric reflex was triggered by stimulation of the mesencephalic nucleus as a test shock and was recorded from the masseter muscle. There was facilitation of the jaw-jerk reflex, which culminated at an interval of 10-15 ms between the conditioning and the test shocks. This facilitation was not suppressed by digastric excision or by blocking a possible rebound closing reflex evoked by jaw opening. No inhibitory influence was observed. This facilitatory effects relies on an A alpha input and on cell bodies making up the mesencephalic nucleus. The direct excitatory electrical events observed in the masseter muscle after periodontal or labial stimulation proved to be due to the diffusion of the bioelectrical activity generated in the neighbouring jaw-opening muscles. PMID- 1520097 TI - Surgical options in high-risk patients. PMID- 1520098 TI - Spontaneous improvement of progressive anterior ischemic optic neuropathy: report of two cases. PMID- 1520099 TI - Genetic spontaneous late subluxation of the lens previously reported as a myopic kinship with primary angle closure glaucoma. PMID- 1520100 TI - Protective eyewear needed with driver's-side air bag? PMID- 1520101 TI - Uveal effusion syndrome: visual field and electroretinographic changes in correlation with shifting subretinal fluid. PMID- 1520102 TI - Magnetic resonance imaging of leukemic invasion of the optic nerve. PMID- 1520103 TI - Familial posterior lenticonus and microcornea. PMID- 1520104 TI - Physicians provide $6.8 billion in charity care. PMID- 1520105 TI - Excimer laser photoablation. Clinical results and treatment of complications in 1992. PMID- 1520106 TI - Trends in the ophthalmic literature, 1949-1989. AB - Trends in the ophthalmic literature were analyzed through five decades of the Archives. Original articles from 1949, 1959, 1969, 1979, and 1989 were reviewed. The mean number of authors per article increased steadily from 1.24 in 1949 to 3.50 in 1989. The mean number of institutions per article increased from 1.04 in 1949 to 1.30 in 1989. The mean number of authors with a doctor of philosophy degree increased from 0.03 per article in 1949 to 0.41 in 1989. Financial support increased from 13.5% of manuscripts in 1949 to 62.6% in 1989. These findings emphasize the growing trend in the ophthalmic literature toward multiple authors, multiple institutions, collaboration with basic scientists, and increased reliance on grant support. PMID- 1520108 TI - Repeated excimer laser treatment after photorefractive keratectomy. AB - Scarring or undercorrection occurs in a small percentage of patients after myopic photorefractive keratectomy. Scarring occurred in 1.8% of 298 patients with a baseline myopia of 6.0 diopters or less, increasing to 8.8% in those with corrections of more than 6.0 D. Undercorrection of more than 1 D occurred in 2.7% of the eyes with a baseline myopia of up to -6.0 D. A much greater incidence of undercorrection (30% to 40%) was found after corrections of more than 6.0 D. Thirty eyes in 30 patients were reoperated because of scarring (11 eyes) and/or undercorrection (27 eyes) and were observed for 6 to 18 months (average, 7.8 months). Only one of the eyes has shown mild scar formation after this second laser treatment. Sixty-three percent of these patients had a manifest refraction between -1.0 D and +1.0 D six months after reoperation. Repeated phototablation seems to be a valuable technique for treatment of undercorrection and/or scarring after photorefractive keratectomy. PMID- 1520107 TI - Statistical techniques in ophthalmic journals. AB - Over the years, the use of statistics to evaluate experimental data in ophthalmology has increased. The present study sought to assess the frequency and types of statistical techniques used in ophthalmic journals. We reviewed 974 original articles from the Archives for 1970, 1980, and 1990; the American Journal of Ophthalmology for 1990; and Ophthalmology for 1990. Of the 592 articles reviewed for 1990, 391 (66.0%) contained statistics, with measures of central tendency most commonly used (385 articles [65.0%]), followed by dispersion (298 [50.3%]), t test (120 [20.3%]), and contingency tables (98 [16.6%]). A reader familiar with 10 statistical techniques would have "statistical accessibility" to 526 (88.9%) of 1990 articles. A statistically significant difference was found in the percentage of articles containing statistical methods among the journals (P = .0003; Archives, 75.3%; Ophthalmology, 66.8%; and American Journal of Ophthalmology, 55.2%). PMID- 1520109 TI - Ofloxacin vs tobramycin for the treatment of external ocular infection. Ofloxacin Study Group II. AB - A multicenter, double-masked, randomized clinical investigation was conducted comparing 0.3% ofloxacin and 0.3% tobramycin for topical treatment of external ocular infection. One drop (1.35 micrograms) of either test solution was instilled six times daily for 2 days and thereafter four times daily for the next 8 days. At the day 3 to 5 follow-up examination, the severity of signs and symptoms based on a clinical summary score of 10 key variables was reduced from baseline values significantly (P less than .05) more with ofloxacin (-6.4 +/- 4.37; mean +/- SD) than with tobramycin (-4.78 +/- 3.13); by day 11, the difference between the groups was no longer significant. At days 3 to 5 and day 11 examinations, clinical, microbiologic, and overall improvement rates were similar, with no significant differences seen between the groups. Ofloxacin was found as effective, safe, and comfortable as tobramycin in patients with external ocular infection and may provide earlier symptom relief. PMID- 1520110 TI - Subconjunctival cysts as a complication of strabismus surgery. AB - Six patients were operated on for large subconjunctival cysts that developed up to 35 years after strabismus surgery. In four of these patients the cyst was found to arise between the anterior edge of the muscle and the site to which the muscle had been sutured during previous surgery. The muscle was attached to the posterior wall of the cyst and not to the sclera. A pseudotendon was found running between the point on the sclera to which the muscle had been sutured and the undersurface of the muscle far posteriorly. In the other two patients a sudoriferous cyst was found that the referring ophthalmologist had mistakenly thought to represent an abscess when excision was attempted. PMID- 1520111 TI - Comparison of the double-plate Molteno drainage implant with the Schocket procedure. AB - A randomized, prospective study was undertaken to compare the results of the double-plate Molteno implant with those of the anterior chamber tube shunt to encircling band (ACTSEB) procedure, described by Schocket, for eyes with complicated glaucoma. One surgeon performed all the procedures. For statistical analysis there were 21 eyes in the ACTSEB group and 19 eyes in the Molteno group, with at least 6 months of follow-up (mean follow-up, 26 months; range, 6 to 49 months). Eyes with aphakia/pseudophakia, uveitis, previous penetrating keratoplasty, previous unsuccessful trabeculectomy, and neovascular glaucoma were evenly distributed between the two groups. Mean preoperative intraocular pressures in the ACTSEB and Molteno groups were 35.2 and 34.6 mm Hg, respectively. With the exclusion of one phthisical eye in each group final mean intraocular pressure in the ACTSEB group was 15.1 mm Hg, with a mean of 0.43 medications, and 14.4 mm Hg, with a mean of 0.95 medications, in the Molteno group. Seven (33%) of 21 eyes and 13 (68%) of 19 eyes in the ACTSEB and Molteno groups, respectively, were receiving additional antiglaucoma medication at the most recent visit (P = .027). Final visual acuity was stable (within one Snellen line of baseline visual acuity) or improved in 10 (48%) of 21 eyes in the ACTSEB group compared with 13 (68%) of 19 eyes in the Molteno group. Complications or inadequate pressure control requiring further surgical intervention were seen in nine (47%) of 19 eyes in the Molteno group and 12 (57%) of 21 eyes in the ACTSEB group.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1520112 TI - Diffuse unilateral subacute neuroretinitis in South America. AB - We describe two cases of diffuse unilateral subacute neuroretinitis in South America. These Brazilian patients presented with subretinal worms similar in size to those described in the southeastern United States. This is the first report, to our knowledge, of diffuse unilateral subacute neuroretinitis occurring outside the United States and Caribbean Islands. PMID- 1520113 TI - Observations on patients with idiopathic macular holes and cysts. AB - We reexamined 96 patients with macular holes or cysts. The mean follow-up period was 4.7 years. Of 19 eyes with macular cysts, only two (10.5%) showed progression to a macular hole. In 15 (79%) of those 19 eyes, the cyst disappeared. Of 80 patients with a macular hole or cyst in one eye and a normal fellow eye, a hole developed in the fellow eye in only one patient (1.2%) and a cyst developed in the fellow eye in only two patients (2.5%). Of 66 eyes with a stage 3 full thickness macular hole, three eyes (5%) showed resolution without any sign of a hole. Our results suggest a favorable prognosis for normal fellow eyes of patients with macular holes or cysts and for eyes with cysts. Eyes with full thickness macular holes have a less favorable prognosis, although their natural history may not be as poor as previously thought. PMID- 1520114 TI - A long-term follow-up of metallic intraocular foreign bodies, employing diagnostic x-ray spectrometry. AB - We describe 10 eyes harboring metallic intraocular foreign bodies (IOFBs) for 9 to 46 years that had undergone diagnostic x-ray spectrometry to measure metal dissolution 9 years before this study. Findings from the present clinical and laboratory examinations, including perimetry, electroretinography, electrooculography, and diagnostic x-ray spectrometry examinations are reported. Deterioration in visual acuity consequent to metal dissolution of the IOFB was found in only one eye. Visual fields and electrophysiologic performances deteriorated in two other eyes for reasons that were probably unrelated to IOFB dissolution. Visual functions remained stable during the follow-up period in seven eyes, although excess copper levels were demonstrated in one of them. Eight of 10 eyes retained visual acuity of 6/24 or better. Diagnostic x-ray spectrometry confirmed siderosis in one patient and ruled out metallosis in the two patients with deteriorated vision for reasons that were unrelated to metallosis. The favorable outcome of this series of patients may influence one to consider a more conservative approach in the decision to remove IOFBs. A careful, life-long follow-up might be considered with periodic electroretinographic and diagnostic x-ray spectrometry examinations; the IOFB should be promptly removed if and when metallosis with damage to visual functions is demonstrated. PMID- 1520115 TI - 'Black cornea' after long-term epinephrine use. AB - Fifteen years after a partial maxillectomy and radiation therapy for left antral carcinoma, a 53-year-old woman presented to the Eye Plastics and Orbit Service of the Massachusetts Eye and Ear Infirmary, Boston, with phthisis and a large, black corneal lesion in the left eye. She had been treated for unilateral glaucoma in the left eye for more than 10 years with topically administered epinephrine borate, timolol maleate, and pilocarpine hydrochloride. Clinically, the lesion was smooth, black, and homogeneous, and was thought to represent uveal prolapse covered by a thin layer of epithelium. An eyelid-sparing anterior exenteration was performed. Histopathologic examination revealed an acellular, homogeneous substance that stained positively with the Fontana Masson stain for melanin and bleached with potassium permanganate, findings consistent with corneal adrenochrome deposition. Since adrenochrome can be easily dissected free from the cornea, this case illustrates that misdiagnosing adrenochrome deposition may lead to unnecessary surgery. PMID- 1520116 TI - Progressive enlargement of a circumscribed choroidal hemangioma. A clinicopathologic correlation. AB - A man with a circumscribed choroidal hemangioma was followed up for almost 10 years as the tumor showed gradual, progressive enlargement in both diameter and thickness. In spite of photocoagulation therapy, a total retinal detachment and blindness ensued. Enucleation was performed because the possibility of amelanotic choroidal melanoma could not be absolutely excluded. Although the tumor thickness measured by ultrasonography before enucleation was 4.5 mm, the lesion measured only 2.0 mm in thickness in the pathology laboratory. Circumscribed choroidal hemangioma rarely demonstrates clinical evidence of growth. It appears that the tumor enlargement noted in this case was due to venous congestion in the tumor and not to cell multiplication. PMID- 1520117 TI - Assessment of visual acuity via a telephone interview. AB - We compared the visual acuity of 89 patients obtained via a telephone interview with visual acuity elicited from the same patients in an ophthalmologist's office. Agreement within one line of vision between the telephone interview, in which patients used a modified Rosenbaum near card with attached patch, and the clinic near vision test was observed in 91% of eyes, while agreement within one line of vision between the telephone interview and clinic distance vision test was found in 86% of eyes. We conclude that testing visual acuity via a telephone interview is a potentially useful approach to assessment of visual acuity and prevalence of visual impairment in the larger population. PMID- 1520118 TI - Corneal wound healing in monkeys after repeated excimer laser photorefractive keratectomy. AB - Five rhesus monkey eyes underwent repeated argon fluoride (193 nm) excimer laser myopic photorefractive keratectomy 3 months following an initial ablation that had produced mild subepithelial haze. At 3 months all eyes had development of a dense subepithelial opacity and a thickened epithelium (12 cells, 80 microns) with vacuolization of basal cells, fragmented basement membrane, and a layer of subepithelial fibrosis containing activated fibroblasts. By 6 months the opacity was clearing; epithelium was thinner (50 microns); subepithelial fibrosis was more lamellar. By 15 months only mild haze persisted clinically; epithelium was 30 microns thick, with persistent basal vacuolization and focal basement membrane disruption; subepithelial fibrous tissue was more organized. Early repeated excimer laser ablation of the monkey cornea apparently induces vigorous stromal wound healing. Use of shallower ablations, corticosteroids, or a longer delay between ablations may be necessary for repeated laser surgery to be practical clinically. PMID- 1520119 TI - Interleukin 6 facilitates corneal epithelial wound closure in vivo. AB - Rapid corneal epithelial wound healing is essential to the maintenance of clear visual acuity. The cytokine interleukin 6 is thought to participate in the wound healing process. We investigated the effect of interleukin 6 eye drops on the rate of corneal epithelial wound closure in rabbits in vivo. Recombinant human interleukin 6 in phosphate-buffered saline at concentrations of 0.1, 0.3, or 1 mg/L was administered immediately after the epithelium was debrided with the n heptyl alcohol treatment and 2, 4, 6, 8, 10, 18, 20, 22, 24, 26, and 28 hours after debridement. The eyes were stained with fluorescein and photographed at baseline and at 7, 10, 18, 21, 24, 27, 30, and 43 hours after debridement. The rate of wound healing was calculated with a linear regression analysis based on the areas of the epithelial defects, which were recorded from hour 10 to hour 30. The mean (+/- SD) healing rate in the control group, which received phosphate buffered saline alone, was 1.03 +/- 0.15 mm2/h. The administration of interleukin 6 at concentrations of 0.1, 0.3, or 1.0 mg/L increased the healing rate significantly (P less than .001) to 1.27, 1.39, or 1.44 mm2/h, respectively. Our results indicate that the administration of interleukin 6 might have clinical applications in the treatment of persistent corneal epithelial defects. PMID- 1520120 TI - Diabeteslike preproliferative retinal changes in galactose-fed dogs. AB - Retinal vessel changes were experimentally investigated by a combination of color fundus photography, fluorescein angiography, and histologic studies in beagles that were fed a 30% galactose diet for up to 66 months. Previously, we have described the appearance of pericyte ghosts, microaneurysms, acellular capillaries, and intraretinal hemorrhages in dogs fed a galactose diet for up to 36 months. These disorders were similar to those observed in humans with background diabetic retinopathy. We report herein that dogs fed galactose for 48 to 60 months experience retinal changes associated with the chronic occlusion of capillary beds and subsequent ischemia of the retina. These changes included the appearance of broad areas of nonperfusion, soft exudates (cytoid bodies), intraretinal microvascular abnormalities, occluded arterioles, preretinal and intravitreal hemorrhages, and apparent new vessel growth around the optic disc. The present study clearly demonstrates that the galactose-fed dog is an animal model in which advanced retinal changes develop, and these changes are similar to those associated with preproliferative human diabetic retinopathy. PMID- 1520121 TI - Fundus measurements with indirect ophthalmoscopy. An experimental approach. AB - We examined the factors influencing the accuracy of indirect ophthalmoscopic estimates of choroidal tumor size by studying indirect ophthalmoscope photographs of solid black domes implanted in the suprachoroidal space of postmortem human eyes. Measurements of the indirect ophthalmoscope photographs showed clinically significant differences in the absolute diameter of the visualized fundus, which varied with differences in condensing lens power and width, anteroposterior location of viewed fundus, and axial length of the experimental eye. Linear regression analysis demonstrated that the field of view of each condensing lens varied similarly with axial length and that the majority of variation in field size for each condensing lens was attributable to axial length variation. Equatorial fields of view averaged 11% smaller than posterior fields of view. The accuracy of estimated absolute intraocular dimensions using indirect ophthalmoscopy potentially approaches +/- 5%. PMID- 1520122 TI - Ocular erysipelas. PMID- 1520123 TI - Perforating ocular fishhook injury. PMID- 1520124 TI - Tying the knot. Is it always necessary? AB - Securing the final muscle position during adjustable-suture strabismus surgery is usually accomplished by tying the sutures in a knot in the early postoperative period. Even patients who have satisfactory ocular alignment without adjustment require manipulation of inflamed ocular tissues to secure the muscle. In our experience, approximately half of these cases are not adjusted. We have devised a technique in which postoperative knot tying is required only in those patients who actually undergo adjustment. In our series of 42 patients who underwent adjustable-suture surgery, 22 cases were not adjusted and 30 cases were left untied. No instances of muscle slippage occurred. We believe this reduction in postoperative manipulation represents an improvement in adjustable-suture strabismus surgery. PMID- 1520125 TI - An agenda for the College. The educational challenge ahead. PMID- 1520126 TI - The use of aerosol medication in respiratory disease. PMID- 1520127 TI - Lasers in dermatology. AB - The author gives a resume of the use of the different types of laser in dermatology and outlines the indications and usage for each one. Special emphasis is put on recent changes. PMID- 1520128 TI - Diagnostic ultrasound. AB - Significant growth in the technology and clinical application of diagnostic ultrasound has occurred over the past decade. The non cardiac aspects of these recent developments are briefly discussed and illustrated. PMID- 1520129 TI - Psychotropic medications. AB - A number of new psychotropic drugs are now available and new uses have been found for old ones. The author highlights these changes. PMID- 1520130 TI - Operative hysteroscopy and endometrial ablation. AB - Operative hysteroscopy is often an alternative to hysterectomy in the treatment of menorrhagia. The author describes the techniques involved and explores some of the advantages and disadvantages. PMID- 1520131 TI - General practice 'going places'. AB - This paper, which was presented at the Annual General Meeting of the Royal Australian College of General Practitioners in September 1991, outlines possible roles for the general practitioner in the public health system. Four fundamental steps need to be taken: affirmative action by health boards to include GPs in all activities; representation of the RACGP on health boards; adequate remuneration; and part time employment of GPs in all health care delivery service units. PMID- 1520132 TI - Obstetrics in a small maternity hospital. AB - This paper presents the case for continuing to practise safe obstetrics in a small suburban hospital. Boothville Maternity Hospital, Brisbane, is a Salvation Army hospital of 20 beds. Seven thousand births during the years 1975 to 1989 are reported. Perinatal mortality rate was 4.9/1000 total births, forceps rate 7.1%, caesarean rate 9.3% and transfer rate to larger centres 1.6% for babies and 1.2% for mothers. Personalised family-centred care in congenial surroundings serves to maximise the factors that favour uncomplicated delivery. Large centralised and small peripheral hospitals should be seen not as competitive but as complementary. Boothville provides mutually satisfying co-operation for care givers and care-receivers. PMID- 1520133 TI - General practitioner referrals to a department of emergency medicine. AB - The aim of this study was to determine the number and content of general practitioner referrals letters and telephone calls in 1000 consecutive patterns and assess the outcome for the referred patients. Communication between GPs and emergency medicine staff was of generally acceptable quality but could be improved in areas of letter content and call back to GPs by emergency medicine staff. PMID- 1520134 TI - Medical writing. A beginner's guide. AB - The author presents practical guidelines for writing a variety of medical articles. Newer forms of exposition, for example, poster presentations, are also explored. Guidelines and checklists for common grammatical problems are included. PMID- 1520135 TI - Cervical polyps. PMID- 1520136 TI - The tachycardias. PMID- 1520137 TI - Trainee research projects. AB - In this series, items contributed by others with research interests are welcome. This month I summarise a report presented to the 1991 RACGP convention in Hobart by Dr Roger Strasser, Senior Lecturer in Community Medicine at Monash University. PMID- 1520138 TI - Diarrhoea. AB - Diarrhoea is defined as the frequent passage of loose or watery stools. Most patients can easily recognise and accurately define acute diarrhoea as an abrupt change in their bowel habits. Chronic or recurrent diarrhoea is more difficult for the patient to define, since it may mean malabsorption, tenesmus or true diarrhoea. Serious disorders not to be missed include neoplasia, AIDS, various serious infections such as amoebiasis, and inflammatory bowel disease. PMID- 1520139 TI - Patient education. A healthy diet for people with diabetes. PMID- 1520140 TI - Management of angina. PMID- 1520141 TI - Injection into temporomandibular joint. PMID- 1520142 TI - Scenes from childhood. PMID- 1520143 TI - All that itches is not thrush. PMID- 1520144 TI - Appointment system. PMID- 1520145 TI - CT scan of the brain. PMID- 1520146 TI - Health care in Canada and the UK. PMID- 1520147 TI - Subungual haematomas. PMID- 1520148 TI - Re-operation for recurrent malignant brain tumours: is it worthwhile? PMID- 1520149 TI - Inaugural William Manchester Lecture. The influence of microsurgery research on plastic and reconstructive surgery. PMID- 1520150 TI - Surgical oncology and the role of regional chemotherapy. PMID- 1520151 TI - Squamous cell carcinoma of the skin of the trunk and limbs: the incidence of metastases and their outcome. AB - The incidence and outcome of metastatic squamous cell carcinoma of the skin is poorly documented. This study, undertaken in a population accessible to long-term follow-up, documents the metastatic aspects of squamous cell carcinoma of the skin of the trunk and limbs. In a review of 695 cases, metastases occurred in 34 cases, with a metastatic rate of 4.9%, an overall mortality of 3.4%, and a 70.6% mortality in the metastatic group. Forty-six per cent of overall mortality was associated with inoperable or recurrent regional disease without evidence of distant metastases. The risk factor associated with the development of metastatic disease were; delayed presentation; large neglected lesions; misdiagnosis; and multiple treatments to the primary lesions. In this series no correlation was found between the histological degree of differentiation of the primary tumour and the development of metastases. The mean latent period between treatment of the primary and the diagnosis of metastases was 11 months. Histopathological review of the regional lymph nodes in the operable group showed that adverse pathology such as multiple nodes, extracapsular spread, vascular and perineural invasion, were associated with regional recurrence and short survival. Twenty-one patients with operable metastases had a mean survival of 53.8 months. This was compared with 13 patients with inoperable disease, in whom the mean survival was 12.2 months (P less than 0.05). PMID- 1520152 TI - New concepts in radiotherapy for advanced squamous cell carcinoma of the head and neck. AB - This paper reviews two of the newer concepts - multiple daily fractions of radiotherapy - in improving the treatment of squamous cell carcinoma of the head and neck. PMID- 1520153 TI - Limitations of radiotherapy in the definitive treatment of squamous carcinoma of the tonsillar fossa. AB - Between 1970 and 1990, 104 patients with squamous cell carcinoma (SCC) of the tonsil were treated. The median age was 58 years and 80% of patients were males. Distribution among clinical stages was: stage I, 19 patients; stage II, 12 patients; stage III, 23 patients; and stage IV, 48 patients. More than 70% of patients had initial radiotherapy as definitive treatment irrespective of stage, reflecting the treatment philosophy over much of this period. The overall survival rate was 26% at 5 years, with survival being significantly affected by T stage, clinical stage and age. Clinical node status did not significantly affect survival rates. Good local control of T1N0 cancers was achieved with radiotherapy alone, but patients with more advanced cancers did poorly. We have now moved away from a non-selective policy and use initial surgery combined with postoperative radiotherapy in most patients, reserving radiotherapy alone for mainly early tonsil cancers. PMID- 1520154 TI - Colorectal cancer screening: optimal compliance with postal faecal occult blood test. AB - Five approaches to postal faecal occult blood test (FOBT) were compared in a population sample of 966 subjects collected from three general practitioner patient lists in Southern Sydney. The highest compliance rate (59.8%) was achieved by a method using a general practitioner letter, with no dietary restrictions with FOBT. This was also the least expensive method. Compliance rates can be affected by incorrect address information and screenees not considering themselves to be current patients. An explanation from the family doctor addressed personally to the patient with an enclosed FOBT kit can achieve high compliance rates. PMID- 1520155 TI - Inpatient management of piles: a surgical audit. AB - A retrospective study was performed on 160 patients admitted to the University Surgical Unit between July 1975 and November 1989 with haemorrhoidal disease. Patients' records were analysed with respect to predisposing factors, inpatient management, postoperative analgesia, hospital stay and post-management complications. One hundred and nineteen patients had haemorrhoidectomy (low ligation combined with an anal stretch). Of these, 1.6% developed urinary retention and 4.2% bled postoperatively but did not require surgical intervention. Ten patients were found to have tight anal canals post surgery and required outpatient anal dilatation. In no case was dilatation necessary for more than 3 months. Three patients required a therapeutic course of antibiotics. Of the 119 patients, 60 required narcotic analgesia for less than 24 hours. Hospital stay was 1-4 nights. PMID- 1520156 TI - Bleeding duodenal ulceration: the results of emergency treatment with highly selective vagotomy. AB - We report the results of a prospective study of all patients undergoing highly selective vagotomy (HSV) for bleeding duodenal ulceration (BDU) at Concord Hospital between 1979 and 1989. Highly selective vagotomy was undertaken in 63 patients (58 male, 5 female) with a median age of 69 years (range: 16-89). Fifty five patients were reviewed, 7 patients having died in the peri-operative period and one being lost to follow-up. The mean period to review was 50 months (range: 1-120). Thirty-six patients have been followed-up for more than 24 months. Thirty day postoperative mortality was 11% (7 patients). Combined major and minor morbidity was 41%. Postoperative rebleeding occurred in four patients (6.3%), three of whom died. Ulceration had recurred in two of 55 patients (4%). Symptoms have been evaluated in 55 patients since operation and 93% have been graded as Visick I or II. We conclude that HSV is effective in the emergency treatment of BDU and has few long-term sequelae. PMID- 1520157 TI - Changing trends in perforated peptic ulcer during the past 45 years. AB - Since 1944 there has been a dramatic change in the pattern of admissions for perforated peptic ulcer (PPU) to the Royal Newcastle Hospital, the main teaching hospital of the Hunter Region, Australia. Between 1944 and 1950, females accounted for 6% of all perforations; since then the proportion of females admitted with this complication has risen to 32%. Simultaneously, the modal age for PPU has shifted from the fifth to the seventh decade and the ratio of gastric to pyloroduodenal perforations has fallen from 1.1:1 to 0.6:1. No good explanation for this change in the natural history of PPU, also noted elsewhere, is evident. PMID- 1520158 TI - Wound closure and suturing patterns: a vector analysis of suture tension. AB - When the vectors of force required to close the ideal surgical wound are analysed, it is apparent that suture tension varies with the pattern of suture. For a given closing force, perpendicular interrupted sutures have the least tension. Symmetrical continuous sutures require greater suture tension, and this increases the more the suture is aligned with the direction of the wound. Asymmetrical (perpendicular/diagonal) continuous suturing requires more tension than interrupted sutures but this never exceeds 200%. Symmetrical suturing has slightly less tension than asymmetrical suturing when the spacing is about equal to the width of the suture. However, as the spacing ratio increases to greater than 2, the tension in the symmetrical suture rises very sharply. At a length:width ratio of 4, the symmetrical suture tension is about 70% greater than the same asymmetrical suturing. PMID- 1520159 TI - Ligature versus purse string for surgical stapled anastomoses. AB - Intraluminal circular stapling in gastrointestinal surgery requires a purse string suture which secures the bowel around the anvil of the head of the stapling gun before firing. An alternative method of securing the bowel around the anvil is described. PMID- 1520160 TI - Role of the pre-test in the progressive assessment of medical students. AB - A prospective, randomized, controlled trial was conducted to see if a pre-test, given immediately before teaching, improved performance in a subsequent post test. The study was also used to assess the educational value of a structured teaching method. Third year medical students were randomized into study and control groups. In phase I, the study group completed a subject-specific multiple choice question (MCQ) pre-test immediately before a teaching demonstration on vascular disorders. The control group completed a placebo pre-test. At the completion of teaching both groups did the same subject-specific post-test. The experiment was repeated in phase II where the groups were crossed over and traumatology was the subject of the demonstration. In both phases of the experiment there were no significant differences between the post-test marks of the experimental and control groups (P = 0.128 and 0.397, respectively). The experimental groups did, however, increase their marks significantly when their post-test results were compared with pre-test marks (P less than or equal to 0.0001, phase I and II). It was concluded that the pre-test did not result in a measurable increase in learning. The study did demonstrate that the teaching method was effective as post-instructional knowledge increased by nearly half when compared with pre-test levels. PMID- 1520161 TI - Prolonged hepatic ischaemia due to liver injury: a case report. AB - A case is reported in which a young male who underwent right hepatectomy necessitated by gunshot wound to the liver, survived 2 h 20 min of normothermic hepatic ischaemia. This case extends the documented duration of hepatic ischaemia compatible with survival and documents the histopathology of the post-ischaemic liver. PMID- 1520162 TI - Constrictive pericarditis associated with trauma and pectus excavatum. AB - A case of constrictive pericarditis is reported in a 31 year old man with pectus excavatum. The constriction was secondary to an organized traumatic pericardial haematoma immediately behind the pectus deformity. PMID- 1520163 TI - A bronchogenic cyst causing respiratory distress. AB - A case is reported of acute respiratory distress in an adult that was caused by a bronchogenic cyst. Bronchogenic cyst in an adult may be seen on chest X-ray and confirmed by computerized tomography (CT) scanning. Surgical excision can provide dramatic relief. PMID- 1520164 TI - Duplex Doppler ultrasound signs of portal hypertension: relative diagnostic value of examination of paraumbilical vein, portal vein and spleen. AB - The sonographic parameters in portal hypertension (PHT) were examined in a consecutive population of 118 patients who had PHT diagnosed using specific endoscopic, sonographic and Doppler signs. A patent or enlarged paraumbilical vein was found in 85.6% of patients overall and 82.5% of patients with varices indicating a relatively high sensitivity. A portal vein diameter greater than or equal to 13mm was found in only 41.1% and greater than or equal to 15mm in only 20% of patients. A thrombosed portal vein and reversed portal vein flow were present in 3.4% and 5.3% of patients respectively. These signs have only been reported in the context of PHT and are felt to be specific for PHT, but both have a very low sensitivity. Portal vein velocities were highly variable suggesting that this is not a useful predictor of PHT. Splenomegaly was found in only 53.5% of patients demonstrating its poor sensitivity as a sign of PHT. Varices were found in 73.3% of patients overall, and in 100% of patients with a patent or enlarged paraumbilical vein combined with ascites. No other statistically significant correlation between varices and sonographic findings was demonstrated. We conclude that the presence of a patent or enlarged paraumbilical vein is a practical, useful and sensitive ultrasound sign to look for in the diagnosis of PHT. PMID- 1520165 TI - Fluid collections and transposed ovaries--not always functional cysts. PMID- 1520166 TI - Efficacy of fetal part elevation to visualise internal cervical os. AB - The diagnosis or exclusion of placenta previa is best achieved by direct visualisation of the relationship of the lower edge of the placenta to the internal cervical os. In later pregnancy, the presenting fetal part frequently obscures this area. Elevation of the presenting part was attempted in 56 consecutive pregnancies of greater than 30 weeks gestation, with a success rate of 71%. This confirms that in a minority of pregnancies, other manoeuvres or ultrasound techniques are necessary to visualise the lower placental margin directly. PMID- 1520167 TI - Percutaneous lung aspiration biopsy: a comparison between two fine needles. AB - Fine needle lung aspiration biopsy is now a well established method of obtaining tissue for histopathological diagnosis. It is fast, simple and reliable, and has a very low complication rate. We report our experience using two fine needles, the Turner and the EZ-EM Cut-Biopsy needles, comparing their yield and complication rates. We found that both needles had comparable diagnostic yields (65% with the Turner, and 71% with the EZ-EM) and complication rates. We also found that in most cases, aspirates alone were sufficient for diagnosis, and that obtaining tissue cores with larger bore EZ-EM needles did not significantly influence the diagnostic outcome. We conclude that both the Turner and the EZ-EM needles are equally effective and safe in percutaneous lung aspiration biopsy. The least traumatic needle should be used except when the cytological diagnosis is nonspecific inflammatory cells or inadequate, in which case a repeat with a cutting needle is advised to obtain a core of tissue. PMID- 1520168 TI - An analysis of reported discomfort caused by mammographic X-ray amongst attenders at an Australian pilot breast screening program. AB - The aims of the study were to describe levels of discomfort experienced by women undergoing screening mammography; examine correlates of discomfort experienced and to examine whether the degree of discomfort experienced was perceived as a deterrent for re-screening. The study involved ninety five attenders at the pilot mammography screening program in Melbourne, Victoria. Women completed a questionnaire one or two days after having a screening mammogram. Pain was assessed on a seven point scale. Information was obtained on a number of possible correlates such as breast tenderness, perceptions of the service received and expectations of discomfort. Eighty-eight women were re-interviewed three months later about recall of discomfort and whether this would deter them from future mammography. Results were as follows: Thirty per cent of women reported no discomfort, 60% mild or moderate discomfort and 10% severe discomfort or worse. The degree of discomfort reported was not significantly related to age, breast tenderness in the previous three days, previous symptoms, previous mammographic experience, or outcome of visit. The degree of discomfort was related to retrospectively reported expectation of discomfort (r = .336; p = .001); reported lack of confidence in the staff taking the X-ray (r = .184; p = .039); perceptions of awkwardness (r = .175; p = .049) and unpleasantness (r = .297; p = .002) of the examination position. No woman said discomfort would definitely stop her having another screening mammogram. Three per cent said that it might stop them, while 97% of women said that it would not stop them at all.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1520169 TI - Breast pain associated with mammographic compression. AB - Firm breast compression during film-screen mammography is necessary to achieve optimum image quality while minimizing radiation dose. Of 374 women who fully completed a questionnaire following mammography, 225 (60%) reported no pain, 115 (31%) moderate pain and only 3 (1%) reported severe pain. Only one patient stated that the pain from the procedure would prevent her from having a further mammogram. Underlying breast disease (usually fibrocystic disease) is associated with a greater incidence and severity of breast pain, but, no relationship has been demonstrated with regards to the patient's age, hormonal status, menstruation or caffeine intake. The high level of acceptance of firm compression by women in our study indicates that undue concern regarding patient discomfort should not deter people from referral for mammography or from the application of firm compression. PMID- 1520170 TI - CT evaluation of orbital osseous hemangioma. AB - Two patients with osseous hemangioma of the orbit, and with typical features on plain radiography and computed tomography, are reported. The typical features of osseous hemangioma of the orbit on computerised tomography (CT) are: expansile bony lesion limited by a thin sclerotic rim, bony trabeculae radiating from the centre to the periphery of the lesion, and absence of an associated extra-tumoral soft tissue mass. To the best of our knowledge this is the first report of osseous hemangioma of the orbit evaluated by CT. PMID- 1520171 TI - Air in epidural haematomas. AB - Air in epidural haematoma is an uncommon finding. It is usually seen if epidural haematoma is associated with fracture involving one of the air sinuses, but can be seen at times in the absence of any demonstrable fracture on the CT scan. Seven such cases are described in the present communication and the significance of this finding discussed. PMID- 1520172 TI - Temporomandibular joint air in fractures of the skull base. AB - Basilar skull fractures involving the temporal bone extend through the tympanic part of the temporal bone in two-thirds of cases. The anatomical relationship of this part of the temporal bone and the temporomandibular joint enables air to pass from the auditory canal into the joint. Air in the temporomandibular joint is demonstrated on CT scans as an indirect sign of temporal bone fracture. PMID- 1520173 TI - Midshaft tibial stress fractures in children (report of four cases). PMID- 1520174 TI - Anomalous peritoneal folds of the duodenum--a normal variant simulating disease. AB - The double contrast barium meal appearance of four cases is presented where an anomalous peritoneal fold involves the duodenum. This fold results in a characteristic smooth, extrinsic indentation upon the antero-superior surface of the duodenal cap. This normal variant should be differentiated from distortion of this region due to pathology such as peptic ulceration. Anomalous peritoneal folds which involve the duodenum (cystoduodenal ligament, cysto-gastrocolic ligament) are not believed to cause symptoms (1). However, the recognition of the deformity produced by these folds is important, requiring differentiation from pathological changes. PMID- 1520175 TI - Dose normalisation and specification: from woe to go. AB - A questionnaire has been completed by 16 practising Radiation Oncologists from 10 centres in Australia and New Zealand which confirms that considerable variation in dose normalisation and specification practices exists between Australasian centres. The establishment of a working party to determine whether a uniform code of practice (such as ICRU 29 or a modification thereof) is desirable, and can be adopted in Australasia, is recommended. PMID- 1520176 TI - Anaphylactoid reaction to iopamiro (after pretreatment). AB - A patient is described with a past history of an anaphylactoid reaction to contrast media who reacted to nonionic contrast media after pretreatment with antihistamines and steroids. The available options to reduce the incidence of reactions include use of non-ionic contrast which has a reported lower frequency than ionic contrast or some form of pretreatment. Various forms of pretreatment have been described and in the majority steroids and antihistamines are used. We describe a patient who reacted to nonionic contrast after a pretreatment regime. PMID- 1520178 TI - Intracerebral ganglioglioma. AB - A case of a rare intracerebral tumour, namely a ganglioglioma, is reported to illustrate the CT and MRI features. The finding of focal thinning of the inner skull vault in association with an adjacent intracerebral mass lesion can aid in the diagnosis of intracerebral ganglioglioma. PMID- 1520177 TI - Multifocal osteosarcoma with extensive pleural metastatic disease. AB - An eighteen year old female presented with multifocal synchronous osteosarcoma, with multiple skeletal foci of tumour in long bones, pelvis and spine. The radiographically dominant lesion was in the right ilium, and this was considered to be the primary site. There was an extensive osseous pleural plaque and there were also metastases to lungs, peritoneum, abdominal wall, adrenal gland and lymph nodes. A review of the literature reveals that multifocal osteosarcoma is an uncommon condition and is probably due to metastatic disease and not multiple primary lesions. Pleural metastatic disease in osteosarcoma has been seldom reported. PMID- 1520179 TI - Central neurocytoma. AB - One case of central neurocytoma is presented. A review of the literature suggests that the condition is more common than previously recognised. The pathological features are discussed and the role of surgery and radiotherapy in the management of the condition is discussed. PMID- 1520180 TI - Cerebro-costo-mandibular syndrome. AB - Cerebro-costo-mandibular syndrome (CCM) is a very rare entity with oro-facial features closely resembling Pierre-Robin anomaly (1,2). We describe a patient with typical features: severe micrognathia, glossoptosis, central cleft soft palate and multiple posterior rib-gap defects seen on chest radiograph. Respiratory distress which was evident soon after birth was relieved by an oro pharyngeal airway. He suffered from a cardiorespiratory arrest and succumbed, presumably secondary to aspiration of milk feeds, before a tracheostomy could be performed. PMID- 1520181 TI - A case of hepatic hydrothorax due to a large diaphragmatic defect. AB - Hepatic hydrothorax is an infrequent complication of cirrhosis. The source of pleural fluid has been the subject of considerable speculation. A case of hepatic hydrothorax is discussed which illustrates a large diaphragmatic defect as the cause of ascitic fluid passing into the pleural cavity. PMID- 1520182 TI - Lymphomatoid granulomatosis. AB - A case of lymphomatoid granulomatosis is presented demonstrating the most common chest radiograph findings as well as some infrequent but recognized associations. The clinical presentation and pathogenesis are discussed. The difficulty in radiological diagnosis is highlighted. PMID- 1520183 TI - Calcification of arterial arcade of colon in a patient with ischaemic colitis. PMID- 1520184 TI - High-grade chondrosarcoma of the sacrum--the crucial role of MR in surgical planning. PMID- 1520185 TI - Adrenal myelolipoma. AB - A case of adrenal myelolipoma demonstrated by ultrasound and computed tomography is presented with a discussion of the aetiology and review of literature. Ultrasound and CT proved to be invaluable in the pre-operative diagnosis of adrenal myelolipoma. PMID- 1520186 TI - Percutaneous removal of retained suture following antegrade ureteral stenting. PMID- 1520187 TI - Editor's case quiz (2). Urethral valves with massive urinoma. PMID- 1520188 TI - The use of human tissue type recombinant plasminogen activator in paraneoplastic arterial thrombosis--a non surgical option. PMID- 1520189 TI - Thrombolysis and the femorofemoral bypass graft: a new technique. AB - Two patients with acutely thrombosed femorofemoral bypass grafts are presented. Recombinant human tissue-type plasminogen activator (rt-PA) was used successfully in thrombolysis of the occluded grafts. Utilizing a new technique the grafts were punctured directly and bolus doses of rt-PA administered. PMID- 1520190 TI - Must macrosomic fetuses be delivered by a caesarean section? A review of outcome for 786 babies greater than or equal to 4,500 g. AB - Because difficult vaginal delivery is more frequent with macrosomic fetuses, some writers recommend routine Caesarean section for the delivery of fetuses greater than or equal to 4,500 g. The purpose of this study was to evaluate the appropriateness of this recommendation. A retrospective review was undertaken to determine how many fetuses born in our hospital weighing greater than or equal to 4,500 g died or were permanently damaged as a consequence of mechanical difficulties at delivery. During a 10-year period, 590 (75%) of 786 cephalic babies weighing greater than or equal to 4,500 g and alive at the start of labour were born vaginally. No baby died or was permanently damaged as a consequence of mechanical difficulties at delivery. Routine Caesarean section for macrosomic fetuses to prevent death or damage from difficult delivery is not warranted by our results. PMID- 1520191 TI - Why deliver in the supine position? AB - This study was conducted at the Lokmanya Tilak Municipal General Hospital, Bombay, India during the year 1990. The aim was to compare the routinely used supine position versus ambulation in the first stage and squatting position during the second stage of labour. Our study was comprised of 200 patients both primigravidas and multigravidas; 100 were kept in the supine position throughout labour and 100 were kept ambulatory in the first stage and adopted the squatting position during the second stage. The study showed a shortening of both stages of labour in the squatting group but the incidence of complications was less in the control group. It was concluded that without proper birthing chairs which can give excellent perineal support, the usual supine position is preferable in our setup. PMID- 1520192 TI - Antepartum cardiotocographic surveillance of patients with diminished fetal movements. AB - Over a 9-year period, 2,601 women had antenatal cardiotocography (CTG) performed after reporting diminished fetal movements. This series represented 5.6% of the total hospital population and 16.1% of those having antenatal CTG performed. The perinatal mortality rate (0.8%) and major fetal malformation rate (2.2%) were lower than in the hospital population (1.1% and 4.5% respectively). The incidence of abnormal CTG tracings was lower in the 1,390 women with diminished movements alone (6.4%) compared with the 1,211 who had additional antenatal complications (10.2%, p less than 0.001). Likewise the incidences of critical fetal reserve CTG and perinatal mortality were significantly lower in the group without additional complications (0.3% and 0.5%) compared with those with additional complications (1.7% and 1.2% respectively). The 24 patients with critical fetal reserve CTG were promptly delivered (19 by Caesarean section) with favourable results in 19, cerebral palsy in 1, and 4 perinatal deaths - 2 of these deaths resulted from intrauterine hypoxia (table 3, Cases 12 and 15). There were 17 perinatal deaths in cases where the CTG was satisfactory (13) or showed reduced reserve (4); 9 of these were unavoidable as a result of major malformations or other lethal conditions. The other 8 deaths resulted from hypoxia, including 4 in pregnancies at or beyond 37 weeks' gestation (table 3, Cases 6-9), illustrating that delivery is warranted in women with diminished fetal movements when conditions are favourable even when the CTG is satisfactory. Cardiotocography is useful in the management of patients with diminished fetal movements. PMID- 1520193 TI - Telephone fetal heart rate monitoring in South Australia. AB - A pilot trial was conducted to assess the technical feasibility of long range fetal heart monitoring by telephone in an Australian setting. The indications for such monitoring and patient ability and attitude towards self-monitoring was also assessed. One hundred and fifty seven tracings were received from 57 women using a simple doppler device to transmit fetal heart sounds to the central hospital fetal monitor. Thirty three of the patients were in country hospitals and 24 were at home. Gestation ranged from 26 to 42 weeks' gestation. Eighty six percent of the country hospital tracings and 94% of the home tracings were easily interpretable. The large majority of tracings were normal and appeared to encourage conservative management by the attendants. Two tracings were abnormal and these influenced early delivery in both cases. Nearly all women using the monitor at home found the procedure easy and reassuring. Tracings from country hospitals were initiated usually after an acute antenatal complication, whereas the indications for home-monitoring were prompted by longer-term, medium-risk factors. Home-monitoring may reduce the inconvenience and expense of inpatient or outpatient care and country hospitals without electronic fetal monitors may benefit from such a service. The selection of patients who might benefit from such technology remains controversial and warrants a prospective randomized controlled trial. PMID- 1520194 TI - Temperature drop in normal term newborn infants born at the University Hospital, Kuala Lumpur. AB - A prospective study of temperature drop in 141 normal term newborn infants delivered vaginally at the labour ward, University Hospital, Kuala Lumpur were studied. The effect of various manoeuvres on the temperature drop were also studied. They were randomized into 3 study groups, 63 cases where the babies were wiped with dry cloth alone, 37 cases where the babies were put into a plastic bag immediately after birth and lastly 41 cases where the babies were wiped with dry cloth and then inserted into a plastic bag. There was significant temperature drop in all the 3 groups maximum in the first 15 minutes and the fall continued for 1 hour after delivery (p less than 0.001). This shows that in an air conditioned labour ward in a tropical country the temperature fall in newborn infants can be significant. This study also showed that plastic is a poor insulator against significant temperature drop. PMID- 1520195 TI - Pregnancy outcome following preterm premature rupture of the membranes at less than 26 weeks' gestation. AB - The outcome of 71 singleton pregnancies where premature rupture of the membranes (PROM) occurred at gestations of less than 26 weeks was assessed retrospectively. The incidence of chorioamnionitis was 39.4% and the overall maternal morbidity rate was 53% but there were no long-term maternal sequelae. The latent period from PROM until delivery ranged from less than 12 hours to 77 days, with 41% of women delivering within 1 week. There was no increased risk of infection with increasing latent period. The perinatal mortality was 66.2% (26.7% stillbirths and 39.4% neonatal deaths). There was a 65% chance of a live baby if PROM occurred between 24-26 weeks but only 5 of 40 fetuses (12.5%) survived if PROM occurred before 24 weeks. The use of antibiotics, tocolytics and steroids in an uncontrolled manner is reported. Overall there is little serious risk to the mother if a conservative approach is adopted but only about one-third of such women will take home a live baby. PMID- 1520196 TI - The effect of smoking during pregnancy on the incidence of low birth weight among Chinese parturients. AB - The incidence and effect of smoking in Chinese parturients are not well known. In a retrospective case-controlled study of 213 patients who smoked during pregnancy, it was found that the incidence of low birth-weight was doubled. On average the babies were smaller by 200 g, shorter by 1 cm and the head circumference was smaller by 0.3 cm. These anthropometric deficits may have significant long-term effects. Although the incidence of smoking in Chinese parturients is low (2%), the rising trend in recent years should prompt all physicians to advise expectant mothers to avoid smoking before and during pregnancy. PMID- 1520197 TI - A case for revising the 'weight gain during pregnancy' guidelines for Australian women. AB - In 1989, an average weight gain during pregnancy of 14 kg was determined for a sample of 1,253 public patients at the Royal Women's Hospital, Brisbane. This greatly exceeded the weight gain of 10 to 12 kg which was recommended by the hospital and which is based on United States of America (US) data. The finding prompted a comparison of characteristics of Brisbane mothers (weight gain during pregnancy, age, prepregnant weight, height, birth-weight of infant, etc) with the characteristics of mothers in two large US studies. Significant differences were found to exist with Brisbane women being taller, heavier in body mass, more overweight and gaining less weight during pregnancy than the US women. Unexpectedly, the birth-weight of infants was neither more nor less than reported for the American studies. Further studies to gain more information about Australian women during their pregnancies should be undertaken. PMID- 1520198 TI - Answering MCQs: a study of confidence amongst medical students. AB - Medical students at the beginning of their obstetrics and gynaecology module were asked to complete a multiple choice question paper from an earlier module. Half the students were asked to answer only those questions where they were certain of the answers. The other half were asked to answer all questions. The mean mark in the second group was 86% higher than that in the first group. A computer programme was written where multiple choice questions were asked in a standard true/false format but instead of a don't know alternative the students were asked to rate their degree of certainty in having answered correctly on a scale of 0 to 100. Five students completed a total of 45 multiple choice question papers (each with 20, 5-part questions) both before and towards the end of their obstetrics and gynaecology module. The mean mark increased by 68.5% over the course of the module reflecting the students' increased knowledge. Their mean certainty level only increased by 50%, suggesting that the students underestimated their newly acquired knowledge. PMID- 1520199 TI - Invasive squamous cell carcinoma of the vulva: behaviour and results in the light of changing management regimens. A review of clinicohistological features predictive of regional lymph node involvement and local recurrence. AB - Ninety-nine patients with carcinoma of the vulva were referred to the Gynaecologic Oncology Unit, Royal Brisbane Hospital, over 10 years. Ninety of these patients had a squamous cell carcinoma (SCC). They were assessed by the 1969 FIGO clinical staging. Each stage was related to nodal involvement, size, depth, histological grade, lymphvascular space involvement, perineural permeation and multifocal disease site. The operability rate was 85%. Treatment was individualized in line with recent philosophies for more conservative surgery where appropriate. Mortality was 2.6%. Five-year survival of surgically treated patients was 60.3%; node negative patients 100%, and node positive patients 25.2%. After adjustment for stage and size, the only other independent statistically significant feature was perineural penetration. Local recurrence was more likely with increased stage and size, unclear margins and multifocal involvement. It is important to note that medically unfit patients who had vulvectomy alone and who later developed positive nodes had 100% mortality. This group of patients significantly decreases survival rates, confirming the importance of carrying out inguinofemoral lymphadenectomy at the time of initial surgery. Morbidity was decreased by conservative surgery. Lymphoedema remains the most common chronic complication. No significant difference was shown in local recurrence between different types of surgery, wide excision, hemivulvectomy, simple vulvectomy or radical vulvectomy (22%), confirming the safety of the more conservative approach of recent years. PMID- 1520200 TI - Free full-thickness vaginal epithelium graft in correction of recurrent genital prolapse. AB - Recurrence of a cystocele, rectocele or enterocele following a previous vaginal repair procedure can be an awkward problem to correct. This preliminary report suggests a simple yet very effective method of dealing with such defects. PMID- 1520201 TI - Reproductive performance following sleeve excision anastomosis operation for genital prolapse. AB - Genital prolapse is a disorder of pelvic support and is one of the most frequent disorders encountered in our gynaecological practice. Our social and cultural background predisposes to this condition to occur at an age which is reported to be earlier than any part of the world. Over a period of 4 years, 1986-1989, 17 cases were studied in whom the Sleeve Excision anastomosis operation was carried out, either at the Lokmanya Tilak Municipal General Hospital, Sion, Bombay, India or in some other hospital. All these patients were either admitted in active labour or as cases of abortions or were being treated for infertility. The incidence of full-term normal vaginal delivery in our study was 66.6% and the incidence of Caesarean section was 8.3%. There was 1 case of posterior wall rupture following previous sleeve excision anastomosis operation. The recurrence rate of prolapse in our series was only 7.7%. The Sleeve excision anastomosis operation has given excellent anatomical and obstetric results in our study and future multicentric trials will be necessary to study its effect on subsequent fertility to arrive at any final conclusion. PMID- 1520202 TI - The use of the semen analysis in predicting fertility outcome. AB - The study investigates the use of the various parameters of the semen analysis in predicting the fertility outcome in 82 infertile couples. The sperm density, % progressive motility, % normal morphology were divided into 'normal' and 'abnormal' based on the criteria proposed by WHO. The subsequent cumulative pregnancy rates were then calculated according to this criteria. A life-table method of analysis was used. All female related fertility factors were excluded. With the exception of a sperm density of less than 20 x 10(6) per ml the other parameters showed no significant correlation with the cumulative pregnancy rates at 12 months or 24 months respectively. We concluded that the semen analysis does not predict the probable outcome of the subsequent rates even when female fertility related factors were excluded apart from a sperm density less than 20 x 10(6) per ml. PMID- 1520203 TI - The use of clearplan home ovulation detection kits in unexplained and male factor infertility. AB - One hundred and five couples with unexplained infertility and 43 couples whose infertility was thought to be due to reduced sperm motility were recruited. The median duration of infertility was 36 months (range 12-168). Couples were randomly allocated to either using Clearplan home ovulation detection kits for 3 cycles or were advised about the optimal time during their menstrual cycle to achieve a pregnancy. The clinical details of the 2 groups were similar. In couples with unexplained infertility over the study period 10 (20.4%) in the Clearplan group and 9 (16%) in the control group conceived with 58% of pregnancies occurring in the first cycle. In couples with reduced sperm motility, the results were disappointing with only 2 (8%) pregnancies in the Clearplan group and 2 (11.1%) in the controls. Assisted reproduction technology may not be justified as the first line of management in patients with unexplained infertility. PMID- 1520204 TI - Endometriosis and race. AB - The pelvic findings of 202 infertile women undergoing diagnostic laparoscopy in Kuala Lumpur, Malaysia were compared to that of 464 infertile women undergoing diagnostic laparoscopy in Aberdeen, United Kingdom. Endometriosis was significantly more common in the women from Kuala Lumpur (51% against 22%, p less than 0.001). There was however no significant difference seen in the severity of the disease (AFS Classification, 1985). These findings confirm our clinical impression that endometriosis is more common in Asian women when compared to Caucasian women. PMID- 1520205 TI - A comparison of tiaprofenic acid, mefenamic acid and placebo in the treatment of dysmenorrhoea in general practice. AB - The efficiency and side-effects of tiaprofenic acid, mefenamic acid and placebo were compared in the treatment of primary dysmenorrhoea. The trial was a double blind prospective randomized 3-way crossover study during 6 successive menstrual cycles following a 2-cycle run-in period and involved 50 women with primary dysmenorrhoea selected from 96 volunteers between 16 and 35 years of age. Overall pain was significantly less (p less than 0.05) on treatment with tiaprofenic acid than on treatment with mefanemic acid, placebo, or the women's usual treatments. Both active treatments were well tolerated but more side-effects were reported during treatment with mefenamic acid. PMID- 1520206 TI - Undiagnosed maternal Fallot tetralogy presenting in pregnancy. PMID- 1520207 TI - A case of intrauterine fetal death associated with maternal Campylobacter coli bacteraemia. AB - Campylobacter species are known to cause infectious abortion in domestic animals. In humans, Campylobacter are an important cause of enteritis, an occasional cause of systemic infection and have had a rare association with abortion and perinatal infection. A case history of spontaneous abortion, at 26 weeks' duration, associated with maternal bacteraemia, due to Campylobacter coli is presented. Transmission, pathogenesis, treatment, and the need for further investigation are discussed. PMID- 1520208 TI - The diagnosis of marginal placental abruption in placenta praevia using transvaginal sonography. PMID- 1520209 TI - An unusual case of retrograde ejaculation. AB - Despite normal seminal analyses obtained for assay by masturbation, persistent negative postcoital tests led to the testing of postejaculatory urine following normal intercourse. This disclosed an unusual problem of retrograde ejaculation occurring only during intercourse. The mechanism for this selective form of retrograde ejaculation is unknown. PMID- 1520210 TI - Caesarean section rates, Australia 1986: variations at state and small area level. PMID- 1520211 TI - Alcoholic liver disease with subsequent hyperoestrogenism. PMID- 1520212 TI - HIV infection in pregnancy; the position in the United Kingdom and Europe. PMID- 1520213 TI - Early growth retardation in the first trimester: is it characteristic of the chromosomally abnormal fetus? AB - There have been recent reports on a small number of cases which suggest that the detection of early growth retardation might allow recognition of the chromosomally abnormal fetus in the first trimester of pregnancy. To amplify these observations, the crown-rump length (CRL) measurements between the 64th and 86th day of menstrual age were determined in (a) 500 control high risk patients in whom a normal karyotype was subsequently demonstrated by chorionic villus sampling (CVS) and (b) 25 chromosomally abnormal fetuses. The data indicate that early growth retardation, as expressed by a small CRL measurement, is not a special characteristic of the chromosomally abnormal fetus in the first trimester of pregnancy. The CRL measurement is therefore not a useful marker or screening test at that time, except perhaps for triploidy. The well documented growth retardation with trisomy 21 and trisomy 18 which has been observed in the second trimester does not begin until after the 12th week of menstrual age. PMID- 1520214 TI - Amniocentesis and its complications. AB - This study was conducted in order to evaluate whether the performance of an experienced operator had any significant influence in reducing the incidence of complications in amniocentesis; 1,459 women had amniocentesis performed under ultrasound guidance; 1,324 were performed by experienced operators and 135 cases by less experienced operators. Complications like fetal loss, blood-stained amniotic fluid, culture failure, multiple needle puncture, leaking liquor, fetal trauma and error in results were compared in the 2 groups. This study demonstrated that amniocentesis performed by an experienced operator decreased the various complications associated with amniocentesis. PMID- 1520215 TI - Hemodynamic responses to seated and supine lower body negative pressure: comparison with +Gz acceleration. AB - Hemodynamic changes between upright and supine lower body negative pressure (LBNP) to levels of -70 mm Hg were compared in 8 subjects (5 males, 3 females) and correlated with their findings during simulated Shuttle reentry acceleration with a slow onset rate of 0.002 G/s (1,020 s to peak +2 Gz) and during gradual onset exposures (0.03 G/s) to +3 Gz and +4 Gz. Six of the 8 subjects were able to tolerate 2 min at peak +2 Gz, 2-5 min at +3 Gz, and 1-2 min at +4 Gz. Heart rate (HR) at any given level of upright LBNP regularly exceeded supine levels. HR change at -50 mm Hg in upright subjects (+47.7 bpm from 74.1 +/- 1.9 (M +/- S.E.) bpm, control) was 2.6 times greater than in supine subjects (+18.3 bpm from 64.8 +/- 2.8 bpm, control). HR values at -40 mm Hg supine (73.7 +/- 2.6) matched seated upright pre-LBNP control levels (74.1 +/- 1.9 bpm), while values at -70 mm Hg supine (102.5 +/- 4.4 bpm) were not significantly different from those at -40 mm Hg upright (103.1 +/- 4.0 bpm). Peak HR during +3 Gz (145.8 +/- 7.7 bpm) and +4 Gz (152.3 +/- 6.5 bpm) significantly exceeded recorded supine and upright LBNP levels, whereas values at +2 Gz (104.8 +/- 5.5 bpm) closely matched those at -40 mm Hg upright (103.1 +/- 4.0 bpm) and -70 mm Hg supine (102.5 +/- 4.4 bpm). Supine LBNP HR changes in this relatively small group of subjects closely matched those previously reported in the literature.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1520216 TI - Physiologic validation of a short-arm centrifuge for space application. AB - A short-arm centrifuge (SAC) of 5-6 ft (1.5-1.8 m) radius may be useful in space to measure tolerances to acceleration (G) and to stimulate the cardiovascular system, thereby reducing cardiovascular decompensation that occurs in weightlessness. Relaxed rapid (1G/s onset rate, ROR) and gradual (0.1 G/s onset rate, GOR) G tolerances were measured on seven men using a 5-ft (1.5 m) radius centrifuge and compared with their G tolerances obtained on the 20-ft (6.1 m) radius human-use centrifuge at the Armstrong Laboratory, Brooks AFB, TX. Since the subjects were required to flex their legs to assume a squatting position on the SAC, a similar position was used on the 20 ft (6.1 m) centrifuge called feet up (FU), and compared with normal-seated +Gz tolerances (controls). The subjects tolerated the SAC exposures without any problems. ROR and GOR tolerances were as follows: control, 3.6 G and 4.2 G; FU, 4.5 G and 5.6 G; and SAC, 4.6 G and 6.4 G. We concluded that a 5-ft radius centrifuge can be used to measure G tolerances. The increases in the SAC GOR tolerances over ROR tolerances indicate that the baroreceptors were stimulated by the G, and the SAC exposure would be useful in preventing cardiovascular decompensation in microgravity. PMID- 1520217 TI - A biomechanical perspective on exercise countermeasures for long term spaceflight. AB - Many systems of the body undergo adaptation on exposure to hypogravity, with the lower extremity skeleton experiencing considerable mineral loss during relatively short periods of hypogravic exposure. To date, a variety of countermeasures have had limited success in preventing demineralization, though it is now accepted that mechanical deformation is critical for bone homeostasis on Earth. In the present study, three exercises under active consideration for use in the Space Station were compared in 1 G in terms of the peak loads and rates of change of load elicited under the feet. Peak loading rates were in the ratio of 34.7:1.9:1 for running, rowing, and cycling, respectively. With regard to peak foot loads, the corresponding values were in the ratio of 5.3:1:1.2. These results suggest that exercise during spaceflight must be considered from both biomechanical and physiological perspectives if optimal response is to be obtained. PMID- 1520218 TI - Motion sickness and equilibrium ataxia. AB - In order to know the relationship between motion sickness and equilibrium ataxia, we performed Graybiel's ataxia test battery on 10 normal subjects: 1) before donning goggles which reversed the optical image horizontally and vertically; 2) while wearing the goggles and walking; and 3) after walking as long as possible up to 90 min. Horizontal reversal of vision resulted in a statistically significant decrease in the score for all the closed-eyes tests and one open-eyes test performed during walking and after walking, respectively. In contrast, walking while wearing vertical reversing goggles produced a significant but very small change for one of the closed-eyes tests alone. The present study indicates that failure to detect spatial orientation, which evokes autonomic nervous symptoms as an alarm sign, produces equilibrium ataxia by impairing the top-down regulation of body balance, and that vertically reversed vision does not impair spatial orientation needed to maintain upright posture or to execute locomotion. PMID- 1520219 TI - A comparison of the nauseogenic potential of low-frequency vertical versus horizontal linear oscillation. AB - The aim of this study was to compare the nauseogenic potential of low-frequency linear motion in the Earth-vertical versus the Earth-horizontal plane, delivered through the same Z-axis of the head and body. Twelve subjects were challenged with linear motion (0.3 Hz, 1.8 ms-2 rms) through the same head and body Z-axis in the Earth-vertical (sitting upright) versus horizontal (lying on the back), while either performing a continuous visual search task or with their eyes closed. Each subject completed the four conditions on a Latin square design with sessions spaced 1 week apart at the same time of day. Vertical motion was clearly more provocative than horizontal motion, and nauseogenicity of motion was exacerbated by a visual search task. Motion sickness impaired performance of the search task. Motion Sickness Susceptibility Questionnaire (MSSQ) scores correlated with individual susceptibility to the motion challenge. Mean sickness ratings for vertical motion showed some correspondence with those predicted by mathematical models of motion sickness dose response relationships. PMID- 1520221 TI - Effect of simulated air combat maneuvering on muscle glycogen and lactate. AB - Muscle glycogen and muscle and blood lactate were evaluated before and after a +4.0/7.0 Gz simulated air combat maneuvering (SACM) protocol in the human centrifuge. The subjects were eight healthy males, ages 25-43 years. Muscle glycogen and lactate were determined from biopsies of m. vastus lateralis in six subjects and whole blood lactate was analyzed in finger-tip blood samples from eight subjects. G-tolerance time was 256 +/- 33 s (Mean +/- S.E.M.). The decrease in glycogen concentration averaged 81 +/- 36 mmol.kg-1 dry wt (p = 0.07). The rate of glycogen utilization was low, averaging 0.4 +/- 0.1 mmol.kg-1.s-1. Muscle lactate increased significantly from 28 +/- 2 mmol.kg-1 dry wt pre-SACM to 51 +/- 4 mmol.kg-1 post-SACM. Post-SACM blood lactate was 4.2 +/- 0.3 mmol.L-1. Neither final blood nor muscle lactate values nor the difference between pre- and post SACM muscle lactate concentrations were related to G-tolerance time. It was concluded that glycogen availability in m. vastus lateralis is not a limiting factor during exposure to headward acceleration of this type and duration. The lactate values, while high, cannot fully explain the muscular fatigue occurring during centrifuge exposures of the type used here. Therefore, the suggestion by others that anaerobic energy metabolism in skeletal muscles is the crucial factor limiting the ability to resist fatigue during exposure SACM is not supported and is likely an oversimplification of a much more complex problem. PMID- 1520220 TI - The effects of perceived motion on sound-source lateralization. AB - Lateralization of dichotic click pairs differing in time of onset was studied under conditions of angular acceleration, optokinetic stimulation, and gaze fixation. Data obtained from 20 subjects with normal hearing indicate poorer left right judgment performance for small time differences, as well as shifts in subjective simultaneity, for all experimental conditions relative to control conditions. In addition, response times increased for the experimental conditions. The results suggest that real or apparent motion may affect an individual's ability to process one of the major cues for sound-source localization--binaural time difference--under conditions similar to those encountered in vehicular motion. PMID- 1520222 TI - The effects of hypoxia on components of the human event-related potential and relationship to reaction time. AB - This experiment investigated the relationship between the increase in reaction time (RT) caused by hypoxia and the P300, N200, P200 and N100 components of the event-related brain potential. Eight subjects breathed air or a low oxygen mixture (65% arterial oxyhemoglobin saturation) and RT was collected to visually presented stimuli at two levels of stimulus intensity while ERPs were recorded. An hypoxia x stimulus intensity interaction was found for RT, P300 latency and N200 latency. P200 latency and N100 latency were unaffected by hypoxia. These results were interpreted in terms of Additive Factors Method logic to indicate that the preprocessing stage of stimulus evaluation is slowed by hypoxia and that both P300 and N200 index this slowing. PMID- 1520223 TI - A review of microgravity surgical investigations. AB - The likelihood of performing a surgical procedure in space will increase as the Soviet Mir space station is expanded and the Space Station Freedom becomes operational. A review of previous research and hardware development, performed mostly in parabolic flight both in the Soviet Union and the U.S., reveals an interest in surgical chambers to prevent cabin atmosphere contamination. Surgical techniques appear to be no more difficult than in a 1-G environment if a restraint system is used. Minimizing the chances of wound infection from the high particle count spacecraft atmosphere is an additional concern. Additional research is necessary to delineate the clinical significance of these problems and to further develop surgical techniques in microgravity. PMID- 1520224 TI - Compulsive personality traits affecting aeronautical adaptability in a naval aviator: a case report. AB - This is a case report of a male naval aviator who demonstrated compulsive personality traits which adversely affected the performance of his duties as a pilot trainee, and later, as a naval flight officer. The Diagnostic and Statistical Manual of the American Psychiatric Association (DSM-III-R) uses the term obsessive-compulsive to describe two conditions. A review of terminology is undertaken to present the reader with the distinguishing features of the personality disorder versus the anxiety disorder. The anxiety disorder, obsessive compulsive disorder, is incompatible with safe performance of aviation duties. Obsessive-compulsive personality, on the other hand, describes a point on a continuum where useful, adaptive compulsive traits may become abnormally exaggerated and maladaptive, thus interfering with the aviator's normal routine, occupational functioning, relationships with others, and aviation safety. PMID- 1520225 TI - A survey of blood lipid levels of airline pilot applicants. AB - Cardiovascular disease represents the single largest cause of premature career termination for airline pilots--an entity approximately equal to all other medical causes combined. It is obviously essential to assess risk factors for the development of cardiovascular disease among airline pilots. For that reason, we obtained lipid levels for 14,448 pilot applicants examined during the period from March 1984 through December 1988. Blood lipid levels are well-documented predictors for future cardiovascular diseases. We determined total cholesterol values, high density lipoprotein (HDL) levels, and the cholesterol/HDL ratio for these lipids for our applicant population. We present these data in tabular and graphic form. They suggest a cessation of any increase in blood lipid levels during the fifth decade of life. While the cause is not obvious, there are a number of factors which may play a role in this finding. PMID- 1520226 TI - Development of a new device to measure local heat exchange by evaporation and convection. AB - According to the principles of heat and mass transfer, the rate of local heat exchange by convection (C) and local heat loss by evaporation (E) can be estimated if temperature and vapor concentration profiles in the boundary layer are measured. In addition, temperature (Ts) and vapor concentration (rho s) at the surface may be predicted from the measured profiles. On this basis, a new device was developed to measure parabolic profiles by incorporating three relative humidity sensors coupled with thermistors into its probe. It has been evaluated from various tests including human experiments. The results showed that the device, with humidity sensors arranged perpendicular to the surface, could estimate C, E, Ts, and rho s in closer agreement with direct measurements when compared with the conventional gradient method. This confirmed that our method had clear advantages over the conventional gradient method under laminar air flow conditions. PMID- 1520227 TI - Malcolm C. Grow and the Alaskan flight. PMID- 1520228 TI - Aeromedically-trained psychologist in the flight surgeon's office. PMID- 1520229 TI - The abstinence violation effect in sex offenders: a reformulation. AB - It is argued that the central issue in the treatment of sexually aggressive behavior is the tendency to relapse shown by offenders. A model of the relapse process is presented along with what is described as its central feature, the abstinence violation effect (AVE). This construct is critically examined and its shortcomings identified. A brief description of Weiner's attributional theory is provided and this is used to reformulate the AVE. The advantages of the reformulated AVE are described, as are the clinical implications. Suggestions are then made for future research. PMID- 1520230 TI - Severity of unipolar depression and choice of treatment. AB - The National Institute of Mental Health (NIMH) Treatment of Depression Collaborative Research Program (Elkin et al., Archives of General Psychiatry, 46, 971-982; 1989) reported treatment-by-severity interactions favouring pharmacotherapy for more depressed outpatients, on a minority of relevant comparisons. The present study reports secondary analyses from a similar, preexisting data set in which treatment-by-severity interactions are systematically investigated with depressed outpatients treated either with nondirective psychotherapy, behaviour therapy, pharmacotherapy, or relaxation/placebo. Despite multiple severity measures and variable severity cut scores, no treatment was differentially effective in improving more severely depressed patients. Also, there was little difference across symptom severity levels in the proportions of recovered patients between treatment groups. Finally, dynamic cluster analysis demonstrated that the proportion of pharmacotherapy nonresponders (20%) did not differ from the proportion of nonresponders in behaviour therapy or placebo groups. It is concluded that this failure to replicate the NIMH trial findings can not be attributed to treatment differences, populations or statistical power. The suggestion that pharmacotherapy be the treatment of choice for more severely depressed outpatients appears to be unjustified on the basis of available evidence. PMID- 1520231 TI - The hyperventilation provocation test in panic disorder. AB - Forty-eight patients with DSM-III-R Panic Disorder underwent a hyperventilation provocation Test (HVPT). Twenty-four patients rated the symptoms induced during the HVPT as similar to those occurring during panic attacks in daily life. Contrary to the classical hyperventilation model of panic, no differences were found in respiratory physiology between recognizers and non-recognizers before and during voluntary hyperventilation. Moreover, recognizers and non-recognizers reported comparable levels of panic and hyperventilation symptoms and state anxiety during panic attacks in daily life. Ten of the recognizers also had a panic attack during the HVPT, independent of any differential CO2 alterations. Compared to non-panickers, panickers obtained higher scores for agoraphobia and depression. On the basis of these results, it is concluded that recognizers or panickers do not show a tendency towards hyperventilation, but that reports of severe panic and hyperventilation symptoms are more closely related to the level of anxiety. These results are more consistent with the cognitive model of panic, which emphasizes the patient's tendency to interpret somatic symptoms catastrophically. PMID- 1520232 TI - Cognitions and courage in the avoidance behavior of acrophobics. AB - Fifty subjects (29 fearless and 21 fearful) were tested in a potentially acrophobia-inducing situation, and their avoidance behavior and self-reported fear were noted. Subjects also completed various scales intended to measure their fearfulness and thoughts in hypothetical height-phobic, social-phobic and nonphobic situations. Interviews conducted immediately after the behavioral test, evaluated their thinking, fearfulness and tactics designed to deal with any fear they experienced. Analyses indicated that catastrophic thinking is more evident than irrational thinking in height situations and that such thinking was the best predictor of behavior among the measures used. The results are discussed in terms of their relevance for cognitive views of acrophobia and in terms of their relevance for treatment. PMID- 1520233 TI - Pain-elicited responses and their role in predicting future pain duration and severity. AB - The first objective of this study was to carry out a prospective investigation of the behavioral and affective responses to headache pain over a 72 hr period. A sample of 74 headache sufferers provided self-reported ratings of affective and behavioral responses as measured by a composite of standardized questionnaires. Highly significant and clinically meaningful levels of both types of responses were found on the headache day. Interestingly, significant levels of behavioral and affective disturbances were also reported 24 hr after pain termination, indicating that responses to pain actually outlasted pain perception by at least 1 day. The second goal of this study was to investigate whether affective or behavioral responses were predictors of future pain intensity, duration or severity. A smaller sample of 25 subjects provided ratings on two sequential headaches. A series of time-lag analyses indicated that, unlike behavioral responses, strong affective responses during a given episode were associated with subsequently longer and more severe headaches. These results suggest that affective pain-elicited responses may be a risk factor for suffering a worse headache during the episode that follows. PMID- 1520234 TI - Anxiety and the selective processing of emotional information: mediating roles of awareness, trait and state variables, and personal relevance of stimulus materials. AB - Previous research has established that anxiety patients demonstrate a cognitive bias that selectively favours the processing of threat related information. The current experiment employs a variant of a well established colour naming paradigm to address three issues concerning the nature of this anxiety linked pattern of selective processing. First, by considering non-clinical subjects and employing an experimental design capable of dissociating the influence of state and trait anxiety, the current study addresses the hypothesis that state anxiety elevations will elicit differential patterns of selectivity in high and low trait anxious subjects. Second, by presenting stimulus materials within or outside awareness, the study addresses the hypothesis that these processing biases occur automatically, without requiring the use of consciously mediated strategies. Third, by including both emotionally valenced stimulus materials which are related to, and which are unrelated to, the particular source of stress experienced by the subjects, the experiment addresses the hypothesis that such anxiety linked processing biases will be restricted to materials falling within the domain of current personal concern. The results of the present study clearly demonstrate that these three issues are not independent. Fundamentally different patterns of anxiety linked selective processing were observed when stimuli were presented outside awareness, permitting only automatic cognitive processing, and when stimuli were presented within awareness, permitting the use of consciously mediated strategies. The relative roles played by state and trait variables, and the degree to which these effects were influenced by the personal relevance of the stimulus materials, differed in each case. The implications of these findings for future research in this field are discussed. PMID- 1520235 TI - Physical symptoms and illness attributions in agoraphobia and panic. AB - The cognitive model of panic disorder proposes that panic patients interpret physical symptoms in a catastrophic way, thus precipitating panic attacks. This study describes the development of a questionnaire measure designed to assess beliefs about the health implications of various symptoms. Two groups, agoraphobics and normals, were compared on a variety of measures. Agoraphobics showed much higher panic frequency, fear of anxiety, and prevalence of frightening cognitions when anxious, but did not score higher than normals when assessing seriousness of symptoms. The implications of these results are considered. PMID- 1520236 TI - Thoughts about eating, weight and shape in anorexia nervosa and bulimia nervosa. AB - Concurrent verbalisation and a self-report questionnaire were used to investigate self-statements in patients with anorexia nervosa, patients with bulimia nervosa, two groups of dieters and non-dieting controls. Thoughts were collected while subjects performed three behavioural tasks, looking at themselves in a full length mirror, weighing themselves and eating a chocolate covered mint. Both groups of patients had more negative thoughts related to eating, weight and shape than those in the three control groups. In addition, patients with anorexia nervosa showed a greater concern with eating while patients with bulimia nervosa showed a greater concern with weight and appearance. Differences were found between the patients and non-dieting controls using both methods but the self report questionnaire was less sensitive than concurrent verbalisation to differences between the patients and dieters. Implications of the findings for cognitive-behavioural treatments of the two disorders are discussed. PMID- 1520237 TI - Pain and fear: a bioinformational perspective on responsivity to imagery. AB - Cognitive processing of pain and fear information was examined using a methodology based on the bioinformational theory of emotion. Undergraduate volunteers (n = 48) participated in an imagery assessment procedure involving audio presentation of pain, fear, or pain plus fear experimental scripts. Action and neutral scripts were presented as control stimuli. Heart rate and self reported affective judgements were assessed. Results indicated that pain scripts were rated more negatively, and were associated with feelings of less dominance than the other experimental scripts. Fear scripts elicited greater heart rate acceleration than either pain or pain plus fear scripts. The direction of physiological and verbal response to pain scripts and fear scripts, however, was very similar, differing only in amplitude; greater heart rate response and more negative ratings were manifested relative to action or neutral scripts. PMID- 1520238 TI - Self report assessment of anxiety: a cross validation of the Lehrer Woolfolk Anxiety Symptom Questionnaire in three populations. AB - This study was meant to investigate the psychometric properties and clinical utility of the Lehrer Woolfolk Anxiety Symptom Questionnaire (LWASQ), an instrument for assessment of somatic, behavioral and cognitive aspects of anxiety. Confirmatory factor analysis on data from social phobics (n = 108), normal adults (n = 103) and normal adolescents (n = 650) showed that the three original factors were strongly replicated in each sample. The three subscales appeared to have high internal consistency, while data on convergent and divergent validity were satisfactory. In addition, the subscales did very well in discriminating between phobic patients and normals, and were able to detect treatment effects. In the discussion the instrument is compared with other self report measures of anxiety dimensions, like the Cognitive Somatic Anxiety Questionnaire (CSAQ) and the Worry-Emotionality Scale (WES). It is suggested that similar questionnaires, adjusted to the separate anxiety disorders, should be developed. PMID- 1520239 TI - Juvenile sex offenders: similar to, or different from, other incarcerated delinquent offenders? AB - The purpose of the present study was to compare incarcerated juvenile sex offenders to incarcerated youth who committed confrontational but nonsex offenses, and to those youth who committed only nonconfrontational, nonsex offenses. Furthermore, comparisons were made between two subtypes of sex offenders: those youth convicted for rape or sodomy vs those convicted for child molestation. Eighty-three male juvenile delinquents served as participants. Teachers within the correctional facility completed an instrument which allowed the examination of the two areas of interest: externalizing problems and internalizing problems. The results indicated that sex offenders generally, and particularly those who had committed only sex offenses, were perceived as having fewer externalizing and internalizing problems. No differences emerged between the two subtypes of sex offenders. Implications, as well as limitations, of the findings are discussed. PMID- 1520240 TI - Suicide attempts among juvenile delinquents; the contribution of mental health factors. AB - This study examined which, if any, of four variables (depression, hopelessness, conduct problems, substance abuse) differentiated suicide attemptors from nonattemptors among incarcerated juvenile delinquents. Fifty-one male youth served as subjects. The predictor variables were collected by either a standardized interview or an orally administered questionnaire. Youth self-report data regarding suicide attempts were collected. The results indicated that depression served as a predictor of suicide attempts but only in white, not black, youth. Suicide attempts also were reported three times more often in white than black participants. Implication, as well as limitations, of the findings are discussed. PMID- 1520241 TI - Pathways to spider phobia. AB - Using a revised version of the Phobic Origin Questionnaire (POQ; Ost, L. G. & Hugdahl, K. Behaviour Research and Therapy, 19, 439-477; 1981), the present study examined whether conditioning experiences, modeling experiences, and/or informational learning experiences were more often reported by spider phobics (n = 41) than by non-fearful controls (n = 30). The two groups did not differ with regard to the overall frequency of conditioning or modeling events. Remarkably, the frequency of informational learning was higher among non-fearful Ss than among phobics. Although the limitations inherent to the retrospective nature of the present study should be borne in mind, the data suggest that, at least in spider phobics, conditioning events, modeling experiences, and/or informational learning do not necessarily give rise to phobic fears. PMID- 1520242 TI - Do drop-outs differ from successfully treated obsessive-compulsives? AB - The most common reasons given by patients for dropping out of treatment are: environmental constraints, dissatisfaction with services and that they no longer need help. In this study two groups of patients suffering from obsessive compulsive disorders are compared. The drop-outs' reasons for terminating treatment are compared with the comments of patients who completed the therapy successfully. Drop-outs differ from successfully treated OCD's in five respects: they appear to be less obsessive-compulsive; they have more discongruent treatment expectations; they are more critical of the therapist; they experience less anxiety in carrying out homework assignments; they less frequently come under pressure from people close to them. PMID- 1520243 TI - One-trial backward excitatory fear conditioning transfers across contexts. AB - One path to human phobia may be one-trial backward fear conditioning. Human phobias transfer readily across contexts. However, animal studies of one-trial backward fear conditioning have yet to demonstrate such transfer. The present study sought to do so. It used a lick-suppression procedure with 84 naive male albino rats. Two conditioning contexts, designated O and V, were crossed factorially with two test contexts, O and V. Within each cell of the factorial design, rats received in the conditioning context either a single 12 sec tone backward paired with a single 4 sec 1 mA shock or the same tone explicitly unpaired with shock. Fear of context and fear of tone were subsequently assessed in terms of the suppression of licking that they evoked. Test results suggested that (1) the rats discriminated between contexts O and V, and (2) despite such discrimination, one-trial backward fear conditioning transferred across the two contexts. The results enhance the plausibility of one-trial backward fear conditioning as a source of human phobia. PMID- 1520244 TI - State and trait differences in depressive self-perceptions. AB - A number of investigators have interpreted a tendency for depressed people to recall more negative than positive self-referent adjectives as evidence for a depressive self-schema made up of predominantly negative characterological information. We sought to confirm this account by eliciting the subjective self perceptions of the depressed. Depressed patients and controls were required to rate whether or not a series of positive and negative adjectives applied to them during the previous week, at any time, and generally. The depressed distinguished clearly between these questions and, although describing themselves currently in largely negative terms, described their general state as equally composed of positive and negative elements. PMID- 1520245 TI - The effects of masturbatory reconditioning with nonfamilial child molesters. AB - Abel and Annon's (Reducing deviant sexual arousal through satisfaction, Denver, Colo., 1982) suggested combination of 'directed masturbation' and 'satiation' to alter deviant sexual preferences, was applied to 10 nonfamilial child molesters. Post-treatment assessments revealed significant reductions in deviant arousal as was expected, but unfortunately there were also reductions in appropriate arousal although these changes did not achieve statistical significance. The results are discussed in terms of their meaning but it is concluded that empirical support for these clinically popular procedures remains weak. PMID- 1520247 TI - Three-dimensional analysis of regional mechanical function, blood flow and electrophysiological parameters during early myocardial ischemia in dogs. AB - Ventricular arrhythmias are primarily responsible for sudden cardiac death early after the onset of acute myocardial ischemia. We designed an experimental model to simultaneously characterize regional myocardial function, myocardial blood flow, and electrophysiological parameters, and to determine predisposing factors for the development of early ventricular arrhythmias (EVA). The left circumflex coronary artery was occluded in six anesthetized (n = 2 piritramide/N2O, n = 4 chloralose/urethane) mongrel dogs. Systolic wall thickening (%WT) in a control zone and in the central ischemic zone was measured with sonomicrometry and regional myocardial blood flow (RMBF) with colored microspheres. Excitability and relative refractory period at the stimulus electrode and conduction times to all other electrodes were determined with a three-dimensional transmural multi(16) electrode assay using a computer algorithm. In three of six dogs spontaneous EVA occurred 4 to 6 min after coronary occlusion, degenerating to ventricular fibrillation in two of these dogs. The three dogs developing EVA were not distinguished from those not developing EVA, neither by the kind of anesthesia nor by ischemic % WT (-6.6 +/- 3.8 [SD] vs -7.8 +/- 1.6, ns). Also, dogs with and without EVA did not differ significantly in excitability and relative refractory period. In contrast, dogs with EVA were characterized by a greater mass of severely ischemic myocardium, i.e., exhibiting a RMBF reduction to less than 0.1 ml/(min.g) (18 +/- 3 g vs 7 +/- 4 g, p less than 0.05), and by an increase in subendocardial conduction times of greater than 100% above the respective pre ischemic values (120 +/- 18% vs 66 +/- 9%, p less than 0.05). Dogs with and without EVA were not as clearly distinguished by the increases in subepicardial (81 +/- 22% vs 46 +/- 15%, ns) and transmural (98 +/- 31% vs 67 +/- 14%, ns) conduction times. The development of EVA is associated with a greater mass of severely ischemic myocardium and a greater increase in subendocardial conduction times. PMID- 1520246 TI - Frequency-dependent action of antiarrhythmic drugs: the useful concept of periodical ligand binding. AB - The action of most antiarrhythmic drugs which block cardiac ionic channels depends on heart rate, which is established as use- or frequency-dependence. This property is consistent with periodical drug (ligand) binding to channel binding sites which are transiently available during the excitation sequence of cardiac tissue. Antiarrhythmic drugs differ with respect to their binding and unbinding kinetics, i.e., with respect to their blocking and unblocking kinetics. This gives rise to different block-frequency relations and onset-kinetics of frequency dependent ion channel blockade. Antiarrhythmic drugs have never been systematically compared with regard to their block-frequency relations. However, both the onset-kinetics as well as the block-frequency relation are essential in characterizing the frequency-dependent drug action, since both may be predictors of the anti- and pro-arrhythmic potential of antiarrhythmic drugs. PMID- 1520248 TI - Allopurinol-enhanced myocardial protection does not involve xanthine oxidase inhibition or purine salvage. AB - Isolated working rat hearts were subjected to aerobic perfusion (25 min), cardioplegic infusion (3 min), global ischemia (30 min at 37 degrees C) and reperfusion (35 min). Measurements of myocardial xanthine oxidase and dehydrogenase activity, together with various adenine nucleotides and metabolites, were made at defined stages of the protocol (n = 6/group). Allopurinol pretreatment (20 mg/kg body wt/day for 3 days) improved the postischemic recovery of cardiac function; thus, aortic flow (a representative index) recovered to 68.8 +/- 4.2% compared with 53.2 +/- 2.3% in untreated controls (p less than 0.05). In fresh tissue, allopurinol pretreatment inhibited xanthine dehydrogenase activity by 73.1% (from 11.9 +/- 0.5 to 3.2 +/- 0.8 mIU/g wet wt: p less than 0.05) and xanthine oxidase activity by 95.2% (from 8.3 +/- 1.2 to 0.4 +/- 0.2 mIU/g wet wt: p less than 0.05); however, this inhibition was not maintained during perfusion. During reperfusion, myocardial xanthine dehydrogenase and oxidase activity was reduced by 40-60% (p less than 0.05) in both allopurinol pretreated and control hearts. Tissue content of creatine phosphate, adenosine triphosphate and catabolites, NAD and inorganic phosphate were not different in allopurinol pretreated or control hearts during either ischemia or reperfusion. This study does not support the concept that allopurinol protects the rat heart during ischemia and reperfusion by inhibition of xanthine oxidase activity or by conservation of purines. It appears that allopurinol achieves its protective effects by some, as yet undefined, mechanism. PMID- 1520249 TI - Role of cellular defense against hydrogen peroxide-induced inhibition of myocyte respiration. AB - Hydrogen peroxide (H2O2) serves as a precursor for highly reactive oxygen intermediates. However, the respiratory function of myocytes is relatively resistant to exogenously administered H2O2. In this study, we examined whether or not the reduction of cellular defense increases the toxicity of H2O2. Rat heart myocytes were isolated by collagenase digestion. Respiratory rates of myocytes, suspended in a medium containing sucrose, 3-N-morpholino-propanesulfonic acid, EGTA and bovine serum albumin, were determined polarographically in the presence of pyruvate and malate with or without 2,4-dinitrophenol (DNP). Mitochondrial membrane potentials were measured by using [3H]triphenylmethylphosphonium+. Cellular defense was attenuated by i) inhibiting the catalase activity by 3-amino 1,2,4-triazole (AT), ii) reducing the glutathione concentration by diethyl maleate (DEM) or ethacrinic acid (EA), and iii) permeabilizing the sarcolemmal membrane by saponin. The dose-response relationship between H2O2 (0.1-5 mM) and mitochondrial membrane potential was not greatly affected by these experimental conditions. Myocyte respiration was inhibited by 5 mM H2O2, particularly that measured in the presence of DNP (48% of control). DEM treatment did not significantly affect the respiratory inhibition by H2O2, whereas the degree of inhibition was somewhat greater following EA or AT treatment. By contrast, the sensitivity of cellular respiration to H2O2 was potentiated approximately two orders of magnitude by the permeabilization of sarcolemmal membrane; thus, 100 microM H2O2 inhibited both DNP-stimulated and unstimulated respiration to 17% and 35% of control, respectively. The results indicate that factors existing in the sarcolemma and/or in the cytosol, which become ineffective and/or are diluted, respectively, following permeabilization with saponin, are important cellular defense mechanisms in alleviating the toxic effect of exogenous H2O2 on the respiration of mitochondria in situ in myocytes. PMID- 1520250 TI - Exogenous fructose-1,6-bisphosphate is a metabolizable substrate for the isolated normoxic rat heart. AB - Isolated rat hearts were perfused by the recirculating Langendorff mode under normoxic conditions for 60 min. The Krebs-Ringer buffer was supplemented with 10 mM glucose + 12 IU/l insulin and either [U-14C]-fructose-1,6-bisphosphate (together with 5 mM cold fructose-1,6-bisphosphate) or [U-14C]-fructose (together with 5 mM cold fructose). At the end of perfusion, gaseous 14CO2, 14CO2 trapped in the perfusates, 14C-lactate output and tissue 14C-lactate were assayed in both groups of hearts. Analysis of high-energy compounds, glycogen, lactate, and pyruvate was also performed on the neutralized perchloric acid extracts of the freeze-clamped hearts. Data obtained from the 14C catabolites, originating from the metabolism of the radiolabeled substrates, indicated that the isolated normoxic rat heart metabolizes an 8.5 times higher amount of fructose-1,6 bisphosphate (7.07 mumoles/min/g d.w.) than of fructose (0.83 mumoles/min/g d.w.). CrP, CrP/Cr, glycogen, and total lactate in both tissue and perfusate were significantly higher in fructose-1,6-bisphosphate-perfused hearts. The overall indication is that fructose-1,6-bisphosphate can be taken up in its intact form by myocytes and successively metabolized to support their energy demand, and that its effects on myocardial performance and metabolism should be attributed to the molecule itself rather than to its eventual degradation products. PMID- 1520251 TI - Coronary autoregulation and optimal myocardial oxygen utilization. AB - The complex relationship among myocardial contractility, preload, afterload, and coronary autoregulation was studied using both analytical and numerical methods. To study autoregulation and coronary reserve changes in response to changes in cardiac oxygen consumption and in arterial pressure generation, a new variable was introduced: myocardial resistance to oxygen flow (RO2). This variable was defined as the ratio of the coronary driving pressure to left-ventricular oxygen uptake. High values for this variable indicate small consumption relative to the generated aortic pressure. Conditions which produce the highest obtainable value for RO2 are considered as optimal. An expression relating RO2 to ventricular hemodynamic variables was developed and studied using a mathematical model of the cardiovascular system. The model included a mechanism of local autoregulation based on the assumption that, in steady state, the amount of oxygen consumed equals the amount extracted from coronary blood. Heart rate, peripheral resistance, end-diastolic volume, and myocardial contractility were varied while the coronary circulation was adjusted to meet ventricular oxygen consumption at each state. The model predicts that, for each state of the circulation, there is an optimal level of cardiac contractility for which the coronary reserve is maximized. PMID- 1520252 TI - Identification of two distinct amplifications of the esterase B locus in Culex pipiens (L.) mosquitoes from Mediterranean countries. AB - Two new highly active esterases were detected by starch electrophoretic studies in Culex pipiens mosquitoes from the area of Montpellier (France) and from Cyprus. We demonstrate here that both the French and the Cyprus esterases B are overproduced due to amplification of the coding gene. The production of the esterase B is approximately 50- and 500-fold higher in mosquitoes from France and Cyprus, respectively, than in susceptible insects, whereas the number of gene copies is about 25 and 250. Differences of about 7- and 95-fold were also found in the degree of chlorpyrifos resistance. RFLP comparison of the amplified region containing the esterase B gene revealed large differences between French and Cyprus mosquitoes. It thus appears that two distinct haplotypes with an esterase B gene coding an enzyme with identical electrophoretic mobility have been amplified. We therefore named the haplotypes in mosquitoes from France and Cyprus B4 and B5, respectively. The estimated genetic distance between these two haplotypes is not smaller than those observed in all pair comparisons of other known esterase B haplotypes. These results are discussed in the context of amplification phenomena. PMID- 1520253 TI - Evidence for a genetic duplication involving alcohol dehydrogenase genes in Ceratitis capitata. AB - An Adh duplication is described in the medfly Ceratitis capitata. Evidence is presented for two separate Adh1 and Adh2 structural loci mapping at a distance of 0.49 recombination unit from each other. By deletion mapping the Adh region has been cytologically located near the free end of the left arm of the second chromosome within an area between 2C;3A segments of the polytene chromosome. The genetic analysis of the region around Adh has identified seven neighboring genes (Acon1, Mpi, Est6, Aox, Xdh, Mdh2, Lsp1) which identify the linkage group D. The orientation of loci with regard to the centromere sets the origin of the map of the left arm of the second chromosome close to the two Adh loci. PMID- 1520254 TI - Characterization of two electrophoretic lactate dehydrogenase-A mutants in Mus musculus. AB - Two lactate dehydrogenase (LDH) mutations were recovered independently among offspring of ethylnitrosourea-treated male mice by screening for alterations of isoelectric focusing pattern in liver homogenates. Investigations of physicochemical and kinetic properties of the mutant enzymes indicated that the mutant traits resulted from point mutations at the Ldh-1 structural locus. Therefore, the new alleles were designated Ldh-1a-m5Neu and Ldh-1a-m6Neu, respectively. Both mutant alleles code for proteins which exhibit an altered stability to heat, in addition to changes in isoelectric focusing pattern and a reduction in anodal electrophoretic mobility. While LDH-Aa-m5Neu proteins are markedly less heat stable, LDH-Aa-m6Neu proteins are more heat stable than the wild-type enzyme. Furthermore, a small elevation of Km for pyruvate, a slightly reduced inhibition by high pyruvate concentrations, and a slight acidic shift of the pH activity profile distinguish LDH-Aa-m6Neu from both wild-type and LDH-Aa m5Neu enzymes. Significant alterations of LDH activity were detected in some tissues from LDH-Aa-m5Neu individuals but not in those from LDH-Aa-m6Neu animals. Erythrocytes and blood of LDH-Aa-m5Neu mutants revealed activity levels which were reduced by approximately 6 and 13% compared with those of wild types in heterozygous and homozygous individuals, respectively. In addition, an elevation of approximately 6% in LDH activity was found in skeletal muscle in homozygous mutants. Consistent with the unaltered or only slightly altered LDH activity in tissues, the genetic as well as the physiological characterization yielded no easily detectable effects from either mutation on metabolism or fitness of the affected individuals. PMID- 1520255 TI - Drosophila acetylcholinesterase: characterization of different mutants resistant to insecticides. AB - Selection of field populations originating from several countries allowed us to isolate 13 strains of Drosophila melanogaster resistant to parathion. In vitro studies of acetylcholinesterase inhibition by paraoxon have been carried out on purified enzymes: most of the resistant strains harbor an altered acetylcholinesterase. Enzymes with higher resistance levels have been characterized with respect to their cross-resistance toward several insecticides. The patterns obtained have permitted us to group them and to delineate four categories. The existence of four distinct types of protein suggests that several mutations of acetylcholinesterase are responsible for insecticide resistance in Drosophila. PMID- 1520256 TI - Duplication of the structural gene for glucosephosphate isomerase and phosphogluconate dehydrogenase in Scabiosa columbaria and their phylogenetic implications in the dipsacaceae. AB - Zymograms of glucosephosphate isomerase (GPI) and phosphogluconate dehydrogenase (PGD) revealed three isozymes for each enzyme in the plant species Scabiosa columbaria. Intergenic heterodimers are formed between the polypeptides coded by Gpi-1 and Gpi-2 and between those coded by Pgd-1 and Pgd-2, indicating that a GPI and a PGD locus have been duplicated in the past. The ancestral genes assort independently with their duplicated gene, suggesting that the duplications have originated from a process of translocation. Linkage was found only between Gpi-1 and Pgd-2 and between Gpi-2 and Pgd-1, suggesting that the duplicated loci were located on the same translocated chromosomal segment. Both duplications are present in all other examined species of Scabiosa and in Cephalaria and Knautia, two other genera of the Dipsacaceae. The genera Succisa and Dipsacus, also belonging to the Dipsacaceae, do not show Gpi-1 activity, making Gpi-2 and Pgd-1 the most likely ancestral genes. In Succisa, the isozymes of Gpi-1 and Gpi-2 either overlap or Gpi-1 has been silenced. The combined results suggest that a chromosomal segment containing Gpi-2 and Pgd-1 has been translocated before the divergence of Scabiosa, Cephalaria, Knautia, and Succisa. PMID- 1520257 TI - Some ribosome-inactivating proteins depurinate ribosomal RNA at multiple sites. AB - Saporin-S6, a ribosome-inactivating protein (RIP) from Saponaria officinalis released more than 1 mol of adenine/mol of ribosomes from house fly (Musca domestica) larvae and from rat liver. The release of adenine from rat liver ribosomes by several RIPs (plant enzymes with RNA N-glycosidase activity) was examined. Saporins, pokeweed antiviral protein from roots of Phytolacca americana (PAP-R), and trichokirin from Trichosanthes kirilowii seeds depurinated rat liver ribosomes at more than one site. Up to 33 mol of adenine were released from 1 mol of ribosomes. This property is not common to all RIPS. PMID- 1520258 TI - L-tryptophan uptake by segment-specific membrane vesicles from the proximal tubule of rabbit kidney. AB - 1. The mechanism of the renal transport of L-tryptophan by basolateral and luminal membrane vesicles prepared from either the pars convoluta or the pars recta of the rabbit proximal tubule was studied. The uptake of L-tryptophan by basolateral membrane vesicles from the pars convoluta was found to be an Na(+) dependent transport event. The Na(+)-conditional influx of the amino acid was stimulated in the presence of an inwardly directed H+ gradient. Lowering the pH without an H+ gradient had no effect, indicating that L-tryptophan is co transported with H+. 3. On the other hand, no transient accumulation of L tryptophan was observed in the presence or absence of Na+ in basolateral membrane vesicles from the pars recta. 4. In luminal membrane vesicles from the pars recta, the transient Na(+)-dependent accumulation of L-tryptophan occurred via a dual transport system. In addition, an inwardly directed H+ gradient could drive the uphill transport of L-tryptophan into these vesicles in both the presence and the absence of an Na+ gradient. 5. By contrast, the uptake of L-tryptophan by luminal membrane vesicles from the pars convoluta was a strictly Na(+)-dependent and electrogenic transport process, mediated by a single transport component. 6. Investigation of the coupling ratio in luminal membrane vesicles suggested that 1 Na+:1 L-tryptophan are co-transported in the pars convoluta. In the pars recta, examination of the stoichiometry indicated that approx. 1 H+ and 2 Na+ (high affinity) or 1 Na+ (low affinity) are involved in the uptake of L-tryptophan. PMID- 1520259 TI - Structural and functional microheterogeneity of rat thyroxine-binding globulin during ontogenesis. AB - Thyroxine-binding globulin (TBG), the major carrier of thyroid hormones in human and murine sera, is in the rat a developmentally regulated protein, showing a large surge during post-natal growth followed by virtual disappearance in adults. Here we study as a function of age, from the 19-day embryo to 60 days after birth, the structural and binding characteristics of rat TBG microheterogeneity. Serum obtained throughout development, when pre-incubated with 125I-thyroxine (T4), was shown by isoelectric focusing (IEF; pH range 4-5) to contain six labelled isoforms of TBG, with isoelectric points between 4.25 and 4.55. These isoforms differ in their sialic acid content. The relative labelling densities of the isoforms show age-related changes: in neonates, the bulk of T4 is bound to the most alkaline (least sialylated) TBG isoforms; then, with advancing age, it shifts to the most acidic isoforms. To understand whether this progressive transfer of ligand reflects developmental changes in the relative abundance of isoforms, we submitted sera from rats of different ages to crossed immunoelectrofocusing analysis. We demonstrate that the relative proportions of the TBG isoforms remain fairly constant, independent of the level of total TBG. The most acidic forms always represented the majority (approximately 50%), with the most alkaline ones only representing 15% of total TBG. Experiments based on IEF of charcoal-treated sera, supplemented or not with lipidic serum extracts, further demonstrate that the paradoxical low labelling seen in the neonates for the most abundant highly sialylated isoforms is due to inhibition of their binding abilities by liposoluble components, which are particularly concentrated in the sera at the earlier post-natal ages. These studies represent the first analysis of concentration versus binding functions of rat TBG isoforms in the physiological conditions of normal ontogeny. Our results point to an important influence for the serum environment on the binding properties of TBG isoforms. The physiological significance of such interactions remains to be clarified. PMID- 1520260 TI - Exocytosis from permeabilized lactating mouse mammary epithelial cells. Stimulation by Ca2+ and phorbol ester, but inhibition of regulated exocytosis by guanosine 5'-[gamma-thio]triphosphate. AB - Lactating mouse mammary epithelial cells secrete large amounts of milk protein via constitutive or regulated exocytotic pathways. Secretion through both pathways was quantified by assaying the release of [35S]methionine-labelled trichloroacetic acid-precipitable proteins from digitonin-permeabilized secretory acini isolated from mammary glands of 10-day-post-partum lactating mice. Protein secretion from the isolated permeabilized cells was either Ca(2+)-dependent (regulated) or Ca(2+)-independent (constitutive). In both cases there was a requirement for ATP. Addition of the phorbol ester phorbol 12-myristate 13 acetate (PMA) caused a marked increase in the percentage protein secretion from the cells in a Ca(2+)-independent manner. However, the non-hydrolysable GTP analogue guanosine 5'-[gamma-thio]triphosphate (GTP[S]) caused a partial inhibition of Ca(2+)-dependent exocytosis, while having no significant effect on Ca(2+)-independent exocytosis. Thus the GTP[S] is exerting its effect on the regulated pathway at a site subsequent to protein sorting and packaging into secretory vesicles at the trans-Golgi network. PMID- 1520261 TI - Structural and electron-microscopic studies of jacalin from jackfruit (Artocarpus integrifolia) show that this lectin is a 65 kDa tetramer. AB - The 133-amino-acid sequences of the alpha-subunit of jacalin (a lectin from Artocarpus integrifolia) and of the slightly larger alpha'-subunit were determined. The alpha'- and alpha-subunits, in the approximate ratio of 1:3, were found to be virtually identical in their primary structures, except for one valine for isoleucine substitution at position 113. Although both alpha'- and alpha-chains were glycosylated, the extent of glycosylation in the alpha'-chain was much greater than that in the alpha-subunit. In the alpha'-polypeptide, all molecules contained an N-linked oligosaccharide at position 74 and some contained sugar at position 43. The alpha- and alpha'-subunits were found to be strongly non-covalently associated with three distinct beta-subunits containing 20 amino acids each. Electron-microscopic visualization of native jacalin disclosed a structure composed of four alpha-type subunits with a clear-cut 4-fold symmetry. Analytical-ultracentrifugation studies of jacalin revealed an average molecular mass of 65 kDa, a value compatible with a tetrameric structure of the alpha(alpha')-subunits. The recalculated number of sugar-binding sites per jacalin molecule, given a molecular mass of 65 kDa, would yield 0.8 sites per alpha(alpha')-promoter, i.e. about twice the value previously determined [Appukutan & Basu (1985) FEBS Lett. 180, 331-334; Ahmed & Chatterjee (1989) J. Biol. Chem. 264, 9365-9372]. PMID- 1520262 TI - Transfer of deuterium from [1,1-2H2]ethanol to steroids and organic acids in the rat testis. AB - Rats were given [1,1-2H2]ethanol in a single dose, and the 2H content was determined in testicular steroids and in organic acids of low molecular mass in the testis, liver and blood. The acids were quantified by capillary gas chromatography/mass spectrometry of t-butyldimethylsilyl derivatives with [2H4]lactate as internal standard. In addition to lactate, pyruvate, 3 hydroxybutyrate and acids of the tricarboxylic acid cycle, the testis was shown to contain 2-hydroxybutyrate, 2-hydroxy-2-methylbutyrate, 2-hydroxyisohexanoate and glycerate. No 2H was found in pregnenolone, 5-androstene-3 beta,17 beta-diol or testosterone, whereas the abundance of monodeuterated molecules of 5 alpha androstane-3 alpha,17 beta-diol and its 3 beta-isomer were 7.6% and 11.2% respectively. The abundance of monodeuterated lactate was 7.0% in the testis and 5.3% in the blood. The other acids were less labelled but 3-hydroxybutyrate had a higher 2H content in the testis (3.1%) than in the liver. These results support the contention that ethanol is oxidized in an alcohol dehydrogenase-catalysed reaction in testis in vivo and that the acute inhibition of the testosterone production is due at least partly to a redox effect. The labelling and increased concentration of 3-hydroxybutyrate in the testis indicate that a change in the mitochondrial redox state might be involved. PMID- 1520263 TI - Glucose regulates its transport in L8 myocytes by modulating cellular trafficking of the transporter GLUT-1. AB - The effect of culture conditions simulating hypo- and hyper-glycaemia on glucose transport and on the subcellular localization of the glucose transporter GLUT-1 was studied in L8 myocytes. Incubation of the cells with 20 mM-glucose for 25 h decreased the rate of 2-deoxy-D-[3H]glucose (dGlc) uptake to 0.106 +/- 0.016 nmol/min per 10(6) cells compared with 0.212 +/- 0.025 in cells maintained at 2 mM-glucose (final glucose concentrations at the end of the incubation period were 16-17 mM and 0.7-1.0 mM respectively). An additional 5 h incubation of these cells with medium containing the opposite glucose concentration (i.e. change from 17 mM to 1 mM and from 1 mM to 17 mM) increased the transport rate to 0.172 +/- 0.033 nmol/min per 10(6) cells in cultures initially conditioned at high glucose, and decreased the transport to 0.125 +/- 0.029 in those conditioned at low glucose. Plasma-membrane- and microsomal-membrane-enriched fractions were prepared from these cells for [3H]cytochalasin B (CB) binding and Western-blot analysis with antibodies against GLUT-1 and GLUT-4. A decrease in glucose concentration increased the number of D-glucose-displaceable CB-binding sites and GLUT-1 protein in the plasma-membrane fraction to the same extent as the increase in dGlc transport. Under downregulatory conditions, the lower dGlc-transport capacity could be accounted for by a decreased number of transporters in the plasma membrane of the cells. No apparent modification of the intrinsic activity of the glucose transporters was observed in up- or down-regulated cells. Under downregulatory conditions, the CB-binding data indicated a large increase in the number of transporters in the intracellular membranes of the myocytes. Western blots of the same membranes also indicated an increase in GLUT-1 content. However, the interaction of the intracellular GLUT-1 protein with the polyclonal antibodies was much weaker than that of the plasma-membrane-associated GLUT-1. The GLUT-4 concentration was too low to permit quantification in membrane fractions. Our findings suggest that autoregulation of glucose transport in L8 myocytes is accompanied by parallel changes in the number of GLUT-1 transporters in the plasma membrane, and that the rate of transporter degradation may be augmented in the upregulated myocytes. These glucose-induced changes are fully reversible. PMID- 1520265 TI - Isolation of a novel protein from the outer layer of the vitelline membrane. AB - The outer layer of the vitelline membrane from hen egg yolk consists of ovomucin, vitelline membrane outer layer protein I (VMOI) and lysozyme. Here we report the occurrence of a further basic protein (pI 11.5) in the outer layer, which was designated as vitelline membrane outer layer protein II (VMOII). It was dissociated from the outer layer in a 10% (w/v) NaCl solution and purified to homogeneity by ion-exchange chromatography. VMOII is a simple protein with a molecular mass of 6000 Da, as determined by sedimentation equilibrium analysis. The amino acid composition of VMOII was characterized by the absence of Met and high contents of cystine (half) (14%) and basic amino acids (6% Arg, 6% Lys and 3% His). Analysis of carboxymethylated VMOII indicated that all cysteine residues were involved in disulphide bonding, which appears to facilitate the binding of SDS to the protein. Sequence comparison of the N-terminal 20 residues revealed no identity with other known proteins. VMOII contained a small amount of alpha-helix and was quite resistant to heat denaturation. PMID- 1520264 TI - Characterization by rapid-kinetic and equilibrium methods of the interaction between N-terminally truncated forms of chicken cystatin and the cysteine proteinases papain and actinidin. AB - The interaction between five N-terminally truncated forms of chicken cystatin (starting at Leu-7, Leu-8, Gly-9, Ala-10 and Asp-15) and the cysteine proteinases papain and actinidin was studied by spectroscopic, kinetic and equilibrium methods. The u.v. absorption, near-u.v. c.d. and fluorescence emission difference spectra for the interactions with papain were all similar to the corresponding spectra for intact cystatin. The second-order association rate constants at 25 degrees C, pH 7.4, I 0.15, for the binding of the truncated forms to papain varied about 2-fold, from 6 x 10(6) to 1.5 x 10(7) M-1.s-1, and were comparable to the value of 9.9 x 10(6) M-1.s-1 for intact cystatin. In contrast, the rate constants for the dissociation of the complexes with papain increased markedly with increasing extent of truncation, from 7.5 x 10(-6)s-1 for Leu7 cystatin (a truncated form of cystatin having Leu-7 as its N-terminal amino acid) to 1.6s-1 for Ala10-cystatin, whereas the dissociation rate constants for the latter form and Asp15-cystatin were similar. Consequently, the binding affinities between the truncated cystatins and papain decreased in an analogous manner, as was also shown for the interaction with actinidin by equilibrium measurements. Studies of the binding of the truncated cystatins to inactivated papains indicated that small substituents on the active-site cysteine of the enzyme can be accommodated in the complex without any loss of affinity when the N-terminal segment of the inhibitor is removed. Taken together, the results suggest that in the N-terminal region of chicken cystatin only residues preceding Ala-10 participate in the interaction with proteinases. Of these residues, Leu-7 and Leu-8 together account for about two-thirds of the unitary free energy of binding contributed by the N terminal region, the relative importance of the two residues being dependent on the target proteinase. Both Gly-9 and residues N-terminal of Leu-7 further stabilize the interaction but contribute substantially smaller binding energies than do the two leucine residues. PMID- 1520266 TI - Cloning and expression of a hepatic microsomal glucose transport protein. Comparison with liver plasma-membrane glucose-transport protein GLUT 2. AB - Antibodies raised against a 52 kDa rat liver microsomal glucose-transport protein were used to screen a rat liver cDNA library. Six positive clones were isolated. Two clones were found to be identical with the liver plasma-membrane glucose transport protein termed GLUT 2. The sequence of the four remaining clones indicates that they encode a unique microsomal facilitative glucose-transport protein which we have termed GLUT 7. Sequence analysis revealed that the largest GLUT 7 clone was 2161 bp in length and encodes a protein of 528 amino acids. The deduced amino acid sequence of GLUT 7 shows 68% identity with the deduced amino acid sequence of rat liver GLUT 2. The GLUT 7 sequence is six amino acids longer than rat liver GLUT 2, and the extra six amino acids at the C-terminal end contain a consensus motif for retention of membrane-spanning proteins in the endoplasmic reticulum. When the largest GLUT 7 clone was transfected into COS 7 cells the expressed protein was found in the endoplasmic reticulum and nuclear membrane, but not in the plasma membrane. Microsomes isolated from the transfected COS 7 cells demonstrated an increase in their microsomal glucose transport capacity, demonstrating that the GLUT 7 clone encodes a functional endoplasmic-reticulum glucose-transport protein. PMID- 1520267 TI - The transcriptional tissue specificity of the human pro alpha 1 (I) collagen gene is determined by a negative cis-regulatory element in the promoter. AB - The transcriptional activity of plasmid pCOL-KT, in which human pro alpha 1 (I) collagen gene upstream sequences up to -804 and most of the first intron (+474 to +1440) drive expression of the chloramphenicol acetyltransferase (CAT) gene [Thompson, Simkevich, Holness, Kang & Raghow (1991) J. Biol. Chem. 266, 2549 2556], was tested in a number of mesenchymal and non-mesenchymal cells. We observed that pCOL-KT was readily expressed in fibroblasts of human (IMR-90 and HFL-1), murine (NIH 3T3) and avian (SL-29) origin and in a human rhabdomyosarcoma cell line (A204), but failed to be expressed in human erythroleukaemia (K562) and rat pheochromocytoma (PC12) cells, indicating that the regulatory elements required for appropriate tissue-specific expression of the human pro alpha 1 (I) collagen gene were present in pCOL-KT. To delineate the nature of cis-acting sequences which determine the tissue specificity of pro alpha 1 (I) collagen gene expression, functional consequences of deletions in the promoter and first intron of pCOL-KT were tested in various cell types by transient expression assays. Cis elements in the promoter-proximal and intronic sequences displayed either a positive or a negative influence depending on the cell type. Thus deletion of fragments using EcoRV (nt -625 to -442 deleted), XbaI (-804 to -331) or SstII (+670 to +1440) resulted in 2-10-fold decreased expression in A204 and HFL-1 cells. The negative influences of deletions in the promoter-proximal sequences was apparently considerably relieved by deleting sequences in the first intron, and the constructs containing the EcoRV/SstII or XbaI/SstII double deletions were expressed to a much greater extent than either of the single deletion constructs. In contrast, the XbaI* deletion (nt -804 to -609), either alone or in combination with the intronic deletion, resulted in very high expression in all cells regardless of their collagen phenotype; the XbaI*/(-SstII) construct, which contained the intronic SstII fragment (+670 to +1440) in the reverse orientation, was not expressed in either mesenchymal or nonmesenchymal cells. Based on these results, we conclude that orientation-dependent interactions between negatively acting 5'-upstream sequences and the first intron determine the mesenchymal cell specificity of human pro alpha 1 (I) collagen gene transcription. PMID- 1520268 TI - Effects of organic anions on biliary lipid secretion in rats. Importance of association with biliary lipid structures. AB - This study was performed to determine the effects of various organic anions on biliary lipid secretion in rats. We infused bile-salt-pool-depleted rats with sodium taurocholate at a constant rate, with or without various organic anions: Indocyanine Green (ICG), bromosulphophthalein (BSP), BSP-glutathione and Phenol Red (PR). BSP decreased biliary secretion of cholesterol and phospholipids in a dose-dependent manner without affecting bile salt secretion (uncoupling), and this change was fully reversible. In contrast, ICG, BSP-glutathione and PR did not cause such an uncoupling of biliary lipids. In addition, the distribution pattern of each organic anion to various lipid particles was determined by gel permeation chromatography. BSP was predominantly associated with bile salt micelles, whereas vesicular association was dominant for ICG, and both BSP glutathione and PR formed only self-aggregations. From these data, we concluded that the uncoupling of biliary lipids from bile salt secretion by BSP resulted from the interaction between BSP and bile salt micelles in the bile canaliculus, and that this interaction inhibited the capacity of bile salts to induce the secretion of phospholipids and cholesterol. PMID- 1520269 TI - Site-directed mutagenesis and chemical modification of cysteine residues of rat glutathione S-transferase 3-3. AB - Rat liver glutathione S-transferase (GST) 3-3 is composed of two identical subunits, each containing three cysteine residues, Cys-86, Cys-114 and Cys-173. We have shown previously that Cys-86 is not involved in the enzymic activity of GST 3-3 [Hsieh, Huang, Chen, Lai & Tam (1991) Biochem, J. 278, 293-297]. At 50 degrees C, iodoacetamide can inactivate the enzyme by modifying Cys-86 and Cys 114. Cys-114 can be protected against iodoacetamide inhibition by S (dinitrophenyl)glutathione. Site-directed mutagenesis was used to construct mutants in which serine replaced one (C114S and C173S) or all three (CallS) cysteine residues. These mutants were over-expressed in Spodoptera frugiperda cells in a baculovirus system and were found to be fully active. Replacing Cys-86 or Cys-114 with alanine (C86A and C114A) does not diminish the activity of the protein. The results suggest that cysteines are not involved in the enzymic mechanism, and Cys-114 is possibly located at the active site of GST 3-3. PMID- 1520270 TI - Insulin-stimulated phosphorylation of calmodulin. AB - Calmodulin is phosphorylated in vitro by the insulin-receptor tyrosine kinase and a variety of serine/threonine kinases. Here we report that insulin stimulates the phosphorylation of calmodulin on average 3-fold in intact rat hepatocytes. Although calmodulin is constitutively phosphorylated, insulin increases phosphate incorporation into serine, threonine and tyrosine residues. We demonstrate that casein kinase II, an insulin-sensitive kinase, phosphorylates calmodulin in vitro on serine/thyronine residues (Thr-79, Ser-81, Ser-101 and Thr-117). The ability of the insulin receptor to phosphorylate calmodulin that has been pre phosphorylated by casein kinase II is enhanced up to 35-fold, and the sites of phosphorylation on calmodulin are shifted from tyrosine to threonine and serine. These observations, obtained with a new specific monoclonal antibody to calmodulin, confirm that insulin stimulates calmodulin phosphorylation in intact cells. The observation that calmodulin is phosphorylated in vivo, coupled with the recent demonstration that phosphocalmodulin exhibits altered biological activity, strongly suggests that phosphorylation of calmodulin is a critical component of intracellular signalling. PMID- 1520271 TI - Hydrolysis of rat melanin-concentrating hormone by endopeptidase 24.11 (neutral endopeptidase). AB - Melanin-concentrating hormone (MCH) is a cyclic peptide which behaves as an antagonist of the pituitary melanotropic hormone alpha-melanocyte-stimulating hormone in fishes. Cloning of the rat MCH cDNA precursor recently revealed the presence of an additional putative peptide named NEI. The present work examined the susceptibility of these novel peptides to hydrolysis by various purified exo- and endo-peptidases including endopeptidases 24.11 (NEP), 24.15, 24.16, angiotensin-converting enzyme, leucine aminopeptidase and carboxypeptidase A. NEP attacked MCH at three sites of the molecule with an apparent affinity of about 12 microM and a kcat. of 4 min-1. The first site of cleavage was at Cys-7-Met-8, i.e. within the peptide loop formed by the internal disulphide bridge. NEP could therefore be considered as an MCH-inactivating peptidase since the degradation products generated are probably devoid of biological activity. In contrast, NEI neither inhibited the degradation of the NEP chromogenic substrate glutaryl-Phe Ala-Phe-p-aminobenzoate nor was susceptible to proteolysis by NEP. Unlike NEP, angiotensin-converting enzyme, endopeptidase 24.15 and endopeptidase 24.16 appeared totally unable to cleave MCH, whereas the peptide was readily degraded by aminopeptidase M and carboxypeptidase A. PMID- 1520272 TI - Kinetic analysis of the type-1 proinsulin endopeptidase by a monoclonal antibody based immunoadsorbent assay. AB - A simple, rapid and sensitive assay for the type-1 endopeptidase (Arg-Arg cleaving) was developed by using an antiproinsulin monoclonal immunoadsorbent to separate reaction products from the substrate. The values obtained by this assay were identical with those obtained by an h.p.l.c.-based procedure and yielded similar values for the pH optimum (5.6) and Ca2+ activation (K0.5 = 2 mM). It was shown that the type-1 endopeptidase was readily solubilized by Triton X-114 (87 +/- 3%, n = 12) and partitioned principally into the aqueous phase at 30 degrees C (90.1 +/- 2.6%, n = 12). Activity was lost on gel filtration, but could be restored by adenosine 5'-[gamma-thio]triphosphate (K0.5 = 6 microM), 50 microM dithiothreitol or 50 microM-Ca(2+)-trans-1,2-diaminocyclohexane-NNN'N'-tetra acetic acid (CDTA), indicating that the enzyme was particularly sensitive to heavy metal ions. The Km obtained with proinsulin as substrate (13 +/- 1.7 microM) indicated that the enzyme works at close to its Vmax. in the nascent secretory granule. The Vmax. of the enzyme prepared from insulin granules (0.6% proinsulin converted/min) corresponded closely to the rate measured in vivo in rat islets. The type-1 endopeptidase also appears to be capable of binding to proinsulin in the region of the C-peptide/A-chain junction, since a peptide spanning this region was found to inhibit the 125I-proinsulin processing measured by this assay. PMID- 1520273 TI - Molecular mechanism of uncompetitive inhibition of human placental and germ-cell alkaline phosphatase. AB - Placental (PLAP) and germ-cell (GCAP) alkaline phosphatases are inhibited uncompetitively by L-Leu and L-Phe. Whereas L-Phe inhibits PLAP and GCAP to the same extent, L-Leu inhibits GCAP 17-fold more strongly than it does PLAP. This difference has been attributed [Hummer & Millan (1991) Biochem. J 274, 91-95] to a Glu----Gly substitution at position 429 in GCAP. The D-Phe and D-Leu enantiomorphs are also inhibitory through an uncompetitive mechanism but with greatly decreased efficiencies. Replacement of the active-site residue Arg-166 by Ala-166 changes the inhibition mechanism of the resulting PLAP mutant to a more complex mixed-type inhibition, with decreased affinities for L-Leu and L-Phe. The uncompetitive mechanism is restored on the simultaneous introduction of Gly-429 in the Ala-166 mutant, but the inhibitions of [Ala166,Gly429]PLAP and even [Lys166,Gly429]PLAP by L-Leu and L-Phe are considerably decreased compared with that of [Gly429]PLAP. These findings point to the importance of Arg-166 during inhibition. Active-site binding of L-Leu requires the presence of covalently bound phosphate in the active-site pocket, and the inhibition of PLAP by L-Leu is pH-sensitive, gradually disappearing when the pH is decreased from 10.5 to 7.5. Our data are compatible with the following molecular model for the uncompetitive inhibition of PLAP and GCAP by L-Phe and L-Leu: after binding of a phosphorylated substrate to the active site, the guanidinium group of Arg-166 (normally involved in positioning phosphate) is redirected to the carboxy group of L-Leu (or L-Phe), thus stabilizing the inhibitor in the active site. Therefore leucinamide and leucinol are weaker inhibitors of [Gly429]PLAP than is L-Leu. During this Arg-166 regulated event, the amino acid side group is positioned in the loop containing Glu-429 or Gly-429, leading to further stabilization. Replacement of Glu-429 by Gly-429 eliminates steric constraints experienced by the bulky L-Leu side group during its positioning and also increases the active-site accessibility for the inhibitor, providing the basis for the 17-fold difference in inhibition efficiency between PLAP and GCAP. Finally, the inhibitor's unprotonated amino group co-ordinates with the active-site Zn2+ ion 1, interfering with the hydrolysis of the phosphoenzyme intermediate, a phenomenon that determines the uncompetitive nature of the inhibition. PMID- 1520274 TI - A sub-population of keratan sulphates derived from bovine articular cartilage is capped with alpha(2-6)-linked N-acetylneuraminic acid residues. Affinity chromatography using immobilized Sambucus nigra lectin and characterization using 1H n.m.r. spectroscopy. AB - Alkaline borohydride-reduced keratan sulphate (KS) chains derived from bovine femoral head cartilage were fractionated by lectin affinity chromatography with Sambucus nigra agglutinin (SNA) into binding and non-binding populations. Analysis of the SNA-binding and non-binding KS chains using 600 MHz 1H n.m.r. spectroscopy showed that the former population contained alpha(2-6)-N acetylneuraminic acid residues and the latter contained primarily alpha(2-3)-N acetylneuraminic acid residues as chain terminators. Both populations contained a similar proportion of alpha(2-3)-N-acetylneuraminic acid residues within their protein-linkage regions, and similar sulphation and fucosylation levels. Analysis of these two fractions by gel-permeation chromatography (g.p.c.) on a TSK-30 XL column showed them to have the same size distributions. It was concluded from the n.m.r. spectra and g.p.c. data that the populations differed primarily in the mode of linkage of the chain-terminating sialic acids. PMID- 1520275 TI - Degradation of articular cartilage keratan sulphates using hydrazinolysis and nitrous acid. Environment of fucose residues. AB - Alkaline borohydride-reduced keratan sulphate (KS) chains from bovine articular cartilage (6-8-year-old animals) were fragmented by an anhydrous hydrazine/nitrous acid procedure, previously used on KS by Hopwood & Elliott to isolate the major disaccharides from the poly-N-acetyl-lactosamine repeat sequence [Hopwood & Elliott (1983) Carbohydr. Res. 117, 263-274]. The resulting oligosaccharides were reduced with NaB3H4 or NaBH4 and subjected to ion-exchange chromatography on a Nucleosil 5SB column. In addition to the major disaccharides, two fucose-containing oligosaccharides were examined by high-field 1H n.m.r. spectroscopy, and shown to have the following structures (where AnManOH is 2,5 anhydro-D-mannitol): [formula: see text] It is evident that the presence of fucose protects the N-acetylglucosamine residue from de-N-acetylation, and therefore fragments are produced which preserve the immediate environment of the fucose residue. It may be of biosynthetic significance that these two oligosaccharides contain an unsulphated galactose on the non-reducing side of the fucose residue. The hydrazine/nitrous acid/NaB3H4 method followed by h.p.l.c. provides a sensitive fingerprinting technique for the assay of KS composition and sub-populations. PMID- 1520276 TI - Steady-state kinetic mechanism of bovine brain tubulin: tyrosine ligase. AB - The ATP-dependent resynthesis of tubulin from tyrosine and untyrosinated tubulin was examined to establish the most probable steady-state kinetic mechanism of the tubulin: tyrosine ligase (ADP-forming). Three pair-wise sets of initial rate experiments, involving variation of two substrates pair-wise with the third substrate held at a high (but non-saturating) level, yielded convergent-line data, a behaviour that is diagnostic for sequential mechanisms. Michaelis constants were 14 microM, 1.9 microM and 17 microM for ATP, untyrosinated tubulin and L-tyrosine respectively, and the maximal velocity was 0.2 microM/min. AMP was a competitive inhibitor with respect to ATP, and a non-competitive inhibitor versus either tubulin or tyrosine. Likewise, L-dihydroxyphenylalanine acted competitively relative to tyrosine and non-competitively with respect to either ATP or tubulin. These findings directly support a random sequential mechanism. Product inhibition patterns with ADP were also consistent with this assignment; however, inhibition studies were not practical with either orthophosphate or tyrosinated tubulin because both were very weak inhibitors. Substrate protection of the enzyme against alkylation by N-ethylmaleimide and thermal inactivation, along with evidence of enzyme binding to ATP-Sepharose and tubulin-Sepharose, also supports the idea that this three-substrate enzyme reaction exhibits a random substrate addition pathway. PMID- 1520277 TI - Binding of sorbitol 6-phosphate and of fructose 1-phosphate to the regulatory protein of liver glucokinase. AB - Using a binding assay in which the ligand-protein complex is separated from free ligand by precipitation with poly(ethylene glycol) 6000, we found that the regulatory protein of rat liver glucokinase bound close to 1 mol of radiolabelled sorbitol 6-phosphate, a negative effector, or of fructose 1-phosphate, a positive effector, per mol of regulatory protein. Scatchard plots were linear, the dissociation constant being 0.3 microM for both phosphate esters. Sorbitol 6 phosphate and fructose 1-phosphate competed with each other for the binding. Competition was also observed with psicose 1-phosphate, ribitol 5-phosphate, arabitol 5-phosphate and 3-phosphoglycerate, all of which are known to affect the inhibition exerted by the regulatory protein. At a concentration of 10%, poly(ethylene glycol) 6000 decreased the concentration of regulatory protein causing 50% inhibition to a larger extent in the absence (12-fold) than in the presence (3-fold) of a saturating concentration of fructose 6-phosphate, another negative effector. Furthermore, it increased by about 3-fold the apparent affinity for inhibitory phosphate esters, indicating that it induced conformational changes of the regulatory protein. PMID- 1520278 TI - Regulation of glutathione metabolism in Ehrlich ascites tumour cells. AB - Glutathione metabolism was studied in cancer cells during the growth of an Ehrlich ascites tumour. GSH, but not GSSG, content decreases when cell proliferation and the rate of protein synthesis in the tumour decrease. This change correlates with a decrease in the rate of GSH synthesis and an increase in glutathione peroxidase and glutathione S-transferase activities. Glutathione efflux from tumour cells seems to co-ordinate with the rate of GSH synthesis. Cysteine, and not methionine, promotes GSH synthesis in tumour cells. However, changes in the rate of GSH synthesis are not due to limitations in the supply of blood cysteine or to changes in the intracellular amino acid pool of the cancer cells. Our data suggest that changes in protein metabolism accompanying tumour growth in vivo can modulate glutathione content in cancer cells. PMID- 1520279 TI - Cell-free synthesis of enzymically active tissue-type plasminogen activator. Protein folding determines the extent of N-linked glycosylation. AB - Tissue-type plasminogen activator (t-PA) is synthesized in mammalian cells as a mixture of two forms that differ in their extent of N-linked glycosylation. We have investigated the mechanism underlying this variation in glycosylation, using a cell-free system that consists of a rabbit reticulocyte lysate optimized for the formation of disulphide bonds and supplemented with dog pancreas microsomal membranes. Molecules of human t-PA synthesized in vitro are enzymically active and responsive to natural activators and inhibitors, and are glycosylated in a pattern identical with that of the protein produced in vivo. This demonstrates that t-PA synthesized in vitro folds into the same conformation as the protein synthesized in vivo. We show that the extent of glycosylation of individual t-PA molecules is dependent on the state of folding of the polypeptide chain, since the probability of addition of an oligosaccharide side chain at Asn-184 is decreased under conditions that promote the formation of enzymically active molecules. This variation in glycosylation is independent of the rate of protein synthesis. PMID- 1520280 TI - Effect of pyrazole, cobalt and phenobarbital on mouse liver cytochrome P-450 2a 4/5 (Cyp2a-4/5) expression. AB - Pyrazole, cobalt and phenobarbital increase the activity of coumarin 7 hydroxylase (COH) in mouse liver. To study the mechanism of this increase, we measured the expression of the cytochrome P-450 2a-4/5 (Cyp2a-4/5) complex, which mediates testosterone 15 alpha-hydroxylase and COH activities, as a function of dose and time after the treatment of C57BL/6 (B6) and DBA/2 (D2) male mice with the inducers. COH activity and Cyp2a-4/5 steady-state mRNA levels were increased in both strains in response to the inducers. No marked effect occurred with testosterone 15 alpha-hydroxylase or activities associated with Cyp1a-1 or Cyp2e 1. A 2-7-fold increase in response to the inducers was seen in the amount of P 450Coh (cytochrome P-450 isoenzyme catalysing coumarin 7-hydroxylation) protein in Western immunoblots. PCR amplification of a 1 kb region in Cyp2a-4/5-mRNA derived cDNA, followed by cutting at the diagnostic PstI site, showed that most of the steady-state mRNA consisted of Cyp2a-5, which is also the form most affected by pyrazole. Nuclear run-off analysis revealed no increase in the transcription rate of Cyp2a-4/5 after pyrazole or cobalt treatment, whereas a 2-3 fold increase occurred after phenobarbital pretreatment in B6 mice. Together with previous reports [Aida & Negishi (1991) Biochemistry 30, 8041-8045], the current data suggest that both pyrazole and cobalt increase COH catalytic activity by affecting Cyp2a-5 by post-transcriptional mechanisms in mice. PMID- 1520281 TI - Eicosapentaenoic acid inhibits cell growth and triacylglycerol secretion in McA RH7777 rat hepatoma cultures. AB - The plasma triacylglycerol-decreasing effect of fish-oil fatty acids was studied in vitro by using the rapidly growing cultured rat hepatoma cell line McA-RH7777. Cells were exposed to albumin-complexed eicosapentaenoic acid (C20:5n-3; EPA), to oleic acid (C18:1n-9; OA), or to albumin alone. Cell growth was similar in albumin- and OA-supplemented cultures, but EPA treatment inhibited growth. As estimated by [14C]glycerol incorporation, OA stimulated both net triacylglycerol synthesis and secretion over control levels in a dose-dependent manner. EPA stimulated triacylglycerol synthesis in similar fashion to OA, but paradoxically decreased net triacylglycerol secretion and led to exaggerated intracellular accumulation of radiolabelled triacylglycerol. The EPA and OA effects were additive at low concentrations of total fatty acid, but at higher fatty acid concentrations OA appeared to negate some effects of EPA. Chemical analysis of albumin- and OA-treated cultures revealed OA-dominant profiles for both cellular and medium triacylglycerol-associated fatty acids. In contrast, EPA was the principal fatty acid in cellular triacylglycerol of EPA-supplemented cultures, whereas medium triacylglycerol from these cultures contained very little EPA. We conclude that McA-RH7777 hepatoma cells readily synthesize EPA-containing triacylglycerol molecules, but they have variable capacity for secreting them. We consider potential mechanisms to account for the effects of EPA in this system. PMID- 1520282 TI - Position-independent expression of the ovine beta-lactoglobulin gene in transgenic mice. AB - The major milk whey protein of sheep, beta-lactoglobulin (BLG), is expressed specifically in the mammary gland in a developmentally regulated pattern. To identify the cis-acting DNA regions involved in the regulation of BLG expression, resected gene constructs were analysed in transgenic mice. BLG transgenes which contain at least the proximal 406 bp of the 5' flanking region were expressed in all mice analysed, at levels related to transgene copy number, and thus were expressed in a position-independent manner. Expression was restricted to the mammary gland, except in a few lines where low-level expression was also detected in the salivary gland. In these mice, BLG transgenes were expressed during pregnancy and lactation in the appropriate temporal pattern. Further resection of the 5' proximal region to -146 bp resulted in a dramatically reduced frequency of expression, without affecting tissue specificity, while a construct which retained only 79 bp of 5' flanking region was not expressed. Chromatin analysis of isolated sheep nuclei showed that the promoter resides within a DNAaseI hypersensitive region in the mammary gland but not in the liver. A BLG transgene displayed a similar tissue-specific pattern of DNAaseI hypersensitivity in mice. These data demonstrate an essential role of the proximal DNAaseI-hypersensitive sequences for position-independent expression of the BLG gene. PMID- 1520283 TI - Substrate specificity of human liver neutral alpha-mannosidase. AB - The digestion of radiolabelled natural oligosaccharide substrates by human liver neutral alpha-mannosidase has been studied by h.p.l.c. and h.p.t.l.c. The high mannose oligosaccharides Man9GlcNAc and Man8GlcNAc are hydrolysed by the enzyme by two distinct non-random routes to a common product of composition Man6GlcNAc, which is then slowly converted into a unique Man5GlcNAc oligosaccharide, Man alpha(1----2)Man alpha(1----2)Man alpha(1----3)[Man alpha (1----6)] Man beta(1--- 4)GlcNAc. These pathways are different from the processing and lysosomal catabolic pathways for these structures. In particular, the alpha(1----2)-linked mannose residues attached to the core alpha(1----3)-linked mannose residue are resistant to hydrolysis. The key processing intermediate, Man alpha(1----3)[Man alpha(1----6)]Man alpha(1----6)[Man alpha(1----3)] Man beta(1----4)GlcNAc, is not produced in the digestion of high-mannose glycans by the neutral alpha mannosidase, but it is hydrolysed by the enzyme by a non-random route to Man beta(1----4)GlcNAc via the core structure Man alpha(1----3)[Man alpha(1----6)]Man beta(1----4)GlcNAc. In contrast with its ready hydrolysis by lysosomal alpha mannosidase, the core alpha(1----3)-mannosidic linkage is quite resistant to hydrolysis by neutral alpha-mannosidase. The precise specificity of neutral alpha mannosidase towards high-mannose oligosaccharides suggests that it has a role in the modification of such structures in the cytosol. PMID- 1520284 TI - Substrate specificity of the bovine and feline neutral alpha-mannosidases. AB - Neutral alpha-mannosidases were prepared from bovine and cat liver. The activities were distinguished from lysosomal and Golgi alpha-mannosidases by their neutral pH optima, relatively low Km for their synthetic substrate p nitrophenyl alpha-D-mannoside, inhibition by Zn2+ and absence of inhibition by Co2+, EDTA, low concentrations of swainsonine, or deoxymannojirimycin. The cytosolic alpha-mannosidases were not retained by concanavalin A-Sepharose. They were able to degrade efficiently a variety of oligosaccharides with structures corresponding to certain high-mannose glycans or the oligomannosyl parts of hybrid and complex glycans. However, unlike lysosomal alpha-mannosidases from the same species these enzymes were not able to degrade Man9GlcNAc2 efficiently, and the bovine neutral alpha-mannosidase was not able to degrade a hexasaccharide with a structure analogous to Man5GlcNAc2-PP-dolichol. Sharp differences were noted for the bovine and cat enzymes with regard to the specificity of degradation. The bovine neutral alpha-mannosidase degraded the substrates by defined pathways, but the cat neutral alpha-mannosidase often produced complex mixtures of products, especially from the larger oligosaccharides. Therefore the bovine enzyme resembled the rat and human cytosolic alpha-mannosidases, but the cat enzyme did not. The bovine and cat neutral alpha-mannosidases, unlike the corresponding lysosomal activities, did not show specificity for the hydrolysis of the (1----3)- and (1----6)-linked mannose residues in the N-linked glycan pentasaccharide core. PMID- 1520285 TI - Further characterization of hormonal regulation of glutathione transferase in rat liver and adrenal glands. Sex differences and demonstration that growth hormone regulates the hepatic levels. AB - Immunoblot experiments and reverse-phase h.p.l.c. were used to study the levels of glutathione transferase subunits 1, 2, 3, 4, 6, 7 and 8 in the liver and adrenal of intact and hypophysectomized male and female Sprague-Dawley rats. A sexual dimorphism in the levels of several of these isoenzymes and in their responses to hypophysectomy was demonstrated. In the liver of sham-operated females and males there are differences in glutathione transferase activities and isoenzyme pattern. H.p.l.c. analysis showed higher levels of subunits 1, 3 and 4 in male rats compared with females. In contrast with the pronounced sex differences in sham-operated rats, the isoenzyme patterns of hypophysectomized males and females were very similar. In the adrenal glands, however, a sexual dimorphism became apparent only after hypophysectomy, when the level of subunit 4 was increased 14-fold in the female, whereas the corresponding increase in the male rat was only 2.7-fold. The hepatic pattern of glutathione transferase subunits could be altered by continuous infusion of growth hormone to both sham operated and hypophysectomized rats of both sexes. This treatment feminized the isoenzyme pattern in sham-operated males and a similar effect was obtained upon treating hypophysectomized rats with thyroxine, cortisone acetate and a continuous infusion of growth hormone. PMID- 1520286 TI - Collagen metabolism in cultured osteoblasts from osteogenesis imperfecta patients. AB - Collagen produced in vitro by bone cells isolated from 19 patients with different forms of osteogenesis imperfecta (OI) was analysed. Clinically, four patients were classified as OI type I, 10 patients as OI type III and five patients as OI type IV. Bone cells of 12 of the 19 OI patients produced structurally abnormal type I collagen. Electrophoretically uniformly slower migrating collagen type I alpha-chains were found in one case of OI type I, in seven cases of OI type III and in one case of OI type IV; two cultures of OI type III produced two different populations of collagen type I alpha-chains, and one culture of OI type IV showed reduction-sensitive dimer formation of alpha 1(I) chains, resulting from the inadequate incorporation of a cysteine residue into the triple helical domain of alpha 1(I). Quantitative analysis of collagen metabolism led to the distinction of two groups of cultured OI osteoblasts. In osteoblasts of OI type I, mainly production of collagen was decreased, whereas secretion, processing and pericellular accumulation of (pro)collagen type I was similar to that in control osteoblasts. In contrast, in osteoblasts of OI types III and IV, production as well as secretion, processing and pericellular accumulation of (pro)collagen type I were significantly decreased. Low levels of type I collagen were found irrespective of the presence or absence of structural abnormalities of collagen type I in all OI types. PMID- 1520287 TI - Positive co-operative interaction between the subunits of CeqI restriction endonuclease. AB - CeqI restriction endonuclease, an isoschizomer of EcoRV, forms complexes of 12-20 subunits under physiological conditions, in the absence of DNA. These molecules partially dissociate in the presence of DNA sequences recognized by CeqI or in the presence of non-ionic detergents. In solutions containing high concentrations of salts (e.g. 1 M-NaCl), the enzyme dissociates into subunits, concomitantly losing its activity. According to our experiments, it is the tetrameric form of the enzyme that binds the DNA and represents the catalytically active molecule. Analysis of the enzyme kinetics revealed a positive co-operative interaction between the subunits of the enzyme. Computer-assisted analysis of these data yielded a Hill coefficient of approx. 1.35, suggesting two binding sites per tetrameric enzyme molecule, two subunits per palindromic recognition site. PMID- 1520288 TI - Reconstitution of the human placental 5-hydroxytryptamine transporter in a catalytically active form after detergent solubilization. AB - The 5-hydroxytryptamine (5-HT; serotonin) transporter was solubilized from purified human placental brush border membranes by cholate in the presence of urea, and the solubilized transporter was reconstituted into proteoliposomes in a functionally active form. Solubilization of the membranes with cholate in the absence of urea inactivated the transporter. The reconstitution procedure involved precipitation of the solubilized proteins and simultaneous removal of cholate and urea by poly(ethylene glycol), and incorporation of the precipitated proteins into proteoliposomes in the presence of asolectin by a freeze thaw/sonication technique. Optimal conditions included the use of 6% poly(ethylene glycol) during the precipitation step and an asolectin/protein ratio of 10:1 during the reconstitution step. K+ was present in the reconstitution medium. The reconstituted proteoliposomes showed the ability to transport 5-HT against a concentration gradient when an inwardly directed NaCl gradient was imposed. The 5-HT transport system in the proteoliposomes had an absolute requirement for Na+ and Cl-. The system was specific for 5-HT and was inhibited by imipramine, paroxetine and fluoxetine. The Na+/Cl-/5-HT stoichiometry was found to be 1:1:1. The transport process was electrically silent, indicating that one K+ ion was countertransported for each 5-HT molecule. The reconstituted 5-HT transporter showed high affinity for 5-HT, with an apparent Michaelis-Menten constant of 0.34 +/- 0.01 microM. It is concluded that the human placental 5-HT transporter can be solubilized and reconstituted into proteoliposomes in a transport-competent form and that the characteristics of the reconstituted transporter are similar to those of the native transporter. PMID- 1520290 TI - A novel gene encoding a smooth muscle protein is overexpressed in senescent human fibroblasts. AB - In order to identify genes that may be causally involved in replicative senescence, we have isolated several gene sequences that are overexpressed in senescent human fibroblasts by differential screening of a cDNA library derived from mRNA of a subject with Werner syndrome of premature aging (Murano, S., et al., Molec. Cell. Biol., 3905-3914, 1991). Herein, we describe the sequence and expression of one of these genes, WS3-10, which encodes a novel human cytoplasmic protein of 22.5 kilodaltons. The steady-state mRNA levels of WS3-10 mRNA were higher in WS and late-passage normal cells compared to early-passage normal cells following serum depletion and subsequent repletion. Computer analysis showed similarities between WS3-10 and certain proteins in other species, indicating that WS3-10 represents the human homolog of a smooth muscle protein involved in calcium interactions that may contribute to replicative senescence. PMID- 1520291 TI - Identification of an amino acid residue involved in the substrate-binding site of rat liver uricase by site-directed mutagenesis. AB - Computer analysis has shown that a conserved amino acid sequence (Leu 160 to Lys 164) of rat liver uricase is also present in other enzymes with purine substrates. The significances of the amino acids in this sequence were studied by site-directed mutagenesis. Replacement of Lys 164 by Glu or Ile resulted in loss of uricase activity and decrease in binding of the competitive inhibitor xanthine. The far ultraviolet circular dichroic spectra of the mutant uricases were identical to that of the wild type protein, indicating that the replacement of Lys 164 by other amino acids did not result in serious modification of the conformation of uricase. These findings suggest that this amino acid is involved in the substrate-binding site of the enzyme. PMID- 1520289 TI - Reconstitution and characterization of a Na+/Pi co-transporter protein from rabbit kidney brush-border membranes. AB - A protein with Na+/Pi co-transporter activity has been extracted from rabbit brush-border membranes with chloroform/methanol and purified by hydroxyapatite chromatography. The protein has been incorporated by the dilution method into liposomes formed from different types and ratios of lipids. The greatest reconstitution has been achieved into liposomes prepared from cholesterol (20%), phosphatidylcholine (20%), phosphatidylethanolamine (30%) and phosphatidylserine (30%) (CH/PC/PE/PS). Pi uptake by these proteoliposomes had the following characteristics: (i) the initial rate was markedly greater in the presence of an inwardly directed Na+ gradient (600 pmol/10 s per mg) than with a K+ gradient (65 pmol/10 s per mg); (ii) maximal uptake was increased 8-fold above the equilibrium value ('overshoot') when a Na+ gradient was applied; (iii) Pi was not merely bound to proteoliposomes but was transported intravesicularly; and (iv) Na(+) dependent Pi uptake was sensitive to the known phosphate transport inhibitors. This first successful attempt of reconstitution of Na+/Pi transport activity into proteoliposomes led us to isolate and characterize physico-chemically the protein responsible. Its isoelectric point was about 5.8, and urea/SDS gel electrophoresis revealed a broad band of molecular mass ranging from 63 to 66 kDa under both reducing and non-reducing conditions. In the native form, the molecular mass analysed by gel filtration was estimated to be 170 +/- 10 kDa, suggesting that the protein is a polymer, probably stabilized by hydrophobic bonds. Endoglycosidase F treatment decreased the molecular mass to approx. 50 kDa. It is postulated that this acidic glycoprotein might represent a subunit of the intact Na+/Pi co-transporter from rabbit kidney brush-border membranes. PMID- 1520292 TI - Two gonadotropin-releasing hormones from African catfish (Clarias gariepinus). AB - Two forms of gonadotropin-releasing hormone (GnRH) have been purified from brain extracts of the African catfish, Clarias gariepinus, using reverse-phase high performance liquid chromatography (HPLC) and radioimmunoassay (RIA). The amino acid sequences of both forms of African catfish GnRH were determined using Edman degradation after digestion with pyroglutamyl aminopeptidase. In addition, both GnRHs were studied by mass spectrometry. The primary structure of African catfish GnRH I is identical to Thai catfish GnRH I, pGlu-His-Trp-Ser-His-Gly-Leu-Asn-Pro Gly-NH2, and the primary structure of African catfish GnRH II is identical to the widely distributed and highly conserved chicken GnRH II, pGlu-His-Trp-Ser-His-Gly Trp-Tyr-Pro-Gly-NH2. PMID- 1520293 TI - An apparently allosteric effect involving N2O with the nitrous oxide reductase from Wolinella succinogenes. AB - It was shown that kcat for the benzyl viologen cation (BV+)-N2O oxidoreductase activity of nitrous oxide reductase from Wolinella succinogenes was 2-3 times greater at high N2O concentrations than at low. This effect of N2O on kcat exhibited a titration curve implicating a single secondary binding site for N2O with a Kd of 130-200 microM (Km with respect to N2O is about 2.5 microM). This work represents the first evidence of an apparently allosteric kinetic effect among nitrous oxide reductases. Its possible cause is discussed. BV+ was generated in these kinetic studies by addition of sub-stoichiometric amounts of dithionite. This means of reduction proved to be superior to the photochemical generation of BV+ that had been used previously with the enzyme. Mass spectrometric measurements suggested that the M(r) of the subunit of the enzyme is about 95,500 rather than 88,000. PMID- 1520294 TI - Selective and potent inhibition of different hepatic UDP-glucuronosyltransferase activities by omega,omega,omega-triphenylalcohols and UDP derivatives. AB - A homologous series of omega,omega,omega-triphenylalcohols and corresponding omega,omega,omega-triphenylalkyl-UDP derivatives was synthesized and tested as inhibitors of UDP-glucuronosyltransferase (UGT) activity in rat liver microsomes, with 1-naphthol, testosterone and bilirubin as substrates. Introduction of the UDP moiety in the triphenylalcohols increased their inhibition potency markedly toward the isoforms which glucuronidate 1-naphthol and testosterone, but strongly decreased that toward bilirubin. The inhibiting potency of the UDP-derivatives increased as a function of the length of the hydrocarbon chain. The best inhibitor 7,7,7-triphenylheptyl-UDP showed an I50 of 30 and 10 microM for 1 naphthol and testosterone glucuronidation, respectively; even a 1 mM concentration of the compound had little, if any, effect on bilirubin glucuronidation. The inhibition by 7,7,7-triphenylheptyl-UDP was mixed-type toward 1-naphthol, and non competitive toward testosterone (apparent K(i) 30 microM and 1.7 microM, respectively); on the other hand, the inhibition was competitive toward the common substrate UDP-glucuronic acid (apparent K(i) 1.9 1.2 microM). In addition, 7,7,7-triphenylheptyl-UDP (0.25-0.50 mM) almost inhibited glucuronidation of 1-naphthol and testosterone catalyzed by the recombinant rat liver UGT-2B1 and human liver UGT-1A1, whose cDNA has been expressed in V79 cells. In conclusion, the data indicate that 7,7,7 triphenyheptyl-UDP interacted competitively with the UDP binding site of UGT. The results also indicate that it is possible to design transition state analogue inhibitors with specificity for different UGT forms. PMID- 1520295 TI - Crystallization and preliminary characterization of three crystal forms of human recombinant transforming growth factor-alpha. AB - Three crystal forms of human recombinant TGF-alpha have been grown from solutions containing 2-methyl-2,4-pentanediol. One of the forms belongs to the orthorhombic space group C222(1) and the other two belong to the monoclinic space group C2. Two of the crystal forms diffract to approximately 2.3 A Bragg spacings. X-ray diffraction data has been collected for all three forms. These data appear to be suitable for crystal structure determination, using either heavy atom isomorphous replacement methods or molecular replacement, for phase determination. PMID- 1520296 TI - The cloning and expression of a human alpha-1,3 fucosyltransferase capable of forming the E-selectin ligand. AB - The polymerase chain reaction was used to amplify a novel fucosyltransferase cDNA (FucT-VI) from A431 and from HL60 cells. The amplified cDNA has a high degree of sequence identity to FucT-V and to FucT-III, and a much lower level of similarity to FucT-IV. Transfection of the FucT-VI gene into mammalian cells confers alpha 1,3 fucosyltransferase activity to the cells, resulting in cell surface expression of Lewis x and sialyl-Lewis x carbohydrates. In contrast to FucT-IV activity, FucT-VI catalyzes the transfer of fucose from GDP-beta-fucose to alpha 2,3 sialylated substrates. The substrate specificity of the FucT-VI gene product suggests that FucT-VI may be an enzyme involved in the biosynthesis of the E Selectin ligand, sialyl-Lewis x, in myeloid cells. PMID- 1520297 TI - Enantioselectivity of the hydrolysis of linoleic acid monoepoxides catalyzed by soybean fatty acid epoxide hydrolase. AB - Soybean epoxide hydrolase efficiently catalyzes the hydration of the two positional isomers of linoleic acid monoepoxides into their corresponding vic diols. Kinetic analysis of the progress curves, obtained at low substrate concentrations (i.e. [So] much less than Km), and analysis of the residual substrates by chiral-phase HPLC, indicate that the hydrolase is highly enantioselective, i.e. cis-9R,10S-epoxy-12(Z)-octadecenoic and cis-12R,13S-epoxy 9(Z)-octadecenoic acids are preferentially hydrolyzed (the enantioselectivity ratios are 15 and 28, respectively). Importantly, these two enantiomers are the one formed preponderantly by epoxidation of linoleic acid by peroxygenase, a hydroperoxide-dependent oxidase we have previously described in soybean (Blee, E., and Schuber, F., Biochem. Biophys. Res. Commun. (1990) 173, 1354-1360). PMID- 1520298 TI - Purification of human placenta diamine oxidase. AB - Diamine oxidase (histaminase) is produced at very high levels by the decidual cells of the placenta. The presence of diamine oxidase has been demonstrated in human neutrophils. Purification of human placenta diamine oxidase was performed by four subfractionation steps and led to the isolation of one polypeptide whose molecular weight was 84,000, as assessed by SDS PAGE. Using polyclonal antibodies raised against the purified enzyme, we have demonstrated that the neutrophil diamine oxidase is immunochemically identical to the placental diamine oxidase. Development of immunological methods will be useful for detection and quantitation of diamine oxidase in neutrophils during the inflammation process. PMID- 1520299 TI - Effect of semi-random mutagenesis at the C-terminal 4 amino acids of human interleukin-6 on its biological activity. AB - The carboxyl(C)-terminus of human interleukin-6 (hIL-6) has a critical role in the expression of the biological activity of this cytokine. To define the structure-function relationships of this region, semi-random mutagenesis of the C terminal Leu181-Arg182-Qln183-Met184 sequence of hIL-6 was performed. The mutants were produced in Escherichia coli, renatured, and purified. Alterations of the C terminal 4 amino acids caused a significant reduction of the proliferative effect of the mutants on MH60.BSF2 and KT-3 cells, and also led to a drastic decrease in receptor binding affinity. These results suggest the importance of a positively charged residue at position 182 or 183 and an alpha-helix at position 181 for the biological activity of hIL-6. PMID- 1520301 TI - Changes in bioactive lipids, alkylacylglycerol and ceramide, occur in HIV infected cells. AB - The mass levels of bioactive lipids known to modulate signal transduction or to possess other biological activities were measured in HIV-infected CEM cells. The levels of diacylglycerol, an activator of protein kinase C, as well as of alkylacylglycerol were elevated. A more drastic increase was observed in the ceramide levels after HIV-infection, whereas sphingosine levels were hardly influenced. Interestingly, the magnitude of the changes was related to the infection time, being higher at 8 days after infection then at 4 days. The possible role of these lipids in the cytopathic effects of HIV-infection is discussed. In addition, an improved methodology to quantitate simultaneously diacylglycerol and alkylacylglycerol in crude lipid extracts, based upon their phosphorylation by E. coli diacylglycerol kinase, is presented. PMID- 1520300 TI - Effects of osmotic stress and hyperglycemia on aldose reductase gene expression in human renal proximal tubule cells. AB - Sorbitol levels in proximal tubule cells cultured for 96 h in the presence of 16.5 mM and 27.5 mM glucose were significantly elevated when compared to cells cultured in 5.5 mM glucose. No changes in the levels of aldose reductase activity, mRNA and immunoreactivity were observed in cells cultured for up to 168 h in media containing either 5.5 mM or 27.5 mM glucose. In contrast, cells cultured in the presence of hypertonic media (600 mosmol/kg) containing either 5.5 mM or 27.5 mM glucose contained markedly elevated aldose reductase activity, mRNA and immunoreactivity. These results demonstrate that exposure of human renal proximal tubule cells to elevated glucose for up to 168 h does not result in enhancement of aldose reductase gene expression at transcriptional, translational or post-translational levels. However, exposure to a hyperosmotic milieu causes dramatic induction of aldose reductase gene expression. PMID- 1520302 TI - Cancer-associated glycoproteins defined by a monoclonal antibody, MLS 128, recognizing the Tn antigen. AB - A murine monoclonal antibody, MLS 128, recognizing the Tn antigen, was established and used for characterization of glycoproteins expressing the Tn antigen. The Tn antigen was expressed on three polypeptide chains with molecular weights of 250k, 210k and 150k daltons. LS 180 cells were labeled with 3H glucosamine or 35S-sulfate metabolically, and then the immunoprecipitate derived from the cell lysate was subjected to SDS-PAGE followed by fluorography. It was revealed that these Tn antigen glycoproteins were produced through the processing of a high molecular weight precursor. The carbohydrate moieties of the Tn antigen glycoproteins labeled with 3H-glucosamine were released with alkaline borohydride, and the released sugars were examined by gel filtration and paper chromatography. The carbohydrates predominantly consisted of GalNAc and sialyl GalNAc (greater than 90%), with a nearly equal distribution. PMID- 1520303 TI - TGF beta inhibits rat thyroid cell proliferation without alterations in the expression of TSH-induced cell cycle-related genes. AB - Transforming growth factor beta (TGF beta) is a secreted polypeptide factor that is thought to play a major role in the regulation of proliferation of many cell types and various differentiation processes. TGF beta acts on thyroid cells by inhibiting cell proliferation and expression of differentiation markers, such as thyroglobulin production and iodide uptake. Exponentially growing thyroid cells cultures accumulate mostly in G0/G1 after exposure to TGF beta for 48 hours. TGF beta inhibits the TSH induced transition of quiescent thyroid cell from the G0 to the S phase. These effects on the thyroid cell growth, however, are not mediated by changes in the TSH-induced cell cycle-related genes expression; both immediate early and progression genes expression is unaffected by the TGF beta treatment. PMID- 1520304 TI - Retinoic acid ambivalently regulates the expression of MyoD1 in the myogenic cells in the limb buds of the early developmental stages. AB - The expression of MyoD1 in myogenic cells located in the muscle prospective region of the limb bud at stage 20-22 was highly sensitive to retinoic acid. Unlike RAR-beta, the expression of MyoD1 mRNA in the muscle precursor cells was significantly increased by retinoic acid at lower concentrations (0.1-10 nM), but inhibited by it at higher concentrations (0.1-1 microM). The ambivalent modulation of MyoD1 expression suggested that MyoD1 expression is regulated by not only the retinoic acid receptor and its response element, but also by other factors. Retinoic acid may be involved in the differentiation of the myogenic cells during early development. PMID- 1520305 TI - PCR derived cDNA clones for X-linked phosphoglycerate kinase-1 in a marsupial, the tammar wallaby (Macropus eugenii). AB - cDNA clones for the X-linked PGK-1 were obtained from a tammar wallaby liver by PCR and sequenced. The PGK-1 gene published here is the consensus sequence of those clones. The sequence represents an open reading frame of 1251 bp. Sequence comparisons to X-linked and autosomal sequences showed the greatest homology with the X-linked PGK-1 genes in eutherian species. This sequence opens the way for studying the paternal X inactivation phenomenon in marsupials and will assist in defining the time course of mammalian evolution. PMID- 1520306 TI - Photo-induced crosslinking of histones H3 and H1 to DNA in deoxyribonucleoprotein: implication in studying histone-DNA interactions. AB - A thymine-modified derivative of histone H3, isolated as a result of heat treatment of covalently crosslinked DNA-protein photoadduct from UV-irradiated chromatin, was obtained. Sequence analysis of one of its tryptic peptides revealed that lysine-14 of the N-terminal tail of the histone H3 molecule covalently binds to thymine residue of DNA. This type of UV-crosslinking is most probably the only type for histone H3 and, possibly, for H1. PMID- 1520307 TI - Pretreatment effects of jelly components on the sperm acrosome reaction and histone degradation in the starfish, Asterina pectinifera. AB - Acrosome reaction (AR) and histone degradation (HD) of Asterina pectinifera sperm are induced by co-operation of ARIS and a diffusible fraction (M8) of egg jelly. Once sperm are treated with ARIS or M8 separately for several minutes, they do not undergo the AR in response to the egg jelly. Preincubation of sperm with M8 at 0 degrees C is not effective to block the jelly-induced AR whereas inhibitory effects of ARIS remain at 0 degrees C. Jelly-induced HD is inhibited by pretreatment of sperm with ARIS but is not affected by the incubation with M8. The blockage of the jelly-induced reactions, both AR and HD, by ARIS- or M8 pretreatment can be bypassed by ionophores, A23187 and monensin. PMID- 1520308 TI - Egg jelly components responsible for histone degradation and acrosome reaction in the starfish, Asterina pectinifera. AB - In the starfish, Asterina pectinifera, egg jelly induces the degradation of sperm histones as well as the acrosome reaction. We have isolated histone degradation inducing components from the egg jelly. The histone degradation and the acrosome reaction are induced by a co-operative action of ARIS, which is an extremely large, sulfated glycoprotein with diffusible substance(s) in the jelly. Co-ARIS I, a steroidal saponin of the jelly, is effective to induce both reactions in the presence of ARIS. PMID- 1520309 TI - Human platelet factor 4 is a direct inhibitor of human osteoblast-like osteosarcoma cell growth. AB - The effect of purified human platelet factor 4, a platelet alpha-granule protein, on the growth of the human osteoblastic osteosarcoma cell lines Saos-2 and G-292 was investigated. Platelet factor 4 (20 ng/ml to 2 micrograms/ml) caused a significant, dose-dependent inhibition of human osteoblast-like osteosarcoma cell proliferation. Platelet factor 4 exerted its inhibitory effect under all growth conditions tested: serum-free, serum-stimulated and thrombin-stimulated. The platelet factor 4-induced cell inhibition was not associated with a cytotoxic effect on the cells (assessed by lactate dehydrogenase release). The inhibitory effect of platelet factor 4 was not affected by the presence of indomethacin in the cultures, indicating that the effect was prostaglandin-independent. These results suggest that platelet factor 4 has direct antitumor effects and that it may be important in pathological and physiological processes of bone. PMID- 1520310 TI - Demonstration of antigenic similarities and variations in excretory/secretory antigens of Toxoplasma gondii. AB - C57BL/6 mice were orally infected with different doses of cysts of ME49 strain of Toxoplasma gondii to produce groups of acutely and chronically infected mice. Sera were obtained at different periods post-infection. SDS-PAGE was ran with excretory/secretory antigens of ME49 and RH strains of T. gondii, followed by Western blot analyses using the above sera and anti- IgA, IgM, IgG as conjugates. The SDS-PAGE profiles of the two antigens were similar. However the antigenic bands showed variations in all blots, most evidently in IgA blots of chronic sera. IgG blots showed greatest similarities in reactive bands. In IgM blots, more common bands were shown in chronic sera than in acute sera. Variations and similarities in prominence of some bands and time of their appearance were also noted, especially in IgM and IgG blots of chronic sera. Thus antigenic variations and similarities are present in excretory/secretory products of different strains of T. gondii. PMID- 1520311 TI - Expression of two S-ribonucleases of Petunia inflata using baculovirus expression system. AB - We have previously shown that three Petunia inflata S-proteins, products of the multiallelic S-gene of the self-incompatibility system, are ribonucleases. Here we report the expression of cDNAs for two of these S-proteins using the baculovirus expression system. S2- and S3-proteins were found in both supernatants and lysates of Spodoptera frugiperda cells infected with recombinant baculoviruses. Both recombinant S-proteins contained glycosylated (25 kD) and nonglycosylated (23 kD) forms. Recombinant S2- and S3-proteins were purified from insect cell cultures, and the amino-terminal sequences determined from glycosylated S2- and S3-proteins indicated that the leader peptide encoded by each cDNA was correctly removed. Both glycosylated and nonglycosylated forms of S2- and S3-proteins exhibited ribonuclease activity. PMID- 1520312 TI - Effect of 5-fluorouracil on interleukin-2 expression. AB - The effect of 5-fluorouracil on the expression of IL-2 gene and the production of IL-2 protein has been studied using spleenic lymphocytes of rats. The IL-2 messenger RNA has been quantitated by dot-blots and IL-2 has been assayed by Con A-blast assay. The results show that there is up to 3.75 fold increase in the production of IL-2 message in 5-fluorouracil treated lymphocytes over Con A treated controls. There is also a concomitant increase in IL-2 protein production upon 5-fluorouracil treatment in rat lymphocytes. PMID- 1520313 TI - Reconstitution of cytochrome P4502B4 (LM2) activity with camphor and linalool monooxygenase electron donors. AB - The P4502B4 (LM2) monooxygenase was shown to bind the P450cam and P450lin redoxins with respective dissociation constants of ca. 500 and 100 microM. When the redoxin reductases are added, the heterogeneous complexes demethylate benzphetamine with HCHO yields and Vmax similar to results with the homologous microsomal reductase. Implications of evolutionary conserved P450 redox electron donor binding site residues are discussed. PMID- 1520314 TI - Identification of novel RNA-binding proteins that interact in the coding region of protein D sense RNA in vitro. AB - Ultraviolet (UV)-cross-linking and sodium dodecyl sulfate(SDS) polyacrylamide gel electrophoretic (PAGE) analysis were used to identify proteins of nuclear and cytosolic (S100) origin that specifically bind to an in vitro transcribed mRNA sequence for protein D. The coding region of the protein D cDNA was subcloned, in vitro transcribed to [32P]RNA, and incubated with nuclear and cytosolic extracts of enzymatically dispersed epididymal cells. As revealed by UV-cross-linking and SDS-PAGE analysis, two proteins exhibiting a molecular weight mass of approximately 2.5 and approximately 35 Kd that specifically recognize and bind to the in vitro transcribed mRNA sequence for protein D. Our findings suggest that the regulation of protein D gene expression in the rat epididymis may involve novel RNA-binding proteins. PMID- 1520315 TI - Affinity labeling of vertebrate oxidosqualene cyclases with a tritiated suicide substrate. AB - Pig and rat liver oxidosqualene cyclase (OSC) enzymes were purified to homogeneity and showed single bands on SDS-polyacrylamide gel electrophoresis with molecular masses of 75 kDa (pig) and 78 kDa (rat). Pig liver OSC was purified for the first time (441-fold with a yield of 39%). Chemical affinity labeling of pure or crude preparations of the liver cyclases using the mechanism based irreversible inhibitor of OSC, [3H]29-methylidene-2,3-oxidosqualene ([3H]29 MOS), showed a single radioactive band at 75 kDa (pig) and 78 kDa (rat). Affinity labeling experiments were also performed with dog and human microsomal preparations and with yeast and plant cyclases. All of the vertebrate OSC enzymes were specifically labeled with [3H]29-MOS and gave a single band with molecular masses ranging from 70 to 80 kDa (rat, 78 kDa; dog, 73 kDa; pig, 75 kDa; and human, 73 kDa). In contrast, yeast lanosterol cyclase and plant cycloartenol cyclase were not labeled, demonstrating subtle differences in the active sites of animal, plant, and fungal enzymes. PMID- 1520316 TI - Conformational feature of neuroactive domoic acid: X-ray structural comparison with isodomoic acid A and alpha-kainic acid. AB - As an aid for developing a new type of potent insecticide acting on the neuromuscular junction, conformational characteristics of domoic acid and isodomoic acid A, the naturally occurring glutamate agonists, were investigated by X-ray crystal analyses. Conformational comparison with a neuroactive alpha kainic acid provides information concerning the stereochemical feature responsible for the biological activity. PMID- 1520317 TI - Expression of two types of neurofibromatosis type 1 gene transcripts in gastric cancers and comparison of GAP activities. AB - To understand the molecular mechanism of gastric tumorigenesis, the status of neurofibromatosis type 1 (NF1) gene was analyzed in human gastric cancer cell lines. Although the sequencing of the GTPase activating protein (GAP)-related region of NF1 (NF1-GRD) revealed no apparent mutation, the NF1-GRD transcript (type I) and that containing an additional 63 bp insert in the center of NF1-GRD (type II) were equally expressed in most gastric cancer cells. By contrast, type II was predominantly expressed in normal stomach mucosa. When these two types of NF1-GRD were bacterially expressed and their GAP activities were tested, both types of NF1-GRD similarly stimulated ras GTPase activity. However, arachidonic acid inhibited GAP activities of two types of NF1-GRD to different extents. These results suggest that the increased expression of type I NF1 protein may modulate ras-related signal transduction and it may be related to the control of the gastric cellular proliferation. PMID- 1520318 TI - Metabolic studies in a mouse model of hepatorenal tyrosinemia: absence of perinatal abnormalities. AB - Radiation induced chromosomal deletions at the albino locus in the mouse, lethal when homozygous, cause abnormalities of expression of several unlinked liver specific genes. Recently, the gene encoding FAH was shown to be included in the deletions. Since in humans FAH mutations cause tyrosinemia type I, deletion homozygous mice were suspected of having tyrosinemia. Studies of plasma amino acids did not confirm this suspicion. Also, succinylacetone levels were normal in fetal and newborn livers of deletion homozygotes. The present evidence, therefore, does not support the assumption that the earlier described ultrastructural and enzyme abnormalities in deletion homozygotes are secondary effects of tyrosinemia caused by the deletion of FAH. PMID- 1520319 TI - Specific erythroid differentiation of mouse erythroleukemia cells by activins and its enhancement by retinoic acids. AB - Activin A has been shown to induce hemoglobin production in various hematopoietic cells. Such activities of three structurally distinct activins (activin A, activin AB, and activin B) were compared using F5-5 mouse erythroleukemia cells. Activin A and AB had similarly potent inducing activities whereas that of activin B was much lower. The erythroid inducing activity of activins was suppressed by follistatin, an activin-binding protein but not by inhibin A and inhibin B. Retinoic acids (both all-trans and 13-cis) had weak erythroid differentiation activity. In addition, clear synergistic erythroid induction occurred when retinoic acid and activin A were mixed together. These results indicate that retinoic acid may modulate activin-induced erythropoiesis in vivo. PMID- 1520320 TI - Acyl-trafficking in membrane phospholipid fatty acid turnover: the transfer of fatty acid from the acyl-L-carnitine pool to membrane phospholipids in intact human erythrocytes. AB - In this work we have investigated the transfer of radioactive palmitic acid between membrane phospholipids and acyl-L-carnitines in intact human erythrocytes. During the incubation period of labeled erythrocyte in non-defatted bovine serum albumin, radioactivity in phosphatidylcholine and phosphatidylethanolamine increased. On the contrary, a decrease of radioactivity in erythrocyte palmitoyl-L-carnitine was observed. 2-Tetradecylglycidic acid, an irreversible erythrocyte carnitine palmitoyltransferase inhibitor, abolished any radioactivity changes in both phospholipids and palmitoyl-L-carnitine. Similar findings were obtained by using erythrocytes labeled with radioactive oleic acid. Our data suggest that in human erythrocytes a carnitine palmitoyltransferase catalyzed acyl transfer from acyl-L-carnitine to phospholipids, rather than a previously described fatty acid transfer from phosphatidylcholine to phosphatidylethanolamine, is operative. PMID- 1520321 TI - Multiple mRNA forms of human GTP cyclohydrolase I. AB - To isolate full length cDNA clones encoding human GTP cyclohydrolase I, the first and rate-limiting enzyme in tetrahydrobiopterin biosynthesis, a cDNA library generated from human liver was screened by plaque hybridization. Analysis of the clones, hybridized with rat cDNA fragment, by restriction mapping and partial sequencing showed the existence of three kinds of cDNAs. All three cDNAs were identical in their central and 5' regions. They were, however, found to diverge at 3' ends. Furthermore, the three species of mRNAs corresponding to the three cDNAs were detected in human liver by reverse transcription-polymerase chain reaction (RT-PCR) analysis. These results indicate that, in humans, GTP cyclohydrolase I molecules are encoded by at least three distinct mRNAs. PMID- 1520322 TI - Human histo-blood group A2 transferase coded by A2 allele, one of the A subtypes, is characterized by a single base deletion in the coding sequence, which results in an additional domain at the carboxyl terminal. AB - We have identified a possible mutation which characterizes A2 alleles (a minor subtype of A) at the human histo-blood group ABO locus based on polymerase chain reaction (PCR) of genomic DNA, followed by nucleotide sequencing of the amplified fragments. The A2 subtype has a single base deletion near the carboxyl terminal. As a result of frame-shifting, A2 transferase possesses an extra domain. Introduction of this single base deletion into the A1 transferase cDNA expression construct drastically decreased the A transferase activity in DNA-transfected HeLa cells. PMID- 1520323 TI - Molecular cloning of nucleobindin, a novel DNA-binding protein that contains both a signal peptide and a leucine zipper structure. AB - We have previously reported that KML1-7 cells cloned from a lupus-prone MRL/l mouse produced a soluble factor that preferentially expanded anti-DNA antibody production across the H-2 barrier. We purified this factor, a 55 kD protein that we termed nucleobindin (Nuc), and obtained its cDNA clone. Although the gene for Nuc encodes a signal peptide and, in fact, Nuc was identified as a secreted protein, Nuc had a DNA-binding property. The putative polypeptide predicted from the cDNA sequence featured a signal peptide, a leucine zipper structure and a basic amino acid-rich region. The DNA-binding property of Nuc was destroyed by deletion of either the leucine zipper structure or the basic amino acid-rich region. The amino acid sequences of Nuc are highly conserved between mouse and human. We discuss the possible role of Nuc in autoimmunity. PMID- 1520324 TI - Characterization of a protease with alpha- and beta-fibrinogenase activity from the Western diamondback rattlesnake, Crotalus atrox. AB - A metalloprotease from the rattlesnake Crotalus atrox venom was isolated and purified from multiple-step chromatographies including anion-exchange chromatography, gel permeation and reversed-phase HPLC. The fraction was shown to be homogeneous as judged by SDS-gel electrophoresis. It also showed a high proteolytic activity against alpha- and beta-chains of fibrinogen molecules. Further characterization of the purified fraction with fibrinogenase activity indicated that it is a single-chain protease with a molecular mass of about 24 kDa and an acidic isoelectric point. It is relatively heat stable up to about 65 degrees C, inhibited by EDTA, beta-mercaptoethanol, but not by phenylmethanesulfonyl fluoride, N alpha-p-tosyl-L-phenylalanine chloromethyl ketone and N alpha-p-tosyl-L-lysine chloromethyl ketone, soybean trypsin inhibitor and aprotinin. Amino acid analysis showed that the enzyme possesses an amino acid composition very similar to some metalloproteases characterized before from the closely related rattlesnake venoms. N-Terminal sequence analysis of the enzyme corroborated some similarity between this enzyme and the reported sequences of these enzymes characterized from the Crotalidae snake family. This study indicated the presence of a novel fibrinogenase (termed Catroxase) with N terminal sequence different from the metalloprotease with hemorrhagic activity isolated from the same Western diamondback rattlesnake. PMID- 1520325 TI - On the stability of bovine gamma II crystallin. AB - Bovine gamma II crystallin, undergoes structural changes when lyophilized. The lyophylized powder does not readily dissolve in buffer, although it can be taken up in distilled water. The lyophylized sample, as opposed to a sample concentrated by vacuum distillation at 30 degrees C, does exhibit different migration on isoelectric focusing gels. The hydration and denaturation properties of the two preparations are different. The lyophylized sample possesses a higher non-freezable water content as a function of concentration than its counterpart. The lyophylized sample also shows less denaturation in differential scanning calorimetry scans, up to 110 degrees C, than its counterpart. This indicates that lyophylization may induce a slight denaturation, due to structural-conformational change. On the other hand, the CD spectra of lyophylized and non-lyophylized gamma II crystallins do not differ significantly. This implies that the conformational changes upon lyophylization do not involve the secondary structure of gamma II crystallin. PMID- 1520326 TI - A novel transthyretin mutation at position 30 (Leu for Val) associated with familial amyloidotic polyneuropathy. AB - A novel transthyretin (TTR) mutation associated with familial amyloidotic polyneuropathy was detected in a Japanese patient. Single-strand conformation polymorphism analysis and sequence analysis of polymerase chain reaction (PCR) amplified exons of the patient's TTR gene revealed a point mutation resulting in a substitution of leucine for valine at position 30. As the mutation creates a Cfr13I site, it was confirmed by PCR and restriction analysis. Our finding indicates the importance of position 30 in TTR-derived amyloid fibril formation. PMID- 1520327 TI - Production and properties of novel human thyroid cancer specific monoclonal antibodies. AB - Monoclonal antibodies (TCM-7, -9 and -12) against human thyroid differentiated cancers were established by screening with human thyroid cancers, normal and benign thyroid tissue, and normal human serum protein. A monoclonal antibody (TCM 9) with strong specificity for human thyroid cancer but not for Graves' disease, adenoma or normal thyroid, was shown to recognize a 300 K protein but not to bind to native or mature human thyroglobulin. When TCM-9 was used in immunohistochemical staining tests on more than 30 types of non-thyroid lesions, no reactivity of TCM-9 was observed except with skin immature teratoma, lip squamous carcinoma and stomach adenocarcinoma, which revealed weak reactivities. TCM-9 also showed strong reactivity with two undifferentiated thyroid cancer cell lines and one tissue specimen. Thus TCM-9 is a novel monoclonal antibody against the thyroid cancer. PMID- 1520328 TI - Negative regulation of the murine cytosolic aldehyde dehydrogenase-3 (Aldh-3c) gene by functional CYP1A1 and CYP1A2 proteins. AB - We have examined enzyme activities and mRNA levels corresponding to aldehyde dehydrogenase-3 genes encoding cytosolic (ALDH3c) and microsomal (ALDH3m) forms. In contrast to negligible activities in the intact mouse liver, both ALDH3c and ALDH3m enzyme activities are inducible by benzo[a]pyrene and 2,3,7,8 tetrachlorodibenzo-p-dioxin (TCDD) in mouse hepatoma Hepa-1c1c7 cell cultures. Constitutive mRNA levels of ALDH3c are virtually absent, whereas those of ALDH3m are substantial; using Hepa-1 mutant lines, we show that both ALDH3c and ALDH3m are TCDD-inducible by an Ah receptor-dependent mechanism. Basal mRNA levels of ALDH3c, but not those of ALDH3m, are strikingly elevated in untreated mutant cells lacking a functional CYP1A1 enzyme; low ALDH3c basal mRNA levels can be restored by introduction of a functional murine CYP1A1 or human CYP1A2 enzyme into these mutant cells. These data suggest that the TCDD induction process is distinct from the CYP1A1/CYP1A2 metabolism-dependent repression of constitutive gene expression; we suggest that this latter property classifies the Aldh-3c gene, but not the Aldh-3m gene, as a member of the murine [Ah] battery. PMID- 1520329 TI - Polymerase chain reaction--amplification of the coding sequence of the type X collagen gene from genomic DNA and identification of a polymorphism that changes Gly to Arg at position 545 by single-strand conformation polymorphism analysis. AB - Type X collagen is a specific product of hypertrophic growth plate chondrocytes and it has been suggested that mutations in the corresponding gene (COL1OA1) may be responsible for certain heritable disorders affecting growth plate cartilage such as the epiphyseal dysplasias. We have amplified the coding region of COL1OA1 employing polymerase chain reaction (PCR) of genomic DNA. Single-strand conformation polymorphism (SSCP) analysis of PCR products followed by direct sequencing identified a G to C transition that results in a Gly to Arg substitution at position 545 of the polypeptide chain. The sequence variation was confirmed by restriction enzyme analysis with BsaJ 1. Analysis of a family with multiple epiphyseal dysplasia ruled out this sequence change as a cause of the disease. This is the first report showing application of SSCP for detection of a sequence variant in COL1OA1. PMID- 1520330 TI - Site directed mutagenesis of two cysteine residues in the E. coli ogt O6 alkylguanine DNA alkyltransferase protein. AB - The E. coli ogt O6-alkylguanine-DNA alkyltransferase has two cysteine residues positioned identically with respect to cysteines in the E. coli ada O6 alkylguanine-DNA alkyltransferase. In order to assess their function, these residues were each substituted by a glycine to generate altered forms of the ogt protein. Mutagenesis of cysteine-139, located within a 'PCHRV' region of homology, eliminated functional activity confirming that this residue is the methyl-accepting cysteine in the active site of the protein. Substitution of cysteine 102 within the sequence 'LRTIPCG' had little effect on the ogt protein activity demonstrating that this cysteine is not directly involved with the transfer of O6-methylguanine adducts. PMID- 1520331 TI - 8-Azidoadenosine and ribonucleotide reductase. AB - Inhibitors of ribonucleotide reductase are potential antiproliferative agents, since they deplete cells from DNA precursors. Substrate nucleoside analogues, carrying azido groups at the base moiety, are shown to have strong cytostatic properties, as measured by the inhibition of the incorporation of thymidine into DNA. One compound, 8-azidoadenosine, inhibits CDP reduction in cytosolic extracts from cancer cells. The corresponding diphosphate behaves as a substrate for ribonucleotide reductase while the triphosphate is an allosteric effector. PMID- 1520332 TI - Recovery of ornithine decarboxylase activity after inhibition with alpha difluoromethylornithine. AB - alpha-Difluoromethylornithine is an effective inhibitor of polyamine biosynthesis because of its specificity for ornithine decarboxylase and the fact that its attachment to this enzyme is considered to be irreversible. We have found, however, that ornithine decarboxylase inactivated with this inhibitor in intact cells, as well as purified enzyme inactivated in vitro, both are capable of releasing this inhibitor and recovering enzyme activity. This reactivation can be initiated by freezing of inactivated enzyme samples in the presence of reducing agents at -7 or -20 degrees C and can be partially induced at 37 degrees C. These results reveal an unexpected lability of this enzyme-inhibitor complex that needs to be considered in future experimental designs. PMID- 1520333 TI - Molecular cloning of the alcohol/hydroxysteroid form (hSTa) of sulfotransferase from human liver. AB - A cDNA encoding the human alcohol/hydroxysteroid sulfotransferase (h-ST-a), which catalyzes the sulfo-conjugation of many drugs and hormones, was isolated from a human liver cDNA library using a rat STa (rSTa) cDNA probe. The cDNA, designated as hSTa, consists of 1069 base pairs (bp) and contains an 855-nucleotide open reading frame beginning at nucleotide 65, which encodes a 285 amino acid polypeptide of 33.76 kDa. A second cDNA clone (1563 bp) was truncated 5' at nucleotide 231 (lacking the first 15 amino acids) with identical coding region, however, it had a much longer 3' untranslated region (UTR). Both clones contained a short segment of poly(A)+ tail. Northern blot analysis of an adult human liver showed that there are at least 2 mature mRNA with sizes ranging from approximately 1.1 kb to 1.7 kb, verifying the authenticity of the obtained cDNA clones. From the sequence alignment, the hSTa shares 62%/74%, 39%/59%, 35%/48%, 36%/54% identity with rSTa, rSTp (phenol), rSTe (estrogen), and bovine STe (bSTe) at the deduced amino acid and DNA levels, respectively, indicating that there are at least three subfamilies (alcohol, phenol and estrogen) of genes that encode for sulfotransferases in mammals. PMID- 1520334 TI - Direct demonstration of transcriptional activation of collagen gene expression in systemic sclerosis fibroblasts: insensitivity to TGF beta 1 stimulation. AB - Lesional fibroblasts propagated from the skin of patients with scleroderma, when compared to normal fibroblasts, show increased synthesis of several collagens and increased levels of their corresponding mRNAs. Using constructs (COL1A2/CAT) containing the promoter for the alpha 2 (I) collagen gene in transient transfection assays with matched pairs of scleroderma and normal skin fibroblasts, we observed higher transcriptional activity of the COL1A2 gene in scleroderma fibroblasts and, in contrast to normal fibroblasts, no further expression was observed in the presence of TGF beta 1. Analysis of the expression of COL1A2 promoter deletion constructs indicates that the TGF beta responsive element functional in normal fibroblasts and the sequence involved in intrinsic upregulation of COL1A2 gene expression in scleroderma fibroblasts are both located between bp-376 (Bgl II) and bp-108 (Sma I) sites. These data may indicate that intrinsic upregulation of extracellular matrix genes in scleroderma fibroblasts utilizes a TGF beta dependent pathway. PMID- 1520335 TI - 12(R)-hydroxyeicosatetraenoic acid synthesis by 3-methylcholanthrene- and clofibrate-inducible cytochrome P450 in porcine ciliary epithelium. AB - Porcine ciliary epithelial microsomes synthesized 12[S]-hydroxy-5, 8, 10, 14 eicosatetraenoic acid (12[S]-HETE) from arachidonic acid by a membrane-bound lipoxygenase and 12[R]-isomer by the cytochrome P450-dependent monooxygenase system. The activity to form 12(R)-isomer was markedly enhanced by 3 methylcholanthrene and clofibrate. Both basal and induced levels of 12(R)-HETE synthesizing activity were considerably higher in nonpigmented epithelial cells than in pigmented cells of the ciliary processes. The induced activity was suppressed by polyclonal antibodies raised against purified cytochrome P450 IA1 and NADPH-P450 reductase but not by substrates for clofibrate-inducible omega/omega-1 hydroxylases (P450 IVA-mediated). These results suggest that 12(R) HETE synthesis by porcine ciliary microsomes may be mediated by a cytochrome P450 of the IA family. PMID- 1520336 TI - Novel variant transthyretin gene (Ser50 to Ile) in familial cardiac amyloidosis. AB - We detected a point mutation in the transthyretin (TTR) gene in a patient with familial cardiac amyloidosis by using PCR-DCP (DNA conformation polymorphism) analysis that is based on the diversity in electrophoretic mobility of single stranded DNAs and/or heteroduplex DNAs in PCR products. The PCR products of the transthyretin gene were denatured in the presence of formamide and electrophoresed in a non-denaturing polyacrylamide gel to detect an electrophoretic change due to a sequence variation. An unusual DNA fragment was visualized by silver staining in the PCR products of the exon 3 from the patient. Subsequent sequencing analysis revealed a T to A transversion and led to a replacement of Ser by Ile at codon 50 of the TTR gene. PMID- 1520337 TI - cDNA cloning of the neutrophil bactericidal peptide indolicidin. AB - A structurally novel, tryptophan-rich antimicrobial tridecapeptide amide, named indolicidin, has recently been purified from bovine neutrophils (Selsted et al. (1992) J. Biol. Chem. 267, 4292-4295). Here we describe the molecular cloning of this endoantibiotic, which is synthesised in bone marrow cells as a 144 amino acid residue precursor. The encoded protein has a predicted mass of 16479 Da and a pI of 6.51. A putative signal peptide of 29 amino acids precedes a 101 residue pro-region. The mature peptide is at the 3' end of the open reading frame. A glycine, not found in purified indolicidin, is present at the carboxyl terminus of the deduced sequence and is very likely involved in post-translational peptide amidation. PMID- 1520338 TI - Isolation and characterization of a 25 kDa antifungal protein from flax seeds. AB - We have purified a 25 kDa protein from flax seeds to homogeneity by polyethyleneimine precipitation, ammonium sulfate precipitation, chitin extraction, Mono S cation exchange and C18 reversed phase column chromatographies. The purified protein strongly inhibited the growth of the agronomically important pathogen Alternaria solani, the causative agent of tomato early blight and in synergy with nikkomycin Z strongly inhibited the human pathogen Candida albicans. Amino terminal sequence analysis of the purified protein indicated that it has a high degree of homology to other reported pathogenesis-related antifungal proteins. PMID- 1520339 TI - Enhanced papilloma formation in response to skin tumor promotion in transgenic mice overexpressing the human ornithine decarboxylase gene. AB - We have studied the induction of papilloma formation in response to skin tumor promotion in transgenic mice overexpressing the human ornithine decarboxylase gene and in their nontransgenic littermates. The transgenic animals displayed a basal epidermal ornithine decarboxylase activity that was nearly 20 times higher than in their nontransgenic littermates. A single topical application of 12-O tetradecanoylphorbol-13-acetate induced a much more profound and longer-lasting increase in transgene-derived ornithine decarboxylase activity in comparison with the endogenous enzyme activity. Initiation of skin tumorigenesis with a single topical application of dimethylbenz[a]antracene followed by twice-weekly application of 12-O-tetradecanoylphorbol-13-acetate resulted in the appearance of first papillomas both in nontransgenic and transgenic animals by week 7. However, after 11 weeks of 12-O-tetradecanoylphorbol-13-acetate application, the number of papillomas per animal was almost 100% higher in the transgenic animals than in their nontransgenic littermates. These results indicate that an overexpression of epidermal ornithine decarboxylase confers a growth advantage on skin tumors in vivo. PMID- 1520340 TI - Complex role of protein kinase C in mediating the supramaximal inhibition of pancreatic secretion observed with cholecystokinin. AB - Protein kinase C appears to play an important, yet complex role in the supramaximal inhibition of pancreatic acinar cell secretion observed in response to cholecystokinin (CCK). The addition of protein kinase C activation to the concentration-response curve of a partial agonist acting at the CCK receptor (a phenethyl ester analogue of CCK), transforms a curve without supramaximal inhibition to a full agonist curve typical of CCK. This effect can be elicited by low concentrations of phorbol ester (50pM to 1nM 12-0-tetradecanoyl-phorbol-13 acetate) or by hormonal agonists (0.1 microM carbamylcholine, 10pM bombesin, 1pM CCK-8) which activate protein kinase C, but not by agonists acting via alternate second messengers (VIP). Of interest, this effect is dependent on preincubation of the acinar cells with the protein kinase C activator at 37 degrees C, with the effect rapidly reversed by transient exposure of the cells to lower temperature. This is consistent with mediation by a phosphorylation event. However, the requirement for an extended (greater than 15 min) preincubation period when using minimal kinase activation suggests that this phenomenon is more complicated than a simple bimolecular phosphorylation event and likely includes a series of events such as translocation of substrates and/or enzymes involved. PMID- 1520341 TI - Okadaic acid is a potent inducer of AP-1, NF-kappa B, and tumor necrosis factor alpha in human B lymphocytes. AB - Treatment of human B lymphocytes with an optimal concentration of okadaic acid, an inhibitor of phosphatases 1 and 2A, resulted in the induction of the transcription factor, AP-1 and a marked increase in NF-kappa B levels. In contrast, no effect on the levels of the octamer binding proteins, Oct-1 or Oct 2, were found. Since both AP-1 and NF-kappa B have been reported to be important in the induction of the tumor necrosis factor-alpha (TNF-alpha) gene we examined the effects of okadaic acid on TNF-alpha mRNA levels. Treatment with okadaic acid resulted in a striking increase in TNF-alpha mRNA transcripts within 1 h of stimulation and large amounts of TNF-alpha were released into the culture media. Although okadaic acid provides a potent inductive signal for AP-1 and NF-kappa B it did not induce either B cell proliferation or immunoglobulin secretion. PMID- 1520342 TI - A point mutation of c-Ki-ras gene was found in human esophageal carcinoma cell lines but not in primary esophageal carcinomas. AB - Activation of the ras oncogene in primary human esophageal carcinomas and cell lines established from such carcinomas was analyzed using the polymerase chain reaction (PCR)-direct sequencing method. This analysis revealed a GC----AT transition at the second base in the 12th codon of the c-Ki-ras gene in TE1 and TE2 esophageal carcinoma cell lines. In contrast, no point mutation was detected in the 12th, 13th, and 61st codon of the c-Ki-ras and c-Ha-ras gene in 31 primary esophageal carcinomas including those from which TE1 and TE2 cell lines were established. These results demonstrate that while activation of the c-Ki-ras gene by point mutation occurred in a subset of esophageal carcinoma cell lines during establishment of the cell lines, the activation events are not important in the transformation of human esophageal epithelial cells. PMID- 1520343 TI - Methotrexate decreases thymidine kinase activity. AB - MTX cytotoxicity is not fully explained by its well-known inhibition of dihydrofolate reductase activity which leads to a decrease in the dTMP synthase reaction, since TdR kinase which converts TdR to dTMP could readily circumvent MTX action through this salvage activity. TdR kinase is of particular significance, since in various types of carcinoma cells its activity is orders of magnitude higher than that of dTMP synthase. To throw light on this problem, we tested the hypothesis that the impact of MTX treatment might in fact involve an inhibition or decrease in TdR kinase activity. Injection in rat of MTX (i.p.) decreased TdR kinase activity in a time- and dose-dependent fashion in liver (t1/2 = 46 h; IC50 = 95 mg/kg), bone marrow (t1/2 = 10 h; IC50 = 5 mg/kg) and rapidly growing transplantable hepatoma 3924A (t1/2 = 56 h; IC50 = 5 mg/kg). Injection in rat of cycloheximide (15 mg/kg, i.p.), an inhibitor of protein biosynthesis, rapidly decreased TdR kinase activity in the hepatoma (t1/2 = 3.6 h); activities of other purine and pyrimidine synthetic enzymes, dTMP synthase, IMP dehydrogenase, GMP reductase and GMP synthase, declined at a markedly slower rate (t1/2 = 11, 11.6, 12 and 22 h, respectively). MTX, by curtailing purine and pyrimidine biosynthesis, limits product of TdR kinase which is more sensitive to unopposed protein degradation than other enzymes of nucleic acid biosynthesis. TdR kinase is a newly discovered target of MTX treatment. PMID- 1520344 TI - Augmentation of transient low-threshold Ca2+ current induced by GTP-binding protein signal transduction system in GH3 pituitary cells. AB - We characterized the effects of thyrotropin-releasing hormone (TRH; 500 nM) and guanosine 5'-0-3-thiotriphosphate (GTP gamma S; 50 microM) on two types of Ca2+ currents in pituitary-hormone-secretory GH3 cells and were surprised to find marked increases in transient, low-threshold Ca2+ currents (T currents) induced by extracellularly applied TRH or intracellularly applied GTP gamma S. The effect of TRH was blocked by intracellularly applied guanosine 5'-0-2-thiodiphosphate (GDP beta S; 100 microM). The increase in the T current was found to be accompanied by a decrease in long-lasting, high-threshold Ca2+ current (L current), in response to both TRH or GTP gamma S. These indicate that the enhancement of Ca2+ influx by TRH (500 nM) is largely conferred by T currents in GH3 cells. A reduced concentration of TRH (5 nM) still markedly increased the T current, but failed to decrease the L current. These data suggest that the augmentation of the T currents as well as depression of the L currents by TRH (500 nM), through the activation of a GTP-binding protein, may constitute an important regulatory mechanism of sustained pituitary hormone secretion in GH3 cells. PMID- 1520345 TI - Expression, purification and biochemical comparison of natural and recombinant human non-pancreatic phospholipase A2. AB - The gene coding for human non-pancreatic phospholipase A2 (npPLA2) was cloned in a eukaryotic expression vector and transfected into chinese hamster ovary (CHO) cells. A number of cell lines stably expressing npPLA2 were obtained. Northern analysis of these cell lines showed an abundant transcript of expected size 1200 nt. The recombinant enzyme was efficiently secreted in quantities up to 400 micrograms npPLA2 per liter culture medium in the most productive cell lines. npPLA2 was purified to homogeneity from conditioned medium as previously described (1). The recombinant npPLA2 migrated by SDS--PAGE as a single band with an apparent mass of 14,000. The recombinant enzyme displayed the pH-optimum, calcium dependence and substrate preference that were characteristic of the human platelet and synovial fluid enzymes. PMID- 1520346 TI - Vascular smooth muscle cells exhibit increased growth in response to elevated glucose. AB - Diabetes mellitus is associated with an increased risk of cardiovascular disease. In order to elucidate the association between hyperglycemia and vascular complications, the growth patterns of vascular smooth muscle cells were studied under high glucose conditions. We examined the effect of culturing porcine aortic smooth muscle cells (PVSMC) in high glucose (25 mM, HG) on total cell protein, cell volume, DNA synthesis and cell number. We observed that cells cultured in HG had higher total cell protein content which was associated with increased cell volume as compared to the cells cultured under normoglycemic conditions (5.5 mM glucose, NG). PVSMC cultured in HG also had 1.4 fold increased growth rate and a greater fetal calf serum-induced DNA synthesis rate compared to cells cultured in NG. These observations suggest for the first time that elevated glucose could lead to both hypertrophic and hyperplastic effects in PVSMC. We also examined protein kinase C (PKC) activities as well as the cellular levels of the 12 lipoxygenase product, 12-hydroxyeicosatetraenoic acid (12-HETE) in NG and HG as possible mechanisms for the enhanced growth effects in HG. The results show that PVSMC cultured in HG have increased PKC activity as well as increased levels of 12-HETE. Therefore hyperglycemia may be linked to accelerated vascular disease by increasing smooth muscle cell growth and proliferation. PMID- 1520347 TI - The primary structure of rat ribosomal protein L3. AB - The amino acid sequence of the rat 60S ribosomal subunit protein L3 was deduced from the sequence of nucleotides in a recombinant cDNA. Ribosomal protein L3 has 403 amino acids and has a molecular weight of 46,106. Hybridization of the cDNA to digests of nuclear DNA suggests that there are 7 to 9 copies of the L3 gene. The mRNA for the protein is about 1,400 nucleotides in length. Rat L3 is homologous to ribosomal proteins from other eukaryotes and to proteins from eubacterial, archaebacterial, and chloroplast ribosomes. PMID- 1520348 TI - Cold hard death, cold hard doctors. PMID- 1520349 TI - A question of "doing the right thing" or "doing the thing right". PMID- 1520350 TI - The effect of physician and patient gender on preventive medicine practices in patients older than fifty. AB - This study examined whether the sex of physicians and patients affected the preventive care of middle-aged and older patients of family physicians. The charts of 61 male and 75 female patients older than 50 years, whose primary physicians were third-year family practice residents, were reviewed to determine whether tests to screen for colorectal, breast, and cervical cancer had been offered to them in the previous 18 months by their primary physicians. Male residents had offered rectal examinations significantly more frequently than female residents to male patients older than 70. Female residents had offered mammograms, pelvic exams, and Pap smears significantly more frequently to women older than 50 than had male residents. Female residents had significantly higher rates of offering pelvic exams and Pap smears to women between the ages of 50 and 70, but this difference was not significant for women over 70. There were no significant differences in the number of refusals by male or female patients to male or female residents. Results suggest that the sex and age of the patient and the sex of the physician may play a role in differential rates of cancer screening. PMID- 1520351 TI - Unavoidable tragedies in Madison, Wisconsin: a third view. PMID- 1520352 TI - Advance directives about medical treatment. PMID- 1520353 TI - Early growth and clotting factors in adult life. PMID- 1520354 TI - Could an outbreak of poliomyelitis occur in the UK? PMID- 1520355 TI - A patient's charter for laboratories. PMID- 1520356 TI - Obesity in a high school football candidate: a case presentation. AB - A 14-yr-old male presented for medical clearance to play fall football for his high school team. He had stayed out of the prior spring football practice sessions after a shoulder injury on the first day of practice, but indicated no other positive responses to the standard medical questionnaire. He was severely overweight with height of 180 cm, weight 133.4 kg, and his estimated body fat was 36%. His examination was otherwise not revealing. He demonstrated poor aerobic fitness, exercise-induced bronchospasm, residual left shoulder weakness, and a dyslipoproteinemia on further medical evaluation. He was disqualified on an empirical basis, the attending physician making the clinical decision that it would be of greater harm than good for this adolescent to participate. However, there is little data and no established guidelines for this type of situation. The overweight football athlete is a challenge to the sports medicine team, both in managing the condition and in determining athletic eligibility. PMID- 1520358 TI - An old discussion: the "domino-donor" operation in heart and lung transplantation. PMID- 1520357 TI - Geniculate neuralgia. PMID- 1520359 TI - Tuberculosis in Australia. PMID- 1520360 TI - Biofeedback training for myopia control. PMID- 1520361 TI - BVA policy on animal welfare. PMID- 1520362 TI - Eccrine epithelioma: an enigma or a chimera? PMID- 1520363 TI - Osteosarcomatous changes in malignant melanoma. PMID- 1520364 TI - A hyperventilation interpretation of the termination of panic attacks: a reply to van den Hout, de Jong, Zandbergen and Merckelbach. AB - This paper summarizes the brief publication history of how a hyperventilatory positive-feed-back-loop theory of panic attacks explains the termination of panic attacks. A cautionary note is suggested when interpreting generalizations pertaining to panic attacks in panic-disorder sufferers in the everyday world made from laboratory findings based on healthy asymptomatic subjects. PMID- 1520365 TI - Persistent pleural effusion and post-traumatic subarachnoidal-pleural fistula. PMID- 1520366 TI - Nylon cable bands. PMID- 1520367 TI - Treatment for alcohol-abusing workers. PMID- 1520368 TI - Clinical problem-solving: trapped by an incidental finding. PMID- 1520369 TI - Clinical problem-solving: trapped by an incidental finding. PMID- 1520370 TI - Rhabdomyolysis associated with cranial diabetes insipidus. PMID- 1520371 TI - Gangrenous cholecystitis secondary to Candida tropicalis infection in a patient with leukemia. PMID- 1520372 TI - Eating disorder and childhood sexual abuse. PMID- 1520373 TI - Developing training themes from HRH's delivery. PMID- 1520374 TI - Training in HMOs. PMID- 1520375 TI - Experience with full thickness scalp burns. PMID- 1520376 TI - More information on SANEs in Houston. PMID- 1520377 TI - Resuscitation after cardiac arrest outside the hospital. PMID- 1520378 TI - The Patient Self-Determination Act. PMID- 1520379 TI - Lengths-of-stay and queues. PMID- 1520380 TI - Black-white differences in blood pressure. PMID- 1520381 TI - Left retroperitoneal approach for inflammatory abdominal aortic aneurysms. PMID- 1520382 TI - Cold hard death, cold hard doctors. PMID- 1520383 TI - Cold hard death, cold hard doctors. PMID- 1520384 TI - Animal rights. PMID- 1520385 TI - Sensitivity to angiotensin and the risk for hypertension. PMID- 1520386 TI - Psychiatrist case managers. PMID- 1520387 TI - Defense Health Agency. PMID- 1520388 TI - Morbidity and mortality associated with primary and repeat operations for ovarian cancer. PMID- 1520389 TI - Case of fulminant Reye's syndrome. PMID- 1520390 TI - Alternatives to standard hemorrhoidectomy. PMID- 1520391 TI - The analysis of failure time data in crossover studies. PMID- 1520392 TI - Associations between malaria and respiratory signs. PMID- 1520394 TI - Gallbladder disease and angina pectoris. PMID- 1520393 TI - Pharmacologic stress echocardiography. PMID- 1520395 TI - Born to it. PMID- 1520396 TI - DNA fingerprint matches. PMID- 1520397 TI - SHEA's initiative for confronting the cost-quality conundrum. The Society for Hospital Epidemiology of America. PMID- 1520398 TI - Molecular and prospective phenotypic characterization of a pedigree with familial Alzheimer's disease and a missense mutation in codon 717 of the beta-amyloid precursor protein gene. AB - We present prospective clinical and neuropathologic details of a pedigree segregating familial Alzheimer's disease (FAD) associated with a mutation (G----A substitution) at nucleotide 2149 in exon 17 of the amyloid precursor protein (APP) gene. This mutation, which is predicted to cause the missense substitution of isoleucine for valine at codon 717 of APP, cosegregated perfectly with the FAD trait (lod score = 3.49 at theta = 0.00). The earliest clinical manifestations of the disease relate to deficits in memory function, cognitive processing speed, and attention to complex cognitive sets. These changes occurred in the absence of changes in nonmemory language and visuospatial functions. The neuropathologic features of FAD associated with the APP717 mutation in this family include severe neuronal loss, abundant neurofibrillary tangles, amyloid plaques, and amyloid angiopathy. These results provide independent confirmation that mutations in the APP gene are linked to the FAD trait in some families. PMID- 1520399 TI - A case against exit exams. PMID- 1520400 TI - APP-collagen interaction is mediated by a heparin bridge mechanism. AB - The amyloid precursor protein (APP) is a glycoprotein consisting of at least four isoforms derived from a single gene by a process of alternative splicing. The membrane-bound forms of APP have been suggested to have adhesive properties and to mediate neural cell adhesion. Previous studies have demonstrated the ability of Fab' fragments of antibodies to extracellular domains of APP to inhibit neural cell binding to a collagen substrate, suggesting a physiological role for the collagen-binding properties of APP. The binding of APP has been demonstrated to be specific for type IV collagen, and no binding to other extracellular matrix components, including fibronectin and laminin, was detected. The APP-collagen binding appeared to be mediated by a heparin-bridge mechanism, since the binding was abolished by the addition of excess heparan or heparinase. These results were observed by both a homogenate-collagen binding assay and a cell-surface adhesion assay, thus providing further evidence for the adhesion role of APP. They also pose the question of the possible role of the heparin-binding properties of APP in the genesis of the neuritic plaques characteristic of Alzheimer's disease. PMID- 1520401 TI - Effects of aluminum speciation on murine neuroblastoma cells. AB - Murine neuroblastoma cells behave differently in the presence of Al(acac)3 [acac = 2,4-pentanedionate; acetylacetonate] or Al(malt)3 [malt = 3-hydroxy, 2-methyl, 4-pyronate; maltolate] with respect to Al(lac)3 [lac = 2-hydroxypropionate; lactate]. Thus, a remarkable cytotoxic effect was observed in the first case; on the contrary, an evident cytostatic and neuritogenic effect was produced by aqueous Al(lac)3. The hydrolytically stable complexes Al(acac)3 and Al(malt)3 were both toxic in the concentration range of 0.10-0.30 and 0.10-0.50 mM, respectively, over 24 h. In contrast with this behavior Al(lac)3 displayed a potent cytostatic activity with induction of neurites at 0.2-10 mM. Al(OH)3 manifested biological effects comparable to those exhibited by Al(lac)3. AlPO4 was also cytostatic and led to a morphological differentiation of the neuroblastoma cells, qualitatively different from that elicited by Al(lac)3. The morphological effects induced by Al(lac)3, Al(OH)3, and AlPO4 were irreversible. PMID- 1520402 TI - A fetal type of Minamata disease. An autopsy case report with special reference to the nervous system. AB - Our knowledge concerning the pathology of fetal cases of human Minamata disease (methylmercury poisoning) is relatively limited. We report here a case with description of the distribution of mercury in the systemic organs, and the ultrastructural changes of the nervous system after a survival of 29 yr. The patient was a female born in 1957, with a body wt of 3000 g, who died in 1987. She carried a diagnosis of cerebral palsy, and had a convulsion at age 3 yr. Mercury levels in her mother's hair were 101 micrograms/g at the time of examination in 1959. At autopsy, the body measured 43 cm and weighed 23 kg. The brain weighed 920 g and showed marked cerebral atrophy, mild neuronal loss in the calcarine, postcentral and precentral cortices, cerebellar atrophy, and segmental demyelination of peripheral nerves. Mercury granules were present in the brain, kidney, and liver. Ultrastructural examination of the calcarine, post- and precentral cortices, and cerebellar cortices, showed severe atrophy of nerve cells, with a decrease in rough ER and an increase in nuclear chromatin and preservation of mitochondria. Autophagosomes were increased in number. In addition, high electron density, globular and dense bodies, measuring 0.3-1.8 microns in diameter, were found, surrounded by limited membrane, within both cerebral and cerebellar neurons. In the cellebellum, synapses were well preserved. PMID- 1520403 TI - The role of lipid peroxidation in the possible involvement of membrane-bound monoamine oxidases in gamma-aminobutyric acid and glucosamine deamination in rat brain. Focus on chemical pathogenesis of experimental audiogenic epilepsy. AB - Incubation of rat brain synaptosomes and mitochondria with LPO inducers (Fe2+ and ascorbate) was accompanied by a decrease of deamination of serotonin (substrate of MAO-A) in mitochondria, but not in synaptosomes, with simultaneous stimulation of GABA and GLCA deamination, apparently owing to modification of catalytic properties of brain membrane-bound MAO. Oxidation of PEA (substrate of MAO-B) was insignificantly altered in both fractions. Reactions of deamination of serotonin, GABA, and GLCA (but not PEA), were highly sensitive to a selective inhibitor of MAO-A pyrazidol (pyrlindole). Isoniazid and hydrazides of quinoline carbonic acids (inhibitors of both modified MAO and copper-containing amine oxidases) strongly inhibited deamination of GABA and GLCA. During epileptiformic seizures in rats, genetically selected for high incidence of audiogenic epilepsia, stimulation in brain synaptosomes and mitochondria of LPO was observed. This was accompanied by a marked decrease in serotonin and PEA deamination, with a simultaneous increase in GABA and GLCA deamination in both fractions. The data obtained suggest that appearance of GABA-deaminating activity owing to modification of catalytic properties of MAO, might be an essential pathogenetic component in the development of epileptic seizures. PMID- 1520404 TI - Platelet MAO-B activity and vitamin B12 in old age dementias. AB - Platelet MAO-B activity, serum vitamin B12 levels, and plasma folate were measured in patients suffering from presenile (AD) and senile (SDAT) dementia of Alzheimer-type, and vascular dementia (VD). MAO-B was higher in the SDAT group than in AD and controls. An inverse relationship between MAO-B activity and vit. B12 levels was documented in the whole group and in each category studied; furthermore, MAO-B was positively related to age. All the patients were then divided into two groups, according to vit. B12 levels (Group I: less than 200 pg/mL; Group II: greater than or equal to 200 pg/mL); Group I showed a significantly higher MAO-B activity with respect to Group II. The results indicate the existence of a negative association between platelet MAO-B activity and serum levels of vitamin B12 and confirm the existence of biological differences between presenile and senile dementia of Alzheimer type. PMID- 1520406 TI - Potential role of viruses in neurodegeneration. AB - Viruses have the capacity to induce alterations and degenerations of neurons by different direct and indirect mechanisms. In the review, we have focused on some examples that may provide new avenues for treatment or altering the course of infections, i.e., antibodies to fusogenic virus membrane proteins, drugs that interfere with lipid metabolism, calcium channel blockers, immunoregulatory molecules, and, and inhibitors of excitotoxic amino acids. Owing to their selectivity in attack on regions of nervous tissue, governed by viral factors and by routes of invasion, viral receptors or metabolic machineries of infected cells, certain viral infections show similarities in distribution of their resulting lesions in the nervous system to that of the common human neurodegenerative diseases (namely, motor neurons disease, Parkinson's disease, and Alzheimer's disease). However, it should be emphasized that no infectious agent has as yet provided a complete animal model for any of these diseases, nor has any infectious agent been linked to them from observations on clinical or postmortem materials. PMID- 1520405 TI - Primary cultures of astrocytes from rat as a model for biotin deficiency in nervous tissue. AB - The activities and biotin-dependence of the three mitochondrial biotin-dependent carboxylases: pyruvate carboxylase, propionyl CoA carboxylase, and beta methylcrotonyl CoA carboxylase of primary culture of astrocytes have been examined. An increase of the three mitochondrial carboxylase activities was observed during cell growth, as was the case for developing rat brain. Mitochondrial carboxylase activities from 3-wk-old primary cultures of astrocytes were higher than those in the neonatal rat brain. When astrocytes were grown in a 10% serum-enriched medium supplemented with avidin to bind biotin, the mitochondrial carboxylase activities were reduced to 15% of control value. Consistent with these results, after 3 wk in culture, the 3-hydroxyisovaleric acid concentration in the growth medium was tenfold higher than the controls. In this culture condition, cellular growth and the nonbiotin-dependent enzyme, glutamine synthetase, were not modified with respect to control. Primary cultures from newborn rat brain hemispheres are suggested as an experimental approach to the study of biotin deficiency in nervous tissue. PMID- 1520407 TI - Protein kinase C activity in permanent focal cerebral ischemia. AB - Protein kinase C (PKC) activity was investigated in a model of focal stroke in the rat. Following 6 h of left middle cerebral artery occlusion, rat brains were frozen in situ. In the peripheral ischemic zone, total PKC activity declined by close to two-thirds (1.07 +/- 0.35 vs 2.77 +/- 0.12 nmol/min/mg protein; p less than 0.05, n = 4), and the proportion of total activity associated with the particulate fraction decreased from 33.3 +/- 1.5% to 16.2 +/- 1.4% (p less than 0.01, n = 4). Thus, overall particulate PKC activity in the ischemic zone was less than 20% of control. The cerebral energy metabolite profile of tissue from the ipsilateral hemisphere, corresponding to the region where samples were obtained for PKC activity assay, suggests that this tissue may have been part of the ischemic penumbra before further deterioration. PMID- 1520408 TI - Impact of the USMLE step 1 on teaching and learning of the basic biomedical sciences. United States Medical Licensing Examination. AB - Medical licensure in the United States is in transition. In June 1991, the National Board of Medical Examiners (NBME) made major modifications in the content, format, pass/fail standards, and score reports of the NBME Part I examination. This year, Part I became Step 1, the first of three components of the United States Medical Licensing Examination (USMLE), which will shortly be the sole examination pathway to initial licensure for allopathic physicians. This essay describes Step 1, reviews the phase-in plans for the USMLE, and discusses the potential impact of both on medical schools' teaching and students' learning of the basic biomedical sciences. The authors recommend that medical schools (1) abandon the use of Step 1 as a sole criterion for student promotion to the third year and (2) carefully review other examination-related requirements for promotion and graduation. PMID- 1520409 TI - The psychological basis of problem-based learning: a review of the evidence. AB - Several potential advantages for students' learning are claimed for problem-based learning (PBL). Students in PBL curricula may be more highly motivated; they may be better problem solvers and self-directed learners; they may be better able to learn and recall information; and they may be better able to integrate basic science knowledge into the solutions of clinical problems. Although some of these claims find theoretical support from the literature on the psychology of learning, to date there has been no review of the experimental evidence supporting the possible differences in students' learning that can be attributed to PBL. In this review article, the authors examine each claim critically in light of that evidence. They conclude that (1) there is no evidence that PBL curricula result in any improvement in general, content-free problem-solving skills; (2) learning in a PBL format may initially reduce levels of learning but may foster, over periods up to several years, increased retention of knowledge; (3) some preliminary evidence suggests that PBL curricula may enhance both transfer of concepts to new problems and integration of basic science concepts into clinical problems; (4) PBL enhances intrinsic interest in the subject matter; and (5) PBL appears to enhance self-directed learning skills, and this enhancement may be maintained. PMID- 1520410 TI - Introducing students to the role of folk and popular health belief-systems in patient care. PMID- 1520411 TI - Using the computer-assisted medical problem-solving (CAMPS) system to identify students' problem-solving difficulties. PMID- 1520412 TI - Pass-fail grading fails to meet the grade. PMID- 1520413 TI - Learning about students' attitudes toward entering medical careers. PMID- 1520414 TI - Impact of emergency psychiatry training on residents' decisions to hospitalize patients. PMID- 1520415 TI - Romantic relationships between physicians and patients. PMID- 1520416 TI - Comparing the characteristics of schools that produce high percentages and low percentages of primary care physicians. AB - To examine whether the medical school environment is important in influencing students to choose careers in primary care, the authors in 1991 compared certain characteristics of the environments of schools that produced high percentages of primary care physicians with those of schools that produced low percentages over a five-year period. The authors used the American Medical Association Physician Masterfile to identify the percentage of graduates of each of 121 medical schools for the period 1981-1985 who entered primary care specialties. They then compared the 25 schools that produced low percentages (22-29%) with the 25 schools that produced high percentages (39-56%). The results demonstrate important differences between the two groups of schools in their commitments to primary care education, their research programs, and their clinical environments supporting required clerkships. The authors conclude that a school's educational environment is an important factor in influencing some students to pursue careers in primary care medicine. PMID- 1520417 TI - Screening test length for sequential testing with a standardized-patient examination: a receiver operating characteristic (ROC) analysis. AB - The feasibility of using sequential testing (i.e., using a screening test) to reduce the length and expense of a performance-based examination with standardized-patient cases was demonstrated previously. In the present study, quantitative criteria rather than practical considerations were used to determine optimal values for the length of the screening test (i.e., number of cases) and the location of the screening pass-fail cutoff (i.e., its relation to the mean of the pass levels for the different cases). Data were derived from five classes of senior students at the Southern Illinois University School of Medicine, 1987 1991. Specifically, receiver operating characteristic (ROC) curves were plotted for screening tests of varying lengths, with the points on each ROC curve corresponding to different pass-fail cutoffs on the screening test. The results showed that good accuracy can be attained with a screening test that is only one third the length of the full examination and that the cutoff for this screen should be set slightly above the mean of the case pass levels to maximize sensitivity and specificity. The authors conclude that their study demonstrates the value of an ROC analysis in evaluating the psychometric properties of a screening test in sequential testing. PMID- 1520418 TI - Health education programs in U.S. medical schools. AB - To examine the status of teaching programs on health education in undergraduate medical education, the author in 1990-91 surveyed representatives of all 126 U.S. medical schools. Of the 97 institutions that responded, 63 (65%) offered instruction in patient education and 72 (74%) offered instruction in community health promotion. The responses indicated that a number of departments participated in instruction and that diverse methods of instruction and evaluation were used. Opinions of the representatives regarding the importance and adequacy of instruction in health education were quite favorable. The author concludes that more information is needed to determine the effectiveness of the instructional programs and their impact on the quality of medical care. PMID- 1520419 TI - Teaching the process of obtaining informed consent to medical students. AB - This paper describes a unit on the informed consent process taught to 119 first year students at the Michigan State University College of Osteopathic Medicine in 1988-89. The unit consisted of a pretest and a posttest, a lecture, readings, small-group discussions, a model videotaped interview, and the students' videotaped interviews with one of two simulated patients. In the interviews, the students were most successful in establishing rapport and engaging the patients in discussions of treatment alternatives, and were less successful in perceiving the patients as unique individuals and in dealing with situations that involved conflict or confrontation. The authors suggest that curricula can be enhanced by focusing on the importance of patients' participation in the informed consent process. PMID- 1520420 TI - How the topic of homosexuality is taught at U.S. medical schools. AB - In 1991 the authors surveyed all U.S. medical schools to assess both the number of curriculum hours devoted to the topic of homosexuality and the instructional strategies employed in its academic treatment; responses were sought from faculty with responsibility for teaching the topic (mostly directors of medical student education in psychiatry). Of the 126 schools, 82 (65%) responded. The mean number of hours reported was 3 hours and 26 minutes, with significant differences based on geographic region. The most frequently cited strategy was lectures in human sexuality, followed distantly by panel presentations and meetings with gay men or lesbians (both health care providers and others). To enhance sensitivity and comfort with gay and lesbian issues and to counter stereotypic responses, the authors propose that the topic of homosexuality be wholly integrated throughout the curriculum. PMID- 1520421 TI - Assessing personal occupational safety and health training for students at U.S. medical schools. AB - Medical students potentially are exposed to numerous occupational hazards. This study examined the training and preventive measures medical schools use to protect the health and safety of students. In late 1990, questionnaires were mailed to the 126 schools in the United States. One hundred (79%) responded, reporting numerous incidents of illness and injury. Of the 100 schools, 60 agreed with the statement that their students were adequately prepared to work safely; 11 disagreed, and 24 gave neutral responses (five did not respond to the statement). However, 36 indicated that they planned to revise health and safety training. The authors recommend that schools adopt policies, procedures, and a uniform curriculum regarding students' occupational safety and health. PMID- 1520422 TI - Prematriculation program grades as predictors of black and other nontraditional students' first-year academic performances. AB - This study explored the relative strengths of select background variables, including grades in a summer prematriculation program (SPP), as predictors of students' first-year academic performances. During the years 1980-1989, 115 black and other nontraditional prematriculants at the Medical College of Georgia School of Medicine attended a four-week SPP featuring courses in biochemistry, anatomy, and immunology. Canonical correlation analysis revealed that the combination of undergraduate grade-point average (GPA) and SPP grades in biochemistry and anatomy was the best predictor of the students' academic performances based upon their first-year grades in biochemistry, anatomy, and microbiology, and upon their GPAs for all first-year basic science courses. The authors conclude that SPP grades can be used to identify the specific academic weaknesses of nontraditional students at highest risk of falling into academic jeopardy. PMID- 1520423 TI - Comparing the transfusion medicine content of the NBME's examinations in 1984 1985 and 1989-1990. AB - Recognition of the seriousness of transfusion-transmitted diseases has been demonstrated by U.S. medical schools through the integration of transfusion medicine (TM) content into their curricula. To evaluate the degree to which these changes in curricula have been reflected in the National Board of Medical Examiners' (NBME) examinations, a study conducted in 1991 evaluated the proportions of TM-related items on Parts I and II of the NBME examinations for 1984-1985 versus 1989-1990. Both Part I (basic sciences) and Part II (clinical sciences) demonstrated significant gains in TM items between the comparison periods (p less than .001), with Part II having the higher gain. An analysis of students' knowledge revealed that students in 1989-1990 tended to perform better on TM items than on examination items generally. The increases in TM content and student performance on TM items on the 1989-1990 examinations suggest that the national effort to expand and improve teaching of TM in U.S. medical schools has been effective. PMID- 1520424 TI - Attitudes of medical school faculty toward gifts from the pharmaceutical industry. AB - The American Medical Association (AMA) has recently published guidelines for the receipt of gifts from industry representatives. To examine faculty members' attitudes toward that AMA policy as it pertains to gifts from the pharmaceutical industry, the authors surveyed the faculty of the University of Kentucky College of Medicine in 1991. Of 462 faculty members, 248 (54%) completed the questionnaires. The faculty generally agreed with the AMA guidelines. A majority of the faculty believed that personal relationships had the potential to influence prescribing patterns but that gifts, in general, did not greatly influence prescribing behaviors. Compared with the 169 M.D. faculty, the 69 Ph.D. faculty significantly favored more restrictive policies (p less than .001). The authors discuss both the ethical considerations and the utility of guidelines for physician-industry interactions. PMID- 1520425 TI - Students' attitudes toward informed consent and the physician-patient relationship in regard to human tissue research. PMID- 1520426 TI - Comparing medical students' and residency directors' ratings of criteria used to select residents. PMID- 1520427 TI - Using an in-training examination to assess and promote the self-evaluation skills of residents. PMID- 1520428 TI - Guidelines for faculty involvement in commercially supported continuing medical education. AAMC Ad Hoc Committee on Misconduct and Conflict of Interest in Research. AAMC Subcommittee on Conflict of Interest in Continuing Medical Education. PMID- 1520429 TI - Multiday driving patterns and motor carrier accident risk: a disaggregate analysis. AB - A method has been developed to estimate the relative accident risk posed by different patterns of driving over a multiday period. The procedure explicitly considers whether a driver is on duty or off duty for each half hour of each day during the period of analysis. From a data set of over 1,000 drivers, nine distinct driving patterns are identified. Membership in the patterns is determined exclusively by the pattern of duty hours for seven consecutive days; for some drivers an accident occurred on the eighth day while others had no accident, therefore each pattern can be associated with a relative accident risk. Additional statistical modeling allowed the consideration, in addition to driving pattern, of driver age, experience with the firm, hours off duty prior to the last trip and hours driving on the last trip (either until the accident or successful completion of the trip). The finding of the modeling is that driving patterns over the previous seven days significantly affect accident risk on the eighth day. In general, driving during the early and late morning (e.g., midnight to 10 A.M.) has the highest accident risk while all seven other multiday patterns had indistinguishable risk. Consecutive hours driven also has a significant effect on accident risk: the first hour through the fourth hour having the lowest risk with a fluctuating increase in risk to a maximum beyond nine hours. Driver age and hours off duty immediately prior to a trip do not appear to affect accident risk significantly. These findings quantitatively assess the relative accident risk of multiday driving patterns using data from actual truck operations. Further research is recommended in the areas of refining model structures, adding explanatory variables (such as highway type), and testing more complex models. PMID- 1520430 TI - Empirical Bayes approach to the estimation of "unsafety": the multivariate regression method. AB - There are two kinds of clues to the unsafety of an entity: its traits (such as traffic, geometry, age, or gender) and its historical accident record. The Empirical Bayes approach to unsafety estimation makes use of both kinds of clues. It requires information about the mean and the variance of the unsafety in a "reference population" of similar entities. The method now in use for this purpose suffers from several shortcomings. First, a very large reference population is required. Second, the choice of reference population is to some extent arbitrary. Third, entities in the reference population usually cannot match the traits of the entity the unsafety of which is estimated. To alleviate these shortcomings the multivariate regression method for estimating the mean and variance of unsafety in reference populations is offered. Its logical foundations are described and its soundness is demonstrated. The use of the multivariate method makes the Empirical Bayes approach to unsafety estimation applicable to a wider range of circumstances and yields better estimates of unsafety. The application of the method to the tasks of identifying deviant entities and of estimating the effect of interventions on unsafety are discussed and illustrated by numerical examples. PMID- 1520431 TI - The effectiveness of motor carrier safety audits. AB - In 1986 the federal government expanded its program of company inspections for enforcement of motor carrier safety regulations. We find that many parts of these inspections are unrelated to the safety performance of firms. Never the less, reinspection of firms found to be unsatisfactory in a previous inspection does appear to bring about a substantial improvement in their safety performance. However, such firms represent a small fraction of the industry, and the probability of being inspected is very low. Thus, the program does not appear to have resulted in a detectable improvement in the accident rate of the industry. PMID- 1520432 TI - Interactivity, information, and compliance cost in a consumer product warning scenario. AB - The effects of information content, physical interactivity, and cost of compliance on safe behavior of 356 subjects were examined using a common consumer product. The use of gloves for a "new formulation" consumer cleaning product was tested along with subject perceptions of the risk associated with the product's use. Results indicated that cost of compliance was the only variable that significantly affected the safe use of the product. Implications for consumer product safety and regulation are discussed. PMID- 1520433 TI - Can road traffic law enforcement permanently reduce the number of accidents? AB - In this paper it is argued that conventional analyses of road user adaptation to traffic law enforcement, based on parametric rational-choice theory, are flawed. Such analyses only consider road-user actions as a response to enforcement level and penalty size and do not simultaneously consider enforcement as a response to road-user behaviour. If each party is considered a rational agent who adapts to the other's behaviour, the proper way to analyze the outcomes is by the way of game theory. A game-theoretic model is presented and the main implications are: (i) most attempts at enforcing road traffic legislation will not have any lasting effects, either on road-user behaviour or on accidents; (ii) imposing stricter penalties (in the form of higher fines or longer prison sentences) will not affect road-user behaviour; (iii) imposing stricter penalties will reduce the level of enforcement; (iv) implementing automatic traffic surveillance techniques and/or allocating enforcement resources according to a chance mechanism, and not according to police estimates of violation probability, can make enforcement effects last, but both alternatives are difficult to implement. Relevant empirical studies are reviewed, and they seem to support the conclusions arrived at by the game-theoretic model. PMID- 1520434 TI - Introducing beer sales at a Canadian ball park: the effect on motor vehicle accidents. AB - The impact of introducing the legal sale of beer in a Toronto stadium on drinking driving accidents is investigated. The results suggest that a greater proportion of accidents in the postgame time are alcohol-related when compared to pregame times and to control times. No significant effect was found, however, for the introduction of legal beer sales, suggesting that drinking was common before the public sales policy. PMID- 1520435 TI - Falls in 84- to 85-year-old people living at home. AB - The present study is a part of the Swedish longitudinal population study "70-year old people in Gothenburg". The aim of the present study was to analyse retrospectively incidence, circumstances, and consequences of falls during one year among 741 home-living people aged 84-85. A comparison of social and medical characteristics of fallers and non-fallers aged 85 was performed. Information was collected by interviews and clinical examinations. In 1986/1987, 732 home-living people (244 men and 488 women), aged 85 gave information about falls during the last year. Three hundred and one (41%), 97 men and 204 women, had fallen at least once during the last year, mainly indoors. No sex difference was found in incidence. The most dominant triggering causes of falls were stumbling, dizziness, and feebleness. In 80% of the falls an injury occurred, of which every fourth was a fracture. A multivariate regression procedure showed that dizziness, vertigo and unsteadiness, transient ischemic attacks, antidepressant drugs, and poor subjectively experienced health characterized the fallers. Mortality rate of those between 85 and 88 years of age showed no association with falls. PMID- 1520436 TI - Some biases in the alcohol investigative process in traffic fatalities. AB - This study compares data regarding alcohol involvement from police records and from chemical analyses of body fluids taken prior to or after death of 121 traffic fatalities in Washtenaw County, Michigan. Differences regarding the choice of who will or will not be screened for alcohol were found. The police and emergency room personnel were more likely to focus on males and drivers, while medical examiners were less biased. The police documented whether or not drinking took place in only 36% of the cases and suspected drinking in only half of these cases. Males and at-fault drivers were most likely to be investigated. Blood alcohol level was measured before death in 11 of 29 emergency room treated victims, with 10 (91%) positive samples. All but two of those tested before death were drivers, and all but one were males. After death, blood alcohol was measured in 47% of the 121 cases, with a higher proportion of males and motor-vehicle occupants tested, compared to females and pedestrians. Alcohol was detected in 63% of the samples. A lower mean blood alcohol concentration was found in victims who received intravenous treatment, and a higher proportion of positive samples was found in victims who died immediately in the crash. Thus, the frequency of alcohol-related traffic fatalities varied between the different data sources. The police records revealed 51%, the emergency records 91%, and the medical examiner records 63% with alcohol involvement. This wide discrepancy has the potential of leading to erroneous results here and possibly in studies done elsewhere.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1520437 TI - Traffic volume and collisions involving transit and nontransit vehicles. AB - This study reports an analysis of collisions occurring between public transit vehicles operated by the San Francisco Municipal Railway System (Muni), the public transit agency for the City of San Francisco, and nontransit vehicles. The analysis, focusing on weekday collisions during 1987, demonstrated a strong association between hourly transit collisions rates and hourly traffic volume. The collision rate varied from 0.01 per 1,000 Muni vehicle-hours of operation during the interval 5 A.M. to 6 A.M., a time of very low traffic volume, to 0.93 (approximately 1 collision per 1,000 Muni vehicle-hours of operation) during the interval 5 P.M. to 6 P.M., a time of very high traffic volume. Using a power function to predict either the total number of collisions, or the rate of collisions per 1,000 Muni vehicle-hours, almost 90% of total variation was accounted for by traffic volume. A very similar pattern was found for collisions judged either avoidable or unavoidable. A peak in the collision rate between 2 A.M. and 3 A.M. could not be accounted for by traffic volume alone. That peak occurred in the one-hour interval following the 2 A.M. closing of bars in San Francisco, and was composed entirely of a sharp increase in unavoidable collisions. Increasing traffic volume appeared to operate through two mechanisms: (i) an increase in the number of opportunities for a collision, defined as a quantity proportional to the product of the number of Muni and non-Muni vehicles; (ii) an increase in the probability of a collision occurring between any given pair of vehicles. PMID- 1520438 TI - In vitro loss of alcohol from tissue conditioners. AB - The rate of alcohol loss from two tissue conditioners was investigated by applying them to complete denture record bases and immersing them in water in a sealed container. Samples were taken regularly and analysed by gas chromatography. The alcohol was found to leach out much more quickly than expected with the greatest loss occurring in the first 12 hours and peaking at approximately 60 hours. PMID- 1520439 TI - Color changes of porcelain surface colorants resulting from firing. AB - Differential loss of chrome from surface colorants during firing can make the prediction of final porcelain color difficult. This investigation was undertaken to assess the color change of nine extrinsic colorants during firing. Colorants were applied to metal-ceramic substrates, and color was measured both before and after firing using a colorimeter. CIE LAB color coordinates were obtained as a measure of the direction and quantity of color change. Color change for yellow (delta E*ab = 4.00) was significantly greater than that for the other groups (delta E*ab = 0.41-1.25). Changes in L*a*b* values for yellow samples were toward those of the controls. PMID- 1520440 TI - Wear of I-bar clasps and porcelain laminate restorations. AB - Partial-coverage porcelain laminate restorations, placed to provide undercut areas for I-bar direct retainers of removable partial dentures, were evaluated over simulated 2- and 5-year periods of placement and removal movements. SEM photomicrographs and computer imaging were used to quantify wear of the I-bar tips and the contacting laminate surfaces. These data were statistically compared to previously collected data of I-bar clasp tip wear against human enamel under the same experimental conditions. None of the laminate restorations debonded during this investigation. I-bars contacting laminates exhibited significantly more wear than I-bars contacting human enamel; however, the combined laminate-I bar wear compared to the combined enamel-I-bar wear produced no significant difference. PMID- 1520441 TI - The influence of the retromylohyoid extension on mandibular complete denture stability. AB - It has been a clinical impression that the retromylohyoid extension in complete mandibular dentures contributes to stability. This hypothesis was tested in six individuals by means of cineradiography and placement of a metal marker in the mandible and dentures during chewing exercises, with and without the relevant denture extension. Analysis of tracings of the movements of the markers revealed that statistically significant differences existed between first and second chewing experiences. Movement in a horizontal plane around a vertical axis, however, was common to all dentures during all chewing. It is concluded that the retromylohyoid extension has a stabilizing effect on complete mandibular dentures. PMID- 1520442 TI - Relationship of removable partial denture use to root caries in an older population. AB - The pattern and severity of root caries in a selected older population, living in the community and attending a general dental practice in Bexhill, East Sussex, England, is reported. A total of 146 patients were examined to determine the relationship among removable partial dentures, their design, and root caries. Of those patients, 57% wore removable dentures and had a higher prevalence of exposed root surfaces and root caries, particularly on abutment teeth. In addition, root caries lesions on abutment surfaces were found to be larger and more active than those on nonabutment surfaces. PMID- 1520443 TI - Efficacy of various spray disinfectants on irreversible hydrocolloid impressions. AB - This study evaluated the effectiveness of eight disinfectant sprays on irreversible hydrocolloid impressions contaminated with three microorganisms (Staphylococcus aureus, Mycobacterium phlei, or Bacillus subtilis) or mixed oral flora. Alcide LD, OMC II, Biocide, and Professional Lysol Spray were relatively ineffective under the test conditions. Sporicidin and 0.525% sodium hypochlorite were able to effect a 4-log10 (99.99%) reduction against S aureus only. A 4-log10 reduction in bacterial counts was achieved by 5.25% sodium hypochlorite and Impresept in all tests except against B subtilis. Full-strength sodium hypochlorite (5.25%) was the most effective disinfectant overall and required the shortest contact time. PMID- 1520444 TI - Bond strength of three nonaqueous elastomeric impression materials to a light activated resin tray. AB - The bonding of nonaqueous elastomeric impression materials to the impression tray is critical for an accurate impression; mechanical locks and adhesive materials are commonly used to enhance bonding. This study evaluated the bonding of three elastomeric materials to a light-polymerized resin tray. Roughening the tray surface prior to the application of an adhesive enhanced the bond. PMID- 1520446 TI - Measurements of dimensional accuracy using linear and scanning profile techniques. AB - Various measurement methods have been described for the determination of dimensional accuracy and stability of denture base materials. This investigation introduces a computerised coordinate measuring machine (CCMM) and compares it with two methods routinely used for assessment of the accuracy of fit of denture base materials. The results demonstrate that the three methods (digital calipers, optical comparator, and CCMM) are acceptable for linear measurement. The CCMM was also used in its scanning mode to define and to quantify the contour changes of the resin bases. The advantages of the CCMM become apparent when two-dimensional changes require assessment. PMID- 1520445 TI - Tensile strength of three resin cements following two alloy surface treatments. AB - Retainers for composite retained prostheses ("Maryland bridges") have traditionally relied upon an etched base metal alloy for micromechanical retention. This study compared the tensile bond strength of three resin cements using two alloy surface treatments. Rexillium III and Olympia disks were cast, oxidized, and given simulated porcelain firings. Paired specimens were cemented with Comspan, Panavia EX, or C & B Metabond after air abrasion with aluminum oxide or silicoating. Air-abraded Olympia disks were tin plated prior to luting with Panavia EX. Electrolytically etched Rexillium III specimens luted with Comspan served as controls. Specimens were thermocycled and tested in tension. Highest tensile bond strengths were achieved with: (1) Olympia specimens, where the bonding surface was air abraded but tin plated before cementation with Panavia EX, and (2) Rexillium III specimens, where the bonding surface was air abraded or silicoated and the disks were cemented with C & B Metabond. PMID- 1520447 TI - An analysis of edentulous maxillary arch width and palatal height. AB - This study involving 500 edentulous patients (250 males, 250 females) was undertaken to introduce a dimensionless factor termed the "palatal height ratio," defined as the ratio of the width of the edentulous maxillary arch to the height of the palate. The authors categorized the height, width, and anteroposterior dimensions of the edentulous maxillae. Measurements were made on diagnostic casts at five defined points. The difference between males and females was statistically analyzed and the variables were categorized. The results of this study may be helpful for a better standardization of the same variables in future studies. PMID- 1520449 TI - A philosophy of dental practice. PMID- 1520448 TI - A comparison of two methods for removing zinc oxide-eugenol provisional cement. AB - Two methods of removing zinc oxide-eugenol (ZOE) luting cement from amalgam were compared by determining their effect on the tensile bond strength of amalgam cylinders luted together using a 4-META resin cement. The samples were examined using scanning electron microscopy and energy dispersive x-ray analysis. Results showed that mechanical cleansing with pumice leaves ZOE residue mixed with pumice, which inhibits bonding, while the bond strength of samples cleansed with a dental degreasing agent was similar to that of an uncontaminated control group. PMID- 1520451 TI - Why does it take so long? PMID- 1520450 TI - Heat-pressed ceramics: technology and strength. AB - The flexural strength of a new heat-pressed ceramic material (IPS-Empress) was measured before and after pressing and/or simulated firing treatments (eg, veneering, surface coloring, glazing). Heat pressing the material significantly improved its flexure strength whereas heat treating the material alone did not. Additional firings (heat treatments) after heat pressing further increased material strength. The final strength values ranged between 160 and 180 MPa and were comparable to some other all-ceramic systems. No clinical implications were drawn from these data. PMID- 1520452 TI - Effects of ion exchange on hardness and fracture toughness of dental ceramics. AB - Dental ceramics generally fail because of the growth of microscopic surface flaws that form during processing or finishing or that result from surface impact during service. The ion-exchange process has been shown to be effective in improving the flexural strength of most dental porcelains through the development of a compressive surface layer. The Vickers hardness and crack resistance of several commercial dental ceramics were determined by indentation techniques. The results of this investigation indicate that ion-exchange reinforcement can significantly improve the resistance of the ceramic surface to crack propagation with little effect on apparent surface hardness. PMID- 1520453 TI - Mechanical properties of new denture resins polymerized by visible light, heat, and microwave energy. AB - Properties of seven newer resins polymerized using a water bath, microwave energy, or by visible light were measured. Generally, the new resins were harder and less flexible but had lower impact strength than did the heat-polymerized, rubber-modified resin (Lucitone). The light-activated urethane dimethacrylate resin (Triad) was the least flexible. Microwave polymerization improved the modulus of elasticity of two resins, decreased the impact strength of one, and had little effect on the properties of two other resins. PMID- 1520454 TI - Investigation of the effect of magnetic retention systems used in prostheses on buccal mucosal blood flow. AB - The purpose of this study was to investigate the probable effects of the magnetic field produced by dental magnets on neighboring capillary circulation. Ten subjects were used. Transparent acrylic resin devices were prepared to receive the dental magnets and were used continually by subjects except during sleep. The maxillary buccal mucosal blood flow was measured on both sides (control and experimental) in the same subjects before the use of dental magnets and after 3, 7, 15, 30, and 45 days by the 133Xe clearance technique. Upon analysis it was found that the difference in blood flow between the control and experimental sides was insignificant (P greater than .05). The decrease in blood flow as time progressed was attributed to the pressure exerted by the oral devices rather than by the effect of the magnetic field. PMID- 1520455 TI - Movement between centric relation contact position and the intercuspal position. AB - Casts of 42 patients free from temporomandibular joint problems were mounted on an articulator in centric relation contact position. The movement of the horizontal axis of rotation was measured when the casts were moved from centric relation contact position to the intercuspal position. Measurements of the vertical and horizontal movements of the incisal pin were also made during this movement. There was a highly significant correlation between the movement of the horizontal axis in the horizontal plane and the ratio of vertical to horizontal movement as measured at the incisal pin. The greater this ratio was, the smaller the horizontal movement of the axis was; the smaller the ratio (the larger the horizontal component) was, the larger was the horizontal movement of the axis. The clinical implications are discussed. PMID- 1520456 TI - The effect of clasp form on permanent deformation. AB - This study was conducted to discover whether a relationship exists between clasp width-thickness ratios and wear or deformation. Five different forms of circumferential clasps were studied. The clasps were fabricated with a 160 degree curvature around an 8-mm (diameter) cylinder and cast in Ticonium alloy. The clasps were subjected to 1500 cycles of 0.01 inch flexure. The degree of permanent deformation was not related to clasp form or width-thickness ratio. Of the five forms, only one exhibited no permanent deformation. According to Duncan's Multiple Range Test, significant differences in wear against a steel tooth model were observed among the five clasp forms evaluated (alpha = 0.05). PMID- 1520457 TI - Tensile stress in glass-ceramic crowns: effect of flaws and cement voids. AB - The objective of this study was to analyze the relative effect of loading site, occlusal thickness, ceramic flaws, elastic modulus of the cement, and voids in the cement layer on tensile stress that develops in molar glass-ceramic crowns under applied loads. Finite-element stress analyses were performed. Resin cement with a thickness of 0.05 mm was used. A central conical flaw (0.05 mm [diameter] x 0.05 mm) and a circular grooved flaw located under the cusp tips were included in all flaw cases. A void space confined within the occlusal region of the cement layer was also included in selected cases. For a ceramic thickness of 0.5 mm and a vertical distributed load applied at a distance of 1.3 mm from the vertical axis, the maximum tensile stresses were 100 MPa for a crown with flaws and a void, 87 MPa for a crown with no flaws and a void, and 75 MPa for a crown with flaws and no void. For a 1.5-mm-thick crown with flaws and a void, the tensile stress decreased to 22 MPa. When the load of 600 N was concentrated at the central point of the occlusal region, the peak tensile stress in a crown with flaws and no void was increased to 325 MPa. For the conditions analyzed in this study a large void in a flawed occlusal region of a thin molar crown (0.5 mm) is proposed as a mechanism of crown failure. PMID- 1520458 TI - Use of image analysis in determining masticatory efficiency in patients presenting for immediate dentures. AB - Image analysis was used to determine masticatory efficiency and performance before and after placement of immediate dentures. Sections of cored carrot were used as the test food and the particle size of chewed expectorated food was measured using image analysis. Measurements were shown to be accurate and reproducible. Masticatory function of immediate-denture patients was also compared with a similar number of dentate individuals and experienced complete denture wearers. Dentate subjects were significantly (P less than .01) more efficient at masticating the test food than were the complete- or immediate denture wearers. The new method of measurement removes the necessity for the unpleasant and unhygienic sieving process previously used in this type of study. PMID- 1520459 TI - Direct measurement of dimensional accuracy with three denture-processing techniques. AB - The Michigan Computer-Graphics Coordinate Measurement System (MCGCMS) was used to determine the dimensional accuracy of dentures processed by three different techniques: conventional heat compression, microwave, and visible-light activation. Standardized dentures were fabricated from casts made in an RTV silicone mold. All casts were duplicated with hydrocolloid and 42 dentures were made (ie, 14 dentures for each technique). The MCGCMS measured 22 points on two frontal planes to compare master casts to dentures. The results showed no significant difference in overall dimensional accuracy. At specific sites, however, the visible-light-activated technique produced significantly more flange distortion than did either the conventional or microwave techniques. PMID- 1520460 TI - In vitro bond strength of silica-coated metal posts in roots of teeth. AB - This study determined the in-vitro bond strength of abrasive-sprayed and silica coated Ni-Cr-Be posts to roots of extracted teeth using three resin cements (Panavia EX [P], Super-Bond C&B [SB], Prisma Universal Bond 2-Dicor [PUB-D]) and zinc phosphate cement (ZP). There were no significant differences among bond strengths of resin cements (8.8 to 10.8 MPa) bonded to abrasive-sprayed posts, but the bonds were stronger than those obtained using zinc phosphate cement (4.4 MPa). With the silica-coated posts, Super-Bond C&B produced the highest bond strength (14.5 MPa), followed by PUB-D (10.9 MPa), P (7.5 MPa), and ZP (5.4 MPa). PMID- 1520461 TI - A philosophy of dental practice. PMID- 1520462 TI - [Next of kin, our concern!]. PMID- 1520463 TI - [Hospital Walcheren--upside down world]. PMID- 1520464 TI - [The NIZW (Dutch Institute for Care and Welfare), or: how can we improve professional acting? Work development based in practice]. PMID- 1520466 TI - [The quality of reporting in the extramural care of COPD. Standards and criteria]. PMID- 1520465 TI - [Care of mentally retarded on Curacao]. PMID- 1520468 TI - [Learning and working, an opportunity gone by for a fruitful symbiosis]. PMID- 1520469 TI - [What do nurses do for pain?]. PMID- 1520467 TI - [After care of COPD by specialist community health nurses]. PMID- 1520470 TI - [Noorderhaven in Julianadorp--open doors]. PMID- 1520471 TI - [Work stress and autonomy]. PMID- 1520472 TI - [372 days--Werner update 10]. PMID- 1520473 TI - [What do you mean, an end to dare? Integrated nursing in a psychiatric residential facility]. PMID- 1520474 TI - [Good news about bad news. Psychosocial care concerning disclosure of diagnosis]. PMID- 1520475 TI - [The NIVEL (Dutch Institute for Research in Primary Health Care), or: primary care research. Focus on community care]. PMID- 1520476 TI - [Absenteeism is not intangible. Control of illness absenteeism by middle management]. PMID- 1520477 TI - [Scheperziekenhuis Emmen--building something better]. PMID- 1520479 TI - Scientists, institutions must confront misconduct in science properly, promptly. PMID- 1520478 TI - [Management in part-time--taboo?]. PMID- 1520480 TI - Survival, function, morphology and serological aspects of rat renal allografts. Effect of short-term treatment with cyclosporine A, anti-CD4 and anti-interleukin 2 receptor monoclonal antibodies. AB - The aim of this study was to investigate the effect of short-term treatment with cyclosporine A (CyA) combined with anti-CD4 (OX-38) and anti-interleukin-2 receptor (OX-39) monoclonal antibodies (MAbs) on graft survival, graft function, morphology, and anti-donor antibody levels in a BN-to-LEW rat kidney transplantation model. Spontaneous rejection occurred at 9.3 days (range 9-10 d). Administration of CyA (12.5 mg/kg/d) for 14 days prolonged graft survival to 33 days (range 23-40 d, P less than 0.02). Supplementing with OX-38 and OX-39 100 micrograms/kg/d, given i.p. from days 0 to 7, further prolonged graft survival to 70 days (range 38- greater than 100 d, P less than 0.02 vs controls and CyA group). One of seven recipients had good graft function for more than 100 days. A three-fold increase of the MAb dosage did not improve mean graft survival (53.5 d), but three of eight recipients had well functioning grafts for greater than 100 days. Kidney function was characterized by reduced creatinine clearance, also in the recipients with long-term graft survival, and a defect in concentrating urine creatinine with subsequent pronounced increase in urinary output. Graft histology showed a complex pattern of interstitial alterations including mononuclear cell infiltration, fibrosis, tubular atrophy and vascular damage with intimal/endothelial cell hyperplasia and perivascular inflammation. In nine of 10 MAb-treated recipients with graft survival greater than 60 days, granular deposits of immunoglobulins and C3 were found by immunofluorescence microscopy (IFM). The deposits were localized in the glomerular capillaries and mesangium. IFM in MAb-treated control animals could not demonstrate any deposits. Flow cytometric evaluation of posttransplant serum samples against donor target cells showed increasing amounts of anti-donor antibodies until the time of rejection, while recipients with long-term graft function had moderately positive cross matches up to two months after transplantation. Hereafter antibody titres decreased and cross-matches at the time of sacrifice were again negative. The morphological findings and the flow cytometric cross-match results seem to indicate a postponed antibody-mediated type of rejection. The reason why some kidney recipients showed decreasing antibody titres and stable long-term graft function is unclear. PMID- 1520481 TI - Increased expression of adhesion proteins (MAC-1) and altered metabolic response in human leukocytes exposed to surfactant in vitro. AB - In this study the modulatory effects of a well-defined surfactant preparation on blood leukocytes were investigated. The expression of the cell surface receptor MAC-1 was analyzed by flow cytofluorometry, and the metabolic response was measured by a chemiluminescence technique. An increase (p less than 0.05) in the MAC-1 receptor expression was observed in the granulocytes but not in the monocytes. There was a decrease in the metabolic response of the leukocytes after stimulation with phorbol myristate acetate (PMA) and a delay (p less than 0.01 for both) in the peak activity. Formyl-methionyl-leucyl-phenylalanine (fMLP) caused an increased peak (p less than 0.01). Thus, the surfactant preparation had a modulatory effect on blood leukocytes with regard to the expression of the cell surface receptor MAC-1 and the metabolic response. PMID- 1520482 TI - Peripolar cells and other granulated epithelial cells in renal biopsies. AB - The peripolar cell is a recently described glomerular epithelial cell which is situated within Bowman's capsule at the vascular pole. It contains cytoplasmic granules which contain plasma proteins, although it may also have a secretory function. The relationship between peripolar cells, other granulated glomerular epithelial cells and tubular epithelial cells is unclear. We have studied 242 biopsies from 19 types of renal disease for peripolar cells, other granulated epithelial cells and granulated tubular epithelial cells. Peripolar cells were most numerous in mesangioproliferative glomerulonephritis, IgA nephropathy, focal segmental glomerulosclerosis, membranous glomerulonephritis and lupus nephropathy. Other granulated glomerular epithelial cells were most prominent in diffuse lupus nephropathy, focal glomerulonephritis, acute vascular transplant rejection, crescentic glomerulonephritis and mesangioproliferative glomerulonephritis. Granulation of the tubular epithelium was most prominent in minimal change nephrotic syndrome and amyloidosis. It is likely that the granules in tubular epithelial cells represent lysosomes containing plasma proteins which have been absorbed from the tubular fluid. However, granulation of glomerular cells may represent a more specific response to glomerular damage. In addition, peripolar cells are prominent in only certain diseases, suggesting a specialized function. PMID- 1520483 TI - The prevalence of selective IgA deficiency in type 1 diabetes mellitus. AB - A significant increase in the prevalence of selective IgA deficiency has been observed in patients with autoimmune disorders such as systemic lupus erythematosus and rheumatoid arthritis. Insulin-dependent diabetes mellitus (IDDM) is an autoimmune disease and susceptibility to both IDDM and IgA deficiency is associated with HLA DQB1 alleles encoding non-Asp amino acids at position 57. In order to assess whether the prevalence of selective IgA deficiency is increased in IDDM, we have screened a homogeneous series of adult patients with IDDM for selective IgA deficiency. One patient (1:261) was found to have a selective IgA deficiency. The prevalence of selective IgA deficiency among adult French blood donors is 1:1400. Thus, although IDDM and selective IgA deficiency are both associated with the presence of non-Asp amino acids at position 57 of the HLA DQ beta chain, the frequency of this immunodeficiency in adult IDDM patients is not significantly increased. PMID- 1520484 TI - Expression of the epidermal growth factor receptor gene in human brain metastases. AB - Biopsy specimens of human brain metastases were examined for amplification and expression of the proto-oncogene c-erbB1 (located on chromosome 7) encoding the epidermal growth factor receptor (EGFR). Moreover, the tumour DNA was also examined for amplification of other cancer-related genes on this chromosome: the proto-oncogene c-met, the gene for platelet-derived growth factor A-chain, and the gene for plasminogen activator inhibitory type 1. All 18 brain metastases demonstrated positive binding of biotinylated EGF on cryosections. Three out of 18 metastases had amplification of the EGFR gene; the other chromosome-7 genes tested were not amplified. Thus, an increased EGFR gene expression seems to be a general finding in a wide range of carcinomas metastatic to the brain, whereas we found only occasional selective EGFR gene amplifications in single cases. PMID- 1520485 TI - Neonatal Proteus meningoencephalitis. Case report. AB - Proteus is an uncommon pathogen in neonatal meningitis and has, to our knowledge, not previously been described from Scandinavia. Our case illustrates the typical course of the disease when onset is within the first two weeks of life. The typical patient is a previously healthy, sometimes slightly preterm infant, who develops multiple brain abscesses and has a very poor prognosis. In cases with a later onset, factors predisposing for infection are common and the outcome is less severe. Our patient was a girl born at a gestational age of 36 full weeks, who was a little less alert than normal during the first three days and then became dramatically sick with convulsions and apnoeas. She died at the age of six days with severe brain damage. PMID- 1520486 TI - IgG subclass antibodies against Helicobacter pylori heat-stable antigens in normal persons and in dyspeptic patients. AB - Measurement of serum IgG antibodies against Helicobacter pylori seems to be useful in the diagnosis of H. pylori infections. IgG subclass antibodies against H. pylori have, however, not been investigated thoroughly. In this study IgG1, IgG2, IgG3 and IgG4 antibody levels against H. pylori were measured using an ELISA technique in 187 normal adult persons and in 174 patients with dyspeptic symptoms, of whom 99 patients were H. pylori positive. None of the IgG subclass antibody levels were better than the total IgG level for the diagnosis of H. pylori infection. The discrimination between H. pylori-positive and H. pylori negative patients was better with IgG1, IgG2 and IgG4 antibody levels than with IgG3 antibody level. IgG2 was the IgG subclass antibody that mainly contributed to the age-dependent increase in the IgG antibody level. This sustains the suspicion that cross-reactions between lipopolysaccharide (LPS) from H. pylori and LPS from other Gram-negative bacteria may occur. PMID- 1520487 TI - Experimentally induced ileal ulcers in rats. Formula diet is a preventive factor. AB - We recently described an experimental model in the rat to create recurring chronic ileal inflammation including ulceration. This model is dependent on an "in vivo culture" of normal intestinal contents. In the present experimental study we examined the effect of a polymeric and a hydrolyzed formula diet on the formation of ulcerating lesions using our rat model. Two groups of rats (twenty in each group) were fed either one of these formula diets eight weeks prior to the experimental procedure and this diet was continued until sacrifice eight weeks later. Twenty control rats also underwent the experimental procedure but were fed standard rat pellets for the same time periods. At sacrifice 60% of the control rats had developed ileal ulcers. None of the rats fed the formula diets developed macroscopic ileal inflammation or ulceration. The effectiveness of formula diets in inducing remission in Crohn's disease in humans may be linked to alterations in the intestinal microflora. We hypothesize that the formula diets in this experiment exerted a protective effect against ileal ulceration by altering the ileal microflora. Preliminary studies support this hypothesis but need to be expanded. PMID- 1520488 TI - Cell adhesion molecules as targets for unraveling the genetic regulation of airway inflammation. PMID- 1520489 TI - The relation between cell migration and activation in inflammation: beyond adherence. PMID- 1520490 TI - Synthetic surfactant (Exosurf) inhibits endotoxin-stimulated cytokine secretion by human alveolar macrophages. AB - Tumor necrosis factor-alpha (TNF), interleukin-1 beta (IL-1), interleukin-6 (IL 6), and interleukin-8 (IL-8) are inflammatory cytokines produced by alveolar macrophages (AMs) and implicated in sepsis-related adult respiratory distress syndrome (ARDS). Preliminary findings from clinical trials suggest that aerosolized delivery of the synthetic surfactant Exosurf (Burroughs Wellcome Co.) reduces mortality in patients with sepsis-induced ARDS. The purpose of the present study was to examine the effect of Exosurf on inflammatory cytokine secretion from AMs in vitro. AMs were obtained from normal nonsmoking adult volunteers. Secreted TNF, IL-1, IL-6, and IL-8 were measured by enzyme-linked immunoassays in 24 h culture fluids of AMs. Exosurf inhibited LPS-stimulated TNF, IL-1, and IL-6 secretion in a dose-dependent fashion. IL-8 secretion was not affected by Exosurf under these conditions. However, if AMs were preincubated for 24 h in media and then LPS-stimulated, IL-8 secretion was inhibited by Exosurf. Regulation of IL-8 production may differ from TNF, IL-1, and IL-6. Unstimulated cytokine secretion was not affected by any of the tested concentrations of Exosurf. The inhibitory effect of Exosurf on endotoxin-induced cytokine secretion by human AMs suggests that Exosurf may modulate inflammatory cytokine production in the lung. PMID- 1520491 TI - Polyamine transport and ornithine decarboxylase activity in hypoxic pulmonary artery smooth muscle cells. AB - Hypoxia causes remodeling of the pulmonary circulation that is dependent on increases in lungs polyamine contents. Mechanisms by which polyamines are regulated in hypoxic lung cells are unknown, but ornithine decarboxylase (ODC) activity, the initial enzyme in de novo biosynthesis, is depressed and polyamine transport is augmented in lungs from hypoxic rats (R.-T. Shiao et al. 1990. Am. J. Physiol. 259:L351-L358). To determine if hypoxia directly influences polyamine regulatory mechanisms in pulmonary vascular cells, we examined [14C]spermidine (SPD) transport and ODC activity in bovine main pulmonary artery smooth muscle cells (PASMCs) cultured under standard (culture medium Po2: greater than 100 mm Hg), "normoxic" (culture medium Po2: 50 to 70 mm Hg), or "hypoxic" (culture medium Po2: 18 to 30 mm Hg) conditions. Uptake of [14C]SPD in cells cultured under standard conditions was temperature- and concentration-dependent, exhibited saturation kinetics, and was abolished by metabolic inhibition. Modeling of transport according to Michaelis-Menten kinetics revealed that [14C]SPD uptake in cells cultured under standard conditions was characterized by Km and Vmax values of 0.78 microM and 4.5 pmol/min/10(6) cells, respectively. In comparison to cells cultured under standard conditions, Km was unaffected by culture under normoxic or hypoxic conditions while Vmax was increased to 18 pmol/min/10(6) cells in normoxic cells and to 33 pmol/min/10(6) cells in preparations cultured under hypoxic conditions. Inhibition of ODC with alpha-difluoromethylornithine (DFMO) also induced SPD transport, as evidenced by an increase in the Vmax to 65 pmol/min/10(6) cells. Both hypoxia- and DFMO-induced increases in [14C]SPD transport were suppressed by cycloheximide and actinomycin D, thus highlighting the importance of protein and RNA synthesis.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1520492 TI - Elevation of glutathione levels in bovine pulmonary artery endothelial cells by N acetylcysteine. AB - N-Acetylcysteine (NAC), a cysteine derivative with chemoprotective and radioprotective effects, was found to elevate bovine pulmonary artery endothelial cell (EC) glutathione after in vitro incubation. The elevation in glutathione was associated with enhanced uptake of radioactivity of cystine from the medium. Because cystine in medium was converted rapidly to cysteine and cysteinyl-NAC in the presence of NAC and given that cysteine has a higher affinity for uptake by EC than cystine, we conclude that the enhanced uptake of radioactivity was in the form of cysteine and at least part of the stimulatory effect of NAC on EC glutathione was due to a formation of cysteine by a mixed disulfide reaction of NAC with cystine similar to that previously reported for Chinese hamster ovarian cells (R. D. Issels et al. 1988. Biochem. Pharmacol. 37:881-888). However, NAC was more effective than cysteine in elevating cellular glutathione at equimolar concentrations, and at higher concentrations of NAC an elevation of EC glutathione occurred even in the absence of cystine in the medium through a currently unknown mechanism. Thus, at least two mechanisms are operative in the elevation of endothelial cellular glutathione by NAC. NAC may be a useful compound for elevating glutathione of the pulmonary vasculature for protection against oxidant stress. PMID- 1520493 TI - Hydrogen peroxide increases the availability of arachidonic acid for oxidative metabolism by inhibiting acylation into phospholipids in the alveolar macrophage. AB - Reactive oxygen species stimulate metabolism of arachidonic acid (AA) to eicosanoids in a variety of cells and tissues, yet the pathway(s) by which oxidants increase the availability of AA for oxidative metabolism are not known. Thus, we explored the effects of hydrogen peroxide (H2O2) on deacylation and reacylation of AA to determine the enzymatic mechanism(s) by which this oxidant increases levels of free, unesterified AA, and thereby its oxidative metabolism to eicosanoids, in the rat alveolar macrophage (AM). Over the range from 0.1 to 0.5 mM, H2O2 caused marked time- and dose-dependent inhibition of incorporation of [3H]AA into macrophage phospholipids, whereas calcium ionophore A23187 and zymosan particles did not cause such inhibition. Within this concentration range, there was an almost exact reciprocal correlation between inhibition of [3H]AA acylation and H2O2-stimulated accumulation of free [3H]AA in prelabeled AM cultures. Thimerosal, which blocks AA reacylation but spares deacylation via phospholipase A2 (PLA2), did not affect accumulation of free [3H]AA in prelabeled cells stimulated with H2O2, while markedly augmenting [3H]AA release in response to A23187 and to zymosan. Despite its ability to block AA acylation almost completely, H2O2 did not directly inhibit arachidonoyl CoA synthetase or arachidonoyl CoA:lysophosphatide acyltransferase, which catalyze AA incorporation into phospholipids. However, H2O2 (0.1 to 0.5 mM) markedly depleted AMs of ATP, required for synthesis of the acylation intermediate arachidonoyl CoA, suggesting that this was the means by which H2O2 inhibited acylation. Notably, H2O2 (0.03 to 3 mM) failed to stimulate macrophage PLA2 activity. We conclude that H2O2, in contrast to A23187 and zymosan, inhibits incorporation of AA into phospholipids, and that this represents the major mechanism by which the oxidant increases the availability of free AA for oxidative metabolism in the AM. This may be an important basis for release of eicosanoids in oxidant-induced inflammation and injury of the lung. PMID- 1520494 TI - Localization of surfactant-associated proteins SP-A and SP-B mRNA in rabbit fetal lung tissue by in situ hybridization. AB - Pulmonary surfactant is a lipoprotein substance, comprised of approximately 80% phospholipid and approximately 10% protein, that lowers surface tension at the air-alveolar aqueous interface. Surfactant is synthesized and secreted by alveolar type II epithelial cells where it is stored intracellularly in lamellar bodies. In the present study, we used the technique of in situ hybridization to localize the mRNA for two surfactant-associated proteins, SP-A and SP-B, in developing rabbit fetal lung tissue. We found that SP-A mRNA was first localized in rabbit fetal lung alveolar type II cells on day 26 of gestation, the time at which lamellar bodies are first observed within fetal lung type II cells. On day 28 of gestation, a very small amount of SP-A mRNA was also detectable in the epithelial cells of some bronchioles. In neonatal and adult rabbit lung tissue, SP-A mRNA was primarily restricted to alveolar type II cells; however, the epithelial cells of some bronchioles contained small amounts of SP-A mRNA. SP-B mRNA was first detected in cuboidal epithelial cells in the prealveolar region of the rabbit fetal lung tissue on day 24 of gestation, i.e., at least 2 days before the appearance of SP-A mRNA and lamellar bodies within differentiated alveolar type II cells. SP-B mRNA was detected in most bronchiolar epithelial cells of the rabbit fetal lung tissue at day 28 of gestation.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1520495 TI - Localization of muscarinic receptor subtype mRNAs in human lung. AB - m2 mRNA in airway smooth muscle; m3 mRNA in airway epithelium, airway smooth muscle, and submucosal glands. No detection of m4 and m5 mRNAs was observed in any cellular structures. The presence of various muscarinic receptor subtype mRNAs was confirmed by Northern blot analysis. Only human lung mRNA hybridized to the m1 probe giving a single 3.2 kb transcript. mRNA from the human cultured airway smooth muscle cells gave m2 and m3 hybridization bands of about 6.0 kb and 4.5 kb, respectively, while mRNA from the cultured airway epithelial cells gave only m3 hybridization band of 4.5 kb. With the exception of the airway epithelium, there was a good correlation between the distribution of mRNAs by in situ hybridization and the distribution of receptor subtypes by autoradiographic mapping. These results may have an important clinical implication, and also give rise to further investigation of gene regulation of pulmonary muscarinic receptor subtypes in health and disease. PMID- 1520496 TI - [Primary effect of carotid body stimulation on left ventricular inotropism in swine]. AB - The cardiovascular response to carotid body stimulation has been a interesting and simultaneously controversial subject. In fact, several authors described different responses depending on the animal species used (cat, dog, rabbit, monkey), time of stimulation (short-term v. long-term) and experimental conditions and procedures. According to our experience, the response to carotid body stimulation with cyanide, in normal breathing dogs, consists in hyperpnoea, bradycardia with arterial blood pressure fall (by means of longer diastolic periods), followed by a marked rise in arterial blood pressure and heart rate, after curarization. Concerning the inotropic response to carotid chemoreceptors stimulation, there exists some controversial and even antagonic opinions. In fact, some authors describe a positive inotropic effect, others a negative inotropic effect, and others still defend no inotropic response at all. In the present work, the authors try to contribute to the solution of this problem, studying a group of animals (pig) anaesthetised with chloralose, in which the major modulators of the inotropic response to carotid body stimulation (ventilation; heart rate; and ventricular load conditions) were controlled. To the evaluation of cardiac contractile state, indexes derived from the systolic isovolumic phase were used (maximum left ventricular pressure, dP/dtmax; dP/dtmin) in all the animals. In some animals, other indexes were also used (Vmax, Vpm, (dP/dt)/DP40, Tau and PB). The authors concluded that, in the present experimental conditions, the primary response to carotid body stimulation, in the pig, includes a positive inotropic effect. PMID- 1520497 TI - [Value of transesophageal echocardiography in the diagnosis of acute aortic dissection]. AB - We describe our experience of six patients with clinical suspicion of acute aortic dissection (AAD) who were studied consecutively by transesophageal echocardiography (TEE) from April to July of 1991. All of them were previously submitted to transthoracic echocardiogram. The diagnosis was correctly established by TEE in five cases, confirmed by aortography and/or surgery (four cases), or by autopsy (one case). In one patient the diagnosis of AAD was excluded by TEE, and posteriorly by nuclear magnetic resonance. Four patients had a Stanford type A, and one patient a type B dissection. The site of entry was identified in three cases; the intimal entry tear of the type B dissection, not observed by TEE, was localized in the aortic arch by aortography. In three of the four type A dissection cases, a thrombus in the false lumen and an aortic regurgitation were found. No other noninvasive methods were used after the diagnosis of AAD by TEE. The surgical repair was successful in three cases, one of which, without previous necessity of aortography. In our experience, TEE increased extraordinarily the diagnosis efficacy of AAD, making possible an earlier therapeutic approach, and probably contributing to the improvement of the prognosis of this pathology. PMID- 1520499 TI - [Specifying for the general physician. Digitalis therapy in elderly patients]. AB - The experimental and clinical evidence on the decreased efficacy of digitalis on old age are reviewed. The trials on the efficacy of digitalis on elderly in heart failure and sinus rythm, are analysed and we try to characterize the sub-group of responders. So we try to explain the criteria to choose the therapeutic dose, to avoid intoxication and to interpret the seric concentrations. We describe the pharmacocynetics of digitalis on old people on heart failure which can explain the susceptibility to intoxication. We reviewed the incidence of digitalis intoxication on old age and the difficulties on its recognition. PMID- 1520498 TI - [Influence of the use of Swan-Ganz catheter on the mortality from acute myocardial infarction]. AB - OBJECTIVE: to evaluate the statistical significance of the haemodynamic examination making use of the Swan-Ganz catheter (S-G) on the hospitalary mortality of patients (pts) with acute myocardial infarction (AMI). CONCEPTION: Not randomized, not controlled and retrospective study. SETTING: Intensive coronary care unit (CCU). PATIENTS: 2562 pts with AMI sequentially admitted to a CCU were studied. METHODS: The 2562 pts were divided in two groups: Group A- involving 2117 pts not submitted to haemodynamic examination; Group B-constituted by 445 pts (17% of all pts) submitted to haemodynamic examination. All pts admitted to the study were distributed according to the four classes of Killip. The pts included in each Killip class were distributed by the groups A (not catheterized) and B (catheterized). Hospitalary mortalities of the pts included in the global A and B groups, and the mortalities of the patients included in the particular A and B groups in each Killip class were determined. To evaluate the statistical significance of the differences in distributions of the number of pts who survived and who died in each set of A and B groups square chi test was used. Values of p less than 0.05 were considered as statistical significant. RESULTS: The distributions of the pts who died and who survived during the stay in the hospital by the A and B groups, be it in the total group of patients be it in each Killip class, were not significant different (p greater than 0.05). CONCLUSIONS: The mortalities of pts with AMI submitted or not to haemodynamic examination with S-G catheter did not significantly differ even in each Killip class, which means that it was not demonstrated a benefit with the S-G catheter use in the pts with AMI. In the presence of this conclusion and considering that retrospective studies must be interpreted with circumspection, it seems necessary to accomplish a prospective randomized and controlled study for evaluation the risk/benefit relation of the haemodynamic examination with the S-G catheter in pts with AMI. PMID- 1520500 TI - [Anomalous origin of the left coronary from the pulmonary artery in adults: diagnosis with bidimensional, pulsed and color Doppler echocardiography]. AB - Anomalous origin of the left coronary artery (LCA) from the pulmonary trunk (PT) is an uncommon but frequently lethal congenital lesion of infancy. Clinically it may be difficult to distinguish from congestive cardiomyopathy, and the diagnosis is usually made by angiography. We describe the case of a 38 years old woman, in whom identification of this anomaly was achieved by 2D-Echo, pulsed Doppler and color flow mapping. She complained of fatigue, effort dyspnea and atypical chest pain. A II/VI systolic murmur at left sternal border was heard. There was cardiac enlargement on chest X-ray and ECG was suggestive of an old anterolateral myocardial infarction. The 2D-Echo study showed a dilated, poorly contracting left ventricle. A prominent right coronary ostium was recorded, but the LCA ostium could not be visualized. There was retrograde diastolic and systolic flow in proximal PT, where an anomalous vessel was seen in continuity with it by color flow mapping. Cardiac catheterization confirmed the diagnosis. The patient underwent successful reimplantation of the anomalous LCA, from the PT to the aorta. This case demonstrates usefulness of Echocardiography in the assessment of coronary artery anomalies. PMID- 1520501 TI - [Ventilation in intensive care units]. AB - In this article the author intends to make a review of the most important indications and aims of mechanical ventilation, and the repercussion of artificial ventilation over the different systems of the body. The main kinds of ventilators used for the management of the critically ill patient, connected to a ventilator are reviewed. PMID- 1520502 TI - Cardiac function and Fourier phase data from simulated Wolff-Parkinson-White syndrome in a baboon model. AB - The diagnostic value of Fourier phase analysis and planar scintigraphy in Wolff Parkinson-White (WPW) syndrome has been suspect. This study investigates phase analytical data from planar radionuclide ventriculography of six baboons with simulated WPW syndrome by means of implanted electrodes. An electrode in the atrium controlled the heart rate and a subsequent stimulation was delivered by electrodes placed at different sites on the ventricles, delayed to cause the characteristic delta wave of the WPW syndrome. Sensitivity for accurately localizing variously-situated first points of activation (FPAs) from the Fourier phase images was found highest for premature right ventricular (RV) activation, and for atrioventricular (AV) delays around 125 msec. Other sites were subject to artifacts. Changes in cardiac function, phase delay, and histogram parameters were not statistically meaningful. PMID- 1520503 TI - Tumor and organ biochemical profiles determined in vivo following uptake of a combination of radiolabeled substrates: potential applications for PET. AB - This paper describes a method which generates an in vivo metabolic profile of tumors and organ tissues derived from the tissue uptake of a combination of radiotracers. Metabolic substrates labeled with carbon-11, a positron-emitting radionuclide (T1/2 = 20.4 min) have been used to probe tumor metabolism in vivo using positron emission tomography (PET). Carbon-11 labeled radiotracers which have been used include alpha-aminoisobutyric acid (AIB), 2-deoxy-D-glucose (2 DG), and thymidine (TdR). This paper reports data on the tissue distribution of carbon-14 labeled analogues of AIB, 2-DG, and TdR. Tissue distribution studies were carried out in normal male Copenhagen rats, in rats bearing Dunning R3327G or R3327H prostatic adenocarcinomas, and in tumor rats that have been treated with difluoromethylornithine and methylglyoxal-bisguanylhydrazone, or with diethylstilbestrol. A combination of the tissue distribution data of these radiolabeled agents is used to provide a metabolic description of the state of a tumor or tissue in vivo. This approach to defining a tissue's biochemical profile may be useful for the assessment and prediction of a therapeutic response, even at low tracer concentrations in a tumor, and may be useful in relating the biochemical characteristics of one tissue to that of another. PMID- 1520504 TI - Detecting coronary artery disease using SPECT imaging: a comparison of thallium 201 and teboroxime. AB - Thirty subjects underwent single photon emission computed tomography (SPECT) imaging with technetium-99m teboroxime (TEBO). Of these, 26 underwent thallium SPECT imaging and 25 underwent quantitative coronary arteriography (QCA). Twenty one of the subjects underwent all three studies. SPECT images were reviewed by two independent observers blinded to the clinical data. Stenoses were considered significant if there was a greater than or equal to 50% diameter narrowing as defined by QCA analysis of the coronary arteriograms. The overall sensitivity and specificity was 78% and 78%, respectively, for thallium-201. The overall sensitivity and specificity for teboroxime was 72% and 80%, respectively. The results obtained for these two tracers were not statistically different. Some of the false-positive results obtained from teboroxime imaging appear to have been due to the 10-min acquisition protocol and can be reduced with the use of new software programs using a continuous 3-min acquisition and dipyridamole. Teboroxime's rapid biologic half-life allows completion of SPECT imaging within 60-90 min, compared with the minimum of 4 h required for thallium SPECT imaging. PMID- 1520505 TI - Application of Hilbert transform to radionuclide-gated cardiac studies: analysis of asynchronous emptying and filling in various heart diseases. AB - Fourier phase analysis has generally been used to investigate asynchronous emptying and filling in various heart diseases. A potential limitation of this form of analysis is curve fitting error, since a truncated Fourier series may not adequately describe the shape of a time-volume curve (TVC) and thus may produce errors in indices calculated from the fit. To overcome this problem, we developed a new method using Hilbert transform. Using Hilbert transform, the instantaneous phase (IP) curve was calculated directly from the TVC obtained from multigated cardiac blood pool images. Four parameters [time to maximum IP [T(max)], time to 0 in IP[T(0)], time to minimum IP[T(min)], and time from 0 to minimum IP [T(min 0)]] were extracted from the IP curves for each pixel, and functional images were constructed in 40 patients with ischemic heart disease (IHD), 16 with hypertrophic cardiomyopathy (HCM), 3 with dilated cardiomyopathy (DCM), and 7 normal controls (N). The standard deviations (SD) of these parameters were then calculated for the left ventricle. In IHD patients with a left ventricle ejection fraction (LVEF) of less than 50% and in DCM, the SDs of all parameters were significantly higher than in group N. In IHD patients with an LVEF of greater than 50%, the SDs of T(min), T(0), and T(min-0) were significantly higher than in group N, but there was no significant difference in the SD of T(max). In HCM patients, the SDs of T(min) and T(min-0) were significantly higher than in group N, suggesting the presence of asynchronous filling. In conclusion, this method appears to be promising for the quantitative analysis of asynchronous emptying and filling in various heart diseases. PMID- 1520506 TI - Dynamic human glycogen and glucose metabolism detection utilizing in vivo 13C NMR. AB - The dynamic detection studies of glucose-glycogen metabolism of the human liver were performed with normal volunteers. A single tuned surface coil of 20-cm diameter was used for 13C (at 16.04 MHz). Natural glucose 100 g was administered for the natural abundance 13C MR dynamic study and 13C enriched (99%) 1-13C-D glucose 1 g mixed 75 g glucose was administered to study the 13C enrichment effect. The total scan time of this dynamic study was 1 hr and each single scan time was 20 min. We did not use proton decoupling for the human 13C MR study. Localized (PRIME) proton shimming was performed and the shim value was less than 20 Hz. Glucose and glycogen spectra were clearly visible at 120 to 80 ppm and about 3 hr later both peaks almost disappeared. These data demonstrate that dynamic hepatic glucose-glycogen metabolism should be possible to detect which should allow for the direct diagnosis of hepatic glucose-glycogen metabolic disorders. PMID- 1520507 TI - [Development of sound lateralization]. AB - Perceptual sound lateralization is determined from differences in time and loudness of signals arriving separately at bilateral ears, with the time difference being the more important one. The author examined the development of sound lateralization using a self-recording device developed by Sato T, which measures the sensitivity of sound lateralization on the basis of time and loudness differences separately. Subjects were 59 children aged 2 to 18 years and 12 adults who were audiologically and neurologically normal. Sound stimulus was 500 Hz continuous band noise. (1) The testable rate was increased in children older than the age of 4, and all children over 7 years of age could be tested. (2) Children over 4 years of age could lateralize sound on the basis of time difference. Sensitivity to time differences improved rapidly, showing a steep curve, in children from the ages of 4 to 6, and then increased slowly until adulthood. (3) Sensitivity to loudness differences increased and the normal range distribution decreased with age. There is a possibility that children aged 4 can discriminate loudness difference almost as well as adults. PMID- 1520508 TI - [Development of human cerebellar granular layer: a morphometric study]. AB - Development of the cerebellar granular layer, the external granular layer (EGL) and the internal granular layer (IGL), was studied morphologically to make complete serial sections of the brain from human fetuses ranging 12 to 40 weeks' gestation (WG). To examine the chronological changes and the regional differences, we measured the thickness of the layer microscopically among five different parts of the cerebellum: anterior lobe/hemisphere (AH), anterior lobe/vermis (AV), posterior lobe/hemisphere (PH), posterior lobe/vermis (PV) and flocculus (FL). EGL was the most superficial layer composed of densely packed undifferentiated cells. Its thickness showed little changes during the fetal period of 12-40 WG for all parts except FL where EGL was thicker than those in other parts and made a gradual attenuation with development. We noticed at least three stages in the fetal development of IGL: 1) the primary or undifferentiated stage (before 18 WG) when IGL was hardly distinguishable from the layer of immature Purkinje cells (PCL); 2) the secondary or intermediate stage (18 to 30 or 35 WG) when it was clearly visible and almost stable in thickness for all parts; 3) the tertiary or developing stage (30 or 35 to 40 WG) when it showed a dramatic increase in thickness as the formation of cerebellar folia was proceeding. During the intermediate stage the Lamina dissecans was observed between PCL and IGL typically in PH. Regional differences were detected in a period of transition from the intermediate to the developing stage among each part: the developing stage appeared earliest in AV and FL and latest in PH.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1520509 TI - [Time-course changes of regional cerebral blood flow by SPECT with N-isopropyl-p [123I]-iodoamphetamine in childhood partial seizures]. AB - Single photon emission computed tomography (SPECT) with N-isopropyl-p-[123I] iodoamphetamine was performed twice at different times in 18 children suffering from partial seizures to evaluate the time-course changes of the hemodynamics in the focal region. Comparison of the 2 SPECT images revealed that a decreased regional cerebral blood flow (CBF) in the first was normalized in 4 cases (22.2%) and contracted in 7 cases (38.9%). The region of decreased blood flow in the second was contralateral to that in the first in 1 case (5.6%) and unchanged in 6 cases (33.3%). Most of the normalized and contracted cases were those in which clinical seizures disappeared and the EEG findings were normalized. In these cases which responded to treatment, the decreased regional CBF was also found to be improved. Repeated SPECT appears to be useful for evaluating the therapeutic efficacy. On the other hand, most of the unchanged cases were those in which clinical seizures were frequent or uncontrolled, or which persistently showed the abnormalities in their EEG. SPECT was considered to reflect well the conditions of the epileptic foci. These results indicate that repeated SPECT for observing the time-course changes of the regional CBF represents a useful technique with can be applied in evaluating the therapeutic efficacy or deciding the time to discontinue treatment and for pathogenetic elucidation of the epileptic foci. PMID- 1520510 TI - [A biochemical study of an animal model with defective muscle glycolysis, induced by iodoacetate administration]. AB - A rat model produced by intraaortic injection of sodium iodoacetate was analyzed biochemically. Hind leg muscles obtained from iodoacetate-injected site showed a selective inhibition of the glyceraldehyde-3-phosphate dehydrogenase (G3PD) activity less than 10% of control mean. No loss of mitochondrial enzyme activity was observed. Electrical stimulation at the sciatic nerve revealed muscle contractures and this muscle showed a mild degeneration in histochemically. This study indicates that this model will be useful to study the pathophysiology of human muscle glycogen storage diseases. PMID- 1520511 TI - [A case of cervical myelopathy due to atlanto-axial subluxation with athetoid cerebral palsy]. AB - We reported cervical myelopathy due to atlanto-axial subluxation of athetoid quadriplegia of cerebral palsy. This lesion was present from upper cervix to lower medulla oblongata, and appeared on MRI. The changes of sSEP was useful to evaluate his spinal function. We think that pediatricians need to understand this pathophysiology, particularly for multihandicapped children. PMID- 1520512 TI - [An autopsy case of Fahr disease (infantile form)]. AB - A 13-year-old girl with Fahr disease (infantile form) was reported. Her parents were consanguineous. Her elder sister had mental retardation and spasticity of the lower limbs, and died at 23 years of age. The patient suffered from infantile spasms at 3 month. She was bed-ridden, nonverbal, microcephalic and blind. Cranial CT revealed massive calcifications in the basal ganglia, periventricular white matter, dentate nucleus and cerebellar white matter. EEG showed a suppression-burst pattern. At 13 years, she died of pneumonia and hyperammonemia. Microscopic examination of brain showed perivascular non-arteriosclerotic ferro calcinosis. The periventricular granules are 1-4 mu or 12 mu in diameter. This pathological change was observed only in the central nervous system above midbrain. No calcifications were found in the pituitary and the vessels of pia mater. Also a reduced ornithine transcarbamylase activity was found in the liver, which was probably not related with cerebral calcifications. Infantile form of Fahr disease is rare and may be heterogeneous in etiology. However, clinical manifestations and pathological findings were similar to those in previous reports of Fahr disease in childhood. It is one of the disorders causing infantile spasms. PMID- 1520513 TI - [A case of childhood epilepsy with occipital paroxysms (CEOP) presenting particular EEG findings]. AB - We reported a case of an eight-year-old boy with CEOP. His parents and sibling were in good health. There was no family history of epileptic and neurological disease. He had his first attack of unconsciousness with fixation of eye movement for a few minutes at the age of 7 years. After six months, he experienced attacks of vomiting followed by loss of consciousness and elementary visual hallucinations consisting of red and blue colors. Sometimes he complained of contraction of visual field for 10 to 20 seconds, as if a curtain had fallen following the visual hallucination of a bright light spot. At the age of eight years, he was admitted to our hospital for evaluation and therapy. Investigations included neurological examination, IQ, CT findings were normal. Visual evoked potential revealed more reduced amplitude in the left side than in the right. The EEG findings during the waking state showed continuous bilateral 1-2 c/s spike and wave complex discharges in occipital and posterior temporal areas. These discharges were immediately suppressed by eyes-opening in an illuminated room, but not in a dark room. However, during the light sleep stage, diffuse irregular spike and wave discharges appeared frequently with left side dominance. From the clinico-electrophysiological findings we diagnosed him as CEOP. In order to investigate the changes of the occipital spike and wave discharges by photic stimulation, we administered intermittent photic stimulation (IPS) for 10 seconds at each frequency between 1-30 flashes/sec (f/s) in a dark room.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1520514 TI - [A case of acute encephalopathy with symmetrical low density areas in the thalami on CT; serial CT and MRI findings]. AB - A 5-year-old girl was admitted to our hospital because of fever, vomiting, diarrhea, convulsion and disturbance of consciousness. She was diagnosed as having acute encephalopathy, which is characterized by the symmetrical low density area in the thalami on CT. Serial MRI findings revealed the bleeding with edema in the thalami, and multifocal lesions with prolonged T1 and T2 relaxation time in the acute phase of the illness. Multifocal lesions were no longer found two months later. The sequential changes on the images about the bleeding in the thalami were not confirmed by simultaneous CT scans. The findings of the bleeding in the thalamic lesion are consistent with those of an autopsy report previously described and indicate the vascular involvement in the thalami in acute encephalopathy, which is characterized by the symmetrical thalamic lesions with the characteristic finding of low density on CT scans. PMID- 1520515 TI - [MRI findings of moyamoya disease in children]. AB - Magnetic resonance imaging (MRI) findings were evaluated in two cases with moyamoya disease. A twelve-year-old girl and a five-year-old boy were admitted to our hospital with the complaints of transient ischemic attack. They were diagnosed as having moyamoya disease by cerebral angiogram. MRI clearly presented cerebral infarction by T2-weighted imaging and multiple small round or tortuous hypo_signal areas around the basal ganglia by proton density weighted imaging. These findings were consistent with moyamoya vessels shown by cerebral angiogram. Moyamoya vessels were visualized more clearly on proton density weighted imaging than on T1-weighted imaging. MRI is less invasive than cerebral angiogram and repeated safely. It might play an important role in a follow-up study of morphological changes on moyamoya vessels. PMID- 1520516 TI - [Orbicularis oculi electromyogram in a girl with ocular myasthenia gravis]. AB - A 12-month-old girl with ocular myasthenia gravis was reported. Electromyograms (EMG) of the orbicularis oculi muscle were studied during a period of 16 months. The degree of the waning phenomenon on EMG correlated well with that of her clinical symptoms. The study of post-tetanic exhaustion after repetitive electrical stimulation at 20 Hz for 4 seconds, was the most sensitive technique in the evaluation of the function of neuromuscular junction. EMG showed the waning phenomenon in the initial worsening after a high dose methylprednisolone therapy, and at the symptom-free stage without medication after the steroid therapy. In our patient, orbicularis oculi EMG was useful in the estimation of the severity of ocular myasthenia gravis and the effect of its treatment. PMID- 1520517 TI - [Moyamoya disease manifested by recurrent torticollis]. PMID- 1520519 TI - [A case report--complete remission of myasthenia gravis after measles]. PMID- 1520518 TI - [Magnetic resonance imaging and spectroscopy of Pearson syndrome]. PMID- 1520520 TI - [Progressive hemifacial atrophy (Parry-Romberg syndrome)]. PMID- 1520521 TI - Carbohydrates in oral epithelia and secretions: variation with cellular differentiation. AB - The oral mucosa has been extensively studied in the past, and has thus become a model for demonstration of dynamic changes in cellular glycosylation and many other cell products such as keratins in relation to epithelial differentiation. The extensive knowledge of the glycosylation pattern in normal cells is instrumental in evaluation of the often occurring aberrant glycosylation of carcinoma cells. The emerging developments in antibodies to the glycosyltransferases and probes for their genes will enable us to gain insight into the regulatory mechanisms leading to the apparently well-controlled glycosylation process in epithelia. The first example of such a correlation has been studied in oral epithelia. PMID- 1520522 TI - Carbohydrate changes in squamous cell carcinomas. AB - Cell surface carbohydrates serve as differentiation and development markers characteristic of different cell and tissue types. The expression of these carbohydrate antigens is often significantly altered in tumours, particularly in those arising from epithelial tissues. Analyses of cell surface carbohydrates in stratified epithelium have shown a remarkable variation in glycosylation pattern in relation to terminal differentiation. The carbohydrate expression is altered in squamous cell carcinomas and in premalignant lesions. There is evidence that the expression of certain carbohydrate structures in the deep invasive part of the tumours is correlated with tumour prognosis. The change in carbohydrate expression can at present be explained by the lack of synthesis of specific glycosyltransferases. New evidence suggests that the expression of certain carbohydrate structures may be importance for the formation of metastasies. PMID- 1520523 TI - Changes in the glycosylation pattern of histo-blood group antigens in benign, premalignant and malignant laryngeal epithelial lesions. AB - The glycosylation of epithelial cell surface antigens is an indicator of cellular differentiation, and changes in the pattern of expression are seen in different premalignant and malignant epithelial lesions. The purpose of this investigation was to study alterations in the sequential build-up of carbohydrate structures during development of malignancy in laryngeal epithelial lesions. Sixteen routinely processed biopsies showing grave dysplasia/carcinoma in situ were examined. All patients were observed without treatment until malignancy could be affirmed. Five of the patients normalized their laryngeal mucosa spontaneously during observation, whereas 11 progressed invasive carcinoma. Biopsies from normal, hyperplastic and carcinomatous laryngeal epithelium were used as controls. Six monoclonal antibodies (MAbs) related to the ABO- and the TTn blood group systems were used for demonstration of carbohydrate antigens by an indirect immunofluorescent staining method. Benign lesions had a normal sequence of glycosylation. Dysplasias showed accumulation of shorter chains in superficial layers, usually with a patchy dispersion. It is possible by carbohydrate distribution to objectively establish the diagnosis of grave dysplasias/carcinoma in situ, and on the basis of carbohydrate distribution we can divide the lesions into subgroups which are of prognostic relevance. PMID- 1520524 TI - Carbohydrate antigens in human lung carcinomas. AB - Lung carcinomas represent a heterogeneous group of tumours with large variations in the biochemical, clinical, morphological and pathological manifestations. Despite the neuroendocrine features of small cell lung cancer (SCLC), it is today generally accepted that all types of lung cancer emanate from a common endodermally derived multipotent stem cell of the bronchial epithelium. NCAM (neutral cell adhesion molecule) has been shown to be a sensitive marker of SCLC. The presence of NCAM, with the alpha (2,8) polysialic acid units characteristic of embryonal NCAM, in SCLC and in a portion of NSCLC, seems to correlate with the malignant behaviour and prognosis of the tumours, suggesting that NCAM may have a functional role in the clinicopathological manifestations of lung cancer. Fuc-GM1 with 2-hydroxy fatty acids as a characteristic component of the ceramide has been found to be a unique ganglioside of SCLC, detected in the tissues as well as in serum from SCLC patients using specific monoclonal antibodies. Accumulation of sialylated and fucosylated polylactosamine type 2 carbohydrate glycolipid and glycoprotein antigens was found in serum and tissues of lung tumours in accordance with what is described in gastrointestinal carcinomas, and these antigens may be regarded as general carcinoma antigens irrespective of organ. Sialylated and fucosylated type 1 antigens, and gangliosides with NeuAc alpha (2,6)Gal linkage were also accumulated in lung cancer. The human immune system has been found to recognize lung cancer carbohydrate antigens, which might be human lung cancer autoantigens. PMID- 1520525 TI - Simple mucin-type carbohydrate antigens (Tn, sialosyl-Tn and T) in gastric mucosa, carcinomas and metastases. AB - Immunohistochemical study of the expression of simple mucin-type carbohydrate antigens (Tn, sialosyl-Tn, T and sialosyl-T) was performed using specific monoclonal antibodies in the mucosa adjacent to gastric carcinomas histologically appearing unaffected (n = 58), and in primary gastric carcinomas (n = 87) and their metastases (329 lymph nodes and two liver metastases). Normal-looking mucosas: Tn antigen expression was identified in all the cases; sialosyl-Tn in eight cases; T antigen was never expressed and sialosyl-T antigen was observed in four cases; the expression of these antigens was distinctly limited to the cytoplasm, mostly in the supranuclear (Golgi) area. All the mucosas with intestinal metaplasia showed sialosyl-Tn expression in the goblet cells. Gastric carcinomas: 80 cases (91.9%) stained for Tn antigen, 69 cases (19.3%) expressed sialosyl-Tn antigen, 18 cases (20.7%) expressed T antigen and 17 cases (19.5%) stained for sialosyl-T antigen. In contrast to normal mucosa, carcinoma cells expressed simple mucin-type antigens both at the cytoplasm and at the cell membrane. Most primary carcinomas were concurrently stained for Tn and sialosyl Tn antigens alone (41.1%), or together with T antigen or sialosyl-T antigen (28.7%). We found a close relationship between the expression of simple mucin type carbohydrate antigens in the primary tumours and their respective metastases. T antigen (and sialosyl-T antigen) expression was correlated with the wall invasiveness of the tumours. The 18 tumours expressing T antigen and 16 out of the 17 tumours expressing sialosyl-T antigen had nodal metastases and/or sialosyl-Tn expression and the aggressiveness of the tumours (wall penetration, lymph node metastasis and venous invasion). No significant differences were observed between positive and negative tumours for Tn, sialosyl-Tn, T and sialosyl-T antigens regarding the morphologic at type, growth pattern, ploidy or lymphoid infiltrate of the primary tumours. PMID- 1520526 TI - Basic biochemistry of cell surface carbohydrates and aspects of the tissue distribution of histo-blood group ABH and related glycosphingolipids. AB - Cell surface carbohydrates may be protein- or lipid-linked. The structural polymorphism of the oligosaccharide chains is extensive due to variations in monosaccharide composition, carbohydrate sequence, branching, linkage position and linkage anomericity. Blood group ABH and related glycosphingolipids show a remarkable tissue-specific expression with possible implications in areas such as transfusion medicine, transplantation surgery and oncology. This communication gives a condensed description of the present knowledge of the tissue-specific distribution of histo-blood glycolipids in humans. PMID- 1520527 TI - Carbohydrate changes in bladder carcinomas. AB - The cloning of glycosyltransferases is a major breakthrough in the study of glycosylation in normal an malignant tissue. In bladder tumours we need a molecular explanation for the changes observed in especially Gal alpha 1-3 and GalNac alpha 1-3 transferase activity. Studies of the events (transcription/translation) taking place in the different cell layers would also be of importance, especially if the cells could be sorted layer by layer. The urine is a source of malignant cells, and could be a target for diagnosis as well as monitoring. Studies of urinary tumour-associated glycoconjugates or tumour associated rearrangements in glycosyltransferase genes in exfoliated cells would be of great interest. PMID- 1520529 TI - Carbohydrate pathology. PMID- 1520528 TI - Genetic regulation of the expression of ABH and Lewis antigens in tissues. AB - Sequential appearance of ABH antigens in different animal species shows a progression from tissues of endodermal to ectodermal and finally mesodermal origin, human erythrocytes being the last cells to acquire these antigens. In view of this, ABH antigens should be called tissue or histo-blood group antigens rather than blood group antigens. In addition to the glycosyltransferases encoded by the ABO genes, several alpha-2, alpha-3 and alpha-4-fucosyltransferases are needed to account for the known ABH histo-blood group antigens. The genetic polymorphism of the genes encoding each of these enzymes defines inter-individual differences. In addition, in the same individual various tissues express these antigens in a different way. For each adult epithelial tissue, antigenic expression is related to cell maturation from germinal layer to surface epithelium. Differential expression is also found at various embryonal stages of the same cells. Examples of these phenomena are presented in an effort to gain further insight into the genetic regulation of the expression of these complex oligosaccharide molecules. PMID- 1520530 TI - Carbohydrates of the cell surface: molecular aspects of glycosyltransferases and their genes. AB - With the development of monospecific antibodies to transferase proteins as well as cDNA probes to cloned transferase genes, the study of glycosylation and its regulatory mechanisms holds great promise for the future. Here we provide a brief overview of the present knowledge of glycosyltransferases, their primary structure, cellular topography, regulation, and the basis of the genetic polymorphisms as revealed by blood groups. PMID- 1520531 TI - Carbohydrates of human immunodeficiency virus. AB - Elucidation of the mechanism by which viral infection induces the appearance of carbohydrate neoantigens is highly important. Results from such studies could be expected to be significant for a general understanding of the regulation of glycosylation, and perhaps especially important for the understanding of glycosylation in cancer. For anti-viral therapy in AIDS, inhibitors of glycosylation enzymes are very promising as their mode of action may preclude evolvement of resistent HIV substrains, which seems to be a common problem with the reverse transcriptase inhibitors presently used. Successful therapy with glycosylation enzyme inhibitors will, however, require the development of more specific and less toxic compounds. If carbohydrate antigens can elicit a neutralizing immune response in vivo, the possibility exists that carbohydrate neoantigens can be utilized in the construction of a vaccine against AIDS. PMID- 1520532 TI - Specificity of an oligonucleotide primer pair and of a single-base substitution in the amplification and detection of env gene sequences of HTLV-I variants from Papua New Guinea and the Solomon Islands. PMID- 1520533 TI - Nucleotide sequence analysis of an HTLV-I isolate from a Chilean patient with HAM/TSP. AB - Isolates of HTLV-I have been characterized from a number of different regions of the world; however, there has not been a nucleotide sequence analysis of an HTLV I isolate from a South American country. Reported here is an individual from Chile identified with the HTLV-I-associated neurological disease HAM/TSP. The sera and the nucleic acid sequence of the HTLV-I present in peripheral blood lymphocytes from this Chilean HAM/TSP patient over a two year period are characterized. During this time, the patient's condition grew progressively worse. While the serological profile of this patient was unremarkable in comparison with other HAM/TSP patients previously described, nucleic acid sequence analysis identified two nucleotide positions which contained nucleotides unique to this Chilean isolate. The nucleotide sequence analysis also indicates that the Chilean HTLV-I isolate is more closely related to Caribbean and Japanese isolates of HTLV-I than to the African and U.S. isolates described so far. PMID- 1520534 TI - Establishment of T-lymphoid cell lines from Morroccan patients with tropical spastic paraparesis. AB - Two T-cell lines were established from peripheral blood mononuclear cells of two Moroccan patients with tropical spastic paraparesis and then named PR52 and PR144. The two cell lines showed a T lineage of activated CD4+ with high density of Tac+ (IL2 receptor). No expression of CD8 was observed. The virus particles were detected by reverse transcriptase activity and the viral antigens were also detected by immunofluorescence (IF) and Western blot. After six months of culture greater than 90% of the cells exhibited HTLVI antigen by IF. Lysate virus particles on Western blot analysis revealed p19,p24, and p53 gag protein similar to those detected in C91/PL virus particles from an adult T-cell leukemia (ATL) patient. gp46 and gp61 were also weakly detected. These two T-cell lines established will serve as substrate for further comparative studies on TSP and ATL isolates. PMID- 1520535 TI - Anti-human immunodeficiency virus effects of zidovudine in combination with double-stranded RNA poly I poly C in T cells and monocytes-macrophages. AB - A comparison of the activity against human immunodeficiency virus 1 of zidovudine (AZT) and poly I poly C double-stranded RNA both alone and in combination in MT4 cells and primary monocyte/macrophage (M/M) cultures was made. The inhibition of the HIV-induced cytopathic effect or reverse transcriptase production by AZT in MT4 cells was not modified by the combination of the two agents. In contrast, AZT inhibition of reverse transcriptase production in the supernatant of M/M cultures was enhanced by the addition of poly I poly C. The inhibitory effect of the drug combination was more marked in M/M than in MT4 cells, indicating that the evaluation of compounds involving the induction of an antiviral state should be tested not only CD4+ T cells but also in monocyte-macrophages. PMID- 1520536 TI - Loss of synergistic response to combinations containing AZT in AZT-resistant HIV 1. AB - The use of combination chemotherapy for the treatment of HIV-1 infection offers promise for overcoming the problems of toxicity and development of resistance. Primary HIV-1 isolates from three patients before and after treatment with azidothymidine (AZT) were examined for sensitivity to AZT and synergistic response to three different combinations of drugs: AZT+fluorothymidine (FLT), AZT+dideoxyinosine (ddI), and FLT+ddI. All three patients initially harbored AZT sensitive virus, but posttherapy isolates were resistant to AZT. The pretreatment, AZT-sensitive virus from each patient showed synergistic inhibition by the combinations of AZT+FLT, AZT+ddI, and FLT+ddI. In contrast, the posttreatment, AZT-resistant virus showed only addition or antagonism by the combinations containing AZT, whereas the synergistic response to the combination of FLT+ddI was preserved. Our study argues for early intervention with combination chemotherapy, since after development of resistance, AZT no longer showed synergy but addition or antagonism in combination with other drugs. After resistance to AZT has developed, combination chemotherapy not involving AZT may offer advantages over continued mono- or combination therapy involving AZT. PMID- 1520537 TI - Glutathione and N-acetylcysteine suppression of human immunodeficiency virus replication in human monocyte/macrophages in vitro. AB - Glutathione (GSH), its derivatives and N-acetylcysteine (NAC) inhibit the induction of HIV-1 expression in a chronically HIV-1-infected promonocytic cell line (U1/HIV) and peripheral blood mononuclear cells (PBMC). We have examined the effects of GSH and NAC on HIV-1 replication in human primary monocyte/macrophages cultured in vitro. Ficoll-gradient purified human monocytes were cultivated in vitro for 7-10 days and then infected with HIV-1 (Bal and Ada-M). Infection was blocked or substantially reduced by GSH or NAC (5-20 mM). Significant reduction (greater than or equal to 90%) in the amount of virus released, as determined by measuring supernatant reverse transcriptase activity and secreted p24 protein, was obtained when the cells were treated for 4 h with greater than or equal to 10 mM of GSH or NAC. The inhibitory effects of GSH and NAC were concentration dependent. This anti-HIV-1 effect persisted in these cultures for at least 35 days without evidence of significant increase in HIV-1 expression. Thus, a single pulse exposure of HIV-1-infected monocyte/macrophages with GSH or NAC led to a sustained, concentration-dependent decrease in HIV-1 p24 antigen levels, as well as, reverse transcriptase activity without producing detectable cellular toxicity in monocyte/macrophages. PMID- 1520538 TI - Plasma HIV-1 viremia in HIV-1 infected individuals assessed by polymerase chain reaction. AB - We established a method to estimate the amounts of HIV-1 particles in plasma from patients with HIV-1 infection by using polymerase chain reaction (PCR) following reverse transcription (RT) of viral RNA (RNA-PCR) and assessed the potential usefulness of this approach to monitor the changes of viral load in patients with AIDS or AIDS-related complex (ARC) receiving 2',3'-dideoxyinosine (ddI). Plasma samples were obtained from 77 patients with HIV-1 infection (49 AIDS/ARC and 28 asymptomatic seropositives). Following ultracentrifugation of plasma, RNA was extracted from the pelleted virus and subjected to RT and PCR. The number of HIV 1 virus particles in each sample was determined using known amounts of HIV-1 DNA as reference control for PCR. The current plasma RNA-PCR technique quantitatively detected HIV-1 particles in plasma from 76 of 77 (98.7%) HIV-1-infected individuals examined. The numbers of HIV-1 particles in plasma from patients with AIDS or ARC were markedly higher than those in plasma from asymptomatic seropositive individuals (p less than 0.0001). Higher levels of plasma HIV-1 particle numbers were detected in individuals with lower CD4+ T cell counts. Patients (n = 10) who received oral ddI at doses greater than or equal to 6.4 mg/kg/day for 8 to 14 weeks had a profound decrease in plasma HIV-1 particle numbers (p = 0.0051). Patients (n = 7) receiving ddI for 45 to 71 weeks also had a decrease (p = 0.018). It should be noted, however, that more research is required to evaluate the usefulness of this technique in assessing the disease status and monitoring the activity of antiretroviral therapy. PMID- 1520539 TI - Quantitation of human immunodeficiency virus (HIV) with respect to disease stage and zidovudine (AZT) therapy. AB - Quantitation of HIV in 115 seropositive individuals was undertaken to evaluate the potential for HIV transmission as a nosocomial infection through the use of medical devices that may come in contact with the peripheral blood of HIV infected individuals. The virus burden in the peripheral blood was estimated from the level of: plasma HIV p24 antigenemia; plasma viremia; p24 antigen in peripheral blood mononuclear cell (PBMC) lysates as indicators of productive infection; and frequency of latently infected cells. Negligible HIV levels were observed in the plasma and PBMC lysates of the majority of samples except for late-stage patients with certain opportunistic infections and/or lack of zidovudine (AZT) therapy. Some individuals on AZT therapy and at late-stage of disease may show antigenemia without plasma viremia or alternatively, plasma viremia may be observed without plasma antigenemia. PBMC lysate data indicated that the frequency of productively infected cells was less than one in 20,000 PBMCs for the majority of samples irrespective of status on AZT therapy or disease stage. HIV was detected in greater than 95% of the cocultures and within 14 days for most of the samples, again regardless of the stage of disease or status on AZT therapy. The frequency of latently infected cells in this cohort ranged from 125 to 3125 per million PBMCs and was calculated to be as high as 2.5% of the helpter T-cell (CD4+ cell) population in the peripheral blood. The average latently infected cell frequency was 2-3-fold higher in early stage patients not on AZT than in late-stage patients on AZT therapy. PMID- 1520540 TI - Detection of HIV-1 genome in leukocytes of human colostrum from anti-HIV-1 seropositive mothers. AB - In order to obtain more information about the presence of HIV-1 in mononuclear cells of colostrum, research was carried out on both the HIV-1 genome in the cellular fraction of colostrum and the viral antibody in cell-free colostrum of eight anti-HIV-1 seropositive asymptomatic mothers. In five cases cell fractions of the colostrum harbored HIV-1 genome by DNA-DNA and DNA-RNA in situ hybridization, whereas viral antibody were detected in all cell-free colostrum specimens. The data confirms the colostrum as a possible route of HIV-1 infection. PMID- 1520541 TI - Hyperimmunoglobulinemia in HIV-1 infected individuals does not clearly correlate with plasma levels of IL-6. AB - In this study we evaluated interleukin-6 (IL-6) plasma levels in 80 human immunodeficiency virus type 1 (HIV-1) seropositive (+) individuals and 51 HIV-1 seronegative (-) blood donors. Plasma IL-6, detectable only in a subset of HIV 1(+) individuals (45 of 80) and normal blood donors (28 of 51), was significantly (p less than 0.01) increased in HIV-1(+) subjects 187 +/- 20.5 vs. 86.3 +/- 14 pg/ml). Among HIV-1-infected individuals, ARC/AIDS patients showed the highest IL 6 values (243.3 +/- 43.3 pg/ml). HIV-1(+) subjects showed, at all the different stages of the disease, a significant increase in total gammaglobulins, particularly IgG (2071 +/- 101 vs 1265 +/- 34 of HIV-1 seronegative controls). Although among HIV-1-infected individuals, the group with detectable plasma levels of IL-6 shows the highest levels of IgG (2243 +/- 146 vs. 1790 +/- 105, p less than 0.05), no positive correlations were observed between plasma levels of IL-6 and total gamma globulins (r = 0.2) or IgG (0.17). IL-6 production was also examined in the endotoxin-free supernatants of peripheral blood cultured monocytes and CD4+ T lymphocytes, in the presence or absence of specific stimuli. The amount of IL-6 released in monocyte and CD4+ T-lymphocyte culture supernatants was similar in 40 HIV-1(+) individuals and 35 HIV-1(-) controls. Our data show that plasma levels of IL-6 are significantly increased in HIV-1 infected individuals, in particular in ARC/AIDS patients. However, such an increase does not strictly correlate with the degree of hypergammaglobulinemia in the same HIV-1-infected individuals. PMID- 1520542 TI - HIV-1 sequence variation between isolates from mother-infant transmission pairs. AB - To examine the sequence diversity of human immunodeficiency virus type 1 (HIV-1) between known transmission sets, sequences from the V3 and V4-V5 region of the envelope gene from four mother-infant pairs were analyzed. The mean interpatient sequence variation between isolates from linked mother-infant pairs was comparable to the sequence diversity found between isolates from other close contacts. The mean intrapatient variation was significantly less in the infants' isolates then the isolates from both their mothers and other characterized intrapatient sequence sets. In addition, a distinct and characteristic difference in the glycosylation pattern preceding the V3 loop was found between each linked transmission pair. These findings indicate that selection of specific genotypic variants, which may play a role in some direct transmission sets, and the duration of infection are important factors in the degree of diversity seen between the sequence sets. PMID- 1520543 TI - Mapping of immunodominant epitopes of the HIV-1 and HIV-2 integrase proteins by recombinant proteins and synthetic peptides. AB - Different parts of the human immunodeficiency virus type 1 and type 2 (HIV-1 and HIV-2) integrase proteins were expressed as TrpE fusion proteins in Escherichia coli and used to screen human sera. In the immunoblot, all HIV/integrase-positive human sera tested reacted with the carboxy-terminal third of the integrase protein. Furthermore, they crossreacted with the same part of the heterologous protein. Half (50%) of the HIV-1/integrase-positive sera additionally detected antigenic epitopes in the amino-terminal third of the HIV-1 protein. Two of the recombinant proteins were used to generate polyclonal rabbit sera, which react with type-common epitopes of both integrase proteins. To map the B-cell epitopes of the HIV integrase proteins in more detail, overlapping decapeptides representing the entire integrase proteins of HIV-1 and HIV-2 were synthesized and used in a pin-based oligopeptide ELISA to scan human sera. This method can define three potential immunogenic epitopes of the HIV-1 integrase and one potential epitope of the HIV-2 integrase. The immunodominant epitopes of the HIV 1 integrase, one localized in the amino-terminal (IDKAQDEHEKYHSNWRAM), one in the central (QMAVFIHNFKRKGGIGGY), and one in the carboxy-terminal (AVVIQDNSDIKVVPRRK) part of the protein were synthesized as oligopeptides and used to test a larger panel of human sera in ELISA (156 HIV-1+ sera and 104 HIV-1- sera). The amino- and the carboxy-terminal epitopes were of equivalent reactivity, while the central part of the HIV-1 integrase seems to be less immunogenic. Nearly 90% of the HIV-1/integrase-positive human sera could be detected by a combination of these three peptides. PMID- 1520544 TI - [Manometric changes induced by antireflux surgery (Nissen) and its relation to pH measurement and clinical findings. An analysis 6 months after the intervention]. AB - We analyzed the preoperative ambulatory 24 hour ph-metric and manometric characteristics in a group of 20 patients treated surgically for gastroesophageal reflux (PGER) by Nissen fundoplication. At 6 months post-surgery they were reevaluated instrumentally (manometric and 24 hour ph-metry) and clinically. All ph-metric parameters of PGER (total reflux time, clearance, number of episodes, number of episodes greater than 5 minutes duration and duration of longest episode) were significantly improved (p less than 0.01-0.05) post-operatively (as globally as by position supine and upright) and this improvement was associated with resolution of symptoms in 19 (95%) patients. Of the manometric parameters evaluated (lower esophageal sphincter pressure--LESP--and length--LESL, peristaltic, triphasic, biphasic, absent and simultaneous waves and relaxation of LES) surgery only produced improvement in the lower esophageal sphincter pressure (LESP) and length (LESL) (p less than 0.001). We conclude that antireflux surgery (Nissen) by improving the pressure and length of the LES is capable of producing clinical and ph-metric remission in almost all (95%) of patients studied six months after. PMID- 1520545 TI - [The efficacy of Plantago ovata as a regulator of intestinal transit. A double blind study compared to placebo]. AB - The effect of Plantago ovata on patients with chronic constipation (CC) with or without irritable bowel syndrome (IBS) has been assessed by a double blind study comprising 20 patients with CC of which 10 had associated IBS. A clinical questionnaire, weight of feces and intestinal transit time measured with radiopaque markers were done. Patients were then randomly distributed, 10 receiving PO and 10 placebo. Similar tests were done after treatment one month later. All patients receiving PO had good results against only one in the placebo group. Frequency of stools increased from 2.5 +/- 1 vs 8 +/- 2.2 stools per week, p less than 0.001 for paired data). A decrease in consistency of stools was also observed in the treated group. Fecal weight and colonic transit time were not significantly modified in placebo patients, while weight increase was observed in the treated ones (124 +/- 71 vs 194 +/- 65, gr/d p less than 0.001 for paired data) as well as a decrease in transit time (48 +/- 15 vs 34 +/- 18 hours p less than 0.05 for paired data). No adverse effects were observed and particularly no flatulence as often seen in patients on bran. PMID- 1520546 TI - [The action of 5-fluorouracil in DMH-induced carcinogenesis in rats]. AB - An experimental model to observe the action of 5-fluorouracil on rats with DMH induced cancer of colon was designed. Ten Wistar rats were injected weekly with 25 subcutaneous doses (21 mg/kg) of DMH, and another ten, coinciding with the last 10 doses of the former, received intraperitoneally 10 mg/kg of the cytostatic agent. The animals were sacrificed 7 days after the last injection and samples of the colon processed by the "Swiss roll" technique. Differences in the weight of the animals and in the localization, size and macro and microscopic type of the tumours encountered, as well as the localization and grade of the dysplasias are studied. PMID- 1520547 TI - [The value of ADA in peritoneal tuberculosis]. AB - The aim of this study was to confirm that ascitic fluid determination of adenosine deaminase activity (ADA) is useful for the diagnosis of tuberculous peritonitis. 109 patients with ascites have been studied; 4 had tuberculous peritonitis and 105 nontuberculous ascites. The mean value of ascitic fluid AQDA was 0.587 +/- 0.2 uKat/l in tuberculous peritonitis and 0.11 +/- 0.1 uKat/l in nontuberculous ascites (p less than 0.001). An ADA value upper than 0.40 uKat/l has a sensitivity of 100% and a specificity of 99% for diagnosing tuberculous peritonitis. Ascitic fluid determination of ADA is simple, cheap and has a good diagnostic accuracy. In countries with high incidence of tuberculosis, measurement of ADA in ascitic fluid should be used as screening test for tuberculosis. PMID- 1520548 TI - [The effects of verapamil in experimental acute pancreatitis in the rat]. AB - Experimental studies have shown that verapamil inhibits pancreatic exocrine secretion. In order to determine whether verapamil has any effect on acute pancreatitis (AP), we undertook an experimental study in Wistar rats. We used 72 animals divided into two groups. In all animals of both experimental groups, AP was induced by ligation of the biliary duct at its entrance in the duodenum. Animals were given saline (NaCl 0.9%), or 0.30 mgrs/hour verapamil. Subgroups of 9 animals, were treated for 6, 12, 18 and 24 hours; 6 animals group were then sacrificed, for biochemical studies (serum amilase, lipase, and calcium; and trypsin and chemotrypsin in the homogenized pancreas); the other 3 animals were used for morphologic study of the pancreas. Verapamil treatment decreased significantly tissue activity of trypsin (p less than 0.001) and chemotrypsin (p less than 0.0001) and increased serum lipase (p less than 0.05), and calcium. There was no statistical difference in serum amylase. Morphological findings include oedema, acinar necrosis, hemorrhage and vasculitis in non treated animals. Only oedema was observed in animals treated with verapamil. These results suggest a beneficial effect of verapamil on experimental AP induced by ligation of the bile duct in the rat. PMID- 1520549 TI - [Liver function tests based on the use of caffeine]. PMID- 1520550 TI - [Esophageal carcinoma after the endoscopic sclerotherapy of varices]. AB - We report the case of a 52-years-old smoking male, diagnosed of liver cirrhosis, who developed a squamous cell carcinoma of the esophagus 36 months after undergoing endoscopic injection sclerotherapy for bleeding esophageal varices. Nine courses with 3% polidocanol were performed along 10 months. It was injected intra and paravariceal at a total dose of 117 ml. The relationship between endoscopic injection sclerotherapy and developing squamous cell carcinoma of the esophagus is discussed. PMID- 1520551 TI - [Solitary neurofibroma of the esophagus]. AB - A case of solitary neurofibroma located in the mid-portion of the esophagus in a 61-year-old woman is reported. She was operated with the diagnosis of benign tumor of the esophagus (leiomyoma). The microscopic examination of the tumor tissue found nervous cells. The immunohistochemistry analysis confirmed neurofibroma. PMID- 1520552 TI - [Eosinophilic gastritis: its spontaneous resolution]. AB - A 34-year-old man presented with acute epigastric pain. Laboratory studies disclosed a total eosinophil count 7.7 x 10(9)/l. The pathological diagnosis was eosinophilic gastritis. There was a spontaneous resolution, and no treatment was required. Investigations for allergic disorders gave negative results. PMID- 1520553 TI - [Anal polypoid tumor formation as the form of presentation of rectal gastric heterotopia]. AB - Heterotopic gastric epithelium occurs in all portions of the alimentary tract, but it is extremely rare in the rectum. The authors report the finding of a pedunculated anal polyp in a 9-year-old girl with a six-month history of rectal bleeding. Microscopically, the polyp consisted of epithelium of the fundic type. Both the age of the patient and the finding of heterotopic epithelium of the fundic type alone supports a congenital malformation and not an inflammatory condition. PMID- 1520554 TI - [Isolated mesenteric tuberculosis as the first manifestation of AIDS]. AB - We report a case of mesenteric tuberculosis. Two painful abdominal masses and fever were the first manifestation of disease. Diagnosis was obtained by aspirative punction of a mesenteric adenopathy guided by ultrasonography. AIDS risk factors were not recognized by anamnesis but serum HIV antibodies were detected. Thus, extrapulmonary tuberculosis and the finding of HIV-Ab confirmed the diagnosis of AIDS in our patient. It is necessary to assay for HIV-Ab in extrapulmonary tuberculosis, especially when mesenteric tuberculosis is present. PMID- 1520555 TI - [Melanoma metastasis to the pancreas]. PMID- 1520556 TI - [A giant cyst of the mesentery]. PMID- 1520557 TI - [The prevalence of serum markers of the hepatitis B virus in the personnel of a general hospital]. PMID- 1520558 TI - [The hepatic form of Q fever]. PMID- 1520559 TI - [An analysis of a general prospective series of 3270 upper digestive hemorrhages]. AB - The results of a global (general series of 3,270 episodes of upper gastrointestinal haemorrhage (UGH) admitted to our unit between the 15th of April 1983 and the 15th of April 1988 have been analyzed. All the patients entered a prospective protocol with 29 variables. Diagnostic and therapeutic approaches had previously been defined. The incidence of UGH in this area was 160 bleeding episodes/100,000 inhabitants/year. Mean age was 57 +/- 16.8 years and male/female ratio was 2.66/1. The percentage of patients older than 65 years was 33.85%. A history of non-steroidal anti-inflammatory drugs (NSAID) intake within 48 hours before the bleeding episode was obtained in 27.63%. Continued alcohol ingestion was observed in 25.96% and 34.37% of patients gave a history of a previous episode of bleeding. UGH presented with haematemesis and melena in 56% of cases, and 44% only with melena. On admission the bleeding was haemodynamically severe in 12.96% and a 19.69% of the patients had severe associated diseases. Early endoscopy in cases with UGH due to peptic ulcer revealed active bleeding in 16.35% (2.87% in jet and 13.48% oozing) and recent clot/visible vessel in 31.7%. The major causes of bleeding were peptic ulcer (54.31%), esophageal and gastric varices (10.73%) and acute lesions of the gastric mucosa (ALGM) (6.72%). Etiology of the haemorrhage could not be established in 8% of cases. Bleeding was persistent in 20.75% and limited in 79.25% of patients. Emergency surgery was needed in 14.43% of cases. The global mortality of the series was 7.65%.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1520560 TI - [Hypothalamic descending connections]. PMID- 1520561 TI - [Electrophysiology of reflexes]. PMID- 1520562 TI - [The thalamic changes in progressive supranuclear palsy]. AB - This report is to investigate neuropathological changes of the thalamus observed in progressive supranuclear palsy. Six autopsy cases were examined. They were 5 males and a female, whose age was between 57 and 72 years old. They developed dementia in various degrees and three of the cases showed periodic stuporous state and akinetic mutism in the last stage. The paraffined thin-sections were stained with hematoxylin-eosin, luxol-fast-blue, Holzer, modified Bielschowsky, Gallyas and anti-tau stainings. The histological changes were evaluated in the aspects of neuronal loss, fibrillary gliosis and neurofibrillary tangles. In conclusion, there were three types in six cases. The first was seen in two cases and that there appeared many Alzheimer's neurofibrillary tangles (NFTs) in medial nuclei, lateral and ventral nuclei as well as zona incerta and reticular nucleus. The second was observed in two cases and that the loss of nerve cells was severe, especially in medial nuclei and the dorsal part of lateral and ventral nuclei and fibrillary gliosis was observed beyond the lesions of neuronal loss. The third was that the appearance of NFTs was moderate in number and neuronal loss was minimal. Moreover, neuronal loss and NFTs of zona incerta were common in these cases. Argentophilic fibrillary inclusions were observed in the neuropil and astrocytes in all cases. It is important to investigate the correlations between neuropathological changes and clinical manifestations, especially in the peculiar type of dementia observed in PSP. The thalamic changes of PSP may play an important role in causing stuporous state and akinetic mutism as well as subcortical dementia. PMID- 1520563 TI - [Changes in dementia after shunt surgery for normal pressure hydrocephalus]. AB - In order to investigate the pathogenesis of normal pressure hydrocephalus (NPH), dementia was analyzed with regard to the characteristic preoperative picture, the time when dementia improved, and what aspect of dementia was improved, retrospectively. Twenty seven patients of NPH were divided into two groups; young adult group: patients under 64 years old and geriatric group: patients above 65 years old. We found that the only difference found between these two groups was severity in dementia grading, higher in geriatric group. Postoperative course or complications did not differ. Dementia in NPH was not an essential impairment of intellectual ability, but was characterized by the subset symptoms of dementia, such as decrease in spontaneity and interest, slowness and paucity of thought and action. Improvement of memory followed postoperative recovery of these subset symptoms which was observed at earliest three days after shunt surgery. We postulate that recovery of dementia in NPH is associated with not only a decrease in intracranial pressure but also an improvement in the microcirculation of the brain or an improved metabolism. PMID- 1520564 TI - [Correlation between the analgesic effect by thalamic relay nucleus stimulation and somatosensory evoked potentials recorded from thalamus]. AB - Electric stimulation of the thalamic sensory relay nucleus (Vc) has an analgesic effect on deafferentation pain, however, the analgesic effect differs from patient to patient. Electrode position and state of the substrate stimulated are considered important factors influencing the analgesic effect. In order to determine the best position for the stimulating electrodes, we recorded somatosensory evoked potentials (SEPs) from stimulating electrodes implanted in the Vc and compared thalamic SEPs with the analgesic effect of Vc stimulation. The subjects were thirteen patients with deafferentation pain, four patients with thalamic lesions, seven patients with suprathalamic lesions and two patients with infrathalamic lesions. We inserted the electrode array into the Vc stereotactically, and fixed it so that stimulation-induced paresthesia would cover the painful frea. The electrode array consisted of the four contact points of four electrodes spaced at 2 mm intervals within 10 mm from the tip. Using bipolar combinations of the four electrodes (twelve combinations in all), we stimulated the Vc for about half an hour with each combination. We then rated the degree (%) of analgesia as 100% when pain disappeared and 0% when there was no change. Thalamic SEPs elicited after stimulation of the contralateral median nerve were recorded from all four contact points simultaneously. The latencies, amplitudes and recorded positions of large early positive components (P1) followed by large negative components (N1) with latencies between 10 and 20 msec were then analyzed and compared with the best electrode combination for optimal pain relief and with the degree of analgesia.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1520565 TI - [Neuritic degeneration in Alzheimer-type dementia, with special reference to the presence of dark neurites]. AB - Four cases of neuritic degeneration in the cerebral cortex of Alzheimer-type dementia patients have been examined by routine and Gallyas-silver electron microscopy. This examination has revealed neuritic changes described below. (1) Dendrites and axons with an increased electron density (dark neurites) were found scattered throughout the neuropils, these dark neurites thought to be either degraded neurites resulting from simple neuronal atrophy or retrograde and/or transsynaptic degeneration due to an axonal injury within the senile plaques. (2) Both dystrophic neurites and neuropil threads were found scattered throughout the neuropils and showed some similarities in producing abnormal substances in their processes and in their manner of aggregating, especially within the senile plaque region. These degenerated neurites may have been caused by neurotoxicity of the amyloid. On Gallyas electron microscopic inspection, neurites often are found to have small fibrous and sometimes tubular structures on which silver particles are deposited. This finding may represent the initial stage of a neurofibrillary change. (3) The regeneration of neurites though such ultrastructures is not known, but such concept is believed by many authors and is discussed. PMID- 1520566 TI - [A patient with gigantic heterotopic gray matter with epileptic seizures]. AB - We report a patient with partial seizure and gigantic heterotopic gray matter. A 23-year-old young man was admitted to our hospital with complaints of frequent epileptic seizures and psychiatric symptoms. There was psychomotor delay in infancy. At the age of 4 years, afebrile convulsions appeared on several occasions. Seizures characterized by a lapse of consciousness started at the age of 13 years. He often stayed in a fantasy world and became very emotional at such time. Cranial CT demonstrated an irregularity in the wall of right lateral ventricle and disappearance of the posterior horn on the same side. This lesion, adjacent to that wall, had a signal intensity that was similar to that of the gray matter on each sequence in MRI. Histopathology of this lesion showed a number of large and small neurons. Therefore, heterotopic gray matter was diagnosed. MRI demonstrated wide cortices suggesting polymicrogyria in the right parietal lobe. Complex partial seizures with eye deviation to the left were recognized. Interictal EEG showed frequent high voltage spikes in the right temporal, fronto-temporal and parieto-occipital areas independently. Therefore, epileptic foci were thought to exist in or around those lesions. PMID- 1520567 TI - [Unilateral choreic movements in idiopathic hypoparathyroidism]. AB - We report a patient with idiopathic hypoparathyroidism associated with unilateral calcification of the basal ganglia and contralateral choreic movements. A 66-year old woman was admitted to our hospital because of involuntary movements of the left limbs. Two years before the present admission, she had operations for bilateral cataracts. Eight months before admission, she had an onset of severe carpal spasms and pain in both arms and legs. These symptoms improved after one month's rest in a hospital. About a month before admission, she noted progressive difficulty in using her left hand, followed by difficulty in walking due to the abnormal involuntary movement of the left lower limb. Two weeks before admission her carpal spasms appeared again, bilaterally. On admission, she was alert. The general physical examination was normal. Neurological examination revealed choreic movements in the left hand, arm, leg and neck, and grimacing of the left face. She also complained of the spasms and pain in her hands, dysarthria and shortness of the breath. Chvostek and Trousseau signs were positive. Laboratory examination revealed marked decrease in serum calcium level (2.57 mEq/ml) and increase in inorganic phosphorus level (6.40 mEq/ml). Serum level of parathyroid hormone was less than 10 pg/ml. Ellthworth-Howard test was positive, in that the infusion of parathyroid hormone (100 u) elicited a marked increment of the urinary excretions of phosphorus and cAMP. X-ray examination of the spine revealed ossification of the posterior longitudinal ligament in the cervical region. CT-scans of the brain revealed calcification in the region of right globus pallidus and putamen.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1520568 TI - Masahiro Iio Memorial Lecture. PMID- 1520569 TI - Physiologic capacity of well-developed collaterals in patients with isolated left anterior descending artery disease. AB - To assess the physiologic significance of well-developed collaterals, 34 patients, with isolated left anterior descending artery disease (LAD) and without overt prior myocardial infarction, underwent cardiac catheterization and exercise thallium-201 emission computed tomography. The patients were divided into 3 groups; 11 patients with 90% stenosis of the proximal LAD and without collaterals (group 1), 11 with 99% stenosis of the proximal LAD, and without collaterals (group 2) and 12 with a total occlusion of the proximal LAD which was completely filled by well-developed collaterals (group 3). On left ventriculography, shortening fractions of the anterior wall were significantly reduced in group 2 as compared to group 1 and 3 (group 1 vs group 2: p less than 0.01, group 2 vs group 3: p less than 0.05), which reflected the lower ejection fraction of group 2 (p less than 0.01 and p less than 0.05, respectively). The perfusion defects of the anterior wall on both the initial and the delayed images were severer in groups 2 and 3 than in group 1 (group 1 vs group 2 and group 1 vs group 3 on the initial image: p less than 0.01, for both, group 1 vs group 2 and group 1 vs group 3 on the delayed image: p less than 0.05, for both). However, recovery of the perfusion defects from the initial image to the delayed image was better in group 3 than in groups 1 and 2 (group 1 vs group 2 and group 1 vs group 3: p less than 0.05, for both). Therefore, coronary blood flow through well-developed collaterals was considered to be comparable to the flow through a diseased vessel with 90% stenosis at rest. During maximal exercise, blood flow through well developed collaterals was considered to be comparable to the flow through a diseased vessel with 99% stenosis, although the blood flow through well-developed collaterals was considered to be better than that through 99% stenosis during the recovery period. These findings suggest that patients with well-developed collaterals must be treated like those with severe stenosis. PMID- 1520570 TI - Pharmacokinetic analysis of antibody localization in human colon cancer: comparison with immunoscintigraphy. AB - The biodistribution and imaging characteristics of the 111In-labeled anti CEA monoclonal antibody ZCE-025 were studied in five patients with suspicion of colorectal carcinoma. Evaluation included antibody pharmacokinetics and assessment of antibody distribution in surgical specimen, making a comparison with whole-body imaging with a gamma camera. ZCE-025 localization in tumors was demonstrated by gamma-camera imaging in 4 of the 5 patients, corresponding to surgical findings. Persistent accumulation of 111In in the lymph nodes was observed in one patient, whereas surgical exploration of these lymph nodes showed no gross or microscopic evidence of metastases of colon carcinoma. Analysis of individual plasma by size exclusion HPLC showed two radioactivity peaks, labeled antibody and free DTPA. No transchelation of 111In to circulating transferrin was observed. The blood clearance was fitted to a two-compartment equation and its half-lives were found to be 10.8 +/- 8.7 h and 69.5 +/- 21.8 h for t1/2 alpha and t1/2 beta, respectively. Total urinary excretion averaged 0.3% of the injected dose/h with a small patient to patient variation. At 24 hrs postadministration the predominant radiolabeled species in urine was free DTPA. Thereafter, radioactivity in urine was partly present as a low molecular weight catabolic product. No apparent correlation between CEA content and uptake of 111In-ZCE-025 in tumors resected by surgery could be found. How 111In-labeled antibody is accumulated into tumors as well as into some nontumor tissues needs further study. PMID- 1520571 TI - The causes and clinical significance of exercise-induced silent myocardial ischemia evaluated by ischemic range and intensity with exercise Tl-201 myocardial SPECT. AB - We investigated the causes and long-term prognosis of exercise-induced silent myocardial ischemia (SMI) by means of exercise Tl-201 myocardial SPECT (Ex-SPECT) in 97 patients with effort angina or old myocardial infarction (OMI). These patients were proven to have significant stenosis by coronary angiography. The subjects were divided into three groups based on the presence or absence of Tl 201 redistribution or angina during exercise testing. Group one consisted of 34 patients who had redistribution on Ex-SPECT and angina during exercise testing: the painful myocardial ischemia (PMI) group. The second group consisted of 38 patients who had redistribution on Ex-SPECT, but no angina during exercise testing: the SMI group. The third group consisted of 25 patients who had no redistribution: the RD (-) group. The ischemic range and intensity were quantified by the defect volume ratio (DVR) and defect severity index (DSI), respectively. Comparison of the DVR and DSI values for the PMI and SMI groups revealed that the DVR and DSI values for the SMI group were lower than those of the PMI group. Also the prognosis of the SMI group tended to be worse than that of the RD (-) group. Thus, we concluded that the SMI and PMI group should receive identical treatment. PMID- 1520572 TI - Myocardial uptake of antimyosin antibody compared with serum myosin light chain I levels in patients with myocardial infarction. AB - Myocardial accumulation of In-111-antimyosin (InAM) was evaluated in comparison with circulating serum myosin light chain I (LCI) level at the time of InAM injection. Seventeen consecutive patients were studied at various stages ranging from 6 days to 34 days after myocardial infarction (MI). The infarct area was positive for InAM uptake in all patients (100%), and significant myocardial uptake was observed in 14 patients (82.4%). The intensity of InAM uptake correlated with the infarct location shown by ECG and CAG. In contrast, 12 patients (70.6%) had normal or undetectable serum myosin LCI levels, with 5 being normal (0.42-2.5 ng/ml) and 7 undetectable (0.42 ng/ml or less). Only 5 patients (29.4%) had elevated serum myosin LCI levels at the time of InAM injection, and this elevation was slight, ranging from 3.4 to 4.5 ng/ml (mean: 3.75 ng/ml). Among patients with undetectable, normal, and elevated serum myosin LCI levels, there was no significant correlation between InAM uptake and the serum myosin LCI level. Thus, even after the serum myosin LCI level has decreased to normal, InAM can still bind to cardiac myosin in patients with MI, presumably until there is complete recovery from the hibernating myocardium due to ischemic damage. PMID- 1520573 TI - Preoperative evaluation of myocardial viability by thallium-201 imaging in patients with old myocardial infarction who underwent coronary revascularization. AB - The myocardial uptake and redistribution in thallium scintigraphy and the regional wall motion by echocardiography were evaluated by a semi-quantitative method in 42 patients who previously had myocardial infarction (50 target vessels) and underwent coronary revascularization. The aim of this study was to elucidate the significance of the initial image, delayed image and redistribution on thallium-201 scintigraphy for clinical diagnosis of the myocardial viability. As a semi-quantitative analysis, we used a bull's-eye display for thallium image and centerline method for echocardiographic wall motion, and compared the results before and after revascularization. As a result, the thallium grade improved postoperatively in all 17 areas which preoperative had showed redistribution, and also in 11 of the 32 areas without preoperative redistribution. The sensitivity, specificity and accuracy of preoperative thallium redistribution for predicting myocardial viability were 61%, 100% and 78%, respectively, when the postoperative improvement in the thallium grade was used as the standard. The postoperative probability of improvement in the thallium grade increased in proportion to the preoperative thallium grade (delayed image) (p less than 0.01). There was no correlation between the preoperative thallium delayed image and postoperative improvement in wall motion. Postoperative improvement in thallium image and wall motion could not be predicted from the preoperative wall motion. Thus, postoperative improvement in thallium images can be anticipated if redistribution is present on the preoperative thallium image, and the preoperative thallium delayed image is useful for predicting myocardial viability. Improvement in wall motion could not be predicted preoperatively by these methods. PMID- 1520574 TI - Application of 67Ga for the estimation of reticulocyte production. AB - In order to estimate the production of reticulocytes, which have a larger number of transferrin receptors than erythrocytes, we used 67Ga which is exclusively bound to transferrin in the blood. The pattern of uptake of 67Ga by reticulocytes was quite similar to the time course of transglutaminase activity which might be involved in receptor-mediated endocytosis. The preinjection of Fe3+ decreased the uptake of 67Ga by reticulocytes. These results suggested that 67Ga in a transferrin-bound form was taken up by reticulocytes via receptor-mediated endocytosis. It was showed that the application of 67Ga is very easy and useful for the estimation of reticulocyte production. PMID- 1520575 TI - Tc-99m-HMDP bone uptake quantification and plasma osteocalcin levels in hemodialysis patients--a preliminary study. AB - In this preliminary study plasma osteocalcin levels and Tc-99m-HMDP (Technetium 99m hydroxymetylene diphosphonate) bone uptake (BU) were measured in 10 chronic end-stage renal failure patients who were on maintenance hemodialysis. The aim of this study was to determine the correlation between bone uptake and osteocalcin-a sensitive and specific marker of osteoblastic activity. There was a statistically significant increase in both 20 and 180 minute uptake in the patient group (36 +/ 2.7 and 39 +/- 3.6) when compared to the normal volunteers (32 +/- 3.1 and 19 +/ 2.7). Plasma osteocalcin levels were also significantly high (24.5 +/- 5.6 ng/ml) when compared with normal values (6.5 +/- 2.3 ng/ml). The correlations between osteocalcin and 20 and 180 min BU were high (r = 0.62 and 0.72 respectively). In conclusion, our preliminary study suggests that, in hemodialysis patients, Tc-99m-HMDP bone uptake quantification is a sensitive and non-invasive method for showing increased osteoblastic activity. PMID- 1520576 TI - Environmental pollution. Biological monitoring of human exposure to environmental lead. PMID- 1520577 TI - Expanded programme on immunization. Sentinel school surveillance programme for immunization status and vaccine-preventable diseases. PMID- 1520578 TI - American Association for Cancer Education, 26th annual meeting. Buffalo, New York, October 1-4, 1992. Abstracts. PMID- 1520579 TI - Germline mutations in the p53 tumour suppressor gene: scientific, clinical and ethical challenges. PMID- 1520580 TI - Recognition and killing of tumour cells expressing heat shock protein 65 kD with immunotoxins containing saporin. AB - The expression of heat shock proteins (HSP) of the 65 kD family (groEL) has been observed by flow cytometry using murine monoclonal antibody (MoAb) anti-HSP 65 kD (ML30) on the surface of B (Daudi) or T (H9) lymphoma cells, on a monocyte cell line (U937) and also on a primary culture of a human pancreatic carcinoma (HPC). Moreover, the MoAb ML30 was coupled to Saporin 6, a ribosome-inactivating protein recovered from the seeds of Saponaria officinalis, to kill HSP-expressing cells with a specific immunotoxin. An indirect method using first MoAb ML30 and then anti-mouse IgG1 immunotoxin was also performed. With this method a human serum positive for HSP65-antibodies was tested using anti-human IgG1 or IgM immunotoxins. All cell lines were inhibited when preincubated with the specific immunotoxin directed to HSP65 (ML30 SO6), although H9 cells were susceptible to immunotoxin only after thermal stress. Daudi and HPC cells were inhibited both after long-term culture and when freshly explanted from SCID mice. Proliferation of the U937 monocytic cell line, that constitutively expresses high levels of HSP65 on the surface (as determined by flow cytometry), was completely inhibited (100% inhibition) by the ML30 SO6. However, not all tumour cells constitutively express high levels of surface HSP65, as determined by cytometric analysis. For this reason it was not always possible to obtain complete inhibition of cellular proliferation. PMID- 1520581 TI - Chlorambucil-monoglutathionyl conjugate is sequestered by human alpha class glutathione S-transferases. AB - The spontaneous reaction of 110 microM chlorambucil (4-[p-[bis(2 chloroethyl)amino]phenyl]-butanoic acid; CHB) with 5 mM GSH at 37 degrees C in physiological phosphate-buffered saline for 35 min gave primarily the monoglutathionyl derivative, 4-[p-[N-2-chloroethyl,N-2-S glutathionylethyl]amino]phenyl]-butano ic acid; CHBSG) and the diglutathionyl derivative, 4-[p-[bis(2-S-glutathionylethyl]amino]phenyl]-butanoic acid (CHBSG2) with small amounts of the hydroxy-derivatives: 4-[p-[N-2-chloroethyl,N-2-hydroxy ethyl]amino] phenyl-butanoic acid (CHBOH) and 4-[p-[N-2-S-glutathionylethyl-2 hydroxyethyl]amino]phenyl]-butanoi c acid (CHBSGOH). The inclusion of approximately physiological amounts of human glutathione S-transferases (GSTs) A1 1, A2-2, P1-1, M1a-1a M3-3 or P1-1 (for nomenclature see Mannervik et al., 1992, Biochem. J., 282, 305) had little or no catalytic effect on these reactions as determined by loss of CHB. However, GTSs A1-1 and A2-2 were associated with a significant increase of CHBSG at the expense of CHBSG2 + CHBSGOH suggesting that these GTs sequestered CHBSG at the active site. This interpretation was supported by inhibition studies which showed that CHBSG was a pure competitive inhibitor of the activity of GSTs A1-1 and A2-2 towards 1-chloro-2,4-dinitrobenzene with Ki's of 1.3 and 1.2 microM respectively. GSH transferases P1-1 and M1a-1a were inhibited by CHBSG above 10 microM. Incubation of 2 microM CHB, a concentration which may be of more significance for chemotherapy, in the presence or absence of GST A1-2 (20-50 microM) showed catalysis of GSH monoconjugation equivalent to 18% of the spontaneous rate. However, the dominant effect again was the sequestration of CHBSG which reached 74.3 +/- 1.5 (SEM)% of the total reactants at 60 min compared to 28.9 +/- 0.3(SEM)% in controls. CHBSG, although possessing a potential electrophilic centre, showed no detectable alkylation of plasmid DNA but indirect evidence was obtained that it alkylated other cellular macromolecules. It is concluded that the contribution of GSTs to catalysis of CHB detoxication will depend on factors not previously considered, namely the relative molarities of CHB, CHBSG and GSTs, and the cellular capacity to excrete CHBSG to relieve product inhibition. PMID- 1520582 TI - Photodynamic therapy of the normal rat stomach: a comparative study between di sulphonated aluminium phthalocyanine and 5-aminolaevulinic acid. AB - Dysplasia in the upper gastrointestinal tract carries a risk of invasive malignant change. Surgical excision of the affected organ is the only treatment available. Photodynamic therapy has been shown to be promising in the treatment of early and superficial tumours and may be useful for the ablation of dysplastic mucosa. Because of the diffuse nature of the disease, such treatment would necessarily involve destruction of large areas of mucosa and it is desirable to confine its effect to the mucosa in order that safe healing can take place. By means of photometric fluorescence microscopy, we have studied the pattern of photosensitisation in the normal rat stomach using di-sulphonated aluminium phthalocyanine (AlS2Pc) and 5-aminolaevulinic acid (ALA) as photosensitisizers. AlS2Pc resulted in a panmural photosensitisation of the gastric wall with the highest level encountered in the submucosa. The mucosa and muscularis propria were sensitised to equal extent. Following light exposure, a full thickness damage resulted. ALA is a natural porphyrin precursor and exogenous administration gave rise to accumulation of protoporphyrin IX (PPIX) in the cells. The resultant pattern of photosensitisation was predominantly mucosal and its photodynamic effect was essentially confined to the mucosa. ALA produced a selective photosensitisation of the gastric mucosa for its photodynamic ablation with sparing the underlying tissue layers. PMID- 1520583 TI - Interactions between human monocytes and tumour cells. Monocytes can either enhance or inhibit the growth and survival of K562 cells. AB - Human bloodstream monocytes can kill cultured tumour cells (K562), as assessed by specific release of 51Cr from the targets and by inhibition of 3H-thymidine incorporation. Confluent monolayers of monocytes were required for maximal cytotoxicity, and the density of the K562 cells was also an important factor. For example, when K562 cells were seeded at high cell densities, they were killed during incubation with monocytes, but when seeded at low cell densities their growth and survival was enhanced during culture with monocytes. The factor(s) which promoted the survival and division of low density K562 cultures was endogenously secreted from monocytes as it was present in monocyte-conditioned medium, whereas the cytotoxic factor(s) were only expressed during co-culture of monocytes with K562 cells. Conditioned medium from HL 60, U-937, HeLa and K562 could also enhance the growth and survival of low density K562 cultures, and a similar effect was also observed upon the addition of catalase and superoxide dismutase to such cultures. Thus, the monocyte:target ratio is important in determining whether monocytes exhibit cytotoxic or growth-promoting effects and hence tumour-derived or monocyte-derived reactive oxidant species may play a role in tumour cell cycle regulation. PMID- 1520584 TI - The induction of bladder cancer in portally diverted rats. PMID- 1520585 TI - A monoclonal antibody-beta-glucuronidase conjugate as activator of the prodrug epirubicin-glucuronide for specific treatment of cancer. AB - The anti-pan carcinoma monoclonal antibody (MAb) 323/A3, linked to E. coli derived beta-glucuronidase (GUS) was used to study the tumour-site-selective activation of the prodrug Epirubicin-glucuronide (Epi-glu). Epi-glu was isolated from the urine of patients treated with Epirubicin (Epi) by reversed phase chromatography on a silica-C18 column. Epi-glu was stable in human blood and was not converted into Epi by A2780, MCF-7, or OVCAR-3 cancer cells, despite the presence of intracellular GUS. The stability of the prodrug was confirmed in BALB/c mice. MAb 323/A3 and GUS were linked through a stable thioether bond. The conjugate (1:1) was purified by ion exchange and gel filtration chromatography. Binding to target cells revealed an immunoreactivity of at least 60% and good retention of enzyme activity. A protein dye (sulforhodamine B) assay was used to analyse cytotoxicity. Epi (IC50 of 0.003-0.2 microM) was 100-1,000 times more toxic than Epi-glu (IC50 of greater than 20 microM), when cancer cells were exposed for 4 or 24 h to the drugs. The low cytotoxicity of Epi-glu was most likely due to the reduced cellular uptake rate of the prodrug (2.7 pmol 10(-6) cells min-1) as compared to that of the parent compound (25 pmol 10(-6) cells min 1). Pretreatment of antigen-positive cells with the 323/A3-GUS conjugate prior to prodrug exposure completely restored cytotoxicity as a result from hydrolysis of Epi-glu into Epi. Our results demonstrate that the 323/A3-GUS conjugate can specifically activate the stable non-toxic prodrug Epi-glu at the tumour cell level. PMID- 1520586 TI - Radioimmunotherapy of human head and neck squamous cell carcinoma xenografts with 131I-labelled monoclonal antibody E48 IgG. AB - Monoclonal antibody (MAb) E48 reacts with a 22 kD antigen exclusively expressed in squamous and transitional epithelia and their neoplastic counterparts. Radiolabelled with 99mTc, MAb E48 is capable of targeting metastatic and recurrent disease in patients with head and neck cancer. In this study, the capacity of 131I-labelled MAb E48 to eradicate xenografts of human squamous cell carcinoma of the head and neck (HNSCC) in nude mice was examined. Experimental groups received a single i.v. bolus injection of 400 microCi MAb E48 IgG (number of mice (n = 6, number of tumours (t) = 9) or 800 microCi MAb E48 IgG (n) = 5,t = 7), whereas control groups received either diluent (n = 3,t = 5), unlabelled MAb E48 IgG (n = 4,t = 5) or 800 microCi 131I-labelled isotype-matched control MAb (n = 6,t = 9). A 4.1-fold increase in the median tumour volume doubling time and regression of two out of ten tumours (20%) was observed in mice treated with 400 microCi. In mice treated with 800 microCi. In mice treated with 800 microCi, two out of seven tumours (29%) showed complete remission without regrowth during follow-up (greater than 3 months). Median tumour volume doubling time in the remaining five tumours was increased 7.8-fold. No antitumour effects were observed in mice injected with diluent, unlabelled MAb E48 or 131I-labelled control MAb. In the same xenograft model, chemotherapy with doxorubicin, 5 fluorouracil, cisplatin, bleomycin, methotrexate or 2',2'-difluorodeoxycytidine yielded a less profound effect on tumour volume doubling time. Increases in tumour volume doubling time with these chemotherapeutic agents were 4, 2.2, 2.1, 1.7, 0, and 2.6 respectively. Moreover, no cures were observed with any of these chemotherapeutic agents. From the tissue distribution of 800 microCi MAb E48, the absorbed cumulative radiation doses of tumour and various organs were calculated using the trapezoid integration method for the area under the curve. To tumour xenografts, 12,170 cGy was delivered, blood received 2,984 cGy, whereas in every other tissue the accumulated dose was less than 6% of the dose delivered to tumour. These data, describing the first radiolabelled MAb with therapeutic efficacy against HNSCC, suggest radioimmunotherapy with MAb E48 to be a potential therapeutic modality for the treatment of head and neck cancer. PMID- 1520587 TI - Classical oestrogen receptor is not detectable in pancreatic adenocarcinoma. AB - Recent reports have suggested the presence of oestrogen receptors (ER) in pancreatic carcinoma. Therefore the tumour may be sensitive to hormone manipulation therapy. We examined 23 biopsies of human pancreatic carcinoma tissue for the presence of ER. The tissue was assayed by two methods: Iso electric focusing (IEF) and ER-ICA an immunocytochemical assay. All biopsies were tested with ER-ICA and ten by IEF. Each biopsy was assessed histologically for tumour content and 20 contained adenocarcinoma. None of the samples of pancreatic carcinoma were positive for ER using the ER-ICA, and none demonstrated the binding peak typical of ER in the IEF assay. These results suggest that in pancreatic carcinoma oestrogen receptor is either absent (or at very low levels), or of a different type to that found in breast and uterine tissue. On theoretical grounds at least, this must raise questions as to the oestrogen sensitivity of pancreatic cancer. PMID- 1520588 TI - Interstitial laser hyperthermia: a new approach for treating liver metastases. AB - The palliative management of hepatic metastases remains unsatisfactory. There is a need for a simple non invasive technique which can stop or retard the rate of tumour growth. In principle, Interstitial Laser hyperthermia may fulfil such a role. In experimental studies, this technique produced precise in situ necrosis within solid organs which healed safely. In a pilot feasibility study, we treated ten patients with a total of 18 hepatic metastases on 31 occasions using a percutaneous approach to achieve an overall objective response rate of 44%. The treatment proved simple to perform, was well tolerated and produced radiological evidence of necrosis in small metastases (diameter less than or equal to 3 cm). However, further research is required before the technique can be regarded as established. Its future role in most cases will be to control the growth of discrete hepatic metastases unsuitable for resection. In instances where the extent of necrosis can be matched accurately to tumour volume, the potential for cure exists. PMID- 1520589 TI - Prognostic significance of breast cancer axillary lymph node micrometastases assessed by two special techniques: reevaluation with longer follow-up. AB - Special techniques such as serial macroscopic sectioning (SMS) or immunohistochemical staining (IH) improve the detection rate of micrometastases but this detection is of value only if it improves the prediction of recurrence and survival. We first studied the prognosis of 120 patients with a single micrometastasis detected by SMS in a series of 1,680 primary operable breast carcinoma with a median follow-up of 7 years. A significant difference in recurrence (P = 0.005) and in survival (P = 0.0369) was found between node negative patients and those with one single SMS micrometastasis, but SMS micrometastases were not a predicting factor by multivariate analyses according to the Cox model. We then studied the prognostic significance of patients with a micrometastasis detected by IH in node-negative carcinoma: 37 micrometastases from a series of 89 invasive lobular carcinoma (ILC) and 13 single micrometastases from a series of 129 invasive ductal carcinoma (IDC). In the ILC group, IH micrometastases had no prognostic value (median follow-up: 9.3 years). In the IDC group, IH micrometastases were correlated with recurrences (P = 0.01) and were the most significant predicting factor, but were less correlated with survival (median follow-up: 15.6 years). Three main points emerge from this study: (1) SMS micrometastases have a prognostic significance and macroscopic sectioning is recommended as a routine technique not requiring excessive work. (2) IH micrometastases in infiltrating lobular carcinoma have no prognostic significance. (3) The value of IH is debatable in infiltrating ductal carcinoma, since the technique is of principal use in predicting recurrences. It should therefore be carefully assessed vs other prognostic factors currently under study. PMID- 1520590 TI - Tumour growth rate and DNA flow cytometry parameters as prognostic factors in metastatic melanoma. AB - The prognostic value of flow cytometric parameters and tumour growth rate of melanoma metastases under the mouse renal capsule was investigated for tumours from 117 consecutive patients referred to the Helsinki University Central Hospital Melanoma Team. DNA flow cytometry (FCM) was interpretable for the tumours of 114 patients, and growth rate analysis for 82 patients, both results being available from 79 patients. Thirty-six percent of the tumours were DNA diploid and 64% DNA aneuploid. Tumour ploidy and S-phase fraction were shown by multivariate Cox model analysis to be independent prognostic variables and major determinants of survival after first recurrence. Patients with DNA diploid or aneuploid tumours survived a median 16 and 27 months, respectively. A high growth rate of tumour sample in vivo under the mouse renal capsule tended to be a sign of poor prognosis, although not reaching statistical significance. Combining the results of FCM, tumour growth rate and TNM stage, we propose a highly efficient prognostic scoring method. Patients with a score above 0.75 had a median survival of 11 months compared to 30 months among patients scoring under 0.75 (P less than 0.0001). This score was the most significant (P less than 0.0001) prognostic factor in the Cox model when TNM stage, age, ploidy, SPF, and tumour growth rate were analysed as covariates. PMID- 1520591 TI - CMV chemotherapy for advanced transitional cell carcinoma. AB - Between May 1986 and September 1990 a total of 43 patients with metastatic transitional cell carcinoma (TCC) of the urinary tract have been treated at our institution with combination chemotherapy (CMV) consisting of cisplatin 100 mg m 2 i.v. day 2; methotrexate 30 mg m-2 i.v. days 1.8; and vinblastine 4 mg m-2 i.v. days 1.8. Chemotherapy was recycled on day 22 and continued for a maximum of six cycles in responding patients. Of 33 patients with measurable disease 8 (24%) achieved a complete remission (CR). The median survival for patients achieving a CR was 13 months (range 5-29+) whilst the median survival for all 43 patients was 7 months (range 1-29+). Only three patients are still alive--two are disease free. More effective and/or less toxic chemotherapy regimens are needed for the treatment of patients with metastatic TCC. PMID- 1520592 TI - An audit of the quality of cancer registration data. AB - The accuracy of cancer registration data in the East of Scotland (Tayside) Cancer Registry was audited by comparing 200 consecutive registrations (about 10% of the annual total) with the 'gold standard' of the Histopathology records. ICD codes were independently generated by a pathologist by examining final pathology reports and then compared to those codes given by the local cancer registrar. Discrepancies were graded by the pathologist and the epidemiologist according to severity. Major errors of coding were few. Minor and moderate differences in coding occurred because of the nature and structure of the coding system and the manner in which data are retrieved. The level of detail required by the Cancer Registry needs to be evaluated. PMID- 1520593 TI - Expression of beta-2-microglobulin by nasopharyngeal carcinoma. AB - Serum beta-2-microglobulin (beta 2M) levels of 274 Chinese patients with different stages of nasopharyngeal carcinoma at presentation and that of 35 patients who developed distant metastases post-treatment were assayed. beta 2M level was found to increase with advancing stage of disease, with statistically significant differences among early-stage, advanced-stage, and metastatic disease. Elevated pre-treatment beta 2M levels were expressed more frequently by tumours with lower degree of histological differentiation. The sensitivity of serum beta 2M for diagnosis of nasopharyngeal carcinoma, however, is low. PMID- 1520594 TI - Prognostic significance of p53 overexpression in gastric and colorectal carcinoma. AB - p53 expression was examined in 55 gastric and 107 colorectal carcinomas with an immunoperoxidase technique, using the polyclonal antibody CM1 on routinely fixed, paraffin embedded tissue. p53 protein was detected in 47% gastric and in 46% colorectal carcinomas and found to correlate with stage of disease and unfavourable clinical outcome (P less than 0.001). Thus, the proportion of positively reacting neoplasms increased as the stage progressed, tumours which had invaded regional lymph-nodes overexpressed p53 more frequently than localised carcinomas and an elevated level of p53 was associated with early relapse and death. In colorectal carcinoma p53 positivity was also linked with site and macroscopic configuration of the primary tumour and was most frequently expressed in carcinomas from the rectum and in ulcerative tumours. p53 overexpression was irrespective of tumour grade. Uniform negative reactivity with anti-p53 antibody was seen in normal epithelium adjacent to carcinoma, intestinal metaplasia, atrophic gastritis and in colonic adenomas. There was a good correlation between immunohistochemical staining on paraffin and frozen sections. These studies suggest that in gastric and colorectal carcinoma, immunohistochemical detection of p53 protein in routinely fixed tissue can be used along with other established parameters to assess prognostic outcome, especially to identify patients with poor short-term prognosis. PMID- 1520595 TI - Trends in mortality rates from malignant melanoma in Sweden 1953-1987 and forecasts up to 2007. AB - To monitor mortality rates from malignant melanoma we analysed all patients in Sweden (6,324) who died of malignant melanoma in 1953 through 1987. Age standardised rates per 10(5) increased from 1.1 to 4.0 in men and from 1.0 to 2.6 in women. The average annual increase levelled off in men from 4.6% during 1953 1967 to 2.0% in 1978-1987; and in women from 3.7% to 0%. Multivariate analyses showed that the change in rates for men was mainly due to a birth-cohort effect, whereas in women the rates changed similarly in all age-groups in accordance with a time-period effect. The risk of dying of malignant melanoma increased in men for birth cohorts up to 1932, whereas in women the rise continued for cohorts born as late as 1947. The best-fitted multivariate models were extrapolated to the year 2007, among men a slight increase in mortality rates seemed likely, whereas among women the rates will probably remain unchanged. PMID- 1520596 TI - Occupation and bladder cancer: a death-certificate study. AB - Occupational statements on death certificates of 2,457 males aged 25-64 who died from bladder cancer in selected coastal and estaurine regions of England and Wales during 1965-1980 were studied. Excess mortality was found for deck and engine room crew of ships, railway workers, electrical and electronic workers, shoemakers and repairers, and tobacco workers. An excess of cases also occurred among food workers, particularly those employed in the bread and flour confectionary industry or involved in the extraction of animal and vegetable oils and fats. Use of a job-exposure matrix revealed elevated risk for occupations in which most workers were exposed to paints and pigments, benzene and cutting oils. PMID- 1520597 TI - Tumour concentrations of flavone acetic acid (FAA) in human melanoma: comparison with mouse data. AB - Flavone acetic acid (FAA) showed impressive effects against murine solid tumours but no activity in clinical studies. The mechanism of action in mice may involve damage to tumour vasculature or immunomodulation, and these effects may be species-specific. Alternatively, concentrations of FAA achieved in mouse tumours may be higher than in human tumours. It is important to resolve this issue since it raises important questions about the relevance of in vitro versus in vivo tumour screens and the development of FAA analogues. As part of a Cancer Research Campaign Phase II study of metastatic melanoma in which 8.4 g m-2 FAA was given as a 6 h infusion, six tumour biopsies were obtained from four patients. FAA tumour concentrations were determined by HPLC and compared with subcutaneous murine solid tumours within the same analytical laboratory. Tumour/plasma percentages (range 26-61%; mean +/- SD, 43.9 +/- 11.4%) were similar to those in mice, as was the area under the curve (AUC) extrapolated to infinity and the AUC above the putative activity threshold of 100 micrograms ml-1. We conclude that the exposure of drug-refractory human melanoma tissue to FAA was comparable to that of sensitive mouse tumours. This suggests that reduced penetration of FAA into human tumours is unlikely to explain the lack of antitumour activity observed in clinical studies and that differences in mechanism of action are predominant. PMID- 1520598 TI - Cancer mortality in the first degree relatives of young breast cancer patients. AB - In a retrospective cohort study, the mothers and sisters of 740 breast cancer patients aged under 36 at diagnosis have been studied for mortality and cancer incidence. Significantly increased breast cancer mortality was observed below age 60 (30 deaths; SMR = 3.4), but not at older ages (four deaths; SMR = 0.9). The cumulative breast cancer incidence in the relatives was 3.6% by age 50, 7.6% by age 60 and 11.6% by age 70. They also suffered excess mortality below age 60 for cancers of reproductive sites (cervix, ovary and endometrium; 15 deaths; SMR = 2.6) and lung (11 deaths; SMR = 3.2), but not for other sites (12 deaths; SMR = 0.9). This large population-based cohort study provides further confirmation of genetic susceptibility to breast cancer at young ages. PMID- 1520600 TI - Pseudotumor cerebri: risk factors, clinical course, prognostic criteria. AB - Eighty-five patients with the diagnosis of pseudotumor cerebri were retro- and prospectively studied. For clinical evaluation, the following criteria were used: neurological--headache, ophthalmological--visual acuity, visual field, ophthalmoscopy and psychic--memory. Each patient was assigned 2 categories of results expressed by: neuropsychic and ophthalmological scores which were statistically processed. The following conclusions related to the aim of our paper can be drawn: I. RISK FACTORS: pregnancy (8% of cases), obesity (15%), generalized infections or located in the pelvic region+operated on (6%), hormonal treatment (cortisol (12%), estrogens (6%)); II. The clinical course was significantly favourable for: headache (51% of cases), defects of visual acuity (54%) and papilledema (63%). The long-lasting effects of the treatment applied showed: recovery (for the 2 parameters) in 27% of patients and improvement with sequelae for one and/or the other parameter in 73% of the cases; III. Among the more significant prognostic criteria were the ophthalmological symptoms and signs at onset of the disease. The ophthalmological sequelae (visual acuity, visual field defects, chronic papilledema and optic atrophy) are important factors in the prognosis of the disease and represent predictors for the surgical management. PMID- 1520599 TI - Localised lymphoma of bone: prognostic factors and treatment recommendations. The Princess Margaret Hospital Lymphoma Group. AB - Twenty seven adult patients with newly diagnosed non-Hodgkin's lymphoma localised to either bone (Stage IE) or bone and regional lymph nodes (Stage IIE) were treated between 1967 and 1988. Median age was 53 years and the commonest histology (21 patients) was diffuse histiocytic lymphoma. Twenty-four patients were treated radically: 15 with radiation therapy (XRT) alone and nine with chemotherapy plus radiation therapy (CMT). The cause specific survival for these patients was 56% at 5 years and 40% at 10 years. Survival was significantly better for patients treated by CMT (88% at 5 years) as compared to XRT alone (40% at 5 years, P = 0.03) and for age less than 60 (72% at 5 years) compared to greater than or equal to 60 (30% at 5 years, P = 0.018). Relapse-free rate was 27% at 5 years with XRT alone and 89% with CMT (P = 0.01). Risk factors for loco regional relapse (seven cases) included: large tumour bulk, treatment by XRT alone and use of 'limited' radiation fields. No radiation dose-response relationship could be identified in this study. Long term local control and survival for localised lymphoma of bone were excellent after treatment by CMT but XRT alone was associated with unacceptably high local and distant failure rates. PMID- 1520602 TI - Psychopathologic characteristics of the presuicidal syndrome. AB - The presuicidal syndrome (PS) is presented in this study with its prodromal symptoms which usually foresee suicide. One hundred patients with a PS were investigated taking into consideration all specific risk factors. Three stages of PS were outlined: psychic charging, marginal situation (Grenze-Situation) and psychic discharge. Interpretation of PS places it at the border between the clinical psychiatric fields and the ontological problems of humanity and leads to the understanding not only of the morbid psychic phenomenon in general and of the suicide in particular, but also to the major reasons of the human being who is trapped critical circumstances. PMID- 1520601 TI - Head injuries with temporal lobe compression. AB - The present study is based on the evolution of 219 cases of temporal compressive craniocerebral trauma admitted to the neurotraumatology department between 1985 and 1990. Correlations are made between the accident-operation time interval and the results obtained. Special emphasis is laid on the paraclinical methods used to make an accurate and complete diagnosis, of which computerized tomography is the most reliable for head injuries. The most frequent compressive lesions found in this series were the indirect cerebral lacerations. Their approach was done by a trephine opening aimed at the anterior 1/3 of the temporal lobe, in its basal part. The prognosis depends on the state of consciousness (patients in deep coma had small chances for survival) and on the time interval between accident and surgery, a rapid and adequately equipped transport of the patient being also of utmost importance. PMID- 1520603 TI - Communicative and cognitive functions of language behaviour. PMID- 1520604 TI - Lidocaine kindling does not generate epilepsy. AB - Forty Wistar rats were injected with a solution of lidocaine (90 mg/kg s.c.) 5 days per week for 30-40 days. In 36 of the animals, attacks of stiffness were obtained. After a period of disordered movements, the animals, remained completely immobile with the hindlimbs rigidly extended. The attacks of stiffness lasted from 10 to 60 minutes. The hemisection of the spinal cord at the thoracic level suppressed the rigidity of the ipsilateral leg. Electrical recording with electrodes applied to the cortex or implanted in the depth of the temporal lobe failed to reveal paroxysmal activity. These data could not confirm the results of other authors reporting typical epileptic seizures after lidocaine kindling. Despite essential differences, epileptic kindling and lidocaine-kindled stiffness attacks are both manifestations of the central nervous system plasticity. Therefore it appears that pharmacologically induced plasticity is a more general process than epileptic kindling. PMID- 1520605 TI - Melodic intonation in the rehabilitation of Romanian aphasics with bucco-lingual apraxia. AB - The main objective of the present study was to assess the efficiency of the melodic intonation therapy (MIT) in the rehabilitation of Romanian aphasics. Eighty predominantly Broca aphasics used the melodic intonation therapy when no other therapy methods were very efficient. The speech therapist intonated the respective word, then together with the patient and finally let him continue alone. The control group counted 80 aphasics and it applied other therapy methods. Each patient, regardless of the group, was tested twice, before and after therapy. Since most of the patients displayed severe language disorders, and other therapy methods failed in rehabilitating them, MIT was considered an efficient method in the early stages of Broca aphasia with bucco-lingual apraxia. PMID- 1520606 TI - New insights into the regulation of megakaryocytopoiesis by haematopoietic and fibroblastic growth factors and transforming growth factor beta 1. AB - Effects of cytokines on murine megakaryocyte (MK) colony formation from either unfractionated marrow cells or purified early haematopoietic cells were studied. Recombinant interleukin-3 (IL3), interleukin-6 (IL6), granulocyte-macrophage colony-stimulating factor (GM-CSF), erythropoietin (Epo) and acidic and basic fibroblast growth factor (aFGF and bFGF) each was able to stimulate MK colony growth although they varied somewhat in their potential. IL6 and FGFs, in addition to their effect on MK colony growth, increased the size of individual MK. The combination of IL3 with IL6 or FGF resulted in an additive action. Monoclonal anti-IL6 antibody completely neutralized the activity of mouse IL6 and FGFs but had no effect on human IL6, mouse IL3 and GM-CSF. When using purified lineage negative marrow cells, only IL3 and IL6 promoted MK colony formation. Transforming growth factor beta 1 (TGF-beta 1) at 10-200 pg/ml selectively inhibited IL3-induced MK colony formation, and at 0.2-0.5 ng/ml it still had no obvious effect on the activity of IL6 or GM-CSF but caused an inhibition of FGF induced MK colony formation. These data suggest that differential mechanisms are involved in the regulation of megakaryocytopoiesis by IL3, IL6, FGFs and GM-CSF, and that TGF-beta 1 negatively regulates MK development mainly by interfering with the action of IL3. PMID- 1520607 TI - A PCR-based strategy to detect the common severe determinants of alpha thalassaemia. AB - A rapid and inexpensive polymerase chain reaction (PCR) based strategy is described which detects the three common, severe alpha thalassaemia determinants observed in southeast Asia (--SEA) and the Mediterranean (--MED and (alpha)20.5). Oligonucleotide primers have been chosen which allow specific identification of both normal (alpha alpha) and abnormal (--) chromosomes using identical conditions in either the same or parallel PCR reactions. This strategy should be useful in the development of screening programmes to identify carriers of alpha thalassaemia (--/alpha alpha) and prenatal diagnosis of the Hb Bart's hydrops fetalis syndrome (--/--) for those populations in which this represents a major cause of perinatal death. PMID- 1520608 TI - Incidence of AIDS in HIV-1 infected thalassaemia patients. European and Mediterranean W.H.O. Working Group on Haemoglobinopathies and Cooleycare. AB - To estimate the cumulative incidence of acquired immunodeficiency syndrome (AIDS) in thalassaemia major patients (TMP) human immunodeficiency virus (HIV-1) infected through transfusion, 79 seropositive TMP were studied. At inclusion, mean age was 12.4 +/- 6.6 years; 40 were men; 21 were splenectomized. Centers for Disease Control, 1986 (CDC) stages and prescription of zidovudine were noted at least once a year. Cumulative incidence of AIDS and standard error were calculated using non parametric life table method. Age, sex, acute infection and splenectomy associations with progression to AIDS were tested using Breslow statistic. The median follow-up period was 4 years 11 months. At the end of the study period, 43 TMP were in CDC stage II, 23 in CDC stage III and 13 in CDC stage IV, including seven AIDS cases, of whom three had died. Four subjects died of other causes. Only two patients were treated with AZT prior to the occurrence of AIDS. Rate of progression to AIDS was not associated with acute infection, splenectomy, age, or sex. A cumulative AIDS incidence rate of 1.4% (SE 1.3%) was observed at 3 years and of 9% (SE 4%) at 5 years. PMID- 1520609 TI - Development of a monoclonal antibody capable of differentiating platelet PLA1/PLA1, PLA1/PLA2 and PLA2/PLA2 genotypes. AB - A monoclonal antibody, LK-4, has been developed which distinguishes platelet PLA1/PLA1, PLA1/PLA2 and PLA2/PLA2 genotypes on platelet glycoprotein GPIIIa of Triton-solubilized platelet extracts. An ELISA assay has been developed which traps GPIIIa with Concanavalin A, enriching the platelet extract for the PLA antigens. A second monoclonal antibody, DEK-10, which reacts equally with GPIIIa of PLA1/PLA1 and PLA2/PLA2 platelet extracts is employed as an internal standard to correct for individual differences in GPIIIa content, GPIIIa extracted by Triton X-100 and GPIIIa trapped with Concanavalin A. This ELISA assay clearly differentiated 11 different PLA1/PLA1 subjects from eight PLA2/PLA2 women with a history of neonatal alloimmune thrombocytopenia as well as six unrelated obligate heterozygotes and should be useful in evaluating the PLA genotype of pregnant women and their families. PMID- 1520610 TI - Evaluation of erythropoiesis after bone marrow transplantation: quantitative reticulocyte counting. AB - Erythroid regeneration is an important and separate element in the engraftment process in allogeneic and autologous bone marrow transplantation (alloBMT, autoBMT). Qualitative visual reticulocyte counting has proved inadequate in the evaluation of erythropoiesis after BMT but automated flow cytometry now allows the reliable quantitation of reticulocytes even to very low levels. Reticulocyte counts and highly fluorescent reticulocyte (HFR) counts (very early reticulocytes) were estimated daily in recipients of 22 autoBMT and 14 alloBMT using a Sysmex R-1000 automated reticulocyte counter. Marrow ablation caused an immediate and rapid fall in both the reticulocyte count and the HFR. Measurable numbers of reticulocytes persisted throughout the hypoplastic period, but HFR fell to zero in the majority of both the autoBMT and alloBMT. HFR rose significantly after a median time of 14 d post-autoBMT, and 12 d post-alloBMT. Attainment of 15 x 10(9)/l reticulocytes and 0.5 x 10(9)/l HFR at day 21 post transplant was associated with ultimate engraftment in 100% cases. Inadequate engraftment was seen in the majority of patients whose responses fell below these levels. Graft-versus-host disease was associated with a transient slight reduction in reticulocyte count. Neither episodes of infection nor blood transfusions had any significant impact on trends of reticulocytes or HFR. Automated flow cytometric reticulocyte counting has been shown to provide an accessible measure of erythroid activity which may be of predictive value in the management of patients following bone marrow transplantation. PMID- 1520611 TI - Gamma heavy chain disease developing in association with myelodysplastic syndrome. PMID- 1520612 TI - High prevalence of the beta-thalassaemia nonsense 37 mutation in Catalonians from the Ebro delta. PMID- 1520613 TI - Treatment of severe aplastic anaemia with total lymphoid irradiation and methylprednisolone. PMID- 1520614 TI - Ring eosinophils in hypereosinophilic syndrome. PMID- 1520615 TI - Hepatitis C antibody profile in adults with haemophilia and their sexual partners. PMID- 1520616 TI - Treatment of alloimmunized, thrombocytopenic patient with acid-treated random donor platelets. PMID- 1520617 TI - Oral megadose methylprednisolone for treatment of Diamond-Blackfan anaemia. PMID- 1520618 TI - Effect of pH on binding of B12 to IF and R-protein. PMID- 1520619 TI - Molecular analysis of clonality in plasma cell dyscrasias. AB - It has been suggested that multiple myeloma, generally considered a neoplastic disorder of mature plasma cells, may arise from a pluripotent haemopoietic stem cell. The possibility that circulating lymphocytes derive from the same neoplastic progenitor has been tested in a large number of studies in the past few years, as proof of the interest that this subject is raising among scientists, and also of its elusiveness. We studied a group of 29 patients with plasma cell dyscrasias in order to evaluate clonality of haemopoietic cell populations. The X-linked markers hypoxantine phosphoribosyltransferase (HPRT) and phosphoglycerate kinase (PGK) disclosed no monoclonal component in seven heterozygous women. Analysis of immunoglobulin gene rearrangement with four probes showed a germline configuration in samples from 25/29 patients. Only four bone marrow samples from subjects with aggressive disease had rearranged C mu sequence; one had rearrangement of JH and C mu. PMID- 1520620 TI - Lymphocytes from multi-transfused patients exhibit cytotoxicity against autologous cells. AB - We previously demonstrated that multitransfused patients with severe aplastic anaemia (SAA) exhibit high numbers of alloreactive cytotoxic T lymphocyte precursors directed against their HLA identical siblings. In this study a group of patients who had received multiple blood transfusions for SAA, other haematological diseases or acute blood loss were tested for autocytotoxicity and the results compared with those of untransfused controls. These controls consisted of normal individuals, patients with chronic myeloid leukaemia (CML) or untransfused patients with SAA. There was a significantly higher degree of autocytotoxicity in multitransfused patients, than in the untransfused controls, including untransfused patients with SAA (P = 0.0001). These results suggest that blood transfusion is responsible for inducing autoreactivity. In one patient, in whom both alloreactive anti-non-MHC and autoreactive cytotoxic T lymphocytes (CTL) had been detected, it was demonstrated that there was no crossreactivity between the alloreactive and autoreactive CTL responses. Inhibition studies using monoclonal antibodies revealed the effector cells to be T lymphocytes and the restricting determinants to be both HLA class I and II molecules. PMID- 1520621 TI - Epidermolysis bullosa acquisita induced by GM-CSF: a role for eosinophils in treatment-related toxicity. AB - A patient treated with granulocyte-macrophage colony-stimulating factor (GM-CSF) developed eosinophilia and epidermolysis bullosa acquisita. The bullae were subepidermal, and filled with an inflammatory infiltrate composed predominantly of eosinophils. Immunofluorescence studies disclosed linear deposition of IgG, IgA and C3 at the basement membrane zone and immunoelectron microscopy demonstrated antibody deposition in the lamina densa and sublamina densa region; however, the patient's serum did not contain circulating antibody to basement membrane zone antigens. Staining with monoclonal antibodies revealed dense deposits of both eosinophil peroxidase and eosinophil major basic protein at the dermal-epidermal junction. The eosinophilia and skin lesions resolved upon discontinuation of GM-CSF. This case provides evidence for two hypotheses: (1) GM CSF induced proliferation and activation of eosinophils may contribute to some of the toxicities of GM-CSF treatment, and (2) activated granulocytes, including eosinophils, may mediate blister formation in epidermolysis bullosa acquisita. PMID- 1520622 TI - Remission with morphological myelodysplasia in de novo acute myeloid leukaemia: implications for early relapse. AB - Myelodysplastic features of remission bone marrow were investigated in 46 adults with de novo acute myeloid leukaemia (AML) according to the FAB morphological criteria for myelodysplastic syndromes (MDS). Compared with a group of 18 patients with the common type of acute lymphoblastic leukaemia in remission, micromegakaryocytes (30.4% v. 5.6%, P less than 0.05), multi-separated nuclear megakaryocytes (45.7% v. 0%, P less than 0.01), degranulated neutrophils (39.1% v. 5.6%, P less than 0.05), and neutrophils with hyposegmented nuclei (34.8% v. 0%, P less than 0.01) were significantly more common in the AML patients. In contrast, dyserythropoietic changes had a similar incidence in both groups. When compared with the clinical features at initial diagnosis in AML cases, the dysmegakaryocytic changes in remission marrow were found to be significantly more frequent in patients with monocytic involvement (mainly M4) or trilineage myelodysplasia (T-MDS AML). Disease-free survival was significantly shorter in patients with micromegakaryocytes (P less than 0.05) or neutrophils with hypogsegmented nuclei (P less than 0.05) than in those without these features. Overall survival was also significantly shorter in patients with micromegakaryocytes (P less than 0.05). These findings may help in developing new strategies for the post-remission therapy of AML, and also suggest that myelodysplastic changes in the remission marrow of de novo AML patients may be related to haematopoietic recovery by a preleukaemic clone which eventually leads to early leukaemic relapse. Dysplastic marrow, however, was not necessarily associated with peripheral pancytopenia in the present series, warranting basic research on such putative clonal remissions. PMID- 1520623 TI - Immunophenotypic subclassification of chronic lymphocytic leukaemia (CLL). AB - To determine the significance of the immunophenotypic heterogeneity of B-cell chronic lymphocytic leukaemia (CLL), surface immunoglobulins (SIgs), mouse rosette assays (MR), and a panel of monoclonal antibodies for B cells, T cells and myeloid cells were performed on peripheral blood samples from 61 newly diagnosed cases. Four groups were observed: group I (SIg+, MR+, CD19/20+, CD5+, T antigen (Ag)-; 27 cases); group II (SIg+, MR+, CD19/20+, CD5+, T Ag+; 17 cases); group III (SIg+, MR+ CD19/20+, CD5-, T AG-; 12 cases); and group IV (SIg-, MR+, CD19/20+, Cd5+, T Ag-; 5 cases). Groups were compared according to French American-British Cooperative Group subtypes, clinical and laboratory features, Rai staging, and survival. Typical CLL morphology (greater than 90% small lymphocytes) was present in 20/20 (100%) of group I cases and 23/27 (85%) group II, III and IV cases (P = 0.09). Expression of a myeloid antigen was seen in 5/27 group I cases (18%) and 1/16 group II cases (6%), but was not predictive of survival (P = 0.36). The CD5- group III had a lower haemoglobin level (P less than 0.0001), higher Rai stage (P less than 0.002), and poorer survival at 5 years (P less than 0.02) than the other groups. We conclude that at least four distinct immunophenotypic subgroups of B-cell CLL can be determined. Expression of myeloid or T-cell antigens does not appear to predict for patient survival; however, lack of CD5 antigen may be associated with more advanced stage of disease and poor patient survival. PMID- 1520624 TI - Cytomorphology of childhood lymphoblastic leukaemia: a prospective study of 2000 patients. United Kingdom Medical Research Council's Working Party on Childhood Leukaemia. AB - Blast cell morphology of children with lymphoblastic leukaemia (ALL) entering two national multicentre trials was prospectively reviewed by three haematologists to define the clinical importance of (a) French-American-British (FAB) classification, (b) the presence of cytoplasmic vacuoles, and (c) the presence of 'hand-mirror' cells. Of 2135 evaluable children, 1907 (89%) had FAB L1 morphology and 228 (11%) L2. (L3 patients were not eligible for the trials in question). L2 patients more frequently had residual disease 14 d after starting treatment and had a significantly inferior disease-free survival, but not if the analysis was stratified for age, sex and diagnostic white cell count (WBC). 627 (29%) had blast cells with cytoplasmic vacuoles, and showed a significant survival advantage over the remainder. Vacuoles were positively associated with a low WBC, age range 1-6 years and blast cell positivity for CD10, but their benign influence was apparent even when these variables were taken into account. 'Hand mirror' (HM) cells were only studied in UKALL X, and were noted in 316/1402 (23%) children. There appeared to be an inverse correlation between HM cells and cytoplasmic vacuoles and a weak association with T-cell immunophenotype, but no prognostic significance was evident. FAB classification appears to be of less prognostic importance than has previously been supposed, though L2 disease is more resistant to current remission induction regimens. Hand-mirror cells may be more common in T-ALL, but are seen in all types and are not related to prognosis. Cytoplasmic vacuoles are predictive of a good response to current therapeutic schedules even allowing for other prognostic variables, and are the single most important morphological feature relating to prognosis in childhood ALL. PMID- 1520625 TI - Comparison of chromosome analysis and BCL-1 rearrangement in a series of patients with multiple myeloma. AB - Translocation (11;14)(q13;q32) is a recurring chromosome abnormality which is found non-randomly in non-Hodgkin's lymphoma, especially of follicular type, as well as in B-cell chronic lymphocytic leukaemia, Waldenstrom's macroglobulinaemia and multiple myeloma. To define further the prevalence of this abnormality in multiple myeloma, we studied a series of 17 patients with this disease with concomitant chromosome analysis and Southern blotting, using a probe specific for the major translocation cluster of the BCL-1 oncogene which is located at chromosome 11q13. Karyotype analysis of 14 evaluable patients revealed three cases with abnormalities of chromosome 11q13, two of them with t(11;14)(q13;q32) and one with del (11)(q13). Southern blot analysis showed no rearrangements in BclI and HindIII digests of DNA from 17 patients including the three patients with anomaly of chromosome 11q13, using a BCL-1 specific probe. A possible restriction length polymorphism was detected in EcoRI cut DNA of five out of 11 patients studied. Therefore the chromosomal break point in our cases with abnormality of chromosome 11q13 must lie outside the major translocation cluster of the BCL-1 gene. However, in centrocytic lymphoma rearrangement of the BCL-1 oncogene has been detected in up to 50% of cases. Location of the break point may therefore be dependent on the differentiation of the transformed B-cell. PMID- 1520626 TI - Interleukin-4 and nerve growth factor can act as cofactors for interleukin-3 induced histamine production in human umbilical cord blood cells in serum-free culture. AB - In order to better define the role of recombinant interleukins and growth factors in supporting histamine production by histamine-producing-cells (HPC), namely basophils or mast cells, we have conducted experiments in which we compared the abilities of IL-3, IL-4, IL-6 and nerve growth factor (NGF), either alone or in various combinations, to stimulate histamine production from human umbilical cord blood mononuclear cells cultured in either the presence or absence of serum. Over a period of 15 d, IL-3 was able to support intracellular histamine production, in both serum-supplemented and serum-free medium, although the effectiveness of IL-3 was lower in the serum-free cultures. IL-4, NGF and IL-6 taken individually, exhibited little, if any, histamine-promoting activity regardless of whether or not the cells were cultured in serum. Moreover, none of these cytokines significantly enhanced the effect of IL-3 in serum-supplemented cultures. In contrast, IL-3-promoted histamine production in serum-free cultures was significantly enhanced by IL-4 and NGF. These results demonstrate that both IL-4 and NGF can function as cofactors with IL-3 in the support of histamine production in human umbilical cord blood cells. PMID- 1520627 TI - Myelodysplastic syndrome (MDS)-associated inhibitory activity on haematopoietic progenitor cells: contribution of monocyte-derived lipid containing macrophages (MDLM). AB - We studied myelodysplastic syndrome-associated inhibitory activity (MDS-IA), which inhibited colony formation in vitro of normal granulocyte-macrophage progenitors (CFU-GM). When adherent marrow cells were incubated with fetal calf serum for 21-24 d, monocyte-derived lipid containing huge macrophages (MDLM) developed. MDLM from MDS marrow (MDS-MDLMs) and their conditioned medium (MDLM CM) consistently suppressed the growth of normal CFU-GM colony formation. MDS-IA was active on CFU-GM during the S-phase and relatively resistant to heating. Monoclonal antibody against H subunit (acidic) ferritin and polyclonal antibody against placental ferritin neutralized the inhibitory activity of MDS-MDLMs. In addition, cell lysates of MDS-MDLMs reacted to both monoclonal anti-H subunit ferritin and polyclonal anti-placental ferritin in Western blotting analysis, indicating that the inhibitory activity was predominantly acidic isoferritin. On the other hand, MDLMs obtained from normal bone marrow had a CFU-GM enhancing activity. These results suggest that MDS-MDLMs may be responsible for the suppression of granulopoiesis in patients with MDS and that the suppression may be mediated by soluble factors, notably H subunit isoferritin. PMID- 1520628 TI - Ultraviolet irradiation modulates MHC-alloreactive cytotoxic T-cell precursors involved in the onset of graft-versus-host disease. AB - Ultraviolet B (UVB) irradiation of cellular blood components has been proposed as a new technology to prevent HLA sensitization in recipients. Earlier studies have shown that a dose of 2 J/cm2 abrogates the ability of lymphocytes to serve as stimulators in mixed lymphocyte cultures (MLC). In this study we have evaluated the effect of UV energy on T-lymphocytes for the prevention of transfusion associated graft-versus-host disease (TA-GvHD). The response of cytotoxic T lymphocyte precursors against host alloantigens was almost undetectable at a dose of 0.5 J/cm2. T-cell proliferation in MLC or in response to phytohaemagglutinin was inhibited by more than 95% at doses of 1 J/cm2 or higher. The data suggest that UV irradiation can be used to prevent both HLA sensitization and TA-GvHD in recipients. PMID- 1520629 TI - Philadelphia positive acute leukaemia with minor breakpoint cluster rearrangement may be a stem cell disease. AB - The biology of Philadelphia chromosome positive (Ph+) acute lymphoblastic leukaemia (ALL) is the subject of much interest. We present a case of Ph+ ALL with a minor breakpoint cluster (mBCR) rearrangement who subsequently relapsed with Ph+ mBCR+ acute myeloid leukaemia and later with Ph+ mBCR+ acute stem cell leukaemia. This case provides further evidence that Ph+ ALL with a mBCR rearrangement may arise from a pluripotent stem cell with similar potential to that of chronic granulocytic leukaemia to undergo blastic crises with differing lineage characteristics. PMID- 1520630 TI - Specific binding between human neutrophils and heparin. AB - Heparin binding on polymorphonuclear leucocytes (PMNL) was characterized. Heparin binding was specific, rapid, saturable and reversible. One single class of heparin binding sites was found with a dissociation constant of 1.22 mumol/l and 7.7 x 10(6) sites per PMNL. The binding was independent of the anticoagulant activity of heparin. Heparin affinity chromatography on radio-iodinated cell lysates followed by polyacrylamide gel electrophoresis in the presence of sodium dodecylsulphate revealed a 130 kD heparin binding protein. Heparin binding was inhibited by disodium salt of ethylenediamine tetraacetic acid. Cell surface bound heparin was functionally inactive and did not affect the inactivation of thrombin by antithrombin III. Our study demonstrates that heparin interacts with PMNL by a cell-surface binding protein. These instructions could be consistent with the modifications of some PMNL functional properties in the presence of heparin. PMID- 1520631 TI - A family with haemolytic anaemia and three beta-globins: the deletion in haemoglobin Atlanta-Coventry (beta 75 Leu----Pro, 141 Leu deleted) is not present at the nucleotide level. AB - Analyses of haemoglobin from a family with an unstable haemoglobin haemolytic anaemia demonstrated that the affected individuals had three beta-globins, namely, normal (beta A), Atlanta (beta At) with a mutation of beta 75 Leu----Pro, and beta-Atlanta-Coventry (beta At-Co) with mutation of beta 75 Leu----Pro and beta 141 Leu deleted. These were present in the ratio 66:23:11 respectively. The structure of the beta-globin cluster, however, was found to be normal by Southern blotting; also cytogenetic analysis failed to show any abnormality. DNA sequence analyses demonstrated the presence of the beta At mutation in genomic DNA isolated from leucocytes but the Coventry deletion of 141 Leu in beta At-Co was not present in genomic DNA. PCR amplification of the beta-globin cDNA and direct sequencing of the product also failed to demonstrate the Coventry deletion. Thus, it appears that the absence of 141 Leu in the beta At-Co globin is a consequence of the beta At mutation in these patients and that both beta At and beta At-Co are the product of a single gene. This unusual conclusion is paralleled in the bizarre case of Hb Vicksburg where the deletion of a leucine at beta 75 is not coded for in genomic DNA. PMID- 1520632 TI - Beta 141 Leu is not deleted in the unstable haemoglobin Atlanta-Coventry but is replaced by a novel amino acid of mass 129 daltons. AB - Reinvestigation of the structure of the beta-chain of Hb Atlanta-Coventry (beta 75 Leu----Pro, beta 141 Leu deleted) confirmed the presence of two abnormalities; however, analysis of the aberrant beta Co14 tryptic peptide by liquid secondary ion mass spectrometry indicated that the beta 141 Leu (mass 113 daltons) was not deleted but replaced by a novel amino acid of mass 129 daltons. The new amino acid in peptide beta Co14 was uncharged at pH 6.5, more hydrophillic than leucine and susceptible to cleavage by both chymotrypsin and carboxypeptidase A. We propose that the new residue is likely to be hydroxyleucine and that it results from post-translational oxidation of beta 141 Leu as a consequence of perturbation of the haem environment caused by the beta 75 Leu----Pro mutation in the E helix (E19). This proposal is entirely consistent with recent DNA analysis which showed that beta At-Co was not the product of a third beta-globin gene and that neither of the two beta-globin genes, beta A nor beta Atlanta, contained a deletion of the beta 141 Leu codon. We have subsequently found this modified amino acid at position beta 141 in two other unstable haemoglobins, both of which involve mutations on the haem side of the E helix. PMID- 1520633 TI - A rapid solid-phase extraction and HPLC/DAD procedure for the simultaneous determination and quantification of different benzodiazepines in serum, blood and post-mortem blood. AB - A rapid and quantitative method for the determination of benzodiazepines using high-performance liquid chromatography (HPLC) with diode-array detection (DAD) is reported. The drugs were extracted from serum, blood or post-mortem blood using C18 extraction columns. Brotizolam was used as internal standard. Experiments with spiked serum/blood samples resulted in recoveries between 75% and 94% for all investigated benzodiazepines. Excellent linearity was obtained over the concentration range 5-1500 ng benzodiazepine/ml. The limit of detection was approximately 2 ng/ml. The detection of low therapeutic serum levels of highly potent benzodiazepines is also possible. PMID- 1520634 TI - The elimination kinetics of methanol and the influence of ethanol. AB - Four male subjects aged between 20 and 29 years were given intravenous injections of methanol at a dosage of 10 mg per kg body weight, once without prior administration of ethanol, and once after oral ingestion of 0.3 g ethanol per kg body weight. The serum methanol concentration was monitored over the next 5 h (after methanol administration alone) and 6-7 h (after methanol administration following ethanol ingestion). The elimination of methanol administered alone was found to follow first-order kinetics with a rate constant for the elimination phase of 0.475-0.259 h-1, corresponding to an elimination half-life of 1.8-3.0 h. When ethanol was also administered methanol oxidation was found to be completely blocked until the blood ethanol concentration had fallen to 0.2 g/kg. When the ethanol concentration had dropped to zero, methanol elimination followed exactly the same course as that observed in the experiment without prior administration of ethanol (k: 0.378-0.231 h-1; t1/2: 1.5-2.7 h). PMID- 1520635 TI - The screening for common drugs of abuse in whole blood by means of EMIT-ETS and FPIA-ADx urine immunoassays. AB - The purpose of the paper was to compare the performance of ETS (EMIT) and ADx (FPIA) analyzers for screening blood samples for drugs of abuse after 2 alternative pretreatment procedures (acetone precipitation and ultrafiltration). Cannabinoids, benzodiazepines and benzoylecgonine were not detectable with both assays after ultrafiltration. The detectability of morphine in blood ultrafiltrates was distinctly lower than after acetone precipitation. The comparison of results obtained with ETS and ADx after acetone precipitation showed that ETS assay is slightly more sensitive but ADx is slightly more reproducible. Both assays may be used for blood examination with similar cut-off values. The ETS analyzer gave much better analytical performance (speed, flexibility) and lower reagent costs than the ADx analyzer. PMID- 1520636 TI - Lethal myocardial infarction subsequent to compression of the left anterior descending coronary artery induced by traumatic hematoma. AB - Post-traumatic myocardial infarction is a well-known although rare complication of blunt chest traumas. In cases of proximally located damage to the coronary arteries, modern vascular surgery such as bypass operations may be lifesaving. In this paper we describe a case, where a healthy 35-year-old man developed a lethal myocardial infarction 8 days after a chest trauma caused by a moped. The ECG obtained 4 h after the accident showed extensive transmural ischemia of the anterior wall. At autopsy a hematoma originating from a side branch was found to compress the left anterior descending coronary artery immediately distal to its origin from the main stem. This finding suggests that bypass surgery could have saved the life of this young man. Patients with evidence of myocardial ischemia following chest traumas should be transferred to a cardiac center as early as possible. PMID- 1520637 TI - Evaluation of sperm specific lactate dehydrogenase isoenzyme C4 (LDH C4)- application to semen detection in stains. AB - The usefulness of LDH C (or LDH X) as a semen-specific marker has been tested. Many different methods have been applied for identification using various electrophoretic methods such as agarose gel electrophoresis, IEF, rocket immunoelectrophoresis with subsequent enzymatical, immunological and immunochemical detection methods. Further methods applied were dot blot analysis for LDH C and PCR analysis for X/Y-chromosome differentiation. In blood/semen mixtures the LDH C-bands were detectable in dilutions up to 50-fold after staining for total LDH activity. An appropriate extraction procedure was developed. Immunological tests using a polyclonal antibody against LDH C were found to be highly specific and highly sensitive. The immunological test gave positive results with azoospermic stains up to a few weeks and in normal sperm stains positive reactions were obtained even after 8 months storage. A comparison of different detection methods for semen showed that immunological detection methods for LDH C are, at least after longer time periods of storage, superior to microscopical detection. Swabs showed positive LDH C-reactions up to 48 h after intercourse. This reaction was closely correlated to PCR for male cells and to microscopical searching. PMID- 1520638 TI - Interpretation of COHb concentrations in the left and right heart blood of cadavers. AB - Carbon monoxide hemoglobin (COHb) concentrations in left and right heart blood samples from cadavers both exposed and not exposed to fire or CO gas were analyzed by the gas chromatographic method. The COHb concentration ratio between samples of left and right heart blood (L/R ratio) does not appear to be useful for establishing whether death has occurred before or after exposure to fire with the exception of cases where no soot can be detected in the airways by the naked eye and the COHb concentration in the blood sample is within the level considered normal for tobacco smokers. PMID- 1520639 TI - Nerve conduction as a means of estimating early post-mortem interval. AB - Methods in current practice for ascertaining time of death are largely based on the cooling of the body after death and are somewhat unreliable. A theoretical relationship is known to exist between the decline in the properties defining nerve conduction and time after death caused by the gradual cessation of metabolic activity in nerves. A number of such properties were measured in rats during life and after death. In most cases the relationship was found to be inconsistent. The chronaxie of the strength duration curve for the sciatic nerve was, however, found to increase consistently and reproducibly in a linear fashion over the first 90 min after death to a plateau value which was maintained beyond 135 min. These findings are discussed as the possible basis of a forensic method of determining the duration of the "post mortem interval" within the first few hours after death. PMID- 1520641 TI - Genetic polymorphism of human alpha 2 HS-glycoprotein (AHSG) in the resident population of the Basque Country (northern Spain). AB - The genetic polymorphism of human alpha 2 HS-glycoprotein (AHSG) was studied in a sample of 466 healthy unrelated individuals resident in the Basque Country (Northern Spain) by isoelectric focusing on micro-ultrathin polyacrylamide gels followed by immunoblotting. The allele frequencies obtained were AHSG*1 = 0.7253, AHSG*2 = 0.2683 and AHSG*3 = 0.0064. These allele frequencies were compared with those reported in other European populations. PMID- 1520640 TI - ABH-related antigens in human male genital tract. A histochemical examination. AB - The localization of ABH related antigens in human male reproductive tract was examined using monoclonal antibodies and an avidin biotin complex method. No positive reaction with blood group antibodies on spermatozoa was observed in testis and ductus epididymidis apart from erythrocytes and endothelial cells. The expression of ABH and ABH related antigens in ductuli efferents testis, ductus epididymidis, seminal vesicle and prostate was complexly coded by a combination of H, Se, Le and X genes. The results obtained in this study indicate that the ABH antigens detected on spermatozoa of seminal stains are coating antigens and not inherent to the cell membrane, and the ABO, H, Se, Le and X genes are subjected to a tissue-dependent differential expression. PMID- 1520642 TI - Identification of human remains by amplification and automated sequencing of mitochondrial DNA. AB - The highly decomposed remains of a corpse were identified by the amplification and direct sequencing of mitochondrial (mt) DNA. Degraded DNA was extracted from bone fragments and a necrotic skin sample and amplified at 2 hypervariable segments within the mitochondrial non-coding region using 2 rounds of nested PCR. Both strands of the amplified regions were sequenced and compared with each other to ensure fidelity of the data. Sequences from the bone and skin were found to be identical and matched data generated from a blood sample provided by a presumptive sister of the deceased. Thus, this evidence was consistent with the sister and the deceased being related. PMID- 1520643 TI - Diffusion as a mechanism of postmortem drug redistribution: an experimental study in rats. AB - In some cases of drug overdose there is a reservoir of unabsorbed drug in the stomach and gut. Furthermore, agonal aspiration might establish a second reservoir in the lungs. Two experimental rat models were used to study if diffusion from these reservoirs could contribute to the phenomenon of postmortem drug redistribution. Overnight fasted rats were sacrificed by CO2 and 75 mg of amitriptyline (AMI) was administered by a gastric tube. In the first series (n = 19), the tubes were removed after AMI administration. In the second series (n = 17), the trachea was ligated and cut prior to drug administration to prevent airways contamination. The rats were left at room temperature on their back for a period of 5, 10, 24, 48, 96 up to 192 h and samples of heart blood, blood from the inferior vena cava, tissue samples from heart, lungs, different liver lobes, kidney and psoas muscle were taken. In both series of rats we observed that as early as 5 h postmortem increasing concentrations of amitriptyline were found in the liver lobes lying closest to the stomach. In rats where the trachea was not ligated, drug contamination of the lungs also resulted in an increase in drug concentration within 5 h in heart blood and heart muscle. In rats where the trachea had been ligated, amitriptyline was found in the lungs after 96 h postmortem. The main metabolite nortriptyline was also detected.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1520644 TI - The time-dependent rearrangement of the epithelial basement membrane in human skin wounds--immunohistochemical localization of collagen IV and VII. AB - In 62 human skin wounds (surgical wounds, stab wounds and lacerations after surgical treatment) we analyzed the immunohistochemical localization of collagen IV in the epithelial basement membrane. In 27 of these wounds the distribution of collagen VII, which represents a specific component of the basement membrane of stratified epithelia, was also analyzed. We were able to demonstrate a virtually identical co-distribution of both collagen IV and VII in the wound area with no significant time-dependent differences in the appearance of both collagen types. Fragments of the epithelial basement membrane could be detected in the wound area from as early as 4 days after wounding and after 8 days a complete restitution of the epithelial basement membrane was observed. In all cases with a wound age of more than 21 days the basement membrane was completely reformed over the former lesional area. The period between 8 and 21 days after wounding was characterized by a wide variability ranging from complete restitution to deposition of basement membrane fragments or total lack of the epidermal basement membrane. PMID- 1520645 TI - Time-dependent appearance of myofibroblasts in granulation tissue of human skin wounds. AB - Human skin wounds (66) inflicted between 20 h and 7 months prior to biopsy were studied. In order to identify the type of cellular differentiation of the fibroblastic cells in the granulation tissue, alpha-smooth muscle actin and desmin were immunohistochemically localized. The value of any presumed time dependent appearance and/or disappearance of positively stained cells was tested for the estimation of wound age. In skin specimens with a wound age less than 5 days (n = 15) no typical granulation tissue had developed and no alpha-actin positive myofibroblasts could be detected. The first appearance of positively reacting myofibroblasts was noted in a 5-day-old wound. In 57% of the lesions with a wound age between 5 and 31 days (25 out of 44 cases) typical granulation tissue formation was present and myofibroblasts with positive reaction for alpha smooth muscle actin could be identified. Numerous positively reacting cells could generally be found in wounds aged between 16 and 31 days, but also in wounds less than 16 days old. In 29% of the cases with a wound age of more than 31 days (2 out of 7 cases) alpha-sma-positive myofibroblasts also occurred. Fibroblastic cells positive for desmin could not be seen at all in our series. Our results demonstrate the appearance of alpha-sma-positive myofibroblasts with the initial formation of typical granulation tissue in human skin lesions as early as approximately 5 days after wounding. In contrast to recent experimental results these cells remained detectable in wounds aged more than 2 months in some cases.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1520646 TI - Prehospital thrombolysis in a rural community: short- and long-term survival. AB - In order to assess the feasibility and outcome of using prehospital thrombolysis in acute myocardial infarction in a rural community, we performed an open randomized study of patients with symptoms of acute myocardial infarction of less than 6 hours. One hundred and forty-five patients with acute myocardial infarction were allocated to receive IV streptokinase prehospital by means of a mobile coronary care unit (MCCU) (n = 43) or to receive IV streptokinase in hospital (n = 102). The mean delay time to treatment was 138 minutes (MCCU group) and 172 minutes (hospital group) (p less than 0.02). Reperfusion time was 88 minutes for the MCCU group and 92 minutes for the hospital group. Mortality at 14 days was 2.3% for the MCCU group and 11.7% for the hospital group (p less than 0.05). Six month mortality was 4.9% for the MCCU group and 17.3% for the hospital group (p = 0.03). Mortality at 1 year was 6.1% for the MCCU group and 20.0% for the hospital group (p = 0.04). There were no significant adverse events in either treatment group. Thus, prehospital thrombolysis by streptokinase is feasible and allows significant reduction in the delay time to treatment initiation. There are encouraging improvements in both short- and long-term survival with no apparent reduction in safety profile. PMID- 1520647 TI - Influence of the rt-PA dose (1 mg/kg versus 1.5 mg/kg) and duration of administration on the patency of infarct-related coronary arteries in 81 patients. AB - This open study compared the efficacy and side effects of two dose regimens of intravenous rt-PA initiated before the fifth hour after the onset of myocardial infarction. The first 40 patients (group A) received 1 mg/kg of rt-PA infused over 90 minutes, including a 10-mg initial bolus. The following 41 patients (group B) received 1.5 mg/kg (20-mg initial bolus, 60% over 60 minutes and 40% over 120 minutes). Noninvasive clinical, electrocardiographic, and biochemical parameters of reperfusion were recorded systematically, along with serial measurements of fibrinogen and hemoglobin levels. Coronary arteriography and left ventriculography were performed at the 48th hour or earlier, on an emergency basis, in the absence of signs of reperfusion, or if there were clinical and ECG signs of rethrombosis. Patency of the infarct-related artery (TIMI grades 2 and 3) was achieved in 55% of the group A patients vs. 83% of the group B patients (p less than .01). Twelve emergency coronary arteriographies were performed in each group. No significant difference was observed in the ejection fraction (48% in group A vs. 52% in group B). The peak CPK level was similar in both groups, but the peak occurred earlier in group B (p less than .001). There was no statistically significant difference between the two dose regimens in terms of reduction in fibrinogen or plasminogen levels. Two deaths occurred in group A vs. one death in group B. No cerebrovascular accidents occurred in either group.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1520648 TI - The total ischemic burden European trial (TIBET): design, methodology, and management. The TIBET Study Group. AB - TIBET is a European multicenter, double-blind parallel group trial with the main objective of investigating whether total ischemic burden has important prognostic implications in patients with stable angina on treatment. A secondary objective is to compare the antianginal and antiischemic effects of atenolol (50 mg bid), nifedipine (20-40 mg bid), and their combination using standardized exercise testing and Holter monitoring techniques. The main primary end points are cardiovascular morbidity and mortality. The secondary end points are time to onset of significant ischemia, angina on exercise stress testing, exercise capacity at onset of angina, 1-mm ST-segment depression and termination of exercise, total duration and number of significant ischemic episodes during 48 hours of Holter monitoring, and their circadian distribution. The target population, the assessments, and the management of the trial are described in detail. PMID- 1520650 TI - Effects of altered extracellular potassium and pacing cycle length on the class III antiarrhythmic actions of dofetilide (UK-68,798) in guinea-pig papillary muscle. AB - The effects of altered extracellular K+ concentrations ([K+]o) and pacing cycle lengths (CLs) on the electrophysiological actions of dofetilide (UK-68,798), a potent class III antiarrhythmic agent, were examined in isolated guinea-pig ventricular papillary muscle. At a normal [K+]o (4 mM) and at CL between 300 and 5000 msec, dofetilide (10 nM) significantly increased the action-potential duration (APD) and the effective refractory period (ERP), whereas other action potential parameters were unaffected. Elevation of [K+]o to 10 mM reduced membrane diastolic potential (MDP), action-potential amplitude (APA), and the maximum rising velocity of the action-potential upstroke (Vmax). These changes were accompanied by a small shortening of APD90, but with an increase in ERP; i.e., the ERP/APD90 ratio was increased. Dofetilide also significantly lengthened APD90 at 10 mM [K+]o and at each CL. Even at the short cycle lengths (300 and 500 msec), dofetilide-induced increases in APD90 were not attenuated whether [K+]o was at 4 or 10 mM. These results indicate that at various pacing CLs, 10 nM dofetilide increases myocardial APD and ERP to a similar extent without significant reverse use-dependence when the cell membrane is normally polarized or partially depolarized by elevated [K+]o. Dofetilide may, therefore, be expected to be beneficial in the treatment of cardiac tachyarrhythmias related or unrelated to regional myocardial hyperkalemia during myocardial ischemia. PMID- 1520649 TI - Intermittent infusion of dobutamine in the therapy of severe congestive heart failure--long-term effects and lack of tolerance. AB - Twenty patients with refractory heart failure NYHA class IV were randomly assigned to infusion therapy with 9.25 micrograms/kg/min dobutamine over 24 hours or placebo. Eight infusions over a 4-week period were performed in the hospital; between infusions breaks of 3 days were scheduled. A dose titration was performed before study during which dobutamine was infused at 2.5 micrograms/kg/min and increased by 2.5 micrograms/kg/min steps every 15 minutes up to a maximum dosage of 10 micrograms/kg/min. After dobutamine, exercise duration on the treadmill stress test increased from 177 +/- 110 seconds to 251 +/- 120 seconds (p less than 0.05). The heart-rate response to exercise increased (91 +/- 20 to 116 +/- 26 beats/min at baseline, 88 +/- 17 to 132 +/- 26 beats/min after therapy). Body weight decreased from 70.9 +/- 15.5 to 68.9 +/- 14.2 kg (p less than 0.03). On placebo, no significant changes were evident. Systolic time intervals and hemodynamic parameters showed only minor and not significant changes in both groups. No excess mortality emerged during intermittent dobutamine therapy. No clinical or hemodynamic signs of tolerance development were evident during control assessment 3 days after the last infusion. Intermittent therapy with dobutamine seems to be a promising concept in the management of refractory severe heart failure. PMID- 1520651 TI - Modified enucleation via lateral orbitotomy for choroidal melanoma with orbital extension: a report of two cases. AB - We report two cases of choroidal melanoma with massive orbital extension that were managed by modified enucleation by way of a lateral orbitotomy. In both cases, the orbital component of the tumor was removed intact along with the globe. This approach allows placement of an orbital implant and avoids the long healing process associated with orbital exenteration. PMID- 1520652 TI - Measurement of globe position in complex orbital fractures. I. A modification of Hertel's exophthalmometer, using the external auditory canal as a reference point. AB - Where there has been displacement or removal of the lateral orbital rim or zygomaticomaxillary complex secondary to trauma or surgery, the measure of globe position by the Hertel exophthalmometer is problematic and inaccurate. A modification of Hertel's instrument that uses the external auditory canal (EAC) rather than the orbital rim as reference point has been developed. Measurement of globe position of 120 normal volunteers was obtained with the Hertel and the modified EAC-fixated exophthalmometer. Although the mean absolute difference between right and left measurements for both methods (Hertel mean, 0.36 mm; modified mean, 0.51 mm; n = 120) differed statistically from 0 (p = 0.0001), that difference was not clinically significant. A more meaningful comparison was that of the variability of the two methods. The variance of the Hertel method (0.32) did not differ from the variance of the modified method (0.40; p = 0.06). No statistically significant difference was noted for sex (p = 0.33) or for race (p = 0.11). We believe this instrument to be of practical use in the assessment of enophthalmos or exophthalmos in patients whose facial deformity, trauma, surgery, or disease precludes the use of a rim-based exophthalmometry. PMID- 1520653 TI - Measurement of globe position in complex orbital fractures. II. Patient evaluation utilizing a modified exophthalmometer. AB - Globe position was assessed by both the Hertel exophthalmometer and the modified external auditory canal (EAC)-fixated device in 27 patients with complex orbital fractures (18 tripod and 9 Le Fort fractures). Although 94% of the patients with tripod fractures had relative exophthalmos on the fracture side or no difference between eyes by Hertel exophthalmometry, greater than 30% of the same patients showed relative enophthalmos when measured by the EAC-fixated device. In three of four patients undergoing surgical repair of the orbital floor, modified exophthalmometry showed exophthalmos of greater than or equal to 2 mm postoperatively on the fractured side. The relatively low incidence of enophthalmos in tripod fractures indicates a need for selective orbital floor repair; the uniform exploration of the orbital floor should be discouraged. Multiple comminuted facial fractures (Le Fort II and III) showed a greater variability in globe position and a high frequency (90%) of enophthalmos, suggesting a need for early orbital repair in these patients. EAC-fixated exophthalmometry can provide meaningful information regarding globe position in orbitofacial fracture patients in which orbital rim-based methods are precluded. PMID- 1520654 TI - Worsening of blepharoptosis in downgaze. AB - We report a group of patients with involutional blepharoptosis most pronounced in downgaze. Retrospective analysis was performed on all patients who underwent involutional blepharoptosis repair in a 30-month period. Physical examination and visual field testing confirmed the increased blepharoptosis in downgaze. The average increase in visual field obstruction is 12.5 degrees and the drop in the upper eyelid relative to the visual axis is 1.9 mm. We conclude that the increased visual field obstruction in downgaze in this subset of patients is significant and deserves clinical evaluation. PMID- 1520655 TI - Acquired ptosis: dehiscences and disinsertions. Are they real or iatrogenic? AB - Acquired ptosis has previously been felt to be due to a dehiscence or disinsertion of the levator aponeurosis. In the early years of levator surgery, the aponeurosis was often exposed by using blunt dissection. We have found that with a change in surgical technique, which eliminates blunt dissection, the incidence of aponeurotic defects decreases dramatically. Dehiscence and disinsertion may therefore be caused by traumatic surgical dissection of an attenuated aponeurosis. PMID- 1520656 TI - Complete ptosis as a result of removal of epibulbar lipodermoid. AB - Partial ptosis following epibulbar epidermoid removal is a known complication. The mechanism is generally thought to be symblepharon following aggressive dissection, injury to the levator aponeurosis, or injury to the branch of the ocular motor nerve to the levator muscle. We now report a case of complete ptosis thought to be neurogenic in origin. The possible mechanism is discussed. PMID- 1520657 TI - Botulinum A toxin for (expressionistic) ptosis overcorrection after frontalis sling. AB - Botulinum A toxin was injected into the frontalis muscle in two patients with complete third nerve palsies to limit intermittent upper lid retraction after a frontalis sling procedure. This form of lid retraction is noted during periods of active facial movement with occipitofrontalis muscle contraction. Although upper lid position may be symmetric when the facial muscles are adynamic, the upper lid may retract during periods of active facial expression. This type of lid retraction was corrected using Botulinum A toxin injections into the frontalis muscles, without affecting the lid position when the facial muscles are adynamic. Both improvement in appearance and intermittent exposure were noted in both cases. Additionally, a blunting of the transverse forehead creases occurred over a defined area after this injection, representing a clinical example of a denervation field produced by a point injection of botulinum toxin. PMID- 1520658 TI - Blastomycosis of the eyelid and conjunctiva. AB - A 37-year-old man with a recurrent papillomatous lesion of the upper eyelid and four separate bulbar conjunctival ulcers was found to have North American blastomycosis. This represents the first reported case with conjunctival lesions that were not simply contiguous with eyelid involvement. This case underscores the importance of considering blastomycosis in the differential diagnosis of granulomatous conjunctivitis and when examining a lesion of the eyelid resembling a squamous cell carcinoma or atypical papilloma. PMID- 1520659 TI - Spontaneous orbital subperiosteal hematomas in patients with liver disease. AB - Spontaneous orbital subperiosteal hematomas are rare entities. They are often associated with systemic coagulopathies. We present two cases of spontaneous orbital subperiosteal hematomas in patients with systemic coagulopathies resulting from liver disease. One patient was diagnosed with hepatitis B and had spontaneous resolution of the hematoma. Another patient had alcoholic cirrhosis and required an orbitotomy for drainage of a hematoma for compressive optic neuropathy. With the rising incidence of hepatitis B and the prevalence of alcoholic liver disease, it is important to include liver disease in the systemic evaluation of patients with spontaneous orbital subperiosteal hematomas. PMID- 1520660 TI - A simple method for lacrimal intubation. PMID- 1520661 TI - DNA flow cytometry of sebaceous cell carcinomas of the ocular adnexa: introduction to the technique in the evaluation of periocular tumors. AB - DNA content abnormalities are well recognized in tumor cell biology and kinetics. We introduce the technique of DNA flow cytometry through the study of the sebaceous cell carcinomas of the ocular adnexa. By correlating the data to the standard histopathologic parameters of pagetoid changes, degree of anaplasia, and stromal inflammation, significant associations are revealed. All aneuploid tumors demonstrate pagetoid spread, and more severe anaplasia and stromal inflammation. All diploid tumors are nonpagetoid and have lesser degrees of anaplasia and stromal inflammation. A complete review of the technique with a discussion of the implications and applicability to the study of ocular adnexal tumors is presented. PMID- 1520662 TI - Complications of surgery for orbital tumors. AB - Orbital tumors represent a small but significant portion of ophthalmologic surgery, and few reports of the associated complications are available. This retrospective review was undertaken to assess the overall complication rate of a large series of orbital tumors, as well as to determine possible risk factors that may guide surgeons in the future. There were 137 orbital tumors managed by a total of 14 surgeons at one hospital during a 7-year period. There was an overall 12.4% complication rate (17/137), affecting only 3 of 97 anterior orbitotomies (3%), but 14 of 40 lateral orbitotomies (35%). The location appeared to be the most significant factor, with the majority of complications associated with intraconal tumors. PMID- 1520663 TI - [Gather facts in order to have ideas]. PMID- 1520664 TI - [Clinico-statistical observations on malignant ocular tumors surgically resolved at the Cluj-Napoca Ophthalmological Clinic between 1970 and 1990]. AB - During the period mentioned above there ware hospitalized 54 patients having epibulbar tumours. The anatomopathological exam which was effectuated for 33 patients hes shown Bowen's disease for 14 cases, spinocellular carcinoma for 15 patients and basocellular for 3 patients. There were 4 cases for epibulbar precancerous. There was retinoblastoma for 19 cases; it had been practiced the enucleation of ocular globe for 17 patients and for two cases it had been practiced the exenteration of the eye socket. At the same period there were 91 uveal melanosis 6 of which having iridial localization, 10 cases of ciliary body [correction of cylar corpus], 75 cases of choroid. The hepatic scintigraphy was practiced for 56 patients and had shown for 8 cases hepatic metastasis. The histopathological exam of the melanomata of ciliary and choroidal corpus had shown type A fusiform cells for 22 cases, type B for 43 cases, epithelioid cells for 6 cases and mixed type cells for 13 cases. The hepatic metastasis were epithelioid cells for all the cases and, for 2 cases there were with mixed type cells, It is necessary an active discovering of intraocular and episcleral malign tumours, for increasing the chance of an earlier diagnosis during a stadium that would be able to be treated as conservator as possible be. PMID- 1520665 TI - [The eye manifestations in phosphorus-calcium metabolic disorders]. AB - The investigation of a number of 286 patients having disorders of binocular seeing shows a very frequent association of these to spasmophilia, especially for persons of feminine sex during their third or fourth decades of life. The medicamentous treatment of spasmophilia has ameliorated the disturbing binocular seeings, which had appeared again after stopping the treatment for a long time. The authors recommend the cover-test end the examination using Maddox's experiment for tracing rapidly out the binocular seeing disturbings. In order to stimulate the movements of the ocular globe in an reverse sense to the deviation formed by the oculomotor existed lack of poise, it had been used the prescription of classes with prisms assembled conversely to the classic rules, having the indication of wearing them for 3-4 hours a day. PMID- 1520666 TI - [Open-angle glaucoma yesterday and today]. AB - Glaucoma with open angle is now considered as an early optical neuropathy, that is determined by an uneasiness in flowing of the aqueous humour at the trabecular level. The ocular hypertension is the most frequent manifestation of the evolution of glaucoma, but it is not obligatory because there is a glaucoma with open angle that develop with low pressure. The automatically perimetry and the photography of the retinal arcuate fibers in aneritre light, may evidence incipient lesions before increasing of the ocular tension. Stereophotographies of the optic papillae make possible the calculus of the neuroretinal ring surface that replaces the old ratio cup/disk. The investigation of the microcirculation of the papillae, the determination of the papillar blood tide by pneumotonography and the velocimetry laser Doppler have brought new data for determining the incipient lesions of the optic disk. The large utilization of beta-blockings has changed the life of a glaucoma patient and the filtrant surgery has extended and diversified so being prolonged the visual function. PMID- 1520667 TI - [Obesity as a risk factor in diabetic retinopathy]. AB - The relations between the glucidic and lipidic metabolism fatness and diabetes are known for a long time. The fatness as a factor of risk for the diabetic retinopathy and consecutively for the appearance of the cecity have less been studied. There are studied the variations of lipids, cholesterol, the fatness (for 3 degrees by Broca) for a group of diabetic patients, type I or II, the age of the patients (between 18-80 years old) there are presented the retinal modifying: arterial, venous, microaneurysm, haemorrhages, the macular modifying. In comparison to the normoponderal diabetic patients, for these who are fat patients especially I or II degree, all the modifying are exaggerated. There was chosen the fatness from the lots of the factors of diabetes'risk, because I think it may be influenced. The treatments of retinopathy are few and less encourage. The doxium and the photocoagulation could eventually make the cecity to be late but they belong to the group of treatment, but it is not a prophylactic element for cecity. The real prophylaxis has to begin since the childhood with a normocaloric food diet. The prophylaxis of the diabetes is the true prophylaxis of the cecity. PMID- 1520668 TI - [Retinal venous obliteration and general pathology]. AB - The study of 148 retinal venous obliterations have shown 81 occlusions of central vein and 67 of I and II venous branch. A number of 90 was for the feminine gender (sex) and 59 for the masculine sex. The average age for the appearance of the venous occlusions was 62 years old, having extreme limits between 36-84 years old. Bilaterality has been for 3 cases. Concerning the associated medical affections, hypertension was for 67 patients, myocardiosclerosis have been mentioned for 67 patients, atherosclerosis for 21 patients, pulmonary scleroemphisis for 12 patients. Arterial hypertension with its aspersion that is arteriosclerosis are the main factors that have generated retinal circulation modifyings and have led to a degree of arterial insufficiency. Comparing the ophthalmological aspect to the pressure in the ophthalmic artery, most of the patients had a concordance of TACR and the retinal and choroidal angiosclerosis. The oscillometric examination to the inferior members has been effectuated for 21 patients and it has shown diminished values only for 3 cases. The forecast of the disease is still reserved. Following a group of 40 patients having OVR between 5 and 15 years old it has been established an average survival of 6.2 years. It is mentioned that 26% between these have dyed during the first six years. PMID- 1520669 TI - [The serology of toxoplasmosis in uveitis]. AB - Determinations for decelerating the antitoxoplasma anticorps that have been effectuated for 696 uveas proved positivity at 123 aerums (17.6%). The repartition of the positive serology concerning the clinic form of the uvea has proved 48 iridocyclitis, 26 serous central corioretinals, 23 in panuveitis, 13 in posterior uveitis, 11 muscular chorioretinitis, 2 in hyalitis. Taking into consideration only the equal or less than 1:160 titrures, these have been at 7 iridocyclitis, 4 serous central chorioretinitis, 4 panuveitis, 3 posterior uveitis and 3 atrophic central chorioretinitis. It is shown that the diagnosis of ocular toxoplasma must be effectuated just corroborating the clinic data with the positive serology. The antiparasitic treatment doesn't influence upon the low titrures of serous anticorps, which generally maintain at the same value all the life. PMID- 1520670 TI - [Heredity in myopia]. AB - The authors recall various theories that try to explain the appearance and the evolution of the short-sightedness. It is noticed the fact that none of these theories can include all the cases, but heredity proves a variable percentage. The examination of 200 cases of short-sightedness shows for 120 cases an hereditary factor. The transmission of it was dominant with variable penetration. Concerning the short-sightedness as a disease or malign one, the authors talk about a genetic condemnation of the sclera. PMID- 1520671 TI - [The marking of the anterior crystalloid in the extracapsular extraction of the crystalline lens by the intrasaccular (in the bag) technic]. AB - The authors try to mark the anterior crystalloid before sectioning it, using the chemical touch (solution three coloured acetic or sodium hydroxide) or by means of physical methods (electrocoagulation or diathermy for minimum electric power). In vivo the two last methods have given stable whitish points by the middle of which had been executed the sectioning of the crystalloid. The authors emphasize the advantages that are known by the technique of the extracapsular extraction of the crystalline in the bag and the simplifying of the manoeuvre for marking the anterior crystalloid. PMID- 1520672 TI - [Spontaneous luxation of the crystalline lens into the anterior chamber (a clinical case report)]. AB - A patient of 45 years old presents a sprained crystal in the anterior chamber, with secondary acute glaucoma at the left eye and surgically aphakia with ciliary staphyloma and optic atrophia for the right eye. VOR zero; VOL-PL; TOR-17,3 mm Hg; TOL-81, 9 mm Hg. After hypotension of the eye using a perfusion of mannitol and acetazolamide the ocular tension is normalized. It is practiced the extraction of the lens from the anterior chamber with a good post-surgically evolution. The disease may be joined to Marfan, Marchesani, syndrome homocystinuria or an early diagnosis of the zone without any manifest cause. PMID- 1520673 TI - [Toxoplasmic chorioretinitis and hydrocephalus]. AB - A child of 4 years old presents cicatricial toxoplasmic chorioretinitis, hydrocephaly and neurological disturbance. The titre of serous anticorps antitoxoplasma have been presented at 1/10. The child doesn't fix the objects, he presents nystagmus of fixation. Being in the presence of a case of congenital toxoplasmosis sequela stadium, it is not necessary a treatment. We insist upon a periodically control for the pregnant women and the treatment for those having positive serology. There are also necessary the prophylactic orders respecting the norms of hygiene and especially the use of milk and meat after an adequate thermic treatment of it. PMID- 1520674 TI - [Contact lenses, an alternative to classic eyeglasses?]. PMID- 1520676 TI - [How we speak, how we write]. PMID- 1520675 TI - [Sympathetic ophthalmia with an atypical onset]. PMID- 1520678 TI - [Correction with contact lenses. The components of correction with contract lenses]. AB - In order to understand the way contact lens adapts, we considered as a necessity the successive analysis of the components participating of the correction. Thus we have presented the role of the cornea and the evolution of the tear film under the contact lens. Afterwards contact lens of different types, corneo-scleral, hard or soft as well as the discontinuous, prolonged and permanent wear of lens have been presented. PMID- 1520677 TI - [The etiopathology of phacoantigenic uveitis and phacolytic glaucoma]. AB - The phacoantigenic uveitis is a self-immune affection at the lens proteins, which may be determined by a 3rd-type hypersensitivity, and some sterner forms by a 4th type hypersensitivity. In phacolytic glaucomas, the macrophagic reaction at degraded lens proteins obstructs the trabecular gaps, determining the raise of ocular tension with the appearance of secondary glaucomas. PMID- 1520679 TI - [The staging of malignant uveal melanoma]. AB - There have been investigated 30 malignant uveal melanomas hospitalized in the Ophthalmologic Clinic of Craiova during the last 15 years. The disease has developed more frequently among the female sex in a 3/2 proportion, the maximum age ranging between, 40 and 70 years old. As to the localization, 2 were at the level of the iris, 7 at the level of ciliary body and 21 at the choroid level. In anterior localizations tumour extirpation was possible in the 2 cases through iridectomy and in only one case through cyclectomy. Anatomicopathologically, most cases presented mixed-type cells where prevailed the type B fusiform cells and epithelioid cells with big quantitative variations from one zone to another. The tumours detected in an incipient stage benefited from laser photocoagulation or application of CO60 and I125 radioactive disks. In advanced stages enucleation was practised preceded by 2 treatments of radiotherapy for the devitalization of tumorous cells and prevention of metastases. PMID- 1520680 TI - [The genetic predisposition in open-angle glaucoma]. AB - The genealogic tree examination of a female patient with open angle glaucoma showed the presence of eight more cases of glaucoma in the same family. The transmission was autosomal predominant with a 75% penetration of the pathological gene. In the patient's family the affection appeared practically at the same age and evolved with the same specific feature. PMID- 1520681 TI - [The echographic diagnosis of intraocular tumors in children]. AB - The echographic exam done on 14 children with leukocoria (white pupil) confirmed in 7 cases the retinoblastoma diagnosis. The exam differentiates the solid tumours from the cystic ones and points out the tumours with non-typical clinical aspect. Results from here the great importance of echography effectuation, especially in non-typical forms with difficult clinical diagnosis. The association of the echographic examination, together with the classical methods of investigation, contributes to the establishing of a correct diagnosis of the size and exact extension of the tumour. PMID- 1520682 TI - [The importance of the pleoptophor in treating children with amblyopia]. AB - The author presents her own experience in pleoptic treatment, using the occlusion and the exercises at the amblyophor, on 161 children, during a 12 years period of time. The results of the therapy lead to cure in 38% of cases, to improvement in 46% of cases and fail in 16% of cases. The indications, the preparation, the practical development of the treatment at pleoptophor are discussed; the reasons of the failures are carefully analyzed. It is emphasized that the good results are due to the tracking down of children with strabismus in kindergartens, to the application of the amblyopic preventive optical treatment and to pleoptic treatment maintained for years with monthly checkups to prevent relapses. PMID- 1520683 TI - [Melanosis oculi and malignant choroid melanoma]. AB - The patient aged 75 years presents since her youth, in the left eye, ocular melanosis with abnormal pigmentation of the sclerotic, hyperpigmentation of the iris and abnormal pigmentation of the fundus oculi. Six months ago, she noticed that she is not able to see with this eye, and the fundus oculi examination emphasizes a malignant choroidal melanoma, with a fixed detachment of the retina. The authors show that the denomination Bourquin's benign ocular melanosis, under which the affection is known, is improper, as 10% of the cases of ocular melanosis degenerate into melanosarcomas. The term melanosis oculi is the most adequate one. PMID- 1520684 TI - [The practical aspects of the monocular wearing of a contact lens]. AB - The contact lens was prescribed to 64 cases, 38 of which having postsurgical monolateral aphakia. The lens extraction was made in 28 cases with traumatic cataract, 7 cases with complicated cataract and 3 cases with monolateral congenital cataract. The application of contact lens was made from two months to three years after the cataract operation; 6 patients wore before the surgical act usual glasses to correct the aphakia. After that the patients were called back monthly to controls; we used these opportunities to collect data about the advantages and disadvantages of contact lens wearing. PMID- 1520685 TI - [The artificial crystalline lens implant in diabetic patients]. AB - Are presented the results obtained by artificial lens pupillary implant (Fedorov) at 22 eyes, 18 patients between 48-81 years old, to which the development of cataracta was characterized by a great difference between the eyes. It have been obtained 63% very good visual acuity (5/10 and over) and 31% good (5/15-5/40). The authors Conclusion is the artificial lens implant may be done on diabetic patients if FO doesn't have great modifications. PMID- 1520686 TI - [A tuberculous etiology in Mikulicz's syndrome]. AB - A patient 20 years old presents bilateral hypertrophy of the lacrimal glands with discreet exophthalmos and conjunctival injection at the upper supero-external fornix level. The ocular affection appeared 6 weeks before as a painless tumefaction initially at the right eye and after that at the left eye also, with palpebral fold reduction. From childhood the patient has a ganglionary tuberculosis confirmed by the biopsy of a lateral cervical ganglion. Under the rim of the orbit on palpate the lacrimal gland as a depressible, painless mass, which is continued in the orbit. A lacrimal gland biopsy, effected at the left eye, shows the presence of dispersed nodules with round cells in the whole fragment of lacrimal gland, and epithelioid and giant cells in the center. The inflammatory phenomenon yield slowly with tuberculostatics generally and hydrocortisone in local instillations. PMID- 1520687 TI - [The ocular manifestations in craniopharyngioma]. AB - 11-years-old patient, for which the cranial radiograph shows modifications specific to craniopharyngioma, presents diminution of visual acuity at both eyes, psychic retardation and signs of insipidus diabetes. It is emphasized the unusual association between craniopharyngioma and exophthalmos, discordantly appeared on a background of global glandular insufficiency. PMID- 1520688 TI - [The invasion of neighboring structures in malignant choroid melanoma]. AB - It has been followed the microscopical evolution of the malignant melanoma of the choroid. After a stage of local growth, often with necrosis and intratumoral haemorrhages, it invades the neighbouring structures. The invasion of retina is produced at the apex level, making a breach in Bruch's membrane, the tumour becomes likewise a dumb-bell, a mushroom or a clepsydra. When the tumour is in contact with the retina, it produces a proliferation of pigmentary tumoral cells, glial cells and lymphoplasmocytary inflammatory reaction, which emphasize the sensorial retina detachment. The sclera invasion takes place especially in plaqued melanoma, through the points of minimal resistance which are the nervous routes, breaking up the scleral structures. The appearance of rudimentary vessels, with tumoural cells in lumen, constitutes a serous prognostic because of tumoural embolisms. PMID- 1520689 TI - [The adaptation to contact lenses]. AB - The indications of contact lens adaptation in optical purpose are widely large, starting, with refractive errors [correction of vices], unilateral and bilateral aphakia, myopia, anisometropia and astigmatism, together with the use of contact lens in esthetic purpose. We have been presented the adaptation techniques, the supervise, and maintenance of contact lens. PMID- 1520690 TI - Morphological characterization of exovesicles and endovesicles released from human erythrocytes following treatment with amphiphiles. AB - In order to morphologically characterize exo- and endovesicles released during treatment of erythrocytes with amphiphiles and to look for possible amphiphile specific effects on the vesiculation pattern, human erythrocytes were treated at 37 degrees C with amphiphiles at concentrations where they exhibit maximum protection against hypotonic haemolysis (cAHmax). Released exo-and endovesicles and treated cells were studied by means of transmission (TEM) and scanning (SEM) electron microscopy. All sphero-echinocytogenic amphiphiles induced a release of both spherical and tubular exovesicles. Dodecyl maltoside, a nonionic amphiphile with a bulky polar head, induced a release of predominantly tubular exovesicles, while all other sphero-echinocytogenic amphiphiles induced a release of predominantly spherical exovesicles. Some branched tubular exovesicles were released by a double-chained cationic amphiphile. Tail- and tongue-like structures were often seen on the exovesicles. Spherical exovesicles were frequently invaginated. Stomatocytogenic amphiphiles induced endovesiculation. In erythrocytes treated with most of the stomatocytogenic amphiphiles the endovesicles were clustered, but with some amphiphiles the endovesicles were randomly distributed. Large ringformed endovesicles (octaethyleneglycol alkyl ethers) and endovesicles in chains (octyl and decyl glucopyranoside) also occurred. The endovesicle membrane was often budding onto the lumen of the vesicle and in some cases this could ultimately lead to a vesicle inside the endovesicle. We conclude that amphiphiles do not only trigger vesiculation, but may also specifically affect the vesiculation processes. PMID- 1520691 TI - Induction of cystine transport in bovine pulmonary artery endothelial cells by sodium arsenite. AB - Sodium arsenite is one of a number of agents reported to induce a 30-34 kDa 'stress' protein in cells. Other agents which induce this stress protein, including diethyl maleate (DEM) and H2O2, have also been reported to be inducers of cystine transport in fibroblasts, macrophages, endothelial cells and other cell types. We have determined that micromolar levels of sodium arsenite increase cystine transport in bovine pulmonary artery endothelial cells (BPAEC), resulting in increases in intracellular glutathione (GSH). The increase in cystine transport appears to be due to stimulation of the synthesis of a protein analogous to the xc- transport system, a sodium-independent system specific for cystine and glutamate. We have determined that this stimulation is maximal between 8-16 h after addition of sodium arsenite and is inhibited by exogenous GSH. Others have reported that synthesis of the 30-34 kDa stress protein is maximal between 2-4 h and returns to baseline by 6-10 h. We conclude that cystine transport may be considered a 'secondary' stress response and is likely to be modulated by sulfhydryl-reactive agents. PMID- 1520692 TI - Stimulation-enhanced 3-O-methylglucose efflux from the frog sartorius: kinetics and properties of the system. AB - The characteristics of the process by which contraction enhances glucose transport in the frog sartorius were studied. Electrical stimulation increased the permeability of muscles to 3-O-methylglucose (3-O-MeGlc), a nonmetabolizable glucose analogue, increasing efflux as well as uptake. Enhanced efflux was due to an increase in Vmax of the efflux process. A lactacidosis had no effect on basal 3-O-MeGlc efflux, and replacement of media Na+ with Li+ did not affect stimulation-induced uptake. Also, basal and stimulated uptake was not affected by 1 microM 12-O-tetradecanoylphorbol-13-acetate (TPA), a protein kinase C activator. Lastly, N-carbobenzoxy-glycyl-L-phenylalaninamide, which inhibits insulin-enhanced, but not basal, glucose uptake in adipocytes, inhibited both basal and stimulated 3-O-MeGlc fluxes in the frog sartorius. From these findings, we conclude: (1) contraction and exercise enhance glucose transport in muscle by increasing the number of transporters in the plasma membrane, or their turnover, by an unknown process; and (2) basal glucose transport of muscle, unlike that of adipocytes, can not be distinguished from stimulated transport on the basis of its insensitivity to N-carbobenzoxyglycyl-L-phenylalaninamide. PMID- 1520693 TI - Identification of a broad-specificity nucleoside transporter with affinity for the sugar moiety in Giardia intestinalis trophozoites. AB - A broad-specificity nucleoside transporter has been identified in Giardia intestinalis trophozoites, using a rapid sampling assay to measure influx of [3H]deoxycytidine, [3H]adenosine and [3H]guanosine at 0 degrees C. The influx of each labelled nucleoside was inhibited strongly by all common, naturally occurring nucleosides but only poorly or not at all by nucleobases, indicating that the transporter recognizes structural features on the furanosyl moiety of ribo- and 2'-deoxyribonucleosides. Both 2'- and 5'-deoxyadenosine were potent inhibitors of influx (greater than 95% inhibition at 2 mM), whereas 3' deoxyadenosine was significantly less effective (approx. 70% inhibition), and 2',3'-dideoxycytidine and cytosine arabinoside were virtually inactive (0-20% inhibition). The data reveal that the 2'- and 5'-hydroxyl groups are not necessary for the recognition of nucleosides by this transporter. However, the 3' hydroxyl appears to be important. Michaelis-Menten constants (Km) were calculated for the influx at 0 degrees C of deoxycytidine (220 +/- 116 microM) and adenosine (45 +/- 24 microM), with respective Vmax values of 13 +/- 4 and 11 +/- 2 pmol min 1 (10(6) cells)-1. Only 12-26% of [3H]thymidine influx occurred through this transporter, the remainder entering the cells through a thymine/uracil-specific transporter described previously. Thymidine exhibited a Ki of 205 +/- 90 microM against [3H]deoxycytidine influx. PMID- 1520694 TI - A low-affinity nucleobase transporter in the protozoan parasite Giardia intestinalis. AB - A membrane transporter with general affinity for purine and pyrimidine bases has been identified in Giardia intestinalis trophozoites by measuring cellular influx of [3H]adenine, [3H]guanine and [3H]thymine at 0 degrees C. The base transporter is distinct from the thymine/uracil-specific (type 1) and broad-specificity (type 2) nucleoside transporters of G. intestinalis. Influx of each labelled base was retarded by unlabelled bases, with inhibition in the order: hypoxanthine greater than adenine greater than thymine greater than uracil. The IC50 values for these bases (measured for [3H]adenine influx) were 0.46 mM, 1.15 mM, 1.52 mM and 2.28 mM, respectively. Nucleosides did not inhibit base influx (less than or equal to 15% inhibition at 2 mM, a 400-fold molar excess, at which concentration [3H]nucleoside influx was inhibited by greater than 95%). The Michaelis-Menten constant (Km), calculated for adenine and thymine influx at 0 degrees C, was 1.44 +/- 0.08 mM and 1.61 +/- 0.37 mM, respectively, with corresponding Vmax of 383 +/ 16 and 498 +/- 112 pmol min-1 (10(6) cells)-1. The data demonstrate the existence of a low-affinity, facilitative base transporter with no detectable affinity for nucleosides. The inability of uridine or thymidine to significantly reduce the rate of thymine influx indicates that the previously described thymine/uracil-specific (type 1) thymidine transporter cannot transport thymine, despite its affinity for the base. PMID- 1520695 TI - The effects of 1,25-dihydroxyvitamin D-3 deficiency on Ca(2+)-transport and Ca(2+)-uptake into brush-border membrane vesicles from pig small intestine. AB - BBMV were prepared from duodenal segments of untreated, 1,25-(OH)2D3- or vitamin D-3-treated rachitic piglets and from non-rachitic controls by the Mg2+ precipitation method. The rachitic piglets were offspring from the 'Hannover Pig Strain' which suffer from pseudo vitamin D-deficiency rickets, type I (no renal 1 hydroxylase activity). Initial uptake of Ca2+ (up to 35 s) at low [Ca2+] (between 0.02-0.25 mmol/l) into isolated BBMV consisted of a saturable and non-saturable component. The apparent Vmax of the saturable component was significantly lower in rachitic piglets than in control piglets. In the presence of an inside negative potassium diffusion potential, the difference in uptake extended over at least 15 min. The apparent Km of Ca(2+)-uptake was not influenced by the rachitic condition. Treatment of rachitic piglets with sequential doses of 1,25-(OH)2D3 for three days (1 microgram/day) or with a single dose (2.5 mg) of vitamin D-3 elevated the saturable Ca(2+)-uptake component to values similar to those of control piglets. Addition of 1 mmol/l verapamil to the vesicular suspension inhibited Ca(2+)-uptake in BBMV of control piglets by 40-60% but was without effect on preparations from rachitic piglets. It was concluded from the study that 1,25-(OH)2D3 dependent Ca(2+)-uptake into BBMV constituted a saturable process which can be inhibited by a known Ca(2+)-channel blocking agent. It appears that 1,25-(OH)2D3 increases the number of verapamil sensitive Ca(2+) transport components in brush-border membranes. The vitamin D-dependent changes in vesicular Ca(2+)-uptake were paralleled by the expression of an active transmural Ca(2+)-transport across the mucosa. PMID- 1520696 TI - Opioid peptide interactions with lipid bilayer membranes. AB - The interaction of the delta-opioid receptor selective peptides, cyclic [D-Pen2, D-Pen5]-enkephalin [DPDPE] and its acyclic analog, DPDPE(SH)2, with neutral phospholipid bilayer membranes was examined by permeability and calorimetry measurements. The permeabilities were accomplished by entrapping either peptide inside of unilamellar liposomes (composed of a mixture of a molar ratio 65:25:10 phosphatidylcholine/phosphatidylethanolamine/cholesterol) then monitoring the peptide efflux through the bilayer. The initial permeability of DPDPE (first 12 h) averaged over four experiments was (0.91 +/- 0.47).10(-12) cm s-1. In contrast the average permeability of the acylic DPDPE(SH)2 was (4.26 +/- 0.23).10(-12) cm s-1. The effect of these peptides on the phase transition, Tm, of 1,2 dipalmitoylphosphatidylcholine (DPPC) bilayers was examined by high sensitivity differential scanning calorimetry. The Tm, the calorimetric enthalpy, and the van 't Hoff enthalpy of DPPC were not significantly altered by the presence of DPDPE, whereas the calorimetric data for DPPC with DPDPE(SH)2 showed a small, yet significant, increase (0.2 degrees C) in the Tm with a 30% decrease in the cooperative unit. Both the permeability and calorimetry data reveal a stronger peptide-membrane interaction in the case of the more flexible acyclic peptide. PMID- 1520697 TI - In vitro cytotoxicity of liposome-encapsulated doxorubicin: dependence on liposome composition and drug release. AB - We have investigated the in vitro cytotoxicity of free doxorubicin (DOX) and liposome-entrapped DOX (L-DOX) against a human ovarian carcinoma cell line (OV 1063) using a colorimetric assay. DOX was encapsulated in the inner water phase of liposomes by an ammonium sulfate-generated proton gradient. Liposomes varied in phospholipid composition but were of a similar size. It was found that the cytotoxic activity of L-DOX is substantially decreased when liposomes containing phospholipids of high phase-transition temperature (Tm) are used. The type of negatively charged headgroup did not have any significant influence on the cytotoxicity observed. Experiments using resin beads that bind free and protein bound DOX, but do not interact with L-DOX, indicated that the cytotoxic effect is mediated by the release of drug from the liposomes into the extracellular medium; no evidence was found for direct cellular uptake of liposome-encapsulated drug. The use of the ionophore nigericin to induce the release of DOX from high-Tm liposomes increased cytotoxicity to a level comparable to free DOX, suggesting that 'remote release' techniques may substantially improve the efficiency of liposome-mediated drug delivery and allow for the full exploitation of the favorable pharmacokinetic properties of specific high-Tm formulations. PMID- 1520698 TI - GM1b and GM1b-GalNAc: major gangliosides of murine-derived macrophage-like WEHI-3 cells. AB - WEHI-3 cells, derived from a BALB/c mouse, are a myelomonocytic leukemic cell line with macrophage-like properties. We have isolated, purified and characterized the monosialogangliosides from WEHI-3 cells by 1D-HPTLC, 2D-HPTLC, enzymatic degradation, HPTLC-immunostaining, gas-liquid chromatography and fast atom bombardment-mass spectrometry (FAB-MS). Quantitative 2D-HPTLC shows two monosialogangliosides are the major components, constituting 77% of the total, with a third monosialoganglioside being 3%. The two major components were identified as (NeuAc)GM1b and (NeuAc)GM1b-GalNAc and the minor component as (NeuAc)GM1b-GalNAc-Gal. The presence of GM1b in this myelomonocytic cell line is consistent with its presence in other murine immune cells and tissues. GM1b GalNAc and GM1b-GalNAc-Gal have been reported in T-lineage cells but not in resident or stimulated murine macrophages. Each of these monosialogangliosides belongs to the asialoGM1 synthetic pathway. Preliminary results indicate a disialo member of this pathway, GDlc, may also be present as a minor component. This ganglioside pathway, containing species which are not sialylated on the internal galactose, appears to be dominant in and may be characteristic of murine immune cells. PMID- 1520699 TI - Operation and energy dependence of the reducing-equivalent shuttles during lactate metabolism by isolated hepatocytes. AB - The participation and energy dependence of the malate-aspartate shuttle in transporting reducing equivalents generated from cytoplasmic lactate oxidation was studied in isolated hepatocytes of fasted rats. Both lactate removal and glucose synthesis were inhibited by butylmalonate, aminooxyacetate or cycloserine confirming the involvement of malate and aspartate in the transfer of reducing equivalents from the cytoplasm to mitochondria. In the presence of ammonium ions the inhibition of lactate utilization by butylmalonate was considerably reduced, yet the transfer of reducing equivalents into the mitochondria was unaffected, indicating a substantially lesser role for butylmalonate-sensitive malate transport in reducing-equivalent transfer when ammonium ions were present. Ammonium ions had no stimulatory effect on uptake of sorbitol, a substrate whose oxidation principally involves the alpha-glycerophosphate shuttle. The role of cellular energy status (reflected in the mitochondrial membrane electrical potential (delta psi) and redox state), in lactate oxidation and operation of the malate-aspartate shuttle, was studied using a graded concentration range of valinomycin (0-100 nM). Lactate oxidation was strongly inhibited when delta psi fell from 130 to 105 mV whereas O2 consumption and pyruvate removal were only minimally affected over the valinomycin range, suggesting that the oxidation of lactate to pyruvate is an energy-dependent step of lactate metabolism. Our results confirm that the operation of the malate-aspartate shuttle is energy dependent, driven by delta psi. In the presence of added ammonium ions the removal of lactate was much less impaired by valinomycin, suggesting an energy independent utilization of lactate under these conditions. The oxidizing effect of ammonium ions on the mitochondrial matrix apparently alleviates the need for energy input for the transfer of reducing equivalents between the cytoplasm and mitochondria. It is concluded that, in the presence of ammonium ions, the transport of lactate hydrogen to the mitochondria is accomplished by malate transfer that is not linked to the electrogenic transport of glutamate across the inner membrane, and, hence, is clearly distinct from the butylmalonate-sensitive, energy-dependent, malate-aspartate shuttle. PMID- 1520700 TI - Growth of human cultured cells exposed to a non-homogeneous static magnetic field generated by Sm-Co magnets. AB - A static magnetic field, with a strong spatial gradient, was established on the surface of cell culture dishes by use of a gilded iron needle set vertically above an Sm-Co magnet. The calculated magnetic flux density was more than 1.5 T at the center of the needle tip, and the products of the flux density and its gradient were about 200 and 60 T2/m at distances of 0.1 and 0.3 mm, respectively, from the center. The DNA content, DNA synthesis and labeling index of cultured cells located within 0.1 mm from the center of the needle, and the growth rate of cells located within 0.3 mm from the center, were measured. HeLa cells grew at a normal rate for 96 h in the magnetic field and showed no significant change in shape, detectable by scanning electron microscopy. The growth of HeLa cells was not influenced by exposure to the magnetic field. Similarly, exposure for 48 h to the magnetic field had no effect on growth of normal human gingival fibroblasts (Gin-1). The DNA content, assayed by microfluorometry of the nuclei of both types of cells stained by the Feulgen reaction, was not significantly different from that of controls. Moreover, exposure to the magnetic field had no effect on DNA synthesis or the labeling index of HeLa cells assayed by autoradiography of incorporated [3H]thymidine. It is concluded that a non-homogeneous magnetic field of the intensity and the gradient used in this study does not significantly influence the growth of HeLa cells or Gin-1 cells. PMID- 1520701 TI - Mechanism for endothelial cell injury induced by 15-hydroperoxyeicosatetraenoic acid, an arachidonate lipoxygenase product. AB - The mechanisms for endothelial cell injury induced by the lipid hydroperoxide 15 hydroperoxyeicosatetraenoic acid (15-HPETE), an arachidonate lipoxygenase product, were explored in cultured bovine endothelial cells. In serum-free medium, there was significant incorporation of [3H]-15-HPETE into the phospholipids of endothelial monolayers, and 15-HPETE induced severe endothelial cell injury, which was determined by the 51Cr-release assay. In contrast, in serum containing medium, there was little incorporation of [3H]-15-HPETE into the cells, and no cellular injury occurred. In the serum free condition, [3H]-15 HPETE was mainly incorporated into the phospholipids. The incorporated 15-HPETE produced lipid peroxidation, which was determined by the accumulation of malondialdehyde in the cells. The 15-HPETE-induced lipid peroxidation was suppressed by radical scavengers (MK-447, MCI-186), anti-oxidants (alpha tocopherol, butylated hydroxytoluene) and iron chelators (desferrioxamine,2,2' bipyridine). Furthermore, these agents also suppressed the 15-HPETE-induced cytotoxicity. These results indicate that 15-HPETE-induced endothelial cell injury depends on iron-mediated lipid peroxidation. PMID- 1520702 TI - Mechanisms for plasma-mediated activation of human blood cell aldehyde dehydrogenase. AB - Aldehyde dehydrogenase (ALDH; EC 1.2.1.3) activity assays were carried out on isolated human blood cells in phosphate-buffered saline (PBS) and in PBS mixed with human plasma. In assays with intact erythrocytes or sonicated leukocytes, the presence of 50% (v/v) or greater of plasma in the reaction mixtures produced a 2-fold increase in the rate of aldehyde oxidation. In corresponding assays with sonicated erythrocyte samples, the ALDH activity was enhanced on an average 1.5 fold, whereas a slight decrease was observed in assays with intact leukocytes. The ALDH inhibitor disulfiram almost completely abolished the enzyme activity both in the absence and presence of plasma. In assays with sonicated leukocytes, the activation effect could be antagonized by EDTA, indicating that it was caused largely by divalent cations. With sonicated erythrocytes, a significantly reduced ALDH activity was found only with the highest concentration of EDTA tested, and since a similar reduction was obtained also when plasma was omitted, the plasma mediated activation of erythrocyte ALDH was suggested to be due to a different mechanism. After separation of plasma by gel filtration, an active fraction was identified by GC-MS and 1H-NMR to contain pyruvic acid, lactic acid and glucose. When tested at physiological plasma concentrations, pyruvic acid caused an increase in erythrocyte ALDH activity similar to that obtained with plasma, while lactic acid and glucose did not. Pyruvic acid did not activate the leukocyte ALDH. Based on these results, it is indicated that the plasma-mediated activation of erythrocyte ALDH is due to pyruvic acid, which reoxidizes NADH via lactate dehydrogenase (EC 1.1.1.27) and, thereby, increases the rate of dissociation of NADH from the terminal enzyme-NADH complex, the rate-limiting step in the ALDH pathway. PMID- 1520703 TI - Guanine nucleotide regulatory protein levels and function in spontaneously hypertensive rat vascular smooth-muscle cells. AB - We compared G-protein levels and function in membranes from vascular smooth muscle cells (VSMC) derived from mesenteric arteries from SHR, WKY and Wistar rats. Basal adenylyl cyclase activity was significantly reduced in SHR membranes compared with Wistar, but was similar to WKY. Isoproterenol stimulation (10(-4) M) was significantly lower in SHR membranes compared to WKY, but was similar to that in Wistar, which was also significantly lower than WKY. Forskolin (10(-4) M) and NaF (10(-2) M), resulted in a higher stimulatory response in SHR membranes. Biphasic effects of GTP on isoproterenol-stimulated membranes demonstrated unaltered Gi function in SHR membranes. No significant differences were seen in the levels of Gs alpha (44- and 42-kDa forms), Gi2 alpha and the beta-subunit in immunoblotting studies of the membranes. Amounts of Gq alpha/G11 alpha and Gi3 alpha were also unchanged. In conclusion, there are differences in adenylyl cyclase responses in SHR VSMC membranes which are not a consequence of altered levels of G-proteins, but may reflect genetic differences rather than effects of hypertension. PMID- 1520704 TI - A human osteoblastic cell line, MG-63, produces two molecular types of macrophage colony-stimulating factor. AB - A human osteoblastic cell line, MG-63, mouse primary osteoblasts, and a mouse osteoblastic cell line, MC3T3-E1, were shown to produce macrophage-colony stimulating factor (M-CSF) by bone-marrow-cell colony assay, using a specific neutralizing antibody for M-CSF. Immunoblot analysis of M-CSF, produced by MG-63 cells, revealed the presence of a higher-molecular-weight species of M-CSF, in addition to the 85-kDa M-CSF. The higher-molecular-weight species had a high affinity to the DEAE-Sephacel column and was sensitive to chondroitinase ABC and AC. These physico-chemical profiles were wholly compatible with those of the proteoglycan form of M-CSF (PG-M-CSF), which was recently identified by our group in the conditioned medium of Chinese hamster ovary cells transfected with the 4.0 kb cDNA of the M-CSF gene. Conditioned medium of MG-63 cells was fractionated by DEAE-Sephacel column chromatography, and the M-CSF of each fraction was measured by both enzyme-linked immunosorbent assay and bone-marrow-cell colony assay. The fractions eluted by 0.3-0.6 M NaCl, which were shown to contain only PG-M-CSF on immunoblot analysis, also have macrophage-colony-stimulating activity. PMID- 1520705 TI - Angiotensin II and active phorbol esters induce proto-oncogene expression in isolated rat hepatocytes. AB - In isolated rat hepatocytes PMA, angiotensin II and to a lesser extent other hormones induce an early genetic response (increased expression of c-fos, c-mos, c-myc and beta-actin) without altering the expression of the glyceraldehyde 3 phosphate dehydrogenase gene. PMA, PDB and O-met-PMA, but not alpha-phorbol, stimulated c-fos expression. The effect of angiotensin II was inhibited by the AT1 antagonist, Losartan (DuP 753) (Ki approx. 25 nM), but not by the AT2 antagonist PD123177. Angiotensin II was much more effective than vasopressin or epinephrine in inducing proto-oncogene expression which suggests that angiotensin II receptors may exert actions in addition to those shared with the receptors for the other calcium-mobilizing hormones. The effect of PMA and angiotensin II on c fos expression took place rapidly, with half times of 7 and 12 min, respectively. Actinomycin D markedly diminished basal c-fos expression whereas cycloheximide had the opposite effect. Actinomycin D diminished the effect of PMA and angiotensin II but it did not block them. PMA and the calcium-mobilizing hormones increased c-fos expression above the level observed with cycloheximide alone. These data suggest that PMA and the calcium-mobilizing hormones increased both transcription of the c-fos gene and stabilization of the proto-oncogene mRNA. PMID- 1520707 TI - First National Congress of the Italian Association of Nuclear Medicine (AIMN). Milan, Italy, May 6-9, 1992. Abstracts. PMID- 1520706 TI - Gangliosides inhibit platelet-derived growth-factor-stimulated increases in intracellular calcium in Swiss 3T3 cells. AB - Individual Swiss 3T3 cells stimulated by platelet-derived growth factor delivered by means of a picopump device respond with a brisk, large, and sustained increase in intracellular calcium concentration ([Ca2+]i). Preincubation of cells with either GM1 or GT1b gangliosides inhibited the proportion of responding cells and caused a dose-related diminution in the magnitude of the increase in [Ca2+]i. This effect of ganglioside is probably part of the mechanism through which gangliosides exert their biological effects, including inhibition of platelet derived growth-factor-induced mitogenesis. PMID- 1520708 TI - [Seasonal changes in the human constant electrical field in various age groups]. AB - Seasonal changes of the constant electric field of healthy people of various age groups were studied. The constant electric field was shown to be characterized by a fine structure of distribution of electric potential differences (EPD) along the skin in relation to a referent point located on the neck in the intersection region of trapeziform and clavicular-nipple muscles. The constant electric field of the people of all ages undergoes seasonal changes involving displacement of all EPD values to the positive region during autumn-winter period as compared to the spring-summer one. It is suggested that such EPD change is conditioned by a change of the organism metabolic activity. The discovered differences in EPD displacement values of various age groups can serve as physiological characteristics of transitional processes in the growing organisms. PMID- 1520709 TI - [Origin and evolution of life and intellect from the point of view of information processing]. AB - Beginning of life and intellect on the Earth is determined by the fact that synthesis of semantic information about algorithms of chemical transformation for appointed classes of chemical compounds is not accompanied by the information synthesis, but is controlled by chance in genetic material. Genetic information as memorizing accidental choice always arises as a result of the environment interaction, when memorizing realization in the form of repeated reproduction occurs on the basis of processes radically different from those which created initial genetic chance. Such stepped synthesis of information has hierarchical character and it is described by entropy of different dimensions. Entropy is determined by conditional probabilities. Therefore as a form of life becomes complicated, the entropy is decreased within the limits of the given hierarchical step. The part of entropy depending on the number of elements of the system (cells, individuals, etc.) always increases in the memorizing process, i. e. life defines the maximum of entropy production (but not the minimum like in nature). This fact settles paradoxes of chance in Darwinism: as a result of entropy decrease within higher hierarchical step the simbiotic processes for more complex forms of life can arise with great probability. For instance, rapidity of evolution of human brain given by supplementary chance in the mechanism of fecundation under the conditions of biochemical pressure of androgenes both, on the brain development and on muscular force at the same time. Synthesis of information in the brain is determined by the same principles, but extremums of the thermo-dynamic potential (their analogues in logic) are based on an arbitrary system of axioms. As a whole life and intellect are not fluctuations pointed against entropy increases, but they arose according to spontaneous process of entropy development. PMID- 1520710 TI - [Activation of superoxide dismutase molecules under the effect of ultraviolet radiation]. AB - The effect of UV light (240-390 nm) with dose range 1.51-30.2 x 10(2) J/m2 on the functional properties of superoxide dismutase was investigated at various pH values. Photoactivation was shown to be maximum at pH values extreme for the display of superoxide dismutase activity. PMID- 1520711 TI - [Change in adaptability and kinetics of T-lymphocyte adaptation to hypotonia in pathological states of mammals]. AB - The kinetics of adaptation of the volume of T-lymphocytes and their membrane potential in a hypotonic medium is investigated. It is shown to have a quasiperiodic character. The shortest adaptation period T = 2 min characterizes the adaptation of T-lymphocytes test animals, the most complete adaptation of the volume and the membrane potential in hypotonic medium. Upon adaptation their values are only 6% higher than respective values in an isotonic medium. If an aseptic inflammatory process develops in a mammalian organism, the adaptation period increases to T = 2.5 min, while the volume and the membrane potential remains 28% higher than in an isotonic medium. In the course of development of induced cancerogenesis, 10 min after the cells have been placed in a hypotonic medium, their size is equal to that at the point of maximal swelling, while the membrane potential is 20% lower than that in an isotonic medium. The reason for the varying adaptability of T-lymphocytes is, in our opinion, that, as the inflammation develops, the concentration of corticosteroids increases, the concentration of intracellular K+ decreases, the concentration of macromolecules increases and the potential of the plasmatic membrane of the cell rises, thus leading to the slowing down of the process of adaptation and its decreased extent. The lack of regulation of the volume by T-lymphocytes of mammals in the organisms of which cancerogenesis develops, testifies to the fact that, in such a case, cells lose their adaptability to changing external conditions. Therefore, the disappearance of adaptability of T-lymphocytes on the third day of development of cancerogenesis represents an early test of the process. PMID- 1520712 TI - [Infrasound and biorhythms of the human brain]. AB - A relationship is established between the frequency of the human brain alpha rhythms and the frequency of infrasonic radiation emanating from overturned waves crests on the surface of seas and oceans. On this ground a recommendation is presented for maintaining the state of man's keeping awake. PMID- 1520713 TI - [Theory of sound attenuation in the blood and erythrocyte suspensions]. AB - Mechanisms of the ultrasound attenuation in blood and erythrocyte suspension in the long wave range are examined. It is shown that the theory proposed for dilute suspension of structured microobjects has a good coincidence with the known experimental data, both on erythrocyte suspensions and on blood. The contribution of viscous losses to attenuation are decreased with frequency and reach 44% in water suspensions of erythrocytes and 24% in the whole blood at 1 MHz. PMID- 1520714 TI - [Thermal properties of chromatin in vivo during interaction with cis[Pt(CuO)2(CuOH)2]]. AB - Thermal properties of chromatin in cell composition of BALB/c mice and whole chromatin at injection of cis-Pt(CuO)2(CuOH)2 to experimental animals were studied by high sensitive DSM assigning for investigating complex biological systems. It is established that injection of cis-Pt(CuO)2(CuOH)2 to leukemic mice in vivo changes the thermal characteristics of spleen cells, so that they look like the thermal properties of the healthy mice spleen cells. It was supposed that small doses of Pt(CuO)2(CuOH)2 in the case of leukemia show anticarcinogenic properties and the overdoses promote malignization; in the norm at any concentration of the injected salt cancerogenic properties are exhibited. PMID- 1520715 TI - [Conformation of a triple collagen spiral as a function of primary structure]. AB - It has been shown by the method of conformational analysis that conformation of the polypeptide chain of a collagen molecule varies from one type of sequence to another, but in all the sequences the only two types of conformations can be characterized by minimal conformational energy. The collagen molecule as a whole is a combination of the single-bond Rich and Crick model and new double-bonded structure. Rigorous comparison with "thick" conformations obtained by Scheraga and coworkers was undertaken using precise calculations with flexible proline. PMID- 1520716 TI - [Charge characteristics of two states of the actomyosin complex]. PMID- 1520717 TI - [An ellipsometric study of the antigen-antibody interaction in the interphase solid/solution area]. AB - Ellipsometric studies have proved that monoclonal immunoglobulin G(IgG) against gamma-interferon (gamma-INF) and immunoglobulin fraction (Ig-fraction) of rabbit blood serum against human serum albumin (HSA) are adsorbed according to the Langmuir model on the surfaces of mirror plates of covalently modified gamma-INF or HSA, respectively. The maximum surface concentrations (Tmax) and equilibrium adsorption constants (K) for IgG and Ig-fraction are equal to 2.57 pmol/cm2 and 2 x 10(7) M-1, 3.3 mg/m2 and 0.1 cm3/micrograms, respectively. The additional treatment of gamma-INF modified surfaces with Tween-20 leads to an increase of K IgG ut to 2.7 x 10(-7) M-1 while Tmax decreases up to 1.12 pmol/cm2 which is conditioned by the blocking of protein non-specific binding sites. The role of specific and non-specific interactions of IgG and Ig-fraction with covalently immobilized antigens was studied at antibody-antigen mixture adsorption. The necessity to apply this method to quantitative determination of gamma-IHF and HSA in solutions was proved. PMID- 1520718 TI - [Hydration of the left spiral of the poly-L-proline type. Study by the Monte Carlo method]. AB - The paper exhibits results of hydration shell Monte Carlo calculations in poly-L proline II and extended helix conformation and in alpha-helical and beta structural conformations for comparison. It was found that left-handed helix of poly-L-proline II type as well as epsilon-helix are characterized by very favorable hydration. Therefore this conformation has preference as compared to other standard conformations of the main polypeptide chain. This determined inevitability of cold denaturation of protein. PMID- 1520719 TI - [A new approach to the thermodynamic role of imino acids in collagen. Solution of a thermodynamic paradox]. AB - The dependence of denaturation transition thermodynamic parameters in various collagens from imino acid compositions has been analysed. Computational and experimental data suggest independence of the collagen molecule hydration on imino acid composition and sequence in the polypeptide chain. The continuous net of hydrogen bonds is interrupted, if imino acid residues occur in the sequence of amino acid residues, as follows from Monte Carlo computations, because the hydrogen of NH-group plays sufficient role in water shell formation for this conformation. As a consequence, entropy of denatured collagen-water system increases hand by hand with increasing imino acid content and therefore delta S increases. The increase of enthalpy of transition from imino acid content is determined by favorable Van der Waals interactions of pyrrolidine rings in native triple helical collagen structure. It was pointed out that proline role is determined by decreasing hydration in the single stranded polypeptide chain in Polyproline II conformation that leads to an increase of entropy of the polypeptide-water system. Thus, the collagen structure formation by imino acids is promoted in the water media due to single chain left-helical conformation being unfavorable for proline residues as well as due to the enthalpy nature of the triple helix stabilization. PMID- 1520720 TI - [Inhibition of psoralen sensitized photohemolysis by a marigold (Bidentis tripartita) extract]. AB - Hemolysis induced by psoralen and UV-A radiation (PUVA-hemolysis) was significantly inhibited by the addition of Bidentia tripartita extract. The rate of hemolysis was reduced both when the extract was present during irradiation, or added after PUVA-treatment. The inhibition effect was more pronounced when the extract was present during irradiation. PMID- 1520721 TI - [Dark and photosensitized hemolysis of erythrocytes in the presence of dithranol]. AB - Ditranol (1,8-dihydroxy-9-antrone) induced dark lysis of erythrocytes. After irradiation of the cells with UV-light (366 nm UV-A light) in the presence of ditranol (DUVA-effect) the hemolytic effect increases. It has been found that antioxidant butylated hydroxytoluene BHT in the concentration 10(-7) M did not affect the dark lysis, while with increased BHT concentration up to 10(-5) M the hemolytic effect of ditranol was intensified. The presence of BHT in the above concentration under DUVA-effect did not change the velocity of cell lysis. Sodium aside did not affect the dark hemolysis of ditranol, but it inhibited photosensitized hemolysis. PMID- 1520722 TI - [Reversibility of membrane damage during freezing by a paramagnetic doping method]. PMID- 1520723 TI - Modification of dry 1,2-dipalmitoylphosphatidylcholine phase behavior with synthetic membrane-bound stabilizing carbohydrates. AB - Carbohydrates, particularly disaccharides, have been shown to accumulate in organisms as protective solutes during periods of stress such as freezing and desiccation. Cholesterol and lipid derivatives containing the protective carbohydrates galactose or maltose, O-[11-(1-beta-D-galactosyloxy)-3,6,9 trioxaundecanyl]ol (TEC-GAL), O-[11-(1-beta-D-maltosyloxy)-3,6,9 trioxaundecanyl]ol (TEC-MAL), and 14-(galactosyloxy)-N,N-dimethyl-O (dipalmitoylphosphatidyl)- 6,9,12-trioxa-3- azoniatetradecanol (DP-GAL), have been synthesized to investigate the interaction of a protective carbohydrate moiety tethered to the 1,2-dipalmitoylphosphatidylcholine (DPPC) bilayer surface. Toward this goal, we have investigated the calorimetric and infrared spectroscopic behavior of mixtures of DPPC codried with these glycolipids. The synthetic glycolipids are shown to decrease significantly the main transition temperature (max Cp) of dry DPPC with a concomitant reduction in the cooperativity of the transition, as evidenced by a decrease in the enthalpy with increasing glycolipid. The decrease in transition temperature is shown to be related to chain melting monitored by the CH2 symmetric stretch frequency through the transition using FTIR. We also present evidence that the glycolipids interact with the interfacial region of DPPC, as shown by the decrease in the phosphate symmetric stretch intensity with increasing concentration of glycolipid. These observed effects are similar to the action of bulk protective sugars with DPPC; however, the concentration of glycolipid and the associated carbohydrate concentration needed to effect the observed changes are reduced compared to the quantity of bulk carbohydrate previously shown to give similar results with DPPC. PMID- 1520724 TI - Coupling of DTPA to proteins: a critical analysis of the cyclic dianhydride method in the case of insulin modification. AB - The reaction between the cyclic dianhydride of diethylenetriaminepentaacetic acid (DTPA), a bifunctional reagent, and proteins under various conditions was studied using porcine insulin as a model protein. The reaction was compared with that between citraconic anhydride, a monofunctional reagent, and insulin. Products were characterized chromatographically and electrophoretically before and after deesterification by hydroxylamine. A DTPA-conjugated product was further characterized by proteolytic fragmentation. The reaction with citraconic anhydride yielded the expected number of products exclusively acylated on amino groups. In contrast, the reaction with the cyclic dianhydride of DTPA under all conditions examined yielded a much higher number of products than expected. Among the products formed were O-acylated ones and products of intermolecular cross linking. It is concluded that the use of the cyclic dianhydride of DTPA does not allow the reliable preparation of proteins or other macromolecules conjugated with a high number of DTPA molecules in which each molecule of DTPA is linked to one amino group of the macromolecule through a single amide bond. PMID- 1520725 TI - Characterization of mercapturic acid and glutathionyl conjugates of benzo[a]pyrene-7,8-dione by two-dimensional NMR. AB - Non-K-region polycyclic aromatic hydrocarbon (PAH) o-quinones represent alternative metabolites of PAH trans-dihydro diol proximate carcinogens. These PAH o-quinones react readily with glutathione and N-acetyl-L-cysteine, and these adducts may be responsible for their detoxication. Reactions between benzo[a]pyrene-7,8-dione and either N-acetyl-L-cysteine or glutathione gave three predominant products which were purified by semipreparative reverse-phase high pressure liquid chromatography and characterized by homonuclear two-dimensional correlation spectroscopy (COSY). The first product corresponded to a Michael type, 1,4-addition product isolated at the level of quinone oxidation. The second product converted to the first and is a presumptive 1,4-addition product isolated at the level of hydroquinone oxidation. The third product was 7,8 dihydroxybenzo[a]pyrene (a hydroquinone) and was formed as a result of the reductive potential of the thiol. Additional proof for the catechol structure was obtained by its conversion to its diacetate and its identity with authentic 7,8 diacetoxybenzo[a]pyrene. The structures of these adducts and intermediates confirm that thiol addition involves formation of the ketol and rearrangement to give a catechol followed by oxidation to yield the quinone adduct. No evidence was obtained for the formation of either bisphenol or bisglutathionyl adducts. The COSY spectra provide the first complete structure of a benzo[a]pyrenyl peptide conjugate. PMID- 1520726 TI - Effect of different binding proteins on the detection limits and sensitivity of assays based on biotinylated adenosine deaminase. AB - The properties of binding proteins that control the nature and magnitude of inhibition of the enzyme-ligand conjugates in homogeneous enzyme-linked competitive binding assays were investigated. An assay for biotin that employed adenosine deaminase as the enzyme-label was used as a model system because of the availability of several biotin-specific binders with different characteristics. It was found that the association constant between the ligand and the binding protein, as well as the depth of the binding pocket, affect the response characteristics of the assay. In addition, the reported data suggest that steric hindrance effects also contribute toward the sensitivity and detection-limit capabilities of the assay. PMID- 1520727 TI - Molecular probes for muscarinic receptors: derivatives of the M1-antagonist telenzepine. AB - Functionalized congeners of the M1-selective muscarinic antagonist telenzepine (4,9-dihydro-3-methyl-4-[(4-methyl-1-piperazinyl)acetyl]-10H- thieno[3,4 b][1,5]benzodiazepin-10-one) were developed and found to bind to the receptor with affinities (Ki values) in approximately the nanomolar range. The derivatives contain a 10-aminodecyl group, which provides a nucleophilic functionality for further derivatization. The attachment of a spacer chain to the distal piperazinyl nitrogen was based on previous findings of enhanced affinity at muscarinic receptors in an analogous series of alkylamino derivatives of pirenzepine [J. Med. Chem. (1991) 34, 2133-2145]. The telenzepine derivatives contain prosthetic groups for radioiodination, protein cross-linking, photoaffinity labeling, and fluorescent labeling and biotin for avidin complexation. The affinity for muscarinic receptors in rat forebrain (mainly m1 subtype) was determined in competitive binding assays vs [3H]-N methylscopolamine. A (p-aminophenyl)-acetyl derivative for photoaffinity labeling had a Ki value of 0.29 nM at forebrain muscarinic receptors (16-fold higher affinity than telenzepine). A biotin conjugate displayed a Ki value of 0.60 nM at m2-receptors and a 5-fold selectivity versus forebrain. The high affinity of these derivatives makes them suitable for the characterization of muscarinic receptors in pharmacological and spectroscopic studies, for peptide mapping, and for histochemical studies. PMID- 1520728 TI - Carboranyl peptide-antibody conjugates for neutron-capture therapy: preparation, characterization, and in vivo evaluation. AB - Two model peptides rich in boron and prepared by Merrifield syntheses, dansyl.(nido-CB)2, (1) and dansyl.(nido-CB)10.Lys.Ac (2), where nido-CB represents the alpha-amino acid [nido-7-CH3-8-(CH2)3CH-(NH2)COOH-7,8-C2B9H10]-, were conjugated with the anti-CEA mAb T84.66 using peptide active ester reagents. The dansyl groups provided a means of fluorimetric analysis of mAb conjugates which was augmented by conventional amino acid analyses for nido-CB. The conjugate of 1 contained an average of 63 B atoms per mAb molecule. The mAb conjugate of 2 was chromatographically separated into a strongly fluorescent high molecular weight aggregated fraction (HMW) and a less intensely fluorescent monomeric fraction. Both fractions retained immunoreactivity. The HMW species contained an average of ca. 490 B atoms/mAb molecule, as determined by amino acid analysis. Biodistribution data were collected using nude mice bearing LS174T xenografts and 125I-labeled mAb conjugates. While the lightly B-loaded dipeptide conjugate gave biodistribution results which resembled those of native T84.66 mAb, the undecapeptide conjugate displayed greatly enhanced liver uptake and decreased tumor accretion. These results suggest that as the boron-containing burden on the supporting immunoprotein is greatly increased, as in the case of the T84.66-2 conjugate, loss of circulating conjugate to liver effectively competes with the desired tumor localization. Means which might be taken to circumvent this difficulty have been described elsewhere (ref 15). PMID- 1520729 TI - New chelating agent for attaching indium-111 to monoclonal antibodies: in vitro and in vivo evaluation. AB - 111In possesses excellent radiophysical properties suitable for use in immunoscintigraphy of cancerous tissues when attached to an antitumor antibody. However, 111In has a tendency to accumulate in normal tissues such as liver. Instability of the linkage between 111In and antibody may contribute to this problem. To avoid this, we developed a new bifunctional chelating agent, 1,3 bis[N-[N-(2-aminoethyl)-2-aminoethyl]-2-aminoacetamido]-2-(4- isothiocyanatobenzyl)propane-N,N,N',N'',N''',N'''',N''''',N'''''- octaacetic acid (LiLo), that forms a kinetically stable chelate with metal ions such as indium. Using LiLo, indium-111 was conjugated to a human monoclonal antibody, 16.88. Competitive binding analysis revealed that the 16.88-LiLo conjugate is as immunoreactive as the unconjugated native antibody. This conjugate was compared with 111In-16.88, where diethylenetriaminepentaacetic acid dianhydride (DTPAa) was used as the chelating agent. In vitro stability studies showed that 111In was more stably bound to 16.88-LiLo than to 16.88-DTPA. Biodistribution studies in athymic mice bearing colorectal tumor xenografts indicated less liver retention with 16.88-LiLo than with 16.88-DTPA. These results demonstrate that LiLo is superior to DTPAa for attachment of 111In to the monoclonal antibodies. PMID- 1520730 TI - New strategy in glycopolymer synthesis. Preparation of antigenic water-soluble poly(acrylamide-co-p-acrylamidophenyl beta-lactoside). AB - Stereospecific phase-transfer-catalyzed glycosidation of acetobromolactose 3 with p-nitrophenoxide gave the peracetylated 1,2-trans-beta-D-4-nitrophenyl lactoside 4. Functionalization of 4 into an N-acryloyl monomer was achieved by catalytic transfer hydrogenation of the nitro group, followed by N-acryloylation of the resulting amino group, on both O-acetyl-protected and unprotected disaccharides. Copolymerization of 4-acrylamidophenyl beta-lactoside (9) with acrylamide, initiated by ammonium persulfate, afforded a water-soluble carbohydrate copolymer (glycopolymer). The antigenicity of the new polymer was demonstrated by agar gel diffusion with Arachis hypogaea (peanut) and Ricinus communis (castor bean) lectins. Quantitative precipitation and enzyme linked lectin assays (ELLA) were also performed with peanut lectin. PMID- 1520732 TI - Characterization of an aromatic amino acid aminotransferase from Rhizobium leguminosarum biovar trifolii. AB - The most abundant aromatic amino acid aminotransferase of Rhizobium leguminosarum biovar trifolii was partially purified. The molecular mass of the enzyme was estimated to be 53 kDa by gel filtration. The enzyme transaminated aromatic amino acids and histidine. It used aromatic keto acids and alpha-ketoglutaric and oxalacetic acids as amino-group acceptors. The optimum temperature was 35 degrees C. Using phenylalanine and alpha-ketoglutaric acid as substrates the activation energy was 46.2 kJ.mol-1 and for the couple tryptophan:alpha-ketoglutaric acid it was 70.3 kJ.mol-1. The optimum pH was different for each substrate: 7.3 for phenylalanine, 7.9 for histidine and 8.7 for tryptophan. PMID- 1520731 TI - A novel galactose- and arabinose-specific lectin from the sponge Pellina semitubulosa: isolation, characterization and immunobiological properties. AB - A new lectin from the sponge Pellina semitubulosa is derived which was extracted and purified to homogeneity. The purified lectin is probably a hexamer of polypeptide chains (each M(r) 34,000) which are covalently linked via disulfide linkages; the isoelectric point is 6.1. The lectin displays the following specificities: D-galactose (50% inhibition of hemagglutination at 0.2 mM) = L arabinose (0.2 mM) greater than D-fucose (1.5 mM) greater than D-glucose (3.0 mM). It precipitates human erythrocytes (A1, A2, A1B, B, and O) with a titer between 2(8) and 2(11) and erythrocytes from sheep and rabbits with a titer between 2(5) and 2(10). The Pellina lectin displays a strong mitogenic effect on spleen lymphocytes from mice. Immunochemical analyses revealed that both murine T and B-lymphocytes display a capping of the lectin receptors on their cell surfaces after lectin treatment. Murine macrophages were found to endocytose the lectin. Pellina lectin at concentrations between 0.3 and 10.0 micrograms/ml potently enhances interleukin 1 (IL-1) release from mouse peritoneal macrophages and interleukin 2 (IL-2) production in mixed murine lymphocyte cultures. PMID- 1520733 TI - Modulation by dexamethasone of insulin binding and insulin receptor mRNA levels in U-937 human promonocytic cells. AB - Treatment with 5 x 10(-6) M dexamethasone stimulated insulin binding in human promonocytic U-937 cells. When curvilinear Scatchard plots were examined according to the one-site model, only changes in affinity, but not in receptor numbers, were observed. However, when the two-site model was applied, an increase in both the affinity and the number of the high affinity-low capacity sites was observed, with maximum values at 15 h. By contrast, the low affinity-high capacity sites did not undergo significant alterations. Northern blot assays revealed two insulin receptor-related mRNAs of approximately 11 and 7 kb in size. Dexamethasone increased the levels of these RNAs, following similar kinetics to those of high affinity receptor expression. This suggests that the 11 and 7 kb species carry information for high affinity insulin receptors, and that in U-937 cells the expression of this receptor subclass is primarily regulated at the mRNA level. PMID- 1520734 TI - Influence of dietary cholesterol on polyunsaturated fatty acid composition, fluidity and membrane-bound enzymes in liver microsomes of rats fed olive and fish oil. AB - Male rats were fed diets containing olive or marine fish oils (10% w/w) with or without added cholesterol (1% w/w). After six weeks of feeding, the major fatty acid composition, fluidity, fatty acid desaturating and cholesterol biosynthesis/esterification related enzymes of liver microsomes were determined. Both olive oil and marine fish oil diets, without added cholesterol, enriched content of oleic and docosahexaenoic acids, respectively, of rat liver microsomes. The results were consistent with reduction in delta 6 and delta 5 desaturation of n-6 essential fatty acids and higher fluidity in the marine origin oil group. Inclusion of cholesterol into diets resulted in decreased membrane arachidonic acid content, with concomitant increase in linoleic acid content. Cholesterol feeding also decreased delta 6 and delta 5 desaturase activities, as well as membrane fluidity. Furthermore, the activity of acyl CoA:cholesterol acyltransferase decreased, whereas the activity of hydroxymethylglutaryl-CoA reductase increased, in liver microsomes from both cholesterol-fat groups. PMID- 1520735 TI - Essential arginines in mercuric reductase isolated from Yersinia enterocolitica 138A14. AB - The mercuric reductase from Yersinia enterocolitica 138A14 was inactivated by the arginine modifying reagents 2,3-butanedione and phenylglyoxal. The inactivation by 2,3-butanedione exhibited second order kinetics with rate constant of 32 min-1 M-1. In the case of phenylglyoxal, biphasic kinetics were observed. The oxidized coenzyme (NADP+) prevented inactivation of the enzyme by the alpha-dicarbonyl reagents, whereas the reduced coenzyme (NADPH) enhanced the inactivation rate. The loss of enzyme activity was related to the incorporation of [2-14C] phenylglyoxal; when two arginines per subunit were modified the enzyme was completely inactivated. PMID- 1520736 TI - In vitro digestion of dystrophin by calcium-dependent proteases, calpains I and II. AB - Dystrophin is a cytoskeletal protein which is thought to play an important role in membrane physiology since its absence (due to gene deficiency) leads to the symptoms of Duchenne muscular dystrophy (DMD). Some disruption in the regulation of intracellular free Ca2+ levels could lead to DMD-like symptoms. In this study, calpains, which are very active calcium-dependent proteases, were examined for their capacity to hydrolyse dystrophin in vitro. The results show that calpains are able to split dystrophin and produce breakdown products of different sizes (the degree of cleavage being dependent on the incubation time with proteases). The time-course of protease degradation was examined by Western immunoblot using three polyclonal sera which were characterized as being specific to the central (residues 1173-1728) and two distal parts of the molecule ie specific to the N terminal (residues 43-760) or the C-terminal (residues 3357-3660) extremities of the dystrophin molecule. The cleavage patterns of dystrophin showed an accumulation of some major protease-resistant fragments of high relative molecular mass (250-370 kDa). These observations demonstrate that calpains digest dystrophin very rapidly when the calcium concentration is compatible with their activation. For instance, it is clear that calpains first give rise to large dystrophin products in which the C-terminal region is lacking. These observations suggest that dystrophin antibodies specific to the central domain of the molecule should be used to detect dystrophin for diagnostic purposes and before any conclusion as to the presence or absence of dystrophin can be deduced from results obtained using immunoanalyses of muscle biopsies. PMID- 1520737 TI - Evolutionary divergence plots of homologous proteins. AB - A simple and efficient method is described for analyzing quantitatively multiple protein sequence alignments and finding the most conserved blocks as well as the maxima of divergence within the set of aligned sequences. It consists of calculating the mean distance and the root-mean-square distance in each column of the multiple alignment, averaging the values in a window of defined length and plotting the results as a function of the position of the window. Due attention is paid to the presence of gaps in the columns. Several examples are provided, using the sequences of several cytochromes c, serine proteases, lysozymes and globins. Two distance matrices are compared, namely the matrix derived by Gribskov and Burgess from the Dayhoff matrix, and the Risler Structural Superposition Matrix. In each case, the divergence plots effectively point to the specific residues which are known to be essential for the catalytic activity of the proteins. In addition, the regions of maximum divergence are clearly delineated. Interestingly, they are generally observed in positions immediately flanking the most conserved blocks. The method should therefore be useful for delineating the peptide segments which will be good candidates for site-directed mutagenesis and for visualizing the evolutionary constraints along homologous polypeptide chains. PMID- 1520738 TI - Overproduction and purification of lysyl-tRNA synthetase encoded by the herC gene of E coli. AB - Lysyl-tRNA synthetases are synthesized from two distinct genes in E coli, lysS and lysU, but neither gene product has been purified distinctively by using overproducing systems. The lysS gene has been identified by a herC mutation which restores maintenance of the mutant ColE1 replicon. The herC gene product was overproduced by using a tac promoter fusion and purified to homogeneity. The purified HerC protein possesses a lysyl-tRNA synthetase activity as predicted by the sequence identity of herC to lysS. The procedure is useful for rapid mass scale purification of lysyl-tRNA synthetase. PMID- 1520739 TI - A comparison of case retrieval times: film versus picture archiving and communications systems. AB - One of the advantages that a picture archiving and communications system (PACS) is supposed to provide over a film-based operation is improved performance in retrieving images. Although it seems self-evident that this should be so, this experiment was intended to verify this and to provide some time comparisons for the two methods. The experiment consisted of randomly selecting ultrasound and computed tomography cases and determining how long it took to retrieve files at a PACS workstation or in person from the file room. To simulate actual retrieval volumes, a total of 40 cases from current to 6 months old, 20 cases from the past year, and 10 cases more than 1 year old was selected. Results indicate that PACS retrieval can indeed be faster than file room retrieval. However, the difference is less for recent cases than for older cases. For cases 6 or fewer months old, the workstation retrieval was approximately 2.5 minutes faster per case than the film file room. This time difference increased markedly when extended to the 1 year and older-than-1-year groups. This report details the results of this study and provides information about the reliability of the two archives. PMID- 1520740 TI - Design of a high-speed, high-resolution teleradiology network. AB - A teleradiology system acquires radiographic images from one location and transmits them to one or more distant sites where they are displayed and/or converted to hard-copy film recordings. The long-term goal of teleradiology research is to show that teleradiology systems can provide diagnostically equivalent results when compared with conventional radiographic film interpretation. If this hypothesis is proven, provision of the following radiology services will be improved: (1) providing for primary interpretation of radiological images for patients in underserved areas as well as in other medical facilities; (2) integration of radiological services for multihospital/clinic health care provider consortiums; (3) improving emergency service and intensive care unit coverage; (4) offering consulting-at-a-distance with subspecialty radiologists; and (5) providing radiologists in the community or in rural areas with immediate access to large academic centers for help in the interpretation of difficult and problematic cases. We are designing a high-speed, high-resolution teleradiology network that will communicate between our level 3 medical center and several outlying medical centers within the metropolitan area. Computed tomography (CT), magnetic resonance (MR), and screen-film examinations will be digitized to 2,000 x 2,000 or 4,000 x 4,000 pixels at the remote sites, transmitted to the central referral facility, and sent to a laser film printer, replicating the original film. This film may then be used for primary diagnosis, overreading/consultative purposes, or for emergency department preparation. Inherently digital modality data (eg, MR and CT) can be sent without digitization of the multiformat film if desired. PMID- 1520741 TI - Teleradiology via narrow-band integrated services digital network (N-ISDN) and Joint Photographic Experts Group (JPEG) image compression. AB - The importance of remote access to both radiological images and medical information has stimulated many demonstration projects that use a variety of telecommunications providers' offerings. Teleradiology, through modest cost channels, can achieve adequate response times using a combination of narrow-band integrated services digital network (N-ISDN) and data compression. A demonstration project, developed in collaboration with Southwestern Bell Technology Resources, Inc, uses the aggregate bandwidth of two B channels (achieving a rate of 120 kilobits per second) and a block-oriented discrete cosine transform compression/decompression implementation based on the Joint Photographic Experts Group Standard for Still Image Compression. System response measurements for an Inquiry and Display Station accessing the Mallinckrodt Institute of Radiology's Radiology Image and Information Management Testbed via the N-ISDN connection show response times to be within 20 seconds. Viewing applications have been shown at sites within St Louis and at Radiological Society of North America, 1990, in Chicago. PMID- 1520742 TI - Quality monitoring of soft-copy displays for medical radiography. AB - As presentation of medical radiographic images on soft-copy displays (cathode ray tubes) becomes increasingly prevalent in electronic radiography, methods of quality assurance must be developed to ensure that radiologists can effectively transfer film-based reading skills. Luminance measurements provide the basis for evaluating the state of soft-copy displays. An integrated approach has been implemented at Mallinckrodt Institute of Radiology (MIR, Washington University, St Louis, MO) that facilitates measurement of geographically distributed soft copy displays with centralized data logging, performance tracking, and calibration. MIR's central radiology image manager exercises the display station that drives the monitor, harvests the measurement data, stores the results, and submits the resulting data for additional processing. The luminance measurements are collected by a small, portable, photometric instrument designed at MIR that includes a serial port that is accessed via local area terminal service supported by the radiology image manager. The design details of the photometric instrument and example luminance characteristics of several soft-copy displays used at MIR are presented in this report. PMID- 1520743 TI - Compressed radiological images and workstation viewing. AB - The viewing of radiological images on workstations has peculiarities that must be taken into account in the design of a compression technique. The images may be manipulated on a workstation to change the contrast, to change the center of the brightness levels that are viewed, and even to invert the images. Because of the possible consequences of losing information in a medical application, bit preserving compression is used for the images used for diagnosis. However, for archiving, the images may be compressed to 10% of their original size. A compression technique based on the discrete cosine transform takes the viewing factors into account by compressing the changes in the local brightness levels. The compression technique is a variation of the Consultive Committee on International Telephony and Telegraphy Joint Photograph Experts Group compression that suppresses the blocking of the discrete cosine transform except in areas of very high contrast. PMID- 1520744 TI - Portable image-manipulation software: what is the extra development cost? AB - A hospital-wide picture archiving and communication system (PACS) project is currently under development at the University Hospital of Geneva. The visualization and manipulation of images provided by different imaging modalities constitutes one of the most challenging component of a PACS. It was necessary to provide this visualization software on a number of types of workstations because of the varying requirements imposed by the range of clinical uses it must serve. The user interface must be the same, independent of the underlying workstation. In addition to a standard set of image-manipulation and processing tools, there is a need for more specific clinical tools that can be easily adapted to specific medical requirements. To achieve this goal, it was elected to develop a modular and portable software called OSIRIS. This software is available on two different operating systems (the UNIX standard X-11/OSF-Motif based workstations and the Macintosh family) and can be easily ported to other systems. The extra effort required to design such software in a modular and portable way was worthwhile because it resulted in a platform that can be easily expanded and adapted to a variety of specific clinical applications. Its portability allows users to benefit from the rapidly evolving workstation technology and to adapt the performance to suit their needs. PMID- 1520745 TI - Orientation correction for chest images. AB - This report presents an automatic procedure that determines the orientation of computed radiography (CR) chest images and rotates them to a standard position to be viewed by radiologists. As an input, CR images of a normalized size of 1,000 x 1,000 or 2,000 x 2,000 pixels are used. The analysis is performed in three steps. First, the orientation of the spine within the image is determined. Then, a function searches for upper extremities and the subdiaphragm. Finally, the lungs are extracted and their areas are compared. This indicates whether the image needs to be y-axis flipped. These three steps set the value of three parameters on the basis of which the final rotation angle is determined. The procedure has been implemented in the clinics at UCLA. The rate of correctly rotated images is 95.4%. PMID- 1520746 TI - Recognition of chest radiograph orientation for picture archiving and communications systems display using neural networks. AB - A neural network classification scheme was developed that enables a picture archiving and communications system workstation to determine the correct orientation of posteroanterior or anteroposterior chest images. This technique permits thoracic images to be displayed conventionally when called up on the workstation, and therefore reduces the need for reorientation of the image by the observer. Feature data were extracted from 1,000 digitized chest radiographs and used to train a two-layer neural network designed to classify the image into one of the eight possible orientations for a posteroanterior chest image. Once trained, the neural network identified the correct image orientation in 888 of 1,000 images that had not previously been seen by the neural network. Of the 112 images that were incorrectly classified, 106 were mirror images of the correct orientation, whereas only 6 actually had the caudal-cranial axis aligned incorrectly. The causes for misalignment are discussed. PMID- 1520747 TI - Potential of digital flashing tomosynthesis for angiocardiographic evaluation. AB - A system for digital flashing tomosynthesis (DFTS) consists of four electrocardiogram-gated and simultaneously flashed x-ray tubes, a 14" image intensifier, a unit for digital subtraction angiography (DSA), a personal computer-hosted transputer network for three-dimensional (3D) reconstruction as well as for quantitative coronary angiography and ventriculography, a display unit and an individual digital archive. DFTS-tomoangiograms may be presented in single slice mode or as multiple slices of arbitrary thickness, using rotating and stereographic presentation of 3D images. DFTS represents a configuration for standardized digital angiocardiography with digital archiving and assures optimal reproducibility and safety. This angiographic configuration is feasible for both ambulatory angiography to allow high volume cardiovascular angiographic screening and for the quantitative assessment of natural progression or potential regression of coronary artery disease resulting from interventional or pharmacological therapy. PMID- 1520748 TI - [Dietetic and pharmacologic treatment of hypercholesterolemia. Study of 32 patients over 14 months]. AB - The aim of the study was to evaluate the effectiveness of dietetic-behavioural and pharmacological treatment on 32 patients with high level hypercholesterolemia (LDL-c greater than 160 mg/dl) over 14 months. Clinical and laboratory tests were performed at time 0 (enrollment), at time 1 (after 2 months dietetic-behavioural treatment only), at time 2 and time 3 (after 6 and 12 months respectively of combined dietetic-behavioural and pharmacological treatment). The dietetic behavioural treatment consist of reduced intake of saturated fatty acids, cholesterol and rapidly absorbed glycid; increased intake of omega-3 fatty acids and fiber; reduced overall calorie intake. The patients were also advised to take light daily exercise. The pharmacological treatment (sinivastatin 20 mg/die) was given to patients whose total cholesterol levels were over 250 mg/dl after 60 days of dietetic-behavioural only treatment and then continued for the whole study. The result showed an average reduction of 20% (p less than 0.01) in LDL-c in all patients after dietetic-behavioural only treatment and a further 20% (p less than 0.01) reduction after 12 months of combined treatment. There was therefore confirmation of the validity of dietetic-behavioural and pharmacological treatment during our study. PMID- 1520749 TI - [Fecal chymotrypsin and steatorrhea in chronic pancreatitis]. AB - The aim of the present study was to evaluate in 56 patients (48 M, 8 F) with chronic pancreatitis: a) the diagnostic validity of fecal chymotrypsin (FCT) assay, performed both on random samples and from previously homogenized samples collected over 3 days; b) the correlation between chymotrypsin and fecal fat excretion. CTF was measured using Kaspar's colorimetric method and fecal fats using the Van de Kamer method. Mean values of chymotrypsin measured on random samples were very similar to those measured on previously homogenized feces, 17.9 +/- 16.7 U/g vs 17.1 +/- 15.3 U/g respectively. There was a highly significant correlation between these values (r = 0.77 p less than 0.0003) and a highly significant inverse correlation between fecal fat and chymotrypsin excretion, both when the latter was measured on random and on previously homogenized samples (p less than 0.0001). FCT assay was fairly good sensitive (54%) for the whole group of patients with chronic pancreatitis, but very good (91%) for the group of patients with steatorrhea. The results show that the fecal chymotrypsin assay on random fecal samples is as valid as that carried out on homogenized feces and that there is a good correlation between fecal chymotrypsin values and steatorrhea of pancreatic origin. PMID- 1520750 TI - [Polyps of the proximal colon: rightward shift, malignancy potential and symptomatology]. AB - To evaluate the neoplastic risk of polyps of the right hemicolon we assigned 202 polyps larger than 4 mm, consecutively resected, to two groups according to their location, proximal or distal to the splenic flexure. We compared sex and age of the patients and the following characteristics of the polyps: size 10 mm and over, adenomatous and villous component, presence of severe dysplasia and absence of a stalk. We found that polyps in the proximal colon were less frequently dysplastic and smaller; on the other side fewer of them had a stalk. A significant rightward shift was observed in the male patients over 65 years old. Apparently right hemicolon polyps are less prone to overt clinical bleeding. PMID- 1520751 TI - [Epidemiology of lesions caused by non-steroidal anti-inflammatory agents]. PMID- 1520752 TI - Hepatotoxicity of hydroxy-methyl-glutaryl-coenzyme A reductase inhibitors. AB - The first clinical studies on hydroxy-methyl-glutaryl-coenzyme A (HMG-CoA) reductase inhibitors reported a low incidence of liver toxicity. The personal observation of a case of simvastatin-induced acute cholestatic hepatitis prompted us to evaluate the true incidence of hepatic side effects of these drugs in a large Italian population. One hundred patients taking simvastatin and ninety patients treated with pravastatin were followed-up six months with periodical evaluation of serum lipid levels and liver function test. In 5% of simvastatin treated patients and 4.5% of pravastatin-treated patients significant liver toxicity was observed, which required drug discontinuation. The mechanism of liver damage was direct, idiosyncratic, but immunological features of drug toxicity could be hypothesized in one patient. PMID- 1520753 TI - [Assessment of gallbladder motility in patients with alcoholic hepatic cirrhosis after a fatty meal. A real-time ultrasonography study]. AB - Gallbladder emptying after fatty meal administration was investigated by real time ultrasonography in 10 patients with alcoholic cirrhosis of the liver, and 10 normal controls. Gallbladder volume was measured using the sum of cylinders method before and 5', 15', 20', 30', 60', 90', and 120' after fatty meal administration. Patients with liver cirrhosis presented the gallbladder volume significantly increased after 15' and 20', and significantly reduced after 60' and 90' in respect to controls. A significant difference was found between the groups in the two curves, patients showing a retarded contraction of gallbladder. The mechanism for sluggish gallbladder emptying in liver cirrhosis is unknown, however impaired emptying with bile stasis provides a potential pathophysiology basis for the high frequency of cholelithiasis in this disease. PMID- 1520754 TI - [Metastasis to the penis from carcinoma of the rectum. A clinical case]. AB - Penile metastases are extremely uncommon, with less than 300 reported cases. The primary sites of the responsible carcinoma have been bladder, rectum, prostate, kidney, testis, lung, nasopharynx and melanoma in that order. We report a case confirming the same data: no therapy has been shown to be helpful, the prognosis is very poor, with an average survival of less than one year. On the other hand we pointed out the importance of CT scan as a diagnostic tool for assessing the spread of neoplasm. PMID- 1520755 TI - [Comparison between a diet with mainly vegetal protein content and a diet with mainly animal protein content in hepatic cirrhosis]. AB - Eight cirrhotic patients were studied in a randomized crossover single blind study in order to compare the effects of two isocaloric, and with equal amount of protein diets on nitrogen balance and on the portal systemic index. One diet was 2:3 vegetable protein to total protein content (diet V) and the other 2:3 animal protein to total protein content (diet A). Each diet was changed every three weeks. Five patients followed the VAV scheme and three the AVA scheme. The mean values of the porto systemic index were almost the same with the two diets while the value of the nitrogen balance was less negative with the diet A than with the diet V, showing an increasing trend, more marked with the diet A, at every consecutive time of observation. The variance analysis was not significant for any of the two diets. Diet V was well tolerated. PMID- 1520756 TI - Infectious complications of indwelling vascular catheters. PMID- 1520757 TI - Toxoplasmic encephalitis in AIDS. AB - Involvement of the central nervous system (CNS) is common in patients with advanced disease due to human immunodeficiency virus (HIV). Symptoms range from lethargy and apathy to coma, incoordination and ataxia to hemiparesis, loss of memory to severe dementia, and focal to major motor seizures. Involvement may be closely associated with HIV infection per se, as in the AIDS dementia complex, but is frequently caused by opportunistic pathogens such as Toxoplasma gondii and Cryptococcus neoformans or malignancies such as primary lymphoma of the CNS. The clinical presentations of attendant and direct CNS involvement are remarkably non specific and overlapping, yet a correct diagnosis is critical to successful intervention. Toxoplasmic encephalitis is one of the most common and most treatable causes of AIDS-associated pathology of the CNS. A great deal has been learned in the last 10 years about its unique presentation in the HIV-infected patient with advanced disease. Drs. Benjamin J. Luft of the State University of New York at Stony Brook and Jack S. Remington of the Stanford University School of Medicine and Palo Alto Medical Foundation's Research Institute have studied T. gondii for many years and are two of the leading experts in the field. This commentary comprises an update of their initial review (J Infect Dis 1988;157:1 6) and a presentation of the current approaches to diagnosing and managing toxoplasmic encephalitis in HIV-infected patients. PMID- 1520758 TI - Parasiticidal effect of chemotherapy in alveolar hydatid disease: review of experience with mebendazole and albendazole in Alaskan Eskimos. AB - Evidence that the larval stage of Echinococcus multilocularis in humans is killed by chemotherapy is presented in a review of our 17-year experience with treatment of alveolar hydatid disease in Alaska. The efficacy of chemotherapy was assessed with use of an in vivo assay of parasite viability by means of inoculation of voles, immunohistochemical tests, and histopathologic findings. Of 14 tests performed for nine patients, 12 in vivo assays (86%) were negative after chemotherapy, while only two (17%) of 12 vole tests for seven untreated patients were negative. Regression of arrest of growth of metastatic and primary hepatic lesions, together with their partial-to-complete calcification and prolonged survival times has been observed among patients treated with the benzimidazole compounds. For six who received appropriate chemotherapy, treatment has been discontinued for an average of 4.6 years (range, 3-7 years) without an increase lesion size or other evidence of reactivation. PMID- 1520759 TI - Two cases of endocarditis due to Lactobacillus species: antimicrobial susceptibility, review, and discussion of therapy. AB - Endocarditis caused by lactobacilli may lead to death or to relapse of infection, despite antimicrobial treatment. We report two cases of lactobacillus endocarditis in individuals with native bicuspid aortic valves who survived without relapse and review the 39 other cases reported in the literature. In only 15 previously reported cases have patients been cured with medical therapy alone. One of our patients, who was infected with Lactobacillus acidophilus, was cured by medical therapy alone, and our other patient, who was infected with Lactobacillus casei subspecies rhamnosus, required surgical replacement of his aortic valve. L. acidophilus was tolerant and L. casei subspecies rhamnosus was resistant to many antibiotics tested. Combinations of penicillin or daptomycin and gentamicin were synergistic by time-kill assay. Synergistic therapy with a penicillin and an aminoglycoside was effective clinically and appears to provide optimal medical treatment on the basis of microbiological data. PMID- 1520760 TI - Measures of capillary permeability in acute falciparum malaria: relation to severity of infection and treatment. AB - Capillary permeability was investigated in 32 Thai patients aged 14-49 years who had acute falciparum malaria with use of three distinct techniques: quantitation of the urinary albumin/creatinine ratio (ACR), estimation of the transcapillary escape rate of radiolabeled albumin (TER), and retinal photography/fluorescein angiography. Fourteen patients had uncomplicated infections and 18 were severe cases. The severely ill patients had significantly higher ACRs (median, 4.8 mg/mmol; 95% confidence limits, 2.4-19.9 mg/mmol) and TERs (median, 8.3%/h; 95% confidence limits, 6.2-13.2%/h) than the uncomplicated cases (ACR: median, 2.1 mg/mmol; 95% confidence limits, 6.2-13.2%/h) than the uncomplicated cases (ACR: median, 2.1 mg/mmol; 95% confidence limits, 1.0-8.8 mg/mmol; TER: median, 5.9%/h; 95% confidence limits, 3.8-10.6%/h; P = .014 and .042). Both variables were significantly associated with biochemical indices of disease severity including total serum bilirubin levels (rs greater than or equal to 0.398, P less than .025 in each case), but there were no significant differences between ACRs and TERs among comatose and noncomatose patients with severe infections (P greater than or equal to .08). Retinopathy (hemorrhages, cotton-wool spots, capillary nonperfusion, and/or extravasation of fluorescein) was found in eight severely ill patients and in two uncomplicated cases. Fluorescein leakage was evident in six patients. Although fluorescein leakage had the strongest parametric correlation with the presence of coma relative to both ACR and TER in the full patient series (r = 0.58, P less than .01), multiple linear regression analysis indicated that concentrations of plasma lactate (t = 2.998, P = .006) and serum creatinine (t = 2.200, P = .036) were the factors responsible for this association. These data do not support a role for tissue edema in the pathogenesis of cerebral malaria but reveal an association between markers of disease severity and a generalized increase in systemic capillary permeability. PMID- 1520761 TI - Toxoplasmosis in bone marrow-transplant recipients: report of seven cases and review. AB - We report seven cases of cerebral or disseminated toxoplasmosis that occurred following bone marrow transplantation (BMT) and review the other 24 cases described in the literature. For all the cases, toxoplasmosis occurred within 6 months of BMT, with the highest incidence in the second and third months. Twenty four of 26 recipients tested serologically before BMT were positive for Toxoplasma gondii, a finding that supports the view that such cases result from reactivation of latent infection. At the onset of clinical symptoms, IgG antibody titers were unchanged or decreased in 23 of 25 documented cases, and IgM antibodies were detected in two cases. Antemortem diagnosis was made in 16 cases and was based on the response to specific therapy in six cases and/or the demonstration of the parasite in body fluids or tissues in 10 cases. Autopsy was performed in 19 cases and revealed that infection was not restricted to the brain but either involved lung or heart tissue or was disseminated in 14 cases. PMID- 1520762 TI - Vibrio vulnificus infection in Taiwan: report of 28 cases and review of clinical manifestations and treatment. AB - From May 1985 through July 1990, 28 episodes of Vibrio vulnificus infection in 27 patients were encountered in five major hospitals in Taiwan. The ages of patients ranged from 19 to 76 years; the ratio of male to female patients was 2:1. Eighteen episodes manifested as bacteremia and eight as wound infections alone. One patient each developed gastroenteritis and pneumonia after nearly drowning. Twenty-three patients exhibited skin manifestations. Twenty patients had underlying diseases. All patients were treated with antibiotics, and 14 also underwent some form of surgical treatment (incision and drainage, fasciotomy, debridement, or amputation). Thirteen of the 28 episodes were preceded by precipitating factors; most were due to ingestion of seafood or exposure of abraded skin to salt water. Ten of the 18 septicemic patients died--most within 48 hours of hospitalization. One patient without bacteremia who had a wound infection died. Results of in vitro susceptibility studies suggested that ampicillin or a third-generation cephalosporin would be effective. Susceptibility to aminoglycosides was observed for greater than 90% of isolates. We recommend combined therapy with a third-generation cephalosporin or ampicillin and an aminoglycoside along with appropriate surgical therapy for the treatment of V. vulnificus infection. PMID- 1520763 TI - Clusters of invasive group A streptococcal infections in family, hospital, and nursing home settings. AB - The spread of group A streptococcal infection to close contacts of infected persons is well recognized. With the resurgence of invasive group A streptococcal infections, there is an increased potential for clusters of patients with invasive disease. We reviewed data collected since December 1988 at the Centers for Disease Control (Atlanta) to identify clusters of infection in which one or more patients had invasive disease. Twelve family clusters were identified. Infection in index cases included the toxic shock-like syndrome and septicemia. Infection in family contacts included invasive infections, pharyngitis, or asymptomatic carriage. Most invasive disease occurred in adults, while the majority of noninvasive infections were in children. Five nosocomial clusters with spread of infection from patients to hospital personnel were documented. All index patients had the toxic shock-like syndrome; secondary infections included the toxic shock-like syndrome, pneumonia, bullous cellulitis, lymphangitis, and pharyngitis. Clusters of invasive infections also were identified in five nursing homes. Pneumonia, cutaneous infections, and the toxic shock-like syndrome occurred most commonly. Clustering by nursing home unit occurred in three outbreaks. In hospitals and nursing homes, improved infection control will likely decrease secondary spread; in families, spread of disease may be prevented by identifying and treating those harboring the organism or by chemoprophylaxis. Studies that characterize the rate of secondary infection are needed before definitive recommendations can be made. PMID- 1520764 TI - Chronic arthritis after rubella vaccination. AB - In August 1991 the Institute of Medicine released a report entitled "Adverse Effects of Pertussis and Rubella Vaccines" that examined, among other relations, the relation between immunization with the RA 27/3 rubella vaccine strain and chronic arthritis. The committee spent 20 months reviewing a wide range of information sources including case series and individual case reports published in peer-reviewed journals and reported by vaccine manufacturers; unpublished case reports from physicians, parents, and other concerned persons; epidemiological studies; and laboratory studies. There were no animal studies available. The committee found that the evidence is consistent with a causal relation between the RA 27/3 rubella vaccine strain and chronic arthritis in adult women, although the evidence is limited in scope. Proving that rubella vaccination can cause chronic arthritis will require a better understanding of pathogenetic mechanisms and additional well-designed studies. We briefly describe the committee's evaluative methods and present the evidence underlying its conclusion. PMID- 1520765 TI - Superantigens, T cells, and microbes. AB - It is well recognized that toxins of Staphylococcus aureus and Streptococcus pyogenes are responsible for a wide range of clinical conditions, although their precise mode of action remains unclear. Recently, there has been a resurgence of interest in these toxins, now grouped with superantigens, because they cause profound alterations in the immune system homeostasis. Superantigens are molecules, including endogenous retroviral gene products and microbial toxins, that share a unique set of characteristics. They bind with high affinity to major histocompatibility complex class II at regions distinct from the conventional antigen binding groove and cause prolific activation or anergy of T cells with certain T cell receptor variable-region gene families. Whilst most of the superantigens described to date are products of bacteria or viruses, the presence of superantigens in parasites and their role in disease pathogenesis remain to be defined. It is probable that associations are present between superantigen induced proliferation or anergy of peripheral blood T cells and clinical manifestations of human infectious diseases. The identification of these may pave the way toward a better understanding of disease pathogenesis and the possible development of newer immunotherapeutic regimes. This review summarizes the current thinking on microbial superantigens, their association with human T cells, and speculations about their significance. PMID- 1520766 TI - Endocarditis due to Neisseria mucosa: two case reports and review. AB - Two cases of endocarditis caused by Neisseria mucosa are reported, and the literature on N. mucosa endocarditis is reviewed. N. mucosa is a rare but serious cause of endocarditis that is associated with a high rate of embolic complications and high mortality and is not always highly sensitive to benzylpenicillin. Most patients with N. mucosa endocarditis have been treated with combined therapy with penicillin and an aminoglycoside, although the optimal regimen has not been defined. PMID- 1520767 TI - Pleural infection caused by Capnocytophaga canimorsus, formerly CDC group DF-2. AB - An 80-year-old man with Waldenstrom's macroglobulinemia developed pneumonia and empyema due to Capnocytophaga canimorsus (formerly CDC group DF-2). No growth was detected in blood cultures, but the organism was identified from cultures of pleural fluid. The infection responded well to antibiotics and drainage via a chest tube. To our knowledge, this is the first report of a clinical isolate of C. canimorsus from a pulmonary source. The absence of concurrent bacteremia raises the possibility that the lower respiratory tract can be the site of primary infection with this organism. PMID- 1520768 TI - Severe pneumococcal sepsis and meningitis in human immunodeficiency virus infected adults with sickle cell disease. AB - Pneumococcal infection is frequent in children with sickle-cell disease (SCD) but is less common in adults. Infection due to human immunodeficiency virus (HIV) is also a risk factor for pneumococcal infection. The purpose of this study was to determine the clinical course of HIV infection in adults with SCD. During a 6 year period, 283 adults suffering from SCD were screened for HIV type 1 and HIV type 2 infections. The clinical course of HIV infections in these patients was retrospectively analyzed at the term of the study. HIV type 1 infection was detected in eight patients. The mean follow-up period after diagnosis of HIV infection was 4.6 years. None of the patients had AIDS. Five episodes of severe pneumococcal infection were observed in four of these eight patients (septic shock in two patients and three episodes of meningitis in two patients); two patients died of meningitis. Only one severe pneumococcal infection (meningitis) was observed in the 275 non-HIV-infected patients with SCD (P = .000001). Our results show that pneumococcal infection appears to occur frequently and is often serious in HIV-infected adults with SCD. PMID- 1520769 TI - Epidemiology and clinical significance of nontuberculous mycobacteria in patients negative for human immunodeficiency virus in Switzerland. AB - Over the last decades, the rate of isolation of tubercle bacilli has declined in the developed countries, while the incidence of infection with nontuberculous mycobacteria (NTM) has increased. In a retrospective study, we analyzed all cases of patients negative for human immunodeficiency virus (HIV) and from whom NTM were isolated in the Zurich area of Switzerland from 1983 to 1988. During the 6 year study period, 513 patients infected with NTM were identified, 34 of whom had clinically significant disease. The presentation of mycobacteriosis was found to be lung disease in 23 cases, soft-tissue disease in 10 cases, and disseminated disease in one case. The highest attack rate of pulmonary mycobacteriosis was 0.49% and was found in the group of patients 41-50 years old. During the 6-year period, the incidence of tuberculosis declined from 16.2 to 13.2 per 100,000 population, while the incidence of mycobacteriosis increased from 0.4 to 0.9 per 100,000 population. Clinically nonsignificant NTM isolates were found more frequently in patients with chronic lung diseases (P less than .01) and especially in patients with a history of tuberculosis (P less than .001). PMID- 1520770 TI - Implications of viral resistance to amantadine in control of influenza A. AB - Antiviral agents are valuable adjuncts to vaccine in the control of type A influenza. Amantadine has been available for many years for prophylaxis and therapy, but there have been concerns about side effects, particularly in the elderly. Thus, the anticipated licensure of rimantadine, an antiviral with the same efficacy as amantadine but with fewer side effects, has been viewed as a major advance. Rimantadine has thus far remained unlicensed, and attention has become focused on antiviral resistance to these drugs, an issue previously recognized but not considered important in decisions concerning drug use. The major implications of antiviral resistance relate to questions of whether there are differences in pathogenicity and transmissibility of resistant influenza type A viruses in comparison with sensitive ones. Resistant viruses have not been found to be more virulent than sensitive ones. The extent to which they may be transmitted or perpetuated has not been established. In light of this situation, it is suggested that drug use not be sharply restricted and that recommendations be periodically reviewed as more definitive data become available. As with any infectious disease, attempts should be made to limit exposure of uninfected individuals to those infected with the influenza A virus, regardless of whether they are receiving an antiviral drug. PMID- 1520771 TI - Antiendotoxin monoclonal antibodies for gram-negative sepsis. PMID- 1520772 TI - Oxygen tensions and mycobacterial infections. PMID- 1520773 TI - Spotless boutonneuse fever. PMID- 1520774 TI - Use of cefotaxime for treatment of Acinetobacter infections. PMID- 1520775 TI - Group B streptococcal prosthetic joint infection following sigmoidoscopy. PMID- 1520776 TI - Primary pneumococcal peritonitis and bacteremia in an immunocompetent woman. PMID- 1520777 TI - Recovery of Bordetella bronchiseptica from patients with AIDS. PMID- 1520778 TI - Fatal measles pneumonia in an immunocompetent patient--case report. PMID- 1520779 TI - Recovery from myasthenia gravis of a patient infected with human immunodeficiency virus. PMID- 1520780 TI - Group A streptococcal meningitis. PMID- 1520781 TI - Cluster of Bell's palsy cases found among hospital employees. PMID- 1520782 TI - Helicobacter pylori: its role in disease. PMID- 1520783 TI - Bacterial brain abscesses: factors influencing mortality and sequelae. AB - Thirty-nine cases of brain abscess diagnosed since the advent of the computed tomographic (CT) scan were analyzed for factors influencing the outcome. The mortality rate was 13%, and severe sequelae were present in 22% of the survivors. The mean delay between occurrence of the first symptoms and hospitalization was significantly shorter for the 12 patients with poor outcome (death or severe sequelae) than for the 25 who recovered (fully or with moderate sequelae). Moreover, severely impaired mental status and neurological impairment at admission were associated with a poor outcome in terms of both mortality and sequelae. In all cases with fatal outcome or severe sequelae, the diagnosis was made and treatment was initiated within 24 hours of admission. There was no apparent correlation between the outcome and the presence or type of predisposing factors, the radiological, biological, or microbiological findings, or the treatment modalities. Thus, with the advent of the CT scan and the possibility of early diagnosis and treatment, the prognosis of brain abscess appears to be mainly determined by the rapidity of progression of the disease before hospitalization and the patient's mental status on admission. PMID- 1520784 TI - Septic arthritis and bacteremia due to Mycoplasma resistant to antimicrobial therapy in a patient with systemic lupus erythematosus. AB - We report a case of septic arthritis caused by Mycoplasma hominis in a patient with systemic lupus erythematosus. The infection started as monarthritis but spread to at least four joints despite apparently suitable therapy with various antimicrobial agents, including doxycycline, clindamycin, and ciprofloxacin; subsequent bacteremia was documented. Control was ultimately achieved with use of the experimental fluoroquinolone temafloxacin in combination with doxycycline administration, arthroscopic drainage of a persistently infected joint, several intravenous infusions of immunoglobulins (which led to increases in levels of antibodies specific to M. hominis), and discontinuation of corticosteroid therapy. Antimicrobial susceptibility testing of various mycoplasmal isolates showed the presence of the tetM gene, disparity between susceptibility to tetracycline and doxycycline, and increasing resistance to most antimicrobial agents used (including to fluoroquinolones before clinical use), although the patient ultimately had a favorable clinical response to treatment with combined modalities. PMID- 1520785 TI - Imported malaria in pregnancy: report of four cases and review of management. AB - Malaria is a common infection worldwide. Increased travel by pregnant women makes it likely that physicians in the United States will see cases of malaria in this population. We observed four cases of malaria during pregnancy over an 8-month period at a general hospital in the United States. These cases illustrate the association between pregnancy and severe malaria in the mother and congenital infection in the newborn. We also noted delays in diagnosis because malaria was mistaken for other common illnesses. Therapy was complicated by concerns about the safety of antimalarial agents for the fetus and newborn as well as drug resistance. While chloroquine is safe for use in pregnancy, drug resistance is now common, especially when the etiologic organism is Plasmodium falciparum. There are concerns about the safety of administering other antimalarial agents during pregnancy (e.g., mefloquine). Concerns about the safety and availability of these agents limit options for prophylaxis. PMID- 1520786 TI - Candidemia in a tertiary care hospital: epidemiology, risk factors, and predictors of mortality. AB - Demographic information, risk factors, therapy, and outcome for all patients who had candidemia at Barnes Hospital, St. Louis, between 1 September 1988 and 1 September 1989 were retrospectively reviewed. One hundred six candidemic patients were identified, representing 0.5% of all medical and surgical discharges and 0.33% of total patient discharges. These percentages represent a 20-fold increase in the incidence of candidemia at our hospital in comparison with that during 1976-1979. Candida albicans was the most frequently isolated species (63%), followed by Candida tropicalis (17%), Candida glabrata (13%), Candida parapsilosis (6.5%), and Candida krusei (0.9%). Overall mortality was 57%, and 14 (23%) of 60 deaths occurred within 48 hours of the detection of candidemia. Mortality was associated with higher APACHE II scores (25 for nonsurvivors vs. 16 for survivors; P = .0001), the presence of a rapidly fatal underlying illness (P = .0009), and sustained positivity of blood cultures (P = .02). In cases of sustained candidemia, the isolation of non-albicans Candida species also correlated with increased mortality (8 of 8 vs. 10 of 21; P = .005). Thirty candidemic patients (28%) did not receive any antifungal therapy, and 19 (63%) of these untreated patients died. Eleven untreated patients (37%) survived without sequelae. There has been a marked increase in the incidence of candidemia in our institution that is associated with a high overall mortality. Candidemia lasting less than 24 hours was associated with a lower mortality than was that of longer duration. Severity of illness and duration of candidemia should be used as stratifying factors in prospective studies to determine optimum therapy. PMID- 1520787 TI - Should all patients with candidemia be treated with antifungal agents? PMID- 1520788 TI - Plasma and whole blood exchange in meningococcal sepsis. AB - The present study describes the effect of plasma exchange or whole blood exchange (PEBE) on the survival rate among patients with fulminant meningococcal sepsis and on the level of circulating endotoxin. Since 1989 all patients with meningococcal disease and hypotension who were admitted to our intensive care unit were treated with PEBE. Results for our patients were compared with those for a historical control group conventionally treated between 1984 and 1989 (n = 10; mortality rate, 60%); the expected mortality rate, which was based on the Niklasson prognostic score and was calculated for seven patients in this control group, was 73%. A total of 15 patients were treated with PEBE, three (20%) of whom died, whereas the prognostic score (calculated for 14 patients) for this group was 62%. In two of the fatal cases, PEBE was started after a delay of greater than or equal to 40 hours. In the remaining 13 patients, PEBE was started within 5-30 hours after the first hospital admission. The mortality rate among this group was 8% (one of 13 patients); this rate was significantly different from that among the control group (P = .025). For seven patients treated with PEBE, plasma endotoxin concentrations were sequentially measured. The overall half-life (+/- SEM) of endotoxin was 181 +/- 18 minutes. This is approximately the same as reported values for patients who were not treated with PEBE. It is concluded that early initiation of PEBE may improve the rate of survival among patients with meningococcal infection and hypotension but that the mechanism of the beneficial effect is most likely not based on the elimination of endotoxin. PMID- 1520789 TI - Blood exchange and plasmapheresis in sepsis and septic shock. PMID- 1520790 TI - Fatal septicemia due to Mycoplasma arginini: a new human zoonosis. AB - A 64-year-old slaughterhouse worker with advanced non-Hodgkin's lymphoma developed septicemia and pneumonia. Mycoplasma arginini, a wall-free prokaryote found in a variety of domestic animal hosts, was repeatedly isolated from blood and bronchial washings from the patient. Immunosuppression, in part caused by hypogammaglobulinemia, probably played a key role in predisposing the patient to a fatal infection. This case suggests that animal mycoplasmas should be considered in the list of infectious agents acquired by immunosuppressed hosts. PMID- 1520791 TI - Rocky Mountain "spotless" and "almost spotless" fever: a wolf in sheep's clothing. AB - In 10 (10.8%) of 93 laboratory-confirmed or probable cases of Rocky Mountain spotted fever seen at Duke University Medical Center from 1969 to 1991, illness without rash or fleeting or atypical skin eruptions were noted. Data from these 10 cases and 33 similar previously reported cases of Rocky Mountain "spotless" or "almost spotless" fever support the premise that human Rickettsia rickettsii infection has a broader spectrum than that indicated by its classic description. Sixty-one percent of patients with Rocky Mountain spotless or almost spotless fever have been men. Two-thirds have been black. Although in some cases the absence of rash may be due to the prompt institution of therapy with chloramphenicol or tetracycline, in others long delays in recognition of the disease and treatment occurred, resulting in the deaths of 53% of patients. On the basis of outcome in the cases reviewed, empirical administration of chloramphenicol or a tetracycline to selected patients is justifiable (including those patients with severe organ dysfunction), even if they have no rash, a transient rash, or a rash of unusual distribution. Indeed, without such therapy, patients with spotless or almost spotless fever may die. Recognizing such atypical cases is analogous to seeing a wolf in sheep's clothing--intuition, experience, knowledge, and a high index of suspicion are required. PMID- 1520792 TI - Epidemiology of Aeromonas infections in California. AB - In May 1988, California became the first state to make aeromonas infection a reportable condition, thereby permitting the first population-based study of the epidemiology of infection caused by Aeromonas organisms. Case investigations were carried out on 219 of the 280 patients whose infections were reported during the first year of notification. The overall incidence rate for Aeromonas isolation was 10.6 cases per 1 million population. The gastrointestinal tract was the most commonly reported site from which Aeromonas was isolated (81%), with wounds being the next most common source (9%). Five (2%) of the 219 patients died; all five had serious underlying medical conditions apart from aeromonas infection. No common-source enteric outbreaks were reported. The high rate of gastrointestinal symptoms and isolation of organisms from medically vulnerable patients and the fact that other bacterial enteric pathogens were rarely isolated from symptomatic patients support evidence from previous studies that Aeromonas is an enteric pathogen. The evidence from these case reports in California suggests that aeromonas infections are not an important public health problem and are largely nonpreventable. Thus, public health surveillance is not necessary and mandatory reporting has been discontinued. PMID- 1520793 TI - Infections due to Nocardia transvalensis: clinical spectrum and antimicrobial therapy. AB - Nocardia transvalensis, a rare Nocardia species, has previously been recognized as a cause of actinomycotic mycetoma. In a retrospective review of N. transvalensis isolates referred to the Centers for Disease Control (Atlanta) during the period January 1981 through January 1990, we identified 15 patient isolates. Four N. transvalensis isolates originated from one Australian reference laboratory; one patient's isolate that was identified by the Australian laboratory but that was not received at the Centers for Disease Control was also included in our study. A review of the cases of these 16 patients found that N. transvalensis caused infection in 10 patients and colonization in two patients. Six (75%) of eight patients with primary pulmonary or disseminated N. transvalensis infections had an underlying immunologic disorder or were receiving immunosuppressive therapy; three patients with disseminated infection died. All nine infected patients for whom specific antimicrobial therapy was prescribed received trimethoprim-sulfamethoxazole. Results of in vitro antimicrobial susceptibility tests of 11 N. transvalensis isolates revealed increased antimicrobial resistance to amikacin and other drugs when compared with that of other Nocardia species. Severely immunocompromised patients are predisposed to N. transvalensis pneumonia or disseminated infection, and the lung may be the portal of entry. PMID- 1520794 TI - Diloxanide furoate for treating asymptomatic Entamoeba histolytica cyst passers: 14 years' experience in the United States. AB - Diloxanide furoate is used for treating asymptomatic or mildly symptomatic persons who are passing cysts of Entamoeba histolytica. The Centers for Disease Control (Atlanta) released this drug for 4,371 treatment courses from 1977 through 1990. Of the 2,815 report forms (64%) returned, 656 adverse effects were reported for 390 treatment courses (14%); they included flatulence (260), diarrhea or cramping (100), nausea (93), headache (17), disorientation or dizziness (9), and diplopia (4). During 1984-1990 uniform collection of data allowed more detailed analysis of toxicity and efficacy; fewer adverse effects were reported for persons aged 20 months to 10 years than for persons aged greater than 10 years (6 of 206 [3%] vs. 89 of 763 [12%], relative risk = 0.27, 95% confidence interval = 0.12 less than relative risk less than 0.61). Parasitological cures were achieved during 497 (86%) of the 575 treatment courses (52%) administered to asymptomatic persons who were passing cysts, who had received a full 10-day treatment course, and for whom results of a follow-up stool examination (greater than or equal to 14 days post-treatment) were available. Diloxanide furoate is safe and effective for treating asymptomatic persons who are passing E. histolytica cysts and may be particularly well tolerated in children. PMID- 1520795 TI - Disseminated Nocardia brasiliensis infection with septic arthritis. AB - An unusual case of disseminated Nocardia brasiliensis infection is presented. The patient, who had been receiving chronic dexamethasone therapy for 4 years, had pneumonia and septic arthritis of the left knee due to N. brasiliensis. To our knowledge, this is the first report from the United States of a synovial joint infection with this organism. Disseminated disease due to N. brasiliensis is infrequently reported; it is most often seen in the immunocompromised patient and is often unresponsive to therapy. PMID- 1520796 TI - Evaluation of eight serological tests in the diagnosis of human echinococcosis and follow-up. AB - The ELISA with use of IgG, IgA, and IgE, latex agglutination, indirect hemagglutination (IHA), total IgE, the radioallergosorbent test (RAST), and immunoelectrophoresis (IEP) were carried out to determine the preoperative diagnosis of infection due to Echinococcus granulosus in 131 patients. Eighty nine patients received follow-up care for 42 +/- 22 months (mean +/- SD); 72 were treated surgically and 17 with mebendazole only. We analyzed 5 +/- 2 serum samples per patient and analyzed each serum sample using the eight tests. IgG ELISA was the most sensitive (up to 94%) and specific (up to 99%) test for the majority of cyst locations in the patient. IEP was positive in only 73% of cases. The combination of IgG ELISA, IHA, and IgA ELISA allowed us to achieve a sensitivity of 81% in cases of pulmonary echinococcosis. IgE and IgA were both responsible for most nonspecific reactions, the former in patients with parasitic diseases other than echinococcosis and the latter in patients with cirrhosis of the liver and malignancies. IgG ELISA and IHA were the most adequate tests for postsurgical follow-up. In patients with favorable clinical outcome, the specific IgG level decreased early toward the end of the first year, although serological positivity could persist beyond 6 years. A rise of IgG level 2 or 3 years after treatment suggested persistent active infection. In patients with mebendazole associated cure, only tests with total or specific IgE detection seemed to exhibit a strong association with decreasing levels or with negative results. PMID- 1520797 TI - Bactericidal activity of antibiotics alone and in combination against Enterococcus faecalis in a pharmacodynamic model. AB - We evaluated the bactericidal kinetics of teicoplanin, mezlocillin, netilmicin, and ciprofloxacin alone and in dual combinations against strains of Enterococcus faecalis susceptible or resistant to ampicillin in a pharmacodynamic model reproducing in bacterial culture in active human plasma or Mueller-Hinton broth the serum kinetics of these antibiotics in humans. Killing was not different in cultures grown in plasma and those grown in broth. Antibiotics used alone had no or low bactericidal activity except for high-dose ciprofloxacin (600 mg intravenously [iv] twice daily or 750 mg orally twice daily), which achieved a 3- to 4-log reduction in colony-forming units (cfu). Netilmicin was equally active at 6 mg/kg once a day or 2 mg/kg three times daily in all combinations. No major increase in bactericidal activity was detected in any combination that included mezlocillin. Maximal synergistic killing was observed for the combination of teicoplanin plus netilmicin (both at three-times daily and once-daily dosing), which sterilized the bacterial cultures (initial inoculum, 10(6) cfu/mL). Combinations of ciprofloxacin at 600 mg iv twice daily and 750 mg orally twice daily plus either teicoplanin or netilmicin were less synergistic but equally effective in total killing as a result of the high bactericidal activity of ciprofloxacin alone. PMID- 1520798 TI - Mechanisms of resistance to growth inhibition and killing by beta-lactam antibiotics in enterococci. AB - Enterococci are characterized by an intrinsic resistance to growth inhibition by beta-lactam antibiotics. The low susceptibility of enterococci to beta-lactam antibiotics is associated with the synthesis of a particular penicillin-binding protein (PBP) that has a low affinity for beta-lactam agents. This protein appears to be capable of taking over the function of the other PBPs when they are saturated with beta-lactam molecules or inactivated by mutations. A quantitative correlation can be established between the binding of several beta-lactam molecules to the low-affinity PBP and the minimal inhibitory concentration for enterococcal strains. In contrast, the mechanism of enterococcal resistance to the bactericidal activity of beta-lactam agents that inhibit growth at relatively low concentrations appears to be associated with an alteration in the pattern of autolytic enzyme activity. In particular, lack of or poor activity of an autolytic enzyme appears to be responsible for the paradoxical bactericidal response often exhibited by clinical isolates of Enterococcus faecalis in the presence of penicillin. PMID- 1520799 TI - Antibiotic resistance of clinical isolates of Enterococcus in Italy. AB - Alarming reports from various parts of the world of an increase in multiple-drug resistance among enterococci have prompted the Italian Association of Clinical Microbiologists to sponsor a nationwide study aimed at assessing the magnitude of this problem in Italy. During the last 3 months of 1988, technicians from a total of 162 general and teaching hospitals, in 16 of the 20 Italian regions and covering 89,061 beds, isolated 58,886 bacterial strains from inpatients and outpatients. Enterococci (4,879) represented 8.3% of all microorganisms identified, with Enterococcus faecalis accounting for 4,554 strains and Enterococcus faecium for the remaining 316 (6.5% of all enterococci analyzed). Enterococci were recovered most frequently from urine (62.5%) and genitourinary samples (13.7%). Only 58 strains (1.2%) were associated with bacteremia. The in vitro susceptibility of these organisms to 21 commonly used antibiotics is reported and compared with the susceptibility of isolates from a smaller epidemiologic study conducted in Italy in 1986 as well as with more recent findings from individual laboratories. PMID- 1520800 TI - Resistance of enterococci to aminoglycosides and glycopeptides. AB - High-level resistance to aminoglycosides in enterococci often is mediated by aminoglycoside-modifying enzymes, and the corresponding genes generally are located on self-transferable plasmids. These enzymes are similar to those in staphylococci but differ from the modifying enzymes of gram-negative bacteria. Three classes of enzymes are distinguished, depending upon the reaction catalyzed. All but amikacin and netilmicin confer high-level resistance to the antibiotics that are modified in vitro. However, the synergistic activity of these last two antibiotics in combination with beta-lactam agents can be suppressed, as has always been found in relation to high-level resistance to the aminoglycosides. Acquisition of glycopeptide resistance by enterococci recently was reported. Strains of two phenotypes have been distinguished: those that are resistant to high levels of vancomycin and teicoplanin and those that are inducibly resistant to low levels of vancomycin and susceptible to teicoplanin. In strains of Enterococcus faecium highly resistant to glycopeptides, we have characterized plasmids ranging from 34 to 40 kilobases that are often self transferable to other gram-positive organisms. The resistance gene vanA has been cloned, and its nucleotide sequence has been determined. Hybridization experiments showed that this resistance determinant is present in all of our enterococcal strains that are highly resistant to glycopeptides. The vanA gene is part of a cluster of plasmid genes responsible for synthesis of peptidoglycan precursors containing a depsipeptide instead of the usual D-alanyl-D-alanine terminus. Reduced affinity of glycopeptides to these precursors confers resistance to the antibiotics. PMID- 1520801 TI - Modulation of host defenses by cytokines: evolving adjuncts in prevention and treatment of serious infections in immunocompromised hosts. AB - Traditional management of infectious complications, especially in immunocompromised hosts, has depended on the prompt initiation of therapy with broad-spectrum antibiotics. During the past several years, however, a number of cytokines (interleukins, hematopoietic growth factors, interferons) have been developed and produced by recombinant DNA technology, and preclinical and clinical studies of cytokines in immunocompromised hosts have begun. The data being generated suggest that certain cytokines can accelerate neutrophil and monocyte/macrophage production, enhance their function, and potentially decrease infectious complications. The role of these agents in both the prevention and treatment of infectious diseases represents an important research challenge and offers new approaches to the prevention and treatment of infection in immunocompromised hosts. PMID- 1520802 TI - Group A Streptococcus septicemia and an infected, ruptured abdominal aortic aneurysm associated with pharyngitis. AB - A 65-year-old man had a 3-day history of sore throat, fever, rigors, back pain, abdominal discomfort, nausea, vomiting, and diarrhea. The patient's daughter had group A streptococcus pharyngitis. The patient was found to have a ruptured abdominal aortic aneurysm. He underwent resection of the aneurysm and right axillary femoro-femoral bypass graft. The patient died 40 hours after admission. Gram stain of the aneurysm showed numerous gram-positive cocci. Group A streptococcus grew from cultures of blood, throat, and aneurysm. The group A streptococcus was M type 3, T type 3 and produced streptococcal pyrogenic exotoxin A. This case is a very rare fatal complication of group A streptococcus pharyngitis. PMID- 1520803 TI - Fever of unknown origin after Angelchik antireflux prosthesis implantation. AB - The Angelchik device is a silicone collar placed at the gastroesophageal junction for preventing reflux. Many complications associated with the use of this device have been reported, including disruption, migration, and erosion into the gastrointestinal tract. We report another complication of the device, that of abscess formation presenting as fever of unknown origin. This complication emphasizes the need for careful investigation of any implanted foreign body in the evaluation of a patient who has fever of unknown origin. PMID- 1520804 TI - Kingella kingae intervertebral diskitis in an adult. AB - Kingella kingae rarely causes infection and is mainly associated with endocarditis and septic arthritis in adults. The organism is also capable of causing intervertebral diskitis in children, but thus far, no reports of this infection occurring in adults have been published. A case of diskitis due to K. kingae in an adult is reported for the first time, and the literature on this infection in children is reviewed. PMID- 1520805 TI - Transfusion-dependent anemia in a patient with AIDS. PMID- 1520806 TI - Impact of human immunodeficiency virus infection on the epidemiology, clinical features, management, and control of tuberculosis. AB - After years of decreasing prevalence and increasing hope that tuberculosis, like smallpox, could be eliminated, the disease has resurfaced as a major public health problem in the United States. Particularly ominous are the appearance of multiple-drug-resistant strains and their impact on patients and health care workers who are infected with the human immunodeficiency virus, among whom mortality rates reach 80% 2-3 months postdiagnosis. To respond effectively to this new threat, it is critical that we reorient our thinking about tuberculosis and redirect health care resources to programs for tuberculosis control. We need to reinstitute screening of high-risk populations and ensure proper isolation of patients with the disease. Diagnosing tuberculosis at the earliest possible stage is obviously of the utmost importance. High priority must be given to the development of rapid diagnostic tests and techniques that screen for drug resistance. We must implement and adequately fund drug-discovery programs to develop new therapeutic agents that are effective against multiple-drug-resistant strains of Mycobacterium tuberculosis. Effective programs for monitoring the treatment of patients with tuberculosis must also be implemented. Failure to adequately support such programs has probably led to the recent upswing in multiple-drug-resistant tuberculosis, especially in large cities along the eastern seaboard. Leadership for and funding of these programs must come from the federal government, specifically the U.S. Department of Health & Human Services and the Centers for Disease Control (Atlanta). The Infectious Diseases Society of America is actively supporting a variety of tuberculosis control-related initiatives and will keep its members updated on progress in this area.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1520807 TI - Paromomycin in the treatment of mild-to-moderate intestinal amebiasis. PMID- 1520808 TI - Treatment of Paecilomyces varioti infection. PMID- 1520809 TI - Systemic candidal infections in neonates. PMID- 1520810 TI - Colitis due to Candida albicans in a patient with AIDS. PMID- 1520811 TI - Encephalopathy and psychoses associated with sulfadiazine in two patients with AIDS and CNS toxoplasmosis. PMID- 1520812 TI - Fecal carriage of Listeria monocytogenes--observations during a community-wide, common-source outbreak. PMID- 1520813 TI - Relapsing pneumococcal bacteremia in immunocompromised patients. PMID- 1520814 TI - Treatment of cyst passers. PMID- 1520815 TI - Poncet's disease: case report. PMID- 1520816 TI - Tuberculous abscess in a patient with AIDS. PMID- 1520817 TI - Aseptic meningitis following administration of intravenous immune globulin. PMID- 1520818 TI - Community-acquired bacteremia due to multiresistant Enterobacter in a patient with urosepsis. PMID- 1520819 TI - Concurrent infection with multiple strains of Salmonella typhi. PMID- 1520820 TI - Disseminated sporotrichosis in a patient infected with human immunodeficiency virus. PMID- 1520821 TI - Septic arthritis caused by Bacteroides fragilis in the setting of postlithiasis pyelonephritis. PMID- 1520822 TI - Isolation of Chlamydia pneumoniae from the maxillary sinus of a patient with purulent sinusitis. PMID- 1520823 TI - "Sauriasis": even immunoincompetence has limits. PMID- 1520824 TI - Re-evaluation of the biocompatibility of bioinert ceramics in vivo. AB - The affinity of bone for bioinert ceramics and stainless steel was compared using calcified bone specimens. We implanted cylinders of alumina ceramics (Al2O3), zirconia ceramics (ZrO2) and SUS-316 L stainless steel into the distal femoral epiphyses of dogs and then made observations from 4 to 96 wk post-operatively. Irregularities in the histological specimens suggested the presence of artefacts due to the insertion technique. We subsequently used screws inserted into holes tapped with a tap that had a diameter identical to the screws, and observed these implants from 4 to 96 wk after insertion. There was no detectable difference in the affinity index for all three materials from 4 to 96 wk after implantation. The affinity index was calculated as the ratio of the new bone directly adjoining the implant without any intervening fibrous membrane or bone marrow to the total length of the bone-implant interface x 100%. PMID- 1520825 TI - Comparative biophysical study of adsorbed calf serum, fetal bovine serum and mussel adhesive protein films. AB - Varying concentrations of different sera and adhesive agents are routinely used to increase cellular attachment to substrata. The surface-chemical effects of some of these surface-altering materials have been examined using ellipsometry, contact angle analysis and multiple-attenuated internal reflection infrared (MAIR IR) spectroscopy. Specifically, 15% fetal bovine serum (FBS), Ham's F-12 (containing 10% FBS + 1% penicillin/streptomycin), 10% calf serum and mussel adhesive protein (MAP) were allowed to adsorb on to similar and different surfaces and then compared. Each of these preparations is capable of altering the surface-chemical properties of substrata with varying resultant surface energies. It is therefore important to characterize serum in the proper concentrations on the substrata under consideration in order to understand the interfacial effects. PMID- 1520826 TI - Cellular reaction to the Vascugraft polyesterurethane vascular prosthesis: in vivo studies in rats. AB - The biocompatibility of Vascugraft, a polyesterurethane vascular prosthesis manufactured by Braun-Melsungen AG, was assessed by immunofluorescence and histological studies. Discs, 1 cm2, of Vascugraft prosthesis were implanted into the peritoneal cavity of rats. Results were compared with Impra, GORE-TEX and Mitrathane prostheses and a control group. Animals were killed at 1, 2, 6, 9 and 12 wk. Total T cells, T helper cells, T suppressor cells and activated T lymphocytes expressing Interleukin-2 receptors were quantified by a cytofluorometric technique in the peripheral blood of rats. For each period of implantation, all vascular prostheses showed no significant change in the percentage of total T cells, T subsets and T cells expressing Interleukin-2 receptors when compared to the control group. Histological examination of the tissue reaction surrounding the Vascugraft revealed a mild inflammatory reaction, similar to the one observed with both polytetrafluoroethylene grafts. However, the rate and the degree of encapsulation were different between grafts. The Vascugraft prosthesis was well encapsulated 2 wk after implantation, whereas inhibition of fibroblastic proliferation into the graft wall and surrounding both polytetrafluoroethylene grafts was observed for each period of implantation. The Mitrathane prosthesis exhibited a moderate inflammatory response, characterized by a high level of activation on fibroblasts compared to other grafts. PMID- 1520827 TI - Effect of lithotriptor treatment on the fracture toughness of acrylic bone cement. AB - Extracorporeal shock wave lithotripsy (ESWL) has now been established as an efficacious non-invasive modality for the management of renal calculi and has shown promise for management of other types of stone, as well. Following on from these successes, ESWL has recently been proposed for use in the preliminary stages of revision of cemented total hip joint replacements as a means of breaking up the cement mantle. It is useful, therefore, to examine the effect of shock waves on pertinent mechanical properties of the cement. This study utilizes the chevron-notch short-rod specimen and a commercially available test system to obtain the values of one such property, namely fracture toughness, of Palacos Radiopaque bone cement before and after treatment with shock waves delivered from a lithotriptor. The fracture toughness drops by about 14% following the shock wave treatment, thus confirming the possibility that ESWL can be used, as indicated earlier, in revision arthroplasty. PMID- 1520828 TI - Controlled cisplatin delivery system using poly(D,L-lactic acid). AB - Cisplatin (CDDP)-containing poly(D,L-lactic acid) microspheres (CDDP-MS) and beads (CDDP-B) with an average molecular weight of the oligomer of 1.2 x 10(4) and 4% CDDP loading were prepared. In Tris buffer, 95% of CDDP disappeared from CDDP-MS within 3 d. In vitro and in vivo, CDDP-B released CDDP for 30-57 d, and for 21-42 d, respectively. The other CDDP-B with an average oligomer molecular weight of 9.6 x 10(3) with 5% lactic acid monomers, that contained 4% CDDP, showed a two-phase CDDP release pattern and CDDP disappeared within 41 d in vitro, and within 21 d in vivo. Histologically, tissue necrosis surrounding the CDDP-B was not severe. PMID- 1520829 TI - Improvement of blood compatibility on cellulose dialysis membrane. 2. Blood compatibility of phospholipid polymer grafted cellulose membrane. AB - The blood compatibility of a cellulose haemodialysis membrane whose surface was grafted with a methacrylate having a phospholipid polar group, 2 methacryloyloxyethyl phosphorylcholine, was evaluated with attention to platelet adhesion to the membrane surface and complement activation induced by the membrane. When the original cellulose membrane came in contact with platelet-rich plasma for 30 min, numerous platelets adhered to the surface and aggregated. On the other hand, the membrane grafted with 2-methacryloyloxyethyl phosphorylcholine effectively suppressed platelet adhesion and activation. This effect became more pronounced with increasing surface distribution. Especially, the 2-methacryloyloxyethyl phosphorylcholine grafted membranes, whose distribution exceeded 0.27, completely inhibited platelet adhesion, even when the contact time was 180 min. Moreover, the complement activation was also reduced with increased 2-methacryloyloxyethyl phosphorylcholine distribution on the surface of the membrane. PMID- 1520830 TI - Degradation of five polyurethane gastric bubbles following in vivo use: SEC, ATR IR and DSC studies. AB - Five Garren-Edwards Gastric Bubbles were characterized, following up to 4 months use in vivo, using size exclusion chromatography, differential scanning calorimetry and attenuated total reflectance infrared spectroscopy. These techniques show that the material used to construct the bubble is probably an aromatic polyester urethane and revealed a 39-55% decrease in number average molecular weight, a 9 degrees C decrease in glass transition temperature, the disappearance of soft segment crystallinity and a broadening of the hard segment melting region after exposure to highly acidic (approximately pH 1.2) gastric fluid. The results indicate that significant chemical and morphological changes have taken place in the bubble material, including loss in chemical functionality, phase separation and increased hard segment aggregation. A comparison of the decrease in glass transition temperature as a function of molecular weight suggests that glass transition temperature is a sensitive predictor of this material's stability. Additionally, evidence is provided that the broad infrared absorption at 1077-1067 cm-1 normally assigned to C-O-C hard segment may represent two types of C-O-C stretching: (1) C-O-C stretching of the free urethane carbonyl, and (2) C-O-C stretching of the hydrogen bonded urethane carbonyl. PMID- 1520831 TI - Structure, solubility and bond strength of thin calcium phosphate coatings produced by ion beam sputter deposition. AB - Ion beam sputter deposition was used to produce thin calcium phosphate coatings on titanium substrates. Structure, solubility and bond strength of the as sputtered and heat treated coatings were evaluated. X-ray diffraction (XRD) analysis of the heat treated coatings revealed a hydroxyapatite-type structure. The heat treated coatings were found to have significantly lower solubility as compared to the amorphous as-sputtered coatings. Although the crystalline coatings exhibited the lowest solubility, in general, the bond strengths were lower for the heat treated coatings. PMID- 1520832 TI - Effect of titanium implants on primary mineralization following 6 and 14 days of rat tibial healing. AB - The effect of pure commercial titanium implants on the process of primary mineralization was studied. This was examined by insertion of titanium implants into rat tibial bone after ablation. The effects of the titanium were studied through the behaviour of extracellular matrix vesicles (MV). Methods of morphometric analysis at the TEM level were applied. The insertion of titanium implants was followed by an increase in the number of MV as well as vesicular diameter and by a decrease in vesicular distance from the calcified front when compared to normal healing. These results suggest that the process of MV maturation around titanium implants was delayed when compared to normal primary bone formation during bone healing. The delay in mineralization was compensated by an increase in vesicle production, resulting in an enhancement of primary mineralization by the titanium. PMID- 1520834 TI - Special issue on comparative oncology. PMID- 1520833 TI - Inflammatory response to subcutaneously implanted Marlex and GORE-TEX in massively obese patients. AB - In both vertical banded gastroplasty and in gastric banding, synthetic bands are used to reinforce the outlet from the pouch to the rest of the stomach. Two materials commonly used for these bands are polypropylene (Marlex) and polytetrafluoroethylene (GORE-TEX). As a measure of their suitability, human inflammatory response to subcutaneous implants was investigated. In a randomized series of 17 superobese patients a patch of GORE-TEX was implanted subcutaneously in one groin under local anaesthesia and Marlex mesh was implanted in the other groin. After about 2 months the implants were exstirpated and investigated in a single blind procedure by an experienced pathologist. Marlex gave a significantly greater chronic inflammatory reaction and fibrosis than GORE-TEX. The foreign body giant cell reaction was, however, significantly greater with GORE-TEX. The possible implications of these results are discussed. PMID- 1520835 TI - Regulation of tumor cell growth at organ-specific metastases. AB - The hallmark of malignant neoplasms is their ability to spread beyond the site of origin and produce metastases in distant organs. This nonrandom process depends on the interaction of specific tumor cells with a compatible milieu provided by a particular organ microenvironment; the molecular basis of which is under intense investigation. Recent analysis of human colon carcinoma (HCC) cells obtained from surgical specimens and implanted into athymic nude mice suggested that whereas nonmetastatic and highly metastatic cells can grow at local sites, growth per se in the secondary organ-specific site was associated only with high-metastatic HCC cells. These cells also respond in a specific manner to physiological mitogenic signals produced by damaged normal tissues. This article addresses the biological and molecular evidence supporting the hypothesis that organ-derived, perhaps, organ-specific, paracrine growth factors stimulate the growth of receptive malignant cells that possess the appropriate receptors. PMID- 1520836 TI - Comparative aspects of the quality of life in cancer patients. AB - Chronologically, neoplastic diseases can be divided into two categories of which the first includes the fast and aggressive disease groups which exhibit a short course after the diagnosis has been established and the second those with dormancy or a slow path of which the development extends over years, even decades. The developed treatment modalities have even expanded the time duration of both groups, and thus cancer has become a group of chronic diseases in many cases. This requires a special adaptation in regard to the life style and quality of the cancer patient. The assessment of the quality of life in the cancer patient has been evaluated through questionnaire to relatives and friends as well as through social experience with cancer patients. The diversity of the disease group is reflected in the need for a more heterogeneous improvement of life style and its quality according to the need of the patient groups. A distinction can be made between acute and chronically ill pediatric patients, the cancer patient who is able to continue his work, the outpatient not requiring hospitalization, the patient with the need for hospital care (for a shorter or longer Period), the hospice patient, the elderly patient, and the terminally ill patient as well as the patient in the last days of life. In a study of 1,227 elderly decedents in Fairfield County, Connecticut, for which 260 respondents reported cancer as the cause of death, approximately 1/5 were reported to have been in moderate or severe pain six hours before death, with little change from the previous month.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1520837 TI - Report of dysgerminoma in the ovaries of a snapping turtle (Chelydra serpentina) with discussion of ovarian neoplasms reported in reptilians and women. AB - A malnourished, captive, young adult (weight-11 kg, carapace length-25 cm), female snapping turtle (Chelydra serpentina) was presented for examination and treatment of malnutrition and multiple carapace necroses. Because treatment was unsuccessful, the animal was euthanatized and necropsied. The main necropsy observations showed the presence of a 9 cm greyish-white/yellow, soft, fleshy to fatlike mass involving the right ovary near the oviduct opening and multiple similar, pea-to-walnut sized masses involving both ovaries. Microscopic examination of formalin fixed, hematoxylin and eosin and silver stained tissue sections revealed the masses to be composed of primordial germ cells arranged in a pattern morphologically compatible with dysgerminoma as described in women and other mammals. Very rarely have ovarian neoplasms been reported in turtles or other reptiles. This is the first neoplasm described in the snapping turtle ovary and the first dysgerminoma reported in reptilians. A tabulation of previously documented ovarian neoplasia in reptiles and a comparison of this cancer to those occurring in women will be discussed. PMID- 1520838 TI - Longevity of mammals in captivity--an update. AB - The life span of the various mammalian species differs and is an important parameter in comparative oncology; it should always be expressed as a percentage in relation to the potential life span of each species investigated. Mammals are a highly heterogenous class of animals. This heterogeneity is also reflected in a random variation of their life span by species. PMID- 1520839 TI - Transmission studies of sarcoma in the soft-shell clam, Mya arenaria. AB - Transmission experiments with adult soft-shell clams (Mya arenaria) demonstrated that clam sarcomas are transmissible with hemolymph from neoplastic animals but not with cell-free ultrafiltrates. Non-neoplastic clams were injected with either hemolymph from neoplastic clams or a cell-free ultrafiltrate prepared from a subsample of the same hemolymph. Injected clams were held in separate flow through aquaria and examined for sarcomas by histocytology and histology. Data at 17 weeks showed a 44% prevalence of sarcomas in clams injected with neoplastic inoculum. No sarcomas were observed either in clams injected with a cell-free ultrafiltrate or in the control animals. The lack of sarcomas in clams injected with the ultrafiltrate argues against a viral etiology for the disease. PMID- 1520840 TI - Optimization of the chronotherapeutic index in the experimental animal laboratory. AB - Large animal studies show that the effects of fixed doses of anticancer drugs vary predictably with multi-frequency rhythms' stages--components of a genetically--anchored, habitat synchronized, cosmically influenced time structure -the chronome. Both the tolerance by the host of the toxic drugs and the treatment's efficacy in killing cancer cells contribute to these changes. Chronotherapy, timing treatment according to the chronome, attempts to first maximize treatment efficacy while also minimizing toxicity, so as to optimize the therapeutic ratio. Outcomes have been improved by several hundred per cent by treating rodents at the "right" time with single or multiple agents under controlled laboratory conditions, and by chronoradiotherapy of human perioral tumors, using tumor temperature as a marker rhythm. PMID- 1520841 TI - Chronobiologic response modifiers and breast cancer development: classical background and chronobiologic tasks remaining. AB - Mapping the chronome's multi-frequency (about-daily, -weekly, and -yearly) neuroendocrine and immune rhythms can help determine when potential chronobiologic response modifiers (CBRMs) should be applied. Aimed at shielding in time by manipulating rhythms, CBRMs may be pertinent to all stages of carcinogenesis, from prevention to treatment, by forestalling the neuroendocrine, immunologic or cell cycle-related recurrent susceptibility peaks from getting aligned, favoring cancerous growth. Pituitary/hypothalamic isografts in the virus free Bagg albino mouse and designs described as heterophasic allow the systematic investigation of the effect of internal shifts among neuroendocrines. Rhythm manipulation by CBRMs can then aim at lowering (breast or prostate) cancer risk by reproducing identified favorable low risk chronome configurations such as a circannual amplitude in blood that is small for TSH and large for prolactin in women and vice versa for men. PMID- 1520842 TI - From experimental units to unique experiments: chronobiologic pilots complement large trials. AB - The timing of treatment affects outcome. For mapping multi-frequency rhythm spectra first to optimize chronochemotherapy, 1000 marker determinations on the subject are more informative than a few determinations on each of hundreds of patients. N-of-6 subgroups should follow, with one subject assigned to each of 6 marker rhythm stages, 60 (e.g. 4 hours on a 24-hour scale) apart. Once the time structure has been mapped, minimal sampling requirements determined, and guidelines for treatment established, the information gained from chronobiologic n-of-1 and n-of-6 test pilot designs can be built cost-effectively into randomized controlled trials to benefit large patient populations. Sequential tests combined with marker rhythmometry and cosinor analysis on single test subjects, small groups and eventually on each patient are powerful tools that can extract information otherwise unattainable even at great cost and bring the P value from publications to the patients. PMID- 1520843 TI - Black and white differences: narrowing the gap in cancer medicine. AB - Excess mortality is a complex problem involving multiple sub-problems including culture, economics, lifestyle, issues related to cancer biology, and access to medical care among other issues. Consideration has to be given to the multiple influences that lead to this discrepancy in survival related to cancer and the increased incidence of certain tumors. Increased availability of state-of-the-art cancer treatment to the population as a whole will upgrade the level of care by those that participate in clinical trials; the physicians and finally even those patients who are not entered into the trials. Upgrading the access to information about prevention and control of cancer is of equal importance. There are those tumors with possible biological explanations for increases in cancer incidence in the Black population, in particular, multiple myeloma and prostate cancer. There are tumors which are increasing in incidence in this population with no explanation but which must relate to biological factors. PMID- 1520844 TI - Amphibian tumors: a comparison of anurans and urodeles. AB - Anuran and urodele amphibians develop spontaneous neoplasms in all major organ systems with the integumentary system a frequent target. Anurans and urodeles have spontaneous viral-associated tumors, the biological behavior of which is temperature-related. Anurans seem to have a greater frequency of spontaneous neoplasms than do urodeles and respond to chemical carcinogens in a manner analogous to mammalian species. Urodeles have greater cell regenerative capabilities than do anurans and paradoxically, are more refractory than anurans or mammalian species to chemical carcinogens in their proliferating regenerative blastema. PMID- 1520845 TI - Nature and frequency of bony tumors in prehistoric and historic populations. AB - The skeletons of the Merovingian population from Kleinlangheim (Southern Germany) were examined by macroscopic, radiological, endoscopic and microscopic techniques. In about 6% skull tumors could be diagnosed. All five cases reported here are examples of benign tumors. Three of these are tumors of the paranasal sinuses. A connection between sinusitis and fibro-osseous tumors of the paranasal sinuses is suggested. The etiology of these tumors and methods of diagnosis of tumors in archaeologic bone are discussed. PMID- 1520846 TI - The possible role of the initial lymph vessels of the skin during metastasis of malignant tumors. AB - The metastasizing potential of a malignant tumor is derived primarily from its biological characteristics. The second most important factor in metastatic spreading lies in the host tissue/organ and host metabolism. The aggressiveness of a malignant skin melanoma depends clinically upon the width and, especially, the depth of the preceding lesions(s). Histological and electron microscopic studies reveal that the increase of malignant aggressiveness is directly related to the arrangement of the initial lymphatic vessels in the different layers of the skin. Sudden increase in the density of lymphatic vessels permits a corresponding increment of malignant seeding via the lymphatic system. PMID- 1520847 TI - Comparison of arteriosclerosis, neoplasms and diabetes as the three main killers of man in the industrialized world. AB - Arteriosclerosis, neoplasms and diabetes are the three main killers in the industrialized world, complemented by infectious and parasitic diseases in the less developed countries. Neoplasms, the second most frequent killer in the industrialized world, exhibit the highest diversity of pathologic structures involved. Arteriosclerosis, the first killer in the industrialized world, is more complex, dealing with aberrations of the arterial wall. In contrast to neoplasms, cases are restricted to a closed circulatory system as noted in the various phyla. Neoplasms are also known from the kingdom of plants and fungi, whereas arteriosclerosis is restricted to specific animal phyla, at least theoretically. Even more restricted is the distribution of diabetes which is known only in certain vertebrates. All three disease groups have a substantial impact on man's health. PMID- 1520848 TI - Changes in the course of cancer. AB - Many neoplasms cannot be cured but the life span of the patient afflicted with such diseases has in a remarkable number of cases been prolonged. The course of neoplastic diseases has been changed, improving life-style and survival on the one hand, but resulting in new side effects including multiple primary neoplasms on the other. In contrast to neoplastic diseases with aggressive acute development, we can observe an increasing number of neoplastic diseases with a chronic, prolonged that progress. To understand this it is necessary to remember that neoplastic diseases are heterogenic in nature, and also diseases of autonomic growth comprising modification of the host along with progression of the tumor. PMID- 1520849 TI - Some characteristics of the mesenchymal stem cell of soft tissue tumors. AB - "Soft tissue tumors" is an unnatural term, used by clinicians and for convenience by pathologists, which unites the neoplasms of mesenchymal origin as opposed to those of the soft epithelial tissues. Not included are the reticuloendothelial system, glia and supporting tissues. The mesenchymal stem cell, the cell of the embryonal connective tissue, exhibits in man and mammals the most pronounced embryonal potential. A restricted comparison to the embryonal potential in larval and pupal cells of invertebrates, such as in hemi- or holometabolic insects and to meristematic cells in vascular plants is justified. The great embryonal potential may explain why the mesenchymal stem cell, at present a hypothetical unit, is able to transform and differentiate into the connective tissue as such, the muscular, supporting and hematogenic tissues. The musculature comprises the bulk of the mammal's body weight. The development of the normal ontogenetic specialization as well as especially those differentiations leading to soft tissue tumors are comparatively shown in this publication and placed in the framework of vertebrate and invertebrate animals with true tissues. PMID- 1520850 TI - American Society of Nephrology, 25th annual meeting. Baltimore, Maryland, November 15-18, 1992. Abstracts. PMID- 1520851 TI - Fos expression in the trigeminal sensory nuclei after a chemical lesion of the lower lip mucosa. AB - C-fos containing neurons were investigated in the trigeminal sensory nuclear complex and in the dorsal horns of the cervical spinal cord (C1-C2) of the rat after a chemical noxious stimulus was applied to the lower lip mucosa. Numerous labelled neuronal nuclei were detected in the dorsolateral area of the caudal half of the trigeminal nucleus interpolaris, and in Rexed's laminae I-IIo of the dorsomedial area of the trigeminal nucleus caudalis and rostral C1. A few c-fos labelled neurons were observed in laminae IIi and V. No Fos expression was detected in the trigeminal oral and principal nuclei. PMID- 1520852 TI - Production of antiserum to [D-Ala2]deltorphin I and its immunohistochemical application to the mouse brain. AB - Antiserum to haptenic [D-Ala2]deltorphin I (DADTI: Tyr-D-Ala-Phe-Asp-Val-Val Gly.NH2), a highly selective ligand for delta opioid receptors, was produced in rabbits. By immunospot assay, the antiserum recognized 62.5 pmol DADTI but failed to react even with 4 nmol carrier protein of the immunogen. Although the antiserum reacted equally with an isomer [L-Ala2]deltorphin I, virtually no cross reaction occurred with other analogues such as [D-Ala2]deltorphin II (Tyr-D-Ala Phe-Glu-Val-Val-Gly.NH2) and similar peptides lacking the C-terminal glycine amide. Therefore, the major epitope for immunorecognition appeared to be in the C terminal region which is known to be the specific domain for delta opioid receptor selectivity. Immunohistochemical study using this antiserum revealed positive neuronal structures in some specific systems of the mouse brain. PMID- 1520853 TI - Somatosensory input and thalamic projection of pedunculopontine tegmental neurons. AB - The cholinergic pedunculopontine tegmental area of the anesthetized rat was explored for single units responsive to somatosensory stimulation. Units projecting to the intralaminar thalamus were identified by antidromic stimulation. Approximately one half of the somatosensory units consisted of low threshold units responsive to light tapping and stroking; the others were high threshold mechanoreceptive units. Most receptive fields were trigeminal and contralateral. These results suggest that somatosensory information is an important element in a subcortical system linking this area with the basal ganglia, superior colliculus and thalamus. PMID- 1520855 TI - Postsynaptic potentials in cat visual cortex: dependence on polarization. AB - During the investigation of visually evoked postsynaptic potentials (PSPs) of visual cortical neurons, we recorded cell activity under different levels of membrane potential. In some cases, however, dependence of these PSPs on the level of membrane polarization appears to be inconsistent with the conventional scheme. One disagreement was the reduction, instead of an increase, of excitatory potentials during hyperpolarization of the cell. The other point was that depolarization of the cell often leads to increase of the amplitude of both excitatory and inhibitory postsynaptic potentials. This inconsistency may suggest the involvement of voltage-dependent ion channels in generating PSPs to visual stimuli. A possible way of separating the excitatory and inhibitory components of the response by polarization of the cell in spite of the presence of voltage dependent channels and possible implications of this mechanism in the visual cortex are discussed. PMID- 1520854 TI - Effect of REM sleep deprivation on molecular forms of acetylcholinesterase in rats. AB - Since REM sleep deprivation was reported to increase the activity of acetylcholinesterase, an attempt was made to investigate whether the different forms of enzyme could be affected selectively. The flower pot method was used for deprivation and suitable control experiments were conducted. The bound and the soluble forms, if affected would show an increase or a decrease, respectively, on REM deprivation. The former is affected first in the pons while the latter in the medulla. The findings support the pontomedullary cholinergic mechanism for the generation of REM sleep. Though there may be a possibility of conversion of the free to the bound form, the increase in the latter was more than the decrease in the former. PMID- 1520856 TI - Propagation of colour information across borders. AB - When a part of an image is stabilized on the retina, the part fades to the same colour as its unstabilized surround. The apparent colour of an empty field is therefore assumed to be equal to the colour of its borders. Here, we will show that a similar phenomenon can take place even when the border of a centre field is still visible. A grey square patch with a black frame was surrounded by a coloured background. When the frame had such crossed disparity that the frame appeared in front of the patch, the colour of the patch became perceptually similar to that of the background, indicating that the colour of an empty field is not determined by the colour of its borders alone. PMID- 1520857 TI - CCKB receptor stimulation mediates [Ca2+]i increase but no PKC activation in Jurkat T-cells. AB - We have investigated the effect of cholecystokinin-octapeptide (CCK-8) on [Ca2+]i and protein kinase C (PKC) activity in Jurkat T-cells. CCK-8 produced a transient [Ca2+]i increase in the presence of extracellular Ca2+. While CCKB receptor antagonist L-365,260 abolished the elevation of [Ca2+]i, CCKA receptor antagonist L-364,718 was without effect. Moreover, the dihydropyridine calcium channel blocker nitrendipine was shown to block the observed calcium response. Results suggest that the calcium effect is caused by an interaction of CCK-8 with CCKB binding sites and an influx of external Ca2+ via dihydropyridine sensitive calcium channels might serve as a source for the increased [Ca2+]i. Because CCK-8 induced no PKC activation CCKB receptor mediated rise of intracellular calcium seems not to include activation of phospholipase C. PMID- 1520858 TI - Suppression of audiogenic epileptic seizures by intracerebral injection of a CCK gene vector. AB - P77PMC rat is a breed of rat with congenital audiogenic seizure (AS). AS attacks could be suppressed by cholecystokinin octapeptide (CCK-8) injected intracerebroventricularly (i.c.v.). In the present study we made i.c.v. injection of plasmid pSV2-beta Gal or pSV2-CCK encapsulated with lipofectin. Expression of pSV2-beta Gal in brain occurred from d 1 to d 14, with maximal expression at d 3 and d 4. After i.c.v. injection of pSV2-CCK plasmid, the AS of the P77PMC rats was markedly reduced, which was most obvious at d 3 and d 4. The time course of the AS repression was almost identical with that of pSV2-beta Gal expression. The results suggest that the repression of the AS in P77PMC rats is accounted for by the expression of foreign CCK gene in brain tissue. PMID- 1520859 TI - Angiotensin AT2 receptors regulate cerebral blood flow in rats. AB - LARGE cerebral arteries have been reported to contain angiotensin receptors that are exclusively of the AT2 subtype. We measured the effect of the AT2 receptor selective ligand PD 123319 on cerebral blood flow (CBF) in rats, using laser doppler flowmetry. PD 123319 (1-10 mg kg-1) dose-dependently inhibited the increase in CBF, when the blood pressure was increased by a norepinephrine infusion. However, PD 123319 did not alter baseline CBF at normal blood pressures. Therefore PD 123319 appears to interfere with the autoregulatory mechanisms of CBF. The participation of AT2 receptors in the regulation of CBF confirms a physiological role for this receptor subtype, and may give clues for future treatment of various cerebrovascular disorders. PMID- 1520860 TI - Calcium-mediated neuronal degeneration following singlet oxygen production. AB - NONINVASIVE photolytic injury to targeted neuronal subpopulations in vivo causes unique, slowly progressive neuronal degeneration. To examine the mechanisms of degeneration toward development and transplantation studies, cytosolic calcium levels were measured in vitro from neocortical neurons after incorporation of photoactive nanospheres and laser-activated singlet oxygen production within lysosomes. Cytosolic calcium increased irreversibly, predominantly from extracellular sources through channel-mediated mechanisms and increased membrane porosity. Propidium iodide studies demonstrated gradual loss of membrane integrity over hours to days. The calcium channel blocker nimodipine, or calcium free medium, partially protected neurons from calcium flux and cell death. Results suggest calcium-dependent and independent mechanisms of neuronal degeneration following singlet oxygen production. PMID- 1520861 TI - Dendritic regrowth of retinal ganglion cells in adult rats. AB - IN adult rat retinal ganglion cells, we investigated how their dendrites are maintained during axonal regeneration induced by a peripheral nerve (PN) graft. Intracellular Lucifer Yellow injection revealed that rapid dendritic retraction occurred immediately after axotomy and grafting. However, dendrites that probably sprouted after axotomy were often found in the regenerating ganglion cells, and their dendritic field tended to recover in area by 3 months after grafting. Although such dendrites were also found in an axotomized cell receiving no PN graft, they are much more frequently observed in the regenerating cells. Therefore, a PN graft can facilitate the rat ganglion cells to regrow their dendrites. PMID- 1520862 TI - Age-related shrinkage of the mamillary bodies: in vivo MRI evidence. AB - Mamillary body (MB) is a diencephalic structure hypothesized to be involved in memory, a cognitive function that declines with age. In this study, age-related differences in the size of MB were examined in vivo using magnetic resonance (MR) imaging. The cross-sectional area of the MB was estimated from MR images of the brain in healthy volunteers and neurologically intact patients (age 18-78). The cross-sectional area of the tectum was used as a control region of interest. We found a significant age-related reduction in the area of the MB, but not of the tectum. No sex differences were observed in the size of either structure. PMID- 1520863 TI - Mnemonic and predictive functions of cortical neurons in a memory task. AB - Single-neuron discharge was recorded from prefrontal and posterior parietal cortex in monkeys performing a visuo-motor memory task with temporal and spatial separation between cue (color) and directional manual response. During the delay interval between cue and response, neurons in both cortices engaged in two concurrent and reciprocal trends of discharge: (a) sensory-coupled, decelerating firing apparently related to color retention, or (b) motor-coupled, accelerating firing apparently related to the anticipated response direction. In both cortices, the acceleration of the direction-anticipating activity was related to the probability with which the animal could predict, and prepare for, the correct response site. Our findings suggest that neurons from prefrontal and parietal cortex are part of distributed networks, with representational and operational properties, for visuomotor cognitive processing. PMID- 1520864 TI - A behavioral study of bilateral middle cerebral artery hemorrhagic ischemia in rats. AB - The middle cerebral artery was severed bilaterally (bMCA) in adult rats, and controls experienced sham operations. Tactile sensorimotor and gross locomotor functions, measured by the tape test and a rod walking test, were initially impaired in the injured animals. However, these deficits had resolved within 9 and 30 days respectively. The animals were trained in a multiple T water maze task to find the location of a hidden escape platform at the rate of one trial per day for 30 days. Analyses of the number of errors committed and latency to find the escape platform revealed that the bMCA injured rats suffered deficient reference memory, but no decline in working memory. These data support further the use of the bMCA preparation as a model of stroke. PMID- 1520865 TI - Bone marrow transplantation for thalassemia and other inherited disorders of hemoglobin. PMID- 1520866 TI - The molecular immunology of human platelet proteins. PMID- 1520867 TI - Unexpected heterogeneity in E2A/PBX1 fusion messenger RNA detected by the polymerase chain reaction in pediatric patients with acute lymphoblastic leukemia. AB - The t(1;19)(q23;p13) is the most common recurring chromosomal translocation in childhood acute lymphoblastic leukemia (ALL) and has been associated with adverse prognosis. It involves the rearrangement of two genes, PBX1 and E2A, resulting in the production of transforming chimeric DNA-binding proteins. In all previous reports in which the presence of a chimeric transcript was described, the fusion point between the coding sequences of E2A and PBX1 was found to be constant at the RNA level. We have used RNA-based polymerase chain reaction (PCR) for the detection of E2A/PBX1 messenger RNAs (mRNAs) in children with ALL at the time of diagnosis. Of 21 patients exhibiting this rearrangement, 3 (14%) expressed a variant E2A/PBX1 transcript in addition to the expected one. The relative amounts of the two chimeric mRNAs varied between the patients, but remained constant in the same patient during different stages of the disease. Sequence analysis showed an identical insertion of 27 bp at the E2A/PBX1 junction of the variant RNA species, the translation of which would result in the replacement of Val478 by 10 amino acids. The inserted sequence has not been detected in any other human transcript besides the variant E2A/PBX1 RNA species and probably represents a splicing variant of the chimeric RNA. We conclude that a subset of pediatric patients with ALL that carry the E2A/PBX1 rearrangement express two types of the chimeric mRNA. The biologic significance of this additional E2A/PBX1 transcript is discussed. PMID- 1520868 TI - Human peripheral blood hematopoietic progenitors are optimal targets of retroviral-mediated gene transfer. AB - Hematopoietic progenitor cells circulate in the peripheral blood (PB) of cancer patients during the recovery phase that follows treatment with high-dose cyclophosphamide followed by hematopoietic growth factor infusion. We report that when PB progenitors were exposed in vitro to filtered supernatant from cell line PA317-N2, producing amphotropic helper-free N2 vector at conventional titers, successful retroviral-mediated transfer of neomycin resistance gene was documented by polymerase chain reaction in 93% of day 14 myelomonocytic colonies. Under the same conditions, gene transfer was achieved in 22% of steady-state bone marrow-derived myelomonocytic colonies. Neo-resistance gene transfer was documented also in a CD34+/cyclophosphamide-resistant precursor to granulocyte macrophage colonies, an undifferentiated progenitor close to the hematopoietic stem cell. Neither cocultivation with vector-producing cells nor high vector titer were stringent requisites for efficient gene transfer. The large-scale availability of PB hematopoietic progenitors in cancer patients, together with the high gene transfer rate achieved under safe and clinically feasible conditions, support an optimal approach for gene transfer procedures into the human hematopoietic system. PMID- 1520869 TI - Autologous bone marrow transplantation in acute leukemia with marrow purged with alkyl-lysophospholipid. AB - Alkyl-lysophospholipids are anticancer agents that are selectively toxic to leukemic cells and relatively sparing of normal bone marrow cells. Thus, they would be likely candidates for purging remission marrows before autologous bone marrow transplant. One of the more promising agents is edelfosine, which could be safely used for purging without prolonging marrow recovery. Assays for marrow progenitor cells were performed before and after purging and cryopreservation in 64 patients. There was no significant reduction in colony formation after purging when compared with unpurged cryopreserved marrow, but there was a significant reduction after cryopreservation. Twenty-four patients with acute leukemia in second (16 patients) or third remission (3 patients), early relapse (3 patients), or in first remission with successfully treated extramedullary relapse (2 patients) received marrow-ablative chemotherapy and total body irradiation followed by infusion of marrow purged for 4 hours with 50 to 100 micrograms/mL of edelfosine. There were 9 lymphoblastic and 15 myelogenous leukemia patients. The median time to granulocyte recovery to 500/microL was 26 and 33 days for the 50 and 75 microgram/mL doses, respectively. The patient whose marrow was purged at the dose of 100 micrograms/mL failed to engraft. The median time to platelet recovery to 25,000/microL was 45 and 37 days for the 50 and 75 micrograms/mL doses, respectively. Twenty-nine percent of the patients remain disease free from 131 to 1,291 days, with a median of 356 days. These results have established that purging with 75 micrograms/mL of edelfosine is a safe dose and is recommended for a phase II trial. PMID- 1520870 TI - Use of alpha interferon for the treatment of relapse of chronic myelogenous leukemia in chronic phase after allogeneic bone marrow transplantation. AB - Eighteen patients with relapse of chronic myelogenous leukemia (CML) after allogeneic bone marrow transplantation (BMT) were treated with recombinant human alpha 2a interferon (IFN). Relapse was defined as greater than 90% metaphases containing the Philadelphia chromosome (Ph) and hematologic abnormalities consistent with chronic-phase (CP) CML. There were 11 males and seven females, with a median age of 38 years (range, 3 to 55). Three patients relapsed after second BMT. Only one patient had received T-cell-depleted marrow initially. The initial IFN dose of 3 x 10(6) U/m2/d was escalated to the maximum tolerated dose or to a maximum of 6 x 10(6) U/m2/d. IFN controlled the white blood cell (WBC) counts in 14 of 16 patients who had abnormal counts, and in all six patients with an elevated platelet count. Six patients (33%) have had a complete disappearance of the Ph and two have had a partial response (less than 35% Ph+ metaphases). One patient has a decrease in Ph+ metaphases after 9 months of IFN. Five patients had no significant cytogenetic response after 9 to 12 months, and four developed clinical accelerated phase or blast crisis after 3 to 6 months on therapy. Of four patients with a sex marker, the Ph- population was of donor origin in three and of host origin in one. Clonal cytogenetic abnormalities other than Ph were present in 13 patients and did not predict for lack of response to IFN. IFN is effective in suppressing the Ph clone in some patients who relapse with CML after allogeneic BMT and controls the blood counts in the majority. PMID- 1520871 TI - Growth hormone exerts hematopoietic growth-promoting effects in vivo and partially counteracts the myelosuppressive effects of azidothymidine. AB - Recombinant human growth hormone (rhGH) was administered to mice to determine its effect on hematopoiesis. BALB/c mice and mice with severe combined immune deficiency (SCID), which lack T cells and B cells, were administered intraperitoneal injections of rhGH for 7 days. Upon analysis, both strains of mice exhibited an increase in splenic and bone marrow hematopoietic progenitor cell content and cellularity, indicating that rhGH can act as a hematopoietic growth factor. C57BL/6 mice were then placed on azidothymidine (AZT). AZT is a reverse transcriptase inhibitor currently used as a treatment for acquired immune deficiency syndrome (AIDS), but which also produces significant myelotoxic effects. Treatment of mice with rhGH partially counteracted the myelosuppressive properties of AZT. Bone marrow cellularity, hematocrit values, white blood cell counts, and splenic hematopoietic progenitor cell content were all significantly increased if rhGH (20 micrograms injected intraperitoneally every other day) was concurrently administered with AZT. Administration of ovine GH (ovGH), which, unlike rhGH, has no effect on murine prolactin receptors, also prevented the erythroid-suppressive effects of AZT in mice, but had no significant effect on granulocyte counts. Thus, the effects of GH are mediated at least in part through GH receptors in vivo. Additionally, when mice were initially myelosuppressed by several weeks of AZT treatment, the subsequent administration of ovGH resulted in an increase in splenic hematopoietic progenitor cells. No significant pathologic effects were observed in mice receiving either repeated rhGH or ovGH injections. Thus, GH exerts significant direct hematopoietic growth-promoting effects in vivo and may be of potential clinical use to promote hematopoiesis in the face of myelotoxic therapy. PMID- 1520872 TI - Effect of human immunodeficiency virus-1 envelope glycoprotein on in vitro hematopoiesis of umbilical cord blood. AB - Although hypercellularity is a common bone marrow finding in patients with human immunodeficiency virus type 1 (HIV-1) infection, the effect of HIV-1 on the hematopoietic system, which has been investigated in in vitro studies, is still controversial. In this study, we have investigated the effects of HIV-1 envelope glycoprotein, gp160, on the differentiation of hematopoietic progenitor cells derived from cord blood. Culture of cord blood mononuclear cells with gp160 resulted in enhancement of the in vitro growth of myeloid hematopoietic progenitors. To investigate the mechanism of the enhancement, adherent cells, T cells, or CD34-bearing hematopoietic progenitors were isolated and cultivated with gp160 in a variety of culture conditions. We have shown that gp160 had no direct effect on highly purified hematopoietic progenitors but exerted its enhancing effect indirectly via T cells, by induction of a humoral colony stimulating factor(s). The activity of gp160 on T cells was abrogated by preincubation of gp160 with recombinant CD4 molecule and goat anti-gp120 antibody. These data provide evidence for a novel biological activity of HIV envelope glycoprotein, that of T-cell-mediated stimulation of myelopoiesis. Binding of gp160 with the cell surface CD4 molecule appears to be necessary for secretion of the colony-stimulating factor(s). PMID- 1520873 TI - Identification of lysosome-associated membrane protein-2 as an activation dependent platelet surface glycoprotein. AB - Platelets undergo biochemical and morphologic changes when stimulated that greatly alter their function and contribute to their role in thrombosis and hemostasis. We recently identified and cloned the cDNA for a platelet surface glycoprotein expressed on activated, not resting cells. We found that this protein, lysome-associated membrane protein-1 (LAMP-1), is an integral membrane protein of the lysosome that translocated to the surface membrane when platelets were stimulated by a strong agonist. We now show with immunofluorescence flow cytometry that LAMP-2, a lysosomal membrane protein that shares approximately 30% homology with LAMP-1, is also expressed preferentially on the surface of activated platelets. Equilibrium binding studies with 125I-anti-LAMP-2 IgG showed approximately 1,100 binding sites per thrombin-stimulated platelet and less than 50 per resting platelet. Sucrose gradient ultracentrifugation fractionation of resting platelet sonicates showed that LAMP-2 colocalized with LAMP-1 and with lysosomal enzymes, and not with thrombospondin or serotonin, which are markers of the two other platelet granule compartments, alpha-granules and dense granules. LAMP-2 surface expression was minimal in response to platelet stimulation by weak agonists such as epinephrine and ADP. These data show that LAMP-2, like LAMP-1, translocates from the lysosomal membrane compartment to the surface membrane when platelets are activated. Regulated surface expression of these heavily glycosylated proteins may play a role in the adhesive, prothrombotic phenotype of these cells. PMID- 1520874 TI - Partial deletion of an antithrombin III allele in a kindred with a type 1 deficiency. AB - This report details the precise mapping of a partially deleted human antithrombin III (AT-III) allele, found in a kindred with an inherited type 1 AT-III deficiency. Using truncated AT-III probes generated by polymerase chain reaction (PCR) amplification from a full-length AT-III cDNA, as well as other genomic probes specific for the 5' upstream region of the AT-III gene, we were able to characterize a partial deletion on an AT-III allele encompassing exons 1 and 2 of the AT-III gene, and a region 5' to the coding sequences. The absence of the 5' upstream region in the affected AT-III allele was confirmed directly by the PCR amplification of a 1.5-kb polymorphic fragment of genomic DNA samples from family members. The precise determination of the 5' breakpoint of the affected allele was made possible by two different approaches: (1) subcloning plus biotin capture PCR, or (2) inverse PCR. This allowed us to confirm the mapping of the deletion obtained by Southern analysis; to show that the 3' region of the mutant AT-III allele, including exons 3 to 7, was intact; and to sequence approximately 0.7 kb upstream to the breakpoint in the mutant allele. Furthermore, PCR amplification of the region of the breakpoint provided unique products detectable only in affected members of this kindred. The breakpoint in the partially deleted allele is 480 bp upstream from the 5' boundary of exon 3. No significant homology was found between the 0.7-kb sequence upstream to the breakpoint of the mutant allele and known human sequences. PMID- 1520875 TI - Heparin enhances active site-dependent binding of tissue-type plasminogen activator to endothelial cells. AB - Human umbilical vein endothelial cells (HUVEC) in culture express two classes of binding sites for tissue-type plasminogen activator (t-PA). The high-affinity binding site has been identified as PA inhibitor type 1 (PAI-1), which binds to the catalytic portion of the molecule, while the second site binds t-PA through an active-site independent domain. Because recombinant t-PA (rt-PA) is often administered concomitantly with heparin, we investigated the effects of heparin on rt-PA binding to HUVEC. Preincubation of HUVEC with heparin at 4 degrees C increased the binding of radiolabeled rt-PA in a time- and dose-dependent manner. One-half maximal increase in binding was observed within 10 minutes of heparin addition. When HUVEC were preincubated with optimal concentrations (5 U/mL) of heparin for 4 hours at 4 degrees C, a 2.5- +/- 0.2-fold increase in specific binding was observed (mean +/- SEM, n = 12, P less than .01). Other highly sulfated glycosaminoglycans and fucoidan (a sulfated polymer of fucose) stimulated rt-PA binding as well, whereas glycosaminoglycans with lower sulfate content than heparin did not. Several results suggested that heparin increased the binding of rt-PA to "cell-associated" PAI-1. First, only active-site dependent binding was enhanced by heparin, whereas binding of active-site blocked rt-PA was not affected. Second, extracts from HUVEC preincubated with heparin contained increased amounts of rt-PA-PAI-1 complexes as shown by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Third, antibodies to PAI-1 blocked the increased binding entirely. HUVEC preincubated with heparin also bound increased amounts of enzymatically active radiolabeled urokinase-type PAs. However, HUVEC preincubated with heparin did not express increased amounts of immunoreactive PAI-1. Therefore, heparin, at therapeutic concentrations, may enhance or stabilize the association of PAs with endothelial cell-associated PAI 1. PMID- 1520876 TI - Human eosinophils synthesize and secrete interleukin-6, in vitro. AB - Using the technique of in situ hybridization, we have shown that resting, unstimulated, human peripheral blood eosinophils, obtained from subjects with greater than 8% eosinophilia, transcribe and translate messenger RNA (mRNA) for interleukin-6 (IL-6). After incubation for 24 hours in culture medium alone, approximately 19% of eosinophils were positive for IL-6 mRNA. This may be a reflection of their in vivo activation, but also may suggest that the gene for this cytokine is constitutively expressed in eosinophils. After stimulation with interferon gamma (IFN gamma) (500 U/mL), the percentage of IL-6-mRNA+ cells increased to 51.3%. This was accompanied by an enhancement of intensity of the hybridization signals. The specificity of the IL-6 probe and the hybridization signals was confirmed by the use of an IL-6 sense probe and RNase pretreatment of cell preparations. Evidence for the translation of IL-6 mRNA was obtained by immunocytochemical staining. Normal and activated eosinophils gave IL-6-specific immunoreactivity with a polyclonal antihuman IL-6 antibody. A higher percentage of positive cells was detected among activated eosinophils than those treated with medium alone. Using a specific immunoenzymetric assay, we detected 190.15 +/ 18.1 and 403.32 +/- 213.6 pg/mL of IL-6 in supernatants of unstimulated and IFN gamma-treated (24 and 48 hours) eosinophils, respectively. These data indicate that eosinophils are an important cellular source of IL-6. PMID- 1520878 TI - Human lymphotropic retroviruses associated with mycosis fungoides: evidence that human T-cell lymphotropic virus type II (HTLV-II) as well as HTLV-I may play a role in the disease. AB - The human T-cell lymphotropic virus type I (HTLV-I) is causally associated with adult T-cell leukemia, but its role in mycosis fungoides (MF) has remained enigmatic. The virus is suspect because a small percentage of patients with MF have antibodies to it, the cells of others harbor deleted HTLV-I proviral sequences, and particles resembling HTLV-I emerge in cultured blood lymphocytes obtained from most patients. An alternative possibility is that disparate lymphotropic retroviruses may infect or affect a population of epidermotropic lymphocytes, leading to the same outcome, ie, MF. In studies designed to identify the particles detected in lymphocyte cultures of nine patients with a diagnosis of skin involvement characteristic of MF, this concept has gained support. While the cells of four patients provided evidence of HTLV-I infection, molecular hybridization with HTLV-II-specific pol probes showed HTLV-II in the cells of another patient. The 103-bp fragment amplified by the HTLV-II-specific probe was sequenced and proved to have greater than 90% homology with the same fragment amplified from cells known to be infected with HTLV-II. A role for HTLV-II in MF has not been suggested heretofore. Therefore, HTLV-I, HTLV-II, and their incomplete forms may be found in cells of MF patients, suggesting new theories regarding the pathogenesis of this disease. PMID- 1520877 TI - Monoclonal anti-idiotype antibody therapy of B-cell lymphoma: the addition of a short course of chemotherapy does not interfere with the antitumor effect nor prevent the emergence of idiotype-negative variant cells. AB - The Ig idiotype of B-cell lymphoma can be used as a tumor-specific target. Prior trials with monoclonal anti-idiotype antibodies alone and combined with alpha interferon have shown significant antitumor activity. In some patients, idiotype negative tumors emerged after treatment. In this trial, patients with relapsed non-Hodgkin's lymphoma were treated with two identical courses of monoclonal anti idiotype anti-body therapy. Concurrent with the second course, at a time when idiotype-negative cells were suspected to be proliferating, a pulse dose of chlorambucil was administered. Tumor biopsies obtained before the first and second courses of treatment and at relapse were analyzed for idiotype expression and proliferation. Thirteen patients received 24 courses of antibody with minimal toxicity. Eleven had tumor regression, with 1 complete remission, 8 partial remissions, and 2 minor remissions, with freedom from progression lasting a median of 7 months in responding patients. Idiotype-negative tumor cells appeared in some relapse specimens despite the use of chlorambucil. In retrospect, this was not surprising because there was no increase in the proliferative rate of these tumors at the time the drug was used. Anti-idiotype antibodies continue to demonstrate antitumor activity against B-cell lymphoma with minimal toxicity. The mechanism of the effect is presumed to involve both direct antiproliferative effects of the antibody on the tumor cells as well as indirect, more long-lasting effects on the host. The addition of a mild chemotherapeutic agent in the dose and schedule used here to the second cycle of antibody therapy did not interfere with the antitumor effect, nor did it decrease the emergence of idiotype-negative cells. PMID- 1520879 TI - K562 cells produce an anti-inflammatory factor that inhibits neutrophil functions in vivo. AB - We have previously reported that K562, a chronic myelogenous leukemia cell line, releases a low molecular weight factor (6 to 8 Kd) that inhibits human polymorphonuclear neutrophil (PMN) adherence and adherence-related functions tested in vitro. We now report that this factor, which we have named K562 inhibitory factor (K562-IF), has potent anti-inflammatory activity in mice, associated with an inhibition of PMN functions. Its in vitro actions were less marked with mouse PMN than with human PMN. They included (1) an inhibition of both nonstimulated locomotion and locomotion induced by FMLP or serum; (2) an inhibition of the chemiluminescence induced by opsonized zymosan, but not that induced by phorbol myristate acetate or FMLP; (3) an inhibition of the degranulation stimulated by opsonized zymosan, as reflected by lactoferrin and lysozyme release; and (4) a decrease in arachidonic acid release and leukotriene B4 production by A23187-stimulated PMN. The in vivo actions of K562-IF after intraperitoneal injection included (1) an inhibition of subcutaneous PMN accumulation at the site of injection of opsonized zymosan (PMN accumulated neither outside the vessels nor intravascularly, as shown by means of histochemistry); (2) an inhibition of neutrophil accumulation in the peritoneum of mice having received sodium caseinate or opsonized zymosan intraperitoneally; and (3) lysozyme concentration in neutrophils having reached the peritoneum after opsonized zymosan treatment equal to that in blood, suggesting diminished release. PMN influx and degranulation in the peritoneum were reduced by 50% after 3 hours of treatment with 1 microgram of K562-IF (equivalent to the effect of 120 micrograms of prednisolone). Taken together, these results show that K562-IF is a potent anti-inflammatory agent that acts by inhibiting PMN functions. PMID- 1520880 TI - Splice site mutations are a common cause of X-linked chronic granulomatous disease. AB - Chronic granulomatous disease (CGD) is characterized by the absence of a respiratory burst in activated phagocytes. Defects in at least four different genes lead to CGD. Patients with the X-linked form of CGD have mutations in the gene for the beta-subunit of cytochrome b558 (gp91-phox). We studied the molecular defect in four patients with X-linked CGD. In a fifth family, we studied the mother of a patient with X-linked CGD who had died before our investigations. Gp91-phox messenger RNA (mRNA) was reverse transcribed into cDNA and the coding region was amplified by polymerase chain reaction into three fragments. Sequence analysis showed the absence of the exon 7, 5, 3, and 2 sequences in patients 1, 2, 3, and 4, respectively. In carrier 5, we found both normal cDNA and cDNA that lacked 57 3'-nucleotides of exon 6. We analyzed the splice sites of the flanking introns of the missing exons. In patients 1, 2, and 3, we found single nucleotide substitutions within the first five positions of the down-stream 5' donor splice sites. In patient 4, a similar substitution was found at position -1 of the 3' acceptor splice site of intron 1. In carrier 5, no mutation was found in the exon 6-intron 6 boundary sequence. Instead, a single substitution was observed in exon 6 (C----A at nucleotide 633) that created a new donor splice site. Apparently, mRNA splicing occurs preferentially at this newly created splice site. We conclude that the absence of the exon sequences in the gp91-phox mRNA of these patients is due to splicing errors. Of 30 European X linked CGD patients studied by us so far, five appear to be caused by mutations that affect correct mRNA splicing. Thus, such mutations appear to be a common cause of X-linked CGD. PMID- 1520881 TI - Rapid detection of Spanish (delta beta)zero-thalassemia deletion by polymerase chain reaction. AB - delta beta-Thalassemia and hereditary persistence of fetal hemoglobin (HPFH) are inherited disorders characterized by the persistent synthesis of fetal hemoglobin (HbF) during adult life. The Spanish type of delta beta-thalassemia is a mild thalassemic condition due to a large deletion starting at the Alu I repeat between the A gamma and delta-globin genes immediately 3' to the RIH probe and extending 11 and 17 kb downstream of the 3' endpoints of HPFH 1 and HPFH 2, respectively. Using probes from the Spanish (delta beta)zero-thalassemic DNA, the 3' breakpoint region has been mapped to a point approximately 8.5 to 9.0 kb downstream from that of HPFH type 1 and, as we know the restriction sites 3' to this breakpoint, the presence of the deletion can be identified with the polymerase chain reaction (PCR). In the present study, a PCR method using three specific oligonucleotides has been developed for the identification of the Spanish (delta beta)zero-thalassemia in 100 patients with delta beta-thalassemia (99 heterozygotes with mild anemia, decreased mean corpuscular volume, and 5% to 15% HbF, and one homozygote with 100% HbF and thalassemia intermedia phenotype). We conclude that the finding of the Spanish type of (delta beta)zero-thalassemia in all the patients studied here suggests Spain as the most probable origin of this thalassemic phenotype. Moreover, the amplification of the fragment encompassing the deletion junction and normal sequence is useful for the rapid molecular detection of Spanish (delta beta)zero-thalassemia. PMID- 1520882 TI - Developmental switching of messenger RNA expression from the human alpha-globin cluster: fetal/adult pattern of theta-globin gene expression. AB - The alpha-globin gene cluster contains four functional globin genes, zeta, alpha 2, alpha 1, and theta. The developmental regulation of the embryonic zeta and fetal/adult alpha 2- and alpha 1-globin genes is well characterized at the level of protein synthesis. The developmental pattern of the theta-globin gene is not well characterized due to the inability to detect its encoded protein. Direct analysis of the globin switching at the steady-state messenger RNA (mRNA) level has been hampered by the difficulty in obtaining quantities of embryonic and early fetal mRNA sufficient for analysis. We analyzed the relative levels of the steady-state zeta-, alpha-, and theta-globin mRNAs in yolk sac in 5-, 6-, 7-, and 8-week postconception embryonic liver, and in cord and adult blood reticulocytes. We show that the switch in the alpha-globin gene cluster from the embryonic to fetal/adult pattern of expression begins at 5 to 6 weeks of gestation. Both the theta- and alpha-globin genes show similar patterns of developmental control that are reciprocal to zeta. alpha-globin RNA is barely detectable or undetectable at 5 weeks, and increases in the 6- to 8-week period, while theta-globin mRNA shows a parallel increase at 5 to 8 weeks postconception and is expressed in cord blood and adult reticulocytes. These data show that the theta-globin gene represents a fetal/adult gene, albeit expressed at a low level. PMID- 1520883 TI - Band 3 Memphis: a widespread polymorphism with abnormal electrophoretic mobility of erythrocyte band 3 protein caused by substitution AAG----GAG (Lys----Glu) in codon 56. AB - Band 3 Memphis (b3M) is a variant of the erythrocyte band 3 protein detected in individuals of virtually all ethnic groups and characterized by a reduced mobility of proteolytic fragments derived from the N-terminus of the cytoplasmic domain of band 3 (cdb3). We have sequenced band 3 cDNA corresponding to cdb3 in 12 heterozygotes for the b3M polymorphism including one white, one black, one Chinese, one Philippino, one Malay, and seven Melanesian subjects. In all individuals, we found a single-base substitution in codon 56 of one band 3 allele changing lysine to glutamic acid (AAG----GAG) which, in some of them, was linked with an additional mutation in cdb3. Since the change of codon 56 from AAG to GAG was the only mutation in the studied individuals found within the cDNA segment coding for the abnormally migrating fragment of cdb3, we conclude that it represents the underlying molecular basis of the b3M polymorphism. We further support this conclusion by showing that electrophoresis in the presence of 4 mol/L urea abolished the difference in migration between proteolytic products of b3M and normal band 3, and that a fusion protein prepared from cDNA coding for the b3M allele again exhibits reduced electrophoretic mobility compared with the normal fusion protein. Finally, since most of the previously cloned mouse, rat, and chicken band 3 and band 3-related proteins contain glutamic acid in the position corresponding to amino acid 56 in the human band 3, we propose that the Memphis variant is the evolutionarily older form of band 3. PMID- 1520884 TI - Relevance of pretransfusion incubation of platelets at 37 degrees C. AB - The effect of pretransfusion incubation of platelets at 37 degrees C was assessed because of the controversial reports about its relevance. A dual-label technique (111indium and 114mindium) was applied in 10 healthy subjects receiving warmed and unwarmed autologous platelets simultaneously. Fresh platelet concentrates were infused into five subjects, whereas the other five subjects received stored platelet concentrates. The mean platelet volume decreased in all platelet concentrates during incubation, reflecting the restoration of the discoid shape of the platelets. The mean decrease was 0.35 fL (P = .003). However, the initial recovery and the mean platelet life-span were not improved by this procedure. It was concluded that there is no evidence that brief warming of platelets has any beneficial effect on platelet viability in healthy volunteers. PMID- 1520885 TI - Bone marrow transplantation in adult thalassemia. AB - Early trials of allogeneic marrow transplantation for homozygous thalassemia were disappointing in patients older than 16, with four of six patients dying early of graft-versus-host disease-related complications, one patient dying at 9 months of infection due to graft failure, and one dying at 6 years of recurrent thalassemia. Three classes of risk could be identified in analyses of results of transplantation in younger patients using the criteria of degree of hepatomegaly, the presence or absence of portal fibrosis, and a history of adequate or inadequate chelation therapy. Patients for whom all three criteria were adverse constituted a very high risk group (class 3) for marrow transplantation. On the basis of these analyses, a conditioning regimen was designed that yielded superior results for class 3 patients under 17 years of age. Most patients older than 16 years presenting for transplantation have disease characteristics that place them in class 3 and, because of the improved results with the new class 3 regimen in younger patients, a study was designed to treat patients older than 16 years using treatment regimens assigned on the basis of disease class. Twenty patients were treated using this protocol and, with a minimum follow-up of 9 months, there have been three early deaths, one patient has recurrent thalassemia, and 16 patients are alive disease-free. The actuarial probabilities of survival, disease-free survival, and rejection are 0.85, 0.80, and 0.05, respectively, with a survival plateau extending from 6 months to 3 years. Marrow transplantation is a reasonable option for adults with progressive thalassemia who have suitable donors. PMID- 1520886 TI - Specific marrow ablation before marrow transplantation using an aminophosphonic acid conjugate 166Ho-EDTMP. AB - 166Holmium ethylenediaminetetramethylene phosphonic acid (166Ho-EDTMP) is a short lived beta-emitting radionuclide complexed to an aminophosphonate ligand that we have investigated in a canine model as a potential agent for specific marrow ablation before marrow transplantation. After intravenous injections, 166Ho-EDTMP distributed principally to bone and after 24 hours the concentrations of 166Ho EDTMP in bone were more than 200-fold higher than in any other organ. Increasing dosages of 166Ho-EDTMP led to increasingly prolonged and severe myelosuppression, but myeloablation was not achieved. Histologic examination of recovering animals suggested that the spleen may have acted as a reservoir for circulatory hematopoietic precursors. Four splenectomized animals administered 20 to 30 mCi/kg 166Ho-EDTMP without marrow transplantation died with marrow aplasia, while four splenectomized animals administered similar dosages of 166Ho-EDTMP followed by autologous transplantation recovered. The dose-limiting toxicity of 166Ho EDTMP appeared to be marrow stromal damage resulting in myelofibrosis, which was reversible. These results suggest that 166Ho-EDTMP can be used to specifically ablate marrow function before marrow transplantation. PMID- 1520887 TI - Collection of umbilical cord blood for transplantation. PMID- 1520888 TI - Collection of umbilical cord blood for transplantation. PMID- 1520889 TI - Hereditary stomatocytosis and Rh-deficient patients exhibit distinct molecular defects. PMID- 1520890 TI - Safe and successful clinical use of the defibrinogenating agent ancrod. PMID- 1520891 TI - Clonal instability in early B-lineage acute lymphoblastic leukemia. PMID- 1520892 TI - The social epidemiology of falls among community-dwelling elderly: guidelines for prevention. AB - Social epidemiology offers a conceptual model that organizes the risk factors for falls into demographic, medical and psychosocial host factors, environmental factors and the agent in falls. Once identified in such a manner it is possible to differentiate between those factors which are or are not amenable to change or treatment, thus suggesting methods of fall prevention. Fall prevention strategies are feasible before a fall, at the time of a fall, and following an injurious fall, corresponding to primary, secondary, and tertiary prevention. At each level of prevention, prevention strategies are described, and together they constitute a complete fall prevention programme for community-dwelling elderly. A review of those strategies that have been evaluated shows that their efficacy in reducing the incidence of falls and their adverse complications is generally limited. Thus, further evaluation research is needed in order to incorporate the most effective fall prevention programmes into standard community care for the elderly. PMID- 1520893 TI - A cross-cultural assessment of perceived health problems in the elderly. AB - To study cross-cultural differences in perceived health problems in the elderly the Nottingham Health Profile (NHP) developed by Hunt et al. was administered to subjects from the People's Republic of China and Australia. The Australian stratum was further categorized according to cardiovascular status. Analyses of covariance (with age as the covariate) on each of the six subscales of the NHP yielded significant differences for 'Energy', 'Pain', 'Emotional reactions', 'Social isolation' and 'Physical mobility'. No differences were found for the 'Sleep' subscale. Through comparisons between the mean scores for the four strata and from normative data it is concluded that it is likely that the NHP is 'culture free' on the dimensions 'Energy', 'Pain', 'Emotional reactions', 'Social isolation' and 'Physical mobility'. PMID- 1520894 TI - Perceptual impairment after stroke: improvements during the first 3 months. AB - The aim of the study was to assess changes in perceptual abilities during the first 3 months after stroke using a prospective observational design. The sample was from a hospital with a catchment population of 205,000. Seventy persons aged 60+ admitted with non-lacunar stroke were given the Rivermead Perceptual Assessment Battery, 2 weeks after stroke. Three months post-stroke subjects were reassessed on subtests they had initially failed. The improvements in performance on all 16 subtests of the RPAB were significant, and large in relationship to the maximal possible improvement had all subjects achieved perfect scores on follow up. Performance on line bisection and line cancellation also improved significantly. In spite of these improvements 64% of subjects still had perceptual impairment as defined by an RPAB score of 0-12 at 3 months post stroke. It is concluded that perceptual abilities improved greatly during the first 3 months after non-lacunar stroke but nevertheless perceptual impairments remain common at 3-month follow-up. PMID- 1520895 TI - Identifying safe versus unsafe drivers following brain impairment: the Coorabel Programme. AB - The Coorabel Driver Assessment and Training Programme commenced in January 1988, with the aim of providing assessments of the ability of people with a disability to resume or commence driving. This programme incorporates assessments by a medical practitioner, a neuropsychologist, an occupational therapist and a driving instructor, conducted both off and on the road. The first 129 consecutive referrals were reviewed. Non-brain-impaired clients demonstrated a lower failure rate relative to brain-impaired clients. Diagnosis was not found to have predictive value within the brain-impaired clients, and there was no statistical difference in failure rates between left and right hemispheric strokes. Whilst only six cases failed the medical assessment, in 47 cases the medical practitioner was unable to make a final decision regarding driver competence. Neuropsychological and on-road assessments resulted in definitive decisions for 39 of these 47 cases. Twenty cases passed the medical assessment but subsequently failed the neuropsychological or on-road assessment. Only three cases passed at neuropsychological assessment subsequently failed on-road testing. It is suggested that multidisciplinary assessment of driver competence, inclusive of on road testing, is essential, as medical guidelines alone are insufficient to predict driver fitness. PMID- 1520896 TI - The diversity of speech and language therapy services for aphasic adults in the United Kingdom. AB - Data on aphasia management were collected by questionnaires to UK speech and language therapists. Returns representing over 90% of health districts were obtained. Variation amongst districts is evident in levels of staffing for the adult neurological case load, and in speed of response to referral, frequency and types of treatment available, and in other forms of support for patients and carers. Although individual therapists or districts are able to adhere to some of the professional recommendations for a 'quality' service, few are able to provide this high level of care in all aspects of aphasia management. PMID- 1520897 TI - Rehabilitation after a letter-bomb attack causing bilateral hand loss and other injuries: case report. AB - The rehabilitation of patients after terrorist attacks has received scant attention in the literature. A case is reported of a patient injured in a letter bomb explosion; his injuries were bilateral hand loss, loss of one eye, and perforated ear-drums. The successful rehabilitation of this patient to normal work in 8 months is described. A rehabilitation plan for management of similar patients is given. PMID- 1520898 TI - Cyclosporin reduces renal prostanoid excretion in type 1 diabetic patients. AB - Prostacyclin and thromboxane A2 are important regulators of kidney blood flow. To examine whether changes in their metabolism could be involved in the nephrotoxicity of cyclosporin, we determined urinary excretion of 6-keto PGF1a and dinor-6-keto PGF1a (prostacyclin metabolites) and dinor-TxB2 (thromboxane metabolite) in five newly diagnosed type 1 diabetic patients during and after stopping cyclosporin therapy. In the resting state, cyclosporin had no effect on prostanoid excretion. In response to exercise, urinary excretion of 6-keto PGF1a was reduced by 50% (P less than 0.02), dinor-6-keto PGF1a by 15% (P less than 0.05) and dinor-TxB2 by 45% (P less than 0.02), while albumin excretion increased 4.5-fold (P less than 0.05) during cyclosporin therapy. Simultaneously, there was a rise in serum creatinine concentration, and renal biopsy specimens obtained from three patients showed periglomerular and interstitial fibrosis and tubular atrophy. After the discontinuation of cyclosporin therapy, serum creatinine concentrations returned to normal, histological changes improved and there was an associated rise in urinary prostanoid excretion. These data suggest that a reduction in renal prostanoid synthesis by cyclosporin may diminish renal blood flow and function, and lead to histological changes in the kidney. PMID- 1520899 TI - Exercise is not associated with better diabetes control in type 1 and type 2 diabetic subjects. AB - In the clinical setting, the impact of educational efforts on the amount of regular exercise and its effects on diabetes control are unclear. Fifty type 1 diabetic, 50 type 2 diabetic and 70 non-diabetic subjects were evaluated using a questionnaire for type, duration and intensity of exercise to assess weekly energy expenditure. Diabetic subjects did not exercise more than controls: 36% of the type 1, 46% of the type 2 and 46% of the control subjects admitted no physical activity, and those exercising regularly had similar energy expenditure: 1808 +/- 320, 2722 +/- 617, 2523 +/- 304 (mean +/- SEM) kcal/week respectively (P = NS). There was no correlation between the degree of activity and HbA1c levels, or hypoglycaemic events. HbA1c levels were less than 6,8% in 31% of nonactive patients versus 21% of active patients (P = NS). A negative correlation was found between physical activity and daily insulin usage (r = 0.27, P less than 0.05), but differences between patients averaged only 4IU/1000 kcal energy expenditure/day. We conclude that patients' attitude towards exercise was not improved by our educational methods and that physical exercise was not necessarily associated with good blood glucose control. PMID- 1520901 TI - A simple clinical approach to discriminate between "true" and "pseudo" secondary failure to oral hypoglycaemic agents. AB - To discriminate between true secondary failure (TF) and pseudo-secondary failure (PF) to oral hypoglycaemic agents, we studied 34 non-obese non-insulin-dependent diabetic patients who were being treated with these drugs. Nine were in good control (GC) with oral treatment, while 25 showed apparent SF. During a controlled hospital diet, fasting blood glucose remained persistently high in 15 of these patients (TF), while in the other 10 patients it clearly improved (PF). Fasting plasma glucose (FPG) and HbA1c were higher and body mass index (BMI) was lower in TF patients than in PF patients (P less than 0.01). C-peptide concentrations differed significantly among the three groups both in the fasting state (TF 0.25 +/- 0.02 nmol/l, PF 0.70 +/- 0.03 nmol/l, GC 0.74 +/- 0.03 nmol/l; P less than 0.0001) and 6 min after glucagon injection (TF 0.50 +/- 0.04 nmol/l, PF 1.02 +/- 0.06 nmol/l, GC 1.14 +/- 0.07 nmol/l; P less than 0.0001). C-peptide and plasma insulin curves obtained after a standard mixed meal also showed significant differences (P less than 0.001). In particular, there was a statistically significant difference between GC and PF versus TF (P less than 0.05), while there was no statistical difference between PF and GC. We conclude that some patients with apparent SF can improve their metabolic control if they strictly adhere to a correct diet (PF); a single measurement of basal C-peptide concentration or examination of the C-peptide and insulin responses to a meal are useful indicators for distinguishing patients with PF from those with TF to oral hypoglycaemic agents.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1520900 TI - Long-term fat-feeding-induced insulin resistance in normal NMRI mice: postreceptor changes of liver, muscle and adipose tissue metabolism resembling those of type 2 diabetes. AB - Postreceptor insulin resistance was studied in liver, muscle and adipose tissue from NMRI mice of both sexes made diabetic by long-term fat-feeding. Intravenous glucose tolerance tests showed a combination of impaired glucose tolerance and increased plasma insulin concentrations consistent with insulin resistance and reduced peripheral and hepatic uptake of glucose. In the morning, the fat-fed mice were normoinsulinaemic and hyperglycaemic. Liver glucokinase activity and glycogen content were reduced whereas lactate dehydrogenase activity was enhanced. Fatty acid synthase activity was decreased but glucose 6-phosphate dehydrogenase and the rate limiting enzyme in fatty acid synthesis, acetyl CoA carboxylase, were both unaffected. In muscle, the proportion of glycogen synthase in the active I-form was decreased. Total glycogen synthase activity was not affected. In isolated adipocytes, basal and insulin-stimulated glucose oxidation, as well as basal and insulin-stimulated lipogenesis from glucose were all severely inhibited, oxidation more so than lipogenesis. It is concluded that insulin resistance and postreceptor metabolic disorders in liver, muscle and adipose tissue from mice made diabetic by long-term fat-feeding are very similar to those demonstrated in human type 2 diabetics and may be studied in more detail and with more ease in this particular animal model. PMID- 1520902 TI - Impaired cutaneous reactive hyperaemia during hypoglycaemia in young insulin dependent diabetic patients and healthy controls. AB - The aim of the present study was to compare the cutaneous postischaemic hyperaemic response in young insulin-dependent diabetic patients and healthy subjects during normoglycaemia, acute insulin-induced hypoglycaemia and in the posthypoglycaemic state. After a night of normoglycaemia the cutaneous postischaemic hyperaemic response in the forearm skin, measured by the transcutaneous PO2 method, was the same in both groups. A reduction of the maximal postischaemic vasodilatory response was observed in diabetic patients from 2.4 +/- 0.3 to 2.0 +/- 0.2 kPa (P less than 0.05) and in control subjects from 2.7 +/- 0.3 to 1.8 +/- 0.2 kPa (P less than 0.02) during insulin-induced hypoglycaemia (plasma glucose less than 2 mmol/l). Complete recovery of the vasodilatory response occurred in subjects in the posthypoglycaemic state. We conclude that hypoglycaemia induced a transient reduction of the vasodilatory response, which was rapidly reversed after glucose counter-regulation, in both diabetic patients and healthy controls. Thus, the prevailing blood glucose concentration must be taken into account when the postischaemic vasodilatory response is investigated in diabetic patients. PMID- 1520903 TI - Comparison of the metabolic effects of mixed meal and standard oral glucose tolerance test on glucose, insulin and C-peptide response in healthy, impaired glucose tolerance, mild and severe non-insulin-dependent diabetic subjects. AB - Dietary constituents other than glucose can influence insulin secretion in non insulin-dependent diabetes mellitus and administration of a standard mixed meal has been proposed as a more physiological test in regard to human diet for evaluating the patient both at the time of diagnosis and during follow-up. This study was carried out to compare the effects of a standard meal and the oral glucose tolerance test on glucose, insulin and C-peptide plasma levels in four groups of subjects: healthy controls, subjects with impaired glucose tolerance, patients with mild non-insulin-dependent diabetes, and non-insulin-dependent diabetic patients with secondary failure to oral agents. Plasma glucose values were significantly higher after the oral glucose tolerance test than after the mixed meal in all four groups of subjects. Plasma insulin and C-peptide values were similar during the two tests in all groups of subjects except in non-insulin dependent diabetics with secondary failure (flattened curves). Insulin and C peptide responses per unit rise in blood glucose were significantly higher after the oral glucose tolerance test than after the mixed meal both in mild non insulin-dependent diabetics (P less than 0.05 and P less than 0.05) and in non insulin-dependent diabetics in secondary failure (P less than 0.01 and P less than 0.05). There was significant correlation between oral glucose tolerance test and mixed meal glucose incremental areas (r = 0.511, P less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1520904 TI - Effects of hyperglycaemia on visual evoked potentials in insulin-dependent diabetic patients. AB - Multimodality evoked potentials frequently reveal subclinical involvement of the central nervous system in patients with insulin-dependent diabetes mellitus. We devised this study to evaluate the possible effects of acute hyperglycaemia on visual evoked potential (VEP) parameters in type 1 diabetic patients. A hyperglycaemic clamp (250 mg/dl for 180 min) was performed in ten patients. Monocular pattern reversal VEPs (check size 15', contrast 50%) were recorded before, and every 30 min after the start of the clamp. Basal VEP latencies and amplitudes were normal bilaterally in nine patients. No significant changes in pattern reversal and flash VEP parameters were observed after the induction or during the clamp period. None of the neurophysiological parameters evaluated during the test was related to the duration of the disease, the basal VEP latency or amplitude or the presence of retinopathy. Our data suggest that the neurophysiological abnormalities detected in insulin-dependent diabetic patients are due to structural involvement of the central nervous pathways and not to functional damage induced by acute short-term hyperglycaemia. PMID- 1520905 TI - Familial insulinoma: description of two cases. AB - We describe cases of isolated functioning insulinoma occurring in two members of the same family (father and daughter). The father had a first encapsulated insulinoma diagnosed at 14 years of age and at the age of 33 years he was operated on for a second insulinoma infiltrating the exocrine pancreas with lymph node metastases. The daughter was operated on for an encapsulated insulinoma in the tail of the pancreas when she was 6 years old. No clinical and laboratory signs of other endocrine disturbances have so far been detected in either care or in any other members of the family. Our report suggests the possibility of multiple familial insulinoma, although this is an extremely rare condition. Our data also indicate that insulinomas, even if well controlled by medical treatment, should always be removed by surgery because malignancy cannot be excluded with certainty. Moreover, patients should be closely followed up, as recurrence may develop up to 15 years after surgery. PMID- 1520906 TI - Alginate coating of islets of Langerhans: in vitro studies on a new method for microencapsulation for immuno-isolated transplantation. AB - Immuno-isolated transplantation offers the attractive prospect of being able to transplant xenogeneic islets without immunosuppression. This study introduces a completely new method of coating single islets using a homogeneous alginate membrane approximately 10 microns thick. During glucose challenge (perifusion and static incubation) encapsulated islets show the same pattern and quantity of insulin release as non-encapsulated controls. This encapsulation method markedly reduces the amount of transplanted material by reducing the size of the capsule. It is suggested that encapsulated islets may be transplanted into sites such as the renal capsule or omentum or even by intraportal injection into the liver. PMID- 1520907 TI - Relationship between plasma leucine concentration and clearance in normal and type 1 diabetic subjects. AB - In a series of studies in normal and type 1 diabetic subjects, we analysed the relationship between isotope-calculated leucine clearance and plasma leucine concentration. All studies were performed under euglycaemic conditions. Plasma leucine concentrations were either experimentally decreased by means of insulin infusion, or increased by means of exogenous amino acid infusion in the presence of hyperinsulinaemia. Leucine clearance rates were compared in normal and diabetic subjects at similar plasma insulin levels. The effect of hyperinsulinaemia was examined by measuring clearance rates in normal subjects at comparable leucine levels but different insulin concentrations. Our data show that leucine clearance is inversely related to leucine concentration, and that it is not independently stimulated by hyperinsulinaemia. Type 1 diabetes is not associated with decreased leucine clearance. A general equation relating leucine concentration and clearance is proposed. These data support the view that peripheral leucine utilization is not decreased in type 1 diabetes mellitus. PMID- 1520908 TI - Interleukin-3 in the treatment of myelodysplastic syndromes. AB - Patients with myelodysplastic syndromes frequently present with anemia, leukopenia and thrombocytopenia due to defective maturation of bone marrow cells. Clinical studies with hematopoietic growth factors, including interleukin-3 (IL 3), have been undertaken to evaluate the possibility to reverse cytopenia. In initial phase I/II trials, treatment with IL-3 has resulted in an increase of neutrophil counts in 59%, of platelet counts in 34%, and in reticulocyte counts in 25% of the patients. Adverse effects were rather mild but in individual patients a reversible decrease in platelet counts and in the number of blast cells in blood and bone marrow were observed. Further clinical trials should concentrate on the combination of an early acting cytokine like IL-3 and later acting hemopoietic growth factors like erythropoietin and granulocyte colony stimulating factor. PMID- 1520909 TI - Will a tumor metastasize? Quantitate, semi-quantitate or pseudo-quantitate? A brief review of the microscopic prediction of tumor metastasis. AB - This review examines ways in which histopathologists can attempt to predict whether a neoplasm will metastasize by microscopic examination of surgically removed samples of human neoplasms. These include qualitative description, semi quantitative analysis of differentiation and proliferation, or of the nature of the edge of the neoplasm, and quantitative analysis of mitotic counts. More recently measurement of DNA content, analysis of DNA turnover, measurement of proliferation antigens, measurement of nucleolar organizing areas, counting nucleoli, morphometry of nuclei and identification of genetic change have become possible. There is no test capable of uniform accurate prediction of prognosis. In certain types of neoplasms in individual sites useful prognostic information can be obtained either by rigorous semi-quantitative microscopic analysis or by quantitative microscopical analysis. There is still doubt as to whether newer quantitative techniques will perform uniformly better than older semi quantitative techniques. The simple subjective statement "high-grade malignancy, average malignancy, low malignancy" is better than elaborate non-reproducible pseudo-quantitation. PMID- 1520911 TI - Interleukin 6: presence and future. AB - This review article deals with the basic biological characteristics of the multifunctional cytokine interleukin-6 (IL-6) in man. Three central issues will be addressed more closely: the pathophysiological role of unbalanced IL-6 production in various disease states, the diagnostic usefulness of measurements of IL-6 in biological fluids, and the possible role of IL-6, IL-6 antagonists, and IL-6 derivatives as therapeutic tools in clinical medicine. PMID- 1520912 TI - The estimation of free light chains of immunoglobulins in biological fluids. AB - Methods for the estimation of the free light chains of immunoglobulins in serum, urine and cerebrospinal fluid are divided into two groups, electrophoretic and immunological, and the analytical performance of each method described. The problems associated with the accurate and precise determination of free light chains by the different methods are discussed and their complementary clinical roles emphasized. It is proposed that an International Reference Preparation for free light chains is established. PMID- 1520910 TI - The interleukin-2/interleukin-2 receptor system: structural, immunological, and clinical features. AB - Interleukin-2 (IL-2) has been the first and more extensively studied cytokine, in particular for its central role in the mechanisms of cell growth and differentiation. The function of IL-2 is mediated through specific receptors (IL 2R) present on the membrane of reacting cells. Using hybridoma and recombinant DNA technologies, both IL-2 and IL-2R have been biochemically characterized and purified and are available for in vitro and in vivo studies. The biological and clinical investigations on IL-2/IL-2R system have contributed to opening new avenues for the comprehension of phenomena that are critically important for biology, immunology and medicine. PMID- 1520913 TI - Detection of a transcriptional block in the first intron of the human c-myb gene. AB - The levels of expression of the murine c-myb gene, like those of several other proto-oncogenes, can be controlled by a block of transcriptional elongation within the first intron of the gene. We have performed run-off experiments with double- and single-stranded probes on the myelomonocytic cell line U937, and show that this mechanism of transcriptional arrest is true also for the human c-myb gene and takes place within the first intron. Furthermore, we have sequenced the entire first intron of the human c-myb gene, and discuss the sequence structure in relation to its putative ability to arrest RNA polymerase II and its high degree of homology with the equivalent murine intron. PMID- 1520914 TI - Demonstration of a possible link between high grade malignancy in dimethylbenz[a]anthracene-induced rat mammary carcinoma and increased urokinase plasminogen activator content. AB - Recent reports have suggested that tissue-type plasminogen activator activity is regulated by estrogen in 7,12-dimethylbenz[a]anthracene-induced rat mammary carcinoma type I cells but is not necessarily regulated by estrogen in type II mammary carcinoma cells. We have compared the biological features of these two types of mammary carcinoma cells and have found that, although there is no difference in estrogen receptor content between these two cell types, the plasminogen activator activity markedly differs. Tissue-type plasminogen activator activity is significantly higher in type I carcinoma than in type II carcinoma, urokinase-type activity is significantly higher in type II carcinoma than in type I carcinoma. When these two types were compared in terms of rate of tumor growth, type II carcinomas clearly showed more rapid growth than type I carcinomas. Survival studies showed significantly shorter survival of type II tumor-bearing rats compared with type I tumor-bearing rats. Furthermore, type II carcinomas contained a greater proportion of aneuploid cells than type I carcinomas. These results suggest that type II carcinoma cells, in which estrogen is unable to regulate tissue-type plasminogen activator activity, are considered to be of a higher grade of malignancy than type I carcinoma cells. PMID- 1520915 TI - Antithrombotic and thrombolytic activity of sulodexide in rats. AB - We evaluated the ability of sulodexide, an extracted glycosaminoglycan, to prevent thrombus formation and to reduce a stabilized thrombus in a rat venous thrombosis model (vena cava ligature). Injection of sulodexide 10 min before induction of venous stasis, prevented thrombus formation in a dose-dependent manner (median effective dose 0.55 mg/kg). When given to rats with 6-h-old thrombi, sulodexide caused a marked reduction in thrombus size which reached 70% after 2 h with the highest dose tested (2 mg/kg). The effect of sulodexide on established thrombi appears to be due, at least in part, to a fibrinolysis mediated mechanism, since it was significantly inhibited by epsilon-aminocaproic acid, a well-known antifibrinolytic drug. Treatment with sulodexide did not noticeably affect plasma levels of plasminogen activator and its specific inhibitor. We also showed that fluorescein-labelled sulodexide, when given to animals with 6-h-old thrombi, was present within the thrombi harvested 2 h later, but was then absent from blood. The fluorescence was mainly located in areas filled with amorphous material, that was identified as fibrin by staining with phosphotungstic acid-hematoxylin. No fluorescein-labelled material could be detected in rats treated with fluorescein alone. These findings indicate that, besides preventing venous thrombus formation, sulodexide is able to promote thrombus dissolution by a mechanism that is partly related to local fibrinolysis stimulation. PMID- 1520916 TI - Periodontology and restorative dentistry. PMID- 1520917 TI - Comparative means of dose reduction in dental radiography. AB - This review on dose reduction in dental radiography focuses on criteria for selecting the frequency and type of radiographs to be performed on patients. By making radiographs only when there is a reasonable probability of a finding that will influence patient care, patient exposure and other radiographic costs may be substantially reduced. Patient dose may also be reduced by half by changing from D-speed film to E-speed film for intraoral radiography and by more than half by changing from calcium tungstate intensifying screens to rare-earth intensifying screens for panoramic and cephalometric radiography. Using rectangular collimation for intraoral radiography will also further reduce patient exposure by about fourfold. Finally, the use of time-temperature processing will prevent overexposure of the patient and underprocessing of the radiographs; optimal radiographs will be provided. PMID- 1520918 TI - The use of lasers in periodontology. AB - Clinical lasers are of two types: "soft" and "hard" lasers. Soft lasers are claimed to aid healing and to reduce inflammation and pain. However, few rigorous studies are available to support their use. Surgical hard lasers can cut both hard and soft tissues, and newer varieties can transmit their energy via flexible fiberoptic cables. Many procedures can be performed without local analgesia, and because lasers sterilize as they cut, in spite of current controversies, they promise to find uses in all disciplines of dentistry, including periodontics. PMID- 1520920 TI - Surgical management of endodontically treated teeth. AB - Surgical endodontics has become an important treatment modality in modern dentistry. The evolution and development of this modality has suffered from decades of empiricism, as techniques, concepts, and root-end filling materials were advocated without supporting scientific evidence. The techniques and concepts of periodontal surgery and oral and maxillofacial surgery were long assumed to directly apply to endodontic surgery. Evidence now suggests that certain procedures adopted from other specialties are not indicated for surgical endodontics and, in fact, may be counterproductive. During the past year, the most important developments have emerged in the area of surgical wound healing as it relates to soft tissue management procedures. New techniques and concepts that enhance rapid wound healing and decrease untoward postsurgical sequelae have been proposed. PMID- 1520919 TI - Treatment of failing dental implants. AB - Recent studies show that the bacterial flora in adult periodontitis and peri implantitis are identical, but there could be a more pathogenic flora (gram negative bacteria, spirochetes) in the partially edentulous implant case than in the fully edentulous implant case. These data indicate a possible seeding mechanism from the natural tooth pocket to the implant crevice and may place the implant in the partially edentulous case more at risk. Also, understanding of the importance of loading in a progressive sense to prevent retrograde peri implantitis involving the dental implant has increased; the density of bone must be evaluated more fully to determine the time frame necessary to gain a compact bone capable of withstanding occlusal forces at the bone-implant interface. PMID- 1520921 TI - Dentin- and enamel-bonding agents. AB - The introduction of bonding agents in restorative dentistry has made it possible to adhere restorative materials to tooth structure. Since bonded restorations were introduced by Buonocore in 1955, extensive research has been conducted to develop systems that bond equally effectively to enamel and dentin. Researchers have identified a micromechanical retention mechanism for the attachment of hydrophobic resin restorative materials to both enamel and dentin that works if appropriate conditioning or priming steps are applied. At the dentin site, the modes of action of current adhesive systems converge to create a resin-dentin interdiffusion zone between the deep dentin structures and the filling material. To incorporate or remove the smear layer in this interdiffusion zone, different adhesion strategies are followed to obtain a resin-dentin bond. In the clinical situation, these modern dentin-bonding systems are more technique sensitive; the thickness of the interface, its elastic capacity, the polymerization efficiency and initiation of the bonding agent, and, finally, the application technique used for the restorative material play an important role in the final result. PMID- 1520922 TI - Bibliography of the current world literature. Prosthodontics. PMID- 1520924 TI - Bibliography of the current world literature. Endodontics. PMID- 1520923 TI - Composite-resin materials and techniques in dentistry. AB - Important features to consider when selecting composite resins are filler size and amount, radiopacity, and fluoride content. Submicron particles provide the best polishability, and heavily filled resins demonstrate better wear resistance. The radiopacity of the composite resin should slightly exceed that of enamel to allow visualization of the restoration and recurrent decay. Fluoride added to the matrix may arrest the progression of caries. Properly cured composite resins should not cause chronic pulpal irritation; however, infection of the cervical contraction gap resulting from poor bonding to root surfaces may cause pulpal irritation. Techniques to improve curing include incremental build-up, reflective matrices and wedges, and controlling the direction of light vectors. A surface sealant is highly recommended to reduce wear, especially in the posterior region. Porcelain veneers perform better clinically than do composite-resin veneers. Class I and II composite-resin restorations reinforce weakened tooth structure; however, problems with cervical leakage and wear prevent the recommendation of these materials for larger posterior restorations that involve occlusal contacts or that require bonding to root surfaces. PMID- 1520925 TI - Glass ionomer (polyalkenoate) cement restorations. AB - Glass ionomer cements are recognized for their properties of reliable adhesion to tooth structure and fluoride release. The introduction of light-cured base and liner glass ionomer cements has overcome some of the disadvantages of self-cured materials. During the review period, most papers deal with either fluoride release, microleakage, or adhesion. There were few clinical studies. PMID- 1520926 TI - Bleaching of vital and nonvital teeth. AB - Although tooth bleaching has been known to the dental profession for over 100 years, new knowledge is continually surfacing. This review discusses the 1990 to 1991 literature on two nonvital bleaching techniques (thermocatalytic and walking) and three classes of vital bleaching techniques (in-office; dentist prescribed, home-applied; and over-the-counter kits). The choice for nonvital bleaching is the walking bleach technique, with the use of sodium perborate alone having less potential for cervical resorption. The choices for vital bleaching techniques are either the dentist-prescribed, home-applied technique, the in office technique, or a combination of the two. Bonding should be delayed 2 weeks after bleaching. Microabrasion is a possible second choice for certain discolorations. These chosen bleaching techniques, when used in a professionally appropriate manner, seem as safe as other commonly used dental treatments. PMID- 1520927 TI - Amalgam in the restoration of posterior teeth. AB - The use of aesthetic restorative materials such as cast ceramic, porcelain, and composite resin for the restoration of posterior teeth has increased in recent years, but amalgam remains the most frequently used material. Although stories in the media recently renewed the debate over amalgam safety, amalgam has remained in the armamentarium of the average clinician in large part because of its long positive clinical history, beneficial physical properties, and forgiving handling characteristics. PMID- 1520928 TI - Changing paradigms in caries management. AB - Management of dental caries patients is taking on a new look. Caries is the clinical manifestation of an oral infection. The primary organisms involved are Streptococcus mutans. The infective nature of the disease has been well researched and reported. Treatment of this infection with antibacterial measures is becoming routine in developed countries. In the United States, the overall caries rate is decreasing. However, the distribution of caries is now skewed. Twenty percent of the population has 60% of the caries. These individuals have a significant level of infection or a major lack of resistance to the organisms and their by-products. Major strategies are being developed to control these infections and limit their recurrence. This review focuses on the developments in prevalence studies, diagnosis, and treatment of the caries infection. PMID- 1520929 TI - Comparative imaging of the temporomandibular joint. AB - During this annual review period, the literature reflected the great interest in magnetic resonance imaging as a diagnostic tool for assessing the various types of disk displacement and for postoperative imaging, due to its exceptional visualization of the normal and abnormal temporomandibular joint compared with other imaging modalities. None of the authors doubt the potential of magnetic resonance imaging and the interest shown in defining both the normal range of disk position and the pitfalls in the interpretation is a sound development. Arthrography still has its advantages and seems to be the only competitive imaging modality for the assessment of internal derangement; it also has been shown to detect mediolateral disk displacements. Further improvements may be obtained by double-contrast and digital subtraction techniques. In chronic arthritic diseases such as rheumatoid arthritis, the literature has focused on bone abnormalities depicted with tomography and computed tomography. The potential of magnetic resonance imaging to show other inflammatory changes also has been indicated. PMID- 1520930 TI - Osseointegrated implant prosthodontics. AB - This review covers recent literature on prosthodontic aspects of osseointegrated implants. Long-term prognosis, diagnosis and treatment planning, and clinical impression techniques and fabrication technology are discussed. PMID- 1520932 TI - Bibliography of the current world literature. Restorative dentistry. PMID- 1520931 TI - Bibliography of the current world literature. Periodontology. PMID- 1520933 TI - Metalloproteinases in the pathogenesis of periodontal diseases. AB - Matrix metalloproteinases are produced by both defense and structural cells of the periodontium. They are capable of a wide range of interstitial tissue degradation activities. Complex regulating mechanisms include cytokine regulation of genetic transcription, secretion in latent form, which requires activation once produced, and inhibition by specific inhibitors. It appears that these proteinases and their inhibitors, regulating molecules, and associated genetic material are all potential diagnostic markers of periodontal disease. In addition, they can be measured from gingival crevicular fluid or whole saliva. Generally, high inhibitor levels indicate health, and high levels of metalloproteinase indicate disease. Metalloproteinases can also be inhibited by the tetracycline family of drugs to produce clinical benefits. The diagnostic and therapeutic potential of matrix metalloproteinases and their central role in the pathogenesis of periodontal disease serve to emphasize their importance to periodontologists. PMID- 1520934 TI - A review of the developments in dental CAD/CAM systems. AB - At least 1000 CAD/CAM (computer-aided design and computer-aided manufacturing) systems for producing restorations are in dental offices. At least nine different systems have been described; the Cerec system (Siemens, Bensheim, FRG) is the best known and most widely used. Clinical results to date suggest that the automated CAD/CAM systems can provide restorations which perform at least as well as cast restorations. There are some technique sensitivities that must be managed with the new technology. The importance of fit at the margins is a controversial issue that remains to be settled. Bond strength of composite-luted restorations is dependent on margin location and luting material properties, and on the combination of silanating, etching, and curing mechanism of the luting composite. Surface finishes equivalent to cast gold and glazed porcelain can be achieved for machinable CAD/CAM materials. PMID- 1520935 TI - Diagnosis and treatment of refractory periodontitis. AB - Clinicians are occasionally frustrated in arresting the progress of periodontal destruction. The refractory lesion is a problem with a complex and incompletely articulated cause that results in ill-defined and often misdirected treatment. This paper discusses whether refractory periodontitis is a specific entity or whether other periodontal conditions can become refractory. PMID- 1520937 TI - Periodontal disease activity. AB - Periodontal disease activity is defined clinically by progressive loss of probing attachment and radiographically by progressive loss of alveolar bone. The natural history of periodontal disease was originally considered to be nearly continuous and slowly progressive. Clinical research conducted in the last decade suggests that periodontal disease demonstrates periods of exacerbation and remission. Using sensitive automated probes, studies published during the past year have demonstrated that different patterns of disease activity can exist, and that these patterns may be dependent on the disease threshold. Subtraction radiography continues to be refined, but cost and methodology prevent this diagnostic tool from having widespread clinical application. A variety of clinical, microbiologic, and host-response parameters have been studied for their relationship to periodontal disease activity. Many research groups are attempting to develop a diagnostic test that identifies the risk for development of active disease. A relatively simple test based on the presence of a microbial virulence factor, or the host inflammatory or immune response to the subgingival microflora, may be a practical means for clinicians to detect the active phases of periodontal disease. PMID- 1520936 TI - Aesthetic partial-coverage dental restorations. AB - The literature on the subject of aesthetic partial-coverage restorations, including laminate veneers, laminate veneer bridges, composite-resin and ceramic inlays and onlays, computer-designed restorations, and etched cast restorations, has continued to expand into the 1990s. Investigations regarding fit, longevity, wear, and microleakage, as well as descriptions of clinical techniques, were well documented world-wide in 1991. The purpose of this review is to discuss some of the more important papers published during the past year. PMID- 1520938 TI - New considerations in the prevalence of periodontal disease. AB - International surveys demonstrate that the prevalence of pocketing of 6 mm or more is between 5% and 20% for much of the world's population. A recently completed national survey of employed adults found the prevalence of gingival bleeding was 44%, the prevalence of pocketing of 4 mm or more was 14%, and the prevalence of attachment loss of 3 mm or more was 44%. Risk indicators for a higher prevalence of periodontal disease include increasing age, poor education, lack of professional dental care, previous periodontal destruction, tobacco use, and diabetes. African-Americans show a higher prevalence of juvenile periodontitis and adult periodontitis than whites. The female-to-male ratio in juvenile periodontitis may be close to 1:1. Another report during the review period suggests that periodontal disease in adults may have a strong genetic component. A doctoral dissertation demonstrated that the sensitivities of methods used in a national survey to detect pocketing and attachment loss range from 0.24 to 0.87 in a high-prevalence population. PMID- 1520939 TI - Diagnostic tests for periodontal diseases. AB - A high level of interest in the development of diagnostic tests capable of detecting factors associated with progressing ("active") periodontal disease has continued in the past year. Notable advances and refinements have occurred in subtraction radiographic techniques and in the development of computer-linked, controlled-force periodontal probes. Development and evaluation of new diagnostic tests have also proceeded at a rapid pace. Particular emphasis has been placed on rapid tests for putative periodontal pathogens and detection in gingival crevicular fluid of host-derived enzymes. An intense effort must be made to determine the clinical value of diagnostic tests in longitudinal studies that use state-of-the-art assessments of disease progression. PMID- 1520940 TI - Occlusal philosophies and gnathologic instrumentation. AB - The field of occlusion continues to be prolific in publications. While no major advancement in the field was noted in the 1-year period of review, existing concepts and instrumentation continued to be refined. Topics covered in this review include occlusal tooth contacts, choice of alternate occlusal schemes, evaluation of gnathologic instruments and techniques, vertical dimension of occlusion, and mandibular flexure eliminate occurring on opening. PMID- 1520941 TI - Considerations for planning for and fabricating complete dentures. AB - During the past year, studies have been completed to advance our knowledge of the diagnosis and treatment of the edentulous patient. The need for pretreatment radiographs on every edentulous patient is not always indicated. Advances in preprosthetic surgery help to improve the predictability of these procedures. New techniques for establishing the vertical dimension of occlusion may allow this to become a more objective measurement. Evaluation of dental materials for use with complete dentures continues, with soft liners and the use of microwave energy for curing denture resin just two areas of interest. A recent study showed a very high prevalence of signs and symptoms of craniomandibular disorders among complete denture wearers. Methods for its treatment are discussed. The use of increased infection control procedures in the dental office and laboratory have created a need to evaluate the effects of disinfecting agents on the dental prosthesis. The removable complete denture remains an effective alternative for the replacement of missing teeth. PMID- 1520942 TI - The potential role of controlled-release delivery systems for chemotherapeutic agents in periodontics. AB - Following advances in periodontal disease etiology and pathogenesis, treatment strategies have evolved to eliminate specific pathogens or suppress the destructive host response. Research indicates that chemotherapeutic agents such as antimicrobials and antimetabolites can alter disease progression; consequently, three delivery systems have been investigated: systemic, topical, and controlled release. Using polymers to control drug administration, controlled release delivery systems theoretically produce concentration profiles that are more constant and longer lasting than those of other systems. Furthermore, patient compliance can be maximized, and systemic complications avoided. During the past two decades, numerous investigations have been conducted to evaluate the potential role of controlled delivery in periodontal treatment. These investigations fall into two distinct categories: those documenting release kinetics, and those documenting clinical effects. Accordingly, pharmacologic agents can be released from drug polymers at therapeutic levels within the periodontal pocket. Many researchers have demonstrated that controlled delivery of antimicrobial agents such as tetracycline, metronidazole, and chlorhexidine can be effective in reducing the signs of periodontitis. In addition, controlled release of antimicrobial agents can alter the periodontal flora with a decrease in total bacterial mass and pathogenic species. Although the majority of these studies are proof-of-principle trials, many agents have been evaluated with undefined hypotheses, ill-suited outcome variables, unrepresentative patient populations, poor controls, and less-than-ideal therapy applications. The true test of controlled delivery will be the demonstration of its slowing disease progression. While future research will concentrate on developing more ideal polymers and introducing new agents, controlled delivery offers clinicians a potential adjunct or alternative to traditional treatment modalities. PMID- 1520943 TI - A predoctoral honors program in prosthodontics. AB - Over the last 25 years, the advent of new disciplines in dental education and the increasing body of knowledge in various dental specialties have led to a struggle for curriculum hours within many dental schools. At the same time, the amount of time available for teaching clinical skills in dental schools has not increased appreciably, and fewer patients require (or can afford) sophisticated prosthodontic treatment. As a result of these trends, there has been a general decline in the depth and range of clinical skills of recent dental school graduates, particularly in prosthodontics. New York University College of Dentistry has attempted to address this problem by establishing a predoctoral honors program in prosthodontics. PMID- 1520944 TI - Diagnostic procedures for evaluating pulpally involved teeth. AB - Pulpal and periapical problems are often difficult to diagnose because of seemingly conflicting or unclear symptoms. This difficulty increases when there is an emergency situation, and improper diagnosis can lead to improper treatment, causing distress to both the patient and clinician. Because the histopathologic condition of the pulp cannot be determined with clinical means or other diagnostic data, the clinician should focus on making an accurate clinical diagnosis using the patient's history and description of pain, clinical examination, and various diagnostic tests. This review discusses these factors and stresses the importance of making an accurate diagnosis. PMID- 1520945 TI - Current endodontic instruments, materials, and drugs, and new techniques for their application. AB - Technical improvements in endodontic instruments, materials, and drugs and the development of new techniques for their application present a problem for dental practitioners in the selection of materials and methods appropriate to their needs. Claims of "superior" products and "state-of-the-art" treatments only add to the confusion. A review of the dental literature reveals that there is seldom a consensus of opinion on any given subject. Preferences among individuals may reflect a desire for a less complicated, more rapid approach to endodontic treatment. Trends in thought among researchers may offer some direction in the choice between changing concepts and traditional methodology. PMID- 1520946 TI - The potential contributions of cell and molecular biology to periodontal tissue regeneration. AB - Periodontal disease results in the gradual loss of supporting periodontal tissues, and ultimately, the teeth. Although conventional periodontal therapy can arrest the progression of the disease and allow healing, the resulting tissue is unlike that of the normal, healthy periodontium. Cellular and molecular biologic techniques may facilitate our understanding of the regeneration of the periodontium. This review discusses recent findings in cellular and molecular biology relevant to the biology of periodontal tissue regeneration. PMID- 1520947 TI - Pulpal response to restorative procedures and materials. AB - This paper reviews the pulpal response to common restorative procedures and dental materials. Pulpal inflammation and dentin hypersensitivity are commonly associated with routine restorative procedures. Although it is not possible to avoid injury to the pulp completely, in order to prevent unnecessary adverse effects, the practicing dentist should be aware of the potential dangers involved. This article provides a current review of recent findings of the pulpal response to glass ionomer cements and acid-etch composite resin materials. PMID- 1520948 TI - Post and core restoration of endodontically treated teeth. AB - This review discusses the multifactorial nature of tooth strength and concludes that endodontic treatment alone does not weaken intact anterior teeth. Therefore, restoration of such teeth does require post placement or full-coverage restorations. Posterior teeth, however, require full-coverage protection. It appears that the full-crown restoration "covers up" some of the disadvantages or deficiencies of some post and core restorations. The literature supports the use of the amalgam coronal-radicular core or the post-retained amalgam core, as well as the composite post and core. The literature does not support use of the glass ionomer post and cores. As to which post system to select, the literature indicates that the parallel-sided, serrated Para-Post or Para-Post plus is a safe post when seated passively in the canal and cemented with zinc phosphate cements or composite resin cement, or when retained with amalgam. Dentin-retained, stress producing posts such as the threaded posts should be avoided. PMID- 1520950 TI - [To publish in French or in English? That is the question ...]. PMID- 1520949 TI - [Neurosarcoma associated with Von Recklinghausen disease: apropos of 25 cases observed at the Gustave Roussy Institute from 1967 to 1990]. AB - In the absence of systematic immunohistochemistry investigations, only 25 cases (out of 69) clearly diagnosed as neurosarcoma due to the association with Von Recklinghausen disease (ie, neurofibromatosis type 1) and treated at the Institut Gustave Roussy were included in the present study. Neurosarcoma consists of a neurocristopathy whose cells migrate to several parts of the body in order to constitute neuroglia, Schwann cells, pigmented and endocrinal tissues. From 1967 to 1990, 25 cases of such neurosarcomas associated with a neurofibromatosis type 1 were seen at our institute. Three different histological terms exist for this tumour: malignant schwannoma, neurosarcoma, and more recently, malignant peripheral nerve sheath tumours (MPNST). The median age (23 years) of the patients with neurofibromatosis type 1 is lower than that of patient with isolated neurosarcoma. Their sex ratio is 2/1. Primary tumour surgical exeresis was performed in all cases, with poor results in 7. Post-operative radiation therapy was not systematically used in this series. It was administered only in cases with incomplete surgical exeresis or when a local recurrence occurred. Adjuvant CYVADIC (doxorubicin, procarbazine, cyclophosphamide, vincristine) chemotherapy was administered in 5 cases, of in cases of relapse (8). All cases but 2 (the most recent ones) relapsed within 1 to 226 months (median 7 months). In addition, 13 patients developed metastases. Overall, the 2-year and 4-year survival rates were 41% and 18%, respectively. Our observations confirm the very poor prognosis for the association of neurofibromatosis type 1 and neurosarcoma. This finding should lead to systematically associate radical surgical exeresis, post-operative irradiation and adjuvant chemotherapy in the treatment of these patients. PMID- 1520951 TI - [Characterization of autoantigen (p105) in a model of colonic adenocarcinoma in the rat]. AB - Sera from BDIX rats bearing the syngeneic colon tumors PROb or REGb were analysed by Western blotting in order to detect a possible humoral response against the grafted tumor. The PROb clone grows progressively in syngeneic hosts and metastasizes, whereas the REGb clone grows slowly and then is rejected. This model was developed by F Martin and his group in Dijon, France. We observed that rats bearing PROb tumors only develop an antibody response against a water soluble protein of 105 kDa (p105) which is expressed by both tumor clones. This antibody response has never been detected in rats bearing REGb tumors. The antigen p105 was also expressed by normal adult colon as well as some other foetal or adult tissues. It is also present in extracts from several tumor cell lines including human colorectal carcinoma cell lines. Moreover, the titer of detected antibody at day 30 was inversely correlated with the survival of rats after tumor inoculation, suggesting a possible facilitating role of this antibody response. PMID- 1520952 TI - [Risks of cancer among workers of the nuclear industry]. AB - The epidemiological studies on cancer incidence or mortality among workers in the nuclear industry have been reviewed in a comparative manner. The results concerning workers monitored for external radiation or internal contamination and those on female workers have been analysed separately. A lower cancer risk was found in most studies, which is explained by the "healthy worker effect"; no difference was found between the workers with or without a radiation record. A high rate was found for a few cancers at specific sites, but results were variable in the different studies and no relationship was found between cumulative dose and excess mortality due to cancer. A link between ionizing radiation, multiple myeloma and prostatic cancer was indicated in more than one study; in the latter case, there might be a relationship with internal contamination, especially by tritium. In spite of the difficulties and limitations involved, it is important to pursue these studies and pool them, in order to directly evaluate the risks of cancer following exposure to low-dose radiation and low dose rates, instead of calculating these by extrapolation from high doses. PMID- 1520953 TI - [Analysis of changes in serum levels of TNF, IL-1 and IL-6 during administration of IL-2. Correlation with clinical response to treatment]. AB - We have investigated the serum concentrations of TNF, IL-1 and IL-6 in 49 patients with metastatic renal carcinoma receiving interleukin 2 (IL-2) or a combination of IL-2 and interferon alpha (IFN). Our results demonstrate that IL-2 and/or IFN induce an increase of serum concentrations of IL-1 and TNF in 95% and 75% of the patients respectively. Serum IL-6 levels increase in 44% of the patients. Serum concentrations of IL-1 and TNF remain elevated 48 hours after the end of IL-2 infusion. IL-1 and TNF levels are higher in patients receiving a combination of IL-2 and IFN. TNF and IL-1 levels in serum are significantly higher in responders to IL-2 treatment 48 hours after the end of IL-2 infusion. These two biological criteria enable a subgroup of patients with a very low response rate to IL-2 to be defined. The persistent increase of these cytokines in serum indicates a persistent activation of the immune system lasting after the end of IL-2 treatment which could be involved in the antitumor response. PMID- 1520954 TI - [Cytology in the positive diagnosis and grading of prostatic cancers: which indications do remain at the time of automatic biopsies and endorectal echography?]. AB - The diagnostic sensitivity (Se) and specificity (Sp) of fine-needle aspiration cytology (FNAC) of the prostate can be evaluated by comparing its results to a histological reference: rates of reported Se range from 65-98%, Sp being equal or superior to 95%. Published series are heterogeneous in terms of cancer prevalence, with a 25-85% proportion of histologically proven adenocarcinomas, irrespective of the anatomical stage of the disease. The overall accuracy of screening by core biopsies or FNAC is lower than 5%, and does not justify wide scale application of these tests. In 75%, cytological assessment of the tumor grade correlates with Gleason's histological score and grade. Severe intraductal dysplasias (DIC 3) are probably involved in some of the cytological grade I cases. Ultrasonographic guidance of FNAC is not recommended in comparison with histologically obtained data. The indications for performing FNAC of the prostate should be different from those of standard biopsies: the former should be carried out on suspicious lesions revealed by digital rectal examination or ultrasonography, or in a staging attempt. FNAC should be reserved for early diagnosis of prostate cancer in patients presenting with non-specific urologic symptoms. Samples should be obtained by digitally-guided transrectal bilateral FNAC. PMID- 1520955 TI - [Cytotoxic effects of the combination of a new nitrosourea, fotemustine, combined with 5-fluorouracil and folinic acid depend on the sequence of their administration]. AB - The present study was designed to analyse the cytotoxic effects of the combination of fotemustine plus 5-fluorouracil (5-FU) and folinic acid (FA). Two human tumor cell lines were used; one line was derived from colon cancer (WIDR) and the other from a non-small cell lung cancer (CAL 12). Cytotoxic effects were assessed by the MTT semi-automated test in 96-well incubation plates. The effects of various drug combinations were evaluated by the isobologram method. The drug combinations tested included fotemustine concentrations of 20, 30, 40, 50 and 70 micrograms/ml, 5-FU concentrations of 5, 15 and 30 micrograms/ml, and a constant FA concentration of 10(-5) M. A total of 180 different experimental conditions were tested. When cells were exposed to fotemustine before 5-FU the final cytotoxic effects for both cell lines were additive or synergistic in the majority of cases (P less than 0.001). The 5-FU concentration was a determinant factor affecting modification of the effects of the drug combination from antagonism (with low 5-FU concentrations) to synergism (high 5-FU concentrations) (P less than 0.001). Addition of FA (10(-5) M) resulted in a significant shift towards synergistic associations for both cell lines. Administration of 5-FU before fotemustine caused a marked antagonism which 10(-5) M FA was unable to significantly shift towards simple additivity. PMID- 1520956 TI - [Extramammary carcinoid tumor metastatic to the breast. Apropos of a case]. AB - We report the case of a 42-year-woman treated for an appendicular carcinoid tumor with bilateral ovary metastases and mesenteric node involvement. After a systematic mammography, an infraclinical lesion of the breast was detected. Mammographic and echographic images revealed nodular mass with possibly malignant features. Fine-needle aspiration biopsy indicated malignancy. The definitive diagnosis of breast metastasis of a carcinoid tumor was made by biopsy. This case is related to 14 previously published cases. The authors emphasize the importance of making a precise histological diagnosis to avoid overtreatment of a metastatic lesion. PMID- 1520957 TI - The characterization of two new low molecular weight proteins (LMPs) from Streptococcus pyogenes. AB - Two novel extracellular mitogenic substances were isolated from Streptococcus pyogenes strain NY-5 and characterized. The purification steps involved an initial enrichment of the proteins from culture supernatant by silica gel adsorption, followed by ion exchange chromatography and gel filtration. The purified materials were homogeneous in SDS-PAGE, showed estimated molecular weights of 12 kD and isoelectric points of 4.7 and 4.3, respectively. Both proteins (LMP-12k-4.3pI and LMP-12k-4.7pI) demonstrated lymphocyte transformation activity at a concentration of 0.1 microgram/ml. The LMP-12k-4.7pI showed a 69.2% homology of the amino acid sequence with that of a phosphocarrier protein of Staphylococcus aureus and with a total identity in the active centre. The same protein was also isolated from streptococcal group C strain H46A with an N terminal amino acid sequence being identical. The LMP-12k-4.7pI demonstrated biochemical properties identical with those of the earlier described streptococcal pyrogenic exotoxin type D. The LMP-12k-4.3pI did not show such a clear relation to other functional proteins. PMID- 1520958 TI - Characterization of the virulence regions in the plasmids of three live Salmonella vaccines. AB - Three live Salmonella vaccines, Zoosaloral "Dessau", Bovisaloral "Dessau", and Suisaloral "Dessau" successfully used in veterinary medicine in eastern Germany were analysed for their plasmid DNA content. Plasmids of 60 MDa (S. typhimurium), 55 MDa and 26 MDa (S. dublin) and 34 MDa (S. choleraesuis) were found. The three large plasmids contained a virulence region as shown by restriction enzyme analysis and hybridization studies with virulence-region-specific DNA probes. Restriction enzyme pattern analysis of the whole plasmids revealed differences between vaccine strains and parental strains. We wanted to know if there were alterations within the virulence region of the vaccine strain plasmids compared with parental strains caused by the attenuation procedure. Therefore, the 6 kb Cla I fragments of several plasmids were cloned and characterized by restriction enzyme fingerprinting. The expression of the Cla I fragment-encoded proteins was analysed in the minicell-producing strain DS 410. The experiments revealed that the restriction pattern of the 6 kb-Cla I fragments of Zoosaloral and Bovisaloral as well as the PAGE pattern of virulence-region-encoded proteins were in complete accordance with one another, between vaccine strains and the parental strain of Zoosaloral, and with a wild-type strain of S. typhimurium. PMID- 1520959 TI - In vitro activity of antifungal agents against clinical isolates of aspergilli. AB - The growth-inhibitory effect of 9 antifungal agents against 32 strains of aspergilli belonging to 10 species was studied. MIC values were determined in a microtiter dilution method using Brain Heart Infusion Broth (polyenes, azoles) and a medium with Yeast Nitrogen Base (5-flucytosine). Saperconazole was the most active agent against all isolates tested, the growth of 90% being inhibited at a concentration of 0.09 mg l-1. The susceptibility profile of individual species differed only little, with the exception of high MIC values of polyenes in A. terreus. Nine isolates (28%) were resistant to 5-flucytosine. The intra-species variation of susceptibility studied in A. fumigatus was only little pronounced. PMID- 1520960 TI - Human giardiasis: correlation of specific secretory IgA levels in duodenal fluid to the severity of disease and infestation by Giardia lamblia. AB - Giardia lamblia specific secretory immunoglobulin A (sIgA) levels in the duodenal fluid of adult giardiasis cases are reported for the first time. The sIgA levels in the study group were found to be significantly higher (p less than 0.01) than in the 20 age- and sex-matched controls comprising cases classified as non ulcerative dyspepsia who did nor reveal any G. lamblia in their stools and the duodenal fluid. An inverse relationship between the clinical severity of giardiasis and the level of sIgA in the duodenal fluid was noted. Cases with a higher trophozoite load in duodenal aspirate tended to be associated with envanescent G. lamblia-specific antibodies. PMID- 1520961 TI - Varying incidence of Blastocystis hominis in cultures from faeces of patients with diarrhoea and from healthy persons. AB - A study was performed on the frequency of Blastocystis hominis in the faeces from 100 patients suffering from diarrhoea and from 100 healthy persons. Surprisingly, an increased detection rate was observed in samples from healthy persons after anaerobic cultivation. This increased frequency is obviously not dependent on the kind of serum used as a culture supplement and raises the question whether the protozoa morphologically described as B. hominis represent a homogenous species. When rabbit and horse sera were used instead of human serum for cultivation, in both groups the share of positive cultures increased and more large forms of B. hominis cells were observed. Biological implications are being discussed. PMID- 1520962 TI - Diagnosis, prevalence and drug resistance of mycobacteria in HIV-positive and HIV negative patients of an urban population in Germany. AB - In a survey of 3004 clinical specimens from 1112 HIV-negative and 679 clinical specimens from 140 HIV-positive patients which were submitted to our mycobacterial laboratory, we have analysed the different diagnostic approaches concerning mycobacterial disease in these two populations. We have assessed specimen-type, culture result, microscopical diagnosis and prevalence in relation to HIV status. Isolation rates of mycobacteria were highest in blood cultures from HIV-positive patients. 10 out of 140 HIV-positive patients had positive mycobacterial culture results. All 10 had positive blood cultures, but only three of them were positive for M. tuberculosis. PMID- 1520963 TI - Salmonella enterica: infection, cross infection and persistence within the environment of a broiler parent stock unit in Denmark. AB - A total of three hundred and ninety nine isolates of Salmonella enterica were recovered from 3106 cloacal swab cultures, chicken carcasses and environmental samples taken from a broiler breeding farm over six successive generations. S. enterica serovars Berta (S. Berta), 4,12:b:-, Taksony, Binza and Typhimurium were identified. One hundred and seventy one strains of S. Berta were analysed by plasmid profiling to determine the epidemiological relationships between isolates from each generation and from each house section of the production unit. All isolates contained plasmids; plasmids of eleven different molecular weights were identified. Eighteen different plasmid profiles were identified throughout the observation period. An increase in the diversity of plasmid profiles in each successive generation, the restriction of particular plasmids to particular houses and their persistence within that house were taken to indicate that contamination within the unit was due to persistence and cross-infection rather than to a reintroduction of serovar Berta into new generations of stock. PMID- 1520964 TI - Aerogenic pasteurellas and Pasteurella-like organisms isolated in Czechoslovakia. PMID- 1520965 TI - Identification of aerobactin genes in clinical isolates of E. coli using a non radioactive DNA probe. AB - A digoxigenin-labelled gene probe was used for the identification of aerobactin genes in 21 E. coli strains from clinical isolates by means of a colony hybridization test. The results were compared with those obtained by previous hybridization experiments with radiolabelled DNA probes as well as with a crossfeeding-assay. It could be demonstrated that only after an additional proteinase K treatment of the filters before hybridization and after a repeated blocking during the immunological detection procedure, specific hybridization signals could be observed. PMID- 1520966 TI - Polymorphism of outer surface proteins of Borrelia burgdorferi as a tool for classification. AB - A total of 23 isolates of Borrelia burgdorferi were characterized by SDS-PAGE and immunoblot analysis. One isolate came from the CSF of a Lyme neuro-borreliosis patient in Valais (Switzerland) and 22 were tick isolates (2 from I. dammini of Shelter Island, USA and 20 from I. ricinus of Valais, Switzerland). Based on the electrophoretic mobility of outer surface proteins (OspA and OspB), four groups of B. burgdorferi could be defined. Group I isolates possess an OspA of 31 KD and an OspB of 34 KD. The group II isolate showed an OspA of 32 KD and OspB of 35 KD. Group III isolates have a 33 KD OspA and group IV a 33.5 KD OspA. This classification was confirmed by the reactivity of a monoclonal antibody (D6) to a 12 KD antigen that was recognized in group III only. A Lyme patient's serum showed a 2-band pattern (10 and 13 KD) for group I and a one-band pattern (12 KD) for the other 3 groups. Therefore OspA, OspB and other proteins of low molecular weight (10, 12, and 13 KD) seem to be important keys for the classification of B. burgdorferi isolates. This typing system correlates with genetic analysis. PMID- 1520967 TI - Lack of immunoglobulin A1 protease production by Haemophilus ducreyi. AB - A collection of 20 strains of Haemophilus ducreyi including freshly isolated, low passage and multi-passage reference strains was examined for immunoglobulin A1 protease production by SDS-PAGE and immunoblotting. None of the strains demonstrated IgA1 protease activity despite the fact that different culture media were used. By direct immunofluorescence testing, binding of IgA to Haemophilus ducreyi organisms could be demonstrated. PMID- 1520968 TI - Monoclonal antibody based capture ELISA/ELIFA for the detection of Chlamydia psittaci in veterinary clinical specimens. AB - A capture ELISA/ELIFA system based on monoclonal capture and biotinylated monoclonal detection antibody with specificity for an epitope on chlamydial lipopolysaccharide (LPS) is described. The assay is fast, specific and detects a minimum dose of approximately 2000 chlamydial particles (C. psittaci). Unlike other commercially available test kits, it comprises a proteinase K treatment to exclude non-specific binding of antibodies to Fc receptors. In contrast to the sophisticated and cumbersome isolation procedures, even non-specialized laboratories may use this assay system for the investigation of clinical samples of different origin for the presence of C. psittaci within a short period of time. Due to the genus specificity of the monoclonal antibody used C. trachomatis and C. pneumoniae can be detected as well. PMID- 1520969 TI - Detection of Mycoplasma contamination in primary calf kidney cell cultures. AB - A total of 31 primary cell culture preparations of calf kidney including their processing stages (kidney, washing fluid, cell suspension, cell culture monolayer) were investigated for mycoplasmas by cultural methods. Mycoplasma (M.) arginini, was isolated from 8 out of 27 investigated samples of calf kidney from 3 out of 26 washing fluids, 5 out of 20 cell suspensions, and from 9 out of 21 cell culture monolayers. Furthermore, M. arginini was repeatedly found in throat swabs of the cell laboratory technicians. The results give indications as to the source and route of mycoplasma infections of primary cell cultures. PMID- 1520970 TI - Pertussis whole cell vaccine: relation between intracerebral protection in mice and antibody response to pertussis toxin, filamentous hemagglutinin and adenylate cyclase. AB - N:NIH mice were vaccinated according to the WHO recommendations for the potency test with the Second International Standard for Pertussis Vaccine (ISPV). Blood for serological investigation was taken from the animals on day 14 post immunization before intracerebral challenge with Bordetella pertussis 18323 was done. The relationship between anti-pertussis toxin, anti-filamentous hemagglutinin and anti-adenylate cyclase antibody levels as measured by ELISA and protection from intracerebral challenge was studied. The proportion of surviving mice increased in correlation with increasing anti-PT titres; a protective level of 4 ELISA units/ml was found. Such relationship between protection against intracerebral challenge and antibody titres was not found for anti-FHA nor for anti-AC antibodies, thus suggesting that these antibodies do not play an important role in protection in this model. The excellent correlation between anti-PT antibody titres and protection suggests that the measure of anti-PT response could be a useful tool for estimating the potency of whole-cell vaccines. The development of an alternative method for testing the potency of pertussis whole-cell vaccines based on the anti-PT response should be considered. PMID- 1520971 TI - Urinary tract infection due to a mucoid (M) form of Salmonella. A "new" transformation from M form into T1 form. AB - An eighty-year-old patient suffering from prostatic hypertrophy developed cystitis associated with fever, macrohematuria and significant bacteriuria. In urine cultures, growth of a mucoid (M) form of Salmonella was seen which changed into a T1 form after having been stored at room temperature or passed through U tubes. While the M form did not agglutinate in Salmonella O and H antisera, H antigens of the T1 form could be identified as l,v and 1.7. The isolate was therefore designated S.I M----T1:l,v:1.7. To date, no such M-T1 variation has been described. For diagnostic and epidemiologic purposes Salmonella M forms should be transformed into the N form or a T form (as in our case), because it is possible to demonstrate O or T and H antigens in these forms. The method of transformation and the pathogenesis of urinary excretion of salmonellae are briefly described. PMID- 1520972 TI - A simplified agarose gel electrophoresis for rotavirus detection. AB - The use of agarose gel electrophoresis for rotavirus detection is a suitable routine method if simplifying modifications are introduced. Incorporation of ethidium bromide into the agarose gel permits its use for several times in the course of one week without further staining of the RNA segments. The electrophoresis chamber with a UV-light-transparent bottom is put directly onto the transilluminator and the RNA bands of the rotavirus can be visualized without manipulating the gel tray. During the winter of 1990/91, we found a good sensitivity (98%) of this method in comparison to a latex agglutination test (Slidex Rota-Kit 2, bio Merieux). PMID- 1520973 TI - A 41.7 kDa serine protease from Clostridium perfringens type A: degradation of purified human serum proteins. AB - Two clinical isolates of Clostridium perfringens type A produced a novel caseinolytic serine protease. Both enzymes had a molecular weight of 41.7 kilodaltons and an isoelectric point of 9.1. The two enzymes were immunogenic for rabbits and closely related serologically. Both enzymes partially degraded the heavy chains of human immunoglobulins (Ig) G and IgM, but not IgA. Purified human complement (C) components C3, C5, C8, and C9 were attacked; C1q was refractory. Both enzymes were active against human transferrin, alpha 1-antitrypsin, alpha 2 macroglobulin, haptoglobin, type III fibrinogen, and fibronectin. C-reactive protein was refractory. PMID- 1520974 TI - Optimization of culture conditions for toxin production of type G Clostridium botulinum. AB - Culture conditions were optimized for toxin production of Clostridium botulinum type G, the last toxigenic serotype described. Six factorial experiments were performed to assess the effect of medium composition (nutrients, metal ions, sterile soil, pH), incubation conditions (time, temperature and anaerobiosis) and associated microorganisms (Bacillus subtilis, Lactobacillus plantarum) on the toxinogenesis of C. botulinum type G. A significant (4 to 10 fold) improvement of toxin production was obtained by using an optimized medium (3% proteose-peptone, 0.5% trypticase, 1.1% glucose, 0.5% yeast extract, adjusted to pH 8.0) and incubation of the culture for 12 days at 26 degrees C in a nitrogen atmosphere. PMID- 1520976 TI - Subtyping of Legionella pneumophila serogroup 1 strains isolated in Germany using monoclonal antibodies. AB - Legionella pneumophila serogroup 1 (Lp1) strains isolated from patients and hot water supplies in different locations of Germany were subtyped using seven monoclonal antibodies (mabs) in the indirect immunofluorescence test (IFA) and in part, using a dot blot assay. Four of these mabs were produced in Dresden. Three mabs (mab 33G3, mab 32A12 and mab 144c2) were kindly supplied by J. Joly, Quebec, Canada. Altogether, seven antigenic variants were found among Lp1 strains isolated in Germany. Patient strains belonged to the Philadelphia, Benidorm, Knoxville, France, Olda-Heysham and Bellingham subgroups, whereas environmental isolates reacted like the Bellingham, Oxford, Philadelphia, Knoxville and France strains. The majority of patient strains (15 out of 26, 58%) reacted with our mab 3/1 (corresponding to mab 2 of the standard panel), but only 26 out of 118 environmental strains (22%) isolated from 4 of 15 hot water supplies did so (p less than 0.05). The majority of water-borne Lp1 strains reacted with a mab specific of the Bellingham subgroup. Three water systems under study were associated with human legionellosis. Two of them contained Bellingham-like strains, one Philadelphia-like legionellae. PMID- 1520975 TI - A sensitive method for the detection of enterotoxigenic Escherichia coli by the polymerase chain reaction using multiple primer pairs. AB - In this study, a polymerase chain reaction (PCR) method has been developed for the detection of enterotoxigenic Escherichia coli (ETEC). Three different sets of oligonucleotide primers synthesized were used to amplify the enterotoxin genes of heat-labile (LTh) and heat-stable (STIa and STIb) enterotoxins of ETEC. These primers amplified a 627, 240, or 169 base pair (bp) DNA fragment from LTh, STIa and STIb gene, respectively, of the reference ETEC strains. The addition of RNase A (10 micrograms/ml) to the PCR reaction solution diminished nonspecific amplification of DNA fragments other than the enterotoxin genes. Five types of ETEC strains corresponding to the LTh, STIa, STIb, LTh-STIa, or LTh-STIb genotypes were distinguished by a single procedure of PCR using the mixture of the three sets of primers. PCR, hybridization, and conventional methods were subjected to one hundred stool specimens from diarrheal patients. It was found that PCR was the most sensitive method among them. These results suggested that PCR with triple primer pairs would be useful for the laboratory diagnosis of ETEC in the stool specimens. PMID- 1520977 TI - Indirect haemagglutination test for the serodiagnosis of brucellosis using stabilised sheep red blood cells. AB - Sheep red blood cells (SRBCs) stabilised with formaldehyde, glutaraldehyde, pyruvic aldehyde and double aldehyde were evaluated, in the indirect haemagglutination (IHA) test, for their suitability for the serodiagnosis of brucellosis in bovines. Serum samples from 23 standard tube agglutination test (STAT)-positive and 12 clinically suspected but STAT-negative cows were titrated by the IHA test. Double aldehyde and glutaraldehyde-stabilised SRBCs were found to be more sensitive in the IHA than the formaldehyde or pyruvic aldehyde stabilised SRBCs. Double aldehyde and glutaraldehyde treatments enabled the IHA to clearly differentiate between the normal and the diseased cows. Double aldehyde-stabilised cells have an edge over the glutaraldehyde-stabilised SRBCs because the former treatment makes the SRBCs readily available for antigen coating without tannic acid activation. PMID- 1520978 TI - Is Escherichia coli invading tubuloepithelial cells? AB - The adhesion of Escherichia coli to host epithelium cells is the very first step of urinary tract infections followed by the internalization of the bacteria into these cells. These steps are influenced by several surface antigens or products of the pathogen, e.g. fimbriae or adhesins, K antigen, and hemolysin. The bacterial adherence and the internalization of several isogenic E. coli O18 strains differing in the expression of K5 antigen, hemolysin, and type of fimbriae were measured by using a permanent line of porcine tubuloepithelial cells (LLC-PK1). Strains with K5 antigen were reduced in their adherence and internalizability as compared to the K-negative strains. The expression of hemolysin by these strains lead to an increase of adherence and internalization. The internalization of bacteria is influenced mainly by their adherence to the epithelial cells. Thus, the engorgement of attached bacteria is rather a kind of endocytosis than an invasion of bacteria. PMID- 1520979 TI - In vitro and in vivo activities of KRM-1648, a newly synthesized benzoxazinorifamycin, against Mycobacterium marinum. AB - The in vitro and in vivo activities of KRM-1648, one of the newly synthesized benzoxazinorifamycins, against M. marinum were compared with those of rifampin. The MIC values of KRM-1648 determined by the agar dilution method on 7H11 medium against 10 strains of M. marinum were 32-128 times and even more below those of rifampin. In an in vivo experiment, KRM-1648 was markedly effective in terms of the incidence of gross skin lesions and the number of CFUs in the lungs and spleen. Its efficacy was much greater than that of rifampin. PMID- 1520980 TI - The clinical significance of Acinetobacter baumannii in blood cultures. AB - Acinetobacter baumannii was isolated from blood cultures in 31 patients in 4 intensive care units at a large teaching hospital over a period of 6 months. In 23 of these patients, Acinetobacter was also isolated from tracheal aspirates. Catheter-related infection could be identified as the cause of bacteremia in 14 cases, whereas pneumonia was present in only 6 cases. All patients were seriously ill and 7 (24%) died of their infection. PMID- 1520981 TI - Heat stability of parvovirus B19: kinetics of inactivation. AB - Heat inactivation of parvovirus B19 (B19) was studied in a culture of hematopoietic progenitor cells generated in vitro from peripheral human blood. After inoculating cell cultures with identical volumes of plasma (MII) containing B19 (B19-MII) heat-treated (60 degrees C) for various periods of time, a time dependent inactivation of the input virus was determined by a decrease of viral DNA replication. No B19 DNA was detected after infection with B19-MII heat treated for 20 min or more by Southern blot. Viral B19 protein production decreased time-dependently and was not detected after infection with samples treated for 12 min at 60 degrees C or more determined by the enzyme immunoassay. This study indicates that infectivity of B19 virus in plasma can be reduced in vitro by heat-treatment (60 degrees C). However, this does not mean that the heat treatment completely inactivated B19 virus. PMID- 1520982 TI - Epidemiology and ecology of tick-borne encephalitis in the eastern part of Germany between 1960 and 1990 and studies on the dynamics of a natural focus of tick-borne encephalitis. AB - From 1960 to 1990, attempts to isolate TBE virus from ticks and small mammals were made and investigations to detect TBE antibody in small mammals, game and humans were performed in the five new federal Lander of Germany. The confirmed TBE cases for which the site of exposure could be determined were also registered. As a result of these epidemiological and ecological investigations, a map is presented showing the natural foci of TBE which are primarily located in the subatlantic and mountainous climatic regions. TBE was endemic in the area of investigation from 1960 to 1990 showing a morbidity of up to 0.7 per 100,000 inhabitants which decreased in recent years to 0.02 per 100,000 inhabitants. The natural foci of TBE virus in eastern Germany showed a high activity between 1960 and 1970. Since that time, there have hardly been any cases of human disease and TBE virus could no longer be detected, neither in ticks nor in small mammals. Taking the natural focus on the Island of Usedom as an example, attempts have been made to elucidate whether such foci have become extinct or whether they have persisted. From 1983 to 1989, a surveillance programme was performed to detect antibodies to TBE virus in small mammals and game and to attempt to culture virus from ticks and small mammals. The attempts to isolate virus from a total of 8200 ticks were negative. Attempts to isolate virus from the brains of small mammals were also negative. Antibody prevalence in 446 small mammals and 500 animals of game was ca. 1%. At one site, the sero-positive reactions converted from 0% (1983 1988) to 4.5% (1989) among small mammals population. The investigations performed on the Island of Usedom have shown that this natural focus has not disappeared but is in a state of endemic latency. Moreover, the seroconversion observed in the small mammals population shows that further surveillance of such foci is necessary. This becomes obvious by the sporadic occurrence of single TBE cases as well as by a low antibody prevalence of 1% in small mammals and game. The epidemiological situation in eastern Germany is thus completely different from that in western Germany where an average of 70-120 TBE cases per year are registered, occurring mainly in Bavaria and Baden-Wurttemberg. PMID- 1520983 TI - Studies on glycolytic enzymes of Plasmodium knowlesi, a simian malaria parasite, and infected host erythrocytes. AB - Almost all of the important enzymes of glycolytic sequence were studied in isolated schizonts of Plasmodium knowlesi as well as in normal and P. knowlesi parasitized rhesus red blood cells. Significant activities of all the glycolytic enzymes assayed were observed in cell-free schizonts and the levels of all were found to be considerably elevated in infected host erythrocytes, confirming that the consumption of glucose is dramatically increased in host red cells, consequent to malaria infection. PMID- 1520985 TI - Serotyping and further characterization of group B streptococcal isolates from Indonesia. AB - Serotyping of 103 streptococci of serological group B isolated from human clinical specimens in Indonesia revealed mainly type pattern Ia/c and type patterns III and V, either alone or in combination with protein antigens c or R. Few cultures had serotype II and IV, none of the cultures had type antigen Ib or X. Extracts of one group B streptococcal culture reacted with antibodies specific to type antigens II, IV and R and one culture with antibodies specific to candidate type 7271. Protein antigen c was present as c alpha, c alpha, beta but not as c beta component. Group B streptococci with type antigen R grew generally as a granular sediment with clear supernatant, formed compact colonies in soft agar and reacted positively in the salt aggregation test. Group B streptococci without surface antigen R grew mainly with a uniform turbidity of the growth media, formed diffuse colonies in soft agar and were negative in the salt aggregation test. PMID- 1520984 TI - Phage susceptibility, enterotoxigenicity and antibiograms of Staphylococcus aureus strains isolated from human wounds and diarrhoea. AB - The phage types, enterotoxigenicity and antibiograms of Staphylococcus aureus strains isolated from human diarrhoea and skin wounds in Nigeria were determined. Of 194 strains tested, 140 (72.2%) were typable using a combination of phages in the International Phage Set (IPS) for human strains of S. aureus and the bovine phage set. IPS phages lysed 118 (60.8%) strains while 96 (49.5%) were susceptible to bovine phages. S. aureus strains from adult diarrhoea were significantly (P less than or equal to 0.01; x2) more sensitive to bovine phages (52.8%) than to IPS human phages (16.7%). Strains isolated from wounds were however significantly (P less than or equal to 0.001; x2) more susceptible to IPS human phages (72.9%) than to bovine phages (41.5%). Phage group III strains were predominant amongst diarrhoeal isolates while wound strains were most susceptible to group II phages. Phage 119, a bovine phage, lysed all 19 strains of diarrhoeal origin sensitive to group M phages but all wound strains were resistant. Overall, 132 (68.0%) strains were enterotoxigenic producing staphylococcal enterotoxins A (SEA), B (SEB), C (SEC) or a combination of these. A majority of diarrhoeal strains elaborated SEC while SEB production was predominant amongst wound strains. Of the eight antimicrobial agents used, S. aureus strains were most resistant to penicillin (71.6%) and least to sulfamethoxazole/trimethoprim (1.0%). Occurrence of resistance to one or more antibiotics was higher amongst wound strains (97.5%) than amongst strains isolated from diarrhoea (52.6%). It was concluded that bovine phage 119 may be a useful epidemiologic marker for S. aureus strains of bovine origin associated with human diarrhoea in Nigeria. It is however difficult to ascribe any aetiological significance to these strains because other enteropathogens not assayed for may have been present. PMID- 1520986 TI - Postoperative wound infections complicating adult spine surgery. AB - A review of 19 consecutive patients treated for deep wound infections after spinal surgery was performed. Patients were analyzed for preoperative risk factors, original diagnosis requiring surgery, onset of infection, presentation, treatment, and outcome. These patients (10 men, nine women), with a mean age of 44 years (range 18-74) were treated for 13 deep and six subcutaneous infections: 16 spine infections and nine graft site infections (six with both). All 19 presented with draining wounds on an average of 17 days after surgery (range 4 86). Staphylococcus aureus was cultured in 14. Patients were treated with i.v. antibiotics for an average of 3 weeks (range 0-14) followed by oral antibiotics for an average of 6 weeks (range 2-12). Surgical treatment included an average of 1.8 debridements (range 0-5), primary closure in two, delayed primary closure in seven, and healing by secondary intent in 10. All but three patients were noted to be malnourished at the onset of their infection, with a total lymphocyte count of less than 2,000. Three patients required removal of their hardware. Eighteen of 19 healed or their infections were stabilized, 17 of 18 arthrodeses fused, and no patient had neurological deterioration secondary to the infection. The treatment outlined produced satisfactory results in all but one patient. We conclude that postoperative spine infections are frequently associated with poor nutrition. Although definitive diagnosis is determined by the culture, clinical exam is helpful in establishing a presumptive diagnosis and, thus, earlier institution of surgical and antibiotic treatment. PMID- 1520987 TI - Tuberculosis of the spine: a review of 236 operated cases in an underdeveloped region from 1954 to 1964. AB - Antituberculous medication for treatment of tuberculosis has been used for nearly a half century. However, tuberculosis of the spine still shows up from time to time in the developed countries and it is still a common scourge in half of the world today. The author reviews his treatment of tuberculosis of the spine over 30 years' full-time work in developing countries. He gives an analytical breakdown of his first 10 years of operating on 236 cases, both paralytic and nonparalytic. Changes in treatment developed with experience. Posterior spinal fusion gave good results. Radical evacuation of the abscess alone gave poor results. Best results were obtained in the combination of the two. This surgery provided a stable, pain-free spine and shortened period of time that antituberculous medication was required. A true lateral approach for spinal decompression was developed and is described. This procedure can be performed by ordinary orthopedic teams in developing countries. It is safer than the transthoracic approach and gives better exposure. PMID- 1520988 TI - Anatomic and biomechanical study of posterior cervical spine plate arthrodesis: an evaluation of two different techniques of screw placement. PMID- 1520989 TI - Immediate postoperative stability of the atlantoaxial articulation: a biomechanical study comparing simple midline wiring, and the Gallie and Brooks procedures. AB - A biomechanical study was undertaken to quantitate the immediate postoperative stability of the atlantoaxial articulation after stabilization by simple midline wiring, as well as the Gallie and Brooks procedures. Fresh adult cadaveric cervical spines were mounted for testing such that only the C1-2 motion segment and the load deflection curves generated in flexion, extension, and torsion moved. Spines were tested after the creation of a fracture at the base of the odontoid process with transection of the transverse ligament and after stabilization by each of the surgical techniques. Mean apparent stiffness values evaluated the biomechanical properties of these three commonly performed procedures. Although all tested procedures restored supraphysiologic mechanical properties in all modes tested (p less than 0.001), the Brooks technique was stiffer than the other two methods (p less than 0.001). Although many factors must be considered when selecting a particular surgical technique, the biomechanical data obtained in this study may be of assistance to the surgeon in choosing the type of construct for upper cervical stabilization and arthrodesis. PMID- 1520990 TI - The thermoplastic Minerva body jacket: a clinical comparison with other cervical spine splinting techniques. AB - A retrospective analysis of the efficacy of a variety of external stabilization techniques used in 155 cases of unstable cervical spine injuries is presented. The movement at each intervertebral level was evaluated during thermoplastic Minerva body jacket stabilization in 18 additional patients. Many currently available approaches to external stabilization of the cervical spine were, thus, assessed. Thermoplastic Minerva body jacket stabilization offered superior segmental immobilization compared with published data for the halo. It is concluded that some unstable injuries to the high cervical spine might best be treated with a halo device, whereas mid to low cervical injuries and the remaining upper cervical spine injuries appear to be optimally treated with a Minerva jacket. Lesser injuries may be treated with a variety of available orthoses. The thermoplastic Minerva body jacket offers a superior limitation of intervertebral movement compared with other commonly used braces, including the halo jacket, for most cervical spine injuries. The technique of application of the thermoplastic Minerva body jacket is reviewed. PMID- 1520991 TI - Noncontiguous injuries of the spine. AB - A total of 372 consecutive spinal injury patients were evaluated at the Regional Spinal Cord Injury Center of Delaware Valley. Of these, 39 patients (10.5%) were found to have noncontiguous spinal column injuries. Fewer than half of the patients in our series could be classified into previous classification systems (Calenoff, Gupta) of noncontiguous spinal fractures. Fifteen fractures in 12 patients were missed on presentation on admission and 25% of these patients had a progressive neurologic deficit as a result of improper initial immobilization. The location of missed fractures were found to be primarily at the extremes or junctures of the spine (i.e., cervicothoracic, thoracolumbar). Complete spinal roentgenographic evaluation is recommended in the workup of suspected spinal column injury patients, and additional imaging modalities (i.e., tomograms, computed tomography scans, and magnetic resonance imaging) may be necessary in those areas of the spine difficult to visualize. PMID- 1520992 TI - Anterior transpedicular instrumentation of the lumbar spine: an anatomical study. AB - Lumbar burst fractures or massive tumorous destruction of the lumbar spine generally require a combined anterior-posterior surgical approach for adequate decompression and stabilization. Anatomical studies in 10 adult cadavers with 100 pedicle screw placements from a single strictly anterior approach showed that this new method represents a safe and promising way for stable lumbar spine instrumentation, avoiding the risks of a bilateral approach. The technique provides a stability comparable with bilateral instrumentation. Exact knowledge of the geometry of the corresponding vertebral bodies and the spinal canal by computed tomography scanning is a prerequisite for this surgical technique. First clinical applications using this technique reconfirm the experiences of the anatomical study. PMID- 1520994 TI - Cervical spondylolysis. AB - The term cervical spondylolysis describes a long-standing, perhaps congenital defect of the pars interarticularis of a cervical vertebra. We report 10 new cases of cervical spondylolysis and review the literature. All patients in this report were treated nonoperatively with subsequent symptomatic improvement. Cervical spondylolysis must be differentiated from its traumatic counterparts radiographically. Characteristic radiographic findings include well-corticated margins at the defect, a characteristic "bow tie" deformity, and ipsilateral dysplastic facets. Compensatory hypertrophic changes of the adjacent articular processes, spina bifida, and spondylolisthesis are frequently, but not always, seen in conjunction with cervical spondylolysis. The vast majority of patients with radiographically proven cervical spondylolysis can be treated confidently with conservative measures. Surgical intervention should be reserved for those who fail nonoperative management or who exhibit neurologic compromise referable to an unstable spondylolytic defect. PMID- 1520993 TI - Unstable thoracolumbar and lumbar burst fractures treated with the AO fixateur interne. AB - Twenty-five consecutive patients with unstable thoracolumbar and lumbar burst fractures were surgically treated with the AO Fixateur Interne (Synthes USA, 1690 Russell Rd., Paoli, PA). Indications for surgery included a progressive neurologic deficit, spinal canal compromise greater than 50%, vertebral body collapse greater than 50%, or sagittal angulation greater than 20 degrees. Twenty males and five females ranging in age from 16 to 60 years (average 31) were treated surgically and prospectively followed. Twenty-one fractures occurred at the thoracolumbar junction (T10-L2) and 4 in the lumbar spine (L3-5). Twenty-four patients were followed for a minimum of 12 months, ranging from 12 to 38 months (average 22); one patient was lost to follow-up after 1 month postoperatively. Preoperatively, 12 patients had partial neurologic deficits; postoperatively, 11 improved at least 1 Frankel grade. Preoperatively, the 12 patients with partial neurologic deficits averaged 45 points (range 24-49) on the lower extremity motor index scale. After surgery, these patients improved an average of five points (range 1-23) on the motor index scale. Both patients with complete spinal cord injuries remained unchanged neurologically postoperatively; no patients deteriorated neurologically after surgery. The average preoperative sagittal kyphosis at the fracture site was +16 degrees (range +10 degrees to +31 degrees); the immediate postoperative sagittal angular correction averaged -4 degrees (lordosis) and ranged from +12 degrees (kyphosis) to -26 degrees (lordosis). At last follow-up, the sagittal angular correction remained unchanged in three patients and decreased in 21 patients to an average of +5 degrees (range +37 degrees to -14 degrees).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1520995 TI - Esophageal perforation after anterior cervical plate fixation: a report of two cases. AB - We report two cases of esophageal complications due to migration of screws after anterior plate fixation of the cervical spine. Close observation for screw back out is needed, particularly in those patients with associated neurologic deficits or osteoporosis. PMID- 1520996 TI - Central retinal artery occlusion: a complication of the knee-chest position. AB - A rare complication of the knee-chest position used for lumbar disk surgery is reported. Central retinal artery occlusion resulted in permanent loss of vision secondary to direct ocular pressure. Prevention is the only rational treatment for this unfortunate condition. PMID- 1520998 TI - Torulopsis glabrata vertebral osteomyelitis. AB - A case of Torulopsis glabrata osteomyelitis of the thoracic spine producing spinal cord compression and myelopathy is reported. The patient displayed several of the predisposing factors to T. glabrata infection, including diabetes mellitus, a history of abdominal surgery, and intravenous catheterization with hyperalimentation. The patient was successfully managed with surgical decompression, debridement, and curettage of the affected bone, postoperative immobilization, and systemic amphotericin B therapy. Her pain was relieved, spinal cord function recovered, and the vertebrae healed uneventfully. T. glabrata osteomyelitis is a rare and unpredictably progressive infection. This case demonstrates that it requires prompt therapy and close observation. PMID- 1520997 TI - Extraosseous epidural tumor of immunoglobulin D myeloma. AB - We report a rare case of an immunoglobulin D (IgD) myeloma mass that occupied the lumbar epidural space. The patient presented with paraparesis combined with an extremely high concentration of serum IgD, and azotemia. A complete remission was obtained after combination chemotherapy, but the patient died from an epidural tumor in the high thoracic region 19 months after the onset of symptoms. PMID- 1520999 TI - Cervical stenosis: myelopathy hand. PMID- 1521000 TI - Male-mediated teratogenesis and other reproductive effects: biologic and epidemiologic findings and a plea for clinical research. AB - This paper reviews biologic and epidemiologic evidence that prefertilization and perifertilization exposures to fathers influence a variety of reproductive outcomes, including fertilization, miscarriage, low birth weight, congenital anomalies, cancer, and neurodevelopmental and other childhood health problems. Males and females bring an equal number of chromosomes to their progeny, but their genomes may affect different aspects of reproduction. While the key male role principally ends at fertilization, there is growing experimental and human evidence that factors relating both to prefertilization and perifertilization exposure also play a role post fertilization. Some negative human epidemiologic findings reflect the fact that routinely gathered information usually generates detailed descriptions of maternal exposures and does not collect records regarding prefertilization paternal exposures. The absence of extensive human evidence should be interpreted as a deficiency in research rather than an absence of male-mediated adverse reproductive outcomes. More than 60 different compounds or industrial processes have been identified as increasing defects in human sperm and possibly increasing the risk to offspring from male-mediated exposures. Further research needs to include better characterizations of both maternal and paternal prefertilization and perifertilization exposures, in order to assess more accurately their relative effects. Pediatricians confronted with adverse pregnancy and antenatal health outcomes should obtain detailed information on relevant prefertilization exposures of both parents. PMID- 1521001 TI - A quality assurance program for teratogen information services. PMID- 1521002 TI - Does early exposure to maternal smoking affect future fertility in adult males? AB - Animal data suggest that prenatal exposure to certain tobacco smoke components such as nicotine may affect the development of the male gonadal axis, which may in turn affect future adult fertility. There are no previous epidemiologic studies on the potential effects of early (prenatal and childhood) exposure to maternal smoking on the reproductive system in adult male offspring. To investigate this question, we used data from a follow-up study of reproductive function and fertility among young adult sons of mothers who had participated in a randomized clinical trial of diethylstilbestrol use during pregnancy. We observed no significant effects of early exposure to maternal smoking on conventional semen characteristics, hormone levels (follicle stimulating hormone [FSH], luteinizing hormone [LH] and testosterone), urogenital abnormalities and diseases, or perceived infertility problems. Current active smoking by the men was, however, associated with a significant decrease in the percentage of sperm with normal morphology. PMID- 1521003 TI - Caffeine effects on meiotic maturation in hamster oocytes in vitro. AB - The effect of caffeine on meiotic maturation in cultured hamster oocytes was investigated. Meiotic status was scored from chromatin spreads of oocytes previously exposed to caffeine (0, 0.00017, 0.0017, 0.017, 0.17, 1.7, 2.4, 5.1, and 10.2 mM) for up to 20 h. While concentrations of caffeine less than 0.017 mM failed to affect significantly the onset of meiotic resumption, 0.0017 mM caffeine significantly decreased the proportion of oocytes progressing normally to telophase I-metaphase II, and concomitantly increased the proportion of both diploid MII and aneuploid oocytes. In addition, 0.17 to 10.2 mM caffeine induced a dose-dependent increase in the proportion of meiotically arrested oocytes, with less than 5% oocytes progressing normally through to the final stages of meiotic maturation at 10.2 mM caffeine. Taken together, these data show that caffeine at concentrations as low as 0.0017 to 0.017 mM interfere with progression of meiotic maturation, and that concentrations higher than 0.017 mM delay initiation of this process. Since caffeine peaks at 0.017 mM in the plasma of women following a cup of brewed coffee, we conclude that caffeine-induced perturbations of oocyte meiotic maturation may be responsible, at least in part, for the recently revealed correlation between caffeine intake and reduced fertility in women. PMID- 1521004 TI - Disruption of female rat vaginal cyclicity by daily treatment with imipramine. AB - Intact, adult female rats were injected for 21 days with 10 mg/kg of the tricyclic antidepressant imipramine. During this time, there was almost total suppression of reproductive cyclicity as indicated by the absence of vaginal proestrus and by the absence of sexual receptivity. However, there was no evidence for a permanent disturbance in the female reproductive system. When treatment with imipramine was terminated, vaginal cyclicity resumed within the next 2 to 8 days. The generality of the current findings to other antidepressants or to the human female is currently unknown. However, since human females are the primary consumers of antidepressants, caution should be exercised when females are given antidepressant therapy. PMID- 1521005 TI - Effects of oocyte exposure to local anesthetics on in vitro fertilization and embryo development in the mouse. AB - The effect on fertilization and development of local anesthetics routinely used during ultrasound-guided oocyte retrieval in women undergoing in vitro fertilization was examined in a mouse in vitro fertilization system. Mouse oocytes were exposed in vitro to lidocaine, chloroprocaine, and bupivacaine at concentrations of 0 (control), 0.01, 0.1, 1.0, 10.0, 100.0 micrograms/mL for 30 min, washed, and then inseminated. In vitro oocyte fertilization at 24 and 48 h and embryo development at 72 h were determined. Bupivacaine adversely affected mouse in vitro fertilization and embryo development only at the highest exposure concentration, 100 micrograms/mL, while lidocaine and chloroprocaine produced adverse effects at concentrations as low as 1.0 and 0.1 microgram/mL, respectively. Furthermore, an adverse dose-related effect on fertilization and embryo development was shown for lidocaine and chloroprocaine, but not for bupivacaine. These data demonstrate that the local anesthetics, lidocaine (L), chloroprocaine (C), and bupivacaine (B), adversely affect mouse in vitro fertilization and embryo development in the order of C greater than L greater than B. PMID- 1521006 TI - Genotoxic and embryotoxic effects of gonadotropin-hyperstimulated ovulation of murine oocytes, preimplantation embryos, and term fetuses. AB - Compared to spontaneous ovulation, gonadotropin-hyperstimulated ovulation (superovulation) in mice resulted in a fourfold increase in the number of preimplantation embryos 3 days post coitum, 50% of which died before term. Both in vitro development of embryos during the preimplantation period and transfer of morulae from superovulated females to pseudopregnant untreated foster mothers indicate that the prenatal loss occurring shortly before implantation up to term is due to maternal factors rather than to direct hormonal effects on oocytes or early embryos. Indeed, no genotoxic events could be observed in 4-cell to blastocyst stage embryos from superovulated female mice as revealed by the chromosomal aberration test and the sister chromatid exchange assay. Chromosome analysis of the pronuclei from mouse zygotes showed an increased rate of aberrations in oocyte-derived nuclei after superovulation in comparison to spontaneous ovulation. The present data suggest that aberrant murine oocytes may be fertilized, but they do not survive the first cleavage stages. The result is discussed with respect to the high incidence of chromosomal abnormalities found in human oocytes after gonadotropin-hyperstimulated ovulation. PMID- 1521007 TI - Alterations in hypothalamic and pituitary hormone levels induced by neonatal treatment of female mice with diethylstilbestrol. AB - Neonatal female mice of the NMRI strain were treated with the synthetic estrogen diethylstilbestrol (DES), 5 micrograms daily for the first 5 days after birth, or with vehicle only. Levels of LH and FSH (pituitary and serum) and LHRH (hypothalamus) were measured by radioimmunoassay (RIA) in 6- to 56-day-old females with 6- to 7-day intervals. Compared to controls, DES-treated females had low levels of LH on days 6, 12, and 21 in the pituitary, and on days 6 and 12 in serum; increased LH levels were seen in both the pituitary and serum on day 42. The FSH levels of DES-treated females were decreased on days 6 and 12 in the pituitary and on day 6 in serum; an increased FSH content occurred on day 21 in the pituitary. In the preoptic area and basal hypothalamus of DES-treated females, levels of LHRH were increased on day 21 and decreased on day 42. On day 56, the serum levels of FSH and LH and the hypothalamic content of LHRH were similar in controls and DES females. A second study including both synthetic and natural estrogen was performed in 12-day-old females. Treatment with 10(-2) micrograms DES or lower doses or 5 micrograms estradiol-17 beta (E2) on days 1 to 5 after birth had no depressive effect on serum LH. The hypothalamic-pituitary ovarian feedback system reacted similarly to ovariectomy and E2 challenge in 15 day-old control and DES-treated females. DES-treated 56-day-old females had a reduced LH response to ovariectomy but increased response to exogenous E2 compared to controls. These results show that neonatal treatment with DES has pronounced effects on the hypothalamic-pituitary system in the developing female mouse, which may be of importance for the altered ovarian function in these females as adults. PMID- 1521008 TI - Reproductive toxicity of theobromine and cocoa extract in male rats. AB - The toxicities of theobromine and cocoa extract on the reproductive tract of male rats were compared in the present study. A cocoa powder extract containing 117 mg theobromine/g extract was prepared using 85% boiling methanol. Sprague-Dawley rats were weighed and dosed daily for 31 days with vehicle, 250 mg/kg theobromine, 2.14 g/kg cocoa extract (117 mg theobromine/g extract), or 0.43 g/kg cocoa extract by oral gavage. The animals were sacrificed on day 32. One testis and epididymis were removed and weighed. The epididymis was saved for the determination of epididymal sperm reserves. The remaining testis was fixed by whole body glutaraldehyde perfusion and processed for morphologic examination. A decrease in body weight gain and epididymal weights were observed in theobromine and high-dose cocoa-extract-treated groups. Theobromine and high-dose cocoa extract caused vacuolation within the Sertoli cell, abnormally shaped spermatids, and failed release of late spermatids in treated animals. Most of the vacuolations were found in the earlier and middle stage seminiferous tubules (stages I to VIII). However, the frequency of some parameters of testis alterations were significantly lower in the high-dose cocoa-extract-treated group compared to the theobromine-treated group. These data demonstrate the ability of a cocoa extract containing theobromine to alter testis structure in a similar pattern but with reduced intensity compared to that observed after oral exposure to pure theobromine. PMID- 1521009 TI - Testicular toxicity of methylmercury: analysis of cellular distribution pattern at different stages of the seminiferous epithelium. AB - Stage-specific distribution of methylmercury (MM) and spermatogenic changes were analyzed in rats administered 5 or 10 micrograms MM/kg, ip, daily for 15, 30, 60, and 90 days. MM deposition, as grain number/cm2 was noted in basal portions at later stages on day 15, which increased gradually by day 90. MM deposition was in the order of stages IV, VII, XIV, IX, being higher in adluminal portions on days 30 and 60. MM-enriched cytoplasmic masses leaked out through disintegrated tubular membrane on days 60 and 90. Epithelial damage, at stages late XIV through IV, V through VI, VII through VIII, XIII through mid-XIV, and IX through XII, accorded with the gradual deposition of MM. As profound cell death occurred between zygotenes to pachytenes and dividing spermatocytes to step 1 spermatids, the spermatids were conspicuously decreased at later times. It is possible that MM distorts the barrier system at stages IX through XII, gets distributed within the tubule, and hence may pose a direct or Sertoli cell mediated effect at stages XII through early XIV in a dose-duration-MM burden related manner. PMID- 1521010 TI - Quinone reductase activity in the first trimester placenta: effect of cigarette smoking and polycyclic aromatic hydrocarbons. AB - Quinone reductase (QR) is considered a major protective enzyme against cancer in the organism. In this study, the activity of QR was measured in first trimester placental tissue using colorimetric techniques. There were no significant differences between the mean enzyme activity of women who smoked more than 20 cigarettes per day during pregnancy and of nonsmokers (0.50 +/- 0.09 compared with 0.51 +/- 0.15 mumol/mg protein/10 min, respectively). Among the polycyclic aromatic hydrocarbons (PAH) studied, dimethyl benzanthracene (DMBA) increased QR activity in a dose-dependent manner in the first trimester placental explants at the 10- to 100-microM range after 6 h of incubation (440% increase) with the highest concentration. The effect of other PAH of different potency added at 50 microM concentrations showed that benz(a)anthracene (BA), dibenzo(a,h)anthracene (DBHA), dibenzo(a,c)anthracene (DBCA), or chrysene (CH) caused a significant 2- to 3-fold increase in the enzymatic activity after 6 h of incubation. At 24 h 50 microM DBCA effect was also stimulatory, while the 10-microM DMBA effect almost reached statistical significance. However, no differences were encountered in the response of placental tissues to PAH between cigarette smokers and nonsmokers at 6 and 24 h. The present data indicate that placental QR activity is increased by exposure to PAH in vitro, but it does not appear to be affected by in vivo exposure to cigarette smoking. Thus, the early placenta appears to have a significant potential to inactivate carcinogens/mutagens locally, thereby limiting their transfer to the embryo. PMID- 1521011 TI - Embryotoxicity of 25 psychotropic drugs: a study using CHEST. AB - Twenty five psychotropic drugs were ranked according to the embryotoxicity dose ranges estimated by the Chick Embryotoxicity Screening Test (CHEST). The chick results were compared with some data for common laboratory mammals. In 17 psychotropic drugs a deleterious dose-dependent effect upon the embryonic cardiovascular system was disclosed, terminating in immediate cardiac arrest. PMID- 1521012 TI - [The role of genetic factors in the development of ischemic heart disease in patients with chronic nonspecific lung diseases]. AB - The investigations of the clinico-genetic factors in chronic bronchitis sufferers with phenotype A revealed atherogenic changes in lipoprotein spectrum and suppression of plasma fibrinolytic activity. It is suggested that chronic staphylococcal infection may contribute to high coagulating blood properties in relevant patients. PMID- 1521013 TI - [Clinico-morphological characteristics of intrahepatic cholestasis in hepatitis A and delta infection]. AB - Clinical and morphological characteristics were studied for a course of acute viral hepatitis A and delta with long-term cholestatic syndrome in asymptomatic carriers of HBsAg. 149 patients with moderate disease were examined, 53 of them had long-standing cholestasis syndrome. 96 viral hepatitis patients free of cholestasis served control. It is believed that the emergence of long-term intrahepatic cholestasis may be due to the following mechanisms of sinusoid lumina as a result of a drastic enlargement of multinuclear hepatocytes, hyperplasia and hypertrophy of Kupffer's cells. impaired binding of bilirubin in zone III of hepatic acinus. In cholestatic form of hepatitis A there occurs more pronounced reduction of sinusoid volume compared to other variants of viral hepatitis run. PMID- 1521014 TI - [Vertebrogenic lesions of the peripheral nervous system in pregnant women and puerperae]. AB - Neurologic appearance of spinal osteochondrosis was assessed in 112 pregnant women and puerperae . In 75 females osteochondrosis involved the lumbosacral and in 37 ones cervical-thoracic regions. In the majority of the patients (79%) vertebrogenic lesions manifested with reflex syndromes. Provoking factors and the clinical pattern of the disease are considered with special emphasis on the role of pregnancy and labour as promoters of pain recurrences and the onset of new symptoms in women with neurological picture of osteochondrosis. PMID- 1521015 TI - [Diagnosis of pigmentary liver diseases]. PMID- 1521016 TI - [Doppler echography of renal blood vessels]. PMID- 1521017 TI - [Clinico-echocardiographic characteristics of the course of myocardial infarction in heart rupture]. PMID- 1521018 TI - [Clinico-echocardiographic picture of organic insufficiency of the tricuspid valve]. PMID- 1521019 TI - [New approach to clinical description of the neoplastic process based on the system of anatomical staging of malignant neoplasms]. PMID- 1521020 TI - [Cancer cells in peripheral lymph and blood and their effect on the morbidity of patients with breast cancer]. PMID- 1521021 TI - [Clinical course and outcome of acute hepatitis B in relation to the markers of the E system]. PMID- 1521022 TI - [Effect of isosorbide dinitrate on the blood circulation system in patients with ischemic heart disease]. PMID- 1521023 TI - [Gastrointestinal microflora in surgical treatment of peptic ulcer]. PMID- 1521025 TI - [Medical aspects of ecology]. PMID- 1521024 TI - [Calcium antagonists in the treatment of cerebrovascular diseases]. PMID- 1521026 TI - [A method of anesthesiological protection during operations on the liver]. PMID- 1521027 TI - [Therapeutic tactics in multisegmental fractures of the upper and lower extremities]. PMID- 1521028 TI - [Diffuse sarcoma of the pia mater]. PMID- 1521029 TI - [Clinico-morphological characteristics of focal myocardial damage in myocarditis and myocardial dystrophy]. PMID- 1521030 TI - [Effect of psychopathological disorders in patients with unstable stenocardia on serum lipids and the indicators of lipid peroxidation]. AB - A total of 193 males suffering from unstable angina pectoris (UAP) were examined against 20 control subjects with stable angina pectoris (SAP) for the serum levels of lipids and activity of lipid peroxidation. The parameters studied varied between the groups. 152 UAP patients exhibited psychopathological disturbances, mainly agitated melancholia. These patients (78.8%) were noticed to have atherogenic shifts in serum lipids and lipid peroxidation products levels increased as compared to those without psychoemotional problems. It was found that in UAP psychopathologic disturbances contribute to the progress of coronary insufficiency this justifying the use of psychotherapy in combination with drugs in UAP patients. PMID- 1521031 TI - Leadership: what AHNA means to me. PMID- 1521032 TI - Increased cotinine elimination and cotinine-N-oxide formation by phenobarbital induction in rat and mouse. AB - The metabolic fate of cotinine, the major metabolite of nicotine, was studied in phenobarbital-induced and non-induced isolated perfused rat lung and liver and in isolated hepatocytes of rats and mice. The non-induced lung tissue showed low cotinine metabolizing capacity while the perfused liver was approximately four times more active. After phenobarbital pretreatment the metabolism of cotinine was increased eight-fold in the intact liver. A substantial increase in cotinine metabolism was also found in isolated hepatocytes from PB-induced rats and in cultured mouse hepatocytes grown in a medium supplemented with PB. This was paralleled by an increased formation of cotinine-N-oxide which could be inhibited by 100 microM metyrapone. In contrast, the pulmonary elimination of cotinine was not affected by PB. A dominant role of primary N-oxidation of nicotine compared to C-oxidation was apparent in non-induced rat liver. After PB treatment the rate of nicotine-N'-oxide formation dropped markedly while the cotinine related pathways were increased causing an inversion of the N- to C-oxidation ratio. In the lung, cotinine formation was the preferred metabolic pathway of nicotine already in non-induced organs. The pattern of nicotine metabolites was not altered by PB induction. In conscious PB-induced rats receiving nicotine orally or intravenously, 3'-hydroxycotinine was found as the main urinary metabolite of nicotine while only a small fraction was excreted as cotinine-N-oxide. This discrepancy between the profile of nicotine metabolites in perfused liver and lung and in the urine in vivo indicates that extrahepatic organs other than the lung may be important sites of cotinine metabolism. PMID- 1521033 TI - Effects of nicotine receptor agonists on acetylcholine release from the isolated motor nerve, small intestine and trachea of rats and guinea-pigs. AB - The effects of nicotine receptor agonists on the release of [3H]acetylcholine from the phrenic nerve, the small intestine and the trachea were investigated to characterize neuronal nicotine receptors within the peripheral nervous system. Contraction of the indirectly-stimulated hemidiaphragm was recorded to investigate desensitization of the postsynaptic muscular nicotine receptors. Nicotine, cytisine, 1,1-dimethyl-4-phenylpiperazinium and 2-(4-aminophenyl)-ethyl trimethyl-ammoniumiodide caused a concentration-dependent (0.1-30 microM) increase in evoked [3H]acetylcholine release from the phrenic nerve, whereby bell shaped concentration-response curves were obtained. The rank order of decreasing potency was: nicotine greater than cytisine greater than 1,1-dimethyl-4 phenylpiperazinium greater than 2-(4-aminophenyl)-ethyl-trimethyl-ammoniumiodide. The presynaptic effects of nicotine depended strongly on the exposure time: facilitation occurred after a short 20 s exposure and inhibition after a 3 min exposure, whereas nicotine no longer affected evoked [3H]acetylcholine release after a 15 min exposure. Pre-exposure (40 min) of the phrenic nerve to 0.3 microM nicotine prevented any subsequent modulatory effect of a high nicotine concentration. In contrast, the contraction of the indirectly-stimulated hemidiaphragm remained unaffected in the presence of 0.3-30 microM nicotine, but a concentration of 1 mM nicotine abolished skeletal muscle contraction. Nicotine (10 microM) produced a substantial release of [3H]acetylcholine in the small intestine but not in the isolated trachea. The present experiments show presynaptic nicotine receptors at the phrenic nerve, which, under appropriate conditions, can mediate facilitation of evoked transmitter release. These neuronal receptors appear more sensitive to desensitizing conditions than the postsynaptic muscular nicotine receptors.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1521034 TI - Effects of cigarette smoking or ingestion of nicotine on platelet 5 hydroxytryptamine (5-HT) levels in smokers and non-smokers. AB - Platelets of healthy smokers and non-smokers were prepared and their content of 5 hydroxytryptamine was determined by HPLC with electrochemical detection. Platelet 5-HT levels in smokers (728 +/- 156 pmol per 10(8) platelets, mean +/- SEM, n = 9) were significantly higher than those in non-smokers (353 +/- 156 pmol per 10(8) platelets, n = 11). Smoking of a single cigarette caused a transient increase in platelet 5-HT levels by about 350% in non-smokers, but had no additional effect in smokers. Similarly, chewing of nicotine gum (4-8 mg nicotine) resulted in a transient increase in platelet 5-HT by about 100% in non smokers, but not in smokers. In conclusion, smoking of cigarettes can cause an increase in platelet 5-HT, most likely via an enhanced supply of 5-HT from enterochromaffin cells which can be stimulated via nicotine receptors. PMID- 1521035 TI - Lack of effect of topically applied nicotine on pial arteriole diameter and blood brain barrier integrity in the cat. AB - In the present study, the vasomotor effects of nicotine, its interaction with local chemical factors and norepinephrine, and its effects on the permeability of the blood-brain barrier (BBB) were investigated. Using perivascular microapplication, 10(-6) M nicotine was found not to exert a vasomotor effect by itself or to modify the vasodilating effect of an increase in perivascular H+, K+ and adenosine concentration. The constrictor effect of a decrease in H+, K+ or an increase in norepinephrine concentration in the perivascular space was also not altered by 10(-6) M nicotine, indicating a lack of interaction between nicotine and the compounds tested. Using cortical superfusion and intravital fluorescence microscopy nicotine (10(-7) to 10(-3) M) was also found not to affect the diameter of pial arteries during superfusion periods of 30 min each. The integrity of BBB could be demonstrated in time-matched solvent controls over 3 h using intravenously-infused FITC-labelled dextran (MW 70,000) as tracer. During cortical superfusion with 10(-7) to 10(-5) M nicotine the permeability of the BBB was not increased compared with the time-matched controls. However, during superfusion with 10(-4) and 10(-3) M nicotine, tracer extravasation could be quantified by computer-aided image analysis. The extravasation index (EI) increased by up to eight times. These data indicate that only toxic concentrations of nicotine increase BBB permeability to FITC-dextran 70,000. PMID- 1521036 TI - Effect of nicotine on mRNA levels encoding opioid peptides, vasopressin and alpha 3 nicotinic receptor subunit in the rat. AB - The effect of acute and chronic nicotine treatment of rats on the mRNA levels coding for the three opioid peptide precursors, for provasopressin and for the alpha 3 subunit of nicotinic receptors in brain, pituitary and/or adrenal medulla of rats was investigated. Nicotine was found to increase the levels of proenkephalin mRNA in the adrenal medulla, but did not affect the levels of PENK mRNA in striatum, hypothalamus and hippocampus. The mRNA levels of prodynorphin were increased together with that of provasopressin in the hypothalamus after nicotine, whereas the prodynorphin mRNA levels in the hippocampus and the striatum remained unchanged. Nicotine treatment resulted in an increase in the pro-opiomelanocortin mRNA levels in the anterior pituitary and in a decrease in the intermediate pituitary, but did not change the levels of pro-opiomelanocortin mRNA in the hypothalamus. The levels of mRNA coding for the alpha 3 subunit of nicotinic receptors in the hypothalamus and the adrenal medulla remained unchanged. The increase in the prodynorphin and provasopressin mRNA levels in the hypothalamus was most pronounced 1 day after s.c. application of two doses of 0.4 mg/kg nicotine (about 100% above control). A smaller increase in mRNA concentrations (about 30%) was found after tonic infusion of the drug for 4 days (4 mg/kg per day), whereas no change was observed after tonic infusion of nicotine for 7 and 14 days indicating the development of complete tolerance.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1521037 TI - Differential effects of acute and chronic nicotine treatment on MPTP-(1-methyl-4 phenyl-1,2,3,6-tetrahydropyridine) induced degeneration of nigrostriatal dopamine neurons in the black mouse. AB - Evidence exists for a negative correlation between Parkinson's disease and smoking. The present and previous studies indicate that nicotine treatment can markedly alter the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced neurotoxicity in the black mouse based on biochemical determinations of dopamine (DA), 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) levels in neostriatum and substantia nigra 2 weeks after MPTP injection. Acute intermittent treatment with (-)nicotine starting 10 min before the MPTP injection partly protected against MPTP-induced neurotoxicity in the neostriatum and substantia nigra. Also, a partial protection was observed in the substantia nigra when (-)nicotine was given together with MPTP in an acute intermittent treatment schedule. Conversely, chronic infusion of (-)nicotine via minipumps produced a dose-related enhancement of MPTP-induced DA neurotoxicity in the neostriatum. It is suggested that the protective activity of nicotine in the MPTP model is related to a blockade of MPP+ uptake into the DA cells via increased DA release. Conversely, the nicotine enhancement of MPTP-induced DA toxicity is suggested to be caused by a failure of the nicotinic cholinoceptors to desensitize to the chronic (-)nicotine exposure, leading to increased chronic influx of Na+ and Ca2+ ions via the ion channels of the nicotinic cholinoceptors located on the DA neurons with associated increased Ca ion toxicity and increased energy demands. PMID- 1521038 TI - A new role for nicotine: selective inhibition of thromboxane formation by direct interaction with thromboxane synthase in human promyelocytic leukaemia cells differentiating into macrophages. AB - Thromboxane, one of the major oxygenated arachidonic acid metabolites of human macrophages, is the most potent vasoconstricting and proaggregatory molecule known. In addition, thromboxane has been shown to be related to host defence mechanisms. We studied the effects of nicotine and its major metabolites on thromboxane formation using cultured macrophage-like cells (HL-60), microsomal assays and purified thromboxane synthase. In intact cells, nicotine, cotinine and methylnicotine at submicromolar concentrations inhibited the rate of conversion of both arachidonic acid and the unstable endoperoxide prostaglandin H2 into thromboxane but not into other eicosanoids. This indicates that nicotine selectively inhibits thromboxane synthase at concentrations that are readily observed in the circulation of smokers. Microsomal assays revealed that nicotine decreased the maximal velocity of thromboxane synthase without affecting the apparent affinity of the enzyme for its substrate. In contrast, no effect of nicotine on kinetic parameters of prostaglandin H synthase or prostacyclin synthase could be observed. Difference spectra, using purified thromboxane synthase, revealed that nicotine directly interacts with the enzyme, presumably by binding the nitrogen of the nicotine ring structure to the iron of the cytochrome P-450 component of thromboxane synthase. PMID- 1521039 TI - Nicotine increases ciliary beat frequency by a direct effect on respiratory cilia. AB - We studied the direct effects of nicotine on the ciliary beat frequency (CBF) undisturbed by interference from mucus secretion by using epithelial strips from ferret tracheae which contain no goblet cells and, because the glands were left behind in the submucosa, no gland tissue either. Strips were studied in a chamber perfused with medium M-199 at 37 degrees C at a perfusion rate of 1.6 ml min-1 using a perfusion pump (Braun, Melsungen). CBF was determined photometrically, the signal being subjected to a fast Fourier transformation. We measured CBF continuously for 10 min (5 min with and 5 min without perfusion). Under baseline conditions without nicotine, it decreased from 23.4 +/- 0.8 to 22.2 +/- 0.5 Hz during perfusion and increased from 22.0 +/- 0.8 to 23.3 +/- 0.8 Hz during the subsequent period without perfusion. Nicotine increased CBF transiently, i.e., the effect was demonstrable only during perfusion, being strongest during the first 3 min of perfusion. At 10(-5) M, the increase in CBF was significant only during the 3rd minute, but at 10(-4) and 10(-3) M, CBF was elevated significantly throughout most of the perfusion period compared with control tissues perfused with medium M-199 only. Thus, at 2 min, CBF was 22.8 +/- 0.6 (mean +/- SE) in tissues perfused with medium M-199 only but was 24.3 +/- 0.8 Hz (NS, Student's unpaired t-test), 26.6 +/- 0.5 Hz (P = 0.001), and 26.8 +/- 1.2 Hz (P = 0.01) in tissues perfused with 10(-5), 10(-4), and 10(-3) M nicotine (dissolved in medium M-199), respectively.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1521040 TI - Smoking influences the atherogenic potential of low-density lipoprotein. AB - The possible influence of smoking on the low-density lipoprotein (LDL) and its biological activity was investigated. Plasma LDL was prepared from healthy male smokers and nonsmokers, and oxidized with Cu (II) as prooxidant. Oxidized LDL from smokers generated significantly more lipid peroxidation products, so-called thiobarbituric acid reactive substances (TBARS), when compared to oxidized nonsmoker LDL. Analysis of vitamin E levels in LDL obtained from both smokers and nonsmokers revealed that the vitamin E content of smoker LDL was significantly less than that of nonsmoker LDL. The amounts of cholesteryl esters formed in cultured P388. D.1 macrophages were greater in the presence of smoker LDL than with nonsmoker LDL. The data suggest that some of the proatherogenic effects of smoking may be related to oxidative modification of LDL and alteration of its biological activity. PMID- 1521041 TI - Alpha 1-proteinase inhibitor and mucus proteinase inhibitor in human lung emphysema. AB - The role of the antiproteases alpha 1-proteinase inhibitor (alpha 1PI) and mucus proteinase inhibitor (MPI) in human lung emphysema was investigated by measuring their amount and functional activity against trypsin, leukocyte elastase, and pancreatic elastase in the bronchoalveolar lavage fluid (BALF). In addition, leukocyte elastase was quantified in the lavage samples by measuring the concentration of the elastase-alpha 1PI-complex. The study population consisted of 38 patients (5 nonsmokers, 8 former smokers, 25 smokers) with acquired emphysema (i.e., emphysema which is not caused by alpha 1PI deficiency), and 44 individuals (16 nonsmokers, 8 former smokers, 20 smokers) without emphysema. No differences were found between patients with and without emphysema in the activities of alpha 1PI and MPI, or in the concentration of alpha 1PI. The concentration of MPI was significantly higher in the BALF of patients with emphysema than in that of patients without emphysema (p = 0.025). A significantly higher concentration of elastase-alpha 1PI complex was found in patients with emphysema than in those without emphysema (p = 0.041). This finding could reflect the higher proteinase burden to which patients with emphysema are exposed. The increase of MPI in lavage fluid of patients with emphysema seems to be the result of increased production in emphysematous lungs. However, it remains unclear why patients develop emphysema while showing an increased content of MPI. PMID- 1521042 TI - Volatile N-nitrosamines in mainstream cigarette smoke: occurrence and formation. AB - Analytical data is presented for the occurrence of the three major volatile N nitrosamines in cigarette tobacco and mainstream smoke, namely N nitrosodimethylamine (NDMA),- N-nitrosoethylmethylamine (NEMA) and N nitrosopyrrolidine (NPYR) as well as for the occurrence of the corresponding precursor amines and non-volatile N-nitrosamino acids in tobacco. Experimental studies using the C20 reference cigarette show that NPYR present in mainstream smoke results from direct transfer of preformed NPYR (ca. 1.5%), decarboxylation of N-nitrosoproline in tobacco (ca. 10%), pyrolytic nitrosation of pyrrolidine in tobacco (ca. 37%) and concerted decarboxylation/nitrosation of proline (ca. 52%) during tobacco pyrolysis. PMID- 1521043 TI - Tobacco-specific nitrosamines--metabolism and biological monitoring of exposure to tobacco products. AB - Tobacco-specific nitrosamines are derived from nicotine and related tobacco alkaloids and can be detected in tobacco products as well as in mainstream and sidestream smoke. Two of them, N-nitrosonornicotine and 4-(methylnitrosamino)-1 (3-pyridyl)-1-butanone, are strong carcinogens in laboratory animals. Because of its organospecificity for the lung, the latter is considered to be a causative factor in tobacco-related human lung cancer. Upon metabolic activation both nitrosamines give rise to a common reactive intermediate binding to macromolecules such as DNA and haemoglobin and hydrolysing to 4-hydroxy-1-(3 pyridyl)-1-butanone. Because of easy access to large quantities of haemoglobin from blood samples, it is most suitable for biomonitoring human exposure to tobacco-specific nitrosamines. A highly sensitive analytical method for determination of femtogram amounts of 4-hydroxy-1-(3-pyridyl)-1-butanone provides an approach to assess individual exposure to active and passive smoking. PMID- 1521044 TI - Determinants of a genotoxic effect of 4-(methylnitrosamino)-1-(3-pyridyl)-1 butanone (NNK) in human diploid fibroblasts. AB - The induction of micronuclei was studied in human diploid fibroblasts incubated in the presence of the tobacco-specific nitrosamine NNK. We used four fibroblast strains having a high capacity of O6-alkylguanine DNA alkyltransferase (13.0-23.3 pmol O6-methylguanine repaired per 8 x 10(6) cells) and four strains that showed no detectable repair capacity. Incubation with NNK doubled the frequency of micronuclei in repair-deficient cells but failed to evoke any effect in the proficient cell strains. Control experiments were performed with the direct methylating agent MNNG and in the presence of inhibitors of either metabolic activation or alkyltransferase. The results showed that the genotoxicity of NNK is dependent on the relationship between its metabolic activation and the constitutive DNA repair. This supports earlier findings that low constitutive levels of O6-alkylguanine DNA alkyltransferase may increase susceptibility to lung cancer after exposure to DNA methylating agents. PMID- 1521045 TI - Systemic genotoxic effects of tobacco-related nitrosamines following oral and inhalational administration to Sprague-Dawley rats. AB - An ex vivo model to detect nonspecific DNA damage in different rat tissues has been developed and employed to study systemic properties of tobacco-specific N nitrosamines. One hour after treatment of rats with the carcinogens, primary, intact cells were isolated from various organs. Viability of the cells was monitored by trypan blue exclusion. Genotoxicity was determined by alkaline elution, in situ nick translation or microgel electrophoresis. We found that oral application of 4-(N-methyl-N-nitrosamino)-1-(3-pyridyl)-1-butanone (NNK) induces genotoxic effects in the liver (3.125-50 mg/kg), whereas N-nitrosonornicotine (NNN) is only moderately active (50-100 mg/kg). Furthermore, oral administration of NNK, NNN, and of N-nitrosodimethylamine (NDMA), induces DNA damage in the nasal cavity. In peripheral blood lymphocytes genotoxicity of NDMA (less than 2 mg/kg), but not of NNK (50 mg/kg), was observed. NDMA and NNK are just as genotoxic in the liver when administered by inhalation as orally (effective doses: 0.1-1 and 50 mg/kg, respectively). For human cancer, these results indicate that in addition to the susceptibilities in local organs (oral cavity after snuff dipping and lung after tobacco smoke inhalation), these nitrosamines also pose a risk systemically for more remote organs. PMID- 1521047 TI - Acute ventilation-perfusion mismatching resulting from inhalative smoking of the first cigarette in the morning. AB - The effect of the first cigarette in the morning on the airway resistance (Raw) which can be measured by body-plethysmography was investigated in 70 inhaling cigarette smokers. The test population showed a significant (P less than 0.0005) fall in Raw 8 min after smoking. A further study (n = 16) showed that the fall in Raw was most likely to be attributable to a decrease in the trapped air. The effect of the first cigarette in the morning on the arterial blood gases and on the alveolar-arterial oxygen difference P(A-a)O2 and carbon dioxide difference P(A-a)CO2 was investigated in 12 inhaling cigarette smokers. Smoking gave rise to a significant (P less than 0.0005) fall in the partial pressure of oxygen (PaO2) with compensatory overventilation. At the same time, the P(A-a)O2 and the P(A a)CO2 increased significantly (P less than 0.01 and P less than 0.05, respectively). This effect could be observed for up to 24 min after smoking. In addition, the flow of blood in the pulmonary capillaries was measured in 28 test subjects with the nitrous oxide method (QN2O) before, and 18-22 min after, smoking the first cigarette in the morning. After smoking, there was a significant (P less than 0.0005) fall in the QN2O by an average of 11.3%. The decrease in the Raw, the fall in the PaO2 with compensatory overventilation, the increase in P(A-a)O2 and P(A-a)CO2 and the decrease in the QN2O are interpreted as manifestations of pronounced acute ventilation-perfusion mismatching induced by smoking. PMID- 1521046 TI - Tobacco and alcohol and the risk of head and neck cancer. AB - We carried out two case-control studies on the relative risk of head and neck cancer in association with tobacco and alcohol consumption. The first study carried out at the ENT Department of the University hospitals of Heidelberg and Giessen (FRG) comprised 200 male patients with squamous cell cancer of the head and neck and 800 control subjects matched for sex, age, and residential area (1:4 matching design). Of the tumour patients, 4.5% had never smoked, in contrast to 29.5% of the control group. The average tobacco and alcohol consumption of the patients was approximately twice as high as in the control subjects. The highest alcohol and tobacco consumption was observed in patients suffering from oropharyngeal cancer. Tobacco and alcohol increased the risk of head and neck cancer in a dose-dependent fashion and acted as independent risk factors. In heavy smokers (greater than 60 pack-years) a relative risk of 23.4 (alcohol adjusted) was calculated. Combined alcohol and tobacco consumption showed a synergistic effect. The risk ratio increased more in a multiplicative than in an additive manner. Oral and laryngeal cancer were associated with the highest tobacco-associated risk values. The highest ethanol-associated risk values were associated with oropharyngeal and laryngeal cancer. The second study was carried out at the ENT Department of the University of Heidelberg on 164 males with squamous cell carcinoma of the larynx and 656 control subjects matched for sex, age and residential area (1:4 matching design). Of the cases, 4.2% had never smoked, compared with 28.5% of the control subjects.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1521048 TI - Smoking behaviour and increase in nicotine and carboxyhaemoglobin in venous blood. AB - The connection between smoking behaviour (number of puffs, puff volume, depth of inhalation, duration of inhalation) and the increase in both nicotine and carboxyhaemoglobin (COHb) in venous blood was investigated with methods developed especially for measurement of the puff volume, the depth of inhalation, and the duration of inhalation in 28 inhaling cigarette smokers. A significant correlation could be demonstrated between the smoking parameters and the nicotine and carboxyhaemoglobin increase. The weighting obtained shows that the number of puffs is the most important parameter affecting the increase in nicotine, whereas the depth of inhalation and the puff volume are of much less relevance. The duration of inhalation does not affect the nicotine level. A significant increase in nicotine cannot be attained in non-inhalative smoking of cigarettes with an acid mainstream smoke (n = 14). The increase in COHb is most affected by the puff volume, and slightly less by the number of puffs and the depth of inhalation. The duration of inhalation does not affect the COHb level. PMID- 1521049 TI - The contributions of cigarette yield, consumption, inhalation and puffing behaviour to the prediction of smoke exposure. AB - The overall predictability of smoke exposure indicators and the importance of different influencing factors were assessed in a cross-sectional study (n = 144), using multiple linear regression and bivariate correlation analyses. Respiratory CO, and plasma nicotine and cotinine concentrations were measured before and after smoking, for lip or holder smoking, and natural or standardized (30 puffs) puffing. The prediction of smoke exposure measures varied considerably across sampling times, smoking conditions, and dependent variables. The variance of plasma cotinine and nicotine were predictable to a considerable extent (30%; 19 41%) by cigarette yield, consumption and self-reported inhalation, whereas respiratory CO was less predictable (15-27%). Generally, consumption was the most important predictor, surpassed by nicotine yield for post-smoking plasma nicotine. Smoke exposure from a single smoking period could be predicted to a variable degree (CO, 11-42%; nicotine, 33-54%) by a subset of smoker's sex, cigarette yield, self-reported inhalation and puffing characteristics. The highest prediction was found under standardized smoking conditions (30 puffs through a holder), the lowest under natural smoking conditions. The best subset of predictors, especially with respect to puffing parameters, was found to vary considerably across smoking conditions and dependent variables. PMID- 1521051 TI - PREP: gaining momentum or slowing down? PMID- 1521050 TI - Uptake of tobacco smoke constituents on exposure to environmental tobacco smoke (ETS). AB - For the purpose of risk evaluation, passive smoking is frequently regarded as low dose cigarette smoking. However, since the physical, chemical and biological properties of mainstream smoke (MS), which is inhaled by the smoker and environmental tobacco smoke (ETS), which is breathed by the passive smoker are quite different, risk extrapolation from active smoking to passive smoking is of doubtful value. In a series of experimental exposure studies we compared the uptake of tobacco smoke constituents by active and passive smoking. The results show that biomarkers which were found to be elevated after experimental ETS exposure, such as nicotine and cotinine in plasma and urine as well as thioethers in urine, indicate gas-phase exposure in passive smokers, but particle-phase exposure in active smokers. Biomarkers which should indicate the uptake of particle-bound, genotoxic substances with ETS, such as urinary mutagenicity, metabolites of polycyclic aromatic hydrocarbons (PAH) and DNA adducts, were not found to be elevated even after extremely high ETS exposure. From these results we conclude that a risk evaluation for passive smoking on the basis of dosimetric data is currently not possible. PMID- 1521052 TI - The Health of the Nation: how should nurses respond? PMID- 1521053 TI - Long-term effects of cancer on children and their families. AB - An increasing number of children now survive malignancies, which has implications for nursing practice in caring for long-term survivors and their families. This article will examine the physical, psychological and social consequences of surviving childhood cancer and will suggest how nurses can meet the needs of long term survivors. PMID- 1521054 TI - Using a monitored dosage system. AB - Traditional methods of administering medicines in nursing and residential homes have varied in standard throughout the UK. Monitored dosage systems have the potential to remedy this by making drug administration easier, safer, more hygienic and quicker. This article describes the use of one such system. PMID- 1521055 TI - Management of lymphoedema: a community-based approach. AB - Lymphoedema causes considerable physical, emotional and social problems. This article describes the establishment of a community lymphoedema service in one district health authority. The proposal won the Queen's Nursing Institute Innovation Award in 1991. A second article will review the first year of the clinical service. PMID- 1521056 TI - Safety from sharps. AB - Needlestick and sharps injuries are responsible for 35% of hospital injuries to staff. Despite this, there has been little effort in the past to reduce potential hazards. Nurses and other healthcare personnel must be made aware of the risks so that they can improve their practice. PMID- 1521057 TI - Care of a child with hypospadias: ethical issues in practice. PMID- 1521058 TI - Education and staffing in the ICU: past, present and future. PMID- 1521059 TI - What is a registered nurse? PMID- 1521060 TI - A child's right to die: who should decide? AB - When deciding whether to treat children, quality of life is as important as quantity of life. There is some confusion over who has the right to make these treatment decisions. Healthcare professionals are often not the most appropriate decision-makers. PMID- 1521061 TI - How to choose the right applicant: 2. AB - Deciding which candidate to appoint requires considerable discussion and skill. Giving feedback to the unsuccessful candidate should be carefully considered. PMID- 1521062 TI - Nurse information systems: how to gain competitive advantage. AB - This article considers how nurse information systems can make provider units more competitive by supporting a quality-based strategy, and examines the organizational characteristics necessary for success. PMID- 1521063 TI - Interpersonal skills training in Brunei. AB - This article describes an interpersonal skills training workshop set up in Brunei, Darussalam. It identifies important issues in the facilitation of such workshops, which have relevance for interpersonal skills training in a range of cultures. PMID- 1521064 TI - Changes in the amphibian antibody repertoire are correlated with metamorphosis and not with age or size. AB - Tadpole and adult Xenopus, manipulated to be of comparable size, exhibited stage specific antibody expression. The production of adult-type higher-affinity anti DNP antibodies proved to be independent of the age and size of the individual and is concomitant with the completion of metamorphosis. The appearance of new antibody specificities at such a time suggests that their expression occurs with the cell turnover and renewal during a period of morphological changes. PMID- 1521065 TI - Developmental regulation of sialoadhesin (sheep erythrocyte receptor), a macrophage-cell interaction molecule expressed in lymphohemopoietic tissues. AB - Stromal macrophages in lymphohemopoietic tissues express novel macrophage restricted plasma membrane receptors involved in nonphagocytic interactions with other hemopoietic cells. One such receptor with lectinlike specificity for sialylated glycoconjugates on sheep erythrocytes and murine hemopoietic cells has been characterized immunochemically and termed sialoadhesin. We have examined sialoadhesin expression during mouse development to learn more about its regulation and function. Immunocytochemical, rosetting, and Western blot studies show that sialoadhesin is first detected on fetal liver macrophages on day 18 of development, 7 days after numerous F4/80+ macrophages are found within erythroblastic islands. In spleen and bone marrow, sialoadhesin appears between day 18 and birth, in parallel with myeloid development. Strongly labeled macrophages in the marginal zone of spleen, characteristic of adult lymphoid tissues, appeared gradually between 1-4 weeks after birth, as the white pulp became enlarged. Isolation of fetal liver macrophages at day 14 confirmed that sialoadhesin was not involved in the binding of erythroblasts, which is mediated by a distinct cation-dependent receptor (Morris et al., 1988, p. 649). Sialoadhesin could be expressed by isolated fetal liver macrophages after cultivation in adult mouse serum, a known source of inducer activity, but was not dependent on the presence of this inducer, unlike adult-derived macrophages. Fetal plasma contained inducing activity on day 13, but adult levels were not reached until 2 weeks postnatally. These studies show that sialoadhesin is differentially regulated compared with the erythroblast receptor and F4/80 antigen, that it is not required for fetal erythropoiesis, and that its induction on stromal macrophages is delayed until the onset of myeloid and lymphoid development. Sialoadhesin provides a marker to study maturation and functions of macrophages during ontogeny of the lymphohemopoietic system. PMID- 1521066 TI - [Drug passage through artificial membranes]. PMID- 1521067 TI - [The microbial status of implant surfaces]. PMID- 1521068 TI - [Autogenous and allogeneic cartilage transplants in head and neck surgery (excluding middle ear and trachea)]. PMID- 1521069 TI - [Transplantation of bones]. PMID- 1521070 TI - [Transplantation of nerves]. PMID- 1521071 TI - [Implants in middle ear surgery]. PMID- 1521072 TI - [Biocompatibility of cochlear implants]. PMID- 1521073 TI - [Tracheal transplantation in the animal]. PMID- 1521074 TI - [Transplantation of larynx and trachea in man]. PMID- 1521075 TI - [Tolerance of implantable alloplastic materials in the organism]. PMID- 1521076 TI - [Immunology of vital and preserved transplants]. PMID- 1521077 TI - [Social responsibility for organ donation. Legal aspects of modern transplantation surgery]. PMID- 1521078 TI - [Alloplastic implants in head and neck surgery]. PMID- 1521079 TI - [Metal implants in the area of head and neck surgery]. PMID- 1521080 TI - Dissociating graft-vs-host disease from the graft-vs-leukemia effect of allogeneic T cells: the potential role of IL-2. PMID- 1521081 TI - Unrelated donor marrow transplants for severe acquired aplastic anemia. AB - This report is divided into two parts. The first part is a retrospective analysis of 40 unrelated transplants [UD-BMT] for severe acquired aplastic anemia [SAA], performed at five transplant centers between 1981 and 1990. The second is an interim analysis of 15 UD-BMT for SAA compared with a matched cohort of 16 sibling transplants [ID-BMT] carried out since February 1989 using prospectively collected data provided by the IMUST Study Group. In the retrospective study the actuarial survival was 28% [+/- 15] with a median follow-up of 1485 [266-3890] days post BMT. Univariate analysis showed a considerable survival advantage for patients younger than 15 years at BMT [p = 0.03]. More recently patients entered in the IMUST Study showed an actuarial survival of 50% [+/- 27] for UD-BMT compared with 58% [+/- 31] for ID-BMT recipients. These data suggest that UD-BMT is a realistic option for paediatric patients with SAA. Although numbers are very small there is some indication from IMUST Study data that better patient selection and intensive BMT protocols may also improve the results of UD-BMT in young adult patients with SAA. PMID- 1521082 TI - Cord blood transplants: potential utility and potential limitations. AB - Cord blood has been utilized successfully for the hematopoietic reconstitution of children with lethal disorders of hematopoiesis, as an alternative to marrow derived stem cells. The majority of the transplants performed to date have utilized umbilical cord blood from HLA-identical siblings, however, much of the interest in this modality is due to its potential as a source of readily available unrelated stem cells. Cord blood offers intriguing theoretical advantages over the use of unrelated bone marrow, but additionally suffers from several limitations as well. This review is intended to highlight a number of these issues, rather than to serve as a detailed review of the clinical experience with cord blood transplantation to date. PMID- 1521083 TI - Late complications of allogeneic and autologous marrow transplantation. PMID- 1521084 TI - Harnessing graft versus leukemia: implications for IL-2 treatment. PMID- 1521085 TI - Cancer after bone marrow transplantation. IBMTR and EBMT/EULEP Study Group on Late Effects. AB - Cancer may be serious late effect of marrow transplantation. Radiation, chemotherapy, immunosuppression and the original disease for which transplantation was performed may predispose to the development of cancer. 116 of 9732 patients reported to the IBMTR (International Bone Marrow Transplant Registry) have developed a new malignancy. Late effects were evaluated by the EBMT-EULEP (European Bone Marrow Transplant-European Late Effect Project) Late Effect Study Group in 147 patients surviving 6 years and 79 patients surviving more than 10 years. New malignancies developed in 11 of these patients. Lymphomas and leukemia comprised 73 cases reported to the IBMTR and one case reported to the EBMT-EULEP study. Tumors of the skin, oropharynx, vulva vagina and cervix prevailed in 41 patients with solid tumors. The distribution of malignancies is similar to that observed in organ transplant patients not given radiation or chemotherapy and suggests immunosuppression as a major contributory factor. In dogs the incidence of malignancies was studied after either chemotherapy or total body radiation in various regimens and marrow transplantation. Both chemotherapy and radiation shortened tumor-free survival in comparison to untreated dogs. Higher doses, larger fractions and shorter treatment schedules enhanced earlier tumor development. Soft tissue sarcomas and thyroid carcinoma were most frequent in treated, mammary carcinoma in untreated dogs. In treated dogs deaths from cancer were observed starting at the age of 5 years as compared to untreated dogs at the age of 9 years. The data from animal experiments indicate that the incidence of solid tumors in marrow transplant patients may still rise in the coming decades. PMID- 1521086 TI - Autologous graft-versus-host disease: a new frontier in immunotherapy. PMID- 1521087 TI - Transplants in AML. AB - Three therapies are widely-used to treat acute myelogenous leukemia (AML): allogenic bone marrow transplants, autotransplants and chemotherapy. Which of these therapies is best is controversial. Analyzing and comparing results of these therapies is complex and controversial. Comparisons of published data are flawed by biased reporting and subject selection. Randomized trials are also reported but are limited by small numbers of subjects and the question of whether their conclusions apply to most persons with AML. Hypotheses being tested in randomized trials are often misunderstood or relevant to only a subset of persons with AML. Furthermore, in many trials a substantial proportion of subjects do not receive the intended treatment. Observational data bases are also used to compare results of different AML therapies. Although this is probably the most effective analytic approach, substantial differences in outcome-related variable between treatment groups make complex statistical adjustment necessary. Validity of these adjustments is controversial. Limitations of these diverse approaches to comparing results of different therapies of AML suggests that a precise answer to the question of how best to treat AML is unlikely to be forthcoming. This uncertainty is further confounded by the considerable subjectivity that influences how physicians choose between alternative therapies. The net result of these considerations is a consensus approach to treating AML is unlikely to develop, probably because results of diverse treatments are not very different. PMID- 1521088 TI - Transplants in ALL. PMID- 1521089 TI - Changing trends in marrow transplantation for aplastic anemia. PMID- 1521090 TI - T cell tolerance after bone marrow transplantation in mice. AB - This article provides a brief overview of T cell tolerance induction in the thymus, using parent----F1 bone marrow (BM) chimeras as a model. Although intrathymic tolerance is controlled largely by BM-derived cells, experiments with BM chimeras suggest that thymic epithelial cells can make a major contribution to tolerance induction, especially for high-affinity T cells. Whether extrathymic mechanisms contribute to tolerance induction remains controversial: evidence against this possibility is provided by the finding that transferring normal parental strain T cells to parent----F1 chimeras leads to immunogenicity rather than tolerogenicity. Breakdown of self tolerance is discussed in terms of the phenomenon of "auto-GVHD". PMID- 1521091 TI - Allogeneic bone marrow transplants for Fanconi anemia. A preliminary report from the International Bone Marrow Transplant Registry. PMID- 1521092 TI - Bone marrow transplantation in sickle cell diseases: a plea for a rational approach. PMID- 1521093 TI - Autologous bone marrow transplantation for patients with aggressive non-Hodgkin's lymphoma. PMID- 1521094 TI - Bone marrow transplantation in Hodgkin's disease. PMID- 1521095 TI - Is there a better way to deliver total body irradiation? AB - The available data suggest that the antileukemic, immunosuppressive and toxic effects of TBI are highly dose dependent and if TBI is given as single daily fractions at 5-10 cGy/minute, an optimal dose for the treatment of most leukemias is somewhere between 12 and 16 Gy. Giving radiation as a single dose rather than fractionating it increases both its immunosuppressive as well as its toxic effects. The relative anti-leukemic effects of single vs. fractionated irradiation are less clear, but available data support the view that fractionation does not substantially reduce the effects of TBI on myeloid tissue. Increasing the dose rate increases toxicities and, although data are not yet complete, likely increases both immunosuppressive and anti-tumor effects. The impact of total dose, dose fractionation and dose rate are highly interdependent and how best to manipulate these 3 factors to lead to an optimal combination is as yet unknown. Directing radiotherapy to sites of leukemia using monoclonal antibodies or other carriers such as growth factors is feasible and, although there are many aspects of this approach which have yet to be worked out, targeted radiotherapy may prove to be the best way to achieve the therapeutic goals of increased tumor ablation and immunosuppression without increased toxicities. PMID- 1521096 TI - Who should get a second marrow transplant? AB - Second transplants need to be considered in two clinical situations after marrow transplantation. Firstly, failure of sustained engraftment; secondly, recurrence of the underlying malignancy. In patients with failure of sustained engraftment a trial of recombinant human GM-CSF is indicated first with a chance of improving blood counts in a significant proportion of patients. If this is unsuccessful a second transplant utilizing a preparative regime aimed primarily at further minimizing host immune competence such as a combination of antithymocyte globulin (ATG) and cyclophosphamide or ATG alone followed by a T-replete marrow infusion should be employed. A second marrow transplant can also be utilized for recurrence of the underlying haematological malignancy after first transplant. However, several large multi-institutional studies have now shown a striking difference in the long-term leukemia-free survival rate between those relapsing early (for example, less than six months) after the first transplant compared to those relapsing later after the first transplant. Leukemia-free survival post second transplant for those relapsing within six months of first transplant is less than 10%, whereas for those relapsing greater than six months from first transplant it is approximately 30%. Transplant-related mortality, particularly from complications influenced by chemotherapy, such as interstitial pneumonitis and hepatic veno-occlusive disease, are more common after second than after first transplant.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1521097 TI - Allogeneic bone marrow transplantation for Niemann-Pick disease (type IA). PMID- 1521098 TI - State of the art review. Bone marrow transplantation treatment for storage diseases. Keystone. January 23, 1992. PMID- 1521099 TI - Wolman's disease: a review of treatment with bone marrow transplantation and considerations for the future. AB - Wolman's disease is a fatal disorder characterized by absence of acid lipase and accumulation of cholesterol esters. Inanition due to malabsorption and intractable diarrhea has been the most prominent cause of early demise within the first year. Further complications have included cirrhosis and pulmonary failure due to cholesterol ester storage in respective cells. Although sustained caloric balance can be maintained by total parenteral nutrition, this has not altered the eventual course of disease. The acid lipase deficiency in leucocytes in Wolman's disease can be corrected subsequent to bone marrow transplantation. This has proven to be the case in two patients so transplanted. In two other patients, engraftment was not obtained following bone marrow transplantation. The concept of treatment of Wolman's disease by providing normalization of the acid lipase activity by allogeneic bone marrow transplantation remains valid. However, improvement of bone marrow transplant procedure needs to be implemented since pre existing morbid pathology enhances toxicity and may prevent engraftment. Alternative modifications for accomplishing sustained engraftment without toxicity need to be examined. Other potential therapies need to be inspected in treatment of patients with Wolman's disease. The capability of reducing cellular cholesterol synthesis by use of lovastatin, an inhibitor of 3-hydroxy-3 methylglutaryl-CoA reductase, is now available. In the future, isolation and purification of acid lipase will allow for direct infusion of missing enzyme. The molecular biology now known concerning acid lipase gene holds promise for the future for recombinant manufacturing of acid lipase. And, gene therapy with its use of autologous bone marrow transplantation will be tried in future.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1521100 TI - Anger and irritability. PMID- 1521101 TI - Absence from school and mental health. AB - Severe school attendance problems, which once commanded a great deal of attention in child and adolescent psychiatry, have fallen from favour and are increasingly viewed as varieties of social impairment which may accompany disorders such as anxiety disturbances in the case of school refusal and conduct disturbances in the case of truancy. It is argued that this relegation of school attendance difficulties may have gone too far. As presenting complaints, albeit sometimes masked by apparent physical illness, they still have much to recommend them as indicators of a wide variety of present and future problems: educational, social, family, legal, medical, and, last but not least, psychiatric. Prevalence, features, causative factors, outcome, and management are discussed. Particular attention is paid to DSM and ICD classification. Gaps in present knowledge are indicated. PMID- 1521102 TI - Anna O. had a severe depressive illness. AB - The information available on the illness of Anna O. is reviewed together with follow-up data from the literature. It is concluded that the diagnosis of a severe depressive illness with depressive delusions is well justified. Hysterical symptoms which appeared can be understood as part of the depressive state modified by the expectations of the period and by the intervention of physicians. The illness was a very protracted one, with fluctuations or exacerbations lasting from 1880 to 1887, and was complicated by dependence upon morphine and chloral hydrate. However, by 1888, the patient appears to have made a considerable recovery, and she went on to lead an effective and fruitful life, demonstrating high intelligence and the resilience of the cyclothymic temperament. PMID- 1521103 TI - A comparison of academic and lay theories of schizophrenia. AB - This study investigated lay subjects' theories of schizophrenia. A questionnaire examining the five identified main academic theories of schizophrenia (medical, moral-behavioural, social, psychoanalytic, and conspiratorial) along various dimensions (aetiology, behaviour, treatment, function of the hospital, and the rights and duties of both patients and society) was constructed for use in the study. The results from 106 lay respondents showed that no single model was favoured exclusively but seemed to point to a synthesis of several academic theories. The lay subjects stressed the importance of patient environment in the aetiology of schizophrenia rather than a physiological malfunction, but tended to stress the personal rights of the schizophrenic. The differences between lay and the currently dominant psychiatric models are discussed in terms of the function these models serve for each group. PMID- 1521104 TI - Women whose mental illnesses recur after childbirth and partners' levels of expressed emotion during late pregnancy. AB - Expressed emotion (EE) in the partners of 25 pregnant women with a history of psychosis or severe depression and in 13 pregnant control subjects without any previous psychiatric disorder was assessed in the ninth month of pregnancy. At this time, no patient presented as a case according to RDC. Eleven subjects with a history of psychiatric disorder experienced a further episode of illness in the six months following delivery. Partners of women who became ill had made fewer critical and positive comments about their wives during the pregnancy than the partners of women who remained well. Poor self-rated social adjustment in the partners was also predictive of recurrence of illness after delivery. PMID- 1521105 TI - The influence of family expressed emotion on the course of schizophrenia in a sample of Spanish patients. A two-year follow-up study. AB - A sample of 60 Spanish schizophrenic patients was studied to ascertain the relationship between their relatives' expressed emotion (EE) and relapse at follow-up. The relatives' EE and patients' relapse were operationalised following Leff & Vaughn's criteria. At nine months a significant association was not found between the relatives' EE and relapse, but this association became significant on reclassifying the relatives' EE scores after decreasing to four points the cut off point for critical comments. At 24 months no association was found between EE and relapse. There was a tendency for patients who interrupted their medication or who did not work to relapse more frequently, particularly among the high-EE group. PMID- 1521106 TI - Alzheimer's disease, other dementias, depression and pseudodementia: prevalence, incidence and three-year outcome in Liverpool. AB - A group of 1070 community-living persons aged 65 and over was assessed using the GMS-AGECAT package and other interviews at years 0 and 3. Year 3 interviewers were 'blind' to the findings at year 0, and the prevalence of organic disorders and depression was very similar in both years. According to the results at year 3, minimum and maximum prevalence figures for dementia at year 0 were 2.4% and 3.8% for moderate to severe and 0.4% and 2.4% for mild or early cases, with a best estimate of 3.5% and 0.8%, or 4.3% overall, divided into: senile, Alzheimer's type 3.3%; vascular 0.7%; and alcohol-related 0.3%. The overall incidence of dementia, clinically confirmed by six-year follow-up, was 9.2/1000 per year (Alzheimer type 6.3, vascular 1.9, alcohol related 1.0). Three years later, 72.0% of those with depressive psychosis and 62.3% of those with depressive neurosis were either dead or had some kind of psychiatric illness. Nearly 60% of milder depressive cases (7.2% of the total sample) had either died or developed a chronic mental illness. The outcome of depressive pseudodementias is equivocal so far. Findings at year 3 provide validation of AGECAT computer diagnosis against outcome; organic and depression diagnoses are seen to have important implications for prognosis. PMID- 1521107 TI - Alexithymia in women with anorexia nervosa. A preliminary investigation. AB - The prevalence of alexithymia in 48 female anorexia nervosa patients was 77.1% compared with a prevalence of 6.7% in 30 normal female subjects, matched by age and education. Alexithymia correlated negatively with education in the anorexic patient group, but was unrelated to duration of illness, amount of weight loss, and levels of depression and of general psychoneurotic pathology. PMID- 1521108 TI - Frontal lobology--psychiatry's new pseudoscience. PMID- 1521109 TI - Neurosyphilis and schizophrenia. AB - Neurosyphilis continues to present in atypical forms, leading to erroneous diagnoses by physicians and psychiatrists. This patient, with a previous history of psychosis, presented in a catatonic state with rhabdomyolysis and renal failure. A subsequent breakdown was thought to be schizophrenic until unusual features led to a reassessment and discovery of neurosyphilis which was treated with penicillin and resulted in a remarkable clinical recovery. PMID- 1521110 TI - Neuroleptic malignant syndrome presenting as hyperosmolar non-ketotic diabetic coma. AB - A 50-year-old man presented with hyperosmolar non-ketotic diabetic coma associated with the neuroleptic malignant syndrome (NMS) after intramuscular treatment with haloperidol. It is suggested that NMS may occur as a complication of uncontrolled diabetes mellitus with dehydration. Conversely, NMS might precipitate diabetic coma in patients with previously well controlled blood glucose. PMID- 1521111 TI - Life-threatening allergic reaction to clozapine. AB - Clozapine, an 'atypical' antipsychotic drug, rarely induces allergic complications, which usually present as cutaneous reactions. We report the case of a 69-year-old woman, suffering from chronic schizophrenia, who developed an allergic asthmatic reaction following clozapine therapy. Intensive-care treatment was necessary. The reaction could be repeated by further exposure to the drug. Skin tests for hypersensitivity were negative. PMID- 1521112 TI - Successful treatment of episodic dyscontrol with carbamazepine. AB - Following a road-traffic accident, an 18-year-old man developed episodic dyscontrol which brought him into conflict with the law. Two years after the accident, treatment with carbamazepine was initiated and further aggressive outbursts subsided. The efficacy and mode of action of carbamazepine is discussed and the literature reviewed. PMID- 1521113 TI - Visual hallucinations as the presenting symptom of senile dementia. AB - A case of senile dementia that initially presented with complex visual hallucinations in the absence of clinical cognitive impairment or other psychopathology is described. Dementia must be added to the differential diagnosis of isolated visual hallucinations in the elderly. PMID- 1521114 TI - Self-neglect in adult life. AB - Two cases of self-neglect in adult patients with no psychiatric diagnosis are reported. The presentation included domestic squalor and hoarding of rubbish, with the patients living alone and having a history of schizoid and paranoid personality traits. Both refused all recommended help. A move to more protected accommodation was the only practical measure that led to a degree of improvement. PMID- 1521115 TI - Manufacture of multiple personality disorder. PMID- 1521116 TI - Sertraline in the prevention of depression. PMID- 1521117 TI - Setraline in the prevention of depression. PMID- 1521118 TI - Reports of the death of factor analysis are greatly exaggerated. PMID- 1521119 TI - Influenza and schizophrenia in Japan. PMID- 1521120 TI - Schizophrenia following prenatal exposure to influenza epidemics between 1939 and 1960. PMID- 1521121 TI - Declining incidence of hysteria. PMID- 1521122 TI - Anorexia nervosa and XY gonadal dysgenesis. PMID- 1521123 TI - Propofol and ECT. PMID- 1521124 TI - Hemisphere dysfunction in psychiatric disorders. PMID- 1521125 TI - Ventricular size in schizophrenia. PMID- 1521126 TI - Hemisphere dysfunction in psychiatric disorders. PMID- 1521127 TI - Hypertrichosis in mentally ill women. PMID- 1521128 TI - Women and scientific thought. PMID- 1521129 TI - Descriptions of psychiatric conditions in literature. PMID- 1521130 TI - Taking liberties'. PMID- 1521131 TI - Neuroleptic-induced dislocation of the jaw. PMID- 1521132 TI - Organic mood syndrome in two siblings with Wolfram syndrome. PMID- 1521133 TI - Psychosis, epileptiform abnormalities and clozapine. PMID- 1521134 TI - Catatonia and creatinine phosphokinase. PMID- 1521135 TI - Increases in extracellular dopamine levels and locomotor activity after direct infusion of phencyclidine into the nucleus accumbens. AB - Three studies were conducted to provide a further characterization of the neurochemical and behavioral effects of phencyclidine (PCP). The first experiment utilized in vivo microdialysis to measure extracellular levels of dopamine (DA), dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) in the nucleus accumbens. Administration of PCP (4.0 x 10(-4) M) in the dialysis perfusion medium produced large increases in extracellular DA, and biphasic changes in DOPAC. In the second experiment, chronic indwelling cannulae for drug infusion were implanted bilaterally into the nucleus accumbens. Local infusions of PCP (15.0, 30.0 or 60.0 micrograms per side) produced substantial increases in locomotor activity. Little or no headweaving, stereotypy or ataxia was observed after intra-accumbens injections of PCP. In the third experiment, systemic administration of 0.4 mg/kg haloperidol significantly reduced the locomotor activity induced by intra-accumbens injection of 15.0 micrograms PCP. These results indicate that PCP can increase extracellular levels of DA by direct actions in the DA terminal region, and that these effects are related to some of the behavioral stimulant properties of PCP. PMID- 1521136 TI - Cholinergic and GABAergic neurons occur in both the distal and proximal turtle retina. AB - Turtle retinas were processed immunocytochemically and histochemically to detect the presence of choline acetyltransferase (ChAT), acetylcholinesterase (AChE), and glutamate decarboxylase (GAD). We observed cholinergic and gamma-aminobutyric acid (GABA)ergic neurons in the proximal retina, as expected, and in the distal retina as well. ChAT immunoreactivity in the distal retina was observed within the axons and pedicles of numerous cone photoreceptors, suggesting that a population of turtle cone photoreceptors uses ACh as a neurotransmitter. Type L2 horizontal cells were immunoreactive for GAD, and their dendrites invaginated into cone pedicles. AChE histochemistry revealed processes within the outer plexiform layer which formed a loosely organized lattice. In the proximal retina, labeling for ChAT and GAD was similar to that reported by previous investigators. Processes from ChAT-labeled amacrine cells in the inner nuclear layer formed a stratum within the distal inner plexiform layer (IPL) (at 16-21% relative IPL depth), and processes from ChAT-labeled amacrines in the ganglion cell layer formed a proximal ChAT stratum (at 55-58% relative IPL depth). In addition, six AChE-labeled bands and five GAD-labeled bands were observed within the IPL of stained retinas. Therefore, we determined that the two broadest AChE-labeled bands and the two broadest GAD-labeled bands overlapped the two labeled ChAT strata. The evidence for cholinergic and GABAergic processes in both the inner plexiform layer and the outer plexiform layer, combined with electrophysiological evidence from other investigators, raises the possibility that distal retinal neurons may be involved in the encoding of directional information. PMID- 1521137 TI - Overlap between acetylcholinesterase-rich and choline acetyltransferase-positive (cholinergic) axons in human cerebral cortex. AB - The distribution of acetylcholinesterase-rich axons was compared to that of choline acetyltransferase-positive (cholinergic) axons in 28 major cytoarchitectonic divisions of the adult human cerebral cortex. Acetylcholinesterase-rich as well as choline acetyltransferase-positive cortical axons contained multiple varicosities. Each type of axon was more densely distributed in limbic-paralimbic regions of the brain. In all the cortical areas that were examined, the two markers displayed laminar and regional distribution patterns that were indistinguishable from each other. A method that allowed the concurrent visualization of both reaction products demonstrated that acetylcholinesterase and choline acetyltransferase were colocalized in the same axon. These observations show that there is probably a complete correspondence between choline acetyltransferase-positive and acetylcholinesterase-rich axons and that the acetylcholinesterase reaction can be used as a specific marker for cortical cholinergic axons in the adult human brain. PMID- 1521138 TI - Somatotopic maps within the zona incerta relay parallel GABAergic somatosensory pathways to the neocortex, superior colliculus, and brainstem. AB - Neurons located in the zona incerta (ZI) of the ventral thalamus project to several regions of the central nervous system, including the neocortex, superior colliculus, and brainstem. However, whether these projections are functionally segregated remains unknown. This issue was addressed here by combining neuroanatomical tracers with immunohistochemical staining for gamma-aminobutyric acid (GABA) and/or parvalbumin, coupled with neurophysiological mapping. GABAergic projection neurons were found in four distinct subregions of the ZI including: (1) the rostral pole of the ZI, from which neurons project to the supragranular layers of the neocortex (especially layer I); (2) the dorsal subregion of the ZI, where both ascending projections to the neocortex and descending projections to the pretectal area were observed; (3) the ventral subregion of the ZI, whose neurons project to the superior colliculus; and 3) the caudal pole of the ZI, from which descending projections to the lower brainstem and spinal cord were observed. Somatotopic representations of the contralateral cutaneous periphery were also identified in the dorsal and ventral subregions of ZI, both of which were found to receive dense direct afferent projections from the trigeminal complex, and dorsal column nuclei. These results suggest that the rat ZI is a major somatosensory relay in the ventral thalamus, carrying feed forward inhibitory signals to neocortical and subcortical targets, in parallel with the excitatory somatosensory pathways. PMID- 1521139 TI - NPY-like immunoreactivity in sensory nerve fibers in rat sciatic neuroma. AB - Neuropeptide Y (NPY)-like immunoreactivity was examined by fluorescence immunohistochemistry in rat sciatic neuromas, L5 dorsal root ganglias (DRGs) and L5 dorsal roots 1-3 weeks after chronic nerve injury. Anterograde tracing demonstrated that a large number of NPY-positive neuroma fibers were sensory. These fibers were mostly large diameter axons, in line with the finding that a majority of NPY-immunoreactive neurons in the DRG were medium- to large-sized neurons which showed immunoreactivity to the neurofilament antibody RT 97. In dorsal roots NPY immunoreactivity was strong after sciatic neuroma formation. Dorsal rhizotomy and ligation, on the other hand, did not induce NPY immunoreactivity at any of the sites examined. PMID- 1521140 TI - Inhibitory neuron produces heterosynaptic inhibition of the sensory-to-motor neuron synapse in Aplysia. AB - We have identified an inhibitory neuron (RPL4) in the right pleural ganglion of Aplysia, which produced hyperpolarization of the sensory and motor neurons involved in the tail withdrawal reflex. Activation of RPL4 significantly reduced the amplitude of excitatory postsynaptic potentials produced in tail motor neurons by action potentials triggered in sensory neurons. This example of heterosynaptic inhibition was due, at least in part, to an increase in membrane input conductance in the motor neuron. Since the synaptic strength of the sensory to-motor neuron connection has been associated with the strength of the tail withdrawal reflex, RPL4 may contribute to modulation of that reflex. PMID- 1521141 TI - Angiotensin II excites vasomotor neurons but not respiratory neurons in the rostral and caudal ventrolateral medulla. AB - We examined the vasomotor and respiratory effects of angiotensin II microinjection into the rabbit ventrolateral medulla (VLM). Angiotensin II in the rostral and caudal VLM increased and decreased arterial pressure, respectively, but had no effect on phrenic nerve activity. In contrast, L-glutamate injections in the same areas altered both arterial pressure and phrenic nerve activity. The results suggest that angiotensin II may activate specifically vasomotor neurons but not respiratory neurons in the VLM. PMID- 1521142 TI - Repeated stress enhances vasopressin synthesis in corticotropin releasing factor neurons in the paraventricular nucleus. AB - The effect of repeated stress on corticotropin-releasing factor (CRF) and vasopressin (AVP) synthesis in parvocellular neurons of the paraventricular nucleus (PVN) was studied by means of double label immunocytochemistry. Once daily immobilization of male rats for 16 days leads to a 75% increase in the number of CRF immunoreactive neurons, but a 5-fold elevation in the number of AVP containing CRF cell bodies. These results demonstrate that repeated stress activates AVP synthesis in CRF neurons. PMID- 1521143 TI - Transient c-fos expression and dendritic spine plasticity in hippocampal granule cells. AB - A transient expression of Fos protein occurs in nuclei of partially deafferented dentate granule cells within 1 h of transecting perforant path and fornix inputs. This was followed within 24 h by widening of spine necks, elaboration of the spine apparatus, and appearance of coated vesicles, multivesicular bodies, and ribosomes in remaining spines. This study supports the hypothesis that immediate early genes such as c-fos activate late response genes for generating building blocks of plasticity in partially deafferented neurons of adult rats. PMID- 1521144 TI - Fine structure and possible origins of nerve fibers with corticotropin-releasing factor-like immunoreactivity in the rat central amygdaloid nucleus. AB - The fine structure of nerve fibers with corticotropin-releasing factor (CRF)-like immunoreactivity in the central amygdaloid nucleus and CRF-containing afferents to the nucleus were investigated by pre-embedding immunoelectron microscopy and by the combination of fluoro-gold tracing and the indirect immunofluorescence method. Significant numbers of CRF nerve endings and dendrites formed synapses with non-immunoreactive dendrites and axon terminals, respectively. Axon terminals devoid of CRF frequently made synapses with the soma of immunoreactive and non-immunoreactive neurons; CRF nerve endings in contact with the soma were fewer in number. Occasionally, CRF was localized to both pre- and postsynaptic structures in the central amygdaloid nucleus. After fluoro-gold injection into the central amygdaloid nucleus and adjacent areas, double-labeled cells with the tracer and CRF were observed mainly in the lateral hypothalamic area and occasionally in the dorsal raphe nucleus, and they were less numerous than single labeled cells. These findings suggest that part of the CRF axon terminals identified in the electron micrographs arises from neurons in the lateral hypothalamic area and the dorsal raphe nucleus and the others from intra amygdaloid CRF neurons. The immunoreactive dendrites are likely to derive from neurons in the central amygdaloid nucleus, which are shown to send axons to the lower brainstem. Thus, this study demonstrates that CRF structures constitute a more complex neuronal network in the central amygdaloid nucleus than previously considered. PMID- 1521145 TI - Low magnesium-induced epileptiform discharges in guinea pig hippocampal slices: depression by the organic calcium antagonist verapamil. AB - The antiepileptic effects of the organic calcium channel blocker verapamil were tested in non-drug-induced epileptiform activities. Low Mg2+ epileptic field potentials (EFP) were elicited in hippocampal slices of guinea pigs. Verapamil reduced frequency of occurrence and amplitude of EFP until EFP failed. The EFP reappeared if verapamil was withdrawn from low Mg2+ solution. Elevating the KCl concentration from 4 to 8 mM resulted in shortening of the latency of EFP abolition by verapamil and prolongation of the depressive effects of verapamil following its withdrawal. The findings indicate that transmembraneous calcium fluxes play also an essential role in low Mg(2+)-induced epileptiform activities. PMID- 1521146 TI - Convulsive seizures in rats induced by N-methyl-D-aspartate injection into the massa intermedia. AB - The behavioral and electroencephalographic effects of N-methyl-D-aspartate (NMDA, 25 nmol/1 microliter) injection into the massa intermedia (MI) was examined in rats. The injection caused violent running/jumping and shrill vocalization without evidence of EEG seizure in the hippocampus (HP) and amygdala (AM). Animals with the injection site located in the reuniens nucleus subsequently developed generalized tonic and then clonic seizure, leading to fatal status epilepticus in some animals. Intermittent or continuous EEG discharge in the limbic system was found during clonic seizures. These findings suggest that the NMDA receptor in the reuniens nucleus in the MI participates in the generation and expression of convulsive seizure in rats. PMID- 1521147 TI - Ischemia-induced irreversible deficit of memory function in gerbils. AB - Ischemia for 5 min temporarily increased locomotor activity in gerbils after 1 and 3 days. Temporary increases were also noted within 7 and 5 days after 20-min ischemia and repeated ischemia (three 2-min ischemia at 1-h intervals), respectively. In a passive avoidance task, gerbils were trained 2 or 14 days before the occlusion and then tested 1 day after it. Shortened step-through latency was observed in the retention test 3 days after 5-min ischemia, but not after 15 days (reversible deficit). In contrast, following 20-min ischemia, the step-through latency was significantly lower after 3 days and also after 15 days (irreversible deficit). Working memory was also tested with gerbils trained for an 8-arm radial maze task. A significantly higher working error was observed 1 day after 5-min ischemia but not after 5 days (reversible deficit). However, ischemia for 20-min and repeated ischemia led to markedly increase working error 1 day after the occlusion, with significant increases even after 14 and 28 days (irreversible deficit). In addition, while 5-min ischemia occurred the neuronal death in the hippocampal CA1 subfield, 20-min ischemia produced it not only in the CA1 subfield but also in the CA2-4 subfield and dorsal striatum. These results indicated that 5-min ischemia led to a reversible memory deficit, while 20-min and repeated ischemia produced an irreversible deficit. PMID- 1521148 TI - Preferential uptake of rubidium from extracellular space by glial cells compared to neurons in leech ganglia. AB - Glial cells play a significant role in maintaining extracellular space (ECS) potassium (K) by temporarily buffering or accumulating excess ECS K and then returning that K to neurons. Yet, little is known about the relative affinity of neurons or glial cells for K when both cells are simultaneously exposed to the same ECS K, in situ. Also, the process by which glial cells return K to neurons remains unknown. Therefore, electron probe X-ray microanalysis was used to measure rubidium (Rb) uptake, as a K tracer, into leech packet neurons and glial cells, and to measure the distribution of cell water content, K, Na and Cl. When ECS Rb was increased from 4 mM to 20 mM, there was a clear preferential Rb uptake into glial cells compared to neurons. At 4 mM extracellular Rb there was only a small difference between uptake velocity of neurons and glial cells (maximum mean uptake velocity at 4 mM Rb was 1.09 for glia, and 0.41 mmol Rb/kg dry wt/s for neurons), whereas at 20 mM extracellular Rb, glial uptake velocity was dramatically greater than of neurons (max. mean Rb uptake velocity for glia was 4.3 compared to 1.47 mmol Rb/kg dry wt/s for neurons). Glial Rb uptake velocity was enhanced by low temperature (max. mean Rb uptake velocity at 20 mM ECS Rb at 6 degrees C was 6.04 for glia compared to 0.78 mmol Rb/kg dry wt/s for neurons) and by substitution of Cl with isethionate (max. mean Rb uptake velocity was 10.6 for glia compared to 1.33 mmol Rb/kg dry wt/s for neurons).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1521149 TI - Electroacupuncture modifies the expression of c-fos in the spinal cord induced by noxious stimulation. AB - The present study was designed to investigate the effect of 4 Hz vs. 100 Hz electroacupuncture (EA) on c-fos expression in the spinal cord induced by noxious stimulation (NS). A second objective was to evaluate the sensitivity of these two different frequencies of EA stimulation to the opiate antagonist, naloxone. Mechanical NS was applied to the right hindpaw following 30 min of either 4 Hz or 100 Hz EA treatment and the resulting c-fos expression in the spinal cord dorsal horn was compared to that obtained in rats exposed only to the noxious stimulation. The involvement of endogenous opioids in the EA response to 4 Hz or 100 Hz stimulation frequencies was evaluated by pretreating rats with naloxone (5 mg/kg, i.p.) 10 min prior to EA. Both 4 Hz and 100 Hz EA reduced the number of c fos-immunoreactive neurons in the spinal dorsal horn induced by noxious stimulation by 58% and 50%, respectively. The suppression of c-fos expression induced by 4 Hz EA was completely reversed by prior treatment with naloxone. On the other hand, the suppression of c-fos induced by 100 Hz EA was only partially blocked by this opiate antagonist. These data indicate that both high- and low frequency EA are capable of inhibiting the expression of c-fos in the dorsal horn induced by NS. Low-frequency EA appears to be mediated primarily by endogenous opioid systems, while non-opioid mechanisms may be involved in mediating the analgesic effect of high frequency EA. These results support the hypothesis that EA has a direct inhibitory effect on spinal cord dorsal horn neurons and extend the results of previous studies which indicate low frequency EA is mediated by opiate sensitive circuitry, while high frequency EA is predominantly mediated by non-opioid neurotransmitters. PMID- 1521150 TI - Basic fibroblast growth factor-like immunoreactivity in the trigeminal proprioceptive and motor systems. AB - Basic fibroblast growth factor (bFGF) isolated from the brain and pituitary, has been shown to induce cell divisions in a variety of cell types. It also acts as a potent stimulator of angiogenesis, and it is important in the survival of several types of cultured neurons. Despite considerable information on the functions of bFGF, there is incomplete knowledge about the ways in which it reaches remote tissues and its subcellular localization in the adult brain. Here we report our findings that a certain population of neurons with free ribosomes and rough endoplasmic reticulum immunoreactive for bFGF in the mesencephalic nucleus of the trigeminal nerve sends proprioceptive fibers to muscle spindles in the masseter muscle, and immunoreactive axons to the trigeminal motor nucleus to form synapses with the bFGF-containing motoneurons whose axons further constitute myoneural junctions in the periphery. Moreover, some bFGF neurons contain electron dense immunoreaction deposits in the euchromatin but not in the heterochromatin of the nucleus. These findings suggest that endogenous bFGF is transported within nerve processes and functions in mature neuronal circuits subserving the masseteric reflex arcs, and that bFGF is produced in free ribosomes and/or rough endoplasmic reticulum and is transported into the genetically active euchromatin as well. PMID- 1521151 TI - Comparison of the effects of chronic water deprivation and hypertonic saline ingestion on cerebral protein synthesis in rats. AB - The effects of 3 days water deprivation and 3 days with 2% (w/v) NaCl in drinking water on local rates of methionine incorporation into brain proteins were compared by means of a quantitative autoradiographic method with L [35S]methionine. The two conditions of chronic dehydration resulted in large increases in the rate of methionine incorporation in the supraoptic (SON), magnocellular paraventricular (mPVN) and arcuate nuclei of the hypothalamus, and in the subfornical organ (SFO). Significant increases of lower amplitude occurred as a result of both treatments in the anteroventral third ventricle area, parvocellular paraventricular nucleus and locus coeruleus. Water deprivation caused larger increases of protein synthesis than hypertonic saline ingestion in the SON, mPVN and SFO. These results indicate that following chronic dehydration, increases in protein synthesis occur mainly in forebrain areas involved in the regulation of water balance, whereas no major changes in protein synthesis occur in brainstem areas involved in the control of blood volume and pressure. PMID- 1521152 TI - Effects of intra-ischemic blood pressure on outcome from 2-vessel occlusion forebrain ischemia in the rat. AB - Halothane anesthetized Sprague-Dawley rats underwent 10 min of bilateral carotid artery occlusion with mean arterial pressure (MAP) held at 30, 50 or 60 mmHg. Sham rats did not undergo ischemia. A 7-day recovery interval was allowed. Intra ischemic electroencephalographic (EEG) changes, behavioral function (Days 5-7), and histologic injury (Day 7) were evaluated. Under similar conditions, cerebral blood flow was determined after 10 min ischemia by the [3H]nicotine indicator fractionation technique. EEG isoelectricity was observed in 11 of 11, 5 of 10, and 2 of 11 rats in the 30 mmHg, 50 mmHg, and 60 mmHg groups respectively. Neither passive avoidance cross-over latencies nor general motor scores were affected by intra-ischemic MAP and no differences from sham performance were observed. The per cent of CA1 neurons counted as dead (left and right hemispheres combined) was significantly affected by intra-ischemic MAP (72, 46 and 28% in the 30 mmHg, 50 mmHg, and 60 mmHg groups, respectively; P less than 0.001). A greater than 50% CA1 neuronal mortality rate was present only in those rats exhibiting EEG isoelectricity. However, the number of rats demonstrating greater than a 25% interhemispheric difference in CA1 neuronal loss was greatest in the 50 mmHg group (P less than 0.02). Hippocampal blood flow decreased in association with severity of hypotension (8 +/- 1, 35 +/- 8, and 48 +/- 2 ml/100 g/min (mean +/- S.E.M.) for 30, 50, and 60 mmHg, respectively; P less than 0.01). Again, however, the greatest variability in blood flow was observed at MAP = 50 mmHg.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1521153 TI - Rapid changes in ascorbate and dopamine release in rat nucleus accumbens after intracerebroventricular administration of NMDA. AB - In vivo voltammetry at electrochemically pretreated carbon fibre electrodes was used to investigate the effect of intracerebroventricular (i.c.v.) administration of N-methyl-D-aspartic acid (NMDA) on neuronal activity in rat nucleus accumbens. Infusion of a low dose of NMDA (1 nmol) was followed a few minutes later by rapid changes in both Peak 1 and Peak 2 heights indicating large but short-lived increases in the extracellular concentrations of ascorbate and catecholamines, respectively. These responses did not seem to be dependent on the dose infused since infusion of NMDA for a longer time period neither changed the amplitude nor the time-course of these effects. The increase in Peak 2 height was resistant to pargyline pretreatment indicating that this response mainly reflected the release of dopamine. The administration of NMDA was followed by behavioural activation in the animals but not convulsions. Co-administration of the competitive NMDA receptor antagonist, CPP (1 nmol), completely blocked these effects while the acetylcholine receptor antagonist, atropine (1.5 nmol), and the GABA receptor antagonist, picrotoxin (1 nmol), failed in this respect. The phenomenon spreading depression is discussed as a possible explanation of these results. PMID- 1521154 TI - In vivo protection of striatum from MPP+ neurotoxicity by N-methyl-D-aspartate antagonists. AB - The present study was designed to assess by microdialysis whether N-methyl-D aspartate (NMDA) non-competitive receptor antagonist, MK-801, is able to protect dopaminergic neurons against 1-methyl-4-phenylpyridinium ion (MPP+) neurotoxicity. An intraperitoneal injection of MK-801, 10 mumol/kg, half an hour before striatal MPP+, 10 mM, perfusion did not protect against its neurotoxicity. Afterwards, rats received an intraperitoneal injection of MK-801 every 4 h, during 24 h. Under these conditions, one day after MPP+ perfusion, DA basal extracellular levels were close to the detection limit of our HPLC equipment in both control and MK-801 treated rats. 3,4-Dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) basal output were lower in the former than in the latter rats. A second MPP+ perfusion statistically increased extracellular levels of DA and decreased DOPAC and HVA output in both groups of rats. However, the increase in extracellular DA overflow was higher in MK-801 treated rats than in the control group, indicating a higher number of surviving dopaminergic terminals. These results suggest that MK-801 is not able to protect against the primary direct neurotoxic action of MPP+, but a second MPP+ neurotoxic action mediated by excitatory amino acids could be partially prevented by MK-801. PMID- 1521155 TI - Limited and selective adduction of carboxyl-terminal lysines in the high molecular weight neurofilament proteins by 2,5-hexanedione in vitro. AB - 2,5-Hexanedione (2,5-HD) induces a toxic neuropathy characterized by massive, focal axonal neurofilament (NF) accumulation. Covalent interaction of 2,5-HD with NF protein amines, resulting in pyrrole adduct formation, has been proposed as a critical step in its mechanism. The present study was undertaken to evaluate the hypothesis of selective 2,5-HD/lysine modification, by quantitating in vitro adduction in the NF proteins and in specific polypeptide domains of each protein. Native rat spinal cord NFs were exposed to 0-212.5 mM [14C]2,5-HD for 2-16 h (37 degrees C under argon), followed by removal of non-covalently bound radioactivity. Incorporation of radioactivity and pyrrole formation in NFs increased linearly with 2,5-HD concentration and biphasically with time. SDS-PAGE and fluorography demonstrated prominent labeling of the three NF subunit proteins (H, M, and L), in addition to high-MW, crosslinked material derived from NF-H and -M. Mild chymotryptic cleavage was employed to isolate the carboxyl-terminal 'tail' domains of NF-H and -M, and the pooled amino-terminal NF 'rod' regions, all of which were radiolabeled. Specific activity (mol adduct/mol protein) of adducted NF proteins and polypeptide domains was determined by scintillation counting of electroeluted proteins. Stable binding in the NF-H and -M proteins was 4- to 6-fold higher than in the NF-L protein at all 2,5-HD concentrations, with specific activities of approximately 6.9, 4.7, and 1.3 mol/mol protein, respectively, at 212.5 mM. Approximately 70-80% of NF-H and -M binding was localized to the tail domains. In contrast, NF-L and pooled rod domain adduction did not substantially exceed 1 mol/mol protein. These findings provide the first direct evidence for limited and selective pyrrole adduction in the NF proteins following 2,5-HD exposure. PMID- 1521156 TI - Effects of dihydroergotoxine on central cholinergic neuronal systems and discrimination learning test in aged rats. AB - We evaluated changes in the cholinergic neuronal system and learning ability with aging. Choline acetyltransferase (ChAT) activity, a presynaptic index of the cholinergic system, was decreased in the cerebral cortex, hippocampus, striatum, and hypothalamus in the brain of aged rats compared with young adults. Muscarinic cholinergic binding sites (receptors, MCR), a postsynaptic index of the cholinergic system, were markedly decreased in all areas of the brain. However, intraperitoneal injection of 1 mg/kg of dihydroergotoxine (DHET) for 14 days normalized both ChAT and MCR in the cerebral cortex and hippocampus. In the striatum, ChAT was normalized, but MCR did not recover. Aged rats showed marked learning impairment in a 30-day operant type brightness discrimination learning test. Daily DHET administration restored the discrimination ability in the aged rats to nearly the young adult level. DHET had no effects on central cholinergic indices or learning test results in young adult rats. These findings suggest that learning is impaired in aged rats due to impairment in the central cholinergic neuronal system, and that DHET normalizes the decreased function in this system, restoring the learning ability. PMID- 1521157 TI - In vivo effects of beta-amyloid implants in rodents: lack of potentiation of damage associated with transient global forebrain ischemia. AB - Recent studies have shown that the principal component of the senile plaque in Alzheimer's disease (AD), beta-amyloid protein (beta AP) can exert direct and indirect neurotoxicity in vitro. Because of the studies that demonstrated potentiation of excitatory amino acid toxicity by beta AP, we decided to test whether beta AP was able to potentiate damage in an in vivo model where excitotoxic damage is thought to be important. The present study evaluated the in vivo effects of beta AP implants in the brain of rats before and after being subjected to 10 min of transient global forebrain ischemia by 4-vessel occlusion (4-VO). Implants of either synthetic beta AP or prolactin (PRL), which was used as a control protein, were made into the striatum and the hippocampus of either the left (beta AP) or the right (PRL) cerebral hemisphere. The implants were made in a lipophilic, non-toxic vehicle so as to try and achieve sustained beta AP exposure. One group of animals was evaluated for direct in vivo effects within 1 week following implantation; the other group was subjected to 4-VO 3-4 days post implantation for evaluation of potential indirect effects. This latter group was compared to the histopathology of animals subjected to 4-VO without prior implantation. In the group of animals evaluated for direct effects, no evidence of neurotoxicity was observed. Bielschowsky silver staining and immunostaining for ubiquitin were unremarkable in all lesions. beta AP was detected by immunocytochemistry in the parenchymal tissue that received beta AP implants. Marked glial activation was observed to be associated with experimental and control implants. Under the experimental conditions employed in this study, significant protection from ischemia rather than potentiation of damage was observed. These results suggest that beta AP may not be neurotoxic in rodents in vivo and that the lesions and/or trauma produced by the implantation procedure 3 4 days prior to 4-VO may have induced factors that were protective against ischemia-induced damage. PMID- 1521158 TI - In vivo intracellular correlates of hippocampal formation theta-on and theta-off cells. AB - Using urethane-anesthetized rat, intracellular recordings were made in hippocampal formation cells classified according to previously established criteria as either theta-on or theta-off, in order to further define the electrophysiological characteristics of these cells. Four cells classified as phasic theta-off cells had short duration spikes (less than 1 ms), high input resistances (54-61 M omega) and large fast afterhyperpolarizations (6-10 mV), thus sharing some of the properties of identified hippocampal interneurons. Phasic theta-off cells also exhibited rhythmic membrane potential oscillations (MPOs) ranging from 4 to 10 mV in amplitude during the simultaneous occurrence of extracellular theta field activity, but not during the occurrence of large amplitude irregular field activity (LIA). The MPOs of phasic theta-off cells were the same frequency as and were highly coherent with the extracellular theta field activity. In all four phasic theta-off cells the positive peak of the MPO was in phase with the positive peak of the local theta field activity. At the onset of extracellular theta field activity above 4-5 Hz, the membrane potentials of phasic theta-off cells showed a 5-10-mV hyperpolarizing shift, accompanied by MPOs without spike discharges. As theta frequency slowed down there was a return to baseline membrane potential levels and spike discharges occurred near the positive peak of the MPOs. The seven cells classified as phasic theta-on had longer duration spikes (greater than 1 ms), lower input resistances (22-36 M omega) and small (approx. 1.0 mV) fast afterhyperpolarizations, thus sharing some of the properties of hippocampal projection cells.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1521159 TI - Adrenalectomy or metyrapone-pretreatment abolishes cerebral metabolic responses to the serotonin agonist 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI) in the hippocampus. AB - 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI), a serotonin type 2 (5-HT2) agonist, elevates plasma corticosterone levels and reduces the cerebral metabolic rate for glucose (rCMRglc) in the hippocampus, a structure which possesses few 5 HT2 receptors but a large number of steroid receptors. To explore the hypothetical interaction between 5-HT and steroid mechanisms in the hippocampus, we measured rCMRglc in intact, adrenalectomized and metyrapone-pretreated rats after saline or DOI administration. Metyrapone pretreatment alone had no significant effect on rCMRglc, but adrenalectomy produced widespread rCMRglc increases in the cortex, hippocampus and monoaminergic brainstem nuclei. In intact rats, DOI 10 mg/kg reduced rCMRglc in limbic areas and increased it in the interanteromedial and paracentral thalamic nuclei. Metyrapone pretreatment and adrenalectomy abolished rCMRglc responses to DOI in hippocampal areas and enhanced those in thalamic nuclei. These results indicate that brain responses to DOI are dependent upon the functional state of the hypothalamus-pituitary-adrenal cortex axis. PMID- 1521160 TI - Effects of anticonvulsant drugs on axonal conduction in mammalian corpus callosum. AB - The frequency-dependent effect of various anticonvulsant drugs on the conduction in central axons was studied in the corpus callosum of rat and guinea pig brain slices from the parietal region. Extracellularly recorded compound action potentials (CAPs) were evoked by either single stimulus or high frequency stimulation (40-80 Hz). The CAP in rats consisted of an early component (fast axons, 1.2-1.8 m/s) and a late component (slow axons, 0.5-0.7 m/s), while in the guinea pig only the slow phase was observed. Diphenylhydantoin increased the latency of a single response by 10%, and had no effect on the CAP amplitude. In contrast, both phenobarbital and pentobarbital reduced the amplitude of singly evoked CAPs. Stimulation at high frequency alone decreased the CAP amplitude by 10-20%. Identical stimulation in the presence of the drugs further suppressed the CAP amplitude by an additional 31%, with varying degree of drug efficacy. The depressant effect was significant for the slow axons but the fast axons were virtually unaffected by any of the drugs. The results are consistent with the hypothesis that the antiepileptic drugs DPH, Phe and Pnt may block axonal conduction from an epileptic focus into neighbouring areas of the brain. PMID- 1521161 TI - Age-dependent changes in cat masseter nerve: an electrophysiological and morphological study. AB - The present study was undertaken to determine the manner in which aging affects the function and structure of the masseter nerve in old cats. Electrophysiological data demonstrated a significant decrease in the conduction velocity of the action potential in old cats compared with that observed in adult cats. Light microscopic analyses revealed an age-dependent decrease in axon diameter. Electron microscopic observations of the masseter nerve in the aged cats revealed a disruption of the myelin sheaths and a pronounced increase in collagen fibers in the endoneurium and perineurium. These morphological changes are discussed and then related to the decrease in conduction velocity which was observed in the electrophysiological portion of this study. PMID- 1521162 TI - The role of angiotensin, AT1 and AT2 receptors in the pressor, drinking and vasopressin responses to central angiotensin. AB - Angiotensin II (Ang II) given centrally produces an increase in blood pressure and motivation to drink. The physiological mechanisms that mediate the pressor response include release of vasopressin (AVP) and activation of the sympathetic nervous system. Using 2 new Ang II receptor antagonists, we were able to investigate the role of AT1 or AT2 receptors in mediating these effects. Adult male Sprague-Dawley rats were cannulated in the lateral ventricle and 5 days later catheterized in the carotid artery for blood pressure measurements. All experiments were carried out in conscious rats. Three treatments were given intraventricularly (i.v.t.), in 2 microliters artificial cerebrospinal fluid (ACSF) at 30 min intervals: (1) 50 ng Ang II, (2) 0.7 micrograms AT1 antagonist Losartan or 7.0 micrograms AT2 antagonist PD123177, followed by 50 ng Ang II, and (3) 50 ng Ang II, to test for recovery. Blood pressure and drinking measurements were recorded. Also, blood samples for assay of AVP were drawn at 1 or 3 min post injection in 2 separate groups of rats. We found that both Losartan and PD123177 significantly reduced release of AVP to Ang II 1 min post-injection. Losartan significantly blocked the pressor response (P less than 0.001), while PD123177 had no significant effect. Drinking was also antagonized by Losartan (P less than 0.05) and reduced (n.s.) by PD123177. The results suggest that the pressor response to Ang II (i.v.t.) is predominantly AT1 mediated, while the drinking and AVP responses may be mediated by both receptor subtypes. PMID- 1521163 TI - Absence of early destructive changes of cytoskeletal proteins after transient ischemia in the rat. AB - We examined the changes in immunoreactivity of microtubuli-associated protein (MAP) 2 in dendrites by immunohistochemical analysis following 20 min of cerebral ischemia in the rat. A decrease of immunoreactivity of MAP 2 in dendrites in the CA1 subfield of the hippocampus was observed on days 3 and 7 but not on day 1 after ischemia. Early destructive changes of this protein were not observed, a finding which was confirmed by polyacrylamide gel electrophoresis analysis. We elucidated one factor which indicated that destruction of the dendrites of CA1 pyramidal neurons would not take place any earlier than the destruction of the neurons themselves after ischemia in rats. PMID- 1521164 TI - Molecular cloning of two partial serotonin 5-HT1D receptor sequences in mouse and one in guinea pig. AB - The G protein coupled serotonin (5-HT) receptors, with seven membrane spanning domains, form a multigene family of which several members have been cloned and sequenced. The presence of 5-HT1D binding sites to our knowledge has not yet been reported in mouse. Here we describe the cloning and sequencing by the polymerase chain reaction (PCR) method of two 5-HT1D receptor sequences of the third cytoplasmic loop in mouse, strongly suggesting the existence of two 5-HT1D receptor genes, located on chromosome 4. A homologous sequence to one of them was cloned in guinea pig. PMID- 1521165 TI - [Triiodothyronine is needed for the acclimatization of brown trout (Salmo trutta) or rainbow trout (Oncorhynchus mykiss) to seawater]. AB - Brown and rainbow trout, held in freshwater at 13 +/- 1 degrees, were injected, every 3 days, with iopanoic acid (IOP: 5 mg/100 g body wt), an inhibitor of deiodination of thyroxine (T4) to triiodothyronine (T3). One group of IOP-treated rainbow trout was immersed in T3 (20 micrograms/l water). In IOP trout, plasma T3 fell to very low levels by day 7, while changes in T4 levels were less marked. In IOP + T3 trout plasma T3 increased fivefold, plasma T4 being unchanged. No mortality occurred and plasma osmolarity (OP) was not altered by any treatment. After direct transfer to seawater (30/1000), IOP trout were unable to acclimate to salinity: all died within 2 or 3 days, while the survival at day 3 was 100% in control brown trout and 45 and 74% in control and IOP + T3 rainbow trout respectively. OP increased more in IOP and less in IOP + T3 than in controls. There was a significant inverse correlation between T3, but not T4, plasma level, at the time of transfer and the OP 1 day later. In conclusion, although T3 does not play a significant role in osmoregulation in freshwater, T3 and therefore the deiodination of T4 into T3, were required for the development of hypo osmoregulatory capacity involved in acclimation of trout to seawater. PMID- 1521166 TI - [Demonstration of glutamate in primary sensory trigeminal neurons innervating dental pulp in rats]. AB - Primary sensory trigeminal neurons supplying the dental pulp of incisors in rats were labelled by retrograde axonal transport. Using an auto-metallographic intensification procedure, 48 hrs. after injection of wheat-germ colloidal gold in the pulp, gold particles were detected in the cytoplasm of the neurons as black granulations. Glutamate was found in 45-60% of the neurons by submitting ganglion slices to an anti-glutamate immuno-serum revealed by immunocytochemistry. Among the neurons supplying the dental pulp of incisors by their peripheral process, 70% are Glu+, 30% Glu-. These observations suggest that the population of neurons supplying the dental pulp is not functionally homogeneous and that Glu- neurons use a different neurotransmitter. The coexistence of Glu+ and Glu- neurons could also indicate that glutamate expression is modulated during the life of these neurons. PMID- 1521167 TI - [Specific induction by phorbol ester of the gene transcription and of the activity of ornithine decarboxylase in two control and transformed epithelial cell lines. Modulator effect of anti-inflammatory agents]. AB - The mechanism of ornithine decarboxylase (ODC) induction by phorbol ester (TPA) has been studied in two permanent epithelial cell lines, a control (Ctr) and a Benzo (a) pyrene transformed line (BaP-tr); the degree of ODC gene expression (ODC-mRNA) was evaluated in comparison to the ODC activity. A small dose of TPA (4 x 10(-8) M) highly induced ODC activity in these cells. The induction levels differed however, corresponding respectively to 4:1 (induced: basal ODC) in Ctr cells and to 2:1 in BaP-tr cells. This difference reflected the variation of ODC gene expression; the ODC-mRNA induction was 6:1 in Ctr cells and 3:1 in BaP-tr cells. Repetitive TPA treatment decreased the ODC induction in these cells, as compared to that resulting from a single TPA treatment. Studies of ODC modulation were performed in presence of anti-inflammatory agents. In the two cell lines, Indomethacin (anti-cyclooxygenase) did not change the level of ODC induction by TPA. Nordihydroguaiaretic acid (NDGA, anti-lipoxygenase) inhibited this induced ODC. These results differed from that obtained in vivo in mouse skin. Dexamethasone (DXME, anti-phospholipase A2) showed different action according to treatment time. Used together with TPA (t0), DXME inhibited ODC induction by the carcinogen; with three hours delay after TPA (t3), DXME treatment stimulated ODC in the cells. This divergent action may be reproduced by Actinomycin D, while Cycloheximide only exhibited constant inhibition. Studies now in progress suggested that the inhibition of TPA induced ODC by DXME may reflect ODC gene repression, as for the stimulating effect it could be related to ODC post transcriptional modulation, owing to the decrease of proteolytic action. PMID- 1521168 TI - [Analysis of frequency of DR3 allele in rapidly evolutive forms of Crohn disease in adults; comparison with the occurrence of this allele in slowly evolutive forms and in the normal population]. AB - This communication reports 1. the frequency of the DR3 allele among 86 patients exhibiting various evolutive courses of Crohn's disease (CD), diagnosed in the same hospital in Alsace, France, hospitalized at least once between 1964 and 1986 and followed for at least 1 year, 2. the frequency of the DR3 allele among a control population in the same area: 126 volunteers donors of bone marrow. The definition of the evolutive course was similar to the one published by Binder et al.: slow course (including: intermittent: "occurrence of symptom-free period(s) of at least one month's duration excluding period where the patient was in steroid treatment"; and inactive: "completely free of bowel symptoms during the year") as opposed to continuous evolution: "without symptom-free periods". The DR3 allele determination was established by classical serologic analysis. 26 patients were found with the DR3 allele; 14 belonged to the slow course group, 12 to the continuous evolution group; 60 patients did not exhibit the DR3 allele: 50 in the slow course group, 10 in the continuous evolution group. chi 2 = 8.28; p = 0.004. Therefore the frequency of the DR3 allele was very significantly higher in the group with the continuous course (55%) than in the slow course group (22%). Similarly the frequency of the DR3 allele in the group with the continuous course (12/22: 55%) was significantly higher than in the group of control subjects (34/126: 28%) chi 2 = 6.64; p = 0.01.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1521169 TI - [Inhibition of the tumoral growth induced by the injection of histo-incompatible cells producing interleukin-2]. AB - In murine models, we show that the growth of a transplanted tumor can be controlled when allogeneic or xenogeneic cells expressing high levels of interleukin-2 are co-injected with the syngeneic tumor cells. Thus, genetically modified allogeneic or xenogeneic cells could have some therapeutic potential as vectors for transient cytokine gene expression. PMID- 1521170 TI - [Influence of the distribution of the dose on carcinogenic effects of ionizing radiations of low lineal energy transfer on the thyroid tissue]. AB - The frequency of thyroid nodules has been studied among 396 children irradiated for a hemangioma, from 1946 to 1973. 226Ra, 192Ir, 90Y, 32P, 90Sr, as well as X rays had been used for treatments. The doses of radiation received by the thyroid of each child have been estimated retrospectively. The irradiations have been classified in two categories based on their duration: less than 30 min., and more than 30 min. The doses received with each of these two types of irradiation were summed for each patient. The risk of thyroid nodule increased as a function of the dose to thyroid only for the dose delivered with the short duration. This study emphases the importance of the role of the dose rate in the risk of radio induced tumour. PMID- 1521171 TI - [Demonstration of dissociation between frontal and temporal lesions in man on two versions of delayed non-matching recognition tests used in monkeys]. AB - 11 patients with frontal lobe lesions (F group), 9 patients with temporal lobe lesions (T group) and 18 normal control subjects (C group) were tested on two versions of the delayed non matching-to-sample task using either different pairs (DNMTS) or the same pairs of objects (RECURRENT) on successive test trials. The results revealed that the DNMTS task was sensitive to memory impairment but did not differentiate the two experimental groups. In contrast, the recurrent version of the task showed a dissociation between the two pathologies. Thus, whereas patients of group T exhibited an accelerated rate of forgetting as a function of the retention interval, patients of group F were impaired whatever the retention interval. PMID- 1521172 TI - Gram-scale enzymatic synthesis of a peptide bond. AB - The synthesis reaction of the peptide, N-Cbz-L-tryptophanyl-glycineamide, catalyzed by alpha-chymotrypsin was performed in a 20% water/80%, 1,4-butanediol mixture. The synthesis yield reached 90.9% at the end of the reaction and 72.3% after purification. The effects on the yield of both pH and the ratio between total initial concentrations of glycineamide and N-Cbz-L-tryptophan are examined. The high yield, specificity, simplicity and reproducibility of this method make it complementary of the chemical methods. PMID- 1521173 TI - [Expression, isolation and purification of antibody fragments fused to maltose binding protein in Escherichia coli]. AB - We have fused the variable domains of a mouse antibody to the C-terminal end of the maltose-binding protein (malE), at the genetic level. The hybrid proteins were expressed in E. coli under control of the malEp promoter, and exported to the periplasm, at low temperature. They were purified by affinity chromatography on cross-linked amylose. When the two variable domains were fused together through a peptide link, the hybrid displayed similar affinity and specificity to the antigen as the native antibody. PMID- 1521174 TI - [IgG autoantibodies against cellular p72 antigen crossing with (MLV) p15-gag antigen: presence in early HIV 1 infection, in HBV infection and in primary Gougerot-Sjogren]. AB - IgG antibodies of autoimmune SLE (Systemic Lupus Erythematosus) serum S detected a HeLa hnRNP 72 kDa protein, cross-reacting with the retroviral (MLV) p15-gag polypeptide. Since serum S disclosed a ubiquitous 72 kDa antigen in HeLa cell fractions, was prepared the so-called cytoplasmic "X fraction", enriched for the 72 kDa protein, defined here as p72. This autoantigen was detected by antibodies of HIV 1+ patients, recently of seroconverted (RSC) asymptomatic subjects, of HBV+ sera, and of primary Gougerot-Sjogren (prGS) sera. The presence of these autoantibodies in different autoimmune and infectious pathologies raises the question of the involvement of p72 in the immune processes and in the early HIV1 infection. PMID- 1521175 TI - [Excretion of urea and ammonia and its effect on the acid-base balance of water in the habitat of the anuran amphibian Xenopus laevis. Action of metabolic alkalosis]. AB - We studied in Xenopus laevis the effect of changing the salinity and the acid base status of the ambient water on the total nitrogen catabolism and the nature of the nitrogen end products, urea and ammonia. Increase of the ambient osmolarity by addition of NaCl led to a rise in protein catabolism and to a predominant ureotelism which can approach 95% of the excreted nitrogen. The osmolarity can reach 500 mosmol. L-1 without obvious harmful effects. NaCl can then be replaced by NaHCO3 without injury to the animal as long as water alkalosis is avoided by an appropriate increase of the ambient CO2 tension, PCO2. However, if PCO2 is kept low, the resulting water metabolic alkalosis causes death within a few hours. PMID- 1521176 TI - [Behavioral asymmetry in BALB/cCF mice with corpus callosum abnormalities]. AB - The possible homology between anomalies of the corpus callosum in mice and in humans remains questionable. The small number of existing behavioural studies in mice have not shown effects, at the behavioural level, of the absence or reduction in size of the corpus callosum. We therefore examined the development, during the first 3 weeks of postnatal life, of a number of simple reflex and integrative responses in the members of a sample of 101 BALB/cCF mice; at autopsy carried out at 50 days of age, 29 mice showed anomalies of the corpus callosum (total absence or an area less than 0.75 mm2). Asymmetry of the development of these responses was measured either as the proportion of animals showing asymmetrical appearance of responses on the left and right sides, and as the delay between appearances on the left and right sides in "asymmetrical" mice. Both measures decreased over the first 15 postnatal days, at the same rate in normal and abnormal mice; in each case the decrease is better described by a second-order, quadratic, function than by a simple linear function. We therefore conclude that the integrity of the corpus callosum is not necessary for the normal maturation of sensorimotor behaviour in mice, and suggest that this conclusion may possibly be explained by the relatively recent appearance of mice in the mammalian radiation. PMID- 1521177 TI - Sympathoadrenal system in neuroendocrine control of glucose: mechanisms involved in the liver, pancreas, and adrenal gland under hemorrhagic and hypoglycemic stress. AB - Glucose homeostasis is maintained by complex neuroendocrine control mechanisms, involving three peripheral organs: the liver, pancreas, and adrenal gland, all of which are under control of the autonomic nervous system. During the past decade, abundant results from various studies on neuroendocrine control of glucose have been accumulated. The principal objective of this review is to provide overviews of basic adrenergic mechanisms closely related to glucose control in the three peripheral organs, and then to discuss the integrated glucoregulatory mechanisms in hemorrhage-induced hypotension and insulin-induced hypoglycemia with special reference to sympathoadrenal control mechanisms. The liver is richly innervated by sympathetic and parasympathetic nerves. The functional implication in glucoregulation of sympathetic nerves has been well-documented, while that of parasympathetic nerves remains less understood. More recently, hepatic glucoreceptors have been postulated to be coupled with capsaicin-sensitive afferent nerves, conveying sensory signals of blood glucose concentration to the central nervous system. The pancreas is also richly supplied by the autonomic nervous system. Besides the well documented adrenergic and cholinergic mechanisms, the potential implication of peptidergic neurotransmission by neuropeptide Y and neuromodulation by galanin has recently been postulated in the endocrine secretory function. Presynaptic interactions of these putative peptidergic neurotransmitters with the classic transmitters, noradrenaline and acetylcholine, in the pancreas remain to be clarified. It may be of particular interest that it was vagus nerve stimulation that caused a dominant release of neuropeptide Y over that caused by sympathetic nerve stimulation in the pig pancreas. The adrenal medulla receives its main nerve supply from the greater and lesser splanchnic nerves. Adrenal medullary catecholamine secretion appears to be regulated by three distinct local mechanisms: adrenoceptor-mediated, dihydropyridine-sensitive Ca2+ channel-mediated, and capsaicin-sensitive sensory nerve-mediated mechanisms. In response to hemorrhagic hypotension and insulin induced hypoglycemia, the sympathoadrenal system is activated resulting in increases of adrenal catecholamine and pancreatic glucagon secretions, both of which are significantly implicated in glucoregulatory mechanisms. An increase in sympathetic nerve activity occurs in the liver during hemorrhagic hypotension and is also likely to occur in the pancreas in response to insulin-induced hypoglycemia. The functional implication of hepatic and central glucoreceptors has been suggested in the increased secretion of glucose counterregulatory hormones, particularly catecholamines and glucagon. PMID- 1521178 TI - Disparate effects of fenfluramine on thermogenesis in brown adipose tissue in the rat. AB - It has been suggested that fenfluramine, a clinically used appetite suppressant, can also promote weight loss by augmenting energy expenditure, as indicated by increased whole-body O2 consumption (VO2) and mitochondrial GDP binding in brown adipose tissue (BAT) of fenfluramine-treated rats. To further investigate a possible involvement of BAT in the drug's metabolic effects, 113Sn-labelled microspheres were injected into the left cardiac ventricle of conscious rats 70 80 min after intraperitoneal delivery of 20 mg/kg fenfluramine (DL-mixture) or saline vehicle. At 28 degrees C ambient temperature, fenfluramine augmented resting whole-body VO2 and increased the microsphere entrapment in BAT, indicating enhanced blood flow and metabolism. At 20 degrees C ambient temperature, the expected increase in BAT blood flow associated with nonshivering thermogenesis was observed in control rats, but in fenfluramine-treated rats the increase in BAT blood flow was severely attenuated, and VO2 and body temperature were reduced. The stimulatory effect of fenfluramine on BAT metabolism was not prevented by urethane anesthesia but did not occur if the tissue was denervated. These blood flow measurements corroborate previous reports, based on GDP-binding assays, that fenfluramine treatment can augment thermogenesis in BAT by effects mediated through the innervation of the tissue. However, the data also indicate that this calorigenic effect is dependent on ambient temperature being near thermoneutrality and that in a cool environment the drug inhibits BAT thermogenesis. PMID- 1521179 TI - Conopressin G, a molluscan vasopressin-like peptide, alters gill behaviors in Aplysia. AB - Superfusion of an invertebrate vasopressin structural analogue, conopressin G, over the abdominal ganglion of an in vitro preparation of Aplysia californica has significant neurophysiological and behavioral effects. Both the amplitude of the siphon-evoked gill withdrawal reflux and concomitant activity in gill motor neurons are reduced in the presence of conopressin G. Moreover, the frequency of spontaneous gill movements and their neural correlate, interneuron II activity, are increased. These behavioral modifications strongly resemble those that occur during the food-aroused behavioral state in intact Aplysia. In addition, conopressin G superfusion reduces both the excitability of gill motor neurons and the strength of gill contractions in response to gill motor neuron discharges elicited by direct depolarizing current. A role for conopressin G or a similar peptide in the modulation of gill behaviors associated with the food-aroused state is suggested. PMID- 1521180 TI - Rat atrial muscle responses with caffeine: dose-response, force frequency, and postrest contractions. AB - Caffeine has been reported to have a positive and (or) a negative inotropic effect on cardiac muscle. In this study, the force-frequency and postrest characteristics of rat atrium were studied in the presence of caffeine (1.0-10 mM) to see if the interval between beats affected the response of cardiac muscle to caffeine. When stimulation frequency was 0.5 or 2.0 Hz, there was a positive followed by a negative inotropic response with 1, 5, or 10 mM caffeine. Incomplete relaxation occurred under these circumstances, giving rise to contracture. At low frequency of stimulation (0.1 Hz) caffeine had only a negative inotropic effect, and this effect was greater with 1 mM caffeine than with 5 mM caffeine. In the absence of caffeine, when stimulation at 0.5 or 3 Hz was interrupted, a pause of 2-20 s resulted in potentiation. When caffeine was present (2.0 mM), postrest potentiation was severely attenuated, but the steady state contraction amplitude within the range 0.5-3.0 Hz was not different. These results are consistent with the hypothesis that caffeine induces a leak of Ca2+ from the sarcoplasmic reticulum, and this Ca2+ is extruded from the cell, possibly by Na+/Ca2+ exchange. Sarcoplasmic reticular uptake of Ca2+ and the translocation to release sites appear not to be affected by caffeine within 1-5 mM concentrations. PMID- 1521181 TI - Excitability of canine colon circular muscle disconnected from the network of interstitial cells of Cajal. AB - The 6 cpm omnipresent slow waves recorded in the circular muscle (CM) layer of canine colon are generated at the submucosal surface of the CM layer. After removal of the submucosal network of interstitial cells of Cajal (ICC), 66% of the CM preparations (25 of 38) were quiescent in Krebs solution. In the presence of carbachol, seven of nine of these spontaneously quiescent CM preparations demonstrated slow wave-like activity with mean frequency, duration and amplitude of 5.9 +/- 0.4 cpm, 2.8 +/- 0.5 s, and 0.8 +/- 0.2 mV, respectively. Similar slow wave-like activities were induced by TEA (seven out of eight quiescent CM preparations) with frequency, duration and amplitude of 6.1 +/- 0.2 cpm, 2.7 +/- 0.5 s, and 1.0 +/- 0.2 mV, respectively, and by BaCl2 (eight of eight quiescent CM preparations) with frequency, duration, and amplitude of 6.3 +/- 0.3 cpm, 1.8 +/- 0.2 s, and 0.5 +/- 0.1 mV, respectively. All the induced activities were abolished in the presence of 1 microM D600. CM preparations with the submucosal ICC network intact (ICC-CM) showed slow wave activity in Krebs solution at a frequency of 6.2 +/- 0.2 cpm, a duration of 3.6 +/- 0.2 s, and an amplitude of 1.0 +/- 0.1 mV (n = 22). When ICC-CM preparations were stimulated by BaCl2, carbachol, or TEA, the slow wave frequency did not change significantly, but the duration increased as well as the amplitude. In the presence of D600, the upstroke of slow waves remained and the frequency was not affected.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1521182 TI - Effect of pressure on circumferential order of adventitial collagen in human brain arteries. AB - A key factor in the contribution of collagen fibres to tissue mechanics is the alignment of the fibres, which we studied in brain arteries, focussing on alignment changes with distending pressure. Arteries from autopsy were cannulated and fixed at different distending pressures from 0 to 200 mmHg (1 mmHg = 133.32 Pa), alcohol dehydrated, paraffin embedded, sectioned, and stained for birefringent enhancement. The polarized light microscope was set for extinction and fibre orientations were precisely determined at the rotational position of extinction for 200 positions around the artery wall. Results from 22 arterial cross sections revealed, with fixation pressure, a significant but incomplete straightening of collagen (even at 200 mmHg). The mean angular deviation of alignment of fibres was +/- 30 degrees for arteries fixed at zero transmural pressure, which in contrast was +/- 7 degrees for the inner and +/- 13 degrees for the mid-adventitia for arteries fixed at 200 mmHg transmural pressure. We verified on vessels fixed at low pressure, by using a full wave plate in conjunction with the specificity of the interference colours, that the measurements were correct and not confused with angles at 90 degrees to the morphological axis. Alternative tissue processing was done with two arteries fixed at 120 mmHg and processed for frozen sections; the results showed diminished variability in alignment but within the range of measurements for wax embedded tissue. We concluded that the collagen fabric could contribute to the mechanics of brain arteries but that it would be with sinusoidal rather than straightened fibres of collagen. PMID- 1521183 TI - Glibenclamide depresses the slowly inactivating outward current (ID) in hippocampal neurons. AB - Sulphonylurea drugs, such as glibenclamide and tolbutamide, are widely used as selective blockers of adenosine triphosphate-sensitive K channels. In experiments on hippocampal slices (from Wistar rats) glibenclamide (and possibly gliquidone and tolbutamide) significantly reduced the highly voltage-dependent, 4 aminopyridine-sensitive D-type outward current of CA3 neurons. Judging by these observations, the sulphonylureas may not be as selective as generally believed. PMID- 1521184 TI - Direct evidence for nitric oxide formation from glyceryl trinitrate during incubation with intact bovine pulmonary artery. AB - It has been proposed that the mechanism of the vasodilator action of glyceryl trinitrate (GTN) involves biotransformation to nitric oxide. A sensitive chemiluminescence method for nitric oxide determination was used to test this hypothesis. In four experiments, bovine pulmonary artery (BPA) was incubated with GTN (0.1 mM) in Krebs' solution (2 mL) containing 30 mM KCl, and in anaerobic conditions using 95% Ar - 5% CO2, in a sealed micro-Fernbach flask (6.2-mL volume). After incubation for 2, 5, 10, or 20 min at 37 degrees C, 400-microL aliquots of headspace gas were removed and injected into a redox chemiluminescence detector. Nitric oxide formation was first measurable at 5 min (76 +/- 53 pmol/g wet wt. BPA), and increased with incubation time (174 +/- 46 pmol/g wet wt. BPA after 10 min and 310 +/- 67 pmol/g wet wt. BPA after 20 min). This is the first direct chemical measurement of nitric oxide formation during interaction of GTN with vascular smooth muscle. These data support the concept that GTN is a nitrovasodilator prodrug acting via the formation of nitric oxide. PMID- 1521185 TI - Epiphytic populations of Pseudomonas syringae on barley. AB - The epiphytic populations of Pseudomonas syringae were monitored on 23 barley entries planted in the field in four replications during the summer of 1986, and on six selected entries during the summer of 1987, from the second-leaf stage until senescence. Populations were initially low (0-3 log colony-forming units (cfu) per leaf) in all but one entry; they generally increased throughout the season, and at the end they reached 3-7 log cfu/leaf. Significant differences among the average epiphytic populations were found in the 1986 trial; only one entry, however, had a significantly different average population in the 1987 trial. The slopes of population increase were also compared: significant differences were observed in 1986 but not in 1987. In addition to epiphytic population counts, the percentage of ice nucleation active bacteria was determined in the population isolated from each leaf sample, and averaged throughout the season for each entry. Significant differences were observed in 1986 and in 1987. When the entries were ranked according to their average epiphytic population and compared between the two experiments, they were found to be very similar. The same was not true for the other parameters studied in the experiment. PMID- 1521186 TI - Evaluation of filamentous fungi isolated from petals of bean and rapeseed for suppression of white mold. AB - The influence of filamentous fungi isolated from petals of bean and rapeseed on white mold caused by Sclerotinia sclerotiorum was evaluated. In laboratory trials, macerates of agar plugs containing hyphal fragments of the pathogen in combination with individual fungi were applied onto celery petioles, and subsequent lesion diameters were recorded. The efficacy of 10 fungi exhibiting a spectrum of lesion suppression on celery was correlated with the efficacy of the same fungi in growth-room (r = 0.78, P = 0.005) and greenhouse (r = 0.68, P = 0.032) trials. From 315 isolates of fungi evaluated in the laboratory trials, the 10 most suppressive isolates were selected and evaluated in growth-room trials. Spores of the test fungi were applied onto flowers simultaneously with, and up to 24 h after, inoculation with ascospores of S. sclerotiorum. The most suppressive fungi included isolates of Alternaria alternata, Drechslera sp., Epicoccum purpurascens, Fusarium graminearum, Fusarium heterosporum, and Myrothecium verrucaria. These fungi did not provide consistent control of white mold of bean in a field test repeated four times in 1988. However, Drechslera sp. and E. purpurascens significantly reduced the incidence of white mold in one and two trials, respectively. Combination treatments of A. alternata and Benlate (1.1 kg active ingredient ha-1) suppressed white mold significantly more than either treatment alone in one of four trials. PMID- 1521187 TI - Effects of culture conditions on the in vitro infection of fibroblasts by Candida albicans. AB - The effects of yeast culture age, carbon source, growth temperature, and germ tube inducers on adherence to primary fibroblast cultures was studied in conjunction with the determination of adherence-mediated mammalian cell damage by measuring chromium-51 release from fibroblast monolayers. The results indicated that yeast culture age affected adherence only when the yeasts were grown at 37 degrees C, not after growth at 28 degrees C. At 37 degrees C, quantitatively fewer exponential-phase, glucose- or galactose-grown yeasts adhered to fibroblasts than did yeasts that were in lag or stationary phases. The reduced adherence correlated with less chromium-51 release and reduced germ-tube formation. The addition of germ-tube inducers, such as N-acetyl-D-glucosamine or serum, to exponential-phase yeasts caused an increase in germ-tube formation with a concomitant increase in yeast adherence and release of chromium-51 from the monolayers. Exponential-phase galactose-grown yeasts were more responsive to serum-induced germ-tube formation, germ-tube elongation, and fibroblast adherence than were exponential-phase glucose-grown yeasts. In addition, exponential-phase galactose-grown yeasts caused more chromium-51 release from monolayers in the presence of serum than did glucose-grown yeasts. Overall, conditions that enhanced germ-tube formation and elongation resulted in greatest adherence mediated damage to the monolayers. PMID- 1521188 TI - Localization of a 210-kDa microtubule-interacting protein in the yeast Saccharomyces cerevisiae. AB - Using the monoclonal antibody MA-01, which recognizes a 210-kDa protein in cell free extracts, spindle and cytoplasmic microtubules were visualized in budding yeast, Saccharomyces cerevisiae. In additional, a spot-like staining was found beneath the plasma membrane, revealing in part correlation with F-actin distribution. This pattern was common for cells of all cell-cycle stages. The interaction of the protein recognized by MA-01 with microtubules was confirmed in the double labeling with a polyclonal antitubulin antibody and by the sensitivity of intranuclear structures stained by MA-01 to the microtubule disrupting drug nocodazole. PMID- 1521189 TI - Purification of an enterotoxin produced by Bacillus cereus by immunoaffinity chromatography using a monoclonal antibody. AB - A murine monoclonal antibody (MAb) with high reactivity to an enterotoxin produced by Bacillus cereus was used to prepare an immunoadsorbent for purification of the enterotoxin. By immunoaffinity chromatography using the immunoadsorbent, approximately 25% of crude enterotoxin applied was recovered in the eluate. The purified enterotoxin was found to be electrophoretically and antigenically homogeneous. It also showed vascular permeability activity and mouse lethality, and caused fluid accumulation in mouse ligated intestinal loops, whereas it did not show any hemolytic and lecithinase activities. Thus, immunoaffinity chromatography proved useful in the purification of enterotoxin produced by B. cereus in terms of recovery, purity, and relative ease of performing the purification. PMID- 1521190 TI - Competition among Rhizobium leguminosarum bv. phaseoli strains for nodulation of common bean. AB - Six effective Rhizobium leguminosarum bv. phaseoli strains were examined for nodulation competitiveness on common bean (Phaseolus vulgaris L.), using all possible two-strain combinations of inoculum. Nodule occupancy was determined with strain-specific fluorescent antibodies. The strains were divided into three groups according to their overall competitive abilities on pole bean cv. Kentucky Wonder and bush bean cv. Bountiful. Strains TAL 182 and TAL 1472 were highly competitive (greater than 70% nodule occupancy); strains KIM-5, Viking 1, and CIAT 899 were moderately competitive (approximately 50% nodule occupancy); and strain CIAT 632 was poorly competitive (less than 5% nodule occupancy). The competitiveness of the six strains was similar on the two host cultivars. The proportion of competing strains in the inoculum influenced the nodule occupancy of the highly competitive and moderately competitive strains, but not that of the poorly competitive strain. Two outstanding strains (TAL 182 and TAL 1472) were identified as ideal model strains for molecular and genetic studies on nodulation competitiveness. PMID- 1521191 TI - Plasmids in Listeria monocytogenes and other Listeria species. AB - One hundred and twenty-two food, clinical, and veterinary strains of Listeria monocytogenes were examined for the presence of plasmids. Twenty-five (20%) contained plasmids, which varied from 1.3 to 66 MDa in size. Of 10 strains of other Listeria species (L. innocua, L. ivanovii, L. welshimeri, L. seeligeri, L. grayi, and L. murrayi) examined, seven (70%) contained plasmids, varying from 38 to 53 MDa. No strains with multiple plasmids were found. Plasmids of identical size were isolated from related strains in some, although not all, cases. The presence of a plasmid in a strain was not related to phenotypic characters of known extrachromosomal inheritance. PMID- 1521192 TI - O-acetylated peptidoglycan: its occurrence, pathobiological significance, and biosynthesis. AB - Bacterial cell walls and their structural units, particularly peptidoglycan, induce a vast variety of biological effects in host organisms. The pathobiological effects of peptidoglycan are greatly enhanced by various modifications and substitutions to its basic composition and structure. One such modification is the presence of acetyl moieties at the C-6 hydroxyl group of N acetylmuramyl residues, and to date, 11 species of eubacteria, including some important human pathogens, such as Neisseria gonorrhoeae, Proteus mirabilis, and Staphylococcus aureus, are known to possess O-acetylated peptidoglycan. This review addresses the influence of O-acetylation of peptidoglycan on its resistance to degradation both in vitro and in vivo, the clinical importance of the modification, and the currently held views on the pathway for its biosynthesis. PMID- 1521193 TI - Laboratory investigation of virulence among strains of Yersinia enterocolitica and related species isolated from pigs and pork products. AB - Eighty strains of Yersinia enterocolitica and related species isolated from slaughtered pigs and pork products were tested for possession of virulence associated phenotypes by employing 12 in vivo and in vitro assays. The isolates could be broadly divided into two groups: (i) strains belonging to pathogenic bioserotypes of Y. enterocolitica that displayed virulence-associated characteristics in most or all assays and (ii) strains belonging to Y. enterocolitica biotype 1A and to related species that were largely negative in these assays. No individual test was found as a single reliable measure of virulence. All strains belonging to Y. enterocolitica serotype O:1,2,3 were pyrazinamidase positive (indicates avirulence) and autoagglutination negative but were positive in all other virulence assays. Salt aggregation was found to be a better indicator of virulence than latex particle agglutination, both of which measure surface hydrophobicity. Overall, tissue culture cell invasion provided the best selection of a subpopulation of yersiniae that are potentially virulent. However, crystal violet and Congo red binding assays among others provided good prediction of virulence at the time of testing. Our results provide further evidence that swine may constitute an important reservoir of human pathogenic strains. PMID- 1521195 TI - Ethics and the physician. PMID- 1521196 TI - Ethics and the physician. PMID- 1521194 TI - Growth morphology of Streptomyces akiyoshiensis in submerged culture: influence of pH, inoculum, and nutrients. AB - Most media in which the growth of shaken submerged cultures of Streptomyces akiyoshiensis was examined did not support the formation of well-dispersed mycelial suspensions. Investigation of the culture conditions promoting dispersed growth showed the pH of the culture medium to be of critical importance; an initial value of 5.5 minimized aggregation of the mycelium while supporting adequate biomass production. In cultures started at this pH, spore inocula gave better mycelial dispersal than did vegetative inocula; with spore inocula, growth morphology was also less affected by inoculum size. The composition of the nutrient solution influenced the extent of mycelial dispersal; slow growth was often associated with clumping but no clear correlation was observed between pellet formation and the ability of carbon or nitrogen sources to support rapid growth. Increasing the phosphate concentration from 0.5 to 15 mM caused a modest decrease in mycelial aggregation. Conditions promoting a well-dispersed mycelium suitable for studying the physiological control of secondary metabolism also supported the formation of 5-hydroxy-4-oxonorvaline by S. akiyoshiensis. PMID- 1521197 TI - Ethics and the physician. PMID- 1521198 TI - Ethics and the physician. PMID- 1521199 TI - Whose responsibility are insurance forms? PMID- 1521200 TI - To glove or not to glove. PMID- 1521201 TI - To glove or not to glove. PMID- 1521202 TI - In support of breast-feeding. PMID- 1521203 TI - Drug information discrepancy. PMID- 1521204 TI - Phases in a drug's use. PMID- 1521205 TI - Family doctors consult with specialists for nonmedical reasons. PMID- 1521206 TI - Four decades of glucocorticosteroid immunosuppression. PMID- 1521207 TI - Toward integrated medical resource policies for Canada: 8. Geographic distribution of physicians. PMID- 1521208 TI - Periodic health examination, 1992 update: 2. Routine prenatal ultrasound screening. Canadian Task Force on the Periodic Health Examination. PMID- 1521209 TI - Nancy B.: the criminal code and decisions to forgo life-sustaining treatment. PMID- 1521210 TI - Low-dose steroid therapy in cyclosporine-treated renal transplant recipients with well-functioning grafts. The Canadian Multicentre Transplant Study Group. AB - OBJECTIVE: Low-dose prednisone given on alternate days as a steroid adjunct to cyclosporine therapy was investigated primarily for its influence on kidney graft and patient survival and, secondarily, on renal function and complications. DESIGN: Multicentre randomized double-blind clinical trial. SETTING: Fourteen Canadian transplant centres. PATIENTS: A total of 523 patients with well functioning renal transplants (cadaveric grafts or grafts from living related donors) and without active graft rejection reactions who were entered into the trial from 1982 to 1985. INTERVENTION: Patients were randomly assigned 90 days after transplantation to receive either placebo (260 patients) or low-dose prednisone (263 patients). MAIN OUTCOME MEASURES: Graft and patient survival. MAIN RESULTS: After at least 5 years of follow-up 50 patients assigned placebo had lost their graft and 17 had died; the corresponding figures for those assigned prednisone were 38 and 16. After an average interval of 1.4 years 143 patients in the placebo group and 123 patients in the prednisone group had stopped therapy with the test drug or had had their treatment group decoded or both. Patients were withdrawn from the study 2 years after stopping the test therapy. The actuarial 5-year graft survival rates were 73% and 85% in the placebo and prednisone groups respectively (p = 0.03), and the actuarial 5-year patient survival rates were 92% and 94% respectively (p = 0.6). This analysis included 43 and 29 graft losses and 14 and 12 deaths in the placebo and prednisone groups respectively. Weibull parametric modelling of graft survival identified the following variables as risk factors for graft loss: histocompatibility leukocyte antigen B (HLA-B) mismatching (p = 0.007), donor death from cerebrovascular accident (p = 0.01), increased donor age (p = 0.02) and being a male recipient (p = 0.05). When these factors were included in the Cox proportional hazards model, the influence of assigned treatment on graft survival was reduced to p = 0.1. Donor death from cerebrovascular accident (p = 0.002), diabetes mellitus in the recipient (p = 0.02) and increased recipient age (p = 0.05) were risk factors for patient death. Renal function and incidence of complications were similar in the treatment groups. CONCLUSIONS: Continued administration of low-dose prednisone on alternate days is advisable, particularly in patients with cadaveric grafts and those with previously failed transplants. PMID- 1521211 TI - Effect of nonmedical factors on family physicians' decisions about referral for consultation. AB - OBJECTIVES: To identify nonmedical factors perceived by family physicians (FPs) and consultants as important influences on decisions about referral for consultation, to determine the relative frequency with which such factors are cited and to identify those factors ranked as most important by the FPs and consultants. DESIGN: Survey with semistructured interview between July 1989 and April 1990. PARTICIPANTS: A total of 41 FPs and 20 consultants who were practising or had practised previously in Nova Scotia. INTERVENTIONS: The questionnaire comprised 10 questions: 4 were nondirective "probes" designed to elicit responses without suggesting possible answers, 2 asked the participants to rank such responses in order of importance, and 4 were "prompts" that asked for comments about a list of factors based on a review of the literature. RESULTS: A total of 4845 discrete items were mentioned as being capable of influencing FPs' decisions about referral for consultation. Aggregation of related items resulted in a list of 35 nonmedical factors, of which 11 were identified by at least half the respondents and 14 by less than half but more than 10. These 25 factors fell into three categories: patient and family factors (e.g., patient's wishes), FP and consultant factors (e.g., FP's capabilities), and other influences (e.g., style of practice). On the basis of both frequency of identification and priority scores "patient's wishes" emerged as the most important factor. Two medical factors that were consistently cited--type of problem and age of patient--were thought to interact with the other factors. CONCLUSION: Certain nonmedical considerations may substantially affect physicians' referral practices. PMID- 1521212 TI - Inadvertent intracranial placement of a nasogastric tube in a patient with severe head trauma. PMID- 1521213 TI - Statement on influenza vaccination for the 1992-93 season. PMID- 1521214 TI - Diabetes mellitus. 1912. PMID- 1521216 TI - Ottawa's meningococcal outbreak provided a lesson in professional judgement and science. PMID- 1521215 TI - Clinical practice guidelines for treatment of diabetes mellitus. Expert Committee of the Canadian Diabetes Advisory Board. PMID- 1521217 TI - Cases of MD-instigated billing fraud rare but governments watch closely for "irregularities". PMID- 1521218 TI - Recession has taken more than an economic toll, physicians report. PMID- 1521219 TI - Calgary's Standardized Patient Program appears to be the wave of the future. PMID- 1521220 TI - Challenge the accepted doctrine on HIV-AIDS link, science writers told. PMID- 1521221 TI - MD-patient communication key to reducing asthma's toll, seminar told. PMID- 1521222 TI - Breast implant controversy much ado about very little, plastic surgeons say. PMID- 1521223 TI - Enhanced expression of stomach cancer antigen derived from malignantly transformed bloom syndrome cells previously labeled with bromodeoxyuridine. AB - Bromodeoxyuridine (BrdU) greatly enhanced expression of stomach (ST) cancer antigen (CA) that originated from a malignantly transformed Bloom syndrome (BS) cell line (BS-SHI-4M), although the expression was suppressed with a decrease in sister chromatid exchange (SCE) in the presence of deoxythymidine (dT) or deoxycytidine (dC) and enhanced with an increase in SCE with deoxyguanosine (dG) or deoxyadenosine (dA). Although the exact mechanisms for enhancing CA by BrdU treatment are unknown, these findings appeared to be of special interest because of the parallelism of CA expression and SCE alterations. The finding that BrdU enhancement of the ST CA was effective not only in the immunofluorescence (IF) protocol but also in the band appearance of Western blotting would be worthwhile as a sensitive serodiagnosis of cancer. The 118-kd band obtained from proteins of ST CA cells previously labeled with BrdU was clearly more darkly stained than that from nonlabeled cells and enabled eight weak-positive ST CA to show strong positive levels retaining complete negativity to nonmalignant sera. Some ST cancer sera (advanced cancer), which originally gave a negative reaction in the nonlabeled condition, still inhibited negative reaction even in BrdU-labeled ST CA cells, however. The inability to detect cancer antibody in our assay might be due to immunocomplexes. Acid dissociation and ultrafiltration of sera from six of seven advanced ST cancers (originally IF negative) have allowed detection of antibody responses to ST CA by Western blot assay with enhanced reactivity as compared with the negativity under native serum conditions. This technique provides a reasonable avenue for study of the mechanisms of CA expression and serodiagnosis. PMID- 1521224 TI - Two karyotypically unrelated clones with the t(5;17) and deletion of 5q in myelodysplastic syndrome. AB - We report a patient with primary myelodysplastic syndrome (MDS) and two coexisting karyotypically independent clones. Cytogenetic investigation of bone marrow (BM) cells at diagnosis showed, besides the cells with normal karyotype, a clone that manifests an interstitial deletion of the long arm of chromosome 5 and a second one with a t(5;17). The rarity of finding a BM mosaicism in myelodysplasia with 5q- in some cells and different chromosomal abnormalities in others may be considered to support the multistep theory of pathogenesis in MDS. PMID- 1521226 TI - Mitotic spindle failure in human cancer. PMID- 1521225 TI - A case of lipoblastoma with t(3;8)(q12;q11.2). AB - We studied a single case of lipoblastoma in a 4-year-old boy. Cytogenetic analysis of the tumor cells showed two abnormal clones: 47,XY,t(3;8)(q12;q11.2),+mar, and 46,XY,t(3;8)(q12;q11.2). To our knowledge, this is the second report of chromosome findings in this rare tumor. Although lipoblastomas are frequently confused with myxoid liposarcomas, breakpoints in our patient were different from those of myxoid liposarcoma. PMID- 1521227 TI - Complex karyotype including trisomy 8 in a case of B-chronic lymphocytic leukemia. PMID- 1521228 TI - The activated human c-Ha-ras-1 oncogene as a mutagen. AB - The induction of gene mutations and chromosome aberrations by plasmid pEJ6.6 carrying the activated c-Ha-ras-1 oncogene from human bladder carcinoma was studied in cultured Chinese hamster cells. Both an increase in the frequency of hypoxanthine-phosphoribosyltransferase-deficient (HPRT-) mutants and chromosome aberrations was observed after pEJ6.6 transfection as compared to control series (pBR322). In order to define whether it is the oncogene which is responsible for the mutagenic effect of pEJ6.6, a derivative of c-Ha-ras-1 carrying a deletion in its coding region was constructed. As shown in all experiments, the frequency of HPRT- mutants after treatment with pEJ6.6 plasmid exceeded that in control dishes treated by pEJ6.6 plasmid with an inactivated oncogene. The effect was rather weak but statistically significant. Thus, the results of experiments carried out show that the mutagenic activity of pEJ6.6 plasmid is chiefly determined by its oncogene. The role of the mutagenic effects of activated oncogenes in malignant transformation is discussed. PMID- 1521229 TI - Chromosome number correlates with survival in patients with malignant pleural mesothelioma. AB - Modal (MO) and mean (ME) chromosome numbers determined by cytogenetic analysis were compared with survival in 34 patients with diffuse malignant pleural mesothelioma. The patients with normal chromosome number and no clonal abnormalities (MO = 46) survived longer (median survival 17 months) than patients with clonal abnormalities. MO greater than 46 correlated with shorter survival (median 12 months) (p = 0.0186). The correlation was more clear between mean chromosome number (ME) and survival: the median survival of patients with ME greater than 46 was 13 months whereas that of the patients with ME less than 46 was 26 months and ME = 46 (normal chromosome number and no clonal abnormalities) 31 months (p = 0.0007). Furthermore, there was a tendency of an association between ME = 46, ME less than 46 and epithelial subtype reported to be associated with a favorable prognosis in mesothelioma. The addition of chromosome material may present a mechanism to enhance expression of genes important in the pathogenesis of mesothelioma and lead to more aggressive behavior of the tumor. PMID- 1521230 TI - Cytogenetic biclonality in malignant hematologic disorders. AB - Generally, malignant hematologic disorders have been believed to be of monoclonal origin. However, cytogenetically unrelated clones have been reported in some disorders including one case of acute leukemia (AL), one of acute lymphoblastic leukemia (ALL), one of acute myeloblastic leukemia (AMMoL), and five of myelodysplastic syndromes (MDS). The most frequent chromosome abnormality was trisomy 8 (75%), followed by trisomy 21 (37.5%, including tetrasomy 21) and trisomy 11 (25%). Two patients showed both trisomy 8 and 11, one also had trisomy 21 (triclonal). One patient showed two cytogenetically distinctive clones in which one was 47,XY,+8, related to myeloid cells, and the other had a del(6q) and del(9p), suggesting lymphoid cells. One patient we report and 5 from the literature had two unrelated clones with trisomy 8 and deletion of the long arm of chromosome 5 (5q-); all had MDS. Review of our records showed that 11 patients with both trisomy 8 and 5q- in the same abnormal karyotype (not biclonal) had AL, i.e., 10 of acute nonlymphocytic leukemia (ANNL) and one of chronic myelogenous leukemia (CML) in blastic crisis. These findings suggest that cytogenetically unrelated clones may indicate hematopoietic biclonality. PMID- 1521231 TI - Uterine leiomyoma cytogenetics. III. Interphase cytogenetic analysis of karyotypically normal uterine leiomyoma excludes possibility of undetected trisomy 12. AB - Uterine leiomyoma, a benign tumor that histopathologically is rather homogeneous, was recently characterized cytogenetically. About 40% of the investigated tumors are associated with clonal chromosome abnormalities and five different subgroups have been identified, characterized by trisomy 12, t(12;14)(q14-15;q23-24), del(7q), t(1;2)(p36;p24), and 6p rearrangements. In our survey of 76 cases, trisomy 12 was observed in 10% of the abnormal cases. To exclude a possible underscoring of this abnormality, we reexamined 15 of the cases with normal karyotype by interphase cytogenetics using a chromosome 12 alphoid DNA probe. PMID- 1521232 TI - Recurrent chromosome aberrations in abdominal smooth muscle tumors. AB - Short-term cultures of four abdominal smooth muscle tumors, three leiomyosarcomas and one leiomyoma, were analyzed cytogenetically. A low-grade malignant, epithelioid leiomyosarcoma had a normal karyotype. The other two leiomyosarcomas had abnormal karyotypes; one was near-diploid, and the other was near-triploid. Structural rearrangements of the short arm of chromosome 16 and monosomies of chromosomes 14, 15, and 22 were observed in both tumors. When our cases and previously published abdominal leiomyosarcomas are viewed in conjunction, loss of chromosomes 14, 15, and 22 are the most frequent abnormalities. The leiomyoma, the second cytogenetically abnormal nonuterine leiomyoma reported to date, had a hyperdiploid karyotype with a chromosome number of 56 and structural rearrangements of chromosomes 9, 14, and 19. The only aberrations similar to those observed in the previously reported esophageal leiomyoma were trisomies of chromosomes 7 and 8. PMID- 1521233 TI - Deletion 12p in de novo acute myeloid leukemia. An association with early progenitor cell. AB - Deletion of the short arm of chromosome 12 as the sole karyotypic abnormality was found in three cases of acute myeloblastic leukemia (AML). In contrast to what has previously been reported in the literature, none of our cases had an antecedent history of myelodysplasia or toxic exposure, and basophilia was absent. Two cases were terminal deoxynucleotidyl transferase (TdT) positive, suggesting involvement of an early progenitor cell. PMID- 1521234 TI - Ring chromosome in parosteal osteosarcoma. Clinical and diagnostic significance. AB - In this study, two specimens of a parosteal osteosarcoma, a rare primary bone neoplasm comprising only 3-6% of all osteosarcomas, were cytogenetically analyzed utilizing standard techniques. In contrast to the complex karyotypes previously reported in osteosarcoma, this particular histologic subtype was characterized by a single chromosomal aberration, a ring chromosome. Ring chromosomes have been described as characteristic for two other low-grade malignant mesenchymal neoplasms, well-differentiated liposarcoma and dermatofibrosarcoma protuberans. We propose that the observation of a ring chromosome in osteosarcoma also correlates with a low-grade malignant potential. PMID- 1521235 TI - Sister chromatid exchange and chromosome breakage in complete hydatidiform moles. AB - Women with complete hydatidiform moles (CHM) are at a 10% risk for developing persistent trophoblastic disease or choriocarcinoma. We studied sister chromatid exchange (SCE) as a prognostic indicator for malignancy in peripheral blood lymphocytes (PBL) from women with CHM and their husbands, but found no differences from normal control couples. SCE levels in cultured tissue derived from 11 CHM (avg. 7.9) and 2 choriocarcinomas (avg. 6.8) were not significantly different from those of 8 normal skin fibroblast cultures (avg. 7.8). These same tissues were then examined for chromosome breakage which was significantly higher for CHM (0.48/cell) and choriocarcinoma (0.87/cell) than normal fibroblasts (0.33/cell). Chromosome breaks occurred at 50-60% known fragile sites and at 50 55% of cancer breakpoints. Whereas SCE was only associated with 13% of breaks in the three tissues, half of these were at known fragile sites. Our results suggest that SCE is not an indicator of malignancy in PBL or cultured cells from CHM or choriocarcinoma and that the level of SCE is not elevated in CHM or choriocarcinoma. However, our results confirm the increased breakage seen in the latter two tissues which may represent general DNA instability predisposing to choriocarcinoma and its accompanying chromosomal rearrangements. PMID- 1521236 TI - Genetics and biology of human ovarian teratomas. III. Cytogenetics and origins of malignant ovarian germ cell tumors. AB - This report presents cytogenetic data on three cases of malignant ovarian germ cell tumors. All were diagnosed as malignant teratoma; case 1 with yolk sac elements; case 2 with elements of endodermal sinus tumor, embryonal carcinoma, and choriocarcinoma; and case 3 with yolk sac elements and embryonal carcinoma. Metaphase cells from each tumor, and normal tissue from the host, were karyotyped and scored for centromeric heteromorphisms in an attempt to determine the mechanism of origin. The karyotypes were 79,XXX,+1,+3,-6,+8,+12,+14,-15,+17, +20,+21,+22;49,XX,+8,+12,+22; and 48,XX,+3,+14, respectively. The analysis of centromeric heteromorphisms and DNA fingerprints of host and teratoma using the M13 probe revealed that one case originated from a germ cell before the first meiotic division. Normal host tissue was not available in case 2, but several centromeric markers were heterozygous in the tumor, indicating either meiosis I error or complete failure of germ cell meiosis. In the third case the centromeric heteromorphisms that were heterozygous in the host appeared to be homozygous for certain chromosomes and heterozygous for others in the tumor. These results suggest that germ cell teratomas could arise by the fusion of two ova. PMID- 1521237 TI - Cell-cycle progression rates and sister chromatid exchange frequencies in the bone marrow of patients with myelodysplastic syndrome and acute myeloid leukemia. AB - The proliferation characteristics of leukemic cells may be a determining factor in disease course and response to therapy. The present study compares the rate of cell-cycle progression in the bone marrow of 16 hematologically normal subjects, 19 patients with acute myeloid leukemia (AML), and 23 patients with myelodysplastic syndrome (MDS). The frequency of sister chromatid exchanges (SCE) in bone marrow cells is also compared. MDS and AML patients showed a reduction in the rate of cell-cycle progression compared with normal subjects. Patients with 'high risk' MDS (RAEB/RAEB-t) did not differ significantly from patients with AML but had a significantly slower rate of cell-cycle progression than patients with 'low-risk' MDS (PASA/RA). There was no correlation between the rate of cell-cycle progression and clonal karyotype status or the percentage of blast cells in either MDS or AML. There were no significant differences in SCE frequency between normal subjects and MDS or AML patients. PMID- 1521238 TI - Trisomy of chromosome 8 in myelodysplastic syndrome. Significance of the fluctuating trisomy 8 population. AB - Chromosome analyses were performed in five patients with myelodysplastic syndrome (MDS) who showed trisomy of chromosome 8 during the course of their disease. Four of these patients showed trisomy 8 at the diagnosis of MDS, and the remaining one had trisomy 8 when the leukemia phase developed. The proportion of bone marrow (BM) cells with trisomy 8 in the four patients who showed trisomy 8 at MDS diagnosis fluctuated, and this fluctuation was not related to the percentage of blasts in the BM or to progression of the disease. However, in two patients, metaphase cells with trisomy 8 disappeared when their anemic state improved, although leuko-thrombocytopenia was still present, suggesting that the decrease in the number of BM cells with trisomy 8 reflects hematologic features in some MDS patients. These findings indicate that trisomy 8 in our MDS patients was possibly not the primary event in the genesis of the disease, and that there may have been competition between a normal karyotype clone and a trisomy-8-positive clone. Our results further suggest that the presence of a clone with trisomy 8 is not always a sign of disease progression or of poor prognosis in MDS patients. PMID- 1521239 TI - Clinical significance of the del(20q) chromosome in hematologic disorders. AB - Patients with hematologic neoplasias often have chromosomal aberrations in the cells of their bone marrow or unstimulated blood. One recurrent abnormality is a deletion of the long arm of chromosome 20, primarily described in polycythemia vera, but later seen in a range of hematologic disorders. We have studied 32 patients with del(20q) as the sole chromosomal aberration, investigating significance of this aberration for the clinical diagnoses, hematologic parameters, and prognoses within this patient group. According to our results, del(20q) is primarily associated with myeloid disorders, but it is not specific for any certain disease, nor does the proportion of cells with del(20q) correlate with prognosis. PMID- 1521240 TI - Specific chromosomal aberrations correlated to transformation in Chinese hamster cells. AB - Cytogenetic changes were investigated during the spontaneous progression of CHEF18 Chinese hamster cells towards tumorigenicity. We further report the chromosomal characterization of a series of spontaneous anchorage-independent clones, as well as of a series of tumor-derived cell lines resulting from injection of late passage cells in nude mice. The high karyotypic homogeneity (presence of four marker chromosomes strictly associated in all the metaphases analyzed) in all clones and tumor-derived cell lines prompted us to alter the specific pattern of chromosomal aberrations in order to identify which if any of the aberrations were more strictly related to transformation. For this purpose we treated a tumor-derived cell line with Colcemid and analyzed the reversion of anchorage-independent phenotype in the subclones showing an altered association of the four marker chromosomes. We conclude that two of four marker chromosomes contribute to anchorage independence. PMID- 1521241 TI - Trisomy 4 in a case of acute lymphocytic leukemia (L1). AB - Trisomy 4 has been identified previously as a chromosome abnormality associated with acute nonlymphocytic leukemia (ANLL) with myelomonocytic lineage and in myelodysplastic syndromes (MDS). We report a case of acute lymphocytic leukemia (ALL) (French-American-British, FAB L1) in a 42-year-old Japanese man, with trisomy 4 as the sole chromosomal anomaly. Immunophenotypically, the leukemic blasts demonstrated reactivity with CD2, CD5, and CD7 and indicated on early stage of T cell. PMID- 1521242 TI - The New York Times: "all the news that's fit to print" about medicine and science? PMID- 1521243 TI - Differential expression of DNAseI-sensitive sites in metaphase chromosomes of T and B lymphocytes. AB - Thirty-one recurrent DNAseI-sensitive sites were expressed in G-banded metaphases of cultured T and B lymphocytes. Approximately one-half of these sites were found in both T and B cells and the other half were differentially expressed in the two cell types. The DNAseI-sensitive sites showed a strong correlation with the chromosomal gene location of T-cell receptors, interleukins produced by lymphocytes, and mapped surface antigens involved in the activation/proliferation of lymphocytes. The findings suggest that the chromatin of these very active genes remain accessible to DNAseI during cell division, and may help determine their precise chromosomal location. PMID- 1521244 TI - Trisomy 8 and 11 in refractory anemia with excess blasts in transformation (RAEB T). AB - There are no specific chromosomal abnormalities associated with refractory anemia with excess blasts in transformation [RAEB-T]. An 80-year-old white male with RAEB-T was found to have trisomies of chromosomes 8 and 11, i.e., 48,XY,+8,+11. To our knowledge, this chromosomal abnormality in RAEB-T has not been previously reported. PMID- 1521245 TI - The nurse as a social force: the Christian perspective. Statement of commitment by the NCF of the Philippines. PMID- 1521246 TI - One man goes through a nursing experience. PMID- 1521247 TI - Singleness (a bonus not a burden). PMID- 1521248 TI - Identity. PMID- 1521249 TI - Women in decision-making: advancing the profession. PMID- 1521250 TI - [Congestive heart failure. A systemic or a multiregional syndrome?]. PMID- 1521251 TI - [An echographic study of left ventricular function in acute myocardial infarct undergoing thrombolysis]. AB - To evaluate the changes of left ventricular diastolic and systolic function and the timing of these changes in the early stages of acute myocardial infarction, serial echocardiograms were performed in 10 male patients (mean age of 56 years) with acute myocardial infarction, undergoing reperfusion by thrombolysis (recombinant tissue plasminogen activator). Echocardiograms were performed before reperfusion and 3, 6, 12, 24, 48, 72 hours, 7 and 14 days after thrombolysis. Significant differences of heart rate, systolic and diastolic blood pressure, left ventricular end diastolic volume, end-systolic volume and ejection fraction were not found. The mean regional wall motion index improved from 1.02 +/- 0.50 to 0.89 +/- 0.51 (p less than 0.05) at 48 hours; to 0.79 +/- 0.46 (p less than 0.01) at 72 hours; to 0.69 +/- 0.43 (p less than 0.001) at 7 days and to 0.61 +/- 0.40 at 14 days (p less than 0.001). The deceleration time decreased from 223 +/- 33 to 169 +/- 30 ms (p less than 0.001) 24 hours after reperfusion without further improvement. E peak velocity and E/A ratio significantly increased at 72 hours, while A peak velocity was not statistically different. A slow and progressive recovery of left ventricular function occurred after thrombolysis in acute myocardial infarction. Left ventricular diastole improves earlier while regional systolic function improves slowly till the hospital discharge. PMID- 1521252 TI - [Transcatheter radiofrequency modulation and ablation of the atrioventricular junction in supraventricular arrhythmias refractory to medical therapy]. AB - In patients with supraventricular tachyarrhythmias refractory to medical therapy, transcatheter ablation (TA) is necessary. From January 1990, in 27 patients with nodal tachycardia and 6 with atrial fibrillation or flutter, referred to our institution for electrophysiologic evaluation, TA by radiofrequency (RF) was performed, respectively for atrioventricular (AV) junction modulation and total AV junction ablation. In all these cases, a total refractoriness to several antiarrhythmic drugs alone or in combination had been observed. The RF current, generated by the Osypka HAT 100 device, was administered through a tripolar USCI 7 F catheter. The ideal site for energy delivery was defined on the basis of a mapping, performed in the AV junction area to find out the most premature retrograde atrial activation. Local atrial activation time was evaluated during nodal tachycardia by delivering a premature ventricular extrastimulus to discover the atrial deflection from the ventricular one. In the selected area, 5 applications (range 1-12) of 20-25 W power RF energy for 5-30 s were delivered on average. A complete prevention of nodal tachycardia was achieved in 26/27 patients (96.2%). Only in 2 patients (7.4%) a total AV block was induced. The pre and post-procedure values are as follows: AH = pre 71 +/- 18, post 113.2 +/- 53; HV = pre 46.4 +/- 8, post 48 +/- 7; anterograde Wenckebach point = pre 352 +/- 56, post 389 +/- 91; retrograde Wenckebach point = pre 338 +/- 75, post 419 +/- 61. In 13/27 cases the AH interval was normal after RF application. The retrograde conduction was worsened in all patients and totally abolished in 12/27.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1521253 TI - [Microcirculatory changes in mitral prolapse as an expression of a systemic change in the connective tissue]. AB - Many authors hypothesize that mitral valve prolapse (MVP) can be, in most cases, only a clinical sign of a primitive and systemic disorder of the connective tissue, like in Marfan Syndrome (MS). In our previous works we supported the presence of morphological and functional alterations of the microcirculation in patients affected by MS. In order to characterize a possible common denominator between these pathologies we have studied the cutaneous microcirculation in a group of patients affected by MVP, divided into 2 groups: anatomic MVP (MVP) and MVP syndrome (MVPS). The morphologic parameters have been investigated by nailfold capillaroscopy while digital laser-Doppler was used to study skin flowmetry. The results have been compared with a control group. Capillaroscopic remarkers showed an architecturally disorganized microvasculature with aspects related to a reduced compactness of the microvasculature unit with a significatively higher score compared with controls (7.3 +/- 2.9 vs 3.6 +/- 1 p less than 0.0005). Laser-Doppler flowmetry showed a significatively reduced rest flow; ischemic test showed: spike time 48.9 +/- 36.9 vs 15.3 +/- 7.7 s (p less than 0.0005), hyperemic acme 6.6 +/- 2.7 vs 12.5 +/- 8.4 UP (p less than 0.002); % increase 32.1 +/- 20.2 vs 51.5 +/- 15.4 (p less than 0.002). Thermic test showed a significatively higher thermic acme 8.7 +/- 4.2 vs 12.6 +/- 9.11 UP (p less than 0.05). These results appeared to be correlated with stage pathology as it was observed a severe microvasculature disorders in MVPS. Therefore we suppose that a phenotypic continuum may exist between MS and MVP. PMID- 1521254 TI - Transcatheter ablation of the accessory pathway in 2 patients with life threatening tachyarrhythmias. AB - Successful transcatheter ablation of an accessory pathway in 2 patients with life threatening tachyarrhythmias is reported. In both cases, electrophysiological evaluation documented the posterior septal location of the anomalous atrioventricular connection. Radiofrequency current energy was delivered just below the coronary sinus orifice, and resulted in disappearance of preexcitation. During the follow-up, both patients remained free from tachyarrhythmias on no medication, and serial electrocardiographic recordings confirmed the persistent absence of preexcitation. It is concluded that ablation of accessory pathways can be accomplished easily and without risk by means of the radiofrequency catheter technique. This therapeutic modality requires a short hospitalization and can be recommended as the first option in patients with the Wolff-Parkinson-White syndrome. PMID- 1521255 TI - [Accidental ventricular fibrillation during transesophageal atrial overdrive]. AB - Transesophageal atrial overdrive stimulation is a widely used technique for the interruption of atrial flutter and supraventricular tachyarrhythmias. We describe a case of 60 year old man with a previous myocardial infarction, suffering from angina during effort after aortocoronary bypass who presented several episodes of atrial flutter treated with success by transesophageal atrial overdrive stimulation using swallowing electrodes. During the treatment of the last episode of atrial flutter, after a 5 s burst at 300 b/min ventricular fibrillation occurred and was promptly interrupted by DC shock. This is the first case in our experience and probably the first report of ventricular fibrillation induced by swallowing electrodes. Possible mechanisms as pharmacological interactions, accidental ventricular stimulation, etc, are discussed. In conclusion, even though the risk of dangerous arrhythmias is very low, transesophageal atrial overdrive stimulation should be performed by experts in an equipped room. PMID- 1521256 TI - [The myogenic mechanism in the autoregulation of the coronary vascular bed]. PMID- 1521257 TI - Necrotizing sialometaplasia: a review and two case reports. PMID- 1521258 TI - Reduction of the fragmental layer to achieve a more durable porcelain repair. PMID- 1521259 TI - The combination implant crown: a cement- and screw-retained restoration. PMID- 1521260 TI - Endodontic clinical diagnosis: Part 1. PMID- 1521262 TI - Probing the complex issues of AIDS. An ethical argument for voluntary AIDS testing. PMID- 1521261 TI - Analysis of a new barrier infection control system for dental radiographic film. PMID- 1521263 TI - Review of considerations in the management of altered consciousness of a mitral valve prolapse patient. PMID- 1521264 TI - Endodontic clinical diagnosis: Part 2. PMID- 1521265 TI - Senate Bill 1670. PMID- 1521266 TI - HIV disease: pathogenesis and disease progression--an update. PMID- 1521267 TI - The cingulo-radicular groove: its significance and management--two case report. PMID- 1521268 TI - Guided tissue regeneration: biologic rationale, surgical technique, and clinical results. PMID- 1521269 TI - Guided tissue regeneration: clinical applications associated with dental implants. PMID- 1521270 TI - Guided tissue regeneration using Vicryl periodontal mesh. PMID- 1521271 TI - The use of collagen membranes for guided tissue regeneration. PMID- 1521273 TI - Is dentistry ready for a prolonged recession? PMID- 1521272 TI - Calcium sulfate: a biodegradable and biocompatible barrier for guided tissue regeneration. PMID- 1521274 TI - Ceramic or ceramist? Category 1--the all-ceramic restoration. PMID- 1521275 TI - Guidelines for clinical management of temporomandibular disorders: Part 1. PMID- 1521276 TI - The use of guided tissue regeneration in enhancing anterior esthetics: a case report. PMID- 1521277 TI - Diabetes mellitus and xerostomia. PMID- 1521279 TI - The legend of the toothworm. PMID- 1521278 TI - An interdisciplinary approach to the management of the adult mutilated dentition: a case report. PMID- 1521280 TI - Probing the complex issue of AIDS. PMID- 1521281 TI - Consideration of linear and angular values of maximum mandibular opening. PMID- 1521282 TI - Viability, transmissibility, and risk assessment of HIV. PMID- 1521283 TI - Prosthetic reconstruction of the wear case: a case report. PMID- 1521284 TI - Guidelines for clinical management of temporomandibular disorders: Part 2. PMID- 1521285 TI - Treatment of snoring and obstructive sleep apnea. PMID- 1521286 TI - Female dentists: vive la difference! PMID- 1521287 TI - Common oral findings in two different diseases--leukemia and AIDS: Part 1. PMID- 1521288 TI - Evaluation of root instruments. PMID- 1521289 TI - The clinical pharmacology of Ketorolac. PMID- 1521290 TI - The role of smoking in the progression of periodontal disease: a literature review. PMID- 1521291 TI - One-step impression technique for patients with severe undercuts. PMID- 1521292 TI - Changing number of dental specialists. PMID- 1521293 TI - Clinical use of Beta-Quartz Glass-Ceramic Inserts. PMID- 1521294 TI - Adjunct use of dexamethasone in postoperative dental pain control. PMID- 1521295 TI - The infected toothbrush, the infected denture, and transmission of disease: a review. PMID- 1521296 TI - Chronic mucositis: differential diagnosis and therapeutic management. PMID- 1521297 TI - Who is paying for dental care? PMID- 1521298 TI - Endodontic surgery in posterior teeth--its role in maintaining arch integrity. PMID- 1521299 TI - Innovative uses of ultrasonic energy for the elimination of problematic root canal obstructions. PMID- 1521300 TI - Ear pain: a dental dilemma. PMID- 1521301 TI - A preview of the canal-filling materials of the 21st century. PMID- 1521302 TI - Why finding dental auxiliaries has not been easy. PMID- 1521303 TI - Effects of chewing gums sweetened with sorbitol or a sorbitol/xylitol mixture on the remineralisation of human enamel lesions in situ. AB - Intra-oral remineralisation of experimental caries-like lesions in human enamel, as determined by polarised light microscopy and quantitative microradiography, was promoted to a similar extent (% fall in delta Z, 18.6 and 19.0) by chewing a sorbitol or sorbitol/xylitol (3:1)-sweetened gum for 20 min after each of three meals and two sugary snacks daily. The results suggest that reported differences in the properties of the two sweeteners do not affect their ability to enhance remineralisation due to salivary stimulation. PMID- 1521304 TI - Purification, characterization and inhibition by fluoride of enolase from Streptococcus mutans DSM 320523. AB - Enolase from Streptococcus mutans has been purified to homogeneity by a three step procedure. As shown by analytical ultracentrifugation and polyacrylamide gel electrophoresis under denaturing conditions, the purified enzyme is an octamer with molecular weight Mr = 360 kDa, composed of eight identical subunits with Mr = 45 kDa. The kinetic parameters of S. mutans enolase in the presence of 1 mM Mg2+ are Aspec = 130 IU x mg-1 and KM = 0.44 mM as determined by steady-state experiments in the D-glycerate 2-phosphate to enolpyruvate phosphate reaction. Enzymatic activity is inhibited noncompetitively by fluoride in the range between 0 and 10 mM NaF yielding Ki = Kii = 1.39 mM, but inhibition characteristics become competitive when tested above 10 mM. In the presence of only small amounts of phosphate (0.5 mM) the inhibitory effect of fluoride is enhanced dramatically yielding Ki = 0.26 mM. Inhibition by NaPO3F is competitive with Ki = 0.9 mM, indicating that free fluoride ions in combination with phosphate are more effective in inhibiting S. mutans enolase. It can be concluded that inhibition of enolase by fluoride in combination with phosphate can influence glycolysis in S. mutans and so reduce acid production or even growth rate, thereby leading to potential anticariogenic effects. PMID- 1521305 TI - Effects of tung oil on salivary viscosity and extent and incidence of dental caries in rats. AB - Increased salivary viscosity may be associated with an increase in dental caries. In order to examine this relationship, the caries level in rats was monitored following gastric intubation with tung oil which has been shown to significantly increase salivary viscosity. Tung oil intubation over an 8-week period significantly increased the salivary viscosity in rats as compared with deoinized water and corn oil intubation. The total number of carious lesions was significantly increased (p less than 0.05) in the tung oil intubated rats as compared with the two other groups. This increase in carious lesions was primarily associated with the smooth surfaces of the teeth. There was also a significant increase (p less than 0.05) in the extent of enamel and dentin involvement of the tung oil intubated rats as compared with the other two groups. Histologic examination of the submandibular glands revealed an increase in the amount of glycoprotein material in the convoluted granular tubules of the tung oil intubated rats as compared with the deionized water and corn oil intubated animals. Collectively, these results suggest that tung oil intubation is correlated with both increased salivary viscosity and increased smooth-surface dental caries, suggesting that the viscosity may be related to dental caries progression. PMID- 1521306 TI - Effects of hyposalivation on the oral microflora of rats fed sucrose or wheat flour diets. AB - The effects of hyposalivation on the induction of dental caries and on the composition of the oral microflora were examined in specific pathogen-free Sprague-Dawley rats fed either a sucrose or a wheat flour diet with or without inoculation of Streptococcus mutans. Significant dental caries was induced in hyposalivated rats fed diet 2000 containing 56% sucrose, irrespective of infection by S. mutans. Diets containing 56% wheat flour did not induce dental caries in either hyposalivated or sham-operated rats, irrespective of infection by S. mutans. Bacteriological examinations at the end of the experiment demonstrated that the total numbers of lactobacilli and staphylococci increased in hyposalivated rats irrespective of the diet given, while the inoculated stain of S. mutans decreased significantly in hyposalivated rats. These findings suggest that some acidogenic microorganisms such as lactobacilli and staphylococci that can utilize sucrose or glucose but not wheat flour may also promote dental caries in hyposalivated rats. PMID- 1521307 TI - Effects of arginine and arginyl-L-arginine on the glucose-mediated pH fall of Streptococcus rattus and Streptococcus milleri (short communication). PMID- 1521308 TI - An in vivo comparison of radiographic and directly assessed clinical caries status of posterior approximal surfaces in primary and permanent teeth. AB - At general dental practices in Scotland 211 children between the ages of 5 and 15 years were examined by 1 observer. A comparison of the status of 1,468 permanent and 756 primary posterior approximal surfaces was made on the basis of their appearance on posterior bite-wing radiographs and the findings of a direct in vivo visual examination, made after temporary tooth separation had been achieved over 1 week using elastomeric separation. For permanent tooth surfaces, 0% of radiolucencies in the outer half of enamel, 10.5% in the inner half of enamel, 40.9% extending to the outer half of dentine, and 100% extending to the inner half of the dentine were found clinically to be cavitated. The analogous results for primary teeth were that 2.0, 2.9, 28.3, and 95.5%, respectively, of radiolucencies appeared to be cavitated. Although further research with larger numbers of permanent teeth is indicated, these results may contribute to a re evaluation of the optimal threshold for restorative intervention at approximal sites. Greater numbers of approximal radiolucencies and carious lesions (p less than 0.001) were found in those surfaces which initially had a normal anatomical contact when compared to those which did not. PMID- 1521309 TI - Hexahedrally based crystals in human tooth enamel. AB - Mg-containing calcium phosphate crystals including pseudocuboidal, rhombohedral shapes and groupings of quadrangular blades cubically arranged were found in human tooth enamel by scanning electron microscopy and by electron probe microanalysis. In caries-free old enamel, these hexahedrally based crystals measuring 0.5-2.5 microns in length were observed in some crevices of tufts and lamellae. The crystals were rarely seen in the inner crevices of caries-free exfoliated deciduous enamel and none could be seen in sound young enamel. In brown-coloured old enamel possessing arrested caries with lamellae, some of the lamellae contained crystals measuring 0.1-1.5 mu in length adjacent to half dissolved prisms. These crystals, identified as Mg-containing whitlockite, will grow during a long period after eruption of the tooth or during the enamel caries process. PMID- 1521310 TI - The influence of various amphiphilic phosphates on in vitro caries lesion formation in human dental enamel. AB - Some newly designed surface-active phosphates were investigated with respect to their capacity to inhibit caries lesion formation in vitro. On the labial or buccal surfaces of sound human third molars, windows were prepared for investigation. One half of each window was treated with the test compound at pH values of 7.5, 5.5, or 3.5. The other half served as a control. Both halves were demineralized and the generated caries lesions in both parts were compared by means of quantitative microradiography. Mono-, bis- and trisphosphates differed only marginally in their effect on the demineralization. The compounds diminished the demineralization down to 30% of that of untreated enamel. Per molecule at least one long alkyl chain (more than 12 C atoms) was required for achieving decreased demineralization, indicating the importance of a low surface tension. The results suggest that some of the tested compounds have promising properties for their use as anticaries agents, especially when applied in combination with fluoride. PMID- 1521311 TI - An in vitro assessment of the extent of caries under small occlusal cavities. AB - Many clinicians take for granted that occlusal caries which is just visible as a cavity is extended (deep) into the dentine. This study was aimed at quantifying this opinion. The study was carried out with 60 molars containing small but visible occlusal cavities. After taking bite-wing radiographs the crowns were separated from the roots and embedded. 700-microns sections were cut and glued on plastic sheets. X-ray pictures were taken of the sections which were scored by independent examiners. The bite-wings provided inaccurate estimates of the extent of caries. Radiographs of the sections revealed that about 25% of the molars had caries which reached just to the dentino-enamel junction, while the remaining 75% showed caries extending far into the dentine. PMID- 1521312 TI - Determination of volumes of fluid in the mouth by fluoride dilution. AB - A dilution technique, with fluoride as a marker, has been developed to measure the volume of saliva and other fluids in the mouth. Immediately after swallowing, a small amount of fluoride solution is placed in the mouth, mixed with the oral fluids, and expelled from the mouth. The fluoride concentration of the expelled oral fluid is measured and the volume of fluid in the mouth at the time of spitting calculated from the fluoride dilution. Mean values of 0.75 +/- (SD) 0.28 ml for males and 0.72 +/- (SD) 0.16 ml for females were recorded. The accuracy of the volume determination is about +/- 0.10 ml in vivo. This technique has provided a convenient and rapid means of determining saliva volumes. It could also be used to determine rates of secretion and may prove useful in the clinic for assessing a patient's salivary competence. PMID- 1521313 TI - Limitations in the intraoral demineralization of bovine enamel. AB - A model system was used to examine the relation between the duration of plaque pH fall and enamel demineralization following the intake of dietary carbohydrate in humans. Subjects wore palatal appliances containing blocks of bovine enamel covered with Streptococcus mutans IB 1600, and rinsed with 5 or 10% sucrose. Changes in iodide penetrability (delta Ip) of the enamel, and the pH and extracellular calcium and inorganic phosphate (Pi) concentrations of the streptococcal plaque were determined. Following rinses with 5% sucrose, delta Ip increased with time and reached a maximum (11.2 +/- 2.2 units) at 45-60 min although the S. mutans plaque remained acidic (pH = 4.8 +/- 0.6). After 10% sucrose, the maximum (14.7 +/- 3.1 units) was reached while the plaque pH was 4.0 +/- 0.3. Second rinses with sucrose increased delta Ip at most by 30%. Thus, demineralization did not persist throughout the period of low plaque pH, but occurred primarily during the early phase of plaque acidogenesis. Enamel demineralization appeared to be limited by factors other than the pH of the streptococcal plaque. Calcium concentrations in the S. mutans plaque rose to a maximum of 10.9 +/- 2.8 mEq/l at 30 min after the 5% sucrose rinses, then fell; Pi reached a stable level of 12.2 +/- 2.3 mEq/l by 60 min. Calculations showed that conditions approached saturation with respect to enamel and dicalcium phosphate dihydrate as demineralization reached a maximum. Demineralization appeared to be limited at low plaque pH, therefore, by the accumulation of high levels of mineral ions in the streptococcal plaque.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1521314 TI - Reliability of Doppler echocardiographic stroke volume measurement. AB - To evaluate the accuracy and utility of the echocardiographic Doppler method of determining the stroke volume, the stroke volume was measured in 64 instances in 15 patients and compared to the simultaneous thermodilution stroke volume determinations. Stroke volume, varied by atrial pacing at various heart rates, was calculated noninvasively by the product of the cross-sectional area of the aortic orifice determined by echocardiography and the flow velocity integral measured by continuous wave Doppler. While the cardiac output was increased moderately by atrial pacing, the stroke volume was decreased in relation to the increase in the heart rate. The stroke volume calculated by the echo-Doppler method exhibited a significant linear relationship to the stroke volume determined by thermodilution (r = 0.84) and to the cardiac output (r = 0.75, p less than 0.01). Inter-observer and intra-observer variability was 7 +/- 4% and 5 +/- 4%, respectively. The noninvasive echo-Doppler method of estimating the stroke volume is concluded to be accurate, specifically, to be comparable to the values obtained by thermodilution and with a low inter- and intra-observer variability. PMID- 1521315 TI - Alterations in nuclear envelope invaginations in axotomized fetal and early postnatal hamster facial motoneurons. AB - In this study, changes in the amount of nuclear envelope invaginations (NEI) were morphometrically assessed after axotomy during late fetal and early postnatal developmental stages in hamster facial motoneurons. These changes were expressed as boundary density or BA (length of nuclear envelope per unit area of nucleus). Axotomy-induced changes in nuclear area and perimeter were also quantitatively determined. At 17 h after axotomy in the fetal operative series, no changes in any of the parameters were seen. At 1 day postoperative (dpo) in newborn, 2 and 4 postnatal day animals, the boundary densities of the total and invaginated portion of the nuclear envelope increased significantly. No corresponding qualitative changes were observed. At 2 dpo in 4 and 7 postnatal day animals, there were significant increases in the boundary densities of both invaginated and total nuclear envelope and a decrease in nuclear area. These changes were not seen at 2 dpo in the 9-day operative series. At 4 dpo in 7 and 9 postnatal day animals, scalloping of the normally smooth nuclear profile, as well as a flattening and elongation in nuclear shape, occurred. These qualitative changes in the 7 and 9 day operated groups were also accompanied by significant changes in all the measured parameters. The boundary density of the invaginated, non invaginated and total nuclear envelope increased; whereas, nuclear area and perimeter decreased. These results argue against the generally held hypothesis that an increase in nuclear envelope invaginations is indicative of an allied increase in cellular metabolism.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1521316 TI - Expression of lectin binding in the superficial dorsal horn of the rat spinal cord during pre- and postnatal development. AB - The plant lectin Bandeiraea simplicifolia I-B4 binds to the soma and central terminals of a subpopulation of unmyelinated primary sensory neurones in the adult rat. The binding site of this lectin is thought to be the terminal alpha-D galactose residue of a membrane associated glycoconjugate which may be involved in the development of specific connections between small diameter primary sensory neurones and second order neurones in the superficial dorsal horn of the spinal cord. To begin to investigate this possibility we have examined the development of lectin binding in the dorsal horn of pre- and postnatal rats. Lectin binding first appeared on axon profiles in the superficial dorsal horn of the spinal cord at embryonic days 18/19. Previous studies in the rat have revealed that the central processes of small diameter primary sensory neurones enter the dorsal horn at embryonic days 18/19. Our findings suggest that the glycoconjugate to which this lectin binds, is expressed by the central processes of small diameter primary sensory neurones as they grow into the spinal cord. It is therefore possible that this glycoconjugate is involved in the development of topographically ordered neural connections within the dorsal horn of the spinal cord. PMID- 1521317 TI - Differential distribution of two microtubule-associated proteins, MAP2 and MAP5, during chick dorsal root ganglion development in situ and in culture. AB - Microtubule-associated proteins (MAPs) are essential components necessary for the early growth process of axons and dendrites, and for the structural organization within cells. Both MAP2 and MAP5 are involved in these events, MAP2 occupying a role predominantly in dendrites, and MAP5 being involved in both axonal and dendritic growth. In the chick dorsal root ganglia, pseudo-unipolar sensory neurons have a T-shaped axon and are devoid of any dendrites. Therefore, they offer an ideal model to study the differential expression of MAPs during DRG development, specifically during axonal growth. In this study we have analyzed the expression and localization of MAP2 and MAP5 isoforms during chick dorsal root ganglia development in vivo, and in cell culture. In DRG, both MAPs appeared as early as E5. MAP2 consists of the 3 isoforms MAP2a, b and c. On blots, no MAP2a could be found at any stage. MAP2b increased between E6 and E10 and thereafter diminished slowly in concentration, while MAP2c was found between stages E6 and E10 in DRG. By immunocytochemistry, MAP2 isoforms were mainly located in the neuronal perikarya and in the proximal portion of axons, but could not be localized to distal axonal segments, nor in sciatic nerve at any developmental stage. On blots, MAP5 was present in two isoforms, MAP5a and MAP5b. The concentration of MAP5a was highest at E6 and then decreased to a low level at E18. In contrast, MAP5b increased between E6 and E10, and rapidly decreased after E14. Only MAP5a was present in sciatic nerve up to E14. Immunocytochemistry revealed that MAP5 was localized mainly in axons, although neuronal perikarya exhibited a faint immunostaining. Strong staining of axons was observed between E10 and E14, at a time coincidental to a period of intense axonal outgrowth. After E14 immunolabeling of MAP5 decreased abruptly. In DRG culture, MAP2 was found exclusively in the neuronal perikarya and the most proximal neurite segment. In contrast, MAP5 was detected in the neuronal cell bodies and all along their neurites. In conclusion, MAP2 seems involved in the early establishment of the cytoarchitecture of cell bodies and the proximal axon segment of somatosensory neurons, while MAP5 is clearly related to axonal growth. PMID- 1521318 TI - Effects of prenatal morphine on adult sexual behavior and brain catecholamines in rats. AB - Female rats exposed to morphine in utero (5-10 mg/kg twice a day on days 11-18 of gestation) were significantly inhibited in their sexual behavior when compared to saline-exposed controls. In contrast, males exposed prenatally to morphine had shorter post-ejaculatory intromission latencies and, after the first test, exhibited increased mounting and intromitting activity relative to controls. Examination of the brain catecholamine content revealed that morphine in utero may permanently alter adult hypothalamic norepinephrine levels in male and female rats. The morphine-induced alterations in hypothalamic norepinephrine levels were sexually dimorphic. In the hypothalamus of male rats, norepinephrine content was increased 95%, whereas in the hypothalamus of female rats it was decreased 57% relative to controls. These results suggest that prenatal morphine exposure, which differentially affects adult male and female sexual behavior, also alters hypothalamic norepinephrine content in a sexually dimorphic fashion. PMID- 1521319 TI - Postnatal administration of dihydrotestosterone to the male rat abolishes sexual dimorphism in the accessory olfactory bulb: a volumetric study. AB - The regulatory action of the non-aromatizable androgen dihydrotestosterone (DHT) on sexual differentiation of the volume of the rat accessory olfactory bulb (AOB) was studied. Postnatal treatment with DHT (180 micrograms/day) carried out daily between days 6 and 20 produced a drastic reduction in overall AOB size and that of its constituent neural layers in genetic males with respect to intact and control males. The volumetric measures found in DHT-treated males did not differ from those shown by the intact females. These results, which indicate a demasculinization and a feminization of the AOB volume in gonadally intact male rats induced by DHT, are discussed in relation to the presumably regulatory role of DHT on neuron populations during the sexual organizational process of the brain. PMID- 1521320 TI - Developmental changes in brain kynurenic acid concentrations. AB - The cerebral distribution and regulation of excitatory amino acid levels may play a crucial role in neuronal development. In the present study we examined concentrations of the endogenous excitatory amino acid antagonist kynurenic acid and related substances during development in fetal and neonatal rat brain and fetal non-human primate cerebral cortex. Kynurenic acid concentrations in rat fetal whole brain were significantly increased 4-5 fold prenatally, then declined rapidly at 1 day after birth, and reached adult concentrations at 7 days after birth. L-Kynurenine concentrations were also markedly increased prior to birth and then declined to adult concentrations at 1 day after birth. L-Tryptophan was increased 3 fold before birth, and decreased to adult concentrations 1 day after birth. In contrast concentrations of dopamine, norepinephrine, 3,4 dihydroxyphenylacetic acid and homovanillic acid increased 1 day prior to birth and continued to increase following birth. Fetal baboon cerebral cortex showed significant increases in kynurenic acid concentrations both pre-term and near term as compared with adult concentrations. These results show that marked changes in kynurenic acid concentrations occur prior to and following birth. It is possible that high levels of kynurenic acid prior to birth inhibit neurite branching and development of excitatory synapses, which then develop rapidly in parallel with the decrease in kynurenic acid levels. PMID- 1521321 TI - Kindling in developing animals: interactions between ipsilateral foci. AB - In adult rats, concurrent kindling of two limbic sites, alternating stimulation to each site, often results in the retarding of kindling at one or both sites. This inhibitory interaction between two limbic kindling foci is termed kindling antagonism and occurs irrespective of whether the sites are contralateral or ipsilateral. We have previously shown that kindling antagonism does not occur when 16- to 17-day-old rat pups are concurrently kindled in the hippocampus and contralateral amygdala or between the two amygdalae. In this study, adult and 16- to 17-day-old rats were concurrently kindled in the hippocampus and ipsilateral amygdala to determine if the local intrahemispheric mechanisms suppressing multiple kindled foci are age-dependent. Kindling antagonism occurred in 7 out of 10 adult rats. In contrast, in rat pups, kindling development was not suppressed. Concurrent kindling of the two limbic sites enhanced the development of severe seizures. Two 16- to 17-day-old rats receiving alternating stimulations exhibited spontaneous seizures. The age-specific failure of both inter- and intrahemispheric mechanisms to suppress the development of multiple kindling foci may explain the high incidence of multifocal seizures in the immature CNS. PMID- 1521322 TI - Laminin--developmental expression and role in axonal outgrowth in the peripheral nervous system of the chick. AB - The possible role of laminin on axon outgrowth and guidance in vivo was examined by: (1) determining its developmental expression, and relationship to outgrowth of sensory, motor and sympathetic axons in the chick embryo; and (2) evaluating the changes in the pattern of sympathetic preganglionic projections subsequent to injections of laminin, antilaminin and other laminin function blockers (JG22, INO) into their pathways during axon outgrowth. Double immunofluorescent staining for laminin and neurofilaments in peripheral nerves prior to and during initial outgrowth showed no obvious relationship between laminin and potential nerve pathways. Even though weak laminin immunostaining is apparent throughout the mesenchyme through which axons grow, the most prominent laminin immunostaining is on basement membranes of the neural tube, notochord and dermamyotome. However, as peripheral nerves mature, laminin becomes localized to nerve fascicles throughout the peripheral nervous system, beginning with the dorsal and ventral roots, and progressing later to more distal spinal nerves. Microinjections of antilaminin, JG22 (a monoclonal antibody against laminin/fibronectin receptors) and INO (a monoclonal antibody against a laminin-heparan sulfate proteoglycan complex) into the pathway of sympathetic preganglionic axons prior to and during outgrowth had no effect on the spatio-temporal patterns of sympathetic preganglionic projections. An alternate laminin-rich pathway produced by injecting laminin into the region of the sympathetic trunk immediately adjacent but caudal to the T1 spinal level also did not alter the projection of T1 preganglionic axons. These results suggest that laminin may not be crucial to the initial of peripheral axons. The localization of laminin in nerve fascicles in later stages of development suggests instead that laminin may be important in the maintenance of these structures. PMID- 1521323 TI - Behavioral effects of continuous hippocampal stimulation in the developing rat. AB - There is controversy as to whether prolonged seizures are more detrimental to the immature than the mature brain. To evaluate this question continuous hippocampal stimulation was used to induce prolonged limbic seizures in 20-, 30- and 60-day old rats. The long-term effects on learning and activity level were then studied at age 80 days using the Morris water maze, a test of spatial learning and memory, and the open field test, a test of an animal's reaction to a novel environment. Limbic status epilepticus in 60-day-old but not 20- and 30-day-old rats caused long-term impairment of learning in the Morris water maze. No differences were noted between the control and the experimental animals in the open field test. These results suggest that the age of seizure onset is an important determinant of long-term cognitive sequelae. PMID- 1521324 TI - Platelet-derived growth factor B-chain-like immunoreactivity in the developing and adult rat brain. AB - Platelet-derived growth factors (PDGFs) are growth-regulatory molecules that stimulate chemotaxis, proliferation and increased metabolism, primarily of connective tissue cells. In our previous paper, we have demonstrated the ubiquitous localization of PDGF B-chain-containing proteins in neurons and expression of transcripts for PDGF A-chain, B-chain and the two forms of the PDGF receptor in the brains of non-human primates. In the present study, the cellular localization of PDGF B-chain in developing and adult rat brains was analyzed using immunocytochemistry with a PDGF B-chain-specific monoclonal antibody. Intense PDGF B-chain immunoreactivity (PDGFB-I) was distributed around the continuously regenerating primary olfactory neurons at all stages of development from embryo to adult. The major part of PDGFB-I associated with neurons appeared some time after birth and increased with age. PDGFB-I appeared in several nerve fiber systems during earlier stages of development and gradually decreased with age. In conjunction with other data showing the existence of functional PDGF receptor beta-subunits in the neurons, these data suggest a possible role for PDGF B-chain as a neurotrophic or neuroregulatory factor in both developing and mature brains. PMID- 1521325 TI - The mas proto-oncogene is developmentally regulated in the rat central nervous system. AB - The mas proto-oncogene encodes a protein with a predicted structure similar to members of the family of seven transmembrane domain spanning receptors. These receptors are thought to transduce extracellular signals to G-proteins. Angiotensin II and III have been reported to be the functional ligands for the mas oncogene-encoded receptor (Jackson et al., 1988). We show here using in situ hybridization histochemistry and RNase protection assays that mas mRNA is expressed in a subpopulation of neurons in both the adult and developing rat CNS. In the adult CNS, mas mRNA is most abundant in hippocampal pyramidal neurons and dentate granule cells; mas transcripts are also present at low levels in the cortex and thalamus. mas is first expressed in the developing rat CNS at postnatal day 1 (P1). Even at this early stage in CNS development the pattern of mas expression is similar to that seen in the adult. Although at P1 most neurons of the dentate gyrus are not yet generated and cells of the hippocampal CA fields are undergoing migration and synaptogenesis (Bayer 1980; Altman and Bayer, 1990a, 1990b, 1990c), mas is specifically expressed in these cell populations. This extremely restricted pattern of expression suggests that mas may function in determining the morphology and connections of specific cell types in the hippocampus. This function may in part be carried out by the ability of mas to link external cues to intracellular processes. PMID- 1521326 TI - Transient c-fos expression accompanies naturally occurring cell death in the developing interhemispheric cortex of the rat. AB - We have searched for the possible correlation of naturally occurring cell death with spontaneously enhanced c-fos expression in the developing cerebral cortex of normal Wistar albino rats. During the late prenatal and early postnatal period, cells with irregular contours and intracytoplasmic electron-dense granules (granule-containing cells) were apparent in the interhemispheric cortex, including the anterior cingulate and the retrosplenial cortices. These cells were loosely packed within the cortical layers derived from the cortical plate. Having excluded the possibility that these cells could be phagocytes by immunocytochemical experiments, we propose that they are cells in different phases of a process of autophagic degeneration and death. Images of extreme nuclear pyknosis were also apparent in identical locations. Cells showing immunoreactivity for c-Fos protein appeared in the same cortical areas. The immunoreactive cells were very abundant in the retrosplenial cortex, but were also present in the anterior cingulate cortex. These cells showed markedly irregular contours and large, densely immunoreactive intracytoplasmic inclusions; these images were similar to those of granule-containing cells revealed by conventional stains. The immunoreactivity for c-Fos protein was ephemeral, occurring exclusively during embryonic days 20 and 21, but granule-containing cells were observed for a longer period. The present results provide evidence, albeit indirect, that c-fos expression may occur in certain neural cells at the onset of a process of death by autophagia, and suggest a possible involvement of the proto-oncogene c-fos in certain forms of naturally occurring neuronal death. PMID- 1521327 TI - Neurogenesis of the amygdaloid nuclear complex in the rhesus monkey. AB - The time course of neurogenesis for neurons which comprise the amygdaloid complex in Rhesus monkeys was determined using tritiated thymidine autoradiography. Fourteen pregnant monkeys received injections of tritiated thymidine between embryonic days 27 (E27) and 56 of their 165 day gestation and offspring were sacrificed during the early postnatal period. The first neurons destined for the amygdaloid complex were generated at E33 making them among the earliest postmitotic neurons in the telencephalon. Neurogenesis peaked within all nuclei of the amygdaloid complex between E38 and E48 and had ceased between E50 and E56. While amygdaloid neurogenesis in postnatally sacrificed monkeys displayed a dorsal-to-ventral gradient of radiolabeled neurons, the considerable rotation of the temporal lobe during the latter stages of primate development indicates that neurogenesis in the embryo, during the first third of gestation, actually occurs across a medial-to-lateral gradient. This medial-to-lateral gradient occurs as a smooth wave across the amygdaloid nuclei and does not respect neuroanatomical subdivisions or patterns of connectivity of the amygdaloid nuclei in the Rhesus monkey. PMID- 1521328 TI - Hydra head activator peptide has trophic activity for eukaryotic neurons. AB - The synthetic undecameric peptide, pGlu-Pro-Pro-Gly-Gly-Ser-Lys-Val-Ile-Leu-Phe, known as the hydra head activator peptide, present in high concentrations in mammalian hypothalamus and intestine, was tested for neurotrophic activity in a survival assay using cultured chick embryonic sympathetic and dorsal root ganglion cells, and for morphological differentiation activity on neuroblastoma cells. Hydra head activator peptide supported neuron survival. The optimal active concentration, 1 pM, was very similar to the concentration that causes bud and head formation in hydra. Maximal neuron survival obtained with hydra head activator peptide was close to that obtained with nerve growth factor: both substances enhanced survival up to 3 times that of control cultures. Bradykinin, which has some amino acid sequence homology with hydra head activator, was inactive as a neurotrophic factor. Hydra head activator induced rapid morphological differentiation of the mouse neuroblastoma cell line Neuro-2A. Neuro-2A responded to the peptide by process extension, 4 h after its addition to the culture medium. Neurotrophic factors isolated to date have been characterized by their ability to maintain cell viability and enhance neurite outgrowth. Hydra head activator peptide met these two criteria when tested in 3 different neuron culture systems. Our results suggest that the head activator peptide may act as a neurotrophic factor for neurons in other species, including mammals. PMID- 1521329 TI - Generation of analytic plasma lipoprotein profiles using two prepacked superose 6B columns. AB - A simple, low-priced chromatographic system to generate plasma lipoprotein profiles from total human plasma was tested with plasma from normolipidemic subjects and patients with heterozygous familial hypercholesterolemia, hyper alpha-lipoproteinemia, lipoprotein lipase deficiency, familial dysbetalipoproteinemia and familial lecithin-cholesterol-acyl-transferase deficiency. The system appears to be a good alternative to more expensive high pressure liquid chromatography systems, notably in lipoprotein laboratories already provided with equipment for column chromatography. If a microplate photometer and a computer is available in the laboratory, the measurement of various lipids in 70-80 eluant fractions from the columns can be simplified. PMID- 1521330 TI - Homocarnosinosis patients and great apes have a serum protein that cross-reacts with human serum carnosinase. AB - A specific polyclonal antiserum to human serum carnosinase was raised in rabbits and was used to prepare an agarose-protein A-antibody matrix. An antigen capture procedure showed that sera from homocarnosinosis patients, which lack carnosinase activity, contain an immunoreactive protein (M(r) 75,000) indistinguishable from the carnosinase band from normal serum. Other higher primates have active serum carnosinase and a similar immunoreactive M(r) 75,000 protein. The immunoaffinity matrix was used in a facile procedure to isolate pure carnosinase from human plasma with a yield of 69%. The antiserum inhibited human serum carnosinase strongly, but the maximum inhibition attained averaged only 71%. The antiserum inhibited human and chimpanzee serum carnosinases more effectively than gorilla or other higher primate serum carnosinases. PMID- 1521331 TI - High-performance liquid chromatographic determination of free polyamines in human seminal plasma. AB - Putrescine, spermidine and spermine were determined quantitatively in 192 ultrafiltered samples of human seminal plasma with a precision of +/- 1.9% by pre column derivatization with benzoyl chloride and reversed-phase chromatography. The concentrations of free putrescine, spermidine and spermine ranged from 0 to 1.96 mmol/l (mean = 0.10), 0.017-0.96 mmol/l (mean = 0.16) and 0.13 to 20.80 mmol/l (mean = 2.43), respectively. A significant correlation between the amounts of spermidine and spermine was found (r2 = 0.806, P less than 0.0005). Otherwise, no significant correlations between free-polyamine levels and routine spermiogram parameters such as volume, sperm count, motility, vitality and morphology were obtained. PMID- 1521332 TI - Mechanized assay of serum cholinesterase by specific colorimetric detection of released acid. AB - An automated assay method has been developed for the measurement of serum cholinesterase activity. The samples were prepared by an automated liquid handling unit and incubated for 9.7 min at 30 degrees C, followed by automatic injection into a colorimetric flow injection determination system for acetic acid liberated from acetylcholine by cholinesterase catalytic activity. The coloration reaction employed is based upon the formation of 2-nitrophenylhydrazide utilizing a water-soluble carbodiimide and has a high selectivity for carboxylic acids. The coefficients of variation of the proposed method were 2.4% for within-run analysis (n = 14) and 2.6% for between-run analysis (n = 6). Sera of 55 hospitalized patients were analyzed and the values obtained correlated well with an automated differential pH method (gamma = 0.989). PMID- 1521333 TI - Separation of plasma lipoproteins with a tabletop ultracentrifuge. PMID- 1521334 TI - More on monoamine oxidase activity in whole blood. PMID- 1521335 TI - Solving one of the problems of in vitro cytokine production and endotoxin measurement in blood. PMID- 1521336 TI - Intestinal permeability: update on the enzymatic assay of mannitol. PMID- 1521337 TI - The precipitation of histone-proteins with trichloroacetic acid. PMID- 1521338 TI - Discriminant analysis of urinary calculi by near-infrared reflectance spectroscopy. AB - Near-infrared reflectance analysis has been used to determine the qualitative and semi-quantitative composition of urinary calculi. This simple method requires calibration of the most common urinary calculi. Analysis time is short (less than 1 min) and only very small amounts of calculus in powder form (less than 100 micrograms) are required without the use of any reagent. Moreover, when compared to infrared spectroscopy, this method provides sufficient accuracy to identify mixed calculi containing two or three components, and permits semi-quantitative determinations. The speed and simplicity of this technique makes it a powerful method for the routine analysis of urinary calculi in clinical laboratories. PMID- 1521339 TI - Tubular secretion of Tamm-Horsfall protein in type 1 (insulin-dependent) diabetes mellitus using a simplified enzyme linked immunoassay. AB - The relationship between glomerular and tubular dysfunction and metabolic control in type 1 diabetes was studied. To that end the urinary excretion rates of albumin and Tamm-Horsfall protein as well as HbA1c levels were measured in 58 patients with different degrees of diabetic nephropathy and in 76 apparently healthy subjects matched for sex and age. The urinary Tamm-Horsfall protein levels were measured by a simplified enzyme linked immunoassay. The intra- and interassay variations were 8.9% and 13.6%, respectively. The intraindividual variation was 41% and the sensitivity of the assay was 4 micrograms/l. The Tamm Horsfall protein excretion rate was 42.1 x/2.0 micrograms/min (geometric mean x/tolerance factor) in the diabetic patients compared to 34 x/1.9 micrograms/min in the control subjects (NS). The diabetic patients had higher albumin excretion rate (38.5 x/7.3 micrograms/min) than the control subjects (4.7 x/2.3 micrograms/min; P less than 0.001). By using multivariate analysis of variance, HbA1c level was found to be the only independent variable associated with Tamm Horsfall protein excretion rate in diabetic patients (r = -0.28; P = 0.04), while no relationship was found between Tamm-Horsfall protein excretion rate and age, age at onset and duration of diabetes, gender, serum creatinine, diuresis, urinary albumin excretion rate, systolic and diastolic blood pressure levels and antihypertensive treatment. The urinary albumin excretion rate was associated with diastolic blood pressure (r = 0.34; P = 0.02) but not with HbA1c levels when testing the above variables by multivariate analysis of variance. In conclusion, these results may indicate a lack of relationship between glomerular and tubular dysfunction. The former was influenced only by diastolic blood pressure levels and the latter only by the degree of metabolic control. However, the correlations were weak and do not provide any insight into what is actually responsible for glomerular and tubular dysfunction. PMID- 1521340 TI - Influences of diet and surgical trauma on serum alkaline DNase activity levels. AB - Changes in serum alkaline DNase activities might predict the therapeutic response in various malignant diseases. A decrease in serum alkaline DNase activity within days from the onset of therapy has been related to tumour necrosis and may be a possible sign of clinical response to effective treatment. To study if changes in serum alkaline DNase activity could be induced by non-tumour related tissue destruction, sera were collected on several occasions perioperatively in 18 patients undergoing surgery for benign gynaecological disease. Thirty apparently healthy women served as the control group. A significant decrease (P less than 0.001) in serum alkaline DNase activity was observed after an overnight fast in both groups of women. In contrast to the control women, the operated patients showed a significant decrease (P less than 0.001) in serum alkaline DNase activity throughout the operative period and 1 week postoperatively. We conclude that serum alkaline DNase activity is influenced by dietary factors as well as surgical trauma. These factors may limit the clinical usefulness of SADA in patients with cancer. PMID- 1521341 TI - Limitations of the triolein breath test. AB - Patients being investigated for intestinal absorptive capacity were classified as normals or malabsorbers on the basis of three fat absorption tests. Malabsorbers were further classified as mild, moderate, severe or gross according to severity of malabsorption. Using this classification system the triolein breath test was evaluated in 53 patients. Seventeen patients were excluded because their graph of percentage breath [14C]carbon dioxide versus time was exponential indicating that the peak [14C]-carbon dioxide may be occurring later than the six hour duration of the test. The sensitivity and specificity of the triolein breath test were found to be 100% and 96%, respectively and moderate correlations with the individual fat absorption tests were found. However, the breath test was limited in its capacity to predict the severity of malabsorption. Carbon dioxide output was also measured in order to determine the applicability of using an assumed value. The respiratory quotient and variability of results were high in nineteen patients indicating possible hyperventilation. In 32 patients with reproducible results and normal respiratory quotients the average carbon dioxide output was 8.66 mmol/kg per hour with a wide range of 5-12.4 mmol/kg per hour. Consequently the use of an assumed carbon dioxide output can introduce considerable errors in the triolein breath test. This study highlights drawbacks of the triolein breath test, particularly problems in using an assumed carbon dioxide output for its calculation, its inability to predict the severity of malabsorption and the nature of the dietary load used. PMID- 1521342 TI - An enzyme-linked immunosorbent assay for heparin cofactor II (HCII). Application to the measurement of HCII in clinical materials. AB - Heparin cofactor II (HCII) is a thrombin inhibitor in human plasma, the activity of which is enhanced by heparin and dermatan sulfate. To measure the plasma antigen concentration of HCII, an enzyme-linked immunosorbent assay (ELISA) has been developed, and this is based on the use of polyclonal anti-HCII IgG, both as the antigen-capturing antibody and as the labelled antibody. The intra- and inter assay reproducibilities have been calculated to be less than 6%. HCII antigen concentrations evaluated with this ELISA technique in clinical plasma samples correlated well with those determined by electroimmunodiffusion and with HCII activities evaluated using a functional assay (r = 0.909 and r = 0.930, P less than 0.0001). Since the correlation between HCII deficiency and thrombosis is still a controversial issue, the ELISA technique described in this report could be a useful tool for the large-scale studies needed to determine the prevalence of HCII deficiency in healthy individuals and in patients with a history of thrombosis. PMID- 1521343 TI - Selenium and glutathione peroxidase variations induced by polyunsaturated fatty acids oral supplementation in humans. AB - Serum and erythrocyte selenium, erythrocyte and platelet glutathione-peroxidase (GSH-Px) activities, and erythrocyte reduced glutathione (GSH) content were measured in 25 healthy adult individuals before and after daily supplementation with 20 ml of fish oil for 10 weeks. Serum-Se decreased from 0.83 +/- 0.01 mumol/l to 0.75 +/- 0.02 mumol/l (mean +/- S.E.M.) (P less than 0.01); erythrocyte-Se decreased from 4.39 +/- 0.17 nmol/g hemoglobin (Hb) to 2.83 +/- 0.15 nmol/g (P less than 0.001). GSH-Px activities increased both in erythrocytes (6.93 +/- 0.24 iu/g vs 8.18 +/- 0.27 iu/g Hb, P less than 0.01) and in platelets (69.2 +/- 2.8 iu/g vs 90.9 +/- 3.6 iu/g protein, P less than 0.001). The concentration of GSH in erythrocytes fell from 9.56 +/- 0.29 mumol/g Hb to 5.90 +/- 0.30 mumol/g Hb (P less than 0.001). The effects on plasma lipids were evident only for triglycerides (before 1.96 +/- 0.16 mmol/l, after 1.75 +/- 0.14 mmol/l, P less than 0.001). We hypothesise the enrichment of erythrocyte and platelet membranes with polyunsaturated fatty acids (PUFAs), following fish oil intake, can generate increased amounts of lipid peroxides and thus allosterically activate GSH-Px: with time this is harmful for the integrity of the enzyme molecule and Se release may result. We suggest that the Se status of individuals given PUFAs is assessed before and during intake; Se supplements should only be given when serum and/or erythrocyte Se are reduced. PMID- 1521344 TI - Characterization of 6-hexadecanoylamino-4-methylumbelliferyl-beta-D- galactopyranoside as fluorogenic substrate of galactocerebrosidase for the diagnosis of Krabbe disease. AB - 6-Hexadecanoylamino-4-methylumbelliferyl-beta-D-galactopyranoside (HMGal) has been shown to be a specific fluorogenic substrate of galactocerebrosidase and to facilitate the simple enzymatic diagnosis of Krabbe disease in human patients and in twitcher mice. HMGal hydrolysis at pH 4.5 is optimally stimulated by sodium taurocholate (0.25%) and oleic acid (0.05%) with a Km of 0.150, 0.04 and 0.03 mM, respectively for control mouse kidney, human fibroblasts and leukocytes. In control samples, the specific activity (nmol/mg prot./h) for HMGal is higher than for the natural substrate, galactocerebroside, and is severely deficient in the twitcher mouse and in patients with Krabbe disease. Comparative investigation of galactocerebrosidase activity in fibroblasts, leukocytes and brain with radioactive and fluorogenic substrates reveals a good agreement between the results of the two methods. Galactocerebroside (Gal-Cer) is a competitive inhibitor of HMGal hydrolysis in mouse kidney homogenates while GM1-ganglioside has no inhibitory effect in the same assay system. The sensitivity and specificity of this fluorogenic substrate for galactocerebrosidase provides a simple and rapid method for the diagnosis of Krabbe disease, and for the purification of this enzyme from normal tissues. PMID- 1521346 TI - Gastroparesis: diagnostic and therapeutic strategies. AB - Impairment of gastrointestinal motility is common among patients with chronic dyspepsia. Gastroparesis can lead to devastating clinical consequences including malnutrition, weight loss, metabolic acidosis and psychological dysfunction. In this article, the current concepts of gastric motor function are reviewed and the diagnostic and treatment modalities of gastroparesis are discussed in detail. PMID- 1521345 TI - Effects of unsaturated and saturated dietary plant sterols on their serum contents. AB - Rapeseed oil fed to 24 hypercholesterolemic patients (50 g/day) reduced serum cholesterol (-8.5%) and cholestanol concentrations but increased those of campesterol and sitosterol. Continuation of rapeseed oil alone or with added sitosterol (625 mg/day) or sitostanol (630 mg/day) had no further effect on serum cholesterol. Rapeseed oil with sitosterol increased further its own proportion to cholesterol in serum but reduced that of campesterol while rapeseed oil with sitostanol reduced the proportions of both sitosterol and campesterol proportionately to the pretreatment values. The changes in the campesterol and sitosterol proportions were negatively and positively related to each other during the sitosterol and sitostanol additions, respectively. Thus, concentrations of unsaturated plant sterols in serum reflect their dietary intakes, saturated plant sterols are virtually not absorbed, plant sterols interfere with absorption of unsaturated structurally different plant sterols and cholestanol, and plant sterol-induced reduction of sterol absorption may be positively related to absorption efficiency of sterols. PMID- 1521347 TI - Infantile hypertrophic pyloric stenosis. AB - This is a world-wide disease, more common in Caucasians and probably on the increase. The aetiology remains very poorly understood. Presentation is between 2 and 8 weeks with vomiting, classically projectile, in an otherwise well hungry child. The diagnosis can confidently be made in most cases by a careful test feed; ultrasound and barium meal examinations are only required for difficult cases. Intravenous fluid replacement is essential prior to surgery and 24 h or longer may be required to correct acid base disturbances and enable safe general anaesthesia. Pyloromyotomy (Ramstedt's operation) remains the only satisfactory treatment, our mortality rate for this is 0.4%. Occasional vomits occur postoperatively in over half of patients but we are sceptical of the value of graded postoperative feeding regimens. There are no known long-term sequelae to surgery and this remains a most rewarding paediatric surgical condition to treat. PMID- 1521348 TI - Polyps of the stomach and duodenum: significance and management. AB - Gastric and duodenal polypoid lesions are almost always diagnosed incidentally and constitute a clinical problem for treatment and follow-up. The histologic types of polypoid lesions in stomach and duodenum are described, as well as the clinical setting in which they are found. Endoscopy and directed biopsies, but particularly diathermic snare polypectomy, are essential to establish a certain histologic diagnosis. Guidelines are given for treatment and follow-up. PMID- 1521349 TI - Raised liver enzymes in asymptomatic patients: investigation and outcome. AB - Asymptomatic patients with raised liver enzymes are frequently encountered in clinical practice. The commonest lesion in such patients appears to be fatty liver, which may be found in those only modestly overweight. Proven treatments other than abstention from alcohol and weight loss are available for approximately 20% of asymptomatic people with abnormal liver enzymes. However, if experimental therapies are taken into account this would rise to over 50%, making an early accurate diagnosis important. Most conditions can be diagnosed non invasively, especially in those people with markedly abnormal transaminases. The recent introduction of new non-invasive tests decreases the need for liver biopsy for diagnostic purposes, however liver biopsy retains an important role in establishing patient prognosis and response to treatment. PMID- 1521350 TI - Lactic acid bacteria in the gut in normal and disordered states. AB - The human gut flora is a complex and finely balanced ecosystem which plays an important protective role in humans. Although relatively stable, its composition may be altered in various disease states and by the administration of antimicrobial agents. Preparations containing viable lactic acid bacteria of human origin appear to have value in restoring normal microbial function and alleviating symptoms in some patients with gastrointestinal infection and other conditions. PMID- 1521351 TI - Insulin-like growth factor 1 and growth hormone in chronic liver disease. AB - Somatomedins or insulin-like growth factors (IGF) are peptides synthesized in the liver. IGFs have different anabolic and metabolic actions and are important in normal growth and development. The concentration of insulin-like growth factor 1 (IGF-1) is low in patients with chronic liver disease mainly due to the decreased liver function. Low levels of somatomedins are also seen in patients with growth hormone (GH) insufficiency, renal impairment, and malnutrition. GH stimulates the production of IGF-1, and both are part of a negative feedback system acting on hepatic, pituitary, and hypothalamic levels. The basal and stimulated GH concentration is pathologically elevated in patients with chronic liver disease and may be due to a disturbed regulation. Alterations in liver IGF receptors in patients with chronic liver disease still require investigation as they may be important for the liver function. PMID- 1521352 TI - Fish oil feeding selectively attenuates contractile responses to noradrenaline and electrical stimulation in the perfused mesenteric resistance vessels of spontaneously hypertensive rats. AB - 1. The mechanism of the antihypertensive effects of n-3 fatty acids were examined in spontaneously hypertensive rats (SHR) by feeding 'Max EPA' fish oil or hydrogenated coconut oil and determining the responses of perfused mesenteric resistance vessels to various contractile agents and peri-arterial nerve stimulation. 2. Fish oil feeding for 4 weeks caused a decrease in the responses to exogenous noradrenaline and electrical nerve stimulations but had no significant effect on vasopressin and KCl (80 mmol/L) induced contractions. 3. These results provide direct evidence for specific attenuation of vascular responses to sympatho-adrenal stimulation in resistance vessels following fish oil feeding and may account for the antihypertensive effects seen in humans and in some forms of hypertension in rats. PMID- 1521353 TI - Propofol anaesthesia in malignant hyperpyrexia susceptible swine. AB - 1. Malignant hyperpyrexia (MH) is an inherited muscle abnormality that presents clinically as a syndrome of life-threatening complications during general anaesthesia. 2. Propofol is a new sedative hypnotic used for the induction and maintenance of anaesthesia. 3. Propofol did not induce MH in five susceptible pigs. Propofol did not induce contracture in isolated MH susceptible muscle but did modify halothane, caffeine and KCl contractures. PMID- 1521355 TI - Renal handling of endogenous lithium in experimental diabetes mellitus in the rat. AB - 1. The usefulness of determining the renal handling of endogenous lithium as a marker of proximal tubular sodium reabsorption was assessed in streptozotocin induced diabetes mellitus in the Sprague-Dawley rat. 2. The clearance and fractional excretion of lithium were determined before and following the development of diabetes mellitus, and compared with measurements of proximal tubular reabsorption made directly using micropuncture techniques. Endogenous lithium was measured in order to avoid the toxic tubular effects of exogenously administered lithium salts. 3. Although a trend existed for a reduction in the fractional excretion of lithium in diabetic animals (1.8 +/- 0.3 vs 2.4 +/- 0.5%; P greater than 0.20), this did not reach statistical significance and did not accurately reflect the change in directly measured tubular Na reabsorption. 4. The decrease in proximal tubular Na reabsorption demonstrated in diabetic animals treated with phlorizin was not significantly reflected in the fractional lithium excretion, although again a corresponding trend was evident (1.9 +/- 0.8 vs 0.6 +/- 0.2%; P greater than 0.10. 5. In summary, the significant alterations in tubular Na handling in diabetes mellitus, previously demonstrated directly using micropuncture techniques, are not reflected in the renal handling of endogenous lithium. This indirect method is inadequate to assess proximal tubular Na transport in experimental diabetes mellitus. PMID- 1521354 TI - Cardiovascular habituation to emotional stress in Lyon hypertensive rats. AB - 1. Intra-aortic blood pressure was recorded continuously in freely moving genetically hypertensive (LH), normotensive (LN) and low blood pressure (LL) rats of the Lyon strain during two 11 h periods (08:00-19:00 h). During the first period (control), the animals were left undisturbed and during the second period (stress), a jet of air was applied for 20 min every hour. Urine was collected simultaneously and analysed for its content in norepinephrine and epinephrine. 2. The first exposure to the stressor induced larger increases in blood pressure and heart rate in LH than in LN and LL rats. However blood pressure and heart rate responses to the 10 following stressors decreased in LH rats while they remained stable in LN and LL animals. 3. Repeated stress exposure induced significant increases in epinephrine excretion in both LN and LL but not in LH rats. 4. It is concluded that LH rats exhibit marked cardiovascular habituation to repeated stress. Taken together with the lack of stress-induced sympathoadrenal activation, this suggests a reduced level of emotional responsiveness in Lyon hypertensive rats. PMID- 1521356 TI - High Blood Pressure Research Council of Australia Annual meeting. Adelaide, 12-13 December 1991. PMID- 1521357 TI - Enalapril decreases plasma noradrenaline levels during the cold pressor test in human hypertensives. AB - 1. The effects of the angiotensin-converting enzyme (ACE) inhibitor enalapril on the responses of blood pressure and plasma catecholamine levels to the cold pressor test in human hypertensives were examined. 2. Systolic and diastolic blood pressure decreased significantly after treatment with enalapril (5 mg/day for 4 weeks) as did the resting level of plasma noradrenaline. 3. The cold pressor test induced a rise in blood pressure and plasma noradrenaline levels. After 2 and 4 weeks enalapril treatment, the rises in the plasma noradrenaline level and systolic and diastolic pressure due to cold pressor test were reduced significantly. 4. These results suggest that ACE inhibition has a sympatho inhibitory effect. One possible explanation is that enalapril reduces angiotensin II formation thus decreasing the activation of release-enhancing angiotensin II receptors on postganglionic sympathetic nerve endings. PMID- 1521358 TI - Effects of repeated doses of pseudoephedrine on blood pressure and plasma catecholamines in normal subjects and in patients with phaeochromocytoma. AB - 1. Increases in blood pressure (BP) and in plasma noradrenaline concentration (NA) were observed after two doses of a non-prescription decongestant containing pseudoephedrine (PE) in two of three patients with phaeochromocytoma, before but not after removal of the tumour. The pressor response was terminated by oral phenoxybenzamine, and modified by prior exposure to this drug. 2. In eight normal subjects administration of the same two doses prevented falls in BP and in NA usually seen with prolonged recumbency, but neither BP nor NA increased. However, a pressor response was observed in a normal subject with a strong family history of hypertension. 3. Exposure to PE in non-prescription decongestants is not without risk in hypertension. PMID- 1521359 TI - Is isolated systolic hypertension a 'white coat' phenomenon in the elderly? AB - 1. Repeated clinic blood pressure measurement was compared with non-invasive ambulatory blood pressure (ABP) monitoring in 10 elderly subjects with isolated systolic hypertension (ISH) and 11 normotensive controls (NT). 2. Subjects were assessed on four occasions at weekly intervals. None was receiving antihypertensive or vasoactive medication. 3. Mean clinic blood pressure was consistently higher than mean daytime ABP in both clinical groups. This effect was greater for systolic (SBP) than diastolic blood pressure (DBP) and in the ISH group compared with the NT group. The reproducibility of the clinic minus ABP difference was high in both groups; the mean +/- s.d. of the differences was 26 +/- 15/9 +/- 2 mmHg in the ISH group and 7 +/- 18/8 +/- 9 mmHg in the controls. 4. ABP readings were normally distributed for both SBP and DBP in both groups. In the ISH group, the frequency distribution of SBP readings was shifted to the right whilst the distribution of DBP readings overlapped that of the NT subjects. 5. These results suggest a pressor response may largely account for the elevated SBP seen in elderly subjects with sustained ISH based on casual readings. PMID- 1521360 TI - Sample size requirements for clinical trials of isolated systolic hypertension. AB - 1. This study investigated components of blood pressure variability in elderly subjects with isolated systolic hypertension (ISH) using both ambulatory blood pressure monitoring (ABPM) and casual clinic blood pressure measurement. These were then used to determine sample size requirements for clinical trials of different designs. 2. Eleven elderly subjects not receiving antihypertensive medication were seen on four occasions at weekly intervals. On each occasion blood pressure was measured in the clinic and then for 24 h using a non-invasive ABPM device. Nested analysis of variance was used to calculate the 'between subject' and 'between subject within occasion' components of blood pressure variability. 3. Increasing the number of readings or occasions where measurement was performed in a parallel group trial only reduced the variability substantially when the number of subjects involved was less than 50. Use of a cross-over design substantially reduced the sample size required. 4. ABPM appears most useful as a strategy for reducing sample size in parallel group trials in ISH involving small numbers of subjects measured on one occasion. PMID- 1521361 TI - Concurrence of primary aldosteronism and renal artery stenosis. AB - 1. An unusual clinical case is described in which renal artery stenosis (RAS) was found to coexist with adrenocortical hyperplasia, resulting in hypertension. 2. Partial relief of the hypertension was achieved by correction of RAS, and then further relief by extirpation of one adrenal gland affected by unilateral hyperplasia, in interventions 8 months apart. 3. Biochemical features typical of primary hyperaldosteronism were observed both before and after RAS repair but were not present after unilateral adrenalectomy. 4. The association of these two lesions could have occurred by chance, through genetic linkage, or by progression from RAS to tertiary aldosteronism. PMID- 1521362 TI - Inaccuracy of electronic sphygmomanometers. AB - 1. Eight electronic sphygmomanometers were purchased locally and evaluated for clinical accuracy during blood pressure recording on volunteer patients. 2. Direct comparisons of systolic and diastolic pressure were made in seven devices using a Y-tube connection to a mercury sphygmomanometer, simultaneous measurements being made by a trained observer on 16-18 subjects. 3. Indirect comparisons were made for all eight devices by comparing the average values obtained from all measurements made on each subject by the device with the average value from mercury sphygmomanometric readings made over the same time period. 4. Results were analysed by measuring the mean and standard deviation of the differences between device readings and mercury readings. Published criteria were used to grade the devices. 5. The most accurate machine was the Omron HEM 719K, which used the cuff as a sound sensor and had an internal microphone. The least accurate was the Omron HEM-812F, which used a finger-cuff method. The other devices (all oscillometric) ranged from fair to poor in performance accuracy. PMID- 1521363 TI - Familial hyperaldosteronism type II: five families with a new variety of primary aldosteronism. AB - 1. Thirteen patients from five families had Familial Hyperaldosteronism Type II (FH-II), a new variety of familial primary aldosteronism not suppressible with dexamethasone that often involves adrenocortical adenoma formation. 2. Five patients had solitary aldosterone-producing adenomas, three had bilateral autonomous overproduction of aldosterone, and in five the subtype is yet to be determined. 3. Comparing FH-II patients with 88 patients with primary aldosteronism of other causes revealed no differences in mean age at presentation or at onset of hypertension, sex incidence, lowest recorded serum potassium, plasma aldosterone, plasma renin activity or adenoma size. 4. Analysis of DNA in peripheral blood of patients with FH-II, their affected and unaffected relatives, and in removed tumours is in progress in order to determine the underlying genetic defect(s) in FH-II, perhaps an abnormality in the P-450aldo gene (CYP11B2). 5. It is recommended that hypertensive relatives of patients with primary aldosteronism should have measurements of the aldosterone/renin ratio. PMID- 1521364 TI - Population-based survey of human sodium and potassium excretion. AB - 1. During the 1989 National Heart Foundation Risk Factor Prevalence Survey a subsample in Hobart collected 24 h urine samples to measure electrolyte excretion. 2. The ranges were 30-344 mmol/24 h for Na+ excretion (mean 160 mmol/24 h for men, 124 mmol/24 h for women), and 25-119 mmol/24 h for K+ excretion (mean 77 mmol/24 h for men, 68 mmol/24 h for women). 3. As in other surveys, women excreted about 20-25% less Na+ and K+ than men, although there was no significant sex difference in the ratio of Na+/K+ excretion. 4. The recommended dietary intake (RDI) for Na+ and K+ was followed simultaneously by 19% of subjects, and 13% had a 24 h urinary Na+/K+ ratio less than or equal to 1.0. 5. Observance of the RDI limited the value of iodized salt for goitre prophylaxis. 6. Sodium excretion rates were outside the therapeutic range of thiazide diuretics in 22% of subjects. 7. Diet groups for long-term prospective cohort studies to test the prophylactic value of avoiding salt could apparently be recruited from existing subsamples of the population. PMID- 1521365 TI - Axonal projections from respiratory centres towards the rostral ventrolateral medulla in the rat. AB - 1. Efferent pathways from brainstem respiratory centres towards bulbospinal tyrosine hydroxylase immunoreactive neurons were identified in the rat using a combination of electrophysiology, retrograde and anterograde tract-tracing, and immunohistochemistry. 2. Varicose axons originating from respiratory centres were found in close apposition to bulbospinal tyrosine hydroxylase immunoreactive neurons in the ventrolateral medulla. 3. These findings support the idea that respiratory rhythms in sympathetic nerves may be due to a synaptic connection between brainstem respiratory neurons and bulbospinal tyrosine hydroxylase immunoreactive neurons of the C1 cell group. PMID- 1521366 TI - Haemodynamic changes in the Moncada model of atherosclerosis. AB - 1. The application of a non-constricting silastic cuff to the rabbit common carotid artery (CCA; n = 5) results in intimal thickening within 7 days. 2. Ultrasonography showed kinking of the CCA at the cuff edges, as well as a 13% arterial narrowing (P less than 0.02) within the cuffed segment, both at days 1 and 7. Correspondingly, the time averaged diastolic Doppler velocity (TAV) was 68.8 +/- 12.8% higher (P less than 0.025) in the cuffed region in comparison with that 1 cm proximal (P 1 cm) on day 1, and 54.2 +/- 11.5% higher at day 7 (P less than 0.05). TAV values along control silastic strips were not significantly changed. 3. There was a significant increase (P less than 0.025) in intimal area within the cuffed region (0.098 +/- 0.024 mm3) compared with both the proximal control (0.014 +/- 0.001 mm3) and with that over control silastic strips (0.021 +/- 0.004 mm3, P less than 0.01). 4. Medial area within the cuff (0.433 +/- 0.017 mm3) was decreased (P less than 0.005) compared with P 1 cm control (0.602 +/- 0.069 mm3). 5. There was gross peri-arteritic thickening involving the adventitia along the non-constricted cuffed segment. Importantly, it was also noted alongside the control silastic strip. 6. Kinking of the CCA and associated vasoconstriction cause changes in blood flow velocity along even a non constricting cuff, and this may explain the intimal thickening previously noted in this experimental model. The peri-arteritic changes, on the other hand, appear to be a reaction to the silastic itself. PMID- 1521367 TI - Polymerase chain reaction-based DNA fingerprinting in the spontaneously hypertensive rat: potential source of cDNA library probes. AB - 1. Using the Polymerase Chain Reaction with a primer homologous to a repetitive unit found at irregular distances in the rat genome, we were able to synthesize DNA fragments spanning such units and visualize them as a ladder of discrete bands following electrophoresis. 2. Differences between fingerprint patterns generated using SHR, WKY and SD DNA, in the form of band deletions or duplications, were readily detected. 3. Unlike traditional fingerprinting, PCR fingerprints allow the ready extraction and characterization of polymorphic bands. Such bands could then be used as probes with which to screen a cDNA library that might, in turn, identify expressed genes involved in the development of hypertension. PMID- 1521368 TI - The heterogeneity of 11-beta-hydroxysteroid dehydrogenase activities in the rat hippocampus implies a complex regulation of steroid hormone action. AB - 1. The rat hippocampus 11-beta-hydroxysteroid dehydrogenase (11-HSD) displays a different substrate specificity to that of other tissues. S1 nuclease analysis was used to determine whether the hippocampal messenger RNA is different from that found in other tissues. 2. S1 nuclease analysis using probes spanning the full length cDNA demonstrated that there were no differences in sequence between the hippocampal 11-HSD and the enzyme originally cloned from the liver. 3. These results suggest that there may be multiple 11-HSD isoforms in the hippocampus with different substrate specificities. PMID- 1521369 TI - DA-1 receptors mediate renal effects of the dopamine prodrug, gludopa, in conscious rabbits. AB - 1. Eight male rabbits were implanted with Doppler flow probes around the lower abdominal aorta and left renal artery. A 2 week recovery period was allowed prior to the experiment. 2. Normal saline, gludopa at 25 micrograms/kg per min and at 100 micrograms/kg per min were each infused i.v. for 60 min. One week later the same protocol was administered to four of these animals in addition to DA-1 antagonist SCH 23390 (0.3 mg/kg i.v.) before gludopa infusion. 3. Gludopa elicited significant increases in urine flow, urinary sodium excretion and renal blood flow, and decreased renal vascular resistance. These changes were abolished by the DA-1 antagonist. Blood pressure, heart rate and hindlimb blood flow remained unchanged. 4. Urine dopamine excretion was increased 1200-fold and 7800 fold after gludopa administration at 25 micrograms/kg per min and 100 micrograms/kg per min, respectively, while plasma dopamine concentration and plasma renin activity (PRA) were not significantly altered. However, PRA was elevated by gludopa with DA-1 antagonism. 5. The renal vasodilation, natriuresis and diuresis produced by gludopa in conscious rabbits appears to be mediated by locally generated dopamine via DA-1 receptors. PMID- 1521370 TI - Effect of enalapril on body sodium and handling of a sodium chloride load in hypertensive and normotensive rats. AB - 1. The effect of enalapril on handling of an Na load and on body Na during 96 h of zero Na intake was measured in hypertensive rats (GH and SHR) and their normotensive controls (N and WKY) by a whole body counting method. 2. Enalapril treatment led to a greater fall in body Na in the first 24 h after the Na load (as expected from the known effect of ACE inhibition on aldosterone production) and thus to a slightly faster excretion of an amount equivalent to the load. 3. Enalapril-treated rats were unable to maintain body Na on a zero Na intake. This was also expected from the known effect on aldosterone production, though other mechanisms are not excluded. The effect was more marked in the SHR and WKY than in GH and N but there was no significant difference in this effect between the hypertensives and their respective control strains. PMID- 1521371 TI - Renal vasoconstriction is modulated by nitric oxide. AB - 1. The effect of the nitric oxide synthesis inhibitor, NG-nitro-L-arginine (NOLA), has been examined on vascular reactivity in the rat isolated perfused kidney. 2. NOLA (10 mumol/L) had no effect on basal perfusion pressure, but significantly enhanced the vasoconstrictor responses to sympathetic nerve stimulation (1-16 Hz, 10 s) and noradrenaline (10-300 pmol). The enhancements were greater with the lower frequencies of stimulation and lower doses of noradrenaline. 3. The enhancing effect of 10 mumol/L NOLA on vasoconstrictor responses to nerve stimulation was partially prevented by 100 mumol/L L-arginine while 100 mumol/L D-arginine had no effect. 4. The results suggest that nitric oxide attenuates vasoconstrictor responses in the rat kidney, and provide evidence that nitric oxide has a physiological role in the modulation of vascular reactivity. PMID- 1521372 TI - Differential regulation by transforming growth factor-beta 1 of platelet-derived growth factor-stimulated proliferation of vascular smooth muscle cells from SHR and WKY rats. AB - 1. This study has examined and compared the time-course of action of transforming growth factor-beta 1 (TGF-beta 1) on platelet-derived growth factor-BB-stimulated proliferation of vascular smooth muscle cells isolated from normotensive Wistar Kyoto (WKY) rats and spontaneously hypertensive rats (SHR). 2. Transforming growth factor-beta 1 inhibited vascular smooth muscle cell proliferation stimulated by platelet-derived growth factor-BB in WKY rats by approximately 60 75%. 3. In contrast, transforming growth factor-beta 1 potentiated an 8-35% growth factor action on cell proliferation in the SHR. 4. Defects in transforming growth factor-beta 1 action may be part of the molecular mechanism responsible for the development of vascular hypertrophy in the SHR. PMID- 1521373 TI - Labor management. PMID- 1521374 TI - Labor after prior cesarean section. AB - 1. All women with PCS should be considered candidates for vaginal delivery. Certain high-risk factors then should be used to recommend elective repeat cesarean section. Currently, a scar in the active segment of the uterus is considered an absolute contraindication to labor. 2. Women should be informed of the chances of success (which in most instances are excellent), course of action in labor, and the rare risk of uterine rupture. 3. Women in a very low risk category (one low-transverse PCS) should be managed like any laboring patient but including fetal monitoring. 4. The remaining laboring patients may benefit from more intensive intrapartum surveillance, including continuous electronic fetal monitoring, early rupture of the fetal membranes, and placement of an intrauterine pressure catheter. 5. The labor course in women with PCS will depend on the number of vaginal deliveries achieved previously and the stage of labor reached before the cesarean section was done. 6. Labor disorders in patients with PCS, as in all patients, should be diagnosed and managed promptly. 7. Neither oxytocin nor epidural use is contraindicated in these patients. As in any patient, care should be taken to avoid iatrogenic uterine hyperstimulation. 8. Uterine rupture may have many different presentations. However, the most common is abnormal fetal heart rate patterns that are especially variable or prolonged decelerations. 9. Most uterine ruptures can be repaired and do not require hysterectomy. Hysterectomy may be the appropriate choice in some situations. 10. A history of a prior uterine rupture is not a contraindication to future childbearing, but it may place the woman at greater risk for a repeat event. PMID- 1521375 TI - Effects of analgesia on labor. AB - Uterine activity may be defined in terms of the frequency of contractions of the uterus and the pressure generated by these contractions. Most studies that report an effect of analgesia on labor are retrospective, and, if prospective, are nonrandomized. Drug effects on uterine activity and labor progress are probably dose related, but are also influenced by a myriad of other factors including, but not limited to, the mother's emotional state, degree of cervical change, uterine contractility pattern, phase of labor, and individual differences in pharmacokinetics and drug sensitivity. The latest phase of labor may be prolonged by excessive narcotic or inappropriate timing of regional analgesia. The normal active phase tends to be resistant to the inhibitory effects of the usual amount of any analgesia. A brief period of decreased uterine activity often follows institution of analgesia. This may effectually accelerate labor in some patients by decreasing maternal anxiety and serum concentrations of catecholamines. A combination of sedation epidural blockade, and subsequent oxytocin use may prove effective in correcting a dysfunctional or hyperstimulatory pattern during the active phase. The second stage of labor may be slightly prolonged by effective epidural analgesia, but this delay is not necessarily harmful as long as the fetal heart rate tracing is normal, maternal hydration is adequate, and maternal pain relief is sufficient. PMID- 1521376 TI - Oxytocin for the induction or augmentation of labor. PMID- 1521377 TI - Cervical ripening. PMID- 1521378 TI - Operative vaginal delivery in the 1990s. PMID- 1521379 TI - Molecular biology of uterine contractility. PMID- 1521380 TI - Issues in fluid management during labor: general considerations. PMID- 1521381 TI - Issues in fluid management during labor: maternal plasma volume status and volume loading. PMID- 1521382 TI - Ultrasonography in labor. PMID- 1521383 TI - Amniotomy and maternal position in labor. PMID- 1521384 TI - Assessment of uterine contractility and activity. PMID- 1521385 TI - Vaginal breech delivery in the 1990s. PMID- 1521386 TI - Evaluation of the fetal-pelvic relationship. PMID- 1521387 TI - Issues in the diagnosis and research of premenstrual syndrome. AB - The diagnosis of PMS depends on the identification of a core symptom complex, including behavioral symptoms of either irritability, accompanied by an internal state of anxiety or depression, and fatigue. (Fatigue is the most common symptom of PMS.) At least one core physical symptoms, bloating of the abdomen or extremities, breast tenderness, and headache also is required to establish the diagnosis. Although these core symptoms are required, none is pathognomonic for the disorder and the timing of the symptoms with respect to the menstrual cycle also must be established. This can only be done accurately using valid and reliable prospective recording instruments, such as COPE. Personality factors, the degree of psychosocial stress faced by the woman, and biochemical markers have little utility in establishing the diagnosis. The literature with respect to the prevalence of PMS in the population, effective treatments for the disorder, and the diagnosis of the disease must be interpreted by recognizing the inclusion in these studies of women with comorbid psychiatric disease, invalid and unreliable symptom inventories, and inadequate characterization of menstrual cycle phases. There are sociologic reasons why the true prevalence and treatment response to interventions may not be seen by the clinician. Nonetheless, the availability of effective treatment for the disorder necessitates accurate diagnosis of the syndrome based on the strict criteria presented. Additional research founded on the development of psychoneuroendocrine models is likely to provide insight into both the pathophysiology and treatment alternatives for PMS. PMID- 1521388 TI - Female-specific mood disorders. AB - Hormones are partial determinants of certain sexually dimorphic behaviors and interact with psychosocial, environmental, and other physiologic factors. The part played by sex hormones in the direct control of overt human behavior is, compared with that found in lower animals, slight and less readily definable. In humans, these hormones, although necessary for maintenance of libido and sexual behavior, seem to control the intensity of such behavior rather than its direction. In most women of reproductive age, the different phases of the menstrual cycle are not associated with major physical or psychologic discomfort. Some women actually report positive changes during the premenstrual period. Only 5-10% of women in this age group have changes in mood, sleep, eating habits, level of energy, and physical symptoms that appear to be linked temporally to the late-luteal phase of the cycle. It is plausible to assume that women with LLPDD are vulnerable to the menstrual cycle as a Zeitgeber. In these women, a cascade of events triggered originally along the HPG axis brings about the shift from an existing vulnerability to the actual manifestations of LLPDD and other forms of female-specific mood disorders. The degree of vulnerability becomes apparent at puberty when girls are exposed to increasing estrogenic influences. Particularly vulnerable times are the periods that mark shifts in the reproductive stages (menarche, the premenstruum, puerperium, and menopause), periods associated with major hormonal turmoil and psychosocial stresses. A conditioning-sensitization model has been described to explain the longitudinal course of affective disorders, and it also has been proposed for PMS. According to this model, even low levels of psychosocial stress are capable of triggering episodes of dysphoria in vulnerable previously sensitized subjects. LLPDD is associated strongly with a lifetime diagnosis of major depression, and the concurrent comorbidity in these women is also high. Future epidemiologic studies on depression should consider the effects of female-specific Zeitgeber on mood disorders in the populations studied. PMID- 1521389 TI - Neuroendocrinology of premenstrual syndrome. PMID- 1521390 TI - The role of serotonin in premenstrual syndrome. PMID- 1521391 TI - Clinician's approach to the diagnosis and management of premenstrual syndrome. PMID- 1521393 TI - Role of psychotropic medication in the treatment of affective symptoms in premenstrual syndrome. PMID- 1521392 TI - Hormonal manipulation in the treatment of premenstrual syndrome. PMID- 1521394 TI - Critical evaluation of nutritional factors in the pathophysiology and treatment of premenstrual syndrome. PMID- 1521395 TI - Cognitive model of premenstrual syndrome. PMID- 1521396 TI - A retrospective of normal oral healthcare procedures vs. power brush/jet lavage with a corroborative study. AB - The efficacy of power brushes and/or oral irrigating devices in comparison to manual brushing has been the subject of study and controversial results for some thirty years. Recently, a well-designed study has reported that carefully taught, consistently reinforced and monitored toothbrushing combined with necessary professional intervention is as effective as power brushing with and without oral lavage. Because the usual individual in the work-a-day world cannot or will not indulge regularly in these elaborate procedures, a simple, small sample test of comparative efficacy was done and submitted to a paired analysis. Results demonstrated that not only are these power devices as good as demonstrated by the reported studies, but also are superior for the type of patient most often encountered in daily practice--the person who does not or who cannot comply completely with instructions and who cannot constantly be monitored for compliance. PMID- 1521397 TI - A clinical study on the control of dental plaque using an electronic toothbrush with piezo-electric element. AB - A double-blind clinical study was conducted to compare the plaque-removing efficiency of a newly designed electronic toothbrush to that of a placebo, conventional toothbrush. Twenty-six students were selected at Asahi University, School of Dentistry in Japan. The subjects were divided into two groups, one which used the electronic toothbrush and the other which used the placebo toothbrush. The subjects served as their own control by brushing manually for 3 minutes. The plaque elimination ratio, however, showed no significant difference between the testing and the control group. The main conclusion of this study is that an electronic toothbrush is not superior to the conventional toothbrush. PMID- 1521399 TI - Improved diagnostics: clinical evaluation of a color-coded, polymeric periodontal probe. AB - The objective of this study was to compare the accuracy, reproducibility and patient comfort of a newly designed, color-coded, polymeric periodontal probe to a traditional, color-coded metal probe. Twenty-four adult subjects with varying degrees of periodontal disease (from slight to severe) reported for two visits, one week apart. A randomization schedule for probe use was adopted over the two visits so that the gingival crevices in two quadrants were probed with the same probe (metal or polymeric) providing reproducibility information for each probe, while the other two quadrants were probed first with one probe then the other for comparison data yielding information on accuracy. A bleeding index was obtained using the same schedule. Clinical scoring was performed by the same examiner. After probing each quadrant, subjects rated discomfort using a visual analog scale (VAS). Results showed no significant difference in depth readings greater than 2 mm between the polymeric and metal probes (3.41 +/- 0.37 mm vs. 3.38 +/- 0.32 mm, p = 0.55). Significantly less discomfort (assessed by VAS) was recorded by patients after polymeric probe use (3.70 +/- 2.40 cm vs. 4.44 +/- 2.49 cm, p = 0.015). The bleeding index indicated significantly less bleeding with the polymeric probe (0.80 +/- 0.56 vs. 1.24 +/- 0.65, p = 0.0001). Both the polymeric and metal probes were found to produce highly reproducible results in all measures across visits. PMID- 1521398 TI - Effectiveness of three mouthrinses to inhibit acid formation by dental plaque under home-use conditions. AB - A study was conducted to assess the effectiveness of three mouthrinses (Plax, Cepacol and Fluordent) to inhibit acid formation from plaque collected from 21 volunteer dental students. Plaque was collected on each side of the mouth, two hours after breakfast, once-a-week, after a period of 48 hours without any oral hygiene other than the use of the mouthrinses. Initial pH and the change in pH of plaque incubated with sucrose were recorded up to 120 min. Excepting Cepacol for the first week only, no inhibitory effect on acid formation was observed. PMID- 1521400 TI - Sickle-cell anemia: a case report and literature review. AB - Sickle-cell disease is characterized by the pathophysiological features of chronic hemolytic anemia, vaso-occlusion resulting in ischemic tissue injury and painful episodes. The organs at greatest risk are the spleen, kidney and bone marrow, where oxygen tension is low and blood flow is diminished. However, disease may also present in the mandible. The oral manifestations and radiographic findings of a sickle cell patient with a left mandibular neuropathy, along with dental management guidelines are presented in the context of interdisciplinary care. PMID- 1521401 TI - Diabetes control during bowel cleansing with PEG-electrolyte solution. PMID- 1521402 TI - Treatment of adult acute leukemia. AB - The epidemiology, etiology, pathophysiology, classification, and clinical appearance of adult acute leukemia are reviewed, and treatment strategies are discussed. Some 18,000 Americans die of leukemia each year, with acute leukemia account for half of these deaths. The etiology of acute leukemia is unknown, but current theories propose that the disease is caused by environmental factors acting on a genetically susceptible host. Acute leukemia occurs when a single hematopoietic precursor cell undergoes neoplastic transformation; autonomous proliferation of the leukemia clone continues until the patient dies of infection or bleeding. Acute leukemias are broadly classified as myelogenous and lymphocytic on the basis of cell lineage. Signs and symptoms are related to infiltration of the bone marrow by leukemic cells and the resultant failure of normal hematopoiesis. Therapy for acute myelogenous leukemia includes remission induction and consolidation with an array of antineoplastic agents. Allogeneic or autologous bone marrow transplantation is the therapy of choice for eligible patients in the first complete remission. Neither low-dose maintenance therapy nor prophylaxis for CNS involvement is indicated. Therapy for acute lymphocytic leukemia includes induction, consolidation, maintenance, and CNS prophylaxis. Allogeneic bone marrow transplantation should be reserved for standard-risk patients in second or subsequent complete remission and for high-risk patients in first remission. Intensive combination chemotherapy and bone marrow transplantation have improved the outlook for many adult patients with acute leukemia. PMID- 1521403 TI - White clot syndrome and thrombocytopenia: reasons to abandon heparin i.v. lock flush solution. PMID- 1521404 TI - Dapsone-induced methemoglobinemia and hemolytic anemia. AB - The treatment of two common adverse effects of dapsone (methemoglobinemia and hemolytic anemia) is discussed, and a case of acute dapsone intoxication is described. A pregnant 29-year-old woman was admitted to an emergency room three hours after ingesting 50 tablets of dapsone (100 mg each) and six alcoholic drinks. One hour after admission 50 g of activated charcoal was given p.o., and 65 mg of methylene blue was given i.v. The patient was found to have a methemoglobin concentration of 25.1%. Arterial blood gases while the patient was breathing 4 L/min of oxygen by nasal cannula were PO2, 136 mm Hg (72.1% saturation); PCO2, 28.9 mm Hg; bicarbonate content, 18.9 mmol/L; and pH, 7.42. Oxygen therapy was changed to 100% oxygen by face mask, 50 g of activated charcoal in sorbitol was administered p.o., and another 65 mg of methylene blue was given i.v. Two more 50-g doses of activated charcoal in sorbitol were given (18.5 and 22 hours after dapsone ingestion). Methylene blue 130 mg was given 14 hours after dapsone ingestion, and 65 mg was given 21, 36, and 55.5 hours after ingestion. Methemoglobin concentrations never rose above 20% after the sixth dose of methylene blue. On hospital days 2 and 3, laboratory values were consistent with a diagnosis of hemolytic anemia; the patient received two units of packed red blood cells. The hematocrit decreased over the next three days to 23.9%, and the patient received four units of packed red blood cells.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1521405 TI - Apparent potentiation of warfarin activity by tetracycline. PMID- 1521406 TI - Criteria for use of amphotericin B bladder irrigation in adult inpatients. PMID- 1521407 TI - Breathing disorders in sleep. PMID- 1521408 TI - The role of upper airway anatomy and physiology in obstructive sleep apnea. AB - Research efforts to date have determined that both anatomic and physiologic variables may contribute to the pathophysiology of OSA. Whether specific factors within either of these two categories will be shown to predominate remains to be seen. Surely, experience with sleep apnea patients teaches us that different variables are important in different OSA patients. However, even those patients who initially appear to have predominantly an anatomic or physiologic cause of their OSA often fail to respond to specific treatment. Treatment failure implies the following: (1) The initial impression of the importance of a given variable was wrong. This may happen in the patient who has a narrow transpalatal airway and fails to respond to uvulopalatopharyngoplasty. In this individual, physiologic variables such as pharyngeal collapsibility or periodic breathing may need to be addressed. Of course, the reverse may occur; patients may be treated pharmacologically for an assumed physiologic mechanism and important anatomic factors may have been overlooked. Our ability to differentiate the importance of these different variables is poor. Therefore, our diagnostic acumen needs further refinement. (2) Of course, it is likely that the proper diagnosis was made, but the therapy chosen was imperfect. In the area of anatomy, investigators are just beginning to try surgical approaches designed specifically for the pharyngeal site of obstruction. In other words, uvulopalatopharyngoplasty is not the best approach for everyone. In physiology, treatments beyond continuous positive airway pressure will be needed. It is hoped that advances in the pharmacology of sleep disorders will establish more convenient and successful therapies. It is likely that OSA is a heterogenous disease process. We must realize that a treatment that helps one patient may not be applicable to the next individual. Through a better understanding of the pathophysiology of OSA, better treatment modalities should be developed, resulting in improved quality of life for OSA patients. PMID- 1521409 TI - Upper airway imaging in relation to obstructive sleep apnea. AB - A variety of imaging techniques have been used to assess upper airway size and function in patients with OSA. Each technique has certain advantages and limitations. Many of the imaging techniques study awake and upright patients, whereas OSA typically occurs while the patient is asleep in the supine position. Upper airway imaging may identify specific upper airway abnormalities that cause OSA. Furthermore, the majority of patients with OSA have a narrow and more collapsible airway in the velopharynx. Upper airway occlusion during sleep usually starts in the velopharynx and extends caudally. Obesity results in both extrinsic upper airway narrowing and soft tissue enlargement. Upper airway edema may occur secondary to OSA and subsequently exacerbate the OSA by causing further upper airway narrowing. Upper airway imaging provides some insights into the mechanism of action of certain treatments and is increasingly used to help direct treatment. Weight loss reduces upper airway collapsibility. Nasal CPAP increases upper airway size and reduces upper airway edema. UPPP enlarges the oropharynx and reduces upper airway collapsibility. Patients with a narrow upper airway, particularly relative to tongue size, have a good response to UPPP. PMID- 1521410 TI - Evaluation of daytime sleepiness. AB - In summary, the evaluation of the tired patient requires an awareness of the various meanings of tiredness. Furthermore, it is important to differentiate normal sleepiness that is a product of circadian rhythm variation in vigilance from pathologic sleepiness. Sleepiness that results from faulty habits, e.g., altered sleep scheduling, drugs, or sleep restriction, can be readily discerned with the aid of a sleep-wake diary. Because subjective sleepiness is often unappreciated, especially in patients with sleep apnea, methods that rely on self ratings of the severity of sleepiness, e.g., visual analogue scale, 10-cm line, or SSS may not coincide with performance tasks, observer assessments, or such physiologic methods as the MSLT. Less commonly employed neurophysiologic methods include pupillometry and averaged evoked potentials. On the other hand, the MSLT is commonly used for the detection of physiologic sleepiness. Moreover, it is helpful in evaluating response to treatment. A variation of the MSLT, the MWT, which instructs the individual to remain awake, does not discriminate between sleep onset times for wakefulness and the MSLT for sleepiness in normal subjects. The MWT may be useful for the assessment of treatment responses for excessive daytime sleepiness, e.g., narcolepsy, and for determining the frequency of daytime sleep episodes. The differences that have been observed between behavioral measures and physiologic measures of sleepiness suggest that these techniques assess different aspects of sleepiness. HLA typing (DR2, DQw1) has been shown to be a useful method for corroborating narcolepsy-cataplexy, but the antigens are neither specific for the disorder nor for sleepiness alone. PMID- 1521411 TI - Driving performance and automobile accidents in patients with sleep apnea. AB - Patients with untreated obstructive sleep apnea have poorer driving performance than patients without sleep apnea. This poor driving has been demonstrated by studies on a wide variety of driving simulators. Patients with sleep apnea show a significant improvement in driving performance after successful treatment of their apnea with nasal CPAP. After treatment with CPAP, their driving performance is similar to control subjects. Several studies show that patients with untreated sleep apnea are poor drivers and have two to three times more auto accidents than other drivers. These studies reveal that almost one quarter of these patients report frequently falling asleep while driving. Patients with severe sleep apnea or those who perform poorly on driving simulators may be at highest risk of auto accidents. Automobile accidents involving patients with sleep apnea may lead to severe injury or death. Patients, individual physicians, and the medical profession have responsibilities to help prevent these accidents. Finally, more study is needed to improve patient care, protect drivers, and formulate a fair and rational policy concerning drivers with sleep apnea. PMID- 1521412 TI - Hypertension, cardiac arrhythmias, myocardial infarction, and stroke in relation to obstructive sleep apnea. AB - The cyclical changes in heart rate and systemic blood pressure that accompany apneic events are predominantly mediated by fluctuations in the activity of the autonomic nervous system. Increased vagal efferent parasympathetic activity is responsible for the cyclical reductions in heart rate during apnea. In contrast, the cyclical elevations in systemic blood pressure are believed to result from recurrent peripheral vasoconstriction mediated by repetitive activation of the sympathetic nervous system. Maximal activation and pressures coincide with apnea termination and brief arousal from sleep. These cyclical elevations in systemic pressure during sleep increase ventricular workload and, thereby, may contribute to the development of ventricular hypertrophy. Systemic hypertension is present during wakefulness in approximately 50% of patients with OSA. Although age and obesity are the predominant risk factors for diurnal hypertension, OSA probably makes an independent contribution in younger obese men. Sinus bradycardia, Mobitz type 1 second-degree heart block, and prolonged sinus arrest have all been documented in association with the apneic events. Increased ventricular ectopy has been observed with oxyhemoglobin desaturations below 60%. Myocardial ischemia, infarction, sudden death, and stroke all demonstrate similar circadian variations in time of onset. Peak frequencies occur between 6 AM and noon, generally within several hours of awakening. Although sleep is associated with decreased frequencies of these adverse cardiovascular events in the general population, evidence exists linking REM sleep to an increased risk of myocardial ischemia. In men who habitually snore, epidemiologic data have detected an increased risk for ischemic heart disease and stroke. Habitual snoring has also been associated with an increased risk of sudden death during sleep. In patients with clinically significant OSA, there is reasonable information indicating excessive mortality in the absence of treatment. This mortality is predominantly cardiovascular and tends to occur during sleep. PMID- 1521413 TI - Right and left ventricular functional impairment and sleep apnea. AB - Obstructive sleep apnea may contribute to the development of pulmonary hypertension and RVF primarily through pulmonary vasoconstriction secondary to hypoxia. Several recent studies indicate, however, that intermittent apnea related hypoxia is not sufficient to cause sustained pulmonary hypertension. These studies have been consistent in showing that pulmonary hypertension and RVF are almost invariably seen in the presence of diurnal hypoxia. Sustained pulmonary hypertension, therefore, appears to be associated with sustained hypoxia as is the case in COPD. Patients with OSA who have hypoxia while awake are, as a rule, obese and have mild-to-moderate diffuse obstructive airways disease. Thus, most cases of pulmonary hypertension in association with OSA result from a combination of OSA, obesity, and diffuse obstructive airways disease, a so-called overlap syndrome. However, from the therapeutic viewpoint, it is apparent that treatment of OSA by NCPAP or tracheostomy, in such cases, is usually sufficient to reverse pulmonary hypertension and RVF. More recent work has provided strong evidence that OSA can play a role in the pathogenesis of LV heart failure in patients with CHF of otherwise unknown etiology. It is likely that this occurs through a combination of increased LV afterload related to exaggerated negative Pit swings during obstructive apneas, to intermittent hypoxia, and to chronically elevated sympathoadrenal activity. Reversal of OSA by NCPAP in these patients may relieve LV heart failure. These findings add a new dimension to our understanding of the pathophysiologic effects of OSA on the cardiovascular system by demonstrating that the LV is a structure that may suffer functional impairment secondary to the stresses imposed by OSA. Finally, it has now become apparent that CSR in patients with CHF can cause symptoms of a sleep apnea syndrome when associated with intermittent hypoxia and arousals from sleep. Reversal of CSR during sleep by NCPAP can lead to alleviation of these symptoms and possibly to reduced cardiac dyspnea and LV systolic function as well. Taken together, this suggests that much more extensive use of polysomnography may be warranted in the investigation of cardiovascular disease. The reasons are compelling: sleep apnea disorders are common and eminently treatable conditions whose reversal can result in improved right and left heart function and symptomatic improvement in patients with impaired myocardial function. PMID- 1521414 TI - Management of obstructive sleep apnea. AB - Although the indications for treatment of obstructive sleep apnea are controversial, there is general agreement that treatment is warranted in patients with a combined apnea and hypopnea frequency of 20 events per hour of sleep. General therapeutic measures include abstinence from alcohol and weight loss in obese patients. A minority of patients with specific abnormalities of the nose, pharynx, or jaw may require surgical management. In the absence of specific upper airway abnormalities, the most effective treatment is nasal continuous positive airway pressure or, if necessary, bilevel positive airway pressure during sleep. The role of uvulopalatopharyngoplasty remains controversial, due in part to the reported variability in long-term efficacy of this procedure. Drug therapy may be effective in selected patients. PMID- 1521415 TI - Central sleep apnea. AB - The critical issue in considering the diagnosis and management of CSA is to determine the physiologic process underlying the disorder. CSA includes a pathophysiologically and clinically heterogeneous group of disorders that can be divided into two main groups on the basis of the awake PaCO2: a hypercapnic group, in whom the disorder is related to central alveolar hypoventilation or neuromuscular disease, and a nonhypercapnic group, in whom there is no identifiable underlying disorder. The common feature of these two groups is recurrent episodes of central apnea during sleep related to withdrawal of the wakefulness drive to breathing. In the hypercapnic group the clinical history is dominated by recurrent episodes of respiratory failure and its complications, with the sleep disturbance being a secondary feature. CSA in these patients is simply an exaggeration, by sleep, of their hypoventilation disorder. Treatment in most cases involves mechanical assisted ventilation during sleep, which can be very effective in reversing CSA and respiratory failure. In contrast, idiopathic CSA is characterized by a tendency to hyperventilation. This tendency is reinforced during sleep by recurrent arousals, which tend to propagate the CSA. Unlike hypercapnic CSA, idiopathic CSA is a relatively benign condition in which cardiorespiratory failure is not a feature. Treatment of this disorder is problematic, but the use of nocturnal nasal CPAP appears to be quite effective. PMID- 1521416 TI - Hypoventilation: neuromuscular and chest wall disorders. AB - Patients with neuromuscular and chest wall disorders are vulnerable at night when alterations in ventilatory mechanics and control associated with their disease are imposed on the changes in mechanics and control associated with sleep. The physiologic and clinical consequences of these events may be reversed by nocturnal mechanical ventilatory support. PMID- 1521417 TI - Nocturnal hypoxemia in patients with chronic obstructive pulmonary disease. AB - Marked hypoxemia occurs during REM sleep in patients with chronic obstructive pulmonary disorder. This article deals with the mechanisms, pathophysiologic consequences, and treatment of REM hypoxemia. PMID- 1521418 TI - Nocturnal asthma. AB - The nocturnal worsening of asthma is a common problem that can have significant related morbidity and mortality. There are many circadian biologic rhythms that contribute to the increased nocturnal bronchial reactivity and decrement in lung function. Therapy directed at the nocturnal aspect of this asthma process can produce marked improvement in symptoms and lung function. PMID- 1521420 TI - Reproductive medicine and the clinical laboratory. PMID- 1521419 TI - Use of the laboratory in infertility and recurrent spontaneous miscarriage. AB - The laboratory is an important contributor to patient evaluation for infertility or recurrent spontaneous miscarriage. Hormonal determinations, cultures for microorganisms, andrology tests, immunologic tests, karyotype analysis, and histopathology are valuable components of laboratory evaluation. The use of clinical laboratory tests must be integrated with other clinical and radiologic studies. PMID- 1521421 TI - In vitro fertilization. Technology and methods. AB - The laboratory component of assisted reproductive technologies involves the manipulation and culture of male and female gametes in vitro, with the goal of producing viable embryos for transfer to a woman to enable the establishment of pregnancy. The biology of the gametes and resulting embryos dictates how they should be handled in vitro to maximize their potential at establishing a viable pregnancy. This article examines the biology of gametes and offers some suggestions as how best to proceed with the process of in vitro fertilization, embryo culture, and embryo transfer. PMID- 1521423 TI - Linkage analysis and predicting genetic disease. AB - Linkage analysis is an important and clinically applicable method of predicting risk for genetic disorders and traits. When a gene cannot be detected directly, evaluation of a closely linked marker may be used in risk assessment. This review of linkage analysis provides basic information and examples of the application of these methods in genetic counseling situations. PMID- 1521422 TI - The technology, law, and ethics of in vitro fertilization, gamete donation, and surrogate motherhood. AB - This article examines some of the legal, ethical, and policy issues raised by the development and use of technologies for noncoital reproduction: gamete transfer and manipulation, in vitro fertilization, and zygote transfer and manipulation. After briefly describing these technologies, this article examines three closely related concerns raised by their introduction: (1) the effect of new technologies on the social understanding of parenthood and the legal regulation of the family; (2) the impact on women and children of a market in the material and services for producing children; and (3) the rights and interests involved in conflicts over the control and disposition of extrauterine embryos. PMID- 1521424 TI - Prenatal genetics in laboratory medicine. A cytogeneticist's perspective. AB - A concise review of current trends in prenatal genetic diagnosis for the nongeneticist is presented in this article. Its impact on the practice of clinical laboratory medicine today is discussed, and an attempt is made to capture the sense of the growing body of knowledge and excitement in prenatal genetic diagnostic technology, and the fountain of possibilities it has created for prenatal care. PMID- 1521425 TI - What can be learned from cordocentesis? AB - Cordocentesis is a well-accepted procedure that is widely practiced by experienced perinatologists. Its facile and safe access to the fetal circulation has broadened the spectrum of congenital disorders diagnosed prenatally. Some fetal disease states can now be identified and treated earlier, directly, more quickly, and more effectively than before, resulting in improved patient care. Although cordocentesis has been embraced by the perinatal community, it is, by definition, a technique of obtaining a fetal blood sample. A prerequisite for the procedure to exert its full impact on perinatal care is a highly capable clinical laboratory. The facility must be aware of the commonly requested fetal serologic, hematologic, and serum chemistry studies, as well as their normal values. Efforts must be made to perform fetal blood studies rapidly and reliably on small specimens. Laboratory personnel should be familiar with the indications and pitfalls of these tests and those that are best referred to a specialty laboratory. A general understanding of the perinatologist's needs and concerns will lead to a cooperative working relationship between clinician and laboratory. In this manner, we will truly discover what can be learned from cordocentesis. PMID- 1521426 TI - Laboratory diagnosis of fetal infections. AB - In utero infections of the fetus can lead to significant morbidity and mortality in the newborn child. The signs and symptoms of clinical disease, however, do not always suggest a given pathogen. The laboratory must be able to provide an early and accurate diagnosis of the causative agent so that prompt and appropriate antimicrobial therapy and medical care can be initiated. The scope of this article includes the methods employed by the laboratory to assist in the diagnosis of bacterial, fungal, parasitic, and viral infections of the fetus. Where appropriate, detection methods were addressed for the diagnosis of the major pathogens responsible for infection during the birth process. PMID- 1521427 TI - Maternal immunity to red cell antigens and fetal transfusion. AB - This article has presented an overview of developments in the treatment of HDN. The number of cases requiring treatment that have occurred in the last decade has dropped because of the development and implementation of Rh immunoprophylaxis, although this treatment still appears to be underutilized in the United States. Failure to recognize the need for immunoprophylaxis in certain situations (including unrecognized abortion) has led to a small residual population of alloimmunized mothers who will require comprehensive treatment during subsequent pregnancies. Alloimmunization to other red cell antigens remains a small but significant problem in other women. Although great advances have been made in the monitoring of these pregnancies, amniotic fluid analysis remains a mainstay for the third-trimester evaluation of alloimmunized pregnancies. Noninvasive methods such as ultrasound evaluation and the monocyte assays may supplement, but cannot entirely replace, the need for direct assessment. The most striking advancement in the evaluation and treatment of these infants has been the ability to access the fetal circulation directly through intravenous umbilical cord sampling. This method allows for an immediate assessment of fetal anemia as well as a route for direct fetal transfusion. The method has also permitted a more complete assessment of fetal physiology. However, the method may be overutilized at the present time and has some degree of risk to the fetus, even in experienced hands. Additional methods of treatment for the alloimmunized pregnancy include plasma exchange, intravenous immunoglobulin infusion, and promethazine hydrochloride. The popularity of plasma exchange has probably decreased with the advent of more direct fetal sampling and treatment techniques, but it may be useful in the treatment of first-trimester pregnancy losses. Intravenous immunoglobulin and promethazine hydrochloride appear to be promising alternatives that require more investigation. It is apparent that efforts need to be channeled towards prevention of HDN in a health system that is highly aware of increasing costs and the benefits of preventive medicine. PMID- 1521428 TI - Neonatal alloimmune thrombocytopenia. AB - Neonatal alloimmune thrombocytopenia is caused by the transplacental passage of maternal antibodies directed against platelet-specific antigens. Because complications from bleeding may result, prompt institution of therapy may be necessary. Accurate diagnosis by serologic techniques permits appropriate therapy to be administered both prenatally and postnatally. PMID- 1521429 TI - Hemapheresis in pregnancy. AB - Plasma exchange in pregnancy has benefited those diseases that occur and are treated in the nonpregnant patient. In addition, special emphasis was given to diseases unique to pregnancy, such as hemolytic disease of the newborn, which is significantly modified by plasma exchange therapy. Fluid volumes, replacement solution, and techniques were discussed. PMID- 1521430 TI - Assessment of fetal lung maturity by laboratory methods. AB - I have reviewed many of the methods available for the assessment of fetal lung maturity. The difficulty of using diagnostic tests for diseases of low prevalence has been discussed. By reviewing the nature of the amniotic fluid surfactant material, and some of the principles underlying analytical methods, the bases of some of the recurring methodologic problems have been pointed out. It is concluded that a number of reasonably straightforward tests will provide information of essentially the same utility as more costly, difficult, and time consuming assays commonly employed. PMID- 1521431 TI - Could American intensivists learn from their Japanese colleagues? PMID- 1521432 TI - Use of extracorporeal life support in patients with congenital heart disease: state of the art? PMID- 1521433 TI - Extracorporeal life support: issues of who, when, why, and how. PMID- 1521434 TI - Acidosis of cardiopulmonary resuscitation: carbon dioxide transport and anaerobiosis. PMID- 1521435 TI - An initial comparison of intensive care in Japan and the United States. AB - OBJECTIVE: The objective of this study was to compare the utilization of, and outcome from, critical care services in selected medical centers providing secondary and tertiary care in the United States and Japan. DESIGN: Prospective data collection on 1,292 patients from each of the participating Japanese study hospitals in 1987 to 1989 and compared with the 5,030 patients in the United States 1982 Acute Physiology and Chronic Health Evaluation (APACHE II) database used to develop the APACHE II equation. Detailed organizational characteristics of the participating ICUs and hospitals were also obtained. SETTING: Data collection took place in the ICUs of 13 U.S. hospitals and six Japanese hospitals. PATIENTS: Data were collected on consecutive, unselected patients from medical, surgical, and mixed medical/surgical critical care units, with a spectrum of medical and surgical diagnoses. MEASUREMENTS AND MAIN RESULTS: U.S. and Japanese ICUs have a similar array of diagnostic and therapeutic modalities. Only 2% (range 0.6 to 3.5) of beds in Japanese hospitals were designated to intensive care. The organization of the Japanese and U.S. ICUs varied by hospital. There were significantly fewer women admitted to Japanese ICUs and a substantially lower proportion of low-risk-of-death patients. Despite a rapidly aging population, there were relatively fewer elderly patients with chronic health ailments in the Japanese ICU population (8%) compared with the U.S. cohort (18%). CONCLUSIONS: In this sample of hospitals, similar high-technology critical care is available in the United States and Japan. Variations in utilization between the two countries represent differences in case mix and bed availability. The APACHE II equation stratified patients in the Japanese patient cohort across the full spectrum of increasing severity of illness. PMID- 1521436 TI - Use of extracorporeal life support in patients with congenital heart disease. AB - OBJECTIVES: To review a large experience with extracorporeal life support in patients with congenital heart disease. To determine the major causes of mortality and morbidity in order to improve the results of using this technology in this patient population. DESIGN: Retrospective chart review. PATIENTS: Twenty five patients between the ages of 1 day and 8 yrs. These patients had congenital heart disease and were clinically felt to be at high risk for death caused by cardiac failure or by respiratory failure complicated by congenital heart disease. INTERVENTIONS: All patients in this report were placed on extracorporeal life support to allow recovery of myocardial or pulmonary function. MEASUREMENTS AND MAIN RESULTS: Of these 25 patients, 52% were weaned from bypass support and 40% survived to discharge. Patients who were not weaned from extracorporeal life support characteristically suffered from irreversible neurologic injury, multiple organ failure, or bleeding complications. Only one patient died of irreversible cardiac failure. CONCLUSIONS: Extracorporeal life support can be useful in supporting patients with congenital heart disease with life-threatening cardiac or pulmonary failure. Improvements in limiting neurologic and bleeding complications may lead to improvements in the use of extracorporeal life support for this indication. However, prospective, randomized studies are needed to appreciate the role of extracorporeal life support in these patients. PMID- 1521437 TI - Acute hypoxemic respiratory failure in infants and children: clinical and pathologic characteristics. AB - OBJECTIVE: To examine the clinical and pathologic features of acute hypoxemic respiratory failure in children. DESIGN: Retrospective review of medical records and pathologic material during a 44-month period. SETTING: Multidisciplinary pediatric ICU. PATIENTS AND METHODS: With the assistance of a computerized database, the medical records of 2,254 pediatric ICU admissions were evaluated to identify children with respiratory failure. Children with acute hypoxemic respiratory failure who met the following definition were selected for inclusion: a) PaO2 less than 75 torr (less than 10.0 kPa) with an FIO2 of greater than 0.5; b) diffuse bilateral infiltrates on chest radiograph; and c) exclusion of cardiogenic pulmonary edema clinically or by pulmonary artery catheterization. Patients were excluded if they did not receive tracheal intubation and assisted ventilation. The medical records were reviewed for demographic, clinical, and physiologic information. Pathologic findings from autopsy or lung biopsy were also reviewed. Patients were placed in one of six groups based on their underlying disorder. In addition, the presence of neutropenia, septic shock, or a history of bone marrow transplantation was noted as a coexisting condition. MAIN RESULTS: A total of 100 acute hypoxemic respiratory failure patients were identified (4.4% of all 2,254 pediatric ICU admissions; 50 male, 50 female). Mean age was 6.0 +/- 5.4 (SD) yrs (range 1 month to 18 yrs). The overall mortality rate was 72%. The mortality rate was not affected by the underlying disorder, but it was higher in the presence of septic shock (80% vs. 58%; odds ratio 2.8), neutropenia (88% vs. 64%; odds ratio 4.0), and bone marrow transplantation (95% vs. 66%; odds ratio 10.4). When multivariate regression analysis was performed using all coexisting conditions, human immunodeficiency virus status, and patient gender, only a history of bone marrow transplantation and gender appeared to affect outcome. Oxygenation ratio (PaO2/FIO2), alveolar-arterial oxygen tension difference, duration of exposure to high levels of oxygen, and airway pressure measurements indicated more severe derangement of pulmonary function in those patients who died. Cardiac function was similar in survivors and nonsurvivors. Respiratory failure occurred in 32 children with severe neutropenia (mean absolute neutrophil count 55 +/- 101 cells/mm3), including 16 children with an absolute neutrophil count of 0. Pulmonary tissue from 37 children was studied. Diffuse alveolar damage was observed in 24%; morphologic evidence of infectious pneumonitis was encountered in an additional 41%. CONCLUSIONS: Children with acute hypoxemic respiratory failure represent a heterogeneous subset of patients. In our group of patients, infectious pneumonitis was more commonly encountered than diffuse alveolar damage. The mortality rate of children with acute hypoxemic respiratory failure has not improved since 1980. PMID- 1521438 TI - Effects of tolazoline and prostacyclin on pulmonary hypertension in infants after cardiac surgery. AB - OBJECTIVE: To evaluate the hemodynamic effects of tolazoline and prostacyclin in infants with pulmonary vasospasm after cardiac surgery. DESIGN: Prospective cohort study. SETTING: Pediatric ICU. PATIENTS: The cohort consisted of 42 infants and children with congenital heart disease and pulmonary hypertension who underwent corrective surgery and were monitored postoperatively using pulmonary artery catheters. Fourteen infants (2 to 12 months old) in this group required postoperative treatment with tolazoline or prostacyclin. INTERVENTIONS: Tolazoline was administered as a bolus of 0.5 mg/kg for treatment of persistent pulmonary hypertension or acute pulmonary hypertensive crisis. If its effectiveness was proved after 30 mins by hemodynamic measurements, a continuous iv infusion of 0.5 mg/kg/hr was established. Higher doses of tolazoline were avoided. If tolazoline treatment did not fulfill the criteria for pulmonary vasodilation, prostacyclin was given by continuous iv infusion at a starting rate of 5 ng/kg/min, followed by 10 ng/kg/min. In three patients, the infusion rate was increased to 15 ng/kg/min. RESULTS: Bolus administration of tolazoline resulted in a distinct pulmonary vasodilation in seven infants: mean pulmonary artery pressure and pulmonary vascular resistance decreased by an average of 35% and 45%, respectively. In these patients, tolazoline was infused over the following 12 to 72 hrs. One infant who received tolazoline for 72 hrs developed a clinically important gastrointestinal hemorrhage. In seven nonresponders to tolazoline, prostacyclin (PGI2) at an infusion rate of 5 ng/kg/min led to pulmonary vasodilation in five patients, at an iv infusion rate of 10 ng/kg/min in all seven infants studied. The latter dose of PGI2 reduced the mean pulmonary artery pressure by an average of 37%, and pulmonary vascular resistance by 43%. Transient withdrawal of prostacyclin in five infants demonstrated its short half life and clinical effectiveness. Apart from a facial flush, no side-effects were encountered using PGI2 as an infusion over durations ranging from 12 to 504 hrs. CONCLUSIONS: These data suggest that, if tolazoline in a relatively low dose proves to be inefficient, prostacyclin can still be used as a safe and effective drug for treatment of pulmonary vasospasm. Prostacyclin offers more than a pharmacologic alternative to increased tolazoline dosages. PMID- 1521439 TI - Relationship between infusion rates, plasma concentrations, and cardiovascular and metabolic effects during the infusion of norepinephrine in healthy volunteers. AB - OBJECTIVE: To determine the relationship between iv infusion rate, plasma concentrations, and hemodynamic and metabolic actions of norepinephrine. DESIGN: Norepinephrine was administered by using five iv infusion rates (0.01 to 0.2 micrograms/kg/min) for 30 mins each to eight volunteers, for the purpose of constructing cumulative plasma concentration-response curves. SETTING: Laboratory of the Department of Anesthesiology at a university hospital. MEASUREMENTS AND MAIN RESULTS: Systolic and diastolic BP, heart rate, and the plasma concentrations of norepinephrine, glucose, nonesterified fatty acids, and insulin were measured at the end of each infusion rate. During the highest infusion rate, plasma norepinephrine concentrations increased from 199 +/- 75 to 7475 +/- 1071 pg/mL (1.18 +/- 0.44 to 44.18 +/- 6.33 nmol/L). Typical hemodynamic responses, such as increases in BP and decreases in heart rate, were seen, while the plasma concentrations of glucose and nonesterified fatty acids increased from 92 +/- 10 to 132 +/- 17 mg/dL (5.1 +/- 0.6 to 7.3 +/- 0.9 mmol/L) and 11 +/- 4 to 34 +/- 6 mg/dL (0.11 +/- 0.04 to 0.34 +/- 0.06 g/L), respectively, during the 0.2 micrograms/kg/min infusion rate (p less than .05). Despite the increase in glucose concentration, insulin remained at baseline values. Metabolic and hemodynamic effects occurred at similar plasma concentrations throughout the study. CONCLUSIONS: Administration of norepinephrine showed no selective hemodynamic actions. The metabolic responses observed in this investigation were similar to those responses seen during increased endogenous sympathetic nervous system activity, such as stress, exercise, or trauma. PMID- 1521440 TI - Factors related to quality of life 12 months after discharge from an intensive care unit. AB - OBJECTIVE: To perform an analysis of the quality of life of survivors after ICU discharge. DESIGN: Prospective study. SETTING: Medical-surgical ICU of a Spanish reference hospital. PATIENTS: Patients (n = 606) admitted in a 6-month period. METHOD: A questionnaire regarding quality of life issues was completed at the time of admission by patients or surrogates (n = 606). The questionnaire was given again 12 months after ICU discharge to 444 surviving patients. Both questionnaires evaluated the patient's ability to function and communicate for the previous 3 months. A Quality of Life score of 0 corresponded to no limitations. An increasing score indicated a reduction in function. A score of greater than 10 points implied a severe physical handicap. Information was also collected on the severity of illness and the diagnosis that prompted ICU admission. RESULTS: The mean Quality of Life score of all survivors worsened from a mean of 4.62 at the time of ICU admission to a mean of 6.11 at 12 months after ICU discharge (p less than .01) and was most evident for patients greater than 75 yrs of age (from a mean of 6.33 to a mean of 9.54). However, patients with the highest initial Quality of Life scores had a significant improvement at 12 months (14.61 +/- 0.50 to 12.48 +/- 0.78 points [p less than .05]). A higher severity of illness score corresponded to a higher Quality of Life score, but a multivariate analysis indicated that the factors with the greatest influence on the post discharge Quality of Life score were the initial Quality of Life score and age. CONCLUSIONS: Twelve months after discharge from the ICU, a patient's functional status, as measured by the Quality of Life score, is influenced most by age and their Quality of Life score at the time of ICU admission. While there is an overall decrease in the Quality of Life score for survivors, admission and treatment in an ICU do not always result in deterioration of the Quality of Life score. This study indicates that Quality of Life scores could become a routine part of patient evaluation. PMID- 1521441 TI - DNR or CPR--the choice is ours. AB - OBJECTIVE: To assess changes in the terminal care of critically ill patients before and after the institution of do-not-resuscitate (DNR) order policies, and policies on the care of the hopelessly ill. DESIGN: Retrospective chart review that comprises the following groups: 82 consecutive deaths from 1981 to 1982, representing our older practice pattern of frequent utilization of terminal resuscitative efforts (group A); 37 consecutive deaths between June and December 1987, the 6-month period immediately preceding the adoption of the DNR policy (group B); and 61 consecutive deaths in calendar year 1988 after the DNR policy went into effect (group C). SETTING: Surgical ICU of a large tertiary care center. PATIENTS: Consecutive patients who died during the study periods before and after the implementation of a DNR policy. INTERVENTIONS: The implementation of hospital-wide policies on DNR orders and care of the hopelessly ill patient. MEASUREMENTS AND MAIN RESULTS: There were no significant differences between the three groups for age, Acute Physiology and Chronic Health Evaluation II scores, Mortality Risk Ratio scores, or lengths of ICU stay. There was a significant (p less than .0001) decrease in the frequency of terminal resuscitative efforts, as evidenced by a decrease from 52% in group A to 3% in group C. The preterminal identification and acceptance of imminent death increased over the study period with an increase (p less than .0001) in the application of DNR orders from 46% in group A to 98% in group C. The ability to withdraw support increased (p less than .0001) from 23% in group A to 73% in group C. CONCLUSIONS: We believe that our data exemplify how our ICU has been able to identify hopelessly ill patients, and how it has implemented specific levels of care that take into account not only medical prognostication, but also the wishes of the patients and their families, while maintaining an atmosphere of comfort and dignity. We demonstrated an important change in the philosophy of care for hopelessly ill patients, which was associated with the institution of DNR policies. PMID- 1521442 TI - Energy expenditure and gas exchange measurements in postoperative patients: thermodilution versus indirect calorimetry. AB - OBJECTIVE: To compare a method of measuring energy expenditure and gas exchange using the Fick principle with the standard indirect calorimetry technique. DESIGN: Prospective study of a consecutive sample of postoperative patients. Oxygen consumption (VO2), CO2 production (VCO2), respiratory quotient, and energy expenditure were derived from measurements of variables, including oxygen content and cardiac output. Energy expenditure and gas exchange were measured simultaneously by continuous indirect calorimetry over a 60-min period. SETTING: Surgical ICU in a university hospital. PATIENTS: Twenty-six consecutive patients (45 to 80 yrs) who underwent sustained surgical trauma. Excluded from the study entry were patients with time-related fluctuations of hemodynamic variables, poor cooperation, patients who required supplemental oxygen, or mechanical ventilation. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: While the measurements of VO2 and VCO2 by calorimetry and thermodilution were significantly correlated with one another (for VO2, r2 = .93, p less than .001; for VCO2, r2 = .26, p less than .01), VO2 and VCO2 values by indirect calorimetry were consistently greater than VO2 and VCO2 values by the Fick method (p less than .01). The respiratory quotient calorimetric measurements ranged between 0.69 and 0.99, whereas the corresponding thermodilution measurements spread to impossible values, from 0.24 to 1.30 (0.821 +/- 0.07 vs. 0.740 +/- 0.24, p less than .05). There was an insignificant relationship (r2 = .06, p = .21) between the values of respiratory quotient by the two methods. A strong, positive correlation between energy expenditure measured by indirect calorimetry and energy expenditure measured by the Fick method was observed (r2 = .92, p less than .001). The limit of agreement between the two methods was -0.24 +/- 73 kcal/day/m2 (-1.00 +/- 305 kJ/day/m2). CONCLUSIONS: In postoperative patients, while VO2 and energy expenditure measurements by thermodilution are easy to perform and accurate for clinical purposes, VCO2, and respiratory quotient measurements are too imprecise and inaccurate to serve any useful function. Therefore, in those clinical situations in which an evaluation of respiratory quotient and substrate utilization may be useful for purposes of metabolic care of the surgical patient, precise measurements of gas exchange with indirect calorimetry are mandatory. PMID- 1521443 TI - Hematologic changes in massive burn injury. AB - OBJECTIVE: To study and report the striking hematologic changes that occur in patients with massive burn injury. DESIGN: Case reports and description of hematologic studies. SETTING: A municipal general hospital burn unit. PATIENTS: Three severely burned patients who survived, respectively, 45 mins, 22 hrs, and 57 hrs after hospitalization. METHODS: Routine clinical hematologic laboratory studies. RESULTS: The patients had intravascular hemolysis, and their RBCs exhibited spherocytosis, fragmentation, and vesiculation. Numerous fragments of red cell membranes were originally present in the blood and cleared within 4 hrs. These fragments may have contributed to the renal failure seen in these patients. The patients also had marked pseudothrombocytosis, presumably owing to "incorrect recognition" by the automatic counter of red cell microvesicles as platelets. CONCLUSIONS: Pseudothrombocytosis should be anticipated with massive burn injury. Despite high or normal platelet counts reported by the laboratory, evidence of intravascular coagulation should be promptly investigated. PMID- 1521445 TI - Prediction criteria for successful weaning from respiratory support: statistical and connectionist analyses. AB - OBJECTIVE: To develop predictive criteria for successful weaning of patients from mechanical assistance to ventilation, based on simple clinical tests using discriminant analyses and neural network systems. DESIGN: Retrospective development of predictive criteria and subsequent prospective testing of the same predictive criteria. SETTING: Medical ICU of a 300-bed teaching Veterans Administration Hospital. PATIENTS: Twenty-five ventilator-dependent elderly patients with acute respiratory failure. INTERVENTIONS: Routine measurements of negative inspiratory force, tidal volume, minute ventilation, respiratory rate, vital capacity, and maximum voluntary ventilation, followed by a weaning trial. Success or failure in 21 efforts was analyzed by a linear and quadratic discriminant model and neural network formulas to develop prediction criteria. The criteria developed were tested for predictive power prospectively in nine trials in six patients. RESULTS: The statistical and neural network analyses predicted the success or failure of weaning within 90% to 100% accuracy. CONCLUSION: Use of quadratic discriminant and neural network analyses could be useful in developing accurate predictive criteria for successful weaning based on simple bedside measurements. PMID- 1521444 TI - Changes in lung function and pulmonary capillary permeability after cardiopulmonary bypass. AB - OBJECTIVE: To assess the possibility that changes in lung function following cardiopulmonary bypass are associated with increased pulmonary capillary permeability. DESIGN: A prospective, descriptive study. SETTING: Adult cardiothoracic ICU in a post-graduate teaching hospital. PATIENTS: Ten sequential patients undergoing cardiac surgery requiring cardiopulmonary bypass. MEASUREMENTS: Arterial blood gas tensions, helium dilution end-expiratory lung volume, and carbon monoxide transfer were measured by a rebreathing technique preoperatively and 2 hrs postoperatively. Lung extravascular protein accumulation index was measured by a double-isotope technique 2 hrs postoperatively and in a group of normal controls. RESULTS: Mean +/- SEM alveolar-arterial PO2 gradient increased from 77 +/- 14 torr (10.3 +/- 1.8 kPa) to 138 +/- 24 torr (18.5 +/- 3.2 kPa) (p less than .01). Functional residual capacity decreased by 20.2 +/- 5.6% (p less than .01). Carbon monoxide transfer decreased by 26.7 +/- 5.3% (p less than .01) for the lung as a whole and by 17.9 +/- 3.2% (p less than .01) per liter of accessible gas volume. Protein accumulation index ranged from 0.03 to 3.2 x 10(-3) (median 0.6) postoperatively (median for normal subjects 0.4; p less than .05), although only one patient had a value indicative of clinically important endothelial injury. CONCLUSIONS: Cardiac surgery involving cardiopulmonary bypass results in a deterioration in lung function characterized by a loss of lung volume, a reduction in carbon monoxide transfer, and an increase in the alveolar-arterial PO2 gradient. These changes do not appear to be mediated by an increase in pulmonary endothelial permeability. PMID- 1521446 TI - Arterial pH and carbon dioxide tension as indicators of tissue perfusion during cardiac arrest in a canine model. AB - BACKGROUND AND METHODS: Previous studies have shown that Paco2 and end-tidal CO2 reflect coronary artery perfusion pressures during cardiac arrest. We investigated the relationship of coronary artery perfusion pressure to central arterial pH and Paco2 values during resuscitation from cardiac arrest in a canine model. Twenty-four mongrel dogs were block randomized to three different resuscitation groups after induction of ventricular fibrillation and cardiac arrest: a) standard cardiopulmonary resuscitation (CPR) and advanced life support (n = 8); b) cardiopulmonary bypass (n = 8); or c) open-chest CPR (n = 8). Central arterial blood gases and perfusion pressures were monitored during cardiac arrest and during resuscitation. RESULTS: Prearrest blood gases and hemodynamic values were similar between groups. Sixteen dogs from all three groups were successfully resuscitated. Survivors had significantly higher coronary artery perfusion pressure (p = .03), Paco2 (p = .015), and lower pH (p = .01) values than nonsurvivors. There was no correlation of pH and Paco2 during mechanical external CPR. However, after institution of the different resuscitation techniques, pH and Paco2 each showed a statistically significant correlation (r2 = .50 and .33, respectively) with coronary artery perfusion pressure. CONCLUSIONS: Central arterial pH and Paco2 monitoring during cardiac arrest may reflect the adequacy of tissue perfusion during resuscitation and may predict resuscitation outcome from ventricular fibrillation. PMID- 1521448 TI - Hyaluronan: relationship to hemodynamics and survival in porcine injury and sepsis. AB - BACKGROUND AND METHODS: Hyaluronan is a polysaccharide normally present in low concentrations in the blood, and is rapidly cleared from the blood by the liver. Increased plasma hyaluronan concentrations have been found in patients with sepsis. We studied changes in serum hyaluronan concentrations and their relationship to hemodynamics and survival in a 48-hr porcine model of injury and sepsis. RESULTS: Circulating hyaluronan concentrations increased to high values after induction of experimental sepsis (from mean baseline values of 242 +/- 26 [SEM] to mean maximum concentrations of 964 +/- 255 micrograms/L [p less than .01]) compared with controls (199 +/- 38 to 303 +/- 32 micrograms/L). A weak negative correlation between mean arterial pressure (MAP) and serum hyaluronan values was found (r2 = .47; p less than .01). Nonsurvivors had higher mean serum hyaluronan concentrations than survivors (603 +/- 147 vs. 285 +/- 43 micrograms/L [p less than .05]). CONCLUSIONS: Experimental sepsis is associated with an increase in serum hyaluronan values. The relationship between decreased MAP and increased serum hyaluronan concentrations could point to reduced liver perfusion as a cause. An association between high hyaluronan values and nonsurvival in sepsis is possible. PMID- 1521447 TI - Fructose-1,6-bisphosphate does not ameliorate hypoxic ischemic injury to the central nervous system in the newborn pig. AB - BACKGROUND AND METHODS: Fructose-1,6-bisphosphate has been shown to improve the outcome of hypoxic ischemic brain injury in adult rabbits. We wished to see if these results could be extended to a newborn animal. Twenty-four 0- to 3-day-old piglets were randomized to receive 300 mg/kg of fructose-1,6-bisphosphate 5 mins before injury, followed by a continuous infusion of 15 mg/kg/min of fructose-1,6 bisphosphate for the next 90 mins, or the equivalent volume of normal saline. Hypoxic ischemic central nervous system damage was induced by ligating both carotid arteries and reducing their BP to two thirds of the normal value for 30 mins. In the last 15 mins of this 30 mins, the FIO2 was reduced to 0.6. At 30 mins, the piglets were resuscitated with an FIO2 of 1.0, the carotid ligatures were released, and the removed blood was reinfused. RESULTS: The neurologic examination scores at 1, 2, and 3 days after injury and pathologic examination scores at 3 days after injury were not different in the fructose-1,6-bisphosphate treated and the control animals. CONCLUSION: Fructose-1,6-bisphosphate does not ameliorate hypoxic ischemic brain injury in the newborn pig. PMID- 1521449 TI - Peripheral and liver tissue oxygen tensions in hemorrhagic shock. AB - BACKGROUND AND METHODS: Hepatic dysfunction after severe hemorrhagic shock is common and may be a consequence of visceral tissue hypoxia. Peripheral tissue PO2 has been suggested to correlate with the development of visceral hypoxia. To test the hypothesis that changes in peripheral tissue PO2 reflect changes in hepatic PO2, we measured subcutaneous PO2, transcutaneous PO2, transconjunctival PO2, and liver tissue PO2, and their relationship with changes in mean arterial blood pressure (MAP) and systemic oxygen transport (DO2), during progressive bleeding in pigs (n = 23). In addition to the tissue PO2, portal vein PO2 and circulating lactate concentrations were also measured in six of the animals. The animals were anesthetized and bled to an MAP of 50 mm Hg within 1 hr. RESULTS: After an induced 10% reduction of MAP, only the DO2 decreased significantly (p less than .05). After a 20% reduction of MAP, the DO2 decreased further and was associated with a significant (p less than .05) reduction of all peripheral tissue PO2 values. A significant (p less than .05) reduction of liver tissue PO2 was observed later during bleeding, after induction of a 30% reduction in MAP. In the subgroup with portal venous PO2 and lactate measurements, reductions of all peripheral tissue PO2 and portal venous PO2 values occurred after a 20% reduction (p less than .05) of MAP. An increase (p less than .05) in the portal venous lactate concentration was observed after a 50% reduction of MAP, and a decrease (p less than .05) in liver tissue PO2 was noted after a 60% reduction of MAP. CONCLUSIONS: Reductions of both peripheral and portal venous PO2 values occur early during hemorrhage. The liver tissue PO2, though initially low, appears to be better defended, suggesting either redistribution of splanchnic blood flow or adaptation in hepatic oxygen demand. PMID- 1521450 TI - Continuous breathing circuit flow and tracheal tube cuff leak: sources of error during pediatric indirect calorimetry. AB - OBJECTIVE: To determine whether continuous gas flow in the breathing circuit or an airleak around the tracheal tube cuff will introduce errors into the measurement of oxygen consumption (VO2) with indirect calorimetry. DESIGN: Nonrandomized, controlled trial. SETTING: Experimental laboratory. SUBJECTS: Ten healthy, anesthetized mongrel dogs, weighing 8 to 12 kg. INTERVENTIONS: Data were recorded at seven levels of flow, from 0 to 12 L/min in excess of minute ventilation, through a continuous breathing circuit. Data were recorded at five levels of tracheal tube cuff leak from 0% to 40% of inspiratory minute volume. MEASUREMENTS AND MAIN RESULTS: VO2 was measured using an indirect calorimeter with constant internal gas flow and calculated from results of blood gas analysis, cooximetry, and thermodilution cardiac output determinations at all levels of continuous breathing circuit flow and cuff leak. BP, heart rate, respiratory rate, arterial and mixed venous blood gases, and body temperature were measured to assess stability of cardiopulmonary function. Continuous breathing circuit flow did not affect the accuracy of indirect calorimetry until the total flow reached a critical value (11.5 L/min) that was slightly below the internal flow constant of the metabolic monitor (12.4 L/min). At higher circuit flows, measured VO2 decreased in a linear fashion, while calculated VO2 remained unchanged. Above the critical flow, the error of indirect calorimetry correlated significantly only with the total circuit flow (r2 = .64), not with the exhaled concentration of CO2 (r2 = .005) or the inspiratory-expiratory oxygen difference (r2 = .004). The continuous flow rate at the critical circuit flow was 66 +/- 15% of the subjects' peak inspiratory flow. Increasing tracheal tube cuff leak produced a progressive decrease in measured VO2 but not in calculated VO2. The difference between measured and calculated VO2 was linearly related to the magnitude of the leak (r2 = .56), and was statistically significantly larger at all levels of cuff leak, when compared with measurements during complete cuff seal. CONCLUSIONS: An indirect calorimeter in which measurement of VO2 is based on internal constant flow rather than spirometry can be used to accurately measure VO2 from a continuous-flow breathing circuit, if the total circuit flow is less than the internal flow. This limitation may restrict the use of continuous flow to a level below the subject's peak inspiratory flow. The accuracy of indirect calorimetry cannot be guaranteed for any amount of tracheal tube cuff leak. PMID- 1521451 TI - Successful resuscitation of a cold water submersion victim with the use of cardiopulmonary bypass. PMID- 1521452 TI - Improvement in cardiac output during airway pressure release ventilation. PMID- 1521453 TI - A further comment on acquired immunodeficiency syndrome and critical care. PMID- 1521454 TI - Superficial cervical plexus block for pulmonary artery catheter insertion. PMID- 1521455 TI - Recollection of intensive care unit admission in the United Kingdom. PMID- 1521456 TI - Methemoglobinemia and pulse oximetry. PMID- 1521457 TI - New use of a central venous pressure catheter with attached subcutaneous cuff. PMID- 1521458 TI - Treatment of gram-negative septic shock with an immunoglobulin. PMID- 1521459 TI - Prolonged postpancuronium paralysis. PMID- 1521460 TI - Aldehyde dehydrogenases and their role in carcinogenesis. AB - Aldehydes are highly reactive molecules that may have a variety of effects on biological systems. They can be generated from a virtually limitless number of endogenous and exogenous sources. Although some aldehyde-mediated effects such as vision are beneficial, many effects are deleterious, including cytotoxicity, mutagenicity, and carcinogenicity. A variety of enzymes have evolved to metabolize aldehydes to less reactive forms. Among the most effective pathways for aldehyde metabolism is their oxidation to carboxylic acids by aldehyde dehydrogenases (ALDHs). ALDHs are a family of NADP-dependent enzymes with common structural and functional features that catalyze the oxidation of a broad spectrum of aliphatic and aromatic aldehydes. Based on primary sequence analysis, three major classes of mammalian ALDHs--1, 2, and 3--have been identified. Classes 1 and 3 contain both constitutively expressed and inducible cytosolic forms. Class 2 consists of constitutive mitochondrial enzymes. Each class appears to oxidize a variety of substrates that may be derived either from endogenous sources such as amino acid, biogenic amine, or lipid metabolism or from exogenous sources, including aldehydes derived from xenobiotic metabolism. Changes in ALDH activity have been observed during experimental liver and urinary bladder carcinogenesis and in a number of human tumors, including some liver, colon, and mammary cancers. Changes in ALDH define at least one population of preneoplastic cells having a high probability of progressing to overt neoplasms. The most common change is the appearance of class 3 ALDH dehydrogenase activity in tumors arising in tissues that normally do not express this form. The changes in enzyme activity occur early in tumorigenesis and are the result of permanent changes in ALDH gene expression. This review discusses several aspects of ALDH expression during carcinogenesis. A brief introduction examines the variety of sources of aldehydes. This is followed by a discussion of the mammalian ALDHs. Because the ALDHs are a relatively understudied family of enzymes, this section presents what is currently known about the general structural and functional properties of the enzymes and the interrelationships of the various forms. The remainder of the review discusses various aspects of the ALDHs in relation to tumorigenesis. The expression of ALDH during experimental carcinogenesis and what is known about the molecular mechanisms underlying those changes are discussed. This is followed by an extended discussion of the potential roles for ALDH in tumorigenesis. The role of ALDH in the metabolism of cyclophosphamidelike chemotherapeutic agents is described. This work suggests that modulation of ALDH activity may an important determinant of the effectiveness of certain chemotherapeutic agents.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1521461 TI - Glutathione transferases and cancer. AB - The glutathione transferases, a family of multifunctional proteins, catalyze the glutathione conjugation reaction with electrophilic compounds biotransformed from xenobiotics, including carcinogens. In preneoplastic cells as well as neoplastic cells, specific molecular forms of glutathione transferase are known to be expressed and have been known to participate in the mechanisms of their resistance to drugs. In this article, following a brief description of recently identified molecular forms, we review new findings regarding the respective molecular forms involved in carcinogenesis and anticancer drug resistance, with particular emphasis on Pi class forms in preneoplastic tissues. The rat Pi class form, GST-P (GST 7-7), is strongly expressed not only in hepatic foci and hepatomas, but also in initiated cells that occur at the very early stages of chemical hepatocarcinogenesis, and is regarded as one of the most reliable markers for preneoplastic lesions in the rat liver. 12-O-Tetradecanoylphorbol-13 acetate (TPA)-responsive element-like sequences have been identified in upstream regions of the GST-P gene, and oncogene products c-jun and c-fos are suggested to activate the gene. The Pi-class forms possess unique enzymatic properties, including broad substrate specificity, glutathione peroxidase activity toward lipid hydroperoxides, low sensitivity to organic anion inhibitors, and high sensitivity to active oxygen species. The possible functions of Pi class glutathione transferases in neoplastic tissues and drug-resistant cells are discussed. PMID- 1521462 TI - A consideration of alternative models for the initiation of translation in eukaryotes. AB - Although recent biochemical and genetic investigations have produced some insights into the mechanism of initiation of translation in eukaryotic cells, two aspects of the initiation process remain controversial. One unsettled issue concerns a variety of functions that have been proposed for mRNA binding proteins, including some initiation factors. The need to distinguish between specific and nonspecific binding of proteins to mRNA is discussed herein. The possibility that certain initiation factors might act as RNA helicases is evaluated along with other ideas about the functions of mRNA- and ATP-binding factors. A second controversial issue concerns the universality of the scanning mechanism for initiation of translation. According to the conventional scanning model, the initial contact between eukaryotic ribosomes and mRNA occurs exclusively at the 5' terminus of the message, which is usually capped. The existence of uncapped mRNAs among a few plant and animal viruses has prompted a vigorous search for other modes of initiation. An "internal initiation" mechanism, first proposed for picornaviruses, has received considerable attention. Although a large body of evidence has been adduced in support of such a mechanism, many of the experiments appear flawed or inconclusive. Some suggestions are given for improving experiments designed to test the internal initiation hypothesis. PMID- 1521463 TI - Aspects in structural studies on ribosomes. PMID- 1521464 TI - Validation and reproducibility of bidirectional laser Doppler velocimetry for the measurement of retinal blood flow. AB - Bidirectional laser Doppler velocimetry (BLDV) for the measurement of retinal blood flow was validated in six anaesthetised minipigs, by comparing BLDV derived results with those obtained using radioactively labelled microspheres (RLM). The mean velocity of blood (Vmean) was calculated from the maximum red blood cell velocity measured by BLDV. Volumetric flow rate was determined from Vmean and vessel diameter, measure from monochromatic fundus photographs. Total retinal blood flow (TRBF) was calculated by summating flow values obtained for each retinal vein draining into the optic disc. A significant correlation was found between the TRBF results obtained by the two techniques (r = 0.99, p less than 0.001). The BLDV results were between 3-35 microliters/min lower than the corresponding RLM results (p = 0.05). Values of 57 +/- 24 microliters/min and 76 +/- 34 microliters/min were obtained for TRBF using the BLDV and RLM techniques respectively. Reproducibility studies with BLDV were also performed in six anaesthetised pigs over three hours and in six normal human volunteers over two hours and two weeks. No significant difference between measurements was found with time. Ninety five percent confidence limits of +/- 9.8% for the six pigs and +/- 8.9% for the six human volunteers were found for measurements on the same day and at two weeks. We conclude that with a sample size of six, changes in flow of approximately 20% can be detected using BLDV and monochromatic fundus photography. PMID- 1521465 TI - Influence of vehicle and anterior chamber protein concentration on cyclosporine penetration through the isolated rabbit cornea. AB - The transcorneal penetration of cyclosporine A has been determined from each of three vehicles across isolated cornea into simulated aqueous humor containing either 50 mg % protein (0.5 mg/ml; as found in a normal eye) or 5000 mg % protein (50 mg/ml; as found in an inflamed eye). Cyclosporine entered the corneal epithelium and stroma/endothelium as well as passed through the cornea from an alpha cyclodextrin vehicle. Entry into the epithelium and stroma/endothelium occurred from an ointment vehicle with limited detectable anterior chamber penetration using 50 mg % protein solution in the anterior chamber. From corn oil vehicle, cyclosporine penetrated across the cornea with a permeability equal to that of alpha cyclodextrin vehicle. The concentration of cyclosporine in both corn oil and ointment vehicles is 8 times greater than that in alpha cyclodextrin vehicle resulting in a flux from corn oil vehicle about 7 or 8 times greater than that seen after alpha cyclodextrin vehicle. The amounts retained in the cornea, however, were relatively low after corn oil compared to cyclodextrin. The penetration of cyclosporine from either the cyclodextrin vehicle or ointment was at least doubled in the presence of 5000 mg % protein in the simulated aqueous humor relative to that seen in 50 mg % protein. This data indicates that the (presumed) absorption and binding of drug by the excess protein in the simulated aqueous humor may have removed free cyclosporine from the solution and sustained a high concentration gradient of free solute across the cornea.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1521466 TI - Oxidation of the N-terminal methionine of lens alpha-A crystallin. AB - Antiserum against the N-terminal peptide of bovine alpha-A crystallin has been used to monitor purification of two different seropositive peptides (i.e. T1a and T1b) from a tryptic digest of bovine lens proteins. Both these peptides have similar amino acid compositions, but peptide T1b has a molecular weight 16 atomic mass units larger than T1a, suggesting posttranslational modification. Analysis of ionization fragments of the T1b peptide by mass spectrometry demonstrates that this difference in molecular weight is due to the in vivo oxidation of the N terminal met residue of the alpha-A crystallin molecule. PMID- 1521467 TI - Induction of experimental autoimmune uveitis with rhodopsin synthetic peptides in Lewis rats. AB - Rhodopsin, a membrane protein of rod photoreceptor cells, induces an experimental autoimmune uveitis (EAU) in Lewis rats. Synthetic peptides derived from rhodopsin sequences that cover hydrophilic, exposed regions of the protein were tested for their capacity of eliciting in vitro T cell proliferation and their ability for inducing EAU in Lewis rats. Rats were injected with rhodopsin's peptides mixed in complete Freund's adjuvant containing M. tuberculosis H37Ra (5 mg/ml) three days after pretreatment with cyclophosphamide (20 mg/kg). ELISA results indicate that all peptides induce antibody responses; however antibody titers differ among sera tested. Immunization with four peptides--the amino-terminus (2-32), loop I-II (61 75), loop V-VI (230-251), and the carboxyl-terminus (324-348 and 331-342) induced both antibody and T cell responses. In all cases, the proliferative responses of cells derived from peptide-injected rats were stronger against the immunizing peptide than against native protein. Three distinct uveitogenic epitopes were identified on rhodopsin's cytoplasmic surface--within the rhodopsin carboxyl terminus (324-348), loop I-II (61-75), and loop V-VI (230-250). Histopathologically, at the immunized doses, total destruction of the photoreceptor cell layer was observed as compared to the control group. Loop V-VI caused severe inflammation of the retina while the other pathogenic peptides produced less severe destruction with few inflammatory cells present. Our study indicates that the major immunodominant T cell epitope (331-342) is also involved in EAU induction but is not the primary uveitogenic site. PMID- 1521468 TI - Two-dimensional gel electrophoretic analysis of human lens proteins. AB - Human lens proteins from clear lenses were separated and identified using two dimensional polyacrylamide electrophoresis. Isoelectric focusing, both equilibrium and non-equilibrium, was performed in the first dimension and SDS electrophoresis in the second dimension. Proteins were identified by Western blotting and sequencing techniques and by comparison with patterns obtained with purified crystallin fractions. Analyses were performed on total urea soluble proteins of lenses varying in age from fetal to 73 yr. Several hundred protein spots representing crystallins, cytoskeletal proteins and enzymes were resolved in the fetal lens. In the older lenses there was a dramatic increase in the number of protein species in the molecular weight range of the crystallins and a reduced number of discrete protein species visible at molecular weights greater than 50,000. Conversely, a number of proteins below approximately 15 kDa were visible even in the fetal lens. The number and amount of polypeptides in this molecular weight range were increased in the older lenses. Many of these low molecular weight species could be assigned to either the alpha-, beta- or gamma crystallin fractions. An age dependent increase in the number of acidic species of both crystallins and other proteins, such as, glyceraldehyde 3-phosphate dehydrogenase was observed as well as the loss or mobility change of gamma crystallin. Two-dimensional gel electrophoresis provides a sensitive and practical technique for characterizing all of the proteins of the human lens. PMID- 1521469 TI - Transforming growth factor-beta modulates effects of epidermal growth factor on corneal epithelial cells. AB - In order to understand the mechanisms that bring about maintenance and restoration of the integrity of corneal epithelium, we investigated independent and combined effects of transforming growth factor-beta (TGF-beta) and epidermal growth factor (EGF) on rabbit corneal epithelial cells in cell and organ culture. Specifically, we determined whether incubation with these factors influenced 1) cellular proliferation, 2) ability of cells to attach to a fibronectin matrix, and 3) the rate of epithelial migration over corneal stroma. Incubation with TGF beta caused a dose-related decrease in the incorporation of 3H-thymidine by the epithelial cells. EGF increased 3H-thymidine incorporation, but this effect was antagonized by the addition of TGF-beta into the incubation medium. Incubation with EGF increased the numbers of cells that attached to a fibronectin matrix. TGF-beta itself did not affect the number of attached cells but, again, it antagonized the stimulatory effect of EGF. Similarly, when corneal blocks were cultured with EGF, epithelial migration increased in a dose-related manner. TGF beta itself did not affect epithelial migration at any of the concentrations tested (0.1-10 ng/ml), but it antagonized EGF-stimulated epithelial migration. These findings suggest that the proliferation and the migration of corneal epithelial cells are regulated by different mechanisms, and that TGF-beta serves as a modulator of the effects of EGF. PMID- 1521470 TI - Immunity and immune privilege elicited by autoantigens expressed on syngeneic neonatal neural retina grafts. AB - Achieving the long-term goal of successful engraftment of retinal tissues into eyes blinded by endogenous retinal failure will depend, at least in part, on controlling the immune response to antigens expressed on retinal grafts. Since histoincompatible tissues will have to be used for such transplants, methods to control immune rejection directed at transplantation alloantigens must be devised. In addition, it has recently been observed in mice that developing neural retinal tissues express retina-specific antigens that have the potential to contribute to graft failure. To examine the potential risk of this contribution, syngeneic neonatal neural retinas were implanted into the anterior chamber, vitreous cavity, and subconjunctival space of adult BALB/c mice. During two weeks post-implantation, the fate of these grafts was observed clinically and histologically, and the retina-specific immune responses of the recipients were evaluated. Whereas grafts placed intraocularly thrived, carried out their inherent developmental potential, and were healthy and intact at the end of the observation interval. Grafts placed extraocularly expressed their differentiation program poorly. These grafts underwent rapid decline and attrition, although the process was not accompanied by significant inflammation. Recipients of subconjunctival, but not AC or VC, implants developed retina-specific delayed hypersensitivity. Alternatively, mice bearing AC and VC implants of neonatal neural retina developed retina-specific anterior chamber associated immune deviation. It is concluded that retinal autoantigens are expressed on developing neural retinal tissues and these antigens are highly immunogenic when retinal grafts are placed at conventional body sites. When similar grafts are placed in immune privileged compartments of the normal eye, they enjoy significant survival. Circumstantial evidence indicates that intraocular retinal grafts are protected and maintained in part by the emergence of systemic retinal auto antigen-specific immune suppression. PMID- 1521471 TI - Localization of vasoactive intestinal peptide (VIP) messenger RNA (mRNA) in amacrine cells of rat retina. AB - We detected vasoactive intestinal peptide (VIP) messenger RNA (mRNA) in the rat retina using an in situ hybridization technique and a 35S-labelled cDNA probe. VIP mRNA was present in the cells of the inner nuclear layer (INL). The VIP mRNA positive cells showed a distribution similar to that of the VIP-like immunoreactive amacrine cells. This observation suggests that VIP mRNA undergoes transcription in the VIP-immunoreactive amacrine cells. PMID- 1521472 TI - Sun protection. PMID- 1521473 TI - Nonoccupational dermatitis to "black" rubber mix: Part II. PMID- 1521474 TI - A dermatologic diary. Portrait of a practice. PMID- 1521475 TI - Widespread Candida folliculitis in a nontoxic patient. AB - We present a case of widespread Candida folliculitis in a nontoxic, immunocompetent woman. Predisposing factors included obesity and use of systemic antibiotics and topical steroids. Diagnosis was made through potassium hydroxide and Gram's stain examination of the pustular contents. The patient was treated with oral ketoconazole and topical econazole, with resolution of the eruption in six weeks. We suggest that temperature played a role in the follicular location of the lesions. PMID- 1521476 TI - Multiple symmetrical lipomatosis. AB - We report a patient with multiple symmetrical lipomatosis, which is an unusual subgroup of lipomatous disease. This entity is described along with a brief review of the literature on this disease and associated disorders. PMID- 1521477 TI - Nodular vasculitis associated with propylthiouracil therapy. AB - Cutaneous vasculitis is a rare complication of propylthiouracil therapy. We describe a patient who presented with lower extremity subcutaneous nodules, hemorrhagic bullae, and necrotic ulcers during treatment with this agent. Examination of a skin biopsy specimen revealed nodular vasculitis. This type of vasculitis has not been described in association with propylthiouracil therapy before. Nodular vasculitis not associated with the drug is characterized by a chronic protracted course, whereas in the patient reported the lesions rapidly regressed when use of the drug was discontinued. PMID- 1521478 TI - Coexistent oral cryptococcosis and Kaposi's sarcoma in acquired immunodeficiency syndrome. AB - As experience with the acquired immunodeficiency syndrome has grown during the last decade, it has become important to recognize interactions between the opportunistic infections and malignancies that complicate the course of patients with acquired immunodeficiency syndrome. Our recent experience as described in this paper reveals that Kaposi's sarcoma and cryptococcal infection can associate in such a manner. The first reported case of oral Cryptococcus neoformans infection within a Kaposi's sarcoma lesion in a patient with acquired immunodeficiency syndrome is described. Based on the clinical course of this patient, it is an important consideration that the sarcoma may have harbored and even protected the fungus during systemic amphotericin B therapy. PMID- 1521479 TI - Acrokeratosis paraneoplastica of Bazex: report of a case in a young black woman. AB - Acrokeratosis paraneoplastica of Bazex is a rare cutaneous syndrome associated with malignant neoplasms of the pulmonary and upper gastrointestinal tract, or cervical metastatic adenopathy, usually seen in middle-aged white men. We present a unique case of Bazex syndrome in that the patient was young, black, and a woman. PMID- 1521480 TI - Cutaneous sarcoidal granulomas in a patient with primary biliary cirrhosis. AB - We report here the case of a fifty-year-old Japanese woman with a history of primary biliary cirrhosis who presented with a sarcoidal granulomatous plaque on the face. Although the occurrence of extra-hepatic granulomas and primary biliary cirrhosis has been documented, this is the first case report of cutaneous sarcoidal granulomas in the absence of demonstrable sarcoidosis occurring in a patient with primary biliary cirrhosis. Because primary biliary cirrhosis and sarcoidosis are systemic granulomatous diseases of unknown cause, the coexistence of findings compatible with both entities has led to speculation that they are related. We provide a brief review of these two diseases to help examine this hypothesis. PMID- 1521481 TI - Fish tank granuloma: report of a case. PMID- 1521482 TI - Pigmentation of the gums following hydroxychloroquine therapy. AB - The authors describe a case of pigmentation of the gums occurring after therapy with hydroxychloroquine. A twenty-eight-year-old woman with discoid lupus erythematosus was treated only with hydroxychloroquine. After seven months of this therapy, a diffuse bluish-gray pigmentation was apparent on the vestibular surface of the gums of both dental arches. No pigmented lesions were noticed on either the skin or the nails. PMID- 1521483 TI - Plaque-type intertriginous cutaneous calcification. AB - Cutaneous calcification is classified into four types: dystrophic, idiopathic, tumoral, and metastatic. We present a patient with systemic lupus erythematosus undergoing hemodialysis who noted large plaque-like cutaneous calcifications in the axillae and groin. Some plaques occurred in association with striae related to prior corticosteroid therapy for the patient's underlying systemic disease. This case is unusual because of the clinical presentation, its demonstration of both dystrophic and metastatic types of calcification, and histologic calcification of elastic fibers simulating pseudoxanthoma elasticum. PMID- 1521484 TI - Hsinchiapo. PMID- 1521485 TI - Drug abuse. PMID- 1521486 TI - Protective value of surgical gloves including the "cut resistant variety". PMID- 1521487 TI - A dermatologic diary. Portrait of a practice. PMID- 1521488 TI - Multiple scattered granulomatous skin lesions in cat scratch disease. AB - We report a patient with cat scratch disease who presented with multiple scattered nodular lesions on the legs. Examination of skin biopsy specimens revealed a granulomatous pattern. In our opinion, this is a previously undescribed secondary cutaneous reaction of cat scratch disease. The pathogenesis of this reaction is unclear but some data suggest that the eruption might be caused by a hematogenous spread of cat scratch disease bacteria to the skin. Pathogenetic relationships with so-called bacillary angiomatosis, recently described in patients with acquired immunodeficiency syndrome, are reviewed here. PMID- 1521489 TI - Scurvy. PMID- 1521490 TI - Pruritus and the parakeet. AB - Pruritus can be due to a variety of factors and can often be difficult for a physician to manage. Often the etiology is psychosomatic, wherein a careful history is the key to proper diagnosis. Such a case is presented. PMID- 1521491 TI - Benign symmetric lipomatosis in a patient with severe scalp psoriasis. AB - Benign symmetric lipomatosis, or Madelung's disease, is a rare condition of undetermined cause characterized by symmetrical subcutaneous masses that consist of normal adipose tissue and are located predominantly in the head and neck areas. A case of benign symmetric lipomatosis in a patient with unusual psoriasis and excessive alcohol intake is presented. PMID- 1521492 TI - Treatment of notalgia paresthetica with capsaicin. AB - Twenty-four patients with notalgia paresthetica were treated with topical capsaicin (Zostrix) in a concentration of 0.025 percent for four months. In approximately 70 percent of the patients who remained in the study, relief of pruritus was achieved up to the 90 percent level. In the majority of these patients pruritus returned when use of the medication was stopped. The history, causes, and prevalence of the condition are reviewed. This treatment is the first described that is relatively effective. PMID- 1521493 TI - Oral lesions in patients with psoriasis: a controlled study. AB - Stomatitis areata migrans was found in 5.4 percent of patients with psoriasis compared to 1 percent of control patients, while benign migratory glossitis was identified in 10.3 percent of patients with psoriasis and 2.5 percent of control patients. The association of these disorders with psoriasis indicates that they may be manifestations of psoriasis of the oral mucosa. PMID- 1521494 TI - Juvenile xanthogranuloma. AB - Juvenile xanthogranuloma is a benign cutaneous growth presenting as papules or nodules. It is characterized by an intradermal collection of lipid-laden macrophages and varying degrees of fibroblastic proliferation. We have recently observed two patients with xanthogranulomas: one was found to have a papular type and the second patient had multiple nodular growths. We present these cases, which should be considered in the differential diagnosis of skin nodules. PMID- 1521495 TI - Flashlamp-pumped pulsed dye laser treatment for pyogenic granuloma. AB - Pyogenic granuloma is a frequently diagnosed, benign vascular lesion common in children and young adults. Treatment of pyogenic granuloma consists of removal of the lesion for therapeutic as well as diagnostic purposes. Current treatment modalities include curettage with electrodesiccation, cryosurgery, chemical cauterization, and argon laser therapy. However, these methods are not without the risk of complications such as scarring and pigmentary changes. The recently reported success of the flashlamp-pumped pulsed dye laser for treating telangiectasias, hemangiomas, and port-wine stains led us to hypothesize that this same device, using different variables, such as multiple overlapping pulses, would be of benefit in the treatment of pyogenic granuloma. We describe three patients with pyogenic granuloma treated with the pulsed dye laser, with the total number of treatments and energy densities varying according to the size of the initial lesion. All three patients demonstrated complete resolution of lesions with no evidence of scarring, atrophy, or pigment changes. This preliminary report suggests that pulsed laser therapy should be considered in the treatment of pyogenic granuloma, especially in cosmetically sensitive areas. PMID- 1521496 TI - Generalized elastophagocytic granuloma. AB - The case of an eighty-three-year-old woman with the sudden onset of a generalized pruritic eruption is reported. The skin lesions resembled disseminated subacute lupus erythematosus on clinical examination, but actinic granuloma or annular elastolytic giant cell granuloma was seen in biopsy specimens of the lesions. Our case was differentiated from generalized granuloma annulare by the distinct zoning of elastolysis and the distribution of giant cells. PMID- 1521497 TI - Enhanced services and stipends for foster parents: effects on retention rates and outcomes for children. AB - Current national trends show that although the number of available foster homes is shrinking, the number of children and adolescents being cared for in the family foster care system is growing. This study demonstrates the significant benefits to both foster parents and the children in their care of providing enhanced services and stipends to foster parents. PMID- 1521498 TI - A survey of the first hundred volumes of chromosoma. PMID- 1521499 TI - Amphibian oocytes and sphere organelles: are the U snRNA genes amplified? AB - The sphere organelles (spheres) of Xenopus and other amphibian oocytes are known to contain small nuclear ribonucleoprotein particles (snRNPs) and have been suggested to play a role in snRNP complex assembly. Coupled with the similarities that exist between spheres and nucleoli and the quantitative and kinetic aspects of snRNA synthesis in the Xenopus oocyte, we have investigated whether or not the U snRNA encoding genes are amplified in Xenopus oogenesis, the spheres being possible sites for the location of such extrachromosomal gene copies. By applying a number of quantitative nucleic acid hybridization procedures to both total and fractionated oocyte and somatic DNA, employing both homologous and heterologous U snRNA gene probes and suitable amplification and non-amplification control probes, we show that the U snRNA genes do not undergo any major amplification in Xenopus oogenesis. Therefore, the analogy between the sphere organelles and nucleoli appears to be limited. The role of the spheres and their relationship to other snRNP containing structures, specifically B snurposomes, and the sphere organizer loci remains obscure. PMID- 1521500 TI - Cell cycle dependent chromosomal movement in pre-mitotic human T-lymphocyte nuclei. AB - Fluorescent in situ hybridization with chromosome specific probes was used in conjunction with laser scanning confocal microscopy to assess the three dimensional distribution of chromosomes in human T-lymphocyte nuclei. Cells in the G1-phase of the cell cycle exhibit a distinctly non-random chromosome organization:centromeric regions of the ten chromosomes examined are localized on the nuclear periphery, often making contact with the nuclear membrane, while telomeric domains are consistently localized within the interior 50% of the nuclear volume. Chromosome homolog pairing is not observed. Transition from the G1 to G2 cell cycle phase is accompanied by extensive chromosome movement, with centromeres assuming a more interior location. Chromosome condensation and chromatin depleted areas are observed in a small subset of G2 nuclei approaching mitosis. These results demonstrate that dynamic chromosome rearrangements occur in non-mitotic nuclei during the cell cycle. PMID- 1521501 TI - The gene structure of Xenopus nuclear lamin A: a model for the evolution of A type from B-type lamins by exon shuffling. AB - Nuclear lamins are intermediate filament (IF) type proteins that form a fibrillar network underlying the inner nuclear membrane. The existence of multiple subtypes of lamins in vertebrates has been interpreted in terms of functional specialization during cell division and differentiation. The structure of a gene encoding an A-type lamin of Xenopus laevis was analysed. Comparison with that of a B-type lamin of the same species shows remarkable conservation of the exon/intron pattern. In both genes the last exon, only 9-12 amino acids in length, encodes the complete information necessary for membrane targeting of lamins, i.e. a ras-related CaaX motif. The lamin A specific extension of the tail domain is encoded by a single additional exon. The 5' boundary of this exon coincides with the sequence divergence between human lamins A and C, for which an alternative splice mechanism had previously been suggested. Arguments are presented suggesting that B-type lamins represent the ancestral type of lamins and that A-type lamins derived there from by exon shuffling. The acquisition of the new exon might explain the different fates of A- and B-types lamins during cell division. PMID- 1521502 TI - Caffeine demethylase activity in human and Dark Agouti rat liver microsomes. Comparison with aminopyrine N-demethylase activity. AB - Human and Dark Agouti rat liver microsomes were analyzed for caffeine metabolism focusing on demethylase activity by using a simplified isocratic HPLC method. Results showed that, despite interspecies quantitative and qualitative differences on caffeine metabolism, mainly demethylated caffeine metabolites were detected in both species. Humans showed interindividual quantitative differences in caffeine demethylase activity in contrast to rats and, in both cases, the proportion of metabolites remained constant. In addition, aminopyrine N demethylase activity was assayed, showing a direct correlation with caffeine demethylase activity in humans (r = 0.71) that is reported here for the first time, but not in rats (r = 0.21). These results indicate that, in human liver microsomes, caffeine and aminopyrine could be demethylated by the same or by closely related enzymes; whereas in Dark Agouti rats, there is no apparent relation between caffeine and aminopyrine demethylation pathways. PMID- 1521504 TI - Managing heart failure--home or hospital? PMID- 1521503 TI - Hydrolysis of the 2',3'-allylic epoxides of allylbenzene, estragole, eugenol, and safrole by both microsomal and cytosolic epoxide hydrolases. AB - 2',3'-Allylic epoxide derivatives of allylbenzene and its analogs estragole, eugenol, and safrole were synthesized, and their enzymatic conversion to dihydrodiols by cytosolic and microsomal epoxide hydrolases was examined. All four epoxides were good substrates for both epoxide hydrolases, with Michaelis constants in the low micromolar range. Two putatively selective inhibitors of cytosolic and microsomal epoxide hydrolases, trichloropropylene oxide and nordihydroguaiaretic acid, were used to inhibit the hydrolysis of these allylic epoxides. Minimal selectivity toward either hydrolase was seen with either inhibitor, suggesting that the "selectivity" of these inhibitors is highly substrate-dependent. The susceptibilities of these epoxides to rapid hydrolysis by both epoxide hydrolases may explain their low genotoxic potencies in vivo. PMID- 1521505 TI - Prognosis of luxated non-vital maxillary incisors treated with calcium hydroxide and filled with gutta-percha. A retrospective clinical study. AB - A material of 885 luxated, non-vital incisors was evaluated radiographically with respect to healing of periodontal tissues including inflammatory root resorption and occurrence of ankylosis and cervical root fractures. The results were assessed after completion of calcium hydroxide treatment and 4 years after filling of the root canal with gutta-percha. After treatment with calcium hydroxide, periapical healing occurred in 95% of the teeth. Four years after filling with gutta-percha, periapical healing was present in 91% of the teeth. In the remaining teeth, recurrent or persistent periapical radiolucency was more frequent in overfilled than adequately filled teeth (P = 0.0001). There was no difference between immature and mature teeth. Inflammatory root resorption healed in 192 of 197 teeth (97%); in 5 teeth it developed into ankylosis. Ankylosis occurred in 13 teeth, all of which were intruded into the alveolar bone at the time of injury. The frequency of cervical root fractures was markedly higher in immature than mature teeth (P greater than 0.0001). Among immature teeth, the frequency of fractures was dependent on the stage of root development (chi 2 = 31.6) and ranged from 77% in teeth with the least to 28% in teeth with the most developed roots. The frequency of fractures was also related to the defects after healing of inflammatory root resorption in the cervical area of the root, significant at P less than 0.0001. PMID- 1521506 TI - Induced periapical lesions in ferret canines: histologic and radiographic evaluation. AB - Ferrets have been utilized in endodontic research to study periapical responses. However, various aspects of induction and healing of periapical pathosis in ferrets are unclear. This study evaluated the radiographic and histopathologic features of induced periapical lesions. Periapical pathosis was consistently produced in 8 canines of 2 ferrets by extirpating the pulp, leaving the cavities open for a week, then sealing for 12 weeks. The resulting lesions were evaluated radiographically every two weeks. The animals were then killed and the induced lesions evaluated histologically and histobacteriologically. Four untreated canines from 2 other ferrets were used as controls. Results showed that periapical rarefactions were visible in all teeth in the experimental group within 4 weeks. Histologically, the induced lesions consisted principally of a mononuclear inflammatory infiltrate, dominated by macrophages but with numerous lymphocytes. With Brown & Brenn staining, bacteria were demonstrated in the pulp space of teeth in which the lesions were induced and in the apical arborization of the canal system. Only one specimen had bacteria within the periapical lesion. PMID- 1521507 TI - Sealing ability of sectional injection thermoplasticized gutta-percha technique with varying distance between needle tip and apical foramen. AB - The purpose of this investigation was to evaluate the influence of the distance of the needle tip from the apical foramen on the apical seal and the length control of the root filling material when thermoplasticized gutta-percha is injected using a sectional injection technique. Ninety-nine human single-rooted mandibular incisors and permanent premolars with straight canals were divided into three equal Groups A, B and C. In Group A the teeth had relatively the wider root canal, in Group C the narrowest, while in Group B root canal size was intermediate. The root canals of all teeth were prepared with a step-back technique. Roots of Group A were instrumented to a Size 70 4 mm short of the working length, while roots of Groups B and C to a Size 70 6 mm and 8 mm short of the working length, respectively. The teeth of all groups were covered with aluminium foil and embedded in acrylic blocks. After the placement of sealer (Roth 811) the root canals of all teeth were obturated with injection-molded thermoplasticized gutta-percha using a three-stage sectional technique. The roots remained in India ink for three days and then cleared by successive immersion in nitric acid, ascending grades of alcohol and finally in xylene. The linear dye penetration and the linear apical underextentionion of the root canal filling were measured by two independent examiners under a stereo microscope. There was no significant difference in the linear dye leakage between the groups.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1521509 TI - Acromegaly. PMID- 1521508 TI - Physiology of growth hormone secretion and action. AB - Growth hormone secretion by the pituitary gland is dependent on the dual regulation exerted by growth hormone-releasing hormone and somatostatin, which are the final integrative pathways for several signals reaching the hypothalamus. Regulatory signals include neurotransmitters, neuropeptides, and peripheral signals such as hormones or nutrients. In the circulation, growth hormone is bound to specific binding proteins and, by activating specific receptors, exerts a variety of peripheral actions. PMID- 1521510 TI - Clinical actions of growth hormone. AB - Although biotechnology has provided physicians with essentially unlimited supplies of growth hormone (GH), there are currently only a few clear-cut indications for exogenous GH therapy. Data now support the use of GH in the treatment of children with GH deficiency and short girls with Turner syndrome. Tantalizing preliminary data suggest that GH therapy has a role in the management of short, poorly growing children with other causes for their growth failure. Recent studies have examined the utility of GH therapy in GH-deficient adults, whereas other studies suggest that GH improves the clinical status of GH sufficient older adults. This article explores the recent data underlying these claims. PMID- 1521511 TI - Etiology of pituitary acromegaly. AB - Pituitary tumors secreting growth hormone are clonal neoplasms that may arise following a somatic mutation within the somatotroph cell. Promotion of tumor growth also appears to be regulated by hypothalamic growth hormone-releasing hormone, which exerts a trophic action on the pituitary cell. Unraveling the mechanisms of pituitary tumorigenesis will facilitate the application of novel therapeutic techniques, genetic screening, and follow-up of tumor responses. PMID- 1521512 TI - Pituitary pathology in acromegaly. AB - This review summarizes the morphologic findings in patients with acromegaly correlated with data on hormone secretion and regulation in vivo and in vitro. The importance of careful morphologic analysis that allows recognition of the varied diseases that have similar manifestations is emphasized. The gaps in our knowledge of pathogenesis are glaring, but continued dedication to the investigation of structure-function correlations combined with a greater understanding of the molecular basis of disease will, no doubt, lead to new discoveries and elucidate the factors underlying pituitary tumorigenesis. PMID- 1521513 TI - Ectopic acromegaly. AB - Ectopic acromegaly is a rare syndrome (less than 1% of acromegalic patients) caused by ectopic growth hormone-releasing hormone (GHRH) or growth hormone (GH) producing tumors. Its recognition is clinically important because acromegaly may be a symptom of an aggressive tumor, and different therapeutic approaches are required. Most cases are caused by either extra- or intracranial GHRH-producing tumors, whereas in rare instances the underlying disease is an ectopic GH secreting tumor. The routine evaluation of circulating GHRH in all acromegalic patients may allow its early recognition, because plasma levels greater than 0.3 ng/mL are virtually diagnostic of a GHRH-producing tumor (frequently a bronchial or pancreatic carcinoid), whereas suppressed levels may suggest an ectopic GH producing tumor. In addition to classic imaging techniques, whole body scintiscan with labeled octreotide may help in the localization of ectopic tumors. Surgical removal of the ectopic tumor is the therapy of choice, but it is not always feasible because patients often present with widespread metastases. Patients with GHRH-induced acromegaly benefit from the administration of the long-acting somatostatin analog, octreotide, which reduces GH, IGF-I, and GHRH, and may shrink the ectopic tumor, its metastases, and the secondary pituitary enlargement. PMID- 1521514 TI - Clinical manifestations of acromegaly. AB - Acromegaly is an uncommon disorder and may present in a variety of ways, leading to considerable delay in diagnosis. Unlike other pituitary tumors, tumors associated with acromegaly tend to be fairly large in most patients. Thus, symptoms may be commonly due to the tumor mass as well as to hormone oversecretion. Mortality is two- to threefold increased due to cardiovascular, respiratory, and neoplastic causes. An increase in diabetes mellitus and hypertension may contribute to the first of these. Early treatment may reverse the diabetes, soft tissue changes, sleep apnea, cardiovascular disease, and neuromuscular disease. The effect of early treatment on neoplasia is unclear, and patients probably should continue to be screened, especially for colon neoplasia, even after appropriate therapy for the acromegaly. Hypopituitarism may be present initially as a result of tumor mass but may also develop as a result of ablative therapy. PMID- 1521515 TI - Rheumatologic and skeletal changes in acromegaly. AB - The anabolic functions of growth hormone (GH) and insulin-like growth factor-I (IGF-I) in cartilage and bone metabolism are important in the normal physiology of these tissues. The effects of chronic elevation of GH and IGF-I levels on bony structures produce the typical physical changes associated with acromegaly, whereas the effects on cartilage result in arthropathy, which is usually degenerative. This article presents an overview of the physiologic roles of GH and IGF-I in cartilage and bone metabolism, the clinical features of the degenerative arthropathy and other rheumatologic syndromes associated with acromegaly, effects of acromegaly on bone and mineral metabolism, and an unusual bone disease that is occasionally associated with acromegaly, the McCune-Albright syndrome. PMID- 1521516 TI - Pituitary gigantism. AB - Pituitary gigantism is a rare condition whose association with McCune-Albright syndrome suggests that mutations in alpha-subunit of a Gs protein are an important cause of this condition. In addition to somatotroph adenoma, it is now recognized that somatotroph hyperplasia can also result from increased levels of growth hormone-releasing hormone. Transgenic rats with hypersomatotrophism are prone to renal and hepatic pathology. PMID- 1521517 TI - Diagnosis and endocrine testing in acromegaly. AB - Acromegaly is a characteristic clinical syndrome resulting from excessive production of GH and SmC/IGF-I generally from a GH-producing pituitary tumor. Once the diagnosis is suspected on clinical grounds, it should be established based on persistent elevation of the basal GH, along with an increased SmC/IGF-I level; it is confirmed by a lack of suppressibility of GH levels following a glucose load. Other tests, including the paradoxic GH elevation in response to TRH and LHRH, are helpful in establishing the diagnosis, as well as determining and monitoring the outcome of surgical and medical therapy. The past few years have been enriched with new knowledge in the area of IGF-binding proteins. Evidence of clinical correlation exists regarding GH status, IGF-I levels, and the IGFBPs particularly IGFBP-1 and IGFBP-3. The value of IGFBPs in clinical practice as a diagnostic tool in disorders of GH secretion appears promising, but further studies are required. PMID- 1521518 TI - Surgical management of acromegaly. AB - Surgery is generally the primary therapy of choice in acromegaly, and the predominantly used transsphenoidal approach has proved to be efficient and safe. Surgical results are dependent on preoperative tumor size and extension and preoperative growth hormone levels. Invasion appears to be the most important factor in predicting surgical outcome. Growth hormone levels can be normalized in 71% of all cases and in more than 80% of microadenomas. Persistent growth hormone excess may require reoperation, radiotherapy, or medical treatment. With close interdisciplinary cooperation of neurosurgeons, endocrinologists, and radiotherapists, nearly all acromegalic patients can be successfully treated today. PMID- 1521519 TI - Radiation therapy of acromegaly. AB - Conventional megavoltage irradiation of GH-secreting tumors has predictable effects on tumor mass, GH, and pituitary function. 1. Further growth of the tumor is prevented in more than 99% of patients, with only a fraction of a percent of patients requiring subsequent surgery for tumor mass effects. 2. GH falls predictably with time. By 2 years GH falls by about 50% from the baseline level, and by 5 years by about 75% from the baseline level. The initial GH elevation and the size and erosive features of the sella turcica do not affect the percent decrease in GH from the baseline elevation. 3. With prolonged follow-up, further decrease in GH is seen at 10 and 15 years, with the fraction of surviving patients achieving GH levels less than 5 ng/mL approaching 90% after 15 years in our experience. Gender, previous surgery, and hyperprolactinemia do not seem to affect the response to treatment. Patients with initial GH greater than 100 ng/mL are significantly less likely to achieve GH values less than 5 ng/mL during long term follow-up. 4. Hypopituitarism is a predictable outcome of treatment, is delayed, and may be more likely in patients who have had surgery prior to irradiation. There is no evidence that this complication is more common in patients with acromegaly than in patients with other pituitary adenomas receiving similar treatment. 5. Vision loss due to megavoltage irradiation--using modern techniques and limiting the total dose to 4680 rad given in 25 fractions over 35 days, with individual fractions not exceeding 180 rad--is extremely rare. The reported cases have occurred almost entirely in patients who have received larger doses or higher fractional doses. The theory that patients with acromegaly are prone to radiation-induced injury to the CNS and optic nerves and chiasm because of small vessel disease is not supported by a review of the reported cases. 6. Brain necrosis and secondary neoplasms induced by irradiation are extremely rare. 7. Although anecdotal evidence raises the question of changes in intellectual function following irradiation, this has not been studied in adults receiving pituitary irradiation. PMID- 1521520 TI - Living with acromegaly. AB - Acromegaly is an unusual insidious but potentially serious chronic pituitary disorder. The delay in diagnosis results not only in unique somatic disfigurement but is also associated with significant mental and emotional dysfunction. This article reviews and describes some of these nonclassic and often overlooked features of acromegaly. Particular emphasis is placed on presenting the patients' perspectives of the condition. The author offers some suggestions on the care and counseling of the acromegalic patient. PMID- 1521521 TI - Concepts and strategies for human gene therapy. AB - Methods of modern molecular genetics have been developed that allow stable transfer and expression of foreign DNA sequences in human and other mammalian somatic cells. It is therefore no surprise that the methods have been applied in attempts to complement genetic defects and correct disease phenotypes. Two decades of research have now led to the first clinically applicable attempts to introduce genetically modified cells into human beings to cure diseases caused at least partially by genetic defects. We discuss here some of the strategies being followed for both in vitro and in vivo application of therapeutic gene transfer and summarize some of the technical and conceptual difficulties associated with somatic-cell gene therapy. PMID- 1521522 TI - Regulation of expression of a Xenopus borealis embryonic/larval alpha 3 skeletal actin gene. AB - We have isolated a genomic clone, related in sequence to the skeletal-actin gene sub-family. It is expressed in the skeletal muscle of embryos from the neurula stage onwards and in tadpoles, but not in adults. The equivalent Xenopus laevis gene is expressed as a major transcript in adult muscle, as well as at earlier stages. The intron/exon structure is typical of vertebrate skeletal-actin genes, as is the possession of multiple copies of three serum-response elements in the promoter of this gene. The Xenopus actin and beta-globin genes were fused in their second introns. This construct, which contained 2.4 kb of upstream sequence, was injected into fertilized eggs at the two-cell stage. It showed the normal pattern of tissue-specific transcription. Thus all of the information necessary for appropriate expression of this actin gene in the embryo is contained in the region that extends from a point 2.4 kb upstream of transcription initiation to the centre of the second exon. A series of enhancer constructs were made in which upstream regions of the actin gene were placed upstream of a X. laevis beta-globin gene. The region immediately adjacent to the promoter, containing the three serum-response elements, was able to drive muscle specific expression, and there was also a general enhancement of transcription by regions further upstream. PMID- 1521523 TI - Site-directed mutagenesis of elongation factor Tu. The functional and structural role of residue Cys81. AB - A Cys residue located in the second consensus sequence element (DCPG) of the GTP binding region is highly conserved in bacterial elongation factors (EF) Tu. Chemical modification of this Cys81 in EF-Tu from Escherichia coli by N-tosyl-L phenylalanine chloromethane [Jonak, J., Petersen, T. E., Clark, B. F. C. & Rychlik, I. (1982) FEBS Lett. 150, 485-488], and of homologous Cys residues in other bacterial EF-Tu, selectively blocks the binding of Xaa-tRNA. We have substituted Cys81 with Gly using site-directed mutagenesis of the EF-Tu-encoding tuf A gene. This substitution induces a partial inhibition (20-70%) of: (a) poly(U)-directed poly(Phe) synthesis; (b) EF-Tu/Xaa-tRNA interaction, determined as protection by EF-Tu of the non-enzymic deacylation of Xaa-tRNA; (c) EF-Tu dependent binding of Xaa-tRNA to the mRNA/ribosome complex and (d) the intrinsic GTPase reaction, that is also less sensitive to stimulation by Xaa-tRNA. Our results thus provide evidence that Cys81, though important, is not essential for the binding of Xaa-tRNA to EF-Tu. The accuracy in poly(Phe) synthesis, measured as misincorporation of Leu, was increased. Both the binding affinity of [C81G]EF Tu for the nucleotide and the resistance against thermal denaturation are more strongly decreased in the case of the GDP-bound state than in the case of the GTP bound state, suggesting that Cys81 plays a more specific role in the former conformation. The sensitivity to N-tosyl-L-phenylalanine chloromethane is decreased by 80% but not totally lost. The inhibition by N-tosyl-L-phenylalanine chloromethane treatment of the function of EF-Tu appears to be a consequence of steric hindrance and/or of an altered conformation of EF-Tu.GTP. The lower activities of [C81G]EF-Tu are probably due to long-range effects, mediated by an overall destabilization of the molecule that is particularly pronounced for the GDP-bound state. PMID- 1521524 TI - Characterization and expression of a NADP-malic enzyme cDNA induced by salt stress from the facultative crassulacean acid metabolism plant, Mesembryanthemum crystallinum. AB - The facultative halophyte and crassulacean acid-metabolism plant, Mesembryanthemum crystallium shifts from C3 photosynthesis to crassulacean acid metabolism when exposed to high-salt or drought conditions. To study the molecular basis of this metabolic transition, the expression of NADP(+)-dependent malic enzyme (NADP-ME), which catalyzes the decarboxylation of malate to release pyruvate and CO2, has been investigated. The complete nucleotide sequence of a full-length cDNA clone was determined and found to contain a single open reading frame encoding a 585-amino-acid polypeptide of 64284 Da. The ice plant (M. crystallinum) NADP-ME shares amino acid identities in the range 72.5-79.0% when compared to other higher-plant enzymes and is more closely related to C3 rather than C4 forms of the enzyme. Genomic Southern-blot analysis of ice-plant DNA indicates that NADP-ME is encoded by a small gene family. Steady-state transcript levels increase 8-10-fold in response to salt stress in the leaves. Transcript levels in roots are extremely low and are unaffected by salt-stress treatment. Nuclear run-on experiments, using isolated nuclei from leaf tissue, confirm that the accumulation of NADP-ME transcripts is, in part, the result of increased transcription of this gene during salt stress. PMID- 1521525 TI - A missense mutation Pro157 Arg in lipoprotein lipase (LPLNijmegen) resulting in loss of catalytic activity. AB - Here we report on the molecular defect that leads to a deficiency of lipoprotein lipase (LPL) activity in a proband of Dutch descent. Southern-blot analysis of the LPL gene from the patient did not reveal any major DNA rearrangements. Sequencing of polymerase-chain-reaction-amplified DNA revealed that the proband is a homozygote for G725C, resulting in a substitution of Pro157 for Arg. This substitution alters a restriction site for PvuII, which allowed rapid identification of the mutant allele in family members. Site-directed mutagenesis and transient expression of the mutant LPL in COS cells produced an enzymatically inactive protein, establishing the functional significance of this mutation. This naturally occurring mutation which alters the Pro157 adjacent to Asp156 of the proposed catalytic triad, indicates that this region of the protein is indeed crucial for LPL catalytic activity. PMID- 1521526 TI - Crystal structure of carboxypeptidase T from Thermoactinomyces vulgaris. AB - The crystal structure of carboxypeptidase T from Thermoactinomyces vulgaris has been determined at 0.235-nm resolution by X-ray diffraction. Carboxypeptidase T is a remote homologue of mammalian Zn-carboxypeptidases. In spite of the low degree of amino acid sequence identity, the three-dimensional structure of carboxypeptidase T is very similar to that of pancreatic carboxypeptidases A and B. The core of the protein molecule is formed by an eight-stranded mixed beta sheet. The active site is located at the C-edge of the central (parallel) part of the beta sheet. The structural organization of the active centre appears to be essentially the same in the three carboxypeptidases. Amino acid residues directly involved in catalysis and binding of the C-terminal carboxyl of a substrate are strictly conserved. This suggests that the catalytic mechanism proposed for the pancreatic enzymes is applicable to carboxypeptidase T and to the whole family of Zn-carboxypeptidases. Comparison of the amino acid replacements at the primary specificity pocket of carboxypeptidases A, B and T provides an explanation of the unusual 'A+B' type of specificity of carboxypeptidase T. Four calcium-binding sites localized in the crystal structure of carboxypeptidase T could account for the high thermostability of the protein. PMID- 1521527 TI - Temperature effects on the MgATP-induced electron transfer between the nitrogenase proteins from Azotobacter vinelandii. AB - The temperature dependence of the pre-steady-state MgATP-dependent electron transfer from the MoFe protein to the Fe protein of the nitrogenase from Azotobacter vinelandii has been investigated between 6 degrees C and 31 degrees C by stopped-flow spectrophotometry. Below 14 degrees C, the data are consistent with a model in which interaction of MgATP with nitrogenase is fast and irreversible, and is followed by reversible electron transfer. From the extent and from the rate of the absorbance change, the rate constants for electron transfer from Fe protein to MoFe protein and of the reverse reaction were calculated. The direct rate constant increases with temperature (6-14 degrees C) from about 1 s-1 to about 26 s-1. The rate constant for the reverse reaction was found to be approximately 4 s-1 and invariant with the reaction temperature. Analysis of the data obtained in the temperature range between 6 degrees C and 12 degrees C within the framework of the transition-state theory show that electron transfer from the Fe protein to the MoFe protein occurs via a highly disordered transition state with activation parameters delta H(0) ++ = 289 kJ.mol-1 and delta S(0) ++ = 792 J.K-1.mol-1. The Eyring plot of the stopped-flow data displays an inflection point around 14 degrees C. From the stopped-flow data obtained between 18 degrees and 27 degrees C the activation parameters delta H(0) ++ and delta S(0) ++ for the reduction of the MoFe protein by Fe protein are calculated to be 90 kJ.mol-1 and 99 J.K-1.mol-1 respectively. A second inflection point in the Eyring plot could exist around 28 degrees C. PMID- 1521528 TI - Intermediates of peroxisomal beta-oxidation of [U-14C]hexadecanedionoate. A study of the acyl-CoA esters which accumulate during peroxisomal beta-oxidation of [U 14C]hexadecanedionate and [U-14C]hexadecanedionoyl-mono-CoA. AB - 1. The oxidation of [U-14C]hexadecanedionoyl-mono-CoA was stimulated by CoA, by carnitine in the absence of CoA and by the presence of an NAD(+)-regenerating system. 2. Substrate inhibition was observed with respect to [U 14C]hexadecanedionoyl-mono-CoA at concentrations greater than 35 microM. 3. Acetyl-CoA and the dicarboxyl-CoA esters of chain length C6-16 were detected by HPLC under standard incubation conditions. 4. In the absence of the NAD(+) regenerating system, 2-enoyl-CoA and 3-hydroxacyl-CoA esters were detected. 5. In general, the peroxisomal beta-oxidation of dicarboxylates is very similar to that of monocarboxylates [Bartlett, K., Hovik, R., Eaton, S., Watmough, N. J. & Osmundsen, H. (1990) Biochem. J. 270, 175-180] except that chain shortening does not proceed beyond C6. 6. We conclude that the peroxisomal beta-oxidation of dicarboxylates is regulated by the redox state of the peroxisomal matrix and CoA availability. PMID- 1521529 TI - Lipid vesicles which can bind to protein kinase C and activate the enzyme in the presence of EGTA. AB - Maximal protein kinase C activity with vesicles of phosphatidic acid and 1,2 dioleoyl-sn-glycerol is observed in the absence of added Ca2+. Addition of phosphatidylcholine to these vesicles restores some calcium dependence of enzyme activity. 1,2-Dioleoyl-sn-glycerol eliminates the Ca(2+)-dependence of protein kinase C activity found with phosphatidic acid alone. Phorbol esters do not mimic the action of 1,2-dioleoyl-sn-glycerol in this respect. This suggests that the 1,2-dioleoyl-sn-glycerol effect is a result of changes it causes in the physical properties of the membrane rather than to specific binding to the enzyme. The effect of 1,2-dioleoyl-sn-glycerol on the phosphatidic-acid-stimulated protein kinase C activity is dependent on the molar fraction of 1,2-dioleoyl-sn-glycerol used and results in a gradual shift from Ca2+ stimulation at low 1,2-dioleoyl-sn glycerol concentrations to calcium inhibition at higher concentrations of 1,2 dioleoyl-sn-glycerol. Phosphatidylserine-stimulated activity is also shown to be largely independent of the calcium concentration at higher molar fractions of 1,2 dioleoyl-sn-glycerol. Thus, with certain lipid compositions, protein kinase C activity becomes independent of the calcium concentration or requires only very low, stoichiometric binding of Ca2+ to high affinity sites on the enzyme. Protein kinase C can bind to phosphatidic acid vesicles more readily than it can bind to phosphatidylserine vesicles in the absence of calcium. Addition of 1,2-dioleoyl sn-glycerol to phosphatidylserine vesicles promotes the partitioning of protein kinase C into the membrane in the absence of added Ca2+. There is no isozyme specificity in this binding. These results suggest that a less-tightly packed headgroup region of the bilayer causes increased insertion of protein kinase C into the membrane. This is a necessary but not sufficient condition for activation of the enzyme in the presence of EGTA. PMID- 1521530 TI - Biosynthesis and intracellular transport of alpha-2,6-sialyltransferase in rat hepatoma cells. AB - We investigated biosynthesis, intracellular transport and release of beta galactoside alpha-2,6-sialyltransferase in a dexamethasone-inducible rat hepatoma cell line. Confluent cells were induced by 10 microM dexamethasone for 24 h, and metabolically labelled with [35S]methionine/cysteine, followed by immunoprecipitation of sialyltransferase and electrophoretic/fluorographic analysis. The 35S-labelled enzyme was synthesized as a 46-kDa precursor, converted to an intermediate 47-kDa form after 1 h, and gradually to a mature form of 48 kDa within the following 3 h. By means of either tunicamycin inhibition of N-glycosylation or cleavage of N-glycans from isolated sialyltransferase using N-glycosidase F, the sizes of the precursor and the mature form were reduced to 41 kDa and 43 kDa, respectively. After a 4-h chase, treatment with endoglycosidase H revealed two distinct molecular forms of sialyltransferase, bearing either two N-acetyllactosamine-type or one oligomannose-type and one N-acetyllactosamine-type N-linked sugar chain. In addition, sialyltransferase became sensitive to neuraminidase digestion after a 4 h chase. The half-life of intracellular [35S]sialyltransferase was estimated at 3 h. A soluble form was detectable in the supernatant, 2 h after the pulse. Only 12% of the initially labelled sialyltransferase was found in the medium after 12 h, while 73% of the enzyme was degraded intracellularly. To characterize a possible intracellular degradation site, we studied intracellular transport in the presence of either secretion-blocking or acidotropic agents or protease inhibitors. Degradation was significantly delayed by all treatments. Our results show that sialyltransferase follows the secretory pathway as a membrane protein and is retained at a late Golgi stage. We suggest that the bulk of sialyltransferase in rat hepatoma cells is diverted to a post-Golgi degradation pathway. This route contrasts with the post-Golgi trafficking of beta-1,4 galactosyltransferase in HeLa cells, which is constitutively secreted [Strous, G. J. A. M. & Berger, E. G. (1982) J. Biol. Chem. 257, 7623-7628]. PMID- 1521531 TI - Protein structure of pig liver 4-aminobutyrate aminotransferase and comparison with a cDNA-deduced sequence. AB - The amino acid sequence of pig liver 4-aminobutyrate aminotransferase has been determined by gas-phase sequencing of proteolytically derived peptide fragments. The sequence differs substantially from that predicted for the same enzyme on the basis of the sequence of cDNA derived from pig brain in recently published work [Kwon, O., Park, J. & Churchich, J. E. (1992) J. Biol. Chem. 267, 7215-7216]. Apart from a few minor differences, the two sequences are completely different in the segment of protein comprising the 36 residues at positions 107-142. Insertion of a cytosine between bases 402 and 403 in the cDNA sequence, together with deletion of the guanine at position 510, results in a DNA sequence which predicts exactly the amino acid sequence determined by peptide analysis in the present work. The mammalian enzyme has approximately 44% sequence identity with the same enzyme from two unicellular eukaryotes (Saccharomyces cerevisiae, Aspergillus nidulans) and 22% identity with that from Escherichia coli. PMID- 1521532 TI - Basement-membrane heparan sulfate proteoglycan binds to laminin by its heparan sulfate chains and to nidogen by sites in the protein core. AB - A large, low-density form of heparan sulfate proteoglycan was isolated from the Engelbreth-Holm-Swarm (EHS) tumor and demonstrated to bind in immobilized-ligand assays to laminin fragment E3, collagen type IV, fibronectin and nidogen. The first three ligands mainly recognize the heparan sulfate chains, as shown by inhibition with heparin and heparan sulfate and by the failure to bind to the proteoglycan protein core. Nidogen, obtained from the EHS tumor or in recombinant form, binds exclusively to the protein core in a heparin-insensitive manner. Studies with other laminin fragments indicate that the fragment E3 possesses a unique binding site of laminin for the proteoglycan. A major binding site of nidogen was localized to its central globular domain G2 by using overlapping fragments. This allows for the formation of ternary complexes between laminin, nidogen and proteoglycan, suggesting a key role for nidogen in basement-membrane assembly. Evidence is provided for a second proteoglycan-binding site in the C terminal globule G3 of nidogen, but this interaction prevents the formation of such ternary complexes. Therefore, the G3-mediated nidogen binding to laminin and proteoglycan are mutually exclusive. PMID- 1521533 TI - Dimerization and reactivation of triosephosphate isomerase in reverse micelles. AB - The reactivation of the homodimeric enzyme triosephosphate isomerase (TPI) was studied in reverse micelles. The enzyme was denatured in conventional aqueous mixtures with guanidine hydrochloride and transferred to reverse micelles formed with cetyltrimethylammonium bromide, hexanol, n-octane and water. In the transfer step, denatured TPI monomers distributed in single micelles, and guanidine hydrochloride was diluted more than 100 times. Under optimal reactivation conditions, 100% of the enzyme activity could be recovered. The rate of appearance of the catalytic activity increased with the concentration of protein, which indicated that catalysis required the formation of the dimer. The rate of TPI reactivation also increased with increasing protein concentration in the system with denatured TPI covalently derivatized at the catalytic site with the substrate analogue 3-chloroacetol phosphate. Thus, reactivation could take place via the formation of dimers composed of an inactive and an active subunit. Reactivation critically depended on the amount of water in the reverse micelles. The plot of the extent of reactivation versus the amount of water (2.5-7.0%) was markedly sigmoidal. Less than 20% reactivation took place with water concentrations below 3.5%, due to the formation (in less than 30 s) of stable inactive structures. The results indicate that reverse micelles provide a useful system to probe the events involved in the transformation of unfolded monomers to polymeric enzymes. PMID- 1521534 TI - Three-dimensional structure of phenylalanyl-transfer RNA synthetase from Thermus thermophilus HB8 at 0.6-nm resolution. AB - The three-dimensional structure of the heterodimeric alpha 2 beta 2 enzyme phenylalanyl-tRNA synthetase from Thermus thermophilus HB8 has been determined by X-ray crystallography, using the multiple-isomorphous-replacement method at 0.6 nm resolution. Trigonal crystals of space group P3(2)21 have cell dimensions a = b = 17.6 nm and c = 14.2 nm. Assuming one heterodimeric molecule/asymmetric unit, the ratio of unit cell volume/molecular mass was V = 0.00244 nm3/Da, which is in the middle of the range normally observed. However, after a rotation-function calculation and measurement of the density of the native crystals, we postulate the existence of only the alpha beta dimer in the asymmetric units. This implies 73% solvent content in the unit cell. Three heavy-atom derivatives [K2PtCl4, KAu(CN)2 and Hg(CH3COO)2] and the solvent-flattening procedure were used for electron-density-map calculations. This map confirmed our hypothesis and revealed a remarkably large space filled by solvent, with alpha beta dimer only in the asymmetric unit. The phenylalanyl-tRNA synthetase from T. thermophilus molecule has a 'quasi-linear' subunit organization. As can be concluded at this level of resolution, there is no contact between small alpha subunits in the functional heterodimer. PMID- 1521535 TI - Mechanistic studies of 3-deoxy-D-manno-2-octulosonate-8-phosphate synthase from Escherichia coli. AB - The anomeric specificity and the steady-state kinetic mechanism of homogeneous 3 deoxy-D-manno-2-octulosonate-8-phosphate (KDO8P) synthase were investigated. The open-chain 4-deoxy analogue of arabinose-5-phosphate (Ara5P), which is structurally prohibited from undergoing ring closure, was synthesized and tested as a substrate for the synthase. It was found that the analogue functions as a substrate with a similar kcat value to that of the original substrate. The kcat/Km value for the natural substrate is seven-times greater than that of the 4 deoxy analogue. However, taking into account the 9.5% and approximately 1% concentrations of the aldehyde forms of the 4-deoxy analogue and Ara5P in solution, then the 'true' Km values must be in the range 31.5 microM and 0.26 microM, respectively, requiring about a 3 kcal/mol contribution to the binding energy by the 4-hydroxyl group of Ara5P. The data provides evidence that the enzyme acts upon the acyclic form of the natural substrate. The steady-state kinetic study of KDO8P synthase was analyzed via inhibition using the products KDO8P and inorganic phosphate, and D-ribose-5-phosphate as a dead-end inhibitor. First, intersecting lines in double-reciprocal plots of initial-velocity data at substrate concentrations in the micromolar range suggest a sequential mechanism for the enzyme-catalyzed reaction. The inhibition by D-ribose-5-phosphate is competitive for Ara5P and uncompetitive for phosphoenolpyruvate (P-pyruvate). These inhibition patterns are consistent with the model wherein P-pyruvate binding precedes that of Ara5P binding. Furthermore, this order of substrate binding was supported by the observations that KDO8P is a competitive inhibitor for P-pyruvate binding, supporting the concept that KDO8P and P-pyruvate bind to the same enzyme form, and noncompetitively with respect to Ara5P. In addition, the inhibition by inorganic phosphate is noncompetitive with respect to both P pyruvate and Ara5P, suggesting an apparent ordered release of products such that Pi first, followed by KDO8P. In conclusion, these data suggest a steady-state kinetic mechanism for KDO8P synthase where P-pyruvate binding precedes that of Ara5P, followed by the ordered release of inorganic phosphate and KDO8P. PMID- 1521536 TI - Effect of substrate structure on the activity of Man9-mannosidase from pig liver involved in N-linked oligosaccharide processing. AB - Man9-mannosidase, an alpha 1,2-specific enzyme located in the endoplasmic reticulum and involved in N-linked-oligosaccharide processing, has been isolated from crude pig-liver microsomes and its substrate specificity studied using a variety of free and peptide-bound high-mannose oligosaccharide derivatives. The purified enzyme displays no activity towards synthetic alpha-mannosides, but removes three alpha 1,2-mannose residues from the natural Man9-(GlcNAc)2 substrate (M9). The alpha 1,2-mannosidic linkage remaining in the M6 intermediate is cleaved about 40-fold more slowly. Similar kinetics of hydrolysis were determined with Man9-(GlcNAc)2 N-glycosidically attached to the hexapeptide Tyr Asn-Lys-Thr-Ser-Val (GP-M9), indicating that the specificity of the enzyme is not influenced by the peptide moiety of the substrate. The alpha 1,2-mannose residue which is largely resistant to hydrolysis, was found to be attached in both the M6 and GP-M6 intermediate to the alpha 1,3-mannose of the peripheral alpha 1,3/alpha 1,6-branch of the glycan chain. Studies with glycopeptides varying in the size and branching pattern of the sugar chains, revealed that the relative rates at which the various alpha 1,2-mannosidic linkages were cleaved, differed depending on their structural complexity. This suggests that distinct sugar residues in the aglycon moiety may be functional in substrate recognition and binding. Reduction or removal of the terminal GlcNAc residue of the chitobiose unit in M9 increased the hydrolytic susceptibility of the fourth (previously resistant) alpha 1,2 mannosidic linkage significantly. We conclude from this observation that, in addition to peripheral mannose residues, the intact chitobiose core represents a structural element affecting Man9-mannosidase specificity. A possible biological role of the enzyme during N-linked-oligosaccharide processing is discussed. PMID- 1521537 TI - Conversion, by limited proteolysis, of an archaebacterial citrate synthase into essentially a citryl-CoA hydrolase. AB - 1. Limited proteolysis of citrate synthase from Sulfolobus solfataricus by trypsin reduced the rate of the overall reaction (acetyl-CoA + oxaloacetate + H2O ---citrate + CoASH) to 4% but did not affect the hydrolysis of citryl-CoA. Experimental results indicate that a connecting link between the enzyme's ligase and hydrolase activity becomes impaired specifically on treatment with trypsin. Other proteolytic enzymes like chymotrypsin and subtilisin inactivated catalytic functions of citrate synthase, ligase and hydrolase, equally well. 2. Tryptic hydrolysis occurs at the N-terminal region of citrate synthase, but a study by SDS/PAGE revealed no difference in molecular mass between native and proteolytically nicked citrate synthase. The peptide removed from the enzyme by trypsin, therefore, contains less than about 15 amino acid residues. 3. The Km values of the substrates for both native and nicked enzyme were identical, as was the state of aggregation (dimeric) of the two enzyme species. These could be separated by affinity chromatography on Blue-Sepharose and differentiated by their isoelectric points (pI = 6.68 +/- 0.08 and pI = 6.37 +/- 0.03 for native citrate synthase and the large tryptic peptide, respectively) as well as by the N terminus which is blocked in the native enzyme only. 4. Edman degradation of the large tryptic fragment yielded the N-terminal sequence GLEDVYIKSTSLTYIDGVNGVLRY, which is 71% identical to the N-terminal region (positions 9-32) of citrate synthase from Thermoplasma acidophilum. 5. The conversion of citrate synthase into essentially a citryl-CoA hydrolase is considered the consequence of a conformational change thought to occur on tryptic removal of the N-terminal small peptide. PMID- 1521538 TI - Site-specific mutagenesis of Escherichia coli asparaginase II. None of the three histidine residues is required for catalysis. AB - Site-specific mutagenesis was used to replace the three histidine residues of Escherichia coli asparaginase II (EcA2) with other amino acids. The following enzyme variants were studied: [H87A]EcA2, [H87L]EcA2, [H87K]EcA2, [H183L]EcA2 and [H197L]EcA2. None of the mutations substantially affected the Km for L-aspartic acid beta-hydroxamate or impaired aspartate binding. The relative activities towards L-Asn, L-Gln, and l-aspartic acid beta-hydroxamate were reduced to the same extent, with residual activities exceeding 10% of the wild-type values. These data do not support a number of previous reports suggesting that histidine residues are essential for catalysis. Spectroscopic characterization of the modified enzymes allowed the unequivocal assignment of the histidine resonances in 1H-NMR spectra of asparaginase II. A histidine signal previously shown to disappear upon aspartate binding is due to His183, not to the highly conserved His87. The fact that [H183L]EcA2 has normal activity but greatly reduced stability in the presence of urea suggests that His183 is important for the stabilization of the native asparaginase tetramer. 1H-NMR and fluorescence spectroscopy indicate that His87 is located in the interior of the protein, possibly adjacent to the active site. PMID- 1521539 TI - Matrix NADH dehydrogenases of plant mitochondria and sites of quinone reduction by complex I. AB - In order to distinguish the pathways involved in the oxidation of matrix NADH in plant mitochondria, the oxidation of NADH and nicotinamide hypoxanthine dinucleotide (reduced form) was investigated in submitochondrial particles prepared from beetroot (Beta vulgaris L. cv. Derwent Globe) and soybeans (Glycine max L. cv. Bragg). Nicotinamide-hypoxanthine-dinucleotide(reduced form)-oxidase activity was more strongly inhibited by rotenone than the NADH-oxidase activity but both of the rotenone-inhibited activities could be stimulated by adding ubiquinone-1. The corresponding ubiquinone-1-reductase activities were inhibited by rotenone (to 69%) and further inhibited by N,N'-dicyclohexylcarbodiimide (to 79%), whilst the K3Fe(CN)6-reductase activities were not sensitive to either rotenone or N,N'-dicyclohexylcarbodiimide. Immunological analysis of mitochondrial proteins using an antiserum raised against purified beetroot complex I indicated very few differences between soybean and fresh and aged beetroot mitochondria, despite their varying sensitivities to rotenone. We confirm that there are two dehydrogenases capable of oxidising internal NADH and that only one of these, namely complex I, is inhibited by rotenone. Further, we conclude that complex I has two potential sites of quinone reduction, both sensitive to N,N'-dicyclohexycarbodiimide inhibition but only one of which is sensitive to rotenone inhibition. PMID- 1521540 TI - H2-forming methylenetetrahydromethanopterin dehydrogenase, a novel type of hydrogenase without iron-sulfur clusters in methanogenic archaea. AB - A novel hydrogenase has recently been found in methanogenic archaea. It catalyzes the reversible dehydrogenation of methylenetetrahydromethanopterin (CH2 = H4MPT) to methenyltetrahydromethanopterin (CH identical to H4MPT+) and H2 and was therefore named H2-forming methylenetetrahydromethanopterin dehydrogenase. The hydrogenase, which is composed of only one polypeptide with an apparent molecular mass of 43 kDa, does not mediate the reduction of viologen dyes with either H2 or CH2 = H4MPT. We report here that the purified enzyme from Methanobacterium thermoautotrophicum exhibits the following other unique properties: (a) the colorless protein with a specific activity of 2000 U/mg (Vmax) did not contain iron-sulfur clusters, nickel, or flavins; (b) the activity was not inhibited by carbon monoxide, acetylene, nitrite, cyanide, or azide; (c) the enzyme did not catalyze an isotopic exchange between 3H2 and 1H+; (d) the enzyme catalyzed the reduction of CH identical to H4MPT+ with 3H2 generating [methylene-3H]CH2 = H4MPT; and (e) the primary structure contained at most four conserved cysteines as revealed by a comparison of the DNA-deduced amino acid sequence of the proteins from M. thermoautotrophicum and Methanopyrus kandleri. None of the four cysteines were closely spaced as would be indicative for a (NiFe) hydrogenase or a ferredoxin-type iron-sulfur protein. Properties of the H2-forming methylenetetrahydromethanopterin dehydrogenase from Methanobacterium wolfei are also described indicating that the enzyme from this methanogenic archaeon is very similar to the enzyme from M. thermoautotrophicum with respect both to molecular and catalytic properties. PMID- 1521541 TI - Cytochrome P-450 induction in human lung tumor-derived cell lines. Characterisation and effects of inflammatory mediators. AB - Cytochrome P-450 species (P-450) comprise a polymorphic multigene family of heme containing enzymes which are essential to the phase-I metabolism of xenobiotics. Induction of P-450 species by drugs and carcinogens has been extensively studied; endogenous regulation of P-450 also occurs during normal development and disease. The aim of this project was to study the in-vitro induction of P-450 and its modulation by inflammatory mediators in the human lung tumor-derived cell lines NCI H322 and NCI H358. The cell lines expressed detectable levels of 7 ethoxyresorufin O-deethylase which could be induced by benzanthracene. After benzanthracene treatment, a protein tentatively identified as isozyme CYP1A1 was detected by Western-blot analysis and a concommitant increase in CYP1A mRNA expression was observed. Optimal induction was observed at a benzanthracene concentration of 5 micrograms/ml with cells grown in RPMI medium containing 10% fetal calf serum. The effects of endotoxin, dexamethasone and five recombinant DNA-derived cytokines, interleukin-1 beta, tumor necrosis factor, and interferons alpha, beta and gamma, on constitutive and benzanthracene-induced ethoxyresorufin O-deethylase activity were examined in NCI H322 cells. Of all the lymphokines studied, only interferon gamma had any marked effect. Administration of this lymphokine strongly suppressed ethoxyresorufin O-deethylase activity in both control and benzanthracene-treated cells. PMID- 1521542 TI - Differentiation-inducing-factor dechlorinase, a novel cytosolic dechlorinating enzyme from Dictyostelium discoideum. AB - Differentiation-inducing factor 1 (DIF-1) is a dichlorinated alkyl phenone (1 [(3,5-dichloro-2,6-dihydroxy-4-methoxy)phenyl]hexan-1-one) from Dictyostelium discoideum, that induces amoebae to differentiate into stalk cells. It was shown previously that DIF-1 is rapidly metabolized into a series of more polar compounds by living cells [Traynor, D. & Kay, R.R. (1991) J. Biol. Chem. 266, 5291-5297]. The first step in DIF-1 metabolism is the formation of DIF metabolite 1 (now known to be DIF-3) by a monodechlorination. We report here the discovery of the enzyme activity catalyzing this dechlorination. A very sensitive enzyme assay was developed, using [3H]DIF-1 and a TLC system to separate DIF-1 from the product, DIF-3. DIF-1 3(5)-dechlorinase is present in the high-speed supernatant of cell lysates, and uses glutathione, at physiological concentrations, as cofactor. Kinetic measurements indicate a Km for DIF-1 of about 70 nM. The enzyme activity is inhibited by DIF-2 (the pentan-1-one analogue of DIF-1), with a median inhibitor concentration (IC50) of 1 microM, and DIF-3 (IC50 = 5 microM), which presumably act as substrates, but other compounds structurally related to DIF-1 were much less effective. Aurothioglucose, an inhibitor of selenocysteine enzymes, inhibited DIF-1 3(5)-dechlorinase with IC50 = 100 nM. DIF-1 3(5) dechlorinase activity is developmentally regulated. It is essentially absent from growing cells and increases at the end of aggregation to reach a first peak of activity at the first finger stage, with a further rise at culmination. PMID- 1521543 TI - Analysis of glycosaminoglycan chains from different proteoglycan populations in human embryonic skin fibroblasts. AB - 1. The structure of chondroitin/dermatan and heparan-sulphate chains from various proteoglycan populations derived from cultured human skin fibroblasts have been examined. Confluent cell cultures were biosynthetically labelled with [3H] glucosamine and 35SO4(2-), and proteoglycans were purified according to buoyant density, size and charge density [Schmidtchen, A., Carlstedt, I., Malmstrom, A. & Fransson, L.-A. (1990) Biochem. J. 265, 289-300]. Some proteoglycan fractions were further fractionated according to hydrophobicity on octyl-Sepharose in Triton X-100 gradients. The glycosaminoglycan chains, intact or degraded by chemical or enzymic methods were then analysed by gel chromatography on Sepharose CL-6B, Bio-Gel P-6, ion exchange HPLC and gel electrophoresis. 2. Three types of dermatan-sulphate chains were identified on the basis of disaccharide composition and chain length. They were derived from the large proteoglycan, two small proteoglycans and a cell-associated proteoglycan with core proteins of 90 kDa and 45 kDa. Intracellular, free dermatan-sulphate chains were very similar to those of the small proteoglycans. 3. Heparan-sulphate chains from different proteoglycans had, in spite of small but distinct differences in size, strikingly similar compositional features. They contained similar amounts of D-glucuronate, L-iduronate (with or without sulphate) and N-sulphate groups. They all displayed heparin-lyase-resistant domains with average molecular mass of 10-15 kDa. The heparan-sulphate chains from proteoglycans with 250-kDa and 350-kDa cores were the largest greater than 50 kDa), containing an average of four or five domains, in contrast to heparan-sulphate chains from the small heparan-sulphate proteoglycans which had average molecular mass of 45 kDa and consisted of three or four such domains. Free, cell-associated heparan-sulphate chains were heterogeneous in size (5-45 kDa). 4. These results suggest that the core protein may have important regulatory functions with regard to dermatan-sulphate synthesis. On the other hand, synthesis of heparan sulphate may be largely controlled by the cell that expresses a particular proteoglycan core protein. PMID- 1521544 TI - Measurement of low-molecular-weight antioxidants, uric acid, tyrosine and tryptophan in plaques and white matter from patients with multiple sclerosis. AB - The levels of the antioxidants ascorbic acid, cysteine, reduced glutathione and alpha-tocopherol, of the free-radical marker uric acid and of the amino acids tyrosine and tryptophan were measured by means of high-pressure liquid chromatography in plaques, adjacent white matter and distant white matter from patients with multiple sclerosis, and in central nervous system tissue from patients without neurological diseases. Cholesterol and DNA were also determined, to check demyelination and cellularity. Uric acid was increased and glutathione correspondingly decreased in plaques; alpha-tocopherol was lowest in plaques and highest in distant white matter in all cases. Ascorbic acid, cysteine, tyrosine and tryptophan were not significantly changed in any tissue. The results provide evidence supporting the involvement of free radicals in multiple sclerosis. PMID- 1521545 TI - Spontaneous body sway as a function of sex, age, and vision: posturographic study in 30 healthy adults. AB - Detailed neurological examinations and body sway measurements with a stable force measuring platform were carried out on 30 healthy adults between 21 and 63 years of age. The results were analyzed for sex- and age-associated changes with regard to three different sway components (total sway, anterio-posterior sway, lateral sway) and two different conditions (eyes open, eyes closed). Sex-associated differences were highly significant for all sway components in the oldest age group (51-65 years) in which men exhibited more spontaneous postural sway than women in the condition eyes open. With eyes closed these differences increased. Middle-aged men (36-50 years) also exhibited significantly more postural sway than women of the same age. In the condition eyes open especially total sway and anterioposterior sway were increased, whereas in the condition eyes closed total sway and lateral sway were predominantly higher in men than in women. In the youngest age group (21-35 years) no sex-related differences in postural sway were found. Age-associated differences were significant for anterioposterior sway (eyes open) in men, increasing continuously from the young to the middle-aged, and again from the middle-aged to the older age group. Anterioposterior sway in women, on the contrary, did not change with age. Age-associated differences in women were found for total sway (eyes open) and lateral sway (eyes closed). However, the highest values for total sway and lateral sway within the female group were obtained from young women in both conditions eyes open and eyes closed.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1521546 TI - Intracranial paramedian hourglass-shaped dermoid associated with hereditary steatocystoma multiplex. AB - This is the first report to describe the coexistence of two rare diseases, intracranial paramedian hourglass-shaped dermoid and steatocystoma multiplex. A 46-year-old female with a history of steatocystoma multiplex, bradydactylies and kyphosis showed oscillopsia, ataxia and hemifacial spasm. MRI findings suggested a giant dermoid cyst extending from the left middle temporal fossa to the cerebellopontine angle, and this was confirmed surgically. We propose the involvement of some genetic factor or pathological process common to both disorders, steatocystoma multiplex and dermoid. From the clinical point of view, patients with cystic skin lesion should also be checked for intracranial lesion. PMID- 1521547 TI - Segmental myoclonus preceding herpes zoster radiculitis. AB - Segmental myoclonus arising in the spinal cord occurs with several viral infections, including herpes zoster radiculitis. Usually, abnormal movements follow the rash and require drug treatment to suppress. We report a patient with AIDS in whom arm and shoulder myoclonus preceded herpes zoster involving the same segments contralaterally on two occasions. Myoclonus remitted promptly with antiviral treatment. Unlike in other immunosuppressed patients, encephalitis did not occur after the second episode. PMID- 1521548 TI - Lipoma of the cauda equina selectively involving lower sacral roots. Case report. AB - A 44-year-old male patient suffering from sexual and voiding dysfunction did not exhibit any sensorimotor deficit except for a lax anal sphincter with loss of the bulbocavernosus reflex (BCR). The absence of both the electrically induced BCR and cortical evoked responses to stimulation of the dorsal penile nerve as well as partial denervation of the pelvic floor musculature suggested damage to the lower sacral roots. The site of the lesion as indicated by electrophysiological findings was confirmed by computerized tomography and magnetic resonance imaging. The operation revealed a lipoma involving a few cauda fibers which produced a distension in the region of the conus medullaris. PMID- 1521549 TI - Superficial siderosis of the central nervous system: neuroradiological evaluation of two cases. AB - We present 2 cases of superficial siderosis of the central nervous system secondary to chronic subarachnoid bleeding. The diagnosis was made with MR and cerebrospinal fluid (CSF) examination. MR showed, in T2-weighted images, superficial hypointensity of the cervical cord, brainstem, cerebellum, and basal cisterns due to hemosiderin deposits. CSF was xanthochromic, with increased protein content. In 1 of the 2 cases also the CT examination was positive, showing a hyperdense rim around the brainstem. A complete neuroradiological evaluation (MR, CT, angiography and myelography) did not permit to detect the source of the bleeding. PMID- 1521550 TI - Thermal thresholds and motor sensory conduction measurements in Guillain Barre syndrome: 12-month follow-up study. AB - We performed serial neurophysiological tests in 22 patients with confirmed Guillain Barre syndrome (GBS) for 12 months following onset of the disease. Twenty-five age- and sex-matched healthy controls were also tested. Tests included nerve conduction and automated quantitative thermal threshold measurements. The commonest early abnormality was delayed distal motor latency, F wave abnormality and abnormal thermal threshold measurements in 1 or more nerves. Further abnormalities of all measurements were observed during maximum disability. After 12 months, all measured parameters returned to normal levels in the majority of patients except the thermal thresholds which remained abnormal in a large proportion of asymptomatic patients. The findings are suggestive of an early pathological involvement of the smaller nerve fibres with slow recovery in GBS. PMID- 1521551 TI - Circulating autoantibody to muscle protein in a patient with paraneoplastic myositis and colon cancer. AB - A muscle-specific autoantibody was found in a patient with paraneoplastic myositis and colon cancer. By immunoblotting, we found high titers of circulating antibody to a 34-kDa neutral protein in the soluble sarcoplasmic fraction of the rat skeletal muscle. The serum did not react at all with other tissue extracts including the central nervous tissue, liver, or kidney. The possible role of this muscle-specific autoantibody in the pathogenesis of paraneoplastic myositis is discussed. PMID- 1521552 TI - Chronic Mycobacterium avium complex infection of the central nervous system in a nonimmunosuppressed woman. AB - We report the case of a woman who developed chronic meningitis and a brain abscess due to Mycobacterium avium, without immunosuppressed state. She was treated with antituberculous drugs but the infection progressed and she died 4 years after first becoming ill. The occurrence of CNS infection with M. avium in the absence of acquired immunosuppression is rare. Its diagnosis is difficult, delaying clinical recognition and appropriate therapy. PMID- 1521553 TI - Focal involvement and lateralization in Creutzfeldt-Jakob disease: correlation of clinical, electroencephalographic and neuropathological findings. AB - Focal involvement can be assumed in the initial stage of Creutzfeldt-Jakob disease (CJD). We correlated the clinical, electroencephalographic and neuropathological findings in 13 cases of CJD with special reference to focal or lateralized changes. Eight cases showed clinical and 9 electroencephalographic signs of asymmetry. Four cases with a course of the disease shorter than 12 months presented circumscribed tissue alterations at autopsy. Cases with a clinical duration longer than 12 months had pathological changes involving both hemispheres symmetrically. The infectious agent seems to spread through the entire brain within a period of 12 months. PMID- 1521554 TI - Lovastatin/gemfibrozil myopathy: a clinical, histochemical, and ultrastructural study. AB - Lovastatin has been used with increasing frequency over the past few years to reduce serum cholesterol. The onset of muscle weakness, one of the most serious side effects of long-term treatment with the drug, constitutes a contraindication to the continuation of therapy and commonly occurs in patients who are also receiving gemfibrozil or cyclosporine. We report the clinical and pathologic findings in a patient treated for hypercholesterolemia with lovastatin and gemfibrozil who developed a rapidly progressive necrotizing myopathy. A 57-year old woman with hyperlipidemia, treated with lovastatin and gemfibrozil, was admitted to the hospital for evaluation of muscular weakness in her legs and neck. Neurologic examination revealed severe proximal muscle weakness involving both upper and lower extremities as well as proximal muscle tenderness and areflexia in the lower limbs. A biopsy of the quadriceps muscle showed multiple foci of mononuclear cell infiltration with myophagocytosis and slight variation in the size and shape of muscle fibers. Electron microscopy of the affected fibers showed accumulations of subsarcolemmal autophagic lysosomes. The patient's condition dramatically improved after discontinuation of lovastatin-gemfibrozil therapy. PMID- 1521555 TI - Herald facial numbness. AB - Three unusual patients who developed subacute facial numbness as the heralding symptom of an expanding tumor that involved the trigeminal nerve fibers are reported. The first patient had clinical and electrophysiological evidence of an isolated mental neuropathy as a result of metastatic lesions with bone destruction from a renal cell carcinoma. The second patient had a sensorimotor trigeminal neuropathy caused by a direct compression of the semilunar ganglion by a cavernous hemangioma of Meckel's cave. The last patient experienced facial numbness as the unusual presenting manifestation of a primary brainstem lymphoma. Patients 1 and 3 died a few weeks after the admission, whereas patient 2 poorly recovered. Despite the availability of new techniques for early diagnosis, this report demonstrates how difficult it can initially be to differentiate a 'benign' trigeminal neuropathy from serious conditions and underscores the poor prognosis of fifth nerve fibers involvement by an expanding mass. Early referral with clinical and electrophysiological evaluation appears to be of crucial importance. PMID- 1521556 TI - Relation of aphemia and agraphia. AB - A 49-year-old right-handed man presented with a severe impairment of motor speech output aphemia. Initially, he could make grunting sounds, but was otherwise mute. There was no disturbance of comprehension, and he preferred to communicate by writing. Writing was agrammatic with lexical errors and mispellings which improved with the speech disturbance. The writing abnormalities of aphemics emphasize the aphasic nature of this speech abnormality. PMID- 1521557 TI - Effects of Y-20811, a thromboxane A2 synthetase inhibitor, on experimentally induced coronary thrombosis in anesthetized dogs. AB - The effects of Y-20811, a selective inhibitor of thromboxane A2 (TXA2) synthetase, on blood flow and local levels of immunoreactive thromboxane B2 (i TXB2) and 6-keto prostaglandin F1 alpha (i-6-keto PGF1 alpha) in the coronary artery were investigated in the canine model of coronary thrombosis. Thrombosis was induced by applying an electric current to the intraluminal surface of the coronary artery. The plasma levels of i-TXB2 and i-6-keto PGF1 alpha were measured distal to the electrode. In the control group, coronary blood flow decreased and finally stopped 207 +/- 53 min (mean +/- S.E.M., n = 5) after the start of current application. The level of i-TXB2 rose before the coronary occlusion. Coronary blood flow did not change significantly in the Y-20811 treated group (1 mg/kg i.v.). The level of i-TXB2 decreased and remained significantly lower than that in the control group. The level of i-6-keto PGF1 alpha tended to increase slightly in the Y-20811-treated, but not in the control group. The weight of the thrombus in the Y-20811-treated group was significantly less than that in the control group (P less than 0.01). These results suggest that Y-20811 prevents coronary thrombosis by the inhibition of TXA2 production around the electrically injured lumen of the coronary artery. PMID- 1521558 TI - Cardioprotective effect of pindolol in ischemic-reperfused isolated rat hearts. AB - The effects of pindolol and timolol on ischemia reperfusion damage were studied in isolated working rat hearts. Ischemia (15 min) decreased the mechanical function and the energy state, and increased the tissue levels of free fatty acids (FFA). During reperfusion (20 min), the mechanical function did not recover, but the energy state recovered incompletely, whereas FFA increased further. Pindolol (50 microM) accelerated recovery of the mechanical function and the energy state that had been decreased by ischemia during reperfusion, and inhibited the accumulation of FFA during ischemia and reperfusion, especially when it was applied during the whole period of reperfusion. Timolol (50 microM), however, did not accelerate recovery of the mechanical function and the energy state during reperfusion, although it attenuated FFA accumulation during reperfusion. The pindolol-induced recovery of the mechanical function during reperfusion was reduced by timolol. The results suggest that the intrinsic sympathomimetic activity of pindolol may play an important role, at least in part, in producing the cardioprotective effect, especially during reperfusion. PMID- 1521559 TI - Vasodepressor mechanisms of 2-(1-octynyl)-adenosine (YT-146), a selective adenosine A2 receptor agonist, involve the opening of glibenclamide-sensitive K+ channels. AB - The vasodepressor mechanism of 2-(1-octynyl)-adenosine (YT-146), a selective adenosine A2 receptor agonist, was compared with that of adenosine in spinally anaesthetized dogs whose blood pressure was kept elevated with i.v. infusion of noradrenaline. Cumulative i.v. administration of YT-146 (1-1000 nmol/kg) caused a slowly developing and long-lasting decrease in mean blood pressure (MBP) and a small decrease in heart rate (HR) at high doses, whereas single i.v. administration of adenosine caused short-lived decreases in MBP and HR. In dogs given glibenclamide (6 mumol/kg i.v.) or theophylline (30 mumol/kg i.v.) dose response curves for decrease in MBP due to YT-146 underwent parallel rightward shifts. The ED50 values for YT-146 were increased about 5.5-fold with glibenclamide and about 11.9-fold with theophylline. However, no further rightward shifts of the curves were obtainable in dogs given glibenclamide plus theophylline; the increase in ED50 values for YT-146 was about 6.8-fold, being close to the increase obtained with theophylline alone. The ED50 values for adenosine to lower MBP increased about 1.6-fold with theophylline but not with glibenclamide. Glibenclamide and theophylline failed to antagonize the negative chronotropic effects of both drugs. These results suggest that the vasodepressor effect of YT-146 involves two mechanisms following stimulation of adenosine A2 receptors; one is probably a cyclic AMP-dependent mechanism and the other is the opening of glibenclamide-sensitive K+ channels. PMID- 1521560 TI - Effect of DL-propranolol on nitric oxide production in perfused rat hindquarters. AB - The effect of DL-propranolol on NO release in perfused rat hindquarters was studied by using oxyhemoglobin as a capture system to allow the quantitative assay of NO production. In some experiments the stable prostacyclin metabolite 6 keto-PGF1 alpha (6-keto) was simultaneously assayed. We observed that: (1) DL propranolol induced an increase in NO and 6-keto release. The dextro isomer was inactive; (2) DL-propranolol-induced NO release was only slightly reduced by acetylsalicylic acid in a concentration that inhibits prostacyclin synthesis, and was abolished by the chemical removal of the endothelium with 3-3 cholamidopropyl dimethylammonium 1-propane sulphonate (CHAPS) applied before or during stimulation; (3) NG-nitro-L-arginine blocked DL-propranolol-induced NO production, an effect that was antagonized by L-arginine but not by its dextro isomer. PMID- 1521561 TI - In vivo visualization of central muscarinic receptors using [11C]quinuclidinyl benzilate and positron emission tomography in baboons. AB - The muscarinic antagonist, quinuclidinyl benzilate (QNB), labeled with carbon 11 was used as a radioligand to visualize in vivo by positron emission tomography (PET) the central muscarinic acetylcholine receptors (mAChR) in baboons (Papio papio). The binding characteristics of [11C]QNB showed its specific binding to central mAChR. [11C]QNB brain uptake was high in cerebral cortex and striatum, areas that are rich in mAChR, whereas it decreased rapidly in cerebellum, evidencing non-specific binding in this structure that is almost devoid of mAChR. These results are consistent with the known cerebral distribution of mAChR in primates. [11C]QNB specific cerebral binding was enhanced by pretreatment with methyl-QNB, a peripherally acting muscarinic antagonist. Specifically labeled binding sites alone were blocked by prior administration of dexetimide, a muscarinic antagonist. Specific radioactivity was driven out from mAChR-rich regions by atropine and dexetimide, drugs with high affinity for mAChR. This competition was stereospecific since only dexetimide, the pharmacologically active isomer of benzetimide, was able to compete with the radioligand on its binding sites. A relationship between the occupancy of [11C]QNB-labeled receptors by atropine or dexetimide and the concomitant induction of a pharmacological effect was also detected by simultaneous PET scanning and electroencephalographic recording. Since mAChR form an important part of choline receptors in the central nervous system, [11C]QNB appears to be a suitable radiotracer to monitor cerebral physiological or pathological phenomena linked to the cholinergic system in living subjects. PMID- 1521562 TI - The involvement of products of the phospholipase pathway in the acute release of tissue-type plasminogen activator from perfused rat hindlegs. AB - Using a perfused rat hindleg system, release of tissue-type plasminogen activator (t-PA) from endothelial cells could be induced by platelet-activating factor (PAF), bradykinin, substance P, thrombin, carbachol and A23187, while this release was inhibited by mepacrine and by nor-dihydroguaiaretic acid. The PAF induced release of t-PA was inhibited by the cytochrome P-450 mono-oxygenase inhibitors, metyrapone, ketoconazole and SKF 525A and by eicosatetraynoic acid but not by indomethacin or BW 755C, suggesting the involvement of epoxygenase products. The PAF-induced release of von Willebrand factor (vWF) was also similarly inhibited by the cytochrome P-450 monooxygenase inhibitor, ketoconazole. Phorbol ester and phospholipase C induced the release of both t-PA and vWF, while phospholipase A2 did not. The release induced by PAF and bradykinin was not influenced by pretreatment with pertussis toxin. PMID- 1521563 TI - Role of 5-HT1-like receptors in the increase in intragastric pressure induced by 5-hydroxytryptamine in the rat. AB - The study concerned the effects of 5-hydroxytryptamine (5-HT) on intragastric pressure in bilaterally vagotomized spinal rats. Intravenous (i.v.) bolus injections of 5-HT (2.5, 5.0 and 10 micrograms/kg) produced dose-dependent increases in intragastric pressure; these effects were not modified by atropine (up to 0.2 mg/kg) or mepyramine (1 mg/kg), but were blocked by the mixed 5-HT1 like and 5-HT2 receptor antagonists, methiothepin (0.1, 0.3 and 0.5 mg/kg i.v.) and methysergide (0.5, 1 and 2.5 mg/kg i.v.). However, metergoline (0.5, 1 and 2 mg/kg i.v.) did not markedly modify this effect of 5-HT; only the response induced by 5 micrograms/kg 5-HT was significantly antagonized by the highest dose of metergoline. In contrast, neither the 5-HT2 receptor antagonist, ketanserin (0.5, 1 and 1.5 mg/kg i.v.), nor the 5-HT3 receptor antagonist, ICS 205-930 (0.5, 1 and 3 mg/kg i.v.), influenced the 5-HT-induced increase in intragastric pressure. In addition, 5-carboxamidotryptamine (25, 50 and 100 micrograms/kg i.v.) and RU 24969 (50, 100 and 200 micrograms/kg i.v.) mimicked the aforementioned effects of 5-HT but were weaker than 5-HT. These data suggest that the 5-HT-induced increase in intragastric pressure in the spinal and bilaterally vagotomized rat is mediated by an atypical 5-HT1-like receptor, which, based on the low agonist potency of 5-carboxamidotryptamine and RU 24969 and the resistance to blockade by metergoline, does not seem to correspond to either the 5-HT1A, 5-HT1B, 5-HT1C or the 5-HT1D receptor subtypes. PMID- 1521564 TI - Lysophosphatidic acid induces inward currents in Xenopus laevis oocytes; evidence for an extracellular site of action. AB - Lysophosphatidic acid (LPA) is a naturally occurring phospholipid that can elicit platelet aggregation, smooth muscle contraction and, in fibroblasts, cell proliferation. We now report that LPA in nanomolar concentrations evokes an inward current in native, defolliculated Xenopus laevis oocytes. Extracellular application of LPA from a pressure pipette to the surface of the oocyte induced an immediate response. In contrast, intracellular injection of the same amount of LPA failed to elicit a response. These data suggest the existence of a Ca(2+) mobilizing, endogenous LPA receptor in the Xenopus laevis oocyte cell membrane. PMID- 1521565 TI - Computerized digital image analysis of retinal vessel density: application to normoxic and hyperoxic rearing of the newborn rat. AB - Because of the inherent nature of existing techniques for vascular assessment of the retina, quantitative rigor has been difficult to attain. Computer imaging has now made possible measurement of oxygen-induced alterations in retinal blood vessels that is precise, accurate and repeatable. Newborn rats were exposed to 80% oxygen for 14 days as an animal model for retinopathy of prematurity (ROP). Ink perfusion, followed by retinal dissection, yielded silhouettes of the retinal vascular network. These images were digitized and enhanced by the MegaVision 1024XM imaging system in order to facilitate measuring extent of vasculature and capillary density. Mean grey levels, or 'mu', were 33.1 +/- 3.4 and 20.1 +/- 3.5 for room air- and oxygen-reared rats, respectively. These values are directly proportional to the fraction of the overall image that is vascular material, and, therefore, describe the extent of vaso-obliteration resulting from the oxygen exposure. The values were subsequently converted to square millimeters of vessel area to facilitate comparison to past and future studies. Oxygen rearing does not effect retinal area, but decreases retinal artery and vein diameter and decreases the linear extent of vessels toward the retinal periphery. PMID- 1521566 TI - Glycation of human lens proteins: preferential glycation of alpha A subunits. AB - Glycation of crystallins and high molecular weight (HMW) aggregates was followed during aging (16-85 years) and in diabetes (44 and 70 years old). Lens soluble and insoluble fractions were reduced with [3H]NaBH4 and separated by molecular sieve HPLC. The protein content in each HPLC peak was measured by the Lowry method. The tritium incorporation, expressed as cpm mg-1 protein, was taken as a measure of early glycation and specific non-tryptophan fluorescence (Ex: 370 nm; Em: 440 nm), expressed as relative fluorescence U mg-1 protein, was taken as a measure of advanced glycation. The youngest lenses analysed were 16 and 17 years old and these provided the baseline values. The results showed that during aging there was about a three-fold increase in tritium incorporation and fluorescence of alpha-crystallin, while the increases in beta and gamma were only two-fold from the levels seen in 16- and 17-year-old lenses. On the other hand, both the soluble and insoluble HMW aggregate fractions showed up to five-fold increase in tritium incorporation during aging. The fluorescence was about two-fold higher in the insoluble HMW aggregates as compared to the soluble HMW aggregates in 16- and 17-year-old lenses and both showed an increase of about three-fold during aging. Diabetes resulted in an approximately 10-50% increase in tritium incorporation and non-tryptophan fluorescence of various crystallins and HMW aggregates.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1521567 TI - Ganglion cells in the juvenile chick retina and their ability to regenerate axons in vitro. AB - Ganglion cells in the chicken retina fail to regenerate their axons upon mechanical injury. In order to determine whether this failure to regenerate axons is intrinsic to the neurons or is mediated by the environment, we asked whether ganglion cells possess an ability to regrow their injured axons in the absence of their natural environment, namely in vitro. Since the retina contains morphologically different types of ganglion cells, it became desirable to investigate whether all types of ganglion cells contribute to regeneration of axons. Ganglion cells were labelled post-mortem with the fluorescent dye DiI and described morphologically. Morphometric parameters like the sizes of their perikarya, their dendrites, and the patterns of dendritic ramification and stratification were considered for grouping cells. Although a strong classification of the cells could not be achieved because of the high diversity among this population of neurons, the chick retinal ganglion cells could be separated into seven regular groups which have their somata located within the ganglion cell layer and into one group with the somata located within the inner nuclear layer (displaced ganglion cells). The experimental procedure for regeneration combines crush injury of the chick optic nerve in situ with explanation of retinal pieces 1 week later for organ cultures in a serum-free medium. Under these conditions, the ganglion cells extended axons 1 day after explanation on polylysine/laminin. The densities of ganglion cells contributing to the axonal regrowth reached up to 1447 cells mm-2 (mean 1028 cells mm-2; S.D. 237). This density corresponds to 13% of the ganglion cell density in the normal retina, averaged across the total retina area. Although the dendrites of some cells whose axons had regenerated were altered in comparison with the normal ganglion cells, all morphological types of ganglion cells including those with displaced cell bodies contributed proportionally to the regrowth of axons from the explants. PMID- 1521568 TI - An immunoelectron microscope study of the aged human lens capsule. AB - The distribution of types I-IV collagen and laminin was studied in seven aged human lens capsules using the immunogold EM technique on LR White embedded tissue. Samples were taken from the anterior, equatorial and posterior regions. Labelling for type II collagen was not observed. Type IV collagen was evenly distributed throughout the thickness of the capsule but was absent from the zonules. However, an unexpected finding was strong labelling for types I and III collagen, again evenly distributed throughout the capsule. The presence of type III collagen makes the lens capsule unique among ocular basement membranes. Laminin was present in linear densities, zonular lamellae and zonular fibres, suggesting that linear densities are an integral part of the zonular apparatus. PMID- 1521569 TI - Comparison of ascorbic acid levels in the eye and remainder of the chicken embryo during development. AB - Ascorbic acid was not detectable in egg white and egg yolk of fertilized eggs prior to incubation. It was demonstrated in the embryo at 5 days of incubation and its content in the eyes and other parts of the embryo increased with the embryo's age. Ascorbic acid of the eyes rose rapidly after day 6 during maximal eye growth and reached a peak by days 10-14 when the expansion of the eyes began to level off. Ascorbic acid content of the eyes decreased thereafter, while ascorbic acid in the head and the body tissues continued to rise up to the time of hatching. Whether this rapid increase of ascorbic acid concurrent with the increase of eye diameter indicates a role for ascorbic acid in the growth of the embryonic eye remains to be determined. PMID- 1521570 TI - Proteoglycans in the mouse interphotoreceptor matrix. V. Distribution at the apical surface of the pigment epithelium before and after retinal separation. AB - The distribution of chondroitin sulfate proteoglycans in the mouse interphotoreceptor matrix (IPM) proximal to the retinal pigment epithelium (RPE) was evaluated with EM histochemical techniques using Cupromeronic Blue (CmB) before and after retinal separation. Densely packed, sheet-like processes surrounding vesicle-like compartments containing CmB staining were normal constituents of the IPM at the apical surface of the RPE. Most of the vesicle like compartments, which appeared to be isolated from the IPM in single section profiles, were found to be continuous with the IPM when three-dimensional reconstructions of serial thin sections were evaluated. Analyses of stereo image pairs of semithin sections visualized by electron spectroscopic imaging (ESI) also demonstrated that the CmB stained proteoglycans in the lumen of these pseudovesicles were in continuity with the CmB stained components present in the IPM. Moreover, ESI demonstrated that the CmB stained profiles formed an elaborate interconnecting network extending from the apical border of the RPE to the level of the outer limiting membrane of the retina. After removal of the retina, rinsing of the RPE with Ringer's solution prior to fixation eliminated proteoglycan staining near the base of the apical processes, whereas staining near the tips of these processes remained. The CmB stained filaments remaining after rinsing were thicker and shorter, and made fewer interconnections than those in the non-separated preparations. These results suggest that two types of chondroitin sulfate proteoglycans are present in the IPM which differ in distribution and in the degree of aqueous solubility. Additionally, a closely associated retina appears to be required for maintenance of the normal structure of proteoglycans associated with the RPE surface. The elaborate topography at the RPE apical surface may play a role in the delivery and/or recovery of components of the IPM. PMID- 1521571 TI - Membrane architecture as a function of lens fibre maturation: a freeze fracture and scanning electron microscopic study in the human lens. AB - The ultrastructure of fibre membranes in human lenses, varying in age from premature to 40 years, was investigated using a strict protocol regarding their localization within the lens. The ultrastructural approaches used were scanning electron microscopy (SEM), and transmission electron microscopy (TEM) of ultrathin sections and freeze-fracture replicas. Irrespective of the age of the lens, superficial fibre membranes are characterized by a high density of intramembrane particles (IMPs) and numerous gap junctions (GJs). In contrast deep cortical fibres, at the SEM-level characterized by grooves and ridges, are largely free of IMPs but still contain numerous GJs. In between these regions a transitional zone was observed. At the SEM-level the transitional fibres are characterized by wrinkled membranes and formation of grooves and ridges. In freeze-fracture replicas the presence of numerous square arrays (SAs) associated with GJs is most remarkable. It is concluded that at all ages studied, the maturation and compaction of lens fibres results in a transformation of membrane architecture leading to clear-cut ultrastructural differences between superficial and deep cortical membranes. It is argued that this ultrastructural heterogeneity parallels the gradients observed biochemically for intrinsic membrane proteins and cholesterol:phospholipid ratios. The observations confirm the electrophysiological view that superficial membranes have an 'average' permeability and that deep cortical membranes are 'degenerate' or 'non-leaky'. PMID- 1521572 TI - Detection, quantification, and significance of basic fibroblast growth factor in the aqueous humor of man, cat, dog and pig. AB - By using a highly specific and sensitive heterologous radioimmunoassay, we determined the content of basic fibroblast growth factor (bFGF) in fresh samples of aqueous humor obtained from human (n = 18), feline (n = 8), canine (n = 12), and porcine (n = 10) eyes by paracentesis. The content of bFGF in human aqueous humor ranged from 0.480 to 1.44 ng ml-1 (mean +/- S.D. = 1.074 +/- 0.297 ng ml 1); in feline samples, from 0.672 to 1.152 ng ml-1 (1.016 +/- 0.158 ng ml-1); in canine samples, from 0.640 to 1.232 ng ml-1 (1.026 +/- 0.171 ng ml-1); and in porcine samples, from 0.627 to 0.957 ng ml-1 (0.728 +/- 0.115 ng ml-1). These values were confirmed by means of a dot/slot-blot technique. For all species, the aqueous samples had normal protein levels that ranged from 5 to 19 mg dl-1. There was no correlation of the content of bFGF with the level of protein or with age of the human subjects. The similarity in the concentrations of bFGF in the aqueous humor as well as the stability of the blood-aqueous barriers of all four species indicate that cats, dogs, and pigs can serve as suitable animal models for the study of the role of bFGF in health and disease. We suggest the possible involvement of bFGF in the pathogenesis of anterior-segment disorders, such as neovascular glaucoma, and in the wound-healing response of limbal tissues after glaucoma filtration surgery. PMID- 1521573 TI - Immunohistochemical localization of hyaluronan synthase in cornea and conjunctive of cynomolgus monkey. AB - Distribution of hyaluronan synthase was investigated in cornea and conjunctiva of Cynomolgus monkeys (Macaca fascicularis) using polyclonal antibodies against the streptococcal enzyme. Strong immunoreaction was found in the cell membranes of the corneal endothelium, corneal epithelium, and most of the conjunctival epithelium. In the corneal epithelium all cells except the basal ones stained. In the conjunctiva all cylindrical cells stained, whereas among the goblet cells one type showed intense membrane staining, the other remained unstained. In the limbal portion of the conjunctival epithelium, which in many other respects differs morphologically and functionally from the remaining conjunctiva, all membranes of the different layers of the stratified epithelium except the most superficial ones, appeared unstained. Staining was also seen in all stromal fibroblasts and capillary endothelial cells. PMID- 1521575 TI - Immunolocalization of basic fibroblast growth factor: dependence on antibody type and tissue fixation. PMID- 1521574 TI - Description of an acylpeptide hydrolase from lens. AB - Acylpeptide hydrolase, which catalyses the hydrolysis of blocked N-terminal amino acids from peptide substrates, has been identified in the extracts from beef, human, rabbit and rat lens. In bovine lens sections, lower activity was observed in nuclear and inner cortical regions compared to the outer cortical region. The enzyme from bovine lens showed a high molecular weight nature, eluting between alpha and beta crystallins during Sephadex G-200 chromatography. The activity has a pH optimum around 7.8 when assayed with N-acetyl-Ala-p-NA as substrate. The enzyme was capable of hydrolyzing a variety of blocked peptides including N acetyl-(Ala)2, Me-O-Suc-Ala-Ala-Pro-Val-p-NA, N-Acetyl-Met-Leu-Phe, Acetyl-Ser Gln-Asn-Tyr and N-formyl-Met-p-NA. In each case the enzyme released an N-blocked amino acid and exposed a free amino group as judged by thin layer chromatography. Neither Ala-p-NA nor N-acetyl-Ala were hydrolysed by the same enzyme preparation. The enzyme activity from human and bovine lens was completely inhibited by DFP, and partially inhibited by PMSF, penicillin-G and ampicillin. These preliminary results show that lens tissue has an active acylpeptide hydrolase, however, a partially purified enzyme preparations was not able to cleave the acetyl-Met- from native alpha A-crystallin in vitro suggesting that the N-terminus of native crystallins is not accessible to the enzymes. PMID- 1521576 TI - Identification of 3-hydroxykynurenine as the lens pigment in the gourami Trichogaster trichopterus. PMID- 1521577 TI - Proenkephalin A derivatives in lacrimal gland: occurrence and regulation of lacrimal function. AB - The derivatives of proenkephalin A were measured in acid extracts of rat lacrimal glands by specific radioimmunoassay. Glands from adult male rats contained all four derivatives of the opiate precursor. The content in the gland of proenkephalin A-derived peptides Met5-enkephalin, Leu5-enkephalin, Met5 enkephalin Arg6-Phe7 and Met5-enkephalin Arg6-Gly7-Leu8 indicates tissue specific processing with an enhancement of the heptapeptide. The effect of enkephalins on the activity of adenylate cyclase in lacrimal membranes was measured and compared with the effect of the synthetic enkephalin analogue D-ala2-methionine enkephalinamide (DALA) that inhibits both lacrimal protein secretion and lacrimal adenylate cyclase. In the presence of the peptidase inhibitors thiorphan and bestatin, the inhibition of forskolin-stimulated adenylate cyclase activity by Met5-enk, Leu5-enk, Met5-enk Arg6-Phe7 and DALA were identical. Maximum inhibition was approximately 35% at a dose of 50 microM enkephalin. Addition of the octapeptide, Met5-enk Arg6-Gly7-Leu8 resulted in decreased adenylate cyclase activity; however, the effect was not statistically significant. Activation of delta opioid receptors by the endogenous enkephalins is indicated by the reversal of adenylate cyclase inhibition in the presence of the delta-receptor antagonist ICI 174864. The data support the physiological significance of in vitro inhibition of lacrimal secretion by DALA and indicate a possible role for endogenous enkephalins in lacrimal function. PMID- 1521578 TI - The phagocytosis of ROS by RPE cells is inhibited by an antiserum to rat RPE cell plasma membranes. AB - A polyclonal antiserum to a rat retinal pigment epithelium (RPE) plasma membrane enriched fraction has been utilized to identify candidate receptor proteins which may be involved in the phagocytosis of rod outer segments (ROS) by the RPE. Immunoblots of RPE cell extracts show that the the antiserum recognizes a number of glycoproteins, including two with M(r)s of 174 and 75 kDa. The antiserum also recognizes their non-glycosylated counterparts, with M(r)s of 169 and 65 kDa, respectively, which are synthesized after treatment of the cells with tunicamycin B2. Immuno-precipitation of [35S]-methionine-labeled RPE cell extracts also demonstrates the presence of antibodies to these same glycoproteins as well as to other proteins. The antiserum inhibits the binding of ROS to the RPE, which subsequently results in a decrease in the ingestion of ROS. ROS phagocytosis by the RPE is inhibited by 97% in the presence of a 1:10 dilution of the IgG fraction of the antiserum. Phagocytosis recovers to normal levels after 4-6 hr of chase in the absence of antibodies. After sequential adsorption of the IgG fraction to monolayers of fixed RPE cells, which removes RPE surface-specific IgGs, the extent of inhibition of ROS phagocytosis produced by the IgG fraction is reduced. Using immunoblotting we have identified a number of surface-specific immunoreactive bands which are adsorbed out of the antiserum, including the 174 and 75 kDa bands. These data give further support to the hypothesis that ROS phagocytosis is a receptor-mediated process, which occurs via specific cell surface glycoprotein receptors. PMID- 1521579 TI - Immunocytochemical study of extracellular matrix components during lens and neural retina regeneration in the adult newt. AB - We have conducted an immunocytochemical study of fibronectin, laminin, heparan sulfate proteoglycans and nidogen-entactin during lens and neural retina regeneration in the adult newt from 0 to 60 days. In the normal eye, fibronectin was detected in the corneal stroma and Descemet's membrane, in dorsal and ventral irises and lens capsule but not in Bowman's membrane of the cornea. In normal neural retina, fibronectin was found in Bruch's and inner limiting membranes. Heparan sulfate proteoglycans gave a slight signal in both irises and the lens capsule. Nidogen-entactin distribution in the cornea was similar to that of fibronectin; it was absent from the stroma of both irises, and the signal was weak in the pigmented iris epithelium. Nidogen-entactin was not detected in the lens capsule and inner limiting membrane of the neural retina but was present in Bruch's membrane. During the first 15 days of lens regeneration, fibronectin and nidogen-entactin decreased but did not disappear from the pupillary margin of both irises, and no signal was obtained for laminin and heparan sulfate proteoglycans. From day 15 to day 60 fibronectin and nidogen-entactin increased in both irises and lens capsule. The signal for laminin was restricted to the lens capsule. Heparan sulfate proteoglycans gave a slight signal in both irises and in the lens capsule. During the first 25 days of neural retina regeneration, fibronectin was the first to appear in Bruch's membrane and the cell border of the new neuroepithelium and remained during the entire process. Laminin appeared after 41 days in the inner limiting and Bruch's membranes, but by day 50 it appeared as a weak signal only in the inner limiting membrane. Heparan sulfate proteoglycans were not detected at any of the regeneration stages studied. Nidogen-entactin was only detected in Bruch's membrane and around the cells and blood vessels of the new neural retina. Later it was detected in the inner limiting membrane but not in Bruch's membrane. Thus, the results obtained showed that extracellular matrix components do change during both lens and neural retina regeneration. These changes may play an important role during both regenerating processes. PMID- 1521580 TI - Pressures in the juxtacanalicular tissue and Schlemm's canal in monkeys. AB - A micropuncture technique involving the use of microcannulas with tip diameters less than 5 microns was used to measure the pressure in Schlemm's canal and in the meshwork at distances approximately 7 and 14 microns from the inner wall of Schlemm's canal. In one set of experiments where the spontaneous intraocular pressure (IOP) was 12.2 +/- 0.5 cmH2O and the Schlemm's canal pressure (PSc) was 7.6 +/- 0.7 cmH2O, the pressure at 7 microns from the inner wall of Schlemm's canal was found to be 8.9 +/- 0.7 cmH2O and at a distance of 14 microns, 11.0 +/- 0.5 cmH2O--that is, 1.3 +/- 0.2 and 3.4 +/- 0.3 cmH2O respectively, higher than the PSc. In another set of experiments, the spontaneous IOP and PSc were also measured and then the IOP was increased by means of an external reservoir and measured once again. Spontaneous IOP was 16.0 +/- 1.3 cmH2O and the PSc was 11.5 +/- 1.4 cmH2O before the IOP was increased. After the IOP was increased to 20.2 +/- 1.2 cmH2O, the PSc was 11.7 +/- 1.6 cmH2O. When the microcannula was introduced into the juxtacanalicular tissue to locations at about 7 and 14 microns from the inner wall of Schlemm's canal the pressure measured at 7 microns was 16.9 +/- 1.3 and at 14 microns it was 18.9 +/- 1.4 cmH2O--that is, 5.2 +/- 0.8 and 7.2 +/- 1.0 cmH2O respectively, higher than the PSc. The results indicate that at the spontaneous IOP about 75% of the resistance between the anterior chamber and Schlemm's canal is located within 14 microns from the canal with some 50% being located within the region 7 and 14 microns from the canal. After a small increase in IOP, the tissue causing most of the outflow resistance became relocated to a region within 7 microns from the canal. PMID- 1521581 TI - Identification of a 9 kDa gamma-crystallin fragment in human lenses. AB - The degraded polypeptides (M(r) less than 14 kDa) were isolated by a preparative SDS-PAGE method from water soluble (WS) and water insoluble (WI) proteins of human lenses from donors of ages between 5 and 75 years. SDS-PAGE analysis showed the presence of a major 9 kDa polypeptide species that showed an age-related increase in levels in WS-polypeptide preparations. In order to identify the parent crystallin of the 9 kDa polypeptide, the immunoreactivities of the WS- and WI-degraded polypeptides to immuno-affinity-purified anti-human alpha-, beta- and gamma-crystallin antibodies were determined by the Western blot method. The WS- and WI-9 kDa polypeptides showed immunoreactivity to only the anti-gamma crystallin antibody suggesting it to be a fragment of gamma-crystallin. A 9 kDa species was purified by Sephadex G-50 chromatography from the WS-protein fraction of lenses from 20-30-year-old donors. The purified polypeptide showed a single protein band during SDS-PAGE and also an apparent single spot on two-dimensional gel-electrophoresis (IEF followed by SDS-PAGE). The purified preparation also showed a single major peak during reverse phase HPLC chromatography. The purified 9 kDa polypeptide showed immunoreactivity to only the anti-gamma-crystallin antibody. A polyclonal antibody raised against the purified 9 kDa polypeptide showed immunoreactivity only to a 20 kDa gamma-crystallin species. The partial N terminal sequence analysis of the 9 kDa polypeptide showed it to be a fragment of gamma D-crystallin. Together these results show that a 9 kDa gamma D-crystallin fragment exists in increasing quantities in human lenses during aging. PMID- 1521582 TI - Effect of enzymatic deglycosylation on the regenerability of bovine rhodopsin. AB - The influence of the carbohydrate groups of rhodopsin on its ability to regenerate upon incubation with 11-cis retinaldehyde after photobleaching was examined. Rhodopsin was deglycosylated enzymatically with peptide-N-glycosidase F (PNGase F). Verification of deglycosylation was established by: (a) SDS-PAGE; (b) carbohydrate compositional analysis using high performance anion exchange chromatography with pulsed amperometric detection (HPAEC-PAD); (c) isolation and carbohydrate analysis by HPAEC-PAD and fast atom bombardment-mass spectrometry of the oligosaccharides liberated from rhodopsin; and (d) absence of reactivity with lectins. Deglycosylated rhodopsin, when present either in rod outer segments or after purification, exhibited the same absorption spectrum as the native molecule. After photobleaching, deglycosylated rhodopsin reacted with 11-cis retinaldehyde in a manner similar to the native material, restoring the spectral properties lost after light-exposure. The carbohydrate portion, therefore, was not required for expressing the spectral properties of rhodopsin nor for regeneration of the photobleached visual pigment. PMID- 1521583 TI - Uptake of 22-carbon fatty acids into rat retina and brain. AB - Rat retina accumulates high levels of 22-carbon (C22) polyunsaturated fatty acids (PUFA), especially docosahexaenoic acid (DHA, 22:6 omega 3), in rod outer segment (ROS) phospholipids (PL). However, plasma, the source of retina lipids, is enriched in 20-carbon (C20) fatty acids instead of C22 PUFA. This suggests that the retina has a mechanism(s) for selective uptake of C22 PUFA from the blood. It is not known if the selective uptake is specific for the carbon number alone, or if the number of double bonds is also important. To address this question, the following study was carried out using erucic acid (22:1 omega 9) as a metabolic marker molecule. Albino rats were raised from birth on a diet containing 10% (by weight) of either rapeseed oil (43% 22:1 omega 9) or blended canola oil (0.4% 22:1 omega 9). At 4 months of age, plasma, liver, adrenal gland, brain and retina were collected, lipids were extracted, and fatty acids were determined. In those rats fed rapeseed oil, 22:1 omega 9 was incorporated into the lipids of plasma (2.3%), liver (0.6%), and adrenal gland (17.6%), indicating that this fatty acid was absorbed, transported, and metabolized by the rats. However, 22:1 omega 9 was not incorporated into the lipids of retinal ROS or brain. Our results suggest that both the carbon number and degree of unsaturation are important determinants in the selective uptake of C22 fatty acids from plasma into both the brain and the retina. PMID- 1521584 TI - Evidence for a Na(+)-Cl(-)-H(+)-HCO3- exchange system in the mammalian lens. AB - 36Cl- efflux was studied in the isolated rat lens under two conditions that are known to decrease internal pH. The first follows exposure to a pulse of ammonium chloride (50 mM) and the second accompanies exposure to an acidified propionate (20 mM) solution. Under acidifying conditions, a stimulation in 36Cl- efflux was observed, that was abolished on removing external Na+ and also on removing external Cl- and HCO3-. In the absence of external Cl-, the presence of HCO3- (16 mM) resulted in an increase in 36Cl- efflux during internal acidification. In the absence of internal acidification, the addition of 0.1 mM dibutyrylcAMP or 0.5 mM IBMX to the external medium produced a rapid increase in 36Cl- efflux. This stimulation was reduced by 0.2 mM SITS. Neither cAMP or IBMX had any significant effect on the electrical resistance of the lens membranes. It is suggested that a coupled SITS-sensitive, Na(+)-Cl(-)-H(+)-HCO3- exchange mechanism is activated when the lens internal pH falls and further that cAMP may play a role in regulating this mechanism. PMID- 1521585 TI - Rhodopsin levels in the central retinas of normal miniature poodles and those with progressive rod-cone degeneration. AB - Visual pigment in normal miniature poodles and those with progressive rod-cone degeneration (prcd), a late-onset autosomal recessive photoreceptor degeneration, has been studied using imaging fundus reflectometry (IFR). The stage to which the disease had advanced in the animals with prcd was assessed with electroretinography (ERG). Measurements were carried out on seven affected, two heterozygous and three homozygous normal animals. The IFR measurements showed that the in situ difference spectrum of visual pigment measured in the central retina of the normal poodle is typical of vertebrate rhodopsin, with a maximum at about 510 nm. Rhodopsin regeneration following extensive bleaches continues for up to 70 min. In poodles with prcd, rhodopsin is spectrally normal and regenerates at normal rates. In young affected animals under 1 year of age, the final levels of rhodopsin could already be substantially reduced. Serial measurements of visual pigment in these dogs showed differences in the degree and spatial pattern of pigment loss and rate of progression between animals. The extent of visual pigment loss also differed among the older (greater than 4.5 years) affected animals: while in one animal no pigment could be detected, in another a central band of retina was relatively spared, and significant levels of visual pigment were measured within it. Pigment levels measured within the central 25 degrees of the retinas of poodles heterozygous for prcd were lower than those in normal animals, even though their ERGs were within the normal range. PMID- 1521586 TI - Synthesis and secretion of interphotoreceptor retinoid-binding protein (IRBP) and developmental expression of IRBP mRNA in normal and rd mouse retinas. AB - The synthesis and secretion of interphotoreceptor retinoid-binding protein (IRBP) was quantitatively assessed in retinas of normal and rd mutant mice using short term organ culture with [35S]methionine. Retinas were studied at ages P9-P12, time points prior to and immediately after the onset of the degeneration of the rd retina. Soluble proteins of the retinal pellet and the incubation medium were subjected to SDS-polyacrylamide gel electrophoresis. Analysis of labeled protein bands utilized a radioactivity scanning system to quantify [35S]methionine incorporation into newly synthesized IRBP. The synthesis and secretion into the incubation medium of IRBP by rd mouse retinas was comparable to normal retinas at P9-P10 but decreased by more than 50% by P12. IRBP mRNA levels were evaluated in retinas of normal and rd mice ages P7-P14. Although IRBP mRNA expression increased in the rd mouse through P10, it decreased markedly thereafter. Previously reported immunocytochemical studies suggested that IRBP was not secreted in the rd mouse retina. The results of this study indicate, however, that rd mouse retinas, when removed from the eye, have the capacity to synthesize and secrete IRBP. PMID- 1521587 TI - Morphologic and clinical study of the retinal circulation in the miniature pig. A: Morphology of the retinal microvasculature. AB - The microvasculature of the retina was studied in 20 miniature pigs by means of vascular corrosion casts and semithin histological sections. These techniques provided information useful for a better understanding of retinal fluoangiography. Various characteristics of the porcine retinal vessels, which are similar in the human retinal vasculature, were demonstrated in this study: the holangiotic retina, the trilaminar organization of the retinal capillaries and the presence of particular avascular zones, radial peridiscal capillaries and initial annular constrictions of certain arteriolar side-branches. The intrinsic retinal vasculature also shows some dissimilarities between both species. The major retinal blood vessels of the pig lie very superficially in the nerve fibre layer, in contrast to their deeper location in man. The streak-shaped macular area of the pig contains no major vessels but, unlike the central fovea in the human eye, it is not completely avascular. Another interesting finding is the presence of a large anterior border venule in the porcine retina. PMID- 1521588 TI - Morphologic and clinical study of the retinal circulation in the miniature pig. B: Fluorescein angiography of the retina. AB - The retinal blood circulation was examined in 20 porcine eyes by studying fluoangiograms before and after occlusion of the temporal choroidal circulation. The use of a small intravenous bolus of 2.5 ml fluorescein provided high resolution angiograms with detailed information of the retinal vascular bed. The lobular filling pattern of the choriocapillaris very closely resembles the human pattern. The intrinsic retinal vasculature of the miniature pig also has numerous characteristics in common with the human retina with regard to the extent of the vascular bed, the size of the blood vessels and the presence of radial peridiscal capillaries. Unlike the central fovea in the human eye, the porcine retina has a streak-like macular area which extends both temporally and nasally and which, although it is free of major blood vessels, is not completely avascular. This fluoangiographic study substantiates the results of the accompanying paper. It may be concluded that the miniature pig is a suitable experimental animal for applied research on the retinal vasculature. PMID- 1521589 TI - Recombinant human basic fibroblast growth factor (Rh-bFGF) in three different wound models in rabbits: corneal wound healing effect and pharmacology. AB - Prior to a clinical trial in humans, we studied the effect and pharmacological distribution of recombinant human basic fibroblast growth-factor (Rh-bFGF) in vivo. Healing experiments on de-epithelialized rabbits corneas (n = 24 animals) compared the efficacy of three bFGF doses to controls and revealed a significantly increased healing rate for both 200 ng and 500 ng per application Rh-bFGF treatment groups compared to the control groups. To assess possible side effects of Rh-bFGF (500 ng topically applied for up to 7 days, twice daily), ten rabbits were involved in a model of an anterior keratectomy wound (performed with Draeger's roto-keratome to a depth of 0.15 mm). Light microscopy of thin sections of treated corneas showed an increased fibrogenesis in the anterior stroma with a more pronounced activation of keratocytes. No evidence for abnormal neovascularization or inflammation was observed when compared to control corneas. Ocular penetration and systemic distribution of topically applied labelled 125I FGF was assessed in three models (iodine vapour epithelial burn, anterior keratectomy and penetrating autokeratoplasty) in 24 rabbits. No intraocular penetration of bFGF occurred as shown by direct gamma counting. Macroautoradiography showed a selective labelling of epithelial basement membrane when denuded and intact, as previously described. Evidence for systemic absorption of breakdown products was confirmed by heparin-sepharose chromatography of blood and urine samples. Under these conditions, we suggest that topical Rh-bFGF promotes corneal wound healing without morphological adverse reaction or intraocular and systemic penetration. PMID- 1521590 TI - Electrical fields in the vicinity of epithelial wounds in the isolated bovine eye. AB - A lateral potential drop along the outer surface of the cornea could be measured at the edge of wounds made in the corneal epithelium of the isolated bovine eye when the cornea was covered by simulated tear film of modified Hanks' solution. These lateral fields (LFs) had an average magnitude of 42 +/- 1.4 mV mm-1 in the first 0.25 mm from the wound edge. The polarity of these surface LFs is more positive at the wound than in regions away from the wound. Very little if any lateral field could be measured at the edge of wounds along the inner surface of the corneal epithelium. The surface LFs depend on the cornea's transepithelial potential (TEP), which in this isolated bovine eye preparation we determined (with conventional microelectrode techniques) to have an average value of 24.7 +/ 2.2 mV, stroma-side positive. We found that this TEP drives a current from wounds in the epithelium with an average current density of 55 +/- 12 microA cm 2. We also have found that the average transcorneal potential (TCP) was 3.2 +/- 0.5 mV greater than the average TEP, confirming that the major contribution to the TCP comes from the corneal epithelium. PMID- 1521591 TI - Genetic variability and rodent models of human aging. AB - Inbred strains, outbred strains, and natural populations of rodents differ greatly in the amount and nature of the genetic variability they possess. Consequently, as models of human aging they vary with respect to the areas of research to which they are best suited. Inbred strains, in which all individuals are genetically identical, are best suited as models of specific disease processes and for manipulations involving tissue transplantation. Their lack of genetic variability, however, and the disruption of genetic linkage groups that occurs during inbreeding limit their value as models of more general aging processes. Outbred strains exhibit large interindividual genetic variation--a result of ongoing random accumulation of deleterious alleles with late ages of action. This makes them ideal models for studying the diversity of pathologic lesions, connections between pathologies, and susceptibility to pathologic lesions that collectively produce the reductions in reproductive capacity, physiological efficiency, and viability that are characteristic of aging. Natural populations also may exhibit relatively large amounts of interindividual genetic variability. However, difficulties with husbandry, variable parasite loads, and complex population genetics can compromise their suitability as models of human aging. Ultimately, a consideration of the range of animal models available and a more careful matching of the goals of a study with the genetic system of the model will prove fruitful to gerontology. PMID- 1521592 TI - The reductive capacity index of saliva obtained from donors of various ages. AB - The reducing ability of saliva is decreased with donor age as indicated by cyclic voltammetry measurements of saliva. It has been shown that saliva possesses a strong reducing power that is influenced by the induction of oxidative stress. The exact capacity of saliva to cope with oxidative stress has never been studied in detail. We used a new approach to detect the role of oxidative stress on saliva. This approach included the detection of the total reducing capacity of the saliva without determination of the exact concentration of a specific reducing compound present in the saliva. Induction of oxidative stress resulted in a significant change in the reductive capacity detected. Measurements of the reducing potential of saliva revealed that there is a correlation between the donor age and the reductive capacity observed. Also, saliva obtained from donors in various disease states have shown a significant change in the potential recorded, as compared to controls. The possible use of this method as a diagnostic tool in various diseases is discussed. PMID- 1521593 TI - Effect of cold on serum substrate and glycogen concentration in young and old Fischer 344 rats. AB - This investigation evaluated the hypothesis that the age-related decline in cold induced thermogenesis observed in male (F344) rats is associated with altered substrate concentrations of glucose, lactate, and/or liver and muscle glycogen. Body mass-independent O2 consumption, core temperature, and serum glucose and lactate concentrations were measured at rest and during 4 h of exposure to 5 degrees C in male F344 rats ages 6, 12, and 26 months. At the end of the 4-h cold exposure, liver, soleus, and gastrocnemius tissues were removed, frozen, and analyzed for glycogen concentration and/or citrate synthase activity. Core temperature decreased during cold exposure and was consistently less in the 26 month versus the 6- and 12-month rats. There were no significant differences between the 6- and 12-month-old rats with respect to cold-induced O2 consumption, but measures were significantly lower in the 26-month-old rats. During cold exposure, serum lactate and glucose concentrations increased in the 26-month-old animals compared to those in the 6- and 12-month-old rats, while liver glycogen concentrations decreased in all groups, and gastrocnemius glycogen contents decreased in the 12- and 26-month-old rats. Citrate synthase specific activity (mumol.[min.microgram.protein] -1) did not differ with age. These data suggest that carbohydrate availability (as measured by serum glucose and muscle glycogen) is not a limiting factor in the attenuated cold-exposed thermogenic response of the 26-month-old male F344 rat. However, it appears that the 26-month-old rat may have a diminished capacity to fully oxidize carbohydrate during cold exposure. PMID- 1521594 TI - Lymphoproliferative responses in diet-restricted and aging Sprague-Dawley rats. AB - Immunological effects of aging and dietary restriction (i.e., chronic underfeeding without malnutrition) were investigated in male CFY Sprague-Dawley rats. From weaning, diet-restricted animals were given the amount of food that maintained their body weights at approximately 50% of age-matched ad libitum controls. Cells from the spleen, Peyer's patches, brachial/axillary lymph nodes, and mesenteric nodes of 12- and 20-month-old rats were tested in vitro against the T-cell mitogens phytohaemagglutinin and concanavalin A, and the B-cell mitogen Salmonella minnesota lipopolysaccharide (with dextran sulphate). No clear boosting effect of dietary restriction nor age-related decline in T- or B-cell response was observed when a standard foetal bovine serum supplement was used. In general however, serum from diet-restricted rats supported better proliferative responses than serum from age-matched controls, suggesting that dietary restriction may promote lymphocyte proliferation by an indirect mechanism. A feature of this study was the variation in phenotype and immune responsiveness among closely related animals. Thus in an outbred population, any beneficial effects of dietary restriction upon immune responses could be outweighed by variation among individuals. PMID- 1521595 TI - Changes in conjugative enzyme activity and acetaminophen metabolism in young and senescent male F-344 rats following prolonged exposure to buthionine sulfoximine. AB - This study examined how advanced age affects glucuronide and sulfate conjugation of acetaminophen after prolonged exposure to L-buthionine-S,R-sulfoximine (BSO) in male Fischer 344 rats. Young (4-5 month) and senescent (21-22 month) rats received 11 doses of BSO (2 mmol/kg) at 12-h intervals via a gastric cannula. Hepatic metabolism was assessed in vivo by measuring the products of reactions mainly responsible for acetaminophen elimination, namely the formation of the glucuronide and sulfate conjugates. Selected drug-metabolizing enzyme activities were also determined in vitro. BSO treatment increased the partial clearance to acetaminophen glucuronide by 90% and 41% in young and old rats, respectively, and similarly, induced p-nitrophenol and 1-naphthol UDP-glucuronosyl transferase activities to a greater extent in young versus senescent animals. Thus, the induction of these UDP-glucuronosyl transferase activities by BSO is preserved in senescent animals. Although the partial clearance to acetaminophen sulfate was decreased in senescent control rats compared to young controls, BSO treatment decreased the in vivo rate of sulfation in both age groups. Similar to previous findings with the Sprague-Dawley strain, BSO treatment did not induce hepatic cytochrome P-450 content or activity or cytosolic p-nitrophenol sulfotransferase activity in young and senescent Fischer 344 rats. PMID- 1521596 TI - Learning performances and aging in cuttlefish (Sepia officinalis). AB - The use of an associative learning protocol with negative reinforcement allowed us to compare the performances of three groups of animals: young, middle-aged, and senescent. Statistical analysis of the results does not enable us to assert that a significant difference exists between the learning speeds of young and senescent animals. On the other hand however, the latter show poor scores in a retention test carried out 24 h after the learning session. These results suggest that the long-term memory processes are affected during the aging of these animals. PMID- 1521597 TI - Selection on stress resistance increases longevity in Drosophila melanogaster. AB - Tests for the causal involvement of specific physiological mechanisms in the control of aging require evidence that these mechanisms can be used to increase longevity or reproductive lifespan. Selection for later reproduction in Drosophila has been shown to lead to increased longevity, as well as increased resistance to starvation and desiccation stresses. Selection for increased resistance to starvation and desiccation in Drosophila melanogaster is here shown to lead to increased longevity, indicating that alleles that increase stress resistance also may increase longevity. The responses of desiccation and starvation resistance to selection are partly independent of each other, indicating a multiplicity of physiological mechanisms involved in selectively postponed aging, and thus aging in general. PMID- 1521598 TI - Increase of basic fibroblast growth factor immunoreactivity and its mRNA level in rat brain following transient forebrain ischemia. AB - We examined the time course of basic fibroblast growth factor (bFGF) immunoreactivity and its mRNA level mainly in the hippocampus after transient forebrain ischemia using immunohistochemistry, enzyme immunoassay (EIA), Western blot analysis and in situ hybridization. Neuronal death in the hippocampal CA1 subfield was observed 72 h after 20 min of ischemia. The number of bFGF immunoreactive(IR) cells increased 48 h-5 days after ischemia in all hippocampal regions. At 10 and 30 days, the bFGF-IR cells in the CA1 subfield had further increased in numbers and altered their morphology, enlarging and turning into typical reactive astrocytes with the advancing neuronal death in that area. In contrast, the number of bFGF-IR cells in other hippocampal regions had decreased 30 days after ischemia. The EIA study showed a drastic increase in bFGF levels in the hippocampus 48 h after ischemia (150% of that in normal rat) which was followed by further increases. In Western blot analysis, three immunoreactive bands whose molecular weights correspond to 18, 22 and 24 kDa were observed in normal rat and ischemia increased all their immunoreactivities. In the in situ hybridization study of the hippocampus, bFGF mRNA positive cells were observed in the CA1 subfield in which many bFGF-IR cells existed after ischemia. These data demonstrate that transient forebrain ischemia leads to an early and strong induction of bFGF synthesis in astrocytes, suggesting that the role of bFGF is related to the function of the reactive astrocytes which appear following brain injury. PMID- 1521599 TI - Differential cellular distribution of two sulphur-containing amino acids in rat cerebellum. An immunocytochemical investigation using antisera to taurine and homocysteic acid. AB - An antiserum to homocysteic acid was raised in rabbits. Immunogens were prepared by coupling this amino acid to bovine serum albumin by means of glutaraldehyde and paraformaldehyde. When applied to semithin or ultrathin sections of rat cerebellum, the antiserum produced selective labelling of glial cells and processes, including the Bergmann fibers. No enrichment of immunoreactivity was detected in nerve terminals of the major excitatory fiber systems. The distribution of homocysteic acid-like immunoreactivity was very different from that of taurine (another sulphur-containing amino acid), as judged from consecutive semithin sections labelled with a postembedding immunoperoxidase procedure and from ultrathin sections labelled with a postembedding double immunogold procedure. Taurine-like immunoreactivity was concentrated in Purkinje cells and was low in glial elements. Our data suggest that the cerebellum contains a glial pool of homocysteic acid (and/or precursors that may undergo spontaneous oxidation to homocysteic acid) and that this amino acid is unlikely to act as a cerebellar transmitter. PMID- 1521600 TI - Plasticity of binocular visual connections in the frog, Xenopus laevis: reversibility of effects of early visual deprivation. AB - In frogs, each lobe of the midbrain optic tectum receives two spatially aligned maps of binocular visual space, one through each eye. The map from the contralateral eye is the product of direct retinal input to the tectum, while that from the ipsilateral eye is mediated by a commissural system of connections that relays binocular visual information from one tectal lobe to the other. In Xenopus laevis, dark-reared from early life, the visuotectal map through the ipsilateral eye exhibits significant signs of disorder indicating that the normal development of the underlying "intertectal" system involves experience-dependent processes. Here we investigate the potential of this system for recovery from such deprivation-induced disruption. Three groups of animals were first dark reared from embryonic stages until 3 months, 12 months or 2 years after metamorphosis. These short-, medium- and long-term periods of visual deprivation are associated with a progressive disturbance of the intertectal system (Grant and Keating 1989b). The animals then experienced 12-18 months in a normal visual environment, before an electrophysiological mapping experiment was carried out to reveal the status of their intertectal system. Quantitative analyses of the visuotopic order in the ipsilateral visuotectal map and of its spatial alignment with the map derived from the contralateral eye revealed that these features were completely normal in all 3 experimental groups. It is concluded that defects present in the intertectal system of dark-reared Xenopus can be repaired by subsequent visual experience, and that the reparative capacity is not limited either by the animal's age or by the existing degree of prior disruption. PMID- 1521601 TI - Binocular interaction and disparity coding at the 17-18 border: contribution of the corpus callosum. AB - Binocular disparity, resulting from the projection of a three-dimensional object on the two spatially separated retinae, constitutes one of the fundamental cues for stereoscopic perception. The binocularity of cells in one hemisphere stems from two sources: i) from the ipsilateral ganglion cells in the temporal retina which converge with inputs coming from the contralateral nasal retina; the latter axons cross at the chiasma; ii) from inputs originating in the opposite hemisphere which cross in the corpus callosum. The objective of this study was to demonstrate that interactions from both types of inputs can result in the formation of disparity sensitive neurons and presumably that either type could mediate stereoperception based on disparity cues. Two types of disparity sensitive neurons were found in the normal cat: one type, showing maximal interactive effects around zero disparity responded with strong excitation or inhibition when the stimuli were in register. These neurons are presumed to signal stimuli situated about the fixation plane. The other type, also made up of two subtypes of opposed valencies, gave maximum responses at one set of disparities and inhibitory responses to the other set. These were presumed to signal stimuli situated in front of or behind the fixation plane. In the split chiasm cat, whose cortical binocularity is presumably assured by converging ipsilateral and callosal inputs, three of the four subtypes of disparity sensitive neurons were found, the uncrossed disparity cells being absent in these animals. Moreover, stimulating each eye individually indicated that nearly 80% of the cells in normal and about 40% in split-chiasm cats were binocularly driven. However, both these figures underestimated the amount of binocular interaction in the callosal recipient zone, since stimulating both eyes simultaneously showed that a proportionately larger number of cells were binocularly driven. Disparity sensitive cells also varied as a function of ocular dominance, i.e., cells signaling the fixation plane tended to have balanced dominance whereas units preferring stimuli situated in front of or behind the fixation plane were dominated by the ipsilateral and contralateral eyes, respectively. PMID- 1521602 TI - An improved graphical method for pattern recognition from spike trains of spontaneously active neurons. AB - Spontaneous activity and rhythmical oscillations are common features of large neuronal networks in mammals. Detection of repetitive spike patterns or pacemaker activity during electrophysiological recording of spontaneous action potentials from single neurons can be difficult if a "noisy" background is present. This paper describes an improved method for an online spike train analysis based on joint interval histograms (JIH, Rodiek et al. 1962). By means of higher ordered JIH the discrimination of spike patterns with repetitive bursting activity or oscillations is possible even when randomly distributed action potentials appear. Examples of simulated spike trains and those recorded from cultured hippocampal neurons are presented. PMID- 1521603 TI - Midbrain influences on ventrolateral medullo-spinal neurones in the rat. AB - A study has been carried out to investigate the influence of the periaqueductal grey matter (PAG) on spinally-projecting neurones in the rostral ventrolateral medulla (RVLM) in rats anaesthetised with urethane. Microinjection of D,L homocysteic acid was used to selectively activate nerve cell bodies in the PAG. Stimulation throughout the rostral half of the PAG and in the caudal PAG on a level with and dorsolateral to the level of the aqueduct evoked excitatory responses in 21 medullo-spinal cells in the RVLM. The neuronal excitation was associated with a rise in blood pressure. In contrast, stimulation within a restricted area of the ventrolateral PAG at the level of the dorsal raphe nucleus inhibited 10 medullo-spinal neurones in the RVLM, and produced variable changes in blood pressure. Convergence of excitatory and inhibitory influences from dorsolateral and ventrolateral stimulating sites in the PAG on to individual cells was also demonstrated. The results are discussed with respect to the role of the ventrolateral PAG in modulating the cardiovascular components of the "defence" response which is integrated by the dorsal PAG. PMID- 1521604 TI - Role of upper cervical inspiratory neurons studied by cross-correlation in the cat. AB - Axonal projections and synaptic connectivity of upper cervical inspiratory neurons (UCINs) were investigated in anaesthetised cats to clarify their role as propriospinal respiratory interneurons. Antidromic mapping showed axonal collaterals near phrenic and intercostal motonuclei. Of the UCINs tested, 37% had collaterals at T3-4; 55% had ipsilateral projections and 45% had contralateral projections. Ipsilateral or contralateral cross-correlations of the activity of pairs of UCINs (one on each side of the spinal cord) with the discharge of internal intercostal, external intercostal (T3-4) or phrenic nerves revealed similar features. Those with the internal intercostal and phrenic nerves were interpreted as evidence for shared or oligosynaptic excitation, those with the external intercostal nerve as shared excitation and inhibition. No evidence for monosynaptic connections was found. Monosynaptic connections could also not be demonstrated between inspiratory intercostal neurons located near (less than 0.5 mm) the UCINs collateral arborizations in T3-4, examined by cross-correlation. Afferent feedback from internal intercostal nerves (T3-4) was investigated by cross-correlating nerve stimulation with UCINs activity. Ipsilateral and contralateral cross-correlograms had similar features, providing evidence for excitation in some cases and inhibition in others. Finally, cross-correlations between ipsilateral UCINs and cervical sympathetic nerves were featureless. The results suggest that the role of UCINs as part of a respiratory propriospinal control system analogous to forelimb motor control is untenable, although they may be part of an intercostal afferent feedback loop. PMID- 1521605 TI - Nucleus basalis lesions in neonate rats induce a selective cortical cholinergic hypofunction and cognitive deficits during adulthood. AB - Ibotenic acid was infused into the nucleus basalis magnocellularis (nBM) of 2-day old rats to eliminate immature cholinergic neurons before they develop functional synaptic connections in the neocortex. For bilaterally lesioned neonates, cognitive testing was initiated 2 months after lesioning and animals were sacrificed at 8 or 12 months of age. Lesioned animals exhibited a marked deficit in the retention of passive avoidance behavior, as well as in the acquisition of 2-way active avoidance behavior. Lesioned animals also made significantly more alternation errors than control animals in the Lashley III spatial maze and showed severe impairments in general learning, reference memory and working memory during 17-arm radial maze testing. For all 4 tasks, neonatally lesioned animals did not show any recovery to the performance level of control animals. Histological analysis of the subcortex from lesioned animals during adulthood revealed: (1) a substantial reduction in acetylcholinesterase-positive cells (presumably cholinergic) within the nucleus basalis, (2) decreased acetylcholinesterase staining in neocortex and (3) a gliosis essentially restricted to the globus pallidus. Surrounding brain regions were apparently not damaged as a direct result of excitotoxin infusion. Neurochemically, neonate nBM lesioning produced a long term cholinergic hypofunction as evidenced by significant reductions of 25% and 18% in frontal cortex choline acetyltransferase (CAT) activity at 12 and 8 months of age, respectively. By contrast, prefrontal cortical concentrations of biogenic amines and their metabolites were unaffected, thus indicating a degree of neurochemical specificity for these neonatal nBM lesions. The persistent cortical cholinergic hypofunction in lesioned animals may be related to the long term deficits in learning/memory abilities that were also observed. It is suggested that neonatal nBM lesioning could provide a useful animal model for elucidating the plasticity of the developing brain after cortical anervation. PMID- 1521606 TI - Human ocular torsion during parabolic flights: an analysis with scleral search coil. AB - Rotation of the eyes about the visual axis is known as ocular torsion. A lateral inclination (a "roll") of the head induces ocular torsion in the opposite direction, a response known as ocular counterrolling. For six subjects, we recorded the static (head still) and dynamic (head in oscillatory roll motion) ocular torsion in normal 1 g condition and also during the microgravity and hypergravity periods of parabolic flight, using the electromagnetic scleral search coil technique. With the head still, the direction and magnitude of torsion that occurred in response to microgravity and hypergravity differed substantially from one individual to another, but there was a significant difference in torsional magnitude between the microgravity and hypergravity periods, for all static head positions including the upright position. Under normal 1 g conditions, counterrolling compensated for about 16% of (voluntary) static head roll, while dynamic counterroll was much larger, up to 36% of head roll at 0.55 Hz. With increasing frequency of head oscillation between 0.33 Hz and 0.55 Hz, the gain of counterrolling increased and there was no change in the phase relationship. The gain of dynamic counterroll (in response to voluntary head rolling) was not significantly less in hypogravity, suggesting that on the ground at these frequencies the contribution of gravity and gravity receptors to this reflex is redundant: this reflex is probably driven by the semicircular canals. In some subjects, the torsional displacement in microgravity is accompanied by micro-torsional oscillatory motion. PMID- 1521607 TI - Effect of knee joint laxity on long-loop postural reflexes: evidence for a human capsular-hamstring reflex. AB - The onset latency and discharge amplitude of preprogrammed postural responses were evaluated in order to determine if the structure of synergistic activation could be altered by ligamentous laxity at the knee joint. Twelve subjects with unilateral and one subject with bilateral anterior cruciate ligament (ACL) insufficiency were tested while standing on a moveable platform. External balance perturbations (6 cm anterior or posterior horizontal displacements of the platform) were presented at velocities ranging from 15 to 35 cm/s. Perturbations were presented under the following experimental conditions: unilateral and bilateral stance, knees fully straight or flexed, and with ankle motion restricted or free. These stance, knee position, and ankle motion conditions were introduced to alter the stress transmitted to the knee joint during movement of the support surface. The automatic postural response was recorded from the tibialis anterior (T), quadriceps (Q), and medial hamstrings muscles (H) bilaterally. The normal response to an externally induced backward sway involved the automatic activation of T and Q at latencies of 80 ms and 90 ms respectively. Activation of the hamstrings in the non-injured extremity was not coupled with the postural response. Hamstrings are not typically involved in the correction posterior sway because H activation would tend to pull the center of mass further backwards. However, when the response in the ACL-deficient extremity was compared to the non-injured limb: (1) the automatic postural response in the ACL-deficient extremity was restructured to include hamstrings activation (100 ms latency), (2) H activation time was faster and less variable in the ACL-deficient limb, and (3) the ratio of H/Q discharge amplitude integrated over 100 ms and 200 ms from the onset of EMG activation showed a dominance of hamstring activity during unilateral stance on the lax limb. In addition, H/Q ratios integrated over 200 ms showed dominant hamstring activity in the ACL-deficient limb during bilateral stance. (4) Cross-limb comparisons showed greater normalized IEMG amplitudes for T, H, and Q during unilateral stance on the lax limb. These results suggest that a capsular-hamstring reflex is integrated into the existing structure of a preprogrammed postural synergy in order to compensate for ligamentous laxity. Furthermore, the generalized increase of response gain observed during perturbations of unilateral stance on the lax limb indicates that joint afference can modulate central programming to control localized joint hypermobility. A concept of postural control is discussed with respect to the capsular reflex, joint loading and displacement of the center of gravity. PMID- 1521608 TI - Inhibitory effects on flexor reflexes in patients with a complete spinal cord lesion. AB - The inhibitory effects on flexors of electrical stimulation of a distal peripheral nerve were investigated in 7 paraplegic patients having a complete spinal cord section. The stimuli (3-50 mA) were applied to the sural nerve. Their effects were investigated on: 1) the ipsi- and contralateral H reflex of the Tibialis Anterior (TA); 2) the continuous EMG activity reflexly elicited in TA by a sustained pinch of the foot and 3) on the reflexes evoked in TA by contralateral sural nerve stimulation. Sural nerve stimulation induced two peaks of facilitation of the ipsilateral TA H reflex that could be replaced by inhibition as the stimulus intensity was increased. The comparison of the effect on H reflexes and the EMG activity suggests presynaptic inhibition of Ia fibres at time intervals longer than 300 ms. The stimulation could depress the sustained EMG reflex activity and induce a period of silence whose duration increased with the intensity of the stimulation. As shown in a previous study, a sural nerve stimulation induced a reflex in TA with a prolonged (more than 130 ms) latency. This late reflex could be selectively inhibited by a contralateral sural nerve stimulation, probably at an interneuronal level. These results confirm that the late reflex in TA is similar to the one observed after Flexor Reflex Afferent (FRA) stimulation in the acute spinal cat with DOPA. In addition, they show that at least some part of the "half centre" organization which has been described in the acute spinal cat with DOPA is also present in the human spinal cord chronically deprived of supraspinal control. PMID- 1521609 TI - Motor control prior to movement onset: preparatory mechanisms for pointing at visual targets. AB - The present study investigated the mechanisms involved in the preparation of pointing movements in humans. We provided visual precues on the location of the upcoming target, and registered the effect of these precues on the reaction time (RT = interval between target appearance and movement onset). Generally, precues were found to reduce RT, suggesting that some aspects of the preparatory process have been advanced in time. In Exp. 1, precues fully specified the direction required for the upcoming movement while indicating only a range of movement amplitudes; in Exp. 2, precues fully specified the amplitude and indicated a range of directions. In both experiments, RT was shorter than in control trials without precues, and gradually increased with the size of the precued amplitude or direction range. This result suggests that the preparation of either parameter is possible without knowing the precise value of the other, i.e. amplitude and direction are not prepared in a fixed order. Furthermore, our results are consistent with the view that movement preparation includes a progressive contraction of the precued range towards the final value. The speed of this process can be estimated as 0.31 cm/ms for amplitude, and 1.7 deg/ms for direction ranges. In Exp. 3 and 4, precues indicated both amplitude and direction as ranges only. The size of the amplitude range was held constant while the size of the direction range was varied (Exp. 3), or vice versa (Exp. 4). Under these conditions, RT increased with the size of the varied range.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1521610 TI - Firing relations of medial entorhinal neurons to the hippocampal theta rhythm in urethane anesthetized and walking rats. AB - The firing of neurons from layers II and III of medial entorhinal cortex (MEC) was examined in relation to the hippocampal theta rhythm in urethane anesthetized and walking rats. 1) MEC neurons showed a significant phase relation to the hippocampal theta rhythm in both walking and urethane anesthetized rats, suggesting that this region contributes to the generation of both atropine resistant and atropine-sensitive theta rhythm components. 2) The proportion of phase-locked cells was three times greater in walking rats (22/23 cells) as compared to anesthetized rats (8/23 cells), indicating that MEC cells made a greater contribution during walking theta rhythm. This difference was also manifest in the greater mean vector length for the group of phase-locked MEC cells during walking: 0.39 +/- 0.13 versus 0.21 +/- 0.08. Firing rate differences between walking and urethane conditions were not significant. 3) In walking rats, MEC cells fired on the positive peak of the dentate theta rhythm (group mean phase = 5 degrees; 0 degrees = positive peak at the hippocampal fissure). This is close to the reported phases for dentate granule and hippocampal pyramidal cells. The distribution of MEC cell phases in urethane anesthetized rats was broader (group mean phase = 90 degrees), consistent with the phase data reported for hippocampal projection cells. These findings suggest that medial entorhinal neurons are the principal determinant of theta-related firing of hippocampal neurons and that their robust rhythmicity in walking as compared to urethane anesthesia accounts for EEG differences across the two conditions. PMID- 1521611 TI - The effects of wrist muscle vibration on human voluntary elbow flexion-extension movements. AB - The effect of forearm muscle tendon vibration during alternating step flexion extension movements about the elbow was studied in normal humans. In one experiment, a vibrator was mounted over either the forearm flexor or the extensor muscle. In a second experiment, a vibrator was mounted over either the forearm muscle or the biceps muscle. In both experiments, vibration was applied either to a single muscle or simultaneously to both muscles during elbow flexion-extension movements. After a period of practice, subjects learned the required movements and were able to make them with their eyes closed. Application of vibration to the forearm and the biceps muscle during extension movements produced an undershoot of the required end-movement position. Moreover, application of high frequency vibration (100 Hz) to the forearm extensor and flexor muscle produced an overshoot of the required end-movement position. The observed results are consistent with vibration induced activation of muscle spindle receptors not only in the lengthening muscle during movement but also in the forearm muscles. It is suggested that the pattern of distribution of muscle spindle afferent from the forearm muscle onto alpha-motoneurons of muscles acting at the elbow has played an important role of alternating step flexion-extension movements. PMID- 1521612 TI - Memory-guided saccades: what is memorized? AB - In order to find out whether extraretinal (oculomotor, internal) input suffices to provide the oculomotor system with the information necessary for saccadic control, two subjects were asked to make memory-guided saccades in complete darkness, after three different location acquisition conditions. These conditions were visually-guided saccades (SA), providing retinal (external) and extraretinal input, visual peripheral target presentation during central target fixation (FI) (external input only), and smooth pursuit (PU) (internal input only). Either 2 or 12 s (delay) after locating the target, the subjects had to make a memory-guided saccade toward it in complete darkness. The results show that whereas these memory-guided saccades were quite accurate for trials with preceding external input, this was not the case with acquisition through internal input alone. Moreover, the accuracy of memory-guided saccades decreased when the delay increased from 2 to 12 s for both conditions with retinal input, whereas the accuracy increased for the one condition without retinal input, i.e., the smooth pursuit location acquisition. Furthermore, when both retinal and oculomotor inputs were provided, better accuracy of the memory-guided saccades was observed than with single input. PMID- 1521613 TI - The development of corticospinal projections to tail and hindlimb motoneurons studied in infant macaques using magnetic brain stimulation. AB - The EMG responses evoked in tail, leg and foot muscles by magnetic stimulation (MS) of the brain were investigated in two male macaque monkeys under ketamine sedation. The animals were studied longitudinally over a period of 7 months (from 2.75 to 9.75 months old). MS was generally ineffective in eliciting responses when the animals were 2.75-4.5 months old, even at maximum stimulator output (1.5 Tesla). After this time the threshold for evoking EMG responses decreased considerably, and there was an increase in the probability of occurrence of the responses. These age-related changes plateaued at about 7.5 months, after which they remained fairly constant at adult levels. In both animals the maturation of these responses in tail and hindlimb muscles occurred later than in forelimb muscles. PMID- 1521614 TI - Control of arm movement after bilateral lesions of area 5 in the monkey (Macaca mulatta). AB - The effect of bilateral area 5 lesions on the analysis of proprioceptive information and the guidance of reaching movements was studied in three rhesus monkeys. In the first paradigm (Proprioceptive discrimination test) the monkeys were trained to discriminate between movements of a joystick to the right or left without visual control; they reported the direction of movement by touching or not touching a screen (go/no-go task). After area 5 had been removed, the monkeys were only mildly impaired on this test. It is concluded that such simple joint movement could be analysed in area 2, area 5 being concerned with more complex arm movements. In the second paradigm (Searching test) the monkey had to find a peanut on a board in the dark using proprioceptive information stored in memory during previous trials. After area 5 lesions, the number of correct reaches was not modified but the number of errors after an incorrect trial (correcting movement) was significantly increased. The data suggests that when visual input is not available, area 5 is involved in the guidance of arm movements on the basis of proprioceptive inputs. PMID- 1521616 TI - Spatiotemporal characteristics of direction-selective neurons in the middle temporal visual area of the macaque monkeys. AB - In an attempt to elucidate the mechanisms of directional selectivity in the neurons of the middle temporal visual area (MT) of macaque monkeys, we presented small numbers of sequentially flashed stimuli with various temporal and spatial intervals within the receptive field (RF) of direction-selective MT neurons. Experiments were performed using awake macaque monkeys trained to fixate on a set of short stationary lines. Stimuli were presented on a CRT screen under computer control. In two-flash experiments, responses to a test flash presented in the center of the RF were examined following a conditioning flash presented in various locations within the RF. Inhibition in the null direction was observed in about 78% of MT neurons, while facilitation was relatively weak in this group of neurons. In most of these neurons, the ranges of temporal and spatial intervals that produced directional selectivity in two-flash experiments were within half the values and double the values, respectively of those in multi-flash experiments. In the remaining 22% of direction-selective MT neurons, several flashed stimuli were necessary to produce directional selectivity. Most of these neurons showed facilitation in the preferred direction. It appears that the inhibitory mechanisms in the null direction are sufficiently strong to be induced by a single conditioning flash whereas the facilitatory mechanisms are weaker and several stimuli are required for production of the direction-selective response. PMID- 1521615 TI - The currents that flow in the somatosensory cortex during the direct cortical response. AB - A current-flow and current-source-density analysis of the sensory evoked response (SER) and the direct cortical response (DCR) in the somatosensory cortex of rats was performed to determine the origin of these potentials. The SER was found to originate in layers II and III, as in cats, with a single excitatory neuronal circuit component. The DCR, on the other hand, has five components, three inhibitory and two excitatory. The activation and magnitude of these components vary with stimulus strength and frequency. During the second and fourth ms of the response, two inhibitory currents flow in layers V and VI; 2 ms later, excitatory current flows in layers II and III. This excitatory current appears to be the same one involved in the SER. Five ms later, the superficial excitatory current is replaced by an inhibitory one in the neighborhood of the DCR's negative peak. At strong stimulus strengths, this is followed by an excitatory current in layer V. The early inhibitory and excitatory components step up through layers upper VI, V and III over time, implying that inhibition followed by excitation moves upward through cortex. The currents associated with the DCR in somatosensory cortex are compared with those for the DCR in motor and association cortex. PMID- 1521617 TI - The pretectal cholinergic system is involved through two opposite ways in frog monocular OKN asymmetry. AB - Frog monocular horizontal optokinetic nystagmus (OKN) has been studied by coil recordings, before and after unilateral microinjection of cholinergic drugs into the pretectum. The recorded eye was either contralateral or ipsilateral to the injected structure. Before injection, monocular OKN displayed a directional asymmetry, reacting only to stimulations in the temporonasal (T-N) direction. The intrapretectal administration of a cholinergic muscarinic agonist (oxotremorine), as well as that of a nicotinic antagonist (D-tubocurarine), abolished the monocular OKN asymmetry, inducing the appearance of the naso-temporal (N-T) component; the difference between the slow phase velocity gain of both components was no longer significant. These data suggest that acetylcholine (ACh), at the level of the pretectum, acts in opposite ways through muscarinic and nicotinic binding sites; monocular OKN asymmetry could result, at least partially, from a facilitating nicotinic effect and an inhibitory muscarinic effect. Possible interactions with other transmitter systems are discussed. PMID- 1521618 TI - Orienting behavior in hamsters with lesions of superior colliculus, pretectum, and visual cortex. AB - We examined cortical and subcortical mediation of visual locomotor orienting function by comparing the behavior of hamsters with discrete bilateral lesions affecting the pretectum, superior colliculus (SC), or visual cortex (VC). Orienting and approach to stationary targets was evaluated by measuring the accuracy of hamsters' approaches to small black apertures, located at eye level along the wall of a circular white arena. Hamsters with bilateral ablation of the visual cortex were slightly impaired for approaches to central field targets, whereas those with ibotenic acid lesions of the pretectum (which spares fibers of passage and thus leaves tectal afferents intact) were totally unimpaired. Hamsters with transection of the brachium of SC (BSC) at the prectectal-SC (PT SC) border were severely impaired in their ability to approach stationary targets in central and peripheral fields. Thus, we did not detect any of the central field sparing that has been reported by others for rodents with similar lesions. Several possible reasons for the disparity between our results and those of others are discussed. Overall, our results indicate that in hamsters the SC is essential for normal visually guided approach to dark, stationary targets throughout the visual field. Further, our results and qualitative observations indicate that the approach errors are most likely due to deficits of visuomotor integration rather than to a lack of visual scanning. PMID- 1521619 TI - Aberrant retinal projections to midbrain targets mediate spared visual orienting function in hamsters with neonatal lesions of superior colliculus. AB - Rodents, cats, and most nonmammalian vertebrates with bilateral tectal deafferentation or ablation in adulthood are extremely deficient at orienting to visual stimuli; yet animals with neonatal lesions of superficial layers of the superior colliculus (SC) show partial sparing of this response, particularly for targets in the central visual field. In this study, we sought to determine whether these spared orienting abilities are mediated by aberrant retinal projections to the remaining intermediate layers of the SC, or whether visual cortex (VC) mechanisms or alternative behavioral strategies are responsible. Neonatal golden hamsters received either bilateral heat lesions of the SC (rlSC), or a heat lesion of the right SC and enucleation of the right eye (rSCrE). This latter procedure causes axons from the left eye to recross the tectal midline and terminate in the "wrong" (left) SC (Schneider 1973). As adults, both groups of hamsters were extremely deficient in visually guided approach to stationary targets, although rlSC-lesioned hamsters showed some sparing for central field targets and rSCrE-lesioned hamsters often made wrong-direction turns for targets in the left peripheral field. We then subjected both groups of neonatally lesioned hamsters to bilateral aspiration lesions of the VC. Retesting showed no change in visual orienting behavior as a result of the cortical lesions. Labeling of the optic tract with horseradish peroxidase (HRP) revealed abundant aberrant retinal projections to remaining intermediate layers of the SC and thalamic nucleus lateralis posterior (LP), as well as supernormal innervation of pretectal nuclei, the dorsal terminal nucleus of the accessory optic tract, and the ventral nucleus of the lateral geniculate body (LGv). We conclude that the spared visual orienting capabilities of hamsters with rlSC and rSCrE lesions are mediated by the aberrant midbrain projections, and that cortical mechanisms are not involved in spared visual orienting functions following these neonatal lesions. PMID- 1521620 TI - Malignant melanoma of the mucous membranes. AB - Primary malignant melanoma occurring in mucous membranes is uncommon. Of 410 patients with malignant melanoma, 14 (3.4%) had their primary tumour located in mucosal membranes. Five of the tumours were in the mucosal lining of the head and neck, five in the gastrointestinal tract mucosa and four in the female genitalia. Eight of the tumours were ulcerated, necrotic and deeply invasive. The most common histological subtype was acral lentiginous melanoma. Surgical resection of the primary tumour was performed in 10 patients. In the other four, surgery was not feasible, and they were treated by irradiation and immunotherapy. Six patients underwent regional lymph node dissection. In four of them, regional metastases were found. Chemotherapy was given to seven patients for widespread metastases. Nine patients (64%) died of metastatic melanoma within 2 years. The remaining five patients are alive after 3 to 8 years. It appears that mucosal membrane melanoma is a distinct variant of the disease due to both its aggressive biological behaviour and its relative inaccessibility for surgical removal, and may therefore be classified separately. PMID- 1521621 TI - Primary non-Hodgkin's lymphoma of the thyroid. AB - Eighty seven cases of primary non-Hodgkin's lymphoma of the thyroid presenting to the Beatson Oncology Centre were reviewed. Stage IE and Stage IIE disease accounted for 79 of 87 cases. In a univariate analysis the presence of dysphagia, dyspnoea, positive nodes, stage or male sex all had a statistically significant detrimental influence on survival. Stage and dysphagia were the most influential individually and a multivariate analysis indicated that the prognostic information in all these features was essentially captured by just these two. A prognostic scoring index based upon stage of disease and the presence of dysphagia has been developed. Overall 5 year survival was 43%. Five year survival for Stage IE patients without symptoms of compression was 74%. Patients who underwent surgical resection of tumour followed by local irradiation appeared to survive longer than patients managed by irradiation without surgery, although after adjustment for prognostic features this advantage was not statistically significant. PMID- 1521622 TI - Radical breast surgery with a contact Nd:YAG laser scalpel. AB - The use of a contact Nd:YAG laser scalpel during radical and modified radical mastectomy was evaluated in 18 patients with carcinoma of the breast. The laser scalpel performed well as a haemostatic tool, the associated mean blood loss for modified radical mastectomy being 132 ml. Operating time, operative blood loss, laser energy required and postoperative wound drainage were all related to patient obesity, correlating significantly with body weight and/or breast weight. The incidence of axillary seroma was not reduced by laser surgery and occurred in 53% of patients undergoing modified radical mastectomy. The Nd:YAG laser scalpel is an excellent haemostatic tool but it does not appear to have any other advantages over conventional surgery for mastectomy. PMID- 1521623 TI - Psychological morbidity in the first year after breast surgery. AB - In this prospective study, the psychological morbidity associated with the treatment of breast cancer was assessed. The study population comprised all patients referred to one centre with a recently diagnosed breast lump, who were to undergo surgery. Psychological morbidity was assessed preoperatively and at 6 and 12 months postoperatively by modified Rotterdam Symptom Checklist. Three hundred and twenty patients completed all three questionnaires: 93 women undergoing mastectomy, 73 women having conservation therapy for breast cancer and 156 women having biopsy for benign breast disease. Patients with a breast malignancy smaller than 4 cm in diameter were treated by lumpectomy and radiotherapy, anti-oestrogen therapy or chemotherapy alone or in combination. Psychological morbidity among patients with malignant disease was significantly greater than that seen in the group with benign disease. Among cancer patients, a significant decrease in anxiety and depression occurred during the year following surgery. The study failed to demonstrate any psychological advantage associated with breast conservation. PMID- 1521624 TI - An analysis of the diagnostic accuracy of endoscopic biopsy and cytology in the detection of oesophageal malignancy. AB - The role of combined cytohistological examination in the differentiation of benign from malignant oesophageal mucosal lesions was studied in 331 patients. Malignancy was confirmed by specimen histopathology in 58 patients. Both endoscopic biopsy and cytology were positive in 41 (71%) patients. Endoscopic biopsy alone suggested malignancy in 10 cases (17%) while cytology was positive after negative biopsy in seven (12%). Cytology yielded four false positive and 10 false negative results giving a sensitivity level of 81%, a specificity of 98% and a positive predictive value for oesophageal malignancy of 92%. Histology on the other hand yielded one false positive and seven false negative results providing a sensitivity of 87%, a specificity of 99% and a positive predictive value of 96%. No patients were left undiagnosed using both diagnostic modalities; cytology increased the diagnostic yield from 87% to 100%. Exfoliative cytology was most valuable in the diagnosis of tumours of the lower one-third of the oesophagus where seven of 31 malignancies (23%) were identified by this method alone (P less than 0.05). Neither the histological type of the tumour nor the morphological appearance was found significantly to affect the diagnostic yield (P greater than 0.05). We conclude that cytological examination should be standard practice in the investigation of oesophageal lesions. PMID- 1521625 TI - Temporary transection of the trachea in cervical esophagectomy. AB - A new method to preserve the larynx and to achieve a better exposure of the cervical esophagus was performed in four patients with cervical esophageal carcinoma. The trachea, which prevented exposure of the esophagus, was cut, keeping the continuity of the recurrent laryngeal nerves. The tracheo-esophageal space was opened like a double door. The cervical esophagus was replaced with a substitution followed by tracheal reconnection. Three different substitutions were used for the reconstruction of the cervical esophagus: free jejunum, free skin tube graft and stomach. This procedure offers a further excision of the esophagus while preserving the larynx, and results in free surgical margins and safe anastomoses of the alimentary tract. This method is applicable for a curative operation of carcinoma without invasion to the trachea to offer the patient a better quality of life. PMID- 1521626 TI - Increasing incidence of adenocarcinoma of the proximal stomach. AB - A retrospective study was performed on patients with histologically proven gastric adenocarcinoma during the periods 1972 to 1976 (n = 368) and 1986 to 1990 (n = 870) to analyse the potential changes in tumour distribution within the stomach. A recent increase in gastric cancer patients admitted to our institution represents a change in the referral patterns of the patients. The mean age and male:female ratio according to site distribution of the tumour were not found to differ between the two periods. The proportion of carcinomas of the upper third of the stomach was, however, significantly increased (P less than 10(-6)) in the recent series (36.4%) compared with the old series (20.6%). Since the incidence of gastric cancer in our population seems to be unchanged, this may suggest a true increase in proximal gastric tumours. The data may indicate possible changes in aetiological influences. PMID- 1521627 TI - The impact of intraoperative ultrasonography of the liver on the surgical strategy of patients with gastrointestinal malignancies and hepatic metastases. AB - Intraoperative ultrasonography (IOUS) of the liver is a very useful tool during surgery for gastrointestinal tumors or hepatic tumors. In a prospective study of 82 elective operations for 57 gastrointestinal tumors and 25 hepatic tumors or metastases, we compared IOUS with preoperative ultrasonography, CT-scanning and MRI. IOUS supplied additional information in 38% of the operations. In 22% of the cases, this had a major impact on the intraoperative strategy with an alteration of the procedure. IOUS has a higher detection rate of intrahepatic lesions, discriminates better between solid or cystic nature of the tumor and offers the possibility of performing a safe and radical hepatic resection by its ability to localize lesions in relation to vascular structures. IOUS is a safe and simple technique which will be more cost-effective than extensive preoperative evaluation of the liver. It provides a more complete clinical staging of patients for whom adjuvant therapy is considered after resection of a colorectal carcinoma. PMID- 1521628 TI - The effect of portal venous flow on the washout of a regionally injected marker substance 99mTc-methylene diphosphonate after hepatic arterial blockade with degradable starch microspheres. AB - Patients with hepatic metastases derived from colorectal carcinoma have a poor prognosis. Regional chemotherapy, either alone, or combined with agents such as degradable starch microspheres (DSM) that reduce or abolish intrahepatic arterial flow and potentiate the delivery of cytotoxics to hepatic metastases, have not significantly improved survival. We have investigated one positive mechanism, namely the effect of portal venous washout of cytotoxics, for the poor efficacy of drugs administered either alone or in combination with DSM via the hepatic artery in the rat. Using a radiolabelled marker, 99mTc-methylene diphosphonate (MDP), to represent a cytotoxic drug, the initial studies indicated that with the hepatic artery and portal vein clamped, a volume of 0.05 ml of the marker administered via the hepatic artery resulted in the most uniform intrahepatic distribution with minimal washout into the systemic circulation (21 +/- 3.7%). When the hepatic artery was clamped, the washout of MDP was reduced from 100% (with clamps on the portal vein and hepatic artery) to 84.2 +/- 7.7%. DSM administered concomitantly with MDP, resulted in a greater reduction of the portal venous washout of the marker (63 +/- 2.4%). Administration of DSM and MDP via the hepatic artery and with the portal vein clamped further reduced the washout of the marker to (21 +/- 2.26), results similar to those observed with inflow vessel clamps. Following restoration of portal venous flow, there was a rapid washout of 53.7 +/- 7.6% of the marker into the systemic circulation. The results of this study suggest that portal venous washout of regionally delivered cytotoxics, either alone or in combination with DSM, offer an explanation for the poor efficacy of regional chemotherapy in improving the prognosis of patients with hepatic metastases. PMID- 1521629 TI - Iodostearic acid in the treatment of advanced gastrointestinal carcinoma. AB - This phase II non-comparative trial evaluated the efficacy of intramuscular iodostearic acid in the treatment of 30 patients with advanced carcinoma of the gastrointestinal tract. These included 17 patients with colorectal carcinoma, seven with pancreatic carcinoma, four with gastric carcinoma, one with hepatocellular carcinoma and one with cholangiocarcinoma. Iodostearic acid emulsion (2 ml/1.2 g) followed by depomedrone (0.5 ml/10 mg) was injected intramuscularly twice weekly. No serious toxic effects were observed, the main side effects being local pain at the injection site and hot flushes. There were no partial or complete responses. Stable disease was seen in six of 30 patients (20%) at 3 months and three of 30 patients (10%) at 6 months. In conclusion, intramuscular iodostearic acid is relatively non-toxic, however, it appears to be of little value in the treatment of patients with advanced gastrointestinal carcinomas. PMID- 1521630 TI - Local excision of rectal cancer: report of a technique and results. AB - A technique for the local treatment of rectal cancer was performed in 29 patients who satisfied the criteria for local treatment. Four patients were classified as Dukes' stage A and 25 were stage B. Local treatment was performed by either direct excision or anorectal mobilization. The former was carried out in 13 patients in whom the tumor was located less than 7 cm from the dentate line. Excision after anorectal mobilization was performed in 16 patients with tumors located more than 7 cm from the dentate line. Patients were followed up for 5 to 10 years. They had normal rectal function after operation with normalization of rectal pressure and myoelectric activity of sphincteric muscles. Twenty four patients are alive and tumor-free. The five failures were Dukes' B category; four (30%) treated by direct excision and one (6%) by anorectal mobilization. They were subjected to a second, combined excision operation of the rectum: two patients died of distant metastasis and three are alive and tumor-free. The study showed that 12% of Dukes' B category patients had preoperative nodal deposits which escaped detection. Direct excision, owing to its high incidence of recurrence, should be restricted to Dukes' A category tumors, when the upper tumor edge is less than 7 cm from the dentate line. Otherwise, and with all Dukes' B category tumors, the anorectal mobilization operation is preferable. PMID- 1521631 TI - Intra-luminal tumour cells and peri-anastomotic tumour growth in experimental colonic surgery. AB - Most loco-regional tumour recurrences following colorectal cancer surgery are extra-luminal. This study was designed to determine the conditions necessary for viable intra-luminal tumour cells to give rise to extra-luminal tumour growth in an experimental animal model. When carcinoma cells were injected into the colonic lumen in the absence of a colonic wound, tumour growth was rare (1 of 24 animals). However, when tumour cells were injected intra-luminally either in the presence of an apparently watertight colotomy repair or prior to the transmural insertion of interrupted sutures, peri-anastomotic +/- widespread peritoneal tumour growth was consistently observed. Tumour growth did not occur on the mucosa of the bowel. These findings suggest that viable intra-luminal tumour cells can migrate across a clinically intact experimental large bowel anastomosis or along transmural suture tracts to give rise to extra-luminal tumour growth. PMID- 1521632 TI - Crypt cell carcinoma of the appendix. AB - A case of crypt cell carcinoma of the appendix is reported detailing its characteristic histological and immunohistochemical features and outlining current view on management. PMID- 1521633 TI - Leiomyosarcoma of the chest wall following treatment of Hodgkin's disease. AB - This case report describes the development of a leiomyosarcoma in the chest wall of a patient previously treated for Hodgkin's disease. Although a similar case has not been reported previously, we managed our patient with wide local excision. PMID- 1521634 TI - Dermal angiosarcoma of the breast: a complication of primary radiotherapy? AB - A 70-year-old female developed recurrent disease following radiotherapy for primary inoperable breast cancer 5.5 years previously. Salvage mastectomy was performed. Pathology revealed recurrent breast cancer, along with a second primary malignancy, a dermal angiosarcoma. Radical excision of recurrent angiosarcoma failed. Irradiation combined with hyperthermia showed good palliation. The angiosarcoma's possible relation to the initial radiotherapy is discussed. PMID- 1521635 TI - Primary cystadenomatous tumors of the bile ducts. AB - Two cases of cystadenomatous tumors of the biliary tract are presented. One was a cystadenoma and the other one was a cystadenocarcinoma. They are rare tumors, difficult to diagnose accurately preoperatively. The differential diagnosis of the cystic tumors of the liver in countries with a high incidence of liver hydatid disease is very important. PMID- 1521636 TI - The association of breast cancer in patients with melanoma. PMID- 1521637 TI - Breast reconstruction using latissimus dorsi island flap without an endoprosthesis. PMID- 1521638 TI - Tests of human sperm function and fertilization in vitro. AB - OBJECTIVE: To review recent studies on the development of new tests of human sperm function and evaluation of which sperm characteristics are most important for fertilization in vitro by logistic regression analysis. STUDY SELECTION: Recent studies on the relationship between putative and new tests of human sperm function and fertility in vitro or in vivo are discussed in this review. Some physiological and technical aspects are included. MAIN OUTCOME MEASURES: Fertilization rates in vitro and sperm tests including standard semen analysis, improved morphology assessment, objective assessment of sperm motility and movement characteristics, nuclear maturity, hypo-osmotic swelling, the acrosome and the acrosome reaction, acrosin activity, human sperm-hamster oocyte penetration assay, and sperm-zona pellucida (ZP) and sperm-oolemma binding. RESULTS: The percentages of sperm with normal morphology and a normal intact acrosome, mean linearity, and the number of sperm binding to the ZP were highly significant related to fertilization rates in vitro. Other sperm tests evaluated usually provided no additional information about fertilization rates. The human ZP is highly selective for binding of morphologically normal sperm. Acrosome reacted human sperm have little or no ability to bind to the ZP. CONCLUSION: Results of in vitro fertilization can be used to evaluate tests of human sperm function. Logistic regression analysis is a powerful method for determining which groups of sperm characteristics are independently related to fertilization rates. Normal morphology, linearity, acrosome status, and sperm-ZP binding are the most important characteristics for fertilization in vitro. PMID- 1521639 TI - TES and Tris (TEST)-yolk buffer systems, sperm function testing, and in vitro fertilization. PMID- 1521640 TI - Body weight, hyperinsulinemia, and gonadotropin levels in the polycystic ovarian syndrome: evidence of two distinct populations. AB - OBJECTIVE: To investigate the impact of body weight (BW) and insulin levels on gonadotropin and androgen levels in women with the polycystic ovarian syndrome (PCOS). DESIGN: Comparative study of endocrinologic parameters in PCOS women. SETTING: University Hospital Reproductive Endocrinology Unit. PATIENTS: Thirty obese and 19 nonobese women with PCOS. Seven obese and 7 nonobese normal women. MAIN OUTCOME MEASURES: Serum concentrations of insulin, testosterone, androstenedione, luteinizing hormone (LH), follicle-stimulating hormone. Serum LH response to gonadotropin-releasing hormone (GnRH) administration and assessment of insulin resistance by the continuous infusion of glucose with model assessment (CIGMA) test. RESULTS: Fasting insulin levels correlated with body mass index (BMI). Basal LH levels correlated inversely with BMI. Nonobese women with PCOS had a higher LH response to GnRH than obese women with PCOS. Only obese women with PCOS showed insulin resistance and fasting hyperinsulinemia. CONCLUSIONS: The data suggest that women with PCOS may be divided into two subgroups: those with obesity, insulin resistance, hyperinsulinemia, and normal/minimally elevated LH levels and those with normal BW, elevated LH levels, and normoinsulinemia. PMID- 1521641 TI - Macroprolactinomas with suprasellar extension: effect of bromocriptine withdrawal during one or more pregnancies. AB - OBJECTIVE: To investigate the effects of bromocriptine withdrawal during one or more pregnancies in patients who presented with pituitary macroprolactinomas with suprasellar extension. DESIGN: Four infertile patients presenting with a macroprolactinoma with suprasellar extension conceived during treatment with bromocriptine on 10 occasions resulting in eight full-term normal deliveries. Treatment was withheld shortly after conception in each pregnancy. RESULTS: Serum prolactin (PRL) levels fell initially from a mean of 2,776 (range 1,682 to 4,515) to 27 micrograms/L (range 1 to 71) with the development of a partially empty sella in all patients. Recovery of visual field defects occurred in the only affected individual. In case 1, PRL levels remained within the normal range, after bromocriptine withdrawal in the first pregnancy, with the development of an empty sella. Prolactin levels, however, increased substantially in cases 2 to 4. An asymptomatic suprasellar tumor extension returned in cases 2 and 3. After two or more pregnancies (cases 1, 3, and 4), there was a progressive decline in the serum PRL levels. Although still elevated in cases 3 and 4, the PRL levels were considerably below those obtained at presentation or in the first pregnancy. Tumor regression with the development of an empty sella was observed in both these patients as well in their pregnancy or postpartum period. CONCLUSIONS: Bromocriptine may be safely withdrawn during pregnancy in patients presenting with a macroprolactinoma. With multiple bromocriptine induced pregnancies, PRL levels and tumor size may progressively decrease with the eventual development of an empty sella. PMID- 1521642 TI - Relative contributions of anovulation and luteal phase defect to the reduced pregnancy rate of breastfeeding women. AB - OBJECTIVE: To evaluate the contribution of anovulation and luteal phase defects to lactational infertility. DESIGN: Prospective longitudinal follow-up. SETTING: Outpatient clinic. SUBJECTS: Forty-nine women fully nursing and amenorrheic on day 75 postpartum and 25 cycling, interval non-nursing women. INTERVENTIONS: Plasma prolactin, luteinizing hormone, estradiol (E2), and progesterone (P) levels twice a week up to the second postpartum menses. MAIN OUTCOME MEASURES: Ovulation rate and endocrine profile of the menstrual cycles. RESULTS: Ovulation rates were 37% and 97% at 6 and 12 months postpartum; 67% of ovulations occurred in amenorrhea. The luteal phase was shorter, and E2 and P levels were lower in lactating women than in non-nursing women. These parameters were closer to normal in the second cycle than the first, in spite of active nursing. The risk of ovulation and pregnancy in amenorrhea was 27.7% and 0.9% at month 6 postpartum. After the first menses, these risks were 93% and 7%, respectively. CONCLUSION: The abnormal endocrine profile of the first luteal phase offers effective protection to women who ovulate during lactational amenorrhea within the first 6 months after delivery. Later luteal phases are improved and women are at risk of pregnancy. PMID- 1521643 TI - Effects of clomiphene citrate on pituitary luteinizing hormone and follicle stimulating hormone release in women before and after treatment with ethinyl estradiol. AB - OBJECTIVE: To evaluate the effects of clomiphene citrate (CC) on pituitary luteinizing hormone (LH) and follicle-stimulating hormone (FSH) release in hypoestrogenic women and in the same women after treatment with ethinyl estradiol (EE2). DESIGN: The study was of a prospective nature and was conducted on selected patients. SETTING: Volunteer women were studied in a tertiary care public hospital. PATIENTS: The 10 patients studied were selected on the basis of hypogonadal status (menopause, premature ovarian failure, or gonadal dysgenesis and Turner phenotype) and no hormonal treatment. INTERVENTIONS: Gonadotropin releasing hormone (GnRH) was continually infused at the dose of 0.2 micrograms/min for 4 hours before and after the use of CC and/or EE2. MAIN OUTCOME MEASURE: The study was performed with the objective of determining the effect of estrogen (E) levels on the action of CC on in vivo gonadotropin release. RESULTS: In the presence of hypoestrogenic conditions, CC had no pituitary action. However, after EE2 treatment CC promoted greater FSH release and a significant inhibition of LH release from the pituitary. CONCLUSION: Clomiphene citrate needs a basal E level to be able to act on the pituitary. In normoestrogenic states and under GnRH stimulation, CC preferentially promotes FSH release while presenting a predominantly inhibitory effect on LH release. PMID- 1521644 TI - Hysteroscopic findings after missed abortion. AB - OBJECTIVE: To identify the relation of missed abortions and intrauterine pathology. DESIGN: A postabortal hysteroscopy was performed 8 to 12 weeks after a dilatation and curettage (D&C) for missed abortion. SETTING: Department of Obstetrics and Gynecology, Assaf Harofeh Medical Center, Zerifin, Israel. PATIENTS: Sixty patients after a D&C for a missed abortion. MAIN OUTCOME MEASURES: The hysteroscopic appearance of the uterine cavity. RESULTS: Intrauterine adhesions occurred in only 10 patients (16.7%) with most of them of the mild type. A previous missed abortion was recorded in 60% of these cases. Uterine anomaly was found in one quarter of the cases, mainly an incomplete uterine septum. CONCLUSION: We believe that missed abortion does not predispose for intrauterine adhesions to the extent that was previously believed. A partial uterine septum is a major factor predisposing for the occurrence of missed abortion. Hysteroscopy after a missed abortion is an easy and efficient means for both identifying such uterine anomaly and excluding intrauterine adhesions. PMID- 1521645 TI - Detection of antiendometrial antibodies in patients with endometriosis: methodological issues. AB - OBJECTIVE: To determine if methodological reasons explain previous inability of a single investigator to detect antiendometrial antibodies in patients with endometriosis by indirect immunofluorescence (IIF). DESIGN: Sera of selected patients were tested by standard IIF and recently reported methodology. Alternate diluent experiments were conducted to explain discordant results. SETTING: Sera were obtained preoperatively, and testing was completed in an institutional research laboratory. Results are compared with surgical findings. PATIENTS/PARTICIPANTS: Patients, seven with endometriosis and six without endometriosis, 40 years of age or less who are presenting for gynecological surgery. INTERVENTIONS: None. MAIN OUTCOME MEASURES: Indirect immunofluorescence was graded according to the presence or absence of cytoplasmic staining, intensity of the staining, and the lowest dilution at which staining was observed. RESULTS: The standard IIF method repeatedly demonstrated the presence of cytoplasmic staining for the presence of antiendometrial antibodies in patients with endometriosis, whereas modified methods did not produce similar positive staining results. During the alternate dilution experiments, when fluorescein isothiocyanate conjugate (FITC) was diluted in animal sera, negative results were obtained. CONCLUSIONS: The variations used in alternate methodology and failure to titrate FITC reported by other investigators are possible reasons for false-negative results reported. PMID- 1521646 TI - An office semiquantitative serum human chorionic gonadotropin determination. AB - OBJECTIVE: To compare the human chorionic gonadotropin (hCG) concentration, established by a standard serum quantitative hCG fluorescent immunoassay and a semiquantitative serum determination. DESIGN: Patients were asked to give two serum samples early in pregnancy to establish the accuracy of a semiquantitative serum hCG test in diluted and undiluted serum samples. SETTING: In a laboratory setting, two serum samples were determined; one sample was submitted for standard serum hCG radioimmunoassay, and the other was tested for hCG by the 25 IU Tandem ICON Assay (Hybritech, Liege, Belgium) in diluted and undiluted serum samples. PARTICIPANTS: Sixteen patients supposed to be pregnant. MAIN OUTCOME MEASURES: Within dilutional zones, the results of a semiquantitative hCG test were compared with a known standard quantitative serum hCG immunoassay measurements. RESULT: The semiquantitative hCG ranges of serum hCG compare fairly well with an accurate standard quantitative serum hCG immunoassay. CONCLUSION: The determination of a serum hCG range compares well with the standard quantitative serum hCG immunoassay (First International Reference Preparation) and can be completed within 15 minutes. This office semiquantitative serum hCG determination proved to be a quick and reliable test. PMID- 1521647 TI - Effects of melatonin on progesterone production by human granulosa lutein cells in culture. AB - OBJECTIVE: To test the hypothesis that melatonin modulates steroid synthesis in the human ovary. DESIGN: Granulosa lutein cells obtained from in vitro fertilization cycles were cultured in medium containing melatonin and human chorionic gonadotropin (hCG). RESULTS: Progesterone (P) secretion by granulosa lutein cells increased progressively in both basal and hCG-stimulated conditions, up to 96 hours in culture, plateaued at 144 and decreased thereafter. Melatonin (10(-7), 10(-9), 10(-11) M) had no effect on basal P or 17 beta-estradiol production. The addition of melatonin to the hCG-treated granulosa lutein cells significantly (P less than 0.05) potentiated the stimulatory effect of hCG on P production. The effect was most prominent after 144 and 196 hours of incubation. CONCLUSION: This observation suggests a role for melatonin in the intraovarian control of P production in the human ovary. PMID- 1521648 TI - Estradiol stimulates the secretion of prostacyclin and thromboxane from endometrial stromal cells in culture. AB - OBJECTIVE: To determine the production of the vasoactive prostaglandins (PGs), prostacyclin, and thromboxane (TX) in endometrial stromal cell cultures and their steroid modulation by sex steroids. DESIGN: Primary stromal cell cultures with steroid modulation in tissues from the follicular and luteal phases of normal women. SETTING: Laboratories of the Division of Reproductive Endocrinology and tissues obtained from normal patients at the Los Angeles County and University of Southern California Medical Center in Los Angeles, California. MEASURES: Stromal cell tissue culture for 14 days. Radioimmunoassay of 6-keto-PGF1 alpha, TXB2, and prolactin (PRL) as well as determination of protein content. RESULTS: Estradiol stimulated 6-keto-PGF1 alpha production more than TXB2. This effect occurred after day 6 and was as much as 10-fold greater in luteal phase tissue. The effect was eliminated by progestins that alone had no effect. This modulatory response was greater in luteal endometrial tissue than in follicular phase tissue. As expected, in these tissues progestin stimulated PRL, an effect opposite to its negative influence on the vasoactive PGs. CONCLUSION: These data provide evidence for a steroid-related influence on the balance of vasoactive PGs in the stroma of the endometrium. PMID- 1521649 TI - The impact of embryonic development and endometrial maturity on the timing of implantation. AB - OBJECTIVE: To gain insight into the peri-implantation period in the human and to answer the question whether timing of nidation is dependent on the stage of embryonic development, endometrial maturation, or a possible dialogue between the two. DESIGN: Seventy-five women underwent embryo transfer (ET) throughout 93 cycles. Thirty-three ETs resulted in viable pregnancies and deliveries. These pregnancy cycles were used for embryonic signal detection. Embryos of identical age were transferred onto hormonally and histologically defined endometria of different maturational stages (days 15 to 19). Human chorionic gonadotropin (hCG) was measured by a hypersensitive chemiluminescence assay in maternal serum every 1 to 5 days to detect the first embryonic signal. RESULTS: Individual linear regressions of hCG versus embryonic age and endometrial maturation were performed on 33 viable pregnancy cycles (r2 = 90.5% to 99.9%, P less than 0.02 to 0.002). First signal detection was restricted to an embryonic age of 7.1 +/- 0.28 (mean +/- SD) days (range 6.6 to 7.4) irrespective of endometrial maturation. The pattern of hCG detection was triphasic, described by a sigmoidal curve with the maximal slope corresponding to an hCG doubling time of 15.9 hours. Embryo transfers on cycle day 19 had a steeper slope of hCG detection than days 15 and 16 (P less than 0.05). CONCLUSIONS: First embryonic signal detection (presumed window of implantation) extends between cycle days 20 and 24. Implantation is dependent on embryonic age and is independent of endometrial maturation within this window. The timing and sigmoidal pattern of hCG detection coincides with structural changes of the implantation bed. The steeper slope of late ETs may represent a compensatory mechanism for late maternal recognition of pregnancy for corpus luteum rescue. PMID- 1521650 TI - The effect of egg yolk medium on human sperm binding in the hemizona assay. AB - OBJECTIVE: To evaluate, using the hemizona assay (HZA), whether egg yolk treatment of human sperm enhances binding to the human zona pellucida in vitro and to determine whether such a treatment is as efficient as the standard swim-up procedure for promoting sperm binding ability. DESIGN: Ejaculates were divided into aliquots and half incubated at 37 degrees C for 21 hours in standard culture medium or combined with buffered medium containing chicken egg yolk and stored at 4 degrees C for 21 hours. A second set of ejaculates were split and processed by a standard 1-hour rise alone or treated with egg yolk medium. SETTING: University teaching hospital. PARTICIPANTS: Two healthy sperm donors. MAIN OUTCOME MEASURE: The number of sperm tightly bound to the hemizona were measured and compared between the groups. RESULTS: A significant increase (P less than 0.0001) in hemizona binding (n = 46) for egg yolk treatment (90.1 +/- 9.8; range 7 to 258) as compared with standard culture medium (53.0 +/- 8.8; range 0 to 228) was observed. Similarly, a significant increase (P less than 0.0001) in binding (n = 37) for egg yolk treatment (74.9 +/- 8.2; range 7 to 219) as compared with samples obtained with a sperm rise (37.1 +/- 5.7; range 2 to 122). CONCLUSIONS: Treatment of human spermatozoa with an egg yolk medium at 4 degrees C overnight significantly increases sperm binding in the HZA. PMID- 1521651 TI - A prospective controlled evaluation of TEST-yolk buffer in the preparation of sperm for human in vitro fertilization in suspected cases of male infertility. AB - OBJECTIVE: To evaluate sperm preincubation in tes and tris (TEST)-yolk buffer as a potential enhancing agent of fertilizing capacity of sperm during human in vitro fertilization (IVF). DESIGN: Oocytes obtained during IVF were divided into two groups: one group fertilized with TEST-yolk buffer-treated sperm and the other group with standard-prepared sperm. SETTING: The University of Southern California IVF Program. PATIENTS: Thirty-nine couples with suspected male factor infertility undergoing IVF. INTERVENTIONS: Preinsemination incubation of sperm in TEST-yolk buffer for 24 hours. MAIN OUTCOME MEASURES: Fertilization rates in vitro. RESULTS: TEST-yolk buffer-treated sperm fertilized 140 of 241 oocytes (58%), whereas control sperm fertilized 108 of 251 oocytes (43%). Of four couples who had previously failed to fertilize during IVF, one fertilized with both specimens and three fertilized with TEST-yolk buffer-treated sperm only. CONCLUSIONS: TEST-yolk buffer pretreatment of sperm for 24 hours results in higher fertilization rates during IVF among suspected male factor patients. PMID- 1521652 TI - Prediction of in vitro fertilization outcome by sperm penetration assay with TEST yolk buffer preincubation. AB - OBJECTIVE: To evaluate sperm penetration assay (SPA) value as a screening tool before in vitro fertilization (IVF). DESIGN: Follow-up study comparing sperm variables and IVF outcome. SETTING: Infertile couples in an academic research environment. PATIENTS, PARTICIPANTS: Two hundred forty-one infertile couples scheduled for IVF. INTERVENTIONS: Sperm penetrating assay with cold Tes-TRIS (TEST) Yolk buffer semen preincubation and IVF. MAIN OUTCOME MEASURES: Percent of egg penetration recoded into poor and good category (0% to 20%, 21% to 100%) and compared with fertilization, embryo transfer, and pregnancy rate (PR) in IVF, as well as sperm count motility and morphology. RESULTS: Sperm penetrating assay predicted fertilization with a high negative (74%) and positive (82%) predictive rate and good specificity value (0.96). One of 31 patients in the poor SPA category (3%) fertilized less than 50% of eggs; no pregnancy occurred. In the good SPA category, 87 of 210 patients (41%) fertilized greater than or equal to 50% of eggs with 34.3% PR. Sperm penetrating assay correlated better with fertilization rate than did sperm count and motility but not morphology. CONCLUSIONS: Sperm penetrating assay is a useful screening assay before IVF together with sperm morphology. PMID- 1521653 TI - Randomized, prospective comparison of luteal leuprolide acetate and gonadotropins versus clomiphene citrate and gonadotropins in 408 first cycles of in vitro fertilization. AB - OBJECTIVE: To compare luteal phase leuprolide acetate (LA) initiated pituitary down regulation followed by human menopausal gonadotropins (hMG) versus clomiphene citrate (CC) and hMG for follicular recruitment and oocyte maturation before in vitro fertilization (IVF). DESIGN: Randomized, prospective comparison in first cycles of IVF. SETTING: University Hospital, a tertiary referral center offering assisted reproductive technologies. PARTICIPANTS: Participants were couples undergoing their first ever cycle of IVF and consenting to participation in the trial. RESULTS: Luteal phase initiated LA/hMG was associated with a lower probability of cycle cancellation, improved folliculogenesis, and a higher probability of embryo transfer (ET) compared with CC/hMG alone. Implantation rates were not different. CONCLUSION: A higher rate of ET with LA/hMG suggests that gonadotropin-releasing hormone agonist for the induction of folliculogenesis before IVF may be appropriate. PMID- 1521654 TI - Improved pregnancy rate after transfer of embryos grown in human fallopian tubal cell coculture. AB - OBJECTIVE: To evaluate the embryonic behavior in vitro and the pregnancy and implantation rates of embryos grown in a human ampullary cell coculture system. DESIGN: In a prospective study, two pronuclei embryos were cultured on human ampullary feeder layers up to the two to six-cell and blastocyst stages and replaced either as tubal, uterine, or sequential transfers. SETTING: Assisted reproductive technology program in a university-based hospital. PATIENTS: Fifty women with a mean age of 35.6 years who went through a single coculture cycle. Thirty of the patients were admitted for in vitro fertilization (IVF) and 20 for tubal embryo transfer (TET). RESULTS: The overall clinical pregnancy rate (PR) for all 50 patients was 44% per cycle (IVF, 37%; TET, 55%) and the implantation rate was 31.8% (IVF, 31.0%; TET, 32.6%). Sixty-eight percent of pregnant patients were over 35 years, and 68% had two previously failed assisted reproduction cycles. Five of 9 patients who received sequential transfers became pregnant. Three of the 22 pregnancies aborted (2 after sequential transfer), and there was one ectopic. Overall, 88% of two to six-cell stage embryos were of good quality. CONCLUSIONS: The human ampullary coculture system produces better quality embryos, increased numbers of blastocysts with improved PRs and implantation rates. The beneficial effects of the feeder layer may be through the release of embryotrophic factors and detoxification of the medium by the cells. Coculture is a new concept in assisted reproduction and has tremendous potential in boosting conception rates by mimicking the in vivo environment. PMID- 1521655 TI - The role of oocyte maturity in the treatment of infertility because of teratozoospermia and normozoospermia with gamete intrafallopian transfer. AB - OBJECTIVE: To determine the effect of oocyte maturity on pregnancy rate (PR) in patients undergoing gamete intrafallopian transfer (GIFT) procedures for infertility and in whom male partners had either normozoospermia or teratozoospermia. DESIGN: A prospective study using a combination of clomiphene citrate and human menopausal gonadotropin for ovulation induction was carried out. Five hundred thirty-seven GIFT treatment cycles were analyzed, and 423 cycles yielded four or more oocytes. Patients were divided into two groups according to the sperm morphology: those with less than 14% normal forms and those with greater than 14% normal morphology (as judged by strict criteria). These two groups were divided into a further five subcategories depending on the number of metaphase II oocytes transferred. RESULTS: In the group less than 14% normal forms (category I; 4 metaphase I oocytes replaced), three pregnancies resulted from 33 cycles (9.09%), and in category V (4 metaphase II oocytes transferred) the PR was 15% (14/95) per cycle. In the group with greater than 14% normal forms, in category I, the PR was 16% (3/19) per cycle, and in category V, the PR was 33% (20/61) per cycle. The effect of morphology (less than 14% normal forms versus greater than 14% normal forms) on pregnancy outcome is significant (P = 0.0161). The overall effect of increasing the number of metaphase II oocytes on the pregnancy outcome was not significant (P = 0.1098). However, in the group with greater than 14% normal forms, there was a significant improvement in PR (P = 0.04) in category V. CONCLUSION: During this prospective study, it was shown that sperm morphology plays a significant role in the pregnancy outcome in a GIFT program. PMID- 1521656 TI - Failure of intrauterine insemination in male immunological infertility in cases in which all spermatozoa are antibody-coated. AB - OBJECTIVE: To determine if the overcoming of the cervical mucus barrier removes the interference of sperm-bound antibodies with fertility. DESIGN: Prospective case series. SETTINGS: University-based intrauterine insemination (IUI) homologous program. PATIENTS: Nineteen patients with all spermatozoa in the ejaculate coated by antisperm antibodies. As control group, 86 consecutive patients without antisperm antibodies, treated for oligoasthenozoospermia or mucus hostility. INTERVENTIONS: Intrauterine inseminations (at least 3 attempts per couple). MAIN OUTCOME MEASURES: The outcome of IUIs, demographic, and seminal parameters were compared between the two groups. RESULTS: No pregnancy occurred in the couples with male immunological infertility, treated by 110 IUIs. Twenty three pregnancies occurred in 22 (25.6%) of the control group couples who were treated by 411 IUIs. In the group of patients without antisperm antibodies, we demonstrated that the pregnancy rate (PR)/couple in oligoasthenozoospermia without teratozoospermia was similar to that achieved in normozoospermia (35% versus 38.9%), whereas it was significantly affected by teratozoospermia (3.6%). Only three patients with antisperm antibodies had teratozoospermia. Comparing the PR per couple and per cycle between the two groups of patients (with and without antisperm antibodies), excluding the patients with teratozoospermia, significant differences resulted (P less than 0.005 and P less than 0.005, respectively). The motile sperm count was not significantly different between the two groups, which also resulted to be homogeneous for demographic data. Moreover, the motile sperm count was not different between the patients with and without antisperm antibodies, who had successful IUI. CONCLUSIONS: The analysis of this trial suggests that the failure of IUI in the treatment of male immunological infertility is imputable to antisperm antibodies when they involve all spermatozoa, regardless of semen quality. PMID- 1521657 TI - Identification of human sperm antigens reacting with antisperm antibodies from sera and genital tract secretions. AB - OBJECTIVE: To identify sperm antigens reacting with antisperm antibodies relevant in human infertility. DESIGN: The reactions of separated sperm antigens with antibodies present in sera and genital tract secretions from infertile and fertile females and males were examined by immunoblotting techniques. SETTING: The patients were followed in an outpatient setting of a hospital clinic. PATIENTS: One hundred consecutive infertile males and females, referred for determinations of antisperm antibodies, comprised the study group. Fifty hospital and faculty employees with proven fertility served as a control group. RESULTS: A high proportion of sera from fertile and infertile humans contained antibodies reacting with at least one sperm antigen. However, two discrete bands of antigenic proteins with molecular weights of 44 and 72 kd reacted significantly more frequently with serum antibodies from infertile females than from fertile females. No apparent correlation could be demonstrated between any particular antigen and serum antibodies from infertile males. Nevertheless, antigenic proteins of 62 kd were identified as the major sperm antigens reacting with antibodies present in seminal plasmas from infertile males. CONCLUSIONS: The major sperm antigens reacting with systemic antibodies differ from the antigens recognized by local antisperm antibodies. Sperm antigens exhibiting relative molecular weights of 62 kd are major antigens reactive with local antisperm antibodies from infertile humans. PMID- 1521658 TI - High progesterone concentrations induce acrosome reaction with a low cytotoxic effect. AB - OBJECTIVE: To determine the optimal conditions to obtain live acrosome-reacted spermatozoa for micromanipulation. DESIGN: Experiments were performed to determine time and dose-dependent effects of calcium ionophore A23187 or steroids on acrosome reaction of fertile donor sperm. The percentages of total reacted and live reacted spermatozoa were assessed with the peanut agglutinin lectin procedure. RESULTS: Incubation with 1 mmol/L progesterone (P) induced 48% +/- 17% acrosome reaction after 6 hours. Motility and viability remained high (49% +/- 3% and 70% +/- 2%, respectively) and thus the percentage of live reacted spermatozoa was 27% +/- 5%. Incubation with A23187 (5 mumol/L for 30 minutes) gave similar results for the percentage of live reacted spermatozoa (26% +/- 4%) but with a lower motility and viability (25% +/- 7% and 53% +/- 2%, respectively; P less than 0.05). CONCLUSIONS: These results show that high concentration of P is an effective way to induce acrosome reaction in preparation for micromanipulation. PMID- 1521659 TI - Unilateral obstruction of the vas deferens caused by childhood inguinal herniorrhaphy in male infertility patients. AB - OBJECTIVE: To study the incidence, diagnosis, and treatment of unilateral obstruction of the vas deferens caused by inguinal herniorrhaphy (IH) during childhood. DESIGN: Retrospective. SETTING: Kyoto University Hospital. PATIENTS: Unilateral obstruction of the vas deferens after IH was diagnosed and treated in 10 of 724 subfertile patients. INTERVENTIONS: Reanastomosis of the vas deferens using a microsurgical two-layer technique. MAIN OUTCOME MEASURES: Follow-up seminal analysis of the patients and the occurrence of pregnancy in their wives. RESULTS: The incidence of unilateral vas deferens obstruction caused by IH was 26.7% for subfertile patients with a history of IH during childhood. Unilateral vas deferens obstruction was detected through palpation of the scrotal vas deferens in 7 of the 10 patients. After vasovasostomy, the semen quality improved in 5 patients, and pregnancy was achieved by 2 patients. CONCLUSIONS: The incidence of vas deferens obstruction was unexpectedly high in subfertile patients with a history of IH during childhood. Careful palpation of the scrotal content was a useful and noninvasive method to diagnose unilateral vas deferens obstruction, and microsurgical vasovasostomy was treatment of choice. PMID- 1521660 TI - Body weight, body mass index, and age: predictors of menotropin dose and cycle outcome in polycystic ovarian syndrome? AB - Whereas the dose of hMG is significantly correlated with both BMI and BW, commencing the more obese patient on higher hMG doses is not justified in view of the cancellation of cycles from over-responsiveness in the more obese patients started on higher hMG dosage regimens. If the more obese patient is slow to respond, however, a greater degree of clinical freedom may be exercised to increase the dose. The ultimate outcome of the cycle is not related to BMI, BW, or the dose of hMG used. PMID- 1521661 TI - Evaluation of Astroglide, a new vaginal lubricant: effects of length of exposure and concentration on sperm motility. AB - Traditional vaginal lubricants have been shown to adversely affect sperm motility. Astroglide, a new vaginal lubricant, and K-Y Jelly were tested at varying concentrations to assess their suitability for infertility patients requiring a lubricant. The vaginal lubricants tested impaired sperm motility in a concentration-dependent but not time-dependent manner. We conclude that all traditional vaginal lubricants should be avoided in patients desiring conception. Future studies should attempt to mimic in vivo conditions and focus on concentration-dependent effects. PMID- 1521662 TI - Flow cytometric quantitation of the expression of membrane cofactor protein as a marker for the human sperm acrosome reaction. AB - A mAb (TRA-2-10, IgG1) to an embryonal carcinoma cell line (2102ep) that recognizes an antigen termed membrane cofactor protein (CD 46, TLX antigen) binds to human sperm after chemical induction of acrosomal loss by Ca2+ ionophore. An indirect immunofluorescence assay was developed in which sperm membrane cofactor protein was detected by flow cytometry on acrosome-reacted living human sperm. The expression of the membrane cofactor protein antigen on acrosome-reacted sperm may represent a marker that can be used in a rapid, quantitative, and reproducible flow cytometric assay for the evaluation of human sperm acrosomal loss. PMID- 1521663 TI - Comparison of results obtained with human serum and a protein solution as a supplement for in vitro fertilization culture medium. AB - A prospective controlled study was performed to compare the PRs obtained after use of a uniform IVF culture medium containing a pasteurized serum protein solution or patient serum. The ongoing PRs per ET in the serum and the protein solution group were 32% and 28%, respectively (not significant). Culture of supernumerary embryos showed blastocyst formation and even hatching with both supplements. The PR will not drop when this protein solution is used as a protein supplement in IVF culture medium instead of patient serum. PMID- 1521664 TI - An improved needleholder for endoscopic knot tying. AB - A needle holder fitted with a distal and rotating hook is described. During endoscopic suturing, this hook grasps the thread and forms automatically a loop, through which the distal end of the thread is pulled to secure the knot. Endoscopic intracorporeal knot tying thus becomes easier and faster, especially in difficult situations. PMID- 1521665 TI - Dose and frequency for pulsatile GnRH. PMID- 1521666 TI - Microinjection of human oocytes. PMID- 1521667 TI - Editorial comment. The maternal legacy: "maternal effect proteins". PMID- 1521668 TI - Anti-proliferative effect on human pancreatic cancer cells of natural human tumour necrosis factor-beta combined with natural human interferon-alpha or interferon-gamma. AB - The anti-proliferative effects of natural cytokines, human tumour necrosis factor beta, natural human interferon-alpha and natural human interferon-gamma, on three human pancreatic cancer cell lines (PANC-1, MIA PaCa-2 and BxPC-3) were investigated in vitro. The anti-proliferative effect was determined using the dye uptake method and analysed for synergism by the median effect principle. Tumour necrosis factor-beta, as a single agent, had little anti-proliferative effect on any of the three cell lines, whereas interferon-alpha and interferon-gamma exhibited a strong anti-proliferative effect against two cell lines (MIA PaCa-2 and BxPC-3) and one cell line (BxPC-3), respectively. When tumour necrosis factor beta and interferon-alpha were administered together (ratio 1:1), a synergistic effect was observed against PANC-1 cells. The combination of tumour necrosis factor-beta and interferon-gamma (ratio 10:1) was synergistic against both PANC-1 and MIA PaCa-2 cells. A synergistic anti-proliferative effect of tumour necrosis factor-beta and interferons was, therefore, observed even for cell lines that showed little biological response to each cytokine alone. The data suggest that some future improvement in the treatment of pancreatic cancer may be obtained by using combination cytokine therapy. PMID- 1521669 TI - Effects of mexiletine on the haemodynamic responses to tracheal intubation. AB - The efficacy of intravenous mexiletine in attenuating the cardiovascular responses to laryngoscopy and tracheal intubation was studied in 30 normotensive patients undergoing elective surgery. The patients were randomly allocated to one of three treatment groups: saline (n = 10); 2 mg/kg mexiletine (n = 10); and 3 mg/kg mexiletine (n = 10). The placebo/mexiletine was administered immediately before induction of anaesthesia using 5 mg/kg thiopentone and tracheal intubation was facilitated with 0.2 mg/kg vecuronium; laryngoscopy lasting 30 s was attempted 2 min after induction of anaesthesia. All groups showed a significant (P less than 0.05) increase in mean arterial pressure and heart rate associated with tracheal intubation. The increase in mean arterial pressure was significantly (P less than 0.05) smaller in patients receiving 3 mg/kg mexiletine compared with those receiving either saline or 2 mg/kg mexiletine. There was no significant attenuation in heart rate in either of the mexiletine treatment groups compared with the saline group. It is concluded that 3 mg/kg mexiletine given intravenously provides a simple and effective method for attenuating the pressor response to laryngoscopy and tracheal intubation. PMID- 1521670 TI - Multicentre clinical placebo-controlled study with buflomedil in the treatment of mild dementia of vascular origin. AB - A study was carried out in 73 male or female patients suffering from mild vascular dementia. The experimental protocol involved an initial run-in period (14 days) and subsequent double-blind, randomized treatment with 300 mg buflomedil or placebo given orally twice daily for 90 days. At the end of this treatment period, all patients received buflomedil for a further 90 days and, thereafter, patients received buflomedil or no further treatment for another 90 days. The efficacy of buflomedil was monitored using rating scales and neuropsychological tests. The findings of the study indicate that buflomedil improved the symptoms of vascular dementia; the most improvement was recorded in patients who had received buflomedil for the longest period. Inadequacy, cooperation, psycho-affective disorders, self-care and somatic complaints were positively influenced by buflomedil. The efficacy of buflomedil may be due to its effects on platelet aggregation and improvement in blood flow distribution to the ischaemic brain and oxygenation of brain tissue. PMID- 1521671 TI - A double-blind, comparative study of zolpidem and placebo in the treatment of insomnia in elderly psychiatric in-patients. AB - The efficacy and tolerability of the imidazopyridine hypnotic, zolpidem, were investigated in 119 elderly psychiatric in-patients complaining of insomnia in a double-blind, parallel-group, placebo-controlled trial. After a 7-day placebo washout period, patients were randomized to receive 10 or 20 mg/day zolpidem, or placebo for 21 days; thereafter, all patients received placebo for 7 days. Sleep was assessed by patient observation on days 0, 1, 7, 14, 21, 22 and 28. Compared with placebo, 20 mg/day zolpidem significantly improved total duration of sleep between day 0 and day 21, and this was maintained at day 28. After 10 or 20 mg/day zolpidem, there was also a trend towards improvement in all other sleep parameters, which remained above baseline at day 28. Zolpidem was well tolerated with no withdrawal symptoms during the second 7-day placebo treatment period. Daytime drowsiness was reported in three patients receiving 20 mg/day zolpidem and in one receiving 10 mg/day zolpidem, but there was no significant increase in daytime drowsiness between days 0 and 21. Ataxia occurred in two, one and one patient, respectively, treated with 20 mg/day zolpidem, 10 mg/day zolpidem and placebo. The incidences of other adverse events or effects on clinical and laboratory parameters were minimal and similar in all three treatment groups. It is concluded that, in elderly psychiatric patients, 10 mg/day zolpidem can be used to treat insomnia and can be safely added to concomitant psychotropic treatment without inducing daytime drowsiness. PMID- 1521672 TI - The safety and efficacy of zolpidem in insomniac patients: a long-term open study in general practice. AB - The safety and efficacy of 10 or 20 mg/day zolpidem, a new hypnotic belonging to the imidazopyridine class, were studied over a 180-day period in 96 patients with sleep disorders. The treatment was continued for a further 180 days by 49 of these patients. Follow-up information from 21 patients who discontinued treatment after 180 days showed no rebound insomnia or withdrawal signs. Efficacy of treatment with respect to reduction of sleep onset latency and number of nocturnal wakenings, and improvement in duration of sleep, quality of sleep and morning wakenings was found in nearly 90% of patients and was maintained in those patients who continued treatment for 360 days. This efficacy was achieved with a stable percentage of patients receiving 10 mg/day and 20 mg/day zolpidem from day 30 to the final visit. Zolpidem, therefore, has been shown to be an effective and safe hypnotic, and to be devoid of rebound and withdrawal effects. PMID- 1521673 TI - Clinical improvement in ankylosing spondylitis with rifamycin SV infiltrations of peripheral joints. AB - In an open study, a new treatment modality was evaluated in 22 patients with active ankylosing spondylitis and compared with oral treatment. Patients were given a 10-week course of rifamycin SV infiltrations to all large peripheral joints, whether or not affected, and were followed for up to 12 months after the end of treatment. Clinical improvements observed at the end of the 10-week treatment cycle persisted for 12 months: morning stiffness (P less than 0.02); subjective pain (P less than 0.0001); Schober's test (P less than 0.006); hand ground distance (P less than 0.001); erythrocyte sedimentation rate (P less than 0.001); and C-reactive protein (P less than 0.04). The number of painful joints became significantly lower at 6 (P less than 0.01) and 12 months (P less than 0.02) of the follow-up period. Oral administration of rifampin at three times the intra-articular dosage was devoid of any therapeutic activity. It is not known how treatment of peripheral joints influenced the inflammatory process at the level of the axial skeleton. These results must be considered preliminary due to the small number of patients and the short follow-up period, and because it was an open study. PMID- 1521674 TI - Primary fibromyalgia syndrome and 5-hydroxy-L-tryptophan: a 90-day open study. AB - The efficacy and tolerability of 5-hydroxy-L-tryptophan (5-HTP) were studied in an open 90-day study in 50 patients affected by primary fibromyalgia syndrome. When all the clinical variables studied throughout the trial (number of tender points, anxiety, pain intensity, quality of sleep, fatigue) were compared with baseline results, they all showed a significant improvement (P less than 0.001). The overall evaluation of the patient condition assessed by the patient and the investigator indicated a 'good' or 'fair' clinical improvement in nearly 50% of the patients during the treatment period. A total of 15 (30%) patients reported side-effects but only one patient was withdrawn from the treatment for this reason. No abnormality in the laboratory evaluation was observed. It is concluded that 5-HTP is effective in improving the symptoms of primary fibromyalgia syndrome and that it maintains its efficacy throughout the 90-day period of treatment. PMID- 1521675 TI - Does a dose of 40 micrograms/day prostaglandin E1 reduce creatinine clearance in a patient with diabetic nephropathy of the nephrotic type? AB - The case history of a woman, who at the age of 25 years on the birth of her second child was found to be diabetic, is reported. Over the subsequent 30 years the patient had been treated with insulin, the dose administered being monitored at regular intervals. At the age of 52 years, the patient was diagnosed as suffering from hypertension and diabetic nephropathy of the nephrotic type. The patient's condition gradually deteriorated and at 55 years of age 40 micrograms/day prostaglandin E1 was given intravenously for 84 days. Treatment resulted in a decline in urinary protein without a reduction in creatinine clearance. Renograms confirmed an improvement in the vascular and secretory phases of both kidneys. PMID- 1521676 TI - Special natural cartilage polysaccharides for the treatment of sun-damaged skin in females. AB - In the present double-blind investigation, the effects of a new formulation of natural cartilage polysaccharides on sundamaged skin were studied in women aged 40-60 years. A group of 15 women were treated orally with 500 mg/day active substance (Vivida) for 90 days and a second group of 15 women received 500 mg/day placebo for 90 days. Clinical examinations after 45 and 90 days' treatment showed significant improvements in skin condition in the actively treated group but not in the placebo group (P less than 0.001). In the Vivida-treated patients, the epidermal thickness increased after 90 days from 0.11 mm to 0.29 mm, dermal thickness from 0.74 mm to 1.39 mm, skin elasticity index from 44% to 73% and the erythemal index decreased from 0.301 to 0.205. No changes were observed in the placebo group and no adverse effects were reported by either treatment group. PMID- 1521677 TI - Chemical characterization of the dentin/adhesive interface by Fourier transform infrared photoacoustic spectroscopy. AB - Irreversible bonding of composite materials to tooth structure depends on chemical as well as mechanical adhesion. The proposed bonding mechanism for several commercial dental adhesives is chemical adhesion to the dentin surface. The purpose of this in vitro investigation was to characterize the chemical nature of the surface interaction between dentin and two commercial adhesives by use of Fourier transform infrared photoacoustic spectroscopy (FTIR/PAS). The occlusal thirds of the crowns of freshly extracted, non-carious, unerupted human molars were sectioned perpendicular to the long axis. Dentin disks, 6 mm x 2 mm, were prepared from these sectioned teeth. The exposed dentin surface was treated with either Scotchbond 2, a BIS-GMA resin, or Dentin-Adhesit, a polyurethane resin. All spectra were recorded from 4000 to 400 cm-1 by use of an Analect RFX 65 FTIR spectrometer equipped with an MTEC Photoacoustics Model 200 photoacoustic cell. An initial spectrum of the dentin surface was collected. This surface was primed according to manufacturer's instructions and spectra recorded of the primed surface plus one to three layers of adhesive. By comparison of these spectra, it was possible for us to record changes in the phosphate and amide I and II bands due to surface interactions between the adhesive and the dentin. Although early results do not indicate covalent bonding between the dentin and these adhesives, this technique presents several advantages for spectroscopic evaluation of the dentin/adhesive interface. PMID- 1521678 TI - Inhibition of microbial adherence and growth by various glass ionomers in vitro. AB - This study measured the in vitro inhibition of growth and adherence of five oral bacteria by glass-ionomer materials. Disks were prepared from two cavity liners and four restorative class materials, by use of Teflon plates with circular wells, five mm wide and two mm deep. The bacterial species tested included: A. viscosus, S. mitis, S. mutans, L. casei, and S. sanguis. Growth inhibition studies were performed by the spreading of 0.1 mL of standardized inocula over agar plates produced with selective media, followed by the direct application of glass-ionomer disks onto the agar. On other plates, disks were placed onto uninoculated agars for 48 h, followed by bacterial inoculation. All agar plates were incubated under optimal growth conditions for each bacterial species. The four restorative materials were also placed aseptically into sterilized bovine incisors and placed into sucrose containing broth media, inoculated with S. mutans for three days. Adhering materials were disclosed and scored. An ion exchange electrode was used to measure fluoride release over a seven-day period for all six glass ionomers. The two cavity liners and two of the restorative materials produced the largest growth inhibition zones by direct contact. No growth inhibition occurred when the specimens were allowed to come into contact with the agars prior to inoculation. All four restorative materials reduced bacterial accumulations on enamel surfaces by over 80%. Elevations in short-term fluoride release levels were positively correlated with growth inhibition. PMID- 1521679 TI - The effect of corrosive environment on the porcelain-to-metal bond--a fracture mechanics investigation. AB - Microcracks, flaws, and voids inside a metal-porcelain restoration may cause the restoration to fracture in service. Such cracks result in the concentration of stresses. The dynamic nature of the stresses due to mastication promotes crack growth. In addition, corrosive components of the oral environment enhance the growth rate. In the present investigation, fracture mechanics has been used to analyze the in vitro resistance to fracture of the porcelain-fused-to-metal restoration. The risk of a clinical failure of porcelain-fused-to-metal decreases with enlarged crack resistance (increasing work of fracture). The work of fracture represents an average of the energy for initiation and propagation of a crack through the interface separating porcelain and metal. This work also indicates a material's ability to stop a crack once it is moving. This study utilized the three-point bending test for the crack resistance measurement, and investigated one palladium and five base metal alloys. Corrosive components of the oral environment and the details of firing were of crucial importance for long-term bond stability. PMID- 1521680 TI - Effects of dentin surface treatments on the shear bond strength of Vitrabond. AB - The influences of nine dentin surface treatments were evaluated on the shear bond strength of a new light-cured glass-ionomer cement (GIC) and on the SEM morphology of the treated dentin surfaces. The following treatments were performed: saline solution (control), NaOCl, acidic glycine, EDTA, malic acid, malic acid plus glycine, polyacrylic acid, tannic acid, and neutral+acidic oxalate solutions. Buccal dentin surfaces were polished with #320-grit abrasive paper, treated with one of the chemicals, washed, and air-dried. Cylindrical GIC samples were then applied to the dentin surface, stored in 100% humidity, and tested after 24 h. SEM observations demonstrated no effect of saline or NaOCl treatment on the smear layer but its complete removal with exposure of collagen fibrils after malic or malic acid plus glycine treatment. Partial removal of the smear layer occurred following glycine treatment and with tannic or polyacrylic acids. Complete removal of the smear layer was seen after EDTA or pyruvic acid treatment. Oxalate treatment produced a layer of crystals, which completely covered the dentin surface. Shear bond strength of GIC was significantly increased only by treatment with the oxalate solutions. PMID- 1521681 TI - Microleakage comparison of dentin bonding systems with glass ionomer. AB - Glass-ionomer cements have been suggested as substitutes for dentin-bonded composites. This investigation was designed to compare microleakage of glass ionomer restorations with that of dentin-bonded composite restorations. Eighty extracted human molars were used in this study. Class V cavities were prepared on the mesial and distal surfaces of each tooth. The distal cavities were restored with Ketac-Fil Glass Ionomer (ESPE). The mesial cavities were divided into four groups and treated with four different dentin bonding systems: Gluma (Columbus Dental), Tenure (two-part powder system; second version, Den-Mat), Scotchbond 2 (3M), and an experimental ferric oxalate system. The commercial materials were placed according to the manufacturers' instructions. The teeth were then thermocycled 3800 cycles between 5 degrees C and 55 degrees C, subjected to silver nitrate staining, and sectioned for microleakage evaluation by three evaluators on a scale of 0 to 4. The ferric oxalate system exhibited significantly less microleakage (median score = 1; Wilcoxon paired testing, p = 0.01) than the glass ionomer (median score = 3). The other dentin bonding systems were similar in microleakage to the glass ionomer (median score = 3). PMID- 1521682 TI - Relationship between bond strength and microleakage measured in the same Class I restorations. AB - Microleakage measurements were made by use of a pressurized fluid method in Class I restorations prepared in extracted human teeth just prior to measuring the tensile bond strengths of the same restorations. The restorative materials included dentin bonding systems that are applied to smear layers as well as those which remove the smear layer. A light-cured glass-ionomer cement was also included. The results demonstrated that there was an inverse relationship between dentin bond strength and microleakage in some materials and that the bond strengths made to three-dimensional Class I cavities were much lower than those made to flat dentin surfaces. Measurement of microleakage by fluid filtration had no apparent effect on bond strength. PMID- 1521683 TI - International distribution of dental materials publications and patents. AB - International patterns of research and development in the field of restorative dental materials were examined with data on publications (1981-85) and patents (1979-88). It was found that United States-based authors produced approximately one-half of all dental materials journal articles published worldwide, while US inventors had nearly the same share of the US dental materials patents. During the periods studied, the share of US patents in dental materials awarded to US inventors declined, while the share of US patents awarded to Japanese inventors rose. The role of the United States in research (as measured by journal articles) remained stable. Nations differed in the degree to which their researchers specialized in particular research areas. US-based authors and inventors were relatively over-represented in prosthetic materials and under-represented in dental cements, an area in which the British and the Japanese concentrated more of their activity. There was some, but not complete, agreement in the patterns of national specialization as indexed by patent and publication data. When dental materials data were compared with data for broader fields of science and technology, important differences were found. For publications, US-based authors displayed greater dominance in dental materials than in the fields of dentistry, chemistry, and materials science. US-based inventors' share of US dental materials patents was smaller than their share of all US patents. These analyses demonstrated that it was possible to use indicators derived from publication and patent data files to conduct insightful studies of a discrete specialty of science and technology. PMID- 1521684 TI - Accuracy testing of three-dimensional digitizing systems. AB - An accuracy test designed as a standard for digital occlusal wear measurement devices was applied to such a device designed by the authors. The test was used for quantitative determination of measurement error for a given angle of tangential contact with the inclined planes of the surface being measured. Using known dimensions of the digitizer contact tip and of a precision steel sphere, we determined trigonometrically the error in the Z-axis measurement due to the slope of any point on the surface of the sphere. These values were used for a point-by point correction of data obtained from actual digitization of the sphere. The corrected values would equal zero if no mechanical source of error existed. These values, then, quantitatively indicated the accuracy (in microns) of the device as a function of the slope of the measurement point. The results indicated a linear relationship between surface slope angle and measurement error for the device tested. PMID- 1521685 TI - Cytotoxicity evaluation of a new radiopaque resin additive--triphenyl bismuth. AB - Triphenyl bismuth (Ph3Bi) is a promising new additive for making biomedical resins visible on x-ray images. We evaluated the cytotoxicity of Ph3Bi, both alone and as a component of a denture resin, as an initial step in determining its biocompatibility. These experimental materials were compared with several types of dental materials that are in current clinical use (PMMA denture acrylic resin, two photo-cured sealants, and two glass-ionomer cements). Human embryonic lung fibroblast tissue cultures (WI-38 cells) were exposed to 24-hour aqueous extracts of the materials. Changes in cell growth, cell viability, and the visual appearance of cells were used for the assessment of toxic response. Only a slight degree of cytotoxicity was observed for Ph3Bi, both alone and in combination with self-cured PMMA. All clinical materials showed a higher level of cytotoxicity than did Ph3Bi. The sealants and cements exhibited the most cytotoxicity and PMMA acrylic the least. The cytotoxicity of PMMA was elevated slightly by inclusion of Ph3Bi, probably due to decreased monomer conversion. When stored in water, the already low levels of cytotoxicity of both PMMA and PMMA with added Ph3Bi were reduced even further. From these results, we can predict a high level of safety for Ph3Bi as a radiopaque additive for biomedical resins. Any toxicity associated with Ph3Bi-containing resins can be reduced or avoided by prior extraction. Alternatively, curing conditions can be selected that would drive the polymerization reaction to a higher level of conversion. PMID- 1521686 TI - Direct and indirect evaluation of posterior composite restorations at three years. AB - The purpose of this study was to compare the use of direct (USPHS) and indirect (M-L) systems of evaluating the occlusal wear of posterior composite restorations. Additionally, this study has utilized the USPHS method to compare the in vivo performance of posterior resin composite restorations made from four different visible-light-cured materials. Of the 202 restorations placed for this randomized clinical trial, only those restorations that were scored by both direct and indirect evaluation systems were included in these comparisons. Restorations were evaluated by two calibrated examiners from baseline to 36 months. While there were some differences noted among the four materials, the majority (99%) of the restorations evaluated in this study received "alpha" or "bravo" scores for all USPHS parameters, indicating acceptable in vivo performance. The results of this study also indicate that there was a consistent relationship between the direct (USPHS) and indirect (M-L scale) scoring systems. For those restorations that changed anatomic form scores, the mean wear at the alfa/bravo transition was 100 +/- 80 microns. By the 24-month recall examination, the use of the USPHS evaluation system category of anatomic form enabled examiners to differentiate restorations and materials that had experienced little occlusal wear from those that had experienced greater amounts of wear. PMID- 1521687 TI - Precision of and new methods for testing in vitro alloy cytotoxicity. AB - Previous studies have utilized in vitro alloy cytotoxicity tests to evaluate dental casting alloys. The purposes of this study were to: (1) evaluate the precision of the optical density and visual tests previously used, (2) evaluate a new test measuring absorbance of solubilized formazan dyes, and (3) test the correlation between these tests for cytotoxicity. Balb/c 3T3 cells were plated in 24-well culture trays at 25,000 cells/cm2 around ten types of dental casting alloys (six samples/alloy) and incubated for 72 h. Cells were histochemically stained with MTT (3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl tetrazolium bromide)/succinate for 2 h, then fixed, washed, and dried. Toxicity was measured by optical densitometer (OD) scanning, visual assessment, and 560-nm absorbance of DMSO-solubilized dyes. Measurements of rings of inhibition were not used, because they did not provide precise data, and correlated poorly with the other methods. The results were analyzed by ANOVA, Tukey intervals, and coefficients of variation (CV's). MTT required shorter incubation times for adequate staining, allowed for solubilization of the monolayers, and was less expensive than NBT (2,2'-di-p-nitro-phenyl-5,5'-diphenyl-3,3'-dimethoxy-[3,3'-dimethoxy-4,4 ' biphenylene] ditetrazolium chloride). Results showed that all three methods ranked alloy toxicities similarly (p = 0.05). The solubilization method was most discriminating due to lower CV's. Correlation between densitometer and solubilization methods was excellent (R2 = 0.96). Between-experiment CV's were generally less than 20%, and often less than 10%. Between-sample CV's were generally less than 20%.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1521688 TI - Cure profiles of visible-light-cured Class II composite restorations in vivo and in vitro. AB - The degrees of conversion of posterior composite material in Class II restorations performed in vivo and in vitro were studied by means of the Raman spectroscopy method. Class II restorations in 13 contralateral pairs of premolars were analyzed. The average difference of the ratio I 1610 cm-1/I 1640 cm-1 between the in vivo- and in vitro-performed restorations was 0.42. This indicates a higher grade of conversion in the in vivo situation. PMID- 1521689 TI - Effect of loading conditions on bi-axial flexure strength of dental cements. AB - A ball-on-three-ball bi-axial flexure test was used to evaluate the flexure strengths of five kinds of dental cements (zinc phosphate, polycarboxylate, glass ionomer, silicate, and zinc oxide-eugenol cements). The bi-axial flexure strengths of zinc phosphate cement discs of variable dimensions were also measured to determine the size effects of test specimens. Finite element stress analyses were performed on disc specimens which were subjected to both a concentrated load and a uniformly distributed load. The observed values were compared with the theoretical value calculated by the finite element method. A ball-on-three-ball bi-axial flexure test could not be used for thicker specimens, since the fracture origin of these specimens is more likely to occur on the loaded side. PMID- 1521690 TI - Dimensional stability of silicone-based impression materials. AB - This study attempts to demonstrate that the polymerization reaction is not the only factor that affects the shrinkage of silicone-based impression materials because evaporation of the constituents also contributes to the shrinkage. These factors can be evaluated by the study of time-dependent dimensional changes. This is shown both by chemical kinetics and by experimental testing of condensation and addition polymerizing impression materials with different viscosities. Comparison of the different materials shows that the two contributions, polymerization shrinkage, and evaporation shrinkage, can be assessed separately by analysis of the time-dependent shrinkage diagrams. The instability due to the polymerization reaction is complete after a few hours, but the contribution of the constituent evaporation, if present, can have a significant long-term role. PMID- 1521691 TI - The colors of silver with silver nitrate staining in dental materials. AB - Silver nitrate has been used as a stain to study the permeability, degradation, and marginal integrity of dental composite restorations. The reagent results in various colors in the composite or marginal interface. So that the cause of these colors could be investigated, this study compared the appearances of the stained layers by light and electron microscopy. The results indicated that the colors could be explained by the distribution of silver particles ranging from minute colloidal particles (20 nm) in the composite or dentin, to clusters of large particles (0.1-1 micron) in marginal interfaces. The colors can be explained by the absorption and scattering of light by these particles. At elevated temperatures, fused concretions of silver formed in the composite subsurface, resulting in direct reflection of incident light. The colors which appear with silver nitrate staining may indicate the size and distribution of microporosity in the material. PMID- 1521692 TI - Effect of HEMA on bonding to dentin. AB - The present study investigated the effectiveness of treating dentin with 2 hydroxyethyl methacrylate (HEMA) prior to application of an adhesive resin. The adhesive resin was 5% 4-methacryloxyethyl trimellitate anhydride (4-META) in methyl methacrylate (MMA) combined with poly-MMA powder. Polymerization of this resin was initiated by tri-n-butyl borane (TBB). Bovine dentin samples were ground with 600-grit Carbimet paper discs, and demineralized with either an aqueous solution of 10% citric acid/3% ferric chloride (10-3) or an aqueous solution of 10% citric acid (10-0). Improved bond strengths were achieved with HEMA treatment of bovine dentin samples, and improvement of bond strengths was dependent upon the time period of HEMA application. Scanning electron microscope (SEM) examination revealed the formation of a transitional zone of resin reinforced dentin, termed the "hybrid" layer, in those specimens receiving 10-3 pre-treatment. The adhesive resin impregnated the exposed collagen bundles with which it entangled to create the "hybrid", essential in the attainment of high tensile bond strengths. Specimens pre-treated with 10-0 did not readily form "hybrid" layers. However, if HEMA application followed the 10-0 pre-treatment, "hybrids" were demonstrated on SEM, and bond strength increased to 13 MPa. The ferric ions in the 10-3 effectively improved the diffusivity of dentinal substrates, as did HEMA. This study indicates that HEMA applied to dentinal substrates enhances monomer diffusion and entanglement with dentinal components, and facilitates the formation of a "hybrid" layer. PMID- 1521693 TI - A simple model of crack propagation in dental restorations. AB - Although natural teeth often exhibit microcracks, they rarely demonstrate bulk fracture. However, conventional full-crown restorations periodically exhibit failure due to fracture. Presented here is evaluation of a simple model of crack propagation that estimates crack growth during cyclic loading. A finite element model of a premolar tooth provides the tensile stresses adjacent to cusp loading. If the crack propagation rates for natural teeth, porcelain-fused-to-metal crowns and composite crowns are compared with the wear rates of their respective materials as determined in an artificial mouth, it is evident that the low wear rate of composites may predispose them to fracture. Natural teeth disperse occlusal stresses throughout the dentin so that the effect of high occlusal stress is minimized. Porcelain tends to wear the opposing dentition, which reduces areas of high occlusal stress. Composite, however, demonstrates crack propagation rates higher than those of either natural teeth or porcelain. This, in addition to its low wear rate, might predispose the material to fracture. This model should be used only as a qualitative indicator of fracture tendency. The high calculated crack propagation rates in composites may explain the observed clinical failures and microchipping at the area of occlusal contact, as noted in SEM analysis. PMID- 1521694 TI - The relationship between monomer composition and physical properties of light cured opaque resin. AB - Light-cured opaque resins were prepared using four types of monomer liquids and titanium dioxide powder. This study investigated the relationship between the monomer composition and the physical properties of light-cured opaque resin. Depth of cure, KHN, residual monomer eluent, and bond strength between the opaque resin and cobalt-chromium alloy were measured. The physical properties of triethyleneglycol dimethacrylate (TEGDMA)-based compositions were superior to those of methyl methacrylate (MMA)-based compositions. Viscosity of the opaque resin's liquid monomer was enhanced by 1,6-bis(methacryloxy-2 ethoxycarbonylamino)-2,4,4-trimeth ylhexane (UDMA). The TEGDMA-based light-cured opaque resins showed excellent physical properties and may be clinically acceptable in bonding prosthodontic composite to metal frameworks. PMID- 1521695 TI - Determination of thermal properties of impression materials. AB - Residual strains are important for dimensional accuracy of impression materials. When these strains are being calculated, knowledge of thermophysical constants is needed. This paper describes determination of thermal diffusivity, thermal conductivity, specific heat, heat of polymerization rate, and total heat of polymerization. The first two constants mentioned were obtained from an experiment in which transient heat conductivity was studied. The evaluation was based on an analytical solution of this problem. The remaining constants were derived by means of standard differential scanning calorimetry, DSC. Results from accurate, cost-efficient methods are given for three silicones and one polyether. PMID- 1521696 TI - In vitro bond strengths of three current dentin adhesives to primary and permanent teeth. AB - The in vitro shear bond strengths of three chemically different dentin bonding agents were tested between both permanent and deciduous dentin and their respective anterior composite filling materials. The effect of the post-mortem age of the teeth on bond strength was evaluated by comparison of fresh (extracted within 24 h) and old (extracted within 10 d) teeth. The results indicated that these materials bonded more strongly to the dentin of permanent than to deciduous teeth (8.8 +/- 4.9 MN/m2 vs. 6.2 +/- 4.8 MN/m2). The intermaterial comparison indicated that the bonds to dentin were strongest for Scotchbond 2 (12.3 +/- 4.4 MN/m2) followed by Tenure (6.9 +/- 3.3 MN/m2) and then Gluma (3.3 +/- 1.7 MM/m2). Both the above findings were shown to be statistically significant. The effect of time lapse after extraction of the teeth was not statistically significant. PMID- 1521697 TI - The formation and properties of metal oxide poly(vinylphosphonic acid) cements. AB - Aqueous solutions of poly(vinylphosphonic acid) have been found to form polyelectrolyte cements with a wide range of metal oxides. Poly(vinylphosphonic acid), PVPA, has a structure similar to that of poly(acrylic acid), PAA, but contains pendant phosphonic acid,--P(O)(OH)2, groups in place of the carboxylic acid,--COOH, groups of the zinc polycarboxylate, and glass polyalkenoate cements. It is a stronger acid than PAA, with a greatly increased reactivity toward metal oxides. The physical and mechanical properties of a number of metal oxide PVPA cements were studied and compared with those of zinc polycarboxylate cements. The faster acting of the metal oxide PVPA cement seems to produce a cement that is less susceptible to early hydrolysis. PMID- 1521698 TI - Microstructures of admixed amalgams produced from Pd-containing dispersants. AB - Blended Pd-containing dental amalgams were developed by substituting Pd for up to 20 w/o Ag or Cu in the Ag-Cu eutectic alloy. Melted ingots were lathe-comminuted to a particle size distribution of 1-45 microns. Alloy blends were created from two parts of a traditional amalgam and one part of experimental Ag-Cu-Pd particles. Amalgams with from 0.42 to 1.67 w/o Pd were fabricated by trituration of alloys and mercury at a Hg/alloy ratio of 1:1 with a mechanical triturator at 5000 rpm for 10 s and hand-condensed. XRD studies of these amalgams revealed the suppression of eta' (Cu6Sn5) phase with Pd addition and no gamma 2 (Sn8Hg) phase found. At 3.3 w/o Pd, the eta' (Cu6Sn5) concentration of the amalgam was below the detection limit of the instrumentation (1%). SEM micrographs revealed that reaction zones around eutectic particles decreased with increased Pd concentration. PMID- 1521699 TI - Casting system effectiveness--measurement and theory. AB - Evaluating castability as a property of dental casting alloys is an unworkable concept, since any measure is demonstrably affected by several external factors. Casting System Effectiveness (CSE) is shown experimentally and theoretically to depend primarily upon the time taken for the advancing front to freeze. A spiral tube mold was used to measure casting length obtained under variations in casting temperature; this pattern is proposed as a standard measure of CSE. A Bernoulli 'free-fall' numerical model is shown to reproduce the principal features of such casting, with some evidence of viscosity limitation of the turbulent flow at long casting lengths. Direct measurement of melt velocities confirmed turbulent flow in the mold. A method is also suggested for assessing the influence of investment porosity on CSE. PMID- 1521700 TI - Strengthening of porcelain by ion exchange subsequent to thermal tempering. AB - The purpose of this study was to test the hypothesis that high-leucite content feldspathic porcelain can be strengthened best by thermal tempering followed by ion exchange, compared with either thermal tempering or ion exchange alone. The results of biaxial flexure testing indicate that thermal tempering was the most effective way of strengthening the porcelain among the three methods tested. The combined procedure did not yield the greatest strengthening effect as hypothesized, but one that is only slightly stronger than that produced by ion exchange alone. Weibull analysis indicated that the ion-exchange treatment resulted in a narrower distribution of biaxial flexural strength compared with that of untreated or thermally tempered porcelain. The narrower distribution of biaxial flexural strength is considered desirable for enhancing the longevity of ceramic-based dental restorations. PMID- 1521701 TI - The effect of cross-linking chain length on mechanical properties of a dough molded poly(methylmethacrylate) resin. AB - Three different cross-linking agents which provide a range of cross-linking chain lengths and flexibilities were added to the monomer component of a dough-molded poly(methylmethacrylate) resin in various concentrations, and their effects on the impact strength, transverse bend strength, and tensile strength of the cured polymer were investigated. Increase in the chain lengths of cross-linking agents led to a decrease in the properties of transverse bend strength and tensile strength and an increase in the property of impact strength. PMID- 1521703 TI - Gamma-1 to beta-1 phase transformation in retrieved clinical amalgam restorations. AB - A number of important reactions occur in clinical amalgam restorations. This investigation examined the extent of the gamma-1 to beta-1 transformation in a variety of amalgam restorations retrieved from clinical trials. Sixteen restorations of five brands of low Cu amalgams, 28 restorations of four brands of high Cu blended amalgams, and eight restorations of three brands of high Cu single particle amalgams were studied. The extent of the gamma-1 to beta-1 transformation was determined by the ratio of the integrated intensity of the 002 beta-1 peak to the 330 gamma-1 peak in x-ray diffraction patterns. These values were correlated with age, marginal deterioration grade, and residual Hg content. Restorations consistently contained more beta-1 than comparable laboratory controls. Blended high Cu amalgams generally contained more beta-1, which was correlated with better marginal grades. Beta-1 content was inversely related to residual Hg content. No other associations could be established. A model of the complex interactions between corrosion and transformations was developed. PMID- 1521704 TI - Frictional coefficients of ion-implanted alumina against ion-implanted beta titanium in the low load, low velocity, single pass regime. AB - The frictional coefficients were measured for four wire alloys against the flats of polycrystalline alumina cylinders using a low load, low velocity, single pass device. Ion-implantations of titanium into polycrystalline alumina flats and nitrogen into beta-titanium wires reduced the static and kinetic coefficients from 0.50 and 0.44 before implantation to 0.20 and 0.25 after implantation, respectively. These results are similar in magnitude to frictional coefficients for unimplanted, control couples of stainless steel, cobalt-chromium, and nickel titanium wires against polycrystalline alumina flats. For orthodontic applications, we conclude that more efficient and reproducible appliances can be engineered for tooth movement if ion-implantation is used to reduce the abrasion of beta-titanium by polycrystalline alumina. PMID- 1521702 TI - Bond strength of composite to porcelain treated with new porcelain repair agents. AB - In vitro tensile bond strengths of composite to porcelain were evaluated using three pretreatments (HF etching, sandblasting, diamond abrasion) of the porcelain, four bonding agents (Clearfil Porcelain Bond, Porcelain Liner M, Porcelain Liner M with Super-Bond C&B, and Scotchprime) and two storage conditions (24 h and thermocycling). The overall coefficient of variation was 27%. Significant differences among bond strengths were observed, with storage condition being the most important factor, followed by bonding agent and then pretreatment. Thermocycling decreased the bond strength of all samples, but samples treated with Scotchprime were affected least. For 24 h storage, Clearfil Porcelain Bond and Scotchprime had bond strengths above 23 MN/m2 to sandblasted porcelain. PMID- 1521705 TI - Effect of 4-MET on bond strength and penetration of monomers into enamel. AB - The effect of 4-[2-(methacryloyloxy)ethoxycarbonyl]phthalic acid (4-MET) in self curing acrylic resin initiated by BPO-amine on the bond strength to etched enamel was studied. Scanning electron microscopic (SEM) observations of resin-enamel interfaces were carried out to elucidate the bonding mechanism and the effect of 4-MET on the adhesion. 4-MET, which has both hydrophilic and hydrophobic groups, increased the bond strength of self-curing acrylic resin to etched enamel and improved the bonding stability. SEM pictures strongly suggested that 4-MET promoted interpenetration of monomers into enamel prism peripheries and their polymerization therein resulted in excellent adhesion to etched enamel. PMID- 1521706 TI - Quantitation of total mercury vapor released during dental procedures. AB - An in vitro method is described in which measurements were made of the total amount of mercury vapor released from three types of amalgam during routine dental procedures. It was found that the greatest amount of mercury was released during dry polishing of one amalgam (44 micrograms). Removal of amalgam from a Class I cavity under water spray and high volume evacuation also generated large amounts of mercury as expected (15-20 micrograms). However, under the more clinically relevant conditions of extending evacuation for one minute to remove residual amalgam and mercury after cutting, this value was reduced by approximately 90%. The total amount of mercury generated during placement (6-8 micrograms), wet polishing (2-4 micrograms) and trituration (1-2 micrograms) were also measured. The study showed that dental procedures associated with amalgam do potentially expose the patient and operator to mercury vapor. However, the total amount of mercury released during any procedure was far below the total exposure level calculated from the daily threshold limits established by regulatory agencies for occupational exposure. PMID- 1521707 TI - The effect of thermocycling in microleakage analysis. AB - The purpose of this study was to evaluate the effect of thermocycling on dye penetration during in vitro microleakage analysis of composites. Fifty non carious human molars, stored in 75% ethanol, were divided into five groups (N = 10). Each tooth was prepared for a MOD slot preparation using a high speed handpiece and water, one proximal cervical margin in cementum, the other in enamel. The enamel margins were etched, rinsed, dried, and the composite inserted and cured in multiple increments. Group A was not thermocycled (TC) and was immersed in 0.5% basic fuchsin dye for 24 h at 37 degrees +/- 1 degrees C. Group A' was not TC and was immersed in 0.5% basic fuchsin dye for 4 h at 37 degrees +/ 1 degree C. Group B was TC in a water bath and immersed in dye as with Group A, Group B' was TC and immersed in dye as in Group A'. Group C was TC, as in Group B, but in a basic fuchsin dye bath. Thermocycling consisted of 250 cycles, 15 s dwell time each in 5 degrees C and 50 degrees C bath. The teeth were mounted in acrylic, and multiple cross-sections of all surfaces were prepared. Dye penetration was read on a scale of 0 (no leakage) to 4 (leakage to the pulpal floor) and means calculated for each surface and tooth. There was no significant increase of microleakage in restorations when thermocycling was used to simulate temperature extremes, either in dye or water baths, as opposed to restorations which were not thermocycled. PMID- 1521708 TI - Degradation of microfilled posterior composite. AB - The substantial improvement in the chemical, physical and mechanical characteristics of posterior composites has contributed to their increased use in recent years. However, some troubling characteristics of these materials are their susceptibility to wear, marginal leakage, and recurrent caries. Numerous studies have dealt with the wear resistance of posterior composites. Only a few have investigated the mechanisms of failure, particularly those containing submicron-sized fillers. The purpose of this study, therefore, was to analyze the clinical characteristics of a posterior composite to determine the mechanisms responsible for marginal degradation. Using a series of optical standards, it was determined that the generalized wear-rate was linear, averaging 8 microns/year. Furthermore, it was shown that the marginal defect was cohesive in nature and that this type of defect, which is inherent in submicron-type posterior composites, was probably due to tensile fatigue failure. PMID- 1521709 TI - Effects of palladium addition on properties of dental amalgams. AB - Palladium-containing amalgam alloys were developed utilizing the atomization method. Single-compositional type alloys were fabricated and palladium was substituted for silver in concentrations up to 5 w/o. Alloy powder with a particle size of less than 45 microns was collected and triturated with mercury. Creep, compressive strength and dimensional change tests were performed according to ADA Specification No. 1 along with controls of Tytin, Valiant and Valiant Ph.D. Values for creep decreased and compressive strength increased markedly with additions of palladium. Current densities of the experimental amalgams containing palladium were determined to be an order of magnitude less than the original amalgams in the electrochemical test. A trend of positive relationships between properties and palladium additions was indicated. PMID- 1521710 TI - Treatment of composite surfaces for indirect bonding. AB - Composite can be cured extraorally to fabricate indirect or direct/indirect restorations. These restorations are bonded to the tooth with a dual-cure resin cement. This study evaluated various methods for treating the surface of an indirect glass-filled composite to improve its bond to enamel. The methods tested were air abrasion (sandblasting), hydrofluoric (HF) acid etching, silanation, and combinations of these techniques. Shear bond strengths were measured for thermocycled and non-thermocycled specimens. Air abrasion, followed by silanation, provided the strongest and most consistent bonds. Etching with 9.6% HF gel decreased the bond strengths obtained by air abrasion. HF alone produced the weakest bonds, with most failures occurring adhesively between the indirect composite and the resin cement. PMID- 1521711 TI - The effect of glaze on porcelain strength. AB - The self-glazing technique provides an esthetic and hygienic surface for crowns and fixed partial dentures that use porcelain veneers. A study of the biaxial flexure strengths of polished vs. glazed specimens is needed to verify that current laboratory methods are appropriate for planned fatigue studies. Four groups of 50 porcelain disk specimens each were subjected to the following polishing and firing procedures: group one was fired, glazed-no hold, and polished; group two was fired, polished, and glazed-no hold; group three was fired, polished and glazed-1 min. hold; group four was fired, polished, and not glazed. The piston-on-three-ball method was used for testing biaxial flexure strengths. Significantly lower differences in biaxial flexure strengths were noted when group two values were compared with values from groups one, three and four. The results show that the Weibull distribution is an appropriate model for our studies. Differences in glaze thickness among the groups were noted in SEM examination; however, bulk (interior) microcrack density differences were absent. The specimens that were fired, polished to a 1 micron surface finish, and not glazed (group four) were significantly higher in flexure strength than groups one and three at the p less than 0.001 level. The hypothesis that glazing of porcelain surfaces improves the biaxial flexure strength of test specimens was rejected. PMID- 1521712 TI - The plane of fracture and shear bond strength of three composite inlay systems. AB - Composite inlays have been introduced to overcome some of the problems encountered with direct placement techniques. However, some doubt has been expressed about the strength of the bond between the inlay surface and the composite luting cement due to the decreased number of C = C bonds remaining following supercuring of the inlay. This study investigated the bond strength of three composite inlay systems to etched bovine enamel and recorded the plane of fracture of the samples. The bond strength of one system was significantly greater than that of the other groups and was increased by the application of an unfilled resin enamel bonding agent. Unfilled resin application did not significantly alter the other systems tested. In only one of the systems tested was the inlay/composite cement bond found to be the weak link in the bonding procedure. In this group, the application of the manufacturer's specially formulated bond enhancer did not lead to an increase in bond strength. PMID- 1521713 TI - Gastric fundic epithelial proliferation after pancreaticobiliary diversion. Studies with quantitative histological analysis and autoradiography in the hamster. AB - The effect of pancreaticobiliary diversion (PBD) with hypercholecystokininemia on the gastric fundic mucosa was studied in the Syrian golden hamster over 5 and 24 days. Sham-operated animals served as controls. Basal plasma gastrin concentrations were significantly decreased on days 5 and 24. Five days after PBD, there was a significant increase in the scintigraphically measured [3H] thymidine incorporation into fundic tissue. Correspondingly, there was a significant increase in the number of cells with [3H]-thymidine-labeled DNA in the proliferative zone of the fundic mucosa. The total number of cells in the gastric pits, the number of cells in the proliferative zone and the proliferation index were also significantly increased 5 days after PBD. Although the mean values of all variables were higher after PBD than in the control group on day 24, these increases were not significant. It is concluded that PBD at least transiently stimulates gastric fundic epithelial proliferation in the hamster. Whether this is an effect of hypercholecystokininemia remains to be definitely proven in further studies. PMID- 1521714 TI - The drug 5-aminosalicylic acid rescues alpha 1-proteinase inhibitor from the neutrophil oxidative inactivation. A possible contribution to its therapeutic action in ulcerative colitis. AB - The glycoprotein alpha 1-proteinase inhibitor is the specific inhibitor of neutrophil elastase, a major tissue-damaging protease. When incubated with activated neutrophils, alpha 1-proteinase inhibitor lost its pancreatic porcine elastase inhibitory capacity and became incapable of forming a sodium dodecyl sulphate-stable complex with pancreatic porcine elastase. Inhibitors and scavengers of neutrophil-derived reactive oxygen species outlined the crucial role of hypochlorous acid in the alpha 1-proteinase inhibitor inactivation. Moreover, the drug 5-aminosalicylic acid prevented the inactivation of alpha 1 proteinase inhibitor by neutrophils in a dose-dependent manner. Finally, when the capacity of 5-aminosalicylic acid to rescue alpha 1-proteinase inhibitor from the neutrophil-derived attack was plotted as a function of the 5-aminosalicylic acid ability to scavenge neutrophil-derived hypochlorous acid, a positive linear relationship was found. Thus, our results provide a direct evidence that 5 aminosalicylic acid is able to prevent the oxidative inactivation of alpha 1 proteinase inhibitor by neutrophils. Therefore, we suggest that the drug has the potential to limit the elastase-mediated damage of colonic connective tissue by creating a microenvironment of active alpha 1-proteinase inhibitor around the neutrophils. PMID- 1521716 TI - pH fluctuations versus reflux episodes in patients with gastroesophageal reflux disease: their optimal thresholds and significance in diagnosis. AB - In physiological and pathological conditions, pH monitoring in the esophagus shows small variations as well as more pronounced deflections. However, only the latter are traditionally taken into account in 24-hour pH monitoring analysis. The present study was designed to establish optimal thresholds of pH fluctuations versus reflux episodes in separating physiological and pathological gastroesophageal reflux (GER) and to evaluate their significance in the diagnosis. Twenty-four-hour intraesophageal pH monitoring and endoscopy were performed in 62 patients with GER symptoms and in 42 healthy controls. The results showed that the percentages of the time with pH fluctuations in patients with and without esophagitis and in healthy controls were, on average, 12.65, 9.5 and 2.76% in 24 h, respectively, and the respective percentages of the time with reflux episodes in the same groups in 24 h were, on average, 3.12, 2.04 and 0.18%, respectively. Using a receiver-operating-characteristic curve analysis, less than 6.7% of the time with pH fluctuations and less than 0.1% of the time with reflux episodes were defined as the combined thresholds for physiological versus pathological reflux. The sensitivity of the combined thresholds for the detection of GER patients with and without esophagitis was 96.7 and 90%, respectively, and their specificity for the diagnosis of patients with abnormal GER was 100%. It is concluded that pH fluctuations and reflux episodes, when evaluated together, are more useful for classifying patients with GER and their combined thresholds yield higher diagnostic accuracy in assessing patients with gastroesophageal disease. PMID- 1521715 TI - Cell-kinetic alterations induced by aspirin in human gastric mucosa and their prevention by a cytoprotective agent. AB - The effect on gastric epithelial cell proliferation of a short-term, low-dose treatment with aspirin was evaluated in 9 healthy volunteers. Nine days before and during aspirin administration, the subjects assumed sulglycotide, a sulfated glycopeptide with cytoprotective properties. Endoscopic biopsies were collected in each subject from the gastric body and antrum before and after treatment. The specimens were incubated in a culture medium containing bromodeoxyuridine (BrdU). The proliferative activity was evaluated by immunohistochemical detection of BrdU uptake. A decrease in BrdU-labelled cells together with a shortening of the length of gastric columns were observed after treatment with aspirin and placebo in biopsies of both body and antrum (p less than 0.05). On the contrary, no modifications were observed after treatment with aspirin and sulglycotide. We conclude that a decrease in the proliferative activity of the epithelial cells could be one of the mechanisms by which aspirin affects the defensive properties of gastric mucosa. The treatment with a cytoprotective drug seems to be effective in preventing this alteration. PMID- 1521717 TI - Disability and need for rehabilitation among patients with inflammatory bowel disease. AB - Physicians who manage patients with inflammatory bowel disease (IBD) as well as the patients themselves need to know about the prospects of disability and the demand for rehabilitation associated with this chronic disease. The present study uses German social security statistics to characterize IBD patients undergoing a rehabilitation or having a disability and their employment status before and after rehabilitation. Each year, about 9 and 3% of all German employees with IBD underwent a rehabilitation or were granted a disability pension, respectively. In comparison with other diseases, IBD patients tended to be young, female and employed in white-collar occupations. Although they had significantly longer sick leaves, 87% were still employed before entering rehabilitation. The majority, i.e. 72%, improved under rehabilitation. Compared with other diseases, however, rehabilitation of patients with IBD was less successful, i.e. less patients improved, and more patients remained unchanged or even worsened during rehabilitation. After rehabilitation, continuation of the last employment was recommended in 82% of the cases, in 94% after additional medical or vocational measures. Overall, failed rehabilitation led to a similar rate of disability in IBD as in other diseases. Within the IBD population, however, female sex and white-collar occupations were associated with an increased risk, while male sex and blue-collar occupations were associated with a reduced risk for disability. These data reflect the underlying epidemiology of IBD as well as its natural history. Despite its severity and chronicity, the overwhelming majority of patients with IBD manage to stay in the work force and succeed in overcoming the obstacles posed by their disease. PMID- 1521718 TI - Inhibitory effects of pravastatin, a competitive inhibitor of hydroxymethylglutaryl coenzyme A reductase, on cholesterol gallstone formation in prairie dogs. AB - The effects of pravastatin on cholesterol gallstone formation were determined in prairie dogs. We fed 10 prairie dogs 1% cholesterol with or without 0.05% (w/w) pravastatin (n = 5, each) for 4 weeks. In addition, another 5 prairie dogs were fed a standard rodent chow as a control. Only the animals fed 1% cholesterol without pravastatin treatment formed cholesterol gallstones. Gallbladder bile from cholesterol-fed animals contained cholesterol monohydrate crystals, whereas those treated with pravastatin contained no crystal. Furthermore, marked increases in tissue cholesterol levels (serum, liver and bile), and in biliary mucous glycoprotein levels were evident in cholesterol-fed animals, whereas pravastatin treatment normalized these levels. These findings raise the possibility that such inhibitors might have a future role to play in the prevention of cholesterol gallstone formation and/or recurrence. PMID- 1521719 TI - Maternal insulin treatment improves pre-implantation embryo development in diabetic rats. AB - Pre-implantation embryos were recovered from control, diabetic and insulin treated diabetic rats on day 5 of pregnancy. Compared to control animals, diabetic rats had a 20% reduction in the number of embryos per rat and blastocysts recovered from diabetic rats showed a 19% decrease in total cell number. The cellular decrease observed in blastocysts was mainly at the expense of the inner cell mass. Insulin replacement therapy was started on day 1 of pregnancy and normalized the glycaemia of diabetic rats but failed to raise the number of embryos per rat toward the control value. Insulin treatment, however, fully restored the normal cell number in both the inner cell mass and trophectoderm of blastocysts. The dead cell index, which was significantly elevated in the inner cell mass of blastocysts from diabetic rats, also returned to the control value following insulin treatment. Our data suggest that diabetes induced impairment of pre-implantation development can be partly prevented by insulin treatment started shortly after conception. PMID- 1521720 TI - Cytotoxic effects of cytokines on rat islets: evidence for involvement of free radicals and lipid peroxidation. AB - We have previously reported that oxygen free radical scavengers protect rat islet cells from damage by cytokines and we interpreted these findings as suggesting the involvement of oxygen free radicals but did not directly measure indices of free radical activity. In this study, we report on malondialdehyde, an end product of lipid peroxidation, in rat islets incubated with cytokines. The individual cytokines, interleukin 1 (1 U/ml), tumour necrosis factor (10(2) U/ml), and interferon gamma (10(2) U/ml) inhibited insulin release but did not increase islet malondialdehyde levels. Combination of these cytokines however, produced significant increases in islet malondialdehyde and this was accompanied by islet necrosis. Furthermore, an inhibitor of lipid peroxidation, U78518E, significantly decreased the cytokine-induced increase in islet malondialdehyde and protected islet Beta cells from destruction by the cytokine combination of interleukin 1, tumour necrosis factor and interferon gamma. These findings suggest that the cytotoxic action of cytokines on islet Beta cells may result from free radical production and lipid peroxidation in the islet cells. PMID- 1521721 TI - Sorbinil does not prevent hyperfiltration, elevated ultrafiltration pressure and albuminuria in streptozotocin-diabetic rats. AB - The effects of aldose reductase inhibition on kidney function were studied in rats with streptozotocin-induced diabetes mellitus. Diabetic rats were fed sorbinil (20 and 50 mg/kg) by daily gastric gavage and were compared with untreated diabetic rats and normal rats. The rats were under daily supervision with regard to blood glucose control, insulin administration and body weight. The aim was to promote continuous body growth and to maintain the blood glucose concentration at around 22 mmol/l without large day-to-day fluctuations. The renal functional changes observed in this well-established diabetic model closely resembled those reported in human Type 1 (insulin-dependent) diabetes mellitus. Sorbinil treatment completely prevented renal cortical sorbital accumulation, but did not abolish kidney enlargement or the increase in ultrafiltration pressure and glomerular filtration rate. Albumin excretion was increased to the same extent in the sorbinil-treated and in the untreated diabetic rats. We conclude that increased metabolism of glucose to sorbitol does not cause the hyperfiltration in rats with streptozotocin-induced diabetes. PMID- 1521722 TI - Genetic analysis of HLA class II alleles and susceptibility to type 1 (insulin dependent) diabetes mellitus in Japanese subjects. AB - Although HLA-DQB1 alleles encoding aspartic acid at position 57 (Asp-57) are protective against Type 1 (insulin-dependent) diabetes mellitus in Caucasians, most Japanese Type 1 diabetic patients carry at least one Asp-57 DQB1 allele. We analysed the DRB1, DQA1 and DQB1 genes of 99 Japanese patients and 86 control subjects with polymerase chain reaction and sequence-specific oligonucleotide hybridization. We found that (1) the DQA1*0301 allele was significantly increased in Type 1 diabetic patients (RR7.8, pc less than 0.0001); (2) the DRB1*0405 (Dw15) allele, which is a subtype of DR4 haplotype, was significantly increased in DR4-positive patients (RR 12.0, pc less than 0.001); and (3) although the DRw8 DQw8 haplotype was positively associated with Type 1 diabetes, the DRB1*0406-DQw8 haplotype was decreased in the diabetic patients. These data indicate that DRB1 and DQA1 genes also confer susceptibility to Type 1 diabetes in Japanese. PMID- 1521723 TI - Mechanical load on the inspiratory muscles during exercise hyperpnea in patients with type 1 (insulin-dependent) diabetes mellitus. AB - The aim of this study was to evaluate the difference between Type 1 (insulin dependent) diabetic patients and healthy control subjects regarding inspiratory muscle load during exercise hypernea. For this purpose an incremental progressive exercise test on a cycle ergometer was performed by 36 Type 1 diabetic patients and 40 healthy subjects. In order to determine the mechanical load on the inspiratory muscles breath by breath, we selected the following two parameters, which represent the pressure generated by the inspiratory muscles as well as the duration and velocity of their contraction: (1) the oesophageal tension time index, which is the product of the duty cycle (ratio of inspiratory time to total breath cycle duration) and the mean oesophageal pressure expressed as a percentage of the maximal oesophageal pressure and (2) the mean oesophageal pressure change per time unit during the inspiratory phase of each breathing manoeuver, which is expressed as a fraction of the subject's maximal oesophageal pressure. Comparison of the two groups revealed that at similar levels of ventilation the mechanical load on the inspiratory muscles was significantly higher in the Type 1 diabetic patients than in the control subjects. When the loading was stopped the maximal ventilation was lower in the patients. Nevertheless, they reported a degree of respiratory effort sensation comparable to the control group, which seems to have been caused by an increase of the mechanical load on the ventilatory muscles. PMID- 1521724 TI - Quality assessment of diabetes care according to the recommendations of the St. Vincent Declaration: a population-based study in a rural area of Austria. AB - Using a mobile ambulance the quality of diabetes care was evaluated, according to the recommendations of the St. Vincent Declaration, in 95% of all known diabetic patients (n = 395) in a geographically defined rural area of Austria with 7871 inhabitants. Fourteen of the 395 patients had Type 1 (insulin-dependent) diabetes with age at onset of diabetes below 30 years. Of the 375 patients examined (women 61%, age 66 +/- 13 years, median diabetes duration 6 years) 16% were treated with insulin and 47% with oral agents; HbA1c levels were 7.3 +/- 1.7%. Prevalence of known hypertension was 54%; 68% of these patients had their blood pressure uncontrolled (systolic greater than or equal to 160 and/or diastolic greater than or equal to 95 mmHg); a further 15% of patients with previously unknown hypertension had blood pressure values of greater than or equal to 160 and/or greater than or equal to 95 mmHg. Urinary albumin concentrations of greater than 200 mg/l were found in 15% of patients, 2% had a serum creatinine level of greater than 177 mumol/l, no patient had renal replacement therapy. Six patients (1.5%) were blind. Screening for retinopathy identified six patients (out of 317 in whom the retina could be evaluated) for whom consultation with an ophthalmologist as soon as possible was recommended. Of the total patient group (n = 395) 20 patients (5%) had foot complications (amputations and/or ulcers): 14 patients had a total of 21 lower limb amputations (eight above knee, six below knee, seven below ankle); eight of these 14 patients lived in a nursing home; 11 patients had a total of 13 foot ulcers.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1521726 TI - The relation of fetal growth to plasma glucose in young men. AB - In a study of men aged 59 to 70 years plasma glucose levels 30 min and 2 h after a 75-g glucose load were inversely related to birthweight. To determine whether there are similar relations at a younger age the 30-min plasma glucose levels of 40 men aged 21 years, who were born in one hospital in the United Kingdom, were measured. Lower birthweight was associated with higher 30-min plasma glucose levels. This trend was independent of gestational age, and current body mass, height and social class. PMID- 1521725 TI - Enrichment of beta cells from the human fetal pancreas by fluorescence activated cell sorting with a new monoclonal antibody. AB - The aim of this study was to produce an antibody reactive to the surface of endocrine pancreatic cells and use this antibody for the purification of endocrine cells from the human fetal pancreas by fluorescence activated cell sorting. We describe such an antibody, called N1, reacting with the surface and cytoplasm of endocrine cells in the adult and fetal human pancreas (12 to 18 weeks gestational age). While unreactive to exocrine and mesenchymal cells, it was not specific for endocrine cells, as evidenced by its staining pattern in tissues other than pancreas. Almost 40% of the N1-positive pancreatic cells contained either insulin, glucagon or somatostatin. Conversely, more than 90% of each of the hormone-containing cells was N1 positive. An additional 40% of N1 positive cells, not containing other pancreatic hormones, was shown to contain islet amyloid polypeptide, synaptophysin, chromogranin, tyrosine hydroxylase or CA812. A two-step collagenase digestion protocol yielded 1.29 +/- 0.17 x 10(5) cells per mg pancreatic tissue. After Percoll gradient centrifugation, the suspension contained 15.6 +/- 5.7% (n = 25, mean +/- SD) cells reactive with N1. By fluorescence activated cell sorting using the antibody N1, the single-cell suspension was enriched from 3.0 +/- 1.4% to 16.2 +/- 4.8% (n = 10, p less than 0.01) Beta cells. Alpha and Delta cells were also enriched significantly by this procedure. The percentage of N1-positive cells increased from 17 +/- 4% to 83 +/- 6%. This preparation enriched for endocrine cells allows future studies on possible endocrine precursor cells. PMID- 1521728 TI - Power spectral analysis of the electrocardiogram in diabetic children. AB - In recent years it has been shown that alteration in heart rate variability can be used for the objective assessment of autonomic function in adult diabetic patients. Using a microcomputer based system for on-line monitoring and analysis of heart rate variability by power spectral analysis, 100 children with Type 1 (insulin-dependent) diabetes mellitus were studied. A highly significant negative correlation was identified between heart rate variability and duration of diabetes (r = -0.88, p less than 0.0001). The mean heart rate variability in patients with diabetes of duration 3 years or more was significantly lower in comparison to age-matched control subjects. A highly significant negative correlation was evident between heart rate variability and mean HbA1 in patients with duration of diabetes of 5 years or more. A mean HbA1 over 10% during this period was associated with the greatest reduction in heart rate variability. Serial measurements of heart rate variability in diabetic children may be of predictive value prior to the onset of symptomatic neuropathy. PMID- 1521727 TI - Plasma lipoproteins and renal function during simvastatin treatment in diabetic nephropathy. AB - The aim of this study was to assess the effect of simvastatin on plasma lipoproteins and renal function in hypercholesterolaemic Type 1 (insulin dependent) diabetic patients with diabetic nephropathy. Twenty-six hypercholesterolaemic (total cholesterol greater than or equal to 5.5 mmol/l) Type 1 diabetic patients with nephropathy were enrolled in a double-blind randomized placebo-controlled study for 12 weeks. The active treatment group (n = 14) received simvastatin (10-20 mg/day) for 12 weeks while the remaining 12 patients received treatment with placebo. The results during simvastatin treatment (baseline vs 12 weeks): total cholesterol 6.6 vs 4.8 mmol/l (p less than 0.01), LDL-cholesterol 4.25 vs 2.57 mmol/l (p less than 0.01) and apolipoprotein B 1.37 vs 1.06 mmol/l (p less than 0.01). HDL-cholesterol, and apolipoprotein A-I remained unchanged. Total cholesterol, LDL-cholesterol, HDL cholesterol, apolipoprotein A-I, apolipoprotein B remained unchanged during placebo treatment. Albuminuria measured during the simvastatin and the placebo treatment (baseline vs 12 weeks) (the data are logarithmically transformed before analysis because of their positively skewed transformation; geometric mean (x/divided by antilog SE) is indicated) was 458 (x/divided by 1.58) vs 393 (x/divided by 1.61) and 481 (x/divided by 1.62) vs 368 (x/divided by 1.78 micrograms/min (NS). Glomerular filtration rate during simvastatin and placebo treatment (baseline vs 12 weeks) was 64 vs 63 and 72 vs 74 ml.min-1.1.73 m-2, respectively. Two patients receiving simvastatin treatment were withdrawn, one due to gastrointestinal side effects and one due to myalgia.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1521729 TI - Body fat distribution and coronary heart disease mortality in subjects with impaired glucose tolerance or diabetes mellitus: the Paris Prospective Study, 15 year follow-up. AB - The Paris Prospective Study is a long-term, large-scale study of the factors predicting coronary heart disease in healthy middle-aged men. Subjects with impaired glucose tolerance or diabetes (not treated by insulin) at the first follow-up examination (n = 973) were selected from the total cohort for a separate analysis of the predictors of death from coronary heart disease. An index of body fat distribution, the iliac to thigh ratio, was entered into the list of potentially predictive variables, despite the fact that it had been measured one year before the first follow-up examination. After 15 years of mean follow-up, 41 of the selected subjects had died from coronary heart disease. Univariate analysis showed that these subjects differed from the subjects who died of another cause or who were alive at 15 years on the following variables: iliac to thigh ratio (p less than 0.0005), plasma triglyceride level (p less than 0.006), systolic blood pressure (p less than 0.01), and body mass index (p less than 0.04). In multivariate regression analysis using the Cox model, only iliac to thigh ratio and triglyceride plasma level achieved statistical significance as independent predictors. This result supports the current hypothesis that upper body fat distribution, a characteristic trait of subjects with diabetes of glucose intolerance, plays an important role towards their high cardiovascular risk. However, it is unlikely that this role would be mediated through the lipid abnormalities that have been described as associated with upper-body fat deposition. PMID- 1521730 TI - Immunoradiometric assay of insulin, intact proinsulin and 32-33 split proinsulin and radioimmunoassay of insulin in diet-treated type 2 (non-insulin-dependent) diabetic subjects. AB - Plasma insulin, intact proinsulin and 32-33 split proinsulin measured by specific immunoradiometric assays and insulin and C-peptide measured by radioimmunoassay were measured during a constant infusion of glucose test in ten diet-treated subjects with a history of Type 2 (non-insulin-dependent) diabetes (termed diabetic subjects), mean fasting plasma glucose 6.0 +/- 1.0 mmol/l (mean +/- SD), and 12 non-diabetic control subjects. Immunoreactive insulin concentrations measured by radioimmunoassay were 33% higher than insulin and 16% higher than the sum of insulin and its precursors by immunoradiometric assay. The diabetic and non-diabetic subjects had similar fasting concentrations of insulin, intact proinsulin and 32-33 split proinsulin. The ratio of fasting intact proinsulin to total insulin was greater in the diabetic than the non-diabetic group 12.0% (6.8 21.0%, 1 SD range) and 6.3% (4.0-9.8%), respectively, p less than 0.01), though the groups overlapped substantially. After glucose infusion, diabetic and non diabetic subjects had similar intact proinsulin concentrations (geometric mean 4.9 and 5.2 pmol/l, respectively), but the diabetic group had impaired insulin secretion by immunoradiometric assay (geometric means 55 and 101 pmol/l, p less than 0.05) or by radioimmunoassay C-peptide (geometric means 935 and 1410 pmol/l, p less than 0.05), though not by radioimmunoassay insulin (87 and 144 pmol/l, p = 0.12), respectively. Individual immunoradiometric assay insulin responses to glucose expressed in terms of obesity were subnormal in nine of ten diabetic subjects. Radioimmunoassay insulin and C-peptide gave less complete discrimination (subnormal responses in six of ten and eight of ten, respectively).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1521731 TI - Insulin receptor and insulin-responsive glucose transporter (GLUT 4) mutations and polymorphisms in a Welsh type 2 (non-insulin-dependent) diabetic population. AB - We have recently examined the exons encoding the insulin receptor tyrosine kinase domain and GLUT 4 in 30 subjects with Type 2 (non-insulin-dependent) diabetes mellitus using a molecular scanning approach. The variant sequences Val-Met985 and Lys-Glu1068 of the insulin receptor and Val-Ile383 of GLUT 4 were each separately found in three different diabetic subjects. In a study of a Welsh population, the GLUT 4(383) variant was found in three of 160 diabetic and none of the 80 control subjects. In this study, the same group of Welsh Type 2 diabetic and control subjects was analysed using allele-specific oligonucleotide hybridisation, single nucleotide primer extension and allele-specific restriction digestion to ascertain the frequency of the two insulin receptor mutations. The Val-Met985 mutation was found in none of the 160 Welsh Caucasian Type 2 diabetic subjects and two of 80 control subjects. The Lys-Glu1068 mutation removes a Sty 1 site and digestion of amplified exon 18 with Sty 1 confirmed the presence of the mutation in the heterozygous state in the original subject. None of the Welsh diabetic or control subjects had the Glu1068 mutation. The discovery of a very common silent polymorphism at codon 130 of GLUT 4 allowed examination of the association of this locus with Type 2 diabetes using allele-specific oligonucleotide hybridisation in a subset of the Welsh subjects.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1521732 TI - Expression of the 64 kDa/glutamic acid decarboxylase rat islet cell autoantigen is influenced by the rate of insulin secretion. AB - This study examined the relationship between insulin secretion and expression of the 64 kDa/glutamic acid decarboxylase autoantigen in pancreatic islets. Islets isolated from Wistar rats were cultured for 3 days under different conditions: in 5.5 mmol/l glucose with or without alpha-ketoisocaproic acid or glipizide and in 28 mmol/l glucose with or without diazoxide. The 64 kDa/glutamic acid decarboxylase autoantigen was precipitated from lysates of [35S]-methionine labelled islets with sera from patients with Type 1 (insulin-dependent) diabetes mellitus and identified by sodium dodecyl sulphate-polyacrylamide gel electrophoresis and fluorography. In parallel, insulin contents of the islets and the media were determined as well as the rates of glucose-stimulated (pro)insulin biosynthesis. alpha-Ketoisocaproic acid and glipizide were found to stimulate the expression of the 64 kDa/glutamic acid decarboxylase autoantigen and also the rate of insulin secretion. Diazoxide on the other hand reduced the rate of the 64 kDa/glutamic acid decarboxylase autoantigen synthesis in parallel with an inhibition of glucose-stimulated insulin release. Under most of the conditions employed, (pro)insulin biosynthesis was not affected. The correlation found between the rate of insulin release and expression of the 64 kDa/glutamic acid decarboxylase autoantigen might provide an explanation for the earlier observed relationship between the functional demands on the Beta cells and their rate of destruction which may result in diabetes. PMID- 1521733 TI - Pancreatic transplantation: why, when and who? PMID- 1521734 TI - Reform of the National Institutes of Health. PMID- 1521735 TI - The disease defense buildup. PMID- 1521736 TI - Control, bioenergetics, and adaptation in health and disease: noninvasive biochemistry from nuclear magnetic resonance. AB - The noninvasive study of cellular homeostasis, control, and energetics in tissues and organs within intact living systems is now possible. Nuclear magnetic resonance (NMR) spectroscopy in vivo provides information about key metabolites, reaction rates, the control of ionic equilibria and fluxes (including that of H+), and molecular diffusion and motions within the cell. When phosphorus (31P) is measured, the processes associated with the production and utilization of adenosine triphosphate (ATP) are followed. Using 13C for measurement, the pathways and fluxes in the synthesis and degradation of sugars (e.g., glycogen), amino acids, etc., can be observed. Intracellular, cytoplasmic pH (H+ concentration) can be determined from the 31P-NMR spectrum of organs and cells whereas Na+ and K+ (or its congener Rb+) are directly measurable by NMR. All these can be observed in physiological situations in almost any organism in the animal or plant kingdom. The bioenergetics of locust muscle in flight is as readily measured as that in human muscle in health, training, and disease. When spatially resolved, the NMR spectra can provide metabolic maps of the human heart, brain, and other organs. Thus we can now directly delineate the biochemical basis of human diseases. PMID- 1521737 TI - Studies of intestinal stem cells using normal, chimeric, and transgenic mice. AB - The mouse intestinal epithelium represents a continuous developmental system. Its four principal differentiated cell types--enterocytes, goblet, enteroendocrine, and Paneth cells--are derived from a common multipotent stem cell located near the base of monoclonal crypts. Members of these four lineages undergo rapid and perpetual renewal along an anatomically well-defined pathway. The gut epithelium provides a unique mammalian model for studying the biological features of stem cells (e.g., their ability to undergo asymmetric division, their enormous proliferative potential, their capacity for functional anchorage in a niche), examining how stem cell hierarchies are established and maintained in renewing cell populations, analyzing the relationships between passage through the cell cycle and lineage allocation (commitment), and defining the mechanisms that give stem cells a "positional address" along the cephalocaudal axis, allowing them to generate regional differences in the differentiation programs of their derived lineages (axial pattern formation). PMID- 1521738 TI - Function of the c-Myc oncoprotein. AB - The c-Myc protein, the product of the c-myc proto-oncogene, is a nuclear phosphoprotein with DNA binding properties. Deregulated c-myc expression participates in the development of experimentally induced tumors, and its expression appears to be abnormal in many naturally occurring malignancies. Although the precise molecular mechanism of c-Myc activity in oncogenesis and in normal cell proliferation is unknown, recent advances have uncovered a series of molecular and cellular properties of c-Myc. These properties include nuclear localization, transcriptional activation, oligomerization nonspecific and specific DNA binding. Recently, the c-Myc protein was found to heterodimerize with Max, a protein that cooperates with c-Myc to bind specifically to a core DNA sequence, CAC(G/A)TG. These characteristics suggest that c-Myc participates in the regulation of gene transcription in normal and neoplastic cells. PMID- 1521739 TI - Electrolyte transport in the epithelium of pulmonary segments of normal and cystic fibrosis lung. AB - The epithelium of pulmonary segments from trachea to aveoli actively transports electrolytes and allows osmotic movement of water to maintain the ionic environment in the airway lumen. Models of airway absorption and secretion depict the operation of transporters localized to apical or basolateral membrane. In many epithelia, a variety of electrolyte transporters operate in different combinations to produce absorption or secretion. This also applies to pulmonary epithelium of the large airways (trachea, main-stem bronchi), bronchioles, and alveoli. Na+ absorption occurs in all three pulmonary segments but by different transporters: apical Na+ channels in large airways and bronchioles; Na+/H+ exchange and Na+ channels in adult alveoli. The Na+ channels in each pulmonary segment share a sensitivity to amiloride, a potent inhibitory of epithelial Na+ channels. Fetal alveoli display spontaneous Cl- secretion, as do the large airways of some mammals, such as dog and bovine trachea. Cl- channels differ in conductance properties and in regulation by intracellular second messengers, osmolarity, and voltage mediate stimulated Cl- secretion. Electroneutral carriers, such as NaCl(K) cotransport, Cl-/HCO3- exchange, and Na+/HCO3- exchange, operate in large airways and alveoli during absorption and secretion. Abnormal ion transport in airways of cystic fibrosis (CF) patients is manifest as a reduced Cl- conductance and increased Na+ conductance. Isolation of the CF gene and identification of its product CFTR now allow investigations into the basic defect. Intrinsic to these investigations is the development of systems to study the function of CFTR and its relation to electrolyte transporters and their regulation. PMID- 1521740 TI - Elevation of lung glutathione by oral supplementation of L-2-oxothiazolidine-4 carboxylate protects against oxygen toxicity in protein-energy malnourished rats. AB - The objectives of this study were to investigate whether oral supplementation of L-2-oxothiazolidine-4-carboxylate (OTC) is effective for increasing tissue glutathione (GSH) concentrations in rats fed a diet very low (0.5%) in protein-a model of wasting malnutrition-and to determine the efficacy of OTC for protection against pulmonary oxygen toxicity. Weanling rats, fed a 0.5 or 15% protein diet for 2 wk, were given an oral supplement of OTC, and tissue GSH concentrations were measured over a 24 h period. OTC supplementation to rats fed 0.5% protein significantly increased GSH concentrations in liver and lung, but not in kidney and blood, when compared with the 0.5% protein unsupplemented group. The liver GSH concentration in the 0.5% protein OTC-supplemented group was higher than the 15% control group. Daily supplementation of OTC protected rats from pulmonary oxygen toxicity during 4 days of 85% oxygen exposure as determined by lung-to body weight ratios and in vivo proton magnetic resonance imaging. Although hyperoxia exposure increased lung GSH concentrations in all groups, OTC supplementation was effective for increasing lung GSH concentration in rats fed the 0.5% protein diet. This study demonstrated that oral administration of OTC to wasting malnourished rats is an effective procedure to increase GSH concentration rapidly in target organs such as lung, and that daily supplementation of a low dose of OTC has a sustained effect to protect against pulmonary oxygen toxicity during 4 days of hyperoxia exposure. PMID- 1521741 TI - A parkinsonian syndrome induced in the goldfish by the neurotoxin MPTP. AB - Parkinson's disease has been modeled in humans, lower primates, and to a lesser extent in some other vertebrates by administration of the potent neurotoxin MPTP (1-methyl-4-phenyl-1,2,3,6 tetrahydropyridine). The MPTP model has thus drawn considerable attention as a system to search for anti-Parkinson's disease drugs, although the cost and scarcity of primates has limited extensive applications. We now report that a parkinsonian syndrome can be elicited in the common goldfish (Carassius auratus) by a single dose of MPTP. The syndrome is characterized by profound bradykinesia (slow movement), the full extent of which is reached 3 days after MPTP administration. The reduction in movement is paralleled by loss of dopamine and norepinephrine from the forebrain and midbrain and in other brain regions as well. The toxic oxidative product of MPTP, MPP+, is also accumulated predominantly in forebrain and midbrain, and pretreatment with the monoamine oxidase blocker tranylcypromine substantially reduces accumulation of the toxic metabolite. A barely perceptible coarseness in balance adjustment also occurs in treated animals. The MPTP-treated goldfish recover normal movement and normal brain monoamine levels within 10-13 days after administration of the drug. We interpret these and other data to indicate that MPTP can induce a Parkinson's disease-like syndrome in the goldfish that is similar in many aspects to the syndrome induced by MPTP in humans and other primates. This remarkable parallel may permit the goldfish to supplement expensive and scarce primates for the purpose of searching and screening neuroprotective drugs with specific relevance to Parkinson's disease. PMID- 1521742 TI - Culture of bovine pulmonary artery endothelial cells on Gelfoam blocks. AB - Conventional methods of endothelial cell culture on monolayers and beads require enzymatic digestion, traumatic scraping, or centrifugation to transfer cells to other experimental systems. Gelfoam, a porous gelatin block, not only supports the growth of bovine pulmonary artery endothelial cells but also allows the rapid transfer of cell-laden blocks from one experimental system to another with minimal intervention. This property has been shown to be especially useful for the rapid fixation of endothelial cells for microscopy using standard histologic methods. Histology confirmed that the trabecular nature of the substrate allows endothelial cells to line the interstices of the sponge matrix and grow in a configuration that simulates the appearance of the endothelium in small vessels and capillaries. The inoculation of 1 x 10(5) endothelial cells on 7.5 mg Gelfoam (24 x 8 x 2 mm blocks) was enhanced by fibroblast growth factor and resulted in cell attachment by day 2 with a cell doubling time of 1.7 days. In addition, endothelial cells completely infiltrated 1, 5 and 7.5 mg Gelfoam blocks, as verified by histology. Assays to quantify cell number and protein were easily performed. To facilitate cell counting, the Gelfoam matrix was rapidly removed by the addition of 0.05 mg/ml collagenase, a concentration that interfered minimally with the assay for cellular protein concentration. The data demonstrate that Gelfoam is a suitable support growth matrix for the in vitro culture of bovine pulmonary artery endothelial cells. PMID- 1521743 TI - Dopa: then and now. PMID- 1521744 TI - [Laughter, humor and medicine]. PMID- 1521745 TI - [Thyroid function tests in healthy and ill elderly]. AB - Thyroid function in the elderly has been a matter of discussion. The universe of the present study includes males and females 36 hospitalized with an average age of 72.97 +/- 8.70 years (group I) and 36 ambulatory asymptomatic elderly with 69.81 +/- 8.55 years of age (group II). Serum levels of T3, T4, T4L and TSH were measured in both groups. Mean values of T3 were significantly lower in the hospitalized patients than in the control group. The difference persisted on both, males and females, analyzed separately. Mean values of T4L were significantly lower in women of group II, while mean values of T3 were significantly lower in men of group I. The comparison of thyroid function tests in male and female showed that serum values of T3 and T4 were significantly lower in men of group I. By dividing results in age categories, serum levels of T4L in group II were significantly lower in the age group of 70 to 79 and 80 to 89. Thyroid function tests in asymptomatic ambulatory elderly tend to be normal, whereas the hospitalized patients showed a high proportion of alterations. PMID- 1521746 TI - [Histologic changes in peptic disease]. AB - The purpose of this work is to describe pathological alterations produced by the gastric juice in esophagus, stomach, duodenum, and small intestine. Histology of these segments of the gastrointestinal tract are briefly explained. Peptic esophagitis, Barrett's esophagus, chronic gastritis, duodenitis, and peptic ulcer in several sites are described. PMID- 1521747 TI - [Usefulness of ultrasonography in the complications of hepatic punction. Prospective studies]. AB - We evaluated the usefulness of ultrasonography (US) to detect hepatic puncture complications. We studied 50 patients, 28 males and 22 females became hepatic puncture. The needles that we used were in 40 Tru-cut in two Chiba in one angiocath and in the other remaining two. US were performed one day before the liver puncture and were repeated 24 to 48 h post-puncture. The procedure was blindly on 29, in fourteen guided by US or scintigraphy, and by laparoscopy in seven. Six patients developed complications (12%), two hemobilia; two subcapsular hematoma, one hemoperitoneum and one hematoma of the abdominal wall. The US detected five of the six complications, and four patients had clinical signs. The sensitivity was 88 percent and the specificity 100%. Platelet count impaired was determinant for the complication. US is useful to detect liver puncture complications. PMID- 1521748 TI - [Rheumatic features of Grave's disease in children]. AB - We report three cases from girls with Graves disease who developed serious rheumatic manifestations. One patient had systemic lupus erythematosus with articular, renal, neurological and cardiac afectation with fatal outcome. Other patient presented clinical features of scleroderma with skin thickness, myopathy, arthritis, Raynaud's phenomenon and findings of pulmonary fibrosis. A lupus-like syndrome associated to methimazole therapy (polyarthritis, rash and hemolytic anemia) with positive Cel-LE preparations but negative antinuclear-antibodies was observed in a third patient. A careful history and the recognition of these manifestations will help in the identification of these syndromes. PMID- 1521749 TI - [Papillary or villous adenoma at the Spanish Hospital of Mexico]. PMID- 1521750 TI - [The metropolitan index of air quality]. PMID- 1521751 TI - [What is the use of the metropolitan index of air quality?]. PMID- 1521752 TI - [Lead poisoning in childhood]. PMID- 1521753 TI - [Genetic disorders in sexual differentiation in humans]. PMID- 1521754 TI - [The influence of psychosocial deprivation and body composition on plasma gonadotrophins in children and adolescents]. AB - The plasma concentrations of FSH and LH were measured in 250 boys with psychosocial deprivation (PSD) aged 9.0-15.9 years and in 357 clinically healthy boys of the same age. The results were correlated with chronological age (CA), weight, height and calculated lean body mass (LBM) and total body fat (TBT). On a group basis, PSD boys had the clinical onset of puberty at 13.9 years, while healthy boys did so at 11.9 years. In both groups, the mean weights at time of initiation of the adolescent growth spurt and time of peak velocity of weight gain were very close to each other and the same phenomenon was true for their heights and the amount of LBM. Based on CA mean plasma FSH concentrations in PSD boys and a steep rise two years later than in healthy boys; however, when analyzed as a function of body weight, height or LBM, no such difference emerged. On the other hand, mean plasma LH concentrations in PSD boys were higher than in healthy boys only up to 12.9 years, 42.9 kg of body weight, a height of 142.0 cms and LBM of 32.0 kg; however, no steep rise in plasma LH was observed in contrast to healthy boys. No correlations was observed between TBF and plasma gonadotropins. Therefore, although on the basis of CA, PSD boys had a delayed onset in plasma gonadotropins changes, this occurred in association with the attainment of similar body weight, height and LBM as in healthy boys.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1521755 TI - [The practice of medicine, the physician and death]. PMID- 1521756 TI - [Death, the cadaveric donor and the obtention of organs for transplantations]. PMID- 1521757 TI - The detection of two antigenic groups among Renibacterium salmoninarum isolates. AB - The analysis of the membrane proteins and their antigenic properties in a group of 14 geographically diverse strains of Renibacterium salmoninarum revealed the existence of antigenic diversity within this species. Eleven isolates, including the type strain ATCC 33209, shared a similar protein profile with a major component of 57 kDa whereas three strains showed a common pattern with a major protein of 30 kDa. The quantitative agglutination tests and Western blotting assays seem to indicate the existence of serological heterogeneity, with two distinct groups being detected. PMID- 1521758 TI - Two forms of ribulose-1,5-bisphosphate carboxylase/oxygenase from Thiobacillus denitrificans. AB - The autotrophic, sulfur-oxidizing bacterium Thiobacillus denitrificans possesses two forms of the Calvin cycle enzyme ribulose-1,5-bisphosphate carboxylase/oxygenase (RuBisCO). The form I and form II genes were isolated from a cosmid library using heterologous DNA probes. Restriction enzyme analysis indicated that the genes are within 17 kbp of each other. Other Calvin cycle enzyme genes are not present. Analysis of T. denitrificans RNA indicated that the form I genes for the large and small subunits are co-transcribed with a length of 2800 nucleotides. The transcript for the form II gene is 1900 nucleotides in length. PMID- 1521759 TI - Characterization of an extracellular factor that stimulates bile salt hydrolase activity in Lactobacillus sp. strain 100-100. AB - Bile salt hydrolase activity in Lactobacillus sp. strain 100-100 is strictly intracellular. The strain produces an extracellular factor that stimulates the intracellular hydrolase activity. The factor is inducible by conjugated bile salts, has an apparent molecular mass over 12 kDa but less than 25 kDa, is stable in air, and resistant to pronase and heat. It is partially extractable into organic solvents and inactivated by a sulphydryl group inhibitor. We postulate that the factor functions by a novel mechanism to facilitate entry of conjugated bile salts into the bacterial cells. PMID- 1521760 TI - Stage-specific proteinases of Leishmania mexicana mexicana promastigotes. AB - Four distinct bands of cysteine proteinase activity were detected when stationary phase populations of Leishmania mexicana mexicana were subjected to gelatin-SDS PAGE. The highest mobility band contained at least three isoforms separable by mono Q anion exchange chromatography. These high mobility activities were distinct from all the major amastigote enzymes. Stationary-phase promastigote populations also contained two acid-activable precursor forms of the promastigote specific band. It is suggested that these promastigote-specific activities occur in the infective metacyclic stage of the parasite and may have a role in parasite survival upon inoculation into a mammal. PMID- 1521761 TI - Improved method for electroporation of Staphylococcus aureus. AB - We have developed a significantly improved method for the electroporation of plasmid DNA into Staphylococcus aureus. The highest transformation efficiency achieved with this procedure was 4.0 x 10(8) transformants per microgram of plasmid pSK265 DNA. This represents a 530-fold improvement over the previously reported optimum efficiency of 7.5 x 10(5) transformants per microgram of plasmid DNA after electroporation of S. aureus cells [9]. Identical results were obtained when electrocompetent cells, which had been stored frozen at -80 degrees C, were used. The improved efficiency is due primarily to the use of a modified medium (designated as B2 medium) and secondarily to the use of 0.1-cm cuvettes. Several other plasmids (pI258, pMH109, and pSK270) were also electrotransformed into competent cells using our procedure, and for each plasmid, the transformation efficiency was significantly reduced compared to that observed when pSK265 DNA was used. With respect to plasmid pI258, the transformation efficiency was 3500 fold higher than that reported previously for transformation of this plasmid into S. aureus RN4220 [9]. The optimized electroporation procedure was less successful in transforming other staphylococci. Electrocompetent cells of S. aureus ATCC 29213 and S. epidermidis ATCC 12228 produced 5.5 x 10(5) and 5 x 10(3) transformants per microgram of pSK265 DNA, respectively. PMID- 1521763 TI - Transcription of glpT of Escherichia coli K12 is regulated by anaerobiosis and fnr. AB - The transcriptional expression of the sn-glycerol 3-phosphate transport gene, glpT, was studied with a glpT-lac fusion contained on a low-copy-number plasmid pFZY1. The fusion was isolated during a 'shot gun' cloning of promoters expressed under anaerobic growth conditions. It was shown that glpT was induced six-fold by anaerobiosis. Furthermore, aerobic expression of glpT was induced by the substrate glycerol 3-phosphate, while the anaerobic expression of glpT was decreased by nitrate, glucose and a fnr mutation. However, nitrate repression on glpT expression was relieved if the upstream region from -290 of the transcription site was removed. PMID- 1521762 TI - PCR amplification of streptococcal DNA using crude cell lysates. AB - Gram-positive organisms such as streptococci and enterococci are often difficult to lyse. Obtaining DNA for procedures such as PCR amplification usually requires a large scale isolation for each strain under investigation. We describe a simple procedure for small volumes of whole cells, involving pretreatment with detergent and proteinase that allows for efficient release of DNA for PCR amplification. This procedure is fast, reproducible, can be used with a large number of samples, and has been successfully applied to a variety of streptococcal and enterococcal strains. PMID- 1521764 TI - Sequential inactivation of ammonium and glucose transport in Saccharomyces cerevisiae during fermentation. AB - Ethanol at concentrations above 12% (v/v) in mineral medium with glucose and with ammonium as the only nitrogen source induced rapid inactivation of the ammonium transport system in the strain IGC 3507 of Saccharomyces cerevisiae terminating protein synthesis. Subsequently, when glucose was present, the glucose transport system was irreversibly inactivated. This two-step mechanism may play a decisive role when ethanol stops fermentation by S. cerevisiae, before all the fermentable sugar has been consumed. PMID- 1521765 TI - Cloning of a Clostridium thermocellum DNA fragment encoding polypeptides that bind the catalytic components of the cellulosome. AB - A test based on the binding of 125I-labelled endoglucanase CelD was used to clone a DNA region encoding at least two different polypeptides that interact with the conserved reiterated segment present in many catalytic components of the Clostridium thermocellum cellulosome. One of the polypeptides corresponds to the COOH-terminal region of the SL (or S1) component of the cellulosome (U.T. Gerngross and A.L. Demain, personal communication). It comprises repeated domains that are responsible for binding 125I-labelled CelD, and presumably represent anchoring sites for the various catalytic components of the cellulosome. The other polypeptide is encoded by a gene that has not yet been described. PMID- 1521766 TI - Differentiation of polyphosphate and poly-beta-hydroxybutyrate granules in an Acinetobacter sp. isolated from activated sludge. AB - Cells containing polyphosphate 71 micrograms P (mg protein)-1 and no poly-beta hydroxybutyrate showed metachromatic granules but no lipid granules; cells containing poly-beta-hydroxybutyrate (15% of dry weight) showed fluorescence lipid granules but no metachromatic granules; whereas cells containing both polyphosphate and poly-beta-hydroxybutyrate showed both types of granules. These observations, together with a critical review of the literature, show a clear distinction between metachromatic (or volutin) granules and lipid granules. PMID- 1521767 TI - Sequence and characterization of the gcpE gene of Escherichia coli. AB - In Escherichia coli, the gene gcpE encodes a protein of unknown function and lies immediately upstream of the hisS gene for histidyl-tRNA synthetase. The nucleic acid sequence of gcpE predicts an open reading frame for a protein of 40,681 Da. The probable transcription terminator of gcpE overlaps the hisS promoter. Haploid cells containing a disrupted gcpE could not be obtained, suggesting that the gcpE gene is essential. PMID- 1521768 TI - An extracellular enzyme from Fusarium solani f. sp. phaseoli which catalyses hydration of the isoflavonoid phytoalexin, phaseollidin. AB - Among the antimicrobial phytoalexins produced by Phaseolus vulgaris (French bean) are the prenylated isoflavonoids kievitone and phaseollidin. Two enzyme activities, kievitone hydratase and phaseollidin hydratase, occur in culture filtrates of the bean pathogen, Fusarium solani f. sp. phaseoli, and catalyse similar hydration reactions on the dimethylallyl moieties of the phytoalexins. The enzymes nearly co-purified during hydroxyapatite chromatography followed by preparative native gel electrophoresis. Eluates from successive slices taken from the native gel were assayed for both activities. Although they were not completely separated in the native gel, the activity profiles indicated that the two activities were distinct. The Km of phaseollidin hydratase for phaseollidin was approximately 7 microM. PMID- 1521769 TI - Evidence for the existence of a restriction-modification system common to several species of the family Vibrionaceae. AB - A broad-host-range vibriophage KVP40 originally isolated on Vibrio parahaemolyticus 1010 was restricted and modified by strains of at least five Vibrio and one Photobacterium species. 1010 was a non-restricting host. An anti restriction mutant KVP40 aar1 was isolated after propagating the phage on a restricting host, V. anguillarum VIB36. KVP40 aar1 grown on either 1010 or VIB36, as well as the parental phage grown on VIB36, showed much higher efficiencies of plating on all the restricting hosts as compared with the parental phage grown on 1010, indicating that these restricting hosts probably share a common restriction modification system active in vivo on KVP40. PMID- 1521770 TI - Modified peptidoglycan precursors produced by glycopeptide-resistant enterococci. AB - Cytoplasmic precursors of the peptidoglycan biosynthetic pathway were purified from vancomycin-treated, glycopeptide-sensitive and -resistant strains of Enterococcus faecium. Resistance was due to production of a modified precursor, UDP-MurNAc-L-Ala-D-Glu-L-Lys-D-Ala-D-lactate, where lactate was identified on the basis of mass of the precursor and on its ability to act as a substrate for D lactate dehydrogenase after release from the precursor. The presence of the D lactate residue instead of D-alanine in the terminal position would hinder formation of a vancomycin-precursor complex, without preventing incorporation of the precursor into mature peptidoglycan. PMID- 1521771 TI - Molecular monitoring of the transcriptional activation of the yeast Saccharomyces kluyveri mating pheromone signal transduction by using FUS1-lacZ fusion gene. AB - To analyse the molecular mechanism by which a mating pheromone signal is transmitted in Saccharomyces kluyveri, the S. cerevisiae FUS1-lacZ fusion gene was introduced into S. kluyveri cells and its transcriptional activation was investigated. The expression of FUS1-lacZ fusion product was cell-type specifically induced by pheromone treatment in S. kluyveri. The result suggests that S. kluyveri pheromone signal may be transduced by a mechanism similar to that in S. cerevisiae. This system may provide a model for analysing the molecular mechanism of the mating reaction in Saccharomyces kluyveri. PMID- 1521772 TI - The role of Eh, pH and iron in the bactericidal power of human plasma. AB - The bactericidal power of fresh human plasma against Klebsiella pneumoniae and Escherichia coli was extremely sensitive to changes in Eh and pH. At a high Eh (approx. +200 mV) the bacteria were destroyed, but rapid regrowth occurred when the Eh was lowered to approx. -400 mV. Abolition of the bactericidal effect was also produced by adding ferric iron at a high Eh (approx. +200 mV). Lowering the pH to 6.50 reduced or prevented the bactericidal effect. These results are probably related to the availability of iron for bacterial growth, and could be important for understanding the development of infection in injured or diseased tissue. PMID- 1521773 TI - pH track of expanding bacterial populations. AB - A method of pH distribution measurements in agar nutrient media containing expanding bacterial populations is described. It is based on measuring pH microsamples taken at different points of the media. The sample volume was 10 microliters. A pH sensitive field effect transistor was used as a measuring electrode. Acidification was found to occur in glucose media, while alkalization occurred in the media containing peptone. PMID- 1521774 TI - Comparative evaluation of the metabolic potentials of different strains of Peptostreptococcus productus: utilization and transformation of aromatic compounds. AB - Three strains of Peptostreptococcus productus were tested for growth at the expense of methoxylated aromatic compounds. Strain M8A-18 (human fecal isolate) was unable to utilize methoxylated aromatic compounds. While the type strain ATCC 27340 (human septicemia isolate) was capable of minimal growth with methoxylated aromatic compounds, ATCC 35244 (sewage sludge isolate) displayed significant growth on methoxylated aromatic compounds. Methoxylated phenols, benzoates, benzyl alcohol and phenylacrylates supported the growth of ATCC 35244 and were O demethylated to their respective hydroxylated derivatives. During O-methyl- or CO dependent growth, the double bond of the acrylate side chain of certain methoxylated and non-methoxylated phenylacrylates was reduced. Although other aromatic substituent groups (-COOH and -CH3) were transformed during CO-dependent growth, in short-term growth studies, the aromatic ring was not subject to reduction or degradation. Of the three strains tested, only strain M8A-18 failed to grow at the expense of carbon monoxide (CO). PMID- 1521775 TI - The location of the arginine-specific carboxypeptidase in the membrane of Mycoplasma salivarium and its physiological functions. AB - A non-penetrating probe, 2,4,6-trinitrobenzenesulfonate, inhibited the activity of the carboxypeptidase purified from the cell membranes of Mycoplasma salivarium and the same enzymatic activity of intact Mycoplasma cells as well. Growth of the organism in medium containing benzoylglycyl-L-arginine resulted in a higher pH and higher turbidity than growth in the same medium without this supplement. It was concluded that the enzyme existed in the outer surface of the membrane of the cells and probably functioned to supply the organism with arginine as an energy source. PMID- 1521776 TI - N-acetyl-isoleucine in Streptomyces avermitilis. PMID- 1521777 TI - Production of monovalent antisera by induction of immunological tolerance for capsular typing of Streptococcus pneumoniae. AB - Hyperimmune and high-titered polyclonal pneumococcal antisera, specific for cross reactive types within groups, were produced in adult rabbits. Purified capsular polysaccharide was injected intravenously into adult rabbits. One week later, these rabbits were given multiple intravenous injections of formalin-inactivated pneumococci of the cross-reactive type by an established method. Each of the resultant antisera were specific for the cross-reactive type indicating that the previous injection of the polysaccharide had induced epitope-specific tolerance. This method was successful for production of antisera against pneumococcal types 6A, 6B, 9N, 9V, 19F and 19A. Polyclonal rabbit pneumococcal antisera have some advantages over murine monoclonal antibodies for serologic studies and this method should be applicable for producing type-specific antibodies to cross reactive polysaccharides of clinical interest. Further, this method is simpler and generally produces higher titered monovalent (factor) reagents than absorbed antisera. PMID- 1521778 TI - Relationship between electroporation conditions, electropermeability and respiratory activity for Frankia strain ACN14a. AB - The use of electroporation for introducing macromolecules into intact cells of the actinomycete Frankia was investigated. Electropermeability was demonstrated by the uptake of dextran (70 kDa) molecules labeled with fluorescein isothiocyanate (FITC) inside Frankia cells. Upon pulsation with an exponentially decaying electric field, the cell membranes became permeable. Loading increased with initial pulsed electric field strength and capacitance. Increased loading efficiency was inversely related to INT (2-(p-iodophenyl-3-(p-nitrophenyl)-5- phenyltetrazolium chloride) reduction activity (respiring bacteria) of the cell population. The presence of CaCl2 in the electroporation and resealing buffer raised INT-reduction activity but K2SO4 decreased this activity. Resealing of electropores was confirmed by a decreasing FITC-dextran loading through the recovery period. The use of FITC-dextran molecules and INT-reduction assay are two new approaches for the study of permeabilization and cellular activity of electroporated bacteria. PMID- 1521779 TI - Genetic variation in two bone-related proteins: is there an association with bone mineral density or skeletal size in postmenopausal women? AB - In an effort to determine if structural variation in proteins important in bone metabolism might influence bone mineral density (BMD) and thus be a determinant of susceptibility to osteoporosis in older women, the authors typed a group of 258 non-Black women (age 65-90) participating in the Study of Osteoporotic Fractures (SOF) for two polymorphic bone-related proteins, group specific component (Gc), also known as vitamin D-binding protein, and alpha 2HS glycoprotein (AHSG). These two proteins exhibit common structural variation in populations that can be detected by isoelectric focusing/immunoblotting of serum. An important function of Gc is the binding, solubilization, and transport of vitamin D sterols in the bloodstream while AHSG is a glycoprotein constituent of calcified cortical bone matrix. There are six common phenotypes of Gc and four of AHSG. Using Gc or AHSG phenotypes as categorical variables, statistical analyses were done to determine if bone mineral density of the proximal or distal radius or calcaneus differed by phenotype. Neither Gc nor AHSG phenotype demonstrated a statistically significant relationship with BMD at any site. Adjustments for age and degree of obesity did not substantively affect these results. Subsequent analyses to determine if phenotype of either of these proteins was associated with variables related to skeletal size showed an association of AHSG with height (P less than .02). This may indicate that AHSG phenotype is related to postmenopausal loss of height, or it may be a chance statistical finding. PMID- 1521780 TI - Familial analysis of eosinophilia caused by helminthic parasites. AB - A highly significant familial aggregation of eosinophil levels (X2(3) = 38.00) was detected in a sample from three Brazilian populations with a high incidence of helminthic parasitism. The data were unable to resolve genetic or common environment causation due to the lack of environmental concomitant variables. Results of path analysis indicate that the familial cause accounts for about 58% of the total variability of eosinophil levels among parasite-infected individuals. PMID- 1521781 TI - Do bilineal pedigrees represent a problem for linkage analysis? Basic principles and simulation results for single-gene diseases with no heterogeneity. AB - Some investigators have expressed concern--especially for psychiatric disorders- that bilineal pedigrees should not be included in linkage studies. This study compares the "informativeness" of bilineal and unilineal families for a homogeneous single-gene disorder. Three approaches were used: (1) simulation studies of three-generation pedigrees, (2) calculation of expected lod scores (ELODs) in nuclear families, and (3) calculation of Fisher's information number I(theta) in nuclear families. The simulation studies in (1) permitted a realistic comparison between bilineal datasets and purely unilineal ones. The calculations in nuclear families in (2) and (3) then made it possible to analyze the sources of information loss in bilineal families. Overall, in datasets of five three generation pedigrees each, the drop in mean maximum lod score was approximately 50% from purely unilineal datasets to extremely bilineal ones. In less-extreme bilineal datasets, which are closer to most real data than the extremely bilineal ones, the drops in lod score were very small--less than 10% in some, and practically zero in others. The details will vary, depending on size and structure of the pedigree, genetic model, true value of the recombination fraction, and informativeness of the marker. However, these results imply that the information loss due to bilineality is not necessarily very great. The nuclear-family calculations showed that for phase-known matings there is relatively little information loss in bilineal families, but for phase-unknown matings there the loss is much greater. In conclusion, for single-gene disorders with no genetic heterogeneity, whereas bilineal families can be less informative than comparable unilineal families, they are not so much less informative that they should automatically be discarded from linkage datasets. The implications of bilineal pedigrees for linkage studies of heterogeneous disorders are also discussed. PMID- 1521782 TI - Detection of genetic heterogeneity for complex quantitative phenotypes. AB - Statistically characterizing factors responsible for quantitative phenotype expression (e.g., polygenes, major genes, shared household factors, etc.) through model selection strategies is a difficult task. A great deal of effort has been expended on refining mathematical and computational aspects of various segregation models used to characterize unique expressions of quantitative phenotypes in an effort to make these models easier to implement and evaluate for a given set of data. In this paper a slightly different angle is emphasized: namely, the explicit modeling of the potentially numerous heterogeneous genetic and environmental processes (i.e., segregation patterns, household aggregations, etiologic processes, etc.) that could contribute to the overall variation of a quantitative trait. As such, this paper describes tools for detecting quantitative trait heterogeneity that are meant to answer such questions as "are there pedigrees among a great many that show a pattern consistent with a possibly very specific single locus segregation pattern while the rest show compatibility with a polygenic or purely environmental pattern?" Methods for determining the significance of such heterogeneity are also discussed, as are the results of numerous examples and simulation studies carried out in an effort to validate and further elaborate aspects of the proposed techniques. PMID- 1521783 TI - Case definitions in primary care. The need for clinical epidemiology. PMID- 1521784 TI - SPECT imaging in psychiatry. A review. AB - In the last two decades, brain imaging has become an integral part of clinical and research psychiatry. Single photon computed emission tomography (SPECT) is rapidly gaining acceptance as one of the major imaging techniques available, along with computed tomography (CT), magnetic resonance imaging (MRI), and positron emission tomography (PET). Each of these techniques has its assets and drawbacks. This review concerns SPECT, a highly prevalent imaging technique whose potential value in brain imaging has not been appreciated until recently. Its purpose is to expose practicing clinicians and research psychiatrists alike to the attributes of this instrument, which is available in most nuclear medicine departments today. An effort is made to provide a comprehensive account of this technique, including a brief summary of the basic principles, the various methods of its application, and recent findings in most psychiatric disorders. Analogies to its "aristocratic cousin," PET, are presented to emphasize similarities and differences. Finally, directions for future development and implementation of SPECT are suggested. PMID- 1521785 TI - Prevalence of psychiatric disorders in three primary-care clinics in Beersheba, Israel. Concurrent assessment by the General Health Questionnaire, General Practitioners, and Research Diagnostic Criteria. AB - The General Health Questionnaire (GHQ) had identified fully 69% of 776 respondents who attended 12 primary-care clinics as "probable cases" of psychiatric disorders, whereas the general practitioners (GPs) involved had thought only 31% had psychological problems. To investigate more accurately the prevalence of psychiatric disorders we examined 112 of the original sample with the Schedule for Affective Disorders and Schizophrenia, Life-time version and found only 15% to have had a Research Diagnostic Criteria disorder at the time of the initial study. Raising the GHQ threshold to 15/16 improved specificity and positive predictive value, and improved GPs' case-finding modestly. These respondents either suffered from high rates of subclinical distress or readily report subjective distress in the clinic, or both. PMID- 1521786 TI - Crying following stroke. A report on 30 cases. AB - Following stroke, many patients experience a heightened tendency to cry. The aim of the present study was to provide a detailed description of this behavior and its accompaniments. Thirty stroke patients who had cried in the previous month were studied using a detailed structured clinical interview. There was a wide range of frequency of crying. The components of crying combine in a more complex and varied way than commonly held stereotyped views suggest. No distinct subtypes were identified. Further research is required to determine the relationship between emotionalism and the frequency and severity of symptoms of depression. PMID- 1521787 TI - The comorbidity of DSM-III-R personality disorders in somatization disorder. AB - In order to understand psychiatric factors that complicate the medical management of somatizing patients, 94 subjects with known somatization disorder (SD) were evaluated for 13 personality disorders with the Structured Clinical Interview for DSM-III-R Personality Disorders. Referred from multiple primary care settings, the patient sample was predominantly female (85%), married (67%), high school graduates (64%), and had a mean age of 43. Structured interviews documented that 23.4% of SD patients had one personality disorder, and 37.2% had two or more disorders. The four most frequently identified personality disorders were avoidance 26.7%, paranoia 21.3%, self-defeating 19.1%, and obsessive-compulsive 17.1%. Interestingly histrionic personality disorder was identified in only 12.8% of the sample and antisocial personality disorder in 7.4%. In making the diagnosis of SD, health care providers need to avoid the common clinical impression that histrionic behavior often accompanies the disorder. Further research with SD patients is needed to examine the relationship of co-occurring personality disorders to symptom recurrence, health care utilization, and readiness for psychiatric referral. PMID- 1521788 TI - Resuscitation. Patient and staff attitudes in the context of cancer. AB - One hundred oncology and hematology cancer patients from a major teaching hospital and their treating doctors were studied regarding their attitudes toward cardiopulmonary resuscitation (CPR). A descriptive approach was used, incorporating semistructured interviews of patients and medical staff and established questionnaire measures, examining knowledge of and attitudes toward disease and treatment, and projected attitude toward CPR and current psychological functioning. One-third of the patient sample anticipated a time when they would not consent to cardiopulmonary resuscitation. This was significantly associated with good disease prognosis. Patients with a psychiatric past history were also overrespresented. It appears that patient attitude to treatment withdrawal and refusal of CPR is related to disease progression and likely to change over time. This supports a dynamic and evolving model of advance directives rather than any fixed decree. Medical staff reported that they planned to provide half the sample with intensive medical treatment (including Intensive Care support in the event of their cardiac arrest), and 32% were designated for ward-based resuscitation only. Eighteen percent would not be resuscitated. These patients were older, had more treatment side effects, and a poorer quality of life. Those patients with either a psychiatric past history or higher ratings of depressive affect were also overincluded in the doctors' "Do-Not-Resuscitate" (DNR) group. These results suggest that there are other qualitative factors (e.g., current psychological functioning and past psychiatric history) that contribute to DNR decisions beyond the usual disease-based criteria seen in formal DNR protocols. PMID- 1521789 TI - Thyroid screening tests in psychiatric inpatients. AB - This study reports on a retrospective evaluation of the current practice of screening for thyroid dysfunction in an adult psychiatric inpatient program. Sixty-four percent of 342 admissions were tested during their hospital stay. Although 13.7% of tests yielded abnormal values on one or more of the thyroid indices, only 0.9% resulted in a diagnosis of hypothyroidism. None of the other abnormal test results led to any specific action being taken. The present pattern of use of thyroid function screening as observed in this study does not appear optimal. Issues in the selection of thyroid screening tests, and the value of the results obtained are discussed. PMID- 1521790 TI - Use of increased anesthetic dose prior to electroconvulsive therapy to prevent postictal excitement. AB - The authors report on three patients who developed severe postictal excitement at several consecutive electroconvulsive therapy (ECT) treatments. In all three cases, an increase in the anesthetic (or equivalent medication) dosage prior to ECT prevented the emergence of postictal excitement at subsequent treatments. This strategy, among others, should be considered in the management of patients who repeatedly manifest this phenomenon during a course of ECT. PMID- 1521791 TI - Dissociative experiences among psychiatric inpatients. AB - The Dissociative Experiences Scale was administered to 299 inpatients on an acute care general adult psychiatric ward over a 2-year period. The average score was 14.6, which is significantly higher than the mean for the general population. About one in six inpatients reported very high scores above 50 on the seven most common items in the scale, indicating a high level of dissociative psychopathology. Based on the responses to four items which form a scale factor called Activities of Dissociated States, an estimate is made that 6%-8% of general adult inpatients may have multiple personality disorder. Dissociative psychopathology is common on inpatient units. PMID- 1521792 TI - Factitious disorder resulting in bilateral mastectomies. PMID- 1521793 TI - Anorexia nervosa/bulimia and central pontine myelinolysis. PMID- 1521794 TI - [Analysis of the origin of the Vietnam dairy cow breed using the results of marker character study]. AB - The phylogenesis analysis of Vietnam milk cows breed was performed using eleven different mathematical methods. 14 to 144 markers were used in this analysis, whose synthesis is controlled by eleven genetical systems of blood groups and six polymorphic systems of proteins. It has been demonstrated that the accuracy of the phylogenesis analysis depends on the quality of the markers applied and on the methods used. It was established that the way of breed formation was reflected in the dendrogram composed by the matrix based on the formula of Eisner and Meshcheryakova (1978). The properties of other methods in use are discussed. PMID- 1521795 TI - [Genetic analysis of some behavioral and physiologic characters in hybrids between hypertensive and normotensive rats. Analysis of the nature of the inheritance]. AB - As a result of crosses between the SHR rats (spontaneously hypertensive strain) and WKY rats (normotensive strain), the F1 and F2 hybrids and the B1 and B2 backcrosses were obtained. Analysis of genetic control nature in these generations revealed that the WKY genes responsible for the level of arterial pressure, sensitivity to the electric current stimulation and salt (sodium and potassium) appetite characteristics were dominant. The heterosis effect was found for the body mass. Analysis of dynamics of different types of exploratory activity (in a shuttle box, in "horizontal plane", in an open field) demonstrated specificity of their genetic formulae and peculiarities of changes in their genetic control during the test. PMID- 1521796 TI - [Transcription activity of ribosomal genes in the pre- and postnatal periods of human development]. AB - Transcriptional activity of silver-stained nucleolar-organizing region (NOR) of human chromosomes was studied in 50 medical abortuses at 6-12 weeks of gestation and 125 healthy individuals from 20 to 85-years-old. Transcriptional activity of rRNA genes was higher at the prenatal period of ontogenesis than at the postnatal period. Decline in total activity of ribosomal genes in both sexes was shown. Linear regression coefficients of the NOR activity in dependence of age satisfactorily predict the level of total NOR activity at the prenatal period of human development. PMID- 1521797 TI - [Ecologic ultraviolet--a real mutagenic factor for vegetative cells of Bacillus subtilis]. AB - The frequency of leu----Leu+ reversions represented mainly by suppressor mutations is increased in Bacillus subtilis uvr+ and uvr-1 cells after exposure to natural sunlight. Dependence of mutation yield on the time of exposure is linear (one hit kinetics) in case of the uvr-1 strain. In the uvr+ cells the yield of mutations is also linear, but only at short times of exposure, the curve bending and levelling off the plateau after 10-min cell illumination. It has been established in the experiments with optical filters that the mutagenic effect is related to wavelengths which correspond to the UVB zone of ecological UV. The mutagenesis caused by sunlight can be modified (weakened) by some post irradiation treatments of bacteria, which also led to a decrease of mutations frequencies in B. subtilis uvr+ and uvr-1 cells after exposure to 254-nm UV. The data indicate that: 1) mutagenic influence of sunlight can be overcome only by the joint action of activities of the two cellular repair systems- photoreactivation and excision repair, 2) the real mutagenic effect of sunlight on such a non-photoreactivating organism as B. subtilis would not be enhanced with the increase of the UVB flow in sunlight spectrum. PMID- 1521798 TI - [Integration of the plasmid-cloned lysA gene of Bacillus subtilis into the chromosome of this microorganism]. AB - Integration of the Bacillus subtilis lysA gene cloned on pLP1 plasmid, into the 250 degrees region of the chromosome of this microorganism was performed. Significant differences in the level and character of their expression were shown between lysA gene integrated into the chromosome and plasmid-borne genes. It is suggested that the expression of the lysA gene could be under control of a certain cis-acting factor which is able to promote transcription of the lysA gene and mediate gene specific regulation. PMID- 1521799 TI - [The plasmid pEJ6.6 carrying the activated c-Ha-ras-1 oncogene increases the mutation frequency in Chinese hamster cells]. AB - The induction of gene mutations and chromosome aberrations by the plasmid pEJ6.6 carrying the activated c-Ha-ras-1 oncogene from human bladder carcinoma was studied in cultured Chinese hamster cells. Both an increase in the frequency of gene mutations to 6-mercaptopurine resistance and of chromosome aberrations was observed after pEJ6.6 treatment as compared to control series (pBR322). Thus the results of experiments carried out show that the pEJ6.6 plasmid possesses a mutagenic activity. PMID- 1521800 TI - The foraging locus: behavioral tests for normal muscle movement in rover and sitter Drosophila melanogaster larvae. AB - We used Drosophila melanogaster larvae with different alleles at the foraging (for) locus in a variety of behavioral tests to evaluate normal muscle usage of rover and sitter phenotypes. The results show that sitter and lethal sitter alleles of for do not affect larval behavior through a mutation which affects larval muscle usage. In general the behavior of rovers and sitters differed on food but not on non-nutritive substrates. Rovers and sitters moved equally well on non-nutritive substrates, and measures such as the time to roll over and length of forward stride showed no significant strain differences. Larvae with different alleles at for did not differ in body length. Rovers took more strides, not longer ones, than sitters while on foraging substrates. We conclude that differences in larval locomotion during foraging found in larvae with different alleles at for can not be explained on the basis of muscle usage alone. It is more likely that for affects larval ability to perceive or respond to the foraging environment. PMID- 1521801 TI - Karyotypic comparison among Cebuella pygmaea, Callithrix jacchus and C. emiliae (Callitrichidae, Primates) and its taxonomic implications. AB - The karyotype of Cebuella pygmaea (2n = 44) obtained by G-, C-banding, and NOR staining is described. This species presents a heteromorphic C band in the intersticial region of the short arm of chromosome 2. The data obtained were compared with those previously described for the karyotypes of Callithrix jacchus and Callithrix emiliae. The three species differ in the amount and distribution of non-centromeric constitutive heterochromatin. The importance of the variation in constitutive heterochromatin for the phylogeny of the group is discussed. Comparison of the karyotypes in terms of G-banding patterns showed that C. pygmaea and C. emiliae differ from C. jacchus by a Robertsonian translocation and a paracentric inversion, whereas C. pygmaea and C. emiliae differ from each other by a reciprocal translocation between an acrocentric autosome and the short arm of the submetacentric chromosomes that distinguishes their karyotypes from that of C. jacchus. The possible evolutionary paths followed by the karyotypes of the three species are discussed. PMID- 1521802 TI - Topical indomethacin in the treatment of chronic cystoid macular edema. AB - Eighty percent of 30 eyes with chronic cystoid macular edema (CME) after cataract extraction achieved improved visual acuity of three or more lines when treated with 1% indomethacin eye drops. Of these patients 53% demonstrated an "on/off" phenomenon induced by the initiation and cessation of treatment documented by visual acuity measurements and fluorescein angiography. This "on/off" phenomenon suggests that there is a direct relationship between the use of 1% indomethacin eye drops and the resolution of chronic CME after cataract extraction. Previous studies on the treatment of CME with indomethacin have not addressed the use of indomethacin eye drops for chronic CME. PMID- 1521803 TI - Intraocular pressure determination in infants with severe retinopathy of prematurity. AB - We determined intraocular pressure (IOP) in 55 premature infants (122 determinations) with stage V retinopathy of prematurity (ROP) by applanation and indentation tonometry corrected for scleral rigidity and found a modest correlation of r = 0.52 between readings. Chronologic age and the scleral rigidity coefficient were the most significant factors affecting the closeness in readings. Our findings suggest that the applanation method of obtaining IOP values is preferable in infants with ROP because this method is less affected by technical error and the variable nature of premature infant sclera. Frequent examination may be necessary to detect an early IOP increase, especially in infants who have had successful retinal reattachment through vitreoretinal techniques. PMID- 1521804 TI - Chlamydia keratoconjunctivitis determination of Chlamydia trachomatis specific secretory immunoglobulin A in tears by enzyme immunoassay. AB - Determination of Chlamydia trachomatis specific antibodies in serum and tears, isolation of C. trachomatis in cell culture and C. trachomatis antigen detection by direct immunofluorescence test were evaluated for the laboratory diagnosis of Chlamydia trachomatis infection in 30 patients with chronic conjunctivitis. C. trachomatis specific secretory immunoglobulin A (s-IgA) was detected in the tears of all 8 patients with a positive result in culture and the direct immunofluorescence test. In 4 additional patients, the s-IgA assay of tears was also positive. A presumptive clinical diagnosis of Chlamydia conjunctivitis was correlated with the presence of s-IgA in tears. S-IgA was not detected in the serum of any of the patients, indicating that s-IgA is locally produced and not transudated from the serum. For the diagnosis of chronic Chlamydia conjunctivitis, we recommend the determination of s-IgA in tears in addition to a test for Chlamydia detection. PMID- 1521805 TI - Apparent cleavage of the retinal nerve fiber layer in asymptomatic eyes with high myopia. AB - The appearance of the retinal nerve fiber layer was studied in one eye of 203 normal Asians (59 with high myopia greater than or equal to -5 D, and 144 with emmetropia or hyperopia). "Cleavage" of the retinal nerve fiber layer was observed in 3 of these 59 highly myopic eyes, but there was no significant damage to either the retinal pigment epithelium or the choroid. In contrast, no cleavage was observed in the other 144 emmetropic or hyperopic eyes. High myopia (P = 0.0237, Fisher's exact test) was a significant risk factor for "cleavage" development in the retinal nerve fiber layer. The occurrence of a defect (nerve fiber loss) in the retinal nerve fiber layer in severe myopia (5/59, 8%) was also greater than that in either emmetropia or hyperopia (2/144, 1%; P = 0.0229). These results indicate that subtle changes can occur in the appearance of the retinal nerve fiber layer of the eye in some patients with asymptomatic myopia. PMID- 1521806 TI - Extracellular matrix changes of the optic nerve lamina cribrosa in monkey eyes with experimentally chronic glaucoma. AB - Using light microscopic immunohistochemistry, we studied the immunolocalization and immunoreactivity of the extracellular matrix, including collagen types III, IV, VI, laminin, and alpha elastin in the lamina cribrosa of monkey eyes with normal and experimentally chronic glaucoma. Our results showed: (1) abnormal linearlike immunodeposits of both collagen type IV and laminin in the margin of the lamina cribrosa with significant density in the glaucomatous eyes; (2) the immunoreactivity of collagen type III resembled that of the normal eye, but was slightly stronger at the laminar surface; (3) findings with collagen type VI resembled those of type III with an enhanced linearlike staining surrounding the nerve-fiber bundles. Furthermore, staining of alpha elastin demonstrated dramatic changes in both reactivity and localization. The lamina cribrosa of glaucomatous eyes showed a markedly reduced immunoreactivity as well as an irregular, interrupted pattern. These observations suggest that the changes might be a secondary to the long-standing elevation of intraocular pressure. The alteration of these macromolecules may modify the course of glaucomatous optic damage. PMID- 1521807 TI - Immunohistochemical detection of extravasated fibrinogen (fibrin) in human diabetic retina. AB - In diabetic retinopathy, breakdown of the blood-retinal barrier is an early functional disorder that can cause retinal edema, which in turn results in visual disturbance. Hard exudates, composed mainly of lipid and proteinaceous material, are one sign of chronic retinal edema caused by long-standing leakage from the vessels due to breakdown of the blood-retinal barrier. Utilizing diabetic retinas in which hard exudates were present, we performed immunohistochemical staining for fibrinogen. Because fibrinogen is a serum protein, its extravascular localization implies the existence of blood-retinal barrier breakdown. Our studies showed that the extravasated fibrinogen from blood-retinal barrier breakdown accumulated in the hard exudates and in areas of hemorrhage found primarily in the outer plexiform layer and was then phagocytosed by macrophages. PMID- 1521808 TI - Digital image analysis of optic nerve head pallor as a diagnostic test for early glaucoma. AB - We developed a computer-based technique to quantify optic nerve head pallor from videographically acquired digitized optic nerve images and tested the ability of pallor measurements to discriminate between normal eyes and eyes with early glaucoma. Corresponding pixel values from images obtained under 540 nm (green) and 640 nm (red) light with a videographic fundus camera were used to quantify optic nerve head pallor. A pallor density histogram was calculated for each eye, and contained values between 0 (red) to 1 (white). A measure of the distribution width of the histogram provided pallor measurements standardized to the measurements of the large veins of the disc. A database of one eye each of 44 normal controls and 70 patients with early open angle glaucoma was used to test the measurements for diagnostic sensitivity and specificity. These standardized pallor measurements did not perform better than absolute pallor measurements to discriminate between normal and glaucomatous eyes. The sensitivity and specificity of standardized pallor measurements (49% and 57%, respectively, for this database) were not as good as those for stereoscopic measurements of disc rim area in the same database (70% and 73%). Pallor measurements of this type do not appear to be sensitive or specific indicators of early glaucoma. PMID- 1521809 TI - Alterations of saccadic eye movements in myotonic dystrophy. AB - Saccadic eye movements were examined by means of infrared reflection oculography in 8 patients having myotonic dystrophy and in 65 control subjects. In 7 patients typical alterations of the saccades could be observed. In comparison with the normal controls the saccades were significantly hypometric, of longer duration, of lower peak velocity, and showed a typical pattern of velocity and acceleration. PMID- 1521810 TI - Retinal vessel autoregulation in sickle cell patients. AB - We tested retinal vessel autoregulation in 16 sickle cell patients and 6 controls by computer-assisted measurements of constriction of the superior and inferior temporal veins and arteries after pure oxygen breathing. Compared to the controls and corrected for age, we found a decrease of vasoconstriction in three of the four vessels measured in the sickle cell group, which was statistically significant only for the superior temporal artery (P 0.009). The number of patients was too small to allow a separate analysis of possible contributory factors within the sickle cell group, such as sickle cell hemoglobin subtype and extent of retinal ischemia. Our findings indicate a factor not yet well known in the pathophysiology of sickle cell disease: an abnormality of local microvascular control. PMID- 1521811 TI - A comparative study of optic nerve head in low- and high-tension glaucomas. AB - The disc and rim areas in 15 eyes from 15 selected low-tension glaucoma (LTG) patients were compared with those in 15 eyes from 15 selected high-tension glaucoma (HTG) patients. In all patients, visual field defects (VFD) were at an early stage (mean deviation greater than -5 dB, program 30-2 of Humphrey Visual Field Analyzer, STATPAC) and were confined to either the upper or lower hemifield. There were no significant differences in the degree of VFD between LTG and HTG, and the peak intraocular pressure averaged 18.9 and 29.2 mmHg for LTG and HTG eyes, respectively. The disc and rim areas were determined from stereoscopic disc photographs using the method of Littman. The half rim area corresponding to the upper or lower hemifield without VFD was significantly smaller for LTG than HTG (LTG 0.26 +/- 0.08 mm2, HTG 0.31 +/- 0.08 mm2, mean +/- SD, n = 15, P less than 0.005). The rim area corresponding to the upper or lower hemifield with VFD was also significantly smaller for LTG than HTG (LTG 0.19 +/- 0.08 mm2, HTG 0.24 +/- 0.08 mm2, P less than 0.01). On the other hand, there was no significant difference in the disc area between LTG and HTG (LTG 1.96 +/- 0.57 mm2, HTG 2.03 +/- 0.45 mm2, P greater than 0.4). It was suggested that the differences in rim area were already present prior to the manifestation of the VFD. PMID- 1521812 TI - Effect of dexamethasone 0.1% and prednisolone acetate 1.0% eye drops on the blood aqueous barrier after cataract surgery: a controlled randomized fluorophotometric study. AB - Using non-invasive anterior chamber fluorophotometry, we performed a double blind, randomized clinical trial on the effects of dexamethasone 0.1% and prednisolone acetate 1.0% eye drops on the blood-aqueous barrier after phacoemulsification and posterior chamber lens implantation. Twenty patients received one of the preparations topically to the surgically treated eye 5 times daily for a period of 5 days, beginning the day after surgery. Patients chosen for the study had no history of eye disease other than senile cataract nor of systemic diseases influencing the eyes. No other steroids or non-steroidal anti inflammatory drugs were given before or during the investigation. The fluorometric data measured 5 days after surgery show a lower mean concentration of fluorescein in the dexamethasone alcohol 0.1% treated group compared with the prednisolone acetate 1.0% treated group. The difference is statistically not significant. The clinical assessment of postoperative ocular inflammation did correlate with the fluorophotometric measurements. The results of the study indicate that although dexamethasone is the more potent anti-inflammatory agent, with a better binding affinity to glucocorticoid receptors, we are--with the number of cases measured--unable to demonstrate any difference in the efficacy in protecting the blood-aqueous barrier after cataract extraction and posterior chamber lens implantation to prednisolone acetate. PMID- 1521813 TI - Bullous retinal detachment and multiple retinal pigment epithelial detachments in patients receiving hemodialysis. AB - Two patients receiving hemodialysis for chronic renal failure developed bilateral bullous retinal detachment associated with multiple underlying serous detachments of the pigment epithelium. Many of the detachments of the pigment epithelium were surrounded by subretinal whitish exudate that was probably fibrinous in type. There was fluorescein angiographic evidence of dehiscence of the pigment epithelium at the margin of some of the pigment epithelial detachments. Failure to recognize the nature of the retinal detachment in one patient resulted in an unsuccessful scleral buckling procedure. PMID- 1521814 TI - Prognostic value of new retinal tears associated with the development of postoperative proliferative vitreoretinopathy. AB - We prospectively evaluated for the presence of new retinal tears 60 eyes of 60 patients who developed recurrent retinal detachment complicated by proliferative vitreoretinopathy (PVR) after surgery for primary rhegmatogenous retinal detachment. New retinal tears associated with the development or recurrence of postoperative PVR were disclosed in 27 eyes (45%). New tears were categorized into two distinct groups: (1) peripheral new tears and (2) posterior new tears. Peripheral new tears were disclosed in 11 eyes. They were invariably located at the posterior edge of the vitreous base and showed a prevalence in the inferior quadrants. The prognosis for permanent retinal reattachment after reoperation was not influenced by the presence of peripheral new tears. Posterior new tears were disclosed in 19 eyes. They were located in the mid-periphery or close to the posterior pole. They were more frequent in grade D PVR (57.7%) compared with grade C PVR (11.7%) (P less than 0.01). Posterior new tears were associated with a poor prognosis. In grade D PVR the anatomic success rate following repeated surgery was only 13.3% (2/15 eyes), whereas all eyes with grade D PVR and no posterior new tears were successfully reattached (P less than 0.001). Failures to reattach the retina were related to recurrent PVR. It is concluded that the development of posterior new tears in postoperative PVR reflects a severe and active PVR process. PMID- 1521816 TI - The ultrastructure of transplanted rabbit retinal epithelium. AB - Retinal epithelial cells from pigmented rabbits have been cultured and radiolabelled during division with 3H-thymidine and transplanted to the subretinal space of albino rabbits using a pars plana transvitreal approach. The host rabbits were maintained on cyclosporine immunosuppression after transplantation surgery. The transplant cells survive and maintain a morphologically normal appearance for at least 5 months. The pigmented epithelial cells retain their pigmentation and become integrated with the host retinal epithelium forming junctional complexes with both the host and other transplant cells. The transplant cells contact host photoreceptors with their apical processes and phagocytize outer segments. There appears to be no significant cell division among the transplant cells. PMID- 1521815 TI - Cellular response to intravitreal injection of endotoxin and xanthine oxidase in rabbits. AB - In the present study, the ocular inflammatory response to intravitreally injected endotoxin and xanthine oxidase was studied and the cellular response of the anterior and posterior segments was contrasted. There was a clear dose response relationship to both compounds in aqueous humor protein concentration and aqueous and vitreous humor white cell number. Xanthine oxidase and low doses of endotoxin (0.25 and 1.0 ng) produce a mainly mononuclear response in the anterior segment. Higher doses of endotoxin (10 and 100 ng) produced a predominantly neutrophilic response. Cellular infiltration into the posterior segment differed qualitatively and quantitatively from the anterior segment in response to the same stimuli. Myeloperoxidase (MPO) activity (a marker for neutrophils) of the iris-ciliary body was increased only in those eyes with a large neutrophilic response and thus is not recommended for use as a definitive index of the ocular inflammatory response, but may be a useful adjunct for such studies. PMID- 1521817 TI - Developmental study of chondroitin-6-sulphate in normal and dystrophic rat retina. AB - The RCS rat is a widely studied model of human retinal dystrophies including retinitis pigmentosa. Chondroitin-6-sulphate (C6S) in the interphotoreceptor matrix was localised immunocytochemically in both the normal congenic and dystrophic strains of the RCS rat up to 65 days postnatally. From postnatal days 5 to 15 the distribution of C6S in both strains was similar, being localised in the interstices of developing inner and outer segments and adjacent to the RPE surface. In the normal rats, the distribution of C6S did not change with age. In the RCS rats, however, at postnatal days 20 to 35 staining was observed as a dense band at the junction of inner and outer segments and no staining was observed adjacent to the surface of the RPE. At postnatal day 45 onwards there was a decrease and a complete absence of C6S staining in these rats. This change in the pattern of staining correlated with the morphological observation of the progressive degeneration of photoreceptor cells suggesting that C6S may be important in photoreceptor degeneration in the RCS rat. PMID- 1521819 TI - Vitreous, retinal and subretinal hemorrhages associated with von Willebrand's syndrome. AB - Two patients with von Willebrand's syndrome had intraocular hemorrhages without trauma or neovascularization. A 13-year-old Japanese girl complained of sudden spotted vision in her left eye. Vitreous, peripapillary retinal, and subretinal hemorrhages were seen by ophthalmoscopy in the affected eye. In addition, a 19 year-old Japanese man had repeated vitreous hemorrhage and epistaxis. Also noted was gyrate atrophy of the choroid and retina. Analysis of the coagulation fibrinolysis system revealed decreased activities of Factor VIII and von Willebrand's factor in both patients. The amount of von Willebrand's factor antigen also was decreased. These results suggested that the patients had von Willebrand's syndrome. The bleeding tendency in the disorder appeared to be responsible for the pathogenesis of the intraocular hemorrhages seen in these patients. PMID- 1521818 TI - Toxicity of 1-(beta-D-arabinofuranosyl)cytosine after intravitreal injection in the rabbit eye. AB - The retinal toxicity of intravitreally injected 1-(beta-D arabinofuranosyl)cytosine (cytarabine) was examined in 7 chinchilla rabbits to determine if cytarabine can be used as local therapy for vitreoretinal non Hodgkin's lymphoma. Fractionated dose of 600 micrograms, 1500 micrograms, and 2700 micrograms cytarabine in stabilized saline were given intravitreally in one eye (2 x 300 micrograms, 5 x 300 micrograms, and 3 x 900 micrograms, respectively, with an interval time of 24 h) and stabilized saline in the other eye as control. Toxic effects were evaluated with biomicroscopy, direct ophthalmoscopy, fluorophotometry, electroretinography, light, and electron microscopy. Toxic effects were found with the 1500 micrograms and 2700 micrograms doses only. They consisted of a temporary impairment of the blood retina barrier function for fluorescein as measured by fluorophotometry and an irreversible change of the b-wave in the electroretinograms. No histopathologic changes were seen under the light microscope. Electron microscopic examination showed aberrations in the synaptic pedicles of the photoreceptor cells at a dose of 1500 micrograms cytarabine. The results suggest that the cytarabine dose that is expected to be therapeutic for vitreoretinal non-Hodgkin's lymphoma (about 90 micrograms given in three doses of 30 micrograms) is non-toxic for ocular structures. PMID- 1521820 TI - Fundus flavimaculatus and subretinal neovascularization. PMID- 1521821 TI - The Gerontological Society of America, 45th annual scientific meeting. Health Challenges of our Aging Society. Washington, D.C., November 18-22, 1992. Abstracts. PMID- 1521822 TI - ISFRR VI biennial meeting. Free radicals: from basic science to medicine. Torino, Italy, June 16-20, 1992. Abstracts. PMID- 1521823 TI - Low-dose danazol for vascular access and dialyzer thrombosis in hemodialysis patients. AB - Four hemodialysis patients (1 male and 3 females, aged 29-40 years) with unusual recurrent vascular access or dialyzer thrombosis were studied to find out whether a hypercoagulable state exists. Measurements of euglobulin clot lysis time (ELT), fibrinogen, antithrombin III (AT III), protein C (PC), protein S (PS), tissue plasminogen activator (tPA), and plasminogen activator inhibitor (PAI) were done. Results indicated that all patients had prolonged ELT, low tPA, elevated PAI, normal AT III, and PS. Three patients had elevated fibrinogen level and two had low PC. Danazol 200 mg orally once a day effectively prevented any further thrombosis. In 4 weeks' time, all the abnormal coagulation studies normalized in addition to elevation of AT III, PC and PS. Only 1 female patient had a prolonged menstrual period, which was reversed by lowering the daily dose of danazol to 100 mg. No other side effects were encountered. These data indicate that hypofibrinolysis may play a major role in vascular access or dialyzer thrombosis and that low-dose danazol may provide an effective prophylaxis and treatment. Larger controlled studies are needed to confirm these findings. PMID- 1521824 TI - Factor VIII concentrates in HIV-1-positive hemophiliacs--is pure better? AB - 39 human immunodeficiency-virus-1 (HIV-1)-positive hemophiliacs who had been regularly treated with non-virus-inactivated intermediate-purity factor VIII concentrates were divided into two groups. Group A consisted of 21 patients with a CD4/CD8 cell ratio of less than 1.0 and group B of 18 patients with a CD4/CD8 cell ratio of greater than 1.0. All patients of group A were switched to a high purity virus-inactivated factor VIII concentrate, whereas patients of group B continued to receive the intermediate-purity concentrate. There was no significant difference in the average decline of CD4 cells between the two groups during the observation period. 9 patients of group A and 4 patients of group B developed AIDS. 5 patients of group A but 11 patients of group B remained clinically asymptomatic. We conclude that the 15-fold increase in purity of the factor VIII concentrate had no apparent beneficial effect on the CD4 cell counts in this patient group. PMID- 1521825 TI - Electrophoretic studies on molecular defects of von Willebrand factor and platelet glycoprotein IIb-IIIa with antibodies produced in egg yolk from laying hens. AB - Immunoglobulins isolated from egg yolk (IgYs) are a convenient source of polyclonal antibodies. Their purification is simple and the yields important (50 mg immunoglobulins/egg). Nevertheless their biochemical characteristics are different from those of rabbit antibodies generally used for the study of molecular defects of plasmatic and platelet proteins. Provided standardization is achieved, IgYs can be used for immunoelectrophoresis, immunoprecipitation or immunoblotting assays. We describe here the electrophoretic and immunoblotting conditions employed to explore human plasmatic and platelet von Willebrand factor (vWF) and human platelet GP IIb-IIIa using IgYs. These two proteins are involved in primary hemostasis and their absence or abnormality is responsible for hereditary bleeding disorders. The methods were applied to the characterization of patients with vWF or GP IIb-IIIa defects and compared to classical mammalian IgG immunoelectrophoretic techniques. Results were further confirmed by flow cytometric analysis. PMID- 1521826 TI - Isolation of a fibrinolytic protease, M4, from venom of Crotalus molossus molossus (northern blacktail rattlesnake). AB - M4, a fibrinolytic protease, was isolated from the venom of Crotalus molossus molossus. It has a pI of 9.6 and a molecular weight of 27,000. The protease hydrolyzes the A alpha and B beta chains of fibrinogen, and the alpha and beta chains of fibrin. This activity was inhibited by EDTA and restored by Ca2+ or Zn2+, but not Mg2+. The protease hydrolyzed hide power azure and casein, but it had no effect on collagen, hyaluronic acid, complement or synthetic substrates for thrombin, plasmin or kallikrein. Subcutaneous injections into mice with doses as high as 100 micrograms did not cause hemorrhage. This protease may have therapeutic use as a thrombolytic agent. PMID- 1521827 TI - Increased prothrombin fragment 1 + 2 in type I diabetic patients. PMID- 1521828 TI - Fibrinogen Milano IV, another case of congenital dysfibrinogenemia with an abnormal fibrinopeptide A release (A alpha 16 Arg----His). AB - An abnormal fibrinogen, denoted as 'fibrinogen Milano IV', has been found in a 36 year-old woman without any bleeding manifestations or thrombotic tendency. Routine coagulation studies revealed prolonged thrombin and reptilase clotting times, very low plasma fibrinogen concentration determined by the functional assay but a normal fibrinogen concentration measured by the immunologic assay. Turbidity curves, measured following addition of thrombin to purified fibrinogen Milano IV, both in presence of calcium or EDTA, were markedly delayed. Release of fibrinopeptide B by thrombin was normal, whereas only half the normal amount of fibrinopeptide A was cleaved. The fibrinopeptide A peak of fibrinogen was preceded by an abnormal fibrinopeptide A*. Both peaks were collected for amino acid analysis which showed an exchange of arginine by histidine in position 16 of the A alpha chain of the fibrinopeptide A*. PMID- 1521829 TI - Safety evaluation of dibenzyl ether. AB - Dibenzyl ether (FEMA No. 2371, CAS No. 103-50-4) was given in the diet to rats at a rate of 62, 196 or 620 mg/kg/day for 91 consecutive days. Body weights and food consumption were measured weekly; haematological, clinical chemistry and urinalysis values were obtained at wk 6 and 12. Gross and microscopic pathological changes were observed and organ weights recorded. The high-dose females had increased absolute and relative liver weights; this was considered to be related to dose. Other statistically significant events that occurred sporadically within the test groups were unrelated to dose and were considered to be normal adaptive change. No toxicological or pathological effects were noted at any of the dose levels after 91 consecutive days of feeding dibenzyl ether. A no effect level was achieved at 196 mg/kg/day. In a 60-kg human, this would be equivalent to approximately 11.8 g/day, assuming a direct relationship between dose and body weight across species. Based on the possible average daily intake of 19.2 mg/day, this would confer a safety factor of 600. The safety factor based on the more realistic consumption per capita of 23.6 micrograms/day would be approximately 500,000. PMID- 1521830 TI - A 28-day feeding study with ethyl acetoacetate in rats. AB - Ethyl acetoacetate encapsulated in gum arabic was administered in rodent diet for a minimum of 28 consecutive days to groups of 16 male and 16 female rats (Sprague Dawley strain) at levels of approximately 100, 300 and 1000 mg/kg body weight/day. A further group of 16 male and 16 female rats was given rodent diet containing gum arabic as a control. The administration of ethyl acetoacetate in the diet did not adversely affect the growth or general health of the animals or their food intakes. None of the minor variations observed in the haematology, serum chemical analyses or urine analyses are considered to be indicative of a treatment-related toxic effect. Caecal enlargement was seen in male rats treated with the top dose of ethyl acetoacetate, but this was accompanied by a normal histopathology. Few histopathological abnormalities were observed. Proteinaceous casts were found in the bladder of approximately half the male rats given 1000 mg ethyl acetoacetate/kg, and nephrocalcinosis was a common occurrence in female rats in this dose group. Renal function was unimpaired in treated male and female rats, and the histopathological findings are common in the strain of rats chosen for this study. Although the caecal enlargement and the changes in kidney and bladder of rats given 1000 mg ethyl acetoacetate/kg are noted, it is considered that ethyl acetoacetate did not produce treatment-related adverse effects in rats during this study. PMID- 1521831 TI - Metabolism of an imidazole fungicide (prochloraz) in the rat after oral administration. AB - The metabolic fate and pathway of the imidazole fungicide prochloraz (1-[N-propyl N-2-(2,4,6-trichlorophenoxy) ethyl carbamoyl] imidazole) were investigated in the rat after administration of oral single doses with radiolabelled molecules. At both dose levels (50 and 250 mg/kg body weight), virtually all of the ingested [14C-phenyl]prochloraz was excreted in the urine or faeces within 96 hr, the bulk of excretion occurring between 24 and 48 hr after dosing. Urinary elimination accounted for 61 and 68% of the respective initial doses. Urinary metabolic products were isolated and identified by thin-layer chromatography, gas chromatography or gas chromatography coupled with mass spectrometry analysis. Prochloraz was completely metabolized with no unchanged compound being excreted in the urine. The main biotransformation products in rat urine were 2,4,6 trichlorophenoxyacetic acid and its corresponding alcohol, the latter as a glucuronic acid conjugate. Ring hydroxylation also occurred, with the hydroxy 2,4,6-trichlorophenoxyethanol and hydroxy-2,4,6-trichlorophenoxyacetic acid metabolites excreted in small amounts in the urine. 2,4,6-Trichlorophenol and unconjugated 2,4,6-trichlorophenoxyethanol were identified as minor urinary metabolites. PMID- 1521832 TI - A comparative study of micronucleus frequency in peripheral blood lymphocytes of human subjects given dietary cis, trans and saturated fat. AB - The micronucleus test using peripheral blood lymphocytes has been used to study the clastogenic effects of saturated, cis or trans fatty acids in human volunteers. Consumption of diets rich in either saturated fats (palmitic acid), monounsaturated cis fats (oleic acid) or monounsaturated trans fats (elaidic acid) for 3 wk had no effect on either the number of micronuclei or the frequency of micronucleated cells in lymphocytes in culture. This study adds to the accumulating body of evidence to suggest that dietary intake of trans fatty acids is not especially linked to genetic damage. PMID- 1521833 TI - Effects of indole-3-carbinol on biotransformation enzymes in the rat: in vivo changes in liver and small intestinal mucosa in comparison with primary hepatocyte cultures. AB - Groups of male Wistar rats were fed semi-synthetic diets containing 0, 200 or 500 mg indole-3-carbinol (13C)/kg for 2, 7, 14 or 28 days. After 2 days, P-450 activities were already induced, but the isoenzyme pattern induced was different in the liver and the small intestine. Hepatic P4501A1, P4501A2 and P4502B1 apoprotein levels were dose-relatedly enhanced, whereas in the small intestine induced levels of P4502B1 and P4501A1 were detected but P4501A2 was not induced. Pentoxy- and ethoxyresorufin dealkylation (PROD and EROD) were dose-relatedly enhanced in the liver (5- and 7-fold, respectively, in the higher dose group) as well as in the small intestine (8- and 13-fold, respectively, at 500 mg 13C/kg diet). Testosterone 16 alpha- and 16 beta-hydroxylation in the small intestine were enhanced (6-9-fold) from day 2 onwards, but in the liver these activities were only slightly enhanced from day 7 onwards. Thus, the major forms induced in the liver appear to be P4501A1, P4501A2, P4502B1 and, to a lesser extent, P4503A, whereas in the small intestine all of the effects that were found are associated with only one cytochrome P-450, P4502B1. After 2 days I3C (500 mg/kg) induced glutathione S-transferase in the liver (1.3-fold) and small intestine (1.5-fold). Hepatic glucuronyl transferase (GT1) was induced (about 1.6-fold) after 7, 14 and 28 days. DT-diaphorase was induced in the liver (2.7-fold) and small intestine (1.5-fold) after 14 days of exposure to 500 mg I3C/kg diet. Treatment of rat hepatocytes with indole-3-acetonitrile and 3,3'-diindolylmethane, but not I3C and indole-3-carboxaldehyde, enhanced EROD activity and halved testosterone 16 alpha- and 2 alpha-hydroxylation. All four indoles slightly induced glutathione S transferase in cultured hepatocytes. Thus, the in vitro studies suggest that the in vivo effects of I3C have to be attributed to indole-condensation products, such as 3,3'-diindolylmethane, but not to I3C itself. PMID- 1521834 TI - Comparison of cereal-based diet with purified diet by short-term feeding studies in rats, mice and hamsters, with emphasis on toxicity characteristics. AB - Animal diets used in toxicity studies are prepared either from natural ingredients (cereal-based diet) or from more refined products (purified diet). The type of diet may influence both the outcome of the study and the values obtained with the various parameters in test and control animals. To detect the parameters sensitive to changes in diet composition, short-term (4-wk) studies were conducted in rats, mice and hamsters fed either a cereal-based diet or the AIN-76A purified diet supplemented with vitamins and minerals at the highest recommended levels for each of the species used. Although the purified diet was more palatable to rats and showed a higher protein quality, growth rate and food intake were generally slightly higher with the cereal-based diet in each of the species examined. The haematological values of the two diet groups were generally comparable. On the cereal-based diet the production of faeces was considerably higher than on the purified diet and was accompanied by a higher weight of the caecum. These findings were attributed to the relatively high level and mixed composition of the fibre fraction in the cereal-based diet. Blood levels of cholesterol and phospholipids were clearly lower on the cereal-based diet than on the purified diet. Because the differences were probably due to the level and composition of the fibre fraction, they support the suggestion to replace the 5% cellulose of the AIN-76A diet by a higher level of a more composite but well defined source of dietary fibre. PMID- 1521835 TI - Dose-dependent effects of dietary phytosterol on epithelial cell proliferation of the murine colon. AB - Phytosterols are a group of compounds in plants that have been found to inhibit tumour development and decrease enhanced colonic epithelial cell proliferation in carcinogen-treated rats. The mechanism by which phytosterols may inhibit tumour development and alter cell proliferation is unknown. However, studies have shown that dietary phytosterol intake may alter levels of certain promoters in the colonic lumen, leading to altered levels of colonic epithelial cell proliferation. In this study, the effect of dietary phytosterol on the proliferative status of the intestinal epithelium was investigated in mice. Inbred C57B1/6J mice were fed semi-synthetic diet (control); 0.1% cholic acid, 0% phytosterol (cholic acid control); and cholic acid plus 0.3, 1.0 or 2.0% phytosterol. Dietary cholic acid significantly increased colonic epithelial cell proliferation and the highest labelled cell position by 92 and 35%, respectively. Phytosterol significantly reduced the enhanced labelling index and the position of the highest labelled cell in a dose-dependent manner. Mitotic index was also reduced significantly by phytosterol but not in a dose-dependent manner. The results of this study indicate that phytosterol influences the colonic epithelial cell morphometrics, that are important preneoplastic events in colon carcinogenesis, and may thus contribute to a reduced risk of cancer. PMID- 1521836 TI - Proteins and amino acids as scavengers of nitrite: inhibitory effect on the formation of nitrosodimethylamine and diazoquinone. AB - Protein and its components in high concentrations similar to those found in the digestive tract effectively scavenged nitrite and thus inhibited the formation of mutagens from nitrite. Various amino acids at 100 mM, bovine serum albumin (BSA) and trypsinized casein at 100 mg/ml effectively decreased the nitrite level of 50 mM-nitrite solution at pH 3 and 37 degrees C. Most, but not all, amino acids can convert nitrite into nitrogen gas; Pro can be converted into non-mutagenic nitrosoproline, CySH to S-nitrosocysteine, Trp to weakly mutagenic nitrosotryptophan and Tyr to non-mutagenic diazotyrosine. BSA was cross-linked, probably owing to the reaction of Tyr and Lys residues. Most amino acids inhibited more than 50% of nitrosodimethylamine formation in the reaction between 200 mM-dimethylamine and 50 mM-nitrite at pH 3 and 37 degrees C; BSA inhibited 50% of nitrosodimethylamine formation, and trypsinized casein, 100%. Most amino acids inhibited more than 50% of p-diazoquinone formation in the reaction between 25 mM-phenol and 100 mM-nitrite at pH 3 and 37 degrees C; BSA inhibited 80%, and trypsinized casein, 95% of such formation. Trypsinized casein effectively inhibited the development of the mutagenic effects attributable to the formation of diazobamethan from bamethan and nitrite. PMID- 1521837 TI - Genotoxicity studies of the food additive ester gum. AB - Ester gum (EG) is used in citrus oil-based beverage flavourings as a weighting or colouring agent. In the present study, concentrations of 50, 100 and 150 mg/kg body weight were administered orally to male Swiss albino mice, and sister chromatid exchange and chromosomal aberration were used as the cytogenetic endpoints to determine the genotoxic and clastogenic potential of the food additive. Although EG was weakly clastogenic and could induce a marginal increase in sister chromatid exchange frequencies, it was not a potential health hazard at the doses tested. PMID- 1521838 TI - Effects of isopropanol on the development of inflammatory reactions in rats. AB - The effects of isopropanol on the development of inflammation were studied in rats. Isopropanol inhibited both the histamine-induced increase in cutaneous vascular permeability and the carrageenan-induced plasma exudation into the pleural cavity. The lipopolysaccharide-induced leucocyte emigration into the subcutaneous pouch was unaffected by isopropanol, but the leucocyte emigration of carrageenan-induced pleural inflammation was markedly inhibited by isopropanol. In contrast, when isopropanol was administered with an anti-inflammatory drug (indomethacin or dexamethasone), it enhanced the pleural inflammatory reaction. These results suggest that isopropanol may exert toxic effects through interference with the normal processes of inflammation and interaction with other agents that affect inflammatory reactions. PMID- 1521839 TI - A compilation of genotoxicity and carcinogenicity data on aromatic aminosulphonic acids. AB - A review is presented to evaluate existing information on genotoxicity and carcinogenicity testing of various aromatic aminosulphonic acids (AASAs). A great variety of water-soluble azo dyes can form aromatic phenyl- or naphthyl aminosulphonic acids by chemical and enzymatic reduction. AASAs are also used as intermediates in the synthesis of azo dyes and azo pigments and can arise as contaminants in the final products. Comparisons have been made with the data available on the corresponding unsulphonated analogues, some of which are known to be genotoxic and/or carcinogenic. The vast majority of the AASAs were conclusively non-mutagenic in the Ames test. In most cases the absence of genotoxicity was also demonstrated with a variety of other test systems in vitro and in vivo. It is concluded that AASAs, in contrast with some of their unsulphonated analogues, generally have no or very low genotoxic and tumorigenic potential. PMID- 1521840 TI - [Treatment with oral contraceptives. Swiss consensus conference on frequently discussed questions about hormonal contraception]. PMID- 1521842 TI - [Criteria for evaluating consensus development conferences in medicine]. PMID- 1521841 TI - [Spontaneous dissection of the internal carotid artery]. AB - A typical case history of spontaneous dissection of the internal carotid artery is presented. In young patients with cerebral ischemia, initial pain in the affected side of the head and neck, a possible provocative mechanism and a transient or even persistent Horner's syndrome are highly suggestive. The angiographic picture of carotid artery dissection is characteristic. Spontaneous resolution is common, and recurrence rare. Surgical treatment can therefore be reserved for individual cases with recurrent ischemia and caused by emboli originating in the dissected segment of the artery. PMID- 1521843 TI - On the dangers of invisibility... PMID- 1521844 TI - The experience of bereavement in caregivers of family members with Alzheimer's disease. AB - This paper reports an analysis of the bereavement experience described by 13 caregivers of family members with Alzheimer's disease. Utilizing the constant comparative method, four patterns of experience and two major concepts describing bereavement were identified. Two stages of bereavement are described: The first during caregiving and the second following the death of the family member. Findings support the need for professional intervention for caregivers during the caregiving period, which may also be a time of intense bereavement. PMID- 1521845 TI - Men's views about hysterectomies and women who have them. AB - Men's (N = 25) views about the effects of hysterectomy on women and on their relationships with women they knew who had experienced hysterectomies were solicited by interviews. Many men were not knowledgeable about hysterectomy. They perceived negative psychological, social and sexual effects of hysterectomy on women; but they did not think hysterectomy affected their relationships with women. However, they also communicate very little with women or health care professionals about hysterectomy. PMID- 1521846 TI - Health policy dilemmas related to high technology infertility services. AB - As cost containment in health care becomes an important concern, the costs and benefits of specific health care services will be more closely examined. The costs and benefits of one type of health care, high technology infertility services, are explored in this paper. These services may be particularly susceptible to cost containment since they are costly, raise ethical issues, and because they currently are provided to healthy individuals not experiencing life threatening illness who can afford them. PMID- 1521847 TI - Ethical concerns in a long-term tube feeding study. AB - Five ethical concerns about decision-making in relation to tube feeding were determined through secondary analysis of findings from a chart review study examining long-term tube feeding practices. The five ethical concerns are: (1) who should make the decision to tube feed? (2) how should tube feeding decisions be made? (3) what are valid reasons for initiating and continuing tube feeding? (4) is it permissible to withdraw tube feeding once it is initiated? and (5) is tube feeding an effective and appropriate life supporting technology? Ethical concerns are described, using examples from research data. Implications for health care follow. PMID- 1521848 TI - Functional status outcomes of a nursing intervention in hospitalized elderly. AB - This paper examines the effectiveness of a nursing intervention for elderly hospitalized patients (N = 235) as measured by functional outcomes. A nursing intervention targeted at factors which influence acute confusion or delirium employed strategies to educate nursing staff, mobilize patients, monitor medication and make environmental and sensory modifications. Subjects who received the intervention were more likely to improve in functional status from admission to discharge than subjects who did not receive the intervention. PMID- 1521849 TI - Conceptualizing psychological well-being in cognitively-impaired older persons. AB - This article addresses a neglected area within nursing knowledge development: appropriate conceptual frameworks for guiding care of institutionalized, cognitively-impaired elders. Following a review of possible conceptual frameworks, psychological well-being, as defined by Lawton (1983), is proposed as an appropriate framework for guiding knowledge development and care of this elderly population. Two aspects of psychological well-being, positive and negative affect, may be appropriate indicators of the concept in cognitively impaired elders. Instruments for measurement of psychological well being are also discussed. The implications of using psychological well-being as a conceptual basis for both research and nursing care are presented. PMID- 1521850 TI - Postpartum depression: a nursing perspective on women's health and behaviors. AB - Postpartum depression is examined from different disciplinary perspectives including obstetrics, psychiatry, psychology and nursing. These perspectives are compared in relation to knowledge development, research designs and interventions for clinical practice. Nursing's contributions to understanding women's health and behaviors are highlighted in three areas: exploring women's experiences with symptoms of depression; delineating the character of women's affective changes during childbearing; and further study of another form of symptom distress conceptualized as dysphoria. Three alternative hypotheses are presented as new directions for future nursing research. PMID- 1521851 TI - The evolutionary spiral of a specialized center for women's health research. PMID- 1521852 TI - The application of motivational theory to cardiovascular risk reduction. AB - The level of motivation sustained by an individual has been identified as a primary predictor of success in sustained cardiovascular risk factor modification efforts. This article reviews the primary motivational theories that have been used to explain and predict cardiovascular risk reduction. Specifically, the application of the Health Belief Model, Health Promotion Model, Theory of Reasoned Action, Theory of Planned Behavior and Self-efficacy Theory to the initiation and maintenance of cardiovascular health behavior is addressed. The implication of these theories for the development of nursing interventions as well as new directions for nursing research and practice in the study of individual motivation in health behavior change are discussed. PMID- 1521853 TI - Registering the history of nursing. PMID- 1521854 TI - The imposter phenomenon in the clinical nurse specialist role. PMID- 1521855 TI - The imposter phenomenon in the clinical nurse specialist role. PMID- 1521856 TI - The imposter phenomenon in the clinical nurse specialist role. PMID- 1521857 TI - The imposter phenomenon in the clinical nurse specialist role. PMID- 1521858 TI - P-aminodiphenylamine induced biochemical changes in sex organs of male albino rats. AB - Intraperitoneal administration of p-aminodiphenylamine (p-ADPA), an aromatic amine of wide industrial applications, / 42.5 mg/kg body weight for 180 days significantly decreased the activities of testicular lactate dehydrogenase and hyaluronidase and lactic acid content indicating arrest of spermatogenesis. Patchy necrosis of the testis was confirmed histopathologically. No change in testicular cholesterol, fructose content of coagulating glands and dorso-lateral prostate and activities of alkaline phosphatase in seminal vesicle and acid phosphatase in ventral prostate support normal androgenic status. PMID- 1521859 TI - Electrokinetic energy conversion studies of urine-oxalic acid systems across urinary bladder membrane. AB - Electrokinetic studies of urine-oxalic acid systems with increasing concentration of oxalic acid in urine have been carried out across urinary bladder membranes. It has been found that electro-osmotic flux and streaming current decrease with increase in concentration of oxalic acid in urine while hydrodynamic flux and streaming potential increase with increase in concentration. Kinetic energy term (alpha 1) and polarizability term (alpha 2) have been computed for these systems and it has been found that polarizability decreases much faster with increase in concentration of oxalic acid in urine. Electrokinetic energy conversion of these systems have been computed and it has been found that electrokinetic energy conversion is maximum for urine and it decreases with increase in concentration of oxalic acid in urine. Poor energy conversion may lead to sluggish flushing action which may ultimately lead to formation of urinary calculi in the bladder and so present study may be of some use in predicting electrophysiology of the bladder. PMID- 1521860 TI - Uranyl nitrate induced corpuscular derangement: an early indication of induced acute renal failure. AB - Erythrocyte structure was studied in rat after uranyl nitrate (UN:5 mg/kg) intoxication. The study of pathogenic progression of UN induced renal failure (ARF) was confined to the early initiation phase (2 hr), late initiation phase (8 hr) and the maintenance phase (24 hr). Erythrocyte structure has been found to be greatly influenced. The UN induced hemolytic syndrome/hypoxia was accompanied by a marked anisocytosis and poikilocytosis during different phases of ARF, which is characteristic of UN poisoning. Subsequent alterations in erythrocyte structure followed by UN administration or during the pathogenic progression of ARF has clinical and diagnostic importance as the alterations were much distinct prior to the clinical manifestation of ARF even at light microscopic level. PMID- 1521861 TI - Changes in levels of lipid peroxides and activity of superoxide dismutase and catalase in diabetes associated with myocardial infarction. AB - Studies were carried out on the metabolism of lipid peroxides and antioxidative enzymes during diabetes and diabetes superimposed with myocardial infarction. Diabetes was induced using alloxan and myocardial infarction was induced by isoproterenol. In the case of diabetic animals there was a decrease in the levels of lipid peroxides in the heart while in the case of diabetes associated with myocardial infarction it was slightly elevated. The activity of superoxide dismutase and catalase showed a decrease in both the groups. Glutathione showed a fall in the case of diabetes and diabetes associated with myocardial infarction while taurine in heart and ceruloplasmin in the serum was elevated. Histopathological changes in the heart tissue showed some focal changes in the case of both diabetes and diabetes associated with myocardial infarction, but the degree of necrosis was much less than in the case of myocardial infarction. PMID- 1521862 TI - Hypolipidemic activity of Achyranthus aspera Linn in normal and triton induced hyperlipemic rats. AB - The alcoholic extract of A. aspera, at 100 mg/kg dose lowered serum cholesterol (TC), phospholipid (PL). triglyceride (TG) and total lipids (TL) levels by 60, 51, 33 and 53% respectively in triton induced hyperlipidemic rats. The chronic administration of this drug at the same doses to normal rats for 30 days, lowered serum TC, PL, TG and TL by 56, 62, 68 and 67% respectively followed by significant reduction in the levels of hepatic lipids. The faecal excretion of cholic acid and deoxycholic acid increased by 24 and 40% respectively under the action of this drug. The possible mechanism of action of cholesterol lowering activity of A. aspera may be due to rapid excretion of bile acids causing low absorption of cholesterol. PMID- 1521863 TI - Antimicrobial activities of mycotoxin MT81 and its structural derivatives. AB - Antimicrobial activities of mycotoxin MT81 and its acetylated, benzoylated and acetic acid derivatives were determined by zone inhibition method. MT81, acetylated MT81 and acetic acid MT81 exhibited sensitivity (31.25, 62.50, 62.50 micrograms/ml respectively) to all the test bacteria. Benzoylated-MT81 did not exhibit any activity even up to 1000 mcg/ml. MT81, its acetylated and acetic acid derivatives exhibited antifungal activity up to 62.5 micrograms/ml and 125.0 micrograms/ml respectively against test yeasts and other fungi. Benzoylated MT81 also exhibited antifungal activity but the degree was comparatively less. PMID- 1521864 TI - Indole 3-acetic acid production by ectomycorrhizal fungi. AB - Ability of 8 ectomycorrhizal fungi to synthesise indole 3-acetic acid from L tryptophan and their growth rate were studied. Differences in the levels of IAA synthesis and biomass production among the 8 mycorrhizal fungi were observed. A positive correlation was recorded between IAA level and mycelial growth. The synthesis of IAA and mycelial biomass were maximum on 30th day after incubation. Pisolithus tinctorius and Laccaria laccata exhibited higher amounts of IAA production than other fungi, whereas Amanita muscaria and Rhizopogon luteolus showed least quantity of IAA. PMID- 1521865 TI - Cholesterol and lipid peroxidation in 3 beta-(2-diethylaminoethoxy)- androst-5-en 17-oneHCl (U18666A) induced cataractogenesis in rats. AB - Decrease in cholesterol was observed in precataractous, cataractous, advance nuclear cataractous and non-cataractous lenses when 3 beta-(2-diethylaminoethoxy) androst-5-en-17- oneHCl (U18666A) was injected, sc, to rats. Significant increase in lipid peroxidation was observed before the onset of any apparent lenticular opacity in U18666A treated rats. The results suggest that decrease in cholesterol is capable of altering the structural integrity of lens fibers. However, 12.5% decrease in cholesterol and 5% increase in lipid peroxidation observed in non cataractous lenses indicated that these changes are not sufficient for any apparent opacification. PMID- 1521867 TI - Hepatitis C virus is transmitted from mother-to-child. PMID- 1521868 TI - Mutations at codon 717 of the beta-amyloid precursor protein gene are a cause of Alzheimer's disease. PMID- 1521866 TI - Effect of antimicrobials on cholesterol synthesis and content in liver and small intestines. AB - The antimicrobials tetracycline, ampicillin and bactrim (cotrimoxazole) decreased HMG CoA reductase activity in liver and small intestines of albino rats. Diminished incorporation of 1, 2, 14C acetate into cholesterol of small intestines in bactrim group was noted. There was a significant fall in cholesterol content of liver, duodenum, jejunum and ileum of the bactrim group and jejunum only in tetracycline group. PMID- 1521869 TI - Thyroid in intermediary metabolism of the migratory redheaded bunting, Emberiza bruniceps (Brandt). AB - Effect of thyroidectomy and replacement therapy with L-T4, on liver and plasma biochemical constituents of E. bruniceps, was studied during January (recovery phase). Thyroidectomy elevated significantly the levels of plasma glucose, protein, cholesterol, diglyceride, hepatic cholesterol and depressed significantly hepatic free fatty acid without affecting liver and body weights. Treatment of thyroidectomized birds with L-T4 restored liver and plasma constituents, but had significantly depressed plasma phospholipid. These findings suggest that thyroid hormones are critically involved in lipo-regulatory mechanism(s) in E. bruniceps. PMID- 1521870 TI - Circadian features of carbohydrate metabolism in domestic fowls exposed to weekly 120 degree-shifts of synchronizer schedule. AB - Effects of weekly 8 hr advance- or delay-shifts on the circadian rhythm of plasma glucose, liver glycogen and muscle glycogen in male domestic fowls, beginning at about 3 days of age, were examined. Circadian rhythm in the aforesaid indices of carbohydrate metabolism in control birds was also studied. Blood and tissue samples were collected from birds in all the three groups at 4 hr intervals over a single 24 hr time scale both at 6th and 12th week of age. Plasma glucose and glycogen content in the tissues were determined by employing standard techniques. Cosinor rhythmometry was used for analyzing time series data. In general, a statistically significant circadian rhythm was documented for all the three indices in control and advance-schedule birds, irrespective of age. In contrast, in delay-schedule birds, statistically significant circadian rhythm could not be detected, excluding in muscle glycogen at 12th week of age. The poor growth rate in the delay-schedule birds could be imputed to the disappearance of circadian rhythm in the indices of carbohydrate metabolism. PMID- 1521871 TI - Ontogenetic and comparative analysis of LDH isozymes in the three species of Indian major carp. AB - Expression patterns of lactate dehydrogenase (LDH) isozyme were investigated in embryonic and post embryonic stages of Labeo rohita, Cirrhinus mrigala and Catla catla using starch gel electrophoresis. Species specific and differential enzyme locus (gene) expression patterns were found in LDH up to 18th hr of study. The isozyme up to 36th hr after fertilization seemed to be completely active and showed electrophoretic patterns very similar to those of the adults. Comparative analysis of the isozyme of the three species permitted species identification even during the embryonic stages when it is impossible to identify on morphological characters only. Also, the genetic studies indicated different taxonomical and evolutionary histories of the species. PMID- 1521872 TI - Isolation and characterization of an analogue-resistant aminoacyl-tRNA synthetase mutant in Aspergillus nidulans. AB - Six mutants resistant to p-fluorophenylalanine (FPA) were selected on a medium containing aspartate as the sole source of nitrogen using a phenylalanine requiring (phenA)auxotroph of A. nidulans as the wild type. The mutants, on the basis of genetic characterization, were found to be alleilic and located on the left arm of the linkage group III, approximately 13 map unit left to meth H locus, henceforth assigned to the symbol fpaV. At a fixed concentration of phenylalanine (23 micrograms/ml), the LD50 value of FPA for all the six mutants was found to be about three times more than that for the wild type strain. Affinity chromatographic purification of the enzyme phenylalanyl-tRNA (Phe-tRNA) synthetase from the mutant as well as the wild type strains, revealed that the wild type enzyme had about 1.4-fold higher affinity for phenylalanine as compared to that for FPA, both in the affinity column and in the catalytic reaction. However, the mutant enzyme showed almost a similar affinity for both in columns but a greatly reduced affinity for FPA in the catalytic reaction. PMID- 1521873 TI - Inactivation of a beta-glucosidase from Arthrobotrys conoides by diethyl pyrocarbonate: evidence of histidine at the active site. AB - Modification of A. conoides beta-glucosidase by diethylpyrocarbonate caused rapid inactivation of the enzyme. The kinetic analyses showed that the inactivation by diethylpyrocarbonate resulted from the modification of an average of one histidine residue per mole of enzyme. The modified enzyme showed an increase in absorbance at 240 nm. Sulphydryl, lysine and tyrosine residues were not modified by diethylpyrocarbonate treatment. The substrate offered significant protection against diethylpyrocarbonates modification. The results indicate that diethylpyrocarbonate was interacting with the enzyme at or near the active site. PMID- 1521874 TI - Comparison of single breath and steady state methods for the measurement of pulmonary diffusing capacity for carbon monoxide in normal subjects, patients with bronchial asthma and chronic obstructive airway disease. AB - The results of pulmonary diffusing capacity (DLCO) measurements by the steady state (DLCOss) and single breath (DLCOsb) methods were compared in 50 normal subjects (Group A), 50 patients with bronchial asthma (Group B) and 50 patients with chronic obstructive lung disease (COAD) (Group C). A significant correlation was observed between DLCOss and DLCOsb in all the three groups of subjects. This relationship was stronger in Groups A and B as compared to Group C. Both DLCOsb and DLCOss were significantly correlated to parameters of air-flow obstruction. Both measurements of DLCO appear valid in normal subjects and in patients with bronchial asthma. In patients with COAD, on the other hand, DLCOsb may be valid measurement, since it is less likely to be influenced by airways obstruction. PMID- 1521875 TI - Role of corticosteroids in the management of chronic obstructive lung disease: factors predicting response. AB - A double-blind crossover trial of prednisolone was conducted in 70 patients of chronic obstructive lung disease (COLD). Emphysema dominated the clinical picture in 38, rest being chronic bronchitis with varying degrees of air trapping. None of the patients had clinical asthma. All the patients had obtained maximal benefit from an optimal dose of bronchodilators prior to entering the study. Prednisolone in a dose of 0.8 mg/kg was prescribed in a double blind crossover manner with identical appearing placebo tablets. Patients were evaluated on a weekly basis for an objective as well as a subjective response and side effects of therapy. Thirty-four patients demonstrated a statistically significant improvement in pulmonary functions. In 20 others only subjective response was observed. A good objective response was predicted by a pre-study variability in FEV1, disease duration of less than 10 years and a history of smoking less than 50 pack years. PMID- 1521876 TI - A study on the prevalence of chronic bronchitis in workers exposed to smoke and irritant fumes in a railway workshop. AB - In the present study 108 full time workers employed in various sections of a railway workshop and exposed to smoke and irritant fumes, and 45 matched control subjects from local administrative staff were investigated to find prevalence of chronic bronchitis. In all 18 (16.7%) workers and 4 (8.9%) control subjects had clinical evidence of chronic bronchitis. Peak expiratory flow rate less than 300 L/min was observed in 54.6% workers and 2.2% control subjects. A significantly higher prevalence of chronic bronchitis was seen in workers. The advancing age, smoking and duration of exposure had significant influence on prevalence of chronic bronchitis. PMID- 1521877 TI - Pneumonia left lung: an unusual presentation of tropical pulmonary eosinophilia. PMID- 1521878 TI - Re-expansion pulmonary edema and hypotension. AB - A case with diagnosis of non-Hodgkin's lymphoma and superior vena cava obstruction on chemotherapy, presented with respiratory distress and massive pleural effusion of right hemithorax. On removal of 3.5 litres of fluid, he developed pulmonary edema of the same side and hypotension. PMID- 1521879 TI - Pneumoconiosis in an Indian slate-pencil factory worker. AB - A male slate-pencil factory worker who inhaled dust for 10 years came to our hospital with complaints of breathlessness of two months duration. He developed massive fibrotic lesions in both lungs but was not diagnosed earlier due to the absence of symptoms. PMID- 1521880 TI - False positive acid-fast bacilli smears. PMID- 1521881 TI - Airway obstruction in bronchiectasis and its reversibility--a study of 38 patients. AB - Thirty-eight patients (20 males and 18 females) with bronchiectasis were studied for the evidence of airway obstruction and its reversibility in response to subcutaneous terbutaline. There was an improvement in VC (8.56%), FEV1 (6.36%), PEFR (15%) and PEF 25-75% (18%) respectively. The difference being statistically significant in VC and highly significant in FEV1, PEFR and FEF25-75 as compared to initial values and in 6 patients the improvement in FEV1 was more than 15%. The improvement in airway obstruction was not related to the character of expectoration. It is suggested that all the patients of bronchiectasis should be assessed for the reversibility of airway obstruction and those showing a reversible pattern be treated accordingly. PMID- 1521882 TI - New vaccines against hepatitis A enter the market--but who should be vaccinated? PMID- 1521883 TI - A seroepidemiologic study of hepatitis A in Spanish children. Relationship of prevalence to age and socio-environmental factors. AB - Three child population groups from the Madrid area were studied for anti-HAV antibodies. Analysis was carried out with respect to age and socio-environmental factors. The population understudy was composed of 156 children, with ages ranging from 1 to 14 years; they were stratified in three socio-environmental groups (white-family unit, gypsy-family unit and orphanage), and also divided into subgroups according to age. As a whole, an age-related increase in prevalence was found. The overall seroprevalence by socio-environmental groups was: gypsy-family unit 63%, orphanage 46%, and white-family unit 23%. Significant differences between groups appeared from seven years on, being more marked among the eldest subgroups. Among the factors evaluated, hygienic-sanitary conditions and overcrowding influenced the high prevalence rate found in the gypsy-family unit subjects, whereas overcrowding appeared to be responsible for the higher prevalence in orphanage residents, as compared to white-family unit children. PMID- 1521884 TI - Borrelia burgdorferi infection in Europe: an HLA-related disease? AB - Various studies in the United States and Europe have established human leucocyte antigens (HLA) Cw3, DR2 and DR4 as risk factors for manifest Borrelia burgdorferi infection or the development of chronic courses of Lyme disease. Other studies failed to confirm these findings. In the present study the frequencies of HLA A, B, Cw and DR were analysed in 283 persons from Austria and Germany with manifest B. burgdorferi infection. No statistically significant differences were found between patients and the control groups with regard to the frequencies of particular HLA antigens, nor were differences in antigen frequencies in the patients with manifestations of different stages of disease significant. Furthermore, a statistical re-evaluation of all the European studies failed to confirm particular HLA antigens as risk factors for B. burgdorferi infections to become manifest or chronic. PMID- 1521885 TI - Solitary borrelial lymphocytoma: report of 36 cases. AB - Thirty-six cases of borrelial lymphocytoma were detected during the period 1986 to 1990 in Slovenia. Borrelial lymphocytoma was located on the ear lobe in 17 persons, ten female and seven male, with a median age of 12 years (range 2-56). Fourteen of these 17 were children under 14 years of age. A tick bite was remembered by 15 patients a median of 30 days before borrelial lymphocytoma developed. The most frequent month of onset was September. Erythema migrans preceded or accompanied borrelial lymphocytoma in eight cases. In 15 cases, eight female and seven male, borrelial lymphocytoma was localized on the mamilla. Median age of these patients was 42 years (range 15-72). Twelve had a tick bite about 45 days (median value) before the onset of borrelial lymphocytoma, which occurred most frequently in August. Erythema migrans was reported in 13 patients and preceded borrelial lymphocytoma in ten cases. In another four patients borrelial lymphocytoma was localized on the nose, scrotum, upper arm and shoulder. Antibiotic treatment with phenoxymethyl-penicillin (n = 16), ceftriaxone (n = 8), doxycycline (n = 9), azithromycin (n = 2) and penicillin G (1) led to complete recovery within an average of three weeks in all cases. PMID- 1521886 TI - Acyclovir monotherapy versus acyclovir plus beta-interferon in focal viral encephalitis in children. AB - Severe focal viral encephalitis is most commonly caused by herpes simplex virus (HSV), but other viruses may act as etiologic agents as well. Acyclovir (ACV) is the standard therapy for HSV encephalitis, but the mortality of 28% and defect healing rate of about 35% are still unsatisfactory. Furthermore, ACV has virtually no effect on other pathogens of viral encephalitis, except for varicella-zoster virus (VZV). It is well known that beta-interferon (beta-IFN) has a broad antiviral spectrum, and it has been demonstrated in vitro that beta IFN in combination with acyclovir has synergistic inhibitory effects on HSV. To investigate if the combination of ACV with and without beta-IFN might also be of significance for the treatment of severe viral encephalitis, we performed a retrospective study. A case record form was sent to all 278 West German children's hospitals. The response rate was 78%. A total of 301 patients were reported, of whom 214 received specific antiviral therapy with either ACV alone (n = 179) or ACV plus beta-IFN (n = 35). No overall differences between ACV monotherapy and the combination therapy were observed. However, in a subgroup of 41 patients (ACV n = 30, ACV plus beta-IFN n = 11) who had low-density areas of the temporal lobes on cranial computed tomography scans, compatible with severe focal encephalitis, sequelae due to defect formation and mortality were significantly (p = 0.014) reduced in patients who had received combination therapy.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1521888 TI - Prevalence of HCV antibodies in health-care workers from northern Italy. AB - The prevalence of HCV antibodies was assessed in 407 health-care workers and in 253 control subjects by means of immunoassays based on recombinant antigens. The seroprevalence in the study group was fairly low (1.2%) and not statistically different from that of controls (0.8%). The relation of HBV and HCV infections was evaluated in 83 health-care workers and in 82 controls: in both groups anti HCV positivity was weakly related (p less than 0.05) to the HBV infection. HCV infection was associated with working in high risk wards (4/5 cases) and with report of accidental needle pricks (4/5 cases). As evaluated by means of the available markers, HCV infections in health-care workers seem to be rare. PMID- 1521887 TI - Bacteremia caused by Stomatococcus mucilaginosus: report of seven cases and review of the literature. AB - During a three-year period eight patients with blood cultures positive for Stomatococcus mucilaginosus were identified at two university hospitals. One patient without any signs of infection had a central venous catheter that was colonized with this organism, two patients had transient bacteremia without definite relationship to underlying disease, whereas the remaining five patients suffered from clinically significant infections. Of these last five patients, one had undergone prior head and neck surgery and four had hematologic malignancy with mild to severe neutropenia; two of the latter patients developed the infection subsequent to dental surgery. Besides neutropenia and mucosal damage in the oropharynx, quinolone antibacterial prophylaxis may have been an additional risk factor for the development of S. mucilaginosus bacteremia in these patients. A thorough review of the literature revealed that in addition to our findings, endocarditis and foreign body infections are further typical clinical manifestations. Although the overall antibiotic susceptibility pattern of S. mucilaginosus resembles that of streptococci, it is suggested that penicillin G may not be the drug of choice for initial therapy of particularly severe infections. S. mucilaginosus can be easily differentiated from other gram positive bacteria when certain key criteria (e.g. adherence to agar surfaces, poor growth on Mueller-Hinton agar, presence of a capsule) as well as an array of biochemical tests, including commercially available identification systems, are applied. Our own and published data emphasize that both microbiologists and clinicians should be increasingly aware of this opportunistic pathogen. PMID- 1521889 TI - The antimicrobial spectrum of honey and its clinical significance. AB - The antimicrobial spectrum of honey was investigated by placing two drops into each of the wells made on culture media on which pure cultures of various organisms obtained from surgical specimens were grown. The organisms were grown under both aerobic and anaerobic environments. Fungal cultures of common fungi causing surgical infections or wound contaminations were mixed with 100%, 50% and 20% unprocessed honey. Growth inhibition was complete in the media containing 100%, partial in media containing 50% and no inhibition was produced by 20% honey. Unprocessed honey inhibited most of the fungi and bacteria causing wound infection and surgical infection except Pseudomonas aeruginosa and Clostridium oedematiens. Apart from Streptococcus pyogenes which is only moderately inhibited, golden syrup, a sugar syrup with similar physical properties as honey, did not inhibit any of the bacteria or fungi tested, demonstrating that honey is superior to any hypertonic sugar solution in antimicrobial activity. Honey is thus an ideal topical wound dressing agent in surgical infections, burns and wound infections. PMID- 1521890 TI - Temporofacial zygomycosis in a pregnant woman. AB - A 38-year-old Omani woman, seven months pregnant, developed extensive zygomycosis involving maxillary and temporal bones. No evidence of any underlying immune deficiency was detected except that which may be attributed to pregnancy. After delivery the patient was treated with repeated courses of amphotericin B, which resulted in a complete clinical resolution. Zygomycosis in uncomplicated pregnancy has not been previously described. PMID- 1521891 TI - Massive renal infarction due to mucormycosis in an AIDS patient. AB - Isolated renal infection by Mucor spp. occurs very rarely, even in the immunocompromised host. The mortality of the different forms of mucormycosis reaches 75-100% in most series. Infection of the kidney is usually diagnosed post mortem. Thus, when renal infection is recognized, aggressive treatment including surgery and amphotericin B is required. We present a case in which a massive left renal infarction was the unique manifestation of mucormycosis in an AIDS patient. Administration of amphotericin B and left nephrectomy were necessary to achieve satisfactory outcome. PMID- 1521892 TI - Delayed hepatobiliary disease and eosinophilia in atypical measles. PMID- 1521893 TI - Penicillin-resistant pneumococcus in community-acquired bacteremic pneumonia in Germany. PMID- 1521894 TI - Clinical relevance of pneumococcal antigen detection in urine. PMID- 1521896 TI - Malarial acute renal failure. PMID- 1521895 TI - Treatment of acute non-A, non-B hepatitis with interferon alpha-2b. PMID- 1521897 TI - Effect of dialyser composition and reuse on neutrophil count and elastase alpha-1 proteinase inhibitor complex formation. AB - To assess the inter-relationship of leucopenia and PMN elastase release we undertook a prospective crossover study of 6 patients dialysed with new and reused cuprophane, cellulose acetate and polysulfone membranes. Serial blood samples were analysed for PMN count, and elastase-alpha 1-proteinase inhibitor complex (E alpha 1PI) concentrations. After 15 min dialysis with new membranes median PMN counts fell by 72.2%, 25.3% and 22.1% with cuprophane, cellulose and polysulfone, respectively. With reuse the decreases were reduced to 6.4%, 8% and 13.6%. All membranes produced a gradual increase of E alpha 1PI. Median E alpha 1PI accumulation rates (ng ml-1 min-1) with new membranes were 175, 169 and 187 for cuprophane, cellulose acetate and polysulfone, respectively. With reuse of cuphrophane and cellulose acetate these rates fell to 99 and 109 (p less than 0.05 and p less than 0.05, respectively), however, with polysulfone it remained unchanged at 180 ng ml-1 min-1. This study highlights differences between two aspects of the neutrophil response to haemodialysis, and demonstrates that extrapolation from individual parameters to conclusions concerning biocompatibility may be inappropriate. PMID- 1521898 TI - Failure of blood pressure to increase following erythropoietin therapy in the renoprival status. AB - Two anephric patients in the course of one year erythropoietin therapy improved their anemic status without changes in Mean Arterial Blood Pressure. The discordant time course behaviour of hematocrit and blood pressure points to the importance of residual renal tissue for blood pressure to develop during erythropoietin therapy in the renoprival status. PMID- 1521899 TI - Mechanical bridge to transplantation with the Vienna heart in TAH and LVAD configuration. AB - The Vienna heart uses a vacuum formed, pellethane pulsatile ventricle and is available in left ventricular assist (LVAD) and total artificial heart (TAH) configurations. This device was used as mechanical support of the failing heart in nine patients intended for heart transplantation. In two patients with cardiomyopathy an orthotopic TAH was implanted; one survived despite severe preoperative ischemic liver damage, and the other died of sepsis. In seven patients an atrio-aortic LVAD was implanted; six had suffered an acute myocardial infarction with cardiogenic shock, and one could not be weaned off bypass. Three patients survived. These included one 65-year-old with incipient ARDS at operation, and a 40-year-old with preoperative liver and kidney insufficiency who was transplanted in septicemia. In this patient the septic focus, natural and artificial heart, were removed at transplantation. Four patients died. In one we were unable to establish satisfactory circulation, one died after failure of the transplanted heart, one suffered a lethal cerebral embolism and one developed multi-organ failure after repeated attacks of ventricular fibrillation. With the Vienna heart sufficient circulatory support could be established with cardiac outputs between 6 and 8 l/min for the TAH and 3.5 to 4.5 l/min for the LVAD. With this type of support an overall survival rate of 44% could be achieved. Mechanical hemolysis was not a clinical problem and no device failure occurred. PMID- 1521900 TI - Clinical effects of a sorbent suspension dialysis system in treatment of hepatic coma (the BioLogic-DT). AB - Fifteen patients with acute deterioration of liver function, high serum ammonium, and an average coma level of 3.9 were identified. Eleven of the patients were on respirator support, and eleven had kidney failure pursuant to the liver failure. The patients were treated for 8-12 hours daily with the BioLogic-DT system, in which membranes of a cellulosic plate dialyzer actively pump blood through a single access at over 200 ml/min, and the dialysate contains a suspension of powdered activated charcoal (300,000 square meters surface area) and cation exchanger (160 meq capacity). No anticoagulant was used. In spite of the declining condition of the patients prior to treatment, there was a statistically significant improvement in neurologic status during individual treatments, and a positive trend over 1-12 (average four) daily treatments. Four patients recovered liver function and another four improved enough to receive a liver transplant operation. The BioLogic-DT system appears to be safe in treatment of patients with hepatic insufficiency and coma. The neurologic improvement of these patients indicates that many toxins of hepatic failure are dialyzable across cellulosic membranes and bound by charcoal. PMID- 1521901 TI - Microcarrier culture of hepatocytes in whole plasma for use in liver support bioreactors. AB - Contact activation of plasma clotting may limit the use of some microcarrier types for hepatocyte attachment in a liver assist device. Activation by seven microcarrier types was studied in plasma containing 2-500 units heparin/mL. Clotting was activated by dextran (Cytodex 1 and 2) and collagen-coated (Cytodex 3) microcarriers at 2-25 units/mL (Cytodex 1) and 2-100 units/mL (Cytodex 2 and 3). There was no activation by polystyrene, gelatin, glass or fibronectin-coated polystyrene microcarriers. Compared with culture medium, incubation of HepG2 cells in plasma did not affect cell viability but increased cell number (56.4 versus 65.1 x 10(4) cells; P less than 0.05) and incorporation of [3H]-amino acids into protein (204913 versus 279624 dpm; P less than 0.05). Polystyrene attached cells demonstrated time-linear protein synthesis, glucose and 7 ethoxycoumarin metabolism. We conclude that polystyrene-attached hepatocytes maintain viability and metabolic activity in plasma and are of potential use in a liver support bioreactor. PMID- 1521902 TI - Spontaneous dialytic ultrafiltration with intraperitoneal reinfusion of the concentrate in 15 cirrhotic patients with intractable ascites. AB - The clinical efficacy and tolerance of dialytic ultrafiltration of ascites through a hemofilter (DUF) with peritoneal reinfusion of the concentrate was evaluated in 15 cirrhotic patients with intractable ascites. All together, 51 DUF procedures were carried out. An average of 8.6 was ultrafiltered during 12 h with no significant change in blood pressure, hemoglobin, coagulation parameters or plasma creatinine. A significant increase in ascitic protein concentration was observed immediately after the procedure and a slight but significant increase in 24 h urinary output. A controlled evaluation of DUF compared to large paracenteses seems to be justified by these preliminary results. PMID- 1521903 TI - Plasma exchange treatment in rapidly progressive glomerulonephritis associated with anti-neutrophil cytoplasmic autoantibodies. AB - This study reports on 12 patients with acute renal failure due to biopsy-proven rapidly progressive glomerulonephritis and signs of systemic disease in whom antineutrophil cytoplasmic autoantibodies (ANCA) were detected by indirect immunofluorescence (IIF) on alcohol-fixed neutrophils and assessed in serial determinations by ELISA. The diagnosis was: Wegener's granulomatosis in nine patients who showed a diffuse cytoplasmic pattern at IIF (c-ANCA), and microscopic polyarteritis in three where a perinuclear pattern (p-ANCA) was seen. All patients underwent a course of plasma exchange - PE - (3-10 sessions per patient) associated with steroids and cyclophosphamide. The ANCA titer dropped steeply during PE in all cases and was followed by disappearance of systemic symptoms and renal function improvement within four weeks. After a follow-up period of 50 +/- 31.2 months all patients were alive without signs of disease activity; ten had stable renal function, with serum creatinine 1.8 +/- 0.7 mg/dl; two had entered regular dialysis treatment after 44 and 82 months. Our results suggest that the rapid removal of ANCA by means of PE can help control disease activity and reduce the risk of death or end-stage renal disease. PMID- 1521904 TI - Changes in coagulation factors by passage through a dextran sulfate cellulose column during low-density lipoprotein apheresis. AB - To determine the extent of adsorption of coagulation factors by a dextran sulfate cellulose column used for selective removal of low-density lipoprotein (LDL), various coagulation factors were measured before and after application to the column during LDL apheresis. The column almost completely adsorbed many coagulation factors. Although the bradykinin concentration was markedly increased by passing the plasma through the column, this increment was suppressed by nafamostat mesilate which inhibits the initial contact phase of the intrinsic coagulation pathway. The von Willebrand factor, which forms a complex with factor VIII in plasma, is reduced in apheresis with nafamostat mesilate to the same extent as in apheresis without nafamostat mesilate. Thus, coagulation factors seem to be adsorbed by different mechanisms which include activation of the initial contact phase by the negative charges of dextran sulfate and concomitant adsorption with the phospholipid portion of lipoproteins containing apolipoprotein B or with von Willebrand factor. PMID- 1521905 TI - Novel quantitative methods for the determination of biomaterial cytotoxicity. AB - Two novel methods for the determination of biomaterial cytotoxicity using cell culture are presented. The methods combine a standardized protocol for producing extracts from medical devices with either the established MTT assay or a new fluorimetric assay. The suitability of both methods for evaluating the toxicity of candidate materials was demonstrated by resolution of the differences in the toxic effects of serial dilutions of a PVC extract on BHK21 and HT1080 cells. The tests yield highly reproducible, quantitative results and can be applied to materials in the usual physical forms applicable to artificial organs. PMID- 1521906 TI - p53 over-expression is an early event in the development of human squamous-cell carcinoma of the larynx: genetic and prognostic implications. AB - The tumor-suppressor protein p53 is over-expressed in a large fraction of squamous-cell carcinomas of the larynx (LSCCs). p53 overexpression is dependent upon the synthesis of mutated versions of the protein and has been associated with the malignant progression of certain tumor types. In order to examine the prognostic value of p53 immunodetection in LSCCs, we performed a retrospective analysis on a selected series of tumors, using the PAb 1801 and CM1 antibodies. No significant difference in the frequency of p53 over-expression was observed between tumors from patients with early relapse (67%) and those who had been disease-free for more than 5 years (84%). The lack of correlation of p53 immunoreactivity with clinical stage and differentiation grade of LSCCs, together with the coordinated expression of p53 in primary tumors and the corresponding lymph-node metastases, indicate that p53 over-expression is probably unrelated to the biological aggressiveness of these tumors. In addition, the detection of p53 immunostaining in pre-invasive areas as well as in preneoplastic lesions suggests that p53 abnormalities probably constitute a very early event in LSCC development. PMID- 1521908 TI - The study of markers of biological effect in cancer prevention research trials. AB - Biological markers may provide a valuable tool for the development of cancer prevention agents, for monitoring patient compliance to a selected intervention, or for further defining the carcinogenic process. This discussion focuses on markers of biological effect and the rationale for their use in cancer prevention trials. Recent studies with biological markers are investigating their incorporation into phase-I, -II, and -III chemoprevention clinical trial designs. Their use in clinical studies is expected to increase the number of agents that may be evaluated and to provide valuable information on the biological effectiveness of agents, doses, and schedules. Markers may also provide information to help in selecting high-risk groups for prevention research, and to indicate the pathways inhibited and the stage of carcinogenesis affected. Such information may prove of crucial importance in strengthening the rationale for long-term trials and other ancillary research. Biomarker research for colon carcinogenesis is discussed, including examples of a number of recent trials that may influence future progress in this area of prevention research. A crucial step in this process is marker validation as an aspect of major prospective observational and intervention studies where cancer incidence is the endpoint. We cannot be fully confident of markers as intermediate endpoints until the evidence from clinical trials is sufficiently strong to support major public health initiatives for prevention. PMID- 1521907 TI - pS2 protein and steroid hormone receptors in invasive breast carcinomas. AB - We have used immunohistochemical and hormone-binding techniques to determine the presence of estrogen receptors, estrogen-receptor protein, progesterone receptors and pS2 protein in 97 invasive breast cancers. Our group of tumors displayed the same frequency of estrogen receptors and progesterone receptors as other comparable groups, but it contained more tumors containing pS2 protein. We also observed staining of morphologically normal cells in lobules adjacent to the tumors and in several fibroadenomas; both findings vary from some other reports. We attribute these variations to the use of a sensitive immunohistochemical method and choice of the lowest possible threshold to classify a tumor as pS2 positive. If we used a higher threshold, then about 95% of the tumors containing pS2 protein also contained estrogen receptor protein. Our results add further weight to the assertion that tumors containing pS2 protein also display estrogen receptors. The data also provide theoretical and indirect support to the clinical prediction that tumors containing pS2 protein are more likely to respond to hormonal therapy and may have a more indolent course than tumors lacking the molecule. PMID- 1521909 TI - Phenotypic overlaps between pleomorphic malignant T-cell lymphomas and mixed cellularity Hodgkin's disease. AB - Histologically diagnosed, or in part questionable, malignant pleomorphic peripheral T-cell lymphomas (pPTCLs, n = 16) and mixed-cellularity Hodgkin's disease (MCHD, n = 12) were objectively compared by the use of combined immunohistochemistry on paraffin sections, test-point analysis of tissue components, and semi-automated nuclear morphometry on semi-thin resin sections. Classical, qualitative histomorphological distinction of these sub-types of lymphomas proved to be valid and is probably still the best method. Quantitative discriminant features, in order of decreasing significance, were: (i) expression by large atypical cells (LACs) of CD45R0, CD43 and CD45 in pPTCLs, and of CD30 and CD15 in MCHD; (ii) means and standard deviations (SDs) of LAC nuclear-profile areas (greater in MCHD than in pPTCLs); (iii) expression of CD3 by LACs in pPTCLs; (iv) prominence of small lymphoid cells in MCHD; (v) higher percentage of medium-sized lymphoid cells in pPTCLs; and (vi) higher SDs of nuclear-profile circularity factor of small lymphoid cells in MCHD. The medians of the largest nucleolar profile areas in LACs per field did not differ in pPTCLs and MCHD, but dispersion of individual values towards higher levels was significantly greater in the latter. Stepwise discriminant analysis of test point and nucleometric variables that best distinguished pPTCLs from MCHD revealed considerable overlaps, and questionable cases tended to be intermediate between the two. In conclusion, our results confirm and expand the notion of intra-group heterogeneity, with indistinct borders and the existence of intermediate phenotypes between these two taxonomic categories of malignant lymphomas. PMID- 1521910 TI - Determination of placental ferritin (PLF)-positive lymphocytes in women in early stages of breast cancer. AB - Previous studies have proved that a certain acidic isoform of ferritin is specifically synthesized by the placenta and breast-cancer tissue. In this context it has been further reported that the determination of this so-called placental isoferritin (PLF) on the surface of a subset of peripheral lymphocytes is highly specific and sensitive for early stage breast cancer. By use of the monoclonal antibody CM-H-9 and flow cytometry, the levels of placental ferritin (PLF)-positive cells were determined in 133 female patients undergoing surgical excision of a controversial or highly suspicious lesion of the breast detected by mammography. In addition, 61 healthy blood donors served as controls. Values of PLF-positive cells in breast cancer patients differed significantly from those found in women with benign diseases and healthy controls (3.87% vs. 1.55% and 2.02, respectively; p less than 0.00001). Analysis of prognostic factors in breast cancer patients (tumor size, lymph-node status, menopausal status, estrogen receptor status, histologic grading and grading subfactors) revealed significantly higher levels of PLF-positive cells in lymph-node-negative patients compared with node-positive patients (p less than 0.00001). Furthermore, levels of PLF-positive cells showed a significantly negative correlation with tumor size and nuclear polymorphism. In 15 patients who underwent a guide-wire-directed surgical biopsy for a non-palpable, mammographically suspect lesion, 4 cases of cancer correlated with high values of PLF-positive lymphocytes while only 1 patient with a benign histologic result exhibited more than 4% positive cells. PMID- 1521911 TI - Matrigel promotes retinoblastoma cell growth in vitro and in vivo. AB - Cells derived from retinoblastomas grow slowly in vitro and only very rarely form tumors in nude mice. Matrigel, a mixture of components normally found in basement membranes, promotes the growth of Y-79 and WERI-Rb1 retinoblastoma (Rb) cells when added to suspension cultures of the 2 Rb cell lines. It also substantially increases cell adhesion in vitro. Y-79 cells, seeded into a Matrigel matrix, form round colonies over a 3-week period similar to those of control, weakly metastatic murine melanoma cells. In vivo, s.c. co-injection of Matrigel with either Y-79 or WERI-Rb 1 cells into nude mice promotes retinoblastoma tumor formation. Transplantation of as few as 1,000 cells allows for xenografting under these conditions, while no tumors were observed in the absence of Matrigel, even at 10 x 10(6) cells/inoculum. The tumors produced have the expected morphology and express an mRNA for a highly specific retina/retinoblastoma marker protein, the interphotoreceptor retinoid-binding protein. Thus, the xenografts obtained maintain the original morphological and molecular characteristics of the injected cells and represent a useful model for in vivo studies of retinoblastoma growth and treatment. PMID- 1521913 TI - Biodistribution of lymphokine-activated killer (LAK) cells in Wag rats after hepatic-artery or jugular-vein infusion. AB - This study deals with the biodistribution of syngeneic radiolabeled lymphokine activated killer (LAK) cells in Wag rats after infusion via the hepatic artery or the jugular vein. The biodistribution of 111Indium-labeled LAK cells was evaluated using serial whole-body gamma camera imaging. Furthermore, we investigated 2 factors that might influence the biodistribution of these effector cells: purity of LAK cells and administration of interleukin-2 (IL-2). After injection of 111Indium-labeled LAK cells via the hepatic artery or via the jugular vein we could detect important differences in the biodistribution pattern up to 5 hr after injection. LAK cells administered via the jugular vein were all found in the lungs up to 2 hr after injection and then redistributed to the liver and to the spleen. LAK cells administered via the hepatic artery were all found in the liver after injection and redistributed after 2 hr mainly to the spleen. About 8 hr after injection we could no longer detect any differences in the biodistribution pattern according to the route of administration. Biodistribution was followed for up to 72 hr after injection but the pattern showed no change after 8 hr, whichever the route of administration. A purified adherent-LAK population, a large granular lymphocyte culture with only 6% T cells, showed the same distribution pattern as standard LAK cells (40% T cells). Infusions of 40,000 units of IL-2 per day, starting 3 days before and continuing after administration of radio-labeled LAK cells, accelerated the redistribution of these cells by both routes of administration. We conclude that up to 2 hr after local infusion, a high concentration of LAK cells in the first capillary bed can be obtained. Therefore, local administration of LAK cells may be more effective against tumors. PMID- 1521912 TI - Influence of recombinant human interleukin (IL)-7 on disease progression in mice infected with Friend virus complex. AB - Recombinant human (rhu) IL-7 was evaluated for its influence on disease progression in mice infected with the polycythemia-inducing strain of the Friend virus complex (FVC). DBA/2 mice were injected i.v. with FVC, and then treated s.c. with rhuIL-7. IL-7 significantly prolonged survival time and decreased spleen focus-forming virus (SFFV) levels, expression of SFFV mRNA and SFFV protein production in FVC-infected mice. IL-7 did not appear to directly inactivate SFFV. Although both splenic weight and cellularity in FVC-infected mice treated with IL-7 were higher than those of normal mice, they were respectively 58% and 66% lower than those of the untreated FVC-infected mice. NK cell activity was substantially lower in FVC-infected mice than in normal mice, while IL-7 restored NK-cell activity to normal levels. IL-6 and IFN-gamma levels were markedly reduced in FVC-infected mice compared to normal mice, but treatment of FVC-infected mice with IL-7 restored these cytokine levels. While the actual mechanisms of these effects are not yet known, the results suggest the potential therapeutic efficacy of IL-7 for certain hematopoietic and viral disorders, possibly mediated through an action on accessory cells and cytokine production. PMID- 1521914 TI - Influence of glucose on metabolism and growth of rat glioma cells (C6) in multicellular spheroid culture. AB - The metabolism and growth of rat glioma C6 cells in multicellular spheroid culture depended strongly on the glucose supply. A low glucose level (0.1 g/l) in the culture medium reduced lactate production, increased oxygen consumption and diminished hydrogen ion production under normoxia as well as hypoxia. A high glucose level (10 g/l glucose) increased lactate production, had no significant influence on oxygen consumption and increased the hydrogen ion production under hypoxia. Hydrogen ion release from cells under normoxic and hypoxic conditions could be significantly diminished by amiloride (l mM), indicating the involvement of the Na+/H+ exchanger. The growth of the C6 spheroids was enhanced under low glucose conditions, possibly due to the more physiological extracellular pH in the deeper regions of the spheroids. The growth was inhibited under high glucose conditions, which seemed to be toxic due to a massive hydrogen production giving acidosis. The glucose supply strongly influenced the local hydrogen ion production inside the C6 spheroids and this might in turn lead to changes in the response to different therapeutic modalities. PMID- 1521915 TI - Effects of short-chain fatty acids on growth and differentiation of the human colon-cancer cell line HT29. AB - Short-chain fatty acids (SCFAs), namely butyrate, acetate and propionate, originate from the bacterial fermentation of dietary fibers and are the predominant anions present in the large bowel. Our study was carried out to investigate the effects of SCFAs on growth of the human adenocarcinoma cell line, HT29. The results show that, under our culture conditions, both propionate and butyrate inhibit growth of HT29 cells, whereas acetate has no significant effect. The antiproliferative effect of propionate or butyrate is associated with an inhibition of FCS-induced activation of ornithine decarboxylase (ODC), a key enzyme of polyamine metabolism. Inhibition of growth induced by either propionate or butyrate is not reversed by the addition of putrescine, which reveals that these SCFAs are not acting solely on the ODC/polyamine system. Our data show that propionate and butyrate, unlike acetate, induce an increase in alkaline phosphatase activity, which reflects a more differentiated phenotype than that of untreated control cells. Taken together, our results suggest that propionate, like butyrate, may play an important role in the physiology of the colon and could partially account for the protective effect of dietary fibers with respect to colon carcinogenesis. PMID- 1521916 TI - Derivation of tumorigenic and non-tumorigenic mouse alveolar type-II cell lines from fetal type-II cells after a combined in vivo/in vitro carcinogen treatment. AB - Alveolar type-II cells were isolated from the lungs of fetuses (day 18 of gestation) of the A/WySnAf (A/Sn) mouse strain, which were treated in utero at day 15 with the directly-acting carcinogen N-ethyl-N-nitrosourea (ENU). The isolated type-II cells were again treated with ENU during their initial growth in vitro. After a prolonged culture period, 5 cell lines were obtained, which were identified as type-II cell lines. Differences between cell lines were found with respect to contact-inhibited growth, cell doubling time and ability to grow in a serum-free medium. Two out of the 5 cell lines produced highly invasive type-II cell carcinomas after s.c. injection of 5 x 10(6) cells into nude mice. Thus, both tumorigenic and non-tumorigenic mouse alveolar type-II cell lines were derived after this combined in vivo and in vitro carcinogen treatment of fetal mouse alveolar type-II cells. This offers the possibility of studying in vitro the factors thought to influence lung tumorigenesis in vivo. In addition, our findings strongly suggest that alveolar type-II cells are the progenitor cells of malignant mouse lung tumors. PMID- 1521917 TI - Effects of areca nut on growth, differentiation and formation of DNA damage in cultured human buccal epithelial cells. AB - Because the high incidence of oral cancers in South-East Asia is causally linked to the common habit of betel quid chewing, the effects of an aqueous extract of areca nut, one of the main ingredients of the quid, on growth, differentiation, morphology and DNA damage were studied in cultured human buccal epithelial cells. An acute exposure (3 hr) of the cells to the extract altered their morphology and induced ridges in the plasma membrane, with indications of internalization of extract particles. Such exposure also caused formation of DNA single-strand breaks which accumulated during post-treatment culture, indicating continuous exposure to residual particles and/or the possibility of inhibited DNA repair. The extract accelerated terminal differentiation of the cells, measured as involucrin expression at relatively non-toxic levels. The extract caused similar loss of colony-forming efficiency in normal cells and in a buccal carcinoma cell line (SqCC/YI) which was defective in its ability to undergo differentiation, indicating that extract toxicity could occur independently from this response. Finally, the genotoxicity of the salivary areca-nut-specific carcinogen 3-(N nitrosomethyl-amino)propionaldehyde, was demonstrated by the formation of DNA protein cross-links and DNA single-strand breaks in normal buccal epithelial cells. These findings in vitro suggest that betel quid carcinogenesis in the human oral cavity may involve cytopathic alterations of normal cell morphology, growth and differentiation, as well as formation of DNA damage by areca-nut related agents extracted or formed in saliva. PMID- 1521918 TI - Transforming activity and the level of Tax protein: effect of one point mutation in HTLV-I tax gene. AB - The transcriptional trans-activator molecule of HTLV-I, Tax, is known to transform rodent fibroblasts. A revertant clone expressing Tax was obtained by treating transformed Rat-I cells harboring a single copy of the tax gene with a mutagen. Sequence analysis of the tax gene of the revertant clone revealed that it had one point mutation at codon 12(CTT----TTT), resulting in a change from Leu to Phe. The colony-forming efficiencies of the cells transfected with the mutant tax gene (mu71 tax) were significantly lower than those transfected with the wild type by the soft-agar method. This difference was shown to be due to the instability of mu71 Tax. PMID- 1521920 TI - Effects of experimental conditions on the production of interleukin-1 alpha and 1 beta by human endothelial cells cultured in vitro. AB - We have characterized the production of IL-1 alpha and -beta in primary and passaged cultures of quiescent human umbilical vein endothelial cells (HUVECs) using highly specific and sensitive solid-phase enzyme immunoassays. Primary cultures produced both immunoreactive IL-1 alpha and IL-1 beta following stimulation with lipopolysaccharide with the alpha form predominating over the beta. Most of the IL-1 produced remained cell-associated. Primary, but not passaged, cultures were significantly contaminated by macrophage-like cells, possibly accounting for higher production of IL-1, especially IL-1 beta. Gel filtration of secreted proteins derived from cultured HUVECs showed that the immunoreactive IL-1 alpha exhibited the expected molecular weight (17 kDa), but cell-associated IL-1s appeared to be a mixture of the 17 kDa protein and of higher molecular weight precursors. Mitogens in the culture medium (serum and endothelial cell growth supplement) were powerful stimuli of endothelial IL-1 production and accounted for the relatively high basal IL-1 levels observed in the cultured endothelial cells. The proliferative phenotype of the endothelium is possibly linked to the expression of high level of IL-1, which until now was thought to be an autocrine inhibitor of endothelial cell mitosis. PMID- 1521919 TI - The H-ras oncogene regulates expression of 70- and 45-kDa cell-surface molecules whose expression correlates with tumor-cell immunogenicity. AB - The effects of the H-ras oncogene on fibroblast cell tumorigenicity and immunogenicity was studied in transfectants of the BALB/c 3T3 clone A31 fibroblastoid cell-line. Cells that were transfected with MC29-LTR-H-ras (98/6) or MC29-LTR-v-myc + H-ras (98/4v) and were inoculated into syngeneic BALB/c mice were tumorigenic in 100% and 60% of animals respectively. By contrast, transfectants containing the pSV2neo plasmid alone (98/1) displayed normal characteristics both in vitro and in vivo. Inoculation of mice with mitomycin-C treated 98/1 or 98/4v cells induced an effective protective immunity to a challenge of live 98/4v cells, and a partial immunity against 98/6 cells. Mitomycin-C-treated 98/6 cells failed to render immunity against a challenge of either 98/6 or 98/4v cells. To correlate immunogenicity and tumorigenicity of the different cell types with cell-surface-antigen expression, we prepared MAbs against 98/4v cells in syngeneic mice. Immunohistochemical and immunoblot analysis revealed that MAbs 102 and 104 recognized 2 protein band of 70 and 45 kDa respectively, which were expressed predominantly in 98/1 and 98/4v cells. A third immunoreactive protein band of 44 kDa that reacted with MAb 6 was expressed at a similar cell-surface density on all cell types. Cell-differentiation inducing agents, such as DMSO, retinoic acid or sodium butyrate, were all found to induce 98/6 cell flattening and morphological changes toward a normal phenotype that were followed by up-regulation of the 70- and 45-kDa antigens. The results suggest that regulation of expression of the 70- and 45-kDa molecules is affected by H-ras, and that expression of these cell-surface molecules may be relevant to tumor cell immunogenicity. PMID- 1521921 TI - Enhanced induction of lymphokine-activated killer activity after lentinan administration in patients with gastric carcinoma. AB - In 15 patients with gastric carcinoma, peripheral blood mononuclear cells (PBM) were obtained serially before and 3, 5 and 7 days after lentinan administration. The generation of lymphokine-activated killer (LAK) activity, induced by in vitro activation of PBM with interleukin 2 (IL 2), was significantly augmented 5 days after a single intravenous dose of 2 mg lentinan, when compared with that before lentinan injection. Natural killer (NK) activity of PBM was also significantly enhanced 7 days after the drug injection. However, the distribution of lymphocyte subsets exhibited no significant change following lentinan administration. PMID- 1521922 TI - Aromatase inhibitors regenerate the thymus in aging male rats. AB - The thymus can be regenerated in aging rats by surgical or chemical castration and regeneration is inhibited by testosterone, which may exert this effect, at least in part, through its conversion to estradiol. An attempt has been made to regenerate the thymus in intact aging rats using inhibitors of the aromatase system, in the hope that this maneuver could lead to the use of such chemical intervention in the treatment of immunodeficiency syndromes. Young adult and aging (18-month-old) male rats were orchidectomized under ether anesthesia and 7 days later given s.c. implants of testosterone in silicone elastomer (SILASTIC) tubing. Some rats received testosterone together with a five-fold excess of the aromatase inhibitor 1,4,6-androstatriene-3,17-dione (ATD). One group of young intact rats received implants containing 25 mg ATD and a group of 18-month-old intact rats received 125 mg ATD or 25 mg of another, more powerful aromatase inhibitor 4-hydroxyandrostenedione (4-OH). On the 28th day after implanting, rats were killed and the thymus, spleen, prostate gland and seminal vesicles removed for weighing and histology. In addition, estrogen receptors were measured in the thymus. The thymus was enlarged after orchidectomy and greatly restored in aging rats. In aging rats, both aromatase inhibitors restored the thymus, which appeared normal histologically. In addition, ATD enlarged the thymus in young intact animals. Doses of testosterone which restored the accessory sex organs to weights measured in intact rats prevented the effects of orchidectomy on the thymus, and in old rats the effects of testosterone were blocked by ATD in both thymus and spleen. Available cytosolic estrogen receptors were reduced in thymus of testosterone-treated orchidectomized rats, and this effect blocked by ATD, which itself was apparently able to induce estrogen receptors. Receptors could not be detected in thymus from aging rats, but were measureable in cytosols from thymus of orchidectomized or ATD-treated old rats. It is therefore possible to restore the thymus in intact aging rats without recourse to surgical or chemical castration, and such a maneuver may possibly be of use to enhance an immune system weakened by aging or disease. PMID- 1521923 TI - Methyl inosine monophosphate: a potential immunotherapeutic for early human immunodeficiency virus (HIV) infection. AB - MIMP is a new thymomimetic purine under development for immunorestorative therapy. Lymphocytes were obtained from eight patients with acquired immunodeficiency disease (AIDS), eight with symptomatic pre-AIDS (ARC), and 22 normal controls and were stimulated in vitro with phytohemagglutinin (PHA). AIDS patients (mean CD4 counts of 40) showed PHA responses less than 10% of control while ARC patients (mean CD4 counts of 544) showed responses approximately 50% of the control responses. MIMP (0.1, 1, 10 and 100 micrograms/ml) progressively augmented the PHA responses in all these groups. The augmentation of the responses of the leukocytes of AIDS patients while statistically significant was minimal. The augmentation of the responses of ARC patients was significant and their maximal responses approached control levels. The effect of 1 micrograms/ml MIMP was comparable with that observed with indomethacin (10(-6) M) and interleukin-2 (IL2 - 4 units/ml) and was additive with each of these stimulants. In a parallel manner, MIMP restored the suppression of control lymphocytes induced by the immunosuppressive 17 amino acid fragment of the P41 peptide of HIV. In vivo experiments showed that MIMP significantly delayed death in a murine FLV AIDS model at a dose of 1 mg/kg by the oral or parenteral route. MIMP is under preclinical development for early HIV disease to forestall progression to AIDS by attenuating virus-induced immunosuppression. PMID- 1521924 TI - Interleukin-6 (IL-6) in adjuvant arthritis of rats and its pharmacological modulation. AB - The levels of serum interleukin-6 (IL-6) were measured during the course of adjuvant arthritis (FAA) in male Lewis rats. In the course of the disease serum IL-6 levels increase with a clear correlation with morphologic disease signs. Additionally, the FAA-inducing antigen, heat-killed Mycobacterium tuberculosis, was found to be a strong inducer of IL-6 production by spleen cells in vitro. The effects of the anti-rheumatic drugs indometacin, dexamethasone, cyclophosphamide and cyclosporin A (CsA) on IL-6 levels during FAA were determined. Complete normalization of serum IL-6 levels was observed with dexamethasone, cyclophosphamide and CsA whereas indometacin only partly reduced serum IL-6 levels. PMID- 1521925 TI - Potentiation of HIV envelope glycoprotein and other immunogens by endotoxin (ET) and its molecular fragments. AB - The structural requirements for the immunopotentiating (adjuvant) effect of endotoxin (ET) were investigated. Mild hydrolysis (0.2 N acetic acid at 95 degrees C) was applied to various ET preparations and the lipid rich (Lipid A) and polysaccharide-rich (PS) preparations obtained were tested as adjuvants on three immunogens: sheep red blood cells (SRBC), L-glutamine: L-lysine: L-alanine containing random synthetic polypeptide (GLA-40), and recombinant HIV viral envelope polypeptide (CBre3). It was found that not only the Lipid A precipitates, but under certain hydrolytic conditions the non-toxic PS preparations were also potent adjuvants. The exact conditions of hydrolysis which led to the isolation of immune adjuvant bacterial products were established. These materials were also tested for endotoxicity (Limulus lysate clotting, chick embryo lethality and local Shwartzman skin reactivity), as well as for TNF generating activities. It was found that TNF generation runs parallel with toxicity of the samples, but it does not follow the adjuvant activity of the isolates. Chemical analysis of the preparations indicated that they did not contain residual ET or Lipid A, however, they did not exclude that deacylated and dephosphorylated skeletal remains of ET are among those components in these preparations which have immunomodulatory activity. PMID- 1521926 TI - Tunicamycin inhibits function and expression of the high-affinity IL-2 receptor in a murine IL-2-dependent cell line. AB - Murine interleukin-2-dependent T-lymphocytes (CT6) were treated with tunicamycin, an inhibitor of both glycoprotein and ganglioside synthesis, to study the involvement of glycosylation in the IL-2 proliferative response. Tunicamycin inhibited proliferation in a dose-dependent manner at concentrations which did not inhibit protein synthesis (10-50 ng/ml). Swainsonine, a glycoprotein processing inhibitor, had no effect on proliferation. Inhibition of proliferation by tunicamycin was accompanied by an inhibition of binding of 125I-IL-2 to its high-affinity receptor. Scatchard analysis showed that receptor number was decreased by tunicamycin treatment. On the other hand, tunicamycin did not affect either the binding of the monoclonal antibody 7D4, specific for the 55 kDa low affinity protein subunit of the IL-2 receptor, or the recycling of the IL-2 receptor. To determine the specific effects of tunicamycin on the biosynthesis of particular CT6 glycoconjugates, cells were radiolabeled with 3H-glucosamine and incorporation into ganglioside, neutral glycolipid and glycoprotein fractions was measured. Low doses of tunicamycin inhibited ganglioside synthesis and glycoprotein glycosylation to the same extent, whereas no effect on neutral glycolipid synthesis was observed. These results suggest that glycosylation of glycoprotein and/or gangliosides might play an important role in the formation of a functional high-affinity IL-2 receptor complex in CT6 cells. PMID- 1521927 TI - The synergistic immunosuppressive potential of cyclosporin metabolite combinations. AB - Out of the 29 cyclosporin (CS) metabolites defined so far seven representatives were isolated from the bile of liver grafted patients, purified by HPLC and characterized by FAB-MS and/or 1H-NMR. These were used to determine the growth inhibitory effects on concanavalin A stimulated rat lymphocytes (LN). Metabolites diluted in culture medium at concentrations re-checked by HPLC at the respective assay time were added and proliferation determined by [3H]-thymidine incorporation after 48 h. A 50% growth inhibition of LN by single metabolites (AM) was achieved at the following concentrations (mg/l): CS: 0.023; primary metabolites AM1: 0.11; AM1c: 0.65; AM9: 1.05; secondary metabolites AM19: 1.02; AM4N9: 1.02; H355: 1.85; AM1A: 4.5. Although all metabolites were immunosuppressive at higher concentrations in vitro on a single metabolite level, only AM1 with 20% of the activity of native CS seemed to play a role in vivo. However, when we tested the antiproliferative effects of double or triple metabolite combinations, we found a strong synergism not only of primary metabolites, but even with combinations including secondary metabolites. The concentration of the participating metabolites necessary to decrease LN growth by 50% was far below the trough levels observed in vivo. Finally, to mimic to some extent the in vivo situation we determined the interaction of native CS with single metabolites or double combinations. In contrast to the clear synergism in the absence of CS the combinations of metabolites with native CS resulted in an additive growth inhibition. These results indicate an immunosuppressive potential of all metabolites tested and a clear synergism of metabolites in the absence of CS. Although up to double metabolite combinations did only additively enhance CS induced immunosuppression, the combination of 29 metabolites occurring in vivo might have significant immunosuppressive effects in situations where CS levels drop below active concentrations. PMID- 1521928 TI - Immunomodulating properties of carbamazepine in mice. AB - The protective effects of carbamazepine (CBZ) were studied in mice inoculated with Lewis Lung Carcinoma (3LL), Madison Lung Carcinoma (M109), L5178Y lymphoma, L1210 leukaemia and Candida albicans. There was no significant increase in survival time of mice treated with CBZ. However, CBZ, as well as its metabolite CBZ 10-11 epoxide (CBZ 10-11 EPOX), showed a significant increase in NK-cell activity. CBZ also produced a significant increase of phagocytosis and killing properties of PMNs. There was no significant difference in the stimulation of splenic lymphocyte blastogenesis by different concentrations of phytohaemagglutinina (PHA), observed between the controls and CBZ treated mice. The results demonstrate that the effect of chronic treatment with CBZ on the immune response is a complex phenomenon which remains a challenge for future research. PMID- 1521929 TI - The immunomodulator AS101 administered orally as a chemoprotective and radioprotective agent. AB - AS101 [ammonium-trichloro (0,0' dioxyethylene)tellurate] is a new immunomodulator shown previously to stimulate the production of various cytokines in vitro and in vivo, and to have minimal toxicity. In the present study we explore the possibility of oral administration of AS101 to mice via cannulation in lieu of interperitoneal or intravenous administration reported to date. Our studies show that oral administration of AS101 at a dose ranging between 50 and 100 micrograms/mouse promotes hemopoietic regeneration after treatment with sublethal doses of cyclophosphamide (CYP) and protects mice from the lethal effects of this compound. In addition, AS101 administered orally confers a strong radioprotective effect upon mice when given before irradiation. PMID- 1521930 TI - The interleukins-1 alpha, -1 beta, and -2 do not acutely disrupt the murine blood brain barrier. AB - Previous studies have suggested that some of the central nervous system (CNS) effects of interleukin-2 (IL-2) and perhaps other cytokines might be mediated through disruption of the blood-brain barrier (BBB). We investigated the ability of human IL-2 and, in selected studies, human IL-1 alpha and human IL-1 beta to disrupt the BBB to radioiodinated bovine serum albumin (RISA) after intravenous (i.v.) and intracerebroventricular (i.c.v.) injection. No disruption of the BBB occurred for up to 2 h after the i.v. injection of 2 micrograms/mouse of IL-2 (10(5) U/kg of body weight), 2 micrograms of IL-1 alpha (10(7) U/kg), or 2 micrograms of IL-1 beta (10(7) U/kg). This dose of i.v. IL-2 also did not affect BBB permeability to RISA in the brain to blood direction. Damage to the BBB induced by hypertension elicited by i.v. epinephrine was not enhanced or prolonged by IL-2. When given directly into the CNS by the i.c.v. route, 100 ng of IL-2 (2.2 x 10(5) U/kg of brain), 100 ng of IL-1 alpha (2.2 x 10(7) U/kg of brain), or 100 ng of IL-1 beta (2.2 x 10(7) U/kg of brain) had no effect on BBB integrity in either the blood to brain or the brain to blood direction. We conclude that the effects of IL-1 alpha, IL-1 beta, and IL-2 on the CNS, as studied under these conditions, are not due to disruption of the BBB but are mediated by other mechanisms including the ability of some interleukins to cross the BBB by a saturable transport system described previously. PMID- 1521931 TI - Hydrolysis and association of leucine enkephalin to lymphomic and erythroleukaemic cell lines--II. AB - The relationship between the hydrolysis of labelled leucine enkephalin and the association of its radioactive label to the cells of lymphomic and erythroleukaemic cell lines have been studied using intact cells and resealed membranes obtained from these cells as models. Hydrolysis by cell enzymes and its effect on association have been analysed using protease inhibitors and non hydrolysable enkephalin analogues. Results obtained confirm that hydrolysis of the pentapeptide is a prerequisite for association of the radiolabel to cells. The same results provide evidence of marked differences between enkephalin hydrolysis by whole cells and hydrolysis measured in the presence of resealed membranes, suggesting the existence in intact cells of proteolytic enzymes other than those bound to the membranes. The lack of reversibility of association and the intracellular localization of the radioactive label suggest that the association measured is prevailingly caused by internalization of a hydrolysis fragment, and not by binding to receptors. In order to determine the nature of the active fragment, association was measured in the presence of all four labelled N-terminal hydrolysis fragments of leu-enkephalin under conditions of nearly-total inhibition of proteolytic enzymes. Under these conditions, the label carried by Tyr, but not that carried by the other N-terminal fragments, was associated with cells. Free Tyr, furthermore, inhibits the association to cells of both labelled Tyr and leu-enkephalin. Data summarized above are consistent with the hypothesis that the radioactive label is taken up by the cells as Tyr, freed from the parent peptide by cell-related enzymes. The same data tend to exclude that a relevant fraction of the intact pentapeptide is bound to membrane receptors or that the radioactive label is carried into the cell by a N-terminal fragment other than Tyr. PMID- 1521932 TI - Modulation of colony-stimulating activity by interleukin 1 in mice: opposing effects of combined treatment with indomethacin or prostaglandin E2. AB - Following previous observations that interleukin 1 (IL-1) may have both positive and negative effects on the levels of circulating colony-stimulating factors (CSF) in mice, we have investigated the impact of human rIL-1 beta administration on serum concentrations of colony-stimulating activity (CSA, as defined by biossay) and macrophage-specific colony-stimulating factor (CSF-1, measured by RIA). In addition, we have studied the effects of IL-1 administered in conjunction with indomethacin or prostaglandin (PG) E2. Besides confirming the finding that exogenous IL-1 leads to a rapid increase in CSF detection, we obtained evidence that IL-1 may also result in the production of cyclo-oxygenase pathway products that down-regulate the IL-1-induced burst in CSA and CSF-1 levels. While co-treatment of mice with indomethacin led to a further increase in CSF detection, the combined exposure to IL-1 and PGE2 resulted in a significant impairment of the stimulatory activity of IL-1. PMID- 1521933 TI - Thymic serum activity inhibitors study. PMID- 1521934 TI - Drug-specific immune responses induced by procainamide, hydralazine and isoniazid in guinea-pigs. AB - The drug-induced graft vs host reaction (GVHR) hypothesis requires, as its first step, specific T-cell immune responses to the drug-modified self. Procainamide, isoniazid and hydralazine are known to provoke various allergic reactions including GVHR-like adverse effects in man. We now report that drug-specific immune responses can easily be induced by these drugs in guinea-pigs. Twenty-five milligrams of each of these drugs and penicillin G, which is known to make covalent bonds with proteins and to also induce drug-specific immune responses, were mixed with complete Freund's adjuvant (CFA) and subcutaneously (s.c.) injected twice at an interval of 2 weeks into female Hartley guinea-pigs. The antibodies to these drugs were assessed by means of an enzyme-linked immunosorbent assay (ELISA). Two weeks after the last injection, all animals treated with isoniazid, hydralazine and penicillin G produced high titers of antibodies to these drugs. Antibodies to procainamide were also detected, although their antibody titers were low. The specificity of the antibodies produced were tested by the inhibition of ELISA and concentration-dependent inhibition was observed. Delayed type hypersensitivity (DTH) reactions were also observed in the animals treated with procainamide, isoniazid and hydralazine 2 weeks after the last injection. These results suggest that the allergic reactions observed in clinical use are related to the inducing potential of drug-specific immune responses in an animal system. Therefore, immunization of guinea-pigs with test drugs and CFA may give useful information for predicting the occurrence of allergic reactions in man. PMID- 1521935 TI - Popliteal lymph node enlargement induced by procainamide. AB - The ability of procainamide (PA) to induce primary local popliteal lymph node (PLN) reactions has been investigated. We employed an in vitro drug-metabolizing system, based on the hypothesis that the negative result for PA in a PLN assay (PLNA) was due to insufficient metabolizing activity at the reaction site. PA was incubated previously in vitro with the S-9 mixture derived from rat liver. The reactants were ultrafiltered in order to eliminate high molecular-weight molecules, and then the low molecular-weight fraction was subcutaneously (s.c.) injected into the hind footpad of mice. PLN reactions were assessed by weighing the popliteal lymph node of the injected side. The reactants of more than 5 mg of PA and S-9 mixture induced PLN enlargement in C3H/He mice 8 days after injection. BALB/c and C57BL/6 mice were also susceptible to PLN reaction in response to the reactants of PA (10 mg) and S-9 mixture. PLN reactions to PA were induced 2 days after the injection and sustained until 18 days. Contact of PA with the S-9 mixture for 30 min at 37 degrees C was sufficient to induce PLN enlargement. However, contact for 24 h reduced the peak reaction. On the other hand, PA which had not been incubated with the S-9 mixture and acetylprocainamide (acetylPA) gave little or no reaction. Local PNA has not been considered to be suitable for the detection of drugs with the potential to induce immune disorders in cases where a metabolite contributes to the adverse reaction. However, the employment of an in vitro drug-metabolizing system may overcome that defect. PMID- 1521936 TI - The role of lymphocyte production and migration in the lymphopenia caused by 2 acetyl-4-tetrahydroxybutyl imidazole. AB - 2-Acetyl-4-tetrahydroxybutyl imidazole (THI), a component of the food colouring ammonia caramel, has been shown to produce a profound and rapid lymphopenia in peripheral blood in the rat. In order to investigate whether the cause of the lymphopenia was due to the reduced production and influx in the circulation, redistribution of lymphocytes into other lymphoid compartments or an increased cell death, THI (1 mg/kg/day) was given in the drinking water for up to 14 days to F344 rats. A profound depletion of lymphocytes after already 1 day was only found in the blood compartment, whereas no such marked and rapid changes were found in the cellularity of other lymphoid compartments. The proportion and absolute number of DNA-synthesizing cells in each lymphoid organ was quantified using an antibody directed against incorporated 5-bromo-2'-deoxyuridine (BrdU), 1 h after a single BrdU injection. Additionally, enumeration and localization of BrdU+ cells was determined at later time points after a single BrdU injection by flow cytometry and immunocytochemistry, in order to examine the distribution and localization of recently formed (BrdU+) lymphocytes. THI treatment had no effect on the proliferation rate and the distribution of newly formed (BrdU+) cells in the lymphoid organs. However, migration studies revealed that THI treatment resulted in an increased percentage of fluorescein-labelled peripheral blood lymphocytes found in the spleen and bone marrow and a decreased percentage in the cervical and mesenteric lymph nodes, 24 h after injection. Collectively these results indicate that the lymphopenia in the peripheral blood compartment after THI treatment, is caused by a rapid sequestration of lymphocytes into the spleen and bone marrow rather than by a reduced lymphocyte production and release into the periphery. The fact that THI also caused lymphopenia in splenectomized rats, indicates that the spleen does not play an active part in the change in migrational behaviour of lymphocytes after THI treatment. Finally, as there was no increase in the absolute number of lymphocytes found in the spleen or bone marrow it seems they are rapidly degraded. PMID- 1521937 TI - 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) inhibits the activation of antigen specific T-cells in mice. AB - There are conflicting data in the literature regarding target cells in 2,3,7,8 tetrachlorodibenzo-p-dioxin (TCDD)-induced immunotoxicity. In the present study, adult male C57BL/6 mice were exposed to TCDD (50 micrograms/kg) 4 days prior to immunization with ovalbumin (OVA). The effect of TCDD on the specific immune response in vivo was determined by T-cell proliferation and IL-2 production in response to either OVA or anti-mouse-CD3 antibodies plus PMA in vitro. The antigen-specific T-cell proliferation and IL-2 production in response to OVA were significantly suppressed by TCDD, while the polyclonal response to anti-CD3 antibodies plus PMA was not affected. This indicates that even at a high dose of TCDD the intra T-cell signalling pathways in resting cells are not disturbed, but TCDD selectively impairs the antigen-specific activation of T-cells. Since activated T-cells are required in antibody responses to T-dependent antigens, the low number of such cells observed in the present study, may well explain the suppressive effects of TCDD on humoral immunity reported previously. PMID- 1521938 TI - Mechanism of ethanol-mediated immunosuppression in mice: ethanol suppresses T cell proliferation without affecting IL2 production and IL2 receptor expression. AB - The effect of extended ethanol consumption in young C57BL/6 mice on T-cell proliferation was studied. Splenic cells of young mice (3-4 months old), fed with one of three different liquid diets (5% ethanol, maltose-substitute, or standard liquid diet) for 28-38 days were cultured with plant lectins to assess T-cell proliferation and IL2 production. Expression of T-cell subset markers (CD4+/CD8+) was also determined. Then, Con A-activated T blast cells were assessed for their ability to express IL2 receptor (IL2R) and to respond to IL2. Finally, the proliferative response of splenic cells to PMA/ionomycin was assessed. The results showed that both lectin- and PMA/ionomycin-induced mitogenesis and IL2 dependent proliferation of T-cells from ethanol diet-fed mice were diminished as compared with that of maltose-substitute diet or standard liquid diet. However, the ability of T-cells from ethanol diet-fed mice to produce IL2 and to express IL2 R or CD4+/CD8+ subset markers was not affected. Furthermore, the magnitude of ethanol-mediated suppression of T-cell proliferation induced by PMA/ionomycin was comparable with that induced by Con A. These results taken together indicate that ethanol suppresses T-cell proliferation by interfering with events following the IL2-IL2R interaction. Therefore, it is likely that ethanol inhibits murine T-cell proliferation by selectively affecting the progression (IL2R-mediated events) rather than the initiation (mitogenic receptor-mediated events) of the cell cycle. PMID- 1521939 TI - Changes in plasma lipoprotein levels during a hiking expedition in South America. AB - Eleven males participated in a hiking expedition over a period of 6 weeks during which they walked an average of 15 km per day, resting days included. The participants completed a seven-day estimated dietary record before and during the expedition. Their habitual dietary intake before the expedition was typical of a Western diet. During the expedition most animal products, with the exception of canned fish, were excluded from the diet. The dietary intake of fat and carbohydrate changed from 36.9% and 40.6% to 14.0% and 76.4% respectively. Cholesterol intake dropped from 557 mg to 92 mg. Mean plasma total cholesterol (TC) decreased from 190.9 mg/100 ml to 142.0 mg/100 ml. These changes were mainly due to changes in low density lipoprotein cholesterol (LDL-C). Although high density lipoprotein cholesterol (HDL-C) did not change, the ratio of HDL-C to TC increased significantly. It can be concluded that drastic dietary changes, together with increased physical activity and weight loss resulted in major plasma lipoprotein changes. The expected fall in HDL-C due to a high carbohydrate diet was counteracted by the increased physical activity and weight loss. PMID- 1521940 TI - Fluid replacement after dehydration: influence of beverage carbonation and carbohydrate content. AB - This investigation evaluated the effects of beverage carbonation and carbohydrate (CHO) content on fluid replacement following exercise/thermal dehydration. On four occasions separated by at least 7 days, eight healthy men cycled at 50% of VO2max in a hot environmental chamber (40 degrees C, 40% relative humidity) until a weight loss of 4.12 +/- 0.22% was attained. In the subsequent four hours, subjects ingested one of four solutions at 15-min intervals. The total volume ingested equalled that lost during dehydration. The solutions were administered in randomized order and varied in their carbonation and carbohydrate (CHO) content: 1. CK: carbonated 10% glucose-fructose solution, 2. NCK: non-carbonated 10% glucose-fructose solution, 3. CNK: carbonated non-caloric solution, and 4. NCNK: non-carbonated non-caloric solution. Plasma volume changes, total plasma protein concentration, plasma osmolality, and the plasma glucose concentration were determined at rest before and after dehydration, and at 30, 90, 150, and 240 min of recovery. Plasma volume changes and the plasma protein concentration were not different (p greater than 0.05) between treatments. Values for the plasma glucose concentration and the change in plasma osmolality were significantly elevated when CHO beverages were ingested when compared with non-CHO beverage ingestion. Five-min cycling bouts were performed at 70% of VO2max before and after dehydration and at 60, 120, 180, and 240 min of rehydration. The respiratory exchange ratio was elevated in both of the CHO treatments when compared with both of the non-CHO treatments at 60, 120, 180 and 240 min of rehydration.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1521941 TI - Depressed systolic and diastolic cardiac function after prolonged aerobic exercise in healthy subjects. AB - We studied 11 healthy untrained volunteers (aged 28.9 +/- 4.6 years) during 60 minutes of aerobic ergometric exercise with constant heart rates of 130 to 140 beats/minute. We found a continuous and significant decrease in systolic and diastolic pressure from 175 +/- 18/77 +/- 7 mmHg in the 5th minute to 144 +/- 14/68 +/- 6 mmHg in the 60th minute of exercise. Cardiac function and structure were assessed by M-mode echocardiography before exercise, after 5 minutes and after 60 minutes of exercise at comparable heart rates. The results demonstrated significant decreases in cardiac output, ejection fraction, and diastolic posterior wall velocity and an increase in total peripheral resistance after 60 minutes of exercise. We conclude that the decrease in blood pressure during long term aerobic exercise in healthy untrained subjects might be at least influenced by a decrease in left ventricular filling and contractility, possibly indicating cardiac fatigue. PMID- 1521942 TI - Bioenergetic characteristics of swimmers determined during an arm-ergometer test and during swimming. AB - The maximal oxygen uptake (VO2max) of 13 swimmers was determined by an arm ergometer test (direct method) and estimated from a maximal multistage swimming test (indirect method) (23). A test-retest of the progressive swimming exercise showed that there were no significant differences from one test to the other and that there were significant correlations between the principal parameters: arm stroke index: 0.73, maximal aerobic swimming velocity: 0.94, VO2max: 0.95, p less than 0.01. Therefore, for swimmers of average ability, the reproducibility of this test has been proved. A significant difference (p less than 0.001) was observed between the two tests for VO2max: arm-ergometer test (VO2max arms): 2.4 +/- 0.5 l.min-1, swimming test (VO2max ST): 3.2 +/- 0.7 l.min-1, p less than 0.01. This difference appeared to be linked to the use of a greater muscle mass (arms and legs) during swimming. A significant correlation (r = 0.73, p less than 0.01) was obtained between VO2max (l.min-1) by using both the direct and indirect exercises as methods of measurement. However, the level of r did not permit the prediction of one parameter from the other. Significant correlations were obtained between VO2max and performances over 200 and 400 m free style regardless of the methodology used (VO2max arm, VO2max ST). Moreover, only VO2max (arm, ST) emerged as a variable accounting for swimming performance from a step-wise multiple regression analysis, in which biometric and bioenergetic parameters were taken into account. PMID- 1521943 TI - A simple method for gender verification based on PCR detection of Y-chromosomal DNA and its application at the Winter Universiade 1991 in Sapporo City, Japan. AB - A simple and reliable screening method for gender verification at international sports competitions was developed on the basis of detection of Y-chromosomal DNA which was specifically amplified by polymerase chain reaction (PCR). Total DNA obtained from buccal mucous membrane cells by digestion with proteinase K followed by boiling treatment was directly used for the PCR. The amplified product was electrophoresed on an agarose gel staining with ethidium bromide. We adopted three sets of the PCR primer, identifying different regions of Y chromosome, of which sensitivity and specificity were preliminary evaluated for 228 (112 male, 116 female) DNA samples from lymphocytes. This new method was first applied for the gender verification test at the Winter Universiade 1991 Sapporo, accompanied by traditional microscopic tests for X- and Y-chromatins. No positive results were obtained for 155 female competitors using both the PCR and the microscopic methods. The superiority of the proposed method was clearly shown in the reliability of the results and also in the saving on instrumental and personnel costs as compared to previous cytologic methods. PMID- 1521945 TI - Effect of training on the calf muscle energy metabolism. A 31P-NMR study on four elite downhill skiers challenged with a standardized exercise protocol. AB - This study evaluates the effects of a 6 months' training period on the bioenergetics of the calf muscle of elite athletes by means of phosphorus-31 Nuclear Magnetic Resonance Spectroscopy (31P-NMR). Four downhill skiers, belonging to the Spanish National Team, performed a standardized exercise protocol using their right leg inside a wide-bore 2.35 Tesla magnet. The inorganic phosphate/phosphocreatine (Pi/PC) ratio and intracellular pH (pHi) were measured at steady-state during an exercise protocol composed of 5 work levels between 20% and 80% of the maximum voluntary contraction (MVC), before and after the training period. The measured values, which were markedly scattered at the beginning, regrouped after training. This was caused by a shift towards lower Pi/PC ratios and by a lower pHi acidification in three of the four subjects. This result suggests that 31P-NMR is a good tool to evaluate changes in the muscle aerobic capacity of athletes induced by training. PMID- 1521944 TI - Effects of captopril chronic intake on the aerobic performance and muscle strength of normotensive trained subjects. AB - Fifteen normotensive athletes specializing in dynamic sports took part in a randomized double-blind and cross-over study: captopril (50 mg/24 h) vs placebo. Each treatment lasted one month. Maximal exercise tests on cycle ergometer were performed at the end of each period. No significant differences were observed in the maximal values of oxygen uptake, power, heart rate or blood lactate value. The anaerobic threshold, defined as the exercise intensity which corresponded to a 4 mmol.l-1 blood lactate level was unchanged. With captopril, the end-of exercise systolic and diastolic BP were slightly altered (NS). Lower limb muscle strength, as explored with a Cybex isokinetic system, was not modified by captopril intake. The results indicate that maximal aerobic performance and isokinetic strength of the lower limbs are not altered by captopril chronic administration (50 mg/day) in normotensive trained subjects. PMID- 1521946 TI - Body fat estimations by electrical impedance and infra-red interactance. AB - The purpose of this study was to examine body fat estimation using three methods of electrical impedance (the BIA-103 Body Composition Analyser--RJL Systems, Detroit; the BMR 2000 Body Composition Analyzer--Berkeley Medical Research, San Leandro; the BC300 Body Composition Analyzer--Spacelabs, Dallas) and an infra-red interactance method (Futrex 5000 Analyzer--Futrex Inc. Gaithersburg) as an alternative to hydrodensitometry. Five different groups were examined using at least one of the electrical systems and in all cases utilising hydrodensitometry as the criterion method. The results produced highly significant correlations between all methods, but caution is recommended due to the limited common variance in some cases. The individual electrical methods differed from hydrodensitometry by a maximum of 1.1% in obese women, by 21.6% in athletic adults, by 6.2% in the slightly obese group, by 8.1% in normal women and by 56.0% in normal children. Significant mean differences between one of the impedance methods and hydrodensitometry were only noted in two of the groups tested. This suggests, allowing for the limitations of hydrodensitometry itself, that the other three electrical methods appear to be reasonably valid alternatives to underwater weighing, especially for field work of an epidemiological nature. PMID- 1521947 TI - Cortisol levels during prolonged exercise: the influence of menstrual phase and menstrual status. AB - The purpose of this study was to determine the influence of menstrual phase and menstrual status on the cortisol response during 90 minutes of treadmill running at 60% VO2max. Eight eumenhorrheic athletes were tested in the early follicular (EF) (day 3-5), late follicular (LF) (day 13-15) and mid-luteal (ML) (day 22-24) phases. Six amenorrheic athletes were tested on two separate occasions. The resting cortisol levels were similar in each menstrual phase and overall a decreasing pattern of cortisol response to exercise was observed in all menstrual phases (P greater than .05). The amenorrheic athletes had a significantly greater (P less than .01) pattern of cortisol response than was observed in eumenorrheic athletes. The net increment in cortisol levels during exercise were distinctly greater (P less than .01) in amenorrheic than eumenorrheic athletes (amenorrheic: 413.8 +/- 113.1, eumenorrheic: EF: -482.8 +/- 88.3, LF: -311.8 +/- 102.1, ML: 386.3 +/- 146.2 nmol.l-1). In conclusion the cortisol levels are independent of menstrual phase. Also a larger cortisol increment is observed in amenorrheic athletes in response to prolonged submaximal exercise. The elevated cortisol levels in amenorrheics at rest and throughout exercise provides further evidence that disturbances in the hypothalamic-pituitary-adrenal function are associated with exercise-induced amenorrhea, although the site(s) of physiological disturbance have not been identified. PMID- 1521948 TI - Biochemical, hematological and endocrinological parameters during repeated intense short-term running in comparison to ultra-long-distance running. AB - In order to see the differences in the acute effects of two kinds of running on biochemical, hematological and hormonal parameters, we investigated in one 24 h race (same exterior conditions) two groups of runners (NR = nonstop runners; RR = relay runners). From each participant blood samples were taken before, 3 times during and after the race. In both groups the lipid parameters cholesterol, triglycerides and LDL-cholesterol declined significantly, triglycerides even to 40% of their initial value, whereas HDL-cholesterol increased significantly. Renal parameters showed similar increases in both groups except for uric acid, which rose by 73% in RR compared with only 23% increase in NR. A difference was also found in the lactate and glucose concentrations, showing a four-fold increase and a 34% increase at 4 h respectively in RR, whereas the NR remained constant. Changes in the hematological parameters were similar in both groups. Cortisol and prolactin showed similar alterations during the race but LH and testosterone declined to approximately half of their initial concentration (p greater than 0.05) in NR after 4 to 8 h, in contrast to RR, where the concentration of LH or testosterone remained constant or changed only moderately but insignificantly during the race. Our investigation indicates that in ultra long-distance running and intense short-term exercise performed under the same exterior conditions, many parameters show similar changes but great differences can be found as well if certain hormones, glucose metabolism and renal parameters are considered. PMID- 1521949 TI - 'Sports anemia'--a real or apparent phenomenon in endurance-trained athletes? AB - In order to critically define the apparently widespread condition 'sports anemia', the red cell indices and iron status of male distance runners and triathletes, and female distance runners and ballet dancers were compared to non exercising controls of both sexes. The mean hemoglobin (Hb) levels of all groups were within the normal ranges and there was no difference between the athletic and control groups of each sex. The mean serum ferritin (SF) concentration of the male distance runners (79.8 micrograms/l) was significantly lower than that of the triathletes (123.5 micrograms/l) and controls (138.3 micrograms/l). Iron deficiency (SF less than 12 micrograms/l, % saturation less than 18%) was evident in 3.3% and 5% of the male and female runners respectively, and 3.3% of the ballet dancers. Iron deficiency anemia (abnormal red cell indices and iron status) occurred in only 1.7% and 3.3% of the male and female distance runners respectively, and 3.3% of the dancers. However, 7 (11.7%) each of the male and female distance runners and 6 (20.0%) of the ballet dancers recorded hemoglobin values lower than the normal range of 140 g/l and 120 g/l for males and females respectively. This anomaly can be explained by a significantly expanded plasma volume in endurance-trained individuals, causing a 'pseudoanemia'. We conclude therefore that athletes are at no greater risk for developing a frank anemia than the non-exercising population, and that the term 'sports anemia' is misleading, as it does not describe a specific clinical entity. PMID- 1521950 TI - Serum keratan sulfate levels in marathon runners. AB - The effect of strenuous joint loading on the metabolism of articular cartilage in man is not known. The development of a non-invasive immunoassay for the assessment of the catabolism of cartilage aggrecan has enabled us to quantify keratan sulfate (KS), a component of aggrecan, in the serum of fifteen male marathon runners. Serum KS was measured by an ELISA before and immediately after a marathon (42 km), as well as 48 hours after the completion of the race. The mean level at rest was similar to those previously reported for another population of age-matched males. There was no statistically significant difference in the serum level of KS at the three different readings. Further, there was no correlation between age, height, weight and performance time, and the serum level of KS at any of the three different times. We conclude that marathon running by carefully trained runners causes neither a transient nor a sustained increase in proteoglycan catabolism in articular cartilage. PMID- 1521951 TI - Hand injuries in volleyball. AB - We studied the long-term sequelae of hand injuries as a result of playing volleyball. In a retrospective study, 226 patients with injuries of the hand who were seen over a 5-year period at our Trauma Department, were investigated. Females accounted for 66% of all injuries. The mean age was 26 years, with a peak in the age group of 15 to 29 years. Sprains and strains were observed most frequently (39%), followed by fractures (25%) and contusions (16%). The fingers were involved in 44% of the cases. Most injuries of the hand occurred in recreational players. Recreational players had more left-sided injuries, whereas competition players had more right-sided injuries (P less than 0.005), suggesting that lack of skill is an important determinant. Left-handedness was associated with an increased risk of hand injury in recreational players. One third of the volleyball players did not go to work or school for a median of 4 weeks as a result of the injury. In a survey after a mean period of 5 years, a high percentage of patients had complaints: 28% cited stiff and crooked fingers with limitations and tenderness in the movements as main inconveniences. We consider this incidence disturbingly high, regarding the seemingly innocent nature of these injuries. PMID- 1521952 TI - A simple method for determining critical speed as swimming fatigue threshold in competitive swimming. AB - The purpose of this investigation was to determine whether the concept of the critical power could be applied to competitive swimming by using critical swimming speed (CS) as determined both in the swimming flume (CS-flume) and in the normal swimming pool (CS-pool) and whether CS could be utilized as a practical index for assessing a swimmer's endurance performance. CS defined as the swimming speed which could be theoretically maintained continuously without exhaustion was expressed as the slope of a regression line between swimming distance (D) and its duration (T) obtained at various swimming speeds. Eight highly trained swimmers were instructed to swim until onset of fatigue at four predetermined swimming speed levels in the swimming flume and at maximal effort over four different swimming distances in the swimming pool. In the results of CS flume and CS-pool, the regression relations between D and T were expressed in the general form, D = a+b x T, with r2 being higher than 0.998 (p less than 0.01), respectively. These results both from the flume and the pool indicated extremely good linearity. Furthermore, maximal oxygen uptake (VO2max) during the incremental exercise test, swimming speed corresponding 4 mM of blood lactate concentration (V-OBLA) and mean velocity in the 400 m freestyle (V-400) were measured on each subject.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1521953 TI - Performance measures, blood lactate and plasma ammonia as indicators of overwork in elite junior weightlifters. AB - The effects of short-term overwork on performance measures, blood lactate, and plasma ammonia concentrations were examined in 28 elite junior weightlifters who participated in a 2 wk high volume resistance training camp. Performance testing (maximum effort vertical jump test and snatch lift) and blood chemistry analyses (ammonia and lactate) were conducted before (T1) and after (T2) 7 d of high volume training (2-3 workouts/d). Blood samples were collected from an antecubital vein at rest, preexercise, 5 min postexercise, and 15 min postexercise at T1 and T2. Results indicated a significant decrease from T1 to T2 in the maximum effort vertical jump test while the snatch lift test yielded no difference across time. Blood lactate and ammonia concentrations were significantly lower at 5 min postexercise at T2 while resting ammonia concentrations were significantly elevated at T2 compared to corresponding measures at T1. These data suggest possible early symptoms of overwork at T2 (decrease in performance of the maximum effort vertical jump test and the elevated resting ammonia concentrations); however, lower 5 min postexercise concentrations of lactate and ammonia at T2 indicated a positive adaptation to the 1 wk high volume resistance training period. PMID- 1521954 TI - The effect of training intensity on ratings of perceived exertion. AB - We examined the effects of intensity of training on ratings of perceived exertion (RPE) at the lactate threshold (LT), fixed blood lactate concentrations (FBLC) of 2.0, 2.5 and 4.0 mM and peak in 25 untrained eumenorrheic women (mean +/- SD: age = 30.9 +/- 4.1 yrs; height = 165.7 +/- 5.9 cm; weight = 65.5 +/- 7.6 kg) who completed one year of run training. Subjects were recruited as sedentary controls or were randomly assigned to one of two training groups: 1) at the lactate threshold (at LT) or 2) above the lactate threshold (greater than LT). The at LT group trained at velocity LT and the greater than LT group trained at the velocity midway between velocity LT and peak velocity. Training subjects were reevaluated every fourth menstrual cycle and training intensity was adjusted. The control group was reassessed at menstrual cycle 12. Before training no among group differences were observed for VO2 or velocity at LT, FBLC and peak. Both training groups increased VO2 at LT, FBLC and peak as a result of training (p less than 0.05), with the greater than LT group exhibiting greater improvement than the at LT group (VO2 at LT, FBLC of 2.0, 2.5 and 4.0 mM and peak increased by 6.4, 5.3, 5.1, 4.0 and 4.7 ml/kg.min-1 for at LT and by 10.4, 9.2, 8.6, 5.1 and 5.9 ml/kg.min-1 for greater than LT; p less than 0.05). Similar findings were observed for the velocity associated with these lactate concentrations. No pre/post differences were observed in VO2 or velocity for the control group.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1521955 TI - Cardiac responses of young women to conditioning for a 10 kilometer race. AB - Seven previously sedentary women (mean age, 19 yrs) participated in an 11-week running program (4-5 sessions/week) in preparation for a 10 km race. Training intensity was 80-85% of maximum heart rate reserve. Exercise duration began at 20 minutes/session and was lengthened 5 minutes/session every 2 weeks. A control group consisting of 4 women was also evaluated. Maximal oxygen uptake (VO2max, ml/kg/min) increased 11% in the trained group and decreased 6% in the control group during the study (p less than 0.05). Oxygen uptake, cardiac output (Q), and stroke volume (SV) increased significantly (p less than 0.05) in the trained group during each of 3 levels of steady state cycle ergometer exercise (heart rate targets: 115, 135 and 155 beats/min, respectively). Arteriovenous oxygen difference (a-V02 diff) was not increased significantly after training. Resting left ventricular dimensions and performance evaluated by echocardiography also did not change significantly after training. It was concluded that short-term conditioning in this population results in an increased exercise Q without concomitant increases in left ventricular dimensions or arteriovenous oxygen difference. PMID- 1521956 TI - Characterization of the heart rate response during biathlon. AB - Continuous heart rate recordings were obtained on elite American bi-athletes during competitions to provide a better understanding of the physiological demands of biathlon and the strategies used in approaching the shooting range. The findings demonstrate that the average age heart rate during skiing was approximately 90% of maximum heart rate. Heart rates decreased 10-12 bpm over a time period of approximately 50-60 sec during the approach to the firing line. At arrival to the firing line, heart rates were similar for prone and standing shooting averaging 85-87% of maximum heart rate. Mean minimum heart rates while at the firing line dropped to 61-73% of maximum heart rate and averaged approximately 20 bpm lower for prone shooting. The lower minimum heart rates during prone shooting were accounted for by the bi-athletes spending a longer time at the firing line and having a more rapid decrease in heart rate while in the prone position. PMID- 1521957 TI - The influence of the fullness of milk in the breasts on the concentration of lactic acid in postexercise breast milk. AB - The purpose of this study was to observe the influence of the fullness of breast milk in the breasts prior to exercise on the concentration of lactic acid in breast milk following exercise. Twenty-three lactating women were randomly assigned to Group E (n = 11), which nursed and/or collected as much of the breast milk as possible prior to maximal exercise, and Group F (n = 12), which did not nurse or collect milk at least two hours prior to maximal exercise. Milk was collected at rest preexercise and 10, 30, 60 and 90 minutes postexercise and was analyzed for concentrations of lactic acid. ANOVA demonstrated 1) a significant increase in lactic acid in the milk at all postexercise collections for both groups and 2) a significant group vs postexercise time interaction for lactic acid concentration in milk. These differences represented differences in 1) time to peak lactic acid concentrations in milk (Group F = 10 min; Group E = 30 min) and 2) time for postexercise decreases in lactic acid concentrations in milk. Thus, the state of fullness of milk in the breasts is a factor which affects the concentration of lactic acid in breast milk following maximal exercise. PMID- 1521958 TI - Rehydration after exercise with common beverages and water. AB - This study assessed the effectiveness of two common rehydration beverages (a caffeinated diet cola (DC) and a 6% carbohydrate-electrolyte (CE) solution) compared with water (W) for whole body rehydration, gastric emptying and blood volume (BV) restoration during a 2 h rehydration period following exercise induced dehydration. Subjects (mean VO2max = 4.2 +/- 0.6 l.min-1.min-1; n = 19) exercised at 60-80% VO2max in the heat (32 degrees C; 40% rh) until approximately 2.5% (1.95 +/- 0.12 kg) of their body weight (BW) was lost. After exercise, the subjects sat for 2 h in a thermoneutral environment (21 degrees C; 60% rh) and drank a volume of DC, W and CE equal to the fluid lost. Fluids were consumed in two boluses averaging 1,046 +/- 198 and 912 +/- 186 ml at 0 and 45 min of the 2 h rehydration period, respectively. At the end of the rehydration period, no fluid remained in the stomach during any of the trials as indicated by epigastric impedance. However, in all the trials the subjects were somewhat hypohydrated (range 0.6-0.9 kg BW below euhydrated BW; p less than 0.05) after the 2 h rehydration period since additional water and BW were lost as a result of urine formation, respiration, sweat and metabolism. The percentage of body weight loss that was regained (used as an index of % rehydration) during DC (54 +/- 5%) was significantly lower than that of W and CE (64 +/- 5% and 69 +/- 5%, respectively; p less than 0.05; n = 10).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1521959 TI - Load and velocity of contraction influence gross and delta mechanical efficiency. AB - The effects of three different cadences and five different work rates on Gross (GE) and Delta Efficiency (DE) during cycle ergometry were studied. Fifteen well trained cyclists exercised for 30 minutes at 60, 80, or 100 RPM on three different occasions. On each occasion, the load was increased every five minutes and corresponded to approximately 50, 60, 70, 80 and 90% of VO2max. During the last three minutes of each stage, steady-state energy expenditure was calculated while work rate was recorded. In addition, the oxygen cost of unloaded cycling (CUC) was also measured. GE was calculated as the ratio of work rate to the rate of energy expenditure, whereas DE was calculated as the reciprocal of the slope of this relationship at work rates between 50 and 90% of VO2max. The CUC corresponded to 0.66 +/- 0.03 l/min, 0.77 +/- 0.04 l/min and 1.04 +/- 0.04 l/min at 60 RPM, 80 RPM and 100 RPM, respectively (p less than 0.01 for all comparisons). GE was similar at all cadences when cycling at 80 and 90% VO2max. DE increased with increasing rpm and corresponded to 20.6 +/- 0.4%, 21.8 +/- 0.6%, and 23.8 +/- 0.4% at 60 RPM, 80 RPM and 100 RPM, respectively (p less than 0.01 for all comparisons). Therefore, when trained cyclists exercise intensely (80-90% VO2max), GE is similar at cadences of 60, 80 and 100 RPM, despite the significant increase in the CUC. Thus, it is possible that delta efficiency increases with increasing cadence. PMID- 1521960 TI - Exercise training-induced alterations in skeletal muscle oxidative and antioxidant enzyme activity in senescent rats. AB - Limited data exist concerning exercise training-induced alterations in skeletal muscle oxidative and antioxidant enzyme activity in senescent animals. Therefore, the purpose of this study was twofold: 1) to examine the exercise training induced changes in oxidative and antioxidant enzyme activity in skeletal muscle of old rats; and 2) to critically analyze the relationship between oxidative and antioxidant enzyme activities in skeletal muscle in both trained and untrained senescent rats. Female Fischer-344 rats (approximately 24-mo-old) were divided into 1) exercised trained (ET; n = 10) and 2) sedentary (S; n = 6) groups. The ET rats performed a 10-week training program of treadmill exercise (approximately 60 min, 5 days/wk). Training significantly (p less than 0.05) improved VO2max (delta 22.8%) in the ET rats above their age-matched controls. Further, the ET group had significantly elevated (p less than 0.05) activities of succinate dehydrogenase (SDH) in the soleus and red gastrocnemius (RG) muscles as well as greater (p less than 0.05) 3-hydroxyacyl-CoA dehydrogenase (HADH) activity in the RG when compared to the S group. However, training did not alter (p greater than 0.05) HADH activity within the white gastrocnemius (WG) or soleus muscles. Activity of the antioxidant enzyme, glutathione peroxidase (GPX) was higher (p less than 0.05) in the soleus and RG in ET rats when compared to the S rats; in contrast, training did not alter (p less than 0.05) GPX activity in the WG. Finally, the correlation coefficients between SDH and GPX activities (combined ET and S groups) for the RG, WG, and soleus muscles were r = .73, .17 and .36, respectively.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1521961 TI - NMR spectroscopy study of heart phospholipids. An exercise and anabolic steroids effect. AB - Because 31P NMR spectral analysis of phospholipid (PL) is an accurate and rapid technique for resolving the quantity of PL resonances and involving minimum chemical manipulations that may affect the integrity of the tissue (24-26), we studied the effect of anabolic steroid injection, exercise training, or a combination of both treatments on whole heart phospholipids using 31P NMR spectral analysis. Male Sprague-Dawley rats were randomly assigned to 4 groups of 11 each: sedentary control (C), steroid-treated (ST), exercise-trained (E), and exercise plus steroid-treated (ES). The ST and ES rats were administered nandrolone decanoate by i.m. injection every 7-9 d during the 10 wk study, while the C and E rats were injected with glycerol. The exercise rats ran on a treadmill, wearing a collar weight for 50 min/day, 5 days/wk. There was a significant difference in body wt among the four groups at the conclusion of the study; however, no significant differences in heart wt or in the ratio of heart wt:body wt were observed among the four groups. Myocardial phospholipid profiles of the exercise-trained rats were significantly (p less than 0.05) different from those of the untrained rats. The changes were enhanced somewhat by the steroid treatment. The profiles differed in the relative amounts of four of the nine myocardial phospholipids detected: phosphatidylcholine, phosphatidylethanolamine (PE), PE plasmalogen, and phosphatidylserine. We conclude that the observed changes in whole heart phospholipid compositions are due to experimental treatment specifically from exhaustive exercise and not from anabolic steroids or cardiac hypertrophy.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1521962 TI - The influence of diabetes mellitus on cardiovascular function in children and adolescents. AB - Early manifestations of non-atherosclerotic cardiomyopathy, a recognized complication of diabetes in adults, have been suggested to contribute to depressed levels of aerobic fitness described in children and adolescents with this disease. This study measured components of aerobic fitness and cardiovascular function during maximal cycle ergometer exercise in 11 insulin dependent diabetic boys aged 10.2-16.5 years. Mean duration of diabetes was 4.5 years. Eleven non-diabetic subjects matched for age, body size, and regular physical activity served as controls. No differences in maximal oxygen uptake or heart rate were observed between the two groups, nor were any significant differences recorded in submaximal stroke volume, cardiac output, heart rate, and pressure-rate product. This study failed to reveal any evidence of functional myocardial disease in children and young adolescents with diabetes, suggesting that manifestations of diabetic cardiomyopathy should not be expected during the pediatric years. Moreover, these findings indicating normal cardiovascular function in young diabetic subjects imply that regular levels of habitual physical activity are more likely to affect aerobic fitness in these patients rather than influences of the diabetic state itself. PMID- 1521963 TI - Altered cellular distribution of hexokinase in skeletal muscle after exercise. AB - The purpose of this study was to determine the effects of a single period of swim exercise to exhaustion on the cellular distribution of hexokinase in rat skeletal muscle. The gastrocnemius muscle from male rats exercised (n = 16) to exhaustion or allowed to remain inactive (n = 14) was analyzed for hexokinase activity (HK) in the whole muscle homogenate and the mitochondrial-rich fraction. Although exercise produced a slight, non-significant, increase in HK activity in the whole muscle homogenate (p less than 0.09), HK activity in the mitochondrial-rich fraction was significantly increased in the exercised muscle (p less than 0.02). This shift in the cellular distribution of HK is towards the more active mitochondrial bound form and indicates an enhanced regulation of HK activity during physical exercise. PMID- 1521964 TI - Antioxidant status and cancer mortality in China. AB - Sex-specific mortality rates for selected cancer sites (including oesophagus, stomach, liver, lung, colorectum, breast and cervix) and a variety of biochemical indicators of antioxidant status, enzyme activity and oxidative stress (including plasma levels of beta-carotene, alpha-tocopherol, ascorbic acid, selenium, glutathione peroxidase, catalase, superoxide dismutase, iron, copper, zinc, total cholesterol and lipid peroxide) were examined in an ecological study of 65 mostly rural counties in the People's Republic of China. The wide range of both mortality rates and biochemical values and the measurement of a comprehensive set of biochemical indicators permitted both simple correlational and multivariate analyses of the joint and relative effects of each factor on site-specific cancer mortality. Plasma levels of dietary antioxidants were consistently negatively correlated with cancer mortality rates. Ascorbic acid was most strongly negatively associated with most cancers and selenium with oesophageal and stomach cancers. beta-carotene was found to have a protective effect independent of retinol, particularly for stomach cancer. PMID- 1521966 TI - Oesophageal cancer in the Republic of Karakalpakstan. AB - Regional and temporal patterns of variation in the incidence of cancer of the oesophagus in the Central Asian republic of Karakalpakstan were analysed. Karakalpakstan (population about 1200,000) is an area with high rates of this disease. Incidence data within regions (data from 1988-1989), ethnic groups (data from 1987-1989) and calendar periods (data from 1973-1987) were available for analysis, with corresponding official population estimates. No significant difference was observed between rates in urban and rural environments, although significant regional variation was observed (P less than 0.05). The highest rate observed was in the Muinak, the northern region, with world age-standardized rates (ASR) of 125.96 for males and 150.65 for females. There was a very significant difference among ethnic groups (P less than 0.001). The ethnic group with the highest incidence was the Kazakh people, with an ASR of 68.0 in males and 86.3 in females. Incidence in the republic as a whole declined in the period from 1973 to 1987. Incidence of cancer of the oesophagus is still high in Karakalpakstan, despite the decline. Incidence is likely to be strongly related to factors associated with region of residence and with ethnicity. PMID- 1521965 TI - Reduced risk of hip fracture in women with endometrial cancer. AB - The effect of excessive endogenous oestrogens on the risk of hip fracture was investigated in a population-based cohort of 2111 women with endometrial carcinoma who were followed up from age 50 years regarding the occurrence of a first hip fracture. Overall, 77 cases of hip fracture were observed, as against 120.8 expected, which meant a significantly reduced relative risk, standardized incidence ratio (SIR) = 0.6, 95% confidence interval (CI): 0.5-0.8. This possible protective effect was significant for cervical fractures, SIR = 0.6 (95% CI: 0.4 0.8), but not for trochanteric, SIR = 0.8 (95% CI: 0.5-1.1). Age at endometrial cancer diagnosis was not a determinant of the risk of hip fracture. A lowered relative risk was present regardless of age at diagnosis and persisted during the entire follow-up period and into advanced ages. A case-control analysis within the cohort, and based on medical record data, indicated that a higher weight might be associated with a greater protective effect, as compared with a lower weight. Exposure to exogenous oestrogens was infrequent and could not have explained the present results. We conclude that persistent influence of oestrogens, notably of endogenous origin, can reduce the risk of hip fractures, and that this protective effect may be long-lasting and extend to advanced ages. PMID- 1521967 TI - Assessment of the spatial occurrence of childhood leukaemia mortality using standardized rate ratios with a simple linear Poisson model. AB - Reports of a suspected cluster of childhood leukaemia cases in West Central Phoenix have led to a number of epidemiological studies in the geographical area. We report here on a death certificate-based mortality study, which indicated an elevated rate ratio of 1.95 during 1966-1986, using the remainder of the Phoenix standard metropolitan statistical area (SMSA) as a comparison region. In the process of analysing the data from this study, a methodology for dealing with denominator variability in a standardized mortality ratio was developed using a simple linear Poisson model. This new approach is seen as being of general use in the analysis of standardized rate ratios (SRR), as well as being particularly appropriate for cluster investigations. PMID- 1521968 TI - Body mass index and the initial manifestation of coronary heart disease in women aged 40-59 years. AB - A population-based case-control study was conducted to evaluate body mass as a coronary heart disease (CHD) risk factor among women 40-59 years of age. Cases were women aged 40-59 whose first manifestation of CHD was angina (No. = 133), nonfatal myocardial infarction (No. = 90), and sudden unexpected death (No. = 18) during 1960-1982. Two randomly selected controls were matched on age and time of the initial disease manifestation of the case. The adjusted relative risk for weight and body mass index respectively demonstrated a moderate association with all CHD as well as with angina, but no association with definite CHD (myocardial infarction or sudden unexpected death). To determine if the observed association between body mass index and angina was possibly attributable to differential misclassification bias (i.e. obese women were, in contrast to non-obese women, preferentially labelled as having coronary artery disease) data for angina were stratified by confirmed versus unconfirmed cardiac origin. In the unconfirmed angina analysis, the 75th percentile for weight contrasted with the 25th percentile was associated with a 50% increase in the risk of being labelled as having angina (adjusted odds ratio (OR) = 1.59, 95% confidence interval (CI): 1.11-2.28), while a similar contrast for Quetelet Index was also associated with a nearly 2-fold increase in the risk of being labelled as having angina (adjusted OR = 1.74, 95% CI: 1.18-2.57).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1521969 TI - Demographic and behavioural correlates of high density lipoprotein cholesterol. An international comparison between northern Italy and the United States. AB - Recently published results of longitudinal follow-up studies conducted in the US have identified high density lipoprotein (HDL)-cholesterol as an independent and strong predictive factor for coronary heart disease (CHD). Some inconsistencies in this association have been found when geographical comparisons were done, which could be explained by hypothesizing differences in population HDL cholesterol determinants. We carried out a comparative analysis of demographic and behavioural correlates of HDL-cholesterol between Northern Italy and the US, two countries with well-known differences in CHD risk and HDL-cholesterol levels. The study was conducted on representative samples of these two countries (MONICA Project-Area Brianza for Northern Italy and NHANES II for the US) and used comparable methodologies for data collection and statistical analysis. Results indicate that gender, age, body mass, cigarette smoking and alcohol consumption are independently associated with HDL-cholesterol in both populations; physical activity is positively, but not significantly, associated with HDL-cholesterol mean levels, and education achievement is independently associated only in the American sample. The comparison of the magnitude of the multivariate regression coefficients between the two studies suggests similar functional relationships for most of the correlates considered. The small, albeit significant, discrepancies found for body mass and smoking status could be related either to some methodological inconsistencies between the two surveys, or to possible effects of other covariates, not available to be tested in this study, like dietary habits. Moreover, HDL-cholesterol mean level differences between populations could be also due to differences in the prevalence of the examined correlates. PMID- 1521970 TI - Prevalence and control of hypertension in a large cohort of occupationally-active Israelis examined during 1985-1987: the Cordis Study. AB - In view of the many changes in the approach to the detection and management of hypertension that have occurred, the paucity of current data on this subject in Israel limits the possibilities of making international comparisons or evaluating trends. This study contributes recent information on the occupationally-active population. Between 1985 and 1987, blood pressures were measured and interview data obtained on awareness and treatment of hypertension in a sample of 3677 male and 1573 female employees in 21 Israeli industries, examined in the CORDIS Study. In the age group 35-64 years, the age-standardized prevalence of hypertension (greater than or equal to 160/95 mm Hg or treated) using the same standard population as the WHO MONICA Study was 17.1% for men and 16.1% for women. The prevalence for men was somewhat below the median country compared with the MONICA centres, whereas for women it was closer to the median. Marked ethnic differences were evident, with those of Western origin having the highest prevalence, and those of Asian origin, the lowest. Of the hypertensives, 35.6% of the men and 33.3% of the women were unaware of their condition. Among men aware, 82.8% were receiving treatment and 59.8% of them were under control; the corresponding percentages for women were 86.2% and 72.8%. Older people were more likely to be aware of their hypertension and receiving treatment. Beta-blockers and diuretics were the predominant drugs of choice.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1521971 TI - Habitual dietary calcium intake and blood pressure change around the menopause: a longitudinal study. AB - In a 10-year follow-up study, blood pressure and dietary intake were measured annually in 167 healthy perimenopausal normotensive women. Their initial ages ranged between 49 and 56 years and habitual calcium intake between 560 and 2580 mg/day (mean 1110 mg/day); they lived in the mixed rural/industrial community of Ede, the Netherlands. The longitudinal design provided an opportunity to study the 'natural history' of blood pressure and the effect of dietary calcium during and after the period of ovarian failure. For data analysis, person-time experience was divided into three menopausal periods. Based on years relative to menopause three menopausal cohorts were created starting 2 years before, 2 years after and 6 years after menopause, each was followed for 4 years. Changes in systolic (SBP) and diastolic blood pressure (DBP) during the menopausal periods were adjusted for change in body mass index and other relevant variables in multiple regression analysis. An average decline in SBP of 6 mm Hg was observed in the period of 2 years before menopause to 6 years after menopause, and an increase of almost 5 mm Hg in the period between 6 and 10 years after menopause. A significant change in DBP was not observed. Neither changes in, nor the absolute level of, calcium intake showed any relevant association with blood pressure change. Ovarian failure seems to reverse temporarily the increase in blood pressure due to aging. The results do not suggest that a habitual calcium intake exceeding 800-1000 mg/day (the current Recommended Daily Allowance for adults) is effective in preventing hypertension during the peri- and postmenopausal period. PMID- 1521972 TI - Changing trends in mortality among New Mexico's American Indians, 1958-1987. AB - Health care availability and living conditions have improved substantially for American Indians in New Mexico over the past quarter century. To investigate the impact of these changes on health statistics, we examined mortality data collected from 1958 to 1987 for American Indians in the state. We analysed the data for all causes of death combined and for specific causes, and compared these data with figures for nonHispanic whites in the state. Age-adjusted mortality rates were calculated for 5-year periods for each ethnic-gender group, using denominators from US Census reports. Mortality rates for all causes combined did not improve significantly for American Indian males from 1958 to 1987, although the rates for American Indian females showed an 8% decline. Infectious disease related mortality rates for American Indians decreased dramatically over the 30 year study period; however, mortality rates for cancer and diabetes increased over the 30-year period. Mortality rates for injuries and alcoholism among American Indians increased greatly from 1958 to 1977 and then declined later in the study period, but they were consistently higher than rates for whites. The study indicates that several chronic diseases remain of major public health importance for New Mexico's American Indian population. PMID- 1521973 TI - Compliance with a 12-month assessment in an elderly cohort participating in a preventive intervention study: the San Diego Medicare Preventive Health Project. AB - Non-compliance in long-term cohort studies contributes to bias in the estimation of study parameters and loss of power in hypothesis testing. This paper identifies baseline factors associated with non-compliance in a 12-month health assessment among elderly participants in the San Diego Medicare Preventive Health Project, a randomized preventive intervention study. A non-complier was defined as a study subject contacted by telephone by study personnel to schedule an appointment for the 12-month health assessment but who would not or could not attend. Of the almost 1600 contacted subjects, 14.1% did not participate in the evaluation. Using logistic regression, non-compliance was found to be associated with older age, intervention group assignment, nonsingle family residence, no alcohol use, and, to a lesser extent, depression. No interactions between group assignment and other baseline factors were detected. These results may be useful in designing cohort maintenance strategies where greater resources may be devoted to participants at higher risk of non-compliance and attrition. PMID- 1521974 TI - Use of positive-negative deviant analyses to improve programme targeting and services: example from the TamilNadu Integrated Nutrition Project. AB - This paper describes the characteristics of southern rural Indian children who grow best (positive deviants) and worst (negative deviants) as compared to median growers. A 100 each of positive and negative deviants and 120 median growers were selected after analysing the 12-month growth patterns (weight-for-age) of 2954 children enrolled in the TamilNadu Integrated Nutrition Project (TINP), a major health and nutrition intervention project covering nearly one million children in rural south India. The determinants of poor growth that have been left unaddressed by 6 years of TINP exposure are delineated to address the question of what more needs to be done. Further, the rationale for differential targeting of services to negative deviants and to median growers is discussed, as are the implications for programme evaluation. Data indicate that the next generation of projects targeted at the most needy (negative deviants) should address the issues of gender discrimination in childcare, of breastfeeding, of diarrhoeal disease, and of maternal empowerment. Such interventions will, however, not improve the growth of median growers in the direction of positive deviance. Instead, programmes targeted at the median growers need to support the hygienic use of nonbreast milk supplements. Improving family wealth will also improve the nutritional status of the median growers, but less so than for the negative deviants. PMID- 1521975 TI - Space time clustering of births in SIDS: do perinatal infections play a role? AB - The aetiology of sudden infant death syndrome (SIDS) remains uncertain; many causal pathways have been proposed. In this paper we have examined firstly the variation in the risk of SIDS with age, month of death and month of birth; and secondly the space time clustering of SIDS deaths, and, separately, space time clustering of their births. Data were obtained from the Office of Populations, Censuses and Surveys on all certified SIDS deaths in the period; children were assigned grid references for the address of birth and of death. Data on number of births were abstracted from published material. A log-linear modelling technique was used to investigate the separate effects of age, month of death and month of birth on the risk of SIDS. The Knox method was used to investigate space time clustering of deaths and of births of children who died of SIDS. Separate, statistically significant effects were found for age, month of death and month of birth. There was minor space time clustering of SIDS births and deaths at large time and space intervals, and a marked space time clustering of births in short space time intervals in the first quarter of the year. The finding of an effect of month of birth on the risk of SIDS, and of space time clustering of births suggest that a perinatal hazard--possibly of infectious origin--may play a role in the aetiology of SIDS. PMID- 1521976 TI - Mother's education and perinatal problems in Finland. AB - This study using nationwide data expands a previous study from one area in Finland. The purpose was to study how perinatal problems (mortality, short gestation, low birthweight and low Apgar scores) vary by mother's social class, which is measured by level of education. Outcomes of all births in the 1987 Medical Birth Register were linked to the 1988 National Education Register with gives the estimated number of years of completed education. In unadjusted analyses, the lowest educational groups (less than 9 years) had the worst results for outcomes other than neonatal mortality. Results in the two highest educational groups (greater than or equal to 13 and 12 years of education) were similar and if anything, better in the second highest group. Excluding twins and adjusting for confounding variables (age, parity, county, urbanization of residence) by logistic regression analysis did not alter the results much. Adjustment for possible mechanisms correlated with social class (marital status, smoking, time of first antenatal visit) decreased the higher occurrence of low birthweight infants in the low educational groups. Reported previous miscarriages were more common in the higher educational groups. Based on the available background characteristics one would expect to have found the usual social gradient in perinatal problems to have persisted between the two highest educational groups. Further studies on factors causing the plateau in the gradient between these groups might be useful. PMID- 1521977 TI - Ancestral origin of insulin-dependent diabetes in Mexican-Americans. AB - To test the hypothesis that insulin-dependent diabetes mellitus in the Mexican American population is due to Spanish genetic admixture, we obtained ancestral information on 106 Mexican-American families with an insulin-dependent diabetic index case and 80 Mexican-American control families from 1987 to 1991. The Mexican states of origin were available on 395 grandparents of the insulin dependent diabetic index cases and 291 grandparents of the controls. Analysis of the individual states of origin revealed that there were significantly more Mexican-American grandparents of diabetic index cases from the states of Jalisco and Michoacan when compared to the control families (31% and 16% diabetic versus 22% and 11% controls respectively, P less than 0.01). The states of Zacatecas and Durango had a lower frequency of diabetic grandparents as compared to controls (6% diabetic versus 12% controls, P less than 0.001). Analysis of the origin by Northern and Southern states of Mexico revealed a significant decrease in the number of grandparents of the insulin-dependent diabetic cases from the Northern regions of Mexico, 19.5%, versus 32% in controls, (P less than 0.001). These data indicate that the grandparents of the insulin-dependent diabetic index cases originate from states and regions of Mexico which were those of the early entry of the Europeans. These data thus support the hypothesis that insulin-dependent diabetes mellitus in the Mexican-American population may be due in significant part to an original genetic contribution from the Spanish-European population. PMID- 1521978 TI - Prevalence of diagnosed diabetes in circumpolar indigenous populations. AB - The prevalence of diagnosed diabetes in several genetically closely related indigenous populations in the circumpolar arctic and subarctic regions of Russia, Alaska and Canada is compared. The age-standardized (to the IARC's hypothetical world population) prevalence ranged from 1.8/1000 among the Chukchi and Eskimo of Chukotka, 3.6 and 7.9/1000 among the Eskimos/Inuit of the Canadian Northwest Territories (NWT) and Alaska respectively, 7.1, 9.3 and 18.6/1000 among Athapaskan Indians in the NWT, Yukon and Alaska respectively, to a high of 22.7/1000 among the Aleuts in Alaska. All are below the US all-race prevalence of 23.5/1000 and far below the extreme high prevalence reported from many North American Indian tribes. As a group, such arctic and subarctic peoples have a much shorter and less intense history of European contact and acculturation. Environmental factors are also likely to be responsible for the current differences between these indigenous populations in the circumpolar region, assuming that they share susceptibility genes for diabetes inferred from their close genetic relationships based on markers in other loci. Formal surveys of glucose tolerance and potential risk factors such as diet, physical activity, obesity, insulin resistance and genetic admixture in the circumpolar region would improve knowledge of the aetiology of diabetes in genetically and culturally diverse human populations. PMID- 1521979 TI - Markers of risk of asthma death or readmission in the 12 months following a hospital admission for asthma. AB - A case-control study has previously been reported of asthma deaths in people aged 5-45 years who had a hospital admission for asthma (the index admission) in New Zealand during 1981-1987. The study has been re-analysed to examine the association between markers of asthma severity and risk of asthma death or hospital admission; patients prescribed fenoterol were excluded from this re analysis because of the previously reported interaction between fenoterol, asthma severity, and asthma deaths. The re-analysis included 39 patients who died of asthma during the 12 months after their index admission, 226 patients who had a readmission for asthma during the 12 months after their index admission, and 263 controls chosen from all index admissions. An admission in the previous 12 months was the strongest marker of subsequent risk of death (odds ratio (OR) = 3.5, 95% confidence interval (CI): 1.8-6.9, P less than 0.01), and was also a strong marker of subsequent risk of readmission (OR = 3.0, 95% CI: 2.1-4.2, P less than 0.01); the risk increased with the number of previous admissions. Three or more categories of prescribed asthma drugs was also associated with subsequent death (OR = 1.7, 95% CI: 0.9-3.3, P = 0.13) or readmission (OR = 1.9, 95% CI: 1.3-2.7, P less than 0.01); prescribed oral corticosteroids was only weakly associated with subsequent death (OR = 1.3, 95% CI: 0.6-2.8, P = 0.59), but was more strongly associated with subsequent readmission (OR = 1.9, 95% CI: 1.2-2.8, P less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1521980 TI - Epidemiological study of the cardiovascular effects of carbon disulphide. AB - In an extensive health survey 115 male viscose rayon workers exposed to carbon disulphide (CS2) and 76 referents not exposed to this chemical were interviewed using the WHO cardiovascular questionnaire and responded to a self-administered questionnaire. A 12-lead ECG was taken and coded using the Minnesota code. Blood pressure (BP) was measured electronically and blood was examined for lipoproteins. In the viscose rayon factory the working conditions had not changed since 1932. Personal monitoring performed in 17 jobs, showed exposures varying from 4 to 112 mg/m3. For each individual a CS2 cumulative exposure index (CS2 index) was calculated. There were no significant differences between exposed and referents concerning the prevalence of angina, history of myocardial infarction, intermittent claudication and ECG signs of ischaemia. Blood pressure, low density lipoprotein (LDL)-cholesterol and the apolipoproteins A1 and B rose while high density lipoprotein (HDL)-cholesterol, the HDL-cholesterol/apolipoprotein A1 and the LDL-cholesterol/apolipoprotein B ratios decreased significantly with increasing exposure. Adjustment for age, body mass index, smoking, alcohol consumption, stress and tension at work, shift work, noise exposure and educational level in multiple linear regression analysis showed significant effects of the CS2 index on systolic BP, diastolic BP, cholesterol, HDL cholesterol, LDL-cholesterol, apolipoprotein A1, apolipoprotein B, the LDL cholesterol/apolipoprotein B and HDL cholesterol/apolipoprotein A1 ratios; there were no significant effects on the triglycerides. PMID- 1521981 TI - Nonoccupational determinants of blood lead concentrations in a general population. AB - We investigated the influence of various nonoccupational factors on blood lead levels (PbB) in a sample from the general population of southern Germany. Some 1703 men and 1661 women, aged 28-67 years, were examined in the first follow-up examination of the MONICA Augsburg cohort study in 1987-1988. Their mean PbB was 90 micrograms/l (SD:35.9) for men and 65 micrograms/l (26.4) for women. Only 5% of the men and 1% of all women exceeded a PbB level of 150 micrograms/l indicating low-level lead exposure in this population. Blood lead was significantly associated with haematocrit values (P < 0.001) and the shape of this association was curvilinear. Per gram of alcohol consumed, intake of beer had a lower impact on PbB than wine, presumably due to differential lead content in these alcoholic beverages. The alcohol-PbB associations were stronger for women than for men. The impact of smoking was generally moderate but again more prominent in women. In particular, the covariate adjusted odds ratios for women of childbearing age (28-47 years) to have PbB levels above 100 micrograms/l were 2.5 (95% confidence interval (CI): 1.3-4.7) for smoking versus non-smoking females, 2.6 (95% CI: 1.1-6.0) for women drinking up to 40 g alcohol/day compared to abstainers, and 8.9 (95% CI: 3.2-25.1) for those drinking more than 40 g alcohol/day. Other factors like age, body mass, rural place of residence, and education or job position, had only minor influences on PbB. We conclude that haematocrit values should always be considered as potential confounders in low level lead exposure research. High alcohol consumption and cigarette smoking are strongly related to elevated blood lead concentrations in the general population and may thereby convey additional health hazards such as impaired child development or blood pressure elevations. This deserves proper public health recognition [corrected]. PMID- 1521982 TI - Influence of individually estimated portion size data on the validity of a semiquantitative food frequency questionnaire. AB - Using data from a Danish dietary validity study, we evaluated the influence of including individually estimated portion size data on the validity of a semiquantitative food frequency questionnaire. A total of 144 subjects, aged 40 64 years were included. Correlation coefficients and classification of subjects into quintiles according to their intake of foods and nutrients were used to compare questionnaire data, with and without individually estimated portion size data, with data obtained by 2 x 7 days weighed diet records. For men, the mean correlation coefficient for food group comparisons was 0.47 when information about individually estimated portion sizes for food items that do not come in natural units was included in the analysis. Using a common average portion size reduced the mean correlation coefficient to 0.45. For women, similar changes were observed (0.36 to 0.35). For nutrients the mean values for the comparison changed from 0.51 to 0.49 and from 0.39 to 0.40 for men and women, respectively. For both men and women the classification into quintiles according to their intake of foods and nutrients showed only minor differences. We conclude that little extra information was gained by including individual portion size information for food items that do not come in natural units. This may reflect that portion sizes are of minor importance compared with frequencies or that the relevant individual portion sizes were not estimated correctly. PMID- 1521983 TI - Estimation of leprosy prevalence in Bago and Kawa townships using two-stage probability proportionate to size sampling technique. AB - Two surveys to estimate leprosy prevalence using two-stage probability proportionate to size sampling technique were conducted in Bago and Kawa townships. A total of 3519 and 3739 individuals were examined in each township. The two surveys were finished within 25 (Bago) and 30 (Kawa) working days at a cost of Kyats 10,000 (US $1500) for each survey. The estimated leprosy prevalence obtained in Bago was 9.95 per 1000 population (95% confidence interval (CI): 7.11 12.78) and in Kawa it was 12.04 per 1000 population (95% CI: 8.85-15.22). A total of 30 (Bago) and 34 (Kawa) new leprosy cases were detected in the two surveys. Grade I disability was seen to be 20% in Bago and 18.78% in Kawa, whereas grade II disability was 17.14% in Bago and 15.56% in Kawa. PMID- 1521984 TI - Assessing the extent of the HIV epidemic in Sweden, using information on the extent to which people who develop AIDS are already known to be HIV infected. AB - In Sweden, cases of both HIV infection and AIDS are registered. By looking at the extent to which people who develop AIDS are already known to be HIV-infected, we can assess the coverage of the HIV registration. It was found that virtually all those who were infected by injecting themselves with drugs, blood transfusions, blood products or congenitally were already known to be infected when AIDS developed. However, when homosexual or heterosexual transmission had occurred, 20.5% and 33.3% respectively of these cases were not previously known. Working with different assumptions regarding the development of the epidemic, we find that the true number of sexually infected people is roughly twice the number of registered HIV-infected people in these groups. Our estimate is that between 3300 and 6300 people were infected with HIV in Sweden up till the end of 1990. PMID- 1521986 TI - Predictors of poliomyelitis case confirmation at initial clinical evaluation: implications for poliomyelitis eradication in the Americas. AB - In 1985, the Pan American Health Organization adopted the goal of eradication of poliomyelitis from the Americas by 1990. Strategies to accomplish this included high vaccination coverage, aggressive outbreak control, and active surveillance for acute flaccid paralysis (AFP). Although the sensitivity of AFP surveillance for detecting paralytic poliomyelitis cases is high, studies have shown the specificity to be low. In 1990, 2497 notified cases of AFP were investigated in the Americas of which 2146 had stool specimens collected. However, only 18 were confirmed as poliomyelitis by isolation of wild poliovirus from stool specimens, 71 were classified as being compatible with poliomyelitis. Cases of AFP due to causes other than poliomyelitis result in extensive but unnecessary outbreak control measures. To predict, at initial clinical evaluation, the likelihood of future confirmation as a case of poliomyelitis, likelihood ratios (LR) were calculated for different combinations of clinical characteristics of AFP cases (249) from Mexico in 1989 and 1990. The best predictors in a child with AFP were proximal muscle involvement which progressed '4 days together with fever at onset of paralysis, and proximal and unilateral involvement with either fever at onset or paralysis which progressed '4 days. The odds would increase by 12 that the child would eventually be confirmed as poliomyelitis (19), based on a stool culture positive for wild poliovirus (95% confidence interval (CI) 2.6-55.9). A guide for use in the field is proposed whereby local health officials, often with little training in neurological evaluation, can predict at initial clinical examination the likelihood that an AFP case will subsequently be confirmed as poliomyelitis.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1521987 TI - Epidemiological features of an outbreak of diphtheria and its control with diphtheria toxoid immunization. AB - An outbreak of diphtheria primarily involving adults occurred in seven townships and one farm in Jiangling county, Hubei, China from September 1988 to January 1989. Of the 103 reported cases, 80 were aged over 16 years, and there were two deaths. One hundred cases were reported in Jingzhou and its surrounding townships, only three occurred in townships distant from Jingzhou. The incidence and case fatality rates were 11.54/100,000 and 1.94% respectively. Twenty-one strains of diphtheria bacillus were isolated from 68 patients. A special immunization programme using adsorbed diphtheria toxoid was conducted 1 month into the outbreak, following which the incidence declined rapidly. Five vaccinees subsequently developed diphtheria. PMID- 1521985 TI - A retrospective study of childhood mortality and spontaneous abortion in HIV-1 infected women in urban Malawi. AB - HIV infection in pregnant women has been shown to have an adverse effect on the fetus and newborn. We undertook this study to examine the adverse effect of maternal HIV-1 infection on two outcomes of the previous pregnancy, as reported by the women: childhood mortality under the age of 3 years and spontaneous abortion. Some 6605 consecutive women who presented to a large urban hospital in Malawi for antenatal care were interviewed and tested for HIV-1 antibody. Of these 4229 (64%) were multiparous and 833 (19.7%) were seropositive for HIV-1. A history of under-3 mortality of the previous pregnancy was more common in HIV-1 seropositive than HIV-1 seronegative women (35% versus 15%, P less than 0.001). In the previous pregnancy, death of infants and children under 3 years was 77 and 119 per 1000 respectively for HIV-1 seronegative mothers, but increased to 171 and 292 per 1000 in infants and children under 3 years for HIV-1 seropositive mothers. History of child mortality was independently associated with positive HIV-1 serology, positive syphilis serology, low socioeconomic status, young age and not having married. There was no correlation between history of child mortality and reported symptoms of HIV/AIDS by infected mothers, except for history of tuberculosis which was reported more often by mothers whose child had died (4% versus 1%, P less than 0.036).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1521988 TI - Risk factors for the transmission of diarrhoea in children: a case-control study in rural Malaysia. AB - In response to a recorded increasing incidence of diarrhoea in Tumpat District, Malaysia, a case-control study was performed to identify modifiable risk factors for the transmission of diarrhoea, in children aged 4-59 months. Ninety-eight pairs of children, matched on age and sex, were recruited prospectively from health centres. Exposure status was determined during a home visit. Interviewers were 'blinded' as to the disease status of each child. Odds ratios were measured through matched pair analysis and conditional logistic regression. Risk factors for diarrhoea identified were: reported--drinking of unboiled water, storage of cooked food before consumption and bottle feeding; and observations--animals inside the house and absence of washing water in latrines. Water quality, source of drinking water, reported hand washing behaviour, indiscriminate defecation by children, cup use and the absence of a functional latrine were not associated with diarrhoea. Nonsignificant associations were found for: accessibility of washing water source, type of water storage container and use of fly covers for food. PMID- 1521989 TI - The attributable fraction of the combined effect of two risk factors. PMID- 1521990 TI - Lack of positive bias of the confounding effect of risk factors estimated by marginal aetiological fractions. PMID- 1521991 TI - Utilization of research. PMID- 1521992 TI - Privacy, confidentiality and epidemiology: the Dutch ordeal. PMID- 1521993 TI - Comparative accuracy of implant impression procedures. AB - In this study, four impression procedures were assessed for accuracy in a laboratory model that simulated clinical practice. The accuracy of stone casts with brass implant analogs was measured against a standard framework. The fit of the framework on the casts was tested by manual and visual judgment and by microscopic measurement. The measurements supported the clinical judgments. When acrylic resin was used to splint transfer copings in an impression, all casts were acceptable and were more accurate than the best of the two other procedures, which did not use an acrylic resin splint. When an impression material was used to orient the transfer copings, the accuracy was better if undercut copings remained in the impression. When impressions were made by removing an impression from smooth transfer copings and replacing the copings in the impression, the majority of casts were unacceptable. PMID- 1521994 TI - Use of a collagen barrier to enhance healing in human periodontal furcation defects. AB - Guided tissue regeneration procedures are intended to selectively favor healing by the periodontal ligament tissues. However, in most studies of the efficacy of guided tissue regeneration, nonresorbable barriers and membranes have been used, necessitating their surgical removal after a time. The present study employed a resorbable collagen barrier to treat Class II function invasions. The results of this treatment were compared with the results of conventional therapy. For most clinical parameters, there was no statistically significant difference in the results of treatment with or without collagen membranes. Sites treated with a collagen barrier did exhibit statistically significant improvement in probing depth and horizontal osseous support; however, these findings cannot be attributed entirely to the placement of the collagen membrane. PMID- 1521995 TI - Reconstruction of bone on facial surfaces: a series of case reports. AB - To rebuild the damaged periodontium to its original form, it would be ideal not only to cover the denuded root surfaces with soft tissue, but also to reconstruct the cortical plate. This paper presents four cases in which osseous grafts and guided tissue regeneration, along with root surface conditioning, were used to encourage growth of new facial bone. Some degree of success was achieved in each case. PMID- 1521996 TI - Surgical reconstruction of the interdental papilla: case report. AB - Historically, periodontal treatment has been aimed more at the preservation and restoration of health to the periodontium than at the esthetic outcome of treatment. However, recent advances have enhanced the periodontist's ability to address esthetic concerns. To date, treatment of lost or collapsed interdental papilla has been largely unsuccessful. A case report is presented to demonstrate a technique by which a collapsed interdental papilla can be surgically reconstructed. The technique combines principles of Abram's roll technique for ridge augmentation with Evian's papilla preservation technique. PMID- 1521997 TI - Achieving ideal esthetics in osseointegrated prostheses. 1. Multiple units. AB - This article describes two new abutments that are intended to enhance the esthetics and function of the implant prosthesis while keeping it in harmony with the periodontium. Part 1 discusses the EsthetiCone, designed for use with multiple-unit restorations, which allows subgingival placement of porcelain for maximal esthetics. Unlike traditional abutments, the EsthetiCone is placed 4 to 6 weeks after the fixture is uncovered. Therefore, the size and type of abutment are chosen by the restorative dentist, rather than by the surgeon. Guidelines for abutment selection and placement are provided in this paper. PMID- 1521998 TI - "A rose is a rose is a rose". PMID- 1521999 TI - Enhancement of the damaged edentulous ridge to receive dental implants: a combination of allograft and the GORE-TEX membrane. AB - A severely damaged edentulous ridge frequently obviates the placement of dental implants or results in placing them at an angle that compromises the prosthetic restoration. This paper demonstrates the repair of severely resorbed edentulous ridges by a combination of bone allografting and the placement of a barrier membrane. The damaged edentulous ridge is treated first in this two-stage process. The implants are then installed at a second surgery. PMID- 1522000 TI - Parts and their roles in Hippocratic medicine. PMID- 1522001 TI - Total-body evaluation of a thorotrast patient. A tribute to Charles W. Mays, Jr. PMID- 1522002 TI - Comprehensive evaluation of a Thorotrast patient: an overview. AB - For several decades, thousands of people received Thorotrast during the course of angiography and other radiologic procedures. Eventually, as the hazards of this radioactive, radiographic contrast agent became apparent, research was initiated to further evaluate its associated adverse effects. In 1988 and 1989, Charles W. Mays, together with colleagues at a variety of sites, developed a detailed protocol for the comprehensive postmortem evaluation of one subject who had been administered Thorotrast 36 y previously. This case represents the first holistic approach to the analysis of Thorotrast in a whole body, simultaneously assembling clinical and autopsy findings with dosimetric, radiochemical, autoradiographic, and molecular evaluations. PMID- 1522003 TI - Portable 220Rn detector used to assess Thorotrast exposure. AB - Patients who are exposed by injection to the radiological contrast medium Thorotrast (232ThO2) had been considered by early researchers to be an unfortunate but important model of alpha-particle carcinogenesis in the lung as well as liver and bone marrow because they continuously exhale 220Rn, in the breath of Thorotrast patients and (as the first step to lung dosimetry) to investigate the relationship between exhaled 220Rn activity concentration (Bq L 1) and 232Th body burden. Results revealed that reliable estimation of 232Th burden by 220Rn measurement is possible because a fairly good correlation was obtained between 220Rn in the breath and the known quantity of 232Th in the body. Mean 220Rn activity concentration in the breath was 9.21 Bq L-1 g-1 of 232Th deposited in the liver and spleen. This value was very close to that published for German patients. Our data and those of other investigators indicate that apparent discrepancies in mean 220Rn activity concentration among previous studies was caused by using different 228Th:232Th activity ratios. PMID- 1522004 TI - Clinical consequences of Thorotrast in a long-term survivor. AB - Thorotrast, a colloidal suspension of 252Th dioxide, was widely used as a radiographic contrast medium for more than 25 y after its clinical practice introduction in 1930. Its excellence as a contrast medium was ultimately eclipsed by its long-term associated morbidities, and its use essentially ended by 1954. This case history presents the clinical events in the last 10 y of life in a patient injected with Thorotrast in 1953. This patient developed three previously described Thorotrast-associated morbidities: pneumococcus sepsis due to functional asplenia and reticuloendothelial system blockade, an enlarging Thorotrastoma (inflammatory mass) at the injection site, and a fatal blood dyscrasia. In addition, she developed three clinical syndromes where a Thorotrast association may exist. She suffered from severe spinal column osteoarthritis and vertebral collapse. An abnormal bone-density measurement implies the presence of radiodense radioactive thorium or its degradation products as potentially responsible. She had evidence of chronic immune system disregulation with immunoglobulin excess, auto antibodies, and cell-mediated immunity deficiency. This condition is similar to that found in patients infected with human immunodeficiency virus and may suggest a shared etiology in reticuloendothelial system damage. Lastly, she developed dense bilateral cataracts. This case history illustrates the temporal relationship of a variety of symptoms. Discussion is directed at review of previous data and support for new associations. PMID- 1522005 TI - Whole-body pathologic analysis of a patient with Thorotrast-induced myelodysplasia. AB - An autopsy was performed on a 72-y-old Caucasian female who had received a carotid artery injection of thorium dioxide in 1953. The body was dissected in such a manner as to provide for radiobiological evaluation as well as to determine histologically the distribution of Thorotrast in the tissues and its complications. Thorotrast was identified within the liver, spleen, lymph nodes, bone marrow, and surrounding the right carotid artery (the injection site). The cause of death was gastric hemorrhage complicating pancytopenia secondary to refractory anemia with excess of blasts (myelodysplastic syndrome). PMID- 1522006 TI - Alteration of the c-fms gene in a blood sample from a Thorotrast individual. AB - We analyzed six different tissue DNA samples from a leukemic individual who received an injection of Thorotrast for alterations in proto-oncogene or tumor suppressor gene structure. Our examination of the DNA indicated an alteration of the c-fms gene in the blood sample from this individual. This locus showed a deletion in which the 3' end of the deleted region maps between exons 11 and 12. In this particular case, the type of leukemia is unknown but myeloid leukemia is a neoplasm associated with individuals injected with Thorotrast. It is possible that the alteration in the c-fms gene of this individual is a consequence of the radiation exposure. No apparent alterations in the c-mos gene were observed in any of the tissues from the individual. This is in contrast to previous studies that described alterations in methylation patterns associated with the c-mos locus in radium-exposed individuals. A number of the individuals exposed to radium also had alterations of the retinoblastoma gene while no such alterations were observed in any tissue DNA samples from this Thorotrast case. It is possible that our inability to detect alterations of the c-mos and retinoblastoma gene may be attributable to the nature of alpha-emitting radionuclides or their distribution, or to the limited set of tissues available for analysis. PMID- 1522007 TI - A brief glance at the scientific legacy of Charles W. Mays, Jr. PMID- 1522008 TI - External gamma-ray counting of selected tissues from a Thorotrast patient. AB - Results of gamma-ray measurements of selected tissues from a patient who was injected with Thorotrast almost 36 y ago are reported. The purposes of this study were: 1) to determine the relative tissue distribution and activities of specific radionuclides in the 232Th decay chain, specifically 228Ra (as measured by 228Ac), 212Pb, and 224Ra (measured directly and as measured by 212Pb), and 2) to evaluate the level of radioactive disequilibrium among the daughter products. The spleen and liver had the highest concentrations of radioactivity. Bone also appears to be a long-term sink for 232Th daughter products based on estimates from a small portion of one rib. Larynx and esophagus contained measurable activity, which may have been due to their proximity to the "Thorotrastoma." Radioactivity in the remaining measured tissues were low, as expected. Secular equilibrium could be demonstrated in bone, pancreas, larynx, esophagus, and breast. Significant disequilibrium was observed for spleen, liver, kidney, and red blood cells. Radioactivity measurements reported here will be useful in estimating radiation doses to selected tissues. Such dose estimates are valuable in refining current risk estimates (e.g., liver) and in identifying tissues at risk for further epidemiologic studies. These results, while consistent with other published studies, should be interpreted with caution since measurements were made on only one patient. PMID- 1522009 TI - Microdistribution and microdosimetry of thorium deposited in the liver. AB - The distribution of thorium in the liver of a patient 36 y after injection with Thorotrast was examined with autoradiographic and scanning electron microscope backscatter image techniques. Autoradiographic examination of randomly selected histologic sections of the liver showed a total alpha activity calculated at 33.7 Bq g-1, with the highest concentration of alpha activity sequestered in subcapsular scare tissue. Subcapsular scare tissue received 4.8 cGy d-1 of alpha radiation, periportal areas were accumulating 1.4 cGy d-1, and the hepatic cord areas 0.09 cGy d-1 of alpha radiation at the time of death. The concentration of dose in periportal areas correlates with higher incidence of bile duct tumors (than hepatocellular carcinomas) found in patients exposed to Thorotrast. The backscatter technique was demonstrated as useful for identifying thorium in liver specimens. PMID- 1522010 TI - The distribution of Thorotrast in human bone marrow: a case report. AB - Samples of bone containing cellular and fatty bone marrow were removed at autopsy from the body of a woman who, following an automobile accident, had been injected with approximately 25 mL of the radiographic contrast medium Thorotrast. The woman survived for 36 y after the accident and died at age 72 y following bone marrow failure. The samples were analyzed to determine their thorium content by x ray fluorescence and by image analysis. In addition, Thorotrast was visualized in the different bones examined by light microscopy and by backscattered electron imaging with a scanning electron microscope. The results showed Thorotrast to be largely restricted to areas of cellular bone marrow. In such regions, Thorotrast was present throughout the marrow tissue and was also concentrated within cells that were commonly aggregated within focalized areas of the marrow. Overall the results suggest a rather uniform pattern of Thorotrast uptake by the red bone marrow at different skeletal sites. Significant deposits of Thorotrast were not found in fatty yellow marrow. We conclude that Thorotrast-derived risk estimates for human leukemia following high LET, alpha irradiation may be used for calculating the risks of alpha exposure, but with caution. PMID- 1522011 TI - Measurement of thorium isotopes and 228Ra in soft tissues and bones of a deceased Thorotrast patient. AB - The whole body of an individual injected with Thorotrast 36 y prior to her death was analyzed for 232Th, 228Ra, 228Th, and 230Th. Measurement of these isotopes in all tissues of the body will provide data necessary to caculate the radiation dose to individual tissues and to evaluate the risk potential associated with deposition of thorium and progeny in humans. The tissues were ashed, dissolved in acid, and the thorium isolated by ion exchange and electrodeposition. The 228Ra was determined by measuring the 0.991-MeV gamma rays associated with decay of the 228Ac daughter. It was estimated that almost all of the 232Th from the original injection was retained in the body, mostly in the tissues of the reticuloendothelial system. A total of 28 kBq (0.76 microCi) of 232Th was measured in the soft tissues and bones. The body also contained 13 kBq 228Ra, 12 kBq 228Th, and 3.9 kBq 230Th. A Thorotrastoma contained about 3.5% of the total activity. Excluding the Thorotrastoma, approximately 45% of all the activity (232Th, 228Ra, 228Th, and 230Th) was retained in the liver, 13% in the spleen, 2% in muscle, 1% in skin, slightly less than 1% in the respiratory tract, 4% in all other soft tissues, and 33% in the skeleton (bone and bone marrow). Sixty to 80% of the thorium activity in bones containing red marrow was located in the marrow. Bones containing yellow marrow had less than 40% of the thorium activity in the marrow. Highest concentrations were found in the hepatic and other abdominal lymph nodes, spleen, hilar lymph nodes, liver, trachea, and bone. Approximately 60% of the 228Ra formed from the decay of the 232Th had been excreted from the body. The 228Ra and 228Th were in approximate equilibrium throughout the body. PMID- 1522012 TI - Distribution and dosimetry of Thorotrast in USUR case 1001. AB - The distribution of radioactivity and the associated doses were evaluated postmortem for USUR Case 1001, a female who had been injected with Thorotrast some 36 y prior to death. The distribution was determined for four nuclides: 232Th and its decay products, 228Ra and 228Th; and 230Th, a contaminant associated with Thorotrast. More than 90% of the activity was associated with the reticuloendothelial system. Approximately 32% of the total activity was found in the total skeleton (mineral bone and bone marrow), which is somewhat higher than expected from the literature. The 44% found in the liver and 12% in the spleen were somewhat lower than expected. This difference may be attributable, in part, to the initial deposition as influenced by colloidal particle size and to the radiation-induced hyposplenism, splenic atrophy, and slight hepatic atrophy observed at autopsy. In addition, roughly 3% of the activity was found in the Thorotrastoma and surrounding carotid artery tissue. Estimated lifetime absorbed doses from the 232Th series were 15 Gy to the liver, 121 Gy to the spleen, 4 Gy to the skeleton, and 16 Gy to the Thorotrastoma. Comparable dose equivalents to these tissues are 300, 2420, 80, and 320 Sv, respectively, assuming a quality factor of 20 for alpha irradiation. PMID- 1522013 TI - Cancer risk following exposure to Thorotrast: overview in relation to a case report. AB - Radioactive measurements and histopathologic findings are described in a patient administered Thorotrast, a radiographic contrast agent, 36 y prior to death and compared with cancer risks noted in epidemiologic studies. This person [designated as U.S. Uranium Registry (USUR) Case 1001] had prearranged for donation of her body to the USUR and the National Cancer Institute for study. Elevated levels of radioactivity were noted in those organs in which excess cancers have been reported in epidemiologic surveys of Thorotrast-exposed subjects. Hepatic tissue in USUR Case 1001 was estimated to have received an average lifetime absorbed dose of 16.2 Gy, based on radiochemical analyses, consistent with the high risks for liver tumors reported in all studied populations. Thorotrast was present throughout the bone marrow of USUR Case 1001, who died secondary to complications of refractory anemia with excess blasts (RAEB). Elevated risks for acute myeloid leukemia have been noted in Thorotrast patients, and more recently, cases of RAEB and RAEB in transformation have been reported. The thorium decay series includes the bone-seeking radionuclides 224Ra and 228Ra, which have been associated with high risks for osteosarcomas, although the association between Thorotrast and bone cancer is not as convincing. The skeleton of USUR Case 1001, however, contained significant levels of radioactivity. Other tissues evaluated in USUR Case 1001 included lung, eye, kidney, and breast, which did not contain elevated levels of radioactivity. PMID- 1522014 TI - Shades of grey: radiopharmaceutical chemistry in the 1990s and beyond. PMID- 1522015 TI - Evaluation of reduction-mediated labelling of antibodies with technetium-99m. AB - Monoclonal antibodies can be labelled with technetium-99m by prereduction of the antibody with 2-mercaptoethanol, then reduction of pertechnetate with an aliquot of a stannous kit, resulting in greater than 97% labelling without the need for further purification. The present work shows that equally high labelling can be obtained with a variety of weak ligands and that the optimum quantity of stannous chloride is 2-4 micrograms. Although the label was stable to challenge with excess DTPA, cysteine was able to remove a portion of the label. We have also shown that this technique works with the IgG2a isotype in addition to the previously reported IgG1 isotype. This approach is simple, convenient and reproducible, and warrants further clinical evaluation. PMID- 1522016 TI - A convenient method for regional monoamine oxidase-A determination by [14C]clorgyline autoradiography. AB - The availability of clorgyline for regional monoamine oxidase-A (MAO-A) determination was examined using [14C]clorgyline in rat. [14C]Clorgyline was synthesized by the methylation reaction of N-desmethyl-clorgyline and [14C]methyliodide in dimethylformamide with high radiochemical yield. The MAO-A distribution map by autoradiography correlated with that by histochemical technique and its quantity was consistent with the calculated MAO-A amount based on previous reports. The combination of labeled clorgyline and autoradiographic technique will promise the quantitative measurement of regional MAO-A distribution. PMID- 1522017 TI - Tissue localization of [125I]triiodothyronine in the periorbital area of mice: a microautoradiographic study. AB - A significant retention of [125I]triiodothyronine ([125I]T3) in the retrobulbar orbital area of mice has been previously shown. The present study was initiated to determine tissue and intracellular localization of the thyroid hormone in the above area which is concerned in human Graves' disease of the thyroid. Male and female Balb C mice were intravenously injected with 0.1 mL of [125I]T3 (0.2 mCi/micrograms). At various time intervals (30 s-10 min) the animals were sacrificed, bled and periorbital tissues were isolated under a dissecting microscope. Three series of samples were prepared: (a) frozen samples for cryomicrotome sections, (b) samples fixed in 10% formaldehyde for paraffin embedded tissues and (c) samples fixed in paraformaldehyde (2%), glutaraldehyde (2%) and 0.1 M sodium cacodylate for embedding in Epon-Araldite-DDSA. Sections 5 microns and 400-600 A thick for light and electron microscopy, respectively, were coated with Ilford L4 emulsion and exposed for 9-21 days. Light microscope autoradiography demonstrated that [125I]T3 injected intravenously is rapidly transported in the cells of fat tissue of the peribulbar orbital area and tissues with glandular or muscular function: the hormone showed a high affinity for the intra- and extraorbital lacrymal gland cells, the cells of the Harder's gland, those of the sebaceous and meibomian glands of the eye-lids, as well as for local muscular structures. Electron microscope autoradiography showed that radioactivity is already localized inside the cells 30 s after the i.v. injection of [125I]T3 and it is distributed throughout the cytoplasm, with a higher concentration in the vesicles of the Harder's gland cells (rich in lipids and porphyrin), in the endoplasmic reticulum and the mitochondria of the lacrymal glands. 10 min after injection, a shifting of the radioactivity towards the nucleus area was observed. In conclusion, after in vivo injection, the thyroid hormone rapidly penetrates the cells of fat glandular and muscular tissues in the orbital area. Intracellularly, the affinity of the hormone for the secretory vesicles, rough endoplasmic reticulum, mitochondria and nucleus suggest that T3 could play a role in secretory and metabolic functions of the tissues in the retrobulbar orbital area. PMID- 1522018 TI - Potential organ or tumor imaging agents. 32. A triglyceride ester of p-iodophenyl pentadecanoic acid as a potential hepatic imaging agent. AB - A triglyceride analog, glycerol-2-palmitoyl-1,3-di-15-(p iodophenyl)pentadecanoate (DPPG) was synthesized and radiolabeled for evaluation as a potential functional liver scintigraphic agent. Uptake of DPPG was compared in normal, diabetic, tumor-bearing and heparin pretreated rats, revealing differences in uptake and clearance of radioactivity, correlating with hepatic lipase activity of these groups. Similar results were observed by gamma-camera scintigraphy. Comparing the uptake of DPPG with that of its fatty acid component, 15-(p-iodophenyl)pentadecanoic acid (IPPA), revealed that the peak uptake of IPPA in the liver was about half that of DPPG. Based upon these findings, DPPG warrants further study as a hepatic radiodiagnostic agent. PMID- 1522019 TI - Internal-surface reversed-phase chromatography for plasma metabolite analysis of radiopharmaceuticals. AB - The use of internal-surface reversed-phase (ISRP) chromatography of unprocessed plasma samples was investigated as an alternative method of quantitation of the arterial plasma metabolite time course of [18F]N-methylspiperone. The ISRP method was directly compared to standard solid phase extraction/HPLC (SPE/HPLC) methods currently in wide use. Results indicate that: (1) the ISRP method is rapid and minimizes sample preparation; (2) recovery of radioactivity from the ISRP column is greater than 90%; (3) no radioactivity remains associated with chromatographically size excluded proteins and (4) the quantitative results are well correlated with conventional SPE/HPLC methods. PMID- 1522020 TI - Tumor localization and radioimaging with mixtures of radioiodinated monoclonal antibodies directed to different colon cancer associated antigens. AB - After demonstrating enhanced tumor cell binding with a mixture of monoclonal antibodies (MAbs) in vitro, biodistribution and immunoscintigraphy studies with 3 radioiodinated anti-colon cancer MAbs and a non-specific control MAb (MOPC) were conducted in a human colon cancer (GW-39)-hamster model system. Each of the specific MAbs, but not MOPC, demonstrated extensive tumor binding and in scintigrams affected visualization of all large tumors (greater than 0.85 g) over background. Using single MAbs, few small tumors (0.19-0.50 g) were defined above background (0-29%). However, with combinations of these specific MAbs small tumors were more frequently defined in scintigrams (43-67%). Radioimages using higher doses of MAbs and small, younger tumors more clearly demonstrated the superiority of a MAb mixture. These results confirmed that combinations of MAbs to different antigens can detect smaller tumors with better tumor localization when compared to component MAbs used singly. This study supports the concept that tumor targeting and detection may be enhanced with appropriate mixtures of MAbs. PMID- 1522021 TI - Labeling and stability of radiolabeled antibody fragments by a direct 99mTc labeling method. AB - The in vitro labeling and stability of 99mTc-labeled antibody Fab' fragments prepared by a direct labeling technique were evaluated. Eight antibody fragments derived from murine IgG1 (N = 5), IgG2a (N = 2) and IgG3 (N = 1) isotypes were labeled with a preformed 99mTc-D-glucarate complex. No loss of radioactivity incorporation was observed for all the 99mTc-labeled antibody fragments after 24 h incubation at 37 degrees C. The 99mTc-labeled antibody fragments (IgG1, N = 2; IgG2a, N = 2; IgG3, N = 1) were stable upon challenge with DTPA, EDTA or acidic pH. Furthermore, using the affinity chromatography technique, two of the 99mTc labeled antibody fragments displayed no loss of immunoreactivity after prolonged incubation in phosphate buffer up to 24 h at 37 degrees C. The bonding between 99mTc and antibody fragments was elucidated by challenging with a diamide ditholate (N2S2) compound. The Fab' with IgG2a isotype displayed tighter binding to 99mTc in comparison to the Fab' from IgG1 and IgG3 isotype in N2S2 challenge and incubation with human plasma. The in vivo biodistribution of five 99mTc labeled fragments were evaluated in normal mice. In conclusion, the direct labeling method allows stable 99mTc labeling of antibody fragments from three of the major murine isotypes. PMID- 1522022 TI - Synthesis and evaluation of technetium-99m monocationic mixed ligand complexes of phenyl substituted/condensed tetradentate Schiff's bases and trimethylphosphine. AB - Tc-99m monocationic mixed ligand complexes of phenyl substituted/condensed Schiff's bases, N,N'-ethylene-bis-(benzoylacetone imine) (Lb) or N,N'-ethylene bis-(salicylaldehyde imine) (Lc) or N,N'-ethylene-bis-(2-hydroxyacetophenone imine) (Ld) and trimethylphosphine were synthesized to determine the influence of the presence of a phenyl group in these tracers on their heart uptake in rats. A new formulation procedure using aq. beta-hydroxypropylcyclodextrin (HPB) solution was developed for intravenous administration of nonpolar 99mTc complexes. Comparison of biodistribution data for the reference 99mTc complex from N,N' ethylene-bis-(acetylacetone imine) and trimethylphosphine using HPB formulation and alternate formulation (0.9% saline) showed the same results. Biodistribution of the title 99mTc complexes, [99mTc Lb (PMe3)2]+, [99mTc Lc (PMe3)2]+ and [99mTc Ld (PMe3)2]+ showed heart-to-blood activity ratios of 1.7, 2.1 and 1.7, respectively, at 15 min post-injection in rats. PMID- 1522023 TI - Design of compounds having enhanced tumour uptake, using serum albumin as a carrier--Part II. In vivo studies. AB - In the present in vivo study the uptake kinetics of radioiodinated albumin were determined in normal organs, and tumours of rats using sequential scintigraphy. Rat serum (RSA) was radioiodinated either directly at a tyrosine residue (d-RSA), or indirectly at a residualizing marker tagged to the albumin (rm-RSA). These labelling procedures did not alter the kinetics of labelled albumin, as shown by blood disappearance curves. Directly labelled albumin was shown to have tumour uptake. Residualizing markers like tyramine-cellobiose (TCB), tyramine deoxysorbitol (TDS) and aminonaphthaltyrimide-deoxysorbitol (ANTDS) are metabolically inert. After the intracellular degradation of the albumin carrier the TCB-, TDS- and ATNDS-residues accumulate in the lysosomes, particularly those of tumour cells. It was able to be demonstrated that residualizing-marker tagged albumin-bound radioactivity was five times higher after 72 h than the tumour radioactivity after use of directly labelled RSA. These data found support when whole-body retention of directly labelled RSA, and residualizing marker-RSAs, were determined. After 72 h, 60% of 131I bound to RSA directly had been excreted, compared to only 25% of the activity attached indirectly to RSA with a residualizing marker. Whole-body autoradiography of rats injected with directly labelled RSA, or residualizing marker-RSA, support these results. Most of the radioactivity of directly labelled RSA was excreted within 24 h, whereas labelled residualizing marker-RSAs were also stored in tumour and liver tissue. ANTDS bound to RSA allows fluorescence microscopy. Cryosections of tumours from rats preinjected 10 min and 24 h with ANTDS-RSA before dissection, demonstrated that the fluorescence is localized on and in tumour cells. This indicates that cellular uptake of the marker takes place. Fluorescence was not observed in muscle tissue. This appears to suggest that the albumin uptake is greater in tumours than in normal tissue, and that it is metabolized in the tumour cells. PMID- 1522024 TI - Subcellular distribution of tissue radiocopper following intravenous administration of 67Cu-labeled Cu-PTSM. AB - The subcellular distribution of radiocopper in the brain and liver of rats has been determined following i.v. administration of Cu-PTSM, pyruvaldehyde bis(N4 methylthiosemicarbazonato)copper(II), labeled with copper-67. Homogenized tissue samples were separated by differential centrifugation into four subcellular fractions: (I) cell membrane + nuclei; (II) mitochondria; (III) microsomes; and (IV) cell cytosol. Upon sacrifice at 10 min post-Cu-PTSM injection, brain fractions, I, II, III and IV contain 35 +/- 12, 11 +/- 3, 2.8 +/- 1.3 and 51 +/- 7% of brain activity, respectively (n = 4). In animals sacrificed 24 h post injection the subcellular fractions of brain tissue show little change from the radiocopper distribution seen at 10 min post-injection, although the mitochondrial fraction may contain slightly more tracer and the cytosolic fraction slightly less (I, 40 +/- 10%; II, 18 +/- 5%; III, 3.4 +/- 1.5%; and IV, 38 +/- 5%; n = 5). Subcellular fractions I, II, III and IV of liver contain 25 +/ 5, 12 +/- 3, 17 +/- 4 and 46 +/- 6% of 67Cu tracer in animals sacrificed 10 min post-Cu-PTSM injection. An identical subcellular distribution of 67Cu, was found in the liver following i.v. administration of ionic radiocopper (as Cu-citrate). The liver and brain cytosolic fractions at 10 min post-injection were further separated by Sephadex column chromatography. In liver cytosol, three different radiocopper components with molecular weights of about 140,000, 41,000-46,000 and 10,000-16,000 Da were found. In the brain supernatant fraction, most of the radiocopper was bound to a single low molecular weight cytosolic component (14,000-16,000 Da).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1522025 TI - A convenient synthesis of N-succinimidyl-3-iodo-[125I]benzoate, a reagent for protein iodination. AB - A convenient procedure has been developed for the synthesis of N-succinimidyl-3 iodo-[125I]benzoate. The procedure involved the synthesis of chloromercuribenzoic acid, its esterification with N-hydroxysuccinimide (NHS) and exchanging the mercury moiety with radioactive iodine in the presence of an oxidant. The obtained product was attached to human serum albumin and its stability was compared with Chloramine-T (Ch-T) radioiodinated protein. The results indicated that the reagent-radiolabeled protein was stable for longer periods and the deiodination rate was significantly lower. PMID- 1522026 TI - Utility of technetium-t-butyl isonitrile (99mTc-TBI) myocardial imaging in coronary artery disease. AB - 99mTc-t-butyl isonitrile is a useful agent for myocardial perfusion imaging. The superior physical advantages of technetium over 201thallium make larger doses possible for imaging. Accumulation in the myocardium is unidirectional in that once attached it does not leave the myocardium and hence two separate injections are needed for rest and stress imaging. High liver uptake frequently conceals the inferior wall and high early uptakes make immediate post-injection imaging almost impossible at least up to 45-60 min. This agent, however, was seen to accurately identify under-perfused areas and distinguish between ischaemia and infarct in our patients. Agreement with 201Tl and with GBP study of regional wall motion was excellent. While its individual sensitivity and specificity are quite high at 82.6 and 90.9%, in combined GBP studies the sensitivity rose to 93.4%. It is concluded that Tc-TBI is a valuable agent for myocardial perfusion scintigraphy, especially in a developing country like India where Tc-MIBI cannot be routinely used, since it is expensive, and where regular supplies of 201Tl are also not always feasible due to the high cost of importing. 99mTc-TBI can be made cheaply here and in a select population, notably in those with left anterior descending and circumflex coronary artery disease, it can provide valuable information. PMID- 1522027 TI - Differences in mental task performance and slow potential shifts in subjects differing in cortisol level. AB - Hormones of the pituitary-adrenocortical axis (e.g., cortisol) are involved in the regulation of brain function. This study was aimed to clarify whether individual differences in baselines of cortisol are related to differences in heart rate (HR), slow brain potential shifts (SPS), performance data and personality. 17 males were instructed to solve 120 arithmetical tasks under time stress conditions. They could obtain monetary bonuses according to the accuracy of their task performance. This test condition was compared to a control condition. To determine the plasma level of cortisol by radioimmunoassays four blood samples were collected during the session. Baselines were estimated twice. A clustering procedure with respect to all cortisol levels resulted in a group of high responders (HC, n = 9) and a group of low responders (LC, n = 8). The HR was significantly higher in the HC group. The SPS of the LC group were characterized by a larger P300 elicited by the task followed by a steep negative slow wave (NSW) as compared to the HC group. LC subjects also showed a higher NSW before feedback presentation. The LC group solved the tasks faster and obtained more than twice the reward than the other group. They scored higher in achievement motivation and also reported increased 'Social Acceptance' and decreased 'Tiredness'. In sum, the results suggest a more efficient regulation of the arousal level of the LC group in contrast to the HC group as far as reflected in the parameters analysed. PMID- 1522029 TI - Effect of phenytoin on the human neuronal activity and depth event-related potential in emotional task. AB - Neuronal activity and depth ERP were recorded from cortical areas and subcortical nuclei of three patients with diagnostic and/or therapeutic intracerebral electrodes while they were performing emotional task before and after phenytoin administration. Phenytoin acted as a bioelectrical modulator, in some cases increasing and in some cases decreasing the mean background neuronal firing level. In some few cases the more specific task-related effect of phenytoin was found as an inversion of the inhibitory response into the excitatory one in trials evoking negative emotions. PMID- 1522028 TI - Learning induces changes in the central cholinergic system of the rat in a sexually dimorphic pattern. AB - The involvement of the central cholinergic system in learning and the possible sexual dimorphism in related brain responses were investigated. Rats were exposed to different environmental conditions and to active avoidance learning. The resulting changes were studied using the following approaches: muscarinic receptor binding (MRB), acetylcholinesterase (AChE) and choline acetyltransferase (CAT) activities. The statistical evaluation of the data reveal that learning induces changes, especially in the postsynaptic component of the central cholinergic system, which shows some sexual dimorphism, and that males and females respond with different levels of increased cholinergic activity to informal and associative learning. PMID- 1522030 TI - Decrements in heart rate variability during memory search. AB - Heart-rate variability (HRV) was recorded from subjects as they rested or performed two memory-search tasks with different memory-set sizes. Results indicated that all the estimates of HRV were considerably greater during resting periods than during the task but only the mid-frequency band (0.1 Hz component) reflected the changes in memory-set size by a more pronounced decrement with the higher load. Subjective mental-effort ratings collected for the task periods also reflected the different memory loadings but did not correlate with HRV measures. PMID- 1522031 TI - Effect of task decision on P300. AB - Previous studies have shown that the structure of an experimental task may modulate P300 (P3) responsiveness to task-related test stimuli. In this study, four tasks were compared to study possible effects of decision type on P3s to rare and frequent visual word stimuli. One or three oddballs were designated in two separate experiments. Subjects in each experiment viewed randomized and repeated presentations of nine 5- to 8-letter words, and performed each of four target detection and choice discrimination tasks: (1) silent counting of oddball(s), (2) button-press to oddball(s), (3) choice response ('yes' or 'no') to oddball(s) and frequents, and (4) choice button-press to oddball(s) and frequents. Although oddball stimuli elicited characteristic 'target' P3s over the parietal scalp, there was no significant effect of task type on the oddball evoked P3. Frequents tended to elicit larger P3s in the choice discrimination tasks (yes/no, go/go) than in target-detection tasks (counting, go/no-go), indicating a selective effect of decision type on P3s to frequent-category events. PMID- 1522032 TI - Computer determination of systolic time intervals based on impedance cardiography. AB - A computerized system has been developed based on impedance cardiography for processing systolic time intervals (STI) in psychophysiological experiments. The conventional method of STI determination is based on transducing three signals: electrocardiogram, phonocardiogram and pulse tracing (carotid pulse). Because of its negligible pulse transmission time the first derivative impedance cardiogram (dZ/dt) is more reliable than other pulse signals. Since the sharply demarcated points of the dZ/dt waveform occur simultaneously with the cardiac events the dZ/dt makes phonocardiogram processing unnecessary. Computer algorithms for STI assessment are based on processing two signals: the ECG and dZ/dt. The pre ejection period (PEP), the left ventricular ejection time (LVET) and electromechanical systole (QS2) are derived by recognizing the B and X points on the dZ/dt signal as the endpoints of PEP and LVET respectively. X point identification consists of two steps: (i) the estimation of the QS2 based on the regression relationship between QS2 and heart rate (HR) and (ii) a filtering procedure for exact localization of the X point. The B point is determined by calculating the curvature function of the dZ/dt and employing a clustering procedure. The accuracy and reliability of the software were tested by processing data from 40 subjects under stress condition (cold pressor and mental arithmetic). PMID- 1522033 TI - Rare events and the CNV--the oddball CNV. AB - Event-related brain potentials (ERPs), such as Nd and P300, change as a function of the proportion of time if a rare, significant, stimulus occurs. This 'oddball' paradigm has had a significant influence on the interpretation of ERPs in terms of the psychological and information-processing functions they reflect. Interpretations of transient components have differed considerably from that of the sustained potential known as the Contingent negative Variation (CNV), the latter appearing to reflect proactive rather than reactive brain processes. However, experiments in monkeys indicated that the CNV was also sensitive to the oddball effect. The purpose of this experiment was to replicate that finding in humans. The CNVs and P300s of five male and five female college students were studied under three conditions involving different proportions of two types of warning stimuli in a cued reaction time task (paired tone and light). The proportions of one of the warning stimuli, with respect to the total number of trials, were 0.10, 0.30 and 0.50. P300s were larger when elicited by rare warning tones only in the 0.10 condition with maximum P300 amplitude at the parietal site. CNVs at frontal and central areas were larger when the warning cue was the rare event, but there was no effect at the parietal site. These findings may require a rethinking of specific information processing interpretations of other endogenous ERPs, although the results also indicate that the 'oddball' effect on the P300 and CNV was distinctive in terms of scalp distributions and sensitivity to the manipulation. PMID- 1522034 TI - A comparison of cardiovascular and autonomic adjustments to three types of cold stimulation tasks. AB - Two types of 'cold pressor' tasks are used frequently in research settings: immersing the hand or foot in ice water, and applying an icebag to the forehead. Both tasks have commonly been selected as 'alpha-adrenergic' tasks due to expected increases in blood pressure and peripheral resistance. However, the forehead cooling task has been used by others to produce increased vagal tone due to the elicitation of the 'diving reflex' and subsequent bradycardia. This differs from the prototypical increase in heart rate during hand immersion. The present study directly compared the cardiovascular adjustments of hand immersion and forehead stimulation. As stimulation of the trigeminal nerve is thought to increase vagal activity during forehead cooling, a third condition in which most of the face was covered with an icebag was included to ostensibly stimulate more of the trigeminal. 18 males had counterbalanced exposures to hand immersion, forehead cooling, and facial cooling for 90 s each. Cardiovascular variables derived from impedance cardiography and the ECG were measured. Respiration was paced at 14 breaths/min to facilitate comparisons of respiratory sinus arrhythmia across conditions. No differences among baseline or tasks were found for respiratory rate or cardiac output. The pattern of results for hand immersion was that of increased heart rate with moderate blood pressure increases. In contrast, the forehead and facial cooling tasks elicited small heart rate decreases with little change in blood pressure. Facial cooling elicited significantly more vagal activation than hand cooling as indexed by respiratory sinus arrhythmia. The patterns of response for facial and forehead cooling were almost identical. Probable reasons for the lack of significant blood pressure responses during the facial and forehead cooling are discussed. PMID- 1522035 TI - Temporal relationships between changes in phantom limb pain intensity and changes in surface electromyogram of the residual limb. AB - Previous studies of relationships between surface EMG of the residual limb and phantom pain have not shown which changed first. Thus, predictive relationships could not be demonstrated. 24 male (20) and female (4) amputees between the ages of 33 and 71 who reported either burning (3), cramping (8), shocking-shooting stabbing (6), or a combination of these descriptions of phantom pain (7) participated in one or two recording sessions. Raw surface EMG from the major muscles of the residual limb was recorded while subjects activated an event marker to indicate changes in pain. All eight subjects with cramping phantom pain reported changes in pain after the recording showed sharply demarcated increases in EMG. Subjects reporting either shocking-shooting or burning pain did not show any consistent relationships between EMG and pain. Three of the four subjects reporting experiencing both shocking-shooting and cramping phantom pain simultaneously during recordings showed changes in EMG preceding changes in pain. Sensations of cramping phantom pain were preceded by increases in muscle tension in the residual limb in almost every instance for each of our subjects showing changes in cramping phantom pain. Thus, changes in muscle tension in the residual limb are likely to either be causes or close intermediaries for the cause of cramping phantom pain but not necessarily of other common descriptors. PMID- 1522036 TI - Paranoid-nonparanoid differences--psychophysiological parallels. AB - It was predicted that the psychological differences between paranoids and nonparanoids would be parallelled by differences in psychophysiological responses to stimuli varying along both informational and motivational dimensions. Skin conductance and heart rate responses to stimuli in a guessing task were measured in a group of paranoid patients and compared with those from non-paranoid and non patient controls. A group of nonschizophrenic patients on phenothiazine medication served as drug-matched controls. Skin conductance level, response frequency and amplitude data are reported; heart rate response changes were examined by means of times series analysis and reported as first and second deceleration and first and second acceleration components. It was predicted that paranoid patients would show a greater increase in skin conductance measures with cognitive demand, and an increase in acceleratory components of the heart rate to increases in motivational variables. The normal pattern of greater electrodermal responding to the negative stimuli than the positive, and greater heart rate acceleration to the positive stimuli but not the negative (Fowles, 1980) was predicted to be reversed in schizophrenic patients, and possibly more marked in paranoids. Cognitive manipulations showed the predicted increase in electrodermal and heart rate responding in normal controls. The paranoid subjects showed a similar increase as a function of task demands, but there was no significant difference between the other groups. Motivational manipulations produced increased skin conductance responding and increases in heart rate acceleration components in normal controls, this was not parallelled in the patient groups. All subject groups failed to show greater electrodermal activity to negative than to positive stimuli. Normal controls showed significant heart rate acceleration to positive as compared to negative stimuli, this pattern was reversed in paranoid patients. PMID- 1522037 TI - Does the N100 evoked potential really habituate? Evidence from a paradigm appropriate to a clinical setting. AB - This study examined the N100 component of the event related potential in a habituation paradigm with short interstimulus intervals. The paradigm was designed to be relatively brief in duration (approx. 4 min for each of two conditions), so that it could be used for clinical populations with cognitive dysfunction, in which compliance may be a problem with long paradigms. Two conditions - Ignore and Attend - were employed with normal subjects. In each condition, 15 stimulus trains, each consisting of 10 innocuous tones, were presented. The eighth tone was a change stimulus. There was a fixed interstimulus interval of 1.1 s and an inter-train interval of 5 s. From the perspective of traditional Orienting Response theory, evidence was sought for within-train habituation in terms of diminished N100 amplitude to repeated stimuli, response recovery to the change stimulus, and dishabituation of the response to the following standard stimuli. Habituation was suggested by significant decreases of approx. 50% with stimulus repetition, and response recovery to the change stimulus in both conditions. However, there was no evidence of dishabituation following the change stimulus. These results confirm that N100 fails to meet the formal requirements of response habituation, suggesting instead that it may index an earlier process than the Orienting Response. PMID- 1522038 TI - Establishment and characterization of a SV40 T-antigen immortalized human bronchial epithelial cell line. PMID- 1522039 TI - Growth characteristics of a permanent human endothelial cell line. PMID- 1522040 TI - Long-term culture of normal human kidney glomerular cells. PMID- 1522041 TI - Hair growth in vitro from histocultured skin. PMID- 1522042 TI - Structural biology of epithelial tissue in histophysiologic gradient culture. AB - Epithelial cells proliferate, forming organized tissues, when positioned in the lumen of a thin-walled, transparent, elongated cylindrical, cystlike culture chamber. The closed chamber, 2.5 mm in diameter and 25 mm long, bathed in medium, incubated with continuous gentle agitation, enables the inoculum to exchange metabolites including oxygen by diffusion across the thin, nylon filament reinforced collagen membrane wall of the chamber. After periods of culture of a week or more, using inocula derived from urothelium, the inner surface of the cystic chamber is lined by a stratified epithelium. Proliferation of cells is seen in the basal zone, which is attached to the collagen substrate. The development of the model is briefly described. Some of the applications of the procedure are illustrated using cell lines, chick embryo tissues, and clinical tissues. Implications of the procedure are considered for studying categories of tissue biology, e.g., problems of aging, neoplasia, and toxicology. PMID- 1522043 TI - Establishment of primary cultures of rat and human parotid epithelial cells for transfection experiments. AB - The molecular mechanisms that regulate the synthesis of salivary proteins are unknown. The paucity of homogeneous cell populations of parotid acinar cells has become a limiting factor for such a study. Therefore, the establishment of immortalized clones of acinar cells is essential. This study has established primary cultures of rat and human parotid epithelial cells that are suitable for transfection with plasmid vectors, pSV2, pSV3, and pSV5 to generate immortalized cells in vitro. Among various techniques used, the rat and human parotid tissue or cellular clumps when restrained in chicken plasma clot allowed the outgrowth of epithelial cells that maintained epithelial cell morphology for over 4 wk. However, the initial growth requirements for rat and human parotid cells were different. The presence of 10% heat inactivated fetal bovine serum in supplemented MCDB-LB medium was essential for the outgrowth of rat parotid epithelial cells, but this was not needed for the outgrowth of human parotid epithelial cells. The growth of both human and rat parotid epithelial cells can be maintained in serum-free supplemented MCDB-LB. These primary cultures contained amylase-producing cells as demonstrated by immunofluorescent technique, and they were transfected with pSV2, pSV3, and pSV5 using primarily the calcium phosphate-DNA co-precipitation technique. After initial extensive cell death, many cells with epithelial cell morphology survived. PMID- 1522044 TI - Interaction of mouse ectoplacental cone trophoblast and uterine decidua in vitro. AB - During the peri-implantation stages of mouse development, the secondary trophoblast invades into the uterine decidua. This uniquely controlled invasive process results in the formation of the placenta. We have analyzed this process in vitro using cultures of decidua and microdissected ectoplacental cones from Day 7 embryos. The results showed that the interaction between these two cell types is comparable to that seen in vivo. Morphologically, the decidua maintained close contact with the spreading trophoblast, limiting its invasion and producing a multilayered trophoblast outgrowth. Attachment to the decidua was not mediated through cell-matrix binding, but the subsequent invasion into the decidua was dependent on normal matrix interactions. Secretion of proteinases by the trophoblast also seemed to be a requirement for successful invasion, but not attachment. PMID- 1522045 TI - An in vitro model for cell-cell interactions. AB - Heterotypic cell-cell interactions appear to be involved in the control of development and function in a wide variety of tissues. In the vasculature, endothelial cells and mural cells (smooth muscle cells or pericytes) make frequent contacts, suggesting a role for intercellular interactions in the regulation of vascular growth and function. We have previously grown endothelial cells and mural cells together in mixed cultures and found that heterocellular contact led to endothelial growth inhibition. However, this mixed culture system does not lend itself to the examination of the effects of contact on the phenotype of the individual cell types. We have therefore developed a co-culture system in which cells can be co-cultured across a porous membrane, permitting intercellular contact while maintaining pure cell populations. Co-culture of endothelial cells and smooth muscle cells across membranes with pore sizes of 0.02, 0.4, 0.6, and 0.8 microns maintained the two cell types as homogeneous populations, whereas smooth muscle cells migrated across the membrane through pores of 2.0 microns. Vascular cell co-culture across membranes with 0.8-microns pores resulted in the inhibition of endothelial cell proliferation and the generation of conditioned media which inhibited endothelial cell growth The arrangement of the cells in this co-culture system mimics the in vivo orientation of vascular cells in which mural cells are separated from the abluminal surface of the endothelium by a fenestrated internal elastic lamina or basement membrane. Because this co-culture system maintains separable populations of cells in contact or close proximity allowing for biochemical and molecular analyses of pure populations, it should prove useful for the study of cell-cell interactions in a variety of systems. PMID- 1522046 TI - Purine nucleosides and nucleotides stimulate proliferation of a wide range of cell types. AB - Presumptive astrocytes isolated from 10-day white Leghorn chick embryos, Factor VIII-positive human brain capillary endothelial cells, meningeal fibroblasts from 10-day chick embryos, Swiss mouse 3T3 cells, and human astrocytoma cell lines, SKMG-1 and U373, were rendered quiescent when placed in culture medium that contained 0 or 0.2% serum for 48 h; their proliferation was markedly reduced and they incorporated [3H]thymidine at a low rate. [3H]Thymidine incorporation and cell proliferation were induced in all types of cells by addition of guanosine, GMP, GDP, GTP, and to a lesser extent, adenosine, AMP, ADP or ATP to the culture medium. The stimulation of proliferation by adenosine and guanosine was abolished by 1,3-dipropyl-7-methylxanthine (DPMX), an adenosine A2 receptor antagonist, but not by 1,3-dipropyl-8-(2-amino-4-chorophenyl)xanthine (PACPX), an A1 antagonist. Stimulation of proliferation by the nucleotides was not abolished by either DPMX or PACPX. The P2 receptor agonists, alpha, beta-methyleneATP and 2-methylthioATP, also stimulated [3H]thymidine incorporation into the cells with peak activity at approximately 3.5 and 0.03 nM, respectively. These data imply that adenosine and guanosine stimulate proliferation of these cell types through activation of an adenosine A2 receptor, and the stimulation of cell proliferation by the nucleotides may be due to the activation of purinergic P2y receptors. As the primary cultures grew older their growth rate slowed. The capacity of the purine nucleosides and nucleotides to stimulate their growth diminished concomitantly. The 3T3 cells showed neither decreased growth with increased passages nor reduced response to the purines. In contrast, although the doubling time of the immortalized human astrocytoma cell lines SKMG-1 and U373 remained constant, the responsiveness to purinergic stimulation of the U373 cells decreased but that of the SKMG-1 did not. These data are compatible with a decrease in the number, or the ligand-binding affinity of the purinergic receptors, or a decreased coupling of purinergic receptors to intracellular mediators in primary cells aged in tissue culture. PMID- 1522047 TI - Growth, morphologic, and invasive characteristics of early and late passages of a human endometrial carcinoma cell line (RL95-2). AB - Two in vitro passages of a human endometrial adenocarcinoma continuous cell line (RL95-2), an early (subcultured less than 30 times) and a late passage (subcultured greater than 200 times) have provided an interesting model to study the growth, morphologic, and invasive properties of endometrial tumors. The early passage, which has been shown to be estrogen-receptor positive, has characteristics closely resembling a primary tumor, whereas the estrogen receptor negative late passage exhibits several features of the metastatic phenotype. Compared to the early passage cells, the late passage cells were less serum dependent, formed foci, demonstrated a faster rate of growth (due to their shorter doubling times), and attained higher saturation densities. The late passage cells also displayed an altered morphology which was accompanied by alterations in the distribution of F-actin. Even though early and late passages showed similar invasive potential in an in vitro invasion assay, the late passage cells, by virtue of their several transformed characteristics, maintain distinctive properties compared with their early passage counterparts. PMID- 1522048 TI - Application of highly polymorphic DNA markers to the identification of HeLa cell sublines. AB - Polymorphic DNA markers were used to identify eight sublines derived from HeLa. Using five highly polymorphic minisatellite DNA probes, these cell lines were distinguished and classified into six groups by Southern blot analysis. Polymorphic DNA markers, therefore, can provide a useful tool for monitoring genetic changes of a cell line during culture and for distinguishing sublines derived from the same origin. PMID- 1522049 TI - Replication of Autographa californica baculovirus (AcMNPV) in a coleopteran cell line. AB - A coleopteran cell line (AGE) derived from the cotton boll weevil Anthonomus grandis supported replication of Autographa californica multiple nuclear polyhedrosis virus (AcMNPV). The titer of extracellular virus (ECV) and the number of occlusion bodies (OB) produced in AGE cells were approximately equal to those produced by a Trichoplusia ni cell line (TN-CL1), and the OB produced by both cell lines were equally infectious for T. ni larvae. The identity of the AGE cell line was established by chromosome and isoenzyme analyses. PMID- 1522050 TI - Corticosteroid therapy in asthma: are metabolic considerations important? PMID- 1522052 TI - Bronchiolitis in the history of the asthmatic child. AB - In a retrospective analysis of the history of 1,700 asthmatic children, 167 (9.8%) were found to have had bronchiolitis during the first 2 years of life. These 167 cases with asthma and bronchiolitis were matched against 215 selected cases of asthma without bronchiolitis. Both groups attended our Ambulatory Care Unit for Asthma. Data were collected from the clinical cards of the children. Asthmatics who had bronchiolitis were found to have an earlier onset of asthma (p less than 0.001), earlier resolution of symptoms (p less than 0.05 total; p less than 0.01 females), and less evidence of atopy (p less than 0.005). It is suggested therefore that the bronchial hyperreactivity in asthma following bronchiolitis may have different underlying mechanisms than in the typical atopic case, without preceding bronchiolitis. Long-term follow-up studies in infants with bronchiolitis are still necessary in order to clarify the process by which bronchiolitis predisposes to bronchial hyperreactivity and asthma. The consequences of the viral infection itself may lead to pathophysiological processes that promote bronchial hyperreactivity. On the contrary, an underlying condition of bronchial hyperreactivity could be the "primum movens" of the bronchiolitis itself. PMID- 1522051 TI - Regulation of lung inflammation by local glucocorticoid metabolism: an hypothesis. PMID- 1522053 TI - Perception of bronchoconstriction in chronic asthma. AB - Twenty-nine asthmatic children were studied to assess their ability to detect the severity of their bronchoconstriction. First (STEP 0): each child was asked if he "felt asthma," inviting him to give a self-estimated obstruction score (SEOS) from 0 (no asthma) to 3 (severe asthma) and a baseline FEV1 was recorded. Then (STEP 1): methacholine was administered to all except 9 children with an FEV1 less than 80% of predicted who received saline nebulization and a second SEOS was recorded. Finally: salbutamol aerosol was administered and a third SEOS and FEV1 were obtained (STEP 2). Spearman's correlation coefficients r between SEOS and FEV1 were for the overall population -0.602, -0.517, and -0.104 at STEP 0, STEP 1, and STEP 2, respectively. The r values reduction during the trial can be due either to a decrease of children's concentration during the study or to a real difficulty in recognizing repeated changes in airway status. Some children tend to underestimate their bronchospasm. For these patients an accurate assessment of the severity of the bronchoconstriction requires an objective measurement during acute changes in asthmatic children. PMID- 1522054 TI - Development of lung function in relation to increased degree of bronchial responsiveness. AB - To study the relationship between development of lung function and bronchial responsiveness, we examined 106 subjects recruited from a random sample of 527 subjects, aged 8-18 years, from Copenhagen. Lung function and bronchial responsiveness to inhaled histamine were measured at two occasions, in 1986 and 1988. The participating subjects (n = 106) were divided into three groups: (a) 20 asthmatics with bronchial hyperresponsiveness (BHR), (b) 42 nonasthmatic subjects with BHR in 1986, and (c) 44 controls without BHR. In 1986, FEV1 expressed as percentage of predicted value, was found to be similar in the three groups (91%, 94%, and 99%, respectively). The increase in height during the observation period was found to be 5, 6, and 6 cm, respectively, in the three groups. However, at the second examination, in 1988, FEV1 was found to be significantly reduced in both asthmatics (87%) and nonasthmatic subjects (85%) compared with the controls (103%). In 1988, 16 asthmatics (80%) and 24 (57%) nonasthmatic subjects were found to have BHR, whereas none of the controls were found to have BHR. A multiple regression analysis was used to determine the correlation between change in FEV1 and potential factors of importance. The change in FEV1 was highly correlated with the presence of BHR in 1986, however, no correlation was found between change in FEV1 and change in bronchial responsiveness. In conclusion, nonasthmatic subjects with former BHR showed signs of airflow obstruction and less increase in lung function during growth irrespective of the change in level of bronchial responsiveness, which may suggest a risk for subsequent development of obstructive lung disease. PMID- 1522055 TI - An increased level of specific IgG4 antibodies against Candida albicans in patients with bronchial asthma. AB - Specific IgG4 antibodies against Candida albicans in sera were measured in 76 asthmatics. The increased level of specific IgG4 was found in cases 10-40 years old sensitive to house dust mite and/or Candida albicans, in cases with steroid dependent intractable asthma (SDIA) and in elderly cases. The frequency of SDIA was the highest in cases 41 to 60 years old with higher frequency of increased IgG4 antibodies. The results show that specific IgG4 increases in relation to IgE mediated immune response, long-term steroid therapy, and aging. All of these conditions may induce depressed cell-mediated immunity. PMID- 1522056 TI - Pulsus paradoxus in acute asthma in children. AB - One hundred children suffering from acute asthma were studied. Both pulsus paradoxus (PP) and CO2 pressure (PCO2) of the arterialized blood sample were measured in each child. The correlation between the PP and the PCO2 was not statistically significant when the latter was less than 35 mmHg (p less than 0.05). When the PCO2 was equal or higher than 35 mmHg, a directly proportional as well as statistically significant relationship with PP was found (p less than 0.00001). PP is proposed as an indirect indicator of the PCO2 on patients suffering from acute asthma, when the necessary equipment to measure the PCO2 is not available. PMID- 1522057 TI - Bdellovibrio host dependence: the search for signal molecules and genes that regulate the intraperiplasmic growth cycle. PMID- 1522058 TI - Cell surface modifications induced by calcium ion in the myxobacterium Stigmatella aurantiaca. AB - Calcium ion induces in the myxobacterium Stigmatella aurantiaca the ability to glide on solid surfaces and to become cohesive (D. F. Gilmore and D. White, J. Bacteriol. 161:113-117, 1985; B. J. Womack, D. F. Gilmore, and D. White, J. Bacteriol. 171:6093-6096, 1989). The addition of calcium ion to the growth medium resulted in the formation of extracellular fibrils, the appearance in the membrane fractions of a 30-kDa protein, and the accumulation in a low-speed centrifugal pellet of 10 polypeptides that cross-reacted with affinity-purified antibody to one of the polypeptides. One of the polypeptides, a 55-kDa protein, was present in the membrane fraction of control cells not incubated with calcium ion and was apparently translocated to the extracellular matrix during incubation in medium containing calcium ion. The 55-kDa protein was immunologically related to a 65-kDa protein located on the fibrils of another myxobacterium, Myxococcus xanthus. PMID- 1522059 TI - Anaerobic growth of Rhodopseudomonas palustris on 4-hydroxybenzoate is dependent on AadR, a member of the cyclic AMP receptor protein family of transcriptional regulators. AB - The purple nonsulfur phototrophic bacterium Rhodopseudomonas palustris converts structurally diverse aromatic carboxylic acids, including lignin monomers, to benzoate and 4-hydroxybenzoate under anaerobic conditions. These compounds are then further degraded via aromatic ring-fission pathways. A gene termed aadR, for anaerobic aromatic degradation regulator, was identified by complementation of mutants unable to grow anaerobically on 4-hydroxybenzoate. The deduced amino acid sequence of the aadR product is similar to a family of transcriptional regulators which includes Escherichia coli Fnr and Crp, Pseudomonas aeruginosa Anr, and rhizobial FixK and FixK-like proteins. A mutant with a deletion in aadR failed to grow on 4-hydroxybenzoate under anaerobic conditions and grew very slowly on benzoate. It also did not express aromatic acid-coenzyme A ligase II, an enzyme that catalyzes the first step of 4-hydroxybenzoate degradation, and it was defective in 4-hydroxybenzoate-induced expression of benzoate-coenzyme A ligase. The aadR deletion mutant was unaffected in other aspects of anaerobic growth. It grew normally on nonaromatic carbon sources and also under nitrogen-fixing conditions. In addition, aerobic growth on 4-hydroxybenzoate was indistinguishable from that of the wild type. These results indicate that AadR functions as a transcriptional activator of anaerobic aromatic acid degradation. PMID- 1522060 TI - Escherichia coli has two homologous glutamate decarboxylase genes that map to distinct loci. AB - Degenerate oligonucleotides based on the published Escherichia coli glutamate decarboxylase (GAD) protein sequence were used in a polymerase chain reaction to generate a DNA probe for the E. coli GAD structural gene. Southern blots showed that there were two cross-hybridizing GAD genes, and both of these were cloned and sequenced. The two GAD structural genes, designated gadA and gadB, were found to be 98% similar at the nucleotide level. Each gene encoded a 466-residue polypeptide, named, respectively, GAD alpha and GAD beta, and these differed by only five amino acids. Both GAD alpha and GAD beta contain amino acid residues which are highly conserved among pyridoxal-dependent decarboxylases, but otherwise the protein sequences were not homologous to any other known proteins. By restriction mapping and hybridization to the Kohara miniset library, the two GAD genes were located on the E. coli chromosome. gadA maps at 4046 kb and gadB at 1588 kb. Neither of these positions is in agreement with the current map position for gadS as determined by genetic means. Analysis of Southern blots indicated that two GAD genes were present in all E. coli strains examined, including representatives from the ECOR collection. However, no significant cross hybridizing gene was found in Salmonella species. Information about the DNA sequences and map positions of gadA and gadB should facilitate a genetic approach to elucidate the role of GAD in E. coli metabolism. PMID- 1522061 TI - Localization of a Porphyromonas gingivalis 26-kilodalton heat-modifiable, hemin regulated surface protein which translocates across the outer membrane. AB - We recently identified a 26-kDa hemin-repressible outer membrane protein (Omp26) expressed by the periodontal pathogen Porphyromonas gingivalis. We report the localization of Omp26, which may function as a component of a hemin transport system in P. gingivalis. Under hemin-deprived conditions, P. gingivalis expressed Omp26, which was then lost from the surface after a shift back into hemin-rich conditions. Experiments with 125I labeling of surface proteins to examine the kinetics of mobilization of Omp26 determined that it was rapidly (within less than 1 min) lost from the cell surface after transfer into a hemin-excess environment. When cells grown under conditions of hemin excess were treated with the iron chelator 2,2'-bipyridyl, Omp26 was detected on the cell surface after 60 min. One- and two-dimensional sodium dodecyl sulfate-polyacrylamide gel electrophoresis and immunoblot analyses using purified anti-Omp26 monospecific polyclonal immunoglobulin G antisera established that Omp26 was heat modifiable (39 kDa unheated) and consisted of a single protein species. Immunogold labeling of negatively stained and chemically fixed thin-section specimens indicated that Omp26 was associated with the cell surface and outer leaflet of the P. gingivalis outer membrane in hemin-deprived conditions but was buried in the deeper recesses of the outer membrane in hemin-excess conditions. Analysis of subcellular fractions of P. gingivalis grown either in hemin-excess or hemin-deprived conditions detected Omp26 only in the cell envelope fraction, not in the cytoplasmic fraction or culture supernatant. Limited proteolytic digestion of hemin-deprived P. gingivalis with trypsin and proteinase K verified the surface location of Omp26 as well as its susceptibility to proteolytic digestion. Heat shock treatment of hemin-excess-grown P. gingivalis also resulted in Omp26 translocation onto the outer membrane surface even in the presence of hemin. Furthermore, hemin repletion of heat-shocked, hemin-deprived P. gingivalis did not result in Omp26 translocation off the outer membrane surface, suggesting that thermal stress inactivates this transmembrane event. This newly described outer membrane protein appears to be associated primarily with the outer membrane, in which it is exported to the outer membrane surface for hemin binding and may be imported across the outer membrane for intracellular hemin transport. PMID- 1522062 TI - Purification and characterization of a thermostable beta-xylosidase from Thermoanaerobacter ethanolicus. AB - A highly thermostable beta-xylosidase, exhibiting similarly high activities for arylxylose and arylarabinose, was purified (72-fold) to gel electrophoretic homogeneity from the ethanologenic thermophilic anaerobe Thermoanaerobacter ethanolicus. The isoelectric point is pH 4.6; the apparent molecular weight is around 165,000 for the native enzyme (gel filtration and gradient polyacrylamide gel electrophoresis) and 85,000 for the two subunits (sodium dodecyl sulfate polyacrylamide gel electrophoresis). The enzyme exhibited the highest affinity towards p-NO2-phenyl xyloside (pNPX) (substrate concentration for half-maximal activity = 0.018 mM at 82 degrees C and pH 5.0) but the highest specific activity with p-NO2-phenylarabinofuranoside. T(opt), 5 min, the temperature for the maximum initial activity in a 5-min assay of the purified enzyme, was observed around pH 5.9 and 93 degrees C; however at 65 and 82 degrees C, the pH optimum was 5.0 to 5.2, and at this pH the maximal initial activity was observed at 82 degrees C (pH 5.0 to 5.5). The pH curves and temperature curves for arylxylosides as substrates differed significantly from those for arylarabinosides as substrates. An incubation for 3 h at 82 degrees C in the absence of substrate reduced the activity to around 75%. At 86 degrees C the half-life was around 15 min. With pNPX as the substrate, an Arrhenius energy of 69 kJ/mol was determined. The N-terminal sequence did not reveal a high similarity to those from other published enzyme sequences. PMID- 1522063 TI - Molecular characterization of the sor gene, which encodes the sulfur oxygenase/reductase of the thermoacidophilic Archaeum Desulfurolobus ambivalens. AB - A 5.8-kbp HindIII fragment containing the sor gene which encodes the aerobically induced sulfur oxygenase/reductase of the thermoacidophilic, chemolithoautotrophic, and facultatively anaerobic archaeum Desulfurolobus ambivalens, was cloned in pUC18 by using an oligonucleotide derived from the N terminal amino acid sequence for identification (pSOR-1/17). The native enzyme is a 550,000-molecular-weight oligomer composed of single 40,000-molecular-weight subunits; this oligomer is capable of the simultaneous oxidation and reduction of sulfur (A. Kletzin, J. Bacteriol. 171:1638-1643, 1989). From the fragment, 3,025 bp that contained the entire sor gene were sequenced. The sor gene encoded a protein with 309 amino acid residues (molecular weight, 35,317). The transcript length was determined by Northern RNA hybridization to be 960 to 1,020 nucleotides, and the transcriptional start site was mapped by primer extension analysis. The transcript of the sor gene in aerobically grown cells was amplified 38- to 42-fold relative to that in anaerobically grown cells. An initial transcriptional characterization of three neighboring genes of unknown function is also reported. PMID- 1522064 TI - Regulation of the macrolide-lincosamide-streptogramin B resistance gene ermD. AB - The erythromycin resistance gene ermD, which encodes an rRNA methylase protein, has an unusually long leader region (354 nucleotides). Previously, a single promoter-proximal leader peptide coding sequence was recognized from the nucleotide sequence, and erythromycin-induced ribosome stalling in this sequence was proposed to be required for the induction of methylase translation. We characterized spontaneously occurring and in vitro-constructed leader region mutations in an effort to understand the function of various segments of the long ermD leader region. A second leader peptide coding sequence was identified, and the location of insertion and point mutations that expressed ermD methylase constitutively suggested that translation of the second leader peptide is controlled by ribosome stalling in the first leader peptide. From Northern RNA blot analysis of ermD transcription, it appears that regulation of ermD expression is not by transcriptional attenuation. PMID- 1522065 TI - Oligopeptidase A is required for normal phage P22 development. AB - The opdA gene of Salmonella typhimurium encodes an endoprotease, oligopeptidase A (OpdA). Strains carrying opdA mutations were deficient as hosts for phage P22. P22 and the closely related phages L and A3 formed tiny plaques on an opdA host. Salmonella phages 9NA, KB1, and ES18.h1 were not affected by opdA mutations. Although opdA strains displayed normal doubling times and were infected by P22 as efficiently as opdA+ strains, the burst size of infectious particles from an opdA host was less than 1/10 of that from an opdA+ host. This decrease resulted from a reduced efficiency of plating of particles from an opdA infection. In the absence of a functional opdA gene, most of the P22 particles are defective. To identify the target of OpdA action, P22 mutants which formed plaques larger than wild-type plaques on an opdA mutant lawn were isolated. Marker rescue experiments using cloned fragments of P22 DNA localized these mutations to a 1-kb fragment. The nucleotide sequence of this fragment and a contiguous region (including all of both P22 gene 7 and gene 14) was determined. The mutations leading to opdA independence affected the region of gene 7 coding for the amino terminus of gp7, a protein required for DNA injection by the phage. Comparison of the nucleotide sequence with the N-terminal amino acid sequence of gp7 suggested that a 20-amino acid peptide is removed from gp7 during phage development. Further experiments showed that this processing was opdA dependent and rapid (half-life, less than 2 min) and occurred in the absence of other phage proteins. The opdA-independent mutations lead to mutant forms of gp7 which function without processing. PMID- 1522067 TI - Expression of Vi antigen in Escherichia coli K-12: characterization of ViaB from Citrobacter freundii and identity of ViaA with RcsB. AB - The Vi antigen in Salmonella typhi is stably expressed and may act to protect the strain against the defensive system of the host. Citrobacter freundii, not usually a common human pathogen, also expresses the Vi antigen but expresses it unstably, exhibiting a reversible transition between the Vi+ and Vi- states. Two widely separated chromosomal regions, ViaA and ViaB, are needed for Vi synthesis. Escherichia coli K-12 harboring a functional ViaB plasmid can also express Vi antigen, but the cloned ViaB sequence can only be stably maintained and expressed in recA hosts. Vi- derivatives arise either through IS1-like insertional events occurring in ViaB sequences or by chromosomal mutations at the ViaA region. P1vir mapping indicates that the ViaA mutations are located at min 47.75 on the E. coli chromosome. All the spontaneous viaA mutants isolated from E. coli and S. typhi were identified as rcsB mutants by complementation tests using plasmid pJB100. Introduction of rcsA::Tn10 into E. coli harboring functional ViaB sequences eliminates the expression of Vi antigen. These results indicate that Vi antigen synthesis is regulated by the same regulatory proteins involved in colanic acid synthesis in E. coli. PMID- 1522066 TI - Origin, structure, and regulation of argK, encoding the phaseolotoxin-resistant ornithine carbamoyltransferase in Pseudomonas syringae pv. phaseolicola, and functional expression of argK in transgenic tobacco. AB - Pseudomonas syringae pv. phaseolicola produces the tripeptide N delta(N'-sulfo diaminophosphinyl)-ornithylalanyl-homoarginin e (phaseolotoxin), which functions as a chlorosis-inducing toxin in the bean halo blight disease by inhibiting ornithine carbamoyltransferase (OCT). The bacterium possesses duplicate OCT genes, one of which, argK, encodes a toxin-resistant enzyme (ROCT) and imparts resistance to phaseolotoxin. We sequenced the argK gene from strain NPS3121, defined its promoter region, analyzed its regulation, and characterized its transcripts. The gene probably originated from another organism, since it is very distantly related to the argF gene encoding the housekeeping toxin-sensitive OCT and has low G+C content compared with the bacterial genome as a whole and with other protein-coding genes from P. syringae pv. phaseolicola. Optimized alignments of 13 OCT sequences allowed us to define key residues that may be responsible for toxin resistance and to identify a distinct prokaryotic amino acid signature, in ROCT, which argues for a prokaryotic origin of argK. An in frame fusion of the argK coding region with the chloroplast transit peptide segment of the pea rbcS gene was introduced in Nicotiana tabacum by Agrobacterium mediated transformation. The presence of an ROCT activity in transgenic plants was demonstrated by in vitro and in vivo assays. Some plants were toxin resistant, suggesting that pathogen-derived resistance to the toxin should be feasible in the pathogen's host. PMID- 1522068 TI - Characterization of the Campylobacter fetus sapA promoter: evidence that the sapA promoter is deleted in spontaneous mutant strains. AB - Wild-type Campylobacter fetus cells possess S-layer proteins (S+ phenotype), whereas after laboratory passage, spontaneous stable mutants that do not express these proteins (S- phenotype) arise. To determine the molecular mechanisms by which C. fetus changes to the S- phenotype, we studied wild-type strain 23D, from which the sapA gene encoding the 97-kDa S-layer protein has been cloned, and strain 23B, a spontaneous S- mutant. We compared these strains with another pair of strains, LP (S+) and HP (S-). Southern analysis with the cloned sapA gene as a probe indicated that both pairs of strains have multiple sapA homologs. Using gene disruption and replacement techniques, we constructed an isogenic strain of 23D that differed only in sapA expression (strain 23D:401:1). A 6.0-kb HindIII fragment from 23D:401:1 containing 3.4 kb of sapA upstream region then was cloned into pBluescript to produce pBG101. Nucleotide sequence analysis of sapA upstream region revealed a consensus promoter at -121 bp from the translational start site. Primer extension analysis placed a single in vivo transcription initiation site at the -114-bp position of sapA. A DNA probe derived from the sapA promoter region hybridized to a 5.5-kb HindIII fragment of chromosomal DNA from strain 23D but not to DNA from strain 23B. Northern RNA blot analysis showed no sapA mRNA in strain 23B. These data indicate that the lack of S-layer protein expression in spontaneous mutant strains is caused by the deletion of promoter sequences. PMID- 1522069 TI - Determination of the mechanism of retrotransfer by mechanistic mathematical modeling. AB - Two mathematical models to elucidate the mechanism of retromobilization (or retrotransfer), that is, the ability of conjugative plasmids to mobilize genes into the cell containing the conjugative plasmid, were developed. This study deals with retromobilization of nonconjugative plasmids (Tra-Mob+). Plasmid transfer was modeled by two mass action models. The first is based on the hypothesis that retromobilization of the Tra-Mob+ vector occurs in one step, by means of the pilus formed by the Tra+ plasmid in the original host. In the second model, retromobilization is considered to be a two-step process involving two transfer events. The first step involves the transfer of the Tra+ plasmid from the recipient cell to the donor of the nonconjugative vector, and during the second encounter the nonconjugative vector is mobilized toward the recipient. Since the relationships between the number of transconjugants and the number of recipients for the two models are different, filter matings were performed for short time periods with different initial densities of the recipient population. Comparison of the numbers of transconjugants with the results of the mathematical equations confirmed the hypothesis that retromobilization is a one-step conjugation process. PMID- 1522070 TI - Cloning, sequencing, and enhanced expression of the dihydropteroate synthase gene of Escherichia coli MC4100. AB - The Escherichia coli gene coding for dihydropteroate synthase (DHPS) has been cloned and sequenced. The protein has 282 amino acids and a compositional molecular mass of 30,314 daltons. Increased expression of the enzyme was realized by using a T7 expression system. The enzyme was purified and crystallized. A temperature-sensitive mutant was isolated and found to express a DHPS with a lower specific activity and lower affinities for para-aminobenzoic acid and sulfathiazole. The allele had a point mutation that changed a phenylalanine codon to a leucine codon, and the mutation was in a codon that is conserved among published DHPS sequences. PMID- 1522071 TI - Role of pilA, an essential regulatory gene of Neisseria gonorrhoeae, in the stress response. AB - Sequence analysis has shown that PilA, a transcriptional regulator of pilin gene expression in Neisseria gonorrhoeae, has extensive homology with the 54-kDa protein of the signal recognition particle of eukaryotes and its receptor, as well as with two proteins of Escherichia coli, FtsY and Ffh, which have been proposed to be a part of a signal recognition particle-like apparatus. We tested the putative role of PilA in protein export in N. gonorrhoeae and did not find any effect. However, we did observe induction of a heat shock response and a previously described slow-growth phenotype when PilA function was impaired. We also examined the interference of pilA expression in E. coli with the function of the products of ftsY and ffh and observed an accumulation of pre-beta-lactamase. We argue against a direct role for PilA in protein export in gonococci and propose instead that PilA is involved in the modulation of cell growth rate in response to different environmental conditions. PMID- 1522072 TI - The cytoplasmic peptidoglycan precursor of vancomycin-resistant Enterococcus faecalis terminates in lactate. AB - Vancomycin resistance plasmids in enterococci carry the genes vanH and vanA, which encode enzymes catalyzing, respectively, the reduction of 2-keto acids to 2 D-hydroxy acids and the addition of D-hydroxy acids to D-alanine. It has therefore been postulated that resistant cells produce peptidoglycan precursors that terminate in the depsipeptide D-alanine-2-D-hydroxy acid rather than the dipeptide D-alanine-D-alanine, thus preventing vancomycin binding (M. Arthur, C. Molinas, T. D. H. Bugg, G. D. Wright, C. T. Walsh, and P. Courvalin, Antimicrob. Agents Chemother. 36:867-869, 1992). In the present work, a cytoplasmic peptidoglycan precursor was isolated from vancomycin-resistant Enterococcus faecalis and analyzed by mass spectrometry, which suggested the structure UDP-N acetyl-muramyl-L-Ala-D-Glu-L-Lys-D-Ala-D-lactate. PMID- 1522073 TI - An ordered clone bank for chromosome I of Saccharomyces cerevisiae. AB - Chromosome I of Saccharomyces cerevisiae DC5 rho 0 was dissected into segments with an average size of 14.0 kb and cloned into lambda phage vectors. The physical maps of the resultant clones, totaling 205.9 kb, were used to construct an ordered clone bank of this chromosome. PMID- 1522074 TI - Directed mutagenesis in an asporogenous methylotrophic yeast: cloning, sequencing, and one-step gene disruption of the 3-isopropylmalate dehydrogenase gene (LEU2) of Candida boidinii to derive doubly auxotrophic marker strains. AB - A model system for one-step gene disruption for an asporogenous methylotrophic yeast, Candida boidinii, is described. In this system, the 3-isopropylmalate dehydrogenase gene (C. boidinii LEU2) was selected as the target gene for disruption to derive new host strains for transformation. First, the C. boidinii LEU2 gene was cloned, and its complete nucleotide sequence was determined. Next, the LEU2 disruption vectors, which had the C. boidinii URA3 gene as the selectable marker, were constructed. Of the Ura+ transformants obtained with these plasmids, more than half showed a Leu- phenotype. Finally, the double marker strains of C. boidinii were derived. When vectors with repeated flanking sequences of the C. boidinii URA3 gene were used for gene disruption, Leu- Ura+ transformants changed spontaneously to a Leu- Ura- phenotype ca. 100 times more frequently than they did when plasmids without the repeated sequences were used. Southern analysis showed that these events included a one-step gene disruption and a subsequent popping out of the C. boidinii URA3 sequence from the transformant chromosome. PMID- 1522075 TI - Characterization of a light-regulated gene encoding a new phycoerythrin associated linker protein from the cyanobacterium Fremyella diplosiphon. AB - Cyanobacteria utilize multimeric protein complexes, the phycobilisomes, as their major light-harvesting antennae. Associated with the chromophorylated phycobiliproteins in these complexes are nonpigmented proteins, designated linker proteins. These linker proteins are believed to mediate assembly of the phycobilisome and energy transfer to the photosynthetic reaction center. We cloned and sequenced a gene, cpeE, encoding a previously uncharacterized linker protein which is expressed in green light in Fremyella diplosiphon. This gene is part of an operon containing two other phycoerythrin-associated linker genes, cpeC and cpeD. Transcription of the cpeCDE operon in green light results in two predominant species of mRNA of approximately 2,100 and 3,200 nucleotides. The shorter transcript encodes only CpeC and CpeD, while the longer contains the coding regions for all three linker proteins. By altering the pH of the resolving gel and the running buffer during sodium dodecyl sulfate-polyacrylamide gel electrophoresis, this third linker protein CpeE can be resolved from the rod-core linker and the other rod linker proteins. The three proteins have an overall similarity of approximately 62%, and the genes encoding the three proteins are approximately 59% identical. PMID- 1522076 TI - The medical consequences of the selection of an antidepressant. AB - Patients who take antidepressants risk developing adverse drug reactions with medical sequelae. I will review noncardiac adverse drug reactions to antidepressant organized around (1) the effect of antidepressants on neurotransmitter systems and monoamine oxidase along with effects on concomitant physiologic systems, (2) side effects that are seen clinically but may or may not be related to antidepressant effects on neurotransmitter systems, (3) medical conditions that affect the choice of certain antidepressants, (4) antidepressant toxicity with overdose, and (5) recommendations for using antidepressants with the least probability of causing severe adverse drug reactions. PMID- 1522077 TI - Treating the depressed patient with cardiovascular problems. AB - A multidimensional relationship exists between cardiovascular disease and affective disorder that includes the observations that (1) there is a high rate of depression in the postmyocardial infarction period, (2) the presence of depressive illness adversely affects the prognosis of cardiac disease, and (3) depressed patients have a higher-than-expected rate of sudden cardiovascular death. The authors discuss these topics and the clinical management of depression in patients with significant preexisting heart disease. The cardiovascular effects of the tricyclic antidepressants and recently introduced nontricyclic antidepressants are reviewed with a focus on how the clinician can safely and effectively treat affective disorder in patients with severe cardiac disease. PMID- 1522078 TI - Long-term treatments of recurrent depressive disorders. AB - Many, if not most, depressive disorders become recurrent conditions. It is now clear that virtually all recently remitted patients should receive 4 to 6 months of continuation therapy. Moreover, this phase of treatment should continue until the patient has achieved a clear-cut, durable period of recovery. Further, an extended course of maintenance pharmacotherapy is recommended for those patients at risk for subsequent recurrent episodes. In this paper, the rationale for long term treatment is presented and common strategies are reviewed. Depressive disorders appear to become more autonomous, severe, and potentially refractory with each new episode. Thus, prevention of recurrent depression remains the best available strategy to ensure an optimal long-term outcome for patients with recurrent affective disorders. PMID- 1522079 TI - Treatment of depression in special populations. AB - The purpose of this review is to set forth guidelines for the treatment of depression in several special populations: (1) the elderly (both ambulatory and institutionalized); (2) patients with concurrent neurologic disorders (Alzheimer's disease, Parkinson's disease, and stroke) and depression; and (3) patients with bereavement-related depression. This is a selective review of studies published in the past 10 years that have utilized structured psychiatric interviewing, randomized clinical trials, and/or monitoring of plasma antidepressant levels. Published data support specific efficacy and safety claims for both pharmacotherapeutic and psychotherapeutic approaches to the treatment of major depression in elderly ambulatory and institutionalized patients. In the case of depression associated with Alzheimer's, Parkinson's, and stroke, there is also evidence of efficacy for antidepressant medication. Finally, bereavement related syndromal depression appears to respond to antidepressant medication, but further controlled evaluation is desirable. As emphasized by the 1991 National Institutes of Health Consensus Development Conference on the Diagnosis and Treatment of Depression in Late Life, depression in the elderly should be recognized as treatable and should be treated vigorously. Rather than being dismissed as a normal reaction to the multiple medical and psychosocial burdens of late life, it should be treated appropriately to reduce an important source of excess disability. PMID- 1522080 TI - Somatic therapy for major depressive disorder: selection of an antidepressant. AB - Major depressive disorder is a major health concern. It adversely affects the patient, the family, and society. While the consequences can be devastating and life-threatening, this condition has an excellent prognosis when properly identified and treated. Somatic therapy plays a pivotal role in inducing and maintaining a remission and preventing recurrent attacks. There are now five major classes of antidepressants which differ in terms of their clinical spectra of antidepressant activity, their safety and tolerability, their likelihood of pharmacodynamic and pharmacokinetic interactions with concomitantly prescribed drugs, ease of administration, and physician confidence, which is in large measure a reflection of the extent and quality of their human exposure database. The proper selection and management of antidepressant pharmacotherapy is based on an understanding of these differences. PMID- 1522081 TI - Effect of non-surgical periodontal therapy in an undergraduate dental clinic. Results one year following treatment. AB - The aim of the present study was to evaluate the effectiveness of non-surgical treatment of moderately to severely advanced periodontitis in patients at the Department of Periodontology of the Aristotle University of Thessaloniki. The patients were treated by senior students of the Dental School under the supervision of specialized personnel. The conservative treatment consisted of oral hygiene instructions and repeated instrumentation (scaling and root planing) for a period of about 3 months. Seventeen patients with advanced periodontitis participated in the study. The following data were recorded: 1. Gingival index (Silness and Loe, 1963), 2. Plaque index (Loe and Silness 1964), 3. Bleeding on probing and 4. Pocket depth and probing attachment level. The measurements were taken by the same examiner four times, that is at baseline, immediately after completion of the conservative therapy, 6 months and 12 months after treatment. Measurements from single and multi-rooted teeth were divided into three groups with respect to the initial pocket depth (less than or equal to 3 mm, 4-6 mm, greater than or equal to 7 mm). The findings of the present study demonstrated that non-surgical therapy can achieved a marked reduction in bleeding on probing scores and pocket depth 12 months after treatment. A gain in probing attachment levels was found for sites with initially deep (greater than or equal to 7 mm) and moderate (4-6 mm) pockets, while in sites with initially shallow pockets (less than or equal to 3.0 mm), a loss of attachment level was established. PMID- 1522082 TI - Growth of the skeletal units of the rat mandible in acute renal failure experimental model. AB - A study of the effect of acute renal failure (ARF) on the growth of the skeletal units of the mandible was performed. Male Wistar rats weighing 35-40 g were assigned to three groups. One of the groups received a basal choline-deficient diet ad libitum. A second group was pair-fed with the first one and was given a basal diet supplemented with 0.35 g choline chloride/100 g of diet. The third group was fed a basal diet plus 0.35 g choline chloride/100 g of diet ad libitum and used as the normal control. Body length, renal function parameters and measurements of the mandible were recorded at the end of a 12-day period on the different diets. Food intake and body weight were recorded every day. Plasma urea and creatinine concentrations markedly increased over the first 12 days of exposure to a choline-deficient diet. Significant increases in urine volume and significant depressions in urine osmolality were also observed. The average body weight and body length gains for rats given the choline-deficient diet were lower than those of control rats. There were no significant differences between the average body weight and body length of pair-fed and normal rats. All skeletal measurements of the mandible of the choline-deficient group differed significantly from those of the control group. These differences varied between 7% and 30%. The skeletal units of the mandible of the pair-fed group did not differ significantly from ad libitum controls. This study suggests that this rat model can be used for the investigation of the different alterations observed in uremia.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1522083 TI - [Gingival hyperplasia secondary to the use of calcium antagonists: analysis]. AB - Calcium antagonists are drugs restricting transmembrane calcium delivery. They possess a wide range of action against vasoconstriction and spastic reactions and were therefore initially recommended for the treatment of angina pectoris. With the increasing number and classes of calcium antagonists new therapeutic indications have emerged. Cases of gingival hyperplasia associated with their use are repeatedly reported, therefore the question deserves to be restated. The aim of the present study was to discuss the clinical, pathologic and pathogenetic features bases on an investigation carried out in a Department of Cardiology, on a case observation and on review of published cases in the international literature. PMID- 1522084 TI - [Antifungal varnish in the treatment of denture stomatitis]. AB - The efficacy of a single-dose application of miconazole varnish in the treatment of denture stomatitis was compared with miconazole gel applied three times/day for 15 days. Among 288 wearers of complete dentures 50 patients severely affected by denture stomatitis and heavily colonized by Candida, were selected. The patients were assigned randomly to two groups: a miconazole varnish group and a gel group. All patients were examined 7 times: before starting the treatment (day 0); during treatment (day 3, 7 and 14); after treatment (day 21, 28 and 35). At each examination a photograph of the palatal mucosa was obtained and quantitative cultures of Candida from the lesions and the fitting denture surface were performed. At day 14 the inflammation was reduced to the same degree in the two groups of patients. A comparison of the antifungal effect, i.e. reduction of the yeast score, showed no significant difference between the two groups. Maximum reduction of the number of yeasts was obtained at day 14. From that moment, recolonization started; thus, about 60% of the treated patients whether it was with the gel or the varnish was positive of Candida by day 35. In conclusion, the present study showed no difference in the clinical and antifungal effect of a single-dose application of miconazole varnish compared with miconazole gel. The varnish seemed to be better with respect to the posology as the total dose of miconazole is minimal and only one application is necessary. Treatment with the miconazole varnish seems particularly indicated in debilitated and non cooperative patients suffering from Candida-associated denture stomatitis. PMID- 1522085 TI - Penetration of glutaric dialdehyde into human dentine as measured by changes in dentine microhardness and dentine dimensions. AB - Microhardness indentation lengths were measured on human dentine sections unfixed and fixed with glutaric dialdehyde (GDA) at pH 7. Fixed dentine was found to be softer than unfixed dentine. Indentation length increased by approximately 10% after fixation in a buffered 5% GDA solution at pH 7. Using this effect the variation of indentation length in the direction of the penetrating GDA as a function of fixation time was measured. Describing the penetration in the mineralized matrix as diffusion in a plane sheet, a diffusion coefficient of 0.5.10(-12); m2/s was calculated. Dimensional changes of the dentine due to fixation were also measured. Dentine was found to expand in both the direction parallel (approximately 0.4%) and perpendicular (approximately 2%) to the tubules. PMID- 1522086 TI - Differences between primary and permanent teeth in posteruptive age dependency of radiological changes in enamel during the development of approximal caries. AB - A longitudinal radiological study of children (N = 549) who participated in a comprehensive preventive maintenance program showed that caries related events in the approximal surfaces of permanent teeth differed from those in deciduous teeth. Changes in the approximal surfaces of the younger permanent teeth were more pronounced than of the older primary teeth and differed significantly from 1 year to 2.5 years. These findings can be explained by posteruptive maturation of tooth enamel. PMID- 1522087 TI - The effect of an experimental mouthrinse on enamel lesion remineralization in vitro. AB - This paper describes the effect of a 2 ppm fluoride containing, slightly acidic mouthrinse (pH = 6) on the remineralization of enamel lesions in vitro. The rinse was applied twice daily for 2 min, on about 85 microns in depth artificial lesions. Artificial enamel lesions were formed at pH = 5 in a 6% CMC gel. The lesions were subsequently remineralized in vitro in a neutral remineralizing solution (1.5 mM Ca and 0.9 mM phosphate) with or without the application of the rinse. After 3 weeks the samples were evaluated by means of quantitative microradiography. The results showed that a statistically significant reduction in lesion depth occurred of 48 and 29% with or without rinse application, with respect to the original lesion depth. The effect of the rinse compared with no rinse decreased the lesion depth by 40%. The data indicate that application of a slightly acidic rinse with 2 ppm fluoride applied twice a day, stimulates the remineralization at the lesion front and does not lead to blocking of enamel pores observed after acidic, high level F applications (APF). PMID- 1522088 TI - A quantitative evaluation of periprosthetic bone-remodeling after cementless total hip arthroplasty. AB - Dual-energy x-ray absorptiometry analysis was used to determine the periprosthetic bone-mineral content of ten femora that had been obtained at the autopsies of five elderly patients who had had an AML (anatomic medullary locking) prosthesis in situ for seventeen to eighty-four months. Clinical radiographs showed resorptive remodeling changes characteristic of femora containing this implant. Before the absorptiometry was performed, an identical prosthesis had been inserted into the contralateral, normal femur of each cadaver. The mean difference in the periprosthetic bone-mineral content between the remodeled femora and the femora in which the prosthesis had been implanted post mortem ranged from 7 to 52 per cent, with the bone-mineral content always less in the remodeled femora. The greatest mean decrease in bone-mineral content (45 per cent) occurred adjacent to the proximal one-third of the remodeled femora. The percentage decrease in periprosthetic bone-mineral content in the remodeled femora had an inverse linear relationship with the corresponding bone mineral content of the contralateral control femora. Preoperative analysis of bone density may therefore be useful for prediction of the extent of resorptive bone-remodeling after total hip replacement. PMID- 1522089 TI - The use of computerized tomography in the measurement of glenoid version. AB - Computerized tomography was done preoperatively on twenty shoulders (thirteen patients) in which there were severe arthritic changes, to measure glenoid version. Ten of the twenty shoulders had osteoarthrosis; eight, rheumatoid arthritis; and two, gouty arthritis. To help determine normal values, computerized tomographic scans of the chest of sixty-three patients who did not have roentgenographic evidence of disease of the shoulder were studied retrospectively for comparison as a control group. In the group of patients who had severe arthritis, the mean glenoid orientation was 11 degrees of retroversion (range, 2 degrees of anteversion to 32 degrees of retroversion). The computerized tomographic scans showed uneven wear of the glenoid surface, osteophytes, large cysts, and posterior displacement of the humeral head. In the control group, the mean orientation of the glenoid was 2 degrees of anteversion (range, 14 degrees of anteversion to 12 degrees of retroversion). The difference between the groups was significant (p less than 0.0001). Glenoid retroversion was increased in the patients who had severe arthritis, and the computerized tomographic scans accurately revealed the extent and pattern of erosion of the bone. PMID- 1522090 TI - Transfer of the tibialis anterior for calcaneus deformity in myelodysplasia. AB - We evaluated the results of transfer of the tibialis anterior in the management of calcaneus deformity in young patients who had myelodysplasia; fifteen patients (twenty-two feet) were operated on between 1978 and 1985. The neural deficit was at the fourth and fifth lumbar levels. The average age at the time of the operation was seven years and two months (range, two to nineteen years). The average age at the latest follow-up was thirteen years (range, five to twenty four years). The average duration of follow-up was five years and ten months (range, two to eleven years). Seventeen feet (twelve patients) had a good result (no ulceration of the heel or osteomyelitis and correction of the calcaneus deformity), and five feet (three patients) had a poor result (persistent ulceration, signs of osteomyelitis, recurrent or persistent calcaneus deformity, or the need for additional operative intervention). Children who were less than five years old had a better outcome, as determined by the Fisher exact test (p less than 0.5). PMID- 1522091 TI - Stability of an ankle arthrodesis fixed by cancellous-bone screws compared with that fixed by an external fixator. A biomechanical study. AB - Twenty-three fresh-frozen human specimens were subjected to ankle arthrodesis and fixation with two cancellous-bone screws. The specimens were then subjected to four newton-meters of manually applied tibial torque, plantar flexion dorsiflexion moment, and medial-lateral bending moment; relative rotation between the tibia and the talus was recorded for each mode of testing. A Calandruccio triangular compression device was then applied to threaded pins penetrating the tibia and talus, the screws were removed, and the test sequence was repeated. Tibiotalar motions recorded with both systems of fixation were markedly affected by the quality of the bone. When less than 2 degrees of total tibiotalar rotation was recorded in response to four newton-meters of manually applied internal external tibial torque, all specimens demonstrated less torsional rotation with the screw fixation than with the external fixator. The mean rotations produced by medial-lateral bending moment were equivalent for both systems of fixation. When torsional rotations with the use of screw fixation were greater than 2 degrees, all specimens demonstrated more torsional rotation with the screws than with the external fixator, and all but one specimen had more medial-lateral rotation with the screws than with the fixator. For applied plantar flexion-dorsiflexion moment, twenty-two of the twenty-three specimens demonstrated more rotation with the Calandruccio fixator than with the screws; this was due in part to motion permitted at the hinge points of the frame itself. PMID- 1522092 TI - Cotrel-Dubousset instrumentation for adolescent idiopathic scoliosis. AB - We evaluated the results of segmental fixation of the spine with Cotrel-Dubousset instrumentation in ninety-five patients who had adolescent idiopathic scoliosis. The instrumentation was used in an attempt to achieve three-dimensional correction of the scoliosis, maintain lumbar lordosis, create thoracic kyphosis, and avoid the need for a postoperative cast or brace. The patients were followed for twenty-four to sixty-four months (average, thirty-five months). Cotrel Dubousset instrumentation provided an average correction of the coronal curve of 48 per cent at the time of the most recent follow-up. The normal sagittal curves at the thoracolumbar junction and in the lumbar spine were maintained, and the thoracic kyphosis was increased slightly (average, +7 degrees). Apical translation improved an average of 60 per cent, and apical rotation improved an average of 11 per cent. Forced vital capacity improved an average of 21 per cent, and the one-second forced expiratory volume improved an average of 18 per cent. There were no major neurological deficits. A symptomatic pseudarthrosis developed in one patient. Postoperatively, decompensation of the spine developed in five of the first twenty-six patients who had a Type-II or Type-III curve. This complication was avoided in the last twenty-four patients who had a Type-II or Type-III curve by means of a stricter adherence to the definition of a Type-II curve, and reversal of the bend of the rod and the hooks between the caudal neutral and stable vertebrae. The major advantages of Cotrel-Dubousset instrumentation are the stable fixation that is achieved and the preservation of segmental lumbar lordosis. PMID- 1522093 TI - The effect of malunion on functional outcome after plate fixation of fractures of both bones of the forearm in adults. AB - Fifty-five adults who had a fracture of both bones of the forearm were managed with plating and were followed for a mean of six years (range, one year to sixteen years and two months) with functional and radiographic assessment. Malunion was quantified by measurement of the amount and location of the maximum radial bow in relation to the contralateral, normal forearm. Fifty-four of the radial and fifty-four of the ulnar fractures united. Eighty-four per cent of the patients had an excellent, good, or acceptable functional result, according to the criteria of Grace and Eversmann. Bone-grafting did not affect the rate of union. Restoration of the normal radial bow was related to the functional outcome. A good functional result (more than 80 per cent of normal rotation of the forearm) was associated with restoration of the normal amount and location of the radial bow (p less than 0.05 and p less than 0.005). Similarly, the recovery of grip strength was associated with restoration of the location of the radial bow toward normal (p less than 0.005). PMID- 1522094 TI - Osteosarcoma as a second malignant neoplasm in children. AB - Nine patients who had an osteosarcoma that had developed as a second malignant neoplasm in a previously irradiated site were managed at a major center for the treatment of tumors in children. The doses of radiation had averaged 4144 centigray (range, 2300 to 8000 centigray) and chemotherapy had been administered, when appropriate, for the primary malignant lesion (Ewing sarcoma, malignant fibrous histiocytoma, Hodgkin lymphoma, neuroblastoma, neurofibrosarcoma, rhabdomyosarcoma, and Wilms tumor). The interval between the initial treatment and the diagnosis of the secondary sarcoma averaged ten years and one month (range, five years and ten months to twenty-one years and nine months). Three patients were alive, two of them with active disease, at the time of writing. The other six had died within three years (average, fifteen months) after the second diagnosis. The prevalence of secondary osteosarcoma is increasing as the survival of children who have a malignant lesion increases. Plans for tumor therapy should take into account the risk of this complication, which is usually fatal. PMID- 1522095 TI - Intraoperative anaphylaxis secondary to allergy to latex in children who have spina bifida. Report of two cases. PMID- 1522096 TI - Intraoperative anaphylaxis due to allergy to latex. Report of two cases. PMID- 1522097 TI - Osteolytic cyst-like area associated with polyethylene and metallic debris after total knee replacement with an uncemented vitallium prosthesis. A case report. PMID- 1522098 TI - Fatal air embolism after prophylactic intramedullary nailing. A case report. PMID- 1522099 TI - Allergy to latex in patients who have myelodysplasia. Relevance for the orthopaedic surgeon. PMID- 1522100 TI - Ingrowth of bone in failed fixation of porous-coated femoral components. PMID- 1522101 TI - Pericardial tamponade secondary to perforation by central venous catheters in orthopaedic patients. PMID- 1522102 TI - A new diagnostic test for carpal tunnel syndrome. PMID- 1522103 TI - The effect of a ligament-augmentation device on allograft reconstructions for chronic ruptures of the anterior cruciate ligament. AB - A prospective study was performed to determine the effect of a combination of a ligament-augmentation device with a bone-patellar ligament-bone allograft for the treatment of chronic rupture of the anterior cruciate ligament. One hundred and fifteen knees in 110 patients were divided into two groups. Group BLB consisted of sixty-six knees in sixty-four patients who were managed with a bone-patellar ligament-bone allograft only, and Group BLB-LAD consisted of forty-nine knees in forty-six patients who were managed with both the allograft and a ligament augmentation device. Preoperatively, there were no statistically significant differences between the two groups with regard to fifteen variables. All patients were managed with the same postoperative program of immediate motion and rehabilitation of the knee. All patients returned for evaluation at a mean of thirty-four months (range, twenty-three to fifty-three months) postoperatively. The results were evaluated with a comprehensive rating system that assessed twenty factors. Both of these procedures significantly decreased functional limitations and symptoms and improved the level of sports activity and the over all score. However, the use of the ligament-augmentation device did not improve the efficacy of the reconstruction with regard to any of the individual variables that were assessed or in terms of the over-all score. All but one of the patients regained an arc of 0 to 135 degrees of motion. Although the augmentation device reduced anterior-posterior displacement effectively for the first twenty weeks postoperatively (p less than 0.05), there was no difference between the groups in terms of the percentage of knees that had abnormal displacement at the latest follow-up. A new classification system was developed to determine rates of failure. The over-all rate of failure was 28 per cent (thirty-two) of the 115 knees: 29 per cent (nineteen) of the sixty-six knees in Group BLB and 27 per cent (thirteen) of the forty-nine knees in Group BLB-LAD. The difference between the two groups was not statistically significant. The addition of the ligament augmentation device did not improve the results of allograft reconstruction in the treatment of chronic rupture of the anterior cruciate ligament. The use of either an allograft alone or an allograft combined with a ligament-augmentation device did not reduce the amount of anterior-posterior displacement satisfactorily in all of the knees. PMID- 1522104 TI - Use of a semitendinosus tendon autogenous graft for rupture of the patellar ligament after total knee arthroplasty. A report of seven cases. PMID- 1522105 TI - Posterior stabilized prosthesis. Results after follow-up of nine to twelve years. AB - We reviewed, nine to twelve years postoperatively, the records on an original cohort of 289 arthroplasties (218 patients) in which a posterior stabilized knee prosthesis with an all-polyethylene tibial component had been inserted at The Hospital for Special Surgery. One hundred and eighty intact prostheses in 139 patients were available for this analysis. Fourteen knees in fourteen patients had had a revision procedure. Five of these fourteen patients had had a bilateral arthroplasty, but only one knee of each of the five patients had been revised. Forty-eight of the patients (sixty-six knees) had died less than nine years after the operation. Twenty-nine other knees (twenty-two patients) had been lost to follow-up before a nine-year evaluation could be performed. Considering all 194 knees (including the fourteen that had been revised), the result with the system of The Hospital for Special Surgery was excellent for 117 knees (61 per cent), good for fifty-one (26 per cent), fair for twelve (6 per cent), and poor for the fourteen knees (7 per cent) that had been revised. The 180 knees in which the prosthesis was intact were also rated with the new scoring system of The Knee Society: the average postoperative knee score was 92 points (range, 35 to 100 points), and the average score for function was 66 points (range, 0 to 100 points). Survivorship analysis showed that the average annual rate of failure was 0.4 per cent and that the over-all rate of success at thirteen years was 94 per cent.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1522106 TI - Revision of the acetabular component with an uncemented Harris-Galante porous coated prosthesis. AB - One hundred and forty revisions for loosening of the acetabular component were performed in 124 patients, with the use of an uncemented Harris-Galante acetabular prosthesis. A component was considered loose if there was a change in its position or vertical or horizontal migration, or both, of four millimeters or more, as demonstrated on serial radiographs. All patients were followed prospectively for a mean of forty-one months (range, twenty-four to seventy-six months). Bone-grafting was performed at the time of the revision in 127 of the hips. Identifiable failure of fixation of the acetabular component occurred in only two hips (1 per cent), which had both severe acetabular bone loss and pelvic discontinuity. In one of these hips, fixation of the component could not be achieved during the revision, and the component subsequently migrated. No other components migrated. Only one patient had a revision of the index acetabular operation. A continuous radiolucency developed at the bone-mesh interface of five acetabular components, and in one other hip a small portion of the mesh separated. This hip was reoperated on for a problem with the femur, and the socket was found to be rigidly fixed. No other evidence of loosening was identified. All of the bone grafts united, but partial resorption of the graft occurred in thirty-nine hips. Although there were substantial osseous defects that necessitated major bone-grafting, revision with the uncemented Harris Galante porous-coated acetabular component provided superior fixation compared with that reported in other series in which cemented acetabular components were used for revision. Of the 140 hips, eighty-nine (64 per cent) had a postoperative score of good or excellent, according to the Harris hip-rating system. Twenty eight (70 per cent) of the forty hips that had revision of the acetabular component alone were rated as good or excellent. PMID- 1522107 TI - A cap binding protein that may mediate nuclear export of RNA polymerase II transcribed RNAs. AB - It has previously been shown that efficient export of U1 snRNA or of microinjected, in vitro synthesized, RNA transcripts from the nucleus of Xenopus oocytes is facilitated by their monomethyl guanosine cap structures. Nuclear exit of these transcripts could be competitively inhibited by microinjection of an excess of a cap analog, the dinucleotide m7GpppG (Hamm, J., and I. W. Mattaj. 1990. Cell. 63:109-118). We have now analyzed the ability of several other related cap analogs to inhibit the export of U1 snRNA from the nucleus. The results define the recognition specificity of a factor(s) involved in RNA transport, and indicate that the cap binding activity (CBA) involved in RNA export is different from cap binding proteins (CBPs) involved in the initiation of translation. A CBP, whose specificity for different analogs correlates with the ability of the analogs to inhibit U1 snRNA export, is identified in nuclear extracts prepared from HeLa cells. We propose that this protein may have a role in the export of capped RNAs from the nucleus. PMID- 1522108 TI - In vitro assembly of prenucleolar bodies in Xenopus egg extract. AB - Nuclei assembled in Xenopus egg extract from purified DNA or chromatin resemble their natural counterparts in a number of structural and functional features. However, the most obvious structural element of normal interphase nuclei, the nucleolus, is absent from the in vitro reconstituted nuclei. By EM, cytological silver staining, and immunofluorescence microscopy employing antibodies directed against various nucleolar components we show that nuclei assembled in vitro contain numerous distinct aggregates that resemble prenucleolar bodies (PNBs) by several criteria. Formation of these PNB-like structures requires pore complex mediated nuclear transport of proteins but is independent of the genetic content of the in vitro nuclei as well as transcriptional and translational events. Our data indicate that nuclei assembled in vitro are capable of initiating early steps of nucleologenesis but that the resulting PNBs are unable to fuse with each other, probably due to the absence of a functional nucleolus organizer. With appropriate modifications, this experimental system should be useful to define and analyze conditions promoting the site-specific assembly of PNBs into a coherent nucleolar body. PMID- 1522109 TI - Hepatitis B surface antigen assembles in a post-ER, pre-Golgi compartment. AB - Expression of hepatitis B surface antigen (HBsAg), the major envelope protein of the virus, in the absence of other viral proteins leads to its secretion as oligomers in the form of disk-like or tubular lipoprotein particles. The observation that these lipoprotein particles are heavily disulphide crosslinked is paradoxical since HBsAg assembly is classically believed to occur in the ER, and hence in the presence of high levels of protein disulphide isomerase (PDI) which should resolve these higher intermolecular crosslinks. Indeed, incubation of mature, highly disulphide crosslinked HBsAg with recombinant PDI causes the disassembly of HBsAg to dimers. We have used antibodies against resident ER proteins in double immunofluorescence studies to study the stages of the conversion of the HBsAg from individual protein subunits to the secreted, crosslinked, oligomer. We show that HBsAg is rapidly sorted to a post-ER, pre Golgi compartment which excludes PDI and other major soluble resident ER proteins although it overlaps with the distribution of rab2, an established marker of an intermediate compartment. Kinetic studies showed that disulphide-linked HBsAg dimers began to form during a short (2 min) pulse, increased in concentration to peak at 60 min, and then decreased as the dimers were crosslinked to form higher oligomers. These higher oligomers are the latest identifiable intracellular form of HBsAg before its secretion (t 1/2 = 2 h). Brefeldin A treatment does not alter the localization of HBsAg in this PDI excluding compartment, however, it blocks the formation of new oligomers causing the accumulation of dimeric HBsAg. Hence this oligomerization must occur in a pre-Golgi compartment. These data support a model in which rapid dimer formation, catalyzed by PDI, occurs in the ER, and is followed by transport of dimers to a pre-Golgi compartment where the absence of PDI and a different lumenal environment allow the assembly process to be completed. PMID- 1522110 TI - The activity of Golgi transport vesicles depends on the presence of the N ethylmaleimide-sensitive factor (NSF) and a soluble NSF attachment protein (alpha SNAP) during vesicle formation. AB - An assay designed to measure the formation of functional transport vesicles was constructed by modifying a cell-free assay for protein transport between compartments of the Golgi (Balch, W. E., W. G. Dunphy, W. A. Braell, and J. E. Rothman. 1984. Cell. 39:405-416). A 35-kD cytosolic protein that is immunologically and functionally indistinguishable from alpha SNAP (soluble NSF attachment protein) was found to be required during vesicle formation. SNAP, together with the N-ethylmaleimide-sensitive factor (NSF) have previously been implicated in the attachment and/or fusion of vesicles with their target membrane. We show that NSF is also required during the formation of functional vesicles. Strikingly, we found that after vesicle formation, the NEM-sensitive function of NSF was no longer required for transport to proceed through the ensuing steps of vesicle attachment and fusion. In contrast to these functional tests of vesicle formation, SNAP was not required for the morphological appearance of vesicular structures on the Golgi membranes. If SNAP and NSF have a direct role in transport vesicle attachment and/or fusion, as previously suggested, these results indicate that these proteins become incorporated into the vesicle membranes during vesicle formation and are brought to the fusion site on the transport vesicles. PMID- 1522111 TI - Pathways of internalization of the hCG/LH receptor: immunoelectron microscopic studies in Leydig cells and transfected L-cells. AB - Monoclonal anti-receptor antibodies were used to study the cellular traffic of the hCG/LH receptor by immunoelectron microscopy. The LHR38 antibody was shown to bind to the extracellular domain of the receptor but not to interfere with hormone binding, adenylate cyclase activation or with the rate of internalization of the receptor. Pig Leydig cells and a permanent L-cell line expressing the LH receptor were used for the study. Incubation with LHR38-gold complexes showed the LH receptors to be randomly distributed over the cell surface including the clathrin coated pits. The LH receptors were internalized via a route including coated pits, coated vesicles and multivesicular bodies to lysosomes. This route is different from that observed for beta-adrenergic, muscarinic, and yeast mating factor receptors and considered previously as possibly general for G-protein coupled receptors. The use of [125I]LHR38 allowed precise measurement of the rate of internalization, showing the existence of a constitutive pathway which was increased 11-fold by hormone administration. Double labeling experiments suggested that the hormone (hCG-Au15nm) and the receptor (labeled with LHR38 Au5nm) have similar routes of endocytosis, both of them being degraded in lysosomes. Studies of the reappearance of LHR38-Au5nm on the surface of the cells and the use of monensin indicated that only a very small proportion of the receptor molecules were recycled to the cell surface. The distribution and the intracellular pathways of LH receptors are very similar in Leydig cells and transfected L-cells. This opens the possibility of using the latter to study, by in vitro mutagenesis, the molecular mechanisms involved in the cellular traffic of LH receptors. PMID- 1522112 TI - Clathrin heavy chain is required for pinocytosis, the presence of large vacuoles, and development in Dictyostelium. AB - To investigate the intracellular role of the clathrin heavy chain in living cells, we have used "antisense" RNA to engineer mutant Dictyostelium discoideum cells that are severely deficient in clathrin heavy chain expression. Immunoblots stained with an anti-clathrin heavy chain antiserum revealed that mutant cells contained undetectable amounts of clathrin heavy chain protein. Similarly, Northern blots showed an absence of clathrin heavy chain mRNA. Clathrin heavy chain-deficient Dictyostelium cells were viable, but exhibited growth rates twofold slower than parental cells. Whereas many morphological features of the mutant cells were normal, mutant cells lacked coated pits and coated vesicles. Clathrin-deficient cells were also missing large translucent vacuoles that serve as endosomes and contractile vacuoles. In the absence of clathrin heavy chain, mutant cells displayed three distinct functional defects: (a) impairment in endocytosis of fluid phase markers, but competence in another endocytic pathway, the phagocytosis of solid particles; (b) defects in osmoregulation; and (c) inability to complete the starvation-induced development cycle. PMID- 1522113 TI - The 27-kD diphtheria toxin receptor-associated protein (DRAP27) from vero cells is the monkey homologue of human CD9 antigen: expression of DRAP27 elevates the number of diphtheria toxin receptors on toxin-sensitive cells. AB - Diphtheria toxin (DT) receptor associates with a 27-kD membrane protein (DRAP27) in monkey Vero cells. A cDNA encoding DRAP27 was isolated, and its nucleotide sequence was determined. The deduced amino acid sequence revealed that DRAP27 is the monkey homologue of human CD9 antigen. DRAP27 is recognized by CD9 antibodies. A human-mouse hybrid cell line (3279-10) possessing human chromosome 5, sensitive to DT, but not expressing CD9 antigen, was used for transfection experiments with DRAP27. When the cloned cDNA encoding DRAP27 was transiently expressed in 3279-10 cells, the total DT binding capacity was three to four times higher than that of untransfected controls. Transfectants stably expressing DRAP27 have an increased number of DT binding sites on the cell surface. Furthermore, the transfectants are 3-25 times more sensitive to DT than untransfected cells, and the sensitivity of these cells to DT is correlated with the number of DRAP27 molecules on the surface. However, when the cloned cDNA was introduced into mouse cell lines that do not express DT receptors, neither an increased DT binding nor enhancement of DT sensitivity was observed. Hence, we conclude that DRAP27 itself does not bind DT, but serves to increase DT binding and consequently enhances DT sensitivity of cells that have DT receptors. 12 proteins related to DRAP27/CD9 antigen were found through homology search analysis. These proteins appear to belong to a new family of transmembrane proteins. PMID- 1522114 TI - Localization of dystrophin COOH-terminal domain by the fracture-label technique. AB - The precise localization of dystrophin in the skeletal muscle cell should contribute to a better understanding of the yet unclear functional role of this protein, both in normal and in Duchenne muscular dystrophy. Immunocytochemical studies did not give conclusive results on the localization of dystrophin with respect to the sarcolemma and to the cytoskeletal components. To improve the reliability of the electron microscopic immunocytochemical localization of dystrophin, a mAb against the COOH-terminus of the molecule has been used in association with the fracture-label technique, which, causing a partition of the membrane in protoplasmic and exoplasmic halves, allows a more precise dystrophin localization. The results obtained indicate that dystrophin is associated with the protoplasmic half of the plasmalemma, and the observation that it does not randomly follow the partition of the membrane is consistent with a stable association with the cytoskeleton. PMID- 1522115 TI - Costameres are sites of force transmission to the substratum in adult rat cardiomyocytes. AB - Costameres, the vinculin-rich, sub-membranous transverse ribs found in many skeletal and cardiac muscle cells (Pardo, J. V., J. D. Siciliano, and S. W. Craig. 1983. Proc. Natl. Acad. Sci. USA. 80:363-367.) are thought to anchor the Z lines of the myofibrils to the sarcolemma. In addition, it has been postulated that costameres provide mechanical linkage between the cells' internal contractile machinery and the extracellular matrix, but direct evidence for this supposition has been lacking. By combining the flexible silicone rubber substratum technique (Harris, A. K., P. Wild, and D. Stopak. 1980. Science (Wash. DC). 208:177-179.) with the microinjection of fluorescently labeled vinculin and alpha-actinin, we have been able to correlate the distribution of costameres in adult rat cardiac myocytes with the pattern of forces these cells exert on the flexible substratum. In addition, we used interference reflection microscopy to identify areas of the cells which are in close contact to the underlying substratum. Our results indicate that, in older cell cultures, costameres can transmit forces to the extracellular environment. We base this conclusion on the following observations: (a) adult rat heart cells, cultured on the silicone rubber substratum for 8 or more days, produce pleat-like wrinkles during contraction, which diminish or disappear during relaxation; (b) the pleat-like wrinkles form between adjacent alpha-actinin-positive Z-lines; (c) the presence of pleat-like wrinkles is always associated with a periodic, "costameric" distribution of vinculin in the areas where the pleats form; and (d) a banded or periodic pattern of dark gray or close contacts (as determined by interference reflection microscopy) has been observed in many cells which have been in culture for eight or more days, and these close contacts contain vinculin. A surprising finding is that vinculin can be found in a costameric pattern in cells which are contracting, but not producing pleat-like wrinkles in the substratum. This suggests that additional proteins or posttranslational modifications of known costamere proteins are necessary to form a continuous linkage between the myofibrils and the extracellular matrix. These results confirm the hypothesis that costameres mechanically link the myofibrils to the extracellular matrix. We put forth the hypothesis that costameres are composite structures, made up of many protein components; some of these components function primarily to anchor myofibrils to the sarcolemma, while others form transmembrane linkages to the extracellular matrix. PMID- 1522116 TI - The lymphocyte-specific protein LSP1 binds to F-actin and to the cytoskeleton through its COOH-terminal basic domain. AB - The lymphocyte-specific phosphoprotein LSP1 associates with the cytoplasmic face of the plasma membrane and with the cytoskeleton. Mouse LSP1 protein contains 330 amino acids and contains an NH2-terminal acidic domain of approximately 177 amino acids. The COOH-terminal half of the LSP1 protein is rich in basic residues. In this paper we show that LSP1 protein which is immunoprecipitated with anti-LSP1 antibodies from NP-40-soluble lysates of the mouse B-lymphoma cell line BAL17 is associated with actin. In vitro binding experiments using recombinant LSP1 (rLSP1) protein and rabbit skeletal muscle actin show that LSP1 binds along the sides of F-actin but does not bind to G-actin. rLSP1 does not alter the initial polymerization kinetics of actin. The highly conserved COOH-terminal basic domains of mouse and human LSP1 share a significant homology with the 20-kD COOH terminal F-actin binding fragment of caldesmon. A truncated rLSP1 protein containing the entire COOH-terminal basic domain from residue 179 to 330, but not the NH2-terminal acidic domain binds to F-actin at least as well as rLSP1. When LSP1/CAT fusion proteins are expressed in a LSP1-negative T-lymphoma cell line, only fusion proteins containing the basic COOH-terminal domain associate with the NP-40-insoluble cytoskeleton. These data show that LSP1 binds F-actin through its COOH-terminal basic domain and strongly suggest that LSP1 interacts with the cytoskeleton by direct binding to F-actin. We propose that LSP1 plays a role in mediating cytoskeleton driven responses in lymphocytes such as receptor capping, cell motility, or cell-cell interactions. PMID- 1522117 TI - The two major membrane skeletal proteins (articulins) of Euglena gracilis define a novel class of cytoskeletal proteins. AB - 60% of the peripheral membrane skeleton of Euglena gracilis consists of equimolar amounts of two proteins (articulins) with M(r)s in SDS gels of 80 and 86 kD. To understand eventually how these proteins assemble and function in maintaining cell form and membrane integrity we have undertaken a molecular characterization of articulins. A lambda gt11 expression library constructed from Euglena gracilis mRNAs was screened with antibodies against both articulins. Two sets of cDNAs were recovered, and evidence from three independent assays confirmed that both sets encoded articulins: (a) Anti-articulin antibodies recognized a high molecular weight beta-galactosidase (beta-gal) fusion protein expressed in bacteria infected with lambda gt11 cDNA clones. (b) Antibodies generated against the bacterially expressed beta-gal fusion protein identified one or the other articulin in Western blots of Euglena proteins. These antibodies also localized to the membrane skeletal region in thin sections of Euglena. (c) Peptide maps of the beta-gal fusion protein were similar to peptide maps of Euglena articulins. From the nucleotide sequence of the two sets of cDNAs an open reading frame for each articulin was deduced. In addition to 37% amino acid identity and overall structural similarity, both articulins exhibited a long core domain consisting of over 30 12-amino acid repeats with the consensus VPVPV--V--. Homology plots comparing the same or different articulins revealed larger, less regular repeats in the core domain that coincided with predicted turns in extended beta-sheets. Outside the core domain a short hydrophobic region containing four seven-amino acid repeats (consensus: APVTYGA) was identified near the carboxy terminus of the 80-kD articulin, but near the amino terminus of the 86-kD articulin. No extensive sequence similarities were found between articulins and other protein sequences in various databanks. We conclude that the two articulins are related members of a new class of membrane cytoskeletal proteins. PMID- 1522118 TI - Identification of an epithelial protein related to the desmosome and intermediate filament network. AB - Using a mAb, referred to as 08L, we have identified a protein, of M(r) approximately 140,000, associated with desmosomes of epithelial cells. The 08L antibody stained the intracellular side of lateral cell margins of monolayer epithelial cells but did not stain cell margins free of cell contact. Immunoelectron microscopy revealed that the 08L antigen was localized to the cytosolic surface of the desmosomal plaque near points of intermediate filament convergence with apparently little staining of the desmosomal plaque proper. Western blots revealed the 08L antigen to be a protein, of M(r) approximately 140,000, found in the Triton-X 100 insoluble pellet. High salt-containing buffers extracted the 08L antigen from the insoluble material. Examination of the assembly of 08L to the desmosome complex, in cells grown in low confluent culture or in calcium-switch assays, by double immunofluorescence with 08L and anti desmoplakin antibody, revealed that 08L was recruited to morphologically identifiable desmosomes. 08L antigen may exist in a cytosolic pool prior to assembly to the cell surface. The solubility of 08L in low calcium and normal calcium conditions, however, was similar. 08L association to the desmosome was correlated with increased organization of the intermediate filament network. We suggest that the 08L antigen may be involved in the organization and stabilization of the desmosome-IF complexes of epithelia. PMID- 1522119 TI - Serum response factor p67SRF is expressed and required during myogenic differentiation of both mouse C2 and rat L6 muscle cell lines. AB - The 67-kD serum response factor (p67SRF) is a ubiquitous nuclear transcription factor that acts by direct binding to a consensus DNA sequence, the serum response element (SRE), present in the promoter region of numerous genes. Although p67SRF was initially implicated in the activation of mitogen-stimulated genes, the identification of a sequence similar to SRE, the CArG box motif, competent to interact with SRE binding factors in many muscle-specific genes, has led to speculation that, in addition to its function in cell proliferation, p67SRF may play a role in muscle differentiation. Indirect immunofluorescence using affinity-purified antibodies specifically directed against p67SRF reveals that this factor is constitutively expressed and localized in the nucleus of two skeletal muscle cell lines: rat L6 and mouse C2 myogenic cells during myogenic differentiation. This result was further confirmed through immunoblotting and Northern blot analysis. Furthermore, specific inhibition of p67SRF in vivo through microinjection of purified p67SRF antibodies prevented the myoblast myotube transition and the expression of muscle-specific genes such as the protein troponin T. We further showed that anti-p67SRF injection also inhibited the expression of the myogenic factor myogenin, implying an early requirement for p67SRF in muscle differentiation. These results demonstrate that p67SRF is involved in the process of skeletal muscle differentiation. The potential action of p67SRF via CArG sequences is discussed. PMID- 1522120 TI - Calcium/calmodulin transduces thrombin-stimulated secretion: studies in intact and minimally permeabilized human umbilical vein endothelial cells. AB - Thrombin stimulates cultured endothelial cells (EC) to secrete stored von Willebrand factor (vWF), but the signal transduction pathways are poorly defined. Thrombin is known to elevate the concentration of intracellular calcium ([Ca2+]i) and to activate protein kinase C (PKC) in EC. Since both calcium ionophores and phorbol esters release vWF, both second messenger pathways have been postulated to participate in vWF secretion in response to naturally occurring agonists. We find that in intact human EC, vWF secretion stimulated by either thrombin or by a thrombin receptor activating peptide, TR(42-55), can be correlated with agonist induced elevations of [Ca2+]i. Further evidence implicating calcium in the signal transduction pathway is suggested by the finding that MAPTAM, a cell-permeant calcium chelator, in combination with the extracellular calcium chelator EGTA, can inhibit thrombin-stimulated secretion. In contrast, the observation that staurosporine (a pharmacological inhibitor of PKC) blocks phorbol ester- but not thrombin-stimulated secretion provides evidence against PKC-mediated signal transduction. To examine further the signal transduction pathway initiated by thrombin, we developed novel conditions for minimal permeabilization of EC with saponin (4-8 micrograms/ml for 5-15 min at 37 degrees C) which allow the introduction of small extracellular molecules without the loss of large intracellular proteins and which retain thrombin-stimulated secretion. These minimally permeabilized cells secrete vWF in response to exogenous calcium, and EGTA blocks thrombin-induced secretion. Moreover, in these cells, thrombin stimulated secretion is blocked by a calmodulin-binding inhibitory peptide but not by a PKC inhibitory peptide. Taken together, these findings demonstrate that thrombin-stimulated vWF secretion is transduced by a rise in [Ca2+]i and provide the first evidence for the role of calmodulin in this process. PMID- 1522121 TI - A novel endothelial-specific membrane protein is a marker of cell-cell contacts. AB - mAbs were raised in mice against cultured human endothelial cells (EC) and screened by indirect immunofluorescence for their ability to stain intercellular contacts. One mAb denoted 7B4 was identified which, out of many cultured cell types, specifically decorated cultured human EC. The antigen recognized by mAb 7B4 is bound at the appositional surfaces of cultured EC only as they become confluent and is stably expressed at intercellular boundaries of confluent monolayers. EC recognition specificity was maintained when the antibody was assayed by immuno-histochemistry in tissue sections of many normal and malignant tissues and in blood vessels of different size and type. The antigen recognized by 7B4 was enriched at EC intercellular boundaries similarly in vitro and in situ. In vitro, addition of mAb 7B4 to confluent EC increased permeation of macromolecules across monolayers even without any obvious changes of cell morphology. In addition, when EC permeability was increased by agents such as thrombin, elastase, and TNF/gamma IFN, its distribution pattern at intercellular contact rims was severely altered. mAb 7B4 immunoprecipitated a major protein of 140 kD from metabolically and surface-labeled cultured EC extracts which appeared to be an integral membrane glycoprotein. On the basis of its distribution in cultured cells and in tissues in situ, 7B4 antigen is distinct from other described EC proteins enriched at intercellular contacts. NH2-terminal sequencing of the antigen, immunopurified from human placenta, and sequencing of peptides from tryptic peptide maps revealed identity to the cDNA deduced sequence of a recently identified new member of the cadherin family (Suzuki, S., K. Sano, and H. Tanihara. 1991. Cell Regul. 2:261-270.) These data indicate that 7B4 antigen is an endothelial-specific cadherin that plays a role in the organization of lateral endothelial junctions and in the control of permeability properties of vascular endothelium. PMID- 1522122 TI - Regulation of cell substrate adhesion: effects of small galactosaminoglycan containing proteoglycans. AB - Cell adhesion is a process which is initiated by the attachment of cells to specific sites in adhesive matrix proteins via cell surface receptors of the integrin family. This is followed by a reorganization of cytoskeletal elements which results in cell spreading and the formation of focal adhesion plaques. We have examined the effects of a class of small galactosaminoglycan-containing proteoglycans on the various stages of cell adhesion to fibronectin-coated substrates. Our results indicate that dermatan sulfate proteoglycans (DSPGs) derived from cartilage, as well as other related small proteoglycans, inhibit the initial attachment of CHO cells and rat embryo fibroblasts to substrates composed of the 105-kD cell-binding fibronectin fragment, but do not affect cell attachment to intact fibronectin. Although this effect involves binding of DSPGs to the substrate via the protein core, the intact proteoglycan is necessary for the observed activity. Isolated core proteins are inactive. The structural composition of the galactosaminoglycan chain does not appear to be functionally significant since both chondroitin sulfate and various dermatan sulfate proteoglycans of this family inhibit cell attachment to the fibronectin fragment. Neither the percentage of cells spread nor the mean area of spread cells adhering to substrates of intact fibronectin was significantly affected by the DSPGs. However, significantly fewer cells formed focal adhesions in the presence of DSPGs as compared with untreated control cells. These results suggest that the binding of small galactosaminoglycan-containing proteoglycans to a fibronectin substrate may affect several stages in the cell adhesion process. PMID- 1522123 TI - Interleukin 6 promotes epithelial migration by a fibronectin-dependent mechanism. AB - We investigated the effect of interleukin 6 (IL-6) on the migration of rabbit corneal epithelium in vitro and on the attachment of dissociated corneal epithelial cells to a fibronectin matrix. When corneal blocks were cultured with IL-6 for 24 hours, the length of the path of epithelial migration over exposed corneal stroma increased significantly (p less than 0.005 at the concentration of 10 ng/ml) in proportion to the concentrations of IL-6 (0.1-10.0 ng/ml). The addition of antiserum against fibronectin or of GRGDSP abolished the stimulatory effect of IL-6 on epithelial migration. When corneal epithelial cells were cultured with various concentrations of IL-6, suspended, and plated on wells coated with fibronectin (10 micrograms/ml), the number of cells attached to the wells increased in a dose-dependent manner. The presence of antibody against fibronectin or of GRGDSP during the attachment assay decreased the number of cells attached to the fibronectin matrix, regardless of the fact that the cells had been cultured with IL-6 or not. IL-6 stimulated the attachment of corneal epithelial cells to collagen type IV and to laminin matrices. However, the presence of GRGDSP did not affect the cell attachment to collagen type IV and to laminin. These findings strongly indicate that IL-6 stimulates epithelial migration in the cornea by a fibronectin-dependent mechanism, presumably the increased expression of fibronectin receptors. PMID- 1522124 TI - Heparin inhibition of autonomous growth implicates amphiregulin as an autocrine growth factor for normal human mammary epithelial cells. AB - Normal human mammary epithelial cells (HMECs) proliferate in a serum-free defined growth medium in the absence of epidermal growth factor (Li and Shipley, 1991). Amphiregulin (AR) is a heparin-regulated, EGF-like growth factor. Our observation that one strain of HMECs produce AR mRNA (Cook et al., 1991 a) stimulated us to determine whether AR expression was a common phenomenon in HMECs and whether AR could act as an autocrine growth factor to support the EGF-independent growth of these cells. In this study, we detected high levels of AR expression in four separate HMEC strains while one immortal mammary cell line (HBL-100) and six mammary tumor-derived cell lines had low to undetectable levels of AR. The EGF independent growth of HMECs was blocked by the addition of heparin or a monoclonal anti-EGF receptor antibody to the culture medium, implicating AR as an autocrine growth mediator. This hypothesis is further supported by the fact that medium conditioned by HMECs contains secreted AR protein. A mammary tumor-derived cell line, Hs578T, which proliferates in an EGF-independent manner, does not express detectable levels of AR and is not growth inhibited by heparin. Examination of the same cell types for expression of transforming growth factor type-alpha (TGF-alpha) mRNA revealed coordinate expression of AR and TGF-alpha in these cells. These data suggest that both AR and TGF-alpha mRNA are produced in much greater abundance by normal HMECs than in tumor-derived cells in culture, and that AR is an important autostimulatory factor for the growth of normal HMECs. PMID- 1522125 TI - Apoptosis of murine BW 5147 thymoma cells induced by cold shock. AB - Exposure of thymoma BW 5147 cells to cold (0-2 degrees C) followed by rewarming at 37 degrees C (cold shock) resulted in internucleosomal DNA cleavage. Sensitivity to cold shock-induced cell death was critically dependent on the serum concentration in the medium and limited to serum-deficient medium (2% serum concentration), whereas cells in the complete growth medium (10%) were completely resistant. RNA/protein-synthesis inhibitors (cycloheximide and actinomycin D) had no effect on cold shock-induced DNA cleavage in BW 5147 cells. The DNA fragmentation seems to be independent of increase in the cytosolic Ca2+ level. Moreover, reduction in the calcium content of the external medium by EGTA induced DNA cleavage. Incubation of BW 5147 cells in the presence of colchicine and cytochalasin B led to the apoptosis. The latter suggests that the internucleosomal DNA cleavage induced by cold shock may be concerned with the disruption of some cytoskeletal network caused by cooling. The results are discussed in relation to cell proliferation. PMID- 1522126 TI - Differential modulation of vascular cell integrin and extracellular matrix expression in vitro by TGF-beta 1 correlates with reciprocal effects on cell migration. AB - In vitro, BAEC and BASMC migratory phenotypes are known to be reciprocally modulated by both soluble factors and extracellular matrix proteins. In addition, integrin matrix receptors mediate endothelial and smooth muscle cell attachment and migration. To further elucidate these phenomena, we studied the effects of TGF-beta 1 on integrin expression by vascular BASMC and BAEC in tissue culture. TGF-beta 1 upregulated mRNA levels and surface pools of BASMC beta 3 integrin classes without modulating beta 1 integrin mRNA levels or expression of beta 1 integrin organization. In contrast to its effects on BASMC, TGF-beta 1 increased BAEC mRNA levels and surface expression of beta 1 and beta 3 integrins without altering their organization. Conversely, extracellular matrix components (fibronectin, laminin, and fibrinogen) organized cell surface integrins in both BASMC and BAEC without affecting the size of their cell surface pools. These data are consistent with the hypothesis that SMC and EC behavior in neointimal lesions may be modulated, in part, through a coordination of soluble factor and extracellular matrix protein regulation of integrin surface expression and organization. PMID- 1522127 TI - Plasminogen activator inhibitor-1 is induced in migrating endothelial cells. AB - It has been proposed that a finely tuned protease-anti-protease equilibrium must be maintained during processes of cell migration in order to limit extracellular proteolysis to the close proximity of the cell surface, and thereby to prevent excessive extracellular matrix degradation. We have previously shown that urokinase-type plasminogen activator (u-PA) activity is induced in microvascular endothelial cells migrating from the edges of a wounded monolayer in vitro (Pepper et al., J. Cell Biol., 105:2535-2541, 1987). By Northern analysis, we now demonstrate that plasminogen activator inhibitor 1 (PAI-1) mRNA is increased in multiple-wounded monolayers of bovine microvascular (BME) or aortic (BAE) endothelial cells, with a maximal 7- and 9-fold increase 4 h after wounding, respectively. By in situ hybridization, we demonstrate that the increase in PAI-1 mRNA is localized to cells at the edge of a wounded BME or BAE cell monolayer. The increase in PAI-1 mRNA observed in BME cells is independent of cell division and is inhibited by antibodies to basic fibroblast growth factor (bFGF), suggesting that PAI-1 induction in migrating cells is mediated by the autocrine activity of bFGF. Taken together with our previous observations on the induction of u-PA, these results support the hypothesis that the proteolytic balance in the pericellular environment of migrating cells is regulated through the concomitant production of proteases and protease inhibitors. PMID- 1522128 TI - Regulation of cell proliferation: late down-regulation of c-myb preceding myelo monocytic cell differentiation. AB - Expression of the c-myb nuclear oncogene during the cell proliferation and differentiation of HL-60 human promyelocytic leukemia cells was characterized and compared to the expression of c-fos, another nuclear oncogene with transcriptional regulatory activity. During progression through the cell cycle, the amount of c-myb protein increased. The increase was commensurate with total cell size, thus preserving the relative abundance of c-myb protein present at the onset of the cell cycle. In HL-60 cells, the induced metabolic cascade leading to terminal myeloid or monocytic differentiation segregates into two steps occurring over two division cycles. Expression of c-myb did not diverge from the control until late in this metabolic cascade when it declined prior to onset of terminal differentiation. This course of expression was similar for both the retinoic acid induced myeloid or the 1,25-dihydroxy vitamin D2 induced monocytic terminal differentiation of the cells. Bromodeoxyuridine, which induces proliferative arrest but not phenotypic differentiation of these cells, induced the same course of c-myb expression as the inducers of terminal differentiation. The same course of c-myb expression with growth arrest induced by these three different means is consistent with a potential proliferation regulatory role for c-myb in late but not early events leading to terminal differentiation. The dynamics of c-myb expression during this process were qualitatively, but not quantitatively, similar to the course of c-fos expression. Thus, taken with previous results, then amongst the nuclear oncogenes or tumor suppressor genes, c-myc, RB, c-fos, and c-myb, only c-myc and RB expression exhibit early regulation during induced HL-60 cell differentiation. PMID- 1522129 TI - Use of peanut lectin and rat mammary stem cell lines to identify a cellular differentiation pathway for the alveolar cell in the rat mammary gland. AB - The presence of the carbohydrate receptor for PNL has been used to identify the previously described morphological types of epithelial cell produced as the stem cell line rat mammary 25 (Rama 25) differentiates to casein secretory alveolar like cells in vitro. Thus when cultures of the epithelial stem cell line Rama 25 are treated with neuraminidase, fluorescently-conjugated PNL fails to stain cuboidal cells, stains weakly grey cells, and stains strongly the surface of dark cells. When superconfluent cultures of Rama 25 are treated with dimethyl sulfoxide or retinoic acid and prolactin, estradiol, hydrocortisone, and insulin to induce differentiation to alveolar cells, PNL stains strongly the untreated surfaces of droplet cells and casein-secreting vacuolated cells. PNL-staining of the derivative cell lines with truncated cellular pathways, and quantitative binding of [125I]-labeled PNL to the cultured cells are consistent with this cellular staining pattern. The presence of the carbohydrate receptor for peanut lectin (PNL) has also been used to identify specific epithelial cell types in different mammary structures of the developing rat mammary gland, as they differentiate to casein secretory alveolar cells in vivo. Thus when different structures of the developing rat mammary gland are treated with neuraminidase, peroxidase-conjugated PNL fails to stain histochemically the majority of epithelial cells in ducts, stains the cytoplasm of the majority of epithelial cells in terminal end-buds (TEBs), and stains strongly the luminal surfaces of the majority of epithelial cells in alveolar buds (ABs). PNL also stains the untreated luminal surfaces of alveolar cells, whether or not the cells can be stained with a monoclonal antibody to rat beta-casein. Stimulation of mammary differentiation by an analogue of ethyl retinoate or by perphenazine causes cells in end-buds to bind PNL without the necessity for their desialylation similar to that seen in casein secretory alveoli of lactating rats. In conclusion the different interconverting cell types of Rama 25 which form a pathway to casein secretory cells in vitro are thus equated with recognisable epithelial cell types in vivo. These results suggest that casein-secretory cells in vivo are generated by similar successive interconversions between the major epithelial cell types present in the different mammary structures in the order: ducts, TEBs, ABs, alveoli, and secretory alveoli. PMID- 1522130 TI - Calcium transport by sarcoplasmic reticulum of vascular smooth muscle: II. Effects of calmodulin and calmodulin inhibitors. AB - The role of calmodulin (CaM) in modulating calcium (Ca) uptake by sarcoplasmic reticulum (SR) of vascular smooth muscle was studied in saponin skinned strips of rat caudal artery. Exogenous CaM concentrations ranging from 0.3-1.8 microM did not statistically change the steady state MgATP-dependent Ca content, the MgATP independent Ca content, or the oxalate-stimulated Ca influx. Calmidazolium (CDZ), W-7, and trifluoperazine (TFP) were used to examine the potential effect of an endogenous CaM pool on inward Ca transport. The IC50 of these antagonists for inhibition of Ca-CaM-stimulated phosphodiesterase activity and Ca-activated superprecipitation of canine aortic actomyosin was measured and found to be in the low micromolar range with a rank order of potency for inhibition of CDZ greater than TFP greater than W-7. In skinned tissues, micromolar concentrations of antagonists that inhibited CaM-mediated reactions in isolated enzyme systems did not reduce Ca content or oxalate-stimulated Ca influx. At higher concentrations of 100-200 microM, the MgATP-dependent Ca content was significantly reduced by TFP and W-7 but not by CDZ. The order of potency for inhibition of Ca uptake was TFP greater than W-7 greater than CDZ. The MgATP independent Ca content was significantly decreased only by 200 microM TFP. Although none of these inhibitors significantly altered Ca efflux at concentrations up to 100 microM, Ca release was significantly stimulated by all three at 200 microM. The TFP-stimulated Ca release was partially inhibited by ruthenium red. The results indicate that neither exogenous CaM nor an endogenous CaM pool directly modulates inward Ca transport by the SR of saponin skinned caudal artery. The inhibition of Ca uptake produced by hundred micromolar concentrations of CaM antagonists fails to correlate with the order of and with the potency of inhibition measured in isolated enzyme systems. This suggests that the inhibition of Ca uptake produced by high concentrations of these antagonists may be independent of a specific interaction with CaM. The activation of Ca release by high concentrations of CaM antagonists may involve a nonspecific increase in membrane permeability as well as modulation of a membrane Ca channel. PMID- 1522131 TI - Potassium transport in nonpigmented epithelial cells of ocular ciliary body: inhibition of a Na+, K+, Cl- cotransporter by protein kinase C. AB - The mechanisms by which 86Rb+ (used as a tracer for K+) enters human nonpigmented ciliary epithelial cells were investigated. Ouabain-inhibitable bumetanide insensitive 86Rb+ transport accounted for approximately 70-80% of total, whereas bumetanide-inhibitable ouabain-insensitive uptake accounted for 15-25% of total. K+ channel blockers such as BaCl2 reduced uptake by approximately 5%. Bumetanide inhibited 86Rb+ uptake with an IC50 of 0.5 microM, while furosemide inhibited with an IC50 of about 20 microM. Bumetanide-inhibitable 86Rb+ uptake was reduced in Na(+)-free or Cl(-)-free media, suggesting that Na+ and Cl- were required for optimal uptake via this mechanism. These characteristics are consistent with a Na+, K+, Cl- cotransporter in NPE cells. Treatment of NPE cells for 15 min with phorbol 12-myristate, 13-acetate (PMA), an activator of protein kinase C, caused a 50-70% decrease in 86Rb+ uptake via the Na+, K+, Cl- cotransporter. Other 86Rb+ uptake mechanisms were not affected. 86Rb+ uptake via the Na+, K+, Cl- cotransporter could be inhibited by other phorbol esters and by dioctanoylglycerol, an analog of diacylglycerol, but not by 4 alpha phorbol didecanoate, an ineffective activator of protein kinase C. Staurosporine, a protein kinase C inhibitor, blocked phorbol ester inhibition of 86Rb+ uptake. These data suggest that a Na+, K+, Cl- cotransporter in NPE cells is inhibited by activation of protein kinase C. PMID- 1522132 TI - Electrogenic Na-independent HCO3 transport in OK cells. AB - We have shown previously that OK cells recover from an acid load in a medium nominally CO2-free by extruding H via a Na/H exchanger and a passive H-conductive pathway. In this work, the regulation of cell pH (pHi) was studied after addition or withdrawal of CO2/HCO3 (5% CO2, 95 mM HCO3, pH = 8) using the fluoroprobe BCECF. In the presence of Na and amiloride to inhibit Na/H exchange, the recovery of pHi after CO2 entry and CO2 exit were found to depend in part on HCO3 entry and exit, respectively. Efflux of H per se also contributed to restoring pHi after CO2 addition, whereas H influx may have played a smaller role to normalize pHi after CO2 removal. DIDS, 0.5 mM, significantly inhibited both recovery phases of pHi. Removal of Na failed to inhibit the recovery of pHi after CO2 addition and removal. Cl removal also failed to inhibit pHi recovery after CO2 removal. Cell depolarization in the presence of Na moderately stimulated the pHi recovery rate after CO2 addition whereas it markedly inhibited the normalization of pHi after CO2 removal. Cell depolarization in the absence of sodium had only a slight effect to increase pHi recovery after CO2 addition but markedly prevented the pHi recovery after CO2 removal. These results indicate that OK cells lack Na or Cl dependent HCO3 transport systems. The OK cell possesses a novel stilbene sensitive electrogenic HCO3 transport system that is involved in the regulation of cell pH. PMID- 1522133 TI - TGF-beta inhibits proliferation of and promotes differentiation of human promonocytic leukemia cells. AB - Transforming growth factor-beta 1 (TGF-beta 1) has been implicated in a variety of responses associated with wound healing and inflammation. Thus, TGF-beta 1 enhances production of several extracellular matrix proteins both in vitro and in vivo, is chemotactic for monocytes, and alters the functioning of lymphocytes. We have examined the ability of TGF-beta 1 to affect the behavior of human THP-1 promonocytic leukemia cells, a cell line with the capacity to differentiate into macrophage-like cells. TGF-beta 1 reduces the growth rate of these cells, induces morphologic changes, and promotes adherence to culture surfaces. In addition, the adherent cell population expresses high levels of esterase activity, acquires the ability to ingest latex beads, and releases elevated levels of interleukin 1. TGF beta 1-treated cells also express elevated levels of the beta 2 family of integrins. Taken together, these results suggest that TGF-beta 1 is capable of promoting the maturation of promonocytic cells into macrophages. This outcome has implications at wound sites where TGF-beta 1 and a myriad of other factors interact with many cell types to facilitate healing. PMID- 1522134 TI - Amnion cell biosynthesis of interleukin-8: regulation by inflammatory cytokines. AB - The cellular constituents of the placenta are important participants in the recruitment and trafficking of inflammatory cells within the placenta. In infection-induced labor, gestational tissues synthesize and release a variety of inflammatory cytokines whose effects include increased prostaglandin biosynthesis and the initiation of uterine contractions. Interleukin-8 (IL-8), a potent neutrophil chemoattractant, has been recently described as being elevated in the amniotic fluid of mothers with chorioamnionitis. We investigated the biosynthesis of IL-8 by human amnion cells and its regulation by other inflammatory cytokines. Cultured amnion cells obtained from normal term placentae were found to produce IL-8 in response to pathophysiologic concentrations of interleukin 1 beta (IL-1 beta) and tumor necrosis factor alpha (TNF-alpha). Treatment of amnion cells stimulated by IL-1 beta with cycloheximide resulted in increased IL-8 production, while incubation of IL-1 beta treated amnion cells with actinomycin D resulted in a concentration-dependent decrease in detectable amounts of IL-8. Northern blot analysis of cultured amnion cells stimulated with IL-1 beta demonstrated a rapid increase in IL-8 mRNA which peaked at 2-4 hr. These in vitro results suggest inflammation of gestational tissues in vivo may result in locally produced IL-8 and, in association with other inflammatory mediators, may be important in the pathophysiology of infection-induced labor. PMID- 1522135 TI - Proliferation-associated oxygen consumption and morphology of tumor cells in monolayer and spheroid culture. AB - The oxygen consumption rate, proliferative activity, and morphology of EMT6/Ro mouse mammary sarcoma cells in monolayer and multicellular spheroid culture have been investigated in a comparative study. During the transition of monolayer cells from the exponential into the plateau growth phase, there is a distinct decrease in the cellular volume that is associated with a corresponding decrease in the proliferative and respiratory activity of the cells. The decline in cell volume is mainly due to a decrease in the content of cytoplasm, whereas the size of the nucleus is only slightly reduced. A concomitant decrease in the number of mitochondria per cell obviously accounts for the reduction in cellular oxygen uptake. Despite a continuous decrease of cell proliferation from the surface to interior regions of EMT6 spheroids reflected by a gradient in tritiated thymidine labeling, volume-related oxygen consumption is rather uniform in viable regions of these aggregates. The finding can be explained by the results of the morphometric evaluation showing a uniform volume density of mitochondria, i.e., of oxygen-consuming sites within these spheroids. PMID- 1522136 TI - Protein kinase C phosphorylates caldesmon77 and vimentin and enhances albumin permeability across cultured bovine pulmonary artery endothelial cell monolayers. AB - Cytoskeletal protein (CSP) interactions are critical to the contractile response in muscle and non-muscle cells. Current concepts suggest that activation of the contractile apparatus occurs through selective phosphorylation by specific cellular kinase systems. Because the Ca(2+)-phospholipid-dependent protein kinase C (PKC) is involved in the regulation of a number of key endothelial cell responses, the hypothesis that PKC modulates endothelial cell contraction and monolayer permeability was tested. Phorbol myristate acetate (PMA), a direct PKC activator, and alpha-thrombin, a receptor-mediated agonist known to increase endothelial cell permeability, both induced rapid, dose-dependent activation and translocation of PKC in bovine pulmonary artery endothelial cells (BPAEC), as assessed by gamma-[32P]ATP phosphorylation of H1 histone in cellular fractions. This activation was temporally associated with evidence of agonist-mediated endothelial cell contraction as demonstrated by characteristic changes in cellular morphology. Agonist-induced activation of the contractile apparatus was associated with increases in BPAEC monolayer permeability to albumin (approximately 200% increase with 10(-6) MPMA, approximately 400% increase with 10(-8) M alpha-thrombin). To more closely examine the role of PKC in activation of the contractile apparatus, PKC-mediated phosphorylation of two specific CSPs, the actin- and calmodulin-binding protein, caldesmon77, and the intermediate filament protein, vimentin, was assessed. In vitro phosphorylation of both caldesmon and vimentin was demonstrated by addition of exogenous, purified BPAEC PKC to unstimulated BPAEC homogenates, to purified bovine platelet caldesmon77, or to purified smooth muscle caldesmon150. Caldesmon77 and vimentin phosphorylation were observed in intact [32P]-labeled BPAEC monolayers stimulated with either PMA or alpha-thrombin, as detected by immunoprecipitation. In addition, BPAEC pretreatment with the PKC inhibitor, staurosporine, prevented alpha-thrombin- and PMA-induced phosphorylation of both cytoskeletal proteins, attenuated morphologic evidence of contraction, and abolished agonist-induced barrier dysfunction. These results demonstrate that agonist-stimulated PKC activity results in cytoskeletal protein phosphorylation in BPAEC monolayer, an event which occurs in concert with agonist-mediated endothelial cell contraction and resultant barrier dysfunction. PMID- 1522138 TI - M-phase-promoting factor activation. PMID- 1522137 TI - Quantitative fatty acid analyses in cultured porcine pulmonary artery endothelial cells: the combined effects of fatty acid supplementation and oxidant exposure. AB - Supplemental fatty acids can modify the oxidant susceptibility of pulmonary artery endothelial cells (PAEC) in monolayer culture. In addition, in vivo dietary modifications have altered tissue and animal susceptibility to a variety of forms of oxidant stress. These modifications of oxidant injury have been attributed to changes in the numbers of fatty acid double bonds in cell lipids. We tested this hypothesis by incubating porcine PAEC in culture medium supplemented with either 0.1 mM oleic acid (18:1 omega 9) or with an equivalent volume of ethanol vehicle alone (ETOH-0.1%) for 3 h. After supplementation, PAEC were exposed to either oxidant stress, 100 microM hydrogen peroxide (H2O2) in Hanks' balanced salt solution (HBSS), or to control condition, HBSS alone, for 30 min. Supplemental PAEC were exposed to HBSS or H2O2 either immediately or 24, 48, or 72 h after supplementation. Supplementation with 18:1 protected PAEC from H2O2 induced injury at all time points. The fatty acid composition of PAEC phospholipid (PL), triglyceride (TG), and free fatty acid (FFA) subclasses was determined using thin layer and gas chromatography. The PL fraction contained the majority of PAEC fatty acids, and H2O2 reduced the polyunsaturates in this fraction regardless of supplementation. Supplementation with 18:1 increased the 18:1 content of PAEC PL, TG, and FFA at all time points, modified other fatty acids to a lesser extent, but failed to alter the overall number of fatty acid double bonds at all time points. These results indicate that modification of double bond number does not fully explain the mechanisms by which changes in lipid composition can modulate oxidant injury. PMID- 1522139 TI - Morphological and immuno-cytochemical characterization of a hetero-spheroid composed of fibroblasts and hepatocytes. AB - A novel method for the preparation of spheroids containing two types of cells (hetero-spheroid) has been successfully developed by utilizing a collagen conjugated thermo-responsive polymer, poly-N-isopropyl acrylamide (PNIPAAm), as a cell substratum. PNIPAAm solidifies above its lower critical solution temperature (LCST, about 30 degrees C), and instantly dissolves into the culture medium below its LCST. We firstly seeded and cultured human dermal fibroblasts on the substratum up to a confluent state and then seeded rat primary hepatocytes onto the fibroblast monolayer. The heterospheroid was prepared by detaching the hepatocyte-attached fibroblast monolayer at a temperature below LCST and culturing it on the non-adhesive substratum. The surface area of the substratum and the seeding population ratio of each cell precisely and reproducibly regulated the size and the cell composition of the resulting hetero-spheroid, respectively. Histological and immuno-cytochemical observations of spheroids revealed characteristic organizations of fibroblasts and hepatocytes within a spheroid because the latter cells expressed albumin for up to at least 3 weeks. TEM study of the hetero-spheroid showed the presence of structures morphologically similar to the Disse's space and the bile canaliculus, which are features characteristic of liver. These findings suggest that the method described above is useful for making a hetero-spheroid that morphologically and functionally resembles tissues or organs in vivo, i.e. an organoid. PMID- 1522140 TI - A method for determining the periodicity of a troponin component in isolated insect flight muscle thin filaments by gold/Fab labelling. AB - Insect flight muscle has a large component (Tn-H) in the tropomyosin-troponin complex that is not present in vertebrate striated muscle thin filaments. Tn-H is shown by gold/Fab labelling to be present at regular intervals in insect flight muscle thin filaments. The Fab fragment of a monoclonal antibody to Tn-H was conjugated directly with colloidal gold and this probe used to label isolated thin filaments from the flight muscle of Lethocerus indicus (water bug). The distribution of gold particles seen in electron microscope images of negatively stained thin filaments was analysed to show that the probe bound to sites having a periodicity of approximately 40 nm, which is the expected value for the tropomyosin-troponin repeat. Conjugates of Fab with colloidal gold particles of 3 nm diameter labelled almost all sites. Conjugates with gold particles of 5 nm and 10 nm diameter labelled less efficiently (70% and 30%, respectively) but analysis of the distribution of inter-particle intervals among a number of filaments again gave the same fundamental spacing of 40 nm. The error in the measurements (standard deviation approximately +/- 4.2 for 5 nm gold/Fab) is less than earlier estimates for the size of the gold/Fab complex. Measurements on gold/Fab in negative stain suggest that the bound Fab contributes a shell about 2 nm in thickness around the gold particle. The radius of the probe (about 4.5 nm for 5 nm gold/Fab) would then be consistent with the value of error found. The size of the probe suggests that the gold particle binds to the side of the Fab molecule, rather close to the antibody combining site. The potential resolution of the technique may thus be better than originally expected. PMID- 1522141 TI - Patterns of DNA replication in Drosophila polytene nuclei replicating in Xenopus egg and oocyte extracts. AB - We have used Xenopus laevis cell-free extracts to study patterns of DNA replication in polytene nuclei isolated from salivary glands of Drosophila melanogaster 3rd instar larvae. Replication was visualized by supplementation with biotin-dUTP so that nascent DNA became labelled, thus allowing detection with fluorescein or Texas-Red-conjugated streptavidin. Biotin incorporation was dependent on incubation in extracts. Transverse bands were labelled in high-speed supernatants of eggs or oocytes in which replication does not initiate de novo. These patterns corresponded to the patterns of endogenous replication forks in polytene nuclei, monitored by bromodeoxyuridine incorporation in intact salivary glands. By contrast, when nuclei were incubated in low-speed supernatants of eggs, they underwent more extensive chromatin decondensation and initiated replication. The spatial patterns of replication are strikingly different from the endogenous patterns. Instead they closely resemble patterns of clustered replication forks seen in Xenopus sperm nuclei replicating in the extract. This indicates that the egg extract can impose its pattern of replication foci even when the template is presented in the highly organized form of a polytene nucleus. PMID- 1522142 TI - Cytoskeletal and DNA structure abnormalities result from bypass of requirement for the cdc10 start gene in the fission yeast Schizosaccharomyces pombe. AB - The cdc10 gene of the fission yeast S. pombe is required for traverse of the start control in late G1 and commitment to the mitotic cell cycle. To increase our understanding of the events which occur at start, a pseudoreversion analysis was undertaken to identify genes whose products may interact with cdc10 or bypass the requirement for it. A single gene, sct1+ (suppressor of cdc ten), has been identified, mutation of which suppresses all conditional alleles and a null allele of cdc10. Bypass of the requirement for cdc10+ function by sct1-1 mutations leads to pleiotropic defects, including microtubule, microfilament and nuclear structural abnormalities. Our data suggest that sct1 encodes a protein that is dependent upon cdc10+ either for its normal function or expression, or is a component of a checkpoint that monitors execution of p85cdc10 function. PMID- 1522143 TI - Mutants of the microtubule motor protein, nonclaret disjunctional, affect spindle structure and chromosome movement in meiosis and mitosis. AB - The Drosophila microtubule motor protein, nonclaret disjunctional (ncd), is required for proper chromosome distribution in meiosis and mitosis. We have examined the meiotic and mitotic divisions in wild-type Drosophila oocytes and early embryos, and the effects of three ncd mutants (cand, ncd and ncdD) on spindle structure and chromosome movement. The ncd mutants cause abnormalities in spindle structure early in meiosis I, and abnormal chromosome configurations throughout meiosis I and II. Defective divisions continue in early embryos of the motor null mutant, cand, with abnormal early mitotic spindles. The effects of mutants on spindle structure suggest that ncd is required for proper meiotic spindle assembly, and may play a role in forming or maintaining spindle poles in meiosis. The disruption of normal meiotic and mitotic chromosome distribution by ncd mutants can be attributed to its role as a spindle motor, although a role for ncd as a chromosome-associated motor protein is not excluded. The ncd motor protein functions not only in meiosis, but also performs an active role in the early mitotic divisions of the embryo. PMID- 1522144 TI - The upright position of brush border-type microvilli depends on myosin filaments. AB - We have studied the correlation between the actomyosin organization and microvillar position in an epithelial cell line derived from the proximal pig kidney tubule (LLC-PK1). When grown on glass, these cells are approximately 5-6 microns in height and develop numerous microvilli that project from the dorsal membrane. A fairly homogeneous distribution of microvilli was achieved by synchronization of the cell cycle. These microvilli are of the brush border type, as defined by their content of villin and their anchorage in a myosin-rich terminal web-like structure. When LLC-PK1 cells were injected with two monoclonal antibodies against pig brain nonmuscle myosin, in concentrations yielding a 1:1 ratio of antibody to myosin, neither microvillar number nor length was affected. However, when we examined the cells by scanning electron microscopy 1-3 h after microinjection, we found that one of the antibodies (a-PBM 4) had a profound effect on microvillar position: more than 50% were seen tilted or lying prone on the plasma membrane. The microvilli of cells injected with the other antibody (a PBM 9) were not significantly different from those of cells injected with control antibodies. This difference correlates with in vitro properties of the antibodies: a-PBM 4 decreases the actin-activated Mg(2+)-ATPase of pig brain nonmuscle myosin quite substantially, while a-PBM 9 affects it only moderately. These differential effects are probably a consequence of the different epitope location as determined for both antibodies, not of differences in antibody affinity. Our data are compatible with the hypothesis that a-PBM 4 also interferes with the actomyosin interaction in situ, thus decreasing the effective cross-linking of microvillar rootlets by myosin filaments in the terminal web. On the basis of this model, we suggest that myosin filaments are essential for the upright position of brush-border type microvilli. PMID- 1522145 TI - The contribution of the extracellular matrix to gravisensing in characean cells. AB - The cell-extracellular matrix junction, which includes the cell wall and the outer surface of the plasma membrane, may be an essential region for the perception of gravity by the internodal cells of Chara corallina. Typically, when an internodal cell is oriented vertically, the downwardly directed cytoplasmic stream travels at a velocity that is 10% faster than that of the upwardly directed stream. However when the cells are treated with impermeant hydrolytic enzymes that partially digest cellulose or hemicellulose, the cells lose their ability to respond to gravity even though streaming continues. By contrast, enzymes that digest pectins have no effect on the gravity-induced polarity of cytoplasmic streaming. Furthermore, gravisensing is sensitive to protease treatment; Proteinase K, thermolysin and collagenase but not trypsin, alpha chymotrypsin or carboxypeptidase B, inhibit gravisensing. These findings indicate that proteins in the cell-extracellular matrix junction may be required for gravisensing. Moreover, the tetrapeptide Arg-Gly-Asp-Ser (RGDS) inhibits gravisensing in a concentration-dependent manner, indicating that the gravireceptor may be an integrin-like protein. The macromolecules necessary for gravisensing have been localized to the cell ends. As a consequence of the exoplasmic site of action of the enzymes and the tetrapeptides, we interpret the results to mean that they are acting on the gravireceptor, although we cannot eliminate the possibility that they are acting on the signal transduction chain. On the whole, our observations indicate that the cell-extracellular matrix junction is a sine qua non for graviperception in statolith-free Chara internodal cells and we suggest that the gravireceptor is located in this region. PMID- 1522146 TI - The 14 kDa beta-galactoside binding lectin in myoblast and myotube cultures: localization by confocal microscopy. AB - The endogenous 14 kDa beta-galactoside-specific lectin has been localised in myoblasts and myotubes by indirect immunofluorescence using confocal microscopy. The antibodies used in these experiments suggest that in myoblast cultures the lectin is abundant on the cell surface and concentrated at ruffled edges of migrating cells. The quantity and distribution of cell surface lectin is independent of the nature of the substratum and undiminished by brief trypsinisation or lactose-washing of the cell suspension. The lectin is also abundant intracellularly, apparently relatively free in the cytoplasm until the cells approach confluency, when the lectin is concentrated into particular areas of cytoplasm resulting in a 'patchy' appearance of stained cells. After fusion to form multinucleate myotubes, intracellular lectin is less abundant and concentrated at the periphery of myotubes, from where lectin appears to be released in vesicles packed with lectin which 'bud off' from the myotube surface. In recolonising cultures, lectin is apparently more abundant and lectin-packed vesicles can also be seen 'budding off' from myoblasts. In differentiated cultures, extracellular lectin is detected both on the myotube surface and in fibrillar arrays of extracellular material. PMID- 1522147 TI - The interendothelial junction in myocardial capillaries: evidence for the existence of regularly spaced, cleft-spanning structures. AB - Water and hydrophilic solutes cross the endothelium of continuous capillaries via the paracellular cleft and possibly other routes. This pathway shows a selectivity to molecule size and charge. However, it is not yet known which systems confer this selectivity. Isolated rat hearts were perfusion-fixed through the coronary circulation, stained with lanthanum or tannic acid, and further processed for transmission electron microscopy. Thin sections viewed at x 160,000 magnification revealed regularly spaced, cleft-spanning structures in the wider zone of a small percentage of clefts in addition to at least one zonula occludens. Goniometric tilting of the specimen in steps of 5 degrees perpendicular to the plane of the wide zone showed that such "linkers" can be revealed in at least 40% of all clefts. They become visible at some tilt angles, although the same area of the cleft is featureless at other angles. Single linker spacing measurements were obtained using a computerized image analysis system, and compiled in a frequency distribution chart. On the basis of these data, two models of a regular linker distribution within the cleft are illustrated. Our results provide evidence for the presence of regularly spaced, cleft-spanning structures within the interendothelial cleft which may have implications for endothelial cell-cell adhesion and permeability. PMID- 1522148 TI - Redistribution of nuclear lamin A is an early event associated with differentiation of human promyelocytic leukemia HL-60 cells. AB - The nuclear lamina of mammalian somatic cells is characterized by the constitutive presence of lamin B polypeptides while the appearance of lamins A and C generally occur during establishment of a differentiated phenotype. We have used antibodies specific to the unique carboxy-terminal domain of lamin A, i.e. distinct from the shared domains of lamins A and C, to study the individual behaviour of lamin A during establishment of a macrophage phenotype in human HL 60 cells. Lamin A was present as a nuclear cap in the majority of undifferentiated cells and it was redistributed to a full peripheral nuclear location very early after induction of differentiation by phorbol esters, even in the presence of a protein synthesis inhibitor. Induction of the cells into a reversible precommitment state by bromodeoxyuridine was accompanied by a similar redistribution of lamin A that however reverted to a cap after removal of inducer. No changes were observed in the uniform peripheral nuclear location of lamin C under all of these conditions. These results strongly suggest that lamin A plays a role in the early events of cell differentiation. Taken together with previous results on the interaction of A-type lamins with chromatin, these findings offer experimental evidence consistent with the proposed role of A-type lamins, and particularly lamin A, in the process of chromatin reorganization that accompanies the expression of a differentiated phenotype. PMID- 1522149 TI - Protein kinase C isotypes in human erythroleukemia cell proliferation and differentiation. AB - The human erythroleukemia (K562) cell line is induced to differentiate into megakaryocytic cells by treatment with the tumor promoter phorbol myristate acetate (PMA). PMA-induced differentiation is characterized by (1) almost complete cessation of cellular proliferation, (2) expression of the megakaryocytic cell surface marker glycoprotein IIb/IIIa (gpIIIa), (3) increased secretion of granulocyte/macrophage-colony stimulating factor (GM-CSF) and (4) increased secretion of interleukin-6 (IL-6). PMA-induced differentiation is dose dependent with maximal activity seen at 10 nM PMA. In contrast, bryostatin (bryo), a structurally distinct protein kinase C (PKC) activator, fails to induce megakaryocytic differentiation or growth arrest at the concentrations tested (0.01-100 nM). Rather, bryo inhibits PMA-induced growth arrest and megakaryocytic differentiation in a dose-dependent fashion (full inhibition at 100 nM). The divergent biological effects of PMA and bryo correspond to the differential activation and translocation of PKC isotypes in K562 cells. PKC isotype analysis demonstrates that undifferentiated cells express both alpha and beta II PKC but no detectable beta I, gamma or epsilon PKC. Treatment of cells with either PMA or bryo leads to rapid translocation of both alpha and beta II PKC from the cytosol to the non-nuclear particulate fraction. However, bryo also induces selective translocation of beta II PKC to the nuclear membrane.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1522150 TI - Tumour infiltrating macrophages are capable of bone resorption. AB - The cell types responsible for osteolysis associated with skeletal metastasis of solid malignancies are unclear. Tumour infiltrating macrophages (TIMs) isolated from primary mammary carcinomas of C3H/Avy mice were cultured on bone slices to assess their ability to resorb bone. After 14 days in co-culture with murine marrow stromal cell line ST2 and added 1,25-dihydroxyvitamin D3 and dexamethasone, TIMs showed increased tartrate-resistant acid phosphatase activity and formed numerous lacunar resorption pits. In the absence of ST2 cells, TIMs did not form lacunar resorption pits but produced roughening of the bone surface with exposure of mineralized collagen fibres. Normal alveolar macrophages, in both the presence and absence of ST2 cells similarly produced only surface resorption. TIMs are thus capable of both low-grade (surface) and high-grade (lacunar) pathological bone resorption, a specific interaction with stromal cells being necessary for the latter to occur. TIM-mediated bone resorption could account for different clinical and pathological patterns of tumour osteolysis. PMID- 1522151 TI - Interference in vimentin assembly in vitro by synthetic peptides derived from the vimentin head domain. AB - The importance of the amino-terminal domain ("head") of type III intermediate filament (IF) proteins in IF assembly has been examined by testing the influence of synthetic peptides representing a highly conserved decameric motif, KSSSYRRIMFGG, located near the amino terminus of vimentin. When added to soluble vimentin subunits this peptide induces, at fourfold molar excess or slightly above, the appearance of short, regular rod-like structures as determined by electron microscopy of negatively stained and rotary-shadowed preparations as well as by viscometry. At higher peptide concentrations large, irregularly shaped aggregates of mostly non-IF structures formed, but this aggregation was reversible by prolonged dialysis against low ionic strength buffer. The aggregating effect of this peptide was highly sequence-specific and was not seen with point-mutated sequences such as RR----TR or with unrelated peptides containing a central diarginine, indicating that it is not simply ionic. When different hexapeptides representing different "head" positions were compared, only the central sequence, SYRRXF, was as effective as the decamer. The addition of peptide during IF assembly did not prevent filament formation, although 50 fold molar excess of peptide resulted in a drastic increase (up to 40 nm) in the width of the filaments, which also appeared less regular, thus reflecting some interference with assembly. In contrast to the effects on soluble vimentin, the decameric peptide did not disturb IFs, indicating that the binding domain is "masked" or stabilized in the filaments. To identify the domain to which the peptide binds, three different binding assays using vimentin fragments and genetically engineered vimentin deletion mutants were employed. The results indicate that the binding domain of the near-amino-terminal peptide is located at the start of the alpha-helical "rod" domain of the protein. Possible mechanisms of interaction of these two portions of vimentin during IF assembly are discussed. PMID- 1522152 TI - Screening and identification of a gene, PSE-1, that affects protein secretion in Saccharomyces cerevisiae. AB - Utilizing a screening method designed for the identification of genes involved with enhanced protein secretion in Saccharomyces cerevisiae we identified a gene, which we named PSE-1 (Protein Secretion Enhancer). Overexpression of PSE-1 in a multi-copy plasmid, as shown by Northern hybridization, gave a fourfold enhancement in total protein secretion. The repertoire of proteins that are found to be secreted in greater quantities include three known biologically active proteins: k1 killer toxin, alpha-factor, and acid phosphatase. The PSE-1 gene is located on chromosome XII of the yeast genome and codes for a hydrophobic protein containing 1089 amino acids. Haploid yeast cells that contained a LEU2 insertion mutation in PSE-1 grow very poorly, a phenotype similar to other conditional SEC mutants at restrictive temperature. PMID- 1522154 TI - Startling statements. PMID- 1522153 TI - The effects of glucocorticoid therapy. AB - The therapeutic benefit of glucocorticoids appears to derive chiefly from their suppression of immunologic and inflammatory responses, but beyond these generalized phenomena, there are a number of tissue-specific effects. Increasing knowledge of these actions is shedding light on such issues as steroid resistance and steroid-induced adrenocortical insufficiency. PMID- 1522155 TI - The equivalence of antithrombolytic agents. PMID- 1522156 TI - Current status of HIV therapy: II. Opportunistic diseases. AB - Infections and malignancies account for most deaths in patients with AIDS and will continue to do so as long as HIV-induced immunosuppression is progressive and irreversible. Co-trimoxazole has emerged as the preferred agent for prevention of Pneumocystis carinii pneumonia. As appropriate broad-spectrum agents are developed, multiple opportunistic pathogen prophylaxis could become effective. PMID- 1522157 TI - Laughing on the outside, crying on the inside. PMID- 1522158 TI - Parasites and the germ theory of disease. PMID- 1522159 TI - Cri du chat and Potter syndromes: a decision to abort. PMID- 1522160 TI - A perplexing case of diurnal edema in a young woman. PMID- 1522161 TI - Chronic fatigue syndrome. PMID- 1522162 TI - Effective management of penetrating head injury. AB - Although head injuries are usually easily recognized, other, less obvious lesions should also be promptly investigated. In either case, outcome is often determined in the first few minutes and hours of management. PMID- 1522163 TI - Arks and genetic bottlenecks. PMID- 1522164 TI - Other faces of AIDS. PMID- 1522165 TI - Multidrug-resistant nosocomial TB: newest facet of the HIV epidemic. PMID- 1522166 TI - Elderly patients afraid to eat. PMID- 1522167 TI - Leptospirosis in aseptic meningitis. PMID- 1522169 TI - A strategy for the solitary thyroid nodule. PMID- 1522168 TI - Therapeutic approaches to recurrent peptic ulcer disease. PMID- 1522170 TI - Stories of epilepsy: 1880-1930. PMID- 1522171 TI - Treatment choices in chronic myelogenous leukemia. PMID- 1522172 TI - Determination of sulphonamides in pork meat extracts by capillary zone electrophoresis. AB - For sixteen sulphonamides the effective mobility was measured as a function of pH and from the effective mobilities determined in two different electrolyte systems the pK value and mobility at infinite dilution were calculated. A pH of 7.0 was found to be the optimum pH for the separation for both standard mixtures and mixtures of sulphonamides dissolved in pork meat extracts. For the determination of the sulphonamides in pork meat only a very simple pretreatment consisting of extraction with acetonitrile and centrifugation is suitable, as the matrix effects at pH 7.0 do not affect the separation. Calibration graphs for five sulphonamides were constructed, and regression coefficients of at least 0.999 were obtained. The limit of detection for the method varies from 2 to 9 ppm for a pressure injection time of 10 s (injection volume ca. 18 nl) using a Polymicro Technology capillary of length 116.45 cm, distance between injection and detection 109.75 cm and I.D. 50 microns. PMID- 1522173 TI - Apparent inter-channel interference in dual-electrode electrochemical detection. AB - During the course of routine high-performance liquid chromatographic analyses of brain catecholamines using dual-electrode electrochemical detection, we encountered an unusual negative peak in the lower-voltage channel. Subsequent investigations suggested that this peak was caused by tyrosine which produced a positive peak in the higher-voltage channel. Our investigations indicate that compounds that generate a peak in one channel appear to be responsible for complex peaks in a second channel set at a lower voltage, close to or below that necessary for oxidation. The complex peaks are biphasic; a sharp negative peak coinciding with the positive peak on the higher-voltage channel, followed by a positive peak. This effect was not specific for tyrosine, but was observed on the lower-voltage channel with all compounds tested that produced signals on the high voltage channel. The cause of the problem is unknown, but it appears to be an artifact of the electrical coupling of the two electrode channels in a dual channel system. PMID- 1522174 TI - Counter-current chromatography of lipoproteins with a polymer phase system using the cross-axis synchronous coil planet centrifuge. AB - Lipoproteins were separated by counter-current chromatography using the type-XLL coil planet centrifuge. The separation was performed with a polymer phase system composed of 16% (w/w) polyethylene glycol 1000 and 12.5% (w/w) dibasic potassium phosphate by eluting the lower phase at a flow-rate of 0.5 ml/min. About 5 ml of the sample solution containing approximately 150 mg of a lipoprotein mixture were loaded. High- and low-density lipoproteins were resolved within 12 h. Each component was detected by gel electrophoresis with oil red staining. PMID- 1522175 TI - Direct high-performance liquid chromatographic separation of enantiomeric peptidoleukotriene antagonists. AB - Enantiomeric peptidoleukotriene antagonists, SK&F R-106203 and SK&F S-106203 can be effectively separated on a cellulose tris(3,5-dimethylphenylcarbamate) chiral stationary phase. The utility of this chiral high-performance liquid chromatographic method in assigning absolute stereochemistry to SK&F S-106203-Z2, a non-crystalline amorphous compound which is not amenable to single crystal X ray analysis, is demonstrated by correlation with the absolute configuration determined crystallographically for a second salt form. PMID- 1522176 TI - DNA electrophoresis in uncross-linked polyacrylamide solution, studied by epifluorescence microscopy. AB - Electrophoresis of human DNA fragments (approximately 1 x 10(5) to 1 x 10(7) bases in size) was conducted in a solution of uncross-linked polyacrylamide contained in a horizontally mounted 1 mm diameter glass tube and monitored by epifluorescence microscopy. In presence of the polymer, molecular conformations described as a "trailing network" of DNA and a globular "head" were observed. The migration velocity varies between species differing in the size of the "head", and in the ratio between the size of the "head" and that of the trailing "network". By contrast, in pure buffer, lambda phage DNA migrates in a globular form at a mobility consistent with known macroscopic data. When electrophoresis in the polymer solution of an agarose plug preparation of Schizosaccharomyces pombe DNA was carried out after melting at 70 degrees C, a migrating DNA-agarose complex was observed. The complex was not fully dissociated by an agarose hydrolyzing enzyme (Gelase). PMID- 1522177 TI - Ion- and ligand-exchange chromatography of proteins using porous zirconium oxide supports in organic and inorganic Lewis base eluents. AB - The applicability of an eluotropic scale pertaining to the desorption of low molecular weight Lewis base solutes from zirconium oxide is examined for its ability to rationalize the retention of proteins on this substrate. The strongest Lewis base eluents (phosphate and fluoride) are able to bring about elution of nearly all proteins provided that their initial mobile phase concentration almost saturates the eluent's adsorption isotherm. In contrast, weaker Lewis bases such as borate, sulfate and bromide are able to elute only those proteins which are retained primarily by ionic interactions. In weak eluents, proteins that contain a large number of accessible Lewis base sites are not eluted from the support. The effect of ionic strength and a variety of Lewis base eluents were also examined. PMID- 1522178 TI - Simultaneous purification of the neuroproteins synapsin I and synaptophysin. AB - A procedure for the simultaneous purification of synapsin I and synaptophysin from calf brain was developed. Demyelinated membranes were extracted with 2% Triton X-100 and 2 M KCl. The extracted proteins were separated by weak cation exchange chromatography on carboxymethyl-Sepharose Fast Flow. Synaptophysin was finally purified by preparative sodium dodecyl sulphate-polyacrylamine gel electrophoresis and synapsin I by affinity chromatography using a calmodulin Sepharose column. The recovery obtained was 40 micrograms/g in brain for synaptophysin and 25 micrograms/g in brain for synapsin I. PMID- 1522179 TI - Determination of nitroxynil in cow milk by reversed-phase high-performance liquid chromatography with dual-electrode coulometric detection. AB - A sensitive and specific method is described for the determination of nitroxynil (fasciolicide) residues in cow milk. The milk samples were extracted with acetone and acetonitrile, following clean-up using a simple liquid-liquid extraction step. Nitroxynil was separated from the matrix peaks by reversed-phase high performance liquid chromatography and detected using dual-electrode coulometric detection. The mobile phase was a mixture (20:80, v/v) of acetonitrile and 0.05 M potassium dihydrogenphosphate with the pH adjusted to 4.0. The flow-rate was 1 ml/min at 40 degrees C. The applied potentials of detectors 1 and 2 were maintained at -0.7 and +0.2 V, respectively. Average recoveries (n = 5) of nitroxynil from milk samples spiked at concentrations of 0.01 and 0.1 micrograms/ml were found to be 92.0% and 97.0% with coefficients of variation of 6.2% and 2.2%, respectively. The detection limit of nitroxynil in milk was 0.7 ng/ml. During the analysis of 30 raw cow milk and 140 market milk samples, nitroxynil was detected at a level of 4 ng/ml in one raw cow milk sample. PMID- 1522180 TI - Reversed-phase high-performance liquid chromatography of several metal-8 quinolinethiol complexes. AB - The reversed-phase high-performance liquid chromatography of 8-quinolinethiol (Hqt) complexes of Fe, Co, Ni, Cu, Zn, Hg and Pb on an octadecyl-bonded silica gel stationary phase was examined. The Pb complex dissociated in the column. The retention and separation of other complexes depended on the composition of the mobile phase. EDTA as an additive displaced the Zn complex and eliminated its peak. All the other metal complexes and also Hqt and its disulphide were separated in 23 min by using methanol-water (82:18, v/v) as the mobile phase. The complexes formed by the reaction of Co(II) and Hqt gave three peaks, which were assigned as fac(S)-CoIII(qt)3, mer(S)-CoIII(qt)3 and CoII(qt)2, respectively. This method is applicable to the simultaneous determination of Fe, Co, Ni, Cu and Hg. PMID- 1522181 TI - Structure-retention index relationships for derivatized monosaccharides on non polar gas chromatography columns. AB - A gas chromatographic method for predicting the retention index of a derivatized monosaccharide is presented. The procedures are especially useful to detect and predict minute quantities of sugars in biological or chemical samples. Monosaccharides are first converted to the alditols and then derivatized by acetylation, permethylation or silylation. The derivatized monosaccharide structure-retention index relationship that has been developed is useful in the identification of unknown monosaccharides that can be readily confirmed by gas chromatography-mass spectrometry. PMID- 1522182 TI - Micellar electrokinetic chromatographic study of hydroquinone and some of its ethers. Determination of hydroquinone in skin-toning cream. AB - The separation of hydroquinone and some of its ether derivatives was studied by micellar electrokinetic chromatography with sodium dodecyl sulphate as an anionic surfactant in the background electrolyte. The optimized method was used for the determination of hydroquinone in a sample of skin-toning cream. On-column detection at 254 nm with caffeine as an internal standard gave good quantitative results. PMID- 1522183 TI - Embryological observations on the female genital tract. AB - The embryology of the genital tract and urinary system is described, and the hypothesis is advanced that the vagina is an organ embryologically derived from the mesonephric or Wolffian ducts in addition to the Mullerian tubercle. This is based on experimental studies and case reports in the literature and our own cases of genital malformations, especially in patients with unilateral renal agenesis and an ipsilateral blind vagina. The importance of the mesonephric ducts as guides or 'inductor' elements for adequate Mullerian development is emphasized. A new embryological classification of female genital malformations is proposed, based on these embryological concepts. PMID- 1522184 TI - A stereological study of the human ovarian surface epithelium. AB - The surface of the ovary has been found to be composed of two types of epithelial cells called A and B cells which are found in their own respective zones, the A and B zones. A quantitative study was undertaken to determine the mean cell volumes and cell ultrastructure. Ovarian biopsies were taken from six women and A and B zones, having been identified by scanning electron microscopy, were re embedded for transmission electron microscopy. Stereological measurements using point sampled intercepts were made on vertical sections and showed that B cells are significantly larger than A cells. The volume weighted mean cell volumes of the A and B cells were 237.3 microns 3 and 676.8 microns 3 respectively. The volume fractions of the nucleus and mitochondria were similar in the two cell types. Although the vesicle content of each type was similar, a large variation between cases made the interpretation difficult. The stereological tools used in this study proved to be easy and efficient estimators of surface cell ultrastructure and give an important direction for ultrastructural research. PMID- 1522185 TI - Implications of ultrasonically diagnosed polycystic ovaries. I. Correlations with basal hormonal profiles. AB - The incidence of ultrasonically diagnosed polycystic ovaries (PCO) was studied in 389 Arab patients with different types of menstrual dysfunction and 100 normal women with regular menstruation. Two-hundred-and-forty-six patients (63.2%) were found to have PCO but only 206 (53.0%) were confirmed as cases of polycystic ovarian disease (PCOD) on endocrine grounds. Polycystic ovaries were diagnosed in 50% of patients with hyperprolactinaemia, 36.4% with hypothyroidism, 23.7% with hypothalamic dysfunction, 100% with adrenal 21-hydroxylase deficiency and in 16.0% of normal women. More women with PCOD presented with oligomenorrhoea or dysfunctional uterine bleeding (77.7%) and hirsutism (72.3%) but obesity had no discriminating value between the groups with different diagnoses. Ultrasonic diagnosis of PCO should be supplemented with an endocrine biochemical assessment to prevent overdiagnosis of PCOD and to exclude other endocrine dysfunctions. PMID- 1522186 TI - The correlation of interleukin 1 and tumour necrosis factor to oestradiol, progesterone and testosterone levels in periovulatory follicular fluid of in vitro fertilization patients. AB - Data has accumulated suggesting reciprocity between cytokines and the reproductive system. The present study was performed in order to evaluate the correlation between interleukin 1 (IL-1) and tumour necrosis factor (TNF) concentrations in follicular fluid and its oestradiol, progesterone and testosterone levels. A total of 39 follicular fluid samples, from eight patients undergoing in-vitro fertilization and embryo transfer were evaluated. All of the patients were treated by a midluteal (long) protocol involving a gonadotrophin releasing hormone agonist (GnRHa) coupled with follicular phase human menopausal gonadotrophin. Mean levels in follicular fluid of IL-1, TNF, oestradiol, progesterone and testosterone were 1.58 +/- 0.42 fmol/0.1 ml, 4.69 +/- 4.18 pg/ml, 28.5 +/- 58.1 ng/ml, 2360.5 +/- 2846.3 ng/ml and 7.22 +/- 7.08 ng/ml respectively. There was a significant (P less than 0.01) positive correlation between IL-1 and progesterone levels. There was no significant correlation between the different lymphokines and oestradiol secretion, oocyte fertilization, embryo quality and pregnancy rates. It is concluded that IL-1 and TNF exist in follicular fluid. It may be hypothesized that IL-1 has a local regulatory action, possibly promoting luteinization. PMID- 1522187 TI - Positive feedback effect of oestradiol in superovulated women. AB - To investigate the mechanism of blockage of the luteinizing hormone (LH) surge in superovulated women, six normally ovulating women were studied in three cycles: a spontaneous cycle treated with exogenous oestrogen (oestradiol benzoate cycle), a cycle treated with follicle stimulating hormone (FSH; 225 IU/day; FSH cycle) and a cycle treated with FSH plus exogenous oestrogen (FSH + oestradiol benzoate cycle). Oestradiol benzoate was injected i.m. on cycle days 4 (0800 and 2000 h), 5 (0800 h) and 6 (0800 h) at doses of 0.5, 1.0, 2.0 and 2.5 mg respectively to achieve supraphysiological levels of serum oestradiol. Exogenous oestrogen (supraphysiological oestradiol levels) induced an LH surge in all six women in the oestradiol benzoate cycles, but failed to stimulate an LH surge in three of the six patients during treatment with FSH. In three patients treated with FSH, an LH surge was stimulated both by supraphysiological (FSH + oestradiol benzoate cycles) and 'high normal' oestradiol levels (FSH cycles), while in three patients treated with FSH only, the LH surge was blocked, although the threshold level for the positive feedback effect had been exceeded by cycle day 9. We conclude that in women, supraphysiological concentrations of oestradiol exert a positive feedback effect on LH secretion. It is suggested that the occurrence of an LH surge in cycles superovulated with FSH is not dependent on serum oestradiol concentrations, but mainly on the strength of ovarian inhibitory substances. PMID- 1522188 TI - The effect of follicle maturing drugs on side of ovulation in successive cycles. AB - Our previous study has demonstrated that ovulation in unstimulated cycles is random with an equal likelihood of ipsilateral or contralateral ovulation occurring in the following cycle. This study evaluated women taking ovulation inducing drugs to see if the side of ovulation in the preceding cycle has an influence on the side of ovulation in the succeeding cycle. Ovulatory patterns in consecutive pairs of cycles in anovulatory women treated with ovulation-inducing drugs were evaluated through sonographic studies of follicular maturation. The results demonstrated that when unilateral ovulation occurred, there was an equal likelihood of ipsilateral or contralateral ovulation in the succeeding cycle. However, ovulation-inducing drugs increase the incidence of bilateral or multiple ovulation. PMID- 1522189 TI - Prerequisite work-up of the couple before in-vitro fertilization. AB - Prerequisite examinations, including immune status for rubella and hepatitis B antigens, cultures for Chlamydia trachomatis and mycoplasmas, Pap smear and hystersalpingogram were performed in 227 couples before their enrollment into an in-vitro fertilization (IVF) programme. The examinations were completed in 187 couples. Immune status for rubella had already been documented in 45% of the women: of the remainder, 11 patients were not immune (6%). A screening test for hepatitis B antigens had already been documented in only 10% of the patients; eight of the remaining women (5%) were carriers of hepatitis B antigen. C. trachomatis and Mycoplasma hominis were each isolated from 14% of the patients and Ureaplasma urealiticum from 16%. Pap smears had been previously performed in only 35% of the enrolled women. Six (5%) of the 122 newly referred cases had cervical intra-epithelial dysplasia. In 21 (11%) cases some pathology in the uterine cavity was demonstrated. One patient conceived after diagnostic hysteroscopy; another two patients conceived following lysis of adhesions and before IVF treatment. The results of this study show the importance of the preparatory examinations before the IVF and embryo transfer procedure, and raise the medical and medico-legal aspects of this prerequisite work-up. PMID- 1522191 TI - A prospective controlled study of in-vitro fertilization, gamete intra-fallopian transfer and intrauterine insemination combined with superovulation. AB - The relative effectiveness of in-vitro fertilization (IVF), gamete intra Fallopian transfer (GIFT) and intrauterine insemination (IUI) combined with superovulation in the treatment of infertility were compared in 151 couples undergoing a single cycle of treatment. Treatment was selected as appropriate (IVF for tubal disease, GIFT or IUI/superovulation for nontubal infertility) but possible bias due to non-randomization was overcome by all couples having had favourable fertilization in a previous cycle of IVF. Furthermore, in a preliminary study of initial IVF treatment in 265 couples from whom the study patients were drawn, implantation and pregnancy rates in the diagnostic groups were similar. In the definitive study comparing IVF, GIFT and IUI/superovulation, the pregnancy rate observed with GIFT was highest (40%) but this was not significantly higher than with IVF (28%) or IUI/superovulation (20%). However, the implantation rate per egg transferred by GIFT (21%) was significantly higher than the implantation rate per embryo transferred by IVF (11%). Although the pregnancy rates with GIFT were not statistically greater than with IVF, a significant advantage is likely to be observed in larger groups in view of the better implantation rate. The lower pregnancy rates with IUI superovulation are to be expected because of limited ovarian stimulation, they are nevertheless of comparative interest. PMID- 1522190 TI - Luteal phase support in in-vitro fertilization using gonadotrophin releasing hormone analogue before ovarian stimulation: a prospective randomized study of human chorionic gonadotrophin versus intramuscular progesterone. AB - This study was conducted to compare the endocrine milieu and pregnancy rates in an in-vitro fertilization and embryo transfer (IVF-ET) programme employing a gonadotrophin-releasing hormone agonist (GnRHa) and human menopausal gonadotrophin (HMG) when either human chorionic gonadotrophin (HCG) or progesterone were used for luteal phase support. A total of 121 IVF-ET treatment cycles were prospectively studied. All patients started leuprolide acetate in the midluteal phase and it was continued for at least 10 days. When oestradiol levels were less than 150 pmol/l, HMG was started. When at least three follicles were greater than or equal to 17 mm in diameter, HCG 5000 IU i.m. was given. Oocytes were retrieved using transvaginal ultrasound and embryos were transferred 48 h later. The patients' cycles were prospectively randomized to receive HCG (72 cycles) or progesterone (49 cycles) luteal support. The HCG group received 1500 IU i.m. on days 3, 6 and 9 after the initial trigger. The progesterone group received 12.5 mg i.m. q.d. starting from the day after the HCG trigger. The dose of progesterone was increased to 25 mg i.m. q.d. starting on the day of embryo transfer and continued for 17-21 days. If the patient became pregnant, this dose of progesterone was continued until fetal heart activity was visualized by ultrasound. Mean ages, number of eggs retrieved, embryos transferred, oestradiol levels on the day of the HCG trigger, oestradiol and progesterone at the time of embryo transfer were the same in both groups.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1522192 TI - Different phenotypes in two cases of an apparently identical familial (Yq;13p) translocation. AB - A chromosome 13 with extra material on the short arm was observed in a 17-year old boy showing defects in skeletal growth, an altered hormone profile and asthenoteratozoospermia, and in a 46 XX fetus subjected to prenatal diagnosis. The abnormal chromosome 13 had been transmitted from phenotypically normal parents who were the mother (case 1) and the father (case 2). The extra material on the abnormal chromosome 13 was brightly fluorescent after Q-banding, and positive in C-banding (CBG) and distamycin A-Dapi (DA-Dapi) banding. Staining of the nucleolus organizer region indicated its retention. In-situ hybridization of a Yq-specific repetitive DNA probe to chromosomal spreads from both cases demonstrated that the der(13) chromosome contains sequences of the Yq heterochromatic region. However, the apparently identical unbalanced (Y;13) translocation may either interfere (case 1) or not (father of case 2) with meiotic or postmeiotic sperm cell development. PMID- 1522193 TI - Purification and localization of a calcium-binding protein in human spermatozoa. AB - The purpose of this study was to purify a calcium-binding protein (CalBP) from human spermatozoa of 226 men and to determine the localization of this protein in spermatozoa. The sperm cells were extracted with 0.6 M KCl, and the KCl extract was then subjected to gel filtration and high performance liquid chromatography. Two CalBPs of Mr = 38 kDa and 52 kDa were found by 45Ca(2+)-binding on blotted proteins. Only a 52 kDa CalBP (CalBP-52) was purified to a final yield of 0.007%. The isoelectric point of this protein was 5.1. The human CalBP-52 reacted with rabbit antiserum directed against rat 52 kDa CalBP. An immunocytochemical study showed that this protein was localized on the sperm head. It is postulated that this protein may have important functions related to Ca(2+)-transport into sperm cells. PMID- 1522194 TI - Recovery of artificially inseminated spermatozoa from the fallopian tubes of a woman undergoing total abdominal hysterectomy. AB - Investigation of the process of sperm transport within the human female reproductive tract must involve the recovery of spermatozoa from the oviducts of women post-coitum or insemination. This case report describes the insemination of a 40-year-old woman with her partner's semen and the subsequent recovery of spermatozoa from her Fallopian tubes, removed at hysterectomy, 2 days post ovulation. The number of spermatozoa present within the tubes and their location was ascertained using a flushing technique and scanning electron microscopy (SEM). The total number of spermatozoa present within the flushed tube was calculated to be 142, whilst the total number of spermatozoa calculated to be present within the scanned tube was 673. The proportional distribution of spermatozoa within the tubes was virtually identical by the two techniques used. The largest population of spermatozoa resided within the ampulla (66.1% SEM, 68.3% flush), and the smallest population resided within the intramural region (14.9% SEM, 13.4% flush). PMID- 1522195 TI - Quantitative ultrastructural analysis of sperm tails reveals flagellar defects associated with persistent asthenozoospermia. AB - Sperm tail morphology was examined in 10 infertile asthenozoospermic men to determine whether poor sperm motility was caused by ultrastructural defects of the flagellum. In this quantitative analysis, the numbers of outer doublet and central pair microtubules, outer and inner dynein arms and radial spokes were counted in transverse sections of 75 axonemes from each patient and compared with similar data previously collected from 10 men with normal semen characteristics. Four patients had axonemal defects: two had severe microtubule abnormalities and two had more subtle but statistically significant deficiencies of dynein arms. These abnormalities would not have been detected by more commonly used qualitative examination. Three patients had no detectable ultrastructural abnormalities of the sperm tail, possibly indicating a metabolic deficiency. A further three patients had mid-piece abnormalities. Two had few, if any, flagellar mitochondria and the third patient had irregular and disorganized mitochondria. Quantitative ultrastructural analysis has revealed axonemal abnormalities in seven of 10 patients with previously unexplained asthenozoospermia. PMID- 1522196 TI - The removal of morphologically abnormal sperm forms by phagocytes: a positive role for seminal leukocytes? AB - A preliminary investigation was undertaken further to determine the function of the leukocytic cells found in semen. We performed semen analysis and quantified leukocyte subsets using immunocytochemical staining techniques in ejaculates of 351 patients. Leukocyte profiles were examined in relation to sperm morphological data for evidence of a sperm removal/selection process. Three types of seminal phagocytic cell were found to contain spermatozoa: small polymorphonuclear leukocytes (approximately 10-12 microns), monocytes of similar size and much larger (30-40 microns) macrophages capable of engulfing multiple sperm heads. The total leukocyte count (P less than 0.01), the numbers of phagocytic cells i.e. polymorphonuclear leukocytes (P less than 0.05), monocyte/macrophages (P less than 0.01) and HLA-DR positive cells (P less than 0.01), were significantly higher in those samples with greater than 50% ideal sperm forms. Significantly fewer of these same cell types were observed in samples with greater than 50% head defects. There was no difference in the number of tail or midpiece defects between leukocytospermic (greater than 10(6)/ml) and non-leukocytospermic semen samples. Oligozoospermic samples contained significantly fewer leukocytes (P less than 0.005), although above a concentration of 5 x 10(6)/ml, the sperm number was not correlated with leukocyte number. These data, along with repeated observation of spermatozoa or sperm fragments within phagocytic cells, support the hypothesis that leukocytes have a role in the removal of abnormal spermatozoa from the ejaculate. PMID- 1522197 TI - Origin, development and ultrastructure of boar spermatozoa with folded tails and with two tails. AB - Spermatozoa from the three epididymal regions (head, body and tail) of healthy and sexually mature boars have been examined by light microscopy, and scanning and transmission electron microscopy. The origin, development and external and internal morphologies of aberrant spermatozoa with folded tails and spermatozoa with one or two heads and two fused tails have been established. A count carried out in each region of the epididymis indicated that significant differences (P less than 0.01) exist in the frequencies of each type of malformation and the epididymal region from which the spermatozoa come. Spermatozoa with folded tails at Jensen's ring originate in the cauda of the epididymis from immature spermatozoa that have not ejected the distal cytoplasmic droplet. The plasma membrane which covers the main piece is fused with the membranes of the midpiece, the connecting piece and the head. The fibrous sheath deforms the mitochondrial sheath and is placed between the plasma membrane and the postacrosomal dense lamina. Spermatozoa with one head and two fused tails originate in the epididymal body from spermatozoa with one head and two unfused tails coming from the cephalic region of the epididymis. Spermatozoa with two heads and two fused tails originate in the cephalic region of the epididymis by head-to-head agglutination of two spermatozoa and later fusion of their tails. The frequency of spermatozoa with two fused tails increases as they progress through the epididymal duct. Their tails, parallel in monocephalic spermatozoa and helicoid in bicephalic spermatozoa, have two complete axonemal axes. In their midpiece, the mitochondrial sheaths of the two axes are fused, producing an 8-shaped sheath. PMID- 1522198 TI - Cruciate thinning of the zona pellucida for more successful enhancement of blastocyst hatching in the mouse. AB - Implantation rates remain low following human in-vitro fertilization (IVF). Suboptimal culture conditions may limit the ability of embryos to hatch as blastocysts, and artificial opening of the zona pellucida has been proposed as a means to promote subsequent hatching (assisted hatching). Such techniques must have minimal adverse effects on the embryos, while maximizing the potential for an embryo to hatch fully as a blastocyst. In a mouse model, we compared embryonic development after zona drilling, and cruciate thinning of the zona (CTOZ) intended to simulate the natural thinning of the zona pellucida. Using acidic Tyrode's solution both zona drilling and cruciate-thinning were performed on day 3 morulae. On day 4 the rates of complete hatching of blastocysts were 0/165, 24/172 and 72/175 in control, zona drilled and thinned groups respectively (P less than 0.0001). On day 5 the rates of complete hatching in the same groups were 20/165, 54/172 and 120/175 respectively (P less than 0.00001) and by day 6, 66/165, 74/172 and 130/175 respectively (P less than 0.00001). The rate of arrest at the morula stage was 24/172 versus 8/175 in the zona drilled and thinned groups respectively (P less than 0.005, whilst the rate of arrest at the blastocyst stage was 21/172 versus 14/175 respectively (NS). Hence cruciate thinning of the zona appears less detrimental at the morula stage than zona drilling, but eventual rates of arrest at the blastocyst stage were comparable. Both techniques significantly increased the rate of hatching, but zona drilling did not guarantee complete hatching.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1522199 TI - Usefulness of partial dissection of the zona pellucida in a human in-vitro fertilization programme. AB - The influence of partial zona dissection (PZD) on the fertilization rate was studied in 34 couples with a history of fertilization failure and/or severe sperm deficiency. Overall, PZD improved the rate of monospermic fertilization compared to controls (41/254 versus 6/111: P less than 0.001) and fertilization was achieved in 50% of cases. However, the results differed according to the seminal characteristics. In 10 couples with at least two in-vitro fertilization (IVF) trials entailing total fertilization failure and with semen defined as normal, PZD did not significantly improve the monospermic fertilization rate (6/44 in the PZD group versus 2/39 among controls). A benefit related to PZD was evident in 33 attempts with severe sperm deficiency. In this group, only four of 72 unmanipulated control oocytes were fertilized but the monospermic fertilization rate was 14.6% for PZD oocytes. The rates of polyspermy were 40% and 14.6% in the groups with normal and abnormal semen parameters respectively. Of 33 trials with defective spermatozoa, 20 reached the stage of embryo transfer and three pregnancies were obtained, of which one aborted at 9 weeks. PMID- 1522200 TI - Secretion of alpha-immunoreactive inhibin by human pre-embryos cultured in vitro. AB - alpha-Immunoreactive inhibin was measured using an enzyme immunoassay kit in the culture medium (Ham's F-10 medium supplemented with 14% heat-inactivated human serum) from day 3 or 4 to day 14 post-fertilization of 31 surplus pre-embryos from eight women participating in an in-vitro fertilization programme. Inhibition secretion was demonstrated in all of them from the fourth day after fertilization (mean +/- SEM: 3.0 +/- 0.7 U) and was independent of the morphological development of pre-embryos (2-4 cells, n = 4; 6-8 cells, n = 4; 8-10 cells, n = 9; 10-12 cells, n = 4; morulae, n = 5 and blastocysts, n = 4). On days 7, 10, 13 and 14 post-fertilization, mean inhibin values +/- SEM for non-disintegrated pre embryos were respectively: 6.5 +/- 0.9 U, 12.3 +/- 2.0 U, 16.8 +/- 3.2 U and 20.2 +/- 3.7 U; however, when disintegration was noted on days 10 and 13 after fertilization, inhibin mean values were 9.0 +/- 1.4 U and 8.4 +/- 1.7 U respectively. Inhibin levels were significantly correlated with human chorionic gonadotrophin levels in the same culture media only on day 13, while correlation with pregnancy specific beta 1-glycoprotein occurred on day 7 post-fertilization. In conclusion, early human pre-embryos secrete alpha-immunoreactive inhibin before the cytotrophoblast is formed. This secretion increases significantly with time when development is continued, while disintegration is followed by a net decline in the rate of inhibin release. PMID- 1522201 TI - Inositol stimulates DNA and protein synthesis, and expansion by rabbit blastocysts in vitro. AB - The effect of different concentrations (0, 0.6, 3, 15, 75 and 375 microM) of myo inositol on the development of rabbit morulae to expanded blastocysts was investigated in terms of blastocyst expansion and synthesis of DNA and protein, as measured by incorporation of [3H]thymidine and [14C]amino acids into acid precipitable material. A concentration of 15 microM inositol caused a 2.8-fold increase in blastocyst expansion (P less than 0.01), a 9.9-fold increase in thymidine incorporation into DNA (P less than 0.01) and a 3.6-fold increase in amino acid incorporation into protein (P less than 0.01). There were no significant differences in the range from 15 to 375 microM inositol. PMID- 1522202 TI - In-vitro co-culture of early stage caprine embryos with oviduct and uterine epithelial cells. AB - Early stage caprine embryos were incubated with goat oviduct and uterine cells to evaluate whether these cells could be used as a somatic cell culture system to enhance development through the developmental block at the 8- to 16-cell stage during in-vitro culture. Following gonadotrophin treatment and natural mating, 2- to 4-cell embryos were surgically recovered from donor females for in-vitro culture studies. In Experiment 1, embryos were equally and randomly allotted to culture treatments of either culture medium plus caprine oviduct cells or culture medium alone. In both treatment groups, embryos were incubated in Medium-199 with 10% fetal bovine serum, 0.25% lactalbumin and 1% antibiotic-antimycotic at 37 degrees C in a humidified atmosphere of 5% CO2 in air. In Experiment 2, similar embryos were cultured in the same medium with either caprine oviduct cells, caprine uterine cells or sequentially incubated with oviduct cells and then uterine cells during a corresponding incubation interval. The culture conditions in Experiment 2 were the same as in Experiment 1. Following 72 h in culture, (Experiment 1), significantly more embryos developed through the in-vitro developmental block into blastocysts and hatched blastocysts when cultured with oviduct cells compared with no embryos developing through the in-vitro block when incubated with medium alone. In Experiment 2, caprine embryos co-cultured with oviduct cells alone resulted in more embryos developing into blastocysts and hatched blastocysts compared with those co-cultured with uterine cells alone.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1522203 TI - Effect of incubation volume and embryo density on the development and viability of mouse embryos in vitro. AB - The morphology, cleavage rate and viability of preimplantation embryos from random bred Swiss mice were assessed after culture in different incubation volumes and embryo densities. Decreasing the incubation volume, from 320 to 20 microliters, significantly increased blastocyst cell number (P less than 0.01) and embryo development after transfer (P less than 0.01). Increasing the number of embryos incubated per drop from 1 to 16 significantly increased the number of two-cell embryos reaching the blastocyst stage in 5 or 320 microliters. Culturing embryos in groups significantly increased blastocyst cell numbers in all volumes employed and elevated embryo viability. Such observations are consistent with the hypothesis that the preimplantation mammalian embryo produces a factor(s) which can stimulate its own development. The results of this study have implications for clinical in-vitro fertilization, where embryos are routinely cultured individually in relatively large volumes. PMID- 1522204 TI - The expression and localization of mRNA for colony-stimulating factor (CSF)-1 in human term placenta. AB - A 4-kb mRNA for colony-stimulating factor 1 (CSF-1) was detected in normal human placenta at term by Northern blot analysis. In-situ hybridization revealed that the mRNA for CSF-1 was localized in the mesenchymal cells of the chorionic villous stroma, but not in the trophoblasts or capillary epithelial cells. Because there are significant numbers of tissue macrophages (Hofbauer cells) in the placental stroma and because the receptor for CSF-1 (the c-fms proto-oncogene product) is known to be expressed by trophoblasts, our results suggest that CSF-1 produced by placental stromal cells may act as a growth and survival factor for human placental macrophages and trophoblasts. PMID- 1522205 TI - Hydatidiform mole with coexisting twin pregnancy after gamete intra-fallopian transfer. AB - The pregnancy of a 31-year-old infertility patient is described. After gamete intra-Fallopian transfer, her pregnancy evolved uneventfully until the 18th week of gestation, when vaginal bleeding occurred. Ultrasonographic findings suggested a molar pregnancy with two live fetuses. At 24 weeks gestation, two male infants were spontaneously delivered. Fetal (46 XY) and molar (46 XX) karyotypes and post mortem findings were consistent with a bizygotic twin pregnancy associated with a complete hydatidiform mole. The pathogenesis and obstetrical management are discussed. PMID- 1522206 TI - The personality and motivation of semen donors: a comparison with oocyte donors. AB - Seventeen consecutively recruited candidates for semen donation were evaluated by a psychologist with testing and a structured interview. Most men (71%) were motivated by financial compensation. Only 29% would donate semen if records were open to potential offspring. Fifty-nine per cent of the men were rated as excellent candidates from a psychological perspective and 35% were rated as acceptable with slight reservations. One was excluded as a donor. Psychological testing revealed mildly abnormal subscale scores for 35% of donors. Forty-seven per cent had histories of minor depressive or anxiety episodes and 35% had had periods of heavy alcohol use. Compared to oocyte donors at the same institution, the men were less altruistic, more affluent, and more likely to have abused alcohol. Women had more traumatic family and reproductive histories. Psychological evaluation can be a valuable tool in gamete donor selection. PMID- 1522207 TI - Clinical trials in assisted reproduction. PMID- 1522208 TI - Cytogenetic analysis of human oocytes form fertile women. PMID- 1522209 TI - Regulation of catalase in Neisseria gonorrhoeae. Effects of oxidant stress and exposure to human neutrophils. AB - We studied the effects of oxidant stress on the catalase activity and hydrogen peroxide sensitivity of Neisseria gonorrhoeae. N. gonorrhoeae is an obligate pathogen of man that evokes a remarkable but ineffective neutrophil response. Gonococci make no superoxide dismutase but express high catalase activity. Gonococcal catalase activity increased threefold when organisms were subjected to 1.0 mM hydrogen peroxide. This increase in catalase activity was marked by a parallel increase in protein concentration recognized by a rabbit polyclonal antibody raised against the purified gonococcal enzyme. Catalase was primarily localized to the gonococcal cytoplasm in the presence or absence of stress; only a single isoenzyme of catalase could be identified. Exposure of gonococci to neutrophil-derived oxidants was accomplished by stimulating neutrophils with phorbol myristate acetate or by using gonococcal Opa variants that interacted with neutrophils with different degrees of efficiency. Gonococci exposed to neutrophils demonstrated a twofold increase in catalase activity in spite of some reduction in viability. Exposure of gonococci to 1.0 mM hydrogen peroxide made the organisms significantly more resistant to higher concentrations of hydrogen peroxide and to neutrophils than control organisms. These results suggest that catalase is an important defense for N. gonorrhoeae during attack by human neutrophils. The rapid response of this enzyme to hydrogen peroxide should be taken into consideration in studies designed to evaluate the interaction between neutrophils and gonococci. PMID- 1522210 TI - Organ distribution of the three rat endothelin messenger RNAs and the effects of ischemia on renal gene expression. AB - To determine the organ distribution of production of the three endothelin (ET) isopeptides, we have developed three ribonuclease protection assays specific for the messenger RNAs (mRNAs) of rat ETs 1, 2, and 3.12 organs from adult Sprague Dawley rats were examined: heart, lung, liver, spleen, kidney, stomach, small intestine, large intestine, testis, muscle, salivary gland, and brain. The mRNA for ET1 was five times more abundant in the lung than in any other organ studied, moderate expression was seen in the large intestine, and lower levels of mRNA were detected in each of the other organs examined. ET2 was expressed at high level in both large and small intestine and at low level in stomach, muscle, and heart, but ET2 mRNA could not be detected elsewhere. ET3 mRNA was found in all organs, particularly in small intestine, lung, kidney, and large intestine. Because of reports suggesting that ETs might be involved in the hypoperfusion and hypofiltration observed in postischemic kidneys, we have also studied levels of mRNA in kidneys that had previously been subjected to 25 or 45 min of clamping of the renal pedicle. At 6 h after 45 min of ischemia, ET1 mRNA increased to a peak of 421 +/- 69% (mean +/- SEM, n = 3) of that in a standard renal RNA preparation. By contrast, ET3 mRNA decreased in the postischemic organ, falling to a value of 19 +/- 2% of standard at the same time point. The effects of ischemia on ET1 and ET3 mRNAs were long-lasting, with elevation of ET1 and depression of ET3 persisting for days. ET2 mRNA remained undetectable throughout. These findings (a) support a role for ET1 in postischemic renal vascular phenomena and (b) demonstrate a situation in which the expression of ET isoforms is clearly subject to differential regulation. PMID- 1522211 TI - Antibodies to T- and L-isoforms of the cytoskeletal protein, fimbrin, in patients with systemic lupus erythematosus. AB - The cytoskeleton is a complex network of proteins that maintain cell shape, mobility, and organelle function. Its components can be divided into three distinct classes: microfilaments, microtubules, and intermediate filaments. Fimbrins are microfilament proteins, a family of cytoplasmic phosphoproteins. Expression of the L-fimbrin isoform is restricted to replicating blood cells and expression of the T-fimbrin isoform to replicating cells of solid tissues. Sera from normals and from patients with systemic lupus erythematosus (SLE), juvenile arthritis, rheumatoid arthritis, Sjogren's syndrome, osteoarthritis, vasculitis, scleroderma, and mixed connective tissue disease were tested for the presence of antibodies to T- and L-fimbrin by ELISA, using purified recombinant fimbrin. The mean OD of sera from SLE patients was significantly higher than in normals (T fimbrin, P less than 0.0001; L-fimbrin, P less than 0.001). 48 of 98 SLE sera had antibodies to T-fimbrin; 32 had antibodies to L-fimbrin; 20 had antibodies to both; 28 had only anti-T, and 12 had only anti-L-fimbrin. The mean OD for sera of the other rheumatic diseases was not significantly different from normals. The presence of either L- or T-fimbrin antibody was associated with pleuropericarditis (P = 0.015), photosensitivity (P = 0.011), and anti-Sm antibody (P = 0.010). Central nervous system SLE was associated with the presence of the L-fimbrin antibody alone (P = 0.016). There was a strong association between DR7 (but not other MHC alleles) and anti-L-fimbrin antibodies in SLE patients (chi square = 18; P less than 0.00002). No MHC association was observed with anti-T-fimbrin antibodies. PMID- 1522213 TI - Mucopolysaccharidosis type IVA. N-acetylgalactosamine-6-sulfate sulfatase exonic point mutations in classical Morquio and mild cases. AB - Mucopolysaccharidosis type IVA (MPS IVA) results from a genetic deficiency of N acetylgalactosamine-6-sulfate (Gal-NAc6S) sulfatase. We have identified two different exonic mutations causing GalNAc6S sulfatase deficiency in two unrelated Japanese families, in one patient with classical Morquio disease, and in two brothers with a mild form of MPS IVA. The nucleotide sequence of the full-length cDNA derived from a patient with classical Morquio disease revealed a two-base deletion at nucleotide position 1343-1344 (1344-1345 or 1345-1346) that altered the reading frame (designated 1342delCA). This mutation, inherited from the proband's consanguineous parents, was revealed by TaqI restriction analysis of a cDNA fragment amplified by the polymerase chain reaction. In the proband with the mild form of the disease, a C to G transversion at nucleotide 667 predicted the substitution of Lys for Asn204 (N204K). Since a new AluI site was created by the N204K mutation, restriction analysis indicated that the affected brothers were homozygous for this mutation, as confirmed by the finding that both their parents had this lesion. Transient expression in GalNAc6S sulfatase deficient fibroblasts of these two mutant alleles showed completely deficient or markedly decreased enzyme activities, thereby indicating that these two mutations were responsible for the enzyme deficiency. PMID- 1522212 TI - Messenger RNA expression and synthesis of endothelin-1 along rat nephron segments. AB - The kidney both produces and responds to endothelin. We examined the production and the expression of mRNA of endothelin-1 (ET-1) in tubule suspensions and microdissected nephron segments. ET-1 production was measured by RIA using an ET 1-specific antibody. We applied the reverse transcription and polymerase chain reaction (PCR) technique to detect ET-1 mRNA along the nephron segments. Stimulation of ET-1 production was observed in the presence of FCS and transforming growth factor-beta (TGF-beta) in inner medullary tubules but not in cortical or outer medullary tubule suspensions. Among dissected nephron segments, ET-1 production was observed in glomeruli and inner medullary collecting ducts (IMCD), whereas it was negligible in proximal convoluted tubules (PCT) and medullary thick ascending limbs (MAL). In addition, the PCR product of ET-1 mRNA was also higher in glomeruli and IMCD, whereas it was undetectable in PCT and MAL. Furthermore, FCS and TGF-beta increased ET-1 mRNA in microdissected glomeruli and IMCD. These data clearly demonstrated that the production sites of ET-1 are glomeruli and IMCD among the nephron segments. ET-1 is an autocrine factor in these sites. PMID- 1522214 TI - Purification and partial sequencing of the nuclear autoantigen RA33 shows that it is indistinguishable from the A2 protein of the heterogeneous nuclear ribonucleoprotein complex. AB - RA33 is a nuclear autoantigen with an apparent molecular mass of 33 kD. Autoantibodies against RA33 are found in about 30% of sera from RA patients, but only occasionally in sera from patients with other connective tissue diseases. To characterize RA33, the antigen was purified from HeLa cell nuclear extracts to more than 90% homogeneity by affinity chromatography on heparin-Sepharose and by chromatofocusing. Sequence analysis of five tryptic peptides revealed that their sequences matched corresponding sequences of the A2 protein of the heterogeneous nuclear ribonucleoprotein (hnRNP) complex. Furthermore, RA33 was shown to be present in the 40S hnRNP complex and to behave indistinguishably from A2 in binding to single stranded DNA. In summary, these data strongly indicate that RA33 and A2 are the same protein, and thus identify on a molecular level a new autoantigen. PMID- 1522215 TI - Enhanced membrane binding of autoantibodies to cultured keratinocytes of systemic lupus erythematosus patients after ultraviolet B/ultraviolet A irradiation. AB - Although sunlight is known to induce skin lesions in patients with systemic lupus erythematosus (SLE) and to exacerbate systemic manifestations, the underlying mechanisms remain obscure. We report experiments that show enhanced binding of IgG autoantibodies to the cell surface membrane of ultraviolet-B (UVB) irradiated (200-1,600 J/m2) cultured SLE keratinocytes in 10 out of 12 such cell strains. The autoantibody probes showing increased binding were directed against the soluble intracellular antigens, Sm, RNP, SSA/Ro, SSB/La, whereas serum with anti dsDNA activity did not demonstrate such binding. Control keratinocytes from several sources shared low level binding of autoantibodies after ultraviolet light exposure. In addition, 4/6 UVB-sensitive SLE strains showed increased autoantibody binding to the surface of SLE keratinocytes after UVA exposure (50 150 kJ/m2), but of lower magnitude. When UVB-sensitive nonirradiated SLE strains were exposed to autologous serum, 3/8 sera demonstrated a striking increase in IgG binding, which increased further after UVB exposure. Enhanced expression of saline-soluble intracellular antigens on the cell surface membrane of patient, but not control, keratinocytes may, in part, explain the photosensitivity of patients with SLE. PMID- 1522216 TI - Cellular immune reactivity to recombinant OspA and flagellin from Borrelia burgdorferi in patients with Lyme borreliosis. Complexity of humoral and cellular immune responses. AB - Patients with Lyme borreliosis (LB) usually develop a vigorous T cell response against the causative pathogen Borrelia burgdorferi, but little is known about the antigens recognized in the cellular response. Therefore, T cell reactivities against whole bacteria, recombinant 31-kD (outer surface protein A, [OspA]), and 41-kD proteins (flagellin) from B. burgdorferi were studied in patients with LB, non-LB patients, and healthy donors. In parallel, specific antibodies were determined by Western blot analysis. Virtually all patients with LB exhibited marked cellular responses to whole B. burgdorferi, which were significantly elevated compared with the control groups in both early and late disease stages. However, analyses using the purified antigens OspA and flagellin revealed considerable heterogeneity in the cellular reactivities among individuals as well as variations during the course of infection. T cell responses to OspA were significantly increased in patients with early LB compared with both control groups whereas in late-stage disease responses only exceeded those of non-LB patients and were not different from normal donors. Cellular immune reactivities to flagellin were significantly higher only in early LB compared with both control groups. Reciprocally, several control subjects demonstrated marked cellular responses to OspA and flagellin, suggesting that reactions to these proteins may not always be related to LB. T cell reactivity did not correlate well with the presence of specific antibodies. Almost all seropositive patients in both early and late stage LB had serum antibodies against flagellin, but antibodies to OspA were detectable only in a subset of late LB sera. These data demonstrate the complexity of the humoral and the cellular immune responses to components of B. burgdorferi. PMID- 1522217 TI - Phagocytosis of unopsonized Pseudomonas aeruginosa by murine macrophages is a two step process requiring glucose. AB - Pseudomonas aeruginosa is an important pulmonary pathogen in cystic fibrosis, but the means by which it evades host defenses is understood poorly. Macrophages (M phi) are critical in protecting the lung and mucosal surfaces against infection and may need to perform their functions in the absence of opsonins before the evolution of an inflammatory response. The purpose of the present study was to define factors that regulate the capacity of macrophages to mediate nonopsonic phagocytosis. Phagocytosis of unopsonized P. aeruginosa by murine peritoneal and pulmonary alveolar M phi s was absolutely dependent upon the presence of glucose; only D-mannose could substitute. Glucose-dependent phagocytosis appears to be selective for P. aeruginosa by M phi s; ingestion of unopsonized zymosan, opsonized P. aeruginosa, EIgG, and E (IgM)C occurred in the presence or absence of glucose as did-ingestion of unopsonized P. aeruginosa by polymorphonuclear leukocytes. M phi binding and phagocytosis of unopsonized P. aeruginosa appeared to occur by a mechanism independent of complement receptor 3 and mannose receptors. Phagocytosis of P. aeruginosa killed by tobramycin or Formalin was glucose dependent, suggesting that the glucose exerted its effects on the M phi rather than the bacteria. The predilection of P. aeruginosa for lower airway disease in patients with cystic fibrosis might be explained in part by the unique dependency upon glucose for M phi phagocytosis. PMID- 1522218 TI - Lupus anticoagulant activity of autoimmune antiphospholipid antibodies is dependent upon beta 2-glycoprotein I. AB - It has been reported that antiphospholipid autoantibodies do not recognize phospholipid alone, but rather the plasma protein beta 2-glycoprotein I (beta 2GPI), or a beta 2GPI-phospholipid complex. In vitro beta 2GPI binds to anionic phospholipids and inhibits the prothrombinase activity of procoagulant membranes. In light of the fact that lupus anticoagulants, a type of antiphospholipid antibody, have similar anticoagulant properties, the relationship of beta 2GPI to lupus anticoagulant activity was investigated. IgG from patients with autoimmune diseases or syphilis were tested for anticardiolipin reactivity and lupus anticoagulant activity in the presence and absence of beta 2GPI. As expected, anti-cardiolipin reactivity associated with autoimmune disease was beta 2GPI dependent. In contrast, IgG from a patient with syphilis recognized cardiolipin alone and binding was inhibited by beta 2GPI. Autoimmune antiphospholipid antibodies prolonged the dilute Russell viper venom time of normal plasma, but had no effect on beta 2GPI-depleted plasma. Antiphospholipid antibodies associated with syphilis had no anticoagulant effect. RP-1, an anti-beta 2GPI mAb, had anticoagulant effects similar to those of autoimmune antiphospholipid antibodies. These data demonstrate that antiphospholipid autoantibodies exert lupus anticoagulant activity via an interaction with beta 2GPI. These antibodies and RP-1 appear to amplify the anticoagulant effect of beta 2GPI itself. PMID- 1522219 TI - Induction of antiphospholipid autoantibodies by immunization with beta 2 glycoprotein I (apolipoprotein H). AB - A subset of patients with systemic lupus erythematosus has autoantibodies to acidic phospholipids. Since lipids are poor immunogens, the mechanism responsible for the induction of these antibodies is unclear. Immunization of a normal rabbit and normal mice with purified human beta 2-glycoprotein I (apolipoprotein H) resulted in the production of high levels of two non-cross-reactive antibody populations, anti-apolipoprotein H, and antiphospholipid. The antiphospholipid antibodies had binding specificities indistinguishable from autoantibodies obtained from human and murine lupus. These findings suggest a novel mechanism for the induction of antiphospholipid autoantibodies. PMID- 1522220 TI - Advanced glycosylation endproducts block the antiproliferative effect of nitric oxide. Role in the vascular and renal complications of diabetes mellitus. AB - Advanced glycosylation endproducts (AGEs) accumulate on long-lived tissue proteins such as basement membrane collagen and have been implicated in many of the long-term complications of diabetes mellitus. These products originate from glucose-derived Schiff base and Amadori products but undergo a series of complex rearrangement reactions to form ultimately protein-bound, fluorescent heterocycles. AGEs can react with and chemically inactivate nitric oxide (NO), a potent endothelial cell-derived vasodilator and antiproliferative factor. Since mesenchymal cell proliferation is an early and characteristic lesion of diabetic vasculopathy and glomerulopathy, we investigated the possibility that collagen bound AGEs functionally inactivate the antiproliferative effect of NO. In model cell culture systems, AGEs were found to block the cytostatic effect of NO on aortic smooth muscle and renal mesangial cells. The inactivation of endothelial cell-derived NO by basement membrane AGEs may represent a common pathway in the development of the accelerated vascular and renal disease that accompany long term diabetes mellitus. PMID- 1522221 TI - Human bactericidal/permeability-increasing protein and a recombinant NH2-terminal fragment cause killing of serum-resistant gram-negative bacteria in whole blood and inhibit tumor necrosis factor release induced by the bacteria. AB - The bactericidal/permeability-increasing protein (BPI) of neutrophils and BPI fragments neutralize the effects of isolated Gram-negative bacterial lipopolysaccharides both in vitro and in vivo. Since endotoxin most commonly enters the host as constituents of invading Gram-negative bacteria, we raised the question: Can BPI and its bioactive fragments also protect against whole bacteria? To determine whether the bactericidal and endotoxin-neutralizing activities of BPI/fragments are expressed when Gram-negative bacteria are introduced to the complex environment of whole blood we examined the effects of added BPI and proteolytically prepared and recombinant NH2-terminal fragments on: (a) the fate of serum-resistant encapsulated Escherichia coli, Klebsiella pneumoniae, and Pseudomonas aeruginosa that survive the antibacterial actions of whole blood and (b) the ability of these bacteria to trigger cytokine release. Added BPI in nanomolar concentrations killed each of three encapsulated strains of E. coli and in closely parallel fashion inhibited tumor necrosis factor (TNF) release. Holo-BPI and its NH2-terminal fragment were equipotent toward a rough LPS chemotype K1-encapsulated strain, but the fragment was substantially more potent than holo-BPI toward two encapsulated smooth LPS chemotype strains. TNF release induced by K. pneumoniae and P. aeruginosa was also inhibited by both holo-BPI and fragment but, at the protein concentrations tested, P. aeruginosa was killed only by the fragment and K. pneumoniae was not killed by either protein. The bactericidal action of BPI/fragment toward E. coli is inhibited by C7-depleted serum, but accelerated by normal serum, indicating that BPI, acting in synergy with late complement components, enhances extracellular killing of serum-resistant bacteria. Thus, BPI and an even more potent NH2-terminal fragment may protect against Gram-negative bacteria in the host by blocking bacterial proliferation as well as endotoxin-mediated effects, not only as components of the intracellular antibacterial arsenal of the neutrophil, but also as potentially therapeutic extracellular agents. PMID- 1522222 TI - Endothelial production of C-type natriuretic peptide and its marked augmentation by transforming growth factor-beta. Possible existence of "vascular natriuretic peptide system". AB - C-type natriuretic peptide (CNP), the third member of the natriuretic peptide family, is thus far known to be distributed mainly in the central nervous system and is considered to act as a neuropeptide, in contrast to atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP), which act as cardiac hormones. Recently, we and others have demonstrated that the ANP-B receptor, which is selectively activated by CNP, is localized not only in the central nervous system but in peripheral tissues, including blood vessels. This finding has made us speculate regarding the peripheral production of CNP. In the present study, cultured endothelial cells were examined for CNP production by RIA and Northern blot analysis. CNP-like immunoreactivity was detected in the conditioned media of endothelial cells. Northern blot analysis detected CNPmRNA with a size of 1.2 kb. In addition, transforming growth factor (TGF)-beta, one of the key growth factors for vascular remodeling, markedly stimulated the expression of CNPmRNA and induced a tremendous increase in CNP secretion. We could also detect CNP transcript in the bovine thoracic aorta using the reverse transcription polymerase chain reaction method. The present study demonstrates the endothelial production of CNP and suggests that a member of the natriuretic peptide family may act as a local regulator in vascular walls. Since evidence for the pathophysiological importance of the vascular renin-angiotensin system has been accumulating and the natriuretic peptide system is known to be antagonistic to the renin-angiotensin system, the possible existence of "vascular natriuretic peptide system" may prove to be of physiological and clinical relevance. PMID- 1522223 TI - Filamentous, helical, and tubular microstructures during cholesterol crystallization from bile. Evidence that cholesterol does not nucleate classic monohydrate plates. AB - Precipitation of cholesterol in gallbladder bile is believed to produce platelike cholesterol monohydrate crystals directly. We report complementary time-lapse microscopic studies of cholesterol crystallization from model bile that reveal initial assembly of filamentous cholesterol crystals covered by a monomolecular layer of lecithin. Over a few days, the filaments evolved through needle, helical, and tubular microstructures to form classical platelike cholesterol monohydrate crystals. Similar crystallization phenomena were observed in human gallbladder biles from cholesterol but not pigment stone patients. Synchrotron x ray diffraction of the earliest filaments suggested a cholesterol monohydrate polymorph or admixture with an anhydrous cholesterol precursor. However, density gradient centrifugation of filamentous crystals revealed that their density was 1.032 g/ml, consistent with anhydrous cholesterol. Conventional x-ray diffraction of transitional crystalline forms was consistent with pure cholesterol monohydrate crystals, as were the equilibrium platelike crystals. These novel findings suggest that crystalline cholesterol in bile may not be completely mature or hydrated initially, but undergoes a series of transformations to become thermodynamically stable monohydrate plates. These observations have important implications for understanding the control of cholesterol crystallization in bile, as well as explaining putative crystal cytotoxicity during gallstone formation. PMID- 1522224 TI - Hypertrophic gastropathy resembling Menetrier's disease in transgenic mice overexpressing transforming growth factor alpha in the stomach. AB - Transforming growth factor alpha (TGF alpha) is thought to participate in the normal and pathologic processes of numerous tissues, including the gastric mucosa. To explore its role in vivo, transgenic mice were generated overexpressing TGF alpha in the stomach. TGF alpha induced dramatic structural and functional lesions of the glandular stomach that were similar to Menetrier's disease in humans. Transgenic mice developed severe adenomatous hyperplasia that resulted in a striking nodular thickening or hypertrophy of the gastric mucosa. Secretions obtained from affected stomachs contained no detectable gastric acid, suggesting that parietal cell function had been greatly impaired. These findings demonstrate that overproduction of TGF alpha can stimulate cellular proliferation, suppress acid secretion, and perturb organogenesis of the stomach of transgenic mice. Moreover, TGF alpha may contribute to the pathogenesis of related human hypertrophic gastropathies, such as Menetrier's disease. PMID- 1522225 TI - Antiatherogenic effects of L-arginine in the hypercholesterolemic rabbit. AB - The purpose of this study was to determine if chronic administration of L arginine, the precursor of endothelium-derived relaxing factor (EDRF), normalizes endothelium-dependent relaxation and decreases atherosclerosis in hypercholesterolemic animals. Male rabbits were fed (a) normal rabbit chow; (b) 1% cholesterol diet; or (c) 1% cholesterol diet supplemented by 2.25% L-arginine HCl in drinking water. Arginine supplementation doubled plasma arginine levels without affecting serum cholesterol values. After 10 wk, the thoracic aorta was harvested for studies of vascular reactivity and histomorphometry. Endothelium dependent relaxations (to acetylcholine and calcium ionophore A23187) were significantly impaired in thoracic aortae from animals fed a 1% cholesterol diet. By contrast, vessels from hypercholesterolemic animals receiving L-arginine supplementation exhibited significantly improved endothelium-dependent relaxations. Responses to norepinephrine or nitroglycerin were not affected by either dietary intervention. Histomorphometric analysis revealed a reduction in lesion surface area and intimal thickness in thoracic aortae from arginine supplemented animals compared to those from untreated hypercholesterolemic rabbits. This is the first study to demonstrate that supplementation of dietary L arginine, the EDRF precursor, improves endothelium-dependent vasorelaxation. More importantly, we have shown that this improvement in EDRF activity is associated with a reduction in atherogenesis. PMID- 1522226 TI - The tissue distribution of tumor necrosis factor biosynthesis during endotoxemia. AB - Tumor necrosis factor (TNF) is a protein hormone implicated in the development of septic shock and other pathologic states. However, complexities inherent in detecting TNF synthesis by individual tissues have left the precise origins of this protein undefined. In addition, the possibility that localized TNF production may contribute to the pathogenesis of organ-specific diseases such as type I diabetes has not been explored in vivo. We have developed a transgenic mouse line bearing a reporter gene construct in which the TNF coding sequence and introns are replaced by a chloramphenicol acetyltransferase (CAT) coding sequence. In normal transgenic animals, CAT activity is expressed only in the thymus. When endotoxin is administered to the animals, CAT activity is also evident in kidney, heart, islets of Langerhans, spleen, lung, fallopian tubes, and uterus, but not in other organs. The biosynthesis of CAT in vivo correlated with tissue capacity to secrete TNF in vitro. Thus, TNF was secreted by all the tissues that expressed CAT, including lung, spleen, thymus, uterus/fallopian tubes, pancreatic islets, renal glomeruli, and cultured cardiac cells after exposure to endotoxin. PMID- 1522227 TI - Airway cooling and rewarming. The second reaction sequence in exercise-induced asthma. AB - To determine if a relationship exists among the magnitude and rate of airway rewarming, and the severity of bronchial obstruction in thermally induced asthma, we had seven subjects perform three- to four-point stimulus response curves with isocapnic hyperventilation of frigid air with and without pretreatment with inhaled norepinephrine. The latter was employed to alter the heat supplied to the airway walls by producing vasoconstriction. 1-s forced expiratory volume (FEV1) was measured before and 5 min after the cessation of each bout of hyperpnea and before and after norepinephrine. On a separate day, the subjects repeated the above challenges while the temperatures of the airstream in the intrathoracic airways were measured. Prenorepinephrine, FEV1 progressively decreased in a stimulus response fashion as ventilation rose, while norepinephrine shifted this curve to the right. As the level of ventilation increased, the size of the temperature difference between the cooling of hyperpnea and the rewarming of recovery followed suit, and their magnitude was linearly related to the severity of bronchial narrowing. Reducing the mucosal blood supply of the airways with norepinephrine limited rewarming and attenuated the obstructive response. These data demonstrate that the airway narrowing that develops following hyperpnea and the magnitude of the thermal differences are related, and that alterations in blood supply directly affect bronchial heat flux and influence obstruction. PMID- 1522228 TI - Intracellular ATP can regulate afferent arteriolar tone via ATP-sensitive K+ channels in the rabbit. AB - Studies were performed to assess whether ATP-sensitive K+ (KATP) channels on rabbit preglomerular vessels can influence afferent arteriolar (AA) tone. K+ channels with a slope conductance of 258 +/- 13 (n = 7) pS and pronounced voltage dependence were demonstrated in excised patches from vascular smooth muscle cells of microdissected preglomerular segments. Channel activity was markedly reduced by 1 mM ATP and in a dose-dependent fashion by glibenclamide (10(-9) M to 10(-6) M), a specific antagonist of KATP channels. 10(-5) M diazoxide, a K+ channel opener, activated these channels in the presence of ATP, and this effect was also blocked by glibenclamide. To determine the role of these KATP channels in the control of vascular tone, diazoxide was tested on isolated perfused AA. After preconstriction from a control diameter of 13.1 +/- 1.1 to 3.5 +/- 2.1 microns with phenylephrine (PE), addition of 10(-5) M diazoxide dilated vessels to 11.2 +/- 0.7 microns, which was not different from control. Further addition of 10(-5) M glibenclamide reconstricted the vessels to 5.8 +/- 1.5 microns (n = 5; P less than 0.03). In support of its specificity for KATP channels, glibenclamide did not reverse verapamil induced dilation in a separate series of experiments. To determine whether intracellular ATP levels can effect AA tone, studies were conducted to test the effect of the glycolytic inhibitor 2-deoxy-D-glucose. After preconstriction from 13.4 +/- 3.2 to 7.7 +/- 1.3 microns with PE, bath glucose was replaced with 6 mM 2-deoxy-D-glucose. Within 10 min, the arteriole dilated to a mean value of 11.8 +/- 1.4 microns (n = 6; NS compared to control). Subsequent addition of 10(-5) M glibenclamide significantly reconstricted the vessels to a diameter of 8.6 +/- 0.5 micron (P less than 0.04). These data demonstrate that KATP channels are present on the preglomerular vasculature and that changes in intracellular ATP can directly influence afferent arteriolar tone via these channels. PMID- 1522229 TI - Prevention of diabetes in nonobese diabetic mice by dendritic cell transfer. AB - The purpose of this study was to determine the effect of dendritic cell (DC) transfers on the incidence of diabetes in female nonobese diabetic (NOD) mice. Groups of 4-wk-old NOD female mice were given a single foot pad of DCs (70-90% purity) isolated from the draining lymph nodes (LN) of the pancreas (PLN), the cervical LNs, or the axillary/inguinal LNs. In addition, other groups of NOD mice received purified spleen DCs, purified PLN T cells (the major contaminating population in DC preparations), or the injection vehicle PBS. All groups were monitored for diabetes for one year. Significant protection from diabetes was observed in NOD mice receiving greater than 1 x 10(4) PLN DCs in comparison to mice receiving other DCs populations, PLN T cells, or PBS (P less than 0.05). The pancreata of NOD mice that received PLN DCs demonstrated significantly lower levels of lymphocytic infiltration in the islets that age-sex matched nondiabetic female NOD control mice (P less than 0.05). LN cells from nondiabetic NOD mice that received PLN DC protected irradiated female recipients from the adoptive transfer of diabetes to a greater degree than LN cells from age and sex matched nondiabetic female NOD mice that did not receive PLN DC transfers at 36 d (P = 0.014) and at 1 yr (P = 0.0015) after transfer. These data suggest that the PLN DC transfers are able to modulate autoimmunity and limit diabetes expression in the NOD mouse. PLN DCs transfers may regulate autoimmunity by the induction of regulatory cells. PMID- 1522230 TI - On the mechanism of parathyroid hormone stimulation of calcium uptake by mouse distal convoluted tubule cells. AB - PTH stimulates transcellular Ca2+ absorption in renal distal convoluted tubules. The effect of PTH on membrane voltage, the ionic basis of the change in voltage, and the relations between voltage and calcium entry were determined on immortalized mouse distal convoluted tubule cells. PTH (10(-8) M) significantly increased 45Ca2+ uptake from basal levels of 2.81 +/- 0.16 to 3.88 +/- 0.19 nmol min-1 mg protein-1. PTH-induced 45Ca2+ uptake was abolished by the dihydropyridine antagonist, nifedipine (10(-5) M). PTH did not affect 22Na+ uptake. Intracellular calcium activity ([Ca2+]i) was measured in cells loaded with fura-2. Control [Ca2+]i averaged 112 +/- 21 nM. PTH increased [Ca2+]i over the range of 10(-11) to 10(-7) M. Maximal stimulation to 326 +/- 31 nM was achieved at 10(-8) M PTH. Resting membrane voltage measured with the potential sensitive dye DiO6(3) averaged -71 +/- 2 mV. PTH hyperpolarized cells by 19 +/- 4 mV. The chloride-channel blocker NPPB prevented PTH-induced hyperpolarization. PTH decreased and NPPB increased intracellular chloride, measured with the fluorescent dye SPQ. Chloride permeability was estimated by measuring the rate of 125I- efflux. PTH increased 125I- efflux and this effect was blocked by NPPB. Clamping voltage with K+/valinomycin; depolarizing membrane voltage by reducing extracellular chloride; or addition of NPPB prevented PTH-induced calcium uptake. In conclusion, PTH increases chloride conductance in distal convoluted tubule cells leading to decreased intracellular chloride activity, membrane hyperpolarization, and increased calcium entry through dihydropyridine-sensitive calcium channels. PMID- 1522231 TI - Angiotensin II receptor blockade limits glomerular injury in rats with reduced renal mass. AB - The effects of angiotensin II (AII) blockade were compared with the effects of angiotensin converting enzyme inhibition in rats with reduced nephron number. Rats were subjected to five-sixths renal ablation and divided into four groups with similar values for blood pressure and serum creatinine after 2 wk. Group 1 then served as untreated controls, while group 2 received the AII receptor antagonist MK954 (which has previously been designated DuP753), group 3 received the converting enzyme inhibitor enalapril, and group 4 received a combination of reserpine, hydralazine, and hydrochlorothiazide. Micropuncture and morphologic studies were performed 10 wk later. Converting enzyme inhibition, AII receptor blockade, and the combination regimen were equally effective in reversing systemic hypertension (time-averaged systolic blood pressure: group 1, 185 +/- 5 mmHg; group 2, 125 +/- 2 mmHg; group 3, 127 +/- 2 mmHg; group 4, 117 +/- 4 mmHg). Micropuncture studies showed that glomerular transcapillary pressure was reduced significantly by converting enzyme inhibition and by AII blockade but not by the combination regimen (delta P: group 1, 49 +/- 1 mmHg; group 2, 42 +/- 1 mmHg; group 3, 40 +/- 2 mmHg, group 4, 47 +/- 1 mmHg). Reduction of systemic blood pressure was associated with the development of markedly less proteinuria and segmental glomerular sclerosis in rats receiving enalapril and MK954 but not in rats receiving the combination regimen (prevalence of glomerular sclerotic lesions: group 1, 41 +/- 4%; group 2, 9 +/- 1%; group 3, 9 +/- 1%; group 4, 33 +/ 6%). These results indicate that the effects of converting enzyme inhibition on remnant glomerular function and structure depend on reduction in AII activity and are not attributable simply to normalization of systemic blood pressure. PMID- 1522232 TI - Enhanced production of monocyte chemoattractant protein-1 in rheumatoid arthritis. AB - Cells within the synovial tissue may recruit mononuclear phagocytes into the synovial fluid and tissues of arthritic patients. We investigated the production of the chemotactic cytokine monocyte chemoattractant protein-1 (MCP-1) using sera, synovial fluid, synovial tissue, as well as macrophages and fibroblasts isolated from synovial tissues from 80 arthritic patients. MCP-1 levels were significantly higher (P less than 0.05) in synovial fluid from RA patients (mean 25.5 +/- 8.1 ng/ml [SE]) compared to synovial fluid from osteoarthritis (OA) patients (0.92 +/- 0.08), or from patients with other arthritides (2.9 +/- 1.5). MCP-1 levels in RA sera (8.44 +/- 2.33) were significantly greater than MCP-1 in normal sera (0.16 +/- 0.06). The quantities of RA synovial fluid IL-8, which is chemotactic for neutrophils and lymphocytes, and MCP-1 were strongly positively correlated (P less than 0.05). To examine the cellular source of MCP-1, RA synovial tissue macrophages and fibroblasts were isolated. Synovial tissue fibroblasts did not express MCP-1 mRNA, but could be induced to produce MCP-1 by stimulation with either IL-1 beta, tumor necrosis factor-alpha (TNF-alpha), or LPS. In contrast, unlike normal peripheral blood monocytes or alveolar macrophages, RA synovial tissue macrophages constitutively expressed MCP-1 mRNA and antigen. Immunohistochemical analysis of synovial tissue showed that a significantly greater percentage of RA macrophages (50 +/- 8%) as compared to either OA macrophages (5 +/- 2) or normal macrophages (1 +/- 0.3) reacted with anti-MCP-1 antibodies. In addition, the synovial lining layer reacted with MCP-1 in both RA and OA synovial tissues. In contrast, only a minority of synovial fibroblasts (18 +/- 8%) from RA synovium were positive for immunolocalization of MCP-1. These results suggest that synovial production of MCP-1 may play an important role in the recruitment of mononuclear phagocytes during inflammation associated with RA and that synovial tissue macrophages are the dominant source of this cytokine. PMID- 1522233 TI - Lower sedentary metabolic rate in women compared with men. AB - Since females have a greater prevalence of obesity compared with males, the question arises whether females have lower metabolic rate than males after adjusting for differences in body weight and composition. 24-h energy expenditure (24EE), basal metabolic rate (BMR), and sleeping metabolic rate (SMR) were measured in a respiratory chamber in 235 healthy, nondiabetic Caucasian subjects (114 males, 121 females). Body composition was determined by hydrodensitometry. 24EE was 124 +/- 38 kcal/d (P less than 0.002) higher in males than females after adjusting for differences in fat-free mass, fat mass, and age. Spontaneous physical activity was not significantly different between males and females. Since adjusted 24EE was 106 +/- 39 kcal/d (P less than 0.01) higher in females during the luteal phase of the menstrual cycle compared with females during the follicular phase, energy expenditure was analyzed in a subset (greater than 50 yr) to minimize the confounding effect of menstrual status. 24EE (160 +/- 66 kcal/d; P less than 0.03), BMR (116 +/- 45; P less than 0.02), and SMR (208 +/- 68 kcal/d; P less than 0.005) were higher in males compared with females of the older subset after adjusting for differences in body composition, age, and activity. In summary, sedentary 24EE is approximately 5-10% lower in females compared with males after adjusting for differences in body composition, age, and activity. PMID- 1522234 TI - Anoxia-hyperoxia induces monocyte-derived interleukin-8. AB - Ischemia-reperfusion and hyperoxia-induced pulmonary injury are associated with the presence of activated neutrophils (PMN) and cellular injury. Although the signals orchestrating the directed migration of these PMN during the pathogenesis of these disease states remain to be fully elucidated, it appears they may be dependent upon the production of certain neutrophil activating/chemotactic factors such as C5a, leukotriene B4, platelet-activating factor, and IL-8. The production of the latter chemotaxin by mononuclear phagocytes is especially intriguing as these cells can mediate inflammatory cell migration by either directly generating IL-8, or by inducing its production from surrounding nonimmune cells. In light of these observations, we propose that ischemia reperfusion and oxidant stress, in vivo, may be simulated by anoxia-hyperoxia induced stress in vitro, and that this stress may act as a stimulus for the production of IL-8. We now show that isolated human blood monocytes respond to such an oxygen stress with augmented production of IL-8. In initial studies, monocytes demonstrated an increase in the production of IL-8 under anoxic preconditioning. Subsequently, monocytes were cultured under one of the following conditions for 24 h: (a) room air/5% CO2; (b) 95% N2/5% CO2 for 6 h, followed by room air/5% CO2 for 18 h; (c) 95% N2/5% CO2 for 6 h, followed by 95% O2/5% CO2 for 18 h; (d) room air/5% CO2 for 6 h, followed by 95% O2/5% CO2 for 18 h; or (e) 95% O2/5% CO2. Supernatants were isolated and analyzed for IL-8 antigen by specific IL-8 ELISA, demonstrating the production of monocyte-derived IL-8: 5.9 +/- 0.9, 11.4 +/- 1.7, 21.1 +/- 2.3, 14.6 +/- 2.4, and 26.3 +/- 4.7, ng/ml by designated conditions a, b, c, d, and e listed above, respectively. This variance in IL-8 production reflects altered rates of transcription as shown by Northern blot analysis and nuclear run-off assay. Furthermore, when monocytes were concomitantly treated with LPS (100 ng/ml) under in vitro hyperoxic conditions, both IL-8 steady-state mRNA and antigenic activity were two- to threefold greater than under room air conditions. The association of anoxic preconditioning and oxygen stress with augmented production of monocyte-derived IL-8 support the potential role for ischemia-reperfusion and hyperoxia-induced IL-8 production in vivo, providing a possible mechanism for PMN migration/activation in disease states characterized by altered tissue oxygenation. PMID- 1522236 TI - A fatty neuropeptide. Potential drug for noninvasive impotence treatment in a rat model. AB - Vasoactive intestinal peptide (VIP), a key penile neurotransmitter, induces erection after local injection in man. To augment the therapeutic potential of VIP for impotence treatment and circumvent difficulties of direct penile injections, a strategy was designed to increase peptide hydrophobicity. This was accomplished by the synthesis of a conjugate of VIP and stearic acid (stearyl VIP). Upon penile topical application, stearyl-VIP, in contrast to native VIP, significantly increased sexual function as measured by copulatory activity and penile reflexes (erections) in testosterone-treated, castrated rats. In addition, stearyl-VIP penetrated the body in amounts severalfold greater than VIP. Pharmacokinetic studies demonstrated 10-fold higher penile concentrations of stearyl-VIP, as compared with that measured in the blood 15 min after application, with a gradual decrease thereafter. The peak of incorporation into peripheral tissues that was observed 30 min after administration was 1,000-fold less than that found in the penile tissue. Tissue extraction and chromatographic analysis revealed that stearyl-VIP remained essentially intact for greater than or equal to 15 min and was cleared after 1 h. Thus, topically administered stearyl-VIP had increased bioavailability in comparison with VIP without apparent toxicity, suggesting significant therapeutic potential. PMID- 1522235 TI - Molecular genetics of steroid 5 alpha-reductase 2 deficiency. AB - Two isozymes of steroid 5 alpha-reductase encoded by separate loci catalyze the conversion of testosterone to dihydrotestosterone. Inherited defects in the type 2 isozyme lead to male pseudohermaphroditism in which affected males have a normal internal urogenital tract but external genitalia resembling those of a female. The 5 alpha-reductase type 2 gene (gene symbol SRD5A2) was cloned and shown to contain five exons and four introns. The gene was localized to chromosome 2 band p23 by somatic cell hybrid mapping and chromosomal in situ hybridization. Molecular analysis of the SRD5A2 gene resulted in the identification of 18 mutations in 11 homozygotes, 6 compound heterozygotes, and 4 inferred compound heterozygotes from 23 families with 5 alpha-reductase deficiency. 6 apparent recurrent mutations were detected in 19 different ethnic backgrounds. In two patients, the catalytic efficiency of the mutant enzymes correlated with the severity of the disease. The high proportion of compound heterozygotes suggests that the carrier frequency of mutations in the 5 alpha reductase type 2 gene may be higher than previously thought. PMID- 1522237 TI - Regulation of Ca2+ influx in myeloid cells. Role of plasma membrane potential, inositol phosphates, cytosolic free [Ca2+], and filling state of intracellular Ca2+ stores. AB - To study the mediation of Ca2+ influx by second messengers in myeloid cells, we have combined the whole-cell patch clamp technique with microfluorimetric measurements of [Ca2+]i. Me2SO-differentiated HL-60 cells were loaded with the fluorescent Ca2+ indicator Indo-1, allowed to adhere to glass slides, and patch clamped. Receptor agonists and Ca(2+)-ATPase inhibitors were applied by superfusion and inositol phosphates by microperfusion through the patch pipette. In voltage-clamped cells, [Ca2+]i elevations with a sustained phase could be induced by (a) the chemoattractant receptor agonist FMLP, (b) the Ca(2+) releasing second messenger myo-inositol(1,4,5)trisphosphate [Ins(1,4,5)P3], as well as its nonmetabolizable analogues, and (c) the Ca(2+)-ATPase inhibitor cyclopiazonic acid, which depletes intracellular Ca2+ stores. In the absence of extracellular Ca2+, responses to all stimuli were short-lasting, monophasic transients; however, subsequent addition of Ca2+ to the extracellular medium led to an immediate [Ca2+]i increase. In all cases, the sustained phase of the [Ca2+]i elevations could be inhibited by millimolar concentrations of extracellular Ni2+, and its amplitude could be decreased by depolarization of the plasma membrane. Thus, the sustained phase of the Ca2+ elevations was due to Ca2+ influx through a pathway sensitive to the electrical driving force and to Ni2+. No Ca2+ influx could be observed after (a) plasma membrane depolarization in resting cells, (b) an imposed [Ca2+]i transient independent of receptor activation, or (c) microperfusion of myo-inositol(1,3,4,5)tetrahisphosphate (Ins(1,3,4,5)P4). Also, Ins(1,3,4,5)P4 did not have additive effects when co perfused with a submaximal concentration of Ins(1,4,5)P3. Our results suggest that, in myeloid cells, activation of chemoattractant receptors induces an electrogenic, Ni(2+)-sensitive Ca2+ influx via generation of Ins(1,4,5)P3. Ins(1,4,5)P3 might activate Ca2+ influx directly, or by depletion of intracellular Ca2+ stores, but not via [Ca2+]i increase or Ins(1,3,4,5)P4 generation. PMID- 1522238 TI - Disorders of bile acid metabolism in cholesterol gallstone disease. AB - The aim of the study was to evaluate the metabolism of individual bile acids in patients with cholesterol gallstone disease. Therefore, we determined pool size and turnover of deoxycholic (DCA), cholic (CA), and chenodeoxycholic acid (CDCA) in 23 female gallstone patients classified according to their gallbladder function and in 15 healthy female controls. Gallstone patients had normal hepatic bile acid synthesis, but, depending on gallbladder function, differed with respect to turnover and size of the bile acid pools: Patients with well-emptying gallbladder (group A, n = 9) had enhanced turnover and reduced pools of CA (-46%; P less than 0.01 vs. controls) and CDCA (-24%; P less than 0.05), but normal input and size of the DCA pool. With reduced gallbladder emptying (less than 50% of volume; group B, n = 6), turnover and pools of CA, CDCA, and DCA were similar as in controls. Patients with loss of gallbladder reservoir (group C, n = 8) had increased input (+100%; P less than 0.01) and pool size of DCA (+45%; P = 0.07) caused by rapid conversion of CA to DCA, while the pools of CA (-71%; P less than 0.001 vs. controls) and CDCA (-36%; P less than 0.05) were reduced by enhanced turnover. Thus, in patients with cholesterol gallstones, the pools of primary bile acids are diminished, unless gallbladder emptying is reduced. Furthermore, in a subgroup of gallstone patients, who had completely lost gallbladder function, the CA pool is largely replaced by DCA owing to rapid transfer of CA to the DCA pool. This probably contributes to supersaturation of bile with cholesterol. PMID- 1522239 TI - Electroneutral K+/HCO3- cotransport in cells of medullary thick ascending limb of rat kidney. AB - The renal medullary thick ascending limb (MTAL) of the rat absorbs bicarbonate through luminal H+ secretion and basolateral HCO3- transport into the peritubular space. To characterize HCO3- transport, intracellular pH (pHi) was monitored by use of the pH-sensitive fluorescent probe (2',7')-bis-(carboxyethyl)-(5,6) carboxyfluorescein in fresh suspensions of rat MTAL tubules. When cells were preincubated in HCO3-/CO2-containing solutions and then abruptly diluted into HCO3-/CO2-free media, the pHi response was an initial alkalinization due to CO2 efflux, followed by an acidification (pHi recovery). The pHi recovery required intracellular HCO3-, was inhibited by 10(-4) M diisothiocyanostilbene-2-2' disulphonic acid (DIDS), and was not dependent on Cl- or Na+. As assessed by use of the cell membrane potential-sensitive fluorescent probe 3,3' dipropylthiadicarbocyanine, cell depolarization by abrupt Cl- removal from or addition of 2 mM barium into the external medium did not affect HCO3(-)-dependent pHi recovery, and the latter was not associated per se with any change in potential difference, which indicated that HCO3- transport was electroneutral. The HCO3(-)-dependent pHi recovery was inhibited by raising extracellular potassium concentration and by intracellular potassium depletion. Finally, as measured by use of a K(+)-selective extracellular electrode, a component of K+ efflux out of the cells was HCO3- dependent and DIDS sensitive. The results provide evidence for an electroneutral K+/HCO3- cotransport in rat MTAL cells. PMID- 1522240 TI - Leukemia inhibitory factor is expressed in cartilage and synovium and can contribute to the pathogenesis of arthritis. AB - This study reports on leukemia inhibitory factor (LIF) in human articular connective tissues. Biologically active LIF is present in synovial fluids from patients with osteoarthritis and at higher titers in samples from patients with rheumatoid arthritis. Cultured human synoviocytes and articular chondrocytes produced biologically active LIF and synthesized and secreted LIF proteins that migrated in SDS PAGE at approximately 43 kD. This was increased after stimulation with IL-1 beta. Chondrocytes in serum-containing cultures expressed the 4.2-kb LIF mRNA. IL-1 beta, LPS, and to a lesser extent tumor necrosis factor-alpha induced LIF gene expression. LIF autoinduced its mRNA and this provides evidence for an effect of this cytokine on function of joint tissue cells. Among a series of growth factors tested, transforming growth factor (TGF beta), including the isoforms TGF-beta1, TGF-beta 2, and TGF-beta 3, platelet-derived growth factor, basic fibroblast growth factor, and insulin-like growth factor induced this cytokine gene but differed with respect to the duration of their effects. Cultured synoviocytes expressed the LIF gene in response to the same set of peptide regulatory factors. Analysis of signal transduction pathways showed that PMA increased LIF mRNA, whereas calcium ionophore and cAMP had no detectable effects. Cycloheximide was a potent LIF mRNA inducer and dexamethasone inhibited LIF induced by PMA or IL-1 beta. Cartilage organ cultures and synovial tissues stimulated with IL-1 expressed high levels of LIF mRNA as demonstrated by in situ hybridization. These results identify LIF as a new cytokine that is produced by joint tissue cells and is overexpressed in arthritis. The induction of this cytokine by factors that are present during joint inflammation and the effects of LIF on connective tissue cells suggest that LIF is a mediator that can contribute to the pathogenesis of arthritis. PMID- 1522241 TI - Serum neutralizing antibody response to the vacuolating cytotoxin of Helicobacter pylori. AB - Approximately 50% of Helicobacter pylori isolates produce a cytotoxin in vitro that induces vacuolation of eukaryotic cells. To determine the in vivo relevance of this phenomenon, we sought to detect cytotoxin-neutralizing antibodies in sera from H. pylori-infected persons. As a group, sera from 29 H. pylori-infected patients neutralized the activity of the purified cytotoxin to a significantly greater extent than sera from 24 uninfected persons (P = 0.007). The cytotoxin neutralizing activity in sera from H. pylori-infected persons was mediated predominantly by the purified IgG fraction. Sera from H. pylori-infected persons neutralized the cytotoxins produced by multiple H. pylori strains, but failed to neutralize trimethylamine-induced cell vacuolation. Neutralization of cytotoxin activity by human or immune rabbit sera was associated with immunoblot IgG recognition of an 87-kD H. pylori protein. Similarly, neutralization of the toxin by sera was associated with IgG recognition of the purified cytotoxin in an enzyme-linked immunosorbent assay (P less than 0.0001). The presence of cytotoxin neutralizing antibodies in sera from H. pylori-infected persons indicates that the cytotoxin is synthesized in vivo. PMID- 1522242 TI - Autoantibodies against the amino-terminal cadherin-like binding domain of pemphigus vulgaris antigen are pathogenic. AB - Complementary DNA cloning of the 130-kD pemphigus vulgaris (PV) autoantigen (PVA) has indicated that it is a member of the cadherin family of Ca(2+)-dependent cell adhesion molecules. By homology with typical cadherins, PVA has five extracellular domains (EC1 through EC5). To localize immunogenic domains and to determine whether antibodies against them might be pathogenic, we produced beta galactosidase fusion proteins with cDNA encoding different portions of the extracellular domains of PVA (EC1-2, EC3-5, and each individual domain). Immunoblot analysis of these fusion proteins with 23 PV patients' sera demonstrated that major immunogenic regions of PVA are located on the EC1, EC2, and EC4 domains. IgG was affinity-purified from PV sera on fusion proteins representing the amino (EC1-2) and carboxy (EC3-5) terminus of the extracellular PVA, and injected into neonatal mice. PV IgG affinity-purified on the EC1-2 fusion protein caused suprabasilar acantholysis, the typical histological finding of PV, but IgG affinity-purified on the EC3-5 fusion protein or beta galactosidase alone did not. These results indicate that at least one pathogenic epitope, which is sufficient to cause suprabasilar acantholysis in neonatal mice, is located on the amino-terminal region of PVA, an area thought to be important in cadherin homophilic adhesion. PMID- 1522243 TI - Mechanism of resistance to complement-mediated killing of bacteria encoded by the Salmonella typhimurium virulence plasmid gene rck. AB - We find that pADEO16, a recombinant cosmid carrying the rck gene of the Salmonella typhimurium virulence plasmid, when cloned into either rough or smooth Escherichia coli and Salmonella strains, confers high level resistance to the bactericidal activity of pooled normal human serum. The rck gene encodes a 17-kD outer membrane protein that is homologous to a family of virulence-associated outer membrane proteins, including pagC and Ail. Complement depletion, C3 and C5 binding, and membrane-bound C3 cleavage products are similar in strains with and without rck. Although a large difference in C9 binding was not seen, trypsin cleaved 55.7% of bound 125I-C9 counts from rough S. typhimurium with pADEO16, whereas only 26.4% were released from S. typhimurium with K2011, containing a mutation in rck. The majority of C9 extracted from rck strain membranes sediments at a lower molecular weight than in strains without rck, suggesting less C9 polymerization. Furthermore, SDS-PAGE analysis of gradient peak fractions indicated that the slower sedimenting C9-containing complexes in rck strains did not contain polymerized C9 typical of the tubular membrane attack complex. These results indicate that complement resistance mediated by Rck is associated with a failure to form fully polymerized tubular membrane attack complexes. PMID- 1522244 TI - Binding of uropathogenic Escherichia coli R45 to glycolipids extracted from vaginal epithelial cells is dependent on histo-blood group secretor status. AB - Women with a history of recurrent Escherichia coli urinary tract infections (UTIs) are two to three times more likely to be nonsecretors of histo-blood group antigens than are women without such a history. Further, uroepithelial cells from women who are nonsecretors show enhanced adherence of uropathogenic E. coli compared with cells from secretors. To investigate the hypothesis that nonsecretors express unique receptors for uropathogenic E. coli related to their genetic background, we extracted glycosphingolipids (GSLs) from vaginal epithelial cells collected from nonsecretors and secretors and used an assay in which radiolabeled uropathogenic E. coli were bound to these GSLs separated on TLC plates. An E. coli strain (R45) expressing both P and F adhesins, which was isolated from one of these patients' UTIs, was metabolically labeled with 35S for the TLC binding assay. The radiolabeled E. coli R45 bound to two extended globo series GSLs, sialosyl gal-globoside (SGG) and disialosyl gal-globoside (DSGG), found in the GSL extracts from nonsecretors but not from secretors. The identity of SGG in the nonsecretor GSL extracts was confirmed in radioimmunoassays using an mAb to SGG and in immunofluorescence assays with this mAb and native vaginal epithelial cells. We show that SGG and DSGG are selectively expressed by epithelial cells of nonsecretors, presumably as a result of sialylation of the gal-globoside precursor glycolipid, which in secretors is fucosylated and processed to ABH antigens. The presence of SGG and DSGG may account for the increased binding of E. coli to uroepithelial cells from nonsecretors and for their increased susceptibility to recurrent UTI. PMID- 1522245 TI - Molecular cloning and preliminary characterization of a novel cytoplasmic antigen recognized by myasthenia gravis sera. AB - A cDNA clone was isolated by screening of a lambda gt11 endothelial expression library with serum from a patient with myasthenia gravis (MG). Rabbit antisera raised against the recombinant protein and human MG sera reactive with the clone immunoblotted an M(r) integral of 250,000 polypeptide (gravin) present in endothelial cells and several adherent cells. Gravin was not detected in platelets, leukocytes, U937, or human erythroleukemic (HEL) cell lines, but was expressed in HEL cells after induction with phorbol myristate acetate. Northern blot analysis showed two transcripts of approximately 6.7 and 8.4 kb in endothelial cells but not U937 or HEL cells. Indirect immunofluorescence of permeabilized cells revealed a trabecular network of gravin staining with a distinct linear component. Antibodies to gravin, were present in sera from 22:72 (31%) of MG patients. In contrast 0:50 normal sera and 1:72 sera from patients with other autoimmune diseases contained antigravin antibodies. Gravin is not likely to be a nonerythroid spectrin, talin, myosin, or actin-binding protein based on the lack of reactivity of antigravin with these polypeptides in immunoblots. The nucleotide sequence of the immunoreactive clone indicated that it encodes a highly acidic polypeptide fragment that contains the carboxyl terminus of the protein. Neither amino acid nor nucleotide sequences were present in Genbank, EMBL, or Swissprot databases as of March, 1992. These data indicate that gravin is an inducible, cell type-specific cytoplasmic protein and that auto antibodies to gravin may be highly specific for MG. PMID- 1522246 TI - The melanin-concentrating hormone system of the rat brain: an immuno- and hybridization histochemical characterization. AB - In addition to a nonadecapeptide homologous to the teleost melanin-concentrating hormone (MCH), the amino acid sequence predicted from a rat prepro-MCH (ppMCH) cDNA suggested that at least one (neuropeptide EI, or NEI), and possibly a second (NGE), additional neuropeptide may be encoded by this precursor. Cross-reactivity with epitopes of NEI or NGE can account for reported localization of alpha-MSH, rat CRF, and human GRF in rat dorsolateral hypothalamic neurons. We have used antisera raised against rat MCH and NEI in immunohistochemical studies at the light and electron microscopic levels, along with hybridization histochemical localization of ppMCH mRNA, to define the organization of this system. As expected, ppMCH mRNA is prominently expressed in cells in the lateral hypothalamic area and zona incerta. The MCH and NEI peptides were extensively colocalized in neurons in both of these areas. In addition, smaller cell groups in the olfactory tubercle and pontine tegmentum were also positively hybridized for ppMCH mRNA and immunostained for MCH and NEI. Fibers stained for MCH and NEI were similarly, and very broadly, distributed throughout the central nervous system in patterns that generally conformed with known projection fields of the lateral hypothalamic area and zona incerta. A differential distribution was seen in at least one region, the interanterodorsal nucleus of the thalamus, which contained a prominent terminal field stained for MCH but not NEI. At the electron microscopic level, MCH-stained perikarya displayed a prominent staining associated with the Golgi apparatus; this was not encountered in NEI-stained cells. Both peptides were distributed similarly in terminals in the lateral hypothalamic area and median eminence, with staining associated principally with dense-cored vesicles. The results suggest that ppMCH-derived peptides may serve as neurotransmitters or modulators of prominence in a surprisingly expansive projection field of incerto-hypothalamic neurons. The terminal distributions of this system seem most compatible with functional roles in generalized arousal and sensorimotor integration, processes previously implicated as being subject to modulation by the lateral hypothalamic area. PMID- 1522247 TI - Vagal afferent innervation of the rat fundic stomach: morphological characterization of the gastric tension receptor. AB - Although the gastric tension receptor has been characterized behaviorally and electrophysiologically quite well, its location and structure remains elusive. Therefore, the vagal afferents to the rat fundus (forestomach or nonglandular stomach) were anterogradely labeled in vivo with injections of the carbocyanine dye Dil into the nodose ganglia, and the nerves and ganglia of the enteric nervous system were labeled in toto with intraperitoneal Fluorogold injection. Dissected layers and cryostat cross sections of the fundic wall were mounted in glycerin and analyzed by means of conventional and laser scanning confocal microscopy. Particularly in the longitudinal, and to a lesser extent in the circular, smooth muscle layers, Dil-labeled fibers and terminals were abundant. These processes, which originated from fibers coursing through the myenteric ganglia and connectives, entered either muscle coat and then ran parallel to the respective muscle fibers, often for several millimeters. They ran in close association with the Fluorogold-labeled network of interstitial cells of Cajal, upon which they appeared to form multiple spiny appositions or varicosities. In the myenteric plexus, two different types of afferent vagal structures were observed. Up to 300 highly arborizing endings forming dense accumulations of small puncta similar to the esophageal intraganglionic laminar endings (Rodrigo et al., '75 Acta Anat. 92:79-100) were found in the fundic wall ipsilateral to the injected nodose ganglion. They often covered small clusters of myenteric neurons or even single isolated ganglion cells (mean = 5.8 neurons) and tended to extend throughout the neuropil of the ganglia. In a second pattern, fine varicose fibers with less profuse arborizations innervated mainly the central regions of myenteric ganglia. Camera lucida analyses established that single vagal afferent fibers had separate collaterals in both a smooth muscle layer and the myenteric ganglia. Finally, Dil-labeled afferent vagal fibers were also found in the submucosa and mucosa. Control experiments in rats with supranodose vagotomy as well as rats with Dil injections directly in the distal cervical vagus ruled out the possibility of colabeling of afferent fibers of passage. In triple labeling experiments, in conjunction with Dil labeling of afferents and Fluorogold labeling of enteric neurons, the carbocyanine dye DiA was injected into the dorsal motor nucleus of the vagus to anterogradely label the efferent vagal fibers and terminals. The different distributions and morphological characteristics of the vagal afferents and efferents could be simultaneously compared. In some instances the same myenteric ganglion was apparently innervated by an afferent laminar ending and an efferent terminal.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1522248 TI - Innervation of the amphibian and basilar papillae in the leopard frog: reconstructions of single labeled fibers. AB - Amphibians have two auditory organs specialized for reception of airborne sounds: the amphibian papilla and the basilar papilla. In this report we examine the morphology of the ganglion cells and the afferent innervation of the sensory epithelium in both auditory organs of the leopard frog, Rana pipiens pipiens. Extracellular injections of either biocytin or horseradish peroxidase (HRP) were made into the VIII nerve; they labeled ganglion cells, their axons, and their terminal fibers within the papillae. Ganglion cells that projected to either the amphibian papilla or basilar papilla had cell bodies that were morphologically distinct from other labeled cells. In the amphibian papilla thick fibers terminated in the rostral portion and thin fibers terminated in the caudal portion. Labeled fibers in the rostral portion traveled short distances before making contacts with up to nine hair cells whereas labeled fibers in the caudal portion traveled longer distances and contacted no more than five hair cells. In the basilar papilla labeled fibers were thick (around 4 microns) and terminated on as many as nine hair cells. Consistent with studies from the bullfrog, Rana catesbeiana, our results suggest that the amphibian papilla of R. pipiens pipiens has a convergent innervation (i.e., multiple hair cells provide input to a single ganglion cell) and is topographically organized. However, in contrast to reports in other ranid species, a highly convergent innervation like that found in the amphibian papilla is also found in the basilar papilla. PMID- 1522249 TI - Calcitonin gene-related peptide in afferents to the cat's cerebellar cortex: distribution and origin. AB - In the present study, the distribution and origin of calcitonin gene-related peptide (CGRP) were analyzed in the cat's cerebellum. Following incubation in an antibody generated against rat CGRP and processing with the peroxidase anti peroxidase (PAP) technique, CGRP immunoreactivity (IR) is found in profiles that have morphological characteristics of both simple and complex mossy fibers. However, all mossy fibers are not CGRP-positive. Further, CGRP-IR mossy fibers have a heterogeneous distribution in the cerebellum. In the vermis, the majority of immunoreactive profiles are in lobules VII, VIII, and the dorsal folia of IX. In anterior vermal lobules, only scattered terminals, located primarily at the apex and along the shoulder of the folia, are present. Laterally, CGRP-IR mossy fibers are located in the paramedian lobule, paraflocculus, and crus II. No CGRP fibers or varicosities are observed in any of the cerebellar nuclei. However, CGRP-positive cell bodies are scattered throughout the nuclear neuropil. A double label technique revealed that CGRP-IR mossy fibers arise from neurons located in the lateral reticular nucleus, external cuneate nucleus, inferior vestibular nucleus, and basilar pons. The present findings, taken together with previous data, indicate that cerebellar afferents are chemically heterogeneous. The findings of the present study suggest that precerebellar nuclei that give rise to the mossy fibers that contain CGRP have the potential for playing a complex role in modulating circuitry in the cerebellar cortex of the cat. PMID- 1522250 TI - The rat's postero-orbital sinus hair: II. Normal morphology and the increase in peripheral innervation with adjacent nerve section. AB - The morphology and innervation of the postero-orbital (PO) sinus hair has been studied in normal rats and in adult animals in which an adjacent nerve, the infraorbital nerve, was sectioned on postnatal day 0 or day 7. The normal morphology of the follicle was similar to that of mystacial sinus hairs. However, the normal innervation differed from mystacial follicles in three respects: (1) instead of a separate innervation, the deep vibrissal nerve (DVN) and dermal plexus were supplied by a common follicle and skin nerve, named here the postero orbital cutaneous nerve, a branch of the zygomaticofacial nerve; (2) the entry of the DVN through the capsule was highly variable; in some cases fascicles entered in close proximity, but in others they were widely distributed around the capsule; and (3) two or three small nerves, called here anastomosing nerves, were found to leave the PO follicle. These arose from the DVN after it had passed through the capsule to the cavernous sinus. The anastomosing nerves passed back through the capsule and ascended on the outer surface of the follicle to join the dermal plexus. Each nerve contained 1-4 myelinated fibres and 11-35 unmyelinated fibres. Infraorbital (IO) nerve section on day 0 caused a 19% (P less than 0.001, n = 8) increase in numbers of fibers to the DVN on the lesioned side. Most of the increase was due to unmyelinated fibres with no significant change in myelinated axons. No change in axon numbers in the DVN occurred after day 7 lesions. Labelling of the mystacial pad and the PO follicle did not result in any double labelling of cells in the trigeminal ganglion, in either normal or lesioned animals, making it improbable that the increased numbers of unmyelinated axons arose from rerouting of infraorbital fibres. It is suggested that the increased innervation of the PO follicle may arise by the rescue of ganglion cells from developmentally programmed cell death. PMID- 1522251 TI - Dual innervation of the rat vibrissa: responses of trigeminal ganglion cells projecting through deep or superficial nerves. AB - The rat vibrissal follicle-sinus complex is innervated by a deep vibrissal nerve (DVN) and several smaller fascicles traveling in the dermis [conus or superficial vibrissal nerves, (SVNs)]. The function of the SVNs is unknown, although it has been suggested in a comparative study that they form part of a diffuse, multivibrissal system. Anatomical and electrophysiological methods were used to test this hypothesis and to determine if DVN and SVN fibers have differing response profiles. No ganglion cells were double-labeled after retrograde tracer injections in the DVN and SVNs of single follicles. Electron microscopy showed that selective transection of the DVN caused no SVN degeneration or vice versa. Thus, the dual innervation of the vibrissa arises from separate ganglion cells that project through separate nerves. Ganglion cells with A-row vibrissa receptive fields were studied before and after cutting the DVN and/or SVNs to the responsive vibrissa in order to identify their peripheral trajectories. In this sample, 83% projected through a DVN and 17% via a SVN. SVN or DVN cells were not spontaneously active. All cells responded to single vibrissae only; none were responsive to intervibrissal hairs or skin. Latencies to electrical stimulation were similar for DVN and SVN cells. Adaptation rates and threshold measurements were also similar in the two groups: 60% of the DVN cells and 80% of the SVN cells gave slowly adapting responses to sustained vibrissal displacement; threshold displacements ranged from less than 1 degrees to greater than 15 degrees for both SVN and DVN cells. Direction sensitivity was found in all DVN and SVN slowly adapting cells, with most cells responding to movements in one or two quadrants. For SVN cells, sequential circumferential nerve sections indicated that the fiber's directional sensitivity matched the direction of the fiber's entry into the follicle. The two groups differed in their responses to pushing in or pulling on the hair shaft. All the DVN cells were responsive to both of these stimuli, while for SVN cells pushing activated only 40% and none were responsive to pulling the hair. Another difference in the two groups was that no injury discharges occurred after cutting SVNs, but were present in 44% of DVN cells. These data suggest that DVN and SVNs are similar in the majority of response properties. There is also no evidence to support the hypothesis that SVNs provide diffuse, multivibrissal inputs. PMID- 1522252 TI - Dynamic changes in the density of radial glial fibers of the developing murine cerebral wall: a quantitative immunohistological analysis. AB - The density of radial glial fibers in the developing murine cerebral wall decreases dramatically during the terminal week of gestation. The present analysis characterizes these variations of fiber density quantitatively. Radial glial fibers were stained with monoclonal antibody RC2. Fibers were counted in a standard area of 2,000 microns2, passing orthogonally to the fiber long axis. At E14, fiber density is maximum and relatively uniform throughout the full width of the cerebral wall. Subsequently, the overall glial fiber density decreases and fiber density gradients emerge in the transmural span of fibers. These radial fiber density gradients are marked by sharp declines at the level of the ventricular-subventricular zone and in the zone of transition between intermediate zone (IZ) and cortical plate. In the interval E14-P0, the decrease in densities of fibers crossing the IZ is commensurate with the predicted diluting effects of tissue expansion with growth. By contrast, the decrease in fiber densities in ascent across the cortical plate beyond E14 through E17 exceeds that predicted by growth. The observations suggest that a substantial population of radial glial fibers do not span the full ventricular zone to the cerebral surface. A major contingent appears to extend only as far as the external sagittal stratum/subplate through E16. Subsequently, at a time when supragranular cortical layers are being assembled, the full set of fibers appears to extend more uniformly through the cortical strata. The late surge of fibers would be appropriate to the intercalation of groupings of neurons of the supragranular layers. PMID- 1522253 TI - Development of serotoninlike immunoreactivity in the embryonic nervous system of the snail Lymnaea stagnalis. AB - In our initial effort to study the ontogeny of the gastropod nervous system, we used histological techniques to examine the post-embryonic development of cells which exhibit serotoninlike immunoreactivity in Lymnaea (Croll and Chiasson, J. Comp. Neurol. 230:122-142, '89). The present study complements that report by examining the embryonic development of these neurons. The first serotoninlike immunoreactive (SLIR) cells to be detected in the embryos are the paired C4 neurons of the cerebral ganglia. These cells are faintly visible at about 37-38% of embryonic development and have already produced axons which traverse the cerebral commissure. By about 2-3% later the axon tips reach the pedal ganglia and appose the next SLIR cells to appear, the EPe1 neurons. Over the next 30% of development four more pairs of cerebral neurons are added adjacent to the C4 neurons and over ten cells are added to each of the pedal ganglia. At about 70% of development SLIR fibers are first detected in the parietal and visceral ganglia forming the abdominal ring. Around this time the somata of the C1 neurons also first appear in the cerebral ganglia together with their prominent axons projecting to the buccal ganglia. The last 30% of development is marked by a massive addition of SLIR cells (up to 60) in each pedal ganglion. The early appearance of the first SLIR cells suggests that they may be among the first nerve cells to differentiate and that they may play central roles in the formation of the CNS. We hypothesize that most of the animal's neural circuitry is laid down during embryogenesis by a stereotypic ontogenetic program with post embryonic neurogenesis subserving mostly compensatory and modulatory purposes. PMID- 1522254 TI - All indoleamine-accumulating cells in the rabbit retina contain GABA. AB - The indoleamine-accumulating amacrine cells of the rabbit retina are wide-field and numerous. They form a dense plexus in sublamina 5 of the inner plexiform layer where they make reciprocal synapses with rod bipolar cells. To provide a quantitative test for the colocalization of serotonin (5-HT) and gamma aminobutyric acid (GABA) in the rabbit retina, we designed two parallel double label experiments. In the first series, the indoleamine-accumulating cells were labeled with 5,7-dihydroxytryptamine (5,7-DHT), which was subsequently visualized by photooxidation in the presence of diaminobenzidine. This was combined with autoradiography for 3H-muscimol. In the second and complementary series, 3H-5-HT uptake was combined with postembedding GABA immunocytochemistry. These two experiments provided essentially identical results: over 98% of the indoleamine accumulating amacrine cells were double-labeled. This means that, within the limit of experimental error, all the indoleamine-accumulating amacrine cells are GABAergic. The indoleamine-accumulating amacrine cells account for 15-20% of a large diverse group of GABA amacrine cells. In addition, the rare type 3 indoleamine-accumulating cells and fine processes running in the optic fiber layer were double-labeled. If there is insufficient 5-HT to support a transmitter role in the rabbit retina, our results suggest that the indoleamine-accumulating cells may use GABA as a neurotransmitter. Thus, rod bipolar cells, in common with other bipolar cell types, receive extensive negative feedback at GABA-mediated reciprocal synapses. PMID- 1522255 TI - 75 years of Radon transform. PMID- 1522256 TI - Determination of liver volume from CT scans using histogram cluster analysis. AB - The histogram cluster analysis procedure (HICAP), which was developed by NASA for processing satellite images, classifies images into discrete clusters of pixels according to one or more arbitrary imaging variables. We incorporated this nonparametric, multivariate procedure in a semiautomatic computer algorithm for calculating total liver volume from CT scans and compared its performance with that of a human observer. Total liver volumes were calculated from CT scans in adult patients by the algorithm and by an experienced radiologist using the trackball controlled cursor at the CT console. Variability in the computer calculated volumes was determined by repeating calculations three times over the course of 3-12 months. Using HICAP in the univariate mode, we calculated total liver volumes from 28 contrast enhanced CT scans in 27 patients. Liver volumes calculated by the semiautomatic and manual methods had a median absolute difference of 3.6% (Vcomputer = 1.08 * Vmanual - 99.52 cc; r2 = 0.99). Median day to-day variability of the computer calculated volumes was 1.9% (95% confidence interval: 1.3-2.7%). Using HICAP in a bivariate mode to illustrate its ability to incorporate two image features in one analysis, we studied an additional patient and compared total liver volume calculated from the univariate data set defined by the contrast enhanced CT scan with that calculated from the bivariate data set defined by nonenhanced and contrast enhanced CT scans. The HICAP errors were 4.1% in the univariate analysis and 0.4% in the bivariate analysis. It is concluded that this statistical clustering algorithm provides a clinically accurate, repeatable, and feasible method of in vivo liver volume determination. PMID- 1522257 TI - Quantification of glucose utilization in liver metastases: parametric imaging of FDG uptake with PET. AB - Positron emission tomography (PET) fluorodeoxyglucose (FDG) studies are useful for identifying foci of increased FDG uptake in liver metastases, because of the high glycolytic rate of malignancies, as well as for monitoring changes in tumor glucose metabolism during treatment. We performed 15 kinetic PET FDG studies in four patients with metastatic liver disease. We produced parametric images of glucose metabolism in terms of the rate constant K (ml/min/g) for net phosphorylation of FDG. Tumor K values, estimated with nonlinear regression, correlated well with K values estimated with Patlak graphical analysis (r = 0.96), validating the assumption of low k4* values in liver metastases and supporting the use of pixel by pixel Patlak plot analysis of the data to generate parametric images. In normal liver, high levels of glucose-6-phosphatase produce much higher values of k4* than in liver metastases. Uncorrected Patlak graphical analysis underestimates K in normal liver, but this further increases the contrast between tumor and liver and facilitates both tumor detection and quantification. The technique is computationally feasible and is well suited for serial evaluations of tumor metabolism during treatment. PMID- 1522258 TI - Role of contrast agent perfusion and of diffusion in the NMR signal enhancement of liver lesions. AB - Both perfusion and diffusion contribute to NMR signal enhancement after intravenous injection of a nonspecific contrast agent. In the present study the roles of perfusion and diffusion in the contrast enhancement of induced liver lesions in the rat and the rabbit were evaluated. This was done by comparing Gd DOTA absolute enhancement signal-to-noise versus time plots of various lesions with the findings from microangiography and histology. Four types of enhancement could be recognized. Diffusion was the major factor in the delayed enhancement seen in lesions that had large extravascular diffusion space. PMID- 1522259 TI - Castleman disease mimicking liver tumor: CT and MR features. AB - We report the CT and MR features of two localized abdominal forms of Castleman disease mimicking hypervascular liver tumors due to their unusual location in the porta hepatis and the portacaval space. The MR appearance of Castleman lymph nodes is emphasized, including their characteristics on dynamic turbo-fast low angle shot (FLASH) sequences after Gd-DOTA bolus injection. Our report suggests that the CT and MR features of Castleman lymph nodes in these locations cannot enable their differentiation from other hypervascular masses such as benign liver tumors. PMID- 1522260 TI - Direct invasion of urinary bladder from sigmoid colon cancer: CT findings. AB - Radiological findings in three cases of sigmoid colon carcinoma invading the urinary bladder are reported. An irregular spiculated margin or nodular indentations in region of bladder dome were seen on intravenous urography. A soft tissue mass contiguous with an irregularly thickened urinary bladder wall and a circumferentially thickened sigmoid colon wall were demonstrated on CT and sonography and led to the correct diagnosis. PMID- 1522261 TI - Diagnosis of pneumoperitoneum: abdominal CT vs. upright chest film. AB - To compare the sensitivity of CT with upright chest radiography for the detection of free intraperitoneal air, we compared the results of these examinations performed on trauma patients who had introduction of intraperitoneal air from diagnostic peritoneal lavage (DPL). Thirteen patients were studied by abdominal CT within 24 h after DPL. Upright chest radiography was performed prior to abdominal CT or less than 4 h after abdominal CT. All patients demonstrated free air on abdominal CT. Only 5 of 13 (38%) patients demonstrated free air on plain radiography. The amount of free air demonstrated on CT was quantified into three groups. Upright chest radiography in the minimal group (less than three 1 mm pockets of air) was totally insensitive (0 of 2) in detecting free air. Upright chest radiography in the moderate group (greater than three 1 mm pockets, but less than 13 mm diameter collection of air) was 33% sensitive (3 of 9). Upright chest radiography in the large group (greater than 13 mm collection of air) was 100% sensitive (2 of 2). Abdominal CT is clearly superior to upright chest radiography in demonstrating free intraperitoneal air in this clinical setting. PMID- 1522262 TI - Abdominal CT scans in patients with blunt trauma: low yield in the absence of clinical findings. AB - This study undertook to determine the yield of abdominal CT scans ordered only because the patient's sensorium was decreased or general anesthesia was planned. The abdominal CT scans and hospital charts of 191 consecutive patients examined following blunt trauma were reviewed with respect to clinical indications prompting the study. In 143, some clinical or laboratory justification was in evidence. In this group, 55 patients (38.5%) were found to have trauma-related pathology at CT scan. In 48 patients, no clinical or laboratory suggestion of abdominal pathology was evident. Instead, the primary indications for ordering the CT scan were decreased sensorium (28 cases), the planning of general anesthesia for orthopedic procedures (8 cases), and a variety of non-abdominal trauma-related reasons. In this group, only a single positive finding was identified (small pneumothorax), and in no case was the clinical course altered by findings at abdominal CT scan. Performance of abdominal CT scans without clinical or laboratory evidence of trauma, merely because of decreased patient sensorium or prophylactically prior to general anesthesia for non-abdomen-related surgery, is an extremely low yield study and should be discouraged. In the current study, no significant abdominal pathology would have been overlooked by omission of such scans. Similar findings have been reported in children. To our knowledge, this is the first such report in a largely adult population. PMID- 1522263 TI - CT features of benign and malignant teratomas in children. AB - Computed tomography of 15 pediatric patients with teratomas of the chest, abdomen, and pelvis was reviewed to compare the features of benign and malignant lesions. Particular attention was paid to the frequency of characteristic CT features of this lesion, namely fat, calcification, and mural nodules. Of the 10 benign masses, 8 were predominantly cystic, usually containing less than 10% soft tissue components. One benign lesion was complex and one was nearly solid. Fat was found in 9 of 10 lesions (90%), calcification in 7 (70%), and mural nodules in 7 (70%). All five malignant teratomas were predominantly solid, containing primarily soft tissue contents. Approximately 80% of malignant tumors had CT evidence of local invasion or distant metastases. Three of five malignant lesions (60%) contained calcifications and two of five (40%) had fat. None had recognizable mural nodules. Our experience suggests that typical CT features of teratomas occur more often in benign than in malignant lesions. PMID- 1522264 TI - Chemical shift and the double-line sign in MRI of early femoral avascular necrosis. AB - The double-line sign (DLS) on T2-weighted images in femoral avascular necrosis (AVN) is formed by a high-intensity rim at the reactive interface inside a low intensity margin. A hypothesis has been advanced that the sign may be seen in early AVN whether or not there is bony sclerosis. On change of direction of the frequency-encoding axis, the high-intensity area rimmed with low-intensity margin was generated on the side where chemical shift misregistration artifact was seen. Transposition of frequency-encoding and phase-encoding axes yielded the same results. The thickness of the low-density rim was almost equal to the amount of expected offset distance due to chemical shift misregistration. Therefore, chemical shift misregistration artifact is the most reasonable explanation for the DLS observed in early femoral AVN. PMID- 1522265 TI - Volume T1-weighted gradient echo MRI in multiple sclerosis patients. AB - Three-dimensional (3D) volume turbo fast low angle shot (FLASH) techniques have become available which produce heavily T1-weighted images, similar to inversion recovery scans, utilizing the appropriate flip angle and inversion time. The purpose of this study was to compare the sensitivity of a rapid volume gradient echo technique [3D magnetization prepared rapid acquisition gradient echo (MP RAGE)] in identifying multiple sclerosis (MS) plaques with a conventional T2 weighted spin echo (SE) sequence. Ten patients with clinical MS were evaluated. Patients underwent a routine examination consisting of an axial T2-weighted SE sequence (2,500,22/90) and a coronal 3D MP RAGE, 10/4/10, acquired as 128 two mm partitions. In six patients, area measurements of 22 plaques were determined on both the axial T2-weighted SE examinations and the axial reformatted MP RAGE examinations. The overall number of plaques utilizing each technique was approximately the same. One hundred twenty-two plaques were visualized for the 3D MP RAGE sequence, and 128 plaques for the T2-weighted SE sequence. There were differences in detection of plaques in different regions, with plaques in gray matter better demonstrated utilizing the conventional T2-weighted SE sequence. Plaques in the corpus callosum, pons, and brachia pontis were better demonstrated utilizing 3D MP RAGE. No significant difference was found between the areas measured on the MP RAGE sequence and on the T2-weighted SE sequence. Three dimensional MP RAGE provides a sensitive and complementary method to conventional T2-weighted SE sequences in the evaluation of patients with MS. PMID- 1522266 TI - Comparison of skull circumference and linear measurements with CSF volume MR measurements in hydrocephalus. AB - In children with hydrocephalus, accurate and reproducible estimation of the presence, severity, and course of the condition is of paramount importance for both clinical and scientific purposes. In this study, 30 hydrocephalic patients were assessed with a number of commonly used methods, such as occipitofrontal skull circumference (SC) measurements, Evans ratio (ER), and bicaudate index (BCI), as well as, for comparison, another ratio of linear measurements [ventricle-skull ratio (VSR)] and MR measurements of total intracranial CSF volume. In repeated CSF volume measurements in healthy volunteers, the MR method appeared to be accurate and reproducible. This technique was simpler and easier in application, requiring less interaction than comparable MR techniques described by others. The variation coefficients were within the same range. In increased CSF volumes, our technique can be recommended; in very small CSF volumes, another technique is more adequate. Direct assessment of CSF volume as a measure of hydrocephalus was preferable over derived estimations for scientific purposes and may function as a gold standard against which to evaluate other techniques that are easier to apply clinically. In comparison, SC measurements were poor; CSF volume changes were not reflected in SC changes. VSR was preferable over ER and BCI, because it correlated more closely with CSF volume. PMID- 1522267 TI - Differentiation of suprasellar nonneoplastic cysts from cystic neoplasms by Gd DTPA MRI. AB - Magnetic resonance imaging in 9 cases of surgically confirmed nonneoplastic intra and/or suprasellar cysts was analyzed and compared with that from 17 cases of craniopharyngioma and 12 of cystic pituitary adenoma. Signal intensity did not help in distinguishing nonneoplastic cysts from cystic neoplasms. No postcontrast (Gd-DTPA) cyst wall enhancement was observed among the nonneoplastic cysts, although all 6 craniopharyngiomas and 12 cystic pituitary adenomas that underwent postcontrast study did enhance. Three nonneoplastic cysts were surrounded by the pituitary gland, thus mimicking wall enhancement in the postcontrast studies. Rapid enhancement in the early postcontrast-administration phase (dynamic studies) helped avoid confusion between the normal pituitary tissue and cyst wall enhancement. Magnetic resonance studies with contrast enhancement play an essential role in differentiating nonneoplastic cysts from cystic neoplasms in the sella region. PMID- 1522268 TI - Cerebrovascular reserve capacity in ischemia due to occlusion of a major arterial trunk: studies by Xe-CT and the acetazolamide test. AB - Classifications based on clinical and radiographic criteria have proved to be inadequate predictors of the course of cerebral ischemia or its response to therapy. In this study the cerebrovascular reserve capacity (CRC) of 46 patients with symptomatic cerebrovascular ischemia was studied by stable xenon-enhanced CT (Xe-CT) combined with the acetazolamide test. Fifteen patients had internal carotid artery (ICA) occlusion, 10 had ICA stenosis, 10 had middle cerebral artery (MCA) occlusion, and 11 had MCA stenosis. In the patients with chronic cerebral ischemia due to occlusive lesions of the ICA and MCA, the CRC was reduced most in those with MCA occlusion, followed, in descending order, by those with ICA stenosis, MCA stenosis, and ICA occlusion. Our results indicate that measurement of the CRC elucidates cerebral hemodynamic factors that cannot be detected by angiography in patients with chronic cerebral ischemia and that Xe-CT combined with the acetazolamide test is useful for this purpose. PMID- 1522269 TI - Demonstration of subclavian steal by MR angiography. AB - We present three cases of subclavian steal syndrome demonstrated by MR angiography. By using a presaturation pulse located at the bottom or at the top of the acquisition volume we demonstrated the flow direction of vertebral arteries. We used a new investigational two-dimensional time-of-flight sequence. PMID- 1522270 TI - Gd-DTPA enhanced MRI of cervical anterior epidural venous plexus. AB - Seventy selected cases were reviewed retrospectively to assess the normal Gd-DTPA enhanced MR appearance of the cervical anterior epidural venous plexus. This structure can enhance quite markedly and has a somewhat variable appearance on MR imaging but we believe that it can be differentiated from pathological enhancement in the area if attention is paid to its normal anatomical characteristics. PMID- 1522272 TI - Orbital blowout fractures as a cause of sinonasal obstructive disease. AB - Six cases of orbital blowout fracture with inferomedial herniation of orbital contents into the sinonasal ostiomeatal unit causing obstruction to maxillary sinus outflow are presented. Potential hazards during endoscopic sinus surgery in these cases are outlined. PMID- 1522271 TI - Retrospective fusion of radiographic and MR data for localization of subdural electrodes. AB - Prior to epilepsy surgery, subdural electrodes are often implanted and monitored for a few days to identify the focus of abnormal electrical activity. During the implantation and subsequent brain resection, there may be uncertainty about the exact location of the electrodes with respect to features of brain anatomy such as specific gyral convolutions or lesions. In experiments with a phantom and patients, implanted electrodes were imaged with multiplanar skull radiographs (or CT scans). After retrospective registration with preimplantation MR data, the electrodes were mapped from these studies onto an MR-derived three-dimensional brain model. The resulting multimodality displays showed the relationship of the electrodes to brain anatomy. In one patient the position of each electrode with respect to a metabolic lesion was also displayed by mapping preimplantation PET data onto the same brain model. This new display of electrode positions may strengthen the interpretation of subdural electrical recordings and thereby reduce uncertainty in planning the resection of epileptic tissue. PMID- 1522273 TI - Evaluation of high-resolution CT after tympanoplasty. AB - The temporal bones of 28 patients who underwent tympanoplasty were evaluated with high-resolution CT (HRCT). Seventeen patients had undergone tympanoplasty with a columella, used to form an ossicular reconstruction. The incus body was used as the columella in 4 patients and a prosthesis was used in 13 patients. No columella was used in the other 11 patients. After tympanoplasty, CT demonstrated normal appearance in 8 patients. Of the other 20 patients, 16 were diagnosed with chronic otitis media, and 4 were diagnosed with recurrent cholesteatoma on the basis of follow-up CT examinations. Seven underwent reoperation. In all 4 patients with recurrent cholesteatoma, the diagnosis was pathologically confirmed at reoperation. In 1 patient diagnosed with chronic otitis media, the pathological diagnosis was recurrent cholesteatoma. The columellae in 8 of the 17 patients could not be identified on CT because of surrounding soft tissue mass, but in the other 9 patients the condition of the ossicular reconstruction was well demonstrated. Prosthesis dislocation was apparent in 2 patients. We recommend HRCT examination in the follow-up of tympanoplasty patients. PMID- 1522274 TI - Temporal correlation images derived from sequential MR scans. AB - In this paper a new technique is presented for measuring the local temporal changes and correlation between them on spatially aligned image sequences. A temporal correlation image is derived from a sequence of static images (frames). The method is illustrated in an application to the dynamic MRI of the rabbit kidney following bolus injection of Gd-DTPA. The similarity maps clearly separate the dynamic response of the cortex to the indicator from that of the medulla and, therefore, segment the kidney into two regions. Regions with different temporal dynamics can be displayed in different colors using a lookup table designed for that purpose. PMID- 1522275 TI - Cardiac flow measurement by ultrafast CT: validation of continuous and pulsatile flow. AB - To gauge the accuracy of ultrafast CT in measuring cardiac output and myocardial perfusion in humans, measurements of continuous and pulsatile flow were made in a large asymmetrical phantom. The variation in the relationship between Hounsfield number and contrast concentration was assessed in a human thorax phantom. Radiopaque contrast medium was injected during perfusion of the phantom at a range of flow rates between 1.5 and 8 L/min. The phantom was scanned in two modes (50 and 100 ms) during continuous and pulsatile flow and with the phantom surrounded by air and by water. Flow in the tubes was calculated using indicator dilution theory, and flow in the tissue-equivalent chamber was calculated by applying first-pass distribution principles. The standard deviation of the difference between calculated and measured flow varied from 0.2 to 0.6 L/min, giving 95% limits of agreement from 0.4 to 1.2 L/min. The constant (K) relating Hounsfield unit number to iodine concentration varied widely both in different locations within the phantom and under different scan conditions (17.2-27.6 HU/mg I). Within a human thorax phantom, K varied from 14.15 to 23.18 HU/mg I and was dependent on location within the thorax phantom, the scan mode, and the cross sectional diameter of the phantom. These data suggest that though the ultrafast CT scanner can measure continuous and pulsatile flow accurately in tubes, precise measurements of cardiac output in humans will require K to be assessed for each subject. Measurements of flow in tissue should be possible. PMID- 1522276 TI - Performance evaluation of the positron scanner ECAT EXACT. AB - The Cologne Special is a prototype of the ECAT EXACT (model 921), a new generation of Siemens-CTI PET scanners. It consists of three rings of 48 BGO block detectors each, covering an axial field of view of 16.2 cm with a patient port of 56.2 cm diameter. This results in a total of 24 rings with 384 crystals each, giving 47 contiguous image planes in two-dimensional (2D) mode. Total system sensitivity is 216 kcps/microCi/ml for a 20 cm cylinder phantom in 2D. This increases to 1.5 Mcps/microCi/ml in 3D. Data are acquired in the stationary mode only (no wobble motion), resulting in a transaxial spatial resolution of better than 6 mm full width at half-maximum (FWHM) at the center, which degrades to 7.5 mm tangentially and 9.6 mm radially at a radius of 20 cm. Average axial resolution changes from 5.0 mm FWHM at the center to 8.1 mm at R = 20 cm. Count rate performance was investigated at different low energy discriminator settings and found to be linear up to 2.5 microCi/ml with a 20 cm phantom. The magnitude and distribution of scatter were evaluated for both septa-extended and septa retracted conditions for a range of energy thresholds. Brain, heart, and whole body studies with the new tomograph demonstrate the versatility of its applications without compromising on physical performance. PMID- 1522277 TI - Complex partial seizure-induced transient MR enhancement. AB - A 58-year-old man with complex partial seizures had transient symmetrical MR enhancement in the anterior mesiotemporal cortex bilaterally, correlated with the sites of seizure focus on electroencephalography. Preinfused T1-weighted and T2 weighted sequences showed no abnormality. After adequate control of seizures with medication, repeat MR was normal and the prior enhancement was no longer seen. This transient seizure-induced MR enhancement was consistent with ictal or postictal hyperemia and breakdown of the blood-brain barrier and should not be erroneously attributed to mesial temporal sclerosis, encephalitis, tumor, or infarction. PMID- 1522278 TI - Spinal cord toxoplasma lesion in AIDS: MR findings. AB - Toxoplasma gondii is the cause of the most common opportunistic infection of the brain in AIDS but is extremely rare as the cause of a solitary lesion of the spinal cord. Symptoms are weakness of the lower limbs followed closely by paralysis unless diagnosed and treated early. We present such a case in an intravenous drug abuser with AIDS and emphasize that MRI is the diagnostic tool of choice and that the index of suspicion should be high in immunosuppressed patients. PMID- 1522279 TI - MRI and neurological complications of adult T-cell leukemia/lymphoma. AB - We report the assessment by MRI of a lumbosacral lymphomatous localization of adult T-cell leukemia/lymphoma (ATLL) with human T-cell lymphotropic virus-1 infection in an African patient. Brain MRI detected associated multifocal lesions of increased signal intensity in the subcortical white matter. These MRI abnormalities are compatible with reported necropsy findings in cases of ATLL with neurological complications. PMID- 1522280 TI - Spinal cord MRI in adult polyglucosan body disease. AB - MRI appearance of adult polyglucosan body disease is described. A 67-year-old man presenting with a chronic progressive degenerative neurologic disorder was found to have marked atrophy of the entire cord, without signal abnormalities on long TR images. Autopsy revealed atrophy of the cord, diffuse gliosis, and numerous corpora amylacea. PMID- 1522281 TI - CT "halo sign" in pulmonary tuberculoma. AB - The CT halo sign has been described as the CT finding of a low-attenuation zone surrounding a pulmonary nodule. It is an early clue to the diagnosis of invasive pulmonary aspergillosis. We describe a case of CT halo sign associated with a pulmonary tuberculoma. Therefore, we think that a diagnosis other than invasive pulmonary aspergillosis should be considered in the presence of the CT halo sign in immunocompetent patients. PMID- 1522282 TI - Fitz-Hugh-Curtis Syndrome: pelvic inflammatory disease with an unusual CT presentation. PMID- 1522283 TI - Radiography, US, and CT of acupuncture needles in the abdominal organs. PMID- 1522284 TI - Ultrasound and CT of a calcified testicular Leydig cell tumor. PMID- 1522285 TI - Studies of fluoride retention by oral soft tissues after the application of home use topical fluorides. AB - Previous studies have focused on enamel and plaque as the primary sites of fluoride (F) retention in the mouth. The present study was undertaken to evaluate the role of oral soft tissue as a site of F retention by comparing an edentulous subject panel (n = 9) with a fully dentate panel (n = 10). Unstimulated whole saliva samples were collected by having subjects pool saliva for two min. Samples were collected over a 24-hour period after application of a placebo dentifrice (PD; 0.4 ppm F), fluoride dentifrice (FD; 1100 ppm F), fluoride rinse (FR; 226 ppm F), or fluoride gel (FG; 5000 ppm F) delivered in custom trays. There was no statistically significant difference in salivary flow rate between the two panels for any of the treatments. The edentulous panel had higher salivary F levels than the dentate panel, which reached statistical significance (p less than 0.05) for the FD and FG treatments. In a separate study involving the same treatments, F levels at specific soft-tissue sites were measured over a one-hour period by use of absorbent discs placed in different soft-tissue areas of the mouth. The tongue and lower posterior vestibule retained the highest F levels, followed by the upper posterior buccal vestibule and upper anterior labial vestibule, with the lowest F levels retained in the lower anterior vestibule and the floor of the mouth. There was a strong-to-moderate correlation between whole saliva F concentration and F levels at specific soft-tissue sites. This study establishes the importance of oral soft tissue as the major site of F retention in the mouth. PMID- 1522286 TI - Distribution of fluoride in saliva and plaque fluid after a 0.048 mol/L NaF rinse. AB - An ultramicro method has recently been described for measurement of plaque-fluid fluoride concentration (Vogel et al., 1990a). This method was used: (1) for exploration of the variation in fluoride concentration of plaque fluid collected from the same buccal tooth sites following a 0.048 mol/L NaF (0.2%) rinse, and (2) for examination of the distribution of fluoride in plaque fluid and saliva within one hour after this rinse. Results indicated an average coefficient of variation (CV) of 31% for plaque-fluid fluoride in triplicate samples recovered simultaneously from the buccal-proximal region of two teeth after the rinse. This was similar to the CV found for plaque-fluid fluoride from the same sites after separate administrations of the rinse. A strong linear correlation was found between salivary and plaque-fluid fluoride at 30 and 60 min after rinse administration, showing that plaque-fluid fluoride is influenced by the concentration of salivary fluoride after administration of this rinse. Plaque fluid fluoride concentrations were higher than that in saliva at baseline, 30, and 60 min. Very large inter-site and intersubject variations in plaque-fluid distribution were observed, with the central incisors showing the slowest clearance. These variations suggest that an examination of plaque-fluid fluoride from specific tooth regions may be essential for understanding the effects of fluoride on the site-specificity of caries. PMID- 1522287 TI - Fluoride retention in dentin after topical application of aminefluoride. AB - The retention of KOH-soluble and structurally bound fluoride in dentin after topical application of aminefluoride was investigated. One cylindrical dentin sample was prepared from each of 40 extracted third molars. All samples received one topical application of 1 microL of aminefluoride solution (1.23% F) for three min. Ten of them were analyzed immediately after fluoridation. The remaining 30 samples were mounted in the buccal aspects of a special mouth application which was carried by a person for five days. After one, three, and five days, 10 of the 30 samples were removed from the appliance. In all samples, the amount of structurally bound fluoride was determined in three layers (20 microns, 20 microns, 20 microns) by use of a special grinding technique. Before each grinding step, the dentin specimens were analyzed for KOH-soluble fluoride. The total amount of KOH-soluble fluoride in dentin was 48.7 +/- 14 micrograms/cm2. It decreased drastically during the experimental period. Structurally-bound fluoride increased one day after fluoridation in the first and second layers. Thus, topical application of aminefluoride resulted in a significant accumulation of KOH-soluble fluoride in dentin. This precipitate was unstable, but fluoride ions released from it could perhaps increase the amount of structurally bound fluoride. PMID- 1522288 TI - Inhibition of plaque formation and gingivitis in beagle dogs by topical use of a degradable controlled-release system containing chlorhexidine. AB - The in vivo efficacy of a newly-developed dental application of a film-forming, chlorhexidine-containing system was examined in beagle dogs. A self disintegrating film-forming solution was applied three times weekly to the dentitions of 7 out of 13 dogs, which were fed a soft-food diet. Plaque accumulation (Plaque Index) and gingival inflammation (Gingival Index) were recorded at one, two, four, six, and eight weeks. The local delivery of low-dose chlorhexidine to dogs significantly inhibited gingivitis and plaque formation. It is concluded that the dental application of a film-forming system may be a preferable method of periodontal disease prophylaxis, and may enhance supragingival plaque control in areas of isolated periodontal problems associated with obvious local predisposing factors. PMID- 1522289 TI - Effects of chlorhexidine-containing gel and varnish on abutment teeth in patients with overdentures. AB - Previous experiments have shown that daily use of 1% chlorhexidine gel strongly reduced caries development in the abutment teeth under overdentures. The present experiment was designed to determine whether intermittent application of chlorhexidine, either in a varnish or in a gel, might be used as an alternative preventive method, less demanding for the patient. To this end, 31 patients were distributed among four treatment groups, with the number of mutans streptococci in plaque and saliva used as a balancing criterion. The treatments consisted of a single application of 40% chlorhexidine varnish, daily application of 1% chlorhexidine gel for one week, or the corresponding placebo treatments with varnish or gel without chlorhexidine. Patients were re-called for bacteriological and clinical examination at various intervals during an eight-week period following treatment. Chlorhexidine varnish and chlorhexidine gel applications significantly suppressed mutans streptococci on the abutment teeth for four and eight weeks, respectively. In agreement with earlier findings, the numbers of Actinomyces viscosus/naeslundii in plaque were significantly increased after chlorhexidine varnish treatment. The chlorhexidine gel reduced plaque accumulation and gingival bleeding for one week but had no long-lasting effect. The results seem to justify a long-term clinical test of intermittent chlorhexidine applications as an alternative for daily use in patients with overdentures. PMID- 1522290 TI - Distribution of chondroitin sulfate and dermatan sulfate in normal and inflamed human gingivae. AB - The effect of inflammation on the distribution of chondroitin sulfate and dermatan sulfate proteoglycans was assessed after normal and inflamed human gingivae were stained with monoclonal antibodies against these extracellular matrix macromolecules. The tissues were obtained following periodontal surgery and reacted with specific antibodies after pre-treatment with chondroitinase ACII or chondroitinase ABC, and staining was visualized by the immunoperoxidase technique. The results indicated that these two proteoglycans were present in both the 4-sulfated and 6-sulfated isomeric forms. While chondroitin sulfate appeared to be uniformly distributed throughout the connective tissue, dermatan sulfate showed greater intensity of staining in the areas immediately subjacent to the epithelium. Positive staining for chondroitin sulfate was noted in the intercellular spaces of the epithelium. In inflamed tissues, there was significant staining associated with 4-sulfated dermatan sulfate and chondroitin sulfate, but this had lost the structured pattern of staining noted in normal sections. The 6-sulfated isomeric forms were greatly reduced in inflamed tissues and tended to show a predilection to be localized within the perivascular tissues. In the inflamed tissues, there was intense staining for chondroitin sulfate associated with the infiltrating inflammatory cells. These findings corroborate earlier biochemical studies on normal and inflamed gingival tissues. The specific tissue localization of dermatan sulfate and chondroitin sulfate in tissues damaged by inflammation indicates that, as opposed to the large loss of collagenous material noted during inflammation, there is not a corresponding large loss of proteoglycan. Indeed, at specific inflammatory foci, the intensity of staining for these macromolecules may intensify. PMID- 1522291 TI - Radiometric classification of alveolar bone health. AB - A radiograph-based classifier for discrimination between normal and diseased alveolar bone was developed. The alveolar bone health of dry mandibles was rated, by consensus of two trained observers, as normal or diseased. Bitewing radiographs of mandibular quadrants were digitized and regions of interest (ROIs) of the alveolar bone between the first and second permanent molars outlined. Gray scale histograms for the ROIs were computed, and a classifier based on these histograms was developed. Two observers (independently) used only the classifier to rate the bone as being normal or diseased. These ratings were compared with the original ratings of trained observers who viewed and scored the actual alveolar bone. The sensitivity (the ability to detect diseased alveolar bone), specificity (the ability to detect normal alveolar bone), and accuracy were 0.90 or greater, indicating good agreement with subjective visual assessments of dry mandibles. These results suggest that this procedure may be applicable for evaluations of bone health in humans. PMID- 1522292 TI - Staircase assessment of the magnitude and time-course of 50% nitrous-oxide analgesia. AB - The analgesic effect of 50% nitrous oxide and oxygen on thermal pain sensations was evaluated in a placebo-controlled, double-blind crossover design. In a session immediately before oral surgery, 20 patients used a seven-point verbal scale to rate the intensity of pain sensations evoked by three-second thermal stimuli delivered to 14 sites on the volar forearm at 20-second intervals by a 1 cm-diameter contact thermode. Subjects rated 36 stimuli while breathing room air and then two additional sets of 36 stimuli while inhaling 50% nitrous oxide and oxygen during one set and oxygen placebo during the other. Each of these two stimulus sets was preceded by a two-minute induction of the agent, and the sets were separated by a three-minute washout period. Order of administration was randomized and counterbalanced. Stimulus temperatures were adjusted continuously by an interactive computer program so that response could be maintained at predetermined levels. This method resulted in a continuous measure of analgesia in units of stimulus intensity. Results showed that, in comparison with placebo, nitrous oxide significantly increased the stimulus temperatures (mean = 0.42 degrees C) required to make the same response [F (11,209) = 6.76, p less than 0.0001], indicating analgesia. This increase was one-third to one-half that observed with clinical doses of intravenous fentanyl. Analgesic effects were apparent at three min and wanted 10 min after termination of nitrous-oxide inhalation. These times closely correlated with previous measures of alveolar concentration, further supporting the fast but modest analgesic action of nitrous oxide. PMID- 1522293 TI - Effect of 45,X/46,XX mosaicism on root morphology of mandibular premolars. AB - The effect of X chromosome mosaicism on root morphology of mandibular premolars was studied in 14 females with 45,X/46,XX chromosome constitution. Occurrences of two-rooted premolars and the morphology of the roots were examined from orthopantomograms. Six (43%) of the 45,X/46,XX mosaics had two-rooted mandibular premolars. Two-rooted first premolars were found in four (29%) and second premolars in three (21%); in one, all four mandibular premolars were two-rooted. The results indicate that the frequency of two-rooted mandibular premolars was similar in 45,X/46,XX mosaics and in 45,X females, and in both groups significantly higher than in normal 46,XX females. Compared with 45,X females, the 45,X/46,XX mosaics showed a slight tendency toward more simplified root morphology in the first premolars. The findings suggest that the presence of normal 46,XX cells among the defective 45,X cells does not affect the development of the mandibular premolar roots. Furthermore, the results do not support the earlier proposal that the presence of normal 46,XX cells in 45,X/46,XX mosaic individuals would be reflected in gradual normalization of dental development. PMID- 1522294 TI - Demand and need for treatment of craniomandibular dysfunction in the Dutch adult population. AB - A nationwide survey of oral conditions, treatment needs, and attitudes toward dental health care in Dutch adults was carried out in 1986. One of the aims of the study was to investigate the perceived need and demand for treatment of craniomandibular dysfunction (CMD). A sample of 6577 persons (15-74 yrs of age), stratified for gender, age, region, and socio-economic status, was contacted. Of this sample, 4496 persons participated in the behavioral part of the study, of which 3526 were examined clinically. The CMD-treatment demand was based on (1) CMD complaints in the past, (2) CMD complaints at present, and (3) an anticipated increase of the present complaints. CMD was both anamnestically and clinically assessed, independently by different examiners. A total of 21.5% of the Dutch adult population reported dysfunction, but 85% of these perceived no need for treatment. With most of the remaining 15% either seeking or intending to seek treatment (or having had it before), a figure of 3.1% can be used to summarize the actual level of treatment need for CMD in the Dutch adult population. PMID- 1522295 TI - A semi-empirical model for prediction of how post-retained crowns will fail under compressive loading. AB - The aim of this in vitro study was to determine the relative contributions to retention of the different components of the post-retained crown and the mode of failure when the crown was loaded at 50 degrees to the vertical (i.e., in an apical direction). Failure was initiated in all the specimens as a rotation of the crown about a point on the labial surface of the root at the crown-root interface with pull-out of the post. A semi-empirical model was developed to explain this mode of failure. From experimental results, it was noted that the retention provided by the post was the most significant factor in the equation. However, large variation in the maximum forces recorded from pull-out tests on 40 posts suggested that the glass-ionomer cement was acting in the manner of a brittle composite material whose failure may be attributed to defects in the structure causing stress concentrations. The probability of survival at each ultimate strength recorded experimentally was plotted for comparison with the curve generated by the derived Weibull function. Close agreement was noted. Thus, for any given force applied compressively at 50 degrees to the vertical to a post retained crown of known dimensions, it is possible, by use of the described equation, to calculate the force, P, applied to the post. This value of P may then be inserted into the Weibull equation to give the probability of the crown failing under that applied force. PMID- 1522296 TI - The dependence of shrinkage stress reduction on porosity concentration in thin resin layers. AB - The development of polymerization contraction stress was determined as a function of the surface area of porosity, so that the contribution of voids in resin composite to stress relief could be investigated. Experiments were carried out on 200-microns-thick layers of resin bonded from wall to wall in a restrained condition. The resin samples were divided into three groups: Group A was without porosity, group B contained a small number of pores, and group C contained a large number of pores in comparison with group B. For each group, porosity area, maximal stress, and stress development rate were determined. The mean maximal stress and stress development rate were inversely proportional to the mean porosity surface. These characteristics differed significantly (p less than 0.01) between group A and C. For determination of whether shrinkage stress reduction has to be ascribed to flow from the outer surfaces of the voids or to inhibition of the setting reaction by oxygen in the voids, resin containing only nitrogen bubbles was also tested. The results indicated that both aspects contributed substantially to shrinkage stress relief. Incorporation of pores by the stirring of a luting cement contributes to stress reduction and can therefore be considered as a contribution to the maintenance of marginal integrity. PMID- 1522297 TI - Influence of tempering method on residual stress in dental porcelain. AB - The porcelain component of a porcelain-fused-to-metal restoration is strengthened by residual (tempering) stresses which are induced by cooling procedures followed in dental laboratories. The thermophysical properties of materials and cooling rate are the main factors which determine the residual stress. In this paper, the temperatures in the midplane of body-porcelain disks were measured from a heat soak temperature (1000 degrees C) to room temperature during two different cooling procedures: slow cooling in air and forced-air cooling. Experimental results approximated exponential cooling wherein the cooling rates could be represented by a linear equation of temperature. Residual stresses, as affected by the tempering method and thickness of a porcelain disk, were calculated by computer simulation for regions away from the edges. The following temperature dependent factors were incorporated into the simulation: elastic modulus, viscosity, and coefficient of thermal expansion. The cooling rate dependencies of the glass transition temperature and the temperature distribution during cooling were also included. The cooling rates used in this simulation were derived from the tempering data. The agreement between development of transient and residual stresses--calculated by computer simulation for various cooling methods, and the tendency toward failures of porcelain disks subjected to the tempering processes- was examined. Simulated residual stresses were also in good agreement with those measured by the indentation fracture method of Marshall and Lawn (1977) and Anusavice et al. (1989). PMID- 1522299 TI - What's in those wonder(ful) restorative materials? PMID- 1522298 TI - Early bond strength of luting cements to a precious alloy. AB - Previous studies have reported that glass-ionomer and adhesive resin cements can bond to various alloys, while zinc phosphate cements lack this adhesive property. This study evaluated the bonding properties of three luting cements during the first seven days after cementation. Thirty cylinders were cast with a high-noble porcelain-fused-to-metal (PFM) alloy and luted in pairs with one of the cements. The joints were stored in water at 37 degrees C for one, two, or seven days before being fractured in shear. The cylinders were re-used to provide 40 joints within each test group. The data were subjected to a Weibull analysis, a curve fitting method shown to be appropriate for comparing the bond strengths of dental materials. The results showed that the zinc phosphate cement was the weakest material, whereas the adhesive resin produced the strongest joints. Microscopic observations of the fractured samples did not reveal any specific differences between the samples in terms of their mechanism of fracture. The glass-ionomer cement reached its maximum bond strength after two days, whereas storage time had no influence on the zinc phosphate cement. The adhesive resin cement was slightly, but not significantly, weaker after one week in water. We suggest that excessive loading of restorations cemented with glass ionomer should be avoided for the first two days after the placement. The use of an adhesive resin cement can be recommended on endodontically treated teeth, but further studies are needed to evaluate its biocompatibility and adhesion to dentin. PMID- 1522300 TI - Febrile convulsions: concepts and management. PMID- 1522301 TI - AIDS and blood transfusion. PMID- 1522302 TI - Epidemiology of snake bite in the district of Burdwan, West Bengal. AB - An epidemiological field survey on snake bite was conducted on 26 randomly selected villages with a population of 18,892 in the district of Burdwan, West Bengal to assess the magnitude of the problem in a decade (1980-1989). Total number of snake bite, number of presumably poisonous snake bite and deaths due to snake bite poisoning were 307, 48 and 31 respectively. The death rate among snake bite victims was 10.09%. Males (54.72%) were bitten more than females (45.23%) and highest incidence of snake bite was found in the age group of 21-30 years and during the months of July and August. Majority of the snake bites (53%) were encountered in the lower extremities. Among the snake bite patients 201 (65.47% went to the traditional healers (ozhas) and 68 (22.14%) persons received hospital treatment, while 12 (3.09%) people neither went to the ozhas nor to hospital and 26 (8.46%) persons went to hospital after consulting the ozhas. If the present data are extrapolated for the total population of the district, average number of snake bite and death per year would be 7,857 (0.16%) and 793 (0.016%) respectively. Deaths due to snake bite per 100,000 population varied from 5.28 to 31.75 (average 16.4) over 10 years. PMID- 1522303 TI - A perforated appendix: should we drain? AB - The effectiveness of intraperitoneal drain was studied on patients undergoing appendicectomy for perforated appendicitis. Randomly 40 patients were allocated with drainage by corrugated rubber drains and 46 patients were without drainage. There were 5 deaths in the series, out of which 4 (10%) were in the drainage group and one (2.2%) in the group without drainage. The incidences of major wound sepsis, paralytic ileus, intraperitoneal abscess and urinary infection were observed in 55%, 42.5%, 12.5% and 15% respectively in drainage group and 50%, 28.3%, 21.7% and 15.2% respectively in non-drainage group. Occurrence of subphrenic abscess (7.5%), burst abdomen (5%) and faecal fistula (5%) were confined to drainage group only. PMID- 1522304 TI - A study of caesarean section cases with special reference to maternal and neonatal outcome. AB - Two hundred cases of lower uterine segment caesarean section were studied in SSKM Hospital and IPGME&R, Calcutta (a referral hospital) during the period 1986-1987. All were unselected cases of which 192 were booked and 8 were unbooked. The maximum number of caesarean sections were done in the age group of 21-30 years ie, in 154 cases (77.00%). Of total number of cases 53.5% were primigravida, and rest were multipara. Postoperative complications were noted in 42 cases (21%). Complications were more in unbooked and emergency cases ie, 7 (87.5%) and also in cases of antepartum haemorrhage (3 out of 8 cases) and where foetal distress (12 out of 51 cases) ie, prolonged labour, difficult labour was present. Neonatal mortality and morbidity (8 and 26 out of 154 total births respectively) were high in the age group of 21-30 years. Neonatal complications following caesarean section were found in 21.8% patients in emergency caesarean section and 15.5% in elective caesarean section. Neonatal morbidity was 15% and perinatal mortality was 4% in this study. Asphyxia (11 cases) and respiratory distress syndrome (10 cases) were more dangerous complications in caesarean section. There was no maternal mortality in this series. PMID- 1522305 TI - Role of sublingual administration of tablet buprenorphine hydrochloride on relief of labour pain. AB - Tablet buprenorphine hydrochloride when administered to 34 primigravida women sublingually in a dose of 6 micrograms/kg body weight during the first stage of labour, the analgesic action started 30 minutes after administration of drug and the analgesic action increased gradually and reached its peak level 3 hours after administration of drug. Analgesic action continued throughout the first stage of labour when the duration after administration of drug was 9 hours. In one case maximum analgesic action did not persist after 9 hours. The average time of delivery was 5.88 hours having cervical dilatation of 3.1 (+/- 0.13) cm and the progress of labour was not delayed by the drug. There was no cardiorespiratory depression of the subjects. None complained of nausea or vomiting. There was no change in foetal heart rate and Apgar scoring of neonates revealed the average value of 9.71 at 1 minute and 9.94 at 5 minutes. PMID- 1522306 TI - Management of oral cancer in late stages: a review. AB - Sixty cases of oral cancer (2 were of stage II and other 58 were of stage III and stage IV) were treated and observed over a period of 2 years. In patients of oral cancer with bone involvement and mobile cervical nodes (44 cases) local excision which included partial or hemimandibulectomy with radical neck node dissection was performed. Out of these 44 cases, 18 cases received radiotherapy pre operatively and 26 cases postoperatively. Better results were observed in these cases. When the growth was inaccessible and/or nodes were fixed (13 cases) radiotherapy was found to be suitable. Fistula formation and reconstructive flap necrosis were common following surgery after radiotherapy. Combined modalities of treatment with pre- and postoperative radiotherapy and radical neck node dissection showed excellent results (86.4%) in majority of cases. The remaining one patient received chemotherapy and local excision was performed in 2 cases. PMID- 1522307 TI - Diphtheria in the eighties: experience in a south Indian district hospital. AB - Epidemiological and clinical analysis of 228 cases of diphtheria treated during a 10-year period from 1980-1989 is presented. No statistically significant change in the incidence over a decade was noticed. A high percentage of cases (44.74%) were noted in the age group of 5 years and above. Bilateral tonsillar and pharyngeal membranes together were seen in 60% cases. All patients were treated with diphtheria antitoxin and benzyl penicillin. Severe myocarditis (9 cases), fulminant haemorrhagic complications (2 cases), palatal palsies (11 cases) and polyneuritis and cranial nerve paralysis (2 cases) were the significant complications. Case fatality rate was 13.21%. Statistically significant increase in the mortality (p less than 0.05) was noticed in the year 1987 and onwards. In this period, myocarditis (8 out of 16 deaths) is gradually replacing laryngeal obstruction, the major cause of death in early eighties or post-tracheostomy complications (6 out of 16 deaths). Only 2 patients died of haemorrhagic diphtheria in this period. PMID- 1522308 TI - Paediatric colonic silicobezoars. PMID- 1522309 TI - Retroperitoneal Burkitt's lymphoma. PMID- 1522310 TI - Calyceal diverticula. PMID- 1522311 TI - Occipital lobe infarction caused by tentorial herniation. PMID- 1522312 TI - Latest income-tax amendments for doctors. PMID- 1522313 TI - Hypervitaminoses. PMID- 1522314 TI - Use of antiprotozoan and anthelmintic drugs during pregnancy: side-effects and contra-indications. PMID- 1522315 TI - Fatal varicella hepatitis in a patient with AIDS. PMID- 1522316 TI - Gemella morbillorum endocarditis in an intravenous drug abuser. PMID- 1522317 TI - Capnocytophaga canimorus infection and acute renal failure. PMID- 1522318 TI - Group G beta-haemolytic streptococcal vertebral osteomyelitis. PMID- 1522319 TI - Staphylococcus lugdunensis endocarditis. PMID- 1522320 TI - Single-dose ciprofloxacin for shigellosis in adults. PMID- 1522321 TI - Antimicrobial chemotherapy of meningitis due to Listeria monocytogenes in adults. PMID- 1522322 TI - An evaluation of inpatient consultations conducted by clinical microbiologists in a teaching hospital. AB - A systematic procedure for conducting consultations by clinical microbiologists requested by their clinical colleagues is described. The method was evaluated over a period of 17 months and involved sequential consultations related to 229 patients with known or probable infections. An attempt was made to elucidate the contributions of the clinical microbiologists in achieving a better understanding of the problems experienced in this particular setting and which in turn led to improved management of patients. It is hoped that this paper may provide a practical working framework for clinical microbiologists in the care of patients suffering from infection. PMID- 1522323 TI - Urinary-tract infections in African neonates. AB - During a 4-year period between January 1987 and December 1990, 41 high-risk neonates with proven urinary tract infections (UTIs) were studied prospectively and compared with 55 control neonates. An incidence of 2.6 UTIs per 1000 live births was noted, amongst whom no obvious radiological abnormalities of the urinary tract were found. Significantly, more males than females developed UTIs, the ratio being 4.5:I. Low-birth-weight babies were significantly more often affected than those of normal weight (P less than 0.05). Staphylococcus aureus and Klebsiella spp. were the predominant pathogens isolated. Aetiologically, bacteraemia from sepsis was important. Most of the infants presented with a significantly higher incidence of pyrexia, abdominal distension, lethargy and jaundice (P less than 0.01). The overall mortality rate of 17.1% was closely related to these associated problems. The relatively high incidence of UTI and the rarity of radiological abnormalities of the urinary tract in the African neonate contrast with previous reports in the literature and the reason is worthy of consideration. Despite the rarity of urinary-tract anomalies, a continuous surveillance of the trend of neonatal UTI and its outcome is recommended. PMID- 1522324 TI - Experience with Vi typhoid capsular polysaccharide vaccine in the U.K. AB - Adult volunteers were immunised with a single dose of typhoid Vi capsular polysaccharide vaccine. After immunisation, 96% of the 103 subjects seroconverted and 94% had antibody levels above the protective threshold. Systemic reactions were uncommon, local reactions were mild and transient. PMID- 1522325 TI - Pneumonia due to Legionella bozemanii and Chlamydia psittaci/TWAR following renal transplantation. AB - Chlamydia and Legionella are recognized causes of atypical pneumonia. A case of pneumonia due to Chlamydia psittaci/TWAR and Legionella bozemanii following renal transplantation is described. Legionella bozemanii infection was diagnosed by a rise in antibodies and by isolation of the organism from bronchoscopy specimens. It is unusual to find pneumonia caused concomitantly by two such agents. This case, despite the fatal outcome, emphasises the necessity for a comprehensive approach to the diagnosis of atypical pneumonia, including culture for Legionella, especially in immunocompromised patients. PMID- 1522326 TI - Acremonium infection in a neutropenic patient. AB - Acremonium species (previously Cephalosporium) are saprophytic moulds of low pathogenicity commonly found in the environment. We report a case of repeated acremonium fungaemia in a neutropenic patient, probably associated with a Hickman line. Fungaemia was accompanied by fever and a papular skin rash, both of which appeared to resolve when the neutrophil count recovered without antifungal chemotherapy, only to return when the patient next became neutropenic. PMID- 1522327 TI - Prosthetic hip-joint infection associated with a penicillin-tolerant group B streptococcus. AB - We report a case of prosthetic hip-joint infection with Streptococcus agalactiae (Lancefield group B streptococcus). The infection recurred after 3 months' treatment with amoxycillin. On further investigation, the isolate was found to be amoxycillin-tolerant. Addition of gentamicin abolished tolerance in vitro and the patient has remained asymptomatic since receiving a 10-day course of amoxycillin and gentamicin followed by amoxycillin alone. PMID- 1522328 TI - Pericarditis, pneumonia and brain abscess due to a combined Actinomyces- Actinobacillus actinomycetemcomitans infection. AB - A patient is described in whom there developed a pulmonary infiltrate and constrictive pericarditis caused by a combined Actinomyces and Actinobacillus actinomycetemcomitans infection, presumably originating from his poor dentition. The diagnosis was only made following repeated thoracotomy. After surgery, long term treatment with antibiotics led to complete clinical recovery. None the less, some months later he was found to have a brain abscess which resolved during a further course of antibiotics. The variable clinical picture of actinomycosis is discussed, as well as the role of other bacteria frequently associated with actinomycotic infection, in particular Actinobacillus actinomycetemcomitans. The therapeutic implications are described. PMID- 1522329 TI - Titres of class-specific antibodies against Shigella and Salmonella lipopolysaccharide antigens in colostrum and breast milk of Costa Rican, Swedish and Vietnamese mothers. AB - Enzyme immunoassays (EIA) were used to estimate titres of class-specific antibodies against purified and chemically defined phenol-water-extracted lipopolysaccharide (LPS) antigens of Salmonella serogroup B (BO), Shigella dysenteriae type I, Plesiomonas shigelloides (the same O-antigen as Shigella sonnei) and Shigella flexneri Y. Titres in colostrum and breast milk of Swedish, Vietnamese and Costa Rican mothers from various socioeconomic conditions were compared. The antibodies were mainly of the IgA isotype. IgM antibodies were also present, but only very low concentrations of IgG were found. In Costa Rican mothers, the IgA antibody titres were significantly higher (P less than 0.05) in women of low and middle socioeconomical conditions than were those in mothers of high socioeconomical level. The low titres in the last group were comparable to those found in Swedish mothers. The IgA antibody titres found in Vietnamese mothers were similar to those of Costa Rican mothers from the low and middle socioeconomic conditions, being highest against S. flexneri Y LPS. The IgM antibody titres were also highest in Vietnamese mothers, immediately followed by the Costa Rican mothers of low socioeconomic conditions. The low IgM titres in the Costa Rican women of high socioeconomic level were comparable to those seen in Swedish mothers. The results suggest that, in Costa Rica and Vietnam, S. flexneri is the most prevalent Shigella sp. causing infection and that Salmonella serogroup B infections are rare in all three countries. The results also show that the antibody repertoire in colostrum and breast milk varies. Furthermore, in addition to the prevalence of a specific micro-organism in a determined geographical area, such differences may be associated mainly with exposure to certain pathogens in particular socioeconomic conditions. PMID- 1522330 TI - The molecular biology of chlamydia--a brief overview. PMID- 1522331 TI - BSSI: Chlamydia Supplement 1992. PMID- 1522332 TI - Ovine chlamydiosis in an abattoir worker. AB - The strain of Chlamydia psittaci causing enzootic abortion in ewes (the EAE strain) may cause serious infection in pregnant women, often resulting in hepatic and renal dysfunction, disseminated intravascular coagulation and fetal loss. The first case of such an infection in an abattoir worker is described and the possibility of human-to-human transmission considered. Direct handling of sheep or their products of conception can usually be established but this is not always so. There is much still to be learned about this uncommon but severe zoonosis. PMID- 1522333 TI - Chlamydial vaccines--future trends. PMID- 1522334 TI - Coxiella burneti endocarditis in a patient with positive chlamydial serology. AB - A 41-year-old man who habitually slept in a car park presented with a culture negative endocarditis. Serological tests indicated infection with both Coxiella burneti and Chlamydia psittaci. He was treated with doxycycline and clindamycin and required aortic valve replacement. Culture of the excised value for both agents was negative but electron microscopy was suggestive of coxiella endocarditis. PMID- 1522335 TI - The epidemiology and significance of Chlamydia pneumoniae. AB - Chlamydia pneumoniae has recently been found to be a new chlamydial species transmitted directly from man to man, obviously through the respiratory tract. It is the commonest chlamydia of mankind but fortunately the overwhelming majority of infections are mild, it has been estimated that 10% of all pneumonias are caused by this species. Since the most important chlamydial infections are chronic in nature, the question of possible chronic C. pneumoniae infections is of paramount importance. Apart from being associated with chronic inflammatory processes of the respiratory system, a quite unexpected connection to coronary heart disease has now been suggested. PMID- 1522336 TI - Male genital Chlamydia trachomatis infections. AB - The role of Chlamydia trachomatis in infections of the male genital tract is reviewed. The organism is an important cause of non-gonococcal urethritis, post gonococcal urethritis and epididymitis, but does not appear to play a major part in the pathogenesis of chronic abacterial prostatitis or in proctitis in anoreceptive homosexual men. PMID- 1522337 TI - Genital Chlamydia trachomatis infections in the female. PMID- 1522338 TI - Extra-genital Chlamydia trachomatis infection as sexually-acquired reactive arthritis. PMID- 1522339 TI - Advances in the antimicrobial therapy of chlamydial genital infections. PMID- 1522340 TI - Laboratory methods for chlamydial infections. PMID- 1522341 TI - The laboratory diagnosis of male Chlamydia trachomatis infections--a time for change? AB - We carried out a two-phased study comparing the effectiveness of first-catch early morning urine (FCU) samples against urethral swabs for the detection of C. trachomatis in men. Four hundred and seventeen new and re-booked consecutive men, who attended the Department of Genito-Urinary Medicine, Bristol, having held their urine overnight, were recruited. Patients who had received antimicrobial chemotherapy in the preceding 2 months were excluded. Early morning FCU samples were obtained from 208 men followed by urethral swabs for the detection of C. trachomatis (phase I) and this order of collection was reversed for the remaining 209 patients (phase 2). A last-catch urine (LCU) was also obtained from all patients. All urethral and urine samples were examined by an amplified enzyme immunoassay (IDEIA, Dako Diagnostics Ltd). Initially, discordant samples were critically examined by direct immunofluorescence (Syva, 'Microtrak') which was used as the 'gold' standard in this study. We have shown that overall 42 and 4.7% of our symptomatic and asymptomatic male patients respectively were positive for C. trachomatis antigen by IDEIA. Furthermore 86.4 and 91.0% (phases 1 and 2) of the total C. trachomatis positive samples were detected by examination of an FCU sample. In contrast only 66.0 and 65.5% (phases 1 and 2) of the total positives were identified by examination of an urethral swab. These results show that an FCU sample not only has the advantage of being a non-invasive procedure but is also a very sensitive method, compared to swabbing the urethra for the detection of C. trachomatis.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1522342 TI - The differentiation of Chlamydia species by antigen detection in sputum specimens from patients with community-acquired acute respiratory infections. AB - An amplified enzyme immunoassay (IDEIA III: Dako Diagnostics Ltd) for detecting genus-specific chlamydia antigen was evaluated prospectively on 286 respiratory specimens from 275 patients presenting with community-acquired pneumonia or persistent chest infection. Nineteen patients had evidence of recent chlamydial infection, having two or more positive sputum or serological markers. Sputa from two other patients were ELISA-positive in the absence of other positive criteria and were regarded as false-positive results. When compared with a direct immunofluorescence test for chlamydial elementary bodies (EBs) using a genus specific monoclonal antibody, the ELISA gave a positive predictive value of 91% and a negative predictive value of 99%. Non-specific problems with a wide variety of other micro-organisms isolated from the sputa were not encountered. Attempts to differentiate between Chlamydia psittaci, Chlamydia pneumoniae and Chlamydia trachomatis using genus-specific lipopolysaccharide reactive--and species specific major outer membrane protein--monoclonal antibodies were encouraging and results were substantiated, in most patients, by the species-specific serological assays of the whole-cell-inclusion immunofluorescence or micro-immunofluorescence assays. The study demonstrated that antigen detection techniques offer scope for routine laboratories to diagnose chlamydial respiratory infections rapidly and reliably and may enable differentiation to species level. Although immunofluorescence offers marginally greater sensitivity and specificity when compared with ELISA, the latter is less subjective and less demanding. Sixty eight per cent of these infections would have remained undiagnosed despite the general availability of ELISA tests. PMID- 1522343 TI - Prevalence of antibodies to Chlamydia pneumoniae in a Belgian population. AB - To evaluate the prevalence of antibodies to Chlamydia pneumoniae in a healthy adult Belgian population a study group of 150 medical students was chosen. Sera were collected in the period between March and October 1990 and assessed by the microimmunofluorescence test. Sixty-one per cent were found to have IgG antibodies to C. pneumoniae in a titre greater than or equal to 16, which showed evidence of past infection. Twenty-one per cent had IgA in a titre greater than or equal to 8. In none were antibodies of the IgM fraction detected. The same sera were tested for the presence of antibodies to Chlamydia trachomatis. One hundred and thirty-one sera with no or low titres of antibodies to C. pneumoniae tended to have low or no detectable antibodies to C. trachomatis. Nineteen sera with high (greater than 128) titres of antibodies to C. pneumoniae had IgG antibodies in a titre of greater than or equal to 32 to C. trachomatis. This prevalence (13%) is much higher than one would expect in a population at low risk for C. trachomatis infection. The problem of possible cross-reactions between the three species in the micro-immunofluorescence test is discussed. PMID- 1522344 TI - A comparison of the seroepidemiology of chlamydial infection in pigeon fanciers and farmers in the U.K. AB - A detailed comparative seroepidemiological study of antibody responses was performed in 271 pigeon fanciers and 100 farmers. Overall 73% of pigeon fanciers had IgG antibodies at a titre greater than or equal to 16 to Chlamydia pneumoniae, 39% to Chlamydia psittaci, and 6.6% to Chlamydia trachomatis. The prevalence of chlamydial antibodies was significantly lower in the farmers at 47% for C. pneumoniae, 6% for C. psittaci, and 2% for C. trachomatis. Both populations were exposed to complex microbiological and antigenic environments: 50.5% of the pigeon fanciers had antibodies to pigeon antigens, 34% to egg membrane, and 0.73% to yolk sac antigen, and 59% of the farmers had antibodies to Micropolyspora faeni, but the high prevalence of chlamydial antibodies could not be attributed to interaction with these antigens. There was considerable overlap of chlamydial antibody responses in the pigeon fanciers but not in the farmers: 36% of the pigeon fanciers had antibodies to C. pneumoniae alone, 5% to C. psittaci alone, and 31% to both agents, whereas only 3% of farmers had antibodies to both C. pneumoniae and C. psittaci. The high prevalence of antibodies to C. psittaci in the pigeon fanciers is compatible with the known avian reservoir for this infection. The particularly high prevalence of antibodies to C. pneumoniae suggests that complex interactions may be occurring in a population exposed to two chlamydial organisms, whereby infection with one species may provoke an anamnestic response against other chlamydial organisms with which the subject has previously been infected. PMID- 1522345 TI - A family outbreak of Chlamydia pneumoniae infection. AB - Chlamydia pneumoniae, a newly described Chlamydia species, has been shown to be a cause of acute respiratory tract infection in both adults and children, but its role in human infection is still under investigation. Here we present a family outbreak of C. pneumoniae infection where three members of a family presented with a 'flu-like illness' and acute upper respiratory tract infection which did not improve despite penicillin or septrin therapy. No history of exposure to birds, pets or animals was obtained. As C. pneumoniae isolation from respiratory secretions is not without difficulty, diagnosis usually relies currently on serum based tests. In this study C. pneumoniae specific IgM determined by the micro immunofluorescence test was detected in the three clinical cases. All three cases had an elevated complement-fixing antibody titre to Psittacosis-LGV antigen, which may have suggested psittacosis, if type-specific tests had not been performed. In addition, three other members of the family had C. pneumoniae specific IgG antibody although specific IgM was absent. These three younger members of the family had been symptomatic in the month preceding symptoms in their older sibling and their parents. All the symptomatic members of the family made a complete recovery on tetracycline therapy. PMID- 1522346 TI - [Ribosomal RNA synthesis in the nucleolus]. PMID- 1522347 TI - [Regulatory mechanism in animal mitochondrial DNA transcription]. PMID- 1522348 TI - [Improved protocols for DNA sequencing with chemiluminescence]. PMID- 1522349 TI - Vascular Medicine at Mayo Clinic. Some highlights of the early history and development as a subspecialty. PMID- 1522350 TI - Functional changes in canine saphenous veins after cryopreservation. AB - This study was designed to determine the functional characteristics of the endothelium, smooth muscle and nerve terminals of cryopreserved veins. Freshly harvested and cryopreserved canine saphenous veins were cut into rings. In some rings, the endothelium was removed. Cryopreserved veins were stored at -196 degrees C for at least 3 weeks prior to use. All rings contracted in a concentration-dependent manner to depolarization with KCl and to alpha-adrenergic stimulation; the maximal tensions were significantly less in cryopreserved than in freshly harvested veins. Calcium ionophore A23187 caused greater relaxations in rings with than without endothelium in freshly harvested and cryopreserved veins. These relaxations were reduced significantly by methylene blue and NG monomethyl-L-arginine (L-NMMA) only in fresh veins. Cocaine-sensitive uptake of H3-norepinephrine was reduced following cryopreservation. Immediately after cryopreservation, the production of prostacyclin was elevated. The calcium ionophore A23187 stimulated production of prostacyclin only in freshly harvested veins. Tissue content of endothelin did not change following cryopreservation. These results suggest that cryopreservation of canine saphenous veins alters nerve terminals and decreases the ability of the smooth muscle to contract. The endothelium releases an endothelium-derived relaxing factor and prostanoids following cryopreservation but the ability to synthesize nitric oxide is probably reduced. These changes following cryopreservation may affect patency of the veins when used as arterial grafts. PMID- 1522351 TI - The use of transcutaneous oximetry in the noninvasive vascular laboratory. AB - Transcutaneous oximetry is gaining worldwide acceptance as a simple and effective means of evaluating the cutaneous circulation. Oximetry involves the use of Clark type electrically heated oxygen-sensing electrodes that are attached to the skin; various protocols for the performance of studies (utilizing exercise, oxygen inhalation, leg elevation, and various other maneuvers) have been developed which may improve the accuracy when used in certain settings. Applications for transcutaneous oximetry are found in areas such as: (1) diagnosis of disease, (2) quantification of disease severity, (3) prediction of healing potential for skin ulcers or amputation sites, (4) assessment of microvascular disease, and (5) determination of cutaneous vasomotor status. Transcutaneous oxygen tension serves as an index of the adequacy of skin blood flow, and therefore yields valuable "functional" information not provided by noninvasive "anatomical" testing modalities such as echo-doppler ultrasound imaging. PMID- 1522352 TI - Chronic pernio: another cause of blue toes. AB - It is the purpose of this report to focus attention on the clinical features, diagnosis, and management of chronic pernio. Thirty-nine patients meeting our strict criteria for a diagnosis of chronic pernio were seen at the Mayo Clinic between 1976 and 1988 and form the basis for this report. Persons with upper extremity lesions only were excluded. Twenty-eight of the patients were female, 11 were male. Age at onset of symptoms ranged from 13 to 68 years of age, with symptoms appearing from 1 to 37 years following cold injury. The lesions were bilateral in 35 (90%) of patients and symmetric in 28 (71%). Nine patients who underwent skin temperature studies following cold water immersion, showed a vasospastic response. Chronic pernio is characterized by recurring erythematous, vesicular or ulcerative lesions of the lower extremities and toes, but may present with only digital cyanosis, usually bilateral and commonly symmetrical. The diagnosis is suggested by eliciting a temporal relation between cool weather and symptom onset, particularly if there is no associated occlusive peripheral arterial disease. Treatment consists of avoidance of cold and other vasoconstrictive influences. Prazosin has been effective in the acute management and as prophylaxis against recurrences. PMID- 1522353 TI - The prevalence of vascular occlusive disease associated with antiphospholipid syndromes. AB - The association of anticardiolipin antibodies (aCL) with unexplained vascular occlusive disease (VOD) is well known. We reviewed the records of 102 consecutive patients seen over a 9 months period who had positive IgG or IgM aCL to determine the frequency and types of VOD in this unselected group of patients. Lupus anticoagulant was detectable in 17 of 67 (25%) patients tested. VOD occurred in 80 of 102 (78%) aCL-positive patients comprised of 17 (16.7%) with systemic venous VOD or pulmonary embolism; 27 (26.5%) with cerebral VOD: 11 (10.8%) with systemic arterial VOD; 3 (2.9%) with coronary thrombosis; and 5 (4.9%) with visceral venous or arterial VOD. Of the 19 obstetric patients with positive aCL, 17 (89%) had at least one unexplained fetal loss and 8 of the 17 (47%) had multiple or recurrent fetal losses. Twelve (11.7%) of the 102 patients met the ACR criteria for systemic lupus erythematosus (SLE). Additionally, 12 (11.7%) patients were identified as nonSLE or undifferentiated connective tissue disease (CTD). The remaining 78 (76%) had no known underlying disease (primary antiphospholipid syndrome). We conclude that IgG and IgM aCL with or without lupus anticoagulant are associated with diverse types of VOD but cerebral VOD appears predominant. aCL-associated unexplained VOD occurs frequently in patients without evidence of CTD-65 of 80 (81%) in our series. Testing for aCL is essential for identifying patients with unexplained VOD, and it should be performed in prospective clinical studies of such patients to better define the pathogenic role of aCL in the natural history of unexplained VOD. PMID- 1522354 TI - An analysis of current pulmonary embolism therapy. AB - The clinical diagnosis of venous thromboembolism, and especially pulmonary embolism, is inaccurate due to the nonspecific nature of presenting symptoms and signs which overlap with other frequently coexistent conditions. In recent years, the operating characteristics of more objective diagnostic strategies (ie, ventilation/perfusion lung scan, impedance plethysmography, venous compression ultrasound) have been more clearly defined. However, data regarding the natural history of pulmonary embolism primarily come from an era when objective diagnostic tests were unavailable which calls into question the validity of such data. Furthermore, despite a long experience there are few data regarding the clinical course of pulmonary embolism as currently treated with heparin/warfarin anticoagulation. Acute mortality correlates with the presence of systemic hypotension regardless of embolus size, suggesting that right heart functional reserve is the major determinant of acute survival. Long-term mortality has been attributed to underlying co-morbid disease. However, there are no studies of age- and sex-specific survival which control for co-morbid disease. Pulmonary embolism may be a marker for severe and imminently fatal co-morbid disease, or pulmonary embolism may add "excess mortality" over and above that co-morbid disease. Thrombolytic therapy clears pulmonary artery thrombus more rapidly than heparin and can rapidly restore normal right heart function. Current research aims to identify the ideal plasminogen activator and dosing regimen which maximizes thrombolysis and minimizes disturbance of hemostasis. In addition, more data regarding the natural history and clinical course of pulmonary embolism is needed to stratify patients into subsets with better or worse prognosis.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1522355 TI - The current role of surgical revascularization for combined renovascular hypertension and renal insufficiency. AB - The number of elderly patients presenting with the difficult combination of renovascular hypertension and deteriorating renal function is increasing. The majority of these patients have diffuse cardiovascular disease requiring careful preoperative evaluation and stabilization. Adequate control of hypertension and preservation of renal function frequently requires bilateral renal procedures in addition to aortic replacement in patients with significant aorto-iliac disease or aortic aneurysms. Early and late results continue to justify prompt surgical consultation and revascularization of patients with combined renovascular hypertension and renal insufficiency. PMID- 1522356 TI - The evolving knowledge of the physiopathology of the circulation in human limbs. From sympathectomy to molecular biology. PMID- 1522357 TI - Accelerated atherosclerosis, aneurysmal disease, and aortitis: possible pathogenetic association with cocaine abuse. AB - Cocaine abuse and its association with vascular disease has become common in the medical literature. A variety of vascular problems have been described including neurovascular complications, cardiovascular complications, aortic dissection, venous thrombosis, mesenteric artery thrombosis, and renal infarction. The pathogenesis of these vascular complications has largely been related to increased adrenergic activity leading to vasospasm. Interaction of cocaine with the vascular endothelium resulting in thrombosis or vasculitis has also been suggested. We report a case of diffuse aneurysmal change of the aorta associated with an atypical inflammatory component consistent with possible cocaine induced vasculitis. PMID- 1522358 TI - Relapses in leprosy patients after release from dapsone monotherapy; experience in the leprosy control program of the all Africa Leprosy and Rehabilitation Training Center (ALERT) in Ethiopia. AB - Before implementation of multidrug therapy (MDT), leprosy patients who were clinically inactive, skin-smear negative and had been treated with dapsone monotherapy for at least 5 years (paucibacillary patients) or for at least 10 years (multibacillary patients) were released from treatment. An analysis was made of self-reporting relapses in 1081 paucibacillary (PB) patients and 1123 multibacillary (MB) patients who had been released in Addis Ababa and two rural districts of the leprosy control program of the All Africa Leprosy and Rehabilitation Training Center (ALERT). During an average period of 6.6 years after stopping dapsone, 44 relapses were diagnosed among the PB patients and 148 relapses among the MB patients. The overall relapse rate was 4.1% or 7.2 per 1000 patient-years after release from treatment for PB patients and 13.2% and 24.8, respectively, for MB patients. The annual relapse rate in PB patients did not differ significantly from year to year. However the relapse rate for MB patients was significantly lower during the fifth to seventh years after stopping treatment compared with the first 4 years. Based on clinical findings there was a strong suspicion of relapse with dapsone-resistant bacilli in 40.4% of MB relapses. It is concluded that the relapse rate for PB patients is acceptable. However, the relapse rate for MB patients is considered too high. It is strongly recommended to administer to all MB patients, including those who have been on long-term treatment with dapsone and have become clinically and bacteriologically inactive, a 2-year course of MDT. PMID- 1522359 TI - Occurrence of reactions, their diagnosis and management in leprosy patients treated with multidrug therapy; experience in the leprosy control program of the All Africa Leprosy and Rehabilitation Training Center (ALERT) in Ethiopia. AB - This paper reports on reactions in leprosy patients who were treated with multidrug therapy (MDT) in the leprosy control program of the All Africa Leprosy and Rehabilitation Training Center (ALERT) in Ethiopia. Only those reactions which occurred in patients who had not been treated with dapsone before MDT and which required treatment with prednisolone were included. Until the end of the second year of MDT a reversal reaction had been diagnosed in 43.6% of 266 borderline lepromatous (BL) patients and in 19.2% of 109 lepromatous leprosy (LL) patients, and an erythema nodosum leprosum (ENL) reaction in 2.7% and 11.1% of the patients, respectively. The reversal reactions were observed in 4.9% of the BL patients and in 0% of the LL patients at the time of diagnosis of leprosy, in 26.3% and 12.8% of the patients during the first year of MDT, and in 12.4% and 6.4% during the second year of MDT. ENL reactions were seen in 0.8% of BL patients at diagnosis, 1.1% in the first year and 0.8% in the second year and 2.8% at diagnosis, 5.5% in the first year, and 2.8% in the second year for LL patients. During a 3 1/2-year period, a total of 405 reactions were diagnosed among multibacillary (MB) patients on MDT; 365 of these reactions (90.1%) were reversal reactions and only 40 (9.9%) were ENL reactions. The point in time of the reversal reactions showed that the risk of reversal reaction is highest during the first year of MDT. Thereafter there is a gradual decline, although reactions were still observed during the fifth year of MDT. A reversal reaction was diagnosed in 21.0% of 438 BT patients; in 3.4% of the patients the reaction was present at the time of diagnosis of leprosy; in 10.3% it occurred during MDT, and in 7.3% during the first year after release from MDT. During a period of 3 1/2 years a total of 183 reversal reactions were diagnosed among BT patients. The point in time showed a declining trend in the risk of reversal reaction after starting MDT. The risk is highest during MDT, followed by the first 6 months after stopping MDT. However, reactions, although few, still occurred during the fourth year after stopping MDT. The analysis of the results of prednisolone treatment in 161 patients who were treated for nerve function loss in the field showed that 142 patients (88.2%) regained complete or partial recovery of the nerve function(s), while no improvement was observed in 19 patients (11.8%).(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1522360 TI - Intravascular hemolysis and acute renal failure following intermittent rifampin therapy. AB - Renal failure is a rare complication associated with the use of rifampin. Intravascular hemolysis leading to acute renal failure following rifampin therapy is extremely rare. Two patients with leprosy who developed hemolysis and acute renal failure following rifampin are reported. PMID- 1522361 TI - Preliminary study of cellular immunity to Mycobacterium leprae protein in contacts and leprosy patients. AB - Because of the good results obtained in the mononuclear cell (T lymphocyte) proliferative response in tuberculoid leprosy patients and family contacts and healthy Mitsuda-positive volunteers using Mycobacterium leprae soluble extract, we prepared different protein fractions from the soluble extract. We used the T cell Western blot technique with separation by electrophoresis in SDS polyacrylamide gels and transfer onto nitrocellulose membranes. Each unstained blot was converted into 18 fractions of antigen-bearing particles and tested with peripheral blood mononuclear cells from 21 individuals including Mitsuda-positive contacts, vaccinated lepromatous leprosy (LL) patients, borderline tuberculoid (BT) patients, and unvaccinated lepromatous patients. The stimulation index (SI) of the contacts was higher to the different fractions in comparison with the leprosy patients. They showed four peaks of stimulation to fractions 66-55, 45 29, 22-18, and 14 kDa. The second highest responders were BT patients, followed by vaccinated LL patients. The unvaccinated patients did not respond significantly to any of the fractions (SI less than 1). PMID- 1522362 TI - Sero-immunoreactivity of cloned protein antigens of Mycobacterium leprae. AB - Sera from 173 leprosy patients with various types of disease (tuberculoid = TT, borderline tuberculoid = BT, borderline lepromatous = BL, and lepromatous = LL), 12 intrafamilial contacts, and 40 normal healthy individuals were assayed in an indirect enzyme-linked immunosorbent assay (ELISA) using Mycobacterium leprae antigens. Recombinant clones carrying M. leprae antigens, namely, Y3184 (12 kDa), Y3179 (18 kDa), Y3164 (28 kDa), Y3180 (36 kDa), and Y3178 (65 kDa) and a cell sonicate from armadillo-derived M. leprae were used for the study. A high degree of reactivity with the 65-kDa, 36-kDa, and 28-kDa protein lysates was observed in most of the sera from multibacillary patients, with a low degree of positivity with 18 kDa and 12 kDa. Only a few sera from paucibacillary patients showed positive reactions. The majority of the contacts' sera tested showed no reactivity with these antigens. PMID- 1522364 TI - Human phagocyte respiratory burst by Mycobacterium bovis BCG and M. leprae: functional activation by BCG is mediated by complement and its receptors on monocytes. AB - We have measured the role of serum components on two parameters of the phagocytosis reaction: a) the chemiluminescence (CL) response associated with the oxidative respiratory burst in response to Mycobacterium bovis BCG and M. leprae, and b) the uptake of these two mycobacteria by healthy human monocytes. Pre incubations of fresh or heat-inactivated serum or serum containing EGTA or EDTA indicate that these two mycobacteria activate the alternative complement pathway. Monoclonal antibodies against CR1 and CR3 inhibit the responses of M. bovis BCG and M. leprae, demonstrating that complement receptors mediate the phagocytosis of these two mycobacteria. Thus, complement and its receptors on the surface of the monocytes (CR1 and CR3) are important in the functional activation of phagocytosis of M. bovis BCG and M. leprae. PMID- 1522365 TI - Isolation of cultivable mycobacteria from feces and lungs of armadillos infected with Mycobacterium leprae. AB - In the past, no cultivable mycobacteria were isolated from armadillos captured in the state of Florida, U.S.A. But recent findings of acid-fast bacilli (AFB) in the lungs of armadillos infected with Mycobacterium leprae prompted us to undertake this study to determine the correlation between systemic leprosy infection and the occurrence of cultivable mycobacteria in the lungs and stools of these animals. No AFB could be isolated from noninfected animals. Seventy percent of the infected animals developed disseminated infection, but no cultivable mycobacteria were isolated from their livers and spleens. However, cultivable mycobacteria were isolated from the lungs and stools of a large number of armadillos showing disseminated infection. The most common among these were M. gordonae, M. fortuitum, and M. avium. There was a close correlation between the development of disseminated leprosy infection and the occurrence of cultivable mycobacteria in their lungs and stools, perhaps due to the decline in the immune system in these animals in the later stages of infection. PMID- 1522366 TI - Modulan grip-aids for leprosy patients. AB - Made-to-measure Modulan grip-aids were fitted to 755 articles for 155 patients with hand deformities due to leprosy. The acceptance of the grip-aids was, in general, good. No instance of contact dermatitis or skin irritation was reported. These grip-aids facilitated a normal grip with crippled hands, and thus considerably improved the quality of the patient's personal and working life. They increased the patient's self-esteem and self-confidence because he/she could handle everyday objects or tools without the help of others and could do his/her job--an important step toward social and economic rehabilitation. PMID- 1522363 TI - Relationships between titers of antibodies immunoreacting against glycolipid antigens from Mycobacterium leprae and M. tuberculosis, the Mitsuda and Mantoux reactions, and bacteriological loads: implications in the pathogenesis, epidemiology and serodiagnosis of leprosy and tuberculosis. AB - Analysis of cell-mediated immunity [(CMI) as judged from the Mantoux, Fernandez, and Mitsuda reactions and the presence of granulomas in biopsy material] against humoral immunity (measurements of anti-PGL-I, PGL-Tb1, and SL-IV IgG and IgM antibody titers by ELISA) were performed in selected human populations. The investigations yielded data indicating that humoral (B-cell) responses preceded protective CMI in both tuberculosis and leprosy. The B-cell responses were unrelated to (unfavorable) cell-mediated delayed-type hypersensitivity (DTH). Notwithstanding the difficulty in inferring sequential events from studies in humans, it was shown that in humoral responses there was an initial rise of specific IgM immunoglobulins that switched afterward to IgG production during subclinical tuberculosis and leprosy infections. In patent tuberculosis disease the IgM-to-IgG switch was observed in the majority of patients; in patent leprosy disease the switch was impaired in the majority of patients. The clinical, immunological, and laboratory data indicated that the B-cell responses were suppressed as protective CMI was re-established in the patients during the protracted subclinical infection. According to the data, the diagnosis of subclinical tuberculosis and leprosy may be accomplished using ELISA. The yearly risk of tuberculosis in apparently healthy persons but with significant antibody titers was estimated at 44%; the yearly risk for leprosy has not yet been established. The clinical, epidemiologic, and diagnostic implications of these findings are discussed. PMID- 1522367 TI - A quantitative basis for sustainable anti-Mycobacterium leprae chemotherapy in leprosy control programs. PMID- 1522368 TI - Role of rifampin and clofazimine ointments in the treatment of leprosy. AB - The use of rifampin and clofazimine ointments alone and in combination over the patches of tuberculoid patients had a beneficial effect. In combination (rifampin and clofazimine), erythema, inflammation, and edema are considerably reduced. For some of the cases with a recent appearance of a patch, the patch completely disappeared. It is suggested that topical therapy with rifampin and clofazimine ointments would be economical and beneficial in tuberculoid leprosy. PMID- 1522369 TI - Severe thrombocytopenia and intermittent use of rifampin. PMID- 1522370 TI - Giant histoid tumor. PMID- 1522371 TI - Minimal bactericidal dietary concentration of minocycline for Mycobacterium leprae-infected mice is very low and similar to its minimal inhibitory dietary concentration. PMID- 1522372 TI - Improved method for purification of Mycobacterium leprae from armadillo tissues. PMID- 1522373 TI - Water soluble palmitic acid-methylated cyclodextrin complex; a substrate oxidized by Mycobacterium leprae. PMID- 1522374 TI - Avidin-biotin immunoblotting studies on reactivity of leprosy sera with Mycobacterium leprae antigen. PMID- 1522375 TI - Autoradiographic evidence of reduced epidermal cell proliferation in leprosy patients. PMID- 1522376 TI - [Initial symptoms and diagnosis of early squamous cell carcinomas of the oral mucosa]. PMID- 1522377 TI - [Study on mandibular position in occlusion during opening and closing movement in hemimandibulectomy patients--effect of difference of opening distance on mandibular position]. AB - In the hemimandibulectomy patients the mandible is severely deviated and the occlusion is unstable, therefore the prosthodontic treatment for these patients is generally not successful. To investigate the stability of the mandibular position in occlusion of these patients, the differences of the range and the position of the mandible in occlusion between during the 5-mm opening and closing movement and during the 10-mm movement were analyzed three-dimensionally with the Jaw Movement Analyzer MM-JI-E. In this study, four hemimandibulectomy patients were selected as the subjects. The findings were as follows: 1. In three subjects, the range of the mandible in occlusion during the 10-mm opening and closing movement was larger than that during the 5-mm movement in almost all directions. On the contrary in one subject, the range of the mandible in occlusion during the 10-mm opening and closing movement was smaller than that during the 5-mm movement in almost all directions. 2. The relative relationship of the mandibular position in occlusion during the 10-mm opening and closing movement to that during the 5-mm movement varied in four subjects. In one subject, the mandible rotated horizontally towards the outside and moved upward. In another subject, the mandible rotated horizontally towards the inside and moved downward. In the other subject, the mandible moved inward and upward. In the other subject, the mandible moved outward and downward. PMID- 1522378 TI - [Clinical and microbiological study of factors determining effective scaling and root planing]. AB - The aim of the present study was to monitor longitudinally the clinical and microbiological parameters after root debridement in order to determine the factors affecting successful and unsuccessful results. Nine patients with moderate and severe periodontitis participated. Four sites of single root with over 5-mm periodontal pockets in each quadrant were selected. The oral hygiene was controlled in all patients, then root debridement was performed without anesthesia at the three sites of the quadrants every two weeks during eight weeks. The clinical parameters consisted of plaque index, gingival index, probing depth, clinical attachment level, bleeding on probing, tooth mobility and the value of gingival crevicular fluid (GCF). The microbiological parameters such as percentages of cocci, motile rods, non-motile rods and spirochetes and the number of microorganisms were examined and the percentages of black pigmented Bacteroides (BPB) and Actinobacillus actinomycetemcomitans as well as the number of anaerobic colonies were counted. The results demonstrated that a reduction in the probing depth was observed in all sites except four. The successful sites clinically showed a decrease of the probing depth and GCF value and, microbiologically, reduced percentages of the spirochetes and BPB. The results indicated that the decrease of the probing depth and GCF under 50 Periotoron units in coincidence with the bacterial reduction can be used to determine the successful response of root debridement. PMID- 1522379 TI - [Anatomical observations on the attachment of human temporalis and masseter muscles]. AB - It is very important for orthodontics to investigate the bone remodeling pattern in the area of the attachment of the masticatory muscles induced by the changing muscular function. In the present study, the insertion pattern of Sharpey's fibers and the bone structure are comparatively studied on the temporalis and the masseter muscles macroscopically, light microscopically and electron microscopically, respectively. The following results are obtained: 1) The periosteum on the squamous part of the temporal bone is thinner, while the one on the lower ridge of the zygomatic arch is relatively thicker. 2) The fine and loose Sharpey's fibers are found mostly on the squamous part of the temporal bone, while the ones on the lower ridge of the zygomatic arch are relatively coarse and dense. 3) Comparing with the squamous part of the temporal bone, the fibrous bone is thinner and also few reversal lines and resting lines are observed at the lower ridge of the zygomatic arch. These findings seem to prove the fact that the bone remodeling proceeds frequently within the limited narrow area. These differences are directly due to the differences of the anatomical site and the muscular function. PMID- 1522380 TI - [Histological observations on structure of endomysium, perimysium and epimysium of lateral pterygoid muscle in rat]. AB - To understand the muscle as a locomotorium, I observed the structure of the connective tissue sheaths (the endomysium, the perimysium and the epimysium) in the mature rat lateral pterygoid muscle. The following results were obtained using the macroscopy and light and electron microscopy. The lateral pterygoid muscle consists of two parts. The superior head originates from the basisphenoid and is mainly inserted into the articular disk and capsule. The inferior head originates from the lateral pterygoid processus and is mainly inserted into the condylar processus of the mandible. The perimysium is thick and bound the fasciculus secondarily as sheaths near the insertion of the superior head. The collagenous fibers are very fine in the endomysium. The collagenous fibers that make the connective tissue sheaths arrange on a skew against the muscle fibers, but parallel around the origin and the insertion. It seems that the connective tissue sheaths in the rat lateral pterygoid muscle, in view of the morphology, retain the forms of fasciculus, act as the runways for the muscle fibers in time of expansion and contraction and offer spaces for the attachment of the muscle fibers. PMID- 1522381 TI - [Fundamental studies on biological effects of dental metals--nickel dissolution, toxicity and distribution in cultured cells]. AB - In an oral environment, minute amounts of constituent metals dissolve from the surfaces of restorations. The uptake of the metals through the mucosa may cause systemic or local effects. The purpose of this study was to investigate these effects and mechanisms, focusing on the nickel as a dental metal. A nickel chromium dental casting alloy was stored in 3 immersion solutions for 4 weeks and the amount of nickel dissolved was measured. NiCl2 was administrated to the cultured medium to examine the cytotoxicity for HeLa cells and periodontal ligament-derived cells as well as the nickel distribution in the HeLa cells. The results were as follows: 1. The amounts of nickel released from the alloy were 1.2 micrograms/cm2 (human saliva), 2.0 micrograms/cm2 (PBS (-)) and 2.5 micrograms/cm2 (MILLI-Q water). 2. 3.0 mM NiCl2 showed a large cytotoxicity resulting in the cell growth rate and morphological changes. 3. Incubated for 72 hours in 0.15 mM NiCl2, the amount of nickel in the 10(6) cells was 20 ng. After 24 hours of incubation with NiCl2, and the following 72 hours without NiCl2, the amount of nickel had decreased, but 30% still remained. 4. Incubated for 72 hours in 0.15 mM NiCl2, 65% of the nickel in the cells was bound by the soluble fraction. These results suggest that nickel released from the oral prosthesis may be sequestered for a long term in the cells and possibly causes some effects. PMID- 1522382 TI - [Histological study of tissues surrounding an overloaded mandibular apatite implant and its antagonist teeth at three months]. AB - The objective of this study is to compare the degree of the occlusal-bearing ability of 2-piece apatite implant to that of natural dentition. It is conducted by placing implants at M2 and M2 areas of adult monkey. Four months later, the occlusal vertical dimension was raised to apply the occlusal force only on the implants by inserting connected crowns on M3M2M1 and M1M2M3. Three months after loading, the tissues surrounding the implants and the antagonist teeth were histologically examined. RESULTS: The antagonist teeth: The connected antagonist teeth show much bone resorption on the inner surface of the alveolar wall and the roots are partly in direct contact with the bone and intruded. Implant: 1. Due to the resorption from extraction, enhanced remodeling is seen in the compact bone of the experimental site. The degree of remodeling is higher toward the coronal direction. 2. Realigned functionally oblique toward the implant, thickened trabeculae, of both the lamellae and woven bone, supported the implant. 3. Bone formed widely on the buccal and lingual surfaces of the compact bone near the implant. In the areas of close to the direct contact of the implant to the compact bone, remodeling with osteon realignment in the axial direction was observed. 4. Most embedded surfaces of the implant were covered and bound to the bone. PMID- 1522383 TI - [Masticatory training with chewing gum on young children]. AB - Mastication is a developmental function. It matures through learning experiences. The biting force is one of the components of masticatory function. The biting force increases with age. During the developmental stage, it is believed feasible to enhance the maturation of the masticatory function by increasing the biting force. The previous results of masticatory training for adults and school children had revealed 20% to 30% increase of the biting force. In this study, masticatory training with specially fabricated chewing gum for young (preschool) children was performed. The subjects were 5 males and 5 females from 3 years old to 5 years old. These children were instructed to bite on the chewing gum for 5 minutes, 2 times a day, for 3 months. The results show that there was a 94% average increase of biting force after 3 months of training. It was also noted that the rate of the increase of the biting force was remarkable during the first month of training. PMID- 1522384 TI - [Studies on dimensional accuracy of working casts made by various impression techniques--influence of undercuts on dimensional accuracy]. AB - The purpose of this research was to evaluate the clinical acceptability of various impression techniques by comparing the dimensional accuracy of their working casts. An original metallic model was designed for this experiment. It has reference points to overlap and compare the master model and the working casts for measuring their dimensional accuracy under the same condition. The amount of distortion in each area of the working casts was examined by the measuring points within the model. The master model simulated an abutment for a full veneer crown with undercuts between the adjacent teeth. It was planned so that the amount of undercuts and distances between the adjacent teeth could be changed. As a result, a small distortion of the working casts due to the undercuts was observed by the technique using an individual tooth tray and polysulfide rubber base impression material. There was no significant dimensional change in the working casts made with silicone rubber base material. For the working casts made by hydrocolloid-alginate combination technique, the dimensional change was greater and distortion was observed in the abutment cast when the undercuts of the adjacent teeth were great. However, the distortion was less when the undercuts were small. PMID- 1522385 TI - Nitric oxide production by tumor targets in response to TNF: paradoxical correlation with susceptibility to TNF-mediated cytotoxicity without direct involvement in the cytotoxic mechanism. AB - Tumor necrosis factor (TNF) is selectively cytotoxic for some tumor cells in vivo and in vitro. We determined whether TNF-mediated cytotoxicity for TNF-sensitive tumor targets was related to TNF-stimulated production of NO by the tumor cell itself. We found that a cell line that was sensitive to TNF-mediated cytotoxicity produced NO in response to TNF as measured by the accumulation of nitrite in the supernatants of TNF-stimulated cells. Production of NO in response to TNF was inhibited by the competitive substrate inhibitor, NG-monomethyl-L-arginine (NMMA). The kinetics of NO production in response to TNF indicated that most of the NO was produced during the first 24 h and peaked after 48 h of culture and that TNF-stimulated NO production was dose dependent. TNF-resistant cell lines produced less NO than a TNF-sensitive cell line, and the amount of nitrite produced correlated with the relative sensitivity of each cell line to TNF mediated cytotoxicity. In addition, recombinant interferon-gamma augmented the amount of NO produced in response to TNF by both sensitive and resistant cells and correspondingly enhanced the susceptibility of resistant cells to TNF cytotoxicity. Both sensitive and resistant cells were sensitive to NO, however, in that NO generated exogenously by culture in the presence of sodium nitroprusside was cytotoxic for both sensitive and resistant cells in a dose dependent manner. We were unable, however, to demonstrate directly a role for NO in TNF-mediated cytotoxicity as NMMA- and arginine-free media provided little protection from TNF-mediated cytotoxicity. We tentatively conclude that the ability of adherent murine tumor cells to produce nitric oxide in response to TNF correlates directly with their level of sensitivity to TNF-mediated cytotoxicity, although NO thus produced appears not to be directly involved in the cytotoxic mechanism. PMID- 1522386 TI - Phagocytosis of apoptotic neutrophils does not induce macrophage release of thromboxane B2. AB - Senescent human neutrophils undergo programmed cell death (apoptosis), leading to their recognition and phagocytosis by mature macrophages. At inflamed sites in vivo these processes may represent a neutrophil removal mechanism with the potential to limit the histotoxic capacity of these cells. Phagocytosis can provoke marked proinflammatory responses by macrophages. A macrophage proinflammatory response to the ingestion of apoptotic neutrophils would limit the efficacy of this neutrophil removal mechanism as a component of inflammatory resolution. In the present study we examined two macrophage proinflammatory responses; secretion of the granule enzyme N-acetyl-beta-D-glucosaminidase (NAG) and release of the membrane lipid-derived inflammatory mediator thromboxane A2 (TxA2, measured as TxB2). By contrast with the marked release of NAG and TxB2 elicited by phagocytosis of control particles (opsonised zymosan and immunoglobulin G-coated erythrocytes), macrophage ingestion of apoptotic neutrophils resulted in minimal release of NAG and no release of TxB2; indeed, there was a small depression of TxB2 release that was not due to a toxic effect of neutrophil uptake because macrophages ingesting apoptotic neutrophils retained marked TxB2 responses to subsequent stimulation with opsonised zymosan. Furthermore, there was significant TxB2 release in response to macrophage phagocytosis of apoptotic neutrophils that had been coated with opsonic serum, demonstrating that the lack of macrophage response was determined by the mechanism of recognition rather than the properties of the apoptotic particle itself. These observations are consistent with the hypothesis that macrophage clearance of senscent neutrophils undergoing apoptosis is an injury-limiting mechanism that favors resolution rather than persistence of the inflammatory response and are consistent with observations that the waves of apoptotic cell removal seen in embryological removal and thymic involution do not trigger an inflammatory response. PMID- 1522387 TI - Constitutive production of PAI-II and increased surface expression of GM1 ganglioside by peripheral blood monocytes from patients with AIDS: evidence of monocyte activation in vivo. AB - To characterize the activation state of monocytes during human immunodeficiency virus (HIV) infection, peripheral blood monocytes (PBMs) from patients with acquired immunodeficiency syndrome (n = 10) and from healthy controls (n = 10) were cultured for 4 days. Monocyte culture supernatant (MCS) was collected daily, and levels of urokinase (UK) inhibitor PAI-II, a product of activated monocytes, released into MCS were determined (fibrin plate assay). To examine the activation state of PBMs independently, expression of GM1 ganglioside on PBMs from patients with AIDS (n = 9), patients with AIDS-related complex (ARC) (n = 8), HIV+ asymptomatic patients (n = 6), and HIV- healthy controls (n = 11) was determined (flow cytometry; living cells in suspension). Data are expressed as percent inhibition of UK, or as percent total cells. Patients' MCS collected on days 1-4 of culture contained similar levels of PAI-II because it inhibited UK in similar fashion (70-90%). In contrast, MCS from healthy controls, collected after 2 days, had decreased ability to inhibit UK (15-50%) and thus contained lower levels of PAI-II. Monocyte activation, measured by increased expression of GM1 ganglioside on PBM surfaces, directly correlated with the progression of HIV infection into the development of AIDS, since the order of magnitude of GM1 ganglioside expression on PBMs was AIDS greater than ARC greater than HIV+ asymptomatic = healthy controls. Our data indicate that PBMs from patients with AIDS are constitutively activated and suggest that activation directly correlates with disease progression. PMID- 1522388 TI - Heterogeneity of rat liver and spleen macrophages in gadolinium chloride-induced elimination and repopulation. AB - Blockade of phagocytosis and selective elimination of macrophages (m phi s) are generally accepted procedures for gaining knowledge about the function of m phi s in vivo. This study demonstrates that intravenous injection of gadolinium chloride (GdCl3) not only blocks phagocytosis by rat liver m phi s (Kupffer cells) but also selectively eliminates the large m phi s situated in the periportal zone of the liver acinus. Repopulation of m phi s starts at 4 days after injection. During repopulation, m phi s are less vulnerable to GdCl3. When repopulation is complete, the new m phi s show the same vulnerability as the original ones. Splenic m phi s are less vulnerable to GdCl3 because only some of the red pulp m phi s transiently disappear. The white pulp m phi s are not affected. Repopulation occurs sooner than in liver. These results indicate that administration of GdCl3 is a suitable approach to studying the in vivo function of large Kupffer cells. PMID- 1522389 TI - Macrophage inflammatory proteins MIP-1 and MIP-2 are involved in T cell-mediated neutrophil recruitment. AB - Mice intraperitoneally (i.p.) infected with Mycobacterium bovis bacille Calmette Guerin (BCG) respond to an i.p. challenge with mycobacterial antigen with an acute and extensive accumulation of neutrophils. This influx was not mimicked by the inoculation of recombinant interferon-gamma (IFN-gamma) or tumor necrosis factor alpha (TNF-alpha). The antigen-induced recruitment of neutrophils was not affected by coinoculation of anti-IFN-gamma antibodies, was enhanced by anti-TNF alpha antisera, and was significantly reduced by antisera against macrophage inflammatory proteins MIP-1 and MIP-2. The latter two sera had no additive effects. We hypothesize that mycobacteria-specific T cells are triggered by antigen to secrete MIP-1 and MIP-2, which directly mediate, at least partly, the influx of neutrophils that takes place in this model. PMID- 1522390 TI - Levamisole causes differential cytokine expression by elicited mouse peritoneal macrophages. AB - Thioglycolate-elicited peritoneal macrophages from normal C57B1/6J mice were examined in vitro for bacterial lipopolysaccharide (LPS)-stimulated interleukin-1 (IL-1), IL-6, and tumor necrosis factor (TNF) production. Macrophages from mice administered a single oral dose of levamisole (3 mg/kg) 1 to 4 days prior to macrophage harvest demonstrated a twofold enhancement of IL-1 production compared to vehicle-treated mice. In contrast, IL-6 production and TNF production by the same macrophages were inhibited up to 36 and 62%, respectively, compared to production by macrophages harvested from vehicle-treated mice. Similar results were observed when IL-1 production and TNF production were followed in peritoneal exidate cells directly stimulated with levamisole in vitro. The ex vivo LPS stimulated IL-1 production was enhanced 4 days after macrophage elicitation, whereas TNF and IL-6 production returned to baseline by 72 h after macrophage recruitment and augmentation. No evidence could be found for the presence of inhibitors of TNF or IL-6. The specificity of the IL-1, IL-6, and TNF bioactivities was demonstrated by neutralization with specific antisera. Immunoprecipitation studies of supernatants from biosynthetically labeled macrophages also revealed augmented IL-1 production and decreased IL-6 and TNF, indicating that levamisole may have affected cytokine production at the translational level. Kinetics studies revealed that ex vivo release of IL-6 and TNF by macrophages from levamisole-dosed mice was delayed compared to production of these cytokines by macrophages harvested from mice given vehicle only. The results may explain, in part, the reported ability of levamisole to ameliorate cases of rheumatoid arthritis or other autoimmune and inflammatory diseases by affecting the relative levels of cytokines produced by macrophages recruited to sites of injury, which are associated with inflammation and acute-phase protein synthesis. PMID- 1522392 TI - Dynamic models of infectious diseases as regulators of population sizes. AB - Five SIRS epidemiological models for populations of varying size are considered. The incidences of infection are given by mass action terms involving the number of infectives and either the number of susceptibles or the fraction of the population which is susceptible. When the population dynamics are immigration and deaths, thresholds are found which determine whether the disease dies out or approaches an endemic equilibrium. When the population dynamics are unbalanced births and deaths proportional to the population size, thresholds are found which determine whether the disease dies out or remains endemic and whether the population declines to zero, remains finite or grows exponentially. In these models the persistence of the disease and disease-related deaths can reduce the asymptotic population size or change the asymptotic behavior from exponential growth to exponential decay or approach to an equilibrium population size. PMID- 1522391 TI - Oscillations in a model of repression with external control. AB - A mathematical model for control by repression by an extracellular substance is developed, including diffusion and time delays. The model examines how active transport of a nutrient can produce either oscillatory or stable responses depending on a variety of parameters, such as diffusivity, cell size, or nutrient concentration. The system of equations for the mathematical model is reduced to a system of delay differential equations and linear Volterra equations. After linearizing these equations and forming the limiting Volterra equations, the resulting linear system no longer has any spatial dependence. Local stability analysis of the radially symmetric model shows that the system of equations can undergo Hopf bifurcations for certain parameter values, while other ranges of the parameters guarantee asymptotic stability. One numerical study shows that the model can exhibit intracellular biochemical oscillations with increasing extracellular concentrations of the nutrient, which suggests a possible trigger mechanism for morphogenesis. PMID- 1522393 TI - Disease transmission models with density-dependent demographics. AB - The models considered for the spread of an infectious disease in a population are of SIRS or SIS type with a standard incidence expression. The varying population size is described by a modification of the logistic differential equation which includes a term for disease-related deaths. The models have density-dependent restricted growth due to a decreasing birth rate and an increasing death rate as the population size increases towards its carrying capacity. Thresholds, equilibria and stability are determined for the systems of ordinary differential equations for each model. The persistence of the infectious disease and disease related deaths can lead to a new equilibrium population size below the carrying capacity and can even cause the population to become extinct. PMID- 1522394 TI - Rapidly converging numerical algorithms for models of population dynamics. AB - We propose algorithms for the approximation of the age distributions of populations modeled by the McKendrick-von Foerster and the Gurtin-MacCamy systems both in one- and two-sex versions. For the one-sex model methods of second and fourth order are proposed. For the two-sex model a second order method is described. In each case the convergence is demonstrated. Several numerical examples are given. PMID- 1522395 TI - Application of computerized exercise ECG digitization. Interpretation in large clinical trials. AB - The authors report on a semiautomated program that incorporates both visual identification of fiducial points and digital determination of the ST-segment at 60 ms and 80 ms from the J point, ST slope, changes in R wave, and baseline drift. The off-line program can enhance the accuracy of detecting electrocardiographic (ECG) changes, as well as reproducibility of the exercise and postexercise ECG, as a marker of myocardial ischemia. The analysis program is written in Microsoft QuickBASIC 2.0 for an IBM personal computer interfaced to a Summagraphics mm1201 microgrid II digitizer. The program consists of the following components: (1) alphanumeric data entry, (2) ECG wave form digitization, (2) calculation of test results, (4) physician overread, and (5) editor function for remeasurements. This computerized exercise ECG digitization interpretation program is accurate and reproducible for the quantitative assessment of ST changes and requires minimal time allotment for physician overread. The program is suitable for analysis and interpretation of large volumes of exercise tests in multicenter clinical trials and is currently utilized in the TIMI II, TIMI III, and BARI studies sponsored by the National Institutes of Health. PMID- 1522396 TI - Conduction of early afterdepolarizations in sheep Purkinje fibers and ventricular muscle. An in vitro arrhythmia model. AB - To establish an arrhythmia generator model, a double-chambered bath was used in which sheep Purkinje fibers (PF) and ventricular muscle (VM) were placed. The conduction patterns of early afterdepolarization-induced triggered activations (TAs) were examined between normal segments bathed in unmodified Tyrode solution and abnormal segments bathed in ethylenediaminetetraacetate (3.3-5.0 mmol). Three types of preparations were used: PF-PF (n = 10), VM-VM (n = 5), and PF-VM (n = 13). Two types of spontaneous TAs appeared. One type was conducted to normal segments, inducing activations over the entire preparation, while the other type was not conducted. The conducting TAs had significantly more rapid mean dV/dt, larger amplitude, and higher peak transmembrane voltage as compared to nonconducting TAs. While conduction occurred in all PF-PF, VM-VM, and PF-VM preparations, conduction of TAs from abnormal segment VM to normal segment PF was impaired. A low plateau resulting from electrotonic transmission of depolarizing current from abnormal segments was recorded in normal segments near the border. This low plateau probably facilitated the transmission of TAs. In addition to spontaneous TAs, stimulated or spontaneous action potentials from NL were conducted to the not yet fully repolarized ABN and induced activations resembling TAs. These results may be relevant to clinical arrhythmias due to action potential prolongation. The arrhythmia may occur directly as a result of triggered activity or indirectly via slow conducting TAs, creating the possibility for reentry. This type of model may be useful for intervention studies, for example, by identifying agents that block abnormal segment to normal segment conduction. PMID- 1522397 TI - Discrimination between myocardial infarct and ventricular tachycardia patients using magnetocardiographic trajectory plots and iso-integral maps. AB - Magnetocardiograms were recorded from 30 normal (N) subjects, 15 myocardial infarct (MI) patients, and 15 ventricular tachycardia (VT) patients. Discrimination between the groups was affected by iso-integral magnetic field mapping (MFM) and trajectory plotting of MFM extrema. Iso-integral MFM for the QRST, QRS, and ST-T intervals was created for each test group member. A polarity score, based on the number of extrema features present, was assigned to each iso integral MFM. Differences in group mean integral of QRST map polarity scores were significant (p less than 0.05) between MI and N, between VT and N (p less than 0.005), and between MI and VT (p less than 0.05) subjects. integral of ST-T map polarity scores were significantly (p less than 0.0001) different between VT and N and between MI and VT (p less than 0.001) subjects. Discrimination between MI and VT patients, based on polarity score difference, was 56% accurate using integral of QRS maps and 73% accurate using integral of ST-T maps. For each subject, time-normalized MFM was used to construct trajectory plots of the maxima and minima in the QRS and ST-T intervals. Discrimination between MI and VT patients was based upon intergroup differences in fragmented trajectory plots. When the number of discrete trajectories and/or the total number (F) of trajectory points at which discrete trajectories coexist were considered, QRSmin trajectory plots were significantly (p less than 0.05) different for VT and N, but not for MI and N subjects. The significant (p less than 0.05) difference between MI and VT trajectory plots enabled 76% accuracy for MI and VT identification. ST-Tmax trajectory plots show significantly (p less than 0.0001) higher F values for VT patients facilitating accurate (87%) discrimination between MI and VT patients. These results suggest that the abnormalities of repolarization processes, displayed by MFM as multipolar integral of ST-T maps and/or as fragmented trajectory plots of ST-T extrema, may be useful indicators of the arrhythmia substrate/processes that characterize VT and vulnerable MI patients. PMID- 1522398 TI - Localization of accessory pathways in Wolff-Parkinson-White syndrome by high resolution magnetocardiographic mapping. AB - Fifteen patients with Wolff-Parkinson-White syndrome were studied with standard 12-lead electrocardiogram, invasive electrophysiologic study, and high-resolution magnetocardiographic (MCG) mapping. In addition, intraoperative epicardial mapping was performed in seven surgically treated patients. The MCG characteristics of ventricular preexcitation for different locations of the atrioventricular accessory pathways were described in terms of morphology and field patterns. Three mathematical source models in semi-infinite conducting space were used for localization computations: the current dipole model, the truncated current multipole model and the magnetic dipole model. Finally, the localization results of MCG and invasive mappings and electrocardiograms were compared. The mean three-dimensional distance between the localization results obtained from MCG maps and electrophysiologic study was 3.9 cm for the magnetic dipole model, 4.8 cm for the truncated current multipole model, and 7.3 cm for the current dipole model. The corresponding distances in the seven intraoperatively mapped cases were 2.3 cm for the magnetic dipole model, 5.2 cm for the truncated current multipole model, and 6.3 cm for the current dipole model. In conclusion, noninvasive MCG mapping may significantly contribute to the invasive catheter mapping for optimal preoperative localization of preexcitation site and atrioventricular accessory pathways in Wolff-Parkinson-White syndrome. PMID- 1522399 TI - Nomina anatomica contradicta. Especially as relates to the heart and electrocardiology. PMID- 1522400 TI - Giant negative U waves in a patient with uncontrolled hypertension and severe hypokalemia. AB - A 66-year-old woman with a long history of hypertension had an electrocardiogram with giant negative U waves in left precordial leads despite hypokalemia. This seems to be the first report of giant negative U waves induced by uncontrolled hypertension with hypokalemia. The occurrence of negative U waves in the presence of profound hypokalemia is an important observation because it masks the electrocardiographic manifestation of hypokalemia. PMID- 1522401 TI - Heart rate variability in patients with diabetes mellitus, ischemic heart disease, and congestive heart failure. AB - The prognosis of patients with heart disease and prediction of sudden cardiac death can be assessed through heart rate variability, an indirect measure of abnormal autonomic control. The authors have evaluated the heart rate variability by 24-hour ambulatory electrocardiographic monitoring in 25 diabetic patients, 19 ischemic heart disease patients, 18 congestive heart failure patients, and 10 normal subjects. Thirteen diabetic patients had autonomic neuropathy and 12 patients did not. Heart rate variability index (mean SD) in patients with diabetes mellitus, ischemic heart disease, and congestive heart failure was significantly lower (34.5 +/- 12.6 ms, 43.7 +/- 15.4 ms, and 34.6 +/- 15.8 ms vs 65.6 +/- 16.7 ms, p less than 0.05) than that of normal subjects. Mean SD was significantly lower in patients with autonomic neuropathy as compared to patients without autonomic neuropathy (26.4 +/- 6.5 ms vs 44.2 +/- 11.0 ms, p less than 0.05) mean SD as compared to survivors: 49 +/- 7 ms in patients with mild ischemic heart disease, 48 +/- 15 ms in patients with severe ischemic heart disease, and 23 +/- 7 ms in patients who died. Similarly, the mean SD in 4 congestive heart failure patients who died was lower significantly (p less than 0.05) than in those who survived (19.0 +/- 5.6 ms vs 40.0 +/- 14.5 ms). Among congestive heart failure patients, clinical improvement by therapy was associated with a significant increase in mean SD. When the mean SD of 30 ms was used as the cutoff point for detection of autonomic dysfunction or patient death, specificity exceeded 90% and sensitivity was 75%.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1522402 TI - Comparison of logistic regression and Bayesian-based algorithms to estimate posttest probability in patients with suspected coronary artery disease undergoing exercise ECG. AB - Two multivariate methods, a logistic regression-derived algorithm and a Bayesian independence-assuming method (CADENZA), were compared concerning their abilities to estimate posttest probability of coronary disease in patients with suspected coronary disease. All patients underwent exercise testing within 3 months prior to coronary angiography. Coronary disease was defined as the presence of one or more vessels with greater than or equal to 50% luminal diameter narrowing. A group of 300 patients (disease prevalence = 37%) was used to derive the algorithm. Another group of 950 patients was used to validate the algorithm and compare it to CADENZA. Seven variables (age, sex, symptoms, diabetes, mm ST depression, ST slope, and peak heart rate) were used to generate posttest probabilities for each method. The receiver operating characteristic curve area for the logistic regression method (0.81 +/- 0.01) was significantly higher than CADENZA (0.75 +/- 0.01; p less than 0.05). There was, however, no difference in the calibration of the two methods. When given equivalent variable information, the logistic regression algorithm had better discrimination than CADENZA for estimating the probability of coronary disease following exercise electrocardiography. PMID- 1522403 TI - Factors associated with recidivism in a criminal population. AB - The present study is a follow-up of a sample of 348 men convicted of manslaughter, attempted manslaughter, or arson who were released from incarceration. Multiple factors assessed at the time of incarceration, including demographic, behavioral, family history, and biochemical variables, and psychiatric diagnoses were used in an attempt to discriminate between those who became recidivists during the follow-up period and those who did not. Violent recidivism was most strongly associated (sensitivity of 90%) with impulsivity of the original crime in killers and attempted killers; for arsonists, having made a suicide attempt was the strongest predictor (68% sensitivity). For predictive purposes, both single factor associations and multiple entries into discriminant analysis produced too many false-positives, i.e., the high rate of false designation as recidivist remained a problem. PMID- 1522404 TI - An analysis of treatment services provided in group homes for adults labeled mentally ill. AB - Although group homes for adults labeled mentally ill have been the focus of significant attention in deinstitutionalization discussions, substantive research on their operation has been lacking. The present study addresses past limitations by focusing on a well-defined sample of small group homes, with higher staffing levels and in-home treatment provided. Thirty homes were randomly selected; all home residents (N = 253) were studied. Data were collected from case managers, residents, and home staff to assess residents' functioning, services and treatments provided, and the environment of the home. The findings were examined in terms of adequacy and appropriateness of care provided in the home, using accepted guidelines. The results indicated that there are aspects of a homelike environment, emotional support from staff, and skill-development activities within the home. However, an institutional focus still seems prevalent, along with limited rehabilitation and socialization activities. Residents expressed high levels of satisfaction, which may reflect their dislike of the group home alternative, e.g., the state hospital. Policy implications are discussed vis-a vis current efforts to move away from group homes toward supported housing initiatives. PMID- 1522405 TI - The National Institute of Mental Health Panic Questionnaire. An instrument for assessing clinical characteristics of panic disorder. AB - This paper introduces a new self-report inventory, the NIMH Panic Questionnaire (NIMH PQ), for obtaining and quantifying comprehensive information about the clinical characteristics of panic disorder in patients with previously diagnosed or suspected illness. Fifty-two patients who met DSM-III-R criteria for panic disorder completed the NIMH PQ; their responses were compared with data derived from 16 similar or identical questions on the Schedule for Affective Disorders and Schizophrenia modified for anxiety disorders. There were no significant differences between the two instruments on 15 of the 16 (93.7%) items tested. The one exception revealed a greater proportion of patients versus physicians endorsing "spontaneous" panic, and a nonsignificant trend for physicians over patients endorsing anticipatory anxiety with greater frequency. The NIMH PQ offers a potentially useful clinical and research tool in the assessment of patients with known or suspected panic disorder. PMID- 1522406 TI - Depression in Korean immigrants in Canada. I. Method of the study and prevalence of depression. AB - This study reports the prevalence and risk factors of depression in a large representative community sample of adult Korean immigrants in Toronto, Canada. The Center for Epidemiologic Studies-Depression scale was used to measure depression by applying DSM-III criteria. Results in general suggest few differences between the immigrant community and the larger communities in Canada and the United States. Depressive syndrome was present in 4.5% of the sample, a prevalence similar to rates reported by the Epidemiologic Catchment Area studies. The risk factors associated with depression in larger populations were also found to be related to depression in this sample. Gender, marital status, intention to re-migrate, and social support were the most powerful correlates of depressive syndrome. In summary, Korean immigrants in Toronto are not exceptionally vulnerable to depression, and the social support from informal ethnic networks at the time of arrival has long-lasting effects on their mental health. Future research should focus on how the informal social supports available at the time of arrival are maintained by immigrants and the precise ways in which they exert long-term protective effects. PMID- 1522407 TI - Depression in Korean immigrants in Canada. II. Correlates of gender, work, and marriage. AB - The Center for Epidemiologic Studies-Depression scale was used to measure depression by applying DSM-III criteria to a community sample of 860 adult Korean immigrants residing in Toronto, Canada. A total of 2.6% of men (95% confidence interval, 1.1% to 4.1%) and 6.7% of women (95% confidence interval, 4.3% to 9.1%) manifested depressive syndrome, rates not substantially different from those reported in North American community populations. The study also identified the subgroups in which the gender differences in depression were the greatest. Both the role demand (or double burden) and power explanations of gender differences might be supported. The mental health implications of social roles, including gender role, may be better understood from cross-cultural or multicultural perspectives. PMID- 1522408 TI - Is risk for substance abuse unitary? AB - The hypothesis that risk for substance abuse is not unitary was tested by a log linear regression analysis. A series of risk factors was evaluated in a sample of 219 nonhospitalized, nontreated, young male and female subjects. Risk for alcohol abuse/dependence was independent of risk for drug abuse/dependence and the risks were additive in the prediction of lifetime substance abuse. Antisocial personality diagnosis predicted alcohol abuse/dependence, family history of drug abuse predicted drug abuse/dependence, and, additively, they predicted alcohol and drug abuse/dependence diagnosis over a lifetime. These data support a hypothesis that risk for substance abuse is not unitary. PMID- 1522409 TI - Prevalence estimates of substance abuse in schizophrenia and their correlates. AB - Published estimates of the prevalence of substance abuse in schizophrenia were correlated with several aspects of the studies in which they were obtained. Higher estimates of alcohol and stimulant abuse were found in studies published more recently. Rates of alcohol abuse were particularly high in one rural investigation. Rates of stimulant abuse were highest when patients were asked directly about use of stimulants. Increased prevalence estimates in more recent years could not be attributed to method of assessing substance abuse, method of defining substance abuse, or characteristics of the study sample. PMID- 1522410 TI - Commentary. DSM diagnosis of posttraumatic stress disorder and cultural sensitivity: a response. PMID- 1522411 TI - Commentary. Posttraumatic stress disorder among injured survivors of a terrorist attack: predictive value of early intrusion and avoidance symptoms. PMID- 1522412 TI - Valproic acid for nonaffective aggression in the mentally retarded. PMID- 1522413 TI - Delusional disorder and Charcot-Marie-tooth disease. PMID- 1522414 TI - Ligational behavior of N-substituted acid hydrazides towards transition metals and potentiation of their microbiocidal activity. AB - New complexes of Cu(II), Ni(II), and Co(II) with 3-benzoyl-1-[2-N-(substituted-2' thienyl methylmethylene/methylene)] prop-2-ene-1-oic acid hydrazides have been synthesized and characterized by elemental analysis, molecular weight determination, molar conductance, and magnetic moment and spectroscopic techniques. Conductance measurements indicate the nonionic nature of the complexes. From the spectroscopic studies, it has been concluded that the N substituted acid hydrazides act as tridentate ligands forming an O-N-S conjugate system and coordinating with metal ions through oxygen of carbonyl group, nitrogen of azomethine, and sulphur of thiophene moiety. Octahedral geometry has been proposed for all the complexes. The ligands and their complexes were tested for in vitro growth inhibitory activity against phytopathogenic fungi viz. Alternaria alternata, Colletotrichum capsicum, Fusarium oxysporum, and Rhizoctonia solani at 28 degrees C; and bacteria viz. gram positive Bacillus subtilis and gram negative Escherichia coli at 37 degrees C by a two-fold serial dilution technique. In some cases an increase in the biocidal activity of the ligands as a consequence of coordination with metal ions was observed in terms of minimum inhibitory concentration (MIC) values. The trend of growth inhibition in the complexes was found to be in the order: Cu greater than Ni greater than Co. PMID- 1522415 TI - The binding of polyamines and magnesium to DNA. AB - 1. The binding of spermine and Mg2+ to DNA has been investigated using the dye arsenazo III to measure unbound cations. 2. The apparent dissociation constant, Kd, of DNA for spermine has been found to be 7.4 +/- 3.9 x 10(-8) M and that for Mg2+, 6.5 +/- 3.3 x 10(-7) M. 3. Binding of spermine in the presence of 1 mM Mg2+ has been shown to have a Kd of about 4 x 10(-6) M. 4. Magnesium ion (2 mM) halves the concentration of spermine needed to cause DNA aggregation. 5. Spermidine binds to DNA with a similar affinity to spermine but 3,3'-iminobispropylamine and 1,5,9,13-tetra-azatridecane bind with a lower affinity. The naturally occurring polyamines thus have a higher affinity for DNA than the related polyamines which do not occur naturally. 6. Binding of spermine or spermidine to DNA alters the spectrophotometric absorbance of DNA at 260 nm. PMID- 1522416 TI - Arsenic-75 nuclear magnetic resonance: study of the interaction of arsenate with various molecules of biological interest. AB - 75As NMR (Nuclear Magnetic Resonance) was used as a probe of arsenate interactions in solution. The linewidth at half-height of the 75As NMR signal of arsenate was studied as a function of solution pH and temperature. Below pH 11.5, the 75As signal was too broad to be detected, but at higher pH, up to pH = 13.5, the signal became much narrower. This indicates that the arsenate species AsO4(3 ) is quite symmetric, but the asymmetry of HAsO4(2-) is sufficient to cause extensive quadrupolar relaxation of the 75As nucleus. A full pH range 75As and proton NMR study of the interaction of arsenate with ethanol, ethylene glycol, glycerol, ribose, mannose, glucose, gluconic acid and acetate was undertaken in order to follow arsenate ester formation. The 75As line broadening effects and the proton ligand shifts observed indicate that complexation of arsenate by ribose, mannose, glucose, ethanol, ethylene glycol, and glycerol occurs at pH 12.7. However, no significant interaction is detected by NMR with gluconic acid or acetate. The effect of the nucleoside adenosine is quite small and those of phosphate and of the nucleotides AMP and ADP are negligible. The interaction of arsenate with potential cationic centers, such as the basic amino acids lysine and arginine and some macrocyclic triamines, was also studied. Such interaction depends on the pKa for protonation of the amine groups. PMID- 1522417 TI - A new class of alkaloids from a dendrobatid poison frog: a structure for alkaloid 251F. AB - Alkaloids of a new class are present in skin extracts of the dendrobatid poison frog, Minyobates bombetes, of Colombia. The structure of the major alkaloid of this class, 251F, has been determined as a trimethylcyclopenta[b]quinolizidinemethanol 1 by nmr, gc-Ft-ir, and ms studies including ms-ms. At least nine congeners of 251F were detected in these extracts. PMID- 1522418 TI - Isolation and structure determination of new macrolide antibiotics. AB - Three new bafilomycin-like compounds PD 118,576-A1 [1], PD 118,576-A2 [2], and PD 118,576-A3 [3] were isolated from a new soil Streptomyces species (WP 3913). The structures of PD 118,576-A1, PD 118,576-A2, and PD 118,576-A3 were elucidated on the basis of spectroscopic studies including 2D nmr. PMID- 1522419 TI - Antibacterial activity of crinitol and its potentiation. AB - An acyclic diterpene alcohol, crinitol [1], was identified in a marine brown alga, Sargassum tortile, as the principal antibacterial agent against Gram positive bacteria, among which Propionibacterium acnes was most sensitive and, Staphylococcus aureus was least. To enhance its activity, crinitol was combined with several antioxidants, which presumably retard oxidative destruction of this molecule which possesses two easily oxidizable allylic alcohol groups. Two synthetic antioxidants, BHA (butylated hydroxyanisole) and BHT (butylated hydroxytoluene), significantly enhanced the activity of crinitol, especially against Streptococcus mutans. Interestingly, crinitol also synergized BHT and BHA against this cariogenic bacterium. PMID- 1522421 TI - Effect of ursolic acid from epicuticular waxes of Jacaranda decurrens on Schizaphis graminum. AB - Ursolic acid from Jacaranda decurrens showed toxicity and feeding deterrency towards the greenbug Schizaphis graminum. Biological activity was determined by analyzing ursolic acid effects on the survival, reproductive index, and population growth rate of the greenbug. Survival and reproductive index decreased in direct proportion to ursolic acid content in the diet. The population growth rate decreased markedly when the aphids were fed on barley leaves sprayed with ursolic acid dissolved in DMSO, in comparison to leaves sprayed only with DMSO. The feeding behavior of the greenbug was also affected by ursolic acid. Ingestion time on diet with 0.1 mM was reduced about 30% in relation to the ingestion time on control diet. PMID- 1522420 TI - Melandrioside A, a saponin from Melandrium firmum. PMID- 1522422 TI - Psammaplysin C: a new cytotoxic dibromotyrosine-derived metabolite from the marine sponge Druinella (= Psammaplysilla) purpurea. AB - The new, cytotoxic dibromotyrosine-derived metabolite psammaplysin C [3], in addition to the two known psammaplysins A [1] and B [2], was isolated from the marine sponge Druinella purpurea. All three compounds were found to possess moderate in vitro cytotoxicity towards the human colon tumor cell-line HCT116. PMID- 1522423 TI - Early discharge--early trouble. PMID- 1522424 TI - Evaluation of oxygen desaturation events in singleton pregnancies. AB - Previous investigators have demonstrated that oxygen desaturation may occur in laboring women. The purposes of this study were to identify groups at risk for desaturation and to seek correlation with newborn outcome. Volunteers in labor were evaluated for oxygen desaturation, analgesic exposure, magnesium sulfate administration, and various medical illnesses. Desaturations were noted more frequently in women exposed to narcotic analgesics, sedatives, and magnesium sulfate. A trend toward more desaturations in the women with preeclampsia was noted. Although desaturations related to narcotic analgesics and sedatives are most likely due to hypoventilation, the mechanism in women treated with magnesium sulfate is uncertain. Maternal peripartum desaturations did not result in unfavorable neonatal Apgar scores, cord blood gas measurements, or neonatal oxygen desaturation values, but the staff was aware of the events and prompt treatment was instituted. PMID- 1522425 TI - Cholelithiasis in infants receiving furosemide: a prospective study of the incidence and one-year follow-up. AB - Cholelithiasis has been reported to occur rarely in infants. To determine the incidence of cholelithiasis in infants receiving furosemide, we prospectively performed ultrasonograms on 86 patients. We studied 42 patients receiving furosemide (subjects) and 44 patients not receiving furosemide (controls). There was a significantly higher incidence of gallstones in subjects (21%) than in controls (2%) (P less than .05). When followed over 1 year, the gallstones did not resolve. There were no significant differences in the dosage of furosemide, gestational age, placement of umbilical venous catheters, or amount of total parenteral nutrition (TPN) between subjects with and without gallstones. However, subjects received more days of TPN (16.7 +/- 15.1) than controls (8.4 +/- 13.2) (P less than .05). These data show that the incidence of cholelithiasis is higher than previously suspected in infants receiving furosemide. Thus, furosemide, either independently or in conjunction with the use of TPN, predisposes infants to the development of cholelithiasis. PMID- 1522426 TI - Misdiagnosis of congenital chloride-losing diarrhea. AB - Congenital chloride-losing diarrhea is a recessively inherited disorder due to the absence of chloride-bicarbonate exchange in the small bowel. Malabsorption of chloride leads to osmotic diarrhea, electrolyte abnormalities, and dehydration. If left untreated, the infants fail to thrive and have a very high mortality. Clinically, affected patients develop secretory diarrhea in utero resulting in distended bowel loops and polyhydramnios. At birth these infants have profuse watery diarrhea that may be confused with urine. Thus, the correct diagnosis is often missed, and they may be subjected to unnecessary interventions. If diagnosed early, the electrolyte abnormalities are easily corrected and the prognosis is good. We report two patients who were initially evaluated for other conditions but later proved to have congenital chloride-losing diarrhea. The cases emphasize the importance of having a high index of suspicion in patients with a history of polyhydramnios, prematurity, and watery stools. PMID- 1522428 TI - Effects of saline instillation during tracheal suction on lung mechanics in newborn infants. AB - To evaluate the effect of saline instillation prior to tracheal suction on lung mechanics in mechanically ventilated newborn infants, we studied pulmonary mechanics in nine infants with respiratory distress syndrome (RDS) and nine infants with meconium-aspiration syndrome (MAS) at a mean postnatal age of 3 days. Pulmonary mechanics were measured at 10 minutes prior to, and at 10, 20, and 30 minutes after tracheal suction with saline instillation. Suction and study protocol were repeated within 12 hours without saline instillation. The sequence of the study with and without saline instillation was randomly assigned. In infants with RDS, tracheal suction had no effect on pulmonary compliance or airway resistance with and without saline instillation. In infants with MAS, there was no change in compliance after tracheal suction with and without saline instillation. Airway resistance decreased by 35% after tracheal suction with saline instillation in infants with MAS; tracheal suction without saline instillation had no effect on airway resistance. We conclude that saline instillation into trachea as commonly done during tracheal suction has no deleterious effects on lung mechanics in newborn infants. PMID- 1522429 TI - Apnea in subsequent asymptomatic siblings of infants who had an apparent life threatening event. AB - Infants experiencing apparent life-threatening events (ALTE) have been reported to have elevated frequencies of periodic breathing and obstructive apnea when compared to presumably normal control groups. Whether these characteristics extend to the siblings of ALTE infants remains unknown. This study compared, retrospectively, the apnea indices of 13 first-born infants experiencing an ALTE with their subsequent asymptomatic siblings who had undergone polygraphic sleep apnea evaluations (including electrocardiogram, chest wall movements, expired CO2, and transcutaneous pulse oximetry). Gestation, birthweight, age at study, apnea and periodic breathing indices, and oxygen desaturations were compared. Regression analyses revealed that adjustments for gestational and postnatal age eliminated differences in apnea indices. ALTE infants and their subsequent siblings experienced similar rates of apnea. Neither group had elevated rates of prolonged central apneas (greater than 10 seconds duration) or periodic breathing (greater than 5% sleep time). Neither group had subsequent severe apneas. The use of polygraphic study and cardiac/apnea monitors in subsequent siblings of ALTE are unnecessary and should be considered only when there is parental disagreement. PMID- 1522427 TI - Validity of postnatal assessments of gestational age in low birthweight infants from a Caribbean community. AB - The Dubowitz assessment of gestational maturity was compared with the best obstetric estimate of gestational age based on date of last menstrual period (LMP) or ultrasonography performed early in the pregnancy or both. This study involved 384 low birthweight infants admitted to the neonatal tertiary center in Guadeloupe, French West Indies, during the period 1986 through 1988. The Dubowitz assessment exceeded the best obstetric estimation by an average of nearly 5 days. This overestimation by the Dubowitz method was observed at every gestational age and was greatest at gestational ages of less than 35 weeks. The physical characteristics of the postnatal assessment were in closer agreement with the best obstetric estimate than the neurological characteristics. These findings concur with other investigations that indicate that the Dubowitz postnatal assessment of gestational age overestimates the gestational age interval from date of LMP in low birthweight and preterm infants. PMID- 1522430 TI - Improving the prediction of surfactant deficiency in very low-birthweight infants with respiratory distress. AB - With the availability of exogenous surfactant therapy, distinguishing between surfactant deficiency and other causes of respiratory distress soon after birth is critical. Of 149 very low-birthweight (VLBW) infants of 24 to 30 weeks' gestation, 107 (72%) had both clinical and radiographic features of respiratory distress syndrome (RDS). Analysis of amniotic fluid obtained within 24 hours before birth or of the initial tracheal aspirate after birth for phosphatidylglycerol (PG) showed that absence of PG had a positive predictive value (PPV) of 80% for predicting RDS, while an immature lecithin/sphingomyelin (L/S) ratio had a PPV of 86% with a 68% specificity. When PG was absent and the L/S ratio was immature, the PPV for RDS increased to 89% (97% specificity). Phospholipid analysis was superior to gestational age alone in predicting RDS (P less than or equal to .02). Receiver operating characteristic (ROC) analysis detected different thresholds for immature L/S ratios for amniotic fluid (2.0) and initial tracheal aspirate (3.0) for predicting RDS. A tracheal aspirate L/S ratio less than or equal to 3.0 predicted RDS with 91% accuracy, while an amniotic fluid L/S ratio less than or equal to 2.0 predicted RDS with 90% accuracy. ROC curve thresholds for either tracheal aspirate or amniotic fluid permit selection of VLBW infants most likely to benefit from surfactant treatment. These analyses improve the accuracy of diagnosing surfactant deficiency-associated RDS using only clinical and radiographic diagnoses, and may permit a more focused approach for rescue surfactant therapy in infants presenting with clinical symptoms of respiratory distress.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1522431 TI - Patterns of illicit drug use at the time of labor in a private and public hospital. AB - The majority of prevalence data on perinatal substance abuse describe low socioeconomic patient populations. This study of illicit drug use at the time of labor was done to identify patterns of drug use in both private and nonprivate patients. Anonymous urine samples were collected from 1000 patients, 500 admitted in labor to a private hospital and 500 admitted to a public hospital. All samples were screened for cocaine, opiates, cannabinoids, and amphetamines. A positive result of screening for any drug was detected in 8.2% of patients. More positive results of screening for any drug were found in nonprivate patients (11.4%) than private patients (5%), with nonprivate patients significantly more likely to test positive for cocaine or cannabinoids or both. Black patients contributed 64.5% of the positive tests for cocaine, significantly more than white (17.6%) or Hispanic patients (17.6%), whereas white patients contributed significantly more positive tests for cannabinoids (85%) than black (5.4%) or Hispanic patients (7.1%). Assessment of patterns of perinatal drug use in communities will support appropriate allocation of resources and targeting of patient and provider education. PMID- 1522432 TI - Reducing the hypoxemia, bradycardia, and apnea associated with suctioning in low birthweight infants. AB - Hypoxemia and bradycardia are major complications associated with suctioning the neonate. Apnea has been reported following caregiving during peak hours of activity in a neonatal intensive care unit (NICU). This study determined the incidence of hypoxemia, bradycardia, and apnea associated with the standard suction protocol used in one NICU. None of the 17 low birthweight infants suctioned between the peak caregiving activity hours of 8 and 11 AM exhibited bradycardia or apnea. Eleven of the 17 infants experienced no hypoxemia. Six infants displayed hypoxemia that lasted for less than 3 minutes. None of the infants exhibited bradycardia or apnea in association with this suction protocol. Patterns of escalating blood pressure noted in this study are worrisome because of the increased risk of intraventricular hemorrhage. PMID- 1522433 TI - Breech management. PMID- 1522434 TI - Reducing neonatal transfusions. AB - In an attempt to prevent blood transfusions from being ordered unnecessarily in our neonatal intensive care unit (NICU), we developed transfusion guidelines and prospectively evaluated their impact on our transfusion practices. Initially, 17% of our packed red blood cell transfusions (PRBCT) did not meet our guidelines. However, 6 months following development of the guidelines, this decreased to 9%, and 12 months later, it decreased to 1%. Although the guidelines are clearly arbitrary, they do provide for consistency within our NICU and a method of evaluating our own use of PRBCT. PMID- 1522435 TI - A timely scenario. Wars in the desert, wars in the ICU. PMID- 1522436 TI - The grief response to mid-trimester fetal loss. AB - This descriptive study examines the grief response of mothers who experienced a fetal loss in the middle trimester of pregnancy. Twenty mothers who lost a baby through spontaneous abortion or perinatal death within 1 year participated in this study. Data were collected by mailed questionnaires. All characteristics typical of the grief response were identified, including despair, anger or hostility, guilt, loss of control, rumination, depersonalization, somatization, and death anxiety. Comparison of the study population to a group of parents who suffered the loss of a child and to a group of women who had suffered the death of a close relative demonstrated that the study group presented a grief response similar in nature and intensity to the two normative groups. This study supports previous studies that indicated the existence of grief after mid-trimester fetal loss. Replication of this study with a larger sample is recommended to further support these findings. PMID- 1522437 TI - The high-risk infant environment. Part 1. The role of the neonatal intensive care unit in the outcome of high-risk infants. PMID- 1522438 TI - The California Diabetes and Pregnancy Program: implementation of a multicenter experience with diabetic pregnancies. AB - The California Diabetes and Pregnancy Program (CDAPP) began in 1984 as a multicenter, collaborative project with support provided by the state Department of Health Services, Maternal and Child Health Branch. Between its inception and 1988, it expanded from three to eight perinatal regions, making the CDAPP model of care available to patients in 19 clinical affiliate sites. The care was provided by a multidisciplinary team composed of physicians, a diabetes educator, a registered dietician, a social worker, and appropriate consultants. The elements of this model of care included comprehensive patient education, active patient participation in care, maternal and perinatal medical assessment, and collection of standardized patient information adequate to allow a programmatic and medical evaluation of the CDAPP. Despite impressive growth of the program by December 1988, statewide implementation of CDAPP is incomplete. PMID- 1522439 TI - Prolonged labor with persistent occiput-posterior position in postterm pregnancy. PMID- 1522440 TI - Perinatal pathology casebook. Twin reversed arterial perfusion (TRAP) sequence. PMID- 1522441 TI - Visual diagnosis casebook. Congenital syphilis. PMID- 1522442 TI - PDA response. FDA proposal to amend cGMP's entitled--use of aseptic processing and terminal sterilization in the preparation of sterile pharmaceuticals for human and veterinary use. Parenteral Drug Association. PMID- 1522443 TI - Variability in the LAL test: comparison of three kinetic methods for the testing of pharmaceutical products. AB - Data presented in this study indicate that there is considerable variability in spike recoveries between three different kinetic LAL methods as used for the testing of a variety of parenteral products. However, successful spike recoveries were observed for each of the thirteen products under test on at least one of the three kinetic methods used, suggesting that problems caused by spike recovery variability may be easily controlled in the laboratory by flexibility in the choice of method. PMID- 1522444 TI - Comparison of different rubber stoppers; the effect of sterilization on the number of particles released. AB - The effect of sterilization on the number of particles released from five different types of rubber stoppers, as well as on their surface roughness and elemental composition before and after sterilization is described. The stoppers were immersed in 200 ml of 0.9% sodium chloride solution in conical flasks. The number of particles released into the sodium chloride solution was measured by Coulter Counter. The surface roughness and the elemental composition of the stoppers were determined by SEM/EDX. All measurements were made both before and after sterilization at 121 degrees C to F0 15 mins. The number of particles released from a stopper during sterilization varies considerably between different stoppers and even between different batches of the same stopper. The only non-siliconized stopper in this study performed well. The absence of surface siliconization may have contributed to this performance. The scanning electron micrographs revealed well the differences in the surface roughness of the stoppers. The sterilization generally increases the surface roughness of the samples. The x-ray microanalysis revealed that the elemental composition of the stoppers may vary not only between different types of stoppers but also between different batches of the same stopper. PMID- 1522445 TI - A review of the U.S. FDA Guideline on Aseptic Processing. PMID- 1522446 TI - Sterile product manufacturing technology. PMID- 1522447 TI - Industry perspective on the validation of column-based separation processes for the purification of proteins. Parenteral Drug Association. AB - Validation of column-based separations is necessary to ensure the quality and safety of protein and peptide products produced by rDNA, peptide synthesis, and hybridoma technologies. Process validation for column-based separations includes qualification of raw materials, equipment, and the purification process. Combined with in-process control and quality control of the final product, column validation ensures that a uniform product is produced consistently from batch to batch. In the best case, validation is designed into the process. During process design, techniques are selected which can remove impurities and contaminants. Equipment and chromatographic media which can perform reproducibly are selected. Column performance standards, cleaning and regeneration routines, and column life should be considered as early as possible. Clearance studies should be planned and implemented to ensure that a product is produced with the requisite purity. There are no explicit rules for process validation of column-based separation processes. This document is intended to serve as a starting point for those needing to validate column-based separation processes. PMID- 1522448 TI - Pre-approval inspection program for drugs. PMID- 1522449 TI - American Pediatric Surgical Association principles of pediatric trauma care. PMID- 1522450 TI - Differences in trauma care among pediatric and nonpediatric trauma centers. AB - To characterize pediatric trauma care, state trauma registry data from all designated trauma centers in Pennsylvania were divided into three categories, that from: (1) pediatric centers, (2) urban nonpediatric centers, (3) and rural nonpediatric centers. From October 1, 1986 through September 30, 1989 (3 years), 4,615 patients less than 15 years old were admitted to 28 trauma centers in Pennsylvania. Nonpediatric centers cared for the majority of children (2,734, 59.2%), but the average number of children treated per nonpediatric institution (105.1 per year) was far fewer than the average treated in the pediatric centers (940.5). Pediatric trauma centers in the state treated a younger population (6.4 +/- 4.2 years, mean +/- SD) compared with urban and rural nonpediatric centers (8.4 +/- 4.2 and 8.1 +/- 4.3 years, respectively; P less than .05). Pediatric centers received proportionately more children by transfer (56.2%), victims of falls (34.6%), pedestrian injuries (16.8%), and head and neck injuries (41.8%, all P less than .05). Nonpediatric centers received children directly from the scene of injury more frequently than transferred from other hospitals. The male:female sex ratio in urban nonpediatric centers was significantly higher (70.1%, P less than .05) than in the other two groups. Rural nonpediatric centers cared for a higher proportion of motor vehicle passengers (28.5%) and patients classified as "other" in the state registry, a category to which bicycle injuries are assigned (28.2%, P less than .05). Mortality was highest in rural nonpediatric centers (6.2%). The death rate in pediatric centers and urban nonpediatric centers were similar (4.1%) and significantly lower (P less than .05).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1522451 TI - Tracheostomy in children with emphasis on home care. AB - Tracheostomy in children is not a benign procedure. Tracheostomy-related mortality rates among children have been previously reported to be as high as 10% to 27%. Children with tracheostomies are especially vulnerable after home discharge with mortality rates of 0.5 to 2 deaths per 100 months at home. In order to assess the impact of extensive parental education and home nursing care on tracheostomy-related mortality, we report our experience over 9 years with 44 children receiving tracheostomies. Each child was maintained at home with a tracheostomy for an average of 19 months for a total of 635 months of home tracheostomy care. Indications for tracheostomy were tracheomalacia (32%), obstructive airway lesions (23%), central nervous system lesions (16%), vocal cord paralysis (9%), Pierre Robin syndrome (9%), and a list of miscellaneous conditions (11%). Our tracheostomy care regimen begins with intensive parental training in tracheostomy management for a minimum of 10 days prior to discharge. Home nursing was arranged for 77% of these children for an average of 11 hours per day at the time of discharge. Eighty-three percent had home apnea monitors. Discharge of these children was delayed or transfer to a secondary hospital was made when parents failed to show adequate proficiency in tracheostomy management with existing home nursing. Eight percent were ventilator dependent at discharge. As of January 1, 1989, 34% of these children have been decannulated. There were six deaths, all due to underlying disease. There were no tracheostomy-related deaths in hospital or after discharge home.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1522452 TI - Treatment of infantile subglottic hemangioma with electrocautery. AB - Laryngeal subglottic hemangioma is a rare but potentially life-threatening congenital lesion that can compromise that infant airway. A multitude of medical and surgical modalities have been used in the treatment of this lesion but no single approach has received universal acceptance. Three infants with subglottic hemangiomas were treated successfully with electrocautery; each was managed without tracheostomy. Bronchoscopic electrocautery appears to be a safe, effective, inexpensive way to manage infantile subglottic hemangioma. PMID- 1522453 TI - Familial pheochromocytomas with unusual associations. AB - Pheochromocytoma occurs in a familial pattern in approximately 10% of patients. Although most familial pheochromocytomas are an expression of the genetic abnormality of neuroectodermal dysplasia or the genetic syndrome of multiple endocrine neoplasia, some familial pheochromocytomas occur without associated disease. Two patients with familial pheochromocytoma are described. One had an extraadrenal tumor, producing severe renal artery stenosis and in whose family pheochromocytomas were found in three successive generations. A second had multiple pheochromocytomas associated with von Hippel-Lindau disease and a family member with multiple endocrine neoplasia type 2. The combinations and permutations of these genetic entities form discrete syndromes, with other peculiar interrelationships, pathologically related to an aberration in the migration, growth, and differentiation of the neural crest cells, and emphasizing their common neuroectodermal origin. The unique features that characterize the familial pheochromocytomas and cause diagnostic and therapeutic challenges are reviewed. PMID- 1522454 TI - Serial measurement of urinary VMA and HVA levels from one infant: a study for neuroblastoma mass screening. AB - Urinary vanillylmandelic acid (VMA), homovanillic acid (HVA), and creatinine in 188 samples from one infant during the ages of 1 to 12 months were measured serially by high-performance liquid chromatography (HPLC). The mean VMA and HVA levels of the total 188 samples in this study were 11.9 +/- 1.39 and 22.9 +/- 2.92 micrograms/mg creatinine with coefficients of variation (CVs) 11.7% and 12.8%, respectively; and of 76 samples from 5 to 12 months of age, 12.3 +/- 0.84 and 23.1 +/- 2.03 micrograms/mg creatinine with CVs 6.8% and 8.8%. The CVs of VMA and HVA levels expressed in microgram per milligram of creatinine had decreased after 6 months of age (VMA, 5.0% to 8.3%, HVA, 5.3% to 8.4%). Chromatograms demonstrated the similar pattern from 1 to 12 months of age, although the infant had been fed foods typical in Japan, which included breast milk, seasonal fruits, vegetables, fish, chicken, and meat. Diurnal fluctuations of VMA and HVA levels in urine were not significant. When HPLC is used for measurement of VMA, HVA, and creatinine, it is not necessary to restrict foods that cause false-positive results in the qualitative VMA test from the infant's diet. Furthermore, random urine samples obtained throughout the 12 months could be effectively used for the measurement of these substances. PMID- 1522456 TI - CT differentiation of benign and malignant lung nodules in children. AB - The superiority of computed tomography (CT) for detection of lung nodules has been documented and attempts have been made to distinguish benign from malignant lesions in adults. We attempted to characterize lung nodules in 12 children with solid malignant tumors (aged 8 months to 17 years) in an effort to differentiate benign from metastatic disease. All scans were performed at 10-mm contiguous intervals on a GE 9800 CT scanner. The scans were retrospectively viewed by two pediatric radiologists independently and without knowledge of the pathological findings. All biopsies were done via open thoracotomy. The CT findings were correlated with pathology results. Twelve children had 13 nodules biopsied. Six of these showed malignancy, two showed inflammatory changes, and two had a reactive subpleural lymph node. In three children, no abnormality was found and a biopsy was not obtained. One child had a metastatic nodule in one lung, and a simultaneous inflammatory nodule in the other. The radiologists agreed with each other on the CT interpretation in 11 of 13 surgically explored areas. They correctly predicted malignancy in four cases and correctly excluded it in two cases. However, they were simultaneously incorrect in five instances. Our conclusion is that, contrary to reports in adults, a tiny nodule may be either benign or malignant. Malignancy cannot be separated from benign disease by CT established criteria. PMID- 1522455 TI - Index of pulmonary expansion: a new method to estimate lung hypoplasia in congenital diaphragmatic hernia. AB - In order to find a simple method for assessing the degree of lung hypoplasia in congenital diaphragmatic hernia (CDH), we measured an index of pulmonary expansion (V/P: expiratory tidal volume over inspiratory pressure) in 23 pulmonary normal and 16 CDH neonates. We also measured V/P in 9 newborn lambs, 6 with experimentally induced CDH and 3 controls, and compared V/P values with fractional lung masses (FLM: lung weight over body weight). In animals, the correlation between V/P and FLM was significant (P less than .05), whereas there was a very significant inverse correlation between pulmonary interstitial emphysema found at postmortem and FLM (P less than .01). These findings suggest that V/P could be an indicator of lung hypoplasia and, therefore, of sensitivity to barotrauma. In neonates with CDH, this index could be useful to make comparisons between series and to separate infants who cannot be ventilated at usual pressures without significant barotrauma. PMID- 1522457 TI - Reflux strictures of the esophagus in children. AB - Although the therapeutic approach to gastroesophageal reflux in children is well established, there are differences of opinion regarding the management of esophageal strictures, viz bougienage with medical therapy, fundoplication without dilatation, preoperative dilatation followed by fundoplication with intraoperative and postoperative dilatation, or resection and interposition. Sixteen consecutive children (mean age, 30.2 months) with reflux strictures were evaluated, constituting 12% of children operated on for gastroesophageal reflux. The strictures became clinically apparent 22.4 months (mean) from the onset of symptoms and were diagnosed by contrast studies and endoscopy. At first endoscopy all the patients had well-established fibrotic strictures. The strictures were mostly situated in the middle or lower esophagus and 7 were longer than 3 cm in length. All 16 were treated with antacids, H2-receptor blockers (Cimetidine), prokinetic agents, and intense nutritional resuscitation, together with preoperative stricture dilatations (average, 3.6 times). This was followed by fundoplication when nutritional parameters had been restored, esophagitis improved, and the strictures dilated to adequate size. Seven children required concomitant gastrostomies for prograde esophageal dilatations. Twelve children needed postoperative esophageal dilatations. The results were satisfactory in 14 (88%). Two required endoesophageal resection for localized unyielding strictures. One child responded only after failed reflux surgery was corrected at a second procedure. During an average follow-up of 8.2 years (range, 3 to 11) there has been no stricture recurrence and growth velocity was restored in all. We conclude that our preferred method is preoperative in-hospital management of gastroesophageal reflux with maximum nutritional support and careful evaluation of the degree and extent of esophagitis and fibrous scarring.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1522458 TI - Isolated blunt liver trauma: is nonoperative treatment justified? AB - During the past 8 years 13 children with isolated blunt liver trauma were managed nonoperatively. All patients selected for this management were hemodynamically stable after initial resuscitation and were without signs of other associated intraabdominal injuries on ultrasonogram and/or computed tomography. Patients were observed in an intensive care unit for at least 48 hours with repeated clinical assessments, laboratory studies, and bed rest. One patient with type 3 injury was operated on 8 days after injury because of sudden intraperitoneal bleeding on ambulation. Five patients required blood transfusions of not more than 300 mL per patient. Laboratory values returned to normal from 7 to 21 days after injury. Resolution of hepatic injury on ultrasonogram took from 1 to 3 months. Complete bed rest was prescribed for at least 10 days depending on the type of injury, with restricted activities up to 3 months postinjury. No complications were seen in this series. PMID- 1522459 TI - Hirschsprung's disease: a possible cause of anastomotic failure following repair of intestinal atresia. AB - Despite several reported cases, the association of Hirschsprung's disease and intestinal atresia is not widely recognized. We describe three patients with jejunoileal atresia who all had a preoperative barium enema that failed to show a transition zone. All three patients developed an anastomotic leak of the atresia repair, and required a temporary diverting enterostomy. Two patients had total colonic Hirschsprung's disease and in one, the transition zone was in the midtransverse colon. Histological examination of the appendix at the time of repair may be helpful in patients with small intestinal atresia. In patients who develop an anastomotic breakdown, rectal biopsy should be performed to rule out Hirschsprung's disease. PMID- 1522460 TI - Anomalous congenital bands causing intestinal obstruction in children. AB - The records of eight patients treated for intestinal obstruction resulting from bands that have no identifiable embryologic or acquired basis were reviewed retrospectively. All patients presented with symptoms and signs indicative of intestinal obstruction. Patients older than 2 years of age additionally had a history of chronic abdominal pain. One thick anomalous congenital band with blood vessels in it was found to be the cause of obstruction in each patient. Bands were located between ascending colon and terminal ileum in four patients (50%), ligament of Treitz and terminal ileum in two patients (25%), right lobe of liver and terminal ileum in one patient (12.5%), and right lobe of liver and ascending colon in one patient (12.5%). The obstructive mechanisms were compression of bowel by band in five patients (62.5%) and entrappment of an intestinal loop between the band and mesenterium in three patients (37.5%). These bands are suggested to be the anomalies of mesenterium that may cause intestinal obstruction and chronic abdominal pain in children. PMID- 1522461 TI - Intussusception: prediction of outcome of gas enema. AB - Gas has replaced barium as the preferred medium for enema reduction of intussusception in tertiary pediatric institutions. Previously, adverse clinical features that in combination predicted a low likelihood of successful reduction using barium had been identified and used to select patients suitable for attempted enema reduction. This study examines whether these adverse features are equally applicable to gas reduction of intussusception. For any given number of adverse features, gas enema reduction was found more likely to be successful than barium reduction and, in the absence of clinical evidence of peritonitis, multiple adverse features probably do not represent a contraindication to attempted gas enema reduction. PMID- 1522462 TI - Acute appendicitis in children with leukemia and other malignancies: still a diagnostic dilemma. AB - Of 6,099 children treated for malignancy, 16 (ages 3.5 to 18 years) developed acute appendicitis between 1962 and 1989. Fourteen had leukemia (ALL 10, AML 4). One each had rhabdomyosarcoma and Ewing's sarcoma. Active malignancy at diagnosis was noted in 10, 4 of whom had severe neutropenia (absolute neutrophil count less than 500/mm3). Of all the leukemics (2,794/6,099), abdominal pain during induction was a frequent complaint. The incidence of appendicitis, however, was low (0.5%). Nine of the 16 patients presented classically, facilitating prompt diagnosis and treatment. Six diagnoses were delayed. Three of these patients presented atypically with vague, nonlocalized pain, abdominal distention, lack of abdominal guarding, fever, dehydration, diarrhea, and unusual symptoms such as upper gastrointestinal bleeding. In each of these 6 patients the appendix was ruptured. Delays led to complications and deaths. Three patients required perioperative transfusions to treat excessive bleeding and two patients with ruptured appendicitis developed wound abscesses. Two patients died; in one, ruptured appendix was diagnosed only at autopsy. The other patient died of uncontrolled sepsis. Typhlitis occurring during induction chemotherapy may present similarly and is the main differential diagnosis. Typhlitis will usually improve with medical treatment alone. Nausea and vomiting (13/16), right lower quadrant pain (13/16), guarding (14/16), tachycardia (12/16), fever (10/16), and rebound tenderness (10/16) were the most frequent signs and symptoms of appendicitis. Persistent localized abdominal pain and guarding, lack of improvement with medical treatment, clinical deterioration, and the development of a mass were our indications for laparotomy. Despite major improvements in therapy, there is still a 37.5% error rate in our ability to accurately diagnose appendicitis in pediatric cancer patients. PMID- 1522463 TI - Complications of surgical significance in pediatric renal transplantation. AB - From 1969 to 1986, 303 renal allografts (290 cadaveric) were placed in 215 pediatric recipients. Twenty-three patients (7.6%) had renovascular complications and 16 (5.3%) had nonrenovascular complications. The overall incidence of surgically significant complications was 12.9%. Of these, 54% were felt to be of a technical etiology. The remainder were surgically significant in that their management necessitated operative intervention. PMID- 1522464 TI - Single-system ectopic ureters: a review of 12 cases. AB - Eight boys and 4 girls with single-system ectopic ureters were seen during a 15 year period. The abnormality was bilateral in 4 patients and the majority had major associated urological and other abnormalities. Eight ectopic ureters were reimplanted successfully into the bladder and 4 nonfunctioning kidneys were removed, as were 2 "blind" ectopic ureters. One patient died during the neonatal period and the others have been followed from 1 to 15 years. Renal function was noted to be normal in 10 patients and 1 has mild renal failure. Bladder function was normal in 8 patients. Early surgery should be undertaken in patients with single-system ectopic ureters. Stabilization of the upper urinary tract can be anticipated and satisfactory bladder function can also be expected in the majority of cases. PMID- 1522465 TI - The ectopic ureterocele: a proposed practical classification based on renal unit jeopardy. AB - A classification system for ectopic ureteroceles based on renal unit jeopardy is presented. This system has been found to be predictive of response to surgical reconstruction and is thus helpful in selecting the initial reconstructive approach. Specific guidelines for the selection of an appropriate surgical strategy are provided. PMID- 1522466 TI - Evolution in the management of infant pyeloplasty. AB - Improving diagnostic modalities, evolving concepts regarding perinatal renal physiology, and advances in surgical technique have contributed to an evolution in the management of infant pyeloplasties. Currently, the majority of patients present with a prenatal diagnosis of ureteropelvic junction obstruction and do not require surgical intervention prior to 4 weeks of age. Postnatal ultrasound, voiding cystourethrography, and nuclear renography complete the diagnostic evaluation, with intravenous urography and retrograde pyelography being unnecessary in the majority of infants. A decreasing incidence of complications and a shortening of hospital stay has been documented. We presently prefer a dismembered, nonintubated technique performed through a dorsal lumbotomy approach. PMID- 1522467 TI - Intraoperative assessment of blood flow to strangulated stomach by pulse oximetry. AB - A pulse oximeter was used to detect safe margins for resection of a strangulated stomach. The sensor probe was placed intraoperatively on various portions of the stomach, which herniated through a left lateral diaphragmatic defect. Failure to detect blood flow by this device in equivocally compromised tissue helped in the assessment of safe viable margins for resection. PMID- 1522468 TI - Transcatheter embolization of a high-flow congenital intrahepatic arterial-portal venous malformation in an infant. AB - An intrahepatic arterial-portal venous malformation (APVM) was diagnosed in a 4 1/2-month-old infant with portal hypertension. Visceral angiography showed a large saccular vascular space in the left hepatic lobe with a multiplicity of feeding arteries and drainage into the left portal vein. The lesion was successfully treated by transcatheter embolization following two unsuccessful surgical procedures. Two years later portal vein thrombosis with cavernous transformation was diagnosed, possibly a consequence of the high-flow arterial portal shunt and its subsequent occlusion. Knowledge of the anatomic differences between this rare congenital APVM and the more commonly occurring arterial-portal fistula is crucial in planning effective transcatheter embolotherapy or surgery for these lesions. PMID- 1522469 TI - Gastroduodenal duplication. AB - A newborn baby presented with a lump in the right hypochondrium. She had a bout of upper gastrointestinal bleeding. At operation, a pyloroduedenal duplication cyst was successfully removed. The relevant literature is reviewed. PMID- 1522470 TI - Intestinal trichobezoar with perforation in a child. AB - A 4-year-old girl presented with a history and examination results suggestive of peritonitis. Exploration of abdomen was done with suspicion of enteric perforation, which showed long ileal trichobezoar with perforation of .5-cm diameter. The stomach was devoid to any fragment of bezoar. There was no history of hair eating and nervous habits. PMID- 1522471 TI - Renal trauma with posttraumatic hypertension in a neonate. PMID- 1522472 TI - Nonsurgical therapy of splenic rupture in a hemophiliac. AB - A boy with known hemophilia A sustained severe blunt abdominal trauma that caused major splenic rupture and hypovolemia. The administration of blood and aggressive clotting factor replacement therapy stabilized his course and he was successfully managed without resorting to operation. PMID- 1522473 TI - An unusual case of pelviureteric junction obstruction. AB - We describe an unusual case of pelviureteric junction obstruction in a child due to a benign ureteric polyp. Benign neoplasms of the ureter are uncommon in adults and extremely rare in children. PMID- 1522474 TI - Augmented venous access in the problematic ECMO patient: a case report. AB - Extracorporeal membrane oxygenation (ECMO) provides an adjunct to support of neonates with respiratory distress. The rate of venous drainage is the limiting step to the amount of arterial flow that may be generated during ECMO. We present a 3-kg, 37-week gestation female with congenital diaphragmatic hernia (CDH) whose anatomic venous drainage was insufficient to allow total extracorporeal support. The internal jugular vein was of insufficient size to allow placement of a cannula large enough to support adequate bypass flow. We established minimally acceptable flow by simultaneous caudad and cephalad catheterization of the internal vein. We performed a right lower quadrant retroperitoneal dissection and cannulated the common iliac vein when systemic pressures deteriorated at 24 hours with marginal venous drainage. After triple cannulation the bypass flows were normal. The right leg developed mild cyanosis and edema immediately following cannulation, but these changes resolved over 24 hours with elevation. The common iliac vein provides a desirable route for augmentation of venous drainage in the patient with difficult standard, or cephalad, jugular venous access for extracorporeal support. PMID- 1522475 TI - Conservative management of splenic injury in infectious mononucleosis. AB - Splenic rupture, in association with mononucleosis, can be lethal. Most reported cases of splenic rupture in patients with mononucleosis have not responded to conservative splenic preserving measures and have resulted in splenectomy. We report a case of traumatic splenic disruption in a patient with mononucleosis in whom conservative management was successful. We recommend consideration of splenic preservation measures in patients with mononucleosis and splenic disruption, if the patient is stable and meets other criteria of conservative management. PMID- 1522476 TI - Effective early treatment of hepatic venoocclusive disease with a central splenorenal shunt in an infant. AB - Venoocclusive disease of the liver (VOD) is a well-described complication following chemotherapy. It is manifested by jaundice and signs of portal hypertension and carries a mortality rate approaching 50%. There is no known treatment for the disease itself, although several recent reports suggest portacaval diversion may be effective in treating its sequelae. A 6.75-kg 8-month old boy with VOD following bone marrow ablation and bone marrow transplantation (BMT) for juvenile chronic myelogenous leukemia (JCML) is presented. Over a 6 week period following bone marrow ablation he developed ascites refractory to diuretics, jaundice, and hematemasis with normal hepatocellular function. Splenectomy with a central splenorenal shunt was performed, which resulted in a significant reduction in portal pressures and complete resolution of his ascites and hematemasis without resultant encephalopathy. We propose that central end-to side splenorenal shunting is an acceptable treatment for portal hypertension due to VOD and can be successfully performed in infants. PMID- 1522477 TI - Biliary atresia and the polysplenia syndrome. PMID- 1522478 TI - Felix Wurtz. PMID- 1522479 TI - Optimum numerical integration methods for estimation of area-under-the-curve (AUC) and area-under-the-moment-curve (AUMC). AB - Eleven numerical methods for estimation of AUC (including 4 new methods) and 22 methods for AUMC (including 8 new methods) were tested on large simulated noisy datasets representing bolus, oral and infusion concentration-time profiles. Some methods were unacceptable because their mean error was large; these included a commonly recommended form of the linear trapezoidal rule for AUMC. Others, notably Lagrange and cubic spline methods, were unacceptable because the variance of their estimates was large. These methods should be abandoned. A simple and easily programmed new method, parabolas-through-the-origin then log-trapezoidal rule, performed especially well. PMID- 1522480 TI - Dynamics of drug distribution. I. Role of the second and third curve moments. AB - Conventionally, the dynamics of distribution in the body is evaluated by the so called distribution half-life (e.g., t1/2, alpha); but then the mean time of the distribution process is underestimated due to the influence of elimination. By contrast, information about the dynamics of distribution contained in drug disposition curves can be extracted by the second and third curve moments, parameters that are related to the variance (VDRT) and skewness (SDRT) of residence time distributions; whereas the equilibrium state characterized by the volume of distribution (Vss), is determined by the mean residence time (MDRT) or the first curve moment. The approach represents a general noncompartmental analysis that is independent of a detailed structural model or a particular disposition function. Two parameters are introduced to characterize the dynamics of drug distribution: (i) the degree of departure of the system from "well-mixed" behavior of instantaneous distribution equilibrium (related to VDRT) and (ii) the mean time until equilibration is achieved (mean equilibration time, MEQT), which additionally depends on SDRT. Both parameters are quantitative measures of the dynamics of distribution and display explicit physical significance in terms of distribution within the corresponding noneliminating system. It is further shown that the so-called "distribution phase" in biexponential disposition curves is related to a monoexponential mixing curve of its corresponding noneliminating system with an equilibration or mixing half-time, t1/2,M = t1/2,alpha (V beta/Vss*), where Vss* denotes the distribution volume of the noneliminating system. The results are applied to mixing and disposition curves measured for acetaminophen in liver-ligated and intact rats, respectively. PMID- 1522481 TI - A computationally efficient approach for the design of population pharmacokinetic studies. AB - A computationally efficient procedure was devised for designing experiments in which population pharmacokinetic parameters are estimated. The method, referred to as the large-sample approach, evaluates the variances of parameter estimates for a population pharmacostatistical model. The procedure utilizes the NONMEM program and requires a single simulation that assumes many, say 1000, subjects. The approach reduced CPU time by about a factor of 50 when compared with the evaluation of the same variances by the direct simulation of experiments. The large-sample and simulation approaches yielded generally similar values for the variances of parameter estimates. The variances calculated by the large-sample approach were, in the case of a simple model, close to the expected variances. The proposed method identified correctly the imprecise parameter estimates but somewhat underestimated their variances. PMID- 1522482 TI - Evaluation of hypothesis testing for comparing two populations using NONMEM analysis. AB - In a simulation study of inference on population pharmacokinetic parameters, two methods of performing tests of hypotheses comparing two populations using NONMEM were evaluated. These two methods are the test based upon 95% confidence intervals and the likelihood ratio test. Data were simulated according to a monoexponential model and, in that context, power curves for each test were generated for (i) the ratio of mean clearance and (ii) the ratio of the population standard deviations of clearance. To generate the power curves, a range of these parameters was employed; other pharmacokinetic parameters were selected to reflect the variability typically present in a Phase II clinical trial. For tests comparing the means, the confidence interval tests had approximately the same power as the likelihood ratio tests and were consistently more faithful to the nominal level of significance. For comparison of the standard deviations, and when the volume of information available was relatively small, however, the likelihood ratio test was more able to detect differences between the two groups. These results were then compared to results on parameter estimation in order to gain insight into the question of power. As an example, the nonnormality of estimates of the ratio of standard deviations plays an important role in explaining the low power for the confidence interval tests. We conclude that, except for the situation of modeling standard deviations with only sparse information, NONMEM produces tests of significance that are effective at detecting clinically significant differences between two populations. PMID- 1522483 TI - Pharmacokinetic model for subcutaneous absorption of cyclosporine in the rabbit during chronic treatment. AB - The objective of this study was to examine the concentrations in blood of cyclosporine (CyA) in rabbits during chronic subcutaneous (sc) administration and to propose a model that describes these data. Ten rabbits received sc CyA at 15 mg/kg daily for 1 week, then at 20 mg/kg twice weekly for 3 weeks, and at 15 mg/kg twice weekly for 7 weeks. Concentrations in blood were obtained weekly during the dosing period, and three to five concentrations were obtained over a 5 week period after dosing was terminated. CyA blood concentration-time (concentration in blood versus time) profiles could not be adequately described by absorption from a single dosing compartment. A two-compartment, sc absorption site model was postulated. Steady-state concentrations in blood from three additional rabbits that had received CyA at 16.8 micrograms/min as a constant rate intravenous infusion were added to the data set. A nonlinear mixed effects model was used to obtain the following parameter estimates (percent relative standard error): K12 = 0.111 day-1 (10.0), k21 = 0.0109 day-1 (12.6), ka = 0.0807 day-1 (11.8), CL/F = 14.6 L/day/kg (3.8), and Vd/F = 1.52 L/kg (13.4), where k12 and k21 are intercompartmental rate constants between sc compartments, ka is the absorption rate constant into the sampling compartment, CL/F is the apparent blood clearance of CyA from the body (F is bioavailability), and Vd/F is the apparent volume of distribution of CyA. The interindividual variability in CL/F was estimated as 20.5% (41.2), and the residual variability was 25.8% (15.6). The sc administration of CyA appears to provide slow, but very significant, absorption in rabbits. PMID- 1522484 TI - A critical evaluation of the present status of toxicity of aminoxyl radicals. AB - The literature on the toxicity of aminoxyl radicals was critically reviewed. It was concluded that, in general, the aminoxyl radicals possess a very low toxicity and are not mutagenic. In support of this contention, several aminoxyl radicals were evaluated in vitro. Thus, aminoxyl radicals 3-carboxy-2,2,5,5 tetramethylpyrroline-1-oxyl (1), 3-carboxy-2,2,5,5-tetramethylpyrrolidine-1-oxyl (PCA; 2), 4-hydroxy-2,2,6,6-tetramethylpiperidine-1-oxyl (Tempol;3), and N-(1 hydroxymethyl-2,3-dihydroxypropyl)-3-carboxyamino-2,2,5,5- tetramethylpyrrolidine 1-oxyl (NAT; 4) were evaluated using Salmonella typhimurium tester strains TA 102 and TA 104, with a supplement of xanthine oxidase enzyme. 1, 2, and 4 were found to be nonmutagenic, while 3 elicited in TA 104 only about a twofold increase in the number of revertants above the control. This response is considered to be, at best, marginal in view of wide fluctuations of experimental scores. The results of the present study are in agreement with those of other studies confirming the nonmutagenicity of aminoxyl radicals investigated to date. However, these conclusions are different from those of a study where 3 was tested in the presence of a generated toxic oxygen species that can cause mutagenic changes of the environment. PMID- 1522485 TI - Influence of higher rates of agitation on release patterns of immediate-release drug products. AB - The dissolution procedure serves as a quality control test to assure batch-to batch uniformity and bioequivalence of a product once the bioavailability of the product has been established. It can also be used to detect manufacturing and/or process variations that could reduce product bioavailability. Dissolution testing must be conducted at an appropriate agitation rate. Tests conducted at high agitation rates may lose the ability to differentiate between good and bad products. Although the effect of high agitation rates has been known for some time, several immediate-release drug products still have United States Pharmacopeia (USP) monograph dissolution procedures that require very high agitation rates. A systematic survey was conducted on marketed tablets of chloroquine phosphate, griseofulvin, hydroxychloroquine sulfate, isocarboxazide, primaquine phosphate, and sulfadiazine. Each of these products has a USP monograph requiring a dissolution test at a paddle speed of 100 rpm. To study the influence of agitation rate on the dissolution rate of these products, dissolution studies were conducted at paddle speeds of 50, 75, and 100 rpm with the USP apparatus 2 (paddle method). The dissolution rate increased with an increase in the agitation rate from 50 to 75 rpm. However, no significant increase in the dissolution rate was noted with an increase in the agitation rate from 75 to 100 rpm. The data support the position that the higher agitation rate of 100 rpm is not necessary for a quality control procedure or a compendial standard for the products tested. PMID- 1522486 TI - Quantitative prediction of transdermal iontophoretic delivery of arbutamine in humans with the in vitro isolated perfused porcine skin flap. AB - The use of the isolated perfused porcine skin flap (IPPSF), an alternative in vitro animal model, to predict the profile of the concentration of arbutamine in plasma samples from humans after transdermal iontophoretic administration of this novel catecholamine is described. The strategy involved administering the drug in the IPPSF (n = 8) and assaying concentrations of drug in the venous efflux versus time (IPPSF venous efflux profile). Intravenous infusion (n = 7) and transdermal studies (n = 32) were also conducted in humans. The IPPSF profile was then used as an input into an intravenous pharmacokinetic model obtained from the human experiments to predict the profile of concentration of drug in plasma versus time (plasma concentration-time profile) seen after iontophoretic administration. The IPPSF profiles were denormalized according to the parameters used in the human studies (i.e., multiplied by in vivo concentration, electrode area, current, and dosing time). For two different sets of iontophoretic dosing conditions, the concentration-time profiles that were predicted on the basis of the IPPSF study were compared with those seen after delivery to humans. PMID- 1522487 TI - Hydroxypropylcyclodextrins in parenteral use. I: Lipid dissolution and effects on lipid transfers in vitro. AB - Hydroxypropyl ethers of cyclodextrins form water-soluble inclusion complexes with lipids. Of the three hydroxypropylcyclodextrins examined, hydroxypropyl-alpha cyclodextrin had limited specificity for phospholipids, and hydroxypropyl-beta cyclodextrin had limited specificity for cholesterol, and hydroxypropyl-gamma cyclodextrin was nonspecific. The formation of inclusion complexes was found to be a fast and reversible process in which complexation of cholesterol did not inhibit its oxidation by cholesterol oxidase, and cholesterol of the erythrocyte membrane could be exchanged within a minute for cholesteryl methyl ether which was in the inclusion complex. Thus, hydroxypropylcyclodextrin in the circulation may catalyze the transport of lipids in the direction of equilibrium distribution. PMID- 1522488 TI - Hydroxypropylcyclodextrins in parenteral use. II: Effects on transport and disposition of lipids in rabbit and humans. AB - Hydroxypropyl ethers of cyclodextrins, after parenteral administration, come into contact with lipids in tissues and in circulation and form water-soluble inclusion complexes with these lipids. A single intravenous administration of hydroxypropyl-beta-cyclodextrin to a hereditary hyperlipidemic Watanabe rabbit slightly and temporarily decreased the level of total cholesterol in serum. Single injections of hydroxypropyl-alpha-cyclodextrin and of the corresponding gamma-homologue, both of which are less potent solubilizers of cholesterol, had lesser effects. Repeated administration of hydroxypropyl-beta-cyclodextrin to rabbits led to a gradual increase in total cholesterol in circulation and eventually to a slight relief of atherosclerotic lesions in the thoracic aorta. The only untoward effects of repeated treatments (total doses of up to 40 g/kg) were vacuoles in cells of proximal convoluted tubules in the kidneys. Repeated administration also strongly increased cholesterol in urine, probably because of excretion of the soluble cholesterol-hydroxypropyl-beta-cyclodextrin complex. Proteins in urine increased significantly, whereas triglycerides increased only moderately after repeated administrations. Intravenous infusion of hydroxypropyl beta-cyclodextrin into a patient with hypervitaminosis A led to a release of liver-stored retinoids into serum in quantities much higher than those that could be directly solubilized by hydroxypropyl-beta-cyclodextrin. Levels of total cholesterol in the circulation of this patient decreased during the infusion. Thus, hydroxypropylcyclodextrins may serve as artificial lipid carriers in the circulation, and because the exchanges that involve inclusion complexation occur very quickly, the presence of hydroxypropylcyclodextrins in organisms may catalytically augment the establishment of equilibria in lipid distribution. PMID- 1522489 TI - Concanavalin A microspheres for a self-regulating insulin delivery system. AB - A self-regulating insulin delivery system based on the competitive binding of glucose and p-succinylamidophenyl-alpha-D-glycopyranoside-insulin (SAPG-insulin) to crosslinked concanavalin A (Con A) microspheres (MSs) has been investigated. Con A MSs prepared by a water-in-oil emulsion technique demonstrated properties of binding to glucose and SAPG-insulin (binding constants of 1.25 x 10(3) and 1.28 x 10(4) M-1, respectively) that are similar to the literature values of these properties for unmodified Con A. The retained binding capacity (number of binding sites per molecule) of Con A MSs, produced with 20% of the epsilon-amino groups crosslinked, was approximately 28% that of intact Con A. As a new device, Con A MSs loaded with SAPG-insulin was enclosed in a heat-sealed, surface modified, porous poly(vinylidene difluoride) membrane pouch. This system showed a pulsatile release pattern for insulin with a short lag time in response to glucose challenges of 50-500 mg/dL. The pattern of release of SAPG-insulin from the devices was studied with varying design parameters, such as surface area, membrane pore size, and loading content of SAPG-insulin. PMID- 1522490 TI - Preparation and evaluation of Eudragit gels. III: Rectal gel preparations for sustained release of pentoxifylline. AB - A novel method was established for the preparation of Eudragit S, Eudragit L, and Eudispert high-viscosity (hv) hydrogel and xerogel preparations containing a medicinal component such as pentoxifylline (an agent that improves cerebral microcirculation). A significant correlation was found between the in vitro mean dissolution time and the in vivo mean residence time of pentoxifylline after rectal administration of these preparations in rabbits. Staying properties of the hydrogel and xerogel preparations in the lower part of the rectum were compared with those of polyethylene glycol 2000 and Witepsol S-55 suppositories in rats, with water-insoluble dye. Eudispert hv hydrogel and xerogel preparations have excellent staying properties in the rectum. The efficacy of Eudispert hv xerogel preparations may be reduced by first passage through the liver after oral administration. PMID- 1522491 TI - Comparative bioavailability of a sustained-release ion-exchange hydralazine product with a potassium (cation) challenge. AB - A sustained-release formulation of hydralazine was manufactured by binding hydralazine to an ion-exchange resin and coating the drug-resin complex with a semipermeable membrane. Because the sustained-release characteristics are due in part to displacement of drug from the drug-resin complex by gastrointestinal ions, the stability of the sustained-release formulation could be compromised if challenged by a high concentration of ions. In this study, 12 healthy male volunteers participated in a two-way crossover trial that was designed to test the bioavailability and release of drug from the sustained-release formulation both with and without concomitant ingestion of a solution of KCl. Blood samples were collected over a 14-h period after administration of either treatment. Analysis of whole blood for hydralazine and comparison of the values of the area under the curve of the concentration of hydralazine versus time, the maximum concentration of hydralazine, and the time to reach the maximum concentration between the two experimental groups showed that KCl had no influence on the bioavailability or release characteristics of hydralazine from the sustained release formulation. PMID- 1522492 TI - Interaction of opiate molecules with lipid monolayers and liposomes. AB - The interaction of opiate molecules (buprenorphine, codeine, dextromethorphan, diprenorphine, etorphine, meperidine, methadone, morphine, and naloxone) with lipids (phosphatidylcholine, phosphatidylinositol, phatidylinositol, phosphatidylserine, and cholesterol) by using liposomes and monomolecular layers as membrane models is described. The ability of opiates to induce leakage of carboxyfluorescin from liposomes is highly dependent on the hydrophobicity of the opiate molecules. Buprenorphine and etorphine increased the membrane permeability in all the experiments. On the contrary, naloxone, morphine, and codeine only caused a slight release of the entrapped dye in the presence of acidic phospholipids. Moreover, the leakage of carboxyfluorescein is directly related to the concentration of drug in the incubation media. Studies of the kinetics of the surface penetration of these molecules into monolayers of phospholipids were performed. Again, in this system, buprenorphine and etorphine exhibited stronger interactions than the most hydrophilic opiates. Nevertheless, in these experiments, differences among the opiate molecules are not so high as in the liposomes. The time course of the penetration of all of these molecules in the monolayers fits the Lineweaver-Burk equation. This fact suggests a lack of specific interactions and the predominance of hydrophobic factors. Moreover, the high percentage of release of entrapped dye caused by some opiate molecules suggests a possible toxic side-effect for these agents. PMID- 1522493 TI - Novel approach to estimate quality of binary random powder mixtures: samples of constant volume. I: Derivation of equation. AB - An equation of the quality of binary random mixtures that applies to powder samples of constant bulk volume was derived from the binomial distribution. In contrast to the Stange-Poole equation for samples of constant mass, this approach can also be used for constituents with large differences in particle size and in bulk density. The validity of this equation was verified with tablets directly compressed from mixtures composed of equal mass proportions of sucrose [volume weighted/volume-number mean diameter (dv), 504 microns] as the coarse ingredient (A) and of a microcrystalline cellulose (Avicel PH 101)-talc mixture (dv, 60 microns) as the fine constituent (B). Because of the difference in the bulk densities of A and B, the equation estimated a coefficient of the random content variation, which for A was double that for B. The content variations found with the tablets were in excellent agreement with the calculated values and reflected the differences predicted from theory. The Stange-Poole equation yielded identical values of the content variations of A and B, which is in contrast to the experimental results. PMID- 1522494 TI - Quinidine as a muscarinic antagonist: a structural approach. AB - The synthesis, spectroscopic characteristics, and single-crystal X-ray structural analysis of quitenidine methyl ester monohydrate, a derivative of the muscarinic antagonist quinidine, are presented. Quitenidine methyl ester monohydrate (C20H24N2O4.H2O) crystallizes in the orthorhombic space group P2(1)2(1)2(1), with a = 16.69(3) A, b = 12.46(2) A, c = 9.70(1) A, and Z = 4. The crystal structure was refined to a discrepancy factor (R) of 0.097. Substitution of the quinidine vinyl chain with a carboxymethyl group does not influence the conformation. The carboxymethyl group is positionally disordered, a fact that complicates refinement of the structure. The water molecule is bonded to the quinuclidine nitrogen atom, and the hydroxyl group forms an intermolecular hydrogen bond with the quinoline nitrogen atom. The molecular structure of the ester was compared with those of quinidine, quinine, and four other antimuscarinic agents. An approximately linear relationship between the distance from the nonaromatic nitrogen to the plane of the aromatic part of the molecules and the blocking potency of these agents was noted; the greater this distance, the more potent is the antagonist. PMID- 1522495 TI - Acid-base properties of pristinamycin IA and related compounds. AB - The pKa values of acid-base equilibria involved in the protonation of pristinamycin IA and its model compound, N-isobutyl-3-hydroxypicolinamide, were determined by UV-visible absorption spectrometry and potentiometric titration. The equilibrium between dipolar ionic and uncharged neutral forms was investigated spectrometrically in methanol-water solutions. With pristinamycin IA, the dipolar ionic form predominated in aqueous solutions buffered to the isoelectric pH. The effects of structure on the ionization constants are briefly discussed. PMID- 1522496 TI - External-standard high-performance liquid chromatographic method for quantitative determination of furosemide in plasma by using solid-phase extraction and on-line elution. AB - A rapid and simple external-standard high-performance liquid chromatographic (HPLC) method has been developed for the determination of the concentration of furosemide in plasma. The analyte is extracted with a C-2 ethyl sorbent. On-line elution of the analyte into the HPLC system is accomplished with an advanced automated sample processor (Varian). Furosemide is quantified by fluorescence detection within a linear range of 25 to 1000 ng/mL (average correlation coefficient, 0.9998), with a limit of detection of 1.8 ng/mL. Both internal- and external-standard procedures were evaluated, and the external-standard procedure demonstrated superior characteristics. The external-standard procedure was precise to within a relative standard deviation of 8% and accurate with less than 3% error throughout the concentration range studied. The external-standard HPLC method was used to analyze the concentration of furosemide in greater than 1000 plasma samples obtained from patients with either normal kidney function or renal failure who had received furosemide either orally or intravenously in an experimental setting. PMID- 1522497 TI - Isolation and solid-state characteristics of a new crystal form of indomethacin. AB - A new polymorphic crystal form of indomethacin was precipitated from an aqueous solution of indomethacin and beta-cyclodextrin by titration with a 0.5 N HCl aqueous solution. Three polymorphs (alpha, beta, and gamma forms) and a new crystal form were differentiated with thermal analysis, infrared spectroscopy, powder X-ray diffractometry, thin-layer chromatography, elemental analysis, and Fourier transform infrared (FTIR) spectroscopy with a newly developed FTIR microscope equipped with a thermal analyzer. The new crystal polymorph of indomethacin exhibited endo- and exothermic peaks near 102.8 and 104.1 degrees C, respectively, because of phase transitions without weight loss, followed by two additional endothermic peaks at 151 and 158.9 degrees C, because of fusion. The differential scanning calorimetry-FTIR system can be used to examine the correlation between structural change of C = O stretching bands of this new polymorph and its thermal response. The new crystal form contained some gamma form crystals, determined with an FTIR microscope equipped with a mapping option. Solid-state carbon-13 nuclear magnetic resonance spectra of the polymorphs of indomethacin were also examined. PMID- 1522498 TI - High-performance liquid chromatographic determination of the pi values of azol-N yl substituents. AB - The pi (hydrophobic constant) values for 16 parent azoles (pyrrole, imidazole, pyrazole, four triazoles, two tetrazoles, indole, benzimidazole, 1H- and 2H indazoles, 1H- and 2H-benzotriazoles, and carbazole) were calculated from the logarithms of the capacity factors (log k') determined by HPLC. The values thus obtained are discussed according to an additive model in which the number and position of pyridinelike nitrogen atoms and the annelation effect are considered. PMID- 1522499 TI - Synthesis and inotropic activity of pyrazolo[4,3-c]pyridine-4-ones and related compounds. AB - Two series of 3,6-dimethyl-1-phenyl-1H-pyrazolo[4,3-c] pyridine-4-ones (5-9) and 3,6-dimethyl-1-phenyl-1H-pyrazolo[4,3-c] pyridine-4-thiones (11-13) were prepared from dehydroacetic acid as starting material and evaluated for positive inotropic activity in vitro. Moreover, the activity of the synthesized compounds was compared with that of mirlinone as a reference. Among these compounds, the positive inotropic activity of 8a, 11a, and 12 were approximately 1.24, 1.77, and 1.11 times more potent, respectively, than that of mirlinone. PMID- 1522500 TI - Degradation kinetics and mechanisms of moricizine hydrochloride in acidic medium. AB - The degradation kinetics of moricizine hydrochloride (1) were examined over a pH range of 0.6 to 6.0 at an ionic strength of 0.3 and 60 degrees C. The disappearance of intact 1 was followed by a stability-indicating HPLC assay. The degradation products, which had approximate solubilities of less than 100 micrograms/mL, precipitated in aqueous solution. The precipitate was collected for HPLC analysis and identification of degradation products. Degradation of 1 was catalyzed by acetate and phosphate buffers and was pH dependent, with the pH of the minimum rate constant located between 2.8 and 3.2. At pH 0.6-2.0, 1 degraded via amide hydrolysis to yield first ethyl (10H-phenothiazin-2-yl) carbamate (2), an amide hydrolysis product, which further oxidized in parallel to give ethyl (3-oxo-3H-phenothiazin-2-yl) carbamate (3), ethyl (10H-phenothiazin-2 yl) carbamate S-oxide (4), and diethyl (3,10'-bi-10H-phenothiazine-2,2' diyl)bis(carbamate) (5), the dimer of the amide hydrolysis product. At pH 2.2 6.0, 1 degraded via a reverse Mannich reaction, to form the reverse Mannich product ethyl [10-(1-oxo-2-propenyl)-10H-phenothiazin-2-yl] carbamate (6), and by parallel reaction via the described amide hydrolysis pathway. The dimer of the amide hydrolysis product was not detectable at pH greater than 2.8. At pH greater than 4.0, the reverse Mannich product was the predominant degradation product. Degradation of 1 was subject to positive and negative kinetic salt effects at pH 1.0 and 4.0, respectively. Arrhenius plots determined at pH 1.0 and 6.0 were linear between 37 and 70 degrees C.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1522501 TI - Evaluation of thermodynamic ionization constants by computation of spectrophotometric and potentiometric experimental data obtained simultaneously from a flow system. AB - A method is proposed for the direct and simultaneous determination of the thermodynamic ionization constants of bifunctional substances, with (microscopic) and without overlap in the ionizations, with computational treatment of spectrophotometric and potentiometric experimental data obtained simultaneously in a flow system. For monofunctional substances, potentiometric data are enough. The data are obtained at very low values of ionic strength, which is variable throughout the experiment because no inert electrolyte is added. The MICROTER program, written in FORTRAN 77, is based on an algorithm of mathematical optimization with a controlled-descent movement. The ionization constants of the following substances of pharmacological interest were determined: cysteine, penicillamine, ofloxacin, and norfloxacin (bifunctional with overlap); cephalexin and cephapirin (bifunctional without overlap); and tolazoline, naphazoline, and oximetazoline (monofunctional). PMID- 1522502 TI - Characterization of a synthetic peptide impurity by fast-atom bombardment-tandem mass spectrometry and gas chromatography-mass spectrometry. AB - Fast-atom bombardment-tandem mass spectrometry (FAB-MS-MS) was used to characterize the structure of atosiban, a synthetic oxytocin antagonist, and one of its synthesis-related impurities. The nature of the structural modification in the impurity of interest, replacement of the proline residue by 5-aminovaleric acid, was determined directly from its product ion MS-MS spectrum. Confirmation of the identity of the impurity was accomplished with GC-MS. PMID- 1522503 TI - Pharmacokinetic implications of changing blood flow in skin. PMID- 1522504 TI - Structure-permeability relationships in percutaneous penetration. PMID- 1522505 TI - Flows of liquid and electrical current through monolayers of cultured bovine arterial endothelium. AB - 1. Monolayers of arterial endothelium on porous membranes were exposed to a constant pressure between 15 and 35 cmH2O. The rates of liquid flow per unit area (Jv/A) through the monolayers were monitored, together with the electrical resistance (Rm) of the endothelium. 2. At constant pressure, Jv/A decreased with an approximately exponential time course, towards a stable baseline value. This behaviour resembles the sealing previously described for cultured vascular endothelium. At 30-35 cmH2O and 37 degrees C, the mean (+/- S.E.M.) half-time (t1/2) of the decrease in Jv/A (the sealing t1/2) was 548 +/- 141 S (n = 5). The difference between the initial and baseline values of Jv/A was expressed as a fraction of the initial value. The mean (+/- S.E.M.) of this sealing fraction was 0.64 +/- 0.03 (n = 5). Mean (+/- S.E.M.) hydraulic permeability (Lp) was 23.9 +/- 6.4 x 10(-7) cm S-1 cmH2O-1 (n = 9), when measured after sealing. Endothelium appeared damaged after sealing at 30-35 cmH2O and 37 degrees C. 3. Sealing was also observed using glutaraldehyde-fixed endothelium at 30-33 cmH2O and 26-28 degrees C. There was no significant difference between the mean sealing t1/2 of these fixed monolayers, and that of unfixed endothelium at 30-35 cmH2O and 37 degrees C. However, mean sealing fraction was significantly larger for the fixed monolayers than for unfixed endothelium at 30-35 cmH2O and 37 degrees C. There were no significant difference between the post-sealing Lps of these fixed and unfixed monolayers, although the fixed monolayers appeared undamaged after sealing. 4. For unfixed endothelium, Rm was lower after sealing at 30-35 cmH2O and 37 degrees C than before pressure application. There was no significant difference between endothelial Rm before and after sealing, for glutaraldehyde fixed monolayers. 5. Sealing was also observed at 0 degree C, using unfixed endothelium at 30 cmH2O. Mean sealing t1/2 was not significantly different from that of unfixed endothelium at 30 cmH2O and 37 degrees C. However, mean sealing fraction was significantly smaller at 0 degree C than at 37 degrees C. Unfixed endothelium appeared undamaged after sealing at 30 cmH2O and 0 degree C. Despite this, the post-sealing Lp was not significantly different from that of unfixed endothelium sealed at 30 cmH2O and 37 degrees C, after allowance was made for the effect of temperature on Lp. Rm was not measured in these experiments. 6. It is proposed that sealing is due to pressure-induced deformation of monolayers.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1522507 TI - Factors affecting movement of excitatory substances from pulmonary capillaries to type J receptors of anaesthetized cats. AB - 1. Using phenyl diguanide (PDG) as an excitatory substance, the role of certain factors that could influence the movement of such substances across the pulmonary capillaries to the J receptors was studied in cats anaesthetized with sodium pentobarbitone. This was aided by using a new method for estimating continuously in vivo the concentration (C) of PDG in the blood of the pulmonary artery. 2. Reduction of pulmonary blood flow by partial occlusion of the inferior vena cava enhanced the responses of the J receptors to PDG significantly in twelve out of thirteen trials. These effects, which occurred at a time when pulmonary capillary pressure (PCP) had fallen, could be related to the increase in the estimated mean C of PDG over the first 3 s or to the C t (concentration x time) area to 50% of peak C. The responses bore no relation to peak C or rate of rise of C. 3. The responses of the receptors to PDG increased significantly after three out of eight injections of PDG while the PCP was raised by partial occlusion of the mitral orifice; reduced responses were recorded after two injections. These results, showing relatively much weaker stimulation by PDG in spite of the enhanced level of J receptor excitability produced by the raised PCP itself, suggest that movement of PDG out of the capillaries to the J receptors must be influenced primarily by forces governing diffusion, not filtration. 4. In addition to C of PDG there appear to be other factors that influence the responses of the receptors to PDG. PMID- 1522506 TI - Muscarinic responses of rat basolateral amygdaloid neurons recorded in vitro. AB - 1. Intracellular recordings were obtained from pyramidal-type neurons in the basolateral amygdaloid nucleus (BLA) in slices of rat ventral forebrain and used to compare the actions of exogenously applied cholinomimetics to the effects produced by electrical stimulation of amygdalopetal cholinergic afferents from basal forebrain. 2. Bath application of carbachol depolarized pyramidal cells with an associated increase in input resistance (Ri), reduced the slow after hyperpolarization (AHP) that followed a series of current-evoked action potentials and blocked spike frequency accommodation. All of these effects were reversed by the muscarinic antagonist atropine but not by the nicotinic antagonist hexamethonium. 3. Electrical stimulation of amygdaloid afferents within the external capsule evoked a series of synaptic potentials consisting of a non-cholinergic fast excitatory postsynaptic potential (EPSP), followed by early and late inhibitory postsynaptic potentials (IPSPs). Each of these synaptic potentials was reduced by carbachol in an atropine-sensitive manner. 4. Local application of carbachol to pyramidal cells produced a short-latency hyperpolarization followed by a prolonged depolarization. The hyperpolarization and depolarization to carbachol were blocked by atropine but not hexamethonium. 5. The carbachol-induced hyperpolarization was associated with a decrease in Ri and had a reversal potential nearly identical to that of the early IPSP. The inhibitory response was blocked by perfusion of medium containing tetrodotoxin (TTX), bicuculline or picrotoxin, while the subsequent depolarization was unaffected. On the basis of these data, it is concluded that the muscarinic hyperpolarization is mediated through the rapid excitation of presynaptic GABAergic interneurons in the slice. 6. The findings that the carbachol-induced depolarization was associated with an increase in Ri, often had a reversal potential below -80 mV, was sensitive to changes in extracellular potassium concentration and was blocked by intracellular ionophoresis of the potassium channel blocker caesium suggest that it resulted from a muscarinic blockade of one or more potassium conductances. 7. Repetitive stimulation of sites within the slice containing cholinergic afferents evoked a series of fast EPSPs followed by IPSPs. These non-cholinergic potentials were followed by a slow EPSP that lasted from 10 s-4 min. The slow EPSP was enhanced by eserine and blocked by atropine. It was also blocked by TTX or cadmium, indicating that it was dependent on spike propagation and calcium-dependent release of acetylcholine (ACh). 8. Stimulation of cholinergic afferents in the slice mimicked other effects produced by carbachol including blockade of the slow AHP and accommodation of action potential discharge and these actions were potentiated by eserine and blocked by atropine.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1522508 TI - Transmucosal electrical resistance in rabbit isolated gastric mucosa during exposure to acid. AB - 1. Transmucosal electrical resistance (Rt) and short-circuit current (Isc) were determined in rabbit isolated fundic mucosa. Under basal conditions, with a HCO(3 )-free HEPES-buffered solution (pH 7.4) bathing both sides of the mucosae, Rt was 161.5 + 5.0 omega cm2 and Isc 41.8 +/- 1.8 microA cm-2, and these values were not significantly different to values observed in HCO(3-)-buffered Krebs-Hensleit solution. 2. The basal Isc was inhibited by the Cl- channel blocker diphenylamine 2-carboxylate, and ouabain, but unaffected by the Na+ channel blocker amiloride (10(-5) M), consistent with electrogenic chloride secretion dependent upon a sodium gradient. Prostaglandin E2 (10(-7) M) stimulated an increase in Isc which was susceptible to inhibition by diphenylamine-2-carboxylate, but not amiloride, again consistent with Cl- secretion. 3. Stepwise acidification of the mucosal solution to pH 2.8 resulted in an increase in Rt of 43%, as compared with that measured with mucosal pH 7.4. Isc did not change during the acidification to pH 2.8, indicating retention of tissue viability. Increased Rt while Isc remained constant is consistent with an acid-induced decrease in the shunt (paracellular) conductance in this Cl(-)-secreting tissue. At pH less than 2.8, Rt declined rapidly and Isc declined and reversed, consistent with H+ back-diffusion. Scanning electron microscopic investigation of tissue exposed to mucosal pH 2.8 revealed little difference from control (pH 7.4) tissue, but there was considerable evidence of cellular damage and membrane disruption in tissue exposed to pH 1.8. 4. Acidification of the serosal solution did not increase Rt, which was maintained until pH 3.7, and then rapidly declined at pH less than 3.7. Bilateral acidification produced a mixed response; Rt increased, as for mucosal acidification, down to pH 2.8, after which there was a rapid decline in Rt following the pattern observed for serosal acidification. 5. Compared at a mucosal pH approximately 2.8, DIDS (4 x 10(-4) M) and amiloride (10(-3) M) inhibited the acid-induced increase in Rt, suggesting a role for both Cl(-)-HCO3- and Na(+)-H+ exchange in the response. In contrast, the acid-induced increase in Rt was unaffected by a lower concentration of amiloride (10(-5) M), acetazolamide and ouabain. Therefore, neither Na+ channels nor a Na+ gradient appear to be involved in the acid-induced increase in Rt.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1522509 TI - Effects of NG-nitro-L-arginine and L-arginine on regional cerebral blood flow in the cat. AB - 1. We studied the effects of NG-nitro-L-arginine (NOLA), a potent inhibitor of the L-arginine-nitric oxide pathway, and L-arginine, the precursor of nitric oxide, on regional cerebral blood flow, electrocortical activity and ex vivo cerebrovascular reactivity in the cat. Flow was measured via radiolabelled microspheres, and vascular responses were studied by measuring isometric tension of isolated middle cerebral arterial rings. 2. NOLA (30 mg kg-1 bolus followed by 1 mg kg-1 min-1 infusion) caused an approximately 40 mmHg elevation in the mean arterial blood pressure, a regionally heterogenous increase of the regional cerebrovascular resistance and a decrease in the regional cerebral blood flow 15 and 40 min after the start of its administration. In contrast L-arginine (30 mg kg-1 bolus followed by 10 mg kg-1 min-1 infusion) did not alter blood pressure, cerebrovascular resistance nor regional cerebral blood flow 15 min after the start of its administration. The NOLA-induced changes in tissue flow were the most pronounced in the cerebellum, pituitary and medulla oblongata, whereas there was no decrease in the flow of the cortex and white matter. 3. NOLA caused characteristic changes in total fronto-occipital EEG power and in power spectra which were unlikely to have been due to cerebral ischaemia. In addition, the ex vivo reactivity of the middle cerebral arteries showed signs of impaired endothelial nitric oxide synthesis: there were enhanced noradrenaline-induced contractions and N-ethoxycarbonyl-3-morpholino-sydnonimine (SIN-1)-induced relaxations and markedly attenuated acetylcholine- and ATP-induced relaxations after NOLA treatment. 4. The present data indicate that resting cerebral blood flow and cerebrovascular resistance are regulated by nitric oxide derived from L arginine in a regionally heterogenous way and that exogenous L-arginine availability is not a limiting factor in this nitric oxide generation. Possibly, both the vascular endothelium and the neurons contribute to this basal nitric oxide release. PMID- 1522510 TI - Effects of proteins on the permeability of monolayers of cultured bovine arterial endothelium. AB - 1. Monolayers of arterial endothelium on porous membranes were exposed to a pressure of 15 cmH2O at 37 degrees C, or of 30 cmH2O at 0 degree C. At constant pressure, the rate of liquid flow per unit area (Jv/A) through each monolayer decreased with time, in the way previously described for cultured endothelium. This phenomenon has been called sealing. After Jv/A stabilized, the pressure was reduced and the hydraulic permeability (Lp) of the endothelium was calculated from the relationship between Jv/A and pressure. Endothelium was seen to be damaged after some experiments at 37 degrees C, but appeared undamaged after experiments at 0 degree C. 2. Bovine serum albumin (BSA) did not influence the Lp of cultured endothelium. At 37 degrees C, the mean (+/- S.E.M.) endothelial Lp was 47.2 +/- 7.3 x 10(-7) cm s-1 cmH2O-1 (n = 10) in the presence of BSA (5 g (100 ml)-1). This is not significantly different from the mean (+/- S.E.M.) Lp of 53.4 +/- 9.0 x 10(-7) cm s-1 cmH2O-1 (n = 9) in the absence of added protein (P greater than 0.10). At 0 degree C also, there was no significant difference between mean Lps in the presence of BSA (0.1 g (100 ml)-1) and in the absence of added protein. 3. Solutions of BSA (5 g (100 ml)-1 or of the neutral polymer Ficoll 70 (4 g (100 ml)-1) did not exert any effective osmotic pressure across endothelium at 37 or 0 degrees C, respectively. 4. BSA (0.1 g (100 ml)-1) did not enable solutions of Ficoll 70 (4 g (100 ml)-1) to exert an effective osmotic pressure across endothelium at 0 degree C. 5. The mean Lp of endothelium at 0 degree C was significantly lower in the presence of cationized ferritin (CF; 0.1 g (100 ml)-1) than in the absence of added protein (P less than 0.001). Native ferritin (NF; 0.1 g (100 ml)-1) had no effect on Lp. 6. In the presence of CF (0.1 g (100 ml)-1), solutions of Ficoll 70 (4 g (100 ml)-1) exerted a mean effective osmotic pressure of 27.7 cmH2O (n = 5) across endothelium at 0 degree C. The mean effective osmotic pressure exerted across endothelium by solutions of Ficoll 70 (4 g (100 ml)-1) plus NF (0.1 g (100 ml)-1) was 1.2 cmH2O (n = 4). PMID- 1522511 TI - The pH dependence of chloride net flux in skeletal muscle fibres of Rana temporaria. AB - 1. The pH- and voltage-dependent Cl- conductance in frog muscle may be related to the chloride equilibrium potential, VCl,eq, rather than to the absolute membrane potential, Vm. This hypothesis was tested in thin depolarized frog muscle fibre bundles by investigating the influence of pH on 36Cl- efflux during Cl- net efflux upon removal of external Cl-, which offers a state far from Cl- equilibrium by changing VCl,eq instead of Vm. 2. Upon the change from Cl- equilibrium at 20 mM-Clo- to Cl- net efflux at zero [Cl-]o, Vm changed only approximately 10 mV, but the 36Cl- efflux rate increased about three times at pH 5.5 and decreased to less than one tenth of the equilibrium efflux rate at pH 9.8. The switch between 'acid' and 'alkaline' responses occurs at a pH between 6.4 ('acid response') and 7.2 ('alkaline response'). 3. Changing pH between 5.5 and 9.8 during Cl- net efflux showed an increase of 36Cl- net flux rate upon acidification and a decrease upon alkalinization. The reactions are opposite to those seen by pH shifts at chloride equilibrium. 4. The changes of net flux rate coefficients upon changes of pH were transient, especially the activation at low pH that relaxed significantly during about 10 min. 5. The results are consistent with the notion that the state of the gCl mechanism in frog muscle is related to (Vm-VCl,eq) rather than to the absolute potential alone. PMID- 1522512 TI - Respiratory modulation of the activity in sympathetic neurones supplying muscle, skin and pelvic organs in the cat. AB - 1. The respiratory-related modulation of activity in neurones of the lumbar sympathetic outflow to skeletal muscle, skin and pelvic organs was investigated in anaesthetized, paralysed and artificially ventilated cats, using single- and multi-unit recordings. The activity of the neurones was analysed with respect to the phrenic nerve discharge under various experimental conditions. 2. Neurones tentatively classified as muscle vasoconstrictor and visceral vasoconstrictor neurones exhibited two activity peaks, one caused by baroreceptor unloading during the declining phase of the second order blood pressure waves and a respiratory drive-dependent peak in parallel with inspiration. The two peaks were separated by depressions of activity in early inspiration and post-inspiration. After cutting vagus and buffer nerves the activity peak during inspiration remained and was followed and sometimes preceded by a depression of activity. 3. The majority of the neurones tentatively classified as cutaneous vasoconstrictor neurones exhibited no respiratory modulation in their activity. Others exhibited an activity peak in expiration, an activity peak in inspiration, or a respiratory profile similar to that in muscle vasoconstrictor neurones. During increased respiratory drive (induced by hypercapnia) some neurones with unmodulated activity changed to an inspiratory or an expiratory pattern. Neurones discharging predominantly in inspiration projected preferentially to hairless skin. 4. Neurones which were tentatively classified as sudomotor neurones discharged predominantly in early expiration. 5. Some preganglionic neurones which were tentatively classified as motility-regulating neurones discharged during expiration. The majority of these neurones disclosed no respiratory modulation of their activity. 6. The study shows that different types of neurone of the lumbar sympathetic system exhibit distinct patterns of respiratory modulation in their activity. We conclude that the type and degree of central coupling between respiratory system and sympathetic nervous system may vary according to the destination of the sympathetic neurones. PMID- 1522513 TI - Longitudinal chromatic aberration and emmetropization: results from the chicken eye. AB - 1. Due to the chromatic dispersion of the ocular media, the focal length of the optics of the eye is about 3 diopters longer for red light than for blue light. Because emmetropization in the chicken (Gallus domesticus) does not require colour cues and operates properly in monochromatic light, one can, therefore, expect that chickens raised in red light become more myopic (with longer eyes) than chicks raised in short wavelength light. Prior to conducting this experiment, we matched the brightness of both light conditions by means of flicker electroretinograms such that equiluminance was obtained for the chickens. 2. Unexpectedly, refractive development was not different from controls in white light for either red or near-ultraviolet light. 3. We tested whether the visual mechanisms guiding refractive development were still sensitive to defocus under both illuminations by treating the chicks with spectacle lenses. 4. Similar to a previous experiment in white light, the growth of the eye in red light also changed such that it compensated for the imposed defocus. It failed to do so, however, in near-ultraviolet light. 5. A histological analysis of the sampling intervals for the ultraviolet receptor system revealed that its spatial resolving power was too low to detect the defocus imposed by the lenses, whereas the long wavelength receptors provided sufficiently good visual acuity. 6. The results show that, during emmetropization, the chicken eye elegantly bypasses the problem of multiple chromatic focal planes by having a low sensitivity to defocus in the blue end of the spectrum. Because the chromatic dispersion function is steep in the blue range but flat at the red end of the spectrum, the remaining chromatic defocus in the spectral range of high visual acuity is low and may match the depth of field of the eye. PMID- 1522514 TI - Cholinergic activation of a non-selective cation current in canine gastric smooth muscle is associated with contraction. AB - 1. The effects of acetylcholine on membrane electrical properties of single smooth muscle cells dissociated from the circular layer of the canine gastric corpus were investigated using the nystatin perforated patch technique. Cells retained their ability to contract during recording, making it possible to correlate changes in membrane potential and membrane currents with contractions. 2. Acetylcholine caused depolarization from -59 +/- 8 mV to -18 +/- 7 mV (means +/- S.D., n = 12) with no generation of action potentials. The depolarization was associated with a membrane conductance increase, consistent with acetylcholine activating an inward current. In addition, acetylcholine caused contraction of cells to 58% of initial length. Both depolarization and contraction were reversible and were antagonized by atropine. 3. Under voltage clamp, acetylcholine activated inward current associated with increased current noise. The current-voltage relationship of the acetylcholine-induced current was studied at steady-state voltages and with voltage ramp commands. The inward current was largest between -40 and -20 mV and reversed direction to outward close to 0 mV (reversal potential, Erev = +3 +/- 9 mV). Reduction of external Na+ concentration to 21 mM shifted Erev to -42 +/- 5 mV, as predicted for a non-selective cation current. The conductance activated by acetylcholine (gACh) increased sigmoidally with depolarization, with about 2.5 nS activated at 0 mV. 4. Cells consistently contracted upon stimulation with acetylcholine, even when studied under voltage clamp at potentials as negative as -100 mV. This was consistent with muscarinic receptor activation causing release of Ca2+ from internal stores. When cells were bathed in Ca(2+)-free solutions, the first application of acetylcholine elicited normal inward current and contraction. Thereafter, both inward current and contractions were greatly diminished or absent, suggesting that the stores of Ca2+ had been depleted. 5. Caffeine caused reversible contraction and activation of inward current similar to that elicited by acetylcholine. 6. It is concluded that muscarinic stimulation of canine gastric smooth muscle cells involves activation of a non-selective cation conductance and is consistently accompanied by contraction. The release of Ca2+ from internal stores may be a common trigger for both events. PMID- 1522515 TI - Effect of temperature on relaxation rate and Ca2+, Mg2+ dissociation rates from parvalbumin of frog muscle fibres. AB - 1. Influence of temperature on relaxation rate as a function of isometric tetanus duration and on Ca2+ and Mg2+ dissociation rates from purified parvalbumin (PA) was examined to test the hypothesis that PA promotes relaxation in frog skeletal muscle. Single fibres and PA IVB from Rana temporaria skeletal muscle were utilized. 2. The magnitude of slowing of relaxation rate with increasing tetanus duration, relative to the final, steady value of relaxation rate, is 3-fold greater at O than at 10 degrees C. 3. In the 0-10 degrees C range, the Q10 for relaxation rate increases from 2.3 to 3.7 with increasing tetanus duration. 4. Dissociation of Ca2+ and Mg2+ from PA exhibited: (i) rate constants of 1.03 +/- 0.03 s-1 (mean +/- S.D., n = 5) and 3.42 +/- 0.14 s-1 (n = 5) at 20 degrees C and (ii) Q10 values of 2.3 and 1.9 in the 0-20 degrees C range, respectively. 5. Time courses of slowing of relaxation rate with increasing tetanus duration and recovery of relaxation rate with rest after a prolonged tetanus at 10 degrees C are similar to rates of dissociation of Mg2+ and Ca2+ from PA, respectively, as previously reported at 0 degree C. 6. Both the temperature dependence of the relative magnitude of slowing of relaxation rate and the increased Q10 of relaxation rate with increased tetanus duration can be explained if the Q10 for Ca2+ uptake by the sarcoplasmic reticulum is greater than the Q10 for Ca2+ sequestration by PA during relaxation. When Ca2+ and Mg2+ dissociation rates from PA at various temperatures are compared to other proposed indicators of PA function, it is concluded that PA facilitates relaxation of frog skeletal muscle in the 0-20 degrees C range. PMID- 1522516 TI - Evidence that a long latency stretch reflex in humans is transcortical. AB - 1. The hypothesis that the long latency reflex response to muscle stretch in humans uses a transcortical pathway was tested by looking for convergence onto cortical neurones in eleven normal subjects. 2. Postsynaptic events in single flexor pollicis longus (FPL) motoneurones were derived from changes in the firing probability of individual FPL motor units. 3. Extension of the terminal phalynx of the thumb resulted in both short latency and long latency facilitations of individual FPL motoneurones. These were not reproduced by electrical stimulation of afferents in the terminal phalynx. Magnetic stimulation over the contralateral motor cortex produced strong, short latency facilitation of FPL motoneurones. 4. When the facilitation produced by stimulation over the cortex was superimposed on the long latency facilitation produced by extension of the thumb, the facilitation produced by both stimuli was greater than the sum of the individual facilitations produced by either stimulus given alone. This was not the case when the superimposition occurred on the short latency response to stretch. 5. We conclude that afferent systems excited by the stretch of FPL converge onto cortical neurones which are known to facilitate motoneurones. Thus the cortex is likely to contribute to the long latency stretch reflex in humans. PMID- 1522517 TI - Relationship between parasternal and external intercostal muscle length and load compensatory responses in dogs. AB - 1. The effects of tracheal occlusion on peak parasternal (PA) and external intercostal (EI) (3rd interspace) EMG activities were examined at different end expiratory lung volumes both above and below functional reserve capacity (FCR) in anaesthetized, vagotomized and spontaneously breathing dogs. 2. Parasternal (PA) and external intercostal (EI) muscle lengths were monitored in situ. The difference in peak EMG activity between free and occluded breaths (test breaths) was related to the coincident peak change in intercostal muscle length (delta L) for each muscle, respectively. 3. At FRC, tracheal occlusion resulted in compensatory augmentation of peak EI, but little change in peak PA EMG activities. At lung volumes below FRC, airway occlusion resulted in augmentation of both PA and EI activities. Responses to airway occlusion at lung volumes above FRC were variable. The magnitude and duration of these changes in EMG, however, could be linearly related to the value of delta L. With delta L = 0, there was no change in peak EI or PA EMG; for values of delta L less than 0, there was attenuation of EI and PA EMG; for delta L greater than 0, there was enhancement of EI and PA EMG activation. 4. The magnitude of the changes in EMG activity in response to tracheal occlusion was more prominent for the EI muscle compared to the PA, the latter of which are known to have much fewer muscle spindles than EI muscle. 5. Our results suggest that a difference in end-inspiratory muscle length between the control and occluded breaths is a stimulus for the intercostal response to applied loads implicating muscle spindles as the predominant receptor moderating these responses. We hypothesize that when delta L = 0, no change in EMG occurs since the spindles sense no change in muscle length. When delta L less than 0 (i.e. peak muscle length during the occluded breath is shorter than control) muscle spindles would be disengaged, resulting in a disfacilitation of EMG activity. Where delta L greater than 0 (i.e. peak muscle length during the occluded breath is longer than control), muscle spindles are stimulated, resulting in enhancement of EMG activity. 6. Additional doses of Nembutal (20 mg), which produced significant changes in breathing pattern, did not affect the magnitude of the load compensatory responses. PMID- 1522518 TI - Response characteristics of the cells of cortical area 21a of the cat with special reference to orientation specificity. AB - 1. Extracellular recording using tungsten-in-glass microelectrodes was conducted on 115 neurons in area 21a of fifteen anaesthetized cats. Quantitative analysis using computer-controlled display and collecting routines were used to investigate the excitatory and inhibitory regions of the receptive field and to see if interaction, within and between these regions, contributed to the response properties of the cells. 2. The responses of the cells in the sample appeared to arise from a single, homogeneous class. All cells had single discharge regions which responded with composite ON/OFF firing to a stationary flashing bar. The same region also responded to moving light and dark bars and edges. There was little evidence of inhibition as measured by the suppression of spontaneous or induced firing. Most cells had relatively small receptive fields (primary width: mean = 2.1 +/- 0.9 deg (S.D.); n = 108), all were binocular and were located within 15.0 deg of the visual axes. 3. All cells responded well to slowly moving stimuli but generally failed to respond to stimuli moving faster than 10.0 deg s 1. All responses were bi-directional and, although many showed evidence of length summation, there was no sign of linear summation. 4. Despite the absence of significant sideband inhibition many cells were acutely tuned for orientation (half-width at half-height: mean = 15.6 +/- 5.3 deg; n = 48). To investigate this property further, cells were analysed to assess the effect of changing the length of a moving bar stimulus on the acuteness of the orientation tuning curve. Short bars, of similar length to the width of the receptive field, had orientation tuning curves of equivalent sharpness to those obtained with longer bars. 5. The equivalence of orientation tuning for long and short bars stands in contrast to the results obtained for both simple (S) and complex (C) cells of the striate cortex where tuning for the longer bar is sharper than that for the shorter. The result from area 21a cells is consistent with the absence of sideband inhibition and can be related to an input from the striate cortex that passes through a threshold barrier. 6. The orientation tuning of cells of area 21a can be explained if it is assumed that they receive their major input from C or complex cells of the striate cortex in which firing must reach a threshold frequency to activate the recipient cell. PMID- 1522519 TI - Neural regulation of acetylcholine receptors in rat neonatal muscle. AB - 1. The neuronal regulation of the developmental decline in skeletal muscle acetylcholine (ACh) receptors was studied by comparing the effects of sciatic nerve section or of neuromuscular blockade with botulinum toxin (BoTX) on this decline in neonatal and adult rats, using 125I-alpha-bungarotoxin (125I-BTX) as a ligand for the receptor alpha-subunit. 2. The decline in 125I-BTX binding site concentration in neonatal rat triceps surae muscle homogenates towards low, adult levels followed a simple exponential with a time constant of 8 days. This decline occurred while the muscle is still rapidly growing, before the postnatal increase in numbers of sodium channels. It also preceded the decline in muscle ACh receptor alpha-subunit mRNA, reported in other studies, suggesting that subunit levels are not regulated only by mRNA availability. 3. Muscle denervation in the first two weeks of life prevented this developmental decline. Denervation increased the concentration of 125I-BTX binding sites but the magnitude of this increase became progressively smaller as the muscle matured, showing that removal of innervation during adult life does not revert the muscle, in toto, to its pre innervation state. 4. Blockade of neuromuscular activity with BoTX increased 125I BTX binding sites to a lesser extent than muscle denervation during neonatal life. This lesser effect of BoTX blockade contrasts with the equal effects of BoTX blockade and denervation in the adult. PMID- 1522520 TI - Changes of intracellular pH due to repetitive stimulation of single fibres from mouse skeletal muscle. AB - 1. The performance of skeletal muscle during repetitive stimulation may be limited by the development of an intracellular acidosis due to lactic acid accumulation. To study this, we have measured the intracellular pH (pHi) with the fluorescent indicator BCECF (2',7'-bis(carboxyethyl)-5(6)- carboxyfluorescein) during fatigue produced by repeated, short tetani in intact, single fibres isolated from the mouse flexor brevis muscle. 2. The pHi at rest was 7.33 +/- 0.02 (mean +/- S.E.M., n = 29, 22 degrees C). During fatiguing stimulation pHi initially went alkaline by about 0.03 units (maximum alkalinization after about ten tetani). Thereafter pHi declined slowly and at the end of fatiguing stimulation (tetanic tension reduced to 30% of the original; 0.3Po), pHi was only 0.063 +/- 0.011 units (n = 14) more acid than in control. 3. We considered three possible causes of acidosis being so small in fatigue: (i) a high oxidative capacity so that fatigue occurs without marked production of lactic acid; (ii) an effective transport of H+ or H+ equivalents out of the fibres; a high intracellular buffer power. 4. The oxidative metabolism was inhibited by 2 mM cyanide in three fibres. After being exposed to cyanide for 5 min without stimulation, the tetanic tension was reduced to about 0.9 Po and pHi was alkaline by about 0.1 units. The fibres fatigued faster in cyanide and the pHi decline in fatigue was more than twice as large as that under control conditions. 5. Inhibition of Na(+)-H+ exchange with amiloride resulted in a slow acidification of rested fibres; resting pHi was not affected by either inhibition of HCO3(-)-Cl exchange with DIDS (4,4'-diisothiocyanatostilbene-2,2'-disulphonic acid) or inhibition of the lactate transporter with cinnamate. 6. Fibres fatigued in cinnamate displayed a markedly larger acidification (approximately 0.4 pH units) and tension fell more rapidly than under control conditions; inhibition of Na(+) H+ and HCO3(-)-Cl- exchange did not have any significant effect on fatigue. 7. The intracellular buffer power, assessed by exposing fibres to the weak base trimethylamine, was about 15 mM (pH unit)-1 in a HEPES-buffered solution (non-CO2 or intrinsic buffer power) and about 33 mM (pH unit)-1 in a bicarbonate-buffered solution. Somewhat higher values of the intrinsic buffer power was obtained from changes of the partial pressure of CO2 (PCO2) of the bath solution. Application of lactate or butyrate frequently gave an infinite buffer power, which indicates that powerful pH-regulating mechanisms operate in these cases.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1522521 TI - Opioidergic inhibition of flexor and extensor reflexes in the rabbit. AB - 1. Recordings were made from gastrocnemius medialis (GM), semitendinosus (ST) and tibialis anterior/extensor digitorum longus (TA/EDL) motor nerves during mechanical and electrical stimulation of the skin of the foot in decerebrated and spinalized rabbits. 2. GM motoneurones were excited from the heel and not from the toes, whereas TA/EDL responded to stimulation at the toes but not at the heel. ST also responded to electrical and mechanical stimulation at the toes, but there was a disparity between the effects of the two types of stimuli when they were applied at the heel: ST motoneurones fired in response to electrical stimulation of the heel but showed only an 'off' response to mechanical stimulation at this site. 3. The opioid antagonist naloxone caused a dose dependent increase in all reflexes evoked by electrical stimulation of the skin. The heel-GM, toes-ST and toes-TA/EDL reflexes all increased to more than 3 times control levels with naloxone, which also caused significant decreases in the latencies of these reflex responses. On the other hand, the heel-ST response increased to just 1.4 times control levels and showed no decrease in latency with the opioid antagonist. 4. These data suggest that segmental withdrawal reflex pathways in the rabbit are suppressed by endogenous opioid peptides. This opioid mediated inhibition seems to operate non-selectively on reflex pathways between cutaneous afferents and motoneurones. PMID- 1522522 TI - The perceptions of force and of movement in a man without large myelinated sensory afferents below the neck. AB - 1. Motor memory and the sense of effort have been investigated in a man with a complete large fibre sensory neuropathy for over 16 years. The perceptions of pain, heat, cold and muscular fatigue remained but he was without perceptions of light touch and proprioception below the neck. 2. The subject was able to discriminate weights held in the hand with an accuracy only slightly worse than control subjects (20 g in 200 g) when forearm movement and visual inspection were allowed. With eyes shut however he could only distinguish a weight of 200 g from 400 g. It is concluded that a crude sense of effort remains which may have a peripheral origin. 3. A limited motor memory was also present, which allowed him to maintain a posture or continue a simple repetitive movement. No novel movement was possible without visual feedback. 4. Differences in movement ability between this subject and others with similar if less pure sensory neuropathies are ascribed to rehabilitation. PMID- 1522523 TI - The relationship between contraction and intracellular sodium in rat and guinea pig ventricular myocytes. AB - 1. The contraction, measured optically, and the intracellular Na+ activity (aNai), measured with the Na(+)-sensitive fluorescent dye SBFI, have been recorded simultaneously in rat and guinea-pig ventricular myocytes. 2. In rat and guinea-pig ventricular myocytes at rest, aNai was 7.8 +/- 0.3 mM (n = 4) and 5.1 +/- 0.3 mM (n = 16), respectively. 3. When both rat and guinea-pig ventricular myocytes were stimulated at 1 Hz after a rest there was usually a gradual increase in twitch shortening (referred to as a 'staircase') over several minutes accompanied by an increase in aNai over a similar time course. Twitch shortening increased by 21 +/- 3% (n = 6) and 20 +/- 4% (n = 16) (of steady-state twitch shortening during 1 Hz stimulation) per millimolar rise in aNai in rat and guinea pig ventricular myocytes, respectively. 4. When rat and guinea-pig ventricular myocytes were exposed to strophanthidin to block the Na(+)-K+ pump, there were increases in twitch shortening and aNai over similar time courses. Twitch shortening increased by 24 +/- 4% (n = 5) and 20 +/- 3% (n = 10) (of control twitch shortening) per millimolar rise in aNai in rat and guinea-pig ventricular myocytes respectively. 5. The inotropic effect of cardiac glycosides, such as strophanthidin, is widely regarded to be principally the result of the rise in aNai. The similarity of the relation between twitch shortening and aNai during the staircase and on application of strophanthidin suggests that the progressive increase in the strength of contraction during the staircase was also linked to the rise in aNai. 6. In guinea-pig, but not rat, ventricular myocytes there was hysteresis in the relation between twitch shortening and aNai on application and wash-off of strophanthidin. This indicates that strophanthidin has another inotropic action in guinea-pig ventricular myocytes. 7. A computer model of excitation-contraction coupling has been developed to simulate the staircase and the action of cardiac glycoside and to account for the relation between contraction and intracellular Na+. PMID- 1522524 TI - Developmental changes in troponin T isoform expression and tension production in chicken single skeletal muscle fibres. AB - 1. The Ca2+ sensitivity of tension development was characterized in single skinned fibres from the slow anterior latissimus dorsi (ALD), fast posterior latissimus dorsi (PLD), and fast pectoralis major (PM) muscles of the chicken at adult and neonatal (2 weeks post-hatch) stages of development. In the adult, the PM was most sensitive, the ALD intermediate, and the PLD least sensitive to Ca2+. 2. PM and PLD fibres were less sensitive to Ca2+ at the neonatal stage of development than in the adult. However, ALD fibres exhibited no age-dependent changes in Ca2+ sensitivity. 3. Characterization of regulatory protein composition indicated that the PM and PLD fibres had identical fast isoforms of troponin C and troponin I at each developmental stage examined, but there were muscle-specific and age-dependent expressions of troponin T isoforms in these fibres. 4. In the ALD fibres, identical slow isoforms of troponin C, troponin I and tropomyosin were found at each stage. In addition, the troponin T isoform that was present did not change with age. 5. The results suggest a relationship between the specific troponin T isoform composition of individual muscle fibres and their calcium sensitivities of tension development. PMID- 1522525 TI - Changes in synovial PO2 and blood flow in the rabbit knee joint due to stimulation of the posterior articular nerve. AB - 1. Experiments were performed to measure the partial pressure of oxygen in the synovial fluid (Ps,O2) of the normal rabbit knee joint and assess the extent to which this varied with changes in knee joint blood flow. 2. With the hypodermic needle oxygen electrode sited just within the synovial cavity, Ps,O2 values ranged from 25 to 72 mmHg with a mean of 48.2 +/- 3.1 (S.E.M.; n = 18). 3. Ps,O2 was found to decrease with increasing depth of penetration of the oxygen electrode. Lowest values were observed close to the articular cartilage. 4. Electrical stimulation of the posterior articular nerve (PAN) of the knee resulted in vasoconstriction of knee joint blood vessels which was accompanied by a decrease in Ps,O2. The frequency-response and voltage-response profiles to electrical stimulation of PAN, although differing in magnitude, showed a high degree of correlation between blood flow and Ps,O2. 5. As judged by the conduction velocity, the vasoconstrictor response to nerve stimulation was mediated by unmyelinated nerve fibres, presumed to be sympathetic postganglionic fibres. 6. In view of the low Ps,O2 values occurring deep within the joint, avascular structures such as cartilage could be subject to injury if sustained reduction in synovial blood flow occurred. This could be a contributory factor in the pathogenesis of degenerative and inflammatory joint diseases. PMID- 1522526 TI - Changes in presynaptic inhibition of afferents to propriospinal-like neurones in man during voluntary contractions. AB - 1. The possibility was investigated that the facilitation of the transmission in the propriospinal-like system during voluntary contraction, documented in the companion paper (Burke, Gracies, Mazevet, Meunier & Pierrot-Deseilligny, 1992), is due to a decrease in presynaptic inhibition of afferents projecting to propriospinal-like neurones. 2. The radial nerve was stimulated to evoke presynaptic inhibition of the monosynaptic Ia projections to forearm flexor motoneurones (Berardelli, Day, Marsden & Rothwell, 1987) and, hopefully, of the afferent input to propriospinal-like neurones projecting to these motoneurones. 3. The propriospinal-like excitation of forearm motoneurones evoked from mixed afferent inputs was depressed by radial nerve stimulation, and this depression was long-lasting (200 ms). Despite the convergence of mixed nerve and cutaneous afferents onto common propriospinal-like neurones, the radial stimulation did not depress the cutaneous-induced excitation. This differential effect and the time course of the depression suggest that it results from presynaptic inhibition of mixed nerve afferents (presumably large muscle afferents) projecting to propriospinal-like neurones. 4. With voluntary contractions, phasic or tonic, the radial-induced depression of the propriospinal-like excitation evoked by mixed nerve afferents was much greater than at rest, but the cutaneous-evoked excitation was unchanged. Thus, with voluntary contractions, there was no evidence of decreased gating of the afferent input to propriospinal-like neurones whether the input was of muscle or cutaneous origin and it is concluded that changes in presynaptic inhibition cannot account for the facilitation of the transmission in the propriospinal-like system during voluntary contraction. 5. By contrast, presynaptic inhibition of the monosynaptic Ia projections to motoneurones was consistently reduced at the onset of contraction, and to a much lesser extent during a weak tonic contraction. PMID- 1522527 TI - The role of nociceptors of cutaneous veins in the mediation of cold pain in man. AB - 1. To test the hypothesis that nociceptors of cutaneous veins mediate cold pain, we studied in man the time course of pain intensity and skin sensibility in relation to both intracutaneous and vein wall temperature during cooling of the dorsum of the hand by ice water before and after perivenous and intravenous nerve block. 2. Upon exposure to cold, intracutaneous temperatures fell exponentially (half-life/45-75s) within 10 min to a median of 4 degrees C (range 2-9 degrees C) and returned to baseline with a similar time course during rewarming (half life/40-85 s). 3. Skin sensitivity to pin prick disappeared and returned at almost the same intracutaneous temperatures (16-26 degrees C). Pain, however, occurred and eve increased when the skin was already numb. 4. Pain occurred during cooling and disappeared during rewarming at vein wall temperatures between 23 and 28 degrees C and its intensity increased to a maximum of 72-100% of visual analogue scale as vein wall temperature decreased to a minimum of 9 degrees C (range 7-10.5 degrees C). 5. the pain intensity-vein wall temperature relations derived from skin cooling with threshold temperature changes between -5.5 and -9 degrees C and slopes between 2.2 and 3.3 were congruent to those derived from intravenous cooling in a previous study to ours. 6. Perivenous and intravenous nerve block, which did not alter the sensitivity of skin and periosteum, relieved cold pain markedly (perivenous block) or completely (intravenous block). 7. These observations are consistent with the hypothesis that nociceptors of cutaneous veins mediate cold pain in humans. PMID- 1522528 TI - The effect of the stimulation pattern on the fatigue of single motor units in adult cats. AB - 1. The main purpose of this study was to examine the effects of two subtly different stimulus patterns on the force developed by fast-twitch, fatiguable motor units in a cat hindlimb muscle during control (pre-fatigue) and fatiguing contractions. 2. The peak force and the force-time integral responses of nineteen high fatigue (FF) and three intermediate fatigue (FI) motor units of the tibialis posterior muscle in five deeply anaesthetized adult cats were measured at selected times during the course of a 360-s fatigue test. 3. The fatigue test involved a pseudo-random alternation of two patterns of stimulation. One pattern (regular) was composed of a train of stimuli with constant interpulse intervals, set at 1.8 x the twitch contraction time of each unit (interval range, 27-51 ms), and delivered for 500 (or 400) ms. For the total (FF + FI) motor-unit sample, the mean (+/- S.D.) stimulation frequency was 26 +/- 4 Hz (range, 19-37 Hz). The other stimulus pattern (optimized) consisted of three initial stimuli with short (10 ms) interpulse intervals, followed by a constant interpulse-interval train that was adjusted (interval range, 29-62 ms; frequency, 23 +/- 5 Hz; frequency range, 16-36 Hz) such that the total train had the same number of pulses, and the same average frequency and duration as the regular train. 4. The stimulus trains were delivered at 1 s-1 for 360 s, using three-train sequences of each pattern, randomly alternating with one another. The response of the third train in each sequence was selected for the force measurements. The force profile obtained from the fatigue test was subsequently decomposed into two profiles: one attributable to regular and one to optimized stimulation. 5. During the initial responses to the fatigue test, the optimized stimulus pattern produced significantly more force than the regular stimulus pattern. For FF units, the mean increase in peak force (141%) was significantly greater than the increase in the force-time integral (59%). 6. All motor units exhibited an initial potentiation of peak force with the regular stimulation pattern, whereas peak force declined monotonically with the optimized pattern. In contrast, the force-time integral potentiated in the first 30 s for both regular and optimized stimulus patterns. 7. Each motor unit maintained an increased force response to optimized stimulation during the fatigue test, with the greatest relative increase occurring about 120 s into the test, well after the potentiation effect had subsided.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1522529 TI - Orofacial manifestations of the systemic mycoses. AB - Aspergillosis, cryptococcosis and zygomycosis (mucormycosis) are overall the most common systemic mycoses but histoplasmosis is particularly endemic in parts of central USA and other areas worldwide. Orofacial lesions caused by systemic mycoses have rarely been reported in the past though they have been recorded particularly in outdoor workers from geographic areas with a high prevalence of infection and occasionally in immunocompromised individuals. Increasing world wide travel, and the dramatic increase in numbers of immunocompromised persons, especially those with human immunodeficiency virus (HIV) disease, have been responsible for an increase in reports and other studies of orofacial disease in systemic mycoses and new opportunists are now being recognized. Those in Oral Medicine and Pathology must now be aware of the possibility of a systemic mycosis as the cause of chronic oral ulceration, chronic maxillary sinus infection, or bizarre mouth lesions, especially in patients with HIV disease, lymphoproliferative disorders, or diabetes mellitus, or in those who have been in endemic areas. Diagnosis and management should be undertaken in consultation with a physician with appropriate expertise, as pulmonary and other systemic infection may well be present. This paper reviews the eight main systemic mycoses. PMID- 1522530 TI - The role of saliva in aggregation and adherence of Pseudomonas aeruginosa in patients with cystic fibrosis. AB - The aggregation and adherence activity of P. aeruginosa, mediated by whole saliva from cystic fibrosis (CF) patients and non-CF subjects, was investigated. CF saliva-mediated aggregation of P. aeruginosa was stronger than the activity of non-CF saliva. Likewise, P. aeruginosa adherence to buccal epithelial cells (BEC) of CF patients was stronger than to BEC of non-CF subjects. Adherence of non mucoid P. aeruginosa to BEC of CF patients was increased by saliva, whereas the mucoid variant was not. CF patients colonized with P. aeruginosa showed higher adherence of the non-mucoid variant than non-colonized CF patients. CF patients with high saliva-mediated adherence of non-mucoid P. aeruginosa also had high salivary aggregation activity. Increased CF saliva-mediated aggregation activity may be linked to the increased non-mucoid P. aeruginosa adherence to BEC of CF patients. PMID- 1522531 TI - Oral carriage of yeasts, coliforms and staphylococci in patients with advanced malignant disease. AB - Many patients with advanced cancer have oral problems, some of which may have a microbiologic basis. The oral flora in such patients has not, however, been characterized. This study has assessed the prevalence of yeasts, coliforms and coagulase positive staphylococci in the oral flora of 197 patients with advanced cancer. Both imprint cultures (n = 197) and oral rinses (n = 161) were collected. Yeasts were isolated from the mouths of 83% of the patients, coliforms from 49.1% and coagulase-positive staphylococci from 28%. All these percentages are considerably in excess of reported levels for healthy individuals. The results indicate a loss of colonization resistance of the oral mucosa in terminal cancer, with potential implications for the development of mouth care regimes for such patients. PMID- 1522532 TI - Gingival cyst in adults. AB - A retrospective study is reported of 14 cases of gingival cyst of adults. Clinical data were pooled with well-documented cases in the literature. Most cases occurred in the 5th and 6th decades and in the premolar-canine-incisor area. Microscopically, the epithelial lining ranged from a thin, flat to cuboidal layer, 1-3 cells thick, resembling reduced enamel epithelium, to a nonkeratinized stratified squamous epithelium without rete ridges, of about 5-6 layers. Epithelial cells were frequently atrophic and this could involve the full thickness of the epithelium leaving an amorphous band of eosinophilic material. Plaque-like epithelial thickenings are sometimes present. Multicystic or "botryoid" forms may occur. The cysts are of developmental origin, arising either from basal cell extensions of overlying epithelium; or from postfunctional odontogenic epithelial residues of the dental lamina or rests of Malassez; or from junctional epithelium in the gingival crevice. The latter theory of origin is favored. PMID- 1522533 TI - Epidermal growth factor receptor in odontogenic cysts and tumors. AB - The expression of epidermal growth factor receptor (EGFR) was investigated in 67 cases of odontogenic cysts and 35 cases of odontogenic tumors using monoclonal antibody to EGFR (Biomarker, Israel) to determine the presence and significance of this transmembrane growth factor receptor. The cystic epithelial cells of odontogenic cystic lesions (keratocyst 60%; primordial cyst 75%; radicular cyst 35%; and follicular cyst 47.4%) were positive to EGFR staining. Cytochemical characterization of EGFR in those cystic epithelium was cell membrane positive type as in the normal epithelium. No expression of EGFR was found in the odontogenic tumors. This diversity of EGFR represents no binding activity of EGF, or loss of EGFR in the tumor cell upon EGFR mediated growth in odontogenic tumors was suggested a different tumor cell growth factor status or microenvironment in cell proliferation mechanism at the cellular level in cysts and tumors of odontogenic origin. PMID- 1522534 TI - Primary malignant lymphoma of the salivary gland: a tumor of mucosa-associated lymphoid tissue. AB - The clinical, morphologic and immunohistochemical features of 10 cases of the low grade mucosa-associated lymphoid tissue (MALT) lymphoma of salivary glands are described. Although the initial histologic diagnosis in nine of these cases was myoepithelial sialadenitis, the diagnosis of primary salivary gland MALT lymphoma was based on the demonstration of light chain restriction and on morphologic characteristics. Histologic study showed a characteristic cytology, which included centrocytoid cells (composed of small centrocytes and monocytoid B cells) and a varying degree of plasma cell differentiation; the occurrence of epithelial or acinar invasion by neoplastic centrocytoid cells; and the presence of reactive lymph follicles among the neoplastic cells. Furthermore, multinucleate giant cells resembling Warthin-Finkeldey cells were detected in seven cases. In the light of these findings, cases previously diagnosed as myoepithelial sialadenitis require careful assessment and nine out of 32 cases are, in reality, examples of primary salivary gland MALT lymphomas. Immunohistochemical analysis of paraffin sections revealed the following characteristic immunophenotype of MALT lymphoma: L26, KiB3 and LN2 positive, and a monotypic immunoglobulin pattern (predominantly IgM/kappa). It was of interest that salivary gland parenchyma, infiltrated by neoplastic centrocytoid cells, reacted with LN3 for cells expressing human leukocyte antigen-DR (HLA-DR) antigens. Whereas salivary gland epithelia devoid of a neoplastic invasion were invariably negative for LN3. This suggests a lymphocyte-mediated role in salivary epithelial HLA-DR expression. It appears that HLA-DR expression is an inducible phenomenon in MALT lymphomas of salivary gland. PMID- 1522535 TI - Possible premalignant character of oral lichen planus. The Amsterdam experience. AB - In the present paper the 21-yr experience of the Department of Oral and Maxillofacial Surgery and Oral Pathology, and the Department of Otorhinolaryngology of the Free University Hospital, Amsterdam, is reported with regard to the possible premalignant character of oral lichen planus. The study consists of two parts: 1) the follow-up of 113 patients with histopathologically proven oral lichen planus, and 2) a search for lichen planus in 727 patients who have been admitted for oral cancer. Three patients with histopathologically proven lichen planus developed a squamous cell carcinoma in an average follow-up period of 7 yr. In the 727 patients with oral cancer, two additional patients with the simultaneous occurrence of oral lichen planus were observed. Our experience gives some but not very strong support to the hypothesis that oral lichen planus is a premalignant condition. PMID- 1522536 TI - A chemostat study on proline uptake and metabolism of Leishmania donovani. AB - Leishmania donovani grew in the chemostat on proline as its sole carbon and energy source at a maximum growth rate of 1.39 divisions per day. The efficiency of proline metabolism decreased with increasing external proline concentration. The internal concentration of proline and its intracellular metabolites was low when proline was the growth rate limiting substrate and high when proline was available in excess. In time-course experiments proline uptake leveled off after 30 min, independent of the culture conditions prior to the experiment. Proline uptake depended on the external proline concentration in a manner that is best described as the combination of an enzymatic and a diffusion component. Adaptation to different proline concentrations did not occur and no evidence was found that proline is actively transported by L. donovani. PMID- 1522537 TI - Isoenzyme comparison of axenic Giardia lamblia strains. AB - We obtained isoenzyme patterns by polyacrylamide gradient gel electrophoresis (PGGE) of water-soluble protein fractions prepared from trophozoites of 11 axenic G. lamblia strains. The strains were isolated from animals and humans (both symptomatic and asymptomatic) from various geographic locations. Isoenzymes were also separated by isoelectric focusing. Of 12 enzymes attempted, eight exhibited well-defined and reproducible isoenzyme patterns by PGGE, based on which the strains were grouped into four zymodemes. Although the 11 strains were grouped into four zymodemes based on PGGE, no correlation between zymodeme and the known characteristics of the strains existed. Thus, a high degree of characteristic sharing appears to occur among genetically different G. lamblia strains. PMID- 1522538 TI - Ciliate protozoa in the rumen of Kafue lechwe, Kobus leche kafuensis, in Zambia, with the description of four new species. AB - The composition of the rumen ciliate fauna in 76 Kafue lechwe inhabiting a limited area in Zambia was surveyed and five genera containing 24 species with 16 formae belonging to the family Ophryoscolecidae were identified. Four new species belonging to Diplodiniinae were recognized and described as Diplodinium lochinvarense n. sp., Diplodinium leche n. sp., Diplodinium zambiense n. sp., and Metadinium ossiculi n. sp. In addition, Ostracodinium gracile form fissilaminatum Dogiel, 1932 was found for the second time and described as Metadinium fissilaminatum n. comb. The species composition was fairly unusual. Seven of the species have been found only in African wild antelopes and these species were found more frequently than cosmopolitan species. There was no evidence of isotrichid species. The average density of ciliates per 1 ml of the rumen fluid was 25.7 x 10(4), and the number of ciliate species per head of host was 10.8. PMID- 1522539 TI - Acanthamoeba healyi n. sp. and the isoenzyme and immunoblot profiles of Acanthamoeba spp., groups 1 and 3. AB - Two strains of Acanthamoeba isolated from human brain tissue and a strain of Acanthamoeba isolated from a fish were compared with 10 species of Acanthamoeba belonging to groups 1, 2 and 3 based on their isoenzyme profiles and antigenic characteristics. A total of 12 enzymes were studied. The isoenzymes and antigens were electrophoretically separated on polyacrylamide gradient gels, and the patterns obtained were compared after appropriate staining for particular enzymes and reactivities with homologous and heterologous rabbit anti-Acanthamoeba antisera. One of the human strains (CDC:1283:V013) was identified as A. healyi n. sp. because of its unique isoenzyme profiles for 11 of the 12 enzymes tested. The other human isolate was reidentified as A. culbertsoni because its isoenzyme profiles for 10 of 12 enzymes resembled those of A. culbertsoni, Lilly A-1 strain. Since the isoenzyme profiles and the antigenic patterns of the fish isolate as well were remarkably similar to those of A. royreba, it was considered as a strain of A. royreba. Polyacrylamide gradient gel electrophoresis appears to be a powerful technique for the study of isoenzymes and antigens of Acanthamoeba. PMID- 1522540 TI - Production and characterization of three polyclonal antibodies raised against cyst wall proteins of a hypotrichous ciliate. AB - Three polyclonal antibodies raised against Paraurostyla sp. cyst wall polypeptides of molecular weight 110,000 (p110), 66,000 (p66) and 52,000 (p52) have been obtained. The specificity of the antisera was tested by immunoblotting. Anti-p110 antibody detected five bands of 300, 170, 135, 110 and 40 kDa, respectively. Antiserum obtained against p66 recognized only this protein. Anti p52 antiserum showed reaction for two different bands of 52 and 44 kDa, respectively. The precise localization of these proteins in the cyst wall was assessed by light microscope immunocytochemistry. Anti-p110 antiserum produced a strong positive reaction in both the ectocyst and endocyst. Both anti-p66 and anti-p52 antibodies recognized the ectocyst. PMID- 1522541 TI - Plasmodium falciparum: differential sensitivity in vitro to E-64 (cysteine protease inhibitor) and Pepstatin A (aspartyl protease inhibitor). AB - We investigated the effect of a cysteine proteinase inhibitor (E-64) and an aspartyl proteinase inhibitor (Pepstatin A) on asexual erythrocytic stages of Plasmodium falciparum in culture. These two protease inhibitors showed different patterns of activity. E-64 acted preferentially against trophozoite and schizont stages. After 48 h incubation at high concentrations of E-64 (28, 140, 280 microM), growth was totally abolished and the parasites presented characteristic enlarged food vacuoles. Morphological alterations were also seen after shorter incubation periods (6 h at 28 microM) or 12 h at the inhibitory concentration 50% (12 microM), but an additional culture period (24 h) in inhibitor-free medium allowed normal parasite development, demonstrating a parasitostatic effect. E-64 acts on parasite multiplication; the normal merozoite maturation was altered and the normal reinvasion process partially impaired. Pepstatin A used at the inhibitory concentration 50% (4 microM) killed the parasites before trophozoite development and had a major effect on schizonts maturation. No altered parasite development occurred during an additional culture period without Pepstatin A, demonstrating a parasiticidal effect. E-64 and Pepstatin A used in combination inhibit the parasite growth with a strong synergistic effect. PMID- 1522542 TI - Continuous cultivation and drug susceptibility testing of Plasmodium falciparum in a malaria endemic area. AB - Isolates (UCH-23 and OM) and cloned strains of Plasmodium falciparum (Clones W-2 and D-6) were maintained in continuous culture for 28 to 150 days using culture media supplemented with 10% (v/v) heat inactivated semi-immune human plasma. Microscopic appearance and growth rates (R) of the parasites in media supplemented with semi-immune human plasma [R = 1.13 (W-2), 0.92 (D-6), 0.75 (OM) and 0.84 (UCH-23)] were comparable to those of parallel cultures maintained in media supplemented with 10% (v/v) heat inactivated non-immune human plasma [R = 1.42 (W-2), 0.83 (D-6), 0.66 (OM) and 0.89 (UCH-23)]. In addition, IC50 for chloroquine and mefloquine against the two cloned strains of P. falciparum maintained in culture media supplemented with either non-immune human plasma or semi-immune human plasma were identical. Although growth rates of new isolates (UCH-23 and OM) fluctuated over time, they stabilized between the 12th and 19th day of adaptation to culture. This fluctuation in growth rates of the new isolates underscores the influence of population dynamics during adaptation of P. falciparum to continuous culture. Sixty-eight percent of the primary isolates (170 of 250) obtained from patients in Ibadan were successfully adapted and maintained in continuous culture using semi-immune human plasma. The results of these studies indicate that semi-immune human plasma is a suitable supplement for continuous cultivation and drug susceptibility testing of P. falciparum.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1522543 TI - Amphotericin B-induced carbohydrate changes on the Trypanosoma cruzi surface membrane. AB - Changes in the cell surface carbohydrates of Trypanosoma cruzi epimastigotes induced by Amphotericin B (AmB) were assessed by chemical methods and by agglutination assay employing a panel of highly purified lectins of various sugar specificities. Escherichia coli K12 with mannose-sensitive fimbriae was also used as an agglutination probe. Amphotericin B caused a decrease in the total carbohydrate content of all glycoconjugate fractions isolated. Exposure to AmB strongly affected the mannose/galactose ratio (1:5) in the CHCl3/methanol/H2O soluble fraction. These sugars in 1.4:1 ratio were the major hexose components of control cells. The decrease in the mannose content (48 to 15%) after AmB treatment agrees with the marked decrease in the T. cruzi cell surface receptors for fimbriated E. coli K12. Also, an increase in the galactose content (74%) as compared with control cells (34%) is in agreement with the peanut agglutinin and Euonymus europaeus lectins agglutination results. Differences in the cell surface carbohydrates induced by AmB could be associated with alterations in the membrane structure and organization. PMID- 1522544 TI - Arginine catabolism by Leishmania donovani promastigotes. AB - Leishmania donovani promastigotes were grown to late log phase, washed and resuspended in iso-osmotic buffer containing L-arginine, and the rate of urea formation was then measured under various conditions. Addition of glucose or mannose activated urea formation, whereas 2-deoxyglucose inhibited and 6 deoxyglucose had no effect. Addition of alanine or of alpha-aminoisobutyrate inhibited urea formation, alanine causing a greater inhibition than alpha aminoisobutyrate. Addition of leucine, proline, glycine, or lysine had no effect on urea formation. The presence of glutamate also increased the rate of urea formation from arginine, but to a lesser extent than did glucose. The presence of both glucose and alanine caused no net change in urea formation, whereas the inhibitory effect of alanine exceeded the activating effect of glutamate, so that a small inhibition in the rate of urea formation occurred in the presence of both alanine and glutamate. Cells grown to 3-day stationary phase had a markedly reduced rate of arginine catabolism to urea, but the activating effect of glucose and the inhibitory effect of alanine were qualitatively similar to their effects on late log phase cells. Addition of water to cells suspended in buffer also inhibited urea formation, but this appeared to be due primarily to the release of alanine caused by the hypo-osmotic stress. Addition of mannitol to cells suspended in buffer caused a small inhibition of arginine catabolism. Addition of dibutyrylcyclic AMP, 3',5'-cyclic GMP, phorbol myristic acid, or A23187 had no effect on the rate of urea formation from arginine.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1522545 TI - Trypanosoma brucei brucei: in vitro production of metacyclic forms. AB - An in vitro method has been established to obtain metacyclic form populations of Trypanosoma brucei brucei. Trypanosome populations containing more than 98% of metacyclic forms were obtained from cultures which were: 1) initiated with bloodstream forms in primary cultures in the presence of Microtus montanus embryonic fibroblast-like cells (feeder cell layers); 2) maintained in glucose free Eagle's minimum essential medium supplemented with 10 mM L-proline, 2 mM L glutamine and 20% (v/v) fetal bovine serum at 27 degrees C without medium change for five days; 3) subcultured in the absence of the feeder cell layers but in the presence of Cytodex 3 beads; 4) maintained for an additional nine days with medium changes on days 5, 8 and 11; and 5) harvested on day 14 by means of diethylaminoethyl cellulose column chromatography prior to the appearance of other infective forms. Most of the trypanosomes obtained under these conditions were morphologically similar to metacyclic forms derived from tsetse fly vectors, coated with variable surface glycoprotein and were infective for mice. In the primary cultures procyclic forms, epimastigotes and metacyclic forms appeared by day 8. When the duration of the subculture was prolonged to 17 days or more at 27 degrees C, the metacyclic forms decreased in number while short trypomastigotes, long slender epimastigotes, and long slender trypomastigotes increased in number. These forms in such long-term cultures also appeared in diethylaminoethyl cellulose-isolated populations along with metacyclic forms. PMID- 1522547 TI - Inter- and intrasyngenic variations of the hemoglobin components in Paramecium caudatum. AB - The ciliated protozoan Paramecium contains hemoglobin in heterogeneous monomeric forms. In particular, Paramecium caudatum is characterized by the presence of a major component called Hb10 and a basic component named bHb. We found that in P. caudatum both of these hemoglobin components show some variation according to stock. The types and distributions of these hemoglobin components were examined on 16 stocks in five different syngens and one stock in an unidentified syngen using high performance liquid chromatography. The results indicate that in a variety of stocks the major component, Hb10, was divided into three types, A, B or A + B, and that the basic hemoglobin component was composed of a combination of two or three variants out of four possible, i.e. bHb 1, bHb 2, bHb 3 and bHb 4. Neither the Hb10 types nor the bHb variants, however, could be used to distinguish syngen in P. caudatum, since all of the Hb10 types and bHb variants were widely distributed over syngens and identical profiles appeared to some stocks in different syngens. PMID- 1522546 TI - Exceptions to mutual exclusion among cell surface i-antigens of Tetrahymena thermophila during salt stress and stationary phase. AB - In ciliates, only one of the alternative forms of the immunodominant membrane glycoprotein usually coats the external surface of the cell. Such mutual exclusion is regulated at the pretranslational level by mechanisms that result in the expression of a single protein gene. In the holotrich Tetrahymena thermophila five alternative cell surface immobilization proteins (i-antigens) are expressed under different conditions of temperature (L, H, T) and culture media (I, S). Using polyclonal and monoclonal antibodies to these proteins and a cDNA probe derived from the SerH3 gene, we have reinvestigated expression of i-antigens in media supplemented with 0.2 M NaCl. We find that in addition to S, the H and L antigens are also present on the cell surface. While all three i-antigens may be simultaneously present on the cell surface, the combinations S/L and S/H are more frequent. Compared to cells expressing H and L singly, the level of H3 mRNA is diminished, and a subset of the L family of polypeptides is variably expressed. The expression of S begins within 30 min after transfer to NaCl-supplemented medium, while the expression of L begins three days to several weeks after transfer. When cells are transferred out of NaCl-supplemented medium, S is turned off within 24 h, and L is expressed for at least 1 wk prior to the return of full H expression. Although these differences in kinetics suggest differences in control mechanism(s), the absence of I and T on the surface of NaCl-grown cells suggests that there is also a common regulatory link among H, S and L.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1522548 TI - Codon usage in Giardia lamblia. AB - A codon usage table for the intestinal parasite Giardia lamblia was generated by analysis of the nucleotide sequences of eight genes comprising 3,135 codons. Codon usage revealed a biased use of synonymous codons with a preference for NNC codons (42.1%). The codon usage of G. lamblia more closely resembles that of the prokaryote Halobacterium halobium (correlation coefficient r = 0.73) rather than that of other eukaryotic protozoans, i.e. Trypanosoma brucei (r = 0.434) and Plasmodium falciparum (r = -0.31). These observations are consistent with the view that G. lamblia represents the first line of descent from the ancestral cells that first took on eukaryotic features. PMID- 1522549 TI - Eimerians in harvest mice, Reithrodontomys spp., from Mexico, California and New Mexico, and phenotypic plasticity in oocysts of Eimeria arizonensis. AB - Between May 1979 and August 1991, 48.7% (57/117) of the harvest mice (Reithrodontomys spp.) examined from 10 localities in Mexico, California and New Mexico had coccidian oocysts in their feces. A total of 46.7% (49/105) of the Reithrodontomys megalotis examined were positive for coccidian oocysts; this included samples from five states in Mexico (47.1%, 8/17), three counties in California (66.7%, 4/6) and two counties in New Mexico (45.1%, 37/82); 66.7% (8/12) of the Reithrodontomys montanus from one county in New Mexico also were infected. Only two coccidian species, Eimeria arizonensis and Eimeria langebarteli, were found in these hosts. Oocysts of E. langebarteli were found only in R. megalotis: in all three infected mice from Madera County, California, in the only mouse from San Bernardino County, California, and in 63% (5/8) of the infected mice from four states in Mexico. Oocysts of E. arizonensis were found in R. megalotis in Mexico, California, and New Mexico and in R. montanus from New Mexico. Sporulated oocysts of E. langebarteli differed slightly from those in previously published reports by having wider oocysts and larger sporocysts. Sporulated oocysts of E. arizonensis were variable in size, with those recovered from R. montanus significantly larger in length and width and sporocyst width than those from R. megalotis. The structure of the oocyst residuum was polymorphic, both within and between host species, and within the same mouse; it could appear as one large globule, two globules, several to many smaller globules, or as a compact mass of many small granules. Oocysts with a variable residuum were larger than those with one globule in all oocyst/sporocyst dimensions.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1522550 TI - Unusual selective immunoglobulin deficiency in an Arabian foal. AB - A 10-month-old Arabian foal was evaluated for a suspected immunoglobulin (Ig) M deficiency. Decreased to nondetectable concentrations of IgM, IgA, and IgG (T), and a normal concentration of IgG, were present. Results of in vitro testing of the blood lymphocyte blastogenesis showed a weak response to the B-cell mitogen, lipopolysaccharide (LPS), but normal responses to T-cell mitogens. Results of postmortem examination showed synovitis of the left tibiotarsal and both scapulohumeral joints. Atrophy and edema of the lymph nodes and lymphocyte depletion in the thymus and spleen were seen. A subacute inflammatory infiltrate was observed in the kidney, synovium, liver, and brain. Etiologic agents were not identified. This case represents a previously unreported form of immunodeficiency disease in the horse. PMID- 1522551 TI - Immunosuppressive therapy in the treatment of immune-mediated disease. AB - Immune-mediated diseases represent some of the most frustrating types of disorders that are diagnosed and treated in veterinary medicine. Drug-induced immunosuppression is an attempt to control the aberrant immune response against self antigens but the immunosuppression can result in sepsis or other unacceptable adverse effects. If the pathophysiology of immune-mediated and autoimmune disease is considered, the immune response can be divided into several components and attempts can be made to selectively deal with each component separately. The components of the immune response that can be manipulated by therapy include antibodies, effector cells, the mononuclear phagocytic system, and the peripheral manifestations of disease. This article reviews the therapy of immune-mediated and autoimmune diseases based on a pathophysiologic approach and discusses conventional as well as current therapies in the treatment of these devastating diseases. PMID- 1522552 TI - Effect of breed and body weight on echocardiographic values in four breeds of dogs of differing somatotype. AB - Eighty normal dogs of four morphologically disparate breeds (Pembroke Welsh Corgi, Miniature Poodle, Afghan Hound, Golden Retriever) (twenty of each breed), were studied by echocardiography to determine the importance of breed and weight in establishing normal echocardiographic reference ranges. Echocardiographic measurements included left-ventricular chamber dimension at systole and end diastole, right-ventricular chamber dimension at end-diastole, interventricular septal thickness at systole and end-diastole, left-ventricular free wall thickness at systole and end-diastole, E-point septal separation, aortic root dimension at end-diastole, left atrial dimension, and fractional shortening. Analyses of covariance indicated that for all measurements except right ventricular chamber dimension, the means were significantly different among breeds, after the differences in weight were taken into account. Echocardiographic measurements are variable even within the same breed. Breed must be considered in establishing echocardiographic measurement reference ranges. Echocardiographic values for each breed are presented. PMID- 1522553 TI - Differentiation of chronic lymphocytic leukemia in the horse. A report of two cases. AB - Chronic lymphocytic leukemia (CLL) was diagnosed in two horses: an 18-year-old Quarter Horse gelding that was examined because of edema of the prepuce and ventral abdomen; and a 20-year-old mixed breed gelding that was referred because of lymphocytosis, ventral edema, and weight loss. The first horse had enlarged peripheral lymph nodes and cool nonpainful pitting edema of the ventral abdomen and prepuce. The second horse had enlarged peripheral lymph nodes, cool nonpainful pitting edema of the ventral thorax and cranial ventral abdomen, and a 3/5 holosystolic heart murmur. The diagnosis of CLL was based on increased blood lymphocyte counts and infiltration of marrow and other tissues by lymphocytes. In horse 1, the lymphocytosis persisted for 2 months between initial examination and death. The results of flow cytometric analysis on blood lymphocytes using anti lymphocyte antibodies suggested that horse 1 had T-cell CLL, and horse 2 had B cell CLL. In addition, the second horse had a monoclonal gammopathy (IgG), with light-chain proteinuria. PMID- 1522554 TI - Evaluation of L-asparaginase: polyethylene glycol conjugate versus native L asparaginase combined with chemotherapy. A randomized double-blind study in canine lymphoma. AB - L-asparaginase is an enzyme that inhibits protein synthesis by the depletion of sources of L-asparagine, which is necessary for transformed lymphoid cells to proliferate. L-asparaginase is used in the treatment of childhood acute lymphoblastic leukemia. A problem with L-asparaginase therapy is the immunogenicity of the enzyme and the development of anaphylactic reactions. Canine lymphoma is a predominantly B-cell tumor with widespread disease; without treatment, dogs with lymphoma usually survive 1-2 months. Canine lymphoma will respond to L-asparaginase therapy. A randomized double-blind study evaluated a polyethylene glycol (PEG) conjugate L-asparaginase combined with chemotherapy (vincristine, cyclophosphamide, doxorubicin, and prednisone). Thirty-five dogs were randomized to the PEG L-asparaginase group, and 34 dogs were randomized to the native L-asparaginase group. Thirty dogs (85.7%) achieved a complete remission (CR) with a median time to relapse of 217 days, and 32 (94.1%) dogs in the native L-asparaginase group achieved a CR with a median time to relapse of 214 days (P greater than 0.05). The asparaginase was well tolerated in both groups. Two dogs in the native L-asparaginase group had severe allergic reactions, and one dog in the PEG asparaginase group had a generalized urticarial reaction after repeated injections. This study indicates that PEG L-asparaginase has equal therapeutic efficacy to native L-asparaginase. PMID- 1522555 TI - Canine leptospirosis. A retrospective study of 17 cases. AB - Seventeen dogs were diagnosed with leptospirosis on the basis of clinical findings, laboratory abnormalities, and serology. This article summarizes and characterizes the historical and physical findings, laboratory data, serology, treatment, and outcome of these dogs. All of the dogs had serologic evidence of infection with interrogans serovars pomona and grippotyphosa. These findings are compared with previous reports of canine infection with Leptospira interrogans serovars icteroaemorrhagiae and canicola. The clinical presentation of these dogs did not correspond to the classic description of the disease in dogs in which concurrent renal and hepatic diseases are present. This may be due to infection with different serovars than those previously reported. In addition, this article suggests that canine leptospirosis should be considered in the differential diagnosis of dogs with acute or subacute renal failure. PMID- 1522557 TI - Single coronary artery (type R2A) PMID- 1522556 TI - Phase I evaluation of doxorubicin and whole-body hyperthermia in dogs with lymphoma. AB - Fifteen previously untreated dogs with histologically confirmed, high-grade multicentric lymphoma were entered into a phase I study to evaluate combined doxorubicin and whole-body hyperthermia (DOX/WBH). Groups of three, four, and eight dogs were treated with whole-body hyperthermia and concurrent doxorubicin at 12 mg/m2, 24 mg/m2 and 30 mg/m2, respectively, after one doxorubicin induction dose at 30 mg/m2. Plateau temperature (42 +/- 0.1 degree C) was maintained for 90 minutes using a radiant heating device. A total of five DOX/WBH treatments per dog were planned, and these were given every 21 days. Treatment-related toxicity was not seen in the 12-mg/m2 doxorubicin dose group. Tumor progression prohibited administration of more than three DOX/WBH treatments to any dog in the 12-mg/m2 group. Premature ventricular contractions developed after the fifth treatment in one of the four dogs treated with 24 mg/m2 of doxorubicin. Two dogs (25%) in the 30-mg/m2 dose group had treatment-related toxicity. One dog experienced acute serious myelosuppression 1 week after the third treatment. This dog received all planned DOX/WBH treatments. Asymptomatic cardiac toxicosis consisting of decreased ejection fraction and fractional shortening developed in the second dog. This dog received only two DOX/WBH treatments. The three dogs treated at 12 mg/m2 had partial responses of short duration (60-83 days). Four dogs treated at 24 mg/m2 had complete responses for 150, 164, 186, and 200 days. Eight dogs treated at 30 mg/m2 had complete responses with a mean and median duration of 241 and 190 days, respectively.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1522558 TI - Ontogeny of immunosuppressive activity, MHC antigens and leukocytes in the rat testis. AB - The levels of immunosuppressive activity and the presence of MHC antigens and leukocytes were studied in the immature and the sexually mature rat testis. The immunosuppressive activities were measured from high-molecular weight (greater than 5 kDa) fractions of testis extracts using the protectin bioassay. The presence of MHC antigens and leucocytes was studied using the indirect immunoperoxidase method. In the immature rats, clusters of class I MHC antigen positive cells and a few cells expressing class II MHC antigen were present in the testicular interstitium. In the sexually mature rats, all the cells were MHC I+, and MHC II+ cells were numerous in the testicular interstitium. The seminiferous epithelium was MHC-negative in both the immature and the sexually mature testis. W3/25+ leukocytes were present in the interstitium and the tubular wall in both the immature and the sexually mature rat testis, but not in the seminiferous epithelium at any age. At 20-30 days of age, the testicular extracts were neutral or slightly stimulated 3H-TdR incorporation into peripheral blood lymphocytes, but at 44-60 days of age they inhibited lymphocyte proliferation significantly. In gel filtration, a peak of immunosuppressive activity was observed at approximately 400 kDa (protectin A) in both 20- and 60-days-old rat testes. A smaller peak was present at approximately 200 kDa in both age groups. This study shows that the testicular immunoregulatory microenvironment is different in the immature and the sexually mature rats. This may be important in such age-dependent human diseases as mumps orchitis and the testicular relapses of acute lymphoblastic leukemia. PMID- 1522559 TI - Isolation of a phylogenetically conserved and testis-specific gene using a monoclonal antibody against the serological H-Y antigen. AB - Several cDNA clones of a gene termed male-enhanced antigen-2 (Mea-2), have been isolated from a mouse testicular expression cDNA library using a monoclonal histocompatability Y (H-Ys) antibody which detects specific protein(s) present in the mouse testis but not the ovary. The Mea-2 gene is phylogenetically conserved among various mammalian species examined, and is expressed at high levels in adult mouse testis. The expression pattern of Mea-2 is very similar to that of another gene, the male-enhanced antigen-1 (Mea-1), previously isolated using a polyclonal H-Ys antibody. Northern blotting and RT-PCR analyses demonstrated that Mea-2 is also expressed in other adult and fetal mouse organs at low levels. The testis-enhanced expression of this gene is associated with germ cell development at mid- to late-meiotic stages of spermatogenesis. Analysis of an intersubspecies mouse backcross has assigned this gene to chromosome 5, between the loci Gus and Hnf-1. PMID- 1522560 TI - Proacrosin binding protein: immunocomparative studies in boar, bovine, hamster, human and ram. AB - The cross reactivities of acidic extracts from boar, bovine, hamster, human and ram spermatozoa to a polyclonal antibody of the boar proacrosin binding protein has been investigated. The pH 3.0 extracts of the washed spermatozoa from each species were subjected to Western blot analysis using a polyclonal antibody developed against the 28 kDa boar proacrosin binding protein. The boar sperm extracts had a major 28 kD and a minor 29 kDa proacrosin binding protein. A similar protein of 29 kDa was present in the bovine and ram samples, while the hamster had bands at 22 and 25 kDa. Extracts of human sperm yielded a diffuse but distinct area of cross reactivity of about 25-30 kDa. These results demonstrate that proacrosin binding proteins are present in sperm of different mammalian species and they have similar molecular weights. PMID- 1522561 TI - Monoclonal antiphospholipid antibody reactivity against human placental trophoblast. AB - Naturally occurring antibodies against the negatively charged phospholipids cardiolipin (CL) and phosphatidylserine (PS) have been associated with recurrent pregnancy loss. One prevalent hypothesis proposes that antiphospholipid antibody (aPL) mediated pathophysiology is through increased placental thrombosis. In this study we investigated the reactivity of three mouse monoclonal aPLs with term and 26 week human placental preparations. Each monoclonal antibody reacted differently with CL and PS; 3SB9b reacted with PS (CL-/PS+), D11A4 reacted with CL (CL+/PS-) and BA3B5C4 reacted with both CL and PS (CL+/PS+). 3SB9b reacted strongly with the syncytiotrophoblastic layer of both formalin fixed and frozen placental tissue. Sporadic reactivity was observed against the cytotrophoblastic layer. BA3B5C4 reacted strongly and specifically with cytotrophoblastic cells. D11A4 had only weak reactivity in the subtrophoblastic stromal region of the placenta in frozen sections. aPL staining was also observed against extravillous cytotrophoblast. BA3B5C4 stained cytoplasmic structures, whereas 3SB9b stained the plasma membrane region with little cytoplasmic staining. These data suggest that the trophoblastic layer is reactive with aPLs and may potentially be directly damaged through mechanisms unrelated to thrombosis. In addition, the trophoblastic layer directly in contact with the maternal circulation is most reactive with aPLs that are PS+ rather than CL+. The differential reactivity of 3SB9b and BA3B5C4 suggests that the antigenic conformation involving PS on the cytotrophoblast is altered concurrent with fusion into the syncytium. PMID- 1522562 TI - Autoantibodies in women with primary recurrent spontaneous abortion of unknown etiology. AB - A group of 153 women with 3 or more recurrent spontaneous abortions (RSAs) with unknown etiology and 90 normal multigravida controls were evaluated for antibodies to phospholipids and nuclear antigens. We demonstrate that women with recurrent spontaneous abortions showed significantly higher incidence of antibodies to phospholipids than normal multigravida controls. In contrast, the incidence of antibodies to polynucleotides and histones was not different between these two groups. These findings suggest that antiphospholipid antibodies are either epiphenomena or causally related to recurrent spontaneous abortions. PMID- 1522563 TI - Effect of sperm-associated antibodies on the dynamics of sperm movement and on the acrosome reaction of human spermatozoa. AB - Anti-sperm antibodies were eluted from the sperm cell fraction of autoimmune human ejaculates and transferred onto normal motile spermatozoa. The movement and the acrosomal status of these antibody-coated spermatozoa were evaluated after incubation in a capacitating medium. The amplitude of lateral head displacement (ALH) and the straight line velocity (VSL) were analyzed using an HTM automated motility analyser. Acrosomal loss was monitored by an FITC-conjugated lectin binding technique. During the 6-h incubation in BWW-BSA medium, antibody-free and antibody-coated spermatozoa exhibited significant changes of ALH and VSL distribution that evolved differently in the two populations. The dynamics of sperm movement in control spermatozoa were apparently modified by the presence of antibodies on the sperm membrane. The low percentage of spontaneous acrosomal loss obtained in control populations, even after 20 h of incubation, was not modified by the presence of antibodies on spermatozoa. However, the same antibodies decreased the acrosomal loss induced by a calcium ionophore after 3 h of incubation in capacitating conditions. These results suggest that sperm capacitation and acrosome reaction, considered as essential for successful fertilization, can be altered by antisperm antibodies present on human ejaculated spermatozoa. PMID- 1522564 TI - Secretory immune system of the male reproductive tract: effects of dihydrotestosterone and estradiol on IgA and secretory component levels. AB - Immunoglobulin A (IgA) is present at mucosal sites of the body which are exposed to the external environment. In this study we evaluated the levels of IgA and its transport protein secretory component (SC) in organs of the male reproductive tract of both intact and castrate-hormone-treated rats. Our goals were to determine whether these proteins are present in the male reproductive tract and whether sex hormones can influence the amounts of IgA and SC in selected organs. We found that in intact animals, IgA was present in the prostate, epididymis, vas deferens and testis and that SC levels in the prostate were 22-fold greater than in these same organs. Dihydrotestosterone (DHT) and/or estradiol, when administered to castrate animals, dramatically increased the levels of prostatic SC. In contrast, the levels of IgA were only minimally affected. DHT administration also resulted in a significant increase in SC found in the seminal vesicles. These studies demonstrate that IgA and SC are present in the male reproductive tract of the rat. Further, they show that androgens and estrogens act at selected sites in the male reproductive tract to play an important role in maintaining SC levels and thereby suggest that these hormones influence the movement of IgA from tissues into secretions. PMID- 1522565 TI - Biological actions of monoclonal antibodies to bovine lutropin receptor. AB - Monoclonal antibodies (Mabs) were produced against bovine Lutropin receptor (LH R). Antibodies were detected by an enzyme linked immunosorbant assay (ELISA). Hybridomas were subcloned to achieve monoclonality. Ascites were developed in Balb/c mice. Hybridoma supernatants were purified by ammonium sulfate precipitation and chromatography on hydroxylapatite columns. LH-R antibodies showed upto 50% inhibition of 125I-labeled hCG binding to bovine luteal cell membranes and up to 80% inhibition of testosterone production by hCG stimulated mouse Leydig cells. LH-R antibodies were predominantly IgM isotype. Purified antibodies showed a 78-kDa band, in SDS-PAGE, as the heavy chain of the immunoglobulin. LH-R antibodies were localized specifically in the thecal and luteal cells of the rat ovaries as well as in the Leydig cell of mouse testes. Injections of the LH-R antibody caused a constant estrus in normal rats. One month after the cessation of the injections the animals returned to normal estrus cycle and fertility. Pregnant mice injected with LH-R antibodies produced only 3 viable pregnancies and 10 pups, as compared to 8 pregnancies and 45 pups born to normal controls. LH-R antibodies also caused, approximately, a 50% reduction in testosterone production in normal male rats. These observations indicate a high degree of specificity of the Mab to LH-R and their potential in studies on gonadal function. PMID- 1522566 TI - Tissue reconstruction with nonpenetrating arcuate-legged clips. Potential endoscopic applications. AB - A new system for tissue approximation consisting of a nonpenetrating arcuate legged clip applied to everted tissue edges to form an elastomeric flanged joint is described. The flanged joint has unusual physical and morphologic properties. Novel systems for tissue eversion, clip application and clip removal have been tested at the micro scale in blood vessels and the rat vas deferens (vasovasostomy). Human applications have been successful (cerebrovascular reconstruction, free-flap transfer, skin grafting, A-V access). The system is biologically and technically equivalent to or superior to the needle-and-suture technique. Avoidance of intimal or mucosal penetration or intraluminal foreign body is associated with prompt wound healing and the reconstitution of tubular integrity. The system is readily adaptable for endoscopic surgical reconstructions, providing the surgeon with enhanced reconstructive abilities. PMID- 1522567 TI - Endometrial ablation. Improvement in PMS related to the decrease in bleeding. AB - Of 108 patients evaluated before and after ablation of the endometrium since July 1986, for menorrhagia and symptoms associated with the menstrual period, 57 met criteria for premenstrual syndrome (PMS). An additional 35 patients had symptoms associated with their menstrual period but did not qualify for a diagnosis of PMS. Following endometrial ablation most patients in both groups reported either amenorrhea or spotting and decreased severity of symptoms. The degree of improvement in both PMS and perimenstrual symptoms seemed to be related to the degree to which bleeding was reduced. PMID- 1522569 TI - Ectopic pregnancy following the treatment of tubal infertility. AB - To evaluate the prognosis for the patient who becomes pregnant after infertility treatment, we analyzed the occurrence of ectopic pregnancy following reconstructive surgery and in vitro fertilization/embryo transfer (IVF/ET) for tubal infertility. The results of 474 microsurgical operations and the results of 2,119 stimulated IVF/ET cycles for tubal infertility in the Reproduction Unit of Ljubljana University Department of Obstetrics and Gynecology are presented. The ratio of patients who subsequently had only ectopic pregnancies to the number of operations was 12%. Ectopic pregnancies represented 28% of all pregnancies after surgery. In IVF/ET cycles for tubal infertility, ectopic pregnancy represented 2.8% of all pregnancies and 3 permiles of all transfers. There was one (0.5%) heterotopic pregnancy. The likelihood of live births (30%, one or more times) after surgery compensates the high risk for ectopic pregnancy. While the risk for ectopic pregnancy after IVF/ET is much lower than the risk after tubal surgery, it is still rather high compared with the risk in the normal population. In the cases with severe tubal lesions IVF/ET is preferable to tubal surgery. The results show the importance of considering ectopics when deciding upon treatment and in patients who become pregnant after treatment for tubal infertility. PMID- 1522568 TI - Analysis of tissue margins of cone biopsy specimens obtained with "cold knife," CO2 and Nd:YAG lasers and a radiofrequency surgical unit. AB - Analysis of the tissue margins of cone biopsy specimens obtained from 40 patients showed varying degrees of thermal and mechanical artifact at the tissue margins. The least artifact was seen in the tissue margins of specimens obtained with the scalpel ("cold knife"). The amount of thermal damage to biopsies obtained via lasers and the radiofrequency unit varied with the instrument employed. However, the quality of the tissue margins of specimens obtained using a radiofrequency surgical unit equipped with a needle electrode on a "pure cut" setting approached the quality of those obtained with the cold knife in their lack of thermal and mechanical artifact. PMID- 1522570 TI - Correlation of focal pelvic tenderness with implant dimension and stage of endometriosis. AB - Reported symptoms in patients with endometriosis have shown poor correlation with the extent of disease at surgery. Recent data have suggested that signs and symptoms may correlate with depth and volume of individual implants. In this study preoperative focal tenderness was correlated with the presence or absence of endometriosis, depth and volume of the endometrial implants and the presence of other pathology. The findings suggest that focal tenderness has limited value in predicting the stage of endometriosis, but is strongly associated with the presence of disease in the cul de sac and uterosacral ligaments. There was also significant association of tenderness with deeper and larger volumes of implants, a finding that may be of clinical significance in the surgical management of endometriosis-associated symptoms and tenderness. PMID- 1522571 TI - Endometrial ablation repeat procedures. Case studies. AB - Of 143 women who underwent endometrial ablation from May 1986 through August 1991, 16 requested repeat endometrial ablation and 7 underwent hysterectomy. Only two of the hysterectomies were performed for bleeding, and no hysterectomy was needed for any woman who had a repeat endometrial ablation. For patients undergoing one ablation, the results were amenorrhea in 55 women (38%), staining in 32 (22%), light flow in 33 (23%), 7 hysterectomies (5%) and 16 patients requesting repeat endometrial ablation (11%). Repeat endometrial ablation resulted in amenorrhea in 10 women (63%), staining in 3 (19%) and light flow in 3 (19%). Repeat endometrial ablation can eliminate the need for hysterectomy in women who continue to have bleeding problems after one endometrial ablation. Gynecologists should not hesitate to offer repeat ablation since the results will usually be excellent. PMID- 1522572 TI - Fatal fetal abnormalities. Route of delivery and effect of the development of antepartum diagnostics in the last 13 years. AB - The appropriateness of cesarean section as the route of delivery in pregnancies complicated by fatal fetal abnormalities was evaluated in an obstetric population of 47,924 deliveries during the years 1978-90. The incidence of fatal fetal abnormalities was 0.50% and did not change during the study period. The cesarean section rate was twice that in the whole obstetric population, and the procedure was performed mainly for inappropriate fetal indications. One-third of the sections were caused by antepartum or intrapartum fetal distress. After the advent of sophisticated real-time ultrasound equipment, the obstetric management of those cases seemed to increase, but later the incidence of cesarean sections for fetal indications decreased, from increased experience with assessing the prognosis of malformed fetuses and increased opportunities to examine the fetal karyotype. Some conservatism seems justified when choosing obstetric management of a malformed fetus before large, controlled, clinical studies become available. PMID- 1522573 TI - Identifying the obstetric patient at high risk of multiple-unit blood transfusions. AB - We sought to characterize the obstetric patient who required more than the 1 or 2 units of blood products typically available by autologous donation. Medical records from 1988 were reviewed retrospectively. During this period, 16,462 deliveries were performed. Twenty-seven patients (0.16%) received more than 2 units of blood products during their pregnancies. The most common diagnoses associated with a transfusion were placenta previa (10), uterine atony (8) and abruption (5). Platelets, fresh frozen plasma and cryoprecipitate were administered to 7, 12 and 4 patients, respectively. An antepartum condition associated with hemorrhage was identified in only 11 of the 27 patients (41%) who received greater than or equal to 3 units of blood products. The remainder of the cases were not diagnosed during the antepartum period, when autologous donation is an option. PMID- 1522574 TI - Snake bite poisoning in pregnancy. A review of the literature. AB - With our 2 cases, there are 30 reported cases in English of snake bite poisoning in pregnancy with some details presented and 20 cases without details, for a total of 50 cases. We reviewed the maternal and fetal outcomes in the 30 cases that had such information. Poisoning by members of the Crotalidae family (rattlesnakes, cotton-mouths [water moccasins] and copperheads) during pregnancy carries with it a fetal wastage rate of 43% and a maternal mortality rate of 10%. Pit viper bites cause a bleeding diathesis from the fact that the venom of these snakes contains a procoagulant that defibrinates the blood and leads to bleeding throughout the body. PMID- 1522575 TI - Oral methotrexate for persistent ectopic pregnancy. A case report. AB - Persistent ectopic pregnancy complicates a significant percentage of conservative tubal pregnancy procedures. The optimal treatment of persistent trophoblast has yet to be determined. Most reported cases have been treated by reoperation and removal of the affected tube. Use of methotrexate may avoid the need for reoperation and permit tubal salvage. We report on a case of persistent ectopic pregnancy treated successfully using an oral methotrexate regimen originally described for treating nonmetastatic gestational trophoblastic neoplasia. Oral methotrexate provides a simple, convenient, outpatient treatment option for cases of persistent ectopic pregnancy diagnosed by a rise or plateau in human chorionic gonadotropin levels following conservative surgery. PMID- 1522577 TI - Relationship of anterior cruciate ligament injury to notch width index (a roentgenographic study). PMID- 1522576 TI - The University of Mississippi Medical Center In Vitro Fertilization Program: 1984 1991. PMID- 1522578 TI - Medicaid income can be tax-deferred. PMID- 1522579 TI - "Contact your doctor for a prescription". PMID- 1522580 TI - Opinions on social policy issues. PMID- 1522581 TI - Structure of tobraviral particles: a model suggested from sequence conservation in tobraviral and tobamoviral coat proteins. AB - Comparisons of the coat protein sequences of four tobraviruses with those of seven tobamoviruses indicate that these proteins share a common evolutionary origin. Numerous amino acids for which specific functions have been identified in the molecular structure of the tobacco mosaic virus vulgare protein have identical or closely similar counterparts among the tobraviral proteins. These include those with roles in the hydrophobic core of the protein, those that contribute to the RNA binding site and those involved in the control of virus assembly. We suggest a model for the structure of the tobraviral particle that not only offers an explanation for the greater diameter of the tobraviral particle but also confirms an early suggestion for RNA placement within this particle. PMID- 1522582 TI - G+C-rich tract in 5' end of human introns. AB - Analysis of an artificial neural network trained to classify DNA as coding or non coding revealed compositional differences between sequence parts translated into protein and those that were not. The 5' end of human introns was found to have a base composition that was non-random to an extent matching the non-randomness in the 3' end that contains the polypyrimidine tract. The prevailing nucleotides in the initial 50 nucleotides of human introns are guanine and cytosine, the trinucleotide GGG was found to occur almost four times as frequently as it would in sequences with a uniform distribution of the nucleotides. The initial part of terminal exons and their associated terminal introns were shown to have a very special base composition deviating strongly from the normal picture in other exons and introns. PMID- 1522583 TI - Structural organization of the genes encoding the small nuclear RNAs U1 to U6 of Tetrahymena thermophila is very similar to that of plant small nuclear RNA genes. AB - We report the sequences of the genes encoding the small nuclear RNAs (snRNAs) U1 to U6 of the ciliate Tetrahymena thermophila. The genes of the individual snRNAs exist in two to six slightly different copies per haploid genome. Sequence analyses of the gene-flanking regions indicate that there are two classes of snRNA genes. Both classes are characterized by several conserved sequence elements, some of which are unique to each class and some of which are found in both classes. Comparison of the promoter structure of the snRNA genes of T. thermophila with the promoter structures of snRNA genes of other organisms revealed several similarities to plant snRNA genes. These similarities include the overall promoter architecture as well as specific sequence elements. The structural organization of the 3' flanking region of some of the T. thermophila snRNA genes is not observed in other organisms. This finding is discussed in relation to a possible role in snRNA 3'-end formation. PMID- 1522584 TI - Crystal structures of two mutant neuraminidase-antibody complexes with amino acid substitutions in the interface. AB - The site on influenza virus N9 neuraminidase recognized by NC41 monoclonal antibody comprises 19 amino acid residues that are in direct contact with 17 residues on the antibody. Single sequence changes in some of the neuraminidase residues in the site markedly reduce antibody binding. However, two mutants have been found within the site, Ile368 to Arg and Asn329 to Asp selected by antibodies other than NC41, and these mutants bind NC41 antibody with only slightly reduced affinity. The three-dimensional structures of the two mutant N9 NC41 antibody complexes as derived from the wild-type complex are presented. Both structures show that some amino acid substitutions can be accommodated within an antigen-antibody interface by local structural rearrangements around the mutation site. In the Ile368 to Arg mutant complex, the side-chain of Arg368 is shifted by 2.9 A from its position in the uncomplexed mutant and a shift of 1.3 A in the position of the light chain residue HisL55 with respect to the wild-type complex is also observed. In the other mutant, the side-chain of Asp329 appears rotated by 150 degrees around C alpha-C beta with respect to the uncomplexed mutant, so that the carboxylate group is moved to the periphery of the antigen-antibody interface. The results provide a basis for understanding some of the potential structural effects of somatic hypermutation on antigen-antibody binding in those cases where the mutation in the antibody occurs at antigen-contacting residues, and demonstrate again the importance of structural context in evaluating the effect of amino acid substitutions on protein structure and function. PMID- 1522585 TI - Domain closure in mitochondrial aspartate aminotransferase. AB - The subunits of the dimeric enzyme aspartate aminotransferase have two domains: one large and one small. The active site lies in a cavity that is close to both the subunit interface and the interface between the two domains. On binding the substrate the domains close together. This closure completely buries the substrate in the active site and moves two arginine side-chains so they form salt bridges with carboxylate groups of the substrate. The salt bridges hold the substrate close to the pyridoxal 5'-phosphate cofactor and in the right position and orientation for the catalysis of the transamination reaction. We describe here the structural changes that produce the domain movements and the closure of the active site. Structural changes occur at the interface between the domains and within the small domain itself. On closure, the core of the small domain rotates by 13 degrees relative to the large domain. Two other regions of the small domain, which form part of the active site, move somewhat differently. A loop, residues 39 to 49, above the active site moves about 1 A less than the core of the small domain. A helix within the small domain forms the "door" of the active site. It moves with the core of the small domain and, in addition, shifts by 1.2 A, rotates by 10 degrees, and switches its first turn from the alpha to the 3(10) conformation. This results in the helix closing the active site. The domain movements are produced by a co-ordinated series of small changes. Within one subunit the polypeptide chain passes twice between the large and small domains. One link involves a peptide in an extended conformation. The second link is in the middle of a long helix that spans both domains. At the interface this helix is kinked and, on closure, the angle of the kink changes to accommodate the movement of the small domain. The interface between the domains is formed by 15 residues in the large domain packing against 12 residues in the small domain and the manner in which these residues pack is essentially the same in the open and closed structures. Domain movements involve changes in the main-chain and side chain torsion angles in the residues on both sides of the interface. Most of these changes are small; only a few side-chains switch to new conformations.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1522586 TI - Three-dimensional structure of class pi glutathione S-transferase from human placenta in complex with S-hexylglutathione at 2.8 A resolution. AB - The three-dimensional structure of human class pi glutathione S-transferase from placenta (hGSTP1-1), a homodimeric enzyme, has been solved by Patterson search methods and refined at 2.8 A resolution to a final crystallographic R-factor of 19.6% (8.0 to 2.8 A resolution). Subunit folding topology, subunit overall structure and subunit association closely resembles the structure of porcine class pi glutathione S-transferase. The binding site of a competitive inhibitor, S-hexylglutathione, is analyzed and the locations of the binding regions for glutathione (G-site) and electrophilic substrates (H-site) are determined. The specific interactions between protein and the inhibitor's glutathione peptide are the same as those observed between glutathione sulfonate and the porcine isozyme. The H-site is located adjacent to the G-site, with the hexyl moiety lying above a segment (residues 8 to 10) connecting strand beta 1 and helix alpha A where it is in hydrophobic contact with Tyr7, Phe8, Val10, Val35 and Tyr106. Catalytic models are discussed on the basis of the molecular structure. PMID- 1522587 TI - Topology fingerprint approach to the inverse protein folding problem. AB - We describe the most general solution to date of the problem of matching globular protein sequences to the appropriate three-dimensional structures. The screening template, against which sequences are tested, is provided by a protein "structural fingerprint" library based on the contact map and the buried/exposed pattern of residues. Then, a lattice Monte Carlo algorithm validates or dismisses the stability of the proposed fold. Examples of known structural similarities between proteins having weakly or unrelated sequences such as the globins and phycocyanins, the eight-member alpha/beta fold of triose phosphate isomerase and even a close structural equivalence between azurin and immunoglobulins are found. PMID- 1522588 TI - Structure of scorpion toxin variant-3 at 1.2 A resolution. AB - The crystal structure of the variant-3 protein neurotoxin from the scorpion Centruroides sculpturatus Ewing has been refined at 1.2 A resolution using restrained least-squares. The final model includes 492 non-hydrogen protein atoms, 453 protein hydrogen atoms, eight 2-methyl-2,4-pentanediol (MPD) solvent atoms, and 125 water oxygen atoms. The variant-3 protein model geometry deviates from ideal bond lengths by 0.024 A and from ideal angles by 3.6 degrees. The crystallographic R-factor for structure factors calculated from the final model is 0.192 for 17,706 unique reflections between 10.0 to 1.2 A. A comparison between the models of the initial 1.8 A and the 1.2 A refinement shows a new arrangement of the previously poorly defined residues 31 to 34. Multiple conformations are observed for four cysteine residues and an MPD oxygen atom. The electron density indicates that disulfide bonds between Cys12 and Cys65 and between Cys29 and Cys48 have two distinct side-chain conformations. A molecule of MPD bridges neighboring protein molecules in the crystal lattice, and both MPD enantiomers are present in the crystal. A total of 125 water molecules per molecule of protein are included in the final model with B-values ranging from 11 to 52 A2 and occupancies from unity down to 0.4. Comparisons between the 1.2 A and 1.8 A models, including the bound water structure and crystal packing contacts, are emphasized. PMID- 1522589 TI - Crystal structure of a chimeric Fab' fragment of an antibody binding tumour cells. AB - The crystal structure of a chimeric Fab' fragment of a monoclonal antibody is presented. The Fab' comprises the murine light chain and heavy chain variable domains of the carcinoma-binding antibody B72.3 fused to the constant domain of human kappa, and the first constant domain and hinge domain of human gamma 4, respectively. A model for the Fab' has been determined by molecular replacement and refined to a resolution of 3.1 A with an R-factor of 17.6%. The additional residues that distinguish a Fab' from a Fab fragment are seen to be disordered in the crystals. The H3 hypervariable loop is short and adopts a sharp hairpin turn in a conformation that results from an interaction between the lysine side-chain of H93 and the main-chain carbonyl group of H96. The remaining hypervariable loops display conformations similar to those predicted from the canonical structures approach, although loop H2 is apparently displaced by a salt-bridge formed between H55 Asp and the neighbouring H73 Lys. These and other features of the structure likely to be important in grafting the hypervariable loops to an otherwise human framework are discussed. PMID- 1522590 TI - Human liver cathepsin D. Purification, crystallization and preliminary X-ray diffraction analysis of a lysosomal enzyme. AB - The two-chain form of active cathepsin D, a glycosylated, lysosomal aspartic proteinase, has been isolated from human liver. Isoelectric focusing revealed two major species of enzyme that differed by approximately 0.2 pI unit. Crystals suitable for X-ray diffraction analysis were prepared from acidic solutions using precipitation with ammonium sulfate. The hexagonal crystals diffracted X-rays to beyond 3.1 A resolution and belonged to space group P6(1) (or P6(5)) with cell constants a = b = 125.9 A, c = 104.1 A, gamma = 120.0 degrees. The crystals likely contain two molecules in the asymmetric unit, giving a solvent content of 56% (v/w). Biochemical analysis of crystals indicated that both isoforms were present in approximately equimolar proportions. Full structure determination of the enzyme is underway. PMID- 1522591 TI - Human epidermal growth factor. High resolution solution structure and comparison with human transforming growth factor alpha. AB - The solution structure of the 53 amino acid peptide hormone, human epidermal growth factor (hEGF), has been determined to high resolution from nuclear magnetic resonance (n.m.r.) data. A large number of internuclear distance and dihedral restraints was obtained, including data from uniformly 15N-labelled hEGF. Dynamical simulated annealing methods using the program XPLOR were used for structure calculation. An improved protocol was developed combining efficient conformational searching at a reduced computational cost. The general fold of the calculated structures compared well with that of a derivative of the carboxy terminally truncated hEGF determined previously. A group of 44 structures were calculated with no violations greater than 0.3 A and 3 degrees for distance and dihedral restraints, respectively. The average pairwise root mean square (r.m.s.) deviation of all backbone atoms for these structures was 2.25 A for all 53 residues, 0.92 A for the bulk of the protein, and 0.23 A for the functionally important carboxy-terminal domain. Two new helical segments containing highly conserved amino acids have been identified; one between cysteines 6 and 14 and a second at the end of the carboxy-terminal domain. New insight into the molecular architecture of the site of putative receptor binding was provided by comparing the structure of hEGF with its biologically equipotent analogue, human transforming growth factor alpha. This comparison revealed a close structural relationship between the two growth factors and provides an improved understanding of the structure/function relationships in EGF. PMID- 1522592 TI - Crystal structure of glycinamide ribonucleotide transformylase from Escherichia coli at 3.0 A resolution. A target enzyme for chemotherapy. AB - The atomic structure of glycinamide ribonucleotide transformylase, an essential enzyme in purine biosynthesis, has been determined at 3.0 A resolution. The last three C-terminal residues and a sequence stretch of 18 residues (residues 113 to 130) are not visible in the electron density map. The enzyme forms a dimer in the crystal structure. Each monomer is divided into two domains, which are connected by a central mainly parallel seven-stranded beta-sheet. The N-terminal domain contains a Rossmann type mononucleotide fold with a phosphate ion bound to the C terminal end of the first beta-strand. A long narrow cleft stretches from the phosphate to a conserved aspartic acid, Asp144, which has been suggested as an active-site residue. The cleft is lined by a cluster of residues, which are conserved between bacterial, yeast, avian and human enzymes, and likely represents the binding pocket and active site of the enzyme. GAR Tfase binds a reduced folate cofactor and glycinamide ribonucleotide for the catalysis of one of the initial steps in purine biosynthesis. Folate analogs and multi-substrate inhibitors of the enzyme have antineoplastic effects and the structure determination of the unliganded enzyme and enzyme-inhibitor complexes will aid the development of anti-cancer drugs. PMID- 1522593 TI - The Escherichia coli rpoB60 mutation blocks antitermination by coliphage HK022 Q function. AB - The lambdoid bacteriophage regulate gene expression by suppressing transcription terminators. Although similar in sequence to lambda, HK022 lacks an analogue to the lambda N antitermination gene and a distinct nutR sequence. To define the HK022 antitermination system, we plated the phage on Escherichia coli nus mutants that inhibit lambda N function. Only rpoB60 (also called nusC60) blocked HK022 lytic growth. Analyses of HK022-lambda hybrid phage suggested that a HK022 function analogous to lambda Q was inhibited by rpoB60. This result was confirmed with pR'-tR'-galK fusions. HK022 Q-protein suppressed tR' in wild-type but not in rpoB60 mutants. The lambda Q-protein, although inhibited by rpoB60, was more active than the HK022 analogue. A single amino acid difference between the two Q proteins accounts for the phenotype. Changing the penultimate residue of HK022 Q from alanine to the lambda threonine generated a phage that could propagate on rpoB60 hosts. Host and phage mutations that permitted HK022 growth in rpoB60 strains were characterized. The bacterial suppressors were located in the Escherichia coli nusB gene. The phage suppressors represented recessive mutations in a HK022 b-region sequence encoding an open reading frame of 73 codons. PMID- 1522594 TI - Molecular basis of co-operativity in protein folding. III. Structural identification of cooperative folding units and folding intermediates. AB - The hierarchical partition function formalism for protein folding developed earlier has been extended through the use of three-dimensional polar and apolar contact plots. For each amino acid residue in the protein, these plots indicate the apolar and polar surfaces that are buried from the solvent, the identity of all amino acid residues that contribute to this shielding, and the magnitude of their contributions. These contact plots are then used to examine the distribution of the free energy of stabilization throughout the protein molecule. Analysis of these data allows identification of co-operative folding units and their hierarchical levels, and the identification of partially folded intermediates with a significant probability of being populated. The overall folding/unfolding thermodynamics of 12 globular proteins, for which crystallographic and experimental thermodynamics are available, is predicted within error. An energetic classification of partially folded intermediates is presented and the results compared to those cases for which structural and thermodynamic experimental information is available. Four different types of partially folded states and their structural energies are considered. (1) Local intermediates, in which only a local region of the protein loses secondary and tertiary interactions, while the rest of the protein remains intact. (2) Global intermediates, corresponding to the standard molten globule definition, in which significant secondary structure is maintained but native-like tertiary structure contacts are disrupted. (3) Extended intermediates characterized by the existence of secondary structure elements (e.g. alpha-helices) exposed to solvent. (4) Folding intermediates in proteins with two structural domains. The structure and energetics of folding intermediates of apo-myoglobin, alpha-lactalbumin, phosphoglycerate kinase and arabinose-binding protein are considered in detail. PMID- 1522595 TI - Site-directed mutagenesis of the GTP-binding domain of beta-tubulin. AB - Tubulin binds guanine nucleotides with high affinity and specificity. GTP, an allosteric effector of microtubule assembly, requires Mg2+ for its interaction with beta-tubulin and binds as the MgGTP complex. In contrast, GDP binding does not require Mg2+. The structural basis for this difference is not understood but may be of fundamental importance for microtubule assembly. We investigated the interaction of beta-tubulin with guanine nucleotides using site-directed mutagenesis. Acidic amino acid residues have been shown to interact with nucleotide in numerous nucleotide-binding proteins. In this study, we mutated seven highly conserved aspartic acid residues and one highly conserved glutamic acid residue in the putative GTP-binding domain of beta-tubulin (N-terminal 300 amino acids) to asparagine and glutamine, respectively. The mutants were synthesized in vitro using rabbit reticulocyte lysates, and their affinities for nucleotide determined by an h.p.l.c.-based assay. Our results indicate that the mutations can be placed in six separate categories on the basis of their effects on nucleotide binding. These categories range from having no effect on nucleotide binding to a mutation that apparently abolishes nucleotide binding. One mutation at Asp224 reduced the affinity of beta-tubulin for GTP in the presence but not in the absence of Mg2+. The specific effect of this mutation on nucleotide binding is consistent with an interaction of this amino acid with the Mg2+ moiety of MgGTP. This residue is in a region sharing sequence homology with the putative Mg2+ site in myosin and other ATP-binding proteins. As a result, tubulin belongs to a distinct class of GTP-binding proteins which may be evolutionarily related to the ATP-binding proteins. PMID- 1522596 TI - Active site of trypanothione reductase. A target for rational drug design. AB - The X-ray crystal structure of the enzyme trypanothione reductase, isolated from the trypanosomatid organism Crithidia fasciculata, has been solved by molecular replacement. The search model was the crystal structure of human glutathione reductase that shares approximately 40% sequence identity. The trypanosomal enzyme crystallizes in the tetragonal space group P4(1) with unit cell lengths of a = 128.9 A and c = 92.3 A. The asymmetric unit consists of a homodimer of approximate molecular mass 108 kDa. We present the structural detail of the active site as derived from the crystallographic model obtained at an intermediate stage of the analysis using diffraction data to 2.8 A resolution with an R-factor of 23.2%. This model has root-mean-square deviations from ideal geometry of 0.026 A for bond lengths and 4.7 degrees for bond angles. The trypanosomid enzyme assumes a similar biological function to glutathione reductase and, although similar in topology to human glutathione reductase, has an enlarged active site and a number of amino acid differences, steric and electrostatic, which allows it to process only the unique substrate trypanothione and not glutathione. This protein represents a prime target for chemotherapy of several debilitating tropical diseases caused by protozoan parasites belonging to the genera Trypanosoma and Leishmania. The structural differences between the parasite and host enzymes and their substrates thus provides a rational basis for the design of new drugs active against trypanosomes. In addition, our model explains the results of site-directed mutagenesis experiments, carried out on recombinant trypanothione reductase and glutathione reductases, designed by consideration of the crystal structure of human glutathione reductase. PMID- 1522597 TI - Structural data suggest that the active and inactive forms of the RecA filament are not simply interconvertible. AB - We have used electron microscopy to examine the two major conformational states of the helical filament formed by the RecA protein of Escherichia coli. The compressed filament, formed in the absence of a nucleotide cofactor either as a self-polymer or on a single-stranded DNA molecule, is characterized in solution by about 6.1 subunits per turn of a 76 A pitch helix, and appears to be inactive with respect to all RecA activity. The active state of the filament, formed with ATP or an ATP analog on either a single or double-stranded DNA substrate, has about 6.2 subunits per turn of a 94 A pitch helix. Measurements of the contour length of RecA-covered single-stranded DNA circles in ice, formed in the absence of nucleotide cofactor, indicate that each RecA subunit binds five bases, in contrast to the three bases or base-pairs per subunit in the active state. The different stoichiometries of DNA binding suggests that the two polymeric forms are not interconvertible, as has been suggested on biochemical grounds. A three dimensional reconstruction of the inactive state shows the same general features as the 83 A pitch filament present in the RecA crystal. This structural similarity and the fact that the crystal does not contain ATP or DNA suggests that the crystal structure is more similar to the compressed filament than the active, extended filament. PMID- 1522599 TI - Crystallization of a type I 3-dehydroquinase from Salmonella typhi. AB - Crystals have been grown of a type I 3-dehydroquinase from both Escherichia coli and Salmonella typhi. However, only those from S. typhi diffract to a resolution of 2.3 A on a conventional X-ray source and are suitable for structure determination. The space group has been determined as P2(1)2(1)2 with unit cell dimensions a = 48.01 A, b = 114.29 A, c = 42.87 A. There is one subunit in the asymmetric unit. PMID- 1522598 TI - Crystallization and crystallographic characterization of the iron-sulfur containing DNA-repair enzyme endonuclease III from Escherichia coli. AB - Endonuclease III from Escherichia coli is an iron-sulfur enzyme possessing both DNA N-glycosylase and apurinic/apyrimidinic lyase activities. It could serve to repair damaged thymine residues in DNA via base excision-repair. We have crystallized endonuclease III by a combination of dialysis and seeding techniques after exploration of a wide variety of precipitants which failed to yield macroscopic crystals. Important features of the optimized crystallization include: the use of 5 to 10% glycerol, a temperature of 15 degrees C, controlled dialysis to decrease ionic strength and macroseeding using a 200 mM-NaCl transfer buffer to dissolve microcrystalline contamination. The crystals belong to space group P2(1)2(1)2(1) with unit cell dimensions of a = 48.5 A, b = 65.8 A, c = 86.8 A, alpha = beta = gamma = 90 degrees, have one 23 kDa monomer per asymmetric unit, and diffract to 1.84 A. A native anomalous Patterson map located the iron sulfur cluster and reaffirmed its existence. The reported crystallization procedures ensure an ample supply of crystals for the extensive heavy-atom derivative search necessary for this labile iron-sulfur enzyme. The elucidation of endonuclease III structure will facilitate not only the understanding of glycosylase and lyase mechanisms but also the structure and function of this new class of iron-sulfur proteins. PMID- 1522600 TI - Preliminary X-ray crystallographic studies on alcohol dehydrogenase from Drosophila. AB - The alcohol dehydrogenase (ADHase) enzyme catalyses the oxidation of alcohols to aldehydes or ketones using NAD+ as a cofactor. Functional ADHase from Drosophila lebanonensis is a dimer, with a monomeric molecular weight of 27,000 and with 254 residues in each polypeptide chain. Crystals of the protein have been grown with and without NAD+. Two crystal forms have been observed. Most crystals are plate like, 0.05 mm in their shortest dimension and up to 0.4 mm in their longest dimension. These crystals are generally too small to diffract efficiently using conventional X-ray sources, so preliminary studies were carried out using the Synchrotron Radiation Source at the SERC Daresbury Laboratory. Twinning was a severe problem with this crystal form. The second form is grown in the absence of NAD+ but with DL-dithiothreitol present. These crystals grow more evenly and diffract to better than 2 A resolution. They are monoclinic, with cell dimensions, a = 81.24(6) A, b = 55.75(4) A, c = 109.60(7) A and beta = 94.26(9) degrees, space group P2(1). There are two dimers in the asymmetric unit, but at low resolution a rotated cell with one dimer per asymmetric unit can be obtained. PMID- 1522601 TI - Characterization of DNA-binding and strand-exchange stimulation properties of y RPA, a yeast single-strand-DNA-binding protein. AB - Single-stranded DNA binding proteins (SSBs) have been isolated from many organisms, including Escherichia coli, Saccharomyces cerevisiae and humans. Characterization of these proteins suggests they are required for DNA replication and are active in homologous recombination. As an initial step towards understanding the role of the eukaryotic SSBs in DNA replication and recombination, we examined the DNA binding and strand exchange stimulation properties of the S. cerevisiae single-strand binding protein y-RPA (yeast replication protein A). y-RPA was found to bind to single-stranded DNA (ssDNA) as a 115,000 M(r) heterotrimer containing 70,000, 36,000 and 14,000 M(r) subunits. It saturated ssDNA at a stoichiometry of one heterotrimer per 90 to 100 nucleotides and binding occurred with high affinity (K omega greater than 10(9) M 1) and co-operativity (omega = 10,000 to 100,000). Electron microscopic analysis revealed that y-RPA binding was highly co-operative and that the ssDNA present in y-RPA-ssDNA complexes was compacted fourfold, arranged into nucleosome-like structures, and was free of secondary structure. y-RPA was also tested for its ability to stimulate the yeast Sepl and E. coli RecA strand-exchange proteins. In an assay that measures the pairing of circular ssDNA with homologous linear duplex DNA, y-RPA stimulated the strand-exchange activity of Sepl approximately threefold and the activity of RecA protein to the same extent as did E. coli SSB. Maximal stimulation of Sepl occurred at a stoichiometry of one y-RPA heterotrimer per 95 nucleotides of ssDNA. y-RPA stimulated RecA and Sepl mediated strand exchange reactions in a manner similar to that observed for the stimulation of RecA by E. coli SSB; in both of these reactions, y-RPA inhibited the aggregation of ssDNA and promoted the co-aggregation of single-stranded and double-stranded linear DNA. These results demonstrate that the E. coli and yeast SSBs display similar DNA-binding properties and support a model in which y-RPA functions as an E. coli SSB-like protein in yeast. PMID- 1522602 TI - Effect of terminal non-homology on intramolecular recombination of linear plasmid substrates in Escherichia coli. AB - Circular dimer plasmids linearized with a restriction endonuclease undergo intramolecular recombination to yield recombinant circular monomers at high efficiency by a recA-independent mechanism in Escherichia coli recB recC sbcA mutants. The rate of this reaction is at least 1000-fold higher than the recombination rate observed for circular plasmid recombination substrates in the same mutants. Three potential models have been previously proposed to explain the recombination events observed. The validity of these models was tested in recA recB recC sbcA mutants using additional recombination substrates. These substrates, when linearized by incubation with an appropriate restriction enzyme, contain non-homologous adenovirus 2 DNA on one or both ends. The data indicate that terminal non-homology does not significantly affect the efficiency of recovering recombinants. In contrast to many recombination models proposed that involve the invasion of homologous duplex DNA by single-stranded DNA ends, the intramolecular recombination reaction studied here does not appear to involve direct pairing from the end(s) of the substrate DNA. Furthermore, the results are consistent with a model proposing that pairing and strand exchange occur between two homologous duplex regions within the linear dimer molecule. PMID- 1522603 TI - Alpha-tubulin gene family of maize (Zea mays L.). Evidence for two ancient alpha tubulin genes in plants. AB - Among 81 alpha-tubulin cDNA clones prepared from RNA from maize seedling shoot, endosperm and pollen, we identified six different alpha-tubulin coding sequences. The DNA sequence analysis of coding and non-coding regions from the clones showed that they can be classified into three different alpha-tubulin gene subfamilies. Genes within each subfamily encode proteins that are 99 to 100% identical in amino acid sequence. Deduced amino acid sequence identity between genes in different subfamilies ranges from 89 to 93%. The results of hybridizations of genomic DNAs to alpha-tubulin coding region probes and to 3' non-coding region probes constructed from six different alpha-tubulin cDNA clones indicated that the maize alpha-tubulin gene family contains at least eight members. Comparison of deduced alpha-tubulin amino acid sequences from maize and the dicot species Arabidopsis thaliana showed that alpha-tubulin isotypes encoded by genes in maize subfamilies I and II are more similar to specific Arabidopsis gene products (96 to 97% amino acid identity) than to isotypes encoded by genes in the other maize subfamilies. Phylogenetic analyses revealed that genes in these two subfamilies were derived from two ancient alpha-tubulin genes that predate the divergence of monocots and dicots. These same analyses revealed that the gene in maize subfamily III is more closely related to sequences from subfamily I genes than to those from subfamily II genes. However, the subfamily III gene has no close counterpart in Arabidopsis. We found evidence of a transposable element-like insertion in the subfamily III gene in some maize lines. PMID- 1522604 TI - 1H nuclear magnetic resonance studies of the interaction of urea with hen lysozyme. Origins of the conformational change induced in hen lysozyme by N acetylglucosamine oligosaccharides. AB - The interaction between hen lysozyme and urea has been investigated using 1H nuclear magnetic resonance spectroscopy. Chemical shift changes for resonances of a number of residues in the vicinity of the active site of the protein have been observed in the presence of urea prior to denaturation. These shifts are similar to those induced in the hen lysozyme spectrum by the specific binding of N acetylglucosamine (GlcNAc) in site C of the active site cleft, indicating that urea and GlcNAc induce a similar conformational change in the enzyme. This implies that the conformational changes experienced by the enzyme on the binding of GlcNAc oligosaccharides are the consequence of interactions, possibly hydrogen bonding, involving the N-acetyl group of the sugar residue bound in site C, rather than the result of contacts between the protein and the pyranose rings of the oligosaccharides. This suggests that hen lysozyme employs an induced fit type mechanism to discriminate for N-acetylated saccharides as substrates. PMID- 1522605 TI - Tubulin gene expression in maize (Zea mays L.). Change in isotype expression along the developmental axis of seedling root. AB - Two-dimensional gel/western blot analysis was used to characterize alpha- and beta-tubulin isotype expression along the developmental axis of the maize (Zea mays) seedling primary root. We identified four distinct alpha-tubulin isotypes and a minimum of six beta-tubulin isotypes. This analysis showed differences between the alpha- and beta-tubulin isotypes expressed in rapidly dividing tissue at the root tip and differentiated root tissues proximal to the tip. The alpha 1 and alpha 4 isotypes predominated in samples from immature rapidly dividing tissues such as root tips, whereas in mature tissues such as differentiated root and pollen, alpha 2, alpha 3 and alpha 4 isotypes predominated. The beta 1 and beta 2 isotypes were more abundant in protein samples from root cortex than in samples from the root tip or vascular cylinder. In contrast, the beta 4 and beta 5 isotypes appeared to be more abundant in root tip and vascular cylinder samples than in root cortex samples. Hybridization probes from the 3' non-coding region of six alpha-tubulin cDNA clones were used to quantify the levels of corresponding tubulin transcripts in selected tissues, from embryonic to mature and from largely undifferentiated to highly differentiated. The results from these hybridization experiments showed that all of the alpha-tubulin genes were expressed in all tissues examined, although each gene showed a unique pattern of differential transcript accumulation. A transcript produced from cDNA clone representing the tua5 alpha-tubulin gene was translated in vitro and produced an alpha-tubulin that comigrated with the alpha 2 isotype. PMID- 1522606 TI - Inhibition of benzo[a]pyrene-induced bone marrow micronuclei formation by diallyl thioethers in mice. AB - Diallyl thioethers (DATEs), naturally occurring compounds present in garlic, were investigated for their putative ability to inhibit benzo[a]pyrene-induced genotoxicity in ICR and C3H strains of mice. The mouse bone marrow micronucleus assay was used as an indicator of in vivo genotoxicity. A dose of 0.67 mmol total DATEs/kg body weight inhibited formation of micronucleated polychromatic erythrocytes (MPCEs) by 24%, and 0.33 mmol DATEs inhibited formation of MPCEs by 45%. Possibly the toxicity of DATEs accounted for less inhibition with the higher dose. Formation of MPCEs were inhibited only slightly by DATEs in C3H mice. These results indicate that the mouse bone marrow micronucleus assay can be used to identify organosulfur components of garlic that inhibit genotoxicity. PMID- 1522607 TI - Dichloroacetic acid and trichloroacetic acid increase chloroform toxicity. AB - Dichloro- and trichloroacetic acids (DCA and TCA) and chloroform are formed during chlorination disinfection of drinking water. The effects of DCA and TCA treatment on CHCl3 toxicity were assessed in these studies. Male and female rats were gavaged with DCA or TCA (0.92 and 2.45 mmol/kg administered 3 times over 24 h). Three hours after the last dose CHCl3 was injected ip (0.75 mg/kg). Male rats experienced some weight loss (15%) and slight increases of ALT and BUN, but there were no effects of either DCA or TCA on any of these responses. In females, CHCl3 increased plasma ALT and this response was greater (up to threefold) in the DCA group, compared to saline controls. Similarly, BUN was increased by CHCl3 and this was more severe (up to threefold) in both the DCA and TCA pretreated groups. These results show that CHCl3 toxicity is increased by DCA and TCA, and this effect is gender-specific, occurring only in females. DCA increases both liver and kidney toxicity, whereas TCA affects only kidney toxicity. PMID- 1522608 TI - Toxicity assessment of atrazine, alachlor, and carbofuran and their respective environmental metabolites using Microtox. AB - Using the Microtox method of toxicity assessment designed by Microbics Corporation, the relative toxicities of alachlor, atrazine, and carbofuran, three pesticides commonly used in agricultural production, were determined. Generally, carbofuran was found to be most acutely toxic, followed closely by atrazine. Alachlor was least toxic of the three pesticides tested. Selected environmental metabolites of these three agri-chemicals were also tested using the same method. Hydroxyalachlor, deethylatrazine, deisopropylatrazine, 3-hydroxycarbofuran, and 3 ketocarbofuran were selected for analysis because previous studies determined their presence in surface and ground-water supplies along with their parents. Results showed that often the metabolites were at least as acutely toxic as their parents, particularly in the case of 3-ketocarbofuran and hydroxyalachlor, which demonstrated toxicities higher or not significantly different than their parents. Hydroxycarbofuran was assessed as the least toxic of all substances tested. The atrazine environmental metabolites were less toxic than their parent. PMID- 1522609 TI - Hepatotoxic interactions of ethanol with allyl alcohol or carbon tetrachloride in rats. AB - To assess whether potential toxic interactions occur between ethanol and allyl alcohol or carbon tetrachloride following subacute, concurrent chemical exposure, male Fischer 344 rats, approximately 70 d of age, were given ethanol at 0, 0.05, 0.1, 0.2, or 0.5 ml/kg in corn oil daily by gavage for 14 d (ETOH group), or the same levels of ethanol with 21 mg allyl alcohol/kg (ALAC group), or the same levels of ethanol with 20 mg carbon tetrachloride/kg (CCL4 group). Hepatic response was assessed 24 h after the last dose. Interactions were evaluated by comparing the ETOH group with either the ALAC group or the CCL4 group using multivariate analysis of variance procedures. No statistically significant interaction was seen between the ETOH group and the ALAC group at the dosages used. Although an interaction between ethanol and carbon tetrachloride given simultaneously was not statistically significant, a small interactive effect on weight gain from d 0 to termination was apparent (p = .057). Exposure to ethanol alone resulted in a concentration-dependent decrease in absolute and relative liver weight, with a threshold between 0.05 and 0.1 ml/kg. There was no histopathological evidence of hepatic damage with ethanol alone, and no effect on hepatic cytochrome P-450 and glutathione levels or on serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), and alkaline phosphatase (ALK). Exposure to allyl alcohol alone resulted in significant increases in absolute and relative liver weights, liver glutathione, and periportal hepatocellular vacuolar degeneration. Exposure to carbon tetrachloride alone resulted in significant increases in absolute and relative liver weight, serum levels of ALT, AST, and ALK, and centrilobular hepatocellular vacuolar degeneration and necrosis. These observations indicate that subacute, concurrent exposure of ethanol with carbon tetrachloride or allyl alcohol at ethanol levels comparable to those reported in gavage vehicles did not result in interactive toxicity. PMID- 1522610 TI - Review of the allergic contact dermatitis hazard posed by chromium-contaminated soil: identifying a "safe" concentration. AB - At least 200 sites in the United States contain soil with elevated levels of trivalent and hexavalent chromium [Cr(III) and Cr(VI)]. Although the potential cancer hazard posed by airborne Cr(VI) has been the primary concern for these sites, a soil cleanup standard based on the potential elicitation of allergic contact dermatitis has been proposed for sites in Hudson County, N.J. This paper describes the rationale for identifying a soil concentration of Cr(VI) that should not pose an allergic contact dermatitis hazard-even in sensitized persons. A literature review of eight published patch test studies that evaluated the allergic response to potassium dichromate was conducted. These studies were evaluated for clinical and statistical relevance in establishing a threshold dose of Cr(VI) to which no more than 10% of the subpopulation sensitized to chromium would respond, and that would protect at least 99.84% of the general population. Although each of the studies had certain methodological limitations when evaluated against current test methods, the data set proved useful for deriving an estimated threshold. Using computer data-fitting techniques based on truncated lognormal distributions, a weighted mean 10% threshold of approximately 150 ppm potassium dichromate or 54 ppm Cr(VI) was identified for the eight studies. Due to the types of limitations noted for these studies, this threshold is likely to be somewhat conservative. Test results have shown that between 5 and 10% of the Cr(VI) at concentrations less than about 500 ppm are released from a soil matrix into an isotonic saline solution simulating sweat. Using human sweat as the extractant, it has been shown that only 0.1% of the CR(VI) at concentrations of approximately 1,000 ppm are released from a soil matrix into sweat. Based on 10% solubilization of soil-bound Cr(VI) and the results of our statistical analysis of previous threshold studies, a concentration of approximately 350 to 500 ppm Cr(VI) in soil should be sufficiently low to protect virtually all exposed people, including children, from chromium-induced allergic contact dermatitis. PMID- 1522611 TI - Role of oxidative stress in single-dose, cadmium-induced testicular cancer. AB - Treatment of rats with a single carcinogenic dose of CdCl2 (i.e., 30 mumol/kg) caused severe hemorrhagic damage in the testis within the first 12 h after the metal. Subsequently, atrophy with calcification developed in the next 2-3 mo. Atrophied tissues regenerated during the 1 yr after exposure. Twelve hours after exposure to the Cd treatment, lipid peroxidation levels, Fe content, and cellular production of H2O2 were remarkably elevated in testicular Leydig cells, the target cell population for Cd carcinogenesis. At the same time, glutathione peroxidase activity rose, glutathione reductase and catalase activities were reduced, and superoxide dismutase activity was unchanged. Xanthine oxidase activity in Leydig cells was also elevated at 6 and 9 h after the Cd treatment. Reduced glutathione in testes was decreased and oxidized glutathione was increased 12 h after exposure to the metal. These facts suggest that the carcinogenic doses of Cd induced oxidative stress while compromising cellular defense mechanisms against such stress. Therefore, active oxygen species such as H2O2 may have an important role in the initiation of carcinogenesis within the target cell population. PMID- 1522612 TI - Urethanase in rat tissues. AB - Urethane-hydrolyzing activity (urethanase) was found in the homogenates of liver, kidney, and lung of rats. The activity was significantly higher at acidic condition (pH 5.0) than that at neutral condition (pH 7.0) in every case. The highest activity among them was observed in a kidney homogenate preparation. The activities increased slightly with treatment by Triton X-100. Intracellular distribution of urethanase in rat kidney was examined and found that the enzyme activity located mainly in the lysosomal fraction. The optimal pH was found to be 5.0. The enzyme activity was strongly inhibited by EDTA, whose 50% inhibitory concentration was 7.4 x 10(-7) M. Complete loss of the enzyme activity by the addition of EDTA was fully recovered by the addition of Zn2+, which suggested that urethanase belongs to the category of Zn enzyme. PMID- 1522613 TI - Embryotoxic and teratogenic effects of intraperitoneally administered metavanadate in mice. AB - Metavanadate was evaluated for developmental toxicity in pregnant Swiss mice. Sodium metavanadate (NaVO3) was administered intraperitoneally on d 6-15 of gestation at doses of 0, 2, 4, or 8 mg/kg/d. On gestation d 18, all live fetuses were examined for external, visceral, and skeletal malformations and variations. Maternal toxicity was observed at 2, 4, and 8 mg/kg/d as evidenced by decreased weight gain during treatment. Increased resorptions and dead fetuses, increased percentage postimplantation loss, and reduced fetal body weight per litter were observed at 4 and 8 mg/kg/d. There were no significant increases in the type or incidence of external and skeletal anomalies, but a significant increase in the incidence of cleft palate was detected at 8 mg/kg/d. The lowest-observed-adverse effect level (LOAEL) for maternal toxicity was 2 mg NaVO3/kg/d, while 2 mg/kg/d was also the no-observed-adverse-effect level (NOAEL) for significant developmental toxicity. PMID- 1522614 TI - Dermal absorption of chemicals: effect of application of chemicals as a solid, aqueous paste, suspension, or in volatile vehicle. AB - The purpose of this study was to investigate the dermal absorption of chemicals in different physical forms when applied to female F344 rats. Chemicals were applied either as a solid, aqueous paste, suspension, or dissolved in the volatile vehicle ethanol. The chemicals investigated were [14C]-2-sec-butyl-4,6 dinitrophenol (DNBP, 4.2 mumol), 2,4,5,2',4',5'-[14C]-hexachlorobiphenyl (HCB, 2.3 mumol), and 3,4,3',4'-[14C]-tetrachlorobiphenyl (TCB, 0.5 mumol). The chemicals were applied on the clipped mid-dorsal region of the rat over a 2.54 cm2 treatment area, which was then occluded. Urine and feces were collected and assayed for radioactivity. Twenty-four hours post-application, the treated skin was washed with a mixture (1:1) of soap and water, dried, and reoccluded. The animals were sacrificed at 120 h by exsanguination under ether anesthesia. Radioactivity in the blood, skin (treated and untreated), and carcass was assayed. Dermal absorption of DNBP-derived radioactivity was approximately 50% of the recovered dose after application in the four physical forms, and the major route of excretion was via the urine. Twelve percent of the absorbed dose of DNBP was retained in the body. Dermal penetration of HCB-derived radioactivity was 5 8% of the recovered dose after application in the four forms, and the major route of excretion was via the feces. Greater than 90% of the absorbed dose of HCB derived radioactivity was retained in the body. Dermal penetration of TCB-derived radioactivity was 6-8% of the recovered dose in the four forms, and the major route of excretion was via the feces. Approximately 21% of the absorbed dose was retained in the body at 120 h. Absorption of each chemical applied either as solid, aqueous paste, or suspension was compared to the absorption of the same chemical in ethanol. Absorption of HCB applied as a solid was significantly higher (p less than or equal to .05) as compared to HCB applied in ethanol. There were no other significantly differences in the comparisons of absorption. The data indicate that the chemicals examined in this study can penetrate the skin as readily when applied either as a solid, aqueous paste, or suspension, as when applied in the volatile vehicle ethanol. PMID- 1522615 TI - PCDD and PCDF in human milk from Scandinavia, with special emphasis on Norway. AB - Levels of polychlorinated dibenzo-p-dioxins (PCDD) and polychlorinated dibenzofurans (PCDF) were measured in human milk in a collaborative Scandinavian study with 10 samples from each of 7 locations in Norway and Sweden (total 70 samples) and 10 samples from Denmark. Four locations represented areas with different PCDD and PCDF sources and three background areas. Norwegian results are presented and related to the Danish and Swedish values. No geographical differences were found in total dioxins expressed as Nordic TCDD equivalents. Mean equivalent values (pg/g fat basis) were 15-18 in Norway and Denmark and 20 24 in Sweden, lower than those reported from parts of Western Europe but higher than in the undeveloped countries. When looking at the individual compounds, the highest values of PCDD congeners were observed in industrialized areas of Sweden, while the highest PCDF values were found in a Norwegian area known for dioxin contamination from a magnesium-producing factory. PMID- 1522616 TI - Toxicokinetics of mercuric chloride and methylmercuric chloride in mice. AB - Future human exposure to inorganic mercury will probably lead to a few individuals occupationally exposed to high levels and much larger populations exposed to low or very low levels from dental fillings or from food items containing inorganic mercury; human exposure to methylmercury will be relatively low and depending on intake of marine food. Ideally, risk assessment is based on detailed knowledge of relations between external and internal dose, organ levels, and their relation to toxic symptoms. However, human data on these toxicokinetic parameters originate mainly from individuals or smaller populations accidentally exposed for shorter periods to relatively high mercury levels, but with unknown total body burden. Thus, assessment of risk associated with exposure to low levels of mercury will largely depend on data from animal experiments. Previous investigations of the toxicokinetics of mercuric compounds almost exclusively employed parenteral administration of relatively high doses of soluble mercuric salts. However, human exposure is primarily pulmonary or oral and at low doses. The present study validates an experimental model for investigating the toxicokinetics of orally administered mercuric chloride and methylmercuric chloride in mice. Major findings using this model are discussed in relation to previous knowledge. The toxicokinetics of inorganic mercury in mice depend on dose size, administration route, and sex, whereas the mouse strain used is less important. The "true absorption" of a single oral dose of HgCl2 was calculated to be about 20% at two different dose levels. Earlier studies that did not take into account the possible excretion of absorbed mercury and intestinal reabsorption during the experimental period report 7-10% intestinal uptake. The higher excretion rates observed after oral than after intraperitoneal administration of HgCl2 are most likely due to differences in disposition of systemically delivered and retained mercury. After methylmercury administration, mercury excretion followed first-order kinetics for 2 wk, independently of administration route, strain, or sex. However, during longer experimental periods, the increasing relative carcass retention (slower rate of excretion) caused the elimination to deviate from first-order kinetics. Extensive differences in the toxicokinetics of methylmercury with respect to excretion rates, organ deposition, and blood levels were observed between males and females.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1522618 TI - The effect of altitude on the umbilical artery Doppler resistance. AB - This study examined whether there were differences between the umbilical artery systolic-diastolic (S/D) ratio and resistance index (RI) in patients with normal fetuses living at sea level (group I) and those living between 4,200 and 4,500 feet above sea level (group II). Linear regression demonstrated a significant association (P less than 0.001) between gestational age and the S/D ratio and RI for groups I (n = 100) and II (n = 128). Least-squares regression analysis demonstrated no significant differences in slopes or intercepts between groups I and II. The results would suggest that altitude, up to 4,500 feet above sea level, does not affect umbilical artery Doppler resistance in normal fetuses. PMID- 1522617 TI - Assessment of the empty follicle syndrome by transvaginal sonography. AB - The empty follicle syndrome was assessed using transvaginal ultrasonography in a group of 152 consecutive women with unmedicated menstrual cycles being studied because of primary or secondary infertility or repetitive miscarriage. The overall frequency of the empty follicle syndrome was found to be 43.4%. The frequency increased with age but was independent of gravidity. The empty follicle syndrome may be a significant etiologic factor in infertility or other reproductive abnormalities, and transvaginal ultrasound represents a good, non invasive means of evaluating it. PMID- 1522619 TI - First trimester findings in pregnancies after in vitro fertilization. AB - We assessed the frequency of abnormal sonographic findings and their significance with respect to outcome in pregnancies resulting from in vitro fertilization (IVF). We retrospectively reviewed first trimester sonograms of 53 consecutive IVF patients who had a positive pregnancy test and first trimester ultrasonography at least 4 weeks after embryo transfer, and we correlated the sonographic findings with pregnancy outcome. For controls, we compared the frequency of sonographic abnormalities in these study patients to that in a group of patients who became pregnant after ovulation induction only. In the 53 IVF patients, the numbers of gestational sacs identified on the initial sonogram were as follows: 34 singletons, 11 twins, two triplets, one quadruplets and one quintuplets; no sac was seen in four patients. In 32 patients, the first sonogram was normal, with a visualized yolk sac, or heartbeat, or both. In 10 patients the gestational sac appeared abnormal but sac contents were normal. In seven patients an abnormality of sac contents was identified, including four with an embryo but no heartbeat and three anembryonic sacs. Overall, 40% of IVF patients had sonographic abnormalities, in comparison to 7% in the control group of patients (P less than 0.05, Fisher's exact test). Of the 32 patients with normal sonograms, 26 (81%) delivered at least one live infant. Of the 10 patients whose gestation sacs appeared abnormal, nine (90%) gave birth to live infants. Of the seven patients with abnormal sac contents, two (29%) delivered at least one live infant. We conclude that abnormal findings are frequently present on the initial sonogram of pregnant patients after IVF.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1522620 TI - Placenta accreta: additional sonographic observations. PMID- 1522621 TI - A comparison of duplex Doppler sonography of the ligamentum teres and portal vein with endoscopic demonstration of gastroesophageal varices in patients with chronic liver disease or portal hypertension, or both. AB - The ability of duplex Doppler sonography of the ligamentum teres and portal vein to detect specific signs of portal hypertension was compared with the ability of endoscopy to demonstrate gastroesophageal varices in consecutive patients. Among 90 patients with parenchymal liver disease and a high probability of portal hypertension, 70 had varices, 72 had specific sonographic signs, and four had neither. Ultrasonography was comparable to endoscopy irrespective of the clinical severity of the underlying liver disease. Eleven patients had vascular occlusive diseases; nine had varices; and all had at least one sonographic sign. Duplex Doppler ultrasonography may have a clinical role in noninvasive detection of portal hypertension. Further studies correlating the findings with those of portal pressure are needed to define the place of duplex Doppler ultrasonography as a predictor of the presence of portal hypertension. PMID- 1522622 TI - Evaluation of adnexal masses with transvaginal color ultrasonography. PMID- 1522623 TI - Placenta accreta: prospective sonographic diagnosis in patients with placenta previa and prior cesarean section. AB - A prospective evaluation for possible placenta accreta was performed in 34 patients with placenta previa and a history of one or more cesarean sections. Sonographic criteria used included (1) loss of the normal hypoechoic retroplacental myometrial zone, (2) thinning or disruption of the hyperechoic uterine serosa-bladder interface, and (3) presence of focal exophytic masses. Of 18 patients with positive sonographic results, 14 had proof of placenta accreta and 16 of the patients underwent hysterectomy. Of 16 patients with negative sonographic results, only one had placenta accreta, and two patients required hysterectomy. Presence of numerous intraplacental vascular lacunae appears to be an additional risk criterion for placenta accreta, separate from the other criteria listed above. PMID- 1522624 TI - The aortic and pulmonary outflow tract screening examination in the human fetus. AB - Imaging of the aortic and pulmonic outflow tracts in the fetus may be difficult owing to fetal position. This study describes two screening methods for imaging the outflow tracts, depending on whether the interventricular septum was tangential (group I) or perpendicular (group II) to the ultrasonic beam. We performed 170 examinations during the second and third trimesters of pregnancy. The outflow tracts were imaged in 166 (97.6%). Fetuses in group I were identified much less frequently (13.2%) than fetuses in group II (86.8%). This study would suggest that for the outflow tracts to be imaged during a screening examination, the sonographer should become familiar with the sonographic anatomy of the outflow tracts when the interventricular septum is perpendicular to the ultrasound beam. PMID- 1522625 TI - Tubular ectasia within the mediastinum testis. AB - Eleven scrotal sonographic examinations showing a spectrum of findings within the mediastinum testis were collected over a 2 year period. Each case showed numerous small tubular or rounded anechoic structures within the mediastinum testis; often, the findings mimicked a hypoechoic mass. Findings were bilateral in eight of ten patients; one additional patient had only one testis because of orchiectomy. All patients had an associated extratesticular finding, in most cases a spermatocele. Tubular ectasia shares several features with testicular cysts and mechanisms of formation are postulated to be similar to those previously proposed for testicular cysts. Recognizing tubular ectasia is important to avoid unnecessary concern and potential surgery. PMID- 1522626 TI - Pseudoulceration of the carotid artery. PMID- 1522627 TI - New potential for endovascular ultrasonography. PMID- 1522628 TI - Septated hypoechoic perirenal fat on sonograms: a pitfall in renal ultrasonography. PMID- 1522629 TI - Cervical ectopic pregnancy: avoiding pitfalls in the ultrasonographic diagnosis. PMID- 1522630 TI - Prenatal diagnosis of adrenal hemorrhage by ultrasonography. PMID- 1522631 TI - Sonographic demonstration of annular pancreas in the newborn. PMID- 1522632 TI - Bertram M. Bernheim: a southern vascular surgeon. PMID- 1522633 TI - Contemporary surgical management of renovascular disease. AB - To examine the treatment methods and early results of renovascular repair in our contemporary patient population, we reviewed our surgical experience during a recent 54-month period. From January 1987 to July 1991, 200 patients ranging in age from 5 to 80 years (mean, 56 years) were operated on for correction of nonatherosclerotic (43 patients) and atherosclerotic (157 patients) renovascular disease. The group included 92 men and 108 women, with blood pressures ranging from 300/198 mm Hg to 120/70 mm Hg (mean, 205/113 mm Hg). Defined by preoperative serum creatinine, 129 patients (65%) had evidence of renal insufficiency (Cr greater than or equal to 1.3 mg/dl), whereas 71 patients (36%) had severe renal insufficiency (Cr greater than 2.0 mg/dl; 11 patients were dependent on dialysis). One hundred forty-seven patients with atherosclerotic renovascular disease (94%) demonstrated organ-specific atherosclerotic damage. Operative management of 291 kidneys included unilateral renal artery repair in 117 patients (58%), bilateral repair in 78 patients (39%), and primary nephrectomy in five patients (2.5%). Simultaneous aortic reconstruction was required in 64 patients (32%). There were five operative deaths (2.5% mortality rate) and four occluded renovascular repairs (1.4% primary failure) within 30 days of surgery. Hypertension was considered cured in 21% and improved in 70% of 195 operative survivors. In 70 patients with severe renal insufficiency before operation, estimated glomerular filtration rate was improved in 49% (8 of 11 patients removed from dialysis), unchanged in 36%, and worsened in 15%. Renal function response was significantly influenced by the site of disease and the operation. Twenty-six additional postoperative deaths occurred during follow-up (range, 6 to 58 months; mean, 24.4 months). Extreme atherosclerotic-renovascular disease, preoperative renal insufficiency, failure to improve renal function, and progression to dependence on dialysis after operation were associated with follow up deaths. Although most patients had a beneficial outcome, failure to improve extreme renal insufficiency was associated with a rapid rate of death during a relatively short follow-up period. PMID- 1522634 TI - Penetrating abdominal aortic trauma: a report of 129 cases. AB - The clinical presentation, resuscitation, and operative management of 129 patients with penetrating injuries to the abdominal aorta treated between 1960 and 1989 were reviewed. This is the largest reported civilian or military experience with this specific injury; our review of the literature was limited to reports focusing on the detailed analysis of the management and outcome of aortic trauma. Eighty-two percent of patients were in shock; 18 patients (14%) underwent emergency room thoracotomies, with no survivors. Of 46 patients requiring operating room thoracotomies, only 20% survived. All patients underwent exploration. Thirty percent had three or more visceral injuries; only 2% had no concurrent visceral injury. There were associated vascular injuries in 58% of patients, the inferior vena cava being the most frequent (37%). The most significant predictor of death was continued bleeding at operation. Ninety percent of patients with free intraperitoneal bleeding died, in contrast to 35% with a contained retroperitoneal hematoma (p less than 0.001). Aortic injuries were supraceliac in 25% of patients, between the celiac and renal arteries in 25%, and infrarenal in 50%. The respective mortality rates were 70%, 80%, and 47% (p less than 0.05). Repair of the aortic defect was possible in 103 patients (80%). The most common repair was lateral arteriorrhaphy in 53% of patients, followed by end-to-end anastomosis in 15% and prosthetic repairs in 8%. The overall mortality rate was 62%, which is similar to that of previous reports. Despite advances in trauma care, a functioning paramedic system, and the use of aggressive means to obtain aortic control, penetrating aortic trauma remains highly lethal. PMID- 1522635 TI - Are gram-negative bacteria a contraindication to selective preservation of infected prosthetic arterial grafts? AB - Management of infected prosthetic arterial grafts has traditionally included total graft excision especially when gram-negative bacteria were cultured. Between 1973 and 1991 we treated 42 patients with infected prosthetic grafts (33 polytetrafluoroethylene (PTFE), 9 Dacron) by complete graft preservation when the graft was patent, the anastomoses were intact, and the patient did not have sepsis. The infection involved the anastomosis (36 cases) or the body (6 cases) of 33 peripheral grafts and the distal segment of five aortofemoral and four iliac-distal grafts. Cultures of the 42 infected grafts grew gram-positive bacteria in 33 cases and gram-negative bacteria in 22 cases. Treatment adjuncts included repeated, radical operative wound debridement and rarely (7 of 42) rotational muscle flaps. This management resulted in a 10% (4 of 42) hospital mortality rate and an amputation rate in survivors of 3% (1 of 38 threatened limbs). All four deaths were due to sepsis: gram-positive bacteria were cultured in all cases and gram-negative bacteria in two cases. Of the 38 survivors, 29 (76%) wounds healed and remained healed after average follow-up of 3 years (range, 1 to 18 years). Nine other patients required total graft excision for nonhealing wounds (7 cases) or delayed anastomotic hemorrhage (2 cases). Gram negative bacteria were cultured in four, and gram-positive bacteria were cultured in six of these nine wounds. Four of nine (44%) graft infections that cultured Pseudomonas organisms healed without complications versus 23 of 33 (70%) wounds that cultured gram-positive bacteria, and 12 of 13 (92%) wounds that cultured gram-negative bacteria other than Pseudomonas organisms.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1522636 TI - Does contralateral internal carotid artery occlusion increase the risk of carotid endarterectomy? AB - The results of every carotid endarterectomy performed contralateral to an internal carotid artery occlusion (n = 36) (group I) were compared with those performed contralateral to a patent internal carotid artery (n = 169) (group II) over the last 10 years. The patients in each group were evenly matched with respect to male gender (66% vs 69%); mean age (66.7 vs 65.9 years); and incidence of hypertension (55.6% vs 53.2%), diabetes (16.7% vs 20.1%), and hyperlipidemia (8.3% vs 11.8%). Patients in group I had a higher incidence of previous myocardial infarction (25% vs 11.8%, p less than 0.05) and exertional angina (55.6% vs 29.6%, p less than 0.01). Indications for carotid endarterectomy were equivalent, including stroke (19.4% vs 21.9%), transient ischemic attacks (36.1% vs 35.5%), amaurosis fugax (16.7% vs 11.8%), nonhemispheric symptoms (5.6% vs 8.3%), and asymptomatic stenoses (22.2% vs 22.5%), respectively. Perioperative strokes occurred in one (2.8%) patient in group I and seven (4.1%) patients in group II (NS). Among the patients in group II the incidence of perioperative stroke did not correlate directly with the degree of contralateral ICA stenosis: greater than 90% (4%); 70% to 90% (6.7%); 50% to 70% (8.7%); and less than 50% (2.8%). The operative mortality rate was 0% among patients in group I and 1.2% among patients in group II (NS). Cardiac complications occurred in two (5.6%) patients in group I and nine (5.3%) patients in group II (NS).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1522637 TI - The evolving surgical management of recurrent carotid stenosis. AB - The traditional approach to recurrent carotid stenosis has been repeat endarterectomy or patch angioplasty. Concern with the durability of repeat carotid endarterectomy has resulted in our use of carotid resection with autogenous graft interposition. This study was designed to determine the outcome and efficacy of carotid resection compared with repeat carotid endarterectomy in the management of recurrent carotid stenosis. From 1974 to 1991, 162 operations (repeat carotid endarterectomy 105, carotid resection 57) were performed for recurrent carotid stenosis. Indication for operation was hemispheric symptoms in 63% of patients, nonlateralizing symptoms in 25%, asymptomatic stenosis in 7%, and previous stroke in 5%. Ninety-one percent of patients had stenosis greater than 90% on arteriography. The perioperative stroke rate for carotid resection was 3.5%, with a subsequent rate of 0.0064 strokes per year. For repeat carotid endarterectomy, the perioperative stroke rate was 1.9% with a subsequent rate of 0.011 strokes per year. Graft patency after carotid resection was 93% (mean follow-up, 35 months). Four patients treated with carotid resection had graft thrombosis, and two of the four remained asymptomatic. After repeat carotid endarterectomy, one patient had carotid thrombosis, and recurrent stenosis greater than 50% developed in 23 patients (mean follow-up, 64 months). Twenty patients treated with repeat carotid endarterectomy underwent an additional operation for further symptomatic recurrent carotid stenosis. We conclude carotid resection is a safe and effective alternative to repeat carotid endarterectomy for patients undergoing operation for recurrent carotid stenosis. PMID- 1522638 TI - Maffucci's syndrome (hemangiomatosis osteolytica): a report of four cases. AB - Maffucci's syndrome is a congenital nonfamilial syndrome combining dyschondroplasia, (enchondromatosis) and hemangiomatosis. It is a rare disease; only 200 cases have been reported throughout the world in the past 140 years. Over the past 20 years, four patients have been admitted with signs and symptoms consistent with Maffucci's syndrome. Three were children ages 3, 7, and 9 years. The fourth was 23 years old. Two were male and two female. All had hemangiomas at birth, and all had skeletal deformities and enchondromas. All complained of pain and heaviness of the involved extremity. Three patients had the arterial inflow evaluated with arteriograms, and one had magnetic resonance imaging. Two also had venograms. Two patients had excision of their hemangiomas, and one had sclerotherapy and compression therapy. All had bone biopsies performed. None of the enchondromas or the soft tissue lesions had undergone sarcomatous transformation. PMID- 1522639 TI - Superiority of end-diastolic volume and ejection fraction measurements over wedge pressures in evaluating cardiac function during aortic reconstruction. AB - Marked changes occur in cardiac function during aortic reconstruction. Numerous factors (primarily compliance changes) limit the currently used pressure-based pulmonary artery catheters' ability to reflect these changes accurately. A new pulmonary artery catheter was used in 26 patients undergoing aortic reconstruction (7 patients with abdominal aortic aneurysms and 19 with occlusive disease) that directly measures right ventricular (RV) volumes and ejection fractions. The extent of coronary artery disease (CAD) was evaluated before surgery, and the patients were divided into three classes. The greatest changes in cardiac function were noted immediately after aortic cross-clamping. Cardiac output significantly decreased in patients with mild or moderate CAD (p less than 0.01 and p less than 0.001) but not in patients with no CAD (p less than 0.5). This correlated well with RV end-diastolic volume (RV-EDV) and stroke volume (RV SV) measurements in the groups with mild (p less than 0.05) and moderate CAD (p less than 0.01) but not in the group with no CAD (p greater than 0.5). Wedge pressure showed poor correlation, with no significant change noted in any group (p greater than 0.5). Measurements taken later in the procedure documented a significant trend toward baseline in mild and moderate groups. At the opening of the second limb of the graft, the compensated values (CO, RV-EDV, and RV-SV) did not change significantly in the groups with mild and no CAD (p greater than 0.2) but approached significance in the group with moderate CAD (p less than 0.08).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1522640 TI - Thoracoabdominal aortic aneurysms associated with celiac, superior mesenteric, and renal artery occlusive disease: methods and analysis of results in 271 patients. AB - Two hundred seventy-one of 1509 patients who underwent thoracoabdominal aortic repairs had either celiac or superior mesenteric or renal artery occlusive disease. These latter patients were treated by endarterectomy or bypass between June 20, 1960 and Jan. 10, 1991. After 1987, the 30-day survival rate was 93% (79 of 85) compared with 90% (245 of 271) before 1988. Multivariate predictors of death were age, postoperative reoperation for bleeding, and cardiac complications (p less than 0.05). Renal complications (13% dialysis, 35 of 271) were associated with preoperative renal dysfunction, elevated preoperative serum creatinine level, urine clearance time of dye, extent of the aorta replaced, coagulopathy, and paraplegia or paraparesis (p less than 0.05). The incidence of postoperative renal dysfunction was reduced by renal artery endarterectomy (p less than 0.05). On univariate analysis the risk of renal failure was reduced by renal artery perfusion with cold Ringer's lactate solution (p less than 0.05). Gastrointestinal complications (9%, 25 of 271) were associated with a history of peptic ulcer disease on multivariate analysis (p less than 0.05). The Kaplan Meier 5-year survival rates for patients with and without occlusive disease were 53% and 60%, respectively, and at 10 years 37% and 30%, respectively (p = 0.08). We conclude that endarterectomy or bypass of occlusive visceral disease reduces the risk of renal failure after thoracoabdominal aortic aneurysm repairs, does not decrease early or late survival, and does not increase the risk of gastrointestinal complications. PMID- 1522641 TI - Acute mesenteric ischemia after cardiopulmonary bypass. AB - Acute mesenteric ischemia is an uncommon but catastrophic event after cardiopulmonary bypass. From 1980 to 1990, 16,951 cardiac procedures requiring cardiopulmonary bypass were performed at Emory University Hospital in Atlanta, Ga. Eighteen patients (0.1%) had acute mesenteric ischemia that resulted in intestinal infarction. Emergency cardiac surgery had been performed in 16 of the 18 patients, and all 18 patients were vasopressor dependent for hemodynamic support after surgery. Diagnostic difficulties resulted in the diagnosis of intestinal infarction an average of 9 1/2 days after cardiopulmonary bypass. Nonocclusive mesenteric arterial ischemia was the determined cause in all cases. Statistically significant risk factors associated with acute mesenteric ischemia after cardiopulmonary bypass surgery included (1) emergency cardiac surgery (p less than 0.0001), (2) the use of an intraaortic balloon pump (p less than 0.0001), (3) failed angioplasty requiring emergency surgery (p = 0.0074), (4) prolonged pump time (p = 0.0093), and (5) advanced age (p = 0.0016). A high index of suspicion for mesenteric ischemia after cardiopulmonary bypass in patients with identified risk factors may decrease the diagnostic delay and lead to an improvement in the 67% mortality rate seen in this series. PMID- 1522642 TI - Are arteriograms necessary in penetrating zone II neck injuries? AB - The evaluation and management of potential arterial injuries in penetrating neck trauma are controversial. Routine surgical exploration or arteriography can be very expensive and time-consuming and can overburden available resources if used in all patients. We reviewed the records of 4035 patients seen in our trauma center during a 20-month period and identified a total of 110 patients (2.7%) with penetrating wounds to zone II of the neck; 50 were from gunshot wounds, 43 from stab wounds, 7 from shotgun injuries, and 10 from lacerations. In 42 (39%) patients there was no arteriogram or surgery based on location of the wounds or lack of any physical findings. None of these patients later had any evidence of an arterial injury. Forty-five patients (40%) had arteriograms based on proximity or a "soft" sign of vascular injury, which included evidence of significant bleeding or a stable hematoma. A total of 15 injuries to major arteries were identified: 3 common carotid, 5 internal carotid, and 7 vertebral. One patient died during initial resuscitation, and four patients went directly to surgery with no preoperative arteriogram for active bleeding and expanding hematoma (n = 1), an expanding hematoma (n = 2), and a large, stable hematoma (n = 1). Only one patient (of the 110) had a significant major arterial injury requiring surgery that was not predicted by physical findings. Nine arterial injuries were treated nonoperatively: six vertebral, two common carotid intimal flaps, and one small distal internal carotid pseudoaneurysm (diagnosed late). Three additional minor external carotid artery injuries were observed with no adverse sequelae.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1522643 TI - Recognition of arterial injury in elbow dislocation. AB - The clinical presentation of patients with elbow dislocations was reviewed to identify those factors indicating an increased risk for arterial injury. Sixty two patients were treated for 63 elbow dislocations between January 1981 and July 1991. Eight patients (13%) sustained a concomitant arterial injury involving the brachial (7) and radial (1) arteries. Three clinical findings, absence of a radial pulse, open dislocation, and presence of systemic injuries, were correlated with arterial injury. A palpable radial pulse was absent in six (75%) patients with an arterial injury but in only two (4%) with normal vessels (p less than 0.0001, chi square). Five (33%) open dislocations had an associated arterial injury, whereas three (6%) arterial injuries occurred in closed dislocations (p less than 0.006, chi square). Systemic injury occurred in five dislocations (63%) with arterial injuries and 14 dislocations (25%) without arterial injury (p less than 0.04, chi square). Multivariate analysis showed that absence of a radial pulse was the only factor that significantly predicted arterial injury (p less than 0.0001). Although most elbow dislocations are not associated with arterial injury, absence of a radial pulse or presence of an open dislocation or both should alert the clinician to the increased possibility of an associated vascular injury. PMID- 1522644 TI - The safety, efficacy, and durability of external carotid endarterectomy. AB - Results of 21 external carotid endarterectomies (ECEAs) in 19 patients with symptoms were reviewed retrospectively. No patients died or had new strokes referable to ECEA within 30 days of surgery. Overall, six (32%) patients died during an average 41 months of follow-up (range 1 to 134 months). Persistent symptoms followed five (71%) of seven ECEAs performed for cerebrovascular insufficiency or transient ischemic attacks. One patient treated urgently for an evolving stroke failed to improve and died after hospital discharge. Another patient with crescendo transient ischemic attacks had a preoperative deficit that did not resolve for 6 months and had a second stroke 2 years later. Another patient had a stroke after a contralateral carotid reconstruction but recovered. In contrast, only two (14%) of 14 ECEAs performed for monocular amaurosis fugax had persistent symptoms after surgery. Durability of 16 ECEAs was evaluated by arteriography or duplex scanning. Of six ECEAs closed primarily, three (50%) occluded, one has 60% restenosis, and only two (33%) had no restenosis (mean follow-up 36 months). Of 10 ECEAs closed by patch angioplasty, none occluded, 2 had 20% restenosis, and eight (80%) had no restenosis (mean follow-up 47 months). Life-table analysis indicated improvement in ECEA patency and durability with patch angioplasty (p = 0.011). From these data, ECEA can be performed with relative safety but is more effective for treatment of monocular amaurosis fugax in patients with a microembolic source at the external carotid origin. Patients with any other indications for ECEA did not benefit consistently from this operation. PMID- 1522645 TI - Is anticoagulation indicated for asymptomatic postoperative calf vein thrombosis? AB - The purpose of this study was to determine the effect of anticoagulation on the incidence of thrombotic propagation and pulmonary embolism in patients with calf vein thrombosis after total hip or total knee arthroplasty. Patients undergoing arthroplasties had prospective surveillance for postoperative deep vein thrombosis by both bilateral contrast venography and venous duplex scanning. Calf vein thrombosis was documented by venography in 42 patients (50 limbs), including 29 of 253 patients undergoing total hip arthroplasty (11.4%) and 13 of 99 patients undergoing total knee arthroplasty (13%). Of patients on whom follow-up duplex scans were performed, heparin followed by warfarin anticoagulation was used in 11 (13 limbs) and withheld in 21 (25 limbs). Propagation of thrombosis to the popliteal or superficial femoral vein or both was detected by serial duplex scanning in 3 of 13 treated limbs (23%) and 2 of 25 untreated limbs (8%), (p = 0.43). All thrombus propagations were detected within 2 weeks of the operative procedure. There were no pulmonary emboli or deaths. Propagation of asymptomatic calf vein thrombosis after arthroplasty was not influenced by anticoagulation, suggesting that postoperative calf vein thrombosis need not be routinely treated. Serial venous duplex scanning is useful to identify the occasional patient in whom thrombotic propagation requiring anticoagulation develops. PMID- 1522646 TI - The use of arm vein conduits during infrageniculate arterial bypass. AB - To further examine the use of arm vein for bypass to the popliteal or infrapopliteal arteries, we retrospectively reviewed 43 patients undergoing infrageniculate arterial bypass by use of an arm vein as a conduit. Nine grafts were done to the below-knee popliteal artery and 34 to the infrapopliteal arteries. Six grafts were done by use of a single segment of an arm vein, whereas 37 grafts were composites of either multiple segments of arm vein (n = 19) or segments of saphenous and arm vein (n = 18). Mean follow-up time was 15 1/2 months. Initial (30-day) graft patency and limb salvage were 95%. Primary graft patency by life-table analysis was 67% at 1 year and 49% at 3 years. Follow-up examination detected graft stenosis before occlusion in six patients (all of whom were given anticoagulant medication) and three failing grafts were salvaged. This increased overall 3-year secondary graft patency to 64% and 3-year secondary patency for infrapopliteal bypasses to 66%. Eleven of 12 graft occlusions resulted in major amputations (eight were above the knee, and three were below the knee) so that limb salvage paralleled secondary graft patency (63% at 3 years). Thus arm veins provide an excellent alternative venous conduit for infrageniculate arterial bypass, even when composite venous grafts must be used. PMID- 1522647 TI - Acute arterial thrombosis in the very young. AB - The case records of all infants under the age of 6 months who underwent surgery for acute arterial thrombosis between January 1980 and September 1991 were reviewed. Seven infants (nine ischemic limbs) were identified and ranged in age from 5 days to 5 1/2 months (mean 2.4 months); all weighed less than 5 kg (mean 3.9 kg). The cause in each case was iatrogenic. Diagnosis was based on the presence of a cool, mottled extremity associated with the absence of insonated peripheral arterial Doppler signals. Treatment included aortoiliac thrombectomy (n = 2), femoral artery thrombectomy with primary closure (n = 4), femoral artery thrombectomy with autogenous saphenous vein patch (n = 1), and axillary artery thrombectomy with end-to-end anastomosis (n = 1). Palpable pulses were restored in five (56%) of nine limbs and Doppler signals in the remaining limbs. There were no instances of limb loss. Excluding aortoiliac thrombectomy, palpable peripheral pulses were reestablished in only 40% of extremities. Thrombectomy is a safe and simple procedure in even the very youngest of patients with arterial insufficiency, but surgical optimism should be tempered by frequent inability to achieve full and durable success. PMID- 1522648 TI - Noninvasive detection of iliac artery stenosis in the presence of superficial femoral artery obstruction. AB - In patients with superficial femoral artery obstruction, iliac disease may be difficult to diagnose by commonly used noninvasive techniques. We studied common femoral artery acceleration time (onset of systole to peak systole), as measured from a Doppler spectral display and expressed in milliseconds. Previous work has suggested that an acceleration time of 144 msec or greater is abnormal and is associated with iliac stenosis (greater than or equal to 75% diameter reduction) or occlusion. During a 2-year period, in 139 limbs with superficial femoral artery obstruction, acceleration times were measured immediately before angiography. The overall test accuracy was 94.2% (131/139). In the 112 sides with normal angiograms, the acceleration time correctly identified no disease in 109 patients (97.3% specificity), and in the 27 iliac stenoses or occlusions the test detected disease in 22 patients (81.5% sensitivity). This appears to be a good test that can be done with equipment usually available in most vascular laboratories. PMID- 1522649 TI - Endovascular infrainguinal in situ saphenous vein bypass: a multicenter preliminary report. AB - The ideal operative approach for infrainguinal in situ bypass grafting would render the saphenous vein (SV) valves incompetent while occluding venous tributaries from within the SV: an endovascular in situ SV bypass. Forty-six femoropopliteal-tibial in situ bypasses were performed in part by the endovascular occlusion technique. Valvulotomy was accomplished with a retrograde "cutter" valvulotome, and endoluminal cannulation of 84 SV tributaries was performed with a shape memory metal alloy (nickle-titanium), electronically steerable catheter under angioscopic surveillance. Sixty-nine SV tributaries (82%) were totally occluded and 15 (18%) were partially occluded with platinum occlusion coils. Twelve coils that "recoiled" into the SV lumen were retrieved uneventfully. The valvulotomes caused six SV perforations that were repaired without consequence. Intraoperative fluoroscopy confirmed coil placement and verified venous tributary occlusion, as well as SV graft patency. During short term follow-up (mean 9.2 months; range 1 to 15 months), all patients have undergone ultrasonography of the in situ bypasses. All 69 of the SV tributaries that occluded initially have remained occluded and 84% (39/46) of the in situ bypasses have remained patent. This study demonstrates that an electronically steerable nitinol catheter can be used safely to occlude venous tributaries from within the SV. Endovascular occlusion of SV tributaries may ultimately obviate the need for long incisions the length of the leg, thus reducing wound-related problems and shortening recuperation. PMID- 1522650 TI - The effect of unilateral internal carotid arterial occlusion upon contralateral duplex study: criteria for accurate interpretation. AB - To determine the influence of unilateral internal carotid arterial occlusion (ICO) on Doppler frequency spectral analysis (DFSA) of the patent contralateral carotid artery, a retrospective review of 154 patients between July 1987 and December 1991 with angiographically confirmed ICO was performed, correlating duplex and arteriographic findings in a blinded fashion. Biplane arteriograms and bilateral carotid artery duplex studies that used a 5.0 MHz Doppler probe with a 1.5 mm3 sample volume at a 60 degree angle of insonation were performed on all patients. Each carotid artery was categorized by the severity of stenosis as quantified by arteriography: 1% to 15% (n = 41); 16% to 49% (n = 48), 50% to 79% (n = 21), 80% to 99% (n = 34), and bilateral occlusion (n = 10). DFSA peak systolic frequencies were commonly exaggerated in the presence of contralateral ICO and use of standard criteria for DFSA interpretation overestimated bifurcation stenoses in 43 of 89 lesions (48.3%) when determining nonhemodynamically significant lesions (less than 50% diameter reduction) with a sensitivity of only 57.3% and specificity of 96.9%. Conversely, prediction of hemodynamically significant lesions (greater than 50% diameter reduction) with standard criteria had 96.9% sensitivity but only 57.3% specificity. Modification of these criteria to account for the velocity increase or "jet effect" in the ipsilateral carotid artery system increased the sensitivity and specificity to 97.8% in predicting nonhemodynamically and hemodynamically significant stenoses respectively. A Doppler frequency spectrum with a peak systolic frequency (PSF) greater than 4.0 kHz and end-diastolic frequency (EDF) less than 5 kHz with an "open window" distinguished lesions with less than 50% diameter reduction.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1522651 TI - A new valvulotome for in situ bypass grafts. PMID- 1522652 TI - Factors affecting the patency of small-caliber prostheses. PMID- 1522653 TI - A new technique for reducing subcutaneous hemorrhage after stripping of the great saphenous vein. PMID- 1522654 TI - A technique for suturing anastomoses involving calcified vessels. PMID- 1522655 TI - Measurement of blood flow rates in the lower extremities with use of a nuclear magnetic resonance based instrument. PMID- 1522656 TI - A technique to prevent detachment of the Fogarty catheter from the Leather valve cutter during in situ bypass. PMID- 1522657 TI - Real-time color duplex scanning after sclerotherapy of the greater saphenous vein. PMID- 1522658 TI - Posttraumatic false aneurysm of axillofemoral bypass graft. PMID- 1522659 TI - A prospective, randomized trial of Unna's boot versus Duoderm CGF hydroactive dressing plus compression in the management of venous leg ulcers. PMID- 1522660 TI - Blood flow measurement with nuclear magnetic resonance technology: a clinically applicable technique? PMID- 1522661 TI - Carcinoma oesophagus. PMID- 1522662 TI - Oesophageal carcinoma in Karachi. AB - Between January, 1979 to August, 1990, 107 histologically proven cases of oesophageal carcinoma were seen. The ages of the patients ranged from 19-85 years (mean 55 +/- 14 years) with a male to female ratio of 1.2:1. Majority (70%) of the cases belonged to lower socioeconomic group and 56% were migrants from India. History of tobacco chewing or smoking was present in 78% cases. In 54%, the lesion was located in the middle third of the oesophagus, followed by lower third in 44%. Histology showed squamous cell carcinoma in 86% and adenocarcinoma in 10% cases. Of the 19 cases followed, 16 underwent surgery and 3 received chemotherapy. Two cases died within 7 months following surgery and in 6 carcinomas recurred. All cases receiving chemotherapy died within 8 months of treatment. PMID- 1522663 TI - Comparative study of single dose and five days dose of gentamicin as prophylaxis in appendicectomy. AB - One hundred patients who had appendicectomy for uncomplicated acute appendicitis over 1 year were randomly allocated to two groups of 50 patients each. Patients in group 1 had a single prophylactic injection of gentamicin while those in group 2 had a five days course with the first dose given just before the operation. There was no wound infection in any of the patients in either groups. There was also no statistically significant difference in the incidence of other postoperative complications. These findings suggest that a single prophylactic dose of gentamicin was as effective as a five days course in preventing postoperatively complications, like wound infection. PMID- 1522664 TI - Vulnerability factors for depression in Pakistani women. AB - The vulnerability factors were tested in a retrospective study on 50 cases and 50 controls. Only one of the four factors, i.e., lack of an intimate, confiding relationship, was found to be statistically significant, thus highlighting the need for indigenous research particularly in areas where the variables are socio culturally determined. PMID- 1522665 TI - Neuroblastoma of the kidney. PMID- 1522666 TI - Safety during bronchoscopy. PMID- 1522667 TI - [Fluorescence polarization immunoassay of isepamicin in blood spotted on filter paper]. AB - A simple method has been developed for the determination of the aminoglycoside antibiotic isepamicin (ISP) in whole blood, using dried blood spots (DBSs) on filter-paper. ISP in the DBSs were recovered most effectively in 0.5 M Na2HPO4 NaH2PO4 buffer (pH 7) by incubation for 30 minutes at 35 degrees C in an ultrafiltration tube. The eluates from the DBS papers were centrifuged at 3,000 x g for 10 minutes. The clear, colorless filtrates were transferred to an Abbott TDx cartridge for measurement by the fluorescence polarization immunoassay. The lower limit for the quantitative determination of ISP in the DBS was 2.5 micrograms per ml of whole blood. The method permits a simple collection of blood at a microliter level and should prove particularly useful for therapeutic drug monitoring of ISP in blood at effective levels in pediatric and geriatric patients. PMID- 1522668 TI - [In vitro study on efficacy of combination use of aspoxicillin and beta-lactam preparations (ceftazidime, cefmetazole and aztreonam) against bacteria isolated from abdominal infections]. AB - An in vitro study was done to evaluate combination use of aspoxicillin (ASPC) with each of 3 beta-lactam preparations, ceftazidime (CAZ), cefmetazole (CMZ) and aztreonam (AZT). The results obtained are summarized as follows: 1. ASPC has strong activity against Gram-positive bacteria and anaerobic bacteria, while CMZ and CAZ have strong activity against Gram-negative bacteria. 2. Rates of beta lactamase producing strains among the isolated bacteria (a total of 383 isolates) were 4.4% among Gram-positive bacteria, 71.6% among Gram-negative bacteria and 89.3% among anaerobic bacteria. The overall rate of beta-lactamase secreting strains among all isolates was 46.5%. 3. Efficacies of combination uses were studied using the FIC index. Combination of ASPC and CAZ was effective against 95.0% of the isolates, ASPC and AZT against 85.7%, and ASPC and CMZ against 83.5%. Combination of ASPC and CMZ showed antagonism in 12.8% of the isolates. In conclusion, combination use of ASPC with any one of CMZ, AZT or CAZ proved to be highly effective. In particular, combination of ASPC and CAZ appeared to be the best in view of complementing antibacterial spectra. PMID- 1522669 TI - [Antimicrobial activities of ceftriaxone against clinically isolated strains]. AB - Antibiotic activities (MICs) of ceftriaxone (CTRX) against 1,210 strains of bacteria including 28 spp. isolated in 1987 and 1990 were compared with those of other cephems. 1. When compared to data on clinically isolated strains reported in the early 1980s, strains of the following species isolated in 1990 showed extremely elevated MIC90s of CTRX: Staphylococcus spp., Streptococcus pneumoniae, Escherichia coli, Citrobacter spp., Enterobacter spp., Serratia spp., Proteus vulgaris, Morganella morganii and Providencia spp. No changes were observed in MIC90s between the 2 periods for microorganisms such as Streptococcus pyogenes, Haemophilus influenzae, Klebsiella pneumoniae, Proteus mirabilis and Peptostreptococcus spp. 2. The MIC90 of CTRX to S. pneumoniae was high because a large number of benzylpenicillin (PCG)-insensitive S. pneumoniae (PISP) was present among this species. The MIC80 to Bacteroides fragilis group was also high because highly resistant B. fragilis and B. thetaiotaomicron were isolated in large proportions among the bacteria of this group. Other oxime-type cephems also had high MICs against the above mentioned bacteria. Therefore, a further evaluation has to be made with regard to activities of oxime-type cephems such as CTRX against PISP and B. fragilis group. 3. Sample strains included, in high ratios, methicillin-resistant Staphylococcus aureus (MRSA), cephamycin-resistant as well as oxime-type cephem-resistant intestinal bacteria, Gram-negative bacteria, and new-quinolone-resistant bacteria. Some of there resistant bacteria are also CTRX-resistant, and CTRX had insufficient activities against them. 4. With regard to the assessment of changes of frequencies of specific drug resistant bacteria, including those with CTRX-resistance from year to year, the authors would like to point out the following comment of theirs made in 1989 and 1991, which appears to be increasing its significance, "Subjects of future studies should include dose on the mechanisms for the acquisition of bacterial resistance to entire beta-lactam antibiotics and the social circumstances in which resistant bacteria appear". 5. It appears that those strains resistant to cephems including CTRX are increasingly found among clinically isolated strains in recent years. CTRX, however, was found still effective against most clinical pathogens. Furthermore, considering that CTRX is one of the few drugs which sustain high blood concentrations of active forms we concluded that CTRX is a useful cephem-group antibiotic. PMID- 1522670 TI - [Clinical evaluation of combined therapy of ceftazidime and tobramycin for intractable pulmonary infection mainly caused by Pseudomonas aeruginosa]. AB - In an open, multicenter trial, we investigated the clinical efficacy of a combination therapy of ceftazidime (CAZ) and tobramycin (TOB) for intractable pulmonary infections mainly caused by Pseudomonas aeruginosa. Evaluated for the utility of the combination therapy were 33 cases with pneumonia (Group I: pneumonia caused by P. aeruginosa 15, Group II: pneumonia caused by other Gram negative bacilli 4 and pneumonia which causative organism was not determined 14) and 23 cases with chronic respiratory tract infection caused by P. aeruginosa. The results obtained are summarized as follows. 1. In Group I pneumonia, included 11 severe cases and 4 moderate cases, with a mean age of 69.3 years. Significant underlying diseases were present in 14 out of the 15 (93.3%): they included 10 cases of pulmonary diseases and 4 cerebrovascular diseases. The overall efficacy rate in these cases was 60.0%: but the efficacy rate in moderate cases was 100% and that in severe cases was 45.5%. 2. In Group II pneumonia included 16 severe cases and 2 moderate cases with a mean age of 68.2 years. Significant underlying diseases were present in 15 out of 18 (83.3%, all of the underlying diseases were pulmonary diseases) and the overall efficacy rate was 72.2% with 100% efficacy rate among moderate cases and 68.8% among severe cases. 3. In the cases with chronic respiratory tract infections caused by P. aeruginosa, the efficacy rate was 82.6% and the eradication rate was 65.2%. We consider the combination therapy of CAZ and TOB is useful for intractable pulmonary infections caused by P. aeruginosa. PMID- 1522671 TI - [Transferability of meropenem to cerebrospinal fluid in rabbits with meningitis caused by Staphylococcus aureus]. AB - The transferability of meropenem (MEPM) to cerebrospinal fluid (CSF) was studied employing rabbits with experimental meningitis caused by Staphylococcus aureus. The mean serum concentration was 93.1 +/- 13.5 micrograms/ml at 15 minutes after intravenous administration of MEPM at a dose level of 100 mg/kg. The mean concentration in CSF was maximum at 15 minutes after administration at 4.42 +/- 2.24 micrograms/ml. Pharmacokinetic parameters calculated from these values were as follows: Cmax (CSF/serum) 4.75%, AUC (CSF/serum) 10.4% between 15 and 60 minutes, 13.9% between 15 and 120 minutes and 15.7% between 15 and 180 minutes, T 1/2 for MEPM in CSF: 50.9 minutes, T 1/2 (CSF/serum): 2.19. In comparison to those of imipenem which were obtained in the same way, the transferability of MEPM was similar and in consideration of the antimicrobial potency against the main pathogens of meningitis, it appears worth-while of running clinical trials for this drug. PMID- 1522672 TI - [Clinical and pharmacokinetic evaluations of meropenem in children]. AB - Twenty-five children were treated with meropenem (MEPM, SM-7338) and the clinical efficacy and side effects were evaluated. Ages of the patients ranged from 9 months to 11 years. Dose levels of MEPM ranged from 50.4 to 108 mg/kg/day for 4 to 8 days. The 25 patients included 11 pneumonia cases, 4 bronchitis, 6 tonsillitis, 3 urinary tract infections and 1 gingivitis, and they were evaluated for the clinical efficacy of MEPM. Results were excellent in 13 and good in 12 patients. No side effects nor abnormal clinical laboratory test results were observed. The pharmacokinetics of MEPM was studied in 7 patients with ages ranging from 9 to 15 years. The mean plasma peak concentration of MEPM in 5 patients was 36.7 micrograms/ml after dosing 10 mg/kg, and that of 2 patients was 70.0 micrograms/ml after administering 20 mg/kg. These data showed that plasma concentrations of drug depended on dose levels. Average half-life values for the 2 groups (10 and 20 mg/kg) were 0.83 and 0.85 hour, respectively. Urinary recovery rates for the 2 groups (10 and 20 mg/kg) were 64.3% and 81.3%, respectively, in the first 5 hours after administration. PMID- 1522673 TI - [Clinical evaluation of meropenem in the pediatric field]. AB - A clinical study on a new carbapenem antibiotic, meropenem (MEPM), was carried out in acute pediatric infections. MEPM was administered to 8 patients including 3 patients with acute pneumonia, 2 with cervical lymphadenitis, 1 with acute tonsillitis, and 1 with cellulitis and 1 with sepsis. The overall efficacy rate was 100%. As an adverse reaction, diarrhea was observed in 1 patient. In clinical laboratory tests 1 patient was found to have S-GPT elevation which normalized after discontinuation of MEPM. MEPM appears to be effective and safe drug for pediatric acute infections. PMID- 1522674 TI - [Pharmacokinetic, bacteriological and clinical studies on meropenem in children]. AB - Pharmacokinetic, bacteriological and clinical studies on meropenem (MEPM) were performed in children. The results are summarized as follows: 1. A total of 16 patients was treated with MEPM. Each dose was 20 mg/kg, and administration was made 3 times daily using 30-minute intravenous drip infusion for 5-28 days. Clinical efficacies of MEPM in 16 patients with bacterial infections (1 with purulent meningitis, 1 with suspected subdural abscess, 2 with suspected sepsis, 4 with pneumonia, 1 with acute maxillar sinusitis, 2 with cervical abscess, 1 with acute gastroenteritis, 2 with skin soft tissue infection and 2 with urinary tract infection) were evaluated as excellent in 7 patients, good in 8 patients and fair in 1 patient with an efficacy rate of 93.8%. Fourteen causative organisms found in 11 patients (Streptococcus pneumoniae in 4, Branhamella catarrhalis in 3, Staphylococcus aureus in 3, Group B Streptococcus in 1, Escherichia coli in 3) were all eradicated. No adverse reactions were observed in any of the 16 patients. 2. MICs of MEPM against 6 clinically isolated bacteria (B. catarrhalis 2, S. pneumoniae 3 and S. aureus 1) from children with bacterial infections were examined. MEPM showed good antibacterial activities. 3. Pharmacokinetic studies: Peak plasma concentrations of MEPM averaged 43.07 micrograms/ml (37.20-46.30 micrograms/ml) at dose of 20 mg/kg administered by 30 minute drip infusion. In the first 8 hours after administration, the urinary excretion rates of MEPM averaged 39.9% of the administered dose.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1522675 TI - [Studies of meropenem in pediatric infections]. AB - Pharmacokinetic and clinical evaluations of meropenem (SM-7338, MEPM) were carried out in pediatric patients. The following results were obtained. 1. After 30-minute intravenous drip infusion at a dose of 20 mg/kg, plasma concentrations of MEPM reached their peaks at the end of drip infusion with an average value of 48.8 +/- 3.64 micrograms/ml, and the average plasma half-life was 0.93 +/- 0.21 hour in the beta-phase. After 30-minute intravenous drip infusion at a dose of 10 mg/kg, the average peak plasma concentration was 27.7 +/- 4.33 micrograms/ml and the average plasma half-life was 0.78 +/- 0.20 hour. 2. Urinary excretion rates of MEPM after 30-minute intravenous drip infusion at doses of 20 and 10 mg/kg were 44.8 +/- 4.54% and 40.9 +/- 1.78%, respectively. 3. MEPM was administered to 13 cases (upper and lower respiratory infections, pneumonia and lymphadenitis) at daily doses between 60-90 mg/kg/day divided into 3 dosages using 30-minute intravenous drip infusion. Clinical responses were "excellent" in 12 patients, "good" in 1, hence an efficacy rate of 100% was obtained. 4. Bacteria identified in various disease cases included 12 strains of 5 species, and the eradication rate was 100%. 5. No side effects were observed in any children. Laboratory test results showed abnormalities in 2 cases with elevations of GOT and GPT. These results suggest that MEPM may be a very useful and safe drug for the treatment of pediatric infections. PMID- 1522676 TI - [Clinical study on meropenem in pediatric field]. AB - We studied clinical effects of meropenem (MEPM, SM-7338), a newly developed parenteral carbapenem beta-lactam drug, and following results were obtained. The patients were administered with 16-20 mg/kg of MEPM every 8 hours using 1 hour drip infusion. 1. Clinical effects of MEPM were studied in 10 children with various infectious diseases: 1 with acute bronchitis, and 2 each with acute tonsillitis, acute bronchopneumonia, acute pneumonia, acute urinary infection, and 1 with pertussis pneumonia. The case of pertussis pneumonia later developed bronchiolitis obliterans, hence a steroid and gamma-globulin were used. This case was excluded from the clinical evaluation. The efficacy rate was 100% (9/9), and the bacteriological eradication rate was 100% (6/6). 2. No side effects were noted. Clinical laboratory test values were investigated in 10 patients. There was a case of abnormal laboratory test findings with mild elevations of liver functions such as GOT, GPT, and gamma-GTP. These abnormalities disappeared in 1 week after the end of therapy. PMID- 1522677 TI - [Pharmacokinetic and clinical studies on meropenem]. AB - Pharmacokinetic and clinical studies on meropenem (MEPM, SM-7338), a new developed carbapenem, were performed and the following results were obtained. 1. Absorption/excretion: Pharmacokinetics of MEPM was studied in 9 children using doses of 10 mg/kg and 20 mg/kg by a 30 minute-drip infusion. Peak plasma levels and plasma half-lives of the 2 doses were 28.4 and 43.0 micrograms/ml, and 0.70 and 0.80 hours, respectively. Their urinary recovery rates were 42.5 to 67.6% and 29.9 to 62.6%, respectively. Cerebrospinal fluid levels and penetration rates of MEPM in a patient with purulent meningitis were 0.66 to 4.01 micrograms/ml and 1.6 to 12.2%, respectively. 2. Clinical study: Forty-nine patients were treated with MEPM at doses exceeding 100 mg/kg/day with purulent meningitis and 30 to 60 mg/kg/day with other infections. MEPM gave "excellent" or "good" responses in 48 cases, an efficacy rate of 98.0%. Only one patient with subdural abscess showed fair response. Diarrhea and rash were observed in 1 case each. Abnormal laboratory test results were noted in 5 patients including elevation of GOT, GPT and eosinophils. In no cases the treatment had to be discontinued. PMID- 1522678 TI - [Clinical evaluation of a new carbapenem, meropenem, in infants and children]. AB - A new carbapenem antibiotic, meropenem (MEPM), was evaluated for its safety and efficacy in 33 infants and children. MEPM was effective in all the 32 evaluable cases including 4 cases of bacterial meningitis and 5 cases of Pseudomonas aeruginosa infections. The mean half life of plasma concentrations of MEPM was 0.84 +/- 0.09 hours after 30 minutes intravenous drip infusion. Mild diarrhea (2 cases), transient elevation of transaminases (8 cases), and transient eosinophilia (2 cases) were associated with the MEPM therapy, but none of them was problematic. These data suggest that MEPM is safe in infants and children and could be one of the therapeutic agents for severe infections or infections in compromised hosts. PMID- 1522679 TI - [Laboratory and clinical studies on meropenem in pediatrics]. AB - Laboratory and clinical studies on meropenem (MEPM), a new carbapenem antibiotic, were carried out in the field of pediatrics. The results obtained are summarized below. 1. The antibacterial activities of MEPM against clinically isolated organisms in our department were generally high. 2. After 30 minutes intravenous drip infusion of MEPM at a dose of 20 mg/kg to 2 children, the mean peak plasma level of MEPM was 32.7 micrograms/ml at the end of infusion with a mean half-life of 1.45 hours. The mean cumulative urinary recovery rate in the first 6 hours after infusion was 43.6%. 3. Fifteen patients with various bacterial infections were treated with MEPM. The clinical efficacy rate was 100% and the bacteriological efficacy rate was 95.2%. 4. No side effects were observed except in 1 case of mild diarrhea. Some abnormal laboratory test results were obtained, but they were mild with slight elevations of GOT and GPT in 2 cases. PMID- 1522680 TI - [Clinical studies of meropenem in pediatric field]. AB - We have carried out clinical studies on meropenem (MEPM, SM-7338), the results are summarized as follows. Treatment with MEPM was made in 13 cases of pediatric bacterial infections including 9 cases of pneumonia and 2 cases of colitis and 1 case each of purulent tonsillitis, and pharyngitis. Results obtained were excellent in 10 cases, good in 3 cases. No significant side effects due to the drug were observed in any cases, except in 1 case each of eosinophilia, elevated gamma-GTP, elevated total bilirubin and elevated GPT. PMID- 1522682 TI - [Legionella pneumophila infection and cellular immunity--interaction with immune cells]. PMID- 1522681 TI - [Studies on meropenem in the field of pediatrics]. AB - The pharmacokinetics and the clinical effectiveness of meropenem (MEPM) were examined in the field of pediatrics. The results are summarized as follows. 1. A 4-year-6-month-old girl with suppurative meningitis (Haemophilus influenzae) was treated by intravenous drip infusion of MEPM in a daily dose of 29 mg/kg which was divided into 4 dosages, each dosage being infused over 30 minutes, and the drug concentration in cerebrospinal fluid was determined. Upon completion of infusion on the 2nd day of treatment, the drug concentration was 2.52 micrograms/ml, which corresponded to 3.6% of the drug concentration in the blood. 2. MEPM was used in 10 patients, including 3 with suppurative lymphnoditis, 2 with staphylococcal scalded skin syndrome (SSSS) and 1 each with pneumonia, suppurative meningitis, suppurative knee arthritis, facial phlegmon and pyelonephritis. The daily doses ranged from 30 to 117.6 mg/kg, divided into 3 to 4 dosages and administered via intravenous drip infusion over 30 minutes. Clinical responses were evaluated as very good in 7 patients, good in 2 patients and fair in 1 patient, with an efficacy rate of 90%. 3. Isolated pathogens were 2 strains of Staphylococcus aureus, 1 strain of Klebsiella pneumoniae and 3 strains of Haemopilus influenzae. All of the 6 strains were eradicated, with an eradication rate of 100%. 4. In the safety evaluation, none of the patients was observed to have any side effects. Furthermore, no abnormal variations were found in laboratory test data possibly attributable to administration of MEPM. PMID- 1522683 TI - [Mechanism of T cell activation by bacterial exotoxins bearing superantigenic properties--relation to the toxin-induced pathologic reactions]. PMID- 1522684 TI - [An improved tetrazolium agar medium for testing sugar fermentation in lactobacilli]. AB - An improved tetrazolium agar medium for testing sugar fermentation in lactobacilli is described. Basal medium 86 was essentially a modified MRS broth with the omission of glucose. The standard formula was 30 micrograms/ml of 2,3,5 triphenyltetrazolium chloride, 2% sugar to be tested, and 2% agar in medium 86. Plates were incubated anaerobically for 2 days at 37C or 5 days at 30C, depending on the strain. With three strains each of group II and III lactobacilli, colorless, fermentation-positive colonies were clearly differentiated from red, fermentation-negative colonies. For three strains of group I lactobacilli, this medium was not satisfactory because they grew poorly on it unless supplemented with a sugar. PMID- 1522685 TI - Percutaneous coronary angioscopy. PMID- 1522686 TI - The occurrence of early sudden coronary artery occlusion following angioplasty may be predicted from the clinical characteristics of the patients and their coronary lesion morphology. AB - The aim of this study was to assess whether the incidence of early occlusion following angioplasty was greater among patients with unstable angina and whether the coronary lesions prone to early occlusion could be predicted from their angiographic appearance. Seventy-seven patients who had had a first angioplasty of a native vessel for stable or unstable angina in one twelve month period were included. The angiographic appearances of the angioplastied lesions were classified as either Type 1, which were smooth and unlikely to have thrombus or intimal rupture, or Type 2, which were irregular due to thrombus or intimal rupture. The lesion classification was compared to the patients' clinical features, i.e. stable or unstable angina, and the outcome of the angioplasty. Type 2 lesions occurred in 25% of patients with stable angina but 49% of patients with unstable angina (p less than 0.05). Early sudden occlusion of the angioplastied vessel occurred in 24% of patients with unstable angina but in only 3% of patients with stable angina (p less than 0.05) and in 6% of Type 1 lesions compared with 24% of Type 2 lesions (p less than 0.05). Thus it is possible to identify the clinical characteristics and angiographic appearances of those patients undergoing angioplasty who are most likely to experience early vessel occlusion. PMID- 1522687 TI - Safety and efficacy of a modified catheter-mediated ablation of accessory pathways. AB - Fifty-one consecutive patients underwent modified catheter-mediated direct current ablation of accessory pathways. Energy was delivered through the distal pair of electrodes (dual electrode configuration) of a 6F quadripolar catheter to the internal surface of the right or left atrioventricular (AV) annulus. In an attempt to prevent the later resumption of accessory pathway conduction, one additional shock was given after the initial successful interruption of accessory pathways. A mean of 2.7 shocks with cumulative energy of 453 +/- 32 Joules/patient interrupted the accessory pathways in 47 patients and modified the accessory pathway conduction in 2 patients. Forty-eight patients were asymptomatic and free of any antiarrhythmic agents with a follow-up ranging from 3-20 months (mean 12 +/- 1 months), without early or late serious complications (AV block or tamponade). Conduction characteristics, concealed or manifest, and recording of accessory pathway activity did not affect the outcome. Mean cumulative energy and number of applications of energy to achieve a successful outcome were lower in patients with concealed (376 +/- 31 Joules, 2.4 +/- 0.2 shocks) than manifest accessory pathways (516 +/- 50 Joules, 2.9 +/- 0.2 shocks). At the successful ablation sites, the mean shortest retrograde ventriculoatrial interval during orthodromic reentrant tachycardia (VA') was 80 +/- 3 msec (78% had VA' less than 90 msec) and was not different between concealed and manifest accessory pathways; the mean shortest antegrade AV interval was 47 +/- 3 msec in manifest preexcitation; the mean ratio of atrial to ventricular wave amplitude was not significantly different between left-sided (0.8 +/- 0.1) and right-sided (1.1 +/- 0.2) accessory pathways (p greater than 0.05). A successful outcome was achieved in 94% of 51 patients. This procedure is relatively safe and effective, regardless of the location of the accessory pathway. PMID- 1522688 TI - Fixed subaortic stenosis in childhood. Medical and surgical course in 90 patients. AB - This study evaluated diagnostic criteria, clinical observations, surgical indications and complications in 90 cases of fixed subvalvular aortic stenosis. Echocardiography, catheter angiography and surgical findings indicated that 60 (66.6%) patients had subvalvular membranous stenosis, 20 (22.2%) patients had fibromuscular stenosis, 4 (4.4%) patients had membranous and fibromuscular stenosis, and 6 (6.6%) had a tunnel-type obstruction. Forty-two patients had additional cardiac anomalies, such as PDA, valvular aortic stenosis and VSD. Fifty patients were treated surgically. Thirty-six patients were evaluated by two dimensional and Doppler echocardiography at post-surgical intervals ranging from 7 days to 11 years (mean 3.6 years). There were pathological echo findings in 12 patients. The prognosis of this anomaly depends upon early diagnosis and treatment. The results of this study support the importance of the two dimensional and Doppler echocardiography in early diagnosis and follow-up of the surgical results in treatment of this anomaly. PMID- 1522689 TI - Superiority of echocardiographically assisted blade atrial septostomy. AB - Blade atrial septostomy has been applied in 3 patients with transposition of the great arteries under two-dimensional echocardiography instead of fluoroscopy. The blade at the tip of the catheter was seen on an echo screen when it was in the left atrium. The blade was then extended and pulled slowly across the atrial septum from the left into the right atrium, under echocardiographic monitoring. The procedure was successful in all 3 patients. Interatrial communication measured echocardiographically was sufficient in size. Since the interatrial septum is clearly seen by means of echocardiography during blade atrial septostomy, the method is thought to be superior to fluoroscopy in the prevention of complications. PMID- 1522690 TI - Peripartum cardiomyopathy. AB - Peripartum cardiomyopathy is a relatively rare complication of pregnancy, characterized by heart failure of obscure etiology during the antepartal or postpartal period. During a 10-year period in our hospital, of 36,882 women who delivered, 6 were diagnosed as having peripartum cardiomyopathy. The incidence in our hospital was estimated as 1:6,147 deliveries. Among these 6 patients, 2 cases with fulminating courses died 1 month after treatment. Two other cases had cardiomyopathy and multiple congestive heart failure and died after 3 years and 6 years. Only one case, whose cardiac size returned to normal within 4 months, completely recovered from this disease. Another survivor with persistent cardiomegaly was followed for 5 years and remained clinically stable. In addition to congestive heart failure, the occurrence of complications such as sepsis, hepatorenal failure, and arrhythmia were the major causes of death. According to the results of our study, return of cardiac chamber size to the normal range indicated a good prognosis. We concluded that the prognosis of peripartum cardiomyopathy depends upon the degree of cardiac dysfunction and the response to therapy. PMID- 1522691 TI - Plasma t-PA/PAI-1 complex and blood coagulability in patients with coronary artery disease. AB - The t-PA/PAI-1 complex is a good indicator of the release of fibrinolysis activators and inhibitors from the vascular wall, but its clinical significance in chronic ischemic heart disease is unclear. The plasma levels of tissue-type plasminogen activator (t-PA), plasminogen activator inhibitor-1 (PAI-1), and the t-PA/PAI-1 complex (including various coagulation factors) were assayed in 72 patients with coronary artery disease (CAD) and 29 control (C) subjects. The CAD patients were subdivided into 3 groups: single-vessel disease (G1, n = 30), double-vessel disease (G2, n = 20), and triple-vessel disease (G3, n = 22). The patients with triple-vessel disease had higher fibrinogen values (G3: 318 +/- 75 mg/dl, C: 263 +/- 56), factor VII activity (G3: 143 +/- 36%, C: 123 +/- 14), and t-PA antigen levels (G3: 4.7 +/- 0.8 ng/ml, C: 3.3 +/- 0.7) than controls. Patients with double- and triple-vessel disease also showed higher levels of factor VIII, vWF antigen, thrombin-antithrombin III complex (G1: 2.3 +/- 0.6 ng/ml, G2: 2.7 +/- 0.5, G3: 3.1 +/- 0.5, C: 2.0 +/- 0.5), and t-PA/PAI-1 complex (G1: 13.9 +/- 6.1 ng/ml, G2: 16.4 +/- 4.6, G3: 18.2 +/- 5.9, C: 10.7 +/- 4.9) than control subjects. The t-PA/PAI-1 complex levels were correlated significantly with the activities of factors VII and VIII and the thrombin antithrombin III complex. These findings suggest that patients with CAD have greater blood coagulability than controls, and that this difference is related to the severity of the disease.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1522692 TI - Effects of clonidine on heart rate variability. AB - We compared the effects of intravenous infusions of clonidine and placebo on heart rate variability in 10 healthy male controls. Clonidine produced a significant decrease in blood pressure and significantly decreased the heart rate variability during quiet standing. PMID- 1522693 TI - Antiarrhythmic action of naloxone. Suppression of picrotoxin-induced cardiac arrhythmias in the rat. AB - The antiarrhythmic properties of the opiate antagonist naloxone have been reported in a variety of models of arrhythmia. To determine the generality and the possible central involvement of its antiarrhythmic activity, the effects of naloxone were assessed against cardiac arrhythmias induced by intravenous bolus injections of picrotoxin. Naloxone at doses of 0.33 and 1 mg/kg significantly reduced the incidence and severity of picrotoxin-induced arrhythmias in a dose related manner, without alteration of blood pressure and heart rate. The results demonstrate the antiarrhythmic efficacy of naloxone in an additional animal model. They further suggest that the antiarrhythmic actions of naloxone may be mediated by the central nervous system via both the autonomic and GABAergic pathways. PMID- 1522694 TI - A case of right atrial mobile thrombus complicating multiple pulmonary emboli. AB - Right atrial thrombi are usually immobile. However, a mobile type mimicking a cardiac tumor, especially myxoma, has been described on rare occasions. We report here a case of atrial thrombus which was mobile in the cardiac chambers. A 29 year-old male was admitted because of exertional dyspnea. On admission, his echocardiogram showed an abnormal mass in the right atrium with a stalk attached to the interatrial septum. It decreased in size on the next day. On the fourth day of admission, it moved to the right ventricle. Multiple pulmonary emboli were revealed by the lung perfusion scintigram. Two days after the administration of intravenous urokinase, the abnormal mass in the cardiac chambers was no longer seen on the echocardiogram. This was a rare case of mobile atrial thrombus associated with multiple pulmonary emboli. Thrombolytic therapy appeared to be effective in this case. PMID- 1522695 TI - Successful transseptal catheter electrical ablation of sustained ventricular tachycardia of possible intramuscular origin. AB - Low-energy electrical ablation at 100 joules was attempted via a catheter in a patient with sustained ventricular tachycardia (VT) refractory to drug therapy. The patient was a 17-year-old woman who had undergone complete surgical correction of a double outlet right ventricle at the age of 9. The first episode of VT appeared at the age of 17. It was refractory to procainamide and lidocaine and it was sustained until termination with direct countershock. Two different QRS morphologies of VT were documented in the electrophysiologic study and one was identical to the VT observed in the clinical course. Conventional drug therapy failed to prevent induction of VT and catheter electrical ablation was attempted. The earliest activation site during the clinical episode of VT was localized to the right ventricular side of the interventricular septum (site 14 15), but pacing from this site resulted in a slightly different QRS morphology from that of VT. At the left ventricular side of this site (site 2), pacing during VT resulted in a QRS morphology identical to that of VT but the electrogram of this site did not precede the onset of the surface QRS complex. From these findings, the origin of VT was considered to be in the muscular layer of the interventricular septum. The method of transseptal shock using two catheters was applied and direct countershock at 100 joules successfully ablated the VT. PMID- 1522696 TI - Enhancing program implementation and maintenance through a multiphase approach to peer-based staff development. AB - School-based health education programs often are limited by failures in implementation and maintenance. While inservice training has proven beneficial, teacher training research indicates that the more complex the demands on teachers using innovative psychosocially based health education curricula, the greater the necessity for post-inservice follow-up staff development. Evidence is presented that 1) teachers respond to innovations in developmental stages, 2) a multiphase approach to staff development is necessary to assist teachers during each stage, 3) post-inservice staff development requires opportunities for teacher collaboration, 4) approaches to staff development should fit the stage of teacher development, and 5) the organizational context of staff development is critical. Peer-based approaches to post-inservice staff development are presented, with a review of strengths and limitations of each approach. PMID- 1522698 TI - Indicators of substance use among pregnant adolescents in the Mississippi Delta. AB - Data were collected from 293 pregnant adolescents living in the southern Illinois section of the Mississippi Delta region concerning their substance use behaviors in 1989 and 1990. Subjects used a variety of drugs in the past and present. For example, 24.4% of the sample reported they presently smoked cigarettes. Alcohol was used by 20.4% in the previous five months, while 5.2% reported marijuana use during the same period. Regression models designed to predict substance use produced adjusted r2 values of .30 (SE = 1.06) for cigarette use, .38 (SE = .49) for marijuana use, and .43 (SE = .59) for alcohol use. Significant indicators included peer and personal substance use behavior, parental substance use, and having previously received mental health treatment. PMID- 1522697 TI - Adolescent health: a report to the U.S. Congress. AB - This article reports findings from an assessment by the Office of Technology Assessment (OTA), an analytical arm of the U.S. Congress. In brief, OTA found the conventional wisdom that American adolescents as a group are so healthy that they do not require health and related services is not justified. Even more disturbing, U.S. adolescents often face formidable barriers in trying to obtain health care. OTA suggested that Congress could act to 1) increase adolescents' access to health care, most effectively by supporting school- or community-based comprehensive health services specifically for adolescents, 2) restructure and reinvigorate the federal role in adolescent health, most visibly by creating an office of adolescent health in the U.S. Executive branch, and 3) improve adolescents' social environments, by providing more support to the families of adolescents, limiting adolescents' access to firearms, supporting the expansion of recreational opportunities for adolescents, and further supporting opportunities for community service. Congressional actions taken since the release of OTA's report are summarized. PMID- 1522699 TI - Nutrient contribution of the school lunch program: implications for healthy people 2000. AB - Cardiovascular disease-related nutrients were quantified in a school lunch program over a 15-year period. Methods included 24-hour dietary recall, menu weights, and recipe analysis. School lunch was eaten by 93% of students. School lunches provided 23% of daily kilocalories and 24%, 29%, and 20% of daily fat, protein, and carbohydrate intake, respectively, saturated fat and cholesterol from school lunch were 27% and 24% of daily total. School lunch provided 7% of daily sucrose and 32% of daily sodium. Children not eating school lunch had significantly greater polyunsaturated (p less than .001), carbohydrate (p less than .05), and sucrose (p less than .001) intakes. Though the school lunch contributed less than one-third of daily total nutrients, intakes of diet components related to cardiovascular disease risk were excessive. Sixty percent to 80% of children exceed daily total fat, saturated fat, cholesterol, and sodium intakes over recommended levels. Schools can influence childhood cardiovascular disease risk by providing students healthier foods, with education to promote positive lifestyles. PMID- 1522700 TI - Adolescents' reasons for smoking. AB - Part of the Hutchinson Smoking Prevention Project, this study provides information on reasons reported by adolescents for their smoking behavior. A total of 1,615 10th grade students in 20 rural and suburban school districts in Washington state were asked why they currently smoke and why they first smoked. For beginning smoking, curiosity, social norms, and social pressure were the most frequently given reasons for smoking. For current smoking, pleasure and addiction were mentioned most often. A number of gender differences occurred with 10th grade students beginning and current smoking. More females than males reported social norms and social pressure as reasons for beginning to smoke, whereas for currently smoking, pleasure was given as a reason more frequently by females than males. When developing interventions, smoking prevention programs need to consider students' current and past smoking behavior, and the reasons they give for smoking. PMID- 1522701 TI - Floating down the river of life. PMID- 1522702 TI - An AIDS prevention program for adolescents with special learning needs. PMID- 1522703 TI - The 1991 report of the National Commission on AIDS. PMID- 1522704 TI - An evaluation of sample preparation techniques for the GC/MS analysis of urinary mercapturic acid conjugates. AB - Recovery rates of four different techniques for the preparation of human urine samples spiked with N-acetyl-S-benzyl-L-cysteine (BMA) were compared at three different spiking levels. At concentrations of 1,000 ppm and 1 ppm in the urine, recoveries of BMA were greatest (80-96%) using an ion pair phase transfer technique and a C18 solid-phase extraction (C18) technique while an acidic ethyl acetate extraction method yielded 67-69% recoveries and a quaternary amine solid phase extraction technique showed poor recoveries (5-7%). At 10 ppb, quantitative recovery could only be determined for the C18 technique due to interferences from samples prepared using the other three techniques. The results indicate that the C18 sample preparation technique followed by GC/MS analysis using stable isotopically labeled internal standards provides a rapid and accurate method for quantitation of mercapturic acids at low-ppb levels in the urine. PMID- 1522705 TI - Collection and handling of clinical blood samples to assure the accurate measurement of cocaine concentration. AB - The measurement of serum cocaine concentration is difficult because it is rapidly metabolized in vivo and in vitro. Previous investigators have used sodium fluoride (0.5-3.0%) in an attempt to stabilize its concentration in samples of whole blood, but these concentrations of sodium fluoride are not readily available outside the analytical laboratory. This study was performed to assess the stability of cocaine in whole blood when stabilized in a commonly available concentration of sodium fluoride (0.25%), with or without concomitant refrigeration. Whole blood was enriched with cocaine to a final concentration of 900 ng/mL and added to flasks containing sodium fluoride (0, 0.25, 0.5, and 1.0%) or 0.25% sodium fluoride plus potassium oxalate (gray-top Vacutainer tubes), after which it was stored at 4 degrees C or at room temperature. Whole blood cocaine concentrations were measured at 0, 24, and 48 h by gas chromatography. Sodium fluoride at all concentrations, with or without refrigeration and potassium oxalate, effectively inhibited cocaine degradation, with 86-91% of the drug present after 48 h. In contrast, substantial degradation of cocaine occurred in the samples stored without sodium fluoride, regardless of temperature. Thus, the use of commercial gray-top Vacutainer tubes effectively stabilizes cocaine in blood during procurement, transport, and short-term storage. PMID- 1522706 TI - Comparative kinetics of digoxin in serum and vitreous humor in a guinea pig model. II. Single oral dose administration. AB - In a continuation of work previously reported involving the comparative kinetics of digoxin in vitreous humor and serum after an intravenous dose, the present report describes the pharmacokinetics of digoxin in this model following the administration of a single oral dose. Serum and vitreous humor concentrations of digoxin were monitored by radioimmunoassay for 720 min after a single oral dose of 0.1 mg digoxin/kg. Serum concentrations peaked by 60 min and declined over the remaining observation period with a half-life of 360 min. Vitreous humor concentrations lagged behind the serum concentrations, peaked between 60 and 120 min, and then declined at a rate less than that of serum with convergence of concentration occurring in the 720-min samples. The vitreous humor-serum ratios ranged from a low of 0.003 (15 min) to a high of 0.98 at convergence. The impact of these findings upon forensic toxicologic practice is reviewed. PMID- 1522707 TI - The certification of cocaine and benzoylecgonine in a human urine standard reference material. AB - The concentrations of cocaine and benzoylecgonine (BE) in Standard Reference Material (SRM) 1508, cocaine and metabolites in freeze-dried human urine, were determined at the National Institute of Standards and Technology (NIST, formerly NBS) by two independent methods. For cocaine, one method was based on gas chromatography/mass spectrometry (GC/MS); the other was based on high-performance liquid chromatography (HPLC). For BE, one method was based on GC/MS; the other was based on flow injection analysis/thermospray mass spectrometry (FIA/MS). The results for each pair of methods were statistically evaluated. Concentrations were determined in the SRM for three levels of cocaine and three levels of benzoylecgonine. Methylecgonine, although present in the material, was not determined. For cocaine, the concentrations were 90, 263, and 429 ng/mL of human urine. For BE, the concentrations were 103, 259, and 510 ng/mL of human urine. PMID- 1522708 TI - Rapid isolation with Sep-Pak C18 cartridges and wide-bore capillary gas chromatography of bromisovalum. AB - A simple and rapid method for isolation of bromisovalum with Sep-Pak C18 cartridges from human whole blood, plasma, and urine containing allylisopropylacetylurea as an internal standard, is presented. Detection of the drugs was made by nonpolar wide-bore capillary gas chromatography (GC) with flame ionization. The drug-containing samples, after mixing with water, were directly applied to the cartridges and eluted with chloroform-methanol (9:1). The recoveries of bromisovalum with use of the cartridges were excellent. Bromisovalum and internal standard allylisopropylacetylurea could be satisfactorily separated from each other and from impurities with the wide-bore capillary column. The detection limit for bromisovalum was 2-5 ng in an injected volume. PMID- 1522709 TI - Diethyl ether interference with infrared breath analysis. AB - Diethyl ether vapor may substantially interfere with breath alcohol analysis by instruments based on infrared absorption at 9.5 microns. Exposure of two volunteers simultaneously to diethyl ether vapor for one hour followed immediately by breath tests on the Draeger Alcotest 7110, Siemens Alcomat V5.2F, and Seres Ethylometre 679T produced apparent alcohol readings in one subject of 0.4, 0.1, and 0.1 g/100 mL of blood respectively. Positive readings persisted in this subject for more than 3 hours. The second subject produced much lower readings of 0.03, 0.01, and 0.00, respectively. Readings persisted with the Alcotest 7110 for one hour. Gas chromatographic analyses of blood and breath samples confirmed that these readings were caused by diethyl ether and not ethanol. The blood concentration of diethyl ether in Subject A immediately after exposure was 25 mg/L. This level produced no clinically detectable neurological changes in the subject. PMID- 1522710 TI - Determination of arsenic in fish by hydride generation atomic absorption spectrometry. AB - A method utilizing microwave dissolution in a closed Teflon bomb followed by hydride generation atomic absorption spectrometry has been used for the routine analysis of arsenic in fish species from the coast of the province of Granada, Spain. The technique was evaluated for decomposing biological standard reference material (BCR mussel tissue) for arsenic analyses. The precision of the results ranged from 2.78 to 6.99%. The recovery percentages ranged from 96.33 to 100.00%. The values determined in the samples indicated slight contamination by this element in the zone. The concentrations of arsenic in fish ranged from 0.396 to 45.716 micrograms/g. PMID- 1522711 TI - Screening for drugs of abuse with the Roche ONTRAK assays. AB - A family of manual, qualitative, latex agglutination inhibition immunoassay screening tests (ONTRAK, Roche) for amphetamines, barbiturates, cocaine, marijuana, morphine, and phencyclidine were evaluated. The assays are inexpensive, rapid, portable, and easy to perform, requiring little training to obtain proficiency. The tests are sensitive to drug concentrations at or around the stated cutoff values. The ONTRAK results agree well with the results obtained from fluorescence polarization immunoassay (FPIA) or radioimmunoassay (RIA) screening and GC/MS confirmation. Potential drawbacks of the test kits include the subjective nature of the qualitative assays and the lack of a positive control. The ONTRAK system provides a reasonable means of conducting field testing for drugs of abuse. PMID- 1522712 TI - Gas chromatographic determination of 2,5-hexanedione in urine as an indicator of exposure to n-hexane. AB - A sensitive and specific method for determination of 2,5-hexanedione in urine is described. Treatment of the urine specimen directly with n-butylamine yields n butyl 2,5-dimethyl pyrrole. The latter is extracted into diisopropylether and analyzed by gas chromatography (GC) with flame ionization detection (FID), thermionic specific detection (TSD) (N mode), or mass spectrometric detection (MS). The minimum detectable quantities are 1 mg/L urine when employing FID with a coefficient of variation of less than 6%. Recovery of 2,5-hexanedione added to the urine at the level of 10 mg/L was 78.9%. PMID- 1522713 TI - Rapid high-performance liquid chromatographic assay of chlorophacinone in human serum. AB - A simple procedure for the determination of chlorophacinone in human serum by high-performance liquid chromatography is reported. After addition of a suitable internal standard, unknown samples were extracted at acid pH with ethyl acetate. The reconstituted methanolic extract was directly injected into the liquid chromatograph. Separation was performed with a Lichrospher C18 5-microns column with a methanol-phosphate buffer (85:15, v/v) mobile phase. The eluent was monitored with UV detection at 286 nm. The method was found to be sufficiently rapid, reproducible, selective, and sensitive for use in clinical and experimental pharmacokinetic studies. Application of this method to 20 intoxicated patients indicated that the risk of bleeding syndrome, which is always associated with this kind of intoxication, is no longer present when chlorophacinone levels drop to below 1 microgram/mL. PMID- 1522714 TI - Determination of 3-quinuclidinyl benzilate (QNB) and its major metabolites in urine by isotope dilution gas chromatography/mass spectrometry. AB - In response to the scheduled destruction of U.S. military stockpiles of the hallucinogenic agent 3-quinuclidinyl benzilate (QNB), a specific confirmatory test for human exposure to QNB was developed. The amount of the parent compound in the urine as well as the two major metabolites, 3-quinuclidinol (Q) and benzilic acid (BA), was determined because the relationship between QNB dose and levels of QNB and its metabolites in human urine is not known. QNB was determined in urine samples spiked at a target level of 0.5 ng/mL, and the metabolites BA and Q were determined at a target level of 5 ng/mL. The method uses solid-phase extraction to isolate each analyte from the urine and isotope dilution gas chromatography/mass spectrometry for quantitation. Each analyte is converted to its trimethylsilyl derivative for analysis. The analytical method was tested on eight different urine samples spiked with known amounts of the analytes near the target levels, at 10 times the target levels, and blank (unspiked) urine samples. The variabilities in the method are for the most part evenly distributed between three imprecision categories: GC/MS measurement, sample preparation, and the urine samples. The total imprecision (1 standard deviation) of a single measurement is about 15% of the value for each analyte. PMID- 1522715 TI - The effect of pralidoxime chloride in the assay of acetylcholinesterase using 5,5'-dithio-bis(2-nitrobenzoic acid) (Ellman's reagent). AB - Pralidoxime chloride (PAM) hydrolyzes acetylthiocholine, the substrate used in the assay of red cell cholinesterase. The thiocholine that is produced forms a yellow complex when Ellman's reagent is used in the assay. This was tested in blood samples of patients who were treated with PAM after organophosphorus (OP) poisoning and after the observation of an immediate increase in absorption of light at 412 nm. PMID- 1522716 TI - Detection of diuretics in horse urine by GC/MS. AB - The use of diuretics in horses subject to doping control is prohibited. Thus, a sensitive screening procedure is required to identify the chemically different diuretics. We communicate here a method to detect three commonly employed acidic diuretics: bumetanide, ethacrynic acid, and furosemide. A liquid-liquid extraction on Extrelut 3 was performed at weak acidic and basic conditions using ethyl acetate as organic solvent. For analysis by GC, the diuretics were methylated on-column in the presence of MSTFA/TMAH, avoiding the commonly employed highly toxic derivatizing agent methyl iodide. For identification of diuretics, we used a mass selective detector operating in the SIM (selected ion monitoring) mode. Confirmation analysis may be obtained with a full scan run. Recoveries for the individual drugs ranged from 31 to 48% at the 100-ng/mL level for 3 mL urine, using calibration curves of drug standards with linearity from 2.5 to 20 ng injected. The limit of detection amounts to 40 ng/mL for the three diuretics. The method permits rapid and sensitive detection of diuretics in horse urine and is recommended for doping control. PMID- 1522717 TI - Cocaine and metabolite concentrations in the hair of South American coca chewers. AB - Hair samples obtained from South American Indians who were identified as daily chewers of coca leaves were analyzed by a sensitive gas chromatography/mass spectrometry (GC/MS) method for cocaine, benzoylecognine (BE), and ecognine methyl ester (EME). The mean cocaine concentration in the hair of these five subjects was 15.2 ng/mg hair +/- 11.0 (range = 1.0-28.9 ng/mg), mean BE concentration was 2.8 +/- 1.6 ng/mg hair (range = 0.3-4.4 ng/mg hair), and mean EME concentration was 1.6 +/- 1.7 (range = 0.0-4.4 ng/mg hair). The finding that cocaine was present at approximately 5 times higher concentration than BE and approximately 12 times higher than EME is surprising in light of the much longer plasma half lives of these metabolites. Washing the hair before analysis with 1% dodecyl sulfate, methanol, and distilled water reduced the concentration of cocaine in the hair but also reduced the concentrations of the metabolites. These data suggest that factors other than the drug concentration in blood may be important in determining the amount of drug incorporated into hair. PMID- 1522719 TI - Identifying components of variability in breath alcohol analysis. PMID- 1522718 TI - Evaluation of full-scanning GC/ion trap MS analysis of NIDA drugs-of-abuse urine testing in urine. AB - Analytical methods developed for the Finnigan MAT ITS40 gas chromatograph-ion trap mass spectrometer (GC/MS) were evaluated for the confirmation of drugs-of abuse in urine. The specific drugs evaluated are those listed by the National Institute on Drug Abuse (NIDA): 11-nor-9-carboxy-delta 9-tetrahydrocannabinol (9 carboxy-THC), benzoylecgonine (BE), codeine and morphine, phencyclidine (PCP), amphetamine, and methamphetamine. Drugs were extracted from urine using solid phase columns, separated by capillary gas chromatography, and analyzed by ion trap mass spectrometry following electron impact ionization. All drugs except PCP were derivatized prior to analysis. The full scan limits of detection (LOD), quantitation (LOQ), and linearity were 2.5, 5.0, and 1000 ng/mL, respectively, for 9-carboxy-THC; 37, 75, and 5000 ng/mL for BE; 50, 100, and 2500 ng/mL for the opiates; 0.25, 0.50, and 500 ng/mL for PCP; and 50, 100, and 5000 ng/mL for the amphetamines. The limits of detection (LOD) and limits of quantitation (LOQ) met the minimum criteria for the signal-to-noise (S/N) ratio and spectral match criteria for drug identification. Absolute LODs and LOQs (in ng/mL) for the ITS40 based on single ion monitoring of blank urines were: 0.8 and 2.0 for 9-carboxy THC; 8.9 and 25 for BE; 3.3 and 9.6 for codeine; 6.2 and 16.7 for morphine; 0.25 and 0.32 for PCP; 0.7 and 2.0 for amphetamine; and 2.4 and 5.7, for methamphetamine, respectively. The coefficient of variation ranged from 5 to 10%, and analytical recoveries were in the range of 90-114%. The ion trap mass spectrometer permits full scan identification of drugs while maintaining analytical LOQ that are below NIDA guidelines, and has equivalent or better detection limits to quadrupole analyzers for high sensitivity applications. PMID- 1522720 TI - Vascular fluid mechanics, the arterial wall, and atherosclerosis. AB - Atherosclerosis, a disease of large- and medium-size arteries, is the chief cause of death in the United States and in most of the western world. Severe atherosclerosis interferes with blood flow; however, even in the early stages of the disease, i.e. during atherogenesis, there is believed to be an important relationship between the disease processes and the characteristics of the blood flow in the arteries. Atherogenesis involves complex cascades of interactions among many factors. Included in this are fluid mechanical factors which are believed to be a cause of the highly focal nature of the disease. From in vivo studies, there is evidence of hemodynamic influences on the endothelium, on intimal thickening, and on monocyte recruitment. In addition, cell culture studies have demonstrated the important effect of a cell's mechanical environment on structure and function. Most of this evidence is for the endothelial cell, which is believed to be a key mediator of any hemodynamic effect, and it is now well documented that cultured endothelial monolayers, in response to a fluid flow imposed laminar shear stress, undergo a variety of changes in structure and function. In spite of the progress in recent years, there are many areas in which further work will provide important new information. One of these is in the engineering of the cell culture environment so as to make it more physiologic. Animal studies also are essential in our efforts to understand atherogenesis, and it is clear that we need better information on the pattern of the disease and its temporal development in humans and animal models, as well as the specific underlying biologic events.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1522721 TI - Topographical mapping of sites of enhanced HRP permeability in the normal rabbit aorta. AB - The spatial distribution of sites of enhanced permeability to the macromolecule horseradish peroxidase (HRP) in the normal rabbit aorta after one min circulation was studied using image analysis. These sites, referred to as "HRP spots," exhibit a nonuniform distribution that is qualitatively similar in all rabbits studied. The density of HRP spots is highest in the aortic arch, decreases distally, reaches a minimum in the lower descending thoracic aorta, and then increases again in the abdominal aorta. The region of highest spot density follows a clockwise helical pattern in the aortic arch and outside the arch occurs in streaks largely oriented in the bulk flow direction. The streaks in the abdominal aorta localize along the anatomical right lateral wall and occasionally along the left lateral wall proximal to the celiac artery and along the ventral wall between the celiac and superior mesenteric arteries. The density of spots is high in the immediate vicinity of aortic ostia with the most elevated density being distal to ostia in most cases. At a short distance from the ostium edge of the celiac and superior mesenteric branches the proximal density is comparably high, and no preferred spot orientation is observed around the brachiocephalic vessel. These results are consistent with an influence of localizing factors such as detailed hemodynamic phenomena and/or arterial wall structural and/or functional variations. PMID- 1522723 TI - Endothelial cell morphometry of atherosclerotic lesions and flow profiles at aortic bifurcations in cholesterol fed rabbits. AB - Observations on shapes of endothelial cells both in sudanophilic and nonsudanophilic regions at bifurcations of the brachiocephalic (BC) and left subclavian (SA) arteries in hyperlipidemic rabbits were performed under a SEM. The stagnation point of flow and leading edges of flow dividers were nonsudanophilic and covered by round and long fusiform endothelial cells, respectively. The hips of flow dividers of both branchings, proven to be relatively low shear stress regions, by movement of microspheres in steady flow, were sudanophilic and covered by ellipsoidal cells. Similar studies were carried out in normolipidemic rabbits. It might be concluded that lipid deposition in hyperlipidemic rabbits occurs in relatively low shear stress regions, where endothelial cells are functionally activated, rather than in laminar high shear stress regions at the flow divider. PMID- 1522722 TI - The polyelectrolyte properties of elastin. AB - The charge structure and ionic interactions of elastin prepared from the pig thoracic aorta by acid, alkali, or CNBr extraction have been investigated by potentiometric titration and radiotracer techniques. The number of charged groups was consistent with the amino acid composition, comparable to elastin from other sources and insensitive to the method of preparation. The enthalpies of ionization of the basic groups were comparable for those previously found for proteins but those of the acidic groups were higher. Ionic interactions were predominantly electrostatic although a strong affinity for chloride ions was noted. Changes in ionic interactions as the elastin was stretched had a similar effect to an increase in the apparent fixed charge density of the tissue. Mechanical strain altered the protonation of the elastin and the pK of the carboxyl groups. Conversely, the conformation of the elastin network varied with ionic strength and pH, being particularly sensitive to the degree of ionization of the more basic groups and with the ionic strength and anion composition of the medium. We speculate that strain induced changes in the conformation of elastin altering its reactivity towards lipids, ions or matrix macromolecules or changes in its mechanical properties resulting from changes in its ionic environment may be of physiological or pathological importance. PMID- 1522724 TI - The distribution of fluid forces on model arterial endothelium using computational fluid dynamics. AB - Numerical calculations are used in conjunction with linear perturbation theory to analyze the problem of laminar flow of an incompressible fluid over a wavy surface which approximates a monolayer of vascular endothelial cells. These calculations model flow conditions in an artery very near the vessel wall at any instant in time, providing a description of the velocity field with detail that would be difficult to identify experimentally. The surface pressure and shear stress distributions are qualitatively similar for linear theory and numerical computations. However, the results diverge as the amplitude of surface undulation is increased. The shear stress gradient along the cell model surface is reduced for geometries which correspond to aligned endothelial cells (versus nonaligned geometries). PMID- 1522725 TI - Convective mass transfer effects on the intracellular calcium response of endothelial cells. AB - Endothelial cells, which line the vasculature, respond to specific agonists such as adenosine triphosphate (ATP) by elevating cytosolic calcium levels and increasing production of the vasoactive compounds, prostacyclin and endothelial derived relaxing factor (EDRF). Endothelial cells express ecto-enzymes which metabolize ATP. If the activity of these enzymes is sufficiently high, then the concentration of ATP near the endothelial cell surface can be substantially lower than the bulk concentration. The ATP concentration is determined by a balance between the convection of fresh ATP from upstream and the degradation of ATP by the endothelial cells. In this report, we present a parallel plate flow system for measurement of cytosolic calcium levels ([Ca2+]i) of individual bovine aortic endothelial cells with the calcium sensitive fluorescent dye, fura-2. The cells respond to increases in the flow rate by increasing [Ca2+]i if there is ATP present in the perfusing buffer, but not in the absence of ATP. The amount of agonist in the perfusing fluid near the endothelial cell surface is estimated by solving the governing differential equation for the concentration profile of ATP in the parallel plate flow geometry. The solution indicates that one mechanism endothelial cells may use to detect changes in the flow rate is to respond to the change in the local concentration of agonist. PMID- 1522726 TI - Computer simulation of occupant neck response to airbag deployment in frontal impacts. AB - A mathematical simulation was performed to study the potential of head and neck injury to an unbelted driver restrained by an airbag. The baseline study represented a 50th percentile male dummy driving in a compact car with the steering wheel perpendicular to the floor. The vehicle was moving at 48 km/hour at the time of impact. Model predictions were compared with sled test results. The data agreed reasonably well. A parametric study was performed to study the effect of changing the steering wheel angle and the size of the airbag. It was found that when the standard 20 degrees angle steering wheel was used, neck joint torques were decreased by 22 percent while the resultant head acceleration increased 41 percent from the base line study. When the vertical dimension of the airbag was reduced by 10 percent, neck joint torques were increased by 14 percent, while head acceleration showed a slight decrease of 9 percent. PMID- 1522727 TI - Mechanical properties of the rabbit patellar tendon. AB - The mechanical and structural properties of the patellar tendon fascicle-bone units of rabbit knees were determined by tensile tests, particularly focusing on their local differences. There were no significant differences in the strains measured by a video dimension analyzer among the proximal, middle, and distal regions of the central portion of tendon. The mechanical properties of the medial portion agreed well with those of the central portion. However, significant differences were observed in the tensile strength between the lateral and the other two portions: the tensile strength of the lateral portion was about 16 percent larger than those in the other portions. PMID- 1522728 TI - A force-indentation relationship for gymnastic mats. AB - The mechanical properties of a series of gymnastic surfaces are investigated. A Force--Indentation relationship is obtained for each surface. This law can be used to simulate the ground reaction force during under-foot impact with a gymnastic surface. The law is independent of many of the properties of the striking body and when incorporated into a system of differential equations describing the motion of the impacting body, can be used to compute system responses and to investigate the importance of different properties of the various surfaces. Several examples, using both a single, rigid mass and a four link, articulated system are presented, and demonstrate that the relationship can be satisfactorily incorporated into a solution algorithm for a large-displacement dynamical analysis. PMID- 1522729 TI - A parametric study of the thoracic injury potential of basic taekwondo kicks. AB - A parametric investigation of the thoracic injury potential of basic taekwondo kicks was conducted through the use of computer simulations. Linkage-based models were employed to simulate the kinetics of the kicking leg and were used to drive a human thorax model. The results of the analysis according to the thoracic compression criterion indicated a minimal probability of severe injury (AIS4+) for swing kicks, nearly 0 percent and thrust kicks, less than three percent. The thoracic viscous criteria, on the other hand, predicted a severe injury probability of up to 100 percent for swing kicks and up to 80 percent for thrust kicks. Additional analysis showed that the injury potential was a strong function of the kick velocity and a weak function of the applied constant force. The injury potential was also found to be a weak function of the size and weight of the kicking leg, with variations in the peak compression and viscous response being typically below 5 percent for a 20 percent change in either the mass or the length. PMID- 1522730 TI - Contact stress gradient detection limits of Pressensor film. AB - Fuji Pressensor film has been widely used for measurement of contact stresses in articular joints. In relatively smooth contact fields, measurement errors are reported to be in the range of approximately 10-15 percent. However, when local incongruities exist, strong contact stress gradients are present. This study investigates the film's capability to accurately transduce such gradients. Standardized stress distributions were produced by compressing the film between a rigid cylinder and an elastic layer supported by a rigid substrate. Seven different cylinder radii were used to obtain a range of gradient magnitudes. The resulting stains were digitized, and the contact stress gradients assessed by image analysis. Experimentally detected gradients were compared with those predicted analytically. The film's capability to reliably transduce contact stress gradients was shown to be sufficient for usage in the study of typical local articular incongruities. PMID- 1522731 TI - Boundary element method analysis for the bioheat transfer equation. AB - In this paper, the boundary element method (BEM) approach is applied to solve the Pennes (1948) bioheat equation. The objective is to develop the BEM formulation and demonstrate its feasibility. The basic BEM formulations for the transient and steady-state cases are first presented. To demonstrate the usefulness of the BEM approach, numerical solutions for 2-D steady-state problems are obtained and compared to analytical solutions. Further, the BEM formulation is applied to model a conjugate problem for an artery imbedded in a perfused heated tissue. Analytical solution is possible when the conduction in the x-direction is negligible. The BEM and analytical results have very good agreement. PMID- 1522732 TI - A three-dimensional variable geometry countercurrent model for whole limb heat transfer. AB - A new formulation of the combined macro and microvascular model for heat transfer in a human arm developed in Song et al. [1] is proposed using a recently developed approximate theory for the heat exchange between countercurrent vessels embedded in a tissue cylinder with surface convection [2]. The latter theory is generalized herein to treat an arm with an arbitrary variation in cross-sectional area and continuous bleed off from the axial vessels to the muscle and cutaneous tissue. The local microvascular temperature field is described by a "hybrid" model which applies the Weinbaum-Jiji [3] and Pennes [4] equations in the peripheral and deeper tissue layers, respectively. To obtain reliable end conditions at the wrist and other model input parameters, a plethysmograph calorimeter has been used to measure the blood flow distribution between the arm and hand circulations, and hand heat loss. The predictions of the model show good agreement with measurements for the axial surface temperature distribution in the arm and confirm the minimum in the axial temperature variation first observed by Pennes [4] for an arm in a warm environment. PMID- 1522733 TI - Strain fields on cell stressing devices employing clamped circular elastic diaphragms as substrates. AB - Solutions are presented for the surface strain fields on inflated elastomeric circular diaphragms used for in vitro cell stressing experiments. It is shown, by using the method developed by Way (1934) to solve the nonlinear von Karman plate equations, that the surface strains due to bending are not negligible and that large negative radial strains arise near the clamped edge for center deflection to-thickness ratios (w/h) less than 10. The method of Hart-Smith and Crisp (1967) was used for w/h greater than 10 to solve the nonlinear equations for symmetrical deformation of axially symmetrical rubber-like membranes. In the membrane solutions the circumferential strains drop parabolically to zero at the clamped edge of the diaphragm, while the radial strains increase slightly with the radius. The solutions for w/h greater than 10 are compared to optical measurements of in-plane displacements used to calculate the circumferential strains on the diaphragm, yielding excellent agreement with the theory. PMID- 1522734 TI - A numerical study of the shape of the surface separating flow into branches in microvascular bifurcations. AB - The shape of the separating surface formed by the streamlines entering the branches of microvascular bifurcations plays a major role in determining the distribution of red blood cells and other blood constituents downstream from the bifurcation. Using the finite element method, we determined the shape of the surface through numerical solution of three dimensional Navier-Stokes equations for fluid flow at low Reynolds numbers in a T-type bifurcation of circular tubes. Calculations were done for a wide range of daughter branch to parent vessel diameter ratios and flow ratios. The effect of Reynolds number was also studied. Our numerical results are in good agreement with previously reported experimental data of Rong and Carr (Microvascular Research, Vol. 39, pp. 186-202, 1990). The numerical results of this study will be used to predict the concentration of blood constituents downstream from microvascular bifurcations providing that the inlet concentration profile is known. PMID- 1522735 TI - Shear stability of an elastomeric disk spacer within an intervertebral joint: a parametric study. AB - A parametric study was conducted to compare the resistance to shear force provided by three surgical implantation techniques and three endplate designs for use with a polymeric lumbar intervertebral disk spacer. While under an axial load, the implant was pushed out laterally through the surgical window created for implantation. Force at 0.3 mm displacement, slope of the initial portion of the force-displacement graph, and maximum force were measured. The results indicate that implants with pegs, inclined planes, or domes on the surfaces of the disk will add significantly to the shear stability of the implant while maintaining the simplicity of a single part device. PMID- 1522736 TI - Pressure drops through arterial stenosis models in steady flow condition. AB - Measures of pressure drops were made in two different plexiglass models of axial symmetric arterial stenoses. The stenosis models had the same area reduction (86 percent) but were of different length so as to have a different tapering degree. Pressures were measured in steady flow condition at three equidistant points of the stenosis: upstream, in the middle, and downstream. Results indicate that: the upstream-middle pressure drop is independent of tapering degree but is highly influenced by area reduction; moreover it is much greater than the middle downstream drop. The upstream-middle pressure drop can be accurately predicted by means of a relationship deduced by the momentum equation. PMID- 1522737 TI - Pretension critically affects the incremental strain field on pressure-loaded cell substrate membranes. PMID- 1522738 TI - Adaptative control of above knee electro-hydraulic prosthesis. AB - Conventional designs of an above-knee prosthesis are based on mechanisms with mechanical properties (such as friction, spring and damping coefficients) that remain constant during changing cadence. These designs are unable to replace natural legs due to the lack of active knee joint control. Since the nonlinear and time-varying dynamic coupling between the thigh and the prosthetic limb is high during swing phase, an adaptive control is employed to control the knee joint motion. Two dimensional simulation indicates that the adaptive controller can improve the appearance of gait pattern. It is adaptable to walking speed and can compensate for the variations of hip moment, hip trajectory and toe-off conditions. PMID- 1522739 TI - Lung transplantation. AB - Advances in solid organ transplantation over the last several decades have made human lung transplantation a realistic possibility for selected patients with end stage lung disease. A review of clinical indications, proper patient selection, and long-term management is presented. Infection and rejection continue to represent 2 major areas of posttransplantation complications and merit particular attention. PMID- 1522740 TI - Influence of azelastine and some selected drugs on mucociliary clearance. AB - The effect of azelastine and some selected compounds on ciliary beating frequency (CBF) was investigated in vitro using human mucosal samples and in vivo using anesthetized guinea pigs. Further influence of azelastine on mucus secretion was evaluated in mice and on mucociliary clearance in anesthetized rabbits. Azelastine influenced the ciliary beating frequency neither in vitro nor in vivo. Azelastine, similarly to salbutamol, ambroxol, and bromhexine, increased mucus secretion measured by the tracheal output of phenol red. Azelastine dose dependently enhanced mucociliary clearance measured by elimination of 99mTc labeled erythrocytes in rabbits. The activity of azelastine proved to be about 10 times stronger than that of bromhexine. Since the ciliary activity remained unchanged under the influence of azelastine, it is likely that azelastine increases the mucociliary clearance by enhancing bronchial secretion. It is possible that the observed increase in mucociliary clearance may contribute to the beneficial effect of azelastine in the treatment of respiratory diseases. PMID- 1522741 TI - Hyaluronan (hyaluronic acid) in lung lavage of asbestos-exposed humans and sheep. AB - The concentration of hyaluronan was measured in the bronchoalveolar lavage fluid (BALF) of 18 control subjects and 27 workers from the asbestos mills and mines of Quebec, 9 without asbestosis and 18 with asbestosis. Hyaluronan was also measured in the BALF of 9 control sheep exposed to 100 ml phosphate-buffered saline (PBS) at 10 day intervals for 39 months, and 13 sheep exposed at the same intervals to 100 mg chrysotile in 100 ml PBS for 24 months. At month 24, the asbestos-exposed sheep were classified into 3 groups: (A) 4 sheep exposed to PBS alone, (B) 4 sheep exposed to 10 mg chrysotile asbestos every 10 days, and (C) 5 sheep exposed to 100 mg chrysotile asbestos every 10 days for 15 months. The BALF hyaluronan averaged 53.9 +/- 7.4 ng/ml in human controls, 67.5 +/- 10.3 ng/ml in asbestos exposed workers without asbestosis, and 206 +/- 83 ng/ml in workers with asbestosis (p less than 0.05 vs. normal). In the control sheep, BALF hyaluronan was 34.7 +/- 6.9 ng/ml, and it was 31.5 +/- 17.8 ng/ml in the low-dosage asbestos exposed group (A), 83.0 +/- 27.7 ng/ml in the intermediate-dose group (B), and 248.0 +/- 134.7 ng/ml in the high-dosage group (C) (p less than 0.05 vs. controls). In contrast, the release of plasminogen activator, a protease that may play a role in limiting the fibrotic process, was increased in group A, but not in groups B and C. In conclusion, BALF hyaluronan constitutes an indicator of lung interstitial tissue changes that may reflect the activity of the fibrosing alveolitis associated with chronic asbestos exposure. PMID- 1522742 TI - Later development of asthma in patients with a negative methacholine inhalation challenge examined for suspected asthma. AB - A negative methacholine inhalation challenge (MIC) in a patient with suspected bronchial asthma is generally considered to make this diagnosis unlikely. Nevertheless, the patient may later develop asthma. To estimate the proportion that eventually becomes asthmatic, a 10 year follow-up study was carried out on 334 consecutive MIC-negative patients aged 14-80 years. The development of asthma among these patients was assessed on the basis of entitlement to preferential refund from the cost of antiasthmatic therapy granted for them under national health insurance. During the follow-up 30 patients (9%) were granted the refund. There was no significant difference between men and women in this respect. Patients who developed asthma were somewhat older than those who did not. A family history of allergy, allergic rhinitis, and positive reactions to skin prick tests were significantly more common in patients with future asthma. These patients also had a lower mean forced expiratory volume in 1 sec (FEV1) (% of predicted) and a higher mean increase in PEF after an inhaled sympathomimetic than those remaining free from asthma. In multivariate analyses with a logistic model, 3 risk indicators proved independent predictors of future asthma: age, positive family history of allergy, and FEV1 (% of predicted). PMID- 1522743 TI - K+ channel openers and insulin release. AB - Recent in vivo and in vitro experiments suggested that the smooth muscle relaxation mediated by diverse pharmacologic agents resulted from K+ channel opening. Pinacidil, cromakalim, nicorandil, RP 49356, minoxidil sulfate and diazoxide belong to this new group of smooth muscle relaxants: the "K+ channel openers". Because modifications in the K+ permeability are known to represent a critical event in the insulin-releasing process, numerous studies have been performed in order to examine the putative effects of K+ channel openers on B cell function. The aim of the present review is to summarize these experimental data which are sometimes divergent. PMID- 1522744 TI - Human chorionic gonadotropin causes an estrogen-mediated induction of rat ovarian carbonyl reductase. AB - We earlier reported that human chorionic gonadotropin (hCG) stimulates rat ovarian carbonyl reductase (CR) activity and content, and that estrogen enhances the stimulatory effect. The present study was performed to determine the mode of action of the gonadotropin. Cycloheximide (CHX) and actinomycin D (AD) were given to estradiol-pretreated immature rats 6 h before hCG treatment. The enzyme activity was measured with three substrates, and the enzyme content was determined by the method of Western-blot analysis using anti-rat ovarian CR anti serum as the first antibody. Both protein inhibitors significantly prevented hCG from increasing the enzyme activity and content in estradiol-pretreated ovary. These results indicate that rat ovarian CR is induced by LH via the action of estrogen. PMID- 1522745 TI - Contrasting effects of pituitary adenylate cyclase activating polypeptide (PACAP) on in vivo and in vitro prolactin and growth hormone release in male rats. AB - Pituitary adenylate cyclase activating polypeptide (PACAP) is produced by hypothalamic neurons which terminate within the median eminence suggesting that it may be a hypophysiotropic hormone. However, little endocrine activity has been ascribed to the peptide. Therefore we studied the effects of PACAP on prolactin (Prl) release from dispersed cultivated rat pituitary cells in vitro using conventional cultures as well as the reverse hemolytic plaque assay (RHPA). Furthermore the effects of the peptide on in vitro GH release were assessed. In addition, the activity of the peptide on in vivo release of Prl and GH was studied in hypothalamus-lesioned animals. PACAP dose dependently inhibited Prl release form dispersed pituitary cells in both, monolayer cell cultures and the RHPA, whereas GH secretion was not affected. In hypothalamus-lesioned rats which have high Prl levels due to the absence of hypothalamic dopamine, PACAP further stimulated Prl release. Serum GH increased more than 20 fold in response to the intravenous PACAP infusion. Thus in vitro (inhibition of Prl release, no effect on GH release) and in vivo (stimulation of both hormones) experiments yielded contradicting effects of PACAP on pituitary hormone release. We suggest that PACAP may stimulate the release of a paracrine, yet unknown factor which in the intact pituitary overrides the direct inhibitory action of PACAP on the lactotropes. The same or another paracrine factor may also enhance in vivo GH release. In cell culture the paracrine factor is diluted by the medium. Therefore the peptide never reaches effective concentrations which are present within the intact pituitary tissue. PMID- 1522746 TI - Effects of ketanserin on DOI-, MCPP- and TRH-induced prolactin secretion in estrogen-treated rats. AB - The effects of ketanserin (Ket), a serotonin (5-HT2) receptor antagonist, on DOI- and mCPP-, two 5-HT agonists, and TRH-induced PRL secretion were studied. Adult female Sprague-Dawley rats ovariectomized for two weeks and treated with a long acting estrogen, polyestradiol phosphate for one week were used. Drug administration and serial blood sampling were accomplished through indwelling intraatrial catheters which were implanted two days before the experiment. Both DOI (0.5 mg/kg BW) and mCPP (1 mg/kg BW) stimulated prolactin secretion within 10 min after iv injection and the effects were diminished by 30 min. In animals pretreated with Ket (5 mg/kg BW, sc), the effect of DOI was blocked, while that of mCPP was augmented. Co-administration of Ket (1 mg/kg BW, iv) with DOI or mCPP produced similar effect. Pretreatment with Ket, similar to sulpiride (Sulp), a dopamine antagonist, potentiated the TRH-induced prolactin secretion. Co administration of Ket and Sulp further potentiated the TRH action. It is concluded that Ket not only acts as a 5-HT2 receptor antagonist that blocks the action of DOI, but may also act on dopamine receptor(s) with lower sensitivity to Sulp. PMID- 1522747 TI - Dantrolene stimulates renin secretion by rat renal cortical slices but fails to block calcium-dependent inhibition. AB - Calcium (Ca) is an inhibitory second messenger in renin secretion, and it has been proposed that some first messengers, such as angiotensin II (A-II), antidiuretic hormone (ADH), and N6-cyclohexyladenosine (CHA), increase Ca and thereby inhibit renin secretion by mobilizing Ca from intracellular sequestration sites. The present experiments were designed to test this proposal by using dantrolene, an antagonist of intracellular Ca mobilization. Dantrolene stimulated renin secretion by rat renal cortical slices in a concentration dependent manner; at 0.0, 0.1, and 0.5 mM dantrolene, secretory rates were 8.1 +/- 0.6, 9.4 +/- 0.6 (p less than 0.05), and 14.9 +/- 1.2 (p less than 0.0001) GU/g x hr, respectively. These results could be interpreted to mean that Ca mobilization is occurring at a finite rate during the basal state, and that by antagonizing this process, dantrolene lowers intracellular Ca and thereby stimulates renin secretion. However, 0.1 mM dantrolene failed to antagonize the inhibitory effects on renin secretion of A-II, ADH, and CHA, and only CHA-induced inhibition of renin secretion was antagonized by 0.5 mM dantrolene. We conclude that if A-II, ADH, and CHA inhibit renin secretion by mobilizing Ca from an intracellular storage site, then the site is insensitive to dantrolene. PMID- 1522748 TI - Decreased levels of muscarinic receptors in bladders from the alcohol preferring rat line. AB - The Bmax for [3H]QNB binding in the bladders of alcohol preferring (AA) rats was only approximately 60% of that in the alcohol non-preferring (ANA) rats. No significant change in Bmax for [3H]QNB binding in bladder was observed between alcohol insensitive (AT) and alcohol sensitive (ANT) rats. No significant change in Kd for [3H]QNB binding in bladder was observed between the four different rat lines studied. Therefore, alcohol preference but not sensitivity is associated with a decrease in muscarinic receptor density in the rat bladder. Because all of the rats used in this study were ethanol-naive, the decrease in muscarinic receptor density in the bladders of alcohol preferring rats is associated with genetic factors inherent to this rat line. Further studies are needed to determine if these observations are tissue specific or specific to the m2 subtype, which predominates in the rat bladder. PMID- 1522749 TI - Ibogaine reduces amphetamine-induced locomotor stimulation in C57BL/6By mice, but stimulates locomotor activity in rats. AB - The effect of ibogaine hydrochloride on locomotor stimulation induced by d amphetamine sulfate was tested in male C57BL/6By mice and in female Sprague Dawley rats. In mice, locomotor stimulation induced by d-amphetamine at 1 or 5 mg/kg s.c. was reduced by prior administration of one or two injections of ibogaine (40 mg/kg), given 2 or 18 hours earlier. This reduction in locomotor activity persisted for two days. Locomotor stimulation induced by a higher dose (10 mg/kg) of d-amphetamine was not reduced by such prior administration of ibogaine. A lower dose of ibogaine (20 mg/kg) did not reduce the subsequent locomotor activity induced by d-amphetamine. Ibogaine decreased striatal dopamine levels, while d-amphetamine increased them. Ibogaine treatment (2 x 40 mg/kg, 18 hours apart) induced a decrease by 30% in the level of striatal dopamine and its metabolites measured in tissue extracts 3 hours after the second ibogaine injection. One hour after d-amphetamine (5 mg/kg) administration, the level of striatal dopamine increased by 26%. Although the level of striatal dopamine was initially lower in the ibogaine-pretreated mice, d-amphetamine (5 mg/kg) administration induced an increase in striatal dopamine and its metabolites. The effect of ibogaine seems to be species specific, since in rats pretreated with ibogaine 18 hours before d-amphetamine, locomotor stimulation induced by d amphetamine was further increased. In addition, the in vitro electrical-evoked release of [3H]dopamine from striatal tissue was either unchanged or inhibited in the presence of d-amphetamine, and after ibogaine pretreatment in vivo, the release of tritium in the presence of d-amphetamine was inhibited or stimulated in mice and rats, respectively. PMID- 1522750 TI - The effect of cobrotoxin on cholinergic neurons in the mouse. AB - By using multiple time-point constant-rate infusions of deuterium-labeled phosphorylcholine, appropriate kinetic parameters were obtained for use in the calculation of the turnover rate of acetylcholine (TRACh) in selected mouse brain regions. After obtaining these data, the relationship between the analgesic agent cobrotoxin (CT) and the activity of central cholinergic neurons was investigated by determination of TRACh in selected mouse brain regions 3 hours following intracerebroventricular (i.c.v.) injection of CT. There were no obvious changes in the concentrations of ACh and choline (Ch) in the cortex, hippocampus, hypothalamus, midbrain, striatum, or thalamus of the mouse after injection of an analgesic dose of CT (2 micrograms, i.c.v.). TRACh in the thalamus and the striatum were significantly increased, as compared to controls. On the other hand, i.c.v. injection of CT was found to significantly reduce TRACh in the hippocampus and midbrain. These results suggest that the activity of hippocampal and midbrain cholinergic neurons is suppressed by CT, whereas the activity of striatal and thalamic cholinergic neurons is increased by CT at a time when a maximum analgesic response to CT is expressed. PMID- 1522751 TI - Effect of chronic administration of dexfenfluramine on blood pressure in salt sensitive rats. AB - Chronic administration of dexfenfluramine, at a relatively low daily dose, slowed the development of salt-induced elevation of blood pressure in salt-sensitive (Dahl DS and Rapp SS) rats. This effect could not be accounted for by drug related anorexia alone. Elevated serotonin activity, possibly in the brain, may underlie this antihypertensive action of dexfenfluramine. PMID- 1522752 TI - Inhibition of immunoreactive growth hormone secretion from lymphoid cell lines by dexamethasone. AB - The regulation of irGH secretion by the immune system was examined using lymphoid cell lines, H9 and IM9. Using a highly sensitive immunoassay, irGH secretion by H9 was negatively regulated by dexamethasone, whereas many other regulators of hGH secretion, including hormones, monoamines, and second messenger, had no measurable effect on irGH secretion. Treatment of H9 cells with dexamethasone for 48 hours could cause as high as 70% reduction in irGH secretion without affecting either cell numbers or viability. Using IM9, neither growth hormone releasing hormone nor thyrotropin releasing hormone had significant effect on either irGH steady-state level transcripts or irGH secretion. These findings suggest that irGH secretion by lymphocytes was regulated in a different manner from that by pituitary cells. PMID- 1522753 TI - Stimulation of sulfated glycosaminoglycan synthesis by the tripeptide-copper complex glycyl-L-histidyl-L-lysine-Cu2+. AB - Glycyl-L-histidyl-L-lysine-copper (II) complex (GHK-Cu) is a naturally occurring tripeptide with potential healing properties. We studied the effect of GHK-Cu on the synthesis of glycosaminoglycans (GAGs) by normal human fibroblasts in culture. Cells were incubated with 3H glucosamine and 35S sulfate and the radioactivity of isolated GAGs was determined. GHK-Cu induced a dose-dependent increase of the synthesis of total GAGs secreted into the culture medium and those associated with the cell layer. The effect of GHK-Cu was biphasic with a maximal stimulation at 10(-9) to 10(-8) M. At higher concentrations, the rate of synthesis returned progressively to that of control cultures. Electrophoretic analysis of the different GAG populations showed that GHK-Cu preferentially stimulated the synthesis of extracellular dermatan sulfate and cell layer associated heparan sulfate. No influence of GHK-Cu on the synthesis of hyaluronic acid was observed. GHK-Cu stimulation of GAG synthesis may be one of the phenomenons implicated in the wound healing properties of the peptide. PMID- 1522754 TI - Relationship between hypothalamic noradrenergic activity and the sympathetic activity in interscapular brown adipose tissue after cold-swim stress in rats. AB - Noradrenaline (NA) activities in both hypothalamus and interscapular brown adipose tissue (IBAT) were simultaneously assessed before and after cold-swim stress in rats. The technique of gas chromatography-mass spectrometry was employed for the analysis of NA and its primary neuronal metabolite, 3,4 dehydroxy-phenylethylenglycol (DHPG), and the ratio of DHPG to NA was used as an index of NA activity. The ratios of DHPG/NA in both hypothalamus and IBAT were significantly elevated 5 and 20 min after cold-swim stress. Moreover, we found that there is a highly significant positive relationship between the hypothalamic DHPG/NA ratio and the ratio of DHPG/NA in IBAT (r = 0.872, p less than 0.0001). This observation strongly supports the concept in which hypothalamic NA neurons play an important role in modulating the sympathetic outflow. PMID- 1522755 TI - Studies on the intracellular degradation of newly synthesized collagen in 3 methylcholanthrene induced fibrosarcoma cells. AB - The intracellular degradation of newly synthesized collagen was studied in both normal fibroblast and 3-methylcholanthrene induced fibrosarcoma cells. The degradation of newly synthesized collagen was examined using pulse-chase experiments and radioactive labelling techniques with [3H]-proline. The percentage of intracellular proteolysis of newly synthesized collagen was determined by measuring the formation of [3H]-hydroxyproline containing fragments in alcohol-soluble and insoluble fractions of normal cells and fibrosarcoma cells in the culture. The rate of degradation of newly formed collagen was then followed by estimating the radioactivity of [3H]-hydroxyproline at different intervals, during the chase period. The results clearly demonstrated that the percent of intracellular degradation of newly synthesized collagen was approximately three fold higher in fibrosarcoma cells than in normal fibroblast cells. The increased intracellular degradation of newly formed collagen was followed by an increase in the activity of cathepsin B and L in fibrosarcoma cells. The pulse-chase experiments indicated that the rate of degradation of newly synthesized collagen in fibrosarcoma cells is relatively greater than in normal fibroblast cells. In addition, as the labelling time increased, the formation of [3H]-hydroxyproline containing peptides in the ethanol-soluble fraction were found to be increased in both normal cells and fibrosarcoma cells, but the extent of formation was higher in fibrosarcoma cells compared to normal fibroblast cells. The results of this investigation collectively suggest that the intracellular degradation of newly synthesized collagen is enhanced in fibrosarcoma cells. PMID- 1522756 TI - Effects of adenosinergic drugs on hypoxia-induced electrophysiological changes in rat hippocampal slices. AB - The effects of adenosinergic antagonists caffeine and DPCPX, and of the adenosinergic agonists L-PIA, CPA and CGS 21680 were investigated on fully and partially reversible hypoxia-induced electrophysiological changes in rat hippocampal slices. The influence of a high potassium solution and of the N methyl-D-aspartate antagonist dizocilpine (MK 801) was also tested. The latency to obtain a 50% decrease in the amplitude of the CA1 population spike (CA1 PS) during a short- (5-10 min) lasting hypoxic period was significantly increased (P less than 0.01) by slice perfusion with caffeine (50 microM), DPCPX (0.2 microM), and by increasing (from 3 to 4 mM) the potassium concentration in the medium bathing the hippocampal slices. The latency was significantly decreased (P less than 0.01) by slice perfusion with L-PIA (0.2 microM) and CPA (0.05 microM). It was not significantly modified by CGS 21680 (5 microM). The incidence of reappearance of the CA1 PS during reoxygenation after long- (45 min) lasting hypoxia was significantly increased (P less than 0.05) by slice perfusion with MK 801 (50 microM), while it was not significantly affected by slice perfusion with caffeine (50 microM) or DPCPX (0.2 microM) or L-PIA (0.2 microM) or CPA (0.05 microM) or CGS 21680 (5 microM). The results indicate a prevalent involvement of the A1 adenosine receptors in the early mechanisms underlying hypoxia-induced reversible changes. Adenosine seems to have a limited role in the late mechanisms occurring after a long-lasting hypoxic period. PMID- 1522757 TI - Effects of prior exposure to cocaine: interaction of reinforcing and suppressant effects. AB - Squirrel monkeys were trained to respond under second-order schedules of food presentation and then sequentially exposed to either a self-administration (SA) and then a conditioned taste aversion (CTA) procedure, or a CTA procedure and then a SA procedure. Initial exposure to stimuli associated with post-session delivery of cocaine (0.3 mg/kg) either maintained (SA) or suppressed (CTA) responding, respectively. In contrast, following exposure to CTA, SA procedures failed to maintain levels of responding comparable to those seen with initial exposure to SA. Following exposure to SA, the CTA procedure failed to suppress responding. Thus, prior exposure to either the reinforcing or suppressant effects of cocaine modified its subsequent behavioral effects, suggesting a unique role for behavioral history in the abuse potential of cocaine. PMID- 1522758 TI - Sexual differences in the activity of periventricular-hypophysial dopaminergic neurons in rats. AB - The activities of periventricular-hypophysial dopaminergic (DA) neurons were compared in male and female rats by measuring dopamine synthesis (accumulation of 3,4-dihydroxyphenylalanine [DOPA] after inhibition of L-aromatic amino acid decarboxylase) and metabolism (concentrations of 3,4-dihydroxyphenylacetic acid [DOPAC]) in terminals of these neurons in the intermediate lobe of the pituitary. For comparison, the synthesis and metabolism of dopamine in the neural lobe of the pituitary and median eminence were also determined. The concentrations of DOPAC and accumulation of DOPA were higher in females than in males in both the intermediate lobe and median eminence, revealing a sexual difference in the basal activity of periventricular-hypophysial and tuberoinfundibular DA neurons. In contrast, there were no differences between male and female rats in activity of DA neurons terminating in the neural lobe. One week following gonadectomy, DOPA accumulation in the median eminence was decreased in females and increased in males, but remained unchanged in the intermediate lobe. These results indicate that sexual differences in the activity of periventricular-hypophysial DA neurons terminating in the intermediate lobe are not dependent upon the presence of circulating gonadal steroids, and in this respect, these neurons differ from tuberoinfundibular DA neurons. PMID- 1522759 TI - Effects of n-3 and n-6 fatty acids on tumor necrosis factor cytotoxicity in WEHI fibrosarcoma cells. AB - Modulation by fatty acids of the cytotoxic effect of recombinant tumor necrosis factor alpha (TNF) toward WEHI 164 mouse fibrosarcoma cells has been examined. Preincubating the highly TNF-sensitive WEHI clone 13 cells for 44 hr with 50 mumol/L of 20:5n-3, 22:6n-3, 18:3n-6, 20:3n-6 or 20:4n-6 reduced cell survival 22 hr after challenge with TNF (40 ng/L) by 65%, 72%, 60%, 98% and 85%, respectively. In comparison, 18:3n-3, 18:2n-6 and 18:1n-9 had only negligible effects on TNF-induced toxicity. Different extent of fatty acid incorporation into cell total phospholipids or triglycerides could not explain the observed effects on TNF cytotoxicity, and the enhanced cytotoxicity could therefore not be explained merely by an increased unsaturation of the cell membranes. In addition to the fatty acid supplied, preincubation with 18:2n-6, 18:3n-6 or 18:3n-3 also enriched the cells with 20:2n-6, 20:3n-6 and 20:3n-3, respectively, most likely due to chain elongation. The results suggest that the WEHI cells have a low delta 6 desaturase activity, and that n-6 and n-3 acids must have at least 3 or 4 double bonds, respectively, to enhance TNF cytotoxicity in WEHI cells. Dexamethasone partly inhibited TNF-induced cytotoxicity, while cyclooxygenase, thromboxane synthetase or lipoxygenase inhibitors had no or negligible effects. The antioxidant butylated hydroxyanisole (BHA) completely inhibited TNF-induced cytotoxicity, while the structurally and functionally similar antioxidant butylated hydroxytoluene had no such effect, indicating that BHA does not block TNF cytotoxicity through its antioxidant effect.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1522760 TI - The effect of dietary supplementation with eicosapentaenoic acid on the phospholipid and fatty acid composition of erythrocytes of marmoset. AB - Adult male marmoset monkeys were fed eicosapentaenoic acid (20:5n-3) as the ethyl ester in diets containing either 32% (reference diet, no added cholesterol) or 7% (atherogenic diet with 0.2% added cholesterol) linoleic acid (18:2n-6) for 30 wk. No changes were seen in the level of phosphatidylcholine (PC) or phosphatidylethanolamine (PE) but minor changes were observed in both the sphingomyelin (SPM) and phosphatidylinositol plus phosphatidylserine (PI+PS) fractions of erythrocyte lipids. The extent of total n-3 fatty acid incorporation into membrane lipids was higher in atherogenic diets (polyunsaturated/monounsaturated/saturated (P/M/S) ratio 0.2:0.6:1.0) than reference diets (P/M/S ratio 1:1:1) and this was true for both PE (33.4 +/- 1.0% vs 24.3 +/- 1.1%) and PC (9.3 +/- 0.5% vs 4.9 +/- 0.3%). Although suitable controls for cholesterol effects were not included in the study, earlier results obtained with marmosets lead us to believe such effects were probably small. Regardless of basic diet (atherogenic, reference), 20:5n-3 was preferentially incorporated into PE (10.8 +/- 0.2%, 6.0 +/- 0.02%) while smaller amounts were incorporated into PC (6.9 +/- 0.4%, 3.2 +/- 0.2%). The major n-3 polyunsaturated fatty acid found in PE in response to dietary 20:5n-3 was the elongation metabolite 22:5n-3 in both the atherogenic (17.7 +/- 0.7%) and reference (14.3 +/ 1.0%) dietary groups; 22:6n-3 levels were less affected by diet (4.7 +/- 0.3% and 3.9 +/- 0.2%, respectively).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1522761 TI - Monoenoic fatty acids in human brain lipids: isomer identification and distribution. AB - The carbon chain length distribution and the double bond positional isomer composition of the monoenoic fatty acids of the lipids of total human brain tissue have been determined using gas chromatography and gas chromatography/mass spectrometry of the fatty acid methyl and picolinyl esters. The even chain length monoenoic C16 to C28 fatty acids contain predominantly two positional isomer series, the n-7 and n-9 cis homologues, whose relative proportion varies significantly with chain length. The odd chain length long-chain fatty acids consist of n-8 and n-10 isomers, whereas the odd chain length very long-chain (more than 22 carbon) fatty acids are n-7 and n-9 isomers. PMID- 1522762 TI - Effects of polyphenolic natural products on the lipid profiles of rats fed high fat diets. AB - Male Wistar rats were fed a high fat diet (HFD) containing 2.5% cholesterol and 16% lard supplemented with polyphenolic natural products namely quercetin, morin or tannic acid (100 mg/rat/day) for 4, 7 and 10 wk. Rats fed HFD without the supplements served as control. The effects of these compounds on blood lipid profiles, enzymes, liver fat and aorta of the rat were studied. In rats fed HFD containing tannic acid, plasma total cholesterol (TC), low density lipoprotein cholesterol (LDLC) and triglyceride (TG) were reduced by 33.3%, 29.6% and 65.1%, respectively, at week 10. High density lipoprotein cholesterol (HDLC) concentration was not altered. Fat deposition was also decreased in the liver of these rats. Morin significantly reduced plasma TG (65.1%) and liver fat only at week 7 while at week 10 it reduced plasma TC and LDLC by 30.9% and 29.3% respectively. The plasma HDLC concentration was increased by 47.3% at week 4 but no effect was seen at weeks 7 and 10. In the rats fed HFD containing quercetin, plasma HDLC was increased by 28.6% at week 7 but at week 10, plasma LDLC was increased by 21.2%. Quercetin did not cause any significant changes on the plasma TC, TG and liver fat at weeks 4, 7 and 10. Plasma alanine aminotransferase, alkaline phosphatase and bilirubin in control and treated groups were not significantly different. However, hepatic lipase activity in rats fed tannic acid was significantly lower. Aortae of all groups of rats showed no abnormalities. The present report indicates that tannic acid and morin are effective in reducing plasma and liver lipids when supplemented with a high fat diet in rats. PMID- 1522763 TI - Subterminal hydroxylation of lauric acid by microsomes from a marine fish. AB - Microsomes from the liver of sea bass (Dicentrarchus labrax) were shown to hydroxylate lauric acid at subterminal positions. The cytochrome P-450 system converted lauric acid to several mono-hydroxylated metabolites including omega-1 hydroxylaurate, which was the major metabolite (44% of total products). In addition, omega-2, omega-3, omega-4 and a small amount (2.3%) of omega hydroxylaurates were found. Reaction products were identified using thin-layer chromatography (TLC) and gas chromatography/mass spectrometry (GC/MS). Oxidation reactions were dependent upon O2 and NADPH, and did not occur with boiled microsomes or in the presence of a mixture of CO/O2. Hydroxylation proceeded linearly up to 20 min at 28 degrees C for protein concentrations below 380 micrograms. Treatment of fish with benzo(a)pyrene (BP) (20 mg/kg) drastically increased xenobiotic metabolism (ECOD, EROD and BPMO activities), but no difference in laurate hydroxylase activity was observed between untreated and treated fish. Starvation strongly enhanced laurate hydroxylase activity, and resumption of feeding reduced by half this increase of activity. In all of the experiments we did not observe any modification of the regioselectivity of lauric acid hydroxylation by this microsomal in-chain hydroxylating system. We suggest that cytochrome P-450 enzymes involved in lauric acid and xenobiotics metabolism are regulated independently. PMID- 1522764 TI - Inhibition of ferrous-induced lipid peroxidation by pyrimido-pyrimidine derivatives in human liver membranes. AB - The effects of pyrimido-pyrimidine derivatives (dipyridamole, RA-642, and RA-233) on lipid peroxidation, using d-alpha-tocopherol as standard, were studied in enriched membrane fractions from human and rat hepatocytes. Equimolar concentrations of ferrous sulfate and ascorbic acid were used to induce lipid peroxidation. The amount of peroxidized lipids observed in membrane fractions from human liver was smaller than in those from rat liver. In both species, however, pyrimido-pyrimidine derivatives, except for RA-233 in rat liver, inhibited lipid peroxidation dose-dependently in the following sequence: RA-642 greater than dipyridamole greater than d-alpha-tocopherol RA-233. PMID- 1522765 TI - A sensitive and specific radioimmunoassay for platelet-activating factor. AB - A platelet-activating factor (PAF) analog with a reactive omega-aldehyde group at the sn-1 position was synthesized. The hapten-thyroglobulin conjugate was used to immunize rabbits to produce specific antibodies to PAF. The purified immunoglobulin G (IgG) fraction was found to bind stereo-specifically to tritiated PAF and to crossreact minimally with lysoPAF, plasmalogens, and other phospholipids. The radioimmunoassay detected as little as 20 pg of PAF per assay tube and was used to explore agonist-induced synthesis of PAF in rabbit neutrophils. Calcium ionophore A23187 at 1 microM induced PAF synthesis peaking at 2 min and reaching basal levels after 5 min. N-Formyl-Met-Leu-Phe (FMLP) at 0.1 microM also stimulated rapid synthesis and degradation of PAF with a peak at 5 min. Both A23187 and FMLP stimulated PAF synthesis in a dose-dependent manner. The radioimmunoassay should be applicable to the quantitation of PAF in biological samples. PMID- 1522767 TI - The inhibitory effect of water on the Co2+ and Cu2+ catalyzed decomposition of methyl linoleate hydroperoxides. AB - The inhibitory effect of water on the decomposition of methyl linoleate hydroperoxides (MLHP) catalyzed by Co2+ and Cu2+ was studied in a model system using proton nuclear magnetic resonance (NMR) spectroscopy. MLHP were prepared by photoxidation and purified by chromatographic methods. Proton NMR spectroscopy was used to measure reaction rates by monitoring changes in the intensity of the OOH signal. The rate constant of the reaction was obtained by plotting the natural logarithm of MLHP concentration vs time. In the first part of the study, no transition metals were added to the model system, so that the effect of water could be attributed to the interaction between water and MLHP only. The rate constant of the reaction (K) was found inversely proportional to the concentration of water. There was a downfield chemical shift of both hydroperoxide and water peaks in the NMR spectra when water was added. As temperature increased to 40 degrees C, the difference in K between the systems with 0% and 2% water disappeared. It is proposed that the hydroperoxides were solvated with water which retarded their decomposition. When Co2+ was added to the model system, K decreased as the concentration of water increased from 0% to 1.5%. As temperature increased from 18 degrees C to 40 degrees C, differences between the K for 0% and 2% water disappeared. A similar phenomenon was observed in reactions catalyzed with Cu2+. These findings would support a mechanism in which the protective effect of water involves both the solvation of OOH and hydration of the metal catalyst. PMID- 1522768 TI - Bio-clinical prevalence or non-prevalence of drug addiction over psychiatric symptomatology. AB - It has been found that opiate abusers once detoxified are afflicted with personality disorders. An attempt was made to test the origin of drug abuse by comparing a group of drug abusers with personality disorders diagnosed as borderline or schizotypal with a group of people suffering from similar personality disorders but who did not use drugs. The results of the test are discussed. PMID- 1522766 TI - Metals and lipid oxidation. Contemporary issues. AB - Lipid oxidation is now recognized to be a critically important reaction in physiological and toxicological processes as well as in food products. This provides compelling reasons to understand what causes lipid oxidation in order to be able to prevent or control the reactions. Redox-active metals are major factors catalyzing lipid oxidation in biological systems. Classical mechanisms of direct electron transfer to double bonds by higher valence metals and of reduction of hydroperoxides by lower valence metals do not always account for patterns of metal catalysis of lipid oxidation in multiphasic or compartmentalized biological systems. To explain why oxidation kinetics, mechanisms, and products in molecular environments which are both chemically and physically complex often do not follow classical patterns predicted by model system studies, increased consideration must be given to five contemporary issues regarding metal catalysis of lipid oxidation: hypervalent non-heme iron or iron oxygen complexes, heme catalysis mechanism(s), compartmentalization of reactions and lipid phase reactions of metals, effects of metals on product mixes, and factors affecting the mode of metal catalytic action. PMID- 1522769 TI - Cyanide dermatosis or a post-mortem artefact?--A case report. AB - A case of a chronic alcoholic, found dead in the afternoon after consuming an intoxicant early in the morning and showing post-mortem skin slippage with a blackened charred-like appearance, is reported. Viscera chemical analysis gave a positive test for significant quantities of cyanide. However, on histopathological examination, since no evidence of blister formation or vital reaction in the skin tissues were found, this was thought to be a very short duration, accelerated postmortem change phenomenon, due to local heating from contact with the sun-baked terrace. PMID- 1522770 TI - Confidentiality in clinical psychiatry. AB - A brief history of the central role of confidentiality in the doctor-patient relationship is presented. Emphasis is placed on the positions of the American Medical Association and World Medical Association. The dilemma posed by the requirement of balancing the rights of the patient against those of society is portrayed. Particular attention is paid to the role of technology and mass society in exacerbating this tension, and the differences between the rights of confidentiality and those of privilege are offered. Recent court cases are cited to illustrate five legal theories to which a patient can resort in alleging damages for the inappropriate disclosure of confidences, as are others in an effort to show the directions in which American courts are heading. Several suggestions are offered to the clinician in dealing with confidentiality. PMID- 1522771 TI - Is a diagnosis of occupational post-traumatic schizophrenia possible? AB - We present the case of a man who became ill with schizophrenia at the age of 44 after he had been subjected to a series of investigations at his place of work. This case illustrates the issue of the development of schizophrenia as a result of trauma or stress. In our presentation we go into a detailed history of the case and the relevant legal and medical aspects, referring to the legal theory of microtrauma and the theory behind stress-vulnerability, in an attempt to contribute to the understanding of schizophrenia. We consider the legal definitions of 'occupational damage' and the 'common illness'. As to qualifying medical terms, medical science looks upon illnesses as resulting from the reciprocity between the organism and the environment. While the organism forever tends to maintain its equilibrium, environmental factors threaten to upset it. Considering mental illnesses in general and schizophrenia in particular, we discuss the theory of 'stress-vulnerability hypothesis'. We convey our opinion on how it is possible to bridge the gap between the law and medical science. Bringing together the two disciplines and their terms is not simple. The most significant question is whether vulnerability, or to be more precise, vulnerability or a genetic tendency, constitutes a natural morbidity process which is aggravated by the traumatic factor, or whether an individual who bears a 'vulnerability' is healthy until he comes into contact with the environmental factor. It is our opinion that one must not attach too much importance to this theory and must not consider it as fact, but rather confine one's judgment to cases where a latent 'vulnerability' has a clear-cut clinical expression. If we rely on a prevalent medical theory as if it were an evident reality we may miss the truth and may attach too much importance to a matter which is as yet solely theoretical. Our aim is to do justice to human beings. It is better to rely on facts than to trust the existence of latent factors which are within the bounds of theory. We also present a review of the literature about the connection between schizophrenia and trauma or unusual events of life. PMID- 1522772 TI - Issues in the classification of mental illnesses within changing social relations. AB - The purpose of this article is to highlight critical issues in the onset and development of mental illnesses. Its contents critically examine the relevance of the standard psychiatric diagnostic measure (the biomedically based DSM III-R) in the classification of mental illnesses within changing social relations characteristic of the South African situation. Reference has been made to case studies whose clinical symptomatology reflects the multifaceted nature of psychological disturbance as it is manifested by people in a transitional state. Its major contribution is the proposition of a phenomenologically based dimensional approach in the conceptualization of the meaning of psychopathology as it is experienced by people in their total social context. PMID- 1522773 TI - Don't say that word! PMID- 1522774 TI - Bodily intrusion, drug search in the human body, human rights and the balance of interests. AB - This article deals with the thorny issue of official authority to search for drugs in the bodies of suspected drug offenders. Relevant Israeli cases and legislation are discussed and a draft bill proposed. PMID- 1522775 TI - The relationship between the perception of alcohol and drug harmfulness and alcohol consumption by university students. AB - University students find themselves at a stage when many attitudes and habits undergo change and consolidation, and it is during this period when patterns of consumption of toxic substances are partially or definitively established. A group of 955 university students (328 medical students, 347 students of veterinary medicine, and 280 law students) were studied. Sex and religion played a decisive role in determining the relation between the use of toxic substances and the subjects' attitude toward consumption in our sample. Also, the three campuses were found to differ significantly with regard to students' assessment of harmfulness and patterns of consumption. PMID- 1522776 TI - Drug rechallenge and patients' rights. AB - Challenging a hypersensitive patient with a potentially harmful drug is most important to the development of medical knowledge. However, it does not always serve the interest of the particular patient. In order to protect the interest of an individual patient, one must abstain from challenge unless it is vital to the health of the particular patient at the time and has no substitute. Patients' rights demand the establishment of limitations and guidelines for the procedure of rechallenge in all its aspects. An approach which will bring physicians closer to a solution, which will protect the patient from uncontrolled decisions and from unnecessary risks, is suggested. PMID- 1522777 TI - New realities and old classifications: a problem in medical ethics. AB - Advances in research and technology are forcing us to confront hitherto unknown forms of life on both macroscopic and microscopic levels. Genetically engineered cells, human embryos growing in Petri dishes or preserved in freezers, human beings without hearts or functioning brains, these are just a few examples of the new forms of life. The challenge now is to determine what actions relative to these unfamiliar realities are morally acceptable. PMID- 1522778 TI - A controlled auction market is a practical solution to the shortage of transplantable organs. AB - All attempts relying on pure altruism to meet the demand for transplantable donor organs have failed and continue to fail. The incentive of commercialization of an organ market would seem to be the only practical solution at this time. It is almost impossible to set fixed prices for such priceless items as human organs. The only fair, honest, and feasible approach is the establishment of a free and voluntary national or international auction system under the strict supervision and control of an exclusive, specially created administrative entity free of governmental or other partisan interference. The resultant flow of funds could be enormous and would enhance the welfare of all strata of society. Wealthy buyers would be removed from current waiting lists; the donor pool greatly expanded to perhaps surplus; the resultant money used to relieve the financial burdens on families involved, hospitals, insurance companies--and also used to buy organs for the indigent on waiting lists, pay for surgeries and hospitalization, and thereby increase the income and surgical experience of more surgeons. This proposed new system should include all live as well as brain-dead donors, cadavers and consenting individuals facing purposeful and pointless destruction by judicial execution. PMID- 1522779 TI - Patients' complaints: some aspects of the evaluation of physicians' conduct by the Danish National Board of Health. AB - This study comprises all complaints made by patients to the Danish National Board of Health in 1984-1985. All disciplinary cases regarding physicians' conduct are evaluated by the board. A quantitative evaluation was carried out of the 1,062 complaints received by the board in the period under study. Special attention was given to some topics. It is emphasized that adverse outcome termed fortuitous has been narrowed over time, but more investigation is needed, in order to have a more objective foundation from which to determine whether an adverse outcome really is fortuitous or whether it is due to negligence. A central registration of cases of adverse outcome is suggested. The problem of allocating responsibility is very much open to debate, but more adequate case journal keeping is also mentioned. It was surprising that violations of information and consent requirements are often sanctioned very mildly, and more attention to this sphere is appropriate in order to ensure patients' rights. In this connection regular inquiries into patient satisfaction should be considered as a feedback mechanism. PMID- 1522780 TI - Informed consent and 'wrongful birth': the Austrian Supreme Court's approach. AB - This article examines to what extent the Austrian Supreme Court is willing to apply the theory of informed consent and wrongful birth. In the decision at issue the judges came to the conclusion that a physician need not inform about every single risk of medical therapy. With regard to wrongful birth, the court left open for further discussion whether maintenance costs which were caused by a physician's negligent conduct are a matter of compensation. PMID- 1522781 TI - IVF in the USA, who pays for it? AB - A decade has passed since the first American 'test-tube baby' was born at the Eastern Virginia Medical School in Norfolk. The announcement of this medical achievement was an excellent source of inspiration for many legal scholars to write about the problems of IVF. The Spanish, English and Swedish legislators were the first to be seduced by these scholars. They enacted very sophisticated statutes concerning fertilization and embryology. The American legislation did not seem (at first sight) to fall under the spell of lawyers. In this article, it is shown how more and more American state legislators, by enacting statutes to mandate insurers to cover IVF treatment, are indirectly regulating IVF. PMID- 1522782 TI - A proposal to require attorney disclosure when a client communicates intent to harm. AB - The attorney-client privilege has been and will remain sacred. But a human life is more sacred. When a life is threatened, and the attorney has knowledge of this danger, he also has an obligation to protect the potential victim. If reasonable care under the circumstances requires him to disclose certain confidences, then an exception to the rule of privilege must be made. DR 4-101 (c)(3) should be changed to reflect this obligation. PMID- 1522783 TI - Medical malpractice: tortious liability or no-fault insurance? AB - This article discusses the merits of no-fault insurance as compared to tortious liability in medical malpractice cases. The implications of adopting the Swedish model in Israel are considered. PMID- 1522784 TI - Images of law and disorder: a survey of forensic mental health professionals in Ontario, Canada. AB - In this article we report on a survey that was organized to expand knowledge across a range of medicolegal issues and pragmatic applications. We wanted to provide forensic professionals with an opportunity to express their views on these various forensic trends, and on their relevance for expert identities, statuses and activities across a broad spectrum of contexts and concerns. In an exploratory framework, the intention was to operationalize many of these developments in systems, laws, ideas and practices, and to present them as structured questions for the consideration of respondents representing the full complement of mental health disciplines connected to the criminal court apparatus in one Canadian province. In what follows we set out to sketch their images of law and disorder, and their specific opinions about the role of forensic practitioners, the nature of forensic assessment and decision-making, the relationship between mental disorder and crime, the application of treatment and punishment, and the overall process of criminal court adjudication and sentencing. PMID- 1522785 TI - The academy movement. A history of the origin of the American Academy of Psychoanalysis. PMID- 1522786 TI - Barriers to clinical computing: what physicians can do. PMID- 1522788 TI - The doc and the dough. PMID- 1522787 TI - Medical practice and statistical analysis. PMID- 1522789 TI - Catch-22 in the era of peer review organizations. PMID- 1522790 TI - Artifacts. PMID- 1522791 TI - Designing a hospital information system: a comparison of interfaced and integrated systems. PMID- 1522792 TI - Effects of computer reminders for influenza vaccination on morbidity during influenza epidemics. AB - To study the effects of computer-generated reminders for influenza vaccination of patients at high risk of pulmonary disease during the winter, we selected 4555 such patients from a population of 15,000 adults who participated in a three-year randomized trial of preventive-care reminders. The physicians who received the reminders vaccinated eligible patients twice as often as did the control physicians (P = 0.0001). There was a linear increase in the incidence of influenza in our area during the three winters under study (from 1000 to 33,451 to 71,075 cases per year), and we modeled the percentage of patients with hospitalizations, emergency room visits with chest radiography, and blood gas determinations as a logistic function of this increase. The difference in linear trends between the patients in the intervention group (whose physicians received reminders) and those in the control group was significant for emergency room visits (P less than 0.05), hospitalizations (P less than 0.01), and blood gas determinations (P less than 0.001). The most likely explanation for the difference is the greater use of influenza vaccine in the intervention group. PMID- 1522793 TI - On exorcizing the ghost of Gauss and the curse of Kelvin. PMID- 1522794 TI - Statistical packages for the Macintosh. AB - These programs represent the entry of the Mac into major statistical computing. We believe that for the physician researcher who is not a statistician, they make the Mac the platform for data analysis. We found that statistics, research design, and data analysis seemed different and much less intimidating to us and our trainees when approached through the Mac. We have reviewed the versions of these programs available at the time of this writing, in May 1992; potential buyers should contact the software publisher for information about more recent upgrades. At this point, our recommendations would be as follows: If you are wedded to SPSS or Minitab, try the Mac versions, and you will be impressed. Otherwise, the choice is between SYSTAT, which has been around long enough to demonstrate its richness and capacity to build on its strengths, and JMP, a brash newcomer, which demonstrates that you can teach an old dog (SAS) new tricks. StatView and SuperANOVA, while endowed with intuitive, easy-to-use interfaces, lack online help--a feature we consider important in a statistics package. We anticipate that the future will lead to simplification of the SYSTAT interface and the addition of more analytic capacities to JMP--and who knows what the next generation of competitors will bring? PMID- 1522795 TI - The limited role of the human interferon system response to respiratory syncytial virus challenge: analysis and comparison to influenza virus challenge. AB - The respiratory syncytial virus (RSV)-induced production of interferon (IFN) by human macrophages and mononuclear leukocytes (MNL) and the sensitivities of RSV to subtypes of IFN-alpha were examined and compared to IFN production induced by influenza virus. Influenza virus induced high titers of total IFN bioactivity, transcription of the IFN-alpha 1 and IFN-beta gene products and production of IFN gamma. In contrast, RSV induced minimal or no detectable total IFN activity, and the absence of IFN bioactivity could not be attributed to inhibitors of IFN activity. There was no detectable transcription of IFN-alpha or IFN-beta gene products by the cells exposed to RSV. RSV-exposed MNL did produce small amounts of IFN-gamma, consistent with prior sensitization of the cell donors to the virus, but titers were substantially lower than those induced by influenza virus. RSV showed minimal but equivalent susceptibility to several subtypes of IFN alpha. The data raise the possibility that the IFN system has a limited direct role in early host defense against RSV infection, but results should not be extrapolated directly to in vivo events. PMID- 1522796 TI - Intranasal infection of infant mice with Neisseria meningitidis. AB - In human meningococcal infection the mechanism of the transition from asymptomatic carriage to invasive disease is unknown, partly due to the lack of an effective animal model that mimics all stages of the human disease. Therefore, we have endeavoured to develop a model for the human infection by instilling a suspension of Neisseria meningitidis into the nostrils of infant mice and subsequently determining the numbers of organisms in the nasal passages, lungs, blood and brains. Intranasal (i.n.) instillation resulted in consistent nasal colonisation which usually developed into a lung infection. In many cases the lung infection preceded bacteraemia, which occasionally resulted in death of the mice. The severity of the infection and the transition to bacteraemia were enhanced by intraperitoneal (i.p.) treatment of the mice with iron dextran or human transferrin. A N. meningitidis strain that was avirulent in an i.p. infection was also avirulent following i.n. infection. The requirement for lung colonisation to precede bacteraemia and the need for i.p. injection of iron compounds limit the use of i.n. infection of the infant mouse as a model for human meningococcal disease. However, various aspects of meningococcal virulence can be examined using this model. PMID- 1522797 TI - A high Mr factor in human blood which confers serum resistance on gonococci: some properties and synergism with CMP-NANA. AB - A high relative molecular mass (M(r)) component which confers serum resistance on gonococci has been purified about 300-fold from a dialysed sonicate of human blood cells. Serum resistance conferred by the high M(r) factor (RIF), like that induced by cytidine-5' monophospho-N acetyl neuraminic acid (CMP-NANA), decreased when gonococci were incubated with neuraminidase. Also, the resistance-inducing activities of both high M(r) RIF and CMP-NANA were inhibited by CMP and inactivated at pH 4.0. These activities were not additive but synergistic. Neuraminidase decreased the activity of high M(r) RIF but not CMP-NANA. In tests with 14C CMP-NANA and gonococcal lipopolysaccharide, no sialyltransferase activity was detected, even in highly active samples of high M(r) RIF under conditions in which low activities of rat liver sialyltransferase were readily detected. Conversely, rat liver sialyltransferase was neither active in the RIF assay nor able to enhance the RIF activity of CMP-NANA. Nevertheless, high M(r) RIF greatly enhanced the sialyltransferase activity of a gonococcal extract; this enhancement suggests an explanation for the synergism between CMP-NANA and high M(r) RIF in inducing serum resistance in gonococci. PMID- 1522798 TI - Epitope analysis of an immunodominant domain on the P1 protein of Haemophilus influenzae type b using synthetic peptides and anti-idiotypic antibodies. AB - Synthetic peptides, anti-idiotypic antibodies (anti-Id) and human and murine monoclonal antibodies (mAbs) were used to further define a major antigenic domain on the outer membrane P1 protein (OMP) of Haemophilus influenzae type b (Hib). Synthetic peptides were elaborated from the known primary sequences of the P1 protein of prototype Hib strains MinnA (OMP subtype 1H) and 8358 (OMP subtype 6U). By peptide mapping, antibodies are categorized into three groups: A, B and C. A first epitope on the P1 from strain MinnA was identified by the reactivity of one set of murine anti-P1 mAbs with the two overlapping peptides 11H and 13H, corresponding to amino acid residues 384-412 and 400-437, respectively. On the basis of their reactivity with both peptides, these mAbs were designated as group A. Anti-Id obtained from mice immunized with two group A mAbs reacted specifically with all group A mAbs. A second epitope on the same P1 protein was identified by the reactivity of the peptide 13H with another distinct set of murine anti-P1 mAbs assigned to group B. This group of mAbs did not recognize the peptide 11H. Murine anti-Id which were prepared against one group B mAb inhibited the attachment of this mAb to outer membrane preparations, whereas the binding of the other group B mAbs was not affected, suggesting that these mAbs represent a heterologous group of mAbs. The epitope(s) recognized by two human anti-P1 mAbs was (were) distinct from the ones recognized by murine mAbs since no reactivity with the peptides was observed. Similarly, the binding of the two human mAbs to the P1 antigen was not inhibited by anti-Id raised against group A or B mAbs. Interestingly, an epitope on a different P1 protein recovered from strain 8358 was identified by the reactivity of group C murine mAbs with the peptide 13U, which occupies the same position on the P1 protein as 13H but differs from the latter by 10 amino acid residues. Our studies demonstrated the presence of several distinct surface-exposed B-cell epitopes within the antigenic domain which was defined previously on the P1 protein of Hib MinnA. Furthermore, we showed the immunodominance of this region on two different P1 proteins. None of the mAbs, however, had a bacteriolytic or protective activity against Hib strains. We suggest that the surface-exposed immunodominant region on the OMP P1 of Hib do not induce protective antibodies against Hib infection. PMID- 1522799 TI - Binding of fibronectin and type II collagen to Staphylococcus aureus from bovine mastitis: reduction of binding after growth in milk whey. AB - The binding of fibronectin and type II collagen to Staphylococcus aureus strains isolated from bovine mastitis was found to be 20-80% lower for organisms grown in milk whey compared to those grown in tryptic soy broth (TSB). The reduced binding was accompanied by reduced surface hydrophobicity. The observed changes, after growth in milk whey, were not due to a mere adsorption of milk whey components. The binding of fibronectin and the degree of surface hydrophobicity of milk whey grown bacteria became similar to that of TSB-grown bacteria after periodate treatment, whereas trypsin or papain treatments had no effect. PMID- 1522800 TI - Enteropathogenicity of non-toxigenic Vibrio cholerae O1 for adult mice. AB - The enteropathogenic potential of 32 Vibrio cholerae O1 isolates that do not produce cholera toxin was examined in the orally inoculated, sealed adult mouse model. Live cultures (2 x 10(10) cfu/ml) of 7/16 clinical and 6/16 environmental isolates produced a positive intestinal fluid accumulation (FA) ratio that reached near maximum at approximately 5 h post-inoculation. Colony hybridization did not detect genes for cholera toxin, Escherichia coli heat-labile and heat stable toxins, or shiga-like toxins. FA activity did not correlate precisely with cytotoxic activities on Chinese hamster ovary (28/32 positive), Vero (29/32) or HeLa (25/32) cells. Certain clinical and environmental isolates of non-toxigenic V. cholerae O1 appear to be enteropathogenic for the mouse, providing evidence that they may have pathogenic potential for humans through an as yet undefined mechanism(s). PMID- 1522801 TI - Pasteurella haemolytica leukotoxin inhibits mitogen-induced bovine peripheral blood mononuclear cell proliferation in vitro. AB - In this study we demonstrate that partially purified Pasteurella haemolytica leukotoxin inhibits the proliferative response of bovine peripheral blood mononuclear cells (PBMC) to mitogens in vitro. Inhibition of PBMC proliferation did not appear to be due to cell death. Addition of a neutralizing anti leukotoxin monoclonal antibody restored a normal proliferative response. PMID- 1522802 TI - Amyloidosis and inflammatory bowel disease. A 50-year experience with 25 patients. AB - Amyloidosis is a rare but serious complication of inflammatory bowel disease (IBD), especially Crohn's disease (CD). It occurred in 15 of our 1709 patients with CD (0.9%) (706 with ileocolitis, 310 with colitis, and 693 with enteritis), but in only 1 of our 1341 patients with ulcerative colitis (UC) (0.07%), admitted to The Mount Sinai Hospital between 1960 and 1985. Eleven of the patients with CD who had amyloidosis had ileocolitis, 2 colitis, and 2 ileitis; these figures represent a frequency within each group of 1.6%, 0.6%, and 0.3%, respectively. Amyloidosis was thus associated 4.4 times more often with CD of the colon than with pure small bowel disease. We have added to this group of 15 patients the 5 cases of CD that were originally reported by Werther et al in 1960, plus another 4 (2 with UC and 2 with CD) who have been seen since 1985, making a total of 25 patients in this series, 22 with CD and 3 with UC. There was a striking male preponderance, 16 of 22, among patients with CD, although 2 of the 3 patients with UC were female. Amyloid disease was diagnosed at a mean age of 40 years, 15 years (range, 1-42) after the onset of CD. Six major forms of amyloidosis occurred: nephropathy, enteropathy, cardiomyopathy, hepatosplenomegaly, thyroid mass, and generalized amyloidosis. Renal disease with proteinurea and/or renal insufficiency occurred in 18 of the 22 patients with CD and in all 3 with UC. Nephropathy was by far the most common lethal manifestation of IBD-associated amyloidosis in this series. Nephrotic syndrome developed in 15 patients with CD and was accompanied by renal failure, the major contributor to mortality, in 10 of the 13 patients who died. Amyloidosis may be associated with suppurative or other extraintestinal manifestations of IBD. Fifteen of the 22 patients with CD who had amyloidosis also had suppurative complications of their bowel disease, although the other 7 had no recognizable suppuration. Extraintestinal manifestations were also common in this series, occurring in 12 of 22 patients with CD and in 2 of the 3 patients with UC; 6 of the 18 patients with nephrotic syndrome also had arthritis. However, there is no evidence that patients with IBD with amyloidosis have extraintestinal manifestations more frequently than do IBD patients without amyloidosis. Earlier reports of amyloid associated with IBD came from autopsy series. In recent years, biopsy has allowed diagnosis to be made during life.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1522803 TI - Central nervous system complications of thermal burns. A postmortem study of 139 patients. AB - We report a retrospective, clinicopathologic study of 139 patients who died during treatment of a severe burn. Fifty-three percent of the patients had central nervous system (CNS) complications-infections, cerebral infarcts and hemorrhages, metabolic encephalopathies, central pontine myelinolysis, and cerebral trauma. Children and adults were equally affected. Sixteen percent of the patients had a CNS infection. Candida species, Staphylococcus aureus and Pseudomonas aeruginosa caused almost 80% of them. S. aureus and candida caused cerebral microabscesses and septic infarcts. P. aeruginosa caused meningitis and infarcts due to meningitis. CNS infections arose as a result of spread from a systemic source. The major risk factors for CNS infection were an extensive burn, S. aureus endocarditis, and a burn wound infection due to candida or P. aeruginosa. Patients with burns of less than 30% of the surface area of their body, those without a systemic infection, and those in the first week after their burn were at low risk. Eighteen percent of the patients had cerebral infarcts. In almost half the patients, the infarcts were caused by septic arterial occlusions or other complications of the burn, viz, disseminated intravascular coagulation (DIC) and septic shock. In only one-third of the patients were infarcts due to atherosclerosis, atrial fibrillation, or other causes prevalent in the general population. Intracranial hemorrhages were only one-fifth as frequent as infarcts and were due to DIC and thrombocytopenia, caused by bacteremia. Diagnosis during life was difficult, because the neurologic picture of focal cerebral lesions and meningitis was indistinguishable from that of metabolic encephalopathies, and because many patients had more than 1 neurologic complication. However, our results suggest that a clinical approach that includes analysis of risk factors for CNS infection, cerebral imaging, examination of cerebrospinal fluid, and tests for DIC can lead to a neurologic and microbiologic diagnosis in most patients. PMID- 1522804 TI - Assessment of renal osteodystrophy in hemodialysis patients. AB - We performed a prospective study of 30 patients undergoing chronic hemodialysis to determine which of 6 generally available diagnostic procedures provided the most useful information for the assessment of bone disease in hemodialysis patients. The 6 procedures were: routine biochemical measurements, N-terminal parathyroid hormone (N-PTH), radiographic analysis of hands and clavicles, bone density determination by dual photon absorptiometry (DPA), deferoxamine stimulation test, and iliac crest bone biopsy. Serum N-PTH was elevated in 83% of patients but was not significantly associated with abnormalities of other biochemical parameters. No significant relationship was demonstrated between biochemical data and radiographic findings or between biochemical data and bone density by DPA. All patients with abnormal DPA had an elevation of N-PTH; therefore, DPA did not reveal any unsuspected disease. Bone biopsies were done in 20 patients and findings in each were consistent with uremic osteodystrophy, including osteitis fibrosa cystica in 11 patients and aluminum-associated bone disease in 2 patients. Six patients had mixed disease, and 1 patient had osteoporosis. Despite 11 positive deferoxamine tests, bone biopsy revealed aluminum deposition in only 7 of these patients, suggesting extraosseous aluminum accumulation in the remaining 4. Evaluation of the positive and negative predictive accuracies of DPA, x-ray analysis, N-PTH levels, and aluminum bone deposition revealed that normal DPA or x-ray findings do not exclude bone disease, that N-PTH level is a good marker for secondary hyperparathyroidism, and that a negative deferoxamine test excludes aluminum-associated bone disease. Discriminant analysis also reinforced these conclusions.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1522806 TI - The clinical epidemiology of poliomyelitis. 1941. PMID- 1522805 TI - Coronary artery disease risk factors in the Johns Hopkins Lupus Cohort: prevalence, recognition by patients, and preventive practices. AB - Known risk factors for coronary artery disease are very common in the Hopkins Lupus Cohort, in spite of the fact that the average patients age is only 38.3 years. Three or more known risk factors were found in 53% of patients. Risk factors for CAD were common even in patients not on a regimen of prednisone therapy during their cohort follow-up. Hypercholesterolemia increased significantly with greater average prednisone dose. Despite the frequency of risk factors, patients' awareness of the risk of CAD was low, with only 16.9% of patients believing they were at high risk for developing CAD within 5 years. In general, awareness of individual risk factors was lower in black than in white patients with SLE. Preventive practices were most commonly addressed towards hypertension. Preventive practices directed against obesity, hypercholesterolemia, and smoking were underutilized. Whether these known risk factors are sufficient in and of themselves to explain the high frequency of CAD in the cohort (8%) or whether they are "enabling" factors acting upon endothelium damaged by immune-complex disease cannot be addressed by this study. However, both further investigation of these risk factors and attention to lifestyle and pharmacologic approaches to risk factor reduction are indicated by this study. PMID- 1522807 TI - Tonsillectomy and poliomyelitis. I. Epidemiologic considerations. 1942. PMID- 1522808 TI - Some recent advances in the study of poliomyelitis. 1954. PMID- 1522809 TI - Prevalence of Clostridium botulinum type E and coexistence of C. botulinum nonproteolytic type B in the river soil of Japan. AB - Soil samples from 98 sites in the whole systems of four rivers in Japan were examined for the presence of Clostridium botulinum. Type E organism was prevalently shown throughout the whole river systems including upper part; detection rates of type E toxin in soil culture ranged from 33 to 82%. This type was also detected in soil of adjacent mountainous district. Type B and C toxins were detected at 7% and 9% of the sites examined, respectively. C. botulinum type E and nonproteolytic type B strains were isolated from enrichment cultures of soil samples. These results suggest that the terrestrial origin of type E organism would be considered as one of the reasons for the high incidence of this organism in the sea areas, and prove that C. botulinum nonproteolytic type B exists in the soil of Japan. PMID- 1522810 TI - Role of the upstream region containing an intrinsic DNA curvature in the negative regulation of the phospholipase C gene of Clostridium perfringens. AB - The phospholipase C (alpha-toxin) gene (plc) of Clostridium perfringens was cloned into pUC19 and the effects of the upstream regions on expression of the plc gene were examined in Escherichia coli JM109. When the 0.7-kb region just upstream of the putative -35 site of the gene was deleted, production of phospholipase C increased approximately 10-fold. Northern blot hybridization analysis of the plc transcript showed that the upstream region inhibited transcription from the plc promoter. Nucleotide sequencing of this upstream region revealed that there are three periodically repeated (dA)5-6 tracts between positions -66 and -40 of the plc gene. A fragment containing this sequence showed anomalously slow electrophoretic mobility at low temperature, indicating that the region immediately upstream of the plc promoter is a locus of sequence directed DNA-bending. Nested deletions of the upstream region were created from its 5' end by exonuclease III and the effects of deletions on the expression of the plc gene were examined. When the 77-bp fragment containing the two (dA)5-6 tracts were deleted, phospholipase C production increased markedly. These results indicate that the intrinsic DNA curvature upstream of the plc promoter is involved in the negative regulation of the plc gene transcription. PMID- 1522811 TI - Adenovirus infection and specific secretory IgA responses in the intestine of infants. AB - We investigated adenovirus (Ad) infection of the intestine and Ad group-specific fecal IgA antibody responses in seven infants who were followed up from birth to 16 months to seven years of age. We isolated in tissue culture from fecal samples not only enteric Ad type 41 but also other Ads (types 2, 3, 5, 6, and 12). We also detected Ad antigens in the feces by ELISA at the times of infection with even non-enteric Ads, suggesting that a large amount of antigens were produced in the intestine. We found that repeated Ad infections with different serotypes were occurring and there were good fecal IgA antibody responses at each time. The infection seemed usually mild or asymptomatic: only one out of 23 occasions of the detected infections required hospitalization. PMID- 1522812 TI - Heat-labile toxin from Bordetella parapertussis induces contraction of smooth muscle cells in culture. AB - The ability of Bordetella heat-labile toxin (HLT) to contract various types of cells in culture was examined. HLT from B. parapertussis induced contraction of cultured smooth muscle cells from trachea, intestine, uterus and vas deferens as well as from aorta. The time required for contraction decreased as the dose of B. parapertussis HLT increased from 3 to 100 MID/ml. Upon exposure of cells to concentrations of toxin greater than 100 MID/ml, at least 2 hr was required for contraction. HLT from B. parapertussis did not affect cultured cardiac or skeletal muscle cells within 8 hr after the exposure to HLT (100 MID/ml). No effect on other types of primary culture cells or established cells such as Chinese hamster ovary (CHO) cells has been described. These data indicate that the primary target cells for HLT might be smooth muscle cells. PMID- 1522813 TI - Purification and characterization of secretory proteinase of Candida albicans. AB - Proteolytic activity of medically important yeasts was tested in both YCB-BSA agar and medium. All of 134 strains of Candida albicans, 13 of 18 strains of Candida tropicalis and 11 of 18 strains of Candida parapsilosis had this activity, while none of 52 Candida glabrata strains or of 11 Cryptococcus neoformans strains tested had proteolytic activity. Strains of C. albicans fell into five groups based on the level and time-course of in vitro proteinase productivity. Five strains randomly selected from each group were tested for pathogenicity in mice. The strain possessing the strongest pathogenicity was used to purify proteinase. The molecular weight of the proteinase was approximately 44,000 daltons and its isoelectric point was pH 4.2. Optimal pH of the proteinase was 3.2 and the enzyme was stable below pH 7.0 and lost its activity above pH 8.0 at 37 C in a 60-min incubation. The 23 amino acid sequence of the proteinase N terminus was determined. PMID- 1522814 TI - Characterization of an exo-beta-D-fructosidase from Streptococcus mutans Ingbritt. AB - An extracellular enzyme beta-D-fructosidase was purified from the culture supernatant of Streptococcus mutans Ingbritt and characterized. The molecular weight of the enzyme was 127,000 as determined by SDS-polyacrylamide gel electrophoresis. The enzyme was specific for levan which mainly consists of beta (2,6)-linked D-fructose and was also able to hydrolyze inulin, sucrose and raffinose at the activities of 13, 9 and 5% of that hydrolyzing levan, respectively. The pH optima for levan, inulin and sucrose were approximately 5.5, 6.0 and 5.0, respectively. The enzyme was optimally reactive at 55 C for levan. The enzyme was inhibited by Fe3+, Hg2+ and Zn2+ and not by either anionic or non ionic detergents. Paper chromatographic analysis revealed that the enzyme attacked levan by an exo-type mechanism. PMID- 1522815 TI - Seroepidemiology of spotted fever group rickettsiae in small field rodents in Japan. AB - To clarify the geographic distribution of spotted fever group (SFG) rickettsiae in Japan, small field rodents captured in endemic and nonendemic areas were screened for anti-SFG rickettsia antibodies by the immunofluorescence test. Among total 716 specimens tested, 73-75% of rodents were antibody-positive against Rickettsia japonica and/or Rickettsia montana, showing different degree of antibody-positive proportions among each species of the rodents. Interestingly, these profiles were not different in the rodents from each endemic and nonendemic areas, indicating that the SFG rickettsiae are prevailing in the wider areas where patients have not been found yet. PMID- 1522816 TI - Immunoglobulin G Fc fragment-binding proteins in Mycoplasma salivarium cells. AB - Cell proteins of Mycoplasma salivarium were separated by sodium dodecyl sulfate polyacrylamide gel electrophoresis, transferred to membranes, then examined for reactivity with human IgG molecules, the Fc fragment of human IgG, and concanavalin A (ConA). Multiple protein bands bound IgG, and most of them also bound ConA. One (corresponding to a molecular mass of 90 kDa) of the IgG- and ConA-binding bands intensely interacted with the Fc fragment of IgG. The reactivity of proteins eluted from the band with the Fc fragment, tested by dot blotting and ELISA, was inhibited (90%) by pre-incubation with IgG and to a lesser extent (50%), with IgM. Thus, M. salivarium contained a cellular protein with a molecular mass of 90 kDa, that bound the Fc fragment of human IgG. PMID- 1522817 TI - Nucleotide sequence of the arginine deiminase gene of Mycoplasma hominis. AB - The arginine deiminase gene of Mycoplasma hominis was amplified by the polymerase chain reaction, and its entire nucleotide sequence was determined. This gene consists of 1227 base pairs encoding 409 amino acids, and has 35.2% guanine plus cytosine content. Nucleotide sequence homologies of the arginine deiminase gene between M. hominis and M. arginini, and between M. hominis and M. orale were 82.1 and 80.8%, respectively, suggesting that this gene is highly conserved among arginine-utilizing Mycoplasma species. PMID- 1522818 TI - Arginine deiminase gene of an AIDS-associated mycoplasma, Mycoplasma incognitus. AB - Recently, we have demonstrated by molecular cloning that a strong immunosuppressive factor derived from Mycoplasma arginini is arginine deiminase. We show here that mycoplasma species identified in many of AIDS patients also bear the arginine deiminase gene. The implication of the arginine deiminase gene detected in AIDS-associated mycoplasma species is discussed. PMID- 1522819 TI - [Influence of heavy metal ions on the electrophysical properties of Anacystis nidulans and Escherichia coli cells]. AB - The influence of heavy metal ions (Ag+, Cu2+, Cd2+, Pb2+, Mn2+, Zn2+, Gd3+, 1 microM-1 mM) on Anacystis nidulans and Escherichia coli cells has been studied by means of electrophoresis and electro-orientation spectroscopy methods. It has been shown that changes of cell electrophoretic mobility (EM) and low-frequency (20 Hz) electro-orientation effect (EOE) observed with the increase of metal cation concentration characterize the adsorption of these ions on surface layers of cell envelopes. The degree and the character of these changes depend on cation valency and the initial value of cell EM. At the same time different changes of EM and EOE as a result of the multivalent cation adsorption allows to conclude that in that case the anisotropy of the cell surface increases. Cell damages were determined by changes in high-frequency EOE of cells which indicated the disturbance of barrier properties of their cytoplasmic membrane. Toxic effects of Ag+, Cu2+, Cd2+ ions on cells of both species and of Pb2+ on E.coli cells were observed. By toxic effects on the cytoplasmic membrane these ions could be placed in the order: for A.nidulans cells--Ag+ greater than Cu2+ greater than Cd2+; for E.coli cells Ag+ greater than Cu2+ greater than Cd2+ greater than Pb2+. Higher toxicity of heavy metals on E.coli cells seems to be connected with the more negative charge of deep layers of the cell surface. PMID- 1522820 TI - [Electrophysical analysis of Escherichia coli cell damage caused by silver ions]. AB - The influence of Ag+ (0.5-10 microM) on Escherichia coli K-12 cells was studied by electrophoresis and electro-orientation spectroscopy methods. It was shown that the pH-dependency of the cell electrokinetic potential (phosphate-citrate buffer with ion strength 0.02) practically didn't changed after Ag+ treatment, but in low-conductive media electrophoretical mobility of intact and inactivated by heat (70 degrees, 15 min) cells gradually decreased as the Ag+ concentration increased. It was due to the Ag+ adsorption on the cell surface and could not be used for the definite characterization of the cell damage. The high-frequency decrease in the cell electro-orientation spectrum shifted to the region of lower frequencies, K+ was excreted by cells, slight raise of the medium pH occurred and significant changes of cell osmotic properties were observed as a result of Ag+ action. All these changes showed the disturbance of barrier properties of the cytoplasmic membrane. Besides the damaging action of Ag+ on cell membranes increased with the decrease of pH and decreased after the addition of Mg2+, Ca2+ and Sr2+ in low concentrations. PMID- 1522821 TI - Flow cytometric assay for estimating fungicidal activity of amphotericin B in human serum. AB - We describe a simple and rapid bioassay for estimating fungicidal activity of Amphotericin B in human serum using flow cytometry. The method exploits the fact that Candida albicans damaged by Amphotericin B show a decrease in size and take up propidium iodide to exhibit a red fluorescence after deoxycholate treatment. These phenomena display characteristic dose dependencies, and their assessment permits serum fungicidal activity to be broadly grouped into three categories: (1) subfungicidal; (2) fungicidal; and (3) strongly fungicidal. In normal human serum, these three categories correspond to Amphotericin B concentrations of 0 less than or equal to 0.5 micrograms/ml, 0.75-1.5 micrograms/ml, and greater than 2 micrograms/ml, respectively. Pilot analysis of serum samples obtained from four patients undergoing Amphotericin B therapy confirmed the feasibility of using the flow cytometric assay for estimating drug fungicidal activity ex vivo. The method is very simple, generates results within 5 h, and could prove useful for monitoring therapy with this effective but toxic drug. PMID- 1522822 TI - Prevalence of infections affecting the child among pregnant women in Yaounde, Cameroon. AB - The prevalence of infections which have deleterious effects to either the mother or the fetus during pregnancy are unknown in Cameroon. To formulate appropriate antenatal screening policies for the Central Mother and Child Clinic in Yaounde, we tested random sera obtained from 1,014 stored samples previously obtained from pregnant women. One hundred and fifty sera were tested for the presence of the hepatitis B surface antigen (HBsAg), 544 for syphilis antibodies, 192 for antibodies to rubella and 192 for antibodies to Toxoplasma gondii. We found the HBsAg in 25.3% (38/150) of the subjects, antibodies against syphilis in 15.9% (87/544), antibodies to the rubella virus in 83.9% (161/192) and evidence of toxoplasma infection in 77.1% (148/192). Of the 38 HBsAg-positive subjects, 5.2% and 55.3% were positive for the HBe antigen and HBe antibody, respectively. We found a high prevalence for these infections in the antenatal clinical attendants. The data will be used to develop an appropriate control strategy for them. PMID- 1522823 TI - Evidence that bismuth salts reduce invasion of epithelial cells by enteroinvasive bacteria. AB - The effects of sublethal concentrations of bismuth salts on bacterial invasion of mammalian cells were investigated. Pepto-Bismol, bismuth subsalicylate, and bismuth oxychloride, produced by interacting bismuth subsalicylate and simulated gastric juice, in suspension at concentrations as low as 1.4 mM significantly interfered with the invasion of RPMI-4788 cells by two different strains of Yersinia enterocolitica. Invasion of the mammalian epithelial cells by other enteric bacteria was also reduced significantly by some of these bismuth salts. Commercially obtained bismuth oxychloride, bismuth sulfide, and sodium salicylate had no affect on invasion by Y. enterocolitica. Exposure of Y. enterocolitica 8081c to Pepto-Bismol for as brief a time as 5 min was sufficient to produce the inhibitory effect. Removal of bismuth bound to bacteria by sodium potassium tartrate did not reverse the inhibition. Electron-dense deposits are observed in Y. enterocolitica 8081c exposed to bismuth subsalicylate, suggesting that interference of invasion may result from bismuth permeation of the bacterial cell wall. PMID- 1522824 TI - Deposition of bismuth by Yersinia enterocolitica. AB - Yersinia enterocolitica 8081c cultures in exponential growth were incubated for 1 h in 0.1% microcrystalline bismuth subsalicylate (BSS) suspensions. Scanning electron microscopy (SEM) revealed microcrystals directly bound to BSS-treated bacteria. Energy dispersive spectroscopy (EDS) X-ray microanalysis of the attached microcrystals confirmed that the crystals were the microcrystalline BSS. X-ray spectra positive for bismuth were also obtained by SEM-EDS X-ray microanalysis of whole bacteria, suggesting metal incorporation into the bacteria in regions absent of bound microcrystals. Transmission electron microscopy of thin sections of embedded preparations of BSS-treated exponential-growth-phase bacteria showed electron-dense deposits in the periphery of the bacteria. Y. enterocolitica cultures that were in stationary phase at the time of incubation with microcrystalline BSS showed no evidence of the electron-dense deposits and EDS spectra were negative for bismuth. Bacteria incubated in the absence of microcrystalline BSS also lacked electron-dense deposits. Scanning transmission electron microscopy used in conjunction with EDS X-ray microanalysis to view and analyze semi-thick sections (250-300 nm) of embedded preparations of BSS-treated bacteria in exponential growth confirmed that the electron-dense deposits at the periphery of the bacteria are the sites of bismuth depositions. PMID- 1522825 TI - Parvoviruses are inefficient in inducing interferon-beta, tumor necrosis factor alpha, or interleukin-6 in mammalian cells. AB - To investigate a possible role of cytokines in parvovirus-mediated suppression of tumorigenesis, we tested in cell culture whether parvoviruses are able to induce interferon (IFN)-beta, tumor necrosis factor (TNF)-alpha or interleukin-6 (IL-6). Infection of rodent or human cells with the parvoviruses minute virus of mice (MVM), H-1 or adeno-associated virus (AAV) types 2 or 5 failed to induce expression of the luciferase or beta-galactosidase reporter genes transfected into these cells as constructs containing an IFN-beta promoter. Parvoviruses did weakly induce synthesis of TNF-alpha and of IL-6 in cell culture and could slightly enhance synthesis of these cytokines when induced by other agents. These in vitro data suggest that the rather unspecific tumor-suppressive properties of parvoviruses are unlikely to be attributable to stimulation of the synthesis of IFN, TNF or IL-6. PMID- 1522826 TI - Experimental Yersinia enterocolitica infection in rats: analysis of the immune response to plasmid-encoded antigens of arthritis-susceptible Lewis rats and arthritis-resistant Fischer rats. AB - Recently, experimentally Yersinia-induced arthritis in Lewis and SHR rats has been described as a potential animal model for analyzing the pathomechanism of reactive arthritis (Toivanen et al. 1986; Hill and Yu 1987). We could confirm that Lewis but not Fischer rats develop aseptic arthritis about 2 weeks after an intravenous inoculation of Yersinia enterocolitica, serotype 0:8 (Hill and Yu 1987). Moreover, we compared the antibody response to virulence-associated Yersinia antigens (Yops) of experimentally infected Lewis rats with that of Fischer rats using an enzyme-linked immunosorbent assay (ELISA) and immunoblotting. The ELISA results revealed a more rapid and vigorous specific IgG, IgA and IgM response for Lewis rats than for Fischer rats in the early state of infection. As demonstrated by immunoblotting, the IgG response was directed predominantly against the plasmid-encoded YopM, YopH, YopD and the V-antigen during the acute phase followed by antibodies against YopE and YadA. Although both rat strains seroconverted against this set of antigens, IgG antibodies to YadA were more prevalent and of higher titer in arthritis-susceptible rats compared to arthritis-resistant rats. PMID- 1522827 TI - Effect of intrauterine exposure to cocaine on acetylcholinesterase in primary cultures of fetal mouse brain cells. AB - The effect of in utero exposure to cocaine on the developmental pattern of acetylcholinesterase (AChE), a major regulator of the central nervous system neurotransmitter acetylcholine, was studied in fetal brain cell cultures collected from mice on gestational day 15 after maternal exposure to cocaine from gestational days 6-14. A significant decrease in total and specific activity (expressed per mg of protein) of acetylcholinesterase was seen throughout the culture period in the cells grown from the cocaine-exposed animals as compared to controls (p less than .002). Similarly, the total protein content of the brain cells grown from the cocaine-exposed animals was significantly decreased as compared to controls (p less than .03). Utilizing AChE as a biochemical marker, these studies have shown that in utero exposure to cocaine has an adverse effect on the normal developmental pattern of the production of acetylcholinesterase in cholinergic neurons in the fetal mouse brain. PMID- 1522828 TI - Behavioral effects of lead in monkeys tested during infancy and adulthood. AB - A total of 12 monkeys (Macaca fascicularis) were dosed orally from birth with 0 or 2000 micrograms/kg/day of lead as lead acetate. Blood lead concentrations of treated monkeys peaked at an average of 115 micrograms/dl by 100 days of age and decreased to a steady state level of 33 micrograms/dl after withdrawal of infant formula at 270 days of age. At 5-6 months of age, they were tested on a nonspatial discrimination reversal paradigm. At 2.5-3.0 years of age, they were tested on a series of nonspatial discrimination reversal problems, including irrelevant cues. As adults, performance was assessed on a differential reinforcement of low rate (DRL) schedule of reinforcement, a spatial delayed alternation task, and during training on a visual discrimination task for a visual psychophysics experiment. There were no or marginal deficits on the discrimination reversal task during infancy. Although lead-treated monkeys were impaired on this task as juveniles, they were less impaired than would have been predicted based on their history of blood lead concentrations. Treated monkeys exhibited decreased interresponse times and a greater ratio of responses per reinforcement on the DRL schedule compared to controls. Four of five treated monkeys were unable to learn the visual discrimination task without a remedial training procedure in which the relevant visual stimuli were arranged to appear as if they were on the response buttons. Treated monkeys were unimpaired on the delayed spatial alternation task. The results are interpreted as suggestive of an interaction between the behavioral history of the monkeys as infants with the results of later behavioral testing. PMID- 1522829 TI - Modulation of glial cell differentiation by exposure to lead and cadmium. AB - The influence of the neurotoxic agents lead and cadmium on human glioma cells (86HG-39, 87HG-31, 88HG-14, and A172) and rat glioma cells (F98 and RG2) was investigated in vitro by means of immunocytochemistry and growth data. Both heavy metals increased the growth rate, decreased the expression of differentiation markers (glial fibrillary acidic protein, S100 protein), and increased the expression of the malignancy marker transferrin receptor. The results indicate a decrease in the level of differentiation and impairment of glial cell function. Consequently, the neurotoxicity of Pb and Cd may be attributed to direct action not only on neurons but also on glial cells necessary for neuronal function. Possible molecular mechanisms are discussed. PMID- 1522830 TI - Euthanasia by decapitation: evidence that this technique produces prompt, painless unconsciousness in laboratory rodents. AB - Rapid euthanasia of laboratory rodents without the use of anesthesia is a necessary research technique whenever there is the likelihood of anesthesia or stress interfering with the chemistry of the tissues under investigation. Decapitation has long been the procedure of choice under such circumstances. Recently, however, the American Veterinary Medical Association (AVMA) panel on euthanasia recommended that decapitation be avoided on the grounds that the decapitated head may be conscious and suffering for as much as 15 seconds. The panel further recommended that if decapitation was scientifically necessary, the decapitated head be immediately immersed in liquid nitrogen. These AVMA guidelines now enjoy regulatory status; the recommendation that decapitation be avoided has thus caused considerable difficulty for all research requiring rapid, anesthesia-free collection of tissues. The scientific validity of these recommendations is consequently a matter of great practical as well as theoretical importance. The decision to discourage decapitation appears to have been based on a single literature report claiming that the EEG of the decapitated head revealed conscious suffering for more than 10 seconds (Mikeska and Klemm 1976). This review carefully examines the scientific literature on this subject. It is concluded that the report by Mikeska and Klemm of EEG activation in the decapitated head is correct, but that this phenomenon is also seen when the decapitated head is under deep anesthesia, and in normal brains under ether anesthesia or during REM sleep. Hence these findings do not demonstrate either consciousness or the perception of pain.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1522831 TI - Effects of postnatal aluminum exposure on choline acetyltransferase activity and learning abilities in the rat. AB - Young rats were treated by gastric intubation with aluminum lactate (0, 100, and 200 mg Al/kg/day) from postnatal days 5 to 14 to determine the treatment's influence on brain choline acetyltransferase activity and learning abilities. The results indicated that aluminum concentrations in the cerebral areas increased in parallel to plasma aluminum at the dose of 200 mg. In the same case, choline acetyltransferase activity was reduced. At postnatal days 50 and 100, the treated rats did not show alterations in their learning abilities in the 2 tests which are based on different motivations (avoidance of an aversive light or alimentary motivation) and different ways of achievement (pressing on a lever or running in a maze). A low reduction in the general activity, particularly in the radial maze test, was only observed in rats treated with 200 mg Al/kg/day. PMID- 1522832 TI - Neurotoxicity of acrylamide and 2,5-hexanedione in rats evaluated using a functional observational battery and pathological examination. AB - The clinical effects of two neurotoxicants, acrylamide and 2,5-hexanedione, were compared in rats using a functional observational battery (FOB), which includes a series of home cage and open-field observations, sensorimotor measurements, and physiological parameters. Neurotoxicity was assessed weekly in adult male Long Evans rats after initiation of IP administration of 9 doses of acrylamide (12, 15, or 50 mg/kg given 3 times a week) and 28 doses of 2,5-hexanedione (150, 225, and 350 mg/kg given daily). Using the FOB, it was possible to detect differences in neurotoxic effects of these two chemicals. Acrylamide significantly affected home cage posture, foot splay and time on the rotarod, whereas 2,5-hexanedione altered hindlimb grip strength and the approach response. Both compounds caused changes in ability to walk, right, and maintain agility on a rotarod within 21 days from initiation of toxicant administration. In addition, both compounds caused dose-dependent decreases in weight gain. Neuropathic changes were detectable at the highest dosages at 21 days in acrylamide-treated rats and at 28 days in rats treated with 2,5-hexanedione. Administration of acrylamide also decreased activities of neural esterases. This study indicated that the FOB could be used to detect evidence of neurotoxicity in rats treated with acrylamide and 2,5-hexanedione, with alterations evident even before pathological changes were induced by 2,5-hexanedione. PMID- 1522833 TI - Carboxyhemoglobin and brain blood flow in humans. AB - It has been shown that with increased carboxyhemoglobin (COHb) and associated decrease in blood oxygen-carrying capacity, a compensatory increase in brain blood flow (BBF) develops. The BBF response in humans has been shown to be quite variable. Two experiments were conducted in which humans were exposed to sufficient carbon monoxide (CO) to produce COHb levels up to 18.4%. BBF was measured by the method of impedance plethysmography. The first was a pilot study in which BBF in 14 men was studied after transient exposure to various concentrations of CO in air. BBF increased as a function of COHb but not to the same extent (or at all) in some subjects. In a confirmatory experiment with 12 men, BBF was measured once per h during a 4-h experiment. All 12 subjects received CO. The variation of the BBF response among subjects was large and statistically significant whereas the variation over time was not significant. Thus it appears that the magnitude of the BBF response is unique for a given subject and differs across subjects. These results may help predict CO-induced behavioral decrements in future studies if subjects whose BBF response to COHb is small or absent are also more susceptible to impairment by acute CO exposure. PMID- 1522834 TI - The effects of prenatal alcohol exposure on behavioral and neuroanatomical components of olfaction. AB - Prenatal alcohol exposure is associated with deficits in odor-associative learning in very young rat pups. One alternative explanation for these findings is that rather than a learning deficit per se, alcohol-exposed pups may display a sensory deficit. The present study was designed to examine the effects of prenatal alcohol exposure on behavioral and neuroanatomical components involved in olfaction. The subjects in this study were pups exposed to 35% ethanol-derived calorie (EDC) liquid diet from gestation days (GD) 6-20. Two control groups were included, a 0% EDC pair-fed and an ad lib lab chow group. In Experiment 1, respiratory response to a novel odor was examined in pups tested at either 3, 4, or 10 days of age. The 35% EDC offspring clearly detected the odor. Furthermore, there was an apparent alcohol-related development delay in respiratory rate as shown by a lower baseline respiratory rate at PN 3 relative to controls which was no longer apparent by PN 4. Experiment 2 examined the volume of two neuroanatomical structures involved in olfaction, the main olfactory bulb (MOB) and the vomeronasal organ (VNO) in 3-day-old pups. Prenatal alcohol exposure was associated with a decreased volume of the MOB although the VNO was unaffected. PMID- 1522835 TI - Recommendations for the use of folic acid to reduce the number of cases of spina bifida and other neural tube defects. AB - Spina bifida and anencephaly are common and serious birth defects. Available evidence indicates that 0.4 mg (400 micrograms) per day of folic acid, one of the B vitamins, will reduce the number of cases of neural tube defects (NTDs). In order to reduce the frequency of NTDs and their resulting disability, the United States Public Health Service recommends that: All women of childbearing age in the United States who are capable of becoming pregnant should consume 0.4 mg of folic acid per day for the purpose of reducing their risk of having a pregnancy affected with spina bifida or other NTDs. Because the effects of higher intakes are not well known but include complicating the diagnosis of vitamin B12 deficiency, care should be taken to keep total folate consumption at less than 1 mg per day, except under the supervision of a physician. Women who have had a prior NTD-affected pregnancy are at high risk of having a subsequent affected pregnancy. When these women are planning to become pregnant, they should consult their physicians for advice. PMID- 1522836 TI - Safety-belt use and motor-vehicle-related injuries--Navajo Nation, 1988-1991. AB - Injuries are the second leading cause of death among American Indians and Alaskan Natives; during 1986-1988, injuries accounted for 22% of all deaths (1). The risk for motor-vehicle-related injury deaths is nearly threefold higher among American Indians and Alaskan Natives than among the total U.S. population (age-adjusted death rates: 57.5 per 100,000 versus 19.5 per 100,000) (1-3). For residents of many rural, western, Indian reservations, age-adjusted motor-vehicle-related death rates are substantially higher; in particular, the rates for Navajos* are fivefold greater than for the total U.S. population (97.9 per 100,000 versus 19.5 per 100,000) (1) and almost three times the rate for all New Mexico residents (35.2 per 100,000) (4). To increase safety-belt use by front-seat occupants and thereby reduce motor-vehicle-related injuries, the Navajo Area Indian HealtH Service (IHS) Office of Environmental Health and Engineering, the Navajo Department of Highway Safety, and the Navajo Nation implemented a primary enforcement safety-belt use law and educational campaign. This report summarizes results of their effort. PMID- 1522837 TI - Increased HIV/AIDS mortality among residents aged 25-44 years--Baltimore, Maryland, 1987-1989. AB - From 1987 through 1989, overall mortality among Baltimore residents aged 25-44 years increased from 380.7 deaths per 100,000 residents to 452.6 deaths per 100,000, reflecting the substantial impact of human immunodeficiency virus (HIV) infection and acquired immunodeficiency syndrome (AIDS). To better characterize this increase in mortality, the Baltimore City Health Department analyzed information on death certificates from the Baltimore City Bureau of Vital Statistics for persons aged 25-44 years for 1987-1989. This report summarizes the analysis and characterizes HIV-infection/AIDS-related deaths among residents of Baltimore in this age group.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1522838 TI - Elevated blood lead levels in adults--United States, second quarter, 1992. AB - In the United States, more than 95% of elevated blood lead levels (BLLs) in adults result from workplace exposure (1). Beginning with this issue of MMWR, CDC's National Institute for Occupational Safety and Health (NIOSH) will report on a quarterly basis summary results of state-based surveillance programs for elevated BLLs (greater than or equal to 25 micrograms/dL) among adults (Table 1). In addition to the 18 states with blood lead surveillance programs previously reported (2), three other states maintain such activities, including Arizona (physician reporting of BLLs greater than or equal to 25 micrograms/dL, all ages), Florida (laboratory reporting of BLLs greater than or equal to 10 micrograms/dL, all ages), and Nebraska (laboratory reporting of BLLs greater than or equal to 10 micrograms/dL, all ages).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1522839 TI - Mifepristone (RU 486) compared with high-dose estrogen and progestogen for emergency postcoital contraception. AB - BACKGROUND: Mifepristone (RU 486) is a synthetic steroid with potent antiprogestational and antiglucocorticoid properties that provides an effective medical method of inducing abortion in early pregnancy. Since progesterone is essential for implantation, we tested the use of mifepristone for emergency postcoital contraception. METHODS: We studied 800 women and adolescents requesting emergency postcoital contraception who had had unprotected intercourse within the preceding 72 hours. A total of 398 women and adolescents were randomly assigned to treatment with 100 micrograms of ethinyl estradiol and 1 mg of norgestrel, each given twice 12 hours apart (standard therapy), and 402 women and adolescents were randomly assigned to receive 600 mg of mifepristone. RESULTS: None of the women and adolescents who received mifepristone became pregnant, as compared with four of those who received standard therapy; the difference in failure rates between the two regimens was not statistically significant. The number of pregnancies in each group was significantly lower than the number expected according to calculations based on the day of the cycle during which intercourse had taken place (P less than 0.001). In many subjects the stage of the cycle as calculated by menstrual history was inconsistent with measurements of plasma progesterone or urinary pregnanediol excretion. The subjects treated with mifepristone reported less nausea (40 percent vs. 60 percent) and vomiting (3 percent vs. 17 percent) on the day of treatment, as well as lower rates of other side effects, than the subjects treated with the standard regimen, but they were more likely to have a delay in the onset of the next menstrual period (42 percent vs. 13 percent). CONCLUSIONS: Mifepristone is a highly effective postcoital contraceptive agent that, if used more widely, could help reduce the number of unplanned and unwanted pregnancies. PMID- 1522840 TI - High-dose epinephrine in adult cardiac arrest. AB - BACKGROUND: Recent studies suggest that doses of epinephrine of 0.1 mg per kilogram of body weight or higher may improve myocardial and cerebral blood flow as well as survival in cardiac arrest. Such studies have called into question the traditional dose of epinephrine (0.007 to 0.014 mg per kilogram) recommended for advanced cardiac life support. METHODS: We randomly assigned 650 patients who had had cardiac arrest either in or outside the hospital to receive up to five doses of high-dose (7 mg) or standard-dose (1 mg) epinephrine at five-minute intervals according to standard protocols for advanced cardiac life support. Patients who collapsed outside the hospital received no advanced-life-support measures other than defibrillation before reaching the hospital. RESULTS: There was no significant difference between the high-dose group (n = 317) and the standard dose group (n = 333) in the proportions of patients who survived for one hour (18 percent vs. 23 percent, respectively) or who survived until hospital discharge (3 percent vs. 5 percent). Among the survivors, there was no significant difference in the proportions who remained in the best category of cerebral performance (90 percent vs. 94 percent) and no significant difference in the median Mini-Mental State score (36 vs. 37). The exploration of clinically important subgroups, including those with out-of-hospital arrest (n = 335) and those with in-hospital arrest (n = 315), failed to identify any patients who appeared to benefit from high-dose epinephrine and suggested that some patients may have worse outcomes after high-dose epinephrine. CONCLUSION: High-dose epinephrine was not found to improve survival or neurologic outcomes in adult victims of cardiac arrest. PMID- 1522841 TI - A comparison of standard-dose and high-dose epinephrine in cardiac arrest outside the hospital. The Multicenter High-Dose Epinephrine Study Group. AB - BACKGROUND: Experimental and uncontrolled clinical evidence suggests that intravenous epinephrine in doses higher than currently recommended may improve outcome after cardiac arrest. We conducted a prospective, multicenter study comparing standard-dose epinephrine with high-dose epinephrine in the management of cardiac arrest outside the hospital. METHODS: Adult patients were enrolled in the study if they remained in ventricular fibrillation, or if they had asystole or electromechanical dissociation, at the time the first drug was to be administered to treat the cardiac arrest. Patients were randomly assigned to receive either 0.02 mg of epinephrine per kilogram of body weight (standard-dose group, 632 patients) or 0.2 mg per kilogram (high-dose group, 648 patients), both given intravenously. RESULTS: In the standard-dose group 190 patients (30 percent) had a return of spontaneous circulation, as compared with 217 patients (33 percent) in the high-dose group; 136 patients (22 percent) in the standard dose group and 145 patients (22 percent) in the high-dose group survived to be admitted to the hospital. Twenty-six patients (4 percent) in the standard-dose group and 31 (5 percent) in the high-dose group survived to discharge from the hospital. Ninety-two percent of the patients discharged in the standard-dose group and 94 percent in the high-dose group were conscious at the time of hospital discharge. None of the differences in outcome between the groups were statistically significant. CONCLUSIONS: In this study, we were unable to demonstrate any difference in the overall rate of return of spontaneous circulation, survival to hospital admission, survival to hospital discharge, or neurologic outcome between patients treated with a standard dose of epinephrine and those treated with a high dose. PMID- 1522842 TI - A controlled trial of scheduled replacement of central venous and pulmonary artery catheters. AB - BACKGROUND: The incidence of infection increases with the prolonged use of central vascular catheters, but it is unclear whether changing catheters every three days, as some recommend, will reduce the rate of infection, It is also unclear whether it is safer to change a catheter over a guide wire or insert it at a new site. METHODS: We conducted a controlled trial in adult patients in intensive care units who required central venous or pulmonary-artery catheters for more than three days. Patients were assigned randomly to undergo one of four methods of catheter exchange: replacement every three days either by insertion at a new site (group 1) or by exchange over a guide wire (group 2), or replacement when clinically indicated either by insertion at a new site (group 3) or by exchange over a guide wire (group 4). RESULTS: Of the 160 patients, 5 percent had catheter-related bloodstream infections, 16 percent had catheters that became colonized, and 9 percent had major mechanical complications. The incidence rates (per 1000 days of catheter use) of bloodstream infection were 3 in group 1, 6 in group 2, 2 in group 3, and 3 in group 4; the incidence rates of mechanical complications were 14, 4, 8, and 3, respectively. Patients randomly assigned to guide-wire-assisted exchange were more likely to have bloodstream infection after the first three days of catheterization (6 percent vs. 0, P = 0.06). Insertions at new sites were associated with more mechanical complications (5 percent vs. 1 percent, P = 0.005). CONCLUSIONS: Routine replacement of central vascular catheters every three days does not prevent infection. Exchanging catheters with the use of a guide wire increases the risk of bloodstream infection, but replacement involving insertion of catheters at new sites increases the risk of mechanical complications. PMID- 1522843 TI - Brief report: autosomal dominant familial hypoparathyroidism, sensorineural deafness, and renal dysplasia. PMID- 1522844 TI - Cardiopulmonary resuscitation. PMID- 1522845 TI - Mifepristone (RU 486)--an abortifacient to prevent abortion? PMID- 1522846 TI - The states and health care reform. PMID- 1522847 TI - Health care reform in Minnesota. PMID- 1522848 TI - Medicine and war. PMID- 1522849 TI - Medicine and war. PMID- 1522850 TI - Medicine and war. PMID- 1522851 TI - Medicine and war. PMID- 1522852 TI - Mosaic expression of dystrophin in carriers of Becker's muscular dystrophy and the X-linked syndrome of myalgia and cramps. PMID- 1522853 TI - Primary care medicine in Canada. PMID- 1522854 TI - Primary care medicine in Canada. PMID- 1522855 TI - Primary care medicine in Canada. PMID- 1522856 TI - Primary care medicine in Canada. PMID- 1522857 TI - Informed consent in Africa. PMID- 1522858 TI - Informed consent in Africa. PMID- 1522859 TI - Informed consent in Africa. PMID- 1522860 TI - [Psychiatric nursing. Delirium: dilemma or not?]. AB - Delirium patients were often admitted to a psychiatric hospital in the past. This practise has to stop. Delirium is an illness which is caused by an organic factor, and in some cases, such as delirium tremens, there is a 5% mortality rate. If the causative factor is identified and rectified, and effective sedation is administered, the delirium patient should not be a problem for nursing staff to handle. A few simple, practical guidelines followed by the nursing staff can help the delirium patient recover within a week. PMID- 1522861 TI - Pets meet the needs of the lonely elderly. PMID- 1522862 TI - Media statements by drug experts can be dangerous. PMID- 1522863 TI - Health maintenance organisations. PMID- 1522864 TI - Update on pharmacology: pharmacokinetics. PMID- 1522865 TI - Disinfectants and spills of body fluids. PMID- 1522866 TI - Wound assessment and categorization. PMID- 1522867 TI - AIDS and TB: overlooked dimension. PMID- 1522869 TI - Cluster headache. PMID- 1522868 TI - AIDS education programme for children. PMID- 1522870 TI - Suicide and organ donation. PMID- 1522871 TI - AIDS and sport. PMID- 1522872 TI - Managing alcohol withdrawal states with oxygen and nitrous oxide. PMID- 1522873 TI - Money turmoil poses awkward questions. PMID- 1522874 TI - Last chance for British ass? PMID- 1522876 TI - Palaentology. Twilight of the pygmy hippos. PMID- 1522875 TI - DNA repair. Damage-limitation exercises. PMID- 1522877 TI - Cytokines. Can there be life without LIF? PMID- 1522878 TI - AIDS and virginity. PMID- 1522879 TI - Thyroid cancer after Chernobyl. PMID- 1522880 TI - Thyroid cancer after Chernobyl. PMID- 1522881 TI - Paralysed by politics, EPA delays spending any money on EMF research. PMID- 1522882 TI - Structure of porphobilinogen deaminase reveals a flexible multidomain polymerase with a single catalytic site. AB - The three-domain structure of porphobilinogen deaminase, a key enzyme in the biosynthetic pathway of tetrapyrroles, has been defined by X-ray analysis at 1.9 A resolution. Two of the domains structurally resemble the transferrins and periplasmic binding proteins. The dipyrromethane cofactor is covalently linked to domain 3 but is bound by extensive salt-bridges and hydrogen-bonds within the cleft between domains 1 and 2, at a position corresponding to the binding sites for small-molecule ligands in the analogous proteins. The X-ray structure and results from site-directed mutagenesis provide evidence for a single catalytic site. Interdomain flexibility may aid elongation of the polypyrrole product in the active-site cleft of the enzyme. PMID- 1522883 TI - Big increase for MITI budget emphasizes energy technology. PMID- 1522884 TI - Enhancements in biologically effective ultraviolet radiation following volcanic eruptions. AB - Aerosols injected into the stratosphere by large volcanic eruptions may induce ozone destruction through processes including heterogeneous chemical reactions. The effect of ozone reductions on surface ultraviolet irradiation is not obvious, however, because aerosols also increase the reflection of sunlight. Here we use a radiative transfer model to estimate the changes in biologically effective ultraviolet radiation (UV-BE) at the Earth's surface produced by the El Chichon (1982) and Mount Pinatubo (1991) eruptions. We find that in both cases surface UV BE intensity can increase because the effect of ozone depletion outweighs the increased scattering. PMID- 1522885 TI - BAAS embraces role of educating public. PMID- 1522886 TI - Rubbia prods Japanese to pay more to CERN. PMID- 1522887 TI - The genomic mutation rate for fitness in Drosophila. AB - The mutation rate per genome for local affecting fitness is crucial in theories of the evolution of sex and recombination and of outbreeding mechanisms. Mutational variation in fitness may also be important in the evolution of mate choice in animals. No information is available on the rate at which spontaneous mutations with small effects on fitness arise, although viability (probability of survival to adulthood) has been studied in Drosophila melanogaster. These experiments involved the accumulation of spontaneous mutations in the virtual absence of natural selection, in a set of independently maintained lines with a common origin. The rates of decline in mean and increase in variance among lines permit estimation of limits to the mean number of new mutations arising per generation (U) and the average homozygous effect of a new mutation of minor effect(s). For the second chromosome of D. melanogaster, the value of U is at least 0.17 (ref. 7), and (1-h)s is less than 0.02, where hs is the average decline in fitness of heterozygotes. As the second chromosome is about 40% of the genome, these data indicate a mutation rate per haploid genome of at least 0.42 for viability. Here we present similar data on the effects of homozygous spontaneous mutations on a measure of fitness in D. melanogaster. PMID- 1522888 TI - US rules hinder research on disposal of PCBs. PMID- 1522890 TI - Hurricane pounds Florida research facilities. PMID- 1522889 TI - Antisense c-myb oligonucleotides inhibit intimal arterial smooth muscle cell accumulation in vivo. AB - Synthetic antisense oligonucleotides have been used to dissect gene function in vitro. Technical difficulties prevented the use of this approach for investigating the effect of gene products in vivo. Here we report the use of local delivery of antisense c-myb oligonucleotide to suppress intimal accumulation of rat carotid arterial smooth muscle cells. Our results suggest that antisense oligonucleotides can be used to define the in vivo biological role of specific macromolecules in the blood vessel wall and could potentially serve as a new class of therapeutic agents for cardiovascular disorders. PMID- 1522891 TI - Expression cloning of a human DNA repair gene involved in xeroderma pigmentosum group C. AB - Xeroderma pigmentosum (XP) is a rare human autosomal recessive disease characterized by solar sensitivity, high predisposition for developing cancers on areas exposed to sunlight, and, in some cases, neurological abnormalities. XP cells are defective in DNA repair, and complementation of this defect has been used to identify eight genetic groups (A-G and variant). We have developed a simple, highly efficient complementary DNA expression system for use in human cells. Here we use this system to isolate a cDNA clone that restores the ultraviolet sensitivity and unscheduled DNA synthesis of XP-C cells to normal levels. The XP-C complementing clone XPCC encodes a highly hydrophilic protein which is composed of a predicted 823 amino acids and shares limited homology with the product of the yeast DNA repair gene RAD4. The XPCC transcript is undetectable by northern blotting in most XP-C cell lines examined. PMID- 1522892 TI - Blastocyst implantation depends on maternal expression of leukaemia inhibitory factor. AB - A critical point during mammalian pregnancy is the implantation of the blastocyst when the embryo attaches to the wall of the uterus. The autonomously developing preimplantation embryo then becomes dependent on the maternal environment for its continued development. Little is known about the regulation of implantation, except that a complex interaction between peptide and steroid hormones synchronizes the preparation of the uterus for implantation with the development of the embryo. Whether the implantation event is under maternal or embryonic control is also unclear (reviewed in refs 1, 2). We have previously shown that a cytokine, leukaemia inhibitory factor (LIF), is expressed in the uterine endometrial glands specifically on the fourth day of pregnancy. This burst of expression is under maternal control and always precedes implantation of the blastocyst. Here we report that transient expression of LIF in mice is essential for implantation. Females lacking a functional LIF gene are fertile, but their blastocysts fail to implant and do not develop. The blastocysts, however, are viable and, when transferred to wild-type pseudopregnant recipients, they can implant and develop to term. PMID- 1522893 TI - Mulling over mouse models. PMID- 1522894 TI - Reagents for the site-specific cleavage of megabase DNA. AB - The physical mapping of chromosomes will be facilitated by methods of breaking large DNA into manageable fragments, or cutting uniquely at genetic markers of interest. Key issues in the design of sequence-specific DNA cleaving reagents are the specificity of binding, the number of different sequences that can be targeted and the cleavage yield. PMID- 1522895 TI - Funding errors. PMID- 1522896 TI - Virology. How does variation count? PMID- 1522897 TI - "Surface tension" in the lungs. PMID- 1522898 TI - Fatal attraction to cyanobacteria? PMID- 1522899 TI - Isoprenylation in regulation of signal transduction by G-protein-coupled receptor kinases. AB - Rhodopsin kinase and beta-adrenergic receptor kinase (beta ARK) are related members of a serine/threonine kinase family that specifically initiate deactivation of G-protein-coupled receptors. After stimulus-mediated receptor activation, these cytoplasmic kinases translocate to the plasma membrane. Here we show that the molecular basis for this event involves a class of unsaturated lipids called isoprenoids. Covalent modification in vivo of rhodopsin kinase by a 15-C (farnesyl) isoprenoid enables the kinase to anchor to photon-activated rhodopsin. Mutations that alter or eliminate the isoprenoid, fully disable light specific Rhodopsin kinase translocation. Other receptor kinases (such as beta ARK), which lack an intrinsic lipid, are activated on exposure to brain beta gamma subunits of the signal-transducing G proteins, the gamma subunit of which bears a 20-C (geranylgeranyl) isoprenoid. Using chimaeric beta ARKs that undergo isoprenylation in vitro, we demonstrate that membrane association and activation of these kinases can occur in the absence of beta gamma. These results indicate that rhodopsin kinase (by means of an integral isoprenoid) and beta ARK (through its association with beta gamma) both rely on the function of isoprenyl moieties for their translocation and activity, illustrating distinct, though related, modes of biological regulation of receptor function. PMID- 1522900 TI - Association between GTPase activators for Rho and Ras families. AB - The ras-related low-molecular-mass GTPases participate in signal transduction involving a variety of cellular functions, including cell-cycle progression, cellular differentiation, cytoskeletal organization, protein transport and secretion. The cycling of these proteins between GTP-bound and GDP-bound states is partially controlled by GTPase activating proteins (GAPs) which stimulate the intrinsic GTP-hydrolysing activity of specific GTPases. The ras GTPase-activating protein (Ras-GAP) forms a complex with a second protein, p190 (M(r) 190,000), in growth-factor stimulated and tyrosine-kinase transformed cells. At its carboxy terminal end, p190 contains a region that is conserved in the breakpoint cluster region, n-chimaerin, and Rho-GAP. Each of these three proteins exhibits GAP activity for at least one member of the rho family of small GTPases. We have tested recombinant p190 protein for GAP activity on GTPases of the ras, rho and rab families, and show here that p190 can function as a GAP specifically for members of the rho family. Consequently, the formation of a complex between Ras GAP and p190 in growth-factor stimulated cells may allow the coupling of signalling pathways that involve ras and rho GTPases. PMID- 1522901 TI - Loss of gene function through rapid mitotic cycles in the Drosophila embryo. AB - The early developmental period in Drosophila is characterized by rapid mitotic divisions, when the body pattern becomes organized by a cascade of segmentation gene activity. During this process localized expression of the gap gene knirps (kni) is required to establish abdomen segmentation. The knirps-related gene (knrl) encodes a kni-homologous nuclear hormone receptor-like protein and shares the spatial patterns of kni expression. The two genes differ with respect to the size of their transcription units; kni contains 1 kilobase and knrl 19 kilobases of intron sequences. The consequence of this difference in intron size is that knrl cannot substitute for kni segmentation function, although it gains this ability when expressed from an intronless transgene. Here we show that the length of mitotic cycles provides a physiological barrier to transcript size, and is therefore a significant factor in controlling developmental gene activity during short 'phenocritical' periods. The required coordination of cycle length and gene size provides severe constraints towards the evolution of rapid development. PMID- 1522902 TI - Structure of the pancreatic lipase-procolipase complex. AB - Interfacial adsorption of pancreatic lipase is strongly dependent on the physical chemical properties of the lipid surface. These properties are affected by amphiphiles such as phospholipids and bile salts. In the presence of such amphiphiles, lipase binding to the interface requires a protein cofactor, colipase. We obtained crystals of the pancreatic lipase-procolipase complex and solved the structure at 3.04 A resolution. Here we describe the structure of procolipase, which essentially consists of three 'fingers' and is topologically comparable to snake toxins. The tips of the fingers contain most of the hydrophobic amino acids and presumably form the interfacial binding site. Lipase binding occurs at the opposite side to this site and involves polar interactions. Determination of the three-dimensional structure of pancreatic lipase has revealed the presence of two domains: an amino-terminal domain, at residues 1-336 containing the active site and a carboxy-terminal domain at residues 337-449 (ref. 6). Procolipase binds exclusively to the C-terminal domain of lipase. No conformational change in the lipase molecule is induced by the binding of procolipase. PMID- 1522904 TI - Women in science. PMID- 1522905 TI - California's money woes hit universities. PMID- 1522903 TI - Gene fusion with an ETS DNA-binding domain caused by chromosome translocation in human tumours. AB - Ewing's sarcoma and related subtypes of primitive neuroectodermal tumours share a recurrent and specific t(11;22) (q24;q12) chromosome translocation, the breakpoints of which have recently been cloned. Phylogenetically conserved restriction fragments in the vicinity of EWSR1 and EWSR2, the genomic regions where the breakpoints of chromosome 22 and chromosome 11 are, respectively, have allowed identification of transcribed sequences from these regions and has indicated that a hybrid transcript might be generated by the translocation. Here we use these fragments to screen human complementary DNA libraries to show that the translocation alters the open reading frame of an expressed gene on chromosome 22 gene by substituting a sequence encoding a putative RNA-binding domain for that of the DNA-binding domain of the human homologue of murine Fli-1. PMID- 1522906 TI - German institutes, industry seek to ease genetic engineering laws. PMID- 1522907 TI - NSF will experiment with fixed budgets in an effort to simplify grants process. PMID- 1522908 TI - Canadian research council found guilty of job bias. PMID- 1522909 TI - Japanese ministry requests large increase for competitive university grants. PMID- 1522910 TI - SKB announces UK redundancies and realignment. PMID- 1522911 TI - Wellcome Trust to list jobs, grants on line. PMID- 1522912 TI - Genetics-and-crime conference cancelled in clash with NIH. PMID- 1522913 TI - US university told to reveal unfunded NIH application. PMID- 1522914 TI - Occupational risks. PMID- 1522915 TI - Scope of human frontiers. PMID- 1522916 TI - Vaccine errors. PMID- 1522917 TI - [The phenomenon of hearing: an interdisciplinary discussion. II]. AB - This part of the paper deals with the neurophysiological background of speech analysis and hearing of music. Single vowel- and consonant-detector cells could be clearly separated at the colliculus and geniculate level (Kallert, Keidel). Musical stimulation is decoded at three levels: hair cells, geniculate, and auditory cortex. Human cortical evoked potentials represent rhythm, consonance, and (as DC-shift) the emotional content of music. Marked harmonics, even of single hair-cell vibrations and in single units of medial geniculate in combination with clock-cell networks, are the physiological basis of "harmony" in music. Dissonant stimuli are detectable at the cortical level in man (Finkenzeller, Keidel). PMID- 1522918 TI - First identification of drugs in Egyptian mummies. PMID- 1522919 TI - Improved efficiency in amplification of ancient DNA and its sequence analysis. PMID- 1522920 TI - Abiotic synthesis of amino acids under hydrothermal conditions and the origin of life: a perpetual phenomenon? PMID- 1522921 TI - Neural inducing factors in neuroblastoma and retinoblastoma cell lines. Extraction with acid ethanol. PMID- 1522922 TI - Chlorinated hydrocarbons in eels (Anguilla anguilla L.) from the River Rhine. PMID- 1522923 TI - Psychosocial stress affects urinary pteridines in tree shrews. PMID- 1522924 TI - German Society for Pharmacology and Toxicology. Autumn meeting. Graz, September 6 9, 1992. Abstracts. PMID- 1522925 TI - [Paroxysmal symptoms as initial expression of multiple sclerosis]. PMID- 1522926 TI - [Urination problems following total hip arthroplasty: insertion or not of an indwelling catheter?]. AB - OBJECTIVE: To assess the frequency of urine retention and of urinary tract infection after total hip replacement in order to: to minimize morbidity due to urine retention and urinary tract infection after total hip replacement; to limit the discomfort to the patient; to decrease the work load of the nursing staff, if possible. SETTING: University Hospital Rotterdam. DESIGN: Prospective, randomized. PATIENTS AND METHODS: In 61 patients after 63 total hip replacements the use of an indwelling catheter for 48 hours (group 1) was compared with catheterisation on indication only (group 2). RESULTS: Urine retention was less in group 1 than in group 2, 12/39 (31%) versus 15/24 (63%). In the subgroup males no difference was found between both groups. Urine retention was more frequent in elderly people. No other risk factors could be demonstrated. The number of patients with bacteriuria greater than 10(5) CFU/ml in group 1, 11/39 (28%) did not differ from group 2, 9/24 (38%). CONCLUSIONS: On the basis of these study results we recommend: In females: to use an indwelling catheter for 48 hours after total hip replacement; In males: to discuss this choice with the patient, because use of an indwelling catheter appears not to decrease the frequency of urine retention. The risk of discomfort caused by catheterisation and urine retention still exists. An indwelling catheter can, without increasing the risk of significant bacteriuria, eliminate this discomfort in the first 48 hours after operation. PMID- 1522927 TI - [Interobserver variation in the application of 2 disability scales in heart patients]. AB - OBJECTIVE: To examine the use of the Rankin scale for the assessment of disability in patients with ischaemic heart disease. SETTING: University Hospital Utrecht. DESIGN: Prospective interobserver study. PATIENTS AND METHODS: Fifty-two outpatients with heart disease (previous myocardial infarction, angina or both) were separately interviewed by four physicians (residents or specialists), viz., two cardiologists and two neurologists. The degree of disability was recorded by each observer on two different scales: the modified Rankin scale, a six-point scale developed from a neurological background, and the four-point scale developed by the New York Heart Association (NYHA). The agreement rates for the observers (23 in all) were corrected for chance (kappa-statistics; maximum 1.0). RESULTS: Total agreement on both scales was found for six of the participating 51 patients and for 10 and 11 patients when the Rankin scale and the NYHA scale were considered separately. Kappa values were 0.21 for the Rankin scale and 0.24 for the NYHA scale. The weighted kappa values were 0.56 and 0.47, respectively. The agreement among neurologists and cardiologists was comparable. CONCLUSION: The agreement rates of cardiologists and neurologists in the use of the Rankin scale and the NYHA scale in outpatients with heart disease are at best satisfactory. The good results of an earlier study with the Rankin scale in stroke patients were not achieved. This study indicates that the Rankin scale may be useful for the assessment of disability from heart disease particularly in patients with neurological disease, but there is room for further improvement. PMID- 1522928 TI - [Alpha-interferon antiviral treatment in 100 patients with chronic hepatitis B]. AB - In a retrospective study we investigated the antiviral effect of alpha-interferon in 100 patients with chronic hepatitis B who were treated in controlled trials conducted in Rotterdam (1985-1990). The aim of the treatment was to induce viral latency as indicated by HBeAg seroconversion. Alpha-interferon was administered in a dose of 5 mega-units per day subcutaneously. Sixty-two patients received alpha-interferon for 16 weeks combined with a second antiviral agent (acyclovir or descyclovir) while the other 38 patients were treated with alpha-interferon monotherapy during 20 to 34 weeks. Follow-up continued until 1 year after the start of therapy. Thirty-eight per cent of the patients exhibited an HBeAg seroconversion and 9% exhibited an HBsAg seroconversion indicating a complete eradication of the virus. After 1 year transaminase levels were normalised in 70% of the patients with HBeAg seroconversion compared with 22% in those without seroconversion (p less than 0.05). The combination therapy for 16 weeks and the alpha-interferon monotherapy of longer duration resulted in HBeAg seroconversion rates of 29% and 53%, respectively (p less than 0.05). The predominant adverse effects were fatigue, flue-like illness and leukopenia. Serious side effects such as seizures, psychosis and peripheral neuropathy occurred in seven patients. Side effects led to a dose reduction in 26% of the patients. Alpha-interferon is effective in terminating the virus replication in chronic hepatitis B. However, both the common mild and the uncommon major side effects necessitate intensive patient monitoring during alpha-interferon treatment. PMID- 1522929 TI - [Estimation of the potential number of donor organs in 1988 and 1989 in 13 hospitals with a major neurosurgical department]. AB - In the Netherlands the supply of donor organs for transplantation still fails to meet demand. This study deals with the total number of donors and donor organs available in the 13 Dutch hospitals with a large neurosurgical department. The number of kidneys that could have been donated was twice as large, hearts and livers five times as large, and pancreas 35 times as large as the numbers actually donated (in absolute numbers for 1988 and 1989 respectively 631 and 642 (kidneys), 173 and 204 (livers), 154 and 178 (hearts) and 239 and 285 (pancreata). Refusal by the potential donor's family was the main reason for not donating organs. PMID- 1522930 TI - [Subfascial lipoma of the forehead]. AB - Three patients with subfascial lipoma of the forehead are presented. These deeply placed lipomas are seen in up to fifty percent of the lipomas of the scalp. A characteristic feature is the intact skin line pattern over the tumour. Surgical treatment involves incision of the aponeurosis of the M. occipitofrontalis. PMID- 1522931 TI - [Carcinoid tumors: current knowledge in biochemical and endocrine aspects, diagnosis and treatment]. PMID- 1522932 TI - [Gilles-de-la-Tourette syndrome]. AB - Gilles de la Tourette's syndrome, a combination of multiple chronic tics and vocalizations, usually first occurring during childhood, is described in its history, symptomatology, genetics, etiology and therapy. Traditionally TS has been viewed either as an organic or as a psychogenic disorder. We propose an integrative concept combining both aspects. During a vulnerable phase in childhood a hypersensitivity of dopamine 2-receptors, induced by gene defects or perinatal trauma, leads to a lack of suppression of subcortical programs which discharge as tics. Tics are modified by multiple psychological contents (aggressive or sexual impulses, imitation of others) which tend to become independent of their origin. Severity of tics in the course of the illness is often dependent on the emotional status of the patient. Recent research focuses on the search for a major gene locus and the relationship between dopamine receptor hypersensibility and the disturbances of other neurotransmitter systems (norepinephrine, serotonin, endorphin). PMID- 1522933 TI - [Occupationally-induced carpal tunnel syndrome]. AB - In Western Europe the Carpal-tunnel syndrome (CTS) is rarely regarded as a work injury, but in the USA this syndrome is usually considered to be work-related compression of a peripheral nerve, and the labour unions are already concerned about it. The median nerve can be squeezed by the flexor tendons of the index and middle fingers. These tendons pass dorsally from the median nerve through the carpal canal, where the nerve is subject to pressure when the tendons stretch whilst the wrist is flexed. Measurements in the carpal canal confirm this mechanism and show that, whilst grasping with the muscle-strength necessary for many jobs, the pressure for the median nerve can rise as high as 450 mm Hg, if the wrist is in volar flexion. Among my own patients, 51% of the men and 28% of the women with CTS reported a clear connection between the onset of symptoms and an unfamiliar use of the hands. All these different activities had in common grasping with a volar flexed wrist. A dorsal splint was constructed, with a double joint that permits dorsal and lateral movements of the hand, but blocks flexion. Of 58 patients who carried on their working activities wearing this splint, 52 answered a questionnaire. Of the 42 patients without a prior CTS operation, 32 had remained perfectly well with the splint, 3 not at all. Two of the 10 patients with prior CTS operation reported no benefit. 13 of the 58 patients had a further operation following splint-treatment. It is concluded that proper design of the workplace and instruction of the workers could prevent many cases of work-related CTS. PMID- 1522934 TI - [Clinical and neurophysiologic markers of epilepsy with frontal lobe seizures in a series of patients diagnosed by video-EEG-telemetry]. AB - The general and ictal clinical features, including EEG findings, of 20 consecutive patients with frontal lobe epilepsy are presented. Diagnosis in all cases was based on video-EEG telemetry using strict criteria. Among the ictal motor phenomena, turning movements, dystonic, choreic and ballistic features prevailed. Ten patients vocalised during their seizures but loss of consciousness was rare, even if there was pronounced motor involvement. The duration of attacks generally was short, not exceeding 60 seconds in 18 patients, in whom sudden onset and cessation of seizures was noted. Ten patients showed inter-ictal epileptiform EEG activity and 19 had ictal abnormalities. The short duration and ictal clinical course may be helpful in differentiating frontal seizures from pseudoseizures. PMID- 1522935 TI - [Transcranial magnetic stimulation of patients with a single epileptic seizure]. AB - Transcranial magnetic stimulation (TMS) was performed in 21 patients who had had loss of consciousness of unknown origin, in order to find out whether TMS could help in finding the cause of unconsciousness and to estimate the risk of provoking a seizure in patients who had single fits in the past. Furthermore, EEG recordings with hyperventilation, photostimulation, 24-hour EEG and sleep deprivation EEG's were carried out as well as CCT or NMR investigation. In 15 patients the loss of consciousness was judged to be due to an epileptic seizure. None of the 21 patients had epileptic potentials in EEG recordings or showed an epileptic seizure during or after TMS, hyperventilation or photostimulation. One patient developed spike-wave activity in the sleep-deprivation EEG, another in the 24-hour EEG. On the basis of our results and previous reports, TMS does not seem to be helpful in the diagnosis of loss of consciousness of unknown origin. However, TMS can be used more liberally than hitherto in the study of motor pathways, in cases with a history of single epileptic seizures. PMID- 1522936 TI - [Simultaneous occurrence of sarcoidosis and MS or sarcoidosis within the clinical picture of multiple sclerosis?]. AB - Twelve years following the diagnosis of a histologically proved Sarcoidosis, a patient developed a central paresis of one lower limb. Two years later, tetraparesis, bladder dysfunction, ataxia and an internuclear bilateral ophthalmoplegia occurred. In CSF oligoclonal IgG without dysfunction of the blood brain barrier was found. On the basis of these data multiple sclerosis was diagnosed. PMID- 1522937 TI - [Cerebral multisystem atrophy in a patient with depressive hallucinatory syndrome. A case report]. AB - In a female patient, aged 47 years at the beginning, the successive appearance of extrapyramidal signs preceded by depression, paranoid-hallucinatory psychosis, autonomic and cerebellar dysfunction was followed up over a period of 8 years. Autopsy revealed--in accordance with the clinical symptomatology--both olivo ponto-cerebellar atrophy and a striatonigral degeneration. As a rule these changes are accompanied by dementia. The reported case is unusual in having first presented with severe depression and paranoid-hallucinatory symptoms. PMID- 1522938 TI - The five-five, ten-ten plan for Alzheimer's disease. PMID- 1522939 TI - Increased age affects properties characterizing behavioral plasticity in freely behaving Aplysia. AB - In the marine mollusc Aplysia, in vitro studies showed that the gill withdrawal reflex (GWR) and its neuronal substrates were altered by age. In contrast, age minimally affected the gill respiratory pumping movements (GPM) and its neuronal substrates. Based on the respective properties of the GWR- and GPM-pathways in vitro, we proposed that the more pronounced the effect of age, the greater the expression of plasticity in a pathway. This conclusion may hold for in vitro preparations, but it remained to be demonstrated in intact animals. Based on this conclusion, the GWR should exhibit greater plasticity than the GPM in intact animals. Using freely behaving Aplysia, we tested for plasticity of the GWR and the GPM in three age groups (young, mature, and old). The tests for behavioral plasticity were: Graded responses to varying stimulus strength, response decrement (or habituation) to repetitive stimulation, enhanced response to dishabituating stimuli, and the effect of the GWR stimulus on the GPM and the GPM stimulus on the GWR. The GWR in mature animals exhibited all four properties, but in old animals, graded responses and habituation were significantly altered and in young animals habituation and dishabituation were absent. The GPM exhibited fewer of the properties than the GWR, only graded responses and response decrement, both of which were generally the same in the three groups. We found that behavioral plasticity and age-induced plasticity are related in freely behaving animals and are consistent with in vitro findings. The effect of age on properties characterizing plasticity at both the behavioral and pathway levels is discussed. PMID- 1522940 TI - Active electrophysiological properties of spinal motoneurons in aged cats following axotomy. AB - The present study was designed to examine the effects of the aging process on the response of motoneurons to axotomy. Accordingly, in aged cats using intracellular recording techniques, the electrophysiological properties of axotomized lumbar spinal cord motoneurons were compared with those of control (nonaxotomized) motoneurons. In motoneurons that were subjected to axotomy, there was a reduction in axonal conduction velocity compared to that exhibited by control motoneurons. In addition, there were a number of changes in the configuration of the action potential following axotomy. The amplitude of the spike and the overshoot increased as did the slope of the soma-dendritic spike, whereas the delay between the initial segment and the soma-dendritic spikes decreased. The duration of the action potential's afterhyperpolarization increased; its amplitude remained unaffected although the calculated afterhyperpolarization current decreased. Following the spike, most of the axotomized motoneurons exhibited hyperpolarization undershoots and delayed depolarizations. Axotomized motoneurons exhibited a small decrease in the membrane potential and a reduction in the rheobasic current compared to control cells. The changes in the frequency distribution of axonal conduction velocity, afterhyperpolarization duration, afterhyperpolarization current and rheobase measurements suggest that aged motoneurons dedifferentiated following axotomy. These results indicate that axotomy, in aged motoneurons, results in the disruption of a variety of electrophysiological parameters and that the specific patterns of the responses that occur in axotomized motoneurons of adult cats also emerge in axotomized motoneurons of aged animals. PMID- 1522941 TI - Astroglia in Alzheimer's disease. AB - Amyloid deposits are characteristic of Alzheimer's Disease (AD) and there is growing evidence that amyloid may play an important role in the genesis of this neurodegenerative disease. This review discusses data which suggests that reactive astrocytes and microglia may be a necessary concomitant with amyloid to produce the neuropathology which manifests as AD. Several hypotheses and supporting data for mechanisms by which reactive astrocytes may mediate this neuropathology are presented. These include the possibility that amyloid induces excitotoxicity by interferring with astrocytic glutamate uptake, the possibility that amyloid has this effect via an action on a tachykinin-related receptor and the possibility that proteoglycans released by astrocytes may facilitate the deposition of amyloid plaques. Both symptomatic treatment to enhance cognitive function and treatment to stop the progression of AD are needed. It is hoped that answers to some of the unique questions raised here may provide new insight into the etiology and treatment of AD. PMID- 1522942 TI - Growth hormone secretion in Alzheimer's disease: 24-hour profile of basal levels and response to stimulation and suppression studies. AB - The 24-h growth hormone secretory pattern and GH response to growth hormone releasing hormone, the alpha 2-adrenoceptor agonist clonidine and the somatostatin-analogue SMS 201-995 were evaluated in 9 patients with Alzheimer's disease and 9 age- and body body-matched control subjects. The secretory profile did not differentiate between patients and controls. Both secreted the largest amount of GH during the early nighthours between 22.00-02.00, whereas the majority of daytime GH levels were below the assay's detection limit (0.4 ng/ml). No difference was found in GH response to GHRH between patients and controls. All subjects showed significantly enhanced GH secretion after GHRH. Dividing the patients into two groups according to age-of-onset (less than 60 years greater than), there was a trend toward larger GH responses to GHRH for the early-onset group. No other parameter differentiated the groups. GH levels after clonidine were blunted in all subjects but one AD patient, probably due to an age-dependent attenuation frequently observed in subjects over 45 years of age. Finally, the administration of the somatostatin-analogue did not render conclusive results, since spontaneous decline of GH concentration was already beginning 2 hours before the drug was given and continued steadily throughout the observation period. In conclusion, patients with only mild to moderate degree of Alzheimer's disease have no prominent changes in GH regulation. PMID- 1522943 TI - An evaluation of human neurophysin production in Alzheimer's disease: preliminary observations. AB - The concentrations of human neurophysins in the cerebrospinal fluid (CSF) of nine patients with Alzheimer's disease: Preliminary observations. (AD), and one patients with Pick's disease, were determined using specific radioimmunoassays (RIAs). Concentrations of vasopressin and oxytocin were also measured. Values were compared with those from 20 age-matched mentally normal individuals who were being treated for back pain. CSF levels of vasopressin-associated human neurophysin (VP-HNP) and oxytocin-associated human neurophysin (OT-HNP) in patients with AD (22 +/- 4 fmol/ml and 104 +/- 17 fmol/ml) were only 42% and 58% of those in the control subjects (p less than 0.0001, p less than 0.0004). Vasopressin levels for these patients (3.6 +/- 0.4 fmol/ml) were also significantly reduced to 51% of controls (p less than 0.007) and oxytocin levels were marginally (p = 0.092) reduced to 70% of controls. Because neurophysins and neuropeptides are gene-related products of vasopressin-neurons and oxytocin neurons, the data indicate that these neurons are functionally impaired in patients with AD. Plasma neurophysin values suggest this impairment is confined to neurons with centrally-directed axons. Data from the one patient with Pick's disease demonstrates that reduced CSF levels of neurophysins and hormones is not confined to Alzheimer-type dementia. PMID- 1522944 TI - Alteration in the pattern of nerve terminal protein immunoreactivity in the perforant pathway in Alzheimer's disease and in rats after entorhinal lesions. AB - Neurons in layer II of the entorhinal cortex consistently develop neurofibrillary tangles in Alzheimer's disease (AD). Experimental neuroanatomical studies have shown that these neurons give rise to the perforant pathway, a major excitatory projection to the hippocampal formation, which terminates in a discrete pattern in the outer portion of the molecular layer of the dentate gyrus. The distribution of two nerve terminal associated proteins, synaptophysin and NT75, was studied in the molecular layer of the dentate gyrus in AD and control cases to determine whether Alzheimer neuronal pathology is associated with loss of synaptic markers. In parallel studies, the effect of ablation of the entorhinal cortex in rats was evaluated. In AD as compared to controls, a decrease in synaptophysin immunostaining was evident in the terminal zone of the perforant pathway. NT75 nerve terminal immunostaining was too weak to interpret in the human hippocampal formation. Both synaptophysin and NT75 immunoreactivity were found in association with some neuritic plaques. In rats, entorhinal lesions resulted in diminished immunoreactivity for both synaptophysin and NT75 in the perforant pathway terminal zone. These results suggest that nerve terminal protein loss is a concomitant feature of neuronal pathology in AD. PMID- 1522945 TI - Muscarinic and nicotinic contributions to cognitive function and cortical blood flow. AB - Muscarinic receptor blockade in humans induces a transient memory deficit claimed to mimic aspects of Alzheimer's disease (AD). AD is also strongly associated with a specific blood flow abnormality in parietotemporal cortex; we previously showed that, despite induction of a dementia-like state, scopolamine does not produce these blood flow changes. In the present study, we administered both muscarinic and nicotinic receptor blockade (using scopolamine and mecamylamine) to seven elderly healthy subjects and measured subsequent changes in cognition and cortical perfusion, using the 133Xe inhalation method to quantify regional cerebral blood flow (rCBF). Results confirmed earlier findings of scopolamine induced memory deficit and frontal cortex flow reduction. Only mecamylamine, however, produced a perfusion deficit in parietotemporal cortex. All effects were transient and dose-dependent. These findings demonstrate the safety and feasibility of differential and combined blockade of nicotinic and muscarinic cholinergic blockade in human subjects. Furthermore, the nicotinic antagonist mecamylamine yields rCBF changes similar to those seen in AD, despite producing only minimal cognitive effects on its own. The rCBF and behavioral manifestations in AD may therefore reflect the functional loss of nicotinic receptors in addition to alterations in other receptor systems. PMID- 1522946 TI - Delayed acquisition of eyeblink conditioning in aged F1 hybrid (Fischer-344 x Brown Norway) rats. AB - We previously reported that the freely moving male Fischer-344 rat provides a useful model to demonstrate the progressive impairment of eyeblink conditioning associated with aging. However, because the youngest F-344 rats only performed at 60% of maximum, we ran the same experiment with hybrid rats and discovered most (i.e., those age 9-24 months) learned rapidly and exhibited conditioned responses on greater than 80% of trials by the end of two training sessions. In contrast, the aged rats (36 months) exhibited significantly fewer CRs on all four training days. However, unlike all ages of F-344 rats (3-30 months) which were run in our last study, these aged hybrid rats exhibited considerable improvement with extra training. These data indicate clear differences in the rate of learning between the two strains and suggest that even young F-344 rats may have deficits in the neural circuits which mediate eyeblink conditioning. Other anecdotal findings on differences between the two strains are noted. PMID- 1522947 TI - Regional effects of aging on dopaminergic function in the Fischer-344 rat. AB - To examine the consequences of aging on nigrostriatal (A9) and mesolimbic (A10) dopamine (DA) function, neurochemical and behavioral measurements were performed in male Fischer-344 rats 6, 12, 18, 24, and 30 months old. Regional analyses of dopaminergic overflow and uptake processes were examined using high-speed (5 Hz) in vivo electrochemical recordings and local drug application techniques. When potassium was used to elicit the presynaptic overflow of dopamine (DA) in striatal areas predominantly innervated by the substantia nigra, the amplitude of DA overflow was significantly lower in 24- and 30-month-old rats (p less than 0.05 and p less than 0.01 vs. 6 months, respectively). Furthermore, in ventral striatum (including the nucleus accumbens) which is innervated primarily by A10 DA cell bodies, potassium-evoked DA overflow release amplitudes were significantly lower in the 18, 24, and 30 month groups (p less than 0.01 vs. 6 months). In addition, age-related differences between the dorsal and ventral striatum were found in a preliminary investigation of DA diffusion and clearance. Local application of nomifensine, a DA uptake inhibitor, significantly increased (p less than 0.05 vs. control) the amplitude of the signal recorded after local application of 25-30 pmol DA in the ventral striatum of 6 month-old but not 24 month-old rats. High-performance liquid chromatography coupled with electrochemical detection (HPLC-EC) was used to analyze whole striatal DA levels, DA metabolite levels and turnover indices. However, no age-related differences in any of these variables were observed. Finally, a rod walking test was used to measure motor coordination and balance in animals prior to in vivo electrochemical recording.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1522948 TI - 2-Amino-3-(methylamino)propanoic acid (BMAA) bioavailability in the primate. AB - 2-Amino-3-(methylamino)-propanoic acid (BMAA) is a low potency excitatory amino acid present in the cycad plant that has been proposed as a factor in the high incidence of amyotrophic lateral sclerosis-parkinsonism dementia (ALS-PD) in the western Pacific region. We employed stable isotopic forms of BMAA to assess the oral bioavailability of this compound in cynomolgous monkeys (n = 3). The stable isotope labeled BMAA ([15N]-BMAA) was injected i.v. at the same time that the unlabeled compound was administered orally. Both forms of BMAA were then quantified in a 48h urine sample by gas chromatography-mass spectrometry (GC/MS). Following oral dosing, 80% of the administered BMAA was absorbed into the systemic circulation; thus, oral bioavailability was high and other routes of administration could not result in significantly higher circulating levels of BMAA for a given administered dose. PMID- 1522949 TI - Daytime sleepiness and performance among healthy 80 and 20 year olds. AB - This study investigated the relationship of daytime sleepiness and performance on a vigilance test in a sample of 10 healthy men and 13 women in their 80s (mean age 83.0 +/- 3.1 years) and 18 men and 12 women in their 20s (25.0 +/- 3.1). We hypothesized that "successfully" aged healthy individuals would have more daytime sleepiness with differentially greater decrements in performance than a younger comparison group. Daytime sleepiness was measured physiologically by the Multiple Sleep Latency Test (MSLT) and through self-report by the Stanford Sleepiness Scale (SSS). Morning and evening performance was measured with the Mackworth Clock Test of vigilance. The major findings were the absence of correlation between either MSLT or SSS daytime sleepiness with performance measures, no difference in daytime sleepiness between the old and young groups and performance decrements among the healthy elderly on all parameters. Results suggest that the modest decrements in performance among the elderly cannot be attributed to daytime sleepiness. PMID- 1522950 TI - The role of serotonin and dopamine in brain in the antidepressant-like effect of clonidine in the forced swimming test. AB - The effect of clonidine (0.1 mg/kg, i.p.), as a three-injection course, on behaviour in the forced swimming test was studied in rats injected intracerebroventricularly (i.c.v.) with 150 micrograms 5,7-dihydroxy-tryptamine (5,7-DHT) to destroy serotonin (5-HT) neurones or treated with 100 mg/kg (i.p.) (+/-)-sulpiride or 0.5 micrograms/0.5 microliter (-)-sulpiride in the nucleus accumbens. Clonidine significantly increased struggling and reduced floating and the effects were antagonized by both treatments with sulpiride but not by 5,7-DHT which markedly depleted 5-HT in brain. The results suggest that the mesolimbic dopaminergic system but not 5-HT neurones, plays a permissive role in the antidepressant-like effect of clonidine in the forced swimming test. PMID- 1522951 TI - Inhibition of tryptophan hydroxylase by (R)- and (S)-1-methyl-6,7-dihydroxy 1,2,3,4-tetrahydroisoquinolines (salsolinols). AB - The (R)- and (S)-enantiomers of salsolinol, the dopamine-derived tetrahydroisoquinolines, were found to inhibit the activity of tryptophan hydroxylase (TPH), prepared from serotonin-producing murine mastocytoma P-815 cells. Inhibition of TPH by salsolinols was found to be non-competitive with the substrate L-tryptophan. Tryptophan hydroxylase is composed of two elements with different kinetic properties in terms of cofactor (6R)-L-erythro-5,6,7,8 tetrahydrobiopterin and these two elements were inhibited by salsolinols in competitive and uncompetitive ways, respectively. Stereoselectivity of salsolinol was not observed, concerning the potency and the type of inhibition on PTH. These data indicate that salsolinols might be naturally occurring inhibitors of indoleamine metabolism. PMID- 1522952 TI - Characterization of cholinergic regulation of seizures by the midline thalamus. AB - This study determined the effects of injections of different cholinergic agents in the central medial intralaminar nucleus of the thalamus on seizures induced by intravenous injection of pentylenetetrazol. Injections of the cholinesterase inhibitor, neostigmine bromide, induced a stiff, tremulous state and lowered myoclonic, clonic and tonic seizure thresholds. The nicotinic agonist, tartrate, depressed arousal and facilitated all types of seizure, while its antagonist, d tubocurarine chloride, heightened arousal and transformed pentylenetetrazol induced convulsions, with tonic seizures occurring at a very low threshold without preceding myoclonic or clonic seizures or EEG spikes. The muscarinic agonist (+/-)pilocarpine hydrochloride, in very large doses, induced slight hyperactivity and facilitated tonic seizures but did not affect myoclonic or clonic seizures. Its antagonist, (-)scopolamine hydrobromide, slightly depressed arousal and myoclonic and clonic seizure thresholds. Injections of mixtures of agonists and antagonists (d-tubocurarine chloride + nicotine tartrate or (+/ )pilocarpine hydrochloride + (-)scopolamine) had little effect on spontaneous behavior or seizures. These results suggest that the midline thalamus regulates seizures and arousal, under the control of cholinergic neurotransmission. Nicotinic and muscarinic receptors have opposing roles in mediating these functions. PMID- 1522953 TI - Dizocilpine (MK-801) arrests status epilepticus and prevents brain damage induced by soman. AB - The involvement of the NMDA receptor in the neurotoxicity induced by soman, an organophosphorus compound which irreversibly inhibits cholinesterase, was studied in guinea pigs. The drug MK-801 (0.5, 1 or 5 mg/kg, i.p.) was given as a pretreatment before a convulsant dose of soman or as a posttreatment (30, 100 or 300 micrograms/kg, i.m.) 5 min after the development of soman-induced status epilepticus. Pyridostigmine, atropine and pralidoxime chloride were also given to each subject to counteract the lethality of soman. All subjects that were challenged with soman and given the vehicle for MK-801 (saline) exhibited severe convulsions and electrographic seizure activity. Neuronal necrosis was found in the hippocampus, amygdala, thalamus and the pyriform and cerebral cortices of those subjects surviving for 48 hr. Pretreatment with 0.5 or 1 mg/kg doses of MK 801 did not prevent nor delay the onset of seizure activity but did diminish its intensity and led to its early arrest. At the largest dose (5 mg/kg), MK-801 completely prevented the development of seizure activity and brain damage. Posttreatment with MK-801 prevented, arrested or reduced seizure activity, convulsions and neuronal necrosis in a dose-dependent manner. The NMDA receptor may play a more critical role in the spread and maintenance, rather than the initiation of cholinergically-induced seizure activity. PMID- 1522954 TI - Effects of dizocilpine (MK-801) and ethanol on the EEG and event-related potentials (ERPS) in rats. AB - Recent neurophysiological data have suggested an interaction of ethanol (EtOH) with the glutamate-NMDA receptor complex. For instance, low levels of alcohol have been found to inhibit the ion current, activated by NMDA in in vitro preparations. The present study extends these paradigms in order to evaluate the electrophysiological effects of ethanol and the nonspecific NMDA receptor antagonist, dizocilpine (MK-801) in awake, conscious rats. Twenty Wistar rats were stereotaxically implanted with electrodes, aimed at dorsal hippocampus, amygdala, thalamus and frontal cortex. Rats received the following drugs: saline (s.c.), 0.01 and 0.1 mg/kg MK-801 (s.c.); EtOH, 0.75 g/kg (i.p.); 0.75 kg EtOH plus 0.01 mg/kg MK-801; 0.75 g/kg EtOH plus 0.10 mg/kg MK-801. Five minutes of EEG was collected and event-related potentials (ERPs) recorded in response to an auditory "oddball" paradigm. Spectral analysis revealed that MK-801 (0.1 m/kg) produced significant increases in low frequency EEG components, at all sites (1-6 Hz) and decreases in higher frequencies (16-32 Hz). Whereas ethanol (0.75 g/kg) produced decreases in power in all frequency bands. The combined administration of EtOH and MK-801 produced some antagonistic effects on the EEG in the low frequency range. Evaluation of ERPs revealed that MK-801 (0.1 mg/kg) produced significant decreases in amplitude of the N1 and P2 components in the cortex, decreases in the P1 and N2 in the thalamus and a profound decrease in the P3 components in hippocampus and amygdala. Ethanol was also found to produce decreases in the N1 component in cortex. The administration of MK-801 and ethanol together did not produce significant interactions on ERPs. These studies suggest that antagonism of the NMDA receptor by MK-801 may produce some effects similar to those of ethanol, however, their combined administration did not produce synergistic effects within these dose ranges. PMID- 1522955 TI - Actions of a series of bisquaternary compounds on nicotinic acetylcholine receptors in insects: ligand binding and electrophysiological studies. AB - A series of bisquaternary ammoniums, with chain lengths of between 4-12 carbon atoms (C4-C12), have been tested for their ability to block acetylcholine-induced responses in the fast coxal depressor motor neurone (Df) of the cockroach (Periplaneta americana) and to displace [125I]alpha-bungarotoxin from membrane preparations of the CNS of the cockroach. The physiological studies showed that tetramethonium was inactive, whereas hexa-, octa- and dodecamethonium showed an enhanced ability to block acetylcholine-induced responses as the chain length increased. Decamethonium resulted in a slight increase in acetylcholine-induced depolarizations. Ligand binding studies showed that the ability of the compounds to inhibit the specific binding of [125I]alpha-bungarotoxin increased with size from C4-C12. The results show that neuronal nicotinic receptors in insects differ in aspects of their pharmacology from both the major subclasses of nicotinic receptors of vertebrates. PMID- 1522956 TI - Effects of tityustoxin and ouabain on release of acetylcholine from slices of cortex from the rat brain and on the acetylcholine content of cytoplasmic and crude vesicular fractions. AB - In this paper, the effects of tityustoxin and ouabain on the release and mobilization of ACh from cytoplasmic and vesicular stores of slices of cortex from the brain of the rat are described. Tityustoxin induced an increase of release of ACh which was time-dependent and this effect was accompanied by a concomitant decrease of the ACh, measured in cytoplasmic and crude vesicular fractions. Unlike tityustoxin, ouabain did not increase the release and synthesis of ACh during a 2 min period of stimulation but later, at 5, 10 and 15 min, ouabain increased the release and synthesis of ACh from incubated slices of cortex. After 10 min, ouabain caused a reduction of the content of ACh from cytoplasmic and crude vesicular fractions. PMID- 1522957 TI - Reversible cholinergic changes induced by AF64A in rat hippocampus and possible septal compensatory effect. AB - Ethylcholine aziridinium (AF64A) was injected intracerebroventricularly in rats, and the dose- and time-dependent effect of this treatment was measured on cholinergic markers in different areas of the brain. Choline acetyltransferase (ChAT) in the hippocampus was reduced by 0, 25, 40 and 50%, 4 days after administration of 0.25, 0.5, 1.0 and 2.0 nmol/side of AF64A. This effect was paralleled by a 0, 21, 38 and 48% increase in septal ChAT, at the same time and dose, respectively. Hippocampal and septal ChAT returned to normal by 14 days, following the two smaller doses of AF64A. Normal values of ChAT activity in the hippocampus were measured by 3 months post-1.0 nmol/side and by 12 months after 2.0 nmol AF64A/side. A transient secondary increase in septal ChAT was measured at 28 and 42 days after 1.0 nmol/side, after which no further changes were measured in this area. High affinity choline transport (HAChT) in the hippocampus showed a 35 and 25% decrease but only 14 and 7 days, after injection of 0.25 and 0.5 nmol AF64A/side, respectively. However, significant reductions by 45% at 14 days and by 65% at 4 days, were measured after the infusion of 1.0 and 2.0 nmol/side, respectively. This effect was significantly attenuated by 3 months and returned to normal by 12 months after treatment. Acetylcholinesterase (AChE) activity in the hippocampus was most severely affected by AF64A. Specifically, significant inhibition of 20% (by 7 days), 35% (by 7 days), 25% (by 2 days) and 30% (by 2 days) was observed at 0.25, 0.5, 1.0 and 2.0 nmol AF64A/side, respectively.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1522959 TI - Nursing student intake numbers. PMID- 1522958 TI - Regulation of amino acid uptake into cerebral microvessels. AB - The carrier-mediated transport systems, found in cerebral endothelium, are responsible for maintaining the nutrient milieu of the CNS. The objective of this study was to identify what factors might regulate the sodium-dependent A-system of neutral amino acid transport in isolated cerebral microvessels. The uptake of amino acids into isolated microvessels was measured using methylaminoisobutyric acid (MeAIB) a nonhydrolyzable A-analog of the A-system carrier. The results indicated that stimulation of adrenergic (both alpha and beta) receptors significantly (P less than 0.05-0.02) increased the uptake of MeAIB. While the muscarinic agonist carbachol alone did not alter the uptake of MeAIB, it blocked the stimulation evoked by adrenergic agonists. Furthermore, addition of the metal ion, aluminum also significantly (P less than 0.05) increased specific uptake of MeAIB by 95%, when compared to untreated controls. These results indicate that the uptake of neutral amino acids, through the A-system, into cerebral microvessels, can be modulated by adrenergic and cholinergic receptors, as well as the metal ion aluminum. Since the A-system of amino acid transport may control appropriate levels of amino acids in brain, modulation of the uptake of amino acids by adrenergic and cholinergic receptors and by aluminum, may be associated with an imbalance of amino acids and possible neurotransmitter defects in the CNS. PMID- 1522960 TI - User charges for hospital services: will they achieve their stated aims? PMID- 1522961 TI - [AIDS in Italy: an update to 31 December 1991]. PMID- 1522962 TI - [AIDS in the world up to 1 October 1991]. PMID- 1522963 TI - [Psoriasis: an autoimmune disease]. PMID- 1522964 TI - [Trials of the diagnostic potentials of TPA in tumorous and nontumorous lung pathologies in 303 cases]. AB - Serum tissue polypeptide antigen (TPA) has been determined in 271 patients with pleural or pulmonary neoplastic diseases (131) or with benign lung diseases (140). Using a cut-off of 95 U/L, TPA has a sensitivity and specificity of 65%. Therefore, TPA serum determination can suggest a diagnosis of malignancy, but its evaluation, as a single test, is not useful to differentiate between malignant or benign disease. TPA can be useful as an ancillary test in the follow-up of lung cancer therapy. PMID- 1522965 TI - [The diagnostic course in patients with hereditary ataxias and hereditary spastic paraparesis]. AB - A postal questionnaire was sent to all patients affected by hereditary ataxias and hereditary spastic paraparesis resident in the province of Turin (Italy) to study their diagnostic process. A 61% response rate was obtained. The mean time interval between onset and diagnosis was 6 years (1 to 32 years). The percentage of late diagnoses dropped from 59% before 1959 to 19% after 1970, mostly because a reduction of the interval between symptom onset and the first contact with the general practitioner. The onset with dysarthria and ataxia led to earlier neurologic consultation, but the whole time requested for the diagnosis was not modified. A reduction of the time needed for the diagnostic process may be important to address the family to an early genetic counselling. PMID- 1522966 TI - [The determination of sialic acid in cancer patients]. AB - The availability of a new rapid and reproducible laboratory test led to an easy dosage of sialic acid (AS) serum levels in neoplastic patients. This substance, involved in tumoral transformation and metastatic spread, has been evaluated in 278 neoplastic patients: 183 patients were affected by lymphoma (96 NHL and 87 HD), 60 by breast cancer and 35 by lung cancer. All groups of patients considered showed mean values of AS higher than healthy controls and the positive percentages, compared with cut-off levels, were respectively: NHL 71%, HD 70%, breast cancer 38%, lung cancer 89%. Even if the low specificity of this marker limits its clinical validity, AS, that seems related to clinical course of disease, could be useful in the monitoring of many neoplasms. PMID- 1522967 TI - [Adherence to a diet and the social aspects of patients with celiac disease]. AB - We studied the social behaviour and dietary habits of 335 coeliacs older than 6 yrs diagnosed in our paediatric gastroenterology unit by a mailed questionnaire, 156 patients (45.2%) answered all questions; their median age was 14.7 yrs (range 6-29). We found that the disease does not compromise educational achievement and working capacity of patients. A majority of our coeliacs are students (from primary school to university) and rather successful ones since 55% of them passed their previous year examinations. Some are already employed and work as clerks, artisans, masons or skilled workers. 89.6% of our patients reported to be on a strict gluten-free diet, 9% introduce small amounts of gluten and 1.4% are on a normal diet by their own decision. Coeliac patients originating from Northern Italy have more of their gluten-free foods home made and use more gliadin free cereals (rice, maize), whereas coeliacs originating from the Southern regions consume more ready made gluten-free foods. We have assessed the amount of gluten free products consumed monthly by our patients and their food preferences. Females eat less than males and prefer bread and flour based dishes, whereas males east more pasta and biscuits. PMID- 1522968 TI - [The personal and familial alcohol habits in groups of young men at their first military draft exam]. AB - In order to evaluate alcoholic consumption in a group of young men from an area in northern Italy, 834 subjects (18 years old) were examined at their first military check up. They compiled a questionnaire dealing with their own and their fathers' alcoholic consumption, social status, cultural habits, tobacco and drug abuse. 14.3% of the group examined were teetotalers. The alcoholic consumption of the youths was 31.44 +/- 48.8 DS alcohol g/a day versus their fathers' consumption of 44.52 +/- 42.12 DS alcohol g/a day. This difference is statistically significant (t = -8.1 p less than 0.001). No difference in alcoholic consumption was found between employed and unemployed subjects. Artisans and traders evidenced the highest levels of alcohol consumption (F = 2.58, p less than 0.009). The youths changed their alcoholic habits with respect to their own parents, preferring beer to wine consumption, although no change was observed in their approach to the alcoholic problems. The beer, like alcohol, remains a sociable and reassuring drink with positive connotations, even tough it is not considered a traditional Italian drink. PMID- 1522969 TI - [The estimation of p50 by the algorithm proposed by Siggard-Andersen. Its experimental assessment in critical patients]. AB - STUDY OBJECTIVE: To determine the ability of O. Siggaard-Andersen algorithm in the estimation of the "in vivo" p50 and standard p50 values from a single blood sample with sO2% less than or equal to 97. DESIGN: comparison between measured and calculated standard p50 values. SETTING: Intensive care unit. PATIENTS: thirteen cardio-pulmonary critical ill patients. Mean age of seventy-four years (range 53-84 years). MEASUREMENT: The experimental measurement of p50 standard (p50st sper) was performed tonometering the venous blood samples (60 specimens) using an IL-237 tonometer at 37 degrees C, with two different gas mixtures to obtain pCO2 at 5.33 kPa (DS = 0.06), and pO2 at levels to achieve sO2% values close to 50%. The gases's complete equilibration was not deemed important. The pO2 values were corrected to a pH of 7.40 using a Bohr factor = -0.48 and the p50 was taken by simple interpolation of points on the sO2%/pO2 diagram. Calculated standard p50 (p50st calc) and calculated "in vivo" p50 on the venous specimens (No. 60) and the correspondent arterial specimens with sO2% less than or equal to 97 (No. 40) were obtained by Siggaard-Andersen's computerized algorithm. Blood specimen analysis was performed by means of an ABL3 Radiometer gas analyzer and an OSM3 Radiometer oximeter. Statistical analysis was made by Anova test for liner regression. RESULTS: There was excellent correlation between the 60 experimental p50st determined by Siggaard-Andersen's oxygen dissociation curve on the same blood samples. The regression equation was: p50st sper = -0.79 + 1.21 x p50st calc, r = 0.90, R2 = 81.1%; with F = 249.5 and less than 10(-5). No good correlation was found between p50st and standards p50 calculated on arterial specimens (p50st calc art): p50 = 1.38 + 0.52 x p50st calc art, r = 0.52, R2 = 26.6%, F = 14 e P less than 10(-3). Regression of in vivo P50 calculated on correspondent venous samples (p50 ven) was: p50 ven = 0.79 = 0.77 x p50 art, r = 0.93, R2 = 87.2%, F = 256 and P less than 10(-5). CONCLUSION: Our results suggest that the curve describes the curve also at high saturation when it is not longer linear. Accurate measurement (including dishemoglobin percentage) and sO2% less than or equal to 97 are necessary. We did not perform experimental measurements of "in vivo" p50 but we postulate that as the p50st was well calculated so too would be the p50 "in vivo" at 37 degrees C. PMID- 1522970 TI - [Oral cancer in Himachal Pradesh]. PMID- 1522971 TI - [Captopril and hydrochlorothiazide in treating arterial hypertension in the elderly patient. An enlarged case series and verification of the results]. AB - A group of 171 hypertensive patients were treated using 100 mg captopril and 50 mg hydrochlorothiazide over a period of four months. The group was subdivided into two subgroups of 138 elderly patients and 33 patients aged under sixty all of whom had a systolic blood pressure of over 180 mmHg, or over 160 mmHg if they had undergone previous treatment using another drug. Patients were monitored after one month and at the end of hypotensive therapy. The study showed a statistically significant reduction of blood pressure in both groups. In the elderly group blood pressure diminished from a mean basal level of 198.8/104.5 mmHg to 140.4/80.5 mmHg, whereas in the adult group pressure values were reduced from 190.1/108.4 mmHg to 134.0/80.6 mmHg. These results match those of an earlier study and, in conclusion, the Authors affirm that this combinations is a suitable "geriatric drug" since it responds to the needs of elderly hypertensive patients. Using captopril and hydrochlorothiazide it is possible to improve the quality of life of elderly hypertensive patients who are otherwise notoriously difficult to treat. PMID- 1522972 TI - [Hashimoto's thyroiditis, idiopathic thrombocytopenic purpura (Werlhof's disease) and Steinert's dystrophia myotonica. A clinical case]. AB - The authors report a rare association: Hashimoto's thyroiditis, thrombocytopenic idiopathic purpura (Werlhof's disease) and Steinert's myotonic dystrophia. The authors outline the fingerprints of each disease, report particular syndromes and compare that association to data of partially reviewed literature. They suppose a suggestive pathogenetic connection among these diseases, due to the coexistence of altered genetic, endocrine and autoimmune factors and consequently impaired cell membrane permeability. PMID- 1522974 TI - [A personal case report of subacute sclerosing panencephalitis in an adult]. AB - The paper describes the case of a 37-year woman, with no past history of measles infection, who initially showed behavioral disorders, interpretative and reference deliria with a persecutory content. Extrapyramidal rigidity, bradykinesia, myoclonia, dementia, hyperpyrexia and coma with decerebrate rigidity subsequently appeared. Instrumental tests showed a spinal fluid status with intrathecal IgG synthesis and oligoclonal pattern, aspecific signs of widespread electric anomalies in the EEG. Encephalic CT and NRM were altered showing multifocal damage to the white substance. Anti-measles antibody titres were high in both spinal fluid and serum. Post-mortem histological tests confirmed the clinical hypothesis of subacute sclerosing panencephalitis. The paper reviews existing reports and pays special attention to cases of SSPE in adults and those cases with a psychiatric outcome. Lastly, the role of neuroradiological methods in the diagnostic iter is assessed. PMID- 1522973 TI - [Autoimmune polyendocrinopathy and chronic mucocutaneous candidiasis]. AB - A chronic mucocutaneous infection due to yeasts to the Candida genus can be part of the autoimmune polyglandular syndrome, described as APECS, APECED, SPA type I, CES. The authors describe the case of a young patient affected by mucocutaneous candidiasis, hypoparathyroidism and adrenal insufficiency. Chronic mucocutaneous candidiasis was diagnosed first in early childhood and was followed by the development of hypoparathyroidism (4 yrs) and adrenal insufficiency (5 yrs). The initial lesion of this syndrome is still unknown as the reason of the marked susceptibility to mucocutaneous candidiasis without systemic candidiasis. The treatment of mucocutaneous candidiasis has been improved by the introduction of orally active antifungal drugs as Ketoconazole, first, and fluconazole now. PMID- 1522975 TI - [Pheochromocytoma and autoimmune hypothyroidism]. AB - The association of multiple endocrine diseases is frequent and the coincidental involvement of the thyroid and adrenal glands is well recognized. On the contrary, two cases of hypo or hyperthyroidism have only been reported in literature: one concerning adrenal pheochromocytoma with simultaneous autoimmune hypothyroidism and another of a diffuse toxic goiter associated with pheochromocytoma. The purpose of the present report is to point out a new case of a pheochromocytoma associated with an autoimmune hypothyroidism in which the latter is florid and not biochemical. PMID- 1522976 TI - [The observations in a case of eosinophilic fasciitis]. AB - We present a typical case of eosinophilic fasciitis, with transient peripheral eosinophilia, indurative swelling of the legs, perivascular infiltrates of mononuclear cells and eosinophils of the subcutis and deep fascia, increased ESR, fever, anemia, complete response to steroids. We consider the literature on this topic, particularly concerning the following question: is eosinophilic fasciitis a distinct disease entity or a variant of scleroderma? PMID- 1522977 TI - Peroxy natural products. PMID- 1522978 TI - Pyrrolizidine alkaloids. PMID- 1522979 TI - Beta-phenylethylamines and the isoquinoline alkaloids. PMID- 1522980 TI - Innovations in design, material augment safety-eyewear comfort. PMID- 1522981 TI - Body and spirit. PMID- 1522982 TI - Shift work and its effects on fire fighters and nurses. PMID- 1522983 TI - Methodology in anti-emetic trials. AB - The most promising anti-emetic drugs are identified during preclinical testing. Phase I and II clinical studies are used to optimize doses and schedules for the various routes of administration. Most methodological issues arise in relation to phase III studies. A prospective, randomised, double-blind, parallel-subjects design is recommended. Stratification helps balance the factors influencing emesis between the 2 arms of a randomised study. The most important of these are the strength of the emetic stimulus, prior exposure to chemotherapy, age, sex and a history of chronic alcohol consumption. The evaluation of efficacy of an anti emetic should include its efficacy in controlling acute post-chemotherapy nausea and vomiting as well as anticipatory and delayed emesis. The side effects of an anti-emetic must also be considered since they may negate any anti-emetic advantage. Patients and observers have reported successfully evaluating these parameters using both categorical and linear-analogue scales. PMID- 1522984 TI - Measurement of quality of life in clinical trials. AB - Information on patients' quality of life (QOL) will give a more comprehensive evaluation of the treatment outcome than only measures of tumour response and survival. Psychosocial indicators have rarely been used in clinical trials. This may in part be explained by physicians' lack of familiarity with these measures, methodological insufficiency and a basic philosophical reason, i.e., most doctors tend to focus on curative treatment and not on palliative treatment. A series of QOL questionnaires has been validated in the last decade for use in cancer clinical trials. Selection of the optimal method in the given trial is important. The trial ought to be designed so the proportion of missing data is low. QOL should be used as an end point in selective trials with an optimal study design and with a study coordinator who is willing to collect QOL data. PMID- 1522985 TI - Managing treatment-induced emesis: a nursing perspective. AB - Patients with cancer undergoing treatment with chemotherapy or radiation therapy may experience a range of treatment-related side effects. One of the most common and most distressing side effects is treatment-induced emesis. The severity of the symptom is great enough to cause some patients to refuse treatments, delay appointments or discontinue therapy entirely. Experiencing treatment-induced nausea and vomiting can create a spectrum of issues for patients and their families and seriously influence their quality of life. Managing nausea and vomiting induced by cancer therapy is of critical importance. A team approach, inclusive of the patient, can be most effective. Nurses play a pivotal role in assessing patterns of nausea and vomiting and the usefulness of anti-emetic therapy, evaluating and updating treatment/care plans and helping the patient and family to cope with the disease and its treatment. PMID- 1522986 TI - [Implications of acquired immunodeficiency syndrome affecting the digestive system]. AB - Over the coming decades gastroenterology,--similarly to other branches of medicine,--will be confronted with AIDS and related disorders. In this article the gastrointestinal organ-associated symptoms are briefly reviewed with special reference to: esophagus, stomach, hepatobiliary system and the guts. Some special endoscopic problems of this field have also been mentioned. PMID- 1522987 TI - [Molecular genetic, laboratory and clinical study of serum amyloid P]. AB - Studying the gene polymorphism of serum amyloid P a common constituent of amyloid deposits two restriction fragment length polymorphism patterns were found among Hungarian rheumatoid arthritis (RA), juvenile rheumatoid arthritis (JRA), systemic lupus erythematosus (SLE) patients and healthy controls. Although no direct connection between DNA polymorphism and the frequency of amyloidosis in three patient groups was found, a marked predominance of the heterozygosity in all studied groups has been described. Authors found close correlation between the serum levels of SAP and CRP in juvenile rheumatoid arthritis, but failed to find the same correlation in SLE and healthy controls. Moreover, the serum level of CRP of heterozygous patients were significantly higher than that of homozygous patients within the juvenile rheumatoid arthritis patient groups. PMID- 1522988 TI - [Erythrocyte zinc-protoporphyrin/hem ratio--screening test for the detection of iron deficiency and lead exposure. Experience with the Hemofluorometer in Hungary]. AB - Increased zinc protoporphyrin/hem ratio (ZP) in erythrocytes caused by iron deficiency and/or lead exposure can be measured very simply and directly using a dedicated instrument, the Hematofluorometer. Clinical value of ZP test in detecting iron deficiency and lead exposure has been demonstrated by the authors in 465 females. Based on the literature and their own favourable experiences, the authors call attention to this useful screening method of preventive and diagnostic importance. PMID- 1522989 TI - [Exclusion of Sandhoff disease (Tay-Sachs 0 variant) by chorion biopsy]. AB - Transcervical chorionic villus sampling with ultrasound guidance at the 11-th week of pregnancy was made at a woman with the history of one lethal case of Sandhoff disease. The total hexosaminidase and the hexosaminidase A were determined. At the 16-th week amniocentesis was performed and the characteristic enzymes were determined from the amniotic cell culture. The results of the examinations made possible to advise the patient to carry out the pregnancy. The examinations after delivery confirmed the newborn to be a carrier. PMID- 1522990 TI - [Miklos Melczer M.D. (1891-1985)]. PMID- 1522991 TI - [Gusztav Barczi, M. D. (1890-1964)]. PMID- 1522992 TI - [Are we heading the wrong way?]. PMID- 1522993 TI - Neurological and skeletal outcomes in 113 patients with closed injuries to the cervical spinal cord. AB - Neurological and skeletal outcomes were evaluated in 113 patients for one year following closed lower cervical spinal cord injuries. The extent of neurological recovery did not depend on surgical versus nonsurgical management, or the degree of spinal angulation, vertebral displacement, spinal stenosis, or inferred mechanism of injury based on the initial plain cervical x-rays. Assessment of skeletal outcomes demonstrated significantly less vertebral angulation, more rapid stabilization, and less anterior callus formation among the patients in the surgical group. In addition, the surgical patients had marginally shorter lengths of hospitalization. PMID- 1522994 TI - Motor vehicle crashes and spinal injury. AB - Accident reports for 67 patients admitted to 3 spinal cord injury units in Australia in 1987 as a result of motor vehicle accidents were examined. Two thirds of the accidents occurred during the Friday-Saturday-Sunday leisure period and about 60% occurred during the November-February Australian summer holiday season. This conforms to the general Australian pattern of road trauma which is predominantly a consequence of leisure travel. The likelihood of a road traffic injury resulting in damage to the spinal cord was highest for motorcyclists whose average age was 22.7, lower than that for vehicle drivers (33.7) and vehicle passengers (38.1). However the most important finding is that most car occupants received their injuries when the motor vehicle overturned. As vehicle rollovers are relatively rare in the total spectrum of traffic crashes this distribution is thought not to have been previously reported. Some possible mechanisms of spinal cord injury are reviewed and engineering solutions to prevent future injuries are recommended. The paper also emphasises the unique opportunity for Australia to collect meaningful data on the causes of spinal injury and advocates the creation of an Australian Spinal Cord Injury Registry. PMID- 1522995 TI - An open trial of vacuum penile tumescence: constriction therapy for neurological impotence. AB - Sexual dysfunction is a frequent result of traumatic and non traumatic neurological disorders, including spinal cord injury, stroke, traumatic brain injury and autonomic neuropathy (for example, as may be seen in patients with diabetes mellitus). Although many methods have been suggested for the treatment of some of these problems in male patients, most are invasive and have a substantial morbidity. This is the report of a pilot trial of vacuum tumescence constriction therapy for 30 patients with chronic neurological impotence. Seventeen of these patients, following sexual counselling and training, decided to purchase such a device. At follow up, a mean of 21 months, over 50% of those who had purchased the device were still actively using it. The frequency of coitus increased from 0.3/wk to 1.5/wk (t = -5.7; p less than 0.0001). No significant morbidity was reported by patients. Vacuum tumescence constriction therapy shows promise as a noninvasive method for the treatment of neurological impotence. PMID- 1522996 TI - Transcutaneous nitroglycerin in the treatment of erectile dysfunction in spinal cord injured. AB - We have tested the erectile effect of penile applicated nitroglycerin plasters (Transiderm-Nitro 10 mg/24 hours) in 17 spinal cord injured men, who had responded to intracavernous papaverine injections with erections sufficient for vaginal penetration. The nitroglycerin plasters were applied on the skin of the penile shaft and a positive response was obtained in 12 men. A total of 5 men reported an erectile response sufficient for vaginal penetration after using nitroglycerin plasters at home. All 5 preferred to continue with this noninvasive treatment compared to papaverine injections. Our results indicate that men with spinal cord injury who need doses larger than 15 mg papaverine to obtain erection sufficient for vaginal penetration will not achieve this with nitroglycerin plasters. We suggest that this noninvasive treatment should be tested on spinal cord injured men before injection therapy is initiated. PMID- 1522998 TI - Return to work after spinal cord injury: the potential contribution of physical fitness. AB - The history, physical characteristics and fitness status of 60 persons who had sustained a spinal cord injury at least 3 years previously were considered in relation to current occupation. All subjects had completed their education, 39 being gainfully employed and 21 unemployed. The general characteristics of the sample, mainly beneficiaries of the Quebec Automobile Insurance Plan, were typical of spinal cord injured individuals in North America. The working group had a significantly higher current level of education than those who were unemployed (p less than .01). In terms of physical fitness, the workers were lighter, with a lower body mass index and a higher aerobic power (p less than .05). Isokinetic testing suggested a trend toward a higher peak torque in the workers. The total work performed (Nm.kg-1) during an isokinetic endurance test (25 biphasic contraction at 180 degrees.sec-1) was significantly higher in the workers, suggesting that such muscular endurance might be even more useful than greater peak isokinetic strength during vocational activities. However, the likelihood of employment was unrelated to habitual patterns of either aerobic exercise or overall physical activity. No significant differences of physical fitness or physical activity habits were found between workers holding sedentary versus physically demanding jobs. The results verified the positive relationship between physical fitness (body composition, aerobic power, muscular endurance) and the gainful employment of paraplegics, but failed to show any significant relationship between physical fitness and the acceptance of physically demanding work by such individuals. PMID- 1522997 TI - Mechanical plus pharmacological prophylaxis for deep vein thrombosis in acute spinal cord injury. AB - This pilot study assessed the effectiveness of external pneumatic compression (EPC) with gradient elastic stockings (GES) and low dose heparin (LDH) in the prevention of deep vein thrombosis (DVT) in acute spinal cord injured (SCI) patients in the first 14 days following injury. Twenty-one consecutive patients within 48 hrs of injury with acute C2 through T12 motor complete or nonfunctional motor incomplete spinal cord lesions were enrolled. 125 I fibrinogen scanning was performed daily. A positive scan was confirmed by venography. Thrombosis was demonstrated in 1/19 patients. A control group from a previous study confirmed thrombosis in 6/17 patients (p = 0.04). Comparison of extent of thrombosis demonstrated a reduction in the treated group (p = 0.02). This pilot study demonstrates that EPC with GES plus LDH may be an effective prophylactic regimen in these patients. PMID- 1522999 TI - Maximal exercise response of paraplegic wheelchair road racers. AB - The maximal metabolic responses of 11 paraplegic wheelchair road racers were evaluated with 2 wheelchair exercise protocols: increasing speed and increasing resistance. The maximal heart rates, minute ventilations and oxygen uptakes were similar for the 2 tests, indicating that either protocol is suitable for maximal wheelchair dynamometer exercise tests for groups. The resulting data were then compared to published data on maximal arm exercise by athletic and non athletic paraplegics and ambulatory males of the same age group. The combined mean values for both exercise tests of maximal oxygen consumption rate (VO2max = 37.4 ml/kg/min), minute ventilation (VE = 109.4 l/min), respiratory exchange quotient (RQmax = 1.18) and heart rate (187 beats/min) are in the mid range of reported data on wheelchair athletes. The mean RQ and heart rate values were similar to those achieved by ambulatory individuals performing maximal exercise tests. The mean VO2max of 37.4 ml/kg/min in our subjects is comparable to that achieved by sedentary ambulatory males of this age group. The data and the comparison to published data suggest several conclusions: in some parameters elite male paraplegic road racers have maximal values similar to those of ambulatory males, and in others they have maximal values substantially lower than might be expected; there is considerable variability among paraplegics in the metabolic responses to maximal exercise, most likely related to differences in cardiovascular fitness; and paraplegics can improve their cardiovascular fitness by training. PMID- 1523000 TI - Symptomatic postprandial hypotension in high paraplegia. Case report. AB - Symptomatic postprandial decrease in blood pressure has been described in patients with various autonomic disorders, but not in patients with spinal injuries. Presented herein is a 31 year old female patient with traumatic complete paraplegia under the T3 level, in whom postprandial hypotension (PPH) was observed. The PPH was preceded by an increase in insulin level and was followed by an acceleration of heart rate. Oral caffeine prevented the hypotension and alleviated the symptoms. It is suggested that the PPH might be manifested as a result of damage to an upper thoracic spinal baroreflex. Clinical investigation of PPH is recommended for patients with high paraplegia. PMID- 1523001 TI - Recurrent dislocation of the hip in adult paraplegics. AB - Recurrent dislocation of the hip is rare and has not previously been reported in adult paraplegics. This paper describes 3 cases. In one patient it was spontaneous, occurring 16 years after the original injury and was associated with a flexion-adduction contracture of the hip and a shallow acetabulum. One case occurred after minor trauma in a patient who experienced flexion-adduction spasms of the hip. In the third patient the condition was secondary to posterior acetabular deficiency following a conservatively treated fracture dislocation. All 3 patients experienced symptoms of disabling autonomic dysreflexia during the episodes of dislocation. The importance of recognising and adequately treating hip injuries in patients presenting with paraplegia secondary to spinal cord injury is stressed. In patients with spastic paraplegia presenting with recurrent dislocation of the hip, operative treatment combining a soft tissue repair and a bone block to augment the acetabulum is recommended. PMID- 1523002 TI - An outline of the programme of rehabilitation medical services in the People's Republic of China: 1991-1995. PMID- 1523003 TI - Graves' disease complicating myelopathy. AB - BACKGROUND: Exophthalmos, supraventricular arrhythmias, and myxedema have been noticed among patients chronically paralysed due to myelopathy. A survey was conducted to document and explain the observation. METHOD: A long term care population of 77 male myelopathy patients aged 59 +/- 14 years (mean +/- 1 standard deviation), paralysed 19 +/- 11 years, were compared by exophthalmometry (Hertel instrument) with 53 male non myelopathy patients and hospital employees, aged 57 +/- 15 years, by review of electrocardiograms (EKGs) of record with 91 male non myelopathy hospital patients, aged 59 +/- 13 years, and by thyroid function tests with standard values. RESULTS: Abnormal ocular protrusion (greater than 22 mm) was found in 9 myelopathy patients (12%) and in none of the controls. Exophthalmos was bilateral in 7. The mean ocular protrusion was 17.2 +/- 3.6 mm for myelopathy patients and 14.9 +/- 3.9 mm for controls (p less than 0.001). Three exophthalmic patients had atrial fibrillation. Arrhythmias had been recorded in 186 of 1390 EKGs in 34 myelopathy subjects and in 63 of 377 EKGs in 25 controls. The ratios of supraventricular to ventricular arrhythmias were 2.8 for myelopathy patients and 0.7 for controls (p less than 0.02). Hypothyroidism was found in 2 of 74 patients tested, 2.7%. CONCLUSION: Exophthalmos, supraventricular arrhythmias, and myxedema are unusually common among chronic myelopathy patients. Preceding Graves' disease with residual effects can be suggested as the explanation. PMID- 1523005 TI - How to weigh a patient who is over 350 pounds. AB - Every so often a physician needs to weigh someone who exceeds the weight limit of the standard office scale. This short tip describes an easy and quick method of obtaining the weight of someone who is over 350 pounds. PMID- 1523004 TI - The application of a modified neuroprosthetic hand system in a child with a C7 spinal cord injury. Case report. AB - A neuroprosthetic hand system developed at Case Western Reserve University has been modified for use by an 8 year old child with an incomplete C7 spinal cord injury. This system has been adapted to accommodate voluntary thumb and finger extension, and provides stimulated finger flexion and thumb position for lateral and palmar prehension. Three months were required to develop grasp with sufficient strength and coordination for functional use. This period consisted of: implantation and immobilization of percutaneous intramuscular electrodes; stimulated exercise of the muscles of the hand and forearm; programming grasp patterns; and system training. Functional assessments show that the neuroprosthetic hand system allows the subject to perform unilateral and bilateral tasks that were otherwise impossible or were previously performed bimanually. The ability to perform activities of daily living with one hand frees the contralateral upper extremity to be used either for balance which increases the work area, or to stabilize an object allowing manipulation with the instrumented hand. Telephone interviews suggest that the hand system is used on a consistent basis at home and school. This single subject application indicates that a stimulation system designed for adults with C5-6 spinal cord injuries can enhance hand function and facilitate independence in a child with a low level cervical lesion. PMID- 1523006 TI - A new way to support orthopaedic research? PMID- 1523007 TI - Discitis in children. AB - Discitis is usually a benign, self-limiting disease that is frequently misdiagnosed. The disease usually leads to spontaneous disc-space narrowing and end-plate irregularity, which require no treatment and rarely cause morbidity. PMID- 1523008 TI - Biomechanics of the human anterior cruciate ligament. Muscle stabilization and ACL reconstruction. AB - Several topics of debate surround the surgical reconstruction of the anterior cruciate ligament (ACL), including graft selection, reconstructive technique, and postoperative rehabilitation. The tensile properties of the human ACL and the role of this ligament in the normal kinematics of the knee have been addressed in the first part of this two-part review. This portion of the review will focus on the effects of reconstruction technique, initial graft tension, and muscular stabilization on knee kinematics. PMID- 1523009 TI - Biomechanical considerations in intramedullary fixation of lower-extremity fracture. AB - Since Gerhard Kuntscher's first cloverleaf design was introduced in the early 1940s, intramedullary nail geometry has become increasingly complex. Many design changes have been introduced, and these have had profound effects upon the mechanical performance of intramedullary devices, making them more versatile. The subset of long-bone fractures amenable to intramedullary fixation is expanding, largely because of these advancements in nail design. Selection of the appropriate nail and bone-nail construct for each fracture configuration requires a knowledge of basic biomechanical principles behind nail design and the implant host interface. Appropriate clinical application of this knowledge not only ensures the best possible intramedullary fixation of long-bone fractures, but it also aids in avoiding some of the complications that may occur. PMID- 1523010 TI - Anatomical variations of the median nerve at the wrist. AB - A comprehensive review of reported median-nerve variations at the wrist is presented. This includes motor-branch anomalies, multiple divisions of the median nerve, neural loops, and variations in association with aberrant muscles. Inadvertent injury to the median nerve during carpal tunnel surgery can be minimized if the anatomy is understood, variations are recognized, and adequate exposure is achieved. PMID- 1523011 TI - Clear cell sarcoma presenting as an interdigital neuroma. AB - The incidence of malignant soft-tissue sarcomas in the general population is approximately 1.4 per 100,000. Approximately 2% of all cancer deaths are attributable to these tumors. Presented is a case history of a soft-tissue malignant neoplasm that was originally thought to be an interdigital neuroma and that eventually required a modified Chopart's amputation. A review of the literature is presented on other soft-tissue malignant tumors that have an affinity for the foot and ankle. The intention of presenting this case is to caution physicians that malignant lesions can simulate a benign process and should always be considered in the differential diagnosis of any foot mass. PMID- 1523012 TI - Multifocal epithelioid hemangioendothelioma in bone. AB - The case of a 17-year-old male with multifocal, grade I epithelioid hemangioendothelioma of the right ankle and foot is presented. The major symptom was poorly localized ankle pain refractory to conservative management. Imaging studies, including roentgenograms, computed tomographic scan, and magnetic resonance imaging, revealed multiple lesions in the right distal tibia, talus, calcaneus, and first cuneiform. An open biopsy of the right talus confirmed the diagnosis, and treatment consisted of localized radiation therapy to the affected area. We review the literature of this rare neoplasm from the initial descriptions to current nomenclatures and conceptualizations of the tumor. PMID- 1523013 TI - Metastatic renal carcinoma in the hand: treatment with preoperative irradiation and ray resection. AB - Isolated metastatic renal-cell carcinoma of the hand is a rare disorder that requires aggressive management for pain relief, improvement of hand function, and prevention of further spread of disease. An unusual presentation of isolated, advanced metastatic renal-cell carcinoma in the left third metacarpal of the nondominant hand is presented. Localized preoperative radiation therapy was used prior to ray resection to decrease tumor bulk and vascularity. The patient is alive and disease free at 1 year postoperatively with a functional but impaired hand. PMID- 1523014 TI - Imaging rounds. Multifocal adamantinoma of the tibia and fibula. AB - The following is a description of the clinical and roentgenographic findings in a case exhibiting a condition of interest to the orthopaedic surgeon. Initial history, physical findings, and roentgenographic examinations are found on this page. The diagnosis and discussion of this case are presented on the following pages. PMID- 1523015 TI - Status epilepticus in children. The acute management. AB - Status epilepticus is a common pediatric emergency that may result in significant morbidity and mortality. This article provides a clinical update on generalized tonic-clonic status epilepticus in children and a practical approach to their initial stabilization and pharmacologic management. Only an organized approach to the initial stabilization and management of the child in status epilepticus will help prevent unnecessary complications and death. PMID- 1523016 TI - Update in medical toxicology. AB - This article examines some current issues in toxicologic care. First there is a review of the scope of pediatric poisonings and some aspects of initial management. Then there is a discussion of the decision-making process required to properly use gastric decontamination in the management of poisonings. Each of the common methods available--emesis, gastric lavage, activated charcoal, catharsis, and whole bowel irrigation--is discussed. Finally, several new and old antidotes are reviewed, namely naloxone, glucagon, bicarbonate, dimercaptosuccinic acid, digoxin-specific fab fragments, and flumazenil. PMID- 1523017 TI - Child abuse intervention in the emergency room. AB - The pediatrician and other emergency room caregivers are often on the frontlines in the identification and treatment of child abuse and neglect. The ability to recognize the possibility of intentional injury is crucial because immediate intervention may be necessary to prevent further harm to the child. The evaluation requires a careful taking of history, thorough physical examination, and detailed documentation. Reporting of suspected abuse or neglect is mandated and must be made to appropriate authorities. Follow-up of medical treatment, services, and available therapy should be emphasized to assure the continued safety of the child. PMID- 1523019 TI - Management of pediatric head injury. AB - This article on management of pediatric head injury reviews the pathophysiology and current therapy for traumatic brain injury in children. There is an emphasis on clinical protocols and algorithms that guide therapy to prevent or attenuate the deleterious effects of secondary brain injury as intracranial hypertension, hypotension, and hypoxia. PMID- 1523018 TI - Triage, initial assessment, and early treatment of the pediatric trauma patient. AB - It should be clear from this overview of triage, assessment, and initial care that early involvement by the leader of the trauma team is essential. Because operative intervention is so often necessary, the trauma team leader should be a surgeon with specialized training in trauma. The complex decision-making process involves prioritizing approaches by emergency room physicians, pediatricians, and surgical specialties in patients with multiple injuries. Even with single-system injury a rapid and logical approach to assessment and treatment is necessary in light of an overall longer term management plan. PMID- 1523020 TI - Pediatric maxillofacial trauma. AB - The accurate diagnosis and timely, appropriate treatment of soft-tissue and bony maxillofacial injuries in children are of critical importance due to the potential adverse impact of maxillofacial trauma on subsequent facial growth and development. Guidelines are provided to assist the pediatrician in the evaluation and treatment of minor and major facial injuries. PMID- 1523021 TI - Pediatric burns. An overview. AB - This article describes the management of burn injuries in children. It begins with an epidemiologic description of pediatric burns. Attention is given to emergency care, burn wound evaluation, operative management, and rehabilitative goals. PMID- 1523023 TI - Pediatric emergency medicine. PMID- 1523022 TI - Computerized diagnostic referencing in pediatric emergency medicine. AB - A well-qualified and dedicated pediatrician in a mid-Atlantic state recently cared for a 4-year-old child with a fever and a truncal rash. On the second visit the child was lethargic but seemed to improve with oral hydration and fever control. Twenty hours later the child's rash became petechial and the child returned moribund and died shortly thereafter. Looking for an emergency differential diagnosis on a 4-year-old child with fever and a truncal rash would have been cumbersome using traditional reference materials. With PEM-DXP, however, a nurse or secretary could have produced for the physician in 60 seconds a list of 12 emergency diagnoses to be considered. Rocky Mountain spotted fever would have appeared on that list. (Ten percent of patients with Rocky Mountain spotted fever have a maculopapular rash, and in 10% of those children the rash begins on the trunk.) This list might have prompted this physician to ask about a tick bite. A positive response would have been obtained. Possibly the tragic outcome, for both the child and the physician, could have been avoided. Children with urgent complaints are frequently cared for by physicians who are busy, tired, sleep-deprived, and stressed in many other ways. These physicians often have not read last month's medical journals in their specialty or even last year's journals. Yet the parents' expectation, and rightly so, is that their pediatrician or emergency physician has at his or her command and is bringing to bear on the care of their child the vast knowledge base of medical science as it pertains to their child's condition. It is a totally unrealistic expectation. By computerizing reference materials in ways that allow for selectively searching for and compiling information pertinent to a given presentation, however, we can move a bit closer to meeting both the parents' expectations of us and our own expectations of ourselves. PMID- 1523024 TI - Cardiac issues in the pediatric emergency room. AB - A great variety of problems referable to the cardiovascular system can prompt a visit to the pediatric emergency room. From the initial presentation of congenital heart disease, to the subsequent life-long management of these patients, to miscellaneous problems like Kawasaki disease and chest pain, the front-line pediatrician must be skilled in the recognition and early management of myriad complaints. This article focuses on information that can assist the emergency pediatrician in the evaluation and treatment of the cardiac patient from arrival in the emergency room until transfer of care to the pediatric cardiologist or inpatient staff. PMID- 1523025 TI - The infant with cyanosis in the emergency room. AB - The infant with cyanosis is a distressing medical presentation. The emergency room physician must be familiar with the diverse causes that may be underlying the event. An understanding of the pathophysiology along with a thorough history and physical examination will guide the physician toward appropriate intervention and management. PMID- 1523026 TI - Inhaled therapy in infants: why not nebulize glucocorticoids? PMID- 1523028 TI - Tuberculosis revisited. PMID- 1523027 TI - Of pneumograms and polysomnography. PMID- 1523029 TI - Temperature affects mechanics and stability during initial inflation-deflation of mature fetal lung. AB - Volume-pressure (VP) curves of initial aeration of mature (0.94-0.97 term) rabbit fetuses were compared in three groups, respectively, at 37 degrees C, with maximal inflation pressure of 25 cm H2O (P25); 22 degrees C, P25; and 22 degrees C, P30. Anesthetized fetuses were delivered through uterotomy; chest was opened; trachea of fetal pulmonary liquid (FPL)-filled lungs cannulated; and lungs inflated-deflated in 5 cm H2O, 2 min steps under continuous microscopic observation. As distending pressure was increased, FPL moved peripherally with airways inflation by free gas and with saccular recruitment by free gas and bubbles. Saccular aeration continued during initial reduction of P from Pmax. At end-deflation, air was retained in saccules virtually exclusively as bubbles. Airways inflation required less P at 37 degrees C, though airways volume (V) was the same at both temperatures. Opening P was lower, and saccular aeration was larger and more rapid at 37 degrees C. The apparently higher distensibility at 37 degrees C was most likely due to temperature effects on fluid dynamics rather than on tissue elasticity. Maximal V attained during early P reduction in all groups, was total lung capacity (TLC) at 37 degrees C and less than TLC at 22 degrees C. Air retention at end-deflation, with films of near-zero surface tension, was greatest at 37 degrees C and least at 22 degrees C, P25. Lung stability, greater at 37 degrees C than at 22 degrees C, was best discriminated when V at P0 was taken into account.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1523030 TI - Clinical observations of nebulized flunisolide in infants and young children with asthma and bronchopulmonary dysplasia. AB - Severe bronchopulmonary dysplasia (BPD) is frequently associated with asthma. The combination is often severe enough to necessitate corticosteroid therapy. There are no commercially available nebulizer solutions of corticosteroids for use in infants and young children. Seven infants and small children with very severe BPD and asthma aged 6-24 months, were treated with flunisolide, 187-250 micrograms q.i.d. in the form of nasal spray delivered by nebulizer. After treatment for 2.5 20 months, four patients showed clinical improvement, one initially improved but later deteriorated and died of cardiac failure, and two patients showed no improvement and died within 3 months. The number of days of hospitalization was significantly reduced from 8.4/month to 2.5/month (P less than 0.05). No side effects were detected and it was felt that the three patients who died, did so as a consequence of very severe BPD and its cardiac consequences. The suspension remained stable for 80 min when mixed with normal saline, cromolyn sodium, albuterol, or acetylcysteine. It is concluded that nebulized flunisolide is a potentially useful treatment for infants and young children with asthma and BPD. PMID- 1523031 TI - Diet in infancy and bronchial hyperreactivity later in childhood. AB - Sixty-seven atopy-prone children (atopic family group, AFG) and 52 children with no family history of atopy (NAFG) were followed for 10 years. During infancy, the mothers of the newborn AFG children were advised to adjust their infants' diet, with a view toward minimizing the risk of atopy, and not to keep pets. Pulmonary function tests, methacholine inhalation challenge (MIC), and skin prick tests (SPT) were done in order to evaluate the bronchial reactivity and skin reactivity in the two groups. A pathological result in MIC was found in 20 (30%) of the AFG children and in 10 (19%) of the NAFG children. Such results of MIC were more common in the children with positive SPT results than in those without (67% vs. 24%). In regard to the diet consumed in infancy, MIC was pathological in 23% of children with and in 36% without prophylactic diet in infancy. For MIC, using the new, Spira electro 2 dosimeter equipment, the sensitivity was 75% and specificity 97%, but the predictive value for diagnosing bronchial asthma was only 25%. The important advantage of our method is that the degree of bronchial reactivity can be estimated by responses to increasing provocative doses. Our observations confirm that the new method is suitable for detecting bronchial asthma in clinical practice but it seems not to be optimal for epidemiological studies. We concluded that later bronchial hyperreactivity can not be diminished by avoiding home pets or providing a hypoallergenic diet during infancy. PMID- 1523032 TI - Adenotonsillectomy for upper airway obstruction carries increased risk in children with a history of prematurity. AB - To define better the clinical presentation and perioperative outcome in children undergoing adenotonsillectomy (T&A) for relief of upper airway obstruction (UAO), we reviewed the hospital records of 60 consecutive, otherwise normal children aged 12 years or younger. Seven patients with trisomy 21, neurologic impairments, or preoperative cor-pulmonale were excluded. Intraoperative and postoperative complications were experienced by 15 (34%) and 13 (25%), respectively, of the 53 children with preoperative UAO. The most severe complications comprised pulmonary edema and prolonged postoperative oxyhemoglobin desaturation. Multivariate logistic regression analysis found a history of prematurity and/or low birth weight to be the most significant risk factors related to the occurrence of complications. Twenty-eight % of the study population had a history of prematurity and they had approximately 85% of the perioperative complications seen in children with UAO undergoing T&A. Other significant risk factors included adenoidal facies and evidence of respiratory distress at the time of surgery. It appears that T&A poses significant risk for children with UAO who were born prematurely and have evidence of abnormal facial development or respiratory distress preoperatively. PMID- 1523033 TI - Noninvasive breathing analysis: repetitive chloral hydrate in neonatal guinea pigs. AB - A noninvasive method was used to record neonatal breathing, heart rate (HR), and the electroencephalogram (EEG) in guinea pig pups. Neonates were randomly assigned at birth to chloral hydrate (CH) or placebo (PLA) treatment. Treatments were administered 30 min before each study on days 1, 3, 5, 7, 14, and 21 after birth. Animals were studied while they breathed room air followed by air with 5% CO2 and 30% O2. CH decreased breathing frequency (f) and inspiratory minute volume (VI), but not tidal volume (VT) during the first week (P less than 0.05), and reduced the rate of growth throughout the study (P less than 0.01), whereas breathing of CO2 increased f, VT, VI, HR, and the relative power in the delta frequency band of the EEG. The percent change in VI induced by CO2, however, was not affected by drug treatment. There was a significant day of life effect on all breathing parameters and HR. CH has cumulative effects on breathing and growth that should be considered when it is used as a sedative for repeated neonatal studies in guinea pigs. PMID- 1523034 TI - Effect of rapid thoracic compression on the cerebral blood flow-velocity patterns of small infants. AB - We measured the middle cerebral artery (MCA) flow-velocities of 12 small infants (mean weight, 2,882 +/- 602 g) before, during, and after the rapid thoracic compression (RTC) maneuvers of partial forced expiratory flow-volume studies. Cerebral flow-velocities were measured using transcranial Doppler ultrasonography. RTC increased MCA end diastolic flow-velocities and Pourcelot indices of all infants (P less than 0.001). These values returned to baseline immediately after the release of chest compression. We also measured the MCA flow velocities of several preterm infants during their normal daily activities. The changes in flow-velocity patterns observed during normal daily life were similar to those observed during RTC. These findings demonstrate that RTC produces real, but likely not pathologic, changes in cerebral blood flow-velocities. PMID- 1523035 TI - Snoring in French preschool children. AB - The prevalence of habitual snoring and its associations with respiratory symptoms, personal and familial risk factors, ear, nose, and throat (ENT) abnormalities, and its influence on ventilatory function were studied in a sample of 190 children aged 5 to 6 years from nine kindergartens in Nancy (northeastern France). Nineteen (10%; 95% CI 5.7-14.3%) of the children were habitual snorers; the prevalence was the same in boys and girls. In univariate analysis habitual snoring was significantly associated with a personal history of exercise-induced bronchospasm [relative risk (RR) 4.50]; a history of adenotonsillectomy (RR, 2.56); a personal history of allergy (RR, 2.83); a sibling history of atopy (RR, 2.39); and doctor-assessed tonsillar hypertrophy (RR, 2.51). These factors were entered into a logistic regression model that retained as independent determinants exercise-induced asthma, personal history of allergy, sibling history of allergy, and tonsillar hypertrophy. The height-adjusted peak expiratory flow rate was slightly, non-significantly lower in habitual snorers as compared to non-snorers (2.01 +/- 0.32 vs 2.10 +/- 0.38 L/s/m2). Due to the limited numbers in the sample, the increased risk for paternal (RR, 1.8) and maternal (RR, 1.6) smoking at home remained nonsignificant. PMID- 1523036 TI - Comparison of 2-channel and 4-channel pneumograms. AB - To determine whether the addition of air flow and O2 saturation (SaO2) channels improves sensitivity of the pneumogram in identifying cardiorespiratory pattern abnormalities, 2- and 4-channel pneumograms (PG-2 and PG-4) were simultaneously recorded in 91 consecutive infants. Forty-one infants (45%) had cardiorespiratory symptoms, and 50 were asymptomatic. Pneumograms were considered abnormal for any of the following: apnea greater than or equal to 20 seconds, heart rate less than 80 bpm for greater than 5 seconds in preterm and less than 60 bpm in full-term infants (bradycardia), shorter apnea with bradycardia or desaturation, periodic breathing greater than 7% of total sleep time in preterm and greater than 4% in full-term infants, or SaO2 less than 85% for greater than 5 seconds. Both recordings were normal in 72% of infants and abnormal in 24%. In only 4% were the PG-4 abnormal when the PG-2 were normal, in all instances due to minimum SaO2 levels of 77-84% for 5-19 seconds associated with central apnea of intermediate duration (three infants) or with mixed apnea. The difference in frequency of abnormal results between the PG-2 and PG-4 recordings was not statistically significant (X2). In conclusion, although PG-4 do increase the scope of physiological information obtained in infants with cardiorespiratory events, this short-term study does not establish whether this increase results in any long term benefits. Further, at least in this number and these types of at-risk infants, PG-4 do not improve the sensitivity of cardiorespiratory recordings for detecting abnormalities. PMID- 1523037 TI - Comparison of helium dilution and nitrogen washout measurements of functional residual capacity in infants and very young children. AB - In infants and very young children, functional residual capacity (FRC) is the lung volume most frequently measured and gas dilution techniques are most frequently used to measure FRC. We compared measurements of FRC by helium dilution (FRCHe) and nitrogen washout (FRCN2) in a lung model of known volumes (20, 40, 60, 80 mL) in 8 normal infants (NL), 8 infants with acute respiratory illness (ARI), and 7 infants with chronic lung disease (CLD). In the model lung, measurements of FRCHe had a significantly greater coefficient of variation compared to FRCN2 (6.5 vs 1.5%, P less than 0.02), but there was no such difference in the results from all infants combined (6.5 vs 6.2%). In the model lung, the difference between known volumes and the measured values was significantly different from zero only for FRCHe at 20 mL (-4.4 mL, P less than 0.02). For both FRCHe and FRCN2, the slopes of the regression equations were 0.99 and the intercepts not significantly different from zero. We conclude that techniques for measuring FRCHe and FRCN2 yield accurate, reproducible, and comparable results in normal, healthy infants and very young children, and in those with respiratory disease. PMID- 1523038 TI - Disseminated tuberculosis in a 2-month-old infant. PMID- 1523039 TI - Aplasia of respiratory tract cilia. AB - We report on ciliary aplasia of the respiratory tract, a rare disorder of the mucociliary apparatus, that is insufficiently recognized as a distinct entity. A culture method for ciliogenesis was developed by our laboratory and offers the advantage of studying cilia free of secondary changes associated with infection. Three cases of primary ciliary aplasia were documented histologically in direct biopsy specimens and also in biopsy specimens cultured specifically for ciliogenesis. Primary ciliary aplasia should be differentiated from secondary ciliary aplasia in which basal bodies are present and ciliogenesis takes place in specific culture. Only hereditary ciliary abnormalities are expressed in cell cultures. We critically review the cases of ciliary aplasia reported to date. PMID- 1523040 TI - On growth of children under inhaled steroid treatment. PMID- 1523041 TI - On air quality and prevalence of asthma. PMID- 1523042 TI - Cerebral contusional tears as a marker of child abuse--detection by cranial sonography. AB - A series of 6 infants subjected to child abuse is presented in whom contusional tears of subcortical white matter were detected during life by intracranial sonography. The sonographic appearances of this highly pathognomonic marker of shaking injury are described for the first time and their significance discussed. On the basis of our experience we suggest that high resolution cranial sonography is an extremely valuable part of the diagnostic work up in cases of suspected non accidental injury. PMID- 1523043 TI - Cerebrovascular resistive index assessed by duplex Doppler sonography and its relationship to intracranial pressure in infantile hydrocephalus. AB - Duplex Doppler sonography and direct intracranial pressure (ICP) measurement were performed on 18 patients with infantile hydrocephalus. ICP was measured through a frontal reservoir or ventricular tap using a nondisplacement pressure transducer. The Pourcelot Resistive Index, RI = (peak systolic-end diastolic)/peak systolic velocity was obtained from pulsed-wave Doppler measurements of blood flow velocity in the anterior (ACA) and/or the middle cerebral (MCA) arteries. There was a statistically significant positive correlation between ICP and RIs in the MCA and ACA. Paired RI measurements in 7 patients with raised ICP decreased significantly from a mean of 0.90 pre-tap to 0.75 post-tap. Our results suggest that the RI provides a reliable measure of cerebrovascular resistance in hydrocephalus. Duplex Doppler ultrasonography thus is a useful noninvasive means of monitoring cerebrohaemodynamic change with simultaneous imaging of ventricular size in infantile hydrocephalus. PMID- 1523044 TI - Iodine-123 scintigraphy in the evaluation of pediatric thyroid disorders: a ten year experience. AB - Few studies have been published that describe the role of scintigraphy in the evaluation of the spectrum of pediatric thyroid disorders. Between 1978 and 1987, we studied 280 children with iodine-123 (123I) scintigraphy. Clinical information and follow-up were available in 246. We analyzed the indications for referral and determined whether the information obtained with this technique was useful in subsequent management. Indications for scintigraphy included hypothyroidism, neck masses, hyperthyroidism, and miscellaneous reasons. Scintigraphy was helpful in distinguishing anatomic from functional causes of hypothyroidism. It reliably identified the location of the thyroid gland in patients with neck masses. The functional status of thyroid nodules was readily assessed and was important in directing further treatment. Scintigraphy added little to the management of children with post-irradiation hypothyroidism without a palpable nodule, patients with Hashimoto thyroiditis or Graves disease when the clinical diagnosis was straightforward. PMID- 1523045 TI - Melnick-Needles syndrome. Four new cases. AB - Melnick-Needles syndrome is a rare connective tissue disorder producing somatic abnormalities with characteristic radiographic features. There are less than 35 documented cases reported to date. We present four new cases of Melnick-Needles Syndrome, one of which is the first reported Asian-ancestry patient. Two girls are daughters of one of Needle's original patients from family #2. Two others, from unrelated non-affected families, probably represent new mutations. All have characteristic radiographic features of the disorder. PMID- 1523046 TI - Contribution of MRI in supracardiac total anomalous pulmonary venous drainage. AB - A case of supracardiac total anomalous pulmonary venous drainage (TAPVD) in an infant aged 2 1/2 months is presented. Diagnosis was established non invasively by magnetic resonance image (MRI). Not only did MRI precisely depict the anomalous venous pathway but it moreover securely excluded pulmonary venous obstruction. PMID- 1523047 TI - Plain film and CT observations in prostaglandin-induced bone changes. AB - Prostaglandin E1 intravenous infusion is used in infants with ductal-dependent congenital heart disease to maintain ductal patency and prolong life until palliative or corrective surgery is feasible. Complications of prostaglandin administration include fever, diarrhoea, hypotension, apnoea, bradycardia, pseudowidening of the cranial sutures, underossification of the calvarial bones, periostitis, and skin edema [1-3]. This paper presents dramatic plain radiographic features of prostaglandin-induced bone disease, including periosteal proliferation and the unusual bone-within-bone appearance, and provides the previously unpublished CT correlation. PMID- 1523048 TI - Oto-palato-digital syndrome type II. Report of two related cases. AB - Two cases with major features of bowed long bones, hypertelorism, mandibular hypoplasia and hand and foot abnormalities with early neonatal death due to respiratory failure are presented. The radiologic and clinical findings are in keeping with oto-palato-digital syndrome type II and differ significantly from other causes of bowed long bones such as campomelic and kyphomelic dysplasias. PMID- 1523049 TI - Bronchiolitis obliterans-organizing pneumonia (BOOP) in children with malignant disease. AB - Four patients who had completed chemotherapy for malignant disease are presented. Unexpected findings of pulmonary infiltrates on chest radiographs of two patients and solitary and/or confluent nodules on CT in all four led to open lung biopsy. Histologic diagnosis in each case was bronchiolitis obliterans-organizing pneumonia (BOOP). This usually innocuous disorder can be differentiated histologically from the more severe pure bronchiolitis obliterans and should be considered in the differential diagnosis of pulmonary lesions associated with malignant disease. PMID- 1523050 TI - The olive on end: a useful variant of the "shoulder" sign in the barium X-ray diagnosis of idiopathic hypertrophic pyloric stenosis. AB - We describe a radiographic sign of infantile hypertrophic pyloric stenosis. This sign, elicited during firm compression of the barium-coated pyloric region, is a round or avoid filling defect caused by the hypertrophied pyloric muscle protruding en face into the gastric lumen. This filling defect typically reveals a barium-containing central depression or stellate indentation, representing the proximal end of the obstructed pyloric channel. This sign, like the closely related "shoulder sign", appears to establish the diagnosis of hypertrophic pyloric stenosis without need for filling of the pyloric channel or for additional radiographic maneuvers. PMID- 1523051 TI - Fetal meconium peritonitis without sequelae. AB - Meconium peritonitis is a chemical peritonitis usually resulting from antenatal bowel rupture. Prenatal ultrasound findings include ascites, intraabdominal masses, bowel dilatation and the development of intraabdominal calcifications [1 5]. The most common bowel disorders which lead to meconium peritonitis in utero are those resulting in bowel obstruction and perforation, such as small bowel atresias, volvulus and meconium ileus [1-5]. Meconium ileus is associated with cystic fibrosis in most cases, although extraluminal abdominal calcifications are usually scarce in cases of cystic fibrosis [1, 6]. Postnatal outcome for infants with meconium peritonitis depends on the etiology for bowel rupture and underlying disease. PMID- 1523052 TI - An unusual case of meconium peritonitis associated with perforated hydrocolpos. AB - Meconium peritonitis results from intestinal wall perforation with meconium spillage into the peritoneum during intrauterine life. Anal atresia is associated with meconium peritonitis and is also associated with cloacal malformation. A female neonate presented with a distended abdomen, anal atresia, and meconium peritonitis as diagnosed by calcification in the peritoneal cavity on abdominal radiograph. Sonography and cystography demonstrated a cloacal malformation with perforation of the hydrocolpos and resultant spillage of meconium into the peritoneum. There was no evidence of further perforation of bowel at surgery. This unusual case of meconium peritonitis is reported. PMID- 1523053 TI - Focal fatty infiltration of the liver in a healthy child. AB - Fatty infiltration of the liver may occur in healthy children. The ultrasonographic, CT, and MRI findings are identical to those already described in the adult population. PMID- 1523054 TI - Intrahepatic biliary stones in children. AB - Intrahepatic biliary stones in seven non-Oriental patients were studied in all by sonography, in four patients by computed tomography and in four patients by percutaneous transhepatic cholangiography. For patients had extrahepatic biliary atresia treated with portoenterostomies, one patient had undergone partial liver transplantation and of the remaining two, one had cystic fibrosis and the other immunodeficiency syndrome. All sonograms were abnormal and showed echogenic foci within the liver, with or without associated signs of biliary tract dilatation. CT confirmed the biliary tract dilatation yet calculi were identified in one patient only. PTC was particularly helpful in the patient with immunodeficiency in whom features typical of sclerosing cholangitis were found. This report emphasizes the variable radiological appearance of bile stones which to our knowledge have rarely been described in children with entities other than Oriental cholangitis. PMID- 1523055 TI - Fluoroscopic placement of jejunal feeding tubes. AB - Over a two-and-one-half year period, 50 children underwent placements of jejunal tubes through a nasal route (NJ, n = 47) or through an existing gastrostomy site (GJ, n = 119). There were four attempted placements (98% success rate). The NJ tubes remained in place an average of 13 days, and the GJ tubes remained in place an average of 37 days. Fluoroscopic time for placement of an NJ tube averaged 6 min (29 cases), and for a GJ tube 8 minutes (91 cases). In spite of the limited retention time, fluoroscopic time, and availability of alternative methods, fluoroscopically placed jejunal feeding tubes are still playing an active role in this institution. PMID- 1523056 TI - Paediatric myelography with iohexol. AB - 32 paediatric patients requiring myelography were studied with iohexol 210 mgI/ml (n = 15) and iohexol 180 mgI/ml (n = 17). Visualization was good or excellent in over 90% of the group receiving the higher concentration and in over 83% of the lower. There were no side effects in either group and vital signs were not significantly altered during the procedure. In the majority of patients (14/18) who had CT, additional diagnostic information was obtained. Iohexol 180 mgI/ml is preferred for routine use, but 210 mgI/ml may give superior visualization with no apparent added risk. Procedural technique and good communication with the patients and their families may have contributed to the absence of side effects. PMID- 1523057 TI - Multiple myeloma in an adolescent. AB - The radiographic findings of a 15-year-old Brazilian male with diagnosis of multiple myeloma are described. He presented with claudication and recent onset of tender painful swelling of the right mid leg. Radiographs showed wide spread "soap bubble" lesions of the skull, long bones, spine, pelvis, ribs, shoulders, and clavicles. The diagnosis was confirmed by the presence of a plasmacytoma on tissue biopsy (femur), serum IgG gammopathy and Bence-Jones proteinuria. PMID- 1523058 TI - Sonography of intrascrotal hematomas simulating testicular rupture in adolescents. AB - Four cases of intrascrotal hematoma simulating testicular rupture were noted in teenagers. Careful sonographic technique allowed for the discovery of the normal testicle in a more peripheral location in the scrotum. Duplex doppler aided in confirming a normal testis in one case. PMID- 1523059 TI - Bubble gum simulating abdominal calcifications. AB - CT examination of the abdomens of two children demonstrated sites of high attenuation in the stomach, which were revealed to be bubble gum. Investigation of the CT appearance of samples of chewing gum showed that it consistently has high attenuation (178-345 HU). The attenuation of gum base, which contains calcium carbonate, was 476 HU. In addition, examination of a volunteer who had swallowed bubble gum confirmed the CT appearance. PMID- 1523060 TI - Diagnosis of peanut inhalation by MRI. AB - A peanut is a commonly inhaled foreign body during childhood. Some cases are difficult to diagnose especially in cases without a clear history of inhalation. We describe a 16-month-old boy presenting with stridor and fever. The chest x-ray suggested inhalation of a foreign body but there was no history of this. A high spot on a T1-weighted chest MRI was due to a peanut which was seen to have moved from the right main bronchus to the left inferior bronchus, between the two MRI studies. MRI can provide information on position and size of the peanut, the conditions of the surrounding tissues and may be also useful in treatment. We consider MRI to be a valuable new method for the diagnosis of peanut inhalation. PMID- 1523061 TI - MR demonstrates cartilaginous megaepiphyses of the hips in Kniest dysplasia of the young child. AB - MR imaging of a 2-year-old girl with Kniest dysplasia revealed abnormally large cartilaginous femoral heads. Although ossification of the femoral head is delayed in Kniest dysplasia, it is nonetheless also a megaepiphyseal growth center with respect to the cartilage model. PMID- 1523062 TI - Extracorporeal shock wave lithotripsy and xanthine calculi in Lesch-Nyhan syndrome. AB - We report a case of Lesch-Nyhan syndrome (LNS) with urinary xanthine calculi. At eight years of age calculi in the renal pelvis were successfully disintegrated by extracorporeal shock wave lithotripsy (ESWL) without any complications. Follow-up sonography is very useful for management of patients with LNS, particularly when they are on allopurinol therapy. PMID- 1523063 TI - Isolated intrathoracic spleen presenting as an enlarging chest mass. CT and MRI findings. AB - We present the first reported case of an isolated intrathoracic spleen. This presented as an enlarging chest mass in a 6-month-old infant. The lack of symptoms and absence of herniated bowel caused an interesting diagnostic problem which was elegantly solved by a combination of imaging modalities. PMID- 1523064 TI - Cystic mesenchymal hamartoma of the liver. AB - Two cases of multicystic mesenchymal hamartoma of the liver in children are described. In both cases noninvasive imaging techniques (ultrasound, CT or MR, radionuclide scan) showed a bulky cystic mass suggesting a correct preoperative diagnosis, while selective arteriography defined the operability of the tumor. PMID- 1523065 TI - Intraabdominal calcifications in the newborn: an unusual case with anorectal malformation and other anomalies. AB - Intraabdominal calcifications are an unusual radiographic finding in the newborn and can easily be misinterpreted as meconium peritonitis. The authors refer to a patient with anorectal malformation (ARM), intraluminal calcifications and other anomalies. Careful differentiation of the type of intraabdominal calcifications can suggest the possibility of other initially unsuspected anomalies. PMID- 1523066 TI - Bilateral subdural effusion (hygromas) in non-immune hydrops fetalis. AB - In addition to body edema fluid accumulation in serous cavities is a component of non-immune hydrops fetalis. A case with bilateral symmetrical subdural effusion is reported. Fluid accumulation in this space appears to be a part of this entity. PMID- 1523067 TI - Sonographic findings in spontaneous renal transplant rupture. AB - A post-transplant kidney became acutely swollen during a rejection episode. The hemoglobin level and pulsitility index fell. Sonographic examination demonstrated extrarenal and subcapsular collections due to spontaneous renal transplant rupture. PMID- 1523068 TI - Maternal renal insufficiency: a cause of congenital rickets and secondary hyperparathyroidism. PMID- 1523069 TI - Immunization with oligosaccharide conjugate Haemophilus influenzae type b (HbOC) vaccine on a large health maintenance organization population: extended follow-up and impact on Haemophilus influenzae disease epidemiology. The Kaiser Permanente Pediatric Vaccine Study Group. AB - Between February, 1988, and June, 1990, the safety, immunogenicity and efficacy of the HbOC (oligosaccharide conjugate Haemophilus influenza type b) vaccine was evaluated in a prelicensure trial performed in a study population of 61,080 children within the Northern California Kaiser Permanente Medical Care Program. In this evaluation the HbOC vaccine was found to be safe, immunogenic and efficacious in infancy. Since licensure an estimated 162,000 additional doses of HbOC vaccine have been given to 75,000 additional children. In addition to reporting on extended follow-up of this population, this publication reports on the impact of immunizing a high proportion of the Northern California Kaiser Permanente Medical Care Program population in infancy and early childhood on the epidemiology of invasive disease caused by H. influenzae type b (Hib) and invasive disease caused by non-type b H. influenzae. As of January 31, 1992, six cases of Hib invasive disease have been identified in vaccinated children. Of these five occurred in children who had received only one dose of vaccine in infancy. One case of Hib meningitis occurred in a 3 1/2-year-old child who had received doses of HbOC at 2, 4 and 6 months of age but no further doses of any Hib vaccines. During 1991 a total of three cases of invasive disease caused by Hib were observed in children younger than 18 months of age within the Northern California Kaiser Permanente Medical Care Program. This represents a 94% reduction in disease incidence in this age group from that observed in the years 1984 to 1987.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1523070 TI - Respiratory syncytial virus: a comparison of diagnostic modalities. AB - This study compared prospectively viral culture for respiratory syncytial virus (RSV) with three rapid RSV antigen detection tests: RSV EIA and TestPack RSV (TP), and Directigen RSV (DIR). Additionally two methods of specimen collection were compared: nasopharyngeal rub (RUB) and nasopharyngeal wash (WASH). True positives were defined as positive RSV viral culture or at least two positive antigen tests. One hundred ninety-eight WASH specimens obtained from children 3 years of age or younger during the 1991 RSV winter epidemic were tested for RSV antigen. Sensitivity and specificity of WASH specimens were 59.5 and 100% (culture), 86.2 and 98.2% (RSV EIA), 91 and 96.3% (TP) and 83.5 and 94.3% (DIR). Concurrently obtained RUB samples from 124 children were tested by TP and/or DIR. Sensitivity of RUB specimens was significantly lower than that of WASH specimens; 64.9% (TP) and 43.6 (DIR). These easy to perform, rapid RSV antigen tests for WASH specimens provide timely diagnosis thereby facilitating management decisions and isolation efforts. PMID- 1523071 TI - Successful intervention in a group A meningococcal outbreak in Auckland, New Zealand. AB - During two consecutive winter seasons (1985 and 1986) Auckland, New Zealand, experienced epidemic rates of Group A meningococcal disease, a pattern not previously recognized in New Zealand. The overall rate was 8.3/100,000/year. The highest annual rate (64.7) occurred in children 0 to 23 months of age. A city wide vaccine campaign commencing in May, 1987, was conducted over 6 weeks among children 3 months to 13 years of age with special emphasis on reaching populations at highest risk (Maori and Pacific Island Polynesian children in certain geographic regions of Auckland). Children from 2 to 13 years of age received a single dose of monovalent Group A meningococcal vaccine. Children ages 3 to 23 months received two doses at least 1 month apart. Overall approximately 130,000 doses were delivered; coverage was approximately 90% in the single dose target group. Among the younger children approximately 89% received the primary dose. Only approximately 26% received the recommended "booster" dose. After 2 1/2 years of active surveillance (1987 to 1989) there were no cases of invasive Group A meningococcal disease in children appropriately vaccinated for age. In contrast to this 100% efficacy the efficacy of a single dose of monovalent Group A meningococcal vaccine to prevent illness in the youngest children during the 1987 epidemic period was 52% (95% confidence interval (-330%, 95%)) falling to 16% (95% confidence interval, (-538%, 90%)) after 1 year. Four cases that occurred in infants 3 to 7 weeks before the scheduled "booster" campaign supports limited true efficacy. However, the prescribed 1 to 3-month interval between the two doses in infants may be too long.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1523072 TI - Virulence properties of Enterobacteriaceae isolated from the small intestine of children with diarrhea. AB - Enterobacteriaceae isolated from the duodena of Peruvian children with persistent diarrhea (PD) have been examined for virulence factors and compared with Enterobacteriaceae isolated from children with acute diarrhea, those convalescent from PD and diarrhea-free controls. Escherichia coli were isolated from 42 of 186 (23%) of the aspirates. All 11 children with PD in whom multiple E. coli colonies were examined were colonized by a single serotype. DNA probes identified enterotoxigenic E. coli in 2 of 89 (2.2%) PD aspirates and 2 of 38 (5.3%) acute diarrhea aspirates and enteroaggregative E. coli in one PD and one control aspirate. Strains positive with the enteropathogenic E. coli adherence factor probe were identified from 2 of 89 (2.2%) patients with PD and 1 of 34 (2.9%) controls. A subset of 12 E. coli strains failed to show adhesion to human duodenal enterocytes although 5 of 9 showed sparse but polar attachment to ileal cells from a child with short bowel syndrome and PD. Three of 10 Enterobacteriaceae (two E. coli, one Klebsiella species) caused diarrhea in the reversible ileal tie adult rabbit model. Colonization with virulent Enterobactericeae did not explain the majority of episodes of PD. Examination of these duodenal bacteria in the rabbit model revealed some that caused diarrhea but were not recognized pathogens. PMID- 1523073 TI - Natural history of human immunodeficiency virus type 1 infection in children: prognostic value of laboratory tests on the bimodal progression of the disease. AB - This study analyzes the correlation of basic laboratory test results with clinical outcome in 94 children with perinatally acquired human immunodeficiency virus 1 infection who did not receive zidovudine during the study period of 1983 to 1988. Two life-threatening conditions highly correlated with survival, opportunistic infection and severe encephalopathy, were the end points of the study. At a median age of 25 months 30 (32%) of the 94 children had developed such conditions (Group I), and their survival at 3 years of age was 48% (95% confidence interval, 24 to 72%), contrasting with the 97% survival rate (95% confidence interval, 94 to 100%) of the remaining 64 (68%) children who had not developed such conditions by age 25 months. (Group II). Compared with children in Group II, children with life-threatening complications were more likely at the onset of symptoms to be younger and have a lower CD4 count, an impaired in vitro lymphocytic proliferation and a lack of p18 or p25 antibodies in the Western blot profile and, during the progression of the disease, a negative slope of the subsequent CD4 counts. These results highlight the need for an early diagnosis of the human immunodeficiency virus 1 infection in children and demonstrate that it is possible to determine the prognosis of their disease as early as in the first year of life. PMID- 1523074 TI - Diagnosis of human immunodeficiency virus infection by enzyme-linked immunospot assays in a prospectively followed cohort of infants of human immunodeficiency virus-seropositive women. AB - The enzyme-linked immunospot (ELISPOT), a method for quantifying specific and total antibody-secreting cells, was used for the diagnosis of human immunodeficiency virus (HIV) infection in a prospectively followed cohort of infants born to HIV-infected women. From July 1, 1987, to June 1, 1990, 127 infants with known HIV infection status were studied. Seventeen of 22 HIV infected infants had specific HIV-specific antibody-secreting cells (ASC). Among the infected infants rates of ASC positivity increased during the first year of life, from 25% in the first 5 days of life to 78% after 6 months. Two of the five ASC-negative infected infants were further characterized as hypo- or dysgammaglobulinemic by an adjunct ELISPOT assay for total immunoglobulin secreting cells. Excluding hypo- or dysgammaglobulinemic infants from the analysis, the rate of ASC positivity among infected infants was 85% (17 of 20) after the age of 6 months. None of the 95 uninfected infants had a positive ELISPOT assay, including 55 who were tested in the first 3 months of life. Thus in this series the specificity was 100%. ELISPOT methodology can be a useful technique for the diagnosis of HIV infection in infants of HIV-seropositive mothers. PMID- 1523075 TI - Lymphocyte subsets in children younger than 2 years old: normal values in a population at risk for human immunodeficiency virus infection and diagnostic and prognostic application to infected children. AB - Data were collected prospectively from 116 children younger than 2 years old who were seen at the Duke Pediatric AIDS Clinical Trials Unit for known human immunodeficiency virus seropositivity. Forty-six (40%) of these children were human immunodeficiency virus-infected and 70 were not infected. Using 3-month blocks, 10th, 50th and 90th percentiles were calculated for the CD4+ and CD8+ cell counts, percentage of lymphocytes positive for CD4 and CD8 and T4:T8 ratios. Results from the infected and uninfected children were compared. By 3 to 6 months of age the infected patients had significantly lower CD4+ counts, percentage CD4+ cells and T4:T8 ratios, whereas the percentage of CD8+ lymphocytes was significantly higher. Absolute CD8+ counts were approximately the same in infected and uninfected children through age 2 years. Most infected children had one or more abnormal lymphocyte subset results (less than the 10th percentile for uninfected patients) by age 2: 83% had an abnormal CD4+ percentage; 78% had an abnormal T4:T8 ratio; and 67% had an abnormal CD4+ count. All 13 children who had an opportunistic infection (at any age) had an abnormal CD4+ percentage before age 2 years, and 12 of 13 had a low absolute CD4+ count or T4:T8 ratio. Among patients who died 10 of 11 had 1 or more low CD4+ count, 9 of 11 had an abnormal CD4+ percentage and 8 of 11 an abnormal T4/T8 ratio. PMID- 1523076 TI - Ceftibuten and trimethoprim-sulfamethoxazole for treatment of Shigella and enteroinvasive Escherichia coli disease. AB - In a prospective randomized study at two clinical sites, ceftibuten was compared with trimethoprim-sulfamethoxazole (TMP-SMX), both given orally for a period of 5 days, for the treatment of dysentery. Twenty-two children were found to have bacillary dysentery caused by Shigella and/or enteroinvasive Escherichia coli. All organisms isolated were susceptible to ceftibuten; 6 of 20 Shigella strains and 4 of 5 enteroinvasive E. coli were resistant to TMP-SMX. The diarrhea persisted for a mean (+/- SD) period of 2.4 +/- 1.4 days in the ceftibuten treated patients vs. 3.4 +/- 1.7 days in the TMP-SMX-treated patients. The duration of fever was similar for both treatment groups. Patients treated with ceftibuten or TMP-SMX had equivalent clinical responses unless the pathogen was found to be TMP-SMX-resistant. Those who were randomized to receive TMP-SMX but who were eventually found to have TMP-SMX-resistant organisms had significantly more stools at days 3, 4 and 5 (P less than 0.02 to less than 0.00006) with more watery consistency for these days (P less than 0.02 to less than 0.005) compared to patients treated with ceftibuten. No clinical relapses were reported and no drug-related side effects were observed. We conclude that ceftibuten is at least as effective as TMP-SMX in the treatment of diarrhea caused by Shigella and enteroinvasive E. coli in children. PMID- 1523077 TI - Colonizing and invasive strains of Streptococcus pneumoniae in Uruguayan children: type distribution and patterns of antibiotic resistance. AB - For the first time in Uruguay the frequency of moderate to heavy colonization of the upper respiratory tract by Streptococcus pneumoniae was investigated in children with acute respiratory infections (n = 717) and in healthy controls (n = 564). Serotypes of S. pneumoniae were identified as colonizing and invasive strains and their susceptibility to antibiotics was determined. Semiquantitative cultures of nasopharyngeal aspirates yielded 42.1% of positives in ambulatory patients and 15.2% in controls. Throat swabs from hospitalized children and matched controls revealed, respectively, 18.4 and 11.5% colonization. Different sampling and culture procedures were evaluated. Seasonal variations in colonization were also detected. Geographic variations in serotype frequency and distribution were assessed. Serotype 14 was predominant among invasive and colonizing strains in patients. Ten serotypes, included in the 23-valent S. pneumoniae vaccine, were not detected. Intermediate resistance to penicillin was seldom observed, but 37.2% of the invasive strains were resistant to cotrimoxazole, indicating the need for a permanent surveillance of isolates to antibiotic susceptibility. PMID- 1523078 TI - Epidemiology of pertussis in a developed country with low vaccination coverage: the Italian experience. AB - In Italy pertussis vaccination is optional. Fewer than 40% of children younger than 5 years of age are vaccinated, and pertussis remains a common childhood disease. We use data from a variety of sources to examine trends and characteristics of Italian children with pertussis and reasons behind the low vaccine coverage. Approximately 25% of Italian children have experienced clinical pertussis by their fifth birthday. The disease is most severe in those less than 1 year of age; in this group an estimated 1 in 14 cases are hospitalized and 1 in 850 die. The incidence appears to be increasing in the 1- to 4-year age group despite increased vaccination coverage. The low vaccine coverage appears to be caused by the ambivalence of the Italian pediatric community about the vaccine rather than parental concerns about vaccine safety. Legislation is being considered to make pertussis vaccination mandatory. PMID- 1523079 TI - Cephalosporin treatment failure in penicillin- and cephalosporin-resistant Streptococcus pneumoniae meningitis. PMID- 1523080 TI - Congenital brucellosis. PMID- 1523081 TI - Recurrent aseptic meningitis secondary to an intracranial cyst: a case report and review of clinical features and imaging modalities. PMID- 1523082 TI - Characteristics of human immunodeficiency virus-associated mortality in pediatric patients with vertically transmitted infection. PMID- 1523084 TI - Microbiology of subphrenic abscesses in children. PMID- 1523083 TI - Natural maternal and cord serum antibodies to pneumococcal serotypes 6A, 14, 19F and 23F polysaccharides. PMID- 1523085 TI - Incest and Pneumocystis carinii pneumonia in a twelve-year-old girl: a case for early human immunodeficiency virus testing in sexually abused children. PMID- 1523086 TI - Transmission of human immunodeficiency virus infection from a newly infected mother to her two-year-old child by breast-feeding. PMID- 1523087 TI - Tuberculosis in children with acquired immunodeficiency syndrome. PMID- 1523088 TI - Prophylactic use of trimethoprim-sulfamethoxazole in children with recurrent otitis media. PMID- 1523090 TI - Jubilee issue dedicated to Professor Jacques Caen in honour of his 65th birthday. PMID- 1523089 TI - Appropriate technique for obtaining urine in a newborn. PMID- 1523091 TI - The assembly and structure of the fibrin clot. AB - This review summarizes our current understanding of the structure of the fibrinogen molecule, its conversion to fibrin, and the main features of fibrin clot assembly and crosslinking. Several major aspects of fibrin matrix assembly and crosslinking are newly discovered, and differ significantly from more traditional views of fibrin structure. The new information that I have summarized will be of importance for correctly understanding the role that fibrin plays in the hemostatic process, and for learning how the structure of the fibrin clot network contributes to its strength, elasticity, interactions with cells, tissue matrix, and its susceptibility to fibrinolysis. PMID- 1523092 TI - Further evidence that heparin-dependent thrombocytopenia may result from Fc receptor-mediated interactions. AB - Heparin-dependent thrombocytopenia (HDT) and associated thrombotic complications, are thought to be linked to the appearance of anti-platelet antibodies. Attempts were made to characterize the antibodies in the sera from 10 such patients. Western blotting against platelet antigens was inconclusive, often revealing multiple bands but with considerable variability from patient to patient. An often seen band of approximately 83 kDa was also given by some nonimmune sera and the antigen appeared to be predominantly intracellular in origin. Antibodies to major membrane glycoproteins were not readily apparent. This was confirmed by the MAIPA ("Monoclonal Antibody Immobilization of Platelet Antigens") test, performed to detect antibodies to GP Ib-IX and GP IIb-IIIa. Only one weak activity to GP Ib IX and one weak activity to GP IIb-IIIa were detected. In contrast, an antibody to the PlA1 alloantigen was readily detected in the serum of an additional patient. The ability of HDT serum to induce the aggregation of control platelets was studied in detail. Aggregation was inhibited by EDU-3, a monoclonal antibody to GP IIb-IIIa complexes, and by the synthetic peptide RGDS, suggesting an involvement of the same pathway as used by physiologic agonists. However, in agreement with Chong et al (Thromb Res 55:291, 1989), we observed that aggregation was inhibited by rabbit IgG, suggesting that it was Fc-receptor mediated. Interestingly, 2E1, a monoclonal antibody to the Fc gamma RII receptor, induced platelet aggregation with a lag phase, a characteristic of HD antibodies. Nonetheless, for different donors, there was no correlation between the length of the lag phase induced by 2E1 and HD antibodies. Fc-receptor blockade should be considered as a means for diminishing the clinical complications of HDT. PMID- 1523093 TI - Differential effects of extra- and intracellular calcium chelation on human platelet function and glycoprotein IIb-IIIa complex stability. AB - The presence of extracellular ionized calcium (Ca2+) is important to support the aggregation of human blood platelets and for the stability of the platelet fibrinogen receptor, the glycoprotein (GP) IIb-IIIa complex. This study was performed in order to determine the effects of intracellular calcium chelation on human platelet functions, on the expression of the fibrinogen receptor and on the stability of the GP IIb-IIIa complex. Intracellular Ca2+ of intact human platelets was extensively chelated by incorporation of high amounts (14-50 mmol/L) of the specific Ca2+ chelator quin2 after incubation of platelets with its lipophilic acetomethoxylester form (quin2-AM). We have investigated the effects of intracellular Ca2+ chelation with quin2 on platelet aggregation and fibrinogen binding induced by ADP and human alpha-thrombin and on the stability of the GP IIb-IIIa complex studied by crossed immunoelectrophoresis of Triton X 100 platelet lysates. The results were compared with control experiments performed with intact platelets treated with the impermeant Ca2+ chelator quin2 and with EDTA or EGTA. This study shows that high intracellular concentration of quin2 inhibits human platelet aggregation and fibrinogen binding but does not induce the dissociation of the GP IIb-IIIa complex. This study adds evidence for the role of external Ca2+ to maintain the integrity of a non-dissociated GP IIb IIIa complex and suggests that intracellular Ca2+ is not involved in the stabilization of the GP IIb-IIIa complex. PMID- 1523094 TI - Characterization of a thrombopathy (type delta storage pool disease) affecting a pig colony. AB - An autosomal recessive thrombopathy in pigs is described and characterized functionally, morphologically and biochemically. The affected pigs have a severe bleeding diathesis and a markedly prolonged bleeding time but normal plasma and platelet von Willebrand factor (vWF) levels. Electron micrographs and fluorescence microscopy with mepacrine reveal reduced numbers of dense granules in platelets as compared to normals. This thrombopathy is a pure delta storage pool disease (SPD), as evidenced: a) biochemically by platelet serotonin content and metabolism and by comparative ATP/ADP content and secretion; b) functionally by reduced aggregability to low concentrations of convulxin and collagen but normal aggregability to other agents and normal synthesis of thromboxane B2. The affection was first discovered in a colony of von Willebrand's disease (vWD) pigs, but is biologically and genetically distinct. It is possible to completely separate the SPD from the vWD, although originally animals could be affected by both vWD and SPD. Normal plasma and platelet alpha granule content of vWF are found in diseased animals. An intermediate disorder is also detected in animals not severely affected, which may represent the heterozygous state. PMID- 1523095 TI - Inexpensive manual synthesis of antithrombotic peptides. AB - We describe a simple, improved method of manual synthesis of biologically active, antithrombotic peptides. The prototype peptide KYGRGDS is an effective inhibitor of platelet aggregation in vivo. This Fmoc-based method can be implemented by the research lab that would otherwise not have access to this technology because of safety or financial concerns. This method facilitates the synthesis of large numbers of peptides in quantities of 25 to 50 mg. Fmoc manual synthesis produces high quality peptides in fewer working days than current automated approaches. PMID- 1523096 TI - Protein C and hypertension. AB - Protein C antigen and amidolytic activity were assayed in 38 patients with essential hypertension at the first stage of disease. As compared to 20 normal healthy blood donors no abnormality was found. PMID- 1523097 TI - Plaque fissure: the link between atherosclerosis and thrombosis. AB - The immediate cause of arterial, predominantly coronary thrombosis is almost always cracking or fissuring of the cap of an atheromatous plaque. This exposes collagen and lipids to the flowing blood and thereby initiates thrombotic platelet aggregation, almost immediately followed by coagulation. The thrombi tend to extend into the arterial lumen, causing obstruction to blood flow and clinical symptoms and signs. Evidence for this sequence of events comes, inter alia, from angiograms of patients with unstable angina and developing myocardial infarction. Direct angioscopy in life is also visualising mural thrombi over fissured plaques in atheromatous coronary arteries. We are investigating the initial development of atheromatous plaques liable to fissuring. The cap over such plaques covers a "lipid pool". We have discovered that one factor promoting the uptake of lipid, in the form of plasma low-density lipoprotein, is the concentration of circulating catecholamines (Cardona-Sanclemente LE, Gorog P, Born GVR (1992) J Physiol London, in press). We are also investigating the immediate cause(s) of plaque fissure. We have evidence for a complex interaction of different determinants, including the concentration of macrophages, presumably as foam cells, in the plaque caps (Lendon CL, Davies MJ, Born BVR, Richardson PD (1991) Atherosclerosis 87: 87). PMID- 1523098 TI - Neutralization of lupus anticoagulant activity by human immunoglobulin "in vitro". AB - We studied the in vitro effect of human intravenous immunoglobulin (IVIg) on the lupus anticoagulant (LA) activity present in sera of 11 patients. LA potency was determined in all the cases and a fixed dilution of each serum was chosen to perform the dose-dependent neutralization experiments. For each patient, the dilute serum was incubated for 3 h at 37 degrees C with phosphate buffer saline (PBS) alone or containing IVIg at final concentrations of 0 to 50 mg/ml. Aliquots of the incubation mixtures were added to equal volumes of normal plasma and APTTs were performed. IVIg partially neutralized the LA activity present in 10 out of 11 patients sera. These neutralizations showed an IVIg dose-dependent behaviour. Statistically significant neutralizations were observed at least at one molar ratio (MR = [IVIg]/patient's [IgG] or [IgM]). In every case, a particular MR was found in which the neutralization was maximal (N%max). The N%max ranged from 33.6% to 79.5%. Eight patients showed maximal LA neutralization at MR ranging from 8.9 to 56.8. In one patient with drug-induced LA and another exhibiting LA cofactor effect, MRs were more elevated. We found poor negative correlation between N%max and LA potency (r = -0.46) or N%max and MR of N%max (r = 0.47), although no statistic significance was reached. However, there was good agreement between LA potency and MR of N%max (r = 0.98, p less than 0.001). We have shown that IVIg may neutralize LA activity in vitro. In view of these results, we believe that IVIg should be considered as an alternative therapy in patients with LA-related clinical complications. PMID- 1523099 TI - Influence of aging on the activity of the hemostatic system: prothrombin fragment 1+2, thrombin-antithrombin III complexes and D-dimers in 80 healthy subjects with age ranging from 20 to 94 years. AB - To determine the influence of aging on the activity of the hemostatic system, we measured the plasma concentration of prothrombin fragments 1+2 (F 1+2), thrombin antithrombin III complexes (TAT) and fibrin degradation fragments D-dimers (D-D) in 80 healthy subjects with age ranging between 20 and 94 years. All subjects were free of acute or chronic diseases. The three markers (semi-log scale) were positively correlated with age (r greater than 0.7, p less than 0.01). Mean plasma levels of F 1+2, TAT and D-D were two- to five-fold higher in subjects with age greater than or equal to 60 as compared to those less than 60 years (n = 40 in both groups). In these two groups, normal values for F 1+2, TAT and D-D ranged from 0.3-1.2 vs 0.7-2.4 nmol/l, 1.4-2.6 vs 1.9-6.4 micrograms/l and 33-433 vs 312-1180 micrograms/l, respectively. Sex did not influence the results. We conclude that the activity of the hemostatic system is markedly age-dependent, and that elderly subjects display a biological picture of "prethrombotic" state. In addition, for a right clinical use of these three markers, age should be taken into account when normal range is to be established. PMID- 1523100 TI - Impaired fibrinolytic response to DDAVP in patients with von Willebrand's disease. AB - The fibrinolytic response after infusion of 1-deamino-8-d-arginine vasopressin (DDAVP) was examined in 4 patients with the severe form and 17 patients with the moderate form of Von Willebrand's disease (VWd) and compared to that of 9 normal subjects. Tissue plasminogen activator (t-PA) antigen (Ag) and activity and tissue plasminogen activator inhibitor (PAI) were measured before and after DDAVP. t-PA Ag was found to be significantly higher before DDAVP in patients than in controls. No release of t-PA Ag was observed in the 4 patients with the severe form of VWd but increased release was observed in patients with moderate forms. However, t-PA released into the circulation in these 17 patients had a lower functional activity as compared to that of normal subjects. PAI was significantly lower in patients before DDAVP than in normal subjects and the decrease in PAI after DDAVP was significantly less in patients than in controls. It is concluded from this study that patients with VWd have an abnormal fibrinolytic response after stimulation regardless of the severity of the disease. Furthermore, the results suggest either that patients with VWd have a double defect in VWF and tissue plasminogen activator or that the primary deficiency of VWF influences the synthesis and/or release of t-PA by endothelial cells. PMID- 1523101 TI - Polymorphism of platelet glycoprotein Ib associated with variability of the 85 kDa macroglycopeptide region. AB - Polymorphism of platelet membrane glycoprotein Ib (GP Ib) has been described in both normal and functionally abnormal platelets. In this report we have investigated the polymorphism in one Australian Caucasian family with normal platelet function in which the following phenotypes were found: father, BC; mother, CD; son, BC; and daughter, BD; thus establishing a genetic basis for this phenomenon. The daughter's phenotype BD is highly distinctive due to the double band pattern obtained by gel analysis. Platelets from the daughter were digested with either trypsin or elastase and the GP Ib cleavage products were examined by immunoprecipitation with anti-GP Ib-IX complex monoclonal antibodies against each of the major tryptic domains. On the basis of these studies, we have determined that the GPIb polymorphism in this family resides in the 85-kDa, macroglycopeptide region of the alpha-chain of GP Ib and not in either the 45 kDa, N-terminal region of GP Ib alpha or the membrane-associated region of the complex. PMID- 1523102 TI - A directed search for mutations in hemophilia A using restriction enzyme analysis and denaturing gradient gel electrophoresis. A study of seven exons in the factor VIII gene of 170 cases. AB - Genomic DNA from 170 unrelated hemophilia A patients was examined for gene defects in the coding region of the Factor VIII gene. Exons 18, 22-24 and 26 contain a CGA codon for arginine within the recognition sequence for the restriction enzyme Taq I. These five sites were amplified by the polymerase chain reaction and tested for abnormal Taq I restriction patterns. In five cases, the enzyme Taq I failed to digest the amplified fragments. Direct sequencing of the amplified products demonstrated a C to T transition in the coding strand of exons 18, 22 and 24 in three severe hemophilia A patients resulting in TGA termination codons. Two patients showed G to A transition in exons 24 and 26 reflecting a C to T transition in the non-coding strand substituting a glutamine for an arginine. Three deletions involving exon 26 and one exons 23-26 were found in severe hemophiliac patients. In contrast, exons 23 and 24 failed to amplify in one patient with a moderate form of the disease suggesting an in-frame splicing of exons 22 and 25. Exon 8 and the 3' end of exon 14 were analyzed by denaturing gradient gel electrophoresis (DGGE). Two patients with a moderate form of the disease demonstrated an abnormal electrophoretic pattern in exon 8 and sequencing demonstrated missense mutations at codon 372 for arginine within a thrombin activation site. One missense mutation was a C to T transition substituting cysteine for arginine and the other was an infrequent G to C transversion at an adjacent nucleotide changing the same arginine to proline.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1523103 TI - Immunological study of platelet glycoproteins and alloantigens in families of patients with Glanzmann's thrombasthenia. AB - To explore the genetic transmission of Glanzmann's thrombasthenia (GT) we conducted a study of platelet glycoproteins and antigens using monoclonal and polyclonal antibodies and cytofluorometry. Twenty-one members of 4 different families in which at least one member was affected with GT were explored. The reactivity with AP2 (anti-GP IIb-IIIa complex, CD41a), AP3 (anti-GP IIIa) and antibodies against HPA-1a (PLA1) and HPA-3a (Leka) was lower than 5% in the platelets of 5 patients with GT type I. Nine obligatory carriers of the GT trait were tested by the same technique. The mean values of reactivity expressed as per cent of normal with AP2 (anti-CD41a) and AP3 (anti-GPIIIa) were 58.3 +/- 3.6% and 58.6 +/- 3.6% respectively, while the frequencies of HPA-1a (PLA1) and HPA-3a (Leka) negativity were 0/9 and 4/9 respectively. When both antigens were expressed they were detected at reduced levels. These results indicate that cytofluorometry is a simple technique for GT detection, but this method would nevertheless not appear to be sufficiently accurate to identify obligatory carriers in a general population. PMID- 1523104 TI - Platelet plasma membrane is equally distributed between surface and osmotically evaginable surface-connecting membrane, independent of size, subpopulation or species. AB - Osmotic swelling can double the external plasma membrane surface area of normal human platelets. The surface-connected open canalicular system (SCCS) has been proposed as the major source for this additional membrane. As bovine (B) platelets have been reported to lack SCCS, we compared osmotic swelling for B and human (H) cells. Addition of water to platelet-rich-plasma (10-90% v/v) caused sequential shape change and osmotic spherocyte (OS) formation, analyzed for size and surface area changes from time-dependent phase-contrast videomicroscopic images. Selected samples were fixed and stained with tannic acid prior to osmic acid fixation for visualization of open SCCS by transmission electron microscopy. Bovine platelets required 3-4x less water dilution of PRP than human platelets, with significant OS forming at 20% water addition. Continued water dilution converted 50% of platelets to OS, with maximally stable swelling and no significant lysis for bovine OS up to 60% dilution. Electron micrographs of unactivated discocytes (D) and of optimally-swollen OS showed open SCCS in human D not detectable in any of the swollen platelets, though granules, mitochondria and a small number of vesicles and vacuoles persisted. No evidence for any open SCCS was found for bovine D or OS, though the OS otherwise appeared similar to human OS. Geometric measurements of D and nonlysed OS showed a stable, maximal 2.1 +/- 0.1 fold increase in external plasma membrane surface area with osmotic swelling, identical for different-sized normal human platelets (mean volume V = 2.8-6.8 fl), for abnormally-large platelets (V = 8.7-11.6 fl), or for bovine or rabbit platelets (V = 3-4 fl). As osmotic swelling appears to primarily externalize SCCS in human platelets, the identical relative amounts of internal membrane externalized for bovine platelets is hypothesized to arise from an osmotically more labile, "closed", and structurally simpler SCCS or from a distinct membrane source than in human platelets. It appears that the surface to invaginated ("SCCS") plasma membrane is kept constant for human, bovine and rabbit platelets, independently of platelet production, size-dependent subpopulations, or of platelet ageing. PMID- 1523105 TI - Much ado about nothing. PMID- 1523106 TI - A path model of type A and type B responses to coping and stress in employed black women. AB - The purpose of this study was to test a conceptual model of the effects of age, weight, type, cholesterol, systolic blood pressure, and coping on the stress response of southern black women. Data were collected on 280 employed black women. Audiotape analyses of the structured interview resulted in 136 Type A's and 144 Type B's. Each individual was screened for hypercholesteremia using a portable reflectance photometer. Blood pressure measurements were taken every minute before, during, and after a stress-producing Type A/B interview. Type A's had higher resting systolic blood pressures, higher cholesterol levels, higher levels of stress during the interview, and lower coping scores than Type B's. The relationships between age, weight, and resting systolic blood pressures all were in the direction reported in the literature. PMID- 1523107 TI - Model for predicting work performance among persons with multiple sclerosis. AB - A causal model was tested on a sample of 201 MS subjects for the purpose of examining the role of selected demographic factors, work impediments, and work enhancers as predictors of activities essential for performing outside employment, home making, and for personal care. The results showed a relatively good fit of the model to the data through a number of indicators. Explained variance included: 9.0% in work impediments from the direct effect of age; 32.3% in work enhancers--A (job and environmental adjustment, social support, healthful practices) through direct effects from MS duration and work impediments; 9.8% in work enhancers--B (personal attributes) through direct effects from MS duration and work impediments; 61.1% in work performance through direct effects from the antecedent variables (age, education), stress-appraisal variable (work impediments), and coping variables (work enhancers-A, work enhancers-B). PMID- 1523108 TI - Increasing condom-use intentions among sexually active black adolescent women. AB - Whether a social cognitive theory AIDS prevention intervention would increase intentions to use condoms among 109 sexually active inner-city black female adolescents was tested. Analyses revealed that the women scored higher in intentions to use condoms, AIDS knowledge, outcome expectancies regarding condom use, and self-efficacy to use condoms after the intervention than before the intervention. Although increased self-efficacy and more favorable outcome expectancies regarding the effects of condoms on sexual enjoyment and sexual partner's support for condom use were significantly related to increased condom use intentions, increases in general AIDS knowledge and specific prevention related beliefs were not. PMID- 1523109 TI - Physiological and psychological variables related to functional status in chronic obstructive pulmonary disease. AB - The relationship of selected physiological and psychological variables to functional status in patients with chronic obstructive pulmonary disease (COPD) was investigated in this study. There has been limited exploration of the relative contribution of these variables to the performance of activities of daily living in this population. A convenience sample of 104 outpatients with COPD participated in the study. The independent variables were causal attributions, depressed mood, self-esteem, pulmonary function, and exercise capacity, and the dependent variable was functional status. There was a significant difference in functional status between those who did and those who did not ask the question, "Why me?" (p = .03). In addition, the remaining psychological variables and both physiological variables were significantly correlated with functional status (p less than or equal to .01). To identify the combination of study variables most predictive of functional status a multiple regression analysis was performed. The combined variables of exercise capacity and depression best predicted functional status (p less than .0001). It is concluded that both physiological and psychological factors are important in understanding functional status in this population. PMID- 1523110 TI - Standardization of a device to measure unsupported arm exercise endurance in chronic obstructive pulmonary disease. AB - The purpose of this study was to compare respiratory responses with moderate and slow rates of unsupported arm exercise (UAE) with a newly developed electromechanical device. Twenty-one patients with chronic obstructive pulmonary disease (COPD) were studied. Exercise endurance limits, metabolic, ventilatory and sensation outcomes were determined at rest prior to exercise and at end exercise endurance limits. Increases from baseline rest for both exercise rates were observed in: oxygen uptake, carbon dioxide production, inspiratory flow, minute ventilation, respiratory rate, dyspnea, respiratory effort, and arm fatigue. Endurance limits were similar for both rates of UAE. These data provide standards against which UAE in COPD can be evaluated. PMID- 1523111 TI - Temperature and temperature measurement after induced hypothermia. AB - This study was designed to assess factors associated with afterdrop, the fall in core temperature following completion of cardiac surgery, and determine the validity of noninvasive measures of temperature to predict core temperature in the severely hypothermic patient. Twenty-five postcardiac surgery patients served as subjects. Core temperature was measured using the pulmonary artery, bladder, and esophageal sites. The less invasive measures included a tympanic membrane thermometer, oral and axillary electronic thermometers, and a forehead surface temperature indicator. Temperatures were recorded every 10 minutes for 2 hours. End-of-surgery temperatures ranged from 30.3-38.3 degrees C (86.5-100.9 degrees F) with a mean of 36.02 degrees C (96.84 degrees F). Temperature change over the next hour ranged from a rise of 2.5 degrees C (4.5 degrees F) to a fall of 4.1 degrees C (7.2 degrees F). Factors associated with afterdrop included age, end-of surgery temperature (both positively) and body mass (negatively). No noninvasive measure appeared to be a valid indicator of core temperature in these hypothermic patients. PMID- 1523112 TI - Psychiatric rehospitalization of the severely mentally ill: patient and staff perspectives. AB - Research findings about psychiatric rehospitalization of severely mentally ill persons have provided few insights into its meaning for patients and staff. An attributional analysis of the causes schizophrenic patients and their staff gave for rehospitalization was used to test the limits of attributions theory in predicting how the event would be viewed. Results indicated that patients tended to give internal attributions for their readmission and believed that the cause was not under their control. Staff also attributed the problem to something internal to the patient, however, they were likely to see the cause as patient effort, which is under patient control. PMID- 1523113 TI - Effects of age on lump detection accuracy. PMID- 1523114 TI - Storage of research data: why, how, where? PMID- 1523115 TI - A measure of distress reaction to diarrhea in ventilated tube-fed patients. PMID- 1523116 TI - The consumer approach to recruitment of elder subjects. PMID- 1523118 TI - A secret procedure? PMID- 1523117 TI - The demotion of Helen LaMalle. PMID- 1523119 TI - The tip of the iceberg? PMID- 1523120 TI - A man of determination. Interview by Pete Bell. PMID- 1523121 TI - Danger rays. PMID- 1523122 TI - Unwanted advances. PMID- 1523124 TI - The other MarilynInterview by Niall Dickson. PMID- 1523123 TI - Splintering research. PMID- 1523125 TI - Confusions and challenges. PMID- 1523126 TI - Breaking down the barriers! PMID- 1523127 TI - Painful facts. PMID- 1523128 TI - Time for tea? PMID- 1523129 TI - Growing old in Greece. PMID- 1523130 TI - Attested development. PMID- 1523131 TI - Factors influencing psychiatric nurses' use of section 5(4). AB - A review of the literature suggests that little is known about the factors influencing the use of nurses' holding power under Section 5(4) of the 1983 Mental Health Act. This study aimed to redress this gap. Data were collected over one year by analysing the statistical returns of all wards within one mental health unit that used Section 5(4). It was found that it was used in the management of 3.8% of admissions. All but 4% of those detained were converted to an extended section. A number of variables were explored, the results of which suggest that psychiatric nurses' decision to invoke this section of the Act is not simply a case of patients being a danger to themselves or others but rather reflects an interplay of a number of factors. An awareness of such factors may reduce the necessity to implement this emergency nursing intervention. PMID- 1523132 TI - The challenge of change. PMID- 1523133 TI - Midwives' Journal. The booking-in interview. PMID- 1523134 TI - Midwives' Journal. Working mothers. PMID- 1523135 TI - Midwives' Journal. Interpreting statistics. PMID- 1523137 TI - [Effects of alpha and beta receptor blockaders on urinary excretion of sodium and potassium in healthy rats and in those with chronic renal failure]. AB - The aim the study was to investigate the effects of both alpha and beta adrenergic blockade on sodium and potassium excretion in rats with chronic renal failure. The chronic renal failure was induced by surgical ablation of 75% renal mass. Controls were shame operated rats. All experiments were performed under sodium pentobarbitone anesthesia. Blood pressure was measured intraarterially and glomerular filtration rate was estimated as inulin clearance. Phentolamine (4 micrograms/kg/min)--Group I; or propranolol (4 micrograms/kg/min)--Group II were infused i.v. to controls and chronic failure rats. alpha-receptor blockade with phentolamine lowered GFR and blood pressure to the same extent in controls and rats with chronic renal failure. alpha-blockade caused increased fractional sodium excretion only in controls while urinary excretion of sodium and potassium fell in rats with chronic renal failure. The beta-blockade with propranolol (4 micrograms/kg/min)--Group II did not affect both blood pressure and GFR either in controls nor in rats with chronic renal failure. However propranolol infusion increased sodium and potassium excretion in controls but not in rats with chronic renal failure. Our study showed the divergence in the role of adrenergic receptors in regulation of urinary electrolytes excretion between controls and rats with chronic renal failure. PMID- 1523136 TI - [Markers of HBV infection in drug addicts]. AB - Prevalence of markers of HBV infection was tested in two cohorts of drug addicts: in 140 addicts whose sera were drawn in the years 1985-1986 and in 100 addicts whose sera were drawn in the years 1988-1989. HBsAg was found in 10 (7%) patients in the earlier cohort and in 12 (12%) addicts in the latter, while at least one marker of HBV infection was present in 39% and 69%, respectively No correlation was found between the presence of markers of HBV infection and age, gender, or HIV status, however, duration of drug abuse increased the risk of HBV infection. There was no difference in mean titres of anti-CMV and anti-HSV-1 between subjects with and without HBV markers what suggests that the tested markers were specific. PMID- 1523138 TI - [Humoral immunologic response in myocardial infarction]. PMID- 1523139 TI - [Effects of alternating as well as long-term intensive polychemotherapy in the remission-maintaining treatment of patients with acute myelocytic leukemia]. AB - The paper presents the results of 2 year maintenance treatment of patients with acute myeloid leukemias using cyclic, rotating and intensive polychemotherapy. Complete remission (CR) was achieved in 22 out of 33 patients with doxorubicin (60 mg/m2; 1-3 days) and cytosine arabinoside (100 mg/m2; 1-7 days). All patients in CR entered into the authors' programme of intensification therapy consisting of two consecutive polychemotherapy cycles, using various combinations of amsacrine, doxorubicin, cytosine arabinoside, etoposide and 6-thioguanine repeated every 3-4 months. The mean survival so far is 18 months (range, 1-52 months). The projected 3-years survival rate in complete remission concerns 33% of the patients treated. Relapses occurred in 50% of the patients, within 10 months (range 1-35 mos.) after CR. Our results indicate that intensive cyclic polychemotherapy markedly prolongs the survival of AML patients. The high frequency of relapses during the first year after CR indicates the necessity to enhance the degree of aggressiveness of treatment shortly after a complete remission has been obtained. PMID- 1523140 TI - [Recurrent benign intrahepatic cholestasis syndrome]. AB - Up to now about 100 cases of benign recurrent intrahepatic cholestasis have been reported. In this case we give a description of familial form of this disease, in which cholestasis was associated with inflammatory liver response. A brief review of this rare condition and differential diagnosis have been presented. PMID- 1523141 TI - [Effect of salbutamol on heart rate in patients with atrial fibrillation]. AB - The influence of salbutamol aerosol on heart rate in patients with chronic atrial fibrillation was examined. The study comprised 15 patients (9 women and 6 man) in age 47-79 (mean 60) treated because of chronic obstructive pulmonary disease (COPD) with concomitant atrial fibrillation. The influence of salbutamol on heart rate was investigated during six hours ecg Holter monitoring (3 hours before and 3 hours after using salbutamol). The analysis showed that salbutamol aerosol in two doses increased heart rate calculated as mean heart rate per hour from 3 hours intervals from 4061 congruent to 1022.5 to 4185 congruent to 976 (p greater than 0.05). Mean value of blood pressure in one hour intervals did not change significantly. In patients with concomitant chronic atrial fibrillation and COPD salbutamol increased heart rate but difference between mean values before and after administration was not significant. PMID- 1523142 TI - [Clinical value of indirect automatic blood pressure determination in patients with atrial fibrillation]. AB - The value of indirect blood pressure in patients with atrial fibrillation was studied. Three methods were compared; single measurement, mean of three measurements and mean value of automatic measurement during 2-hours and whole day. The study comprised 13 patients; 7 men and 6 women aged 52-77 (mean 62.8 congruent to 6.6) hospitalized for cardiac diseases. The measurement were done using the mercury sphygmomanometer and auscultatory Korotkoff technique and automatic blood pressure monitoring (Acutracker--Medilog Oxford). The investigations showed that systolic and diastolic blood pressure during 24-hours monitoring were lower than single or repeated three measurements. The highest correlation coefficient to 24-hours recording was found for the mean value of 2 hours recording. It seems that blood pressure measurement in patients with atrial fibrillation (3-times in few minutes intervals) should be verified by using prolonged automatic recording. PMID- 1523143 TI - [Comparison of the effects of sodium fluoride and calcidiol on the remodeling of the endosteal surface of the rib cortex in dogs after administration of prednisone]. AB - The effects were compared of sodium fluoride and calcidiol on the remodeling of the rib cortical-endosteal surface of dogs treated with prednisone for long time periods. The study used a histomorphometric and tetracycline labeling methods. It was found that administration of sodium fluoride with calcidiol and calcium carbonate limited in a higher degree than the treatment with calcidiol and calcium carbonate the development of the osteoporotic changes induced by glucocorticoids. This included reduced enhancement of the bone resorption surface, increased bone formation surface and osteoid thickness connected with acceleration of mineralization rate. The changes induced by sodium fluoride had a favorable effect on the ratio of the resorption to the formation process at the sites of bone remodeling. PMID- 1523144 TI - [Manometric evaluation of the effects of intravenous administration of glucagon, buscopan and papaverine on the contractile activity of the sphincter of Oddi]. AB - Endoscopic manometric technique was used to investigate the effects of spasmolytic drugs on the sphincter of Oddi (s.O.) motility. 41 patients were randomly divided into 4 groups. In every patient the characteristics of the s.O. was monitored before and during 5 min. period after i.v. administration of: 20 mg buscopan, 1 mg glucagon, 40 mg papaverine or 2 ml of 0.9% NaCl solution. After buscopan administration the amplitude and frequency of phasic contractions of the s.O. were decreased as well as a baseline pressure in the s.O. Glucagon reduced frequency and amplitude of phasic contractions of the s.O. without influencing the baseline pressure. Papaverine reduced only frequency of phasic contractions. Physiological saline caused no change in pressure characteristics of the s.O. PMID- 1523145 TI - [Effect of bezafibrate on serum lipid, lipoprotein and apoprotein levels in patients with hyperlipoproteinemia type II and IV]. AB - The effect of six months' treatment with bezafibrate (400-600 mg daily) on serum lipids, lipoproteins and apolipoproteins concentrations was investigated in 32 patients with primary hyperlipoproteinemia (HLP) type IIa, IIb and IV. In all types of HLP the reduction of serum cholesterol (CH), triglycerides (TG), very low density lipoprotein (VLDL) fraction and increase in high density lipoprotein (HDL) cholesterol, HDL3-CH and apolipoprotein AI concentrations was observed. In type IIa and IIb HLP low density lipoprotein (LDL) cholesterol and apolipoprotein B levels decreased while in type IV increased. The greatest fall of serum CH concentrations was observed in type IIb while of serum TG level--in type IV. In 15 (46.9%) patients the side effects were noted. They were: abdominal pain, skin rash, myalgia, moderate increase in CPK and aminotransferase activities. Most of there side effects disappeared spontaneously without treatment cessation. PMID- 1523146 TI - [Bactericidal activity of plasma and leukocytes in patients after kidney transplantation]. AB - In renal transplant patients the plasma and leukocytes bactericidal activity was estimated towards the vivid bacterial cells of the standard strain of Staphylococcus aureus Oxford 209P. Considering the kind of the immunosuppression used, the patients were divided into two subgroups. The first subgroup comprised the patients treated with cyclosporin A and prednisone (12 persons) and the second one--the patients treated with azathioprine and with prednisone (19 persons). The control group consisted of 20 healthy persons. In the renal transplant patients significantly more bacterial cells survived the incubation with plasma and peripheral blood leukocytes and the reduction of bactericidal activity of the leukocytes alone was also found. The reduction of bactericidal activity of the peripheral blood leukocytes observed in the patients of the group tested may have resulted from the inefficient microbicidal systems of those cells. The kind of the immunosuppressive treatment did not seem to affect the bactericidal activity of the leukocytes and plasma examined in the renal transplant patients peripheral blood. It may be supposed that the increased susceptibility of those patients to bacterial, viral and mycotic infections is due in part to the reduced bactericidal capability of the peripheral blood leukocytes. PMID- 1523147 TI - [Calcitriol in chronic renal failure]. PMID- 1523148 TI - [Clinical picture and molecular disorders in myelodysplastic (MDP) syndromes]. PMID- 1523149 TI - [Peripheral T-cell lymphoma and leukemia (description of 4 cases and review of the literature)]. PMID- 1523150 TI - [Successful nitrogranulogen treatment of severe nephrotic syndrome in glomerulonephritis--case report]. AB - A patient with mesangio-proliferative glomerulopathy with advanced nephrotic syndrome (proteinuria 20 g/day) received bolus doses of corticosteroids (5 x 1.0 g iv) but renal function continued to deteriorate. A 11-day course of nitrogranulogen (0.01 mg/kg/day) with prednisone (0.5 mg/kg) caused complete disappearance of proteinuria with improvement in renal function. This observation supports our earlier findings indicating that treatment with low dose nitrogranulogen may be efficacious in some forms of glomerulopathies. PMID- 1523151 TI - [Treatment of cholelithiasis by extracorporeal shock-wave lithotripsy]. PMID- 1523152 TI - [Blood lipids in patients after kidney transplantation]. AB - In 50 kidney transplant patients [KTP] [37 of them were treated by cyclosporine A and prednisone--CyA group while 13 of them by azathioprine + prednisone--Aza group] serum levels of total cholesterol, LDL-cholesterol, HDL--cholesterol and triglyceride et different time intervals during the first three years after transplantation. The control group comprised 20 healthy subjects. KTP were characterized by significantly elevated plasma levels of total cholesterol, LDL cholesterol and triglycerides. In KTP treated by CyA+prednisone even an increase of plasma total cholesterol and LDL-cholesterol and a transitory decline of HDL- cholesterol were found as compared with respective basal values. From results obtain in this study it follows, that kidney transplantation does not normalize the lipid profile in KTP, and that KTP treated by CyA are characterized by more marked lipid abnormalities than those on azathioprine therapy. Time after successful kidney transplantation does influence significantly the lipid index of KTP. PMID- 1523153 TI - [Drug consumption by the patients with ischemic heart disease (IHD) studied by the Pol-Monica Warsaw and the effect of selected factors on the treatment of IHD]. AB - As part of a multicentre WHO MONICA-Project the present drug consumption by Warsaw population was assessed (evaluated by DDD). In Warsaw population 2646 inhabitants aged 35-64 years were examined. Ischaemic heart disease was diagnosed in 30% screened persons. Only 39% of subjects were involved in taking cardiovascular drugs. In ischaemic heart disease the drugs used most frequently were pentaerythritol tetranitrate and dipyridamole. The influence of several psychosocial factors on the fact of undertaking of pharmacological therapy was analysed using multivariant logistic function method. Significant relationships were found for age, health self-care self-estimation of health status and fact of medical consultation. Persons with high values of MLF (fifth quintile) underwent drug treatment six time more often, then persons with low values of MLF (first quintile). PMID- 1523154 TI - [24-hour ECG monitoring by the Holter system in early diagnosis of coronary disease]. AB - The aim of this study was to investigate the value of continuous ECG monitoring in early diagnosis of coronary heart disease. 312 patients (59 women, 253 men, aged 20-60 years) with chest pain since 3-6 months were studied. All patients underwent clinical examination, serum lipid determination, exercise ECG test, ambulatory ECG monitoring and coronary angiography. 194 patients had normal or nonsignificant irregularities of coronary arteries, in 118 patients significant atherosclerotic stenoses were found. Sensitivity and specificity of ECG monitoring were: 46 and 54% respectively. Significantly higher frequency of changes and longer duration of depression or elevation of ST segment in patients with significant coronary artery stenosis was found. ST segment changes without angina were observed in 23,7% of patients. PMID- 1523155 TI - [Exertion tolerance in the early period after myocardial infarction, the results of echocardiographic examination and the clinical course of infarction]. AB - The relation between exercise test, echocardiography and clinical course of acute myocardial infarction was investigated. 17-34 days after an acute myocardial infarction, before hospital discharge, 58 patients underwent exercise test and 17 28 days- echocardiography. Low exercise capacity was significant related to angina before infarction, maximal CKNAC and complications during clinical course. There was inverted correlation of asynergy index calculated from echocardiography with maximal workload achieved during exercise test. PMID- 1523156 TI - [Effect of metabolically uncompensated diabetes mellitus on mononuclear cell populations in peripheral blood]. AB - The study has been aimed at comparison of the number of peripheral blood mononuclear white cells in the E. SRBC, EA, EAC, SIg markers in patients with insulin dependent (type 1) and non-insulin dependent (type 2) diabetes and healthy donors. There was no marked difference in the numbers of surface markers E SRBC and SIg among the 3 groups. Significant increase in the number of cells with markers: FcIg and C3 fragment of complement was noted in patients with diabetes type 1 and type 2. No relation between the number of mononuclear cells in peripheral blood and the blood glucose level was observed. PMID- 1523157 TI - [Does hormonal activity of pheochromocytoma affect long-term prognosis in surgically treated patients?]. AB - 89 patients were operated upon for pheochromocytoma. 61 patients (37 women and 24 men) were available for follow-up. Mean age at operation was 39 +/- 12.3 yrs. Before operation paroxysmal and sustained hypertension were observed in 34 (55.7%) and 27 (44.3%) patients, respectively. Postoperatively permanent normalization of blood pressure was achieved in 38 cases (62.3%). All patients were divided into four groups. Group I with increased urine excretion of noradrenaline (NA) and adrenaline (A) consisted of 19 (31.1%) patients. Group II (increased NA excretion) included 27 (44.3%) patients. Group III comprised 3 (4.9%) cases with elevated A excretion. 12 (19.7%) patients with normal urinary excretion of catecholamines and increased excretion of methoxycatecholamines were alloted to group IV. Permanent normalization of blood pressure predominantly was observed in group IV--91.6%, whilst in group I, II and III this hypotensive effect was noted in 57.9%, 51.8% and 2/3, respectively. Permanent normalization of blood pressure can be mainly expected in patients with pheochromocytoma in whom catecholamines are rapidly inactivated within the tumor. PMID- 1523158 TI - A vasotocin-like peptide in Aplysia kurodai ganglia: HPLC and RIA evidence for its identity with Lys-conopressin G. AB - The presence of a vasopressin (VP)- or vasotocin (VT)-like peptide in the central nervous system of the gastropod mollusc Aplysia has been indicated previously. In the case of Aplysia californica, HPLC and RIA evidence suggested the peptide was VT-like but not identical with the nonmammalian vertebrate peptide [Arg8]VT (AVT). In the present study, anterior ganglia extracts from the related species Aplysia kurodai were analyzed by HPLC followed by RIA. Further analysis of the major AVT-IR peak showed it to be indistinguishable, in three distinct solvent systems, from the sea snail venom peptide Lys-conopressin G, but to be different from the vertebrate peptides [Arg8]VP (AVP), [Lys8]VP (LVP), AVT, oxytocin (OT), mesotocin, isotocin, aspargtocin, glumitocin, and valitocin, from the sea snail venom peptide Arg-conopressin S, and from the peptides [Lys8]VT and [Gln8]OT. In addition, the carboxymethylated (CM) A. kurodai peptide had the same HPLC retention time as CM-Lys-conopressin G. The HPLC/RIA results suggest that (i) based on the properties of the solvent systems used, the A. kurodai peptide has two basic amino acids (like the conopressins but unlike the vertebrate peptides), and (ii) there is a high probability that the A. kurodai peptide is identical with Lys-conopressin G. PMID- 1523159 TI - Isolation of FMRFa-like peptides from the DB-containing connective tissue of Helix aspersa. AB - The endocrine dorsal bodies (DB) of Helix aspersa are innervated by axons from the central nervous system, which establish synapse-like structures (SLS) with the DB cells. Previous immunocytochemical studies suggested the presence of FMRFa like substances in nerves of the DB area and in SLS. This paper reports on biochemical attempts undertaken in order to investigate the nature of these substances: the use of HPLC and RIA confirms the presence of three FMRFa-like peptides in the DB-containing connective tissue among which one is probably the FMRFa itself. PMID- 1523160 TI - Balance of glutamate and dopamine in the nucleus accumbens modulates self stimulation behavior after injection of cholecystokinin and neurotensin in the rat brain. AB - Subpopulations of dopamine (DA) neurons in the ventral mesencephalon have been reported to contain cholecystokinin (CCK) and neurotensin (NT), giving rise to DA, DA/NT, NT/CCK and DA/CCK/NT projections. More precisely, colocalized DA/CCK neurons project mainly to the caudal part of the medial nucleus accumbens, whereas its rostral portion receives CCK and DA nerve terminal networks that are structurally independent. We investigated the respective effects of both CCK and NT on the intracranial self-stimulation behavior (ICSS) from the posterolateral hypothalamus after their direct administration into the lateral ventricle (ICV), into both portions of the nucleus accumbens, into the ventral tegmental area (VTA), and into the subiculum of the hippocampal formation (SUB). The ICV injection of 150 pmol CCK8 induced a decrease in the rate of ICSS. By contrast, the direct administration of 150 pmol CCK8 into the mediocaudal part of the nucleus accumbens induced an enhanced rate of ICSS while a similar injection into its rostral portion gave rise to a slight transient decrease of ICSS. When injected into the SUB, both CCK8 and glutamate produced decreased rates of ICSS at femtomolar doses one thousand-fold under the picomolar concentrations used for ICV injections. Neurotensin induced similar behavioral profiles to that observed after the ICV injection of CCK8 or into both portions of the nucleus accumbens. Neurotensin and CCK8 displayed opposite effects on ICSS when administered into the SUB or into the VTA, suggesting they may regulate ICSS most probably through different synaptic mechanisms and through different anatomical pathways. PMID- 1523161 TI - Effect of a single dose of des-glycinamide-[Arg8]vasopressin or oxytocin on cognitive processes in young healthy subjects. AB - A single dose of des-glycinamide-[Arg8]vasopressin (DGAVP, 2 mg intranasal) or oxytocin (OXT, 20 IU intranasal) was given to female and male volunteers, respectively, in a placebo-controlled double-blind trial. Memory, vigilance, attention, and mood were tested starting 10 minutes after treatment. The DGAVP dose improved delayed recognition of abstract words when measured 1 week after treatment and reduced the intercept of a memory comparison task (Sternberg paradigm). A trend was present for DGAVP and OXT to affect learning, i.e., storage processes of verbal memory in an opposite way; DGAVP improved, while OXT attenuated initial storage and the rate of storage. No treatment effects on visual memory and vigilance were found. Of the mood measures, vigor was reduced immediately after treatment with OXT. PMID- 1523162 TI - Linear and cyclic beta-casomorphin analogues with high analgesic activity. AB - We investigated the antinociceptive efficacy of casomorphin (CM) derivatives using the vocalization test. Male Wistar rats received chronic microcannulae into the right lateral ventricle. One week later we examined the analgesic effect of CM derivatives 10, 30, 60, and 90 min after intraventricular injection (5 microliters). The analgesic effect was calculated as the individual percent increase in the pain threshold and was compared to controls (saline treatment). The substitution of D-lysine and D-ornithine in position 2 in connection with a cyclization through ring closure of the 2 position side chain amino group to the C-terminal glycine-COOH group resulted in high analgesic potency. The substitution of D-Pro4 was without any effect in the ineffective linear derivatives and decreased the effectiveness in the highly effective cyclic derivatives. The cyclic [D-Orn2]CM-5 and the cyclic [D-Lys2]CM-5 are the CM derivatives with the highest antinociceptive activity. The cyclic [D-Orn2]CM-5 is greater than 1000 times more effective than morphine. We conclude, on the basis of studies of receptor binding and in vitro investigations, that mu receptor activity alone is not responsible for the analgesic activity. The delta receptor and possibly also the kappa receptor could modulate the nociceptive effectiveness. PMID- 1523163 TI - Structural characterization of neuropeptide Y from the brain of the dogfish, Scyliorhinus canicula. AB - A peptide of the pancreatic polypeptide (PP) family was isolated in pure form from the brain of an elasmobranch fish, Scyliorhinus canicula (European common dogfish). The primary structure of the peptide was established as: Tyr-Pro-Ser Lys-Pro-Asp-Asn-Pro-Gly-Glu10-Gly-Ala-Pro-Ala-Glu-Asp- Leu-Ala-Lys- Tyr20-Tyr-Ser Ala-Leu-Arg-His-Tyr-Ile-Asn-Leu30-Ile-Thr-Arg- Gln-Arg-Tyr-NH2. This sequence contains only two amino acid substitutions compared with pig neuropeptide Y (NPY) (Gly for Asp11 and Lys for Arg19), and two substitutions (Gly for Asp11 and Leu for Met17) compared with frog NPY. The amino acid sequence of NPY from dogfish brain is appreciably different from the neuropeptide Y-related peptide previously isolated from dogfish pancreas (five amino acid substitutions). The data indicate that evolutionary pressure to conserve the complete primary structure of neuropeptide Y has been very strong. It is suggested that the NPY-related peptide present in the pancreas of elasmobranch and teleost fish represents the piscine equivalent of mammalian peptide tyrosine tyrosine (PYY). PMID- 1523164 TI - Biological effects of human gastrin I and II chemically modified at the C terminal tetrapeptide amide. AB - Binding to gastrin receptors and gastric acid secretion experiments were performed with gastrin derivatives modified at the C-terminal tetrapeptide amide from HG-13 sequence. 1. When the ultimate phenylalanine amide was replaced by a phenethylester or a phenetylamide moiety, the resulting compound bound to gastrin receptors (Kd approximately 10 nM) and exhibited antagonist activity on gastrin induced acid secretion in the anesthetized rat. 2. Changing the peptide bond between Trp and Leu residues to a -omega(CH2-NH)- bond resulted in a compound which also bound to gastrin receptors (Kd approximately 10 nM) but presented agonist activity on acid secretion in the rat. In contrast, when the peptide bond between Leu and Asp residues was replaced by a -omega(CH2-NH)- bond, the resulting compound was devoid of any affinity for gastrin receptor (Kd greater than 10(-6) M) and of any biological activity. 3. The HG-13 derivatives were synthesized in sulfated and unsulfated forms: O-sulfation of the HG-13 tyrosine residue did not change its intrinsic in vivo activity but enhanced its affinity for gastrin receptors (Kd approximately 0.3 nM). On the contrary, O-sulfation of the various chemically modified HG-13 had no significant effect in either in vitro or in vivo experiments. 4. Finally, no significant difference between binding on parietal (F3) and nonparietal (F1) cells was observed, in agreement with the presence of a gastrin-type receptor in these two cell populations. PMID- 1523165 TI - Hypothalamic neuropeptide Y disturbances in the obese (cp/cp) JCR:LA corpulent rat. AB - Regional hypothalamic neuropeptide Y (NPY) concentrations were compared between cp/cp JCR:LA corpulent rats, which were grossly obese, hyperphagic, and hyperinsulinemic, and lean (+/+) controls. In freely fed cp/cp rats, NPY levels in the arcuate nucleus (ARC) were 31% higher than in lean rats (p less than 0.001). In lean rats, chronic food restriction significantly raised NPY levels by 22% in the ARC (p less than 0.05) and by 44% in the dorsomedial nucleus (DMH; p less than 0.05). By contrast, food-restricted cp/cp rats showed no change in the ARC, but NPY levels rose in the DMH (by 36%; p less than 0.05) and ventromedial nucleus (31%; p less than 0.05). Increased NPY levels in the ARC, the major site of hypothalamic NPY synthesis, suggests increased NPYergic activity in cp/cp rats; given the central actions of NPY, this could contribute to hyperphagia, obesity, and hyperinsulinemia in this syndrome. Abnormal NPY responses to food deprivation further suggest dysregulation of NPY in cp/cp rats. PMID- 1523166 TI - Regulation of cholecystokinin secretion from a rat medullary thyroid carcinoma cell line: role of calcium, cyclic nucleotides, glucocorticoids, neurotensin, and calcitonin gene-related peptide. AB - CCK-secreting WE rat medullary thyroid carcinoma cell line resembles other calcitonin-producing (C-cell) lines in that calcium, cAMP, or agents which raise cAMP, dexamethasone, and beta-adrenergic agents all stimulate peptide secretion. Unlike other C-cell lines, the WE cells respond similarly to IBMX (3-isobutyl-1 methyl-xanthine, a phosphodiesterase inhibitor) in the presence and absence of forskolin, implying that these cells secrete substances that raise cAMP levels, whose effect is accentuated by IBMX. Both CGRP and neurotensin, peptides that may be secreted by these cells, caused a small, but significant, increase in CCK secretion. It is possible that these or other secreted substances that activate adenylate cyclase are responsible for the cell's high rate of CCK secretion. Their high rate of CCK synthesis and their regulated secretion suggest that these cells will be a good model for studies of CCK expression, biosynthesis, and processing. PMID- 1523167 TI - Uptake and metabolism of [3H]-Leu-enkephalin following either its intraperitoneal or subcutaneous administration to mice. AB - The uptake and metabolism of 30 micrograms/kg [3H]-Leu-enkephalin ([3H]-LE) following either intraperitoneal (IP) or subcutaneous (SC) administration to Swiss Webster mice was examined. Uptake of [3H] was rapid, with peak levels of radioactivity in plasma observed at 5 or 10 min following IP or SC peptide injection, respectively. The majority (80-99% +/- 0.8) of plasma radioactivity at all postinjection plasma collection time points was in the form of tyrosine containing enkephalin metabolites, indicating a substantial and rapid in vivo hydrolysis rate for exogenously administered LE. Leu-enkephalin is metabolized in vivo faster than previously reported in vitro in mouse plasma. However, despite this extensive hydrolysis, levels of intact LE remaining in plasma following its systemic administration are within or above endogenous LE plasma levels. PMID- 1523168 TI - Synthesis and in vitro evaluation of [Leu13]porcine motilin fragments. AB - Several peptide fragments representing N-terminal, C-terminal, and internal sequences of [Leu13]porcine motilin ([Leu13]pMOT) were synthesized using Fmoc solid phase methodology. Peptides were assayed for motilin receptor binding activity in a rabbit antrum smooth muscle preparation and for stimulation of contractile activity in segments of rabbit duodenum. In vitro activity was directly correlated with motilin receptor binding affinity for all [Leu13]pMOT fragments examined. N-Terminal fragments of just over half the length of the native peptide are nearly equipotent as full-length motilin. These results suggest that the N-terminal segment, together with residues from the mid-portion of the molecule, constitutes the bioactive portion of pMOT. The C-terminal segment, in contrast, contributes little to receptor binding affinity or in vitro activity. PMID- 1523169 TI - Hemodynamic effects of calcitonin in the normal rat. AB - Calcitonin (CT) was administered acutely (IV 4-8 U/kg) and chronically (SC 2 U/kg/day x 150 day) to normal male rats. Measurements included heart rate (HR), mean blood pressure (MBP), cardiac index (CI), peripheral vascular resistance (PVR), and stroke volume index (SVI). The MBP was higher in CT rats examined under pentobarbital anesthesia. Upon awakening from anesthesia, rats chronically on CT exhibited impaired recovery of CI and SVI. Hemodynamic effects were not seen in rats acutely treated with CT. Heart weight was unchanged in chronic treatment with CT. Therefore, CT had minimal hemodynamic effects in the normal male rat. PMID- 1523170 TI - Differential effects of amylin on memory processing using peripheral and central routes of administration. AB - Amylin is a peptide hormone secreted from the beta cells of the pancreatic islets. Amylin was administered peripherally or centrally following weak or strong training on footshock avoidance conditioning in a T-maze. Under conditions of weak training, amylin improved memory retention in a dose-dependent manner. Under conditions of strong training, it impaired retention over the same dose range. Central administration of amylin in mice given strong training impaired retention but had no effect on the retention of mice given weak training. These findings suggest that the mechanisms of action by which amylin altered memory processing are different for peripheral and central administration. Peripherally secreted amylin may play a role in the amnesia seen in diabetes and the memory enhancement following glucose administration. PMID- 1523171 TI - Identification of four chicken gastrins, obtained by processing at post-Phe bonds. AB - Chicken antrum was found to contain 7 nmol/g of carboxyamidated gastrin/CCK-like peptides. The predominant chicken gastrin (so named due to the antral origin) contained 53 amino acid residues: DWPEPPSQEQ QQRFISRFLP HVFAELSDRK GFVQGNGAVE ALHDHFYPDW MDF-NH2. Three smaller (less abundant) forms corresponded to the 30-, 21-, and 7-residue carboxyamidated C-terminal fragments. The major part was sulfated at the tyrosine residue in position seven from the C-terminus. A lower isoelectric point and abrupt termination of the sequencing suggest that some of the peptides had an isoAsp-Gly bond instead of an Asn-Gly bond. The three shorter forms were all derived from the precursor by post-Phe cleavages. This cleavage pattern suggests a processing enzyme specific for bonds between Phe and moderately hydrophobic residues. PMID- 1523172 TI - Sex differences in the effects of neuropeptide FF and IgG from neuropeptide FF on morphine- and stress-induced analgesia. AB - There is evidence suggesting that the endogenous mammalian octapeptide FLFQPQRFamide (F8Fa or neuropeptide FF, NPFF) has modulatory effects on opioid mediated analgesia in rodents. There is also substantial evidence for sex differences in opioid analgesia, whereby male rats and mice display greater levels of opioid-mediated analgesia than females. In the present study, determinations were made of the effects of NPFF and IgG from antiserum against NPFF on morphine- and restraint stress-induced opioid analgesia in male and female deer mice. Intracerebroventricular (ICV) administrations of NPFF (0.10-10 micrograms) reduced in a dose-dependent manner morphine- and stress-induced analgesia in both male and female mice, with NPFF having markedly greater antagonistic effects in the male than female mice. Additionally, ICV administrations of NPFF-IgG increased the levels of morphine- and stress-induced analgesia and significantly reduced basal nociceptive sensitivity in male mice, whereas, in female mice, NPFF-IgG had no significant effects on either opioid mediated analgesia or nociceptive sensitivity. These results indicate that there are sex differences in the modulatory effects of NPFF on opioid-mediated analgesia. PMID- 1523173 TI - Effects of corticotropin releasing hormone on appetitive behaviors. AB - Corticotropin releasing hormone (CRH) is a 41-residue hypothalamic neuropeptide that has been shown to have potent behavioral effects in animals and has been implicated in clinical disorders in man. This review focuses on those aspects of the behavioral effects of CRH related to food-associated behaviors. The effects of CRH on food intake are compared with its effects on performances maintained by food presentation, and contrasted with the effects of CRH on performances maintained by other events. The effects of CRH antagonists and drugs that interact with the behavioral effects of CRH are also reviewed, particularly with respect to their direct effects on food intake. Lastly, data assessing the effects of CRH administration on central neurotransmitter levels are presented and compared with levels seen in clinical populations. The effect of CRH on food intake seen in animals is consistent with a putative role for CRH in clinical syndromes where appetite suppression is apparent. Since some of the effects of CRH on food intake are subject to pharmacological intervention, strategies directed at peptidergic mechanisms of psychiatric disorders should be explored. PMID- 1523174 TI - Effects of high temperature on growth and efficiency of male and female broilers from lines selected for high weight gain, favorable feed conversion, and high or low fat content. AB - Male and female broiler chicks from five different broiler crosses (WI, LF, and HF = Israeli chicks selected for high body weight gain, and low and high abdominal fat, respectively; FC and WN = Dutch chicks selected for favorable feed conversion and high body weight gain, respectively) were raised at a high ambient temperature (32 to 33 C). Weight gain, protein and fat content in the carcass and feed, and protein efficiency were determined at 4, 6, and 8 wk of age. The effect of the high temperature was evaluated by comparing these data with those of similar chicks raised at a normal temperature (20 to 33 C) up to 6 wk of age. The reductions in body weight, protein gain, and feed and protein efficiency due to the high temperature increased with age and were much larger in males than in females. This trend was more pronounced in WI and WN chicks than in LF, HF, and FC chicks. Females of WI and WN crosses were as heavy as males at 6 wk and heavier at 8 wk. In LF, HF, and FC crosses, both sexes had similar weights at 8 wk. Growth reduction due to the high temperature was largest in the groups with the highest growth rate at the normal temperature (WI and WN males). Chicks with a lower growth rate and a higher capacity for energy storage in fat depots (all females, HF chicks), or a higher capacity for heat loss (FC chicks), were less affected by the high temperature. The results suggest that females should be preferred over males for broiler production in hot facilities or locations. Broiler genotypes selected for feed efficiency at the expense of fast growth may allow for a more profitable broiler production in high-temperature regions. PMID- 1523175 TI - Deoxyribonucleic acid fingerprint bands linked to loci coding for quantitative traits in chickens. AB - Efficacy of DNA fingerprint (DFP) bands in marker-assisted selection programs for quantitative traits in chickens was evaluated. A cross between two populations of White Plymouth Rock chickens that had been selected for 31 generations for high (HW) or low (LW) 8-wk body weight served as the base population for the experiment. Full- and half-sib families were produced over four generations and 400 offspring were measured for body weight at 8 wk (BW8) and shank length at 12 wk of age (SL12). Distributions were constructed for each quantitative trait in offspring of one F1 sire. The DFP produced from mixed blood of the individuals within each tail of the distribution were compared. From a total of 13 DFP bands that were disparate in intensity between the tails, four bands were chosen for analysis. Matings were made between males and females based on the presence or absence of these bands, but were limited to individuals that were within .5 standard deviation of the mean for the distribution of a particular trait. Quantitative traits of the resulting progeny were analyzed to determine whether parental type (presence or absence of the DFP band) influenced expression of the trait in the offspring. One band out of the four tested was associated with SL12, was an effective predictor of phenotype for both SL12 and BW8, and appeared to be inherited in a dominant fashion. PMID- 1523176 TI - A feather-sexed strain of laying hens was more responsive to dietary supplements of choline and methionine than a vent-sexed strain. AB - A response surface design was used to study Cho and Met interactions with corn and soybean diets, using two strains of hens. The strains were a feather-sexed line (FS strain), and a vent-sexed line (SS strain). The diets contained 3% meat and bone meal and, on chemical analysis, 15.1% crude protein, .29% Met, .225% Cys, and 1,041 ppm of Cho. Nine diets were fed from 20 to 68 wk of age, using added Met levels ranging from 0 to 500 ppm and added Cho levels ranging from 0 to 1,500 ppm, to fix the design points. The FS strain consumed significantly more feed per day (117 versus 108 g) than the SS strain, but there were no significant differences for the 24 to 68 wk period in egg production, egg weight, or feed per dozen eggs. Three and five combinations of Met and Cho were significant in improving egg production (P less than .05) out of the eight combinations for the SS and FS strains, respectively. The best egg production for the FS strain for the period 24 to 68 wk was observed at 250 ppm Met and 1,500 ppm Cho, or 427 ppm Met and 220 ppm added Cho. The SS strain showed no significant (P greater than .05) dietary responses in egg production between 250 ppm Met and no Cho, or 427 ppm Met and either 220 or 1,280 ppm Cho. The SS strain showed no significant (P greater than .05) dietary response in egg weight to either Cho or Met.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1523177 TI - The effect of light source and intensity on turkey egg production. AB - The effect of light source and intensity on egg production, fertility, hatchability, egg weight, and shell quality in turkey hens was investigated. Turkey hens were exposed to either incandescent, high-pressure sodium vapor (HPSV), or daylight fluorescent (FL) lights at an intensity of 21.6 1x during the growth phase (after 8 wk). During the breeder phase, hens were assigned to the same light sources at light intensities of either 53.8 or 166.4 1x in a 3 x 3 x 2 factorial arrangement of treatments. Light source during the growth phase had no significant effect on subsequent egg production, egg weight, fertility, or hatchability. Egg production, shell quality, fertility, and hatchability were also unaffected by light source or intensity during the breeder phase. Egg weight was significantly increased in hens exposed to HPSV compared with incandescent lights during the breeder phase. The HPSV and FL lights can be used effectively for turkey breeder hens both during the prebreeder and breeder periods. Furthermore, light intensities of 53.8 and 166.4 1x appear to be equally effective in stimulating production. PMID- 1523178 TI - Effect of number of hens per nipple waterer on the performance of several strains of layers in cages. AB - Two experiments were designed to study the effects of housing in cages with several hens per nipple waterer (HPN) ratios on performance of several strains of White Leghorn pullets. In Experiment 1, only body weight gain and water consumption were significantly affected by the HPN; hens at the 2:1 HPN gained more weight and consumed more water per day than those at the 4:1 HPN. The lack of a significant strain by HPN interaction indicated that the four strains responded similarly to the different HPN ratios. In Experiment 2, hens in cages with 3.5:1 and 7:1 HPN consumed significantly more water and feed than those in cages with 10:1 and 14:1 HPN. In both experiments, the HPN had no significant effect on age at sexual maturity, egg production, mortality, and egg weight, but efficiency of feed usage for egg production decreased with the 3.5:1 and 7:1 HPN. PMID- 1523179 TI - Effect of early feed restriction on growth, feed conversion, and mortality in broiler chickens. AB - Two floor pen and two battery experiments were conducted to determine the effects of early feed restriction on the performance of commercial broilers. Feed restriction was induced in all experiments by providing chicks with 40 kcal of ME per bird per day, commencing at 4 days of age. Male chicks were feed-restricted for 7 (Experiments 1 and 2) or 6 days (Experiments 3 and 4), whereas broiler females were restricted for 5 days (Experiment 1). Ad libitum feeding was resumed after the restriction periods, and continued through the conclusion of the experiments at 49 (Experiments 1 and 2) or 28 (Experiments 3 and 4) days of age. Broilers provided ad libitum access to feed for the entire experimental period served as the controls in each study. Broilers subjected to an early feed restriction had significantly (p less than or equal to .05) lower mean body weights than controls for all ages measured in the four experiments. However, feed conversion ratios for restricted broilers were significantly lower at 28 (Experiments 1 through 4) and 49 (Experiments 1 and 2) days of age than for birds consuming feed ad libitum. Through regression analyses, it was estimated that male broilers in Experiments 1 and 2 would require approximately 2 additional days to obtain body weights similar to those observed in control broilers and would still maintain a lower feed conversion ratio at this older age. In Experiments 1 and 2, weekly body weight gains for restricted broilers were significantly lower than for controls from 0 through 28 days of age. However, restricted broilers (7 days) in Experiment 2 had significantly higher rates of gain from 29 to 49 days of age than unrestricted controls. Total pen body weights for restricted and ad libitum groups were similar at 49 days of age in Experiments 1 and 2, which reflected the significant difference in mortality observed between the two groups. PMID- 1523180 TI - Issues facing researchers. AB - Agriculture research spans the spectrum from fundamental to applied research. Researchers in agricultural fields must compete successfully with scientists in their field of research for funding during a time of diminishing resources. In addition, there are pressures on agricultural researchers within their institutions and at the state and national levels that often differ from pressures on scientists in fields other than agriculture. In order to be successful, the poultry scientist must compete for funds, keep current in a rapidly advancing technological environment, and attempt to meet the needs of the poultry industry. PMID- 1523181 TI - Legislative view of research. AB - Congress has its own perception of research; whether it equates to reality is up to the research community. Many in Congress perceive that the research community is free-floating and is not focused on addressing the problems that face the United States today. Recent government reports have reviewed the purposes, accountability, and challenges facing the traditional research and extension system as it enters the 1990s. These reports send a strong message that the status quo will not work sufficiently in the 1990s. How does this affect agricultural research dollars? Congress, in response to its own perceptions, has strived to establish priorities by allocating resources to key projects. Whether this is in the best interest of the nation is debatable. The agricultural research community needs to establish priorities and to communicate them effectively; otherwise someone less informed in the Congress will do it. PMID- 1523182 TI - Oocysts of Eimeria in the litter of broilers reared to eight weeks of age before and after withdrawal of lasalocid or salinomycin. AB - Forty-six broiler houses were examined for the presence of oocysts of Eimeria in the litter before and after withdrawal of lasalocid or salinomycin from the feed. A decrease in number of small oocysts (Eimeria acervulina or Eimeria mitis) was observed following withdrawal of medication. Numbers of medium-sized oocysts (probably Eimeria tenella) remained the same, but an increase in large oocysts (Eimeria maxima) was recorded. No lesions attributable to Eimeria tenella were found in the ceca of birds after withdrawal of the drug. More small- and medium sized oocysts were found at sites with new litter than at sites where the litter had been employed for previous flocks. No difference in the number of oocysts was found, whether birds were reared on oak shavings or a mixture of pine shavings and rice hulls. The number of oocysts was positively correlated with the moisture content of the litter, but there was no correlation between oocysts present and the final BW or feed conversion of the birds. Moisture levels were highest (after withdrawal of drug) for new litter or oak shavings. There was no correlation between moisture content of the litter and BW or feed conversion. PMID- 1523183 TI - Effect of dietary calcium level on medullary bone calcium reserves and shell weight of Leghorn hens. AB - Two experiments were conducted to determine the effect of different levels of dietary Ca and subsequent feeding of a very low level of Ca on the medullary bone Ca reserves of laying hens. In Experiment 1, a total of 30 40-wk-old Single Comb White Leghorn hens were offered a diet with 2.5, 3.5, or 4.5% Ca for a period of 21 days with 10 birds per dietary treatment. On Day 21, five hens from each dietary treatment were euthanatized. The remaining birds were offered a .46% Ca diet for 5 days. In Experiment 2, 25 Single Comb White Leghorn hens were fed a 3.5% Ca diet for 21 days. Hens were then offered a .46% Ca diet and five hens euthanatized on Days 0, 2, 3, 5, and 7 of feeding the low-Ca diet. In Experiment 1, dietary Ca level had a significant (P less than .05) effect on total medullary Ca reserves of laying hens. Previous dietary Ca level had no significant (P greater than .05) effect upon medullary bone Ca reserves after subsequently feeding the low-Ca diet for 5 days. There was a (P less than .05) significant reduction in medullary bone Ca reserves of hens, regardless of previous level of calcium fed. In Experiment 2, feeding a low level of dietary Ca resulted in a significant (P less than .01) reduction in medullary bone Ca reserves of all bones measured, except the humerus. Although there was a significant (P less than .05) reduction in medullary bone Ca during the depletion period, hens appeared to make some attempt to conserve medullary bone Ca reserves. PMID- 1523184 TI - Dietary poultry fat and gastrointestinal transit time of feed and fat utilization in broiler chickens. AB - An experiment was conducted with broiler chicks to determine the effect of 0, 5, 10, and 20% supplemental poultry fat and age on gastrointestinal transit time (GTT) and the effect of supplemental fat on fat utilization and growth. Mean GTT, measured with chromic oxide or ferric oxide, was not affected by supplemental fat. There was a curvilinear relationship (rising ogive) between mean GTT and age. It increased from an estimated lower plateau of 170 min to an upper plateau of 211 min with the inflexion point at 3.23 wk. At 6 wk of age, birds receiving supplemental fat consumed more energy and were heavier and more efficient. Total lipid digestibility increased with supplemental poultry fat but digestibility of poultry fat was not altered. The AME of poultry fat ranged from 8.1 to 8.4 kcal/g at 5 to 20% inclusion in the diet. PMID- 1523185 TI - Effects of protein and amino acid level fed zero to forty-two days on response of broilers to protein and amino acid levels fed forty-two to forty-nine days of age. AB - Three studies were conducted to evaluate the effect of protein and amino acid (AA) levels fed 0 to 42 days posthatch on response of broiler chickens to levels of protein and AA fed during the finisher period. Birds were grown to 42 days on diets formulated to contain a minimum of 105 or 120% of recommended AA levels, and then randomly assigned to diets formulated to contain a minimum of 70, 80, 90, 100, 110, or 120% of recommended AA levels for 42 to 49 days. No minimum protein level was imposed on the diets. Body weight, feed intake, feed utilization, dressing percentage, abdominal fat content, and parts yield were determined. The protein and AA level fed 0 to 42 days had significant effects on 42- and 49-day body weight and 42- to 49-day feed intake of male but not female broilers. However, there was no interaction of protein and AA levels fed 0 to 42 days on response to protein and AA levels fed 42 to 49 days for these criteria. Weight gain, feed intake, and feed utilization of both males and females 42 to 49 days were significantly influenced by protein and AA levels fed during this time; protein and AA requirements of females during this time appeared to be equal to, or greater than, those of the male broiler. Although there were significant interactions of protein and AA levels 0 to 42 and 42 to 49 days on various carcass parameters for both male and female broilers, these followed no consistent pattern. Protein and amino acid levels fed 0 to 42 days had a significant influence on both quantity and percentage of abdominal fat in both male and female broilers processed at 49 days but not on any other carcass parameters. The protein and AA levels fed 42 to 49 days had a significant effect on both quantity and percentage of abdominal fat in male but not female broilers. The protein and AA levels fed 42 to 49 days significantly influenced quantity but not percentage of breast meat in male but not female broilers. The results of the current study indicate that there was minimal carryover effect of protein and AA levels fed 0 to 42 days on response to AA levels fed 42 to 49 days. PMID- 1523186 TI - Relationship of hen age and egg sequence position with fertility, hatchability, viability, and preincubation embryonic development in broiler breeders. AB - Indian River broiler breeder hens (n = 29) were caged individually to investigate whether hen age and egg sequence position were related significantly to the dependent variables fertility, hatchability, viability (hatch of fertile eggs), and preincubation embryonic development. Hens were artificially inseminated once per week. All eggs laid during the period of 31 to 54 wk of age were stored at 16 to 17 C for .5 to 7 days. Time of oviposition records were used to assign eggs to sequence position ("first" or "subsequent"). Eggs laid on odd-numbered weeks were broken open, fertility determined, and embryonic development staged. Eggs laid on even-numbered weeks were sent to a commercial hatchery to assess hatchability. Unhatched eggs were opened to determine fertility and embryonic mortality. In addition, hen weight, number of days since insemination, time of oviposition, and egg weight were recorded to determine their relationship to the dependent variables. Fertility (n = 3,240 eggs) and hatchability (n = 1,653 eggs) were not significantly related to egg sequence position, but were related to hen age (P = .0001 and P = .0002, respectively). Older hens demonstrated lower fertility and hatchability. In contrast, embryo viability (n = 1,487 eggs) and preincubation embryonic development (n = 1,200 eggs) were not significantly related to hen age, but were related to egg sequence position (P = .0026 and P = .0001, respectively). First-of-sequence eggs had lower viability, and embryos of these eggs were more developed than embryos of subsequent eggs. These data indicate that the reduction in chick production observed as the hen ages may be due to the increased incidence of first-of-sequence eggs. PMID- 1523187 TI - The effectiveness of ligating or detaching ceca as an alternative to cecectomy. AB - Cecectomy (the surgical removal of ceca) is a technique that has been used to explore the nutritional and osmoregulatory role of the ceca in domestic fowl and other birds. The operation imposes a high level of physiological stress on a bird. The current study describes the effectiveness of ligating or detaching the ceca in young turkeys as an alternative to complete removal of the organ. Birds with ligated ceca showed less postsurgical depression and initiated feeding and other normal activities sooner than birds with detached ceca. Birds with detached ceca also had a significantly slower rate of weight gain 1 wk after surgery. Both surgically treated groups were more depressed than were sham-operated turkeys. Post-mortem examinations revealed that cecal detachment was more successful in actually separating the ceca from the rectum and in preventing flow of digesta in and out of the ceca. Evidence of growth of cecal stumps that remained attached to the rectum was found following both ligation and detachment. Post-mortem examinations revealed that in four birds both ligated or detached ceca left in the abdominal cavity became enlarged and filled with a dark, pasty, odorous substance. This increase in cecal size and volume of contents with time apparently indicates that some microbial metabolic activity continued in the cecal lumen. If so, this might have negative implications for studies that assume that such ceca are no longer functional. PMID- 1523188 TI - A rapid method for the determination of temperature abuse of fresh broiler chicken. AB - Ready-to-cook broiler chicken carcasses were obtained immediately postchill from a commercial processing plant. A control group was held at 4 C for 10 days. Test groups were held at 4 C for 2 days, temperature abused at 10, 15, or 20 C for 0, 1, 2, 4, 6, 8, 12, or 24 h, and then held at 4 C for an additional 4 days. Both control and test birds were sampled using whole carcass rinse techniques and bacteria enumerated using impedance detection times (DT) and total plate count (TPC) techniques at incubation temperatures of 18 and 42 C. The DT and TPC showed a significant increase (P less than .05) in the number of organisms recovered at 18 C but did not show a significant increase (P less than .05) in organisms recovered at 42 C when carcasses were held at 4 C continuously for up to 10 days. Carcasses that were temperature abused at 10 C for up to 24 h were not significantly different (P less than .05) from the unabused controls, using either DT or TPC, following incubation at 18 and 42 C. At an incubation temperature of 18 C, carcasses abused at 15 or 20 C had significantly more growth of bacteria than controls at 1, 6, 12, and 24 h and 4, 8, and 12 h as determined by DT and at 6, 12, and 24 h and 1, 2, 4, 8, and 12 h, respectively, as determined by TPC.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1523189 TI - Research note: open-field behavior of Japanese quail chicks genetically selected for low or high plasma corticosterone response to immobilization stress. AB - Open-field behavior was examined in Japanese quail chicks genetically selected for either reduced (LS, low stress) or exaggerated (HS, high stress) plasma corticosterone response to immobilization stress. Chicks of the LS line showed less freezing and ambulated sooner than did their HS counterparts. These findings suggest that exposure to an open-field or novel environment elicited less fear in LS than in HS chicks. They also support the suggestion that fearfulness and adrenocortical activation are positively associated and indicate that selection for differential adrenocortical responsiveness exerted concomitant effects on fear-related behavior. PMID- 1523190 TI - Research note: maintenance of duodenum weight during a molt induced by dietary zinc in a low-calcium diet. AB - The duodenal loop was excised from hens that had been induced to molt by a low calcium diet containing 2,800 ppm zinc in the form of zinc sulfate heptahydrate. This was compared to that of hens pair-fed a layer diet. In Experiment 1, hens exhibited an increased duodenum weight after receiving the zinc diet for 14 days but no differences remained 14 days later. In Experiment 2, increased duodenum weight was noted after 4 days on the zinc diet and this persisted through 10 days. This greater tissue weight was observed whether expressed on a wet or dry weight basis. Thus, there was a persistency of tissue mass. The duodenum does not regress during a zinc-induced molt as it does during a fast-induced molt. PMID- 1523191 TI - The influence of mercury on the secretion of human chorionic gonadotropin in superfused young placental tissue. AB - The effect of mercury (Hg), as HgCl2, in levels ranging from 0.75 to 12 micrograms/ml medium, on the secretion of human chorionic gonadotropin (hCG) was examined in first-trimester placental explants, after 6 or 24 hr incubation, employing both static and dynamic systems (the latter by superfusion). Later the unbound Hg was washed for 45 min. with fresh medium devoid of Hg, followed by superfusion with the latter medium for 75 min., during which time samples were collected for hCG assay. For the superfusion experiments the parameters used for evaluating the hCG secretion pattern were: mean peak amplitude, pulse frequency and the area under the hCG secretion curve (AUC). The results observed after 24 hr incubation indicate that in the dynamic system the hCG secretion increased significantly, and this increase was dose-dependent. There was also a dose related increase in mean total hCG secreted by the explants exposed to Hg. Maximal hCG secretion was observed after 24 hr exposure of explants to 6 micrograms of the metal/ml. Both the mean peak amplitude and AUC parameters showed a statistically-significant increase for this dose level. At 12 micrograms/ml, the pulsatile secretion of hCG decreased, but the value for the mean hCG secretion was still higher than that observed for 0.75 and 3 micrograms/ml. After 6 hr incubation, however, there were no significant changes from the control, as judged by all of the above parameters. The levels of hCG secreted by the explants into the media in the static system were not significantly different from their respective controls, for both incubation periods and Hg levels.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1523193 TI - Saturation analysis in receptor binding assays: an evaluation of six different calculation techniques. AB - Randomized errors to varying extents have been introduced in a constructed data set stimulating receptor binding saturation analyses. The parameters Bmax and Kd were then determined using six different evaluation techniques, four linear and two non-linear. It is concluded that a non-linear evaluation gives more reliable results, especially when errors are large. Furthermore, an inevitable correlation between Bmax and Kd regardless of evaluation technique results in possible misinterpretations of simultaneous changes in both parameters. PMID- 1523192 TI - Recent developments in peptide drug delivery to the brain. AB - Peptide-based therapeutics are highly water-soluble compounds that do not readily enter brain from blood owing to poor transport through the brain capillary endothelial wall, i.e., the blood-brain barrier (BBB). Strategies available for peptide drug delivery to brain include: (a) neurosurgical-based (intraventricular drug infusion, hyperosmotic opening of the BBB); (b) pharmacological-based (peptide lipidization, liposomes); and (c) physiological-based (biochemical opening of the BBB, chimeric peptides). Chimeric peptides are formed by the covalent coupling of a pharmaceutical peptide (that is normally not transported through the BBB) to a brain transport vector that undergoes absorptive-mediated or receptor-mediated transcytosis through the BBB. The most efficient brain transport vector known to date is a monoclonal antibody to the transferrin receptor, and this vector achieves a brain volume of distribution approximately 18-fold greater than the plasma space by 5 hr after a single intravenous injection of antibody. The chimeric peptides are formed generally with chemical based linkers. However, avidin/biotin-based linkers allow for high yield coupling of drug to vector, and for the release of biologically-active peptide following cleavage of the chimeric peptide linker. These strategies may also be used for the delivery of antisense oligonucleotide-based therapeutics to brain. In conclusion, the development of efficacious neuropharmaceuticals in the future will require the development of both drug delivery and drug discovery strategies that operate in parallel. PMID- 1523194 TI - Active and passive electrical properties of isolated canine cardiac Purkinje fibers under conditions simulating ischaemia: effect of diltiazem. AB - The effect of a calcium channel blocker diltiazem on the electrical properties of canine Purkinje fibers superfused in a milieu similar to that occurring in acute myocardial ischaemia was studied. Action potential parameters, passive electrical properties, and conduction velocity were measured using conventional microelectrode techniques. Superfusion with glucose-free Tyrode's solution containing 9 mM K+, gassed with 100% N2 at pH = 6.5 ('ischemic solution') significantly reduced the maximal diastolic potential, action potential duration, maximal upstroke velocity, conduction velocity and length constant, while input resistance and longitudinal resistance were elevated and membrane resistance remained unchanged. Diltiazem (1 microM) alone reduced only the action potential duration, while all other parameters were unaffected. Pretreatment with diltiazem did not fully prevent the effects of ischemic superfusion; however, the ischaemia induced decrease in length constant was not significant in the presence of diltiazem. In addition, the increase in longitudinal resistance during ischaemia was significantly reduced following diltiazem pretreatment. This decrease in longitudinal resistance may contribute to the improvement of ischaemia-induced conduction delay observed in intact animals and may be related to a reduction of ischaemia-induced increase in intracellular free Ca2+. PMID- 1523195 TI - Effects of hydrocarbons on transformation and intercellular communication in Syrian hamster embryo cells. AB - The ability of 18 different hydrocarbons to induce and promote morphological transformation and to inhibit intercellular communication in primary Syrian hamster embryo cells in culture have been studied. The compounds were: the n alkanes octane, nonane, decane, undecane, dodecane and tridecane; the iso-alkanes 2-methylheptane, 2-methyloctane and 2-methylnonane; the naphthenes 1,2 dimethylcyclohexane, 1,2,4-trimethylcyclohexane and tert-butylcyclohexane; the aromates 1,2-dimethylbenzene, 1,2,4-trimetylbenzene and tert-butylbenzene; and the alkenes 1-octene, 1-nonene and 1-decene. None of the hydrocarbons induced morphological transformation of Syrian hamster embryo cells. When the hydrocarbons were incubated together with benzo(a)pyrene, enhancement of the transformation frequency was observed for the naphthene 1,2-dimethylcyclohexane and the iso-alkanes 2-methylheptane and 2-methyloctane. None of the n-alkanes, alkenes or aromates enhanced the transformation frequency induced by benzo(a)pyrene. The alkane tridecane and the iso-alkanes 2-methyloctane and 2 methylnonane reduced intercellular communication in the primary Syrian hamster embryo cells. PMID- 1523196 TI - Supersensitivity to the antinociceptive effect of a 5-HT1 receptor agonist after lesion of raphe-spinal serotonergic neurones. AB - The actions of the 5-hydroxytryptamine type-1B (5-HT1) receptor agonist 1(m chlorophenyl)piperazine (mCPP) on response latencies in the tail-flick test and tail skin temperature were examined in mice after pretreatment with the 5-HT neurotoxin, 5,6-dihydroxytryptamine (5,6-DHT). All the compounds were given intrathecally. The level of 5-HT in spinal cord was reduced by 79% 4 days after intrathecal injection of 5,6-DHT (10 micrograms). There was a significant relationship between the tail-flick latency and tail skin temperature, and the reduced baseline tail-flick latencies induced by 5,6-DHT were non-significant after the change in skin temperature was taken into account. Intrathecal mCPP (5 micrograms) significantly increased the tail-flick latency and significantly reduced the tail skin temperature in 5,6-DHT pretreated animals when compared to control animals. These differences in tail-flick latencies could not be explained by alterations in skin temperature. The results provide evidence that neurotoxic lesion of descending 5-HT pathways induces supersensitivity to the antinociceptive effect of 5-HT1 receptor stimulation. PMID- 1523197 TI - Effects of prostanoids and indomethacin on isolated smooth muscle from the human lower oesophagus. AB - Smooth muscle strips representing the longitudinal and the circular muscle layers of the oesophageal body and the oesophagogastric junction of the human oesophagus were mounted in organ baths and isometric tension recorded. Transmural field stimulation was applied to strips from both layers of the oesophageal body and to strips from the longitudinal muscle layer of the oesophagogastric junction. This resulted in contractions after cessation of the stimulus train in circular muscle, and in contractions during stimulation in longitudinal muscle preparations. Indomethacin lowered active tension in strips from the circular muscle layer of the oesophagogastric junction, and decreased responses to transmural field stimulation in all strips from the longitudinal muscle layer. The response to transmural field stimulation was increased in strips from the circular muscle layer of the oesophageal body, suggesting an inhibitory function of endogenous prostanoids in this muscle layer. Prostaglandin (PG) F2 alpha and the thromboxane A2 mimic U-46619 increased the responses to transmural field stimulation in all muscle types and the active tension in circular muscle from the oesophagogastric junction. PGE1 and PGE2 increased the responses to transmural field stimulation strips from the longitudinal muscle layer. In circular muscle strips from the oesophageal body responses to transmural field stimulation were inhibited. PGE1 decreased active tension in circular muscle strips from the oesophagogastric junction, whereas PGE2 produced inconsistent effects. These results suggest a role of prostanoids in the regulation of neuromuscular function in the human lower oesophagus. Moreover, exogenous prostaglandins may modulate oesophageal motor function. PMID- 1523199 TI - Collaborative studies on chorion villus sampling in North America. PMID- 1523198 TI - The XXII annual Nordic meeting on Biological Alcohol Research. Vaerlose, Denmark, October 9-11, 1992. Abstracts. PMID- 1523200 TI - Prenatal diagnosis. PMID- 1523201 TI - Cytogenetic results from the U.S. Collaborative Study on CVS. AB - Cytogenetic data are presented for 11,473 chorionic villus sampling (CVS) procedures from nine centres in the U.S. NICHD collaborative study. A successful cytogenetic diagnosis was obtained in 99.7 per cent of cases, with data obtained from the direct method only (26 per cent), culture method only (42 per cent), or a combination of both (32 per cent). A total of 1.1 per cent of patients had a second CVS or amniocentesis procedure for reasons related to the cytogenetic diagnostic procedure, including laboratory failures (27 cases), maternal cell contamination (4 cases), or mosaic or ambiguous cytogenetic results (98 cases). There were no diagnostic errors involving trisomies for chromosomes 21, 18, and 13. For sex chromosome aneuploidies, one patient terminated her pregnancy on the basis of non-mosaic 47,XXX in the direct method prior to the availability of results from cultured cells. Subsequent analysis of the CVS cultures and fetal tissues showed only normal female cells. Other false-positive predictions involving non-mosaic aneuploidies (n = 13) were observed in the direct or culture method, but these cases involved rare aneuploidies: four cases of tetraploidy, two cases of trisomy 7, and one case each of trisomies 3, 8, 11, 15, 16, 20, and 22. This indicates that rare aneuploidies observed in the direct or culture method should be subjected to follow-up by amniocentesis. Two cases of unbalanced structural abnormalities detected in the direct method were not confirmed in cultured CVS or amniotic fluid. In addition, one structural rearrangement was misinterpreted as unbalanced from the direct method, leading to pregnancy termination prior to results from cultured cells showing a balanced, inherited translocation. False-negative results (n = 8) were observed only in the direct method, including one non-mosaic fetal abnormality (trisomy 18) detected by the culture method and seven cases of fetal mosaicism (all detected by the culture method). Mosaicism was observed in 0.8 per cent of all cases, while pseudomosaicism (including single trisomic cells) was observed in 1.6 per cent of cases. Mosaicism was observed with equal frequency in the direct and culture methods, but was confirmed as fetal mosaicism more often in cases from the culture method (24 per cent) than in cases from the direct method (10 per cent). The overall rate of maternal cell contamination was 1.8 per cent for the culture method, but there was only one case of incorrect sex prediction due to complete maternal cell contamination which resulted in the birth of a normal male.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1523202 TI - Chorionic mosaicism: association with fetal loss but not with adverse perinatal outcome. AB - Cytogenetic data from the United States NICHD collaborative study of chorionic villus sampling (CVS) were used to evaluate the clinical significance of chorionic mosaicism. The 10,754 patients with normal cytogenetic results were compared with 108 patients (1.0 per cent) with placental mosaicism and 181 patients (1.6 per cent) with pseudo-mosaicism. Of the pregnancies intended to continue, the pregnancy loss rate was significantly greater in patients with placental mosaicism than in the cytogenetically normal cohort (8.6 vs. 3.4 per cent, p less than 0.05). However, there was no difference in the frequencies of abruptio placenta, preterm labour or delivery, small-for-gestational-age newborns, pregnancy-induced hypertension, or neonates with Apgar scores less than 7. PMID- 1523203 TI - First-trimester biochemical and molecular diagnoses using chorionic villi: high accuracy in the U.S. collaborative study. AB - The accuracy of biochemical and molecular prenatal diagnoses using chorionic villi as the fetal source was assessed by seven centres participating in the NICHD collaborative study on the safety and accuracy of chorionic villus sampling (CVS) and amniocentesis. Of 601 pregnancies studied, biochemical methods were used to determine the diagnosis in 283 fetuses at risk for 35 different metabolic disorders. Fifteen different lysosomal storage diseases accounted for 81 per cent of the biochemical prenatal diagnoses performed, with 57 per cent of these pregnancies at risk for Tay-Sachs disease. No errors were made in the biochemical diagnoses that predicted affected or unaffected fetuses. However, the diagnoses of certain disorders (e.g., mucopolysacchariodosis type IH, metachromatic leukodystrophy, and Krabbe disease) occasionally required confirmatory studies in cultured amniocytes because the enzyme results were inconclusive in direct and/or cultured villi or due to the presence of a pseudodeficiency allele. Of these, only the diagnosis of a fetus at risk for Krabbe disease remained inconclusive after special studies to discriminate between mutant and pseudo-deficiency alleles. Recombinant DNA techniques were used to predict the diagnosis of 318 fetuses at risk for 16 different disorders in which the defective disease gene could be detected either directly or by linkage analysis to a nearby polymorphic marker. Of these, 32 per cent were for haemoglobinopathies, 25 per cent for cystic fibrosis, 24 per cent for Duchenne or Becker muscular dystrophy, and 7 per cent for haemophilias. Pregnancies at risk for known disorders with specific molecular lesions (e.g., sickle cell disease) were accurately diagnosed in direct and/or cultured villi. Diagnoses requiring analyses with closely linked polymorphic markers were occasionally uniformative or inconclusive. Maternal contamination was not reported in any biochemical or molecular-based diagnosis. These studies document the high accuracy and rapidity of both biochemical and mutation-specific prenatal diagnoses with direct and cultured chorionic villi. PMID- 1523204 TI - Risk factors associated with transcervical CVS losses. AB - Factors found to be associated with pregnancy loss after transcervical CVS were race (higher for non-white), history of spontaneous abortion, unplanned pregnancy, history of spotting or bleeding during the pregnancy prior to CVS, and placental position (higher for fundal or lateral locations). Whether the increase in loss risk is due to the factor, per se, or the factor plus the CVS cannot be determined due to the lack of appropriate control data. PMID- 1523205 TI - The risk and efficacy of chorionic villus sampling in multiple gestations. AB - Chorionic villus sampling (CVS) in the first trimester of pregnancy provides a safe and effective method for the early prenatal diagnosis of cytogenetic abnormalities in multiple gestations. In this multicentre study involving 126 twin and 2 triplet gestations primarily at risk because of advanced maternal age, the overall success rate of obtaining an adequate villus sample from each fetus was 99.2 per cent. For women of advanced maternal age, the rate of combined losses of chromosomally normal fetuses due to spontaneous abortion, stillbirths, and neonatal deaths was 5.0 per cent, compared with a 4.0 per cent total loss rate following CVS in singleton pregnancies derived from the same population (Rhoads et al., 1989). There was a 100 per cent success rate in obtaining a cytogenetic analysis; a cytogenetic abnormality was present in five of the multiple gestations (3.9 per cent) and involved seven fetuses (2.7 per cent). There were no diagnostic errors and no cases of normal cytogenetic diagnosis followed by the birth of a cytogenetically abnormal newborn. Based on cases of XX/XY admixture, cell contamination derived either from maternal decidua or the other twin occurred in 6 of 256 samples (2.3 per cent), giving an overall estimate of the frequency of cell contamination of 4.6 per cent; these cases did not present a diagnostic problem. However, there were two cases (0.8 per cent) in which the fetal sex was incorrect, due either to complete maternal cell contamination or to the possibility that in error one twin was sampled twice. PMID- 1523206 TI - Canadian multicentre randomized clinical trial of chorion villus sampling and amniocentesis. Final report. PMID- 1523207 TI - Canadian multicenter randomized clinical trial of chorion villus sampling and amniocentesis. Detailed obstetrical procedures and results. PMID- 1523208 TI - Canadian multicenter randomized clinical trial of chorion villus sampling and amniocentesis. Fetal and neonatal losses. PMID- 1523209 TI - Canadian multicenter randomized clinical trial of chorion villus sampling and amniocentesis. Surviving births. PMID- 1523210 TI - Canadian multicenter randomized clinical trial of chorion villus sampling and amniocentesis. List of all cytogenetic abnormalities detected. PMID- 1523211 TI - Canadian multicenter randomized clinical trial of chorion villus sampling and amniocentesis. chromosome mosaicism in CVS and amniocentesis samples. AB - Data on 1040 chorionic villus and 969 amniotic fluid samples were collected from women studied in the Canadian Multicentre Randomized Clinical Trial of Chorion Villus Sampling and Amniocentesis. Cytogenetic results were obtained from 98.0 per cent of chorionic villus samples and from 99.9 per cent of amniotic fluid samples. Level I mosaicism (a single cell with an abnormal karyotype) occurred frequently in both chorionic villus and amniotic fluid samples and appeared to have no clinical significance. Level II mosaicism occurred in 0.9 per cent of CVS mesenchyme and 1.5 per cent of amniotic fluid cultures and in general was not perceived to be of sufficient concern to warrant cytogenetic follow-up studies. Level III mosaicism was reported in 18 CVS cases (15 cytotrophoblast, 1 mesenchyme, and 2 with both cell methods) and in one amniotic fluid case. In all cases but one (fetus with trisomy 18), level III mosaicism was confined to the placenta. Maternal cell contamination occurring with a frequency of 6.4 per cent in the mesenchyme analyses was a concern. This study supports the final report of the Canadian Multicentre Randomized Clinical Trial of Chorion Villus Sampling and Amniocentesis. Cytogenetic analysis of chorionic villus samples appears to be an acceptable alternative to the analysis of amniotic fluid samples. However, because of mosaicism and maternal cell contamination concerns, the examination of both cytotrophoblast preparations and mesenchyme cultures from chorionic villus samples is recommended. PMID- 1523212 TI - Studies of placental pathology in randomized women undergoing either amniocentesis or CVS. PMID- 1523213 TI - Familial chromosomal aberrations and metabolic disorders. PMID- 1523214 TI - Effect of ryanodine on mitochondrial respiration. AB - Ryanodine is a pharmacological agent that stimulates calcium leakage into the cytoplasm resulting in an increase in tension. In skeletal muscle, ryanodine acts primarily on the sarcoplasmic reticulum whereas in smooth muscle, the sites of action are less clear. Visually, the increase in tension is slow and the time course can be mimicked by mitochondrial poisoning and the resultant leak of mitochondrial calcium into the cytoplasm. Although it has been reported that ryanodine has no effect on calcium flow into or from mitochondria, the effect of ryanodine on mitochondrial oxidative function was not studied. In the current investigation direct measurements of the effect of ryanodine on mitochondrial oxygen utilization were made. The results demonstrate that ryanodine, even at high concentrations, has no effect (stimulatory or inhibitory) on mitochondrial oxidation. PMID- 1523215 TI - Cytoprotective action of beraprost sodium against peroxide-induced damage in vascular endothelial cells. AB - Using a peroxide-injured endothelial cell model, beraprost sodium (beraprost) was tested in relation to the action to protect against the damage of vascular endothelial cells employing the viability of the cells and change in lipid peroxides as the indicators. At a concentration of 1-3 mumol/l or higher, beraprost significantly inhibited the decrease in viability of the cells and the increase in lipid peroxides level caused by t-butyl hydroperoxide or 15 hydroperoxy-5,8,11,13-eicosatetraenoic acid. When similar tests were conducted with prostaglandin I2, its inhibiting action was equal to or slightly weaker than that of beraprost unlike PGE1 and PGD2. This action of beraprost in inhibiting cell damage caused by peroxides suggests that beraprost may be useful for protecting cells from damage due to ischemic diseases. PMID- 1523216 TI - Potassium channel activators cromakalim and celikalim (WAY-120,491) fail to decrease myocardial infarct size in the anesthetized canine. AB - The cardioprotective effects of the K channel activator drugs celikalim (WAY 120,491) and cromakalim were studied in a canine model of myocardial infarction consisting of 90 min of ischemia and 5 h of reperfusion. Intracoronary infusion of cromakalim and celikalim at 0.2 microgram/kg/min beginning 10 min before occlusion of the left circumflex coronary artery and continuing throughout the duration of the reperfusion period appeared to exacerbate ischemic injury. Infarct size (percent of risk area) was 27.7 +/- 5.6% in vehicle control animals (n = 5), 40.3 +/- 6.2% for cromakalim (n = 5) and 55.7 +/- 6.4% (p less than 0.05 vs. vehicle) for celikalim-treated animals (n = 5). When these compounds were administered intravenously, using doses shown to increase total coronary flow in nonoccluded control animals, no exacerbation of ischemic injury was observed. Anatomic infarct size was 32.8 +/- 7.1% for vehicle animals (n = 5) and 32.6 +/- 13.3 and 30.9 +/- 9.8% for cromakalim- (n = 6) and celikalim-treated (n = 5) animals, respectively. Intravenous diltiazem decreased myocardial infarct size to 16.3 +/- 7.3% (n = 5) of area at risk (p = NS vs. vehicle). The anatomic area at risk was similar in all three treatment groups, and no significant differences in rate-pressure product were observed. Results of this study suggest that K-channel activating drugs such as cromakalim and celikalim may not be effective agents in the acute therapeutic management of myocardial ischemic injury. PMID- 1523217 TI - Cardiovascular effects of acetaldehyde in pithed rats. AB - The influence of acetaldehyde (30 mg/kg i.v.) on blood pressure and heart rate in anesthetized and pithed rats was studied. In anesthetized rats we observed a small increase, and a subsequent considerable decrease in mean blood pressure. The latter did not occur in pithed rats. Stimulation of the circulatory system in anesthetized and in pithed rats was completely abolished by administration of phentolamine or reserpine. Both in anesthetized and in pithed rats acetaldehyde caused an increase in heart rate which was inhibited in animals treated earlier with propranolol or reserpine. Our results demonstrated that besides its peripheral action, acetaldehyde exerts central effects which cause severe hypotension. PMID- 1523218 TI - Cytosol-free calcium concentration in single bladder smooth muscle cells from normal and diabetic rats. AB - The effect of diabetes mellitus on intracellular calcium concentration was measured in single rat bladder smooth muscle cells using the fluorescent calcium indicator dye fura-2 AM. Techniques were developed for isolation and short-term culture of rat bladder smooth muscle cells. Cytosol-free calcium concentrations were measured at rest and during carbachol stimulation. Peak intracellular calcium concentration, rate of increase in intracellular calcium concentration and the integral of accumulation of intracellular calcium were determined. The techniques used to isolate and culture bladder smooth muscle cells produced live, physiologically responsive cells. Resting intracellular free calcium levels and were similar in control and diabetic cells. Both control and diabetic cells responded to carbachol stimulation. No significant differences between these cells were noted in peak calcium concentrations, rate of response or integral of response, but standard errors were large. Two patterns of intracellular response to carbachol stimulation were identified, and may explain the large variability in intracellular calcium response to carbachol stimulation. PMID- 1523219 TI - Vomeronasal and/or olfactory mediation of ultrasonic calling and scent marking by female golden hamsters. AB - The role of the olfactory and vomeronasal systems in mediating odor-stimulated ultrasonic calling, flank marking, and vaginal marking by female hamsters was investigated by selective lesions of either system. Removal of the vomeronasal organ resulted in reduced frequencies of ultrasonic calling by estrous and nonestrous females in response to conspecific odors but it had no influence on either scent marking behavior during the same tests. When tested immediately after separation from a male, ultrasonic calling was not reduced by vomeronasal removal, indicating that such surgery does not cause deficits in calling ability and that the vomeronasal organ specifically mediates odor-stimulated calling. Zinc sulfate treatment of the olfactory mucosa led to reduction in the frequency of ultrasonic calling, flank marking, and vaginal marking in response to conspecific odors. Females' ability to discover buried food was also impaired by this treatment. Thus, the stimulation of both scent marking behaviors due to the perception of conspecific odors appears to be mediated primarily by the olfactory system, whereas stimulation of ultrasonic calling is mediated by both olfactory and vomeronasal systems. PMID- 1523220 TI - Sex difference in blood pressure of spontaneously hypertensive rats influenced by perinatal NaCl exposure. AB - Our prior study showed that the basal blood pressure level and pressor response to peripheral angiotensin II of adult Sprague-Dawley rats were enhanced by perinatal exposure to a high NaCl diet. The purpose of the present study was to assess further the relationship between NaCl-sensitivity of blood pressure and perinatal NaCl exposure. We tested the hypothesis that the basal blood pressure level and pressor responses to angiotensin II could be increased by perinatal exposure to high NaCl in NaCl-resistant spontaneously hypertensive rats (SHR-R). Adult female SHR-R were maintained on a diet containing either basal 1% or high 8% NaCl throughout pregnancy and lactation. The offspring were continued on these same diets to 30 days postpartum. Thereafter, all offspring were maintained on a diet containing 1% NaCl. After being adapted to restraint, systolic blood pressure was measured indirectly by the tail-cuff procedure when the rats were 30, 44, and 58 days of age. Subsequently, baseline mean arterial pressure (MAP) and pressor responses to intravenous administration of angiotensin II (20, 40, 80, and 120 ng/kg body weight) were obtained from the catheterized femoral artery in conscious unrestrained rats. The MAP levels of adult female SHR-R exposed perinatally to 8% NaCl were significantly greater than those of females exposed to 1% NaCl. This elevated blood pressure was accompanied by an elevation in plasma osmolality. Perinatal exposure to 8% NaCl did not raise the blood pressure and plasma osmolality levels of adult male SHR-R, but did enhance pressor responses to angiotensin II.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1523221 TI - Diet-induced thermogenesis and cumulative food intake curves as a function of familiarity with food and dietary restraint in humans. AB - Cumulative food intake curves and diet-induced thermogenesis were recorded in women during four-course solid-food lunches, consisting of familiar and unfamiliar food, offered in ad lib or restricted portions, in order to assess a possible relation between eating behaviour on the one hand and a reflection of internal processes and subject characteristics on the other. The subjects were characterized as normal weight restrained, normal weight unrestrained, and overweight restrained. A negative relation was found between degree of restraint and deceleration of the cumulative food intake curve during the ad lib courses of any menu, and between degree of restraint and diet-induced thermogenesis (p less than 0.001). Consequently, a positive relation was found between deceleration of the cumulative food intake curves during the ad lib courses of any menu and diet induced thermogenesis (p less than 0.001). Diet-induced thermogenesis during the first serving of a meal consisting of unfamiliar food was significantly higher in all groups than during the other two times, when meals consisting of more familiar food were served (+0.98%; 0.71%, p less than 0.05). PMID- 1523222 TI - Social separation and reunion affects immune system in juvenile rhesus monkeys. AB - Removal of juvenile rhesus monkeys from their natal social group to indoor individual caging resulted in increased basal cortisol secretion and significant decrements in the frequency of lymphoid subpopulations. Fourteen juvenile rhesus monkeys, which had never been removed from the group, were studied. Baseline immune and cortisol measurements were obtained before seven of the subjects were removed from social housing to standard individual cages. The remaining seven subjects, matched for age, sex, weight, and rank, remained in the social group throughout the study serving as controls. Blood samples were taken 24 hours after removal of the test subjects from the group and at specific intervals thereafter through 11 weeks. At 24 hours after the separation test subjects showed a significant increase in basal cortisol levels (40%) and a significant decrease in several immune parameters, with absolute numbers of total T cells declining 72 +/ 12%. Significant group differences in immune parameters persisted through 11 weeks. Eighteen weeks following removal, the test subjects were returned to the group which produced a cortisol rise in both test and controls at the 24-hour postreturn sample. Although there were no group differences in the frequency of lymphoid subsets 24 hours after return, some test subjects showed marked decrements which were inversely related to cortisol and were predicted by behavioral events. These data demonstrate that the removal of naive juvenile rhesus monkeys from their natal social group to individual indoor caging is a potent psychosocial stressor and that the behavioral interactions which characterize the return of the individual subjects to the natal group may predict physiological response. PMID- 1523223 TI - Postnatal deficiency of omega-3 fatty acids in monkeys: fluid intake and urine concentration. AB - Previous studies demonstrated increased fluid intake in rhesus monkeys exposed to combined prenatal and long-term postnatal (PRE+POST) dietary deficiency of omega 3 fatty acids. Here we determined the effect of dietary deficiency in omega-3 fatty acids occurring only prenatally (PRE) or only postnatally (POST). Water intake over 24 hours, water intake in 15-minute tests, and excretion of combined urine and feces over 24 hours were all about twice as great in POST as in PRE monkeys. Neither group preferred or avoided salt solutions compared to water in two-bottle tests. Serum electrolytes, total protein, and glucose were within the normal range, and both groups concentrated urine when deprived of water. Levels of all omega-3 fatty acids in red blood cells were greatly depressed in POST monkeys, while levels of omega-6 fatty acids were elevated or unchanged. These results confirm the effects of PRE+POST deficiency on fluid intake and demonstrate that postnatal deficiency by itself is sufficient for the effects. PMID- 1523224 TI - Prostaglandins E2 and D2 have little effect on rabbit sleep. AB - Prostaglandins (PGs) are hypothesized to be involved in sleep regulation; PGE2 and PGD2 are major PGs in the hypothalamus of many species and are proposed to reciprocally promote wakefulness and sleep respectively. PGD2 and PGE2 are also major PGs in rabbit cerebrospinal fluid, yet their effects on rabbit sleep have not heretofore been systematically investigated. We report here that a bolus injection of PGE2 into a lateral cerebral ventricle induces dose-dependent fevers and transient sleep responses in rabbits. PGE2 induces a suppression of sleep of 24 min duration. In contrast, PGD2, across a wide range of doses (0.25-500 nmol) failed to alter sleep; however, at the highest dose it induced fever. We conclude that if PGs are involved in sleep regulation, a chronic stimulation of their production by other sleep factors is necessary. PMID- 1523225 TI - Cocaine-exposed newborns show an exaggerated sucking response to sucrose. AB - The sucking responses of 16 newborn infants exposed to cocaine just prior to birth and 16 control newborns were recorded when offered a fluidless sucrose flavored nipple and a comparable nonsweet nipple. Cocaine-exposed infants showed a significantly greater preference for sweet taste: Compared with control infants, the cocaine group sucked more frequently when offered the sweet nipple and less frequently when presented with the nonsweet nipple. This heightened response to sweet stimulation might reflect (i) a coping mechanism for the perinatal distress of intrauterine cocaine-exposure since sweet taste appears to alleviate distress via an opioid mechanism; and/or (ii) altered dopaminergic activity in a common neuronal pathway that mediates the rewarding aspects of both cocaine and sweet taste. PMID- 1523226 TI - The effects of anticholinergic drugs on delayed time discrimination performance in rats. AB - To investigate the effects of the muscarinic antagonist scopolamine and the nicotinic antagonist mecamylamine on time discrimination and short-term memory, rats were trained on a delayed conditional time discrimination task until performance stabilized. In a two-lever operant chamber, pressing one lever was correct after the presentation of a stimulus light for 2 seconds (SD short); and pressing the other lever was correct after presentation of a stimulus light for 8 seconds (SD long). Scopolamine (0.06 mg, 0.25 mg, and 1.0 mg/kg) attenuated performance in a dose-dependent manner. Furthermore, the drug decreased nose pokes (an activity necessary to trigger the presentation of the discriminative stimuli and the presentation of the response levers), and increased response delay (time from opportunity to lever press to actual lever press). Performance attenuating effects of mecamylamine in the time discrimination task did not appear unless high doses (8 mg/kg) of the drug were given. With increasing delays between 0 and 8 seconds, animals injected with saline developed a bias towards reporting the occurrence of the SD long, independent of the actual stimulus presented. A reversal of this bias was seen in animals injected with scopolamine; they more often reported the occurrence of the SD short. Our results support a role for muscarinic receptors in discrimination learning, attention, and time estimation. PMID- 1523227 TI - Reactivity to written mental arithmetic: effects of exercise lay-off and habituation. AB - The present study examined (i) the effects of exercise lay-off on heart rate (HR) and subjective response to mental stress in 24 individuals highly committed to exercise, and (ii) psychophysiological reactivity to a challenging written mental arithmetic with subjectively controlled difficulty level. Subjects were tested on two occasions one week apart. Exercise withdrawal did not influence psychophysiological stress response. Second exposure to the mental arithmetic resulted in significantly lower HR response, due to habituation; higher pretask resting HR, due to anticipation of performance; and later onset in HR recovery. No changes in task performance and subjective measures were observed from session one to session two, indicating that habituation is rather a physiological than behavioral phenomenon. While these findings do not strengthen the link between exercise and stress response, they demonstrate the significant mediatory roles of habituation and anticipation in laboratory studies employing a test-retest design. PMID- 1523228 TI - A system for studying the microstructure of ingestive behavior in mice. AB - A system for long-term monitoring of mouse eating and drinking behavior with 6-s resolution is described. The apparatus utilizes infrared beams to monitor activity at a single feeding port and electronic contact detector circuitry to record individual licks at two drinking ports. Eight SWR/J mice were monitored using this system and data from the last day of testing with food and water were analyzed. Mice ate an average of 4.54 +/- 0.40 g of powdered food and drank an average of 5.81 +/- 0.65 ml of water. Mice had an average of 36.25 +/- 3.96 food bouts and 32.25 +/- 7.56 water bouts lasting 3.00 +/- 0.48 and 0.88 +/- 0.35 min, respectively. Information regarding the temporal association between eating and drinking and the circadian patterns of ingestion was provided, utilizing customized software that augments the system. Important implications for the use of mice in ingestion pattern research are discussed. PMID- 1523229 TI - Motor abnormalities in lurcher mutant mice. AB - Lurcher mutants had deficits in equilibrium in the coat-hanger and grid tests but not the wooden beam test. Although the mutants had less hole-pokes when confronted with small holes in most conditions, they had more hole-pokes with larger holes, demonstrating perseverative behavior. There was no decrease in rearing responses. These results indicate that in spite of cerebellar degeneration and ataxia, lurcher mutants are not impaired in all tests measuring motor function. PMID- 1523230 TI - Neonatal catecholaminergic influence on behaviour and sexual hormones. AB - There is evidence of a sexually dimorphic effect of serotonin administration during the critical period of sexual differentiation on gonadal hormone secretion in adulthood. To investigate the possible involvement of catecholamines on these mechanisms, we have injected dopamine or noradrenaline intraventricularly into neonatal male and female rats to examine the influence, during the critical period, of this single treatment on the adulthood. Gonadal sex hormone contents, sexually dimorphic behaviours, and catecholaminergic distribution in hypothalamic and extrahypothalamic areas were studied. Both catecholaminergic treatments in females resulted in a reduced striatal dopaminergic activity and an increase in the hypothalamic noradrenergic ratio, while a reduction in the open field activity occurred in the same groups. These results suggest the possible involvement of striatal dopamine and hypothalamic noradrenaline in the differentiation of exploratory activity in females. A reduction in copulatory behaviour was shown in adults of both sexes after neonatal dopaminergic administration, but gonadal hormone levels were not affected in the same way. This indicates the existence of different facets of sexual differentiation, with striatal dopamine and hypothalamic noradrenaline playing important roles in neurobehavioural differentiation. PMID- 1523231 TI - Foraging for macronutrients: effects of protein availability and abundance. AB - A laboratory simulation of foraging required rats to search for opportunities to obtain meals of pure-macronutrient foods (separate sources of carbohydrate, fat, and protein). Reductions in protein availability (increases in the cost of procuring protein meals) and reductions in protein abundance (decreases in the likelihood of encountering protein meal opportunities) were examined in separate phases. Rats foraged selectively, composing high-fat, adequate-protein diets; they tended to alternate between protein and nonprotein meals when protein was accessible. When protein became less available or relatively less abundant, meal patterns changed, and the proportional intake of protein fell. The tactic of shifting relative nutrient intake was used to a greater extent than the tactic of increasing foraging behavior. The foraging constraints revealed a flexible nutritional strategy that balanced responses to internal and external demands. PMID- 1523232 TI - Somatosensory control of the onset and retention of maternal responsiveness in primiparous Sprague-Dawley rats. AB - The role of perioral and ventral-trunk somatosensory stimulation from pups mediating the initial expression of maternal behavior and its long-term retention 8 days later, was investigated. Six groups of female rats were permitted to physically interact with four 1-5-day-old foster pups for 1 h, 36 h after Cesarean delivery on gestation day 21. Prior to this maternal experience, dams were subjected to: reduced cutaneous rostral snout sensitivity (anaptia) by injection of lidocaine into the mystacial pads; reduced ventral-trunk sensations by occlusion of the entire ventrum with a full spandex jacket; both manipulations; or control manipulations. Additional groups of females not receiving a maternal experience (inexperienced) also received the somatosensory deprivation or control manipulations. During retention testing, rats in the singly manipulated experienced groups exhibited reduced latencies to become maternal in comparison to their inexperienced counterparts (approximately 3 days vs. 8 days). However, rats previously rendered both anaptic and ventrally occluded responded like inexperienced rats in showing a long latency to become maternal (8 days). Thus, reduction of either perioral or ventral somatosensory contact from pups did not block the maternal experience effect, but reduction of both of these inputs did. PMID- 1523233 TI - Choice behavior of fornix-damaged rats in radial maze error-free situations and subsequent learning. AB - Fornix-damaged, sham-operated, and control rats were placed in a radial eight-arm maze for fixed series of runs with either a 0% or a 100% reinforcement schedule in order to study their choice behavior independently from any learning problem. Subsequently, the ability to learn the radial maze task was examined as a function of the exploratory patterns developed in each error-free situation. The results showed that the continuous absence or presence of food in the radial maze induced two distinct models of exploration in sham-operated and control rats: choice alternation in the absence of food and perseveration in the presence of food. Conversely, this dichotomy did not occur in fornix-damaged rats that run approximately the same number of paths in both error-free situations, but made fewer different path choices in the 0% reinforcement condition and more different path choices in the 100% reinforcement condition than controls. When submitted to the radial maze task, a positive transfer was observed in all groups from the error-free situation in which the rats run more different paths: from the 0% reinforcement situation for controls and from the 100% reinforcement situation for the lesioned rats. These data indicate that damaging the septo-hippocampal pathway modifies spontaneous choice behavior through a different response to specific reinforcement programs but does not prevent the memorization and the transfer of information from error-free to learning situations. PMID- 1523234 TI - Control of ventilation in androgenized hypogonadal male rats. AB - We have previously shown that subcutaneous administration of aspartic acid (a dicarboxylic acidic amino acid) at a dose of 580 mg/kg causes long lasting depression of ventilation in adult intact and postpubertally castrated male rats, but not in intact female rats. The purpose of the present study was to determine if hypogonadism induced by perinatal administration of testosterone propionate (TP) will alter ventilation, oxygen consumption, and the ventilatory response to aspartic acid and to hypercapnia in adult males. TP treatment resulted in adult males who had lower body, prostate, heart, and testes weights than those of control male rats. Ventilation in air and oxygen consumption were comparable between the two groups as was the ventilatory response to aspartic acid. In contrast, TP-treated rats exhibited a significantly decreased ventilatory response to hypercapnia due predominantly to lower tidal volumes compared to control animals. Aspartic acid treatment did not affect oxygen consumption in either group. Thus, TP treatment results in the development of adult male rats who, although hypogonadal, retain a male-like ventilatory response to aspartic acid, but whose response to hypercapnia is more like that of hypogonadal men and rats. PMID- 1523235 TI - Thermoregulatory responses of rhesus monkeys during spaceflight. AB - This study examines the activity, axillary temperature (T(ax)), and ankle skin temperature (Tsk) of two male Rhesus monkeys exposed to microgravity in space. The animals were flown on a Soviet biosatellite mission (COSMOS 1514). Measurements on the flight animals, as well as synchronous flight controls, were performed in the Soviet Union. Additional control studies were performed in the United States to examine the possible role of metabolic heat production in the T(ax) response observed during the spaceflight. All monkeys were exposed to a 24 h light-dark cycle (LD 16:8) throughout these studies. During weightlessness, T(ax) in both flight animals was lower than on earth. The largest difference (0.75 degree C) occurred during the night. There was a reduction in mean heart rate and Tsk during flight. This suggests a reduction in both heat loss and metabolic rate during spaceflight. Although the circadian rhythms in all variables were present during flight, some differences were noted. For example, the amplitude of the rhythms in Tsk and activity were attenuated. Furthermore, the T(ax) and activity rhythms did not have precise 24.0 hour periods and may have been externally desynchronized from the 24-h LD cycle. These data suggest a weakening of the coupling between the internal circadian pacemaker and the external LD synchronizer. PMID- 1523236 TI - The single-item meal as a measure of binge-eating behavior in patients with bulimia nervosa. AB - To determine whether the characteristics of binge eating could be observed in a single-item meal, in a laboratory, patients with bulimia nervosa and controls ate two single-item meals and two multiple-item meals. When they were instructed to binge eat, the patients ate significantly more and for a longer time on both single- and multiple-item meals than did controls. When they were instructed not to binge, intakes of the two groups did not differ. Controls, but not most of the patients, showed deceleration in their eating rate when they were asked to binge. Intakes of the single- and multiple-item meals were significantly correlated for the patients under both sets of instructions. These results are consistent with previous reports in indicating that patients with bulimia nervosa eat differently from controls and suggest that a single-item meal can be used to examine the characteristics of binge eating in patients with bulimia nervosa. PMID- 1523237 TI - The effects of amphetamine on body weight and energy expenditure. AB - Although there is evidence suggesting that, in addition to suppressing food consumption, amphetamine reduces body weight by increasing energy expenditure, there is little consistency among the few studies examining that factor. In this experiment, the effect of amphetamine on daily energy consumption, within-day body weights, and hourly measures of metabolic rate (MR) and respiration quotient (RQ) were assessed. Daytime drug injections decreased total energy consumption, produced biphasic changes over time in MR, and persistently lowered RQ values. In contrast, nighttime injections of drug had little effect on energy consumption and MR but did reduce RQ for the first 4 postinjection hours. These effects show that amphetamine effects interact with the circadian organization of behavior and suggest that rodent studies of anorectic agents have more relevance for humans if drugs are given during the night, when rats are normally awake and eating. From this study, it seems clear that amphetamine reduces body weight by altering metabolic rate and fat metabolism in rats when the drug is given during the day. PMID- 1523238 TI - The circadian rhythm of body temperature. AB - This paper reviews the literature on the circadian rhythm of body temperature (CRT). The review starts with a brief discussion of methodological procedures followed by the description of known patterns of oscillation in body temperature, including ultradian and infradian rhythms. Special sections are devoted to issues of species differences, development and aging, and the relationships between the CRT and the circadian rhythm of locomotor activity, between the CRT and the thermoregulatory system, and between the CRT and states of disease. A section on the nervous control of the CRT is followed by summary and conclusions. PMID- 1523239 TI - Oral habituation in rat pups is in the brainstem. AB - We have previously demonstrated a decremental, oral, experienced-based control of ingestion in rat pups that is potent, diet-specific, and long lasting. This control of ingestion is revealed in the decreases in mouthing responses of rat pups to repeated oral stimulation, a phenomenon that is well described as oral habituation. The present study examined the neural basis for oral habituation by examining the responses of decerebrate 10-day-old rat pups to repeated, brief infusions of a sucrose solution. Like neurologically intact pups, decerebrate pups showed distinct decreases in mouthing responses following a series of oral infusions. Thus, oral habituation is present in the hindbrain. Although intact pups demonstrated sensitization by showing increased responding to the first few stimulus presentations, decerebrates failed to show a sensitization to the stimulation. These results suggest that while the brainstem alone is sufficient for the expression of oral habituation, the forebrain also influences oral responsivity in intact animals. PMID- 1523240 TI - The effect of feeding on defecation behaviour in pigs. AB - The effect of eating on defecation behaviour was investigated in four 20-30 kg pigs. Rectal distention stimulation was performed pre- and postprandially at 10 cm from the anus with a 5 cm latex balloon. Volume was increased in steps of 10 ml up to 200 ml of air or until balloon defecation. Dependent measures were volume, rectal pressure, determined with a solid state pressure transducer inside the balloon probe, rectal compliance, and an index of distention induced contractile activity. The volume and pressure required to elicit defecation was significantly lower after feeding (p less than 0.01). Distention induced contractile activity was significantly increased near defecation threshold, but pre- and postprandial conditions were not different. There was no difference in rectal compliance pre- and postprandially. These results suggest that eating lowers defecation threshold in terms of distention volume and rectal pressure, and that these changes are not dependent on altered rectal compliance or changes in distention induced motor activity. PMID- 1523241 TI - A microwave-transparent operant chamber for rats. AB - To study the operant behavior of rats in a microwave field, an operant chamber equipped with a response lever, stimulus lights, and a feeder was constructed using polycarbonate and fiber optic material. The chamber was connected to a personal computer located outside of the microwave chamber to program the schedules of reinforcement and to collect data. The operant chamber did not interfere with the microwave field and kept the subject's body parallel to the E field for maximum absorption. PMID- 1523242 TI - Yohimbine reduces neuropathology induced by ketamine/xylazine anesthesia. AB - Ketamine, an NMDA receptor antagonist, is commonly used in combination with xylazine, an alpha 2-adrenergic receptor agonist, to induce surgical anesthesia in birds and other vertebrates. Problems associated with this anesthetic combination include impaired thermoregulation, compounded by the inability to feed while anesthesia lasts (approximately 6 h after a single dose), and the ketamine-induced vacuolization of large cortical neurons. In the zebra finch, yohimbine (an alpha 2-adrenergic receptor agonist) counters the effects of ketamine/xylazine anesthesia, speeding recovery after the surgical procedure has been completed. In addition, administration of yohimbine reduces the formation of vacuoles in large cortical neurons and in neuropil. Yohimbine administration should be considered following all procedures involving ketamine/xylazine anesthesia. PMID- 1523243 TI - The EEG of the sleep onset period in insomnia: a discriminant analysis. AB - A period of rapid change in the wave components of the electroencephalogram (EEG) marks the transition from wake to sleep. Twenty-six insomniac and 28 control nights were studied in a discriminant analysis to determine whether this transitional state is modified in any way in subjects diagnosed for psychophysiological insomnia. A discriminant function was derived based on 20 insomniac and 22 normal nights. All 42 nights were correctly classified by this function. The sleep onset period, extending on the average over about 3 minutes, was characterized essentially by the beta and delta components of the EEG signal and by an activity index given by the ratio beta/delta, measured at the temporal lobe sites. Other variables included the subject's age and the magnitude of the changes occurring in the difference between activities in the right and left hemispheres. The variables contributing most to the discrimination were the activity index and beta, especially at the transitions from wake to stage 1 and from stage 1 to stage 2. The contribution of delta to the discrimination was less, but extended further in time to include stage 2 sleep. A test on the remaining six insomniac and six control nights gave a 75% classification accuracy, thus validating the derived discriminant function. PMID- 1523244 TI - Rewarding effectiveness of caudal MFB stimulation is unaltered following DMH lesions. AB - The dorsomedial hypothalamus (DMH) has been proposed to be a major part of the neural substrate for self-stimulation of the medial forebrain bundle (MFB). In this report, rate-frequency and rate-current curves were collected from 19 rats with lesions in or around the DMH and stimulation electrodes in or near the caudal MFB. Thirteen rats with lesions of the DMH showed little or no postlesion change in the rewarding effectiveness of caudomedial MFB stimulation. Six other lesions, affecting the anterior, dorsal, and/or ventromedial hypothalamus, were also ineffective in changing rewarding effectiveness. The one lesion that was followed by a substantial decrease in rewarding effectiveness, invaded the medial MFB at the level of the lateral hypothalamus but produced little DMH damage. These data do not support the notion that neurons arising in, terminating in, or projecting through the DMH play an important role in MFB self-stimulation. PMID- 1523245 TI - Hedonic response of sucrose likers and dislikers to other gustatory stimuli. AB - The majority of individuals can be classified as sweet likers or dislikers based on their hedonic (pleasure) response to sucrose solutions of varying concentrations. Our results indicate that the sweet liker/disliker distinction generalizes to sugars other than sucrose, i.e., glucose and fructose. As well, these individual hedonic response patterns are maintained even when a flavor and color are added to sucrose solutions. However, whether one is a sweet liker or disliker does not predict hedonic response to nonsweet tastes such as salt. These results indicate that the sweet liker/disliker distinction is a robust phenomenon which appears to generalize over, but is restricted to, sweet-tasting substances. The possibility that individual differences in hedonic response may predict preferences for, and intake of, complex tastes characteristic of foods encountered in the real world, is discussed. PMID- 1523246 TI - Activity rhythms in mice. III: Stability and plasticity of rhythm characteristics in experimental and environmental conditions. AB - The expression of a biological rhythm as measured by a given descriptor results from a set of components: the subject, the measuring device, and the experimental conditions. Rhythm of activity under four experimental conditions was observed in two strains of mice: BALB/c and C57BL/6. Condition 1, the optimal normal situation, was used as a reference; condition 2 was a retest of the animals used in condition 1 twelve days later; condition 3 tested animals for a period of 3 days in a food-deprivation situation; in condition 4, animals were isolated for 2 weeks prior to testing. Data analysis of rhythm of activity in the synchronic mode is based on a series of tests in the frequency and temporal domains. Analysis of condition-linked variation in the findings indicates that these parameters are only slightly affected by the four experimental conditions. The results, however, can be hierarchized according to condition and according to the kind of parameter. The temporal parameters are more sensitive than the frequency parameters, the least sensitive being the temporo-frequential measures. Isolation produces the greatest variation in parameter magnitude. The results show that rhythm of activity is fairly stable across a number of experimental conditions, a finding that could considerably simplify experimental protocols. PMID- 1523247 TI - Hepatic vagotomy does not alter plasma insulin response to a low dose injection of glucose. AB - It has been reported that insulin concentration is altered by a hepatic vagotomy following intraperitoneal glucose injection (0.3 g/kg) resulting in supraphysiological blood glucose concentrations. On the other hand, neural activity of the hepatic vagus nerve has been shown to be substantially reduced by lower doses (0.05 g/kg intraportal; 0.1 g/kg intravenous). The present study was conducted in order to examine the role of the hepatic vagus nerve in insulin response after intraperitoneal injections of 0.1 and 0.3 g/kg of glucose. Measurements were made 5 days after section of this branch. In a first experiment, arterial glucose and insulin concentrations were not affected by the hepatic vagotomy following injections of either 0.1 or 0.3 g/kg of glucose. The same finding was also found in a second experiment in which portal glucose and insulin levels were measured after injection of 0.1 g/kg of glucose. These results suggest that large changes in neural activity are needed for the hepatic vagus nerve to influence the insulin response. PMID- 1523248 TI - Water intake during chronic preoptic infusions of osmotically active or inert solutions. AB - To further elucidate the role of the lateral preoptic area (LPO) as an osmoreceptive region, rats received chronic infusions (2 weeks) of low volumes (0.5 microliters/h) solutions of hypertonic sodium chloride (NaCl; 0.16 M), hypertonic potassium chloride (KCl; 0.16 M), hypertonic (0.32 M) or hypotonic (0.16 M) mannitol, isotonic saline, or water delivered bilaterally via subcutaneous osmotic minipumps attached to intracranial cannulae. All cannulae terminated within the anterior hypothalamus-preoptic region. Hypertonic NaCl and KCl increased water intake over preinfusion levels in the majority of animals tested. However, the effects were variable, including some sizable increases as well as decreases. Hypertonic mannitol decreased daily water intake in 15 of 25 rats and produced essentially no change in the average intake of the group. Isotonic NaCl produced smaller increases and decreases, while water produced larger changes in individual rats, but neither solution had a significant effect on the average intake of the group. None of the infusates significantly altered food intake. PMID- 1523249 TI - Burrowing and huddling in newborn porcupine: the effect on thermoregulation. AB - The newborn cape porcupine Hystrix africaeaustralis is a precocial rodent. However, the newborn spends its first 9 weeks in the burrow. Heat production (oxygen consumption--VO2) and body temperature (Tb) were measured at various ambient temperatures (Ta) in newborn (4-8-week-old) porcupines, with a body mass between 1340-1993 g during summer, from the colony kept at the Mammal Research Institute, University of Pretoria. To assess the effect of huddling, these parameters were also measured in adult pairs of porcupines (Ta = 15 and 25 degrees C) kept together in the metabolic chamber and the values were compared with those obtained from single porcupines. Overall minimal thermal conductance was calculated for newborn and paired adult porcupines. The newborn porcupines can regulate their body temperature at Tas between 10-28 degrees C. VO2 measured at lower critical point is 0.602 +/- 0.08 ml/O2/g.h. At Ta = 10 degrees C, VO2 oscillated with a characteristic amplitude and frequency, while body temperature was well regulated. Huddling decreases the lower critical point. The overall minimal thermal conductance (0.044 +/- 0.002 ml O2/g.h.1 degree C) is higher than expected from body mass, so that the young are liable to lose heat rapidly. It is well known that the newborn porcupine spends a long period in the burrow and the results of this study suggest that this may be in order to conserve energy and presumably allocate it to growth. Apart from decreasing vulnerability, delaying foraging also avoids heat loss in the newborn porcupine. PMID- 1523250 TI - Postprandial sleep and thermogenesis in normal men. AB - Twelve normal male subjects were given low- (16.77 kj/kg) and high- (54.49 kj/kg) calorie liquid carbohydrate lunch meals on 4 days, during which measures of sleep EEG, thermogenesis (heat production), core body temperature, and skin surface temperature were obtained. On 2 days subjects were required to remain awake, and on 2 days sleep was allowed. Both meals were administered in each condition. On the days that subjects were instructed to remain awake, thermogenesis was significantly greater following high-calorie meals than low-calorie meals, and both meal conditions produced levels of thermogenesis that were greater than those observed when sleep was allowed. When given the opportunity, 11 of 12 subjects slept following both low- and high-calorie meals. There was no difference between meal conditions in the total minutes or percent of stages 1, 2, 3/4, or rapid eye movement (REM) sleep following meals. However, the onset of postprandial sleep episodes was associated with the peak of the postprandial rise in thermogenesis, and the occurrence of sleep was followed by precipitous and statistically significant declines in thermogenesis and core body temperature, as well as increases in skin surface temperature. These data suggest that postprandial sleep is associated with rises in thermogenesis, and that its occurrence decreases postprandial heat production and body temperature. PMID- 1523251 TI - The influence of the stomach on crop function and feeding behavior in domestic turkeys. AB - We tested the hypotheses that motility of the crop and muscular stomach are coordinated and that the stomach exerts primary control over crop filling and emptying in domestic turkeys. Simultaneous recordings of motility of the crop, esophagus, and stomach with implanted strain gauge transducers and visual observations of food passage using image intensification radiography revealed an inverse relationship between the frequency of stomach and crop contractions. Artificially filling the stomach of a fasted turkey with a food slurry prior to feeding did not increase crop filling during the first morning meal, but it did inhibit crop emptying in fasted turkeys by markedly reducing the number of crop contractions. Artificially filling the crop of fasted turkeys prior to the first morning meal did not decrease the amount of feeding activity or the total amount of food consumed during that meal. It is suggested that meal termination is associated with the degree of inhibition of esophageal peristalsis. PMID- 1523252 TI - Effects of thyroxine on the photoperiodic control of energy balance and reproductive status in Siberian hamsters. AB - Siberian hamsters (Phodopus sungorus sungorus) exhibit a variety of seasonal responses when exposed to short days (SD), including decreases in body weight and fat, gonadal regression, and changes in several nonsteroid serum hormone concentrations. One such SD-induced hormonal change is a modest decrease in serum thyroxine (T4) concentrations. In an attempt to determine any underlying hormonal influences for the SD-induced decreases in body weight and fat, we investigated the possible role of T4 and triiodothyronine (T3). This potential paradoxical effect of these hormones on body weight and fat, as compared with most other rodent species, is not without precedent in Siberian hamsters. Specifically, changes in the gonadal steroids have opposite effects on body weight and fat in Siberian hamsters compared with laboratory rats and mice, and Syrian hamsters. SD serum thyroid hormone concentrations were elevated to long-day (LD) levels via subcutaneous T4 injections. Vehicle- and noninjected controls were included, as well as three similar LD-housed groups. Although we found a trend towards decreased T4 serum concentrations in noninjected control hamsters following 9 weeks of SD exposure, this effect did not reach statistical significance. SD housed, T4-injected hamsters had similar decreases in body, fat pad, and paired testes weights compared to the SD-housed, vehicle- and noninjected controls despite having LD-like serum T4 and T3 concentrations. Thus, no paradoxical effect of the thyroid hormones on body weight (fat) was found, nor do these hormones appear to play a role in the effects of SDs on reproductive status in this hamster species. PMID- 1523253 TI - Use of running wheels regulates the effects of the ovaries on circadian rhythms. AB - Free-running circadian rhythms in core temperature, wheel-running and general locomotor activity were studied in ovariectomized or intact female rats housed with or without access to a running wheel. No differences in the monitored parameters were found between the intact and ovariectomized rats without a wheel. In the presence of a wheel, however, the intact rats differed from those that had been ovariectomized by displaying a shorter circadian period, an increased amplitude of the temperature rhythm, and strikingly higher rates of wheel-running and general locomotor activity. After estradiol treatment, the ovariectomized rats with a wheel developed a small increase in the temperature amplitude, and also in the correlation between wheel-running and general locomotor activity; these changes were not associated with a significant increase in wheel-running or a shortening of the circadian period. We conclude that some of the differences in circadian function between intact and ovariectomized rats are due to the differential use they make of running wheels, when available, and not directly attributable to the absence or presence of gonadal steroids. PMID- 1523254 TI - Sodium preference in sheep excreting sodium predominantly in urine or faeces. AB - On moderate sodium intakes (0.5 mmol/kg/day approx.) sheep are readily divided into those that are predominantly urinary or faecal excretors of sodium (U or F sheep). Water turnover and obligatory sodium loss are lower in F sheep. In view of these differences, sodium preference was examined in U and F sheep offered water and sodium bicarbonate solutions (40 or 300 mmol/l). The F sheep took significantly more of the bicarbonate solutions and, therefore, had sodium intakes that were 51% higher on the lower concentration, 94% higher on the higher concentration. Thus, F sheep not only conserve sodium more readily when it is scarce, they select it more readily when it is available. PMID- 1523255 TI - Group size modifies the patterns and muscle carbohydrate effects of aggression in Betta splendens. AB - Aggressive encounters of previously isolated individuals were investigated in dyads and groups of five. Fights were longer and more intense when they were performed in dyads compared to fights involving five fishes. During aggressive encounters, an elevation in carbohydrate catabolism was noticed in both dyads and groups. Losing a fight resulted in a reduction in glycogen content and an increase in glycogen synthesis. Similar changes in winners did not appear; thus, the metabolic response in losers was different from that noticed in winners, both in dyads and groups. In dyadic contest winners, a marked increase in the free glucose content and glucose consumption was noticed (without changes in losers). In groups, free glucose content of the winners was not modified, while glucose consumption was enhanced both in winners and losers. Thus, the differences existing between winners and losers were greater in dyads compared to those noticed in groups. The energy cost of aggression seems to be different in dyads compared to groups of five. The rate of glucose oxidation was strongly reduced in dyads (there were no differences between winners and losers in this respect), while in groups, this parameter was not modified. PMID- 1523256 TI - Effects of thymectomy on reproductive function and behavior. AB - The effects of thymectomy in perinatal Long-Evans rat pups on their reproductive function in early adulthood were examined. Thymectomized females had decreased lordotic responsivity to estrogen, while thymectomized males exhibited differences in mount latency or postejaculatory interval; these results suggest a possible influence of the thymus on the normal development of the neural substrates of sexual behavior. Gonadal histology appeared unperturbed in rats of either sex. No statistical abnormalities in luteinizing hormone or testosterone levels were seen in male animals. Likewise, no disturbances were observed in the ability of females to exhibit normal positive feedback after estrogen and progesterone administration; negative feedback after unilateral ovariectomy (as judged by ovarian compensatory hypertrophy) was also normal. The timing of puberty was not statistically delayed in females, even though slowed growth rates were observed. A heightened surgical stress response, as judged by progesterone levels in experimental females, suggests that perinatal thymectomy may possibly alter the sensitivity of adults to stress. PMID- 1523257 TI - Pimozide mitigates excessive running in the activity-stress paradigm. AB - The present study investigated the role of dopamine in the maintenance of behaviors observed in the activity-stress paradigm. In Experiment 1, several doses (0, 0.125, 0.25, 0.50, and 1.0 mg/kg) of the dopamine D2-receptor blocker, pimozide, were administered to rats maintained on an ad lib feeding schedule. Results indicated that 0.25 mg/kg pimozide did not disrupt running activity when compared to control animals. In Experiment 2, injections of either 0, 0.25, or 0.50 mg/kg pimozide were given every 12 hours to rats subjected to the activity stress paradigm. Although 0.25 mg/kg pimozide had no effect on dark-phase activity, it significantly suppressed light-phase activity and subsequently increased the number of survivors in the paradigm. It was concluded that dopamine plays a role in maintaining high running levels in the activity-stress paradigm. PMID- 1523258 TI - Dietary restraint and responsiveness to sensory-based food cues as measured by cephalic phase salivation and sensory specific satiety. AB - Responsiveness to sensory-based food cues was examined in restrained and unrestrained, normal-weight subjects identified with the Three-Factor Eating Questionnaire. Salivary flow rate was measured with no food present and while subjects viewed hot pizza. In the presence of food, restrained eaters had a mean salivary flow rate (0.388 g/min) greater than twice that of the unrestrained eaters (0.186 g/min). During sensory specific satiety testing, subjects tasted and rated the pleasantness of 9 foods, then received a meal of either cheese and crackers or cookies. Changes in pleasantness for the tasted foods were evaluated at 2, 20, and 40 min following the meal. Both restrained and unrestrained subjects displayed similar patterns of sensory specific satiety, i.e., the pleasantness foods which were eaten decreased relative to foods tasted but not eaten. These patterns were unaffected by the type of food consumed in the test meal. These data demonstrate that restrained eaters show moderately enhanced salivary responses but no changes in sensory-specific satiety to food stimuli, suggesting that heightened responsiveness to the sensory properties of foods may not be a generalized phenomenon in restrained eaters. PMID- 1523259 TI - Effect of glucoprivation on self-stimulation rate-frequency functions. AB - In a series of two experiments using rats, the effect of glucoprivation, induced by 2-deoxy-D-glucose (2-DG) or insulin injections, on self-stimulation rate frequency functions, was evaluated at two levels of current intensity. At the higher current intensity, neither insulin nor 2-DG produced a significant change in rate-frequency function parameters. At the lower current intensity, insulin suppressed asymptotic responding while 2-DG produced a lateral curve shift. Results of this study would argue that glucoprivation produces changes in self stimulation at lateral hypothalamic electrodes that are: a) unrelated to the involvement of the neurons in stimulation-induced eating, b) are most notable when a smaller number of reward relevant neurons is stimulated, and c) can be differentially attributed to changes in motoric performance capacity during insulin tests and to changes in the reward value of stimulating current during 2 DG tests. PMID- 1523260 TI - Problem-solving behaviour in apomorphine-susceptible and unsusceptible rats. AB - Pharmacogenetically selected apomorphine-susceptible (APO-SUS) and apomorphine unsusceptible (APO-UNSUS) rats were trained in a discrimination learning paradigm. After the initial discrimination task was solved, reinforcement contingencies were reversed. No differences between APO-SUS and APO-UNSUS animals were found in the rate of learning. However, negative transfer from the initial discrimination to its reversal was less for the APO-SUS rats than for the APO UNSUS rats. Moreover, the APO-SUS rats responded more to the relevant dimension (light) than the APO-UNSUS rats in the last 100 trials before solving the initial problem as well as the reversal. During overtraining on the first problem, APO SUS animals responded less to an irrelevant dimension (position of the lever) than APO-UNSUS animals. In the first 100 trials of the reversal APO-SUS rats responded more to another irrelevant dimension (noise) than APO-UNSUS rats. The data show that APO-SUS and APO-UNSUS rats used the various dimensions (visual, auditory, and spatial) differently in the chosen discrimination learning paradigm. It is concluded that the interline differences found are the consequences of the interline differences in the dopaminergic activity of the ventral and dorsal striatum. PMID- 1523261 TI - Changes in male copulatory behavior after sexual exciting stimuli: effects of medial amygdala lesions. AB - A paradigm was developed to investigate how precoital sexual arousal affects parameters of sexual behavior in male rats. Estrous females in a wire mesh cage were used to induce sexual arousal before the sexual interaction test. In control procedures, males were presented in a wire mesh cage or else there was no stimuli at all. The results indicate that ejaculation latency is consistently reduced after preexposure to a female, but not after preexposure to a male, showing that the effect is specific for precoital sexual arousal. Other parameters were affected by precoital sexual arousal in some, but not in all experiments. Reductions in intromission latency moreover, were observed after both preexposure to a male and preexposure to a female, indicating that general social excitement affects this parameter. Preexposure to females for 10 minutes or 3 hours produced similar results. It was subsequently found that medial amygdala-lesioned (AME) animals differed from sham-lesioned (SHAM) controls with respect to their reaction to precoital sexual arousal. The results show that AME-lesioned animals, in contrast to SHAM-animals, do not show reduced ejaculation latencies after preexposure to an estrous female. The results are in line with the idea that AME lesioned animals are deficient in the assimilation of information on sexual exciting stimuli. PMID- 1523262 TI - Role of the cerebellum in habituation exploration behavior in the rat. AB - Adult control and cerebellectomized DA/HAN-strained male rats were submitted to habituation of exploration behavior in a test environment consisting of a novel cage in which four objects were displayed. Seven days after the initial session of habituation, retention of the habituation was tested. Within-session habituation was observed in cerebellectomized and control rats. However, retention of habituation was impaired in rats that were cerebellectomized after the initial session but not in those cerebellectomized before the session. These results are consistent with the hypothesis that the cerebellum has a role in memory of habituation to environmental stimuli. PMID- 1523263 TI - Repeated weight fluctuation increases plasma insulin in the obese Wistar fatty diabetic rat. AB - Weight fluctuation may contribute to the expression of hyperglycemia in genetically susceptible individuals. Alternating between diets with low and high fat content also may play a contributory role. To test these hypotheses, plasma glucose and insulin levels were measured in obese prediabetic Wistar-Fatty rats after two episodes of diet switching, with and without concomitant weight loss. Following two cycles of weight loss and regain, glucose levels did not differ between weight-cycled rats and static weight controls. However, insulin concentrations of weight-cycled rats were 74% higher than those of controls, suggesting an impairment of insulin resistance. Insulin and glucose levels of animals subjected to episodes of diet switching without accompanying weight loss and regain did not differ reliably from those of controls. A single cycle of weight loss followed by regain appeared to have no effect on either glucose tolerance or insulin resistance. Together, these results suggest that insulin resistance of Wistar-Fatty rats was worsened by repeated weight fluctuation. Further, the effect of repeated weight fluctuation on insulin concentrations is not due to diet switching. Repeated weight fluctuation did not lead to the expression of hyperglycemia under the present conditions. Additional studies are needed to determine what factors modify the effects of weight fluctuation on health, behavior, and metabolism. PMID- 1523264 TI - The role of prostaglandins in interleukin-1 induced gastroparesis. AB - Interleukin-1 is a small molecular weight peptide that is thought to mediate much of the acute phase response to infection, including fever and anorexia and gastric stasis. In the present study, we examined the effects of recombinant human IL-1 alpha (rhIL-1a) on food intake and gastric emptying, and the role of prostaglandins (PG) in IL-1 induced gastroparesis. We report that pretreatment with ibuprofen significantly improved food intake and gastric emptying in IL-1 injected rats, but did not return them to control levels. We conclude that PGs mediate, at least in part, IL-1 induced gastroparesis. The role of gastroparesis in IL-1 induced anorexia remains to be determined. PMID- 1523265 TI - No persistent effect of preweaning nutrition on postweaning food intake, feeding efficiency, or body energy stores in Long-Evans rats. AB - The purpose of this study was to determine the relative importance of pre- and postweaning nutrition on body mass, body fat, and feeding efficiency in Long Evans rats up to a period of 18 weeks following weaning. Female rats were bred and pups were redistributed to form large (14-19 pups), normal (11-13 pups) and small (4 pups) litter groups. Weaned rats were housed as pairs (40 pairs) or singletons (n = 16) and fed either a mixed-fat diet (36.6% fat) or a standard chow diet (13.5% fat). Food intake, body mass, and feeding efficiency were measured at 4, 8, 12, and 18 weeks postweaning. Total body fat and depot fat pad mass were also measured at 18 weeks postweaning. At weaning, pups from small litters were fatter (p less than 0.001), and had a greater mass (p less than 0.03) than pups from large litters. There were no persistent effects of preweaning litter size after covarying for preweaning mass on body mass, and postweaning growth, food intake, feeding efficiency, or body fat accretion. Male rats ingesting the mixed-fat diet had a greater body mass (p less than 0.05), greater body fat accretion (p less than 0.008) and a higher feeding efficiency (p less than 0.001) than their chow-fed counterparts, despite an overall lower energy intake (p less than 0.05). Female rats ingesting the mixed-fat diet had a lower food energy intake (p less than 0.005) and a greater feeding efficiency (p less than 0.001) than chow-fed rats during the early postweaning period, only. Thus, postweaning nutrition may play a more important role in postweaning adult mass and depot fat in freely eating rats than early nutritional experiences. PMID- 1523266 TI - The effects of cocaine on maternal behaviors in the rat. AB - Although recent research has focused on the behavioral teratology of cocaine, there has been little attention centered on the effects of cocaine use on parenting behaviors after birth. This experiment investigated the effects of cocaine on parental (generally termed maternal) behavior in the rat. Four types of adult rats were tested for these effects over a 10-day testing period: lactating primiparous female dams, primiparous females, nulliparous females, and males. Subjects were injected daily with cocaine (5 mg/kg) or saline. Ten minutes postinjection each subject was placed in a cage with three stimulus pups and nesting material, and observed for several measures of maternal behavior for 5 minutes, including sniffing, licking, and retrieving pups. Subjects were also rated on a maternal behavior scale at 60 minutes and 24 hours postinjection, and on nest quality. Cocaine reduced both the total number and duration of sniffing and licking maternal behaviors, and resulted in a lower maternal behavior rating at 60 minutes compared to saline-treated subjects. Among those subjects that retrieved pups within the first 5 minutes, cocaine-injected subjects retrieved for a longer duration. These results also suggest impaired maternal behavior, since rapid retrievals would have been more efficient in maintaining a nest huddle. Thus, cocaine impaired the parenting ability of both male and female rats, with and without previous parenting experience. PMID- 1523267 TI - Abnormal taste preference for saccharin in hypothyroid rats. AB - Taste preferences for saccharin in concentrations ranging from 0.16 mM to 50 mM were determined in rats made hypothyroid with radioactive iodine and in their littermate controls. Hypothyroid rats demonstrated taste preferences for saccharin which were similar to those of controls only at very low (0.016 mM) or very high (49.0 mM) saccharin concentrations. At these concentrations of tastant, the preferences for tastant and water were similar to one another. At a concentration of 5.1 mM, preferences were also very similar in both groups but were very high. At intermediate saccharin concentrations of 1.1 and 3.0 mM, hypothyroid animals showed significantly lower percent preferences for the sweet tastant than did controls, mean +/- SEM (62.48 +/- 5.97 vs. 82.92 +/- 4.60, p = 0.0002) for the 1.1 mM concentration and (74.98 +/- 5.12 vs. 89.40 +/- 2.54, p = 0.0029) for the 3.0 mM concentration. These changes in taste preference for saccharin in hypothyroid rats were similar in direction and magnitude to those previously published by this laboratory using sucrose as the tastant. Thus, hypothyroid rats demonstrate abnormalities in taste preference for both the nonnutritive sweetener, sodium saccharin, as well as for the nutritive sweetener, sucrose. PMID- 1523268 TI - PNMT inhibition decreases exercise performance in the rat. AB - The purpose of this investigation was to examine the effect of phenylethanolamine N-methyltransferase (PNMT) inhibition on the regulation of peripheral metabolic and hormonal responses during treadmill exercise in the rat. Changes in plasma catecholamine (epinephrine, norepinephrine, and dopamine), glucagon and glucose, and the glycogen content of the liver and two skeletal muscles were studied in four groups of rats. Two groups of rats were studied at rest: one group had been treated with LY134046, an inhibitor of PNMT, and the second group was treated with physiological saline. A third group treated with LY134046 was studied after treadmill exercise (28 m.min-1 and 8% slope). In this group of rats, exhaustion came after 37.5 +/- 7.9 minutes of exercise. In order to make appropriate comparisons, a fourth group of rats treated with physiological saline was exercised for 37.5 min. Running endurance during the treadmill exercise was thus reduced in LY134046-treated rats. Plasma epinephrine and glucagon concentrations and other metabolic (plasma glucose and gastrocnemius lateralis and superficial vastus lateralis muscles and liver glycogen contents) responses were similar between LY134046- and saline-treated rats at rest and after exercise. These results suggest that PNMT inhibition in epinephrine brain neurons might be the principal factor involved in the LY134046-induced reduction of exercise endurance. PMID- 1523269 TI - Relationships between epinephrine, waking time, and self-estimates for naps at night. AB - In a previous study, we established a basal regression line between epinephrine excretion and percent of waking time in bed-rested humans under conditions involving minimal stress. We suggested that this regression line might be clinically useful for observing insomnia. The present study was undertaken to examine whether epinephrine excretion during short-duration sleep, such as naps, is influenced by a transient insomniac state. Polysomnograms during a 2-hour nap from 0000 to 0200 were recorded three times for six healthy male subjects. Epinephrine excretion levels during sleep were found to increase along the basal regression line when percent of waking time went up. The subjects with over 30% waking time during this 2-hour period reported that their sleep was light and not satisfactory at all. These results support our position that the regression line can be useful for observing a transient insomniac state. PMID- 1523270 TI - Auditory potentials elicited by the grass photic stimulator in the rat. AB - Flash visual evoked potentials were recorded from the rat to determine whether the Grass photic stimulator could generate an auditory component of the waveform. When the click associated with each lamp flash remained unmuffled, the primary response of the visual cortex (P30) was preceded by an earlier positivity with a latency between 6-8 ms. When the photic stimulator lamp was subsequently insulated in order to deaden the sound of the click, the P30 potential remained intact while the earlier response disappeared. It is concluded that the photic stimulator is capable of eliciting a distinct auditory potential of probable collicular origin. PMID- 1523271 TI - [Preparation of Fifty-items Neurotic Index (FNI), a new questionnaire for neurotic patients]. PMID- 1523272 TI - [Mechanism of attention in sleep--the changes of waveforms of event-related potentials in sleep]. AB - Since attention has such a close correlation with arousal level, the influence of sleep on the waveforms of event related potential (= ERP) must be studied in advance for evaluating attentiveness of human mental activity. ERP, which odd ball paradigm was used to elicit, was examined in 9 adult and healthy subjects from arousal to sleep. And ERP during a whole night was also examined in 5 of them to study the relation of the waveforms of ERP and sleep stages including a stage of rapid eye movement. As a result, there were some clear differences between the waveforms of the rare and frequent stimuli, and with change of sleep stages the differences also changed. Remarkable increase of amplitude and prolongation of latency of P200 and N200 were found in the waves of target stimuli in stage I. Activities of both components were connected with each other like a complexed component and preceded by the change of P300 activities. The waveforms of target stimuli in stage II had same kind of components with those of arousal stage. There were increased P200, N200, P300 activities and subsequent large negative activity which we called N3. These components were not clear in the waveforms of non-target stimuli. But P300 and N3 components were disappeared gradually during stage III. The averaged waveforms in stage III accompanied with 14-16 Hz fast wave suggested that they were identical with K-complex of sleep EEG. Add to this result, the habituation usually observed on P200 and N200 of nontarget stimuli in arousal let us to think that they are also identical with orienting reflex by rare and novel stimuli of external events (Sokolov). According to the result of examination changing the probability of target stimuli (20%----50%----80%), the waves of target stimuli in stage II were dependent on the probability of rare stimuli as well as in arousal stage. The dependence on probability was thought to reflect an automatic processing of selecting stimuli by orienting reflex in sleep. Another 3 subjects were examined of auditory evoked response in sleep with the same stimuli and without a task of counting numbers of rare stimuli. In stage II, however, they showed the waveforms by rare stimuli just like those by rare and target stimuli of 9 subjects. Then, it was supposed that attentiveness for external stimuli might be existent in sleep and changeable with sleep stages. PMID- 1523273 TI - [Influence of family history over several generations on schizophrenic patients- study of a special type of stem family where a husband is found for the heiress]. AB - Family histories over several generations were studied, since it was considered that these might have various influences on the descendants, We hypothesized that poor home management policy by the parental generation would have greater influence on the onset of schizophrenia in the offsprings, and later their social adjustment. To test this theory, twenty families of a special type, called "mukotori-kazoku" in Japanese, which literally means a family that takes in a husband for the sole heiress in the absence of a male heir, were chosen; ten of these families had a schizophrenic patient (schizophrenic group) and the other ten did not (control group). In this type of stem family, the husband (bridegroom) changes his family name to that of the wife and lives with the wife's family, to whom he is generally obliged to devote himself. Such a "mukotori-kazoku" tends to be run mainly in order to preserve or develop the family, and thus provides a good model for investigation of home management policy. Before presenting the results of this study, our former findings should be mentioned. We found that there tends to be a cycle in the family history over several generations consisting of three periods: a period of destruction, a period of reconstruction and a period of stability. All of the schizophrenic patients we studied previously became ill as the cycle was approaching the period of stability. The results of the present study were as follows. In the schizophrenic group on the maternal side, there was always a period of destruction during the great-grandparents' and/or grandparents' generation. Most of the patients' mothers (heiresses) were forced to devote themselves to family reconstruction and had married unwillingly. Similarly, in the former generation on the paternal side, a period of destruction was often observed. Most of the patients' fathers had been treated as a nuisance in their family or origin, and had been obliged to marry out of the family, and/or they had considered that marriage was the easiest path to economic independence. The patients' family members were so indifferent to the father that he became isolated within the family.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1523274 TI - [Studies of the correlations between morphological brain changes on MRI and computerized EEG changes in schizophrenics]. AB - Several researchers have investigated the relationships between computed tomographic and electroencephalographic abnormalities in schizophrenics. In this present investigation, 28 medicated schizophrenic patients fulfilling the DSM-III R criteria for schizophrenia and 21 normal volunteers were studied by means of MRI and EEG examinations. All subjects had given informed consent to the investigation. The schizophrenic patients (14 males, 14 females) were aged from 21 to 39 with a mean age of 30.2. The control group consisted of age- and sex matched healthy volunteers (11 males, 11 females) with no history of neurological disease or head trauma. All the subjects were right-handed as determined by the Edinburgh Inventory. Schizophrenic and control subjects underwent MRI scan and EEG within two weeks. Three trained psychiatrists evaluated patients for BPRS and SANS and the score each item was the median of the three raters. MRI scans were performed by a Asahi Super 200 scanner operating at a 2.0 Tesla magnetic field. A midsagittal scan (8 mm thickness, Spin Echo 500/26) was taken. Subsequently, 15 axial and coronal slices of 5 mm interslice with 2 mm gap were obtained using an Inversion-Recovery sequence (TR: 3000, TI: 800, TE: 14). For measurement purposes, the three MRI scans (Fig-1) were recorded on transparent film, and the boundaries of the cerebral structures were taken traced from the film onto a digitizing tablet. The EEGs were recorded from 16 scalp electrodes of the standard 10/20 system referenced to linked ear electrodes at rest and digitized by a topographic system (Neuromap system MCE-5100, QCE-510B, Nihon Kohden). To calculate EEG power, the frequency spectrum was divided into six EEG frequency bands by 0.25 Hz bands. Each power value was taken from the average percentage of total power and then log-transformed. Schizophrenic patients showed a significantly larger VBR on the axial and coronal planes than control subjects. The areas of the bilateral anterior horns, left body, left posterior horn of the lateral ventricle and the third ventricle were significantly larger in schizophrenic patients than in control subjects. The area of middle half of the corpus callosum in schizophrenic patients was smaller than in control subjects. Schizophrenic patients showed more delta and theta activities in the centro parieto-occipital regions than control subjects. Schizophrenic patients also showed more beta 1 and beta 2 activities in front-central regions than control subjects. On the other hand, schizophrenic patients showed a markedly decrease in alpha 2 activity in all regions.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1523275 TI - Advice and information from a former editor. PMID- 1523276 TI - Rebound insomnia and newer hypnotics. AB - The prescription of hypnotics, mostly benzodiazepines, continues at a high level. One problem with their use is rebound insomnia: upon discontinuation sleep worsens compared with pretreatment levels. Factors influencing rebound include the type of subject, the duration of action of the hypnotic, the dosage and perhaps duration of treatment. The detection of rebound requires both sleep laboratory and clinical studies with night-by-night analyses of individual patient data. This review concentrates on the newer compounds, (quazepam and zolpidem) which act selectively on subtypes of benzodiazepine receptors or bind atypically (zopiclone). It concludes that present evidence, while limited, is consistent with claims of less rebound potential than older benzodiazepine hypnotics of equivalent duration of action. Nevertheless, further rigorous studies are essential before these claims can be totally accepted. PMID- 1523278 TI - Effects of repeated MK-801 on ambulation in mice and in sensitization following methamphetamine. AB - The noncompetitive NMDA receptor antagonist MK-801, (+)-5-methyl-10,11-dihydro-5H dibenzo-[a,d]-cyclohepten-5,10-imine , increased ambulatory activity in the mouse at doses over 0.1 mg/kg (IP). The effect was enhanced when 0.3 mg/kg MK-801 was repeatedly administered at intervals of 3-4 days. In contrast, a reduction of the effect was induced with repeated doses of 0.1 and 1 mg/kg. The mice that had repeatedly experienced 1 mg/kg MK-801 exhibited a decrease in the sensitivity to methamphetamine (2 mg/kg SC). In addition, the repeated co-administration of 1 mg/kg MK-801 with methamphetamine induced a decrease in the sensitivity to methamphetamine. No modification of methamphetamine sensitivity was elicited by 0.1 and 0.3 mg/kg MK-801 in both the single and co-administration schedules. On the other hand, established sensitization to methamphetamine was hardly affected by repeated treatment with 0.1-1 mg/kg MK-801. These results indicate that the mechanism of the inhibitory action of MK-801 on the development of methamphetamine sensitization is different from that of dopamine D2 antagonists, which may act to decrease the effective unit dose of methamphetamine and reduce ambulation-increasing effect of methamphetamine. PMID- 1523277 TI - Effects of ritanserin and chlordiazepoxide on sleep-wakefulness alterations in rats following chronic cocaine treatment. AB - The effects of ritanserin, a 5-hydroxytryptamine-2 (5-HT2) receptor antagonist, and chlordiazepoxide, a benzodiazepine agonist, on sleep-wakefulness disturbances in rats after acute administration of cocaine and after discontinuation of chronic cocaine treatment were examined. Intraperitoneal (IP) injection of chlordiazepoxide (10 mg/kg) but not ritanserin (0.63 mg/kg) prevented the increase of wakefulness (W) and the reduction of light slow wave sleep (SWS1) and deep slow wave sleep (SWS2) induced by an acute injection of cocaine (20 mg/kg IP). Daily injection of cocaine (20 mg/kg for 5 days, then 30 mg/kg for 5 days IP) at the onset of the light phase elicited an increase of W and a concomitant decrease of SWS1, SWS2 and paradoxical sleep (PS) in the light phase, followed by a rebound in SWS2 and PS in the subsequent dark phase. Following cocaine discontinuation, the circadian distribution of sleep-wakefulness states remained disturbed in saline-treated rats for at least 5 days. Both ritanserin (0.63 mg/kg IP/day) and chlordiazepoxide (10 mg/kg IP/day) reduced the alteration in the distribution of W and SWS2 throughout the light-dark cycle from the first day of administration on, but failed to prevent PS alterations. The mechanisms by which both compounds exert their effect are probably quite different. For chlordiazepoxide sedative and sleep-inducing properties probably play a major role. In contrast, for ritanserin SWS2-increasing properties and its ability to reverse preference for drugs of abuse without inducing aversion might be key factors. PMID- 1523279 TI - Social status and voluntary alcohol consumption in mice: interaction with stress. AB - Dominant rats are found to consume less alcohol than their subordinate cage mates. It is unclear whether the difference is due to dominant, aggressive animals consuming low levels of alcohol or whether social stress increases alcohol intake in subordinate animals. The present study investigated alcohol drinking patterns in aggressive alpha mice, their fight-stressed submissive cage mates and non-fighting control mice before and after the establishment of social hierarchies. The results revealed that both moderately and severely fight stressed submissive mice showed increased consumption of 5% alcohol, expressed as g/kg, but only severely wounded submissive mice showed increased alcohol preference over total fluid consumption, as compared with alpha mice. The difference in alcohol consumption was not seen prior to the establishment of submissive and alpha status, indicating that the submissive mice increased their alcohol consumption only after experiencing fight-stress. The amount of alcohol consumed did not differ between alpha and non-fighting control mice. To further investigate the possible connection between alcohol intake and aggressivity, the mice were studied in the resident-intruder test before group-housing. The results failed to show a consistent pattern of correlations between the time spent in aggression in this test and subsequent alcohol intake measures. The data indicate that severe fight-stress increases alcohol consumption in mice. Alcohol intake of aggressive, dominant alpha mice is not significantly altered, as compared with non-fighting animals. Furthermore, the level of aggressiveness prior to the establishment of social status does not directly affect alcohol consumption.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1523280 TI - Effects of increasing response requirement on choice between cocaine and food in rhesus monkeys. AB - Rhesus monkeys were trained in a discrete-trials choice procedure and allowed to choose between intravenous injections of cocaine (0.01-1.0 mg/kg/injection) and food presentation (1 or 4 pellets; 1 g/pellet) during daily 7-h experimental sessions. When each reinforcer was available under a fixed-ratio (FR) 30 schedule, the frequency of cocaine choice and the total drug intake increased in a dose-related manner for all monkeys. When the FR for cocaine was differentially increased, the frequency of cocaine choice decreased, shifting the cocaine dose response function to the right and/or downward. When the FR for cocaine was at least 480, cocaine preference could not be recovered up to doses of 1.0 mg/kg/injection. In a second experiment, when the response requirement for food was differentially increased, the frequency of cocaine choice increased. These results demonstrate that altering the response requirement for cocaine or for alternative reinforcers that are available can substantially affect cocaine self administration. PMID- 1523281 TI - Oral self-administration of triazolam, diazepam and ethanol in the baboon: drug reinforcement and benzodiazepine physical dependence. AB - Reinforcing and physical dependence-producing effects of oral diazepam and triazolam (0.01-1.28 mg/ml) were studied in four non-water-deprived baboons in daily 2-3-h sessions. Drinking initially was food-induced, but subsequently it was maintained for greater than year without the inducing procedures; drug intake greater than 10 mg/kg per session was attained. Triazolam and diazepam reinforcement (compared to vehicle) was concluded for only one baboon for each drug under a single-spout procedure and for two baboons for each drug under a two spout procedure. However, all baboons showed ethanol reinforcement under a two spout procedure. When a lever-pressing requirement was imposed for each drink (one-spout procedure), ethanol maintained requirements of 128 or 256 responses/drink, and volume of ethanol consumed was greater than vehicle. Neither benzodiazepine maintained lever pressing better than vehicle at any response requirement and drinking was suppressed by requirements of 1-32. Physical dependence to triazolam and diazepam developed after approximately 1 month of daily ingestion, evidenced by a precipitated withdrawal syndrome after injection of the benzodiazepine antagonist flumazenil. A mild spontaneous withdrawal syndrome occurred after substitution of vehicle for triazolam or diazepam. These data indicate a clear dissociation between the reinforcing and physical dependence-producing effects of triazolam and diazepam. PMID- 1523282 TI - Amitriptyline, clovoxamine and cognitive function: a placebo-controlled comparison in depressed outpatients. AB - No longer prescribed only for vegetative signs of depression, tricyclic antidepressants also lessen depressive cognitive distortions. Less clear is whether they ameliorate depressed patients' other cognitive deficits in memory, information processing speed, and psychomotor performance. We tested the alternative hypothesis that amitriptyline, because of its anticholinergic and sedative properties, would exacerbate depressed patients' cognitive disturbances. Depressed outpatients received double-blind placebo (n = 15), amitriptyline (n = 10), or clovoxamine fumarate (n = 10), a serotonin reuptake inhibitor relatively lacking in anticholinergic properties. Depression, memory, and psychomotor performance were assessed at baseline and after 7 and 28 days of drug treatment. Depression was alleviated after all treatments, including placebo. Only amitriptyline impaired performance on tests of memory, producing a significant decrement, relative to placebo, after 4 weeks of treatment. None of the treatments adversely affected performance on psychomotor tasks. These findings add to the evidence that antidepressant drugs with high anticholinergic activity can impair memory, despite alleviation of depression. PMID- 1523283 TI - Are there changes in sensitivity to 5-HT3 receptor ligands following chronic diazepam treatment? AB - Administration of 1-(3-chlorophenyl)-biguanide (mCPB), a 5-HT3 receptor agonist (1 and 10 mg/kg IP), was found to be significantly anxiogenic in vehicle treated rats tested in the plus-maze, while having no significant effect in rats withdrawn for 24 h from 21 days diazepam treatment (2 mg/kg/day), suggesting a decreased agonist action at 5-HT3 receptors following withdrawal from chronic diazepam treatment. In the social interaction test, diazepam withdrawn rats showed a significant decrease in social interaction when compared to the chronic vehicle treated group. This anxiogenic response was reversed by low doses of zacopride (0.0001-0.01 mg/kg IP); in the vehicle treated animals 0.1 mg/kg was significantly anxiogenic. The overall pattern of results with zacopride is explained by suggesting that the anxiogenic effects of high doses of zacopride are detectable at low levels of 5-HT function and are due to an agonist action of the S-isomer in the rat at 5-HT3 receptors. The anxiolytic action of low doses is attributed to the R-isomer acting at the R-zacopride binding site and is enhanced in conditions of high 5-HT function, e.g. in the diazepam withdrawn rats. If this hypothesis is correct, then we would predict the R-isomer alone would be more effective in reversing the anxiogenic effects of diazepam withdrawal than the racemate, used here. PMID- 1523284 TI - Effects of chlorpromazine and lorazepam on explicit memory, repetition priming and cognitive skill learning in healthy volunteers. AB - To assess the influence of neuroleptics on explicit memory and two forms of implicit memory, repetition priming and cognitive skill learning, the effects of two low doses of chlorpromazine (12.5 and 25 mg orally) were contrasted to those of lorazepam (2.5 mg orally) and of a placebo using a free-recall task, a word completion task and repeated testing on the Tower of Toronto puzzle, a version of the Tower of Hanoi puzzle. Seventy-two healthy volunteers took part in this double-blind study. Chlorpromazine spared free-recall and word-completion performance, but impaired the acquisition of a cognitive routine in the subjects who completed the first trials of the Tower of Toronto puzzle efficiently. Lorazepam induced an opposite pattern of memory disruption. These preliminary results suggest that chlorpromazine and lorazepam induced a double dissociation between priming and the acquisition of a cognitive routine. They provide evidence that the two forms of implicit memory rely upon distinct neurochemical systems, the latter, but not the former, being dependent upon dopaminergic systems. PMID- 1523285 TI - MK-801 produces a reduction in anxiety-related antipredator defensiveness in male and female rats and a gender-dependent increase in locomotor behavior. AB - The present study investigated the effects of the non-competitive NMDA antagonist MK-801 (0.04-0.16 mg/kg), on antipredator defensive reactions of male and female rats in three paradigms comprising the Anxiety/Defense Test Battery (A/DTB). In order to facilitate interpretation of data from the above study, the behavioral effects of the compound were also assessed in the non-threatening environment of the home cage. The data indicate a marked gender difference in the locomotor effects of the compound with females, but not males, showing a dose-dependent increase in general locomotor activity, a decrease in freezing, and a loss of balance at the highest dose, in both non-threatening and threatening contexts. The behavioral profile for males in the A/DTB included decreased orientation to and proxemic avoidance of the cat stimulus or stimulus site, and increased transits and eating in the cat situation. Contacts with the cat odor stimulus were increased, as was normal, curved back, locomotion in this test. In the absence of non-specific locomotor effects for males, this profile for the A/DTB provides convincing evidence for anxiety/fear reduction with MK-801. While locomotor effects tended to mask the putative anxiolytic properties of the compound in females, evidence remains from behavioral changes not attributable to a locomotor influence to indicate anxiety/fear reduction in this sex. PMID- 1523286 TI - Differential effects of diazepam and lorazepam on repetition priming in healthy volunteers. AB - The effects of two benzodiazepines, diazepam (15 or 20 mg orally) and lorazepam (1.75 or 2.5 mg orally), and a placebo on explicit memory, lexical priming and perceptual priming were assessed using a free-recall, a word-completion and a picture-completion test. The picture-completion test included two different study conditions intended to manipulate the magnitude of the priming effect. Sixty healthy volunteers took part in this double-blind study. Free-recall performances were altered by both drugs. Lorazepam impaired word-completion and picture completion performance, whereas diazepam only exhibited a deleterious effect on the more sensitive of the two measures of the picture-completion test. These results indicate that the two benzodiazepines have differential amnestic effects. It is suggested that these differential effects could be accounted for by a different cortical distribution of the two benzodiazepines. PMID- 1523287 TI - Effect of the 5-HT1A partial agonist buspirone on regional cerebral blood flow in man. AB - Repeated measurements of regional cerebral blood flow (rCBF) were made in normal volunteers before, and after, the administration of the 5-HT1A partial agonist, buspirone, or placebo. The difference in rCBF, before and after drug, (buspirone versus placebo) was used to identify brain areas affected by buspirone. Buspirone induced changes in rCBF were studied under two behavioural conditions (5 word list learning and 15 word-list learning). Compared to placebo, buspirone increased blood flow in the cuneus during both behavioural states. However, decreases in blood flow, centred in the left dorso-lateral prefrontal cortex and posterior cingulate cortex, were only observed under one of the two behavioural conditions. It is concluded that buspirone-induced alterations in regional cerebral blood flow are better understood, not in relation to the known distribution of monoamine neurotransmitter systems (particularly ascending 5-HT projections), but rather in relation to putative neuronal circuits possibly many synapses "downstream" of buspirone's pharmacological site of action. PMID- 1523289 TI - Focal manifestations of diffuse liver disease at MR imaging. AB - Detection and exclusion of focal liver lesions is especially difficult in patients with diffuse liver disease. Magnetic resonance (MR) imaging may be particularly valuable in these patients. By judicious comparison of appropriate pulse sequences, normal and hypertrophic liver may be distinguished from atrophic, neoplastic, or otherwise abnormal hepatic parenchyma. Chemical shift (lipid-sensitive) techniques allow definitive identification of fatty liver, including focal fatty infiltration or focal sparing. T2-weighted and T2*-weighted images allow identification of iron overload, depicting malignancies as focal masses without iron. Analysis of signal intensity and internal morphology allows confident distinction between regenerative nodules and hepatocellular carcinoma in most instances, and allows diagnosis of early carcinoma within regenerative nodules. MR imaging provides capabilities for noninvasive characterization of liver tissue beyond those available with other noninvasive modalities. PMID- 1523288 TI - Slow wave sleep and 5-HT2 receptor sensitivity in generalised anxiety disorder: a pilot study with ritanserin. AB - Eight patients with generalised anxiety disorder (GAD) and eight matched healthy controls had their polysomnogram measured on two occasions separated by 1 week. On one occasion they received the 5-HT2 receptor antagonist, ritanserin (5 mg orally) and on the other matching placebo. The increase in slow wave sleep produced by ritanserin was the same in GAD patients as in healthy controls. These findings do not support the hypothesis that GAD is associated with a generalised hypersensitivity of brain 5-HT2 receptors; however, the present data cannot exclude the presence of a regionally specific change in this receptor subtype in anxiety disorders. PMID- 1523290 TI - Lateral arcuate ligaments of the diaphragm: anatomic variations at abdominal CT. AB - The authors have occasionally observed nodular areas abutting the lateral diaphragmatic surface and extending into the posterior pararenal space on computed tomographic (CT) scans. Review of the anatomy literature revealed that this finding represents inferolateral extension of the lateral arcuate ligaments, which reflect over the quadratus lumborum muscles to fuse with the diaphragm. CT scans from 100 consecutive patients were reviewed to determine the frequency, relationship to habitus, and appearance of this finding. Nodularity was found in five patients (bilateral in three, unilateral in two). The average size was 9.4 mm in the transverse plane, 6.3 mm in the anteroposterior plane, and 4.3 cm in the cephalocaudal plane. The extent of retroperitoneal fat was normal in all five patients. In one patient, there were easily visible lobulations; three patients had prominent lobulations, and one patient had few lobulations. It is important to recognize this anatomic variant to avoid confusion with disease. PMID- 1523291 TI - Prenatally detected myelomeningoceles: sonographic accuracy in estimation of the spinal level. AB - The sonograms and case records of 53 patients with prenatally detected myelomeningoceles were retrospectively reviewed. Sonographic findings were correlated with pathologic, surgical, and/or radiographic findings in 28 cases. Fourteen mothers chose to continue their pregnancies, and the level of neuromotor deficit was available for 11 children of this group. The sonographic and pathologic levels were in agreement in 18 of 28 cases (64%) and were within one spinal level in 22 of 28 cases (79%). The pathologic level of the lesion was underestimated (sonographic level lower than pathologic) in three fetuses and overestimated (sonographic level higher than pathologic) in another three. In 10 of 11 living children (91%) the neuromotor level was equal to or better than the anatomic level. The authors conclude that ultrasonography can, in most cases, allow accurate prediction of the level of the spina bifida lesion and the severity of neuromotor handicap in children with prenatal diagnoses of myelomeningocele. PMID- 1523292 TI - Distention of the posterior urethra: association with nonneurogenic neurogenic bladder (Hinman syndrome). AB - In nonneurogenic neurogenic bladder (NNNB), or Hinman syndrome, a functional bladder outlet obstruction is produced by voluntary contraction of the external sphincter during voiding. To determine whether any radiographic findings are diagnostic of this condition, the authors reviewed the genitourinary images of six boys in whom NNNB was diagnosed in the past 5 years. In contrast to true neurogenic bladder, findings of elongated, trabeculated, high-volume bladders with substantial postvoid residuals, obstructive uropathy, and vesicoureteral reflux were not associated with clinical, radiographic, or urodynamic evidence of an underlying neurologic abnormality. Furthermore, four boys had distention of the posterior urethra that the authors believe is suggestive of this condition. In these patients, the posterior urethra appeared entirely normal during early voiding, but distended after contraction of the external sphincter as voiding progressed. This posterior urethral distention may worsen the symptoms of enuresis, but may also reduce or retard the damage to the proximal urinary tract. PMID- 1523293 TI - Fractures of the rib head in abused infants. AB - Fractures of the posterior ribs are well-recognized sequelae of infant abuse. Previous reports have indicated a predilection for fracture near the costotransverse process. This study expands the spectrum to include fractures involving the rib head. The radiologic and histologic features are described, and the mechanism of injury of this lesion is examined. In situ and specimen radiography, followed by histopathologic examination, was performed in 78 ribs removed from seven abused infants who died with posterior rib fractures. Computed tomography of the intact posterior thorax was performed in two of these infants. Fifty posterior rib fractures were identified; 29 involved the rib head. Frontal radiography was insensitive in identifying these fractures, clearly revealing injury only when periosteal reaction was present (four of 29 cases). Axial specimen radiography delineated the fractures in all cases. In the two infants studied, CT depicted five of 19 fractures visible only with axial specimen radiography. The morphologic features of these fractures further support the concept that most fractures in abused infants occur by means of indirect forces and are consistent with anteroposterior manual thoracic compression during assaults. PMID- 1523294 TI - Thyroid nodules associated with Hashimoto thyroiditis: assessment with US. AB - Sonographic findings in 109 thyroid nodules in 104 patients with Hashimoto thyroiditis were retrospectively analyzed. Sixty patients underwent ultrasound (US)--guided fine-needle aspiration (FNA) biopsy (65 nodules, 24 palpable, 27 surgically confirmed), 14 of whom also underwent palpation-guided FNA (14 nodules, all palpable, all surgically confirmed). Forty-four patients (44 nodules, 25 palpable) underwent diagnostic US followed up with surgery. US-guided FNA helped differentiate between benign (n = 11) and malignant (n = 16) diseases (sensitivity, 100%). Two papillary carcinomas were falsely diagnosed as Hashimoto thyroiditis with palpation-guided FNA. Eight malignancies were not palpable, and correct diagnosis was obtained with US-guided FNA. Hyperechoic nodules were usually benign, and isoechoic nodules had a low frequency (13%) of malignancy. Most carcinomas were found in hypoechoic masses, and almost all lymphomas were found in markedly hypoechoic masses. Lymphoma was indistinguishable from pseudotumor in Hashimoto thyroiditis or adenomatous hyperplasia at US. US-guided FNA is helpful in making the histologic diagnosis in thyroid nodules associated with Hashimoto thyroiditis. US-guided FNA is clinically beneficial because it can help select patients who need surgery, avoiding unnecessary surgery for patients with nonneoplastic disorders. PMID- 1523295 TI - How good (or bad) is film processing? PMID- 1523296 TI - Human eye: visualization of perfluorodecalin with F-19 MR imaging. AB - Perfluorodecalin (PFD) was demonstrated in a human eye with fluorine-19 magnetic resonance (MR) imaging by employing a standard two-dimensional fast low-angle shot (FLASH) sequence. The presence and intraocular distribution of PFD were revealed despite the posterior eye segment being obscured by a narrow pupil, multiple small intraocular gas bubbles, and an intraocular hemorrhage. This examination can be performed with standard sequences on MR imaging systems equipped with a fluorine channel. PMID- 1523297 TI - Lumbar disk herniation: MR imaging assessment of natural history in patients treated without surgery. AB - The aim of this study was to evaluate the evolution of lumbar disk herniation in patients treated without surgery. Sixty-nine patients with a lumbar disk herniation proved at magnetic resonance (MR) imaging underwent a follow-up MR imaging study. The disk herniations evaluated during both MR imaging examinations were measured and classified into four categories according to the change in size that occurred. The patients were also divided into three clinical classes on the basis of the clinical outcome. Sixty-three percent of the patients showed a reduction of disk herniation of more than 30% (48% had a reduction of more than 70%), while only 8% demonstrated worsening of the clinical picture. These findings suggest that lumbar disk herniation may be primarily a medical (nonsurgical) disease and that MR imaging could play an important role in management of and research into the disorder. PMID- 1523298 TI - Neurologic complications of petrosal sinus sampling. AB - Petrosal sinus sampling has been described as an innocuous, essentially risk-free procedure. The authors report on two patients from two different institutions who sustained brain stem injury as a result of petrosal sinus sampling and two other patients in whom brain stem injury was avoided. Major neurologic complications have occurred in only 0.2% of procedures (one of 508) performed at the National Institutes of Health and in 0.5% of a subset of these procedures (one of 184) that were performed with a specially designed petrosal sinus catheter. The cause of these complications is unclear but is presumed to be localized venous hypertension. Tip-deflector catheter-guide-wire systems, if available, are recommended for petrosal sinus sampling. Inadequate data exist to permit recommendation of any other catheter. Brain stem injury is preventable if the catheter is withdrawn at the earliest sign of even a minor, seemingly insignificant problem. Subtle symptoms and signs that may not appear to be neurologic may herald a clinical catastrophe if not heeded. PMID- 1523299 TI - Evaluating the roles and function of vena caval filters: will data be available before or after these devices are removed from the market? PMID- 1523300 TI - Liver metastases from colorectal carcinoma: detection with continuous CT angiography. AB - A diagnostic approach to assess liver metastases from colorectal carcinoma was prospectively evaluated in 30 patients with and without metastases on the basis of findings at conventional computed tomography (CT). With the technique, termed continuous CT angiography (CCTA), CT data were continuously sampled for 24 seconds at the same section level after initiation of a 3-second injection of 10 20 mL of contrast medium in the common hepatic artery. The procedure was repeated for each contiguous section level of the liver. Findings at preoperative ultrasound (US), conventional CT, and CCTA were compared with those at intraoperative US and surgical exploration as the standard of reference. Forty four liver metastases were identified in 16 patients, and 14 patients had no metastases. CCTA had a sensitivity of 98% (43 lesions identified) and higher accuracy (81% [54 of 67 diagnoses]) than US and conventional CT. The data indicate that CCTA can supplement information obtained with conventional imaging techniques in patients who must undergo hepatic surgery because of metastases from colorectal carcinoma. PMID- 1523301 TI - Evaluation of radiation-induced liver injury with MR imaging: comparison of hepatocellular and reticuloendothelial contrast agents. AB - Gadolinium (4s)-4-(4-ethoxybenzyl-3,6,9-tris(carboxylato-methyl)-3,6,9- triazaudecandioic acid (EOB) diethylenetriaminepentaacetic acid (DTPA), a hepatocellular-directed magnetic resonance (MR) contrast agent, and coated superparamagnetic iron oxide particles (SPIO), a Kupffer cell-directed contrast agent, were compared for uptake and enhancement in a rodent model of radiation induced liver injury. A single x-irradiation exposure (50-70 Gy) was delivered to one side of the liver in 18 rats. MR imaging was performed 3 days after x irradiation with sequential injections of the two contrast agents in the same rats. Additionally, biliary excretion of Gd-EOB-DTPA was quantified after whole liver irradiation in five rats. Electron microscopy of the irradiated liver demonstrated mitochondrial injury in both hepatocyte and Kupffer cell populations. With Gd-EOB-DTPA, however, liver enhancement and biliary excretion were not affected by irradiation. Uptake of SPIO was decreased in the irradiated portion of the liver, with a precise demarcation between irradiated and nonirradiated zones at MR imaging. PMID- 1523302 TI - Right-sided segmental infarction of the omentum: clinical, US, and CT findings. AB - Clinical, ultrasound (US), and computed tomographic (CT) findings at hospital admission and follow-up were retrospectively studied in seven patients with right sided segmental infarction of the omentum. In all patients, the presumptive clinical diagnosis was appendicitis, although in three patients cholecystitis and pyelitis were also considered. US revealed an ovoid or cakelike, moderately hyperechoic, noncompressible lesion adherent to the peritoneum and located at the level of the umbilicus, anterolateral to the right half of the colon. On CT scans, a corresponding, better defined area of fat interspersed with hyperattenuating streaks was found. No abnormality of bowel or appendix was seen. The clinical symptoms and abnormalities on US scans gradually disappeared in all patients. Because no patient underwent surgery, no histologic proof was obtained. In all patients, however, the clinical, US, and CT findings were similar and consistent. They corresponded to the abnormality called right-sided segmental omental infarction in the surgery and radiology literature and enabled exclusion of appendicitis, thus preventing unnecessary surgery. PMID- 1523303 TI - Gastric tumors: radiologic-pathologic correlation and accuracy of T staging with dynamic CT. AB - Incremental dynamic computed tomography (CT) was prospectively performed in 89 patients with gastric tumors (78 gastric cancers, five malignant lymphomas, and six submucosal tumors) after the intake of 400 mL of water, and findings were compared with those obtained at pathologic examination. Dynamic CT of healthy control subjects (15 patients without gastric lesions) showed the gastric wall as a two- or three-layered structure (multilayered pattern): a markedly enhanced inner layer; an intermediate layer of low attenuation; and (sometimes) an outer layer of slightly high attenuation, which corresponded histologically to the mucosal layer, submucosal layer, and muscular-serosal layer, respectively. In 68 lesions that were removed at surgery, the detectability of early and advanced gastric cancers and the accuracy of classification of gross appearance and serosal invasion as determined with CT were 53%, 92%, 80%, and 80%, respectively. All detected advanced gastric cancers were seen as enhanced areas with the destruction of the multilayered pattern. Differentiation between infiltrating gastric cancer (n = 5) and malignant lymphoma (n = 5) was successful. Five of six submucosal tumors were demonstrated as having an overlying intact mucosal layer. PMID- 1523304 TI - Immunoscintigraphy performed with In-111-labeled CYT-103 in the management of colorectal cancer: comparison with CT. AB - Immunoscintigraphy performed after intravenous administration of indium-111 labeled CYT-103, an immunoconjugate of monoclonal antibody B72.3, was evaluated in patients with suspected primary or recurrent colorectal cancer at 25 centers in the United States. Gamma camera imaging, computed tomography (CT), and confirmatory surgical exploration were completed in 169 of 227 patients who received single infusions of In-111 CYT-103. Eight patients (3.5%) had reversible, nonserious adverse reactions, and 39% developed antimurine antibodies. Surgery revealed that 155 of 169 patients had colorectal carcinoma. In these 155 patients, immunoscintigraphy and CT demonstrated similar sensitivity (69% and 68%, respectively) and specificity (77%). However, immunoscintigraphy had greater sensitivity in detection of pelvic tumors (74% vs 57%, P = .035) and extrahepatic abdominal tumors (66% vs 34%, P less than .001); CT enabled detection of a greater proportion of liver metastases (84% vs 41%, P less than .001). These results indicate that In-111 CYT-103 can be administered safely and that immunoscintigraphy performed with this agent frequently enables identification of extrahepatic abdominal sites of disease not visualized with CT. PMID- 1523305 TI - Hepatic metastases from colorectal cancer: radiologic strategies for improved selection. PMID- 1523306 TI - Gastrointestinal bleeding: improved localization with cine scintigraphy. AB - Studies of gastrointestinal bleeding, done with technetium-99m-labeled red blood cells were performed in 52 consecutive patients to determine whether cinematic acquisition and display localized sites of bleeding more accurately than did conventional static imaging. Computerized images were obtained for 15 seconds per image in 15-minute sets. Interpretations based on a cinematic display were compared with those based on standard 1-minute images obtained every 5 minutes. Pathologic confirmation of a site of bleeding was obtained in 21 patients. The cinematic display demonstrated bleeding not seen on static images and yielded either more accurate localization or increased sensitivity in eight of 21 patients (38%). Linear regression showed that the cinematic correlation (r = .98) to the actual site of bleeding was better than either of two readers' interpretations of the static display (r = .93, P less than .02; and r = .88, P less than .0004). The mean error for cinematic localization of bleeding (0.4 anatomic segments +/- 0.6 [standard deviation]) was less than that for the static interpretations (1.1 anatomic segments +/- 1.4) (P less than .01). It is concluded that computerized cinematic acquisition and display of scintigrams improves localization and detection of gastrointestinal bleeding. PMID- 1523307 TI - Colorectal villous adenoma: transrectal US in screening for invasive malignancy. AB - Exclusion of focal infiltrating malignancy in colorectal villous adenoma is a prerequisite when nonsurgical treatment is considered. In a study of 81 patients with endoscopically identified colorectal villous adenoma screened for malignancy with transrectal ultrasonography (US), 15 patients were excluded because of incomplete follow-up. Twelve carcinomas were present, confirmed with either histopathologic examination after surgical resection (n = 9) or biopsies during laser treatment (n = 3). Nine of them were detected with transrectal US on the basis of disruption of the anatomic wall layers (sensitivity, 75%). In 46 of the 54 adenomas transrectal US helped confirm the benign nature of the lesion (specificity, 85%). Seven of the eight false-positive cases happened to be previously treated with surgery or coagulation. Treatment-associated inflammatory changes in the wall layers seemed responsible for this misinterpretation. Because of the high predictive value for a negative result (benign adenoma, 94%), transrectal US is recommended for the evaluation of villous adenomas to detect malignancy, especially when nonsurgical treatment is considered. Transrectal US should be performed before diagnostic polypectomy. PMID- 1523308 TI - Staging of cervical cancer: reliability of transrectal US. AB - One hundred twenty-four patients with invasive carcinoma of the cervix were examined with transrectal ultrasound (TRUS) before treatment. Since surgery preceded any other kind of therapy, sonographic findings could be compared with the surgical pathologic stage. The accuracy of staging with TRUS was 83%, compared with an accuracy of 78% for clinical staging performed according to the criteria of the International Federation of Gynecology and Obstetrics (FIGO). For extent of parametrial involvement, the sensitivity of TRUS evaluation was 78%, with a specificity of 89% and a diagnostic accuracy of 87%. The same reliability parameters for clinical evaluation were 52%, 92%, and 84%, respectively. From these data and from analysis of the cases--in which a discrepancy between clinical and TRUS staging was observed--it can be concluded that TRUS could be usefully applied to routine pretreatment evaluation of patients with cervical carcinoma. PMID- 1523309 TI - Myometrial invasion by endometrial carcinoma: assessment with plain and gadolinium-enhanced MR imaging. AB - A prospective study was designed to determine the sensitivity and specificity of nonenhanced T2-weighted and contrast material-enhanced T1-weighted magnetic resonance (MR) imaging in assessing the depth of myometrial invasion in patients with proved endometrial cancer. In 56 consecutive patients with clinically determined early-stage disease, findings of the two MR imaging techniques were compared with results of histologic examination of surgical specimens. Myometrial invasion was classified as absent (stage IA), superficial (stage IB), or deep (stage IC). In the assessment of each tumor stage, the sensitivity and specificity of contrast-enhanced T1-weighted MR imaging were higher than those of non-enhanced T2-weighted MR imaging. In determining the degree of myometrial tumor invasion, the overall sensitivity of enhanced T1-weighted MR imaging was 87.5%, whereas that of nonenhanced T2-weighted MR imaging was 71.4% (P less than .05). The use of contrast material may improve the ability to assess, with MR imaging, the depth of myometrial invasion by endometrial cancer. PMID- 1523310 TI - Limitations of liver surface US in the diagnosis of cirrhosis. AB - Ultrasound (US) of the liver surface with a high-frequency, small-parts, short focused probe has been proposed as a method of diagnosing cirrhosis. US of the liver was performed in 50 consecutive patients undergoing diagnostic liver biopsy to assess the clinical usefulness of this noninvasive procedure in diagnosing hepatic cirrhosis. Eight patients had histologically proved cirrhosis, and 42 had no histologic evidence of cirrhosis. Seven of the eight patients with cirrhosis had a normal liver surface at US, and five of the 42 patients without cirrhosis had an abnormal liver surface. US of the liver surface with this probe was not reliable in this heterogeneous patient population. PMID- 1523311 TI - The pelvis: T2-weighted fast spin-echo MR imaging. AB - Fast spin-echo (SE) T2-weighted magnetic resonance (MR) imaging provides images with highly T2-weighted contrast in substantially reduced imaging times. In a prospective evaluation, fast SE T2-weighted imaging of the pelvis was compared with conventional SE T2-weighted imaging in 30 consecutive patients in whom pelvic pathologic conditions were suspected. Three reviewers independently analyzed the images for (a) overall image quality, (b) pelvic organ definition, (c) conspicuity of pelvic fluid, and (d) conspicuity of pelvic pathologic conditions. Fast SE images were rated superior to conventional SE T2-weighted images in 60% (54 of 90) of the case reviews for overall image quality, in 69% (62 of 90) for pelvic organ definition, in 63% (57 of 90) for conspicuity of pelvic fluid, and in 68% (43 of 63) for conspicuity of pelvic pathologic conditions. The fast SE examinations were typically three to four times faster than conventional SE T2-weighted examinations. No pathologic findings seen on conventional SE T2-weighted images were undetected on fast SE images. Fast SE images may replace conventional SE T2-weighted images in MR imaging of the pelvis. PMID- 1523312 TI - Medial malleolar stress fractures in seven patients: review of the clinical and imaging features. AB - Stress fractures of the medial malleolus were discovered in seven patients, five male and two female subjects aged 16-34 years. All except one were involved in running and jumping athletic activities. Gradual onset of pain over the medial malleolus occurred with repetitive activity. Focal intense increased uptake in the medial malleolus was present on bone scans. Conventional radiography and computed tomography demonstrated the presence of subtle fissures at the junction of the medial malleolus and the tibial plafond, and well-circumscribed lytic lesions were also seen in three patients. Two patients developed a complete fracture of the medial malleolus. Stress fractures of the medial malleolus should be suspected in patients involved in athletic and/or unusual activities who have experienced persistent and unexplained pain over the medial malleolus. Bone scans and radiographs should be obtained for diagnostic purposes in these patients. PMID- 1523313 TI - Double injuries of the forearm: a common occurrence. AB - To evaluate the frequency of different types of forearm fractures and, in particular, determine the frequency of double injury to the forearm, the authors prospectively examined 119 consecutive forearm fractures and found double injuries to the forearm in all but five cases. In 79 of the 119 patients (66%), ligamentous injury was seen in addition to the obvious fracture. Nine patients with apparent isolated fractures on initial radiographs underwent examination by means of radionuclide bone scanning, which revealed a second injury in eight of them. Four patients with apparent single fractures did not undergo bone scanning because of their critical conditions. In four patients, a single fracture was initially diagnosed, but after reduction and casting, dislocation of the radioulnar joint was seen. These findings indicate that injury to the forearm almost invariably occurs at two or more sites and involves either both bones or bone and ligament. Because the distal radioulnar joint was affected in 71 patients (60%), scrutiny of the wrist is imperative whenever injuries to the bones of the forearm are discovered. PMID- 1523314 TI - Rheumatic and nonrheumatic disease in the temporomandibular joint: gadolinium enhanced MR imaging. AB - Magnetic resonance (MR) imaging of 36 temporomandibular joints (TMJs) in 27 patients and six healthy volunteers was performed before and after injection of gadopentetate dimeglumine. Twelve asymptomatic joints were used as controls, 12 TMJs had symptomatic internal derangement, and 12 TMJs had rheumatic inflammatory disease. A small or moderate joint effusion was seen in one asymptomatic joint, four joints with internal derangement, and one joint with rheumatic involvement; in all of these, contrast enhancement of the effusion was observed. A large effusion in one rheumatic joint was enhanced only after delayed imaging. In healthy controls and patients with internal derangement, no or only minimal enhancement of intraarticular tissues was seen. Eleven of the 12 rheumatic TMJs showed moderate or intense soft-tissue enhancement along the disk and articular surfaces (ie, in areas normally devoid of synovial membrane). The one rheumatic joint without enhancement had bony ankylosis and no remaining soft tissue within the joint space. Gadolinium-enhanced MR imaging of the TMJ may effectively depict the proliferating synovium of rheumatic inflammatory joint disease. PMID- 1523315 TI - Severity of aortic regurgitation: interstudy reproducibility of measurements with velocity-encoded cine MR imaging. AB - The interstudy reproducibility of velocity-encoded cine (VEC) magnetic resonance (MR) imaging for quantification of regurgitant volume (RV) and regurgitant fraction (RF) was studied in 10 patients with chronic aortic regurgitation. Each patient underwent two VEC MR imaging studies. RV and RF were measured on the aortic flow curve by quantifying antegrade and retrograde flow per cardiac cycle. VEC MR imaging measurements for RV and RF correlated closely with volumetric measurements for both studies (r greater than .97). Interstudy reproducibility for VEC MR imaging measurement of RV and RF was high (r greater than .97), and the interstudy variability for VEC MR imaging measurements was low. These results demonstrate a high accuracy of VEC MR imaging for measurement of RV and RF in patients with chronic aortic regurgitation. The level of interstudy reproducibility of VEC MR imaging for quantitative assessment of RV and RF indicates the potential of this technique for follow-up and monitoring of response to therapy. PMID- 1523316 TI - Three-dimensional motion and deformation of the heart wall: estimation with spatial modulation of magnetization--a model-based approach. AB - A method for in vivo estimation of the three-dimensional (3D) motion and deformation of the heart from tagged magnetic resonance images of the myocardium is presented. The method is based on a 3D deformable model fitted to the motion of tagged points in two views (short and long axes), which results in a comprehensive kinematic model of the dynamic geometry of the left ventricle. The method was applied to data obtained in four healthy volunteers, and data were pooled according to position within the model. Analytic modeling demonstrated that the calculated strain field was relatively invariant to the type of smoothing constraint applied; the greatest error was in the circumferential radial shear strain. Displacement, torsion, and strain extracted from the model agreed with previous results of two-dimensional MR imaging analyses and 3D studies involving the implantation of radiopaque beads in canine myocardium. The model-driven approach provides an accurate and flexible technique for noninvasive estimation of 3D in vivo deformation of the human heart. PMID- 1523317 TI - Aortic aneurysms: growth rates measured with CT. AB - Because of a lack of information about the rates of growth of aortic aneurysms, such rates in thoracic and abdominal aortic aneurysms were determined. One hundred seventy-one patients with atherosclerotic aortic aneurysm managed nonoperatively were followed up for more than 6 months with sequential computed tomography (CT). There were 211 aneurysms (thoracic aortic, 82; abdominal aortic, 129). The growth rates of thoracic and abdominal aortic aneurysms were 0.42 and 0.28 cm/y, respectively. Aneurysms at the aortic arch (n = 34) grew at a faster average rate (0.56 cm/y) than aneurysms arising at other levels, even when the rate was corrected for the initial diameter. It is recommended that thoracic aortic aneurysms, especially aortic arch aneurysms, be followed frequently with CT examination of size. PMID- 1523318 TI - Automatic film processing: analysis of 9 years of observations. AB - A survey method known as the sensitometric technique for the evaluation of processing (STEP) has been used to monitor processing speed of over 2,000 automatic film processors in hospitals, private offices, and mammography facilities since 1981. Analysis of data obtained through this program revealed underprocessing at 33% (76 of 231) of observed hospitals in 1987, 7% (13 of 179) of mammography facilities in 1988, and 42% (101 of 241) of private practices in 1989. Underprocessing at mammography facilities decreased from 18% (25 of 139) in 1985, which was contrary to the trend in hospitals. The consequence of underprocessing is higher radiation exposure and a degradation in film contrast. Evaluation of automatic film processors is a necessary part of any comprehensive evaluation of a diagnostic radiography facility. The STEP procedure was designed only as a field survey test; to ensure optimal conditions for obtainment of diagnostic quality radiographs, facilities should perform quality assurance evaluations of their processing equipment and verify that processing recommendations of manufacturers are being followed. PMID- 1523319 TI - Patent paraumbilical vein: anatomic and hemodynamic variants and their clinical importance. AB - Fifty-five of 353 patients with suspected portal hypertension studied with Doppler sonography had a patent paraumbilical vein. Of these 55 patients, 39 had the classic intrahepatic venous circulation found in Cruveilhier-Baumgarten syndrome: hepatopetal flow in all segmental portal veins and hepatofugal flow leaving the liver in a paraumbilical vein in the falciform ligament to join veins of the anterior abdominal wall. Sixteen patients had variants of the classic pattern: Flow in one or more segmental portal veins of the left lobe or the entire liver was hepatofugal. In addition, new venous channels connecting the left portal vein with the extrahepatic paraumbilical vein were found. Assessment of liver function with the Pugh score showed severe impairment in the majority of patients with a patent paraumbilical vein. Patients with the classic intrahepatic circulation had smaller esophageal varices than those with hemodynamic or anatomic variants. The presence of a patent paraumbilical vein did not prevent formation of esophageal varices in the patients studied. PMID- 1523320 TI - Access-site thrombosis after placement of inferior vena cava filters with 12-14-F delivery sheaths. AB - Inferior vena cava filters were placed in 60 patients. Ultrasound (US) of the venous access site was performed before and 3-5 days after filter placement to determine the prevalence of occlusive and nonocclusive access-site thrombosis (AST). Prevalence of symptoms attributable to AST was also evaluated at 1-month clinical follow-up in 58 of the 60 patients. All filters were placed with delivery sheaths with outer diameters of 12-14 F. US depicted development of occlusive AST in six of the 60 patients (10%). Nonocclusive AST developed in 15 (25%). Symptoms related to AST occurred in two of 58 patients (3%). There was a substantially increased prevalence of occlusive thrombus in patients in whom partially occluding thrombus or extrinsic compression in the inferior vena cava or ipsilateral iliofemoral veins was demonstrated on vena cavograms obtained before filter placement. The prevalence of both symptoms attributable to AST and US-detected occlusive thrombus in this series with smaller delivery systems is lower than that reported after percutaneous placement of stainless steel Greenfield filters via 29.5-F (outer diameter) sheaths. PMID- 1523321 TI - Fine-needle aspiration biopsy of abdominal lesions: diagnostic yield for different needle tip configurations. AB - Four fine-needle aspiration biopsy needles with different tip configurations were used in 133 patients with abdominal lesions. The 20-gauge needles were used in random sequence by several physicians. The specimen from each of the 522 needle passes was evaluated by two cytopathologists for adequacy to render a diagnosis and for the presence of cell block material. The Franseen needle produced a 16% and 9% better yield for diagnostic material than did the cut biopsy and spinal needles (P less than .05), respectively. The Westcott needle was better than the cut biopsy needle by 13%, and the spinal needle produced an 11% better yield than did the cut biopsy needle. Differences did not exist in liver biopsies but were present in pancreatic biopsies. The spinal needle was the least successful in yielding cell block material. Use of the cut biopsy needle resulted in the largest proportion of inadequate specimens, except its yield in cell blocks in the liver was 25% higher than that of the Westcott needle. The authors conclude that not all unusual designs for 20-gauge needle tips render results superior to those of the simple spinal needle. PMID- 1523322 TI - In vivo evaluation of iophendylate-cyanoacrylate mixtures. AB - Cyanoacrylate glue is a rapidly polymerizing agent used for vascular embolization. Polymerization occurs when the glue comes into contact with ions in the blood or on the vascular endothelium. Mixing iophendylate with cyanoacrylate causes slowing of polymerization, allowing flow-directed embolization into the nidus of an arteriovenous malformation (AVM) or the central neovascularity of a tumor or hemangioma. The authors attempted to define the relationship between the iophendylate-glue ratio and polymerization time with an in vivo swine model. In this model, glue setup occurred much more rapidly than predicted on the basis of in vitro studies. This appeared to be due to glue polymerizing on the endothelium at vessel bifurcations and at areas of acute angulation or marked vessel narrowing. On the basis of these data, the authors substantially increased the iophendylate-glue ratio in their most recent AVM embolization procedures and achieved nidus occlusion in each case. With use of the authors' guidelines, it is possible to achieve optimal distal flow-directed embolization with cyanoacrylate. PMID- 1523323 TI - Peripheral pulmonary nodules: preoperative percutaneous needle localization with CT guidance. AB - Despite recent advances in endoscopic surgical techniques, small nonpalpable peripheral pulmonary nodules may not be amenable to thoracoscopic resection. To facilitate resection in such cases, a technique of percutaneous needle localization involving use of a conventional mammographic needle localization system and computed tomographic guidance was developed. The technique has been used successfully in localization of 19 peripheral pulmonary nodules in 20 patients referred for thoracoscopic surgery. PMID- 1523324 TI - Preoperative needle localization of subtle breast calcifications: magnification technique. AB - The authors adapted a windowed needle localization compression plate to allow performance of mammography with magnification technique, facilitating preoperative needle localization of subtle breast calcifications. The technique has been successfully used in 20 needle localization procedures. PMID- 1523325 TI - Localization of breast lesions identified on one mammographic view: the skin pinch technique. AB - Mammographic abnormalities may occasionally be seen on only one view. With a simple method, preoperative needle localization of such clinically occult lesions can be performed. The technique involves use of the relative mobility of the skin and subcutaneous tissue of the breast compared with that of the more fixed parenchymal cone. Geometric ratios and changes in tube angulation are unnecessary with this approach. PMID- 1523326 TI - Dual-purpose tube for enteroclysis and nasogastric-nasoenteric decompression. AB - A catheter designed for the dual purpose of nasogastric-nasoenteric decompression and enteroclysis is described. The catheter facilitates direct decompression of the obstructed small bowel and, if necessary, subsequent performance of enteroclysis. The use of this tube obviates dual intubation and its accompanying discomfort. PMID- 1523327 TI - Potential therapeutic effect of oil-soluble contrast media in hysterosalpingography. PMID- 1523328 TI - Obtaining clinical information: a radiology problem with a computer-based solution. PMID- 1523329 TI - Increased incidence of cancer in a small subset of the population: a new obstacle to screening mammography? PMID- 1523330 TI - Preoperative needle localization. PMID- 1523331 TI - Evaluation of section sensitivity profiles and image noise in spiral CT. AB - Spiral computed tomography (CT) offers continuous volume scanning of complete organs or body sections within a single breath hold. Almost all image quality characteristics of spiral CT are identical to those of conventional section-by section CT; however, there is a change in pixel noise values and degradation in the shape of the section sensitivity profiles (SSPs). Computer simulations, phantom measurements, and clinical studies were used in evaluating the SSP and noise characteristics of two new section-interpolation algorithms. The results were compared with standard CT and spiral CT data processed with the commonly employed linear section-interpolation algorithm. Degradation of SSP quality was insignificant for a table feed distance per 360 degrees revolution equal to the section thickness when the new algorithms were applied; noise values, however, increased. SSP width increased for table feed distances greater than the section width, the effect being less pronounced with the new algorithms. The value of these algorithms is primarily seen in the improved quality of multiplanar reformations and cine and three-dimensional displays. PMID- 1523333 TI - Radiography of the lumbosacral spine: characteristics of examinations performed in hospitals and other facilities. AB - A survey of 523 facilities performing radiographic lumbosacral spine examinations was conducted as a part of the Nationwide Evaluation of X-Ray Trends program in 1987 and 1989. Average patient radiation exposure was measured by using a standard phantom developed by the Center for Devices and Radiological Health of the Food and Drug Administration, U.S. Public Health Service. Data pertaining to radiographic equipment, film processing, and radiographic techniques were obtained. The overall average entrance skin air kerma was 3.65 mGy (420 mR). Ninety-eight percent (496 of 506) of observed facilities used a grid, 89% (466 of 523) had tube potentials between 70 and 89 kVp, and 67% (280 of 418) used screen film systems with a speed of 400. The most important finding is that underprocessing of film remains a major concern. Thirty-three percent (78 of 234) of the hospitals, 25% of the radiologists in private practice (four of 16), 33% of the nonradiologist private practitioners (27 of 82), and 48% (69 of 143) of the chiropractors underprocessed their film. PMID- 1523332 TI - Minimum scan speeds for suppression of motion artifacts in CT. AB - Cardiac and ventilatory motions cause artifacts at chest computed tomography (CT). To determine how short the scan times on third-generation units must be to avoid such artifacts, motion was measured with fast and ultrafast CT scans. Minimum detectable motion was then determined. The longest scan time that avoided a barely perceptible artifact was calculated by dividing the minimum detectable motion by the peak physiologic velocity. The posterior left ventricular wall moved at a maximum velocity of 52.5 mm/sec, necessitating a scan time of 19.1 msec or less to avoid artifact. Lung vessels near the heart moved at 40.5 mm/sec for a scan time of 24.7 msec or less. During quiet breathing, pulmonary vessels moved at 10.7 mm/sec for a scan time of 93.5 msec or less. The authors conclude that the shortest scan time on third-generation units (0.6 second) cannot prevent all artifacts arising from motion in the chest. Even ultrafast scan times (50 msec) are not short enough to eliminate artifacts on these units. Thus, reduction of motion artifacts will require techniques other than fast scanning. PMID- 1523334 TI - Recruiting radiologists: the 1991 hiring survey. AB - Recent studies present widely varying views on the radiologist staffing situation, ranging from a projected surplus of over 6,000 radiologists to an estimated shortage of 5,000. To help clarify the situation, the American College of Radiology undertook a stratified random sample survey of radiology groups' recruitment efforts and hiring results in 1991. This survey of 192 groups achieved a 78% response rate. It found that half of all groups recruited, seeking to fill a nationwide total of 1,900 positions. Larger groups were more likely to recruit than smaller ones. Groups filled 1,348 (71%) of these positions, while 552 positions remained unfilled, which was 2.8% of groups' total staff. Remaining vacancies ranged from 5% of total staff in the Northeast and 3% in the Midwest to 2% in the South and 1% in the West. The percentage of positions filled was higher (76%) in nonmetropolitan areas than elsewhere. The authors conclude that the supply of radiologists is very close to balancing the number of positions available; the disparity is about 1/10 of some numbers mentioned previously and is probably shrinking. Also, recruiting is not less successful in nonmetropolitan areas and small cities than elsewhere. PMID- 1523335 TI - Deployment and utilization of MR imaging in Michigan: observations of a statewide data base. AB - Patterns of deployment and utilization of magnetic resonance (MR) imaging were studied with a Michigan Department of Public Health data base containing data regarding more than 218,000 patient visits. Michigan currently has 16 hospital based fixed MR systems (magnets), 14 (13 operational) freestanding fixed magnets, and 11 (10 operational) mobile magnets operating at 45 host sites. The imaging volume for 1991 was approximately 127,000 procedures, with associated charges of $126,500,000. Central nervous system imaging accounted for 82.6% of procedure volume, with extremities accounting for another 12.9%. The average total charge per procedure ranged from $844 to $1,076, and the average professional charge per procedure ranged from $178 to $226. The annual throughput ranged from 1,356 to 7,480 procedures per magnet. Wide variation in many measures was observed both within and among hospital-based, freestanding, and mobile facility types. The use of computed tomography (CT) before MR imaging for the same diagnostic problem continues to be substantial (average, 44% for MR imaging of the head). Patterns of inpatient imaging and prior use of CT indicate that the technical benefit of mobile MR imaging should be investigated further. PMID- 1523336 TI - Periocular lymphoproliferative diseases: natural history, prognostic factors, and treatment. AB - A study was undertaken to assess the natural history of periocular lymphoproliferative diseases, identify key prognostic factors, and clarify the role of orbital irradiation. Thirty-four patients with periocular lymphoproliferative disease were treated with orbital irradiation between 1975 and 1990. Eight patients had atypical lymphoid infiltrate, and 26 had malignant lymphoma. Forty-three eyes were irradiated with en-face electrons or 6-MV photons. Five-year disease-free survival for all stages was 65%; it was not significantly affected by bilaterality or site. Stage, distinction between atypical lymphoid infiltrate and malignant lymphoma, and working formulation grade were important prognostic indicators. A complete response during irradiation was achieved in 24 of 43 (56%) eyes at a median dose of 2,400 cGy, and a partial response was achieved in 19 (44%), with resolution at a median of 2.8 months. Patients with periocular reactive lymphoid hyperplasia or atypical lymphoid infiltrate may have or are at significant risk of developing lymphoma and dissemination. Local treatment remains important; orbital irradiation achieves prompt local control with acceptable morbidity. PMID- 1523337 TI - Optic neuropathy after irradiation of meningioma. AB - Radiation-induced optic neuropathy (RON) is a rare and catastrophic complication of currently employed radiation therapy regimens for meningiomas that have been partially resected and sampled for biopsy. Between 1972 and 1989, 49 patients received postoperative irradiation for partially resected or biopsy sampled meningiomas, with the optic nerve within the treatment field. One patient experienced RON. The latency period for this case was 23 months. A review of the literature disclosed few cases of RON after treatment for meningioma; however, 42 cases of RON have been reported after radiation therapy for other lesions. The authors constructed two approaches to predict optic nerve radiation tolerance. The first is modeled on a previous proposal for a neural tissue nominal standard dose term and enabled accurate prediction of safe treatment regimens and risk of RON. This approach compared favorably with previously employed nominal standard dose terms. The second approach, based on the linear-quadratic model, proved unsuccessful due to its failure to achieve statistical significance. PMID- 1523338 TI - Mammographic appearance following implant removal. AB - Potential complications of augmentation mammaplasty with silicone gel breast implants have been the subject of much recent debate in the medical and lay communities. Some women have undergone implant removal, and others may follow. The mammographic appearance following submammary implant removal in four women and the histologic appearance in one case are described. Bilateral symmetric soft tissue masses posterior to the glandular tissue with accompanying calcifications should suggest the diagnosis. The radiologist should be familiar with the mammographic appearance following implant removal. Such knowledge may prevent unnecessary concern and unwarranted biopsy. PMID- 1523339 TI - Efficacy of spot compression-magnification and tangential views in mammographic evaluation of palpable breast masses. AB - To define the role of special mammographic views in evaluating palpable breast masses, 70 consecutive women with palpable breast masses underwent standard two view examination of each breast and spot compression-magnification and tangential view examination of the palpable mass. Thirty palpable masses were found in 30 patients (43%). Standard views depicted 26 masses (87%). Tangential views also depicted 26 masses. Some of the masses seen on tangential views were not seen on standard views and vice versa. Spot compression-magnification views depicted 29 masses (97%). Special views thus depicted an additional 9% of palpable masses not seen on standard views (four of 44 cases). All lesions not seen on tangential views were central; the one lesion not seen on spot compression-magnification views was peripheral. Special views allowed correct prediction of benign or malignant status in 77% of cases (23 of 30), while standard views allowed correct prediction in 69% of cases (18 of 26). PMID- 1523340 TI - Chronic hypersensitivity pneumonitis: high-resolution CT and radiographic features in 16 patients. AB - To evaluate the manifestations of chronic hypersensitivity pneumonitis at radiography and high-resolution computed tomography (HRCT), findings in 16 patients with this disease were reviewed. To ensure objectivity, 50 patients with other chronic infiltrative lung diseases (fibrosing alveolitis [n = 29], sarcoidosis [n = 16], and miscellaneous conditions [n = 5]) were included. All patients had chronic disease with evidence of fibrosis at HRCT, as indicated by irregular linear areas and architectural distortion. Radiographs and HRCT scans were reviewed separately, in random order, and without knowledge of diagnosis. On radiographs and HRCT scans, the fibrosis in cases of hypersensitivity pneumonitis was situated predominantly in the middle lung zones or showed no zonal predominance. Lung apices and bases were relatively spared in all cases. The distribution of fibrosis in the transverse plane was random in seven cases, subpleural in six, and peri-bronchovascular in three. The distribution of fibrosis can allow distinction of chronic hypersensitivity pneumonitis from other causes of fibrosis in many cases. PMID- 1523341 TI - Differentiation of alveolitis and pulmonary fibrosis with a macromolecular MR imaging contrast agent. AB - The ability of macromolecular contrast agent (polylysine-[gadopentetate dimeglumine]) to allow differentiation of pulmonary fibrosis and alveolitis at magnetic resonance imaging was investigated. Lung damage was induced by means of left bronchial instillation of 200 micrograms of cadmium chloride. Rats were imaged 3 hours (early alveolitic stage, n = 5), 24 hours (late alveolitic stage, n = 5), and 8 days (fibrotic stage, n = 5) later. Rats imaged 3 hours after cadmium chloride instillation demonstrated a gradually increasing contrast enhancement over 45 minutes (from 314% +/- 110 to 476% +/- 69 over baseline [P less than .01]), indicating a leak of paramagnetic macromolecules from the intravascular into the extravascular spaces. Conversely, lung enhancement remained virtually constant after injection of contrast material in contralateral control lungs and in damaged lungs imaged 24 hours and 8 days after cadmium chloride instillation. Furthermore, the enhancement in the fibrotic lung was lower (170% +/- 50) than that in the alveolitic and control lungs (320% +/- 65 and 298% +/- 61, respectively), indicating a decrease in plasma volume in the fibrotic lung. A macromolecular contrast agent can facilitate the differentiation between the exudative and fibrotic phases of interstitial lung disease. PMID- 1523342 TI - MURCS association and hypothalamic anovulation. AB - A new case of MURCS association (mullerian duct aplasia, renal aplasia and cervicothoracic somite dysplasia) in an 18 year old patient is reported. In addition to other minor phenotypical features, hypothalamic chronic anovulation was documented. Basal concentrations of PRL, TSH, GH, F and E were within reference values for adult women. Challenges with TRH and ACTH evoked normal responses in terms of TSH and F respectively. Basal levels of LH and FSH and a LHRH stimulation test demonstrated dissociation of both gonadotrophins. Persistent progesterone values within follicular phase levels led us to the diagnosis of hypothalamic chronic anovulation which was confirmed by the induction of ovulation by clomiphene citrate. This finding shows the importance of a detailed endocrinological evaluation in patients with the MURCS association in order to prevent secondary disorders due to endocrinological impairment. PMID- 1523343 TI - [The Philadelphia chromosome 30 years later]. AB - We review the changing concepts regarding the nature of the Ph chromosome during the last thirty years. The role of molecular biology techniques in its identification are discussed as well as its present status in the diagnosis, prognosis and management of chronic myelogenous leukemia and acute lymphoblastic leukemia. PMID- 1523344 TI - [Clinico-pathological diagnostic agreement among 429 autopsies from the Instituto Nacional de la Nutricion Salvador Zubiran]. AB - Comparison of clinical and autopsy findings of the cases studied between 1984 and 1988, were made at the Department of Pathology of the Instituto Nacional de la Nutricion Salvador Zubiran in Mexico City. The goal was to determine the accuracy of clinical diagnoses. The total number of cases was 429. A decreasing number of autopsies as a function of time was observed. Thus, in 1985, 34.65% of the deaths was autopsied, whereas in 1988, the number dropped to 21.16%, overall mean of 27.31%. In 229 autopsies (53.8%), 353 findings of clinical significance were found; of these, 86 were in the main diagnoses and 267 in the causes of death. There were 171 overdiagnoses with therapeutic implications, 38 in the main diagnoses and 133 in the causes of death. Overdiagnoses and underdiagnoses were most common in infectious diseases, followed by respiratory and digestive diseases, while endocrinologic and rheumatologic diseases had the highest diagnostic concordance. It was also found that the diagnostic accuracy did not improve with time of hospitalization. A brief analyses of the probable causes of the decrease in the number of autopsies is made. It is concluded that, in spite of the great advances in clinical and technological knowledge, the high frequency of disagreements between clinical and anatomical diagnoses, indicate that autopsy continues playing a key role in the quality control of medical practice. This justifies by itself the performance of necropsies. PMID- 1523345 TI - [AIDS from transfusions in Mexico]. PMID- 1523346 TI - Nutritional status of a nationwide sample of rural Mexican populations. AB - Information on nutritional status of the rural Mexican population is mostly obtained from cross-sectional studies. This investigation evaluates semi longitudinally the nutritional level of a sample of the rural population of Mexico. A total of 15,552 individuals in 2,587 households from 208 rural communities were evaluated. Body weight and height of rural boys and girls were found to be significantly lower than in their urban counterparts. Severe forms of weight for age or height for age inadequacy were more frequent in females than in males, in smaller communities than in larger ones, and in economically depressed zones than in those with a good economy. Our data showed a lower frequency of mild and moderate forms of possible malnutrition than previous studies (20 vs 50%) using as a criterion weight for age. These differences are explained on the basis of sampling bias. PMID- 1523347 TI - [Plasma clearance of ethanol and its excretion in the milk of rural women who consume pulque]. AB - Women from rural areas of the central plateau of Mexico drink during pregnancy and lactation a mild alcoholic beverage called pulque as a galactogogue. Ethanol present in milk could have a harmful effect on growth and development of breast fed children. The purpose of this study was to quantify the ethanol consumed as pulque by eleven lactating rural women as well as its clearance rate in blood and milk. Mothers were separated in two groups depending upon the ethanol ingested in a single dose of pulque 0.21 +/- 0.08 g/kg of body weight (group A) and 0.44 +/- 0.11 g/kg (group B). Maximal concentration of ethanol was reached in milk at 60 minutes and almost equaled that in plasma. Both groups showed a similar clearance pattern regardless of the volume of pulque ingested. Clearance rates between groups were different: ethanol concentration in milk at 60 min were 8.4 +/- 3.0 mg/dL for group A and 26.2 +/- 7.0 mg/dL for group B. Two hours later ethanol levels were 3.6 +/- 3.4 mg/dL and 23.3 +/- 9.4 mg/dL respectively. Clearance rates were slower in mothers showing the highest concentration of ethanol in milk. The present data demonstrate that there is no differential elimination of ethanol in maternal blood and milk following ingestion of a moderate amount of pulque during lactation. The amount of ethanol received by infants through milk is relatively low and therefore it is unlikely to have harmful effects on them. Pulque consumption adds about 350 kcal/day to the customary dietary intake of these lactating women. PMID- 1523348 TI - [Antibodies against human T-cell lymphotropic viruses in subjects at high risk for HIV in Monterrey]. AB - HIV and HTLV-1 are retrovirus that can produce human disease. It is known that HTLV-1 is associated to the adult T cell leukemia and to the spastic tropical paraparesis. AIDS is now a pandemic infection and HTLV-1 has a high endemicity in the Caribbean region and Japan, whereas the south of the United States has a low endemicity. In Mexico there is little information on HTLV-1 incidence. In the present work we looked for anti HTLV-1 antibodies in one hundred persons that belong to the high risks AIDS population in the city of Monterrey, Mexico. We found that 93 sera were positive for anti HIV antibodies in a ELISA test and seven were negative. All 93 sera were also positive in the Western Blot assay. In the confirmatory test two out of the seven negative sera were classified as indeterminate and five as negative. We also included in this study 50 sera from healthy control volunteers that did not belong to the high risk AIDS population and resulted negative in the HIV and HTLV-1 test. Anti HTLV-1 antibodies were determined by using an agglutination test with gelatin particles covered with HTLV-1 and confirmed by a Western Blot assay. We found that only three sera resulted positive in this agglutination test, but were negative by the Western Blot technique. PMID- 1523349 TI - [Oral pathology in 161 asymptomatic and symptomatic HIV-positive patients]. AB - The aim of this study was to establish the prevalence of oral manifestations in HIV-infected patients and to correlate their frequency with the clinical stage. One hundred and sixty one HIV-positive individuals were examined, of whom 64 (40%) were in stages CDC-II and III and 97 (60%) in stage CDC-IV. The patients were examined at the AIDS out-patient clinic of the Instituto Nacional de la Nutricion Salvador Zubiran. The oral exams were performed by three examiners who were intra and inter calibrated, so that standard clinical criteria were followed. One hundred and twenty five patients (78%) showed one or more oral lesions. The proportion of patients with oral lesions increased significantly (p less than 0.05) according to the severity of the infection. Hairy leukoplakia (40%) and erythematous candidiasis (31%) were the most frequent lesions. When the prevalence of the different oral lesions was compared between the patients at early stages with the patients at the late stage no significant differences were found; only the pseudomembranous candidiasis and the exfoliative cheilitis were found with significantly higher values at stage CDC-IV than at earlier stages (p less than 0.001 and p less than 0.05 respectively). No association was found between oral candidiasis and tobacco use or xerostomia. Our study demonstrates that the prevalence and clinical features of the oral manifestations found showed similarities with those reported in other countries, but ulcero-necrotizing gingivitis was not found in our patients. PMID- 1523350 TI - A controlled trial of pravastatin vs probucol in the treatment of primary hypercholesterolemia. AB - We compared the safety, tolerability and efficacy of the HMGCoA reductase inhibitor pravastatin and probucol in the treatment of patients with primary hypercholesterolemia using an active, drug controlled, double blind, randomized, double placebo design. Patients were included if LDL-C levels after a minimum of six weeks on an AHA phase I diet were greater than 150 mg/dL and triglycerides were less than 350 mg/dL. Included patients were randomly assigned to either pravastatin 40 mg pm or probucol 500 mg bi. They also received matching placebos for each drug. The active drug period lasted 16 weeks, during which the patients were seen at 4, 8, 12 and 16 weeks after baseline. There were no significant differences in baseline values between both treatment groups. Significantly lower values of total cholesterol and LDL-C were observed with pravastatin as compared to probucol. While a non significant increase of HDL-C was observed with pravastatin, a remarkable and statistically significant decrease was observed with probucol. A large dispersion of triglycerides levels was observed with both drugs and no statistically significant changes were demonstrated. Both pravastatin and probucol were well tolerated: only minimal clinical and laboratory changes, not considered to have been drug-related, were observed. No changes, considered drug-related, were observed in the cristalline lens. This study shows an overall superiority of pravastatin over probucol with significant larger decreases of total cholesterol and LDL-C and a better effect on HDL-C. PMID- 1523351 TI - [Comparison of 2 chemotherapy protocols in adult acute myeloblastic leukemia. Results of the Instituto Nacional de la Nutricion Salvador Zubiran cooperative group]. AB - Up to now, the best treatment for patients with acute myelogenous leukemia (AML) is the induction of bone marrow hypoplasia by ablative combined chemotherapy; the prototype of these schedules is the so-called 7 + 3 (seven days of continuous infusion of cytarabine and three days of one-hour infusion of any anthracycline); these schedules require the support of both platelet transfusions and antibiotics. Other non-ablative schedules have also been tried in the treatment of such patients. Here we analyze the results of the treatment of 76 adult patients with AML; 43 were treated with the classical 7 + 3 schedule, whereas 33 were treated with a combination of chemotherapy used in non-ablative doses (TADOP: thioguanine, arabinosyl-citosine, doxorrubicin, vincristine and prednisone). The results were as follows, respectively, for 7 + 3 and TADOP: complete remission (CR) was achieved in 60 and 48% of patients (p NS); the number of cycles to achieve CR had a median of 1 and 5 months (p less than 0.001); the median duration of the CR was 21 and 10 months (p less than 0.05); fatal myelotoxicity was 30 and 42% (p NS), one-year disease free survival (DFS) was 45 and 46% (p NS) and three-year survival was 22% and 15% (p NS). Additionally, patients treated with 7 + 3 were divided into two groups according to the type of platelet transfusion support; those supported with apheresis equipment and those with centrifugation-derived platelets.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1523352 TI - Combination daytime chlorpropamide-metformin/bedtime insulin in the treatment of secondary failures in non insulin dependent diabetes. AB - OBJECTIVES: To determine the effectiveness of the combination therapy with daytime chlorpropamide-metformin and bedtime NPH insulin in the treatment of secondary failures in NIDDM and to study its effects on insulin secretion. DESIGN: Non randomized open study with a duration of two months. The patients were followed six months after ending the study. INSTITUTION: Department of Diabetes and Lipid Metabolism. Instituto Nacional de la Nutricion "Salvador Zubiran", Mexico City. CHARACTERISTICS OF THE PATIENTS: Nine patients (seven women and two men) were included. All had NIDDM and secondary failure to antidiabetic oral drugs. Their fasting plasma glucose was 14.5 +/- 2 mM/L and their HbA1c 13.37 +/- 2.9%. At the entry and at the end of the study a 5h-OGTT was done with assays of plasma glucose and C-peptide. TREATMENT: Chlorpropamide (375 mg/day) plus metformin (1200 mg/day) and bedtime insulin (0.1 U/kg/day). RESULTS: After two months on combination therapy, fasting plasma glucose and HbA1c levels were remarkably improved (decreases of 7.3 +/- 0.6 and 9.1 +/- 1.02 respectively, p less than 0.002). The insulin dose was small (6.77 +/- 2.09 U/day). Side effects were minimal and infrequent. During the 5h-OGTT, the mean glucose area under the curve also decreased. The insulin secretion did not change but the C-peptide/glucose ratio increased. At the end of the study, the insulin dose was tapered off and stopped when possible. The four patients with the best glycemic control during the study were able to suspend the bedtime insulin and maintain a good control six months after the insulin suspension. CONCLUSIONS: The combination therapy is useful in the treatment of secondary failures in NIDDM: Its advantages are the very low mean daily insulin dose needed, the low incidence of side effects and, if a HbA1c less than 8.7% is achieved, the restoration of oral antidiabetic drugs efficacy. The very low insulin dose used in this study could be explained by complementary effects of metformin and bedtime insulin on hepatic glucose output and a putative decrease in peripheral resistance attributable both to sulfonylurea and metformin. PMID- 1523353 TI - [Efficacy and tolerance to acarbose in non-insulin-dependent diabetics]. AB - Oral acarbose, a competitive inhibitor of alpha-glucosidase, has been shown to be effective in decreasing the postprandial rise in blood glucose and insulin. A double blind, cross-over, placebo controlled, randomized study in poorly controlled, non-insulin dependent diabetic patients under treatment with sulfonylureas was carried out. The patients continued receiving sulfonylureas throughout the study period and were randomly allocated into two sequences. In sequence A they received 100 mg tablets tid during 12 weeks; placebo tid during 2 weeks (wash-out period) and finally they were crossed over to placebo tid during 12 weeks. In sequence B, they received placebo tid 12 weeks, placebo tid during 2 weeks and finally acarbose 100 mg tid during 12 weeks. Sixteen patients were included in each sequence; three were excluded from sequence A, one because of side effects, one because of severe neuropathy and one because of change of address. One was excluded from sequence B because of failure to take the sulfonylurea. A slight but statistically significant decrease in weight was observed with acarbose as compared with placebo in both sequences. Significant reductions in postprandial glucose were observed in both sequences with acarbose. Significant reductions in fasting blood glucose were also observed in some visits. Although lower mean values of triglycerides and HbA1c were observed with acarbose, they were not statistically significant. Acarbose had side effects almost in all patients, but decreased on continued therapy. Only one patient had to be excluded for this cause. Acarbose is a useful therapeutic resource in poorly controlled non-insulin dependent diabetic patients in combination with sulfonylureas. PMID- 1523354 TI - [Observer agreement in the measurement of leg length]. AB - The lower limb length measurement is an important element for the diagnosis of mechanical or structural lumbar pain. Also it has been used for referral pain associated with hip or knee osteoarthritis or the groin and suprapubic areas. The aims of the present study were: 1) to measure the intra and inter observers variation; 2) to measure the intra-method variation using two different techniques for lower limb length measurement, one called the "apparent measure" (9) and comparing both with the radiological measurement technique. Two medical doctors, training on the techniques for lower limb measurement, performed the measurements. The exclusion criteria were flexion deformity of the hip or an overweight greater than 20% over the mean weight expected according to age and sex. A correlation coefficient and its 95% confidence interval (CI) were estimated, one tail test (Ho: r = 0.75). Seventeen patients fulfilled the inclusion criteria, 15 females and two males. The mean age was 35.8 years +/- 13.0 (SD). The correlation coefficient for the inter-observers variation using the "apparent measure" was 0.99 (CI = 0.985) and for the difference between legs it was 0.88 (CI = 0.10). The inter-observers variation for lower limb length measurement using the technique of "real measure" showed a correlation coefficient of 0.77 (CI = 0.95) and for the difference in length between legs it was 0.99 (CI = 0.85). The intra-observer correlation coefficient was 0.95 (CI = 0.85). The correlation coefficient for the inter-observer using the X-ray pictures was 0.98 (CI = 0.92).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1523355 TI - [Interaction of the cytoskeleton of E. histolytica with human erythrocytes]. AB - The mechanism by which trophozoites of E histolytica destroy mammalian cells has been correlated with the polymerization of the actin contained in the amoeba's cytoskeleton. This is preceded by the attachment of the amoeba lectins with carbohydrates in the cell surface. Here we describe the events of the interaction of E histolytica cytoskeleton with human red blood cells using fluorescence microscopy of glutaraldehyde-fixed trophozoites membrane removed with triton X 100 and stained with rhodamine-phalloidin. The challenge with RBC revealed a maximum polymerization two minutes after the challenge. The most active phagocytosis was observed four minutes after challenge. The use of fluorescent phalloidin showed to be a fast method which specifically binds to the F form of actin; this method is easier than methods which use monoclonal antibodies to identify actin. PMID- 1523356 TI - [4 cases of annular pancreas at the Instituto Nacional de la Nutricion Salvador Zubiran]. AB - Annular pancreas (AP) is a rare congenital anomaly due to malrotation of the pancreatic ventral yolk. Although it has been described in young and middle age adults it predominates in children. Its clinical picture is that of duodenal obstruction or acute pancreatitis episodes. In this paper we report four cases of AP that were seen at the Instituto Nacional de la Nutricion Salvador Zubiran in Mexico City. Three were females and three were less than twenty years old. In one case the diagnosis was established at birth and the operation done in another hospital. In another patient a diagnosis of pyloric hypertrophy was made and a pyloroplasty was performed. This young man was admitted in our hospital because of abdominal pain and hyperamylasemia. An eighty four year old woman was seen due to abdominal pain, nausea and vomit. In all cases the diagnosis of AP was carried out with radiological studies and confirmed by laparotomy. Surgical procedures consisted of duodenal-duodenal anastomosis in two, sphincteroplasty in one, and gastrojejunoanastomosis in the other. Two patients are asymptomatic, one died in the postoperative period, and one was lost for follow up. These four cases represent all the experience of our institute and correspond to one case in 36,735 admissions. PMID- 1523357 TI - Pathology of renal transplantation. AB - Renal transplantation is the most appropriate form of treatment for end-stage renal disease in all age groups. We present the experience of two hospitals in the pathology of kidney allograft. Renal biopsy is the most adequate method for the follow-up of these patients, because it permits the differential diagnosis of acute and chronic rejection, transplant glomerulopathy, recurrent and "de novo" glomerulonephritis and immunosuppression nephrotoxicity, mainly by cyclosporine A. We present the pathology features of all these entities, and study the representativity of the biopsy for diagnosis of rejection. The actuarial survival of the graft is 82% and 71% at 1 and 5 years, respectively. PMID- 1523358 TI - The role of histopathology in hepatic transplantation. AB - In hepatic transplantation, the recipient and the graft must manage a difficult symbiosis. The causes that can unbalance the mutual adaptation are various, but the clinical-biochemical hepatic graft syndromes they produce are not specific. Morphological study of the graft shows a distinct pattern for each type of dysfunction etiopathogeny. Such study may find: (1) immune attack: acute rejection or chronic rejection; (2) technical complications in the biliary tract or in the blood perfusion of the graft; (3) nonspecific cholestasis secondary to graft cold ischemia or preceding development of chronic rejection; (4) recurrence of the previous illness: graft infected by hepatitis virus; (5) opportunistic viral infections (cytomegalovirus, Epstein-Barr virus, herpesvirus, adenovirus); (6) reactions to drugs and toxics; and (7) combinations of several etiologies. Morphological knowledge enables the pathologist to collaborate in hepatic transplantation programs: elaborating protocols, selecting patients, diagnosing hepatic graft dysfunction, and assessing program quality. PMID- 1523359 TI - Pathology of lung transplantation. AB - The pathology of lung transplantation has many features in common with other solid organ grafts. Acute pulmonary rejection is characterized by perivascular, peribronchiolar, and interstitial mononuclear infiltrates. Chronic rejection causes obliterative bronchiolitis and vascular sclerosis. The transplanted lung is uniquely susceptible to infections, both usual and opportunistic, and these can be difficult to differentiate from rejection. Infection in the foreign graft can produce unusual histological appearances. Posttransplant lymphoproliferative disease can affect the lung allograft primarily. Transbronchial lung biopsy and bronchoalveolar lavage are considered essential to the postoperative management of lung transplants and to the understanding of the pathological processes limiting graft survival. PMID- 1523360 TI - Pathology of bone marrow transplantation. AB - For evaluating the therapeutic approaches in the follow-up and complications of patients treated with bone marrow transplantation (BMT), the histopathology is important on many occasions. The authors describe the different morphological changes that have an important role for treatment of these patients, classified according to their target organs of localization: skin, digestive tract, liver, and bone marrow. Graft-versus-host disease (GVHD) mainly affects the skin, gastrointestinal tract, and liver, and is sometimes difficult to differentiate from radiochemotherapy or infectious diseases. In the liver, the most frequent complications are GVHD, veno-occlusive disease, and infections. In the bone marrow, it is most important to evaluate the elimination of hemopathy and the reconstitution of normal hematopoiesis. PMID- 1523361 TI - Fine-needle aspiration biopsy in transplantation pathology. AB - Invasive methods are the only reliable method for diagnosis of rejection and other intragraft complications. Needle biopsy (NB) histology is considered as the "gold standard," but because of potential complications, cannot be used for frequent monitoring of organ allografts. Fine-needle aspiration biopsy (FNAB) is an invasive, but less traumatic, diagnostic method for continuous monitoring of intragraft events. The FNAB method makes it possible to evaluate the onset, intensity, and duration of inflammatory episodes of acute rejection. Parenchymal changes in the FNAB specimens give additional information of the intragraft events. As FNAB can be repeated daily, it enables not only diagnosis of the presence or absence of acute rejection, but can also monitor the effect of immunosuppressive therapy and the response to antirejection treatment. However, the diagnosis of chronic rejection and other later complications is established only by biopsy histology. PMID- 1523362 TI - Pathology of heart transplant through endomyocardial biopsy. AB - Cardiac transplantation is most effective method for treatment of patients with end-stage heart disease. We present the experience of our institution with 1,564 biopsies and 11 autopsies of 105 orthotopic heart transplants. This report describes the morphological features and the grading systems of acute rejection. Also, we present the morphological characteristics of other complications of heart transplants such as chronic rejection, "Quilty" effect, interstitial fibrosis, heart hypertrophy, previous biopsy sites, calcification, cytomegalovirus infections, toxoplasmosis, and the appearance of malignancies, mainly, lymphomas. Actuarial survival of patients is 91% and 88% at 1 and 5 years' posttransplant, respectively. PMID- 1523363 TI - Cancer rehabilitation: a consumer perspective. AB - Twenty years ago, quantity took precedence over quality of life as a matter of necessity. The idea of incorporating rehabilitation programs into the oncology arena was essentially a foreign concept. Quality-of-life issues are receiving more attention because of the survivorship movement; however, the ramifications for surviving the cancer experience in our current culture extend far beyond the medical diagnosis and treatment. PMID- 1523364 TI - Cancer rehabilitation: an overview. AB - Cancer rehabilitation is a practical attempt to maximize independence and dignity and to reduce the extent to which cancer interferes with an individual's physical, psychosocial, and economic functioning. The rehabilitation process should begin at the time of diagnosis or definitive medical intervention and should continue until the individual is able to maintain the desirable level of independence. PMID- 1523365 TI - Life cycle issues affecting cancer rehabilitation. AB - Developmental stage of the person with cancer has a profound effect on the rehabilitation plan. Although the issues faced by the very young and the elderly are quite different, the struggle to maintain optimal function is universal. As we continue to see improved survival rates and cures, the need for comprehensive rehabilitative care for all persons experiencing cancer becomes a challenge. Our success in meeting this challenge will be realized in measurable outcomes that will direct future rehabilitative care. PMID- 1523367 TI - The status of psychosocial research in the rehabilitation of the cancer patient. AB - This article has tried to describe the current status of psychosocial research in the rehabilitation of the cancer patient. It attempted to weave together the author's perspective of how decisions early in the history of sponsored research programs, particularly by the National Cancer Institute, combined with a limited knowledge base led to limited growth of the Rehabilitation Program. Thus, the current status of psychosocial cancer rehabilitation can be reasonably attributed to the decision at the National Cancer Institute to encourage the development of cancer rehabilitation services, rather than to aggressively expand the knowledge base. Although, in retrospect, it is possible to criticize these decisions, in fact, they were legitimate choices among a wide range of options. It was also not possible in this article to discuss many topics in psychosocial cancer rehabilitation, particularly differences in psychosocial adjustment as a function of type of cancer. What the study attempted to do was to confront the impression that cancer rehabilitation, in general, and psychosocial cancer rehabilitation, in particular, are ancillary activities that can receive a secondary level of resource allocation and support. The point was made that determining if psychosocial rehabilitation is possible raises as many basic research questions as does understanding how chemotherapy works or how a malignancy develops. All three areas ask legitimate basic research questions on how the body works and how behavior changes. Today, 10 years after the start of the original Rehabilitation Program, psychosocial cancer rehabilitation is an established field of study and an integral part of most major oncology services. Now, as stated, what is needed is an expansion of its knowledge base. Some of the issues that are deserving of support include studies on cosmesis, to what extent voluntary processes can compensate loss in speech and swallowing functions, functional evaluation following alternative surgical procedures, what is the quality of life following long-term survival of cancer, what are the group dynamics following return of a cancer patient to a work site, and so on. Each of these research questions can be guided by the same model developed for cancer control research by Greenwald and Cullen. Other more general approaches include recognizing and promoting the preventative dimension of cancer rehabilitation and developing the art and practice of psychometric assessment of psychosocial aspects of cancer rehabilitation, just to name two such areas. The American Cancer Society also recently sponsored a meeting to review and set new directions for psychosocial rehabilitation research.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1523366 TI - Functional rehabilitation in cancer care. AB - The most frequent difficulties that cancer patients face are physical problems, thus, evaluating the functional level of the patient is the cornerstone of rehabilitation. The Functional Independence Measure (FIM) measures self-care, sphincter control, mobility, locomotion, communication, and social cognition. PMID- 1523369 TI - Rehabilitation resources within the team and community. AB - The resources of a cancer rehabilitation team can provide the support, skills, and information needed whether the individual's life expectancy is short or long. The setting of such services must include both the inpatient and outpatient settings and serve as a comprehensive approach to enhance the survival for the patient with cancer. PMID- 1523368 TI - Vocational rehabilitation of cancer patients. AB - Indeed, cancer patients do face job discrimination. Empirical studies have shown evidences of personnel selection bias and many other work-related problems. Laws and legislation are good tools but are not the answers to most of the problems. A competent multidisciplinary rehabilitation team, a well-educated general public and employers, together with empowered cancer patients can do more towards eliminating destructive road blocks to the employment of the employable. This takes time and initially may be costly for all concerned. However, evidence has shown that the cost of closed cancer rehabilitation cases is the lowest per case for all occupational disabilities including tuberculosis, diabetes, mental disorders, heart disease, and orthopedic problems. In short, we dare not forget the simple truth put forth by Harold Dodds that "No, work is not an ethical duty imposed on us from without by a misguided and outmoded Puritan morality; it is a manifestation of man's deepest desire that the days of his life shall have significance." Cancer patients living with cancer desire significance to their days to the same degree that those of us who are healthy and well desire and need it. PMID- 1523370 TI - Future directions in cancer rehabilitation. AB - Many of the current and future directions in cancer rehabilitation have been briefly discussed; and some of the important areas for development are outlined in Table 1. Implementation of rehabilitation measures may be facilitated by organized and creative multidisciplinary rehabilitation programs. Advances are also dependent on health care policy, particularly in reimbursement for rehabilitation services and in the funding of rehabilitation research. Much progress can be expected in the years ahead. PMID- 1523371 TI - Minimally invasive urology. I. PMID- 1523372 TI - Microsurgical vasovasostomy under local anesthesia: an outpatient setting. PMID- 1523373 TI - Injectable prosthetic materials for the management of reflux and urinary incontinence in children. PMID- 1523374 TI - Use of endoluminal ultrasound of the ureter. PMID- 1523375 TI - [Work conditions at the hospital to be cross-examined]. PMID- 1523376 TI - [A nurse's day in the galleys]. PMID- 1523377 TI - [Abuse comes out from the shadows]. PMID- 1523378 TI - [The damage of distilbene]. PMID- 1523379 TI - [The obligation to vaccinate against the hepatitis B virus in question]. PMID- 1523381 TI - [Management of a severely burned patient]. PMID- 1523380 TI - [Gastric fibroscopy]. PMID- 1523382 TI - [The suffering is also psychic]. PMID- 1523383 TI - [Dressing care in the severely burned patient by the patient care team]. PMID- 1523384 TI - [For burns without sequela]. PMID- 1523385 TI - [Notebooks of the hospitalization of a burned patient]. PMID- 1523386 TI - [The nurse, medicines and her responsibility]. PMID- 1523387 TI - [Psychosociology and work relations]. PMID- 1523388 TI - [Nurses in the Kingdom of Mickey]. PMID- 1523389 TI - [The birth of legislatively assisted bioethics]. PMID- 1523390 TI - [The principle of culpability. Interview by Christian Moguerou]. PMID- 1523391 TI - [Hip! Hop! Public health]. PMID- 1523392 TI - [Blood culture]. PMID- 1523393 TI - [The blood culture system: Dupont Isolator]. PMID- 1523395 TI - [Use of perfusion solutions]. PMID- 1523394 TI - [When the law institutes a falsehood]. PMID- 1523396 TI - [The spinal column of athletes]. PMID- 1523397 TI - [Cochlear implants in children]. PMID- 1523398 TI - Good practice in decentralized analytical clinical measurement. PMID- 1523399 TI - Chromium exposure assessment of outdoor workers in Hudson County, NJ. AB - A large quantity of chromate chemical production waste, containing hexavalent chromium, has been used as fill at over 150 sites in Hudson County, New Jersey. One site is in a state park, and several other sites are adjacent to the park. Blood and urinary chromium levels were compared between 17 employees at the Hudson County park and 35 employees from two other state parks. A limited number of soil and personal air samples were also taken. Urinary and RBC chromium levels between the two groups were similar, even after adjusting for potentially confounding variables. The air sampling results demonstrated slightly higher chromium levels at Hudson County, but these were still very low level in nature (mean = 0.18 micrograms/m3). These results call into question the utility of chromium biomonitoring under environmental exposure conditions. PMID- 1523400 TI - The impact of the banning of tributyltin-based antifouling paints on the Sydney rock oyster, Saccostrea commercialis. AB - Two years after the banning in New South Wales (Australia) of tributyltin (TBT) based antifouling paints for vessels under 25 metres in length, the impact on the Sydney rock oyster, Saccostrea commercialis, has been assessed. Reduced growth and shell deformities present before banning were found to be absent and healthy oysters contained TBT at concentrations close to the detection limit of 0.2 micrograms Sn kg-1. High tissue concentrations of both copper and zinc, prior to banning were also significantly reduced. This behaviour was predicted by field experiments which showed that TBT had a synergistic effect on the uptake of copper. The distribution of both TBT and copper in the various organs of the oyster were examined in an attempt to explain this synergism. PMID- 1523401 TI - Pesticide exposure and cholinesterase levels among farm workers in the Republic of South Africa. AB - A preliminary survey was undertaken to establish the extent of pesticide exposure in a farming community. The area under investigation included a coffee plantation in the northern region of South Africa. Cholinesterase levels in red blood cells and plasma were used as markers to monitor the extent of organophosphate and carbamate exposure. Sixty-nine farm workers with specific pesticide exposure were selected for the study, and the frequency of the different symptoms which may be related to pesticide exposure was determined by interview and questionnaire. Of the workers, 77% had their red blood cell cholinesterase levels below the normal reference range, while 27% of the workers had depressed plasma cholinesterase levels. PMID- 1523402 TI - Arsenic lipids in the digestive gland of the western rock lobster Panulirus cygnus: an investigation by HPLC ICP-MS. AB - The digestive gland of the western rock lobster, Panulirus cygnus, was shown to contain phosphatidylarsenocholine and a phosphatidyldimethylarsinylriboside by HPLC ICP-MS examination of lipid materials rendered water-soluble by hydrolysis. Water-soluble arsenic material in the digestive gland was chiefly arsenobetaine but the deacylated analogue of the phosphatidyldimethylarsinylriboside and an unidentified compound were also present. PMID- 1523403 TI - AIDS vaccines. Testing target date looms, but will the vaccines be ready? PMID- 1523405 TI - User-friendly chemistry takes center stage at ACS meeting. PMID- 1523404 TI - Crime conference. Back to the drawing board, says NIH. PMID- 1523406 TI - One-pot biochemical cookery. PMID- 1523407 TI - Exons as microgenes? PMID- 1523408 TI - Carnivorous plants: phylogeny and structural evolution. AB - The carnivorous habit in flowering plants represents a grade of structural organization. Different morphological features associated with the attraction, trapping, and digestion of prey characterize a diversity of specialized forms, including the familiar pitcher and flypaper traps. Phylogenetic analysis of nucleotide sequence data from the plastic rbcL gene indicates that both carnivory and stereotyped trap forms have arisen independently in different lineages of angiosperms. Furthermore, these results demonstrate that flypaper traps share close common ancestry with all other trap forms. Recognition of these patterns of diversification may provide ideal, naturally occurring systems for studies of developmental processes underlying macromorphological evolution in angiosperms. PMID- 1523409 TI - Oxidized redox state of glutathione in the endoplasmic reticulum. AB - The redox state of the endoplasmic reticulum (ER) was measured with the peptide N Acetyl-Asn-Tyr-Thr-Cys-NH2. The peptide diffused across cellular membranes; some became glycosylated and thus trapped within the secretory pathway, and its cysteine residue underwent reversible thiol-disulfide exchanges with the surrounding redox buffer. Glycosylated peptides from cells were disulfide-linked to glutathione, indicating that glutathione is the major redox buffer in the secretory pathway. The redox state of the secretory pathway was more oxidative than that of the cytosol; the ratio of reduced glutathione to the disulfide form (GSH/GSSG) within the secretory pathway ranged from 1:1 to 3:1, whereas the overall cellular GSH/GSSG ratio ranged from 30:1 to 100:1. Cytosolic glutathione was also transported into the lumen of microsomes in a cell-free system. Although how the ER maintains an oxidative environment is not known, these results suggest that the demonstrated preferential transport of GSSG compared to GSH into the ER lumen may contribute to this redox compartmentation. PMID- 1523410 TI - NMR determination of residual structure in a urea-denatured protein, the 434 repressor. AB - A nuclear magnetic resonance (NMR) structure determination is reported for the polypeptide chain of a globular protein in strongly denaturing solution. Nuclear Overhauser effect (NOE) measurements with a 7 molar urea solution of the amino terminal 63-residue domain of the 434-repressor and distance geometry calculations showed that the polypeptide segment 54 to 59 forms a hydrophobic cluster containing the side chains of Val54, Val56, Trp58, and Leu59. This residual structure in the urea-unfolded protein is related to the corresponding region of the native, folded protein by simple rearrangements of the residues 58 to 60. Based on these observations a model for the early phase of refolding of the 434-repressor(1-63) is proposed. PMID- 1523411 TI - Attention-based motion perception. AB - Two "attentive" tracking tasks reveal the existence of an attention-based motion process. In the first task, oppositely rotating luminance and color gratings were superimposed. Because of masking from the color grating, the bars of the luminance grating were not visible; nevertheless, their motion was visible and it determined the perceived direction of the stimulus rotation. On the other hand, the bars of the color grating were visible but they could only be seen to move (in the opposite direction to the overall stimulus rotation) when they were tracked with attention. In a second task, the perceived velocity of a color grating, typically slow at equiluminance, speeded up when individual bars were attentively tracked. These findings demonstrate two independent motion processes: one that is "low-level" or automatic in that it signals motion even in the absence of attention to the stimulus, and one that is mediated by attention to visible features and provides accurate velocity judgments independently of the features being tracked. PMID- 1523412 TI - The origins of positron emission tomography. AB - The development of positron emission tomography (PET) took place through the combination of the following recognitions: (1) a handful of short-lived, positron emitting radionuclides, carbon-11, nitrogen-13, and oxygen-15, exhibit chemical properties that render them particularly suitable for the tracing of important physiological pathways, and (2) the radiation emitted as a result of the annihilation of positrons in matter exhibited physical properties that made it well-suited for nuclear medicine imaging, particularly for tomographic reconstruction. The scientific building blocks that were necessary for the structure of PET were contributed over a period of several decades by many investigators in physics, mathematics, chemistry, and fundamental biology. PMID- 1523413 TI - Cyclotrons and positron emission tomography radiopharmaceuticals for clinical imaging. AB - Positron emission tomography (PET) requires positron-emitting radionuclides that emit 511-keV photons detectable by PET imagers. Positron-emitting radionuclides are commonly produced in charged particle accelerators, eg, linear accelerators or cyclotrons. The most widely available radiopharmaceuticals for PET imaging are carbon-11-, nitrogen-13-, and oxygen-15-labeled compounds, many of which, either in their normal state or incorporated in other compounds, serve as physiological tracers. Other useful PET radiopharmaceuticals include fluorine-18-, bromine-75-, gallium-68 (68Ga)-, rubidium-82 (82Rb)-, and copper-62 (62Cu)-labeled compounds. Many positron emitters have short half-lives and thus require on-site cyclotrons for application, and others (68Ga, 82Rb, and 62Cu) are available from radionuclides generators using relatively long-lived parent radionuclides. This review is divided into two sections: cyclotrons and PET radiopharmaceuticals for clinical imaging. In the cyclotron section, the principle of operation of the cyclotron, types of cyclotrons, medical cyclotrons, and production of radionuclides are discussed. In the section on PET radiopharmaceuticals, the synthesis and clinical use of PET radiopharmaceuticals are described. PMID- 1523414 TI - Instrumentation for positron emission tomography: tomographs and data processing and display systems. AB - The field of positron emission tomography (PET) has evolved over the past 10 to 15 years from a basic research endeavor to a field in which both research and clinical studies are performed at over 100 institutions and medical facilities throughout the world. Most centers now use tomographs supplied by commercial vendors and operate data analysis systems employing identical software packages. PET scanners have advanced from prototypes assembled more than 15 years ago that imaged a single slice with 32 detectors at a resolution of greater than 2.0 cm full-width-at-half-maximum (FWHM), to current state-of-the-art instruments that simultaneously image as many as 47 slices using nearly 10,000 detector crystals at resolutions of less than 5 mm FWHM. In addition, specialized research instruments have been developed that have in-plane image resolution of approximately 2.5 mm FWHM. Other PET instrumentation advances include the development of detector block designs with multiple crystals per photomultiplier tube, continuous large position-sensing detectors, and the use of new detector materials having properties particularly suited for PET imaging. Image display and analysis systems have also advanced considerably over this time period. Early scanners typically used analysis stations with dedicated displays of only approximately 256 x 256 pixels and minimal internal processing capabilities. Current systems now offer displays with more than a megabyte (1,024 x 1,024) of image memory and have considerable internal processing capability. Further improvements in the ability to efficiently handle the massive volumes of data generated by the latest generation of scanners in increasingly sophisticated manners are crucial to the continued advancement of the PET field. PMID- 1523415 TI - Considerations in setting up a positron emission tomography center. AB - Clinically oriented imaging with position emission tomography (PET) has come of age. Given an adequate referral base and physician interest, a compelling argument can be made at all levels of the review process for setting up a PET program in a clinical setting. PET is expensive. It is obvious that the cost of running a PET service depends heavily on an institution's ability to obtain reasonable financing. Educational institutions have the opportunity to acquire special funding through a variety of sources. On the other hand, money can be expensive for private entrepreneurs. It appears that in the near future PET centers will probably remain at educational institutions or large well-financed community hospitals able to raise money at reasonable rates until reimbursement issues are better resolved. Finally, the future of clinical PET may hinge significantly on the ability of commercial radiopharmaceutical suppliers to provide regional fluorodeoxyglucose distribution. As an institutional program development, PET offers opportunities by providing unique clinical data aiding the referral pattern. PET may serve as a magnet for recruitment in many areas and may promote interdisciplinary cooperation. A clinical PET center serves both as a model for future and more widespread use of PET and as a training ground for medical personnel. Finally, the unique capabilities of PET may facilitate grant opportunities. PMID- 1523416 TI - Positron emission tomography as a multi-institutional effort. AB - The consortium relationship at State University of New York at Buffalo School of Medicine and Biomedical Sciences have made it possible to establish in this community a multi-institutional effort to develop positron emission tomography (PET). The type of approach used and the modalities employed to generate community, university, and federal support are presented. The development of PET technology has led to a greater understanding between the various disciplines, and joint efforts have been made to establish pilot projects in a number of research protocols in the clinical applications that are currently available today. The consortium concept has led to early consideration by third-party carriers to consider reimbursement for those established PET procedures that can be applied clinically. Hopefully, with the passage of time and the maturation of a regional PET center, the concepts proposed might be used as models for other installations throughout the country. PMID- 1523417 TI - The future of positron emission tomography in clinical medicine and the impact of drug regulation. AB - Positron emission tomography (PET) was initially developed as a research tool for evaluating normal and abnormal physiology. Subsequently, the potential clinical utility of PET was recognized, and several specific clinical indications have been defined. PET has been demonstrated to be clinically useful in evaluating certain disorders of the brain and heart. PET holds significant promise for use in the evaluation of psychiatric illness and in multiple aspects of evaluation of malignancy. A major limiting factor for the growth of clinical PET is the absence of policies for reimbursement by third-party payers. Although rubidium-82 chloride is approved by the Food and Drug Administration (FDA), the lack of FDA approval of fluorine-18 2-fluoro-2-deoxyglucose (FDG) is hampering reimbursement for PET studies. The jurisdiction of the FDA over cyclotron-produced PET radiopharmaceuticals synthesized and used on site is a matter of debate because these drugs are not introduced into interstate commerce and because these activities appear to be permissible under certain exemptions in the Federal Food, Drug, and Cosmetic Act relating to the practices of medicine and pharmacy. The jurisdictional authority of the FDA in regulating these radiopharmaceuticals would be established with certainty only through litigation, but no individual or organization has elected to challenge the FDA at this time. The Institute for Clinical PET (ICP) is developing a Drug Master File that can be used in support of site-specific New Drug Applications (NDAs) for cyclotron-produced radiopharmaceuticals by any organization desiring an NDA. The ICP is optimistic that this method of obtaining FDA-approval of FDG and other cyclotron-produced PET radiopharmaceuticals will be successful and beneficial to sites using PET clinically. PMID- 1523418 TI - Liver uptake of technetium-99m-labeled phosphate compounds: an updated gamut, 1992. PMID- 1523419 TI - Increased pulmonary radiothallium uptake during stress thallium-201 chloride myocardial imaging. PMID- 1523420 TI - Behavioral states and their ontogeny: human studies. PMID- 1523421 TI - Behavioral states and their ontogeny: animal studies. AB - Despite numerous attempts in describing the many underlying events correlated with changes in behavioral states, the biological significance of state alternation remains unknown. There does not yet exist a satisfactory explanation for the biological need for such state changes, nor does there exist sufficient physiological evidence to explain the underlying processes leading to these state transitions. Nonetheless, the study of these ontogeny of behavioral states is important because it shows the progressive ability of the organism to integrate multiple neuronal systems. Available literature suggests that some rudimentary form of behavioral state is established in fetal life throughout the animal kingdom, although there is substantial difference in the degree and rate of development of organized behavioral states among the different animal species. Highly organized behavioral states that involve concurrence of many physiologic systems are present in the third trimester in the fetal lamb, while they are not seen until 2 to 3 weeks postnatally in the rat, rabbit, and cat. Subsequent maturation consists primarily of increased cycle length in all species. In addition, there is some evidence that a circadian rhythm may be superimposed on the ultradian rhythm of behavioral states in immature animals, but there is currently no information on the ontogenesis of this circadian rhythm. It is currently hypothesized that behavioral states cycling in the adult is generated by the interaction of multiple, anatomically distributed sets of neurons. Electrophysiological and pharmacological studies have suggested that both the cholinergic and aminergic neuronal systems play important roles in the maintenance of state cycling. Studies in the fetal lamb also support these proposed mechanisms in early development.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1523422 TI - Behavioral states and the peripartum period. AB - Fetal movements with their associated FHR accelerations, as well as the cyclic alternation between episodes of low and high FHR variability, particularly in late pregnancy, give a clear indication of the fetal rest-activity cycle. FHR variability changes during labor indicate that the rest-activity cycle continues even though perceived movements may diminish and fetal breathing may stop. Fetal behavioral states, known to be present by term and characterized by the concordant association of fetal movements, continue during labor. However, not all labors show evidence of fetal behavior despite a normal outcome, and the significance of this remains unknown. The influence of the fetal rest-activity cycle on FHR variability is such that recognition of behavioral cycles, when present, is essential for appropriate interpretation of the FHR during labor. PMID- 1523423 TI - Fetal behavioral state and the cardiovascular system. PMID- 1523424 TI - The effect of behavioral state on fetal metabolism and blood flow circulation. AB - As in postnatal life, behavioral states when evident in utero are also seen to influence the metabolic activity and/or circulation of several organ systems if not the global metabolic and circulatory activity of the fetus. In some instances this effect is organ specific as in the increased metabolic activity of the brain during the fetal REM state, which may account for the prominence of this state through the perinatal period and contribute to the brain's growth and development at this time. Generalized metabolic and circulatory effects may also be seen as associated with state-related changes in fetal biophysical activity or circulating vasoactive substances. Although the exact functions of sleep and sleep states are not yet known, their influence on the metabolic and circulatory activity of organ systems is seen to onset in early life, suggesting that a need for such may be just as important during early development as in later life. PMID- 1523425 TI - Fetal behavioral states: biological alteration. PMID- 1523426 TI - Fetal behavioral states: pathological alterations with drug/alcohol abuse. PMID- 1523427 TI - Fetal behavioral states: pathological alteration with hypoxia. PMID- 1523428 TI - The organization of behavioral states and their dysfunction. PMID- 1523429 TI - Computed tomography of talocalcaneal coalition: imaging techniques. AB - The diagnosis of symptomatic talocalcaneal coalition requires an imaging study that demonstrates precise anatomic detail. Computed tomography affords the best method for the diagnosis. This essay reviews the computed tomographic anatomy of talocalcaneal coalitions in several projections and stresses the routine use of the angled coronal and direct sagittal projections. PMID- 1523430 TI - Value of polydirectional tomography in the assessment of the postoperative spine after anterior decompression and vertebral body autografting. AB - With the growing number of orthopedic reconstructive spinal procedures, the use of bone grafting has steadily increased in the past decade. An understanding of the biology of bone grafting is essential for both the clinician and radiologist. Despite the advent of computed tomography and magnetic resonance imaging, conventional polydirectional tomography remains an important tool in the evaluation of vertebral body autografts. Trispiral or hypocycloidal tomography plays a valuable role in the assessment of bone graft fusion and possible complications, especially in the presence of metallic fixation devices. We present our imaging experience derived from 375 patients with cervical, thoracic, or lumbar anterior spinal fusion. True graft complications occurred in 27 patients (7%) and consisted of fracture (4%), malpositioning (3%), and infection (less than 1%). PMID- 1523431 TI - The prevalence and significance of cyst-like changes at the cruciate ligament attachments in the knee. AB - Approximately 1% of the total population referred for magnetic resonance imaging (MRI) of the knee at our facility have cystic changes at or near the attachment of the anterior or posterior cruciate ligaments (ACL, PCL). Cases were collected prospectively from a group of 1710 consecutive knee MR examinations, and a retrospective study analyzed the typical appearance of these cysts and any associated findings. Although most of the cysts were an incidental finding, two were associated with significant adjacent marrow edema. PMID- 1523432 TI - The metacarpal index--obsolete in Marfan syndrome! AB - 28 patients with definite, probable or phenotypic Marfan syndrome underwent manual and computerised measurement of their metacarpal indices. Two methods were used from among the several variations quoted in the literature, one involving the average length/width of metacarpals 2-5 (method I), and the other dividing the sum of the lengths by the sum of the widths of these metacarpals (method II). The two methods are not mathematically identical, and a statistically significant difference was noted between them. Only 50% of the children in each group had elevated metacarpal indices, making it a time-consuming method that is indicative only of the phenotype and can be found in normal individuals. It should therefore be considered an obsolete measurement in Marfan syndrome. PMID- 1523433 TI - Contrast-enhanced fat saturation magnetic resonance imaging for studying the pathophysiology of osteonecrosis of the hips. AB - We imaged 75 hips in 40 patients using fat saturation technique before and after intravenous injection of contrast (0.1 mmol/kg gadolinium diethylene triamine penta-acetic acid, Gd-DTPA). Eighteen hips in 11 patients were determined to be osteonecrotic, either by pathologic or clinical examination. In the osteonecrotic hips, three distinct patterns of enhancement were found: (I) focal area outlined by brightly enhancing rim (7 hips); (II) diffuse enhancement in the femoral head and neck extending into the femoral shaft (3 hips); and (III) a combination of patterns I and II (8 hips). Our data support the hypothesis that early nontraumatic osteonecrosis is associated with hyperemia and/or an increase in capillary permeability rather than acute devascularization, and that diffuse marrow edema is the initial finding in early nontraumatic osteonecrosis. PMID- 1523434 TI - The skeleton in congenital, generalized lipodystrophy: evaluation using whole body radiographic surveys, magnetic resonance imaging and technetium-99m bone scintigraphy. AB - Congenital generalized lipodystrophy (CGL) is a rare genetic disease characterized by the absence of body fat from birth. Focal bone lesions have also been reported, but their pathophysiology is poorly understood. To characterize skeletal abnormalities further in 3 patients with CGL, we employed whole-body radiographic skeletal surveys, magnetic resonance imaging (MRI, including gadolinium enhancement), and triple phase technetium-99m methylene diphosphonate bone scintigraphy. Radiographs showed numerous focal lesions within the long bones, as described in other reports. MRI showed that the entire marrow space of the long bones was abnormal and was characterized, at least in part, by the absence of marrow fat. Prolonged T1 and T2 times and marked gadolinium enhancement were observed in radiographically normal-appearing long bone. Radiographically lytic lesions occasionally demonstrated fluid-fluid levels on MRI and enhanced peripherally after gadolinium infusion. Bone scintigraphy findings such as periarticular hyperemia were relative subtle. We conclude that the appendicular skeleton of patients with CGL is diffusely abnormal and is predisposed to focal osteolysis and cyst formation. PMID- 1523435 TI - Case report 728: Desmoplastic fibroma. AB - A 69-year-old woman with a 25-year history of recurrent sciatica presented with an expanding lytic lesion of the right side of the first sacral vertebra. Histological examination proved the lesion to be a DF. DF is usually diagnosed in young patients and is very rarely located in the spine and sacrum. The growth rate of the tumor was presumed to be very low because it had not progressed from radiological studies performed 9 years previously. The clinical, radiological, and pathological features of DF are described, and the differential diagnoses are discussed. The most difficult problem is to distinguish DF from a low-grade fibrosarcoma or chordoma. PMID- 1523437 TI - Case report 746: Osteopetrosis. AB - Osteoporosis is a disorder characterized by osteoclastic dysfunction. The bones of afflicted patients become sclerotic and show modeling defects resulting in either a decrease or obliteration of the marrow cavity and resultant pancytopenia. Other clinical manifestations include bony deformities, cranial nerve palsies from bony overgrowth, pathological fractures, osteomyelitis, and hepatosplenomegaly secondary to extramedullary hematopoiesis. In the skull, the diploic space is usually decreased or obliterated. Absent or decreased marrow space is observed on plain films. On MRI, the marrow cavity very likely will be obliterated with low signal intensity on T1- and T2-weighted images. We report a case of osteopetrosis in which the diploic space is markedly increased, giving a hair-on-end appearance resembling thalassemia major. Perhaps some local factor within the diploic space prevented the expected osteoclastic dysfunction, allowing remodeling and expansion of the cranial vault. PMID- 1523436 TI - Case report 745: Synovial lipoma arborescens. AB - A case is presented of lipoma arborescens of the knee with an atypical, sudden onset. Arthrography and ultrasound confirmed a synovially based lesion in the suprapatellar pouch. CT enabled a preoperative diagnosis of lipoma arborescens to be made, which was confirmed by surgical excision of a fronded fatty mass. Histological studies showed hyperplastic villi with mature adipose cells in the subsynovial layer. Resection of the synovium is considered curative, with only one case of recurrence after synovectomy having been reported [4]. PMID- 1523438 TI - Case report 747: Leiomyosarcoma of great saphenous vein. AB - Vena caval leiomyosarcomas are rare tumors; noncaval leiomyosarcomas are even less common and are rarely diagnosed preoperatively. We present a case of leiomyosarcoma of the great saphenous vein that was diagnosed by MRI based on its appearance and location. The presence of an intraluminal tumor in a vein on MRI should suggest the diagnosis of leiomyosarcoma of the vein, allowing definitive operative excision. With widespread use of MRI for indeterminate soft-tissue masses, we anticipate presurgical diagnosis of venous leiomyosarcoma will be made with increasing certainty and frequency. PMID- 1523439 TI - Case report 748: Chondroblastoma of the femur with an aneurysmal bone cyst. AB - A case of chondroblastoma associated with an aneurysmal bone cyst has been described. The radiographic appearance of the lesion understandably reflects the combined features of both tumors. Up to one-half of all cases of aneurysmal bone cysts are found in association with other tumors, benign or malignant, and up to 15% of chondroblastomas are combined with an aneurysmal bone cyst (4). PMID- 1523440 TI - Case report 750: Aspergillosis of the chest wall in an apparently immunocompetent host. AB - This is a case of aspergillosis of the bone and soft tissues of the chest wall in a (probably) immunocompetent host. The areas of involvement and different types of this disease are described. The A. flavus group, which presumably was responsible for this involvement of the chest wall, is very uncommon as a pathogen in humans. PMID- 1523441 TI - Case report 751: Spindle cell lipoma causing marked bone erosion. AB - We present an unusual case of spindle cell lipoma of the foot which produced marked bone erosion. Spindle cell lipoma was initially described in the mid-1970s as having the characteristics of a lipoma with partial or total replacement of mature fat by collagen-forming spindle cells. This lesion is most commonly found in the subcutaneous tissue of the posterior neck and shoulder in men between 45 and 65 years of age. PMID- 1523442 TI - Case report 752: Normal variant of the acromion simulating grade I acromioclavicular separation. AB - This case illustrates a developmental variant of the acromion resulting in apparent widening of the acromioclavicular joint space rather than discontinuity of the inferior cortices of the acromioclavicular joint. Had an axillary view not been obtained, an erroneous radiographic diagnosis of grade I acromioclavicular separation might have been suggested. PMID- 1523443 TI - On being politically correct. PMID- 1523444 TI - Who will heal the healers? PMID- 1523445 TI - Dysplastic (atypical) nevi: significance and management. AB - The frequency of malignant melanoma is rising at an alarming rate. Familial dysplastic nevi have been shown to be markers for and perhaps even precursors of malignant melanoma. This paper addresses the clinical and histologic features of these lesions, the structural and functional abnormalities of the melanocytes present in dysplastic nevi, the systemic and genetic abnormalities seen in patients with the dysplastic nevus syndrome, and the risk of melanoma in persons with dysplastic nevi. Management of persons with dysplastic nevi should include stressing sunlight avoidance and self-examination, deciding which lesion(s) to surgically excise, a schedule of visits to the physician, the possible use of photography, and the need to individualize patient management. PMID- 1523446 TI - Eosinophilia-myalgia syndrome: the aftermath. AB - We report here the long-term sequelae in 22 patients with L-tryptophan-induced eosinophilia-myalgia syndrome (EMS). The mean follow-up was 23 months (range, 5 to 40 months). Myalgia, rash, pruritus, edema, and respiratory symptoms often improved with the use of corticosteroids, but fatigue and weakness persisted in most cases. Other abnormalities that commonly persisted were arthralgia, muscle cramping, peripheral neuropathy, and thickened skin. One patient had chronic pulmonary hypertension. These findings indicate that for most patients, EMS is a chronic disorder. PMID- 1523447 TI - Infiltration during intravenous therapy in neonates: comparison of Teflon and Vialon catheters. AB - Infiltration is a frequent complication of intravenous therapy using peripheral venous lines in neonatal patients. In a randomized trial of two catheter materials, Vialon (Becton Dickinson) and Teflon (DuPont), we studied 19 putative risk factors for infiltration, including 11 infusates, in 772 peripheral venous lines in patients aged 1 to 67 days. The best-fit Cox regression model identified six significant predictors of infiltration (P less than .05): catheter material, age, anatomic insertion site, hyperalimentation, and use of furosemide and dopamine. For the subsample of patients weighing less than or equal to 1500 g, a second Cox regression model identified time spent inserting the catheter and the number of insertion attempts as additional significant predictors. These multivariate models showed that Vialon catheter material reduced the risk of infiltration by 18% (95% CI, 1% to 32% reduction) in the total sample and by 35% (95% CI, 15% to 50% reduction) in the higher risk low-weight (less than or equal to 1500 g) subsample. PMID- 1523448 TI - Single lung transplantation: replacement therapy for end-stage lung disease. AB - Advances in immunosuppression and operative techniques have allowed single lung transplantation to become a viable treatment option at selected medical centers. We describe eight patients, all from the southeastern United States, who had single lung transplantation at Vanderbilt University Medical Center from March 1990 to June 1991. Their diagnoses represent a diverse set of diseases including idiopathic pulmonary fibrosis, primary pulmonary hypertension, emphysema, and pulmonary veno-occlusive disease. After thorough evaluation, the average waiting period to transplantation was 165 days. The posttransplantation periods were conspicuous for rejection, infection, and other complications. All of these recipients have either returned to an active life or are actively recuperating; this center's first single lung recipient has now survived 15 months. Our initial experience with single lung transplantation is encouraging, yet broader application requires that the paucity of donor organ availability be rectified. PMID- 1523449 TI - Prevalence of olfactory dysfunction, hearing deficit, and cognitive dysfunction among elderly patients in a suburban family practice. AB - Olfactory and hearing senses diminish with age, and cognitive dysfunction increases. The association between sensory deficits and cognitive dysfunction has not been well studied. This paper presents the results of testing a group of 50 community-dwelling patients of a family physician who developed a computer assisted comprehensive geriatric assessment program. Olfactory dysfunction was present in 39% of subjects, with 18% being unable to detect smoke. There was no correlation between olfactory dysfunction and cognitive dysfunction. Hearing deficit, however, was found in 10% of subjects, all of whom also had either an associated olfactory or cognitive dysfunction. This study demonstrates the high prevalence of olfactory and auditory dysfunction in an ambulatory geriatric population, with a possible association between hearing deficit and cognitive dysfunction. The problem of multiple sensory deficits should be addressed in any long-term management decisions regarding elderly patients. PMID- 1523450 TI - Grip strength before and after carpal tunnel decompression. AB - We prospectively studied preoperative and postoperative grip and pinch strength in 21 patients having 30 consecutive median nerve decompressions for carpal tunnel syndrome. All procedures were done by one surgeon. Each hand operated on served as its own control and was studied by the same therapist preoperatively and at monthly intervals for 6 months after the procedure. An initial decline in both grip and pinch strength was noted in most hands during the first postoperative month. Eighty percent or more grip strength was regained in 65% of the hands at 2 months and in 81% at 3 or more months. In those hands (65%) that regained at least 100% of their preoperative grip strength at 3 or more months, there was an average increase in maximal grip of 56%, as compared with an average decrease of 20% in the remaining hands (35%). PMID- 1523451 TI - Infected pressure sores: comparison of methods for bacterial identification. AB - Diagnosis of the bacterial component of pressure sores is notoriously difficult. We comparatively studied three methods of specimen collection from 72 pressure sores. Specimens taken by swab or by needle aspiration were compared with deep biopsy specimens as to diagnostic reliability. We found that swab specimens reflected surface colonization and that needle aspiration seemed to underestimate bacterial isolates as compared with deep tissue biopsy specimens. We recommend that antibiotics not be routinely used for treatment of colonization in pressure sores; in patients with sepsis, deep biopsy specimens can accurately diagnose infection. PMID- 1523452 TI - Myasthenia gravis and HLA phenotypes in Jamaicans. AB - We determined HLA-antigen frequencies and corresponding relative risks (RR) in 30 Jamaicans with myasthenia gravis (MG) and 40 normal controls. Using a microcytotoxicity assay and commercially prepared typing trays, we found that the strongest HLA associations with MG in Jamaicans were with HLA-A2 (RR = 6.15), HLA B8 (RR = 3.4), HLA-B13 (RR = 7.76), and DQw4 (RR = 3.8). After correction of the P value for the number of antigens tested, only HLA-A2 was statistically significantly increased in MG patients. There was a statistically significant negative association between MG and HLA-DR2, as well as HLA-A9 and -B5. No correlation was observed between HLA phenotype, thymic disease, clinical grades, or disease course. HLA-A2 and sex were independent risk factors for MG, female patients having a higher risk (RR = 5.8). Further studies using larger patient and control groups, locally derived typing sera, and DNA probe analysis are indicated. PMID- 1523453 TI - Neuroanatomic/neuropathologic correlates in schizophrenia. AB - In the 1980s, numerous studies demonstrated neuropathologic changes in schizophrenia. Increased ventricle-brain ratios in schizophrenics have been reported. Birth-related trauma coupled with a genetic predisposition may be involved in the increased ventricle-brain ratios and in the development of some forms of the illness. Probable embryogenic anomalies in the hippocampus and other informational processing centers seem involved. PMID- 1523454 TI - Scientific and ethical considerations in human clinical experimentation. PMID- 1523455 TI - Cause or coincidence? PMID- 1523456 TI - Dr. William Thomas Watson: physician of the past. PMID- 1523457 TI - Infective endocarditis due to Neisseria sicca and associated with intravenous drug abuse. AB - Intravenous drug abusers are subject to infective endocarditis from unusual pathogens, including the saprophytic species of Neisseria, sometimes transmitted by needles contaminated with oral secretions. We have recently encountered such a case, in which a 37-year-old man with vegetations on the anterior leaflet of the tricuspid valve had blood cultures positive for N sicca. A history of intravenous drug abuse using needles contaminated with oral secretions should alert clinicians to the possibility of infective endocarditis due to saprophytic Neisseria species. PMID- 1523458 TI - Public health care: a prime solution. PMID- 1523459 TI - Dying professional courtesy. PMID- 1523460 TI - Tractor seat pressure sore. PMID- 1523461 TI - Malacological survey in the Bhumibol Reservoir, the first dam constructed in Thailand. AB - Twenty-five species of molluscs were found in a malacological survey in the Bhumibol Reservoir and in the Ping River in front of the Bhumibol Dam and its tributaries in April and August 1985. Among these species, Tricula aperta or Neotricula aperta, intermediate host of human schistosomes and Bithynia (Digoniostoma) siamensis goniomphalos and B. (D.) funiculata, the first intermediate host of human liver flukes, were not found. Although some of the intermediate hosts of mammalian schistosomes, Indoplanorbis exustus and Lymnaea (Radix) auricularia rubiginosa were found, none of them were positive for the parasitic infection. However, the malacological survey in the Bhumibol Reservoir revealed the existence of colonies of edible snails, Filopaludina (Filopaludina) doliaris, F. (F.) filosa and F. (Siamopaludina) martensi martensi along the shoreline of the reservoir. Thus, it is recommended that the local villagers collect them for household consumption or for sale. This practice would augment the food supply and also increase the income of the local villagers in the Bhumibol Reservoir area. PMID- 1523462 TI - Prevalence of anti-HCV antibody in family members of anti-HCV-positive patients with acute and chronic liver disease. AB - Presence of circulating anti-hepatitis C antibody (anti-HCV) was screened in 201 Thai patients with acute and chronic liver disease who presented to Ramathibodi and Phya Thai Hospitals during 1984-1990. Of these, 29 patients (14.4%) were positive for anti-HCV. Circulating anti-HCV was determined in 92 family members (20 spouses, 72 household contacts) of these index cases and was detected in 5 contacts (2 spouses, 2 daughters and 1 mother) of 3 index cases. The overall prevalence of anti-HCV among the contacts was 5.4% (5/92) and it was higher in sexual partners (2/20, 10.0%) compared to other household contacts (3/72, 4.2%) but this was not statistically significant (p = 0.297). The anti-HCV-positive contacts were significantly older (mean +/- SD = 61.4 +/- 14.4) than the other contacts either comparing within the same families (26 +/- 16.5; p = 0.012) or all studied families (25.1 +/- 13.3; p = 0.006). One anti-HCV-positive contact had hepatocellular carcinoma, one had unexplained elevation of serum aminotransferase and the remaining 3 had no clinical or laboratory evidence of liver disease. All of the 3 index cases with anti-HCV-positive contacts, had chronic liver disease (2 cirrhosis, 1 chronic persistent hepatitis) and the prevalence of anti-HCV in these families (8/13, 61.5%) was significantly higher than the remaining 26 families (26/108, 24.1%) (p = 0.008). The results of this study suggest that sexual and other intrafamilial personal contact may be important for HCV transmission. Duration of close contact and family relationships appear to determine this mode of HCV transmission. PMID- 1523463 TI - Adult longevity of certain mosquito species after larval and pupal exposure to sublethal concentration of an insect growth regulator, hexaflumuron. AB - Longevity of the adults of three vector species, Culex quinquefasciatus, Anopheles stephensi, and Aedes aegypti was drastically reduced when they were exposed at larval and pupal stages to sublethal concentrations of an insect growth regulator hexaflumuron. When the three species were exposed to 0.05 mg/l at the pupal stage, males and females of Cx. quinquefasciatus suffered a more shortened life span than other species. Among the females whose feeding activity was adversely affected by IGR treatment at the pupal stage, Ae. aegypti showed the minimum survival duration with LT50 of 2.74 days. PMID- 1523464 TI - Laboratory evaluation of five pesticides for control of Leptotrombidium fletcheri (Acari: Trombiculidae). AB - Five pesticides were evaluated against laboratory colonies of Leptotrombidium fletcheri (Womersly and Heaslip) by the Pasteur pipet technique. The pesticides were dieldrin (LC50 = 3.6 ppm, LC99 = 18.2 ppm), bromopropylate (LC50 = 9.2 ppm, LC99 = 239.6 ppm), dicofol (LC50 = 27.8 ppm, LC99 = 118.1 ppm), fenthion (LC50 = 15.4 ppm, LC99 = 29.7 ppm), and malathion (LC50 = 84.7 ppm, LC99 = 313.9 ppm). Dieldrin was the most toxic. Dicofol was recommended for further evaluation in field trials. PMID- 1523465 TI - Anopheles dirus size and fecundity: relationship to larval density and protein accumulation. AB - Anopheles dirus were reared at two different larval densities (100/pan and 400/pan) to produce two different size classes of adults. Both the wing length and fecundity of females from the two densities were significantly different (p less than 0.001). Adult size was related to larval density and protein accumulation during immature life. Egg production was also related to adult size. Consequently, larger field adults have the potential to live longer and produce more eggs. The smaller adult size associated with crowded larval development was apparently caused by space associated effect on feeding rather than by a shortage of food per se. PMID- 1523466 TI - Cryptosporidium in 100 Australian children. AB - Over a consecutive 36 month period, 100 patients out of 6,980 (1.4%) from whom stool samples were examined had oocysts of Cryptosporidium detected on fecal microscopy. Three patients were receiving cytotoxic chemotherapy and adequate clinical information was available from 84 of the remainder. Fifty per cent of patients were aged 1 to 2 years, 29% were less than 12 months and the rest were more than 2 years of age. More than one-quarter of the patients were Australian Aborigines. Isolations of cryptosporidia were most prevalent in late summer, autumn and early winter. Most patients (89%) had diarrhea, more than 75% had vomiting and 44% were dehydrated, mostly to a mild degree. Other symptoms included fever (11%) and abdominal pain (11%). Ten percent of patients were apparently symptomless. Cryptosporidium sp. is the second most commonly identified intestinal parasite, after Giardia intestinalis, in fecal specimens examined in our children's hospital. The high rate of isolation in Aboriginal children emphasized the importance of enteric pathogens in this group and the role of inadequate hygiene in relation to diarrheal disease in young Aborigines. PMID- 1523467 TI - Community-acquired pulmonary infection due to Chlamydia in tropical Queensland. AB - By using enzyme immunoassay and immunofluorescence antigen detection techniques on sputum specimens, four of 260 patients with pulmonary infection resident in tropical Queensland were found to be infected with Chlamydia. All four chlamydial infections were community-acquired and there was no history of close contact with birds by any of the four patients. One woman was deemed to be suffering with Chlamydia pneumonia, while the role of the organism in the pathogenesis of respiratory disease in the other three patients was indeterminate. At present, the incidence of pulmonary chlamydial infection in the population of tropical Queensland does not warrant routine testing, but investigations for these organisms should be undertaken in patients who present to their physicians with atypical pulmonary infection or whose clinical conditions are refractory to penicillin/ampicillin therapy. PMID- 1523468 TI - Prevalence of complement fixing antibody to Mycoplasma pneumoniae in Thai children. AB - The prevalence of antibodies to Mycoplasma pneumoniae was determined in normal Thai children by means of complement fixation. There were 445 children (243 boys and 202 girls) of different ages, ranging from newborn to 15 years. The lowest frequency of complement-fixing antibody was found in children age 1-3 months, and highest in children age 6-10 years which corresponds to the age distribution of symptomatic M. pneumoniae infection. The lowest and highest titers measured were less than 1:8 and 1:512 respectively. The prevalence of complement fixing antibody of titers more than or equal to 1:8, 1:32, 1:64 and 1:128 were 61.3, 31.7, 25.4 and 10.3 per cent of total children, respectively. Among children less than one month old, the frequency of complement fixing antibody of titers greater than or equal to 1:32 was 12.2 per cent and decreased to 1.3 per cent among children from the age 1-3 months. This decrease probably represented the disappearance of maternal antibody over this period. An increase in both the frequency and the geometric mean titer was seen thereafter. The peak frequency of high titers (greater than or equal to 1:32), 81.1 per cent, occurred in children 6-10 year of age. Paired sera were obtained from 72 children with high titers of greater than or equal to 1:64, 9.7 per cent had four fold changes of titer which indicated recent infection.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1523469 TI - Species-differences in the pH-activity pattern of acid phosphatase in the family Enterobacteriaceae. AB - Nonspecific phosphatase activities were surveyed comparing major species of the family Enterobacteriaceae. The strains were subjected to a whole cell assay system with paranitrophenyl phosphate as substrate over a wide pH range and with a standardized number of bacterial cells. The overall results suggest that the general shape of the pH activity curve and the location of peaks (pH optimum) can be employed as a supplementary criterion to characterize species of Enterobacteriaceae. PMID- 1523470 TI - Estimation of dengue infection attack rate in a cohort of children during a dengue 3 outbreak in Tahiti (1989-1990). PMID- 1523471 TI - Radix quadrasi and Physastra hungerfordiana: additional natural second intermediate hosts of Echinostoma malayanum in the Philippines. PMID- 1523472 TI - Parasitic contamination of selected vegetables sold in Metropolitan Manila, Philippines. PMID- 1523473 TI - Transient paralytic attacks with cerebral cysticercosis. PMID- 1523474 TI - Experimental infection of yellow tree monitor (Varanus bengalensis) and related species with Angiostrongylus cantonensis. PMID- 1523475 TI - Prevalence of varicella-zoster virus infection in Singapore. AB - The incidence of chickenpox in Singapore has been increasing since 1984. A seroepidemiological survey was conducted in 1989-90 to determine the prevalence of varicella-zoster virus-specific IgG antibody in the healthy population in Singapore aged from 6 months to over 45 years. Overall, 42.8% of 500 samples assayed qualitatively by the ELISA method were positive, with less than one fifth of those aged under 15 years and less than half of the 15-24 year olds possessing antibody to the virus. However, antibody prevalence increased markedly to between 86% and 98% in those over 25 years of age. No significant sex or ethnic difference was noted. The survey confirmed the low herd immunity and the higher susceptibility of the young adult population to varicella infection in a tropical city compared to that of temperate countries. PMID- 1523476 TI - Infants born to HIV infected mothers. AB - Eighty infants born to HIV-infected mothers were studied prospectively at Children's Hospital, Bangkok, Thailand from February 1989 to June 1991. The risk factors for acquisition of HIV infection were analyzed in 33 mothers (41.25%) including a history of being sex workers and having husbands who had extramarital sexual contact (22.5% each), having other sexually transmitted diseases (20.0%) and being IV drug users (6.25%). All infants appeared clinically normal without congenital anomaly, 22.5% (18 of 80) were of low birth weight with 91.43% (64 of 70) positive for HIV-antibody at birth. On follow up 56.25% (9 of 16) seroreversed during age 6 to 15 months, whereas 5 infants who were HIV-Ab negative at birth remained Ab negative on follow up for up to 15 months. One of 49 infants who attended the follow up clinic had been suffering from recurrent diarrhea, failure to thrive and encephalopathy since 9 months old; she weighed 6.7 kg at 15 months of age and remained positive for HIV-Ab. PMID- 1523477 TI - Thrombocytopenia in malaria. AB - The relationship between platelet counts and platelet bound (direct) or platelet directed (indirect) serum antibody concentrations was studied in 17 patients with Plasmodium falciparum malaria and 12 patients with P. vivax malaria. Platelet counts rose with recovery from infection from 196 +/- 84 x 10(9)/l (mean +/- SD) and 195 +/- 34 x 10(9)/l to 319 +/- 99 and 283 +/- 62 x 10(9)/l respectively (p less than 0.002), but there was no relationship between either absolute platelet count or changes in counts and either indirect or direct platelet antibody levels. These findings suggest that a non-immunologically mediated mechanism is involved in the pathogenesis of thrombocytopenia in malaria. PMID- 1523478 TI - Effect of mefloquine on electrocardiographic changes in uncomplicated falciparum malaria patients. AB - Asymptomatic sinus bradycardia and sinus arrhythmia have been noted in malarial patients receiving mefloquine. The present study was designed to assess the effect of mefloquine on electrocardiogram in malarial patients. The study was carried out in 102 acute uncomplicated falciparum malarial patients who were treated with mefloquine 750 mg and 1,250 mg regimens and 18 healthy male volunteers receiving 750 mg of mefloquine. Electrocardiogram was performed at intervals after mefloquine administration for a period of 42 days. PR, QRS, QT, QTc, RR interval and cardiac arrhythmia were measured and read by EKG-analyser with confirmation by a cardiologist. Sinus bradycardia and sinus arrhythmia were found in 61.8% and 45.1%, respectively during the first week after treatment. The patients' heart rate decreased significantly on day 6 after mefloquine administration when compared to day 0. The occurrence of sinus bradycardia and sinus arrhythmia were significantly higher in malarial patients when compared with findings in healthy subjects of the same age group. It is unlikely that these changes are associated with mefloquine concentration as mefloquine peaks around 12-24 hours after administration. There were no significant changes in PR interval, QRS-interval and QTc interval on the electrocardiogram. The findings in this study suggest that cardiotoxicity from mefloquine is unlikely. Bradycardia may be the result of autonomic control modulation after resolution of high fever. PMID- 1523479 TI - Comparative trial on the response of Plasmodium falciparum to halofantrine and mefloquine in Trat Province, eastern Thailand. AB - With the appearance of strains of Plasmodium falciparum in the Trat Province, eastern Thailand, reported to have developed resistance to mefloquine there is a need for an alternative drug. This comparative trial with mefloquine and halofantrine has demonstrated extremely low cure rates with both drugs (33.3% and 28.13% respectively), cross-resistance is suggested. PMID- 1523480 TI - Comparison of effects of pyronaridine, amodiaquine, mefloquine and qinghaosu on rodent malaria. AB - Blood schizontocidal effect of antimalarials were compared by 4-day suppressive test with an extended observation period of 31 days. On a drug-sensitive Plasmodium berghei ANKA strain, pyronaridine (PND) exhibited the best effect, followed by amodiaquine (ADQ), mefloquine (MFQ), and qinghaosu (QHS). On a moderately chloroquine-resistant P. berghei NS line, the order of effects was the same, PND greater than ADQ greater than MFQ greater than QHS. On a highly pyronaridine-resistant P. berghei RP line, ADQ, MFQ and QHS showed cross resistance with PND. PMID- 1523481 TI - Erythrocyte glucose-6-phosphate dehydrogenase and pyruvate kinase activities in hemoglobin H disease. AB - Erythrocyte glucose-6-phosphate dehydrogenase (G6PD) and pyruvate kinase (PK) activities were studied in hemoglobin H (HbH) patients by spectrophotometric method, cytochemical method and the methemoglobin reduction (MR) test for the detection of heterozygous G6PD deficiency. G6PD deficiency was found in 7 of 64 cases (10.9%), including 3 cases of genotype alpha 1/alpha 2 and 4 cases of genotype alpha 1/CS. None of the HbH patients was found to be PK-deficient. Spectrophotometrically determined G6PD and PK activities were significantly higher in HbH patients than in normals (p less than 0.001), whereas the MR test yielded a significantly lower percentage of residual methemoglobin in HbH patients than in normals (p less than 0.05). All three methods were efficient in the detection of hemizygous G6PD deficiency in HbH patients, but not in G6PD deficient females. PMID- 1523482 TI - Studies on the use of cobalt-60 gamma irradiation to control infectivity of Clonorchis sinensis metacercariae. AB - The purpose of the present study was to observe the survival and development of Clonorchis sinensis metacercariae in their final hosts after Cobalt-60 gamma irradiation of isolated metacercariae or the parasite in fish. Guinea pigs or albino rats were orally infected with irradiated metacercariae by gavage. Bioassay, fecal examination for ova, and necropsy of infected animals, were the methods used for the estimation of minimum effective dose of gamma irradiation to control infectivity of the metacercariae. Results showed that the minimum effective irradiation dose for isolated metacercariae was 0.05 kGy. The LD50 of the irradiation dose for metacercariae in fish was 0.05 kGy, and the minimum effective dose was 0.15 kGy. No significant difference in radiation susceptibility to Co-60 gamma irradiation was found among C. sinensis metacercariae in fishes collected at different localities in northern, middle or southern parts of China. The present finding suggests that irradiation of fish by 0.15 kGy could control infectivity of C. Sinensis metacercariae and thus be adopted as a control measure in preventing infections. PMID- 1523483 TI - Comparison of cysticercus extract, cyst fluid and Taenia saginata extract for use in ELISA for serodiagnosis of neurocysticercosis. AB - Cysticercus cellulosae extract (CS), cyst fluid (CF), and an extract of Taenia saginata adult worm (TS) were evaluated for use in an enzyme-linked immunosorbent assay (ELISA) for serodiagnosis of human neurocysticercosis in Thai patients. ELISA sensitivity was found to be 78.13%, 81.25% and 62.50%, respectively. False positivity was 6.66% with CS and 0% with other antigens. CF gave positivity with a pooled visceral gnathostomiasis serum and 3 of 10 (30%) of angiostrongyliasis sera. CS produced weakly positive ELISA with pooled opisthorchiasis and visceral gnathostomiasis sera. TS gave weak positive ELISA with a pooled opisthorchiasis serum. It was concluded that CF was the best antigen for use in ELISA for serodiagnosis of human neurocysticercosis. PMID- 1523484 TI - Prevalence of Enterobius vermicularis amongst adults living in hostels by six successive day examination. AB - The prevalence of Enterobius vermicularis in four groups of adults, all trainee public health inspectors or public health nurses, aged 18-35 years and all living in hostels on campus was studied. The modified scotch tape technique was used and the subjects were taught to do the examination on themselves to detect the presence of eggs over a period of 6 successive mornings. Each was given an elaborately illustrated diagram on how and when to take the samples and given demonstration in groups. The samples were examined by trained people. Most of the subjects took samples on 6 consecutive days. Of the 119 subjects who returned samples, the overall prevalence of E. vermicularis was 9.2% and this was thought to be high for this particular age group. This was due to the higher prevalence (19.4%) in one group, whereas in the others the range was 3.5-8.0%. Based on the samples returned on the first day none of the subjects were detected as having the infection. After examination on 3 successive days (109 subjects) 10.1% were found to be infected (chi 2 = 10.704; d. f. = 1) and after examination on 6 successive days (72 subjects) 13.9% were found to be infected (chi 2 = 3.026; d. f. = 1). There was no significance between examination over 3 successive days and 6 consecutive days (chi 2 = 0.296; d. f. = 1). There was no difference in the prevalence between males and females.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1523486 TI - Induction of intestinal lesions in rabbits with Koyan and Baling strains of Schistosoma malayensis Sp N. AB - Schistosoma malayensis Sp N is a putative new species of schistosome discovered in Peninsular Malaysia in 1973. This paper comprises the first report on the detailed gastrointestinal pathology present in rabbits infected with strains of the parasite. Two different strains of schistosome--the Baling and Koyan strains- from two different ecosystems were used to infect inbred rabbits and the resulting pathophysiology was studied. Our results showed that the Baling strain of S. malayensis was more virulent than the Koyan strain and produced nodular, segmental circumferential lesions and large bilharziomas measuring 1-7 cm in diameter in the distal jejunum, ileum and the ileo-caecal junction. The findings indicate that the Baling strain of S. malayensis was more pathogenic for rabbits as compared with the Koyan strain--in relation to the gross pathology of the gut and the tissue egg load. Earlier reports have shown that rabbits infected with S. japonicum induces significant intestinal lesions in rabbits (Cheever et al, 1980 a,b) but these animals are refractory to infection with S. mekongi (Byram and Lichtenberg, 1980). Our studies show that the two strains of S. malayensis adapted well in rabbits. It is also established that in rabbits, the virulence of the Baling strain of S. malayensis is greater than that of S. mekongi and approximates that of S. japonicum. PMID- 1523485 TI - Diversity of complement-mediated immune reaction to Trypanosoma gambiense. AB - Intact and papain-treated Trypanosoma gambiense clone populations, each expressing special antigens on their cell surfaces, were mixed with rabbit antiserum in the presence of complement. Two distinct types of immune reaction between trypanosomes and antisera were observed: clumping followed by dissociation (CD) and inhibition of aggregation (IA). Special antigens on the cell surface of trypanosomes exposed after papain digestion are implicated in both types of immune reaction. IA was considered to be more effective as an immunological response which would allow the infected host to clear the pathogen without any obstruction of capillaries and impairment of blood flow caused by clumping masses of trypanosomes. PMID- 1523487 TI - Quantitative internal dens morphology. AB - Recent work has demonstrated the highly variable and unpredictable external dimensions of the dens (odontoid process). No data have been available regarding internal dimensions. Quantitative computed tomography analysis of 120 axis vertebrae allowed nondestructive measurement of external and internal dens dimensions. The external computed tomography measurements correlated well with caliper-derived data. Minimum internal dens dimensions and cortical thicknesses in the sagittal and transverse planes are reported. Some axis vertebrae may not be amenable to internal fixation of type II dens fractures. Preoperative planning should include quantitative computed tomography analysis of the dens.